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World Cancer Day is a campaign to promote global awareness of cancer and to encourage its prevention, detection, and treatment. The day was initiated by the Union for International Cancer Control (UICC) in 2000 serving as a platform to promote research, improve education, and increase funding for cancer treatment and care.

World Cancer Day 

Key Statistics: The Global Impact of Cancer

Cancer is one of the foremost causes of mortality around the globe. In 2022, there were nearly 20 million new cases, and 9.7 million deaths attributed to cancer worldwide. Projections indicate that by 2040, the annual number of new cancer cases could reach 29.9 million, with cancer-related deaths increasing to 15.3 million.

In general, cancer rates tend to be highest in countries where populations enjoy greater life expectancy, educational attainment, and living standards. However, certain types of cancer, such as cervical cancer, show a contrasting trend, with the highest incidence found in countries where these measures are lower (1, 2).

Discover BIOMEDICA´s Biomarker ELISA kits for cancer research

Neuropilin-1, Periostin, Semaphorin 4D, Osteoprotegerin, RANKL, LRG1,  and others

 

Advantages of Biomedica ELISA assay kits

• RELIABLE – full validation package
  • CONVENIENT – assay range optimized for clinical samples
  • EASY – ready to use prediluted calibrators & controls
  • LOW sample volumes
  • TRUSTED – widely cited

 

Literature

1. https://www.cancer.gov/about-cancer/understanding/statistics
2. Cancer statistics for the year 2020: An overview. Int J Cancer. Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, Bray F. 2021 Apr 5. doi: 10.1002/ijc.33588. Epub ahead of print. PMID: 33818764.

 

Further reading

Influence of Diet and Nutrition on Prostate Cancer. Matsushita M, Fujita K, Nonomura N. Int J Mol Sci. 2020 Feb 20;21(4):1447. doi: 10.3390/ijms21041447. PMID: 32093338; PMCID: PMC7073095.

Abstract

The incidence of prostate cancer (PCa) displays widespread regional differences, probably owing to differences in dietary habits. Nutrients, including fat, protein, carbohydrates, vitamins (vitamin A, D, and E), and polyphenols, potentially affect PCa pathogenesis and progression, as previously reported using animal models; however, clinical studies have reported controversial results for almost all nutrients. The effects of these nutrients may be manifested through various mechanisms including inflammation, antioxidant effects, and the action of sex hormones. Dietary patterns including the Western and Prudent patterns also influence the risk of PCa. Recent studies reported that the gut microbiota contribute to tumorigenesis in some organs. Diet composition and lifestyle have a direct and profound effect on the gut bacteria. Human studies reported an increase in the abundance of specific gut bacteria in PCa patients. Although there are few studies concerning their relationship, diet and nutrition could influence PCa, and this could be mediated by gut microbiota. An intervention of dietary patterns could contribute to the prevention of PCa. An intervention targeting dietary patterns may thus help prevent PCa.

Breast cancer: A review of risk factors and diagnosis. Medicine (Baltimore). Obeagu EI, Obeagu GU 2024 Jan 19;103(3):e36905. doi: 10.1097/MD.0000000000036905. PMID: 38241592; PMCID: PMC10798762.

Abstract

Breast cancer remains a complex and prevalent health concern affecting millions of individuals worldwide. This review paper presents a comprehensive analysis of the multifaceted landscape of breast cancer, elucidating the diverse spectrum of risk factors contributing to its occurrence and exploring advancements in diagnostic methodologies. Through an extensive examination of current literature, various risk factors have been identified, encompassing genetic predispositions such as BRCA mutations, hormonal influences, lifestyle factors, and reproductive patterns. Age, family history, and environmental factors further contribute to the intricate tapestry of breast cancer etiology. Moreover, this review delineates the pivotal role of diagnostic tools in the early detection and management of breast cancer. Mammography, the cornerstone of breast cancer screening, is augmented by emerging technologies like magnetic resonance imaging and molecular testing, enabling improved sensitivity and specificity in diagnosing breast malignancies. Despite these advancements, challenges persist in ensuring widespread accessibility to screening programs, particularly in resource-limited settings. In conclusion, this review underscores the importance of understanding diverse risk factors in the development of breast cancer and emphasizes the critical role of evolving diagnostic modalities in enhancing early detection. The synthesis of current knowledge in this review aims to contribute to a deeper comprehension of breast cancer’s multifactorial nature and inform future directions in research, screening strategies, and preventive interventions.

Sclerostin and Periostin associated with vascular risk scales in type 2 diabetes

Exciting research news! The BIOMEDICA bioactive Sclerostin and Periostin ELISA kits were used in a groundbreaking study evaluating the association of these bone proteins related to cardiovascular disease (CVD), with the main vascular risk scales in patients with type 2 diabetes.

All Biomedica ELISA assays are fully validated following international quality guidelines.

Bioactive Sclerostin ELISA (cat. no. BI-20472)

• CHARACTERIZED ANTIBODIES – targeting the receptor binding region
• LOW sample volume – 20µl sample /well 

 

Sclerostin ELISA (cat. no. BI-20492)

• TRUSTED – most referenced Sclerostin ELISA (+280 citations)
• LOW sample volume – 20µl sample /well

 

Periostin ELISA (cat. no. BI-20433)

• LOW sample volume – 20µl sample /well
• SPECIFIC – Characterized, epitope mapped capture and detection antibodies:

Characterization of a sandwich ELISA for the quantification of all human periostin isoforms. Gadermaier, E et al.

 

Sclerostin and Periostin associated with vascular risk scales in type 2 diabetes

Type 2 diabetes is linked to an elevated risk of cardiovascular disease (CVD), affecting approximately 35% of patients with the condition (1). As a result, assessing cardiovascular risk is essential for effective disease management in individuals with type 2 diabetes. Various risk scores have been developed to estimate CVD in the general population, including the Framingham Risk Score (FRS), the REGICOR and more recently, the SCORE2-Diabetes was introduced, specifically tailored for individuals with type 2 diabetes (2).

While these computational tools are utilized in clinical practice, there remains a need to investigate new biomarkers that could enhance cardiovascular risk stratification for patients with type 2 diabetes.

Typical bone proteins, including Sclerostin and Periostin, have been linked to cardiovascular disease (CVD). Concurrently, various risk scores have been created to forecast CVD in the general population. The objective of the following study was to examine the relationship between these bone proteins connected to CVD and key vascular risk scales:

Bone proteins are associated with cardiovascular risk according to the SCORE2-Diabetes algorithm. González-Salvatierra S et al., Cardiovasc Diabetol. 2024.  

Key findings:

• Sclerostin and Periostin are associated with vascular risk in the SCORE2-Diabetes algorithm.
• This suggests that Sclerostin and Periostin may serve as useful diagnostic biomarkers for vascular risk in patients with type 2 diabetes.
• Future prospective studies are needed to validate the significance of these bone proteins in assessing vascular risk in the diabetic population.

 

Abstract

Background: Typical bone proteins, such as sclerostin and periostin, have been associated with cardiovascular disease (CVD). Simultaneously, several risk scores have been developed to predict CVD in the general population. Therefore, we aimed to evaluate the association of these bone proteins related to CVD, with the main vascular risk scales: Framingham Risk Score (FRS), REGICOR and SCORE2-Diabetes, in patients with type 2 diabetes. We focus in particular on the SCORE2-Diabetes algorithm, which predicts 10-year CVD risk and is specific to the study population.

Methods: This was a cross-sectional study including 104 patients with type 2 diabetes (62 ± 6 years, 60% males). Clinical data, biochemical measurements, and serum bioactive sclerostin and periostin levels were collected, and different risk scales were calculated. The association between bioactive sclerostin or periostin with the risk scales was analyzed.

Results: A positive correlation was observed between circulating levels of bioactive sclerostin (p < 0.001) and periostin (p < 0.001) with SCORE2-Diabetes values. However, no correlation was found with FRS or REGICOR scales. Both serum bioactive sclerostin and periostin levels were significantly elevated in patients at high-very high risk of CVD (score ≥ 10%) than in the low-moderate risk group (score < 10%) (p < 0.001 for both). Moreover, analyzing these proteins to identify patients with type 2 diabetes at high-very high vascular risk using ROC curves, we observed significant AUC values for bioactive sclerostin (AUC = 0.696; p = 0.001), periostin (AUC = 0.749; p < 0.001), and the model combining both (AUC = 0.795; p < 0.001). For diagnosing high-very high vascular risk, serum bioactive sclerostin levels > 131 pmol/L showed 51.6% sensitivity and 78.6% specificity. Similarly, serum periostin levels > 1144 pmol/L had 64.5% sensitivity and 76.2% specificity.

Conclusions: Sclerostin and periostin are associated with vascular risk in the SCORE2-Diabetes algorithm, opening a new line of investigation to identify novel biomarkers of cardiovascular risk in the type 2 diabetes population.

 

Literature

1. Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management. Ma CX, Ma XN, Guan CH, Li YD, Mauricio D, Fu SB. Cardiovasc Diabetol. 2022 May 14;21(1):74. doi: 10.1186/s12933-022-01516-6. PMID: 35568946.
2. Bone proteins are associated with cardiovascular risk according to the SCORE2-Diabetes algorithm. González-Salvatierra S, García-Martín A, García-Fontana B, Martínez-Heredia L, García-Fontana C, Muñoz-Torres M. Cardiovasc Diabetol. 2024 Aug 24;23(1):311. doi: 10.1186/s12933-024-02406-9. PMID: 39182106.

 

 

Heart failure (HF) is a clinical condition caused by structural and/or functional abnormalities of the heart. Increased filling pressure in the heart´s left ventricle (LV) indicates diastolic dysfunction. The golden standard for diagnosis is the measurement of LV end-diastolic pressure (LVEDP) obtained through cardiac catheterization. However, this procedure is invasive. The objective of the following study was to explore the relationship between LVEDP and cardiac serum biomarkers, including including N-terminal prohormone B-type natriuretic peptide (NT-proBNP) and soluble ST2.

Natriuretic peptides and soluble ST2 improves echocardiographic diagnosis of elevated left ventricular filling pressures. Călburean Paet al., Sci Rep. 2024 Sep 27;14(1):22171. doi: 10.1038/s41598-024-73349-0. PMID: 39333652; PMCID: PMC11436802.

 

Abstract

Elevated filling pressure of the left ventricle (LV) defines diastolic dysfunction. The gold standard for diagnosis is represented by the measurement of LV end-diastolic pressure (LVEDP) during cardiac catheterization, but it has the disadvantage of being an invasive procedure. This study aimed to investigate the correlation between LVEDP and cardiac serum biomarkers such as natriuretic peptides (mid-regional pro-atrial natriuretic peptide [MR-proANP], B-type natriuretic peptide [BNP], and N-terminal prohormone BNP [NT-proBNP]), soluble ST2 (sST2), galectin-3 and mid-regional pro-adrenomedullin (MR-proAMD). Consecutive patients hospitalized in a tertiary center and undergoing left cardiac catheterization were included in the study. Diastolic dysfunction was considered present if the end-expiratory LVEDP was ≥ 15 mmHg. Cardiac biomarkers were determined from pre-procedural peripheral venous blood samples. A total of 110 patients were included, of whom 76 (69.0%) were males, with a median age of 65 (55-71) years. Median LVEDP was 13.5 (8-19) mmHg and diastolic dysfunction was present in 50 (45.4%) of the patients. LVEDP correlated with BNP (p < 0.0001, r = 0.39 [0.20-0.53]), NT-proBNP (p < 0.0001, r = 0.40 [0.22-0.55]), MR-proANP (p = 0.001, r = 0.30 [0.11-0.46]), sST2 (p < 0.0001, r = 0.47 [0.30-0.60]), but not with MR-proAMD (p = 0.77) or galectin-3 (p = 0.76). In the final stepwise multivariable binary logistic regression model, diastolic dysfunction was predicted by NT-proBNP, mitral average E/e’, sST2, atrial fibrillation, and left atrium reservoir strain. BNP, NT-proBNP, MR-proANP, and sST2 had predictive value for diastolic dysfunction. In contrast, galectin-3 and MR-proAMD were not associated with increased filling pressures. Furthermore, NT-proBNP and sST2 significantly improved diastolic dysfunction prediction in the final multivariable mode.

Diagnosis of Diastolic Heart Failure with NT-proBNP

NT-proBNP ELISA (cat. no. SK-1204)

√  CONVENIENT – can be used in every lab
√  RELIABLE – Full validation package
√  CE registered – for IVD use in EU
√  Widely cited in more than 130 publications 

 

 

Quantification and Clinical Relevance of Oxidized Low-Density Lipoprotein (oLAb) Antibodies

Oxidized LDL contains a vast and currently unknown variety of epitopes that trigger the production of antibodies against these molecules (1). Since the mid-1990s, we at BIOMEDICA have been a leader in developing the “oLAb” ELISA assay, designed to measure IgG antibodies to oxidized LDL, based on the research of Tatzber and Esterbauer from 1995 (2). Utilizing this methodology, numerous studies have been conducted over the past several decades, yielding insights into the immunological aspects of oxidative stress in various diseases, contributing to advancements in medicine and human health (1-5).  Oxidized LDL antibodies (oLAb) have been regarded as indicators of the immune response to the oxidation of low density lipoprotein (oxLDL). Investigators have discussed that measuring oxLDL antibodies might provide a more accurate reflection of oxidative stress levels than measuring oxidized LDL itself (6).

More about Oxidative Stress and Oxidized Low-Density Lipoprotein (oLAb) Antibodies

Oxidative Stress is an imbalance between reactive oxygen species (ROS) production and the body’s ability to neutralize them, leading to cellular damage. It arises from both internal (e.g., mitochondrial respiration, metabolic processes) and external (e.g., pollution, UV radiation, poor diet) sources. The consequences include cellular damage, inflammation, and aging, contributing to diseases like cardiovascular illness, cancer, neurodegenerative disorders, and diabetes. The body employs enzymatic (e.g., superoxide dismutase, catalase) and non-enzymatic (e.g., vitamins C and E, glutathione) antioxidants to combat oxidative stress, which is crucial for maintaining health.

Autoantibodies against Oxidized LDL are antibodies produced by the immune system that specifically target oxidized low-density lipoprotein (LDL). Oxidized LDL plays a significant role in atherosclerosis and cardiovascular diseases, as it contributes to the formation of fatty plaques in arteries. The presence of these autoantibodies can indicate an autoimmune response and may serve as a biomarker for cardiovascular risk. They can also have protective or detrimental effects, depending on their concentration and context, influencing lipid metabolism and inflammation. Understanding these autoantibodies is crucial for developing potential diagnostic and therapeutic strategies in cardiovascular disease management.

Oxidized Low-Density Lipoprotein (oLAb) Antibodies

Autoantibodies targeting oxidatively modified LDL particles can easily be measured in serum with a commercial and standardized ELISA assay.

Anti-Oxidized LDL Antibody ELISA (oLAB) Assay (cat. no. BI-20032)

Features

• Standardized method with over 30 years’ experience in oLAB ELISA production
• Widely referenced

• Results in 2,5 hours
• 2 controls included

 

 

Conclusion

Over the last thirty years, the clinical significance and understanding of antibodies against oxidized low-density lipoproteins has evolved, offering valuable insights into their impact on cardiovascular health and disease. Progress in ELISA technology has been crucial for this research, facilitating in-depth analysis of these antibodies and paving the way for potential advancements in diagnostic and therapeutic approaches. As our understanding of oLAb continues to grow, their application in clinical practice and patient management remains a critical area of focus within cardiovascular research.

 

Related products

OxyStat Assay | BI-5007

Oxystat Oxidative Stress Test highlights:

• Determination of total oxidant capacity/status (TOC/TOS)
• Quick and easy assay to measure total peroxides in biological fluids

 

Literature

1. Antibodies against oxidized LDL-theory and clinical use. Steinerová A, Racek J, Stozický F, Zima T, Fialová L, Lapin A. Physiol Res. 2001;50(2):131-41. PMID: 11522041.
2. Transient reduction of autoantibodies against oxidized LDL in patients with acute myocardial infarction. Schumacher M, Eber B, Tatzber F, Kaufmann P, Halwachs G, Fruhwald FM, Zweiker R, Esterbauer H, Klein W. Free Radic Biol Med. 1995 Jun;18(6):1087-91. doi: 10.1016/0891-5849(94)00216-7. PMID: 7628731.
3. Overview of Clinical Relevance of Antibodies Against Oxidized Low-Density Lipoprotein (oLAb) Within Three Decades by ELISA Technology. Wonisch, W.; Tatzber, F.; Lindschinger, M.; Falk, A.; Resch, U.; Mörkl, S.; Zarkovic, N.; Cvirn, G. Antioxidants 2024, 13, 1560.
4. Antibodies against oxidized low density lipoproteins in pregnant women. Fialová L, Mikulíková L, Malbohan I, Benesová O, Stípek S, Zima T, Zwinger A. Physiol Res. 2002;51(4):355-61. PMID: 12449433.
5. Increased circulating oxidised low-density lipoprotein and antibodies to oxidised low-density lipoprotein in preeclampsia. Arifin R, Kyi WM, Che Yaakob CA, Yaacob NM. J Obstet Gynaecol. 2017 Jul;37(5):580-584. doi: 10.1080/01443615.2016.1269227. Epub 2017 Mar 30. PMID: 28358592.
6. Low-density lipoprotein oxidation biomarkers in human health and disease and effects of bioactive compounds. Winklhofer-Roob BM, Faustmann G, Roob JM. Free Radic Biol Med. 2017 Oct;111:38-86. doi: 10.1016/j.freeradbiomed.2017.04.345. Epub 2017 Apr 26. PMID: 28456641.

 

Our EZ4U (Easy for You) cell proliferation and cytotoxicity MTT assay was applied in a recent study exploring the role of pertuzumab, a monoclonal antibody that targets HER2, in disrupting the transactivation between the epidermal growth factor receptor (EGFR) and HER2 in HER2-positive cancers. The research focuses on understanding how this disruption could predict therapeutic outcomes based on the quantitative analysis of EGFR signaling input (1).

Measuring cell metabolic activity with EZ4U – MTT assay

 

EZ4U  Cell Viability & Cytotoxicity Assay (cat.no. BI-5000)

EASY FOR YOU (EZ4U)

• Non-radioactive & non-toxic
• Convenient single-step incubation  – for use on living cells
• Widely cited in more than 280 publications

 

1. Disrupting EGFR-HER2 Transactivation by Pertuzumab in HER2-Positive Cancer: Quantitative Analysis Reveals EGFR Signal Input as Potential Predictor of Therapeutic Outcome. Ujlaky-Nagy L, Szöllősi J, Vereb G. Int J Mol Sci. 2024 May 29;25(11):5978. doi: 10.3390/ijms25115978. PMID: 38892166.

 

Abstract

 

Related publications

Targeted therapeutic options and future perspectives for HER2-positive breast cancer. Wang J, Xu B. Signal Transduct Target Ther. 2019 Sep 13;4:34. doi: 10.1038/s41392-019-0069-2. PMID: 31637013.

 

 

for  ELISA and Luminex Assays and microRNA Analysis

With more than 30 years of expertise in the development and manufacturing of ELISA assay kits, Biomedica offers analytical testing services tailored for universities, clinical centers, as well as pharmaceutical and biotechnology industries. Our comprehensive range of analytical solutions ensures that we can provide exceptional service for your research or product development needs.

Biomarker Testing Service from Biomedica

Our highly trained staff will help you to achieve your specified goals and requirements. Biomedica has established a systematic process that guarantees results aligned with your exact specifications. Client satisfaction is our top priority. Having contributed to numerous successful research projects and publications, you will benefit from our expertise in analytical testing, paired with a customer-focused approach.

We offer:

• CUSTOMIZED Services – flexibility to meet your project needs
• EXPERTISE – trained and experienced laboratory staff
• QUALITY ASSURANCE – quality equipment adhering to strict quality guidelines
• TIMELINESS – rapid turn-around times to meet your deadlines
• RELIABILITY – verified and comprehensive results presented in an analytical report

 

Quality Assurance
We are committed to achieving the highest quality standards, recognizing that this is essential for both your success and ours. Our robust quality assurance system, quality control procedures, and testing methods clearly reflect this commitment. We hold ISO 9001:2015 quality management system and with 30 years of experience in the development and manufacturing of immunoassays, we offer expert knowledge and techniques that align with European quality standards.

Our Quality Assurance (QA) system is founded on comprehensive and well-structured standard operating procedures, ensuring that all analyses are traceable from the receipt of samples to the reporting of results. Regular inspections by regulatory bodies further affirm our strong compliance with current regulations.

• Routine internal audits and inspections
• Data assessed for traceability, integrity, and reliability
• Inspections to ensure adherence to protocols and laboratory SOPs

 

Find out more about our workflow for ELISA and Luminex and microRNA Services

Our analytical services include:  

ELISA (Enzyme Linked Immunabsorbent Assay) Kits

We offer services for our proprietary Biomedica assays (product catalogue) as well as ELISA Assay Kits from other suppliers, covering a wide range of biomarker analytes.

LUMINEX Technology Multiplex Assays

We utilize Luminex xMAP® (multiple analyte profiling) technology-based immunoassays to measure your samples, enabling the simultaneous detection and quantification of multiple biomarkers.

For additional details, please refer to our workflow chart or reach out to us directly to discuss how we can support your specific research project. 

NEXT-GENERATION SEQUENCING & RT-qPCR MICRO RNA SERVICES

We provide a comprehensive range of high-quality RNA services, including RNA extraction, next-generation sequencing (NGS), RT-qPCR, and custom analysis of microRNA signatures, all performed by our experienced laboratory staff. Our services include:

• RNA extraction from biofluids (serum, plasma, extracellular vesicles), cells, and tissues (quality control of total RNA utilizes Bioanalyzer chips).
• Next-generation sequencing (NGS).
• RT-qPCR
• Cell-type specific microRNA/mRNA analysis in complex tissues, along with custom analysis of microRNA signatures.

 

Share the details of your project with us!

For more details about our microRNA services, please visit our website or contact us directly (info.at.bmgrp.com).

 

Further reading

High-throughput proteomics: a methodological mini-review. Cui M, Cheng C, Zhang L. Lab Invest. 2022 Nov;102(11):1170-1181. doi: 10.1038/s41374-022-00830-7. Epub 2022 Aug 3. PMID: 35922478; PMCID: PMC9362039.

Circulating miRNAs in bone health and disease. Grillari J, Mäkitie RE, Kocijan R, Haschka J, Vázquez DC, Semmelrock E, Hackl M. Bone. 2021 Apr;145:115787. doi: 10.1016/j.bone.2020.115787. Epub 2020 Dec 8. PMID: 33301964.

C4d and graft loss in KTR with IgAN (abbrev. KTR: kidney transplant recipients, IgAN: IgA nephropathy)

C4d analysis has become an important diagnostic tool used in the evaluation of kidney transplant recipients (1). C4d is a fragment of the complement component C4 that is produced during the activation of the complement system. In the context of kidney transplantation, the presence of C4d in peritubular capillaries can indicate antibody-mediated injury and help assess the immune status of the transplanted kidney (2).

Our Anti-C4d Antibody (FITC)  has recently been used in a study evaluating whether recurrent IgA deposition, which is common after kidney transplantation, is associated with an increased risk of graft failure (1).

IgA nephropathy (IgAN) is the most prevalent type of kidney disorder. It can occur at any age but is more frequently diagnosed in young adults and adolescents (3). IgAN is marked by the deposition of immunoglobulin A (IgA) in the glomeruli, the filtering units of the kidney. The deposition of IgA, particularly in the mesangial cells of the glomeruli, leads to inflammation and kidney damage (4). The exact cause of IgAN is not fully understood, but it is believed to involve abnormal IgA production and a dysregulation of the immune system. IgA nephropathy (IgAN) has been shown to be associated with a risk for posttransplant recurrence (5, 6).

 C4d and graft loss in KTR with IgAN

The study involved sixty-seven kidney transplant recipients (KTR) of which 37% had recurrent IgA deposition (1). The results showed that “there were no clinical differences between KTR with and without recurrent IgA deposition. C4d was present in 48% of the biopsies. During a median follow-up of 9.6 [4.8-14] years, 18 (27%) KTR developed death-censored graft failure. Recurrent IgA deposition was not associated with graft failure. Of the evaluated complement factors, only C4d staining was associated with graft failure in KTR with recurrent IgA deposition” .  

The authors concluded that “ recurrent IgA deposition was not associated with graft failure in itself. C4d, when present, is strongly associated with graft loss in KTR with recurrent IgA deposition, suggesting a pathogenic role for the lectin pathway in recurrent IgAN.” (1).

Our C4d antibodies are used to identify the human complement split product C4d in paraffin and frozen sections as well as by flow cytometry.

 Anti-C4d Antibody | BI-RC4D

• widely cited in 100 publications
• for immunohistochemistry on paraffin embedded tissue and frozen sections
• use in kidney, heart, liver and other transplants

Anti-C4d Antibody (FITC) | BI-RC4D-FITC

• detection of cell- or solid-phase bound C4d and C4d split product by flow cytometry using FlowPRA® Class I and II screening test beads from One Lambda.

 

Literature

1. C4d, rather than C3d and C5b-9, is associated with graft loss in recurrent IgA deposition after kidney transplantation. Alkaff FF, Uffing A, Tiller G, Lammerts RGM, van den Heuvel MC, Bajema IM, Daha MR, van den Born J, Berger SP. Am J Nephrol. 2024 Aug 17. doi: 10.1159/000540986. Epub ahead of print. PMID: 39154645.
2. The diagnostic significance of C4d deposits, as an immunohistochemical proof of complement activation, in kidney glomerular pathologies and kidney transplantation. Hresko S, Madarova M, Dobosova M, Palusekova N, Niznerova P, Ziaran S, Varga I. Bratisl Lek Listy. 2024;125(5):275-280. doi: 10.4149/BLL_2024_41. PMID: 38624051.
3. Significance of C4d expression in peritubular capillaries concurrent with microvascular inflammation in for-cause biopsies of ABO-incompatible renal allografts. Cho H, Baek CH, Park SK, Kim H, Go H. Kidney Res Clin Pract. 2024 Jan;43(1):82-92. doi: 10.23876/j.krcp.22.221. Epub 2023 May 12. PMID: 37448281; PMCID: PMC10846988.
4. Complement Activation Is Associated With Crescents in IgA Nephropathy. Wang Z, Xie X, Li J, Zhang X, He J, Wang M, Lv J, Zhang H. Front Immunol. 2021 Sep 14;12:676919. doi: 10.3389/fimmu.2021.676919. PMID: 34594322; PMCID: PMC8477028.
5. Risk for graft loss in pediatric and young adult kidney transplant recipients due to recurrent IgA nephropathy. Engen RM, Bartosh SM, Smith JM, Perkins JD, Harshman LA.Am J Transplant. 2024 Jan;24(1):37-45. doi: 10.1016/j.ajt.2023.08.007. Epub 2023 Aug 16. PMID: 37595842.
6. Recurrence of IgA Nephropathy after Kidney Transplantation in Adults. Uffing A, Pérez-Saéz MJ, Jouve Tet al.,. Clin J Am Soc Nephrol. 2021 Aug;16(8):1247-1255. doi: 10.2215/CJN.00910121. PMID: 34362788; PMCID: PMC8455056.

Big ENDOTHELIN-1 a prognostic marker in CAD.  Endothelin-1 (ET-1) is the most potent vasoconstrictor peptide. This 21 amino acid peptide is the biologically active from that is rapidly cleared from the circulation. Its low concentrations and short half-life make it challenging to detect in serum and plasma samples. Big-Endothelin-1 (BigET-1) is the precursor peptide in the synthesis of Endothelin-1 (ET-1).  It circulates in higher concentrations  and also has a much longer half-life than ET-1. Therefore, measurement of plasma BigET-1 levels are an alternative approach for the indirect estimation of ET-1 release (1).

BigET-1 is primarily produced by endothelial cells and is produced through cleavage of “preproendothelin”, a larger precurser protein. The conversion of BigET-1 to the biologically active 21 amino acid ET-1, is a result the proteolytic cleavage by endothelin-converting enzymes (ECEs) (2). Big-ET-1 has been reported as an independent predictor of cardiovascular mortality in patients with chronic heart failure as determined in a large cohort study in more than 2800 individuals (3). In addition, Big ET-1 has been shown to be a strong and independent predictor of mortality in patients with moderate to severe light chain cardiac amyloidosis (AL-CA) , which may indicate a possible role for risk stratification in patients with this disease (4).

Big ENDOTHELIN-1 can easily be measured in serum and plasma samples.

Biomedica Big Endothelin ELISA Assay 

• EASY – can be used in every lab
• ROBUST & fully VALIDATED (following international quality guidelines)
• HIGHLY SENSTIVE – 0.02 pmol/l (= 0.086 pg/ml)
• GOOD ANALYTE STABILITY in serum and plasma

 

Download your protocol booklet  here

Big ENDOTHELIN-1 a prognostic marker in CAD

The Biomedica BigET-1 ELISA assay was highlighted in this large cohort study of nearly 8000 prediabetic and diabetic patients with stable Coronary Artery Disease (CAD): Prognostic Value of Plasma Endothelin-1 in Predicting Worse Outcomes in Patients with Prediabetes and Diabetes and Stable Coronary Artery Diseases. Yang C et al., Diabetes Metab J. 2024. 

Key findings

• Plasma BigET-1 level is an independent predictor of #cardiovascular events (CVEs) in patients with stable CAD. 

• BigET-1 remains independently associated with worse cardiovascular outcomes in prediabetic and diabetic patients but not in patients with normoglycemia.

• Patients with diabetes and high BigET-1 levels were associated with the highest risk of CVEs in patients with stable CAD.
• Targeting ET-1 pathways may help manage CAD in individuals with dysglycemia.

 

Literature

1. Biomarkers and Precision Medicine in Heart Failure . Nasrien E. Ibrahim et al., Heart Failure: a Companion to Braunwald’s Heart Disease (Fourth Edition), 2020.
2. Endothelin-1 levels and cardiovascular events. Jankowich M, Choudhary G. Trends Cardiovasc Med. 2020 Jan;30(1):1-8. doi: 10.1016/j.tcm.2019.01.007.PMID: 30765295.
3. Propeptide big-endothelin, N-terminal-pro brain natriuretic peptide and mortality. The Ludwigshafen risk and cardiovascular health (LURIC) study. Gergei I, Krämer BK, Scharnagl H, Stojakovic T, März W, Mondorf U. Biomarkers. 2017; 22(3-4):315-320. doi: 10.1080/1354750X.2016.1252969. PMID: 27788598.
4. Prognostic value of plasma big endothelin-1 in patients with light chain cardiac amyloidosis. Chen Z, Shi A, Wang Z, Chen Y, Lin Y, Su M, Dong H, Laptseva N, Hu Y, Flammer AJ, Duru F, Jin W, Chen L. Heart. 2024; 26;110(18):1124-1132. doi: 10.1136/heartjnl-2024-324000. PMID: 39084705.
5. Prognostic Value of Plasma Endothelin-1 in Predicting Worse Outcomes in Patients with Prediabetes and Diabetes and Stable Coronary Artery Diseases. Yang C, Zhu CG, Guo YL, Wu NQ, Dong Q, Xu RX, Wu YJ, Qian J, Li JJ. Diabetes Metab J. 2024 Sep;48(5):993-1002. doi: 10.4093/dmj.2023.0410. Epub 2024 Aug 21. PMID: 39165112.

 

Further reading

• Plasma concentration of big endothelin-1 and its relation with plasma NT-proBNP and ventricular function in heart failure patients. Rivera M, Cortés R, Portolés M, Valero R, et al., Rev Esp Cardiol. 2005 Mar;58(3):278-84. Spanish. PMID: 15766450.

• Endothelin: 30 Years From Discovery to Therapy. Barton M, Yanagisawa M. Hypertension. 2019; 74(6):1232-1265.

 

VANIN-1 a biomarker for survival in PAD – Peripheral artery disease (PAD) is a condition characterized by the narrowing of the peripheral arteries, often due to atherosclerosis, which reduces blood flow to the limbs, particularly the legs (1). This can lead to symptoms such as leg pain, cramping, and weakness during physical activity. In more severe cases, PAD can result in critical limb ischemia, ulcers, or even gangrene. It is closely associated with cardiovascular conditions and risk factors, including high blood pressure, diabetes, and chronic kidney disease.

Chronic kidney disease (CKD) significantly increases the risk of developing peripheral artery disease (PAD) and is also a common co-morbidity factor that is associated with PAD (2). Despite its clinical significance, there is currently no specific marker available for conducting a functional risk assessment of kidney disease patients suffering from peripheral artery disease (PAD), particularly in the early stages.

VANIN-1 a biomarker for survival in PAD 

In search of novel biomarkers that may serve as tools of risk assessment, Zierfuss B. and colleagues investigated the relationship between urinany Vanin-1 (uVNN-1) as a marker of kidney disease and PAD severity (3). The study included patients with stable PAD (n = 304) who were followed up for up to 10 years. Urinary Vanin-1 (uVNN1) was measured by an enzyme-linked immunosorbent assay (ELISA) from Biomedica. Urinary Vanin-1 (uVNN1) concentration were normalized to urine creatinine levels (uVNN1/Cr).

The results of the study demonstrate that uVNN-1 is an independent link to both all-cause and cardiovascular mortality in patients with peripheral artery disease (PAD). As a result, uVNN1/Cr may serve as a practical and accessible marker for risk stratification in early kidney disease patients with PAD, aiding in the identification of those patients who are at high risk for fatal events.

Human VANIN -1 (urine) ELISA Assay Kit  (cat. no. BI-VNN1)

• The assay is optimized for human urine samples
• Characterized antibodies enable high SPECIFICITY
• Rigorously validated assay following international quality guidelines
• Easy and quick one-step ELISA

 

 

Related products

-Mouse/rat Vanin-1 ELISA

-Nephrology and Transplant: FGF23, Endostatin, Anti C4d

-Cardiovascular: NT-proBNP, Endothelins, proANP, NT-proCNP

 

About Vanin-1 (VNN1)

Vascular non-inflammatory molecule-1 or VANIN-1 (VNN1) is a protein that is part of the Vanin family of enzymes that possesses pantetheinase activity and primarily carries out its physiological functions through the products of its enzyme catalysis, such as pantothenic acid and cysteamine. VNN1 is involved in various biological processes, including inflammation, oxidative stress, and tissue repair (4). Vanin-1 is primarily expressed in certain tissues, such as the liver, kidneys, and immune cells. The capacity of  VNN1 to influence various metabolic pathways and its role in oxidative stress in either worsening or alleviating pathological processes, has led to the hypothesis that it is a crucial factor in disease progression (5).

The potential of Vanin-1 as a marker of acute kidney injury and as a predictor of acute pyelonephritis in young children with urinary tract infection has been investigated, particularly as urinary VNN1 concentrations are higher in these patients (6, 7).

Literature

1. Peripheral Artery Disease: A Comprehensive Updated Review. Shamaki GR, Markson F, Soji-Ayoade D, Agwuegbo CC, Bamgbose MO, Tamunoinemi BM. Curr Probl Cardiol. 2022; 47(11):101082. doi: 10.1016/j.cpcardiol.2021.101082. PMID: 34906615.
2. The Impact of Chronic Kidney Disease on Peripheral Artery Disease and Peripheral Revascularization. Serra R, Bracale UM, Ielapi N, Del Guercio L, Di Taranto MD, Sodo M, Michael A, Faga T, Bevacqua E, Jiritano F, Serraino GF, Mastroroberto P, Provenzano M, Andreucci M.Int J Gen Med. 2021; 14:3749-3759. doi: 10.2147/IJGM.S322417. PMID: 34326661.
3. Urinary vanin-1 as a novel biomarker for survival in peripheral artery disease. Zierfuss B, Karlinger A, Bojic M, Koppensteiner R, Schernthaner GH, Höbaus C. Vasc Med. 2024; 29(4):390-397. doi: 10.1177/1358863X241240428. PMID: 38607943.
4. Vanin 1: Its Physiological Function and Role in Diseases. Bartucci R, Salvati A, Olinga P, Boersma YL. Int J Mol Sci. 2019; 20(16):3891. doi: 10.3390/ijms20163891. PMID: 31404995.
5. Vanin1 (VNN1) in chronic diseases: Future directions for targeted therapy. Yu H, Cui Y, Guo F, Zhu Y, Zhang X, Shang D, Dong D, Xiang H. Eur J Pharmacol. 2024; 962:176220. doi: 10.1016/j.ejphar.2023.176220. PMID: 38042463.
6. Urinary vanin-1 for predicting acute pyelonephritis in young children with urinary tract infection: a pilot study. Krzemień G, Pańczyk-Tomaszewska M, Górska E, Szmigielska A Biomarkers. 2021; 26(4):318-324. doi: 10.1080/1354750X.2021.1893813. PMID: 33656956
7. A Novel Biomarker for Acute Kidney Injury, Vanin-1, for Obstructive Nephropathy: A Prospective Cohort Pilot Study. Washino S, Hosohata K, Oshima M, Okochi T, Konishi T, Nakamura Y, Saito K, Miyagawa T. Int J Mol Sci. 2019; 20(4):899. doi: 10.3390/ijms20040899. PMID: 30791405.

November is Diabetes Awareness Month bringing attention to diabetes and its impact on millions of individuals.

Diabetes mellitus has emerged as the third most significant non-communicable disease, following cardiovascular diseases and cancer. This condition encompasses a group of metabolic disorders marked by chronic hyperglycemia resulting from various causes, along with inadequate insulin secretion and impaired insulin action. According to the most recent statistics from the International Diabetes Federation, the global number of individuals with diabetes reached 530 million in 2021, with projections suggesting it could exceed 780 million by 2045. Due to the long-term nature of the disease, diabetes can lead to damage across multiple body systems or organs, resulting in various complications (1, 2). Beyond the more commonly known complications of diabetes such as heart disease, diabetes can also affect the skeletal system. This severe complication of diabetes leads to bone loss potentially resulting in osteoporosis and increased fracture risk.

Identifying biomarkers that may predict fracture risk in individuals with diabetes is crucial for improving patient care.

Sclerostin and Fracture Risk Prediction in Diabetes

Sclerostin (SOST) is a bone-related protein that is mainly produced by osteocytes, bone cells embedded in the bone matrix. Sclerostin is considered to be one of the major regulators of bone formation. It is a soluble antagonist of the Wnt signaling pathway and its inactivation leads to bone degradation, while the  of Wnt signaling promotes bone formation (3). Sclerostin has been a target of therapeutic antibodies for osteoporosis treatment due to its role in inhibiting bone formation.

Bone as an endocrine organ

Research indicates that bone, which is involved in lipid and glucose metabolism, is increasingly recognized as an endocrine organ. Recent findings suggest that sclerostin contributes to disorders related to lipid and glucose metabolism (4). Studies have shown that Sclerostin levels are increased in individuals with prediabetes and correlated with insulin resistance in the skeletal muscle, liver, and adipose tissue (5). In addition, Sclerostin levels have been shown to be negatively associated with insulin sensitivity in obese but not in lead woman (6).

Further studies have revealed that increased serum Sclerostin levels are associated with vertebral fractures in patients with type 2 diabetes mellitus (7, 8). Sclerostin, has also been suggested to have predictive value for fracture risk in patients with diabetes (9).

Sclerostin – a promising circulating marker of diabetic bone disease

Sclerostin has emerged as a promising circulating marker of diabetic bone disease. It may not only reflect the degree of osteocyte dysfunction and the suppression of bone formation that occurs in this disease, but it may also potentially reflect the vascular alterations that are associated with specific bone alterations such as cortical porosity (10).

Additional research is essential to enhance the understanding of biochemical markers in the assessment of diabetic bone disease. Specifically, the ability of bone markers to forecast fracture risk needs further examination.

Circulating Sclerostin levels can reliably be measured in human serum and plasma samples with a conventional SCLEROSTIN ELISA Assay Kit.

Sclerostin ELISA (cat. no. BI-20492)

• MOST referenced in more than 300 citations
• LOW sample volume – 20µl sample /well
• For SERUM & PLASMA samples
• RELIABLE – full validation package

 

Bioactive Sclerostin ELISA (cat. no. BI-20472)

• CHARACTERIZED ANTIBODIES – targeting the receptor binding region
• RIGOROUSLY validated for clinical samples
• LOW sample volume – 20µl sample /well
• RELIABLE – full validation package

 

Literature

1. International Diabetes Federation – Facts and Figures
2. Diabetes mellitus, the fastest growing global public health concern: Early detection should be focused. Hossain MJ, Al-Mamun M, Islam MR. Health Sci Rep. 2024; 7(3):e2004. doi: 10.1002/hsr2.2004. PMID: 38524769.
3. Role of Wnt signaling and sclerostin in bone and as therapeutic targets in skeletal disorders. Marini F, Giusti F, Palmini G, Brandi ML. Osteoporos Int. 2023; 34(2):213-238. doi: 10.1007/s00198-022-06523-7. PMID: 35982318.
4. The role of sclerostin in lipid and glucose metabolism disorders. Jiang H, Li D, Han Y, Li N, Tao X, et al., Biochem Pharmacol. 2023; 215:115694. doi: 10.1016/j.bcp.2023.115694. PMID: 37481136.
5. Sclerostin and Insulin Resistance in Prediabetes: Evidence of a Cross Talk Between Bone and Glucose Metabolism. Daniele G, Winnier D, Mari A, Bruder J, Fourcaudot M, Pengou Z, Tripathy D, Jenkinson C, Folli F. Diabetes Care. 2015; 38(8):1509-17. doi: 10.2337/dc14-2989. PMID: 26084344.
6. Serum sclerostin is negatively associated with insulin sensitivity in obese but not lean women. Aznou A, Meijer R, van Raalte D, den Heijer M, Heijboer A, de Jongh R. Endocr Connect. 2021; 10(2):131-138. doi: 10.1530/EC-20-0535. PMID: 33480863.
7. Increased serum sclerostin and decreased serum IGF-1 are associated with vertebral fractures among postmenopausal women with type-2 diabetes. M.S. Ardawi, D.H. Akhbar, A. Alshaikh, M.M. Ahmed, M.H. Qari, A.A. Rouzi, et al. Bone, 56 (2013), pp. 355-362
8. Elevated sclerostin levels are associated with vertebral fractures in patients with type 2 diabetes mellitus. Yamamoto M, Yamauchi M, Sugimoto T. J Clin Endocrinol Metab. 2013; 98(10):4030-7. doi: 10.1210/jc.2013-2143. PMID: 23894157.
9. Fracture risk assessment in diabetes mellitus. Front Endocrinol (Lausanne). Chen W, Mao M, Fang J, Xie Y, Rui Y. 2022; 13:961761. doi: 10.3389/fendo.2022.961761. PMID: 36120431.
10. Biochemical Markers of Bone Fragility in Patients with Diabetes. A Narrative Review by the IOF and the ECTS. Meier C, Eastell R, Pierroz DD, Lane NE, Al-Daghri N, Suzuki A, Napoli N, Mithal A, Chakhtoura M, El-Hajj Fuleihan G, Ferrari S. J Clin Endocrinol Metab. 2023; 108(10):e923–36. doi: 10.1210/clinem/dgad255. PMID: 37155585.

 

 

Detectable values in serum and plasma samples

We´re thrilled to offer our customers a SIGNIFICANT PRICE DROP of minus 15% !!!

on our human Interleukin-6 ELISA assay kit.

Quality, fully validated kit, ready to use reagents for affordable and efficient research!

Biomedica´s human Interleukin-6 (IL-6) ELISA is highly sensitive with measurable values in serum and in plasma samples.

Features include:

• Standardized– use of WHO intern. standards for kit calibration & harmonization 
• High Specificity – using characterized epitope-mapped antibodies
• User-Friendly – ready to use color coded, prediluted standards & controls

 

Human IL-6 ELISA Assay Kit (cat. no. BI-IL6)

Contact us or your local representative click here

Just use Promotion Code: BCIL62024 on your order.

Human IL-6 ELISA Assay Kit (cat. no. BI-IL6)

• Format: 12×8 wells
• Detection limit/Sensitivity: 0.28 pg/ml
• Assay – Dynamic Range: 0 – 200 pg/ml
• Incubation Time: 4 hours 30 minutes
• Sample Type: Serum, Plasma, Cell Culture Supernatants, Urine
• Sample Volume: 100 µl
• Alternative Name: Interleukin 6

 

Links to IL-6 ELISA : Protocol Booklet,  Validation Data File, Material Safety Data Sheet MSDS

The Human IL-6 High Sensitivity ELISA Assay is Developed and Manufactured in Austria by Biomedica

 Assay Principle

The Human IL-6 High Sensitivity ELISA Assay Kit is a sandwich enzyme immunoassay that has been optimized and fully validated for the quantitative determination of human IL-6 in serum, EDTA-plasma, citrate plasma, and heparin plasma. Validation experiments have been performed according to international quality guidelines (ICH/ FDA/ EMEA). Cell culture supernatant and urine samples are compatible with this ELISA. The IL-6 ELISA assay recognizes both natural and recombinant human IL-6. The assay employs highly purified epitope mapped antibodies as well as human serum-based standards and controls. The figure below explains the principle of the human IL-6 sandwich ELISA:

First, STD/sample/CTRL are pipetted into wells. The wells are precoated with a recombinant anti-human IL-6 antibody. The soluble IL-6 that is present in the sample binds to the pre-coated anti-IL-6 antibody in the well. After an incubation step, the microtiter plate is washed where all non-specific unbound material is removed. In the next step, the biotinylated anti-IL-6 antibody is pipetted into the wells. This antibody reacts with the IL-6 present in the sample and forms a so-called sandwich. During the next washing step all unbound antibody is removed. After washing, the conjugate (streptavidin-HRPO) is added to the wells that reacts with the biotinylated anti-IL-6 antibody. After a further washing step, the substrate (tetramethylbenzidine; TMB) is pipetted into the wells. The enzyme catalyzed color change of the substrate is directly proportional to the amount of IL-6 present in the sample which is detectable with a standard microtiter plate ELISA reader. Thereafter, a dose response curve of the absorbance (optical density, OD at 450 nm) versus standard concentration is generated, using the values obtained from the standards. The concentration of soluble IL-6 in the sample is determined directly from the dose response curve.

Learn more about our validation process and our quality guidelines

Related ELISA kits

Human VEGF, human Angiopoietin-2, mouse/rat Angiopoietin-2

 

About Interleukin-6 (IL- 6)

Il-6 is a cytokine which acts as a type of signaling molecule that plays a critical role in the immune response, inflammation, and metabolism. It is produced by various types of cells, including macrophages, T cells, and fibroblasts, and acts on multiple cell types to modulate immune functions and systemic responses.

Key Functions of IL-6

1. Role in Inflammation: IL-6 is involved in the acute phase response to inflammation and infection. It stimulates the production of acute-phase proteins by the liver, such as C-reactive protein (CRP).
2. Immune Regulation: This cytokine influences the differentiation of T cells and B cells, enhancing the body’s ability to respond to pathogens. It also promotes the growth and differentiation of specific immune cells.
3. Metabolism: IL-6 plays a role in metabolic processes, including glucose metabolism and lipid metabolism. Dysregulation of IL-6 signaling is linked to metabolic disorders such as obesity and type 2 diabetes.
4. Bone Metabolism: IL-6 is involved in bone remodeling. It can stimulate the formation of osteoclasts, the cells responsible for bone resorption, potentially contributing to conditions such as osteoporosis.
5. Chronic Conditions: Elevated levels of IL-6 are associated with chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and certain malignancies. It is also implicated in the cytokine storm seen in severe cases of COVID-19.

 

Clinical Relevance

Due to its central role in inflammation and immune response, IL-6 has become a target for therapeutic interventions in various conditions. Several IL-6 inhibitors, such as tocilizumab, are used in the treatment of autoimmune diseases and other inflammatory conditions. Monitoring IL-6 levels can also provide insights into disease progression and response to treatment in conditions characterized by inflammation.

Conclusion:

IL-6 is a multifaceted cytokine with critical roles in immune responses, inflammation, and metabolism. Its dysregulation can contribute to various diseases, making it an important focus in both research and clinical settings. Understanding its mechanisms and effects can help in developing targeted therapies for inflammatory and metabolic disorders.

Literature

• Interleukin 6: at the interface of human health and disease. Grebenciucova E, VanHaerents S. Front Immunol. 2023 Sep 28;14:1255533. doi: 10.3389/fimmu.2023.1255533. PMID: 37841263; PMCID: PMC10569068.
• Interleukin-6 signalling in health and disease. Rose-John S. F1000Res. 2020 Aug 20;9:F1000 Faculty Rev-1013. doi: 10.12688/f1000research.26058.1. PMID: 32864098; PMCID: PMC7443778.
• Recent advances in the role of interleukin-6 in health and disease. Peppler WT, Townsend LK, Wright DC. Curr Opin Pharmacol. 2020 Jun;52:47-51. doi: 10.1016/j.coph.2020.04.010. Epub 2020 Jun 18. PMID: 32563931.

Sepsis is a life-threatening medical condition that arises when the body’s response to an infection triggers widespread inflammation, leading to tissue damage and organ dysfunction. Early recognition and prompt treatment are crucial as sepsis can result in multi-organ failure and death (1). Timely administration of antibiotics and supportive care significantly improve outcomes, highlighting the importance of awareness and rapid intervention in managing this critical condition.

For sepsis, a range of biomarkers exist but have not been completely effective identifying patients at the onset of sepsis or in predicting their prognosis and the anticipated severity of organ failure. Furthermore, the mechanisms underlying the uncontrolled infection, dysregulated immune response, and subsequent organ failure remain unclear, highlighting the need for further research.

A recent study by Hohlstein P and colleagues (2) explores the role of soluble Neuropilin-1 (sNRP-1) in critical illness and sepsis and evaluates its potential as a biomarker in this context.

Key findings of the study:

• Critically ill and septic patients exhibit higher levels of circulating sNRP-1.
• sNRP-1 levels correlate with organ failure, particularly hepatic and kidney function impairment.
• Long-term survivors have lower levels of sNRP-1 upon admission to the ICU.

soluble NEUROPILIN-1 in sepsis correlates with organ dysfunction

Soluble Neuropilin-1 (sNRP-1) was measured in human serum samples with the

Biomedica soluble Neuropilin-1 ELISA assay (cat. no. BI-20409)

Assay Highlights:

• Only assay that detects free and ligand-bound soluble Neuropilin-1
• Highly specific and epitope mapped antibodies 
• Extensively validated according to FDA/ICH/EMEA guidelines

 

Links to the  Protocol Booklet and Validation Data

 

Soluble Neuropilin-1 Is Elevated in Sepsis and Correlates with Organ Dysfunction and Long-Term Mortality in Critical Illness. 

Abstract

Critical illness and sepsis may cause organ failure and are recognized as mortality drivers in hospitalized patients. Neuropilin-1 (NRP-1) is a multifaceted transmembrane protein involved in the primary immune response and is expressed in immune cells such as T and dendritic cells. The soluble form of NRP-1 (sNRP-1) acts as an antagonist to NRP-1 by scavenging its ligands. The aim of this study was to determine the value of sNRP-1 as a biomarker in critical illness and sepsis. We enrolled 180 critically ill patients admitted to a medical intensive care unit and measured serum sNRP-1 concentrations at admission, comparing them to 48 healthy individuals. Critically ill and septic patients showed higher levels of sNRP-1 compared to healthy controls (median of 2.47 vs. 1.70 nmol/L, p < 0.001). Moreover, sNRP-1 was also elevated in patients with sepsis compared to other critical illness (2.60 vs. 2.13 nmol/L, p = 0.01), irrespective of disease severity or organ failure. In critically ill patients, sNRP-1 is positively correlated with markers of kidney and hepatic dysfunction. Most notably, critically ill patients not surviving in the long term (one year after admission) showed higher concentrations of sNRP-1 at the time of ICU admission (p = 0.036), with this association being dependent on the presence of organ failure. Critically ill and septic patients exhibit higher serum concentrations of circulating sNRP-1, which correlates to organ failure, particularly hepatic and kidney dysfunction.

Keywords: Neuropilin-1; critical illness; human; immune system; inflammation; intensive care unit; mortality; prognosis; sepsis; survival

Literature

1. Sepsis and septic shock. Cecconi M, Evans L, Levy M, Rhodes A. Lancet. 2018 Jul 7;392(10141):75-87. doi: 10.1016/S0140-6736(18)30696-2. Epub 2018 Jun 21. PMID: 29937192.
2. Soluble Neuropilin-1 Is Elevated in Sepsis and Correlates with Organ Dysfunction and Long-Term Mortality in Critical Illness. Hohlstein P, Schumacher E, Abu Jhaisha S, Adams JK, Pollmanns MR, Schneider CV, Hamesch K, Horvathova K, Wirtz TH, Tacke F, Trautwein C, Weiskirchen R, Koch A. Int J Mol Sci. 2024 May 16;25(10):5438. doi: 10.3390/ijms25105438. PMID: 38791476.

 

Kidney dysfunction causes disruptions in bone and mineral metabolism and changes in the regulators of the renal-bone axis through various mechanisms. Studies have demonstrated that fibroblast growth factor 23 (FGF23) and inflammatory markers rise, while iron status may decline (1, 2). In healthy individuals, FGF23 is regulated by phosphate, Vitamin D (1,25(OH)₂D), and parathyroid hormone (PTH). However in the early stages of chronic kidney disease (CKD), FGF23 levels begin to increase even before plasma phosphate levels increase (3).

Thus, CKD causes disruptions in bone and mineral metabolism that also includes the regulatory hormones, resulting chronic kidney disease-mineral bone disorder (CKD-MBD).

Bone biomarkers in early renal impairment

A recent study investigated the effects of Vitamin D supplementation in a cohort of healthy community-dwelling older people. Baseline blood concentrations of bone regulatory markers including Sclerostin (SOST), Dickkopf-related Protein 1 (DKK1); Osteoprotegerin (OPG) and soluble RANKL (sRANKL), Fibroblast growth factor 23 (intact and c-terminal FGF23) and TNF-alpha, Interleukin-6 (IL-6) were analysed. The results showed that SOST, cFGF23, iFGF23, PTH and TNF-alpha were elevated in the group of individuals with early kidney impairment compared to those with normal kidney function. Following Vitamin D supplementation, only cFGF23, 25(OH)D, and IL-6 showed differences between the groups.

The study identified alterations in the renal bone-axis that occur prior to clinical monitoring of patients. Early diagnosis in the initial stages of renal impairment may offer opportunities for preventing the progression of renal disease and chronic kidney disease-mineral bone disorder (CKD-MBD).

Learn more: Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation. Christodoulou M et al., Age Ageing. 2024; 53(5):afae096. doi: 10.1093/ageing/afae096. PMID: 38770543.

Bone biomarkers in early renal impairment

Biomedica offers quality ELISA Assay Kits for bone regulatory biomarkers

Sclerostin (SOST; cat.no. BI-20492)

Bioactive Sclerostin (bioSOST; cat. no. BI-20472)

OPG  (Osteoprotegerin; cat.no. BI-20403)

RANKL (soluble RANKL; cat.no. BI-20462)

DKK-1  (Dickkopf-1; cat.no. BI-20413)

FGF23 intact  (Fibroblast growth factor-23 intact; cat.no. BI-20700)

FGF23 C-terminal  (Fibroblast growth factor-23 C-terminal; cat.no. cat.no. BI-20702)

 

Key Features

• TRUSTED – cited in over 1000 publications
• Kit validations follows international quality guidelines
• Ready to use standards and controls included
• Developed & manufactured by Biomedica in Austria

 

Literature

1. Iron Deficiency Anemia in Chronic Kidney Disease. Gafter-Gvili A, Schechter A, Rozen-Zvi B. Acta Haematol. 2019;142(1):44-50. doi: 10.1159/000496492. Epub 2019 Apr 10. PMID: 30970355.
2. Iron-Deficiency Anemia in CKD: A Narrative Review for the Kidney Care Team. Hain D, Bednarski D, Cahill M, Dix A, Foote B, Haras MS, Pace R, Gutiérrez OM. Kidney Med. 2023 May 25;5(8):100677. doi: 10.1016/j.xkme.2023.100677. PMID: 37415621; PMCID: PMC10319843.
3. The bone-renal axis in early chronic kidney disease: an emerging paradigm. Danziger J. Nephrol Dial Transplant. 2008 Sep;23(9):2733-7. doi: 10.1093/ndt/gfn260. Epub 2008 May 9. PMID: 18469306.

 

Breast cancer is the most prevalent cancer among women globally. Enhancing our knowledge of how breast cancer develops, progresses, and metastasizes could aid in decreasing the risk and impact of the disease. Circulating proteins in serum or plasma can serve as biomarkers of cancer progression and prognosis while also serving as potential therapeutic targets. Enhancing our understanding on how cancers originate, grow and spread could aid in lowering the risk and impact of the disease. Recent research on cancer markers has highlighted novel protein biomarkers and promising therapeutic targets in breast cancer:

PERIOSTIN, NEUROPILIN-1, SEMAPHORIN 4D, and LEUCINE-RICH ALPHA-2-GLYCOPROTEIN. These proteins can be easily detected in human serum and plasma using ELISA assays.

Novel Biomarkers in Breast Cancer

PERIOSTIN (alternative names: POSTN, OSF-2, OSF2, PDLPN, PN)

Periostin is a matricellular protein that plays a significant role in various physiological and pathological processes, including tissue remodeling, inflammation, and wound healing. In the context of breast cancer, periostin has garnered attention due to its involvement in tumorigenesis, progression, and the tumor microenvironment.

Role of Periostin in Breast Cancer

Tumor Microenvironment: Periostin is often overexpressed in the extracellular matrix (ECM) of breast tumors (1). It interacts with various cells in the tumor microenvironment, including cancer-associated fibroblasts, immune cells, and endothelial cells, promoting tumor growth and metastasis. A recent study has demonstrated that Periostin drives extracellular matrix degradation, stemness, and chemoresistance in triple-negative breast cancer cells by activating specific signaling pathways (2).

Cell Signaling: Periostin can activate multiple signaling pathways that contribute to cancer progression. It is known to bind to integrins on the surface of cancer cells, which can lead to enhanced cell survival, proliferation, and migration. This signaling also supports processes such as epithelial-to-mesenchymal transition (EMT), a critical step in cancer metastasis.

Metastasis: Elevated levels of periostin have been associated with increased metastasis in breast cancer. Studies have indicated that higher periostin expression correlates with the aggressive behavior of breast cancer cells, particularly in triple-negative breast cancer (TNBC), which is known for its poor prognosis (3).

Periostin as a Potential Biomarker: Due to its association with poor outcomes and aggressive disease, periostin has been investigated as a potential biomarker for breast cancer. Its expression levels in tumor tissues or serum may provide insights into disease progression and treatment responses. Epithelial periostin expression is correlated with poor survival in patients with invasive breast carcinoma (3). High serum levels of Periostin have been demonstrated to be associated with poor survival in breast cancer (4).

Therapeutic Target: Given its role in promoting cancer progression, periostin presents a potential therapeutic target. Inhibition of periostin signaling may offer a novel strategy for treating aggressive breast cancer subtypes by disrupting the supportive tumor microenvironment (5).

Conclusion: Periostin plays a multifaceted role in breast cancer, affecting tumor growth, metastasis, and the tumor microenvironment. Its involvement in key molecular pathways and its potential utility as a biomarker make it a significant focus of ongoing research. Targeting periostin could open new avenues for therapy, particularly in aggressive forms of breast cancer, ultimately aiming to improve patient outcomes. Further studies are needed to fully elucidate its mechanisms and to evaluate its efficacy as a therapeutic target in clinical settings.

Periostin can reliably be measured in human blood samples with a conventional ELISA assay developed and manufactured by BIOMEDICA.

PERIOSTIN ELISA (cat. no. BI-20433)

• EASY – ready to use calibrators & controls included
• RELIABLE – validated according to international quality guidelines
• LOW sample volume- 10 µl / sample
• TRUSTED – widely cited

 

An in-depth characterization of the Biomedica Periostin ELISA has been published here: Characterization of a sandwich ELISA for the quantification of all human periostin isoforms. Gadermaier E et al., J Clin Lab Anal. 2018; 32(2):e22252.

 

Novel Biomarkers in Breast Cancer

NEUROPILIN-1 (alternative names: NRP1, BDCA4, CD304, NP1, NRP, VEGF165R)

Neuropilin-1 (NRP1) is a transmembrane protein that has emerged as an important player in breast cancer biology. It is involved in various cellular processes, including cell signaling, survival, and migration, and has been implicated in cancer progression and metastasis (6).

Role of Neuropilin-1 in Breast Cancer

Tumor Growth and Survival: Neuropilin-1 (NRP1) is expressed in both cancer cells and the surrounding stromal cells within the tumor microenvironment. It has been linked to enhanced cell survival and proliferation, contributing to tumor growth. Elevated NRP1 expression has been associated with aggressive breast cancer subtypes, such as triple-negative breast cancer (TNBC) (6). A recent study has demonstrated that high NRP1 expression is associated with shorter relapse- and metastasis-free survival specifically in ER-negative BrCa cohorts (7).

Angiogenesis: NRP1 plays a critical role in angiogenesis, the formation of new blood vessels from existing ones, which is crucial for tumor growth and metastasis. By interacting with vascular endothelial growth factor (VEGF) and its receptors, NRP1 promotes endothelial cell proliferation and migration, facilitating the tumor’s ability to establish a blood supply (8).

Metastasis: Neuropilin-1 expression has been shown to be associated with lymph node metastasis in breast cancer tissues (9). Increased levels of NRP1 in breast cancer have been correlated with a higher propensity for metastasis. Studies have shown that NRP1 facilitates the migration of cancer cells to distant sites, contributing to the spread of the disease and poorer patient outcomes.

Potential Biomarker: In breast cancer patients, soluble Neuropilin-1 has shown to be an independent marker of poor prognosis in early breast cancer (10). In addition NRP-1 has also been shown to be a potential biomarker of prognosis and invasive-related parameters in other cancers such as liver and colorectal cancer (11).

Therapeutic Target: Given its involvement in tumor growth, angiogenesis, and metastasis, NRP1 is being explored as a therapeutic target. Strategies to inhibit NRP1 function or block its signaling pathways could offer new avenues for breast cancer treatment, particularly for patients with aggressive or metastatic disease (12).

Conclusion: Neuropilin-1 is a significant factor in the biology of breast cancer, influencing tumor growth, metastasis, and interactions within the tumor microenvironment. Its role in promoting angiogenesis and facilitating aggressive cellular behaviors makes it an important target for ongoing research. Targeting NRP1 could provide new therapeutic approaches for breast cancer, potentially improving outcomes for patients, especially those with more aggressive forms of the disease. Further studies are needed to clarify its mechanisms and evaluate targeted therapies in clinical settings.

Neuropilin-1 (NRP1) can reliably be measured in human blood samples with a conventional ELISA assay developed and manufactured by BIOMEDICA.

Total soluble NEUROPILIN-1 ELISA (cat. no. BI-20409)

• EASY – ready to use calibrators & controls included
• RELIABLE – validated according to international quality guidelines
• LOW sample volume- 10 µl / sample
• TRUSTED – for citations click here

 

The Biomedica human NRP-1 ELISA is described in this following publication: Characterization of a sandwich ELISA for quantification of total human soluble neuropilin-1. Gadermaier E, Tesarz M, Wallwitz J, Berg G, Himmler G. J Clin Lab Anal. 2019; 33(7):e22944. doi: 10.1002/jcla.22944. PMID: 31219204.

 

Novel Biomarkers in Breast Cancer

SEMAPHORIN 4D (alternative names: Sema4D, C9orf164, SEMAJ, CD100, BB18, GR3, CD100, COLL4)

Semaphorin 4D (Sema4D) is a member of the semaphorin family of proteins, which are known for their roles in cell signaling, axon guidance, and immune regulation (13). In the context of breast cancer, Sema4D has garnered attention for its involvement in tumor growth, metastasis, and the tumor microenvironment.

About Semaphorin 4D in Breast Cancer

Tumor Growth and Progression: Sema4D can influence the behavior of cancer cells, promoting survival and proliferation. It may also aid in the establishment of a supportive tumor microenvironment. In a study researchers have shown that Sema4D was expressed at higher levels in breast cancer cell lines compared with the normal human breast epithelial cell lines (14).

Angiogenesis: Sema4D is involved in the formation of new blood vessels (angiogenesis), which is vital for tumor growth. It can modulate the activity of endothelial cells, thereby supporting the vascularization of tumors (14).

Immune Evasion: Sema4D can affect the immune response to tumors. It may contribute to the suppression of T-cell responses, allowing cancer cells to evade immune detection and destruction.

Metastasis: The expression of Sema4D has been linked to increased metastatic potential in breast cancer. It may facilitate the migration and invasion of cancer cells to distant sites in the body. In a recent study researchers have found that Semaphorin 4D promotes skeletal metastasis in breast cancer (15).

A decreased expression of semaphorin 4D and plexin-B in breast cancer has been shown to be associated with recurrence and poor prognosis in a breast cancer cohort (16).

Biomarker Potential: Research suggests that Sema4D levels could serve as a potential biomarker for breast cancer progression and prognosis, although further studies would be needed to establish its clinical utility.

The potential link between Sema4D and estrogen receptor signaling was proposed in a study measuring circulating Sema4D plasma levels at primary diagnosis and in a follow-up sample 12 months after surgery in a cohort of 46 pre- and postmenopausal women with primary estrogen receptor positive breast cancer receiving adjuvant tamoxifen. The finding potentially represents an additional mechanism of the bone-protective properties of tamoxifen (17).

Therapeutic Targeting:  Due to its involvement in various aspects of cancer biology, Sema4D is being explored as a potential therapeutic target. Inhibiting its function might help in reducing tumor growth and improving the effectiveness of existing treatments. A study demonstrated that a Sema4D antibody in combination with either CTLA-4 or PD-1 blockade enhanced rejection of tumors or tumor growth delay, resulting in prolonged survival with either treatment (18).

Conclusion: Sema4D plays a multifaceted role in breast cancer pathology, influencing tumor growth, metastasis, and immune interactions. Ongoing research is essential to fully understand its mechanisms and to explore its potential as a target for therapeutic intervention.

Soluble SEMAPHORIN 4D ELISA (cat. no. BI-20405)

• EASY – ready to use calibrators & controls included
• RELIABLE – first validated according to international quality guidelines
• LOW sample volume- 10 µl / sample – no predilution!
• Reference values for healthy individuals provided

 

An in-depth characterization of the Biomedica Semaphorin 4D ELISA has been published here: A high-sensitivity enzyme immunoassay for the quantification of soluble human semaphorin 4D in plasma. Laber, A., Gadermaier, E., Wallwitz, J., Berg, G., Himmler, G., 2019. Anal. Biochem. 574, 15–22.  PMID: 30879960

 

Novel Biomarkers in Breast Cancer

LEUCINE-RICH ALPHA-2-GLYCOPROTEIN (alternative names: LRG, LRG1, HMFT1766) 

Leucine-rich alpha-2-glycoprotein (LRG) is a protein that has been studied in various diseases, including cancer. It is known for its involvement in inflammation and immune responses. In the context of breast cancer, LRG has attracted interest for its potential role as a biomarker and its involvement in the tumor microenvironment. For more information on LRG-1 as a prognostic marker for breast cancer survival please click here

LRG ELISA Assay Highlights (cat. no. BI-LRG)

• CONVENIENT – ready to use reagents and controls included
• RELIABLE – rigorously validated following international quality guidelines
• EASY – results available in 3 hours

 

Related products

DKK-1 (Dickkopf-1) ELISA kit (cat. no. BI-20413) 

• Direct measurement – no sample pre-dilution
• Day test – all reagents included
• Widely cited +180 references!

 

Literature 

1.  Expression of periostin in breast cancer cells. Ratajczak-Wielgomas K, Grzegrzolka J, Piotrowska A, Matkowski R, Wojnar A, Rys J, Ugorski M, Dziegiel P. Int J Oncol. 2017; 51(4):1300-1310. doi: 10.3892/ijo.2017.4109.
2. Periostin drives extracellular matrix degradation, stemness, and chemoresistance by activating the MAPK/ERK signaling pathway in triple-negative breast cancer cells. Wu J, Li J, Xu H, Qiu N, Huang X, Li H. Lipids Health Dis. 2023; 16;22(1):153. doi: 10.1186/s12944-023-01912-1.
3. Epithelial periostin expression is correlated with poor survival in patients with invasive breast carcinoma. Kim GE, Lee JS, Park MH, Yoon JH. PLoS One. 2017; 21;12(11):e0187635. doi: 10.1371/journal.pone.0187635. PMID: 29161296..
4. High serum levels of periostin are associated with a poor survival in breast cancer. Rachner TD et al., Breast Cancer Res Treat. 2020; 180(2):515-524.
5. Development of an engineered peptide antagonist against periostin to overcome doxorubicin resistance in breast cancer. Oo KK, Kamolhan T, Soni A, Thongchot S, Mitrpant C, O-Charoenrat P, Thuwajit C, Thuwajit P. BMC Cancer. 2021; 14;21(1):65. doi: 10.1186/s12885-020-07761-w.
6. Neuropilin1, a novel independent prognostic factor and therapeutic target in triple-negative breast cancer. Wang H, Zhang YN, Xu DQ, Huang JG, Lv D, Shi XY, Liu JY, Ren HW, Han ZX. Neoplasma. 2020; 67(6):1335-1342. doi: 10.4149/neo_2020_191127N1223. PMID: 32657612.
7. Neuropilin-1 is over-expressed in claudin-low breast cancer and promotes tumor progression through acquisition of stem cell characteristics and RAS/MAPK pathway activation. Tang YH, Rockstroh A, Sokolowski KA, Lynam LR, Lehman M, Thompson EW, Gregory PA, Nelson CC, Volpert M, Hollier BG. Breast Cancer Res. 2022; 25;24(1):8. doi: 10.1186/s13058-022-01501-7. PMID: 35078508.
8. Endothelial VEGFR Coreceptors Neuropilin-1 and Neuropilin-2 Are Essential for Tumor Angiogenesis. Benwell CJ, Johnson RT, Taylor JAGE, Price CA, Robinson SD. Cancer Res Commun. 2022 Dec 14;2(12):1626-1640. doi: 10.1158/2767-9764.CRC-22-0250. PMID: 36970722; PMCID: PMC10036134.
9. Neuropilin-1 expression is associated with lymph node metastasis in breast cancer tissues. Seifi-Alan M, Shams R, Bandehpour M, Mirfakhraie R, Ghafouri-Fard S. Cancer Manag Res. 2018 Jul 11;10:1969-1974. doi: 10.2147/CMAR.S169533. PMID: 30022855; PMCID: PMC6045910.
10. Soluble Neuropilin-1 is an independent marker of poor prognosis in early breast cancer. Rachner TD, Kasimir-Bauer S, Goebel A, Erdmann K, Hoffmann O, Rauner M, Hofbauer LC, Kimmig R, Bittner AK. J Cancer Res Clin Oncol. 2021; 147(8):2233-2238. doi: 10.1007/s00432-021-03635-1. PMID: 33884469.
11. Neuropilin-1 as a Potential Biomarker of Prognosis and Invasive-Related Parameters in Liver and Colorectal Cancer: A Systematic Review and Meta-Analysis of Human Studies. Fernández-Palanca P, Payo-Serafín T, Fondevila F, Méndez-Blanco C, San-Miguel B, Romero MR, Tuñón MJ, Marin JJG, González-Gallego J, Mauriz JL. Cancers (Basel). 2022 Jul 15;14(14):3455. doi: 10.3390/cancers14143455. PMID: 35884516.
12. SPECT and near-infrared fluorescence imaging of breast cancer with a neuropilin-1-targeting peptide. Feng GK, Liu RB, Zhang MQ, Ye XX, Zhong Q, Xia YF, Li MZ, Wang J, Song EW, Zhang X, Wu ZZ, Zeng MS.J Control Release. 2014; 28;192:236-42. doi: 10.1016/j.jconrel.2014.07.039. PMID: 25058570.
13. Semaphorin 4D as a guidance molecule in the immune system. Kuklina E. Int Rev Immunol. 2021;40(4):268-273. doi: 10.1080/08830185.2021.1905807. PMID: 33787446.
14. The role of semaphorin 4D in tumor development and angiogenesis in human breast cancer. Jiang H, Chen C, Sun Q, Wu J, Qiu L, Gao C, Liu W, Yang J, Jun N, Dong J. Onco Targets Ther. 2016 Sep 26;9:5737-5750. doi: 10.2147/OTT.S114708. PMID: 27729799; PMCID: PMC5045906.
15. Semaphorin 4D Promotes Skeletal Metastasis in Breast Cancer. Yang YH, Buhamrah A, Schneider A, Lin YL, Zhou H, Bugshan A, Basile JR.PLoS One. 2016; 11(2):e0150151. doi: 10.1371/journal.pone.0150151. PMID: 26910109.
16. Reduced expression of semaphorin 4D and plexin-B in breast cancer is associated with poorer prognosis and the potential linkage with oestrogen receptor. Malik MF, Ye L, Jiang WG. Oncol Rep. 2015 Aug;34(2):1049-57. doi: 10.3892/or.2015.4015. Epub 2015 May 28. PMID: 26035216.
17. Plasma levels of Semaphorin 4D are decreased by adjuvant tamoxifen but not aromatase inhibitor therapy in breast cancer patients. Göbel, A., Kuhlmann, J.D., Link, T., Wimberger, P., Link-Rachner, C., Thiele, S., Dell’Endice, S., Furesi, G., Breining, D., Rauner, M., Hofbauer, L.C., Rachner, T.D., 2019. Journal of Bone Oncology, 16: 100237. PMID: 31011525
18. Semaphorin4D Inhibition Improves Response to Immune-Checkpoint Blockade via Attenuation of MDSC Recruitment and Function. Clavijo PE, Friedman J, Robbins Y, Moore EC, Smith E, Zauderer M, Evans EE, Allen CT. Cancer Immunol Res. 2019; 7(2):282-291. doi: 10.1158/2326-6066.CIR-18-0156. PMID: 30514791.

Leucine-rich alpha-2-glycoprotein (LRG or syn. LRG1) is a glycoprotein that has gained attention in the context of various cancers, including breast cancer. It is encoded by the LRG1 gene and is known for its role in the immune response and its involvement in various biological processes, including inflammation and tissue repair (1, 2).

In patients diagnosed with early breast cancer (BC), elevated levels of intratumoral LRG-1 protein expression are linked to decreased survival rates (3). In a recent study by Göbel A et al., serum LRG-1 levels were assessed in 509 patients with primary early BC (4). The study explored the correlation of LRG with the presence of disseminated tumor cells (DTCs) in the bone marrow as well as survival outcomes.

LRG-1 a prognostic marker for breast cancer survival

The LRG ELISA assay from BIOMEDICa has been utilized in this study (4) demonstrating that serum levels of leucine-rich α-2 glycoprotein serve as an independent prognostic indicator for breast cancer-specific survival. This discovery could lead to novel diagnostic approaches, particularly given that serum sample analyses in cancer patients are readily available, cost-effective, and can be easily integrated into standard clinical practices.

High serum levels of leucine-rich α-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer. Göbel A,et al., Arch Gynecol Obstet 2024; 309(6):2789-2798. 

 

ROLE OF LRG-1 in BREAST CANCER

Biomarker Potential: LRG has been investigated as a potential biomarker for breast cancer. Studies have indicated that LRG levels is elevated in the serum of breast cancer patients compared to healthy controls (4). This suggests that LRG could potentially be used as a diagnostic or prognostic marker, providing insights into disease presence and progression. 

Tumor Microenvironment: LRG is thought to play a role in modulating the tumor microenvironment. It may influence the behavior of cancer cells and the surrounding stromal cells, thereby impacting tumor growth and metastasis. Its interactions with various cytokines and immune cells can affect inflammation and immune evasion, which are critical components of cancer progression.

Mechanisms of Action: The exact mechanisms by which LRG influences breast cancer are still being unraveled. There is evidence suggesting that LRG can modulate the signaling pathways involved in cancer cell proliferation and survival. Its leucine-rich regions are known to interact with a variety of proteins, possibly contributing to the malignancy of breast cancer cells.

Therapeutic Implications: Given its involvement in tumor progression and immune regulation, LRG is being explored as a potential therapeutic target. Strategies aimed at modulating LRG levels or blocking its actions could offer new avenues for treatment, particularly in patients with aggressive or metastatic breast cancer.

Research Directions: Ongoing research is focused on further elucidating the role of LRG in breast cancer. This includes understanding its function in different breast cancer subtypes (e.g., triple-negative breast cancer) and its interactions within the immune system. The potential for LRG to serve as a target for immunotherapy or be a part of combination therapies is also an area of ongoing investigation.

Conclusion: LRG is emerging as an important player in the context of breast cancer, both as a potential biomarker and as a target for therapeutic interventions. While more research is needed to fully understand its role and mechanisms, the current findings highlight its significance in the pathophysiology of breast cancer and its potential utility in improving cancer diagnosis and treatment outcomes. The continued exploration of LRG may pave the way for advancements in personalized medicine strategies for breast cancer patients.

LRG ELISA Assay Highlights (cat. no. BI-LRG)

• SPECIFIC – characterized antibodies – epitope mapped
• CONVENIENT – ready to use reagents and controls included
• RELIABLE – rigorously validated following international quality guidelines
• EASY – results available in 3 hours
• Protocol booklet, instructions for use- click here

 

For detailed information please click on the link: Leucine-rich alpha-2-glycoprotein (LRG) ELISA | BI-LRG

Literature

1. Research Progress on Leucine-Rich Alpha-2 Glycoprotein 1: A Review. Zou Y, Xu Y, Chen X, Wu Y, Fu L, Lv Y. Front Pharmacol. 2022 Jan 5;12:809225. doi: 10.3389/fphar.2021.809225. PMID: 35095520; PMCID: PMC8797156.
2. Intracellular leucine-rich alpha-2-glycoprotein-1 competes with Apaf-1 for binding cytochrome c in protecting MCF-7 breast cancer cells from apoptosis. Jemmerson R, Staskus K, Higgins L, Conklin K, Kelekar A Apoptosis. 2021 Feb;26(1-2):71-82. doi: 10.1007/s10495-020-01647-9. PMID: 33386492; PMCID: PMC7904597.
3. The role of leucine-rich alpha-2-glycoprotein-1 in proliferation, migration, and invasion of tumors. Lin M, Liu J, Zhang F, Qi G, Tao S, Fan W, Chen M, Ding K, Zhou F. J Cancer Res Clin Oncol. 2022 Feb;148(2):283-291. doi: 10.1007/s00432-021-03876-0. PMID: 35037101.
4. High serum levels of leucine-rich α-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer. Göbel A, Rachner TD, Hoffmann O, Klotz DM, Kasimir-Bauer S, Kimmig R, Hofbauer LC, Bittner AK.Arch Gynecol Obstet. 2024 Jun;309(6):2789-2798. doi: 10.1007/s00404-024-07434-0. PMID: 38413424; PMCID: PMC11147863.

 

Breast Cancer Awareness Month is a global health initiative celebrated every October. Its purpose is to raise awareness about screening and prevention for a disease that impacts 2.3 million women worldwide.

Breast cancer (BC) is the most prevalent cancer among women and ranks as the most common cancer overall. While it predominantly affects women, men can also develop breast tissue that becomes malignant. Male breast cancers are uncommon, accounting for only 1% of all cases, yet men are frequently diagnosed at more advanced stages. This delay in seeking medical care often leads to later presentations and poorer outcomes.

Breast Cancer Awareness Month – October 2024

Several risk factors can increase the likelihood of developing breast cancer, including:

• Gender: Being female is the primary risk factor.
• Age: The risk increases with age, particularly for women over 55.
• Family History: Genetics can play a role; individuals with a family history of breast cancer may have mutations in genes such as BRCA1 and BRCA2.
• Personal History: Those who have had breast cancer or certain benign breast conditions are at a higher risk.
• Lifestyle Factors: Factors such as obesity, lack of physical activity, alcohol consumption, and smoking can contribute to the risk.

 

Early detection through regular screening improves outcomes significantly. The prognosis for breast cancer varies significantly depending on several factors, including the type of cancer, the stage at diagnosis, and how well the cancer responds to treatment.

Prevention and Awareness

While it’s not possible to prevent breast cancer entirely, certain lifestyle choices can help reduce risk, such as maintaining a healthy weight, exercising regularly, moderating alcohol intake, and avoiding tobacco. Organizations worldwide promote Breast Cancer Awareness Month in October, highlighting the importance of early detection, education, and support resources for those affected by the disease.

Further reading

• Breast Cancer Screening and Prevention. Farkas AH, Nattinger AB. Ann Intern Med. 2023 Nov;176(11):ITC161-ITC176. doi: 10.7326/AITC202311210. Epub 2023 Nov 14. PMID: 37956433.

 

• Breast cancer highlights from 2023: Knowledge to guide practice and future research. Cardoso MJ, Poortmans P, Senkus E, Gentilini OD, Houssami N.Breast. 2024 Apr;74:103674. doi: 10.1016/j.breast.2024.103674. Epub 2024 Jan 27. PMID: 38340683; PMCID: PMC10869942.

 

• Male Breast Cancer (MBC) – A Review. AlFehaid M. Pol Przegl Chir. 2023 Dec 30;95(6):24-30. PMID: 38058163.

 

Biomedica´s Oncology Product Line

 

Join us at the ASBMR (American Society of Bone and Mineral Research) Conference at booth number 145. The annual meeting is taking place in Toronto, ON, Canada from September 27-30, 2024.

The American Society of Bone and Mineral Research (ASBMR) meeting is considered to be the largest event worldwide covering fields in bone, mineral and musculoskeletal research. The meeting attracts over 2,500 participants across the globe, including both clinicians and researchers working in different disciplines and at all career levels. The meeting provides attendees with exciting opportunities to exchange knowledge and to learn about the latest scientific and medical advances in the field.

Discover some of our biomarker assays for clinical research in bone and mineral disorders

–FGF23 intact and c-terminal

–Sclerostin and bioactive Sclerostin

–Osteoprotegerin(OPG)  and soluble RANKL

–Dickkopf-1 and Periostin

 

 

Exploring Biomarkers in Bone Biology

During the process of bone remodeling, bone cells release biomarkers that can aid in the evaluation of bone diseases and serve as valuable therapeutic targets. These bone biomarkers can be readily detected in serum and plasma samples using immunoassays.

A recent review by Nicolas H Hart et al., provides researchers and clinicians involved in bone and mineral metabolism with a comprehensive contemporary update on the Biological basis of bone strength: anatomy, physiology and measurement. J Musculoskelet Neuronal Interact. 2020; ;20(3):347-371.

Abstract

Understanding how bones are innately designed, robustly developed and delicately maintained through intricate anatomical features and physiological processes across the lifespan is vital to inform our assessment of normal bone health, and essential to aid our interpretation of adverse clinical outcomes affecting bone through primary or secondary causes. Accordingly this review serves to introduce new researchers and clinicians engaging with bone and mineral metabolism, and provide a contemporary update for established researchers or clinicians. Specifically, we describe the mechanical and non-mechanical functions of the skeleton; its multidimensional and hierarchical anatomy (macroscopic, microscopic, organic, inorganic, woven and lamellar features); its cellular and hormonal physiology (deterministic and homeostatic processes that govern and regulate bone); and processes of mechanotransduction, modelling, remodelling and degradation that underpin bone adaptation or maladaptation. In addition, we also explore commonly used methods for measuring bone metabolic activity or material features (imaging or biochemical markers) together with their limitations.

 

 

 

September is Blood Cancer Awareness Month raising awareness about the various types of blood cancers, including leukemia, lymphoma, myeloma, and other hematologic malignancies. The goal of this month-long initiative is to educate the public about the signs, symptoms, and the risks that are associated with these cancers, as well as the importance of early detection and treatment.

Some cancer treatments may lead to bone loss and increases the risk of osteoporosis and fractures. Learn more about the impact of intensive chemotherapy and glucocorticoid treatment on bone remodeling markers in children with acute lymphoblastic leukemia in the study described below (1).

The campaign also focuses on highlighting the latest advancements in blood cancer research and treatment, emphasizing that ongoing research is essential for improved outcomes and quality of life for patients.

September is Blood Cancer Awareness Month

Acute lymphoblastic leukemia (ALL) is a type of cancer that affects the blood and bone marrow. ALL is the most common cancer in children. Intensive chemotherapy has improved the 5-year survival rate for ALL patients up to 90%. However, this improved survival has resulted in long-term complications associated with chemotherapy, including negative effects on bone health including osteopenia/osteoporosis, osteonecrosis, and increased fragility fractures.

Skeletal health relies on a balance between bone resorption and bone formation

The health of the skeleton relies on a balance between bone resorption and bone formation, a process known as “bone remodeling,” which is regulated by the RANKL/RANK/osteoprotegerin (OPG) and Wnt/β-catenin signaling pathways.

Currently, there is a lack of data regarding the impact of intensive chemotherapy on bone remodeling markers in children with ALL. In a recent study, researchers in Italy investigated the role of bone remodeling markers in children with acute lymphoblastic leukemia after intensive chemotherapy and glucocorticoid (GC) treatment (1). The bone remodeling markers such as RANKL, OPG and the WNT signaling molecules Sclerostin and DKK-1 were also measured with ELISA kits from BIOMEDICA.

The researchers found “higher levels of RANKL and OPG in ALL children compared to the controls, with a balance of RANKL/OPG ratio, whereas the levels of sclerostin and DKK-1, the main inhibitors of osteoblastogenesis, were similar in the two groups of subjects. These results suggest that in our cohort of ALL subjects, the intensive chemotherapy and GCs increased osteoclastic activity and, thereby, bone resorption” (1).

About the RANK/RANKL/OPG system

The receptor-ligand duo, RANK and RANKL are crucial regulators of bone metabolism and osteoclast development. Osteoprotegerin (OPG) acts as a decoy receptor for RANKL. It competitively binds to RANKL and interferes with the interaction of RANKL–RANK, thus blocking bone resorption. Beyond its role as a regulator of bone remodeling, the RANK/RANKL/OPG system has direct effects on the development of tumor cells, as it is implicated in the progression of breast and prostate cancer as well as leukemia.

About the WNT signaling molecules Sclerostin and DKK-1

Sclerostin (SOST) is mainly produced by osteocytes and is considered as the major regulator of bone formation. It is a soluble antagonist of the Wnt signaling pathway. Inactivating this pathway leads to bone degradation, while induction of Wnt signaling promotes bone formation.

Dickkopf-1 (DKK-1) is an extracellular protein. DKK-1 plays a role in the regulation of bone metabolism, and is a secreted inhibitor of the Wnt signaling pathway. DKK-1 inhibits the differentiation of osteoblasts and thereby bone formation. The dysregulation of DKK1 can lead to cancer progression.  

Biomedica offers quality kits for the measurement of these bone biomarkers

-Osteoprotegerin (OPG) ELISA (cat. no. BI-20403)

-Soluble free RANKL ELISA (cat. no. BI-20462)

-Sclerostin (SOST) ELISA (cat.no. BI-20492)

-Bioactive Sclerostin (SOST) ELISA (cat. no. BI-20472)

-DKK-1 (Dickkopf-1) ELISA (cat.no. BI-20413)

 

• Widely cited in + 1000 publications
• Validated kits following international quality guidelines

 

Literature

1. Bone Remodeling Markers in Children with Acute Lymphoblastic Leukemia after Intensive Chemotherapy: The Screenshot of a Biochemical Signature. Muggeo P, Grassi M, D’Ascanio V, Brescia V, Fontana A, Piacente L, Di Serio F, Giordano P, Faienza MF, Santoro N. Cancers (Basel). 2023 Apr 29;15(9):2554. doi: 10.3390/cancers15092554. PMID: 37174020; PMCID: PMC10177249.
2. The RANK-RANKL-OPG System: A Multifaceted Regulator of Homeostasis, Immunity, and Cancer. Medicina (Kaunas). De Leon-Oliva D, Barrena-Blázquez S, Jiménez-Álvarez L, Fraile-Martinez O, García-Montero C, López-González L, Torres-Carranza D, García-Puente LM, Carranza ST, Álvarez-Mon MÁ, Álvarez-Mon M, Diaz R, Ortega MA. 2023 Sep 30;59(10):1752. doi: 10.3390/medicina59101752. PMID: 37893470; PMCID: PMC10608105.
3. Understanding the Wnt Signaling Pathway in Acute Myeloid Leukemia Stem Cells: A Feasible Key against Relapses. Biology (Basel). Láinez-González D, Alonso-Aguado AB, Alonso-Dominguez JM. 2023 May 5;12(5):683. doi: 10.3390/biology12050683. PMID: 37237497; PMCID: PMC10215262.

Lyme disease is a bacterial infection that is spread to humans by infected ticks. It is also known as Lyme Borrelioses caused by the borrelia bacteria. Symptoms often include fever, headache, fatigue, and an expanding skin rash.  If left untreated, the infection can spread to various parts of the body, affecting joint, heart, and the nervous system.

Lyme disease is the most common vector-borne disease in temperate zones of the northern hemisphere (1-3).

Early diagnosis and treatment are essential for effectively managing Lyme Borreliosis.

Serologic Testing for Lyme Disease

BIOMEDICA offers sensitive and specific ELISA Assay Kits for the quantitative determination of Borrelia IgG and IgM antibodies in human serum, plasma and cerebrospinal fluid.

Our BORRELIA  Enzyme immunoassays utilize recombinant antigens for the detection of IgG and IgM antibodies against the immunodominent antigens of the three genospecies: Borrelia burgdorferi sensu stricto, Borrelia afzelii and Borrelia garinii.

Borrelia IgG ELISA | BI-21032 

The use of recombinant Antigens offers the following advantages

• High sensitivity and specificity confirmed by clinical samples
• Standardized protocols for serum, plasma, CSF
• For manual and automated testing
• CE -marked for IVD use in the EU
• Widely cited

 

OF NOTE:

To improve the diagnostic specifity, the Biomedica Borrelia IgG ELISA microwell strips are coated with the following recombinant antigens:

• p21 = OspC (outer surface protein C): B. burgdorferi sensu stricto (B31), B. garinii (20047)
• p18: B. afzelii (pKo)
• p100: B. afzelii (pKo)
• VIsE: fusion protein of different Borrelia genospecies

 

Borrelia IgM ELISA | BI-21042

The use of recombinant Antigens offers the following advantages

• No extra RF stripping necessary
• High sensitivity and specificity confirmed by clinical samples
• Standardized protocols for serum, plasma, CSF
• For manual and automated testing
• CE -marked for IVD use in the EU
• Widely cited

 

OF NOTE:

To improve the diagnostic specifity, the Biomedica Borrelia IgM ELISA microwell strips are coated with the following recombinant antigens:

• p21 = OspC (outer surface protein C): B. afzellii (pKo)
• p21 = OspC (outer surface protein C): B. garinii (20047)
• p41/I = (inner part of flagellin): B. bavariensis (pBi)
• VIsE: fusion proteins of different Borrelia genospecies 

 

Literature

1. Lyme Disease Pathogenesis. Coburn J, Garcia B, Hu LT, Jewett MW, Kraiczy P, Norris SJ, Skare J. Curr Issues Mol Biol. 2021;42:473-518. doi: 10.21775/cimb.042.473. PMID: 33353871.
2. A Comprehensive Review of Lyme Disease: A Focus on Cardiovascular Manifestations. Wu M, Mirkin S, McPhail MN, Wajeeh H, Nagy S, Florent-Carre M, Blavo C, Demory Beckler M, Amini K, Kesselman MM. Cureus. 2024 May 21;16(5):e60821. doi: 10.7759/cureus.60821. PMID: 38910626; PMCID: PMC11190629.
3. The Epidemiology of Lyme Borreliosis in Europe: An Updated Review on a Growing Public Health Issue. Stark JH, Pilz A, Jodar L, Moïsi JC.Vector Borne Zoonotic Dis. 2023;23(4):139-141. doi: 10.1089/vbz.2022.0068. PMID: 37071398.

 

 

The “EZ4U assay cell viability assay” was highlighted in a recent study investigating the effects of RNA modifications (m⁶A demethylases) on renal cell carcinoma cell lines. Accumulating evidence shows that m⁶A RNA methylation participates in the pathogenesis of multiple diseases including cancers. 

Renal cell carcinoma (RCC) accounts for approximately 3% of all cancers in adults. The 5-year survival rate for patients with locally advanced or metastatic RCC is poor with a prognosis of approximately 5%. Despite advanced pharmacological treatments of these patients (e.g. checkpoint immunotherapy, anti-VEGF antibodies, tyrosine kinase inhibitors), patient survival rates have only moderately improved.

Epigenetics studies the modification of heritable gene expression without having changes in the DNA sequence (1). N⁶-methyladenosine (m6A) is a common post-transcriptional methylation occurring in different types of RNAs in eukaryotic cells (2). m6A methylation is important in a number of physiological processes including the response to DNA damage. Recent studies suggest that RNA methylation has a great impact in cancer development and may provide a novel target for cancer treatment (3).

In a recent study researchers investigated the effects of RNA modifications (m⁶A demethylases) on renal cell carcinoma cell lines (4). Cell viability was determined with the BIOMEDICA EZ4U (easy for you) assay. In brief, cells were incubated with the EZ4U substrate for 3 hours at 37°C and absorbance was measured at 450 nm with 620 nm as reference.

Measuring Cell Viability with the EZ4U (MTT) Assay (developed and manufactured by Biomedica)

The EZ4U (easy for you) assay is a metabolic assay (similar to the MTT assay) that can quantify cell health. It measures the  reduction of the colorimetric substrate through the activity of mitochondrial enzymes in the cells.

Assays measuring cell viability are a widely used tool in cell biology research. The EZ4U test kit is a straightforward and reliable non-radioactive assay that is completed within two to five hours, depending on the cell type studied. The EZ4U assay employs non-toxic tetrazolium salts, which are, during incubation, converted into colored formazan. As the reduction process relies on functional mitochondria that become inactive shortly after cell death, this method effectively distinguishes between living and dead cells. The assay procedure is identical to the thymidine incorporation procedure. Therefore, no changes in test protocols are necessary. Furthermore, an additional benefit is the ability to continue cultivation after determining cell numbers.

The EZ4U cell proliferation and cytotoxicity assay is highly suited for testing cell viability in a number of different cell types. The assay has been used in various cell types and citations can be found in the link.

EZ4U Cell Proliferation and  Cytotoxicity Assay –single incubation step using living cells

Brief description: 20µl of the EZ4U substance (colorless non-toxic tetrazolium salts) is first added to each well. The mitochondria of the living cells oxidize the EZ4U substance to a yellow-colored formazan derivate. The color change is measured on a conventional plate reader at 450 nm using a reference wavelength of 620 nm.

EZ4U  Cell Viability & Cytotoxicity Assay (cat.no. BI-5000)

• Reliable & Sensitive
• One step incubation  – for use on living cells
• Widely used – referenced in +270 publications

 

Download the BROCHURE – EZ4U cell proliferation and cytotoxicity assay and the PROTOCOL BOOKLET

Literature

1. The role of m6A modification in the biological functions and diseases. Jiang X et al., Signal Transduct Target Ther. 2021; 21;6(1):74. PMID: 33611339.
2. Depletion of the m⁶A demethylases FTO and ALKBH5 impairs growth and metastatic capacity through EMT phenotype change in clear cell renal cell carcinoma. Hu W et al., Am J Transl Res. 2023; 15(3):1744-1755. PMID: 37056835.
3. The potential role of RNA N6-methyladenosine in Cancer progression. Wang T et al., Mol Cancer. 2020. 19(1):88. PMID: 32398132.
4. Depletion of the m⁶A demethylases FTO and ALKBH5 impairs growth and metastatic capacity through EMT phenotype change in clear cell renal cell carcinoma. Hu W Am J Transl Res. 2023 Mar 15;15(3):1744-1755. PMID: 37056835.

 

ELISA (Enzyme Linked Immunosorbent Assay) tests are one of the most used biomedical methods for quantifying analytes in biological samples. Apart from their sensitivity and specificity, they are characterized by their simplicity and cost-effectiveness compared to many other analytical methods. However, the easiness in performing an ELISA assay may mask some of the more complex aspects when measuring biological samples.

One of the most common ELISA techniques is the Sandwich ELISA which is used to measure the amount of antigen between two layers of antibodies. Sandwich ELISAs have the limitation that the antigen (e.g. protein in the sample) must have at least two antigen binding sites so that at least two different antibodies can bind. However, these assays are useful when the concentration of the antigen in the sample is low or high concentrations of other antigens contaminate a sample.

Principle of a Sandwich ELISA Assay

Typically a 96-well microtiter plate is pre-coated with a specific “capture antibody” (monoclonal or polyclonal antibody). After adding the sample to the microtiter plate and during an incubation period, the protein of interest present in the sample binds to the pre-coated antibody in the well. Next, the “detection antibody” is added to the well, which forms a sandwich (capture antibody – target antigen – detection antibody).

Figure 1: ELISA Assay Principle 

 

The results can be quantified by adding an enzyme conjugated antibody specific for the second epitope, catalyzing an enzymatic color reaction. The amount of bound enzyme conjugate in the well is detected after following a short incubation with an appropriate substrate. The resulting signal (color change in the well) is detectable with a standard microtiter plate ELISA reader measuring the absorbance (optical density) – the greater the signal, the greater the concentration of the analyte in the sample that is measured throughout the range of the standard curve.

Figure 2: Typical standard curve (using 7 calibrators) for a sandwich ELISA assay, showing the relation between the signal and the analyte concentration 

 

How to Obtain Reproducible ELISA Assay Results

To obtain reliable results it is recommended to choose an ELISA Assay that has gone through a full validation protocol. Results (validation data) must be provided that include data on specificity, sensitivity (LOD, LLOQ), accuracy/recovery, parallelism and dilution linearity, precision (within-run and in-between run), calibration, stability, and lot-to-lot consistency.

CORNERSTONES OF AN ELISA ASSAY VALIDATION

1.SPECIFICITY

Ensuring accurate measurement of the protein of interest

The performance of an ELISA is linked to the quality of the antibody pairs used for the analyte/biomarker detection.

The supplier (assay developer ) needs to :

-select antibody pairs with high affinity and specificity with mapped binding sites

-optimize the ELISA kits to quantify biomarkers in both healthy and pathological samples

 

2.SENSITIVITY

Enabling the detection of low levels of the analyte of interest

The sensitivity of an ELISA assay refers to the lowest limit of detection (LOD) of the protein that can be detected with the antibody pair used in the ELISA kit. The sensitivity depends mainly on the affinity of the solid phase antibody (coating antibody). Therefore, using a high affinity antibody can increase sensitivity.

-Analytical sensitivity – limit of detection (LOD) is the lowest concentration that can be measured (detected) with statistical significance by means of a given analytical procedure. This concentration is calculated as the background +/- 2 standard deviations.

-Functional Sensitivity –  lower limit of detection (LLOQ) is the lowest concentration at which the analyte can be reliably detected.

 

3.ACCURACY / RECOVERY

Ensuring the correct presence or absence of the protein of interest in samples with different matrices (serum, plasma)

The accuracy in an ELISA assay correctly identifies the presence or absence of the target protein / antigen (biomarker of interest) in a specific sample, which excludes matrix effects that may interfere with the measurement of the analyte of interest.

-Ideally, the accuracy should be determined in all of the sample types (e.g. serum, EDTA plasma, heparin plasma..) where the analyte of interest will be measured. For this reason, the various sample matrices are spiked with known amounts of the recombinant analyte. Samples are analysed against the standard/calibration curve of the assay and then compared with the nominal value.

 

4.PARALLELISM / DILUTION LINEARITY

Ensuring that samples can be measured with confidence / Ensuring that serial dilutions of samples are quantitated accurately

-Parallelism determines whether real samples with high endogenous analyte concentrations yield the same level of detection in the standard curve after sample dilution. This procedure highlights differences in the binding affinity of the antibodies to the endogenous analyte and the analyte used for calibrating the ELISA.  Parallelism in real samples containing endogenous levels of the analyte should always be tested during assay validation.

-Dilution linearity determines the recovery of the analyte in samples that are spiked with the recombinant analyte, used for calibrating the assay (standards).

 

5.PRECISION

Ensuring precise and consistent results within and across lots

-Within-run precision (repeatability) – evaluation of the precision of the ELISA that measures the variation between multiple determinations of one sample in one single test run.

-In-between run precision – evaluation of samples that are tested several times within one ELISA assay lot guaranteeing accurate results when using ELISA kits that derive from different kit lots.

 

6.CALIBRATION

Enabling the accurate quantification of the protein of interest

-The accurate quantification depends on the linearity and the reproducibility of the standard curve. During the optimization process of the ELISA kit, low variability between the results of the calibrators must be ensured. Whenever available, standard calibration with standards calibrated to NIBSC standards or WHO reference should be employed to ensure a harmonized standardization.

 

7.STABILITY

Enabling stability of the analyte of interest in respective samples as well as the stability of the reagents in the ELISA kit

During development, stability of all assay components as well as the stability of the analyte of interest in the respective sample matrices (serum, plasma) should be tested.

-The stability of the analyte can be tested in samples when e.g. samples undergo repeated freeze-thaw cycles or if samples are exposed to room-temperature for a prolonged (defined) period of time. 

-Assay kit stabilty (e.g. stability of the kit reagents) should be tested at various temperature settings for a defined period of time.

-Shelf-life of the kit: the real-time stabilty of kit reagents should be tested during the shelf life of the kit. e.g. when kit reagents are stored at 4°C  for 6/12/18 months.

 

8.LOT-TO-LOT CONSISTENCY

Ensuring that consistent results are obtained with different ELISA kit lots

The use of “in-house controls” (serum and plasma samples) containing the endogenous analyte as well as samples that are spiked with the recombinant analyte are tested in every kit lot batch to evaluate whether the data are within the set quality control ranges.

How to Obtain Reproducible ELISA Assay Results

• BIOMEDICA´s ELISA kits undergo a full validation following international quality guidelines making sure that your precious samples only detect the analyte of interest.

 

Learn more about how to obtain reproducible ELISA assay results by clicking on the link:

https://www.bmgrp.com/quality  

 

WHY CHOOSE ELISA KITS from BIOMEDICA? 

Specific – accurate biomarker detection with characterized antibodies

Reliable –validation using clinical samples

Reproducible – guaranteed lot to lot consistency

 

Further reading

A Practical Guide to Immunoassay Method Validation. Andreasson Uet al., Front Neurol. 2015 Aug 19;6:179. doi: 10.3389/fneur.2015.00179. PMID: 26347708; PMCID: PMC4541289.

 

IL-6 (Interleukin-6) is a protein that acts both as a pro-inflammatory cytokine and as an anti-inflammatory myokine (1). During physical activity, IL-6 is released from muscle fibers into the bloodstream where it has different functions:

–Energy Balance: IL-6 is a regulator of energy metabolism. It promotes the breakdown of fats and stimulates glucose production, thus ensuring that muscles have a constant energy supply during prolonged exercise.

–Anti-inflammatory effects: Although IL-6 is an immunoregulatory molecule that promotes inflammation in certain contexts, IL-6 also has anti-inflammatory properties during exercise. It stimulates the production of anti-inflammatory cytokines and inhibits the production of pro-inflammatory cytokines, reducing overall inflammation in the body.

–Muscle repair: IL-6 activates pathways that contribute to muscle regeneration and adaptation, thus helping muscles to recover and become stronger after physical activity.

Interleukin-6 (IL-6) and Exercise

The efficacy of exercise to reverse frailty in an aging population has been investigated in a randomized controlled trial (2). The study investigated the effectiveness of a multicomponent exercise program (MCEP) in older adults that also included the measurement of blood biomarkers Interleukin-6 (IL-6) and C-reactive protein (CRP). The results clearly indicate that when compared with controls at 12-weeks, the MCEP group significantly showed a decrease in IL-6 and CRP levels (p < 0.05). In conclusion, the study clearly demonstrated that the MCEP exercise program was effective in improving physical performance and quality of life. Further, it delays frailty and decreases inflammation in frail older adults (2).  

IL-6 can easily be measured in various biological fluids with a conventional ELISA assay.

Human IL-6 ELISA (cat. no. BI-IL6)

• HIGH SENSITIVITY – detectable  values in serum and plasma samples
• RELIABLE – full validation
• CONVENIENT – ready to use calibrators and controls
• PROMOTION – Take 15% off!

 

IL-6 ELISA ASSAY CHARACTERISTICS (#BI-IL6)

• Method: Sandwich ELISA, HRP/TMB, 12×8-well detachable strips
• Sample type: Plasma (EDTA, citrate, heparin), serum, cell culture, and urine
• Sample volume / well: 100 µl
• Incubation: 2 h / 1 h / 1 h / 30 min
• Sensitivity:  0.28 pg/ml (LLOQ: 0.78 pg/ml (measurable concentrations in serum AND plasma samples)
• Assay range: 0 – 200 pg/ml (ready standards with concentrations at: 0 /3.12 / 6.25 / 12.5 / 25 / 25 / 50 /100 /200 pg/ml)  
• Precision: In-between-run (n=3): ≤ 6 % CV, within-run (n=3): ≤ 7 % CV
• Specificity: The human IL-6 ELISA recognizes recombinant and endogenous (natural human IL-6)
• Validation data: precision, accuracy, dilution linearity, parallelism, values for healthy donors are shown here
• Use: research use only

 

Literature

1. Interleukin-6 myokine signaling in skeletal muscle: a double-edged sword? Muñoz-Cánoves Pet al., FEBS J. 2013; 280(17):4131-48. doi: 10.1111/febs.12338.
2. Multicomponent Exercise Program Reduces Frailty and Inflammatory Biomarkers and Improves Physical Performance in Community-Dwelling Older Adults: A Randomized Controlled Trial. Sadjapong U et al., Int J Environ Res Public Health. 2020; 7(11):3760. doi: 10.3390/ijerph17113760.

 

We are present in over 60 countries, ensuring global availability and customer support through partnerships with selected local distributors on almost every continent. Regardless of your location, we are here to help you reach your goals.

With over 30 years of experience, we specialize in developing and manufacturing high-quality ELISA assay kits for biomarkers in clinical research.

Check out our ELISA Assay product brochure

Our ELISA Kits Travel Worldwide – contact us or your local representative 

About us

BIOMEDICA develops and manufactures high quality and widely cited immunoassays for clinical and pre-clinical applications in bone and cardiorenal diseases. For specific biomarkers, Biomedica has become a world-wide leader, e.g. Sclerostin, free sRANKL, OPG, DKK-1, and NT-proCNP.   

All Biomedica ELISA assays are fully validated following international quality guidelines. The assays include ready-to-use serum-based calibrators and controls enabling researchers to collect biologically reliable data.

This year’s ELISA assay highlights  

Cardiac Safety Biomarkers : Rat NT-proBNP, NT-proANP ELISA kits

FGF23  : FGF23 intact , FGF23 (C-terminal) ELISA kits

Cytokines  : VEGF, Angiopoietin-2, IL-6   

Discover our PROMOTION : Take 15% OFF of the human IL-6 ELISA Assay now through end of 2024! Making IL-6 ELISA Kits more affordable!

 

Features & Benefits of BIOMEDICA ELISA Assay Kits

• Highly Specific – many of our kits employ  characterized epitope-mapped antibodies
• Excellent Quality – our kits are validated according to international quality guidelines (ICH, FDA..)
• Convenient Use  –offering ready to use and color coded reagents – controls are included in all kits! 

 

Other Products

EZ4U – Cell Proliferation & Cytotoxicity Assay (cat. no. BI-5000) for reliable testing of cell viability in 96-well microtiter plates.

 Features & Benefits EZ4U Assay

-easy and convenient singe-step incubation for use on living cells

-non-radioactive

-cultivation can be continued after cell numbers are determined

-widely cited in more than 240 publications e.g.

• BRD4-targeting PROTACs Synergize With Chemotherapeutics Against Osteosarcoma Cell Lines
  Lang et al., Anticancer Res; 2024; 44 (3), 971-980.  PMID: 38423674
• Expression of cytokines in pleural effusions and corresponding cell lines of small cell lung cancer
  Rath et al., Transl Lung Cancer Res; 2024; 13 (1), 5-15. PMID: 38405004

IL-6 is a pleiotropic cytokine that is involved both in immune response and in inflammation, hematopoiesis, bone metabolism, and embryonic development (1). IL-6 plays roles in chronic inflammation that are closely related to chronic inflammatory diseases and autoimmune diseases (2).

Paradoxical effects of IL-6 in preventing or promoting cancer development

A recent review highlights the paradoxical effects of IL-6 in preventing or promoting cancer development (3). During exercise, IL-6 is released from working muscle fibers, enabling the communication between muscles and other organs to maintain energy balance and providing anti-inflammatory benefits (4). It has been shown that muscle-derived IL-6 improves insulin sensitivity in glycogen-storing tissues, hereby stimulating the release of anti-inflammatory cytokines in the blood, mobilizing cytotoxic immune cells, and decreasing DNA damage in cancer cells. These effects of IL-6 may help protect against cancer development and progression.

On the other hand, IL-6 is also induces inflammatory effects by activating the transcription of factors across various inflammatory pathways. It is secreted by immune cells at sites of inflammation and within the tumor environment. Continuous IL-6 signaling at sites of inflammation and within the tumor microenvironment leads to chronic low-grade inflammation and activates pathways that support tumor growth (2, 5).

Thus, although IL-6 mostly promotes tumor growth and progression, it can also exhibit dual effects depending on the context, that is particularly related to the tumor environment and stage. It can stimulate an anti-tumor immune response by activating immune cells, supporting immune surveillance and targeting pre-cancerous cells.

Features & Benefits of BIOMEDICA´s human IL-6 ELISA Assay (#BI-IL6)

• High sensitivity – measurable concentrations in serum AND plasma samples
• Reliable- rigorously validated following international quality guidelines
• Simple – ready to use color coded reagents (7 pre-diluted standards, 2 controls)
• Standardized – calibration using WHO standard

 

 

 

Human Interleukin–6 (IL-6) ELISA ASSAY CHARACTERISTICS

• Catalog Number: BI-IL6
• Method: Sandwich ELISA, HRP/TMB, 12×8-well detachable strips
• Sample type: Serum, plasma (EDTA, citrate, heparin), cell culture supernatatants, urine
• Sample volume: 100 µl / well
• Assay time: 2 h / / 1 h / 1 h / 30 min
• Sensitivity: LOD 0.28 pg/ml; LLOQ: 0.78 pg/ml (measurable concentrations in serum AND plasma samples)
• Standard range: 0 – 200 pg/ml (0 /3.12 / 6.25 / 12.5 / 25 / 25 / 50 /100 /200 pg/ml)  
• Precision: In-between-run (n=3): ≤ 6 % CV, within-run (n=3): ≤ 7 % CV
• Specificity: The human IL-6 ELISA recognizes recombinant and endogenous (natural human IL-6)
• Validation data: precision, accuracy, dilution linearity, parallelism, values for healthy donors are shown here
• Use: research use only

 

Click here for more information on the human IL-6 ELISA

 

Literature

1. Historical overview of the interleukin-6 family cytokine. Kang S, Narazaki M, Metwally H, Kishimoto T J Exp Med. 2020 May 4;217(5):e20190347. doi: 10.1084/jem.20190347. Erratum in: J Exp Med. 2020 May 4;217(5):jem.2019034704212020c. doi: 10.1084/jem.2019034704212020c. PMID: 32267936; PMCID: PMC7201933.
2. IL-6 in inflammation, autoimmunity and cancer. Hirano T. Int Immunol. 2021 Mar 1;33(3):127-148. doi: 10.1093/intimm/dxaa078. PMID: 33337480; PMCID: PMC7799025.
3. The exercise IL-6 enigma in cancer. Orange ST, Leslie J, Ross M, Mann DA, Wackerhage H.Trends Endocrinol Metab. 2023 Nov;34(11):749-763. doi: 10.1016/j.tem.2023.08.001. Epub 2023 Aug 24. PMID: 37633799.
4. IL-6 signaling in acute exercise and chronic training: Potential consequences for health and athletic performance. Nash D, Hughes MG, Butcher L, Aicheler R, Smith P, Cullen T, Webb R. Scand J Med Sci Sports. 2023 Jan;33(1):4-19. doi: 10.1111/sms.14241. Epub 2022 Oct 8. PMID: 36168944; PMCID: PMC10092579.
5. Interleukin-6 in Hepatocellular Carcinoma: A Dualistic Point of View. Nenu I, Toadere TM, Topor I, Țichindeleanu A, Bondor DA, Trella ȘE, Sparchez Z, Filip GA. Biomedicines. 2023 Sep 24;11(10):2623. doi: 10.3390/biomedicines11102623. PMID: 37892997; PMCID: PMC10603956.

July is acknowledged as Bone Cancer and Sarcoma Awareness Month, focusing on increasing awareness about rare and challenging cancers affecting children and adolescents. Sarcoma is a type of cancer that originates in the bones and soft tissues. Soft tissues include muscle, fat, blood vessels, fibrous tissues such as tendons and ligament. More than 70 different subtypes of sarcomas have been reported. However, all sarcomas can be divided into two main groups: soft tissue sarcomas and bone cancers.

Soft Tissue Sarcomas is a rare type of cancer that originates from the growth of cells within the body´s soft tissue. More than 50 different soft tissue sarcomas have been reported (3 ) Soft tissue sarcoma can occur anywhere in the body, but it most frequently develops in arms, legs, and abdomen (4).

Osteosarcoma is the most prevalent type of bone cancer in children and adolescents with and incidence of around 4.4. cases per million children reported each year (1). Genomic alterations, particularly the inactivation of TP53 and RB, are present in most cases of osteosarcoma.

Ewing sarcoma is the second most common bone tumor occurring most frequently in teenagers, with a median age of 15 years. Ewing sarcomas is an aggressive tumor that develops usually in bone, but sometimes in soft tissue, most commonly affecting the lower extremity and pelvis. At diagnosis, up to 25% of patients , commonly found in the lung, bones, and bone marrow (2). This condition is biologically driven by a chromosomal translocation, typically involving the EWS and FLI1 genes.

July is Sarcoma and Bone Cancer Awareness Month

• 5 Things to Know About Bone Cancer and Sarcoma Awareness Month- link

 

Wnt Signalling molecules Sclerostin (SOST) and Dickkopf-1 (DKK-1) in Sarcoma

 

SCLEROSTIN has been shown to be expressed in bone and cartilage forming skeletal tumors. Sclerostin is widely localized to areas in osteoblastic differentiation and ossification (5). In a study using an osteosarcoma mouse model, the administration of sclerostin resulted in inhibited tumor growth and extended survival periods (6).

DKK-1 is a wnt inhibitor that has been shown to partially improve osteosarcoma survival by upregulating aldehyde-dehydrogenase-1A1, neutralizing reactive oxygen species originating from nutritional stress and chemotherapeutic challenge (7). In a mouse model researches demonstrated the use of a DKK-1 targeting vivo morpholino that reduces tumour progression (7).

FGF23 in uterine sarcoma

Human FGF23 has been shown to be highly expressed in uterine sarcoma highlighting its potential as a biomarker for the diagnosis and prognosis of the disease (8).

Sclerostin, DKK-1 and FGF23 can easily be measured in blood, urine and cell culture supernatants with an ELISA assay.

– Sclerostin ELISA (cat. no. BI-20492)

– DKK-1 ELISA (cat. no. BI-20413)

– FGF23 ELISAs (cat. no. BI-20700, BI-20702)

Literature

1. Osteosarcoma. Pediatr Blood Cancer. Eaton BR, Schwarz R, Vatner R, Yeh B, Claude L, Indelicato DJ, Laack N. 2021 May;68 Suppl 2:e28352. doi: 10.1002/pbc.28352. Epub 2020 Aug 11. PMID: 32779875.
2. Ewing sarcoma. Pediatr Blood Cancer. Eaton BR, Claude L, Indelicato DJ, Vatner R, Yeh B, Schwarz R, Laack N. 2021 May;68 Suppl 2:e28355. doi: 10.1002/pbc.28355. PMID: 33818887.
3. More Than 50 Subtypes of Soft Tissue Sarcoma: Paving the Path for Histology-Driven Treatments. Katz D, Palmerini E, Pollack SM. Am Soc Clin Oncol Educ Book. 2018 May 23;38:925-938. doi: 10.1200/EDBK_205423. PMID: 30231352.
4. Malignant Soft-Tissue Sarcomas. Hematol Oncol Clin North Am. Brownstein JM, DeLaney TF. 2020 Feb;34(1):161-175. doi: 10.1016/j.hoc.2019.08.022. Epub 2019 Oct 28. PMID: 31739942.
5. Sclerostin expression in skeletal sarcomas. Shen J, Meyers CA, Shrestha S, Singh A, LaChaud G, Nguyen V, Asatrian G, Federman N, Bernthal N, Eilber FC, Dry SM, Ting K, Soo C, James AW. Hum Pathol. 2016 Dec;58:24-34. doi: 10.1016/j.humpath.2016.07.016. Epub 2016 Aug 3. PMID: 27498059; PMCID: PMC6560186.
6. Antitumor Effect of Sclerostin against Osteosarcoma. Ideta H, Yoshida K, Okamoto M, Sasaki J, Kito M, Aoki K, Yoshimura Y, Suzuki S, Tanaka A, Takazawa A, Haniu H, Uemura T, Takizawa T, Sobajima A, Kamanaka T, Takahashi J, Kato H, Saito N. Cancers (Basel). 2021 Nov 29;13(23):6015. doi: 10.3390/cancers13236015. PMID: 34885123; PMCID: PMC8656567.
7. Morpholino-driven blockade of Dkk-1 in osteosarcoma inhibits bone damage and tumour expansion by multiple mechanisms. Pan S, Cesarek M, Godoy C, Co CM, Schindler C, Padilla K, Haskell A, Barreda H, Story C, Poole R, Dabney A, Gregory CA. Br J Cancer. 2022 Jul;127(1):43-55. doi: 10.1038/s41416-022-01764-z. Epub 2022 Mar 11. PMID: 35277659; PMCID: PMC9276700.
8. Fibroblast Growth Factor 23 is a Potential Prognostic Biomarker in Uterine Sarcoma. Yang L, Cai Y, Wang Y, Huang Y, Zhang C, Ma H, Zhou JG. Technol Cancer Res Treat. 2024 Jan-Dec;23:15330338241245924. doi: 10.1177/15330338241245924. PMID: 38613349; PMCID: PMC11015760.

We´re excited to offer our customers a significant price drop by 15% on our

human Interleukin-6 ELISA kit  (cat. no. BI-IL6)

Quality and fully validated assay with ready to use reagents for affordable and efficient research!

⇒ Contact us or our local representative

Making IL-6 ELISA Kits More Affordable

Take 15% OFF of the human IL-6 ELISA Assay now through end of 2024!

BIOMEDICA´s human Interleukin-6 (IL-6) ELISA Assay is highly sensitive and shows detectable values in serum and in plasma samples.

Features & Benefits

• High Specificity – using characterized epitope-mapped antibodies
• High Sensitivity – detectable values in both serum and plasma 
• Superior Quality – validated according to international quality guidelines
• Standardized – use of WHO intern.standards for kit calibration & harmonization 
• User-Friendly –ready to use color coded prediluted standards & controls

 

BIOMEDICA Human IL-6 ELISA kit 

• Product code: BI-IL6
• Method: ELISA
• Time to result: 4.5 hours
• Sample types: human serum, plasma (EDTA, citrate, heparin), cell culture supernatants, urine
• Sample volume: 100 µl/well
• Sensitivity LOD: 0.28 pg/ml  (measurable concentrations in serum AND plasma samples!)
• Standard curve range: 0 – 200 pg/ml (0 / 3.12 / 6.25 / 12.5 / 25/ 50 / 100 / 200)
• Specificity: Endogenous and recombinant human IL-6
• Protokol booklet
• Validation data file

 

About Interleukin-6

Interleukin-6 (IL-6) is a multifunctional cytokine that plays an important role in the body´s response to tissue injury or infection. Il-6 is produced by various cells, including T-cells, B-cells, macrophages, as well as vascular endothelial cells, mast cells, and dentritic cells (1). Il-6 secretion is stimulated during inflammatory response and travels through the bloodstream to the liver, where it induces the production of acute phase reactants such as C-reactive protein and others (1).

Clinical significance of Interleukin-6

-Inflammatory diseases: elevated IL-6 levels are detected in various inflammatory conditions such as rheumatoid arthritis (2), systemic lupus erythematosus (3) , and inflammatory bowel disease (4). Therapies targeting Il-6 have been already approved (5).

-Cancer: Il-6 is abundantly present in the tumor microenvironment of various tumours. It promotes tumnorigenesis, invasiveness, and metastases in cancer (6). New perspectives in cancer immunotherapy targeting IL-6 are discussed (7).

-Metabolic diseases: Dysregulated IL-6 activity is associated with pathologies involving chronic inflammation and autoimmunity including metabolic diseases like obesity, metabolic syndrome or type-2 diabetes (8).

 Literature

1. Interleukin 6: at the interface of human health and disease. Grebenciucova E et al., Front Immunol. 2023; 28;14:1255533. PMID: 37841263.
2. Interleukin-6 in Rheumatoid Arthritis. Pandolfi F et al., Int J Mol Sci. 2020 ;  23;21(15):5238. PMID: 32718086; PMCID:.
3. Role of IL-6 and IL-6 targeted therapy in systemic lupus erythematosus. Nepal D, Gazeley D. Rheumatology (Oxford). 2023; 1;62(12):3804-3810. PMID: 37594751.
4. Cytokines of the interleukin-6 family as emerging targets in inflammatory bowel disease. Garbers C, Lokau J. Expert Opin Ther Targets. 2024; 28(1-2):57-65. PMID: 38217849.
5. Therapeutic uses of anti-interleukin-6 receptor antibody. Kang S et al., Int Immunol. 2015; 27(1):21-9. PMID: 25142313.
6. The Role of IL-6 in Cancer Cell Invasiveness and Metastasis-Overview and Therapeutic Opportunities. Rašková M et al., Cells. 2022; 21;11(22):3698. PMID: 36429126.
7. New perspectives in cancer immunotherapy: targeting IL-6 cytokine family. Soler MF et al., J Immunother Cancer. 2023; 11(11):e007530. PMID: 37945321.
8. IL-6 family cytokines as potential therapeutic strategies to treat metabolic diseases. Zhao J et al., Cytokine. 2021; 144:155549. PMID: 33962843

Fibroblast growth factor 23 (FGF23) is a hormone primarily known for its role in mineral metabolism, particularly in regulating phosphate homeostasis.

FGF23 is primarily produced in the bone by osteocytes and acts on the kidneys to regulate phosphate reabsorption and vitamin D metabolism. FGF23 helps to maintain phosphate levels within the normal range by promoting urinary phosphate excretion and inhibiting the production of vitamin D (1). The dysregulation of FGF23 can lead to conditions such as hypophosphatemic rickets and hyperphosphatemia.

FGF23 and its effects on the heart

Numerous clinical studies have shown that elevated plasma level concentrations of FGF23 are linked to left ventricular hypertrophy (LVH), heart failure, and increased mortality in the general population, particularly among individuals with chronic kidney disease (CKD) (2). The exact mechanisms by which FGF23 affects the heart are still under investigation, but several possible pathways have been suggested. For instance, FGF23 may induce hypertrophy directly through binding to specific FGF23 receptors expressed by cardiomyocytes in the heart. FGF23 may also promote hypertrophy indirectly by altering mineral metabolism, leading to increased circulating levels of phosphorus, which can contribute to cardiovascular damage.

In addition, FGF23 may have effects on the endothelium, the inner lining of blood vessels. It has been suggested that FGF23 may hinder endothelial function and promote vascular calcification, thereby contributing to the development of cardiovascular disease. Further research is needed to fully understand the exact mechanisms through which FGF23 affects the heart and its role in cardiovascular disease (3).

Measurement of FGF23

FGF23 concentrations can be measured with blood tests. The most common way for measuring FGF23 is with a conventional ELISA assay (enzyme-linked immunosorbent assay). The ELISA utilizes specific antibodies that recognize and bind FGF23 molecules present in the sample. The intensity of the antibody-antigen reaction is measured, allowing an easy quantification of FGF23 in the respective sample.

Currently there are two different assays that allow the measurement of FGF23 in blood samples:

Intact FGF23 Assays

intact FGF23 represents the full length, biologically active form of the hormone. It consists of the complete FGF23 protein structure without being enzymatically cleaved.

 

The BIOMEDICA FGF23 (intact) human ELISA (cat. no. BI-20700)

is a sandwich-based immunoassay with an anti-human FGF23 capture antibody recognizing a structural epitope in the N-terminal part of FGF23 and a detection antibody binding to the C-terminal part of mature FGF23.

 

FGF23 C-terminal Assays
The c-terminal fragments of FGF23 are the result of the enzymatic cleavage of the intact FGF23 molecule.
Of note: all commercially available FGF23 c-terminal assays detect both c-terminal FGF23 fragments as well as the intact FGF23 molecule!

 

The BIOMEDICA FGF23 (C-terminal) human multi-matrix ELISA (cat. no. BI-20702)

is a sandwich-based immunoassayw hich recognizes multiple epitopes in the C-terminal part of FGF23.

 

Features & Benefits

• Validated ELISA kits following international quality guidelines
• Biomedica´s FGF23 assay have been used in numerous studies 

 

validation reports and citations can be downloaded here

Literature

1. Biology of Fibroblast Growth Factor 23: From Physiology to Pathology. Courbebaisse M, Lanske B. Cold Spring Harb Perspect Med. 2018 May 1;8(5):a031260. doi: 10.1101/cshperspect.a031260. PMID: 28778965; PMCID: PMC5932574.
2. Direct and indirect effects of fibroblast growth factor 23 on the heart. Nakano T, Kishimoto H, Tokumoto M Front Endocrinol (Lausanne). 2023 Feb 24;14:1059179. doi: 10.3389/fendo.2023.1059179. PMID: 36909314; PMCID: PMC9999118.
3. FGF23 directly impairs endothelium-dependent vasorelaxation by increasing superoxide levels and reducing nitric oxide bioavailability. Silswal N, Touchberry CD, Daniel DR, McCarthy DL, Zhang S, Andresen J, Stubbs JR, Wacker MJ. Am J Physiol Endocrinol Metab. 2014 Sep 1;307(5):E426-36. doi: 10.1152/ajpendo.00264.2014. Epub 2014 Jul 22. PMID: 25053401; PMCID: PMC4154070.

 

for  ELISA and Luminex Assays and microRNA Analysis

Biomedica Immunoassays is dedicated to developing and producing high-quality ELISA assay kits.

Building on this foundation, we also specialize in providing customized sample testing services for customers in academia, biotechnology, and the pharmaceutical industries.

Sample Testing Services 

for  ELISA and Luminex Assays and microRNA Analysis

Share the details of your project with us! At Biomedica, our scientists will consult with you to discuss your project and provide scientific and/or technical support for your ongoing research, ensuring reliable and relevant results. We will supply you with raw data as well as a professionally formatted analytical report.

We offer:

• Customized Services – Flexibility to meet your project needs
• Expertise – Trained and experienced laboratory staff
• Quality Assurance – High-quality equipment adhering to strict quality guidelines
• Timeliness – Rapid turn-around times to meet your deadlines
• Reliability – Verified results with comprehensive analytical reports

 

Sample Testing Services for ELISA and Luminex Assays and microRNA Analysis

We will measure your clinical or pre-clinical samples for any selected biomarker using ELISA (enzyme-linked immunosorbent assay) or Luminex.

• Clinical Samples: serum, plasma, urine, cell culture supernatants
• Pre-Clinical Samples: mouse, rat, rabbit, or other species (e.g., NT-proBNP or NT-proANP measurement)
• Custom Applications: contact us for tailored solutions

 

Click here to learn about the workflow. Our measurement services include:

ELISA Assay Kits

We offer services for our proprietary Biomedica assays (see product list) as well as ELISA Assay Kits from other providers, covering a wide range of biomarker analytes.

Luminex Technology Multiplex Assays

We utilize Luminex xMAP® (multiple analyte profiling) technology-based immunoassays to measure your samples, enabling the simultaneous detection and quantification of multiple biomarkers.

For additional details, please refer to our workflow chart or reach out to us directly to discuss how we can support your specific research project

NEXT-GENERATION SEQUENCING & RT-qPCR MICRORNA SERVICES

We provide a comprehensive range of high-quality RNA services, including RNA extraction, next-generation sequencing (NGS), RT-qPCR, and custom analysis of microRNA signatures, all performed by our experienced laboratory staff. Our services include:

• RNA extraction from biofluids (serum, plasma, extracellular vesicles), cells, and tissues (quality control of total RNA utilizes Bioanalyzer chips).
• Next-generation sequencing (NGS).
• RT-qPCR.
• Cell-type specific microRNA/mRNA analysis in complex tissues, along with custom analysis of microRNA signatures.

 

For more details about our microRNA services, please visit our website or contact us directly.

 

Further reading

Enzyme-Linked Immunosorbent Assay: Types and Applications. Hayrapetyan H et al., Methods Mol Biol. 2023;2612:1-17. doi: 10.1007/978-1-0716-2903-1_1. PMID: 36795355.

A comprehensive review of Dynamic Chemical Labelling on Luminex xMAP technology: a journey towards Drug-Induced Liver Injury testing. Marín-Romero A, Pernagallo S Anal Methods. 2023 Nov 23;15(45):6139-6149. doi: 10.1039/d3ay01481a. PMID: 37965948.

Circulating microRNAs as novel biomarkers for bone diseases – Complex signatures for multifactorial diseases? Hackl M et al., Mol Cell Endocrinol. 2016 Sep 5;432:83-95. doi: 10.1016/j.mce.2015.10.015. Epub 2015 Oct 23. PMID: 26525415.

For affordable and efficient research

Interleukin-6 (IL-6) is a multifunctional cytokine that plays an important role in the body´s response to tissue injury or infection. Il-6 is produced by various cells, including T-cells, B-cells, macrophages, as well as vascular endothelial cells, mast cells, and dentritic cells (1). Il-6 secretion is stimulated during inflammatory response and travels through the bloodstream to the liver, where it induces the production of acute phase reactants such as C-reactive protein and others (1).

Human Interleukin-6 ELISA Assay Kit – high sensitivity

BIOMEDICA´s human Interleukin-6 (IL-6) ELISA Assay is highly sensitive and shows detectable values in serum and in plasma samples.

Features & Benefits

• High Specificity – using characterized epitope-mapped antibodies
• High Sensitivity – measurable values in both serum and plasma 
• Superior Quality – validated according to international quality guidelines
• Standardized – use of WHO intern.standards for kit calibration & harmonization 
• User-Friendly – ready to use color coded prediluted standards & controls

 

Take 15% off the human IL-6 ELISA Assay now through end of 2024!

Use Promotion Code: BCIL62024 on your order.

 

Human IL-6 ELISA Kit (cat. no. BI-IL6)       

• Method: Sandwich ELISA, HRP/TMB, 12×8-well detachable strips
• Sensitivity LOD: 0.28 pg/ml  (measurable concentrations in serum AND plasma samples!)
• Sample types: human serum, plasma (EDTA, citrate, heparin), cell culture supernatants, urine)
• Sample volume: 100 µl/well
• Dynamic range: 0 – 200 pg/ml (0 / 3.12 / 6.25 / 12.5 / 25/ 50 / 100 / 200)
• Time to result: 4.5 hours
• Specificity: Endogenous and recombinant human IL-6
• Protokol booklet
• Validation data file
• Alternative name: Interleukin-6

 

 

Clinical significance of Interleukin-6

• Inflammatory diseases: elevated IL-6 levels are detected in various inflammatory conditions such as rheumatoid arthritis (2), systemic lupus erythematosus (3) , and inflammatory bowel disease (4). Therapies targeting Il-6 have been already approved (5).

 

• Cancer: Il-6 is abundantly present in the tumor microenvironment of various tumours. It promotes tumnorigenesis, invasiveness, and metastases in cancer (6). New perspectives in cancer immunotherapy targeting IL-6 are discussed (7).

 

• Metabolic diseases: Dysregulated IL-6 activity is associated with pathologies involving chronic inflammation and autoimmunity including metabolic diseases like obesity, metabolic syndrome or type-2 diabetes (8).

 

RELATED BIOMEDICA KITS

Human VEGF ELISA (BI-VEGF), Human Angiopoietin-2 ELISA (BI-ANG2)

 

LITERATURE

1. Interleukin 6: at the interface of human health and disease. Grebenciucova E, VanHaerents S. Front Immunol. 2023 Sep 28;14:1255533. doi: 10.3389/fimmu.2023.1255533. PMID: 37841263; PMCID: PMC10569068.
2. Interleukin-6 in Rheumatoid Arthritis. Pandolfi F, Franza L, Carusi V, Altamura S, Andriollo G, Nucera E. Int J Mol Sci. 2020 Jul 23;21(15):5238. doi: 10.3390/ijms21155238. PMID: 32718086; PMCID: PMC7432115.
3. Role of IL-6 and IL-6 targeted therapy in systemic lupus erythematosus. Nepal D, Gazeley D. Rheumatology (Oxford). 2023 Dec 1;62(12):3804-3810. doi: 10.1093/rheumatology/kead416. PMID: 37594751.
4. Cytokines of the interleukin-6 family as emerging targets in inflammatory bowel disease. Garbers C, Lokau J. Expert Opin Ther Targets. 2024 Jan-Feb;28(1-2):57-65. doi: 10.1080/14728222.2024.2306341. Epub 2024 Jan 23. PMID: 38217849.
5. Therapeutic uses of anti-interleukin-6 receptor antibody. Kang S, Tanaka T, Kishimoto T. Int Immunol. 2015 Jan;27(1):21-9. doi: 10.1093/intimm/dxu081. Epub 2014 Aug 20. PMID: 25142313.
6. The Role of IL-6 in Cancer Cell Invasiveness and Metastasis-Overview and Therapeutic Opportunities. Rašková M, Lacina L, Kejík Z, Venhauerová A, Skaličková M, Kolář M, Jakubek M, Rosel D, Smetana K Jr, Brábek J. Cells. 2022 Nov 21;11(22):3698. doi: 10.3390/cells11223698. PMID: 36429126; PMCID: PMC9688109.
7. New perspectives in cancer immunotherapy: targeting IL-6 cytokine family. Soler MF, Abaurrea A, Azcoaga P, Araujo AM, Caffarel MM.J Immunother Cancer. 2023 Nov;11(11):e007530. doi: 10.1136/jitc-2023-007530. PMID: 37945321; PMCID: PMC10649711.
8. IL-6 family cytokines as potential therapeutic strategies to treat metabolic diseases. Zhao J, Turpin-Nolan S, Febbraio MA. Cytokine. 2021 Aug;144:155549. doi: 10.1016/j.cyto.2021.155549. Epub 2021 May 4. PMID: 33962843.

We are excited to be soon exhibiting at the International Conference on Children’s Bone Health (ICCBH) in Salzburg, Austria from June 22-25, 2024.

Join us at booth number 4 and explore our widely trusted Biomarker ELISA Assay Kits including Fibroblast Growth Factor (FGF23), Sclerostin, Periostin, NT-proCNP, and many others.

We look forward to connecting with you!

Join us at the International Conference on Children’s Bone Health

Click here for more information about the conference for anyone who is interested in 

bone metabolism and bone mass in children, adolescents and young adults.

The ICCBH conference aims to unite researchers, clinicians, health professionals, and others from different fields to gain an understanding of the developing skeleton with regards to childhood health and disease. Latest advancements, innovative therapies, and genetic discoveries will be discussed.

More about Biomarkers in Bone Biology  

Bone cells release biomarkers during bone remodeling. They can be used in assessing bone diseases and represent useful therapeutic targets. Bone biomarkers can easily be detected in serum and plasma samples by immunoassay.  

A recent review by Ponds-Belda OD et al., Mineral Metabolism in Children: Interrelation between Vitamin D and FGF23 focuses on various aspects of FGF23 metabolism in children, reference values,  and other key variables involved in mineral homeostasis. 

BIOMEDICA offers quality kits to measure various bone biomarkers 

Sclerostin ELISA (SOST; cat.no. BI-20492)  

OPG ELISA (Osteoprotegerin; cat.no. BI-20403)  

RANKL ELISA (soluble RANKL; cat.no. BI-20462)  

DKK-1 ELISA (Dickkopf-1; cat.no. BI-20413)  

FGF23 intact ELISA (Fibroblast growth factor-23 intact; cat.no. BI-20700) 

FGF23 C-terminal ELISA (Fibroblast growth factor-23 C-terminal; cat.no. cat.no. BI-20702) 

PERIOSTIN ELISA (POSTN, BI-20433) 

NT-proCNP ELISA (NT-C-type natriuretic peptide, BI-20812)

 TRUSTED – cited in over 1300 publications

• Kit validations follows international quality guidelines
• Developed & manufactured by Biomedica in Austria