When using an ELISA assay, it is important to ensure that the results are specific, accurate, sensitive, and reproducible. The ELISA assay reliability varies among kit suppliers, so choosing the “right” ELISA requires careful consideration. Access to the assay´s validation data before making a choice may be helpful.
ELISA Assay Reliability
At BIOMEDICA we take pride in developing and manufacturing our ELISA kits following a stringent manufacturing and quality control process, that enables us to maintain consistent and reproducible outcomes with every lot we produce.
At Biomedica we develop and manufacture our ELISA assays with care
All BIOMEDICA kits are fully validated and come with sample data for healthy human subjects, ready-to-use standards and controls. We supply our kits with color-coded vials, and some of the reagents are “colorful” as well, to make the kits easy to use and to avoid possible pipetting errors, To increase transparency, we publish the validation data of every ELISA assay kit on our website.
BIOMEDICA´s QUALITY GUIDELINES
AT BIOMEDICA, our goal is to supply reliable and well-validated ELISA kits for your research.
Here is how we ensure product excellence:
- Optimization: we diligently optimize all Biomedica assay to guarantee reliability, sensitivity, and precision.
- Validation: our kits undergo an extensive validation process in accordance with international quality guidelines (FDA, EMA, and ICH), ensuring the kits accuracy and efficiency.
- Expert Team: our dedicated team consists of highly qualified scientists, many with doctorate-level education and industry training. Our team has extensive research experience and contributes to the development, production, and customer service aspects of our products.
- Quality Management: Biomedica adheres to the ISO 9001: 2015 certified quality management system in our manufacturing process, ensuring consistent and high-quality products.
With these measures in place, we are committed to deliver ELISA assays that meet the highest standards of performance and reliability.
Learn more: https://www.bmgrp.com/quality
Related literature
Interference in ELISA. Matson RS. 2023. Methods Mol Biol. 2612:91-99. doi: 10.1007/978-1-0716-2903-1_7. PMID: 36795361.
Abstract
ELISA is a well-established technique used worldwide to quantify analytes present in a diverse milieu of biological samplings. It is especially important to clinicians who rely on the accuracy and precision of the test to administer patient care. Those results are to be held with great scrutiny since the assay is subject to error caused by interfering substances found in the sample matrix. In this chapter, we examine the nature of such interferences and discuss approaches to identify and offer remedies to remove the interference and validate the assay.
Validation of an enzyme-linked immunosorbent assay (ELISA) for quantification of endostatin levels in mice as a biomarker of developing glomerulonephritis. Wallwitz J, Aigner P, Gadermaier E, Bauer E, Casanova E, Bauer A, Stoiber D. 2019. PLoS One. 14(8):e0220935. doi: 10.1371/journal.pone.0220935. PMID: 31404120; PMCID: PMC6690585.
Abstract
Endostatin, the C-terminal fragment of type XVIII collagen, was shown to be one of the most potent endothelial cell-specific inhibitors of angiogenesis. As altered circulating endostatin concentration is associated with impaired kidney function, new tools for measuring endostatin in rodents may be helpful to further investigate and understand its role within kidney disease progression. A novel and commercially available ELISA for the quantification of mouse and rat endostatin was developed and validated according to international quality guidelines including the parameters specificity, robustness, accuracy, dilution linearity, precision, limit of detection (LOD) and lower limit of quantification (LLOQ). Endostatin and blood urea nitrogen (BUN) concentration were measured in mice with a glomerulonephritis phenotype. The validation revealed that within the range of 0.5-32 nmol/L the immunoassay is robust and highly specific for the measurement of rodent endostatin with high sensitivity (LOD 0.24 nmol/L, LLOQ 0.5 nmol/L) and good reproducibility (intra- and inter-assay CV <10%). Also accuracy and dilution linearity were within the range of acceptance. BCL2 transgenic and ETV6/RUNX1;BCL2 double transgenic mice develop a glomerulonephritis phenotype over time, which was displayed by staining of kidney sections. Even before full manifestation of disease serum endostatin concentration rises significantly, whereas BUN levels just slightly increase. This newly developed and commercially available ELISA provides a reliable and accurate tool for the quantification of mouse and rat endostatin and may give new perspectives in the investigation of the role of endostatin as an important and early biomarker for reduced kidney function. Measurement of endostatin concentration is recommended to be used as a superior biomarker for chronic kidney disease compared to BUN.
Practical Guide to Immunoassay Method Validation. Andreasson U et al. 2015. Front Neurol. 19;6:179. doi: 10.3389/fneur.2015.00179. PMID: 26347708; PMCID: PMC4541289.
EZ4U – Easy and Reliable Assay for Cell Viability Analysis
Cell viability quantifies the percentage of living and healthy cells within a given cell population. Cell viability analysis assays are employed to assess cell survival for instance after treatment with substances during drug screening.
Testing of Cell Viability with Biomedica´s EZ4U Assay
The EZ4U assay is a metabolic assay (like the MTT assay) that quantifies cell health by measuring the reduction of the colorimetric substrate through the activity of mitochondrial enzymes.
Cell viability assays are widely used in cell biology research. The EZ4U test kit is a reliable and straightforward non-radioactive assay that can be completed within two to five hours, depending on the cell type studied. The EZ4U assay employs non-toxic tetrazolium salts, which are 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. Furthermore, as the assay procedure is identical to thymidine incorporation procedure, no changes in test protocols are necessary. 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. For examples please follow the citations by clicking this link.
EZ4U Cell Proliferation and Cytotoxicity Assay –straightforward with a single incubation step using living cells
The EZ4U assay (Biomedica, Austria) was used in a recent study investigating the effects of RNA methylation, namely m6A methylation, on the renal cell carcinoma (ACHN and 769P) cell lines. Renal cell carcinoma (RCC) accounts for about 2% of cancer-related deaths. Patients with metastatic RCC have a poor prognosis with an approximate 5% survival rate. Despite therapeutical advancements, including checkpoint immunotherapy, the improvement in patient survival rates has been rather moderate.
Learn more: 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, Klümper N, Schmidt D, Ritter M, Ellinger J, Hauser S. Am J Transl Res. 2023 Mar 15;15(3):1744-1755. PMID: 37056835; PMCID: PMC10086911.
Abstract
Background: N6-methyladenosine (m6A) is one of the most common RNA modifications in eukaryotes and has effects on RNA structure and stability. Recent studies have shown that m6A methylation is involved in human carcinogenesis. In the present study, we investigated the effects of m6A demethylases FTO and ALKBH5 on renal cell carcinoma (RCC) cell lines. Methods: The epithelial-mesenchymal in vitro knockdowns of FTO and ALKBH5 induced by antisense oligonucleotides (LNA-GapmeR system) were established in RCC cell lines. Their effects on migration and proliferation were investigated subsequently. The influence of FTO and ALKBH5 knockdown on key epithelial-mesenchymal transition (EMT) genes was analyzed. Results: Inactivation of FTO and ALKBH5 resulted in decreased proliferation and motility in all cell lines examined (ACHN, Caki-1, 769-P). Vimentin (VIM) was downregulated after the knockdown of FTO and ALKBH5, indicating an EMT switch. Conclusions: Knockdown of the m6A erasers FTO and ALKBH5 inhibits the malignant potential in the cell cultures studied by means of an EMT switch.
EZ4U Cell Proliferation & Cytotoxicity Assay (cat.no. BI-5000)
- Non-radioactive & non-toxic assay
- Reliable & Sensitive
- Convenient single-step incubation – for use on living cells
- Widely cited in more than 240 publications
Find out more: BROCHURE – EZ4U cell proliferation and cytotoxicity assay
At Biomedica we develop and manufacture quality ELISAs to quantify cytokine release
Our ELISAs to quantify cytokine release are validated according to international quality guidelines to ensure their consistency, specificity, precision, and robustness. The validation data files can be found on the respective product pages www.bmgrp.com.
Our kits are designed to specifically quantify cytokine release in various biological matrices (e.g. serum, plasma, cell culture).
WHO reference reagents for a harmonized standardization
All our cytokine kits are standardized using WHO reference reagents/standards to allow cross-comparison of results when using different reagent sets during a study (1).
BIOMEDICAs CYTOKINE ELISA KITS
IL-6 ELISA (cat. no. BI-IL6)
The Biomedica IL-6 (interleukin-6) ELISA kit is a sandwich ELISA that incorporates two epitope-mapped antibodies that specifically bind to human IL-6 in the respective samples.
Capture antibody (pre-coated on a 96-well microtiter plate): recombinant IL-6 antibody (specific for human IL-6).
Detection antibody: polyclonal IL-6 antibody (streptavidin-HRPO labeled), specific for human IL-6.
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- Method: sandwich ELISA
- Sample type: serum, plasma, cell-culture, urine
- Sample volume: 100µl / well
- Assay time: 4.5 hrs
- Standard range: 0 / 3.1 – 200 pg/ml
- Sensitivity: LOD: 0.28 pg/ml; LLOQ: 0.78 pg/ml (measurable concentrations in serum AND plasma samples!)
- Precision: in-between-run (n=9 ): ≤ 6 % CV, within-run (n=3): ≤ 7 % CV
- Specificity: the ELISA recognizes recombinant and endogenous (natural) human IL-6
- Standard matrix: serum based matrix containing recombinant IL-6 including 8x vials of pre-diluted standards, lyophilized
- Controls: 2 controls (high and low) included
VEGF ELISA (cat. no. BI-VEGF)
The Biomedica VEGF (Vascular Endothelial Growth Factor) ELISA kit is a sandwich ELISA that incorporates two epitope-mapped antibodies that specifically bind to human VEGF in the respective samples.
Capture antibody (pre-coated on a 96-well microtiter plate): recombinant VEGF antibody (specific for human VEGF) recognizes a structural epitope in the conserved receptor binding- site of the VEGF peptide. The antibody binds to all VEGF isoforms.
Detection antibody: polyclonal VEGF antibody (streptavidin-HRPO labeled), specific for human VEGF, recognizing multiple linear epitopes that are concentrated in the first 120 amino acids in the N-terminal region of the VEGF molecule.
- Method: sandwich ELISA
- Sample type: serum, plasma, cell-culture, urine
- Sample volume: 10µl / well
- Assay time: 4.5 hrs
- Standard range: 0 / 31.2 – 2000 pg/ml
- Sensitivity: LOD: 2.5 pg/ml; LLOQ: 15.6 pg/ml (measurable concentrations in serum AND plasma samples)
- Precision: in-between-run: (n=3): ≤ 6 % CV, Within-run (n=3): ≤ 3 % CV
- Specificity: the ELISA recognizes recombinant and endogenous (natural) human VEGF including all circulating VEGF isoforms including VEGF165b
- Standard matrix: Serum based matrix containing recombinant VEGF, including 8x vials of pre-diluted standards, lyophilized
- Controls: 2 controls (high and low) included
ANGIOPOIETIN-2 ELISA (cat. no. BI-ANG2)
The Biomedica ANG2 (Angiopoietin-2) ELISA kit is a sandwich ELISA that incorporates two epitope-mapped antibodies that specifically bind to human Angiopoietin-2 in the respective samples.
Capture antibody (pre-coated on a 96-well microtiter plate): recombinant ANG2 antibody (specific for human ANG2).The capture antibody has a structural epitope that binds to the receptor binding site of human Angiopoietin-2. The receptor binds to TEL / TIE2 protein.
Detection antibody: polyclonal ANG2 antibody (streptavidin-HRPO labeled), specific for human ANG2, recognizing several linear epitopes that are distributed over the entire Angiopoietin-2 molecule.
- Method: sandwich ELISA
- Sample type: serum, plasma, cell-culture, urine
- Sample volume: 20µl / well
- Assay time: 3.5 hrs
- Standard range: 0 / 12.5 – 400 pg/ml
- Sensitivity: 3.7 pmol/l (= 203 pg/ml)
- Precision: In-between-run (n=9): ≤ 6 % CV, Within-run (n=3): ≤ 8 % CV
- Specificity: the ELISA recognizes recombinant and endogenous (natural) human ANG2. The assay most probably detects all three ANG2 isoforms, as determined by epitope mapping and analysis of the ANG2 sequence. ANG1 is not detected in this ELISA assay.
- Standard matrix: Serum based matrix containing recombinant ANG2, including 8x vials of pre-diluted standards, lyophilized
- Controls: 2 controls (high and low) included
Also available: Mouse /rat Angiopoietin-2 ELISA (cat. no. BI-ANG2MR)
Related publications
1. International reference reagents
2. Targeting IL-6 trans-signalling: past, present and future prospects. Rose-John S, Jenkins BJ, Garbers C, Moll JM, Scheller J. Nat Rev Immunol. 2023 Apr 17:1–16. doi: 10.1038/s41577-023-00856-y. Epub ahead of print. PMID: 37069261; PMCID: PMC10108826.
Abstract
Interleukin-6 (IL-6) is a key immunomodulatory cytokine that affects the pathogenesis of diverse diseases, including autoimmune diseases, chronic inflammatory conditions and cancer. Classical IL-6 signalling involves the binding of IL-6 to the membrane-bound IL-6 receptor α-subunit (hereafter termed ‘mIL-6R’) and glycoprotein 130 (gp130) signal-transducing subunit. By contrast, in IL-6 trans-signalling, complexes of IL-6 and the soluble form of IL-6 receptor (sIL-6R) signal via membrane-bound gp130. A third mode of IL-6 signalling – known as cluster signalling – involves preformed complexes of membrane-bound IL-6-mIL-6R on one cell activating gp130 subunits on target cells. Antibodies and small molecules have been developed that block all three forms of IL-6 signalling, but in the past decade, IL-6 trans-signalling has emerged as the predominant pathway by which IL-6 promotes disease pathogenesis. The first selective inhibitor of IL-6 trans-signalling, sgp130, has shown therapeutic potential in various preclinical models of disease and olamkicept, a sgp130Fc variant, had promising results in phase II clinical studies for inflammatory bowel disease. Technological developments have already led to next-generation sgp130 variants with increased affinity and selectivity towards IL-6 trans-signalling, along with indirect strategies to block IL-6 trans-signalling. Here, we summarize our current understanding of the biological outcomes of IL-6-mediated signalling and the potential for targeting this pathway in the clinic.
Fibroblast growth factor 23 (FGF23) is a hormone that plays a crucial role in regulating serum phosphate and vitamin D levels within the body. FGF23 is primarily produced in the bone by osteocytes and osteoblasts in response to factors such as oral phosphate intake or elevated serum Vitamin D concentrations. The regulation of normal serum phosphorus levels is primarily achieved through a highly controlled process occurring in the kidney where phosphate reabsorption takes place. Patients suffering from chronic kidney disease (CKD) have high plasma FGF23 levels and FGF23 serves as a sensitive biomarker for detecting abnormal renal phosphate handling. Notably, FGF23 levels increase during the early stages of kidney dysfunction, providing valuable insights into the underlying renal impairments (1, 2).
Effects of FGF23 on the heart
High FGF23 concentrations have been found to be associated with multiple cardiac diseases, including left ventricular hypertrophy, heart attacks, heart failure, and cardiovascular related deaths (3-5).
Present findings exploring the relationship of FGF23 and cardiac events are presented in a recent review. The authors further discuss the potential mechanisms by which FGF23 directly or indirectly triggers left ventricular hypertrophy (6).
Learn more: Direct and indirect effects of fibroblast growth factor 23 on the heart. Nakano T et al., 2023.
Download our leaflet “FGF23 – an overview” here
How can FGF23 be measured?
Circulating FGF23 concentrations can be measured through blood tests by immunoassays. A widely used method for measuring FGF23 is with an ELISA assay (enzyme-linked immunosorbent assays). FGF23 ELISA assays utilize specific antibodies that recognize and bind FGF23 present in the sample.
Currently, there are two different assays commercially available for measuring circulating FGF23 in blood samples (7).
Intact FGF23 Assays
intact FGF23 (iFGF23) represents the full length, biologically active form of the hormone. It consists of the complete FGF23 protein structure without being enzymatically cleaved. The two antibodies in these assays target the N-terminal part and the C-terminal domain of the FGF23 molecule, respectively.
FGF23 C-terminal Assays
The c-terminal fragments of FGF23 (cFGF23) are the result of the enzymatic cleavage of the intact FGF23 molecule. The antibodies utilized in the cFGF23 assays bind to specific epitopes that are located in the c-terminal domain of the FGF23 molecule.
Noteworthy, all commercially available FGF23 c-terminal assays detect both c-terminal FGF23 fragments as well as the intact FGF23 molecule (7).
BIOMEDICA has developed two distinct ELISA assays to reliably quantify FGF23 concentrations in human serum and plasma.
· FGF23 intact ELISA (cat. no. BI-20700)
· FGF23 (C-terminal) ELISA (cat. no. BI-20702)
- Validated FGF23 ELISA kits according to international quality guidelines
- Numerous references in top-ranking journals
All Assays are Developed & Manufactured by Biomedica
Literature
- The regulation of FGF23 under physiological and pathophysiological conditions. Rausch S, Föller M. Pflugers Arch. 2022 Mar;474(3):281-292. doi: 10.1007/s00424-022-02668-w. Epub 2022 Jan 27. PMID: 35084563; PMCID: PMC8837506.
- Regulation and Effects of FGF23 in Chronic Kidney Disease. Musgrove J, Wolf M. Annu Rev Physiol. 2020 Feb 10;82:365-390. doi: 10.1146/annurev-physiol-021119-034650. Epub 2019 Nov 19. PMID: 31743079.
- FGF23 and Cardiovascular Risk. Prié D. Ann Endocrinol (Paris). 2021 Jun;82(3-4):141-143. doi: 10.1016/j.ando.2020.03.007. Epub 2020 Mar 10. PMID: 32950228.
- FGF23 predicts outcomes in heart failure but questions remain unanswered. Duran A, daSilva-deAbreu A, Joury A, Ventura HO. Int J Cardiol. 2021 Sep 1;338:145-146. doi: 10.1016/j.ijcard.2021.06.036. Epub 2021 Jun 19. PMID: 34157358.
- Paracrine Effects of FGF23 on the Heart. Front Endocrinol (Lausanne). Leifheit-Nestler M, Haffner D 2018 May 28;9:278. doi: 10.3389/fendo.2018.00278. PMID: 29892269; PMCID: PMC5985311.
- 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.
- The Measurement and Interpretation of Fibroblast Growth Factor 23 (FGF23) Concentrations. Calcif Tissue Int. Heijboer AC, Cavalier E. 2023 Feb;112(2):258-270. doi: 10.1007/s00223-022-00987-9. Epub 2022 Jun 4. PMID: 35665817; PMCID: PMC9859838.
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- Reliable Assay Kit
- Easy, Reliable NT-ProANP ELISA Kit
- Easy-to-Use System that Delivers the Desired Results
- Measuring Cell Proliferation with EZ4U
YOUR SATISFACTION IS OUR PRIORITY
Our goal is to meet your needs at every stage, starting from assay design and development, through manufacturing, validation and customer support. We have implemented a range of measures to achieve this:
- Ready-to-Use Assays
- Biomarker Detection in Real Samples
- Validation According to International Standards
- Qualified, Experienced Customer Service
- Flexibility
- Service Measurements
QUALITY is not just a word
Rest assured when using our products – we prioritize quality throughout the entire process from product development to manufacturing and quality control. Our goal is to ensure that the performance of our products meet the top quality standards.
Right after product development our kits go through a rigorous validation process in compliance with the international quality guidelines (FDA, EMEA, ICH). Each product is accompanied by a comprehensive validation report that can downloaded from our website www.bmgrp.com .
WE ARE HERE FOR YOU
The vast majority of Biomedica products is delivered and used without any issues. However, if you do encounter a problem or have a question, we are here to help. Our dedicated and qualified team will do their best to answer your questions and will be there for you. Due to the close collaboration between our team members in development and production, we are in a unique position to support our customers with all of the detailed information they may need.
Being scientists at heart, we are always happy to share our knowledge, give advice, and help our customers selecting biomarkers.
Role of C-Type Natriuretic Peptide (CNP) in bone growth and development
CNP is a member of the natriuretic peptide family. It acts as a paracrine hormone which is present in several tissues such as the cardiovascular system, brain and the endothelium. CNP controls various processes including blood pressure, water and mineral balance, and numerous metabolic functions (1). In 1995, CNP was first described as a potent regulator of bone remodeling, underlying its important role in humans (2).
C-Type Natriuretic Peptide Induces Bone Growth
Research has indicated that CNP is predominantly synthesized within the joint cartilage by chondrocytes, which are specialized cells primarily responsible for generating collagen and the extracellular matrix. As a result, the primary and well-established role of CNP is in the growth plate skeletal cartilage, where it plays a crucial role in promoting endochondral growth of the developing skeleton (3, 4).
What is the mechanism of bone growth?
The growth of bones is a complex process involving the formation and remodeling of bone tissue throughout the body. It is regulated by a diverse range of hormones, growth factors, and signaling pathways that interact together to maintain skeletal health and function.
Bone growth can be broadly classified into two types:
Longitudinal growth primarily takes place in the long bones of the body, such as femur and tibia. It is a process by which bones grow in length, predominantly occurring during childhood and adolescence. Longitudinal growth is facilitated by growth plates, which are cartilaginous areas located at the ends of long bones. As the bones elongate, the cartilage in the growth plates gradually undergoes ossification, transforming into bone tissue.
Appositional growth, on the other hand, is the process by which bones grow in thickness or diameter. This type of growth occurs throughout life and is regulated by a delicate balance between osteoblasts, cells responsible for bone formation and osteoblasts, cells involved in bone resorption and bone-resorbing cells named osteoclasts.
Numerous factors can influence bone growth, including genetics, nutrition, exercise, and hormonal equilibrium. Hormones such as growth hormone and sex hormones play crucial roles in regulating bone growth and development. One hormone that is of particular significance in this regard is C-type natriuretic peptide (CNP), which is essential for the regulation of bone growth.
Quantification of CNP and NT-proCNP in human blood samples
The measurement of biologically active CNP in human blood samples presents a challenge due to its dynamic role in bone growth, its rapid clearance and low circulating concentrations. However, the inactive, but more stable precursor molecule NT-proCNP, has proven to be a reliable alternative. The amino-terminal propeptide NT-proCNP, is synthesized in the growth plate, has a longer half-life and circulates in equimolar concentrations as CNP. Therefore, NT-proCNP is an excellent candidate for investigating the role of C-Type natriuretic Peptide in bone (1, 3).
A study comparing the measurement of CNP and NT-proCNP in human blood samples revealed that an NT-proCNP assay provides more consistent and reliable results, making it the preferred choice for clinical applications (5).
NT-proCNP can reliably be measured in serum and plasma samples with a conventional ELISA assay
BIOMEDICA – NT-proCNP ELISA (cat. no BI-20812)
- Full validation – following international quality guidelines
- For human and non-human samples (serum, plasma, cell culture, urine)
- Standard 96-well ELISA assay format- color coded and ready to use reagents
- Developed & manufactured by Biomedica
NT-proCNP serves as a biomarker of linear growth
Research studies in children has provided evidence showing a strong correlation between the levels of NT-proCNP in blood and the rate of linear growth throughout the entire growth process. In infancy, both males and females exhibit high levels of CNP and NT-proCNP, which subsequently decline in early childhood. However, during puberty, NT-proCNP levels rise again, followed by a decrease during adulthood. The peak levels of NT-proCNP align with the age at which peak height velocity occurs. As a result, the measurement of CNP syntheses through NT-proCNP in blood is highly indicative of linear growth in healthy children at all stages of development, making it an exceptional biomarker for monitoring linear growth (3, 6).
The role of NT-proCNP in bone diseases and genetic disorders
While the involvement of CNP in bone growth during development is well-established, its precise role in the adult skeleton remains uncertain. It is plausible that bone remodeling may contribute to increased plasma levels of CNP in children, given that CNP is expressed in osteoblasts and osteoclasts, which are the cells responsible for bone formation and bone degradation. Moreover, alternations in plasma CNP products have been linked to changes in bone turnover markers in adults (7),
CNP has emerged as a significant player in various types of skeletal dysplasia, a group of over 400 genetic disorders characterized by abnormal bone, joint, and cartilage development. Mutations in genes associated with CNP signaling have been identified in these conditions, including achondroplasia and hypochondroplasia, which are the most prevalent forms of dwarfism (8).
CNP has shown to be a promising therapeutic target for treating growth and skeletal disorders. Only recently, a variant of CNP was approved for treatment of achondroplasia (9). Ongoing clinical trials are currently investigating additional inhibitors of the CNP signaling pathway (10).
Related ELISA assay products
-NT-proANP (cat. no. BI-20492) – assay also suitable for preclinical applications (rat, mouse and other species) – 10µl sample volume
-NT-proBNP (cat. no. SK-1204) – CE-marked, for IVD use in EU
-NT-proBNP rat (cat. no. BI-1204R) – sample values provided
Literature
- Circulating products of C-type natriuretic peptide and links with organ function in health and disease. Prickett TC, A Espiner E. Peptides. 2020. 132:170363.
- C-type natriuretic peptide increases bone resorption in 1,25-dihydroxyvitamin D3-stimulated mouse bone marrow cultures. Holliday LS, Dean AD, Greenwald JE, Glucks SL. J Biol Chem. 1995. 11;270(32):18983-9.
- Plasma C-Type Natriuretic Peptide: Emerging Applications in Disorders of Skeletal Growth. Espiner E, Prickett T, Olney R. Horm Res Paediatr. 2018;90(6):345-357.
- Hormones and osteoporosis update. Effects of natriuretic peptides on endochondral bone growth. Clin Calcium. 2009. 19(7):1003-8. Yasoda A, Nakao K. Japanese. PMID: 19567998.
- Comparative measurement of CNP and NT-proCNP in human blood samples: a methodological evaluation. Kuehnl A, Pelisek J, Bruckmeier M, Safi W, Eckstein HH. J Negat Results Biomed. 2013. 1;12:7.
- Amino-terminal propeptide of C-type natriuretic peptide (NTproCNP) predicts height velocity in healthy children. Olney RC, Permuy JW, Prickett TC, Han JC, Espiner EA. Clin Endocrinol (Oxf). 2012. 77(3):416-22.
- C-type natriuretic peptide forms in adult hyperthyroidism: correlation with thyroid hormones and markers of bone turnover. Schouten BJ, Prickett TC, Hunt PJ, Richards AM, Geffner ME, Olney RC, Espiner EA. Clin Endocrinol (Oxf). 2012. 76(6):790-6.
- New developments in the management of achondroplasia. Högler W, Ward LM. Wien Med Wochenschr. 2020. 170(5-6):104-111.
- Expanding horizons of achondroplasia treatment: current options and future developments. Fafilek B, Bosakova M, Krejci P. Osteoarthritis Cartilage. 2022. 30(4):535-544.
- Emerging drug targets for achondroplasia. Savarirayan R. Expert Opin Ther Targets. 2022. 26(5):389-391.
We are happy to introduce our new brochure featuring our Quality Cytokine Assays “BIOMEDICA´s CYTOKINE ELISA kits”
Product Highlights
- Full validation package
- Ready-to-use prediluted standards
- Color coded reagents & controls included
- Kit calibration with WHO international standard
QUALITY CYTOKINE ELISA KITS FOR AFFORDABLE & EFFICIENT RESEARCH
human Cytokine ELISA Kits – developed & manufactured by Biomedica
- IL-6 (cat. no. BI-IL6) – high sensitivity – detectable levels
- VEGF (cat. no. BI-VEGF) – low sample volume – 10 µl – detecting all known VEGF isoforms
- ANGIOPOIETIN-2 (cat. no. BI-ANG2) / optimized assay range
Also available mouse/rat Angiopoietin-2 ELISA kit (cat. no. BI-ANG2MR) – only 5µl sample volume.
ABOUT CYTOKINES
Cytokines are critical cell signaling molecules that play important roles in the immune response and many other physiological processes. These proteins are produced by a wide variety of cell types that act on specific target cell receptors to trigger a range of biological responses.
Cytokines are involved in many aspects of the immune response, including inflammation, cell growth and differentiation, and cell death (apoptosis). Cytokines also regulate tissue repair and wound healing. Dysregulation of cytokine production and signaling may contribute to various diseases including autoimmune disorders, allergies, and cancer.
Some common cytokines include interleukins, tumor necrosis factor (TNF), and interferons.
Interleukin-6 (IL-6) is a pleiotropic cytokine that is largely involved in immunomodulatory processes. One of its roles is to respond to infections. As a pro-inflammatory cytokine, IL-6 activates the immune response, recruiting immune cells triggering B and T cell response. IL-6 dysregulation is associated with pathologies involving chronic inflammation, autoimmune diseases, and atherosclerosis. However, IL-6 also has beneficial anti-inflammatory and positive metabolic effects that are released during exercise coupled to a physical adaptation to intense training. In addition to its immune functions, IL-6 is involved in many other physiological processes, including bone remodeling and the nervous system.
Angiopoietin-2 (ANG2) is a protein that plays a critical role in regulating the development and remodeling of blood vessels, a process known as angiogenesis. ANG-2 is primarily produced by endothelial cells, which are cells that line the interior of blood vessels. Under normal physiological conditions the expression of ANG2 is low, which allows the blood vessels to undergo a rapid growth and remodeling. However, in pathological conditions, such as inflammation and cancer, ANG2 expression can be upregulated, leading to excessive angiogenesis and blood vessel destabilization.
Vascular endothelial growth factor (VEGF) is a protein mainly produced by endothelial cells. VEGF stimulates the growth and proliferation of endothelial cells, as well as the migration and differentiation of these cells into new blood vessels. VEGF plays a role in the development of cancer and certain ocular diseases, where it promotes the growth of new blood vessels that feed tumors or damage the retina.
There are several different isoforms of VEGF, each with different properties and functions. For example, VEGF-A is the most well-known cytokine of the VEGF family, and is primarily responsible for promoting angiogenesis. Other isoforms, such as VEGF-B and VEGF-C, have different roles in the body, such as regulating the growth of blood vessels in the heart and lymphatic system, respectively.
Related publications
Harnessing cytokines and chemokines for cancer therapy. Propper DJ, Balkwill FR. Nat Rev Clin Oncol. 2022 Apr;19(4):237-253. doi: 10.1038/s41571-021-00588-9. Epub 2022 Jan 7. PMID: 34997230.
Inflammatory Cytokines and Chemokines as Therapeutic Targets in Heart Failure. Hanna A, Frangogiannis NG. Cardiovasc Drugs Ther. 2020 Dec;34(6):849-863. doi: 10.1007/s10557-020-07071-0. Epub 2020 Sep 9. PMID: 32902739; PMCID: PMC7479403.
Around 7 out of 100,000 people are affected by primary malignant brain tumors. Glioblastoma multiforme (GBM) is the most common type of brain tumor. It grows rapidly and has a low prognosis of approximately 15 months. The mean age after diagnosis is 63 years (1, 2). Despite significant progress in treatment, there remains a critical need for novel treatment options for GBM.
Natural Malaria Substance – novel treatment option for brain tumors
Artemisinin, deriving from the plant Artemisia annua is a potent natural substance globally used to treat Malaria. It was discovered in the 1970s from Traditional Chinese Medicines and has since then saved millions of lives (3). Due to its cytotoxic properties it has not only been acknowledged for treating Malaria but also for its potential anticancer properties. With the discovery of Artemisinin and its derivates, researchers have been investigating the mechanisms on how these compounds work e.g. in inhibiting tumor cell proliferation, promoting apoptosis, disrupting caner invasion and metastasis, and preventing angiogenesis (4).
The natural malaria substance Artemisinin – a novel treatment option for brain tumors.
In a recent study using genome-wide screening, researchers have identified mitochondrial function, particularly the biosynthesis of porphyrin, as a crucial pathway responsible for Artemisinin´s cytotoxicity. The potential of this novel treatment option for human brain tumors is currently under investigation (5, 6).
EZ4U / MTT Cell viability assay (cat. no. BI-5000) – BIOMEDICA
The Biomedica EZ4U cell viability and cytotoxicity assay was employed in mammalian cell lines in the described study:
A whole-genome scan for Artemisinin cytotoxicity reveals a novel therapy for human brain tumors.
The non-toxic and non-radioactive assay EZ4U / MTT Cell viability assay is based on the conversion of the yellow tetrazolium salt to coloured soluble formazan, which is produced by mitochondrial enzymes. The quantity of formazan produced is in direct proportion to the number of viable, living cells present.
Assay Characteristics
- Method: Reduction of tetrazolium salt to coloured formazan
- Sample type cell culture medium
- Sample size 200 μl / test, 10×96 tests
- Detection limit depending on cell lines Incubation time 2 – 5 h
Click here to download our EZ4U “easy for you” – brochure
Literature
- Brain Tumors. Am J Med. McFaline-Figueroa JR, Lee EQ. 2018 Aug;131(8):874-882. doi: 10.1016/j.amjmed.2017.12.039. Epub 2018 Jan 31. PMID: 29371158.
- Rising Incidence of Glioblastoma Multiforme in a Well-Defined Population. Grech N, Dalli T, Mizzi S, Meilak L, Calleja N, Zrinzo A Cureus. 2020 May 19;12(5):e8195. doi: 10.7759/cureus.8195. PMID: 32572354; PMCID: PMC7302718.
- The discovery of artemisinin and the Nobel Prize in Physiology or Medicine. Su XZ, Miller LH. Sci China Life Sci. 2015 Nov;58(11):1175-9. doi: 10.1007/s11427-015-4948-7. PMID: 26481135; PMCID: PMC4966551.
- Antitumor Research on Artemisinin and Its Bioactive Derivatives. Zhang Y, Xu G, Zhang S, Wang D, Saravana Prabha P, Zuo Z. Nat Prod Bioprospect. 2018 Aug;8(4):303-319. doi: 10.1007/s13659-018-0162-1. Epub 2018 Apr 9. PMID: 29633188; PMCID: PMC6102173.
- A whole-genome scan for Artemisinin cytotoxicity reveals a novel therapy for human brain tumors. Taubenschmid-Stowers J, Orthofer M, Laemmerer A, Krauditsch C, Rózsová M, Studer C, Lötsch D, Gojo J, Gabler L, Dyczynski M, Efferth T, Hagelkruys A, Widhalm G, Peyrl A, Spiegl-Kreinecker S, Hoepfner D, Bian S, Berger W, Knoblich JA, Elling U, Horn M, Penninger JM. EMBO Mol Med. 2023 Mar 8;15(3):e16959. doi: 10.15252/emmm.202216959. Epub 2023 Feb 6. PMID: 36740985.
- Achilles heel of glioblastoma. JLP Health and its partners discover combinatorial treatment option for incurable brain tumors. Press Release, JLP Health GmbH, Vienna, Austria, 7 February 2023.
Bone metastases affect over 1.5 million cancer patients globally, making bones a favored metastatic site for solid tumors (1). The presence of skeletal metastases can significantly reduce the quality of life for individuals with advanced cancer, as weakened bones can cause pain, fractures, and increase the risk of mortality (2, 3).
Bones have numerous important functions which include structural support, mobility, hematopoiesis, and mineral storage (4). The health and performance of our bone tissue are overseen by a range of cell types, which include:
- Osteoblasts – cells responsible for creating new bone tissue
- Osteoclasts – cells responsible for breaking down bone tissue
- Osteocytes – cells within the bone that monitor mechanical loading and regulate the process of bone remodeling
Bone biology- cancer and bone
Cancer and Bone – bone a preferred target site for cancer metastasis
Bone is a favored destination for metastasis in specific types of cancer, whereby cancer cells detach from the primary tumor and disseminate throughout the body. Certain cancers, such as breast, prostate, kidney, lung, ovarian, and thyroid, are especially prone to spread to bone (5).
Cancer and Bone – the RANK/RANKL/OPG system
The RANK/RANKL/OPG system (receptor activator of the nuclear factor-κB ligand/ Osteoprotegerin) was identified more than 20 years ago and remains a widely researched topic until this day. The interaction between RANK and RANKL is essential for bone metabolism and osteoclast development. OPG acts as a decoy receptor for RANKL. By binding completely to RANKL, OPG obstructs the RANKL-RANK interaction, thereby blocking bone resorption. In addition to its role in regulating bone remodeling, the RANK/RANKL/OPG system is directly implicated in tumor cell development, particularly in the progression of breast and prostate cancer as well as leukemia (6-8).
Inhibiting RANK/RANKL signaling in human cancer
A fully humanized monoclonal antibody has been developed to counteract the effects of RANKL, which has received approval for treating bone loss conditions. The antibody functions by disrupting RANK signaling, preventing osteoclast activation and inhibiting bone resorption (6-8). More recently, inhibiting RANKL has been recognized as a significant checkpoint with the potential to influence anti-tumor response. Consequently, RANKL blockade has a direct impact on bone metastasis. Ongoing clinical and experimental trials are evaluating this emerging therapeutic approach (9).
Studies analyzing serum levels of OPG and RANKL
Serum concentrations of both OPG and soluble RANKL can be accessed via an enzyme-linked immunosorbent assay (ELISA). The predictive value of RANKL/OPG serum levels and disseminated tumor cells in breast cancer patients without metastasis was investigated in 509 patients with primary, nonmetastatic breast cancer. The results demonstrated that RANKL serum levels were significantly elevated in patients who developed bone metastases (10). A different study highlighted the role of OPG as a marker of breast cancer risk in women with a BRCA1 mutation. The authors suggested that OPG levels could be associated with disease risk, potentially serving as a marker for breast cancer risk and improving existing risk prediction models by identifying women at high risk of developing the disease (11).
How are circulating serum levels of Osteoprotegerin and soluble RANKL measured?
Both markers can easily be measured with a conventional ELISA assay.
- Osteoprotegerin (OPG) ELISA (cat. no. BI-20403) – day test, 20µl sample volume/well
- Soluble free RANKL ELISA (cat. no. BI-20462) – highly sensitive and reliable
– Widely cited in + 450 publications (citations for OPG, and RANKL)
– Extensively validated ELISA assays following international quality guidelines
High Quality ELISA kits – Developed & Manufactured by Biomedica
Related ELISA kits: DKK-1, Sclerostin, IL-6, VEGF, Angiopoietin-2
References
- Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells. Florencio-Silva R, Sasso GR, Sasso-Cerri E, Simões MJ, Cerri PS. Biomed Res Int. 2015;2015:421746. doi: 10.1155/2015/421746. Epub 2015 Jul 13. PMID: 26247020; PMCID: PMC4515490.
- Understanding the Bone in Cancer Metastasis. Fornetti J, Welm AL, Stewart SA. J Bone Miner Res. 2018 Dec;33(12):2099-2113. doi: 10.1002/jbmr.3618. Epub 2018 Nov 26. PMID: 30476357.
- Bone as a Preferential Site for Metastasis. JBMR Plus. Sowder ME, Johnson RW. 2019 Jan 15;3(3):e10126. doi: 10.1002/jbm4.10126. PMID: 30918918; PMCID: PMC6419612.
- Cancer to bone: a fatal attraction. Weilbaecher KN, Guise TA, McCauley LK. Nat Rev Cancer. 2011 Jun;11(6):411-25. doi: 10.1038/nrc3055. Epub 2011 May 19. PMID: 21593787; PMCID: PMC3666847.
- Bone metastasis: mechanisms, therapies, and biomarkers. Clézardin P, Coleman R, Puppo M, Ottewell P, Bonnelye E, Paycha F, Confavreux CB, Holen I. Physiol Rev. 2021 Jul 1;101(3):797-855. doi: 10.1152/ physrev.00012.2019. Epub 2020 Dec 24. PMID: 33356915.
- The Roadmap of RANKL/RANK Pathway in Cancer. Casimiro S, Vilhais G, Gomes I, Costa L. Cells. 2021 Aug 4;10(8):1978. doi: 10.3390/cells10081978. PMID: 34440747; PMCID: PMC8393235.
- RANKL biology: bone metabolism, the immune system, and beyond. Ono T, Hayashi M, Sasaki F, Nakashima T. Inflamm Regen. 2020 Feb 7;40:2. doi: 10.1186/s41232-019-0111-3. PMID: 32047573; PMCID: PMC7006158.
- RANKL and RANK in Cancer Therapy. Physiology (Bethesda). Onji M, Penninger JM. 2023 May 1;38(3):0. doi: 10.1152/physiol.00020.2022. Epub 2022 Dec 6. PMID: 36473204.
- The Role of the RANKL/RANK Axis in the Prevention and Treatment of Breast Cancer with Immune Checkpoint Inhibitors and Anti-RANKL. Simatou A, Sarantis P, Koustas E, Papavassiliou AG, Karamouzis MV. Int J Mol Sci. 2020 Oct 14;21(20):7570. doi: 10.3390/ijms21207570. PMID: 33066388; PMCID: PMC7590202.
- Prognostic Value of RANKL/OPG Serum Levels and Disseminated Tumor Cells in Nonmetastatic Breast Cancer. Rachner TD, Kasimir-Bauer S, Göbel A, Erdmann K, Hoffmann O, Browne A, Wimberger P, Rauner M, Hofbauer LC, Kimmig R, Bittner AK. Clin Cancer Res. 2019 Feb 15;25(4):1369-1378. doi: 10.1158/1078-0432.CCR-18-2482. Epub 2018 Nov 13. PMID: 30425091.
- Delineating the role of osteoprotegerin as a marker of breast cancer risk among women with a BRCA1 mutation. Park SS, Uzelac A, Kotsopoulos J. Hered Cancer Clin Pract. 2022 Apr 13;20(1):14. doi: 10.1186/s13053-022-00223-3. PMID: 35418083; PMCID: PMC9008947.
We offer custom analytical testing services for the measurement of your samples. ANALYTICAL SERVICES – BIOMEDICA – reliable and flexible:
METHODS: ELISA & Luminex Assays, microRNA Analysis, and Glycan Profiling.
Advantages of Using Biomedica Analytical Testing Services:
- Flexibility: customized according to your project needs
- Expertise: experienced laboratory staff
- Quality: high quality equipment
- Speed: rapid turn-around time to meet your deadlines
- Results: verified and comprehensive results presented in an analytical report
Check out our ELISA and Luminex Workflow chart and our microRNA Service Details
Biomedica offers a broad range of high quality RNA services performed by experts according to GLP standards. These services include:
- RNA extraction: Biofluids including serum, plasma, and extracellular vesicles. Cells and tissues – the quality control of total RNA is carried out utilizing bioanalyser chips.
- Next-generation sequencing- NGS.
- RT-qPCR.
- We also analyse cell-type specific microRNA/mRNA in complex tissues and offer custom analysis of microRNA signatures.
- Finally, we carry out the analysis of established microRNA signatures to predict fracture risk, platelet function, and toxicity.
- Biomedica and TAmiRNA
Biomedica Analytical Services – reliable and flexible
We can measure any kind of selected biomarker on your “wish” list by ELISA (enzyme linked immunosorbent assay) for clinical and preclinical samples e.g.
-
- Clinical samples (serum, plasma, urine, cell culture supernatants)
- Pre-clinical samples (e.g. NT-proBNP or NT-proANP measurement in mouse, rat, rabbit, or other species)
- Custom applications – contact us
Chronic Kidney Disease (CKD) affects more than 10% of the general population worldwide (1). It is characterized by kidney fibrosis, a progressive process that destroys the kidney (2). An effective treatment to stop the progression of CKD is still lacking. Scientists have now discovered a potential mean to treat CKD by inhibiting Angiopoietin-2 (ANG2), a vascular growth factor (3). Angiopoietin-2 is a potential new treatment target for kidney fibrosis in CKD.
Angiopoietin-2 a new treatment target for kidney fibrosis in CKD
Patients with chronic kidney disease (CKD) have increased plasma levels of Angiopoietin-2 (ANG2). Studies have shown that ANG2 induces kidney injury and fibrosis in patients with CKD as well as in mouse models of kidney disease (3). Preventing the progression of renal fibrosis by blocking Angiopoietin-2 could be a new approach in treating chronic kidney disease-associated pathologies.
Based on data of the recent study from Chang et al., on the application of an Angiopoietin-2 inhibitor to mouse models of progressive kidney disease, the scientists found a profound inhibitory effects of ANG2 inhibition on macrophage infiltration and fibrosis (3).
Future clinical studies will be required to investigate the therapeutic potential on the protective effect of Angiopoietin-2 inhibition on progressive kidney disease. Read more: Angiopoietin-2 inhibition attenuates kidney fibrosis by hindering chemokine C-C motif ligand 2 expression and apoptosis of endothelial cells.
BIOMEDICA developed two assays for the accurate measurement of ANGIOPOIETIN-2
Mouse / rat ANGIOPOIETIN-2 ELISA (cat. no. BI-ANG2MR)
- only 5µl sample volume /well
- no predilution of samples required
- kit control included
- sample values provided
Human ANGIOPOIETIN-2 ELISA (cat. no. BI-ANG2)
- only 20µl sample volume /well
- the assay is optimized for clinical samples – sample values provided
- ready to use standards and controls included
References
1. Prevalence, outcomes, and cost of chronic kidney disease in a contemporary population of 2·4 million patients from 11 countries: The CaReMe CKD study. Sundström J, Bodegard J, Bollmann A, Vervloet MG, Mark PB, Karasik A, Taveira-Gomes T, Botana M, Birkeland KI, Thuresson M, Jäger L, Sood MM, VanPottelbergh G, Tangri N; CaReMe CKD Investigators. Lancet Reg Health Eur. 2022 Jun 30;20:100438. doi: 10.1016/j.lanepe.2022.100438. PMID: 36090671; PMCID: PMC9459126.
2. Fibrosis in Chronic Kidney Disease: Pathogenesis and Consequences. Panizo S, Martínez-Arias L, Alonso-Montes C, Cannata P, Martín-Carro B, Fernández-Martín JL, Naves-Díaz M, Carrillo-López N, Cannata-Andía JB. Int J Mol Sci. 2021 Jan 2;22(1):408. doi: 10.3390/ijms22010408. PMID: 33401711; PMCID: PMC7795409.
3. Angiopoietin-2 inhibition attenuates kidney fibrosis by hindering chemokine C-C motif ligand 2 expression and apoptosis of endothelial cells. Chang FC, Liu CH, Luo AJ, Tao-Min Huang T, Tsai MH, Chen YJ, Lai CF, Chiang CK, Lin TH, Chiang WC, Chen YM, Chu TS, Lin SL. Kidney Int. 2022 Oct;102(4):780-797. doi: 10.1016/j.kint.2022.06.026. Epub 2022 Aug 4. PMID: 35934136.
Abstract
Plasma levels of angiopoietin-2 are increased in patients with chronic kidney disease (CKD). Moreover, mouse models of progressive kidney disease also demonstrate increased angiopoietin-2 in both plasmas and kidneys. The role of dysregulated angiopoietins in the progression of kidney disease has not been thoroughly investigated. Here, we found in a cohort of 319 patients with CKD that plasma angiopoietin-2 and angiopoietin-2/angiopoietin-1 ratios were positively associated with the development of kidney failure. In mice with progressive kidney disease induced by either ureteral obstruction or ischemia-reperfusion injury, overexpression of human angiopoietin-1 in the kidney tubules not only reduced macrophage infiltration in the initial stage post-injury but also attenuated endothelial cell apoptosis, microvascular rarefaction, and fibrosis in the advanced disease stage. Notably, angiopoietin-1 attenuated chemokine C-C motif ligand 2 (CCL2) expression in the endothelial cells of the fibrosing kidneys, and these protective effects led to attenuation of functional impairment. Mechanistically, angiopoietin-1 reduced CCL2-activated macrophage migration and protected endothelial cells against cell apoptosis induced by angiopoietin-2 and Wnt ligands. Based on this, we applied L1-10, an angiopoietin-2 inhibitor, to the mouse models of progressive kidney disease and found inhibitory effects on macrophage infiltration, microvascular rarefaction, and fibrosis. Thus, we defined the detrimental impact of increased angiopoietin-2 on kidney survival of patients with CKD which appears highlighted by angiopoietin-2 induced endothelial CCL2-activated macrophage infiltration and endothelial cell apoptosis in their kidneys undergoing fibrosis.
Further reading
New therapeutic targets in chronic kidney disease progression and renal fibrosis. Rayego-Mateos S, Valdivielso JM. Expert Opin Ther Targets. 2020 Jul;24(7):655-670. doi: 10.1080/14728222.2020.1762173. Epub 2020 May 18. PMID: 32338087.
The International Day of Happiness has been initiated by the United Nations to spread awareness of the importance of happiness in the lives of people around the world (1). Happiness and health are closely tied together and affect one another.
Happiness and Health
Numerous studies have found that happiness is linked to a strong immune system and a better general health (2). Reducing risk factors e.g., tobacco, alcohol, low-nutrition foods and beverages are only some strategies to reduce disease burden (3).
Studying biomarkers may help to understand the mechanism on how the disease originates and could improve diagnosis and disease prognosis (4).
BIOMEDICA specializes on the development of cutting-edge biomarker assays for clinical research.
Biomedica ELISA kits by research area
- Bone Metabolism
- Cardiovascular
- Cell Proliferation
- Immunology
- Infectious Disease
- Metabolic Disease
- Infection
- Nephrology and Transplant
- Neurology
- Oncology
- Oxidative Stress
- Cytokines
High quality ELISA kits- developed and manufactured by Biomedica
References
- International Day of Happiness – the United Nations
- Happiness and Health Annu Rev Public Health. Steptoe A. 2019 Apr 1;40:339-359. doi: 10.1146/annurev-publhealth-040218-044150. Epub 2019 Jan 2. PMID: 30601719. Full text review
Abstract
Research into the relationship between happiness and health is developing rapidly, exploring the possibility that impaired happiness is not only a consequence of ill-health but also a potential contributor to disease risk. Happiness encompasses several constructs, including affective well-being (feelings of joy and pleasure), eudaimonic well-being (sense of meaning and purpose in life), and evaluative well-being (life satisfaction). Happiness is generally associated with reduced mortality in prospective observational studies, albeit with several discrepant results. Confounding and reverse causation are major concerns. Associations with morbidity and disease prognosis have also been identified for a limited range of health conditions. The mechanisms potentially linking happiness with health include lifestyle factors, such as physical activity and dietary choice, and biological processes, involving neuroendocrine, inflammatory, and metabolic pathways. Interventions have yet to demonstrate substantial, sustained improvements in subjective well-being or direct impact on physical health outcomes. Nevertheless, this field shows great potential, with the promise of establishing a favorable effect on population health.
- Association of Healthy Lifestyle With Years Lived Without Major Chronic Diseases.Nyberg ST, Singh-Manoux A, Pentti J, .. Batty GD, Kivimäki M. JAMA Intern Med. 2020 May 1;180(5):760-768. doi: 10.1001/jamainternmed. 2020.0618. PMID: 32250383; PMCID: PMC7136858.
- Role of Biomarkers in Health Care. Jain KK. The Handbook of Biomarkers. 2010 Jan 20:115–88. doi: 10.1007/978-1-60761-685-6_5. PMCID: PMC7123449.
World Kidney Day – March 9, 2023 – raising awareness of the importance of our kidneys
Around 1 in 10 people suffer from chronic kidney disease (CKD), with more than 800 million individuals being affected worldwide. CKD is a progressive disease in which the kidneys gradually lose their function over time. If detected early, medication and changes in lifestyle may help to prevent or slow down CKD progression.
What are the risk factors for CKD?
Older age (+60 years), diabetes, high blood pressure, heart disease, obesity and some medications are some known risk factors for kidney disease.
How can we keep our kidneys healthy?
Nutrition, exercise, sufficient fluid intake are only some examples on how to keep our kidneys healthy. Valuable information can be found on the following websites :
“The International Society of Nephrology – ISN”
“International Federation of Kidney Foundations – IFKF”
BIOMEDICA – Biomarker ELISA kits for clinical research in kidney disease
check out our Brochure – Biomarkers in Clinical Nephrology
ROBUST & RELIABLE ASSAYS
- Fully validated according to international quality guidelines
- Widely cited in over 1500 publications
FGF23 (Fibroblast growth factor 23) Vanin-1, Endostatin, Sclerostin, Osteoprotegerin, Angiopoietin-2, IL-6, VEGF
Biomedica Quality ELISA kits
LITERATURE
Plant-based diets for prevention and management of chronic kidney disease. Joshi S, Hashmi S, Shah S, Kalantar-Zadeh K. Curr Opin Nephrol Hypertens. 2020 Jan;29(1):16-21. doi: 10.1097/MNH.0000000000000574. PMID: 31725014.
Abstract
Purpose of review: Plant-based diets have been used with growing popularity for the treatment of a wide range of lifestyle-related diseases, including diabetes, hypertension, and obesity. With the reinvigoration of the dietary management of chronic kidney disease (CKD) and the use of low protein diets for secondary prevention of CKD to delay or prevent dialysis therapy, there is an increasing interest in the potential role of plant-based diets for these patients.
Recent findings: Recently, a body of evidence related to the role of plant-based diets in preventing CKD has reemerged. Several observational studies have shown that red and processed meat have been associated with increased risk of CKD as well as faster progression in those with preexisting CKD. In several substitution analyses, replacement of one serving of red and/or processed meat has been linked with sizable reductions in CKD risk. Although limited, experimental trials for the treatment of metabolic acidosis in CKD with fruits and vegetables show outcomes comparable to oral bicarbonate. The use of plant-based diets in CKD may have other benefits in the areas of hypertension, weight, hyperphosphatemia, reductions in hyperfiltration, and, possibly, mortality. The risk of potassium overload from plant-based diets appears overstated, mostly opinion-based, and not supported by the evidence. Plant-based diets are generally well tolerated and provide adequate protein intake, including essential amino acids as long as the diet is correctly implemented.
Summary: Plant-based diets should be recommended for both primary and secondary prevention of CKD. Concerns of hyperkalemia and protein inadequacy related to plant-based diets may be outdated and unsupported by the current body of literature. Healthcare providers in general medicine and nephrology can consider plant-based diets as an important tool for prevention and management of CKD.
Exercise and Kidney Disease Prevention: Walk This Way. Seliger S, Weiner DE. Am J Kidney Dis. 2022 Oct;80(4):552-554. doi: 10.1053/j.ajkd.2022.07.001. Epub 2022 Jul 21. PMID: 35872228.
Raising awareness, screening and prevention of chronic kidney disease: It takes more than a village. Hsiao LL. Nephrology (Carlton). 2018 Oct;23 Suppl 4:107-111. doi: 10.1111/nep.13459. PMID: 30298651.
Abstract
Chronic kidney disease (CKD) is a major public health problem worldwide. Its prevalence and incidence are increasing, particularly among the ethnic minority populations. Diabetes, hypertension and obesity have been the three major aetiologies for CKD in all developed countries. While diabetes and hypertension remain the major causes of CKD in developing countries, environmental pollution, pesticides, water, analgesic abuse and herbal medications are common causes in these regions. Rapid urbanization and globalization are thought to be the contributing factors to rising prevalence and incidents of CKD. Despite the rising prevalence of CKD, disease awareness remains profoundly low. Worldwide, only 6% of the general population and 10% of the high-risk population are aware of their CKD statuses. Health screenings have been shown to be effective in improving the incidence of ESRD. However, currently there is no effective tool to assess and evaluate the awareness objectively.
Microbiome-metabolome reveals the contribution of gut-kidney axis on kidney disease. Chen YY, Chen DQ, Chen L, Liu JR, Vaziri ND, Guo Y, Zhao YY. J Transl Med. 2019 Jan 3;17(1):5. doi: 10.1186/s12967-018-1756-4. PMID: 30602367; PMCID: PMC6317198.
Acute kidney injury (AKI) – also called acute renal failure – occurs when the kidneys suddenly fail to function due to an injury medication, or an infection. It happens within a few hours or days and is usually accompanied with other medical conditions e.g. blood vessel blockage, diabetes, heart failure, kidney and liver disease, hospitalization (ICU) and other.
FGF23 in Acute Kidney Injury
Fibroblast growth factor 23 (FGF23) is a bone derived hormone that regulates renal phosphate excretion in the kidney. In kidney disease, when the function of the kidney declines, serum phosphate levels rise which subsequently leads to the secretion of FGF-23. High phosphate levels are also common in patients with acute kidney injury (AKI) (1).
FGF23 marker of adverse outcomes in acute kidney injury
Fibroblast growth factor 23 (FGF23) levels rise rapidly with acute kidney injury and are associated with the requirement for renal replacement therapy (1-4). FGF-23 levels also have prognostic utility as shown in a large study in over 1500 patients with AKI (3).
Most studies measuring elevated FGF23 levels in AKI patients are performed using FGF23 (C-terminal) assays, which detect intact and C-terminal FGF23. Although the results mirror an increase of FGF23 production they may not necessarily reflect the bioactivity of FGF23 (5).
Quantifying circulating FGF23 levels
Circulating FGF23 levels include the bioactive intact hormone (iFGF23) and the inactive N-terminal and C-terminal fragments. FGF23 can be measured with two commercially available assay types (6). The C-terminal FGF23 assay captures both intact and the c-terminal fragments of FGF23, which result after cleavage. The intact FGF23 assay utilizes antibodies that are located in the N-terminal and in the C-terminal region of the FGF23 hormone, thus capturing only biologically active intact FGF23.
Learn more: FGF23 – an Overview
BIOMEDICA offers quality FGF23 assays for serum & plasma samples
FGF23 (c-terminal) ELISA, cat. no. BI-20702
FGF23 intact ELISA, cat no. BI-20700
- developed & manufactured by Biomedica , Austria
- fully validated
- numerous top journal citations
Literature
- Fibroblast Growth Factor 23 and Klotho in AKI. Christov M, Neyra JA, Gupta S, Leaf DE. Semin Nephrol. 2019 Jan;39(1):57-75. doi: 10.1016/j.semnephrol.2018.10.005. PMID: 30606408.
- Fibroblast Growth Factor 23 Regulation and Acute Kidney Injury. Zhou W, Simic P, Rhee EP. Nephron. 2022;146(3):239-242. doi: 10.1159/000517734. Epub 2021 Jul 20. PMID: 34284404; PMCID: PMC8770696.
- Fibroblast growth factor 23 associates with death in critically ill patients. Leaf DE, Siew ED, Eisenga MF, Singh K, Mc Causland FR, Srivastava A, Ikizler TA, Ware LB, Ginde AA, Kellum JA, Palevsky PM, Wolf M, Waikar SS, Am Clin J Am Soc Nephrol. 2018. 13(4):531–41.
- FGF-23 levels in patients with AKI and risk of adverse outcomes. Leaf DE, Wolf M, Waikar SS, Chase H, Christov M, Cremers S, Stern L. Clin J Am Soc Nephrol. 2012. 7(8):1217-23.
- Fibroblast Growth Factor 23 and αKlotho in Acute Kidney Injury: Current Status in Diagnostic and Therapeutic Applications. Neyra JA, Hu MC, Moe OW. Nephron. 2020;144(12):665-672. doi: 10.1159/000509856. Epub 2020 Aug 25. PMID: 32841947; PMCID: PMC7708396.
- The Measurement and Interpretation of Fibroblast Growth Factor 23 (FGF23) Concentrations. Heijboer AC, Cavalier E. Calcif Tissue Int. 2023. 112(2):258-270.
NEW – Rat NT-proBNP ELISA assay
quantitative, reliable and robust for translational research and drug discovery.
Rat NT-proBNP ELISA assay │ BI-1204R
features & benefits
- 10 µl / well, serum or plasma
- kit control included
- sample values provided
NT-proANP ELISA assay │BI-20892
features & benefits
- 10 µl / well, serum or plasma
- widely cited as cardiovascular safety biomarker in rats
“cross-laboratory comparison study detecting serum NT-proANP in rats with the Biomedica NT-proANP ELISA to be technically adequate with acceptable intra- and inter-assay and inter-laboratory precision and accuracy (Vinken et al., 2016).”
All assays are developed and manufactured by Biomedica!
NT-proBNP & NT-proANP in drug-induced cardiac hypertrophy
The cardiac biomarkers NT-proBNP and NT-proANP are predictive of left ventricular hypertrophy (LVH) and systolic dysfunction in humans (1, 2).
In preclinical settings they have successfully been used to detect cardiotoxicity (3). NT-proBNP and NT-proANP have shown to be useful tools that help to improve the detection of cardiovascular injury early in drug development (4).
REFERENCES
- Circulating N-terminal pro-atrial natriuretic peptide is an independent predictor of left ventricular hypertrophy in the general population. The Tromsø Study. Schirmer H, Omland T. Eur Heart J. 1999 May;20(10):755-63. doi: 10.1053/euhj.1998.1396. Erratum in: Eur Heart J 1999 Oct;20(19):1439. PMID: 10329067.
- An association between N-terminal pro-brain natriuretic protein level and risk of left ventricular hypertrophy in patients without heart failure. Huang L, Huang L, Yu J, Wu X, Zhao J Exp Ther Med. 2020 May;19(5):3259-3266. doi: 10.3892/etm.2020.8598. Epub 2020 Mar 12. PMID: 32266021; PMCID: PMC7132238.
- Cardiac Hypertrophy Working Group of the Predictive Safety Testing Consortium. Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy. Dunn ME, Manfredi TG, Agostinucci K, Engle SK, Powe J, King NM, Rodriguez LA, Gropp KE, Gallacher M, Vetter FJ, More V, Shimpi P, Serra D, Colton HM Toxicol Pathol. 2017 Feb;45(2):344-352. doi: 10.1177/0192623316634231. Epub 2016 Jul 11. PMID: 27102652.
- Integrated approach to early detection of cardiovascular toxicity induced by a ghrelin receptor agonist. Stokes AH, Falls JG, Yoon L, Cariello N, Faiola B, Colton HM, Jordan HL, Berridge BR. Int J Toxicol. 2015 Mar-Apr;34(2):151-61. doi: 10.1177/1091581815573029. Epub 2015 Feb 26. PMID: 25722321.
Valvular heart disease is a leading cause of cardiovascular morbidity. Transcatheter aortic valve replacement (TAVR) is a minimally invasive procedure that replaces the aortic valve in patients with aortic stenosis. Mineral homeostasis, the process that regulates the body’s levels of calcium and phosphorus, plays an important role in the progression of cardiovascular diseases, including calcific aortic valve stenosis. FGF23 is a bone-derived phosphotropic hormone that regulates phosphate and vitamin D metabolism. FGF23 has been shown to be an independent risk factor for CV morbidity and mortality.
FGF23 is a novel risk factor for patients undergoing TAVR
A study by Mirna et al. evaluated the predictive potential of both C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) for adverse outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) with regard to renal function. Patients were followed up at 12 months.
The authors demonstrated:
- significant association of high cFGF23 levels with mortality in patients with an estimated glomerular filtration rate (eGFR) ≥45 ml/min/1.73m².
- patients with cFGF23 levels above the cut-off of 6.82 pmol/l had a worse 1-year-mortality
- cFGF23 could be a novel risk factor for patients undergoing TAVR with eGFR ≥45ml/min/1.73m².
FGF23 (C-terminal) and FGF23 intact were both measured with an ELISA assay from BIOMEDICA.
Assay Highlights
- full validation package
- for serum and plasma
- +50 international references
LITERATURE
Mirna M, Lauten A, Jirak P, Rezar R, Wernly B, Paar V, Felder TK, Hoppe UC, Motloch LJ, Jung C, Alushi B, Lichtenauer M, Salmhofer H. Eur J Intern Med. 2021. 85:98-107. doi: 10.1016/j.ejim.2020.09.022. Epub 2020 Nov 13. PMID: 33191056.
Abstract
Introduction: Serum levels of FGF23 have been associated with adverse outcomes in cardiovascular diseases in patients with and without impaired renal function. Hence, this study aimed to explore the prognostic relevance of intact FGF23 (iFGF23) and its derivate C-terminal FGF23 (cFGF23) in patients undergoing transcatheter aortic valve replacement (TAVR) with regard to renal function.
Methods: A total of 274 patients undergoing transfemoral TAVR were enrolled in this study. Blood samples were obtained preinterventionally and analyzed for iFGF23 and cFGF23 by means of enzyme linked immunosorbent assay (ELISA). Follow-up was obtained for 12 months.
Results: Serum levels of cFGF23 and iFGF23 both correlated positively with serum creatinine and inversely with estimated glomerular filtration rate (eGFR). Cox regression analysis revealed a significant association of cFGF23 with 1-year-mortality in patients with eGFR ≥45ml/min/1.73m², but not in patients with an eGFR <45ml/min/1.73m². A cut-off was calculated for cFGF23 (6.82 pmol/l) and patients with eGFR ≥45ml/min/1.73m² were retrospectively divided into two groups (above/below cut-off). Patients above the cut-off had a significantly worse 1-year-mortality than patients below the cut-off (33.3% vs. 19.6%; OR 2.05 (95%CI 1.03-4.07), p= 0.038). The association of cFGF23 with 1-year-mortality in patients with eGFR ≥45ml/min/1.73m² remained statistically significant even after correction for possible confounders in a multivariate Cox regression analysis.
Conclusion: cFGF23 could be an individual risk factor for mortality in patients undergoing TAVR with an eGFR ≥45ml/min/1.73m².
The natriuretic peptides NT-proBNP & NT-proANP
Cardiac Biomarkers – kits for clinical & preclinical use
NT-proBNP is released in the heart in response to cardiac wall stretch or pressure overload. It is considered as the gold standard in heart failure and is useful for both diagnosis and prognosis (1).
NT-proANP is synthesized and stored in atrial myocytes in response to increased intra-atrial pressure. Elevated circulating levels of NT-proANP are associated with heart failure resulting from increased mechanical stress in the heart during hypertension. In population-based studies, elevated plasma NT-pro-ANP levels predicted the risk of cardiovascular events and death ( 2).
Cardiac Biomarkers – kits for clinical & preclinical use
Natriuretic peptides in pre-clinical models as cardiac toxicity biomarkers
Biomarkers are also a valuable tool to explore drug effects in pre-clinical models. The natriuretic peptide NT-proANP has successfully been validated as a cardiovascular safety biomarker in rodents (3). An additional cardiac toxicity biomarker in drug development is NT-proBNP supporting the use of natriuretic peptides to investigate drug-induced cardiac hypertrophy (4, 5).
Biomedica offers a range of top quality ELISA kits for your clinical & preclinical research
- NT-proBNP – human (CE-marked in EU) (#SK-1204)
- NT-proBNP – rat (new!) (#BI-1204R)
- NT-proANP – human, rodent (#BI-20892) citations rat/mouse
- widely cited in over 400 publications
- kit validation follows international quality guidelines
LITERATURE
- NT-proBNP: The Gold Standard Biomarker in Heart Failure. McKie PM, Burnett JC Jr. J Am Coll Cardiol. 2016; 6;68(22):2437-2439.
- Plasma natriuretic peptide levels and the risk of cardiovascular events and death. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, Wolf PA, Vasan RS. N Engl J Med. 2004; 12;350(7):655-63.
- Cross-laboratory analytical validation of the cardiac biomarker NT-proANP in rat. Vinken P, Reagan WJ, Rodriguez LA, Buck WR, Lai-Zhang J, Goeminne N, Barbacci G, Liu R, King NM, Engle SK, Colton H. Pharmacol Toxicol Methods. 2016; 77:58-65.
- Evaluation of Cardiac Toxicity Biomarkers in Rats from Different Laboratories. Kim K, Chini N, Fairchild DG, Engle SK, Reagan WJ, Summers SD, Mirsalis JC – Cardiac Hypertrophy Working Group of the Predictive Safety Testing Consortium. Toxicol Pathol. 2016; 44(8):1072-1083.
- Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy. Dunn ME, Manfredi TG, Agostinucci K, Engle SK, Powe J, King NM, Rodriguez LA, Gropp KE, Gallacher M, Vetter FJ, More V, Shimpi P, Serra D, Colton HM – Cardiac Hypertrophy Working Group of the Predictive Safety Testing Consortium. Toxicol Pathol. 2017; 45(2):344-352.
For use in preclinical models – cardiotoxicity biomarkers
Rat NT-proBNP ELISA , cat. no. BI-1204R
NT-proANP ELISA independently validated for rat, cat. no. BI-20892
February is “Heart Month” raising awareness about heart disease. Biomarker research has revolutionized on how heart diseases are diagnosed and treated. Ongoing research on newer exploratory protein biomarkers may shed light into the complex mechanisms that drive the disease process.
Novel Biomarkers for Heart Disease
BIG ENDOTHELIN-1, ENDOSTATIN, FGF23, LRG
Big Endothelin-1 (Big ET-1) is a vasoconstrictor peptide and is the precursor of Endothelin-1 (ET-1) the biologically active form. Elevated concentrations provide an independent indicator of heart failure in congestive heart disease (1). Big ET-1 has a longer half-life than ET-1 and circulates in equimolar amounts as ET-1, making it a more reliable biomarker.
Endostatin is a degradation product of collagen XVIII and is an extracellular matrix protein. Endostatin plays an essential role in the pathogenesis of chronic kidney and heart diseases (2). A study in two community-based cohorts of elderly showed an association of high serum endostatin levels with left ventricular dysfunction and an increased heart failure risk (3).
Fibroblast growth factor-23 (FGF23) is a hormone that regulates phosphate metabolism. FGF23 has been suggested as a novel candidate biomarker of cardiovascular risk. High circulating FGF23 levels have been associated with adverse cardiovascular outcomes such as heart failure and arrhythmias (4).
Leucine-riche alpha-2-glyoprotein (LRG) is a secreted protein that plays an important role in pathogenic ocular neovascularization. LRG is also involved in multiple conditions including cardiovascular disease, diabetes, inflammatory disorders, and cancer. A recent study demonstrated that LRG accurately identify patients with heart failure stronger than BNP, independent of age, sex, and creatinine (5, 6).
NOVEL BIOMARKERS FOR HEART DISEASE
Biomedica offers a range of top quality ELISA kits for your clinical & preclinical research.
-Big Endothelin-1 (#BI-20082H)
-Endostatin (#BI-20742)
-Endostatin mouse/rat (#BI-20742MR)
-FGF23 intact (#BI-20700)
-FGF23 c-terminal (#BI-20702)
-LRG (#BI-LRG)
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LITERATURE
- Plasma concentration of big endothelin-1 and its relation with plasma NT-proBNP and ventricular function in heart failure patients. Rivera M et al., Rev Esp Cardiol. 2005; 58(3):278-84.
- Endostatin in Renal and Cardiovascular Diseases. Li M et al., Kidney Dis. 2021; 9;7(6):468-481.
- Circulating endostatin and the incidence of heart failure. Ruge T et al., 2018; 52(5):244-249.
- Fibroblast Growth Factor 23 and Long-Term Cardiac Function: The Multi-Ethnic Study of Atherosclerosis. Patel RB et al., Cardiovasc Imaging. 2020; 13(11):e011925.
- Proteomic analysis of coronary sinus serum reveals leucine-rich α2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure. Watson CJ et al., Circ Heart Fail. 2011; 4(2):188-97.
- Serum biomarker discovery related to pathogenesis in acute coronary syndrome by proteomic approach Shin M et al.,Biosci Rep. 2021; 25;41(6):BSR20210344.
Widely cited non-radioactive EZ4U – Cell Proliferation & Cytotoxicity Assay – single step incubation for use on living cells
The Biomedica EZ4U cell proliferation and cytotoxicity assay was highlighted in a recent study investigating the cytotoxicity of drug combinations tested against different pancreatic cell lines. Learn more: Cytotoxicity of combinations of the pan-KRAS SOS1 inhibitor BAY-293 against pancreatic cancer cell lines.
Pancreatic ductal adenocarcinomas (PDACs), the most prevalent pancreatic cancer, is highly aggressive with a 5-year overall survival rate of less than 8%. Late detection, it´s metastatic spread and the resistance to chemotherapy are among some of the factors responsible for poor patient outcome. The PDAC incidence rate is increasing and is particularly related to the general aging of our society. Furthermore, life style habits that include abuse of alcohol and tobacco as well as obesity and type 2 diabetes increases the risk for various types of cancer including PDAC.
EZ4U – Cell Proliferation & Cytotoxicity Assay (cat.no. BI-5000)
-Non-radioactive & non-toxic assay
-Reliable & Sensitive
-Convenient single-step incubation – for use on living cells
-Widely cited in more than 230 publications
BROCHURE – EZ4U cell proliferation and cytotoxicity assay
FURTHER READING
Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy.
World J Gastrointest Oncol. Sarantis P, Koustas E, Papadimitropoulou A, Papavassiliou AG, Karamouzis MV. 2020 Feb 15;12(2):173-181. doi: 10.4251/wjgo.v12.i2.173. PMID: 32104548; PMCID: PMC7031151.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, with an average 5-year survival rate of less than 10%. Unfortunately, the majority of patients have unresectable, locally advanced, or metastatic disease at the time of diagnosis. Moreover, traditional treatments such as chemotherapy, surgery, and radiation have not been shown to significantly improve survival. Recently, there has been a swift increase in cancer treatments that incorporate immunotherapy-based strategies to target all the stepwise events required for tumor initiation and progression. The results in melanoma, non-small-cell lung cancer and renal cell carcinoma are very encouraging. Unfortunately, the application of checkpoint inhibitors, including anti-CTLA4, anti-PD-1, and anti-PD-L1 antibodies, in pancreatic cancer has been disappointing. Many studies have revealed that the PDAC microenvironment supports tumor growth, promotes metastasis and consists of a physical barrier to drug delivery. Combination therapies hold great promise for enhancing immune responses to achieve a better therapeutic effect. In this review, we provide an outline of why pancreatic cancer is so lethal and of the treatment hurdles that exist. Particular emphasis is given to the role of the tumor microenvironment, and some of the latest and most promising studies on immunotherapy in PDAC are also presented.
Orth M, Metzger P, Gerum S, Mayerle J, Schneider G, Belka C, Schnurr M, Lauber K. Radiat Oncol. 2019 Aug 8;14(1):141. doi: 10.1186/s13014-019-1345-6. PMID: 31395068; PMCID: PMC6688256.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with poor prognosis and rising incidence. Late detection and a particularly aggressive biology are the major challenges which determine therapeutic failure. In this review, we present the current status and the recent advances in PDAC treatment together with the biological and immunological hallmarks of this cancer entity. On this basis, we discuss new concepts combining distinct treatment modalities in order to improve therapeutic efficacy and clinical outcome – with a specific focus on protocols involving radio(chemo)therapeutic approaches.
Pancreatic ductal adenocarcinomas (PDACs), the most prevalent pancreatic cancer, is highly aggressive with a 5-year overall survival rate of less than 8%. Late detection, it´s metastatic spread and the resistance to chemotherapy are among some of the factors responsible for poor patient outcome. The PDAC incidence rate is increasing and is particularly related to the general aging of our society. Furthermore, life stye habits that include abuse of alcohol and tobacco as well as obesity and type 2 diabetes increases the risk for various types of cancer including PDAC.
Do you need support in meeting your research goals? We can help! We offer custom analytical service measurements for ELISA Kits, Luminex Assays, or microRNA Analysis .
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Custom Analytical Service Measurements for ELISA, Luminex, microRNA
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RELATED PUBLICATIONS
Comprehensive Characterization of Platelet-Enriched MicroRNAs as Biomarkers of Platelet Activation.
Krammer TL, Zeibig S, Schrottmaier WC, Pirabe A, Goebel S, Diendorfer AB, Holthoff HP, Assinger A, Hackl M. Cells. 2022 Apr 7;11(8):1254. doi: 10.3390/cells11081254. PMID: 35455934; PMCID: PMC9030873.
Abstract
Dysregulation of platelet function is causally connected to thrombus formation and cardiovascular diseases. Therefore, assessing platelet reactivity is crucial. However, current platelet function tests come with pitfalls, limiting clinical use. Plasma miRNA signatures have been suggested as novel biomarkers for predicting/diagnosing cardiovascular diseases and monitoring antiplatelet therapy. Here, we provide results from a comprehensive study on the feasibility of using circulatory platelet miRNAs as surrogate markers of platelet activation. We performed small RNA-Seq on different blood cell types to confirm known and identify novel platelet-enriched miRNAs and validated a panel of 16 miRNAs using RT-qPCR. To identify the main carrier of these blood-based platelet miRNAs, we enriched and analyzed distinct microvesicle populations. Platelets were stimulated with GPVI and P2Y12 agonists in vitro to monitor the release of the selected miRNAs following activation. Finally, the miRNA panel was also measured in plasma from mice undergoing the Folts intervention (recurrent thrombus formation in the carotid artery). Applying an unbiased bioinformatics-supported workflow to our NGS data, we were able to confirm a panel of previously established miRNA biomarker candidates and identify three new candidates (i.e., miR-199a-3p, miR-151a-5p, and miR-148b-3p). Basal levels of platelet-derived miRNAs in plasma were mainly complexed with proteins, not extracellular vesicles. We show that changes in miRNA levels due to platelet activation are detectable using RT-qPCR. In addition, we highlight limitations of studying the in vitro release of miRNAs from platelets. In vivo thrombosis resulted in significant elevations of platelet-derived miRNA levels in mice. In conclusion, we provide in-depth evidence that activated platelets release miRNAs, resulting in measurable changes in circulatory miRNA levels, rendering them promising biomarker candidates.
Multiplex Soluble Biomarker Analysis from Pleural Effusion.
Biomolecules. Javadi J, Dobra K, Hjerpe A. 2020 Jul 28;10(8):1113. doi: 10.3390/biom10081113. PMID: 32731396; PMCID: PMC7464384.
Abstract
Malignant pleural mesothelioma (MPM) is a highly aggressive and therapy resistant pleural malignancy that is caused by asbestos exposure. MPM is associated with poor prognosis and a short patient survival. The survival time is strongly influenced by the subtype of the tumor. Dyspnea and accumulation of pleural effusion in the pleural cavity are common symptoms of MPM. The diagnostic distinction from other malignancies and reactive conditions is done using histopathology or cytopathology, always supported by immunohistochemistry, and sometimes also by analyses of soluble biomarkers in effusion supernatant. We evaluated the soluble angiogenesis related molecules as possible prognostic and diagnostic biomarkers for MPM by Luminex multiplex assay. Pleural effusion from 42 patients with malignant pleural mesothelioma (MPM), 36 patients with adenocarcinoma (AD) and 40 benign (BE) effusions were analyzed for 10 different analytes that, in previous studies, were associated with angiogenesis, consisting of Angiopoietin-1, HGF, MMP-7, Osteopontin, TIMP-1, Galectin, Mesothelin, NRG1-b1, Syndecan-1 (SDC-1) and VEGF by a Human Premixed Multi-Analyte Luminex kit. We found that shed SDC-1 and MMP-7 levels were significantly lower, whereas Mesothelin and Galectin-1 levels were significantly higher in malignant mesothelioma effusions, compared to adenocarcinoma. Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1, NRG1-β1, VEGF and TIMP-1 were significantly higher in malignant pleural mesothelioma effusions compared to benign samples. Moreover, there is a negative correlation between Mesothelin and shed SDC-1 and positive correlation between VEGF, Angiopoietin-1 and shed SDC-1 level in the pleural effusion from malignant cases. Shed SDC-1 and VEGF have a prognostic value in malignant mesothelioma patients. Collectively, our data suggest that MMP-7, shed SDC-1, Mesothelin and Galectin-1 can be diagnostic and VEGF and SDC-1 prognostic markers in MPM patients. Additionally, Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1 and TIMP-1 can be diagnostic for malignant cases.
Biomarkers & Bone Health – ELISA Kits for Clinical Research
Bone remodeling is a continuous process that removes bone and replaces it with newly synthesized bone. This bone turnover process preserves the mechanical function of the human skeleton.
Bone turnover biomarkers, e.g. markers of bone formation and bone resorption, have been used during the last decade to monitor bone diseases and to monitor their treatment.
Many of these markers are secreted by osteoblasts and osteoclasts and include regulators of bone turnover e.g. receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG).
Though RANKL and OPG play an integral role in bone turnover, they do not reflect the activity of osteocytes, the most abundant cell type in the bone.
Osteocytes are cells that regulate bone remodeling. They secrete proteins – bone regulation markers – that include Sclerostin (SOST), Dickkopf-1 (DKK-1), and Fibroblast growth factor (FGF23). These markers reflect the osteocyte activity.
The above listed biomarkers circulate and can be measured in serum and plasma allowing the investigation of complex interactions between the bone and their relationship with other organs.
BIOMEDICA ELISA KITS – Biomarkers & Bone Health
check out our Bone Biomarker Brochure
ELISA Assay Kit Highlights
+ EASY – ready to use calibrators & controls included (color-coded reagents)
+FULL VALIDATION PACKAGE – assays are optimized for clinical samples
+ HIGH QUALITY GUARANTEED – results you can rely on
+ WIDELY CITED in 1500 + publications
Biomedica – Complete ready-to-use ELISA kits for superior performance and reproducibility
RELATED PRODUCTS
Osteoprotegerin (OPG) ELISA , soluble RANKL ELISA, Periostin ELISA, DKK-1 ELISA , Sclerostin ELISA
FGF23 ELISA , IL-6 ELISA , VEGF ELISA , Angiopoietin-2 ELISA
osteomiR®– bone miRNA biomarkers highlights:
- Novel minimally invasive biomarkers to detect high imminent fracture-risk in osteoporosis
- 19 individual bone-related biomarkers with distinct information content
RELATED PUBLICATIONS
Novel biological markers of bone: from bone metabolism to bone physiology. Rheumatology (Oxford). Chapurlat RD, Confavreux CB. 2016; 55(10):1714-25.
Abstract
Biochemical markers of bone turnover have been used for decades in the management of bone diseases, to assess the prognosis of these conditions and to monitor treatments. The new markers, however, also reflect specific physiological mechanisms in the bone or other organs. Periostin may be more specific to the periosteum; cathepsin K is an osteoclastic enzyme that may be involved in the cardiovascular system and joints; Dickkopf-1 is involved in bone formation and vascular calcification; sclerostin is a major regulator of bone formation in response to mechanical loading and may also play a role in chronic kidney disease bone and mineral disorder; sphingosine-1-phosphate is a lipid mediator interacting with bone resorption. Some of the bone markers are in fact hormones produced by the bone that affect various physiological and pathological functions in other organs. Thus, osteocalcin is produced by osteoblasts and participates in the regulation of insulin sensitivity and fertility in men. Fibroblast growth factor 23 is produced by osteocytes to regulate phosphorus and 1,25(OH)2D3, but it also plays a major role in the adverse consequences of declining renal function, in particular with respect to the myocardium. Micro RNAs are single-stranded RNAs that regulate several pathways, including the development timing, organogenesis, cell apoptosis, proliferation and differentiation. Their serum concentration may reflect the links between bone physiology and certain conditions in other organs, for example, the cardiovascular system.
Bones have many important biological functions. Bone biomarkers have gained attention in clinical research for the assessment of bone-related diseases. Some of the biomarker proteins have been found to represent useful targets for therapeutic antibodies.
Biomarkers in Bone Biology
Function of the human skeleton
The human skeletal system gives the body it´s structure and helps to protect and support the internal organs. It forms a part of the muscular-skeletal systems that helps the body to move. Throughout our lifetime, the human skeleton undergoes constant remodeling. This dynamic process, degrading bone and replacing it with new tissue maintains bone mass. The continuous cycle of bone resorption and bone growth is also known as bone metabolism.
Bone remodeling
Bone remodeling is a tightly regulated process performed by hormones, cell-signaling molecules, and bone cells. These specific bone cells are osteoclasts, osteoblasts, and osteocytes. The cells are in constant communication with each other through secreted factors, such as osteoprotegerin, RANKL, and sclerostin. These regulatory systems keep the bone remodeling balanced. Imbalances in bone metabolism can lead to bone diseases.
Role of RANKL, RANK, and OPG in bone biology |
Bones are broken down by osteoclasts and rebuilt by osteoblasts.
RANKL receptor activator is a mediator of bone resorption and OPG acts as a decoy receptor.
Osteoprotegerin (OPG) is produced by osteoblasts, cells that synthesize bone. OPG is a decoy receptor and binds to RANKL, antagonizing its binding to RANK.
RANKL (receptor activator of nuclear factor kappa-B ligand) is secreted by osteoblasts and binds to the RANK receptor on osteoclast precursor and mature osteoclast cells. RANKL stimulates bone resorption.
Role of Sclerostin, FGF23, DKK-1, and Periostin in bone biology
Biomarkers in Bone Biology
Bone cells have been reported to have endocrine functions that affect multiple organs. The most abundant cell type in the bone are osteocytes residing within the bone matrix and comprising 90% to 95% of the bone cells. Osteocytes play a significant role in the regulation of osteogenesis, releasing osteocyte-related biomarkers such as sclerostin (SOST), fibroblast growth factor 23 (FGF23), and Dickkopf-1 (DKK-1).
Sclerostin (SOST) is mainly produced by osteocytes and is considered as the major regulator of bone formation. More recently, Sclerostin has been shown to stimulate the osteocyte synthesis of fibroblast growth factor-23, potentially contributing to the regulation of phosphate homeostasis.
Fibroblast growth factor 23 (FGF23) is a hormone that is mainly secreted by osteocytes and osteoblasts. It regulates phosphate and vitamin D levels and functions as a central endocrine hormone regulating phosphate balance.
Dickkopf-1 (DKK-1) is an extracellular protein. DKK-1 plays a role in the regulation of bone metabolism, as it inhibits the differentiation of osteoblasts.
Periostin (POSTN) is an extracellular matrix protein that is preferentially expressed in the periosteum, a membrane covering the outer surface of bones which is responsible for growth. Periostin has functions in osteology, tissue repair, oncology, cardiovascular and respiratory diseases, and in a variety of inflammatory settings (e.g. asthma).
BIOMEDICA OFFERS HIGH QUALITY ELISA KITS FOR BONE BIOMARKERS
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Sclerostin ELISA (cat.no. BI-20492)
OPG ELISA (cat.no. BI-20403)
RANKL ELISA (cat.no. BI-20462)
FGF23 intact ELISA (cat.no. BI-20700)
FGF23 C-terminal ELISA (cat.no. BI-20702)
DKK-1 ELISA (cat.no. BI-20413)
PERIOSTIN ELISA (cat.no. BI-20433)
RELATED LITERATURE
A Review of the Potential Application of Osteocyte-Related Biomarkers, Fibroblast Growth Factor-23, Sclerostin, and Dickkopf-1 in Predicting Osteoporosis and Fractures. Ramli FF, Chin KY. Diagnostics (Basel). 2020 Mar 6;10(3):145. doi: 10.3390/diagnostics10030145. PMID: 32155909; PMCID: PMC7151094.
Sclerostin Directly Stimulates Osteocyte Synthesis of Fibroblast Growth Factor-23. Wijenayaka AR, Yang D, Ormsby RT, Bonewald LF, Atkins GJ. Calcif Tissue Int. 2021 Jul;109(1):66-76. doi: 10.1007/s00223-021-00823-6. Epub 2021 Feb 22. PMID: 33616712.
Biology of the RANKL-RANK-OPG System in Immunity, Bone, and Beyond. Front Immunol. Walsh MC, Choi Y.2014 Oct 20;5:511. doi: 10.3389/fimmu.2014.00511. PMID: 25368616; PMCID: PMC4202272.
The Osteocyte: New Insights. Robling AG, Bonewald LF. Annu Rev Physiol. 2020 Feb 10;82:485-506. doi: 10.1146/annurev-physiol-021119-034332. PMID: 32040934; PMCID: PMC8274561.
Sema4D induces cartilage destruction
Semaphorin 4D destroys cartilage: Semaphorin 4D (Sema 4D) has been identified as an inflammatory cytokine that promotes cartilage destruction. This finding was recently published by Murakami T and colleagues. In a mouse model of inflammatory arthritis, the researchers demonstrated that Sema4D was increased in synovial fluid and loss of Sema4D protected against cartilage degeneration. Click here to learn more.
What is cartilage?
Cartilage is a type of strong and flexible tissue that is found throughout the body. It is a connective tissue that exists in our joints, bones, spine, ears and nose. It protects our joints and our bones, absorbing impact, reducing friction and helping our joints to move smoothly.
If cartilage is degraded, movements will cause friction and pain, leading to swelling and stiffness. Cartilage degradation can be caused through direct injury, osteoarthritis, and aging.
Semaphorin 4D destroys cartilage
Murakami T, Takahata Y, Hata K, Ebina K, Hirose K, Ruengsinpinya L, Nakaminami Y, Etani Y, Kobayashi S, Maruyama T, Nakano H, Kaneko T, Toyosawa S, Asahara H, Nishimura R. Sci Signal. 2022 Nov;15(758):eabl5304. doi: 10.1126/scisignal.abl5304. Epub 2022 Nov 1. PMID: 36318619.
Abstract
Proinflammatory cytokines play critical roles in the pathogenesis of joint diseases. Using a mass spectrometry-based cloning approach, we identified Semaphorin 4D (Sema4D) as an inflammatory cytokine that directly promoted cartilage destruction. Sema4d-deficient mice showed less cartilage destruction than wild-type mice in a model of rheumatoid arthritis. Sema4D induced a proinflammatory response in mouse articular chondrocytes characterized by the induction of proteolytic enzymes that degrade cartilage, such as matrix metalloproteinases (MMPs) and aggrecanases. The activation of Mmp13 and Mmp3 expression in articular chondrocytes by Sema4D did not depend on RhoA, a GTPase that mediates Sema4D-induced cytoskeletal rearrangements. Instead, it required NF-κB signaling and Ras-MEK-Erk1/2 signaling downstream of the receptors Plexin-B2 and c-Met and depended on the transcription factors IκBζ and C/EBPδ. Genetic and pharmacological blockade of these Sema4D signaling pathways inhibited MMP induction in chondrocytes and cartilage destruction in femoral head organ culture. Our results reveal a mechanism by which Sema4D signaling promotes cartilage destruction.
SEMA4D ELISA kit highlights
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RELATED PUBLICATIONS
Inhibition of Semaphorin 4D/Plexin-B1 signaling inhibits the subchondral bone loss in early-stage osteoarthritis of the temporomandibular joint. Zhang Z, Lu L, Ye T, Yu S, Zhang J, Zhang M, He F, Liu Q, Yang H, Feng J.Arch Oral Biol. 2022 Mar;135:105365. doi: 10.1016/j.archoralbio.2022.105365. Epub 2022 Feb 2. PMID: 35151027.
Abstract
Objective: The aim of this study was to demonstrate the biological function of Semaphorin 4D (Sema4D)/Plexin-B1 in the bone formation features of osteoblasts in early-stage temporomandibular joint (TMJ) osteoarthritis.
Design: Sema4D/Plexin-B1, expressed by osteoclasts/osteoblasts, plays a balancing role in bone formation and resorption. However, previous studies have mainly focused on bone resorption by osteoclasts in early-stage osteoarthritis. This study used our reported experimental unilateral anterior crossbite (UAC) mouse model to explore subchondral bone changes, which were assessed by micro-CT analysis. The changes in osteoblasts were investigated after the inhibition of Sema4D by BMA-12 injection with the detection of bone formation-related markers. A Transwell migration assay was performed to reveal the specific impact of Sema4D on osteoblasts in vitro.
Results: The data demonstrated that subchondral bone loss in early-stage TMJ osteoarthritis was accompanied by the upregulated expression of Sema4D in cartilage and subchondral bone and Plexin-B1 in subchondral bone. Reducing Sema4D levels could inhibit subchondral bone loss and cartilage degeneration in early-stage TMJ osteoarthritis. In vitro, the results revealed that Sema4D could reduce the expression of osteocalcin and alkaline phosphatase and increase the migrating capability of Plexin-B1-positive osteoblasts.
Conclusions: Our results revealed that elevated Sema4D expression in early-stage TMJ osteoarthritis might decrease the bone formation activity of osteoblasts in the subchondral bone by binding to Plexin-B1 expressed by osteoblasts. Inhibiting Sema4D/Plexin-B1 signaling in early-stage osteoarthritis represents a promising strategy for new therapeutic approaches to osteoarthritis.
Compliance of NT-proBNP test in accredited cardiac marker survey
NT-proBNP ELISA test successfully passed accredited cardiac marker survey: Biomedica participated in an accredited international ring trial program for the cardiac biomarker NT-proBNP. The results demonstrate that the CE-marked NT-proBNP ELISA assay successfully passed the QC circle in the cardiac marker survey.
NT-proBNP ELISA test successfully passed cardiac marker survey
The results comply with strict quality standards confirmed by RfB, an international provider for proficiency testing.
NT-proBNP ELISA assay kit (cat. no. SK-1204)
√ CE-marked – for IVD use in the EU
√ Flexible – can be run in every lab
√ Two controls included
√ Simple 2 step protocol
√ Reliable – full validation
√ Widely cited in more than 100 publications
Developed & manufactured by Biomedica right in the heart of Europe
What is proficiency testing?
Proficiency Testing provides a report that shows how laboratories can compare their own data to data to data from other laboratories around the world.
The testing, carried out in a ring trial program, is performed by an accredited laboratory specialist in proficiency testing. Proficiency testing monitors the performance of individual laboratories for specific tests e.g. cardiac biomarker assays.
LITERATURE
Monitoring of NT-proBNP – predicting risk of cardiovascular events from anti-inflammatory drugs (Non-Steroid Anti-Inflammatory Drugs)
N-terminal pro-B-type natriuretic peptide concentrations predict the risk of cardiovascular adverse events from antiinflammatory drugs: a pilot trial. Brune K, Katus HA, Moecks J, Spanuth E, Jaffe AS, Giannitsis E. Clin Chem. 2008 Jul;54(7):1149-57. doi: 10.1373/clinchem.2007.097428. Epub 2008 May 1. PMID: 18451314.
Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say? Cooper C, Chapurlat R, Al-Daghri N, Herrero-Beaumont G, Bruyère O, Rannou F, Roth R, Uebelhart D, Reginster JY.Drugs Aging. 2019 Apr;36(Suppl 1):15-24. doi: 10.1007/s40266-019-00660-1. PMID: 31073921; PMCID: PMC6509083.
Cardio-renal safety of non-steroidal anti-inflammatory drugs. Radi ZA, Khan KN. J Toxicol Sci. 2019;44(6):373-391. doi: 10.2131/jts.44.373. PMID: 31168026.
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used therapeutic class in clinical medicine. These are sub-divided based on their selectivity for inhibition of cyclooxygenase (COX) isoforms (COX-1 and COX-2) into: (1) non-selective (ns-NSAIDs), and (2) selective NSAIDs (s-NSAIDs) with preferential inhibition of COX-2 isozyme. The safety and pathophysiology of NSAIDs on the renal and cardiovascular systems have continued to evolve over the years following short- and long-term treatment in both preclinical models and humans. This review summarizes major learnings on cardiac and renal complications associated with pharmaceutical inhibition of COX-1 and COX-2 with focus on preclinical to clinical translatability of cardio-renal data.
Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, Egger M, Jüni P.BMJ. 2011 Jan 11;342:c7086. doi: 10.1136/bmj.c7086. PMID: 21224324; PMCID: PMC3019238.
Pathogenic contribution of LRG1 to vascular retinopathies
Globally, 2.2 billion people are estimated to have a vision impairment. Eye diseases are on the rise due to an ageing population and an increase of diabetes. The classical therapy involves the blockage of vascular endothelial growth factor (VEGF). However, a high rate of patient non-response and loss of efficacy over time are major challenges.
Evaluating new treatments with better efficiency are moving forward. One novel therapeutic target is leucine-rich α-2 glycoprotein 1 (LRG1). It is an emerging key player in vascular dysfunction, inflammation, and fibrosis.
LRG1 as a novel therapeutic target in eye disease
The uncontrolled formation of new blood vessels in the eye (ocular angiogenesis) is one of the major causes of eye diseases and blindness.
The blood protein LRG1 plays a central role in the progression of eye diseases and is thus a promising novel therapeutic target.
In searching for mediators of vascular remodeling in the diseased and damaged retina, researchers discovered that leucine-rich α-2 glycoprotein 1 (LRG1) is a novel regulator of TGFß signaling. The study published in Nature in 2013 by Wang X et al., revealed that LRG1 is a novel regulator of angiogenesis that mediates its effect through modulating TGFβ signaling. The researchers showed that LRG1 expression in the retina is predominantly vascular and is increased during neovascular growth. Their study in mice supported the hypothesis that LRG1 is necessary for robust vascular growth and its inhibition has potential as a therapeutic target. Based on their studies, the authors suggested that LRG1 is not only a promising target for controlling pathogenic angiogenesis in eye diseases but could potentially also be used in other diseases such as cancer and atherosclerosis.
WHAT IS LRG1 (leucine-rich α-2 glycoprotein 1)
The mature 38,2 kDa glyocoprotein LRG contains 347 amino acids (Uniprot entry Leucine-rich alpha-2-glycoprotein). It belongs to the family of LRG proteins characterized through leucine-rich repeats in its amino acid sequence. LRG1 (also named LRG) is involved in protein-protein interactions, signal transduction, and development. Studies have shown that LRG plays a role in physiological processes of the nervous system including synapse formation and growth. It is also implied in cell proliferation, in immune responses, in cell migration, in neovascularization, and in apoptosis.
Alternative titles: LRG – OMIM Entry leucine-rich α-2 glycoprotein (LRG)
HOW CAN YOU MEASURE LRG1?
LRG1 can reliably be measured in human serum and plasma with the Biomedica LRG ELISA (cat. no. BI-LRG).
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Sample volume: 5µl
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Assay range: 2-64 ng/ml
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Easy protocol – day test
The validation of the LRG1 ELISA kit has been performed following international quality guidelines. Download the validation data here.
RELATED PUBLICATIONS
LRG1 as a novel therapeutic target in eye disease.
De Rossi G, Da Vitoria Lobo ME, Greenwood J, Moss SE. Eye (Lond). 2022 Feb;36(2):328-340. doi: 10.1038/s41433-021-01807-4. Epub 2022 Jan 5. Erratum in: Eye (Lond). 2022 Feb 28;: PMID: 34987199; PMCID: PMC8807626.
Abstract
Retinal and choroidal diseases are major causes of blindness and visual impairment in the developed world and on the rise due to an ageing population and diabetes epidemic. Standard of care is centred around blockade of vascular endothelial growth factor (VEGF), but despite having halved the number of patients losing sight, a high rate of patient non-response and loss of efficacy over time are key challenges. Dysregulation of vascular homoeostasis, coupled with fibrosis and inflammation, are major culprits driving sight-threatening eye diseases. Improving our knowledge of these pathological processes should inform the development of new drugs to address the current clinical challenges for patients. Leucine-rich α-2 glycoprotein 1 (LRG1) is an emerging key player in vascular dysfunction, inflammation and fibrosis. Under physiological conditions, LRG1 is constitutively expressed by the liver and granulocytes, but little is known about its normal biological function. In pathological scenarios, such as diabetic retinopathy (DR) and neovascular age-related macular degeneration (nvAMD), its expression is ectopically upregulated and it acquires a much better understood pathogenic role. Context-dependent modulation of the transforming growth-factor β (TGFβ) pathway is one of the main activities of LRG1, but additional roles have recently been emerging. This review aims to highlight the clinical and pre-clinical evidence for the pathogenic contribution of LRG1 to vascular retinopathies, as well as extrapolate from other diseases, functions which may be relevant to eye disease. Finally, we will provide a current update on the development of anti-LRG1 therapies for the treatment of nvAMD..
LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling.
Wang X, Abraham S, McKenzie JAG, Jeffs N, Swire M, Tripathi VB, Luhmann UFO, Lange CAK, Zhai Z, Arthur HM, Bainbridge J, Moss SE, Greenwood J.Nature. 2013 Jul 18;499(7458):306-11. doi: 10.1038/nature12345. PMID: 23868260; PMCID: PMC3836402.
High big ET-1 levels are associated with risk of all–cause death in diabetes patients with CAD
Big Endothelin-1 associated with all-cause death in diabetes patients with CAD
A clinical study in 8550 patients investigated the association between the cardio-vascular marker big endothelin-1 (big ET-1) and long-term all-cause death in patients with coronary artery disease (CAD) and impaired glucose metabolism.
Patients were categorized into both glucose status (diabetes mellitus, pre-diabetes mellitus, normalglycemia) and big ET-1 level groups. Primary endpoint was all-cause death. The data indicate that baseline big ET-1 levels were independently associated with the long-term mortality in diabetes patients with CAD.
Read more Big Endothelin-1 associated with all-cause death in diabetes patients with CAD.
What is Big Endothelin-1 (Big ET-1) ?
Big ET-1 is a 38 amino acid peptide and is the precursor of Endothelin-1 (ET-1). ET-1 is a potent vasoconstrictor secreted by endothelial cells. It acts as the counterpart of the vasodilator nitric oxide (NO).
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ET-1 is cleaved from Big ET-1 by the ET converting enzyme -1 (ECE-1).
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Both the precursor Big ET-1 and the shorter 21 aminoacid vasoactive form Endothelin-1 circulate in blood.
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ET-1, the biologically active form, is rapidly cleared and has a short half-life.
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ET-1 and big ET-1 are found in equimolar concentrations in the plasma.
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Thus, the longer half-life of big ET-1, its slower clearance and the findings that increased plasma levels of ET-1 in patients with heart failure are mainly due to an increase in big ET-1 concentrations, offers an analytical window for the measurement of Big ET-1 .
How can you measure Big ET-1?
Big ET-1 can easily be measured using in serum and plasma with only 50µl sample volume.
Biomedica’s Big ET-1 ELISA cat. no. BI-20082H
√ Direct measurement – highly sensitive
√ Full validation package
√ Widely cited +75 publications
check out the customer review on Biocompare
Related publications – Citations Big ET-1 ELISA – Biomedica
The Biomedica Big Endothelin-1 (Big ET-1) ELISA kit was utilized in the following studies:
Xu N, Zhu P, Yao Y, Jiang L, Jia S, Yuan D, Xu J, Wang H, Song Y, Gao L, Gao Z, Song L, Zhao X, Chen J, Yang Y, Xu B, Gao R, Yuan J. Nutr Metab Cardiovasc Dis. 2022 Sep;32(9):2147-2156. doi: 10.1016/j.numecd.2022.06.002. Epub 2022 Jun 11. PMID: 35843800.
Abstract
Background and aims: The present study aimed to examine the association between big endothelin-1 (big ET-1) and long-term all-cause death in patients with coronary artery disease (CAD) and different glucose metabolism status.
Methods and results: We consecutively enrolled 8550 patients from January 2013 to December 2013. Patients were categorized according to both status of glucose metabolism status [Diabetes Mellitus (DM), Pre-Diabetes (Pre-DM), Normoglycemia (NG)] and big ET-1 levels. Primary endpoint was all-cause death. During a median of 5.1-year follow-up periods, 301 all-cause deaths occurred. Elevated big ET-1 was significantly associated with long-term all-cause death (adjusted HR: 2.230, 95%CI 1.629-3.051; p < 0.001). Similarly, patients with DM, but not Pre-DM, had increased risk of all-cause death compared with NG group (p < 0.05). When patients were categorized by both status of glucose metabolism and big ET-1 levels, high big ET-1 were associated with significantly higher risk of all-cause death in Pre-DM (adjusted HR: 2.442, 95% CI 1.039-5.740; p = 0.041) and DM (adjusted HR: 3.162, 95% CI 1.376-7.269; p = 0.007). The Kaplan-Meier curve indicated that DM patients with the highest big ET-1 levels were associated with the greatest risk of all-cause death (p < 0.05).
Conclusions: The present data indicate that baseline big ET-1 levels were independently associated with the long-term all-cause death in DM and Pre-DM patients with CAD undergoing PCI, suggesting that big ET-1 may be a valuable marker in patients with impaired glucose metabolism.
Predictive Value of Plasma Big Endothelin-1 in Adverse Events of Patients With Coronary Artery Restenosis and Diabetes Mellitus: Beyond Traditional and Angiographic Risk Factors. Ma Y, Tian T, Wang T, Wang J, Guan H, Yuan J, Song L, Yang W, Qiao S. Front Cardiovasc Med. 2022 May 26;9:854107. doi: 10.3389/fcvm.2022.854107. PMID: 35694656; PMCID: PMC9177997.
Big Endothelin-1 and long-term all-cause death in patients with coronary artery disease and prediabetes or diabetes after percutaneous coronary intervention . Xu N, Zhu P, Yao Y, Jiang L, Jia S, Yuan D, Xu J, Wang H, Song Y, Gao L, Gao Z, Song L, Zhao X, Chen J, Yang Y, Xu B, Gao R, Yuan J. Nutr Metab Cardiovasc Dis. 2022 Sep;32(9):2147-2156. doi: 10.1016/j.numecd.2022.06.002. Epub 2022 Jun 11. PMID: 35843800.
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, Sancho-Tello MJ, Martínez-Dolz L, Sevilla B, Taléns-Visconti R, Jordán A, Miró V, Pérez-Boscá JL, Marín F, Climent V, García de Burgos F, Payá R, Sogorb F, Bertomeu V, Salvador A. Rev Esp Cardiol. 2005 Mar;58(3):278-84. Spanish. PMID: 15766450.
Plasma big endothelin-1 concentrations in congestive heart failure patients with or without systemic hypertension. Pacher R, Bergler-Klein J, Globits S, Teufelsbauer H, Schuller M, Krauter A, Ogris E, Rödler S, Wutte M, Hartter E. Am J Cardiol. 1993 Jun 1;71(15):1293-9. doi: 10.1016/0002-9149(93)90543-l. PMID: 8498369.
Plasma big endothelin-1 levels at admission and future cardiovascular outcomes: A cohort study in patients with stable coronary artery disease. Zhou BY, Guo YL, Wu NQ, Zhu CG, Gao Y, Qing P, Li XL, Wang Y, Dong Q, Liu G, Xu RX, Cui CJ, Sun J, Li JJ. Int J Cardiol. 2017 Mar 1;230:76-79. doi: 10.1016/j.ijcard.2016.12.082. Epub 2016 Dec 21. PMID: 28038820.
Background: Big endothelin-1 (ET-1) has been proposed as a novel prognostic indicator of acute coronary syndrome, while its predicting role of cardiovascular outcomes in patients with stable coronary artery disease (CAD) is unclear.
Methods and results: A total of 3154 consecutive patients with stable CAD were enrolled and followed up for 24months. The outcomes included all-cause death, non-fatal myocardial infarction, stroke and unplanned revascularization (percutaneous coronary intervention and coronary artery bypass grafting). Baseline big ET-1 was measured using sandwich enzyme immunoassay method. Cox proportional hazard regression analysis and Kaplan-Meier analysis were used to evaluate the prognostic value of big ET-1 on cardiovascular outcomes. One hundred and eighty-nine (5.99%) events occurred during follow-up. Patients were divided into two groups: events group (n=189) and non-events group (n=2965). The results indicated that the events group had higher levels of big ET-1 compared to non-events group. Multivariable Cox proportional hazard regression analysis showed that big ET-1 was positively and statistically correlated with clinical outcomes (Hazard Ratio: 1.656, 95% confidence interval: 1.099-2.496, p=0.016). Additionally, the Kaplan-Meier analysis revealed that patients with higher big ET-1 presented lower event-free survival (p=0.016).
Conclusions: The present study firstly suggests that big ET-1 is an independent risk marker of cardiovascular outcomes in patients with stable CAD. And more studies are needed to confirm our findings.
Superiority of big endothelin-1 and endothelin-1 over natriuretic peptides in predicting survival in severe congestive heart failure: a 7-year follow-up study. Van Beneden R, Gurné O, Selvais PL, Ahn SA, Robert AR, Ketelslegers JM, Pouleur HG, Rousseau MF. J Card Fail. 2004 Dec;10(6):490-5. doi: 10.1016/j.cardfail.2004.04.001. PMID: 15599839.
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Full validation package- assays are optimized for clinical samples
developed & manufactured by Biomedica. Austrian Quality.
IL-6 (Interleukin-6) high sensitivity
VEGF low sample volume – 10µl
ANGIOPOIETIN-2 optimized assay range
All kits include color coded, ready to use prediluted standards and controls.
Citations
Ana-Maria Suciu Andreea, Jacqueline Wallwitz, Berg Gabriela, Maria Laber Anna, Himmler Gottfried. Nephrology Dialysis Transplantation, Volume 34, Issue Supplement_1, June 2019, gfz103.SP339, https://doi.org/10.1093/ndt/gfz103.SP339
Click here to view poster: ERA-EDTA Poster 2019 Human Angiopoietin-2
Abstract
INTRODUCTION: Angiopoietin-2 (Ang-2) is an important regulator of the angiopoietin-1/Tie-2 receptor signaling system on endothelial cells during angiogenesis. Disruption of this signaling leads to the loss of endothelial integrity and renders the endothelium response towards a variety of pro-inflammatory cytokines and growth factors. Thus, Ang-2 might lead to vascular micro-inflammation in patients with CKD (chronic kidney disease). Ang-2 levels increase with CKD stage, are associated with fluid overload and abnormal cardiac structure and predict mortality in patients with CKD stages 4–5. Although Ang-2 levels return toward normal after successful kidney transplantation, Ang-2 remains a putative cardiovascular risk factor in this population.
METHODS: An enzyme-linked immunosorbent assay for the detection of all three angiopoietin-2 isoforms in human serum and plasma was developed. Two high quality antibodies are combined in a sandwich test format: As capturing antibody a recombinant monoclonal antibody is used. A biotin-labeled polyclonal affinity-purified antibody serves for detection of the analyte. High resolution epitope mapping of the antibodies via peptide microarray technology allowed the identification of linear antibody epitopes. Technical performance and accuracy of the assay were assessed according to ICH/EMEA guidelines.
RESULTS: Microarray data illustrate the binding of the polyclonal detection antibody to human angiopoietin-2 spotted on a chip. Altogether, seven linear epitopes located N-terminal/at the center of angiopoietin-2 were detected. Most relevant linear epitopes are epitope e2 in the super clustering region and e6 near the fibrinogen-like domain, displaying a twofold higher fluorescent signal than the remaining epitopes. For the recombinant monoclonal antibody no fluorescence was recorded. This antibody recognizes a structural epitope within the C-terminus of angiopoietin-2, which covers the bioactive receptor-binding site of the protein. We expect to detect all described angiopoietin-2 isoforms, as the receptor-binding site is conserved and the majority of the polyclonal antibody epitopes are present in all isoforms. This assay is in conformance with ICH/EMEA/FDA guidelines. Validation data demonstrate its applicability in nephrological disorders including chronic kidney disease. Here we compare an apparently healthy population to chronic kidney disease samples on haemodialysis and kidney transplant samples.
CONCLUSIONS: This new angiopoietin-2 ELISA enables a quick and accurate quantification of all human angiopoietin-2 isoforms that are bioactive in chronic kidney disease and other nephrological disorders.
RELATED LITERATURE
- Molnar et al. (2014): Circulating angiopoietin-2 levels predict mortality in kidney transplant recipients: a 4-year prospective case–cohort study. Transplant International, 27 (6): 541-52. 2. David et al. (2010): Circulating angiopoietin-2 levels increase with progress of chronic kidney disease. Nephrol. Dial. Transplant, 25: 2571-2579,
- Tsai et al. (2017): The interaction between fluid status and angiopoietin-2 in adverse renal outcomes of chronic kidney disease. PLoS One, 12 (3): e173906.
- Tsai et al. (2016): Angiopoietin-2, Angiopoietin-1 and subclinical cardiovascular disease in Chronic Kidney Disease. Scientific Reports, 6:39400
Circulating DKK-1 levels predict disease outcomes and mirror metabolic adaptations in patients with Covid-19
Individuals with low serum levels of DKK1 (Dickkopf-1) are twice as likely to die from Covid-19 than those with high levels according to new research published by Nikolai Jaschke and colleagues in the Journal of Clinical Endocrinology & Metabolism.
The researchers found that circulating DKK1 levels vary in humans and change as a function of time during SARS-CoV-2 infection. The infection promotes metabolic adaptations that resembles fasting, which are mirrored by circulating DKK1 levels. DKK-1 levels predict disease outcomes in Covid-19 individuals.
The results of the study suggest a potential clinical use of measuring circulating DKK1 as an indicator of disease severity in COVID-19 patients.
Circulating DKK1 levels were measured with the DKK-1 ELISA kit from Biomedica
Biomedica, Vienna, Austria, DKK-1 ELISA, catalog #BI-20413, RRID: AB_2922680
Highlights – DKK-1 ELISA (cat. no. BI-20413)
- Small sample volume – 20µl serum/well
- Reliable –international validation guidelines
- Easy – direct measurement
- Widely cited in +170 publications
Circulating Dickkopf1 parallels metabolic adaptations and predicts disease trajectories in patients with Covid-19. Full text link
Jaschke NP, Funk AM, Jonas S, Riffel RM, Sinha A, Wang A, Pählig S, Hofmann M, Altmann H, Von Bonin S, Koch T, Spieth P, Tausche K, Akgün K, Rauner M, Kronstein-Wiedemann R, Odendahl M, Tonn T, Göbel A, Hofbauer LC, Rachner TD. J Clin Endocrinol Metab. 2022 Sep 8:dgac514. doi: 10.1210/clinem/dgac514. Epub ahead of print. PMID: 36071553; PMCID: PMC9494396.
Abstract
Context and aims: Coronavirus disease 19 (COVID-19) trajectories show high interindividual variability, ranging from asymptomatic manifestations to fatal outcomes, the latter of which may be fueled by immunometabolic maladaptation of the host. Reliable identification of patients who are at risk of severe disease remains challenging. We hypothesized that serum concentrations of Dickkopf1 (DKK1) indicate disease outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals.
Methods: We recruited hospitalized patients with PCR-confirmed SARS-CoV-2 infection and included 80 individuals for whom blood samples from 2 independent time points were available. DKK1 serum concentrations were measured by ELISA in paired samples. Clinical data were extracted from patient charts and correlated with DKK1 levels. Publicly available datasets were screened for changes in cellular DKK1 expression on SARS-CoV-2 infection. Plasma metabolites were profiled by nuclear magnetic resonance spectroscopy in an unbiased fashion and correlated with DKK1 data. Kaplan-Meier and Cox regression analysis were used to investigate the prognostic value of DKK1 levels in the context of COVID-19.
Results: We report that serum levels of DKK1 predict disease outcomes in patients with COVID-19. Circulating DKK1 concentrations are characterized by high interindividual variability and change as a function of time during SARS-CoV-2 infection, which is linked to platelet counts. We further find that the metabolic signature associated with SARS-CoV-2 infection resembles fasting metabolism and is mirrored by circulating DKK1 abundance. Patients with low DKK1 levels are twice as likely to die from COVID-19 than those with high levels, and DKK1 predicts mortality independent of markers of inflammation, renal function, and platelet numbers.
Conclusion: Our study suggests a potential clinical use of circulating DKK1 as a predictor of disease outcomes in patients with COVID-19. These results require validation in additional cohorts.
Decrease of bone biomarker Sclerostin in women with anorexia nervosa during nutrition therapy – indication of reduced bone loss
Anorexia nervosa (AN) is an eating disorder and has one of the highest mortality rates of any mental illness. It affects roughly 2.9 million people and many experience bone loss and increased fracture risk. In a 3-year prospective study, Swedish researchers looked into the long-term effects of nutrition therapy. They investigated bone and mineral metabolism and biomarkers young women with AN. Their results showed that body mass index (BMI) and fat mass was increased. The regulatory bone biomarker Sclerostin decreased during nutrition therapy and further over 3 years, indicating reduced bone loss.
Read more: Bone mass and biomarkers in young women with anorexia nervosa: a prospective 3-year follow-up study.
Biomedica Sclerostin ELISA kit
- The internationally most referenced Sclerostin ELISA with more than 270 citations!
- Rigorously validated according to international quality guidelines
- Low sample volume
Bone mass and biomarkers in young women with anorexia nervosa: a prospective 3-year follow-up study.
Svedlund A, Pettersson C, Tubic B, Ellegård L, Elfvin A, Magnusson P, Swolin-Eide D. J Bone Miner Metab. 2022 Aug 12. doi: 10.1007/s00774-022-01359-x. Epub ahead of print. PMID: 35960382.
Abstract
Introduction: Anorexia nervosa (AN) increases the risk of impaired bone health, low areal bone mineral density (aBMD), and subsequent fractures. This prospective study investigated the long-term effects of bone and mineral metabolism on bone and biomarkers in 22 women with AN.
Materials and methods: Body composition and aBMD were measured by dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography. Total and free 25-hydroxyvitamin D (25OHD), C-terminal collagen cross-links (CTX), osteocalcin, bone-specific alkaline phosphatase (BALP), leptin, sclerostin, and oxidized/non-oxidized parathyroid hormone (PTH) were analyzed before and after 12 weeks of intensive nutrition therapy and again 3 years later. An age-matched comparison group of 17 healthy women was recruited for the 3-year follow-up.
Results: Body mass index (BMI) and fat mass increased from baseline to 3 years in women with AN. Sclerostin decreased during nutrition therapy and further over 3 years, indicating reduced bone loss. CTX was elevated at baseline and after 12 weeks but decreased over 3 years. BALP increased during nutrition therapy and stabilized over 3 years. Free 25OHD was stable during treatment but decreased over 3 years. Non-oxidized PTH was stable during treatment but increased over 3 years. Trabecular volumetric BMD in AN patients decreased during the first 12 weeks and over 3 years despite stable BMI and bone biomarkers implying increased BMD.
Conclusion: Our findings highlight the importance of early detection and organized long-term follow-up of bone health in young women with a history of AN.
Keywords: DXA; Eating disorder; Osteoporosis; Sclerostin; Vitamin D
Related publications
Anorexia nervosa: 30-year outcome.
Dobrescu SR, Dinkler L, Gillberg C, Råstam M, Gillberg C, Wentz E. Br J Psychiatry. 2020 Feb;216(2):97-104. doi: 10.1192/bjp.2019.113. PMID: 31113504; PMCID: PMC7557598.
Abstract
Background: Little is known about the long-term outcome of anorexia nervosa.
Aims: To study the 30-year outcome of adolescent-onset anorexia nervosa.
Method: All 4291 individuals born in 1970 and attending eighth grade in 1985 in Gothenburg, Sweden were screened for anorexia nervosa. A total of 24 individuals (age cohort for anorexia nervosa) were pooled with 27 individuals with anorexia nervosa (identified through community screening) who were born in 1969 and 1971-1974. The 51 individuals with anorexia nervosa and 51 school- and gender-matched controls were followed prospectively and examined at mean ages of 16, 21, 24, 32 and 44. Psychiatric disorders, health-related quality of life and general outcome were assessed.
Results: At the 30-year follow-up 96% of participants agreed to participate. There was no mortality. Of the participants, 19% had an eating disorder diagnosis (6% anorexia nervosa, 2% binge-eating disorder, 11% other specified feeding or eating disorder); 38% had other psychiatric diagnoses; and 64% had full eating disorder symptom recovery, i.e. free of all eating disorder criteria for 6 consecutive months. During the elapsed 30 years, participants had an eating disorder for 10 years, on average, and 23% did not receive psychiatric treatment. Good outcome was predicted by later age at onset among individuals with adolescent-onset anorexia nervosa and premorbid perfectionism.
Conclusions: This long-term follow-up study reflects the course of adolescent-onset anorexia nervosa and has shown a favourable outcome regarding mortality and full symptom recovery. However, one in five had a chronic eating disorder.
Mitchell JE, Peterson CB. N Engl J Med. 2020 Apr 2;382(14):1343-1351. doi: 10.1056/NEJMcp1803175. PMID: 32242359.
Osteoporosis Awareness –
Worldwide around 200 million women have osteoporosis. Osteoporosis is a disease that weakens bone. Bones become fragile and porous. From the outside, the osteoporotic bone is shaped like normal bone. However, the inside of the bone loses density and becomes weak. The risk of fractures become greater with age, due to the loss of minerals like calcium and phosphate. Osteoporosis most often affects bones in the hip, the spine and the wrist. Factors that influence bone health are nutrition, exercise and hormonal factors. Osteoporosis cannot be cured but delayed through early intervention and biomarker research has identified proteins that may help to identify patients at risk.
BIOMEDICA offers ELISA kits to measure Bone Biomarkers in human serum or plasma samples:
Osteoprotegerin (OPG) ELISA , DKK-1 ELISA , Sclerostin ELISA , soluble RANKL ELISA and others…
IL-6 ELISA , VEGF ELISA , Angiopoietin-2 ELISA
How can you prevent Osteoporosis?
Osteoporosis prevention includes a balanced diet, containing sufficient amounts of calcium and vitamin D and regular exercise.
Exercises to protect or reduce your chance of fracture include regular weight-bearing exercise (eg. weight lifting or resistance training) or any kind of activity that carries your own body weight (e.g. walking, running, climbing stairs, dancing).
A healthy and balanced diet with the recommended daily amounts of calcium are important for bone health. Read more about “Good for your bone foods .
Related literature
The Effectiveness of Physical Exercise on Bone Density in Osteoporotic Patients.
Benedetti MG, Furlini G, Zati A, Letizia Mauro G. Biomed Res Int. 2018. 23;2018:4840531. PMID: 30671455. Link to full text
Abstract
Physical exercise is considered an effective means to stimulate bone osteogenesis in osteoporotic patients. The authors reviewed the current literature to define the most appropriate features of exercise for increasing bone density in osteoporotic patients. Two types emerged: (1) weight-bearing aerobic exercises, i.e., walking, stair climbing, jogging, and Tai Chi. Walking alone did not appear to improve bone mass; however it is able to limit its progressive loss. In fact, in order for the weight-bearing exercises to be effective, they must reach the mechanical intensity useful to determine an important ground reaction force. (2) Strength and resistance exercises: these are carried out with loading (lifting weights) or without (swimming, cycling). For this type of exercise to be effective a joint reaction force superior to common daily activity with sensitive muscle strengthening must be determined. These exercises appear extremely site-specific, able to increase muscle mass and BMD only in the stimulated body regions. Other suggested protocols are multicomponent exercises and whole body vibration. Multicomponent exercises consist of a combination of different methods (aerobics, strengthening, progressive resistance, balancing, and dancing) aimed at increasing or preserving bone mass. These exercises seem particularly indicated in deteriorating elderly patients, often not able to perform exercises of pure reinforcement. However, for these protocols to be effective they must always contain a proportion of strengthening and resistance exercises. Given the variability of the protocols and outcome measures, the results of these methods are difficult to quantify. Training with whole body vibration (WBV): these exercises are performed with dedicated devices, and while it seems they have effect on enhancing muscle strength, controversial findings on improvement of BMD were reported. WBV seems to provide good results, especially in improving balance and reducing the risk of falling; in this, WBV appears more efficient than simply walking. Nevertheless, contraindications typical of senility should be taken into account.
Exercise for the prevention of osteoporosis in postmenopausal women: an evidence-based guide to the optimal prescription.
Daly RM, Dalla Via J, Duckham RL, Fraser SF, Helge EW.Braz J Phys Ther. 2019.23(2):170-180. PMID: 30503353. Full text link
Abstract
Background: Osteoporosis and related fragility fractures are a global public health problem in which pharmaceutical agents targeting bone mineral density (BMD) are the first line of treatment. However, pharmaceuticals have no effect on improving other key fracture risk factors, including low muscle strength, power and functional capacity, all of which are associated with an increased risk for falls and fracture, independent of BMD. Targeted exercise training is the only strategy that can simultaneously improve multiple skeletal and fall-related risk factors, but it must be appropriately prescribed and tailored to the desired outcome(s) and the specified target group.
Objectives: In this review, we provide an overview of the general principles of training and specific loading characteristics underlying current exercise guidelines for the prevention of osteoporosis, and an update on the latest scientific evidence with regard to the type and dose of exercise shown to positively influence bone mass, structure and strength and reduce fracture risk in postmenopausal women.