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Journal of the American Heart... Oct 2019Background It is recognized that factors beyond aortic size are important in predicting outcome in abdominal aortic aneurysm (AAA) disease. AAA is characterized by the... (Observational Study)
Observational Study
Background It is recognized that factors beyond aortic size are important in predicting outcome in abdominal aortic aneurysm (AAA) disease. AAA is characterized by the breakdown of elastin within the aortic tunica media, leading to aortic dilatation and rupture. The aim of this study was to investigate the association of plasma desmosine (pDES), an elastin-specific degradation product, with disease severity and clinical outcome in patients with AAA. Methods and Results We measured pDES and serum biomarker concentrations in 507 patients with AAAs (94% men; mean age, 72.4±6.1 years; mean AAA diameter, 48±8 mm) and 162 control subjects (100% men; mean age, 71.5±4.4 years) from 2 observational cohort studies. In the longitudinal cohort study (n=239), we explored the incremental prognostic value of pDES on AAA events. pDES was higher in patients with AAA compared with control subjects (mean±SD: 0.46±0.22 versus 0.33±0.16 ng/mL; <0.001) and had the strongest correlation with AAA diameter (=0.39; <0.0001) of any serum biomarker. After adjustment for baseline AAA diameter, pDES was associated with an AAA event (hazard ratio, 2.03 per SD increase [95% CI, 1.02-4.02]; =0.044). In addition to AAA diameter, pDES provided incremental improvement in risk stratification (continuous net reclassification improvement, 34.4% [95% CI, -10.8% to 57.5%; =0.09]; integrated discrimination improvement, 0.04 [95% CI, 0.00-0.15; =0.050]). Conclusions pDES concentrations predict disease severity and clinical outcomes in patients with AAA. Clinical Trial Registration http://www.isrctn.com. Unique identifier: ISRCTN76413758.
Topics: Aged; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Biomarkers; Cardiac Catheterization; Desmosine; Female; Follow-Up Studies; Humans; Incidence; Male; Prognosis; Prospective Studies; Survival Rate; Ultrasonography; United Kingdom
PubMed: 31595818
DOI: 10.1161/JAHA.119.013743 -
High value applications and current commercial market for eggshell membranes and derived bioactives.Food Chemistry Jul 2022Chicken eggshell membrane (ESM) is a highly insoluble structure that is greatly stabilized by extensive desmosine, isodesmosine, and disulfide cross-linkages. The ESM... (Review)
Review
Chicken eggshell membrane (ESM) is a highly insoluble structure that is greatly stabilized by extensive desmosine, isodesmosine, and disulfide cross-linkages. The ESM possesses numerous biological functions including anti-microbial, anti-inflammatory, anti-wrinkle, and antioxidant activities. The ESM is mainly proteinaceous; proteomics and bioinformatics analysis of ESM has identified > 500 proteins, such as collagens, glycoproteins, avian beta-defensins, and lysozyme. ESM also contains significant amounts of carbohydrate, including hyaluronic acid (HA). In general, HA plays an important role in tissue hydration and cellular mechanisms such as growth, differentiation, and transport, and has diverse health and medical applications. Despite ESM being rich in important bioactive compounds, it is often considered as a waste product of the egg-breaking industry and is under-utilized. A major challenge for the successful commercial exploitation of ESM and bioactive constituents is its limited solubility and bioavailability due to cross-linkages of ESM fibers. Various processing and extraction methods are employed to overcome these limitations and improve the production of HA and collagen-based ESM formats. Moreover, we believe that there is a wide scope to exploit ESM for novel applications, leading to new intellectual property (IP) and patenting opportunities. This review presents an overview of scientific background, IP landscape and current commercial market for ESM and derived bioactives including collagens and HA. A detailed literature survey is provided for each area of interest. We analyze regulatory guidelines for ESM, contrasting quality control / microbial safety assessment in cosmetics and personal care products (hazard based) with that of the food industry (risk-based). New perspectives for upcycling of ESM waste to commercially viable high-value biomaterials as nutraceutical supplements and as cosmetics ingredients are discussed. This overview of ESM separation techniques and applications could form the basis for directed research and product development in order to exploit the unique bioactivities of ESM.
Topics: Animals; Biocompatible Materials; Chickens; Collagen; Egg Shell; Proteomics
PubMed: 35149473
DOI: 10.1016/j.foodchem.2022.132270 -
PloS One 2023Acute lung injury (ALI) is a life-threatening disease that has received considerable critical attention in the field of intensive care. This study aimed to explore the...
Acute lung injury (ALI) is a life-threatening disease that has received considerable critical attention in the field of intensive care. This study aimed to explore the role and mechanism of vitamin K2 (VK2) in ALI. Intraperitoneal injection of 7 mg/kg LPS was used to induce ALI in mice, and VK2 injection was intragastrically administered with the dose of 0.2 and 15 mg/kg. We found that VK2 improved the pulmonary pathology, reduced myeloperoxidase (MPO) activity and levels of TNF-α and IL-6, and boosted the level of IL-10 of mice with ALI. Moreover, VK2 played a significant part in apoptosis by downregulating and upregulating Caspase-3 and Bcl-2 expressions, respectively. As for further mechanism exploration, we found that VK2 inhibited P38 MAPK signaling. Our results also showed that VK2 inhibited ferroptosis, which manifested by reducing malondialdehyde (MDA) and iron levels, increasing glutathione (GSH) level, and upregulated and downregulated glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HO-1) expressions, respectively. In addition, VK2 also inhibited elastin degradation by reducing levels of uncarboxylated matrix Gla protein (uc-MGP) and desmosine (DES). Overall, VK2 robustly alleviated ALI by inhibiting LPS-induced inflammation, apoptosis, ferroptosis, and elastin degradation, making it a potential novel therapeutic candidate for ALI.
Topics: Mice; Animals; Ferroptosis; Lipopolysaccharides; Vitamin K 2; Elastin; Acute Lung Injury; Inflammation; Apoptosis; Lung
PubMed: 38011192
DOI: 10.1371/journal.pone.0294763 -
Analytical and Bioanalytical Chemistry Oct 2018Desmosine (Des) and isodesmosine (Isodes), cross-linking amino acids in the biomolecule elastin, may be used as biomarkers for various pathological conditions associated...
Desmosine (Des) and isodesmosine (Isodes), cross-linking amino acids in the biomolecule elastin, may be used as biomarkers for various pathological conditions associated with elastin degradation. The current study presents a novel approach to quantify Des and Isodes using matrix-assisted laser desorption ionization (MALDI)-tandem mass spectrometry (MS) in a linear ion trap coupled to a vacuum MALDI source. MALDI-MS analyses of Des and Isodes are performed using stable-isotope-labeled desmosine d (labeled-Des) as an internal standard in different biological fluids, such as urine and serum. The method demonstrated linearity over two orders of magnitude with a detection limit of 0.02 ng/μL in both urine and serum without enrichment prior to mass spectrometry, and relative standard deviation of < 5%. The method is used to evaluate the time-dependent degradation of Des upon UV irradiation (254 nm) and found to be consistent with quantification by H NMR. This is the first characterized MALDI-MS method for quantification of Des and Isodes and illustrates the potential of MALDI-ion trap MS for effective quantification of biomolecules. The reported method represents improvement over current liquid chromatography-based methods with respect to analysis time and solvent consumption, while maintaining similar analytical characteristics. Graphical abstract ᅟ.
Topics: Desmosine; Humans; Limit of Detection; Reference Standards; Reproducibility of Results; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tandem Mass Spectrometry
PubMed: 30062515
DOI: 10.1007/s00216-018-1288-z -
Biomarkers : Biochemical Indicators of... Jun 2022Desmosine and isodesmosine (DID) are biomarkers for elastic fibre damage in pulmonary emphysema. However, current methods for measuring lung DID involve tissue...
INTRODUCTION
Desmosine and isodesmosine (DID) are biomarkers for elastic fibre damage in pulmonary emphysema. However, current methods for measuring lung DID involve tissue hydrolysis and lack specificity for those fibres undergoing breakdown. To address this limitation, free (nonpeptide-bound) DID content in unhydrolyzed tissues was evaluated as a more accurate biomarker in an animal model of pulmonary emphysema.
METHODS
Hamsters were treated with either cigarette smoke and lipopolysaccharide (LPS), room air and LPS, or room air alone (controls). Free DID levels in fresh and formalin-fixed lungs were measured by LC-MS/MS and correlated with the mean linear intercept (MLI) measure of airspace size.
RESULTS
There was no significant difference in free DID between fresh and formalin-fixed lungs. Animals treated with smoke and LPS had significantly higher levels of free DID than the LPS only group (359 vs. 93.1 ng/g wet lung, respectively; = 0.0012) and room air controls (undetectable levels; = 0.0002). There was a significant positive correlation between free DID and MLI ( < 0.0001).
CONCLUSIONS
The results support the hypothesis that free lung DID is a sensitive indicator of alveolar wall injury that may be used to study the development of pulmonary emphysema in both animal models and post-mortem human lung tissue.
Topics: Animals; Biomarkers; Bronchoalveolar Lavage Fluid; Chromatography, Liquid; Cricetinae; Desmosine; Elastic Tissue; Formaldehyde; Humans; Isodesmosine; Lipopolysaccharides; Lung; Pulmonary Emphysema; Tandem Mass Spectrometry
PubMed: 35170389
DOI: 10.1080/1354750X.2022.2043443 -
Respiratory Research Mar 2018Although chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) seem to be opposite entities from a clinical perspective, common initial...
Although chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) seem to be opposite entities from a clinical perspective, common initial pathogenic steps have been suggested in both lung diseases. Emphysema is caused by an elastase/anti-elastase imbalance leading to accelerated elastin degradation. Elastinolysis is however, also accelerated in the IPF patients' lungs. The amino acids desmosine and isodesmosine (DES) are unique to elastin. During the degradation process, elastases liberate DES from elastin fibers. Blood DES levels consequently reflect the rate of systemic elastinolysis and are increased in COPD. This is the first report describing elevated DES levels in IPF patients. We also demonstrated that the age-related increment of DES concentrations is enhanced in IPF. Our current study suggests that elastinolysis is a shared pathogenic step in both COPD and IPF. Further investigation is required to establish the relevance of accelerated elastin degradation in IPF and to determine whether decelerating this process leads to slower progression of lung fibrosis and better survival for patients with IPF.
Topics: Aged; Aging; Biomarkers; Desmosine; Elastin; Female; Humans; Idiopathic Pulmonary Fibrosis; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive
PubMed: 29558926
DOI: 10.1186/s12931-018-0747-6 -
Chest Apr 2018Insights into the clinical course of COPD indicate the need for new therapies for this condition. The discovery of alpha-1 antitrypsin deficiency (AATD) led to the...
Insights into the clinical course of COPD indicate the need for new therapies for this condition. The discovery of alpha-1 antitrypsin deficiency (AATD) led to the protease-antiprotease imbalance hypothesis, which was applied to COPD related to AATD as well as COPD not related to AATD. The discovery of AATD brought recognition to the importance of elastin fibers in maintaining lung matrix structure. Two cross-linking amino acids, desmosine and isodesmosine (DI), are unique to mature elastin and can serve as biomarkers of the degradation of elastin. The intravenous augmentation treatment and lung density in severe alpha-1 antitrypsin deficiency (RAPID) study shows a correlation of an anatomic index of COPD (on CT imaging) correlating with a chemical indicator of matrix injury in COPD, DI. The results suggest that preservation of lung elastin structure may slow the progression of COPD. Hyaluronan aerosol decreases the severity of elastase-induced emphysema in animals and has induced reductions in DI levels in preliminary human studies. Hyaluronan deserves further development as a therapy for COPD.
Topics: Adjuvants, Immunologic; Animals; Biomarkers; Clinical Trials as Topic; Desmosine; Disease Models, Animal; Elastin; Glycosaminoglycans; Humans; Hyaluronic Acid; Immunity, Cellular; Isodesmosine; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Rats
PubMed: 29289686
DOI: 10.1016/j.chest.2017.12.016 -
Frontiers in Cardiovascular Medicine 2022Elastin degradation is implicated in the pathology of vulnerable plaque. Recent studies show promising results for plasma desmosine (pDES), an elastin-specific...
BACKGROUND
Elastin degradation is implicated in the pathology of vulnerable plaque. Recent studies show promising results for plasma desmosine (pDES), an elastin-specific degradation product, as a marker of cardiovascular disease (CVD) outcomes. The aim of this study was to investigate the potential role of pDES as a marker of clinical outcome in patients with acute myocardial infarction (AMI).
MATERIALS AND METHODS
In this case-control study, we studied 236 AMI patients: 79 patients who had death and/or myocardial infarction (MI) at 2 years, and 157 patients who did not have an event at 2 years. pDES was measured using a validated liquid chromatography-tandem mass spectrometry method. Association of pDES with adverse outcomes, and the incremental value of pDES to global registry of acute coronary events (GRACE) score for risk stratification was assessed.
RESULTS
pDES levels were elevated in patients with the composite outcome of death/MI at 2 years ( = 0.002). Logistic regression analyses showed pDES to be associated with death/MI at 2 years [Odds ratio (OR) 5.99 (95% CI 1.81-19.86) = 0.003]. pDES remained a significant predictor of death/MI at 2 years even after adjustment for age, sex, history of CVD, revascularisation, blood pressure, medications on discharge, Troponin I, and NT-proBNP levels.[OR 5.60 (95% CI 1.04-30.04) = 0.044]. In another multivariable model including adjustment for eGFR, pDES was significantly associated with the composite outcome at 6 months, but not at 2 years follow up. DES was also able to reclassify risk stratification for death/MI at 6 months, when added to the GRACE risk model [Net Reclassification Index (NRI) 41.2 (95% CI 12.0-70.4) = 0.006].
CONCLUSION
pDES concentrations predict clinical outcomes in patients with AMI, demonstrating its potential role as a prognostic marker in AMI.
PubMed: 36479574
DOI: 10.3389/fcvm.2022.992388 -
American Journal of Perinatology May 2024This study aimed to evaluate whether elevated urine desmosine levels at 3 weeks of age were associated with severe radiological findings, bronchopulmonary dysplasia...
OBJECTIVE
This study aimed to evaluate whether elevated urine desmosine levels at 3 weeks of age were associated with severe radiological findings, bronchopulmonary dysplasia (BPD), and post-prematurity respiratory disease (PRD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants.
STUDY DESIGN
This study recruited 37 EP (22-27 completed weeks) or ELBW (<1,000 g) infants. Urine was collected between 21 and 28 postnatal days, and desmosine was measured using an enzyme-linked immunosorbent assay kit; the urine creatinine level was also measured. Bubbly/cystic lungs were characterized by emphysematous chest X-rays on postnatal day 28. Furthermore, provision of supplemental oxygen or positive-pressure respiratory support at 40 weeks' postmenstrual age defined BPD, and increased medical utilization at 18 months of corrected age defined PRD. The desmosine/creatinine threshold was determined by receiver operating characteristic analysis. The adjusted risk and 95% confidence interval (CI) for elevated urine desmosine/creatinine levels were estimated by logistic regression analysis.
RESULTS
Elevated urine desmosine/creatinine levels higher than the threshold were significantly associated with bubbly/cystic lungs (8/13 [61.5%] vs. 2/24 [8.3%], = 0.001), BPD (10/13 [76.9%] vs. 8/24 [33.3%], = 0.02), and PRD (6/13 [46.2%] vs. 2/24 [8.3%], = 0.01). After adjusting for gestational age, birth weight, and sex, the urine desmosine/creatinine levels were significantly higher in those who were highly at risk of bubbly/cystic lungs (odds ratio [OR], 13.2; 95% CI, 1.67-105) and PRD (OR, 13.8; 95% CI, 1.31-144).
CONCLUSION
Elevated urine desmosine/creatinine levels on the third postnatal week were associated with bubbly/cystic lungs on day 28 and PRD at 18 months of corrected age in EP or ELBW infants.
KEY POINTS
· Urine desmosine was prospectively measured in 3-week-old EP/ELBW infants.. · Elevated urine desmosine levels were associated with emphysematous radiological findings on day 28, PRD at 18 months of corrected age.. · Urine desmosine may be a promising biomarker indicating lung damage in EP/ELBW infants..
Topics: Humans; Bronchopulmonary Dysplasia; Infant, Newborn; Female; Male; Biomarkers; Desmosine; Infant, Extremely Premature; Creatinine; Infant, Extremely Low Birth Weight; Gestational Age; Logistic Models; ROC Curve; Prospective Studies
PubMed: 36384237
DOI: 10.1055/a-1979-8501 -
Lung Dec 2018While the elastin-specific crosslinks, desmosine and isodesmosine (DID), are increased in blood, urine, and sputum of patients with clinically documented pulmonary...
PURPOSE
While the elastin-specific crosslinks, desmosine and isodesmosine (DID), are increased in blood, urine, and sputum of patients with clinically documented pulmonary emphysema, the usefulness of DID in detecting early lung injury remains untested. To this end, our laboratory has measured DID in a hamster model of smoke-induced emphysema, involving only minimal alveolar wall damage.
METHODS
Animals were either treated with cigarette smoke for 2 h/day, 5 days/week, or exposed only to room air (controls) for a period of 3 months. DID levels in bronchoalveolar lavage fluid (BALF) and whole lungs were determined at monthly intervals, using liquid chromatography and tandem mass spectrometry. Lung surface area was also determined, as a measure of airspace enlargement.
RESULTS
The portion of BALF DID not bound to peptides (free DID) was significantly higher in smoke-exposed animals at 2 months (9.2 vs 4.4 pg/mg protein; p < 0.05), whereas total BALF DID showed no significant increases over the course of the study, and total lung DID remained unchanged. There was a mild, but significant, loss of lung surface area in the smoke-exposed group at 2 months (28.8% vs 25.2%, p < 0.05), which showed no further progression, consistent with the return of free DID to control levels at 3 months.
CONCLUSIONS
These findings support the hypothesis that free DID are sensitive indicators of smoke-induced lung injury. Measurement of free DID in smokers with minimally decreased lung mass may help determine the utility of this parameter as a test for incipient pulmonary emphysema.
Topics: Animals; Biomarkers; Bronchoalveolar Lavage Fluid; Chromatography, Liquid; Desmosine; Disease Models, Animal; Female; Lung; Mesocricetus; Pulmonary Emphysema; Smoking; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Time Factors; Up-Regulation
PubMed: 30218154
DOI: 10.1007/s00408-018-0163-1