Lack of association between serum myonectin levels and sarcopenia in older Asian adults.

Myonectin is a muscle-secreted factor that helps maintain homeostasis in the body by regulating several functions, including lipid metabolism. Previous studies suggested that myonectin may play a role in muscle health in an autocrine manner, but its impact on human skeletal muscle is still unclear. We aimed to investigate the relationship of serum myonectin levels with sarcopenia and related muscle parameters. We conducted a cross-sectional study of 142 older adults whose muscle mass, grip strength, gait speed, chair stands, and short physical performance battery (SPPB) were evaluated in the geriatric clinic of a tertiary medical center. Sarcopenia was defined based on Asian-specific cutoff values, and circulating myonectin levels were measured using an enzyme immunoassay. Before and after adjusting for age, sex, and body mass index, the serum myonectin level was not significantly different when the patients were stratified by status of sarcopenia, muscle mass, muscle strength, and physical performance. Furthermore, whether given as a continuous variable or divided into quartile groups, the serum myonectin level had no association with the skeletal muscle mass, grip strength, gait speed, chair stand test, or SPPB score. Our findings did not confirm the potential role of myonectin in muscle metabolism observed in experimental research. Thus, serum myonectin levels cannot predict the risk of sarcopenia in older Asian adults.

Evaluation of changing the pattern of CTRP5 and inflammatory markers levels in patients with coronary artery disease and type 2 diabetes mellitus.

PURPOSE: It has recently found that adipokines, play a numerous functional roles in inflammation, lipids and glucose metabolism and in the pathogenically conditions such as atherosclerosis and insulin resistance. Therefore, for the first time we aimed the present study to evaluating serum levels of CTRP5 and inflammatory cytokines patients with CAD and T2DM in comparison with controls. METHODS: This study was done on 44 patients with CAD, 45 type 2 diabetes mellitus (T2DM), 41 CAD + T2DM and 41 controls. Serum levels of TNF-α, IL-6, MCP-1 and CTRP5 were investigated by ELISA method. RESULTS: The CTRP5 levels of all patients groups were lower in comparison with control group. There was a significant negative relationship between CTRP5 levels and cytokines concentration in the studied patients. CONCLUSIONS: Our findings suggested a potential role of CTRP5 in inflammatory process of underlying atherosclerosis and diabetes; however, more studies are needed to support these finding.

Increased serum myonectin and irisin levels with myonectin and FNDC5 expressions in polycystic ovary syndrome: a case control study.

The aim of this study is to assess the FNDC5 and myonectin expressions and serum levels of myonectin and irisin in women with PCOS. 90 participants were included in this case-control study. 45 of these participants were with PCOS, and 45 of them were healthy volunteers matched for age and body mass index (BMI). Serum irisin and myonectin levels were measured with commercially available enzyme-linked immune sorbent assay (ELISA) kits. Expression of the myonectin and FNDC5 genes were determined by RT-PCR analysis. It was found out that FSI, HOMA-IR, LH, LH/FSH, TT, serum irisin and serum myonectin levels, myonectin mRNA expression, and FNDC5 mRNA expression were higher in the PCOS group, whereas HDL-C level was lower in the PCOS group (p < .05). When the groups were compared, it was detected that IR and HA were significantly higher in the PCOS group (p < .05). Serum irisin and myonectin levels, and myonectin and FNDC5 mRNA expressions were increased in women with PCOS. These molecules can be target molecules in PCOS pathophysiology and treatment.IMPACT STATEMENTWhat is already known on this subject? Although the aetiology of PCOS is not fully understood, it is thought that insulin resistance may play a critical role. In recent studies, the relationship of cytokines secreted from skeletal muscle with insulin resistance has been shown. The effects of irisin and myonectin, which are members of the myokine family, on lipid and glucose metabolism are known.What do the results of this study add? Although there are many studies in the literature regarding serum irisin levels in women with PCOS, their results are confusing. There is a study in the literature investigating the relationship between myonectin and PCOS. In our study, we evaluated myonectin and FNDC mRNA expressions in addition to serum irisin and myonectin levels. As a result, we found that markers and their mRNA expressions were lower in patients with PCOS compared to controls.What are the implications of these findings for clinical practice and/or further research? We think that the results of our study will shed light on future studies. Due to their effects on adipose tissue, these markers may play a role in the aetiology of long-term complications of PCOS. Moreover, they can become pharmacological targets in preventing these complications.

Association of Tumor-Associated Collagen Signature With Prognosis and Adjuvant Chemotherapy Benefits in Patients With Gastric Cancer.

Importance: The current TNM staging system provides limited information for prognosis prediction and adjuvant chemotherapy benefits for patients with gastric cancer (GC). Objective: To develop a tumor-associated collagen signature of GC (TACSGC) in the tumor microenvironment to predict prognosis and adjuvant chemotherapy benefits in patients with GC. Design, Setting, and Participants: This retrospective cohort study included a training cohort of 294 consecutive patients treated between January 1, 2012, and December 31, 2013, from Nanfang Hospital, Southern Medical University, People's Republic of China, and a validation cohort of 225 consecutive patients treated between October 1, 2010, and December 31, 2012, from Fujian Provincial Cancer Hospital, Fujian Medical University, People's Republic of China. In total, 146 collagen features in the tumor microenvironment were extracted with multiphoton imaging. A TACSGC was then constructed using the least absolute shrinkage and selection operator Cox proportional hazards regression model in the training cohort. Data analysis was conducted from October 1, 2020, to April 30, 2021. Main Outcomes and Measures: The association of TACSGC with disease-free survival (DFS) and overall survival (OS) was assessed. An independent external cohort was included to validate the results. Interactions between TACSGC and adjuvant chemotherapy were calculated. Results: This study included 519 patients (median age, 57 years [IQR, 49-65 years]; 360 [69.4%] male). A 9 feature-based TACSGC was built. A higher TACSGC level was significantly associated with worse DFS and OS in both the training (DFS: hazard ratio [HR], 3.57 [95% CI, 2.45-5.20]; OS: HR, 3.54 [95% CI, 2.41-5.20]) and validation (DFS: HR, 3.10 [95% CI, 2.26-4.27]; OS: HR, 3.24 [95% CI, 2.33-4.50]) cohorts (continuous variable, P < .001 for all comparisons). Multivariable analyses found that carbohydrate antigen 19-9, depth of invasion, lymph node metastasis, distant metastasis, and TACSGC were independent prognostic predictors of GC, and 2 integrated nomograms that included the 5 predictors were established for predicting DFS and OS. Compared with clinicopathological models that included only the 4 clinicopathological predictors, the integrated nomograms yielded an improved discrimination for prognosis prediction in a C index comparison (training cohort: DFS, 0.80 [95% CI, 0.73-0.88] vs 0.78 [95% CI, 0.71-0.85], P = .03; OS, 0.81 [95% CI, 0.75-0.88] vs 0.80 [95% CI, 0.73-0.86], P = .03; validation cohort: DFS, 0.78 [95% CI, 0.70-0.87] vs 0.76 [95% CI, 0.67-0.84], P = .006; OS, 0.78 [95% CI, 0.69-0.86] vs 0.75 [95% CI, 0.67-0.84], P = .002). Patients with stage II and III GC and low TACSGC levels rather than high TACSGC levels had a favorable response to adjuvant chemotherapy (DFS: HR, 0.65 [95% CI, 0.43-0.96]; P = .03; OS: HR, 0.55 [95% CI, 0.36-0.82]; P = .004; dichotomized variable, P < .001 for interaction for both comparisons). Conclusions and Relevance: The findings suggest that TACSGC provides additional prognostic information for patients with GC and may distinguish patients with stage II and III disease who are more likely to derive benefits from adjuvant chemotherapy.

Characterization of the 'White' Appearing Clots that Cause Acute Ischemic Stroke.

OBJECTIVES: Most clots retrieved from patients with acute ischemic stroke are 'red' in color. 'White' clots represent a less common entity and their histological composition is less known. Our aim was to investigate the composition, imaging and procedural characteristics of 'white' clots retrieved by mechanical thrombectomy. MATERIALS AND METHODS: Seventy five 'white' thrombi were selected by visual inspection from a cohort of 760 clots collected as part of the RESTORE registry. Clots were evaluated histopathologically. RESULTS: Quantification of Martius Scarlett Blue stain identified platelets/other as the major component in 'white' clots' (mean of 55% of clot overall composition) followed by fibrin (31%), red blood cells (6%) and white blood cells (3%). 'White' clots contained significantly more platelets/other (p<0.001*) and collagen/calcification (p<0.001*) and less red blood cells (p<0.001*) and white blood cells (p=0.018*) than 'red' clots. The mean platelet and von Willebrand Factor expression was 43% and 24%, respectively. Adipocytes were found in four cases. 'White' clots were significantly smaller (p=0.016*), less hyperdense (p=0.005*) on computed tomography angiography/non-contrast CT and were associated with a smaller extracted clot area (p<0.001*) than 'red' clots. They primarily caused the occlusion of middle cerebral artery, were less likely to be removed by aspiration and more likely to require rescue-therapy for retrieval. CONCLUSIONS: 'White' clots represented 14% of our cohort and were platelet, von Willebrand Factor and collagen/calcification-rich. 'White' clots were smaller, less hyperdense, were associated with significantly more distal occlusions and were less successfully removed by aspiration alone than 'red' clots.

Temporal, spatial and gender-based dietary differences in middle period San Pedro de Atacama, Chile: A model-based approach.

To explore the possible emergence and lived consequences of social inequality in the Atacama, we analyzed a large set (n = 288) of incredibly well preserved and contextualized human skeletons from the broad Middle Period (AD 500-1000) of the San Pedro de Atacama (Chile) oases. In this work, we explore model-based paleodietary reconstruction of the results of stable isotope analysis of human bone collagen and hydroxyapatite. The results of this modeling are used to explore local phenomena, the nature of the Middle Period, and the interaction between local situations and the larger world in which the oases were enmeshed by identifying the temporal, spatial, and biocultural correlates and dimensions of dietary difference. Our analyses revealed that: 1) over the 600-year period represented by our sample, there were significant changes in consumption patterns that may evince broad diachronic changes in the structure of Atacameño society, and 2) at/near 600 calAD, there was a possible episode of social discontinuity that manifested in significant changes in consumption practices. Additionally, while there were some differences in the level of internal dietary variability among the ayllus, once time was fully considered, none of the ayllus stood out for having a more (or less) clearly internally differentiated cuisine. Finally, sex does not appear to have been a particularly salient driver of observed dietary differences here. While we do not see any de facto evidence for complete dietary differentiation (as there is always overlap in consumption among individuals, ayllus, and time periods, and as isotopic analysis is not capable of pinpointing different foods items or preparations), there are broad aspects of dietary composition changing over time that are potentially linked to status, and foreignness. Ultimately, these stand as the clearest example of what has been termed "gastro-politics," potentially tied to the emergence of social inequality in the San Pedro oases.

Association of serum and aqueous humor myonectin concentrations with diabetic retinopathy.

Myonectin, a newly discovered myokine, enhances fatty acid uptake in cultured adipocytes and hepatocytes and suppresses circulating levels of free fatty acids in mice. This study is performed to evaluate the association between serum and aqueous humor myonectin concentrations with diabetic retinopathy (DR). This study was performed in a population of 228 patients with type 2 diabetes (T2DM) and 72 control subjects. Diabetic patients were then divided into T2DM patients without DR, non-proliferative diabetic retinopathy (NPDR) patients, and proliferative diabetic retinopathy (PDR) patients. Serum and aqueous humor myonectin concentrations were significantly lower in the case group than in the control group. PDR patients showed significantly decreased serum and aqueous humor myonectin concentrations than in the other two T2DM patients. In addition, NPDR patients showed significantly lower serum and aqueous humor myonectin concentrations than T2DM patients without DR. Logistic regression analysis demonstrated that serum and aqueous humor myonectin was correlated with a decreased risk of T2DM and DR. Simple linear regression analysis showed that serum myonectin was negatively correlated with duration of disease, body mass index (BMI), and HbA1c. Duration of disease and BMI were still correlated with the serum myonectin after a multiple linear regression analysis. Aqueous humor myonectin was negatively correlated with duration of disease, systolic blood pressure (SBP), and diastolic blood pressure. Duration of disease and SBP was still correlated with the aqueous humor myonectin after a multiple linear regression analysis. Our investigation indicates an inverse association of serum and aqueous humor myonectin with DR.

Bone Health in Aging Men: Does Zinc and Cuprum Level Matter?

The aim of this study was to assess the associations of serum and bone zinc (Zn) and cuprum (Cu) with bone mineral density (BMD) and content (BMC), markers of bone turnover, and sex hormones. The study group comprised 144 men treated with total hip replacement due to hip osteoarthritis. We measured total, free, and bioavailable testosterone, estradiol, and sex-hormone-binding globulin (sex hormones), as well as parathyroid hormone, osteocalcin, carboxy terminal collagen crosslinks, and N-terminal propeptide of type I procollagen (markers of bone turnover). Total body BMD, BMC, total and visceral fat, and appendicular skeletal mass (ASM) were measured using dual-energy X-ray absorptiometry. ASM index, and total and visceral fat were positively correlated with BMD. Bone Zn correlated neither with sex hormones nor with bone turnover markers; however, it was positively associated both with BMD and with BMC, while bone Cu (as opposed to serum Cu) was not. In multiple regression, the ASM index, Zn/Cu ratio (in both the serum and the bone), and serum Cu concentration were significantly associated with BMD and BMC after adjustment for age and body mass index (BMI). Our results suggest that the Zn/Cu ratio in both the serum and the bone may exert a significant positive effect on total BMD and BMC.

Circulating Serum Myonectin Levels in Obesity and Type 2 Diabetes Mellitus.

OBJECTIVE: Myonectin is one of the myokines and has gained interest as a potential new strategy to combat obesity and its associated disorders, such as type 2 diabetes mellitus (T2DM).The objective of this study was to investigate circulating serum myonectin levels in nondiabetes and T2DM and elucidate possible relationships between serum myonectin levels and metabolic parameters in patients with T2DM. DESIGN: A total of 362 Chinese patients with T2DM and 100 age- and sex-matched healthy controls were recruited in this study. Clinical characteristics, blood biochemistry, and circulating myonectin levels were measured by enzyme-linked immunosorbent assay. RESULTS: Circulating myonectin levels were significantly decreased in T2DM compared with controls. Obese nondiabetic controls had significantly lower serum myonectin levels compared with lean nondiabetic controls. In diabetic patients, serum myonectin concentrations were significantly negatively correlated with body mass index (BMI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP), hemoglobin A1c (HbA1c), fasting insulin (Fins), the homeostatic model assessment of insulin resistance (HOMA-IR), visceral fat area, and subcutaneous fat area. After adjusting for covariates, multivariate stepwise regression analysis demonstrated that BMI, LDL-C, TG, HOMA-IR, and visceral fat were the main independent predictors of low serum myonectin concentrations. CONCLUSIONS: Circulating myonectin levels were decreased in T2DM patients and in obese subjects. Moreover, serum myonectin levels were correlated with metabolic markers of T2DM. These data suggest that myonectin may be a useful marker in predicting the development of obesity and T2DM.

Circulating CTRP6 Levels are Increased in Overweight or Obese Chinese Individuals and Associated with Insulin Resistance Parameters: A Pilot Study.

AIMS: CTRP6, a newly discovered adipokine, has been found to be a regulator for energy homeostasis. However, the association between circulating CTRP6 and obesity in humans is still unclear. METHODS: 256 individuals, including 185 overweight/obese (OW/OB) and 71 normal weight adults, were recruited for this study. Circulating concentrations of CTRP6 and adiponectin (Adipoq) were examined by ELISA. RESULTS: Serum CTRP6 levels in obese individuals were significantly increased compared with those in healthy individuals (506.1±134.9 vs.363.3±80.5 ng/mL, P<0.01). Conversely, serum Adipoq concentrations in OW/OB individuals were markedly decreased compared with healthy controls [20.8 (12.1-29.3) vs. 14.1 ( 8.61-17.7) ; P<0.01]. Correlation analysis revealed that there was a positive relationship between circulating CTRP6 and age, BMI, Fat%, LDL-C, TG, WHR, TC, FBG, FIns, HOMA-IR and HbA1c, but there was an inverse correlation with Adipoq and HDL-C. Logistic regression analysis revealed that high serum CTRP6 levels are markedly associated with OW/OB. Finally, ROC curve analysis showed that the cut-off value for serum CTRP6 for prediction of IR is 518 ng/mL. CONCLUSIONS: CTRP6 may be a marker related to OW/OB.

Elevated ectodomain of type 23 collagen is a novel biomarker of the intestinal epithelium to monitor disease activity in ulcerative colitis and Crohn's disease.

BACKGROUND: Impaired intestinal epithelial barrier is highly affected in inflammatory bowel disease. Transmembrane collagens connecting the epithelial cells to the extracellular matrix have an important role in epithelial cell homeostasis. Thus, we sought to determine whether the transmembrane type 23 collagen could serve as a surrogate marker for disease activity in patients with Crohn's disease and ulcerative colitis. METHODS: We developed an enzyme-linked immunosorbent assay to detect the ectodomain of type 23 collagen (PRO-C23) in serum, followed by evaluation of its levels in both acute and chronic dextran sulphate sodium colitis models in rats and human inflammatory bowel disease cohorts. Serum from 44 Crohn's disease and 29 ulcerative colitis patients with active and inactive disease was included. RESULTS: In the acute and chronic dextran sulphate sodium-induced rat colitis model, the PRO-C23 serum levels were significantly increased after colitis and returned to normal levels after disease remission. Serum levels of PRO-C23 were elevated in Crohn's disease (p < 0.05) and ulcerative colitis (p < 0.001) patients with active disease compared to healthy donors. PRO-C23 differentiated healthy donors from ulcerative colitis (area under the curve [AUC]: 0.81, p = 0.0009) and Crohn's disease (AUC: 0.70, p = 0.0124). PRO-C23 differentiated ulcerative colitis patients with active disease from those in remission (AUC: 0.75, p = 0.0219) and Crohn's disease patients with active disease from those in remission (AUC: 0.68, p = 0.05). CONCLUSION: PRO-C23 was elevated in rats with active colitis, and inflammatory bowel disease patients with active disease. Therefore, PRO-C23 may be used as a surrogate marker for monitoring disease activity in ulcerative colitis and Crohn's disease.

Correlation of serum myonectin concentrations with the presence and severity of obstructive sleep apnoea syndrome.

OBJECTIVE: Myonectin, a newly discovered myokine, enhances fatty acid uptake in cultured adipocytes and hepatocytes and suppresses circulating concentrations of free fatty acids in mice. This study is performed to evaluate the association between serum myonectin concentrations with the presence and severity of OSAS. METHODS: This study was performed in a population of 191 patients with OSAS and 105 control subjects. Serum myonectin concentrations were measured using enzyme-linked immunosorbent assay method. RESULTS: Lower serum myonectin concentrations were found in OSAS patients than in the controls. Serum myonectin concentrations were associated with a reduced risk of OSAS (OR: 0.988, 95% CI: 0.984-0.993, P < 0.001). Severe OSAS patients had significantly lower myonectin concentrations compared with mild and moderate OSAS patients (P < 0.001 and P = 0.001, respectively). There are lower serum myonectin concentrations in moderate patients compared with mild patients (P = 0.024). Pearson correlation analysis revealed that serum myonectin concentrations were negatively correlated with the severity of OSAS (r = -0.344, P < 0.001). Simple linear regression analysis showed that serum myonectin concentrations in OSAS patients were negatively correlated with body mass index, fasting plasma glucose, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C) and apnoea hypopnea index. Multiple stepwise regression analysis shows that body mass index (ß = -0.289, P = 0.03), HOMA-IR (ß = -0.19, P = 0.003), total cholesterol (ß = -0.155, P = 0.016), LDL-C (ß = -0.176, P = 0.006) and apnoea hypopnea index (ß = -0.263, P < 0.001) remained to be associated with serum myonectin. CONCLUSION: Serum myonectin concentrations are inversely correlated with the presence and severity of OSAS.

Advances in the clinical use of collagen as biomarker of liver fibrosis.

INTRODUCTION: Hepatic fibrosis is the excessive synthesis and deposition of extracellular matrix including collagen in the tissue. Chronic liver insult leads to progressive parenchymal damage, portal hypertension, and cirrhosis. Determination of hepatic collagen by invasive liver biopsy is the gold standard to estimate severity and stage of fibrosis. However, this procedure is associated with pain, carries the risk of infection and bleeding, and is afflicted with a high degree of sampling error. Therefore, there is urgent need for serological collagen-derived markers to assess collagen synthesis/turnover. AREAS COVERED: Biochemical properties of collagens, cellular sources of hepatic collagen synthesis, and regulatory aspects in collagen expression. Markers are discussed suitable to estimate hepatic collagen synthesis and/or turnover. Discussed studies were identified through a PubMed search done in May 2020 and the authors' topic knowledge. EXPERT OPINION: Hepatic fibrosis is mainly characterized by accumulation of collagen-rich scar tissue. Although traditionally performed liver biopsy is still standard in estimating hepatic fibrosis, there is evidence that noninvasive diagnostic scores and collagen-derived neo-epitopes provide clinical useful information. These noninvasive tests are less expensive than liver biopsy, better tolerated, safer, and more acceptable to patients. Therefore, these tests will lead to dramatic changes in diagnosis.

Decreased serum myonectin concentrations in diabetic nephropathy patients.

Myonectin is a newly discovered myokine correlated with diabetes. Diabetic nephropathy (DN), which is diagnosed according to albuminuria, is one of the most common microvascular complications of diabetes. Albuminuria predisposes to future cardiovascular diseases and mortality. The aim of this study is to assess the association between serum myonectin concentrations with DN. A total of 188 patients with type 2 diabetes (T2DM) and 66 control subjects were enrolled in this investigation. T2DM patients were divided into three groups: normoalbuminuria (n = 84), microalbuminuria (n = 70), and macroalbuminuria (n = 34) according to urine albumin-to-creatinine ratio (ACR). T2DM patients showed lower serum myonectin concentrations compared with the controls. Serum myonectin concentrations were significantly decreased in macroalbuminuria group than in normoalbuminuria and microalbuminuria groups. In addition, microalbuminuria group had decreased serum myonectin concentrations compared with normoalbuminuria group. Logistic regression analysis demonstrated a correlation between serum myonectin and a decreased risk of T2DM and DN. Simply linear regression analysis indicated serum myonectin was negatively correlated body mass index (BMI), total cholesterol, low-density lipoprotein cholesterol, blood urea nitrogen, creatinine, uric acid, and ACR, and positively correlated with glomerular filtration rate, insulin treatment. BMI, ACR, and insulin treatment were still correlated with the serum myonectin after a multiple linear regression analysis. Our investigation indicates serum myonectin is decreased in DN patients and correlated with renal function.

Serum myonectin is increased after laparoscopic sleeve gastrectomy.

OBJECTIVE: Myonectin, a newly discovered myokine, enhances fatty acid uptake in cultured adipocytes and hepatocytes and suppresses circulating levels of free fatty acids in mice. Recent studies showed that serum myonectin concentration is negatively correlated with obesity. This study was undertaken to evaluate the change of serum myonectin in obese patients after laparoscopic sleeve gastrectomy. METHODS: This study was performed in a population of 42 obese and 58 control subjects from April of 2018 to December of 2019. All obese subjects underwent laparoscopic sleeve gastrectomy. Anthropometric measurements, lipid profiles, HbA1c and serum myonectin were assessed at baseline and six months after laparoscopic sleeve gastrectomy. RESULTS: Serum myonectin concentrations were significantly lower in the obese patients than in the controls. Serum myonectin concentrations were increased at six months after laparoscopic sleeve gastrectomy. Simple linear regression analysis indicated that serum myonectin was negatively correlated with weight, waist circumference, hip circumference, body mass index, fasting plasma glucose, homeostasis model assessment of insulin resistance and HbA1c. Only body mass index was still inversely correlated with serum myonectin after multiple linear regression analysis. CONCLUSION: Serum myonectin is correlated with obesity and increased after laparoscopic sleeve gastrectomy.

Correlation of serum C1q-tumour necrosis factor-related protein 5 levels with metabolic parameters and carotid intima-media thickness in newly diagnosed type 2 diabetes mellitus patients.

PURPOSE: Recent studies have shown that cytokines secreted from adipose tissues play a role in the pathogenesis of type 2 diabetes mellitus (T2DM). CTRP5 (C1q-TNF-related protein 5) is a novel adipokine that has been shown to be associated with glucose and lipid metabolism. Varying levels of CTRP5 have been reported in individuals with diabetes, obesity and coronary artery disease. The aim of this study was to examine serum levels of CTRP5 and to show the relationship with cardiometabolic parameters in T2DM patients. METHOD: The study included 40 T2DM patients and 40 age- and sex-matched healthy control subjects. All the study participants were evaluated with respect to BMI, waist circumference, lipid profile, insulin resistance (HOMA-IR), serum CTRP5 levels, carotid intima-media thickness, and hs-CRP. RESULTS: No statistically significant differences were found between the control group and the diabetic group in terms of age, sex, or BMI. Serum CTRP5 levels (T2DM = 94.55 ± 28.70 ng/ml, control = 76.02 ± 27.22 ng/ml, P = 0.004*) were significantly higher in the group of newly diagnosed diabetic patients. A positive correlation was found between CTRP5 and the cardiometabolic parameters of carotid intima-media thickness (CIMT), hs-CRP, HOMA-IR and BMI. Regression analysis results showed that CTRP5 levels were independently correlated with insulin resistance estimated by HOMA-IR. CONCLUSION: Serum CTRP5 levels were correlated with cardiometabolic parameters and could therefore be a promising indicator of metabolic status and a possible biomarker of insulin resistance. However, the contradictory results reported in different studies indicate the need for further research to assess the significance of CTRP5 for diagnosis and monitoring of treatment efficacy.

Collagen methionine sulfoxide and glucuronidine/LW-1 are markers of coronary artery disease in long-term survivors with type 1 diabetes. The Dialong study.

OBJECTIVES: Type 1 diabetes is a risk factor for coronary heart disease. The underlying mechanism behind the accelerated atherosclerosis formation is not fully understood but may be related to the formation of oxidation products and advanced glycation end-products (AGEs). We aimed to examine the associations between the collagen oxidation product methionine sulfoxide; the collagen AGEs methylglyoxal hydroimidazolone (MG-H1), glucosepane, pentosidine, glucuronidine/LW-1; and serum receptors for AGE (RAGE) with measures of coronary artery disease in patients with long-term type 1 diabetes. METHODS: In this cross-sectional study, 99 participants with type 1 diabetes of ≥ 45-year duration and 63 controls without diabetes had either established coronary heart disease (CHD) or underwent Computed Tomography Coronary Angiography (CTCA) measuring total, calcified and soft/mixed plaque volume. Skin collagen methionine sulfoxide and AGEs were measured by liquid chromatography-mass spectrometry and serum sRAGE/esRAGE by ELISA. RESULTS: In the diabetes group, low levels of methionine sulfoxide (adjusted for age, sex and mean HbA1c) were associated with normal coronary arteries, OR 0.48 (95% CI 0.27-0.88). Glucuronidine/LW-1 was associated with established CHD, OR 2.0 (1.16-3.49). MG-H1 and glucuronidine/LW-1 correlated with calcified plaque volume (r = 0.23-0.28, p<0.05), while pentosidine correlated with soft/mixed plaque volume (r = 0.29, p = 0.008), also in the adjusted analysis. CONCLUSIONS: Low levels of collagen-bound methionine sulfoxide were associated with normal coronary arteries while glucuronidine/LW-1 was positively associated with established CHD in long-term type 1 diabetes, suggesting a role for metabolic and oxidative stress in the formation of atherosclerosis in diabetes.

Myocardial Interstitial Fibrosis in Nonischemic Heart Disease, Part 3/4: JACC Focus Seminar.

Myocardial interstitial fibrosis (MIF) is a histological hallmark of several cardiac diseases that alter myocardial architecture and function and are associated with progression to heart failure. MIF is a diffuse and patchy process, appearing as a combination of interstitial microscars, perivascular collagen fiber deposition, and increased thickness of mysial collagen strands. Although MIF arises mainly because of alterations in fibrillar collagen turnover leading to collagen fiber accumulation, there are also alterations in other nonfibrillar extracellular matrix components, such as fibronectin and matricellular proteins. Furthermore, in addition to an excess of collagen, qualitative changes in collagen fibers also contribute to the detrimental impact of MIF. In this part 3 of a 4-part JACC Focus Seminar, we review the evidence on the complex mechanisms leading to MIF, as well as its contribution to systolic and diastolic cardiac dysfunction and impaired clinical outcomes in patients with nonischemic heart disease.

Association of decreased myonectin levels with metabolic and hormonal disturbance in polycystic ovary syndrome.

Myonectin is a myokine involving in glucose and lipid metabolisms. Polycystic ovary syndrome (PCOS) is a metabolic and reproductive disorder associated with insulin resistance. Our aims were to discover whether myonectin levels were altered in PCOS women comparing to controls and to determine the link of myonectin with hormonal-metabolic parameters in PCOS women. The current research was designed as a case-control study. Seventy-two subjects with PCOS and 72 age- and body mass index (BMI)-matched subjects as controls were enrolled into the study. Circulating myonectin levels were measured by ELISA. Myonectin levels were significantly lower in PCOS subjects compared to controls (6.77 ± 1.96 vs. 9.14 ± 2.87 ng/ml, p< .001). Myonectin exhibited an inverse association with BMI, insulin resistance, free androgen index (FAI) and triglycerides whereas it showed a positive association with high-density lipoprotein cholesterol (HDL-C) in women with PCOS. Logistic regression analysis revealed that decreased myonectin levels were parallel with increased probability of having PCOS risk. Decreased myonectin levels were associated with metabolic and hormonal disturbances in PCOS women, suggesting that myonectin may play a role in pathophysiology of PCOS.

Excessively activated plasminogen in human plasma cleaves VWF multimers and reduces collagen-binding activity.

Plasmin (Pm) is a serine protease that can dissolve fibrin clots. Several possible functions of Pm in blood other than fibrinolysis have been proposed. To explore the effects of Pm on primary haemostasis, we evaluated the cleavage of von Willebrand factor multimers (VWFMs) in human plasma by streptokinase (SK)-activated plasminogen (Pg) and the binding ability of the digested VWFMs to collagen. SK-activated Pg and ADAMTS13 (a VWF-cleaving enzyme) in human plasma cleaved VWFMs in conformation-dependent manners through dialysis to the urea-containing buffer. However, VWFMs in human plasma under vortex-based shear stress were cleaved by SK-activated Pg but not by ADAMTS13. These results suggested that the VWFM-cleavage sites in human plasma are exposed to some extent by vortex-based shear stress for Pm but not for ADAMTS13. Additionally, we revealed that cleavage by SK-activated Pg reduced VWFMs' binding ability to collagen, and VWFMs in human plasma were cleaved by Pm at several sites. These results suggest that SK-activated Pg degrades VWFMs, reduces their binding abilities to collagen and affects primary haemostasis. Because excessive Pg activation can degrade fibrinogen/fibrin, we propose that SK-activated Pg in blood may cause impaired primary and secondary haemostasis.