C1q Tumor Necrosis Factor-related Protein Research Articles

Down regulation of C1q tumor necrosis factor-related protein 6 is associated with increased risk of breast cancer

C1q tumor necrosis factor-related protein 6 (CTRP6), a member of the C1q tumor necrosis factor-related protein (CTRP) family, is reported to be associated with the progression of different malignancies, however, its expression levels and role in breast cancer (BC) are yet unknown. In this study, we investigated the levels of circulating CTRP6 in BC patients and evaluated its role as a potential diagnostic biomarker in BC patients. Then we investigated the effect of recombinant CTRP6 on cellular viability in MCF-7 cells along with its effects on the expression of inflammatory cytokines, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) in addition to the expression of vascular endothelial growth factor (VEGF) as a marker of angiogenesis. Our results showed decreased expression of circulating CTRP6 in BC patients with an inverse correlation between CTRP6 and IL-6, TNF-α and VEGF levels. Besides, Receiver operating characteristic (ROC) curve showed that the assessment of CTRP6 levels could be used to predict BC. Moreover, treatment of MCF-7 cells with recombinant CTRP6 protein reduced cellular viability and decreased IL-6, TNF-α and VEGF expression. In conclusion, these results provide new insights into the role of CTRP6 in BC pathogenesis and suggest its potential use as a novel diagnostic biomarker of BC.

#197 : The Associations Between Modifiable Risk Factors and Spontaneous Abortion: A Two-Sample Mendelian Randomization Study

Back and Aims: Early identification of modifiable risk factors is essentialfor the prevention of spontaneous abortion (SA). We aimed to systematically explore the relationships between genetically predicted modifiable risk factors and SA. Method: We obtained genetic variants associated with the modifiable risk factors at the genome-wide significance (p< 5× [Formula: see text]) level from genome-wide association studies (GWAS). Two-sample Mendelian Randomization (MR) analysis was used to investigate the relationship between 42 modifiable risk factors and SA. Results: The studyfound that genetically predicted HLA DR++ monocyte %leukocyte, HLA DR on CD14+ monocyte, HLA DR on monocyte, and type of transport used were associated with an increased risk of SA (all with [OR]>1 and p< 0.05). Conversely, CD14+ CD16- monocyte absolute count, age first had sexual intercourse, never smoked, and education status were found to be negatively associated with SA (all with [OR]<1 and p< 0.05). Additionally, the study observed potential associations between genetically predicted CD25 on switched memory B cell, lymphocyte count, monocyte absolute count, CD8+ natural killer T %T cell, asthma, appendicular lean mass, rheumatoid arthritis, complement C1q tumor necrosis factor-related protein 1 (CTRP1), hand grip strength, waist-to-hip ratio, and usual walking pace with an increased risk of SA. Conversely, lymphocyte count was associated with a suggestive lower risk of SA in the results. Conclusion: Our analysis revealed that several modifiable risk factors were associated with SA. Specifically, genetically predicted a higher proportion of HLA DR++ monocytes in leukocytes, HLA DR on CD14+ monocyte, HLA DR on monocyte and often using cycle as transportation were associated an increased risk of SA, while evaluated CD14+ CD16- monocyte absolute count, first sexual intercourse at an older age, never smoked, and higher education were with a decreased risk of SA.

C1q tumor necrosis factor related proteins (CTRPs) in patients with cardiovascular diseases

Cardiovascular diseases (CVDs) are the major cause of death in both developed and developing countries. It is widely accepted that predicting CVDs in the early stages or before the onset of the diseases could be a central goal in the management, prevention, and treatment of these diseases. Adipokines, a large and diverse group of molecules secreted by adipose tissue that affect cardiovascular function, have played a crucial role in the cardiovascular system. C1q/tumor necrosis factor-related protein (CTRP) is a newly discovered family of adipokines that are paralogs of adiponectin. This family includes 15 members (CTRP1 to CTRP15). Recent studies have shown that CTRPs have diverse biological effects on the cardiovascular system. In this review, recent research on the expression of the CTRP gene superfamily in CVDs is examined to assess their potential as new CVD biomarkers. Given the growing data on the roles of CTRPs in the physiology and development of CVDs, this review discusses the role of various types of CTRPs, including CTRP1, CTRP2, CTRP3, CTRP6, CTRP9, CTRP12, and CTRP13 in the management, prevention, and treatment of CVDs.

The association between complement C1q tumour necrosis factor-related protein-1 (CTRP-1) level and metabolic syndrome.

Complement C1q tumour necrosis factor-related protein (CTRP-1) is a member of the C1q protein superfamily that plays a role in metabolism. This retrospective study aimed to investigate associations between CTRP-1 and metabolic syndrome (MetS). This study screened subjects who had undergone regular health examinations at the Physical Examination Centre in the First People's Hospital of Yinchuan (the Second Affiliated Hospital of Ningxia Medical University) between November 2017 and September 2020. The total recruited population included 430 subjects who had undergone regular health examinations, excluding 112 subjects with high glycated haemoglobin (HbA1c ≥ 7). Finally, the data of 318 participants were further analysed. Non-diabetic subjects were divided into 2 groups: one with MetS and one without MetS (controls). Serum CTRP-1 concentrations were evaluated using an enzyme-linked immunosorbent assay. A total of 318 subjects were included, among whom 176 were diagnosed with MetS (MetS group) and 142 were not (non-MetS controls). The MetS group had significantly lower CTRP-1 levels than non-MetS controls (128.51 [111.56-143.05] vs. 138.82 [122.83-154.33] ng/mL, p < 0.001). Correlation analysis showed that serum CTRP-1 levels correlated negatively with body mass index (r = -0.161, p = 0.004), waist circumference (r = -0.191, p = 0.001), systolic blood pressure (r = -0.198, p < 0.001), diastolic blood pressure (r = -0.145, p = 0.010), fasting blood glucose (FBG) (r = -0.562, p < 0.001), fasting insulin (FIns) (r = -0.424, p < 0.001), and homeostasis model assessment of insulin resistance (HOMA-IR) (r = -0.541, p < 0.001). Multiple linear regression models showed that CTRP-1 levels were associated with MetS (p < 0.01). The lipid profile area under the curve (AUC) was comparable to those for FBG and FIns, and it was significantly higher than the AUCs for demographic variables. The results of this study suggest that the serum CTRP-1 level is negatively associated with MetS. CTRP-1 is a potential metabolism-related protein and is likely to be associated with lipid profiles in MetS.

C1q/TNF-Related Proteins 1, 6 and 8 Are Involved in Corneal Epithelial Wound Closure by Targeting Relaxin Receptor RXFP1 In Vitro.

Inadequate wound healing of ocular surface injuries can lead to permanent visual impairment. The relaxin ligand-receptor system has been demonstrated to promote corneal wound healing through increased cell migration and modulation of extracellular matrix formation. Recently, C1q/tumor necrosis factor-related protein (CTRP) 8 was identified as a novel interaction partner of relaxin receptor RXFP1. Additional data also suggest a role for CTRP1 and CTRP6 in RXFP1-mediated cAMP signaling. However, the role of CTRP1, CTRP6 and CTRP8 at the ocular surface remains unclear. In this study, we investigated the effects of CTRP1, CTRP6, and CTRP8 on epithelial ocular surface wound closure and their dependence on the RXFP1 receptor pathway. CTRP1, CTRP6, and CTRP8 expression was analyzed by RT-PCR and immunohistochemistry in human tissues and cell lines derived from the ocular surface and lacrimal apparatus. In vitro ocular surface wound modeling was performed using scratch assays. We analyzed the effects of recombinant CTRP1, CTRP6, and CTRP8 on cell proliferation and migration in human corneal and conjunctival epithelial cell lines. Dependence on RXFP1 signaling was established by inhibiting ligand binding to RXFP1 using a specific anti-RXFP1 antibody. We detected the expression of CTRP1, CTRP6, and CTRP8 in human tissue samples of the cornea, conjunctiva, meibomian gland, efferent tear ducts, and lacrimal gland, as well as in human corneal, conjunctival, and meibomian gland epithelial cell lines. Scratch assays revealed a dose-dependent increase in the closure rate of surface defects in human corneal epithelial cells after treatment with CTRP1, CTRP6, and CTRP8, but not in conjunctival epithelial cells. Inhibition of RXFP1 fully attenuated the effect of CTRP8 on the closure rate of surface defects in human corneal epithelial cells, whereas the CTRP1 and CTRP6 effects were not completely suppressed. Conclusions: Our findings demonstrate a novel role for CTRP1, CTRP6, and CTRP8 in corneal epithelial wound closure and suggest an involvement of the relaxin receptor RXFP1 signaling pathway. This could be a first step toward new approaches for pharmacological and therapeutic intervention.

C1q/TNF-related protein 3 alleviates heart failure via attenuation of oxidative stress in myocardial infarction rats

C1q-tumor necrosis factor-related protein 3 (CTRP3), an adipokine, has been reported to be closely related to cardiovascular diseases (CVDs). However, the effect of CTRP3 on heart failure (HF) remains dimness. This study was to explore the role of CTRP3 in HF and its potential interaction mechanism. Heart failure model was established by inducing ischemia myocardial infarction (MI) through ligation of the left anterior descending artery in Sprague-Dawley rats. Four weeks later, the rats were detected by transthoracic echocardiography and masson staining. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cardiac troponin I (cTnI) levels, creatine kinase-MB (CK-MB) and oxidative stress levels were recorded. The level of CTRP3 was reduced in the cardiomyocytes (CMs) treated with oxygen-glucose deprivation (OGD) and in the heart of MI rats. CTRP3 overexpression alleviated cardiac dysfunction, attenuated the cardiac fibrosis, and inhibited the increases of ANP, BNP, cTnI and CK-MB in the serum of MI rats. The increases of ANP and BNP in the CMs, and the collagen I and collagen III in the cardiac fibroblasts (CFs) induced by OGD were inhibited by CTRP3 overexpression. The enhancement of oxidative stress in the heart of MI rats was inhibited by CTRP3 overexpression. These results indicated that overexpression of CTRP3 could improve cardiac function and the related cardiac fibrosis in MI-induced HF rats via inhibition of oxidative stress. Upregulation of CTRP3 may be a strategy for HF therapy in the future.

In Silico Pan-Cancer Analysis Reveals Prognostic Role of the Erythroferrone (ERFE) Gene in Human Malignancies.

The erythroferrone gene (ERFE), also termed CTRP15, belongs to the C1q tumor necrosis factor-related protein (CTRP) family. Despite multiple reports about the involvement of CTRPs in cancer, the role of ERFE in cancer progression is largely unknown. We previously found that ERFE was upregulated in erythroid progenitors in myelodysplastic syndromes and strongly predicted overall survival. To understand the potential molecular interactions and identify cues for further functional investigation and the prognostic impact of ERFE in other malignancies, we performed a pan-cancer in silico analysis utilizing the Cancer Genome Atlas datasets. Our analysis shows that the ERFE mRNA is significantly overexpressed in 22 tumors and affects the prognosis in 11 cancer types. In certain tumors such as breast cancer and adrenocortical carcinoma, ERFE overexpression has been associated with the presence of oncogenic mutations and a higher tumor mutational burden. The expression of ERFE is co-regulated with the factors and pathways involved in cancer progression and metastasis, including activated pathways of the cell cycle, extracellular matrix/tumor microenvironment, G protein-coupled receptor, NOTCH, WNT, and PI3 kinase-AKT. Moreover, ERFE expression influences intratumoral immune cell infiltration. Conclusively, ERFE is aberrantly expressed in pan-cancer and can potentially function as a prognostic biomarker based on its putative functions during tumorigenesis and tumor development.

IFI44L and C1QTNF5 as promising biomarkers of proliferative diabetic retinopathy.

Proliferative diabetic retinopathy (PDR) is a world-wide leading cause of blindness among adults and may be associated with the influence of genetic factors. It is significant to search for genetic biomarkers of PDR. In our study, we collected genomic data about PDR from gene expression omnibus (GEO) database. Differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) were carried out. The gene module with the highest gene significance (GS) was defined as the key module. Hub genes were identified by Venn diagram. Then we verified the expression of hub genes in validation data sets and built a diagnostic model by least absolute shrinkage and selection operator (LASSO) regression. Enrichment analysis, including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA) and construction of a protein-protein interaction (PPI) network were conducted. In GSE60436, we identified 466 DEGs. WGCNA established 14 gene modules, and the blue module (GS = 0.64), was the key module. Interferon (IFN)-induced protein 44-like (IFI44L) and complement C1q tumor necrosis factor-related protein 5 (C1QTNF5) were identified as hub genes. The expression of hub genes in GEO datasets was verified and a diagnostic model was constructed by LASSO as follows: index = IFI44L * 0.0432 + C1QTNF5 * 0.11246. IFI44L and C1QTNF5 might affect the disease progression of PDR by regulating metabolism-related and inflammatory pathways. IFI44L and C1QTNF5 may play important roles in the disease process of PDR, and a LASSO regression model suggested that the 2 genes could serve as promising biomarkers of PDR.

C1QL1/CTRP14 Is Largely Dispensable for Atherosclerosis Formation in Apolipoprotein-E-Deficient Mice.

The purpose of this study was to investigate the influence of C1QL1 on atherosclerosis as well as the transcriptomic alteration of the aorta. While complement C1ql-like 1 (C1QL1) is one of the C1q/tumor-necrosis-factor-related protein (CTRP) family members, also known as CTRP14, and is synthesized and secreted mainly by the brain and adipose tissues, the functional properties of the C1QL1/CTRP14 protein outside the brain and adipocytes remain, however, unknown. In this regard, apolipoprotein E (ApoE) knockout (KO) mice were fed a Western diet and injected with adenovirus (Ad) green fluorescent protein or Ad-C1QL1 through the tail vein for 12 weeks. In contrast with the control cohort, the area of atherosclerotic plaque in ApoE KO mice overexpressing C1QL1 showed no significant difference, and the RNA sequence revealed that there were only 111 differentially expressed genes (DEGs) enriched in 26 signaling pathways of the mRNA profile in the aortic atherosclerosis lesions. This analysis also revealed the expression of several genes related to metabolism, organismal system, and human diseases such as type II diabetes, which are not associated with the formation of atherosclerosis in the aorta. These findings illustrate that C1QL1 is largely dispensable for atherosclerosis formation in ApoE-deficient mice and does not improve atherosclerotic plaque formation in the aorta.

Astragaloside IV Regulates Insulin Resistance and Inflammatory Response of Adipocytes via Modulating CTRP3 and PI3K/AKT Signaling.

Emerging evidence showed that adipocytes are important regulators in controlling insulin resistance in type 2 diabetes mellitus (T2DM). So far, compounds isolated from natural plants have been widely studied for their roles in alleviating T2DM-associated complications. This work evaluated the actions of astragaloside IV (AS-IV) on insulin resistance and inflammatory biomarker expression in adipocytes and explored the potential mechanisms. Glucose consumption of the adipocytes was determined by a glucose assay kit; the mRNA expression levels of glucose transporter type 4 (GLUT-4), interleukin-6 (IL-6), TNF-α and C1q tumor necrosis factor-related protein 3 (CTRP3) were measured by quantitative real-time PCR (qRT-PCR); the protein levels were determined by western blot assay and enzyme-linked immunosorbent assay. AS-IV concentration-dependently increased glucose consumption in the insulin resistance adipocytes. Further qRT-PCR results showed that AS-IV concentration-dependently reduced adipocyte IL-6 and TNF-α expression. Moreover, GLUT-4 expression in adipocytes was also significantly upregulated by AS-IV. Furthermore, we found that AS-IV concentration-dependently increased CTRP3 expression in adipocytes. CTRP3 silence decreased glucose consumption, upregulated IL-6 and TNF-α expression and downregulated GLUT-4 mRNA expression in 200µM AS-IV-treated adipocytes. Moreover, AS-IV treatment enhanced the activity of phosphoinositide 3-kinase (PI3K)/AKT signaling in adipocytes, which was markedly attenuated by CTRP3 silencing. Importantly, inhibition of PI3K/AKT signaling also attenuated AS-IV induced an increase in glucose consumption and GLUT-4 expression and a decrease in IL-6 and TNF-α expression of adipocytes. Collectively, our data indicated that AS-IV attenuated insulin resistance and inflammation in adipocytes via targeting CTRP3/PI3K/Akt signaling.

C1q tumor necrosis factor-related protein 4 is associated with coronary artery disease in patients with type 2 diabetes.

Aims/IntroductionTo evaluate the correlation of circulating C1q tumor necrosis factor‐related protein 4 (CTRP4) with coronary artery disease (CAD) in type 2 diabetes mellitus patients.MethodsA total of 240 individuals with type 2 diabetes mellitus were enrolled in our center between January 2020 and December 2020. They were assigned into two groups, including the CAD and non‐CAD groups, based on coronary angiography or computed tomography angiography findings. Serum CTRP4 levels were detected by an enzyme‐linked immunosorbent assay kit. The association of CTRP4 with CAD was determined by logistic regression analysis. The predictive value of CTRP4 for CAD was calculated by receiver operating characteristic curve analysis.ResultsMedian serum CTRP4 amounts were markedly elevated in the CAD group in comparison with the non‐CAD group (10.37 vs 3.75 ng/mL, P < 0.01). Binary logistic regression showed that CTRP4 was associated with CAD and even the amount of coronary artery lesions (P < 0.05). In receiver operating characteristic curve analysis, the area under the receiver operating characteristic curve was greater for CTRP4 compared with HbA1c or CRP (0.87 vs 0.74, 0.87 vs 0.80, P < 0.01). The area under the curve for CTRP4 and glycated hemoglobin in combination was larger than that obtained for CTRP4 combined with CRP (0.91 vs 0.87, P < 0.01). According to the maximum Youden index criteria, the optimal cut‐off of CTRP4 was 5.42 ng/mL, which yielded a sensitivity of 84.4% and a specificity of 76.7% in predicting CAD in type 2 diabetes mellitus patients.ConclusionsSerum CTRP4 levels are positively correlated with CAD occurrence and severity. Combining CTRP4 and glycated hemoglobin has a better predictive value for CAD in type 2 diabetes mellitus patients.

Novel biomarkers in systemic sclerosis

Introduction. Due to the heterogeneous nature of systemic sclerosis, it is difficult to predict disease progression and complications. Despite the discovery of novel autoantibodies associated with systemic sclerosis (SSc), there is an unmet need for biomarkers for diagnosis, disease progression, and response to treatment. Materials and methods. An analytical, qualitative study was performed with a narrative review of literature in the form of a synthesis article. Relevant primary sources published in 2020-2022 were identified and selected, using data extraction and analysis. Results. Anti-citrullinated protein/peptide antibody could be useful in identifying patients with a more prominent joint disease. Of most interest, the anti-carbamylated protein antibodies (anti-CarP) could be a relevant biomarker related to fibrotic skin and lung disease. Positive anti-RNA (Ribonucleic acid) polymerase III antibody and antinuclear antibodies (ANA) negativity were significantly associated with GAVE (gastral antral vascular ectasia). Autoantibodies against telomeres may help identify systemic sclerosis with lung disease. Osteopontin links myeloid activation and disease progression in systemic sclerosis. CTRP (C1q tumor necrosis factor-related proteins) 9 protein levels may be biomarker of lung disease severity. CD (cluster differentiation) 21-low B cells are linked to vascular damage. L-tyrosine, L-tryptophan, and 1-methyl-adenosine distinguished healthy controls from SSc patients. L-leucine, L-isoleucine, xanthosine, and adenosine monophosphate differentiated between progressing and stable SSc-ILD. CECs (circulating endothelial cells) are a direct indicator of systemic vascular damage. Levels of the protein, galectin-3, are associated with heart involvement in people with systemic sclerosis. Low levels of the galectin-10 protein (Gal-10) in scleroderma patients associate with inflammation and vascular changes in the lungs, leading to pulmonary arterial hypertension (PAH). High levels of the CD146 protein may be a potential biomarker in identifying people with systemic sclerosis. Blood levels of the protein endocan increased in scleroderma patients who are at risk for pulmonary arterial hypertension. FLCs (free light chain) could be employed as useful potential biomarker of early diagnosis and to follow disease activity. Conclusions. Novel discovered biomarkers could predict disease development, activity, and severity of diverse organ involvement, predict risk of complications of systemic sclerosis.

Adipokines, adiposity, and atherosclerosis.

Characterized by a surplus of whole-body adiposity, obesity is strongly associated with the prognosis of atherosclerosis, a hallmark of coronary artery disease (CAD) and the major contributor to cardiovascular disease (CVD) mortality. Adipose tissue serves a primary role as a lipid-storage organ, secreting cytokines known as adipokines that affect whole-body metabolism, inflammation, and endocrine functions. Emerging evidence suggests that adipokines can play important roles in atherosclerosis development, progression, as well as regression. Here, we review the versatile functions of various adipokines in atherosclerosis and divide these respective functions into three major groups: protective, deteriorative, and undefined. The protective adipokines represented here are adiponectin, fibroblast growth factor 21 (FGF-21), C1q tumor necrosis factor-related protein 9 (CTRP9), and progranulin, while the deteriorative adipokines listed include leptin, chemerin, resistin, Interleukin- 6 (IL-6), and more, with additional adipokines that have unclear roles denoted as undefined adipokines. Comprehensively categorizing adipokines in the context of atherosclerosis can help elucidate the various pathways involved and potentially pave novel therapeutic approaches to treat CVDs.

Potential participation of CTRP6, a complement regulator, in the pathology of age related macular degeneration.

To investigate the localized expression of C1q/tumor necrosis factor related protein (CTRP) 6 in human age-related macular degeneration (AMD) retinal tissues. 4 AMD and 3 non-AMD whole eyes of Caucasian donors were used. Eyecups were excised at Eye Bank CorneaGen, Inc. To elucidate the effects of CTRP6, C3b was measured by an enzyme-linked immunosorbent-like assay. CFB versus CTRP6 competitive binding assay was applied to clarify the inhibition by CTRP6 of C3bBb complex formation. The cornea, iris, lens, and vitreous were removed and the eyes were cut into a posterior eye-cup including the retina, choroid, and sclera. Six-µm-thick serial sections of frozen samples underwent hematoxylin-eosin (HE) staining and indirect immunohistochemical staining using primary antibodies, anti-CTRP6, -CTRP5, -CTRP10, -Complement factor H (CFH) and -Clusterin (CLU). Results The two in vitro studies confirmed that CTRP6 has an inhibitory effect on alternative pathways of complement (APC) function and that the molecular target of CTRP6 is the inhibition of the formation of C3bBb. Localized expression for CTRP6 and CFH was found in the drusen of the AMD eyes, both associated with APC inhibition, CLU associated with membrane-attack complex (MAC) inhibition, and CTRP5 associated with retinal degeneration. The localized expression of CTRP6 in the drusen of AMD eyes may open a new insight into the possible involvement of APC regulatory factors in the pathogenesis of AMD, together with the known CFH so far analyzed solely as an APC inhibitor.

CTRP15 promotes macrophage cholesterol efflux and attenuates atherosclerosis by increasing the expression of ABCA1.

C1q tumor necrosis factor-related protein 15 (CTRP15), a newly identified myokine, is closely implicated in cardiovascular disease. However, the role of CTRP15 in atherosclerosis is still unclear. This study aims to determine the role of CTRP15 in atherosclerosis and explore the underlying mechanisms. Our findings revealed that lentivirus-mediated CTRP15 overexpression significantly decreased atherosclerotic plaque lesions and increased reverse cholesterol transport (RCT) efficiency and circulating HDL-C levels in apolipoprotein E-deficient (apoE-/-) mice. Consistently, in vitro, overexpression of CTRP15 also inhibited intracellular lipid accumulation and promoted cholesterol efflux from macrophages. Mechanistically, CTRP15 decreased the expression of miR-101-3p by upregulating T-cadherin, thereby facilitating ABCA1 expression and cholesterol efflux. In summary, these data indicate that CTRP15 inhibits the development of atherosclerosis by enhancing RCT efficiency and increasing plasma HDL-C levels via the T-cadherin/miR-101-3p/ABCA1 pathway. Targeting CTRP15 may serve as a novel and promising therapeutic strategy for atherosclerotic cardiovascular diseases.

Predictive model for early complications of acute myocardial infarction in patients with type 2 diabetes mellitus

Introduction: Early complications of acute myocardial infarction (AMI) are one of the leading causes of death among patients with type 2 diabetes mellitus (DM). Clinical and laboratory characteristics and noninvasive methods need to be integrated to better identify early complications of AMI and further develop a treatment strategy. The aim of the study was to predict the development of early complications after AMI in type 2 DM patients, which could improve the quality of preventive and curative measures for this group of patients. Methods: In total, 109 patients with ST-elevation myocardial infarction (STEMI) and type 2 DM were included in the study: 75 men and 34 women. The training set (n = 74) was selected to study variables associated with the probability of early complications after AMI in type 2 DM patients. The model reproducibility was then checked on the validation set (n = 35). All patients underwent percutaneous coronary intervention (PCI). The training set identified 26 patients with early complications and 48 patients without early complications of AMI. The validation set identified 18 patients with early complications and 17 patients without early complications of AMI. The model for predicting early AMI complications was calculated using binary logistic regression. Results: The developed mathematical model for predicting early complications of AMI was as follows: Р = [1+ exp(- (0.030 C1q tumor necrosis factor-related protein 3 (CTRP 3) (ng/ml) + 1.414 x respiratory rate (RR) (breaths per minute) + 0.322 x body mass index (BMI) (kg/m2) + 0.091heart rate (HR) (beats per minute) -50.800))]-1. The model yielded the highest results under the receiver operating characteristic curve for predicting early complications of AMI among the diabetic patients in both the training and validation groups (0.962 and 0.928, respectively). Conclusions: This study has shown that integral measurements of circulating CTRP 3 content, RR, BMI, and HR upon admission of STEMI patients with type 2 DM after PCI could predict early complications of AMI. These findings suggest a new approach to stratify the risk of early AMI complications in type 2 DM patients after successful coronary revascularization.

Low Complement C1q/TNF-related Protein-13 Levels are Associated with Childhood Obesity But not Binge Eating Disorder

Objective:C1q/tumor necrosis factor-related proteins (CTRPs) are recently described members of the adipokine family. CTRP-13, a new member of this family, has been shown to increase insulin sensitivity and had an anorexigenic effect on food intake in experimental studies. The aim was to investigate serum CTRP-13 levels in children with obesity, and its relationship with other adipokines, metabolic parameters, or binge eating disorder (BED).Methods:A cross-sectional study was conducted with 105 pubertal children attending a single center. Clinical (metabolic syndrome, BED) and biochemical (glucose, insulin, lipids, leptin, adiponectin, CTRP-13 levels) parameters were assessed.Results:Sixty children with obesity [24 males (40%); median age 14.7 (13.0-16.4) years] and 45 healthy controls [15 males (33.3%); median age 15.2 (14.1-16.5) years] were included. Serum adiponectin and CTRP-13 levels were significantly lower in children with obesity than controls (7.1 vs 20.1 μg/mL, p<0.001; 64.7 vs 103.8 ng/mL, p<0.001, respectively). CTRP-13 levels correlated negatively with body mass index (Spearman rho=-0.230, p=0.018) and positively with high-density lipoprotein-cholesterol levels (Spearman rho=0.218, p=0.026). There was no significant difference in serum CTRP-13 concentrations in terms of the presence of metabolic syndrome or BED.Conclusion:Childhood obesity seems to be causing dysregulation in adipokine production and function, including the down-regulation of CTRP-13. The positive correlation between CTRP-13 and HDL-C levels suggested a possible effect of this adipokine on lipid metabolism. Thus CTRP-13 may be a novel biomarker for dyslipidemia in childhood obesity.

C1q/tumor necrosis factor related protein 6 (CTRP6) regulates the phenotypes of high glucose-induced gestational trophoblast cells via peroxisome proliferator-activated receptor gamma (PPARγ) signaling

ABSTRACT Multiple studies have confirmed that adipokines are compactly relevant to insulin resistance and participate in the pathogenesis of gestational diabetes mellitus (GDM). This paper aimed to study the effects of C1q/tumor necrosis factor related protein (CTRP)6 on the phenotypes of trophoblast cells, covering cell proliferation, invasion and migration, and initially explore the mechanism. High glucose was used to induce trophoblast cells to establish an in vitro model. The expression levels of CTRP6 were firstly determined, and then the effects of CTRP6 knockdown on cell viability, apoptosis, migration and invasion were assessed using CCK8, TUNEL, wound healing, Transwell assays. Moreover, the role of peroxisome proliferator-activated receptor gamma (PPARγ), probable target of CTRP6, was evaluated through co-transfection with PPARγ overexpression vector. The results of the present study revealed that CTRP6 and PPARγ were both upregulated in high glucose-induced cells. And CTRP6 knockdown could significantly elevate the abilities of cell viability, migration and invasion, and avoid cell apoptosis. In addition, PPARγ overexpression was found to restrain the protective effects of CTRP6 knockdown on the above aspects, indicating CTRP6 played a role in trophoblast cells via inhibiting PPARγ expression. In conclusion, CTRP6 regulated the viability, migration and invasion of high glucose-induced gestational trophoblast cells through PPARγ signaling.

Updates in diabetic neuropathy: A call for new diagnostic and treatment approaches.

Diabetic polyneuropathy (DPN) is a serious complication of both type 1 and type 2 diabetes. The major clinical manifestations of DPN are neuropathic pain, diabetic foot (which is associated with ulcers, gangrene, and amputation), and autonomic neuropathy. Diabetic sensorimotor peripheral neuropathy (DSPN) is the most common form of DPN and affects approximately 50% of people with type 1 or 2 diabetes during their lifetime (1) . Despite its major clinical impact, DPN remains underdiagnosed and undertreated. To reduce the burdens of DPN, there is an urgent need to develop both novel diagnostic procedures that enable to improve the early detection of the disease and new treatments that address multiple mechanistic pathways (Figure) (2) .

C1q Tumor Necrosis Factor-Related Protein 1: A Promising Therapeutic Target for Atherosclerosis.

Atherosclerosis serves as the pathological basis of most cardiovascular and cerebrovascular diseases. C1q tumor necrosis factor-related protein 1 (CTRP1) is a 35-kDa glycoprotein synthesized by various tissues and cells, such as adipose tissue and macrophages. As an adiponectin paralog, CTRP1 signals through adiponectin receptor 1 and participates in a variety of pathophysiological processes. Circulating CTRP1 levels are significantly increased in patients with coronary artery disease. Importantly, CTRP1 was shown to accelerate the development of atherosclerosis by promoting vascular inflammation, macrophage foam cell formation, and endothelial barrier dysfunction. This review focused on recent advances regarding the role of CTRP1 in atherogenesis with an emphasis on its potential as a novel biomarker and a promising therapeutic target for atherosclerosis-related diseases.