Tumor Necrosis Factor-related Protein Research Articles

Dynamics of Gill Responses to a Natural Infection with Neoparamoeba perurans in Farmed Tasmanian Atlantic Salmon.

Gill health has become a significant global challenge for Atlantic salmon (Salmo salar) aquaculture, particularly during the marine phase of farming. The increasing prevalence of gill pathologies has been linked to rising seawater temperatures, underscoring the need to evaluate existing tools for monitoring gill health and to develop novel approaches for early detection. In this study, we investigated the gill responses of commercially farmed Atlantic salmon to natural infection with Neoparamoeba perurans during an outbreak of amoebic gill disease (AGD) in Tasmania. Our focus spanned the low AGD prevalence, high AGD prevalence, and post-freshwater treatment stages of the outbreak. Evaluations of gill tissue included assessments of the gross AGD score, histopathological score, abundance of N. perurans (measured by 18S rRNA gene expression), and expression levels of inflammation-related transcripts. We demonstrated a strong correlation between different measures of AGD-related gill pathology and significant differences between distinct stages of the N. perurans outbreak. Post-treatment, fish exhibited considerable variability in their responses to the freshwater bath, highlighting the necessity for personalized management strategies that consider genetic, environmental, and health status factors. The expression patterns of angiogenin-1 (ANG1) and complement C1q tumour necrosis factor-related protein 3-like (C1QTNF3) emphasize their potential as biomarkers for early detection of gill damage in salmon aquaculture worldwide.

Decreased Serum CTRP3 level was associated with connective tissue diseases

ObjectiveComplement C1q tumor necrosis factor-related protein 3 (CTRP3) and 9 (CTRP9) are two of the most extensively studied adipokines, known for their diverse biological functions. However, it remains unclear whether serum levels of CTRP3 or CTRP9 are associated with connective tissue diseases (CTD). MethodsSerum CTRP3 and CTRP9 levels were measured by enzyme-linked immune sorbent assay (ELISA) and analyzed in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjogren's syndrome (pSS), ankylosing spondylitis (AS), undifferentiated connective tissue disease (UCTD), as well as in healthy controls (HCs). ResultsSerum CTRP3 levels were all significantly lower in patients with RA, SLE, pSS and AS compared with HCs. However, there were no significant differences in serum CTRP9 levels between patients with RA, SLE, pSS, or AS and HCs. In pSS patients, CTRP3 showed a weak correlation with blood glucose, creatinine, and urine acid in pSS patients, while no correlations were observed between serum CTRP3 levels and clinical or laboratory indices in RA, SLE or AS patients. Stable associations between CTRP3 and RA, SLE, pSS and AS were evaluated using multivariate logistics regression analysis. Receiver operating characteristic (ROC) curves were plotted to evaluated CTRP3 as a marker for RA, SLE, pSS and AS, yielding area under curve (AUC) values of 0.691, 0.727, 0.658 and 0.694, respectively. ConclusionDecreased serum CTRP3 levels were associated with RA, SLE, pSS and AS.

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.

Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept: a quantitative analysis based on 4D label-free technique.

To identify different metabolites, proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy (PDR) and resistance to anti-vascular endothelial growth factor (VEGF) drugs, and to provide biomarkers for the diagnosis and treatment of PDR. Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS/MS) analyses based on 4D label-free technology. Statistically differentially expressed proteins (DEPs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representation and protein interactions were analyzed. A total of 12 samples were analyzed. The proteomics results showed that a total of 58 proteins were identified as DEPs, of which 47 proteins were up-regulated and 11 proteins were down-regulated. We found that C1q and tumor necrosis factor related protein 5 (C1QTNF5), Clusterin (CLU), tissue inhibitor of metal protease 1 (TIMP1) and signal regulatory protein alpha (SIRPα) can all be specifically regulated after aflibercept treatment. GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR. In addition, protein-protein interaction (PPI) network evaluation revealed that TIMP1 plays a central role in neural regulation. In addition, CD47/SIRPα may become a key target to resolve anti-VEGF drug resistance in PDR. Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR. Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept, among which C1QTNF5, CLU, TIMP1 and SIRPα may become targets for future treatment of PDR and resolution of anti-VEGF resistance.

Transcriptomic analysis of GITR and GITR ligand reveals cancer immune heterogeneity with implications for GITR targeting.

Glucocorticoid-induced tumor necrosis factor related protein (GITR) is a transmembrane protein expressed mostly on CD25+CD4+ regulatory T-cells (Tregs) and upregulated on all T-cells upon activation. It is a T-cell co-stimulatory receptor and has demonstrated promising anti-tumor activity in pre-clinical studies. To date, however, the efficacy of GITR agonism has been discouraging in clinical trials. This study explores GITR and GITR ligand (GITR-L) ribonucleic acid (RNA) expression in solid tumors in an attempt to delineate causes for variable responses to GITR agonists. RNA expression levels of 514 patients with a variety of cancer types were normalized to internal housekeeping gene profiles and ranked as percentiles. 99/514 patients (19.3%) had high GITR expression (defined as ≥ 75th percentile). Breast and lung cancer had the highest proportion of patients with high GITR expression (39% and 35%, respectively). The expression of concomitant high GITR and low-moderate GITR-L expression (defined as <75th percentile) was present in 31% and 30% of patients with breast and lung cancer respectively. High GITR expression also showed a significant independent association with high RNA expression of other immune modulator proteins, namely, PD-L1 immunohistochemistry (IHC) ≥1 (odds ratio (OR) 2.15, P=0.008), CTLA4 (OR=2.17, P=0.05) and OX40 high RNA expression (OR=2.64, P=0.001). Overall, these results suggest that breast and lung cancer have a high proportion of patients with a GITR and GITR-L RNA expression profile that merits further investigation in GITR agonism studies. The association of high GITR expression with high CTLA4 and OX40 RNA expression, as well as positive PD-L1 IHC, provides a rationale for a combination approach targeting these specific immune modulator proteins in patients whose tumors show such co-expression.

#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&lt; 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]&gt;1 and p&lt; 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]&lt;1 and p&lt; 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.

GITR activation ex vivo impairs CD8 T cell function in people with HIV on antiretroviral therapy

Glucocorticoid-induced tumor necrosis factor related protein (GITR) is a co-stimulatory immune checkpoint molecule constitutively expressed on regulatory Tcells (Tregs) and on activated T conventional cells (Tconv). In blood collected from PWH on suppressive ART, GITR expression was reduced in multiple activated CD4 and CD8 Tcell subsets but was increased in Tregs. HIV specific CD8 Tcells expressed higher levels of GITR and programmed cell death protein 1 (PD-1) compared to total CD8 Tcells. Following stimulation with HIV peptides and GITR-ligand (L), we demonstrated a significant decrease in killing by HIV specific CD8 Tcells and an increased exhausted profile. Tcell receptor co-stimulation with GITR-L abrogated Treg suppression and induced expansion of CD4 Tconv. We conclude that GITR activation is an additional factor contributing to an impaired HIV immune response in PWH on ART and that GITR agonist antibodies should not be pursued for HIV cure strategies.

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.

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.

The clinical significance of serum complement component 1q tumor necrosis factor-related protein 3 and complement component 1q tumor necrosis factor-related protein 9 levels in patients with rheumatoid arthritis

Objective: The objective of this study was to assess the expression of serum complement component 1q tumor necrosis factor-related protein 3 (CTRP3) and CTRP9 in rheumatoid arthritis (RA) patients, and further explore their correlation with disease activity and the predictive value of RA. Methods: RA group (n = 60) and healthy group (n = 60) were enrolled in Beijing Luhe Hospital, Capital Medical University. We collected the clinical data, including the basic information, laboratory parameters as well as the Disease Activity Score using 28 joint counts (DAS28) scores, and measured the expression of serum CTRP3 and CTRP9 in two groups by enzyme-linked immunosorbent assay. To analyze the correlation between serum CTRP3 and CTRP9 and RA. We explored the predictive value of the serum CTRP3 and CTRP9 for RA. Results: Compared to the healthy group, the expression of serum CTRP3 and CTRP9 was higher in the RA group (P &lt; 0.05). Except rheumatoid factor (serum CTRP9: r = −0.310, P = 0.018), and immunoglobulin (serum CTRP9: r = 0.338, P = 0.010), platelet, erythrocyte sedimentation rate, C-reactive protein, DAS28, anti-cyclic citrullinated peptide antibody, triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, etc., of RA patients were not related to the levels of serum CTRP3 and CTRP9. The best cutoff value of serum CTRP3 and CTRP9 was 31.66 and 34.39 ng/ml, respectively. In terms of sensitivity, negative predictive value, and accuracy, compared with single detection of serum CTRP3 or CTRP9, combined detection has more predictive value for RA. Conclusion: CTRP3 and CTRP9 may become two candidate biomarkers for RA. The serum CTRP3 and CTRP9 may have certain predictive values for RA.

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.

Ellagic acid ameliorates high fructose-induced hyperuricemia and non-alcoholic fatty liver in Wistar rats: Focusing on the role of C1q/tumor necrosis factor-related protein-3 and ATP citrate lyase

AimsHigh-fructose intake (HF) represents an inducible risk factor for non-alcoholic fatty liver disease (NAFLD). Present study aimed to illustrate the effect of HF diet (HFD) on the induction of NAFLD, hyperuricemia and role of ellagic acid as modulator. Main methodsTwenty-four adult male albino rats were randomly divided into four groups (6/each). The first group received normal chow diet only while the others received 60 % HFD for 4 weeks and subdivided later into 3 groups. The first and second groups received allopurinol and ellagic acid, respectively while the third group received HFD only for extra 4 weeks. Key findingsRats fed on HFD for 8 weeks displayed body weight gain, insulin resistance (IR), hyperglycemia, dyslipidemia, hyperuricemia with increased oxidative stress and hepatic lipogenic enzymes such as ATP citrate lyase (ACL), aldolase B, and fatty acid synthase (FAS), sterol regulatory element-binding protein 1 (SERBP-1c). C1q /tumor necrosis factor-related protein −3 (CTRP3), and phosphorylated AMP-activated protein kinase (p-AMPK) however showed significant decreases. Ellagic acid or allopurinol administration significantly decreased serum lipids, uric acid, glucose, insulin levels and hepatic contents of enzymes. Malondialdehyde (MDA), FAS, aldolase B, SERBP-1c, and xanthine oxidase (XO) hepatic contents showed significant decreases along with glutathione (GSH) increase as compared to fructose group where ellagic acid was more remarkable compared with allopurinol. SignificanceOur findings indicated that ellagic acid had alleviated HFD-induced hyperuricemia, its associated NAFLD pattern as mediated through activation of CTRP3 and inhibition of ACL activities in a pattern more remarkable than allopurinol.

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.

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.

TRAIL Therapy for Breast Cancer Treatment by Employing Lipopolymer mRNA Delivery

Promising improvements in synthesis of stable and nonimmunogenic messenger RNA (mRNA) have enhanced the potential for mRNA in in situ production of therapeutic proteins. In this study, we explored the delivery of an mRNA expressing the tumor necrosis factor-related apoptosis-inducing ligand protein (mTRAIL) into breast cancer cells and human bone marrow stromal cells (hBMSCs) by using aliphatic lipid-modified small molecular weight polyethylenimine (PEI) carriers. The duration and extent of TRAIL secretion after mRNA delivery were dependent on the cell type, but mRNA delivery consistently showed earlier and higher protein expression compared with plasmid DNA delivery. Higher TRAIL-induced cytotoxicity and apoptosis induction were evident in breast cancer cells after mTRAIL transfection. In addition, hBMSCs transfected with mTRAIL were able to effectively kill breast cancer cells after coculture. mTRAIL delivery with the lipopolymers resulted in significant inhibition of breast cancer tumor growth in a xenograft model in mice. We conclude that an mRNA-based approach to TRAIL expression is a highly promising approach to retard the growth of breast cancer cells.