Multi-faceted roles of C1q/TNF-related proteins family in atherosclerosis.

Purpose of review: C1q/TNF-related proteins (CTRPs) are involved in the modulation of the development and prognosis of atherosclerosis (AS). Here, we summarizes the pathophysiological roles of individual members of the CTRP superfamily in the development of AS. Currently, there is no specific efficacious treatment for AS-related diseases, therefore it is urgent to develop novel therapeutic strategies aiming to target key molecules involved in AS. Recent findings: Recently, mounting studies verified the critical roles of the CTRP family, including CTRP1-7, CTRP9 and CTRP11-15, in the development and progression of AS by influencing inflammatory response, modulating glucose and lipid metabolism, regulating endothelial functions and the proliferation of vascular smooth muscle cells (VSMCs). Conclusions: CTRP family regulate different pathophysiology stages of AS. CTRP3, CTRP9, CTRP12, CTRP13 and CTRP15 play a clear protective role in AS, while CTRP5 and CTRP7 play a pro-atherosclerotic role in AS. The remarkable progress in our understanding of CTRPs' role in AS will provide an attractive therapeutic target for AS.

Association between iron status and incident coronary artery disease: a population based-cohort study.

Disorders of iron metabolism has been implicated in cardiovascular disease. However, the association of serum iron stores and coronary artery disease (CAD) remains inconsistent. Here, we investigated the associations of serum iron metabolism with the incidence of CAD, the severity of coronary artery stenosis, metabolic biomarkers, and the risk of major adverse cardiovascular event (MACE). A total of 643 CAD patients and 643 healthy controls were enrolled to assess the associations of serum iron status with the presence of CAD, the severity of CAD, and the risk of MACE. Serum iron metabolism and other metabolic markers were measured in all subjects. All statistical analyses were analyzed using SPSS22.0 software and STATA statistical package. Serum level of iron metabolism markers, including serum iron, unsaturated transferrin iron binding capacity (UIBC), Total iron binding capacity (TIBC) levels, in CAD groups was significantly lower than the control group (P < 0.001). UIBC and TIBC were negatively correlated with ferritin in both sexes. Each unit increase of serum iron and TIBC were found to have a protective role for CAD in women (iron: OR 0.794, 95% CI (0.647-0.973), TIBC: OR 0.891, 95% CI (0.795-0.999), P < 0.05). However, high ferritin level was significant associated the CAD incident in both sexes (OR 1.029, 95% CI (1.002-1.058) in men, OR 1.013, 95% CI (1.0-1.025) in women, P < 0.05). Serum iron metabolism markers exhibited no significant association with the severity of CAD. Increased serum level of iron and TIBC levels were found to have a protective role for CAD in women, but not in men. Elevated serum ferritin is independently and positively associated with CAD in men and women.

[Clinical study of heparin anticoagulation scheme during plasma adsorption therapy for liver failure].

Objective: To investigate the reasonable dosage of heparin anticoagulation scheme during plasma adsorption (PA) therapy for liver failure. Methods: Patients with liver failure treated with PA therapy were retrospectively collected and divided according to the anticoagulation scheme into the first-dose heparin anticoagulation group and the first-dose plus maintenance heparin anticoagulation group. Clinical data and laboratory test results were compared before and after treatment between the two groups. Paired t-tests were used for comparison within the normally distributed groups. An independent two-sample t-test was used for inter group comparison. Wilcoxon rank-sum test was used for measurement data that did not conform to a normal distribution. Fisher's exact test was used to compare the count data between groups. Results: There were 138 cases with liver failure treated with PA therapy from October 2017 to September 2020. Among them, 83 and 55 cases were in the first-dose heparin anticoagulation and first-dose plus maintenance heparin anticoagulation group, respectively. Age, gender, and laboratory data before treatment were comparable between the two groups. PA treatment was successfully completed in both groups of patient, and there was no statistically significant difference in the determination of coagulation level with plasma separators (Z=-0.15, P=0.216). There were different degrees of bleeding complications in both groups. In the first-dose heparin anticoagulation group, there were two cases (2.4%) of central venous catheter bleeding and one case (1.2%) of epistaxis. In the first-dose plus maintenance heparin anticoagulation group, there were five cases (9.1%) of central venous catheter bleeding, two cases (3.6%) of skin bleeding, one case (1.8%) of epistaxis, and one case (1.8%) of upper gastrointestinal bleeding. The incidence of bleeding complications was lower in the first-dose of heparin anticoagulation than first-dose plus maintenance heparin anticoagulation group, and the difference was statistically significant (P<0.001). The activated partial thromboplastin time of the two groups was prolonged after therapy withdrawal than with therapy, and the difference was statistically significant (first-dose heparin anticoagulation group: t=3.850, P=0.022; first-dose plus maintenance heparin anticoagulation group: t=6.733, P=0.007). The activated partial thromboplastin time was prolonged in patients with first-dose plus maintenance heparin anticoagulation than first-dose heparin anticoagulation group, and the difference was statistically significant (P=0.025). The total bilirubin of the two groups before and after PA was significantly changed (the first-dose heparin anticoagulation group: Z=-2.455, P=0.017; the first-dose plus maintenance heparin anticoagulation group: Z=-2.307, P=0.024), and there was no statistically significant difference between the two groups (P=0.412). There was no statistically significant difference in platelet changes before and after PA therapy between the two groups (the first dose of heparin anticoagulation group: Z=-0.529, P=0.480; the first-dose plus maintenance heparin anticoagulation group: Z=-0.276, P=0.362). Conclusion: Anticoagulation scheme without maintenance medication is feasible with prothrombin activity before ≤20-40%, activated partial thromboplastin time of ≤87 s (2 times the upper normal value), platelet count before treatment (excluding contraindications to heparin) ≥50×109/L, and the first dose of heparin administration of 0.2 mg/kg during PA therapy in patients with liver failure.

Serum Complement C1q Activity Is Associated With Obstructive Coronary Artery Disease.

Background: Complement C1q plays a dual role in the atherosclerosis. Previous studies showed inconsistent results about the association of serum C1q levels and coronary artery disease (CAD). Here, we explored the associations of serum C1q activity with CAD, coronary stenosis severity, cardiovascular biomarkers, and 1-year restenosis after coronary artery revascularization. Methods: We enrolled 956 CAD patients and 677 controls to evaluate the associations of serum complement C1q activity to the presence and severity of obstructive CAD and non-obstructive CAD. Serum C1q activity and the concentrations of laboratory markers were measured in all subjects. All the data were analyzed using SPSS22.0 software. Results: Serum C1q activity in Obstructive CAD and Non-Obstructive CAD groups was significantly higher than the control group (195.52 ± 48.31 kU/L and 195.42 ± 51.25 kU/L vs. 183.44 ± 31.75 kU/L, P < 0.05). Greater C1q activity was significantly correlated with higher total cholesterol (TC) and triglyceride (TG) levels. C1q activity was associated with an increased Odds Ratio (OR) of CAD (OR = 1.322, 95% CI 1.168-1.496, P < 0.05) and 1-year restenosis after revascularization (the highest OR = 3.544, 95% CI 1.089-12.702, P < 0.05). Complement C1q activity was not correlated with Gensini score in the Obstructive CAD group after adjustment for confounders. C1q activity has low value in predicting the incidence of CAD. Conclusion: Serum complement C1q activity is associated with obstructive CAD.

Circ-XPR1 promotes osteosarcoma proliferation through regulating the miR-214-5p/DDX5 axis.

Circular RNAs (circRNAs) are a new class of RNAs that play an important role in the development of various tumors. However, the expression profile and biological function of circRNAs in osteosarcoma (OS) progression remain unclear. OS-related circRNA expression profiles from the GEO database (GSE96964) were downloaded to identify differentially expressed circRNAs between OS and normal tissues. We identified one upregulated circRNA (Circ-XPR1), and RT-PCR was performed to further confirm the expression abundance in OS tissue. Circ-XPR1 was closely related to overall survival and disease-free survival of OS patients. Knockdown of Circ-XPR1 significantly reduced the proliferation of OS cells. Gain- and loss-of-function studies showed that Circ-XPR1 promoted OS cell proliferation by sponging miR-214-5p to regulate DDX5 expression. Our findings suggested that Circ-XPR1 regulates OS cell proliferation by sponging miR-214-5p to regulate DDX5 expression. Therefore, the Circ-XPR1/miR-214-5p/DDX5 axis may serve as a potential therapeutically relevant target for OS.

Changes of liver transcriptome profiles following oxidative stress in streptozotocin-induced diabetes in mice.

BACKGROUND: Oxidative-stress (OS) was causal in the development of cell dysfunction and insulin resistance. Streptozotocin (STZ) was an alkylation agent that increased reactive oxygen species (ROS) levels. Here we aimed to explore the oxidative-stress and related RNAs in the liver of STZ-induced diabetic mice. METHODS: RNA-sequencing was performed using liver tissues from STZ induced diabetic mice and controls. Pathway and Gene Ontology (GO) analyses were utilized to annotate the target genes. The differentially expressed RNAs involved in the peroxisome pathway were validated by qRT-PCR. The glucose metabolite and OS markers were measured in the normal control (NC) and STZ-induced diabetic mellitus (DM) group. RESULTS: The levels of serum Fasting insulin, HbA1c, Malondialdehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α) were significant higher in DM groups than NC group, while SOD activity decreased significantly in DM groups. We found 416 lncRNAs and 910 mRNAs were differentially expressed in the STZ-induced diabetic mice compared to the control group. OS associated RNAs were differentially expressed in the liver of STZ-induced diabetic mice. CONCLUSION: This study confirmed that the OS was increased in the STZ-induced DM mice as evidenced by the increase of lipid peroxidation product MDA and 8-iso-PGF2α, identified aberrantly expressed lncRNAs and mRNAs in STZ-induced diabetic mice.

Long Non-Coding RNA TUG1 Modulates Proliferation, Migration, And Invasion Of Acute Myeloid Leukemia Cells Via Regulating miR-370-3p/MAPK1/ERK.

BACKGROUND: Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Long non-coding RNA taurine-upregulated gene 1 (lncRNA TUG1) has been discovered to participate in multiple cancers including AML. However, the detailed mechanism of TUG1 in AML remains obscure. MATERIALS AND METHODS: AML cell lines HL-60 and Kasumi-1 were taken as cell models. TUG1 knockdown or overexpression cell lines were generated. Then, the biological influence of TUG1 on cancer cells was studied using CCK-8 assay, transwell assay and Western blot in vitro. Interaction between TUG1 and miR-370-3p was determined by bioinformatics analysis, RT-PCR, and luciferase assay. Western blot, RT-PCR, and luciferase assay were carried out to validate the interaction between miR-370-3p and its target gene Mitogen-Activated Protein Kinase 1 (MAPK1). RESULTS: Knockdown of TUG1 markedly reduced viability and metastasis of AML cells, while its overexpression had the opposite effect. MAPK1 was verified as a target gene of miR-370-3p. TUG1 could reduce the level of functional miR-370-3p, facilitate MAPK1 expression, and in turn activate ERK1/2 signaling. CONCLUSION: TUG1 could modulate malignant phenotypes of AML cells via miR-370-3p/MAPK1/ERK signaling. Our study would help to clarify the mechanism of AML tumorigenesis and progression.

The moderate predictive value of serial serum CRP and PCT levels for the prognosis of hospitalized community-acquired pneumonia.

BACKGROUND: To predict the prognosis by observing the dynamic change of C-reactive protein (CRP) and procalcitonin (PCT) for hospitalized community-acquired pneumonia (CAP). METHODS: The data were collected from January to December 2017 from the first affiliated Hospital of Zhengzhou University. Demographic and clinical patient information including age, length of hospital stay and Charlson Comorbidity Index (CCI) were recorded. Blood samples were taken for CRP, PCT, and white blood cell count (WBC). Receiver Operating Characteristic (ROC) curve was used to verify each biomarker's association with the prognosis of pneumonia. RESULTS: A total of 350 patients were enrolled in the study. The 30-day mortality was 10.86%. Serial serum CRP3, CRP5, PCT3, PCT5 and PCT5c levels were statistically lower in CAP survivors than non-survivors. CRP3c < 0, CRP5c < 0 and PCT5c < 0 were observed with a statistically lower frequency in patients with 30-day mortality and initial treatment failure. The AUC for 30-day mortality for serial CRP levels combined with CRP clearances was 0.85 (95% CI 0.77-0.92), as compared to an AUC of 0.81 (95% CI 0.73-0.9) for serial PCT levels combined with PCT clearances. CONCLUSIONS: Serum serial CRP and PCT levels had moderate predictive value for hospitalized CAP prognosis. The dynamic CRP and PCT changes may potentially be used in the future to predict hospitalized CAP prognosis.

The association between TNFR gene polymorphisms and the risk of Hepatitis B Virus-Related Liver Diseases in Chinese population.

Tumor necrosis factor receptor superfamily 2 (TNFR2) plays an important role in controlling the progression of antiviral and antitumorr. Evidence suggests that TNFR2 is involved in the pathogenesis of HBV-induced liver injury. We therefore examined whether TNFR2 polymorphisms are associated with the risk of HBV-related liver disease in Chinese population. In this case-control study, 115 chronic hepatitis B (CHB) patients, 86 HBV-related liver cirrhosis patients (LC), 272 HBV-related hepatocellular carcinoma patients (HCC) and 269 healthy controls were recruited. TNFR2 rs1061622 and rs1061624 polymorphisms were examined using a polymerase chain reaction-restriction fragment length polymorphism analysis. Binary logistic regression analyses revealed that the A allele of rs1061624 was positively associated with the risk of CHB (AA vs. GG, P = 0.026; AA vs. GA+GG, P = 0.021), LC (AA vs. GG, P = 0.027; AA+GA vs. GG, P = 0.036), and HCC (GA vs. GG, P = 0.046; GA+AA vs. GG, P = 0.031). Moreover, subgroup analysis indicated that male subjects have increased risk in developing CHB and LC. Nevertheless, no association was found between rs1061622 polymorphism and HBV-related liver diseases in the overall or subgroup analyses. Our retrospective study suggests that the TNFR2 rs1061624 polymorphism is associated with HBV-related CHB, LC, and HCC in Chinese population, particularly in males.

XRCC1 Arg399Gln polymorphism is not associated with breast cancer in Chinese.

BACKGROUND: A number of studies have been conducted to explore the association of XRCC1 polymorphisms with Breast cancer (BC) risk in Asians, but the results have been inconsistent. We therefore performed the present meta-analysis to explore the relationship in detail. MATERIALS AND METHODS: Reported studies were searched from 1990 to October 15, 2014 in PubMed and Wan fang Med Online. We performed a meta-analysis of 13 published case-control studies fitting our eligibility criteria. These studies involved XRCC1 Arg399Gln polymorphisms in 4984 BC cases and 5744 controls in dominant (ArgArg vs. GlnGln+ArgGln), recessive (ArgGln+ArgArg vs. GlnGln), and co-dominant (ArgArg vs. GlnGln) inheritance models. The total odds Ratio (OR) and 95% CI were calculated and analyzed by Review Manager 5.2 and STATE 12. RESULTS: Overall, significantly increased BC risk was observed in any genetic model (dominant model: odds ration [OR] = 1.31, 95% confidence interval [CI] = [1.08, 1.58]; recessive model: OR = 0.63, 95% CI = [0.50, 0.81]; codominant model: OR = 2.52, 95% CI: [1.38, 4.60]) when all eligible studies were pooled into the meta-analysis. In further stratified analyses, no association was found between Arg399Gln polymorphism and BC risk in Chinese fewer than three hereditary models. CONCLUSIONS: Our results suggest that the XRCC1 Arg399Gln polymorphism may be associated with increased Breast cancer risk among Asians, except Chinese population.

Activin A supplement in the hESCs culture enhances the endoderm differentiation efficiency.

Activin A is a critical regulator in human embryonic stem cells (hESCs) maintenance and differentiation. Different concentrations of Activin A affect hESC maintenance and differentiation in different ways. A high concentration favors anterior primitive streak and gives rise to DE if the stimulation persists. hESCs were cultured with and without 10 ng/mL Activin A supplement respectively. The two groups of cells were differentiated into endoderm cells with 100 ng/mL Activin A and other reagents. Microarray-based DNA methylation was analyzed with the Infinium Human Methylation450 BeadChip on these two groups. There was a significant difference in endoderm differentiation efficiency (average efficiency: 71 vs. 58.5%, P < 0.05). hESCs cultured with Activin A supplement had an increased propensity to form definitive endoderm cells in response to Activin A and Wnt signal. Differentially Methylated Regions (DMRs) between these two groups were found. DMRs were related to the stem cell maintenance and gene regulation by peroxisome proliferators via PPARα, indicating that hESCs maintained with Activin A supplement had stronger "stemness."