Platelet-derived growth factor subunit-B mediating the effect of dickkopf-1 on acute myocardial infarction risk: a two-step Mendelian randomization study.

Previous studies have indicated a potential connection between plasma levels of Dickkopf-1 (DKK1) and platelet-derived growth factor subunit-B (PDGF-B) with the development of atherosclerosis. However, the causal relationship between DKK1, PDGF-B, and the risk of acute myocardial infarction (AMI) is yet to be established. To address this research gap, we conducted Mendelian randomization (MR) and mediation analyses to investigate the potential mediating role of PDGF-B in the association between DKK1 and AMI risk. Summary statistics for DKK1 (n = 3,301) and PDGF-B (n = 21,758) were obtained from the GWAS meta-analyses conducted by Sun et al. and Folkersen et al., respectively. Data on AMI cases (n = 3,927) and controls (n = 333,272) were retrieved from the UK Biobank study. Our findings revealed that genetic predisposition to DKK1 (odds ratio [OR]: 1.00208; 95% confidence interval [CI]: 1.00056-1.00361; P = 0.0072) and PDGF-B (OR: 1.00358; 95% CI: 1.00136-1.00581; P = 0.0015) was associated with an increased risk of AMI. Additionally, genetic predisposition to DKK1 (OR: 1.38389; 95% CI: 1.07066-1.78875; P = 0.0131) was linked to higher PDGF-B levels. Furthermore, our MR mediation analysis revealed that PDGF-B partially mediated the association between DKK1 and AMI risk, with 55.8% of the effect of genetically predicted DKK1 being mediated through genetically predicted PDGF-B. These findings suggest that genetic predisposition to DKK1 is positively correlated with the risk of AMI, and that PDGF-B partially mediates this association. Therefore, DKK1 and PDGF-B may serve as promising targets for the prevention and treatment of AMI.

Leptin and its receptor in glucose metabolism of T-cell lymphoma.

T-cell lymphoma (TCL) is a group of heterogeneous disorders with a poor response to conventional treatment. In order to identify novel therapeutic targets, the present study investigated the effect of leptin and its receptor on glucose metabolism in TCL. The expression of the leptin receptor (ObR), and glucose transporter (Glut)1 and 4 was detected in TCL and reactive lymphoid hyperplasia (RLH) tissues by immunohistochemical analysis. A higher level of ObR expression was observed in the TCL tissues than in the RLH tissues (58.3 vs. 22.2%; P=0.012), and ObR overexpression was associated with high expression of Glut1 (P=0.007). In vitro analysis using the human TCL MOLT-3 cell line demonstrated that leptin stimulated cell glucose uptake via promoting recruitment and expression of Glut1, effects which were abolished by ObR-specific small interfering RNA (siRNA). Additionally, MOLT-3 cell viability was also increased following leptin treatment. ObR-specific siRNA abolished these responses. In conclusion, these results suggested that leptin serves a critical role in TCL glucose uptake via the ObR.

Dietary Fat Consumption and Non-Hodgkin's Lymphoma Risk: A Meta-analysis.

OBJECTIVE: Many studies suggest that high-fat diets are linked to the etiology of non-Hodgkin's lymphoma (NHL). However, the findings are inconsistent and therefore the association between fat and non-Hodgkin's lymphoma remains unclear. In this study, we aim to quantitatively assess the association between fat consumption and the risk for NHL. METHODS: We reviewed 221 published cohort and case-control studies that reported relative risk (RRs) and corresponding 95% confidence intervals (CIs) of NHL and fat intake using PubMed, Cochrane, EMBASE, and Google Scholar databases. A random-effects model computed summary risk estimates. RESULTS: Based on our literature search, 10 of 221 studies (two cohort and eight case-control studies) were relevant to this meta-analysis. There was a significant association between total fat consumption and increased risk of NHL (RR = 1.26; 95% CI: 1.12-1.42); in addition, subgroup analysis showed a significant correlation with diffuse large B-cell lymphoma (RR = 1.41; 95% CI: 1.08-1.84) but not with follicular lymphoma (RR = 1.21; 95% CI: 0.97-1.52), small lymphocytic lymphoma/chronic lymphocytic leukemia (RR = 0.91; 95% CI: 0.68-1.23), nor with T cell lymphoma (RR = 1.12; 95% CI: 0.60-2.09). The funnel plot revealed no evidence for publication bias. CONCLUSION: Total fat consumption, particularly animal fat, increases the risk for NHL.

Meat intake and risk of inflammatory bowel disease: A meta-analysis.

BACKGROUND/AIMS: This meta-analysis is designed to determine the association between meat consumption and the risk of inflammatory bowel disease. MATERIALS AND METHODS: Search relevant literature published in PubMed, Cochrane before July 2015 without restrictions. Studies were included if relative ratios and the corresponding 95% confidence intervals of the risk of inflammatory bowel disease were reported with respect to meat consumption. RESULTS: Nine studies were included in this meta-analysis. Relative to those who did not or seldom eat meat, meat consumers had a significantly greater risk of inflammatory bowel disease (pooled relative ratio: 1.50, 95% confidence interval: 1.15-1.95). The funnel plot revealed no evidence for publication bias. CONCLUSION: Meat consumption may increase the risk of inflammatory bowel disease. Additional large prospective studies are warranted to verify this association.

Obesity and the risk of cholangiocarcinoma: a meta-analysis.

A number of studies have shown that obesity is implicated in the susceptibility to several cancers. However, the association between obesity and cholangiocarcinoma remains unclear. This meta-analysis aimed to quantitatively assess the association between overweight or obesity and the incidence of cholangiocarcinoma. A literature search was performed for cohort and case-control studies published from 1996 to 2013 using PubMed, Cochrane, and EMBASE databases. Studies were included if they reported odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) of cholangiocarcinoma with respect to obesity or overweight. Normal weight, overweight, and obesity were defined when the body mass index (BMI) was 18.5-24.9, 25-29.9, and ≥ 30 kg/m(2), respectively. Excess body weight was defined as BMI ≥ 25 kg/m(2). Ten studies met the inclusion criteria, which included five cohort and five case-control studies. Compared with normal weight, being overweight (pooled OR 1.30, 95 % CI 1.13-1.49), obesity (pooled OR 1.52, 95 % CI 1.13-1.89), and excess body weight (pooled OR 1.37, 95 %CI 1.22-1.55) were significantly associated with cholangiocarcinoma. The funnel plot revealed no evidence for publication bias. Obesity is associated with the increased risk of cholangiocarcinoma, which needs to be confirmed by long-term cohort studies.

[Pathophysiological characteristics of rat pulmonary hypertension and cor pulmonale induced by monocrotaline].

OBJECTIVE: To explore the mechanism of pulmonary hypertension and Cor Pulmonale rat models induced by monocrotaline (MCT). METHODS: Twenty Wistar male rats were randomly divided into normal control group and model group (n= 10), which received a single intraperitoneal injection of MCT solution (50 mg/kg , the first day) or dissolvant, respectively. On day 28 after MCT administration, the hemodynamic parameters were assessed; levels of tumour necrosis factor-alpha (TNF-alpha), nitric oxide (NO), endothelin-1 (ET-1), B-type natriuretic peptide(BNP) in pulmonary tissue or blood were measured using radio immunoassay or nitrate reductase method. RESULTS: 28 days after MCT injection, compared with control group, right ventricle systolic pressure (RVSP) increased and heart rate(HR), mean arterial pressure (MAP) decreased; Levels of TNF-alpha, NO, ET-1 in pulmonary tissue or blood increased significantly in MCT group. CONCLUSION: The potential mechanism of MCI- induced pulmonary hypertension and Cor Pulmonale rat models associates with increasing TNF-alpha, NO, ET-1 levels in vivo, which results from inflammatory injury of lung tissue and blood vessels induced by MCT.

[Preparation and primary analysis of monoclonal antibodies against VP5 protein of chicken infectious bursal disease virus].

Infectious bursal disease virus (IBDV), the causative agent of a highly contagious disease in chickens, carries a small nonstructural protein (NS). In this study, vvIBDV Gx-VP5 genes were cloned into plasmid pET30a( + ) and expressed in E. coli with IPTG inducing. BALB/c mice were immunized with the purified recombinant fusion protein. SP2/0 myeloma cells and spleen cells of BALB/c mice were fused by PEG(MW1500), three hybridoma cell lines were examined by indirect ELISA and clone for three times by limited dilution, and were named as 4B4, 6D12, 3E8. The subtype of the monoclonal antibodies were IgG1 with a subtype identified ELISA kit, and light chains were kappa. The ascites titers of monoclonal antibodies were 5 x 10(4), 3.5 x 10(4), 3 x 10(4) by indirect ELISA, respectively. Indirect ELISA and Western blot results showed that the monoclonal antibodies only acted with VP5 protein, IF analysis indicated that three monoclonal antibodies acted with IBDV Gt. There were specific fluorescence in detected Vero E6 cells which transient expressed VP5 protein by IFA. Therefore, monoclonal antibodies specific to IBDV VP5 proteins are specific method for detected VP5 proteins, and base on establish stabilize expressed VP5 protein Vero cell lines to research IBDV VP5 protein function.