Lipid-lowering medications and risk of malignant melanoma: a Mendelian randomization study.

Background: The relationship between blood lipids, lipid-modifying medications, and cancer risk has been under investigation for some time. Recent studies suggest that lipid-lowering medications might influence melanoma outcomes, though findings remain controversial. Our study aims to clarify the potential causal relationship between lipid-lowering drugs commonly used and melanoma incidence through a comprehensive Mendelian randomization (MR) analysis. Methods: Genetic variations within an LDL-related drug target gene (LDL-cholesterol from a genome-wide association study) served as proxies for exposure to lipid-lowering drugs. We conducted a two-sample Mendelian randomization analysis using inverse variance weighting (IVW), MR-Egger, and weighted median approaches. The MR-PRESSO test and pleiotropy_test were utilized to identify and adjust for horizontal pleiotropy. Stability and reliability of the Mendelian randomization findings were assessed using the leave-one-out method, Cochran's Q test, and funnel plot analysis. Odds ratios (OR) were employed to evaluate the causal relationship between genetic proxies of lipid-lowering drugs and melanoma risk. Results: IVW analysis revealed that HMGCR gene expression is linked to a decreased risk of melanoma [OR: 0.624(0.439-0.888); p = 0.008]. Conversely, PCSK9 gene expression is tied to an elevated risk of melanoma [OR: 1.233(1.026-1.484); p = 0.025]. No significant association was observed between NPC1L1 and melanoma. Conclusions: HMGCR inhibitors (statins) may increase melanoma risk, while PCSK9 inhibitors (evolocumab, alirocumab) could potentially decrease melanoma risk.

Circular RNA hsa_circ_0011298 enhances Taxol resistance of non-small cell lung cancer by regulating miR-486-3p/CRABP2 axis.

BACKGROUND: Circular RNAs (circRNAs) serve as critical regulators in the chemoresistance of human cancers, including non-small cell lung cancer (NSCLC). We aimed to explore the role of hsa_circ_0011298 (circ_0011298) and its mechanism in Taxol resistance of NSCLC. METHODS: Circ_0011298, microRNA-486-3p (miR-486-3p), and CRABP2 mRNA expression were determined using qRT-PCR. EdU and MTT assays were used to detect cell proliferation. Cell cycle distribution and cell apoptosis were detected by flow cytometry. Cell migratory and invasive abilities were detected using transwell assay. Cellular glycolysis was determined by specific kits. Protein levels were examined by western blot. Dual-luciferase reporter and RIP assays were performed to confirm the relationship between miR-486-3p and circ_0011298 or CRABP2. Xenograft mice model was established to confirm the function of circ_0011298 in vivo. RESULTS: Circ_0011298 was overexpressed in Taxol-resistant NSCLC cells and tissues. Circ_0011298 knockdown enhanced Taxol sensitivity by decreasing cell proliferation, migration, invasion, and glycolysis and inducing apoptosis and cell cycle arrest in Taxol-resistant NSCLC cells. Circ_0011298 was a sponge of miR-486-3p, and the impact of circ_0011298 silencing on Taxol resistance was rescued by miR-486-3p inhibition. Moreover, miR-486-3p directly targeted CRABP2, and miR-486-3p inhibited Taxol resistance by targeting CRABP2. Furthermore, circ_0011298 regulated CRABP2 expression through targeting miR-486-3p. Importantly, circ_0011298 interference elevated Taxol sensitivity of NSCLC in vivo. CONCLUSION: Circ_0011298 elevated Taxol resistance of NSCLC by sponging miR-486-3p and upregulating CRABP2, providing a possible circRNA-targeted therapy for NSCLC.

Efficacy of Autologous Bone Marrow Mononuclear Cell Transplantation Therapy for Type 2 Diabetes Mellitus: An Updated Meta-Analysis.

INTRODUCTION: Studies of the effects of stem cell therapy on type 2 diabetes mellitus (T2DM) have not reached consistent results. Our meta-analysis aimed to systematically evaluate the efficacy of autologous bone marrow-derived stem cells (ABM-MNCs) on T2DM. METHODS: We systematically searched PubMed, EMBASE, Web of Science, and the Cochrane Library for studies published between 1980 and May 2018. Two researchers screened the literature independently following the inclusion and exclusion criteria. Meta-analysis of the pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated based on either a fixed- or random-effects model. RESULTS: We identified six studies with 206 participants investigating the effects of autologous bone marrow stem cell therapy on T2DM after screening 102 studies found after the initial search. According to the pooled estimates, compared with the control group, after 12-month follow-up the ABM-MNC therapy group had a lower level of HbA1c (MD, - 1.18; 95% CI, - 1.40 to 0.95) and lower required insulin dose (MD, - 2.05; 95% CI, - 3.55 to - 0.55). HbA1c decreased after ABM-MNC therapy compared with before (12 months: MD, - 1.22; 95% CI, - 1.43 to - 1.0). We also observed a significant decrease in insulin requirement after 3-, 6-, 9-, and 12-month follow-up in the ABM-MNC group, respectively. CONCLUSION: Autologous stem cell therapy showed a beneficial effect on T2DM.

Association between interleukin 37 (rs3811047) polymorphism and multiple autoimmune diseases in a Chinese population: A PRISMA-compliant meta-analysis.

OBJECTIVE: Emerging evidence suggests that interleukin 37 (IL-37) plays an important role in the pathogenesis of several autoimmune diseases (ADs), but the correlations are still unclear. We conducted a meta-analysis to explore whether IL-37 gene (rs3811047) polymorphism was associated with susceptibility to multiple ADs in a Chinese population. METHODS: Relevant studies were searched in the PubMed, Embase, Chinese National Knowledge Infrastructure, and Chinese Wangfang databases up to August 31, 2017. Odds ratio (OR) and its 95% confidence interval (95% CI) was used to estimate the strength of the association in different genetic models. The results of fixed or random models were adopted according to the heterogeneity. Publication bias and sensitive analysis were also performed to evaluate the reliability of results. RESULTS: A total of 3161 patients and 4078 controls from 6 studies were included in this meta-analysis. Pooling all data together, a significant association between IL-37 gene (rs3811047 A/G) polymorphism and susceptibility to ADs in the Chinese population was found in all 4 genetic models (allelic model A vs G: OR = 0.73 95% CI = 0.67∼0.79; recessive model AA + AG vs GG: OR = 0.72, 95% CI = 0.65∼0.79; dominant model AA vs AG + GG: OR = 0.59, 95% CI = 0.45∼0.77; homozygous model AA vs GG: OR = 0.55, 95% CI = 0.42∼0.72). No heterogeneity and publication bias was detected in all models. Sensitive analysis indicated that all of the positive results are reliable. CONCLUSION: The IL- 37 (rs3811047) polymorphism contributes to the development of ADs in a Chinese population.