Sarcopenia and gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation.

Objective: The aim of this study was to investigate the prevalence of sarcopenia (SP) and its relationship with gut microbiota alterations in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT). Methods: A total of 108 patients with various hematological disorders were selected from Peking University People's Hospital. SP was screened and diagnosed based on the 2019 Asian Sarcopenia Diagnosis Strategy. Physical measurements and fecal samples were collected, and 16S rRNA gene sequencing was conducted. Alpha and beta diversity analyses were performed to evaluate gut microbiota composition and diversity. Results: After HSCT, significant decreases in calf circumference and body mass index (BMI) were observed, accompanied by a decline in physical function. Gut microbiota analyses revealed significant differences in the relative abundance of Enterococcus, Bacteroides, Blautia and Dorea species before and after HSCT (P<0.05). Before HSCT, sarcopenic patients had lower Dorea levels and higher Phascolarctobacterium levels than non-sarcopenia patients (P<0.01). After HSCT, no significant differences in species abundance were observed. Alpha diversity analysis showed significant differences in species diversity among the groups, with the highest diversity in the post-HSCT 90-day group and the lowest in the post-HSCT 30-day group. Beta diversity analysis revealed significant differences in species composition between pre- and post-HSCT time points but not between SP groups. Linear discriminant analysis effect size (LEfSe) identified Alistipes, Rikenellaceae, Alistipes putredinis, Prevotellaceae defectiva and Blautia coccoides as biomarkers for the pre-HSCT sarcopenia group. Functional predictions showed significant differences in anaerobic, biofilm-forming and oxidative stress-tolerant functions among the groups (P<0.05). Conclusions: This study demonstrated a significant decline in physical function after HSCT and identified potential gut microbiota biomarkers and functional alterations associated with SP in patients with hematological disorders. Further research is needed to explore the underlying mechanisms and potential therapeutic targets.

miR-206 Inhibits Cell Proliferation and Extracellular Matrix Accumulation by Targeting Hypoxia-Inducible Factor 1-alpha (HIF-1α) in Mesangial Cells Treated with High Glucose.

BACKGROUND The goal of this study was to investigate the expression of miR-206 in human glomerular mesangial cells (hMCs) treated by exposure to high glucose (HG) levels, to assess the influence of miR-206 on the proliferation and extracellular matrix (ECM) deposition of hMCs, and to investigate the potential mechanisms of action. MATERIAL AND METHODS The level of miR-206 was detected by RT-qPCR. MTT assay and colony formation assay were used to assess hMCs cell proliferation ability. Western blotting was carried out to measure the expression of related proteins. Bioinformatics software (http://www.targetscan.org) was used to predict the potential target genes of miR-206, and dual-luciferase reporter assay was used to confirm this prediction. RESULTS Our results suggest that the level of miR-206 was downregulated in HG-treated hMCs. Cell proliferation was promoted in HG-induced hMCs, while this phenomenon was significantly reversed with miR-206 mimics. miR-206 mimics significantly enhanced p21 expression and decreased cyclin D1 and CDK2 expressions, but the opposite was found in HG-induced hMCs. Moreover, the level of ECM proteins was notably increased in hMCs treated with HG, which was also significantly reversed by miR-206 mimics. miR-206 inhibitor had the opposite effects. Furthermore, HIF-1alpha was found to be a direct target of miR-206, and was negatively regulated by miR-206 in hMCs. miR-206 can target HIF-1alpha to modulate cell proliferation and ECM accumulation. CONCLUSIONS Collectively, our results suggest that miR-206 plays a vital role in HG-treated hMCs through inhibiting cell proliferation and ECM accumulation, partly via targeting HIF-1alpha.

Non-high-density lipoprotein cholesterol and risk of cardiovascular disease in the general population and patients with type 2 diabetes: A systematic review and meta-analysis.

AIMS: To examine the relationship of non-high-density lipoprotein cholesterol (non-HDL-C) level with cardiovascular disease (CVD) risk in type 2 diabetes patients and the general population by conducting a meta-analysis. METHODS: We made a comprehensive literature search for relevant observational studies investigating the relationship of non-HDL-C level with CVD risk in the general population and type 2 diabetes patients using the PubMed and Embase databases. Pooled risk ratio (RR) with 95% confidence intervals (CI) was calculated for the highest versus the reference lower non-HDL-Cl. RESULTS: A total of 13 studies with 156,381 individuals were included. The pooled RR of CVD was 1.59 (95% CI 1.46-1.72) in the general population and 1.99 (95% CI 1.57-2.51) in type 2 diabetes patients. Subgroup analysis showed the similar effect of non-HDL-C on CVD risk between men (RR1.98; 95% CI 1.70-2.30) and women (RR 1.63; 95% CI 1.35-1.96). However, elevated non-HDL-C was not associated with higher risk of cardiovascular mortality in the general population (RR 1.64; 95% CI 0.96-2.80) and type 2 diabetes patients (RR 1.08; 95% CI 0.57-2.07). CONCLUSIONS: Elevated non-HDL-C level is associated with an increased risk of CVD in the general population and type 2 diabetes patients.

miRNA­145 inhibits myocardial infarction­induced apoptosis through autophagy via Akt3/mTOR signaling pathway in vitro and in vivo.

The present study investigated the effects of micro (mi)RNA­145 on acute myocardial infarction (AMI) and the potential underlying mechanism. A total of 6 AMI and 6 normal rat tissues were investigated for the present study. It was demonstrated that miRNA­145 expression was downregulated in the AMI rat model, compared with the control group. Downregulation of miRNA­145 increased cardiac cell apoptosis, suppressed phosphorylated (p)­RAC­Î³ serine/threonine­protein kinase (Akt3) and p­mechanistic target of rapamycin (mTOR) protein expression levels and suppressed autophagy in an in vitro model of AMI. However, overexpression of miRNA­145 decreased cardiac cell apoptosis, induced p­Akt3 and p­mTOR protein expression and promoted autophagy in the in vitro model of AMI. The inhibition of Akt3 (GSK2110183, 1 nM) decreased the effect of the miRNA­145 upregulation on cell apoptosis in the in vitro model of AMI. Chloroquine diphosphate (5 µM) inhibited the regulatory effect of miRNA­145 upregulation on autophagy to adjust cell apoptosis, in the in vitro model of AMI. The results of the present study demonstrate that miRNA­145 inhibits myocardial infarction­induced apoptosis via autophagy associated with the Akt3/mTOR signaling pathway in vivo and in vitro.