Association between the gut microbiota and nonalcoholic fatty liver disease: A two-sample Mendelian randomization study.

BACKGROUND: Increasing studies have shown that there is a significant association between gut microbiota and non-alcoholic fatty liver disease. AIMS: To show the potential association between gut microbiota and non-alcoholic fatty liver disease, we performed a two-sample Mendelian randomization analysis. METHODS: We analyzed summary statistics from genome-wide association studies of gut microbiota and non-alcoholic fatty liver disease and conducted Mendelian randomization studies to evaluate relationships between these factors. RESULTS: Of the 211 gut microbiota taxa examined, the inverse variance weighted method identified Lactobacillaceae (OR = 0.83, 95% CI = 0.72 - 0.95, P = 0.007), Christensenellaceae (OR = 0.74, 95% CI = 0.59 - 0.92, P = 0.007), and Intestinibacter (OR = 0.85, 95% CI = 0.73 - 0.99, P = 0.035) were negatively correlated with non-alcoholic fatty liver disease. And Coriobacteriia (OR = 1.22, 95% CI = 1.01 - 1.42, P = 0.038), Actinomycetales (OR = 1.25, 95% CI = 1.02 - 1.53, P = 0.031), Oxalobacteraceae (OR = 1.10, 95% CI = 1.01 - 1.21, P = 0.036), Ruminococcaceae_UCG005 (OR = 1.18, 95% CI = 1.01 - 1.38, P = 0.033) are positively associated with non-alcoholic fatty liver disease. CONCLUSIONS: Our study found that the abundance of certain strains was associated with the progression of nonalcoholic fatty liver disease.

Deciphering the molecular mechanism underlying the effects of epimedium on osteoporosis through system bioinformatic approach.

Epimedium has gained widespread clinical application in Traditional Chinese Medicine, with the functions of promoting bone reproduction, regulating cell cycle and inhibiting osteoclastic activity. However, its precise cellular pharmacological therapeutic mechanism on osteoporosis (OP) remains elusive. This study aims to elucidate the molecular mechanism of epimedium in the treatment of OP based on system bioinformatic approach. Predicted targets of epimedium were collected from TCMSP, BATMAN-TCM and ETCM databases. Differentially expressed mRNAs of OP patients were obtained from Gene Expression Omnibus database by performing Limma package of R software. Epimedium-OP common targets were obtained by Venn diagram package for further analysis. The protein-protein interaction network was constructed using Cytoscape software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were carried out by using clusterProfiler package. Molecular docking analysis was conducted by AutoDock 4.2 software to validate the binding affinity between epimedium and top 3 proteins based on the result of protein-protein interaction. A total of 241 unique identified epimedium targets were screened from databases, of which 62 overlapped with the targets of OP and were considered potential therapeutic targets. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that these targets were positive regulation of cell cycle, cellular response to oxidative stress and positive regulation of cell cycle process as well as cellular senescence, FoxO, PI3K-Akt, and NF-kappa B signaling pathways. Molecular docking showed that epimedium have a good binding activity with key targets. Our study demonstrated the multitarget and multi-pathway characteristics of epimedium on OP, which elucidates the potential mechanisms of epimedium against OP and provides theoretical basis for further drug development.

TGF-Beta Induced Key Genes of Osteogenic and Adipogenic Differentiation in Human Mesenchymal Stem Cells and MiRNA-mRNA Regulatory Networks.

Background: The clinical efficacy of osteoporosis therapy is unsatisfactory. However, there is currently no gold standard for the treatment of osteoporosis. Recent studies have indicated that a switch from osteogenic to adipogenic differentiation in human bone marrow mesenchymal stem cells (hMSCs) induces osteoporosis. This study aimed to provide a more comprehensive understanding of the biological mechanisms involved in this process and to identify key genes involved in osteogenic and adipogenic differentiation in hMSCs to provide new insights for the prevention and treatment of osteoporosis. Methods: Microarray and bioinformatics approaches were used to identify the differentially expressed genes (DEGs) involved in osteogenic and adipogenic differentiation, and the biological functions and pathways of these genes were analyzed. Hub genes were identified, and the miRNA-mRNA interaction networks of these hub genes were constructed. Results: In an optimized microenvironment, transforming growth factor-beta (TGF-beta) could promote osteogenic differentiation and inhibit adipogenic differentiation of hMSCs. According to our study, 98 upregulated genes involved in osteogenic differentiation and 66 downregulated genes involved in adipogenic differentiation were identified, and associated biological functions and pathways were analyzed. Based on the protein-protein interaction (PPI) networks, the hub genes of the upregulated genes (CTGF, IGF1, BMP2, MMP13, TGFB3, MMP3, and SERPINE1) and the hub genes of the downregulated genes (PPARG, TIMP3, ANXA1, ADAMTS5, AGTR1, CXCL12, and CEBPA) were identified, and statistical analysis revealed significant differences. In addition, 36 miRNAs derived from the upregulated hub genes were screened, as were 17 miRNAs derived from the downregulated hub genes. Hub miRNAs (hsa-miR-27a/b-3p, hsa-miR-128-3p, hsa-miR-1-3p, hsa-miR-98-5p, and hsa-miR-130b-3p) coregulated both osteogenic and adipogenic differentiation factors. Conclusion: The upregulated hub genes identified are potential targets for osteogenic differentiation in hMSCs, whereas the downregulated hub genes are potential targets for adipogenic differentiation. These hub genes and miRNAs play important roles in adipogenesis and osteogenesis of hMSCs. They may be related to the prevention and treatment not only of osteoporosis but also of obesity.

Effect of the amount of correction on posterior tibial slope and patellar height in open-wedge high tibial osteotomy.

Objectives: To evaluate the effect of amount of correction on postoperative changes in PTS (posterior tibial slope), PH (patellar height), and clinical outcomes following biplanar OWHTO (open-wedge high tibial osteotomy). Method: This study included 79 knees (32 left and 47 right) of 79 patients (mean age 60.28 ± 4.2 years, 24 males, 55 females) with varus malalignment and symptomatic isolated medial joint osteoarthritis who underwent OWHTO. According to the amount of correction angles, all patients were divided into three groups: LCA (large correction angle) group (>14°), MCA (medium correction angle) group (10°-14°), and SCA (small correction angle) group (<10°). All patients were clinically assessed according to the Lysholm score, HSS (hospital for special surgery knee score), and KSS (knee society score) prior to and after surgery. For radiographic analysis, we measured the PTS, PH [ISI (Insall-Salvati index), and BPI (Blackburne-Peel index)]. The pre-post difference of PTS, ISI, and BPI was calculated by subtracting the post-OWHTO value to the pre-OWHTO value in three groups, respectively. The preoperative, postoperative, and difference of PTS, ISI, and BPI values were analyzed according to the correction angle. The mean follow-up period was 28.5 months (SD, 4.9; range 18-52 months). Results: Radiologically, PTS increased and PH decreased after surgery on the whole (p < .05). The relationship between amount of correction and slope increase is significant (p < .001). Furthermore, the pairwise difference between the LCA group and SCA group and MCA group is significant respectively (p < .05). In terms of PH, the LCA group yielded ISI and BPI that were significantly different from baseline for the SCA group and MCA group. In addition, the pairwise difference between the SCA group and LCA group in ISI and BPI is significant (p = .031). Clinically, significant improvements were observed in postoperative clinical scores of the Lysholm score, HSS, and KSS (p < .05). Seventy-four patients (93.67%) reported satisfaction with surgery. However, no correlation was found between changes in PTS and PH with postoperative knee score. No severe adverse complications were observed. Conclusions: The amount of correction angle is a significant factor affecting the PTS and PH in OWHTO. With increased correction angle, the likelihood of increasing the PTS and decreasing the PH increases. Special attention should be paid to keep PTS and PH unchanged in cases where large corrections are required. Otherwise, closing wedge osteotomy or other intraoperative effective measures are supposed to be adopted.