Petroleum ether extract of Schisandra sphenanthera prevents hyperglycemia and insulin resistance in association with modulation of sweet taste receptors and gut microbiota in T2DM rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra sphenanthera (Schisandra sphenanthera Rehd. et Wils.) is the dried mature fruit of Schisandra sphenanthera, a plant in the Magnoliaceae family. It was used in the treatment of diabetes mellitus in the Jade Fluid Decoction and the Xiaoke pills, which were recorded in ancient books. However, its mechanism of action in the treatment of type 2 diabetes mellitus (T2DM) was unclear and needs further study. AIM OF THE STUDY: This research aimed to investigate the chemical composition and lignan content of Schisandra sphenanthera petroleum ether parts (SPEP) and to evaluate the effects of SPEP on sweet taste receptors (STRs) and intestinal flora in rats on a high-fat diet (HFD). Additionally, the relationships between SPEP and hyperglycemia and insulin resistance were examined. MATERIALS AND METHODS: GC-MS was used to determine the chemical composition of SPEP, and HPLC was used to determine the lignin content. A combination of the HFD and the administration of streptozotocin (STZ) was employed to generate a rat model of T2DM. Petroleum ether extracts from Schisandra sphenanthera were used as the focus of the research to evaluate the effects of these extracts on the glucolipid metabolism of T2DM rats, as well as the underlying mechanisms. RESULTS: Analysis of the GC-MS spectrum of SESP revealed a total of 58 compounds. HPLC analysis revealed that SPEP had the highest concentration of Schisandrin A and the lowest concentration of Schisandrol A. The drug administration intervention resulted in a significant decrease in body weight and pancreatic weight of diabetic rats compared to the Normal group. When compared to the Model group, the body weight of rats in the drug administration group and the Metformin group had a more moderate decrease, while the pancreatic weight and pancreatic-to-body ratio increased. The Model group shown significant increases in FBG, OGTT, GHb, TC, TG, LDL-C, ALT, AST, MDA, FINS, and NEFA, as well as significant decreases in HDL-C and SOD, when compared to the Normal group (P < 0.05). The administration of each group was found to be significantly effective in decreasing FBG, OGTT, GHb, TC, TG, LDL-C, ALT, AST, MDA, FINS, NEFA, while increasing HDL-C and SOD when compared to the Model group. The application of SPEP had a positive impact on hepatocyte swelling, hepatocyte degeneration, and necrosis, as well as the morphological structure of pancreatic islet cells. Furthermore, the protein expression levels of T1R2, TRPM5 and GLP-1 in the small intestine of the Model group were reduced. After a period of six weeks, the protein expression levels began to align more closely with those of the Normal group of rats. Analysis of 16S rRNA sequencing revealed that the intestinal microbiota of diabetic rats was significantly disrupted, with a decrease in the abundance of the Firmicutes phylum and an increase in the abundance of the Bacteroidetes phylum. Furthermore, the composition of the dominant genus was distinct from that of the control group. After the drug intervention, the microbiota of diabetic rats was significantly altered, exhibiting a higher abundance and diversity, as well as a significant enrichment of the community. The SPEP treatment resulted in a significant increase in acetic acid, propionic acid, and butyric acid. CONCLUSIONS: The findings of this research indicated that SPEP could be effective in treating T2DM through the regulation of STRs, the adjustment of disturbed metabolite levels, and the alteration of intestinal flora.

Knockdown of long non-coding RNA HOTAIR promotes bone marrow mesenchymal stem cell differentiation by sponging microRNA miR-378g that inhibits nicotinamide N-methyltransferase.

Osteoporosis (OP) is associated with a serious social and economic burden. Recent studies have shown that the differential expression of long non-coding RNAs (lncRNAs) is closely related to OP. However, the specific molecular mechanism of HOX transcript antisense intergenic RNA (HOTAIR) remains to be elucidated.The expression of HOTAIR and miR-378g in OP patients was detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured, and osteogenic differentiation was induced. Alkaline phosphatase (ALP) and Runt-related transcription factor 2 (RUNX2) were detected by qRT-PCR, ELISA, and Western blotting. Calcium deposition was measured using Alizarin red s (ARS) staining. Molecular interactions between HOTAIR, miR-378g, and nicotinamide N-methyltransferase (NNMT) were detected using a dual-luciferase reporter assay.HOTAIR expression was upregulated and miR-378g level was downregulated in OP patients. HOTAIR expression decreased during the osteogenic differentiation of BMSCs. Silencing HOTAIR or NNMT reduced ALP and RUNX2 levels and promoted calcium deposition. The overexpression of HOTAIR or interference with miR-378g inhibited the osteogenic differentiation of BMSCs. HOTAIR negatively regulates miR-378g by targeting NNMT.HOTAIR is an miR-378g sponge that targets NNMT, inhibits the osteogenic differentiation of BMSCs, and provides a valuable target for the treatment of OP.

A systematic review and meta-analysis compare surgical treatment and conservative treatment in patients with cervical spondylotic myelopathy.

BACKGROUND: Cervical spondylotic myelopathy (CSM) can be managed by conservative treatment or surgical treatment. This study aimed to compare the clinical effects of conservative treatment versus surgical treatment for patients with CSM. METHODS: Reports of randomized controlled trials and retrospective cohort studies that compared surgical treatment versus conservative treatment for CSM were collated from medical databases. The following data were extracted from eligible studies: pre- and post-treatment Japanese Orthopedic Association (JOA) scores, recovery rate, American Spinal Injury Association (ASIA) scores, and ASIA grade change. Results were expressed as risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CIs). RESULTS: A total of 10 studies were included in this meta-analysis, with a total of 517 patients. Patients who received surgical treatment had lower pre-treatment JOA scores compared to patients who received conservative treatment (P=0.01). However, there was no difference in the post-treatment JOA scores between the two types of treatment (P=0.70). This demonstrated that the increase in JOA score was greater in the surgical group compared to the conservative group. Additionally, patients in the surgical group had a higher recovery rate than patients in the conservative group (P<0.00001). Although this investigation showed no significant difference in ASIA score between the two groups (P=0.30), there was a definite difference in ASIA grade change after sensitivity analysis. DISCUSSION: This meta-analysis suggested that surgical treatment may be more advantageous than conservative treatment in patients with CSM. However, these findings should be verified with larger, multi-centered, follow-up, controlled trials.

Polystyrene microplastics alter the intestinal microbiota function and the hepatic metabolism status in marine medaka (Oryzias melastigma).

To assess the potential effects of microplastics (MPs) on gut microbiome, a simple investigation of gut microbial structure is not sufficient, and the function and association of gut microbial structure with host health should also be taken into account. Here, the effects of two particle sizes (2 and 200 µm) of polystyrene MPs (PS-MPs) on the gut microbiota of medaka were evaluated following oral administration at 0.3 and 3.0 µg/mg for 28 days. No change in body length and gut histopathology damage were observed. However, the exposure to PS-MPs significantly decreased fish body weight and disrupted the liver anti-oxidative status. The PS-MPs caused a shift in the gut microbial structure of medaka accompanied by changes in community function, including significant environmental stress, increased carbon degradation/fixation activities, and partially modified nitrogen/phosphorus/sulfur metabolic abilities. Furthermore, the PS-MPs exposure disturbed the glycolipid/tyrosine/energy metabolism and the endocrine balance. A potential correlation between the gut microecology and host response to PS-MPs exposure was also observed. These results indicated that the PS-MPs may contribute to gut-liver axis disruption, which could be the underlying toxicological mechanisms of PS-MPs exposure. This work has improved our knowledge about the relationship between gut microbiota dysbiosis and host metabolic disorders following MPs exposure.

A facile method for isolation of recombinant human apolipoprotein A-I from E. coli.

Apolipoprotein (apo) A-I is the major protein component of high-density lipoprotein (HDL) and plays key roles in the Reverse Cholesterol Transport pathway. In the past decade, reconstituted HDL (rHDL) has been employed as a therapeutic agent for treatment of atherosclerosis. The ability of rHDL to promote cholesterol efflux from peripheral cells has been documented to reduce the size of atherosclerotic plaque lesions. However, development of apoA-I rHDL-based therapeutics for human use requires a cost effective process to generate an apoA-I product that meets "Good Manufacturing Practice" standards. Methods available for production and isolation of unmodified recombinant human apoA-I at scale are cumbersome, laborious and complex. To overcome this obstacle, a streamlined two-step procedure has been devised for isolation of recombinant untagged human apoA-I from E. coli that takes advantage of its ability to re-fold to a native conformation following denaturation. Heat treatment of a sonicated E. coli supernatant fraction induced precipitation of a large proportion of host cell proteins (HCP), yielding apoA-I as the major soluble protein. Reversed-phase HPLC of this material permitted recovery of apoA-I largely free of HCP and endotoxin. Purified apoA-I possessed α-helix secondary structure, formed rHDL upon incubation with phospholipid and efficiently promoted cholesterol efflux from cholesterol loaded J774 macrophages.