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Background: Diabetic ulcers (DUs) typically occur in patients with vascular diseases and diabetes. Extracellular vesicles secreted by bone marrow-derived stem cells (BMSC-EVs) represent a cell-free therapy that has emerged as a promising alternative for treating DU, especially due to significant advancements in the understanding of their role in promoting angiogenesis; however, their application in DU treatment remains in the preclinical stage, and their effectiveness is still uncertain. Therefore, we conducted this meta-analysis to evaluate the therapeutic efficacy of BMSC-EVs in treating DU and to expedite the clinical translation of BMSC-EV therapy for DU. Methods: We conducted a comprehensive search of PubMed, Cochrane Library, MEDLINE, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, and our self-constructed database of Chinese Biomedical Literature up to May 2023 to identify preclinical studies related to the therapeutic use of extracellular vesicles secreted by bone marrow-derived stem cells for treating diabetic ulcers. Outcome measures included wound healing rate, neovascularization density, a-sma, and CD31. RevMan 5 software was employed for all statistical analyses. Results: In this meta-analysis, a total of 11 studies involving 103 animals were identified. The pooled analysis indicated that BMSC-EV treatment showed a superior wound healing rate compared to that of the control group (SMD = 1.06, 95% CI [0.52, 1.60], P = 0.0001). In the subgroup analysis, EV combined with new materials or drug therapy performed better than the sole injection of extracellular vesicles (SMD = 1.85, 95% CI [0.87, 2.82], P < 0.00001). BMSC-EV treatment also resulted in a higher number of neovascular structures compared to the control group(SMD = 5.80, 95% CI[0.89,10.71], P = 0.006). In the subgroup analysis, EV combined therapy showed a significant difference in the number of blood vessels compared to the sole injection of extracellular vesicles (SMD = 4.90, 95% CI[2.64,7.15], P < 0.00001). However, BMSCs-EV treatment did not demonstrate any statistically significant difference in the angiogenesis-related indicators CD31 and α-SMA compared to the control group (SMD = 1.61, 95% CI[-0.51,3.74], P = 0.14). Conclusion: According to the current meta-analysis, BMSC-EV therapy can enhance the healing of diabetic ulcers and promote wound angiogenesis, particularly when used in combination with novel dressings or other drugs, which further accelerates the healing process of diabetic ulcers. To establish the most effective parameters for EV treatment in diabetic ulcers, future research should promptly progress into clinical trials.
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In recent years, pumps have become critical components in agriculture, industry, and the military, necessitating extensive development and implementation of the fault diagnosis method. In the majority of existing fault classification models, the connection between performance improvement and the amount of training data remains high, yet real-world samples are difficult to obtain. Combining domain migration theory and sample expansion method, this paper introduces a few-shot learning fault diagnosis method. Employing the T-SNE visualization algorithm, we examine the validity of the self-calibration attention mechanism (SCAM) and distribution edge prediction strategy (DEPS). The accomplishment demonstrated that the proposed algorithm could effectively map the expanded sample space within a separate interval, thereby avoiding the problem of feature aliasing caused by the overlap of sample features among similar categories and significantly enhancing the quality and quantity of training samples. The experimental analysis indicates that the proposed methodology can effectively increase the accuracy of few-shot tasks, especially in the 9way-15shot task, where it maintains a performance of 72 %, which leading the mean accuracy calculated from the others of about 30%. It is believed that much of the work has superior applicability to other few-shot diagnosis cases.
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Venlafaxine (VEN), a first-line antidepressant, and Zuojin Pill (ZJP), a common herbal medicine consisting of Rhizoma Coptidis and Fructus Evodiae, are high likely co-administered in China. ZJP could significantly inhibit VEN pharmacokinetics in vitro and in rats through suppression of CYP2D6 activity. To date, however, no clinical study has demonstrated the clinical relevance. Here, the VEN pharmacokinetics at a single dose of VEN with or without co-administration of ZJP was compared. ZJP had a weak herb-drug interactions (HDI) on the pharmacokinetics of VEN. The geometric means of Cmax and AUC0-∞ of VEN increased by 36.7% and 34.6%, respectively, and the corresponding 90% confidence intervals (CIs) of geometric mean ratios (GMRs) exceed outside bioequivalent range of 0.80-1.25. However, the corresponding 90% CIs of GMRs of these parameters for ODV were within the range. Since ODV exposure (AUC), approximately 3.4-fold higher than that of VEN, hardly changed, the systemic exposure of VEN active moiety (VEN + ODV) with ZJP increased slightly (≤8.5%) compared with that of VEN alone. In addition, the incidence of VEN-related side effects, especially gastrointestinal relevance, was significantly reduced with ZJP. Therefore, rational concomitant use of VEN and ZJP might have low risk of HDI and be promising in clinical practice.
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Medicamentos Herbarios Chinos , Animales , Antidepresivos , Medicamentos Herbarios Chinos/farmacología , Interacciones de Hierba-Droga , Humanos , Ratas , Clorhidrato de Venlafaxina/efectos adversos , Clorhidrato de Venlafaxina/farmacocinéticaRESUMEN
The inhibition of α-glucosidase by nine galloyl-based polyphenols with free and unfree galloyl moieties (GMs) was studied. The results show that the inhibitory activity increased with the free GM number increasing. For the compounds with unfree GMs, ellagic acid and hexahydroxydiphenoyl group contributed to the enzyme inhibition. Free GMs could bind not only with the active site of α-glucosidase (competitive inhibition character), but also with the non-active sites (uncompetitive one); however, the former binding interaction was stronger than the latter one. All polyphenols that had inhibitory effects quenched α-glucosidase fluorescence in a static mode through forming a polyphenol-enzyme complex. The number of amino acid residues involved in polyphenol-enzyme binding interactions (hydrogen bonding and π-conjugations) increased with the inhibitory activity increasing. Additionally, two polyphenols with 5 free GMs showing certain hypoglycemic effects in maltose-loading test suggests that GM may be an advisable functional factor for alleviation of type II diabetes symptoms.
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Diabetes Mellitus Tipo 2 , alfa-Glucosidasas , Inhibidores de Glicósido Hidrolasas , Humanos , Simulación del Acoplamiento Molecular , PolifenolesRESUMEN
d- chiro-Inositol (DCI) is a biologically active component found in tartary buckwheat, which can reduce hyperglycemia and ameliorate insulin resistance. However, the mechanism underlying the antidiabetic effects of DCI remains largely unclear. This study investigated the effects and underlying molecular mechanisms of DCI on hepatic gluconeogenesis in mice fed a high fat diet and saturated palmitic acid-treated hepatocytes. DCI attenuated free fatty acid uptake by the liver via lipid trafficking inhibition, reduced diacylglycerol deposition, and hepatic PKCε translocation. Thus, DCI could improve insulin sensitivity by suppressing hepatic gluconeogenesis. Subsequent analyses revealed that DCI decreased hepatic glucose output and the expression levels of PEPCK and G6 Pase in insulin resistant mice through PKCε-IRS/PI3K/AKT signaling pathway. Likewise, such effects of DCI were confirmed in HepG2 cells with palmitate-induced insulin resistance. These findings indicate a novel pathway by which DCI prevents hepatic gluconeogenesis, reduces lipid deposition, and ameliorates insulin resistance via regulation of PKCε-PI3K/AKT axis.