Shenling Baizhu powder alleviates non-alcoholic fatty liver disease by modulating autophagy and energy metabolism in high-fat diet-induced rats.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has emerged as a burgeoning health problem worldwide, but no specific drug has been approved for its treatment. Shenling Baizhu powder (SL) is extensively used to treat NAFLD in Chinese clinical practice. However, the therapeutic components and pharmacological mechanisms of SL against NAFLD have not been thoroughly investigated. PURPOSE: This study aimed to investigate the pharmacological impact and molecular mechanism of SL on NAFLD. METHODS: First, we established an animal model of NAFLD by high-fat diet (HFD) feeding, and evaluated the therapeutic efficacy of SL on NAFLD by physiological, biochemical, pathological, and body composition analysis. Next, the effect of SL on autophagic flow in NAFLD rats was evaluated by ultrastructure, immunofluorescence staining, and western blotting. Moreover, an integrated strategy of targeted energy metabolomics and network pharmacology was performed to characterize autophagy-related genes and explore the synergistic effects of SL active compounds. UPLC-MS/MS, molecular docking combined with in vivo and in vitro experiments were conducted to verify the key compounds and genes. Finally, a network was established among SL-herb-compound-genes-energy metabolites-NAFLD, which explains the complicated regulating mechanism of SL on NAFLD. RESULTS: We discovered that SL decreased hepatic lipid accumulation, hepatic steatosis, and insulin resistance, and improved systemic metabolic disorders and pathological abnormalities. Subsequently, an integrated strategy of targeted energy metabolomics and network pharmacology identified quercetin, ellagic acid, kaempferol, formononetin, stigmasterol, isorhamnetin and luteolin as key compounds; catalase (CAT), AKT serine/threonine kinase 1 (AKT), nitric oxide synthase 3 (eNOS), NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase 1 (HO-1) and hypoxia-inducible factor 1 subunit alpha (HIF-1α) were identified as key genes; while nicotinamide adenine dinucleotide phosphate (NADP) and succinate emerged as key energy metabolites. Mechanistically, we revealed that SL may exert its anti-NAFLD effect by inducing autophagy activation and forming a comprehensive regulatory network involving key compounds, key genes, and key energy metabolites, ultimately alleviating oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction. CONCLUSION: Our study demonstrated the therapeutic effect of SL in NAFLD models, and establishes a basis for the development of potential products from SL plant materials for the treatment of NAFLD.

CD73-positive pediatric urethral mesenchymal stem-like cell-derived small extracellular vesicles stimulate angiogenesis.

Introduction: Angiogenesis plays an important role in the repair of urethral injury, and stem cells and their secretomes can promote angiogenesis. We obtained pediatric urethral mesenchymal stem-like cells (PU-MSLCs) in an earlier study. This project studied the pro-angiogenic effect of PU-MSLC-derived small extracellular vesicles (PUMSLC-sEVs) and the underlying mechanisms. Materials and methods: PUMSLCs and PUMSLC-sEVs were cultivated and identified. Then, biological methods such as the ethynyl deoxyuridine (EdU) incorporation assay, Cell Counting Kit-8 (CCK-8) assay, scratch wound assay, Transwell assay, and tube formation assay were used to study the effect of PUMSLC-sEVs on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). We explored whether the proangiogenic effect of PUMSLC-sEVs is related to CD73 and whether adenosine (ADO, a CD73 metabolite) promoted angiogenesis. GraphPad Prism 8 software was used for data analysis. Results: We observed that PUMSLC-sEVs significantly promoted the proliferation, migration, and tube-forming abilities of HUVECs. PUMSLC-sEVs delivered CD73 molecules to HUVECs to promote angiogenesis. The angiogenic ability of HUVECs was enhanced after treatment with extracellular ADO produced by CD73, and PUMSLC-sEVs further promoted angiogenesis by activating Adenosine Receptor A2A (A2AR). Conclusions: These observations suggest that PUMSLC-sEVs promote angiogenesis, possibly through activation of the CD73/ADO/A2AR signaling axis.

Investigation of Penetration Performance of Zr-based Amorphous Alloy Liner Compared with Copper.

Zr-based amorphous alloy is a new type of metastable energetic material, which has been exploringly used to design shaped charge (SC) liners by scholars of the military industry. In order to know well how the stand-off distance influences jet penetration performance of liners made by such energetic materials against metal targets, SC static explosion tests were conducted under the same initiation and target conditions but different stand-off distances compared with copper liners. Test results indicate that the jet depth of penetration (DOP) of Zr-based amorphous alloy liners firstly increases slowly and then decreases sharply as the stand-off becomes larger. The optimum stand-off distance is 3.5 times of charge diameter (CD) and the corresponding maximum DOP is about 2.68 CD against the 45# steel plate. The perforation area varies with the stand-off distance. It reaches the maximum when the stand-off is 3.5 CD and the corresponding perforation diameter is about 42mm, also the penetration hole is nearly circular. The jet DOP of Zr-based amorphous alloy liner is smaller than that of copper liner's while the perforation area is the opposite. The former DOP is about 55.7% of the latter and the former perforation area is about 2.8 times of latter when the stand-off distance is 3.5 CD.

Outcome of palliative total gastrectomy for stage IV proximal gastric cancer.

BACKGROUND: A few studies have investigated the outcome of palliative total gastrectomy (PTG) in stage IV proximal gastric cancer. In this study, we tried to summarize the outcome of PTG in stage IV proximal gastric cancer. METHODS: Between January 1991 and January 2005, complete clinical data of 197 patients with stage IV proximal gastric cancer undergoing PTG, 642 patients undergoing curative total gastrectomy (CTG), 152 nonsurgical patients, 102 patients undergoing explorative laparotomy, and 78 patients undergoing jejunostomy were enrolled in this study. Survival rates, median survival, complication rates, and mortality were analyzed. RESULTS: The 1-year, 3-year, and 5-year survival rates were 61.3%, 8.9%, and 6.4% in the PTG group, respectively, and 92.3%, 58.5%, and 48.9% in the CTG group, respectively (P < .05). The median survival periods in the PTG, no surgery, laparotomy, and jejunostomy groups were 16.4, 5.5, 4.7, and 5.8 months, respectively. The median survival in the PTG group was significantly longer than that in the other 3 groups (P < .05). The postoperative complication rate and mortality rate were, respectively, 24.3% and 3.0% in the PTG group and 13.5% and 2.3% in the CTG group (P > .05). CONCLUSIONS: PTG for stage IV proximal gastric cancer when compared with no surgery, laparotomy, and jejunostomy is associated with prolonged survival time and improved quality of life. However, despite the feasibility and safety of PTG, patients with stage IV proximal gastric cancer who are suitable for this treatment should be selected, and thoughtful preparation should be made in the perioperative period.