The role of autophagy in the treatment of type II diabetes and its complications: a review.

Type II diabetes mellitus (T2DM) is a chronic metabolic disease characterized by prolonged hyperglycemia and insulin resistance (IR). Its incidence is increasing annually, posing a significant threat to human life and health. Consequently, there is an urgent requirement to discover effective drugs and investigate the pathogenesis of T2DM. Autophagy plays a crucial role in maintaining normal islet structure. However, in a state of high glucose, autophagy is inhibited, resulting in impaired islet function, insulin resistance, and complications. Studies have shown that modulating autophagy through activation or inhibition can have a positive impact on the treatment of T2DM and its complications. However, it is important to note that the specific regulatory mechanisms vary depending on the target organ. This review explores the role of autophagy in the pathogenesis of T2DM, taking into account both genetic and external factors. It also provides a summary of reported chemical drugs and traditional Chinese medicine that target the autophagic pathway for the treatment of T2DM and its complications.

The clinical effect of modified slow Mohs circular skin biopsy on penoscrotal extramammary Paget's disease.

OBJECTIVE: Determining the tumor margin is the main problem in penoscrotal extramammary Paget's disease (PEMPD) surgery. This study aimed to explore the role of modified slow Mohs circular skin biopsy in determining the tumor margin in patients with PEMPD before operation. METHODS: Thirty-six PEMPD patients were divided into the control group and the observation group according to the simple randomization method. The control group, which consisted of 16 patients, underwent wide local excision, and the observation group, which consisted of 20 patients, underwent a modified slow Mohs circular skin biopsy to determine the tumor margin before surgery. The duration of surgery, number of frozen sections, satisfaction with the appearance of the skin, tumor recurrence rate, and incidence of functional sequelae were statistically analyzed. RESULTS: The number of frozen sections, duration of surgery, incidence of functional sequelae, and tumor recurrence rate in the observation group were lower than in the control group. The satisfaction with the appearance of the skin was higher in the observation group than in the control group, and the difference was statistically significant (P < 0.05). CONCLUSION: Modified slow Mohs circular skin biopsy can determine the tumor margin before surgery and reduce the number of frozen sections, tumor recurrence rate, and the incidence of functional sequelae. It also increases the postoperative satisfaction of patients.

Study on the Antipyretic and Anti-inflammatory Mechanism of Shuanghuanglian Oral Liquid Based on Gut Microbiota-Host Metabolism.

Nowadays, there has been increased awareness that the therapeutic effects of natural medicines on inflammatory diseases may be achieved by regulating the gut microbiota. Shuanghuanglian oral liquid (SHL), the traditional Chinese medicine preparation, has been shown to be effective in clearing heat-toxin, which is widely used in the clinical treatment of respiratory tract infection, mild pneumonia, and common cold with the wind-heat syndrome. Yet the role of gut microbiota in the antipyretic and anti-inflammatory effects is unclear. In this study, a new strategy of the 16S rRNA gene sequencing and serum metabolomics that aims to explore the role of SHL in a rat model of the systemic inflammatory response induced by lipopolysaccharide would be a major advancement. Our results showed that the gut microbiota structure was restored in rats with inflammation after oral administration of SHL, thereby reducing inflammation. Specifically, SHL increased the relative abundance of Bacteroides and Faecalibacterium and decreased the abundance of Bifidobacterium, Olsenella, Aerococcus, Enterococcus, and Clostridium in the rat model of inflammatory disease. Serum metabolomic profile obtained by the orbitrap-based high-resolution mass spectrometry revealed significant differences in the levels of 39 endogenous metabolites in the inflammatory model groups, eight metabolites of which almost returned to normal levels after SHL treatment. Correlation analysis between metabolite, gut microbiota, and inflammatory factors showed that the antipyretic and anti-inflammatory effects of SHL were related to the recovery of the abnormal levels of the endogenous metabolites (N-acetylserotonin and 1-methylxanthine) in the tryptophan metabolism and caffeine metabolism pathway. Taken together, these findings suggest that the structural changes in the gut microbiota are closely related to host metabolism. The regulation of gut microbiota structure and function is of great significance for exploring the potential mechanism in the treatment of lipopolysaccharide-induced inflammatory diseases with SHL.

Undescribed ecdysteroids and phenolic glycosides from the roots of Cyathula officinalis Kuan and their anti-inflammatory activity in LPS-induced RAW 264.7 macrophages in vitro.

Six undescribed compounds, including four undescribed ecdysteroids (cyathsterones A-D) and two undescribed phenolic glycosides (cyathglucosides A-B), were isolated from the roots of Cyathula officinalis Kuan. Their structures were based on chemical analyses, NMR spectroscopic evidence, DP4+ calculations, and hydrolysis products. All compounds inhibited NO release in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in vitro. Among them, cyathsterone A showed the strongest inhibitory effects. Moreover, cyathsterone A has been shown to inhibit the release of the proinflammatory cytokines TNF-α, IL-6, and IL-1ß in LPS-induced RAW 264.7 macrophages in vitro. Further studies found that cyathsterone A present concentration-dependent suppression of the protein expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells in vitro and exerted anti-inflammatory activity via the NF-κB signalling pathway.

Interventions to promote the implementation of pressure injuries prevention measures in nursing homes: a scoping review protocol.

INTRODUCTION: Currently, various guidelines and documents on the prevention of pressure injuries have been published, but there are many serious lags in the actual practice in nursing homes. So some interventions are required to promote the implementation of normative practices. There was a review of preventive interventions for pressure injuries in long-term care facilities, but there is no systematic review of how to promote the implementation of preventive measures. This review aims to summarise interventions that promote the implementation of pressure injuries prevention measures in nursing homes, explore the research scope and gaps in this field and provide evidence and striving direction for global nursing homes to improve existing preventive behaviours. METHODS AND ANALYSIS: This scoping review will combine the Arksey and O'Malley framework with further clarification and advice of the scoping review by Levac et al as methodological guidance. Systematic retrieval of relevant literature databases, grey literature and references included studies will be conducted. Two reviewers will screen titles and abstracts independently, and then screen the full text of potentially relevant articles to determine final inclusion. After that, two reviewers will extract data based on a predesigned data extraction table independently. Inductive analysis and narrative analysis will be used to collate, summarise and report the results. Finally, managers of nursing homes in China will be consulted for additional information and their viewpoints on the research findings. ETHICS AND DISSEMINATION: Since the scoping review is a secondary analysis of the literature, there is no need to apply for ethical approval. Our goal is to share the results with key stakeholders to help them find the direction of effort and improve clinical practice. Therefore, dissemination plans include publication in international journals and sharing it at conferences to inform more healthcare workers about the scope and gaps of the studies.

CD73 Severed as a Potential Prognostic Marker and Promote Lung Cancer Cells Migration via Enhancing EMT Progression.

To investigate the expression levels and prognostic value of CD73 in lung cancer. And moreover, to identify the effect and potential mechanism of CD73 on lung cancer cells proliferation and migration. CD73 expression levels in lung cancer were analyzed base on GEPIA2 and GEO database. GEPIA2 and Kaplan-Meier Plotter (KM Plotter) was used to analyzed the correlation between CD73 expression and prognosis. GEO dataset were analyzed via GEO2R. CD73 overexpression cell model was construction via recombinant lentivirus transfection into A549 and NCI-H520 cells. CCK8 assay were used to investigate cells proliferation. Migration and invasion ability were evaluated by scratch and transwell methods. Base on GEPIA2, GSE32683, GSE116959 and GSE37745 dataset, we found that CD73 expression were significant higher in tumor tissues of lung adenocarcinoma (LUAD) compared with that in non-tumor normal tissues and in lung squamous cell carcinoma (LUSC), while there were no significant difference of CD73 expression between LUSC and normal control tissues. Interestingly, a high CD73 level predict poor overall survival (OS) of LUSC. However, GEPIA2 and KM plotter showed the opposite conclusion of prognostic value of CD73 in LUAD. By using cell experiments, we found that CD73 overexpression promoted proliferation and migration of LUAD A549 cells. However, there was no significant effect of CD73 overexpression on LUSC NCI-H520 cells. Furthermore, CD73 overexpression facilitates epithelial to mesenchymal transition (EMT) progression of A549 cells. In conclusion, our results indicated that CD73 expression were increased in LUAD and might be an poor prognostic marker for LUSC patients. CD73 play an important role in LUAD cells proliferation and migration. These data allowed to support CD73 as a therapeutic target for LUAD.

[Phenylpropanoids from Zanthoxylum species and their pharmacological activities: a review].

Phenylpropanoids are one of the major chemical constituents in Zanthoxylum species. They include simple phenylpropanoids, coumarins, and lignans and possess anti-tumor, anti-inflammatory, anti-platelet aggregation, anti-bacterial, anti-viral, insecticidal, and antifeedant activities. This review summarizes the chemical constituents and pharmacological activities from the Zanthoxylum plants in hopes of providing reference for the research and application of phenylpropanoids from this genus.

Post-treatment with glycyrrhizin can attenuate hepatic mitochondrial damage induced by acetaminophen in mice.

Overdose of acetaminophen (APAP) is responsible for the most cases of acute liver failure worldwide. Hepatic mitochondrial damage mediated by neuronal nitric oxide synthase- (nNOS) induced liver protein tyrosine nitration plays a critical role in the pathophysiology of APAP hepatotoxicity. It has been reported that pre-treatment or co-treatment with glycyrrhizin can protect against hepatotoxicity through prevention of hepatocellular apoptosis. However, the majority of APAP-induced acute liver failure cases are people intentionally taking the drug to commit suicide. Any preventive treatment is of little value in practice. In addition, the hepatocellular damage induced by APAP is considered to be oncotic necrosis rather than apoptosis. In the present study, our aim is to investigate if glycyrrhizin can be used therapeutically and the underlying mechanisms of APAP hepatotoxicity protection. Hepatic damage was induced by 300 mg/kg APAP in balb/c mice, followed with administration of 40, 80, or 160 mg/kg glycyrrhizin 90 min later. Mice were euthanized and harvested at 6 h post-APAP. Compared with model controls, glycyrrhizin post-treatment attenuated hepatic mitochondrial and hepatocellular damages, as indicated by decreased serum glutamate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities as well as ameliorated mitochondrial swollen, distortion, and hepatocellular necrosis. Notably, 80 mg/kg glycyrrhizin inhibited hepatic nNOS activity and its mRNA and protein expression levels by 16.9, 14.9, and 28.3%, respectively. These results were consistent with the decreased liver nitric oxide content and liver protein tyrosine nitration indicated by 3-nitrotyrosine staining. Moreover, glycyrrhizin did not affect the APAP metabolic activation, and the survival rate of ALF mice was increased by glycyrrhizin. The present study indicates that post-treatment with glycyrrhizin can dose-dependently attenuate hepatic mitochondrial damage and inhibit the up-regulation of hepatic nNOS induced by APAP. Glycyrrhizin shows promise as drug for the treatment of APAP hepatotoxicity.

Prevalence and risk factors for postoperative delirium in patients with colorectal carcinoma: a systematic review and meta-analysis.

OBJECTIVE: Postoperative delirium (POD) is a common, but severe complication in elderly patients undergoing surgery for colorectal cancer, but the prevalence and potential risk factors for POD were not well established. Therefore, a meta-analysis was preformed to clarify the prevalence and risk factors of POD in patients undergoing surgery for colorectal cancer. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched on August 2019. Studies were included if they reported the prevalence and risk factors of POD in patients undergoing colorectal cancer surgery. The guidelines for critically appraising studies of prevalence or incidence of a health problem were used to assess the quality of included studies. Pooled odds ratios (ORs) for individual risk factors were estimated using the Mantel-Haenszel methods in random effect model. Sensitive analyses based on different inclusion criteria were conducted to explore whether the current meta-analysis was enough credible and robust. RESULTS: Seventeen studies totaling 4472 patients undergoing colorectal cancer surgery were included. The pooled prevalence of POD is 14% (95% CI = 12-17%). Twelve significant risk factors were identified in pooled analysis including older age (OR = 1.10), sex (OR = 1.87), history of psychiatric disease (OR = 6.47), comorbidities (OR = 2.17), prognostic nutritional index (OR = 1.12), physical status (OR = 1.27), American Society of Anesthesiologists Score (ASA Scores) (OR = 1.65), history of alcohol abuse (OR = 2.23), postoperative pain management (OR = 1.91), perioperative blood transfusion (OR = 2.37), cognitive status (OR = 1.91), and lower serum level of albumin (OR = 0.58). CONCLUSIONS: POD is a frequent complication in patients undergoing surgery with colorectal cancer. Several risk factors including history of psychiatric disease, transfusion, comorbidities, male gender, and old age were significant predictors for POD.

[Advances on chemical constituents of Tibetan Salvia genus].

Salvia is the largest genus of Labiatae family, and there are more than 1 000 species around the world. Our country is rich in the resources of Salvia plants. The plants of this genus contain multiple chemical components, including sesquiterpenoids, diterpenoids, triterpenoids and phenols, et al. In order to develop better Tibetan plants of Salvia genus, this article reviewed and summarized the constituents from Tibetan Salvia genus.

Induction of mitochondria-mediated apoptosis in human gastric adenocarcinoma SGC-7901 cells by kuraridin and Nor-kurarinone isolated from Sophora flavescens.

The study was designed as one of a series to find novel anticancer compounds from Chinese herbs. For this purpose, we screened an ethanol extract of 300 herbs against SGC-7901 cells. Sophora flavescen was included in those showing potential cytotoxic activity. Target compounds were therefore isolated and analyzed on analytical HPLC. Chromatography showed only one peak with a purity of 97%. The ESI-MS spectrum showed two molecular ions: m/z 424(M+) and 438(M+). Furthermore, combining the data of 1HNMR and 13CNMR, it was deduced that this product was a mixture of two compounds; kuraridin (1) and nor-kurarinone (2). The concentration was [1]:[2]=9:10, the chemical structural formulae are C25H28O6 and C26H30O6. In this study, mechanisms involved by the mixture of compounds 1 and 2-induced growth inhibition including apoptosis and G2/M phase arrest in human gastric adenocarcinoma SGC-7901 cells were examined for the first time. Triggering of the mitochondrial apoptotic pathway was demonstrated by loss of mitochondrial membrane potential, reduction in the Bcl-2/Bax ratio, and significant activation and cleavage of caspase-3. Additionally, the production of reactive oxygen species (ROS) was also increased. Taken together, our results indicated that the cytotoxic efficacy of the mixture of compounds 1 and 2 is mainly due to induction of cell cycle arrest and apoptosis.