Epigallocatechin-3-gallate Alleviates Ethanol-Induced Endothelia Cells Injury Partly through Alteration of NF-κB Translocation and Activation of the Nrf2 Signaling Pathway.

Ethanol (alcohol) is a risk factor that contributes to non-communicable diseases. Chronic abuse of ethanol is toxic to both the heart and overall health, and even results in death. Ethanol and its byproduct acetaldehyde can harm the cardiovascular system by impairing mitochondrial function, causing oxidative damage, and reducing contractile proteins. Endothelial cells are essential components of the cardiovascular system, are highly susceptible to ethanol, either through direct or indirect exposure. Thus, protection against endothelial injury is of great importance for persons who chronic abuse of ethanol. In this study, an in vitro model of endothelial injury was created using ethanol. The findings revealed that a concentration of 20.0 mM of ethanol reduced cell viability and Bcl-2 expression, while increasing cell apoptosis, intracellular reactive oxygen species (ROS) levels, mitochondrial depolarization, and the expression of Bax and cleaved-caspase-3 in endothelial cells. Further study showed that ethanol promoted nuclear translocation of nuclear factor kappa B (NF-κB), increased the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 in the culture medium, and inhibited nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway. The aforementioned findings suggest that ethanol has a harmful impact on endothelial cells. Nevertheless, the application of epigallocatechin-3-gallate (EGCG) to the cells can effectively mitigate the detrimental effects of ethanol on endothelial cells. In conclusion, EGCG alleviates ethanol-induced endothelial injury partly through alteration of NF-κB translocation and activation of the Nrf2 signaling pathway. Therefore, EGCG holds great potential in safeguarding individuals who chronically abuse ethanol from endothelial dysfunction.

[Effect of Selenoprotein Thioredoxin Reductase 3 on the Survival Prognosis of Tumor Patients].

Objective To investigate the expression of thioredoxin reductase 3(TXNRD3),a selenoprotein,in 33 human malignant tumors and then analyze its effect on the survival prognosis.Methods We employed the genotype-tissue expression project database,the cancer cell line encyclopedia,and the cancer genome atlas to explore the expression of TXNRD3 gene in 33 human malignant tumors and analyze its impact on the survival prognosis.Further,we explored the correlations of TXNRD3 with immune cells and immune infiltration in the tumor microenvironment,as well as with neoantigens,immune checkpoint genes,tumor mutational burden,and microsatellite instability.Subsequently,human samples were classified into high-and low-expression groups according to TXNRD3 gene expression levels,and the enrichment analysis of biological functions and signaling pathways was performed.Results The analysis with multiple databases showed that TXNRD3 was highly expressed in 15 tumors.The survival analysis showed that TXNRD3 was significantly associated with poor prognosis in pancreatic cancer patients.In addition,the expression level of TXNRD3 was correlated with immune infiltration in tumor microenvironment,neoantigens,immune checkpoint genes,tumor mutational burden,and microsatellite instability.TXNRD3 affected the expression of DNA mismatch repair genes.The gene set enrichment indicated that TXNRD3 was involved in regulating multiple signaling pathways associated with tumor metabolism and tumor immunity.Conclusion TXNRD3 is widely expressed in tumors and has a clinical value for the survival prognosis prediction and treatment of multiple tumors,demonstrating the potential of being a promising biomarker for targeted treatment of multiple tumors.

[Expression of Glutathione Peroxidases and Its Effect on Clinical Prognosis in Glioma Patients].

Objective To investigate the relationship between the expression of glutathione peroxidase(GPX)genes and the clinical prognosis in glioma patients,and to construct and evaluate the model for predicting the prognosis of glioma. Methods The clinical information and GPX expression of 663 patients,including 153 patients of glioblastoma(GBM)and 510 patients of low-grade glioma(LGG),were obtained from The Cancer Genome Atlas(TCGA)database.The relationship between GPX expression and patient survival was analyzed.The key GPX affecting the prognosis of glioma was screened out by single- and multi-factor Cox's proportional-hazards regression models and validated by least absolute shrinkage and selection operator(Lasso)regression.Finally,we constructed the model for predicting the prognosis of glioma with the screening results and then used concordance index and calibration curve respectively to evaluate the discrimination and calibration of model. Results Compared with those in the control group,the expression levels of GPX1,GPX3,GPX4,GPX7,and GPX8 were up-regulated in glioma patients(all P<0.001).Moreover,the expression levels of other GPX except GPX3 were higher in GBM patients than in LGG patients(all P<0.001).The Kaplan-Meier curves showed that the progression-free survival of GBM with high expression of GPX1(P=0.013)and GPX4(P=0.040),as well as the overall survival,disease-specific survival,and progression-free survival of LGG with high expression of GPX1,GPX7,and GPX8,was shortened(all P<0.001).GPX7 and GPX8 were screened out as the key factors affecting the prognosis of LGG.The results were further used to construct a nomogram model,which suggested GPX7 was the most important variable.The concordance index of the model was 0.843(95%CI=0.809-0.853),and the calibration curve showed that the predicted and actual results had good consistency. Conclusion GPX7 is an independent risk factor affecting the prognosis of LGG,and the nomogram model constructed with it can be used to predict the survival rate of LGG.

[Expression and Regulatory Mechanism of Autophagy-related Genes in Synovial Tissues of Patients with Rheumatoid Arthritis].

Objective To investigate the expression regulation of autophagy-related genes(ATG)and the mechanism of autophagy in rheumatoid arthritis(RA).Methods The differentially expressed genes(DEG)of RA were identified from GSE55235 and GSE55457,on the basis of which the differentially expressed autophagy-related genes(DE-ATG)were selected from the Human Autophagy Database.STRING 11.0 and GeneMANIA were used to establish protein-protein interaction networks.Further,the transcription factor-gene-miRNA co-expression network was established via NetworkAnalyst and Cytoscape.Finally,receiver operating characteristic(ROC)curve and DrugBank were employed to evaluate the efficacy of the predicted biomarkers and the performance of drugs targeting DE-ATG.GraphPad Prism 8.2.1 and R 4.0.3 were used for statistical analysis and graphics.Results A total of 485 DEG were enriched in signaling pathways such as T cell activation,hormone regulation,osteoclast differentiation,RA,and chemokines.Eleven DE-ATG regulated the expression of RUNX1,TP53,SOX2,and hsa-mir-155-5p in synovial tissues of RA patients and were involved in the response to environmental factors such as 2,3,7,8-tetrachlorodibenzodioxin and silicon dioxide.The ROC curve analysis identified the DE-ATG with good sensitivity and specificity,such as MYC,MAPK8,CDKN1A,and TNFSF10,which can be used to distinguish certain phenotypes and serve as novel biomarkers for RA.Conclusions In RA,down-regulated DE-ATG expression may promote apoptosis and lysis of chondrocytes.The identified novel biomarkers provides new ideas and methods for diagnosing and treating RA.The establishment of transcription factor-miRNA-gene co-expression network provides direct evidence for dissecting synovial inflammation and articular cartilage destruction.

Glutathione peroxidase family and survival prognosis in patients with renal cell carcinoma. / è°·èƒ±ç”˜è‚½è¿‡æ°§åŒ–ç‰©é ¶å®¶æ—ä¸Žè‚¾ç»†èƒžç™Œæ‚£è€ ç”Ÿå­˜é¢„åŽçš„å ³ç³».

OBJECTIVES: Renal cell carcinoma (RCC) is a renal cortical tumor with high clinical incidence. The effect of glutathione peroxidases (GPXs) on RCC and the possible mechanism are still unclear. This study aims to explore the expression level of GPXs gene in RCC and its effect on the clinical prognosis of patients with RCC via bioinformatics analysis. METHODS: The mRNA expressions of GPXs family genes were obtained from the public data of The Cancer Genome Atlas (TCGA) database. The Kruskal-Wails test was used to analyze the differences in mRNA expression of GPXs family genes between samples from patients with RCC and the normal population. UALAN databases were used to analyze the differences in protein expression of GPXs family genes between samples from patients with renal clear cell carcinoma and the normal population, and to evaluate the role of GPXs family genes in RCC. The Kaplan-Meier Plotter was used to analyze the correlation between different types of RCC and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS). Kaplan-Meier survival curve was drawn based on the GPX8 gene expression to study the relationship between GPX8 gene expression and prognosis of RCC patients. Based on the results of multivariate Cox regression analysis, a Nomogram scoring model for RCC prediction was established by introducing GPX8 gene. RESULTS: The mRNA expressions of GPX1 and GPX4 were higher in the sample of renal chromophobe cell carcinoma, renal clear cell carcinoma, and renal papillary cell carcinoma than those in the normal population (all P<0.01), and GPX7 and GPX8 were significantly over-expressed in patients with renal papillary cell carcinoma and renal clear cell carcinoma (all P<0.01). Compared with the normal group, the protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in renal clear cell carcinoma (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). The protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in patients with renal clear cell carcinoma at different tumor grades (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). Survival analysis showed that OS, DFS, DSS, and PFS were all decreased in patients with clear cell carcinoma compared with patients with papillary cell carcinoma and chromophobe cell carcinoma. According to the GPX8 level, patients were assigned into the low, medium, and high expression groups. Compared with the low GPX8 level group, the OS (P<0.01), DFS (P=0.03), DSS (P<0.01), and PFS (P=3.18×10-7) were significantly decreased in the high level group. Univariate Cox proportional regression analysis showed that the high level of GPX8 was associated with poor OS of 3 different types of renal cancer. Multifactorial analysis showed that GPX8 was an independent factor affecting the OS of patients with renal papillary cell carcinoma. Race and post tumor node metastasis (pTNM) typing were independent factors influencing the OS of patients with renal clear cell carcinoma. GPX8 and pTMN were independent factors influencing the OS of patients with renal chromophobe cell carcinoma. Based on these variables, the Nomogram risk models of 3 types of cell carcinoma were established, and the discrimination and calibration of the models were evaluated using the Consistency index (C-index) and calibration curves. The C-index of the risk model of renal papillary cell carcinoma was 0.62 (95% CI 0.51 to 1.00, P=0.03). The results of receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) was 0.88. The C-index of the risk model of renal clear cell carcinoma was 0.72 (95% CI 0.52 to 1.00, P=0.03). The results of ROC curve showed that the AUC was 0.90. The C-index of the risk model of chromophobe cell carcinoma of kidney was 0.90 (95% CI 0.85 to 1.00, P<0.01). The results of ROC curve showed that the AUC was 0.59. CONCLUSIONS: GPXs family genes, especially GPX8, are potential markers for poor prognosis of RCC, and the occurrence and development of RCC can be predicted in clinical practice based on the expressions of GPXs family genes.

Icariin ameliorates osteoporosis by activating autophagy in ovariectomized rats.

BACKGROUND: Osteoporosis (OP) is a major problem that increases the mortality and disability rate worldwide. With an increase in the aging population, OP has become a major public threat to human health. Searching for effective and suitable targets for drug treatment in OP has become an urgent need. OBJECTIVES: Osteoporosis is a metabolic bone disease characterized by reduced bone mass and density as well as micro-architectural deterioration. Icariin is a flavonoid extracted from plants of the genus Epimedium and has been shown to exert potential anti-OP activity. The present study was designed to observe the effect of icariin on OP and to clarify the underlying mechanisms in ovariectomized (OVX) rats. MATERIAL AND METHODS: Hematoxylin and eosin (H&E) staining, von Kossa staining and micro-computed tomography (micro-CT) confirmed significant bone loss in the OVX group. Protein expression level was detected with western blot analysis. RESULTS: Icariin reversed a trend of increased bone turnover by reducing serum alkaline phosphatase (ALP), procollagen type I N-terminal propeptide (PINP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), and C-telopeptide of type I collagen (CTX-I). Furthermore, icariin decreased sequestosome 1 (p62) and increased microtubule-associated protein 1 light chain 3II/microtubule-associated protein 1 light chain 3I (LC3II/LC3I), autophagy-related protein 7 (Atg7), and Beclin 1 in the femur of OVX rats, improving the indicators of impaired autophagy in OP. CONCLUSIONS: Icariin reversed the significant upregulation of the serine/threonine protein kinase (Akt), mammalian target of rapamycin (mTOR) and unc-51-like autophagy activating kinase 1 (ULK1) at Ser757, and the downregulation of p-AMP-activated protein kinase (p-AMPK) and ULK1 phosphorylated at Ser555 in the OVX rats, suggesting that the mechanism of icariin action in OP treatment involves the activation and suppression of the AMPK/ULK1 and AKT/mTOR/ULK1 autophagy pathways, respectively.

Selenoprotein GPX3 is a novel prognostic indicator for stomach adenocarcinoma and brain low-grade gliomas: Evidence from an integrative pan-cancer analysis.

Background: The antioxidant enzyme GPX3 is a selenoprotein that transports selenium in blood and maintains its levels in peripheral tissues. Aberrant GPX3 expression is strongly linked to the development of some tumors. However, there is a scarcity of studies examining the pan-cancer expression patterns and prognostic relevance of GPX3. Methods: GPX3 expression levels in normal tissues and multiple tumors were analyzed using TCGA, CCLE, GTEx, UALCAN and HPA databases. Forest plots and KM survival curves were utilized to evaluate the correlation between GPX3 expression and the outcome of tumor patients. The prognostic value of GPX3 in LGG was assessed utilizing the CGGA datasets, and that in STAD was tested by TCGA and GEO databases. A nomogram was then constructed to predict OS in STAD using R software. Additionally, the impact of GPX3 on post-chemoradiotherapy OS in patients with LGG and STAD was evaluated using the KM method. The multiplicative interaction of GPX3 expression, chemotherapy and radiotherapy on STAD and LGG was analyzed using logistic regression models. The correlation of GPX3 with the immune infiltration, immune neoantigens and MMR genes were investigated in TCGA cohort. Results: GPX3 exhibited downregulation across 21 tumor types, including STAD, with its decreased expression significantly associated with improved OS, DFS, PFS and DSS. Conversely, in LGG, low levels of GPX3 expression were indicative of a poorer prognosis. Univariate and multivariate Cox models further identified GPX3 as an independent predictor of STAD, and a nomogram based on GPX3 expression and other independent factors showed high level of predictive accuracy. Moreover, low GPX3 expression and chemotherapy prolonged the survival of STAD. In LGG patients, chemoradiotherapy, GPX3 and chemotherapy, and GPX3 and chemoradiotherapy may improve prognosis. Our observations reveal a notable connection between GPX3 and immune infiltration, immune neoantigens, and MMR genes. Conclusions: The variations in GPX3 expression are linked to the controlling tumor development and could act as a promising biomarker that impacts the prognosis of specific cancers like STAD and LGG.

Dynamic Nomogram for Predicting Long-Term Survival in Terms of Preoperative and Postoperative Radiotherapy Benefits for Advanced Gastric Cancer.

Studies on the prognostic significance of preoperative radiotherapy (PERT) and postoperative radiotherapy (PORT) in patients with advanced gastric cancer (GC) remain elusive. The aim of the study was to evaluate the survival advantage of preoperative and postoperative radiotherapy and construct a dynamic nomogram model to provide customized prediction of the probability of prognostic events for advanced GC patients. We collected clinical records from 2010 to 2015 from the Surveillance, Epidemiology, and End Results (SEER) database with a specific target for stage II-IV GC patients treated with PERT or PORT. We used the least absolute shrinkage and selection operator (LASSO) regression model to identify factors that contribute to the overall survival (OS) of GC patients. The dynamic nomogram infographic was constructed based on the prognostic factors of tumor-specific survival. Out of the 3215 total patients (2271 [70.6%] male; median age, 61 [SD = 12] years), 1204 were in the PERT group and 2011 in the PORT group. Receiving PORT was associated with a survival advantage over PERT for stage II GC patients (HR = 0.791, 95% CI= 0.712-0.879, p < 0.001). The 1-, 3-, and 5-year OS rates were 89.9%, 63.8%, and 53.8% in the PORT group, whereas the corresponding rates were significantly lower in the PERT group (86.4%, 57.1%, and 44.3%, respectively, all p < 0.05). The survival prediction model demonstrated that patients aged > 65 years, with an advanced cancer development stage and tumor size >3 were independent risk factors for poor prognosis (all HR > 1, p < 0.05). In this study, a dynamic nomogram was established based on the LASSO model to provide a statistical basis for the clinical characteristics and predictive factors of advanced GC in a large population. PORT demonstrated significantly better treatment advantages than PERT for stage II GC patients.

Highly Accessible Computational Prediction and In Vivo/In Vitro Experimental Validation: Novel Synthetic Phenyl Ketone Derivatives as Promising Agents against NAFLD via Modulating Oxidoreductase Activity.

Nonalcoholic fatty liver disease (NAFLD) has reached epidemic proportions with no pharmacological treatment approved. Several highly accessible computational tools were employed to predict the activities of twelve novel compounds prior to actual chemical synthesis. We began our work by designing two or three hydroxyl groups appended to the phenyl ketone core, followed by prediction of drug-likeness and targets. Most predicted targets for each compound overlapped with NAFLD targets (≥80%). Enrichment analysis showed that these compounds might regulate oxidoreductase activity. Then, these compounds were synthesized and confirmed by IR, MS, 1H, and 13C NMR. Their cell viability demonstrated that twelve compounds exhibited appreciable potencies against NAFLD (EC50 values ≤ 13.5 µM). Furthermore, the most potent compound 5f effectively prevented NAFLD progression as evidenced by the change in histological features. 5f significantly reduced total cholesterol and triglyceride levels in vitro/in vivo, and the effects of 5f were significantly stronger than those of the control drug. The proteomic data showed that oxidoreductase activity was the most significantly enriched, and this finding was consistent with docking results. In summary, this validated presynthesis prediction approach was cost-saving and worthy of popularization. The novel synthetic phenyl ketone derivative 5f holds great therapeutic potential by modulating oxidoreductase activity to counter NAFLD.

Isolation and Quantification of the Hepatoprotective Flavonoids From Scleromitron diffusum (Willd.) R. J. Wang With Bio-Enzymatic Method Against NAFLD by UPLC-MS/MS.

Flavonoids were the major phytochemicals against hepatic peroxidative injury in Scleromitron diffusum (Willd.) R. J. Wang with an inventive bio-enzymatic method by our group (LU500041). Firstly, the total flavonoids from Scleromitron diffusum (Willd.) R. J. Wang were extracted by reflux, ultrasonic, ultrasound-assisted enzymatic methods (TFH), and the bio-enzymatic method (Ey-TFH). Then 24 flavonoid compounds were isolated and quantified in the extracts by UPLC-MS/MS. Next, six representative differential compounds in Ey-TFH were further screened out by multivariate statistical analysis compared with those in TFH. In a further step, Ey-TFH presented a higher protective rate (59.30 ± 0.81%) against H2O2-damaged HL-02 hepatocytes than TFH. And six representative differential compounds at 8 and 16 µmol/L all exerted significant hepatoprotective effects (p < 0.05 or p < 0.01). Finally, the therapeutic action of Ey-TFH for nonalcoholic fatty liver disease (NAFLD) was processed by a rat's model induced with a high-fat diet. Ey-TFH (90, 120 mg/kg) significantly ameliorated the lipid accumulation in the rat model (p < 0.05). Meanwhile, Ey-TFH relieved liver damage. The levels of ALT, ALP, AST, LDH, and γ-GT in rats' serum were also significantly reduced (p < 0.05 or p < 0.01). In addition to this, the body's antioxidant capacity was improved with elevated SOD and GSH levels (p < 0.05) and down-regulated MDA content (p < 0.01) after Ey-TFH administration. Histopathological observations of staining confirmed the hepatic-protective effect of Ey-TFH.

Galectin-1-Dependent Mitochondria Apoptosis Plays an Essential Role in the Potential Protein Targets of DBDCT-Induced Hepatotoxicity as Revealed by Quantitative Proteomic Analyses.

Di-n-butyl-di-(4-chlorobenzohydroxamato) tin(IV) (DBDCT), a new patent agent, exhibited strong antitumor activity. In some cases, its activity was close to or even higher than cisplatin, a first-line clinical metallic agent. Similar to platinum compounds, it also showed toxicity. However, the effective targets and mechanisms for specific toxicity and biological activity are still unclear. In this study, proteomic analysis revealed that 146 proteins (98 upregulated and 48 downregulated) were differentially identified by label-free LC-MS/MS after DBDCT treatment. Meanwhile, network analysis of these differential proteins suggested that protein Galectin-1 (Gal-1) could regulate the apoptosis process (15 related proteins), which played an essential role in the potential targets of DBDCT-induced hepatotoxicity. Furthermore, it was demonstrated that DBDCT might promote ROS production, activate NF-κB p65, inhibit Ras and p-ERK1/2 expressions, increase the level of Gal-1, subsequently upregulate the expressions of Bax, p53, Fas, and FasL, and downregulate the expression of Bcl-2. As a result of these modulations, caspase cascades were finally activated, which executed apoptosis in HL7702 liver cells. Correspondingly, NAC (inhibitor of ROS), PDTC (inhibitor of NF-κB), EGF (ERK1/2 activator), and OTX008 (inhibitor of Gal-1) were found to reverse and abolish the DBDCT-associated cytotoxicity partially. In conclusion, Gal-1 might be the potential target for toxicity and biological activity. Moreover, the present study will lay the groundwork for future research about di-n-butyl-di-(4-chlorobenzohydroxamato) tin structure optimization and developing it into a new potential anticancer agent.

Mapping of Global Research on Electronic Cigarettes: A Bibliometric Analysis.

Electronic cigarettes (E-cigarettes) use has increased rapidly in the past decades and has been widely studied by scholars worldwide, whereas the research topics and development trends in this field are still unclear. This study aimed to explore the landscape of research relating to e-cigarettes. The data outputted from the Web of Science Core Collection database was used for bibliometric analysis. Frequencies and percentages were used to describe the publications' characteristics. Visualizing maps were designed using VOSviewer 1.6.9 and CiteSpace 5.8 R2. Overall, a total of 7,979 records were identified in the database and the number of researches increased rapidly since 2010. All publications involved 19837 authors, with the top ten authors contributing to 8.71% (695) of all documents. The most productive country and institution were the United States of America and the University of California San Francisco, respectively. Nicotine & Tobacco Research was not only the journal with the most published papers but also the most co-cited journal. The main research domains in this field were the prevalence, awareness, reasons for using e-cigarettes; e-cigarettes use for tobacco harm reduction; exposure in the population; and the relationship between e-cigarettes and tobacco and nicotine. E-cigarettes researches have become a popular field for scholars. The hot topics on e-cigarette research were extensive and changed over the past decade.

Status and potential diagnostic roles of essential trace elements in Kashin- Beck disease patients.

BACKGROUND: This updated and comprehensive meta-analysis study sought to explore the changes of seven essential trace elements, including selenium (Se), iron (Fe), zinc (Zn), manganese (Mn), fluorine (F), iodine (I) and copper (Cu) in Kashin-Beck disease (KBD) patients compared with healthy individuals. The findings of the current study will provide a valuable reference for implementation of early clinical intervention and prevention of KBD. METHODS: All related articles included in this review were retrieved from the following databases: Chinese National Knowledge Infrastructure (CNKI), Wan Fang Data, China Biology Medicine disc (CBM disc), PubMed and Web of Science up to April 30, 2020. The following combination keywords were used as the search criteria: "(Kashin-Beck disease OR KBD) AND ((selenium OR iron OR zinc OR manganese OR fluorine OR iodine OR copper) OR (Se OR Fe OR Zn OR Mn OR F OR I OR Cu))". All statistical analyses were performed using RevMan 5.3 and Stata 16.0 software. RESULTS: A total of 55 articles were included in the current study. Meta-analysis showed that the levels of serum Se (SMD = -2.37, 95 % CI: -1.58 to -0.72, P < 0.00001), hair Se (SMD = -2.19, 95 % CI: -3.05 to -1.33, P < 0.00001), urinary Se (SMD = -2.36, 95 % CI: -3.26 to -1.46, P < 0.00001) and erythrocyte Se (SMD = -5.12, 95 % CI: -9.55 to -0.69, P = 0.02) were significantly lower in KBD patients compared with the levels in healthy controls. Then, the findings showed that the levels of serum F (SMD = -0.58, 95 % CI: -1.04 to -0.12, P = 0.01) and hair I (SMD = -0.57, 95 % CI: -1.06 to -0.08, P = 0.02) in patients were substantially lower than that in controls. Analysis showed that the levels of hair Zn (SMD = 0.26, 95 % CI: 0.04 to 0.49, P = 0.02) and hair Mn (SMD = 0.55, 95 % CI: 0.24 to 0.85, P = 0.0005) were markedly higher in patients compared with the levels in healthy controls. Notably, urinary Se (AUC = 0.7851, P = 0.0235, Sensitivity = 81.82 %, Specificity = 81.82 %) showed a good diagnostic value for KBD. CONCLUSIONS: The findings of the current study showed that the levels of Se, serum F and hair I were lower in patients with KBD compared with those in healthy controls, whereas the levels of hair Zn and hair Mn were higher in KBD patients compared with the levels in controls. This outcome would be further validated in our future studies. Of note, these results indicated that Se, F and I deficiencies were associated with the pathogenesis of KBD.

Selenium concentration is associated with occurrence and diagnosis of three cardiovascular diseases: A systematic review and meta-analysis.

BACKGROUND: Selenium (Se) is a vital trace element playing its biological functions through selenoprotein, which has been implicated in various physiological and pathological processes. A growing number of studies indicate that low Se increases the risk of cardiovascular diseases (CVDs). This meta-analysis aimed to compare and analyze differences in Se levels between patients with heart failure (HF), myocardial infarction (MI), coronary heart disease (CHD), and healthy people. This will provide ideas with the potential to improve clinical intervention and prevention of CVDs. METHODS: The PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI) and Chinese Biomedical databases were systematically searched for relevant publications until November 20, 2020. The following combination keywords were used: "(heart failure disease OR myocardial infarction OR coronary heart disease) AND (selenium OR Se)". The identified studies were screened against inclusion and exclusion criteria and extracted data were analyzed using RevMan5.3 and State 16.0 software. RESULTS: A total of 49 eligible studies (including 61 cohorts) were obtained. Results of the meta-analysis showed that there was a significant difference in Se levels between HF, MI, CHD patients and healthy people. The standard mean difference (SMD) level of Se in HF patients [SMD = -0.98, 95 % CI (-1.34, -0.62)], MI patients [MI: SMD = -3.46, 95 % CI (-4.43, -2.85)], and CHD patients [CHD: SMD = -0.47, 95 % CI (-0.64, -0.28)] were all significantly lower compared to healthy controls. Analysis of the correlation between Se level and publication year showed that SMD of Se levels in HF and controls was positively correlated with time. Se level was found to be a good diagnostic marker of MI (AUC = 0.7107, P = 0.0167, Sensitivity = 77.27 %, Specificity = 72.73 %). CONCLUSIONS: This meta-analysis shows that Se levels in patients with HF, MI, and CHD are generally lower compared with healthy controls. However, due to the small number of included studies, further studies are needed to confirm the present results.

[Urolithin A inhibits inflammation and oxidative stress induced by high lipid in hepatocytes via activating Nrf2 pathway and autophagy].

Objective To investigate the effect and mechanism of urolithin A (UA) on the inflammation and lipid accumulation induced by hyperlipidemia in L02 hepatocytes. Methods Nuclear erythroid 2-related factor 2 (Nrf2) short hairpin RNA (shRNA) lentivirus was used to establish a stable Nrf2 knockdown cell line in L02 cells. Empty vector control cells and Nrf2 knockdown cells were treated with free fatty acids (FFAs) or bovine serum albumin (BSA) to establish the hyperlipidemic cell model, and Urolithin A was treated on this basis. Specifically, they were divided into control group (BSA treatment), FFA treatment group (0.6 mmol/L), FFA (0.6 mmol/L) combined with UA low-dose group (10 µmol/L) and FFA (0.6 mmol/L) combined with UA high-dose group (20 µmol/L). All of these groups were treated for 48 h. The dye of BODIPY493/503 was used to detect the accumulation of lipid droplets in the cell. The levels of triglyceride (TG) was detected by TG assay kit. TNF-α and IL-6 in the supernatant of the cells were detected by ELISA. The level of cellular reactive oxygen species (ROS) was detected by flow cytometry combined with DCFH-DA. Malondialdehyde (MDA) kit was used to test the level of MDA. Total superoxide dismutase (SOD) kit and catalase (CAT) kit were used to detect the activities of total SOD and CAT, respectively. The mRNA levels of SOD2 and CAT were detected by real-time quantitative PCR. The protein levels of SOD2, CAT, Nrf2 as well as P62, LC3 were detected by Western blot analysis. The adenovirus of RFP-GFP-LC3 was used to measure the autophagy flux in the cells. Results FFA increased the levels of TNF-α, IL-6 and TG as well as the positive rate of BODIPY493/503 staining in L02 cells. The levels of MDA and ROS increased, while the mRNA and protein expressions of SOD2, CAT and Nrf2 decreased when treated with FFA. FFA treatment also suppressed the levels of autophagy markers LC33-II and promoted the level of P62, and blocked autophagy flux. UA treatment could reverse the above effects of FFA, with significant difference. When Nrf2 was knocked down, the above effects of UA disappeared. Conclusion Through activating autophagy and antioxidative pathways which are mediated by Nrf2 pathway, urolithin A alleviates inflammation and oxidative stress induced by high lipid in L02 hepatocytes.

Paeonol alleviates lipopolysaccharide­induced hepatocytes injury through alteration of mitochondrial function and NF­κB translocation.

Sepsis is a severe disease, with high mortality. Permanent organ damage caused by sepsis reduces the quality of life of surviving patients. The liver is an easily damaged organ in sepsis and sepsis­associated liver injury foretells a poor prognosis. Unfortunately, there are no effective treatments or drugs to solve this problem. Therefore, strategies or novel drugs are urgently required to protect against liver dysfunction in sepsis. In the present study, lipopolysaccharide (LPS) was used to establish a model of liver injury in vitro. The data demonstrated that pretreatment of L02 human normal hepatocytes with paeonol (PAE) alleviated LPS­induced cell injury and decreased the levels of alanine aminotransferase and aspartate transaminase, indicating a protective effect of PAE. Further experiments demonstrated that PAE increased LPS­decreased L02 cell viability, the levels of superoxide dismutase and Bcl­2 expression. PAE decreased LPS­increased cell apoptosis, intracellular reactive oxygen species and the expression levels of Bax and cleaved­caspase­3. PAE decreased LPS­promoted mitochondrial depolarization and nuclear translocation of NF­κB. In conclusion, PAE alleviated LPS­induced liver injury via alteration of mitochondrial function and NF­κB translocation. Therefore, PAE has potential for the treatment of sepsis.

Traditional Chinese medicine combined with western medicine for the treatment of secondary pulmonary tuberculosis: A PRISMA-compliant meta-analysis.

OBJECTIVE: To evaluate the differences between traditional Chinese medicine combined with western medicine and western medicine alone for the treatment of secondary tuberculosis and its impact on the evaluation of clinical efficacy and safety of patients in randomized controlled trials. METHODS: A literature search of all major academic databases was conducted (PubMed, CNKI, Wanfang, VIP). Meta-analysis was conducted using RevMan 5.3 and Stata 12.0 software for those studies that satisfied the inclusion criteria. Ethical approval was not necessary because no people or animals were selected as subjects in this meta-analysis. RESULTS: Twenty-three randomized controlled trials were included in this meta-analysis. The following indicators in the treatment group (traditional Chinese medicine decoction combined with western medicine chemotherapy) improved in comparison with those in the control group:focus absorption rate (RR:1.18; 95% CI: 1.15-1.22);sputum smear negative rate (RR: 1.17; 95% CI: 1.09-1.27);comprehensive clinical effective rate (RR: 1.18; 95% CI: 1.14-1.22);cavity closure rate (RR: 1.37; 95% CI: 1.12-1.67).The difference of Immune function indicator likes CD4+ level (SMD: 0.76; 95% CI: -0.25 to 1.76) between the treatment group and the control group was not significant. In addition, safety evaluation indicators like the decrease rate of white blood cell (WBC) and platelets (PLT) and the elevation rate of alanine aminotransferase (ALT) and uric acid (UA) in the treatment group were reduced compared with those in the control group (P < .05). CONCLUSIONS: The curative effect of combining traditional Chinese and western medicine for the treatment of secondary tuberculosis is better than that of western medicine alone and is conducive to reducing the incidence of adverse reactions.

Resveratrol alleviates ethanol-induced neuroinflammation in vivo and in vitro: Involvement of TLR2-MyD88-NF-κB pathway.

Excessive ethanol (EtOH) intake affects cognitive function and leads to permanent learning and memory deficits. EtOH-induced neuroinflammation plays an important role in EtOH neurotoxicity. Studies have shown that EtOH activates microglia and induces an inflammatory response. Resveratrol (Rsv) is a natural polyphenol found in a wide variety of plants and fruits, and produces the neuroprotective and anti-inflammatory effects in the central nervous system. However, effect of Rsv on EtOH-induced neuroinflammation is still unknown. We investigated the anti-inflammatory effect of Rsv in the context of EtOH-induced neurotoxicity and the molecular mechanisms potentially involved in the effect. The results showed that treatment of rats with Rsv prevented the deficits of spatial reference memory induced by EtOH and mitigated EtOH-induced neuroinflammation by inhibiting microglial activation and decreasing the levels of inflammatory cytokines including interleukin-1ß, interleukin-6 and tumor necrosis factor α. The further studies indicated that Rsv reduced TLR2 expression in vivo and in vitro, and downregulated expression of myeloid differentiation primary response 88 (MyD88) and phosphorylation of nuclear factor κB (NF-κB). These data demonstrate that Rsv alleviates the ethanol-induced neuroinflammation via inhibition of TLR2-MyD88-NF-κB signal pathway.