Explore the vast range of titles available.

We performed this review to clarify which dietary and lifestyle factors are related to gastroesophageal reflux disease. Through a systematic search of the PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Chinese BioMedical Literature (CBM) databases, we identified articles with clear definitions of GERD, including nonerosive gastroesophageal reflux disease (NERD), reflux esophagitis (RE) and Barrett's esophagus (BE), that included dietary and lifestyle factors as independent factors affecting the onset of GERD (expressed as odds ratios (ORs) or relative risks (RRs) and 95% confidence intervals (CIs)). Due to heterogeneity among the studies, we used descriptive statistical analyses to analyze and synthesize each outcome based on the disease type. In total, 72 articles were included, conducted in ten Western countries (26 articles in total) and nine Eastern countries (46 articles in total). We categorized dietary factors into 20 items and lifestyle factors into 11 items. GERD is related to many irregular dietary and lifestyle habits (such as a habit of midnight snacking: OR=5.08, 95% CI 4.03-6.4; skipping breakfast: OR=2.7, 95% CI 2.17-3.35; eating quickly: OR=4.06, 95% CI 3.11-5.29; eating very hot foods: OR=1.81, 95% CI 1.37-2.4; and eating beyond fullness: OR=2.85, 95% CI 2.18-3.73). Vegetarian diets (consumption of nonvegetarian food (no/yes); OR=0.34, 95% CI 0.211-0.545) and no intake of meat (OR=0.841, 95% CI 0.715-0.990) were negatively related to GERD, while meat (daily meat, fish, and egg intake: OR=1.088, 95% CI 1.042-1.135) and fat (high-fat diet: OR=7.568, 95% CI 4.557-8.908) consumption were positively related to GERD. An interval of less than three hours between dinner and bedtime (OR=7.45, 95% CI 3.38-16.4) was positively related to GERD, and proper physical exercise (physical exercise >30 minutes (>3 times/week): OR=0.7, 95% CI 0.6-0.9) was negatively correlated with GERD. Smoking (OR=1.19, 95% CI 1.12-1.264), alcohol consumption (OR=1.278, 95% CI 1.207-1.353) and mental state (poor mental state: OR=1.278, 95% CI 1.207-1.353) were positively correlated with GERD. RE (vitamin C: OR=0.46, 95% CI=0.24-0.90) and BE (vitamin C: OR=0.44,95% CI 0.2-0.98; vitamin E: OR=0.46, 95% CI 0.26-0.83) were generally negatively correlated with antioxidant intake. In conclusion, many dietary and lifestyle factors affect the onset of GERD, and these factors differ among regions and disease types. These findings need to be further confirmed in subsequent studies.

Sijunzi decoction (SJZD) was used to treat patients with colorectal cancer (CRC) as an adjuvant method. The aim of the study was to investigate the therapeutic targets and pathways of SJZD towards the tumor microenvironment of CRC via network pharmacology and the ESTIMATE algorithm. The ESTIMATE algorithm was used to calculate immune and stromal scores to predict the level of infiltrating immune and stromal cells. The active targets of SJZD were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and UniProt database. The core targets were obtained by matching the differentially expressed genes in CRC tissues and the targets of SJZD. Then, GO, KEGG and validation in TCGA were carried out. According to the ESTIMATE algorithm and survival analysis, the median survival time of the low stromal score group was significantly higher than that of the high stromal score group (P = 0.018), while the patients showed no significant difference of OS between different immune groups (P = 0.19). A total of 929 genes were upregulated and 115 genes were downregulated between the stromal score groups (|logFC| > 2, adjusted P < 0.05); 357 genes were upregulated and 472 genes were downregulated between the immune score groups. The component-target network included 139 active components and 52 related targets. The core targets were HSPB1, SPP1, IGFBP3, and TGFB1, which were significantly associated with poor prognosis in TCGA validation. GO terms included the response to hypoxia, the extracellular space, protein binding and the TNF signaling pathway. Immunoreaction was the main enriched pathway identified by KEGG analysis. The core genes (HSPB1, SPP1, IGFBP3 and TGFB1) affected CRC development and prognosis by regulating hypoxia, protein binding and epithelial-mesenchymal transition in the extracellular matrix.

Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma originating in the skin. Studies are needed to determine the mechanisms of immune escape in patients with MCC, and malignant cell conditions that promote immune evasion. We used Single-cell RNA sequencing (scRNA-seq) to determine cellular features associated with MCC disease trajectory. A longitudinal multi-omics study was performed using scRNA-seq data of peripheral blood harvested from four-time points. Six major cell types and fifteen cell subgroups were identified and confirmed their presence by expression of characteristic markers. The expression patterns and specific changes of different cells at different time points were investigated. Subsequently, bulk RNA data was used to validate key findings. The dynamic characteristics of the cells were identified during the critical period between benign improvement and acquisition of resistance. Combined with the results of the validation cohort, the resistance program expressed in the relapse stage is mainly associated with T cell exhaustion and immune cell crosstalk disorder. Coinciding with immune escape, we also identified a decrease non-classical monocytes and an expansion of classical monocytes with features of high inflammation and immune deficiency. Changes in cellular status, such as depletion of T cells and dysregulation of B cell proliferation and differentiation, may lead to drug resistance in MCC patients. Meanwhile, the widespread decreased antigen presentation ability and immune disorders caused by deletion of MHC class II gene expression should not be ignored.

Background This review aims to critically appraise and compare the measurement properties of inflammatory bowel disease (IBD)-specific health-related quality of life instruments. Methods Medline, EMBASE and ISI Web of Knowledge were searched from their inception to May 2016. IBD-specific instruments for patients with Crohn’s disease, ulcerative colitis or IBD were enrolled. The basic characteristics and domains of the instruments were collected. The methodological quality of measurement properties and measurement properties of the instruments were assessed. Results Fifteen IBD-specific instruments were included, which included twelve instruments for adult IBD patients and three for paediatric IBD patients. All of the instruments were developed in North American and European countries. The following common domains were identified: IBD-related symptoms, physical, emotional and social domain. The methodological quality was satisfactory for content validity; fair in internal consistency, reliability, structural validity, hypotheses testing and criterion validity; and poor in measurement error, cross-cultural validity and responsiveness. For adult IBD patients, the IBDQ-32 and its short version (SIBDQ) had good measurement properties and were the most widely used worldwide. For paediatric IBD patients, the IMPACT-III had good measurement properties and had more translated versions. Conclusions Most methodological quality should be promoted, especially measurement error, cross-cultural validity and responsiveness. The IBDQ-32 was the most widely used instrument with good reliability and validity, followed by the SIBDQ and IMPACT-III. Further validation studies are necessary to support the use of other instruments.

Banxia Houpu decoction (BXHPD) has been used to treat depression in clinical practice for centuries. However, the pharmacological mechanisms of BXHPD still remain unclear. Network Pharmacology (NP) approach was used to explore the potential molecular mechanisms of BXHPD in treating depression. Potential active compounds of BXHPD were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform Database. STRING database was used to build a interaction network between the active compounds and target genes associated with depression. The topological features of nodes were visualized and calculated. Significant pathways and biological functions were identified using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. A total of 44 active compounds were obtained from BXHPD, and 121 potential target genes were considered to be therapeutically relevant. Pathway analysis indicated that MAPK signaling pathway, ErbB signaling pathway, HIF-1 signaling pathway and PI3K-Akt pathway were significant pathways in depression. They were mainly involved in promoting nerve growth and nutrition and alleviating neuroinflammatory conditions. The result provided some potential ways for modern medicine in the treatment of depression.

There were no systematic researches about autophagy-related long noncoding RNA (lncRNA) signatures to predict the survival of patients with colon adenocarcinoma. It was necessary to set up corresponding autophagy-related lncRNA signatures. The expression profiles of lncRNAs which contained 480 colon adenocarcinoma samples were obtained from The Cancer Genome Atlas (TCGA) database. The coexpression network of lncRNAs and autophagy-related genes was utilized to select autophagy-related lncRNAs. The lncRNAs were further screened using univariate Cox regression. In addition, Lasso regression and multivariate Cox regression were used to develop an autophagy-related lncRNA signature. A risk score based on the signature was established, and Cox regression was used to test whether it was an independent prognostic factor. The functional enrichment of autophagy-related lncRNAs was visualized using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Ten prognostic autophagy-related lncRNAs (AC027307.2, AC068580.3, AL138756.1, CD27-AS1, EIF3J-DT, LINC01011, LINC01063, LINC02381, AC073896.3, and SNHG16) were identified to be significantly different, which made up an autophagy-related lncRNA signature. The signature divided patients with colon adenocarcinoma into the low-risk group and the high-risk group. A risk score based on the signature was a significantly independent factor for the patients with colon adenocarcinoma (HR=1.088, 95%CI=1.057−1.120; P<0.001). Additionally, the ten lncRNAs were significantly enriched in autophagy process, metabolism, and tumor classical pathways. In conclusion, the ten autophagy-related lncRNAs and their signature might be molecular biomarkers and therapeutic targets for the patients with colon adenocarcinoma.

Background To investigate the association of four insulin resistance (IR) indicators with hepatic steatosis and fibrosis in patients with metabolic syndrome (MetS), as well as to compare the diagnostic value of these indicators in identifying hepatic steatosis and fibrosis in individuals with MetS. Methods This cross-sectional study used the data from the National Health and Nutrition Examination Survey 2017–2018. IR indicators included homeostasis model assessment of IR (HOMA-IR), triglyceride/glucose (TyG) index, triglyceride glucose-waist-to-height ratio (TyG-WHtR), and metabolic score for IR (METS-IR). The main endpoints of this study were hepatic steatosis and hepatic fibrosis. Weighted univariate and multivariate logistic regression models were employed to evaluate the association between four IR indicators and both hepatic steatosis, hepatic fibrosis. The efficacy of various IR indicators in the detection of hepatic steatosis and hepatic fibrosis were assessed using receiver operating characteristics curve (ROC). Results A total of 876 participants with MetS were enrolled. Among the participants, hepatic steatosis was observed in 587 MetS individuals, while hepatic fibrosis was identified in 151 MetS individuals. In multivariate logistic regression model, HOMA-IR, TyG, TyG-WHtR, and METS-IR were related to the increased odd of hepatic steatosis. Additionally, HOMA-IR, TyG-WHtR, and METS-IR were associated with increased odd of hepatic fibrosis. According to the ROC analysis, the area under the curve (AUC) of the TyG-WHtR (AUC = 0.705, 95%CI: 0.668–0.743) was higher than HOMA-IR (AUC = 0.693, 95%CI: 0.656–0.730), TyG (AUC = 0.627, 95%CI: 0.587–0.666), and METS-IR (AUC = 0.685, 95%CI: 0.648–0.722) for identifying hepatic steatosis of MetS patients. Likewise, TyG-WHtR was also higher than HOMA-IR, TyG, and METS-IR for identifying hepatic fibrosis of MetS patients. Conclusion HOMA-IR, TyG-WHtR, and METS-IR may be associated with the risk of hepatic steatosis and fibrosis among the U.S. adult population with MetS. In addition, TyG-WHtR may have a good predictive value for hepatic steatosis and hepatic fibrosis.

Anemarrhena asphodeloides Bunge is a famous Chinese Materia Medica and has been used in traditional Chinese medicine for more than two thousand years. Steroidal saponins are important active components isolated from A. asphodeloides Bunge. Among which, the accumulation of numerous experimental studies involved in Timosaponin AIII (Timo AIII) draws our attention in the recent decades. In this review, we searched all the scientific literatures using the key word “timosaponin AIII” in the PubMed database update to March 2020. We comprehensively summarized the pharmacological activity, pharmacokinetics, and toxicity of Timo AIII. We found that Timo AIII presents multiple-pharmacological activities, such as anti-cancer, anti-neuronal disorders, anti-inflammation, anti-coagulant, and so on. And the anti-cancer effect of Timo AIII in various cancers, especially hepatocellular cancer and breast cancer, is supposed as its most potential activity. The anti-inflammatory activity of Timo AIII is also beneficial to many diseases. Moreover, VEGFR, X-linked inhibitor of apoptosis protein (XIAP), B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1), thromboxane (Tx) A2 receptor, mTOR, NF-κB, COX-2, MMPs, acetylcholinesterase (AChE), and so on are identified as the crucial pharmacological targets of Timo AIII. Furthermore, the hepatotoxicity of Timo AIII was most concerned, and the pharmacokinetics and toxicity of Timo AIII need further studies in diverse animal models. In conclusion, Timo AIII is potent as a compound or leading compound for further drug development while still needs in-depth studies.

The environmental and health risks of silver nanoparticles (AgNPs) have driven the development of numerous engineering strategies to reduce the likelihood of exposure. Nonetheless, AgNP exposure is often inevitable, prompting a search for effective detoxification strategies at the organism level. Given the critical role of the gut microbiota in host health, we test its ability to mitigate the adverse effects of AgNPs by introducing various bacterial strains into the Caenorhabditis elegans gut and then comparing the nematode’s response with that of germ-free nematodes. Reproduction, the most sensitive toxicity endpoint tested herein, is significantly impaired by AgNPs but is rescued by colonization with Pseudomonas mendocina . Gene expression analyses reveal that this bacterium suppresses both the initiating and key events within the adverse outcome pathways triggered by AgNPs. Metabolomic profiling of gut bacteria and AgNP-exposed nematodes followed by verification with standard substances identifies two thiamine-derived metabolites, 4-methyl-5-thiazoleethanol and thiamine monophosphate, as pivotal in reducing the reproductive toxicity of AgNPs. Our study presents a promising approach to mitigate the adverse effects of nanoparticle exposure, through manipulation of the gut microbiota. Silver nanoparticles are used in a wide range of applications but have potential toxicity issues. Here, the authors report on a gut bacterium which can protect nematodes from reproductive harm caused by silver nanoparticles via the production of protective metabolites showing a strategy for mitigating nanoparticle toxicity.

Background Thymosin β4 (Tβ4) is the most abundant member of the β-thymosins and plays an important role in the control of actin polymerization in eukaryotic cells. While its effects in multiple organs and diseases are being widely investigated, the safety profile has been established in animals and humans, currently, little is known about its influence on Alzheimer’s disease (AD) and the possible mechanisms. Thus, we aimed to evaluate the effects and mechanisms of Tβ4 on glial polarization and cognitive performance in APP/PS1 transgenic mice. Methods Behavior tests were conducted to assess the learning and memory, anxiety and depression in APP/PS1 mice. Thioflavin S staining, Nissl staining, immunohistochemistry/immunofluorescence, ELISA, qRT-PCR, and immunoblotting were performed to explore Aβ accumulation, phenotypic polarization of glial cells, neuronal loss and function, and TLR4/NF-κB axis in APP/PS1 mice. Results We demonstrated that Tβ4 protein level elevated in all APP/PS1 mice. Over-expression of Tβ4 alone alleviated AD-like phenotypes of APP/PS1 mice, showed less brain Aβ accumulation and more Insulin-degrading enzyme (IDE), reversed phenotypic polarization of microglia and astrocyte to a healthy state, improved neuronal function and cognitive behavior performance, and accidentally displayed antidepressant-like effect. Besides, Tβ4 could downregulate both TLR4/MyD88/NF-κB p65 and p52-dependent inflammatory pathways in the APP/PS1 mice. While combination drug of TLR4 antagonist TAK242 or NF-κB p65 inhibitor PDTC exerted no further effects. Conclusions These results suggest that Tβ4 may exert its function by regulating both classical and non-canonical NF-κB signaling and is restoring its function as a potential therapeutic target against AD.