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2,849 result(s) for "Shen, Shan"
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Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients
Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly conserved protease which is indispensable for CoVs replication, and is a promising target for development of broad-spectrum antiviral drugs. In this study we investigated the anti-SARS-CoV-2 potential of Shuanghuanglian preparation, a Chinese traditional patent medicine with a long history for treating respiratory tract infection in China. We showed that either the oral liquid of Shuanghuanglian, the lyophilized powder of Shuanghuanglian for injection or their bioactive components dose-dependently inhibited SARS-CoV-2 3CLpro as well as the replication of SARS-CoV-2 in Vero E6 cells. Baicalin and baicalein, two ingredients of Shuanghuanglian, were characterized as the first noncovalent, nonpeptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography was distinctly different from those of known 3CLpro inhibitors. Baicalein was productively ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a “shield” in front of the catalytic dyad to effectively prevent substrate access to the catalytic dyad within the active site. Overall, this study provides an example for exploring the in vitro potency of Chinese traditional patent medicines and effectively identifying bioactive ingredients toward a specific target, and gains evidence supporting the in vivo studies of Shuanghuanglian oral liquid as well as two natural products for COVID-19 treatment.
Management of gastric cancer in Asia: resource-stratified guidelines
Gastric cancer is the fourth most common cancer globally, and is the second most common cause of death from cancer worldwide. About three-quarters of newly diagnosed cases in 2008 were from Asian countries. With a high mortality-to-incidence ratio, management of gastric cancer is challenging. We discuss evidence for optimum management of gastric cancer in aspects of screening and early detection, diagnosis, and staging; endoscopic and surgical intervention; and the concepts of perioperative, postoperative, and palliative chemotherapy and use of molecularly targeted therapy. Recommendations are formulated on the basis of the framework provided by the Breast Health Global Initiative, using the categories of basic, limited, enhanced, and maximum level. We aim to provide a stepwise strategy for management of gastric cancer applicable to different levels of health-care resources in Asian countries.
Transcriptional reprogramming in oral squamous cell carcinoma
Oral squamous cell carcinoma (OSCC) is a prevalent form of cancer globally. This disease is characterized by its complex genetic underpinnings, involving the intricate regulation of multiple genes. Genetic factors influence cellular processes such as growth, differentiation, and apoptosis of oral mucosal cells, thereby promoting or inhibiting tumor formation and progression. Furthermore, environmental factors—including smoking, alcohol consumption, and human papillomavirus (HPV) infection—can significantly increase the risk of developing OSCC. These external influences can impact the disease in several ways. Delayed clinical detection and the absence of specific biomarkers, coupled with expensive treatment alternatives, contribute to poor prognoses among OSCC patients. Thus, identifying OSCC biomarkers has become imperative. This study investigates publicly accessible sequencing data of oral mucosal tissues from four distinct datasets—GSE23558, GSE30784, GSE36090, and GSE51010—archived in the Gene Expression Omnibus (GEO) database. By analyzing these datasets, which encompass a range of genetic profiles and experimental conditions, the study seeks to uncover critical biomarkers and molecular pathways involved in the early stages of OSCC development. The primary objective is to identify pivotal genes linked to the onset of OSCC. The findings provide preliminary evidence for therapeutic targets in OSCC and may serve as a robust foundation for subsequent biological research endeavors.
Dietary Patterns and Pancreatic Cancer Risk: A Meta-Analysis
A number of studies have examined the associations between dietary patterns and pancreatic cancer risk, but the findings have been inconclusive. Herein, we conducted this meta-analysis to assess the associations between dietary patterns and the risk of pancreatic cancer. MEDLINE (provided by the National Library of Medicine) and EBSCO (Elton B. Stephens Company) databases were searched for relevant articles published up to May 2016 that identified common dietary patterns. Thirty-two studies met the inclusion criteria and were finally included in this meta-analysis. A reduced risk of pancreatic cancer was shown for the highest compared with the lowest categories of healthy patterns (odds ratio, OR = 0.86; 95% confidence interval, CI: 0.77–0.95; p = 0.004) and light–moderate drinking patterns (OR = 0.90; 95% CI: 0.83–0.98; p = 0.02). There was evidence of an increased risk for pancreatic cancer in the highest compared with the lowest categories of western-type pattern (OR = 1.24; 95% CI: 1.06–1.45; p = 0.008) and heavy drinking pattern (OR = 1.29; 95% CI: 1.10–1.48; p = 0.002). The results of this meta-analysis demonstrate that healthy and light–moderate drinking patterns may decrease the risk of pancreatic cancer, whereas western-type and heavy drinking patterns may increase the risk of pancreatic cancer. Additional prospective studies are needed to confirm these findings.
Blockade of autophagy reduces pancreatic cancer stem cell activity and potentiates the tumoricidal effect of gemcitabine
Background Cancer stem cells (CSCs) are considered responsible for the recurrence and chemoresistance of cancer. Dysregulated autophagy is highly prevalent in many types of cancer including pancreatic cancer and has been implicated in cytoprotection and tumor promotion. This study aimed to investigate the role of autophagy in regulating cancer stemness and chemoresistance of pancreatic cancer. Methods The correlation between autophagy and CSCs and its clinical significance were analyzed using pancreatic cancer tissue microarrays. Genetic and pharmacological approaches were applied to explore the function of autophagy on CSC activity and gemcitabine resistance of pancreatic cancer cells in vitro and in vivo . Results LC3 expression positively correlated with the expression of CSC markers aldehyde dehydrogenase 1 (ALDH1), CD44, and CD133 in pancreatic cancer tissues. High coexpression of LC3/ALDH1 was associated with both poor overall survival and progression-free survival. In pancreatic cancer cell lines, higher LC3-II expression was observed in the sphere-forming cells than in the bulk cells. Blockade of autophagy by silencing ATG5 , ATG7 , and BECN1 or the administration of autophagy inhibitor chloroquine markedly reduced the CSC populations, ALDH1 activity, sphere formation, and resistance to gemcitabine in vitro and in vivo . Furthermore, osteopontin (OPN) was found to stimulate LC3-II, ALDH1, CD44, and CD133 expression in PANC-1 cells, whereas this effect could be prevented by OPN knockdown and autophagy blockade. After treatment with various inhibitors against the major signaling pathways downstream of OPN, only the inhibitor of NF-κB activation, BAY 1170–82, could effectively counteract OPN-induced autophagy and CSC activity. According to the histochemical results, pancreatic cancer patients manifesting high levels of OPN/LC3/ALDH1 and OPN/CD44/CD133 had poor survival. Conclusions Induction of autophagy mediated by OPN/NF-κB signaling is required for maintenance of pancreatic CSC activity. Combination of gemcitabine with pharmacological autophagy inhibitors is a promising therapeutic strategy for pancreatic cancer.
Layer 4 of mouse neocortex differs in cell types and circuit organization between sensory areas
Layer 4 (L4) of mammalian neocortex plays a crucial role in cortical information processing, yet a complete census of its cell types and connectivity remains elusive. Using whole-cell recordings with morphological recovery, we identified one major excitatory and seven inhibitory types of neurons in L4 of adult mouse visual cortex (V1). Nearly all excitatory neurons were pyramidal and all somatostatin-positive (SOM + ) non-fast-spiking interneurons were Martinotti cells. In contrast, in somatosensory cortex (S1), excitatory neurons were mostly stellate and SOM + interneurons were non-Martinotti. These morphologically distinct SOM + interneurons corresponded to different transcriptomic cell types and were differentially integrated into the local circuit with only S1 neurons receiving local excitatory input. We propose that cell type specific circuit motifs, such as the Martinotti/pyramidal and non-Martinotti/stellate pairs, are used across the cortex as building blocks to assemble cortical circuits. Layer 4 of the mammalian neocortex is important for cortical information processing but its cellular composition and local circuits remains elusive. The authors compared two primary sensory cortical areas of mice and found differences in cell composition and local connectivity.
Transfer learning for accelerated failure time model with microarray data
Background In microarray prognostic studies, researchers aim to identify genes associated with disease progression. However, due to the rarity of certain diseases and the cost of sample collection, researchers often face the challenge of limited sample size, which may prevent accurate estimation and risk assessment. This challenge necessitates methods that can leverage information from external data (i.e., source cohorts) to improve gene selection and risk assessment based on the current sample (i.e., target cohort). Method We propose a transfer learning method for the accelerated failure time (AFT) model to enhance the fit on the target cohort by adaptively borrowing information from the source cohorts. We use a Leave-One-Out cross validation based procedure to evaluate the relative stability of selected genes and overall predictive power. Conclusion In simulation studies, the transfer learning method for the AFT model can correctly identify a small number of genes, its estimation error is smaller than the estimation error obtained without using the source cohorts. Furthermore, the proposed method demonstrates satisfactory accuracy and robustness in addressing heterogeneity across the cohorts compared to the method that directly combines the target and the source cohorts in the AFT model. We analyze the GSE88770 and GSE25055 data using the proposed method. The selected genes are relatively stable, and the proposed method can make an overall satisfactory risk prediction.
Effects of liraglutide, metformin and gliclazide on body composition in patients with both type 2 diabetes and non‐alcoholic fatty liver disease: A randomized trial
Aims/Introduction To compare the effects of gliclazide, liraglutide and metformin on body composition in patients with type 2 diabetes mellitus with non‐alcoholic fatty liver disease. Materials and Methods A total of 85 patients were randomly allocated to receive gliclazide (n = 27), liraglutide (n = 29) or metformin (n = 29) monotherapy for 24 weeks. Body composition was measured using dual‐energy X‐ray absorptiometry. Results Liraglutide and metformin reduced total, trunk, limb, android and gynoid fat mass; this also led to weight reduction. However, gliclazide treatment produced no significant changes in weight or fat mass, likely because reductions in fat mass were concomitant with increases in lean tissue mass. Blood glucose concentrations and glycated hemoglobin levels improved in all treatment arms; levels of the latter were lower in patients treated with liraglutide and metformin. Serum alanine aminotransferase concentrations decreased in all treatment arms, whereas serum aspartate aminotransferase concentrations were reduced only by liraglutide and metformin. In all patients, weight loss and total, trunk, limb, and android fat mass reductions were positively correlated with decreases in serum alanine aminotransferase and aspartate aminotransferase levels, whereas reductions in waist circumference were positively correlated with lower serum alanine aminotransferase levels. Conclusions Compared with gliclazide, liraglutide and metformin monotherapies result in greater weight loss, reductions in body fat mass, and better blood glucose control among type 2 diabetes mellitus patients with non‐alcoholic fatty liver disease. Reductions in weight, fat mass and waist circumference favorably affect hepatic function. This single‐center, open‐label, prospective, randomized clinical trial examined the effect of liraglutide, metformin, and gliclazide on body composition in patients with type 2 diabetes and concomitant non‐alcoholic fatty liver disease. The results show that liraglutide and metformin are superior to gliclazide in terms of reducing body weight, body mass index, and body fat mass, and in terms of improving liver function and glycosylated hemoglobin levels. In addition, liraglutide and metformin were shown to reduce fat mass rather than lean tissue mass, which is helpful in improving the body weight and glycemic control. Weight remained stable in the gliclazide group; this resulted from identical reductions in fat mass and increases in lean tissue mass.
An updated analysis of the epidemiologic trends of neuroendocrine tumors in Taiwan
The incidence of neuroendocrine tumors (NETs) has been increasing in recent decades. Previously, we reported the incidence and survival of NETs in Taiwan by analyzing the 1996–2008 data from the Taiwan Cancer Registry. Here we performed an updated analysis on the incidence and survival of NETs in Taiwan from 1996 to 2015. The incidence of NETs was 0.244 per 100,000 in 1996 and increased to 3.162 per 100,000 in 2015. The most common site of NETs was rectum (29.65%), followed by lung/bronchus (17.22%), and pancreas (10.71%). The 5- and 10-year overall survival rates of all NETs were 54.6% and 45.3%, respectively. Female and younger NETs patients had a better survival. The survival of all NETs diagnosed between 2010 and 2015 was better than those diagnosed between 2004 and 2009. Among the common sites of NETs, an improved survival of pancreatic NETs diagnosed between 2010 and 2015 compared to those diagnosed between 2004 and 2009 was observed. Overall, the incidence of NETs in Taiwan has continued to increase. The survival of pancreatic NET has shown a recent improvement. The development of novel therapeutic agents has the potential to improve the prognosis of NETs of other sites in the near future.