Oncogenic transcription factors are known to mediate the conversion of somatic cells to tumour or induced pluripotent stem cells (iPSCs). Here we report c-Jun as a barrier for iPSC formation. c-Jun is expressed by and required for the proliferation of mouse embryonic fibroblasts (MEFs), but not mouse embryonic stem cells (mESCs). Consistently, c-Jun is induced during mESC differentiation, drives mESCs towards the endoderm lineage and completely blocks the generation of iPSCs from MEFs. Mechanistically, c-Jun activates mesenchymal-related genes, broadly suppresses the pluripotent ones, and derails the obligatory mesenchymal to epithelial transition during reprogramming. Furthermore, inhibition of c-Jun by shRNA, dominant-negative c-Jun or Jdp2 enhances reprogramming and replaces Oct4 among the Yamanaka factors. Finally, Jdp2 anchors 5 non-Yamanaka factors (Id1, Jhdm1b, Lrh1, Sall4 and Glis1) to reprogram MEFs into iPSCs. Our studies reveal c-Jun as a guardian of somatic cell fate and its suppression opens the gate to pluripotency.

BackgroundThe association between non-steroidal anti-inflammatory drugs (NSAIDs) and gastric cancer (GC) risk is controversial. The aim of this study is to evaluate the chemopreventive effect of NSAIDs for GC.MethodsA literature search was performed for relevant studies using the PubMed and Embase database (up to March 2016). Risk ratios (RRs) and 95% confidence intervals (CIs) were used as the effect measures. The dose–response analysis and subgroup analysis were also performed.ResultsTwenty-four studies were included. Our results indicated that NSAIDs could reduce GC risk (any NSAIDs: RR=0.78, 96%CI=0.72-0.85; aspirin: RR=0.70, 95%CI=0.62-0.80; non-aspirin NSAIDs: RR=0.86, 95%CI=0.80-0.94), especially for non-cardia GC risk. Moreover, the dose-response analysis indicated the risk of GC decreased by 11% and 5% for 2 years increment of any NSAIDs and aspirin use, respectively. There were nonlinear relationships between the frequency of any NSAIDs use and aspirin use and GC risk (P for non-linearity<0.01), with a threshold effect of 5 times/week. A monotonically decreasing trend was observed only for the frequency of less than 5 times/week.ConclusionsOur results indicate that NSAIDs is inversely associated with GC risk, especially for non-cardia GC risk. NSAIDs use may become a feasible approach to prevent GC.

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AimThe purpose of this study is to assess the associations between periodontal disease, tooth loss and liver diseases.Materials and methodsPubMed and Embase databases were utilized to search eligible studies. Odds ratio (OR) with 95% confidence interval (CI) was used as effect size to assess the associations between periodontal disease, tooth loss and liver diseases risk.ResultsOur results indicated positive associations between periodontal disease and non‐alcoholic fatty liver disease (NAFLD) (OR = 1.19, 95% CI = 1.06–1.33), liver cirrhosis (OR = 2.28, 95% CI = 1.50–3.48) and elevated transaminase level risk (OR = 1.08, 95% CI = 1.02–1.15). Moreover, tooth loss could increase NAFLD (OR = 1.33, 95% CI = 1.12– 1.56) and liver cancer risk (OR = 1.34, 95% CI = 1.04–1.74), and every five increment in tooth loss was associated with 5% increased liver cancer risk (OR = 1.05, 95% CI = 1.01 – 1.10) with a linear relationship. In addition, tooth loss had a positive tendency towards liver cirrhosis risk (OR = 2.03, 95% CI = 0.85–4.85) although there was no statistical significance.ConclusionPeriodontal disease and tooth loss are positively associated with liver diseases including NAFLD, elevated transaminase level, liver cirrhosis and liver cancer.

Coronary artery disease (CAD) is a systemic chronic inflammatory disease, and serum fibrinogen and albumin are 2 important factors in systemic inflammation. We aimed to investigate the relationship between the fibrinogen–albumin ratio (FAR) and outcomes in patients with CAD who underwent percutaneous coronary intervention (PCI). All patients were from the Clinical Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI (CORFCHD-PCI) study, which is a retrospective cohort study (Identifier: ChiCTR-ORC-16010153) that includes a total of 6050 patients with CAD after PCI from January 2008 to December 2016. A total of 5829 patients with CAD after PCI were recruited in the present study. They were divided into 2 groups according to the FAR cutoff value, which was calculated using a receiver operating characteristic curve, a low group (FAR < 0.095, n = 3811), and a high group (FAR ≥ 0.095, n = 2018). The average follow-up time was 35.9 ± 22.6 months. The multivariate Cox proportional hazards model showed that FAR was independently correlated with all-cause mortality (adjusted hazard ratio [HR] = 1.432 [1.134-1.808], P = .003), cardiac mortality (adjusted HR = 1.579 [1.218-2.047], P = .001), major adverse cardiac and cerebrovascular events (adjusted HR = 1.296 [1.125-1.494], P < .001), major adverse cardiac events (adjusted HR = 1.357 [1.170-1.572], P < .001), and heart failure (adjusted HR = 1.540 [1.135-2.091], P = .006). The present study indicated that the FAR was associated with adverse outcomes in patients with CAD who underwent PCI.

Emergence of new viral agents is driven by evolution of interactions between viral proteins and host targets. For instance, increased infectivity of SARS-CoV-2 compared to SARS-CoV-1 arose in part through rapid evolution along the interface between the Spike protein and its human receptor ACE2, leading to increased binding affinity. To facilitate broader exploration of how pathogen-host interactions might impact transmission and virulence in the ongoing COVID-19 pandemic, we performed state-of-the-art interface prediction followed by molecular docking to construct a 3D structural interactome between SARS-CoV-2 and human. We additionally carried out downstream meta-analyses to investigate enrichment of sequence divergence between SARS-CoV-1 and SARS-CoV-2 or human population variants along viral-human protein interaction interfaces, predict changes in binding affinity by these mutations/variants, and further prioritize drug repurposing candidates predicted to competitively bind human targets. We believe this resource ( http://3D-SARS2.yulab.org ) will aid in development and testing of informed hypotheses for SARS-CoV-2 etiology and treatments.

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Hand-foot syndrome (HFS) is the most common adverse effect of capecitabine-containing chemotherapy. The purpose of this study was to assess the efficacies of various prevention and treatment strategies for capecitabine-induced HFS. Searches of the PubMed and Embase databases were performed to identify relevant studies. The risk ratio (RR) with the corresponding 95% confidence interval (CI) was used as an effect measure to evaluate the efficacies of these prevention and treatment strategies. Publication bias was evaluated using Begg's and Egger's tests. Overall and subgroup analyses were conducted. All statistical analyses were conducted with Stata software version 12.0. Seventeen eligible studies were included. Our results indicated that celecoxib was significantly associated with a lower incidence of grade ≥2 capecitabine-induced HFS without heterogeneity (RR = 0.43, 95% CI = 0.23-0.81, I = 0.0%). However, pyridoxine and topical urea/lactic acid were not effective toward preventing capecitabine-induced grade 1, 2, 3, ≥1 or ≥2 HFS. Moreover, pyridoxine was not effective in treating capecitabine-induced HFS. Similar results were obtained by subgroup analysis. Our results indicate that celecoxib has potential prophylactic efficacy for capecitabine-induced HFS. However, pyridoxine and topical urea/lactic acid are not associated with a decrease in the incidence of capecitabine-induced HFS.