Induced pluripotent stem (iPS) cells, especially those reprogrammed from patient somatic cells, have a great potential usage in regenerative medicine. The expression of p53 has been proven as a key barrier limiting iPS cell generation, but how p53 is regulated during cell reprogramming remains unclear. In this study, we found that the ectopic expression of miR-138 significantly improved the efficiency of iPS cell generation via Oct4, Sox2, and Klf4, with or without c-Myc (named as OSKM or OSK, respectively), without sacrificing the pluripotent characteristics of the generated iPS cells. Exploration of the mechanism showed that miR-138 directly targeted the 3 0 untranslated region (UTR) of p53, significantly decreasing the expression of p53 and its downstream genes. Furthermore, the ectopic expression of p53 having a mutant 3 0 -UTR, which cannot be bound by miR-138, seriously impaired the effect of miR-138 on p53 signaling and OSKM-initiated somatic cell reprogramming. Combined with the fact that miR-138 is endogenously expressed in fibroblasts, iPS cells, and embryonic stem cells, our study demonstrated that regulation of the p53 signaling pathway and promotion of iPS cell generation represent an unrevealed important function of

Background The coronavirus disease 2019 (COVID‐19) pandemic is a worldwide crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Many COVID‐19 patients present with fever in the early phase, with some progressing to a hyperinflammatory phase. Ethanol (EtOH) exposure may lead to systemic inflammation. Network meta‐analysis was conducted to examine possible relationships between EtOH consumption and COVID‐19 pathologies. Methods Molecules affected by EtOH exposure were identified by analysis with QIAGEN Knowledge Base. Molecules affected by COVID‐19 were identified from studies in MEDLINE, bioRxiv, and medRxiv reporting gene expression profiles in COVID‐19 patients, QIAGEN Coronavirus Network Explorer, and analysis of the RNA‐sequencing data of autopsied lungs of COVID‐19 patients retrieved from the GEO database. Network meta‐analysis was then conducted on these molecules using QIAGEN Ingenuity Pathway Analysis (IPA). Results Twenty‐eight studies reporting significant gene expression changes in COVID‐19 patients were identified. One RNA‐sequencing dataset on autopsied lungs of COVID‐19 patients was retrieved from GEO. Our network meta‐analysis suggests that EtOH exposure may augment the effects of SARS‐CoV‐2 infection on hepatic fibrosis signaling pathway, cellular metabolism and homeostasis, inflammation, and neuroinflammation. EtOH may also enhance the activity of key mediators including cytokines, such as IL‐1β, IL‐6, and TNF, and transcription factors, such as JUN and STAT, while inhibiting the activity of anti‐inflammatory mediators including glucocorticoid receptor. Furthermore, IL‐1β, IL‐6, TNF, JUN, and STAT were mapped to 10 pathways predicted to associate with SARS‐CoV‐2 proteins, including HMGB1, IL‐1, and IL‐6 signaling pathways. Conclusions Our meta‐analyses demonstrate that EtOH exposure may augment SARS‐CoV‐2–induced inflammation by altering the activity of key inflammatory mediators. Our findings suggest that it is important for clinicians to caution patients about the risk of alcohol consumption, which has increased during the COVID‐19 pandemic. The findings also call for further investigation into how alcohol exposure affects viral infections.

Gliomas display cellular hierarchies with self-renewing tumorigenic glioma stem cells (GSCs) at the apex. The GSC niches function as a regulator of GSC maintenance, however, the exact components of GSC niches that mediate this process are still far from fully defined. Here, we showed that glioma cells with aberrant mesenchymal phenotypes constitute a mesenchymal niche for GSCs. Using patient-derived specimens, we demonstrated that the paracrine PGI signaling, initiated by mesenchymal glioma cells, induces the self-renewal and tumorigenic potentials of GSCs through induction of KLF4. Treatment of intracranial orthotopic xenografts with shPGI or shKLF4 leads to less lethal potency. Our data therefore suggest that blockade of the PGI-KLF4 pathway may provide a therapeutic strategy against GSC niches.

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