Hinsonmckinnon2415

Use of the rat SCI models showed that miR-135a-5p could increase the Basso, Beattie, and Bresnahan (BBB) scores, indicating neurological function recovery. In conclusion, the miR-135a-5p-SP1-Bax/Bcl-2/caspase-3 and miR-135a-5p-ROCK-AKT/GSK3β axes are involved in functional recovery of SCI by regulating neural apoptosis and axon regeneration, respectively, and thus can be promising effective therapeutic strategies in SCI.MicroRNA 22 (miR-22) was found in diverse cardiovascular diseases to have a role in regulating multiple cellular processes. However, the regulatory role of miR-22 in aortic dissection (AD) was still unclear. The miR-22 expression in human aorta was explored. Alpelisib in vivo A series of mimic, inhibitor, or small interfering RNA (siRNA) plasmids were delivered into vascular smooth muscle cells (VSMCs) to explore the effects of miR-22 and p38 mitogen-activated protein kinase α (p38MAPKα) in controlling VSMC apoptosis in vitro. In addition, a mouse AD model was established, and histopathologic analyses were performed to evaluate the regulatory effects of miR-22. Reduced miR-22 and increased apoptosis of VSMCs was seen in human AD aorta. Downregulation of miR-22 increased the apoptosis of VSMCs in vitro. Bioinformatics analyses revealed that p38MAPKα was a target of miR-22. Inhibiting p38MAPKα expression could reverse the apoptosis of VSMCs induced by miR-22 downregulation. Knockdown of miR-22 in the AD mouse model significantly promoted the development of AD. Our data underscore the importance of vascular remodeling and VSMC function in AD. miR-22 may represent a new therapeutic approach for AD by regulating the apoptosis of VSMCs through the MAPK signaling pathway.Transcription factors play key roles in cell-fate decisions by regulating 3D genome conformation and gene expression. The traditional view is that methylation of DNA hinders transcription factors binding to them, but recent research has shown that many transcription factors prefer to bind to methylated DNA. Therefore, identifying such transcription factors and understanding their functions is a stepping-stone for studying methylation-mediated biological processes. In this paper, a two-step discriminated method was proposed to recognize transcription factors and their preference for methylated DNA based only on sequences information. In the first step, the proposed model was used to discriminate transcription factors from non-transcription factors. The areas under the curve (AUCs) are 0.9183 and 0.9116, respectively, for the 5-fold cross-validation test and independent dataset test. Subsequently, for the classification of transcription factors that prefer methylated DNA and transcription factors that prefer non-methylated DNA, our model could produce the AUCs of 0.7744 and 0.7356, respectively, for the 5-fold cross-validation test and independent dataset test. Based on the proposed model, a user-friendly web server called TFPred was built, which can be freely accessed at http//lin-group.cn/server/TFPred/.[This corrects the article DOI 10.1038/mtna.2016.46.].Adult cardiac hypoxia as a crucial pathogenesis factor can induce detrimental effects on cardiac injury and dysfunction. The global transcriptome and translatome reflecting the cellular response to hypoxia have not yet been extensively studied in myocardium. In this study, we conducted RNA sequencing (RNA-seq) and ribosome profiling technique (polyribo-seq) in rat heart tissues and H9C2 cells exposed to different periods of hypoxia stress in vivo and in vitro. The temporal gene-expression profiling displayed the distinction of transcriptome and translatome, which were mainly concentrated in cell apoptosis, autophagy, DNA repair, angiogenesis, vascular process, and cardiac cell proliferation and differentiation. A large number of genes such as GNAI3, SEPT4, FANCL, BNIP3, TBX3, ESR2, PTGS2, KLF4, and ADRB2, whose transcript and translation levels are closely correlated, were identified to own a common RNA motif "5'-GAAGCUGCC-3'" in 5' UTR. NCBP3 was further determined to recognize this RNA motif and facilitate translational process in myocardium under hypoxia stress. Taken together, our data show the close connection between alterations of transcriptome and translatome after hypoxia exposure, emphasizing the significance of translational regulation in related studies. The profiled molecular responses in current study may be valuable resources for advanced understanding of the mechanisms underlying hypoxia-induced effect on heart diseases.Trophoblast stem cells (TSCs) have been confirmed to play a cardioprotective role in heart failure. However, whether TSC-derived exosomes (TSC-exos) can protect against cardiac injury remains unclear. In the present study, TSC-exos were isolated from the supernatant of TSCs using the ultracentrifugation method and characterized by transmission electron microscopy and western blotting. Utilizing the public Gene Expression Omnibus (GEO) database, we found that let-7i and Yes-associated protein 1 (YAP) could participate in the development of heart failure. In vitro, AC16 cardiomyocytes subjected to doxorubicin (DOX) were treated with TSC-exos or let-7i mimic. Flow cytometry showed that TSC-exos and let-7i both decreased cardiomyocyte apoptosis. In vivo, mice that were intraperitoneally injected into DOX received either PBS, TSC-exos, or AAV9-let7iup for let-7i overexpression. Mice receiving TSC-exos and AAV9-let7iup showed improved cardiac function and decreased inflammatory responses, accompanied by downregulated YAP signaling. Mechanistically, TSC-exos could transfer let-7i to cardiomyocytes and silence the YAP signaling pathway. In conclusion, TSC-exos could alleviate DOX-induced cardiac injury via the let-7i/YAP pathway, which sheds new light on the application of TSC-exos as a potential therapeutic tool for heart failure.Objective  The Chicago area is known to harbor some of the deepest racial and ethnic socioeconomic inequalities in the United States. We studied the prevalence and neighborhood distribution of patients who tested positive for COVID-19 after implementation of universal screening at an academic hospital providing obstetrical services to an underserved Chicago population. Study Design  From April 16 to June 16, 2020, a total of 369 patients were screened for COVID-19 at University of Illinois at Chicago with either the Abbott Point-of-Care (POC, n  = 266) or reverse transcription polymerase chain reaction test (RT-PCR, n  = 101). Patient residential data mapped using ESRI ArcGIS Pro was integrated in ESRI's Living Atlas with the Neighborhood Socioeconomic Status Index (NSEI). Results  Precisely, 7.9% (29/369) of screened patients tested positive; 69% (17/29) with the POC test and 31% (12/29) by RT-PCR. The prevalence of an outpatient RT-PCR positive result was 8.9% (9/101). All but one of the 29 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients were either Hispanic or Black, and the majority resided in disadvantaged neighborhoods.