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Glioblastoma multiforme (GBM) is the most frequent primary brain malignancy in adults. Despite improvements in imaging and therapy, the prognosis remains poor. To evaluate and compare the impact of combining bevacizumab with temozolomide and radiotherapy on progression-free survival (PFS) and overall survival (OS) in patients diagnosed with GBM. A comprehensive search was conducted across multiple databases, including PubMed, Embase, Scopus, and The Cochrane Library, covering the period from their inception to December 2022. The collected data underwent analysis employing appropriate statistical methods. Six articles were included in this systematic review and meta-analysis. The addition of bevacizumab to the combination of temozolomide/radiotherapy did not increase the OS in GBM patients. The pooled odds ratio (OR) was 0.843 (95% CI: 0.615-1.156, P = 0.290). The addition of bevacizumab to radiotherapy/temozolomide did not increase the PFS in patients with GBM. The pooled OR was 0.829 (95% CI: 0.561-1.224, P = 0.346). The funnel plot demonstrated the absence of the alleged pleiotropic effects by showing no evidence of observable variability across the estimations. This study does not support the benefit of the addition of bevacizumab to temozolomide and radiotherapy in improving OS and PFS in GBM patients., (Copyright © 2024 Copyright: © 2024 Neurology India, Neurological Society of India.)

SARS-CoV-2 belongs to the subgenus Sarbecovirus , which universally encodes the accessory protein ORF6. SARS-CoV-2 ORF6 is an antagonist of the interferon (IFN)-mediated antiviral response and plays an important role in viral infections. However, the mechanism by which the host counteracts the function of ORF6 to restrict viral replication remains unclear. In this study, we found that most ORF6 proteins encoded by sarbecoviruses could be ubiquitinated and subsequently degraded via the proteasome pathway. Through extensive screening, we identified that the deubiquitinase USP1, which effectively and broadly deubiquitinates sarbecovirus ORF6 proteins, stabilizes ORF6 proteins, resulting in enhanced viral replication. Therefore, ubiquitination and deubiquitination of ORF6 are important for antagonizing IFN-mediated antiviral signaling and influencing the virulence of SARS-CoV-2. These findings highlight an essential molecular mechanism and may provide a novel target for therapeutic interventions against viral infections.IMPORTANCEThe ORF6 proteins encoded by sarbecoviruses are essential for effective viral replication and infection and are important targets for developing effective intervention strategies. In this study, we confirmed that sarbecovirus ORF6 proteins are important antagonists of the host immune response and identified the regulatory mechanisms of ubiquitination and deubiquitination of most sarbecovirus ORF6 proteins. Moreover, we revealed that DUB USP1 prevents the proteasomal degradation of all ORF6 proteins, thereby promoting the virulence of SARS-CoV-2. Thus, impeding ORF6 function is helpful for attenuating the virulence of sarbecoviruses. Therefore, our findings provide a deeper understanding of the molecular mechanisms underlying sarbecovirus infections and offer potential new therapeutic targets for the prevention and treatment of these infections., Competing Interests: The authors declare no conflict of interest.

The present study aims to identify immune-related prognostic genes in colorectal cancer (CRC), and to explore potential mechanisms through which these genes regulate CRC progression. We first constructed a prognostic risk model based on seven gene signatures [cluster of differentiation-36 ( CD36 ), chemokine (C-X-C-motif) ligand 13 ( CXCL13 ), fibroblast growth factor receptor 4 ( FGFR4 ), gamma-amino-butyric acid type B receptor 1 ( GABBR1 ), lysosome-associated membrane glycoprotein 3 ( LAMP3 ), recombinant matrix metalloproteinase 12 ( MMP12 ), and protein phosphatase 1H ( PPM1H )] using integrated bioinformatic analyses. FGFR4, GABBR1 , and LAMP3 were highly expressed in CRC cell lines (in comparison with a normal colonic epithelial cell line), while CD36, CXCL13, MMP12 , and PPM1H were weakly expressed. These in vitro expression results were largely consistent with our bioinformatic analysis. A prognostic model was generated to identify a high-risk group with worse survival outcome based on Kaplan-Meier analysis. Our prognostic model showed superior accuracy in both the training and test cohorts. In addition, we found that the low-risk subgroup exhibited greater infiltration by M1 macrophages, CD8 + T cells, CD4 + T cells, and activated NK cells. In conclusion, our findings provide evidence that seven immune-related hub genes can be considered as gene signatures to predict CRC prognosis and to differentiate CRC patient benefit, ultimately serving as a guide for individualized immunotherapy., Competing Interests: None., (AJTR Copyright © 2024.)

Objective To investigate the molecular mechanism of palmitic acid (PA) inducing inflammation and epithelial to mesenchymal transdifferentiation (EMT) in human renal tubular epithelial cells (RTECs). Methods The cell lipid accumulation model was prepared by RTECs and the cells were divided into blank control group, bovine serum albumin (BSA) group, PA group, and PA combined with stimulator of interferon genes (STING) specific inhibitor H151 group. The lipid accumulation of RTECs were detected by oil red O staining. Real-time quantitative PCR was used to detect the mRNA levels of interleukin 6 (IL-6), IL-8, transforming growth factor β1 (TGF-β1), and type 1 collagen alpha 1 chain (COL1A1) in RTECs. The protein expressions of STING, nuclear factor-κB p65 (NF-κB p65), phosphorylated NF-κB p65 (p-NF-κB p65), TGF-β1, and type 1 collagen (Col1) were detected by Western blot and the expression and distribution of Col1 in RETCs were detected by immunofluorescence chemical staining. Results Compared with the control group, PA stimulated the lipid deposition, the expression of STING, and the phosphorylation of NF-κB p65 obviously, up-regulated the mRNA levels of IL-6, IL-8, TGF-β1, and COL1A1 significantly, increased the protein expressions of TGF-β1 and Col1 and the distribution of Col1 in RTECs; compared with those in the PA group, after H151 treatment, the expression of STING and the phosphorylation of NF-κB p65 decreased notably, the mRNA levels of IL-6, IL-8, TGF-β1, and COL1A1 were down-regulated dramatically, and the protein expressions of TGF-β1 and Col1 declined with reduced distribution of Col1. Conclusion PA induces lipid deposition, activated the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/STING pathway, and caused inflammation and EMT in RTECs.