Immune escape of SARS-CoV-2 variants to therapeutic monoclonal antibodies: a system review and meta-analysis.

BACKGROUND: Omicron's high transmissibility and variability present new difficulties for COVID-19 vaccination prevention and therapy. In this article, we analyzed the sensitivity of vaccine-induced antibodies as well as the effect of booster vaccinations against Omicron sublineages. METHODS: We looked for Randomized Controlled Trials and cohort studies that reported the COVID-19 vaccines against Omicron sublineages up to 28 July 2022 through PubMed, the Cochrane Library, EMBASE, and Web of Science. Quantitative synthesis was carried out using Stata 16.0 and RevMa5.3, then the serum NT50 and antibody sensitivity to neutralize Omicron sublineages were assessed before and after booster vaccination. This study was registered with PROSPERO number CRD42022350477. RESULTS: This meta-analysis included 2138 patients from 20 studies, and the booster vaccination against Omicron sublineages showed a significant difference compared to 2 dosage: BA.1/BA.1.1 (SMD = 0.80, 95% CI: 0.75-0.85, P = 0.00), BA.2/BA.2.12.1 (SMD = 0.77, 95% CI: 0.69-0.85, P = 0.00), BA.3 (SMD = 0.91, 95% CI: 0.83-1.0, P = 0.00), and BA.4/5 (SMD = 0.77, 95% CI: 0.60-0.94, P = 0.00). The sensitivity of vaccines-induced antibodies decreased by at least 5-folds after booster vaccination, particularly in the case of BA.4/5 which had the most notable decline in vaccine effectiveness. CONCLUSION: After the booster vaccination, the NT50 and the neutralization ability of vaccine-induced antibodies increased, but the susceptibility of antibodies decreased compared with the control virus, which may be a clue for future Omicron sublineages prevention.

ACE2 Is a Prognostic Biomarker and Associated with Immune Infiltration in Kidney Renal Clear Cell Carcinoma: Implication for COVID-19.

BACKGROUND: KIRC is one of the most common cancers with a poor prognosis. ACE2 was involved in tumor angiogenesis and progression in many malignancies. The role of ACE2 in KIRC is still ambiguous. METHODS: Various bioinformatics analysis tools were investigated to evaluate the prognostic value of ACE2 and its association with immune infiltration in KIRC. RESULTS: ACE2 was shown to be downregulated in KIRC at the mRNA and protein level. Low expression of ACE2 protein in KIRC patients was observed in subgroup analyses based on gender, age, weight, tumor grade, and cancer stage. Upregulation of ACE2 in KIRC was associated with a favorable prognosis. ACE2 mRNA expression showed a positive correlation with the abundance of immune cells (B cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells) and the level of immune markers of different immune cells in KIRC. ACE2 expression could affect, in part, the immune infiltration and the advanced cancer stage. Moreover, enrichment analysis revealed that ACE2 in KIRC were mainly involved in translation factor activity, immunoglobulin binding, metabolic pathways, transcriptional misregulation in cancerous cells, cell cycle, and ribosomal activity. Several ACE2-associated kinases, miRNA, and transcription factor targets in KIRC were also identified. CONCLUSION: ACE2 was downregulated in KIRC and served as a prognostic biomarker. It was also shown to be associated with immune infiltration.

Inhibition of Transient Receptor Potential Melastain 7 Enhances Apoptosis Induced by TRAIL in PC-3 cells.

Transient receptor potential melastain 7 (TRPM7) is a bifunctional protein with dual structure of both ion channel and protein kinase, participating in a wide variety of diseases including cancer. Recent researches have reported the mechanism of TRPM7 in human cancers. However, the correlation between TRPM7 and prostate cancer (PCa) has not been well studied. The objective of this study was to investigate the potential the role of TRPM7 in the apoptosis of PC-3 cells, which is the key cell of advanced metastatic PCa. In this study, we demonstrated the influence and potential function of TRPM7 on the PC-3 cells apoptosis induced by TNF-related apoptosis inducing-ligand (TRAIL). The study also found a novel up-regulated expression of TRPM7 in PC-3 cells after treating with TRAIL. Suppression of TRPM7 by TRPM7 non-specific inhibitors (Gd3+ or 2-aminoethoxy diphenylborate (2-APB) ) not only markedly eliminated TRPM7 expression level, but also increased the apoptosis of TRAIL-treated PC-3 cells, which may be regulated by the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway accompany with up-regulated expression of cleaved Caspase-3, (TRAIL-receptor 1, death receptors 4) DR4, and (TRAIL-receptor 2, death receptors 5) DR5. Taken together, our findings strongly suggested that TRPM7 was involved in the apoptosis of PC-3 cells induced by TRAIL, indicating that TRPM7 may be applied as a therapeutic target for PCa.