Regulatory T and CXCR3+ Circulating Tfh Cells Concordantly Shape the Neutralizing Antibody Responses in Individuals Who Have Recovered from Mild COVID-19.

Regulatory T (Treg) cells are involved in the antiviral immune response in patients with coronavirus disease 2019 (COVID-19); however, whether Treg cells are involved in the neutralizing antibody (nAb) response remains unclear. Here, we found that individuals who recovered from mild but not severe COVID-19 had significantly greater frequencies of Treg cells and lower frequencies of CXCR3+ circulating T follicular helper (cTfh) cells than healthy controls. Furthermore, the frequencies of Treg and CXCR3+ cTfh cells were negatively and positively correlated with the nAb responses, respectively, and Treg cells was inversely associated with CXCR3+ cTfh cells in individuals who recovered from mild COVID-19 but not in those with severe disease. Mechanistically, Treg cells inhibited memory B-cell differentiation and antibody production by limiting the activation and proliferation of cTfh cells, especially CXCR3+ cTfh cells, and functional molecule expression. This study provides novel insight showing that mild COVID-19 elicits concerted nAb responses, which are shaped by both Treg and Tfh cells.

ELAVL1 regulates glycolysis in nasopharyngeal carcinoma cells through the HMGB3/ß-catenin axis.

BACKGROUND: The role of ELAVL1 in the progression of various tumors has been demonstrated. Our research aims to investigate how ELAVL1 controls the glycolytic process in nasopharyngeal carcinoma cells through the HMGB3/ß-catenin pathway. METHODS: The expression of ELAVL1 was detected in clinical tumor samples and nasopharyngeal carcinoma cell lines. A subcutaneous tumor model was established in nude mice to investigate the role of ELAVL1 in tumor progression. The relationship between HMGB3 and ELAVL1 was validated by RNA pull down and RIP assays. TOPFlash/FOPFlash reporter assay was used to detect ß-catenin activity. Assay kits were utilized to measure glucose consumption, lactate production, and G6PD activity in nasopharyngeal carcinoma cells. Western blot was conducted to detect the expression of glycolysis-related proteins. The glycolytic capacity was analyzed through extracellular acidification rate (ECAR). RESULTS: In both clinical samples and nasopharyngeal carcinoma cell lines, the expression levels of ELAVL1 mRNA and protein were found to be upregulated. Knockdown of ELAVL1 significantly inhibited the in vivo proliferation of nasopharyngeal carcinoma and suppressed the glycolytic capacity of nasopharyngeal carcinoma cells. ELAVL1 interacts with HMGB3, leading to an increase in the stability of HMGB3 mRNA. Overexpression of HMGB3 elevated the reduced ß-catenin activity caused by sh-ELAVL1 and reversed the inhibitory effect of sh-ELAVL1 on cellular glycolytic capacity. Treatment with ß-catenin inhibitor (FH535) effectively suppressed the promotion of glycolytic capacity induced by HMGB3 overexpression. CONCLUSIONS: ELAVL1 promotes glycolysis in nasopharyngeal carcinoma cells by interacting with HMGB3 to stabilize HMGB3 mRNA, thereby activating ß-catenin pathway. Therefore, targeting the ELAVL1-HMGB3-ß-catenin axis has the potential to be a novel approach for treating nasopharyngeal carcinoma.

Effectiveness of Home-Based Exercise for Nonspecific Shoulder Pain: A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the effectiveness of home-based exercise to treat nonspecific shoulder pain (NSSP). DATA SOURCES: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health, Cochrane Controlled Register of Trials, and Physiotherapy Evidence Database were searched from inception to January 2022. STUDY SELECTION: Independent reviewers selected randomized controlled trials that compared the effects of home-based exercise alone with no treatment or other conservative treatments in individuals with nonsurgical painful shoulder disorders. The primary outcomes were shoulder pain intensity and function, and the secondary outcome was shoulder range of motion (ROM). DATA EXTRACTION: Two reviewers independently conducted data extraction. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool, and the overall quality of the evidence was evaluated using the Grading of Recommendation Assessment, Development, and Evaluation approach. DATA SYNTHESIS: Twelve studies were included in the review, and 10 studies were included in the meta-analysis. Low to moderate quality of evidence indicated that home-based exercise alone and other conservative treatments showed equal improvements in pain intensity reduction (mean difference [MD], 0.27; 95% confidence interval [CI], -0.12 to 0.65; I2=30%), function (standardized mean difference [SMD], 0.12; 95% CI, -0.14 to 0.38; I2=16%), flexion ROM (MD, 4.61; 95% CI, -1.16 to 10.38; I2=54%), and abduction ROM (MD, 3.74; 95% CI, -12.44 to 19.93; I2=82%). Very low quality of evidence indicated that home-based exercise alone was more effective than no treatment for pain intensity reduction (MD, -1.47; 95% CI, -2.33 to -0.61) and function improvement (SMD, -0.81; 95% CI, -1.31 to -0.31; large effect). CONCLUSIONS: Home-based exercise alone may be equally effective as other conservative treatments and superior to no treatment for the treatment of NSSP. To draw firmer conclusions, further research is required to validate these findings.