MiRNA is a class of small non-coding RNA which has an important effect on posttranscriptional gene regulation. It can regulate the expression of the target gene at the mRNA level and further influence the protein level of the target gene. We found that ULK1 may be the target gene of miR-26a-5p, and ULK1 (unc-51 like autophagy activating kinase 1) is a key component in autophagy pathway. In this study, we overexpressed miR-26a-5p by transfecting miR-26a-5p mimic into cells and simultaneously inhibited miR-26a-5p by transfecting miR-26a-5p inhibitor into cells. We demonstrated that overexpression of miR-26a-5p can reduce the expression of ULK1 and collagen I, and decrease the activation of LC3-I to LC3-II. In contrast, inhibition of miR-26a-5p can increase the expression of ULK1 and collagen I, and increase the activation of LC3-I to LC3-II. The Dual-luciferase reporter assay showed that miR-26a-5p directly acted on the 3′UTR of ULK1 and thus affected the expression of ULK1. As such, our study demonstrated that miR-26a-5p might regulate the autophagy in cardiac fibroblasts by targeting ULK1, which may have an effect on cardiac fibrosis. To our knowledge, this is the first study that shows miR-26a-5p regulates the autophagic pathway in cardiac fibroblasts.

Background: The application of cerebellar transcranial magnetic stimulation (TMS) in stroke patients has received increasing attention due to its neuromodulation mechanisms. However, studies on the effect and safety of cerebellar TMS to improve balance capacity and activity of daily living (ADL) for stroke patients are limited. This systematic review and meta-analysis aimed to investigate the effect and safety of cerebellar TMS on balance capacity and ADL in stroke patients. Method: A systematic search of seven electronic databases (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang and Chinese Scientific Journal) were conducted from their inception to October 20, 2023. The randomized controlled trials (RCTs) of cerebellar TMS on balance capacity and/or ADL in stroke patients were enrolled. The quality of included studies were assessed by Physiotherapy Evidence Database (PEDro) scale. Results: A total of 13 studies involving 542 participants were eligible. The pooled results from 8 studies with 357 participants showed that cerebellar TMS could significantly improve the post-intervention Berg balance scale (BBS) score (MD = 4.24, 95%CI = 2.19 to 6.29, P < 0.00001; heterogeneity, I² = 74%, P = 0.0003). The pooled results from 4 studies with 173 participants showed that cerebellar TMS could significantly improve the post-intervention Time Up and Go (TUG) (MD=-1.51, 95%CI=-2.8 to -0.22, P = 0.02; heterogeneity, I² = 0%, P = 0.41). The pooled results from 6 studies with 280 participants showed that cerebellar TMS could significantly improve the post-intervention ADL (MD = 7.75, 95%CI = 4.33 to 11.17, P < 0.00001; heterogeneity, I² = 56%, P = 0.04). The subgroup analysis showed that cerebellar TMS could improve BBS post-intervention and ADL post-intervention for both subacute and chronic stage stroke patients. Cerebellar high frequency TMS could improve BBS post-intervention and ADL post-intervention. Cerebellar TMS could still improve BBS post-intervention and ADL post-intervention despite of different cerebellar TMS sessions (less and more than 10 TMS sessions), different total cerebellar TMS pulse per week (less and more than 4500 pulse/week), and different cerebellar TMS modes (repetitive TMS and Theta Burst Stimulation). None of the studies reported severe adverse events except mild side effects in three studies. Conclusions: Cerebellar TMS is an effective and safe technique for improving balance capacity and ADL in stroke patients. Further larger-sample, higher-quality, and longer follow-up RCTs are needed to explore the more reliable evidence of cerebellar TMS in the balance capacity and ADL, and clarify potential mechanisms.

Alcohol has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC). Studies have demonstrated that alcohol intake increases the risk of breast cancer, and alcohol also stimulates breast cancer cell growth. Deregulation of Pol III genes is tightly associated with tumour development. Transcription factor II-B (TFIIB)-related factor 1 (Brf1) is a transcription factor that specifically regulates Pol III gene transcription. Our in vivo and in vitro studies have indicated that alcohol enhances the transcription of Pol III genes to cause an alteration of cellular phenotypes, which is closely related with human breast cancer. Betaine is a vegetable alkaloid and has antitumor functions. Most reports about betaine show that the consumption level of betaine is inversely associated with a risk of breast cancer. Although different mechanisms of betaine against tumour have been investigated, nothing has been reported on the effect of betaine on the deregulation of Brf1 and Pol III genes. In this study, we determine the role of betaine in breast cancer cell growth and colony formation and explore its mechanism. Our results indicate that alcohol increases the rates of growth and colony formation of breast cancer cells, whereas betaine is able to significantly inhibit the effects of alcohol on these cell phenotypes. Betaine decreases the induction of Brf1 expression and Pol III gene transcription caused by ethanol to reduce the rates of cell growth and colony formation. Together, these studies provide novel insights into the role of betaine in alcohol-caused breast cancer cell growth and deregulation of Brf1 and Pol III genes. These results suggest that betaine consumption is able to prevent alcohol-associated human cancer development.

Background: Dual-site transcranial magnetic stimulation (TMS) has emerged as a promising neuromodulation technique in stroke rehabilitation. By targeting multiple brain regions, dual-site TMS may enhance neuroplasticity more effectively than single-site stimulation. However, its clinical efficacy remains uncertain.Objective: To systematically evaluate the effects of dual-site TMS in improving motor function and activities of daily living (ADL) in patients with stroke.Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) following PRISMA guidelines. Seven electronic databases were searched from inception to February 19, 2024. Studies comparing dual-site TMS with single-site TMS, sham dual-site TMS, or routine rehabilitation in stroke patients were included. Outcomes included Fugl-Meyer Assessment (FMA), FMA-Upper Limb (FMA-UL), Action Research Arm Test (ARAT), Barthel Index (BI), Modified Barthel Index (MBI), Wolf Motor Function Test (WMFT), and others. Methodological quality was assessed using the PEDro scale. Meta-analyses were performed using a random-effects model.Results: Fourteen RCTs involving 724 participants were included. Dual-site TMS significantly improved upper limb motor function compared with single-site TMS (MD = 7.07, 95% CI: 1.46 to 12.68, p < 0.001) and sham dual-site TMS (MD = 14.45, 95% CI: 6.23 to 22.66, p < 0.001). ADL outcomes also favored dual-site TMS over single-site TMS (MD = 9.90, 95% CI: 7.82 to 11.98, p < 0.001) and sham dual-site TMS (MD = 21.13, 95% CI: 9.37 to 32.88, p < 0.001). Subgroup analyses suggested enhanced benefits in subacute phase stroke and in protocols with >20 sessions. Sensitivity analysis confirmed robustness of findings. No serious adverse events were reported.Conclusion: Dual-site TMS combined with routine rehabilitation is more effective than single-site TMS or sham dual-site TMS in improving motor function and ADL among stroke patients. These findings support its clinical application as an adjunct to conventional therapy. Further high-quality trials are needed to optimize stimulation protocols and confirm long-term effects.