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Osteoarthritis (OA) is a degenerative disease with a high prevalence in the elderly population, but our understanding of its mechanisms remains incomplete. Analysis of serum exosomal small RNA sequencing data from clinical patients and gene expression data from OA patient serum and cartilage obtained from the GEO database revealed a common dysregulated miRNA, miR-199b-5p. In vitro cell experiments demonstrated that miR-199b-5p inhibits chondrocyte vitality and promotes extracellular matrix degradation. Conversely, inhibition of miR-199b-5p under inflammatory conditions exhibited protective effects against damage. Local viral injection of miR-199b-5p into mice induced a decrease in pain threshold and OA-like changes. In an OA model, inhibition of miR-199b-5p alleviated the pathological progression of OA. Furthermore, bioinformatics analysis and experimental validation identified Gcnt2 and Fzd6 as potential target genes of MiR-199b-5p. Thus, these results indicated that MiR-199b-5p/Gcnt2 and Fzd6 axis might be a novel therapeutic target for the treatment of OA.

BackgroundWe aimed to use transcriptomics, bioinformatics analysis, and core gene validation to identify the core gene and potential mechanisms for electroacupuncture (EA) treatment of ulcerative colitis (UC).Materials and methodsEA was performed in mice after induction of UC via dextran sodium sulfate. Body weight, disease activity index (DAI), colon length, and hematoxylin-eosin of the colon tissue were used to evaluate the effects of EA. Mice transcriptome samples were analyzed to identify the core genes, and further verified with human transcriptome database; the ImmuCellAI database was used to analyze the relationship between the core gene and immune infiltrating cells (IICs); and immunofluorescence was used to verify the results.ResultsEA could reduce DAI and histological colitis scores, increase bodyweight and colon length, and improve the expression of local and systemic proinflammatory factors in the serum and colon of UC mice. Eighteen co-differentially expressed genes were identified by joint bioinformatics analyses of mouse and human transcriptional data; Cxcl1 was the core gene. EA affected IICs by inhibiting Cxcl1 expression and regulated the polarization of macrophages by affecting the Th1 cytokine IFN-γ, inhibiting the expression of CXCL1.ConclusionsCXCL1 is the target of EA, which is associated with the underlying immune mechanism related to Th1 cytokine IFN-γ.

Abstract Background Acupuncture at Neiguan (PC6) has long been used for treating cardiovascular diseases, but its antiarrhythmic effect and the underlying mechanisms have not yet been well investigated, especially regarding premature ventricular complexes (PVCs) that occur post-myocardial infarction (MI). The purpose of this study was to study the antiarrhythmic effect of manual acupuncture applied to PC6 for a relatively long period (28 days) and to elucidate the mechanism in mice. Methods An MI mouse model was generated by ligating the left anterior descending coronary artery in male C57/BL6 mice (n = 31). Manual acupuncture at PC6 was applied seven times weekly for 4 weeks. The state of myocardial injury was characterized by electrocardiography (ECG) and echocardiography. Inflammation was detected by ELISA and immunohistochemical stanning. Fibrosis was evaluated by Masson’s trichrome staining. RNA sequencing was used to explore the differentially expressed genes (DEGs) among the different groups after treatment. Results Acupuncture at PC6 lowered the incidence of spontaneous PVCs after MI injury (1/9, 11%) compared to that in mice without acupuncture treatment (6/9, 67%) and improved the ejection fraction from 31.77% in the MI mice to 44.18% in the MI + PC6 mice. Fibrosis was reduced after PC6 treatment. RNA-seq showed many DEGs involved in the immune system and inflammatory response pathway. Further studies confirmed that inflammation at the circulation level and cardiac tissue was inhibited in MI + PC6 mice, accompanied by suppressed sympathetic activation. Conclusions In conclusion, 28-day treatment of acupuncture at PC6 reduced spontaneous PVCs and improved systolic function, possibly by suppressing inflammatory response-mediated fibrosis and sympathetic hyperactivity.

BackgroundChronic pain (CP) patients tend to represent aberrant functional brain activity. Acupuncture is an effective clinical treatment for CP, and some fMRI studies were conducted to discover the alternation of brain regions after acupuncture therapy for CP. However, the heterogeneity of neuroimaging studies has prevented researchers from systematically generalizing the central mechanisms of acupuncture in the treatment of CP.MethodsWe searched bibliographic databases, including PubMed, EMBASE, PsycINFO, Web of Science Core Collection, ScienceDirect, China Academic Journal Network Publishing Database, etc., and trials registration platforms (From inception to September 1st, 2022). Two independent researchers assessed the study's bias and quality. Furthermore, activation likelihood estimation (ALE) analysis was applied to explore aberrant brain functional activity and acupuncture's central mechanism for CP.ResultsTotally 14 studies with 524 CP patients were included in the study. ALE analysis showed that CP patients presented with decreased ALFF/ReHo in the precuneus, posterior cingulate cortex, right inferior parietal lobule, right superior temporal gyrus, cingulate gyrus, superior frontal gyrus, left medial frontal gyrus including medial prefrontal gurus, left middle frontal gyrus.ConclusionThis ALE meta-analysis pointed out that acupuncture could modulate the default mode network, the frontoparietal network to treat CP. This provided a systematic summary of the neuroimage biomarker of acupuncture for the treatment of CP.Systematic review registrationPROSPERO, identifier: CRD42021239633.

Background: The purpose of this study was to investigate the potential involvement of pyruvate kinase M2 (PKM2), an enzyme acting as a rate-limiting enzyme in the final phase of glycolysis, in the regulation of glial activation and brain damage of intracerebral hemorrhage (ICH). Methods: Western blotting and immunofluorescence were performed to investigate PKM2 expression, terminal deoxynucleotidyl transferase deoxyurinary triphosphate (dUTP) nick end labeling staining, hematoxylin and eosin staining, and behavioral tests were employed to evaluate the brain damage of ICH mice, and RNA-seq and bioinformatic analyses were performed to detect gene expression changes in ICH mice treated with TEPP-46. Results: Increased PKM2 levels in perihematomal brain tissue were found starting from 3 days following ICH and peaked at 5 and 7 days post ICH. The increased expression of PKM2 was mainly co-localized with glial fibrillary acidic protein (GFAP)+ astrocytes and ionized calcium binding adaptor molecule-1 (IBA-1)+ microglia. Furthermore, we observed a notable increase in the nuclear translocation of PKM2 in glial cells following ICH. TEPP-46 treatment significantly reduced PKM2 nuclear translocation, and effectively attenuated glial activation and brain injury, and improved functional recovery of mice with ICH. RNA-seq data indicated that 91.1% (205/225) of differentially expressed genes (DEGs) were down-regulated in the TEPP-46 treated groups compared with the vehicle-treated groups in ICH brains. Furthermore, bioinformatic analyses revealed that these down-regulated DEGs were involved in a variety of biological processes, including autophagy and metabolic processes. In addition, the majority of these downregulated DEGs had a primary high expression in neurons, with subsequent expression seen in endothelial cells, microglia, and astrocytes. Conclusions: These results indicate that increased PKM2 nuclear translocation promotes the activation of glial cells after ICH, hence aggravating ICH-induced brain damage, and aggravates the brain injury induced by ICH. This highlights a potential therapeutic target for inhibiting glial activation to attenuate brain injury after ICH.

Background: Acupuncture has been extensively applied to manage irritable bowel syndrome (IBS) in clinical practice in China. Some randomized controlled trials (RCTs) have demonstrated their efficacy, but it has rarely been compared with first-line antispasmodics to verify their effectiveness. Therefore, we compare acupuncture with antispasmodics in the treatment of IBS by using an adjusted indirect treatment comparison meta-analysis.Methods: Embase, OVID Medline, and the Cochrane Central Register of Controlled Trials databases were searched from inception to 14 March 2022, with no language restrictions. RCTs comparing antispasmodics or acupuncture with placebo or one of the antispasmodics were enrolled. The primary outcome of interest was the improvement of abdominal pain. And the secondary outcomes of interest were the relief of global IBS symptoms and adverse events. The random-effects model was utilized to pool data. The effect size was measured by standardized mean difference (SMD) or relative ratio, and the effectiveness of acupuncture and different antispasmodics were ranked by P-scores.Results: Thirty-five RCTs (n = 5,190) were included. The analysis showed that cimetropium, drotaverine, acupuncture, and pinarverium were superior over placebo in relieving abdominal pain; cimetropium (SMD, −3.00 [95%CI, −4.47 to −1.53], P-score = 0.99) ranked the most effective. In pairwise comparisons, acupuncture had a greater improvement than most antispasmodics except cimetropium and drotaverine in relieving abdominal pain, although the between-group difference was statistically insignificant. In the analysis of continuous outcome in the relief of global IBS symptoms, the result showed that pinaverium was more effective (SMD, 1.72 [95%CI, 0.53 to 2.92], P-score = 0.90) than placebo. Trimebutine and acupuncture had greater improvements than placebo, but no significant difference was shown between groups. In pairwise comparisons, acupuncture was more effective than pinaverium (SMD, −1.11 [95%CI, −1.94 to −0.28]) in relieving global IBS symptoms. In the analysis of adverse events, acupuncture had a lower adverse event rate than most of the other antispasmodics.Conclusion: Cimetropium, drotaverine, and acupuncture were all better than placebo in improving abdominal pain. Acupuncture was preferred over pinaverium in relieving global IBS symptoms, and acupuncture had lower adverse events than most antispasmodics.

Background: Probiotic and low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet are two commonly used management approaches for patients with irritable bowel syndrome (IBS). We aimed to evaluate the most effective combinations and components among different probiotics or low FODMAP diet through component network meta-analysis (NMA).Methods: We searched Embase, Ovid Medline, and Web of Science from inception to 21 January 2021. Randomized controlled trials (RCTs) examining the efficacy of probiotics and low FODMAP diet for IBS were included, with placebo, sham diet, or conventional treatments as controls. Binary outcomes were compared among treatments using the relative ratio (RR). A minimally contextualized framework recommended by the GRADE group was used to evaluate the certainty of evidence. The primary efficacy outcome was the relief of global IBS symptoms, and the secondary efficacy outcome was the reduction in IBS symptom scores or abdominal pain scores.Key Results: We included 76 RCTs (n = 8058) after screening 1940 articles. Eight RCTs were classified as low risk of bias. Standard network meta-analysis (NMA) showed that Lactobacillus (RR 1.74, 95% CI 1.22–2.48) and Bifidobacterium (RR 1.76, 95% CI 1.01–3.07) were the most effective for the primary efficacy outcome (high certainty evidence); component NMA showed that Bacillus (RR 5.67, 95% CI 1.88 to 17.08, p = 0.002) and Lactobacillus (RR 1.42, 95% CI 1.07 to 1.91, p = 0.017) were among the most effective components. The results of standard NMA and CNMA analysis of the improvement of overall IBS symptom scores or abdominal pain scores were consistent with this finding.Conclusion:Lactobacillus was the most effective component for the relief of IBS symptoms; Bifidobacterium and Bacillus were possibly effective and need further verification.Systematic Review Registration: website, identifier registration number.

Licorice (Glycyrrhiza glabra) is extensively used owing to the superior pharmacological effects. However, its maximum application potential has not been fully exploited due to the limitation of currently available extraction solvent and methods. In this study, an eco-friendly deep eutectic solvent (NADESs) based ultrasound-assisted extraction (DES-UAE) method was applied to prepare licorice extracts. The DES-UAE using choline chloride and lactic acid as solvent was optimized and modeled by using response surface methodology to maximize the extraction yields of glabridin (GLA) and isoliquiritigenin (ISL). The optimized extracts possessed higher contents of GLA and ISL than available extraction methods, and the enriched products showed superior pharmacological activities in vitro. Furthermore, scanning electron microscopy (SEM) and molecular dynamic simulation analyses were performed to deeply investigate the interaction between solvent and targeted compounds. This study not only provides an eco-friendly method for high-efficient extraction of GLA and ISL from licorice but also illustrates the mechanism of the increased extraction efficacy, which may contribute to the application of licorice and deep insight into extraction mechanism using DES.