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We 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). EA was performed in mice after induction of UC 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. EA 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; was the core gene. EA affected IICs by inhibiting expression and regulated the polarization of macrophages by affecting the Th1 cytokine IFN-γ, inhibiting the expression of CXCL1. CXCL1 is the target of EA, which is associated with the underlying immune mechanism related to Th1 cytokine IFN-γ.

As potentially important biosensors within the intestinal mucosal barrier, gut sensory neurons appear to dynamically orchestrate tissue homeostasis through multimodal integration of mechanical forces, chemical cues, and microbial metabolites. While current research indicates gut sensory neurons may play a significant role in the pathophysiology of IBD/IBS, the precise etiological mechanisms underlying these disorders require further investigation. In the enteric nervous system, intrinsic primary afferent neurons (IPANs) show distinct molecular characteristics compared to peripheral sensory neurons originating from the dorsal root ganglia (DRG) and vagal ganglia (NG/JG, nodose/jugular ganglia). These neuronal subtypes appear to orchestrate bidirectional epithelial-immune communication through context-dependent release of neurochemical signals, potentially establishing a dynamic neuromodulatory network. This comprehensive review will examine the latest findings on the relationship between these sensory neurons and intestinal diseases, and explore an integrated therapeutic framework based on a triple synergistic strategy. This framework could encompass precise molecular-level modulation through targeting neurotransmitters and their receptors, systemic-level neural regulation utilizing electrical nerve stimulation techniques, and ecological reprogramming mediated by gut microbiota. This potential approach may provide a possible translational pathway from mechanistic exploration to practical application, with implications for personalized clinical interventions for IBD/IBS.

Accumulating evidence shows that the abnormal increase in the mortality of intestinal epithelial cells (IECs) caused by apoptosis, pyroptosis, and necroptosis is closely related to the function of mucous membrane immunity and barrier function in patients with ulcerative colitis (UC). As a procedural death path that integrates the above-mentioned many deaths, the role of PANoptosis in UC has not been clarified. This study aims to explore the characterization of PANoptosis patterns and determine the potential biomarkers and therapeutic targets. We constructed a PANoptosis gene set and revealed significant activation of PANoptosis in UC patients based on multiple transcriptome profiles of intestinal mucosal biopsies from the GEO database. Comprehensive bioinformatics analysis revealed five key genes (ZBP1, AIM2, CASP1/8, IRF1) of PANoptosome with good diagnostic value and were highly correlated with an increase in pro-inflammatory immune cells and factors. In addition, we established a reliable ceRNA regulatory network of PANoptosis and predicted three potential small-molecule drugs sharing calcium channel blockers that were identified, among which flunarizine exhibited the highest correlation with a high binding affinity to the targets. Finally, we used the DSS-induced colitis model to validate our findings. This study identifies key genes of PANoptosis associated with UC development and hypothesizes that IRF1 as a TF promotes PANoptosome multicomponent expression, activates PANoptosis, and then induces IECs excessive death.

Aims This study aimed to investigate the relationship between ulcerative colitis (UC) and anxiety and explore its central mechanisms using colitis mice. Methods Anxiety‐like behavior was assessed in mice induced by 3% dextran sodium sulfate (DSS) using the elevated plus maze and open‐field test. The spatial transcriptome of the hippocampus was analyzed to assess the distribution of excitatory and inhibitory synapses, and Toll‐like receptor 4 (TLR4) inhibitor TAK‐242 (10 mg/kg) and AAV virus interference were used to examine the role of peripheral inflammation and central molecules such as Glutamate Receptor Metabotropic 1 (GRM1) in mediating anxiety behavior in colitis mice. Results DSS‐induced colitis increased anxiety‐like behaviors, which was reduced by TAK‐242. Spatial transcriptome analysis of the hippocampus showed an excitatory‐inhibitory imbalance mediated by glutamatergic synapses, and GRM1 in hippocampus was identified as a critical mediator of anxiety behavior in colitis mice via differential gene screening and AAV virus interference. Conclusion Our work suggests that the hippocampus plays an important role in brain anxiety caused by peripheral inflammation, and over‐excitation of hippocampal glutamate synapses by GRM1 activation induces anxiety‐like behavior in colitis mice. These findings provide new insights into the central mechanisms underlying anxiety in UC and may contribute to the development of novel therapeutic strategies for UC‐associated anxiety. Anxious behavior in mice with colitis was associated with an imbalance in hippocampal excitatory inhibition due to the overactivation of glutamate synapses. Peripheral suppression of colon inflammation or downregulation of GRM1 expression by AAV virus interference can significantly improve anxiety‐like behavior.

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.

The role of endoplasmic reticulum stress (ERS) in the immune-inflammatory dysregulation and intestinal fibrosis associated with ulcerative colitis (UC) remains unclear. This study aims to identify ERS-related genes involved in UC fibrosis and explore potential therapeutic targets. Differentially expressed ERS-related genes (DE-ERGs) were identified through comprehensive analysis of public datasets. Machine learning methods screened VWF, MZB1, COL1A1, and LOXL2 as key regulators. Immune infiltration analysis, protein-protein interaction (PPI) network analysis, and gene set variation analysis (GSVA) were performed to clarify their roles in UC fibrosis. Drug prediction was conducted using the Connectivity Map (CMap) database, supplemented by a literature review. The predicted drugs were ranked based on their binding affinities as follows: IKK-16 > Quercetin > Curcumin > Resveratrol > Budesonide > Trimebutine > Colchicine > Betamethasone > Pioglitazone > Metformin. IKK-16 showed the highest binding affinity for treating UC fibrosis. COL1A1, LOXL2, and VWF were identified as key drivers of UC intestinal fibrosis, supported by immune infiltration and PPI network analyses. These results suggest that ERS-related genes, particularly COL1A1, LOXL2, and VWF, may regulate UC fibrosis through interactions with immune cells. IKK-16 shows promise as a therapeutic agent. These findings provide new insights into UC pathogenesis and potential clinical treatment strategies.

To analyze the role of disulfidptosis in ulcerative colitis (UC), large-scale datasets combined with weighted gene co-expression network analysis (WGCNA) and machine learning were utilized and analyzed. When the hub genes that are associated with UC disease phenotypes and have predictive performance were identified, immune cell infiltration and the CeRNA network were constructed, the role of hub genes in UC pathogenies and biotherapy were investigated, and molecular docking studies and mice-verified tests were carried out to further explore the potential core genes and potential target. Finally, we found 21 DRGs involved in UC pathogenesis, including SLC3A2, FLNA, CAPZB, TLN1, RPN1, etc. Moreover, SLC3A2, TLN1, and RPN1 show a notable correlation with UC inflammatory state, and the expression of DRGs is closely related to the response to UC biotherapy. Our study suggests that disulfidptosis plays a crucial role in the pathogenesis and disease progression of UC. Higher expression of DRGs is commonly observed in moderate to severe UC patients, which may also affect their response to biologic therapies. Among the identified genes, SLC3A2 stands out, providing new insights into the underlying mechanisms of UC and potentially serving as a novel therapeutic target for the treatment of UC.

Background Increasing evidence have indicated the relationship between intestinal dysbiosis and hypertension. We aimed to evaluate the effect of the electroacupuncture (EA) on intestinal microbiota in patients with stage 1 hypertension. Methods 93 hypertensive patients and 15 healthy subjects were enrolled in this study. Applying a highly accurate oscillometric device to evaluate the antihypertensive effect of EA. 16S rRNA sequencing was used to profile stool microbial communities from Healthy group, Before treatment (BT) group and After treatment (AT) group, and various multivariate analysis approaches were used to assess diversity, composition and abundance of intestinal microbiota. Results In this study, EA significantly decreased the blood pressure (BP) of hypertensive patients. Higher abundance of Firmicutes and lower Bacteroidetes abundance were observed in the BT group compared to the Healthy group. And EA treatment significantly decreased the Firmicutes/Bacteroidetes ratio compared to the BT group. Moreover, at the genus level, there was an increased abundance of Escherichia-Shigella in patients with hypertension, while Blautia were decreased, and EA reversed these changes. Conclusions Our study indicates that EA can effectively lower BP and improve the structure of intestinal microbiota which are correlate with the alteration of blood pressure by electroacupuncture. Trial registration: Clinicaltrial.gov, NCT01701726. Registered 5 October 2012, https://clinicaltrials.gov/ct2/show/study/NCT01701726

ObjectiveThe Shixiangru (Mosla chinensis Maxim) total flavonoids (STF) mainly contain luteolin and apigenin. The study aims to examine the inhibitory effects of STF on anti-H1N1 influenza virus and its related molecular mechanisms in pneumonia mice.MethodsThe viral pneumonia mice were treated with Ribavirin or various doses of STF. We observed histological changes of lung by immunohistochemistry and measured lung index to value anti-influenza virus effects of STF. The concentrations of inflammatory cytokines and anti-oxidant factors were detected by ELISA. RT-PCR and western blot assays were used to determine the expression level of TLR pathway’s key genes and proteins in lung tissues.ResultsWe found that the pathological changes of lung in the viral pneumonia mice obviously alleviated by STF treatments and the STF (288 or 576 mg/kg) could significantly decrease lung indices. Moreover, the up-regulation (IL-6, TNF-α, IFN-γ, and NO) and down-regulation (IL-2, SOD and GSH) of inflammatory cytokines and anti-oxidant factors were associated with higher clearance of virus and reduction of inflammatory lung tissue damage. Meanwhile, the expression levels of TLR3, TLR7, MyD88, TRAF3 and NF-κB p65 of the TLR pathway were reduced by STF treatment.ConclusionsThis study suggested that STF may be a promising candidate for treating H1N1 influenza and subsequent viral pneumonia.

Objectives. To study whether moxibustion can improve the learning and memory ability of APP/PS1 mice by reducing the pathological products Aβ and Tau protein via decreasing N6-methyladenosine (m6A). Methods. APP/PS1 mice were randomly divided into model group (APP/PS1) and moxibustion group (APP/PS1+Mox). C57BL/6J mice were used as a control group (Control). Learning and memory abilities were assessed by the Morris water maze. Aβ, Tau, phosphorylated Tau (p-Tau), and YTHDF1 proteins were detected in the mouse cortex and hippocampus by immunofluorescence and western blot. Altered m6A expression levels in hippocampal and cortical tissues were measured with the m6A RNA methylation quantification assay kit. RNA transcript levels of YTHDF1, METTL3, and FTO in the hippocampus and cortex were measured by q-PCR. Results. Moxibustion shortened the escape latency, increased the number of platform crossings, and increased the percentage of swimming time in the target quadrant of APP/PS1 mice. Meanwhile, moxibustion reduced the levels of Aβ, Tau, and p-Tau proteins both in the hippocampal and cortical regions of APP/PS1 mice. In addition, the total amount of m6A in the hippocampal and cortical regions of APP/PS1 mice was significantly reduced after moxibustion. The expression of YTHDF1 in the hippocampal region of APP/PS1 mice increased and that in the cortical region decreased after moxibustion treatment. Conclusion. Moxibustion improves the learning and memory abilities and reduces the deposition of Aβ and Tau protein pathological products in APP/PS1 mice. This may be related to the fact that moxibustion reduces the total amount of m6A and inhibits its binding enzyme YTHDF1 in the hippocampus and cortex of APP/PS1 mice.