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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To observe the effects of electroacupuncture (EA) on sympathetic nerve-related substance in myocardial tissue in mice with myocardial ischemia (MI), and to explore its possible mechanism., Methods: Thirty adult male C57BL/6 mice were randomly divided into a sham operation group, a model group and an EA group, 10 mice in each one. The model of MI was established in the model group and EA group by ligating the left anterior descending branch of coronary artery. The mice in the sham operation group were not treated with ligating at left anterior descending branch of coronary artery, but the remaining procedure was similar with the model group. The mice in the EA group were treated with EA at "Neiguan" (PC 6) with 2 Hz/100 Hz of frequency and 2 mA of intensity, 20 min per treatment, once a day for totally 5 days. No EA was given for model group and sham operation group. The electrocardiogram was recorded and △ST value was calculated to evaluate the model. TTC staining was applied to evaluate the infarct size. Immunohistochemical (IHC) method was applied to evaluate the positive nerve fiber density in myocardial tissue. Western blot method was applied to test the protein expression levels of neuregulin-1 (NRG-1), tyrosine hydroxylase (TH), growth associated protein-43 (GAP-43)., Results: The electrocardiogram (lead II) results indicated compared with the sham operation group, the S-T segments in the model group and EA group were increased obviously (both P <0.01), indicating the MI model was established successfully. The TTC staining results indicated compared with sham operation group, the infarction size was significantly increased in the model group ( P <0.01); compared with the model group, the infarction size in the EA group was significantly reduced ( P <0.01). The IHC results indicated compared with the sham operation group, the positive nerve fiber density in myocardial was increased in the model group ( P <0.01); compared with the model group, the positive nerve fiber density in myocardial was reduced in the EA group ( P <0.05). The Western blot results indicated compared with the sham operation group, the expression levels of TH, NRG-1 and GAP-43 were significantly increased in the model group ( P <0.01); compared with the model group, the expression level of TH and GAP-43 were significantly reduced ( P <0.01) and that of NRG-1 was increased in the EA group ( P <0.05)., Conclusion: EA could increase the expression of NRG-1 and reduce the expression of TH and GAP-43 in myocardial tissues in MI mice, which could suppress sympathetic nerve hyperexcitability after infarction to achieve myocardial protection effect.

The inflammatory reaction induced by ischemic myocardial injury (IMI) is divided into three phases, i．e. the inflammatory phase, the fibrous proliferative phase and the stable phase. The appropriate inflammatory reaction effectively removes the fragments of myocardial cells, which is the essential phase in the pathological progression of myocardial ischemia (MI). However, the excessive inflammatory reaction may aggravate the myocardial injury. For this reason, the immediate control of the post-injury inflammatory reaction is the principal therapeutic measure and the research hotspot at the present. Acupuncture intervention has been demonstrated to have positive roles in relieving MI and inflammatory reaction by suppressing myocardial inflammatory cytokines (suppressing IL-1β， TNF-α， IL-8, etc.), adjusting inflammatory reaction pathway (NF-κB signaling, TGF-β， etc.)and activating cholinergic anti-inflammatory pathway. Therefore, it is feasible to explore the underlying mechanism of acupuncture therapy in protecting ischemic myocardium based on anti-inflammatory efficacy.

Objective: To observe the effect of electroacupuncture (EA) on insulin signaling pathway in liver tissues of central neuronal specific signal transduction and activator of transcription 5 conditional-knockout ( Stat 5 NKO) mice, so as to explore its mechanism underlying improvement of insulin resistance (IR)．., Methods: Twenty-four male Stat 5 NKO mice were randomly divided into model and EA groups ( n ＝12 mice/group), and 12 Stat 5 fl/fl mice were used as the normal control group. EA (2 Hz/15 Hz, 0.8－1.0 mA) was alternatively applied to ipsilateral "Zusanli" (ST 36) and "Neiting" (ST 44) for 20 min, once a day, 6 times a week for 4 weeks. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed, and the values of fasting plasma glucose (FPG) and fasting insulin (FINS) were measured by glucometer and ELISA, separately. The insulin sensitivity index (ISI) was calculated. The phosphorylation protein expressions of insulin receptor substrate 1 (IRS 1), insulin receptor β (IRβ) and protein kinases B (Akt) in the liver tissues were detected by Western blot., Results: In Stat 5 NKO mice (model group), FPG level and glucose area under the curve (GAUC) of ITT and GTT were significantly increased ( P <0.01, P <0.05, P <0.001), while the ISI was notably down-regulated in comparison with the Stat 5 fl/fl mice (normal group, P <0.01), suggesting an impairment of both glucose tolerance (GT) and insulin tolerance (IT) in mice of the model group. After the EA treatment, the increased FPG and GAUC levels and the decreased ISI were reversed markedly ( P <0.05, P <0.01, P <0.001). No significant differences were found in FINS among the three groups ( P >0.05). Compared with the normal group, the protein expression levels of liver p-IRS 1 and p-IRβ were significantly up-regulated ( P <0.001), and the p-Akt expression was significantly down-regulated ( P <0.01) in the model group. Following EA treatment, the increased p-IRS 1 and p-IRβ protein expression and the decreased p-Akt expression were apparently reversed in the EA group relevant to the model group ( P <0.001, P <0.01)．., Conclusion: EA can improve the IR induced by central neuronal Stat 5-knockout in mice, which may contribute to its effectiveness in regulating hepatic IRβ/IRS 1/Akt signaling pathway.