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.

Alzheimer's disease (AD) is a common and irreversible neurodegenerative disease accompanied by extensive synaptic loss. Previous studies found that moxibustion had good therapeutic effects on AD. We here investigated whether moxibustion could alleviate the cognitive impairment of AD by promoting the "astrocyte-neuron" interaction and enhancing synaptic plasticity. Moxibustion treatment was administrated to Baihui (GV20) and Yongquan (KI1) in APP/PS1 mice. We first evaluated the behavior of APP/PS1 mice with Morris water maze test, and observed the synaptic structure before and after moxibustion intervention. Then, the transcriptome characteristics (TC) and "astrocyte-neuron" interaction were evaluated by spatial transcriptomics (ST). CD38 and its ligand Pecam1, one of the energy shuttle pathways between neurons and astrocytes, were also be detected. The results supported that moxibustion increased learning and memory ability and synaptic structure. ST showed that the TC were more similar between the moxibustion and control groups. Moxibustion enhanced the number of ligand - receptor pairs between astrocytes and neurons. And the score of interaction intensity and the proportion of interaction were also increased. Meanwhile, the energy of astrocytes and neurons was significantly altered. Additionally, moxibustion could significantly improve the function of CD38 and its ligand Pecam1 which were previously reported having the function of transporting mitochondria from astrocytes to neurons, and then providing energy for neurons. Our study provides new evidences for the use of moxibustion to increase the "astrocyte - neuron" interaction thus to enhance synaptic plasticity of APP/PS1 mice.

Objectives. To study the influence of electroacupuncture (EA) and moxibustion on the hippocampus astrocyte and microglia activation in the ulcerative colitis model and to evaluate the mitochondria activity. Methods. 2.5% dextran sodium sulfate‐induced colitis mice were treated by EA or moxibustion. Intestinal pathological structure was observed by hematoxylin and eosin (H&E) staining; the expression of GFAP or S100b (markers for astrocyte), Iba‐1 (a marker for microglia), and Mitofilin (a marker for mitochondria) in hippocampus was detected by immunofluorescence staining or western blot. Results. The results demonstrated that both EA and moxibustion could improve the morphology of distal colonic mucosal epithelia in DSS‐induced colitis mice. Expression of GFAP in the hippocampus was significantly increased after EA or moxibustion treatment. The effects were further supported by WB results. Meanwhile, expression of mitofilin in the hippocampus CA1 and CA3 regions showed the same trend as that of GFAP. Expression of Iba‐1 in the hippocampus showed no significant difference after EA or moxibustion treatment, while the state of microglia changed from resting in control mice to activated state in colitis mice. Conclusion. EA and moxibustion were able to modulate the activation of astrocyte, microglial, and mitochondria in the hippocampus area in the colitis model.

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.

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.