Ulcerative colitis (UC) is a chronic inflammatory bowel disease in which macrophages are key regulators of immune activation, tissue injury, and repair. However, whether macrophage heterogeneity in UC is better understood as discrete subpopulations or as a continuum of functional states remains unclear. Here, we applied an interpretable probabilistic annotation framework, MacGuide-UC, to assist macrophage identification in single-cell transcriptomic data and to support downstream analysis of macrophage state organization in UC. Integrating functional program modeling, trajectory inference, cell–cell communication analysis, bulk transcriptomic validation, and perturbation-informed analysis, we systematically characterized macrophage functional remodeling in UC. Our results suggest that macrophages in UC are organized as a continuum of functional states rather than sharply separated clusters. This continuum was associated with antigen presentation, inflammatory regulation, iron-stress responses, tissue remodeling, and microenvironmental communication. Pseudotime analysis supported gradual state transitions, whereas bulk validation confirmed the disease relevance of macrophage-associated feature genes. Perturbation-informed analysis further nominated candidate regulators, including LGALS3, associated with macrophage state remodeling. Together, these findings support a continuum-based view of macrophage organization in UC.

To comprehensively investigate driven ribotoxic stress response (RSR) activation of M1 macrophage polarization in ulcerative colitis (UC), Gene Set Variation Analysis (GSVA) of intestinal tissues, weighted gene co-expression network analysis (WGCNA) based identification of RSR hub genes correlated with immune infiltration, and single-cell RNA sequencing were used. The multi-modal approach identified six core RSR hub genes (SNAL1, MDM2, MAPK11, MAP3K20, E2F1, BMP6) and established MAP3K20 as the pivotal kinase coordinating RSR-mediated M1 macrophage polarization in UC pathogenesis. Using DSS-induced UC models, we collectively demonstrated that MAP3K20 concurrent regulation of JNK/p38 signaling drive M1 macrophage polarization and UC inflammation, while pharmacological inhibition with Vemurafenib (MAP3K20 inhibitor) effectively attenuated both pathway activation and pathological damage. Our study provides a potential novel therapeutic target and clue for treating UC.

IntroductionUlcerative colitis (UC) is a chronic inflammatory disease. Patients with UC typically exhibit disruption of the Treg/Th17 immune axis, but its exact mechanism is still unclear.MethodsThis study first analyzed RNA- seq data from public databases of humans and mice, and in vitro cytology experiments were conducted to induce or inhibit the expression of SIRT1. In vivo, UC mice were treated with moxibustion and SIRT1 inhibitor EX-527 to confirm the changes in the transcription factors identified through analysis of the datasets.ResultsThe results show that Treg/Th17 axis disruption is an important feature of UC. Differential gene expression and immune infiltration analysis showed that upstream transcription factors, including Forkhead box P3 (FOXP3), were significantly disrupted. In vitro cytology experiments, the results indicate that SIRT1 is activated in LPS induced inflammation, subsequently perturbing the Treg/Th17 immune balance axis. Finally, in vivo studies, the results have shown that administering EX-527 to inhibit SIRT1 leads to an increasing in FOXP3 expression and a decreasing in RORγt expression in UC colon tissue. In addition, the results indicate that traditional Chinese moxibustion can down regulate the expression of SIRT1, directly affecting the balance of Th17/Treg axis, and the combined use of EX-527 further improves the therapeutic effect of moxibustion.ConclusionOur research shows that inhibition SIRT1 can regulate Treg and Th17 immune balance axis. This finding indicates a new important potential target for the treatment of UC.

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.

IntroductionThe 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.MethodsDifferentially 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.ResultsThe 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.DiscussionThese 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.

Ulcerative colitis (UC) and Alzheimer's disease (AD) share a common etiology as inflammatory diseases characterized by barrier deterioration. The aim of this study is to elucidate how neutrophil extracellular traps (NETs), serving as a comorbid etiological factor, can trigger the dysfunction in both the intestinal barrier and blood-brain barrier (BBB). Integrated bioinformatics analysis revealed 14 overlapped NETs-related differential expressed genes in UC and AD, which strongly featured barrier dysfunction. The following verification experiments identified enriched NETs, as well as damaged intestinal epithelium and BBB permeability, in the colon and prefrontal cortex of colitis mice and APP/PS1 mice. By employing pharmacological interventions (Cl-amidine and Disulfiram), we disrupted the formation of NETs and discovered significantly restored barrier integrity and attenuated inflammation. Further enrichment and correlation analysis indicated, for the first time, DDIT4/IL-1 beta NETs might drive macrophage-mediated phagocytosis to induce barrier dysfunction in UC and AD. Our findings originally established the peripheral-central inflammation interactions of UC and AD from the perspective of NETs, highlighting the potential valuable roles in gut-brain interactions and future clinic translational therapeutics.

BackgroundDefective efferocytosis in ulcerative colitis (UC) exacerbates inflammation due to impaired clearance of apoptotic cells, yet the molecular mechanisms linking efferocytosis-related genes to therapeutic outcomes remain unclear. This study aims to investigate the role of efferocytosis in UC and the key regulatory mechanism of efferocytosis.MethodsMulti-omics integration of single-cell and bulk transcriptomic data from human UC colonic mucosa identified efferocytosis-active cellular subpopulations. Machine learning algorithms screened hub genes, followed by molecular docking to assess interactions with UST. A mouse colitis model was used to verify the inflammatory damage of UC and the key genes that play the role in efferocytosis.ResultsIn UC, the “eat me” and “digest me” signaling pathways are predominantly upregulated in myeloid cells, while the “find me” signaling cascade shows marked activation in stromal cells. Macrophages characterized by the M2 polarization demonstrate enhanced phagocytic proficiency and are instrumental in the engulfment and clearance of apoptotic cells, thereby alleviating the inflammatory cascade in UC. Six hub genes (ANXA1, PANX1, ANXA5, CD93, SERPINE1, MFGE8) were associated with UC progression and correlated with clinical response to UST. Molecular docking analysis revealed strong binding affinities between these gene-encoded proteins and UST. Transcriptomic and proteomic analyses confirmed dysregulated expression of these hub genes in the colitis model.ConclusionThis study reveals cellular heterogeneity at different stages of efferocytosis in UC, identifies efferocytosis-related genes as critical regulators of mucosal repair and predictors of UST efficacy. Findings emphasize targeting macrophage-driven efferocytosis to resolve inflammation, offering novel strategies for improving treatment outcomes.

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.

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.

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.

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.

Aquaporin-4 (AQP4) is highly polarized to perivascular astrocytic endfeet. Loss of AQP4 polarization is associated with many diseases. In Alzheimer’s disease (AD), AQP4 loses its normal location and thus reduces the clearance of amyloid-β plaques and tau protein. Clinical and experimental studies showed that moxibustion can improve the learning and memory abilities of AD. To explore whether moxibustion can affect the polarization of AQP4 around the blood-brain barrier (BBB), we used spatial transcriptomics (ST) to analyze the expression and polarization of Aqp4 in wild-type mice, APP/PS1 mice, and APP/PS1 mice intervened by moxibustion. The results showed that moxibustion improved the loss of abnormal polarization of AQP4 in APP/PS1 mice, especially in the hypothalamic BBB. Besides, the other 31 genes with Aqp4 as the core have similar depolarization in APP/PS1 mice, most of which are also membrane proteins. The majority of them have been reversed by moxibustion. At the same time, we employed the cerebrospinal fluid circulation gene set, which was found to be at a higher level in the group of APP/PS1 mice with moxibustion treatment. Finally, to further explore its mechanism, we analyzed the mitochondrial respiratory chain complex enzymes closely related to energy metabolism and found that moxibustion can significantly increase the expression of mitochondrial respiratory chain enzymes such as Cox6a2 in the hypothalamus, which could provide energy for mRNA transport. Our research shows that increasing the polarization of hypothalamic Aqp4 through mitochondrial energy supply may be an important target for moxibustion to improve cognitive impairment in APP/PS1 mice.

Irritable bowel syndrome (IBS) and ulcerative colitis (UC) are two intestinal diseases with different pathological changes. Electroacupuncture (EA) at Zusanli (ST36) on both IBS and UC is widely used in clinic practice. But it is unclear whether acupuncture at one acupoint can treat two different intestinal diseases at different layers of intestinal barrier. To address this question, we explored three intestinal barrier lesions in IBS and UC mice with the aid of transcriptome data analysis and studied the efficacy of EA at ST36 on them. The transcriptome data analysis showed that both UC and IBS had disrupted intestinal barrier in various layers. And both UC and IBS had epithelial barrier lesions with reduction of ZO-1, Occludin and Claudin-1, while UC rather than IBS had the destruction of the mucus barrier with less MUC2 expression. As to the vascular barrier, UC showed a higher CD31 level and mesenteric blood flow reduction, while IBS showed a lower PV-1 level. EA at ST36 can significantly improve the above lesions of intestinal barrier of IBS and UC. Our results gave more details about the comprehensive protective effect of EA for UC and IBS. We guess the effect of acupuncture may be a kind of homeostasis regulation.

This review outlined evidence that purinergic signaling is involved in the modulation of blood-brain barrier (BBB) permeability. The functional and structural integrity of the BBB is critical for maintaining the homeostasis of the brain microenvironment. BBB integrity is maintained primarily by endothelial cells and basement membrane but also be regulated by pericytes, neurons, astrocytes, microglia and oligodendrocytes. In this review, we summarized the purinergic receptors and nucleotidases expressed on BBB cells and focused on the regulation of BBB permeability by purinergic signaling. The permeability of BBB is regulated by a series of purinergic receptors classified as P2Y1, P2Y4, P2Y12, P2X4, P2X7, A1, A2A, A2B, and A3, which serve as targets for endogenous ATP, ADP, or adenosine. P2Y1 and P2Y4 antagonists could attenuate BBB damage. In contrast, P2Y12-mediated chemotaxis of microglial cell processes is necessary for rapid closure of the BBB after BBB breakdown. Antagonists of P2X4 and P2X7 inhibit the activation of these receptors, reduce the release of interleukin-1 beta (IL-1β), and promote the function of BBB closure. In addition, the CD39/CD73 nucleotidase axis participates in extracellular adenosine metabolism and promotes BBB permeability through A1 and A2A on BBB cells. Furthermore, A2B and A3 receptor agonists protect BBB integrity. Thus, the regulation of the BBB by purinergic signaling is complex and affects the opening and closing of the BBB through different pathways. Appropriate selective agonists/antagonists of purinergic receptors and corresponding enzyme inhibitors could modulate the permeability of the BBB, effectively delivering therapeutic drugs/cells to the central nervous system (CNS) or limiting the entry of inflammatory immune cells into the brain and re-establishing CNS homeostasis.

Myocardial ischemia(Ml)is a common disease with high mortality and morbidity worldwide.Since the pathological process of Ml is very complicated,a comprehensive un-derstanding of its pathogenesis is the key to the treatment of MI.As chromatin plays a crucial role in regulating gene expression,and gene regulation is a fundamental process in developing and disease progression,combined analysis of the chromatin and gene can further reveal the pathological mechanism of MI.

AIMS: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.MATERIALS AND METHODS: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.KEY FINDINGS: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.SIGNIFICANCE: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.

目的 采用3％乙酸(acetic acid,AA)直肠灌注联合束缚应激的方法制备腹泻型肠易激综合征(irritable bowel syndrome with diarrhea,IBS-D)小鼠模型,并评价模型的可行性.方法 雄性C57BL/6J小鼠45只,均分为健康对照组(C组)、3％乙酸组(A组)、3％乙酸+束缚组(A+R组).比较各组小鼠干预前后体重变化和存活情况,以及干预后粪便含水量、全肠道转运时间、内脏痛阈值,比较两种造模方法的优劣.观察C组和A+R组的结肠病理形态的变化,采用FD4渗透实验评价小鼠肠道粘膜完整性,ELISA法检测血清5-HT和TNF-α的含量,免疫组化法检测结肠组织中5-HTR3A的表达,明确该造模方法的病理变化特征.结果 与C组相比,A+R组的内脏痛阈值、粪便含水量显著升高(P<0.001);全肠道转运时间明显缩短(P<0.05),而A组内脏痛阈值和粪便含水量虽然也明显降低(P<0.05),但全肠道转运时间仅有变化的趋势,无显著性差异(P>0.05).A+R组血浆中FD4含量显著增加(P<0.001),血清中5-HT和TNF-α含量明显增加(P<0.05),结肠组织中5-HTR3A表达量也显著增加(P<0.001).结论 与3％乙酸灌肠相比,3％乙酸灌肠联合束缚应激的方式能较好地模拟IBS-D患者的肠道局部相关症状,并能模拟相关的病理改变.

Abstract Background Aquaporin-4 (Aqp4), a predominantly aquaporin expressed on astrocytic endfeet, has been found to be potential targets for lymphatic clearance and transcytotic delivery in the disorder of glial lymphatic system and white matter fluid metabolism impairment such as Alzheimer's disease (AD). Moxibustion is an experience-based effective treatment for AD. Exploring the large amount of complex data of Aqp4 in the processing of moxibustion may screen and provide accurate targets for prevention, ultimately leading to improve treatment options for AD. Methods The Morris water maze (MWM) was used to verify the effect of moxibustion on APP/PS1mice. Wild type mice (WT) and APP/PS1 mice before and after treatment were used for spatial transcriptomics. Aqp4 expression and perivascular polarization were quantified. Pathway enrichment was used to analyze the alteration of perivascular astrocytes and Lateral White Matter of Hypothalamus (LWMH). Immunofluorescence and transmission electron microscopy were used for protein level validation and myelin morphology observation, respectively. Results MWM testing showed an improved cognitive function of APP/PS1 mice treated with moxibustion. Among white matter regions, LWMH region of periventricular white matter was the most obvious change area of Aqp4 gene in APP/PS1 mice, and moxibustion treatment can rescue this alteration. Aqp4 mRNA and AQP4 protein located around the cerebral vessels of APP/PS1 mice decreased significantly (P < 0.01), especially in LWMH area. Moreover, the Aqp4 mRNA transport capacity of astrocytes had a reduction (P < 0.05). Meanwhile, the ion transport function closely related to AQP4 in astrocytes was also disturbed. Finally, the abnormal expression of Aqp4 and the imbalance of ion homeostasis in LWMH area, recovered after moxibustion, was closely related to the myelin injury. Conclusion Aqp4 polarized distribution in LWMH area was found to be the potential target for treating glial lymphatic disorder and white matter fluid metabolism impairment. Myelin damage in LWMH may be the following pathogenesis, which further decline the learning and memory ability such as AD.

Histone H3 lysine 4 (H3K4) methyltransferase 2D (KMT2D) plays an important role in cell development in early life. However, the function of KMT2D in adult cells such as cardiomyocytes or neurons has not been reported. In this study, cardiomyocyte-specific KMT2D knockout (KMT2D-cKO) and control (KMT2D-Ctl) mice were exposed to sham or myocardial ischemia (MI) surgery. Depletion of KMT2D aggravated the ischemic area, led to the increased mortality (26.5% in KMT2D-cKO vs 12.5% in KMT2D-Ctl) of the mice, and weakened the left ventricular systolic function. RNA-seq analysis in cardiac tissues identified genes whose expression was changed by MI and KMT2D deletion. Combined with the genome-wide association study (GWAS) analysis, cardiac disease-associated genes Rasd1, Thsd7a, Ednra, and Tns1 were identified. The expression of the Rasd1 was significantly decreased by MI or the loss of KMT2D in vivo. Meanwhile, ChIP assays demonstrated that either MI or loss of KMT2D attenuated monomethylated H3K4 (H3K4me1) enrichment on the enhancer of Rasd1. By generating a KMT2D knockout (H9C2-KO) H9C2 monoclone, we verified that the expression of Rasd1 was controlled by KMT2D, and the expression of Rasd1 was decreased by serum starvation but not low-(O2) treatment in H9C2 cells. KMT2D has a protective effect on ischemic myocardium by regulating cardiac disease-associated genes including Rasd1. KMT2D is required for the H3K4me1 deposition on the enhancer of Rasd1. Our data for the first time suggest that KMT2D-mediated Rasd1 expression may play an important protective effect on adult cells during nutritional deficiency caused by ischemic injury.

Background The pathological process of myocardial ischemia (MI) is very complicated. Acupuncture at PC6 has been proved to be effective against MI injury, but the mechanism remains unclear. This study investigated the mechanism that underlies the effect of acupuncture on MI through full-length transcriptome. Methods Adult male C57/BL6 mice were randomly divided into control, MI, and PC6 groups. Mice in MI and PC6 group generated MI model by ligating the left anterior descending (LAD) coronary artery. The samples were collected 5 days after acupuncture treatment. Results The results showed that treatment by acupuncture improved cardiac function, decreased myocardial infraction area, and reduced the levels of cTnT and cTnI. Based on full-length transcriptome sequencing, 5083 differential expression genes (DEGs) and 324 DEGs were identified in the MI group and PC6 group, respectively. These genes regulated by acupuncture were mainly enriched in the inflammatory response pathway. Alternative splicing (AS) is a post-transcriptional action that contributes to the diversity of protein. In all samples, 8237 AS events associated with 1994 genes were found. Some differential AS-involved genes were enriched in the pathway related to heart disease. We also identified 602 new genes, 4 of which may the novel targets of acupuncture in MI. Conclusions Our findings suggest that the effect of acupuncture on MI may be based on the multi-level regulation of the transcriptome.