Effect of ST36 electroacupuncture on the switch of skeletal muscle fibres in mice with sciatic nerve dissociation.

Skeletal muscle is striated muscle that moves autonomously and is innervated by peripheral nerves. Peripheral nerve injury is very common in clinical treatment. However, the commonly used treatment methods often focus on the regeneration of the injured nerve but overlook the pathological changes in the injured skeletal muscle. Acupuncture, as the main treatment for denervated skeletal muscle atrophy, is used extensively in clinical practice. In the present study, a mouse model of lower limb sciatic nerve detachment was constructed and treated with electroacupuncture Stomach 36 to observe the atrophy of lower limb skeletal muscle and changes in skeletal muscle fibre types before and after electroacupuncture Stomach 36 treatment. Mice with skeletal muscle denervation showed a decrease in the proportion of IIa muscle fibres and an increase in the proportion of IIb muscle fibres, after electroacupuncture Stomach 36. The changes were reversed by specific activators of p38 MAPK, which increased IIa myofibre ratio. The results suggest that electroacupuncture Stomach 36 can reverse the change of muscle fibre type from IIb to IIa after denervation of skeletal muscle by inhibiting p38 MAPK. The results provide an important theoretical basis for the treatment of clinical peripheral nerve injury diseases with electroacupuncture, in addition to novel insights that could facilitate the study of pathological changes of denervated skeletal muscle.

Electroacupuncture at ST36 acupoint regulates stem cells during experimental autoimmune encephalomyelitis.

BACKGROUND: Electroacupuncture (EA) is given to assist in the treatment of MS, which is an effective therapeutic method. However, the therapy mechanism of EA related to stem cells in the treatment of MS is not yet known. In this study, we used a classic animal model of multiple sclerosis: experimental autoimmune encephalomyelitis (EAE) to evaluate the therapeutic effect of EA at Zusanli (ST36) acupoint in EAE and shed light on its potential roles in the effects of stem cells in vivo. METHODS: The EAE animal models were established. From the first day after immunization, EAE model mice received EA at ST36 acupoint, named the EA group. The weight and clinical score of the three groups were recorded for 28 days. The demyelination, inflammatory cell infiltration, and markers of neural stem cells (NSCs), hematopoietic stem cells (HSCs), and mesenchymal stem cells (MSCs) were compared. RESULTS: We showed that EAE mice treated with EA at ST36 acupoint, were suppressed in demyelination and inflammatory cell infiltration, and thus decreased clinical score and weight loss and mitigated the development of EAE when compared with the EAE group. Moreover, our data revealed that the proportions of NSCs, HSCs, and MSCs increased in the EA group compared with the EAE group. CONCLUSIONS: Our study suggested that EA at ST36 acupoint was an effective nonpharmacological therapeutic protocol that not only reduced the CNS demyelination and inflammatory cell infiltration in EAE disease but also increased the proportions of various stem cells. Further study is necessary to better understand how EA at the ST36 acupoint affects EAE.

Acupuncture at ST36 ameliorates experimental autoimmune encephalomyelitis via affecting the function of B cells.

Acupuncture at ST36 can alleviate a variety of autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), while the specific mechanism for the treatment of EAE is not clear. In this study, we found that acupuncture at ST36 can significantly increase the excitability of splenic sympathetic nerve, and promote the differentiation of peripheral B and CD4+T cells in the anti-inflammatory direction. After blocking the splenic sympathetic nerve with 6-OHDA, this anti-inflammatory effect of acupuncture is partially reversed. In addition, the results of western blot and qPCR showed that acupuncture at ST36 simultaneously activated the ß2-AR-cAMP signaling pathway in the splenic B and CD4+T cells, and this activation was more significant in B cells. In vitro, when CD4+T cells were cultured alone, norepinephrine (NE) had no significant effect on their differentiation. While in the presence of B cells, NE significantly promotes the anti-inflammatory differentiation of B and CD4+T cells. Therefore, the above results reveal that acupuncture can relieve EAE by stimulating the sympathetic nerves of spleen, mainly through acting on B cells to mediate anti-inflammatory effects, and indirectly affecting the function of CD4+T cells.

Effects of Acupuncture on Adverse Events in Colonoscopy: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: Acupuncture has gradually penetrated into many disciplines in clinical medicine, such as surgery, anesthesia, and outpatient examinations. Although a number of clinical trials have investigated the effects of acupuncture on colonoscopy, the results were inconsistent. In this meta-analysis, we analyzed the effects of acupuncture on colonoscopy to provide evidence for subsequent research and clinical application of acupuncture in colonoscopy. METHODS: This meta-analysis was performed using Review Manager version 5.4 and Stata version 16 software. The primary outcome was the incidence of adverse events, and the secondary outcomes included patients' anxiety score before colonoscopy, time to insert the colonoscope, total detection time, propofol consumption, patients' pain score, and patient satisfaction rate. RESULTS: The results showed that the incidence of adverse events (odds ratio [OR] 0.27, 95% confidence interval [CI] 0.16-0.43, P = 0.00, I2 = 25%), patients' pain score (mean difference [MD] - 1.03, 95% CI - 1.45 to - 0.62, P = 0.00, I2 = 94%), and time to insert the colonoscope (MD = - 2.54, 95% CI - 4.96 to - 0.13, P = 0.04, I2 = 0%) were significantly lower in the treatment group than in the control group. Compared with the control group, the satisfaction rate of patients (OR 2.53, 95% CI 1.56-4.10, P = 0.00, I2 = 47%) in the treatment group was significantly improved. There was no significant between-group difference in patients' anxiety score, the total detection time, and propofol dosage. CONCLUSIONS: During colonoscopy, acupuncture can significantly reduce the incidence of adverse events, relieve patients' pain, and improve patient satisfaction. REGISTRATION: PROSPERO registration number CRD42022324428.

Anti-atherosclerotic effects of geraniin through the gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway in mice.

BACKGROUND: Cardiovascular disease is a leading cause of death, which signifies the urgent need for effective anti-atherosclerotic strategies. Gut microbiota-dependent trimethylamine-N-oxide (TMAO) is associated with atherosclerosis, and geraniin, a natural polyphenol with various biological activities, might play key role in this process. PURPOSE: We aimed to investigate the pharmacological activity of geraniin in atherosclerosis through remodeling the gut microbiota. METHODS: C57BL/6J ApoE-/- mice were administrated geraniin for 12 weeks. The colon contents were analyzed via 16S rRNA sequencing. Pathological staining was performed to evaluate the atherosclerotic characteristics. Cytokine assays detected the levels of plasma inflammatory cytokines. RAW264.7 cells were cultured in vitro and treated with TMAO. Tandem Mass Tag quantitative proteomics analysis and western blot were performed to investigate the effect of TMAO in macrophages. RESULTS: The plasma TMAO level in mice significantly decreased after geraniin intervention. The predominant intestinal microflora from geraniin-treated mice were Bacteroides (65.3%) and Firmicutes (30.6%). Pathological staining demonstrated that administration of geraniin attenuated atherosclerotic characteristics. After geraniin treatment, plasma levels of IL-1ß, IL-6, and TNF-α in mice were significantly reduced, and IL-10 levels were significantly increased. Proteomics analysis demonstrated the number of differentially expressed proteins after TMAO administration. In vitro study suggested that the atherogenic effect of TMAO could be attributed to changes in CD36, transmembrane protein 106a, apolipoprotein C1, macrophage scavenger receptor types I and II, and alpha-2-macroglobulin. CONCLUSION: Geraniin might be an effective prospective drug against cardiovascular diseases, and the gut microbiota is a potential target to reduce the risk of atherosclerotic disease.

Therapeutic Effect and Mechanism of Acupuncture in Autoimmune Diseases.

Autoimmune diseases (AIDs) are conditions arising from abnormal immune reactions to autoantigens, which can be defined as the loss of immune tolerance to autoantigens, causing the production of autoantibodies and subsequent inflammation and tissue injury. The etiology of AIDs remains elusive, which may involve both genetic and environmental factors, such as diet, drugs, and infections. Despite rapid progress in the treatment of autoimmune diseases over the past few decades, there is still no approach that can cure AIDs. As an alternative approach, traditional Chinese medicine (TCM) such as acupuncture has been used in an attempt to treat AIDs including multiple sclerosis (MS), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), and the results have proven to be quite promising, despite the fact that its mechanism is still not fully understood. In this review, the present knowledge regarding mechanisms of acupuncture in the treatment of AIDs has been summarized, and deeper insights will be provided in order to better understand how acupuncture may regulate immune responses during AIDs.

Involvement of microRNA-155 in the mechanism of electroacupuncture treatment effects on experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a neurodegenerative and demyelinating autoimmune disease mediated by autoreactive T cells that affects the central nervous system (CNS). Electroacupuncture (EA) has emerged as an alternative or supplemental treatment for MS, but the mechanism by which EA may alleviate MS symptoms is unresolved. Here, we examined the effects of EA at the Zusanli (ST36) acupoint on mice with experimental autoimmune encephalomyelitis (EAE), the predominant animal model of MS. The effects of EA on EAE emergence, inflammatory cell levels, proinflammatory cytokines, and spinal cord pathology were examined. EA treatment attenuated the EAE clinical score and associated spinal cord demyelination, while reducing the presence of proinflammatory cytokines in mononuclear cells (MNCs), downregulating microRNA (miR)-155, and upregulating the opioid peptide precursor proopiomelanocortin (POMC) in the CNS. Experiments in which cultured neurons were transfected with a miR-155 mimic or a miR-155 inhibitor further showed that the direct modulation of miR-155 levels could regulate POMC levels in neurons. In conclusion, the alleviation of EAE by EA is characterized by reduced proportions of Th1/Th17 cells and increased proportions of Th2 cells, POMC upregulation, and miR-155 downregulation, while miR-155 itself can suppress POMC expression. These results, support the hypothesis that the effects of EA on EAE may involve the downregulation of miR-155.

Network Pharmacology-Based Study on the Mechanism of Gegen Qinlian Decoction against Colorectal Cancer.

PURPOSE: Gegen Qinlian decoction (GQD) has been used to treat gastrointestinal diseases, such as diarrhea and ulcerative colitis (UC). A recent study demonstrated that GQD enhanced the effect of PD-1 blockade in colorectal cancer (CRC). This study used network pharmacology analysis to investigate the mechanisms of GQD as a potential therapeutic approach against CRC. MATERIALS AND METHODS: Bioactive chemical ingredients (BCIs) of GQD were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. CRC-specific genes were obtained using the gene expression profile GSE110224 from the Gene Expression Omnibus (GEO) database. Target genes related to BCIs of GQD were then screened out. The GQD-CRC ingredient-target pharmacology network was constructed and visualized using Cytoscape software. A protein-protein interaction (PPI) network was subsequently constructed and analyzed with BisoGenet and CytoNCA plug-in in Cytoscape. Gene Ontology (GO) functional and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis for target genes were then performed using the R package of clusterProfiler. RESULTS: One hundred and eighteen BCIs were determined to be effective on CRC, including quercetin, wogonin, and baicalein. Twenty corresponding target genes were screened out including PTGS2, CCNB1, and SPP1. Among these genes, CCNB1 and SPP1 were identified as crucial to the PPI network. A total of 212 GO terms and 6 KEGG pathways were enriched for target genes. Functional analysis indicated that these targets were closely related to pathophysiological processes and pathways such as biosynthetic and metabolic processes of prostaglandins and prostanoids, cytokine and chemokine activities, and the IL-17, TNF, Toll-like receptor, and nuclear factor-kappa B (NF-κB) signaling pathways. CONCLUSION: The study elucidated the "multiingredient, multitarget, and multipathway" mechanisms of GQD against CRC from a systemic perspective, indicating GQD to be a candidate therapy for CRC treatment.

Electroacupuncture inhibits apoptosis of splenic lymphocytes in traumatized rats through modulation of the TNF-α/NF-κB signaling pathway.

Surgical trauma leads to a severe deterioration of the immune system. Electroacupuncture (EA) may improve the immunodeficiency that occurs following surgery; however, the underlying signaling mechanisms require further study. In the present study, 40 rats were equally randomized into four groups: Control; Control + EA; Trauma; Trauma + EA. EA was applied at the 'Zusanli' (ST36) and 'Lanwei' (Extra37) acupoints, immediately following surgery. The splenic T cells were isolated from the rats 24 h after surgery. The apoptotic rate of the lymphocytes was measured by flow cytometric analysis, and western blotting was used to determine the protein expression levels of caspase-3, caspase-8, tumor necrosis factor (TNF)-α and TNF receptor 1 (TNFR1). The DNA binding activity of nuclear factor (NF)-κB was determined using Trans-AM® ELISA-based kits. The results of the present study showed that surgical trauma induced apoptosis of splenic lymphocytes, and significantly increased the protein expression levels of caspase-3 and caspase-8. This was accompanied by increased expression levels of TNF-α and TNFR1, and a marked reduction in the activity of NF-κB in splenic T cells. Administration of EA significantly decreased the expression levels of caspase-3, caspase-8, TNF-α and TNFR1, elevated the activity of NF-κB, and suppressed the apoptotic rate of the lymphocytes. The data suggests that EA may inhibit the apoptosis of splenic lymphocytes induced by surgical trauma, and ameliorate the postoperative immunosuppression. This may be mediated by the downregulation of TNF-α expression levels and upregulation of the activity of NF-κB.

Exogenous hydrogen sulfide prevents cardiomyocyte apoptosis from cardiac hypertrophy induced by isoproterenol.

Oxidative stress is a crucial factor inducing cardiomyocyte apoptosis due to cardiac hypertrophy. Additional evidence has revealed that H2S plays an antioxidant role and is cytoprotective. Hence, we aimed to elucidate whether H2S prevents cardiomyocyte apoptosis due to cardiac hypertrophy via its antioxidant function. The cardiac hypertrophy model was obtained by injecting a high dose of isoproterenol (ISO) subcutaneously, and the hemodynamic parameters were measured in groups that received either ISO or ISO with the treatment of NaHS. TUNEL (terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling) and EM (electron microscopy) experiments were performed to determine the occurrence of apoptosis in heart tissues. The expression of caspase-3 protein in the cytoplasm and NADPH oxidase 4 (NOX4), and cytochrome c (cyt c) proteins in the mitochondria were analyzed using Western blotting. In contrast, to determine whether ISO-induced apoptosis in the cultured cardiomyocytes may be related to oxidative stress, JC-1 and MitoSOX assays were performed to detect the mitochondrial membrane potential and reactive oxygen species (ROS) production in the mitochondria. Exogenous H2S was found to ameliorate cardiac function. The histological observations obtained from TUNEL and EM demonstrated that treatment with NaHS inhibited the occurrence of cardiac apoptosis and improved cardiac structure. Moreover, H2S reduced the expression of the cleaved caspase-3, NOX4 and the leakage of cyt c from the mitochondria to the cytoplasm. We also observed that exogenous H2S could maintain the mitochondrial membrane potential and reduce ROS production in the mitochondria. Therefore, H2S reduces oxidative stress due to cardiac hypertrophy through the cardiac mitochondrial pathway.

The mechanism of effective electroacupuncture on T cell response in rats with experimental autoimmune encephalomyelitis.

Previously, we demonstrated that electroacupuncture (EA) decreased lymphocyte infiltration into the spinal cords of rats presenting with experimental autoimmune encephalomyelitis (EAE), a disease model used in the study of multiple sclerosis (MS). The aim of this study was to characterize the effects of EA on the EAE. Female Lewis rats were divided into either CFA, EAE, EA, or injection with naloxone after electroacupuncture (NAL) groups. Electroacupuncture was administered every day for 21 days. To evaluate proliferation and apoptosis, lymphocytes from rats presenting with EAE were collected and cultured with ß-endorphin. Immunohistochemisty, flow cytometry and radio-immunity methods were applied to detect the expression of ß-endorphin. Results presented in this report demonstrate that the beneficial anti-inflammatory effects of EA on EAE were related to ß-endorphin production that balances the Thl/Th2 and Th17/Treg responses. These results suggest that ß-endorphin could be an important component in the development of EA-based therapies used for the treatment of EAE.

The effect of electroacupuncture on T cell responses in rats with experimental autoimmune encephalitis.

Successive electroacupuncture (EA) stimulation on Zusanli ST36 acupoints of rats with experimental autoimmune encephalitis (EAE), which is an inflammatory disease mediated by autoreactive T cells, relieved disease severity, inhibited specific T cell proliferation and rebuilt the CD4+ T cell subset balance. In addition, EA-treated rats had significantly higher ACTH concentrations in vivo compared to untreated EAE rats. These results indicated that EA stimulation could relieve the severity of EAE by restoring balance to the Th1/Th2/Th17/Treg Th cell subset responses by stimulating the hypothalamus to increase ACTH secretion.

Pseudomonas aeruginosa: mannose sensitive hemagglutinin inhibits the growth of human hepatocarcinoma cells via mannose-mediated apoptosis.

A vaccine derived from the outer membrane proteins of the Gram-negative bacterium Pseudomonas aeruginosa has been shown to have immune modulatory properties. An inactivated mutant strain of P. aeruginosa with mannose sensitive hemagglutinin fimbria (PA-MSHA) has been used for adjuvant therapy for malignant cancer. In this study, the growth of human hepatocellular carcinoma Hep G2 and BEL-7402 cells is inhibited by PA-MSHA, but not by mannose-cleaved PA-MSHA. PA-MSHA-treated cells arrested in the S phase of the cell cycle and underwent apoptosis. We hypothesize that apoptosis induced by treatment of Hep G2 and BEL-7402 cells with PA-MSHA is mediated by the mannose residues of PA-MSHA and is propagated through the extrinsic apoptosis pathway directly through caspase-8. These data provide mechanistic details for the potential application of PA-MSHA-based treatment of hepatocellular carcinoma.