Electroacupuncture ameliorates blood-brain barrier disruption after ischemic stroke through histone acetylation regulation at the matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 2 genes.

OBJECTIVE: To explore whether the regulation of matrix metalloproteinase 9 (MMP-9)/ tissue inhibitors of MMPs (TIMPs) gene expression through histone acetylation is a possible mechanism by which electroacupuncture (EA) protects blood-brain barrier (BBB) integrity in a middle cerebral artery occlusion (MCAO) rat model. METHODS: Male Sprague-Dawley rats were divided into four groups: the sham group, the MCAO group, the MCAO + EA (MEA) group, and the MCAO + EA + HAT inhibitor (HATi) group. The MCAO model was generated by blocking the middle cerebral artery. EA was applied to Baihui (GV20). Samples were collected 1 or 3 d after reperfusion. Neurological function scores and Evans blue extravasation were employed to evaluate the poststroke injury. The effect of EA on MMP-9/TIMPs gene expression was assessed by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and chromatin immunoprecipitation (ChIP). RESULTS: Our results showed that EA treatment prominently improved neurological function and ameliorated BBB disruption. The RT-qPCR assay showed that EA reduced the expression of MMP-9 and promoted TIMP-2 mRNA expression, but HATi reversed these effects of EA. In addition, ChIP results revealed that EA decreased the enrichment of H3K9ace/H3K27ace at MMP-9 promoters and notably stimulated the recruitment of H3K9ace/H3K27ace at TIMP-2 promoter. CONCLUSION: EA treatment at Baihui (GV20) regulates the transcription of MMP-9 and TIMP-2 through histone acetylation modification in the acute stage of stroke, which preserves the structural integrity of the BBB in MCAO rats. These findings suggested that the histone acetylation-mediated transcriptional activity of target genes may be a crucial mechanism of EA treatment in stroke.

Electroceuticals and Magnetoceuticals in Gastroenterology.

In the realm of gastroenterology, the inadequacy of current medical treatments for gastrointestinal (GI) motility disorders and inflammatory bowel disease (IBD), coupled with their potential side effects, necessitates novel therapeutic approaches. Neuromodulation, targeting the nervous system's control of GI functions, emerges as a promising alternative. This review explores the promising effects of vagal nerve stimulation (VNS), magnetic neuromodulation, and acupuncture in managing these challenging conditions. VNS offers targeted modulation of GI motility and inflammation, presenting a potential solution for patients not fully relieved from traditional medications. Magnetic neuromodulation, through non-invasive means, aims to enhance neurophysiological processes, showing promise in improving GI function and reducing inflammation. Acupuncture and electroacupuncture, grounded in traditional medicine yet validated by modern science, exert comprehensive effects on GI physiology via neuro-immune-endocrine mechanisms, offering relief from motility and inflammatory symptoms. This review highlights the need for further research to refine these interventions, emphasizing their prospective role in advancing patient-specific management strategies for GI motility disorders and IBD, thus paving the way for a new therapeutic paradigm.

Neuroprotection of Transcranial Cortical and Peripheral Somatosensory Electrical Stimulation by Modulating a Common Neuronal Death Pathway in Mice with Ischemic Stroke.

Therapeutic electrical stimulation, such as transcranial cortical stimulation and peripheral somatosensory stimulation, is used to improve motor function in patients with stroke. We hypothesized that these stimulations exert neuroprotective effects during the subacute phase of ischemic stroke by regulating novel common signaling pathways. Male C57BL/6J mouse models of ischemic stroke were treated with high-definition (HD)-transcranial alternating current stimulation (tACS; 20 Hz, 89.1 A/mm2), HD-transcranial direct current stimulation (tDCS; intensity, 55 A/mm2; charge density, 66,000 C/m2), or electroacupuncture (EA, 2 Hz, 1 mA) in the early stages of stroke. The therapeutic effects were assessed using behavioral motor function tests. The underlying mechanisms were determined using transcriptomic and other biomedical analyses. All therapeutic electrical tools alleviated the motor dysfunction caused by ischemic stroke insults. We focused on electrically stimulating common genes involved in apoptosis and cell death using transcriptome analysis and chose 11 of the most potent targets (Trem2, S100a9, Lgals3, Tlr4, Myd88, NF-kB, STAT1, IL-6, IL-1ß, TNF-α, and Iba1). Subsequent investigations revealed that electrical stimulation modulated inflammatory cytokines, including IL-1ß and TNF-α, by regulating STAT1 and NF-kB activation, especially in amoeboid microglia; moreover, electrical stimulation enhanced neuronal survival by activating neurotrophic factors, including BDNF and FGF9. Therapeutic electrical stimulation applied to the transcranial cortical- or periphery-nerve level to promote functional recovery may improve neuroprotection by modulating a common neuronal death pathway and upregulating neurotrophic factors. Therefore, combining transcranial cortical and peripheral somatosensory stimulation may exert a synergistic neuroprotective effect, further enhancing the beneficial effects on motor deficits in patients with ischemic stroke.

Effectiveness of Electroacupuncture for Managing Urinary Retention Post Lumbar Spine Surgery: a retrospective single-cohort study.

Objectives: Post-operative urinary retention (POUR) is a frequent complication following surgical procedures, characterized by an acute inability to void, leading to additional complications and extended hospitalization. Acupuncture has been shown to be effective in facilitating spontaneous urination and alleviating anxiety in patients experiencing poor urination. The present study aims to evaluate the effectiveness of electroacupuncture in the management of POUR in patients who have undergone lumbar spine surgery. Methods: This retrospective study conducted at the National Hospital of Acupuncture in Vietnam and reviewed the medical records of patients over 18 years old who underwent lumbar spine surgery and were diagnosed with POUR between January to December 2019. Electroacupuncture was administered at five specific acupuncture points Qugu (CV2), Zhongji (CV3), Zhibian (BL54), Pangguanshu (BL28), and Kunlun (BL60). This study monitored key parameters related to the effectiveness of the acupuncture treatment, including the number of acupuncture treatment sessions required until a patient was successfully treated was recorded, with a maximum of three acupuncture treatment sessions per patient, the time elapsed until urination following the treatment (minutes), and urinary bladder volume before and after treatment (mL). Results: The study demonstrated a 93.3% success rate in treating POUR with electroacupuncture. A significant reduction in post-void residual volume was noted, and patients could void within 30 minutes post-treatment. No significant differences in treatment effectiveness were observed across difference genders and age groups. Conclusion: Electroacupuncture proved to be a highly effective treatment for POUR in patients post-lumbar spine surgery, with a rapid response time and substantial reduction in PVR. However, the retrospective nature of the study and single-center focus limit its generalizability. Future research incorporating randomized controlled trials or multi-center observational studies are recommended to validate these findings and explore the potential of acupuncture in POUR management on a broader scale.

Transcriptome Analysis of the Striatum of Electroacupuncture-treated Naïve and Ischemic Stroke Mice.

Objectives: Electroacupuncture (EA) has been demonstrated to aid stroke recovery. However, few investigations have focused on identifying the potent molecular targets of EA by comparing EA stimulation between naïve and disease models. Therefore, this study was undertaken to identify the potent molecular therapeutic mechanisms underlying EA stimulation in ischemic stroke through a comparison of mRNA sequencing data obtained from EA-treated naïve control and ischemic stroke mouse models. Methods: Using both naïve control and middle cerebral artery occlusion (MCAO) mouse models, EA stimulation was administered at two acupoints, Baihui (GV20) and Dazhui (GV14), at a frequency of 2 Hz. Comprehensive assessments were conducted, including behavioral evaluations, RNA sequencing to identify differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction (PPI) network analysis, and quantitative real-time PCR. Results: EA stimulation ameliorated the ischemic insult-induced motor dysfunction in mice with ischemic stroke. Comparative analysis between control vs. MCAO, control vs. control + EA, and MCAO vs. MCAO + EA revealed 4,407, 101, and 82 DEGs, respectively. Of these, 30, 7, and 1 were common across the respective groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed upregulated DEGs associated with the regulation of inflammatory immune response in the MCAO vs. MCAO + EA comparison. Conversely, downregulated DEGs in the control vs. control + EA comparison were linked to neuronal development. PPI analysis revealed major clustering related to the regulation of cytokines, such as Cxcl9, Pcp2, Ccl11, and Cxcl13, in the common DEGs of MCAO vs. MCAO + EA, with Esp8l1 identified as the only common downregulated DEG in both EA-treated naïve and ischemic models. Conclusion: These findings underscore the diverse potent mechanisms of EA stimulation between naïve and ischemic stroke mice, albeit with few overlaps. However, the potent mechanisms underlying EA treatment in ischemic stroke models were associated with the regulation of inflammatory processes involving cytokines.

Exploring the potential effect of electroacupuncture on cardiovascular function and lipid profiles in spontaneously hypertensive rats.

Background: Investigating the effects of electroacupuncture (EA) treatment on cardiovascular function and aortic lipid profiles in spontaneously hypertensive rats (SHR) constitutes the foundational focus of this study. The overarching goal is to comprehensively elucidate the alterations brought about by EA treatment and to assess its potential as an alternative therapy for hypertension. Methods: Consecutive EA treatments were administered to SHR, and the effects on systolic blood pressure, cardiac function, and hypertension-related neuronal signals were assessed. Aortic lipid profiles in vehicle-treated SHR and EA-treated SHR groups were analyzed using mass spectrometry-based lipid profiling. Additionally, the expression of Cers2 and GNPAT, enzymes involved in the synthesis of specific aortic lipids, was examined. Results: The study demonstrated that consecutive EA treatments restored systolic blood pressure, improved cardiovascular function, and normalized hypertension-related neuronal signals in SHR. Analysis of the aortic lipid profiles revealed distinct differences between the vehicle-treated SHR group and the EA-treated SHR group. Specifically, EA treatment significantly altered the levels of aortic sphingomyelin and phospholipids, including very long-chain fatty acyl-ceramides and ether phosphatidylcholines. These changes in aortic lipid profiles correlated significantly with systolic blood pressure and cardiac function indicators. Furthermore, EA treatment significantly altered the expression of Cers2 and GNPAT. Conclusions: The findings suggest that EA may influence cardiovascular functions and aortic lipid profiles in SHR.

Neuregulin4-ErbB4 signalling pathway is driven by electroacupuncture stimulation to remodel brown adipose tissue innervation.

AIM: To show that electroacupuncture stimulation (ES) remodels sympathetic innervation in brown adipose tissue (BAT) via the bone morphogenic protein 8B (BMP8B)-neuregulin 4 (NRG4)-ErbB4 axis, with somatotopic dependence. MATERIALS AND METHODS: We established a high-fat diet (HFD) model with C57BL/6J mice to measure the thermogenesis and metabolism of BAT. In addition, the sympathetic nerve activity (SNA) was measured with the electrophysiological technique, and the immunostaining of c-Fos was used to detect the central nervous system sources of sympathetic outflows. Finally, the key role of the BMP8B-NRG4-ErbB4 axis was verified by peripheral specific antagonism of ErbB4. RESULTS: ES at the forelimb and abdomen regions significantly up-regulate SNA, whereas ES at the hindlimb region has a limited regulatory effect on SNA but still partially restores HFD-induced BAT dysfunction. Mechanistically, ES at the forelimb and abdomen regions driving catecholaminergic signals in brown adipocytes depends on neural activities projected from the ventromedial nucleus of the hypothalamus (VMH) to the spinal cord intermediolateral column (IML). Notably, the peripheral suppression of ErbB4 in BAT inhibits the thermogenesis and metabolic function of BAT, as well as significantly hindering the SNA activation and metabolic benefits induced by ES. CONCLUSION: These results suggest that ES appears to be an effective approach for remodeling sympathetic innervation in BAT, which is closely related to neuronal activity in the VMH and the NRG4-ErbB4 signaling pathway.

Electroacupuncture for slow flow/no-reflow phenomenon in patients with acute myocardial infarction undergoing percutaneous coronary intervention: protocol for a pilot randomized controlled trial.

Background: Slow flow/no-reflow (SF-NR) during percutaneous coronary intervention (PCI) is associated with poor prognosis of patients with acute myocardial infarction (AMI). Currently, effective treatment is not available for SF-NR. Electroacupuncture (EA) has shown significant efficacy as an adjuvant therapy for many cardiovascular diseases by improving microcirculation and reducing ischemia-reperfusion injury. However, its effects on SF-NR in the AMI patients during PCI are not clear. This pilot trial aims to determine the efficacy of intraoperative EA in alleviating SF-NR in AMI patients undergoing PCI. Methods: This prospective, single-center, randomized controlled, pilot trial will recruit 60 AMI patients scheduled for PCI at the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, China. The patients will be randomized in a 1:1 ratio into the EA or the control groups. Patients in the control group will undergo standard PCI. Patients in the EA group will undergo intraoperative electroacupuncture while undergoing standard PCI. Incidence of SF-NR is the primary outcome for this study. This study will also assess secondary outcomes including cardiac biomarkers, inflammatory biomarkers, pain and anxiety scores, electrocardiography parameters, traditional Chinese medicine (TCM) symptom score, and major adverse cardiovascular and cerebrovascular events (MACCE). All the included patients will undergo laboratory tests including routine blood tests, levels of electrolytes, as well as liver and renal function tests. Patients will be followed up for 1 month after the procedure. Discussion: This pilot trial will provide evidence for the potential benefits of intraoperative EA in improving microvascular perfusion and preventing or alleviating SF-NR during PCI in patients with AMI. If proven effective, intraoperative EA will provide a new and effective strategy against SF-NR and provide evidence for subsequent multicenter trials. Clinical Trial Registration: ClinicalTrials.gov, identifier (ChiCTR2300072265). Registered on 8 June 2023.

Molecular mechanism of basolateral amygdala involved in electroacupuncture-induced amelioration of cancer pain and concomitant depression based on transcriptomics techniques. / åŸºäºŽè½¬å½•ç»„å­¦æŠ€æœ¯æŽ¢è®¨åŸºåº•å¤–ä¾§æä»æ ¸å‚ä¸Žç”µé’ˆæ²»ç–—ç™Œç—›åŠå ¶è¯±å‘çš„æŠ‘éƒæƒ ç»ªçš„åˆ†å­æœºåˆ¶.

OBJECTIVES: To observe the effect of electroacupuncture (EA) of "Zusanli" (ST36) and "Sanyinjiao" (SP6) on cancer pain and concomitant negative emotion in cancer pain model mice, and to explore its molecular mechanisms in the basolateral amygdala (BLA) by using transcriptomics techniques. METHODS: C57BL/6 mice were randomized into sham operation, model and EA groups, with 10 mice in each group. The cancer pain model was established by injecting PBS suspension containing Lewis lung cancer cells into the femur. The mice in the EA group received EA stimulation(1 mA, 2 Hz) on ST36 and SP6 from the 10th day after modeling, 20 min per day for 12 successive days. The bone damage of the distal femur was observed with X-ray and H.E. staining, respectively. The mechanical pain threshold (MPT) was detected by using von Frey. The depression-like behavior was detected by using sucrose-preference test (sucrose preference index in 12 h), and the immobility (feeling of despair) duration of forced swimming within 4 min. The BLA tissue was extracted for RNA sequencing (RNA library construction, and screening differential gene profiling by transcriptomic sequencing) and bioinformatics analysis. The real-time PCR was used to validate the mRNA expression of differentially expressed genes：tumor necrosis factor superfamily 8 (Tnfsf8), bone marrow stromal cell antigen 1 (Bst1), prodynorphin (Pdyn) and voltage-gated sodium channelß4 (Scn4b). RESULTS: H.E. staining and X-ray showed significant bone damage in the distal femur in cancer pain mice. In contrast to the sham operation group, the MPT on the 1st , 4th, 7th , 10th, 14th and 21st day after modeling and sucrose preference index were significantly decreased (P<0.001, P<0.000 1), and the immobility time of the forced swimming was considerably increased in the model group (P<0.001). In contrast to the model group, the MPT values on the 14th and 21st day and sucrose preference index were obviously increased (P<0.000 1, P<0.05), and the immobility time was strikingly decreased in the EA group (P<0.01). RNA sequencing showed that a total of 404 differentially expressed genes (205 up-regulated, 199 down-regulated) were screened in the model group compared with the sham operation group, and a total of 329 differentially expressed genes (206 up-regulated and 123 down-regulated) were screened in the EA group compared with the model group. Venn diagram analysis of the differentially expressed genes showed that 45 up-regulated and 28 down-regulated genes in the model group were completely reversed by EA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the screened differentially expressed genes revealed that the above differential genes were mainly enriched in the ligand receptor activity, cytokine receptor binding, and cytokine activity related to neuro-inflammation, as well as in neuropeptide signaling pathways related to neuronal excitability, and calcium ion mediated signal transduction. The analysis of KEGG pathway showed that the differentially expressed genes were mainly enriched in the inflammation-related pathways, such as interleukin-17 pathway. Validation analysis of the differentially expressed genes showed that the expression levels of Tnfsf8 and Bst1 were significantly up-regulated in the model group compared with the sham operation group (P<0.01, P<0.05), and down-regulated by EA (P<0.01, P<0.05), while the expression levels of Pdyn and Scn4b were down-regulated in the model group in comparison with the sham operation group (P<0.01), and up-regulated by EA (P<0.05, P<0.01), which was consistent with the changing trend of the gene sequencing results. CONCLUSIONS: Acupuncture of ST36 and SP6 can significantly relieve cancer pain and concomitant negative emotion in cancer pain mice, which may be related to its functions in alleviating neuro-inflammation and relieving the abnormal activities of specific neurons in the BLA.

Effect of electroacupuncture of "Zusanli" (ST36) combined with capeOX on apoptosis and ferroptosis in nude mice with colorectal cancer. / 电针"足三里"联合capeOXæ–¹æ¡ˆå¯¹ç»“ç›´è‚ ç™Œè£¸é¼ è‚¿ç˜¤ç»†èƒžå‡‹äº¡å’Œé“æ­»äº¡çš„å½±å“.

OBJECTIVES: To investigate the impact of combined treatment of colorectal cancer (CRC) with electroacupuncture (EA) and capeOX (combined administration of fluorouracil, oxaliplatin and capecitabine) on the tumor volume, weight, spleen coefficient, apoptosis and ferroptosis of tumor tissue, and liver and kidney functions in nude mice with CRC, so as to explore its mechanisms underlying inhibiting CRC and alleviating toxic reactions of capeOX. METHODS: Female Balb/c nude mice were randomly assigned to 3 groups：model, capeOX, and EA+capeOX, with 8 nude mice in each group. The CRC model was established by subcutaneous injection of colon cancer cells at the right inguinal region. Nude mice of the capeOX group received intraperitoneal injection of oxaliplatin for 1 day and gavage of capecitabine from day 2 to day 7. EA (1 mA, 2 Hz/100 Hz) was applied to bilateral "Zusanli" (ST36) for 20 min, once daily for 7 days. During the interven-tion, the tumor volume and weight were measured every day, and at the end of intervention, the weight of the tumor tissue and spleen were measured, with tumor volume difference and spleen coefficient calculated. The proportion of apoptotic cells was measured by flow cytometry, and the contents of serum malondialdehyde (MDA), alanine aninotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were detected using ELISA. The expression level of glutathione peroxidase 4 (GPX4, a key regulator for ferroptosis) protein of the tumor tissue was determined using Western blot. RESULTS: Compared to the model group, both the capeOX group and EA+capeOX group showed a decrease in the tumor volume (on day 3 and 4 in the capeOX group, and from day 2 to 7 in the EA+capeOX group) and body weight (P<0.05, on day 3 to 7 in the EA+capeOX group and on day 2 to 7 in the capeOX group), being evidently lower in the tumor volume on day 7 in the EA+capeOX than in the capeOX group (P<0.05), and evidently higher in the body weight on day 6 and 7 in the EA+capeOX group than in the capeOX group (P<0.05). In comparison with the model group, the tumor volume difference, tumor weight and spleen coefficient in both capeOX and EA+capeOX groups were significantly decreased (P<0.05), and MDA content in EA+capeOX group was significantly decreased (P<0.05), while the contents of ALT, BUN and Cr in the capeOX group, the proportion of apoptotic cells in both capeOX and EA+capeOX groups, and the GPX4 expression level in the EA+capeOX group were all significantly increased (P<0.05). The tumor volume difference, tumor weight, and contents of MDA, ALT, AST, BUN and Cr in the EA+capeOX group were markedly lower than in the capeOX group (P<0.05), while the spleen coefficient, proportion of apoptotic cells and GPX4 expression level in the EA+capeOX group were markedly higher than those in the capeOX group (P<0.05). CONCLUSIONS: EA of ST36 can enhance the effect of capeOX in inhibiting colorectal cancer growth in nude mice with CRC, which may be related with its functions in promoting tumor cell apoptosis, inhibiting ferroptosis, and modulating immune tolerance. In addition, EA can lower the side effects of capeOX in hematopoietic and immune, liver, and kidney functions.

Effect of electroacupuncture pre-conditioning on the expression rhythm of core clock gene Bmal1 in uterine tissue of controlled hyperstimulation rats. / ç”µé’ˆé¢„å¤„ç†å¯¹ä¿ƒæŽ’åµå¤§é¼ å­å®«ç»„ç»‡æ ¸å¿ƒæ—¶é’ŸåŸºå› Bmal1表达节律的影响.

OBJECTIVES: To observe the effect of electroacupuncture (EA) pre-conditioning on the expression rhythm of clock gene Bmal1 in the uterine tissue of rats with controlled ovarian hyperstimulation(COH), so as to explore its mechanisms underlying improvement of the endometrial receptivity of ovarian superovulation during implantation. METHODS: Seventy-two female SD rats with typical estrous cycles were randomly divided into normal control, model and EA pre-conditioning (pre-EA) groups, with 24 rats in each group. The COH model was established by giving the rats with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (HCG) by intraperitoneal injection. The rats of the pre-EA group received EA stimulation (1 Hz/5 Hz, a tolerable strength) of "Guanyuan"(CV4) and "Sanyinjiao"(SP6) for 15 min each time, once daily (at 21：00 every day). After successive EA intervention during the first two estrous cycles, the modeling began in the third estrus cycle and the EA intervention was continued till the end of modeling, followed by raising the rats with superovulation induction and male rats undergoing vasoligation in one cage (1∶1). The rats during the estrum in the normal control group or those of the model group at the end of modeling were raised together with the male rats undergoing vasoligation in one cage. On the 5th day (04：00 AM) after raising in one cage, the rats in the three groups were sacrificed in six batches every 4 hours, with 4 rats in each group in each batch. The H.E. staining was used for revealing alterations of the endometrial thickness, number of glands and blood vessels and tissue histology, and ELISA employed to ascertain the contents of estradiol (E2) and progesterone (Pg) in serum. The expression rhythm of core clock gene Bmal1 ［In the present study, Zeitgeber time (ZT) is an artificially set laboratory time, i.e., ZT7 (07：00) is light on and ZT19 (19：00) is light off.］ and the expression of endometrial HoxA10 and leukemia inhibitory factor (LIF) mRNAs were detected by quantitative real-time PCR. The Western blot was employed to detect the expression levels of HoxA10 and LIF proteins. RESULTS: Findings of the clock gene Bmal1 level showed that the expression peak was at ZT12 and the valley value at ZT20 in the normal control group, and that of the peak value was at ZT20 and valley value at ZT12 in the model group, while in the pre-EA group, the peak value was at ZT8, and the valley value at ZT4. The difference of Bmal1 levels among the three groups was most significant at ZT12 (12：00), therefore, the tissue samples were taken at ZT12 in this study for comparison of the levels of different indexes among the 3 groups. Compared with the control group, the endometrial thickness, number of glands and blood vessels, HoxA10 and LIF mRNAs and proteins were significantly down-regulated (P<0.01, P<0.05), and contents of serum E2 and Pg were considerably up-regulated in the model group (P<0.01, P<0.05). Relevant to the model group, the pre-EA group had an apparent increase in the endometrial thickness, number of glands and blood vessels, and expression levels of HoxA10 and LIF mRNAs and proteins (P<0.05, P<0.01), and a marked decrease in the serum Pg (P<0.05). At the ZT12 (12：00 noon), compared with the normal control group, the mRNA level of Bmal1 was significantly decreased in the model group (P<0.01)；and compared with the model group, the level of Bmal1 mRNA was significantly increased in the pre-EA group (P<0.05). In addition, at the node of ZT16, the mRNA level of Bmal1 was significantly decreased in the model group in comparison with the normal control group (P<0.01). CONCLUSIONS: EA preconditioning can improve the endometrial receptivity during the implantation window period in rats with COH, which may be related to its functions in regulating the expression of clock gene Bmal1 in the uterine tissue and in correcting the disturbance of clock gene rhythm.

Electroacupuncture alleviates myocardial ischemia-reperfusion injury by inhibiting hypothalamic paraventricular nucleus neurons projecting to the rostral ventrolateral medulla.

Accumulating evidence suggests that electroacupuncture (EA) has obvious therapeutic effects and unique advantages in alleviating myocardial ischemia-reperfusion injury (MIRI), while the underlying neuromolecular mechanisms of EA intervention for MIRI have not been fully elucidated. The aim of the study is to investigate the role of the neural pathway of hypothalamic paraventricular nucleus (PVN) neurons projecting to the rostral ventrolateral medulla (RVLM) in the alleviation of MIRI rats by EA preconditioning. MIRI models were established by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for 2 h. Electrocardiogram recording, chemogenetics, enzyme-linked immunosorbent assay, multichannel physiology recording and haematoxylin-eosin and immunofluorescence staining methods were conducted to demonstrate that the firing frequencies of neurons in the PVN and the expression of c-Fos decreased by EA pretreatment. Meanwhile, EA preconditioning significantly reduced the levels of creatine kinase isoenzymes (CK-MB), cardiac troponin I (cTnI) and lactic dehydrogenase (LDH). Virus tracing showed a projection connection between PVN and RVLM. The inhibition of the PVN-RVLM neural pathway could replicate the protective effect of EA pretreatment on MIRI rats. However, the activation of the pathway weakened the effect of EA preconditioning. EA pretreatment alleviated MIRI by regulating PVN neurons projecting to RVLM. This work provides novel evidence of EA pretreatment for alleviating MIRI.

Identification of differentially expressed genes in the medial prefrontal cortex of rats subjected to chronic unpredictable mild stress and treated with electroacupuncture.

Major depressive disorder is a chronic mental health condition that seriously impacts afflicted individuals. Although electroacupuncture has proven to be an effective therapy for depression, its underlying biological mechanism remains largely unknown. In this study, we aimed to investigate the effects of electroacupuncture on depression-like behavior and to identify potential target genes related to those effects. To achieve this, we subjected rats to chronic unpredictable mild stress (CUMS) and used sucrose preference, forced swimming, and open-field tests to determine their depression-like behavior in the absence or after receipt of electroacupuncture treatment. RNA sequencing technology was then used to reveal the differentially expressed genes associated with depression and electroacupuncture treatment effects in the medial prefrontal cortex (mPFC). Repeated electroacupuncture treatments at the Baihui (GV20) and Taichong (LR3) acupoints significantly alleviated depression-like behavioral defects in the animals. Genomic RNA sequencing revealed several significant changes in the mPFC transcriptome of rats that received treatment. Through differential gene expression analysis, we found that electroacupuncture reversed the CUMS-induced downregulation of 46 genes and upregulation of 13 genes. Among the differentially expressed genes, Casr, Bdkrb2, Gnb3, and Ccl1 were found to be associated with depression and electroacupuncture treatment effects. In conclusion, we verified that electroacupuncture treatment has an effective antidepressant effect, and the underlying mechanism involves multiple systems and targets.

Efficacy and safety of electroacupuncture in patients with postpartum depression: a meta-analysis.

Objective: This study aimed to assess the clinical effectiveness and safety of electroacupuncture (EA) for the treatment of postpartum depression (PPD). Methods: We systematically retrieved relevant randomized controlled trials (RCTs) from electronic databases, including PubMed, Cochrane Library, China National Knowledge Infrastructure, EMBASE, China Science and Technology Journal Database, Chinese Biological Medical Database, and the Wanfang database from their inception to November 2023. The outcomes measured were the Hamilton Depression Rating Scale (HAMD) scores, Edinburgh Postnatal Depression Scale (EPDS) scores, adverse events (AEs), and the total response rate. The study aimed to estimate heterogeneity, publication bias, mean difference (MD), and risk ratios (RR) with 95% confidence intervals (CIs). Results: This study included 12 RCTs with a total of 1364 participants (571 in the treatment group and 793 in the control group) for analysis. The results of the meta-analysis indicated that EA did not significantly reduce HAMD (MD = 1.49, 95% CI = [-0.30, 3.27], P = 0.1, I2 = 0%) and EPDS (MD = 1.12, 95% CI = [-1.62, 3.85], P = 0.42, I2 = 32%) scores compared to sham EA among patients with PPD, resulting in low heterogeneity. In terms of the total response rate, the EA group exhibited superior results compared to the placebo group (RR = 1.77, 95% CI = [1.15, 2.74], P = 0.01, I2 = 0%) and the sham EA group (RR = 1.2, 95% CI = [1.02, 4.4], P = 0.02, I2 = 0%), with statistical significance and low heterogeneity. The incidence of AEs was lower, also with low heterogeneity (RR = 0.9, 95% CI = [0.57, 1.43], P = 0.66, I2 = 12%). Conclusion: The current evidence indicates that the effectiveness and safety of EA in the treatment of PPD warrant affirmation. However, EA does not demonstrate superiority over sham EA in reducing HAMD and EPDS scores in patients with PPD. Due to the limited quantity and quality of curent research, the above conclusion should be further validated through high-quality studies to confirm the efectiveness of EA in PPD management. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=318917, identifier CRD42023318917.

Effect of Specific mode electroacupuncture stimulation combined with NGF during the ischaemic stroke: Study protocol for a randomized controlled trial.

BACKGROUND: The emergence of the Nerve Growth Factor (NGF) has promoted the development of neuroprotective therapy; however, it has little effect on cerebral ischemia because of its poor Blood-Brain Barrier (BBB) permeability. Specific Mode Electroacupuncture Stimulation (SMES) can open BBB safely and effectively; however, it has shown inconclusive clinical effects and indirect clinical evidence in the recovery phase. Hence, the authors conducted a multicentre, randomized, placebo-controlled, assessor-blinded clinical trial to assess the effectiveness and safety of SMES combined with NGF treatment used during ischaemic stroke recovery. METHODS: A total of 288 stroke patients from three hospitals will be recruited and randomly allocated to four groups: acupuncture + placebo, acupuncture + NGF, SMES + placebo, and SMES + NGF, in a 1:1:1:1 ratio. Assessment data will be collected at baseline, 2-weeks, and 4-weeks during the treatment period, as well as at the 4-week and 8-week follow-up after treatment completion. The primary outcome measure will be the basic cure rate. The secondary outcome measures include the simplified Modified Barthel Index, Timed Up and Go Test, Fugl-Meyer Assessment of Motor Function Score, Tinetti Performance Oriented Mobility Assessment, Montreal Cognitive Assessment, and Loewenstein Occupational Therapy Cognitive Assessment. Moreover, resting-state functional magnetic resonance imaging and Functional near-infrared spectroscopy can detect changes in cerebral blood flow and brain function and investigate the relationship between the clinical efficacy and mechanism of the prescribed interventions. CONCLUSION: This study will provide clinical evidence for the efficacy and safety of SMES combined with NGF in the treatment of stroke patients.

Electroacupuncture improves articular microcirculation and attenuates cartilage hypoxia in a male rabbit model of knee osteoarthritis.

Background and aim: Hypoxia of the cartilage has been considered as a potential pathogenic factor in knee osteoarthritis (KOA). Studies have shown that impaired blood perfusion of joint leads to cartilage hypoxia. Electroacupuncture (EA) has proven effects on pain relief and improving microcirculation. This study aimed to explore the effect of EA on articular microcirculation and cartilage anoxic and the underlying mechanisms. Procedures: Videman's method was used for 6 weeks to establish the KOA model. EA intervention was performed in four points around the knee for 3 weeks after KOA modeling. The Lequesne MG score was used to assess ethology. We recorded the oxygen tension of synovial fluid and the synovial microcirculation in vivo. HE-staining was used to assess cartilage morphology, and immunohistochemistry (IHC), Western blotting, and RT-PCR were used to assess expression of the major glycolytic enzymes glucosetransporter1 (GLUT1), pyruvate kinase M2(PKM2), and lactate dehydrogenase A (LDHA). Enzyme-linked immunosorbent assay (Elisa) was used to detect lactate content. Results and conclusion: There was a significant decrease in Lequesne MG score and improvement in Mankin score after EA intervention (P < 0.01), a significant increase in synovial microcirculation (P < 0.05) and synovial fluid oxygen tension (P < 0.01), and there was significant decrease in the expression of GLUT1, PKM2 and LDHA (P < 0.01) and lactate (P < 0.05). This study suggested that EA ameliorate cartilage hypoxia and regulate glycolytic metabolism in chondrocytes in KOA model rabbits by improving articular microcirculation and oxygen tension.

Restoring brain health: Electroacupuncture at GB20 and LR3 for migraine mitigation through mitochondrial restoration.

BACKGROUND: Electroacupuncture (EA) is a promising alternative therapy for migraine, with mitochondrial dysfunction hypothesized as a pivotal mechanism in migraine pathophysiology. This research endeavors to investigate the therapeutic potential of EA in addressing migraines and shed light on the associated mechanisms linked to mitochondrial anomalies. MATERIALS AND METHODS: Migraine in rats was induced by 10 mg/kg nitroglycerin, followed by 2/15 Hz EA treatment at GB20 and LR3. Nociceptive behavior was recorded via a camera and analyzed using EthoVision XT 12.0 software. The hind-paw withdrawal threshold was assessed using the von Frey test. We assessed the levels of calcitonin gene-related peptide (CGRP), nitric oxide (NO), and endothelin (ET) - key parameters in migraine pathophysiology using immunohistochemistry and enzyme-linked immunosorbent assay. Mitochondrial morphology in brain tissues was observed through transmission electron microscopy. Reactive oxygen species (ROS) level in mitochondria was measured by flow cytometry. The levels of PINK1 and Parkin were assessed using Western blot analysis. RESULTS: EA at GB20 and LR3 decreased nociceptive behaviors (resting and grooming) and increased exploratory and locomotor behaviors in migraine rats. The hind-paw withdrawal threshold in migraine rats was significantly elevated following EA treatment. Post-EA treatment, levels of CGRP and NO decreased, while ET level increased, suggesting an alteration in pain and vascular physiology. Notably, EA treatment mitigated the mitochondrial damage and reduced ROS level in the brain tissues of migraine rats. EA treatment upregulated the expression of PINK1 and Parkin in migraine rats. CONCLUSION: EA at GB20 and LR3 may treat migraine by alleviating PINK1/Parkin-mediated mitochondrial dysfunction.

Exploring Mechanism of Electroacupuncture in Modulating Neuroinflammation Based on Intestinal Flora and Its Metabolites.

Neuroinflammatory responses play an important role in the pathogenesis of various diseases, particularly those affecting the central nervous system. Inhibition of neuroinflammation is a crucial therapeutic strategy for the management of central nervous system disorders. The intestinal microbial-gut-brain axis serves as a key regulatory pathway that modulates neuroinflammatory processes. Intestinal flora metabolites such as short-chain fatty acids, indoles and their derivatives, lipopolysaccharides, trimethylamine oxide, and secondary bile acids exert direct or indirect effects on neuroinflammation. Studies have shown that electroacupuncture (EA) modulates the composition of the intestinal microbiota and its metabolites, while also suppressing neuroinflammation by targeting the TLR4/NF- κ B, NLRP3/caspase-1, and microglial cell M2-type transformation pathways. This review discusses the mechanisms by which EA regulates neuroinflammation via intestinal microbiota and its metabolites, providing information and a foundation for further investigation of the precise therapeutic mechanisms of EA in neurological disorders.

Electroacupuncture at different frequencies improves visceral pain in IBS rats through different pathways.

BACKGROUND: The aim of this study was to investigate the frequency dependence of electroacupuncture (EA) in alleviating chronic visceral pain in patients with irritable bowel syndrome (IBS) and the differences in the gut microbiota and metabolites as potential mechanisms to explain frequency dependence. METHODS: A visceral hyperalgesia model was established by colorectal instillation of 2,4,6-trinitrobenzene sulfonic acid in rats, and EA treatment at 2/10 Hz, 2/50 Hz and 2/100 Hz was applied at ST25. Visceral sensation was quantified by the abdominal withdrawal reflex score and the area under the curve of the rectus abdominis electromyogram in response to colorectal distension. Ultrastructural morphological damage of colonic tissue of the rats was examined by transmission electron microscopy. 16S rRNA gene sequencing and 1H-nuclear magnetic resonance spectroscopy were applied to study the differences in the gut microbiota and to perform metabonomic profiling of the colonic tissue. KEY RESULTS: EA at ST25 at different frequencies attenuated chronic visceral pain, ultrastructural morphological damage to colonic tissue and disruption of the gut microbiota in IBS rats. The frequency of 2/100 Hz has more regulatory pathways than 2/10 Hz and 2/50 Hz. In addition, IBS rats exhibited colonic metabolic disorders, and pantothenate was significantly upregulated after EA treatment at different frequencies. Very low-density lipoprotein and 2-hydroxybutyrate were significantly increased in the 2/10 Hz group, while low density lipoprotein, very low-density lipoprotein, 2-hydroxybutyrate, methylmalonate and alpha-hydroxyisobutyric acid were significantly increased in the 2/100 Hz group. CONCLUSIONS AND INFERENCES: EA at ST25 at different frequencies attenuated chronic visceral pain through different gut microbiota and metabolic pathways.

Electroacupuncture Alleviates Memory Deficits in APP/PS1 Mice by Targeting Serotonergic Neurons in Dorsal Raphe Nucleus.

OBJECTIVE: Alzheimer's disease (AD) has become a significant global concern, but effective drugs able to slow down AD progression is still lacked. Electroacupuncture (EA) has been demonstrated to ameliorate cognitive impairment in individuals with AD. However, the underlying mechanisms remains poorly understood. This study aimed at examining the neuroprotective properties of EA and its potential mechanism of action against AD. METHODS: APP/PS1 transgenic mice were employed to evaluate the protective effects of EA on Shenshu (BL 23) and Baihui (GV 20). Chemogenetic manipulation was used to activate or inhibit serotonergic neurons within the dorsal raphe nucleus (DRN). Learning and memory abilities were assessed by the novel object recognition and Morris water maze tests. Golgi staining, western blot, and immunostaining were utilized to determine EA-induced neuroprotection. RESULTS: EA at Shenshu (BL 23) and Baihui (GV 20) effectively ameliorated learning and memory impairments in APP/PS1 mice. EA attenuated dendritic spine loss, increased the expression levels of PSD95, synaptophysin, and brain-derived neurotrophic factor in hippocampus. Activation of serotonergic neurons within the DRN can ameliorate cognitive deficits in AD by activating glutamatergic neurons mediated by 5-HT1B. Chemogenetic inhibition of serotonergic neurons in the DRN reversed the effects of EA on synaptic plasticity and memory. CONCLUSION: EA can alleviate cognitive dysfunction in APP/PS1 mice by activating serotonergic neurons in the DRN. Further study is necessary to better understand how the serotonergic neurons-related neural circuits involves in EA-induced memory improvement in AD.