Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Child ; Consensus ; Autoimmune Diseases of the Nervous System/drug therapy* ; Autoimmune Diseases/drug therapy* ; Nervous System Diseases/drug therapy*

Extracellular vesicles (EVs), nanoscale lipid bilayer vesicles actively secreted by organisms into the extracellular environment, are rich in specific bioactive substances, such as proteins, genetic materials and lipids. These vesicles are involved in intercellular interactions and can pass through the blood-brain barrier, and may thus potentially serve as important biological substances for treatment of neurological diseases. In this review, we summarize the biological origin of EVs and their therapeutic potential in neurological diseases, expound the possibility of EV-based treatment of neurological diseases using traditional Chinese medicine, and discuss the challenges and prospects of researches of EVs for the treating neurological diseases.
Extracellular Vesicles ; Humans ; Nervous System Diseases/therapy* ; Medicine, Chinese Traditional

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

Leonurus japonicas Houtt., has been recorded as "light body and long life" properties in the oldest classical medicinal book Shennong Bencao Jing thousands of years ago. Herba leonuri, also named Chinese Motherwort or Siberian Motherwort, has the effects of activating blood circulation, regulating menstruation, diuresis and detumescence, clearing heat and detoxifying, and is known as the "sacred medicine of gynecology." It has been well known by doctors and usually used in the treatment of common gynecological diseases in clinic. Leonurine is a very important alkaloid in Herba leonuri, which has many biological activities such as anti-oxidation, anti-inflammation, and anti-apoptosis. Diseases of the cardiovascular system and central nervous system are "major health threats" that threaten human life and health worldwide, however, many drugs have certain side effects right now. This paper reviews the potential molecular therapeutic effects of leonurine on cardiovascular system and central nervous system diseases, highlights the current findings of research progress, and focuses on the therapeutic effects of leonurine in various diseases. At present, leonurine is in the stage of clinical experiment, and we hope that our summary can provide guidance for its future molecular mechanism study and clinical application.
Humans ; Gallic Acid/therapeutic use* ; Leonurus/chemistry* ; Cardiovascular Diseases/drug therapy* ; Animals ; Central Nervous System Diseases/drug therapy*

OBJECTIVE: Diabetes-induced gastrointestinal (GI) motility disorders are increasingly prevalent. Damage to the enteric nervous system (ENS), composed primarily of enteric neurons and glial cells, is an essential mechanism involved in these disorders. Although electroacupuncture (EA) has shown the potential to mitigate enteric neuronal loss, its mechanism is not fully understood. Additionally, the effects of EA on enteric glial cells have not been investigated. Enteric neural precursor cells (ENPCs) contribute to the structural and functional integrity of the ENS, yet whether EA enhances their differentiation into enteric neurons and glial cells remains unexplored. This study investigates whether EA promotes ENS repair through enhancing ENPC-derived neurogenesis and gliogenesis and elucidates the potential molecular mechanisms involved. METHODS: Transgenic mice were used to trace Nestin⁺/nerve growth factor receptor (Ngfr)⁺ ENPCs labeled with green fluorescent protein (GFP) in vivo. Mice were randomly divided into four groups: control, diabetes mellitus (DM), DM + sham EA, and DM + EA. The effects of EA on diabetic mice were evaluated by GI motility, ENS structure, and ENPC differentiation. Glial cell line-derived neurotrophic factor (GDNF)/Ret signaling was detected to clarify the underlying molecular mechanisms. RESULTS: EA alleviated diabetes-induced GI motility disorders, as indicated by reduced whole gut transit time, shortened colonic bead expulsion time, and enhanced smooth muscle contractility. Furthermore, EA attenuated diabetes-induced losses of enteric neurons and glial cells, thereby restoring ENS integrity. Notably, EA reversed the diabetes-induced decrease in ENPCs and significantly increased the absolute number and the proportion of ENPC-derived enteric neurons. However, immunofluorescence analyses revealed no colocalization between EA-induced glial fibrillary acidic protein⁺ glial cells and GFP-labeled ENPCs. Mechanistically, GDNF/Ret signaling was elevated in intestinal tissues and upregulated in ENPCs in EA-treated diabetic mice. CONCLUSION EA facilitates ENS repair by promoting Nestin⁺/Ngfr⁺ ENPC differentiation into enteric neurons via upregulation of GDNF/Ret signaling, and driving enteric gliogenesis from non-Nestin⁺/Ngfr⁺ ENPCs. These findings highlight EA's role in ameliorating diabetes-induced GI dysmotility through ENPC-derived ENS restoration. Please cite this article as: Guo JL, Liu S, Ding SJ, Yang X, Du F. Electroacupuncture at ST36 improves gastrointestinal motility disorders by promoting enteric nervous system regeneration through GDNF/Ret signaling in diabetic mice. J Integr Med. 2025; 23(5):548-559.
Animals ; Electroacupuncture ; Enteric Nervous System/physiology* ; Gastrointestinal Motility/physiology* ; Glial Cell Line-Derived Neurotrophic Factor/metabolism* ; Diabetes Mellitus, Experimental/therapy* ; Signal Transduction ; Mice ; Gastrointestinal Diseases/physiopathology* ; Proto-Oncogene Proteins c-ret/metabolism* ; Mice, Transgenic ; Male ; Nerve Regeneration ; Neural Stem Cells ; Mice, Inbred C57BL ; Acupuncture Points

Antisense oligonucleotide (ASO) was discovered several decades ago and initially used only as a research tool in the laboratory. In recent years, several ASO therapeutics have been developed for neurological disorders. Some of these therapeutics, including eteplirsen, golodirsen, viltolarsen, nusinersen and inotersen, have been approved by the Food and Drug Administration (FDA) and begun to draw the public's attention as an effective therapeutic approach. These novel therapeutics have shown great performance, while many similar therapeutics are under investigation and in clinical trials. This n-of-1 precision medicine may start a new chapter in the paradigm of therapeutics. Clinicians, clinical geneticists, and genetic counselors may know about this novel therapy, but very few may understand the background in details. During genetic counseling, they have the responsibility to convey the effectiveness, side effects and cost of such therapies to patients and their families. As these target therapies will require precise genetic diagnosis before treatment, healthcare professionals and genetic counselors play a vital role in relating the patients to the corresponding ASO drugs. This review has elaborated the mechanism of ASO therapies, including basic rationales, modifications, side effects and delivery routes. It also systemically summarized the FDA-approved ASO therapeutics and their applications for various neurological disorders, and discussed the limitations and challenges the real-world market may face and issues genetic counselor should take into consideration in the near future.
Humans ; Oligonucleotides, Antisense/therapeutic use* ; Nervous System Diseases/drug therapy* ; Genetic Therapy/methods*

OBJECTIVE: To investigate the clinical effect of electroacupuncture (EA) in preventing chemotherapy-induced peripheral neuropathy (CIPN). METHODS: Fifty-two patients with breast cancer in the regimen of taxane-assisted/neoadjuvant chemotherapy, were randomly divided into an EA group (26 cases, 3 cases dropped out) and a usual care (UC) group (26 cases, 1 case dropped out). In the UC group, on the basis of standard chemotherapy regimen, the routine nursing was administered. In the EA group, on the intervention as the UC group, EA was added, the acupoints included Yintang (GV 24⁺), Baxie (EX-UE 9, the second one), Waiguan (TE 5), Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36), Yinlingquan (SP 9), Sanyinjiao (SP 6), Taixi (KI 3), Taichong (LR 3), Xuanzhong (GB 39) and Bafeng (EX-LE 10, the fourth one). Electric stimulation was attached to Taichong (LR 3) and Sanyinjiao (SP 6) on the same side, with disperse-dense wave and the frequency of 2 Hz/10 Hz, for 30 min. EA started one day before the first cycle of chemotherapy, twice weekly in the first two weeks and once weekly in the rest weeks of chemotherapy. The duration of the intervention with EA was 12 weeks. The incidence of CIPN was compared in week 24 of the trial between the two groups. At the baseline and in week 12 and 24 of the trial, the score of EORTC QLQ-CIPN20 (European Organization for Research and Treatment of Cancer on chemotherapy-induced peripheral nerve toxicity quality of life questionnaire 20), the score of TCM syndrome scale and the score of EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer on quality of life scale) were observed in the two groups. At the baseline and in week 12 of the trial, the sensory nerve conduction velocity (SCV) and the motor nerve conduction velocity (MCV) was detected. RESULTS: In week 24 of the trial, the incidence of CIPN was 17.4% (4/23) in the EA group, lower than that (72.0%, 18/25) in the UC group (P<0.001). The incidence of high-grade CIPN was 0% (0/23) in the EA group, lower than that (28.0%, 7/25) in the UC group (P<0.05). In week 12 and 24 of the trial, the scores for the sensory nerve symptom of EORTC QLQ-CIPN20 and the total scores were higher when compared with the baseline in the UC group (P<0.001, P<0.05, P<0.01). In week 24 of the trial, the score for the sensory nerve symptom of EORTC QLQ-CIPN20 in the EA group was lower than that of the UC group (P<0.05). In week 12 of the trial, SCV of the right superficial peroneal nerve was reduced when compared with the baseline in the UC group (P<0.05), and SCV of the left median nerve and the right superficial peroneal nerve was higher in the EA group when compared with the UC group (P<0.05, P<0.01). In week 12 and 24 of the trial, the scores for the secondary symptoms of TCM scale were decreased in the EA group compared with the baseline (P<0.05), and the scores for the primary and secondary symptoms, as well as the total scores of TCM scale were all higher than those of the baseline in the UC group (P<0.01, P<0.001, P<0.05). In week 12 of the trial, the scores for the primary and secondary symptoms, as well as the total score of TCM scale in the EA group were lower than those of the UC group (P<0.05, P<0.01). In week 24 of the trial, the score for the secondary symptoms and the total score of TCM scale in the EA group were lower than those of the UC group (P<0.05). In week 12 of the trial, the scores for fatigue, pain, nausea and vomiting in EORTC QLQ-C30 were increased in comparison with the baseline in the UC group (P<0.05, P<0.01); in week 24 of the trial, the score of the general health in EORTC QLQ-C30 was elevated when compared with the baseline in the EA group (P<0.001), and the scores for nausea and vomiting, loss of appetite were decreased in comparison with the baseline (P<0.01). In week 12 of the trial, the score of the general health in EORTC QLQ-C30 in the EA group was higher compared with the UC group (P<0.01), and the scores for pain, nausea and vomiting were lower (P<0.01, P<0.05). In week 24 of the trial, the score of the general health in EORTC QLQ-C30 was higher in the EA group compared with the UC group (P<0.001), and the score for loss of appetite was lower (P<0.05). CONCLUSION Electroacupuncture reduces the incidence and severity of CIPN, ameliorates nerve conduction velocity and improves the quality of life of the patients.
Humans ; Electroacupuncture ; Female ; Peripheral Nervous System Diseases/prevention & control* ; Middle Aged ; Adult ; Breast Neoplasms/therapy* ; Antineoplastic Agents/adverse effects* ; Aged

OBJECTIVE: To investigate the effect of hyperbaric oxygen (HBO) on paroxysmal sympathetic hyperexcitation (PSH) after brain injury. METHODS: A multicenter retrospective study was conducted. Fifty-six patients with PSH who received HBO treatment from four hospitals in Henan Province from January 2021 to September 2023 were selected as the HBO group, and 36 patients with PSH who did not receive HBO treatment from Zhengzhou People's Hospital from May 2018 to December 2020 were selected as the control group. PSH assessment measure (PSH-AM) score [clinical feature scale (CFS) score+diagnostic likelihood tool (DLT) score] and Glasgow coma scale (GCS) were compared before and after HBO treatment, and between HBO group and control group to evaluate the effect of HBO treatment on prognosis of PSH patients. RESULTS: There were no statistically significant differences in age, gender, PSH etiology, GCS score, time from onset to occurrence of PSH, CFS score, CFS+DLT score and frequency of PSH episodes between the two groups, indicating comparability. The duration of HBO treatment ranged from 3 to 11 days for 56 patients receiving HBO treatment, and the duration of HBO treatment ranged from 3 to 5 courses. Compared with before treatment, after HBO treatment, PSH symptoms in HBO patients were significantly relieved (body temperature increase: 14.29% vs. 64.29%, heart rate increase: 25.00% vs. 98.21%, shortness of breath: 14.29% vs. 76.79%, blood pressure increase: 8.93% vs. 85.71%, sweating: 10.71% vs. 85.71%, muscle tone increased: 19.64% vs. 75.00%, all P < 0.05), CFS+DLT score decreased significantly (16.90±4.81 vs. 22.12±3.12, P < 0.01), GCS score improved (12.31±5.34 vs. 5.95±2.18, P < 0.01). After 30 days of hospitalization, compared with the control group, PSH symptoms in the HBO group were improved (body temperature increase: 14.29% vs. 19.44%, heart rate increase: 19.64% vs. 25.00%, shortness of breath: 10.71% vs. 27.78%, blood pressure increase: 7.14% vs. 22.22%, sweating: 8.93% vs. 25.00%, muscle tone increased: 19.64% vs. 38.89%, all P < 0.05 except body temperature increase), CFS+DLT score decreased (16.90±3.81 vs. 19.98±4.89, P < 0.05), GCS score increased (14.12±4.12 vs. 12.31±4.14, P < 0.01), the length of intensive care unit (ICU) stay was shortened (days: 18.01±5.67 vs. 24.93±8.33, P < 0.01). CONCLUSIONS HBO treatment can significantly relieve the symptoms of patients with PSH after brain injury and provide a new idea for the treatment of PSH patients.
Humans ; Hyperbaric Oxygenation/methods* ; Retrospective Studies ; Brain Injuries/therapy* ; Female ; Male ; Prognosis ; Glasgow Coma Scale ; Autonomic Nervous System Diseases/etiology*

As prominent immune cells in the central nervous system, microglia constantly monitor the environment and provide neuronal protection, which are important functions for maintaining brain homeostasis. In the diseased brain, microglia are crucial mediators of neuroinflammation that regulates a broad spectrum of cellular responses. In this review, we summarize current knowledge on the multifunctional contributions of microglia to homeostasis and their involvement in neurodegeneration. We further provide a comprehensive overview of therapeutic interventions targeting microglia in neurodegenerative diseases. Notably, we propose microglial depletion and subsequent repopulation as promising replacement therapy. Although microglial replacement therapy is still in its infancy, it will likely be a trend in the development of treatments for neurodegenerative diseases due to its versatility and selectivity.
Humans ; Microglia/physiology* ; Central Nervous System ; Neurodegenerative Diseases/therapy* ; Brain/physiology* ; Homeostasis

Serum and glucocorticoid-regulated kinase 1 (SGK1) plays an important role in the physiological processes of hormone release, neuronal excitation and cell proliferation. SGK1 also participates in the pathophysiological processes of inflammation and apoptosis in the central nervous system (CNS). Increasing evidence demonstrates that SGK1 may serve as a target of the intervention of neurodegenerative diseases. In this article, we summarize the recent progress on the role and molecular mechanisms of SGK1 in the regulation of the function of the CNS. We also discuss the potential of newly discovered SGK1 inhibitors in the treatment of CNS diseases.
Humans ; Cell Proliferation ; Central Nervous System Diseases/drug therapy* ; Inflammation ; Protein Serine-Threonine Kinases/physiology*