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Salsolinol as an RNA m~6A methylation inducer mediates dopaminergic neuronal death by regulating YAP1 and autophagy

Neural Regeneration Research 2025年第3期20卷 887-899页

作者： Jianan Wang Yuanyuan Ran Zihan Li Tianyuan Zhao Fangfang Zhang Juan Wang Zongjian Liu Xuechai Chen Beijing International Science and Technology Cooperation Base for Antiviral Drugs College of Chemistry and LifeBeijing University of TechnologyBeijingChina Department of rehabilitation Beijing Rehabilitation HospitalCapital Medical UniversityBeijingChina

Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environmental toxin that causes Parkinson's ***,the mechanism by which Sal mediates dopaminergic neuronal death remains *** this study,we found that Sal significantly enhanced the global level of N~6-methyladenosine(m~6A)RNA methylation in PC12 cells,mainly by inducing the downregulation of the expression of m~6A demethylases fat mass and obesity-associated protein(FTO)and alk B homolog 5(ALKBH5).RNA sequencing analysis showed that Sal downregulated the Hippo signaling *** m~6A reader YTH domain-containing family protein 2(YTHDF2)promoted the degradation of m~6A-containing Yes-associated protein 1(YAP1)mRNA,which is a downstream key effector in the Hippo signaling ***,downregulation of YAP1 promoted autophagy,indicating that the mutual regulation between YAP1 and autophagy can lead to *** findings reveal the role of Sal on m~6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and *** results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.

关键词： ALKBH5 autophagy FTO Hippo pathway m~6A Parkinson's disease RNA methylation salsolinol YAP1 YTHDF2

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Advances in therapies using mesenchymal stem cells and their exosomes for treatment of peripheral nerve injury:state of the art and future perspectives

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Neural Regeneration Research 2025年第11期20卷 3151-3171页

作者： Fatima Aldali Chunchu Deng Mingbo Nie Hong Chen Department of rehabilitation Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Department of Orthopedics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

“Peripheral nerve injury”refers to damage or trauma affecting nerves outside the brain and spinal *** nerve injury results in movements or sensation impairments,and represents a serious public health *** severed peripheral nerves have been effectively joined and various therapies have been offered,recovery of sensory or motor functions remains limited,and efficacious therapies for complete repair of a nerve injury remain *** emerging field of mesenchymal stem cells and their exosome-based therapies hold promise for enhancing nerve regeneration and *** stem cells,as large living cells responsive to the environment,secrete various factors and *** latter are nano-sized extracellular vesicles containing bioactive molecules such as proteins,microRNA,and messenger RNA derived from parent mesenchymal stem *** have pivotal roles in cell-to-cell communication and nervous tissue function,offering solutions to changes associated with cell-based *** ongoing investigations,mesenchymal stem cells and mesenchymal stem cell-derived exosome-based therapies are in the exploratory stage.A comprehensive review of the latest preclinical experiments and clinical trials is essential for deep understanding of therapeutic strategies and for facilitating clinical *** review initially explores current investigations of mesenchymal stem cells and mesenchymal stem cell-derived exosomes in peripheral nerve injury,exploring the underlying ***,it provides an overview of the current status of mesenchymal stem cell and exosomebased therapies in clinical trials,followed by a comparative analysis of therapies utilizing mesenchymal stem cells and ***,the review addresses the limitations and challenges associated with use of mesenchymal stem cell-derived exosomes,offering potential solutions and guiding future directions.

关键词： clinical trials exosome extracellular vesicles mesenchymal stem cells nerve regeneration peripheral nerve injury pre-clinical experiments

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Altered Brain Regional Homogeneity Following Contralateral acupuncture at Quchi (LI 11) and Zusanli (ST 36) in Ischemic Stroke Patients with Left Hemiplegia: An fMRI Study

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Chinese Journal of Integrative Medicine 2020年第1期26卷 20-25页

作者： CHEN Shu-qi CAI De-chun CHEN Ji-xin YANG Han LIU Lian-sheng medical Imaging Department The First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou510405China medical college of acu・moxi and rehabilitation Guangzhou University of Chinese MedicineGuangzhou510006China Artemisinin Research Center Guangzhou University of Chinese Medicine510006China The Second Clinical college Guangzhou University of Chinese MedicineGuangzhou510006China

Objective: To study the effect of contralateral acupuncture(CAT) at acupoints of Quchi(LI 11) and Zusanli(ST 36) on the unaffected limbs of ischemic stroke patients with left hemiplegia based on regional homogeneity(ReHo) indices. Methods: Ten ischemic stroke patients with left hemiplegia received CAT on right side at LI 11 and ST 36. Functional magnetic resonance imaging(fMRI) was performed before and after acupuncture. A ReHo analytical method was used to compare brain responses of patients before and after CAT operated by REST software. Results: The stimulation at both LI 11 and ST 36 on the unaffected limbs produced significantly different neural activities. CAT elicited increased ReHo values at the right precentral gyrus and superior frontal gyrus, decreased ReHo value at right superior parietal lobule, left fusiform gyrus and left supplementary motor area. Conclusions: acupuncture at one side could stimulate bilateral regions. CAT could evoke the gyrus which was possibly related to motor recovery from stroke. A promising indicator of neurobiological deficiencies could be represented by ReHo values in post-stroke patients.

关键词： contralateral acupuncture ischemic stroke functional magnetic resonance imaging regional homogeneity

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Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

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Neural Regeneration Research 2025年第5期20卷 1445-1454页

作者： Meifeng Zheng Borui Zhang Sonata S Y Yau Kwok-Fai So Li Zhang Haining Ou Department of rehabilitation Medicine Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of rehabilitation Medicine The Fifth Clinical College of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Key Laboratory of CNS Regeneration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina Department of rehabilitation Sciences The Hong Kong Polytechnic UniversityHong Kong Special Administrative RegionChina State Key Laboratory of Brain and Cognitive Science Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Center for Exercise and Brain Science School of PsychologyShanghai University of SportShanghaiChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug *** exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after *** this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral *** also examined the role of exercise-induced circulating factors in these *** mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery *** found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory *** analysis showed that circulating adiponectin plays a critical role in these preventive effects of *** activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise *** summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

关键词： adiponectin cerebral ischemia exercise pre-conditioning hippocampus memory function middle cerebral artery occlusion prefrontal cortex synaptic proteins treadmill exercise

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Comprehensive bibliometric analysis of pharmacotherapy for bipolar disorders:Present trends and future directions

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World Journal of Psychiatry 2025年第1期15卷 153-167页

作者： Bo-Fan Chen Li Liu Fang-Zhen Lin Hai-Min Zeng Hai-Qiang Huang Chun-Fang Zhang Cong-Cong Liu Xiang Chen Jie Peng Yun-Fa Wang Zhi-Lin Wang Bin Chen De-Le Liu Yun Liu Zheng-Zheng Li Xin-Xing Zeng The Second Affiliated Hospital Jiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina The Second Clinical medical college Jiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina Department of rehabilitation Medicine The Second Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina Jiangxi Provincial People’s Hospital The First Affiliated Hospital of Nanchang Medical CollegeNanchang 330006Jiangxi ProvinceChina Department of Psychiatry Jiangxi Mental HospitalHospital of Nanchang UniversityNanchang UniversityNanchang 330029Jiangxi ProvinceChina

BACKGROUND Bipolar disorder(BD)is a severe mental illness characterized by significant mood *** drug treatment modalities are crucial for managing *** To analyze the current status and future trends of global research on BD drug treatment over the last *** The Web of Science Core Collection database spanning from 2015 to 2024 was utilized to retrieve literature related to BD drug treatment.A total of 2624 articles were *** visualization and analysis were conducted using CiteSpace,VOSviewer,Pajek,Scimago Graphica,and R-studio bibliometrix to identify RESULTS The United States,China,and the United Kingdom have made the most significant contributions to research on BD drug treatment and formed notable research collaboration *** University of Pittsburgh,Massachusetts General Hospital,and the University of Michigan have been identified as the major research institutions in this *** Journal of Affective Disorders is the most influential journal.A keyword analysis revealed research hotspots related to clinical symptoms,drug efficacy,and genetic mechanisms.A citation analysis identified the management guidelines published by Yatham et al in 2018 as the most cited *** This study provides a detailed overview of the field of BD drug treatment,highlighting key contributors,research hotspots,and future *** study findings can be employed as a reference for future research and policymaking,which may enable further development and optimization of BD pharmacotherapy.

关键词： Bipolar disorder Drug treatment Bibliometric analysis Visualization Mental disorder

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Efficacy and safety of non-pharmacological interventions for irritable bowel syndrome in adults

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World Journal of Gastroenterology 2020年第41期26卷 6488-6509页

作者： Yun-Kai Dai Yun-Bo Wu Ru-Liu Li Wei-Jing Chen Chun-Zhi Tang Li-Ming Lu Ling Hu Institute of Gastroenterology Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina medical college of acu-moxi and rehabilitation Guangzhou University of Chinese MedicineGuangzhou 510000Guangdong ProvinceChina

BACKGROUND Although nonpharmacological interventions(NPI) for irritable bowel syndrome(IBS) have been applied clinically, their relative efficacy and safety are poorly *** To compare and rank different NPI in the treatment of *** Five electronic databases were searched from their inception to January 12, 2020. Data of included publications were analyzed using network meta-analysis(NMA). Quality of endpoints were assessed by tools of the Cochrane Handbook and the GRADEpro software. Pooled relative risk or standardized mean difference with their corresponding 95% confidence intervals were used for statistical analysis. Surface under the cumulative ranking curve(SUCRA) probability value was conducted to rank the examined interventions. Sensitivity analysis was performed to verify the robustness of results and test the source of *** Forty randomized controlled trials with 4196 participants were included in this NMA. Compared with routine pharmacotherapies and placebo, acupuncture and cognitive behavioral therapy(CBT) had better efficacy in relieving IBS symptoms. Based on the SUCRA values, acupuncture ranked first in improving overall clinical efficacy and avoiding adverse effects. CBT ranked first in lowering the scores of IBS symptom severity scale, self-rating anxiety scale and self-rating depression *** This study confirmed the efficacy and safety of NPI for improving IBS symptoms, which to some extent recommended several interventions for clinical practice.

关键词： Nonpharmacological interventions Irritable bowel syndrome Network meta-analysis Randomized controlled trials Adults Clinical practice

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Enriched environment enhances histone acetylation of NMDA receptor in the hippocampus and improves cognitive dysfunction in aged mice

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Neural Regeneration Research 2020年第12期15卷 2327-2334页

作者： Xin Wang Zhao-Xiang Meng Ying-Zhu Chen Yu-Ping Li Hong-Yu Zhou Man Yang Ting-Ting Zhao Yu-Lai Gong Yi Wu Tao Liu Department of rehabilitation Medicine Huashan HospitalFudan UniversityShanghaiChina Department of rehabilitation Clinical Medical CollegeYangzhou UniversityYangzhouJiangsu ProvinceChina Department of rehabilitation First Affiliated HospitalDalian Medical UniversityDalianLiaoning ProvinceChina Department of rehabilitation Medicine Sichuan Provincial Rehabilitation Hospital Affiliated to Chengdu University of TCMChengduSichuan ProvinceChina South China Research Center for acupuncture and moxibustion Medical College of Acu-Moxi and RehabilitationGuangzhou University of Chinese MedicineGuangzhouGuangdong ProvinceChina

The mechanisms of age-associated memory impairment may be associated with glutamate receptor function and chromatin *** observe the effect of an enriched environment on the cognitive function of mice with age-associated memory impairment,3-monthold C57BL/6 male mice("young"mice)were raised in a standard environment,while 24-month-old C57BL/6 male mice with memory impairment("age-associated memory impairment"mice)were raised in either a standard environment or an enriched *** enriched environment included a variety of stimuli involving movement and sensation.A water maze test was then used to measure cognitive function in the ***,quantitative real-time polymerase chain reaction and western blot assays were used to detect right hippocampal GluN2B mRNA as well as protein expression of GluN2B and CREB binding protein in all *** addition,chromatin immunoprecipitation was used to measure the extent of histone acetylation of the hippocampal GluN2B gene *** with the young mice,the water maze performance of age-associated memory impairment mice in the standard environment was significantly *** addition,there were significantly lower levels of total histone acetylation and expression of CREB binding protein in the hippocampus of age-associated memory impairment mice in the standard environment compared with the young *** were also significantly lower levels of histone acetylation,protein expression,and mRNA expression of GluN2B in the hippocampus of these *** contrast,in the age-associated memory impairment mice with the enriched environment intervention,the water maze performance and molecular biological indexes were significantly *** data confirm that an enriched environment can improve cognitive dysfunction in age-associated memory impairment mice,and suggest that the mechanisms may be related to the increased expression of CREB binding protein and the increased degree of total histone a

关键词： brain central nervous system factor in vitro model mice recovery regenerations protein

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A novel flexible nerve guidance conduit promotes nerve regeneration while providing excellent mechanical properties

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Neural Regeneration Research 2025年第7期20卷 2084-2094页

作者： Tong Li Quhan Cheng Jingai Zhang Boxin Liu Yu Shi Haoxue Wang Lijie Huang Su Zhang Ruixin Zhang Song Wang Guangxu Lu Peifu Tang Zhongyang Liu Kai Wang Department of Orthopedics the Fourth Medical Center of Chinese PLA General HospitalBeijingChina Department of Training and Sports Medicine Characteristic Medical Center of Chinese People’s Armed Police ForceTianjinChina medical School of Chinese PLA BeijingChina Key Laboratory of Bioactive Materials for the Ministry of Education College of Life SciencesNankai UniversityTianjinChina Department of Orthopedics Tianjin HospitalTianjinChina Department of rehabilitation Medicine Er Quan Hospital of PAPWuxiJiangsu ProvinceChina

Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor *** an alternative,nerve guidance conduits may be *** ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve *** designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align ***,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber *** presence of aligned fibers on the inner surface can promote the extension of nerve cells along the *** helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide *** novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.

关键词： aligned fibers anti-kinking helical fibers nerve guidance conduit nerve regeneration peripheral nerve injury topological guidance

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Immunopotentiator Thymosin Alpha-1 Promotes Neurogenesis and Cognition in the Developing Mouse via a Systemic Th1 Bias

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Neuroscience Bulletin 2017年第6期33卷 675-684页

作者： Ge Wang Fen He Yunlong Xu Yuwei Zhang Xiao Wang Chunhua Zhou Yihong Huang Juntao Zou Department of Anatomy and Neurobiology Zhongshan School of Medicine Sun Yat-Sen University Department of Radiation Oncology First Affiliated HospitalGuangzhou Medical University South China Research Center for acupuncture and moxibustion Medical College of Acu-Moxi and RehabilitationGuangzhou University of Chinese Medicine Department of Anatomy Wannan Medical College Department of Neurology The Fifth Affiliated Hospital of Southern Medical University

In early life, the immune system plays an essential role in brain development. In our study, the immunopotentiator thymosin alpha-1（Ta1） was peripherally administered to neonatal mice to explore whether the peripheral immunopotentiator affects neurodevelopment and cognition, and to further investigate the relevant mechanism. Compared with the control group, the Ta1 mice displayed better cognitive abilities in early life. The numbers of 5-bromodeoxyuridine（Brd U）＋, nestin＋,T-box transcription factor 2（Tbr2）＋, Brd U＋/doublecortin（DCX）＋, Brd U＋/ionized calcium-binding adaptor molecule 1（Iba1）＋, and Brd U＋/neuronal nuclei（Neu N）＋ cells in the hippocampus were increased in the Ta1 group,accompanied by increased interleukin-4（IL-4）, interferon-gamma, brain-derived neurotrophic factor, nerve growth factor, and insulin-like growth factor-1 as well as decreased IL-6 and tumor necrosis factor-a. Furthermore, the Ta1-group showed a Th1-polarized immune response, and the neurotrophic factors were positively associated with the Th1/Th2 ratio. More importantly, administration of Ta1 blocked lipopolysaccharide-induced impairment of hippocampal neurogenesis in early life. These findings suggest that peripheral Ta1 contributes to neurogenesis and cognition probably through a systemic Th1 bias, as well as neuroprotection against LPS infection by Ta1.

关键词： Microglia Th1/Th2 bias IGF-1 Brain-derived neurotrophic factor Nerve growth factor

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Thymosin Alpha-1 Inhibits Complete Freund’s Adjuvant-Induced Pain and Production of Microglia-Mediated Pro-inflammatory Cytokines in Spinal Cord

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Neuroscience Bulletin 2019年第4期35卷 637-648页

作者： Yunlong Xu Yanjun Jiang Lin Wang Jiahua Huang Junmao Wen Hang Lv Xiaoli Wu Chaofan Wan Chuanxin Yu Wenjie Zhang Jiaying Zhao Yinqi Zhou Yongjun Chen South China Research Center for acupuncture and moxibustion Medical College of Acu-Moxi and Rehabilitation Guangzhou University of Chinese Medicine Guangzhou 510006 China college of Basic medical Science Guangzhou University of Chinese Medicine Guangzhou 510006 China The First Clinical college of Guangzhou University of Chinese Medicine Guangzhou 510006 China Graduate college Guangzhou University of Chinese Medicine Guangzhou 510006 China

Activation of inflammatory responses regulates the transmission of pain pathways through an integrated network in the peripheral and central nervous *** immunopotentiator thymosin alpha-1(Tal)has recently been reported to have anti-inflammatory and neuroprotective functions in ***,how Tα1 affects inflammatory pain remains *** the present study,intraperitoneal injection of Tal attenuated complete Freund's adjuvant(CFA)-induced pain hypersensitivity,and decreased the up-regulation of pro-inflammatory cytokines(TNF-α,IL-1β,and IL-6)in inflamed skin and the spinal *** found that CFA-induced peripheral inflammation evoked strong microglial activation,but the effect was reversed by Tα***,Tα1 reversed the CFA-induced up-regulation of vesicular glutamate transporter(VGLUT)and down-regulated the vesicular γ-aminobutyric acid transporter(VGAT)in the spinal *** together,these results suggest that Tα1 plays a therapeutic role in inflammatory pain and in the modulation of microgliainduced pro-inflammatory cytokine production in addition to mediation of VGLUT and VGAT expression in the spinal cord.

关键词： Thymosin alpha-1 Cytokine Microglia Vesicular glutamate transporter type 2 Vesicular γ-aminobutyric acid transporter

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