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C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

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Neural Regeneration Research 2025年第8期20卷 2231-2244页

作者： Xiangzi Wang Xiaofei Niu Yingkai Wang Yang Liu Cheng Yang Xuyi Chen Zhongquan Qi School of Medicine Guangxi UniversityNanningGuangxi Zhuang Autonomous RegionChina Graduate School of Tianjin University of Traditional Chinese Medicine TianjinChina Characteristic Medical center of People’s Armed Police Forces TianjinChina Fujian Maternity and child health Hospital FuzhouFujian ProvinceChina

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory *** expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after *** studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for *** review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord ***,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 *** review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted ***,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 *** review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.

关键词： apoptosis C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway C-C motif chemokine receptor 2 antagonists chemokine ligand 2 chemokine receptor 2 inflammation macrophage microglia spinal cord injury therapeutic method

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Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

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Neural Regeneration Research 2025年第1期20卷 265-276页

作者： Yao Yuan Lingqi Yu Xudong Zhuang Dongjing Wen Jin He Jingmei Hong Jiayu Xie Shengan Ling Xiaoyue Du Wenfeng Chen Xinrui Wang Institute of Life Sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouFujian ProvinceChina NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate(Fujian Maternity and child health Hospital) FuzhouFujian ProvinceChina Medical Research center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology and Institute of Neurology of The First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory *** develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause *** located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)*** addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive *** these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut *** found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in *** heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal *** Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

关键词： ATP1A1 Atpα bang-sensitive paralysis Charcot-Marie-Tooth disease type 2 CRISPR/Cas9 homology-directed repair Na^(+)/K^(+)-ATPase point mutation seizures sodium pump

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Peficitinib suppresses diffuse-type tenosynovial giant cell tumor by targeting TYK2 and JAK/STAT signaling

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Science China Life Sciences 2025年

作者： Shan Lu Chenxi Cao Wenjia Zhang Jiayi Li Jingli Yang Zisheng Huang Zhijun Wu Baitao Liu Hongjie Huang Haijun Wang Yongjian Wang Dingge Liu Zhihua Zhang Kaiping Liu Gang Yang Xi Gong Hui Dai Yingjia Li Erdan Dong Xin Zhang Yan Zhang Haihe Laboratory of Cell Ecosystem Institute of Cardiovascular Diseases The First Affiliated Hospital of Dalian Medical University Institute of Cardiovascular Sciences School of Basic Medical Sciences Peking University Health Science Center Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalState Key Laboratory of Vascular Homeostasis and Remodeling Peking University Department of sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University Beijing Key Laboratory of sports Injuries Engineering Research center of sports Trauma Treatment Technology and Devices Ministry of Education State Key Laboratory of Membrane Biology Institute of Molecular Medicine College of Future Technology Peking University Peking University health Science Centre Peking University Department of Immunology School of Basic Medical Sciences NHC Key Laboratory of Medical Immunology Peking University Research center for Cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital) School of Health and Life Sciences University of Health and Rehabilitation Sciences Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases Chinese Academy of Medical Sciences

Diffuse-type tenosynovial giant cell tumor(dTGCT) is a destructive but rare benign proliferative synovial neoplasm. Although surgery is currently the main treatment modality for dTGCT, the recurrence risk is up to 50%. Therefore, there is a great need for effective drugs against dTGCT with minor side effects. The Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling plays a central role in rheumatoid arthritis(RA), a disease with similar characteristics as dTGCT, but its function in dTGCT remains *** fibroblast-like synoviocytes(FLS) and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT. Cell viability, cell death, inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D) and macrophages were investigated for the efficacy of the JAK inhibitors. Here, we found that similar to RA, JAK/STAT signaling was markedly activated in the dTGCT synovium. Of the 5 JAK inhibitors, peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and *** potency of peficitinib was much higher than pexidartinib, which is the only FDA-approved drug for dTGCT. Mechanistically, peficitinib inhibited tyrosine kinase 2(TYK2), a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages. In summary, we not only revealed JAK/STAT(especially TYK2) signaling as the major mechanism underlying dTGCT, but also identified peficitinib as a promising drug against dTGCT.

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Dissecting the cell microenvironment of ovarian endometrioma through single-cell RNA sequencing

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Science China Life Sciences 2025年第1期68卷 116-129页

作者： Jiangpeng Wu Siyu Xia Wenting Ye Yan Sun Jing Cai Fubing Yu Haiping Wen Xiuwei Yi Taikang Li Mingwei Chen Jiayun Chen Ge Song Chuanbin Yang Yali Song Jigang Wang Department of Reproductive Medicine Dongguan Maternal and Child Health Care Hospital Department of Urology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalSouthern University of Science and Technology State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical Sciences Reproductive Medicine center Foshan Women and Children Hospital State Key Laboratory of Antiviral Drugs School of PharmacyHenan University

Ovarian endometrioma（OE）, also known as “chocolate cysts,” is a cystic mass that develops in the ovaries due to endometriosis and is a common gynecological condition characterized by the growth of endometrial tissue outside the uterus, leading to symptoms such as dysmenorrhea, pelvic pain, and infertility. However, the precise molecular and cellular mechanisms driving this pathophysiology remain largely unknown, posing challenges for diagnosis and treatment. Here, we employed integrated single-cell transcriptomic profiling of over 52,000 individual cells from endometrial tissues of OE patients and healthy donors and identified twelve major cell populations. We identified notable alterations in cell type-specific proportions and molecular signatures associated with OE. Notably, the activation of IGFBP5+macrophages with pro-inflammatory properties, NK cell exhaustion, and aberrant proliferation of IQCG+and KLF2+epithelium are key features and may be the potential mechanisms underlying the pathogenesis of OE. Collectively, our data contribute to a better understanding of OE at the single cell level and may pave the way for the development of novel therapeutic strategies.

关键词： ovary high-throughput sequencing transcriptomics gene expression analysis ligand-receptor analysis

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Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

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Neural Regeneration Research 2025年第9期20卷 2633-2644页

作者： Zhimin Long Chuanhua Ge Yueyang Zhao Yuanjie Liu Qinghua Zeng Qing Tang Zhifang Dong Guiqiong He Institute of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqingChina Department of Anatomy Chongqing Medical UniversityChongqingChina Department of Physiology Chongqing Medical UniversityChongqingChina Pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityChongqingChina Ministry of Education Key Laboratory of child Development and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina National Clinical Research center for child health and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of child Neurodevelopment and Cognitive Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque ***,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's *** acetylation/deacetylation plays a central role in lysosomal ***,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's *** rthermore,we found that treatment with valproic acid markedly enhanced *** clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's *** findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

关键词： Alzheimer's disease amyloid-β APP/PS1 mice autophagy cognitive impairment histone deacetylase 6 lysosomal acidification microtubule acetylation valproic acid V-ATPase

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A dry-electrode enabled ECG-on-Chip with arrhythmia-aware data transmission

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Science China(Information Sciences) 2025年

作者： Xinzi XU Yanxing SUO Yang ZHAO Peiyi ZHOU Xiao HAN Qiao CAI Min WANG Jiajun YUAN Liebin ZHAO Yongfu LI Guoxing WANG Yong LIAN Department of Micro-Nano Electronics and MoE Key Lab of Artificial Intelligence Shanghai Jiao Tong University Pediatric AI Clinical Application and Research center Shanghai Engineering Research Center of Intelligence Pediatrics (SERCIP) Child Health Advocacy Institute Shanghai Children's Medical Center School of MedicineShanghai Jiao Tong University Shanghai Engineering Research center of Intelligence Pediatrics (SERCIP) Xin Hua Hospital Affiliate to Shanghai Jiao Tong University School of Medicine

Early detection and treatment of cardiovascular diseases (CVDs) can be significantly enhanced through the use of flexible wearable electrocardiogram (ECG) sensors, potentially reducing CVD-related mortality. This paper introduces an ECG-on-Chip (EoC) solution tailored for flexible ECG sensors, incorporating novel features to address common challenges in wearable ECG technology. The EoC integrates a chopper-stabilized capacitively-coupled instrumentation amplifier (CS-CCIA),ensuring a high common-mode rejection ratio (CMRR) and low noise performance. Performance is further boosted via a positive feedback loop (PFL) and a programmable gain amplifier (PGA) with shared on-chip calibration logic, which enhances input impedance and minimizes gain variability to ensure consistent algorithm performance. Additionally, a secondary chopping technique is employed to further reduce noise, achieving an input-referred noise level of 454 nVrms. The embedded algorithm within the EoC is designed to extract clinically meaningful features, facilitating robust real-time arrhythmia analysis. Fabricated using a 0.18μm CMOS process, the EoC consumes 14.9μW with a supply voltage of 1.2 V. The algorithm’s efficacy has been validated over 0.4 million heartbeats, demonstrating a sensitivity of over 99.7%for R-peak detection and 98.3%for arrhythmia analysis. To demonstrate practical application, the EoC has been integrated with a commercial Bluetooth low energy (BLE)transceiver, forming a wireless arrhythmia monitoring sensor equipped with dry electrodes. This system consumes 292.04μW in arrhythmia-aware transmission mode, supporting 13 days of operation with a 30 mAh thin-film battery.

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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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Advances in the treatment of autism spectrum disorder:Wharton jelly mesenchymal stem cell transplantation

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World Journal of Methodology 2025年第1期15卷 72-79页

作者： Serdar Kabatas ErdinçCivelek Eyüp Can Savrunlu Umut Karaaslan Özlem Yıldız Erdal Karaöz Department of Neurosurgery University of Health Sciences TurkeyGaziosmanpaşa Training and Research HospitalIstanbul 34255Türkiye Department of Pediatric Allergy-Immunology Institute of Health Sciences Marmara UniversityIstanbul 34865Türkiye center for Stem Cell&Gene Therapy Research and Practice University of Health Sciences TurkeyIstanbul 34255Türkiye Department of child and Adolescent Psychiatry University of Health SciencesGaziosmanpaşa Training and Research HospitalIstanbul 34255Türkiye Department of child and Adolescent Psychiatry Kocaeli University Faculty of MedicineKocaeli 41001Türkiye center for Regenerative Medicine and Stem Cell Research&Manufacturing Liv HospitalIstanbul 34340Türkiye Department of Histology and Embryology Istinye UniversityFaculty of MedicineIstanbul 34010Türkiye center for Stem Cell and Tissue Engineering Research and Practice Istinye UniversityIstanbul 34340Türkiye

BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted *** recent studies,neuroinflammation and immune dysregulation have come to the forefront in its *** are studies suggesting that stem cell therapy may be effective in the treatment of *** To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell *** A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with *** The study demonstrates a significant improvement in the child’s functional outcomes(childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor *** serious side effects were encountered during the 2-year *** The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.

关键词： Autism spectrum disorder Neurorehabilitation Stem cell transplantation Wharton jelly mesenchymal stem cells Inflammation

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Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1749-1763页

作者： Tian Qin Yuxin Jin Yiming Qin Feifei Yuan Hongbin Lu Jianzhong Hu Yong Cao Chengjun Li Department of Spine Surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National Clinical Research center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of sports Medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关键词： corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury syringin TRIB2

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Secular Changes on the Distribution of Body Mass Index among Chinese children and Adolescents, 1985-2010

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Biomedical and Environmental Sciences 2013年第7期26卷 520-530页

作者： JI Cheng Ye CHEN Tian Jiao SUN Xiao Institute of child and Adolescent health School of Public Health Peking University Health Science Center

Objective To analyze the change in Body Mass Index （BMI） distribution among Chinese children and adolescents for the development of more effective intervention for childhood obesity. Methods Data on the national students＇ constitution and health survey between 1985 and 2010 was used for this study. Subjects were students aged 7-18 randomly selected from 30 provinces in China. BMI for-age curves were developed by LMS method, and the trend of BMI distribution was determined by comparing the upper BMI percentiles and analyzing the skew shift of distribution between 2985 and 2010. Results An overall positive swift trend of BMI between 1985 and 2010 was observed among the Chinese school-age children and adolescents. The average median of the BMI increased from 16.8 and 17.0 ks/m2 to 18.2 and 17.9 kg/m2 in 25 years, with increments 0.56 and 0.36 kg/m2 per decade for males and females, respectively. The more obvious increments were found at the high BMI. The total increments of BMI in this period were 4.03 and 2.20 kg/m2 at the 85th, 6.24 and 3.57 kg/m2 at the 95th, and 6.99 and 4.27 kg/m2 at the 97th percentiles, for males and females, respectively. Conclusion Obvious increments were observed at high BMI of the Chinese children and adolescents. More effective interventions should be taken for control and prevention of obesity and its health consequence for these subgroups. It is necessary to establish a risk-complex system consisting of the identification of BMI scope, the screen of the disease risk factors and the assessment of excessive adiposity.

关键词： Body mass index Obesity Chinese School-age children Secular growth changes

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