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Targeting ASIC1a promotes Neural progenitor Cell Migration and Neurogenesis in Ischemic Stroke

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Research 2024年第1期2023卷 369-387页

作者： Hongfei Ge Tengyuan Zhou Chao Zhang Yupeng Cun Weixiang Chen Yang Yang Qian Zhang Huanhuan Li Jun Zhong Xuyang Zhang Hua Feng Rong Hu department of Neurosurgery and Key Laboratory of Neurotrauma Southwest HospitalThird Military Medical University(Army Medical University)400038 ChongqingChina medical Research Center Southwest HospitalThird Military Medical University(Army Medical University)400038 ChongqingChina pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChildren’s Hospital of Chongqing Medical University400014 ChongqingChina

Cell replacement therapy using neural progenitor cells(Npcs)has been shown to be an effective treatment for ischemic ***,the therapeutic effect is unsatisfactory due to the imbalanced homeostasis of the local microenvironment after *** acidosis is a common imbalanced homeostasis in the penumbra and could activate acid-sensing ion channels 1a(ASIC1a),a subunit of proton-gated cation channels following ischemic ***,the role of ASIC1a in Npcs post-ischemia remains ***,our results indicated that ASIC1a was expressed in Npcs with channel functionality,which could be activated by extracellular *** evidence revealed that ASIC1a activation inhibited NpC migration and neurogenesis through RhoA signaling-mediated reorganization of filopodia formation,which could be primarily reversed by pharmacological or genetic disruption of *** vivo data showed that the knockout of the ASIC1a gene facilitated NpC migration and neurogenesis in the penumbra to improve behavioral recovery after stroke.

关键词： ASIC1a homeostasis inhibited

Vitamin A deficiency suppresses CEACAM1 to impair colonic epithelial barrier function via downregulating microbial-derived short-chain fatty acids

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Genes & Diseases 2024年第2期11卷 1066-1081页

作者： Junyan Yan Lu Xiao Di Feng Baolin Chen Ting Yang Bei Tong Ruifang Luo Yuting Wang Jie Chen children Nutrition Research Center Children's Hospital of Chongqing Medical UniversityChongqing Key Laboratory of Child Nutrition and HealthMinistry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing 401122China department of Gastroenterology Children's Hospital of Chongqing Medical UniversityChongqing 401122China

Vitamin A (VA) plays an essential role in modulating both the gut microbiota and gut barrier ***-chain fatty acids (SCFAs),as metabolites of the gut microbiota,protect the physiological intestinal barrier;however,they are compromised when VA is ***,there is an urgent need to understand how and which SCFAs modulate colonic epithelial barrier integrity in VA deficiency (VAD).Herein,compared with normal VA rats (VAN),at the beginning of pregnancy,we confirmed that the colonic desmosome junction was impaired in the VAD group,and the amounts of acetate,propionate,and butyrate declined because of the decreased abundance of SCFA-producing bacteria (Romboutsia ,Collinsella ,and Allobaculum ).The differentially expressed genes correlated with the gut barrier and the histone deacetylase complex between the VAD and VAN groups were enriched by RNA *** the VAD group,the expression levels of colonic CEA cell adhesion molecule 1 (CEACAM1) were down-regulated,and the levels of histone deacetylase 1 (HDAC1) and HDAC3 were ***,the above changes in the VAD groups were rescued by VA supplementation in the early postnatal *** study indicated that in Caco-2 cells,butyrate treatment significantly repressed the enrichment of HDAC3 on the promoter of the CEACAM1 gene to induce its *** findings support that butyrate intervention can alleviate the impairment of colonic barrier function caused by VAD,and timely postnatal VA intervention may reverse the damage caused by VAD on gut barrier integrity during pregnancy.

关键词： CEACAM1 Colonic epithelial barrier HDAC3 Short-chain fatty acids Vitamin A deficiency

Recent advancement of sonogenetics:A promising noninvasive cellular manipulation by ultrasound

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Genes & Diseases 2024年第5期11卷 163-182页

作者： Jin Tang Mingxuan Feng Dong Wang Liang Zhang Ke Yang pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Engineering Research Center of Stem Cell TherapyChongqing 400014China department of Ultrasound The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Tongji medical College Huazhong University of Science and TechnologyWuhanHubei 430074China

Recent advancements in biomedical research have underscored the importance of noninvasive cellular manipulation ***,a method that uses genetic engineering to produce ultrasound-sensitive proteins in target cells,is gaining prominence along with optogenetics,electrogenetics,and *** stimulation with ultrasound,these proteins trigger a cascade of cellular activities and *** traditional ultrasound modalities,sonogenetics offers enhanced spatial selectivity,improving precision and safety in disease *** technology broadens the scope of non-surgical interventions across a wide range of clinical research and therapeutic applications,including neuromodulation,oncologic treatments,stem cell therapy,and *** current literature predominantly emphasizes ultrasonic neuromodulation,this review offers a comprehensive exploration of *** discuss ultrasound properties,the specific ultrasound-sensitive proteins employed in sonogenetics,and the technique’s potential in managing conditions such as neurological disorders,cancer,and ophthalmic diseases,and in stem cell *** objective is to stimulate fresh perspectives for further research in this promising field.

关键词： Mechanosensitive channel Neuromodulation Sonogenetics Ultrasound Ultrasound-sensitive protein

postoperativeinte rictalepil eptiform discharges predict seizure recurrence after antiepileptic drug withdrawal regardless of concordance with surgical site

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World Journal of pediatric Surgery 2024年第1期7卷 33-41页

作者： Yuxin Wu ZaiYu Zhang ping Liang Lusheng Li Bin Zou Difei Wang Xinyu Dong Haotian Tang Hanli Qiu Xuan Zhai department of Neurosurgery Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqingChina

Objective The study aimed to explore the association between the site of interictal epileptic discharges(IEDs)on postoperative electroencephalogram(EEG)and seizure recurrence after antiepileptic drug(AED)*** study hypothesizes that the concordance of IED sites with surgical sites indicates incomplete resection of epileptic focus,while non-concordance of IED sites with surgical sites indicates postoperative changes or cortical *** former has a higher risk of seizure *** We retrospectively analyzed the postoperative EEG pattern of 182 consecutive children who underwent resection *** identify the risk factors for seizure recurrence,we compared the attributes of seizure recurred and seizure-free groups by univariate and multivariate *** tapering was standardized,involving a 25% reduction in the dose of a single type of AED every 2 weeks,independent of the presurgical AED *** We attempted AED withdrawal in 116(63.7%)***-eight(24.1%)children experienced seizure recurrence during or after AED withdrawal.A greater number of AEDs used at the time of surgery(p=0.005),incomplete resection(p=0.001),and presence of IED on postoperative EEG(p=0.011)are predictors of *** resectionand seizure recurrence after AED withdrawal were related to the presence of IED on the EEG,but not to the concordance of IED with surgical *** For children with abnormal EEG,the decision to discontinue AED should be made more cautiously,regardless of the relative location of the discharge site and the surgical site.

关键词： surgical seizure epileptic

A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort

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Genes & Diseases 2024年第4期11卷 400-410页

作者： Han Chan Fenfen Ni Bo Zhao Huimin Jiang Juanjuan Ding Li Wang Xiaowen Wang Jingjing Cui Shipin Feng Xiaojie Gao Xueying Yang Huan Chi Hao Lee Xuelan Chen Xiaoqin Li Jia Jiao Daoqi Wu Gaofu Zhang Mo Wang Yupeng Cun Xiongzhong Ruan Haiping Yang Qiu Li department of Nephrology Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqing 400014China department of Nephrology Shenzhen Children's HospitalShenzhenGuangdong 518034China department of Nephrology Kunming Children's HospitalKunming Medical UniversityKunmingYunnan 650228China department of Nephrology Wuhan Children's HospitalTongji Medical College of Huazhong University of Science and TechnologyWuhanHubei 430015China department of Nephrology Chengdu Women and Children Central HospitalChengduSichuan 610073China pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China department of Nephrology John Moorhead Research LaboratoryUniversity College London Medical SchoolRoyal Free CampusUniversity College LondonLondon NW32PFUnited Kingdom

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(GWAS)strategy is important for understanding the *** conducted a multicenter cohort study(360 patients and 1835 controls)combined with a GWAS strategy to identify susceptibility var-iants associated with the following two subphenotypes of ssNS:steroid-sensitive nephrotic syn-drome without relapse(SSNswR,181 patients)and steroid-dependent/frequent relapse nephrotic syndrome(SDNS/FRNS,179 patients).The distribution of two single-nucleotide poly-morphisms(SNps)in ANKRD36 and ALpG was significant between SSNSWR and healthy controls,and that of two SNps in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy ***,rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for *** significant SNps were observed between SSNSWR and SDNS/***,chromosome 2:171713702 in GAD1 was associated with a greater steroid dose(>0.75 mg/kg/d)upon relapse to first remission in patients with SDNS/FRNS(odds ratio=3.14;95%confidence interval,0.97-9.87;p=0.034).rs117014418 in ApOL4 was significantly associated with a decrease in eGFR of greater than 20%compared with the baseline in SDNS/FRNS patients(p=0.0001).protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through ***,SSNSWR belongs to non-HLA region-dependent nephropathy,and the HLA-DQA/DQB region is likely strongly associated with dis-ease relapse,especially in SDNS/*** study provides a novel approach for the GWAS strategy of SsNS and contributes to our understanding of the pathological mechanisms of SSNSWRandSDNS/FRNS.

关键词： Frequentrelapse Genome-wide association study Human leukocyte antigen region Steroid-sensitive nephrotic syndrome

Resident immune responses to spinal cord injury:role of astrocytes and microglia

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Neural Regeneration Research 2024年第8期19卷 1678-1685页

作者： Sydney Brockie Cindy Zhou Michael G.Fehlings Division of genetics and development Krembil Research InstituteUniversity Health NetworkTorontoONCanada Institute of medical Science University of TorontoTorontoONCanada Division of Neurosurgery and Spine program Department of SurgeryUniversity of TorontoTorontoONCanada

Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our *** r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal *** makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative *** these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory *** review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after ***,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural *** the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous *** advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are *** key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

关键词： astrocytes glial signaling microglia spinal cord injury synaptic transmission

Current understanding of ELF4 deficiency:a novel inborn error of immunity

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World Journal of pediatrics 2024年第5期20卷 444-450页

作者： Hong-Qiang Du Xiao-Dong Zhao department of Rheumatology&Immunology National Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of Child Rare Diseases in Infection and ImmunityChildren’s Hospital of Chongqing Medical UniversityZhongshan Er Road 136Yuzhong DistrictChongqingChina

Background ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity(IEIs),specifically categorized as a“disease of immune dysregulation.”Cases of this condition,reported by our team and others,are very limited *** such,our current knowledge of this new disease remains *** review aims to provide a brief overview of the clinical manifestations,pathogenesis,and treatment strategies for this novel *** sources A comprehensive review was conducted after an extensive literature search in the pubMed/Medline database and websites concerning transcriptional factor ELF4 and reports concerning patients with ELF4 *** search strategy was“ELF4 OR ETS-related transcription factor Elf-4 OR EL4-like factor 4 OR myeloid Elf-1-like factor”as of the time of manuscript *** The current signature manifestations of ELF4 deficiency disorder are recurrent and prolonged oral ulcer,abdominal pain,and diarrhea in pediatric *** some cases,immunodeficiency and autoimmunity can also be *** Sanger sequencing or whole exome sequencing can be used to detect variation in ELF4 *** blotting for ELF4 expression of the patient’s cells can confirm the pathogenic effect of the *** fully confirm the pathogenicity of the variant,further functional test is strongly *** and biologics are the mainstream management of ELF4 deficiency *** pediatric males presenting with recurring ulcerations in digestive tract epithelium with or without recurrent fever should be suspected of *** atypical presentations are prominent,variations in ELF4 gene should be carefully evaluated functionally due to the complex nature of ELF4 *** of treating DEX includes use of glucocorticoid and biologics and more precise treatment needs more patients to identify and further mechanistic study.

关键词： ELF4 transcription factor Immune dysregulation Inborn errors of immunity Mechanism Recurrent infections

X-box binding protein 1 caused an imbalance in pyroptosis and mitophagy in immature rats with di-(2-ethylhexyl)phthalate-induced testis toxicity

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Genes & Diseases 2024年第2期11卷 935-951页

作者： Yifan Hong Xiazhu Zhou Qi Li Jing Chen Yuexin Wei Chunlan Long Lianju Shen Xiangqin Zheng Dinggang Li Xia Wang Chenjun Yu Shengde Wu Guanghui Wei department of Urology Children's Hospital of Chongqing Medical UniversityChongqing 400014China pediatric Research Institute Children's Hospital of Chongqing Medical UniversityChongqing 400014China Chongqing Key Laboratory of children Urogenital development and Tissue Engineering Children's Hospital of Chongqing Medical UniversityChongqing 400014China Chongqing Key Laboratory of pediatrics Children's Hospital of Chongqing Medical UniversityChongqing 400014China Ministry of Education Key Laboratory of child development and Disorders Children's Hospital of Chongqing Medical UniversityChongqing 400014China National Clinical Research Center for child Health and Disorders Children's Hospital of Chongqing Medical UniversityChongqing 400014China China International Science and Technology Cooperation Base of child development and Critical Disorders Children's Hospital of Chongqing Medical UniversityChongqing 400014China

As a widely used plasticizer,di-(2-ethylhexyl)phthalate(DEHp)is known to induce significant testicular ***,the potential mechanism and effects of pubertal exposure to DEHp on testis development remain *** vivo,postnatal day(pND)21 male rats were gavaged with 0,250,and 500 mg/kg DEHp for ten *** to the seminiferous epithelium and disturbed spermatogenesis were observed after DEHp ***,oxidative stress-induced injury and pyroptosis were *** endoplasmic reticulum(ER)stress and mitophagy were involved in this *** phthalate(MEHp)was used as the biometabolite of DEHp in *** GC-1 and GC-2 cell lines were exposed to 0,100μM,200μM,and 400μM MEHp for 24 *** oxygen species(ROS)generation,oxidative stress damage,ER stress,mitophagy,and pyroptosis were significantly increased after MEHp *** ultrastructure of the ER and mitochondria was destroyed.X-box binding protein 1(XBp1)was observed to be activated and translocated into the *** generation was inhibited by *** levels of antioxidative stress,ER stress,mitophagy,and pyroptosis were decreased as *** the administration of the ER stress inhibitor 4-phenyl-butyric acid,both mitophagy and pyroptosis were ***-induced XBp1 down-regulation decreased the levels of mitophagy and *** equilibrium between pyroptosis and mitophagy was disturbed by XBp1 *** summary,our findings confirmed that DEHp induced a ROS-mediated imbalance in pyroptosis and mitophagy in immature rat testes via ***,XBp1 might be the key target in DEHp-related testis dysfunction.

关键词： DEHp Mitophagy pyroptosis Testicular development XBp1

How aging affects bone health via the intestinal micro-environment

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BIOCELL 2024年第3期48卷 353-362页

作者： HUAN HU YUE HUANG FANGZHOU LIU QIAN WANG YANZI YAO School of Stomatology Zunyi Medical UniversityZunyiChina Microbial Resources and Drug development Key Laboratory of Guizhou Tertiary Institution Zunyi Medical UniversityZunyiChina department of Stomatology Luoyang Maternal and Child Health HospitalLuoyangChina

Increasing life expectancy and an aging population lead to age-related bone diseases like osteoporosis and low bone mass more *** conditions represent a common,costly and chronic burden,not only for elderly but also to society at ***,elucidating the pathophysiology and developing effective therapies for these diseases is of paramount *** advances in research have identiﬁed the gut as a novel and promising target for addressing bone disorders,giving rise to the concept of the“gut-bone axis”.An in-depth review of the latest insights into the effects of age-related physiological changes in the gastrointestinal tract on bone health is presented in this *** examines how the“gut-bone”axis interacts with bone aging across various domains,including metabolism,nutrition,intestinal permeability,immunity,and oxidative stress.

关键词： Gut barrier Skeletal system Senescent Gut-bone axis Gut microbiota