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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

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

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

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

The roles of RACK1 in the pathogenesis of Alzheimer's disease

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Journal of Biomedical Research 2024年第2期38卷 137-148页

作者： Wenting He Xiuyu Shi Zhifang Dong Pediatric Research Institute Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing Key Laboratory of Child Neurodevelopment and Cognitive DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China

The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative ***1 is highly expressed in neuronal cells of the central nervous system and regulates the pathogenesis of ***,RACK1 is involved in regulation of the amyloid-β precursor protein processing through α-or β-secretase by binding to different protein kinase C ***,RACK1 promotes synaptogenesis and synaptic plasticity by inhibiting N-methyl-D-aspartate receptors and activating gamma-aminobutyric acid A receptors,thereby preventing neuronal ***1 also assembles inflammasomes that are involved in various neuroinflammatory pathways,such as nuclear factor-kappa B,tumor necrosis factor-alpha,and NOD-like receptor family pyrin domain-containing 3 *** potential to design therapeutics that block amyloid-β accumulation and inflammation or precisely regulate synaptic plasticity represents an attractive therapeutic strategy,in which RACK1 is a potential *** this review,we summarize the contribution of RACK1 to the pathogenesis of AD and its potential as a therapeutic target.

关键词： RACK1 Alzheimer's disease PKC amyloid-β synaptic plasticity neuroinflammation

development and validation of a novel non-invasive test for diagnosing nonalcoholic fatty liver disease in Chinese children

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World Journal of Pediatrics 2024年第4期20卷 413-421页

作者： Zhe-Wen Qin Qian-Nan Ren Hong-Xi Zhang Ya-Ru Liu Ke Huang Wei Wu Guan-Ping Dong Yan Ni Jun-Fen Fu Division of Endocrinology National Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalDepartment of EndocrinologyNational Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalZhejiang University School of MedicineHangzhou310052China

With the exploding prevalence of obesity,many children are at risk of developing nonalcoholic fatty liver *** anthropometric and laboratory parameters,our study aimed to develop a model to quantitatively evaluate liver fat content(LFC)in children with *** A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the Endocrinology Department as the derivation *** external validation cohort comprised 77 *** assessment of liver fat content was performed using proton magnetic resonance *** and laboratory metrics were measured in all subjects.B-ultrasound examination was carried out in the external validation *** Kruskal-Wallis test,Spearman bivariate correlation analyses,univariable linear regressions and multivariable linear regression were used to build the optimal predictive *** The model was based on indicators including alanine aminotransferase,homeostasis model assessment of insulin resistance,triglycerides,waist circumference and Tanner *** adjusted R^(2)of the model was 0.589,which presented high sensitivity and specificity both in internal[sensitivity of 0.824,specificity of 0.900,area under curve(AUC)of 0.900 with a 95%confidence interval:0.783–1.000]and external validation(sensitivity of 0.918 and specificity of 0.821,AUC of 0.901 with a 95%confidence interval:0.818–0.984).Conclusions Our model based on five clinical indicators was simple,non-invasive,and inexpensive;it had high sensitivity and specificity in predicting LFC in ***,it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.

关键词： Biochemical markers children Magnetic resonance spectroscopy Nonalcoholic fatty liver disease Pediatric obesity

Aberrant LETM1 elevation dysregulates mitochondrial functions and energy metabolism and promotes lung metastasis in osteosarcoma

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Genes & Diseases 2024年第3期11卷 368-384页

作者： Yulu Shi Quan Kang Hong Zhou Xiaohan Yue Yang Bi Qing Luo Stem Cell Biology and Therapy Laboratory The 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 Pediatric Surgery The Children's Hospital of Chongqing Medical UniversityChongqing 400014China

Osteosarcoma is a differentiation-deficient disease,and despite the unique advan-tages and great potential of differentiation therapy,there are only a few known differentia-tion inducers,and little research has been done on their *** differentiation is associated with an increase in mitochondrial content and *** metabolism of some tu-mor cells is characterized by impaired oxidative phosphorylation,as well as up-regulation of aerobic glycolysis and pentose phosphate ***-containing zipper and EF-hand transmembrane protein 1(LETM1)is involved in the maintenance of mitochondrial morphology and is closely associated with tumorigenesis and progression,as well as cancer cell *** found that MG63 and 143B osteosarcoma cells overexpress LETM1 and exhibit abnormalities in mitochondrial structure and *** of LETM1 partially restored the mitochon-drial structure and function,inhibited the pentose phosphate pathway,promoted oxidative phosphorylation,and led to osteogenic *** also inhibited spheroid cell forma-tion,proliferation,migration,and invasion in an in vitro *** LETM1 was knocked down in vivo,there was reduced tumor formation and lung *** data suggest that mitochondria are aberrant in LETM1-overexpressing osteosarcoma cells,and knockdown of LETM1 partially restores the mitochondrial structure and function,inhibits the pentose phosphate pathway,promotes oxidative phosphorylation,and increases osteogenic differentiation,thereby reducing malignant biological behavior of the cells.

关键词： Cancer metabolism Differentiation LETM1 Osteosarcoma Stemness

Ultrasonic manifestations and age distribution of internal abdominal hernia in children

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中国医学影像技术 2024年第8期40卷 1204-1207页

作者： KUANG Bin YANG Chunjiang TANG Yi Department of Ultrasound 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 Pediatric Metabolism and Inflammatory DiseasesChongqing 400014China

Objective To observe the ultrasonic manifestations and age distribution of internal abdominal hernia in *** Data of 53 children with internal abdominal hernia confirmed by operation were retrospectively *** ultrasonic findings were observed,and the age distribution of children was *** Among 53 cases,"cross sign"was observed in 22 cases(22/53,41.51%),and"hernia ring beak sign"was detected in 26 cases(26/53,49.06%)by preoperative ultrasound,according to which 21 cases were diagnosed as internal abdominal hernia,with the accuracy of 39.62%(21/53).Meanwhile,manifestations of intestinal obstruction were noticed in 48 cases(48/53,90.57%),and intestinal necrosis was considered in 22 cases(22/53,41.51%).Four cases were misdiagnosed as intestinal perforation,appendicitis,intestinal atresia and volvulus,each in 1 *** onset age of postoperative adhesive band internal hernia was larger than that of mesenteric hiatal hernia(P0.05).Intestinal ischemic necrosis was found in 25 cases,while the incidence of intestinal necrosis in children aged≤1 year,>1 and≤3 years,>3 and≤7 years and those>7 years was 66.67%(12/18),33.33%(4/12),36.36%(4/11)and 41.67%(5/12),*** The characteristic ultrasonic findings of internal abdominal hernia in children included"cross sign"and"hernia ring beak sign".Internal abdominal hernia in children under 1 year had high risk of intestinal necrosis.

关键词： hernia,abdominal children ultrasonography