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Diabetic cardiomyopathy:Importance of direct evidence to support the roles of NOD-like receptor protein 3 inflammasome and pyroptosis

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World Journal of diabetes 2024年第8期15卷 1659-1662页

作者： Lu Cai Yi Tan Md Shahidul Islam Michael Horowitz Kupper A Wintergerst pediatric research Institute Departments of PediatricsRadiation OncologyPharmacology and ToxicologyUniversity of LouisvilleWendy Novak Diabetes InstituteNorton Children’s HospitalLouisvilleKY 40202United States department of Biochemistry School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa department of Medicine University of AdelaideAdelaide 5005Australia pediatric research Institute Division of EndocrinologyDepartment of PediatricsWendy Novak Diabetes InstituteNorton Children’s HospitalUniversity of LouisvilleLouisvilleKY 40202United States

Recently,the roles of pyroptosis,a form of cell death induced by activated NODlike receptor protein 3(NLRP3)inflammasome,in the pathogenesis of diabetic cardiomyopathy(DCM)have been extensively ***,most studies have focused mainly on whether diabetes increases the NLRP3 inflammasome and associated pyroptosis in the heart of type 1 or type 2 diabetic rodent models,and whether various medications and natural products prevent the development of DCM,associated with decreased levels of cardiac NLRP3 inflammasome and *** direct link of NLRP3 inflammasome and associated pyroptosis to the pathogenesis of DCM remains unclear based on the limited evidence derived from the available studies,with the approaches of NLRP3 gene silencing or pharmaceutical application of NLRP3 specific *** thus emphasize the requirement for more systematic studies that are designed to provide direct evidence to support the link,given that several studies have provided both direct and indirect evidence under specific *** editorial emphasizes that the current investigation should be circumspect in its conclusion,i.e.,not overemphasizing its role in the pathogenesis of DCM with the fact of only significantly increased expression or activation of NLRP3 inflammasome and pyroptosis in the heart of diabetic rodent *** clear-cut evidence-based causative roles of NLRP3 inflammasome and pyroptosis in the pathogenesis of DCM can help to develop effective and safe medications for the clinical management of DCM,targeting these biomarkers.

关键词： Diabetic cardiomyopathy Nucleotide oligomerization domain NOD-like receptor protein 3 inflammasome Cardiac cell death Pyroptosis

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SARS-CoV-2 variants are associated with different clinical courses in children with MIS-C

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World Journal of pediatrics 2024年第2期20卷 143-152页

作者： Andres F.Moreno Rojas Emelia Bainto Helen Harvey Adriana H.Tremoulet Jane C.Burns Kirsten B.Dummer department of pediatrics Division of Pediatric CardiologyUniversity of California San Diegoand Rady Children’s Hospital3020 Children’s Way MC 5004San DiegoCA 92123USA Kawasaki Disease research Center La JollaCAUSA department of pediatrics Division of Pediatric Critical CareUniversity of California San Diegoand Rady Children’s HospitalSan DiegoCAUSA department of pediatrics University of California San Diegoand Rady Children’s HospitalSan DiegoCAUSA

Background Recent infection with SARS‑CoV-2 in children has been associated with multisystem inflammatory syndrome in children(MIS-C).SARS‑CoV-2 has undergone different *** publications exist about specific variants and their correlation with the severity of *** This was a single-center,retrospective study including all patients admitted with MIS-C at Rady Children’s Hospital-San Diego between May 2020 and March *** epidemiologic data,including viral genomic information,were obtained from public ***,clinical presentation,laboratory values,and outcomes were obtained from electronic medical *** The analysis included 104 pediatric *** MIS-C waves were *** variants in San Diego during the first wave included clades 20A to *** the second wave,there were variants from clades 20A to C,20G,21C(Epsilon),20I(Alpha),and 20J(Gamma).The third wave had Delta strains(clades 21A,21I,and 21J),and the fourth had Omicron variants(clades 21K,21L,and 22C).MIS-C presented with similar symptoms and laboratory findings across all *** patients were admitted to the pediatric intensive care unit(PICU)(74%)and required inotropic support(63%)during the second *** of the patients required mechanical circulatory support,and only two required invasive ventilatory *** was no *** The various strains of SARS-CoV-2 triggered MIS-C with differing severities,with the second wave having a more severe clinical *** the differences in disease severity across variants were due to changes in the virus or other factors remains unknown.

关键词： Complications COVID-19 MIS-C SARS-CoV-2 variants

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Precise genome-editing in human diseases:mechanisms,strategies and applications

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1065-1085页

作者： Yanjiang Zheng Yifei Li Kaiyu Zhou Tiange Li Nathan J.VanDusen Yimin Hua Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE Department of PediatricsWest China Second University HospitalSichuan UniversityChengduSichuan 610041China department of Cardiovascular Surgery West China HospitalSichuan UniversityChengduSichuan 610041China department of pediatrics Herman B Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisIN 46202USA

Precise genome-editing platforms are versatile tools for generating specific,site-directed DNA insertions,deletions,and *** continuous enhancement of these tools has led to a revolution in the life sciences,which promises to deliver novel therapies for genetic *** genome-editing can be traced back to the 1950s with the discovery of DNA’s doublehelix and,after 70 years of development,has evolved from crude in vitro applications to a wide range of sophisticated capabilities,including in vivo ***,precise genome-editing faces constraints such as modest efficiency,delivery challenges,and off-target *** this review,we explore precise genome-editing,with a focus on introduction of the landmark events in its history,various platforms,delivery systems,and ***,we discuss the landmark events in the history of precise ***,we describe the current state of precise genome-editing strategies and explain how these techniques offer unprecedented precision and versatility for modifying the human ***,we introduce the current delivery systems used to deploy precise genome-editing components through DNA,RNA,and ***,we summarize the current applications of precise genome-editing in labeling endogenous genes,screening genetic variants,molecular recording,generating disease models,and gene therapy,including ex vivo therapy and in vivo therapy,and discuss potential future advances.

关键词： precise generating editing

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Insights on ZEB1-AS1:emerging role from cancer to neurodegeneration

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Neural Regeneration research 2024年第6期19卷 1187-1188页

作者： Stephana Carelli Federica Rey Erika Maghraby Cristina Cereda pediatric research Center“Romeo ed Enrica Invernizzi” Department of Biomedical and Clinical SciencesUniversity of MilanMilanItaly Center of Functional Genomics and Rare Diseases Department of PediatricsBuzzi Children’s HospitalMilanItaly department of Biology and Biotechnology“L.Spallanzani” University of PaviaPaviaItaly

Implications for lncRNAs in the central nervous system:Transcriptional dysregulation is a key contributor to the pathogenesis of a wide range of diseases and long non-coding RNAs(lncRNAs)are highly expressed in the nervous ***,amongst the over 50,000 lncRNAs expressed in the human genome,more than 40%are specifically expressed in the brain where their roles in brain development,neuron functions,maintenance.

关键词： ZEB1 diseases pathogenesis

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Nucleotide excision repair gene polymorphisms and hepatoblastoma susceptibility in Eastern Chinese children:A five-center case-control study

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Chinese Journal of Cancer research 2024年第3期36卷 298-305页

作者： Huimin Yin Xianqiang Wang Shouhua Zhang Shaohua He Wenli Zhang Hongting Lu Yizhen Wang Jing He Chunlei Zhou department of pediatric Surgery Guangzhou Institute of PediatricsGuangdong Provincial Key Laboratory of Research in Structural Birth Defect DiseaseGuangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510623China department of pediatric Surgery Senior Department of Pediatricsthe Seventh Center of Chinese People’s Liberation Army(PLA)General HospitalBeijing 100000China department of General Surgery Jiangxi Provincial Children’s HospitalNanchang 330006China department of pediatric Surgery Shengli Clinical Medical College of Fujian Medical UniversityFuzhou 350001China department of pediatric Surgery Qingdao Women and Children’s HospitalQingdao 266000China department of Pathology Anhui Provincial Children’s HospitalHefei 230051China department of Pathology Children’s Hospital of Nanjing Medical UniversityNanjing 210008China

Objective:Nucleotide excision repair(NER)plays a vital role in maintaining genome stability,and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under *** study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han ***:In this five-center case-control study,we enrolled 966 subjects from East China(193 hepatoblastoma patients and 773 healthy controls).The TaqMan method was used to genotype 19 single nucleotide polymorphisms(SNPs)in NER pathway genes,including ERCC1,XPA,XPC,XPD,XPF,and ***,multivariate logistic regression analysis was performed,and odds ratios(ORs)and 95%confidence intervals(95%CIs)were utilized to assess the strength of ***:Three SNPs were related to hepatoblastoma *** rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model(adjusted OR=1.49,95%CI=1.07−2.08,P=0.019;adjusted OR=1.66,95%CI=1.12−2.45,P=0.012,respectively).However,XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model(adjusted OR=0.68,95%CI=0.49−0.95;P=0.024).Stratified analysis demonstrated that these significant associations were more prominent in certain ***,there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci(eQTLs)and splicing quantitative trait loci(sQTLs)***:In summary,NER pathway gene polymorphisms(XPC rs2229090,XPD rs3810366,and XPD rs238406)are significantly associated with hepatoblastoma risk,and further research is required to verify these findings.

关键词： Nucleotide excision repair polymorphisms hepatoblastoma susceptibility

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Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo

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Oncology research 2024年第6期32卷 1109-1118页

作者： ZHIGANG XIA MENGYAO TIAN YUCAI CHENG WENFANG YI ZEFAN DU TIANWEN LI YUCHEN WEN LINDI LI YONG LIU CHUN CHEN pediatric Hematology Laboratory Division of Hematology/OncologyDepartment of PediatricsThe Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Scientific research Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological ***,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion *** and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell ***,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment ***:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological ***,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

关键词： CD19 CAR-T B-cell hematologic malignancies Metabolism In vivo

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Chemotherapy-induced small extracellular vesicles prime the pre-metastatic niche to accelerate neuroblastoma metastasis

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Genes & Diseases 2024年第4期11卷 65-68页

作者： Carson A.Wills Xiaoming Liu Longgui Chen Yuanjun Zhao Zhenqiu Liu Vladimir S.Spiegelman Jeffrey Sundstrom Hong-Gang Wang department of pediatrics Division of Pediatric Hematology and OncologyThe Pennsylvania State University Collegeof MedicinePA 17033USA department of Ophthalmology The Pennsylvania State University College of MedicinePA 17033USA department of Public Health Sciences The Pennsylvania StateUniversityCollegeofMedicinePA 17033USA

Neuroblastoma is the most common extracranial solid tumor in children,accounting for more than 10%of cancerrelated deaths in this *** standard of care for patients diagnosed with medium-to high-risk neuroblastoma,incl... 详细信息

关键词： neuroblastoma metastatic metastasis

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Anticancer effects of exercise:Insights from single-cell analysis

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Journal of Sport and Health Science 2024年第5期13卷 676-678页

作者： Abel Plaza-Florido Alejandro Lucia Shlomit Radom-Aizik Carmen Fiuza-Luces pediatric Exercise and Genomics research Center Department of PediatricsSchool of MedicineUniversity of California IrvineIrvineCA 92617USA Faculty of Sport Sciences Universidad Europea de MadridMadrid 28670Spain Physical Activity and Health research Group(“PaHerg”) Research Institute of the Hospital 12 de Octubre(“imas12”)Madrid 28041Spain

A recent special topic in the Journal of Sport and Health Science reported the health benefits conferred by traditional and innovative m-health exercise and multimodal programs with respect to several types of cancer.... 详细信息

关键词： protective exercise modal

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Advancing pediatric exercise research:A focus on immunomics and cutting-edge technologies

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Journal of Sport and Health Science 2024年第5期13卷 679-681页

作者： Abel Plaza-Florido Alejandro Lucia Shlomit Radom-Aizik pediatric Exercise and Genomics research Center Department of PediatricsSchool of MedicineUniversity of California at IrvineIrvineCA 92617USA Faculty of Sport Sciences Universidad Europea de MadridMadrid 28670Spain Physical Activity Health research Group(“PaHerg”) Research Institute of Hospital 12 de Octubre(“imas12”)Madrid 28041Spain

*** importance of immunomics in pediatric exercise research The profound effect that"acute"or"regular"exercise(i.e.,a single exercise session or repeated sessions over time,respectively)exerts on the immune system has been widely recognized.1 Acute exercise is largely"immuno-enhancing"(e.g.,it may even improve vaccine responses in"at-risk"patients),whereas regular exercise reduces the risk of chronic conditions(not only obesity,diabetes,or cardiovascular diseases,but also several types of cancer)partly due to its anti-inflammatory effects.

关键词： pediatric Acute vaccine

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Novel de novo TRPV4 mutation identified in a Chinese family with metatropic dysplasia inhibits chondrogenic differentiation

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Genes & Diseases 2024年第3期11卷 83-86页

作者： Ping Wei Weizhe Shi Tianying Nong Caixia Xian Xia Li Zhaohui Li Xin Li Jianping Wu Liyuan Shang Fulong Xu Yibo Xu Hongwen Xu Mingwei Zhu Guangzhou Institute of pediatrics Guangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouGuangdong 510623China department of pediatric Orthopedics Guangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouGuangdong 510623China

Metatropicdysplasia(MD,MIM156530)is a rare congenital bone dysplasia primarily characterized by severe platyspondyly with long and wide vertebral bodies and dumbbell deformity of the tubular *** can be caused by heterozygous mutations in the gene encoding transient receptor potential vanilloid family member 4(TRPV4).We identifieda novel de novo mutation,c.2353T>C,in the TRPV4 gene,in a Chinese family with mild MD.

关键词： TRPV4 dysplasia congenital

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