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Cardiac regeneration: Pre-existing cardiomyocyte as the hub of novel signaling pathway

Genes & Diseases 2024年第2期11卷 747-759页

作者： Tao Wang Xinzhe Chen Kai Wang Jie Ju Xue Yu Wanpeng Yu Cuiyun Liu Yin Wang institute for translational medicine The Affiliated Hospital of Qingdao UniversityCollege of MedicineQingdao UniversityQingdaoShandong 266023China College of medicine Qingdao UniversityQingdaoShandong 266023China

In the mammalian heart,cardiomyocytes are forced to withdraw from the cell cycle shortly after birth,limiting the ability of the heart to regenerate and *** development of multimodal regulation of cardiac proliferation has verified that pre-existing cardiomyocyte proliferation is an essential driver of cardiac *** the continuous development of genetic lineage tracking technology,it has been revealed that cell cycle activity produces polyploid cardiomyocytes during the embryonic,juvenile,and adult stages of cardiogenesis,but newly formed mononucleated diploid cardiomyocytes also elevated sporadically during myocardial *** implied that adult cardiomyocytes have a weak regenerative capacity under the condition of ischemia injury,which offers hope for the clinical treatment of myocardial ***,the regeneration frequency and source of cardiomyocytes are still low,and the mechanism of regulating cardiomyocyte proliferation remains further *** is noteworthy to explore what force triggers endogenous cardiomyocyte proliferation and heart ***,we focused on summarizing the recent research progress of emerging endogenous key modulators and crosstalk with other signaling pathways and furnished valuable insights into the internal mechanism of heart *** addition,myocardial transcription factors,non-coding RNAs,cyclins,and cell cycle-dependent kinases are involved in the multimodal regulation of pre-existing cardiomyocyte ***,awakening the myocardial proliferation endogenous modulator and regeneration pathways may be the final battlefield for the regenerative therapy of cardiovascular diseases.

关键词： Cardiac regeneration Cell cycle re-enter Myocardial infarction Pre-existing cardiomyocyte proliferation Regenerative therapy of cardiovascular diseases

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Emerging role of regulated cell death in intestinal failure-associated liver disease

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 228-233页

作者： Si-Yang Cheng Lu Jiang Ying Wang Wei Cai Department of pediatric Surgery Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China Shanghai Key Laboratory of pediatric Gastroenterology and Nutrition Shanghai 200092China Shanghai institute for pediatric Research Shanghai 200092China Division of pediatric Gastroenterology and Nutrition Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China

Intestinal failure-associated liver disease(IFALD)is a common complication of long-term parenteral nutrition that is associated with significant morbidity and *** is mainly characterized by cholestasis in children and steatohepatitis in ***,there is no effective approach to prevent or reverse the *** cell death(RCD)represents a fundamental biological paradigm that determines the outcome of a variety of liver *** cell death is reclassified into several types,based on the mechanisms and morphological *** evidence has linked different modes of RCD,such as apoptosis,necroptosis,ferroptosis,and pyroptosis to the pathogenesis of liver *** studies have shown that different modes of RCD are present in animal models and patients with *** the pathogenic roles of cell death may help uncover the underlying mechanisms and develop novel therapeutic strategies in *** this review,we discuss the current knowledge on how RCD may link to the pathogenesis of *** highlight examples of cell death-targeted interventions aiming to attenuate the disease,and provide perspectives for future basic and translational research in the field.

关键词： Parenteral nutrition Apoptosis Necroptosis Cholestasis Steatosis

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Editorial Commentary:Copper Homeostasis in Neurodegenerative Diseases

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Current Medical Science 2024年第1期44卷 244-245页

作者： Ying-hui LI Kun WANG institute for translational medicine The Affiliated Hospital of Qingdao UniversityCollege of MedicineQingdao UniversityQingdao 266021China

Copper,as an essential trace nutrient,plays a crucial role in biological processes such as mitochondrial respiration,antioxidant stress response,and the synthesis of ***,cellular copper concentrations are maintained at very low levels,a pattern also observed in cancer cells to prevent adverse consequences of copper overload,such as *** involves copper dependency,accumulation of lipidated proteins,and a reduction in Fe-S cluster proteins[1].Various neurodegenerative diseases are associated with imbalances in copper homeostasis.

关键词： copper Copper consequences

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RNPS1 stabilizes NAT10 protein to facilitate translation in cancer via tRNA ac^(4)C modification

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International Journal of Oral Science 2024年第1期16卷 73-84页

作者： Xiaochen Wang Rongsong Ling Yurong Peng Weiqiong Qiu Demeng Chen Center For translational medicine the First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina institute for Advanced Study Shenzhen UniversityShenzhenChina

Existing studies have underscored the pivotal role of N-acetyltransferase 10(NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma(HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1(RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6(ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac^(4)C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel t RNA-ac^(4)C modification sites, thereby providing a potent sequencing tool for tRNAac^(4)C research. Our findings expand the repertoire of tRNA ac^(4)C modifications and identify a role of tRNA ac^(4)C in the regulation of mRNA translation in HNSCC.

关键词： NAT1 thereby translation

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Engineered plant extracellular vesicles for autoimmune diseases therapy

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Nano Research 2024年第4期17卷 2857-2873页

作者： Ruina Han Yan Wu Yafei Han Xiangfei Liu Han Liu Jiacan Su institute of translational medicine Shanghai UniversityShanghai 200444China Organoid Research Center Shanghai UniversityShanghai 200444China National Center for translational medicine(Shanghai)SHU Branch Shanghai UniversityShanghai 200444China Department of Orthopedics Shanghai Zhongye HospitalShanghai 200941China Department of Orthopedics Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China

Autoimmune diseases(AID)encompass a diverse array of conditions characterized by immune system dysregulation,resulting in aberrant responses of B cells and T cells against the body’s own healthy *** extracellular vesicles(PEVs)are nanoscale particles enclosed by phospholipid bilayers,secreted by plant cells,which facilitate intercellular communication by transporting various bioactive *** to their nanoscale structure,safety,abundant sources,low immunogenicity,high yield,biocompatibility,and effective targeting of the colon and liver,PEVs are regarded as a promising platform for the treatment of *** review provides a comprehensive summary of PEV biogenesis,physicochemical and biological properties,internalization mechanisms,isolation methods,and their applications in various diseases,with a specific focus on their potential roles in ***,we propose engineering approaches and administration methods for ***,we present an overview of the advantages and challenges associated with utilizing PEVs for the treatment of *** gaining a comprehensive understanding of PEVs,we anticipate the development of innovative therapeutic strategies for *** and engineered PEVs hold substantial promise as a valuable resource for innovative technologies in AID treatment.

关键词： autoimmune diseases plant extracellular vesicles extracellular vesicles engineering modification

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Longitudinal changes in body weight of breastfeeding mothers in the first year after delivery and its relationship with human milk composition:a combined longitudinal and cross-sectional cohort study

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Food Science and Human Wellness 2024年第1期13卷 254-264页

作者： Huijuan Ruan Yajie Zhang Qingya Tang Xuan Zhao Xuelin Zhao Yi Xiang Wei Geng Yi Feng Wei Cai Department of Clinical Nutrition Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Shanghai Key Laboratory of pediatric Gastroenterology and Nutrition Shanghai Institute of Pediatric ResearchShanghai 200092China Department of pediatric Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China

Objective:Postpartum weight retention(PPWR)is a common problem among women after *** main objectives of this study are to understand the changes in body weight of breastfeeding mothers during long-term follow-up and preliminarily explore the relationship between maternal body weight and human milk composition,including macronutrients,leptin,and ***:The study included a longitudinal cohort(122 mothers),and a cross-sectional cohort(37 mothers).The human milk,maternal weight,and dietary surveys were collected in the longitudinal cohort at different follow-up time points(1-14 days postpartum,2-4 months postpartum,5-7 months postpartum,and 12-17 months postpartum).The maternal body weight was analyzed using the responses in the survey questionnaires.A milk analyzer based on the mid-infrared spectroscopy(MIRS)was used to determine milk composition,and nutrition analysis software evaluated dietary *** the cross-sectional cohort,participating mothers were asked to provide blood and human milk samples and pertinent information related to maternal body *** body composition was measured by bioelectrical impedance analysis(BIA),while ELISA analyzed leptin and adiponectin in milk and ***:At 5-7 months postpartum,the PPWR of breastfeeding mothers was(2.46±3.59)*** 12-17 months postpartum,the PPWR was(0.98±4.06)*** was found to be negatively correlated with milk fat content within 14 days postpartum and positively correlated at 2-4 months *** addition,the maternal weight and body muscle mass were positively correlated with leptin and adiponectin in *** leptin was positively correlated with the mother’s body weight,body mass index(BMI),FAT percentage,and body fat mass,while plasma adiponectin did not correlate with any *** results also indicate that the PPWR did not correlate with leptin and adiponectin in plasma or ***:Breastfeeding mothers may retain considerable weight gai

关键词： Human milk Milk composition Body weight Body mass index(BMI) Weight gain Postpartum weight retention

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Rapid and chemoselective imidation of sulfides in aqueous buffer enabled by a novel guanidine-derived N-O reagent

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Science China Chemistry 2024年第6期67卷 1929-1934页

作者： Hanzheng Li Long Xu Jiajia Dong Key Laboratory of Organofluorine Chemistry Center for Excellence in Molecular SynthesisShanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai200032China institute of translational medicine National Facility for Translational Medicine(Shanghai)Shanghai Jiao Tong UniversityShanghai200240China School of Chemistry and Chemical Engineering Zhangjiang Institute for Advanced StudyShanghai Jiao Tong UniversityShanghai200240China Shanghai Artificial Intelligence Laboratory Shanghai200232China

Herein we report the facile synthesis of a series of novel N-O reagents and identify N′-di-Boc-N′′-[(mesitylsulfonyl)oxy]-guanidine as an efficient imidating *** reagent is synthetically scalable and bench-stable,yet it shows unprecedented reactivity and chemoselectivity towards S(II)in buffer/hexafluoroisopropanol(HFIP)system,to generate a new class of Nguanyl *** transformation of N-guanyl sulfilimines to N-guanyl sulfoximines provides us a chance to investigate these rarely reached compounds,which are shown to be versatile precursors to a variety of N-heterocyclic and *** work provides an addition to the tool box of both sulfur imidation and guanidine synthesis,especially for the need of rapid and selective modifications of sulfur(II)center under biocompatible conditions.

关键词： sulfur imidation N-O reagent

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Childhood sleep:physical,cognitive,and behavioral consequences and implications

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World Journal of pediatrics 2024年第2期20卷 122-132页

作者： Jianghong Liu Xiaopeng Ji Susannah Pitt Guanghai Wang Elizabeth Rovit Terri Lipman Fan Jiang School of Nursing University of Pennsylvania418 Curie Blvd.Room 424Claire M.Fagin HallPhiladelphiaPA 19104USA College of Health Sciences University of DelawareNewarkDE 19716USA Geisinger Commonwealth School of medicine ScrantonPA 18510USA pediatric translational medicine institute Department of Developmental and Behavioral PediatricsSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background Sleep problems in children have been increasingly recognized as a major public health *** research has extensively studied and presented many risk factors and potential mechanisms for children’s sleep *** this paper,we aimed to identify and summarize the consequences and implications of child sleep *** sources A comprehensive search for relevant English language full-text,peer-reviewed publications was performed focusing on pediatric sleep studies from prenatal to childhood and adolescence in a variety of indexes in PubMed,SCOPUS,and Psych Info published in the past two *** relevant data-based articles and systematic reviews are *** Many adverse consequences are associated with child sleep deficiency and other sleep problems,including physical outcomes(e.g.,obesity),neurocognitive outcomes(e.g.,memory and attention,intelligence,academic performance),and emotional and behavioral outcomes(e.g.,internalizing/externalizing behaviors,behavioral disorders).Current prevention and intervention approaches to address childhood sleep problems include nutrition,exercise,cognitive–behavioral therapy for insomnia,aromatherapy,acupressure,and *** interventions may be particularly important in the context of coronavirus disease *** research and policy strategies can target the risk factors of child sleep as well as the efficacy and accessibility of *** Given the increasing prevalence of child sleep problems,which have been shown to affect children’s physical and neurobehavioral wellbeing,understanding the multi-aspect consequences and intervention programs for childhood sleep is important to inform future research direction as well as a public health practice for sleep screening and intervention,thus improving sleep-related child development and health.

关键词： Behavior Child sleep Consequences Implications Neurocognitive Physical Prevention/intervention

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EHMT2 promotes tumorigenesis in GNAQ/11-mutant uveal melanoma via ARHGAP29-mediated RhoA pathway

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1187-1203页

作者： Yongyun Li Tianyu Zhu Jie Yang Qianqian Zhang Shiqiong Xu Shengfang Ge Renbing Jia Jianming Zhang Xianqun Fan Department of Ophthalmology Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200001China Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology Shanghai 200001China National Research Center for translational medicine(Shanghai) State Key Laboratory of Medical GenomicsShanghai Institute of HematologyRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China institute of translational medicine Zhangjiang Institute for Advanced StudyShanghai Jiao Tong UniversityShanghai 200240China

Constitutive activation of GNAQ/11 is the initiative oncogenic event in uveal melanoma(UM).Direct targeting GNAQ/11 has yet to be proven feasible as they are vital for a plethora of cellular *** search of genetic vulnerability for UM,we found that inhibition of euchromatic histone lysine methyltransferase 2(EHMT2)expression or activity significantly reduced the proliferation and migration capacity of cancer ***,elevated expression of EHMT2 had been validated in UM ***,Kaplan-Meier survival analysis indicated high EHMT2 protein level was related to poor recurrence-free survival and a more advanced T *** immunoprecipitation sequencing analysis and the following mechanistic investigation showed that ARHGAP29 was a downstream target of *** transcription was suppressed by EHMT2 in a methyltransferasedependent pattern in GNAQ/11-mutant UM cells,leading to elevated RhoA *** constitutively active RhoA in UM cells lacking EHMT2 restored oncogenic *** blocking EHMT2 and GNAQ/11 signaling in vitro and in vivo showed a synergistic effect on UM growth,suggesting the driver role of these two key *** summary,our study shows evidence for an epigenetic program of EHMT2 regulation that influences UM progression and indicates inhibiting EHMT2 and MEK/ERK simultaneously as a therapeutic strategy in GNAQ/11-mutant UM.

关键词： Uveal melanoma EHMT2 RhoA pathway ARHGAP29 G protein GNAQ GNA11

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Progranulin:A promising biomarker and therapeutic target for fibrotic diseases

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3312-3326页

作者： Fan Yang Ming-Han Cheng Hai-Feng Pan Jian Gao pediatric translational medicine institute Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghai 200000China Department of Ophthalmology the First Affiliated Hospital of Anhui Medical UniversityHefei 230022China Department of Epidemiology and Biostatistics School of Public HealthAnhui Medical UniversityHefei 230022China Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Hefei 230022China

Progranulin(PGRN),a multifunctional growth factor-like protein expressed by a variety of cell types,serves an important function in the physiologic and pathologic processes of fibrotic diseases,including wound healing and the inflammatory *** was discovered to inhibit proinflammation effect by competing with tumor necrosis factor-alpha(TNF-a)binding to TNF ***,excessive tissue repair in the development of inflammation causes tissue *** investigations have indicated the significance of PGRN in regulating inflammatory ***,multiple studies have shown that PGRN was linked to fibrogenesis,and was considered to monitor the formation of fibrosis in multiple organs,including liver,cardiovascular,lung and *** paper is a comprehensive review summarizing our current knowledge of PGRN,from its discovery to the role in *** is followed by an in-depth look at the characteristics of PGRN,consisting of its structure,basic function and intracellular ***,we will discuss the potential of PGRN in the diagnosis and treatment of fibrosis.

关键词： Progranulin Fibrotic disease Fibrosis Inflammation Biomarker Therapeutic target PGRN/TNFR interaction Signaling pathway

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