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Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 568-580页

作者： Hao ZHANG Xinshu WANG Bo HU Peicheng LI Yierfan ABUDUAINI Hongmei ZHAO Ayinaer JIEENSIHAN Xishuang CHEN Shiyu WANG Nuojin GUO Jian YUAN Yunhui LI Lei LI Yuntong YANG Zhongmin LIU Zhaosheng TANG Hua WANG Department of Endocrinology Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Research Center for Translational Medicine Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Department of Cardiology Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China Department of Biochemistry and Molecular Biology School of MedicineTongji UniversityShanghai 200331China Shanghai Institute of Stem cell Research and Clinical Translation Shanghai East HospitalShanghai 200120China Ji’an Hospital Shanghai East HospitalJi’an 343000China

diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA *** umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)***-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains *** this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with *** glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were *** that interacted with IGF1R were determined through coimmunoprecipitation *** expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot ***-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of *** identification of the morphology and phenotype of HUcMSC was performed by way of oil red“O”staining and Alizarin red *** rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and ***1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown *** cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin *** infusion ameliorated abnormalities and preserved kidney structure and function in DM *** expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased sign

关键词： Insulin-like growth factor 1 receptor(IGF1R) Checkpoint kinase 2(CHK2) Protein 53(p53) Diabetes mellitus Human umbilical cord mesenchymal stem cell(HUcMSC) DNA damage repair

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Effects of Moringa oleifera aqueous extract on the growth performance,blood characteristics,and histological features of gills and livers in Nile tilapia

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Aquaculture and Fisheries 2024年第1期9卷 85-92页

作者： Mahamoud A.Emam Ramy M.Shourbela Waleed N.El-Hawarry Seham Y.Abo-Kora Fatma Abdel-Monem Gad Ashraf M.Abd El-latif Mahmoud A.O.Dawood Histology Department Faculty of Veterinary MedicineBenha UniversityBenha13511Egypt Department of Animal Husbandry and Animal Wealth Development Faculty of Veterinary MedicineAlexandria UniversityAlexandria22758Egypt Pharmacology Department Faculty of Veterinary MedicineBenha UniversityBenha13511Egypt Clinical Pathology Department Faculty of Veterinary MedicineBenha UniversityBenha13511Egypt Department of Aquatic Animal Diseases and Management Faculty of Veterinary MedicineBenha UniversityBenha13511Egypt Animal production Department Faculty of AgricultureKafrelsheikh UniversityKafr El-Sheikh33511Egypt The Center for Applied Research on the Environment and Sustainability The American University in CairoCairo11835Egypt

Moringa oleifera is well known as a highly nutritious plant and a water purifier in fish *** fish has many impressive qualities making them very suitable for ***,this study aimed to evaluate the effect of supplementation of Moringa oleifera aqueous extract(MOAE)at varying concentrations(0,100,200,and 400 mg/kg diet for 90 days)on growth performance,hematological,and some biochemical parameters of Nile ***,histological changes and immunohistochemical expression of caspase 3 in gills and livers were *** enhancements(Pcells,hemoglobin,packed cell volume,white blood cells,and total serum protein were observed in fish fed 200 mg MOAE/kg diet compared with other ***,a significant reduction(Pimmune expressions of caspase 3 were determined where gills and liver of fish fed 400 mg MOAE/kg diet revealed extensive number of positive caspase 3 cells indicating severe apoptotic ***,a dietary MOAE at 200 mg/kg diet is recommended to improve the growth performance,hematological parameters,liver and kidney functions in Nile ***,caution must be considered when using MOAE at a concentration over 200 mg/kg diet.

关键词： Growth performance Liver Gills Moringa oleifera Nile tilapia

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The membrane-associated ubiquitin ligases MARCH2 and MARCH3 target IL-5 receptor alpha to negatively regulate eosinophilic airway inflammation

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cellular & Molecular Immunology 2022年第10期19卷 1117-1129页

作者： Lin-Wen Zeng Lu Feng Rui Liu Heng Lin Hong-Bing Shu Shu Li Department of Infectious Diseases Zhongnan Hospital of Wuhan UniversityMedical Research InstituteFrontier Science Center for Immunology and MetabolismResearch Unit of Innate Immune and Inflammatory Diseases(2019RU063)Chinese Academy of Medical SciencesWuhan UniversityWuhan430071China

Interleukin 5(IL-5)plays crucial roles in type 2-high asthma by mediating eosinophil maturation,activation,chemotaxis and *** of IL-5 signaling is considered a strategy for asthma ***,we identified MARCH2 and MARCH3 as critical negative regulators of IL-5-triggered ***2 and MARCH3 associate with the IL-5 receptorαchain(IL-5Rα)and mediate its K27-linked polyubiquitination at K379 and K383,respectively,and its subsequent lysosomal *** of MARCH2 or MARCH3 modestly increases the level of IL-5Rαand enhances IL-5-induced signaling,whereas double knockout of MARCH2/3 has a more dramatic ***2/3 double knockout markedly increases the proportions of eosinophils in the bone marrow and peripheral blood in *** knockout of March2/3 aggravates ovalbumin(OVA)-induced eosinophilia and causes increased inflammatory cell infiltration,peribronchial mucus secretion and production of Th2 *** of Il-5 attenuates OVA-induced airway inflammation and the enhanced effects of March2/3 double *** findings suggest that MARCH2 and MARCH3 play redundant roles in targeting IL-5Rαfor degradation and negatively regulating allergic airway inflammation.

关键词： MARCH2/3 IL-5Rα Polyubiquitination Eosinophil Airway inflammation

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Puerarin inhibits inflammation and lipid accumulation in alcoholic liver disease through regulating MMP8

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Chinese Journal of Natural Medicines 2023年第9期21卷 670-681页

作者： HU Ying WANG Shuxian WU Lan YANG Kai YANG Fan YANG Junfa HU Shuang YAO Yan XIA Xun LIU Yixin PENG Li WAN Jihong SHEN Chuanpu XU Tao Inflammation and immune Mediated Diseases Laboratory of Anhui Province School of PharmacyAnhui Medical UniversityHefei 230032China Institute for Liver Diseases of Anhui Medical University Hefei 230032China Medical Device production Supervision Office Anhui Provincial Drug AdministrationHefei 230051China Department of Ophthalmology the First Affiliated Hospital of Anhui Medical UniversityHefei 230022China

Alcoholic liver disease(ALD)is a growing global health concern,and its early pathogenesis includes steatosis and *** lipid accumulation and inflammation is a crucial step in relieving *** shows that puerarin(Pue),an isoflavone isolated from Pueraria lobata,exerts cardio-protective,neuroprotective,anti-inflammatory,antioxidant ***,the therapeutic potential of Pue on ALD remains *** the study,both the NIAAA model and ethanol(EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related *** results showed that Pue(100 mg·kg^(−1))attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c,TNF-α,IL-6 and IL-1β,compared with silymarin(Sil,100 mg·kg^(−1)).In vitro results were consistent with in vivo ***,Pue might suppress liver lipid accumulation and inflammation by regulating *** conclusion,Pue might be a promising clinical candidate for ALD treatment.

关键词： Puerarin MMP8 Alcoholic liver disease Inflammatory Lipid accumulation

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CD36 promotes tubular ferroptosis by regulating the ubiquitination of FSP1 in acute kidney injury

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Genes & Diseases 2024年第1期11卷 449-463页

作者： Yixin Ma Lili Huang Zheng Zhang Pengfei Yang Qingsong Chen Xujia Zeng Fangyan Tan Chunxia Wang Xiongzhong Ruan Xiaohui Liao Department of Nephrology The Second Affiliated HospitalChongqing Medical UniversityChongqing 400010China Department of cell Biology and Genetics Chongqing Medical UniversityChongqing 400016China Centre for Nephrology Royal Free and University College Medical SchoolUniversity College LondonRoyal Free CampusRowland Hill StreetLondon NW32PFUnited Kingdom Centre for Lipid Research Key Laboratory of Molecular Biology on Infectious DiseasesMinistry of EducationChongqing Medical UniversityChongqing 400016China Kuanren Laboratory of Translational Lipidology Centre for Lipid ResearchSecond Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

Reactive oxidative species(ROos)production-driven ferroptosis plays a role in acute kidney injury(Akl).However,its exact molecular mechanism is poorly *** receptor CD36 has important roles in oxidizing lipids,lipid accumulation,metabolic syndrome,and insulin resistance in chronic kidney disease,but its roles remain unexplored in *** present study investigated the role and mechanism of CD36 in regulating proximal tubular cell ferroptosis and *** expression of CD36 was found to be significantly up-regulated in AKI renal tissues and correlated with renal function,which might serve as an independent biomarker for AKl ***,in adult mice subjected to AKl,deletion of CD36(CD36-/-)induced tubular cell Ros accumulation,ferroptosis activation,and renal ***,combining LC-MS/MS,co-IP,and ubiquitination analyses revealed that CD36 could specifically bind to ferroptosis suppressor protein 1(FSP1)and regulate its ubiquitination at sites K16 and K24,leading to FSP1 degradation and progression of ferroptosis in *** present results emphasize a novel mechanism of CD36 in cisplatin-induced *** discovery of the special CD36 roles in promoting ferroptosis and AKI development by regulating the ubiquitination of FSP1 in proximal tubular cells may be potential therapeutic targets for ***,CD36 may play a key role in the progression of ***,targeting CD36 may provide a promising treatment option for AKI.

关键词： Acute kidney injury CD36 Ferroptosis FSP1 Ubiquitin-dependent degradation

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Automated closed-cell production platform solves dilemma of industrial-scale manufacturing for mesenchymal stromal cell-based therapy

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Journal of Pharmaceutical Analysis 2023年第11期13卷 1233-1234页

作者： Yirui Feng Bin Wang Clinical Stem cell Center The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing210000China School of Life Science Nanjing UniversityNanjing210000China

Mesenchymal stromal cells(MSCs),known for their therapeutic bioactivity,find widespread application as cellular drugs for treating various *** obtained from patients or donors require extensive large-scale expansion for clinical ***,the conventional method of cultivating MSCs involves several manual processes and yields inconsistent batch-to-batch ***,it has not been scalable as a cell therapy[1].To overcome the limitations of conventional planar cell culture,van Wezel initially proposed a system for culturing cells in suspension using microcarriers and successfully proliferated rabbit embryonic skin cells and human embryonic lung cells[2].Subsequently,microcarrier technology has been employed across various pharmaceutical applications,leading to the development and commercialization of a diverse array of microcarriers with distinct physicochemical properties.

关键词： rabbit drugs batch

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Single-cell characterization of major components of plant cell walls in situ by Raman spectroscopy

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Science China(Life Sciences) 2024年第8期67卷 1772-1774页

作者： Yujian Li Weiwei Shen Xi Zhang Yaning Cui Yuanyuan Zhao Yayu Guo Xiaojuan Li Shuizhong Wang Guoyong Song Pu Wang Jianfeng Ma Jinxing Lin State Key Laboratory of Efficient production of Forest Resources College of Biological Sciences and TechnologyBeijing Forestry UniversityBeijing 100083China Institute of Tree Development and Genome Editing Beijing Forestry UniversityBeijing 100083China National Engineering Research Center of Tree Breeding and Ecological Restoration College of Biological Sciences and TechnologyBeijing Forestry UniversityBeijing 100083China Beijing Key Laboratory of Lignocellulosic Chemistry Engineering Research Center of Forestry Biomass Materials and EnergyMinistry of EducationBeijing Forestry UniversityBeijing 100083China Beijing Advanced Innovation Center for Biomedical Engineering School of Biological Science and Medical EngineeringBeihang UniversityBeijing 100191China Key lab of Bamboo and Rattan Science&Technology International Center for Bamboo and RattanBeijing 100102China

Dear Editor,Plant cell walls are complex and dynamic structures that are mainly composed of polysaccharide polymers such as cellulose,hemicellulose,and pectin,in addition to substantial amounts of the non-saccharide polymer lignin(McFarlane et al.,2014;German et al.,2023).The components of cell walls are interconnected in various ways to form a complex,multilayered network structure(Wen et al.,2023).

关键词： walls cellulose characterization

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Investigation of multi-step fast charging protocol and aging mechanism for commercial NMC/graphite lithium-ion batteries

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Journal of Energy Chemistry 2023年第5期80卷 237-246,I0006页

作者： Yaqi Li Jia Guo Kjeld Pedersen Leonid Gurevich Daniel-Ioan Stroe Department of Materials and production Aalborg UniversityAalborg 9220Denmark Department of Energy Aalborg UniversityAalborg 9220Denmark

Fast charging is considered a promising protocol for raising the charging efficiency of electric ***,high currents applied to Lithium-ion(Li-ion)batteries inevitably accelerate the degradation and shorten their *** work designs a multi-step fast-charging method to extend the lifetime of LiNi0.5Co0.2Mn0.3O2(NMC)/graphite Li-ion batteries based on the studies of half cells and investigates the aging mechanisms for different charging *** degradation has been studied from both full cell behaviour and materials perspectives through a combination of non-destructive diagnostic methods and post-mortem *** the proposed multi-step charging protocol,the state-of-charge(SOC)profile is subdivided into five ranges,and the charging current is set differently for different SOC *** of the designed multi-step fast charging protocols is shown to allow for a 200 full equivalent cycles longer lifetime as compared to the standard charging method,while the charging time is reduced by 20%.From the incremental capacity analysis and electrical impedance spectroscopy,the loss of active materials and lithium inventory on the electrodes,as well as an increase in internal resistance for the designed multistep constant-current-constant-voltage(MCCCV)protocol have been found to be significantly lower than for the standard charging ***-mortem analysis shows that cells aged by the designed MCCCV fast charging protocol exhibit less graphite exfoliation and crystallization damage,as well as a reduced solid electrolyte interphase(SEI)layer growth on the anode,leading to a lower Rseiresistance and extended lifetime.

关键词： Fast-charging Lithium-ion battery Aging mechanism Electrode

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Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice

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International Journal of Oral Science 2022年第3期14卷 371-380页

作者： Yumei Lai Wei Zheng Minghao Qu Christopher C.Xiao Sheng Chen Qing Yao Weiyuan Gong Chu Tao Qinnan Yan Peijun Zhang Xiaohao Wu Guozhi Xiao Department of Orthopedic Surgery Rush University Medical CenterChicagoILUSA Department of Orthopaedic Center Xinjiang Production and Construction Corps HospitalUrumqiChina Department of Biochemistry School of MedicineSouthern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentShenzhenChina Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint(TMJ) osteoarthritis(OA);however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4(Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore,Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.

关键词： Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice TMJ

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Developmental dynamics of the single nucleus regulatory landscape of pig hippocampus

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Science China(Life Sciences) 2023年第11期66卷 2614-2628页

作者： Siyu Yang Dong Chen Lei Xie Xiaoxiao Zou Yanyuan Xiao Lin Rao Tianxiong Yao Qing Zhang Liping Cai Fei Huang Bin Yang Lusheng Huang State Key Laboratory of Pig Genetic Improvement and production Technology Jiangxi Agricultural UniversityNanchang 330045China

The hippocampus is a brain region associated with memory,learning and spatial navigation,its aging-related dysfunction is a common sign of Alzheimer’s *** is a good model for human neurodegenerative disease,but our understanding of the regulatory program of the pig hippocampus and its cross-species conservation in humans remains ***,we profiled chromatin accessibility in 33,409 high-quality nuclei and gene expression in 8,122 high-quality nuclei of the pig hippocampus at four postnatal *** identified 510,908 accessible chromatin regions(ACRs)in 12 major cell types,among which progenitor cells such as neuroblasts and oligodendrocyte progenitor cells showed a dynamic decrease from early to later developmental *** revealed significant enrichment of transposable elements in cell type-specific ACRs,particularly in *** identified oligodendrocytes as the most prominent cell type with the greatest number of genes that showed significant changes during the *** identified ACRs and key transcription factors underlying the trajectory of neurogenesis(such as POU3F3 and EGR1)and oligodendrocyte differentiation(RXRA and FOXO6).We examined 27 Alzheimer’s disease-related genes in our data and found that 15 showed cell type-specific activity(TREM2,RIN3 and CLU),and 15 genes displayed age-associated dynamic activity(BIN1,RABEP1 and APOE).We intersected our data with human genome-wide association study results to detect neurological disease-associated cell *** present study provides a single nucleusaccessible chromatin landscape of the pig hippocampus at different developmental stages and is helpful for the exploration of pigs as a biomedical model in human neurodegenerative diseases.

关键词： hippocampus pig chromatin accessibility gene expression nuclei accessible chromatin regions development

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