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Ferroptosis inhibitors reduce celastrol toxicity and preserve its insulin sensitizing effects in insulin resistant HepG2 cells

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Journal of Integrative Medicine 2024年第3期22卷 286-294页

作者： Jia-jia Liu Xue Zhang Bang-lan Cai Man-man Qi Yong-bin Chi Bin Peng Deng-hai Zhang School of Medicine Shanghai UniversityShanghai 200444China Shanghai Health Commission Key Lab of Artificial Intelligence-Based Management of Inflammation and Chronic Diseases Shanghai Pudong Gongli HospitalSecondary Military Medical UniversityShanghai 200135China School of Basic Medicine Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina

Objective:Research has shown that celastrol can effectively treat a variety of diseases,yet when passing a certain dosage threshold,celastrol becomes toxic,causing complications such as liver and kidney damage and erythrocytopenia,among *** this dichotomy in mind,it is extremely important to find ways to preserve celastrol’s efficacy while reducing or preventing its ***:In this study,insulin-resistant Hep G2(IR-Hep G2)cells were prepared using palmitic acid and used for in vitro ***-Hep G2 cells were treated with celastrol alone or in combination with Nacetylcysteine(NAC)or ferrostatin-1(Fer-1)for 12,24 or 48 h,at a range of *** counting kit-8assay,Western blotting,quantitative reverse transcription-polymerase chain reaction,glucose consumption assessment,and flow cytometry were performed to measure celastrol’s cytotoxicity and whether the cell death was linked to ***:Celastrol treatment increased lipid oxidation and decreased expression of anti-ferroptosis proteins in IR-Hep G2 *** downregulated glutathione peroxidase 4(GPX4)m *** docking models predicted that solute carrier family 7 member 11(SLC7A11)and GPX4 were covalently bound by ***,we found for the first time that the application of ferroptosis inhibitors(especially NAC)was able to reduce celastrol’s toxicity while preserving its ability to improve insulin sensitivity in IR-Hep G2 ***:One potential mechanism of celastrol’s cytotoxicity is the induction of ferroptosis,which can be alleviated by treatment with ferroptosis *** findings provide a new strategy to block celastrol’s toxicity while preserving its therapeutic effects.

关键词： Celastrol Insulin resistance Ferroptosis N-Acetylcysteine Palmitic acid Molecular docking

Efficacy of physiological seawater nasal irrigation for the treatment of children with SARS-CoV-2 Omicron BA.2 variant infection:a randomized controlled trial

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World Journal of Pediatrics 2024年第5期20卷 461-469页

作者： Ji-Lei Lin Fen Zhang Yan-Bo Li Shu-Hua Yuan Jin-Hong Wu Jing Zhang Lei Zhang Yi He Jie Chen Yong Yin Department of Respiratory Medicine Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong University1678 Dongfang RoadPudong DistrictShanghaiChina University of British Columbia VancouverCanada Information Technology Department Shanghai Children’s Medical Center National Children’s Medical CenterSchool of MedicineShanghai Jiao Tong University1678 Dongfang RoadPudong DistrictShanghaiChina Department of Otorhinolaryngology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong University1678 Dongfang RoadPudong DistrictShanghaiChina Department of Respiratory Medicine Sanya Women and Children’s Hospital Affiliated to Hainan Medical CollegeHainan Branch of Shanghai Children’s Medical CenterSanyaChina Department of Respiratory Medicine Linyi Maternal and Child Healthcare HospitalLinyiChina Shanghai Children’s Medical Center Pediatric Medical Complex(pudong) ShanghaiChina Pediatric AI Clinical Application and Research Center Shanghai Children’s Medical CenterShanghaiChina

Background Saline nasal irrigation is an effective therapy for relieving common cold *** study aimed to investigate and explore the efficacy of physiological seawater nasal irrigation(PSNI)on children with mild and asymptomatic infection with *** This randomized controlled trial was conducted in Shanghai,China,and 403 children with mild and asymptomatic infection with Omicron were *** children were allocated into the PSNI group and the control *** primary outcome was the duration of viral shedding(DVS),and the secondary outcome was the change in clinical *** The median age of all participants was 5.59(6.26)years *** DVS was significantly shorter in the PSNI group[2.40(1.13)]than in the control group[3.09(2.14)](P=0.014).The multivariable Cox regression model also showed that patients in the PSNI group had an increased probability of shorter DVS compared with patients in the control group[hazard ratio(HR),1.27;95%confidence interval(CI),1.04–1.55;P=0.017].Subgroup analysis suggested that the DVS of patients without full vaccination was significantly reduced in the PSNI *** proportions of runny nose and stuffy nose were apparently reduced in the first three days in the PSNI group or the control group,but there was no evidence showing that PSNI contributes to the benefit compared with the control *** PSNI can reduce the DVS of patients with mild and asymptomatic infection with SARS-CoV-2 Omicron BA.2 variant.

关键词： Children Duration of viral shedding Omicron Physiological seawater nasal irrigation

Sialyltransferase ST3GAL6 silencing reducesα2,3-sialylated glycans to regulate autophagy by decreasing HSPB8-BAG3 in the brain with hepatic encephalopathy

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 485-498页

作者： Xiaocheng LI Yaqing XIAO Pengfei LI Yayun ZHU Yonghong GUO Huijie BIAN Zheng LI Laboratory for Functional Glycomics College of Life SciencesNorthwest UniversityXi’an 710069China National Translational Science Center for Molecular Medicine Department of Cell BiologyFourth Military Medical UniversityXi’an 710032China Medical Experiment Center Shaanxi University of Chinese MedicineXianyang 712046China The Infectious Disease Department Gongli HospitalPudong New AreaShanghai 200135China

End-stage liver diseases,such as cirrhosis and liver cancer caused by hepatitis B,are often combined with hepatic encephalopathy(HE);ammonia poisoning is posited as one of its main pathogenesis *** is closely related to autophagy,but the molecular mechanism of ammonia’s regulatory effect on autophagy in HE remains *** is an essential form of *** the nervous system,abnormal sialylation affects various physiological processes,such as neural development and synapse ***3β-galactosideα2,3-sialyltransferase 6(ST3GAL6)is one of the significant glycosyltransferases responsible for addingα2,3-linked sialic acid to substrates and generating glycan *** found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction,and the expression levels ofα2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3(LC3)and Beclin-1 were upregulated in ammonia-induced *** findings suggest that ST3GAL6 is related to autophagy in ***,we aimed to determine the regulatory relationship between ST3GAL6 and *** found that silencing ST3GAL6 and blocking or degradingα2,3-sialylated glycans by way of Maackia amurensis lectin-II(MAL-II)and neuraminidase can inhibit *** addition,silencing the expression of ST3GAL6 can downregulate the expression of heat shock proteinβ8(HSPB8)and Bcl2-associated athanogene 3(BAG3).Notably,the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 *** results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.

关键词： Hepatic encephalopathy Hyperammonemia Autophagy ST3β-galactosideα2,3-sialyltransferase 6(ST3GAL6) Heat shock proteinβ8(HSPB8)

Targeted metabolomics study of fatty-acid metabolism in lean metabolic-associated fatty liver disease patients

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World Journal of Gastroenterology 2024年第27期30卷 3290-3303页

作者： Pei-Qi Sun Yi-Fu Yuan Qin Cao Xiao-Yan Chen Yuan-Ye Jiang Wen-Min Dong Li-Li Guo Department of Gastroenterology Putuo HospitalShanghai University of Traditional Chinese MedicineShanghai 200062China Department of Pharmacy Shanghai Pudong HospitalFudan University Pudong Medical CenterShanghai 201399China Central Laboratory Shanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China

BACKGROUND The annual incidence of metabolic-associated fatty liver disease(MAFLD)in China has been increasing and is often overlooked owing to its insidious *** 50%of the patients have a normal weight or are not *** are said to have lean-type MAFLD,and few studies of such patients are *** MAFLD is associated with abnormal lipid metabolism,lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and *** and analyze metabolic ***-Q-Orbitrap/MS content determination was used to determine serum palmitic acid(PA),oleic acid(OA),linoleic acid(LA),and arachidonic acid(AA)levels in lean-type MAFLD *** Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals(P*** levels of PA,OA,LA,and AA were significantly increased compared with healthy *** The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly,yielding 65 identified ***,OA,LA,and AA exhibited the most significant changes,offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.

关键词： Lean-type metabolic-associated fatty liver disease Targeted serum metabolomics Fatty acids Principal component analysis Orthogonal partial least squares-discriminant analysis©The Author(s)2024.Published by Baishideng Publishing Group Inc.All rights reserved.

Development and validation of a nomogram to predict allograft survival after pediatric liver transplantation

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World Journal of Pediatrics 2024年第3期20卷 239-249页

作者： Guang-Xiang Gu Shu-Ting Pan Yi-Chen Fan Chen Chen Qiang Xia Department of Liver Surgery Renji HospitalShanghai Jiaotong University School of MedicineNo.160 Pujian RoadPudong New DistrictShanghai 200128China Department of Liver Transplantation Sun Yet-Sen Memorial HospitalSun Yat-Sen UniversityNo.107 Yanjiang West RoadGuangzhou 510080China Clinical Center for Investigation Renji HospitalShanghai Jiaotong University School of MedicineShanghaiChina Department of Anesthesiology Renji HospitalShanghai Jiaotong University School of MedicineShanghaiChina

Background Liver transplantation is the main treatment for cholestatic liver disease and some metabolic liver diseases in ***,no accurate prediction model to determine the survival probability of grafts prior to surgery *** study aimed to develop an effective prognostic model for allograft survival after pediatric liver *** This retrospective cohort study included 2032 patients who underwent pediatric liver transplantation between January 1,2006,and January 1,2020.A nomogram was developed using Cox regression and validated based on bootstrap *** and discriminatory accuracies were determined using the concordance index and visualized using calibration curves;net benefits were calculated for model *** online Shiny application was developed for easy access to the *** Multivariable analysis demonstrated that preoperative diagnosis,recipient age,body weight,graft type,preoperative total bilirubin,interleukin-1β,portal venous blood flow direction,spleen thickness,and the presence of heart disease and cholangitis were independent factors for survival,all of which were selected in the *** of the nomogram indicated that the 1-,3-,and 5-year predicted survival rates agreed with the actual survival *** concordance indices for graft survival at 1,3,and 5 years were 0.776,0.757,and 0.753,respectively,which were significantly higher than those of the Pediatric End-Stage Liver Disease and Child-Pugh scoring *** allograft dysfunction risk of a recipient could be easily predicted using the following URL:https://***/ASPELT/l Conclusion The allograft survival after pediatric liver transplantation(ASPELT)score model can effectively predict the graft survival rate after liver transplantation in children,providing a simple and convenient evaluation method for clinicians and patients.

关键词： Allograft survival Nomogram Pediatric liver transplantation

BMSC-derived Exosomes Ameliorate Peritoneal Dialysis-associated Peritoneal Fibrosis via the Mir-27a-3p/TP53 Pathway

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Current Medical Science 2024年第2期44卷 333-345页

作者： Jun-li ZHAO Lin ZHAO Qiu-nan ZHAN Miao LIU Ting ZHANG Wen-wen CHU Department of Nephrology Shanghai University of Medicine&Health Sciences Affiliated Zhoupu HospitalShanghai 201318China Orthopedic Department Guangming Traditional Chinese Medicine Hospital of Pudong New AreaShanghai 201399China

Objective:Peritoneal fibrosis(PF)is the main cause of declining efficiency and ultrafiltration failure of the peritoneum,which restricts the long-term application of peritoneal dialysis(PD).This study aimed to investigate the therapeutic effects and mechanisms of bone marrow mesenchymal stem cells-derived exosomes(BMSC-Exos)on PF in response to ***:Small RNA sequencing analysis of BMSC-Exos was performed by second-generation sequencing.C57BL/6J mice were infused with 4.25%glucose-based peritoneal dialysis fluid(PDF)for 6 consecutive weeks to establish a PF model.A total of 36 mice were randomly divided into 6 groups:control group,1.5%PDF group,2.5%PDF group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment *** transcription quantitative polymerase chain reaction(RT-qPCR)was performed to measure the expression level of miR-27a-3p in BMSC-Exos and peritoneum of mice treated with different concentrations of *** and Masson staining were performed to evaluate the extent of *** therapeutic potential of BMSC-Exos for PF was examined through pathological examination,RT-qPCR,Western blotting,and peritoneal function ***-mesenchymal transition(EMT)of HMrSV5 was induced with 4.25%*** were divided into control group,4.25%PDF group,BMSC-Exos treatment group,and BMSC-Exos+TP53 treatment *** Counting Kit-8 assay was used to measure cell viability,and transwell migration assay was used to verify the capacity of BMSC-Exos to inhibit EMT in HMrSV5 ***:Small RNA sequencing analysis showed that miR-27a-3p was highly expressed in BMSC-derived exosomes compared to *** RT-qPCR results showed that the expression of miR-27a-3p was upregulated in BMSC-Exos,but decreased in PD *** found that PF was glucose concentration-dependently enhanced in the peritoneum of the PD *** with the control mice,the PD mice showed high solute transport and decreased ultrafiltration volume as well as an obvious f

关键词： peritoneal fibrosis bone marrow mesenchymal stem cell-derived exosomes miR-27a-3p TP53 epithelialmesenchymal transition

Delivery room resuscitation intensity and associated neonatal outcomes of 24^(+0)-31^(+6) weeks'preterm infants in China:a retrospective cross-sectional study

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World Journal of Pediatrics 2024年第1期20卷 64-72页

作者： Si-Lu Wang Chun Chen Xin-Yue Gu Zhao-Qing Yin Le Su Si-Yuan Jiang Yun Cao Li-Zhong Du Jian-Hua Sun Jiang-Qin Liu Chuan-Zhong Yang Department of Neonatology Shanghai Key Laboratory of Maternal Fetal MedicineShanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyShanghai First Maternity and Infant HospitalSchool of MedicineTongji UniversityNo.2699Gaoke Western RoadPudong DistrictShanghai 201204China Department of Neonatology Affiliated Shenzhen Maternity and Child Healthcare HospitalSouthern Medical UniversityNo.2004Hongli RoadFutian DistrictShenzhen 518028China NHC Key Laboratory of Neonatal Diseases Fudan UniversityChildren's Hospital of Fudan UniversityShanghaiChina Department of Neonatology People's Hospital of DehongKunming Medical UniversityDehongChina Department of Neonatology Children's Hospital of Fudan UniversityShanghaiChina Department of Neonatology Children's HospitalZhejiang University School of MedicineHangzhouChina Department of Neonatology Shanghai Children's Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background The aim of this study was to review current delivery room(DR)resuscitation intensity in Chinese tertiary neonatal intensive care units and to investigate the association between DR resuscitation intensity and short-term outcomes in preterm infants born at 24+0_31+6 weeks gestation age(GA).Methods This was a retrospective cross-sectional *** source population was infants born at 24+0_31+6 weeks'GA who were enrolled in the Chinese Neonatal Network 2019 *** infants were categorized into five groups:(1)regular care;(2)oxygen supplementation and/or continuous positive airway pressure(O2/CPAP);(3)mask ventilation;(4)endotracheal intubation;and(5)cardiopulmonary resuscitation(CPR).The association between DR resuscitation and shortterm outcomes was evaluated by inverse propensity score-weighted logistic *** Of 7939 infants included in this cohort,2419(30.5%)received regular care,1994(25.1%)received O,/CPAP,1436(18.1%)received mask ventilation,1769(22.3%)received endotracheal intubation,and 321(4.0%)received CPR in the *** maternal age and maternal hypertension correlated with a higher need for resuscitation,and antenatal steroid use tended to be associated with a lower need for resuscitation(P<0.001).Severe brain impairment increased significantly with increasing amounts of resuscitation in DR after adjusting for perinatal *** strategies vary widely between centers,with over 50%of preterm infants in eight centers requiring higher intensity *** Increased intensity of DR interventions was associated with increased mortality and morbidities in very preterm infants in *** is wide variation in resuscitative approaches across delivery centers,and ongoing quality improvement to standardize resuscitation practices is needed.

关键词： Cardiopulmonary resuscitation Delivery room Endotracheal intubation Neonatal resuscitation Preterm

Biomimetic Phosphohydrolase Nanozyme Based on DefectEngineered Metal-Organic Framework

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CCS Chemistry 2024年第7期6卷 1821-1835页

作者： Xiaoxue Kou Yuhong Lin Yong Shen Linjing Tong Rui Gao Suya Liu Siming Huang Fang Zhu Guosheng Chen Gangfeng Ouyang MOE Key Laboratory of Bioinorganic and Synthetic Chemistry School of ChemistrySun Yat-sen UniversityGuangzhou 510006 Shanghai NanoPort Thermo Fisher ScientificPudong DistrictShanghai 200120 Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical Pharmacology The NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and The Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436

Phosphodiester bonds are the backbone linkages of all the nucleic acids which store and transfer biological *** hydrolysis of phosphodiester bonds is of great importance to the replication,recombination,and damage repair of DNA as well as the maturation and processing of ***,the spontaneous scission of individual phosphodiester linkages is kinetically challenging under physiological conditions,with an estimated half-life of 30 million ***,we discover a defect-engineered Zr-metal-organic framework(Zr-MOF)nanozyme containing cluster-missing reo defects,named UiO-66 REO,that possesses intrinsic phosphodiesterase-like activity that allows for the cleavage of the phosphodiester bond in physiological condition(pH=7.4 and 37℃),outperforming the activityrecording *** atomic-level structure of the UiO-66 REO nanozyme has been directly identified by the synchrotron radiation absorption spectrum and integrated differential phase contrast-scanning transmission electron *** find that both the defective boundary regions and unusual Zr6-clusters formed in the reo phase of the UiO-66 REO nanozyme contribute to the improvement in efficiency of phosphodiesterase-like hydrolysis,which realizes the cleavage of DNA in mild *** work offers a new insight into biomimetic enzymology using crystal and defect engineering and opens up new possibilities for the development of low-cost,structurally stable and sustainable phosphodiesterase nanozymes for different biological applications.

关键词： nanozyme metal-organic framework biomimetic catalysis hydrolase-like activity defective engineering

Correlation between cerebral neurotransmitters levels by proton magnetic resonance spectroscopy and HbA1c in patients with type 2 diabetes

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World Journal of Diabetes 2024年第6期15卷 1263-1271页

作者： Xiang-Yu Gao Chen-Xia Zhou Hong-Mei Li Min Cheng Da Chen Zi-Yi Li Bo Feng Jun Song Department of Endocrinology East HospitalTongji University School of MedicineShanghai 200120China Department of Endocrinology Qilu Hospital(Qingdao)Cheeloo College of MedicineShandong UniversityQingdao 266000Shandong ProvinceChina Department of Immunization Program Huangdao District Center for Disease Prevention and ControlQingdao 266400Shandong ProvinceChina

BACKGROUND Cognitive dysfunction is the main manifestation of central *** cognitive impairments tend to be overlooked in patients with diabetes mellitus(DM),there is a growing body of evidence linking DM to cognitive *** is closely related to neurological abnormalities,while often disregarded in clinical *** in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM(T2DM).AIM To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c(HbA1c)*** A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East *** participants were divided into four groups according to their HbA1c levels using the interquartile method,namely Q1(<7.875%),Q2(7.875%-9.050%),Q3(9.050%-11.200%)and Q4(≥11.200%).Clinical data were collected and measured,including age,height,weight,neck/waist/hip circumferences,blood pressure,comorbidities,duration of DM,and biochemical ***,neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance *** The HbA1c level was significantly associated with urinary microalbumin(mALB),triglyceride,low-density lipoprotein cholesterol(LDL-C),homeostasis model assessment of insulin resistance(HOMA-IR),and beta cell function(HOMA-β),N-acetylaspartate/creatine(NAA/Cr),and NAA/choline(NAA/Cho).Spearman correlation analysis showed that mALB,LDL-C,HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c(P<0.05),whereas HOMA-βwas negatively correlated with the HbA1c level(P<0.05).Ordered multiple logistic regression analysis showed that NAA/Cho[Odds ratio(OR):1.608,95%confidence interval(95%CI):1.004-2.578,P<0.05],LDL-C(OR:1.627,95%CI:1.119-2.370,P<0.05),and HOMA-IR(OR:1.107,95%CI:1.031-

关键词： Type 2 diabetes mellitus Hemoglobin A1c Proton magnetic resonance spectroscopy Neurotransmitters Central neuropathy