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EGFR-targeted and gemcitabine-incorporated chemogene for combinatorial pancreatic cancer treatment

Nano Research 2024年第2期17卷 848-857页

作者： Miao xie Qiushuang Zhang Yuanyuan Guo Lijuan Zhu xinyuan Zhu Chuan Zhang school of Chemistry and Chemical Engineering Frontiers Science Center for Transformative MoleculesInstitute of Molecular MedicineSixth people’s HospitalSchool of MedicineShanghai Key Laboratory for Molecular Engineering of Chiral DrugsShanghai Jiao Tong UniversityShanghai 200240China Department of Radiology Shanghai Jiao Tong University Affiliated Sixth People’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200233China Institute of Molecular medicine Shanghai Jiao Tong University Affiliated Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China

Pancreatic cancer stands out as a recognized intractable tumor due to its high malignancy and mortality rates,which are largely attributed to the insensitivity of current clinical chemotherapies or *** chemo and gene therapy that integrates different therapeutic targets,may increase the chemosensitivity of pancreatic cancer and synergistically enhance the antitumor ***,conventional co-delivery of gene and chemo drugs is intensively dependent on complex nanoparticle delivery systems,thus would be limited by unstable drug packaging,nonspecific biodistribution,and biosafety ***,we rationally designed an epidermal growth factor-receptor(EGFR)-targeted and gemcitabine-incorporated oligonucleotide(termed as chemogene)with anti-Bcl-2 sequence,which achieves simple and precise integration of gemcitabine into a gene regulative agent,as well as the EGFR-targeted delivery for pancreatic cancer *** solid-phase synthesis,gemcitabine,as the first-line chemodrug for pancreatic cancer,is introduced to the antisense oligonucleotide to replace all cytosine nucleosides to obtain the gemcitabine-integrated chemogene(Ge-ASO^(Bcl-2)).Thereafter,Ge-ASO^(Bcl-2)is covalently coupled with EGFR nanobody to construct the final targeted chemogene without any exogenous ***,this nanobody-conjugated chemogene exhibits remarkable tumor targeting capability and antitumor effects both in vitro and in vivo,which initiates a first step toward the application of combinatorial chemo and gene therapy for future pancreatic cancer treatment.

关键词： antisense oligonucleotide chemogene nanobody drug delivery system pancreatic cancer

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Endorepellin downregulation promotes angiogenesis after experimental traumatic brain injury

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Neural Regeneration Research 2024年第5期19卷 1092-1097页

作者： Qian Zhang Yao Jing Qiuyuan Gong Lin Cai Ren Wang Dianxu Yang Liping Wang Meijie Qu Hao Chen Yaohui Tang Hengli Tian Jun Ding Zhiming Xu Department of Gerontology Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurosurgery Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurology Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina school of Biomedical Engineering and Med-X Research Institute Shanghai Jiao Tong UniversityShanghaiChina Department of Neurology Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina

Endorepellin plays a key role in the regulation of angiogenesis,but its effects on angiogenesis after traumatic brain injury are *** study explored the effects of endorepellin on angiogenesis and neurobehavioral outcomes after traumatic brain injury in *** were randomly divided into four groups:sham,controlled cortical impact only,adeno-associated virus(AAV)-green fluorescent protein,and AAV-shEndorepellin-green fluorescent protein *** the controlled cortical impact model,the transduction of AAV-shEndorepellin-green fluorescent protein downregulated endorepellin while increasing the number of CD31+/Ki-67+proliferating endothelial cells and the functional microvessel density in mouse *** changes resulted in improved neurological function compared with controlled cortical impact *** blotting revealed increased expression of vascular endothelial growth factor and angiopoietin-1 in mice treated with AAV-shEndorepellin-green fluorescent *** radiation angiography showed that endorepellin downregulation promoted angiogenesis and increased cortical neovascularization,which may further improve neurobehavioral ***,an in vitro study showed that downregulation of endorepellin increased tube formation by human umbilical vein endothelial cells compared with a *** analysis found that endorepellin downregulation may mediate angiogenesis by activating vascular endothelial growth factor-and angiopoietin-1-related signaling pathways.

关键词： angiogenesis controlled cortical impact endorepellin neurological function traumatic brain injury

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Pipeline of New Drug Treatment for Non-alcoholic Fatty Liver Disease/Metabolic Dysfunction-associated Steatotic Liver Disease

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Journal of Clinical and Translational Hepatology 2024年第9期12卷 802-814页

作者： Ye Hu Chao Sun Ying Chen Yu-Dong Liu Jian-Gao Fan Department of Gastroenterology Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Geriatrics Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Gastroenterology Changxing branch of Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina

Given the global prevalence and rising incidence of metabolic dysfunction-associated steatotic liver disease(MASLD),the absence of licensed medications is striking.A deeper understanding of the heterogeneous nature of MASLD has recently contributed to the discovery of novel groups of agents and the potential repurposing of currently available *** therapies center on four major *** the close relationship between MASLD and type 2 diabetes,the first approach involves antidiabetic medications,including incretins,thiazolidinedione insulin sensitizers,and sodium-glucose cotransporter 2 *** second approach targets hepatic lipid accumulation and the resultant metabolic *** in this group include peroxisome proliferatoractivated receptor agonists(e.g.,pioglitazone,elafibranor,saroglitazar),bile acid-farnesoid X receptor axis regulators(obeticholic acid),de novo lipogenesis inhibitors(aramchol,NDI-010976),and fibroblast growth factor 21/19 *** third approach focuses on targeting oxidative stress,inflammation,and *** in this group include antioxi-dants(vitamin E),tumor necrosis factor a pathway regulators(emricasan,pentoxifylline,ZSP1601),and immune modulators(cenicriviroc,belapectin).The final group targets the gut(IMM-124e,solithromycin).Combination therapies targeting different pathogenetic pathways may provide an alternative to MASLD treatment with higher efficacy and fewer side *** review aimed to provide an update on these medications.

关键词： NAFLD MASLD Clinical trial Medication Hypoglycemic agents Intermediary metabolism

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Exosome-encapsulated lncRNA HOTAIRM1 contributes to PM_(2.5)-aggravated COPD airway remodeling by enhancing myofibroblast differentiation

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Science China(Life Sciences) 2024年第5期67卷 970-985页

作者： Huaqi Guo Luo Fei Hengyi Yu Yan Li Yan Feng Shaowei Wu Yan Wang The Ninth People’s hospital of Shanghai jiao tong university school of medicine Shanghai 200011China school of Public Health Shanghai Jiao Tong University School of MedicineShanghai 200020China Department of Occupational and Environmental Health Sciences School of Public HealthXi’an Jiao Tong University Health Science CenterXi’an 710049China

Emphysema,myofibroblast accumulation and airway remodeling can occur in the lungs due to exposure to atmospheric pollution,especially fine particulate matter(PM_(2.5)),leading to chronic obstructive pulmonary disease(COPD).Specifically,bronchial epithelium-fibroblast communication participates in airway remodeling,which results in *** increasing number of studies are now being conducted on the role of exosome-mediated cell-cell communication in disease ***,we investigated whether exosomes generated from bronchial epithelial cells could deliver information to normal stromal fibroblasts and provoke cellular responses,resulting in airway obstruction in *** studied the mechanism of exosome-mediated intercellular communication between human bronchial epithelial(HBE) cells and primary lung fibroblasts(pLFs).We found that PM_(2.5)-induced HBE-derived exosomes promoted myofibroblast differentiation in ***,the exosomal lncRNA expression profiles derived from PM_(2.5)-treated HBE cells and nontreated HBE cells were investigated using an Agilent Human LncRNA *** coculture assays and direct exosome treatment,we found that HBE cell-derived exosomal HOTAIRM1 facilitated the myofibroblast differentiation of ***,we discovered that exosomal HOTAIRM1 enhanced p LF proliferation to secrete excessive collagen secretion,leading to airway obstruction by stimulating the TGF-β/SMAD3 signaling ***,PM_(2.5)reduced FEV1/FVC and FEV1 and increased the level of serum exosomal HOTAIRM1 in healthy people;moreover,serum exosomal HOTAIRM1 was associated with PM_(2.5)-related reductions in FEV1/FVC and *** findings show that PM_(2.5)triggers alterations in exosome components and clarify that one of the paracrine mediators of myofibroblast differentiation is bronchial epithelial cell-derived HOTAIRM1,which has the potential to be an effective prevention and therapeutic target for PM_(2.5)-induced COPD.

关键词： PM2.5 exosomal lncRNAs HOTAIRM1 chronic obstructive pulmonary disease

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Decitabine induces IRF7-mediated immune responses in p53-mutated triple-negative breast cancer:a clinical and translational study

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Frontiers of medicine 2024年第2期18卷 357-374页

作者： Haoyu Wang Zhengyuan Wang Zheng Wang xiaoyang Li Yuntong Li Ni Yan Lili Wu Ying Liang Jiale Wu Huaxin Song Qing Qu Jiahui Huang Chunkang Chang Kunwei Shen xiaosong Chen Min Lu Department of General Surgery Comprehensive Breast Health CenterRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine(Shanghai)Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Shanghai Institute of HematologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai200025China

p53 is mutated in half of cancer ***,no p53-targeting drugs have been ***,we reposition decitabine for triple-negative breast cancer(TNBC),a subtype with frequent p53 mutations and extremely poor *** a retrospective study on tissue microarrays with 132 TNBC cases,DNMT1 overexpression was associated with p53 mutations(P=0.037)and poor overall survival(OS)(P=0.010).In a prospective DEciTabinE and Carboplatin in TNBC(DETECT)trial(NCT03295552),decitabine with carboplatin produced an objective response rate(ORR)of 42%in 12 patients with stage IV *** the 9 trialed patients with available TP53 sequencing results,the 6 patients with p53 mutations had higher ORR(3/6 vs.0/3)and better OS(16.0 vs.4.0 months)than the patients with wild-type *** a mechanistic study,isogenic TNBC cell lines harboring DETECT-derived p53 mutations exhibited higher DNMT1 expression and decitabine sensitivity than the cell line with wild-type *** the DETECT trial,decitabine induced strong immune responses featuring the striking upregulation of the innate immune player IRF7 in the p53-mutated TNBC cell line(upregulation by 16-fold)and the most responsive patient with *** integrative studies reveal the potential of repurposing decitabine for the treatment of p53-mutated TNBC and suggest IRF7 as a potential biomarker for decitabine-based treatments.

关键词： p53 mutation triple-negative breast cancer decitabine DNMT1 IRF7 innate immune response

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A pilot study on Paxlovid therapy for hemodialysis patients with severe acute respiratory syndrome coronavirus 2 infections

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Frontiers of medicine 2024年第1期18卷 169-179页

作者： Xu Hao Zhiyao Bao Ranran Dai xiaojing Wu xin Li Muyin Zhang Hao Li Lili Xu Panpan Qiao Xuefei Liu Weiting Hu Ze Zhang Jie Fang Min Zhou Weiming Wang Jieming Qu Department of Nephrology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Department of Pulmonary and Critical Care medicine Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Institute of Respiratory Diseases Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Pharmacy Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China

We aimed to investigate the safety and efficacy of nirmatrelvir/ritonavir(Paxlovid)therapy for hemodialysis-dependent patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** hemodialysis patients infected with the Omicron variant of SARS-CoV-2 from April 3 to May 30,2022,were *** parameters and chest CT(computed tomography)imaging were *** treatment group included six patients who received 150 mg/100 mg of Paxlovid orally once daily for 5 days,whereas the control group included seven patients who received basic *** serious adverse reactions or safety events were *** control patients progressed to moderate disease,and none in the treatment group showed progression of chest CT findings(P<0.05).Paxlovid therapy tended toward early viral clearance and low viral load on Day ***,83.3%of the patients in the treatment group and 57.1%of the patients in the control group turned negative within 22 *** the Paxlovid treatment group,we found significantly increased levels of lymphocytes(P=0.03)and eosinophils(P=0.02)and decreased levels of D-dimer on Day 8 compared with those on Day *** therapy showed a potential therapeutic effect with good tolerance in hemodialysis *** optimal dose and effectiveness evaluation must be further investigated in a largeer cohort.

关键词： Paxlovid hemodialysis SARS-CoV-2 viral load chest CT scan

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Lipid metabolism-related long noncoding RNAs:A potential prognostic biomarker for hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第33期30卷 3799-3802页

作者： Rui-Nan Zhang Jian-Gao Fan Department of Gastroenterology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China

The incidence rates of hepatocellular carcinoma(HCC)have increased in recent *** advancements in therapy and early diagnosis improving shortterm prognosis,long-term outcomes remain *** noncoding RNAs(lncRNAs)and lipid metabolism play crucial roles in the development and progression of *** lipid synthesis promotes HCC progression,and lncRNAs can reprogram the expression of lipogenic ***,lipid metabolism-related(LMR)-lncRNAs regulate lipid anabolism,accelerating the onset and progression of *** suggests that LMR-lncRNAs could serve as novel prognostic biomarkers and therapeutic targets.

关键词： Long noncoding RNAs Lipid metabolism Hepatocellular carcinoma Prognosis Biomarker

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Risk evaluation for diabetic retinopathy in Chinese renalbiopsied type 2 diabetes mellitus patients

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1283-1291页

作者： Shou-Yue Huang Qi-Wei Hu Ze-Wei Zhang Ping-Yan Shen Qiong Zhang Department of Ophthalmology Ruijin Hospital Affiliated Medical SchoolShanghai Jiao Tong UniversityShanghai 200025China Department of Nephrology Ruijin Hospital Affiliated Medical SchoolShanghai Jiao Tong UniversityShanghai 200025China

AIM:To investigate diabetic retinopathy(DR)prevalence in Chinese renal-biopsied type 2 diabetes mellitus(T2DM)patients with kidney dysfunction,and to further evaluate its relationship with diabetic nephropathy(DN)incidence and the risk factors for DR development in this ***:A total of 84 renal-biopsied T2DM patients were *** and imaging examinations were employed for DR *** information and clinical measures along with renal histopathology were analyzed for comparisons between the DR and non-DR *** factors on DR development were analyzed with multiple logistic ***:DR prevalence was 50%in *** incidences of DN,non-diabetic renal disease(NDRD)and mixed-type pathology were 47.6%,19.0%and 33.3%in the DR group respectively,while 11.9%,83.3%and 4.8%in the non-DR *** blood pressure,ratio of urinary albumin to creatine ratio,urinary albumin,24-hours urinary protein,the incidence and severity of DN histopathology were found statistically increased in the DR *** logistic regression analysis showed histopathological DN incidence significantly increased the risk of DR development[odds ratio(OR)=21.664,95%confidential interval(CI)5.588 to 83.991,P<0.001 for DN,and OR=45.475,95%CI 6.949 to 297.611,P<0.001 for mixed-type,respectively,in reference to (NDRD)],wherein DN severity positively ***:Renal histopathological evidence indicates DN incidence and severity increases the risk of DR development in Chinese T2DM patients inexperienced of regular fundus examinations.

关键词： diabetic retinopathy diabetic nephropathy vision threatens renal biopsy vision screening

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Mitochondria-targeted nanoparticles overcome chemoresistance via downregulating BACH1/CD47 axis in ovarian carcinoma

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Chinese Chemical Letters 2024年第5期35卷 344-350页

作者： Ke Gong Jinghan Liao Jiangtao Lin Quan Wang Zhihua Wu Liting Wang Jiali Zhang Yi Dong Yourong Duan Jianhua Chen State Key Laboratory of Systems medicine for Cancer Shanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200032China Department of Ultrasound Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China Department of Oncology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China

The platinum-based chemotherapy is a routine strategy for the treatment of ovarian cancer,while it is prone to chemoresistance in clinical,which hinders the ***,it is urgently needed to elucidate the underlying mechanism of drug resistance and form the appropriate *** sequencing results showed that cisplatin(DDP)resistant ovarian cancer overexpressed BTB and CNC homology 1(BACH1),and up-regulated the“don’t eat me”signal *** identified that hemin,a BACH1 inhibitor,could effectively down-regulate BACH1 and simultaneously inhibit ***,hemin has a synergistic effect with *** designed a pH-responsive nanoparticle(H/D@FA-CaP-NPs)in which folic acid(FA)ensured targeting of ovarian cancer cells,while hemin inhibited BACH1 as well as down-regulated CD47,achieving the promotion of apoptosis of tumor cells and inducing phagocytosis of tumors by ***,hemin has a synergistic effect with DDP to promote apoptosis of tumor ***,hemin and DDP was encapsulated within hydrophobic 1,2-distearoyl-sn-glycero-3-phosphoethanolamine(DSPE)to form a tight core,and hydrophilic polyethylene glycol 2000(PEG2000)and calcium phosphate(CaP)formed the outside shell,and FA was modified on the surface of *** terms of function,(a)FA enhanced the active targeting of nanoparticles to tumors;(b)NPs targeted mitochondria to induce reactive oxygen species(ROS)production;(c)hemin encapsulated in nanoparticles could specifically target BACH1,thereby down regulating CD47;(d)hemin had a synergistic effect with DDP,thus augmenting the ***,mitochondria-targeted nanoparticles H/D@FA-CaP-NPs promoted tumor apoptosis and mobilized phagocytosis to treat tumor,providing a novel scheme for clinical treatment of cisplatin-resistant ovarian carcinoma.

关键词： Cisplatin-resistant Hemin BACH1 CD47 Phagocytosis ROS Synergistic effect

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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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