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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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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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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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Cellular strategies to induce immune tolerance after liver transplantation:Clinical perspectives

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World Journal of gastroenterology 2024年第13期30卷 1791-1800页

作者： Ai-Wei Zhou Jing Jin Yuan Liu department of Liver Surgery Renji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China department of Nursing Renji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China department of Liver Transplantation Shanghai Immune Therapy InstituteShanghai 200127China

Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative ***,long-term side-effects of immunosuppressants,like infection,metabolic disorders and malignant tumor are gaining more *** tolerance is the status in which LT recipients no longer need to take any immunosuppressants,but the liver function and intrahepatic histology maintain *** approaches to achieve immune tolerance after transplantation include spontaneous,operational and induced *** first two means require no specific intervention but withdrawing immunosuppressant gradually during *** clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after *** the understanding to the underlying mechanisms of immune tolerance,many strategies have been developed to induce tolerance in LT *** strategy is one of the most promising methods for immune tolerance induction,including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune *** safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials,while obstacles still exist before translating into clinical ***,we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.

关键词： Cellular therapy Induced tolerance Liver transplantation Regulatory T cells Regulatory dendritic cells

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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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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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Topological reorganization and functional alteration of distinct genomic components in gallbladder cancer

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Frontiers of medicine 2024年第1期18卷 109-127页

作者： Guoqiang Li Peng Pu Mengqiao Pan Xiaoling Weng Shimei Qiu Yiming Li Sk Jahir Abbas Lu Zou Ke Liu Zheng Wang Ziyu Shao Lin Jiang Wenguang Wu Yun Liu Rong Shao Fatao Liu Yingbin Liu department of Biliary-Pancreatic Surgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteShanghai200127China shanghai Key Laboratory of Biliary Tract disease Shanghai200082China department of Health Science and Engineering University of Shanghai for Science and TechnologyShanghai200082China shanghai Tenth People’s hospital of tongji university Shanghai200072China department of General Surgery Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200082China department of Pharmacology Shanghai Jiao Tong University School of MedicineShanghai200025China

Altered three-dimensional architecture of chromatin influences various genomic regulators and subsequent gene expression in human ***,knowledge of the topological rearrangement of genomic hierarchical layers in cancer is largely ***,by taking advantage of in situ Hi-C,RNA-sequencing,and chromatin immunoprecipitation sequencing(ChIP-seq),we investigated structural reorganization and functional changes in chromosomal compartments,topologically associated domains(TADs),and CCCTC binding factor(CTCF)-mediated loops in gallbladder cancer(GBC)tissues and cell *** observed that the chromosomal compartment A/B switch was correlated with CTCF binding levels and gene expression *** inter-TAD interactions with weaker TAD boundaries were identified in cancer cell lines relative to normal ***,the chromatin short loops and cancer unique loops associated with chromatin remodeling and epithelial–mesenchymal transition activation were enriched in cancer compared with their control ***-specific enhancer–promoter loops,which contain multiple transcription factor binding motifs,acted as a central element to regulate aberrant gene *** of individual enhancers in each loop anchor that connects with promoters led to the inhibition of their corresponding gene ***,our data offer the landscape of hierarchical layers of cancer genome and functional alterations that contribute to the development of GBC.

关键词： 3D genome cancer TADs loop gene regulation

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Alteration of ascending colon mucosal microbiota in patients after cholecystectomy

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World Journal of Gastrointestinal Surgery 2024年第8期16卷 2436-2450页

作者： Miao-Yan Fan Qiao-Li Jiang Meng-Yan Cui Meng-Qi Zhao Jing-Jing Wang Ying-Ying Lu department of gastroenterology Jiading Branch of Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 201803China shanghai Key Laboratory of Pancreatic diseases Institute of Translational MedicineShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 201620China department of gastroenterology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 201620China

BACKGROUND Cholecystectomy is a successful treatment option for gallstones,although the inci-dence of colorectal cancer(CRC)has notably increased in post-cholecystectomy(PC)***,it remains uncertain whether the altered mucosal micro-biota in the ascending colon is *** total,30 PC patients and 28 healthy controls underwent colonoscopies to collect mucosal biopsy *** patients were divided based on their clinical ***,16S-rRNA gene sequencing was used to analyze the amplicon,alpha diversity,beta diversity,and composition of the bacterial ***-tionally,the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States(PICRUSt)database,sourced from the Kyoto Encyclopedia of Genes and Genomes,was used to predict the functional capabilities of the *** PC patients were comparable with healthy ***,PC patients older than 60 years had a distinct composition compared to those under 60 years *** richness was considerably higher at the phylum level in PC ***,Parabacteroides,and Bilophila were more abundant in the PC group than in the control ***,PC patients exhibited greater enrichment in metabolic pathways,specifically those related to lipopolysaccharide biosynthesis and vancomycin group antibiotic production,than *** This study indicated that the mucosal microbiota in PC patients was altered,perhaps offering new perspectives on the treatment possibilities for CRC and diarrhea following cholecystectomy.

关键词： Post-cholecystectomy Ascending colon Mucosal Microbiota Colorectal cancer Diarrhea

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Lipid nanovehicles overcome barriers to systemic RNA delivery: Lipid components, fabrication methods, and rational design

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Acta Pharmaceutica Sinica B 2024年第2期14卷 579-601页

作者： Jing Yan Hao Zhang Guangfeng Li Jiacan Su Yan Wei Can Xu institute of Translational medicine Shanghai UniversityShanghai 200444China institute of medicine Shanghai UniversityShanghai 200444China department of Orthopedics Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China department of Orthopedics Shanghai Zhongye HospitalShanghai 200941China Organoid Research Center Shanghai UniversityShanghai 200444China department of gastroenterology Changhai HospitalShanghai 200433China

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery,as demonstrated by the approval of patisiran for amyloidosis therapy in *** illuminate the unique superiority of lipid nanovehicles in RNA delivery,in this review,we first introduce various RNA therapeutics,describe systemic delivery barriers,and explain the lipid components and methods used for lipid nanovehicle ***,we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA ***,the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also *** objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery,inspiring the development of more high-performance RNA lipid nanovesicles in the future.

关键词： Lipid nanovehicles RNAtherapeutics Barriers to systemicRNA delivery Lipid components Fabricationmethods Lipid nanovehicledesign Extrahepatictissue targeting Organ tropism

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The gut microbiome modulate response to immunotherapy in cancer

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Science China Life Sciences 2024年

作者： Shan-Shan Jiang Zi-Ran Kang Ying-Xuan Chen Jing-Yuan Fang Division of gastroenterology and Hepatology Shanghai Institute of Digestive Disease NHC Key Laboratory of Digestive Diseases State Key Laboratory for Oncogenes and Related Genes Renji Hospital School of Medicine Shanghai Jiao Tong University

Gut microbiota have been reported to play an important role in the occurrence and development of malignant tumors. Currently, clinical studies have identified specific gut microbiota and its metabolites associated with efficacy of immunotherapy in multiple types of *** investigations have elucidated that gut microbiota modulate the antitumor immunity and affect the efficacy of cancer immunotherapy. Certain microbiota and its metabolites may favorably remodel the tumor microenvironment by engaging innate and/or adaptive immune cells. Understanding how the gut microbiome interacts with cancer immunotherapy opens new avenues for improving treatment strategies. Fecal microbial transplants, probiotics, dietary interventions, and other strategies targeting the microbiota have shown promise in preclinical studies to enhance the immunotherapy. Ongoing clinical trials are evaluating these approaches. This review presents the recent advancements in understanding the dynamic interplay among the host immunity, the microbiome, and cancer immunotherapy, as well as strategies for modulating the microbiome, with a view to translating into clinical applications.

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