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Glycolytic potential enhanced by blockade of pyruvate influx into mitochondria sensitizes prostate cancer to detection and radiotherapy

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Cancer Biology & medicine 2022年第9期19卷 1315-1333页

作者： Huan Xu Junyi Chen Zhi Cao Xi Chen Caihong Huang Jin Ji Yalong Xu Junfeng Jiang Yue Wang Guowang Xu Lina Zhou Jingyi He Xuedong Wei Jason Boyang Wu Zhong Wang Shancheng Ren Fubo Wang Department of Urology Shanghai Changhai HospitalSecond Military Medical UniversityShanghai 200433China Department of Urology Shanghai Ninth People’s HospitalShanghai 200011China Department of Urology the Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000China Department of Urology No.971 Hospital of the People’s Liberation Army NavyQingdao 266000China Center for Genomic and personalized medicine Guangxi Key Laboratory for Genomic and Personalized MedicineGuangxi Collaborative Innovation Center for Genomic and Personalized MedicineGuangxi Medical UniversityNanning 530021China Research Center of Developmental Biology Second Military Medical UniversityShanghai 200433China Dalian Institute of Chemical Physics Chinese Academy of SciencesDalian 116023China Department of Urology the First Affiliated Hospital of Soochow UniversitySuzhou 215006China Department of Pharmaceutical Sciences College of Pharmacy and Pharmaceutical SciencesWashington State UniversitySpokaneWA 99202USA

Objective:This study aimed to evaluate the effects of mitochondrial pyruvate carrier(MPC)blockade on the sensitivity of detection and radiotherapy of prostate cancer(PCa).Methods:We investigated glycolysis reprogramming and MPC changes in patients with PCa by using metabolic profiling,RNASeq,and tissue *** blockade of pyruvate influx into mitochondria was observed in cellular studies to detect its different effects on prostate carcinoma cells and benign prostate *** mouse models were injected with an MPC inhibitor to evaluate the sensitivity of 18F-fluorodeoxyglucose positron emission tomography with computed tomography and radiotherapy of ***,the molecular mechanism of this different effect of transient blockage towards benign prostate cells and prostate cancer cells was studied in ***:MPC was elevated in PCa tissue compared with benign prostate tissue,but decreased during cancer *** transient blockade increased PCa cell proliferation while decreasing benign prostate cell proliferation,thus increasing the sensitivity of PCa cells to 18F-PET/CT(SUVavg,P=0.016;SUVmax,P=0.03)and radiotherapy(P<0.01).This differential effect of MPC on PCa and benign prostate cells was dependent on regulation by a VDAC1-MPC-mitochondrial homeostasis-glycolysis ***:Blockade of pyruvate influx into mitochondria increased glycolysis levels in PCa but not in non-carcinoma prostate *** transient blockage sensitized PCa to both detection and radiotherapy,thus indicating that glycolytic potential is a novel mechanism underlying PCa *** change in the mitochondrial pyruvate influx caused by transient MPC blockade provides a critical target for PCa diagnosis and treatment.

关键词： Glycolytic potential prostate cancer mitochondrial pyruvate carrier(MPC) mitochondria pyruvate influx diagnosis radiotherapy

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LncRNA SNHG16 promotes colorectal cancer proliferation by regulating ABCB1 expression through sponging miR-214-3p

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The Journal of Biomedical Research 2022年第4期36卷 231-241页

作者： Pei Tan Mu Xu Junjie Nie Jian Qin Xiangxiang Liu Huiling Sun Shukui Wang Yuqin Pan General Clinical Research Center Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu 210006China Department of laboratory medicine Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu 210006China School of medicine Southeast UniversityNanjingJiangsu 210009China Jiangsu Collaborative Innovation Center on Cancer personalized medicine Nanjing Medical UniversityNanjingJiangsu 211100China

Mounting evidence indicates that long non-coding RNAs(lncRNAs)have critical roles in colorectal cancer(CRC)progression,providing many potential diagnostic biomarkers,prognostic biomarkers,and treatment ***,we sought to investigate the role and underlying regulatory mechanism of lncRNA small nucleolar RNA host gene 16(SNHG16)in *** expressions of SNHG16 in CRC were identified by RNA-sequencing and quantitative reverse transcription *** functions of SNHG16 were explored by a series of in vitro and in vivo assays(colony formation assay,flow cytometry assay,and xenograft model).Bioinformatics analysis,RNA fluorescence in situ hybridization and luciferase reporter assay were used to investigate the regulatory mechanism of effects of ***16 was found to be significantly elevated in human CRC tissues and cell *** studies suggested that SNHG16 promoted CRC cell growth both in vitro and in ***,we identified that SNHG16 is expressed predominantly in the ***16 could interact with miR-214-3p and up-regulated its target *** study indicated that SNHG16 plays an oncogenic role in CRC,suggesting it could be a novel biomarker and therapeutic target in CRC.

关键词： SNHG16 ATP-binding cassette subfamily B member 1 microRNA colorectal cancer ceRNA

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Advanced subunit vaccine delivery technologies: From vaccine cascade obstacles to design strategies

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Acta Pharmaceutica Sinica B 2023年第8期13卷 3321-3338页

作者： Yingying Hou Min Chen Yuan Bian Xi Zheng Rongsheng Tong Xun Sun Department of Pharmacy Sichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610072China personalized Drug Therapy Key laboratory of Sichuan Province School of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610072China Key laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China

Designing and manufacturing safe and effective vaccines is a crucial challenge for human health *** on adjuvant-based subunit vaccines is increasingly being explored to meet clinical ***,the adaptive immune responses of subunit vaccines are still unfavorable,which may partially be attributed to the immune cascade obstacles and unsatisfactory vaccine *** extended understanding of the crosstalk between vaccine delivery strategies and immunological mechanisms could provide scientific insight to optimize antigen delivery and improve vaccination *** this review,we summarized the advanced subunit vaccine delivery technologies from the perspective of vaccine cascade obstacles after *** engineered subunit vaccines with lymph node and specific cell targeting ability,antigen cross-presentation,T cell activation properties,and tailorable antigen release patterns may achieve effective immune protection with high precision,efficiency,and *** hope this review can provide rational design principles and inspire the exploitation of future subunit vaccines.

关键词： Subunitvaccine Vaccinedesign Lymph nodetargeting Dendriticcell subset targeting B cell modulation Antigencross-presentation T cell activation Antigenreleasekinetics

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IL-17 induces NSCLC cell migration and invasion by elevating MMP19 gene transcription and expression through the interaction of p300-dependent STAT3-K631 acetylation and its Y705-phosphorylation

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Oncology Research 2024年第4期32卷 625-641页

作者： WEN GE YA LI YUTING RUAN NINGXIA WU PEI MA TONGPENG XU YONGQIAN SHU YINGWEI WANG WEN QIU CHENHUI ZHAO Department of Immunology Nanjing Medical UniversityNanjing210000China Key laboratory of Immunological Environment and Disease Nanjing Medical UniversityNanjing210000China Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing210000China Jiangsu Key laboratory of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing210000China

The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains *** the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and *** investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to ***,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and ***,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all ***,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.

关键词： NSCLC cell migration and invasion IL-17 p300 STAT3 MMP19 Acetylation and phosphorylation

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Boiogito Increases the Synthesis and Secretion of Adiponectin by Promoting Differentiation in Cultured Human Adipocytes

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Health 2023年第12期15卷 1319-1337页

作者： Yuan Gu Ailing Hu Takuji Yamaguchi Masahiro Tabuchi Yasushi Ikarashi Hiroyuki Kobayashi Department of personalized Kampo medicine Juntendo University Graduate School of Medicine Tokyo Japan

Boiogito (BOT) ameliorates insulin resistance and diabetes in several animal models;however, the underlying mechanisms for these in vivo effects remain unclear. Thiazolidine derivatives, which are peroxisome proliferator-activated receptor γ (PPARγ) agonists for the treatment of type II diabetes, promote adiponectin production by inducing adipocyte differentiation, thereby reducing insulin resistance. This study aimed to evaluate the effect of BOT on adipocyte differentiation using cultured human visceral preadipocytes (HVPAds) compared with the thiazolidine derivative troglitazone (TRG). We investigated the effects of BOT (0.125 - 1 mg/mL) and TRG (10 μM) on the differentiation of adipocytes treated with or without tumor necrosis factor-α (TNF-α: 5 ng/mL). On day 14 of culture, the following adipocyte differentiation marker levels were measured: intracellular lipids, extracellular (i.e., medium) adiponectin, and intracellular differentiation-related genes (PPARγ, CCAAT/enhancer binding protein, adiponectin, differentiation cluster 36, glucose transporter type 4). BOT and TRG increased factors associated with differentiation including lipid, adiponectin, and differentiation-related gene expression levels compared with the controls. The increases in these differentiation markers were inhibited by the PPARγ antagonist GW9662 (20 μM). Furthermore, TNF-α decreased all differentiation marker levels. The decreases in differentiation markers were inhibited by BOT and TRG;however, these inhibitory effects were blocked by GW9662. The results suggest that BOT increases the synthesis and secretion of adiponectin by promoting differentiation similar to TRG. This study is the first to demonstrate that adipocyte differentiation-promoting activity is a mechanism for the beneficial effects of BOT on diabetes and insulin resistance.

关键词： Adipocyte Adiponectin Boiogito Differentiation Troglitazone

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Organoid models of gastrointestinal Neoplasms:Origin,current status and future applications in personalized medicine

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Genes & Diseases 2018年第4期5卷 323-330页

作者： Yi Pan Shuliang Zhao Zhijun Cao Division of Gastroenterology and Hepatology Key Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive Disease145 Middle Shandong RoadShanghai200001China

The in vitro organoid model is a major technological breakthrough that has been established as an important tool in many basic biological and clinical *** near-physiological 3D culture system accurately models various biological processes,including tissue renewal,stem cell/niche functions and tissue responses to drugs,mutations or *** have the potential value of being an accurate model for disease predictions or drug screening applications and to identify the ideal treatment for that *** can be modeled by mutating specific cancer genes in wild-type organoids;and patient-derived organoids provide an important resource in the development of personalized cancer *** from cancer patients could be used to identify the ideal treatment for a specific patient by growing matched healthy and diseased organoids from human cancer patients which additionally enables clinical screens for drug *** could also provide autologous cells ordin the futuredtissue for *** this review,we discuss the current advances,challenges and potential applications of this technique in gastrointestinal neoplasms.

关键词： Gastrointestinal neoplasms Intestinal stem cells Living biobanks personalized medicine Stem cell niches Wnt signaling

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Recent advances in the development of in vitro liver models for hepatotoxicity testing

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Bio-Design and Manufacturing 2021年第4期4卷 717-734页

作者： Siming Lu Jingwei Zhang Sha Lin Danfeng Zheng Yan Shen Jiale Qin Yangyang Li Shuqi Wang Department of laboratory medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China State Key laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalNational Clinical Research Center for Infectious DiseasesZhejiang University School of MedicineHangzhou 310003China Institute of Translational medicine Zhejiang UniversityHangzhou 310029China Key laboratory of Women’s Reproductive Health of Zhejiang Province Women’s HospitalZhejiang University School of MedicineHangzhou 310006China Key laboratory of Tissue Engineering and Regenerative medicine of Zhejiang Province Zhejiang University School of MedicineHangzhou 310027China

Liver injury is a common cause of drug approval withdrawal during drug development,pre-clinical research,and clinical *** not properly treated,patients with severe liver injury can suffer from acute liver failure or even ***,utilization of the convenient in vitro hepatotoxicity assessment model for early detection of drug-induced hepatotoxicity is vital for drug development and safe personalized ***(e.g.,hydrogels,nanofibers,decellularized liver matrix)and bioengineering technologies(e.g.,microarrays,micropatterns,3D printing,and microfluidics)have been applied for in vitro hepatotoxicity assessment *** review summarizes the structure and functions of the liver as well as the components of in vitro hepatotoxicity assessment *** addition,it highlights the latest advances in developing hepatotoxicity models with the ultimate goal of further clinical translation.

关键词： Liver injury Drug toxicity In vitro model 3D culture

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Causal Relationship Between Complement C3,C4,and Nonalcoholic Fatty Liver Disease:Bidirectional Mendelian Randomization Analysis

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Phenomics 2021年第5期1卷 211-221页

作者： Longman Li Lulu Huang Aimin Yang Xiuming Feng Zengnan Mo Haiying Zhang Xiaobo Yang Center for Genomic and personalized medicine Guangxi Key Laboratory for Genomic and Personalized MedicineGuangxi Collaborative Innovation Center for Genomic and Personalized MedicineGuangxi Medical UniversityNanning 530021GuangxiChina Nanhu Zhuxi Community Healthcare Center Qingxiu DistrictNanning 530021GuangxiChina School of Public Health The University of Hong KongHong Kong SAR 999077China Department of Occupational Health and Environmental Health School of Public HealthGuangxi Medical UniversityNanning 530021GuangxiChina Department of Urology Institute of Urology and NephrologyThe First Affiliated Hospital of Guangxi Medical UniversityNanning 530021GuangxiChina Department of Public Health School of MedicineGuangxi University of Science and TechnologyLiuzhou 545006GuangxiChina

The complement system is activated during the development of nonalcoholic fatty liver disease(NAFLD).We aimed to evaluate the causal relationship between serum C3 and C4 levels and *** exclusion criteria,a total of 1600 Chinese Han men from the Fangchenggang Area Male Health and Examination Survey cohort were enrolled in cross-sectional analysis,while 572 participants were included in the longitudinal analysis(average follow-up of 4 years).We performed a bidirectional Mendelian randomization(MR)analysis using two C3-related,eight C4-related and three NAFLD-related gene loci as instrumental variables to evaluate the causal associations between C3,C4,and NAFLD risk in cross-sectional *** SD increase in C3 levels was significantly associated with higher risk of NAFLD(OR=1.65,95%CI 1.40,1.94)in cross-sectional analysis while C4 was not(OR=1.04,95%CI 0.89,1.21).Longitudinal analysis produced similar results(HR_(C3)=1.20,95%CI 1.02,1.42;HR_(C4)=1.10,95%CI 0.94,1.28).In MR analysis,there were no causal relation-ships for genetically determined C3 levels and NAFLD risk using unweighted or weighted GRS_C3(β_(E_unweighted)=−0.019,95%CI−0.019,−0.019,p=0.202;β_(E_weighted)=−0.019,95%CI−0.019,−0.019,p=0.322).Conversely,serum C3 lev-els were significantly effected by the genetically determined NAFLD(β_(E_unweighted)=0.020,95%CI 0.020,0.020,p=0.004;β_(E_weighted)=0.021,95%CI 0.020,0.021,p=0.004).Neither the direction from C4 to NAFLD nor the one from NAFLD to C4 showed significant *** results support that the change in serum C3 levels but not C4 levels might be caused by NAFLD in Chinese Han men.

关键词： Nonalcoholic fatty liver disease C3 C4 Mendelian randomization

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Are preoperative inflammatory and nutritional markers important for the prognosis of patients with peritoneal metastasis of colorectal cancer?

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World Journal of Gastrointestinal Oncology 2024年第11期16卷 4522-4527页

作者： Isabella Sforzin Mitesh Borad Pedro Luiz Serrano Uson Junior Center for personalized medicine Hospital Israelita Albert EinsteinSão Paulo 05652900Brazil Division of Hematology-Oncology Department of MedicineMayo Clinic ArizonaMayo Clinic Cancer CenterPhoenixAZ 85054United States

Colorectal cancer(CRC)is a type of cancer that grows from polypoid lesions developing over the *** has a high incidence of about 1.8 million new cases *** screening and lifestyle modifications have stabilized the rate of CRC in high-income countries,the incidence of early-onset CRC is increasing *** worst prognosis for this cancer is linked to recurrence and metastasis,with peritoneal metastasis occurring in 8%to 20%of *** these cases,treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is ***,this approach is risky and requires careful selection of patients who will truly benefit from *** article will discuss the correlation between nutrition and inflammation in patients with peritoneal metastasis and advanced CRC,emphasizing the importance of nutritional and inflammatory markers for assessing disease ***,we will highlight the main biomarkers in the field.

关键词： Colorectal cancer Peritoneal metastasis Inflammation Nutrition Biomarkers Prognosis

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Erythrocyte membrane encapsulated gambogic acid nanoparticles as a therapeutic for hepatocellular carcinoma

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Chinese Chemical Letters 2023年第1期34卷 251-254页

作者： Ruijie Liu Li He Maoyu Liu Lu Chen Jun Hou Jianyou Shi Lan Bai Affiliated Hospital of Southwest Jiaotong University/Department of Cardiology Chengdu Third People’s HospitalChengdu 610031China Department of Pharmacy Jianyang Chinese Medicine HospitalChengdu 641499China personalized Drug Therapy Key laboratory of Sichuan Province Department of PharmacySichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610072China

Gambogic acid(GA)is a potential clinical anticancer drug that can exert antitumor effects via various molecular ***,GA’s low water solubility,poor stability,short half-life,and unavoidable toxic side effects have significantly hampered its clinical *** membranecoated nanoparticles(RBCM-NPs)improve drug’s physicochemical properties,biocompatibility,and pharmacokinetic behaviors,allowing for long-term drug circulation and passive *** this study,a novel biomimetic drug delivery system(DDS)against hepatocellular carcinoma was prepared by covering RBCM on GPP-NPs(GA-loaded m PEG-PLA NPs)to develop the RBC@*** comparison to RBCM-free nanoparticles and free GA,RBC@GPP-NPs improved the drug’s water solubility,stability,safety,and antitumor activity in *** expect that this bionic nanoparticle composite can expand the clinical applicability of GA and provide a feasible solution for the research and development of GA’s nano-formulation.

关键词： Gambogic acid Erythrocyte membrane Drug delivery systems Biomimetic nanoparticles Hepatocellular carcinoma

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