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Targeting X-linked inhibitor of apoptosis protein inhibits pancreatic cancer cell growth through p-Akt depletion

World Journal of Gastroenterology 2012年第23期18卷 2956-2965页

作者： Chun Jiang Xiao-Ping Yi hong Shen Yi-xiong Li Department of Gynaecology and Obstetrics XiangYa Hospital Central South University Changsha 410008 Hu-nan Province China Department of Radiology Xiang Ya Hospital Central South University Changsha 410008 Hunan Province China Medical Research Center Xiang Ya Hospital Central South University Changsha 410008 Hunan Province China Department of General Surgery Xiang Ya Hospi- tal Central South University Changsha 410008 Hunan Prov- ince China

AIM: To determine whether lentivirus-mediated shRNA targeting the X-linked inhibitor of apoptosis protein (XIAP) gene could be exploited in the treatment of pancreatic cancer. METHODS: human pancreatic cancer cells Panc-1, Mia-paca2, Bxpc-3 and SW1990, infected with lentivirus, were analyzed by real-time polymerase chain reaction (PCR). Western blotting was used to examine XIAP protein levels, survivin and p-Akt to confirm the result of real-time PCR and determine the possible mechanism. The 3-(4,5-cimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) assay was used to measure IC50 to determine chemosensitivity to the chemotherapeutic drugs 5-fluorouracil (5-FU) and gemcitabine. A colony assay, MTT assay and a tumorigenicity experiment were used to study cell proliferation in vitro and in vivo . Caspase-3/7 activity, 4',6-diamidino-2-phenylindole-staining and flow cytometric measurements were used to study apoptosis in SW1990 cells. RESULTS: XIAP proteins were found to be differen- tially expressed among pancreatic cancer cell lines Panc-1, Mia-paca2, Bxpc-3 and SW1990. Data of real-time PCR and Western blotting showed that XIAP was reduced persistently and markedly by lentivirus-mediated shRNA. Downregulation of XIAP by transfection with XIAP shRNA resulted in decreased p-Akt expression. XIAP shRNA also inhibited the growth of pancreatic cancer cells in vitro and in vivo , enhanced drug-induced apoptosis and increased chemosensitivity to 5-FU and gemcitabine. Results also suggest that inhibition of XIAP and subsequent p-Akt depletion may have an anti-tumor effect through attenuating the ability of cancer cells to survive. CONCLUSION: Lentivirus-mediated gene therapy is an attractive strategy in the treatment of pancreatic cancer and justifies the use of lentivirus in pancreatic cancer gene therapy studies.

关键词： Pancreatic cancer Lentivirus-mediatedshRNA X-linked inhibitor of apoptosis protein p-Akt Gene therapy Proliferation Apoptosis

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Generation and Characterization of a Nanobody Against SARS-CoV

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Virologica Sinica 2021年第6期36卷 1484-1491页

作者： Jiang-Fan Li Lei he Yong-Qiang Deng Shu-hui Qi Yue-hong Chen Xiao-Lu Zhang Shi-xiong hu Rui-Wen Fan Guang-Yu Zhao Cheng-Feng Qin State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyAcademy of Military Medical Sciences(AMMS)Beijing 100071China College of Veterinary Medicine Shanxi Agriculture UniversityJinzhong 030801China Research Unit of Discovery and Tracing of Natural Focus Diseases Chinese Academy of Medical SciencesBeijing 100071China

The sudden emergence of severe acute respiratory syndrome coronavirus(SARS-CoV) has caused global panic in 2003,and the risk of SARS-CoV outbreak still exists. However, no specific antiviral drug or vaccine is available;thus, the development of therapeutic antibodies against SARS-CoV is needed. In this study, a nanobody phage-displayed library was constructed from peripheral blood mononuclear cells of alpacas immunized with the recombinant receptor-binding domain(RBD) of SARS-CoV. Four positive clones were selected after four rounds of bio-panning and subjected to recombinant expression in E. coli. Further biological identification demonstrated that one of the nanobodies, S14, showed high affinity to SARS-CoV RBD and potent neutralization activity at the picomole level against SARS-CoV pseudovirus. A competitive inhibition assay showed that S14 blocked the binding of SARS-CoV RBD to either soluble or cell-expressed angiotensinconverting enzyme 2(ACE2). In summary, we developed a novel nanobody targeting SARS-CoV RBD, which might be useful for the development of therapeutics against SARS.

关键词： Severe acute respiratory syndrome coronavirus(SARS-CoV) Receptor-binding domain(RBD) Nanobody Neutralizing antibody

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Solution Properties of Mixed Starch/Chitosan Revealed by Resonance Light Scattering

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Chemical Research in Chinese Universities 2012年第6期28卷 1107-1111页

作者： hu Yong FU xiong CheN Xu-dong Zhong Nan-jing School of Food Science Guangdong Pharmaceutical University Zhongshan 528458 P R. China College of Light Industry and Food Science South China University of Technology Guangzhou 510640 P. R. China School of Chemistry and Chemical Engineering Sun Yat-Sen University Guangzhou 510275 P. R. China

The association behavior of starch and chitosan and the dilute solution properties of the starch/chitosan complex were investigated by means of resonance light scattering（RLS） *** interaction between starch and chiotsan was proved by *** on the results,the appropriate association condition was ***,the solution property of starch/chitosan was affected greatly by external factors such as pH value and metal ionic *** change of pH,which causes the irreversible transition of solution from transparent into murky,provides some important information of partitioning behavior of the complex in *** durative enhancement of RLS intensity for the complex exhibited two inflexions and a plateau in the presence of a certain amount of Fe 3＋.It indicates that Fe 3＋ not only increases the RLS intensity,but also induces the micell-aggregate transition of the complex in ***,the thermodynamic parameters for micell formation process at different temperatures,based on the RLS values,were calculated.

关键词： Starch Chitosan Complex Solution property Resonance light scattering

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Ag_(24)Au cluster decorated mesoporous Co_(3)O_(4)for highly selective and efficient photothermal CO_(2)hydrogenation

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Nano Research 2022年第6期15卷 4965-4972页

作者： Yan xiong Xu Liu Yi hu dong Gu Minghang Jiang zuoxiu Tie Zhong Jin MOE Key Laboratory of Mesoscopic Chemistry MOE Key Laboratory of High Performance Polymer Materials and TechnologyJiangsu Key Laboratory of Advanced Organic MaterialsSchool of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China Suzhou Tierui New Energy Technology Co.Ltd. Suzhou 215228China The Institute for Advanced Studies Wuhan UniversityWuhan 430072China

Photothermal carbon dioxide hydrogenation represents a promising route to reduce the emission of greenhouse gas CO_(2)and produce value-added chemicals,but the selectivity and stability of photothermal catalysts need to be ***,we report the rational fabrication of well-defined Ag_(24)Au cluster decorated highly ordered nanorod-like mesoporous Co_(3)O_(4)(Ag_(24)Au/mesoCo_(3)O_(4))for highly efficient and selective CO_(2)*** orderly assembled meso-Co_(3)O_(4)nanorods were prepared via a nanocasting method,offering large surface area and abundant active sites for CO_(2)adsorption and ***,the catalytic activity and selectivity were further improved by molecule-like Ag_(24)Au cluster decoration and reaction temperature *** Ag_(24)Au/meso-Co_(3)O_(4)composite catalyst exhibited an ultrahigh CH_(4)yield rate of 204 mmol·g^(−1)·h^(−1)and a greatly improved CH_(4)selectivity of 82%for CO_(2)hydrogenation,significantly higher than those of pristine meso-Co_(3)O_(4)*** mechanism of the photothermal catalytic performance improvement was verified by CO_(2)temperature-programmed desorption and time-resolved transient photoluminescence,revealing that CO_(2)molecules underwent a vigorous adsorption and rapid activation process over Ag_(24)Au/meso-Co_(3)O_(4).The hot electrons created by the localized surface plasmon resonance effect of Ag_(24)Au clusters facilitated the charge transfer for subsequent multi-electron CO_(2)hydrogeneration processes,resulting in a significant increase in the productivity and selectivity for CO_(2)-to-CH_(4)*** work suggests that the rational coupling of well-defined metal atom clusters and ordered transition metal compound nanostructures could open a new avenue towards photoinduced green chemistry processes for efficient CO_(2)recycling and reutilization.

关键词： mesoporous Co_(3)O_(4) Ag_(24)Au clusters CO_(2)hydrogenation photothermal catalytic

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Focal peliosis hepatis in a colon cancer patient resembling metastatic liver tumor

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World Journal of Gastroenterology 2012年第41期18卷 5999-6002页

作者： Wu-Jun xiong Li-Juan hu Yi-Cheng Jian Yi he Wei Zhou Xin-Lai Guo Ya-Xin zheng Departmentof Gastroenterology Shanghai East Hospital Affiliated to TongjiUniversity Shanghai 200120 China Department of Surgery Shanghai East Hospital Affiliated to Tongji University Shanghai200120 China

Peliosis hepatis(PH) is a rare benign condition characterized by the presence of multiple,randomly distributed,blood filled cystic areas of variable size within the liver *** is difficult to recognize and may be mistaken for neoplasm,metastases or multiple abscesses.A 75-year-old female with a previous history of colon cancer was admitted when a liver mass in the right liver lobe was found 11 mo after surgery during the follow-up *** tomography and magnetic resonance imaging scan of the abdomen were *** initial possible diagnosis was metastatic hepatocellular *** patient underwent excision of the hepatic segment where the nodule was *** pathological diagnosis of the surgical specimen was *** should be considered in the differential diagnosis of new liver lesions in patients whose clinical settings do not clearly favor *** and radiologists must recognize these lesions to minimize the probability of misdiagnosis and inappropriate treatment.

关键词： Differential diagnosis Metastatic liver tumor Peliosis hepatis

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OsWR2 recruits HDA704 to regulate the deacetylation of H4K8ac in the promoter of OsABI5 in response to drought stress

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Journal of Integrative Plant Biology 2023年第7期65卷 1651-1669页

作者： Yalu Guo Yiqing Tan Minghao Qu Kai hong Longjun Zeng Lei Wang Chuxiong Zhuang Qian Qian Jiang hu Guosheng xiong Agricultural Genomics Institute at Shenzhen Chinese Academy of Agricultural SciencesShenzhen 518120China Guangdong Laboratory for Lingnan Modern Agriculture State Key Laboratory for Conservation and Utilization of Subtropical Agro‐bioresourcesCollege of Life SciencesSouth China Agricultural UniversityGuangzhou 510642China Plant Phenomics Research Center Academy of Advanced Interdisciplinary StudiesNanjing Agricultural UniversityNanjing 210095China College of Animal Science and Technology Southwest UniversityChongqing 402460China Yichun Academy of Sciences Yinchun 336000China Center for Agricultural Resources Research Institute of Genetics and Developmental BiologyChinese Academy of SciencesShijiazhuang 050022China State Key Laboratory of Rice Biology China National Rice Research InstituteHangzhou 310000China

Drought stress is a major environmental factor that limits the growth, development, and yield of rice(Oryza sativa L.). Histone deacetylases(HDACs) are involved in the regulation of drought stress responses. HDA704 is an RPD3/HDA1 class HDAC that mediates the deacetylation of H4K8(lysine 8of histone H4) for drought tolerance in rice. In this study, we show that plants overexpressing HDA704(HDA704-OE) are resistant to drought stress and sensitive to abscisic acid(ABA), whereas HDA704 knockout mutant(hda704) plants displayed decreased drought tolerance and ABA *** analysis revealed that HDA704 regulates the expression of ABA-related genes in response to drought stress. Moreover, HDA704 was recruited by a drought-resistant transcription factor,WAX SYNTheSIS REGULATORY 2(Os WR2), and co-regulated the expression of the ABA biosynthesis genes NINE-CIS-EPOXYCAROTENOID DIOXYGENASE 3(NCED3), NCED4, and NCED5 under drought stress. HDA704 also repressed the expression of ABA-INSENSITIVE 5(Os ABI5) and DWARF AND SMALL SEED 1(Os DSS1) by regulating H4K8ac levels in the promoter regions in response to polyethylene glycol 6000 treatment. In agreement, the loss of Os ABI5 function increased resistance to dehydration stress in rice. Our results demonstrate that HDA704 is a positive regulator of the drought stress response and offers avenues for improving drought resistance in rice.

关键词： drought stress HDA704 histone acetylation OsABI5 OsWR2 rice

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Values of macular ganglion cell-inner plexiform layer and 10-2 visual field measurements in detecting and evaluating glaucoma

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 852-860页

作者： Hai-Jian hu Ping Li Bin Tong Yu-Lian Pang hong-Dou Luo Fei-Fei Wang Chan xiong Yu-Lin Yu Hai he Xu Zhang Affiliated Eye Hospital of Nanchang University Jiangxi Research Institute of Ophthalmology and Visual ScienceJiangxi Clinical Research Center for Ophthalmic DiseaseJiangxi Branch of National Clinical Research Center for Ocular DiseasesNanchang 330006Jiangxi ProvinceChina Wuhan Children’s Hospital(Wuhan Maternal and Child healthcare Hospital) Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430015Hubei ProvinceChina

AIM:To assess the performance of macular ganglion cell-inner plexiform layer thickness(mGCIPLT)and 10-2 visual field(VF)parameters in detecting early glaucoma and evaluating the severity of advanced ***:Totally 127 eyes from 89 participants(36 eyes of 19 healthy participants,45 eyes of 31 early glaucoma patients and 46 eyes of 39 advanced glaucoma patients)were *** relationships between the optical coherence tomography(OCT)-derived parameters and VF sensitivity were *** with early glaucoma were divided into eyes with or without central 10°of the VF damages(CVFDs),and the diagnostic performances of OCT-derived parameters were ***:In early glaucoma,the mGCIPLT was significantly correlated with 10-2 VF pattern standard deviation(PSD;with average mGCIPLT:β=-0.046,95%CI,-0.067 to-0.024,Phe mGCIPLT was related to the 24-2 VF mean deviation(MD;with average mGCIPLT:β=0.397,95%CI,0.199 to 0.595,Phe minimum and superotemporal mGCIPLT,the decrease of mGCIPLT in early glaucomatous eyes with CVFDs was more severe than that of early glaucomatous eyes without *** area under the curve(AUC)of the average mGCIPLT(AUC=0.949,95%CI,0.868 to 0.982)was greater than that of the average circumpapillary retinal nerve fiber layer thickness(cpRNFLT;AUC=0.827,95%CI,0.674 to 0.918)and rim area(AUC=0.799,95%CI,0.610 to 0.907)in early glaucomatous eyes with CVFDs versus normal ***:The 10-2 VF and mGCIPLT parameters are complementary to 24-2 VF,cpRNFLT and ONH parameters,especially in detecting early glaucoma with CVFDs and evaluating the severity of advanced glaucoma in group level.

关键词： 10-2 visual field ganglion cell-inner plexiform layer retinal nerve fiber layer thickness glaucoma

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Overexpression of MiR-633 Suppresses the Tumorigenicity of Gastric Cancer Cells and Induces Apoptosis by Targeting MAPK1

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Current Medical Science 2022年第5期42卷 1033-1045页

作者： Hai-long LI Yao-hui SONG zheng-ping DU Yong-hua hu Zhuan-xiong WANG Xi CheN Xing-mei LU Ying-xia CheN Yong-qiang DUAN Xiang-dong Zhu Department of Geriatrics Affiliated Hospital of Gansu University of Traditional Chinese MedicineLanzhou730000China Department of Internal Medicine The First Clinical Medical CollegeGansu University of Chinese MedicineLanzhou730000China Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and The Prevention and Treatment with Traditional Chinese Medicine in Gansu Colleges and Universities Gansu University of Chinese MedicineLanzhou730000China School of Basic Medicine Gansu Vocational College of HealthLanzhou730300China College of Traditional Chinese Medicine Ningxia Medical UniversityYinchuan750004China

Objective MicroRNA(miRNA/miR)-633 is dysregulated in several types of cancers and is involved in ***,the function and role of this miRNA in gastric cancer(GC)are not fully *** aim of the present study was to evaluate miR-633 expression in GC cell lines and in GC tissue *** normal tissue,and to determine its association with clinicopathological *** work was extended to investigate the effects of miR-633 overexpression on tumor cells in *** Reverse transcription-quantitative PCR(RT-qPCR)was used to detect and compare the expression level of miR-633 in GC cells,as well as in GC and normal adjacent tissue *** clinical significance of miR-633 was also ***-633 lentivirus(LV-miR-633)and negative control lentivirus(LV-NC)were generated and used to transduce SGC-7901 and HGC-27 GC cells in order to analyze the effect of miR-633 on their *** effects of miR-633 overexpression on GC cell proliferation,apoptosis,migration and invasion were *** target gene of miR-633 was predicted,then confirmed using a dual luciferase reporter gene assay,RT-qPCR and Western *** MiR-633 was significantly downregulated in GC cell lines,as well as in GC tissue compared with adjacent normal ***,miR-633 expression was associated with the tumor/node/metastasis(TNM)stage,invasion depth,Borrmann classification and lymph node metastasis(Phe LV-NC group,transduction with LV-miR-633 reduced the proliferation,the number of clones,the wound healing rate,the number of invading cells and the number of cells in the G1 phase of the cell cycle(Phe apoptosis rate(Phe expression level of mitogen-activated protein kinase(MAPK)1,high-mobility group box 3(HMGB3),claudin 1(CLDN1)and MAPK13 were downregulated in LV-miR-633-transduced cells(Phe dual luciferase reporter assay confirmed that the 3′-untranslated region of MAPK1 was the t

关键词： miR-633 gastric cancer apoptosis metastasis mitogen-activated protein kinase 1

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Lindqvist-type Polyoxometalates Act as Anti-breast Cancer Drugs via Mitophagy-induced Apoptosis

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Current Medical Science 2024年第4期44卷 809-819页

作者： Chen-guang YAO Zi-jia ZHAO Ting TAN Jiang-ning YAN Zhong-wei CheN Jun-tao xiong Han-luo LI Yan-hong WEI Kang-hong hu Sino-German Biomedical Center Hubei Provincial Key Laboratory of Industrial MicrobiologyCooperative Innovation Center of Industrial Fermentation(Ministry of Education&Hubei Province)Key Laboratory of Fermentation Engineering(Ministry of Education)National“111”Center for Cellular Regulation and Molecular PharmaceuticsHubei University of TechnologyWuhan430068China Center for Evaluation of hubei Medical Products Administration Wuhan430068China

Objective Lindqvist-type polyoxometalates(POMs)exhibit potential antitumor *** study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying *** Using different cancer cell lines,the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side *** colony formation assay,autophagy detection,mitochondrial observation,qRT-PCR,Western blotting,and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related *** MO-4,a Lindqvist-type POM linking a proline at its side strain,was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer *** was found that MO-4 induced the apoptosis of multiple types of breast cancer ***,MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species(ROS)levels and resulting in *** vivo,breast tumor growth and distant metastasis were significantly reduced following MO-4 *** Collectively,the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.

关键词： antitumor breast cancer polyoxometalate mitochondria mitophagy

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Preliminary delivery efficiency prediction of nanotherapeutics into crucial cell populations in bone marrow niche

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Asian Journal of Pharmaceutical Sciences 2023年第6期18卷 113-125页

作者： huijuan Chen Anzhi hu Mengdi Xiao Shiyi hong Jing Liang Quanlong Zhang Yang xiong Mancang Gu Chaofeng Mu School of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Center for Synthetic Biochemistry Shenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Several crucial stromal cell populations regulate hematopoiesis and malignant diseases in bone marrow *** regulation of these cell types can remodel niches and develop new *** nanocarriers have been developed to transport drugs into the bone marrow ***,the delivery efficiency of these nanotherapeutics into crucial niche cells is still unknown,and there is no method available for predicting delivery efficiency in these cell ***,we constructed a three-dimensional bone marrow niche composed of three crucial cell populations:endothelial cells(ECs),mesenchymal stromal cells(MSCs),and osteoblasts(OBs).Mimetic niches were used to detect the cellular uptake of three typical drug nanocarriers into ECs/MSCs/OBs in *** than 5%of nanocarriers were taken up by three stromal cell types,and most of themwere located in the extracellular *** efficiency in sinusoidal ECs,arteriole ECs,MSCs,and OBs in vivo was *** correlation analysis showed that the cellular uptake of three nanocarriers in crucial cell types in vitro is positively linear correlated with its delivery efficiency in *** delivery efficiency into MSCs was remarkably higher than that into ECs and OBs,no matterwhat kind of *** overall efficiency into sinusoidal ECswas greatly lower than that into arteriole *** nanocarriers were hard to be delivered into OBs(heir cellular uptake in bone marrow niches in *** study provided the methodology for niche-directed nanotherapeutics development.

关键词： Bone marrow niche mimicking Drug delivery prediction Nanotherapeutics Bone marrow stromal cells

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