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Camouflaging attenuated Salmonella by cryo-shocked macrophages for tumor-targeted therapy

Signal Transduction and Targeted Therapy 2024年第2期9卷 709-723页

作者： Leyang Wu Zengzheng Du Lin Li Liyuan Qiao Shuhui Zhang Xingpeng Yin Xiaoyao Chang Chenyang Li Zichun Hua The State Key Laboratory of Pharmaceutical Biotechnology and Department of Neurology of Nanjing Drum Tower Hospital School of Life Sciences and The Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing 21008 JiangsuChina Nanjing Generecom Biotechnology Co. LtdNanjing 210023China changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma laboratories Inc Changzhou 213164 JiangsuChina School of Biopharmacy China Pharmaceutical UniversityNanjing 210023 JiangsuChina

Live bacteria-mediated antitumor therapies mark a pivotal point in cancer ***,the difficulty in reconciling the safety and efficacy of bacterial therapies has limited their *** bacterial tumor-targeted delivery while maintaining biosafety is a critical hurdle for the clinical translation of live microbial therapy for ***,we developed“dead”yet“functional”Salmonella-loaded macrophages using liquid nitrogen cold shock of an attenuated Salmonella typhimurium VNP20009-contained macrophage cell *** obtained“dead”macrophages achieve an average loading of approximately 257 live bacteria per 100 *** engineered cells maintain an intact cellular structure but lose their original pathogenicity,while intracellular bacteria retain their original biological activity and are delay freed,followed by ***“Trojan horse”-like bacterial camouflage strategy avoids bacterial immunogenicity-induced neutrophil recruitment and activation in peripheral blood,reduces the clearance of bacteria by neutrophils and enhances bacterial tumor enrichment efficiently after systemic ***,this strategy also strongly activated the tumor microenvironment,including increasing antitumor effector cells(including M1-like macrophages and CD8+Teffs)and decreasing protumor effector cells(including M2-like macrophages and CD4+Tregs),and ultimately improved antitumor efficacy in a subcutaneous H22 tumor-bearing mouse *** cryo-shocked macrophage-mediated bacterial delivery strategy holds promise for expanding the therapeutic applications of living bacteria for cancer.

关键词： shock holds maintain

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Status of IPC-4101F

Status of IPC-4101F

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第十八届中国覆铜板技术·市场研讨会

作者： Douglas J.Sober microtek changzhou laboratories

The publication of IPC-4101E released in March 2017 has introduced a tightened definition of contamination that is allowed for copper-clad laminates and prepregs. Otherwise the changes in this revision are minimal. For IPC-4101 Revision F, there are a number of changes that will affect CCL makers world-wide including new specification sheets, introduction of FR-15.0 and FR-15.1, and the new IPC Validation Services certification program. As a primary contributor to IPC-4101 and the Base Materials General Chairman for IPC, Mr. Sober will provide details of these standards and how they will affect the electronics supply chain.

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Microwave-assisted Hydrothermal Synthesis of Carbon Materials with Tunable Microstructure

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Journal of Wuhan University of Technology(Materials Science) 2017年第5期32卷 1032-1037页

作者：夏群 JIA Jiajia 赵善宇 ZHU Pinghua 徐海珣 Department of Civil Engineering Changzhou University Changzhou 213164 China Swiss Federal laboratories for Materials Science and Technology CH-8600 Diibendorf Switzerland

A facile microwave-assisted hydrothermal route has been developed for a synthesis of versatile carbon materials. The monosaccharide fructose aqueous solution was adopted as the starting material, and the p H of the solution was adjusted to be in acidic（pH 4）, neutral（pH 7） and basic（pH 10.5） conditions. The p H buffered fructose solutions were treated at different temperatures by a microwave-assisted hydrothermal technique. As-prepared carbon materials displayed p H and temperature dependent multi-morphologies（porous, spherical or core-shell）, which were determined by transmission and scanning electron microscopic analyses（TEM and SEM）. And the hypothesis of dehydration mechanism of hydrothermal synthesis was analyzed by ultraviolet extinction and Fourier transform infrared spectroscopy. It was found that as compared with normal hydrothermal synthesis, microwave assistance could efficiently increase the production yield and improve the spherical geometry of the carbon particles in neutral condition. By changing the p H of the system, acidic p H induces aggregation of the spheres, while basic p H produces more trends toward core-shell or sponge-like porous structure. The study opens a novel route to the production of polytropic carbon materials and suggests a potential niche market established from the green synthesis.

关键词： carbon material hydrothermal microwave tunable structure

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A Convenient Fluorescent-labeled Assay for in vitro Measurement of DNA Mismatch Repair Activity

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Biomedical and Environmental Sciences 2010年第6期23卷 496-501页

作者： SHI-YING LI XIANG-YU ZHANG XIN ZHANG YAN LAN ZI-CHUN HUA The State Key Laboratory of Pharmaceutical Biotechnology and Jiangsu Center of Hepatobiliary Diseases School of Stomatology and Affiliated Stomatological Hospital Nailing University Nanjing 210093 Jiangsu China changzhou High-Tech Research Institute of Nanjing University and changzhou Target Pharma laboratories Inc. Changzhou 213164 Jiangsu China

Objective The assay of DNA mismatch repair （MMR） activity can be used as a biomarker for environmental condition detection and human disease diagnosis. Radioactive 32p-endlabeled DNA containing mismatch is extensively used as the substrate for MMR activity analyses. The aim of the present study is to develop a simple non-radioactive, but equally specific and sensitive method for the MMR activity assay. Methods A fluorescent label was chosen to replace the radioactive isotope label. Sensitive evaluation of the fluorescent label was carried out for the first time, and then the fluorescent label was compared with the isotope label in the MMR activity and DNA binding assays. Result LOD （limit of detection） of the fluorescent label was about 0.1 fmol and the relative signal strength displayed a pretty good linear relationship. Moreover, the fluorescent label method has equivalent sensitivity and performance as compared with the classical radioactive method in experiments. Conclusion In light of the sensitivity, reproducibility, safety, rapidity and long lifespan of the fluorescent label, this improved method can be applied to evaluation of biologic and toxic effects of environmental pollutants on man and other forms of life.

关键词： Fluorescent label MMR activity EMSA TDG

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Extracellular signal regulated kinase 5 promotes cell migration,invasion and lung metastasis in a FAK-dependent manner

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Protein & Cell 2020年第11期11卷 825-845页

作者： Weiwei Jiang Fangfang Cai Huangru Xu Yanyan Lu Jia Chen Jia Liu Nini Cao Xiangyu Zhang Xiao Chen Qitai Huang Hongqin Zhuang Zi-Chun Hua The State Key Laboratory of Pharmaceutical Biotechnology College of Life SciencesNanjing UniversityNanjing 210023China changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma laboratories Inc. Changzhou 213164China

This study was designed to evaluate ERK5 expression in lung cancer and malignant melanoma progression and to ascertain the involvement of ERK5 signaling in lung cancer and *** show that ERK5 expression is abundant in human lung cancer samples,and elevated ERK5 expression in lung cancer was linked to the acquisition of increased metastatic and invasive ***,we observed a significant correlation between ERK5 activity and FAK expression and its phosphorylation at the Ser910 ***,ERK5 increased the expression of the transcription factor USF1,which could transcriptionally upregulate FAK expression,resulting in FAK signaling activation to promote cell *** also provided evidence that the phosphorylation of FAK at Ser910 was due to ERK5 but not ERK1/2,and we then suggested a role for Ser910 in the control of cell *** addition,ERK5 had targets in addition to FAK that regulate epithelial-to-mesenchymal transition and cell motility in cancer *** together,our findings uncover a cancer metastasis-promoting role for ERK5 and provide the rationale for targeting ERK5 as a potential therapeutic approach.

关键词： ERK5 lung cancer melanoma metastasis FAK USF1 EMT

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Bacteria-mediated tumor-targeted delivery of tumstatin(54-132)significantly suppresses tumor growth in mouse model by inhibiting angiogenesis and promoting apoptosis

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Frontiers of Medicine 2022年第6期16卷 873-882页

作者： Feifei Bao Mengjie Liu Wenhua Gai Yuwei Hua Jing Li Chao Han Ziyu Zai Jiahuang Li Zichun Hua The State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing210023China changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma laboratories Inc. Changzhou213164China

Tumor growth is an angiogenesis-dependent process and accompanied by the formation of hypoxic *** is a tumor-specific angiogenesis inhibitor that suppresses the proliferation and induces the apoptosis of tumorous vascular endothelial ***20009,an attenuated Salmonella typhimurium strain,preferentially accumulates in the hypoxic areas of solid *** this study,a novel Salmonella-mediated targeted expression system of tumstatin(VNP-Tum5)was developed under the control of the hypoxia-induced J23100 promoter to obtain anti-tumor efficacy in *** with VNP-Tum5 effectively suppressed tumor growth and prolonged survival in the mouse model of B16F10 ***-Tum5 exhibited a higher efficacy in inhibiting the proliferation and inducing the necrosis and apoptosis of B16F10 cells in vitro and in vivo compared with VNP(control).VNP-Tum5 significantly inhibited the proliferation and migration of mouse umbilical vascular endothelial cells to impede ***-Tum5 downregulated the expression of anti-vascular endothelial growth factor A,platelet endothelial cell adhesion molecule-1,phosphorylated phosphoinositide 3 kinase,and phosphorylated protein kinase B and upregulated the expression of cleaved-caspase 3 in tumor *** study is the first to use tumstatin-transformed VNP20009 as a tumor-targeted system for treatment of melanoma by combining anti-tumor and anti-angiogenic effects.

关键词： Salmonella VNP20009 tumstatin B16F10 melanoma apoptosis angiogenesis

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Tannic acid assisted anti-TNF-αnanobody assembly modulating the epithelial barrier dysregulation of allergic rhinitis

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Nano Research 2023年第7期16卷 9781-9791页

作者： Shuilian Fu Zhiting Cao Baolian Huang Te Yin Chujun Huang Zhiqian Bi Yingying Yao Xiaoyao Chang Hongqin Zhuang Zi-Chun Hua The State Key Laboratory of Pharmaceutical Biotechnology College of Life SciencesNanjing UniversityNanjing 210023China changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma laboratories Inc. Changzhou 213164China School of Biopharmacy China Pharmaceutical UniversityNanjing 211198China

The derailed nasal epithelial barrier is associated with the disorder of tight junctions(TJ)function or expression,leading to more penetration of allergens to the barrier,accompanied by the release of cytokines,which develop allergic rhinitis(AR).Considering the increasing AR disease incidence worldwide,there is still an urgent unmet medical need to develop new *** necrosis factor-alpha(TNF-α)inhibitors have been applied in treating autoimmune ***,their roles in AR remain *** this study,anti-TNF-αnanobody(V)was assembled with tannic acid(V/TA)as a functional antibody drug candidate which could inhibit the release of the cytokines in ovalbumin(OVA)-induced AR murine *** receiving V/TA treatment,the infiltration level of inflammatory cells,and the number of mucus-secreting cells and mast cells in the nasal mucosa recovered to a relatively normal *** mechanism of action research revealed that the efficacy of V/TA was accompanied by the restricted level of TJ molecules:zonula occluden-1(ZO-1),occludin,claudin-1,and *** therapeutic effect of the anti-TNF-αnanobody against AR was enhanced with the tannic acid assisted without any toxicity *** study supplied a promising delivery strategy of TNF-αinhibitor for the effective treatment of complicated allergic rhinitis disease,with an advantage in restoring effect on the AR-caused epithelial barrier defects than the commercial drug Infliximab.

关键词： allergic rhinitis tumor necrosis factor-alpha(TNF-α)nanobody nanoparticles epithelial permeability tight junctions

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Phosphatidylserine externalized on the colonic capillaries as a novel pharmacological target for IBD therapy

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Signal Transduction and Targeted Therapy 2021年第7期6卷 2186-2195页

作者： Xuerui Zhang Lulu Song Lin Li Banghui Zhu Lina Huo Zhaoqing Hu Xinran Wang Jie Wang Mengyue Gao Jing Zhang Zichun Hua The State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjingChina changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma laboratories Inc ChangzhouChina School of Biopharmacy China Pharmaceutical UniversityNanjingChina

Inflammatory bowel disease(IBD)is a chronic and relapsing disorder for many people associated with poor *** there are some clinical drugs for IBD treatment,the development of effective therapeutics on IBD patients has always been ***,we show that externalized phosphatidylserine(PS)is observed on the surface of colonic *** A5(ANXA5)with high affinity for PS has a good targeting to the colon and effectively alleviates experimental *** contrast,ANXA5 mutant(A5m)lacking the PS-binding ability,has no accumulation in the colon and no therapeutic effects on *** investigations indicate that ANXA5 reduces the inflammatory cell infiltration by inhibiting endothelial cell activation dependent on PS-binding *** the increasing of PS exposure on activated HUVECs(human umbilical vein endothelial cells),ANXA5 binding induces the internalization of TLR4 via PS-dependent *** provide new insights on the molecular mechanism of ANXA5 for its anti-inflammatory *** data suggest that PS-externalization is a potential target of ANXA5 aiming at targeted drug delivery(TDD)for IBD treatment.

关键词： colonic colon drugs

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Structural Characteristics and Photocatalytic Activity of Ambient Pressure Dried SiO2/TiO2 Aerogel Composites by One-step Solvent Exchange/Surface Modification

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Journal of Wuhan University of Technology(Materials Science) 2016年第1期31卷 80-86页

作者：徐海珣朱平华 WANG Lijiu JIANG Zuqiang 赵善宇 Department of Environmental Engineering Changzhou UniversityChangzhou213164China Institute of Building Materials Dalian University of TechnologyDalian116024China CNBM International Engineering Co. L TDBeijing 100048China Swiss Federal laboratories for Materials Science and Technology CH-8600 DiibendorfSwitzerland

An ambient pressure synthesis of SiO2/TiO2 binary aerogel was prepared through the low-cost precursors of titanium tetrachloride（TiCl4） and sodium silicate（Na2O·nSiO2）.After gelation,solvent exchange and surface modification were performed simultaneously and the modified gel was finally dried under ambient *** analyses by transmission electron microscope（TEM） indicate that fabricated SiO2/TiO2 aerogel composite shows similar sponge-like nanostructure as silica aerogel,and the Brunauer-EmmettTeller（BET） analysis shows that the specific surface area of the composite reaches 605 m^2/g,and the average pore size is 9.7 *** binary aerogel exhibits significant photocatalytic performance in this paper for treating model pollutant of methyl orange（MO）,and the decolorizing efficiency of MO is detected as 84.9%after 210 mins exposure to UV light *** gel suspends in the water so as to separate from solution for reuse,and after 4 times recycling,70%degradation efficiency can be easily reached when composite catalyzed system is exposed for 210 mins under UV irradiation.

关键词： photocatalytic activity water glass SiO2/TiO2 binary aerogel ambient drying

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ADT-OH improves intestinal barrier function and remodels the gut microbiota in DSS-induced colitis

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Frontiers of Medicine 2023年第5期17卷 972-992页

作者： Zhiqian Bi Jia Chen Xiaoyao Chang Dangran Li Yingying Yao Fangfang Cai Huangru Xu Jian Cheng Zichun Hua Hongqin Zhuang The State Key Laboratory of Pharmaceutical Biotechnology College of Life SciencesNanjing UniversityNanjing210023China changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma laboratories Inc. Changzhou213164China School of Biopharmacy China Pharmaceutical UniversityNanjing211198China Institute of Neuroscience Soochow UniversitySuzhou215123China

Owing to the increasing incidence and prevalence of inflammatory bowel disease(IBD)worldwide,effective and safe treatments for IBD are urgently *** sulfide(H2S)is an endogenous gasotransmitter and plays an important role in *** date,H2S-releasing agents are viewed as potential anti-inflammatory *** slow-releasing H_(2)S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione(ADT-OH),known as a potent therapeutic with chemopreventive and cytoprotective properties,has received attention ***,we reported its anti-inflammatory effects on dextran sodium sulfate(DSS)-induced acute(7 days)and chronic(30 days)*** found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon ***,ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B *** vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression *** addition,ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter,Mucispirillum,Parasutterella,and *** ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory ***,ADT-OH is safe without any short-term(5 days)or long-term(30 days)toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.

关键词： inflammatory bowel disease ADT-OH intestinal permeability gut microbiota

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