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Tandem Molecular Self-Assembly Selectively Inhibits Lung cancer cells by Inducing Endoplasmic Reticulum Stress

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Research 2019年第1期2019卷 31-41页

作者： Debin Zheng Yumiao chen Sifan Ai Renshu Zhang Zhengfeng Gao chunhui Liang Li cao Yaoxia chen Zhangyong Hong Yang Shi Ling Wang Xingyi Li Zhimou Yang Key Laboratory of bioactive Materials Ministry of EducationCollege of Life SciencesKey Laboratory of Medicinal Chemical BiologyCollaborative Innovation Center of Chemical Science and Engineeringand National Institute of Functional MaterialsNankai UniversityTianjin 300071China School of Ophthalmology&Optometry and Eye Hospital Wenzhou Medical Universityand Wenzhou Institute of Biomaterials and EngineeringCNITECHCASWenzhou 325035China college of pharmacy Nankai UniversityTianjin 300071China Jiangsu center for the collaboration and Innovation of cancer biotherapy Cancer InstituteXuzhou Medical UniversityXuzhouJiangsuChina

The selective formation of nanomaterials in cancer cells and tumors holds great promise for cancer diagnostics and *** now,most strategies rely on a single trigger to control the formation of nanomaterials in *** combination of two or more triggers may provide for more sophisticated means of *** this study,we rationally designed a molecule(comp.1)capable of responding to two enzymes,alkaline phosphatase(ALP),and *** the A549 lung cancer cell line showed elevated levels of extracellular ALP and intracellular reductase,we demonstrated that comp.1 responded in a stepwise fashion to those two enzymes and displayed a tandem molecular self-assembly *** selective formation of nanofibers in the mitochondria of the lung cancer cells led to the disruption of the mitochondrial membrane,resulting in an increased level of reactive oxygen species(ROS)and the release of cytochrome c(cyt c).ROS can react with proteins,resulting in endoplasmic reticulum(ER)stress and the unfolded protein response(UPR).This severe ER stress led to disruption of the ER,formation of vacuoles,and ultimately,apoptosis of the A549 ***,comp.1 could selectively inhibit lung cancer cells in vitro and A549 xenograft tumors in *** study provides a novel strategy for the selective formation of nanomaterials in lung cancer cells,which is powerful and promising for the diagnosis and treatment of lung cancer.

关键词： Lung holds stepwise

Silica Nanoparticles with Virus-Mimetic Spikes Enable Efficient siRNA Delivery In Vitro and In Vivo

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Research 2023年第3期2022卷 281-294页

作者： Jianye Fu Wenwei Han Xue Zhang Yutong Sun Rajendra bhadane bo Wei Li Li Liangmin Yu Jinbo Yang Jessica MRosenholm Outi MHSalo-Ahen Taojian Fan bin Zhang Wageh Swelm Ahmed AAl-Ghamdi Lin Xia Han Zhang Meng Qiu Hongbo Zhang Xin Wang Key Laboratory of Marine drugs Chinese Ministry of EducationSchool of Medicine and PharmacyOcean University of ChinaQingdao 266003China collaborative Innovation center for Optoelectronic Science&Technology International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of EducationInstitute of Microscale OptoelectronicsCollege of Physics and Optoelectronic EngineeringShenzhen UniversityShenzhen 518060China Key Laboratory of Marine chemistry Theory and Technology(Ocean University of china) Ministry of EducationQingdao 266100China college of chemistry and chemical Engineering China University of PetroleumQingdao 266555China. Pharmaceutical sciences Laboratory Åbo Akademi University20520 TurkuFinland Structural bioinformatics Laboratory BiochemistryÅbo Akademi University20520 TurkuFinland. center for Innovation Marine drug Screening&Evaluation Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266237China Marine biomedical Research Institute of Qingdao Qingdao 266100China Department of Physics Faculty of ScienceKing Abdulaziz UniversityJeddah 21589Saudi Arabia Hangzhou No.14 High School Hangzhou 310000China Turku bioscience centre University of Turku andÅbo Akademi University20520 TurkuFinland

Oligonucleotide-based therapy has experienced remarkable development in the past 2 decades,but its broad applications are severely hampered by delivery *** used viral vectors and lipid nanovectors are suffering from immune clearance after repeating usage or requiring refrigerated transportation and storage,*** this work,amino-modified virus-mimetic spike silica nanoparticles(NH_(2)-SSNs)were fabricated using a 1-pot surfactant-free approach with controlled spike lengths,which were demonstrated with excellent delivery performance and biosafety in nearly all cell types and *** indicated that NH2-SSNs entered cells by spike-dependent cell membrane docking and dynamin-dependent *** positively charged spikes with proper length on the surface can facilitate the efficient encapsulation of RNAs,protect the loaded RNAs from degradation,and trigger an early endosome escape during intracellular trafficking,similarly to the cellular internalization mechanism of *** the fantastic properties of NH_(2)-SSNs in nucleic acid delivery,it revealed that nanoparticles with solid spikes on the surface would be excellent vehicles for gene therapy,presenting self-evident advantages in storage,transportation,modification,and quality control in large-scale production compared to lipid nanovectors.

关键词： surfactant loaded transportation

Anti-inflammatory and Anti-oxidative Effects of the Ethanol Extract of cryptocarya densiflora blume in Lipopolysaccharide-Stimulated RAW264,7 Mouse Macrophages

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Journal of pharmacy and Pharmacology 2014年第1期2卷 26-37页

作者： Ji-Won Park Ok-Kyoung Kwon Doo-Young Kim Jung-Hee Kim In Sik Shin Sei-Ryang Oh Sang-Woo Lee Jae-Hong Kim Hang Jin Wan Yi Lee Kyung-Seop Ahn Natural Medicine Research center Korea Research Institute of Bioscience and Biotechnology 30 Yeongudanji-ro Ochang-eupCheongwon-gun Chungbuk 363-883 Republic of Korea college of Life sciences and biotechnology University of Korea Anam-dong 5-ga Seongbuk-gu Seoul 136-701 Republic ofKorea Department of Toxicology College of Pharmacy University of Chungnam National Yuseong-gu Daejeon 305-764 Republic ofKorea International biological Material Research center Research Institute of Bioscience and Biotechnology Yuseong-gu Daejeon305-806 Republic of Korea Yunnan Academy of Agricultural sciences Medicinal Plants Research Institute Beijing 2238 China

cD （cryptocarya densiflora） blume has traditionally been used as an herbal medicine. In this study, the effects of cDEE （cD ethanol extract） on inflammation were investigated in LPS （lipopolysaccharide）-stimulated mouse RAW264.7 macrophages. We investigated the effects of cDEE on the production of NO, PGE2 interleukin （IL）-6, IL-1β, and tumor necrosis factor （TNF）-α in LPS-stimulated RAW264.7 cells. We measured the mRNA or protein expression of the pro-inflammatory mediators induced by cDEE in LPS-stimulated RAW264.7 cells. We explored the expression of Nrf-2, heme oxygenase （HO）-I and NADPH-quinone oxidoreductase （NQO）-I to elucidate the antioxidative mechanisms. cDEE significantly inhibited the production of NO, PGE2, IL-6, IL-1β and TNF-α in LPS-stimulated RAW264.7 cells. cDEE suppressed the mRNA or protein expression of iNOS, cOX-2, and the MAPKs with a reduction in the translocation of NF-κb in LPS-stimulated RAW264.7 cells. In addition, cDEE significantly increased the expression of HO-I and NQO-1 with an increase in the translocation of Nrf-2 into the nucleus. These results indicate that cDEE inhibits the LPS-induced inflammatory and oxidative responses via suppression of NF-κb activation and the enhancement of Nrf2 activation. We suggest that cDEE may be therapeutic for treating inflammatory diseases.

关键词： cryptocarya densiflora inflammation MAPK NF-κb Nrf-2.

Target specificity of selective bioactive compounds in blocking α-dystroglycan receptor to suppress Lassa virus infection: an in silico approach

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The Journal of biomedical Research 2021年第6期35卷 459-473页

作者： Adittya Arefin Tanzila Ismail Ema Tamnia Islam MdSaddam Hossen Tariqul Islam Salauddin Al Azad MdNasir Uddin badal MdAminul Islam Partha biswas Nafee Ul Alam Enayetul Islam Maliha Anjum Afsana Masud MdShaikh Kamran Ahsab Rahman Parag Kumar Paul Wolfson Institute for biomedical Research Division of MedicineUniversity College LondonLondon WC1E6AEUK Department of biochemistry and Microbiology North South UniversityDhaka 1229Bangladesh Faculty of Life sciences and Medicine Zhejiang Sci-Tech UniversityHangzhouZhejiang 310018China Faculty of pharmacy International Islamic University MalaysiaKuantanPahang 25200Malaysia School of biotechnology Jiangnan UniversityWuxiJiangsu 214122China Department of biomedical Technology Tampere UniversityTampere 33014Finland Department of Genetic Engineering and biotechnology Jashore University of Science and TechnologyJashore 7408Bangladesh Department of Genetic Engineering and biotechnology University of ChittagongChittagong 4331Bangladesh Applied Statistics and Data Science Jahangirnagar UniversityDhaka 1342Bangladesh Department of Mathematics and Natural sciences Brac UniversityDhaka 1212Bangladesh Department of Electrical and Electronic Engineering United International UniversityDhaka 1212Bangladesh.

Lassa hemorrhagic fever,caused by Lassa mammarenavirus(LASV)infection,accumulates up to 5000 deaths every ***,there is no vaccine available to combat this *** this study,a library of 200 bioactive compounds was virtually screened to study their drug-likeness with the capacity to block theα-dystroglycan(α-DG)receptor and prevent LASV *** rigorous absorption,distribution,metabolism,and excretion(ADME)and quantitative structure-activity relationship(QSAR)profiling,molecular docking was conducted with the top ligands against theα-DG *** compounds chrysin,reticuline,and 3-caffeoylshikimic acid emerged as the top three ligands in terms of binding ***-docking analysis revealed that interactions with Arg76,Asn224,Ser259,and Lys302 amino acid residues of the receptor protein were important for the optimum binding affinity of *** dynamics simulation was performed comprehensively to study the stability of the protein-ligand ***-depth assessment of root-mean-square deviation(RMSD),root mean square fluctuation(RMSF),polar surface area(PSA),b-Factor,radius of gyration(Rg),solvent accessible surface area(SASA),and molecular surface area(MolSA)values of the protein-ligand complexes affirmed that the candidates with the best binding affinity formed the most stable protein-ligand *** authenticate the potentialities of the ligands as target-specific drugs,an in vivo study is underway in real time as the continuation of the research.

关键词： LASV infection α-dystroglycan receptor bioactive compounds target specificity molecular docking molecular dynamic simulations

Single-cell analyses reveal cannabidiol rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with anti-PD-1 in colon cancer

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药物分析学报:英文版 2023年第7期13卷 726-744页

作者： Xiaofan Sun Lisha Zhou Yi Wang Guoliang Deng Xinran cao bowen Ke Xiaoqi Wu Yanhong Gu Haibo cheng Qiang Xu Qianming Du Hongqi chen Yang Sun Department of Rheumatology and Immunology Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing210008China State Key Laboratory of Pharmaceutical biotechnology School of Life SciencesNanjing UniversityNanjing210023China colon and Rectal Surgery Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineNanjing210001China Laboratory of Anesthesia and critical care Medicine Department of AnesthesiologyTranslational Neuroscience CenterWest China Hospital and State Key Laboratory of BiotherapySichuan UniversityChengdu610044China Genergy bio-technology(Shanghai)co. LtdShanghai200241China The First Affiliated Hospital of Nanjing Medical University Jiangsu Province HospitalNanjing210029China Jiangsu collaborative Innovation center of Traditional chinese Medicine in Prevention and Treatment of Tumor The First Clinical College of Nanjing University of Chinese MedicineNanjing210023China General clinical Research center Nanjing First HospitalNanjing Medical UniversityNanjing210006China School of basic Medicine&clinical pharmacy China Pharmaceutical UniversityNanjing210009China Department of General Surgery Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai200030China Jiangsu Key Laboratory of New drug Research and clinical pharmacy Xuzhou Medical UniversityXuzhouJiangsu221004China

colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to ***(cbD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic *** study aimed to elucidate the specific anticancer mechanism of cbD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAc sequencing(scATAc-seq)***,we report that cbD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAc sequencing results showed that cbD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and ***,cbD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor ***,cbD altered the metabolic pattern of macrophages and related anti-tumor signaling *** found that cbD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase b signaling pathway and related downstream target ***,cbD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted *** together,we provide new insights into the anti-tumor effects of cbD.

关键词： scRNA-seq scATAc-seq cannabidiol colorectal cancer Tumor microenvironment Macrophage

Multinational survey on the preferred approach to management of barrett’s esophagus in the Asia-Pacific region

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World Journal of Gastrointestinal Oncology 2021年第4期13卷 279-294页

作者： Guan Sen Kew Alex Yu Sen Soh Yeong Yeh Lee Takuji Gotoda Yan-Qing Li Yan Zhang Yiong Huak chan Kewin Tien Ho Siah Daniel Tong Simon Ying Kit Law Andrew Ruszkiewicz Ping-Huei Tseng Yi-chia Lee chi-Yang chang Duc Trong Quach chika Kusano Shobna bhatia Justin che-Yuen Wu Rajvinder Singh Prateek Sharma Khek-Yu Ho Department of Gastroenterology and Hepatology University Medicine ClusterNational University Health SystemSingapore 119228Singapore Department of Gastroenterology and Hepatology National University HospitalNational University Health SystemSingapore 119074Singapore School of Medical sciences Universiti Sains MalaysiaPenang 11800Malaysia Division of Gastroenterology and Hepatology Department of MedicineNihon University School of MedicineTokyo 173-8610Japan Department of Gastroenterology Laboratory of Translational GastroenterologyQilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Yong Loo Lin School of Medicine National University of SingaporeSingapore 119228Singapore Department of Surgery The University of Hong KongHong Kong PokfulamHong KongChina Department of Pathology SA PathologyAdelaide 5112Australia Department of Internal Medicine National Taiwan University HospitalTaipei 100Taiwan Department of Internal Medicine Fu Jen Catholic University HospitalTaipei 24352Taiwan Department of Internal Medicine University of Medicine and Pharmacy at Hochiminh CityVietnamHochiminh 70000Viet Nam Department of Gastroenterology Seth GS Medical College and King Edward Memorial HospitalMumbai 400012India Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina Department of Gastroenterology Lyell McEwin HospitalUniversity of AdelaideAdelaide 64128Australia Department of Gastroenterology and Hepatology Kansas City VA Medical CenterKansas CityKS 64128United States Department of Medicine National University HospitalSingapore 119074Singapore

bAcKGROUND Major societies provide differing guidance on management of barrett’s esophagus(bE),making standardization *** To evaluate the preferred diagnosis and management practices of bE among Asian *** Endoscopists from across Asia were invited to participate in an online questionnaire comprising eleven questions regarding diagnosis,surveillance and management of *** Five hundred sixty-nine of 1016(56.0%)respondents completed the survey,with most respondents from Japan(n=310,54.5%)and china(n=129,22.7%).Overall,the preferred endoscopic landmark of the esophagogastric junction was squamocolumnar junction(42.0%).Distal palisade vessels was preferred in Japan(59.0%vs 10.0%,Pcolumnar junction was preferred(59.5%vs 27.4%,Pc and M criteria all the *** was never used by 46.1%of Japanese,whereas 84.2%outside Japan,endoscopists used it to varying extents(Pcopists(70.8%)would survey long-segment bE without dysplasia every two *** to Seattle protocol was poor with only 6.3%always performing it.73.2%of Japanese never did it,compared to 19.3%outside Japan(Pc bE was proton pump inhibitor only when the patient was symptomatic or had *** bE with low-grade dysplasia,6-monthly surveillance was preferred in 61.9%within Japan vs 47.9%outside Japan(PcONcLUSION Diagnosis and management of bE varied within Asia,with stark contrast between Japan and outside *** Asian endoscopists chose squamo-columnar junction to be the landmark for esophagogastric junction,which is *** also did not consistently use Prague criteria,and Seattle *** of standardization,education and research are possible reasons.

关键词： barrett's esophagus Survey Asia-Pacific Asian barrett's consortium Prague criteria Seattle protocol

Kadsura coccinea:A rich source of structurally diverse and biologically important compounds

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chinese Herbal Medicines 2020年第3期12卷 214-223页

作者： Yu-pei Yang Nusrat Hussain Liu Zhang Yan-zhe Jia Yu-qing Jian bin Li Muhammad Iqbal choudhary Atta-ur Rahman Wei Wang TcM and Ethnomedicine Innovation(&)Development International Laboratory School of PharmacyHunan University of Chinese MedicineChangsha 410208China H.E.J.Research Institute of chemistry International Center for Chemical and Biological SciencesUniversity of KarachiKarachi 75270Pakistan

Kadsura coccinea belongs to medicinally important genus Kadsura from the Schisandraceae *** has been used in traditional chinese medicine(TcM)for the treatment of rheumatoid arthritis and gastroenteric *** initial phytochemical work focused on the identification of some structurally novel and diverse natural products,which turned the attention of many researchers towards this *** far,202 compounds have been reported in this *** and terpenoids were found as the main chemical constituents of this *** of the triterpenoids and sesquiterpenoids with novel structures are of particular interest for natural product *** isolated compounds of this plant have shown different bioactivities including anti-tumor,anti-HIV,anti-inflammatory,nitric oxide(NO)production inhibitory and other pharmacological *** review systematically summarizes all the phytochemical and pharmacological work done so far on ***,and can be used as a reference for future research on this plant.

关键词： Kadsura coccinea(Lem.)A.c.Smith Heilaohu lignans pharmacology rheumatoid arthritis triterpenoids

Flavonoid c-glycosides from the seeds of Hovenia dulcis Thunb.

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Journal of chinese Pharmaceutical sciences 2020年第11期29卷 813-818页

作者： Fangfang Xu biao Sun Xiaoqi Zhang bo Liu Guangzhou Key Laboratory of chirality Research on Active components of Traditional chinese Medicine the Second Clinical Medicial CollegeGuangzhou University of Chinese MedicineGuangzhou 510006China Guangdong Provincial Engineering Research center for Modernization of TcM College of PharmacyJinan UniversityGuangzhou 510632China

Ten known flavonoid c-glycosides identified as 2′′-O-β-D-glucopyranosyl isovitexin(1),spinosin(2),6′′′-acetyl spinosin(3),6′′′-p-hydroxycinnamoyl-2′′O-β-D-glucopyranosyl isovitexin(4),6′′′-p-hydroxy-cinnamoyl spinosin(5),6′′′-(E)-feruloyl O-β-Dglucopyranosyl isovitexin(6),isospinosin(7),isovitexin(8),swertisin(9),swertiajaponin(10)were purified from the seeds of Hovenia dulcis *** structures were confirmed by spectroscopic data analysis and comparison with previous *** compounds were obtained from *** for the first time.

关键词： Hovenia dulcis Thunb chemical constituents Flavonoid c-glycosides

Advances in the development of amorphous solid dispersions:The role of polymeric carriers

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Asian Journal of Pharmaceutical sciences 2023年第4期18卷 45-79页

作者： Jie Zhang Minshan Guo Minqian Luo Ting cai Department of Pharmaceutics School of PharmacyChina Pharmaceutical UniversityNanjing 211198China Department of Pharmaceutical Engineering School of EngineeringChina Pharmaceutical UniversityNanjing 211198China college of biological and chemical Engineering Changsha UniversityChangsha 410022China

Amorphous solid dispersion(ASD)is one of the most effective approaches for delivering poorly soluble *** ASDs,polymeric materials serve as the carriers in which the drugs are dispersed at the molecular *** prepare the solid dispersions,there are many polymers with various physicochemical and thermochemical characteristics available for use in ASD *** selection is of great importance because it influences the stability,solubility and dissolution rates,manufacturing process,and bioavailability of the *** review article provides a comprehensive overview of ASDs from the perspectives of physicochemical characteristics of polymers,formulation designs and preparation ***,considerations of safety and regulatory requirements along with the studies recommended for characterizing and evaluating polymeric carriers are briefly discussed.

关键词： Amorphous solid dispersions Polymeric carriers Stability Dissolution bioavailbility Molecular interactions