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Houttuynia cordata polysaccharides alleviate ulcerative colitis by restoring intestinal homeostasis

Chinese Journal of Natural Medicines 2022年第12期20卷 914-924页

作者： CEN Lifeng YI Tong HAO Yuanzhen SHI Chenchen SHI Xunlong LU Yan CHEN Daofeng ZHU Haiyan department of Biological Medicines&Shanghai Engineering Research Center of immunotherapeutics School of PharmacyFudan UniversityShanghai 200000China Division of Spine Department of OrthopedicsTongji HospitalShanghai 200000China department of Natural Medicine School of PharmacyFudan UniversityShanghai 200000China

Houttuynia cordata is traditionally used as phytoantibiotics for treating lung disease in *** cordata polysaccharides(HCPs)have been reported to alleviate influenza virus-induced intestinal and lung immune injury by regulating the gutlung *** present study aims to investigate the effects and mechanisms of HCPs on ulcerative colitis(UC).Male C57BL/6 mice were induced by dextran sodium sulfate(DSS)to establish the UC animal *** results showed that HCPs significantly reduced the weight loss and the shortening of colon length in colitis mice,and relieved the pathological damage of colon mucosa and inhibited the expression of pro-inflammatory cytokines such as TNF-α,IL-1β,IL-6,*** was suggested that HCPs could significantly improve DSS-induced colitis in *** directly protected intestinal epithelial cells,ameliorated epithelial barrier dysfunction and cell apoptosis,which was also proved in H2O2 stimulated cell apoptosis *** inhibited inflammation in the colon,which was related to suppressing the infiltration of macrophages,inhibiting the expression of pro-inflammatory cytokines and proteins(TLR4,NF-κB),and restoring the dysfunction of Th17 and Treg *** also restored the alteration of intestinal flora induced by DSS,increased the abundance of Firmicutes and Bacteroides,and reduced the abundance of *** study confirmed the protective effect of Houttuynia cordata polysaccharide extracted from traditional Chinese medicine on ulcerative colitis,of which the mechanism was closely related to the maintenance of intestinal homeostasis(intestinal barrier,immune cells,and intestinal bacteria).

关键词： Houttuynia cordata polysaccharide Ulcerative colitis Anti-inflammation Intestinal homeostasis Gut microbiota

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Hedgehog signaling in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment

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Acta Pharmaceutica Sinica B 2021年第3期11卷 609-620页

作者： Jinghui Zhang Jiajun Fan Xian Zeng Mingming Nie Jingyun Luan Yichen Wang Dianwen Ju Kai Yin department of Gastrointestinal Surgery Changhai HospitalSecond Military Medical UniversityShanghai 200433China department of Biological Medicines Fudan University School of PharmacyShanghai 201203China Shanghai Engineering Research Center of immunotherapeutics Shanghai 201203China

The Hedgehog(HH) signaling pathway plays important roles in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment(TME). Aberrant HH signaling activation may accelerate the growth of gastrointestinal tumors and lead to tumor immune tolerance and drug *** interaction between HH signaling and the TME is intimately involved in these processes, for example, tumor growth, tumor immune tolerance, inflammation, and drug resistance. Evidence indicates that inflammatory factors in the TME, such as interleukin 6(IL-6) and interferon-g(IFN-g), macrophages, and T cell-dependent immune responses, play a vital role in tumor growth by affecting the HH signaling pathway. Moreover, inhibition of proliferating cancer-associated fibroblasts(CAFs) and inflammatory factors can normalize the TME by suppressing HH signaling. Furthermore, aberrant HH signaling activation is favorable to both the proliferation of cancer stem cells(CSCs) and the drug resistance of gastrointestinal tumors. This review discusses the current understanding of the role and mechanism of aberrant HH signaling activation in gastrointestinal carcinogenesis, the gastrointestinal TME,tumor immune tolerance and drug resistance and highlights the underlying therapeutic opportunities.

关键词： Hedgehog Carcinogenesis Tumor microenvironment Gastrointestinal cancer Cancer stem cells Drug resistance

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Anticancer potential of Alternanthera sessilis extract on HT-29 human colon cancer cells

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Asian Pacific Journal of Tropical Biomedicine 2018年第8期8卷 394-402页

作者： Sivapragasam Gothai Katyakyini Muniandy Norhaizan Mohd Esa Suresh Kumar Subbiah Palanisamy Arulselvan Laboratory of Vaccines and immunotherapeutics Institute of Bioscience Universiti Putra Malaysia department of Nutrition and Dietetics Faculty of Medicine and Health Sciences Universiti Putra Malaysia department of Medical Microbiology and Parasitology Faculty of Medicine and Health Sciences Universiti Putra Malaysia Muthayammal Centre for advanced Research Muthayammal College of Arts and Science Scigen Research and Innovation Pvt. Ltd. Periyar Technology Business Incubator

Objective: To identify the bioactive extracts from Alternanthera sessilis and investigate its cytotoxicity potential against colon cancer cells, HT-29. Methods: This study examined the effects of three parts(aerial, leaf, stem) of whole plant on HT-29 colon cancer cell lines. Three different extracts from the plant parts were prepared by maceration technique using 80% ethanol. The anticancer activities were determined using MTT, clonogenic, cell motility and AOPI assay. The chemical composition profiling was analyzed by GC-MS. Results: Among three plant part extracts, leaf extract greatly suppressed the growth of colon cancer cells in time and dosage-dependent manner, followed by aerial and stem. The cytotoxicity results were rationalized with clonogenic, cell motility and AO/PI assay, where extract showed the most active activity compared to aerial and stem extracts. GC-MS analysis of leaf extract showed there were various recognized anti-cancer, anti-oxidant and anti-inflammatory compounds. Conclusions: Amid the screened extracts, the leaf extract exhibits the credible cytotoxic, anti-proliferative and apoptotic activity and hence, our findings call for additional research to conclude the active compounds and their mechanisms determining the apoptotic activity.

关键词： Alternanthera sessilis Colorectal cancer Anticancer HT-29 Apoptosis

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Attenuation of lipopolysaccharide-induced neuroinflammatory events in BV-2 microglial cells by Moringa oleifera leaf extract

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Asian Pacific Journal of Tropical Biomedicine 2019年第3期9卷 109-115页

作者： Gothai Sivaprakasam Palanivel Ganesan Katyakyini Muniandy Shin-Young Park Duk-Yeon Cho Joon-So Kim Palanisamy Arulselvan Dong-Kug Choi Laboratory of Vaccines and immunotherapeutics Institute of Bioscience Universiti Putra Malaysia department of Biomedical Chemistry College of Biomedical & Health Science Konkuk University Nanotechnology Research Center Konkuk University Scigen Research and Innovation Pvt.Ltd. Periyar Technology Business Incubator Muthayammal Centre for advanced Research Muthayammal College of Arts and Science department of Biotechnology College of Biomedical and Health Science Konkuk University

Objective: To determine the anti-neuroinflammatory activity of Moringa oleifera leaf extract(MLE) under lipopolysaccharide stimulation of mouse murine microglia BV2 cells in vitro. Methods: The cytotoxicity effect of MLE was investigated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide assay. The inflammatory response of BV-2 cells were induced with lipopolysaccharide. The generation of nitric oxide levels was determined by using Griess assay and the level of pro-inflammatory cytokines(IL-1β, IL-6 and TNF-α) was evaluated by ELISA kit. The expression of iNOS, COX-2 as well as IκB-ααwas carried out by immunoblot analysis. Results: MLE reduced the nitric oxide production in concentration-dependent manner, and maintained the viability of BV-2 microglial cells which indicated absence of toxicity. In addition, MLE repressed the activation of nuclear factor kappa B by arresting the deterioration of IκB-α, consequently resulted in suppression of cytokines expression such as COX-2 and iNOS. Conclusions: MLE inhibitory activities are associated with the inhibition of nuclear factor kappa B transcriptional activity in BV2 microglial cells. Thus MLE may offer a substantial treatment for neuroinflammatory diseases.

关键词： Moringa oleifera leaf extract BV2 microglial cells Neuro-inflammation Pro-inflammatory cytokines NF-κB signaling pathway

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advanced nanomedicines and immunotherapeutics to treat respiratory diseases especially COVID-19 induced thrombosis

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World Journal of Clinical Cases 2024年第16期12卷 2704-2712页

作者： Jie Wu Ying Zheng Li-Na Zhang Cai-Li Gu Wang-Li Chen Min-Qiang Chang department of Respiratory and Oncology 72nd Group Army Hospital of PLAHuzhou 313000Zhejiang ProvinceChina department of Otorhinolaryngology 72^(nd)Group Army Hospital of PLAHuzhou 313000Zhejiang ProvinceChina

Immunotherapy and associated immune regulation strategies gained huge attraction in order to be utilized for treatment and prevention of respiratory *** specifically nanomedicines can be used to regulate host immunity in lungs in the case of respiratory diseases including coronavirus disease 2019(COVID-19)***-19 causes pulmonary embolisms,thus new therapeutic options are required to target thrombosis,as conventional treatment options are either not effective due to the complexity of the immunethrombosis *** this review,we discuss regulation of immune response in respiratory diseases especially *** further discuss thrombosis and provide an overview of some antithrombotic nanoparticles,which can be used to develop nanomedicine against thrombo-inflammation induced by COVID-19 and other respiratory infectious *** also elaborate the importance of immunomodulatory nanomedicines that can block pro-inflammatory signalling pathways,and thus can be recommended to treat respiratory infectious diseases.

关键词： Nanomedicines immunotherapeutics Respiratory diseases COVID-19 Thrombosis

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Antibodies Targeting a Conserved Surface Polysaccharide Are Protective Against a Wide Range of Microbial Pathogens Producing b-1-6-Linked Poly-N-Acetylglucosamine(PNAG)

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Engineering 2024年第7期38卷 69-76页

作者： Xi Lu Guoqing Li Jing Pang Xinyi Yang Colette Cywes-Bentley Xuefu You Gerald B.Pier Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Division of Infectious Diseases Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA

The b-1-6-linked poly-N-acetylglucosamine(PNAG)polymer is a conserved surface polysaccharide produced by many bacteria,fungi,and protozoan(and even filarial)*** wide-ranging expression makes PNAG an attractive target for vaccine development,as it potentially encompasses a broad range of *** progress has been made in discovering important properties of the biology of PNAG expression in recent *** molecular characterization and regulation of operons for the production of PNAG biosynthetic proteins and enzymes have been studied in many *** addition,the physiological function of PNAG has been further ***-based vaccines and PNAG-targeting antibodies have shown great efficacy in preclinical ***,clinical tests for both vaccines and antibodies have been carried out in humans and economically important animals,and the results are *** it is not destined to be a smooth road,we are optimistic about new vaccines and immunotherapeutics targeting PNAG becoming validated and eventually licensed for clinical use against multiple infectious agents.

关键词： Poly-N-acetylglucosamine Conjugate vaccine Monoclonal antibody

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Chinese Medicine Meets Conventional Medicine in Targeting COVID-19 Pathophysiology,Complications and Comorbidities

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Chinese Journal of Integrative Medicine 2022年第7期28卷 627-635页

作者： WANG Shan-shan ZENG Xian WANG Ya-li Zhuoma Dongzhi ZHAO Yu-fen CHEN Yu-zong Qian Xuesen Collaborative Research Center of Astrochemistry and Space Life Sciences Institute of Drug Discovery TechnologyNingbo UniversityNingboZhejiang Province 315211China department of Biological Medicines&Shanghai Engineering Research Center of immunotherapeutics Fudan University School of PharmacyShanghai 201203China Bioinformatics and Drug Design Group Department of PharmacyNational University of Singapore117543Singapore Medical College Tibet UniversityLhasa 850011China department of Chemical Biology College of Chemistry and Chemical Engineeringand The Key Laboratory for Chemical Biology of Fujian ProvinceXiamen UniversityXiamenFujian Province 361005China Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology(Ministry of Education) Department of ChemistryTsinghua UniversityBeijing 102206China

Objective: To investigate how the National Health Commission of China(NHCC)-recommended Chinese medicines(CMs) modulate the major maladjustments of coronavirus disease 2019(COVID-19),particularly the clinically observed complications and comorbidities. Methods: By focusing on the potent targets in common with the conventional medicines, we investigated the mechanisms of 11 NHCC-recommended CMs in the modulation of the major COVID-19 pathophysiology(hyperinflammations, viral replication), complications(pain, headache) and comorbidities(hypertension, obesity, diabetes). The constituent herbs of these CMs and their chemical ingredients were from the Traditional Chinese Medicine Information Database. The experimentally-determined targets and the activity values of the chemical ingredients of these CMs were from the Natural Product Activity and Species Source Database. The approved and clinical trial drugs against these targets were searched from the Therapeutic Target Database and DrugBank Database. Pathways of the targets was obtained from Kyoto Encyclopedia of Genes and Genomes and additional literature search. Results: Overall,9 CMs modulated 6 targets discovered by the COVID-19 target discovery studies, 8 and 11 CMs modulated 8and 6 targets of the approved or clinical trial drugs for the treatment of the major COVID-19 complications and comorbidities, respectively. Conclusion: The coordinated actions of each NHCC-recommended CM against a few targets of the major COVID-19 pathophysiology, complications and comorbidities, partly have common mechanisms with the conventional medicines.

关键词： COVID-19 Chinese medicine target therapeutic mechanism pathophysiology comorbidity

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Depletion of CD25^+CD4^+T cells (Tregs) enhances the HBV-specific CD8^+ T cell response primed by DNA immunization

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World Journal of Gastroenterology 2005年第24期11卷 3772-3777页

作者： Yoshihiro Furuichi Hirotake Tokuyama Satoshi Ueha Makoto Kurachi Fuminori Moriyasu Kazuhiro Kakimi Fourth department of Internal Medicine (Gastroenterology and Hepatology) department of Molecular and Preventive Medicine department of immunotherapeutics (Medinet)

AIM: Persistent hepatitis B virus (HBV) infection is characterized by a weak CD8+ T cell response to HBV. Immunotherapeutic strategies that overcome tolerance and boost these suboptimal responses may facilitate viral clearance in chronically infected individuals. Therefore, we examined whether CD25+CD4+ regulatory T (Treg) cells might be involved in a inhibition of CD8+T cell priming or in the modulation of the magnitude of the'peak' antiviral CD8+ T cell response primed by DNA immunization. METHODS: B10.D2 mice were immunized once with plasmid pCMV-S. Mice received 500 μg of anti-CD25 mAb injected intraperitoneally 3 d before DNA immunization to deplete CD25+ cells. Induction of HBV-specific CD8+ T ceils in peripheral blood mononuclear cells (PBMCs) was measured by S28-39 peptide loaded DimerX staining and their function was analyzed by intracellular IFN-γ ***: DNA immunization induced HBV-specific CD8+ T cells. At the peak T cell response (d 10), 7.1±2.0% of CD8+ T cells were HBV-specific after DNA immunization, whereas 12.7±3.2% of CD8+ T cells were HBV-specific in Treg-depleted mice, suggesting that DNA immunization induced more antigen-specific CD8+ T cells in the absence of CD25+ Treg cells (n = 6, P＜0.05). Similarly, fewer HBVspecific memory T cells were detected in the presence of these cells (1.3±0.4%) in comparison to Treg-depleted mice (2.6±0.9%) on d 30 after DNA immunization (n = 6, P＜0.01). Both IFN-γ production and the avidity of the HBV-specific CD8+ T cell response to antigen were higher in HBV-specific CD8+ T cells induced in the absence of Treg ***: CD25+ Treg cells suppress priming and/or expansion of antigen-specific CD8+ T cells during DNA immunization and the peak CD8+ T cell response is enhanced by depleting this cell population. Furthermore, Treg cells appear to be involved in the contraction phase of the CD8+ T ceil response and may affect the quality of memory T cell pools. The elimination of Treg cells or their i

关键词： CD25^+CD4^+T细胞 CD8^+T细胞乙型肝炎病毒 DNA 免疫机制

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A reporter gene assay for determining the biological activity of therapeutic antibodies targeting TIGIT

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3925-3934页

作者： Zhihao Fu Hongchuan Liu Lan Wang Chuanfei Yu Yalan Yang Meiqing Feng Junzhi Wang Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products National Institutes for Food and Drug ControlBeijing 102629China department of Biological Medicines&Shanghai Engineering Research Center of immunotherapeutics School of PharmacyFudan UniversityShanghai 201203China

T cell immunoglobulin and ITIM domain(TIGIT)is a novel immune checkpoint that has been considered as a target in cancer *** available bioassays for measuring the biological activity of therapeutic antibodies targeting TIGIT are restricted to mechanistic investigations because donor primary T cells are highly ***,we designed a reporter gene assay comprising two cell lines,namely,CHO-CD112-CD3 scFv,which stably expresses CD 112(PVRL2,nectin-2)and a membranebound anti-CD3 single-chain fragment variable(scFv)as the target cell,and Jurkat-NFAT-TIGIT,which stably expresses TIGIT as well as the nuclear factor of activated T-cells(NFAT)response element-controlled luciferase gene,as the effector *** anti-CD3 scFv situated on the target cells activates Jurkat-NFATTIGIT cells through binding and crosslinking CD3 molecules of the effector cell,whereas interactions between CD 112 and TIGIT prevent *** presence of anti-TIGIT mAbs disrupts their interaction,which in turn reverses the inactivation and luciferase *** and validation studies have demonstrated that this assay is superior in terms of specificity,accuracy,linearity,and *** summary,this reliable and effective reporter gene assay may potentially be utilized in lot release control,stability assays,screening,and development of novel TIGIT-targeted therapeutic antibodies.

关键词： TIGIT Therapeutic antibodies Bioactivity determination Reporter gene assay Method validation

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Preliminary nitrite, nitrate and colour analysis of Malaysian edible bird’s nest

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Information Processing in Agriculture 2015年第1期2卷 1-5页

作者： Meei Chien Quek Nyuk Ling Chin Yus Aniza Yusof Sheau Wei Tan Chung Lim Law department of Process and Food Engineering Faculty of EngineeringUniversiti Putra Malaysia43400 UPM SerdangSelangorMalaysia Laboratory of Vaccines and immunotherapeutics Institute of BioscienceUniversiti Putra Malaysia43400 UPM SerdangSelangorMalaysia department of Chemical Engineering Faculty of EngineeringUniversity of NottinghamMalaysia CampusJalan Broga43500 SemenyihSelangorMalaysia

The high nitrite content in edible bird’s nests is a major concern to the local swiftlet *** lowers the price of the edible bird’s nests and it brings severe health hazards to consumers and *** research investigated the nitrite and nitrate contents of eight types of local edible bird’s nests by using ion chromatography system and evaluating its colour using the CIE system in L^*a^*b^**** nitrite content obtained ranged from 5.7 lg/g for the house nests to 843.8 lg/g for the cave *** nitrate content for the house and cave nests was 98.2 lg/g and 36,999.4 lg/g,*** cave nests with darker and redder colour had higher nitrite and nitrate contents than the brighter and more yellow house *** likely suggests that the nitrite and nitrate contents have correlations with edible bird’s nests *** studies suggested that the nitrite content had high correlations with colour parameters,L^*a^*b^*of edible bird’s nests at significant level of P<*** findings suggest that edible bird’s nests’colour may be a useful indicator for measuring nitrite and nitrate contaminations.

关键词： Nitrite Nitrate Colour Ion chromatography Edible bird’s nest

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