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Anti-neuro-inflammatory effects of Nardostachys chinensis in lipopolysaccharide-and lipoteichoic acid-stimulated microglial cells

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Chinese Journal of Natural Medicines 2016年第5期14卷 343-353页

作者： Sun Young Park Young Hun Kim Geuntae Park Bio-IT Fusion Technology Research Institute Pusan National University Department of Nanomaterials Engineering Pusan National University

Excessive microglial cell activation is related to the progression of chronic neuro-inflammatory disorders. Heme oxygenase-1(HO-1) expression mediated by the NFE2-related factor(Nrf-2) pathway is a key regulator of neuro-inflammation. Nardostachys chinensis is used as an anti-malarial, anti-nociceptive, and neurotrophic treatment in traditional Asian medicines. In the present study, we examined the effects of an ethyl acetate extract of N. chinensis(EN) on the anti-neuro-inflammatory effects mediated by HO-1 up-regulation in Salmonella lipopolysaccharide(LPS)- or Staphylococcus aureus lipoteichoic acid(LTA)-stimulated BV2 microglial cells. Our results indicated that EN suppressed pro-inflammatory cytokine production and induced HO-1 transcription and translation through Nrf-2/antioxidant response element(ARE) signaling. EN markedly inhibited LPS- and LTA-induced activation of nuclear factor-kappa B(NF-?B) as well as phosphorylation of mitogen-activated protein kinases(MAPKs) and signal transducer and activator of transcription(STAT). Furthermore, EN protected hippocampal HT22 cells from indirect neuronal toxicity mediated by LPS- and LTA-treated microglial cells. These results suggested that EN impairs LPS- and LTA-induced neuro-inflammatory responses in microglial cells and confers protection against indirect neuronal damage to HT22 cells. In conclusion, our findings indicate that EN could be used as a natural anti-neuro-inflammatory and neuroprotective agent.

关键词： Nardostachys chinensis Anti-inflammation Lipopolysaccharide lipoteichoic acid Heme oxygenase-1

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Effects of lipoteichoic acid induced Delayed Preconditioning on Ischemia-reperfusion Injury in Isolated Rat Hearts

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2003年第3期23卷 230-233页

作者：马世玉向继洲吴基良胡本容 Department of Pharmacology

To explore the potential of lipoteichoic acid (LTA) induced cardioprotection against ischemia-reperfusion (I/R) injury in isolated rat hearts and whether endogenous nitric oxide (NO) participates in the protection, the rats were pretreated with LTA (1 mg/kg, i p ) 24 h before the experiment, and the isolated hearts were subjected to 30 min no-flow normothermic global ischemia and 60 min reperfusion after a 20-min stabilization period by the langendorff method Cardiac functions were evaluated at the end of stabilization, and at 30 min, 60 min of reperfusion The amounts of MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase(LDH) and total NO oxidation products in the coronary effluent were measured spectrophotometrically at the end of reperfusion It was revealed that pretreatment with LTA could significantly improve the recovery of cardiac function, reduce the release of CK-MB and LDH, and increase the concentrations of NO in coronary effluent The protective effects were abrogated by pretreatment of the rats with L-NAME It was concluded that LTA could induce the delayed cardioprotection against I/R injury, and endogenous NO may be involved in the mechanisms

关键词： preconditioning lipoteichoic acid myocardial reperfusion injury nitric oxide

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Concise Synthesis of Lactococcus garvieae lipoteichoic acids Through an Additive-Modulated Preactivation Protocol and the Immunological Studies

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CCS Chemistry 2024年第2期6卷 403-414页

作者： Tianlu Li Tong Li Yue Yang Haoru Zhuang Jianwu Lv Ning Zhou Miaomiao Zhang Fengshan Wang Yiqun Geng Richard R.Schmidt Peng Peng National Glycoengineering Research Center Shandong Key Laboratory of Carbohydrate Chemistry and GlycobiologyNMPA Key Laboratory for Quality Research and Evaluation of Carbohydrate Based MedicineShandong UniversityQingdao 266237 State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050 Department of Chemistry University of KonstanzD-78457 Konstanz

lipoteichoic acids(LTAs)are macroamphiphiles composed of alditol,lipid,phosphate,and carbohydrate *** to their inherent complexity,it is a severe challenge to access LTAs with structural integrity from natural sources for biological or immunological ***,we describe the first total synthesis of Lactococcus garvieae LTA(type II LTA),containing five distinct 1,2-cis gluco/galactopyranosidic linkages,via a novel additive-modulated O-glycosyl trichloroacetimidate preactivation glycosidation *** strategy features(1)high glycosidation yields and excellent 1,2-cis stereoselectivities independent of the donor anomeric configuration,(2)common and inexpensive reagents as promoters and additives,(3)application to standard glycosyl imidate donors without resorting to participating protection,and(4)general application to reactive and less reactive glycosyl ***,via the precise stereocontrolled construction of three galactopyranosidic and two glucopyranosidic bonds on a multigram scale,a series of structurally well-defined LTA molecules were successfully *** evaluation of these type II synthetic LTAs showed a structure–activity relationship in the stimulation of a proinflammatory response.

关键词： 1,2-cis glycosidation stereoselectivity lipoteichoic acid total synthesis additive-modulated trichloroacetimidate glycosidation immune response

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Vigorous,but differential mononuclear cell response of cirrhotic patients to bacterial ligands

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World Journal of Gastroenterology 2011年第10期17卷 1317-1325页

作者： Varenka J Barbero-Becerra María Concepción Gutiérrez-Ruiz Carmen Maldonado-Bernal Félix I Téllez-Avila Roberto Alfaro-Lara Florencia Vargas-Vorácková Department of Gastroenterology Instituto Nacional de Ciencias Médicasy Nutrición Salvador Zubirán Laboratorio de Fisiología Celular División de Ciencias de la Salud Universidad Autónoma Metropolitana-Iztapalapa Unidad de Investigación Médica en Enfermedades Infecciosasy Parasitarias Hospital de Pediatría Unidad de Investigación en Enfermedades Oncológicas Hospital Infantil de México Federico Gómez

AIM： To study the role of gram-positive and gram-negative bacteria in the pathogenesis of liver injury, specifically the activation of inflammatory mediators. METHODS： Peripheral blood mononuclear cells of 20 out-patients were studied, 10 of them with cirrhosis,Peripheral blood mononuclear cells were isolated and exposed to lipopolysaccharide or lipoteichoic acid. CD14, Toll-like receptor 2 and 4 expression was determined by flow cytometry, and tumor necrosis factor （TNF） α, interleukin （1L）-1β, IL-6, IL-12 and IL-10 secretion in su- pernatants was determined by ELISA. RESULTS： Higher CD14, Toll-like receptor 2 and 4 expression was observed in peripheral blood mononudear cells from cirrhotic patients, （P 〈 0.01, P 〈 0.006, P 〈 0.111） respectively. Lipopolysaccharide and lipoteichoic acid induced a further increase in CD14 expression （P 〈 0.111 lipopolysaccharide, P 〈 0.013 lipoteichoic acid）, and a decrease in Toll-like receptor 2 （P 〈 0.008 lipopolysaccharide, P 〈 0.008 lipoteichoic acid） and Toll-like receptor 4 （P 〈 0.008 lipopolysaccharide, P 〈 0.028 li- poteichoic acid） expression. With the exception of TNFα, absolute cytokine secretion of peripheral blood mononuclear cells was lower in cirrhotic patients under nonexposure conditions （P 〈 0.070 IL-6, P 〈 0.009 IL-1]5, P 〈 0.022 IL-12）. Once exposed to lipopolysaccharide or lipoteichoic acid, absolute cytokine secretion of peripheral blood mononuclear cells was similar in cirrhotic and non-cirrhotic patients, determining a more vigorous response in the former （P 〈 0.005 TNFα, IL-1β, IL-6, IL-2 and IL-10 lipopolysaccharide; P 〈 0.037 TNFα; P 〈 0.006 IL-113; P 〈 0.005 IL-6; P 〈 0.007 IL-12; P 〈 0.014 IL-10 lipoteichoic acid）. Response of peripheral blood mononuclear cells was more intense after lipopolysaccharide than after lipoteichoic acid exposure. CONCLUSION： Peripheral blood mononuclear cells of cirrhotic patients are able to respond to a sudden bacterial ligand exposure, particularly lipopolysaccharide, sugg

关键词： Liver cirrhosis Toll-like receptors Cytokines Lipopolysaccharide lipoteichoic acid

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From Environmental Toxicants to Antibacterial Agents:BPA Analogues Selectively Inhibit the Growth of Gram-Positive Bacteria by Disturbing Biosynthesis of the Cell Wall

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Environment & Health 2023年第4期1卷 291-299页

作者： Huiming Cao Zhunjie Li Bolei Chen Jing Wang Zhen Zhou Zhi Li Yun Qian Yong Liang Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances School of Environment and HealthJianghan UniversityWuhan 430056P.R.China Department of Orthopedics General Hospital of Central Theater Command of Chinese People’s Liberation ArmyWuhan 430070P.R.China Department of Biomedical Engineering Florida International UniversityMiamiFlorida 33174United States

Remarkable antibacterial activity of BPA analogues especially for tetrabromobi-sphenol A against Staphylococcus aureus 25923(Sa25923)and methicillin-resistant Staphylococcus aureus(MRSA)has been reported in our previous ***,the toxic effects of the compounds as environmental contaminants on the endocrine system limited their applications in the field of medicine and *** the abuse of antibiotics has led to the emergence of multiple super-resistant bacteria,we considered that structural modifications based on the BPA structure will be available for molecular designing of potential antimicrobial agents without drug *** this study,to further improve the antibacterial activity and reduce the biological toxicity,we performed the computational models to evaluate the binding affinities of BPA analogues to the potential target DltA protein in the biosynthesis of cell wall.A series of synthesized achiral analogues ofα,α,α′-tris(4-hydroxyphenyl)-1-ethyl-4-isopropylbenzene(α,α,α′-TEIB)exhibited low minimum inhibitory concentration against Sa25923 and MRSA(2 or 1μg mL−1).Especially,the analogue A4 did not induce the drug-resistant mutants for all tested Gram-positive bacterial strains and exhibited relatively lower cytotoxicity in HepG2 *** developed classification model based on the light gradient boosting algorithm showed the superior performances on the internal robustness and generalization ability for the ligand-based virtual screening of bisphenol and polyphenol antimicrobial ***,our findings suggest that the molecular structure ofα,α,α′-TEIB is promising as a scaffold,which is expected to achieve a breakthrough in the development of antibiotics which can prevent the invasion of MRSA and other super bacteria.

关键词： Environmental toxicants Antibacterial agents BPA analogues lipoteichoic acid Virtual screening Machine learning

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Construction of an Expression Plasmid pEGFP-N1-boTLR2 for Full-length Bovine TLR2 and Its Expression in HEK293 Cells

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Agricultural Science & Technology 2012年第6期13卷 1194-1197页

作者：王玉明王静萱酒泉职业技术学院甘肃酒泉735000

[Objective] This study aimed to construct a full-length bovine TLR2 expression plasmid pEGFP-N1-boTLR2 and express it in HEK293 cells. [Method] A fulllength coding sequence of bovine TLR2 was cloned by RT-PCR, and ligated into the pMD18-T simple vector and then subcloned into the pEGFP-N1 vector. A recombinant eukaryotic expression plasmid containing the full-length CDS region of bovine TLR2 was constructed and transiently transfected into HEK293 cells. The transfection efficiency and the location of recombinant protein were examined by FCM and confocal microscopy. Then the bovine TLR2 mRNA expression in HEK293/boTLR2 was detected by qRT-PCR. Finally, we analyzed the biological activity through the response that lipoteichoic acid stimulates HEK293/boTLR2 cells. [Result] The full-length TLR2 gene was successfully cloned and ligated into eukaryotic expression vector. The recombinant expression vector expressed bovine TLR2 in HEK293 cells. HEK293/boTLR2 cells produced higher levels of IL-8 secretion than nontransfected HEK293 cells when stimulated with LTA from Staphylococcus aureus. [Conclusion] The established cell model can provide a fast, flexible and convenient means for screening TLR agonists and antagonists, and may also be useful for investigating the interaction between TLR agonists and TLRs.

关键词： Toll-like receptor Bovine HEK293 cells lipoteichoic acid Interleukin-8

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