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Genetic diversity and phylogenetic analysis of EG95 sequences of Echinococcus granulosus:Implications for EG95 vaccine application

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Asian Pacific Journal of Tropical Medicine 2017年第5期10卷 497-500页

作者： Wei Pan De-Sheng Chen Yun-Juan Lu Hui-Wen Xu Wen-Ting Hao Ya-Wen Zhang Su-Ping Qin Kui-Yang Zheng Ren-Xian Tang Jiangsu Key Laboratory of immunity and Metabolism Department of Pathogenic Biology and ImmunologyLaboratory of Infection and ImmunityXuzhou Medical University department of Clinical Medicine Xuzhou Medical University

Objective:To analyse the genetic variability of EG95 sequences and provide guidance for EG95 vaccine application against Echinococcus granulosus(E. granulosus). Methods:We analysed EG95 polymorphism by collecting total 97 different E. granulosus isolates from 12 different host species that originated from 10 different countries. Multiple sequence alignments and the homology were performed by Lasergene 1(DNASTAR Inc.,Madison,WI),and the phylogenetic analysis was performed by using MEGA5.1(CEMI,Tempe,AZ,USA). In addition,linear and conformational epitopes were analysed,including secondary structure,NXT/S glycosylation,fibronectin type ecoⅢ(Fnndary Ⅲ) domain and glycosylphosphatidylinositol anchor signal(GPIanchor). The s structure was predicted by PSIPRED method. Results:Our results indicated that most isolates overall shared 72.6-100% identity in EG95 gene sequence with the published standard EG95 sequence,X90928. However,EG95 gene indeed has polymorphism in different isolates. Phylogenetic analysis showed that different isolates could be divided into three subgroups. Subgroup 1 contained 87 isolates while Subgroup 2 and Subgroup 3 consisted of 3 and 7 isolates,respectively. Four sequences cloned from oncosphere shared a high identity with the parental sequence of the current vaccine,X90928,and they belonged to Subgroup 1. However,in comparison to X90928,several amino acid mutations occurred in most isolates besides oncosphere,which potentially altered the immunodominant linear epitopes,glycosylation sites and secondary structures in EG95 genes. All these variations might change their previous antigenicity and thereby affecting the efficacy of current EG95 vaccine. Conclusions:This study reveals the genetic variability of EG95 sequences in different E. granulosus isolates,and proposed that more vaccination trials would be needed to test the effectiveness of current EG95 vaccine against distinct isolates in different countries.

关键词： Echinococcus granulosus Cystic echinococcosis EG95 Vaccine Genetic diversity

Identification of a CD4 T-cell epitope in the hemagglutinin stalk domain of pandemic H 1N 1 influenza virus and its antigen-driven TCR usage signature in BALB/c mice

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Cellular & Molecular Immunology 2017年第6期14卷 511-520页

作者： I-Na Lu Sophie Farinelle Aurelie Sausy Claude P Muller department of Infection and immunity Luxembourg Institute of Health Esch-sur-Alzette L-4354 Luxembourg

The stalk region of the influenza virus hemagglutinin is relatively well conserved compared with the globular head domain, which makes it a potential target for use as a universal vaccine against influenza. However, the role of CD4 T cells in the hemagglutinin stalk-specific immune response is not clear. Here we identified a mouse CD4 T-cell epitope that encompasses residues HA2113-131 from the hemagglutinin stalk domain after a sub-lethal infection of influenza. In response to stimulation with the identified epitope, splenocytes derived from the infected mice showed significant polyfunctionality as shown by IL-2, TNF-a and IFN-7 production as well as degranulation. Moreover, mice immunized with the peptide corresponding to this CD4 T-cell epitope exhibited interindividual sharing of the CD4 T-cell receptor I~ sequences, and they had a higher survival rate following a challenge with a lethal dose of pandemic H IN 1 influenza virus. Thus, our data demonstrated a crucial role of hemagglutinin stalk-specific CD4 T cells in the host immune resoonse a^ainst influenza virus infection.

关键词： H1N1 hemagglutinin influenza T-cell receptor

Gut microbiota-derived metabolites as key mucosal barrier modulators in obesity

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World Journal of Gastroenterology 2021年第33期27卷 5555-5565页

作者： Yan-Xia Wei Kui-Yang Zheng Yu-Gang Wang Laboratory of Infection and immunity Jiangsu Key Laboratory of Immunity and MetabolismDepartment of Pathogenic Biology and ImmunologyXuzhou Medical UniversityXuzhou 221004Jiangsu ProvinceChina

A significant breakthrough in the field of obesity research was the demonstration that an obese phenotype could be manipulated by modulating the gut *** important next step is to elucidate a human-relevant"map"of microbiota-host interactions that regulate the metabolic health of the *** improved understanding of this crosstalk is a prerequisite for optimizing therapeutic strategies to combat *** mucosal barrier dysfunction is an important contributor to metabolic diseases and has also been found to be involved in a variety of other chronic inflammatory conditions,including cancer,neurodegeneration,and *** mechanistic basis for intestinal barrier dysfunction accompanying metabolic disorders remains poorly *** the molecular and cellular modulators of intestinal barrier function will help devise improved strategies to counteract the detrimental systemic consequences of gut barrier *** in the composition and function of the gut microbiota,i.e.,dysbiosis,are thought to drive obesity-related pathogenesis and may be one of the most important drivers of mucosal barrier *** effects of the microbiota on the host are mediated by microbiota-derived *** this review,we focus on several relatively well-studied microbial metabolites that can influence intestinal mucosal homeostasis and discuss how they might affect metabolic *** design and use of microbes and their metabolites that are locally active in the gut without systemic side effects are promising novel and safe therapeutic modalities for metabolic diseases.

关键词： Obesity Metabolic diseases Microbiota Mucosal homeostasis Gut Microbial metabolites

In search of a pan-coronavirus vaccine:next-generation vaccine design and immune mechanisms

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Cellular & Molecular Immunology 2024年第2期21卷 103-118页

作者： S.Cankat M.U.Demael L.Swadling Division of Infection and immunity Institute of Immunity and TransplantationUniversity College LondonPears BuildingLondon NW32PPUK

Members of the coronaviridae family are endemic to human populations and have caused several epidemics and pandemics in recent *** this review,we will discuss the feasibility of and progress toward the ultimate goal of creating a pan-coronavirus vaccine that can protect against infection and disease by all members of the coronavirus *** will detail the unmet clinical need associated with the continued transmission of SARS-CoV-2,MERS-CoV and the four seasonal coronaviruses(HCoV-OC43,NL63,HKU1 and 229E)in humans and the potential for future zoonotic *** will highlight how first-generation SARS-CoV-2 vaccines and natural history studies have greatly increased our understanding of effective antiviral immunity to coronaviruses and have informed next-generation vaccine *** will then consider the ideal properties of a pan-coronavirus vaccine and propose a blueprint for the type of immunity that may offer ***,we will describe a subset of the diverse technologies and novel approaches being pursued with the goal of developing broadly or universally protective vaccines for coronaviruses.

关键词： Vaccine Coronavirus Cross-reactive immunity Cross-protection Universal

Immune and non-immune responses to hepatitis C virus infection

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World Journal of Gastroenterology 2015年第38期21卷 10739-10748页

作者： Jiaren Sun Ricardo Rajsbaum Min Kyung Yi department of Microbiology and Immunology Institute for Human Infections and ImmunityUniversity of Texas Medical Branch

The host innate and adaptive immune systems are involved in nearly every step of hepatitis C virus(HCV) infection. In patients,the outcome is determined by a series of complex host-virus interactions,whether it is a natural infection or results from clinical intervention. Strong and persistent CD8+ and CD4+ T-cell responses are critical in HCV clearance,as well as cytokineinduced factors that can directly inhibit virus replication. Newly available direct-acting antivirals(DAAs) are very effective in viral clearance in patients. DAA treatment may further result in the down-regulation of programmed death-1,leading to rapid restoration of HCV-specific CD8+ T cell functions. In this review,we focus on recent studies that address the host responses critical for viral clearance and disease resolution. Additional discussion is devoted to the prophylactic vaccine development as well as to current efforts aimed at understanding the host innate responses against HCV infection. Current theories on how the ubiquitin system and interferon-stimulated genes may affect HCV replication are also discussed.

关键词： Hepatitis C virus Hepatitis T cell Direct-acting a

Diversity of Saccharomyces boulardii CNCM I-745 mechanisms of action against intestinal infections

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World Journal of Gastroenterology 2019年第18期25卷 2188-2203页

作者： Dorota Czerucka Patrick Rampall department of Human Health Division of Ecosystems and Immunity Center Scientific of Monaco Center Scientific of Monaco

The yeast Saccharomyces boulardii CNCM I-745 is one of the probiotics recommended for the prevention of antibiotic-associated diarrhea. Studies conducted in vivo and in vitro demonstrated that in the case of infectious diseases there are two potential sites of action of Saccharomyces boulardii CNCM I-745:(1)An action on enteropathogenic microorganisms(adhesion of bacteria and their elimination or an effect on their virulence factors: Toxins, lipopolysaccharide,etc.); and(2) a direct action on the intestinal mucosa(trophic effects, effects on epithelial reconstitution, anti-secretory effects, anti-inflammatory,immunomodulators). Oral administration of Saccharomyces boulardii CNCM I-745 to healthy subjects does not alter their microbiota. However, in the case of diseases associated with the use of antibiotics or chronic diarrhea, Saccharomyces boulardii CNCM I-745 can restore the intestinal microbiota faster. The interaction of Saccharomyces boulardii CNCM I-745 with the innate immune system have been recently demonstrated thus opening up a new therapeutic potential of this yeast in the case of diseases associated with intestinal infections but also other pathologies associated with dysbiosis such as inflammatory diseases.

关键词： Saccharomyces boulardii CNCM I-745 Probiotics Yeast Intestinal infection Mechanism

Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

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Neural Regeneration Research 2025年第1期20卷 41-53页

作者： Alessio Canovai Pete A.Williams department of Biology University of PisaPisaItaly department of Clinical Neuroscience Division of Eye and VisionSt.Erik Eye HospitalKarolinska InstitutetStockholmSweden

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/*** quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary *** quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many *** this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian *** the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and *** quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully ***,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological *** addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

关键词： metabolism mitochondria neurodegenerative disease neuroprotection pyrroloquinoline quinone retinal diseases

Indole-3-propionic Acid-aggravated CCl_(4)-induced Liver Fibrosis via the TGF-β1/Smads Signaling Pathway

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Journal of Clinical and Translational Hepatology 2021年第6期9卷 917-930页

作者： Fei Liu Changfeng Sun Yuanfang Chen Fei Du Yuxiang Yang Gang Wu department of Infectious Diseases Department of TuberculosisLaboratory of Infection and ImmunityThe Affiliated Hospital of Southwest Medical UniversityLuzhouSichuanChina

Background and Aims:The pathogenesis of liver fibrosis involves liver damage,inflammation,oxidative stress,and intestinal ***-3-propionic acid(IPA)has been demonstrated to have antioxidant,anti-inflammatory and anticancer activities,and a role in maintaining gut *** current study aimed to investigate the role of IPA in carbon tetrachloride(CCl4)-induced liver fibrosis and explore the underlying ***:The liver fibrosis model was established in male C57BL/6 mice by intraperitoneal injection of CCl4 twice *** intervention was made orally(20 mg/kg daily).The degree of liver injury and fibrosis were assessed by serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and ***-linked immunosorbent assay and quantitative real-time polymerase chain reaction(qPCR)were used to detect the inflammatory *** malondialdehyde(MDA),glutathione,glutathione peroxidase,superoxide dismutase,and catalase were determined via commercial *** apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling *** expression of mRNA and protein was assayed by qPCR,Western blotting,or immunohistochemical ***:After IPA treatment,the ALT and AST,apoptotic cells,and pro-inflammatory factor levels were enhanced ***,IPA intervention up-regulated the expression of collagen I,α-smooth muscle actin,tissue inhibitor of matrix metalloproteinase-1,matrix metalloproteinase-2,transforming growth factor-β1(TGF-β1),Smad3,and phosphorylated-Smad2/***,IPA intervention did not affect the MDA ***,the administration of IPA remodeled the gut flora ***:IPA aggravated CCl_(4)-induced liver damage and fibrosis by activating HSCs via the TGF-β1/Smads signaling pathway.

关键词： Indole-3-propionic acid CCl_(4) Hepatic fibrosis HSCs TGF-β1

Effects of Xinfeng capsule on the Fas/FasL-mediated apoptotic pathway in patients with rheumatoid arthritis

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Journal of Traditional Chinese Medicine 2018年第4期38卷 601-609页

作者： Sun Yue Liu Jian Cao Yonghe department of Rheumatism immunity The First Affiliated HospitalAnhui University of Chinese Medicine department of Traditional Chinese Medicine The First Affiliated HospitalXinxiang Medical University

OBJECTIVE:To observe the effects of Xinfeng capsule on the apoptosis of peripheral blood CD4+ T lymphocytes and changes in the Fas/Fas L-mediated apoptotic pathway in patients with rheumatoid arthritis(RA).METHODS:A total of 28 RA patients were included in the study;they were randomly divided into the Xinfeng capsule(XFC) group(3 capsules,3 per day)and the leflunomide(LEF) group(1 pellet,once per night).The treatment course in each groups was 12 *** normal control(NC) group consisted of10 healthy *** apoptotic rate was examined using flow ***,Fas L,caspase 8,caspase 3,bcl-2,and bax m RNA were examined using q *** proteins Fas,Fas L,caspase8,and caspase 3 were examined using western ***:After treatment,patients in the two groups all showed some trend of *** activity indexes,joint morning stiffness time,joint swelling/tenderness number,health assessment questionnaire(HAQ) score,RA quality of life(RAQOL) questionnaire,and self-rating anxiety scale(SAS),as well as all apoptotic related indicators were reduced in both groups after treatment with no significant difference between *** the improvement in terms of the self-rating depression scale(SDS) in the XFC group was better than in the LEF *** patients showed lower apoptotic rates in CD4+ T cells,lower bax,Fas,caspase 8,and caspase 3 m RNA,and less protein expression of Fas,caspase 8,and caspase3 than in the NC *** indicators increased after ***,the level of Bcl-2 m RNA was higher in the XFC group than in the NC group before treatment,and it subsequently *** XFC group expressed lower Bcl-2 m RNA than the LEF *** correlations were found between ESR and the apoptotic rate in CD4 + T cells,Fas,and caspase 3;CRP and Fas;and,swollen joint count and Bax,while positive correlations were found between ESR and ***:XFC can regulate the Fas/Fas L system and promote CD4+ T cell apoptosis and thus redu

关键词： Arthritis rheumatoid Fas ligand protein CD4 lymphocyte count Apoptosis Xinfengcapsule