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red wine and green tea reduce H pylori- or VacA-induced gastritis in a mouse model

World Journal of Gastroenterology 2007年第3期13卷 349-354页

作者： Paolo ruggiero Giacomo rossi Francesco Tombola laura Pancotto laura lauretti Giuseppe Del Giudice Mario Zoratti Novartis Vaccines & Diagnostics s.r.l. Research Center SienaItaly Department of Veterinary science University of Camerino Matelica Italy Department of Biomedical sciences University of PadovaItaly CNR Institute of Neuroscience Section for Biomembranes Padova Italy CNr Institute of Neuroscience Section for Biomembranes Padova Italy

AIM: To investigate whether red wine and green tea could exert anti-H pylori or anti-VacA activity in vivo in a mouse model of experimental infection.METHODs: Ethanol-free red wine and green tea concentrates were administered orally as a mixture of the two beverages to H pylori infected mice, or separately to VacA-treated mice. Gastric colonization and gastric in? ammation were quantifi ed by microbiological, histopathological, and immunohistochemical analyses. rEsUlTs: In H pylori -infected mice, the red wine and green tea mixture significantly prevented gastritis and limited the localization of bacteria and VacA to the surface of the gastric epithelium. similarly, both beverages significantly prevented gastric epithelium damage in VacA-treated mice; green tea, but not red wine, also altered the VacA localization in the gastric epithelium. CONClUsION: red wine and green tea are able to prevent H pylori -induced gastric epithelium damage, possibly involving VacA inhibition. This observation supports the possible relevance of diet on the pathological outcome of H pylori infection.

关键词：红葡萄酒绿茶幽门活性饮料组织病理学

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Accurate Diagnosis of sArs-CoV-2 JN.1 by sanger sequencing of receptor-Binding Domain Is Needed for Clinical Evaluation of Its Immune Evasion

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Journal of Biosciences and Medicines 2024年第4期12卷 69-78页

作者： sin Hang lee Milford Molecular diagnostics laboratory Milford CT USA

Background: Omicron JN.1 has become the dominant sArs-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (rBD) and has acquired a hallmark l455s mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The Us CDC used sGTF of TaqPath COVID-19 Combo Kit rT-qPCr as proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥ 6 months should receive an updated COVID-19 vaccine dose. Objective: recommend sanger sequencing instead of proxy indicator to diagnose JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The rNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested rT-PCr, targeting a 398-base segment of the N-gene and a 445-base segment of the rBD of sArs-CoV-2 for amplification. The nested PCr amplicons were sequenced. The DNA sequences were analyzed for amino acid mutations. results: The N-gene sequence showed r203K, G204r and Q229K, the 3 mutations associated with Omicron BA.2.86 (+JN.1). The rBD sequence showed 24 of the 26 known amino acid mutations, including the hallmark l455s mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: sanger sequencing of a 445-base segment of the sArs-CoV-2 rBD is useful for accurate determination of emerging variants. The CDC may consider using sanger sequencing of the rBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.

关键词： Omicron JN.1 sArs-CoV-2 sanger sequencing rBD l455s Mutation Immune Evasion Vaccination Policies CDC

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sanger sequencing for Molecular Diagnosis of sArs-CoV-2 Omicron subvariants and Its Challenges

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Journal of Biosciences and Medicines 2022年第9期10卷 182-223页

作者： sin Hang lee Milford Molecular diagnostics laboratory Milford USA

large population passages of the sArs-CoV-2 in the past two and a half years have allowed the circulating virus to accumulate an increasing number of mutations in its genome. The most recently emerging Omicron subvariants have the highest number of mutations in the spike (s) protein gene and these mutations mainly occur in the receptor-binding domain (rBD) and the N-terminal domain (NTD) of the s gene. The European Centre for Disease Prevention and Control (eCDC) and the World Health Organization (WHO) recommend partial sanger sequencing of the sArs-CoV-2 s gene rBD and NTD on the polymerase chain reaction (PCr)-positive samples in diagnostic laboratories as a practical means of determining the variants of concern to monitor possible increased transmissibility, increased virulence, or reduced effectiveness of vaccines against them. The author’s diagnostic laboratory has implemented the eCDC/WHO recommendation by sequencing a 398-base segment of the N gene for the definitive detection of sArs-CoV-2 in clinical samples, and sequencing a 445-base segment of the rBD and a 490 - 509-base segment of the NTD for variant determination. This paper presents 5 selective cases to illustrate the challenges of using sanger sequencing to diagnose Omicron subvariants when the samples harbor a high level of co-existing minor subvariant sequences with multi-allelic single nucleotide polymorphisms (sNPs) or possible recombinant Omicron subvariants containing a BA.2 rBD and an atypical BA.1 NTD, which can only be detected by using specially designed PCr primers. In addition, sanger sequencing may reveal unclassified subvariants, such as BA.4/BA.5 with l84I mutation in the s gene NTD. The current large-scale surveillance programs using next-generation sequencing (NGs) do not face similar problems because NGs focuses on deriving consensus sequence.

关键词： eCDC WHO sanger sequencing Omicron Variant Minor subvariants BA.4/BA.5 l84I BA.2 Multi-Allelic recombinant

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New Gene Therapy strategies for the Deletion of Exon 44 of Dystrophin Gene Based on Gene Editing by TAlENs

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Open Journal of Medicinal Chemistry 2013年第1期3卷 1-6页

作者： Ping li Yunzhi Pan Alice s. s. li Aijuan sun Jia Zhang H. l. Gao Pierre sirois Kai li Centre Hospitalier de l’Université laval research Center Laval University Quebec Canada Department of Molecular diagnostics and Biopharmaceutics College of Pharmaceutical Science Soochow University Suzhou China DNA sequencing Core laboratory City of Hope National Medical Center Duarte USA Gene Core The Genomics Institute of the Novartis Research Foundation San Diego USA University of Waterloo Waterloo Canada

Duchenne Muscular Dystrophy (DMD) is a severe childhood form of muscular dystrophy. Both the severe form and its milder form of Becker Muscular Dystrophy (BMD) are caused by the mutation of dystrophin gene. Different from some other genetic diseases such as hemophilia that can be treated by replacement therapy, there is no effective therapy for muscular dystrophy in conventional medication. Gene editing technology from the recently developed engineered nucleases such as TAlENs has been successfully employed in genome modification of a variety of species, and will be applied in gene therapy of selected human diseases. The genetic basis of DMD and BMD indicates that DMD is a good target for gene therapy through returning the reading frame of dystrophin gene. Gene therapy strategies described here may apply to many other genetic diseases. Wider application of TAlENs in gene therapy have the potential to dramatically prolong the lifespan of individuals with genetic diseases.

关键词： TAlENs DMD Gene Therapy Exon skipping

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A comprehensive research agenda for zero leprosy

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Infectious Diseases of Poverty 2020年第6期9卷 76-82页

作者： Peter steinmann Courtenay Dusenbury David Addiss Fareed Mirza WCairns s.smith swiss Tropical and Public Health Institute Socinstrasse 574051BaselSwitzerland University of Basel BaselSwitzerland Global Partnership for Zero leprosy Task Force for Global HealthDecaturGAUSA Focus Area for Compassion and Ethics Task Force for Global HealthDecaturGAUSA novartis Foundation BaselSwitzerland University of Aberdeen AberdeenUK

Background: leprosy control achieved dramatic success in the 1980s–1990s with the implementation of short course multidrug therapy,which reduced the global prevalence of leprosy to less than 1 in 10000 population.However,a period of relative stagnation in leprosy control followed this achievement,and only limited further declines in the global number of new cases reported have been achieved over the past decade.Main text In 2016,major stakeholders called for the development of an innovative and comprehensive leprosy strategy aimed at reducing the incidence of leprosy,lowering the burden of disability and discrimination,and interrupting transmission.This led to the establishment of the Global Partnership for Zero leprosy(GPZl)in 2018,with partners aligned around a shared Action Framework committed to achieving the WHO targets by 2030 through national leprosy program capacity-building,resource mobilisation and an enabling research agenda.GPZl convened over 140 experts from more than 20 countries to develop a research agenda to achieve zero leprosy.The result is a detailed research agenda focusing on diagnostics,mapping,digital technology and innovation,disability,epidemiological modelling and investment case,implementation research,stigma,post exposure prophylaxis and transmission,and vaccines.This research agenda is aligned with the research priorities identified by other stakeholders.Conclusions: Developing and achieving consensus on the research agenda for zero leprosy is a significant step forward for the leprosy community.In a next step,research programmes must be developed,with individual components of the research agenda requiring distinct expertise,varying in resource needs,and operating over different timescales.Moving toward zero leprosy now requires partner alignment and new investments at all stages of the research process,from discovery to implementation.

关键词： leprosy Mycobacterium leprae Priorities research strategy Zero leprosy

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