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In the era of rapid mRNA-based vaccines:Why is there no effective hepatitis C virus vaccine yet?

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World Journal of Hepatology 2021年第10期13卷 1234-1268页

作者： Natalia Echeverria Victoria Comas Fabian Aldunate Paula Perbolianachis Pilar Moreno Juan Cristina laboratorio de virologia molecular Centro de Investigaciones NuclearesFacultad de CienciasUniversidad de la RepublicaMontevideo 11400Uruguay laboratorio de Evolucion Experimental de Virus Institut PasteurMontevideo 11400Uruguay departamento de desarrollo Biotecnologico Instituto de HigieneFacultad de MedicinaUniversidad de la RepublicaMontevideo 11600Uruguay

Hepatitis C virus(HCV)is responsible for no less than 71 million people chronically infected and is one of the most frequent indications for liver transplanta-tion *** direct-acting antiviral therapies fuel optimism in controlling HCV infections,there are several obstacles regarding treatment accessibility and reinfection continues to remain a ***,the majority of new HCV infections in developed countries occur in people who inject drugs and are more plausible to get *** achieve global epidemic control of this virus the development of an effective prophylactic or therapeutic vaccine becomes a *** coronavirus disease 19(COVID-19)pandemic led to auspicious vaccine development against severe acute respiratory syndrome coronavirus-2(SARSCoV-2)virus,which has renewed interest on fighting HCV epidemic with *** aim of this review is to highlight the current situation of HCV vaccine candidates designed to prevent and/or to reduce HCV infectious cases and their *** will emphasize on some of the crossroads encountered during vaccine development against this insidious virus,together with some key aspects of HCV immunology which have,so far,ham-pered the progress in this *** main focus will be on nucleic acid-based as well as recombinant viral vector-based vaccine candidates as the most novel vaccine approaches,some of which have been recently and successfully employed for SARS-CoV-2 ***,some ideas will be presented on which methods to explore for the design of live-attenuated vaccines against HCV.

关键词： Hepatitis C virus Vaccine candidates Nucleic acid-based vaccines Recombinant vector-based vaccines Challenges COVID-19

Current status of the genetic susceptibility in attenuated adenomatous polyposis

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World Journal of Gastrointestinal Oncology 2019年第12期11卷 1101-1114页

作者： Víctor Lorca Pilar Garre laboratorio de Oncología molecular Grupo de Investigación Clínica y Traslacional en OncologíaHospital Clínico San CarlosMadrid 28040Spain laboratorio de Oncología molecular Servicio de OncologíaHospital Clínico San CarlosMadrid 28040Spain

Adenomatous polyposis(AP)is classified according to cumulative adenoma number in classical AP(CAP)and attenuated AP(AAP).Genetic susceptibility is the major risk factor in CAP due to mutations in the known high predisposition genes APC and ***,the contribution of genetic susceptibility to AAP is lower and less *** predisposition genes have been recently proposed,and some of them have been validated,but their scarcity hinders accurate risk estimations and prevalence *** is a heterogeneous condition in terms of severity,clinical features and ***,clinicians do not have strong discriminating criteria for the recommendation of the genetic study of known predisposition genes,and the detection rate is *** and knowledge of new AAP high predisposition genes are of great importance to offer accurate genetic counseling to the patient and family *** review aims to update the genetic knowledge of AAP,and to expound the difficulties involved in the genetic analysis of a highly heterogeneous condition such as AAP.

关键词： Attenuated adenomatous polyposis Genetic susceptibility High predisposition gene Genetic heterogeneity Colorectal cancer

Fruiting increases total content of flavonoids and antiproliferative effects of Cereus jamacaru D.C. cladodes in sarcoma 180 cells in vitro

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Asian Pacific Journal of Tropical Biomedicine 2019年第2期9卷 66-72页

作者： Jean Carlos Vencioneck Dutra Juda Ben-Hur de Oliveira Vanessa Silva dos Santos Paula Roberta Costalonga Pereira Jean Moises Ferreira Maria do Carmo Pimentel Batitucci laboratorio de Genetica Vegetal e Toxicologica Departamento de Ciencias BiologicasUniversidade Federal do Espirito Santo laboratorio de Biologia molecular e Expressao Genica Departamento de Ciências BiologicasUniversidade Federal de Alagoas

Objective: To evaluate the influence of fruiting phenological stage on total flavonoid content, antioxidant activity, and antiproliferative effects of Cereus jamacaru(C. jamacaru)(mandacaru) cladodes and fruit. Methods: Fruit and cladodes at vegetative and fruiting stage of C. jamacaru were collected. The fruit was dissected and bark, pulp, and seeds were separated. Vegetative and fruiting cladodes, together with bark, pulp, and seeds were used to obtain five hydroalcoholic extracts. The extracts were investigated for total flavonoid content, using AlCl3 colorimetric method, antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical scavenging capacity and Fe^(2+) ion chelating activity, and in vitro antiproliferative effects(sarcoma 180 cells) by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2 H-tetrazolium bromide assay. Results: The extract of C. jamacaru cladodes at the fruiting stage showed higher flavonoid content compared to the other extracts. Seed extracts showed the highest antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) assays, and the extract of cladodes at vegetative stage showed better antioxidant activity in Fe^(2+) ion chelating activity. The extract of fruiting cladodes promoted higher antiproliferative effects compared to the other extracts. Conclusions: These findings suggest that fruiting increases the content of flavonoids and antiproliferative effects of C. jamacaru cladodes. Data reinforce the potential use of C. jamacaru cladodes and fruits as natural antioxidants and potent anticancer agent.

关键词： Mandacaru Flavonoid content DPPH ABTS Fe^(2+) ion chelating activity MTT assay Sarcoma 180 cells

A PCR and RFLP-based molecular diagnostic algorithm for visceral leishmaniasis

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Asian Pacific Journal of Tropical Medicine 2020年第2期13卷 62-70页

作者： Natalia Souza de Godoy Manoel Sebastiao da Costa Lima-Junior Jose Angelo Lauletta Lindoso Vera Lucia Pereira-Chioccola Thelma Suely Okay Lucia Maria Almeida Braz laboratorio de Parasitologia Médica Departamento de Moléstias Infecciosas e Parasitárias do Hospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de Sao PauloSao PauloBrazil laboratorio de Imunopatologia e Biologia molecular-Instituto Aggeu Magalhaes/IAM-FIOCRUZ RecifeBrazil laboratorio de Soroepidemiologia e Imunobiologia-FMUSP Sao PauloBrazil laboratorio de Biologia molecular de Parasitas e Fungos-Instituto Adolfo Lutz Sao PauloBrazil laboratorio de Parasitologia-Instituto de Medicina Tropical de Sao Paulo-USP Sao PauloBrazil

Objective:To determine an algorithm for molecular diagnosis of visceral leishmaniasis(VL)by kinetoplast DNA(kDNA)(RV1/RV2)and internal transcriber spacer(ITS1)(LITSR/L5.8 S)polymerase chain reaction(PCR),complemented by ITS 1 PCR restriction fragment length polymorphism(RFLP),using peripheral blood or bone marrow aspirate from patients with suspected ***:Biological samples were submitted to the gold standard for the diagnosis of VL and molecular diagnosis represented by ITS 1 PCR,kDNA PCR,and ITS 1 PCR *** samples were obtained from seven groups:groupⅠ,82 samples from patients with confirmed VL;groupⅡ,16 samples from patients under treatment for VL;groupⅢ,14 samples from dogs with canine visceral leishmaniasis(CVL);groupⅣ,a pool of six experimentally infected sandflies(Lutzomya longipalpis);group V,18 samples from patients with confirmed tegumentary leishmaniasis(TL)and groupsⅥandⅦwere from control groups without ***:The following gold standard and molecular examination results were obtained for each of the seven groups:groupⅠ:parasitologic and immunochromatographic tests showed a sensitivity of 76.3%(61 of 80)and 68.8%(55 of 80),respectively,and a sensitivity of 97.6%(80 of 82)and 92.7%(76 of 82)by ITS1 and kDNA PCR,*** ITS1 PCR RFLP(HaeⅢ)analysis of the 80 positive samples,52.5%(42 of 80)generated three fragments of 180,70,and 50 bp,corresponding to the pattern of Leishmania infantum infantum;groupⅡ:negative for the parasitologic methods and positive for IrK39(100%,16 of 16),presented 12.5%(2 of 16)of positivity by ITS 1 PCR and 25.0%(4 of 16)by kDNA PCR;groupⅢ:positive in the parasitologic and serologic tests(100%,14 of 14),presented 85.7%(12 of 14)of positivity by ITS1 PCR and kDNA ***1 PCR RFLP showed that 83.3%(10 of 12)of the canine samples contained parasites with profiles similar to ***;groupⅣpresented amplifications by ITS1 PCR and kDNA ***1 PCR products were analyzed by RFLP,generating a profile similar to

关键词： Leishmania infantum molecular diagnosis Visceral leishmaniasis PCR RFLP

Influence of dissolved organic matter character on mercury incorporation by planktonic organisms: An experimental study using oligotrophic water from Patagonian lakes

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Journal of Environmental Sciences 2013年第10期25卷 1980-1991页

作者： María C.Diéguez Claudia P.Queimalios Sergio Ribeiro Guevara Mark Marvin-DiPasquale Carolina Soto Crdenas María A.Arribre laboratorio de Fotobiología INIBIOMA CONICET-UNComahue laboratorio de Fotobiolog INIBIOMA CONICET-UNComahue laboratorio de Anlisis por Activación Neutrónica Centro Atómico Bariloche CNEA United States Geological Survey laboratorio de Anlisis por Activacio Neutrónica Centro Atómico Bariloche CNEA

Ligands present in dissolved organic matter （DOM） form complexes with inorganic divalent mercury （Hg^2＋） affecting its bioavailability in pelagic food webs. This investigation addresses the influence of a natural gradient of DOM present in Patagonian lakes on the bioaccumulation of Hg^2＋（the prevailing mercury species in the water column of these lakes） by the algae Cryptomonas erosa and the zooplankters Brachionus calyciflorus and Boeckella antiqua. Hg^2＋ accumulation was studied through laboratory experiments using natural water of four oligotrophic Patagonian lakes amended with^197Hg^2＋. The bioavailability of Hg^2＋ was affected by the concentration and character of DOM. The entrance of Hg^2＋ into pelagic food webs occurs mostly through passive and active accumulation. The incorporation of Hg^2＋ by Cryptomonas, up to 27% of the Hg^2＋ amended, was found to be rapid and dominated by passive adsorption, and was greatest when low molecular weight compounds with protein-like or small phenolic signatures prevailed in the DOM. Conversely, high molecular weight compounds with a humic or fulvic signature kept Hg^2＋ in the dissolved phase, resulting in the lowest Hg^2＋ accumulation in this algae. In Brachionus and Boeckella the direct incorporation of Hg from the aqueous phase was up to 3% of the Hg^2＋ amended. The dietary incorporation of Hg^2＋ by Boeckella exceeded the direct absorption of this metal in natural water, and was remarkably similar to the Hg^2＋ adsorbed in their prey. Overall, DOM concentration and character affected the adsorption of Hg^2＋ by algae through competitive binding, while the incorporation of Hg^2＋ into the zooplankton was dominated by trophic or dietary transfer.

关键词： mercury dissolved organic matter plankton mercury incorporation Patagonian lakes Argentina

Role of gene polymorphisms in gastric cancer and its precursor lesions:Current knowledge and perspectives in Latin American countries

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World Journal of Gastroenterology 2014年第16期20卷 4503-4515页

作者： Miguel Angel Chiurillo laboratorio de Genética molecular "Dr.Jorge Yunis-Turbay" Decanato de Ciencias de la SaludUniversidad Centroccidental Lisandro AlvaradoBarquisimeto 3001Venezuela

Latin America shows one of the highest incidence rates of gastric cancer in the world,with variations in mortality rates among nations or even within countries belonging to this *** cancer is the result of a multifactorial complex process,for which a multistep model of carcinogenesis is currently *** to the infection with Helicobacter pylori,that plays a major role,environmental factors as well as genetic susceptibility factors are significant players at different stages in the gastric cancer *** differences in population origin,demographic structure,socio-economic development,and the impact of globalization lifestyles experienced in Latin America in the last decades,all together offer opportunities for studying in this context the influence of genetic polymorphisms in the susceptibility to gastric *** aim of this article is to discuss current trends on gastric cancer in Latin American countries and to review the available published information about studies of association of gene polymorphisms involved in gastric cancer susceptibility from this region of the world.A total of 40 genes or genomic regions and69 genetic variants,58%representing markers involved in inflammatory response,have been used in a number of studies in which predominates a low number of individuals(cases and controls)*** of IL-1B(-511 C/T,14 studies;-31 T/C,10 studies)and IL-1RN(variable number of tandem repeats,17 studies)are the most represented ones in the reviewed *** genetic variants recently evaluated in large metaanalyses and associated with gastric cancer risk were also analyzed in a few studies[e.g.,prostate stem cell antigen(PSCA),CDH1,Survivin].Further and better analysis centered in gene polymorphisms linked to other covariates,epidemiological studies and the information provided by meta-analyses and genome-wide association studies should help to improve our understanding of gastric cancer etiology in order to d

关键词： Latin America Gastric cancer Precancerous lesions Gene polymorphisms Single nucleotide polymorphisms

Apomorphine effects on the hippocampus

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Neural Regeneration Research 2018年第12期13卷 2064-2066页

作者： Luis Enrique Arroyo-García Antonio Rodríguez-Moreno Gonzalo Flores laboratorio de Neuropsiquiatria Instituto de Fisiologia Benemerita Universidad Autenoma de Puebla Puebla Mexico laboratorio de Neurociencia Celular y Plasticidad Universidad Pablo de Olavide Sevilla Spain

Apomorphine is a non-specific dopamine receptor agonist that has been used in the treatment of some diseases and mental disorders. Its use has particularly well documented in Parkinson＇s disease（PD）. The dopaminergic agonists like apomorphine are related to oxidative processes that could induce cell damage and the functional impairment of some structures in the brain. However, most information about apomorphine in literature is focused on the improvement of the motor problems characteristic of PD, but little is known about the effects on cognitive behaviors and brain structures indirectly related to motor function. The presence of dopaminergic receptors in the hippocampus has recently been discovered, in connection with cognitive behaviors like learning and memory, these receptors are needed in neuronal plasticity. There has been a growing interest to know if this structure could be compromised by the effect of apomorphine and elucidate if part of the cognitive impairment present in the PD is due to the effect of apomorphine. In this mini-review, we summarized how apomorphine has been used since its creation, we discuss the latest information about its effect on the hippocampus and also the future perspectives to fully understand the effects of this compound.

关键词： dopamine receptor apomorphine hippocampus learning and memory plasticity dendritic length oxidative stress Parkinson's disease

Antibacterial enhancement of antibiotic activity by Enterolobium contortisiliquum(Vell.)Morong

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Asian Pacific Journal of Tropical Biomedicine 2017年第10期7卷 945-949页

作者： Zildene de Sousa Silveira Nair Silva Macêdo Thiago Sampaio de Freitas Ana Raquel Pereira da Silva Joycy Francely Sampaio dos Santos Maria Flaviana Bezerra Morais-Braga José Galberto Martins da Costa Raimundo Nonato Pereira Teixeira Jean Paul Kamdem Henrique Douglas Melo Coutinho Francisco Assis Bezerra da Cunha laboratorio de Bioprospeccao do Semioarido Universidade Regional do CaririCratoBrazil laboratorio de Microbiologia e Biologia molecular Universidade Regional do CaririCratoBrazil laboratorio de Pesquisas de Produtos Naturais Universidade Regional do CaririCratoBrazil departamento de Ciencias biologicas Universidade Regional do Cariri-URCACratoCEP:63105-000Brazil Programa de Pos-graduacao em Bioprospeccao molecular Universidade Regional do Cariri–URCACratoBrazil

Objective: To identify the main chemical classes of compounds from aqueous extract of Enterolobium contortisiliquum(E. contortisiliquum) seed bark and to evaluate its antibacterial activity, as well as its potential to increase the activity of antibiotics against strains of Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia ***: Different classes of compounds in the aqueous extract of E. contortisiliquum were evaluated based on the visual changes in the coloration and the formation of precipitate after the addition of specific reagents. The antibacterial activity of the extract and its potential to increase of antibiotic activity of antibiotics drugs, gentamicin and norfloxacin was determined by using the microdilution ***: Our results demonstrated that the following secondary metabolites were presented in E. contortisiliquum seed bark: flavones, flavonols, xanthones, flavononols,chalcones, aurones, flavones and catechins. The extract itself had very low antibacterial activity against all bacterial strains tested(MIC ≥ 1024 μg/m L), but there was an increase in the antibiotic activity of gentamicin and norfloxacin when combined in the subinhibitory concentration(i.e., MIC/8).Conclusions: Our data suggests that E. contortisiliquum seed bark may be an alternative source for new drugs with the potential to increase antibiotic activity against different strains of bacteria.

关键词： Antibiotic activity Enhancement Synergism Chemical compounds Bioactivity

Endophytic fungi alter sucking bug responses to cotton reproductive structures

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Insect Science 2017年第6期24卷 1003-1014页

作者： Gregory A. Sword Ashley Tessnow Maria Julissa Ek-Ramos department of Entomology Texas A&M University College Station Texas USA Ecology and Evolutionary Biology Interdisciplinary Program Texas A&M University College Station Texas USA laboratorio de Inmunologia y virologia Facultad de Ciencias BiolSgicas Universidad Autonoma de Nuevo Leon San Nicolas de los Garza Nuevo Leon Mexico

All plants including cotton host a wide range of microorganisms as endophytes. There is a growing appreciation of the prevalence, ecological significance and management potential of facultative fungal endophytes in protecting plants from pests, pathogens and environmental stressors. Hemipteran sucking bugs have emerged as major pests across the U.S. cotton belt, reducing yields directly by feeding on developing reproductive structures and indirectly by vectoring plant pathogens. We used no-choice and simultaneous choice assays to examine the host selection behavior of western tarnished plant bugs （Lygus hesperus） and southern green stink bugs （Nezara viridula） in response to developing flower buds and fruits from cotton plants colonized by 1 of 2 candidate beneficial fungal endophytes, Phialemonium inflatum or Beauveria bassiana. Both insect species exhibited strong negative responses to flower buds （L. hesperus） and fruits （N. viridula） from plants that had been colonized by candidate endophytic fungi relative to control plants under both no-choice and choice conditions. Behavioral responses of both species indicated that the insects were deterred prior to contact with plant tissues from endophyte-colonized plants, suggesting a putative role for volatile compounds in mediating the negative response. Our results highlight the role of fungal endophytes as plant mutualists that can have positive effects on plant resistance to pests.

关键词： behavior endophyte fungi Hemiptera mutualism sucking bug