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1.
BMC Microbiol ; 24(1): 114, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575861

RESUMO

BACKGROUND: Diarrhea poses a major threat to bovine calves leading to mortality and economic losses. Among the causes of calf diarrhea, bovine rotavirus is a major etiological agent and may result in dysbiosis of gut microbiota. The current study was designed to investigate the effect of probiotic Limosilactobacillus fermentum (Accession No.OR504458) on the microbial composition of rotavirus-infected calves using 16S metagenomic analysis technique. Screening of rotavirus infection in calves below one month of age was done through clinical signs and Reverse Transcriptase PCR. The healthy calves (n = 10) were taken as control while the infected calves (n = 10) before treatment was designated as diarrheal group were treated with Probiotic for 5 days. All the calves were screened for the presence of rotavirus infection on each day and fecal scoring was done to assess the fecal consistency. Infected calves after treatment were designated as recovered group. Fecal samples from healthy, recovered and diarrheal (infected calves before sampling) were processed for DNA extraction while four samples from each group were processed for 16S metagenomic analysis using Illumina sequencing technique and analyzed via QIIME 2. RESULTS: The results show that Firmicutes were more abundant in the healthy and recovered group than in the diarrheal group. At the same time Proteobacteria was higher in abundance in the diarrheal group. Order Oscillospirales dominated healthy and recovered calves and Enterobacterials dominated the diarrheal group. Alpha diversity indices show that diversity indices based on richness were higher in the healthy group and lower in the diarrheal group while a mixed pattern of clustering between diarrheal and recovered groups samples in PCA plots based on beta diversity indices was observed. CONCLUSION: It is concluded that probiotic Limosilactobacillus Fermentum N-30 ameliorate the dysbiosis caused by rotavirus diarrhea and may be used to prevent diarrhea in pre-weaned calves after further exploration.


Assuntos
Doenças dos Bovinos , Microbioma Gastrointestinal , Limosilactobacillus fermentum , Probióticos , Infecções por Rotavirus , Rotavirus , Animais , Bovinos , Rotavirus/genética , Infecções por Rotavirus/tratamento farmacológico , Infecções por Rotavirus/veterinária , Microbioma Gastrointestinal/genética , Disbiose , Diarreia/tratamento farmacológico , Diarreia/veterinária , Fezes/microbiologia , Probióticos/uso terapêutico , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Bovinos/microbiologia
2.
Virol J ; 20(1): 237, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37848986

RESUMO

BACKGROUND: Aspirin is widely used to treat various clinical symptoms. Evidence suggests that aspirin has antiviral properties, but little is known about its specific effect against rotavirus. METHODS: MA104, Caco-2, and CV-1 cells were infected with rotavirus, and aspirin was added after 12 h. Viral mRNA and titer levels were measured by qRT-PCR and immunofluorescence assays. For in vivo validation, forty specific-pathogen-free SD rats were randomly divided into oral aspirin (ASP) groups and control (NC) groups. 16 S rRNA gene sequencing was performed to identify gut microbiota. After 6 months of continuous ASP/NC administration, the rats were infected with rotavirus. Fecal samples were collected over a 30-day time course, and viral levels were quantified. Proinflammatory cytokines/chemokine levels were measured by ELISA. RESULTS: Aspirin inhibited rotavirus infection in cell lines and in rats. The effects of aspirin on viral replication were associated with the alteration of gut microbiota composition by aspirin, including increased abundance of Firmicutes and decreased abundance of Bacteroidetes after aspirin treatment. Mechanistically, aspirin reduced IL-2 and IL-10 levels, and increased IRF-1 and COX-2 levels. Aspirin blocked rotavirus replication in vitro and in vivo, which might be related to effects on IRF-1, COX-2, chemokines, and gut microbial composition. CONCLUSION: These results indicate that long-term oral aspirin administration reduces rotavirus infection. Intestinal virus infection may be suppressed in elderly patients who take aspirin for a long time. The change of their Gut microbiota may lead to functional disorder of the intestinal tract, which may provide some reference for clinical adjuvant probiotics treatment.


Assuntos
Microbioma Gastrointestinal , Infecções por Rotavirus , Rotavirus , Humanos , Ratos , Animais , Idoso , Rotavirus/genética , Infecções por Rotavirus/tratamento farmacológico , Células CACO-2 , Ciclo-Oxigenase 2 , Ratos Sprague-Dawley , Aspirina/farmacologia , RNA Ribossômico 16S/genética
3.
J Antimicrob Chemother ; 77(12): 3443-3455, 2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-36210599

RESUMO

BACKGROUND: Rotavirus is the foremost cause of acute gastroenteritis among infants in resource-poor countries, causing severe morbidity and mortality. The currently available rotavirus vaccines are effective in reducing severity of the disease but not the infection rates, thus antivirals as an adjunct therapy are needed to reduce the morbidity in children. Viruses rely on host cellular machinery for nearly every step of the replication cycle. Therefore, targeting host factors that are indispensable for virus replication could be a promising strategy. OBJECTIVES: To assess the therapeutic potential of ivermectin and importazole against rotaviruses. METHODS: Antirotaviral activity of importazole and ivermectin was measured against various rotavirus strains (RV-SA11, RV-Wa, RV-A5-13, RV-EW) in vitro and in vivo by quantifying viral protein expression by western blot, analysing viroplasm formation by confocal microscopy, and measuring virus yield by plaque assay. RESULTS: Importin-ß1 and Ran were found to be induced during rotavirus infection. Knocking down importin-ß1 severely impaired rotavirus replication, suggesting a critical role for importin-ß1 in the rotavirus life cycle. In vitro studies revealed that treatment of ivermectin and importazole resulted in reduced synthesis of viral proteins, diminished production of infectious virus particles, and decrease in viroplasm-positive cells. Mechanistic study proved that both drugs perform antirotavirus activity by inhibiting the function of importin-ß1. In vivo investigations in mice also confirmed the antirotavirus potential of importazole and ivermectin at non-toxic doses. Treatments of rotavirus-infected mice with either drug resulted in diminished shedding of viral particles in the stool sample, reduced expression of viral protein in the small intestine and restoration of damaged intestinal villi comapared to untreated infected mice. CONCLUSIONS: The study highlights the potential of importazole and ivermectin as antirotavirus therapeutics.


Assuntos
Infecções por Rotavirus , Rotavirus , Replicação Viral , Animais , Camundongos , Transporte Ativo do Núcleo Celular , Ivermectina/farmacologia , Carioferinas/metabolismo , Rotavirus/efeitos dos fármacos , Rotavirus/fisiologia , Proteínas Virais , Infecções por Rotavirus/tratamento farmacológico
4.
Acta Virol ; 66(2): 166-171, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35766473

RESUMO

Rotavirus is the most important etiological agent of infectious diarrhea in children under 5 years of age with more than 125,000 deaths occurring annually worldwide. The present study aims to determine the effect of curcumin, a natural polyphenol compound, on rotavirus in a cell culture model. The anti-viral activity of curcumin was evaluated by reverse-transcriptase quantitative PCR (RT-qPCR), TCID50, and western blot techniques to assess CC50 in curcumin-treated MA104 cells as well as EC50 and SI within the infected MA104 cell line. Our findings supported that curcumin exerted an inhibitory influence against rotavirus in a dose-dependent manner and decreased the viral titer and VP6 expression by ~99% at a concentration of 30 µM (p Keywords: curcumin; rotavirus; RT-qPCR; in vitro; anti-rotavirus agent.


Assuntos
Curcumina , Infecções por Rotavirus , Rotavirus , Antígenos Virais , Proteínas do Capsídeo , Linhagem Celular , Criança , Pré-Escolar , Curcumina/farmacologia , Humanos , Rotavirus/genética , Infecções por Rotavirus/tratamento farmacológico
5.
Biochem Biophys Res Commun ; 534: 740-746, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33250174

RESUMO

Recombinant viruses expressing fluorescent or luminescent reporter proteins are used to quantitate and visualize viral replication and transmission. Here, we used a split NanoLuc luciferase (NLuc) system comprising large LgBiT and small HiBiT peptide fragments to generate stable reporter rotaviruses (RVs). Reporter RVs expressing NSP1-HiBiT fusion protein were generated by placing an 11 amino acid HiBiT peptide tag at the C-terminus of the intact simian RV NSP1 open reading frame or truncated human RV NSP1 open reading frame. Virus-infected cell lysates exhibited NLuc activity that paralleled virus replication. The antiviral activity of neutralizing antibodies and antiviral reagents against the recombinant HiBiT reporter viruses were monitored by measuring reductions in NLuc expression. These findings demonstrate that the HiBiT reporter RV systems are powerful tools for studying the viral life cycle and pathogenesis, and a robust platform for developing novel antiviral drugs.


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Genes Reporter , Luciferases/genética , Peptídeos/genética , Rotavirus/genética , Animais , Antivirais/farmacologia , Cricetinae , Humanos , Camundongos , Microrganismos Geneticamente Modificados , Testes de Neutralização , Ribavirina/farmacologia , Rotavirus/fisiologia , Infecções por Rotavirus/tratamento farmacológico , Infecções por Rotavirus/virologia , Proteínas não Estruturais Virais/genética , Replicação Viral/genética
6.
BMC Infect Dis ; 21(1): 614, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34182936

RESUMO

BACKGROUND: Despite the global roll-out of rotavirus vaccines (RotaTeq/Rotarix / ROTAVAC/Rotasiil), mortality and morbidity due to group A rotavirus (RVA) remains high in sub-Saharan Africa, causing 104,000 deaths and 600,000 hospitalizations yearly. In Cameroon, Rotarix™ was introduced in March 2014, but, routine laboratory diagnosis of rotavirus infection is not yet a common practice, and vaccine effectiveness studies to determine the impact of vaccine introduction have not been done. Thus, studies examining RVA prevalence post vaccine introduction are needed. The study aim was to determine RVA prevalence in severe diarrhoea cases in Littoral region, Cameroon and investigate the role of other diarrheagenic pathogens in RVA-positive cases. METHODS: We carried out a study among hospitalized children < 5 years of age, presenting with acute gastroenteritis in selected hospitals of the Littoral region of Cameroon, from May 2015 to April 2016. Diarrheic stool samples and socio-demographic data including immunization and breastfeeding status were collected from these participating children. Samples were screened by ELISA (ProSpecT™ Rotavirus) for detection of RVA antigen and by gel-based RT-PCR for detection of the VP6 gene. Co-infection was assessed by multiplexed molecular detection of diarrheal pathogens using the Luminex xTAG GPP assay. RESULTS: The ELISA assay detected RVA antigen in 54.6% (71/130) of specimens, with 45, positive by VP6 RT-PCR and 54, positive using Luminex xTAG GPP. Luminex GPP was able to detect all 45 VP6 RT-PCR positive samples. Co-infections were found in 63.0% (34/54) of Luminex positive RVA infections, with Shigella (35.3%; 12/34) and ETEC (29.4%; 10/34) detected frequently. Of the 71 ELISA positive RVA cases, 57.8% (41/71) were fully vaccinated, receiving two doses of Rotarix. CONCLUSION: This study provides insight on RVA prevalence in Cameroon, which could be useful for post-vaccine epidemiological studies, highlights higher than expected RVA prevalence in vaccinated children hospitalized for diarrhoea and provides the trend of RVA co-infection with other enteric pathogens. RVA genotyping is needed to determine circulating rotavirus genotypes in Cameroon, including those causing disease in vaccinated children.


Assuntos
Antígenos Virais/isolamento & purificação , Proteínas do Capsídeo/isolamento & purificação , Coinfecção/epidemiologia , Diarreia/virologia , Infecções por Rotavirus/epidemiologia , Rotavirus/genética , Bioensaio , Camarões/epidemiologia , Criança Hospitalizada , Pré-Escolar , Coinfecção/diagnóstico , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Masculino , Prevalência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Infecções por Rotavirus/diagnóstico , Infecções por Rotavirus/tratamento farmacológico , Vacinas contra Rotavirus/uso terapêutico , Vacinação , Vacinas Atenuadas/uso terapêutico
7.
Pharm Biol ; 59(1): 1098-1105, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34411493

RESUMO

CONTEXT: 18ß-Glycyrrhetinic acid (18ß-GA), a pentacyclic triterpenoid saponin metabolite of glycyrrhizin, exhibits several biological activities. OBJECTIVE: We investigated the effects of 18ß-GA on MA104 cells infected with rotavirus (RV) and its potential mechanism of action. MATERIALS AND METHODS: Cell Counting Kit-8 was used to assess tissue culture infective dose 50 (TCID50) and 50% cellular cytotoxicity (CC50) concentration. MA104 cells infected with RV SA11 were treated with 18ß-GA (1, 2, 4, and 8 µg/mL, respectively). Cytopathic effects were observed. The virus inhibition rate, concentration for 50% of maximal effect (EC50), and selection index (SI) were calculated. Cell cycle, cell apoptosis, and mRNA and protein expression related to the Fas/FasL pathway were detected. RESULTS: TCID50 of RV SA11 was 10-4.47/100 µL; the CC50 of 18ß-GA on MA104 cells was 86.92 µg/mL. 18ß-GA showed significant antiviral activity; EC50 was 3.14 µg/mL, and SI was 27.68. The ratio of MA104 cells infected with RV SA11 in the G0/G1 phase and the G2/M phase decreased and increased, respectively, after 18ß-GA treatment. 18ß-GA significantly induced apoptosis in the infected cells. Furthermore, after 18ß-GA treatment, the mRNA and protein expression levels of Fas, FasL, caspase 3, and Bcl-2 decreased, whereas the expression levels of Bax increased. DISCUSSION AND CONCLUSIONS: The study demonstrates that 18ß-GA may be a promising candidate for the treatment of RV SA11 infection and provides theoretical support for the clinical development of glycyrrhizic acid compounds for the treatment of RV infection.


Assuntos
Antivirais/farmacologia , Ácido Glicirretínico/análogos & derivados , Infecções por Rotavirus/tratamento farmacológico , Rotavirus/efeitos dos fármacos , Animais , Antivirais/administração & dosagem , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Relação Dose-Resposta a Droga , Proteína Ligante Fas/metabolismo , Ácido Glicirretínico/administração & dosagem , Ácido Glicirretínico/farmacologia , Haplorrinos , RNA Mensageiro/metabolismo , Infecções por Rotavirus/virologia , Receptor fas/metabolismo
8.
Biol Pharm Bull ; 43(6): 932-937, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32475915

RESUMO

Rotavirus (RV) induced diarrhea has been a major reason affecting children healthy under 5 years old especially in developing countries. Although specific vaccines have preventive effects, antiviral therapy is essential for the diarrhea patients. Ziyuglycoside II is a traditional Chinese herb which has been proven to possess anti-virus effects. This study aimed to investigate the roles of Ziyuglycoside II in rotavirus-induced diarrhea and the underlying molecular mechanism. We found that normal MA104 cells treated with RV became swollen and gather together. However, Ziyuglycoside II treatment inhibited cell growth in a dose- and time dependent manner and suppressed RV replication. Moreover, Ziyuglycoside II reversed RV-induced downregulation of anti-inflammatory cytokine interleukin (IL)-10 and upregulation of pro-inflammatory factors, such as interferon-γ (IFN-γ), IL-1ß, IL-6, and tumor necrosis factor (TNF-α). Moreover, Ziyuglycoside II administration and ribavirin blocked toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway both in mRNA and protein level, which was paralleled with immunohistochemical assay. Additionally, Ziyuglycoside II administration improved diarrhea symptoms and decreased diarrhea scores. Ziyuglycoside II and ribavirin inhibited the apoptosis of small intestine epithelial cells induced by RV. Taken together, RV treatment induced diarrhea. Ziyuglycoside II administration inhibited TLR4/NF-κB pathway and inflammatory response and improved RV-induced diarrhea. The inhibitory effects of Ziyuglycoside II on RV-induced diarrhea predicted Ziyuglycoside II may be a promising drug for diarrhea.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antidiarreicos/uso terapêutico , Diarreia/tratamento farmacológico , Infecções por Rotavirus/tratamento farmacológico , Saponinas/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antidiarreicos/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Citocinas/sangue , Diarreia/sangue , Diarreia/etiologia , Diarreia/patologia , Feminino , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Macaca mulatta , Camundongos Endogâmicos BALB C , NF-kappa B/genética , Gravidez , Rotavirus , Infecções por Rotavirus/sangue , Infecções por Rotavirus/complicações , Infecções por Rotavirus/patologia , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética
9.
Ceska Slov Farm ; 69(2): 83-89, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32545987

RESUMO

Rotavirus is one of the most important causative agents of gastroenteritis in both infants and children worldwide, resulting in high mortality and morbidity, mainly in low-income, developing countries. Respective analysis of medical records of newborns hospitalized with acute gastroenteritis showed that the use of α2b-interferon in complex pharmacotherapy was characterized by faster reverse development of clinical manifestations of the disease than in patients who did not receive interferon. In our study, we also aimed to estimate the effectiveness of α2b-interferon supplementation in combination pharmacotherapy of newborns with suspected rotavirus infection. Achievement of this goal was possible with the construction of a decision tree model and determination of decision rules for inclusion of α2b-interferon supplementation into the complex pharmacotherapy. The input parameters of the model were hospitalization days of patients stratified by such signs as the presence or absence of rotavirus infection, as well as the additional inclusion of α2b-interferon supplementation in complex pharmacotherapy. The criterion for prediction and decision-making was global retrospective rotavirus prevalence. The feature of the simulation was that the costs were expressed as relative to each other, which allowed unifying the proposed methodology. Retrospective analysis of the clinical database of Ukrainian newborns with acute diarrhea has proved that the decision of α2b-interferon supplementation as additional treatment could be cost-saving under 7.4 times its lower price.


Assuntos
Interferon alfa-2/economia , Interferon alfa-2/uso terapêutico , Infecções por Rotavirus/tratamento farmacológico , Infecções por Rotavirus/economia , Custos e Análise de Custo , Humanos , Recém-Nascido , Estudos Retrospectivos
10.
BMC Pediatr ; 19(1): 137, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039787

RESUMO

BACKGROUND: Acute gastroenteritis (AGE) is a major cause of pediatric morbidity and mortality around the world. It remains a frequent reason for infection-related admissions to emergency units among all age groups. Following the Syrian refugee crisis and insufficient clean water in our region, we sought to assess the etiological and epidemiological factors pertaining to AGE in South Lebanon. METHODS: In this multi-center cross sectional clinical study, we analyzed the demographic, clinical and laboratory data of 619 Lebanese children from the age of 1 month to 5 years old who were admitted with AGE to pediatrics departments of three tertiary care centers in South Lebanon. RESULTS: Our results revealed that males had a higher incidence of AGE (57.3%) than females. Enteropathogens were identified in 332/619 (53.6%) patients. Single pathogens were found in 294/619 (47.5%) patients, distributed as follows: Entamoeba histolytica in 172/619 (27.8%) patients, rotavirus in 84/619 (13.6%), and adenovirus in 38/619 (6.1%). Mixed co-pathogens were identified in 38/619 (6.1%) patients. Analyzing the clinical manifestations indicated that E. histolytica caused the most severe AGE. In addition, children who received rotavirus vaccine were significantly less prone to rotavirus infection. CONCLUSIONS: Our findings alluded to the high prevalence of E. histolytica and other unidentified enteropathogens as major potential causes of pediatric AGE in hospitalized Lebanese children. This should drive us to widen our diagnostic panel by adopting new diagnostic techniques other than the routinely used ones (particularly specific for the pathogenic amoeba E. histolytica and for the unidentified enteropathogens), and to improve health services in this unfortunate area of the world where insanitary water supplies and lack of personal hygiene represent a major problem.


Assuntos
Antivirais/administração & dosagem , Gastroenterite/epidemiologia , Gastroenterite/virologia , Infecções por Rotavirus/epidemiologia , Estações do Ano , Doença Aguda , Fatores Etários , Criança Hospitalizada , Pré-Escolar , Estudos Transversais , Países em Desenvolvimento , Feminino , Gastroenterite/diagnóstico , Gastroenterite/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Líbano/epidemiologia , Modelos Logísticos , Masculino , Prevalência , Fatores de Risco , Infecções por Rotavirus/diagnóstico , Infecções por Rotavirus/tratamento farmacológico , Índice de Gravidade de Doença , Fatores Sexuais , Fatores Socioeconômicos
11.
Pharmacol Res ; 129: 453-461, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29155014

RESUMO

We previously identified, by a natural-product screen, resveratrol oligomers as inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Here, we report the resveratrol dimer trans-ε-viniferin (TV) and tetramer r-2-viniferin (RV) as inhibitors of the intestinal calcium-activated chloride channel (CaCC) and demonstrate their antisecretory efficacy in a neonatal mouse model of rotaviral diarrhea. Short-circuit measurements show inhibition of CaCC current in the human colonic cell line HT-29 by TV and RV with IC50∼1 and 20µM, respectively. TV primarily inhibited the physiologically relevant, long-term CaCC current following agonist stimulation, without effect on cytoplasmic Ca2+ signaling. TV and RV inhibited short-circuit current in mouse colon as well. In a neonatal mouse model of rotaviral secretory diarrhea produced by oral inoculation with rotavirus, 2µg TV or 11µg RV inhibited secretory diarrhea by >50%, without effect on the rotaviral infection. Our results support the antisecretory efficacy of non-toxic, natural-product resveratrol oligomers for diarrheas produced by CaCC activation. Because these compounds also inhibit the CFTR chloride channel, they may be useful for antisecretory therapy of a wide range of diarrheas.


Assuntos
Benzofuranos/farmacologia , Canais de Cloreto/antagonistas & inibidores , Diarreia/fisiopatologia , Infecções por Rotavirus/fisiopatologia , Estilbenos/farmacologia , Animais , Benzofuranos/uso terapêutico , Canais de Cloreto/fisiologia , Diarreia/tratamento farmacológico , Células HT29 , Humanos , Intestinos/efeitos dos fármacos , Intestinos/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Resveratrol , Rotavirus , Infecções por Rotavirus/tratamento farmacológico , Estilbenos/uso terapêutico
12.
Nanomedicine ; 13(3): 1041-1050, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27890655

RESUMO

Biliary atresia (BA) is a neonatal biliary system disease closely associated with viral infection and bile duct inflammation. Silver nanoparticles (AgNps) have previously revealed antiviral and anti-inflammatory properties. In this study, we have investigated the effects of AgNps in the treatment of the Rhesus rotavirus inoculation induced BA in mice. The morphology, liver histopathology, clinical biochemistry examination, and inflammatory cells were analyzed in BA mice. Results indicated that AgNps could significantly increase the survival rate of BA mice, and reduce jaundice and weight lost and the liver enzymes and bilirubin metabolism clinical parameters were close to the normal levels. Diminished numbers of NK cells were observed by flow cytometry analysis and immunohistochemical staining. Furthermore, the viral load was reduced and transcripts for TGF-ß mRNA were augmented after AgNps treatment. Collectively, our results suggest that AgNps treatment has beneficial effects on the BA mouse model partially through upregulation of TGF-ß.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Atresia Biliar/tratamento farmacológico , Nanopartículas Metálicas/uso terapêutico , Infecções por Rotavirus/tratamento farmacológico , Rotavirus/efeitos dos fármacos , Prata/uso terapêutico , Animais , Ductos Biliares/efeitos dos fármacos , Ductos Biliares/patologia , Atresia Biliar/patologia , Atresia Biliar/virologia , Modelos Animais de Doenças , Feminino , Icterícia/tratamento farmacológico , Icterícia/patologia , Icterícia/virologia , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/virologia , Camundongos Endogâmicos BALB C , Rotavirus/isolamento & purificação , Infecções por Rotavirus/complicações , Infecções por Rotavirus/patologia
13.
BMC Complement Altern Med ; 17(1): 74, 2017 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-28118832

RESUMO

BACKGROUND: Human rotavirus (HRoV) is the leading cause of severe gastroenteritis in infants and children under the age of five years. No specific antiviral drug is available for HRoV infections and the treatment of viral diarrhea is mainly based on rehydration and zinc treatment. In this study, we explored medicinal plants endemic to Turkey flora as a source of anti-HRoV compunds. METHODS: We performed an antiviral screening on Ballota macrodonta, Salvia cryptantha and Rindera lanata extracts by focus reduction assay. The extract with the highest selectivity index (SI) was selected; its antiviral activity was further confirmed against other HRoV strains and by virus yield reduction assay. The step of viral replicative cycle putatively inhibited was investigated by in vitro assays. RESULTS: The methanolic extract of R. lanata (Boraginaceae) showed the most favourable selectivity index. This extract exhibited a dose-dependent inhibitory activity against three different HRoV strains (EC50 values ranging from 5.8 µg/ml to 25.5 µg/ml), but was inactive or barely active against other RNA viruses, namely human rhinovirus and respiratory syncytial virus. The R. lanata extract targets the early steps of HRoV infection, likely by hampering virus penetration into the cells. CONCLUSION: These results make the R. lanata methanolic extract a promising starting material for a bioguided-fractionation aimed at identifying anti-HRoV compounds. Further work is required to isolate the active principle and assess its clinical potential.


Assuntos
Antivirais/análise , Boraginaceae/química , Infecções por Rotavirus/tratamento farmacológico , Rotavirus/efeitos dos fármacos , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Linhagem Celular , Chlorocebus aethiops , Testes de Sensibilidade Microbiana , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
14.
J Biol Chem ; 290(19): 12403-14, 2015 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-25814665

RESUMO

Human rotavirus is the leading cause of severe gastroenteritis in infants and children under the age of 5 years in both developed and developing countries. Human lactadherin, a milk fat globule membrane glycoprotein, inhibits human rotavirus infection in vitro, whereas bovine lactadherin is not active. Moreover, it protects breastfed infants against symptomatic rotavirus infections. To explore the potential antiviral activity of lactadherin sourced by equines, we undertook a proteomic analysis of milk fat globule membrane proteins from donkey milk and elucidated its amino acid sequence. Alignment of the human, bovine, and donkey lactadherin sequences revealed the presence of an Asp-Gly-Glu (DGE) α2ß1 integrin-binding motif in the N-terminal domain of donkey sequence only. Because integrin α2ß1 plays a critical role during early steps of rotavirus host cell adhesion, we tested a minilibrary of donkey lactadherin-derived peptides containing DGE sequence for anti-rotavirus activity. A 20-amino acid peptide containing both DGE and RGD motifs (named pDGE-RGD) showed the greatest activity, and its mechanism of antiviral action was characterized; pDGE-RGD binds to integrin α2ß1 by means of the DGE motif and inhibits rotavirus attachment to the cell surface. These findings suggest the potential anti-rotavirus activity of equine lactadherin and support the feasibility of developing an anti-rotavirus peptide that acts by hindering virus-receptor binding.


Assuntos
Antígenos de Superfície/química , Glicolipídeos/química , Glicoproteínas/química , Glicoproteínas de Membrana/química , Proteínas do Leite/química , Peptídeos/química , Infecções por Rotavirus/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Bovinos , Membrana Celular/metabolismo , Sobrevivência Celular , Equidae , Cavalos , Humanos , Concentração Inibidora 50 , Integrinas/química , Gotículas Lipídicas , Leite , Dados de Sequência Molecular , Proteômica , Rotavirus/metabolismo , Infecções por Rotavirus/tratamento farmacológico , Homologia de Sequência de Aminoácidos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
16.
J Appl Microbiol ; 120(4): 1041-51, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26801008

RESUMO

AIMS: The aim of this study was to determine the antiviral activity of four probiotic metabolites (Lactobacillus and Bifidobacetrium species) against rotavirus in vitro infection monitored by the NSP4 protein production and Ca(2+) release. METHODS AND RESULTS: The antiviral effect of the metabolites was performed due a comparison between a blocking model and an intracelullar model on MA104 cells, with the response of NSP4 production and Ca(2+) liberation measured by flow cytometry. Significant results were obtained with the metabolites of Lactobacillus casei, and Bifidobacterium adolescentis in the reduction of the protein production (P = 0·04 and P = 0·014) and Ca(2+) liberation (P = 0·094 and P = 0·020) in the intracellular model, which suggests a successful antiviral activity against RV infection. CONCLUSIONS: This study demonstrates that probiotic metabolites were able to interfere with the final amount of intracellular NSP4 protein and a successful Ca(2+) regulation, which suggests a new approach to the mechanism exerted by probiotics against the rotavirus infection. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel anti-rotaviral effect exerted by probiotic metabolites monitored by the NSP4 protein during the RV in vitro infection and the effect on the Ca(2+) release is reported; suggesting a reduction on the impact of the infection by decreasing the damage of the cells preventing the electrolyte loss.


Assuntos
Antivirais/farmacologia , Bifidobacterium adolescentis/metabolismo , Glicoproteínas/metabolismo , Lacticaseibacillus casei/metabolismo , Probióticos/farmacologia , Rotavirus/efeitos dos fármacos , Toxinas Biológicas/metabolismo , Proteínas não Estruturais Virais/metabolismo , Animais , Antivirais/uso terapêutico , Linhagem Celular , Macaca mulatta , Probióticos/uso terapêutico , Rotavirus/metabolismo , Infecções por Rotavirus/tratamento farmacológico , Infecções por Rotavirus/virologia
17.
J Trop Pediatr ; 62(6): 464-470, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27283364

RESUMO

OBJECTIVE: To study the efficacy and safety of Saccharomyces boulardii (SB) in acute childhood rotavirus diarrhea. METHODS: Children (3 months to 5 years) with WHO-defined acute watery diarrhea and stool rotavirus positive (n = 60) were randomized into intervention (n = 30) and control (n = 30) groups. The intervention group received SB (500 mg/day) for 5 days. RESULTS: The median duration (hours) of diarrhea was significantly shorter in the intervention group (60 vs. 89; 95% CI: -41.2 to - 16.8). A significantly shorter duration of hospitalization (74 vs. 91; 95% CI: -33.46 to - 0.54) was also seen in the intervention group, but no significant difference was seen for fever and vomiting. There was also no difference between the two groups in the proportion of children requiring parenteral rehydration and persistence of diarrhea lasting beyond day 7. There was no report of any adverse events. CONCLUSIONS: The present trial showed that SB is effective and safe in acute rotavirus diarrhea.


Assuntos
Diarreia Infantil/terapia , Probióticos/uso terapêutico , Infecções por Rotavirus/tratamento farmacológico , Rotavirus/isolamento & purificação , Saccharomyces boulardii , Doença Aguda , Pré-Escolar , Diarreia/tratamento farmacológico , Diarreia Infantil/virologia , Método Duplo-Cego , Esquema de Medicação , Fezes/virologia , Feminino , Hidratação , Humanos , Índia , Lactente , Tempo de Internação , Masculino , Probióticos/efeitos adversos , Infecções por Rotavirus/diagnóstico , Resultado do Tratamento , Vômito
18.
J Formos Med Assoc ; 115(6): 389-94, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27017233

RESUMO

Rotaviruses (RVs) are a major cause of acute gastroenteritis in infants and young children worldwide. These viruses infect the villous epithelium of the small intestine. Part of their replication occurs in cytoplasmic inclusion bodies termed viroplasms. Viroplasms and the lipid droplets (LDs) of cellular organelles are known to interact both physically and functionally. Compounds interfering with the homoeostasis of LDs significantly decrease the production of infectious RV progeny. There is considerable scope for more detailed exploration of such compounds as potential antiviral agents for a disease for which at present no specific therapy exists.


Assuntos
Antivirais/farmacologia , Gastroenterite/tratamento farmacológico , Corpos de Inclusão Viral/metabolismo , Gotículas Lipídicas/metabolismo , Infecções por Rotavirus/tratamento farmacológico , Rotavirus/fisiologia , Replicação Viral/efeitos dos fármacos , Agonistas Adrenérgicos beta/farmacologia , Linhagem Celular , Criança , Gastroenterite/virologia , Humanos , Lactente , Isoproterenol/farmacologia , Gotículas Lipídicas/virologia , Inibidores de Fosfodiesterase/farmacologia , Rotavirus/classificação
19.
Tidsskr Nor Laegeforen ; 136(17): 1458-60, 2016 Sep.
Artigo em Norueguês | MEDLINE | ID: mdl-27686206

RESUMO

BACKGROUND Rotavirus is a common cause of gastroenteritis in children. Neurological manifestations associated with rotavirus infections are well described and range from benign afebrile convulsions to lethal encephalopathy or encephalitis.CASE PRESENTATION We present an uncommon neurological manifestation in a Caucasian child in the course of a rotavirus infection. A 4-year old girl presented with mutism, hypotonia and reduced consciousness. Magnetic resonance imaging revealed diffusion abnormalities in the splenium corpus callosum and bilaterally in the nuclei dentate in the cerebellum. She was diagnosed with rotavirus cerebellitis.INTERPRETATION Her clinical symptoms and the magnetic resonance imaging abnormalities were uncommon and previously described in only a few Caucasian children. The outcome has varied, and some children have shown long term neurological sequela. Treatment with immunoglobulins and corticosteroids has been used in similar cases, but there is no established treatment for this condition.


Assuntos
Doenças Cerebelares/virologia , Infecções por Rotavirus/diagnóstico , Doenças Cerebelares/tratamento farmacológico , Pré-Escolar , Diarreia/virologia , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Mutismo/virologia , Paresia/virologia , Rotavirus/isolamento & purificação , Infecções por Rotavirus/complicações , Infecções por Rotavirus/tratamento farmacológico
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(9): 826-830, 2016 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-27655538

RESUMO

OBJECTIVE: To investigate the therapeutic effects of oral zinc supplement in infants and young children with rotavirus enteritis, and its preventive effects against diarrhea recurrence within 3 months after treatment. METHODS: A total of 103 infants and young children with rotavirus enteritis were randomly divided into zinc supplement group (n=51) and conventional treatment group (n=52). Both groups were equally treated with a comprehensive therapy, besides which the zinc supplement group received zinc gluconate granules for 10 days. The treatment outcomes were examined at 72 hours after treatment, and the time required for the disappearance of positive symptoms and the recovery of injured extra-intestinal organs were determined. In addition, these patients were followed up for 3 months to determine the incidence of diarrhea recurrence after treatment. RESULTS: The overall response rate in the zinc supplement group was significantly higher than that in the conventional treatment group (90% vs 75%; P<0.05). The durations of diarrhea, high fever, and vomiting in the zinc supplement group were significantly shorter than that in the conventional treatment group (P<0.05). In addition, the recurrence rate of diarrhea and the incidence of severe diarrhea within 3 months after treatment in the zinc supplement group were significantly lower than in the conventional treatment group (P<0.05). CONCLUSIONS: Oral zinc supplement as adjunctive therapy is effective in treating infants and young children with rotavirus enteritis, and reducing the incidence and severity of diarrhea recurrence in the subsequent 3 months.


Assuntos
Enterite/tratamento farmacológico , Infecções por Rotavirus/tratamento farmacológico , Zinco/administração & dosagem , Pré-Escolar , Suplementos Nutricionais , Feminino , Humanos , Lactente , Masculino , Recidiva
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