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INTRODUCTION AND OBJECTIVES: Liver fibrosis remains a complication derived from a chronic Hepatitis C Virus (HCV) infection even when it is resolved, and no liver antifibrotic drug has been approved. Molecular mechanisms on hepatocytes and activation of hepatic stellate cells (HSCs) play a central role in liver fibrogenesis. To elucidate molecular mechanisms, it is important to analyze pathway regulation during HSC activation and HCV infection. MATERIALS AND METHODS: We evaluate the fibrosis-associated molecular mechanisms during a co-culture of human HSCs (LX2), with human hepatocytes (Huh7) that express HCV NS5A or Core protein. We evaluated LX2 activation induced by HCV NS5A or Core expression in Huh7 cells during co-culture. We determined a fibrosis-associated gene expression profile in Huh7 that expresses NS5A or Core proteins during the co-culture with LX2. RESULTS: We observed that NS5A induced 8.3-, 6.7- and 4-fold changes and that Core induced 6.5-, 1.8-, and 6.2-fold changes in the collagen1, TGFß1, and timp1 gene expression, respectively, in LX2 co-cultured with transfected Huh7. In addition, NS5A induced the expression of 30 genes while Core induced 41 genes and reduced the expression of 30 genes related to fibrosis in Huh7 cells during the co-culture with LX2, compared to control. The molecular pathways enriched from the gene expression profile were involved in TGFB signaling and the organization of extracellular matrix. CONCLUSIONS: We demonstrated that HCV NS5A and Core protein expression regulate LX2 activation. NS5A and Core-induced LX2 activation, in turn, regulates diverse fibrosis-related gene expression at different levels in Huh7, which can be further analyzed as potential antifibrotic targets during HCV infection.
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The Cucurbitaceae family is an extensive group of fruits and vegetables that exhibit common characteristics; for example, they are farmed on a global scale and exhibit a wide range of applications, including fresh consumption and use in various food and beverage products. As is frequent, many species or genera share a common name, and this can lead to some confusion when looking for information about a specific variety. In this review, we describe the findings about the biological activity, like antibacterial, antiviral, antidiabetic, and anticancer properties, of two genera of this family, Cucumis and Momordica, which have been characterized and evaluated in several research studies and regarding which information is readily accessible. Those activities rely on the various physicochemical qualities and nutritional content of each variety, including factors like ß-carotene and polyphenols, among others. The goal of this review is to provide a rapid search for each activity examined in the literature, enabling future research on their potential uses in functional foods and nutraceutical supplements.
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Hepatocellular carcinoma (HCC) is the most common liver cancer. It is highly lethal and has high recurrence. Death among HCC patients occur mainly due to tumor progression, recurrence, metastasis, and chemoresistance. Cancer stem cells (CSCs) are cell subpopulations within the tumor that promote invasion, recurrence, metastasis, and drug resistance. Hepatic stellate cells (HSCs) are important components of the tumor microenvironment (TME) responsible for primary secretory ECM proteins during liver injury and inflammation. These cells promote fibrogenesis, infiltrate the tumor stroma, and contribute to HCC development. Interactions between HSC and CSC and their microenvironment help promote carcinogenesis through different mechanisms. This review summarizes the roles of CSCs and HSCs in establishing the TME in primary liver tumors and describes their involvement in HCC chemoresistance.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Linhagem Celular Tumoral , Movimento Celular , Células-Tronco Neoplásicas/metabolismo , Microambiente TumoralRESUMO
SARS-CoV-2 variants of concern (VOCs) or of interest (VOIs) causing vaccine breakthrough infections pose an increased risk to worldwide public health. An observational case-control study was performed of SARS-CoV-2 vaccine breakthrough infections in hospitalized or ambulatory patients in Monterrey, Mexico, from April through August 2021. Vaccination breakthrough was defined as a SARS-CoV-2 infection that occurred any time after 7 days of inoculation with partial (e.g., first dose of two-dose vaccines) or complete immunization (e.g., second dose of two-dose vaccines or single-dose vaccine, accordingly). Case group patients (n = 53) had partial or complete vaccination schemes with CanSino (45%), Sinovac (19%), Pfizer/BioNTech (15%), and AstraZeneca/Oxford (15%). CanSino was administered most frequently in ambulatory patients (p < 0.01). The control group (n = 19) received no COVID-19 vaccines. Among SARS-CoV-2 variants detected by whole-genome sequencing, VOC Delta B.1.617.2 predominated in vaccinated ambulatory patients (p < 0.01) and AY.4 in hospitalized patients (p = 0.04); VOI Mu B.1.621 was detected in four (7.55%) vaccinated patients. SARS-CoV-2 breakthrough infections in our hospital occurred mostly in patients vaccinated with CanSino due to the higher prevalence of CanSino vaccine administration in our population. These patients developed mild COVID-19 symptoms not requiring hospitalization. The significance of this study lies on the detection of SARS-CoV-2 variants compromising the efficacy of local immunization therapies in Monterrey, Mexico.
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COVID-19/virologia , SARS-CoV-2/isolamento & purificação , Adulto , Idoso , COVID-19/epidemiologia , Vacinas contra COVID-19 , Estudos de Casos e Controles , Feminino , Hospitalização , Hospitais Universitários , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Filogenia , Prevalência , SARS-CoV-2/classificação , SARS-CoV-2/genética , Vacinação , Eficácia de Vacinas , Sequenciamento Completo do GenomaRESUMO
Little information is available regarding the pathogens that cause diarrhea in hospitalized patients who also have various clinical problems. The purpose of this study was to determine the presence of pathogens in fecal samples of hospitalized patients all suffering diarrhea in addition to other problems in Mexico. Diarrheic stools from 240 patients were obtained in a third-level hospital in Monterrey, Mexico. PCR was used for the detection of Salmonella spp., Shigella spp., Campylobacter spp., Yersinia spp., Aeromonas spp., Clostridioides difficile, and norovirus GI and GII. The presence of trophozoites, cysts of protozoa, eggs, and/or helminth larvae was determined by microscopic observation. Of the 240 patients analyzed, 40.4% presented at least one of the pathogens analyzed. Norovirus was the pathogen most frequently found (28.6%), followed by bacteria (11.7%), and parasites (8.3%). The majority of co-infections were parasites + norovirus, and bacteria + norovirus. Norovirus was detected mainly in children aged 0 to 10 years (9/15, 60%). Patients aged 0-20 years did not present co-infections. Entamoeba coli and Entamoeba histolytica were the most common parasites, (8/240), and Salmonella was the most prevalent bacteria (10/240). This information can help design specific strategies useful for hospitalized people with a compromised status.
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Clinical manifestations of SARS-CoV-2 infection include more frequently fever and cough, but complications (such as pneumonia, respiratory distress syndrome, and multiorgan failure) can occur in persons with additional comorbidities. Liver dysfunction is one of the most striking affections among patients suggesting that SARS-CoV-2 may represent a new king of liver aggressor. However, the molecular process underlying this phenomenon is still unclear. In this work, we overview the most recent findings between the molecular biology of the virus, pathogenic mechanisms, and its relationship to liver disease observed in patients.
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Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Hepatopatias/virologia , Pneumonia Viral/complicações , COVID-19 , Humanos , Pandemias , SARS-CoV-2Assuntos
Pesquisa Biomédica , Gastroenterologia , Hepatite C , Antivirais/uso terapêutico , Infecções Assintomáticas , Bancos de Sangue , Transfusão de Sangue/normas , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Infecção Hospitalar/prevenção & controle , Desenvolvimento de Medicamentos , Farmacorresistência Viral , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/prevenção & controle , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Apoio à Pesquisa como Assunto , Vacinas contra Hepatite Viral/uso terapêuticoRESUMO
Some of the evidence on whether antioxidant supplements are effective in treatment of liver diseases is contradictory. Here we perform a descriptive analysis of the available data in vivo and in vitro of the possible antiviral action and controversy of several antioxidant molecules against HCV.
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Antioxidantes/uso terapêutico , Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Suplementos Nutricionais , Feminino , Humanos , Masculino , Prognóstico , Espécies Reativas de Oxigênio/metabolismo , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Gallic acid (GA) is a natural phenolic compound that possesses various biological effects, including antioxidant, anti-inflammatory, antibiotic, anticancer, antiviral and cardiovascular protection activities. In addition, numerous studies have reported that antioxidants possess antiviral activities. Hepatitis C virus (HCV) is one of the most important causes of chronic liver diseases worldwide, but until recently, only a small number of antiviral agents had been developed against HCV. Therefore, the present study investigated whether GA exhibits an anti-HCV activity. The effects of GA on HCV expression were examined using a subgenomic HCV replicon cell culture system that expressed HCV nonstructural proteins (NSs). In addition, GA cytotoxicity was evaluated at concentrations between 100-600 mg/ml using an MTT assay. Huh-7 replicon cells were incubated with 300 mg/ml GA for different times, and the HCV-RNA and protein levels were measured by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Pyrrolidine dithiocarbamate (PDTC) was used as an antioxidant control and reactive oxygen species (ROS) production was measured during the exposure. The results indicated that GA did not produce a statistically significant cytotoxicity in parental and HCV replicon cells. Furthermore, GA downregulated the expression levels of NS5A-HCV protein (~55%) and HCV-RNA (~50%) in a time-dependent manner compared with the levels in untreated cells. Notably, GA treatment decreased ROS production at the early time points of exposure in cells expressing HCV proteins. Similar results were obtained upon PDTC exposure. These findings suggest that the antioxidant capacity of GA may be involved in the downregulation of HCV replication in hepatoma cells.
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Hepatitis C virus (HCV) replication is associated with the endoplasmic reticulum, where the virus can induce cellular stress. Oxidative cell damage plays an important role in HCV physiopathology. Oxidative stress is triggered when the concentration of oxygen species in the extracellular or intracellular environment exceeds antioxidant defenses. Cells are protected and modulate oxidative stress through the interplay of intracellular antioxidant agents, mainly glutathione system (GSH) and thioredoxin; and antioxidant enzyme systems such as superoxide dismutase, catalase, GSH peroxidase, and heme oxygenase-1. Also, the use of natural and synthetic antioxidants (vitamin C and E, N-acetylcysteine, glycyrrhizin, polyenylphosphatidyl choline, mitoquinone, quercetin, S-adenosylmethionine and silymarin) has already shown promising results as co-adjuvants in HCV therapy. Despite all the available information, it is not known how different agents with antiviral activity can interfere with the modulation of the cell redox state induced by HCV and decrease viral replication. This review describes an evidence-based consensus on molecular mechanisms involved in HCV replication and their relationship with cell damage induced by oxidative stress generated by the virus itself and cell antiviral machinery. It also describes some molecules that modify the levels of oxidative stress in HCV-infected cells.