A Synopsis of Hepatitis C Virus Treatments and Future Perspectives.

Hepatitis C virus (HCV) infection is a worldwide public health problem. Chronic infection with HCV can lead to liver cirrhosis or cancer. Although some immune-competent individuals can clear the virus, others develop chronic HCV disease due to viral mutations or an impaired immune response. IFNs type I and III and the signal transduction induced by them are essential for a proper antiviral effect. Research on the viral cycle and immune escape mechanisms has formed the basis of therapeutic strategies to achieve a sustained virological response (SVR). The first therapies were based on IFNα; then, IFNα plus ribavirin (IFN-RBV); and then, pegylated-IFNα-RBV (PEGIFNα-RIV) to improve cytokine pharmacokinetics. However, the maximum SVR was 60%, and several significant side effects were observed, decreasing patients' treatment adherence. The development of direct-acting antivirals (DAAs) significantly enhanced the SVR (>90%), and the compounds were able to inhibit HCV replication without significant side effects, even in paediatric populations. The management of coinfected HBV-HCV and HCV-HIV patients has also improved based on DAA and PEG-IFNα-RBV (HBV-HCV). CD4 cells are crucial for an effective antiviral response. The IFNλ3, IL28B, TNF-α, IL-10, TLR-3, and TLR-9 gene polymorphisms are involved in viral clearance, therapeutic responses, and hepatic pathologies. Future research should focus on searching for strategies to circumvent resistance-associated substitution (RAS) to DAAs, develop new therapeutic schemes for different medical conditions, including organ transplant, and develop vaccines for long-lasting cellular and humoral responses with cross-protection against different HCV genotypes. The goal is to minimise the probability of HCV infection, HCV chronicity and hepatic carcinoma.

SARS-CoV-2 Infection in Venezuelan Pediatric Patients-A Single Center Prospective Observational Study.

Several studies suggest that children infected with SARS-CoV-2 have fewer clinical manifestations than adults; when they develop symptoms, they rarely progress to severe disease. Different immunological theories have been proposed to explain this phenomenon. In September 2020, 16% of the active COVID-19 cases in Venezuela were children under 19 years. We conducted a cross-sectional study of pediatric patients' immune response and clinical conditions with SARS-CoV-2 infection. The patients were admitted to the COVID-19 area of the emergency department of Dr José Manuel de los Ríos Children's Hospital (2021-2022). The lymphocyte subpopulations were analyzed by flow cytometry, and IFNγ, IL-6, and IL-10 serum concentrations were quantified using commercial ELISA assays. The analysis was conducted on 72 patients aged one month to 18 years. The majority, 52.8%, had mild disease, and 30.6% of the patients were diagnosed with MIS-C. The main symptoms reported were fever, cough, and diarrhea. A correlation was found between IL-10 and IL-6 concentrations and age group, lymphocyte subpopulations and nutritional status and steroid use, and IL-6 concentrations and clinical severity. The results suggest a different immune response depending on age and nutritional status that should be considered for treating pediatric COVID-19 patients.

Synthesis and antimalarial and anticancer evaluation of 7-chlorquinoline-4-thiazoleacetic derivatives containing aryl hydrazide moieties.

Twelve 7-chloroquinoline derivatives were designed and synthesized using the principle of molecular hybridization through the coupling of 2-[2-(7-chloroquinolin-4-ylthio)-4-methylthiazol-5-yl]acetic acid 1 with various benzoyl hydrazines 2a-l. The synthetic compounds were tested as antimalarials. Some of them showed an efficient in vitro activity as inhibitors of ß-hematin formation and an in vivo activity in a murine model, resulting in compounds 8 and 9 as the most active ones with IC50 values of 0.65 ± 0.09 and 0.64 ± 0.16 µM, respectively. The effects of the compounds on the cell viability, cell cycle, and apoptosis induction of A549 and MCF-7 cancer cell lines were also examined. Our data showed that compounds 6 and 12 were the most active agents, decreasing the cell viability of MCF-7 cells with IC50 values of 15.41 and 12.99 µM, respectively. None of the compounds analyzed significantly affected the viability of peripheral blood mononuclear cells. Also, significant induction of apoptosis was observed when both cancer cell lines were incubated with compounds 6 and 12. In MCF-7 cells, treatment with these compounds led to cell cycle arrest in the G0/G1 phase. The results obtained suggest that these structures may be useful in developing new therapies for malaria and cancer treatment.

Producción de anticuerpos IgA contra componentes proteicos del huevo de Ascaris lumbricoides en el suero de niños infectados / Production of IgA antobodies against protein components of eggs from Ascaris lumbricoides in serum of infected children

La ascariasis es una enfermedad causada por el nematodo A. lumbricoides afectando a 1 billón de personas en todo el mundo. En este trabajo se analiza la respuesta de anticuerpos IgA específicos frente a extractos de huevos de A. lumbricoides en el suero de niños de comunidades rurales del estado Miranda. Se evaluaron 100 niños entre 3 y 14 años de edad y se tomaron muestras de suero y el diagnóstico coproparasitológico. Según lo reportado fueron clasificados en: infectados solo por A. lumbricoides (Asc+), no infectados (NSOP), infectados con A. lumbricoides y otros parásitos (Asc+/OP+) e individuos no infectados por A. lumbricoides pero con otros parásitos intestinales (Asc-/OP+). El extracto fue probado por ELISA, Western Blot e inmunocitoquímica. El perfil electroforético del extracto mostró 7 bandas proteicas de 102, 92, 85, 65, 50, 45 y 30kDa. Por la ELISA, el 26% de los pacientes infectados por A. lumbricoides fueron seropositivos, mientras que el 56% en el grupo NSOP fueron seronegativos. El ensayo de inhibición con extracto de A. lumbricoides permitió identificar 3 bandas proteicas especificas reconocidas por la inmunoglobulina IgA de 92, 85 y 65 kDa diferentes a las reconocidas por el extracto de verme adulto. El nivel de anticuerpos fue significativamente mayor en los infectados que en los no infectados. La superficie de los huevos fue reconocida por la IgA en el suero de los individuos infectados. Estos resultados, indican que el huevo de Ascaris induce anticuerpos específicos contra proteínas que podrían ser utilizados como antígenos en pruebas serológicas que complementan el diagnóstico de Ascariasis.

Ascariasis is a disease caused by the nematode A. lumbricoides affecting 1 billion people worldwide. In this study the specific response for IgA antibodies against extracts of A. lumbricoides eggs in the serum of children in rural areas of Miranda state. One hundred children were evaluated at ages 3 and 14 and were taken serum samples and diagnosis of stools. According to the reported, were classified into four groups: infected by A. lumbricoides (Asc +), uninfected (NSOP), infected A. lumbricoides and other parasite (Asc +/OP +); and individuals with other parasitic infections without A. lumbricoides (ASC/ OP+). The extract was tested by ELISA, Western blotting and immunocytochemestry. The electrophoretic profile showed 7 bands of 102, 92, 85, 65, 50, 45 and 30kDa. By ELISA, the 26% of patients in group A. lumbricoides were positive, while the 56% in the NSOP group were seronegative. Immune assay by inhibition with A. lumbricoides extract allowed identify three bands for the IgA antibodies of 92, 85 and 65 kDa different to the bands recognized by adult extracts of A. lumbricoiedes. The levels of antibodies were significantly higher in infected than non-infected children. In addition, the protein component on the surface of eggs was recognized by sera of infected individuals. These results indicate that eggs of Ascaris induce specific antibodies against proteins that could be used as antigens in serological diagnosis for complementing the diagnosis for Ascariasis.