RESUMO
Heme oxygenase-1 (HO-1) is considered to be the main protein in diseases arising as a result of oxidative and inflammatory insults. Tremendous research has been carried out on HO-1 since years, pertaining its cytoprotective effect against oxidative injury and other cellular stresses. HO-1, by regulating intracellular levels of pro-oxidant heme, or by other benefits of its by-products such as carbon monoxide (CO) and biliverdin (BV) had become an important candidate protein to be up-regulated to combat diverse stressful events. Although the beneficial effects of HO-1 induction have been reported in a number of cells and tissues, a growing body of evidence indicates that this increased HO-1 expression may lead to the progression of several diseases such as neurodegeneration, carcinogenesis. But it is not clear, what accounts for the increased expression of HO-1 in cells and tissues. The observed friendly role of HO-1 in a wide range of stress conditions since times is now doubtful. Therefore, more studies are needed to elucidate the exact role of HO-1 in various stressful events. Being more concise, elucidating the effect of HO-1 up-regulation on critical genes involved in particular diseases such as cancer will help to a larger extent to comprehend the exact role of HO-1. This review will assist in understanding the dual role (protective and detrimental) of HO-1 and the signaling pathway involved and will help in unraveling the doubtful role of HO-1 induction.
Assuntos
Heme Oxigenase-1/biossíntese , Animais , Indução Enzimática , Heme/metabolismo , Heme Oxigenase-1/metabolismo , Humanos , Transdução de SinaisRESUMO
White matter disease refers to a set of diseases that affect the white matter of the brain and all of which have different consequences on brain function. Most of the studies have shown that it results from the defects during protein synthesis, with the gene defects in EIF2B 1-5, encoding the five subunits of eukaryotic translation initiation factor 2B (eIF2B) α, ß, γ, δ and ε, respectively. eIF2B plays a crucial role in protein translation and its regulation under different conditions. The previous studies have shown that mutations in five subunits of eIF2B cause white matter disease of the brain and thus EIF2B is the main culprit in development of white matter disease. In this study, the mutational screening of EIF2B5 gene encoding eIF2Bε was performed for the first time in 12 Kashmiri patients, each having a unique white matter disease condition. We found two novel missense mutations in EIF2B5: c.580A>G, p.Thr194Ala and c.611C>T, p.Ala204Val among the patients with demyelinating disease (multiple sclerosis), but no mutation was found in other patients. In conclusion our study suggests involvement of the EIF2B5 gene in MS development, thus suggesting p.Thr194Ala to be a susceptibility factor for the development of multiple sclerosis.
Assuntos
Fator de Iniciação 2B em Eucariotos/genética , Éxons/genética , Predisposição Genética para Doença , Esclerose Múltipla/genética , Mutação de Sentido Incorreto/genética , Estudos de Casos e Controles , DNA/sangue , DNA/genética , Fator de Iniciação 2B em Eucariotos/química , Humanos , Índia , Esclerose Múltipla/sangue , Conformação ProteicaRESUMO
The coronavirus disease (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created havoc worldwide. Due to the non-availability of any vaccine or drugs against COVID-19, immunotherapies involving convalescent plasma, immunoglobulins, antibodies (monoclonal or polyclonal), and the use of immunomodulatory agents to enhance immunity are valuable alternative options. Cell-based therapies including natural killer cells, T cells, stem cells along with cytokines and toll-like receptors (TLRs) based therapies are also being exploited potentially against COVID-19. Future research need to strengthen the field of developing effective immunotherapeutics and immunomodulators with a thrust of providing appropriate, affordable, convenient, and cost-effective prophylactic and treatment regimens to combat global COVID-19 crisis that has led to a state of medical emergency enforcing entire countries of the world to devote their research infrastructure and manpower in tackling this pandemic.
Assuntos
COVID-19 , Infecções por Coronavirus , COVID-19/terapia , Humanos , Imunização Passiva , Imunoterapia , SARS-CoV-2 , Soroterapia para COVID-19RESUMO
The COVID-19 pandemic caused by SARS-CoV-2 has spread rapidly. To date, countries have relied on the prevention of the disease through isolation, quarantine, and clinical care of affected individuals. However, studies on the roles of asymptomatic and mildly infected subjects in disease transmission, use of antiviral drugs, and vaccination of the general population will be very important for mitigating the effects of the eventual return of this pandemic. Initial investigations are ongoing to evaluate antigenic structures of SARS-CoV-2 and the immunogenicity of vaccine candidates. There also is a need to comprehensively compile the details of previous studies on SARS-related vaccines that can be extrapolated to identify potent vaccine targets for developing COVID-19 vaccines. This review aims to analyze previous studies, current status, and future possibilities for producing SARS-CoV-2 vaccines.
Assuntos
Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , SARS-CoV-2/efeitos dos fármacos , COVID-19/imunologia , COVID-19/metabolismo , COVID-19/terapia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/metabolismo , Humanos , Imunização Passiva , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Soroterapia para COVID-19RESUMO
Achieving nutritional requirements for pregnant women in rural or suburban households while maintaining the intake of local and culture-specific foods can be difficult. Usage of a linear programming approach can effectively generate diet optimization models that incorporate local and culturally acceptable menus. This study aimed to determine whether a realistic and affordable diet that achieves recommended nutrient intakes for pregnant women could be formulated from locally available foods in Malaysia. A cross-sectional study was conducted to assess the dietary intake of 78 pregnant women using a 24-h dietary recall and a 3-day food record. A market survey was also carried out to estimate the cost of raw foods that are frequently consumed. All linear programming analyses were done using Excel Solver to generate optimal dietary patterns. Our findings showed that the menus designed from diet optimization models using locally available foods would improve dietary adequacy for the seven food groups based on the Malaysian Dietary Guidelines 2010 (MDG 2010) and the 14 nutrients based on Recommended Nutrient Intake 2017 (RNI 2017) in pregnant women. However, inadequacies remained for iron and niacin, indicating that these nutrients may require supplementation.
Assuntos
Dieta Saudável/estatística & dados numéricos , Ingestão de Energia/fisiologia , Gestantes , Adulto , Estudos Transversais , Comportamento Alimentar/etnologia , Feminino , Humanos , Malásia/epidemiologia , Fenômenos Fisiológicos da Nutrição Materna , Necessidades Nutricionais , Gravidez , Programação Linear , Recomendações NutricionaisRESUMO
Relaxin, a peptide hormone has emerged as a cardioprotective agent against the heart failure and has been found to protect cardiac muscle cells against hypoxia/reoxygenation injury under in vitro conditions. The present study was conducted to study its possible role in activating the Nrf2/HO-1 signaling pathway in cardiomyocytes, as a means to counter hypoxia associated oxidative damage and cell death. H9C2 cell line was induced with chemical hypoxia alone or together with relaxin. Hypoxia associated cellular damage and reactive oxygen species (ROS) production was accessed by Lactate dehydrogenase (LDH) release and DCFDA activity respectively. The anti-oxidative property of RLXH2 was measures by assessing the activities of different enzymes like Superoxide dismutase (SOD), Catalase (CAT) and Glutathione peroxidase (GSX). Expression levels of Nrf2 and HO-1 was studied by immunoblotting and quantitative real time PCR (qRT-PCR). Translocation of Nrf2 to nucleus was studied by immunoblotting. Our results found that hypoxia associated lactate dehydrogenase leakage and ROS production is countered by RLXH2 treatment. Similarly, RLXH2 was able to counter hypoxia induced oxidative damage as evident by increased activities of SOD, CAT and GSX. Furthermore, it was found that RLXH2 treatment induces translocation of Nrf2 from cytosol to nucleus and in turn enhances expression level of HO-1. Our results suggest that RLXH2 exerts cytoprotective action in cardiomyocytes against the hypoxia induced damage and activates Nrf2/HO-1 signaling pathway.
Assuntos
Miócitos Cardíacos/efeitos dos fármacos , Relaxina/farmacologia , Relaxina/fisiologia , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Cardiotônicos/metabolismo , Cardiotônicos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/fisiologia , Humanos , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Inflammation constitutes one of the important components of colorectal cancer (CRC) pathogenesis. Tumor necrosis factor-α (TNF-α), a cytokine and an important inflammatory mediator plays a pivotal role in the malignant cellular proliferation, angiogenesis, tissue invasion and metastasis in CRC. The studies on association of various polymorphisms in human TNF-α gene including TNF-α-308G/A single nucleotide polymorphism (SNP) are limited, mixed and inconclusive. MATERIALS AND METHODS: The aim of this study was to analyze the association of TNF-α-308G/A promoter SNP with colorectal cancer (CRC) susceptibility and development risk and also to evaluate the modifying effects of possible TNF-α-308G/A genotypes on different risk factors of CRC in ethnic population of Kashmir, India through a case-control setup. The genotype frequencies of TNF-α-308G/A promoter SNP were compared between 142 CRC patients and 184 individually matched healthy controls by using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. The associations between the TNF-α-308G/A SNP and CRC risk were examined through conditional logistic regression models adjusted for multiple possible confounding (third) variables. Further, the associations between this SNP and various clinico-pathological parameters, demographic variables and environmental factors within the case group subjects with regard to CRC risk were also evaluated. RESULTS: The association between the TNF-α-308G/A SNP and the modulation of risk of CRC was not found to be significant (p value = 0.156). The effect of less common TNF-α-308A allele on the risk of colorectal cancer was also not found to be significant (p value = 0.175). The variant genotype (AA) was nonexistent in the study population. Further, we found no significant effect modulation of CRC risk by wild and heterozygous TNF-α-308G/A SNP genotypes in presence of different possible risk factors (p > 0.05). We also found no significant association of TNF-α-308G/A SNP with the subsets of various characteristics of the case group subjects under study (p > 0.05). CONCLUSIONS: This study indicates that there is no significant association between the TNF-α-308G/A promoter SNP and the risk of developing CRC in ethnic Kashmiri population. However, in order to substantiate our findings, this study needs to be replicated with bigger sample size and should involve other ethnically defined populations with high CRC risk.