Human Norovirus belongs to a family Calciviridae, and was identified in the outbreak of gastroenteritis in Norwalk, due to its seasonal prevalence known as "winter vomiting disease." Treatment of Norovirus infection is still mysterious because there is no effective antiviral drugs or vaccine developed to protect against the infection, to eradicate the infection an effective vaccine should be developed. In this study, capsid protein (A7YK10), small protein (A7YK11), and polyprotein (A7YK09) were utilized. These proteins were subjected to B and T cell epitopes prediction by using reliable immunoinformatics tools. https://www.selleckchem.com/products/srt2104-gsk2245840.html The antigenic and non-allergenic epitopes were selected for the subunit vaccine, which can activate cellular and humoral immune responses. Linkers joined these epitopes together. The vaccine structure was modelled and validated by using Errat, ProSA, and rampage servers. The modelled vaccine was docked with TLR-7. The stability of the docked complex was evaluated by MD simulation. To apply the concept in a wet lab, the reverse translated vaccine sequence was cloned in pET28a (+). The vaccine developed in this study requires experimental validation to ensure its effectiveness against the disease. Communicated by Ramaswamy H. Sarma.Background Adiponectin is known to mediate antidiabetic and cardioprotective metabolic effects. Current evidence suggests that diet, both its quantity and quality, affects adiponectin concentration. Methods The purpose of this study was to evaluate the association of adiponectin with cardiometabolic risk factors, anthropometric features, and diet characteristics in obese patients with multiple cardiometabolic risk factors. The group of 113 nondiabetic patients (90 males, mean age 48 ± 9 years) fulfilling the criteria of metabolic syndrome (IDF, 2005) was divided into 2 subgroups according to median adiponectin concentration calculated for that cohort (6.83 μg/mL)-low-adiponectin (LA) and high-adiponectin (HA) subgroup. Biochemical and anthropometric measurements were recorded and nutrients intake was assessed using 24-hr dietary recall method and diet history questionnaire. Results No significant differences between LA and HA were noted regarding the anthropometric parameters. However, there were significant differences in biochemical indices, and HA was characterized by a more favorable insulin level, homeostasis model assessment of insulin resistance (HOMA-IR) value, and plasma lipid profile than LA. Both LA and HA subgroups were comparable in terms of energy, protein, carbohydrate, and total fat intake, but there were significant differences between the level of polyunsaturated fatty acids (PUFA) consumption (6.06 ± 1.0 and 6.37 ± 1.1, respectively) and omega-3/omega-6 ratio (as follows 0.09 ± 0.01 and 0.16 ± 0.04). Conclusions These results highlight interactions between diet, adiponectin concentration, and biochemical profile. Nondiabetic patients with metabolic syndrome with higher PUFA consumption, including higher omega-3/omega-6 ratio, were characterized by higher circulating adiponectin level and more favorable biochemical profile. Thus, it might be assumed that the protective role of omega-3 fatty acids might be mediated by adiponectin in patients with metabolic syndrome.Alzheimer's disease (AD) is one of the most familiar multifactorial and complex neurodegenerative disorders characterized by loss of cholinergic neurons in the brain. The various attempts for drug development to treat AD have been hampered by largely unsuccessful clinical trials in the last two decades. Developing a new drug from scratch takes enormous amounts of time, effort and money, mainly due to several barriers in the therapeutic drug development process. Drug repurposing strategy resuscitates this slow drug discovery process by finding new uses and clinical indications for existing drugs. This study is focused on the cholinergic hypothesis, a well-established target of the clinically available drugs in the market for the treatment of AD. The computational virtual screening (VS) led to the identification of thiazolidinedione (TZD, antidiabetic) and aminoquinoline (antimalarial) class of drugs as acetylcholinesterase (AChE) inhibitors. Intriguingly, rosiglitazone (RGZ) and hydroxychloroquine (HCQ) were found to be mild-to-moderate inhibitors of hAChE (human acetylcholinesterase) in our enzyme inhibition studies which are complementary to our computational studies. On the basis of our computational and experimental studies, it can be suggested that the beneficial effect of RGZ and HCQ in AD patients reported in the literature may partly be due to their AChE inhibitory property. The VS also led to the identification of antifungal drugs miconazole and oxiconazole as potential AChE inhibitors. The molecular dynamics (MD) simulation of the potential hits belonging to TZD, aminoquinoline and azoles class were also carried out. The MD simulations studies revealed detailed computational insights related to molecular interactions and protein-ligand stability for selected hits. Communicated by Ramaswamy H. Sarma.Microsporidia are a group of unicellular and opportunistic intestinal parasites in which Enterocytozoon bieneusi is a frequent species causing microsporidial infections in humans. Many domesticated and wild animals have been shown to be hosts of E. bieneusi and other microsporidia. The role of hedgehogs in the ecology of microsporidia is unclear; therefore, we investigated the prevalence and genetic diversity of E. bieneusi, Cryptosporidium, and Blastocystis spp. in hedgehogs (Erinaceus amurensis) collected from Hubei Province in Central China. PCR amplification of the internal transcribed spacer region of the ribosomal DNA indicated that 9.8% (4/41) hedgehogs were positive to E. bieneusi, but none (0/41) was positive to Cryptosporidium and Blastocystis spp. Phylogenetic analysis showed the strains detected from the hedgehogs belong to four novel genotypes (EA1-EA4), which were most closely related to type IV of group 1c. This study demonstrated that hedgehogs are hosts of E. bieneusi and may play a role in the transmission of E.
Human Norovirus belongs to a family Calciviridae, and was identified in the outbreak of gastroenteritis in Norwalk, due to its seasonal prevalence known as "winter vomiting disease." Treatment of Norovirus infection is still mysterious because there is no effective antiviral drugs or vaccine developed to protect against the infection, to eradicate the infection an effective vaccine should be developed. In this study, capsid protein (A7YK10), small protein (A7YK11), and polyprotein (A7YK09) were utilized. These proteins were subjected to B and T cell epitopes prediction by using reliable immunoinformatics tools. https://www.selleckchem.com/products/srt2104-gsk2245840.html The antigenic and non-allergenic epitopes were selected for the subunit vaccine, which can activate cellular and humoral immune responses. Linkers joined these epitopes together. The vaccine structure was modelled and validated by using Errat, ProSA, and rampage servers. The modelled vaccine was docked with TLR-7. The stability of the docked complex was evaluated by MD simulation. To apply the concept in a wet lab, the reverse translated vaccine sequence was cloned in pET28a (+). The vaccine developed in this study requires experimental validation to ensure its effectiveness against the disease. Communicated by Ramaswamy H. Sarma.Background Adiponectin is known to mediate antidiabetic and cardioprotective metabolic effects. Current evidence suggests that diet, both its quantity and quality, affects adiponectin concentration. Methods The purpose of this study was to evaluate the association of adiponectin with cardiometabolic risk factors, anthropometric features, and diet characteristics in obese patients with multiple cardiometabolic risk factors. The group of 113 nondiabetic patients (90 males, mean age 48 ± 9 years) fulfilling the criteria of metabolic syndrome (IDF, 2005) was divided into 2 subgroups according to median adiponectin concentration calculated for that cohort (6.83 μg/mL)-low-adiponectin (LA) and high-adiponectin (HA) subgroup. Biochemical and anthropometric measurements were recorded and nutrients intake was assessed using 24-hr dietary recall method and diet history questionnaire. Results No significant differences between LA and HA were noted regarding the anthropometric parameters. However, there were significant differences in biochemical indices, and HA was characterized by a more favorable insulin level, homeostasis model assessment of insulin resistance (HOMA-IR) value, and plasma lipid profile than LA. Both LA and HA subgroups were comparable in terms of energy, protein, carbohydrate, and total fat intake, but there were significant differences between the level of polyunsaturated fatty acids (PUFA) consumption (6.06 ± 1.0 and 6.37 ± 1.1, respectively) and omega-3/omega-6 ratio (as follows 0.09 ± 0.01 and 0.16 ± 0.04). Conclusions These results highlight interactions between diet, adiponectin concentration, and biochemical profile. Nondiabetic patients with metabolic syndrome with higher PUFA consumption, including higher omega-3/omega-6 ratio, were characterized by higher circulating adiponectin level and more favorable biochemical profile. Thus, it might be assumed that the protective role of omega-3 fatty acids might be mediated by adiponectin in patients with metabolic syndrome.Alzheimer's disease (AD) is one of the most familiar multifactorial and complex neurodegenerative disorders characterized by loss of cholinergic neurons in the brain. The various attempts for drug development to treat AD have been hampered by largely unsuccessful clinical trials in the last two decades. Developing a new drug from scratch takes enormous amounts of time, effort and money, mainly due to several barriers in the therapeutic drug development process. Drug repurposing strategy resuscitates this slow drug discovery process by finding new uses and clinical indications for existing drugs. This study is focused on the cholinergic hypothesis, a well-established target of the clinically available drugs in the market for the treatment of AD. The computational virtual screening (VS) led to the identification of thiazolidinedione (TZD, antidiabetic) and aminoquinoline (antimalarial) class of drugs as acetylcholinesterase (AChE) inhibitors. Intriguingly, rosiglitazone (RGZ) and hydroxychloroquine (HCQ) were found to be mild-to-moderate inhibitors of hAChE (human acetylcholinesterase) in our enzyme inhibition studies which are complementary to our computational studies. On the basis of our computational and experimental studies, it can be suggested that the beneficial effect of RGZ and HCQ in AD patients reported in the literature may partly be due to their AChE inhibitory property. The VS also led to the identification of antifungal drugs miconazole and oxiconazole as potential AChE inhibitors. The molecular dynamics (MD) simulation of the potential hits belonging to TZD, aminoquinoline and azoles class were also carried out. The MD simulations studies revealed detailed computational insights related to molecular interactions and protein-ligand stability for selected hits. Communicated by Ramaswamy H. Sarma.Microsporidia are a group of unicellular and opportunistic intestinal parasites in which Enterocytozoon bieneusi is a frequent species causing microsporidial infections in humans. Many domesticated and wild animals have been shown to be hosts of E. bieneusi and other microsporidia. The role of hedgehogs in the ecology of microsporidia is unclear; therefore, we investigated the prevalence and genetic diversity of E. bieneusi, Cryptosporidium, and Blastocystis spp. in hedgehogs (Erinaceus amurensis) collected from Hubei Province in Central China. PCR amplification of the internal transcribed spacer region of the ribosomal DNA indicated that 9.8% (4/41) hedgehogs were positive to E. bieneusi, but none (0/41) was positive to Cryptosporidium and Blastocystis spp. Phylogenetic analysis showed the strains detected from the hedgehogs belong to four novel genotypes (EA1-EA4), which were most closely related to type IV of group 1c. This study demonstrated that hedgehogs are hosts of E. bieneusi and may play a role in the transmission of E.
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