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These positive changes were significantly inhibited by microinjecting EX527 into the VLO. These results suggest that SIRT1 in the VLO may mediate morphine-induced behavioral sensitization and the overexpression of SIRT1, p-ERK and BDNF could be the potential mechanism. Taken together, the results of our research provide evidence to support that SIRT1 play an important role in morphine vulnerability and microinjecting EX527 into the VLO could significantly suppress morphine addiction in rats.Deoxynivalenol (DON) poses a serious health threat to animals and humans consuming DON-contaminated food and feed. Biological means of detoxification of DON are considered as one of the effective strategies. The aim of the work was to study ameliorative effects of Bacillus subtilis ASAG 216 on DON-induced toxicosis in piglets. A decrease in average daily gain and average daily feed intake was observed in piglets fed DON-contaminated feed. In addition, DON exposure increased the serum concentrations of aspartate aminotransferase, immunoglobulin A, diamine oxidase, endotoxin, and peptide YY. Moreover, DON exposure caused oxidative stress in the serum, liver and jejunum, induced intestinal inflammation, impaired the intestinal barrier, and disturbed the gut microbiota homeostasis. Supplementation of B. subtilis ASAG 216 effectively attenuated the aforementioned effects of DON on piglets. Moreover, DON and de-epoxy-DON (DOM-1) in the serum, liver and kidney were significantly decreased when B. subtilis ASAG 216 was added to DON-contaminated diet. Our results imply that B. subtilis ASAG 216 can protect against DON-induced toxicosis in piglets, and thus this strain has a potential to be used as an animal feed ingredient to counteract harmful effects of DON in animals.
COVID-19, the presently prevailing global public health emergency has culminated in international instability in economy. LY2780301 Akt inhibitor This unprecedented pandemic outbreak pressingly necessitated the trans-disciplinary approach in developing novel/new anti-COVID-19 drugs especially, small molecule inhibitors targeting the seminal proteins of viral etiological agent, SARS-CoV-2.
Based on the traditional medicinal knowledge, we made an attempt through molecular docking analysis to explore the phytochemical constituents of three most commonly used Indian herbs in 'steam inhalation therapy' against well recognized viral receptor proteins.
A total of 57 phytochemicals were scrutinized virtually against four structural protein targets of SARS-CoV-2 viz. 3CL
, ACE-2, spike glycoprotein and RdRp. Providentially, two bioactives from each of the three plants i.e. apigenin-o-7-glucuronide and ellagic acid from Eucalyptus globulus; eudesmol and viridiflorene from Vitex negundo and; vasicolinone and anisotine from Justicia adhatoda were identified to be the best hit lead molecules based on interaction energies, conventional hydrogen bonding numbers and other non-covalent interactions. On comparison with the known SARS-CoV-2 protease inhibitor -lopinavir and RdRp inhibitor -remdesivir, apigenin-o-7-glucuronide was found to be a phenomenal inhibitor of both protease and polymerase, as it strongly interacts with their active sites and exhibited remarkably high binding affinity. Furthermore, in silico drug-likeness and ADMET prediction analyses clearly evidenced the usability of the identified bioactives to develop as drug against COVID-19.
Overall, the data of the present study exemplifies that the phytochemicals from selected traditional herbs having significance in steam inhalation therapy would be promising in combating COVID-19.
Overall, the data of the present study exemplifies that the phytochemicals from selected traditional herbs having significance in steam inhalation therapy would be promising in combating COVID-19.Previous reports reveal that +9/-9 polymorphism of the bradykinin B2 receptor (BDKRB2) is suggestive of cardiometabolic diseases. The aim of this study was to examine the impact of BDKRB2 + 9/-9 polymorphism genotypes on the blood pressure parameters and microvascular function in prepubescent children. We screened for BDKRB2 + 9/-9 polymorphism in the DNA of 145 children (86 boys and 59 girls), and its association with body composition, blood pressure levels, biochemical parameters, and endothelial function was determined. No significant association of the BDKRB2 genotypes with gender (P=0.377), race (P=0.949) or family history of cardiovascular disease (CVD) (P=0.858) was observed. Moreover, we did not identify any interaction between BDKRB2 genotypes with a phenotype of obesity (P=0.144). Children carrying the +9/+9 genotype exhibited a significant linear trend with higher levels of systolic blood pressure and pulse pressure (P less then 0.001). Moreover, the presence of +9 allele resulted in a decrease of reactive hyperemia index, showing a decreasing linear trend from -9/-9 to +9/+9, wherein this parameter of endothelial function was the lowest in the +9/+9 children, intermediate in the +9/-9 children, and the highest in the -9/-9 children (P less then 0.001). There was a significant inverse correlation between reactive hyperemia index and systolic blood pressure (r= - 0.348, P less then 0.001) and pulse pressure (r= - 0.399, P less then 0.001). Our findings indicate that the +9/+9 BDKRB2 genotype was associated with high blood pressure and microvascular dysfunction in prepubescent Brazilian children.Cells secrete extracellular vesicles (EVs) for intercellular communication. EVs are natural nanovesicles that are surrounded by lipid bilayer for delivery of assorted cargoes for therapeutic purposes. In addition to their therapeutic roles, these vesicles are potential drug delivery systems. Exosomes are the most studied EVs as the delivery carriers that can cross the blood-brain barrier (BBB) because of their nanosize. BBB is a diffusion barrier that is selective for small molecules to transit from blood to the brain. This barrier has been an obstacle for the delivery of drugs to the brain for the treatment of neurological disorders (NDs). For efficient drug delivery, synthetic vesicles such as liposomes have been employed as carriers for delivery of therapeutic molecules in clinical practice. However, these delivery systems are not without drawbacks. Among the limitations of these drug carriers include recognition by the body as foreign particles that encounter multiple defence systems that could recognize, neutralize and eliminate them.
