No abstract

Angiotensin Converting Enzyme (ACE) regulates blood pressure. ACE converts angiotensin I to angiotensin II which binds with its receptors and through a cascade of reactions constrict blood vesels, consequently results in increased blood pressure, called hypertension. Inhibition of ACE activity is considered as an useful therapeutic target that reduce hypertension. Moringa oleifera leaves have traditionally been used in Ayurvedic medicine for their antihypertensive activity and antihypertensive effect of Moringa leaves was reported on spontaneously hypertensive rats. So, we hypothesize that Moringa oleifera leaves methanolic extract (MOLME) might inhibit ACE activity. Inhibition of ACE activity by MOLME was estimated in vitro. In this study, inhibition of ACE by MOLME was evaluated by spectrophotometric method. MOLME inhibited ACE activity in the substrate hippuryl-Lhistidyl-L-leucine (HHL) with an IC50 value of 226.37 μg/ml with a reference compound, captropril (CP), a potent ACE inhibitor with an IC50 value of 0.0289 μM. The mode of ACE inhibition in HHL with or without MOLME revealed that the Vmax (0.0857 and 0.0541 OD/30 min, respectively) was changed and the Km values were 4.671 and 4.41. The results indicate that MOLME acts as a non-competitive inhibitor for ACE. CP was found a competitive inhibitor of ACE. MOLME might be a potential natural inhibitor of ACE which reduces hypertension.

aims: The goal of this study was to identify potential drug target proteins and agents for the treatment of HCC. background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death globally. The mechanisms underlying the development of HCC have remained mostly unknown till now. objective: i) The first goal was to identify key genomic biomarkers related to HCC, highlighting their functions, pathways, and regulatory factors; (ii) the second goal was to investigate candidate drugs for HCC treatments; and (iii) the final goal was to propose potential candidate drugs against HCC based on identified biomarkers. method: The publicly available three mRNA expression profiles from the GEO database were utilized to analyze the differentially expressed genes (DEGs) in HCC. The identification of Hub-DEGs, regulator’s analysis, and survival of HCC patients were conducted by integrated bioinformatics methods. Finally, the top-ranked drug targets and agents were identified by molecular docking study for HCC. result: We identified 160 common differentially expressed genes (cDEGs) and, through protein-protein interaction, ten genes (CDKN3, TK1, NCAPG, CDCA5, RACGAP1, AURKA, PRC1, UBE2T, MELK, and ASPM) were selected as Hub-DEGs. The GO functional and KEGG pathway enrichment analyses of Hub-DEGs revealed several important functions and signaling pathways that are significantly related to HCC. The interaction network analysis identified three TF proteins and eight miRNAs as the key transcriptional and post-transcriptional regulators of Hub-DEGs. Considering Hub-DEGs, 3 key TFs proteins and already published 7 top-ranked meta-genes as drug target receptors, and performed their docking analysis with a list of 172 meta-agent drugs for HCC. We observed that lead five drugs were common with our proposed and published receptors based on their binding affinities. conclusion: Dactinomycin, Vincristine, Sirolimus, Valrubicin, and Navitoclax showed strong binding affinities with proposed receptors, suggesting that the selected drugs may play a vital role in the treatment of HCC. other: The present study emphasizes further wet lab experimental validation for both the proposed target proteins and candidate drugs.

No abstract

Naturally occurring ribozymes with a modular architecture are promising platforms for construction of RNA nanostructures because modular redesign enables their oligomerization. The resulting RNA nanostructures can exhibit the catalytic function of the parent ribozyme in an assembly dependent manner. In this study, we designed and constructed open-form oligomers of a bimolecular form of an RNase P ribozyme. The ribozyme oligomers were analyzed biochemically and by atomic force microscopy (AFM).