Synthesis of potent vasodilating agents: in silico and in vitro evaluation of 6-(4-substitutedphenyl)-3-pyridazinone derivatives as potential hydralazine analogues.

People of all age categories and lifestyles suffer to different extents from hypertension. Accordingly, this necessitates the rise of new ways to defeat this enemy. Vasodilators exert a principal portion of highly effectual antihypertensive agents; our research is focused on the design, synthesis and biological evaluation of a new series of 6-(4-substitutedphenyl)-3-pyridazinones as potential hydralazine vasodilator analogues implementing both in vitro and in silico approaches.

miRNAs: possible regulators of toll like receptors and inflammatory tumor microenvironment in colorectal cancer.

Background: Colorectal cancer (CRC) is ranked as the third most commonly diagnosed cancer and the third cause of cancer related deaths. CRC is greatly attributed to genetic and epigenetic mutations and immune dysregulation. Tumor aberrant expression of Toll-like Receptors (TLRs) can contribute to tumorigenesis.

The impact of education level on Knowledge, Attitudes and Practices towards COVID-19 in Edo State, Nigeria.

Background: For effective Public Health measures, factors that influence Knowledge, Attitudes and Practices (KAP) need to be understood. In this paper, we document the relationship between levels of education on the KAP towards COVID-19 among the population of Edo State, Nigeria.

Methods: A cross-sectional KAP questionnaire was delivered across 13 communities.

Ameliorative effect of betanin on experimental cisplatin-induced liver injury; the novel impact of miRNA-34a on the SIRT1/PGC-1α signaling pathway.

The anticancer agent, cisplatin (CIS), is associated with hepatotoxic effects related to activation of oxidative stress and inflammation pathways. CIS-induced oxidative DNA damage reduces sirtuin 1 (SIRT1) activity, which in turn, modulates the activity of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α). Moreover, microRNA-34a (miRNA-34a) was shown to hinder both SIRT1 and nuclear factor erythroid 2-related factor 2 (Nrf2) activity.

A Cyclodextrin-Stabilized Spermine-Tagged Drug Triplex that Targets Theophylline to the Lungs Selectively in Respiratory Emergency.

Ion-pairing a lifesaving drug such as theophylline with a targeting moiety could have a significant impact on medical emergencies such as status asthmaticus or COVID-19 induced pneumomediastinum. However, to achieve rapid drug targeting in vivo the ion-pair must be protected against breakdown before the entry into the target tissue. This study aims to investigate if inserting theophylline, when ion-paired to the polyamine transporter substrate spermine, into a cyclodextrin (CD), to form a triplex, could direct the bronchodilator to the lungs selectively after intravenous administration.

Implications of miRNAs on TGF-β/TAK1/mTOR pathway in mediating the renoprotective effects of pentoxifylline against cisplatin-induced nephrotoxicity in rats.

Cisplatin (CIS)-mediated nephrotoxicity is induced via transforming growth factor-beta (TGF-β) and TGF-β-activated kinase (TAK1). TGF-β and TAK1 are known to interact with microRNA-let-7b and microRNA-26b, respectively. Additionally, TGF-β1 is reported to down-regulate the autophagy marker microtubule-associated protein 1 light chain 3-II (LC3-II) through upregulation of microRNA-34a.

Crocin attenuates cisplatin-induced hepatotoxicity via TLR4/NF-κBp50 signaling and BAMBI modulation of TGF-β activity: Involvement of miRNA-9 and miRNA-29.

TLR4-induced mitigation of the BMP down-regulation and activin membrane bound inhibitor (BAMBI) and the consequent enhancement of the transforming growth factor-beta (TGF-β) profibrogenic signaling has not yet been studied in cisplatin (CIS)-induced hepatotoxicity. miRNA-9 and29 have been previously reported to modulate TLR4 signaling via either tempering the expression of nuclear factor kappa-B p50 (NF-κB p50) or downregulation of extracellular matrix genes respectively. Hence we aimed to investigate the involvement of TLR4-induced modulation of TGF-β receptor 1 (TGF-βR1) signaling as well as the implication of miRNA-9 and 29 in CIS-induced hepatotoxicity.

Region-specific blood-brain barrier transporter changes leads to increased sensitivity to amisulpride in Alzheimer's disease.

Background: Research into amisulpride use in Alzheimer's disease (AD) implicates blood-brain barrier (BBB) dysfunction in antipsychotic sensitivity. Research into BBB transporters has been mainly directed towards the ABC superfamily, however, solute carrier (SLC) function in AD has not been widely studied. This study tests the hypothesis that transporters for organic cations contribute to the BBB delivery of the antipsychotics (amisulpride and haloperidol) and is disrupted in AD.

COX-2 Docking Structural Analysis with Phytochemical Extracts of Rosemary: A Possible Cytotoxicity on Head and Neck Squamous Cell Carcinoma Cell Line (HEp-2).

Background: Various phenolic phytochemical extracts have been claimed to exhibit different types of biological activity, including anti-inflammatory, anti-oxidative and anti-carcinogenic activity. Carnosol and carnosic acid, extracts of rosemary, are among these phenolic compounds.

Materials And Methods: CHARMm-based molecular docking was performed to estimate the possible molecular interactions of both carnosic acid and carnosol with the COX-2 active binding site.

Targeting subcellular localization through the polo-box domain: non-ATP competitive inhibitors recapitulate a PLK1 phenotype.

The polo-box domain (PBD) has critical roles in the mitotic functions of polo-like kinase 1 (PLK1). The replacement with partial ligand alternative through computational enrichment (REPLACE) strategy to develop inhibitors of protein-protein interactions has identified alternatives for the N-terminal tripeptide of a Cdc25C substrate. In addition, a peptide structure-activity relationship described key determinants and novel information useful for drug design.