Reciprocal crosslink among MeCP2/BDNF /CREB signaling pinpointed in autism spectrum disorder.

Autism spectrum disorder, or individual disability (ID), is a condition characterized by complications in social interaction, restricted repetitive behavior, and difficulties in social communication. Neuquinon (NQ) possess a powerful therapeutic potential in various neurodegenerative disease. Nevertheless, contributing to NQ's low water solubility and bioavailability, its medicinal use has been constrained. Liposomes were supposed to be prospective drug-delivering agents for NQ, crossing the blood-brain barrier (BBB), and reaching the target organs. The current investigation aims to track the signaling pathways that govern NQ and liposomal neuquinon (LNQ) action in autistic models generated by ethyl formic acid. The neurotransmitters gamma amino-butyric acid (GABA), acetylcholine (ACh), and acetylcholinesterase (AChE) in addition to, the gene expressions of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and methyl-CpG-binding protein 2 (MeCP2) and the DNA damage COMET analysis at different time intervals of the study, were assessed. EFA in a dose of 500 mg/kg BW was used to induce autism in rats, and then NQ and LNQ were administered in 10 mg/kg and 2 mg/kg BW, respectively. The results revealed that NQ and LNQ significantly down-regulated BDNF, GABA, and AChE; on the other hand, they up-regulated MeCP2, CREB gene expressions, and ACh action. NQ and LNQ displayed improvement in DNA damage in almost all brain regions after EFA alterations; even better results were noticed post-LNQ therapy. Therefore, it may be concluded that neuquinon and liposomal-loaded neuquinon have a therapeutic index versus EFA-induced autism in a rat model.

Development of a New Benzofuran-Pyrazole-Pyridine-Based Molecule for the Management of Osteoarthritis.

Osteoarthritis is a substantial burden for patients with the disease. The known medications for the disease target the mitigation of the disease's symptoms. So, drug development for the management of osteoarthritis represents an important challenge in the medical field. This work is based on the development of a new benzofuran-pyrazole-pyridine-based compound 8 with potential anti-inflammatory and anti-osteoarthritis properties. Microanalytical and spectral data confirmed the chemical structure of compound 8. The biological assays indicated that compound 8 produces multifunctional activity as an anti-osteoarthritic candidate via inhibition of pro-inflammatory mediators, including RANTES, CRP, COMP, CK, and LPO in OA rats. Histopathological and pharmacokinetic studies confirmed the safety profile of the latter molecule. Accordingly, compound 8 is considered a promising anti-osteoarthritis agent and deserves deeper investigation in future trials.

Calcium voltage-gated channel subunit alpha 1 C and glial fibrillary acidic protein signaling pathways as a selective biomarker in predicting the efficacy of liposomal loaded co-enzyme Q in the autistic rat model.

Autism spectrum disorder (ASD) is an extreme neuropsychotic disturbance with both environmental and genetic origins. Sodium propionate (PPA) a metabolic bioproduct of gut microbiota is well-thought-out as a successful autism animal model. Nevertheless, Liposomal drug delivery system possess the advantagous of biocompatibility, targeting organs, ability to carry large drug payloads and skipping macrophages for this purpose the current study was carried out to investigate the hypothesis that Calcium Voltage-Gated channel subunit alpha 1 C (CACNA1C) and glial fibrillary acidic protein (GFAP) signaling pathways crosstalk with the efficacy of Co-enzyme Q10 (Co-Q10) and liposomal loaded Co-enzyme Q10 (L Co-Q10) in PPA mediated autistic rat model. Autism was conducted by buffered PPA (500 mg/Kg b.wt) daily for 5 consecutive days subsequently treatment via Co-Q10 in a dose of (10 mg/kg b.wt) and L Co-Q10 (2 mg/kg b.wt) for four weeks then the autistic model was followed for signs of autism at different time intervals of (one, two and four weeks). The control, PPA intoxicated, and treated groups were subjected to behavioral tests (Y-Maze and open field), antioxidant analysis, gene expression analysis, and histological examination at different time intervals of the study. The results revealed that Co-Q10 and L Co-Q10 significantly elevated antioxidative stress biomarkers, comprising superoxide dismutase (SOD), glutathione (GSH), and total antioxidant capacity (TAC). In addition, they significantly ameliorated the oxidative stress biomarker malondialdehyde (MDA). Meanwhile, they significantly downregulated GFAP and CACNA1C mRNA gene expressions, Co-Q10 and LCo-Q10 showed improvement in almost brain regions post PPA histopathological alterations, even better results were manifested via LCo-Q10 groups. These results showed the superiority of LCo-Q10 over Co-Q10 in competing autism. In conclusion: The administration of anti-inflammatory and antioxidant agents such as Co-Q10 and L Co-Q10 may represent a promising strategy to counteract pathological behaviors in ASD model via targeting organs, increasing retention time, and reducing side effects.

Synthesis and Evaluation of New Coumarin Derivatives as Antioxidant, Antimicrobial, and Anti-Inflammatory Agents.

New pyranocoumarin and coumarin-sulfonamide derivatives were prepared and evaluated for their antioxidant, antimicrobial, and/or anti-inflammatory activities. Coumarin-sulfonamide compounds 8a-d demonstrated significant antioxidant activity, while 7c,d, 8c,d, and 9c,d exhibited antimicrobial activity equal to or higher than the standard antimicrobials against at least one tested microorganism. Regarding the anti-inflammatory testing, pyranocoumarins 2b, 3a,b and 5c and coumarin-sulfonamide compound 9a showed more potent antiproteinase activity than aspirin in vitro; however, five compounds were as potent as aspirin. The anti-inflammatory activity of the promising compounds was further assessed pharmacologically on formaldehyde-induced rat paw oedema and showed significant inhibition of oedema. For in vitro COX-inhibitory activity of coumarin derivatives, pyranocoumarin derivative 5a was the most selective (SI = 152) and coumarin-sulfonamide derivative 8d was most active toward COX-2 isozyme. The most active derivatives met the in silico criteria for orally active drugs; thus, they may serve as promising candidates to develop more potent and highly efficient antioxidant, antimicrobial, and/or anti-inflammatory agents.

A Comparative Study of the Anticancer Activity and PARP-1 Inhibiting Effect of Benzofuran-Pyrazole Scaffold and Its Nano-Sized Particles in Human Breast Cancer Cells.

Breast cancer is considered the most common and deadly cancer among women worldwide. Nanomedicine has become extremely attractive in the field of cancer treatment. Due to the high surface to volume ratio and other unique properties, nanomaterials can be specifically targeted to certain cells and tissues to interact with the living systems. The strategic planning of this study is based on using the nanoprecipitation method to prepare nanoparticles BZP-NPs (3.8-5.7 nm) of the previously prepared benzofuran-pyrazole compound (IV) BZP which showed promising cytotoxic activity. The capacity of BZP and BZP-NPs to suppress the growth of human breast tumor MCF-7 and MDA-MB-231 cells was evaluated using MTT assay. The IC50 doses of BZP and BZP-NPs targeting normal breast cells MCF-12A exceeded those targeting the cancer cells by >1000-fold, demonstrating their reasonable safety profiles in normal cells. Furthermore, cell cycle analysis, apoptosis induction detection, assessment of p53, Bcl-2, caspase-3, and PARP-1 levels of BZP and its nano-sized-BZP-NPs particles were also evaluated. Although the obtained results were in the favor of compound IV in its normal-sized particles, BZP-NPs appeared as a hit compound which showed improved cytotoxicity against the tested human breast cancer cells associated with the induction of pre-G1 apoptosis as well as cell cycle arrest at G2/M phase. The increase in caspase-3 level, upregulation of p53, and downregulation of Bcl-2 protein expression levels confirmed apoptosis. Furthermore, ELISA results exhibited that BZP-NPs produced a more favorable impact as a PARP-1 enzyme inhibitor than the parent BZP.

Phytochemical and in vitro screening of some Ficus and Morus spp. for hypolipidaemic and antioxidant activities and in vivo assessment of Ficus mysorensis (Roth).

Phytochemical screening of air-dried leaves and fruit juice of certain Ficus and Morus spp. have been studied. In an in vitro study, the ethanol and hexane extracts of the investigated plants were evaluated against hyperlipidaemia by estimating the rate limiting enzyme of cholesterol biothenysis; ß-hydroxy-ß-methylglutaryl coenzyme A reductase (HMG-CoA reductase). The antioxidant activity was evaluated by reduction of DPPH(-) free radical. Extra phytochemical screening of Ficus extracts was undertaken, which recorded potent hypolipidaemic and antioxidant activities. The more pronounced extract, Ficus mysorensis (hexane extract), was evaluated in vivo by estimation of the lipid profile and certain antioxidant parameters in hypercholesterolemic rats. The hexane fraction was chromatographed and six isolated compounds were identified. Furthermore, its saponifiable fraction was identified by a MS/MS technique. In conclusion, F. mysorensis recorded hypolipidaemic and antioxidant effects. Detailed studies of the isolated compounds must be undertaken for an evaluation against hypercholesterolemia and free radical elevation.

Effect of Allium cepa and Allium sativum feeding on glucose, glycogen, protein bands profile and phenol oxidase activity in Biomphalaria alexandrina.

Feeding B. alexandrina on onion and garlic powder (Allium cepa and Allium sativum) separately exert some biological and biochemical changes. The effect of the two plants on glucose and glycogen which are the energy fuel of the snails, and on phenol oxidase (PO) activity after 1, 2, 3 and 7 days were studied. Different protein bands were separated from the control and treated snails haemolymph after 24 hours and one week by using SDS-electrophoresis. The study revealed that glucose and glycogen were decreased significantly after feeding on onion and garlic. Also phenol oxidase (PO) activity was highly significantly decreased after 2 and 7 days of feeding on garlic while feeding on onion decreased the activity of the enzyme at all periods. Data obtained from SDS-electrophoresis showed variations in the different protein bands reflect the enzymatic change in the snails' tissue. So, the snails' fecundity may be reduced and in turn disturb the life cycle of schistosome parasite.