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The G protein-coupled receptor 40 (GPR40) is known to exert a significant influence on neurogenesis and neurodevelopment within the central nervous system of both humans and rodents. Research findings indicate that the activation of GPR40 by an agonist has been observed to promote the proliferation and viability of hypothalamus cells in the human body. The objective of the present study is to discover new agonist compounds for the GPR40 protein through the utilization of machine learning and pharmacophore-based screening techniques, in conjunction with other computational methodologies such as docking, molecular dynamics simulations, free energy calculations, and investigations of the free energy landscape. In the course of our investigation, we successfully identified five unreported agonist compounds that exhibit robust docking score, displayed stability in ligand RMSD and consistent hydrogen bonding with the receptor in the MD trajectories. Free energy calculations were observed to be higher than control molecule. The measured binding affinities of compounds namely 1, 3, 4, 6 and 10 were -13.9, -13.5, -13.4, -12.9, and -12.1 Kcal/mol, respectively. The identified molecular agonist that has been found can be assessed in terms of its therapeutic efficacy in the treatment of neurological diseases. [ABSTRACT FROM AUTHOR]

Medicinal plants have a long history of treating diseases in animals and humans in Ethiopia. Nevertheless, not enough research has been done on the antibacterial properties and possible bioactive components of the majority of medicinal plants. Therefore, this study was concerned with the evaluation of the percentage yield, phytochemical, antimicrobial, antifungal, MIC, antiradical activities, phenolic content, and X‐ray fluorescence spectroscopy (XRF) analysis of A. otallensis plant extracts. The mean values of antimicrobial, antifungal, MIC, antiradical, phenolic content, and XRF analysis were reported as mean ± standard deviation. The solvent methanol showed a higher degree of yield in leaf and root extract which was 8.45 (22.27%) and 3.12 g (15.58%), respectively, while distilled water extract of leaf and root showed less degree of yield which was 0.22 g (1.10%) and 0.42 g (2.1%), respectively. Qualitative phytochemical analyses of the plant parts have revealed the presence of various components of metabolites like alkaloids, flavonoids, phenol, saponins, tannins, steroids, steroids, terpenoids, triterpenoids, glycosides, anthraquinones, diterpenes, phytosterols, and phlobatannals. A. otallensis gel extracts had shown significant antibacterial and antifungal activity against the test bacterial and fungus, respectively. Moreover, the methanolic gel extracts of A. otallensis demonstrated notable antiradical activity than the leaf and the root. The highest value of phenolic content was obtained in A. otallensis; gel, leaf, and root extract which was 61.9 ± 0.5 mg/g, 53.6 ± 0.3 mg/g, and 51.6 ± 0.6 mg/g, respectively. In this study, twelve elements in the plant parts of A. otallensis were determined using XRF spectroscopy. Overall, this research contributes to the understanding of the pharmacological potential of A. otallensis and highlights the importance of further research into its medicinal properties. The results provide valuable insights into the use of medicinal plants to treat diseases and support the development of natural therapeutics. [ABSTRACT FROM AUTHOR]

Protein kinase C (PKC) is a diverse enzyme family crucial for cell signalling in various organs. Its dysregulation is linked to numerous diseases, including cancer, cardiovascular disorders, and neurological problems. In the brain, PKC plays pivotal roles in synaptic plasticity, learning, memory, and neuronal survival. Specifically, PKC's involvement in Alzheimer's Disease (AD) pathogenesis is of significant interest. The dysregulation of PKC signalling has been linked to neurological disorders, including AD. This review elucidates PKC's pivotal role in neurological health, particularly its implications in AD pathogenesis and chronic alcohol addiction. AD, characterised by neurodegeneration, implicates PKC dysregulation in synaptic dysfunction and cognitive decline. Conversely, chronic alcohol consumption elicits neural adaptations intertwined with PKC signalling, exacerbating addictive behaviours. By unravelling PKC's involvement in these afflictions, potential therapeutic avenues emerge, offering promise for ameliorating their debilitating effects. This review navigates the complex interplay between PKC, AD pathology, and alcohol addiction, illuminating pathways for future neurotherapeutic interventions. [ABSTRACT FROM AUTHOR]

Chemical-induced neurotoxicity is increasingly recognized to accelerate the development of neurodegenerative disorders (NDs), which pose an increasing health burden to society. Attempts are being made to develop drugs that can cross the blood-brain barrier and have minimal or no side effects. Nobiletin (NOB), a polymethoxylated flavonoid with anti-oxidative and antiinflammatory effects, has been demonstrated to be a promising compound to treat a variety of NDs. Here, we investigated the potential role of NOB in sodium arsenate (NA)-induced deregulated miRNAs and target proteins in human neural progenitor cells (hNPCs). The proteomics and microRNA (miRNA) profiling was done for different groups, namely, unexposed control, NA-exposed, NA + NOB, and NOB groups. Following the correlation analysis between deregulated miRNAs and target proteins, RTPCR analysis was used to validate the selected genes. The proteomic analysis showed that significantly deregulated proteins were associated with neurodegeneration pathways, response to oxidative stress, RNA processing, DNA repair, and apoptotic process following exposure to NA. The OpenArray analysis confirmed that NA exposure significantly alteredmiRNAs that regulate P53 signaling, Wnt signaling, cell death, and cell cycle pathways. The RT-PCR validation studies concur with proteomic data as marker genes associated with autophagy and apoptosis (HO-1, SQSTM1, LC-3, Cas3, Apaf1, HSP70, and SNCA1) were altered following NA exposure. It was observed that the treatment of NOB significantly restored the deregulated miRNAs and proteins to their basal levels. Hence, it may be considered one of its neuroprotective mechanisms. Together, the findings are promising to demonstrate the potential applicability of NOB as a neuroprotectant against chemical-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Aerobic metabolism in plants results in the production of hydrogen peroxide (H2O2), a significant and comparatively stable non-radical reactive oxygen species (ROS). H2O2 is a signaling molecule that regulates particular physiological and biological processes (the cell cycle, photosynthesis, plant growth and development, and plant responses to environmental challenges) at low concentrations. Plants may experience oxidative stress and ultimately die from cell death if excess H2O2 builds up. Triticum dicoccoides, Triticum urartu, and Triticum spelta are different ancient wheat species that present different interesting characteristics, and their importance is becoming more and more clear. In fact, due to their interesting nutritive health, flavor, and nutritional values, as well as their resistance to different parasites, the cultivation of these species is increasingly important. Thus, it is important to understand the mechanisms of plant tolerance to different biotic and abiotic stresses by studying different stress-induced gene families such as catalases (CAT), which are important H2O2-metabolizing enzymes found in plants. Here, we identified seven CAT-encoding genes (TdCATs) in Triticum dicoccoides, four genes in Triticum urartu (TuCATs), and eight genes in Triticum spelta (TsCATs). The accuracy of the newly identified wheat CAT gene members in different wheat genomes is confirmed by the gene structures, phylogenetic relationships, protein domains, and subcellular location analyses discussed in this article. In fact, our analysis showed that the identified genes harbor the following two conserved domains: a catalase domain (pfam00199) and a catalase-related domain (pfam06628). Phylogenetic analyses showed that the identified wheat CAT proteins were present in an analogous form in durum wheat and bread wheat. Moreover, the identified CAT proteins were located essentially in the peroxisome, as revealed by in silico analyses. Interestingly, analyses of CAT promoters in those species revealed the presence of different cis elements related to plant development, maturation, and plant responses to different environmental stresses. According to RT-qPCR, Triticum CAT genes showed distinctive expression designs in the studied organs and in response to different treatments (salt, heat, cold, mannitol, and ABA). This study completed a thorough analysis of the CAT genes in Triticeae, which advances our knowledge of CAT genes and establishes a framework for further functional analyses of the wheat gene family. [ABSTRACT FROM AUTHOR]