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Recent data have suggested a strong possible link between Type 2 Diabetes Mellitus and Alzheimer's disease (AD), although exact mechanisms linking the two are still a matter of research and debate. Interestingly, both are diseases with high incidence and prevalence in later years of life. The link appears so strong that some scientists use Alzheimer's and Type 3 Diabetes interchangeably. In depth study of recent data suggests that the anti diabetic drugs not only have possible role in treatment of Alzheimer's but may also arrest the declining cognitive functions associated with it. The present review gives an insight into the possible links, existing therapeutics and clinical trials of anti diabetic drugs in patients suffering from AD primarily or as co-morbidity. It may be concluded that the possible beneficial effects and usefulness of the current anti diabetic drugs in AD cannot be neglected and further research is required to achieve positive results. Currently, several drug trials are in progress to give conclusive evidence based data. [ABSTRACT FROM AUTHOR]

Natural products from plant sources, embracing inherently ample structural diversity than synthetic ones are the major sources of anticancer agents and will constantly play as protagonists for discovering new drugs. Polo-like kinases (PLKs) play a leading role in the ordered execution of mitotic events and 4 mammalian PLK family members have been identified. PLK1 is an attractive target for anticancer drugs in mammalian cells, among the four members of PLKs. The present study expresses the molecular interaction of compounds (1,2-Benzenedicarboxylic acid bis (2 ethylhexyl) ester, squalene, 3,5-bis (1,1-dimethylethyl) phenol, Pentamethyl tetrahydro-5H-chromene, (1,4-Cyclohexylphenyl) ethanone and 6-Vinyl-7-methoxy-2,2-dimethylchromene) isolated from methanolic extract of leaves of Ageratum houstonianum with PLK1 enzyme. Docking between PLK1 and each of these compounds (separately) was performed using "Auto dock 4.2." (1,4-Cyclohexylphenyl) ethanone showed the maximum potential as a promising inhibitor of PLK1 enzyme with reference to ΔG (-6.84 kcal/mol) and Ki (9.77 μM) values. This was sequentially followed by Pentamethyl tetrahydro-5H-chromene (ΔG = -6.60 kcal/mol; Ki = 14.58 μM), squalene (ΔG = -6.17 kcal/mol; Ki = 30.12 μM), 6-Vinyl-7-methoxy-2,2-dimethylchromene (ΔG = -5.91 kcal/mol; Ki = 46.68 μM), 3, 5-bis (1,1-dimethylethyl) phenol (ΔG = -5.70 kcal/mol; Ki = 66.68 μM) and 1,2-Benzenedicarboxylic acid bis (2 ethylhexyl) ester (ΔG = -5.58 kcal/mol; Ki = 80.80 μM). These results suggest that (1,4-Cyclohexylphenyl) ethanone might be a potent PLK1 inhibitor. Further, in vitro and in vivo rumination are warranted to validate the anticancer potential of (1,4-Cyclohexylphenyl) ethanone. [ABSTRACT FROM AUTHOR]

The present investigation was directed to study the possible protective activity of quercetin--a natural antioxidant against dimethoate-induced cyto- and genotoxicity in meristematic cells of Allium sativum. So far there is no report on the biological properties of quercetin in plant test systems. Chromosome breaks, multipolar anaphase, stick chromosome, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Untreated control, quercetin controls (@ 5, 10 and 20 µg/mL for 3h), and dimethoate exposed groups (@ 100 and 200 µg/mL for 3h) were maintained. For protection against cytogenotoxicity, the root tip cells treated with dimethoate at 100 and 200 µg/mL for 3h and quercetin treatment at 5, 10, and 20 µg/mL for 16 h, prior to dimethoate treatment, were undertaken. Quercetin was found to be neither cytotoxic nor genotoxic in Allium sativum control at these doses. A significant increase (P < 0.05) in chromosomal aberrations was noted in dimethoate treated Allium. Pretreatment of Allium sativum with quercetin significantly (P < 0.05) reduced dimethoate-induced genotoxicity and cytotoxicity in meristematic cells, and these effects were dose dependent. In conclusion, quercetin has a protective role in the abatement of dimethoate-induced cyto- and genotoxicity in the meristematic cells of Allium sativum that resides, at least in part, on its antioxidant effects. [ABSTRACT FROM AUTHOR]

Background: In osteosarcoma tissue, both MMP-2 and MMP-9 are over expressed compared to their expression in non-affected stromal tissue. Hence, gelatinases are attractive targets for anti-osteosarcoma drugs. Objective: To study the inhibitory activity of compounds isolated from Ageratum houstonianum against MMP-2 and MMP-9 by in-silico approach. Material and Methods: We performed docking study using 'Autodock 4.2' between 1,2-benzenedicarboxylic acid-bis (2-ethylhexyl) ester; squalene; 3,5-bis (1,1-dimethylethyl) phenol; pentamethyl tetrahydro- 5H-chromene; (1, 4-cyclohexylphenyl) ethanone and 6-vinyl-7-methoxy-2,2-dimethylchromene with MMP-2 and MMP-9. Results: Among all six compounds isolated from Ageratum houstonianum, (1, 4-cyclohexylphenyl) ethanone showed the maximum potential as a putative inhibitor of both MMP-2 and MMP-9 enzymes with reference to ΔG (-7.95 and -8.2 kcal/mol, respectively) and Ki (1.48 and 0.98 μM, respectively) values. Total intermolecular energy of docking for (1, 4-cyclohexylphenyl) ethanone-MMP catalytic domain-interaction was found to be -8.55 kcal/mol for MMP-2 and -9.21 kcal/mol for MMP-9. Conclusion: This study explores molecular interactions between human MMPs (MMP-2 and MMP-9) and six natural compounds. This study predicts that (1,4-cyclohexylphenyl) ethanone is a more effi cient inhibitor of human MMP-2 and MMP-9 enzymes compared to the other natural compounds used in this study with reference to Ki and ΔG values. [ABSTRACT FROM AUTHOR]

Plants are direct recipients of agro - toxics and therefore important materials for assessing environmental chemicals for genotoxicity. The meristematic mitotic cell of Allium cepa is an efficient cytogenetic material for chromosome aberration assay on environmental pollutants. Onion root tips were grown on moistened filter paper in petri dish at room temperature. Germinated root tips were then exposed to three concentrations of each pesticide for 24 h. About 1 - 2 mm length of root tip was cut, fixed in cornoy's fixative, hydrolyzed in warm 1 N HCL, stained with acetocarmine and squashed on glass slide. About 3000 cells were scored and classified into interphase and normal or aberrant division stage. Cytotoxicity was determined by comparing the mitotic index (MI) of treated cells with that of the negative control. The MI of cells treated with Dichlorophen and Dichlorovos at one or more concentration was half or less than that of control are said to be cytotoxic. Genotoxicity was measured by comparing the number of cells/1000 in aberrant division stages at each dose with the negative control using Mann - Whitney U test. Both Dichlorophen and Dichlorovos are genotoxic at higher concentrations i.e. 0.001%, 0.002% and 0.028%, 0.056% inducing chromosome fragment, chromosome lagging and bridges, stick chromosome and multipolar anaphase. [ABSTRACT FROM AUTHOR]

Dermatopontin (DPT) is an extensively distributed non-collagenous component of the extracellular matrix predominantly found in the dermis of the skin, and consequently expressed in several tissues. In this study, we explored the role of DPT in myogenesis and perceived that it enhances the cell adhesion, reduces the cell proliferation and promotes the myoblast differentiation in C2C12 cells. Our results reveal an inhibitory effect with fibronectin (FN) in myoblast differentiation. We also observed that DPT and fibromodulin (FMOD) regulate positively to each other and promote myogenic differentiation. We further predicted the 3D structure of DPT, which is as yet unknown, and validated it using state-of-the-art in silico tools. Furthermore, we explored the in-silico protein-protein interaction between DPT-FMOD, DPT-FN, and FMOD-FN, and perceived that the interaction between FMOD-FN is more robust than DPT-FMOD and DPT-FN. Taken together, our findings have determined the role of DPT at different stages of the myogenic process. [ABSTRACT FROM AUTHOR]

The enzyme dipeptidyl peptidase 4 (DPP4) is a potential therapeutic target for type 2 diabetes (T2DM). Many synthetic anti-DPP4 medications are available to treat T2DM. The need for secure and efficient medicines has been unmet due to the adverse side effects of existing DPP4 medications. The present study implemented a combined approach to machine learning and structure-based virtual screening to identify DPP4 inhibitors. Two ML models were trained based on DPP4 IC 50 datasets. The ML models random forest (RF) and multilayer perceptron (MLP) neural network showed good accuracy, with the area under the curve being 0.93 and 0.91, respectively. The natural compound library was screened through ML models, and 1% (217) of compounds were selected for further screening. Structure-based virtual screening was performed along with positive control sitagliptin to obtain more specific and selective leads for DPP4. Based on binding affinity, drug-likeness properties, and interaction with DPP4, Z-614 and Z-997 compounds showed high binding affinity and specificity in the catalytic pocket of DPP4. Finally, the stability conformation of the DPP4 enzyme complex was checked by a molecular dynamics (MD) simulation. The MD simulation showed that both compounds bind better in the catalytic pocket, but the Z-614 compound altered the DPP4 native conformation. Therefore, Z-614 showed a high deviation in the backbone. This combined approach (ML and structure-based) study reported that Z-997 binds most stably to DPP4 in their catalytic pocket with a binding free energy of -70.3 kJ/mol, suggesting its therapeutic potential as a treatment option for T2DM disease.Communicated by Ramaswamy H. Sarma.

Cultured meat is a potential sustainable food generated by the in vitro myogenesis of muscle satellite (stem) cells (MSCs). The self-renewal and differentiation properties of MSCs are of primary interest for cultured meat production. MSC proliferation and differentiation are influenced by a variety of growth factors such as insulin-like growth factors (IGF-1 and IGF-2), transforming growth factor beta (TGF-β), fibroblast growth factors (FGF-2 and FGF-21), platelet-derived growth factor (PDGF) and hepatocyte growth factor (HGF) and by hormones like insulin, testosterone, glucocorticoids, and thyroid hormones. In this review, we investigated the roles of growth factors and hormones during cultured meat production because these factors provide signals for MSC growth and structural stability. The aim of this article is to provide the important idea about different growth factors such as FGF (enhance the cell proliferation and differentiation), IGF-1 (increase the number of myoblasts), PDGF (myoblast proliferation), TGF-β1 (muscle repair) and hormones such as insulin (cell survival and growth), testosterone (muscle fiber size), dexamethasone (myoblast proliferation and differentiation), and thyroid hormones (amount and diameter of muscle fibers and determine the usual pattern of fiber distributions) as media components during myogenesis for cultured meat production., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2023 Korean Society of Animal Science and Technology.)

Uropathogenic strains belonging to the Enterobacteriaceae family are considered one of factors for urinary tract infections, and type 1 pilus fimbrial adhesin (FimH) and beta lactamase CTX-M-15 play crucial roles in their pathogenesis and resistance. Thus, a promising approach is to explore dual-targeting therapeutic agents that act against both FimH and CTX-M-15. In the present study, active constituents of Nigella sativa were selected on the basis of significant ‎activity against UTIs. Molecular docking was used to target active constituents of Nigella sativa to the active sites of FimH and CTX-M-15; these included thymoquinone, dithymoquinone, carvacrol, p-cymene, thymol, thymohydroquinone and longifolene. Dithymoquinone was found to be the most potent dual inhibitor, with binding energy of -7.01 and -5.38kcal/mol against CTX-M-15 and FimH, respectively; In addition, Dithymoquinone exhibited superior activity compared to positive controls avibactam and heptyl α-D-mannopyranoside. Further molecular dynamic simulation studies were carried out to assess the stability of dithymoquinone-target protein complexes via RMSD, Rg, SASA, hydrogen bond number, and RMSF analysis. Both protein-ligand complexes were conserved and attained equilibrium at around 2.0 to 2.5 ns during‎10 ns runs. These results suggest that active constituents of Nigella sativa, particularly dithymoquinone, might represent a plausible therapeutic strategy against resistant uropathogenic bacteria.

An increasing number of research evidences indicate linkage between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD); the two most common diseases of aging. In addition, T2DM and AD also share some common pathophysiological features. Therefore, dual therapy that targets both the diseases can be regarded as a beneficial approach. Acetylcholinesterase (AChE) and beta-secretase (BACE) have been considered as potential therapeutic targets for AD. Accordingly, the piece of work presented here describes the binding of anti-diabetic drugs (Jardiance, Suiny and Nesina) with AChE and BACE so as to further investigate connecting bridges concerning the treatment of these two diseases. We have used "Autodock 4.2" for docking experiments. Both, hydrogen bond and hydrophobic interactions were found to be involved in the proper positioning of these diabetic drugs within the catalytic site (CAS) of AChE and BACE enzymes to permit docking. Free energy of binding (ΔG) for 'Jardiance-AChE', 'uiny-AChE' and 'Nesina-AChE' CAS interactions were found to be -9.21, -7.32 and -10.66 kcal/mol, respectively; while for 'Jardiance-BACE', 'Suiny -BACE' and 'Nesina-BACE' CAS interactions the same were determined to be -8.91, -8.58 and -10.40 kcal/mol, respectively. Hence, these diabetic drugs might act as potent dual inhibitors for the treatment of diabetes-associated neurological disorders. Consequently, the results described herein may form the basis of future dual therapy against the same.

Enzyme-inhibition is considered as a potent therapeutic approach to the treatment of diseases associated with acetylcholinesterase (AChE). The present study elucidates molecular interactions of human brain AChE, with three natural ligands Lycodine, Cernuine and Fawcettimine for comparison. Docking between these ligands and enzyme was performed using 'Autodock 4.2'. It was determined that polar and hydrophobic interactions play an important role in the correct positioning of Lycodine, Cernuine and Fawcettimine within the 'catalytic site' of AChE to permit docking. This approach would be helpful to understand the selectivity of the given drug molecule in the treatment of neurological disorder. Moreover, the present study confirms that Lycodine is a more efficient inhibitor of human brain AChE compared to Cernuine and Fawcettimine with reference to ΔG and Ki values.

This review presents a concise update on the inhibitors of the neuroenzyme, acetylcholinesterase (AChE; EC 3.1.1.7). AChE is a serine protease, which hydrolyses the neurotransmitter, acetylcholine into acetate and choline thereby terminating neurotransmission. Molecular interactions (mode of binding to the target enzyme), clinical applications and limitations have been summarized for each of the inhibitors discussed. Traditional inhibitors (e.g. physostigmine, tacrine, donepezil, rivastigmine etc.) as well as novel inhibitors like various physostigmine-derivatives have been covered. This is followed by a short glimpse on inhibitors derived from nature (e.g. Huperzine A and B, Galangin). Also, a discussion on 'hybrid of pre-existing drugs' has been incorporated. Furthermore, current status of therapeutic applications of AChEinhibitors has also been summarized.

Natural products from plant sources, embracing inherently ample structural diversity than synthetic ones are the major sources of anticancer agents and will constantly play as protagonists for discovering new drugs. Polo-like kinases (PLKs) play a leading role in the ordered execution of mitotic events and 4 mammalian PLK family members have been identified. PLK1 is an attractive target for anticancer drugs in mammalian cells, among the four members of PLKs. The present study expresses the molecular interaction of compounds (1,2-Benzenedicarboxylic acid bis (2 ethylhexyl) ester, squalene, 3,5-bis (1,1-dimethylethyl) phenol, Pentamethyl tetrahydro-5H-chromene, (1,4-Cyclohexylphenyl) ethanone and 6-Vinyl-7-methoxy-2,2-dimethylchromene) isolated from methanolic extract of leaves of Ageratum houstonianum with PLK1 enzyme. Docking between PLK1 and each of these compounds (separately) was performed using "Auto dock 4.2." (1,4-Cyclohexylphenyl) ethanone showed the maximum potential as a promising inhibitor of PLK1 enzyme with reference to ∆G (-6.84 kcal/mol) and Ki (9.77 μM) values. This was sequentially followed by Pentamethyl tetrahydro-5H-chromene (∆G = -6.60 kcal/mol; Ki = 14.58 μM), squalene (∆G = -6.17 kcal/mol; Ki = 30.12 μM), 6-Vinyl-7-methoxy-2,2-dimethylchromene (∆G = -5.91 kcal/mol; Ki = 46.68 μM), 3, 5-bis (1,1-dimethylethyl) phenol (∆G = -5.70 kcal/mol; Ki = 66.68 μM) and 1,2-Benzenedicarboxylic acid bis (2 ethylhexyl) ester (∆G = -5.58 kcal/mol; Ki = 80.80 μM). These results suggest that (1,4-Cyclohexylphenyl) ethanone might be a potent PLK1 inhibitor. Further, in vitro and in vivo rumination are warranted to validate the anticancer potential of (1,4-Cyclohexylphenyl) ethanone.