Antimicrobial Activity of Citrate-Coated Cerium Oxide Nanoparticles.

The purpose of this study was to investigate the antimicrobial activity of citrate-stabilized sols of cerium oxide nanoparticles at different concentrations via different microbiological methods and to compare the effect with the peroxidase activity of nanoceria for the subsequent development of a regeneration-stimulating medical and/or veterinary wound-healing product providing new types of antimicrobial action. The object of this study was cerium oxide nanoparticles synthesized from aqueous solutions of cerium (III) nitrate hexahydrate and citric acid (the size of the nanoparticles was 3-5 nm, and their aggregates were 60-130 nm). Nanoceria oxide sols with a wide range of concentrations (10-1-10-6 M) as well as powder (the dry substance) were used. Both bacterial and fungal strains (Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Proteus vulgaris, Candida albicans, Aspergillus brasielensis) were used for the microbiological studies. The antimicrobial activity of nanoceria was investigated across a wide range of concentrations using three methods sequentially; the antimicrobial activity was studied by examining diffusion into agar, the serial dilution method was used to detect the minimum inhibitory and bactericidal concentrations, and, finally, gas chromatography with mass-selective detection was performed to study the inhibition of E. coli's growth. To study the redox activity of different concentrations of nanocerium, we studied the intensity of chemiluminescence in the oxidation reaction of luminol in the presence of hydrogen peroxide. As a result of this study's use of the agar diffusion and serial dilution methods followed by sowing, no significant evidence of antimicrobial activity was found. At the same time, in the current study of antimicrobial activity against E. coli strains using gas chromatography with mass spectrometry, the ability of nanoceria to significantly inhibit the growth and reproduction of microorganisms after 24 h and, in particular, after 48 h of incubation at a wide range of concentrations, 10-2-10-5 M (48-95% reduction in the number of microbes with a significant dose-dependent effect) was determined as the optimum concentration. A reliable redox activity of nanoceria coated with citrate was established, increasing in proportion to the concentration, confirming the oxidative mechanism of the action of nanoceria. Thus, nanoceria have a dose-dependent bacteriostatic effect, which is most pronounced at concentrations of 10-2-10-3 M. Unlike the effects of classical antiseptics, the effect was manifested from 2 days and increased during the observation. To study the antimicrobial activity of nanomaterials, it is advisable not to use classical qualitative and semi-quantitative methods; rather, the employment of more accurate quantitative methods is advised, in particular, gas chromatography-mass spectrometry, during several days of incubation.

Secondary metabolites of Trichoderma spp. as EGFR tyrosine kinase inhibitors: Evaluation of anticancer efficacy through computational approach.

The present study explores the epidermal growth factor receptor (EGFR) tyrosine kinase inhibition efficacy of secondary metabolites in Trichoderma spp. through molecular docking, molecular dynamics (MD) simulation and MM-PBSA approach. The result of molecular docking confirmed that out of 200 metabolites screened, three metabolites such as Harzianelactone A, Pretrichodermamide G and Aspochalasin M, potentially bound with the active binding site of EGFR tyrosine kinase domain(PDB ID: 1M17) with a threshold docking score of ≤- 9.0 kcal/mol when compared with the standard EGFR inhibitor (Erlotinib). The MD simulation was run to investigate the potential for stable complex formation in EGFR tyrosine kinase domain-unbound/lead metabolite (Aspochalasin M)-bound/standard inhibitor (Erlotinib)-bound complex. The MD simulation analysis at 100 ns revealed that Aspochalasin M formed the stable complex with EGFR. Besides, the in silico predication of pharmacokinetic properties further confirmed that Aspochalasin M qualified the drug-likeness rules with no harmful side effects (viz., hERG toxicity, hepatotoxicity and skin sensitization), non-mutagenicity and favourable logBB value. Moreover, the BOILED-Egg model predicted that Aspochalasin M showed a higher gastrointestinal absorption with improved bioavailability when administered orally and removed from the central nervous system (CNS). The results of the computational studies concluded that Aspochalasin M possessed significant efficacy in binding EGFR's active sites compared to the known standard inhibitor (Erlotinib). Therefore, Aspochalasin M can be used as a possible anticancer drug candidate and further in vitro and in vivo experimental validation of Aspochalasin M of Trichoderma spp. are required to determine its anticancer potential.

Simultaneous determination of cystine and other free aminothiols in blood plasma using capillary electrophoresis with pH-mediated stacking.

We developed a method of sensitive capillary electrophoresis using UV detection for the determination of certain free aminothiols (reduced cysteinylglycine (rCysGly), cysteine (rCys), glutathione (rGln), and cystine (CysS) in human blood plasma. The reduced thiols were derivatized with N-ethylmaleimide. The plasma was purified from proteins via ultrafiltration. Electrophoretic separation was performed using 115 mM Na phosphate with 7.5% (v/v) polyethylene glycol 600, pH 2.3. The in-capillary concentration of the analytes was achieved with a pH gradient created via the preinjection of triethanolamine and postinjection of phosphoric acid. The separation was carried out using a silica capillary (50 µm i.d.; total/effective separation length 42/35 cm) at a 25 kV voltage. The total analysis/regeneration time was 18 min. The quantification limits varied from 1.3 µM (rCysGly) to 5.4 µM (CysS). The accuracy was 95%-99%, and the repeatability and reproducibility were approximately 1.8%-3.8% and 1.9%-5.0%, respectively. An analysis of plasma samples from healthy volunteers (N = 41) showed that the mean levels of rCysGly, rCys, rGln, and CysS were 1.64, 10.6, 2.58, and 46.2 µM, respectively.

Influence of the Synthesis Scheme of Nanocrystalline Cerium Oxide and Its Concentration on the Biological Activity of Cells Providing Wound Regeneration.

In the ongoing search for practical uses of rare-earth metal nanoparticles, cerium dioxide nanoparticles (nanoceria) have received special attention. The purpose of this research was to study the biomedical effects of nanocrystalline forms of cerium oxide obtained by different synthesis schemes and to evaluate the effect of different concentrations of nanoceria (from 10-2 to 10-6 M) on cells involved in the regeneration of skin cell structures such as fibroblasts, mesenchymal stem cells, and keratinocytes. Two different methods of nanoceria preparation were investigated: (1) CeO-NPs-1 by precipitation from aqueous solutions of cerium (III) nitrate hexahydrate and citric acid and (2) CeO-NPs-2 by hydrolysis of ammonium hexanitratocerate (IV) under conditions of thermal autoclaving. According to the X-ray diffraction, transmission electron microscopy, and dynamic light scattering data, CeO2-1 consists of individual particles of cerium dioxide (3-5 nm) and their aggregates with diameters of 60-130 nm. CeO2-2 comprises small aggregates of 8-20 nm in diameter, which consist of particles of 2-3 nm in size. Cell cultures of human fibroblasts, human mesenchymal stem cells, and human keratinocytes were cocultured with different concentrations of nanoceria sols (10-2, 10-3, 10-4, 10-5, and 10-6 mol/L). The metabolic activity of all cell types was investigated by MTT test after 48 and 72 h, whereas proliferative activity and cytotoxicity were determined by quantitative cell culture counting and live/dead test. A dependence of biological effects on the method of nanoceria preparation and concentration was revealed. Data were obtained with respect to the optimal concentration of sol to achieve the highest metabolic effect in the used cell cultures. Hypotheses about the mechanisms of the obtained effects and the structure of a fundamentally new medical device for accelerated healing of skin wounds were formulated. The method of nanoceria synthesis and concentration fundamentally and significantly change the biological activity of cell cultures of different types-from suppression to pronounced stimulation. The best biological activity of cell cultures was determined through cocultivation with sols of citrate nanoceria (CeO-NPs-1) at a concentration of 10-3-10-4 M.

Zinc oxide nanoparticles prepared through microbial mediated synthesis for therapeutic applications: a possible alternative for plants.

Zinc oxide nanoparticles (ZnO-NPs) synthesized through biogenic methods have gained significant attention due to their unique properties and potential applications in various biological fields. Unlike chemical and physical approaches that may lead to environmental pollution, biogenic synthesis offers a greener alternative, minimizing hazardous environmental impacts. During biogenic synthesis, metabolites present in the biotic sources (like plants and microbes) serve as bio-reductants and bio-stabilizers. Among the biotic sources, microbes have emerged as a promising option for ZnO-NPs synthesis due to their numerous advantages, such as being environmentally friendly, non-toxic, biodegradable, and biocompatible. Various microbes like bacteria, actinomycetes, fungi, and yeast can be employed to synthesize ZnO-NPs. The synthesis can occur either intracellularly, within the microbial cells, or extracellularly, using proteins, enzymes, and other biomolecules secreted by the microbes. The main key advantage of biogenic synthesis is manipulating the reaction conditions to optimize the preferred shape and size of the ZnO-NPs. This control over the synthesis process allows tailoring the NPs for specific applications in various fields, including medicine, agriculture, environmental remediation, and more. Some potential applications include drug delivery systems, antibacterial agents, bioimaging, biosensors, and nano-fertilizers for improved crop growth. While the green synthesis of ZnO-NPs through microbes offers numerous benefits, it is essential to assess their toxicological effects, a critical aspect that requires thorough investigation to ensure their safe use in various applications. Overall, the presented review highlights the mechanism of biogenic synthesis of ZnO-NPs using microbes and their exploration of potential applications while emphasizing the importance of studying their toxicological effects to ensure a viable and environmentally friendly green strategy.

The Diagnostic and Prognostic Roles Played by Homocysteine and Other Aminothiols in Patients with Chronic Kidney Disease.

We examined standard clinical and laboratory biochemical parameters, as well as the levels of aminothiols in the blood and urine (homocysteine (Hcy), cysteine (Cys), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH)) via capillary electrophoresis in patients with CKD at stages II-V. Patient outcomes were assessed after five years. To complete forecasting, correlation and ROC analysis were performed. It was found that the levels of Cys and Hcy in blood plasma were earlier markers of CKD starting from stage II, while the levels of SAM and SAM/SAH in urine made it possible to differentiate between CKD at stages II and III. Blood plasma Hcy and urinary SAM and SAM/SAH correlated with mortality, but plasma Hcy concentrations were more significant. Thus, plasma Hcy, urine SAM, and SAM/SAH can be considered to be potential diagnostic and prognostic markers in patients with CKD.

Cell cycle arrest and apoptotic studies of Terminalia chebula against MCF-7 breast cancer cell line: an in vitro and in silico approach.

Breast cancer is a leading cause of mortality in women, and alternative therapies with fewer side effects are actively being explored. Breast cancer is a significant global health concern, and conventional treatments like radiotherapy and chemotherapy often have side effects. Medicinal plant extracts offer a promising avenue for the development of effective and safe anticancer therapies. Terminalia chebula, a plant known for its medicinal properties, was selected for investigation in this study. We aimed to assess the antiproliferative effects of TCF extract on breast cancer cells and explore the potential role of saccharopine, a phytochemical found in TCF, as an anticancer agent. MCF7 breast cancer cell lines were exposed to TCF extract, and cell viability and apoptosis assays were performed to evaluate the antiproliferative and apoptogenic effects. Molecular docking studies were conducted to assess the binding affinity of saccharopine with EGFRs. Molecular dynamics simulations and binding energy calculations were employed to analyze the stability of the EGFR-saccharopine complex. The TCF extract exhibited significant antiproliferative effects on MCF7 breast cancer cells and induced apoptosis in a dose-dependent manner. Molecular docking analysis revealed that saccharopine demonstrated a higher binding affinity with EGFR compared to the reference compound (17b-estradiol). The subsequent MDS simulations indicated stable binding patterns and conformation of the EGFR-saccharopine complex, suggesting a potential role in inhibiting EGFR-mediated signaling pathways. The investigation of Terminalia chebula fruit extract and its phytochemical saccharopine has revealed promising antiproliferative effects and a strong binding affinity with EGFR. These findings provide a foundation for future research aimed at isolating saccharopine and conducting in vivo studies to evaluate its potential as a targeted therapy for breast cancer. The development of novel anticancer agents from plant sources holds great promise in advancing the field of oncology and improving treatment outcomes for breast cancer patients.

Influence of Coronary Artery Bypass Grafts on Blood Aminothiols in Patients with Coronary Artery Disease.

Coronary artery disease (CAD) and the coronary artery bypass graft (CABG) are associated with a decreased blood glutathione (bGSH) level. Since GSH metabolism is closely related to other aminothiols (homocysteine and cysteine) and glucose, the aim of this study was to reveal the associations of bGSH with glucose and plasma aminothiols in CAD patients (N = 35) before CABG and in the early postoperative period. Forty-three volunteers with no history of cardiovascular disease formed the control group. bGSH and its redox status were significantly lower in CAD patients at admission. CABG had no significant effect on these parameters, with the exception of an increase in the bGSH/hemoglobin ratio. At admission, CAD patients were characterized by negative associations of homocysteine and cysteine with bGSH. All these associations disappeared after CABG. An association was found between an increase in oxidized GSH in the blood in the postoperative period and fasting glucose levels. Thus, CAD is associated with the depletion of the intracellular pool and the redox status of bGSH, in which hyperhomocysteinemia and a decrease in the bioavailability of the extracellular pool of cysteine play a role. The present study indicates that CABG causes disruptions in aminothiol metabolism and induces the synthesis of bGSH. Moreover, glucose becomes an important factor in the dysregulation of GSH metabolism in CABG.

The Role of Trace Elements and Minerals in Osteoporosis: A Review of Epidemiological and Laboratory Findings.

The objective of the present study was to review recent epidemiological and clinical data on the association between selected minerals and trace elements and osteoporosis, as well as to discuss the molecular mechanisms underlying these associations. We have performed a search in the PubMed-Medline and Google Scholar databases using the MeSH terms "osteoporosis", "osteogenesis", "osteoblast", "osteoclast", and "osteocyte" in association with the names of particular trace elements and minerals through 21 March 2023. The data demonstrate that physiological and nutritional levels of trace elements and minerals promote osteogenic differentiation through the up-regulation of BMP-2 and Wnt/ß-catenin signaling, as well as other pathways. miRNA and epigenetic effects were also involved in the regulation of the osteogenic effects of trace minerals. The antiresorptive effect of trace elements and minerals was associated with the inhibition of osteoclastogenesis. At the same time, the effect of trace elements and minerals on bone health appeared to be dose-dependent with low doses promoting an osteogenic effect, whereas high doses exerted opposite effects which promoted bone resorption and impaired bone formation. Concomitant with the results of the laboratory studies, several clinical trials and epidemiological studies demonstrated that supplementation with Zn, Mg, F, and Sr may improve bone quality, thus inducing antiosteoporotic effects.

Assessment of antimicrobial and anthelmintic activity of silver nanoparticles bio-synthesized from Viscum orientale leaf extract.

BACKGROUND: Viscum orientale is a largely used parasitic plant with traditional medicinal properties. They are considered to possess the medicinal properties of host tree which they grow on. It's a least explored plant with ethanopharmacological importance. As a result, the current work aimed to investigate the biological effects of Viscum orientale extract and silver nanoparticles (AgNPs) generated from it. METHODS: AgNPs synthesized using Viscum orientale plant extract and analysed on time dependent series and was characterized using Ultra Violet UV-visible spectra, Fourier Transform Infrared Spectroscopy FTIR, X-ray diffraction (XRD), Energy Dispersive X-ray Spectroscopy (EDX), Scanning Electron Microscopy (SEM). Further using disc method anti-microbial assay was performed following antioxidation screening using 1,1-diphenyl-2-picryl-hydrazyl (DPPH), reducing power and nitric oxide content and heamgglutination with human blood. RESULTS: On green synthesis using silver, the phyto contituents of plant Viscum orientale effectively reduced silver ions at 3-4 h of continuous stirring to form AgNPs. UV-vis spectra showed a typical peak of AgNPs at 480 nm. The FTIR analysis confirmed the covering of silver layers to bio-compounds of the extract. SEM analysis represented AgNPs as spherical morphologies ranging from 119-222 nm. AgNPs exhibited impressive zone of inhibition against Escherichia coli (8.1 ± 0.3 mm), Staphylococcus aureus (10.3 ± 0.3 mm), Bacillus subtilis (7.3 ± 0.3 mm), Bacillus cereus (8.2 ± 0.3 mm), Salmonella typhi (7.1 ± 0.2 mm). AgNps exhibited efficiency against DPPH at EC50 value of 57.60 µg/ml. and reducing power at EC50 of 53.42 µg/ml and nitric oxide scavenging of EC50 of 56.01 µg/ml concentration. Further, anthelmintic activity results showed synthesized nanoparticles significant reduction in the paralysis time to 5.4 ± 0.3 min and death time to 6.5 ± 0.6 min in contrast to the individual factors. On hemagglutination using AgNPs, above 80 µg/ml of concentration showed very significant effect on comparison with water extract. CONCLUSION: Synthesized AgNPs using Viscum orientale water extract displayed versatile biological activity than individual extract. This study has forecasted a new path to explore more on this AgNPs for further research.

Environmentally benign silver bio-nanomaterials as potent antioxidant, antibacterial, and antidiabetic agents: Green synthesis using Salacia oblonga root extract.

Introduction: The use of plant extracts in the green synthesis of metallic nanoparticles is one of the simplest, most practical, economical, and ecologically friendly methods for avoiding the use of toxic chemicals. Method: Silver nanoparticles (AgNPs) were synthesized, employing a high-efficiency, non- toxic, cost-effective, green, and simple technique that included the use of Salacia oblonga root extract (SOR) as a capping agent compared to synthetic nanoparticles. The use of S. oblonga can be seen in traditional medicines for treating diabetes, obesity, rheumatism, gonorrhea, asthma, and hyperglycemia. The objectives of the current study were to green synthesize S. oblonga root extract silver nanoparticles (SOR-AgNPs), characterize them, and study their antioxidant, antibacterial, and antidiabetic activities. Result: The shape of SOR-AgNPs was spherical, at less than 99.8 nm in size, and exhibited a crystalline peak at XRD. The green synthesized SOR-AgNPs showed significant antioxidant properties like DPPH (80.64 µg/mL), reducing power capacity (81.09 ± SEM µg/mL), nitric oxide (96.58 µg/mL), and hydroxyl (58.38 µg/mL) radical scavenging activities. The MIC of SOR-AgNPs was lower in gram-positive bacteria. The SOR-AgNPs have displayed efficient inhibitory activity against α-amylase, with an EC50 of 58.38 µg/mL. Analysis of capping protein around the SOR-AgNPs showed a molecular weight of 30 kDa. Discussion: These SOR-AgNPs could be used as antibacterial and antidiabetic drugs in the future as it is cheap, non-toxic, and environmentally friendly. Bio-fabricated AgNPs had a significant impact on bacterial strains and could be used as a starting point for future antibacterial drug development.

In Silico Computational Studies of Bioactive Secondary Metabolites from Wedelia trilobata against Anti-Apoptotic B-Cell Lymphoma-2 (Bcl-2) Protein Associated with Cancer Cell Survival and Resistance.

In the present study, the binding affinity of 52 bioactive secondary metabolites from Wedelia trilobata towards the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein (PDB: 2W3L) structure was identified by using in silico molecular docking and molecular dynamics simulation. The molecular docking results demonstrated that the binding energies of docked compounds with Bcl-2 protein ranged from -5.3 kcal/mol to -10.1 kcal/mol. However, the lowest binding energy (-10.1 kcal/mol) was offered by Friedelin against Bcl-2 protein when compared to other metabolites and the standard drug Obatoclax (-8.4 kcal/mol). The molecular dynamics simulations revealed that the Friedelin-Bcl-2 protein complex was found to be stable throughout the simulation period of 100 ns. Overall, the predicted Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of Friedelin are relatively better than Obatoclax, with the most noticeable differences in many parameters where Friedelin has no AMES toxicity, hepatotoxicity, and skin sensitization. The ADMET profiling of selected compounds supported their in silico drug-likeness properties. Based on the computational analyses, the present study concluded that Friedelin of W. trilobata was found to be the potential inhibitor of the Bcl-2 protein, which merits attention for further in vitro and in vivo studies before clinical trials.

Novel Benzimidazole Derived Imine Ligand and Its Co(III) and Cu(II) Complexes as Anticancer Agents: Chemical Synthesis, DFT Studies, In Vitro and In Vivo Biological Investigations.

The emerging interest in the field of coordination chemistry and their biological applications has created a novel impact in the field of chemical biology. With this motivation, in this work we have synthesized a novel benzimidazole derived imine ligand, 2-((E)-((1H-benzo[d]-2-yl)methylimino)methyl)-4-fluorophenol (HBMF) and its Co(III) and Cu(II) complexes. The metal complexes (C1-C4) were synthesized in 2:1 (HBMF: metal ion) and 1:1:1 (HBMF: metal ion: 1,10-phen) ratios. Structural elucidations of all the synthesized compounds were performed using FT-IR, UV-Visible, NMR, Mass spectroscopy and elemental analysis techniques. A combination of first principles calculations and molecular dynamics simulations was applied to computationally investigate the structural, reactive, and spectroscopic properties of the newly synthesized HBMF ligand and its complexes with copper and cobalt metal ions. Quantum-mechanical calculations in this study were based on the density functional theory (DFT), while molecular dynamics (MD) simulations were based on the OPLS4 force field. The DFT calculations were used to obtain the reactive and spectroscopic properties of the ligand and its complexes, while molecular dynamics (MD) simulations were used to address the ligand's reactivity with water. Further, the in vitro anti-proliferative activity of the compounds was tested against the A549, Ehrlich-Lettre ascites carcinoma (EAC), SIHA and NIH3T3 cell lines. The biological results depicted that the compound C4, with molecular formula C27H23Cl2CoFN5O3 exhibited profound anti-proliferative activity against the EAC cell line with a significant IC50 value of 10 µm when compared to its parent ligand and other remaining metal complexes under study. Various assays of hematological parameters (alkaline phosphate, creatinine, urea, RBC and WBC) were performed, and significant results were obtained from the experiments. Furthermore, the effect of C4 on neovascularization was evaluated by stimulating the angiogenesis with rVEGF165, which was compared with non-tumor models. The EAC cells were cultured in vivo and administrated with 50 and 75 mg/kg of two doses and tumor parameters were evaluated.

Integrated network pharmacology and molecular modeling approach for the discovery of novel potential MAPK3 inhibitors from whole green jackfruit flour targeting obesity-linked diabetes mellitus.

The current study investigates the effectiveness of phytocompounds from the whole green jackfruit flour methanol extract (JME) against obesity-linked diabetes mellitus using integrated network pharmacology and molecular modeling approach. Through network pharmacology, druglikeness and pharmacokinetics, molecular docking simulations, GO analysis, molecular dynamics simulations, and binding free energy analyses, it aims to look into the mechanism of the JME phytocompounds in the amelioration of obesity-linked diabetes mellitus. There are 15 predicted genes corresponding to the 11 oral bioactive compounds of JME. The most important of these 15 genes was MAPK3. According to the network analysis, the insulin signaling pathway has been predicted to have the strongest affinity to MAPK3 protein, which was chosen as the target. With regard to the molecular docking simulation, the greatest notable binding affinity for MAPK3 was discovered to be caffeic acid (-8.0 kJ/mol), deoxysappanone B 7,3'-dimethyl ether acetate (DBDEA) (-8.2 kJ/mol), and syringic acid (-8.5 kJ/mol). All the compounds were found to be stable inside the inhibitor binding pocket of the enzyme during molecular dynamics simulation. During binding free energy calculation, all the compounds chiefly used Van der Waal's free energy to bind with the target protein (caffeic acid: 102.296 kJ/mol, DBDEA: -104.268 kJ/mol, syringic acid: -100.171 kJ/mol). Based on these findings, it may be inferred that the reported JME phytocompounds could be used for in vitro and in vivo research, with the goal of targeting MAPK3 inhibition for the treatment of obesity-linked diabetes mellitus.

Exploration of Anti-HIV Phytocompounds against SARS-CoV-2 Main Protease: Structure-Based Screening, Molecular Simulation, ADME Analysis and Conceptual DFT Studies.

The ever-expanding pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has gained attention as COVID-19 and caused an emergency in public health to an unmatched level to date. However, the treatments used are the only options; currently, no effective and licensed medications are available to combat disease transmission, necessitating further research. In the present study, an in silico-based virtual screening of anti-HIV bioactive compounds from medicinal plants was carried out through molecular docking against the main protease (Mpro) (PDB: 6LU7) of SARS-CoV-2, which is a key enzyme responsible for virus replication. A total of 16 anti-HIV compounds were found to have a binding affinity greater than -8.9 kcal/mol out of 150 compounds screened. Pseudohypericin had a high affinity with the energy of -10.2 kcal/mol, demonstrating amino acid residual interactions with LEU141, GLU166, ARG188, and GLN192, followed by Hypericin (-10.1 kcal/mol). Moreover, the ADME (Absorption, Distribution, Metabolism and Excretion) analysis of Pseudohypericin and Hypericin recorded a low bioavailability (BA) score of 0.17 and violated Lipinski's rule of drug-likeness. The docking and molecular simulations indicated that the quinone compound, Pseudohypericin, could be tested in vitro and in vivo as potent molecules against COVID-19 disease prior to clinical trials.This was also supported by the theoretical and computational studies conducted. The global and local descriptors, which are the underpinnings of Conceptual Density FunctionalTheory (CDFT) have beenpredicted through successful model chemistry, hoping that they could be of help in the comprehension of the chemical reactivity properties of the molecular systems considered in this study.

Preparation, Characterization and In Vitro Biological Activities of New Diphenylsulphone Derived Schiff Base Ligands and Their Co(II) Complexes.

The present work describes the chemical preparation of Schiff bases derived from 4,4'-diaminodiphenyl sulfone (L1-L5) and their Co(II) metal complexes. The evaluation of antimicrobial and anticancer activities against MCF-7 cell line and human lung cancer cell line A-549 was performed. The aforementioned synthesized compounds are characterized by spectroscopic techniques and elemental analysis confirms successful synthesis. The results from the above analytical techniques revealed that the complexes are in an octahedral geometry. The antimicrobial activity of the synthesized Schiff base ligands and their metal complexes under study was carried out by using the agar well diffusion method. The ligand and complex interactions for biological targets were predicted using molecular docking and high binding affinities. Further, the anticancer properties of the synthesized compounds are performed against the MCF-7 cell line and human lung cancer cell line A-549 using adriamycin as the standard drug.

Prognostic Value of Histological and Immunohistochemical Data in Diabetic Foot Ulcers.

Diabetic foot ulcers are an extremely urgent medical and social problem throughout the world. The purpose of this study was to analyse the histological and immunohistochemical features of tissues and cells of different sections of wounds taken during the primary surgical treatment of chronic wounds in patients with diabetic foot syndrome with favourable and unfavourable outcomes. MATERIAL AND METHODS: A clinical prospective observational study of the treatment outcomes of fifty-three patients with diabetic foot ulcers hospitalized twice in one specialized centre over the course of the year was conducted. The analysis of histological and immunohistochemical data of the tissues of the edges and the centre of the ulcer taken during the primary surgical treatment was performed. While performing histological analyses of wound tissues, special attention was given to the determination of cellular characteristics of leukocyte-necrotic masses, granulation tissue, and loose and dense connective tissue. Immunohistochemistry was performed using a set of monoclonal antibodies, allowing verification of neutrophilic leukocytes, fibroblasts, and endothelial cells. RESULTS: Unfavourable outcomes (amputation, reamputation, death from cardiovascular diseases, nonhealing ulcer within a year) were registered in 52.8% of cases. Uniform distribution of neutrophils and endothelial cell fibroblasts in all parts of the wound was recorded in patients with a favourable outcome. An unfavourable outcome was predetermined by the uneven content of these cells with a significant increase in neutrophilic leukocytosis in the bottom of the wounds, as well as a significant decrease in the number of fibroblasts and endotheliocytes in the centre of the wounds. CONCLUSIONS: The datasets obtained during primary surgical treatment are extremely informative to predict the outcome of the treatment of diabetic foot ulcers and indicate more active surgical strategies with the potential to reduce the treatment time, increase its effectiveness, and eventually make the treatment cost-effective.

AOX1a Expression in Arabidopsis thaliana Affects the State of Chloroplast Photoprotective Systems under Moderately High Light Conditions.

Alternative oxidase (AOX) in the mitochondrial electron transport chain is considered important for sustaining photosynthesis under high light conditions. Here, we examined the effects of the AOX pathway on the state of chloroplast photoprotective systems. Arabidopsis thaliana plants (4 weeks old), comprising three genotypes (wild type [WT], overexpressing [XX-2] and antisense [AS-12] lines for AOX1a), were exposed to moderately high light conditions (MHL, 400 µmol m-2 s-1) in a short-term experiment (8 h). After 8 h of MHL, the WT and XX-2 plants showed stable non-photochemical quenching (qN) and violaxanthin cycle activity. Antisense plants displayed the lowest level of qN and a lower de-epoxidation state (DEPS) relative to plants of the same line after 4-6 h MHL, as well as compared to WT and XX-2 plants after 8 h MHL. The decline in DEPS in AS-12 plants was attributed to an insufficient violaxanthin de-epoxidase activity, which in turn was associated with a decrease in reduced ascorbate levels in the chloroplasts and leaves. Simultaneously, gene expression and the activity of ascorbate peroxidase in the antisense line increased after 8 h of MHL, supporting the compensatory effect of the antioxidant system when AOX1a expression is suppressed. This study emphasizes the role played by AOX in modulating the photoprotection processes and in the maintenance of relationships between mitochondria and chloroplasts by influencing ascorbate content.

Anticholinesterase activity of Areca Catechu: In Vitro and in silico green synthesis approach in search for therapeutic agents against Alzheimer's disease.

For many years, the primary focus has been on finding effective treatments for Alzheimer's disease (AD), which has led to the identification of promising therapeutic targets. The necessity for AD stage-dependent optimal settings necessitated a herbal therapy strategy. The plant species Areca Catechu L. (AC) was selected based on the traditional uses against CNS-related diseases. AC leaf extract were prepared using a Soxhlet extraction method and hydroxyapatite nanoparticles (HAp-NPs) were synthesized from the same (AC-HAp-NPs). Powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), selected area electron diffraction (SAED) and fourier transform infrared spectroscopy (FTIR) were used to confirm the structure and morphology of the as-prepared AC-HAp-NPs. The crystalline character of the AC-HAp-NPs was visible in the XRD pattern. The synthesized material was found to be nanoflake, with an average diameter of 15-20 nm, according to SEM analysis. The TEM and SAED pictures also revealed the form and size of AC-HAp-NPs. In vitro anti-acetylcholinesterase and butyrylcholinesterase (AChE and BChE) activities of hydroxyapatite nanoparticles produced from an AC leaf extract was tested in this study. When compared to control, AC-HAp-NPs had higher anti-AChE and BChE activity. The anti-acetylcholinesterase action of phytoconstituents generated from AC leaf extract was mediated by 4AQD and 4EY7, according to a mechanistic study conducted utilizing in silico research. The global and local descriptors, which are the underpinnings of Conceptual Density Functional Theory (CDFT), have been predicted through the MN12SX/Def2TZVP/H2O model chemistry to help in the comprehension of the chemical reactivity properties of the five ligands considered in this study. The CDFT experiments are supplemented by the calculation of several useful calculated pharmacokinetics indices, their expected biological targets connected to the bioavailability of the five ligands in order to further the goal of studying their bioactivity.

Phytoconstituents of Withania somnifera unveiled Ashwagandhanolide as a potential drug targeting breast cancer: Investigations through computational, molecular docking and conceptual DFT studies.

Breast cancer is the second most common malignancy in females worldwide and poses a great challenge that necessitates the identification of novel therapeutic agents from several sources. This research aimed to study the molecular docking and molecular dynamics simulations of four proteins (such as PDB: 6CBZ, 1FDW, 5GWK and 2WTT) with the selected phytochemicals from Withania somnifera to identify the potential inhibitors for breast cancer. The molecular docking result showed that among 44 compounds, two of them, Ashwagandhanolide and Withanolide sulfoxide have the potential to inhibit estrogen receptor alpha (ERα), 17-beta-hydroxysteroid -dehydrogenase type 1 (17ß-HSD1), topoisomerase II alpha (TOP2A) and p73 tetramerization domain that are expressed during breast cancer. The molecular dynamics (MD) simulations results suggested that Ashwagandhanolide remained inside the binding cavity of four targeted proteins and contributed favorably towards forming a stable protein-ligand complex throughout the simulation. Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties confirmed that Ashwagandhanolide is hydrophobic and has moderate intestinal permeability, good intestinal absorption, and poor skin permeability. The compound has a relatively low VDss value (-1.652) and can be transported across ABC transporter and good central nervous system (CNS) permeability but did not easily cross the blood-brain barrier (BBB). This compound does not possess any mutagenicity, hepatotoxicity and skin sensitization. Based on the results obtained, the present study highlights the anticancer potential of Ashwagandhanolide, a compound from W. somnifera. Furthermore, in vitro and in vivo studies are necessary to perform before clinical trials to prove the potentiality of Ashwagandhanolide.