Evaluating the therapeutic potential of amygdalin: Cytotoxic and antimicrobial properties.

Leukemia is an incurable disease; it exhibits strong resistance to chemotherapy and other therapies, and it represents the most common childhood cancer and mortality. The cytotoxic of amygdalin (AMG) against the cell line of human monocytic leukemia (THP-1) was recorded, before determining other pharmacological effects. The cells were exposed to AMG for 24 hr at 37°C at different concentrations, the cytotoxic effect was determined via the MTT assay. The cells and the supernatant were collected for analyzing the oxidant/antioxidant status, apoptotic markers, and anti-microbial activity. Results showed a marked anti-proliferative cytotoxic effect of AMG which is concentration and time-dependent, the lipid peroxidation content was significantly decreased while the total thiol was increased in the treated cell line, significant up-regulation of Caspase-3 (Cas-3) and Bcl-2-associated X protein (BAX) and down-regulation of B-cell lymphoma 2 (Bcl-2). Furthermore, The bacterial activity was detected via Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), and Disc Diffusion assays, while the antifungal evaluation was done by the Minimum Fungicidal Concentration (MFC). Antimicrobial experiments revealed that AMG exerted potent, broad-spectrum antimicrobial effects toward a diversity of dangerously infecting pathogens. In conclusion; the prevailing research suggests that AMG is an effective anticarcinogenic and antimicrobial substance. The utilization of AMG subsequently in masks or wound dressings to prevent bacterial & fungal infections, including mucormycosis following COVID-19, as well as infections caused by penicillium and aspergillus, is a highly effective strategy in combating resistant microorganisms.

Factors associated with anxiety-related symptoms in children and adolescents during COVID-19 in Oman: a cross-sectional study.

Reports from different parts of the world suggest that the COVID-19 pandemic and the resultant lockdown and social distancing measures have heralded unprecedented mental health challenges among children and adolescents. To date, there is a dearth of studies emerging from the Arabian Gulf, where the majority of its population are children and adolescents. The study aims to examine the prevalence of anxiety-related symptoms and their covariates among children and adolescents in an Arabian Gulf country, Oman. This is a cross-sectional analytic study carried out over two weeks (1st to 15th of August 2020) during the COVID-19 pandemic across Oman. Parents were asked to complete the online survey, which consisted of the parent version of the Screen for Child Anxiety Related Emotional Disorders (SCARED) instrument and questions regarding basic socio-demographic information. Logistic regression was used to identify the contributing variables associated with anxiety-related symptoms. A total of 790 valid responses were received. Among the 790 children, 33.3% (n = 263) were diagnosed with anxiety-related symptoms by the SCARED instrument. Logistic regression analysis suggested that anxiety-related symptoms in children and adolescents were significantly associated with three demographic variables. The model shows that children with divorced or separated parents were 1.9 times more likely to have anxiety-related symptoms than children of married couples (OR = 1.93, p = 0.035). Children living in families with an income below USD 1000/month, were 1.8 times more likely to have anxiety-related symptoms than a family with an income of USD 4000/month (OR = 1.833, p = 0.018). Children in grades 3-6 were 1.8 times more likely to have anxiety-related symptoms than those in grades 1-2 (OR = 1.79, p = 0.024). Anxiety-related symptoms are common among Omani children and adolescents. They are more likely to be reported in middle scholastic grade levels and children from families with marital discord and low socioeconomic status. It is not clear whether the presently observed rates of anxiety exceed the prevalence that would have been observed prior to the COVID-19 pandemic. More studies are therefore warranted using children and adolescents' self-reported scales.

Nitrogen-doped carbon quantum dots as a novel treatment for black fungal bone infections (Mucormycosis): in vitro and in vivo study.

Most fungal bone and joint infections (arthritis) are caused by Mucormycosis (Mucor indicus). These infections may be difficult to treat and may lead to chronic bone disorders and disabilities, thus the use of new antifungal materials in bone disorders is vital, particularly in immunocompromised individuals, such as those who have contracted coronavirus disease 2019 (COVID-19). Herein, we reported for the first time the preparation of nitrogen-doped carbon quantum dots (N/CQDs) and a nitrogen-doped mesoporous carbon (N/MC) using a quick micro-wave preparation and hydrothermal approach. The structure and morphology were analysed using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and surface area analyser. Minimum inhibitory concentration (MIC), disc diffusion tests, minimum fungicidal concentration (MFC) and antifungal inhibitory percentages were measured to investigate the antifungal activity of N/CQDs and N/MC nanostructures. In addition to the in vivo antifungal activity in rats as determined by wound induction and infection, pathogen count and histological studies were also performed. According to in vitro and in vivo testing, both N/CQDs with small size and N/MC with porous structure had a significant antifungal impact on a variety of bone-infecting bacteria, including Mucor infection. In conclusion, the present investigation demonstrates that functional N/CQDs and N/MC are effective antifungal agents against a range of microbial pathogenic bone disorders in immunocompromised individuals, with stronger and superior fungicidal activity for N/CQDs than N/MC in vitro and in vivo studies.

Identifying novel therapeutic inhibitors to target FMS-like tyrosine kinase-3 (FLT3) against acute myeloid leukemia: a molecular docking, molecular dynamics, and DFT study.

Around 30% of acute myeloid leukemia (AML) patients have triggering mutations in Feline McDonough Sarcoma (FMS)-like tyrosine kinase 3 (FLT3), which has been suggested as a possible therapeutic candidate for AML therapy. Many tyrosine kinase inhibitors are available and have a wide variety of applications in the treatment of cancer by inhibiting subsequent steps of cell proliferation. Therefore, our study aims to identify effective antileukemic agents against FLT3 gene. Initially, well-known antileukemic drug candidates have been chosen to generate a structure-based pharmacophore model to assist the virtual screening of 217,77,093 compounds from the Zinc database. The final hits compounds were retrieved and evaluated by docking against the target protein, where the top four compounds have been selected for the analysis of ADMET. Based on the density functional theory (DFT), the geometry optimization, frontier molecular orbital (FMO), HOMO-LUMO, and global reactivity descriptor values have been evaluated that confirming a satisfactory profile and reactivity order for the selected candidates. In comparison to control compounds, the docking results revealed that the four compounds had substantial binding energies (-11.1 to -11.5 kcal/mol) with FLT3. The physicochemical and ADMET (adsorption, distribution, metabolism, excretion, toxicity) prediction results corresponded to the bioactive and safe candidates. Molecular dynamics (MD) confirmed the better binding affinity and stability compared to gilteritinib as a potential FLT3 inhibitor. In this study, a computational approach has been performed that found a better docking and dynamics score against target proteins, indicating potent and safe antileukemic agents, furthermore in-vivo and in-vitro investigations are recommended.Communicated by Ramaswamy H. Sarma.

Antifungal Activity of Chitosan Polymeric Nanoparticles and Correlation with Their pH Against Mucor circinelloides Causing Mucormycosis, Along with Penicillium notatum and Aspergillus Species.

Mucormycosis is uncommon, yet it is more prevalent among individuals with underlying health conditions and those who are immunocompromised. Chitosan is studied because of its appealing properties and diverse applications. The purpose of this work is to synthesize chitosan nanoparticles (CSNPs) by ionic gelation method at various pH levels and test them against Mucor and other filamentous fungus. Field Emission Scanning Electron Microscope, Zeta sizer, Zeta potential, and Fourier Transformed Infrared Spectroscopy were used to characterize CSNPs. Hydrodynamic size increased considerably with increasing pH. Our CSNPs were tested against fungal isolates of Aspergillus Flavus RCMB 02783, Aspergillus Fumigatus RCMB 02564, and Aspergillus Niger RCMB 02588, Penicillium Notatum (NCPF 2881) and   (M. circinelloides CNRMA 03.894) causing mucromycosis. Antifungal activity was investigated using Minimum inhibitory concentration (MIC), Minimum Fungicidal concentration (MFC), Disc diffusion assay, and Antifungal inhibitory percentages methods. The best antifungal efficacy results were obtained through CSNPs prepared at pH = 4.4 at very low concentration for MIC (1.03 or 2.75 µg/mL) with 100% M. circinelloides inhibition followed by pH = 4.6 with MIC (73 or 208 µg/mL) and 93%  M. cirecinelloides inhibition %. Future usage of these materials in masks or wound dressing to avoid fungal infections, including mucormycosis following COVID-19, penicillium, and aspergillosis toxicity and infections.

Repro-protective activity of amygdalin and spirulina platensis in niosomes and conventional forms against aluminum chloride-induced testicular challenge in adult rats: role of CYP11A1, StAR, and HSD-3B expressions.

The male reproductive system is negatively influenced by Al exposure. Al represented a considerable hazard to men's reproduction capabilities. Amygdalin (AMG) and spirulina platensis (SP) have been considered to have a strong antioxidant and repro-protective activity; also, targeted drug delivery systems called niosomes improve the distribution of water-soluble medications like amygdalin and spirulina. Current study targeted to determine the effectiveness of AMG and SP against negative reproductive impact resulted by aluminum chloride (AlCl3) toxicity. Sixty adult male albino rats were separated into 6 groups, including the control group, which received distilled water; AlCl3 group, which received AlCl3; AMG+AlCl3 group, which received AlCl3+AMG; AMGLN+AlCl3 group, which received AlCl3+amygdalin-loaded niosomes; SP+AlCl3 group, which received AlCl3+SP; and SPLN+AlCl3 group, which received AlCl3+spirulina-loaded niosomes. All treatments were orally gavaged daily for 5 weeks, and rats were weighed weekly. At the termination of the experiment, some males (three from each group) were used for fertility traits via mating thirty virgin rat females (in a ratio of 1:2 and 2:3 male:female, respectively) followed by recording of birth weights and litter size (number of pups per each female) at birth to assess males' reproductive capability. Other males were euthanized for collection of serum, epididymal semen samples, and tissue samples for biochemical, sperm evaluation, gene expression, and histopathological measurements. There are a considerable number of negative impacts of AlCl3 on male fertility clarified by declined serum testosterone levels; an increased oxidative stress (MDA, TAC); deteriorated semen quality; down-regulation of CYP11A1, StAR, and HSD-3b gene expressions; and testicular tissue degenerative changes. In addition, litter size (number of pups per each female) and birth weights of pups obtained from mated females were affected. AMG and SP treatments, either in niosomal or conventional form, alleviated the AlCl3 negative effects by reducing oxidative stress; increasing testosterone levels; improving semen quality; upregulating of CYP11A1, StAR, and HSD-3b gene expressions; and reducing degenerative changes of testicular tissue. Besides, negative reproductive effect was diminished as observed by changes in the litter size (number of pups per each female) and birth weights of pups obtained from mated females. AMG and SP treatments (either in niosomal or conventional form), ameliorated the AlCl3 negative effects as they possess powerful antioxidant activity, as well as they have the ability to improve the reproductive activity of affected males.

Effectiveness of natural biomaterials in the protection and healing of experimentally induced gastric mucosa Ulcer in rats.

BACKGROUND: A gastric ulcer is a painful lesion of the gastric mucosa that can be debilitating or even fatal. The effectiveness of several plant extracts in the therapy of this illness has been demonstrated in traditional pharmacopoeias. AIM: this study was aimed to see if propolis, ginseng in normal or nano form, and amygdalin might help in preventing the ulcerative effects of absolute ethanol. METHODS: Gastroprotective properties of pretreatments before ethanol gavage in rats were compared to omeprazole. The ulcer and stomach parameters (ulcerated regions) were measured (mm2), ulcer inhibition percentage, the stomachs were assessed macroscopically with gastric biopsy histological examinations. RESULTS: Amygdalin, normal and nano ginseng, nano propolis followed by propolis all showed great efficacy in protecting the cyto-architecture and function of the gastric mucosa. The number of ulcerated sites was greatly reduced, and the percentage of stomach protection was increased. Histopathological examination had confirmed great protective effects of the nanoformulations followed by amygdalin. The protection and healing rate was completed to about 100% in all tested materials while ulcer areas were still partially unhealed in normal propolis and omeprazole. Quantitative assay of the m-RNA levels Enothelin 1(ET-1), leukotriene4 (LT-4), and caspase 3(Cas-3) genes and Histamine were done and revealed significant up-regulations in ethanol group and the maximum protective effect was reported with ginseng nano, moreover the histamine content was significantly decreased with nano- formulated extracts. CONCLUSION: Amygdalin and the nanoformulated ginseng and propolis had exhibited a marked protective effect against the ulcerative toxic effects of ethanol.

Development and acceptability of behavioral interventions promoting mothers' brushing of pre-school children's teeth: The preparation phase of the multi-phase optimization strategy framework.

BACKGROUND: Early childhood caries can be prevented through regular parental-supported toothbrushing, indicating the importance of behavior modification interventions targeting parents. Mobile oral health (m-oral health) interventions are gaining increased popularity although their production is not always based on solid theoretical frameworks and evidence about the efficacy of individual intervention components is not available. The Multiphase Optimization Strategy (MOST) offers a framework to develop complex m-oral health interventions and assessing the efficacy of individual components. AIM: This study describes the development and assesses the acceptability of 3 intervention components using MOST to promote mothers' brushing of their preschool children's teeth. METHODS: The Theory of Planned Behavior guided the development of 3 components: motivational interviewing (MI), storytelling videos (STVs), and oral health promotion messages (OHPMs). A researcher received training to conduct MI. Twenty-four OHPMs were developed, and 14 STVs scripts were developed based on the "And, But, Therefore" framework. A feasibility pilot study was conducted to determine the optimization objective and assess mothers' preferences regarding the frequency and timing of receiving the intervention components. The mothers participated in a semi-structured interview to assess the acceptability of the components using 7 open-ended questions based on the framework of acceptability and thematic analysis was used to analyze the qualitative data. The mothers also responded to questions assessing the perceived and experienced acceptability of the components using close-ended questions. Descriptive statistics were presented as means and standard deviations for continuous variables and median and interquartile range for categorical variables. RESULTS: Sixteen mothers were included. The mothers expressed positive affective attitude towards the interventions. They felt the components served as "good reminders" to brush their children's teeth. However, "time" was a burden for the mothers. 80% of the mothers preferred receiving the OHPMs and STVs once per week, from 8 pm to 2 am (50%), and 60% indicated they can set 15-30 min to receiving the interventions. CONCLUSION: The 3 components were acceptable to the mothers. The OHPMs and STVs will be sent to the mothers once per week, between 8 pm to 2 am. The MI and follow-up phone calls will be limited to 15 min.

Vaccination with bacterial ghosts of Streptococcus iniae and Lactococcus garvieae originated from outbreak of marine fish streptococcosis, induce potential protection against the disease in Nile tilapia, Oreochromis niloticus (Linnaeus, 1758).

Streptococcosis is an important bacterial disease affects fresh, brackish and marine fish. The disease caused annual severe economic losses in Egyptian Mari-culture. S. iniae and L. garvieae usually the main causative agents isolated. The presented study conducted to prepare bacterial ghost vaccine (BGV) candidates from isolated strains of marine streptococcosis outbreaks using NaOH chemical approach. Selected strains confirmed as pathogenic for Nile tilapia, therefore the fish selected as an experimental model. In such respect, the re-isolated S. iniae and L. garvieae were used for ghost preparations, BGVs evaluation and fish challenges. Apart of four, three fish groups namely, A, B, C designated for BGVs evaluations, while the fourth one (D) designated as control. Vaccination experiments performed via intra-peritoneal injection with 0.1 mL (1.5 × 108 CFU/mL/fish) of their corresponding BGVs twice with 2 weeks' interval; however, control fish received 0.1 mL of fish saline instead. Blood, serum, and tissue samples collected from all groups at 2 and 4 weeks post immunization (PI) for estimation of hematological, innate, and specific immune parameters. At the end, all remained fish challenged with appropriated pathogen (s) and the relative percentage of survival (RPS) calculated. Three BGVs generated namely, SiG, in addition to, novel contributions of LgG and SiLgG. Ghosts were corresponding to S. iniae, L. garvieae and their both ghost mixtures, respectively. Fish groups immunized with prepared BGVs revealed variable significant increases in PCV, GLB, PP, SOD, CAT, C5, IL-ß1, LZM, specific antibody titers and CD4 expression 2 and 4 weeks PI. MDA decreased in all vaccinated groups that was significantly with group C. Expression of MHC-II showed elevations 2 weeks PI, however, it significantly decreased at 4 weeks. The RPS recorded 90, 88.89 and 95.46% in immunized groups A, B and C, respectively. At all levels tested, obtained results proposed SiG, LgG and SiLgG as innovative vaccine candidates, which can protect cultured fish from being attacked by S. iniae, and/or L. garvieae.

Exploring the Antimicrobial Activity of Sodium Titanate Nanotube Biomaterials in Combating Bone Infections: An In Vitro and In Vivo Study.

The majority of bone and joint infections are caused by Gram-positive organisms, specifically staphylococci. Additionally, gram-negative organisms such as E. coli can infect various organs through infected wounds. Fungal arthritis is a rare condition, with examples including Mucormycosis (Mucor rhizopus). These infections are difficult to treat, making the use of novel antibacterial materials for bone diseases crucial. Sodium titanate nanotubes (NaTNTs) were synthesized using the hydrothermal method and characterized using a Field Emission Scanning Electron Microscope (FESEM), High-Resolution Transmission Electron Microscope (HRTEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), Brunauer-Emmett-Teller (BET), and Zeta sizer. The antibacterial and antifungal activity of the NaTNT framework nanostructure was evaluated using Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), Disc Diffusion assays for bacterial activity, and Minimum Fungicidal Concentration (MFC) for antifungal investigation. In addition to examining in vivo antibacterial activity in rats through wound induction and infection, pathogen counts and histological examinations were also conducted. In vitro and in vivo tests revealed that NaTNT has substantial antifungal and antibacterial effects on various bone-infected pathogens. In conclusion, current research indicates that NaTNT is an efficient antibacterial agent against a variety of microbial pathogenic bone diseases.

Insights into growth-promoting, anti-inflammatory, immunostimulant, and antibacterial activities of Toldin CRD as a novel phytobiotic in broiler chickens experimentally infected with Mycoplasma gallisepticum.

Chronic respiratory disease (CRD) caused by Mycoplasma gallisepticum (MG) leads to impaired broiler growth performance and significant economic losses worldwide. The utilization of essential oils (EOs) as natural alternatives to antibiotics to control CRD outbreaks is not completely clarified yet. Thus, we investigated the effect of a commercial EOs mixture (toldin CRD), in comparison to tilmicosin antibiotic, on the clinical observations, growth performance, immunity, digestive enzymes, gut barrier functions, and bacterial loads in broilers experimentally infected with MG. A total of 400 one-day-old broiler chicks were assigned into four groups; negative control (NC), positive control (PC), tilmicosin, and toldin CRD treated groups. All groups except NC were experimentally infected with MG at 14 d of age. Our data showed that birds treated with toldin CRD showed significant enhancement in the body weight gain (BWG) and feed conversion ratio (FCR) (P = 0.001 each) over the whole experimental period. Likely, improved digestibility and intestinal barrier functions in the toldin CRD treated group was evidenced by the significant upregulation (P < 0.05) of cholecystokinin (CCK), alpha 2A amylase (AMY2A), pancreatic lipase (PNLIP), junctional adhesion molecule-2 (JAM-2), occludin, and mucin-2 (MUC-2) genes. Moreover, toldin CRD exhibited immunostimulant and ant-inflammatory activities via significant downregulation (P < 0.05) of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 genes, significant reduction of lysozyme (LYZ), myeloperoxidase (MPO), and nitric oxide (NO) levels (P = 0.03, 0.02, and 0.001, respectively) and significant increase in the immunoglobulin G (IgG) level (P = 0.03). Notably, immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR) results showed prominent reductions (P < 0.05) in the levels of MG antigens and MG loads in the toldin CRD treated group, which were evidenced by relieving the clinical picture of MG experimental infection. In conclusion, we recommend the utilization of toldin CRD as a potential candidate for controlling MG infection in broiler chickens.

Potential of Marava arachidis, a Newly Recorded Earwig Species in Egypt as a Biological Control Agent of Rhipicephalus annulatus Tick in Laboratory.

In Egypt, only five species of Dermaptera (earwigs) have been reported. Based on both the morphological and molecular data of the earwig samples collected from a bakery in Beni-Suef, Egypt, we identified the species as Marava arachidis (Spongiphoridae), a cosmopolitan species with no prior records in Egypt. The current study was designed to analyze its predation capability on newly emerged eggs and larvae of the Rhipicephalus annulatus tick. A laboratory functional response study was set up by applying a predation test with various predator-prey ratios as treatments. This experiment was applied using the undefined mix of collected earwigs and the laboratory-collected eggs and the larvae of R. annulatus. The laboratory results showed that the mean number of predated tick eggs was 18.64 ± 11.18 in 24 h under the highest predator-prey ratio (1:10) examined, accompanied by 12.04 ± 4.38 broken but unconsumed eggs. Moreover, M. arachidis predated an average of 12.32 ± 9.07 tick larvae per day. In contrast, the mean dead larvae increased to 38.4 ± 2.30 per day with the highest predator density (1:10). The number of eggs and larvae consumed increased with the predator density. A linear relationship was detected between earwig density and the consumption rates of tick eggs (R2 = 0.99; p = 0.0001) and larvae (R2 = 0.96; p = 0.003). In conclusion, M. arachidis was first recorded in Egypt. This earwig has predation capability on R. annulatus tick eggs and larvae.

Effect of aromatic oils on the expression of some virulence-associated and antimicrobial resistance genes of Escherichia coli isolated from broilers.

Objectives: This study aimed to prove the effects of Escherichia coli isolates isolated from diseased broilers to form biofilms, describe their antimicrobial sensetivity, and determine the effect of allicin and cinnamon essential oils on the expression of some genes (fimH, int1, and luxS) through quantitative polymerase chain reaction (q-PCR). Materials and Methods: 140 samples were obtained from diseased broilers in Beni-Suef Governorate, Egypt. These samples were examined by conventional bacteriology methods to detect the causative agent. The antimicrobial susceptibility of the isolated bacteria was assessed using the disc diffusion method, The ability of yeast extract-casamino acids Congo Red Agar to generate phenotypic biofilms was next tested. The presence of resistance and virulence genes in some multidrug resistant isolates was genotypically investigated. The antibacterial effects of allicin and cinnamon oil were evaluated against the growth of multidrug-resistant E. coli. Finally, q-PCR was utilized to assess changes in some genes' expression. Results: Escherichia coli was isolated from 61 samples (43.6%). An antimicrobial susceptibility test revealed that multidrug-resistance (MDR) (could resist more than three antimicrobial classes) E. coli prevalence was 100%. 40.8% of isolates phenotypically produce biofilms. The detection of resistance and virulence genes by PCR showed that all tested isolates carry aadB, fimH, int1, qnrS, and luxS genes, while only 40% harbor iss genes. q-PCR showed that after treatment with allicin and cinnamon oils, gene expression went down. Conclusion: This investigation highlights that E. coli showed resistance against most of the tested antimicrobials; all isolates were MDR. The study showed wide dissemination of virulence and resistance genes among E. coli. Allicin and cinnamon oils have antimicrobial activities and could be used as alternatives to synthetic antimicrobial agents.

Experimental and Molecular Modeling Studies on the Complexation of Chromium(III) with the Angiotensin-Converting Enzyme Inhibitor Captopril.

Captopril (CPT) is an inhibitor of angiotensin I converting enzyme, used as a medication for the treatment of people with high blood pressure, renal insufficiency, and cardiovascular diseases. It inhibits the angiogenesis process, vasoconstriction, and tumor metastasis. Some metal-captopril complexes exhibit antimicrobial activities. In the current work, the formation of the CrIII-CPT complex was studied spectrophotometrically and potentiometrically in aqueous solution. Kinetics of CrIII-CPT complex formation was spectrophotometrically studied over the pH range 3.20-4.20, at an ionic strength of 0.3 M at 30-50 °C. CrIII-CPT complex formation was potentiometrically studied at 25 °C, where ligand protonation constants and complexes' overall stability constants were calculated. UV-vis absorption spectra were executed to confirm the complex formation. Density functional theory and molecular dynamics simulation were performed to search the geometries of the CrIII-CPT complex. Atoms in molecules and interaction region indicator calculations are used to investigate intermolecular interactions for the formation of CrIII-CPT complex. The antimicrobial activity of the CPT ligand and CrIII-CPT complex on the prevention and control of environmental pathogenic bacteria, as tested on both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative bacteria Escherichia coli (E. coli) via agar disc diffusion method, assess the ability to use as an antimicrobial agent. CPT had shown good antimicrobial activity against both types of bacteria, which had increased slightly the zone of inhibition in Cr-CPT that indicates the increased efficacy due to Cr(III) antimicrobial activity via its oxidative damage to the bacterial cell wall. No previous study tested the CPT antimicrobial activity against Gram-positive ones such as S. aureus.

Computational Identification of Druggable Bioactive Compounds from Catharanthus roseus and Avicennia marina against Colorectal Cancer by Targeting Thymidylate Synthase.

Colorectal cancer (CRC) is the second most common cause of death worldwide, affecting approximately 1.9 million individuals in 2020. Therapeutics of the disease are not yet available and discovering a novel anticancer drug candidate against the disease is an urgent need. Thymidylate synthase (TS) is an important enzyme and prime precursor for DNA biosynthesis that catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) that has emerged as a novel drug target against the disease. Elevated expression of TS in proliferating cells promotes oncogenesis as well as CRC. Therefore, this study aimed to identify potential natural anticancer agents that can inhibit the activity of the TS protein, subsequently blocking the progression of colorectal cancer. Initially, molecular docking was implied on 63 natural compounds identified from Catharanthus roseus and Avicennia marina to evaluate their binding affinity to the desired protein. Subsequently, molecular dynamics (MD) simulation, ADME (Absorption, Distribution, Metabolism, and Excretion), toxicity, and quantum chemical-based DFT (density-functional theory) approaches were applied to evaluate the efficacy of the selected compounds. Molecular docking analysis initially identified four compounds (PubChem CID: 5281349, CID: 102004710, CID: 11969465, CID: 198912) that have better binding affinity to the target protein. The ADME and toxicity properties indicated good pharmacokinetics (PK) and toxicity ability of the selected compounds. Additionally, the quantum chemical calculation of the selected molecules found low chemical reactivity indicating the bioactivity of the drug candidate. The global descriptor and HOMO-LUMO energy gap values indicated a satisfactory and remarkable profile of the selected molecules. Furthermore, MD simulations of the compounds identified better binding stability of the compounds to the desired protein. To sum up, the phytoconstituents from two plants showed better anticancer activity against TS protein that can be further developed as an anti-CRC drug.

Zn2+-Schiff's Base Complex as an "On-Off-On" Molecular Switch and a Fluorescence Probe for Cu2+ and Ag+ Ions.

The present study presents a thorough theoretical analysis of the electronic structure and conformational preference of Schiff's base ligand N,N-bis(2-hydroxybenzilidene)-2,4,6-trimethyl benzene-1,3-diamine (H2L) and its metal complexes with Zn2+, Cu2+ and Ag+ ions. This study aims to investigate the behavior of H2L and the binuclear Zn2+ complex (1) as fluorescent probes for the detection of metal ions (Zn2+, Cu2+ and Ag+) using density functional theory (DFT) and time-dependent density functional theory (TDDFT). The six conformers of the H2L ligand were optimized using the B3LYP/6-311 + + G** level of theory, while the L-2-metal complexes were optimized by applying the B3LYP functional with the LANL2DZ/6-311 + + G** mixed basis set. The gas-phase and solvated Enol-cis isomer (E-cis) was found to be the most stable species. The absorption spectra of the E-cis isomer and its metal complexes were simulated using B3LYP, CAM-B3LYP, M06-2X and ωB97X functionals with a 6-311 + + G** basis set for C, O, N and H atoms and a LANL2DZ basis set for the metal ions (Zn2+, Cu2+ and Ag+). The computational results of the B3LYP functional were in excellent agreement with the experimental results. Hence, it was adopted for performing the emission calculations. The results indicated that metal complex (1) can act as a fluorescent chemosensor for the detection of Ag+ and Cu2+ ions through the mechanism of intermolecular charge transfer (ICT) and as a molecular switch "On-Off-On" via the replacement of Cu2+ by Ag+ ions, as proved experimentally.

Band Structure Engineering and Optical Properties of Pristine and Doped Monoclinic Zirconia (m-ZrO2): Density Functional Theory Theoretical Prospective.

Recently, monoclinic ZrO2 has received great technological importance because of its remarkable dielectric properties, high chemical stability, and high melting point. Herein, we introduce first-principles calculations using the Hubbard approach (DFT + U) to study the effects of doping with Nb and W on the electronic and optical properties of pristine ZrO2. The introduction of dopant atoms into the pristine crystal structure led to the displacement of the bandgap edges and reallocation of the Fermi level. The valence band maximum (VBM) shifted upward, resulting in band gap tightening from 5.79 to 0.89 for ZrO2: Nb and to 1.33 eV for ZrO2: W. The optical absorption of doped crystals extended into the visible and near-infrared regions. Partial density of states (PDOS) calculations showed valence band dependency on the O 2p orbital energy, with the conduction band predominantly composed of Nb 4d and W 5d. For pristine ZrO2, the results obtained for the imaginary and real parts of the dielectric function, the refractive index, and the reflectivity show good agreement with the available experimental and theoretical results. For ZrO2:W, we checked the dopant location effect, and the obtained results showed no significant effect on the calculated values of the band gap with a maximum difference of 0.17 eV. Significant band gap tightening and optical properties of our systems indicate that these systems could be promising candidates for photoelectrochemical energy conversion (PEC) applications.

Synthesis, Structural Investigations, Molecular Docking, and Anticancer Activity of Some Novel Schiff Bases and Their Uranyl Complexes.

Three novel 2-aminopyrazine Schiff bases derived from salicylaldehyde derivatives and their uranyl complexes were synthesized and characterized by elemental analysis, UV-vis, FTIR, molar conductance, and thermal gravimetric analysis (TGA). The proposed structures were optimized using density functional theory (DFT/B3LYP) and 6-311G ∗(d,p) basis sets. All uranyl complexes are soluble in DMSO and have low molar conductance, which indicates that all the complexes are nonelectrolytes. The DNA binding of those Schiff bases and their uranyl complexes was studied using UV-vis spectroscopy, and screening of their ability to bind to calf thymus DNA (CT-DNA) showed that the complexes interact with CT-DNA through an intercalation mode, for which the Kb values ranged from 1 × 106 to 3.33 × 105 M-1. The anticancer activities of the Schiff base ligands and their uranyl complexes against two ovarian (Ovcar-3) and melanoma cell lines (M14) were investigated, and the results indicated that uranyl complexes exhibit better results than the Schiff base ligands. Molecular docking identified the distance, energy account, type, and position of links contributing to the interactions between these complexes and two different cancer proteins (3W2S and 2OPZ).

Mental health outcomes among health-care workers in Oman during COVID-19: A cluster analysis.

AIM: Despite the much heralded epidemic of adjustment difficulties, health-care workers (HCW), who are likely to be at risk and impacted with mental health issues, have received scant attention. This study aimed to determine whether definable profiles exist in a cohort of HCWs associated with demographic and mental health problems. METHODS: An online cross-sectional survey was conducted in Oman. Demographic and mental health data were collected from 8 to 17 April 2020. A total of 1132 participants returned their completed questionnaire. A two-step cluster analysis was used to split the sample into three clusters. RESULTS: Cluster A (n = 416) was from HCW in non-frontline roles, and constituted "low-risk and least-impacted". Cluster B (n = 412) and Cluster C (n = 304) were from frontline HCW and constituted 'high-risk and moderate-impacted' and 'high-risk and high-impacted' groups, respectively. HCWs in Cluster C reported more depression (P < 0.001), anxiety (P < 0.001), stress (P < 0.001) and clinical insomnia (P < 0.001) compared with those in the other clusters. HCWs in Cluster C were at the highest risk for mental health problems during the pandemic. CONCLUSIONS: Early psychological interventions targeting this vulnerable group may be beneficial. Management should develop different tailor-made strategic plans to address different mental health needs for each profile group.