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Minichromosome maintenance complex component 7 (MCM7) is involved in replicative licensing and the synthesis of DNA, and its overexpression is a fascinating biomarker for various cancer types. There is currently no effective agent that can prevent the development of cancer caused by the MCM7 protein. However, on the molecular level, inhibiting MCM7 lowers cancer-related cellular growth. With this purpose, this study screened 452 biogenic compounds extracted from the UEFS Natural Products dataset against MCM protein by using the in silico art of technique. The hit compounds UEFS99, UEFS137, and UEFS428 showed good binding with the MCM7 protein with binding energy values of −9.95, −8.92, and −8.71kcal/mol, which was comparatively higher than that of the control compound ciprofloxacin (-6.50). The hit (UEFS99) with the minimum binding energy was picked for molecular dynamics (MD) simulation investigation, and it demonstrated stability at 30 ns. Computational prediction of physicochemical property evaluation revealed that these hits are non-toxic and have good drug-likeness features. It is suggested that hit compounds UEFS99, UEFS137, and UEFS428 pave the way for further bench work validation in novel inhibitor development against MCM7 to fight the cancers.

Lung carcinoma is the leading cause of cancer-related mortalities worldwide, and present therapeutical interventions are not successful enough to treat this disease in many cases. Recent years have witnessed a surge in exploring natural compounds for their antiproliferative efficacy to expedite the characterization of novel anticancer chemotherapeutics. Swertia chirayita is a valued medicinal herb and possess intrinsic pharmaceutical potential. However, elucidation of its anticancer effects at molecular levels remains unclear and needs to be investigated. We assessed the anticancer and apoptotic efficacy of S . chirayita ethanolic extract ( Sw -EtOH) on non-small cell lung cancer (NSCLC) A549 cells during this exploratory study. The results elucidated that S. chirayita extract induced toxic effects within lung cancer cells by ~1 fold during cytotoxicity and LDH release assay at a 400 μg/ml concentration. Sw -EtOH extract elevates the level of ROS, resulting in the disruption of Δψm and release of cytosolic cytochrome c by 3.15 fold. Activation of caspases-3, -8 & -9 also escalated by ~1 fold, which further catalyze the augmentation of PARP cleavage (~3 folds), resulting in a four-fold increase in Sw -EtOH induced apoptosis. The gene expression analysis further demonstrated that Sw -EtOH extracts inhibited JAK1/STAT3 signaling pathway by down-regulating the levels of JAK1 and STAT3 to nearly half a fold. Treatment of Sw -EtOH modulates the expression level of various STAT3 associated proteins, including Bcl-XL, Bcl-2, Mcl-1, Bax, p53, Fas, Fas-L, cyclinD1, c-myc, IL-6, p21 and p27 in NSCLC cells. Thus, our study provided a strong impetus that Sw -EtOH holds the translational potential of being further evaluated as efficient cancer therapeutics and a preventive agent for the management of NSCLC.

Objectives: Although depression symptoms are common among patients with Parkinson's disease (PD), the medical literature still reports underrecognition of depression in patients with PD. Our main objective is to examine the trend of depression recognition during the first year of PD diagnosis using large population data. Methods:We conducted a population-based study of residents in Wales, using the Secure Anonymized Information Linkage (SAIL) Databank. We included newly diagnosed patients with PD aged 40 years or older with a first PD diagnosis between 2000 and 2015. Depression and antidepressants related data were extracted from SAIL. A series of multilevel logistic regressions were run to determine the factors affecting depression recognition. The results were presented using odds ratios (ORs) with 95% confidence intervals (CI). Results:The study included 6596 patients with PD. About 38% of patients had a recorded code of antidepressants, depression diagnosis, or both within the first year of PD diagnosis. There was a significant association of depression diagnosis, antidepressant use, or both with the year of PD diagnosis (OR 0.972, 95% CI 0.962-0.983). We also found that patients who used monoamine oxidase inhibitors (MAO-B inhibitors) were associated with a lower depression diagnosis, use antidepressants, or both, compared to those who did not use MAO-B inhibitors (OR 0.769, 95% CI 0.627-0.943). Conclusion:There is a slight decrease in depression recognition in PD patients between 2000 and 2015, which could be due to an increase in depression recognition during the prodromal phase of PD.

The use of pharmaceuticals to treat Major Depressive Disorder (MDD) has several drawbacks, including severe side effects. Natural compounds with great efficacy and few side effects are in high demand due to the global rise in MDD and ineffective treatment. Yohimbine, a natural compound, has been used to treat various ailments, including neurological conditions, since ancient times. Serotonergic neurotransmission plays a crucial role in the pathogenesis of depression; thus, serotonergic receptor agonist/antagonistic drugs are promising anti-depressants. Yohimbine was investigated in this study to determine its antidepressant activity using molecular docking and pharmacokinetic analyses. Additionally, the in silico mutational study was carried out to understand the increase in therapeutic efficiency using site-directed mutagenesis. Conformational changes and fluctuations occurring during wild type and mutant serotonergic receptor, 5-hydroxytryptamine receptors 1A (5HT1A) and yohimbine were assessed by molecular dynamics MD simulation studies. Yohimbine was found to satisfy all the parameters for drug-likeness and pharmacokinetics analysis. It was found to possess a good dock score and hydrogen-bond interactions with wild type 5HT1A structure. Our findings elaborate the substantial efficacy of yohimbine against MDD; however, further bench work studies may be carried out to prove the same.

Background Antimicrobials save millions of lives annually from dying because of bacterial infections, but the rapid emergence of antimicrobial resistance (AMR) becomes a global threat. The Saudi Ministry of Health (MOH) has taken containment measures to limit the misuse of antimicrobials via implementing restrictions on dispensing without prescriptions. Hence, we aim to evaluate the impact of regulating antimicrobial sales and identify challenges that pharmacists are facing to prevent self‐medication with antimicrobial agents. Materials and Methods A cross‐sectional study was conducted using two sources of data: sales reports from 3000 pharmacies in Saudi Arabia and a self‐designed questionnaire. The questionnaire consists of 24 items written in English and Arabic languages, went through multiple steps to ensure validity and reliability and then distributed online. Descriptive analyses were used to present the results. Results A total of 106 pharmacists completed the questionnaire. Sixty‐three per cent of the respondents observed a reduction of 40% in sales, which was consistent with pharmacies’ sales reports, which revealed a 50% reduction in 2018 as compared to 2017. Seventy‐six per cent of respondents agreed that antimicrobials’ sales restrictions were frustrating to patients. The percentage of pharmacists who reported receiving prescriptions with complete information about patients, prescribers, medications and issue date was 70%, 54%, 86% and 77%, respectively. And 69% of respondents revealed receiving support from their employers to prevent dispensing antimicrobial agents without prescription. Conclusion Restriction measures implemented by the Saudi MOH led to a 40% to 50% reduction in inappropriate sales of antimicrobials. Further studies are needed to investigate the methods for improving documentation and prescribing practices.

Adenium obesum commonly known as “desert rose” belongs to the family Apopcynaceae and has previously been reported for its anti-influenza, antimicrobial, and cytotoxic efficacies and well-known for their ethno-medicinal applications. In the present study, ethanolic extracts of A. obesum (AOE) were analyzed by gas chromatography-mass spectrometry (GC–MS) to identify the important phytochemical compounds. The GC–MS analysis of AOE detected the presence of 26 phytochemical compounds. This plant is traditionally used for the treatment of various diseases. In this report, the antioxidant, anti-inflammatory, and anticancer activities of ethanolic leaf extract from A. obesum (AOE) were studied. The antioxidant potential of ethanolic extract of AOE was examined by different antioxidant assays, such as antioxidant capacity by the DPPH, ABTS, superoxide, hydroxyl radical scavenging, and lipid peroxidation inhibition assays. The antioxidant activities of various reaction mixtures of AOE were compared with a reference or standard antioxidant (ascorbic acid). In addition, we also evaluated the anticancer activity of AOE, and it was observed that AOE was found to be cytotoxic against A549 lung cancer cells. It was found that AOE inhibited the viability of A549 lung cancer cells by inducing nuclear condensation and fragmentation. Furthermore, ethanolic AOE demonstrated the anti-inflammatory potential of AOE in murine alveolar macrophages (J774A.1) as an in vitro model system. AOE showed its potential in reducing the levels of inflammatory mediators including the proinflammatory cytokines and TNF-α. The results obtained in the present investigation established the antioxidant, anticancer, and anti-inflammatory potency of AOE, which may account for subsequent studies in the formulation of herbal-based medicine.

In 2019, the Saudi Pharmacist Licensure Examination (SPLE) was first administered to all pharmacy graduates and served as one of the prerequisites for obtaining a pharmacist license. The objective of this study was to evaluate whether institution and applicant characteristics are associated with first-time SPLE success. Passing status for 2284 SPLE first-time applicants was obtained from online public data for the years 2019 and 2020. The data included applicant sex, institution type (public vs. private), and college establishment year (2006 or earlier vs. after 2006). Overall, the SPLE first-time pass rate in 2020 was significantly higher than in 2019 (98.0 vs. 95.9%; p = 0.0062). Applicants from pharmacy colleges established in or before 2006 had a higher SPLE first-time pass rate, compared to those from pharmacy colleges established after 2006 (98.2 vs. 95.2%; p < 0.0001). The pass rate for male applicants was lower compared to female applicants (95.8 vs. 97.5%; p = 0.0221). The results of logistic regression showed that exam year (2020 vs. 2019), applicant sex (female vs. male), and pharmacy college establishment year (≤2006 vs. >2006) were statistically significant predictors. Further studies are needed in the upcoming years when more cumulative data are available.