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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.

Introduction As the number of unemployment among pharmacy graduates increases, the Saudi Ministry of Labor implemented extra measures to facilitate their training and hiring by the private sectors. Nevertheless, there is a paucity of data regarding pharmacy graduates’ work readiness (WR). Hence, we aim to assess their WR and identify predicting factors associated with WR among pharmacy graduates’ in Saudi Arabia. Methods A 46-item self-reported pre-validated anonymous work readiness scale (WRS) survey with a 5-point Likert scale was administered to pharmacy senior students and graduates using Qualtrics XM® survey tool over the month of May 2020. The main outcome was to assess WRS for pharmacy interns and graduates and identify factors associated with work readiness. Results A total of 617 participants have participated in this survey, out of which 46.5% were freshly graduated pharmacists and 19.6% were pharmacy interns. Most participants (82.3%) were PharmD candidates or graduates. Around two-third of participants (63%) have successfully completed all survey items. The maximum points scored was 223 out of 230, and the median overall score was found to be 175. There was no significant association with gender, age, or type of university regarding overall scores. However, a statistically significant odds ratio was observed with PharmD program type and previous pharmaceutical marketing training (OR = 1.778, 95% CI = 1.143–2.765: OR = 0.618, 95% CI = 0.432–0.884, respectively). Conclusion The overall median score shows a good work readiness level among pharmacy students/graduates in Saudi Arabia; however, PharmD program graduates exposed to advance pharmacy training, including the pharmaceutical marketing experience, have higher work readiness odds than Bpharm graduates. Further studies involving other related perspectives, such as stakeholders, employers, and preceptors, would give a clear image of pharmacy graduates’ job readiness levels.

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.

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 −8.71 kcal/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.

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., Our main objective is to examine the trend of depression recognition during the first year of PD diagnosis using large population data. The study included 6596 patients with PD, of whom 38% of patients had a recorded code of antidepressants, depression diagnosis, or both within the first year of PD diagnosis. The results shows that 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.

Mycobacterium tuberculosis (Mtb) is a deadly tuberculosis (TB)-causing pathogen. The proteasome is vital to the survival of Mtb and is therefore validated as a potential target for anti-TB therapy. Mtb resistance to existing antibacterial agents has enhanced drastically, becoming a worldwide health issue. Therefore, new potential therapeutic agents need to be developed that can overcome the complications of TB. With this purpose, in the present study, 224,205 natural compounds from the ZINC database have been screened against the catalytic site of Mtb proteasome by the computational approach. The best scoring hits, ZINC3875469, ZINC4076131, and ZINC1883067, demonstrated robust interaction with Mtb proteasome with binding energy values of −7.19, −7.95, and −7.21 kcal/mol for the monomer (K-chain) and −8.05, −9.10, and −7.07 kcal/mol for the dimer (both K and L chains) of the beta subunit, which is relatively higher than that of reference compound HT1171 (−5.83 kcal/mol (monomer) and −5.97 kcal/mol (dimer)). In-depth molecular docking of top-scoring compounds with Mtb proteasome reveals that amino acid residues Thr1, Arg19, Ser20, Thr21, Gln22, Gly23, Asn24, Lys33, Gly47, Asp124, Ala126, Trp129, and Ala180 are crucial in binding. Furthermore, a molecular dynamics study showed steady-state interaction of hit compounds with Mtb proteasome. Computational prediction of physicochemical property assessment showed that these hits are non-toxic and possess good drug-likeness properties. This study proposed that these compounds could be utilized as potential inhibitors of Mtb proteasome to combat TB infection. However, there is a need for further bench work experiments for their validation as inhibitors of Mtb proteasome.

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.

Background Resistance to antibiotics causes negative impact on health of the patients. Antibiotic resistance is the major global concern that has to be nullified for the better health outcome. The knowledge on antibiotics is very essential for the students who undertake pharmacy and health science courses. Hence a study was aimed to assess the level of knowledge, attitude, perception and practice on antibiotics usage among the pharmacy students of King Khalid University, KSA. Materials and methods A prospective online questionnaire based survey was carried out among the pharmacy students about knowledge, attitude perception and practice of antibiotics using 5-point "Likert scale" and true/false responses. The responses range from strongly agree to strongly disagree, and always to never were recorded. The data were analysed by using simple descriptive statistics. Results Out of 300 students approached 212 responded and the response rate was found to be 71%. In this study, most (95%) of the students were aware of the emerging problem of antibiotic resistance due to inappropriate use of antibiotics. Majority (89%) of the students agreed the inappropriate use of antibiotics can increase the overall cost of treatment. However, over half of the (54%) students were not aware of the antibiotic resistance that may be a nation-wide problem of Kingdom of Saudi Arabia. The net positive response (NPR) and net other response (NOR) of all items in perception on antibiotics received more or less equal responses. Conclusion The knowledge of antibiotics usage among the students are considerably good compared with previous studies. However, the attitude, perception and practice on antibiotics usage among the pharmacy students are very poor. It alarms the need of appropriate education to enlighten antibiotic awareness for the better disease prevention and health outcomes for the benefit of patient community.

Background: Acute decompensated heart failure (ADHF) is associated with a high rate of hospital readmission. The aim of this study is to examine the effect of the discharge diuretic dose compared with the home diuretic dose on hospital readmission in patients with ADHF. Methods: A single center retrospective cohort study included patients with a confirmed diagnosis of ADHF with an ejection fraction of less than 40%. The sample was divided in two groups. The first group received a total daily discharge diuretic dose that was greater than the home dose; the second group received a daily discharge diuretic that was equal to or less than the home dose. The primary outcome was all-cause 30-day readmission rate. The secondary outcomes were all-cause 60-day and 90-day readmission rates. Results: A total of 206 patients met inclusion criteria; 117 patients received a higher loop diuretic dose at discharge, while 89 were discharged with a loop diuretic that was equal to or less than the home dose. Patients in the increased-dose group had an all-cause 30-day readmission rate of 20.5% compared with 37.1% of patients with equal or reduced-dose group; P = .007. Additionally, there were lower readmission rates in 60 and 90 days between the increased and equal or reduced groups (33.3% versus 52.8%, P < .017, and 41.0% versus 62.9%, P < .003, respectively. Conclusions: Among patients admitted to hospital with ADHF and reduced ejection fraction, a discharge loop diuretic dose higher than the home dose was associated with decreased all-cause 30-day, 60-day, and 90-day readmission rates.