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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.

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: 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.