Pulsatillic acid as a potential inhibitor of protein kinase C-alpha in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a global health concern with a significant impact on morbidity and mortality. Small molecule inhibitors targeting genetic mutations like EGFR and ALK have shown promise in NSCLC treatment. This study focuses on Protein Kinase C-alpha (PKCα), implicated in NSCLC pathogenesis. Overexpression of PKCα correlates with advanced disease stages. Preclinical studies suggest its inhibition can suppress NSCLC cell growth. The research employs molecular docking to identify Pulsatillic acid (PA) as a potential PKCα inhibitor. ADMET predictions support PA's candidacy and PASS analysis and Swiss Target Prediction reveal its biological properties. Fluorescence-based binding assays demonstrate PA's inhibitory potency on PKCα, aligning with molecular docking findings. Cytotoxicity assays show PA's minimal impact on HEK-293 cell viability, with an IC50 of 21.03 µM in A549 cells. mRNA expression analysis in A549 cells indicates PA's potential inhibitory effect on PKCα. In conclusion, this study highlights that PA may emerge as a promising therapeutic candidate for NSCLC, emphasizing the need for further research, validation, and exploration of its translational potential. The study contributes valuable insights into NSCLC treatment strategies, emphasizing the significance of targeting PKCα.

A Cross-Sectional Study to Assess mRNA-COVID-19 Vaccine Safety among Indian Children (5-17 Years) Living in Saudi Arabia.

The objective of this study is to assess the frequency and severity of adverse events following immunization (AEFI) in Indian children aged 5-17 years who received the Pfizer-BioNTech mRNA COVID-19 vaccine, as well as to investigate for predictors of AEFI. To examine AEFI following the first and second doses of Pfizer's vaccine, semi-structured questionnaires were distributed as Google forms at Indian schools in Saudi Arabia. The 385 responses included 48.1% male and 51.9% female children, with 136 responses of children aged 5-11 years (group A) and 249 responses from children aged 12-17 years (group B). Overall, 84.4% of children had two shots. The frequency of AEFI was reported to be higher after the first dose than after the second (OR = 2.12, 95% CI = 1.57-2.86). The reported AEFIs included myalgia, rhinitis, local reaction with fever, a temperature of 102 °F or higher, and mild to moderate injection site reactions. While group B frequently reported multiple AEFIs, group A typically reported just one. Local reaction with low grade fever was more frequently reported in group B after the first dose (24.1%) and second dose (15.4%), while local reaction without low grade fever was most frequently observed in group A after the first (36.8%) and second dose (30%). Only prior COVID-19 infection (OR = 2.98, 95% CI = 1.44-6.2) was associated with AEFI after the second dose in the study sample, whereas male gender (OR = 1.71, 95% CI = 1.13-2.6) and prior COVID-19 infection (OR = 2.95, 95% CI = 1.38-6.3) were predictors of AEFI after the first dose. Non-serious myocarditis was reported by only one child. According to the analysis conducted, the Pfizer's mRNA COVID-19 vaccination was found to be safe in Indian children.

Lasmiditan abortive therapy for episodic migraine in Phase II/III randomized clinical trials: A meta-analysis.

OBJECTIVE: Although migraine is common, there are very few treatment options. Recently, lasmiditan, a specific 5-HT1F agonist, has gained approval as abortive therapy for migraine. This meta-analysis and trial sequential analysis (TSA) was performed to analyze efficacy and tolerability of lasmiditan therapy for episodic migraine. MATERIALS AND METHODS: Phase II and Phase III double-blinded placebo-controlled randomized controlled trials (RCTs) evaluating lasmiditan for episodic migraine were searched for from electronic databases. The risk of bias was estimated, data were extracted, and relative risk (RR) were calculated for efficacy and safety outcomes with a fixed/random effect model. Forest plots and funnel plots were created. TSA graph was plotted. Therapeutic gain with lasmiditan was calculated. RESULTS: Six high-quality RCTs were included with 7122 patients. Compared to placebo, lasmiditan demonstrated a significant proportion of migraineurs reporting freedom from headache, most bothersome symptom, headache response, no disability, global impression "very much/much better" 2 h posttreatment and sustained pain freedom at 24 and 48 h with 50, 100, 200, and 400 mg doses (RR range = 1.26-2.50). 39.3% of patients in the lasmiditan group (RR = 2.43) reported one or more treatment-emergent adverse event (TEAE). Dizziness, somnolence, paresthesia, fatigue, nausea, vertigo, hypoesthesia, asthenia, muscular weakness, lethargy, and malaise had a high incidence (RR range = 3.16-12.77). Most TEAEs were mild to moderate. No vasoconstriction-related TEAE was reported. CONCLUSION: Lasmiditan demonstrated efficacy as abortive therapy for episodic migraine with central nervous system-related side effects.

The Effect of Soy Isoflavones on the Menopause Rating Scale Scoring in Perimenopausal and Postmenopausal Women: A Pilot Study.

INTRODUCTION: Menopause is associated with many unpleasant symptoms which vary in different phases of menopausal transition. Although, Hormone Replacement Therapy (HRT) is considered the most effective mode of treatment for these symptoms, its use is associated with increased risk of breast cancer, endometrial cancer and thromboembolic events. Soy isoflavones are being widely used as a safer alternative to HRT, even though scientific evidence of their efficacy is poor or lacking. AIM: To study the effect of soy isoflavone supplementation on the menopausal symptoms in perimenopausal and postmenopausal women. MATERIALS AND METHODS: An observational pilot study was done involving 29 perimenopausal and 21 postmenopausal women prescribed 100 mg soy isoflavones for 12 weeks. Menopause Rating Scale (MRS) questionnaire was administered to the patients before starting soy isoflavone therapy and at the end of treatment. Responses were analysed using Statistical Package for Social Sciences (SPSS) software 23.0. RESULTS: Total score of both the groups were comparable at baseline. Among perimenopausal women highest score was given to symptoms of psychological domain. Urogenital symptoms were the worst among postmenopausal women. After 12 weeks of treatment, total scores improved significantly by 19.55% and 12.62% in the perimenopausal and postmenopausal women respectively. The greatest improvement was seen in scores of hot flashes for both the groups and the least improvement was shown by symptoms of urogenital subscale. CONCLUSION: Soy isoflavone improves the MRS score among both the perimenopausal and postmenopausal women. As they are most effective for somatic and psychological symptoms, their use could be beneficial during perimenopause.

Use of prelecture assignment to enhance learning in pharmacology lectures for the 2nd year medical students.

OBJECTIVES: Majority of teaching hours allotted by the Medical Council of India in pharmacology are utilized in the form of didactic lecture. Although these lectures are an excellent tool to deliver the information to a large group of students, it usually ends up as a one-sided teaching session with most students being the passive listeners. To make these lectures interesting and effective, we introduced the students to prelecture assignment (PLA) in the form of clinical case before the delivery of the lecture. METHODS: This prospective educational trial was conducted in the Department of Pharmacology with undergraduate medical students in their 2nd year of their professional course. They were divided into two groups of 75 each. Group A was provided the PLA before the lecture. Group B students directly attended the lecture, sans the PLA. Multiple-choice questions-based test was conducted 2 days after the lecture. Students who failed to complete the assignment and were absent from the lecture and test were excluded from the study. Feedback from the students was obtained after the lecture. The scores in the test and responses were compiled and analyzed using Statistical Package for Social Sciences (SPSS) software version 21.0 (SPSS Inc., Chicago, IL, USA). Results were expressed in percentages and as mean ± standard deviation as applicable. P < 0.05 was considered statistically significant. RESULTS: Fifty-six students from Group A and 42 from Group B appeared for the test. The students who were given PLA scored better. They felt more confident in answering and understood the topic better than the students of other group. CONCLUSION: PLA is a useful teaching-learning tool. The pharmacology lectures are interactive, interesting, and easy to understand with this tool.