Design, Synthesis, and Biological Evaluation of New Potential Unusual Modified Anticancer Immunomodulators for Possible Non-Teratogenic Quinazoline-Based Thalidomide Analogs.

Sixteen new thalidomide analogs were synthesized. The new candidates showed potent in vitro antiproliferative activities against three human cancer cell lines, namely hepatocellular carcinoma (HepG-2), prostate cancer (PC3), and breast cancer (MCF-7). It was found that compounds XII, XIIIa, XIIIb, XIIIc, XIIId, XIVa, XIVb, and XIVc showed IC50 values ranging from 2.03 to 13.39 µg/mL, exhibiting higher activities than thalidomide against all tested cancer cell lines. Compound XIIIa was the most potent candidate, with an IC50 of 2.03 ± 0.11, 2.51 ± 0.2, and 0.82 ± 0.02 µg/mL compared to 11.26 ± 0.54, 14.58 ± 0.57, and 16.87 ± 0.7 µg/mL for thalidomide against HepG-2, PC3, and MCF-7 cells, respectively. Furthermore, compound XIVc reduced the expression of NFκB P65 levels in HepG-2 cells from 278.1 pg/mL to 63.1 pg/mL compared to 110.5 pg/mL for thalidomide. Moreover, compound XIVc induced an eightfold increase in caspase-8 levels with a simultaneous decrease in TNF-α and VEGF levels in HepG-2 cells. Additionally, compound XIVc induced apoptosis and cell cycle arrest. Our results reveal that the new candidates are potential anticancer candidates, particularly XIIIa and XIVc. Consequently, they should be considered for further evaluation for the development of new anticancer drugs.

Design, Synthesis, Molecular Modeling and Anti-Hyperglycemic Evaluation of Quinazoline-Sulfonylurea Hybrids as Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) and Sulfonylurea Receptor (SUR) Agonists.

New quinazoline-sulfonylurea hybrids were prepared and examined for their in vivo anti-hyperglycemic activities in STZ-induced hyperglycemic rats using glibenclamide as a reference drug. Compounds VI-6-a, V, IV-4, VI-4-c, IV-6, VI-2-a, IV-1, and IV-2 were more potent than the reference glibenclamide. They induced significant reduction in the blood glucose levels of diabetic rats: 78.2, 73.9, 71.4, 67.3, 62, 60.7, 58.4, and 55.9%, respectively, while the reference glibenclamide had 55.4%. Compounds IV-1, VI-2-a, IV-2, V, and IV-6 showed more prolonged antidiabetic activity than glibenclamide. Moreover, molecular docking and pharmacokinetic studies were performed to examine binding modes of the prepared compounds against peroxisome proliferator-activated receptor gamma (PPARγ). The highest active compounds exhibited good binding affinity with high free energy of binding against PPARγ. In silico absorption, distribution, metabolism, elimination and toxicity (ADMET) studies were performed to investigate pharmacokinetics and safety of the synthesized compounds. They showed considerable human intestinal absorption with low toxicity profile.

Medical students' attitudes toward sleeping pill usage: A cross-sectional study.

Medical students experience significant stress, which may interfere with their sleeping routines; consequently, they are at a higher risk of misusing sleeping pills. Therefore, this cross-sectional convenience sampling study aims to evaluate medical students' attitudes toward the usage of sleeping pills, as well as the prevalence of their misuse and the associated factors. A self-administered online questionnaire survey was completed by 338 medical students at the College of Medicine of the King Saud bin Abdulaziz University for Health Sciences. Of 338 participants, 84 (24.85%) reported using sleeping pills. The prevalence of sleeping pill misuse was 26.63% (n = 90). The most common misuse behavior of sleeping pills was self-prescription (n = 72, 21.30%). The factors associated with sleeping pill misuse were stimulants usage (n = 69, 92%, p = 0.0072), high grade point average (n = 63, 84%, p = 0.046), preclinical years (n = 52, 69.3%, p = 0.042), and longer average time required to fall asleep (n = 53, 70.7%, p = 0.008). The prevalence of sleeping pill misuse is high among medical students, particularly among those in preclinical years. Therefore, enhancing awareness regarding sleeping pill misuse is crucial. This can be achieved through campaigns, workshops, and providing information regarding the dangers of sleeping pill misuse in the curriculum.

Characteristics of First Cases of Coronavirus Disease 2019 and the Effort to Prevent the Early Spread of COVID-19 in Saudi Arabia.

PURPOSE: To characterize the overall trends in early cases of COVID-19 and to identify the key points of the government effort to minimize the infection. PATIENTS AND METHODS: A retrospective review and data were retrieved through online sources and the Saudi Ministry of Health daily announcements that were available online. The data included the number of infections per day, and the gender, nationality, location, source of infection, incidence, rate of recovery, and the rate mortality of COVID-19 patients in Saudi Arabia between March 1 and March 16, 2020. RESULTS: The incidence of COVID-19 increased in the first two weeks in Saudi Arabia, from zero cases on March 1 to more than 15 cases per day on March 16, with a total of 133 cases. The majority of patients were males (54.9%), of Saudi descent (54.9%), and had travel as their source of infection (57.1%). Most of the cases were in Makah (37.6%); however, there were increases in cases in all cities. Moreover, the Saudi government enacted several steps to minimize the spreading of infection. There was no statistical significance between source of infection with gender (p = 0.323). However, there was statistical significance between source of infection and nationality (p < 0.001). CONCLUSION: The incidence of COVID-19 cases is expected to continue to increase. However, the efforts of the Saudi government are crucial in minimizing the spread of this infection.

Effects of Annona muricata Extract on Triple-Negative Breast Cancer Cells Mediated Through EGFR Signaling.

PURPOSE: To evaluate the antiproliferative activity and the mechanisms of action of Annona muricata ethyl acetate (AMEA) extract and one of its active fractions on BT-20 TNBC cells. METHODS: The triple-negative human breast cancer BT-20 cells were used. After the preparation and extraction of Annona muricata ethyl acetate (AMEA), the ethyl acetate extract was exposed to a preparative thin layer chromatography (TLC) plate. From this preparative TLC plate, eight individual bands were collected. Each band was scraped and removed from the plate and soaked in ethyl acetate. After filtration, all eight fractions were then tested on the BT-20 TNBC cells using the MTS cell viability assay. The expressions of EGFR, p-EGFR, AKT, p-AKT, MAPK, p-MAPK, cyclin D1, and NF-κB p65 were measured using Western blot analysis. RESULTS: The AMEA showed a significant decrease in NF-κB p65 protein expression and BT-20 cell viability, as determined via the MTS assay. Furthermore, the AMEA was subjected to preparative thin layer chromatography (TLC), and eight fractions were obtained. From the eight fractions, only fraction 4 (F4) showed a significant reduction in cell viability in the MTS assay. Immunoblotting analysis revealed that AMEA and F4 formed an antiproliferative effect. These effects were complemented by a downregulation of cyclin D1 assembly, causing cell-cycle arrest at the G1/S phase. Furthermore, NF-κB was measured because of its involvement in the progression of cancers. CONCLUSION: The antiproliferative influence is produced through EGFR-mediated signaling pathways, which include AKT, MAPK, NF-κB, and cyclin D1 inhibition. Further studies will be required to demonstrate the possible applications of this natural product in breast cancer therapy.

Omega-3 Fatty Acids Effects on Inflammatory Biomarkers and Lipid Profiles among Diabetic and Cardiovascular Disease Patients: A Systematic Review and Meta-Analysis.

The purpose of this systematic review and meta-analysis was to investigate omega-3 fatty acids' influence on 12 inflammatory biomarkers-LDL, HDL, total cholesterol, TG, HbA1c, Apo AI, Apo AII, Apo B, CRP, TNF-α, glucose, and fasting blood glucose among diabetic and cardiovascular disease (CVD) patients. We searched articles in six database engines, and 16 of the 696 articles reviewed met the inclusion criteria. Among these, lipid and inflammatory biomarkers investigated commonly included total cholesterol (11 studies), LDL, and TG (10 studies each). Overall, omega-3 was associated with a significant reduction in Apo AII among diabetic patients, as compared to different controls (-8.0 mg/dL 95% CI: -12.71, -3.29, p = 0.0009), triglycerides (-44.88 mg/dL 95% CI: -82.6, -7.16, p < 0.0001), HDL (-2.27 mg/dL 95% CI: -3.72, -0.83, p = 0.002), and increased fasting blood glucose (16.14 mg/dL 95% CI: 6.25, 26.04, p = 0.001). Omega-3 also was associated with increased LDL among CVD patients (2.10 mg/dL 95% CI: 1.00, 3.20, p = 0.0002). We conclude that omega-3 fatty acids may be associated with lower inflammatory biomarkers among diabetic and cardiovascular patients. Clinicians should be aware of these potential benefits; however, it is essential to recommend that patients consult with clinicians before any omega-3 intake.

Is there a relationship between periodontal conditions and number of medications among the elderly?

OBJECTIVE: To investigate possible correlations of clinical attachment level and pocket depth with number of medications in elderly individuals. METHODS: Intra-oral examinations for 139 patients visiting Tufts dental clinic were done. Periodontal assessments were performed with a manual UNC-15 periodontal probe to measure probing depth (PD) and clinical attachment level (CAL) at 6 sites. Complete lists of patients' medications were obtained during the examinations. Statistical analysis involved Kruskal-Wallis, chi square and multivariate logistic regression analyses. RESULTS: Age and health status attained statistical significance (p< 0.05), in contingency table analysis with number of medications. Number of medications had an effect on CAL: increased attachment loss was observed when 4 or more medications were being taken by the patient. Number of medications did not have any effect on periodontal PD. In multivariate logistic regression analysis, 6 or more medications had a higher risk of attachment loss (>3mm) when compared to the no-medication group, in crude OR (1.20, 95% CI:0.22-6.64), and age adjusted (OR=1.16, 95% CI:0.21-6.45), but not with the multivariate model (OR=0.71, 95% CI:0.11-4.39). CONCLUSION: CAL seems to be more sensitive to the number of medications taken, when compared to PD. However, it is not possible to discriminate at exactly what number of drug combinations the breakdown in CAL will happen. We need to do further analysis, including more subjects, to understand the possible synergistic mechanisms for different drug and periodontal responses.

Effect of dried California Mission figs on mineral status and food replacement.

OBJECTIVE: Figs are a rich source of several different minerals and fibres. We studied the effect of the consumption of dried California Mission figs on mineral and nutrient levels, as well as the effect of the addition of figs to a self-selected habitual diet on dietary patterns. DESIGN: A crossover randomized controlled trial study design in which participants with a mean of age of approximately 56 years were randomly assigned to eat either their usual diet for 5 weeks or to add dried California Mission figs (120 g/d) to their usual diet for 5 weeks, after which they crossed over to the other group for an additional 5 weeks. Six 24 h dietary recalls and four blood samples were obtained from each participant. SETTING: Loma Linda University School of Public Health, USA. SUBJECTS: A follow-up study using data collected from eighty-eight American males and females from September to December 2008. RESULTS: Diets reported in the 24 h dietary recall during the fig-supplemented diet period were significantly higher in Ca and K in the dietary and total phase (P value<0·05). Nevertheless, data on mineral levels in the body gathered by means of biochemical analyses from blood samples were nearly the same for both the figs-added and the participants' standard diet. The estimated displacement suggests that eating figs resulted in the elimination of 4% of desserts, 5% of vegetables, 10% of dairy products, 23% of grain products and 168% of beverages from other sources that participants would otherwise consume. CONCLUSIONS: Based on 24 h dietary recalls, the daily consumption of figs may increase the intake of several different minerals. However, mineral levels in blood samples were not altered significantly.