In Vitro Pro-apoptotic and Anti-migratory Effects of Ficus deltoidea L. Plant Extracts on the Human Prostate Cancer Cell Lines PC3.

This study aims to evaluate the in vitro cytotoxic and anti-migratory effects of Ficus deltoidea L. on prostate cancer cells, identify the active compound/s and characterize their mechanism of actions. Two farmed varieties were studied, var. angustifolia (FD1) and var. deltoidea (FD2). Their crude methanolic extracts were partitioned into n-hexane (FD1h, FD2h) chloroform (FD1c, FD2c) and aqueous extracts (FD1a, FD2a). Antiproliferative fractions (IC50 < 30 μg/mL, SRB staining of PC3 cells) were further fractionated. Active compound/s were dereplicated using spectroscopic methods. In vitro mechanistic studies on PC3 and/or LNCaP cells included: annexin V-FITC staining, MMP depolarization measurements, activity of caspases 3 and 7, nuclear DNA fragmentation and cell cycle analysis, modulation of Bax, Bcl-2, Smac/Diablo, and Alox-5 mRNA gene expression by RT-PCR. Effects of cytotoxic fractions on 2D migration and 3D invasion were tested by exclusion assays and modified Boyden chamber, respectively. Their mechanisms of action on these tests were further studied by measuring the expression VEGF-A, CXCR4, and CXCL12 in PC3 cells by RT-PCR. FD1c and FD2c extracts induced cell death (P < 0.05) via apoptosis as evidenced by nuclear DNA fragmentation. This was accompanied by an increase in MMP depolarization (P < 0.05), activation of caspases 3 and 7 (P < 0.05) in both PC3 and LNCaP cell lines. All active plant extracts up-regulated Bax and Smac/DIABLO, down-regulated Bcl-2 (P < 0.05). Both FD1c and FD2c were not cytotoxic against normal human fibroblast cells (HDFa) at the tested concentrations. Both plant extracts inhibited both migration and invasion of PC3 cells (P < 0.05). These effects were accompanied by down-regulation of both VEGF-A and CXCL-12 gene expressions (P < 0.001). LC-MS dereplication using taxonomy filters and molecular networking databases identified isovitexin in FD1c; and oleanolic acid, moretenol, betulin, lupenone, and lupeol in FD2c. In conclusion, FD1c and FD2c were able to overcome three main hallmarks of cancer in PC3 cells: (1) apoptosis by activating of the intrinsic pathway, (2) inhibition of both migration and invasion by modulating the CXCL12-CXCR4 axis, and (3) inhibiting angiogenesis by modulating VEGF-A expression. Moreover, isovitexin is here reported for the first time as an antiproliferative principle (IC50 = 43 μg/mL, SRB staining of PC3 cells)

Problem-based learning: medical students&rsquo; perception toward their educational environment at Al-Imam Mohammad Ibn Saud Islamic University

Abdulaziz Abdulrahman Aldayel, Abdulrahman Omar Alali, Ahmed Abdullah Altuwaim, Hamad Abdulaziz Alhussain, Khalid Ahmed Aljasser, Khalid A Bin Abdulrahman, Majed Obaid Alamri, Talal Ayidh Almutairi College of Medicine, Al Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia Background: Problem-based learning (PBL) is a student-centered innovating instructional approach in which students define their learning objectives by using triggers from the problem case or scenario.Objectives: To assess undergraduate medical students&rsquo; perception toward PBL sessions and to compare their perceptions among different sex and grade point average (GPA) in the college of medicine, Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.Materials and methods: We conducted a cross-sectional study based on a self-administered anonymous online questionnaire during the first semester of the 2017&ndash;2018 academic year in IMSIU. The data were collected from male and female students of the second and third year, as well as male students of the fourth year.Results: Out of 259 students, 152 (58.7%) completed the questionnaire. The students&rsquo; perception toward PBL was more positive than negative. Most of the students reported that PBL sessions increased their knowledge of basic sciences (P=0.03). Furthermore, most students agreed that PBL provided a better integration between basic and clinical sciences which differed significantly between the different GPA groups (P=0.02). Nevertheless, only 28.3% of the students agreed that the teaching staff is well prepared to run the sessions with significant statistical difference among different GPA groups (P=0.02). Moreover, only 26.3% of the students reported that there was proper student training before starting the PBL sessions with no significant difference. Additionally, only 34.2% and 28.9% of the students felt that they learn better and gain more knowledge thorough PBL than lectures respectively, with no significant difference.Conclusion: This study showed that tutors should be trained to guide the process of PBL effectively to achieve its goals. Moreover, students should be securely introduced to PBL and experience the development of their clinical reasoning through PBL. Further improvements are needed to provide students with an effective favorable learning environment and to take the students recommendations into consideration. Keywords: medical students, problem-based learning, education, perception, curriculum &nbsp