Targeted Drug Administration onto Cancer Cells Using Hyaluronic Acid-Quercetin-Conjugated Silver Nanoparticles.

Quercetin (QtN) displays low systemic bioavailability caused by poor water solubility and instability. Consequently, it exerts limited anticancer action in vivo. One solution to increase the anticancer efficacy of QtN is the use of appropriate functionalized nanocarriers that preferentially target and deliver the drug to the tumor location. Herein, a direct advanced method was designed to develop water-soluble hyaluronic acid (HA)-QtN-conjugated silver nanoparticles (AgNPs). HA-QtN reduced silver nitrate (AgNO3) while acting as a stabilizing agent to produce AgNPs. Further, HA-QtN#AgNPs served as an anchor for folate/folic acid (FA) conjugated with polyethylene glycol (PEG). The resulting PEG-FA-HA-QtN#AgNPs (further abbreviated as PF/HA-QtN#AgNPs) were characterized both in vitro and ex vivo. Physical characterizations included UV-visible (UV-Vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), particle size (PS) and zeta potential (ZP) measurements, and biopharmaceutical evaluations. The biopharmaceutical evaluations included analyses of the cytotoxic effects on the HeLa and Caco-2 cancer cell lines using the MTT assay; cellular drug intake into cancer cells using flow cytometry and confocal microscopy; and blood compatibility using an automatic hematology analyzer, a diode array spectrophotometer, and an enzyme-linked immunosorbent assay (ELISA). The prepared hybrid delivery nanosystem was hemocompatible and more oncocytotoxic than the free, pure QtN. Therefore, PF/HA-QtN#AgNPs represent a smart nano-based drug delivery system (NDDS) and could be a promising oncotherapeutic option if the data are validated in vivo.

RhoA/ROCK inhibition attenuates endothelin-1-induced glomerulopathy in the rats.

Endothelin-1 (ET-1) contributes to the development of kidney diseases. However, the underlying molecular mechanism is largely undefined. Here we sought to investigate the potential role of ET-1 receptors, ETA and ETB in the regulation of increased glomerular permeability and underlying signaling pathways post-ET-1 infusion. Male Sprague-Dawley rats were infused with ET-1 (2 pmol/kg per minute, i.v.) for four weeks, and the effect on glomerular permeability to albumin (Palb) and albuminuria was measured. The selective ROCK-1/2 inhibitor, Y-27632, was administered to a separate group of rats to determine its effect on ET-1-induced Palb and albuminuria. The role of ETA and ETB receptors in regulating RhoA/ROCK activity was determined by incubating isolated glomeruli from normal rats with ET-1 and with selective ETA and ETB receptor antagonists. ET-1 infusion for four weeks significantly elevated Palb and albuminuria. Y-27632 significantly reduced the elevation of Palb and albuminuria. The activities of both RhoA and ROCK-1/2 were increased by ET-1 infusion. Selective ETB receptor antagonism had no effect on the elevated activity of both RhoA and ROCK-1/2 enzymes. Selective ETA receptor and combined ETA/ETB receptors blockade restored the activity of RhoA and ROCK-1/2 to normal levels. In addition, chronic ET-1 infusion increased the levels of glomerular inflammatory and fibrotic markers. These effects were all attenuated in rats following ROCK-1/2 inhibition. These observations suggest that ET-1 contributes to increased albuminuria, inflammation, and fibrosis by modulating the activity of the ETA-RhoA/ROCK-1/2 pathway. Selective ETA receptor blockade may represent a potential therapeutic strategy to limit glomerular injury and albuminuria in kidney disease.

Measuring the Effectiveness of Faculty Feedback on the use of an active integrated instructional pedagogy for the embryology course.

OBJECTIVES: Didactic time-honoured teaching pedagogies carry a low educational impact due to their inability to foster active learning. Active participation from learners is considered to enhance their learning experience. Furthermore, constructive feedback has been found to facilitate active learning. This study aims to measure the impact of interventions via the use of active learning and feedback on the academic performance of medical students. METHODS: We conducted an observational multi-stage prospective study of the medical students undertaking embryology courses via passive learning (90 students), active integrated learning (80 students), and finally, with active learning and effective feedback (85 students) over three successive years. The students' grades in the formative and summative assessments were compared with their end-of-course grades. Additionally, the students' perceptions about the courses were analysed using a self-constructed questionnaire. RESULTS: A total of 255 students participated in this research. The observed frequencies of the students' responses showed significant variations in their responses to all the statements (X 2 , p < 0.0001). There was a positive trend towards the interventions carried out via active learning as well as feedback. Students' active participation increased from 24% to 69%, and finally to 72% across three years. Furthermore, students were motivated to attend sessions, as can be seen in the participation rates of 28%, 70%, and 82%, respectively. There was a significant improvement in academic grades across the three years (p values of 0.000, 0.000, and 0.006, respectively). CONCLUSION: This study validates the effectiveness of active learning and feedback on the academic performance of medical students. It is possible for an educational approach of active integrated learning followed by feedback to be embedded in the medical curricula.

Effectiveness of the team-based learning (TBL) strategy on medical students' performance.

OBJECTIVES: Team-based learning (TBL) represents a new and interesting educational strategy. It helps to enhance students' professional competencies and ideally works to prepare them in their pursuit of lifelong learning. The aim of this study is to evaluate the effectiveness of TBL as an educational strategy on medical students' performance in a problem-based learning (PBL) curriculum. METHODS: A cross-sectional study was conducted through a self-designed questionnaire. It was constructed to examine several aspects of TBL, including cognition, social skills, high school educational system, and personal development. A total of 112 students were invited to participate in the study and 100 completed the survey. Individual-readiness assurance test (IRAT) and group-readiness assurance test (GRAT) scores were collected and the data were analysed and compared to the results of the final assessment using Statistical Package for the Social Sciences (SPSS). RESULTS: A total of 52 students (52%) described TBL as fostering a cooperative learning environment and 64 students (64%) found the materials to be easier to understand when discussed among themselves as a group. Compared to final examination results, there was a significant correlation (p = 0.0001) between IRAT performance and final exam score. In addition, there was a significant correlation between high school education system and IRAT score, where the best performance was observed among students coming from schools using the British curriculum. CONCLUSIONS: The overall perception and attitude of students toward the TBL system was positive and promising. Nevertheless, there are some notes and areas of concern that must be re-examined and remedied to improve TBL as an educational tool.

Renal protective effects of arjunolic acid in a cisplatin-induced nephrotoxicity model.

Cisplatin is the first platinum-containing anti-cancer drugs. Cisplatin notable side effect of nephrotoxicity limits its use in clinic. Meanwhile, arjunolic acid possesses anti-inflammatory properties and plays protective roles against chemically induced organ pathophysiology. This study was conducted to find out whether arjunolic acid could attenuate kidney damage in rats, and to elucidate its possible mechanism of action. Fifty rats were treated with cisplatin (10mg/kg) in the presence/absence of 100 or 250mg/kg arjunolic acid. Arjunolic acid is given 1h after cisplatin. Morphological changes were assessed in kidney sections stained with Hematoxylin/Eosin and Masson Trichrome. Kidney samples were used for measurements of transforming growth factor (TGF)-ß1 and its type 1 receptor (TGF-ßR1), tumor necrosis factor (TNF)-α and interleukin (IL)-1ß by ELISA. Gene expression NFκB was determined by real time-PCR. Kidney tissue apoptosis was assessed by measuring the activities of caspase-3/8/9. The renal protective effect of arjunolic acid was confirmed by approximately normal appearance of renal tissue and the relatively unaffected serum creatinine and urea levels. Furthermore, arjunolic acid showed dose dependent reduction in cisplatin-induced elevation in renal levels of TGF-ßR1, TGF-ß1, TNF-α, IL-1ß and caspases. These findings demonstrated that arjunolic acid attenuates cisplatin nephrotoxicity either indirectly by enhancing body antioxidant activity or directly through several mechanisms, including inhibition of pro-inflammatory cytokines, blocking activation of TGF-ß1, and anti-apoptotic effects.