Introduction: The COVID-19 pandemic imposed dramatic changes on educational practices worldwide. Many universities and schools have moved into the delivery of their courses and educational programs utilizing fully electronic online modes. This study aims to evaluate the pharmacy student distance online learning experience during the COVID-19 pandemic. Methods: A cross-sectional survey was utilized where a 3-domain survey questionnaire focused on preparedness, attitude and barriers was distributed to students at the time of conclusion of the semester. Each domain consists of multiple questions that made up a score that reflects their preparedness, attitude as well as barriers relevant to distance online learning experience. The survey was voluntarily, and all data were collected and recorded via google forms with maintaining anonymity. Results: The response rate was about 75% (n = 309). The results’ analysis revealed no gender differences in any of these domains. However, there were some variable responses among different educational levels. The average preparedness score was 32.8 ± 7.2 (Max 45), the average attitude score was 66.8 ± 16.6 (Max 105), and the average barrier score was 43.6 ± 12.0 (Max 75). There was statistical significance difference in both preparedness score and attitude scores between different professional years ( P-value <.05). However, there was no difference in barrier scores among all professional years. The results indicated that about 61.4% of the students agreed on that college of pharmacy was well-prepared and ready for the online education during the emerging COVID-19 pandemic with complete transition into online education. The results also indicated that 49.2% of the students showed positive attitude toward the provided online learning. The results indicated that about 34% of the students identify some barriers toward the provided online learning. Finally, there were strong association between the need for training on how to receive online courses and preparedness and barriers scores. Discussion and conclusion: E-learning experience pose challenges and presents opportunities during emergency situations. The need for training for students and faculty was highly associated with the preparedness and barriers domains rather than the infrastructure or computer literacy, so the school can improve their experience by addressing these needs.

Background:The significance of Pak1 in prostate cancer remains unclear. Results: Pak1 knockdown impaired prostate tumor growth via increased expression of TGF␤ and reduced secretion of MMP9. Conclusions:We demonstrated that Pak1 is a more potent mediator of prostate cancer cell migration and tumor growth than Pak6, the predominant isoform in the prostate. Significance: A novel role of Pak1 in prostate cancer is identified.

Transforming growth factor beta (TGFβ) is believed to play a dual role in prostate cancer. Molecular mechanism by which TGFβ1 suppresses early prostate tumor growth and induces epithelial-to-mesenchymal transition (EMT) in advanced stages is not known. We determined if P21-activated kinase1 (Pak1), which mediates cytoskeletal remodeling is necessary for the TGFβ1 induced prostate cancer EMT. Effects of TGFβ1 on control prostate cancer PC3 and DU145 cells and those with IPA 3 and siRNA mediated Pak1 inhibition were tested for prostate tumor xenograft in vivo and EMT in vitro. TGFβ1 inhibited PC3 tumor xenograft growth via activation of P38-MAPK and caspase-3, 9. Long-term stimulation with TGFβ1 induced PC3 and DU145 cell scattering and increased expression of EMT markers such as Snail and N-cadherin through tumor necrosis factor receptor-associated factor-6 (TRAF6)-mediated activation of Rac1/Pak1 pathway. Selective inhibition of Pak1 using IPA 3 or knockdown using siRNA both significantly inhibited TGFβ1-induced prostate cancer cell EMT and expression of mesenchymal markers. Our study demonstrated that TGFβ1 induces apoptosis and EMT in prostate cancer cells via activation of P38-MAPK and Rac1/Pak1 respectively. Our results reveal the potential therapeutic benefits of targeting TGFβ1-Pak1 pathway for advanced-stage prostate cancer.

BackgroundRecent studies suggest the potential benefits of statins as anti-cancer agents. Mechanisms by which statins induce apoptosis in cancer cells are not clear. We previously showed that simvastatin inhibit prostate cancer cell functions and tumor growth. Molecular mechanisms by which simvastatin induce apoptosis in prostate cancer cells is not completely understood.MethodsEffect of simvastatin on PC3 cell apoptosis was compared with docetaxel using apoptosis, TUNEL and trypan blue viability assays. Protein expression of major candidates of the intrinsic pathway downstream of simvastatin-mediated Akt inactivation was analyzed. Gene arrays and western analysis of PC3 cells and tumor lysates were performed to identify the candidate genes mediating extrinsic apoptosis pathway by simvastatin.ResultsData indicated that simvastatin inhibited intrinsic cell survival pathway in PC3 cells by enhancing phosphorylation of Bad, reducing the protein expression of Bcl-2, Bcl-xL and cleaved caspases 9/3. Over-expression of PC3 cells with Bcl-2 or DN-caspase 9 did not rescue the simvastatin-induced apoptosis. Simvastatin treatment resulted in increased mRNA and protein expression of molecules such as TNF, Fas-L, Traf1 and cleaved caspase 8, major mediators of intrinsic apoptosis pathway and reduced protein levels of pro-survival genes Lhx4 and Nme5.ConclusionsOur study provides the first report that simvastatin simultaneously modulates intrinsic and extrinsic pathways in the regulation of prostate cancer cell apoptosis in vitro and in vivo, and render reasonable optimism that statins could become an attractive anti-cancer agent.

Vascular permeability regulated by the vascular endothelial growth factor (VEGF) through endothelial-barrier junctions is essential for inflammation. Mechanisms regulating vascular permeability remain elusive. Although ‘Akt’ and ‘Src’ have been implicated in the endothelial-barrier regulation, it is puzzling how both agents that protect and disrupt the endothelial-barrier activate these kinases to reciprocally regulate vascular permeability. To delineate the role of Akt1 in endothelial-barrier regulation, we created endothelial-specific, tamoxifen-inducible Akt1 knockout mice and stable ShRNA-mediated Akt1 knockdown in human microvascular endothelial cells. Akt1 loss leads to decreased basal and angiopoietin1-induced endothelial-barrier resistance, and enhanced VEGF-induced endothelial-barrier breakdown. Endothelial Akt1 deficiency resulted in enhanced VEGF-induced vascular leakage in mice ears, which was rescued upon re-expression with Adeno-myrAkt1. Furthermore, co-treatment with angiopoietin1 reversed VEGF-induced vascular leakage in an Akt1-dependent manner. Mechanistically, our study revealed that while VEGF-induced short-term vascular permeability is independent of Akt1, its recovery is reliant on Akt1 and FoxO-mediated claudin expression. Pharmacological inhibition of FoxO transcription factors rescued the defective endothelial-barrier due to Akt1 deficiency. Here we provide novel insights on the endothelial-barrier protective role of VEGF in the long-term and the importance of Akt1-FoxO signaling on tight-junction stabilization and prevention of vascular leakage through claudin expression.

14-3-3 proteins are ubiquitously expressed dimeric adaptor proteins that have emerged as key mediators of many cell signaling pathways in multiple cell types. Its effects are mainly mediated by binding to selective phosphoserine/threonine proteins. The importance of 14-3-3 proteins in cancer have only started to become apparent and its exact role in cancer progression as well as the mechanisms by which 14-3-3 proteins mediate cancer cell function remain unknown. While protein 14-3-3σ is widely accepted as a tumor suppressor, 14-3-3ζ, β and γ isoforms have been shown to have tumor promoting effects. Despite the importance of 14-3-3 family in mediating various cell processes, the exact role and mechanism of 14-3-3ζ remain unexplored. In the current study, we investigated the role of protein 14-3-3ζ in prostate cancer cell motility and transendothelial migration using biochemical, molecular biology and electric cell-substrate impedance sensing approaches as well as cell based functional assays. Our study indicated that expression with wild-type protein 14-3-3ζ significantly enhanced Rac activity in PC3 cells. In contrast, expression of dimer-resistant mutant of protein 14-3-3ζ (DM-14-3-3) inhibited Rac activity and associated phosphorylation of p21 activated kinase-1 and 2. Expression with wild-type 14-3-3ζ or constitutively active Rac1 enhanced extracellular matrix recognition, lamellipodia formation, cell migration and trans-endothelial migration by PC3 cells. In contrast, expression with DM 14-3-3ζ or DN-Rac1 in PC3 cells significantly inhibited these cell functions. Our results demonstrate for the first time that 14-3-3ζ enhances prostate cancer cell-matrix interactions, motility and transendothelial migration in vitro via activation of Rac1-GTPase and is an important target for therapeutic interventions for prostate cancer.

Background: Due to aging, along with its associated physiological changes, older adults are extremely vulnerable to be afflicted with multiple chronic conditions (multimorbidity). Accordingly, prescribing a large number of drugs to older adults would be inevitable. Resulted complex drug regimens can lead to prescribing of Potentially Inappropriate Medications (PIMs) with subsequent negative health and economic outcomes. Objectives: The main objective of this study is to investigate the prevalence and predictors of PIMs prescribing among Jordanian elderly outpatients, using the last updated version of the American Geriatrics Society (AGS) Beers Criteria (2015 version). Methods: A Unicenter, cross-sectional study were data was assessed using medical records of included study subjects conducted over three months period from beginning of October to the end of December 2016 at King Abdullah University Hospital, Al Ramtha, Jordan. Our study included patients aged 65 years or above who visited the outpatient clinics at King Abdullah University hospital (KAUH) and were prescribed at least one oral medication during the study period. PIMs were identified for these patients and further classified according to the 2015 AGS Beers Criteria. We measured the prevalence of PIMs prescribed among elderly outpatients in Jordan. Results: A total of 4622 eligible older adults were evaluated in this study, of whom 62.5% (n=2891) were found to have at least one PIM prescribed during the three months study period. 69% of identified PIMs were medications to be used with caution in elderly, 22% were medications to avoid in many or most older adults, 6.3% were medications to be avoided or have their dosage adjusted based on kidney function in older adults, 2.04% medications were to avoid in older adults with specific diseases/syndromes, and 1.6% were potentially clinically important non-anti-infective drug-drug interactions to be avoided in older adults. Female gender and polypharmacy were found to be significant predictors of PIMs use among elderly. Conclusions: Potentially Inappropriate Medication prescribing is common among Jordanian elderly outpatients. Female gender and polypharmacy are associated with more PIMs prescribing and so need further attention.

P21 activated kinases-1 (PAK-1)is implicated in various diseases. It is inhibited by thesmall molecule ‘Inhibitor targeting PAK1 activation-3’ (IPA-3), which is highly specific but metabolically unstable. To address this limitation we encapsulatedIPA-3 in sterically stabilized liposomes (SSL). SSL-IPA-3 averaged 139 nm in diameter, polydispersity index (PDI) of 0.05, and a zeta potential of −28.1, neither of which changed over 14 days; however, the PDI increased to 0.139. Analysis of liposomal IPA-3 levels demonstrated good stability, with 70% of IPA-3 remaining after 7 days. SSL-IPA-3 inhibited prostate cancer cell growth in vitro with comparable efficacy to free IPA-3. Excitingly, only a 2 day/week dose of SSL-IPA-3 was needed to inhibit the growth of prostate xenografts in vivo, while a similar dose of free IPA-3 was ineffective. These data demonstrate the development and clinical utility of a novel liposomal formulationfor the treatment of prostate cancer. The small molecule ‘Inhibitor targeting P21-activated kinase-1 (PAK1) activation-3’ (IPA-3) has potential anti-cancer effects, but is metabolically unstable. We encapsulated IPA-3 in sterically stabilized liposomes (SSL) that averaged 139 nm in diameter, polydispersity index (PDI) of 0.05, and a zeta potential of −28.1, which was stable for over 14 days with 70 % of IPA-3 remaining even after 7 days. A 2 day/week administration of 5 mg/Kg dose of SSL-IPA-3 significantly inhibited the growth of prostate xenografts in vivo as compared to similar dose of free IPA-3, demonstrating the potential benefits of SSL-IPA-3 for the management of prostate cancer.