Comparison between the Regenerative and Therapeutic Impacts of Bone Marrow Mesenchymal Stem Cells and Adipose Mesenchymal Stem Cells Pre-Treated with Melatonin on Liver Fibrosis.

BACKGROUND: The distinctive feature of liver fibrosis is the progressive replacement of healthy hepatic cells by the extracellular matrix protein, which is abundant in collagen I and III, with impaired matrix remodeling. The activation of myofibroblastic cells enhances the fibrogenic response of complex interactions of hepatic stellate cells, fibroblasts, and inflammatory cells to produce the excessive deposition of the extracellular protein matrix. This process is activated by multiple fibrogenic mediators and cytokines, such as TNF-α and IL-1ß, accompanied with a decrease in the anti-fibrogenic factor NF-κß. Mesenchymal stem cells (MSCs) represent a promising therapy for liver fibrosis, allowing for a more advanced regenerative influence when cultured with extrinsic or intrinsic proliferative factors, cytokines, antioxidants, growth factors, and hormones such as melatonin (MT). However, previous studies showed conflicting findings concerning the therapeutic effects of adipose (AD) and bone marrow (BM) MSCs; therefore, the present work aimed to conduct a comparative and comprehensive study investigating the impact of MT pre-treatment on the immunomodulatory, anti-inflammatory, and anti-apoptotic effects of AD- and BM-MSCs and to critically analyze whether MT-pre-treated AD-MSCs and BM-MSCs reveal equal or different therapeutic and regenerative potentials in a CCl4-injured liver experimental rat model. MATERIALS AND METHODS: Six groups of experimental rats were used, with ten rats in each group: group I (control group), group II (CCl4-treated group), group III (CCl4- and BM-MSC-treated group), group IV (CCl4 and MT-pre-treated BM-MSC group), group V (CCl4- and AD-MSC-treated group), and group VI (CCl4 and MT-pre-treated AD-MSC group). Liver function tests and the gene expression of inflammatory, fibrogenic, apoptotic, and proliferative factors were analyzed. Histological and immunohistochemical changes were assessed. RESULTS: The present study compared the ability of AD- and BM-MSCs, with and without MT pre-treatment, to reduce hepatic fibrosis. Both types of MSCs improved hepatocyte function by reducing the serum levels of ALT, aspartate aminotransferase (AST), alkaline phosphatase (AKP), and total bilirubin (TBIL). In addition, the changes in the hepatocellular architecture, including the hepatocytes, liver sinusoids, central veins, portal veins, biliary ducts, and hepatic arteries, showed a decrease in hepatocyte injury and cholestasis with a reduction in inflammation, apoptosis, and necrosis of the hepatic cells, together with an inhibition of liver tissue fibrosis. These results were augmented by an analysis of the expression of the pro-inflammatory cytokines TNFα and IL-1ß, the anti-fibrogenic factor NF-κß, the apoptotic factor caspase-3, and the proliferative indicators antigen Ki-67 and proliferating cell nuclear antigen (PCNA). These findings were found to be statistically significant, with the restoration of normal parameters in the rats that received AD-MSCs pre-treated with MT, denoting optimal regenerative and therapeutic effects. CONCLUSIONS: AD-MSCs pre-treated with MT are the preferred choice in improving hepatic fibrosis and promoting the therapeutic and regenerative ability of liver tissue. They represent a very significant tool for future stem cell use in the tissue regeneration strategy for the treatment of liver diseases.

Medical imaging in problem-based learning and impact on the students: A cross-sectional study.

OBJECTIVE: To investigate the medical students' performance with and perception towards different multimedia medical imaging tools. METHODS: The cross-sectional study was conducted at the College of Medicine, Qassim University, Saudi Arabia, from 2019 to 2020, and comprised third year undergraduate medical students during the academic year 2019-2020. The students were divided into tow groups. Those receiving multimedia-enhanced problem-based learning sessions were in intervention group A, while those receiving traditional problem-based learning sessions were in control group B. Scores of the students in the formative assessment at the end of the sessions were compared between the groups. Students' satisfaction survey was also conducted online and analysed. Data was analysed using SPSS 21. RESULTS: Of the 130 medical students, 75(57.7%) were males and 55(42.3%) were females. A significant increase in the mean scores was observed for both male and female students in group A compared to those in group B (p<0.05). The perception survey was filled up by 100(77%) students, and open-ended comments were obtained from 88(88%) of them. Overall, 69(74%) subjects expressed satisfaction with the multimedia-enhanced problem-based learning sessions. CONCLUSIONS: Radiological and pathological images enhanced the students' understanding, interaction and critical thinking during problem-based learning sessions.

The impact of flipped classroom: Evaluation of cognitive level and attitude of undergraduate medical students.

BACKGROUND: Anatomy is a core component of the basic health sciences and a structural foundation for higher clinical courses. Mastering this foundational science is an essential competency for health care providers. Some medical schools still adopt the traditional teacher-centered methods for teaching anatomy with the disadvantages of lacking the students' opportunity to practice higher levels of thinking such as application, interpretation, or analysis during class. One of the promising teaching strategies that enhance student engagement is the flipped classroom (FC). The present study explored the students' achievement during the anatomy FC, compared with traditional classroom for the first time in Qassim College of Medicine. METHODS: Online educational materials were uploaded on the Blackboard in the form of electronic textbooks, PowerPoint presentations, online websites, journal articles and multimedia in the pre-class phase of the FC. The in-class phase included open discussion and problem-solving activities were based upon the digitalized resources. Students' attendance was recorded during the in-class sessions. Comparison between the students' scores of the pre-and post-tests for both the FC and traditional classroom. A computed students' survey towards the FC was analysed. RESULTS: The mean students' scores of the lower and higher-order thinking questions of the FC in the pre-tests were significantly increased in the pre-tests (4.40 ± 1.18 and 1.39 ± 0.53 respectively), compared with that of the traditional classroom (1.44 ± 1.09 and 0.41 ± 0.51 respectively) as well as in the post-tests (5.73 ± 1.03 and 2.14 ± 0.71), compared with that of the traditional classroom (5.07 ± 1.2 and 1.66 ± 0.93 respectively). The absence rate of the students during the FC was lower by 16.13%. Students' survey conveyed their satisfaction towards the FC. Cronbach's alpha test revealed high reliability of all students' survey items and their correlation coefficient was positive. CONCLUSION: The current work concluded that the educational outcome gained from the technology-enhanced active learning (TEAL), through the implementation of the anatomy FC, enhanced the students' achievement and commitment and suggested the upgrading of the anatomy teaching methods and exploring the long-term effects of the FC.

Impact of platelet-rich plasma versus selenium in ameliorating induced toxicity in rat testis: histological, immunohistochemical, and molecular study.

This study was conducted on forty adult rats divided into four groups: Group I (control) that is divided into subgroups A, B, and C and Group II (methotrexate (MTX)-treated); the rats were injected intraperitoneally with MTX at a dose of 1 mg/kg/week, for 8 weeks. Group III (MTX-Se co-treated) was injected with MTX like Group II plus an oral administration of selenium at a dose of 10 µg/kg b.w/day, for 8 weeks. Group IV (MTX-PRP co-treated), rats were injected intraperitoneally with MTX like Group II plus platelet-rich plasma (PRP) injection under the scrotum, three times with 2-week intervals (volume-0.1 ml per injection) and euthanized after 8 weeks. Histological, immunohistochemical, and genetic expression using qPCR and western blotting technique were conducted. There was improvement in histological structure of testes in most specimens of Group IV. The latter group revealed a significant decrease in Bax and an increase in Bcl-2. The regeneration of testicular tissue was more observed in Group IV as measured by an increase in mean number of PCNA. Moreover, Group IV revealed an increased genetic level of FSCN3, GCNF, UBQLN3, and DAZL. Both MTX-Se and MTX-PRP have an anti-inflammatory effect as measured by a reduction in NF-κb. The anti-oxidative effect of selenium and PRP was noticed by a decrease in the level of the iNos and an increase in eNos protein and the autophagy marker LC3. PRP has ameliorative effects on induced rat testicular toxicity as evaluated by morphological changes and confirmed by immunohistochemical reactions, genetic expression, and western blotting analyses including oxidative and anti- oxidative markers.

Experience of e-learning and online assessment during the COVID-19 pandemic at the College of Medicine, Qassim University.

OBJECTIVES: During the COVID-19 pandemic, academic institutions are promptly shifting all educational activities to the e-learning format. The present work describes concurrent procedures for online teaching and assessment performed at the College of Medicine, Qassim University, KSA. We also explored the impact of e-learning and assessment on the performance of students and faculty, and the challenges to their sustainability. METHODS: In this descriptive cross-sectional study, we recorded the number and duration of different online educational activities during the COVID-19 pandemic. Training sessions for various procedures of virtual classrooms and online assessments were organised for teachers and students. A newly established e-assessment committee arranged different online assessments. A comparison between the mean problem-based learning (PBL) grades of the same students was conducted either face-to-face or online. A student satisfaction survey and online staff focus group about the online learning experiences were conducted, and weekly staff perception reports were prepared. The results obtained were then analysed. RESULTS: A total of 620 virtual classrooms were successfully implemented over 994 h including theoretical lectures, PBL sessions, seminars, and tutorials. A significant increase in the mean PBL grades was observed for female students during the online sessions. Out of the basic year students and staff, 58.82% reflected their high satisfaction towards virtual classrooms, online assessment, and online workshops. CONCLUSION: The present study elaborates on the benefits of e-learning and assessment. We observed higher student achievements and promising staff perceptions with obvious improvement in their technological skills. These findings support the shift towards future implementation of more online medical courses.

Digitalization plan in medical education during COVID-19 lockdown.

BACKGROUND: The COVID-19 pandemic has enhanced the adoption of virtual learning after the urgent suspension of traditional teaching. Different online learning strategies were established to face this learning crisis. The present descriptive cross-sectional study was conducted to reveal the different digital procedures implemented by the College of Medicine at Qassim University for better student performance and achievement. METHODS: The switch into distance-based learning was managed by the digitalization committee. Multiple online workshops were conducted to the staff and students about the value and procedures of such a shift. New procedures for online problem-based learning (PBL) sessions were designed. Students' satisfaction was recorded regarding the efficiency of live streaming educational activities and online assessment. RESULTS: The students were satisfied with the overall shift into this collaborative e-learning environment and the new successful procedures of virtual PBL sessions. The digital learning tools facilitated the performance of the students and their peer sharing of knowledge. The role of informatics computer technologies was evident in promoting the students, research skills, and technical competencies. CONCLUSIONS: The present work elaborated on the procedures and privileges of the transformation into digitalized learning, particularly the PBL sessions, which were appreciated by the students and staff. It recommended the adoption of future online theoretical courses as well as the development of informatics computer technologies.

The protective effect of 1alpha, 25-dihydroxyvitamin d3 and metformin on liver in type 2 diabetic rats.

There is an accumulating evidence suggesting an immunomodulatory role of 1α,25(OH)2D3. Altered 1α,25(OH)2D3 level may play a role in the development of T2DM and contribute to the pathogenesis of liver diseases. Our study was designed to study and compare the effect of metformin and 1α,25(OH)2D3 supplementation on liver injury in type 2 diabetic rat. Sixty male Albino rats were divided into 5 groups; group 1: control rats. the remaining rats were fed high fat diet for 2 weeks and injected with streptozotocin (35mg/kg BW, i.p.) to induce T2DM and were divided into: group 2: untreated diabetic rats, group 3: diabetic rats treated by metformin (100mg/kgBW/d, orally), group 4: diabetic rats supplemented by 1α,25(OH)2D3 (0.5µg/kg BW, i.p.) 3 times weekly and group 5: supplemented by both 1α,25(OH)2D3 and metformin. Eight weeks later, serum glucose and insulin levels were measured, HOMA IR was calculated, lipid profile, Ca2+, ALT and AST were estimated. Liver specimens were taken to investigate PPAR-α (regulator of lipid metabolism), NF-κB p65, caspase 3 and PCNA (proliferating cell nuclear antigen) and for histological examination. The liver enzymes were elevated in the diabetic rats and the histological results revealed an injurious effect of diabetes on the liver. 1α,25(OH)2D3, metformin and both drugs treatment significantly improved liver enzymes as compared to the untreated rats. The improvement was associated with a significant improvement in the glycemic control, lipid profile and serum Ca2+ with a significant reduction in NF-κB p65 and caspase 3 and increased PPAR-α, and PCNA expression as compared to the untreated group. 1α,25(OH)2D3 induced a slightly better effect as compared to metformin. Both agents together had a synergistic action and almost completely protected the liver. Histological results confirmed the biochemical findings. Our results showed a protective effect of 1α,25(OH)2D3 and metformin on liver in diabetic rats as indicated by an improvement of the level of the liver enzymes, decreased apoptosis and increased proliferation and this was confirmed histologically, with modulating NFkB and PPAR-α. Both agents together had a synergistic effect.