Z, A., and A. H, "Renin–Angiotensin System Implications to COVID‑19 Comorbidities", Journal of microscopy and ultrastructure, vol. 8, issue 4, pp. 148-151, 2020.
Alrefaie, Z., H. Awad, K. Alsolami, and E. A. Hamed, "Uncoupling proteins: are they involved in vitamin D3 protective effect against high-fat diet-induced cardiac apoptosis in rats?", Archives of physiology and biochemistry, pp. 1-9, 2020. Abstract

This study aimed to assess the impact of high-fat diet (HFD) and vitamin D3 supplementation on cardiac apoptosis, inflammation, oxidative stress, and cardiac uncoupling proteins (UCPs) 2&3 expression. Forty rats were fed either (45%) or (10%) fat diet with or without vitamin D3 (500 U/kg/day) for 6 months, then cardiac tissue expression of Bax, Bcl2, Fas, Fas-L (markers for apoptotic pathways), TNF-, MDA7, GPX1 (inflammatory and oxidative markers) and UCP 2&3 were assessed. Results revealed the enhancement of intrinsic and extrinsic cardiomyocyte apoptosis cascades and increased inflammatory and oxidative burdens on the heart in HFD rats. Downregulation of UCP2 and upregulation of UCP3 gene expression at 6 months. After vitamin D3 supplementation with HFD, cardiac apoptotic, inflammatory and oxidative markers were mitigated and expression of UCP3 was downregulated and UCP2 was upregulated. This work highlights the novel cardioprotective effect of vitamin D3 in the experimental model of HFD feeding through the downregulation of UCP3.

Z, A., E. B, and A. N, "Effect of integrating research skills with basic sciences in an interdisciplinary integrated endocrine module on students’ satisfaction and performance", Indian Journal of Pharmaceutical Education and Research , vol. 51, issue 1, pp. 14-19, 2017.
Alrefaie, Z., A. Al-Hayani, M. Hassanien, and A. Hegazy, "Implementing group research assignment in undergraduate medical curriculum; impact on students' performance and satisfaction.", BMC medical education, vol. 20, issue 1, pp. 229, 2020. Abstract

BACKGROUND: Medical educators need to integrate research skills within undergraduate medical curriculum to help students perceive their relevance to routine doctor's practice. The current work aimed to assess the impact of including group research assignment in the endocrine module to third year medical students on attaining some research, communication and E learning skills and on their performance in the module.

METHODS: Students carried out a group research activity (N = 10), wrote a report and presented their work as a poster, booklet or video clip. Multiple evaluation methods were used; a questionnaire to assess students' satisfaction and perception towards the skills acquired and a rubric to grade the research report and presentation. Also, students' final grades in the module were compared with that of the previous cohort who didn't conduct the research assignment.

RESULTS: Students' response rate to the questionnaire was 50%. 73.6% of students agreed that research enhanced critical evaluation of literature while 65.5% felt confident to further participate in research and 66.7% were satisfied about the whole research experience. Mean score of assignment was 84% for female students and 78% for male students. Grades of the current cohort in the endocrine module were significantly higher than that of the preceding cohort (78.7 ± 11 and 70.2 ± 13 respectively P< 0.001).

CONCLUSION: The current study pointed to the positive impact of implementing group research assignment within the undergraduate medical curriculum. Students were satisfied about the research exposure, agreed attaining some skills and got higher grades than preceding peers.

Alrefaie, Z., and I. Moustafa, "Vitamin D3 favorable outcome on recognition memory and prefrontal cortex expression of choline acetyltransferase and acetylcholinesterase in experimental model of chronic high-fat feeding.", The International journal of neuroscience, vol. 130, issue 3, pp. 262-269, 2020. Abstract

High-fat diet (HFD) consumption and insufficient vitamin D levels are globally increasing phenomena. The present study assessed the effect of chronic HFD feeding with and without vitamin D supplementation on recognition memory and prefrontal cortex expression of choline acetyltransferase (CAT) and acetylcholinesterase (Achase). Forty male Wistar rats were subjected to four dietary regimens ( = 10); control diet (10% fat), control + vitamin D3, high-fat diet (HFD 45% fat) and HFD + vitamin D3 for 6 months. Rats were tested for the novel object recognition test, and their prefrontal cortices were assessed for expression of CAT and Achase. Recognition memory was impaired in HFD-fed rats compared to control rats as evidenced by significantly decreased discrimination index in the novel object recognition test. Moreover, CAT expression was significantly decreased while Achase expression was significantly increased in the prefrontal cortex of HFD-fed rats. Vitamin D3 supplementation with HFD significantly increased the exploration of the novel object and the discrimination index and attenuated the alterations in the prefrontal cortex CAT and Achase expression. The present findings support the potential effect of vitamin D on recognition memory and cholinergic transmission in the prefrontal cortex and add to the pathophysiology of HFD consumption.

Alrefaie, Z., and H. Awad, "Effect of vitamin D3 on thyroid function and de-iodinase 2 expression in diabetic rats.", Archives of physiology and biochemistry, vol. 121, issue 5, pp. 206-9, 2015. Abstract

OBJECTIVE: This study aimed to assess the effect of vitamin D3 administration to diabetic rats on thyroid profile and deiodinase 2 (D2).

METHODS: Thirty male Wistar rats were included into three groups; control, streptozotocin-induced diabetic and diabetic supplemented with vitamin D3 groups. Ten weeks later, serum levels of free T4, free T3 and TSH were measured. Tissue homogenates from liver, kidney, muscle, femur bone, heart and brain were obtained and assessed for D2 mRNA.

RESULTS: Diabetic rats demonstrated significant increase in free T4 and significant decrease in free T3. These changes were ameliorated by vitamin D3 administration. D2 mRNA was significantly reduced in all tissue homogenates obtained from diabetic rats, while vitamin D3 treatment significantly enhanced D2 in liver and brain homogenates.

CONCLUSION: Diabetes mellitus inhibited peripheral conversion of T4 into T3 secondary to reduction in D2 expression. Vitamin D3 greatly corrected the alterations in thyroid profile and D2 expression.

Alrefaie, Z., "Grape Seed Proanthocyanidins Attentuate Anxiety-Like Behavior in an Experimental Model of Dietary-Induced Hypercholesterolemia in Rats.", International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition, pp. 1-10, 2016 Jul 14. Abstract

OBJECTIVE: Grape seed proanthocyanidins have many health-protective effects. The present work aimed to assess their possible anxiolytic effects in dietary-induced hy-percholesterolemia in rats.

METHODS: 30 Male Wistar rats were divided into 3 groups (n = 10): control (normal chow), high cholesterol (cholesterol and cholic acid chow) and high cholesterol + grape seed extract (hypercholesterolemic chow + grape seed extract, 100 mg/kg body weight/day). After 4 months, total cholesterol levels and animals' behavior in the open field and elevated plus maze were assessed.

RESULTS: High-cholesterol diet elevated cholesterol levels (p < 0.001 vs control group), however, grape seed administration ameliorated this elevation (p < 0.001 vs high-cholesterol un-treated group). In the open field, hypercholesterolemic rats showed increased periods of immobility (138 ± 20.3 seconds (s) vs 96.9 ± 14.5 in control rats p < 0.001) and time latency to enter field center (109 ± 18.3 s compared to 40.8 ± 10.5 s in the control group p < 0.001). Both parameters were reduced by grape seed treatment (p < 0.01, p < 0.001 vs the untreated hypercholesterolemic group, respectively). Elevated plus maze testing demonstrated higher closed-arm entries (5.5 ± 1.1 in hypercholesterolemic an-imals vs 3 ± 1.1 in the control group p < 0.001) and lower percentage of time spent in open arms (19.7 ± 3.5 % vs 35.8 ± 4.8 % in control rats p < 0.001). Grape seed extract significantly enhanced the percentage of time spent in open arms (p < 0.001 compared to hypercholesterolemic rats).

CONCLUSION: The present results highlight the possible anxiolytic effect of grape seed proanthocyanidins in dietary-induced hypercholester-olemia.

Alrefaie, Z. A., H. A. Amin, and S. H. Elgayed, "Estrogenicity of outer scales of onion on uteri of immature mice.", Canadian journal of physiology and pharmacology, 2011 Nov 1. Abstract

We aimed to investigate the estrogen-like activities of the outer scales of onion and garlic on the uteri of immature mice. This work compared the estrogenic effects induced by estradiol with the effects of plant extract (onion, garlic) in models of immature mice (n = 72). The animals were divided into 6 groups, with 12 animals in each group, as follows: Group I (control group), Group II (estradiol-treated group), Group III (onion extract treated group), Group IV (onion extract treated group after blockage of estrogen receptors), Group V (garlic extract treated group), and Group VI (garlic extract treated group after blockage of estrogen receptors). Uterine wet weight/body mass ratios were determined. Uterotrophic bioassay, immunohistochemical assay for estrogen receptor and proliferative marker Ki67, uterine contractility, and serum estrogen levels were investigated. Onion extract induced proliferative changes in the uterus, it also increased the uterine mass and epithelial cell height. Also, the frequency and amplitude of myometrial contractility were significantly increased in the group treated with onion extract. This estrogenic activity could be attributed to the quercetin and daidzein content, and activation of estrogenic receptors, as these effects disappeared after blockage of E2 receptors. Our results support the possible estrogenic properties of the onion extract, which could be attributed to quercetin and daidzein, but not that of garlic extract.

Alrefaie, Z., "Brief assessment of supine heart rate variability in normal weight, overweight, and obese females.", Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc, vol. 19, issue 3, pp. 241-6, 2014 May. Abstract

BACKGROUND: Little research has been conducted on the heart rate variability (HRV) parameters in late adolescent females. The present study aimed to assess HRV time and frequency domain parameters in overweight and obese late adolescent females. Also to assess any possible correlation between HRV parameters and obesity indices in that particular age group.

SUBJECTS AND METHODS: Fifteen-minute period of standardized ECG recording was implemented to record HRV time and frequency parameters in 42 normotensive euglycemic female medical students aged (18-21 years); lean (n = 13), overweight (n = 13), and obese (n = 16). For the analysis of results, 2.5-minute data were used.

RESULTS: Root mean squares of successive differences between adjacent RR intervals (rMSSD) and high-frequency (HF) power were significantly decreased in overweight and obese late adolescent females. Parameters reflecting sympathetic activity which include low-frequency (LF) power and LF/HF ratio showed significant increase in overweight group. Interestingly, LF power was significantly reduced in obese group while the LF/HF ratio was insignificantly different. No significant correlations were observed between HRV indices and parameters of total or visceral obesity in the study groups.

CONCLUSION: HRV indices showed sympathetic hyperactivity in overweight late adolescent females and diminished sympathetic response in matching obese group. Both overweight and obese females showed decreased protective vagal influence on the heart.

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