Amin, S. N., F. Asali, M. F. M. Elrefai, W. B. E. Gazzar, S. A. Shaltout, D. A. Elberry, S. S. Kamar, N. S. A. Latif, M. N. Mehesen, M. M. Ayoub, et al., "Insight Towards Induction of Reproductive-Metabolic Phenotypes of Polycystic Ovarian Syndrome", Jordan Journal of Biological Sciences, vol. 15, issue 5, pp. 813 – 824, 2022. paper_number_10.pdf
Tawfik, D. I., D. M. Elkhashab, R. K. A. Elnour, N. M. Kamal, O. A. Khorshid, and M. N. Mehesen, "Possible renoprotective effect of valsartan/sacubitril versus valsartan and Metformin in rat model of diabetic nephropathy", Journal of Advanced Pharmacy Education & Research, vol. 13, issue (1), pp. 51-61, 2023. japer-vol-13-iss-1-51-61-8077_1.pdf
Hassan, F. E. S., B. E. Aboulhoda, M. N. Mehesen, P. M. El Din, H. A. Abdallah, E. R. Bendas, L. A. Rashed, A. Mostafa, M. F. Amer, M. Abdel-Rahman, et al., "Combination therapy of systemic and local metformin improves imiquimod-induced psoriasis-like lesions with type 2 diabetes: the role of AMPK/KGF/STAT3 axis.", Archives of physiology and biochemistry, pp. 1-13, 2024. Abstract

CONTEXT: Insulin resistance and a disturbed lipid profile are common associations with type 2 diabetes mellitus (T2DM) and different skin diseases, particularly psoriasis (PsO).

OBJECTIVES: We investigated potential therapeutic mechanisms of metformin in a murine animal model of psoriasiform lesions in T2DM.

MATERIALS AND METHODS: Forty-two rats were randomly divided into control, PsO, and type II DM (T2DM) groups. After confirmation of DM, the type II diabetic rats were allocated into T2DM+ PsO, T2DM+ PsO+ systemic metformin (S. met), T2DM+ PsO+ topical metformin (T. met)), and T2DM+ PsO + combined metformin (C. met). PsO was induced by topical imiquimod.

RESULTS: Systemic administration of the cornerstone antidiabetic drug, metformin, was able to improve insulin resistance and lipid profile. At molecular levels, both topical and systemic metformin significantly increased AMP-activated protein kinase (AMPK), and lowered keratinocyte growth factor (KGF) / "Signal transducer and activator of transcription" (STAT)3 protein levels, and the IL-17RA and IL-17RC gene expression.

CONCLUSION: Although its glucose-controlling effect was not optimum, T.met gel served anti-psoriatic and anti-inflammatory effects.

Amin, S. N., F. Asali, I. Aolymat, D. Abuquteish, O. Abu Al Karsaneh, W. B. E. Gazzar, S. A. Shaltout, Y. J. Alabdallat, D. A. Elberry, S. S. Kamar, et al., "Comparing MitoQ10 and heat therapy: Evaluating mechanisms and therapeutic potential for polycystic ovary syndrome induced by circadian rhythm disruption.", Chronobiology international, vol. 40, issue 8, pp. 1004-1027, 2023. Abstract

Environmental factors, such as sleep restriction, contribute to polycystic ovary syndrome (PCOS) by causing hyperinsulinemia, hyperandrogenism, insulin resistance, and oligo- or anovulation. This study aimed to evaluate the effects of circadian rhythm disruption on reproductive and metabolic functions and investigate the potential therapeutic benefits of MitoQ10 and hot tub therapy (HTT). Sixty female rats were divided into six groups: control, MitoQ10, HTT, and three groups with PCOS induced by continuous light exposure(L/L). The reproductive, endocrine, and structural manifestations ofL/L-induced PCOS were confirmed by serum biochemical measurements, ultrasound evaluation of ovarian size, and vaginal smear examination at week 14. Subsequently, the rats were divided into the L/L (untreated), L/L+MitoQ10-treated, andL/L+HTT-treated groups. At the end of week 22, all rats were sacrificed. Treatmentwith MitoQ10 or HTT partially reversed the reproductive, endocrine, and structural features of PCOS, leading to a decreased amplitude of isolated uterine contractions, ovarian cystic changes and size, and endometrial thickness. Furthermore, both interventions improved the elevated serum levels of anti-Mullerian hormone (AMH), kisspeptin, Fibulin-1, A disintegrin and metalloproteinase with thrombospondin motifs 19 (ADAMTS-19), lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR), oxidative stress markers, androgen receptors (AR) and their transcription target genes, FKBP52 immunostaining in ovarian tissues, and uterine estrogen receptor alpha (ER-α) and PRimmunostaining. In conclusion, MitoQ10 supplementation and HTT demonstrated the potential for ameliorating metabolic, reproductive, and structural perturbations associated with PCOS induced by circadian rhythm disruption. These findings suggest a potential therapeutic role for these interventions in managing PCOS in women.

Shamseldeen, A. M., S. A. A. El-Aal, B. E. Aboulhoda, H. AbdAllah, S. M. Gamal, F. E. Hassan, M. N. Mehesen, L. A. Rashed, A. Mostafa, and N. B. Sadek, "Combined Systemic Intake of K-ATP Opener (Nicorandil) and Mesenchymal Stem Cells Preconditioned With Nicorandil Alleviates Pancreatic Insufficiency in a Model of Bilateral Renal Ischemia/Reperfusion Injury.", Frontiers in physiology, vol. 13, pp. 934597, 2022. Abstract

We used nicorandil, a K-ATP channel opener, to study the role of these channels in the amelioration of renal ischemia/reperfusion (I/R)-induced pancreatic injury, and the possible involvement of PI3K/Akt/mTOR signaling pathway. Forty-two male Wistar rats were included in this study, six were sacrificed for extraction of bone marrow mesenchymal stem cells (BM-MSCs) and conducting the work, the others were included study and equally divided into six groups. Group 1 (sham control), but groups 2-6 were subjected to bilateral renal I/R: Group 2 (I/R); Group 3 (I/R-NC), treated with nicorandil; Group 4 (I/R-MSCs), treated with BM-MSCs; Group 5 (I/R-MSCC), treated with nicorandil-preconditioned BM-MSCs; Group 6 (I/R-NC-MSCC), treated with both systemic nicorandil and preconditioned BM-MSCC. Renal injury and subsequent pancreatic damage were detected in the I/R group by a significant increase in serum urea, creatinine, fasting glucose, and pancreatic enzymes. The pancreatic tissues showed a reduction in cellularity and a significant decrease in the expression of the cell survival pathway, PI3K/Akt/mTOR, in the I/R group compared to the control. Preconditioning MSCs with nicorandil significantly enhanced the proliferation assay and decreased their apoptotic markers. Indeed, combined systemic nicorandil and nicorandil-preconditioning maintained survival of MSC in the pancreatic tissue and amelioration of apoptotic markers and pancreatic TNF-α production. Histologically, all treated groups revealed better pancreatic architecture, and increased area % of anti-insulin antibody and CD31, which were all best observed in the NC-MSCC group. Thus, using K-ATP channel opener was efficient to enhance PI3K/Akt/mTOR expression levels ( and ).

Ashour, H., S. M. Gamal, N. B. Sadek, L. A. Rashed, R. E. Hussein, S. S. Kamar, H. Ateyya, M. N. Mehesen, and A. M. Shamseldeen, "Vitamin D Supplementation Improves Uterine Receptivity in a Rat Model of Vitamin D Deficiency: A Possible Role of HOXA-10/FKBP52 Axis.", Frontiers in physiology, vol. 12, pp. 744548, 2021. Abstract

Synchronized uterine receptivity with the time of implantation is crucial for pregnancy continuity. Vitamin D (VD) deficiency has been linked to the failure of implantation. Therefore, we tested the link between the Homeobox transcription factor-10/immunophilin FK506-binding protein 52 (HOXA-10/FKBP52) axis and the uterine receptivity in VD-deficient rats. The effect of VD supplementation at different doses was also investigated. Forty-eight pregnant rats were divided into six groups (eight/group); normal control rats fed with standard chow (control), control rats supplemented with VD (equivalent dose of 400 IU/day) (control-D400). VD-deficient group (DEF) and the three VD deficiency groups with VD supplementation were equivalent to 400, 4,000, and 10,000 IU/day (DEF-D400, DEF-D4000, and DEF-D10000, respectively). The expression levels of HOXA-10/FKBP52, progesterone level, and histological evaluation of decidualization using osteopontin (OSN) and progesterone receptor (PGR) were estimated. An assessment of the uterine contractility was conducted for all rats. This study showed the downregulation of HOXA-10/FKBP52 together with increased amplitude and frequency of the uterine contractility in the DEF group compared to control. VD dose-dependent supplementation restored progesterone/receptor competency, upregulated the expressional response of HOXA-10 and its downstream FKBP52, and improved uterine receptivity and endometrial decidualization at the time of implantation that was documented by increased area% of OSN and the number of implantation beads.

Shams Eldeen, A. M., M. N. Mehesen, B. E. Aboulhoda, L. A. Rashed, M. M. Elsebaie, E. A. Mohamed, and M. M. Gamal, "Prenatal intake of omega-3 promotes Wnt/β-catenin signaling pathway, and preserves integrity of the blood-brain barrier in preeclamptic rats.", Physiological reports, vol. 9, issue 12, pp. e14925, 2021. Abstract

BACKGROUND: Preeclampsia is a systemic, multi-organ endotheliopathy, associated with oxidative injury to the blood-brain barrier (BBB). Preeclampsia initiates a cascade of events that include neuroinflammation. Recently, it was documented that Wnt/β-catenin signaling pathway exerts neuroprotective effects and maintain BBB integrity. We investigate the protective effect of omega-3 against neurovascular complication of preeclampsia and its relation to Wnt/β-catenin signaling pathway.

METHODOLOGY: After confirmation of day 0 pregnancy (G0), 24 adult pregnant female Wistar rats were divided into four groups control pregnant, pregnant supplemented with omega-3, preeclampsia (PE); female rats received N (ω)-nitro-L-arginine methyl ester (L-NAME) (50 mg/kg/day SC from day 7 to day 16 of pregnancy for induction of preeclampsia) and PE rats supplemented with omega-3. The intake of omega-3 started on day zero (0) of pregnancy until the end of the study (144 mg/kg\day orally).

RESULTS: We found that omega-3 supplementation significantly improved cognitive functions and EEG amplitude, decreased blood pressure, water contents of brain tissues, sFlt-1, oxidative stress, proteinuria, and enhanced Wnt\β-catenin proteins. Histological examination showed improved cerebral microangiopathy, increased expression of claudin-1 and -3, CD31, and VEGF in the cerebral cortical microvasculature and choroid plexus in PE rats treated with omega-3. A positive correlation between protein expression level of Wnt \β-catenin and cognitive functions, and a negative correlation between claudin-5 relative expression, claudin-1 and -3 area % from one side and water content of the brain tissues from the other side were observed.

CONCLUSION: Wnt/β-catenin signaling pathway suspected to have an important role to improve BBB integrity. Neuroprotective, antioxidant, and anti-inflammatory effects of omega-3 were observed and can be suggested as protective supplementation for preeclampsia.

El-sayed, L. A., eman osama, M. N. Mehesen, L. A. Rashed, A. G. Aboulkhair, A. I. Omar, and A. M. Shamseldeen, "Contribution of angiotensin II in hepatic ischemia /reperfusion induced lung injury: Acute versus chronic usage of captopril.", Pulmonary pharmacology & therapeutics, vol. 60, pp. 101888, 2020. Abstract

BACKGROUND: Acute lung injury is one of the most popular consequences of hepatic ischemia/reperfusion (I/R) injury. Recently it was documented that renin-angiotensin system plays a key role in tissue inflammation, generation of reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-α) (the principal liver injury mediators) during I/R.

MATERIAL AND METHODS: We investigated the effect of acute versus chronic usage of angiotensin converting enzyme inhibitor (captopril) on liver inflammation and lung injury caused by hepatic ischemia for 1h followed by 24h reperfusion. Forty adult Wistar male rats were divided into sham, I/R, I/R-acute captopril (100 mg/kg, 24 and 1.5 h before surgery) and I/R-chronic captopril (10 mg/kg/day for 28 days before surgery) groups.

RESULTS: We found captopril pretreatment significantly decreased liver damage indices, adhesion molecules, and TNF-α level in hepatic and tracheal tissues. Histologically, acute captopril pretreatment significantly decreased hepatic Kupffer cells number and lung α-smooth muscle actin expression more than chronic pretreatment. Increased tracheal tone, in response to acetylcholine, was suppressed by acute and chronic captopril pretreatment.

CONCLUSION: Angiotensin II plays a key role in tissue inflammation and airway hyperresponsiveness (AHR) via enhancing production of TNF-α. With more protection observed in lung, acute captopril could attenuate liver-induced lung injury via lowering TNF-α; a suggested possible mediator of airway hyperreactivity.

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