One of the major consequences of diabetes mellitus that has gained attention due to its rising incidence is cognitive impairment. Recent research suggested that sodium-glucose cotransporter-2 (SGLT-2) inhibitors can mitigate memory impairment linked to Alzheimer’s disease and are now being explored for their cognitive benefits. However, their mechanisms were not thoroughly studied. This research investigates the hypothesis of the neuroprotective effect of empagliflozin administration against scopolamine-heavy metal mixture (SCO + HMM)-treated Alzheimer’s rat models in comparison with memantine as a reference drug and the impact of their combination. Yet, the neuroprotective effects of memantine and empagliflozin combination against cognitive impairment have not been previously explored. This study employed adult male albino rats categorized into five groups. The impact of empagliflozin, memantine, and their concomitant administration on cognitive performance was assessed in a scopolamine and heavy metal mixture-treated Alzheimer’s disease model in rats. The assessment of rats’ cognitive behavior, memory, and spatial learning was conducted, followed by an evaluation of hippocampal brain-derived neurotrophic factor (BDNF), beta-secretase (BACE-1), oxidative stress (OS), and inflammatory marker activity. And, a western blot analysis was conducted to detect phosphorylated 5’ AMP-activated protein kinase (p-AMPK), phosphorylated mammalian target of rapamycin (p-mTOR), and heme oxygenase-1 (HO-1). Hippocampal and cerebellar histopathology were thoroughly examined, in addition to the expressions of amyloid β (Aβ). The current data demonstrate the involvement of the pAMPK/mTOR/HO-1 signaling pathway in empagliflozin neuroprotection against SCO + HMM-induced AD. In addition, it reduces AD hallmarks (Aβ and BACE1), neuro-inflammation, and oxidative stress sequelae, and enhances neurogenesis and synaptic density via BDNF. This study proposes that EMPA, especially when co-administered with other conventional anti-Alzheimer therapy, may be formulated into an innovative therapeutic strategy for the enhancement of cognitive impairments associated with neurodegenerative disorders.

Juvenile intestinal ischemia–reperfusion (JII/R) is a pediatric surgical emergency caused by mesenteric vessel occlusion and has a high mortality rate. Malrotation can cause intestinal ischemia in infants due to midgut volvulus. It affects not only the intestine itself but also other organs, such as cardiac tissue. Therefore, searching for more effective therapeutic solutions is an essential critical need. This directed our thoughts to evaluate the role of ambrisentan (AMB) in a rat model of induced JII/R by clamping the superior mesenteric artery. Forty juvenile male Wistar albino rats (3–4 weeks old) were randomly divided into four experimental groups: control (CON) group, JII/R group, and AMB-treated groups (30, 60 mg/kg) with JII/R. Induction of JII/R results in significant changes in cardiac enzymes, oxidative stress, inflammatory, and apoptotic parameters with high expression of endothelin receptor A (ERA). Also, histopathological changes revealed extensive mucosal damage, loss of intestinal villi, dysregulated and degenerated cardiac fibers with inflammatory cell infiltration, and tissue necrosis. In contrast, AMB administration significantly reduced the elevated levels of cardiac enzymes, malondialdehyde (MDA), nuclear factor kappa B (NF-κB), ERA, and caspase-3 expression. However, AMB treatment increased immune expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), Ki-67, and mammalian target of rapamycin (mTOR) and showed remarkable improvement in the histopathological changes. AMB could be considered as an adjuvant medical treatment for cases of JII/R.

Background: Anorectal malformations (ARMs) are congenital anomalies that affect the developing hindgut. Sacral development can be used as a prognostic factor in these patients because it parallels the development of the muscles and nerves of the perineum. This study aimed to evaluate the validity of using sacral ratio (SR) and sacral curvature (SC) as predictors for the type of ARMs. Methods: A prospective radiological observational study was conducted on 23 newborns with ARMs at Aswan University Hospitals. ARMs were classified according to the Wingspread classification into low, intermediate, and high. Sacral SR was measured in anteroposterior (AP) and lateral views and SC was measured in lateral view. Both were correlated with ARMs type. Results: High-type ARMs represented 47.8%, low and intermediate were 39.1% and 13%, respectively. Perineal fistula was the most common anomaly (30.4%). SR in both AP and lateral views was significantly lower in the high ARMs group compared to other groups ( p < 0.001). SC showed a lower mean in high ARMs but without statistically significant difference ( p = 0.115). Conclusions: SR in both AP and lateral views is a reliable marker for predicting ARMs severity. SC may provide complementary insights. Routine SR assessment is recommended in newborns with ARMs.