Purpose A multitude of inflammatory cells and chemical mediators initiate a complex cascade that ultimately leads to hepatocyte death and a systemic inflammatory response. This research aimed to investigate the potential effects of sildenafil and neem (Azadirachta indica) extract, in both conventional and nanoparticle (NP) forms, in the treatment of moderate acute liver damage induced by orogastric carbon tetrachloride (CCL4).

Methods To induce moderate acute hepatic damage a single oral dosage of CCL4 (2.5 mL/kg body weight) was provided 24 h before euthanasia. In liver damage-induced CCL4, sildenafil and neem extract were given in conventional and nanoparticle (PLGA or niosome) forms. To find histological anomalies and hepatic changes, behavioral, biochemical, histopathological, and immunohistochemical methods were used.

Results The findings indicated that sildenafil and/or neem extract, especially in NP combination, significantly mitigated CCL 4-induced acute moderate liver damage. Indicators of liver function, including aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), albumin, bilirubin and gamma-glutamyl transferase (GGT), shown improvement, particularly with the nanoparticulation of both therapies. Treatment, particularly in NP forms, improved the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase activity (GPx) in liver tissues. A significant reduction in NF-κB expression in hepatic tissue was shown in treatment groups. Also, medication resulted in lower levels of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), caspase-3, and transforming growth factorbeta (TGF-β) in the liver tissue homogenates. Liver function was more significantly improved by the drug-NP combination. Conclusions This study verified the beneficial therapeutic effects of the combination of sildenafil and neem extract, particularly in NP forms, using biochemical, histological, and immunohistochemical analyses in a rat model of liver damage

Acute renal failure (ARF) is a sudden, significant, and often reversible decline in kidney function, with 25% of all hospital-administered pharmaceuticals potentially causing nephrotoxicity. The study investigates the effectiveness of a novel nanoparticle (NP) formulation of glutathione (GSH) and Lepidium sativum (LS) in improving therapeutic outcomes in a rat model of ARF. Sixty adult male albino rats were allocated into ten groups, comprising six rats each, for the study. ARF was created by daily gentamicin (GN) administration for seven consecutive days and various treatment protocols, including chitosan (CS) NPs, spanlastics NPs, as well as conventional, NP formulations of GSH, LS, and their respective combinations. The effect was evaluated through various tests, and properties of nanoparticles were confirmed through characterization processes. The NP compositions markedly enhanced renal function, as seen by reduced urine concentrations of albumin and glucose. Furthermore, the serum concentrations of creatinine (SCr), blood urea nitrogen (BUN), and cystatin C were decreased. Tissue concentrations of nitrite, superoxide dismutase (SOD), and malondialdehyde (MDA), as markers of oxidative stress, were enhanced by both conventional and NP formulations. Additionally, they decreased inflammatory markers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). Histological analysis and immunohistochemical testing revealed that the combination therapy, particularly with the nanoforms, significantly decreased caspase 3 cellular immunoexpression, a sign of kidney cellular damage. The findings show that the ARF renal damage is

considerably reduced when NPs containing GSH and LS are administered together. The study suggests a promising pharmacological approach for enhancing kidney regeneration and preserving renal function, potentially aiding in new therapeutic interventions for ARF treatment.

This study assessed the neuroprotective potential of empagliflozin (EMPA) as antidiabetic drug on glucose metabolism, comparing it to rivastigmine (RIVA) as standard treatment for Alzheimer's disease (AD), and their combination. Male rats were sorted into five groups. Group I served as the control, while groups II, III, IV, and V received the scopolamine plus heavy metal mixture for AD induction. Groups III and IV were administered RIVA and EMPA, respectively, and group V received both treatments. Cognitive function was evaluated behaviorally. Subsequently, glucose levels, acetylcholinesterase, oxidative stress, and inflammatory markers were assessed. Alongside the brain histopathological changes, the expression of phosphorylated tau protein was assessed. Moreover, glycolytic enzymes and glucose transporters were assessed using PCR analysis. The findings were attributed to a notable suppressive impact of EMPA on lipid peroxidation, acetylcholinesterase, glucose levels, phosphorylated tau protein, pro‐inflammatory cytokines, and neuropathological changes, while enhancing antioxidant and interleukin‐10 levels. It also improves glucose metabolism. The findings suggest that EMPA may be a viable candidate for future therapeutic exploration in AD, which has a multifaceted mechanism of action encompassing anti‐neuroinflammation, antioxidant stress, and enhanced glucose metabolism, as well as decreased acetylcholinesterase activity and phosphorylated tau protein levels. Interestingly, combined treatment showed a superior effect than EMPA alone.
 

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
 

Background

The cesarean scar defect (CSD), or niche, is one of the emerging complications after cesarean section (CS), potentially leading to symptoms such as abnormal uterine bleeding, pelvic pain and secondary infertility.

Objectives

To determine the prevalence of CSD among women attending the outpatient clinic at Women’s Health Hospital, Assiut university, Egypt, and to identify the possible CSD-related symptoms and risk factors for CSD formation.

Methods

This cross-sectional observational study included 234 women with a history of CS performed more than one year before recruitment, between June 2022 and December 2023. Participants underwent 2D transvaginal ultrasound to detect CSD, defined as an indentation of ≥ 2 mm depth at the CS scar site. Data collected encompassed demographic, obstetric, and variable symptoms and analyzed using univariate analysis and multiple logistic regression …

Background

Blood loss is one of the important complications during cesarean section (CS). Previous reports have shown that misoprostol is effective in reducing blood loss during and after CS. However, the optimum time for its administration to decrease the amount of PPH is still under discussion.

Objective

To compare the effect of preoperative and postoperative administration of sublingual misoprostol (400 μg) in reducing the amount of blood loss during and 24 hours after CS.

Setting

Obstetrics and Gynecology Department, Faculty of Medicine, Assiut University, Assiut, Egypt, between January 2017 and July 2018.

Study Design

A prospective, randomized clinical trial.

Methods

Four-hundred thirty women fulfilling the inclusions criteria: elective lower segment CS at term (≥37 weeks) with normal fetal heart tracing who accepted to participate in the study. Patients were divided into two groups; Patients assigned to group 1 received 400 μg sublingual misoprostol immediately after urinary catheterization and before skin incision, while patients assigned to group 2 received sublingual misoprostol immediately after skin closure. The primary outcome was the estimation of intraoperative and postoperative blood loss for 24 hours.

Results

There was a significant reduction in the intraoperative blood loss in group 1 compared with group 2 (403.51 ± 72.99 vs. 460.99 ± 74.66 ml, respectively). Also, there was a significant reduction in postoperative blood loss in group 1 compared with group 2 with a statistical significance (169.45 ± 12.03 vs. 195.77 ± 13.34 ml, respectively). Postoperative hemoglobin and Hematocrit values were significantly higher in group 1 …