Mostafa M. Bahaa

Adiponectin is a polypeptide adipocytokine consist of 244 amino acid that synthesized and released from different tissues and organs such as skeletal muscles, adipose tissue, brain, placenta and bo...

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, β-cell dysfunction, and chronic low-grade inflammation. Doxycycline exhibits a

Background: Non-alcoholic fatty liver disease (NAFLD) represents a prevalent, long-standing hepatic condition marked by the accumulation of fat in the liver and varying degrees of fibrotic changes. Ketotifen, a mast cell stabilizer, has been proposed to modulate inflammation and fibrogenesis, but clinical evidence is limited. Objective: To assess the effectiveness and safety of ketotifen vs vitamin E in individuals with NAFLD. The primary outcome was the change in hepatic steatosis, while the secondary outcomes included modifications in fibrosis-related indices and inflammatory biomarkers. In addition to other biochemical, anthropometric, and metabolic parameters. Methods: In this randomized study, 60 individuals with NAFLD were allocated in a 1:1 ratio into two groups. The vitamin E group was treated with vitamin E, and the ketotifen group received ketotifen for six months. Anthropometric parameters, liver steatosis and fibrosis, lipid profile, glycemic markers, liver enzymes, matrix metalloproteinase (MMP)-9, and tumor necrosis factor (TNF)-α were measured before and after 6 months. Results: Ketotifen treatment resulted in significant improvements in hepatic steatosis and disease activity compared with vitamin E, including lower steatosis and FibroScan-AST (FAST) score. Fibrosis severity was also reduced, with significant decreases in fibrosis score and fibrosis index (FIB-4) index, whereas Metabolic-Associated Steatosis Combined with Keratin-18 (MACK-3) score showed no significant between-group change. Glycemic outcomes improved significantly with ketotifen, including reductions in HOMA-IR, fasting blood glucose, and fasting insulin. Ketotifen also significantly reduced AST, TNF-α and MMP-9, and improved central adiposity measures (hip circumference, waist–stature ratio. No significant differences were observed for lipid profile, body weight, body mass index, or HbA1c. Ketotifen was generally well tolerated; drowsiness was the most common adverse event. Conclusion: Ketotifen exerts superior hepatoprotective, anti-inflammatory, antifibrotic, and insulin-sensitizing effects compared with vitamin E in NAFLD. These findings suggest that ketotifen may offer a promising adjunctive therapy for NAFLD. Clinical Trial Registration: NCT05616442.

The exact etiology of ulcerative colitis (UC) remains incompletely understood. However, substantial evidence implicates multiple signaling pathways in its pathogenesis, including interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3), wingless/Int1 (Wnt), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and NLR family pyrin domain-containing 3 (NLRP3). Atorvastatin and nitazoxanide have demonstrated anti-inflammatory, antioxidant, and immunomodulatory properties that may target these signaling pathways. The aim of this study was to investigate the coloprotective effects of atorvastatin and nitazoxanide in an experimental model of UC. Colitis was induced by intracolonic administration of acetic acid (AA) in rats. A total of 32 rats were randomly assigned to four groups (n = 8 each): normal control, colitis, atorvastatin-treated, and nitazoxanide-treated groups. Disease severity was assessed via colon length, weight, disease activity index, and histopathological evaluation. Tissue levels of SIRT1, mTOR, HO-1, Nrf2, STAT3, AMPK, and Dickkopf-related protein 1 (DKK1) were measured, along with colonic gene expression of NLRP3, Wnt, IL-6, TNF-α, and DKK1. Additionally, TNF-α and IL-6 protein expressions were assessed by immunohistochemistry. Intracolonic AA administration caused significant biochemical, inflammatory, and structural damage to the colon. Both atorvastatin and nitazoxanide significantly attenuated colitis, as evidenced by reduced disease activity scores, histological improvement, and decreased expression of colonic mTOR, NLRP3, DKK1, IL-6, TNF-α, and STAT3. Conversely, both agents upregulated HO-1, Nrf2, SIRT1, Wnt, and AMPK levels. Histologically, treated groups exhibited partial restoration of normal mucosal architecture, with fewer irregular crypts and reduced lymphoplasmacytic infiltration. Atorvastatin and nitazoxanide ameliorated experimental colitis through modulation of inflammatory and oxidative stress pathways.

Crohn’s disease and ulcerative colitis (UC) are among the intestinal conditions that make up the category known as inflammatory bowel disease. Globally, UC prevalence and incidence are currently rising. There was substantial evidence that many pathways were involved in the pathophysiology of UC. Of these pathways, interleukin 6 (IL-6)/signal transducer and activator of transcription 3 (STAT3), mammalian target of rapamycin and AMP-activated protein kinase (AMPK), Sphingosine kinase (SPHK)/ Sphingosine-1-phosphate, nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase (HO-1). While small-molecule pharmaceuticals and biologics are available to treat patients with UC, approximately one-third of people receiving treatment do not get better. To find an effective remedy for UC patients, new therapy and medication repurposing have therefore been thoroughly researched. Several medications, including rosiglitazone, amlodipine, felodipine, atorvastatin, metformin, pentoxifylline, nitazoxanide, nifuroxazide, carbocisteine, levetiracetam, topiramate, nicodamid, and vildagliptin, have been shown to have positive effects on multiple organs through their anti-inflammatory properties. Furthermore, data on gut barrier integrity, oxidative stress, and inflammatory pathways showed that these medications had a major favorable impact on these parameters in both cellular and clinical models of UC. Using the findings of in vitro, in vivo, and clinical investigations, the positive effects of these medications on UC are thoroughly outlined and examined in the present research. Having a better knowledge of these protective benefits and the basic mechanisms may make it possible for UC patients to take these medications effectively.

Mucormycosis is a rapidly progressive opportunistic fungal infection associated with high morbidity and mortality, especially in immunocompromised patients. In resource-limited settings, management is further hindered by delayed diagnosis and restricted access to safer antifungal formulations. To evaluate survival and renal outcomes among patients with mucormycosis treated with different antifungal regimens. A retrospective review was conducted on 19 patients diagnosed with mucormycosis. Clinical features, comorbidities, antifungal therapy, complications, and outcomes were analyzed. Patients were categorized into five treatment groups based on antifungal regimens. Survival and renal outcomes, including acute kidney injury (AKI) and renal recovery, were assessed. Most patients were diabetic (94.7%), and 52.6% had concurrent or recent COVID-19 infection. All had paranasal sinus involvement, with orbital or palatal extension in 68.4% and CNS involvement in 42%. AKI developed in 68.4% of cases, more common with traditional amphotericin regimens (75%) than with liposomal amphotericin (33.3%). Among those with AKI, 38.5% recovered, while 53.8% progressed to chronic kidney disease. Hypersensitivity reactions occurred in 31.6%, mainly with traditional amphotericin. Overall survival was 84.2%, and prolonged antifungal therapy (> 40 days) with early surgical debridement improved outcomes. The study highlights a substantial gap between international guidelines and real-world practice in low-resource environments, where inconsistent access to liposomal amphotericin limits optimal management. Nevertheless, with early diagnosis, aggressive surgical intervention, and vigilant renal monitoring, favorable outcomes are achievable even with traditional amphotericin. Improving national antifungal procurement, strengthening stock management, and subsidizing liposomal formulations could significantly enhance mucormycosis care in resource-limited settings.

Background: Peroxisome proliferator‐activated receptor α (PPARα) has been reported to exert protective roles in immune‐mediated intestinal diseases through inhibition of interleukin‐6 (IL‐6)‐induced signal transducer and activator of transcription factor 3 (STAT3) activation. Aim: To investigate the potential anti‐inflammatory effect of fenofibrate, as an add‐on therapy to mesalamine, on IL‐6/STAT3 and nitric oxide (NO) in patients with ulcerative colitis (UC). Methods: This pilot, double‐blind, randomized, controlled trial included 60 patients diagnosed with mild‐to‐moderate UC. Patients were randomly allocated into two groups. The placebo group ( n = 30) received placebo plus mesalamine 1 g three times daily, and the fenofibrate group ( n = 30) received mesalamine 1 g three times daily and fenofibrate 160 mg once daily. The study duration was 6 months. The severity of UC was evaluated using the Disease Activity Index (DAI), and quality of life (QoL) was assessed using the Short Form‐36 questionnaire (SF‐36). Serum levels of IL‐6, NO, C‐reactive protein (CRP), and STAT3 were measured for all patients. Results: After treatment, both groups showed a significant reduction in DAI, IL‐6, STAT3, NO, and CRP, along with an increase in SF‐36 scores. Furthermore, the fenofibrate group demonstrated a significantly greater decrease in DAI ( p = 0.0002), IL‐6 ( p = 0.04), STAT3 ( p = 0.004), NO ( p = 0.013), and CRP ( p = 0.034), as well as a greater increase in SF‐36 ( p = 0.04) compared with the placebo group. Conclusion: Fenofibrate may represent a promising add‐on therapy in patients with mild‐to‐moderate UC by modulating inflammation and improving QoL. Trial Registration: NCT05753267