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Mycetoma is a neglected tropical disease characterised by chronic, granulomatous inflammation of the subcutaneous tissues, often leading to disfigurement, disability, and significant socioeconomic burdens. Caused by a diverse array of bacterial and fungal pathogens, eumycetoma is predominantly driven by Madurella mycetomatis , and current treatment strategies are limited and often ineffective. Conventional antifungal therapies, such as itraconazole, require prolonged administration, frequently combined with surgical interventions, yet cure rates remain suboptimal, and recurrence is common. The formidable protective grain, comprising microbial material, melanin, and host-derived substances, acts as a physical and biochemical barrier, impeding the penetration and efficacy of drugs. Additionally, issues such as toxicity, resistance, and high costs further complicate management, underscoring the urgent need for novel therapeutic strategies. Recent advancements in computational drug discovery, particularly molecular docking, offer promising avenues to accelerate the identification of effective anti-mycetoma agents. Molecular docking simulates the interaction between small molecules and target proteins, enabling rapid virtual screening of large compound libraries, including natural products, existing drugs, and synthetic molecules, against key pathogenic targets. This structure-based approach helps prioritise candidates with high binding affinity, guiding subsequent experimental validation and reducing both time and financial costs associated with traditional drug development. When integrated with artificial intelligence (AI) and machine learning (ML), these methods can enhance predictive accuracy, uncover novel bioactive scaffolds, and facilitate the repurposing of FDA-approved drugs such as montelukast and vilanterol. Key molecular targets in M. mycetomatis include enzymes and pathways critical for pathogen survival and virulence, notably cytochrome P450 (CYP51), dihydrofolate reductase (DHFR), chitin synthase, melanin biosynthesis pathways, and metal ion acquisition systems. Melanin production, via DHN-melanin, DOPA-melanin, and pyomelanin pathways, contributes to grain pigmentation and structural integrity, while metal ions such as iron and zinc are vital for enzymatic activities, grain formation, and fungal virulence. Disrupting metal ion homeostasis through targeting zincophores, siderophores, and zinc-binding proteins represents a promising therapeutic strategy to weaken grain robustness and enhance drug penetration. Despite the potential of molecular docking, limitations such as reliance on homology models, static protein structures, and the absence of cellular context necessitate complementary approaches, including molecular dynamics simulations and in vitro validation. These combined efforts can refine candidate compounds, optimise binding affinities, and predict pharmacokinetic properties. Furthermore, integrating docking results with clinical data and global collaboration platforms can accelerate the discovery of affordable, effective treatments tailored to endemic regions. In conclusion, leveraging molecular docking and computational methods to target essential M. mycetomatis pathways offers a promising frontier in mycetoma research. By identifying novel inhibitors and understanding pathogen biology at a molecular level, these approaches can inform targeted therapies, reduce treatment durations, and improve patient outcomes. Future research should focus on validating computational predictions experimentally and translating these findings into clinical practice, with an emphasis on accessible, cost-effective interventions for vulnerable populations affected by this neglected disease.

In the case of Proteus vulgaris infection, the increased occurrence of multidrug-resistance strains has become a critical challenge in the treatment of urinary tract diseases. Therefore, using plant extracts as eco-friendly antibacterial provides an attractive solution to battle bacterial infection. The current study investigates the antibacterial and antihemolytic activity of nine medicinal plant extracts against P. vulgaris. Citrus limon extract at 150 µg/ml exhibited the highest antimicrobial action against P. vulgaris (the inhibition zone diameter; 22.7 mm). Zinc oxide nanoparticles (ZnO NPs) are synthesized using the plant extracts of C. limon, Allium sativum, Sonchus bulbosus, Allium cepa, and Asparagus racemosus. The antibacterial activity of ZnO NPs synthesized using C. limon extract at 150 µg/ml is significantly increased (33.8 mm). ZnO NPs synthesized using A. cepa, A. racemosus , and C. limon plant extracts are effectively protective for human red blood cells. The ZnO NPs synthesized using C. limon extract are characterized using UV–Visible spectroscopy, FTIR, XRD, and TEM. FTIR revealed that the plant extracts may serve as reducing and capping agents of ZnO NPs. XRD spectra confirmed the crystallinity of ZnO NPs. TEM image demonstrated the formation of spherical shapes of ZnO NPs with an average size of 37.05 nm. SEM of P. vulgaris cells treated with ZnO NPs showed cellular morphological damage compared to the untreated cells. ZnO NPs are synthesized by gamma irradiation as a clean and novel method. This study recommended the promising uses of the biosynthesized ZnO NPs using plant extracts as a natural, unique approach, to control the pathogenicity of P. vulgaris .

The progressively increasing antimicrobial-resistant Acinetobacter baumannii infections have enforced the use of colistin as the last option for therapy, resulting in the colistin resistance evolution. This work aimed to study the pmrCAB expression in A. baumannii isolates as well as the presence of the mcr-1 gene. Colistin MICs of 100 A. baumannii isolates were measured using the broth microdilution assay. In four colistin-susceptible and four colistin-resistant isolates, the relative expression of the  pmrA, pmrB , and  pmrC  genes was determined using reverse transcription PCR, and then selected isolates were sequenced using the Sanger technique. Finally, the  mcr-1  gene was detected using conventional PCR. The colistin resistance rate among the studied isolates was 49%. The expression levels of pmrA and pmrB were statistically significantly higher in colistin-resistant isolates than in colistin-susceptible ones, while the pmrC expression had no statistically significant change. There was a weak positive correlation between colistin MICs and the expression levels of each of the pmrA and pmrB genes. By sequencing, two colistin-resistant strains with low pmrCAB expression showed insertion mutations 3277188_3277189T in pmrB and 1185149_1185150T in pmrC . Only one isolate (1%) was positive for the presence of mcr-1 . We concluded that pmrCAB increased expression and/or mutations may cause colistin resistance in A. baumannii . However, increased pmrC expression may not necessarily result in colistin resistance. In Egypt, this is the first study to reveal the existence of mcr-1 in A. baumanni . This should attract attention in clinical settings due to the ultimate tendency of spreading colistin resistance.

Forecasting energy consumption in Saudi Arabia for the period from 2020 until 2030 is investigated using a two-part composite model. The first part is the frontier, and the second part is the autoregressive integrated moving average (ARIMA) model that helps avoid the large disparity in predictions in previous studies, which is what this research seeks to achieve. The sample of the study has a size of 30 observations, which are the actual consumption values in the period from 1990 to 2019. The philosophy of this installation is to reuse the residuals to extract the remaining values. Therefore, it becomes white noise and the extracted values are added to increase prediction accuracy. The residuals were calculated and the ARIMA (0, 1, 0) model with a constant was developed both of the residual sum of squares and the root means square errors, which were compared in both cases. The results demonstrate that prediction accuracy using complex models is better than prediction accuracy using single polynomial models or randomly singular models by an increase in the accuracy of the estimated consumption and an improvement of 18.5% as a result of the synthesizing process, which estimates the value of electricity consumption in 2030 to be 575 TWh, compared to the results of previous studies, which were 365, 442, and 633 TWh.

Background Testicular injury is one of the most serious problems associated with diabetes mellitus. The present study aimed to compare the effects of two different doses of nobiletin and analyze its mechanisms of action against diabetes-induced testicular impairment in rats. Methods and results Streptozotocin injection was used to induce diabetes. Diabetic rats received nobiletin orally at 10 or 25 mg/kg daily for 30 days. Diabetic rats displayed significant elevations in glucose, glycosylated hemoglobin (HbA1c), Homeostatic Model of Insulin Resistance (HOMA-IR), and pro-inflammatory cytokines, while the serum levels of insulin, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were significantly reduced. Histological changes to positivity for caspase-3 and decreased androgen receptors (AR) immunoexpression were observed in diabetic rats. Both doses of nobiletin improved hyperglycemia, reduced pro-inflammatory cytokines, and augmented insulin, testosterone, LH, and FSH levels. LH and FSH receptors and cytochrome P450 17 α-hydroxylase (CYP17A1) were markedly downregulated in terms of both gene and protein expression in testicular tissues of the diabetic group, effects that were markedly ameliorated with both doses of nobiletin. In addition, both doses significantly reduced lipid peroxidation and caspase-3 immunoexpression and improved the activity of the antioxidant enzymes and AR in testicular tissues of the diabetic group . Conclusion Both nobiletin doses showed protective effects against diabetes-induced testicular injury by reducing oxidative stress, hyperglycemia, inflammation, and caspase-3 and upregulating the hypophysis–gonadal axis and AR. The high dose of nobiletin was more effective than the lower one.

The topic of this investigation was to evaluate the microbial contamination of household sponges, biosynthesize of silver nanoparticles (Ag NPs) by Gliocladium deliquescens cell-free supernatant, and estimate the efficiency of Ag NPs as an acceptable disinfectant. The 2 3 factorial design was applied for the optimization of Ag NPs synthesis. Silver nitrate (AgNO 3 ) concentration was the main positive impact on Ag NP biosynthesis. Various gamma irradiation doses were used in Ag NP production where the highest yield production was at 25.0 kGy. Ag NPs were characterized by UV–Vis. spectroscopy, The Fourier-transform infrared spectroscopy analysis (FTIR), dynamic light scattering (DLS), X-ray diffraction (XRD), and transmission electron microscope (TEM). Ag NPs were monodispersed spherical-shaped with 9.68 nm mean size. Two hundred sponge samples that were collected from different Egyptian household furniture and kitchens were highly contaminated by various contaminants including Salmonella spp., Staphylococcus spp., coliform bacteria, Gram-negative bacteria, yeasts, and molds. Ag NPs showed functional antimicrobial activity against all the microbial contaminants; Salmonella spp. was completely inhibited by Ag NP (50.0 μg/mL) treatment. The Ag NPs have the maximum inhibition zone against Salmonella spp. (14 mm) compared with the Staphylococcus spp. (12.3 mm). The minimum inhibitory concentration (MIC) of Ag NPs against Salmonella spp. and Staphylococcus spp. were 6.25 μg/ mL and 12.5 μg/ mL, respectively. The antibiofilm activity of Ag NPs was the highest at the concentration of 50.0 μg/mL recording 63.3 % for Salmonella spp. and 54.5 % for Staphylococcus spp. Ag NPs may find potent disinfectant applications for household purposes.

Gadodiamide (GDD) is a widely used magnetic resonance imaging (MRI) contrast agent. It is available only as intravenous injection. Unfortunately, it exhibits a high renal toxicity. In this respect, the author investigated the possibility of developing nanofibers (NFs, one-dimensional (1D) nanostructures) of GDD that would be promising for oral administration in intestinal imaging. NFs are prepared by electrospinning technique in which a strong electrostatic field is applied on a polymer solution. NFs were prepared by coaxial electrospinning technique using Eudragit S100 (ES 100) as a shell layer and GDD loaded with polyvinylpyrrolidone K90 (PVP K90) and hydroxypropyl-beta-cyclodextrin (HP-β-CyD) as core fibers. Compatibility study of the NFs ingredients was attested through ATR and DSC investigations. Thermogravimetric analysis of NFs was done to insure its stability. In vitro release of GDD in the intestinal medium with different pH values was measured. In vitro cytotoxicity test was done to prove its safety. Additionally, stability of NFs to perform its function was examined by X-ray. NFs experienced high entrapment efficiency of about 94.3% ± 3.1%. The ingredients of NFs were compatible through FT-IR and DSC study. The in vitro release data of GDD from coaxial NFs were slow (˂14%) in pH 1.2 till 2 h, while at pH 7.4 it showed burst release of about 12% in the first 2 min. Thermogravimetric analysis proved the NFs are stable. The in vitro cytotoxicity study proved the safety of NFs. Using mammography, the coaxial NFs behaved the same as GDD plain indicating its ability to be a contrasting agent. Coaxial NFs of GDD as a core with PVP K90 and HP-β-CyD and ES 100 as a shell were stable and efficient as oral imaging dosage form for the intestine. It might be a prospective theranostic.

Background Despite recent advances in therapy modalities of colorectal cancer (CRC), it is still the third cause of cancer-related deaths worldwide. Thus, the search for new target therapies became mandatory. DDR1 is a collagen receptor that has a suggested role in cellular proliferation, tumor invasion, and metastasis. Material and methods Forty-eight cases of CRC, 20 of CR adenoma, and 8 cases of non-tumoral colonic tissue were subjected to immunohistochemistry by DDR1 and β - catenin antibodies. Results were compared among the different studied groups and correlated with clinicopathologic data and available survival data. Also, the expression of both proteins was compared versus each other. Results were compared among the 3 studied groups and correlated with clinicopathologic and survival data. Results It revealed a stepwise increase of DDR1 expression among studied groups toward carcinoma ( P = 0.006). DDR1 expression showed a direct association with stage D in the modified Dukes’ staging system ( P = 0.013), higher-grade histologic types ( P = 0.008), and lymph node invasion ( P = 0.028) but inverse correlation with the presence of intratumoral inflammatory response (TIR) ( P = 0.001). The shortest OS was associated with strong intensity of DDR1 ( P = 0.012). The DDR1 and β - catenin expressions were significantly correlated ( P = 0.028), and the combined expression of both was correlated with TNM staging ( P = 0.017). Conclusion DDR1 overexpression is a frequent feature in CRC and CR adenoma. DDR1 is a poor prognostic factor and a suppressor of the TIR. DDR1 and β - catenin seem to have a synergistic action.

Background Globally, breast cancer ranks among the most common malignancies and has a high mortality rate. Invasive breast carcinoma of no special type (IBC-NST) presents a heterogeneous group with variable prognosis. Identifying reliable biomarkers is crucial for improving treatment strategies and predicting outcomes. This study investigates the immunohistochemical expression of parathyroid hormone-related protein (PTHrP) and ezrin in IBC-NST and their correlation with clinicopathological features and overall survival. Methods This retrospective study analyzed 160 paraffin-embedded tissue samples, including 123 IBC-NST and 37 normal breast tissues, collected from patients treated at Menoufia University Hospital during the period from January 2018 to January 2022. Immunohistochemical staining for PTHrP and ezrin was performed, and expression levels were quantified using the H score. Results PTHrP expression was significantly higher in IBC-NST than in adjacent DCIS and normal tissues ( p  < 0.001). High PTHrP percent of expression was associated with metastasis ( p  = 0.009), bone metastasis ( p  = 0.012), and lymphovascular invasion ( p  = 0.037). Ezrin expression was also significantly elevated in IBC-NST, with higher H score values correlating with high tumor grade ( p  = 0.002), high N stage ( p  = 0.045), advanced AJCC stage grouping ( p  = 0.0043) and metastasis ( p  = 0.001). A significant positive correlation was observed between PTHrP and ezrin expression (rs = 0.341, p  < 0.001). Kaplan-Meier analysis showed that high ezrin expression, in terms of intensity ( p  = 0.007) and H score ( p  = 0.002), was linked to poorer survival. Conclusion The study highlights the significant roles of PTHrP and ezrin in breast cancer progression. Elevated levels of these proteins are associated with more aggressive disease, suggesting their capability as prognostic indicators and treatment targets in breast cancer. Additional studies are required to investigate their interaction and collective influence on breast cancer metastasis and treatment.

This study investigated the effects of emulsified clove oil supplementation on growth performance, carcass characteristics, blood biochemical parameters, antioxidant status, and meat quality of broiler chickens fed a low-energy diet. A total of 252 day-old Cobb broiler chicks unsexed were randomly assigned to three groups: a control group, T1 (300 mg/kg clove oil with emulsifier and 200 kcal energy reductions), and T2 (300 mg/kg clove oil without emulsifier and 200 kcal energy reduction). Both treatments improved body weight gain and feed conversion ratio, with T1 showing superior efficiency due to enhanced nutrient absorption. Carcass analysis revealed increased yields of breast and thigh, especially in T2, while T1 supported more balanced growth. Blood biochemical results indicated improved protein metabolism and lipid profile without adverse effects on liver or kidney function. The antioxidant capacity was significantly elevated in both treated groups, resulting in a reduction of oxidative stress markers. Clove oil supplementation also altered the fatty acid profile of broiler meat by increasing monounsaturated fatty acids and maintaining polyunsaturated fatty acid levels. Notably, the emulsifier in T1 significantly reduced abdominal microflora by up to 55% compared to other groups. MALDI-TOF/MS Biotyper ® identified the dominant microorganisms as Bacillus altitudinis /pumilus. These findings highlight the potential of emulsified clove oil as a functional feed additive for enhancing broiler productivity and health.