SAID SHEHATA

Imidacloprid (IMI) is a commonly used chloronicotinyl insecticide, although it has low specificity to humans, long-term exposure would induce neurotoxicity through cholinergic signaling disruption and ferroptosis activation. The current investigation aimed to explore the neuroprotective impact of deferiprone (DFP), an iron chelator, against IMI-induced neurotoxicity and whether co-administration with everolimus (EVR), an mTOR inhibitor known to induce autophagy and potentially enhance ferritinophagy, would alter this effect. Adult male Wistar rats were assigned randomly to four different experimental sets: control, IMI, IMI + DFP, and IMI + DFP + EVR groups. They were given IMI (90 mg/kg/day, p.o.), DFP (125 mg/kg/day, p.o.), and EVR (1 mg/kg/day, i.p.) for 30 days. Rats were subjected to neurobehavioral assessments including open-field, rotarod, Y-maze, and tail-immersion tests. Rats' cortices were examined histologically, and acetylcholinesterase (AChE) expression was evaluated immunohistochemically. Several biochemical markers were assessed including oxidative stress markers such as reduced and oxidized glutathione, superoxide dismutase and malondialdehyde, in addition to ferroptotic markers including acyl-CoA synthetase long-chain family member-4, lysophosphatidylcholine acyltransferase-3, iron responsive element binding protein-2, ferritin heavy chain-1, and transferrin receptor-1. IMI administration led to marked biochemical derangements, cortical damage, reduced AChE expression, altered spontaneous motor function, locomotor coordination, spatial memory, and pain threshold while increasing anxious behaviours. DFP ameliorated oxidative stress, reduced ferroptotic markers and alleviated the neurobehavioural defects. Meanwhile, co-administration of EVR abolished these protective effects, consistent with enhanced autophagy-associated iron release and ferroptosis activation. Overall, these findings support the therapeutic potential of DFP against IMI-induced neurotoxicity and highlight ferroptosis as a promising therapeutic target in pesticide-related neurodegeneration.

The in ovo-injection technique was employed as an early-life nutritional strategy to improve the health and productivity of birds by delivering nutrients and bioactive compounds directly to the developing embryo. This study explored the innovative use of in ovo administration of nano-lauric acid (NLA) as a strategy for the metabolic programming of broiler chicks. The goal was to improve hatchability, stimulate hepatic antioxidant activity, regulate growth-related genes, and support intestinal development in newly hatched chicks. A total of 400 fertile eggs from a 40-week-old Arbor Acres breeder flock were randomly divided into four treatment groups: a non-injected control group (CN), a vehicle-injected control group (CP; 0.1 mL of sterile distilled water), and two NLA-treated groups receiving either 2.5 mg/egg (NLA 2.5) or 5 mg/egg (NLA 5) of NLA, each dissolved in 0.1 mL of sterile distilled water. Injections were administered into the yolk sac on day 12 of incubation. Post-hatching, the hatchability percentage was recorded. Serum lipid profiles, hepatic redox status, and the expression level of hepatic genes, nuclear factor erythroid 2-related factor 2 (NRF2), mitochondrial superoxide dismutase 2 (mt-SOD2), and insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) were evaluated. Additionally, the intestinal morphology of the newly hatched chicks was examined. Hatchability % was significantly reduced in the NLA 5 group (80%) compared to the CN (98%), CP (97%), and NLA 2.5 (96%) groups. The findings showed that in ovo injection of NLA at 2.5 mg/egg was therefore identified as optimal, significantly improving lipid metabolism by reducing serum triglycerides, LDL, VLDL, and cholesterol, while increasing HDL cholesterol compared to controls (P < 0.05). Hepatic antioxidant defense was significantly improved through the decrease of malondialdehyde (MDA) and increase of reduced glutathione (GSH) concentrations (P < 0.05). This enhancement was associated with the upregulation of NRF-2 and mt-SOD2 by (4.04; 3.69-folds, respectively) and stimulation of anabolic signaling genes IGF-1 and IGF-2 by (4.08 and 2.3-folds; respectively) (P < 0.05). In addition, intestinal development has been significantly promoted via increased villus height and crypt depth (P < 0.05). Our findings demonstrate that in ovo NLA supplementation at 2.5 mg/egg effectively enhances lipid utilization, activates NRF2-mediated antioxidant pathways, and stimulates anabolic signaling. This targeted nutritional strategy proves to be a safe and effective method for pre-hatch metabolic programming, with significant potential to improve post-hatch health and performance in broilers.

This study aimed to investigate the influence of in-ovo injection of manganese (Mn) on hatchability, hatching weight, bone development and mineralisation, meat quality of breast and thigh, and also the serum and molecular levels of some antioxidants in the post-hatched chicks. About 350 fertile eggs were collected from a Hubbard efficiency plus breeder's flock of 42 weeks old, incubated at normal setting temperature (37.5°C) and relative humidity (RH 60%), and randomly allocated into three treatments. The eggs were labelled and randomly assembled into three groups with four replicates, and 25 eggs each. The treatment was designed as a control non-inoculated group (CN), a vehicle-inoculated group (CP, inoculated with 0.1 mL physiological saline), and a Mn-inoculated group (0.01 mg/egg, dissolved in 0.1 mL physiological saline). The site of injection was the air cell at the broad end of the eggs on the 12th day of incubation. On the day of the hatch, the rate and the hatchling's weight were recorded. The serum-reduced glutathione (GSH) concentrations and superoxide dismutase activity (SOD) were assessed in 7-day-old chicks. On the molecular level, qRT-PCR for nuclear factor erythroid 2-related factor 2 (Nrf2) and superoxide dismutase (SOD) genes was performed in the breast skeletal muscles at post-hatch day 7. Femur proximal metaphysis histo-morphometric analysis was done with computerised morphometric measurements. The thigh and breast meat quality were evaluated. In-ovo inoculation of organic manganese (Mn) showed no significant adverse effects on hatchability (p = 0.51), hatchling weight (p = 0.93), or mortality during the rearing period (p = 0.67). Conversely, Mn supplementation significantly enhanced bone mineralisation and upregulated the expression of antioxidant-related genes, including SOD (p = 0.027) and Nrf2 (p = 0.018), in muscle tissue. Furthermore, in-ovo Mn administration contributed to improved meat quality by significantly reducing fat content (p < 0.01) and pH (p < 0.0001), while increasing ash content (p < 0.0001), potentially extending the shelf life of broiler meat.

BackgroundNon-specific low back pain (NSLBP) has been associated with proprioceptive deficits that may also affect the knee joint.ObjectiveThis study aimed to examine knee proprioception in young adults with NSLBP and to assess dynamic postural stability using the Biodex Balance System (BBS). It further explored whether gender influences these outcomes.MethodsEighty-eight participants, aged 18 to 26 years with a body mass index under 30 kg/m² and diagnosed with NSLBP, were recruited. They were assigned to male (n = 44) and female (n = 44) groups. Assessments included the Oswestry Disability Index (ODI), knee joint repositioning error (JPE) measured with a digital inclinometer, and dynamic balance evaluated with the BBS. The BBS provided overall stability index (OSI), anterior-posterior index (API), and medial-lateral index (MLI) scores. Statistical analyses were performed using SPSS with significance set at p < 0.05.ResultsThere were no significant gender differences in JPE (males: 30.97 ± 3.62; females: 30.28 ± 5.42, p > 0.05) or ODI. BBS outcomes, however, showed elevated OSI (4.2 ± 1.1 compared with 2.5 ± 0.5 in healthy controls, p < 0.01), API (3.8 ± 0.9 compared with 2.0 ± 0.4, p < 0.01), and MLI (3.5 ± 0.8 compared with 1.8 ± 0.3, p < 0.01), indicating impaired dynamic balance. No significant gender differences were observed in BBS indices.ConclusionNSLBP significantly impairs dynamic knee proprioception, as demonstrated by BBS findings. Gender did not influence proprioceptive performance in this cohort.

Vulvovaginal fungal infections remain a major therapeutic challenge due to poor drug penetration, recurrence, and limited efficacy of conventional formulations. Harnessing nanotechnology with a novel delivery platform offers a promising strategy to overcome these barriers. In this study, an innovative olaminogel was designed as an advanced nanocarrier for terconazole (TCZ) to enhance local antifungal therapy via the vaginal route. The formulation was prepared using the ethanol injection method and systematically optimized through a 2 factorial design considering limonene-to-surfactant ratio (factor A), oleylamine-to-drug ratio (factor B), and oleic acid-to-surfactant ratio (factor C). Optimization targeted maximal entrapment efficiency (EE%), minimal particle size (PS), and stable zeta potential (ZP). The optimized olaminogel achieved an EE% of 82.11, nano-metric PS of 217.25 nm, and a ZP of - 33.05 mV. TEM confirmed well-formed vesicles, while FTIR verified successful encapsulation. Further in vitro characterization revealed pseudo-plastic rheology, sustained biphasic drug release, and stability for 3 months. Mucoadhesion testing demonstrated strong adhesion of the olaminogel to vaginal mucosa. Ex vivo permeation across rabbit vaginal mucosa demonstrated significantly deeper penetration (180 µm vs. 55 µm) compared with plain TCZ gel, corroborated by in vivo CLSM imaging. Histopathological studies further confirmed biocompatibility and absence of irritation. Importantly, microbiological evaluation revealed markedly reduced MIC and MFC values, alongside an accelerated fungicidal effect, outperforming TCZ control. Collectively, these findings highlight olaminogel as a novel and potent intravaginal nanocarrier capable of improving drug retention, mucosal penetration, and antifungal efficacy, thereby presenting a next-generation platform for safe and effective management of vaginal fungal infections.

Brain tumors represent some of the most formidable challenges in neuro-oncology due to their aggressive clinical course, resistance to therapy, and profound molecular heterogeneity. Among the emerging regulatory elements reshaping our understanding of tumor biology are long non-coding RNAs (lncRNAs), a diverse class of RNA transcripts that modulate gene expression and cellular behavior without encoding proteins. This review provides an in-depth and integrative examination of the biogenesis, regulatory mechanisms, and functional roles of lncRNAs in brain tumor development and progression. We systematically explore both canonical and non-canonical pathways of lncRNA biogenesis, detailing how these influence structural specificity and molecular interactions. This review synthesized evidence retrieved from PubMed/MEDLINE, Scopus, and Web of Science, covering publications from January 2010 to June 2025. This analysis highlights key gaps, such as context-dependent therapeutic effects that limit translational applicability. A major focus is placed on the interplay between lncRNAs and core oncogenic signaling pathways, including Phosphoinositide 3-kinase (PI3K)/serine/threonine kinase (AKT), Signal Transducer and Activator of Transcription 3 (STAT3), Wingless/Int-1 (Wnt)/β-catenin, and Transforming Growth Factor-Beta (TGF-β), which drive malignant transformation, invasion, stemness, and therapeutic resistance in gliomas. Furthermore, we dissect the molecular functions of lncRNAs as epigenetic regulators, competitive endogenous RNAs (ceRNAs), and structural scaffolds, and discuss their contribution to the dynamic tumor microenvironment. By synthesizing the latest findings, this review underscores the academic and translational importance of targeting lncRNA-associated networks. It also highlights emerging therapeutic approaches, such as antisense oligonucleotides, RNA interference, CRISPR-Cas systems, and natural lncRNA-modulating compounds, which collectively represent a promising frontier in precision medicine for brain tumors. This work offers a critical framework for future research and therapeutic innovation in the lncRNA landscape of neuro-oncology.

Viniferin, a resveratrol-derived compound that belongs to a group of plant-produced stilbenoids, functions as a natural defense against microbial invasion, toxins, infections, and ultraviolet radiation. Alpha-(α-) viniferin (trimer), beta-(β-) viniferin (dimer), delta-(δ-) viniferin (oxidative dehydrodimer), epsilon-(ε-) viniferin (distinct dehydrodimer), gamma-(γ-) viniferin (isomeric oligomer), vitisin A (R-viniferin), and vitisin B (R2-viniferin) are structurally diverse forms with distinct pharmacological activities. Antioxidant studies showed that ε-viniferin exhibited a 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging half-maximal inhibitory concentration (IC₅₀) of about 80 µM. Also, suppression of nuclear factor kappa B, cyclooxygenase-2, and prostaglandin E₂ are anti-inflammatory mechanisms. R2-viniferin demonstrated an IC₅₀ of 9.7 µM against hepatocellular carcinoma HepG2 cells at 72 h, mediated through apoptosis and cell-cycle arrest, according to anticancer studies that demonstrated dose-dependent cytotoxicity. There have been reports of additional activity against models of glioblastoma and prostate cancer. In metabolic disorders, oral α-viniferin (20-40 mg/kg/day) improved lipid and glucose homeostasis in mice fed a high-fat diet, and it additionally improved liver and renal biomarkers such as blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransaminase. Several bacterial strains have shown signs of preliminary antimicrobial action. By reducing excitotoxicity and oxidative stress, viniferins also have neuroprotective effects. They also have anti-melanogenic properties by blocking the tyrosinase and melanogenesis pathways. Collectively, viniferins demonstrate pleiotropic pharmacologic activities by defined molecular mechanisms and quantifiable dose-dependent effects. The properties classify viniferins as new multifunctional drug candidates for discovery and nutraceuticals, but they highlight the need for standardized pharmacologic assays, further preclinical validation, and pharmacokinetic optimization towards clinical use.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder with limited effective pharmacological options. Endoplasmic reticulum (ER) stress and mitochondrial dysfunction have emerged as pivotal pathological mechanisms in PTSD pathophysiology, yet therapies targeting these pathways remain largely unexplored. Citicoline, recognized for its neuroprotective properties and capacity to modulate mitochondrial homeostasis, presents a promising candidate for intervention. This study investigated citicoline's therapeutic efficacy against behavioral and hippocampal molecular abnormalities induced by single prolonged stress (SPS) in male mice. Thirty-six mice were subdivided into control, citicoline (Citi) (100 mg/kg, p.o for 7 days), SPS (2-hour restraint, 20-minute forced swim, ether exposure), and SPS+Citi (SPS followed by citicoline for 7 days) groups. Citicoline administration effectively reversed stress-induced behavioral impairments in social novelty preference, marble burying, and cue-induced freezing. At the molecular level, citicoline restored ER homeostasis by attenuating the toxic unfolded protein response characterized by reductions in phosphorylated protein kinase RNA-like ER kinase, activating transcription factor (ATF) 4, and ATF6 while upregulating the protective X-box binding protein 1. Such improvements were accompanied by reactivation of impaired mitophagy through enhanced PTEN-induced kinase 1 and parkin expression, facilitating clearance of damaged mitochondria and reactive oxygen species. Furthermore, citicoline effectively countered oxidative stress, evidenced by suppressing malondialdehyde-mediated lipid peroxidation while restoring glutathione antioxidant reserves. Citicoline also normalized mitochondrial biogenesis by upregulating peroxisome proliferator-activated receptor gamma coactivator 1-alpha and prevented neuronal apoptosis by suppressing caspase-3. Collectively, these findings establish citicoline as a promising multi-targeted therapeutic candidate for behavioral and hippocampal molecular abnormalities after SPS in male mice.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder with limited effective pharmacological options. Endoplasmic reticulum (ER) stress and mitochondrial dysfunction have emerged as pivotal pathological mechanisms in PTSD pathophysiology, yet therapies targeting these pathways remain largely unexplored. Citicoline, recognized for its neuroprotective properties and capacity to modulate mitochondrial homeostasis, presents a promising candidate for intervention. This study investigated citicoline's therapeutic efficacy against behavioral and hippocampal molecular abnormalities induced by single prolonged stress (SPS) in male mice. Thirty-six mice were subdivided into control, citicoline (Citi) (100 mg/kg, p.o for 7 days), SPS (2-hour restraint, 20-minute forced swim, ether exposure), and SPS+Citi (SPS followed by citicoline for 7 days) groups. Citicoline administration effectively reversed stress-induced behavioral impairments in social novelty preference, marble burying, and cue-induced freezing. At the molecular level, citicoline restored ER homeostasis by attenuating the toxic unfolded protein response characterized by reductions in phosphorylated protein kinase RNA-like ER kinase, activating transcription factor (ATF) 4, and ATF6 while upregulating the protective X-box binding protein 1. Such improvements were accompanied by reactivation of impaired mitophagy through enhanced PTEN-induced kinase 1 and parkin expression, facilitating clearance of damaged mitochondria and reactive oxygen species. Furthermore, citicoline effectively countered oxidative stress, evidenced by suppressing malondialdehyde-mediated lipid peroxidation while restoring glutathione antioxidant reserves. Citicoline also normalized mitochondrial biogenesis by upregulating peroxisome proliferator-activated receptor gamma coactivator 1-alpha and prevented neuronal apoptosis by suppressing caspase-3. Collectively, these findings establish citicoline as a promising multi-targeted therapeutic candidate for behavioral and hippocampal molecular abnormalities after SPS in male mice.

Rare neurological diseases are challenging to diagnose from brain MRI because of their low prevalence, heterogeneous imaging patterns, and limited annotated datasets. Deep learning may support image-level recognition, but results from curated datasets without complete patient-level identifiers require cautious interpretation. This study proposes RareNeuroXNet, a frequency-aware multi-branch attention framework for image-level classification of rare neurological diseases from brain MRI. The objective was to assess whether combining global anatomical, local fine-grained, and frequency-domain representations improves benchmark performance, calibration, and interpretability. RareNeuroXNet uses three complementary branches: a global branch for whole-image representation, a local branch for regional feature extraction, and an FFT magnitude-based frequency branch. Features are refined using CBAM attention, fused, and classified through a fully connected head. The model was evaluated on a balanced curated dataset with five rare neurological disease classes using five-fold cross-validation, ablation analysis, calibration metrics, internal baseline comparison, paired testing against DenseNet121 local-only, and Grad-CAM visualization. MCND was also used as a complementary cross-dataset neurological MRI benchmark, not as same-task external validation. RareNeuroXNet achieved strong image-level internal benchmark performance, with accuracy of 0.9924±0.0061, macro F1-score of 0.9924±0.0061, macro AUROC of 0.9998±0.0002, and macro AUPR of 0.9992±0.0007. Calibration was favorable, with ECE of 0.0052±0.0029 and NLL of 0.0276±0.0159. Ablation results showed that the local branch was the dominant contributor, while FFT and CBAM provided supportive refinement. Compared with DenseNet121 local-only, RareNeuroXNet showed modest classification gains and clearer calibration improvements. RareNeuroXNet demonstrated strong controlled image-level benchmark performance with high discrimination, stable cross-validation behavior, favorable calibration, and Grad-CAM interpretability. However, possible correlated slices, duplicate images, or subject overlap cannot be excluded. Future work should use patient-level, same-task, multi-center external validation and 3D multimodal MRI analysis.

Doxorubicin (DOX), a widely utilized chemotherapeutic agent, is associated with significant adverse effects, including cognitive dysfunction (chemobrain) and depression. Ketamine (KET), the anesthetic, was off-label used as antidepressant and got FDA approval in 2019 for treatment-resistant depression management. Hence, this study investigated the therapeutic efficacy of single [KET(S)] versus repeated [KET(R)] subanaesthetic ketamine in mitigating DOX-induced neurological alterations in rats. Forty-eight adult male Wistar rats were subdivided into four groups: control, DOX, KET(S) (DOX followed by a single KET dose, 15 mg/kg), and KET(R) (DOX followed by repeated KET doses, 15 mg/kg/day for 14 days). Results showed that DOX administration caused marked motor dysfunction, cognitive impairment and depression-like behavior, along with elevated neuroinflammation and disrupted neurotrophic signaling. Both KET regimens improved behavioral performance, suppressed systemic and local inflammation, evidenced by suppressing tumor necrosis factor-alpha and nicotinamide adenine dinucleotide phosphate oxidase activity. Also, KET(R) suppressed phosphorylation of key neurotransmitter transporters: phospho T53-dopamine transporter, phospho S563-glutamate transporter-1, and phospho T276-serotonin transporter, which led to enhanced hippocampal brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling. Notably, KET(R) produced superior behavioral and biochemical improvements compared to KET(S). Histopathological examinations corroborated these findings. Collectively, these data suggest that KET, particularly when administered repeatedly at low doses, could be a promising adjunctive therapy to enhance quality of life for cancer patients undergoing DOX chemotherapy. However, because key intermediate nodes were not directly measured and KET-only control groups were not included, the proposed mechanistic cascade should be regarded as a hypothetical integrative model that warrants further validation.

This study investigated the neurobehavioral toxicity of Acetamiprid (ACP), a neonicotinoid insecticide, in male rats and evaluated the potential neuroprotective effects of Resveratrol (RSV), a natural antioxidant found in grapes and peanuts. Forty rats were divided into four groups (Control, ACP 25 mg/kg, RSV 20 mg/kg, and ACP + RSV) and treated orally for 90 days. Assessments included behavioral testing for anxiety and cognition, biochemical analysis of oxidative stress and inflammatory markers (GSH, CAT, MDA, TNF-α), and gene expression profiling of the Pi3k/Akt/BDNF pathway and p38 Mapk and Nbn genes. Histopathological and Tau immunostaining examinations were also conducted. ACP exposure significantly induced anxiety-like behavior and cognitive impairment. The ACP group exhibited marked oxidative stress, apoptosis, and elevated inflammatory marker. ACP altered the expression of genes associated with neuronal survival and repair. Histology confirmed neurodegeneration, necrosis, and gliosis across various brain regions. While ACP causes neurological and oxidative damage, co-treatment with RSV maintains neurobehavioral function and mitigates cellular injury, suggesting its efficacy as a protective agent against ACP-induced neurotoxicity.

Workplace environment in the furniture-making industry can have significant implications for workers' health, especially their mental health. The current study aimed to evaluate the prevalence of sleep problems and insomnia and their relationship with serum melatonin and oxidative marker levels. Fifty male employees in the carpentry department and 50 administrative controls participated in this investigation. The levels of noise and respirable and total dust in the carpentry section were measured. The insomnia severity index and Pittsburgh sleep quality index (PSQI) questionnaires were utilized. Additionally, the levels of melatonin and malondialdehyde (MDA) were evaluated. The mean value of respirable wood dust was 1.9 ± 0.8 mg/m, exceeding international standards but below the national limit. Noise levels exceeded both national and international regulations, measuring 96.8 ± 6.1 dB. Carpenters had significantly higher mean PSQI global scores and insomnia index values than the controls. 66% of carpenters reported poor sleep quality, compared to 14% of the controls. Carpenters had significantly higher MDA and lower melatonin levels. Carpenters with poor sleep quality exhibited significantly lower melatonin and higher MDA levels. Carpenters are exposed to elevated levels of wood dust and noise, leading to oxidative stress, which increases their susceptibility to sleep disorders and insomnia.

BACKGROUND: To compare the adding effect of virtual reality exercises (VRE) versus high volume resistance training (HVRT) to low calorie diet (LCD) on blood biomarkers and body fat in obese adult females.

METHODS: Sixty sedentary obese females (aged 40-60 years; BMI 30-40 kg/m) were randomly assigned to three groups: VRE plus LCD, HVRT and LCD, or LCD only. Both exercise interventions were conducted three times weekly for 12 weeks. The outcome measures were lipid profile, glycated hemoglobin (Hb A1C), C-reactive protein (CRP), percentage of body fat (PBF), trunk fat (TF), waist hip ratio (WHR), skinfold thickness (SFT), quality of life (QOL), and fatigue severity (FS). All measurements were taken at baseline and after twelve weeks. Data were analyzed using mixed-model MANOVA with Bonferroni post-hoc tests (α < 0.05).

RESULTS: Significant multivariate effects were found for group, time, and group-time interaction (p < 0.001). Both VRE and HVRT groups demonstrated significant reductions in total cholesterol, triglycerides, LDL, HbA1c, CRP, PBF, TF, WHR, and skinfold thickness, with increased HDL and improved QOL and FS (p < 0.01). No significant differences were observed between VRE and HVRT groups (p > 0.05), whereas both were superior to LCD alone across all outcomes (p < 0.05).

CONCLUSION: Combining VRE or HVRT with a LCD resulted in comparable improvements on lipid profile, HbA1c, CRP, PBF, TF, WHR, SFT, QOL, and FS, exceeding the benefits of dietary intervention alone. Virtual reality exercise may offer an engaging alternative to traditional resistance training for obesity management in women.

Cyclin-dependent kinase 2 (CDK2) and vascular endothelial growth factor receptor 2 (VEGFR2) are essential for the development of tumor angiogenesis and the cell cycle, respectively. Inhibiting both kinases at the same time has therefore become a sensible anticancer tactic. A number of unique hybrid compounds containing isatin-triazole and isatin-imidazole scaffolds were created and thoroughly described in an effort to find dual CDK2/VEGFR2 inhibitors. Compounds 5d, 5k, and 10 showed the strongest antiproliferative activity against breast (MCF7) and prostate (PC3) cancer cell lines among the produced derivatives. Notably, compound 10 showed the most inhibitory potency, with IC values of 0.058 μM for VEGFR2 and 0.789 μM for CDK2, respectively. These values are on par with or higher than those of the reference standards, roscovitine and sunitinib. Additionally, a biological study showed that compounds 5d and 5 k had negligible off-target toxicity and were selectively lethal to cancer cells compared to normal HaCaT keratinocytes. Furthermore, cell cycle studies revealed that compound 5d produced S-phase arrest, whereas compounds 5 k and 10 mostly caused G-phase arrest, in line with their kinase inhibition profiles. Additionally, the potent analogues 5d and 10 substantially decreased colony formation and tumoral cell migration. Molecular docking and dynamics simulations helped to clarify the possible binding interactions inside the ATP-binding sites of CDK2 and VEGFR2, confirming the dual-binding mechanism that underlies their potent effects. According to all of these findings, compound 10 is a potential dual CDK2/VEGFR2 inhibitor that offers a helpful foundation for the development and optimization of future multitarget anticancer agents.

BACKGROUND & AIMS: Noninvasive tests (NITs) are widely used to risk-stratify patients with metabolic dysfunction-associated steatotic liver disease (MASLD); however, their performance may vary according to patient characteristics. We evaluated the accuracy of NITs in a large, multinational MASLD cohort across select subpopulations.

METHODS: We analyzed 18,759 adults with biopsy-confirmed MASLD from 41 countries. NITs included FIB-4, liver stiffness measurement (LSM), and Agile-3+. Diagnostic performance for advanced fibrosis (F3-F4) was measured using areas under the curve (AUCs) across subgroups defined by age, sex, type 2 diabetes (T2D), obesity, and alcohol use. Subgroup-specific cutoffs were derived.

RESULTS: Advanced fibrosis was present in 37% of patients. Pooled AUCs were 0.79 for FIB-4, 0.83 for LSM, and 0.86 for Agile-3+. FIB-4 accuracy declined with age (AUC 0.70 in ≥65 years vs 0.79 in <65 years, P<.0001) and in middle-aged patients with T2D. The LSM performance remained stable across T2D status but was moderately reduced in patients with obesity and, more profoundly, morbid obesity (body mass index [BMI] >35 kg/m). Sex and alcohol use had minimal impact on AUCs. Age- and T2D-specific FIB-4 cutoffs varied substantially to maintain predefined accuracy (sensitivity or specificity). The cutoffs for LSM also differed based on patients' BMI, with lower diagnostic cutoffs for advanced fibrosis required in nonobese MASLD (sensitivity 80%: 8.8 kPa in lean, 9.0 kPa overweight, 9.6 kPa in obesity, 11.0 kPa in morbid obesity).

CONCLUSIONS: Accuracy of NITs for advanced fibrosis in MASLD is influenced by age, T2D, and obesity. Age-adjusted FIB-4 thresholds may enhance risk stratification. Imaging-based and composite NITs (LSM and Agile-3+) provide more consistent performance across MASLD subpopulations.

Dental disorders, such as cavities, periodontal disease, and periapical infections, remain major global health issues, often resulting in pain, tooth loss, and systemic complications if not identified early. Traditional diagnostic methods rely heavily on visual inspection and manual interpretation of panoramic X-ray images by dental professionals, making them time-consuming, subjective, and less accessible in resource-limited settings. : Accurate and timely diagnosis is vital for effective treatment and prevention of disease progression, reducing healthcare costs and patient discomfort. Recent advances in deep learning (DL) have demonstrated remarkable potential to automate and improve the precision of dental diagnostics by objectively analyzing panoramic, periapical, and bitewing X-rays. In this research, a hybrid feature-fusion framework is proposed. It integrates handcrafted Histogram of Oriented Gradients (HOG) features with deep representations from DenseNet-201 and the Shifted Window (Swin) Transformer models. Sequential dependencies among the fused features were learned utilizing the Long Short-Term Memory (LSTM) classifier. The framework was evaluated on the Dental Radiography Analysis and Diagnosis (DRAD) dataset following preprocessing steps, including resizing, normalization, Contrast Limited Adaptive Histogram Equalization (CLAHE) enhancement, and image cropping. : The proposed LSTM-based hybrid model achieved 96.47% accuracy, 91.76% specificity, 94.92% precision, 91.76% recall, and 93.14% F1-score. : The proposed framework offers flexibility, interpretability, and strong empirical performance, making it suitable for various image-based recognition applications and serving as a reproducible framework for future research on hybrid feature fusion and sequence-based classification.

Isolation of beneficial probiotics from traditional foods is a priority in functional food research. We isolated and characterized a lactic acid bacteria (LAB) probiotic strain from Egyptian cuisine, with therapeutic applications for alleviating the manifestations of metabolic syndrome (MetS), including hyperglycemia, hypercholesterolemia and obesity. LAB (n = 10) were isolated from 12 food and juice samples, identified and assessed in vitro for glucose- and cholesterol-lowering capabilities. The most promising isolate underwent probiotic characterization, including gastrointestinal tolerance, surface hydrophobicity, auto-aggregation, and milk fermentation capacity. Other beneficial properties, such as exopolysaccharide production and antimicrobial activity, were also tested. The selected isolate was evaluated for a hypoglycemic and hypocholesterolemic effect using a high-fat diet/streptozotocin-induced hypercholesterolemia and diabetes model in Wistar rats. Lactiplantibacillus plantarum Y, isolated from Egyptian cottage cheese, reduced glucose and cholesterol levels in vitro by 53 ± 0.47% and 98 ± 0.18%. It showed good probiotic characteristics: minimal viability loss in simulated gastrointestinal conditions (0.07 and 0.08 log CFU/mL), good hydrophobicity (> 70%), high auto-aggregation (82.6 ± 0.86% after 24 h), positive exopolysaccharide production, milk fermentation capability with 21-day storage stability, and an antimicrobial activity against Staphylococcus aureus ATCC 25923, Salmonella enterica ATCC 14028, Klebsiella pneumoniae ATCC 10031, and Escherichia coli ATCC 25922. In vivo administration of L. plantarum Y in a MetS rat model resulted in significant hypoglycemic, hypocholesterolemic, and anti-obesity effects. In conclusion, L. plantarum Y is a promising probiotic for managing MetS manifestations. Further clinical investigations for use as a therapeutic intervention are highly recommended.

Accurate classification of cancer subtypes is crucial for personalised therapies and targeted interventions. In this study, we propose BioGAT-LGG, a deep learning framework that integrates multi-omics data, including mRNA, miRNA, and DNA methylation, using a correlation-based Graph Attention Network version 2 (GATv2) for biomarker discovery and Lower-Grade Glioma (LGG) subtype classification. Unlike existing methodologies that rely on external biological priors, such as protein-protein interaction networks or reference graphs, BioGAT-LGG constructs gene-driven correlation graphs, enabling the model to learn biologically meaningful molecular interactions. To improve feature interpretability and reduce dimensionality, LASSO regression is performed during model training. The model achieved 98.03% accuracy, with precision (98.12%), recall (97.74%), and F1-score (97.87%) in a stratified 10-fold cross-validation. Extensive analysis and enrichment of known cancer-related pathways, including PI3K-Akt signalling, Small Cell Lung Cancer, and Transcriptional Misregulation in Cancer, identified the biomarkers hsa-mir-3936, MTCO1P40, and CCND2, which were subsequently validated. These results indicate that BioGAT-LGG effectively captures biologically validated mechanisms and can enable clinically significant subtype classification and biomarker-guided decision-making. This framework thus lays a scalable foundation for multi-omics integration in oncology, which can be further adopted in other tumour types.

Astrogliosis is thought to be a potential factor in the neuroinflammatory response associated with fibromyalgia (FM); however, the role of A1/A2 astrocyte polarization remains underexplored. Several metabolic processes have been reported to influence astrocyte activation and function. The current study was designed to assess the potential regulatory role of apigenin (API), a natural flavonoid, on astrocytes polarization via modulation of the kynurenine pathway (KP) in rats with FM-like symptoms. Reserpine (Res) (1 mg/kg/day, s.c.) was injected into the rats for three consecutive days to induce FM, after which they were given oral API (25 mg/kg/day) for 14 days. API ameliorated spinal cord degeneration as well as allodynia and hyperalgesia as demonstrated in the Randall-Selitto, Von Frey, and hot plate tests. It restored monoaminergic balance and reduced the contents of glutamate and substance P. API suppressed aryl hydrocarbon receptors (AHR), kynurenine (KYN), indoleamine 2,3-dioxygenase (IDO), and nuclear factor kappa B (NF-κB) overexpression in the spinal cord. API hampered astrogliosis as evidenced by reduced GFAP immunohistochemical expression and its associated neuroinflammation and oxidative stress. Consequently, it inhibited A1 astrocytes polarization as evidenced by diminished their markers, namely C3, C1q, and S100β, contrary to upleveling S100A10, an A2 phenotype's marker. In conclusion, API mitigated FM-like pain symptoms by driving astrocyte polarization towards the neuroprotective A2 through modulating the KYN/AHR axis and its interaction with NF-κB signaling.

Astrogliosis is thought to be a potential factor in the neuroinflammatory response associated with fibromyalgia (FM); however, the role of A1/A2 astrocyte polarization remains underexplored. Several metabolic processes have been reported to influence astrocyte activation and function. The current study was designed to assess the potential regulatory role of apigenin (API), a natural flavonoid, on astrocytes polarization via modulation of the kynurenine pathway (KP) in rats with FM-like symptoms. Reserpine (Res) (1 mg/kg/day, s.c.) was injected into the rats for three consecutive days to induce FM, after which they were given oral API (25 mg/kg/day) for 14 days. API ameliorated spinal cord degeneration as well as allodynia and hyperalgesia as demonstrated in the Randall-Selitto, Von Frey, and hot plate tests. It restored monoaminergic balance and reduced the contents of glutamate and substance P. API suppressed aryl hydrocarbon receptors (AHR), kynurenine (KYN), indoleamine 2,3-dioxygenase (IDO), and nuclear factor kappa B (NF-κB) overexpression in the spinal cord. API hampered astrogliosis as evidenced by reduced GFAP immunohistochemical expression and its associated neuroinflammation and oxidative stress. Consequently, it inhibited A1 astrocytes polarization as evidenced by diminished their markers, namely C3, C1q, and S100β, contrary to upleveling S100A10, an A2 phenotype's marker. In conclusion, API mitigated FM-like pain symptoms by driving astrocyte polarization towards the neuroprotective A2 through modulating the KYN/AHR axis and its interaction with NF-κB signaling.

Lipopolysaccharide (LPS) in follicular fluid impairs steroid production and oocyte developmental competence in cows and mice. This study assessed LPS concentrations in equine follicular fluid and their association with steroid and some cytokine levels. Additionally, we evaluated whether LPS exposure during in vitro maturation (IVM) affects equine oocyte developmental competence. In experiment 1, follicular fluid from large follicles (>30 mm in diameter) was collected from 16 slaughterhouse mares, and concentrations of LPS, estradiol, progesterone, TNF-α, and IL-6 were measured. In experiment 2, cumulus-oocyte complexes (COCs) were held overnight, then matured in vitro with (1 ng LPS/1 mL; LPS group) or without LPS (control group), and mature oocytes (n = 47 and 45, respectively) were fertilized using ICSI. Follicular fluid concentrations of LPS ranged between 5.21 and 12.08 endotoxin unit (EU)/mL (10 EU = 1 ng) and were negatively correlated with progesterone, IL-6, and TNF-α levels. Compared to controls, LPS exposure during IVM did not significantly affect maturation (56 % vs. 61 %; P = 0.432), cleavage (71 % vs. 65 %; P = 0.873), or blastocyst rates (21 % vs. 19 %; P = 0.227). In conclusion, this is the first report detecting LPS in the follicular fluid of clinically healthy mares and showing its negative association with progesterone, IL-6, and TNF-α. Exposing equine COCs to 1 ng/mL LPS during in vitro maturation had no significant effect on blastocyst rates. However, further research is needed to determine whether blastocysts derived from oocytes matured under LPS exposure can establish pregnancy after transfer.

OBJECTIVES: To culturally adapt the Arabic version of the Exercise Adherence Rating Scale (EARS) and evaluate its psychometric properties in chronic low back pain patients (CLBP).

METHODS: This methodological study cross-culturally adapted EARS into Arabic (EARS-Ar) following recommended guidelines. Ninety-three CLBP outpatients were prescribed home-based exercises. Dimensionality of the EARS-Ar was assessed by Confirmatory Factor Analysis (CFA) and validity was assessed by comparing EARS-Ar with Fear-Avoidance Beliefs Questionnaire (FABQ), Numeric Pain Rating Scale (NPRS), and Roland Morris Disability Questionnaire (RMDQ). Internal consistency and test-retest reliability were evaluated. Responsiveness was examined using the receiver operating characteristic curve (AUC).

RESULTS: CFA confirmed dimensionality of the EARS-Ar. It had moderate negative correlations (rho= -0.42 to -0.62) with FABQ, NPRS, and RMDQ. EARS-Ar demonstrated excellent internal consistency ( = 0.97). Intraclass correlation coefficients were excellent (ICCs= 0.89-0.920) with acceptable corrected item correlations (rho= 0.56-0.77). Responsiveness of the EARs-Ar was good with significant moderate correlation (rho= 0.35) between the EARS-Ar change score and global rating of change (GRoC). A cutoff point of 12.5/24 was determined with moderate accuracy (AUC= 0.81, sensitivity= 81%, specificity= 41%).

CONCLUSIONS: EARS-Ar showed good reliability, validity, and responsiveness, which renders it a reliable tool for evaluating exercise adherence behavior of CLBP patients.