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We describe the design and synthesis of two isatin-tethered quinolines series (Q6a–h and Q8a–h), in connection with our research interest in developing novel isatin-bearing anti-tubercular candidates. In a previous study, a series of small molecules bearing a quinoline-3-carbohydrazone moiety was developed as anti-tubercular agents, and compound IV disclosed the highest potency with MIC value equal to 6.24 µg/mL. In the current work, we adopted the bioisosteric replacement approach to replace the 3,4,5-trimethoxy-benzylidene moiety in the lead compound IV with the isatin motif, a privileged scaffold in the TB drug discovery, to furnish the first series of target molecules Q6a–h. Thereafter, the isatin motif was N-substituted with either a methyl or benzyl group to furnish the second series Q8a–h. All of the designed quinoilne-isatin conjugates Q6a–h and Q8a–h were synthesized and then biologically assessed for anti-tubercular actions towards drug-susceptible, MDR, and XDR strains. Superiorly, the N-benzyl-bearing compound Q8b possessed the best activities against the examined M. tuberculosis strains with MICs equal 0.06, 0.24, and 1.95 µg/mL, respectively.

Opuntia ficus-indica (L.) Mill. has been used in folk medicine against several diseases. The objectives of the present study were to investigate the chemical composition of the methanolic extract of O . ficus-indica (L.) Mill. flowers and their antioxidant, antimicrobial, and anticancer properties. Besides, network pharmacology and molecular docking were used to explore the potential antitumor effect of active metabolites of O . ficus-indica (L.) Mill. against breast and liver cancer. The results revealed many bioactive components known for their antimicrobial and anticancer properties. Furthermore, scavenging activity was obtained, which indicated strong antioxidant properties. The plant extract exhibited antimicrobial activities against Aspergillus brasiliensis (MIC of 0.625 mg/mL), Candida albicans , Saccharomyces cerevisiae , Staphylococcus aureus , Escherichia coli , and Pseudomonas aeruginosa at MICs of 1.25 mg/mL. The results revealed proapoptotic activities of the O . ficus-indica (L.) Mill. extract against MCF7, MDA-MB-231, and HepG2 cell lines, where it induced significant early apoptosis and cell cycle arrest at sub-G1 phases, besides increasing the expression levels of p53, cyclin D1, and caspase 3 ( p <0.005). The network pharmacology and molecular docking analysis revealed that the anticancer components of O . ficus-indica (L.) Mill. flower extract targets the PI3K-Akt pathway. More investigations might be required to test the mechanistic pathways by which O . ficus-indica (L.) Mill. might exhibit its biological activities in vivo .

Objective: This study aims to develop an intranasal (IN) delivery system for glioblastoma multiforme (GBM) management using repurposed superparamagnetic iron-oxide (SPION) loaded with atorvastatin (ATO)-nanostructured lipid carrier (NLC). Methods: Emulsification and ultrasonication were used to formulate ATO-NLCs, and the best formula was loaded with SPION to make the final atorvastatin/superparamagnetic iron oxide-loaded nanostructured lipid carrier (ASN) formulation. Entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), and drug release after 6 h (Q6h) were evaluated for NLCs. ASN was tested for cytotoxicity on T98G cancer cells, and the cell cycle was examined to determine cell death. Furthermore, the ability of the optimal formulation to suppress the levels of inflammatory biomarkers was investigated in Lipopolysaccharide (LPS)-induced inflammation. The brain-targeting behavior of IN-ASN was visualized in rabbits via confocal laser scanning microscopy (CLSM). Results: The optimum NLC exhibited a spherical shape, EE% of 84.0 ± 0.67%, PS of 282.50 ± 0.51 nm, ZP of −18.40 ± 0.15 mV, and Q6h of 89.23%. The cytotoxicity of ASN against cancer cells was 4.4-fold higher than ATO suspension, with a 1.3-fold increment in cell apoptosis. ASN showed significantly reduced pro-inflammatory biomarkers (IL-β, IL-6, TNF-α, TLR4, NF-қB), whereas CLSM revealed enhanced brain delivery with no observed histopathological nasal irritation. The in silico analysis demonstrated enhanced ATO-ADME (absorption, distribution, metabolism, and excretion) properties, while the network pharmacology study identified 10 target GBM genes, among which MAPK3 was the most prominent with a good binding score as elucidated by the simulated docking study. Conclusions: These findings may present ATO/SPION-NLCs as significant evidence for repurposing atorvastatin in the treatment of glioblastoma multiforme.

The SARS-CoV-2 pandemic at the end of 2019 had major worldwide health and economic consequences. Until effective vaccination approaches were created, the healthcare sectors endured a shortage of operative treatments that might prevent the infection’s spread. As a result, academia and the pharmaceutical industry prioritized the development of SARS-CoV2 antiviral medication. Pyranopyrazoles have been shown to play a prominent function in pharmaceutical chemistry and drug sighting because of their significant bioactive properties. We provide herein a novel sequence of pyranopyrazoles and their annulated systems whose antiviral efficacy and cytotoxicity were explored versus human coronavirus 229E (HCoV-229E) Vero-E6 cell lines as a model for the Coronaviridae family. Fifteen synthetic congeners pointed out miscellaneous antiviral efficacies against HCoV-229E with variable inhibition degrees. Compound 18 showed a high selectivity index (SI = 12.6) that established spectacular inhibitory capacity against human coronavirus 229E. Compounds 6, 7, and 14 exposed moderate efficacies. Compounds 6, 7, 14, and 18 exhibited substantial antiviral action through the replication phase with reduction percentages extending from 53.6%, 60.7%, and 55% to 82.2%, correspondingly. Likewise, when assessed to the positive control tipranavir (88.6%), the inhibitory efficiency of compounds 6, 7, 14, and 18 versus the SARS-CoV2 Mpro provided high percentages of 80.4%, 73.1%, 81.4% and up to 84.5%, respectively. In silico studies were performed to investigate further the biological activity and the target compounds’ physical and chemical features, including molecular dynamic (MD) simulations, protein–ligand docking, ADME studies, and density functional theory (DFT) calculations. These inquiries demonstrated that this series of metabolically stable pyranopyrazoles and their annulated systems are effective human coronavirus inhibitors that inhibit the viral Mpro protein and may have emerged as a novel COVID-19 curative option.

Background: Nephrolepis exaltata (sword fern) possesses a considerable amount of phytochemicals and different biological activities. The current study investigates the anti-biofilm potential of greenly synthesized bimetallic nanoparticles of Nephrolepis exaltata leaf methanol extract (NEME-MnO2-MgO BNPs). Methods: The NEME was subjected to UPLC/MS analysis, followed by characterization of its NPs by size, zeta potential, FTIR, entrapment efficiency, and release. Then, antioxidant, antimicrobial and antibiofilm assays were employed, followed by in silico studies. Results: The UPLC/MS analysis of NEME led to the tentative identification of 27 metabolites, mostly phenolics. The MnO2-MgO BNPs presented a uniform size and distribution and exhibited IC50 values of 350 and 215.6 μg/mL, in the DPPH and ABTS assays, respectively. Moreover, the NPs exhibited antimicrobial and anti-biofilm efficacies against Pseudomonas aeruginosa, Klebsiella pneumonia (ATCC-9633), Staphylococcus aureus (ATCC-6538), Escherichia coli, Bacillus cereus, and C. albicans, with MIC values of 250–500 μg/mL. The MnO2-MgO BNPs inhibited Candida albicans biofilms with a % inhibition of 66.83 ± 2.45% at 1/2 MIC. The network pharmacology highlighted epigallocatechin and hyperoside to be the major compounds responsible for the anti-biofilm potential. The ASKCOS facilitated the prediction of the redox transformations that occurred in the green synthesis, while the docking analysis revealed enhanced binding affinities of the oxidized forms of both compounds towards the outer membrane porin OprD of P. aeruginosa, with binding scores of −4.6547 and −5.7701 kcal/mol., respectively. Conclusions: The greenly synthesized Nephrolepis exaltata bimetallic nanoparticles may provide a promising, eco-friendly, and sustainable source for antimicrobial agents of natural origin with potential biofilm inhibition.

Inclusive educational practices enhance engagement among students with disabilities in school settings. This study aimed to investigate: (i) the general attitudes of non-disabled female Saudi Arabian students toward their peers with disabilities, with a particular focus on the general attitudes towards those with hearing disabilities (HD), intellectual disabilities (ID), and behavioral problems (BP), and (ii) the relationships between three selected student-related characteristics (type of school, in-school contact with peers with disabilities, and out-of-school contact with peers with disabilities). Using a sample of 678 participants aged 7-12 years old, we tested the impact of personal and contextual factors (age, type of peer disability, type of school, in-school interaction with peers with disabilities, and out-of-school interaction with peers with disabilities on the attitudes of non-disabled Saudi Arabian elementary school students using ANCOVA linear regression analysis. Regardless of the type of disability, the participants reported having positive attitudes toward peers with disabilities. The type of disability, school, and previous interactions all had a significant effect on fostering positive attitudes toward peers with disabilities, specifically, those with HD, ID, and BP. The participants had less positive attitudes towards their peers with BP compared to their attitudes towards peers students with HD or ID which were more positive and had a larger effect size. The findings also demonstrated that the participants' attitudes toward their peers with HD or ID were influenced by their previous experience of interacting with people with disabilities as well as the type of school they attended. Participants from Saudi ARAMCO (SA) schools had more positive attitudes toward peers with disabilities compared to those from public schools, and participants from non-inclusive schools had more positive attitudes toward peers with disabilities compared to those from inclusive schools. Participants from non-inclusive schools had much more positive attitudes toward peers with disabilities than those from inclusive schools; participants who had previous out-of-school interactions with people with disabilities had significantly more positive attitudes toward peers with disabilities than those who had no previous out-of-school interactions with people with disabilities. Participants from SA schools had the most negative attitudes toward peers with BP, regardless of age. The findings imply that being taught in an inclusive educational setting in Saudi Arabia does not inevitably encourage non-disabled students to adopt more positive attitudes toward peers with disabilities. Therefore, with the support of their school principals, Saudi Arabian teachers working in inclusive educational settings should be encouraged to develop and implement initiatives to adopt an inclusive strategy based on group projects bringing together students with and without disabilities.

Cerebral palsy (CP) is the most common childhood disability, affecting 1.5–3 per 1000 live births. Physical exercises have been shown to improve muscle and limb outcomes in CP. This systematic review critically appraises existing systematic reviews on the effects of physical activity and exercise on physical, functional, and psychosocial outcomes in individuals with CP compared to those without. Using a PICO framework, the question was: In patients with CP, do physical activity and exercise improve muscle- and limb-related outcomes compared to no intervention or usual care? PubMed, Cochrane, ISI Web of Science, and Embase were searched for systematic reviews meeting inclusion criteria. Seven reviews focusing on exercise-related outcomes in CP were synthesized. Exergaming significantly improved fine motor dexterity (SMD = 3.12) but not gross manual dexterity. Progressive resistance and general physical activity increased muscle strength (SMD = 0.59), while aerobic exercise showed mixed results. Task-oriented training led to large improvements in gross motor function (SMD = 6.04–11.05) and functional independence (SMD = 6.44). VR-based and aerobic interventions had modest or nonsignificant effects on mobility, balance, and walking. Adverse events were infrequently reported and generally mild. Task-oriented and VR-assisted training showed the most consistent benefits, though heterogeneity and incomplete reporting limit conclusions. Physical exercises, particularly task-oriented and VR-assisted training, improve motor and limb functions in CP. Future research with longer follow-up, larger samples, and better safety reporting is needed to confirm clinical impact. The King Salman Center for Disability Research, Grant/Award Number: KSRG-2024–036. PROSPERO registration number: CRD42025646412. •Physical activity and exercise interventions improve motor outcomes and physical fitness in individuals with cerebral palsy.•Intervention effects vary across reviews due to differences in populations, intervention types, and outcomes.•Further research is needed to address limited long-term follow-up and underreporting of adverse outcomes.

Background and Objectives: Life satisfaction (LS) is a key aspect of mental well-being, particularly for individuals with physical disabilities (IWPDs).This study examined LS levels among IWPDs in Saudi Arabia, focusing on the effects of three independent variables: (i) sociodemographic factors, (ii) self-reported health and fitness, and (iii) self-assessed physical activity (PA). Materials and Methods: Data was collected from 271 participants using validated questionnaires. Two models analyzed the effects of the independent variables on LS: the first model included the overall level of PA, while the second examined its individual components. Results: The results indicated that females reported a higher LS than males (p = 0.011). Participants with a university degree demonstrated a significantly greater LS compared to those who did not disclose their educational status (Exp(β) = 1.104). Poor health and inactivity were linked to a lower LS, while age correlated positively with LS (odds ratio = 1.012). Additional factors, including marital status, income, education level, and mobility assistance usage, significantly impacted LS. Interestingly, PA exhibited no direct statistical effect on LS. Conclusions: These findings highlight the importance of equitable access to education, regular PA, support for married couples, and preventive healthcare. Special attention to young people, particularly boys, is recommended to improve LS outcomes among IWPDs in Saudi Arabia.

Background/Objectives: Predicting diseases based on the gut microbiome pattern is still difficult because of compositional shortcomings, batch heterogeneity, and scanty modeling of inter-taxon interactions. This study introduces a Dysbiosis-Aware Multiset Transformer Framework called DysbioFormer, which predicts state diseases by recognizing patterns of microbes. Methods: The current methods are mainly based on flat abundance representations or fixed-order models which limit the capability of describing intricate interactions of communities and evolutionary structure. Results: DysbioFormer is a solution to these shortcomings, in which each sample of the microbiome is modeled as a permutation-invariant multiset of taxonomic tokens with compositional, phylogenetic, and harmonized cohort data. Stacked Set Attention Blocks are used to learn relational dependencies between taxa, whereas Pooling-by-Multihead-Attention is used to aggregate global disease-level embeddings and this is not based on sequence assumptions. The model has been tested on MicrobiomeHD, which consists of a wide variety of human gut microbiome samples at a variety of disease conditions and healthy controls. Experimental results demonstrate strong diagnostic performance, achieving an accuracy of 97%, an AUC of 0.97, and an F1-score of 96%, consistently outperforming classical machine learning models under identical evaluation protocols. Attention-derived signatures also can give interpretable connections among predictive results and disease-linked microbial taxa, enhancing biological plausibility. Conclusions: The suggested architecture enables scalable, cohort-agnostic microbial diagnostics, and provides a principled route to transforming the complex information of the microbiome into reliable clinical information. DysbioFormer creates a universal basis of future microbiome-based disease screening and precision health uses. Its design allows extending towards multi-omics integration, longitudinal studies, and decision-support infrastructure, supporting microbiome-informed translational medicine in a variety of clinical research settings.