Background/Objective: Antimicrobial resistance (AMR) and therapy-resistant cancer cells represent major clinical challenges, necessitating the development of novel therapeutic strategies. This study explores the use of selenium nanoparticles (SeNPs) and colistin-conjugated selenium nanoparticles (Col-SeNPs) as a dual-function nanotherapeutic against multidrug-resistant Pseudomonas aeruginosa, antifungal-drug-resistant Candida spp., and human breast carcinoma (MCF-7) cells. Methods: SeNPs were synthesized and characterized using UV-Vis spectroscopy, atomic force microscopy (AFM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FTIR), confirming their nanoscale morphology, purity, and stability. Results: The antimicrobial activity of SeNPs and Col-SeNPs was assessed based on the minimum inhibitory concentration (MIC) and bacterial viability assays. Col-SeNPs exhibited enhanced antibacterial effects against P. aeruginosa, along with significant downregulation of the mexY efflux pump gene, which is associated with colistin resistance. Additionally, Col-SeNPs demonstrated superior antifungal activity against Candida albicans, C. glabrata, and C. krusei compared to SeNPs alone. The anticancer potential of Col-SeNPs was evaluated in MCF-7 cells using the MTT assay, revealing dose-dependent cytotoxicity through apoptosis and oxidative stress pathways. Although MCF-7 is not inherently drug-resistant, this model was used to explore the potential of Col-SeNPs in overcoming resistance mechanisms commonly encountered in cancer therapy. Conclusions: these findings support the promise of Col-SeNPs as a novel approach for addressing both antimicrobial resistance and cancer treatment challenges. Further in vivo studies, including pharmacokinetics and combination therapies, are warranted to advance clinical translation.

Tuberculosis (TB) remains a significant global health concern. Although the Gulf Cooperation Council (GCC) countries have relatively lower TB incidence rates, they face unique challenges, particularly with a large migrant workforce from TB-endemic regions. Understanding trends in TB burden in these countries is essential for guiding public health strategies. We analyzed TB trends in GCC countries from 1990 to 2021 using data from the Global Burden of Disease (GBD) study. Joinpoint regression assessed temporal trends, and ARIMA modeling was used to forecast future TB incidence, mortality, and DALYs. The metrics considered age-standardized mortality rates (ASMR), DALYs rate (ASDR), and incidence rates (ASIR). Data visualizations, including choropleth maps and trend graphs, were also created using R and MS Excel. From 1990-2021, TB incidence, mortality, and DALYs showed a steady decline across the GCC countries. The age-standardized mortality rate (ASMR) decreased by an average annual percentage change (AAPC) of -5.39 %, while the age-standardized DALYs rate (ASDR) decreased at a slightly higher rate of -5.50 %. Forecasting through 2031 predicts a continued decline: the age-standardized incidence rate (ASIR) will fall from 28.4 per 100,000 in 2022-5.4 by 2031, and mortality is expected to decline from 3.87 per 100,000 to 2.39 over the same period. DALYs are projected to decrease from 103.5 in 2022-62 by 2031. Countries like Qatar and Saudi Arabia showed significant improvements, with Qatar achieving a 95.56 % reduction in mortality. However, the UAE with a 61.18 % reduction in incidence and DALYs, showed a 26.71 % increase in mortality. TB control in GCC countries shows positive trends, reflecting successful public health interventions. However, challenges remain, particularly the high prevalence of TB among migrant populations. Continued efforts and tailored interventions are essential to sustain progress toward TB elimination.

In response to the escalating threat of drug-resistant fungi to human health, there is an urgent need for innovative strategies. Our focus is on addressing this challenge by exploring a previously untapped target, yeast casein kinase (Yck2), as a potential space for antifungal development. To identify promising antifungal candidates, we conducted a thorough screening of the diverse-lib drug-like molecule library, comprising 99,288 molecules. Five notable drug-like compounds with diverse-lib IDs 24334243, 24342416, 17516746, 17407455, and 24360740 were selected based on their binding energy scores surpassing 11 Kcal/mol. Our investigation delved into the interaction studies and dynamic stability of these compounds. Remarkably, all selected molecules demonstrated acceptable RMSD values during the 200 ns simulation, indicating their stable nature. Further analysis through Principal Component Analysis (PCA)-based Free Energy Landscape (FEL) revealed minimal energy transitions for most compounds, signifying dynamic stability. Notably, the two compounds exhibited slightly different behaviour in terms of energy transitions. These findings mark a significant breakthrough in the realm of antifungal drugs against C. albicans by targeting the Yck2 protein. However, it is crucial to note that additional experimental validation is imperative to assess the efficacy of these molecules as potential antifungal candidates. This study serves as a promising starting point for further exploration and development in the quest for effective antifungal solutions.Communicated by Ramaswamy H. Sarma.

In mammals, circadian rhythmicity is sustained via a transcriptional/translational feedback loop referred to as the canonical molecular circadian clock. Circadian rhythm is absent in undifferentiated embryonic stem cells; it begins only after differentiation. We used pluripotent P19 embryonal carcinoma stem cells to check the biological clock before and after differentiation into neurons using retinoic acid. We show that the central clock genes ARNTL (Bmal), Per2 and Per3, and the peripheral clock genes Rev-erb-α and ROR-α, oscillate before and after differentiation, as does the expression of the neuronal differentiation markers Hes5, β-3-tubulin (Tubb3) and Stra13, but not Neurod1. Furthermore, the known clock-modulating compounds ERK, EGFR, Pi3K, p38, DNA methylation and Sirtiun inhibitors, in addition to Rev-erb-α ligands, modulate the expression of central and peripheral clock genes. Interestingly Sirtinol, Sirt1 and Sirt2 inhibitors had the greatest significant effect on the expression of clock genes, and increased Hes5 and Tubb3 expression during neuronal differentiation. Our findings reveal a new frontier of circadian clock research in stem cells: contrary to what has been published previously, we have shown the clock to be functional and to oscillate, even in undifferentiated stem cells. Modulating the expression of clock genes using small molecules could affect stem cell differentiation.

Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation and progressive joint dysfunction. Opuntia littoralis (OL) has a high nutritional content and is thought to offer a number of health advantages. We aimed to evaluate the anti-arthritic potential of OL extracts against collagen-induced arthritis (CIA). We designed three OL cladode fractions from the concentrated aqueous extract: hexane, ethyl acetate (EAE), and hydro alcohol (HAE). We investigated the nitric oxide and MDA levels of EAE against lipopolysaccharide-induced RAW264.7 cells; then, we administered EAE to the mice with CIA to confirm the anti-inflammatory effects against RA. HPLC analysis of the OL extracts showed a high concentration of phenolic compounds in EAE. Treatment with EAE (10 and 20 mg/100 g body weight of mice) after 10 days of immunization with collagen showed a significant inhibition of joint inflammation, paw swelling, and edemas. MDA and cytokine levels (IL-1β, IL-6R, IL-6, IL-17, and IL-23) were significantly reduced. EAE effectively ameliorated COX-2, NF-kB, STAT-3, PTEN, and RANKL expression. OL-EAE therapy significantly upregulated the expression of miR-28 and miR-199a. In conclusion, the anti-inflammatory actions of OL-EAE altered the cellular localization of the inflammatory mediators, therefore preventing joint inflammation via partial epigenetic and metabolic regulations in experimental mice.