Cancer is a complex disease characterized by uncontrolled cell proliferation, often driven by dysregulated cyclin-dependent kinases (CDKs), particularly CDK2, which plays a crucial role in cell cycle progression. Aberrant CDK2 activity is associated with tumor growth and resistance to therapy, making CDK2 a promising therapeutic target. The main focus of this research is to integrate the multi-omics-based pan-cancer analysis of CDK2 to identify novel plant-derived inhibitors, bridging the prognostic and therapeutic relevance of CDK2 across various cancer types. In this study, to evaluate CDK2's expression, prognostic behavior, genetic alterations, and immune infiltrations, we performed pan-cancer analysis. The oncogenic analysis showed that CDK2 is significantly overexpressed in multiple tumor types and, in some cancers, which correlated with poor overall and disease-free survival, indicating its potential as a context-dependent prognostic biomarker. The involvement of CDK2 in key cell cycle and oncogenic pathways was investigated, highlighting its centrality in tumor proliferation networks. Additionally, cheminformatics and machine learning approaches were applied to screen phytocompounds from six medicinal plants, and the top phytocompounds (>pIC₅₀ = 5.1) were then subjected to molecular docking, pharmacodynamics, pharmacokinetics, and dynamics simulation studies. Docking results revealed that withanolide M, withanolide K, and ergosterol showed the highest binding affinities against CDK2, with scores of −10.2, −10.1, and −9.9 kcal mol⁻¹, respectively. These lead phytocompounds exhibited high potency, excellent pharmacokinetic properties, and minimal predicted toxicity as compared with the control inhibitor of CDK2. The binding stability of the protein–ligand complexes was confirmed by dynamic simulations along with MM-GBSA calculations, with the results supporting our previously reported affinity score. Therefore, these phytocompounds could be potential CDK2 inhibitors, warranting exploration in future cancer research. Furthermore, additional experimental and clinical validations are required to confirm the efficacy and efficiency of these potential lead compounds.

Microplastics (MPs) are increasingly detected environmental contaminants in both marine and freshwater ecosystems, with reported concentrations ranging from a few to thousands of particles per cubic meter depending on location and methodology. Although growing evidence suggests potential risks to aquatic organisms, the extent of their ecological and biological impacts is still under active investigation. Their size, persistence and capacity to transport chemical additives and co-contaminants allow them to enter biological systems by ingestion and respiration. When ingested, MPs cause oxidative stress, inflammation, and metabolic disorders, resulting in the destruction of vital tissues in major body organs including liver, gills, intestines, and brain. They also change gene expression, cause endocrine and immune pathway perturbation, induce apoptosis, and cause gut microbiome dysbiosis, all of which worsen the health and survival of the organism. MPs also serve as vectors of heavy metals, antibiotics, pesticides, and pathogens and enhance toxicity due to the Trojan horse effect and enable bioaccumulation in food webs. Due to their widespread presence in water, soil, air, and food, MP pollution has direct effects on human, animal, and ecosystem health. This review synthesizes current knowledge on the sources of MPs, the mode of exposure, and the mechanism of toxicity and new ecological implications. It also presents mitigation measures, and stresses a One Health paradigm as the key to taking concerted action on the international level to minimize MP pollution and protect both the environment and human health.

The rapid growth in plastic production and consumption has led to the widespread contamination of the environment with microplastics (MPs), raising increasing concerns about their potential impacts on human health. In recent years, advances in analytical techniques have revealed the presence of MPs in a wide range of human biological samples, suggesting that these particles can enter, circulate within, and accumulate throughout the human body. This narrative review provides a comprehensive overview of the current evidence on the occurrence and distribution of MPs in human tissues, organs, and biological fluids. MPs have been detected in blood, urine, stool, semen, breast milk, amniotic fluid, ocular fluids, and lavage fluids, as well as in several organs and tissues including the lungs, placenta, heart, kidneys, liver, vascular tissues, and reproductive organs. Among the identified polymers, polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET), polystyrene (PS), and polyvinyl chloride (PVC) are reported most frequently. This narrative review also summarizes the major analytical techniques used for MP detection and characterization, including Raman spectroscopy, μ-FTIR, LDIR spectroscopy, and Py-GC/MS, which highlight their advantages and limitations. Collectively, the available evidence demonstrates that MPs are not confined to the external environment but are now detectable in multiple compartments of the human body, including highly protected biological systems. However, important questions remain regarding their long-term persistence, transport mechanisms, biological fate, and potential health effects. Further methodological standardization and large-scale human studies are needed to better understand the extent of human exposure and the implications of MP accumulation for human health.

Transcriptomics and machine learning approaches spotlight natural compounds as CDK1 blockers.

Cancer is characterized as a multifactorial disease due to their complex genetic and molecular mechanisms that often converge across tissue types. Shared oncogenic pathways can help us understand these functions and discover broad-spectrum therapeutics. Earlier, most studies focused on finding specific drivers for individual cancer types. However, researchers are now more interested in identifying common molecular patterns across different cancers and developing therapies that can target multiple pathways at once. This study aimed to understand the common oncogenic pathways between breast, ovarian and colorectal (BOC) cancers and identify possible multitargeted therapeutic drug molecules. To identify the common differentially expressed genes (DEGs), we analyzed three transcriptomic datasets and found a total of 128 DEGs. The protein-protein interaction (PPI) network study reveals the top-ranked, most significant hub targets, AURKA, CDK1 and CCNB1, as drug targets. Enrichment analysis with GO and KEGG pathways, as well as regulatory network (TFs and mRNAs) analysis, revealed common pathogenetic processes among BOC cancers. The AMG-900 exhibits the highest binding affinity scores of −10.8, −9.40, and −9.7 kcal/mol with the target proteins AURKA, CCNB1, and CDK1, respectively. The stability and structural flexibility of the selected protein-ligand complexes were validated by a large-scale (500 ns) molecular dynamics and MM-GBSA analyses, and the results indicate stable interactions for AURKA and CCNB1, while CDK1 showed comparatively reduced stability. The pharmacokinetic analysis revealed favorable drug-likeness and a manageable toxicity profile typical of anticancer agents. Therefore, the findings of this study propose that AMG-900 may serve as a promising multi-targeted candidate for further investigation in multi-target therapeutic strategies within precision oncology. Furthermore, these results require additional experimental (in vivo and in vitro) and clinical validation to confirm the potentiality and efficiency of this (AMG-900) lead compound.