Search Results (5,564)

Pharmaceutical pollutants have emerged as a critical class of aquatic micropollutants due to their continuous release, persistence, and potential impacts on ecosystems and human health. Conventional wastewater treatment systems are often insufficient to achieve complete removal, necessitating the development of advanced oxidation processes (AOPs), such as Fenton and Fenton-like systems. These processes rely on the generation of reactive oxygen species (ROS), including hydroxyl radicals (•OH), superoxide species, singlet oxygen, and, in some heterogeneous systems, high-valent iron-oxo intermediates, which collectively enable the degradation of structurally diverse and recalcitrant pharmaceutical compounds. Recent advances have highlighted the pivotal role of nanomaterials as catalysts in enhancing Fenton-based processes. Nanostructured catalysts, including iron-based nanoparticles (NPs), metal oxides, carbon-based materials, and bimetallic composites, offer high surface area, tunable redox properties, and improved electron transfer, leading to enhanced catalytic efficiency and mineralization rates. Importantly, the integration of green synthesis approaches using plant extracts, microorganisms, and biopolymers provides environmentally benign routes for nanomaterial fabrication while introducing functional surface groups that improve catalytic performance. Mechanistically, pharmaceutical degradation in Fenton systems involves complex pathways driven by multiple ROS species, including •OH, superoxide radicals, and singlet oxygen, leading to the formation of intermediate products and eventual mineralization. However, challenges such as NP aggregation, metal leaching, incomplete mineralization, and potential toxicity of intermediates remain critical considerations. This review critically evaluates the occurrence of pharmaceutical pollutants, the fundamentals of Fenton and Fenton-like processes, and the design and application of green-synthesized nanomaterials as efficient catalysts. It further explores degradation mechanisms, operational parameters, and sustainability considerations, highlighting future directions for scalable, environmentally responsible water treatment technologies. Full article

Food adulteration is a critical global threat to public health, economic stability, and social welfare. It primarily occurs in two forms: intentional and incidental. Intentional adulteration, or economically motivated adulteration, involves deliberately adding fraudulent or toxic substances such as hazardous ripening agents and harmful coloring to increase profitability. Substitution of food species is also a widely practiced form. Such adulteration can cause severe acute and chronic health issues, ranging from gastrointestinal distress to cancer and organ failure. Incidental adulteration happens through accidental contamination during processing, storage, or distribution, involving hazards such as heavy metals, mycotoxins, and pesticides. Such contaminants also lead to severe chronic diseases and dangerous allergic reactions. Food adulteration also triggers massive socio-economic consequences. Food safety incidents such as the melamine milk crisis and the horsemeat scandal caused billions of dollars in losses due to healthcare costs, product recalls, damaged brand reputation, and disrupted international trade. Global entities such as the WHO, WTO, and Codex Alimentarius have established robust legislative frameworks. However, effective enforcement remains a significant challenge in many countries. To mitigate such harmful impacts, it is essential to strengthen global surveillance systems, enhance rapid analytical detection methods, and strictly enforce compliance with existing food safety regulations. Full article

Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subtype lacking effective targeted therapies. Its tumor microenvironment (TME) exhibits distinct features, including acidity, redox imbalance, elevated reactive oxygen species (ROS), and hypoxia, which provide exploitable triggers for targeted drug delivery. Stimuli-responsive polymeric nanocarriers have emerged as promising platforms that enable spatiotemporally controlled and site-specific therapeutic release in response to these endogenous cues, as well as exogenous stimuli such as temperature and light. These systems improve drug accumulation, penetration, and therapeutic efficacy while reducing systemic toxicity. Unlike previous reviews that broadly discuss nanocarriers in cancer therapy, this review focuses on the structure–function relationships of TME-responsive polymeric systems in TNBC and their translational limitations. We summarize recent advances in pH-, redox-, ROS-, hypoxia-, photo- and temperature-responsive polymers, highlighting their design strategies and therapeutic applications. Key challenges, including stimulus heterogeneity, limited in vivo validation, and clinical translation barriers, are also discussed. This review provides a concise framework for the rational design of programmable, multi-responsive polymeric nanomedicines for TNBC therapy. Full article

Viral infections such as human papillomavirus, rotavirus, and cytomegalovirus continue to pose significant global health challenges, causing persistent and widespread disease. The objective of this study is to evaluate the preliminary in vitro antiviral and cytotoxicity profile of zinc oxide (ZnO) and copper oxide (CuO) nanoparticles, which were synthesized through a green approach using Moringa oleifera leaf extract, against these viruses. Regarding antiviral effects, ZnO nanoparticles demonstrated potent antiviral activity against HPV, CMV, and rotavirus, with high selectivity indices and lower cytotoxicity compared with copper oxide nanoparticles. For HPV and CMV, ZnO showed markedly higher CC₅₀ and SI values (HPV: SI = 10.67; CMV: SI = 10.57) than copper oxide nanoparticles, which exhibited lower selectivity and greater cytotoxicity. Against rotavirus, ZnO nanoparticles also exhibited superior safety and antiviral efficacy (CC₅₀ = 798.42 µg/mL; SI = 11.49), whereas copper oxide nanoparticles showed relatively higher toxicity and lower selectivity. In parallel, quercetin, the major flavonoid of Moringa oleifera, was evaluated in silico as a potential inhibitor of rotavirus VP5*, CMV UL44, and HPV E6 using molecular docking and 150 ns molecular dynamics simulations. Quercetin exhibited favorable binding affinity, stable interaction profiles, and low RMSD fluctuations across all viral targets. Overall, green-synthesized ZnO nanoparticles demonstrated promising preliminary antiviral activity with an improved safety profile compared with CuO nanoparticles, while the computational findings support quercetin as a potential multi-target antiviral candidate. Further studies using direct virological assays and in vivo models are required to validate these findings and elucidate the underlying antiviral mechanisms. Full article

Ubiquitin-related modifier 1 (URM1) defines a distinctive ubiquitin-like system in which URM1 functions both as a covalent protein modifier and a sulfur carrier required for wobble uridine (U34) thiolation of cytosolic tRNAs. This dual role places URM1 signaling at the intersection of protein post-translational modification and codon-sensitive translational control. Although URM1 remains less well characterized than ubiquitin and other ubiquitin-like modifiers, accumulating evidence links URM1-associated processes to oxidative-stress tolerance, proteostasis, and tumorigenesis. In this review, we summarize the molecular architecture and biochemical regulation of URM1 signaling, distinguish the biological significance of protein URMylation from URM1-dependent tRNA U34 thiolation, and evaluate evidence connecting these pathways to cancer biology. Notably, stress-inducible protein URMylation has been demonstrated in mammalian cells, although endogenous mammalian URM1 substrates and their cancer-relevant functions remain incompletely defined to date. In parallel, URM1-dependent tRNA thiolation has been linked to selective translational programs that support metastatic progression and adaptation to targeted therapy. We further discuss emerging therapeutic opportunities associated with redox and translational dependencies, as well as the potential limitations and challenges of pathway selectivity, biomarker development, and normal-tissue toxicity. Together, these studies position URM1 signaling as a context-dependent stress-adaptive network with emerging relevance to cancer biology and precision oncology. Full article

Cardio-oncology has emerged as a critical discipline addressing cardiovascular toxicities from cancer therapies, yet substantial evidence gaps persist for elderly patients, who represent over 60% of new cancer diagnoses. This narrative review synthesizes the current literature on cardio-oncology challenges in older adults (≥65 years), highlighting underrepresentation in clinical trials, compounded risks from frailty, multimorbidity, and polypharmacy, and the paucity of geriatric-specific guidelines. Older adults exhibit heightened susceptibility to cardiotoxicity from antineoplastic therapies due to age-related declines in cardiac reserve and renal function, and baseline atherosclerosis. Comprehensive geriatric assessments (CGA) identify frailty as a key predictor of adverse outcomes, yet their integration into cardio-oncology protocols remains inconsistent, with limited prospective data on risk-stratification tools such as echocardiography and biomarkers. Observational studies underscore disparities in surveillance and management, leading to the undertreatment of cancer and overtreatment of comorbidities. Current cardio-oncology guidelines recognize older age, multimorbidity, frailty, and individualized assessment as important considerations in clinical decision-making. However, validated geriatric-specific thresholds, surveillance strategies, and management algorithms remain limited, particularly for frail older adults and the oldest-old populations. Emerging priorities include multidisciplinary models incorporating geriatricians, randomized trials in frail populations, and real-world evidence on novel agents. This review advocates tailored strategies to optimize shared decision-making, enhance equity, and address current knowledge gaps through CGA-driven research, while proposing a pragmatic age- and frailty-stratified framework to support individualized cardiovascular assessment in elderly cancer patients. Full article

The past decade has witnessed significant expansion in both preclinical and approved receptor-targeted therapeutic cell modalities. These include immune cells engineered to express chimeric antigen receptors (CARs), and bispecific immune cell engagers developed for the treatment of cancer, autoimmune disorders, infectious diseases, and metabolic disorders. Although these approaches have produced remarkable clinical outcomes, cell therapy-associated off-target toxicities continue to present significant safety challenges. This review provides a framework for the rational design of optimized cell therapies aimed at enhancing therapeutic efficacy while minimizing adverse side effects. With the state-of-the-art advances in genomic profiling, artificial intelligence-driven design tools, and scalable manufacturing technologies, the outlook for next-generation receptor-targeted cell therapies is highly promising. Full article

Wound healing is a dynamic and highly coordinated process that involves inflammation, cell proliferation, angiogenesis, re-epithelialization, extracellular matrix remodeling, and tissue maturation. The altered expression of important signaling pathways, such as transforming growth factor-β (TGF-β)/Smad, nuclear factor-κB (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase (MAPK), and Wnt/β-catenin, may be responsible for slower wound healing, chronic inflammation, excessive fibrosis, and impaired tissue regeneration. Multifunctional nanomaterials are a promising strategy for tuning these highly coordinated processes due to their tunable physicochemical properties, high surface area, and the ability to deliver cargo, as well as the integration of antimicrobial, antioxidant, anti-inflammatory, and pro-angiogenic properties. The aim of current review is to summarize the potential of multifunctional nanomaterials to promote wound healing, with a focus on mechanisms of action and modulation of key cellular signaling pathways. A systematic review of the literature was conducted using PubMed, Scopus, Web of Science, and Google Scholar, searching for publications from 1996 to June 2026, and representative experimental, mechanistic, preclinical, and translational studies were critically evaluated. In this review, the authors discuss the role of nanomaterial properties, therapeutic payload, molecular targets, modulation of cellular signaling pathways, and regenerative effects. These platforms have been shown in in vitro and animal studies to influence inflammatory signaling, oxidative stress, angiogenesis, collagen remodeling, re-epithelialization, cellular proliferation, and migration. However, the modulation of these pathways are dose-responsive, time-dependent, and cell- and wound-stage-specific. Despite the promising therapeutic potential of nanomaterial-based wound care strategies, the available evidence remains predominantly preclinical, with relatively limited clinical data supporting their use in humans. Concerns regarding long-term toxicity, biodistribution, batch-to-batch reproducibility, sterilization, scalable manufacturing, regulatory approval, and commercial feasibility further challenge translation into clinical practice. Multifunctional nanomaterials may offer a promising approach for pathway-specific and multimodal wound management; however, comprehensive mechanistic studies, long-term safety and biodistribution assessments, and well-designed clinically relevant investigations are required to establish their efficacy, safety, and true translational potential. Full article

Engineered nanoparticles (ENPs) are being used with increasing frequency in industrial and consumer products across applications in industry, agriculture, ecology, and biomedicine. The unique physicochemical characteristics that make nanoparticles desirable in product design also affect their fate in the environment, interactions with living systems, and mechanisms of toxicity. Traditional testing methods and toxicological paradigms based on dissolved chemicals are poorly suited to understand ENP risks, primarily due to their small size, large SA:Vs, increased reactivity, and a surface chemistry that can be tuned during synthesis. Nanoparticle toxicity is dependent on complex relationships between particle characteristics, transformations in the environment, resulting exposure scenarios, and biological effects. Here we review ENP toxicity across a property → transformation → exposure → toxicity continuum, with a focus on how particle properties affect environmental and biological transformations relevant to toxicity. Properties such as size, shape, surface chemistry, dissolution, redox activity, and aggregation propensity are reviewed with respect to effects on transport and bioavailability, cellular uptake, biodistribution, and toxicity mechanisms. Transformations including aggregation, oxidation, dissolution/sulfidation, aging and eco-corona formation are discussed with regard to impacts on exposure and risk. Finally, major mechanisms of toxicity including oxidative stress, ion toxicity, membrane damage, inflammation, and genotoxicity are discussed with regard to nano–bio interactions. Analytical challenges associated with studying ENPs, shortcomings of the current risk assessment methods, and emerging Safe-by-Design approaches are also reviewed. Furthermore, connections between the fields of engineered nanoparticle toxicology and microplastics/nanoplastics are discussed, with particular focus on overlapping physicochemical properties, transformations, exposures, and biological mechanisms. Full article

Background and Clinical Significance: People with HIV (PWH) experience an elevated risk of atherosclerotic cardiovascular disease (ASCVD), driven by chronic immune activation, metabolic toxicities of antiretroviral therapy (ART), and traditional risk factors. Achieving target low-density lipoprotein cholesterol (LDL-C) levels is frequently impeded by adherence barriers, pharmacokinetic drug interactions, or muscle-related symptoms. Inclisiran is a hepatocyte-targeted small interfering RNA that halts proprotein convertase subtilisin/kexin type 9 synthesis, providing a long-acting therapeutic alternative. Case Presentation: We present two PWH with severe hypercholesterolemia and elevated cardiovascular risk on stable ART. Case 1 describes a 54-year-old male with a history of myocardial infarction presenting with persistent, refractory hypercholesterolemia on rosuvastatin and ezetimibe (baseline LDL-C 142 mg/dL). Case 2 describes a 58-year-old male with verified statin intolerance and inadequate response to ezetimibe (baseline LDL-C 194 mg/dL). Following subcutaneous inclisiran administration at Day 1 and Day 90, Case 1 achieved an 80.2% LDL-C reduction to 28 mg/dL at Month 6, and Case 2 achieved a 54.6% reduction to 88 mg/dL at Month 6 as monotherapy. Both patients tolerated therapy well, with stable CD4+ counts and sustained virological suppression. Conclusions: These cases illustrate that inclisiran can effectively lower LDL-C levels across primary and secondary prevention settings in PWH facing oral therapy limitations or statin intolerance. Provider-administered dosing every 6 months overcomes adherence challenges, supporting the inclusion of PWH in broader clinical pathways pending ongoing cardiovascular outcome trials. Full article

Gastric cancer is one of the malignancies with the highest incidence and mortality worldwide. Helicobacter pylori (H. pylori) infection is the primary driving factor in its development. The progression of gastric mucosal malignancy follows the Correa cascade model: “chronic non-atrophic gastritis → chronic atrophic gastritis (CAG) → intestinal metaplasia (IM) → dysplasia (Dys) → gastric cancer.” Currently, clinical management faces major challenges, including increasing antibiotic resistance in H. pylori, limited pharmacological options for gastric precancerous lesions, and treatment resistance and toxicity in established gastric cancer. This review synthesizes current evidence on BBR, COP, EPI, PAL, and JAT and organizes their reported actions into a three-tier intervention framework. At the first tier, etiologic and inflammatory interception, individual alkaloids suppress H. pylori persistence through direct antibacterial injury, urease inhibition, and modulation of bacterial virulence and antibiotic susceptibility, while attenuating infection-driven inflammatory and immune responses. At the second tier, modulation of precancerous mucosal progression, preclinical studies indicate that these compounds can ameliorate gastric glandular injury and may attenuate biological processes associated with progression toward intestinal metaplasia and dysplasia. At the third tier, antitumor and adjunctive intervention in established gastric cancer, alkaloids inhibit proliferation, induce cell-cycle arrest and apoptosis, suppress invasion and metastasis, and regulate non-coding RNA and epigenetic networks; BBR-centered preclinical studies further suggest potential chemosensitizing and supportive effects. This review integrates the five alkaloids BBR, COP, EPI, PAL, and JAT and systematically elucidates their mechanisms of action across the pathological continuum from H. pylori infection and chronic inflammation to precancerous lesions and ultimately gastric cancer. It establishes a stage-oriented, compound-specific analytical framework to clarify the pharmacological positioning of these compounds, identify priorities requiring further validation, and guide future mechanistic and translational research. Full article

The development of sustainable, biocompatible scaffolds with enhanced structural stability remains a primary challenge in bone tissue engineering. In this study, structurally reinforced nanocomposite scaffolds were successfully fabricated by integrating green-synthesized carbon quantum dots (CQDs) into a gelatin (G) matrix, offering an innovative platform that mimics the organic–inorganic interfaces of natural bone tissue. The CQDs were derived from oatmeal via a sustainable, green hydrothermal route, serving simultaneously as zero-dimensional reinforcing fillers and bioactive agents within the biopolymer network. To ensure an additive-free fabrication process that avoids toxic chemical cross-linkers, dehydrothermal (DHT) treatment was employed, successfully modulating the interfacial and chemical cross-linking interactions between the gelatin chains and the oxygen-rich surface groups of the CQDs. Structural characterization confirmed the uniform dispersion of CQDs (average diameter 7–8 nm) within the porous gelatin framework. The incorporation of CQDs significantly improved the physicochemical properties of the scaffolds; the G/CQD 5% formulation emerged as the optimal composition, exhibiting a 118% increase in compression modulus compared to pristine gelatin. The composite demonstrated tuned swelling kinetics and a significantly reduced degradation rate, restricting mass loss after 14 days of incubation to approximately 24% compared to 40% for pristine gelatin, which is essential for maintaining a structural template during the initial stages of tissue formation. Bioactivity assays in simulated body fluid (SBF) confirmed the rapid, biomimetic induction of a crystalline hydroxyapatite layer with a natural Ca/P ratio of 1.61 within 14 days. Furthermore, preliminary in vitro assessments using Human Skin Fibroblasts (HSFs) confirmed excellent general cytocompatibility, with cell viability exceeding 90%. This study highlights the unique potential of utilizing biomass-derived carbon nanostructures and clean manufacturing processing to engineer multifunctional scaffolds with enhanced structural stability and intrinsic bioactivity for potential bone defect repairs. Full article

Acute and chronic inflammation underlies the pathogenesis of numerous diseases, including autoimmune disorders, atherosclerosis, infections, and cancer. Although non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are widely used to control inflammation, their clinical utility is limited by adverse effects such as gastrointestinal toxicity and immunosuppression. Specialized pro-resolving mediators (SPMs), a family of endogenous lipid mediators derived from omega-3 fatty acids, have emerged as promising therapeutics because they actively promote the resolution of inflammation without suppressing host immunity. However, their clinical translation is hindered by poor chemical stability, rapid metabolic degradation, and short circulation half-lives. To overcome these limitations, a variety of delivery platforms—including liposomes, extracellular vesicles, PLGA nanoparticles, and hydrogels—have been developed to improve SPM stability, pharmacokinetics, and therapeutic efficacy. This review summarizes the cellular targets of SPMs, current delivery challenges, and emerging strategies for cell- and tissue-specific SPM delivery. We also discuss future opportunities for targeted SPM therapies in the treatment of inflammatory diseases and cancer. Full article

Marked interindividual variability in drug response remains a major challenge in clinical pharmacology and cannot be fully explained by host genetics alone. Increasing evidence indicates that the gut microbiota constitutes an additional determinant of drug efficacy and toxicity through bidirectional interactions with pharmacological therapies. This recognition has led to the emergence of pharmacomicrobiomics, a field that investigates how microbial communities influence drug disposition and response, and how drugs, in turn, alter the microbiome. Microbiome-mediated effects on drug efficacy and toxicity have been described across several therapeutic areas, including oncology, multiple sclerosis, and type 2 diabetes mellitus. Although these findings are promising, most mechanistic evidence derives from preclinical and animal studies, with relatively limited validation in controlled clinical trials. Strategies to modulate the gut microbiota, including prebiotics, probiotics, and faecal microbiota transplantation, have shown preliminary promise in optimising drug efficacy and reducing adverse effects, although methodological heterogeneity and incomplete mechanistic understanding limit their current clinical application. The identification of robust microbiome-derived biomarkers and the integration of multi-omics approaches, particularly metabolomics, are expected to accelerate the translation of pharmacomicrobiomics into precision medicine. This review summarises current evidence regarding microbiome–drug interactions, the mechanisms underlying microbiome-mediated modulation of pharmacokinetics and pharmacodynamics, emerging therapeutic strategies, and the challenges that remain before pharmacomicrobiomics can be implemented in clinical practice. Full article

Background/Objectives: Chimeric antigen receptor (CAR)-T cell therapy has achieved substantial clinical success in haematological malignancies but has shown limited efficacy against solid tumours. Key barriers include inadequate tumour trafficking, immunosuppressive tumour microenvironments, poor selectivity and heterogeneity of antigen expression, and challenges related to safety and manufacturing. Biomaterial-based technologies have emerged as a potential strategy to address many of these limitations. This review aims to critically evaluate biomaterial approaches designed to enhance CAR-T cell therapy of solid tumours and assess their translational potential. Methods: A narrative review of recent pre-clinical translational studies was conducted, focussing on biomaterial platforms developed to improve CAR-T cell delivery, persistence, functionality, safety control, and manufacturing efficiency in solid-tumour settings. Approaches were analysed according to their mechanisms of action, therapeutic benefits, and stage of translational readiness. Results: Biomaterial strategies, including nanoparticles, injectable and implantable hydrogels, scaffolds, and hybrid delivery systems, have improved CAR-T infiltration, survival, and therapeutic efficacy in several solid-tumour models. Localised delivery of cytokines and other immunomodulatory cues enabled improved spatio-temporal control of CAR-T activation, reducing systemic toxicity, and increasing persistence. Additional applications include amplified ex vivo CAR-T expansion and support for non-viral or in vivo CAR-T generation. However, increased material complexity was frequently associated with challenges in scalability, regulatory approval, and long-term safety. Conclusions: Biomaterial-enabled approaches offer a versatile toolkit to address key biological and translational barriers limiting CAR-T cell therapy of solid tumours. Strategies based on clinically familiar materials and simplified designs appear most suitable for near-term clinical translation, emphasising the need to balance engineering innovation with safety, scalability, and integration into existing clinical workflows. Full article