Search Results (2,217)

In response to the plastic pollution crisis, bioplastics emerged as a sustainable alternative. However, low degradation rate and abiotic decomposition generate micro- and nanoplastics. These particles enter the food chain, establishing oral intake as a key route of human exposure. This review gathered studies on the biotransformation of bioplastics in the gastrointestinal tract and on their toxicity in human cells and murine models. Most studies focused on polylactic acid particles due to widespread use in food packaging. Under simulated gastrointestinal conditions in vitro, particles were modulated, resulting in cavity and pore formation, fragmentation, lipase competition, protein corona formation, and alterations in the gut microbiota (including Selenomonadaceae, Bifidobacterium, and Prevotellaceae). Also, particle breakdown increases surface area, enhancing interactions with biomeiolecules and causing higher in vitro and in vivo toxicity. Indeed, pro-inflammatory cytokine secretion, oxidative stress induction, and redox imbalance were found in both models. In mice, alterations in gut microbiota involving Bacillales indirectly mediated hepatotoxicity, leading to uric acid and triglyceride accumulation. Furthermore, microbiota adaptation over time was suggested with an increase in microorganisms and the potential conversion of L-lactic into harmful D-lactic acid. Despite limited studies, this review highlighted that ingested bioplastic-derived micro- and nanoplastics can lead to toxic effects. Full article

Ferroptosis is an iron-dependent form of regulated cell death characterized by lipid peroxidation and failure of cellular antioxidant defenses. Increasing evidence indicates that ferroptosis contributes to the biological effects of radiotherapy and influences both tumor radiosensitivity and normal tissue injury. Because radiotherapy is a central treatment modality for many head and neck cancers, understanding how ferroptosis interacts with radiation responses has important translational implications. Ionizing radiation can induce ferroptosis through reactive oxygen species generation, disruption of glutathione metabolism, suppression of the SLC7A11–GSH–GPX4 antioxidant axis, and remodeling of membrane lipid composition. Conversely, tumor cells frequently develop radioresistance by reinforcing ferroptosis-suppressive pathways, including enhanced cystine transport, lipid desaturation, and metabolic adaptation. In head and neck cancers such as head and neck squamous cell carcinoma, nasopharyngeal carcinoma, oral squamous cell carcinoma, and thyroid malignancies, experimental studies show that modulation of ferroptosis significantly alters radiation response. Strategies that promote ferroptosis—including inhibition of antioxidant defenses, targeting of lipid metabolism, and modulation of iron homeostasis—have demonstrated radiosensitizing effects in preclinical models. However, ferroptosis may also contribute to radiation-induced normal tissue injury, particularly in oxidative stress-sensitive organs such as the salivary glands. This review summarizes the molecular basis of ferroptosis in radiotherapy, examines its role in radiosensitivity and radioresistance in head and neck cancers, and discusses therapeutic strategies to exploit ferroptosis while minimizing normal tissue toxicity. Full article

Background/Objectives: The purpose of this study was the chemical design, synthesis, and evaluation of the antimicrobial and antibiofilm potentials of 20 novel thiazolyl-methylthio-thiadiazole hybrid compounds (6a–j and 8a–j). Methods: The compounds were designed as structural analogues of halicin with two points of variation and were synthesized through a process with multiple condensation steps. The compounds were evaluated in vitro through MIC determinations for the antimicrobial activity and percentage of biofilm inhibition, and in silico, respectively, through molecular docking, druggability, and ADMETox prediction. A 2D-QSAR study was conducted for antimicrobial activity using the Free-Wilson model. Results: In terms of antibacterial activity, all compounds displayed important activity on the tested strains (MICs = 15.62–250 μg/mL), except against Staphylococcus aureus. Regarding the antifungal activity, the effect against Candida albicans was similar to fluconazole in most cases (MIC = 15.62 μg/mL). With respect to the antibiofilm activity, the most effective activity was registered against the Pseudomonas aeruginosa biofilm. The in vitro results for the antibacterial activity against Escherichia coli were correlated with the observations drawn in the molecular docking study on the ATPase domain of the GyrB subunit of E. coli. The in silico predictions of the molecular properties concluded that all compounds have good druggability properties, while the ADMETox predictions concluded that the compounds could have low gastrointestinal absorption and blood–brain barrier permeation capacity, but raised safety flags (e.g., hepatotoxicity and high acute oral toxicity). The 2D-QSAR study concluded that the thiazolyl-methylthio-thiadiazole scaffold had the highest contribution to antimicrobial activity in almost all cases. Conclusions: The two series of compounds highlight the impact of structural modulations of the scaffold and its substituents on the investigated biological activities. Full article

Background/Objectives: The oral administration of donepezil has been shown to have common side effects due to systemic drug delivery, with fluctuations in blood and brain donepezil concentrations. Therefore, we obtained nanostructured lipid carriers loaded with donepezil (donepezil–NLC) for nose-to-brain targeting. Methods: The obtained NLCs were characterized by measurements of particle size, the polydispersity index, zeta potential, encapsulation efficiency, atomic force microscopy, Differential Scanning Calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, and in vitro release studies. Plasma and brain pharmacokinetic studies in Wistar rats were carried out to determine brain targeting. Results: Donepezil–NLC showed low polydispersity and nanometric size, high zeta potential, and high drug entrapment efficiency. Microscopy images showed spherical particles with regular surfaces. Thermal analysis, X-ray diffraction, and FTIR-ATR suggested the formation of an amorphous lipid matrix and the incorporation of donepezil molecularly dispersed within the lipid matrix. In vitro drug release studies demonstrated a biphasic drug release pattern with an initial burst followed by sustained release, with results better fitted to the Korsmeyer–Peppas model (n-value > 0.5). Following the nasal administration of donepezil–NLC, brain pharmacokinetic studies in Wistar rats demonstrated a significant improvement in bioavailability. Compared to the intravenous injection of donepezil, the AUC^0–ꝏ value was 10.5-fold higher. Drug targeting efficiency and direct transport percentage showed extremely higher values, suggesting nose-to-brain targeting after donepezil–NLC intranasal administration. Conclusions: Donepezil–NLC has proven to be an efficient drug delivery system for the nose to the brain, which may reduce systemic toxicity and improve Alzheimer’s therapy with low doses of donepezil and fewer adverse effects. Full article

Background/Objectives: Financial toxicity (FT) is increasingly recognised as a critical dimension of the cancer care continuum, reflecting both objective financial burden and subjective financial distress arising from cancer-related care. Head and neck cancers (HNC) may be particularly vulnerable to FT because treatment often involves multimodal care, functional morbidity, prolonged rehabilitation, and disruption to employment. This scoping review mapped and synthesised the literature on FT in a focused subset of head and neck cancers (HNC), namely malignancies of the oral cavity, oropharynx, nasopharynx, sinonasal tract, and major and minor salivary glands. Methods: A scoping review was conducted in accordance with the methodological guidance of the Joanna Briggs Institute for scoping reviews to identify and synthesise studies addressing FT in the selected HNC subsites. Searches were undertaken in MEDLINE, Embase, Scopus, Web of Science, CINAHL, EconLit, and Global Index Medicus for English-language studies published between 1 January 2015 and 1 January 2025. The search window was restricted to this period to capture the more contemporary evolution of FT as a distinct research construct in oncology. Eligible studies included adult patients and reported patient-level FT outcomes, including direct costs, indirect costs, out-of-pocket expenditure, financial hardship, financial distress, employment disruption, or related economic strain. Findings were synthesised narratively and organised thematically. Results: Twenty-five studies published between 2015 and 2025 were included. The evidence base was dominated by cross-sectional and retrospective designs, with limited prospective follow-up and very little intervention-focused research. FT was conceptualised heterogeneously across studies, spanning direct expenditure, indirect and non-medical costs, subjective financial distress, and coping-related consequences. Questionnaire-based approaches were used in 13 studies, but only a smaller subset employed FT-specific instruments such as COST. Across the literature, FT was most commonly associated with lower income, weaker financial protection, employment disruption, rural residence in some settings, and more intensive treatment. Reported downstream associations included poorer quality of life, psychological distress, care alteration, and work-related burden, although evidence for treatment delay or survival effects was more limited and should be interpreted cautiously. Conclusions: In this focused HNC subset, FT appears multidimensional, socially patterned, and clinically relevant. However, the literature remains methodologically fragmented, with inconsistent measurement and sparse longitudinal evidence. Future work should prioritise validated and tumour-specific assessment strategies, prospective study designs, and evaluation of mitigation interventions that address both direct and indirect burden across the cancer continuum. Full article

Background/Objectives: Oral cancer remains a major global health challenge, with persistent limitations in treatment efficacy and significant therapy-related morbidity. Probiotics, owing to their immunomodulatory, anti-inflammatory, and microbiota-regulating properties, have emerged as potential therapeutic and adjuvant agents. This scoping review aimed to systematically map and critically appraise preclinical and clinical evidence regarding the therapeutic and supportive effects of probiotics in oral cancer. Methods: A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar without temporal restrictions, including studies published up to February 2026. Eligible studies comprised in vitro, in vivo, and clinical investigations evaluating the effects of live or non-viable probiotic interventions on oral cancer biology and related clinical outcomes. Results: Twenty-one studies were included: 13 in vitro, 3 in vivo, and 6 clinical studies. Preclinical evidence indicates that strains such as Lactiplantibacillus plantarum, Lactobacillus acidophilus, and Lacticaseibacillus paracasei exert selective antiproliferative effects (up to 85% inhibition) via apoptosis induction, modulation of PTEN/MAPK and NF-κB signaling, and reduction in pro-inflammatory mediators. In vivo models demonstrated tumor growth suppression and improved survival without significant toxicity. Clinically, probiotics reduced treatment-induced oral mucositis, improved salivary function, and enhanced microbiota stability and patient-reported outcomes. However, evidence on direct oncological endpoints remains limited. Conclusions: Probiotics demonstrate biologically plausible, strain-specific antitumor and supportive effects, with the strongest evidence supporting their role as adjunctive agents, particularly in managing treatment-related complications. Further well-designed in vivo and clinical studies are required to define optimal strains, dosing strategies, and integration with standard oncologic treatments. Full article

Since their initial discovery in 2003, carbon quantum dots (CDs) have attracted significant attention due to their unique optical properties and potential biomedical applications. This review critically examines the past 20 years of research on CDs, with a particular focus on cytotoxicity studies from the last decade. CDs, typically less than 10 nm in size, have been synthesized from various organic and inorganic precursors using multiple methods, including hydrothermal, microwave, and chemical reduction techniques. Their properties can be finely tuned by modifying synthesis parameters and incorporating dopants. The preliminary studies on the biological effects of CDs were published in 2013, highlighting their antibacterial properties and low toxicity in certain contexts. Subsequent research has explored their bioactivity, including their application in drug delivery, bioimaging, and photothermal therapy. However, the cytotoxicity of CDs remains a critical area of investigation. Further studies have demonstrated that surface functional groups, charge, concentration, and size significantly influence their interaction with biological systems. For instance, CDs with positive surface charges exhibit higher cellular uptake and greater cytotoxicity compared to their negatively charged counterparts. In vivo studies utilizing animal models such as zebrafish, mice, and planarians have provided valuable insights into the potential toxicological impacts of CDs. The results indicate that while CDs generally exhibit low toxicity at certain concentrations, high doses can lead to adverse effects, including oxidative stress, organ damage, and disrupted cellular functions. Notably, the route of administration (oral, intravenous, or intraperitoneal) also affects the observed toxicity profiles. The goal of this review is to integrate the results of various studies to provide a balanced perspective on the potential risks and benefits of CDs, guiding future research and applications in nanomedicine. This review underscores the necessity for standardized and comprehensive toxicological evaluations of CDs to fully understand their safety and efficacy for biomedical applications. Full article

Annona cherimola is a plant species widely used in Mexican traditional medicine, particularly in the management of diabetes. This study aimed to investigate the antihyperglycemic properties of the petroleum ether extract of A. cherimola leaves (PEEAcL), as well as to evaluate their effects on glycated hemoglobin and toxicity. In addition, the work was directed to determine its potential as an SGLT-1 and α-glucosidase inhibitor. The effect as a potential SGLT-1 and α-glucosidase inhibitor of PEEAcL was evaluated utilizing intestinal glucose absorption (IGA), oral glucose tolerance (OGT), oral sucrose tolerance (OST) and intestinal sucrose hydrolysis (ISH) tests. PEEAcL administered at doses of 200 mg/kg showed significant antihyperglycemic activity after 1 h of treatment, and the maximum effect was seen at 4 h in male and female diabetic mice. In the OST, OLT, and OGT tests, PEEAcL generated a reduction in the postprandial glucose peak at 2 h after the administration of a carbohydrate load, showing an effect comparable to that of acarbose and canagliflozin. In the IGA trial, PEEAcL significantly reduced glucose uptake in the small intestine. Similarly, in the ISH, PEEAcL recorded a significant reduction in glucose concentration in the external aqueous medium. Taken together, these results suggest that the antihyperglycemic effect of PEEAcL could be mediated, at least in part, by inhibition of SGLT-1 and the enzyme α-glucosidase. Full article

Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon characterized by dysregulated mucosal immunity and progressive epithelial injury. Upadacitinib (UPA), a selective Janus kinase 1 (JAK1) inhibitor, has demonstrated clinical efficacy in UC, but its therapeutic application is often constrained by adverse effects arising from systemic drug exposure. This underscores the need for advanced, site-specific delivery systems that enhance local efficacy while minimizing systemic toxicity. Here, we developed a colon-targeted natural lipid nanoparticle formulation of UPA (UPA-nLNP) to improve therapeutic performance and safety. UPA-nLNP was prepared by thin-film hydration using digalactosyldiacylglycerol (DGDG), monogalactosyldiacylglycerol (MGDG), and phosphatidic acid (PA), mimicking the lipid composition of ginger-derived exosomal particles, and was characterized for particle size, surface charge, and encapsulation efficiency. The formulation exhibited excellent mucus-penetrating capability and was evaluated in a dextran sulfate sodium (DSS)-induced acute colitis model in C57BL/6 mice following oral administration (5 mg/kg). Pharmacokinetic analysis demonstrated increased colonic accumulation with reduced systemic exposure compared to free UPA. Treatment with UPA-nLNP improved body weight recovery, reduced disease biomarkers, and suppressed key proinflammatory cytokines in the colon, with no evidence of systemic toxicity. This innovative strategy holds strong potential to enhance the clinical utility of JAK1 inhibitors by providing a safer and more effective therapeutic approach for ulcerative colitis. Full article

IgA nephropathy is the most common primary glomerulonephritis worldwide and a leading cause of chronic kidney disease and kidney failure, with geographic and ancestral variation and a course ranging from asymptomatic urinary abnormalities to progressive loss of kidney function. This narrative review links the multi-hit model to risk stratification, biomarkers, current management, and emerging therapies, and highlights implementation gaps. Risk assessment is longitudinal, prioritizing proteinuria and estimated glomerular filtration rate trajectories and integrating Oxford MEST-C, prediction tools, and biomarker and multi-omics approaches, while recognizing limitations in histologic reproducibility and model calibration. Current management is anchored in optimized supportive care aimed at sustained proteinuria reduction and kidney protection, including intensive blood pressure control with maximal tolerated renin–angiotensin system blockade, dietary sodium restriction and lifestyle measures, and sodium–glucose co-transporter 2 inhibitors for eligible patients. For selected higher-risk patients with persistent proteinuria despite optimized supportive care, immunomodulatory strategies are discussed, including systemic corticosteroids and targeted-release budesonide (Nefecon), emphasizing structured toxicity risk mitigation and cautioning against assuming interchangeability among alternative oral budesonide formulations. Emerging therapies are organized around mechanism-aligned targets across the BAFF/APRIL axis, complement pathways, and endothelin-based approaches, with growing interest in sequencing and combination regimens layered on supportive care. Key gaps include reliance on surrogate endpoints, limited long-term durability and safety data, and uneven evidence for special populations. Full article

(1) Background: Hypofractionated radiotherapy and immunotherapy (IT) are possible treatment options for HNSCC patients unsuitable for standard curative treatment, yet no high-level evidence supports their combined use. We aim to report on the clinical outcome of a single-center cohort of HNSCC patients treated with a hypofractionated radiotherapy (hypoRT) regimen in combination with IT alone or chemo-immunotherapy (CT-IT). (2) Methods: We enrolled a cohort of elderly and frail HNSCC patients unsuitable for standard curative treatment, deemed candidates to undergo hypoRT in a sequential strategy (time interval < 6 months), followed or preceded by IT alone (hypoRT_IT) or CT-IT. We selected our sample using the Geriatric 8 (G8) score and the Charlson Comorbidity Index (CCI). (3) Results: At a median follow-up of 11 months (IQR 5–20), the median locoregional control (LRC) was 12 months (95% CI 7.0–17.1) with a 1-year progression-free survival rate of 63%. For the hypoRT-IT group, the median overall survival was 12 months (95% CI 0–24). No grade (G) 4–5 in-field acute side effects were observed, while one case of G3 oral mucositis and two cases of G3 radiation dermatitis were reported. (4) Conclusions: A sequential combination of checkpoint inhibitors and hypoRT may provide clinical benefit with acceptable toxicity in frail and elderly patients with advanced HNSCC unfit for standard therapy. Full article

Background and Objectives: Tamoxifen, a cornerstone selective estrogen receptor modulator in breast cancer therapy, is increasingly recognized to be associated with retinal toxicity characterized by mitochondrial dysfunction, oxidative stress, lipid peroxidation, and oxidative DNA injury. By targeting mitochondrial bioenergetic dysfunction and redox disequilibrium, adenosine triphosphate (ATP) emerges as a biologically plausible candidate for retinal cytoprotection. This study aimed to evaluate the protective effect of ATP against tamoxifen-induced retinal toxicity in a rat model. Materials and Methods: Twenty-four male albino Wistar rats were randomly assigned to four groups: healthy control (HG), ATP-alone (ATPG, 4 mg/kg, intraperitoneally), tamoxifen-alone (TAMG, 5 mg/kg, orally), and tamoxifen plus ATP-treated (ATAG; ATP, 4 mg/kg, intraperitoneally; tamoxifen, 5 mg/kg, orally). Treatments were administered once daily for 30 days. Oxidative stress markers (malondialdehyde, total glutathione), antioxidant enzyme activities (superoxide dismutase, catalase), and oxidative DNA damage (8-hydroxy-2′-deoxyguanosine) were assessed in ocular tissues. Retinal histopathological evaluation included hematoxylin–eosin staining with semiquantitative assessment of edema, vascular congestion, polymorphonuclear leukocyte infiltration, and cytoplasmic vacuolization, together with quantitative measurements of retinal layer thicknesses and ganglion cell layer (GCL) cell counts. Results: Tamoxifen administration induced marked oxidative stress, antioxidant depletion, and increased oxidative DNA damage in ocular tissues, accompanied by significant thickening of retinal layers, reduced GCL cell counts, and pronounced disruption of retinal architecture. By comparison, ATP co-administration significantly suppressed lipid peroxidation and restored antioxidant defenses, thereby reducing oxidative DNA damage and preserving retinal structural integrity, as reflected by partial normalization of retinal layer thicknesses, preservation of GCL cell counts, and the presence of only mild residual edema. Conclusions: These findings indicate that ATP attenuates tamoxifen-induced retinal toxicity by supporting mitochondrial energy balance and redox homeostasis. Accordingly, ATP administration may represent a promising protective approach for reducing retinal injury associated with long-term tamoxifen therapy. Full article

Oral infections caused by antibiotic-resistant bacteria represent an emerging biomedical hazard and growing challenge for modern dentistry. To address this issue, Ag– and Cu–ZnO nanocomposites (NCs) were synthesized using ZnO carrier to combat the oral pathogens Streptococcus mutans and Streptococcus sobrinus. A comprehensive analysis of chemically synthesized metal oxide nanocomposites (MONCs) was performed, combining physicochemical characterization (TEM, XRD, ζ-potential, DLS, pH, and PFO/PSO kinetic models) with biological toxicity assessment (MIC, ATR–FTIR, SEM, and FAMEs) to better understand their antimicrobial mechanisms. The results confirmed that the synthesized nanoproducts fulfill the criteria for nanomaterials (NMs) (particle size < 100 nm). Among them, Ag–ZnO exhibited the highest antibacterial activity against both strains (MIC = 50 mg L⁻¹). Kinetic modeling revealed faster and more efficient Ag ion release from Ag–ZnO NCs compared to Cu from Cu–ZnO NCs. Molecular analyses indicated strong MONC–bacterial interactions at the cell surface, leading to changes in protein secondary structures, alterations in lipid composition, and disruption of Gram-positive bacterial membranes. Additionally, Ag–ZnO inhibited chain and cluster formation in both bacterial species, while Cu–ZnO affected only S. sobrinus. Overall, Ag– and Cu–ZnO NCs show strong potential as antimicrobial agents against oral pathogens. Full article

Background: Bee-derived products are rich in bioactive compounds with antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties. Interest is growing in their potential role as adjuncts in supportive nutritional oncology, particularly for preventing and managing treatment-related toxicity symptoms in patients receiving chemotherapy and/or radiotherapy. Methods: A systematic search of human and preclinical studies was conducted in PubMed/MEDLINE, Web of Science, and Scopus from January 2000 to December 2025. Search terms combined bee-related product keywords with oncology-related keywords. Eligible studies included in vitro and in vivo preclinical models as well as clinical studies assessing biological properties, clinical outcomes, safety, and issues of product standardization. Results: Preclinical and clinical studies indicate that beehive products reduce oxidative stress, modulate inflammatory signaling pathways, exhibit antimicrobial activity against wound pathogens, and promote tissue repair. Results are most consistent for oral mucositis and for symptom management in head and neck cancer, where some studies report reduced pain, improved mucosal healing, and better nutritional status. Conclusions: This literature review identifies honey and beehive products as promising functional foods for improving oncological patient care. Further large studies are needed, as the evidence is heterogeneous across sample size, product composition, outcome measures, and therapeutic preparations. Full article

Background: Hormone receptor-positive (HR+), Human Epidermal growth factor Receptor 2 (HER2-negative) metastatic breast cancer (MBC) represents a substantial proportion of breast cancer cases in Saudi Arabia. Despite the established efficacy of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, particularly Palbociclib, in randomized control trials, real-world data from local institutions in Saudi Arabia remain limited. Objectives: This study aimed to evaluate progression-free survival (PFS), overall survival (OS), and toxicity profile among HR+, HER2-negative MBC female patients treated with Palbociclib at King Fahad Medical City (KFMC). Methods: A retrospective study was conducted on female patients with HR+/HER2-negative MBC treated with oral palbociclib combined with endocrine therapy (ET) at KFMC between January 2021 and September 2024. Data were collected from electronic health records. Descriptive statistics were conducted using mean for continuous variables and frequency for categorical variables. Survival analyses were conducted using Cox regression, log-rank tests and Kaplan–Meier analysis. Results: A total of 169 female patients with HR+/HER2− MBC were included. In the first-line setting, the median PFS was 20.14 months (95% CI: 14.65–30.49), compared with 11.3 months (95% CI: 7.98–not estimable) in the second-line setting. For OS, the median OS values were 53.1 months (95% CI: 41.2–not estimable) in the first-line group and 23.7 months (95% CI: 18.5–not estimable) in the second-line group. Significant predictors of shorter PFS included age, Body Mass Index (BMI), type of ET, cancer type, line of therapy, family history of cancer, and history of VTE. Visceral metastasis (HR = 3.087; p = 0.0229) and ECOG performance status of 4 (HR = 13.86; p = 0.0156) were associated with significantly shorter OS. The most common hematological adverse events (AEs) were neutropenia (45.6%), followed by anemia (5.9%), leukopenia (5.3%), and back pain (5.3%). Most toxicities were managed with dose reduction, holding treatment, or supportive care. Conclusions: Palbociclib demonstrated favorable survival outcomes and a manageable safety profile, with neutropenia being the most common AE. This study provides region-specific real-world evidence supporting the use of Palbociclib in HR+/HER2− MBC. These findings align with global trial data and highlight the importance of individualized treatment in clinical practice. Full article