Search Results (4,447)

Background/Objectives: Allomyrinasin is a cationic antimicrobial peptide derived from Allomyrina dichotoma larvae with known antibacterial and anti-inflammatory properties; however, its effects on migration-related mechanisms in oral squamous cell carcinoma (OSCC) remain poorly understood. This study investigated the anti-migratory potential of allomyrinasin in OSCC cells, focusing on Na⁺/HCO₃⁻ cotransporter (NBC) activity as a key migratory module. Methods: NBC activity was assessed in YD-38 OSCC cells treated with allomyrinasin. Cell migration was evaluated by wound healing and Transwell assays, and MMP expression. Intracellular reactive oxygen species (ROS), apoptosis-related markers, and lamin A/C expression were analyzed using fluorescence-based assays and gene expression analysis. Results: Allomyrinasin inhibited NBC activity and suppressed cell migration without substantial loss of cell viability. MMP-13 was selectively downregulated among the tested MMPs. Lamin A/C expression was markedly upregulated, suggesting enhanced nuclear stiffness that may restrict confined cell migration. Intracellular ROS levels were elevated, and apoptotic progression was confirmed by increased Annexin V/PI positivity along with downregulation of B-cell lymphoma 2 (BCL2) and upregulation of BCL-2–associated X genes (BAX), through a p53-independent pathway consistent with the TP53-deleted status of YD-38 cells. Conclusions: Allomyrinasin suppresses OSCC cell migration by targeting NBC activity as a key component of the migratory machinery, accompanied by oxidative stress induction and pro-apoptotic signaling. These findings identify allomyrinasin as a potential anti-migratory therapeutic candidate and highlight NBC activity as a promising target for attenuating cancer metastasis. Full article

Background: Abemaciclib (ABM) in combination with tamoxifen (TAM) is an extremely significant treatment regimen for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. It is approved for patients to reduce the risk of cancer recurrence. A bioanalytical method for the simultaneous determination of this new anti-breast cancer combination and its pharmacokinetic application has not yet been reported. Methods: An ultra-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method was developed for quantifying ABM, TAM, and its metabolites, including abemaciclib active metabolites M2, M18, and M20 and tamoxifen active metabolite N-desmethyl tamoxifen (NDTAM), in rat plasma using econazole as the internal standard (IS). Chromatographic separation was achieved on a Kinetex C18 column (100 × 2.1 mm ID, 2.6 µm) using gradient elution with 5 mM ammonium formate in water (eluent A) and 5 mM ammonium formate in water/methanol (1:9, v/v, eluent B) at a flow rate of 0.4 mL/min. Detection was performed on a TSQ Fortis Plus mass spectrometer employing multiple reaction monitoring mode under positive electrospray ionization. Results: The developed method was validated according to the guidance of the FDA. Linearity in rat plasma (ng/mL) was achieved from 1 to 1000 for ABM, TAM, and M20; 3 to 1000 for M2; 5 to 500 for M18; and 1 to 500 for NDTAM; with correlation coefficients ranging from 0.9991 to 0.9931 for all analytes using a weighting factor of 1/X². The lower limit of detection (LLOD) ranged between 0.3 and 1.5 ng/mL for all drugs. The accuracy ranged from 96 to 108% and the precision was less than 7.6% RSD for all analytes. For the first time, the newly developed approach was effectively used in a pharmacokinetic study on the simultaneous oral administration of ABM and TAM in rats that received 30.0 mg/kg of ABM and 8.0 mg/kg of TAM. Conclusions: To the best of our knowledge, this is the first reported UPLC–MS/MS method for the assay of ABM, TAM, and its active metabolites in plasma. This method offers a bioanalytical tool for assessing the pharmacokinetics of ABM and TAM. Therefore, this study makes a definite significant contribution to the field of bioanalytical research. Further validation in human plasma is required for future clinical or therapeutic drug monitoring applications, as the approach was developed in an animal model. Full article

Background/Objectives: Oral mucositis (OM) is a common complication in laryngeal cancer (LC), during radiotherapy (RT), significantly affecting patient outcomes. Identifying sensitive biomarkers to predict OM severity is therefore crucial. MicroRNAs, which regulate inflammatory pathways involved in OM, are promising candidates. This retrospective study aimed to evaluate plasma miRNA-548L as a predictive biomarker for the occurrence and severity of OM in LC patients undergoing RT. Methods: The expression levels of the selected miRNAs were analyzed in plasma samples obtained from 76 LC patients prior to the initiation of RT. Bioinformatics analyses were performed to identify molecular pathways regulated by miRNA-548L and their potential link to the pathogenesis of OM. Results: Significantly decreased levels of the studied miRNA were observed in the plasma of LC patients who developed severe OM after the IV^th (p < 0.001), V^th (p = 0.039), VI^th (p < 0.001), and VII^th (p < 0.001) cycles of RT. Additionally, the expression of miRNA-548L enabled reliable differentiation between patients who developed severe OM during the IV^th (AUC = 0.81, p < 0.001), V^th (AUC = 0.77, p < 0.001), VI^th (AUC = 0.82, p < 0.001), and VII^th (AUC = 0.86, p < 0.001) weeks of treatment. Importantly, lower expression of miRNA-548L (HR = 3.12; p = 0.010) was significantly associated with shorter median overall survival (OS). Conclusions: Pretreatment plasma miRNA-548L shows potential as a biomarker for predicting severe OM in LC patients undergoing RT. Notably, reduced miRNA-548L expression is associated with shorter OS and may help stratify patients by OM severity. Full article

Background/Objectives: The neutrophil-to-lymphocyte ratio (NLR) is a simple biomarker reflecting systemic inflammatory status and has been investigated in head and neck cancer (HNC) as a potential prognostic indicator. Its role in relation to radiotherapy-related toxicity remains uncertain. The aim of this study was to provide a descriptive evaluation of NLR values in relation to oral mucositis severity and swallowing-related quality of life in patients undergoing radiotherapy-based treatment. Methods: We retrospectively evaluated 32 patients with locally advanced HNC treated with radiotherapy, with or without concomitant chemotherapy, in the definitive or adjuvant setting (March 2025–January 2026). NLR was calculated at baseline (T0), at a predefined mid-treatment timepoint (T3), and during week 6 of treatment (T6). Mucositis severity was assessed using CTCAE and the Oral Mucositis Assessment Scale (OMAS), while swallowing-related quality of life was measured using the MD Anderson Dysphagia Inventory (MDADI). Relationships between NLR values and toxicity endpoints were descriptively assessed using Spearman correlation analysis. Results: No statistically significant correlations were observed between NLR values and OM severity or swallowing-related outcomes at any evaluated timepoint. At T3, non-significant correlations were observed between NLR and CTCAE mucositis grade and between NLR and MDADI global score. No statistically significant correlations were observed between NLR values and OMAS at any evaluated timepoint. Conclusions: In this retrospective cohort, no association between NLR and radiotherapy-related mucositis severity or swallowing-related quality of life was demonstrated. These findings are descriptive and limited by the small sample size, the retrospective design, and the absence of control for potential confounding factors. No inferential or causal conclusions can be drawn. Further prospective studies with larger and more homogeneous cohorts are required to better characterize NLR behavior in this clinical setting. Full article

Metabolic changes in saliva are known to be closely associated with the presence of non-oral cancers, particularly breast cancer. The diagnostic and prognostic potential of salivary biomarkers in breast cancer has been demonstrated, but their applicability for assessing therapy response has not yet been established. The aim of this study was to comprehensively analyze clinical, pathological, molecular, and salivary characteristics when assessing the response to neoadjuvant chemotherapy for breast cancer. The study included 361 breast cancer patients undergoing their first course of chemotherapy and 127 healthy volunteers without breast pathologies. Saliva samples were collected from all volunteers before treatment. Saliva analysis results for amino acids, lipids, and tumor markers were compared with tumor pathomorphism assessment after breast cancer surgery. The proportion of patients with a complete response to therapy was statistically significantly lower after menopause, and in those with HER2-negative breast cancer, moderate tumor differentiation, and high estrogen and progesterone receptor expression. For the first time, a body mass index (BMI) greater than 25 and low HER2 expression (HER2-low) were shown to have an unfavorable prognosis. The criterion for selecting informative salivary metabolites was a multidirectional change in minimal and complete pathological responses to therapy compared to healthy controls. Thus, prognostically favorable signs were a decrease in the concentration of urea below 7.5 mmol/L (OR = 1.921; 95% CI 1.061–4.270; p = 0.0342), a decrease in the area of the absorption band at 2957 cm⁻¹ below 24 (OR = 3.875; 95% CI 1.160–12.70; p = 0.0003), and an increase in the concentration of cancer antigen CA27.29 above 3 U/L (OR = 2.138; 95% CI 1.021–7.273; p = 0.0343) and CA-15-3 above 39 U/L (OR = 3.896; 95% CI 1.062–14.07; p = 0.0072). With a simultaneous increase in both CA27.29 and CA15-3, the probability of a complete response to therapy increased (OR = 4.288; 95% CI 1.056–17.09; p = 0.0013). Multivariate analysis showed that an independent prognostic indicator, along with the expression status of HER2, estrogen receptors, differentiation degree, BMI, and menopause status, was the concentration of CA15-3 in saliva (AUC = 0.789, 95% CI: 0.737–0.842, p = 0.0001). Identifying new markers will help physicians formulate treatment plans tailored to a patient’s individual risk factors, leading to increased survival and improved quality of life. Full article

Boswellic acids (BAs), the major bioactive constituents of Boswellia serrata oleo–gum resin, exhibit well-documented anti-inflammatory and antioxidant activities, which correspond to their healing effects in arthritis, inflammatory bowel disease, asthma, metabolic syndrome, liver disorders, and certain cancers. However, their therapeutic potential is hindered by their poor aqueous solubility, low intestinal absorption, extensive metabolism, and overall low oral bioavailability. This review provides a comprehensive analysis of conventional Boswellia serrata products and advanced drug delivery systems designed to enhance the biological performance of BAs. We summarize recent developments in formulation strategies, including phytosomes, micelles, self-emulsifying drug delivery systems, solid lipid particles, polymeric nanoparticles, hydrogels, cyclodextrin complexes, metal-based nanocarriers, and hybrid delivery platforms. Available in vivo and cellular studies are critically evaluated, with a focus on disease-specific outcomes. Results indicate that emerging formulation technologies significantly increase the oral absorption, systemic exposure, and biological effectiveness of BAs. However, despite promising preclinical data, challenges remain regarding the standardization of Boswellia extracts, the stability of novel formulations, their safety, and limited clinical evaluation. By comparing the advantages and limitations of conventional preparations with modern drug delivery systems, this review outlines the most effective strategies to enhance the bioavailability of BAs and highlights future research directions for their translational development. Full article

Background/Objectives: Preclinical studies of head and neck squamous cell carcinoma (HNSCC) commonly use subcutaneous heterotopic (flank) tumor models for simplicity; however, orthotopic models may better reflect the native tumor environment. Direct comparisons of the tumor immune microenvironments (TIME) and tumor-draining lymph nodes (tdLNs) between these models remain limited. Better understanding of site-specific immune differences could improve model selection and interpretation of translational HNSCC studies. Methods: ROC1 tumors were established in murine heterotopic and orthotopic sites, followed by assessment of tumor growth kinetics, survival, and the tumor microenvironment. Immune composition of tumors, blood, tdLNs, and spleen was evaluated at three tumor progression timepoints using multiparameter spectral flow cytometry. Results: Heterotopic and orthotopic tumor models showed similar growth kinetics and survival. Immune profiling revealed increased infiltration of CD3⁺ T-cells, natural killer (NK) cells, and myeloid populations in both models. Heterotopic tumors were enriched in dendritic cells (DCs), plasmacytoid DCs, and monocytic myeloid-derived suppressor cells (M-MDSCs), whereas orthotopic tumors showed increased macrophages, granulocytic MDSCs, and M-MDSCs. Despite temporal variation, both TIMEs were dominated by macrophages, DCs, and CD3⁺ T-cells. Late-stage heterotopic tumors contained more CD4⁺ T-cells. Reduced T-cell cytotoxicity (PD-1, CD107a) and increased immune checkpoint expression across myeloid cells indicated an immunosuppressive TIME. Systemically, effector cells were preserved despite suppressive cell trafficking, and tdLNs in both models exhibited immunosuppressive PD-L1 expression. Conclusions: Heterotopic and orthotopic ROC1 tumors share key immune features, but site-specific differences in the TIME and tdLNs reveal tissue-dependent regulation. These local effects align with systemic changes, supporting global tumor-associated immunosuppression. Full article

The phenotypic plasticity of epithelial cells along the epithelial–mesenchymal (E-M) axis, or epithelial–mesenchymal transition (EMT), is a critical aspect of tumour progression and therapeutic resistance. During EMT, epithelial cells gradually acquire mesenchymal traits, facilitating vital functions in embryogenesis, wound healing, fibrosis, and tumour metastasis. This review article investigates the potential interplay between hyperglycaemia-induced metabolic stress and EMT in the context of therapeutic resistance. The study examines a complex, multifaceted network of molecular mechanisms regulating EMT, including specialised transcription factors and signalling pathways as well as growth factors, integrins, and matrix metalloproteinases in various epithelial carcinomas. Emerging findings have demonstrated the existence of EMT hybrid states along the continuum, possessing heightened metastatic potential and distinctive metabolic signatures that play critical roles in the development of therapeutic resistance in cancer cells. Hyperglycaemia has been particularly highlighted for its potential to promote EMT-driven therapeutic resistance through various interconnected mechanisms. Elevated glucose levels induce the increased production of reactive oxygen species (ROS), activation of EMT-promoting transcription factors, and a metabolic shift towards glycolysis. This hyperglycaemic stress involves upregulation of glucose transporters and glycolytic enzymes, creating feed-forward loops that support drug efflux mechanisms and help maintain the mesenchymal phenotype. Clinical data also indicate that hyperglycaemia in OSCC patients is associated with more advanced tumour stages, more extended hospital stays, less effective treatments, and higher rates of local recurrence and distant metastasis. Overall, these insights reveal a deleterious feed-forward loop in which hyperglycaemia promotes EMT-driven therapeutic resistance, with the strongest clinical evidence in oral squamous cell carcinoma (OSCC) and supportive data from pancreatic and breast cancers. Although glycaemic control represents a promising low-risk adjunctive approach, its clinical benefit remains to be validated in prospective interventional studies. Full article

Objectives: This study aims to describe a rare case of oral metastasis from small-cell neuroendocrine carcinoma originating from the lung and to perform a systematic review of the cases reported in the literature. Methods: We present the case of a patient with oral metastasis from small-cell neuroendocrine carcinoma of the lung. The patient presented at the clinical examination with severe pain in the attached gingiva in the 3.5 region, extracted one month earlier, despite prolonged antibiotic therapy. A systematic review of the literature was conducted using the PubMed, Scopus and Web of Science databases, in accordance with the PRISMA 2020 guidelines for systematic reviews. Results: A biopsy of the affected area was performed. The histological and immunohistochemical analysis revealed a fragment with features compatible with a secondary lesion with probable origin from the lung. In addition, a review of the existing English-language literature was carried out and revealed a total of six cases of oral metastasis. Conclusions: Oral metastases from small-cell neuroendocrine carcinoma are rare but have been reported in the literature. The gold standard for diagnosis remains histological examination. Full article

Background: The optimal role of induction chemotherapy (IC) in the management of oral cavity squamous cell carcinoma (OCSCC) remains controversial. This study compared oncologic outcomes between IC followed by surgery and concurrent chemoradiotherapy (CCRT) and upfront surgery followed by adjuvant CCRT. Methods: We retrospectively analyzed 98 patients with OCSCC treated between 2011 and 2017. Overall survival (OS), cancer-specific survival (CSS), and local control (LC) were evaluated using Kaplan–Meier survival analysis and Cox proportional hazards models to identify prognostic factors. Results: Fifty patients received IC and 48 underwent upfront surgery. With a median follow-up of 77.8 months, no significant differences in OS, CSS, or LC were observed between treatment groups (OS: HR 1.31, p = 0.415; CSS: HR 1.36, p = 0.421; LC: HR 1.29, p = 0.475). Positive surgical margins independently predicted inferior OS, CSS, and LC, while extracapsular spread was independently associated with inferior CSS. Although tumor downstaging was frequently observed after IC, it did not translate into survival benefit. Conclusions: IC followed by surgery was associated with no statistically significant differences in oncologic outcomes compared with upfront surgery followed by adjuvant CCRT. Prognosis was primarily determined by pathological risk factors rather than treatment sequence. Full article

Objective: This study aimed to assess whether older American adults with multimorbidity are at higher risk of becoming edentate over time. Methods: We used data from three waves of the Health and Retirement Study (HRS), a longitudinal survey of older American adults aged 50 years and over. Data on multimorbidity was from 2012, while data on complete tooth loss was from 2018. Multimorbidity included five common and serious conditions, namely diabetes, heart conditions, lung diseases, cancer, and stroke. Socioeconomic factor was indicated by total wealth in 2006; behaviour was indicated by smoking in 2012. We used Structural Equation Modelling (SEM) to assess the relationship between multimorbidity in 2012 and complete tooth loss in 2018. Participants with complete tooth loss in 2012 were excluded from the analysis. Results: Among 6286 participants with complete data across all three waves, each additional chronic condition in 2012 was associated with 1.30 times higher odds of edentulism in 2018 (95% CI: 1.12, 1.52). In the SEM, multimorbidity in 2012 was positively associated with being edentate in 2018 (estimate: 0.01, 95% CI 0.01, 0.02); smoking and wealth were also significantly associated with edentulism. Wealth and smoking were also associated with multimorbidity. Conclusions: Older adults with multimorbidity appear to have a higher probability for becoming edentate. The findings highlight the need for oral health promotion activities for those with multimorbidity. Full article

Rationale: Oral squamous cell carcinoma (OSCC) carries a poor prognosis despite advances in multimodal therapy. Nanomedicine represents a compelling strategy to enhance targeted drug delivery and improve therapeutic outcomes. Here, we investigated sEV-mediated delivery of curcumin as a novel therapeutic approach for OSCC. Methods: Small extracellular vesicles (sEVs) were isolated from Jurkat cells by size-exclusion chromatography and loaded with curcumin via sonication to generate JCsEV. Functional effects were assessed in vitro using wound healing, transwell invasion, and metabolic activity assays across multiple cancer cell lines. Therapeutic efficacy in vivo was evaluated in the 4-nitroquinoline 1-oxide (4-NQO) immunocompetent murine model of oral carcinogenesis. Female C57BL/6J mice received intraperitoneal treatment for four weeks with PBS, free curcumin, unloaded JsEV, or JCsEV. Tumor number, tumor burden, and body weight changes were assessed at the experimental endpoint. Results: In vitro, JCsEV significantly inhibited tumor cell migration, invasion, and metabolic activity compared with controls (p < 0.05). In vivo, treatment with JCsEV significantly reduced tumor number and tumor burden in the 4-NQO model (p < 0.01). In addition, body weight loss was reduced in JCsEV-treated mice compared with controls. Conclusion: sEV-mediated delivery of curcumin effectively suppresses tumor progression in experimental OSCC. These findings establish proof-of-concept for sEV-based nanomedicine as a therapeutic strategy for OSCC and provide a compelling rationale for further translational investigation of sEVs as drug delivery platforms. Full article

The human microbiota, comprising bacteria, fungi, and viruses, primarily resides in the gut, skin, and oral and nasal cavities. The gut microbiota represents the largest and most functionally relevant microbial community, playing a crucial role in digestion, metabolism and immunity. Microbiota composition and diversity have been associated with several diseases such as cancer, affecting drug efficacy, toxicity and clinical outcome. Interactions between the gut microbiota and the host immune system may contribute to the aetiology and progression of childhood acute lymphoblastic leukaemia (ALL). In this review, we summarized the general features of the gut microbiota in cancer patients and its specific role in aetiology, treatment and prognosis of paediatric ALL. Profiling the gut microbiota may help to shed the light on the mechanism of onset and to support the development of personalized treatment strategies and follow-up in children with ALL, contributing to precision medicine. Full article

Introduction: Chinese seniors in North America represent a growing population, and Traditional Chinese medicine (TCM) continues to play an important role in their health practices; however, TCM use has not been comprehensively synthesized from an immigrant perspective in North America. The purpose of this scoping review is to explore the use of TCM by Chinese seniors in Canada and the United States of America (USA). Methods: This scoping review is written in accordance with PRISMA guidelines. PubMed, PsycINFO, CINAHL, AgeLine, ERIC, ProQuest, Nursing and Allied Health Database, PsycARTICLES, Sociology Database, and Education Research Complete were selected for the literature search, which was conducted in August 2025. Articles were included if they investigated the use of any form of TCM among Chinese seniors aged 65 years or older living in the USA and Canada, and were published in an English-language peer-reviewed journal. Results: Twenty-four studies were included in this review, with a total sample size of 7288. The findings indicated that, in the majority of the included studies, over half of the Chinese seniors used some form of TCM. TCM therapies included over-the-counter herbal products, TCM-based physical activities, TCM practitioner consulting, and TCM food practices and therapies. Use of TCM among Chinese seniors was related to musculoskeletal symptoms, cardiovascular symptoms, mental health, severe acute respiratory syndrome prevention, cancer screening, and oral health. Chinese seniors tend to integrate TCM with Western medicine in their healthcare practices. Several factors from individual, familial, and community levels influenced Chinese seniors’ use of TCM. Conclusions: Future research should investigate the integration of TCM with Western healthcare, the training of healthcare providers to improve their understanding of TCM, and the underlying mechanisms of TCM products. Full article

Iron deficiency (ID) is the most prevalent nutritional disorder worldwide, affecting diverse populations including children, women of reproductive age, older adults and patients with chronic conditions. Oral iron supplementation remains the cornerstone of treatment, together with management of the underlying causes. However, conventional ferrous and ferric salts are often associated with gastrointestinal side effects, poor adherence and limited efficacy, especially in inflammatory settings due to hepcidin-mediated absorption blockade. This review summarizes iron absorption physiology, limitations of traditional oral therapies, and the potential benefits of iron protein succinylate (IPS), a ferric complex bound to succinylated casein. IPS provides pH-dependent release and contains succinic acid, which may enhance absorption while reducing gastrointestinal adverse events. Clinical studies indicate that IPS achieves hematologic outcomes comparable or superior to standard oral salts, fewer gastrointestinal effects and better tolerability. These properties make IPS suitable for patients who do not tolerate or respond adequately to conventional therapy. Special attention is given to chronic inflammation, pregnancy, cancer, or gastrointestinal disorders, where oral iron often fails due to impaired absorption or poorer tolerance. Practical recommendations are included to optimize supplementation through dosing strategies and tailored approaches. Overall, IPS offers an effective, better-tolerated alternative to conventional oral iron therapy. Full article