Search Results (2,477)

Cardiac arrest followed by cardiopulmonary resuscitation (CA/CPR) induces systemic ischemia and frequently results in acute kidney injury (AKI). The ketone body β-hydroxybutyrate (BHB) maintains mitochondrial and peroxisomal homeostasis through activation of the C/EBPβ–Pck1 axis, whereas Pck1 preserves mitoribosome integrity and mtDNA-encoded oxidative phosphorylation (OXPHOS) translation. However, it remains unclear whether this pathway is disrupted during CA/CPR-induced AKI and whether empagliflozin can restore its activity. Male C57BL/6J mice and proximal tubule-specific Pck1 conditional knockout (CKO) mice were subjected to short-duration or standard CA/CPR protocols. Empagliflozin was administered orally for 7 days before CA/CPR induction. Circulating BHB levels, renal expression of C/EBPβ and Pck1, and markers of mitochondrial, peroxisomal, and mitoribosomal abundance and function were evaluated using established methods. CA/CPR markedly reduced circulating BHB levels and suppressed the C/EBPβ–Pck1 signaling axis. These changes were accompanied by depletion of peroxisomal markers, mitochondrial regulators, and mitoribosomal components as well as increased tubular apoptosis and albuminuria. Pck1 CKO mice exhibited severe organelle dysfunction and aggravated renal injury. In contrast, empagliflozin restored BHB levels, preserved C/EBPβ and Pck1 expression, and maintained mitochondrial, peroxisomal, and mitoribosomal integrity, thereby attenuating tubular injury and albuminuria. Notably, empagliflozin treatment increased BHB, C/EBPβ, and Pck1 levels in noninjured mice without inducing organelle expansion, suggesting that Pck1 activation alone is insufficient to promote mitoribosome biogenesis under basal conditions. Collectively, these findings demonstrate that empagliflozin protects against CA/CPR-induced AKI and identify Pck1 as a key metabolic regulator linking ketone signaling to organelle resilience. Full article

Parkinson’s disease (PD) is a neurodegenerative disorder associated with gut dysbiosis and tryptophan metabolism disturbance, but the mechanisms of probiotic action are unclear. We orally administered Lactobacillus reuteri DSM 17938 live bacteria (1.0 × 10⁹ CFU/mL, 0.2 mL) or its fermentation supernatant lyophilized powder at three concentrations to MPTP-induced PD male C57BL/6J mice. Treatments increased locomotor distance and speed, elevated serum SOD and GSH, reduced MDA, TNF-α, IL-6, and IL-1β, promoted neuronal survival, and tended to increase TH expression in the substantia nigra. 16S rRNA sequencing showed that treatments altered gut microbiota composition. PD mice had increased Lactobacillus and Allobaculum but decreased Oscillospira and Helicobacter; treatments restored Oscillospira. Fecal untargeted metabolomics revealed disturbed tryptophan metabolism in PD, with elevated indoleacetic acid and reduced kynurenic acid, xanthurenic acid, indole-3-ethanol, and α-oxo-1H-indole-3-propanoic acid. Treatments significantly restored neuroprotective metabolites including kynurenic acid, xanthurenic acid, and serotonin. PICRUSt2 predicted tryptophan synthesis pathway-associated microbes (Oscillospira, Ruminococcus, Coprococcus). Treatments ameliorated motor deficits, oxidative stress, inflammation, and dopaminergic neuron death, correlating with gut microbiota modulation and accumulation of microbiota-derived tryptophan metabolites. Live bacteria showed superior antioxidant and neuroprotective efficacy compared to supernatant, likely due to sustained colonization and continuous metabolic activity. These findings suggest that targeting key tryptophan-metabolizing bacteria or their metabolites may be a potential PD therapy. Full article

Population aging, persistent oral health inequalities, and growing reliance on informal caregiving are creating new challenges for oral healthcare systems worldwide. Mobile health technologies (mHealth) are increasingly being used to support oral health promotion, self-care, monitoring, caregiver assistance, and workforce training. However, it remains unclear whether existing applications adequately address the needs of older adults and their caregivers. This narrative review examined the current landscape of mHealth applications for oral health in aging populations, with particular attention to tools supporting self-care, clinical monitoring, caregiver assistance, and primary healthcare training. Following the SANRA framework, we reviewed studies published between January 2000 and May 2026 and analyzed their functionalities, target users, usability, and the evidence supporting their development and implementation. Applications for oral health education and literacy were the most frequently reported. In contrast, relatively few tools were developed specifically for caregivers, dependent older adults, or individuals with cognitive impairment. Cultural and linguistic adaptation was also uncommon. Across categories, most applications had been evaluated primarily through usability or feasibility studies, with limited evidence regarding clinical effectiveness, long-term outcomes, or integration into routine healthcare services. Viewed in the context of the WHO Decade of Healthy Ageing 2021–2030 and the Global Strategy and Action Plan on Oral Health 2023–2030, these findings suggest that while mHealth may contribute to improving oral healthcare for older adults, important gaps remain in clinical validation, accessibility, and adaptation to diverse populations and care settings. Full article

Background/Objectives: In this study, we aimed to investigate age-specific prevalence and patterns of oral frailty among Korean adults and examine its multidimensional associations with physical and mental health and health-related quality of life, from a life-course perspective. Methods: This cross-sectional study included 4459 adults aged ≥25 years from the 2023 Korea National Health and Nutrition Examination Survey. Oral frailty was defined as the presence of ≥4 deficits across 9 clinical and behavioral indicators. Associations of oral frailty with chronic diseases, appendicular skeletal muscle mass (ASM), psychological symptoms, and health-related quality of life were examined across age-stratified cohorts (25–44, 45–59, 60–74, and ≥75 years). Results: The prevalence of oral frailty was significantly higher in older age groups (8.2% at 25–44 years to 48.5% at ≥75 years, p < 0.001). Frail participants showed significantly higher prevalence of hypertension and diabetes and lower ASM, compared with non-frail participants. Difficulty pronouncing words and toothache experience showed the strongest contributions to the overall oral frailty score (p < 0.001). Oral frailty was also significantly associated with higher perceived stress and generalized anxiety, particularly among younger adults aged 25–44 years. Health-related quality of life was consistently lower in frail participants than in non-frail participants across all age groups (p < 0.001). Conclusions: Oral frailty is a multidimensional indicator associated with systemic aging, metabolic health, psychological distress, and reduced quality of life across the life course. These findings support the need for integrated, life-course-oriented oral health interventions beginning in early adulthood to prevent functional decline and promote healthy aging. Full article

The United States is experiencing rapid population aging, making geriatric oral health an increasingly important public health and clinical concern. Older adults bear a disproportionate burden of oral diseases, including dental caries, periodontal disease, edentulism, xerostomia, and oral cancer, many of which are closely linked to chronic systemic conditions such as diabetes, cardiovascular disease, and cognitive impairment. This narrative review synthesizes current evidence on oral disease patterns and trends among older adults in the United States, with particular attention to the bidirectional relationships between oral and systemic health. It further examines the organization of oral health care delivery and financing for this population, including the roles of Medicare and Medicaid. Persistent inequities in access to preventive and restorative dental services are highlighted, especially among low-income individuals, racial and ethnic minorities, rural residents, and older adults with functional or cognitive limitations. Workforce shortages, fragmented care models, and limited integration of oral health into primary and geriatric care further exacerbate these disparities. Finally, this review identifies future directions to improve geriatric oral health, including policy reforms to expand dental coverage, integration of oral health into medical and long-term care settings, adoption of minimally invasive approaches, and strengthened interprofessional education and research. Addressing these challenges is essential to promoting healthy aging and reducing oral health disparities among older adults in the United States. Full article

Background: Infective endocarditis is a serious disease affecting cardiac tissues and may arise following episodes of transient bacteremia. Oral prosthetic pressure lesions, characterized by mucosal ulcerations, may facilitate the entry of pathogenic microorganisms into the systemic circulation. In predisposed individuals, the presence of such lesions may therefore contribute to the development of infective endocarditis. The objective of this study was to assess dental professionals’ knowledge, awareness, and self-reported clinical practices related to the possible relationship between oral prosthetic pressure lesions and infective endocarditis. Materials and Methods: A cross-sectional observational study was conducted using an anonymous online questionnaire specifically developed for this study and subjected to preliminary content validation and pilot assessment before administration. The survey was distributed online to oral health professionals working in the Italian public and private sectors; for the present analysis, only complete responses provided by licensed dental professionals practicing in Italy were included. Results: Among the 268 dental professionals analyzed, an overall limited awareness of the possible relationship between oral prosthetic pressure lesions and infective endocarditis emerged. Only 16.8% of participants reported being familiar with the most recent guidelines for the prevention of infective endocarditis. Conclusions: The findings suggest the need to strengthen continuing education, improve familiarity with current infective endocarditis prevention guidelines, and promote more structured clinical protocols for the assessment and management of prosthetic pressure lesions in patients at risk. Full article

Immune checkpoint inhibitors (ICIs) have improved clinical outcomes in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), including oral squamous cell carcinoma (OSCC). However, many patients eventually develop resistance to systemic therapy, highlighting the need for novel strategies that can restore or sustain antitumor immunity. Near-infrared photoimmunotherapy (PIT) has emerged as a tumor-selective locoregional treatment that not only induces targeted tumor cell death but also promotes antitumor immune activation through immunogenic cell death. This narrative review summarizes current evidence regarding PIT for recurrent oral cancer and explores the immunological rationale for sequential ICI–PIT–ICI therapy (ICI–PIT–ICI sequence). Within this framework, PIT-induced tumor antigen release and inflammatory activation may reinitiate elements of the cancer-immunity cycle, whereas continued PD-1 blockade may help sustain newly activated tumor-reactive T-cell responses. To illustrate this concept, we present two cases of recurrent oral cancer treated with the ICI–PIT–ICI sequence. Both patients achieved durable clinical and radiological complete responses following PIT and subsequent nivolumab continuation. Longitudinal analyses of peripheral immune surrogate markers demonstrated a biphasic temporal pattern characterized by transient increases in inflammatory markers, including neutrophil-to-lymphocyte ratio, C-reactive protein, platelet-to-lymphocyte ratio, and systemic immune-inflammation index, followed by recovery trends in absolute lymphocyte count and lymphocyte-to-monocyte ratio during continued PD-1 blockade. These observations support the biological plausibility of PIT as an immune-modulating intervention with potential immune-reprogramming effects. Although hypothesis-generating, the ICI–PIT–ICI sequence may represent a promising strategy integrating locoregional tumor destruction with systemic immune modulation in recurrent oral cancer. Further prospective studies incorporating peripheral and tissue-based immune profiling are warranted. Full article

Diabetic oral mucosal wounds exhibit impaired healing and require biomaterials with strong wet adhesion, favorable biocompatibility, and adequate mechanical stability. In this study, an in situ photocurable adhesive hydrogel (ATDS) based on sulfonated chitosan was developed for diabetic oral mucosal wound repair. ATDS exhibited a tensile strength of 50 kPa, an elongation at break of 320%, and an adhesive strength of 0.605 MPa, while also displaying a porous microstructure without obvious cytotoxicity. Compared with hyaluronic acid (HA) gel, which was completely lost by day 3, ATDS provided more durable wound coverage in the oral environment. In a diabetic rat model of oral mucosal defect, ATDS significantly accelerated wound closure, with wounds nearly completely healed by day 6, promoted re-epithelialization as early as day 3, and increased epidermis thickness by approximately 50% compared with the control group. In addition, ATDS enhanced angiogenesis and reduced the expression of the inflammatory cytokines TNF-α and IL-1β. Collectively, these findings demonstrate that ATDS effectively promotes diabetic oral mucosal wound healing through its barrier-protective, pro-angiogenic, and anti-inflammatory effects, highlighting its potential as a promising biomaterial for oral tissue engineering and regenerative applications. Full article

Macrophage membrane-coated nanoparticles (MMNPs) are an emerging class of biomimetic nanoplatforms that combine the immune-regulatory functions of macrophages with the structural versatility of synthetic nanoparticles (NPs). By retaining key membrane proteins and receptors, MMNPs exhibit natural targeting capabilities, immune interactions, and inflammatory site homing, making them promising tools for immunomodulation and targeted therapy. This review summarizes macrophage biology relevant to immune regulation and discusses how nanoparticle core properties, including size, surface charge, composition, and mechanical characteristics, influence membrane coating efficiency, stability, and biological performance. Current fabrication and characterization strategies for MMNPs are also discussed. Particular emphasis is placed on the therapeutic applications of MMNPs in inflammatory disorders, tissue regeneration, and oral and dental implant-related applications. Recent studies demonstrate that MMNPs can modulate macrophage polarization, sequester pro-inflammatory cytokines, remodel the immune microenvironment, and promote tissue repair and bone regeneration, highlighting their potential to improve implant integration and reduce inflammation-associated implant failure. Despite these promising advances, challenges remain regarding large-scale manufacturing, membrane preservation, reproducibility, and long-term biosafety. Continued interdisciplinary research in nanotechnology, immunology, and biomaterials engineering is expected to accelerate the clinical translation of MMNPs for regenerative and immunomodulatory therapies. Full article

Mitochondria regulate cellular energetics, redox balance, apoptosis, and inflammatory signaling in oral, airway, and systemic tissues. Hypoxia is a powerful modulator of mitochondrial function, with effects ranging from adaptive hormesis to overt injury. Cyclic altitude training, most often delivered as intermittent hypoxic exposure or intermittent hypoxia training (IHT), has been proposed as a strategy to improve mitochondrial efficiency and exercise performance. By contrast, obstructive sleep apnea (OSA) exposes patients to uncontrolled chronic intermittent hypoxia (CIH), a pattern increasingly linked to endothelial dysfunction, ceramide-mediated mitochondrial dysfunction, insulin resistance, systemic inflammation, oral dysbiosis, and periodontitis. This narrative review covers intermittent hypoxia, mitochondrial biogenesis, hypoxia-inducible factor signaling, OSA, periodontitis, oral microbiome shifts, nitric oxide biology, and smoke-related mitochondrial injury. Appropriately dosed IHT can increase mitochondrial biogenesis, improve mitochondrial morphology, and augment oxidative capacity through pathways involving PGC-1alpha, hypoxia-inducible signaling, mitochondrial dynamics, and reactive oxygen species-dependent hormesis. In contrast, CIH in OSA promotes oxidative stress, sympathetic activation, endothelial injury, and inflammatory signaling and is associated with worse periodontal status and altered salivary microbiome profiles. Controlled IHT and OSA-related CIH, therefore, represent opposite ends of a hypoxia continuum, and mitochondrial health connects sleep-disordered breathing, periodontal inflammation, environmental exposures, and systemic cardiometabolic risk within a single conceptual frame. Sphingolipid signaling—particularly hypoxia- and toxicant-driven ceramide accumulation—connects CIH, inhaled environmental exposures, mitochondrial fragmentation, and the development of insulin resistance. Full article

Background and Objectives: Oral health is a key but often overlooked component of healthy aging and functional wellbeing in older adults. Population aging, multimorbidity, and social determinants of health interact in order to shape oral disease patterns, particularly in primary care settings. Understanding age- and sex-specific distributions of oral diseases is essential for informing integrated public health strategies aimed at promoting healthy aging. Materials and Methods: We conducted a cross-sectional population-based analysis using the SIMEF primary care database, including 7386 adults aged 60 years and older, who were attended between January and December 2022. Oral diseases were identified using ICD-10 codes K00–K14. Prevalence estimates were calculated by life decade and sex. Associations were assessed using chi-square tests and sex-stratified analyses. Results: The overall prevalence of oral diseases was 5.2%, with a significant and progressive decline across age groups, from 6.5% in sexagenarians to 1.6% in nonagenarians (p < 0.001). The most prevalent conditions were disorders of teeth and supporting structures (2.6%, 95% confidence interval [95% CI] 2.3–3.0), dentofacial anomalies (2.2%, 95% CI 1.8–2.5), and dental caries (1.7%, 95% CI 1.4–2.0). Women showed a slightly higher prevalence of selected oral and mucosal conditions. Among older adults with oral diseases (n = 384), the most frequent comorbidities were hypertension (40.4% 95% CI 35.7–45.3), type 2 diabetes (29.2% 95% CI 24.7–33.8), and dyslipidemia (21.1% 95% CI 17.2–25.3), with marked sex-specific differences in endocrine, urinary, musculoskeletal, and mental health conditions. Conclusions: Oral disease burden in older adults decreases with advancing age but remains strongly linked to cardiometabolic and systemic comorbidities, reflecting shared risk factors relevant to healthy aging. The observed age- and sex-specific patterns underscore the need to integrate oral health into primary care and public health policies targeting aging populations, supporting comprehensive and equitable strategies for healthy longevity. Full article

The Warburg effect is better understood as regulated metabolic plasticity rather than mitochondrial failure. Many malignant cells retain functional mitochondria while increasing aerobic glycolysis, lactate production, and redox remodeling to support growth, immune escape, and adaptation to microenvironmental stress. Within the context of the cancer microenvironment, this review examines xylitol as a hypothetical metabolic modifier within a broader host-microbe-mitochondria framework. Xylitol, a five-carbon sugar alcohol, is derived endogenously through the pentose phosphate pathway (PPP) and the glucuronate–xylulose pathway, and is metabolized efficiently in humans, rats, and pigs through xylitol dehydrogenase (XDH) in hepatic mitochondria and the cytosol; whereas, it is less tolerated by obligate carnivores who lack this enzyme. Preclinical studies show that partial substitution of glucose with xylitol can reduce proliferation and glycolytic markers in oral squamous carcinoma models, and preliminary studies link xylitol to glutathione depletion, endoplasmic reticulum (ER) stress, autophagy-associated death, and altered tumor metabolomics. On the other hand, oral pathogens such as Fusobacterium nucleatum and Porphyromonas gingivalis promote tumor stemness, extracellular vesicle signaling, metastasis, and immune evasion. In addition, Streptococcus mutans, the primary cariogenic pathogen, contributes to systemic bacteremia and epithelial–mesenchymal transition. Oral and gut microbiomes modulate macrophage polarization, T cell activity, and the senescence-associated secretory phenotype (SASP), possibly promoting cancer immune evasion. The anti-adhesive properties of xylitol may limit pathogen attachment to immune cell receptors, reducing the generation of pro-tumorigenic senescent immune cells. Xylitol also offers metabolic benefits, a low glycemic index, partial insulin-independent metabolism, and potential diabetes-prevention activity that are relevant, considering the established link between metabolic disease and cancer risk. A recent study reported that higher levels of endogenous xylitol were associated with adverse cardiovascular events, but confirmation of this requires large scale prospective studies. The evolutionary dietary context of MIS 6, during which hominin populations in sub-Saharan Africa depended on polyol-rich underground storage organs, provides a biological basis for human tolerance of xylitol. As a result, we hypothesize that xylitol may be a context-dependent metabolic modifier within an integrated host–microbe–mitochondria–cancer stem cell network. Full article

Oral squamous cell carcinoma (OSCC) remains a major global health burden with limited improvement in survival rates. While traditional risk factors such as tobacco and alcohol are well established, increasing evidence highlights the role of the oral microbiome in carcinogenesis. Among microbial species, Candida albicans (C. albicans) has emerged as a potential contributor to tumor-promoting processes. Clinical studies consistently report increased fungal colonization in oral potentially malignant disorders and OSCC, with associations to disease severity and recurrence. Mechanistically, C. albicans contributes to carcinogenesis through acetaldehyde production, chronic inflammation, oxidative stress, epithelial signaling modulation, and extracellular vesicle (EV)-mediated communication. These pathways promote tumor microenvironment remodeling and epithelial transformation. However, conflicting evidence exists regarding causality, suggesting that fungal colonization may also result from tumor-associated ecological changes. From a translational perspective, C. albicans and EV-associated signatures may represent promising biomarkers and therapeutic targets, although further validation is required. This review highlights the emerging role of fungal–host interactions in OSCC and underscores their potential in microbiome-informed precision oncology. Full article

The marriage bar was a widespread rule requiring women to give up their jobs upon marriage. It is generally familiar to many as a peculiarity of Ireland’s past. However, the precise details and history of its operation are frequently misunderstood and incorrectly attributed. The bar applied culturally to most aspects of employment for many years and was not exclusive to the civil service, which was governed by legislation reinforcing the bar. After introducing the intricacies of this topic, this article takes a closer look at the cultural aspects of the bar across family, archival and oral history sources. In doing so, I frame the research as a deeply personal encounter with history. Combining oral history with manuscript sources and bookended by a personal history of the marriage bar, this article considers its impact across generations. The marriage bar is also discussed in terms of Irish culture, social class, and marital status. Finally, the adjustments and ongoing limitations experienced by Irish women in the labour market after the marriage bar was gradually eradicated are discussed. I argue that the marriage bar has had a profound socio-cultural impact on Irish society across generations; its effect has never been limited to married women. While the policy caused an incalculable loss of personal fulfilment and remuneration to generations of married women, it simultaneously stymied the promotion prospects of many single women. Full article

Foods rich in polyphenols are known to promote oral health by modifying the enamel pellicle. In doing so, they reduce bacterial adhesion, biofilm maturation, and erosion. The goal of this study was to screen local herbal drugs available in Central Europe for their potential suitability as part of a diet promoting oral health by targeting the initial stages of biofilm formation. To achieve this, an in situ study was conducted to evaluate the effects of the four polyphenol-rich herbal extracts of blackcurrant leaves, oak bark, horse chestnut leaves, and sweet chestnut leaves on early bacterial adhesion and biofilm formation on tooth enamel over an 8 h period. This research aimed to identify natural remedies that could support oral hygiene by targeting the initial stages of biofilm formation. Study Design and Experimental Procedures: Aqueous extracts were prepared by ultrasonic extraction. Eight human subjects wore bovine enamel slabs intraorally for 8 h. After 1 min of pellicle formation, the subjects rinsed with 8 mL of the extracts for 10 min, followed by intraoral exposure without food. An 8 h-exposure without rinse served as the negative control; 0.2% chlorhexidine gluconate (CHX) served as the positive control. After 8 h, bacterial adhesion and biofilm matrix formation on the enamel slabs were quantified ex vivo using DAPI/Concanavalin A staining and fluorescence microscopy. The LIVE/DEAD™ BacLight™ assay was used to assess bacterial viability. Statistical analysis was performed by the Mann–Whitney U test and Kruskal–Wallis test (p < 0.05), as well as the Bonferroni–Holm correction (p < 0.01). Results and Conclusions: The screened herbal drugs did not demonstrate a statistically significant impact on the number of adherent bacteria, suggesting that their mode of action may not directly interfere with bacterial adhesion mechanisms. However, all four extracts exhibited consistent trends toward reduced glucan formation and decreased bacterial viability. The observed inhibition of glucan formation indicates that these drugs may potentially target the enzymatic pathways responsible for polysaccharide synthesis. By disrupting glucan production, the structural integrity of the biofilm matrix might be compromised, which indirectly affects bacterial survival within the biofilm environment. Full article