Background: Chronic periodontitis is a prevalent inflammatory disease. It goes beyond the oral cavity, exerting systemic immunomodulatory effects through continuous low-grade inflammation, microbial dysbiosis, and cytokine spillover. Accumulating evidence suggests that the immunological consequences of periodontitis may influence systemic immune homeostasis and alter responses to cancer immunotherapies, specifically checkpoint blockade. Objectives: This narrative review describes how periodontal inflammation induces systemic immune reprogramming. It also investigates possible effects on the efficacy of immunotherapy. Methods: The paper synthesizes current findings on molecular and cellular mechanisms linking periodontitis to immune dysfunction. It underscores the mutual signaling pathways NF-κB, STAT3, and PD-1/PD-L1 that connect oral and systemic immunity. Results: Chronic periodontal inflammation reprograms innate and adaptive immune responses. It elevates proinflammatory mediators, such as IL-1β, IL-6, and TNF-α. It alters T-cell polarization and promotes myeloid cell “training”. This process may lead to immune exhaustion, impaired antigen presentation, and treatment resistance. Preclinical and new clinical data suggest that controlling periodontal inflammation may partially reduce systemic inflammatory burden, although clinical evidence in immunotherapy-treated cancer cohorts remains limited. Conclusions: Periodontal health should be considered in the management of immunotherapy. This can facilitate new studies that integrate oral and systemic immunology. Understanding the two-way link between periodontal inflammation and systemic immune reprogramming may offer fresh opportunities for personalized immunomodulation and combined interventions.

Background: Saliva has been identified as a valuable diagnostic biofluid due to its non-invasive collection and its capacity to reflect oral and systemic biological processes. Advances in analytical chemistry, biosensing technologies, and artificial intelligence (AI)-assisted data integration have broadened the applications of salivary diagnostics. Among salivary exposome components, heavy metals such as lead, cadmium, mercury, nickel, chromium, arsenic, and aluminum serve as biologically and clinically relevant indicators of environmental exposure, toxic burden, and disease-associated molecular disorders. Methods: This structured review integrates clinical, experimental, and translational studies published between January 2020 and January 2026 that examined salivary heavy metal profiling in relation to oral health. Evidence was identified using systematic searches of PubMed/MEDLINE and supplementary sources. Studies were qualitatively assessed regarding analytical methodologies, reported concentration ranges, biological mechanisms, disease associations, and the development of digital and AI-assisted diagnostic applications. Results: Thirteen human clinical studies and six animal or in vivo investigations met the inclusion criteria. Across these studies, altered salivary metal profiles were linked to oxidative stress, inflammatory signaling, immune dysregulation, microbiome disturbances, and genotoxic markers relevant to periodontal disease, oral mucosal pathology, and the risk of oral squamous cell carcinoma. Inductively coupled plasma mass spectrometry was the predominant analytical platform, while emerging biosensor technologies showed potential for rapid detection and monitoring. Digital and AI-based approaches were identified as promising tools for integrating metallomic data with clinical and molecular biomarkers to support exposure-informed risk stratification. Conclusions: Salivary heavy metal profiling represents a biologically informative, non-invasive method for exposure-aware risk assessment in oral health. Although current clinical translation is limited by methodological variability, small cohort sizes, and the lack of standardized reference ranges, integration with digital biosensing platforms and explainable AI frameworks might facilitate scalable, precision-oriented salivary diagnostics.

Background: Endometrial proliferative lesions are common in the menopausal transition and carry a measurable risk of carcinoma. Early risk stratification may guide evaluation and follow-up. Methods: We performed a single-center retrospective study of 315 women aged 45–55 years (May 2021–May 2024) at a private clinic in Bucharest. Lesions were classified per WHO 2014 as hyperplasia without atypia, atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN), or adenocarcinoma; “advanced pathology” was defined as AH/EIN or adenocarcinoma. Clinical comorbidities and transvaginal ultrasound endometrial thickness were recorded. Associations were tested with χ²; odds were estimated with multivariable logistic regression (adjusted ORs), with a modified Poisson sensitivity analysis for adjusted relative risk. Thickness differences were compared by one-way ANOVA, and severity correlations by Spearman’s ρ. Internal validation used 1000-bootstrap resampling. Results: Hyperplasia without atypia comprised 74.6% of cases, AH/EIN 20.0%, and adenocarcinoma 5.4% (advanced pathology 25.4%). Diabetes was independently associated with advanced pathology (aOR 2.75; 95% CI 1.14–6.61; p = 0.0237), while a history of non-atypical hyperplasia was inversely associated (aOR 0.31; 95% CI 0.13–0.72; p = 0.0068). Obesity showed a borderline association (aOR 1.79; 95% CI 0.98–3.26; p = 0.058), and long-term oral contraceptive use also approached significance (aOR 0.42; 95% CI 0.18–1.00; p = 0.051). Endometrial thickness increased stepwise with histopathological severity (ANOVA p < 0.0001; η² = 0.44) and correlated with ordered severity (ρ = 0.634). The multivariable model showed moderate discrimination (AUC 0.68; optimism-corrected 0.66) with acceptable calibration (slope 0.92; Hosmer–Lemeshow p = 0.052) and overall accuracy (Brier 0.18). Conclusions: In perimenopausal abnormal bleeding, metabolic comorbidities—especially diabetes—together with increased endometrial thickness identify women at higher risk of AH/EIN or carcinoma. Histopathology remains the diagnostic reference. The model can aid clinical prioritization but requires external validation and should not be used as the sole basis for decisions.

Background: Psychological distress is increasingly recognized as an important determinant of health-related quality of life (HRQoL) in adults with diabetes mellitus (DM). However, data quantifying this burden in Eastern European populations remains limited. Objectives: This study aimed to assess psychological distress—defined as anxiety, depressive symptoms, or perceived stress—and HRQoL among Romanian adults with DM compared with healthy controls, and to explore potential differences between diabetes subtypes. Methods: A cross-sectional study was conducted, including 400 adults (201 with DM and 199 healthy controls). Psychological distress was evaluated using the State–Trait Anxiety Inventory (STAI-Y1, STAI-Y2), Beck Depression Inventory (BDI), and Holmes–Rahe Stress Scale, while HRQoL was assessed using the EQ-5D Visual Analogue Scale. Group comparisons were performed using appropriate parametric or non-parametric tests, with additional multivariable analyses adjusting for age, sex, and body mass index. Results: Adults with diabetes exhibited significantly higher levels of anxiety, depressive symptoms, and perceived stress, and lower HRQoL, compared with controls (all p < 0.001). These differences remained statistically significant after adjustment for age, sex, and body mass index. Exploratory analyses revealed no statistically significant differences between diabetes subtypes, although subgroup comparisons were limited by sample size. Conclusions: Psychological distress is highly prevalent among Romanian adults with DM and is associated with poorer self-perceived health-related quality of life. The results support the relevance of incorporating systematic psychosocial assessment into routine diabetes care.

Background: Hypertension and psychological distress often coexist, though evidence from Eastern Europe is still limited. Stress, anxiety, and self-efficacy influence blood pressure control and treatment adherence. Their effect on hypertension prevention and treatment has not been systematically evaluated in Romania. Aim: This study evaluated the associations between stress, anxiety, and self-efficacy in Romanian adults with and without hypertension to identify modifiable psychological factors relevant for integrated cardiovascular management. Methods: A retrospective case–control study was conducted among 215 adults, including individuals with hypertension and normotensive controls. Participants completed validated questionnaires assessing stress vulnerability, perceived stress, state and trait anxiety, self-efficacy, and Type A behavior, together with demographic and occupational data. Results: Hypertensive participants reported higher stress vulnerability, perceived stress, and anxiety, as well as lower self-efficacy, compared with controls. Type A behavior showed no association with hypertension. These differences remained consistent after accounting for demographic characteristics. Conclusions: Hypertension in Romanian adults is associated with a distinct psycho-emotional profile characterized by elevated stress and anxiety and reduced self-efficacy. Type A personality showed no association. The results emphasize the importance of recognizing and addressing modifiable psychological determinants in hypertension care. Integrating psychosocial assessment with personalized interventions, including mindfulness-based approaches, digital health support, and nurse-led telemonitoring, could improve treatment adherence, reduce emotional burden, and contribute to overall cardiovascular health. This region-specific evidence supports expanding hypertension management to include psychological care alongside standard medical approaches.

Microbiome dysbiosis has become recognized as an important interface connecting environmental exposures to chronic inflammatory and degenerative diseases. Although prior research has largely considered heavy metals as biomarkers of exposure and toxicity, their function as ecological modulators of host-associated microbial communities remains underexplored. The oral cavity is a distinct exposome–microbiome interface where environmental, behavioral, and intraoral metal sources converge and interact with structured biofilms and mucosal immunity. This review adopts an ecological systems perspective, interpreting chronic low-dose exposure to metals such as cadmium, lead, mercury, nickel, chromium, arsenic, and aluminum as a sustained selective force on oral microbial networks. A resilience–threshold model is proposed in which cumulative metal pressure progressively diminishes microbial community stability, alters network topology, and drives transitions toward persistent dysbiosis. These modifications are further reinforced by oxidative–inflammatory feedback loops at the host–microbiome interface, facilitating a self-sustaining ecological imbalance. Sketching on insights from microbial ecology, environmental toxicology, and host response biology, this review presents a framework that links metallomic patterns to microbial restructuring, redox imbalance, immune activation, and regulatory adaptation. The analysis emphasizes ecological perturbations from stable dysbiotic states and identifies key methodological limitations that currently restrict causal inference. By conceptualizing heavy metals as active ecological drivers rather than passive exposure indicators, this work establishes a foundation for understanding microbiome-mediated disease susceptibility within an exposome-informed systems biology framework.