Francesco Franco

Background/Objectives: With the growing number of cancer survivors receiving long-term endocrine therapy, understanding its potential effects on oral and periodontal health is of increasing clinical relevance. This systematic review aimed to synthesize current evidence on the impact of hormone therapies used in cancer treatment on periodontal status. Methods: A comprehensive literature search was conducted across the Medline, Web of Science, and Scopus databases to identify observational studies published up to June 2025 that evaluated the effects of endocrine therapy on periodontal parameters and tooth loss in cancer patients. Results: Thirteen studies met the inclusion criteria, twelve involving breast cancer patients and one prostate cancer. Third-generation aromatase inhibitors (AIs) were the most frequently studied agents, either alone or in comparison with tamoxifen. Most studies reported that AI therapy was associated with a higher prevalence of severe periodontitis, increased bleeding on probing and more severe alveolar bone loss compared to healthy controls. In contrast, tamoxifen appeared to have a comparatively milder impact on periodontal health. The single study on prostate cancer patients undergoing androgen deprivation therapy similarly indicated a higher prevalence of periodontitis with respect to controls. Conclusions: These findings suggest a potential link between endocrine therapy and periodontal status deterioration, particularly with AIs. This review highlights an important yet often neglected aspect of survivorship care and emphasizes the need for routine periodontal assessment and interdisciplinary collaboration in the management of patients undergoing hormone therapy for cancer.

This study aimed to investigate the effect of enamel matrix derivatives (EMD) on the early healing biomarkers’ expression following flapless treatment. Thirty-eight patients with residual deep intrabony defects after steps 1 and 2 of periodontal therapy were randomly assigned to the test (flapless with EMD) or control group (flapless alone). Periodontal parameters were recorded at baseline and 6 months after treatment. Gingival crevicular fluid (GCF) was collected at baseline and 2 weeks after treatment to quantify the levels of biomarkers related to epithelial healing (epidermal growth factor, EGF), connective tissue healing (matrix metalloproteinase-8 [MMP-8], fibroblast growth factor [FGF], transforming growth factor-β [TGF-β]), and bone formation (osteoprotegerin [OPG]). The test group showed a significant reduction in MMP-8 levels (p = 0.039), along with significant increases in EGF (p < 0.01), FGF (p < 0.01), and OPG (p < 0.01). The control group demonstrated a significant decrease in MMP-8 (p = 0.010). No significant changes in TGF-β levels were observed in either group. At 6 months, the test group exhibited significantly greater reductions in probing pocket depth and clinical attachment level compared to the control group. This study is the first to characterize the biochemical changes following flapless treatment with EMD. These preliminary findings suggest that EMD may enhance early wound healing by modulating the expression of key regenerative biomarkers.

Recurrent aphthous stomatitis (RAS) is the most common ulcerative disorder of the oral cavity, although its etiology is still unknown. The present study aimed to identify the proteomic profile associated with the RAS inflammatory process, thereby enhancing our understanding of its etiopathogenesis. We compared salivary protein profiles of RAS patients during an active episode of oral ulceration (30 patients, mean age 36.9) to those from healthy donors without a history of RAS (30 healthy subjects, mean age 37.9). Using 2D-electrophoresis and mass spectrometry (MALDI-TOF) analysis, we identified 17 proteins that were differentially expressed in the two groups. Notably, Cystatin SN (CST1) appeared to be significantly downregulated in RAS patients. These findings were validated by Western blot analysis: CST1 was detected in only 3 of the 30 RAS cases, while it was strongly expressed in all the healthy subjects. Although preliminary, our results suggest a potential role for CST1 in the etiopathogenesis of RAS. Interestingly, the relative absence of CST1 in RAS patients seems to align with some clinical and molecular features of this disease.

Background and Objectives: Despite recent advancements in treatment, children with juvenile idiopathic arthritis (JIA) continue to experience poor health-related quality of life, and data on patient and parent satisfaction with disease management remain limited. Thus, this cross-sectional study aimed to explore the factors influencing parental satisfaction with their child’s JIA care, using the juvenile arthritis parent acceptable symptom state (JA-PASS). Materials and Methods: Parents of 63 children (43 females and 20 males; mean age 12.2 ± 3.7 years) diagnosed with JIA completed the Juvenile Arthritis Multidimensional Assessment Report (JAMAR). The study analyzed JAMAR responses, along with demographic data, disease duration and activity, and current medication use, to identify clinical factors that influence JA-PASS. Results: According to the JAMAR, 55.6% of parents expressed satisfaction with their child’s current condition. In a multiple regression analysis, significant factors influencing JA-PASS included medication side effects (p = 0.033), current disease activity (p = 0.009), and the psychosocial well-being rating in the JAMAR questionnaire (p = 0.048). Conclusions: JA-PASS should be integrated into patient assessment protocols, as it provides valuable insight into parents’ perceptions of disease progression and effectiveness of therapeutic interventions.

Background/objectives: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood, leading to severe disability and negatively affecting patients’ health-related quality of life (HRQoL). The aim of this systematic review was to evaluate the adoption, reporting and assessment methodology of HRQoL in phase III clinical trials involving children with JIA. Methods: An electronic and manual search was conducted to identify primary and secondary publications of pharmacological trials conducted between 2012 and 2023. Data were extracted and recorded in duplicate. Results: A total of 222 studies were screened and 24 articles (22 primary and 2 secondary publications) were included in the review. HRQoL was not listed among the endpoints in 10 trials (45.5%), while it was a secondary endpoint in 12 trials (54.5%). The proportion of trials that did not consider HRQoL was equally relevant in both for-profit and no-profit settings (44.4% versus 50.0%), but it was higher in studies on systemic JIA compared to other JIA subtypes (62.5%), and on IL inhibitor treatment (72.7%) with respect to other disease-modifying antirheumatic drugs. Information on HRQoL was usually collected from parents/caregivers, and only three studies were categorized as “probably robust” with regard to HRQoL assessment. Conclusions: Systematic incorporation of HRQoL measures represents an urgent need in pediatric rheumatology, aiding clinicians in their decision-making in relation to treatment effectiveness and considering the children’s perspective.

Cadmium (Cd) toxicity poses a significant threat to human health and the environment due to its widespread occurrence and persistence. In recent years, considerable attention has been directed towards exploring natural compounds with potential protective effects against Cd-induced toxicity. Among these compounds, resveratrol (RV) has emerged as a promising candidate, demonstrating a range of beneficial effects attributed to its antioxidant and anti-inflammatory properties. This literature review systematically evaluates the protective role of RV against Cd toxicity, considering the various mechanisms of action involved. A comprehensive analysis of both in vitro and in vivo studies is conducted to provide a comprehensive understanding of RV efficacy in mitigating Cd-induced damage. Additionally, this review highlights the importance of phytoremediation strategies in addressing Cd contamination, emphasizing the potential of RV in enhancing the efficiency of such remediation techniques. Through the integration of diverse research findings, this review underscores the therapeutic potential of RV in combating Cd toxicity and underscores the need for further investigation to elucidate its precise mechanisms of action and optimize its application in environmental and clinical settings.

The aim of this study was to test the molecular expression profile (senescence-associated secretory phenotype; SASP) in gingival crevicular fluid (GCF) prior to surgery in relation to the distribution of clinical success of periodontal regeneration. Forty consecutive patients presenting sites with residual probing pocket depth (PPD) ≥ 6 mm and intrabony defects ≥ 3 mm were treated through a minimally invasive surgical technique. Pre-operatively, GCF was sampled for inflammatory biomarker analysis related to SASP [interleukin (IL)-1β, IL-6, and IL-12; matrix-metalloproteinases (MMP)-8 and -9]. Better or worse responders were classified depending on the achievement of a composite outcome measure at 1-year [COM; PPD ≤ 4 mm and clinical attachment gain (CAL) gain ≥ 3 mm]. Correlation analyses and logistic regression models were performed. Periodontal regeneration led to significant improvements in mean clinical and radiographic parameters. Teeth achieving COM presented significantly lower amounts of SASP factors compared with non-successful teeth. Higher CAL gain, PPD reduction, and radiographic bone fill were negatively correlated with IL-1β and MMP-8 and -9 (p < 0.001), while IL-12 showed a direct relationship with CAL gain (p = 0.005) and PPD reduction (p = 0.038). Sites expressing higher SASP expression in the GCF before periodontal regeneration achieved worse clinical and radiographic outcomes.

Identification of biomarkers could help in assessing periodontal health status and monitoring treatment outcomes. Therefore, the aim of this cross-sectional study was to identify potential innovative salivary biomarkers for the diagnosis of periodontitis using an untargeted proteomic approach. Forty-five healthy non-smoker participants diagnosed as having periodontally healthy conditions (H), severe periodontitis (P), and healthy but reduced periodontium after active periodontal treatment (T) were consecutively enrolled (15 per each group) in the study. A higher number of spots were identified in the proteome of unstimulated whole saliva collected from H and T subjects compared with P group, mainly within the range of 8–40 kDa. Protein spots of interest were analysed by MALDI-TOF-MS, allowing the identification of cystatin SN (CST1) isoform, as confirmed by Western blot. CST1 was markedly expressed in the H group, while it was absent in most P samples (p < 0.001). Interestingly, a distinct CST1 expression was observed in saliva from T patients. CST1 was negatively correlated with the percentage of pathological sites (p < 0.001) and was effective in discriminating active periodontitis from healthy periodontal status (whether H or T). Therefore, salivary CST1 may be a promising non-invasive biomarker for periodontal disease diagnosis and monitoring.

Metformin (Met) is a drug commonly prescribed in type 2 diabetes mellitus. Its efficacy is due to the suppression of hepatic gluconeogenesis, enhancement of peripheral glucose uptake and lower glucose absorption by the intestine. Recent studies have reported Met efficacy in other clinical applications, such as age-related diseases. Despite the wide clinical use of Met, its mechanism of action on muscle and its effect on muscle performance are unclear. We investigated the effects of Met combined with training on physical performance (PP) in healthy rats receiving Met for 8 weeks while undergoing daily moderate exercise. We evaluated the following: PP through graded endurance exercise test performed before the beginning of the training protocol and 48 h before the end of the training period; blood ALT, AST, LDH and CK–MB levels in order to address muscle damage; and several blood and muscle myokines and the expression of factors believed to be involved in muscle adaptation to exercise. Our data demonstrate that Met does not improve the positive effects of exercise on performance, although it protects myocytes from exercise-induced damage. Moreover, given that Met positively affects exercise-induced muscle adaptation, our data support the idea of the therapeutic application of Met when muscle function and structure are compromised.

Objectives: To test the effect of locally delivered doxycycline (DOX) administered 2 weeks prior to minimally invasive periodontal regeneration in terms of presurgical inflammatory status and cytokine expression profile in the gingival crevicular fluid (GCF). Secondary aim was to assess the early wound healing index (EHI) at 2 weeks after surgery.Background: It is hypothesized that healing after periodontal regeneration is dependent on preoperative soft tissue condition, and that local antibiotics may improve the site‐specific inflammatory status at short time.Methods: Sites associated with periodontal intrabony defects requiring regenerative surgery and showing bleeding on probing (BoP) were included. At T0, experimental sites were randomly treated with subgingival instrumentation with or without topic DOX application. After 2 weeks (T1), defects were approached by means of minimally invasive surgical technique. GCF was sampled at both T0 and T1 for inflammatory biomarker analysis. Two weeks after surgery, the EHI was evaluated (T2).Results: Forty‐four patients were included. At T1, the number of BoP+ sites was statistically significantly less in the test group (27.3% vs. 72.7%; p < .01). The total amount of interleukin (IL)‐1β (p < .001), matrix‐metalloproteinases (MMP)‐8 (p < .001), and MMP‐9 (p = .010) in the GCF significantly decreased in the test group at T1, with relevant differences compared to controls. At T2, the EHI had an average value of 1.45 ± 0.86 in the test group while in the control, it was 2.31 ± 1.43 (p = .027). A statistically significantly positive correlation was observed between the amount of IL‐1β and MMP‐9 and EHI scores.Conclusions: Within the limitations of this study, sites treated with DOX showed improved clinical and molecular inflammatory parameters before surgery, as well as soft tissue healing 2 weeks after surgery.