Search Results (72,671)

Background and Objectives: Pediatric-onset metabolic bone diseases, including osteogenesis imperfecta (OI), hypophosphatemic rickets (XLH), hypoparathyroidism, and McCune–Albright syndrome (MAS), require lifelong follow-up because of persistent skeletal fragility, biochemical abnormalities, and functional morbidity extending into adulthood. However, evidence regarding structured transition from pediatric to adult care in these rare disorders remains limited. This study evaluated one-year outcomes of a multidisciplinary transition program for adolescents and young adults with rare metabolic bone diseases. Materials and Methods: This retrospective cohort study included 20 patients aged ≥17 years who underwent evaluation through a structured transition pathway consisting of multidisciplinary team meetings, a joint pediatric–adult transition clinic, and subsequent follow-up in adult endocrinology. Demographic, clinical, treatment, and transition-related data were extracted from medical records. The primary outcome was successful transition, defined as at least one adult endocrinology visit within 12 months. Secondary outcomes included attendance at the transition clinic, follow-up continuity, and treatment modifications. Results: All patients underwent multidisciplinary evaluation, and 85% attended the joint transition clinic. Successful transfer to adult endocrinology was achieved in 90% (18/20), while regular follow-up during the first year was maintained in 75%. Retention was highest in patients with OI, MAS, XLH, vitamin D-dependent rickets, and DiGeorge syndrome (100%). Greater variability was observed in postoperative and primary hypoparathyroidism. Treatment adjustments were required in 40% of patients, including optimization of phosphate/calcitriol replacement and reassessment of bisphosphonate or burosumab therapy. Three patients were lost to follow-up. No acute transition-related complications were observed. Conclusions: In this small exploratory cohort, implementation of a structured multidisciplinary transition pathway was feasible and was accompanied by high transfer and one-year retention rates. Observed differences across diagnostic subgroups should be interpreted cautiously, and larger multicenter comparative studies are needed to evaluate the effectiveness of structured transition frameworks. Full article

Background: Gender medicine is an emerging approach that recognizes how biological sex, gender identity, and sociocultural roles influence health and disease. These factors can significantly affect prevention, screening, diagnosis, and treatment outcomes. In oncology, accumulating evidence highlights sex-based differences in cancer incidence, therapeutic response, and treatment-related adverse events. A comprehensive gender-based approach should also address the specific needs of sexual and gender minority (SGM) populations. Based on the existing literature and the authors’ expertise, this perspective paper provides an overview of this topic, emphasizing its importance, discussing current challenges, and proposing potential future directions for research and clinical practice. The literature discussed in this article was selected through a narrative, rather than a systematic, approach and is intended to provide the scientific context supporting the authors’ perspective and interpretation of the current evidence. Methods: To investigate gender differences in oncology regarding epidemiological data, we queried the AIRTUM and GLOBOCAN databases. Furthermore, we conducted a bibliography search of scientific papers by querying PubMed/MEDLINE to explore gender differences, in particular regarding treatments. The database was searched by looking for papers published between 1 January 2022 and 31 December 2025. Results: Cancers affecting both sexes show higher incidence and mortality rates in men, a trend observed worldwide and confirmed by national data. However, important sex-related differences also emerge in treatment response. Women appear to derive a smaller survival benefit than men from immunotherapy alone but may experience greater benefit when immunotherapy is combined with chemotherapy. These differences may be explained by distinct molecular mechanisms underlying antitumor immune responses in males and females. Furthermore, women experience higher rates of treatment-related toxicities, likely due to sex-specific differences in pharmacokinetics and pharmacodynamics. Conclusions: Integrating sex and gender perspectives into oncology is essential for advancing personalized medicine and improving patient care. Understanding biological differences can help optimize treatment selection and dosing strategies, thereby enhancing efficacy while minimizing adverse effects. At the same time, addressing gender-related factors may improve psychosocial support, patient well-being, and treatment adherence. Achieving these goals requires coordinated efforts, including sex-disaggregated research, gender-sensitive clinical protocols, and healthcare policies aimed at reducing gender disparities in cancer care. Full article

Hypertension is a prevalent disorder that results in millions of deaths worldwide. In this regard, timely diagnosis and effective treatment are paramount for maintaining optimal blood pressure levels in the early stages of the disease. The objective of the present study was to synthesize and assess the effect of peptides derived from chia seeds that had undergone fermentation with Lacticaseibacillus paracasei strain 2501 (hereinafter referred to as LPDP, i.e., L. paracasei-derived products from this fermentation) on the angiotensin-converting enzyme (ACE) and the spontaneously hypertensive rat model (SHR). LPDP exhibited competitive inhibition, as evidenced by the identification of seven peptides in the <1 kDa fraction by HPLC-QToF-MS. The LPDP exhibited an IC₅₀ of 11.1 μg/mL on ACE. The oral administration of 50 mg/kg body weight (BW) to SHR over a 14-day period resulted in a significant reduction in systolic pressure from 152 to 87 mmHg, accompanied by a substantial decrease in diastolic pressure from 117 to 74 mmHg. It is noteworthy that doses of 500 mg/kg BW led to a significant reduction in systolic pressure, from 154 to 68 mmHg and diastolic pressure, from 117 to 42 mmHg under identical experimental conditions. The hematological profiling of the assayed animals revealed that LPDP has no adverse effects at the cellular or biochemical level. These findings indicate the anti-hypertensive properties of LPDP and its possible application in the treatment of blood pressure. Full article

In Singapore, indoor space spraying, such as ultra-low-volume (ULV) treatment, is used to control adult mosquitoes during vector-borne disease outbreaks. This study assessed the efficacy of Mirakn^® GX, a pyrethroid-based insecticide formulation combining d,d-trans-cyphenothrin with desiccated carbon dioxide as a propellant. The implications of these findings for operational use will be discussed. Mirakn^® GX was evaluated against confined field and laboratory strains of Aedes aegypti, Ae. albopictus and Culex quinquefasciatus under semi-field conditions, following World Health Organization (WHO) guidelines. This study was conducted within an occupied residential apartment unit. An additional evaluation focusing on Ae. aegypti, designed to mimic operational practice, was performed using a reduced exposure duration of 10 min. At an application rate of 1 g/m³ with 60 min exposure, 100% knockdown and 99.79–100% mortality were observed across all three mosquito species. A shortened 10 min exposure also resulted in complete knockdown and mortality in both laboratory and field strains of Ae. aegypti, supporting operational feasibility. Under semi-field conditions, the insecticide formulation showed good penetration into enclosed spaces, indicating its potential use for scenarios where timely management of indoor adult mosquitoes is required, including during outbreaks to kill infected mosquitoes. Full article

Background: Obstructive sleep apnoea (OSA) is increasingly associated with earlier onset and accelerated trajectories of neurodegenerative change. Mechanistically, this relationship is thought to reflect convergent pathways spanning intermittent hypoxia. Biomarker profiling offers a pragmatic route to interrogate these processes in vivo, providing quantitative indices for risk stratification and for monitoring the biological response to OSA therapy in the context of cognitive decline prevention. Objectives: The present study undertakes a scoping review on the mechanistic links between OSA and neurodegeneration, as well as the utility of biomarkers for risk stratification and monitoring efficacy of treatment to mitigate cognitive decline. Methods: A literature search was conducted using PubMed, Scopus, Embase and Cochrane from January 2000 to February 2026. Search terms included “Obstructive sleep apnoea”, “Continuous Positive Airway Pressure”, “Uvulopalatopharyngoplasty”, “Biomarkers”, “Genomics”, “Alzheimer Disease” and “Parkinson Disease”. We included all studies that analysed biomarker changes in OSA patients and/or the effect of CPAP on biomarkers. Studies with only cognitively impaired cohorts, editorials, opinion pieces, conference abstracts, non-human studies, and non-English studies were excluded. Results: A total of 59 unique studies were included. Forty of them analysed biomarkers involved in the pathophysiology behind neurodegeneration in OSA patients, while 26 described the changes in biomarkers post therapy. Notably, 15 studies were included in both aspects. Lastly, eight studies explored novel applications of multiomics technologies. Full article

Background: Alcoholic liver disease (ALD) represents a major global health burden, encompassing a spectrum of hepatic abnormalities ranging from steatosis to cirrhosis and hepatocellular carcinoma. Laennec, a human placenta-derived hydrolysate, was evaluated for its therapeutic effects on alcohol-induced fatty liver in an experimental animal model. Methods: Animals were pretreated with alcohol for 2 weeks, followed by the co-administration of alcohol and Laennec for 4 weeks. The study included four groups: normal control, alcohol-only, and low- and high-dose Laennec-treated groups. Results: Alcohol administration significantly elevated the serum ALT levels (3.17-fold vs. control), indicating hepatocellular injury, whereas Laennec treatment reduced the ALT levels in a dose-dependent manner. The AST levels increased in the alcohol-only group, although the change was not statistically significant; however, the AST levels decreased in the low-dose Laennec-treated groups. The AST/ALT ratio showed significantly dose-dependent recovery in the high-dose group. Laennec treatment attenuated hepatic lipid accumulation and inflammation, with the most pronounced effects observed in the high-dose group. Regarding alcohol-metabolizing enzymes, Laennec exhibited an inhibitory effect on alcohol-induced ADH activity, with no significant effect on ALDH. CYP2E1 activity was suppressed in a dose-dependent manner following Laennec administration. No significant changes were observed in the GPx activity. Additionally, high-dose Laennec significantly restored the catalase and STAT3 (Ser727) phosphorylation levels. Histopathological analysis (H&E staining) demonstrated marked reductions in lipid droplet accumulation and inflammatory cell infiltration in Laennec-treated groups compared to the alcohol-only group. Conclusion: These findings suggest that Laennec exerts hepatoprotective effects against alcohol-induced liver injury and steatosis, as evidenced by improvements in biochemical markers, enzyme activity, and histological features. Full article

Background/Objectives: Due to its rapidly aging population, lung cancer is expected to become the second most common and deadliest cancer in Japan. Although surgery is the primary treatment for early-stage non-small cell lung cancer (NSCLC), advances in radiation therapy technology mean that stereotactic body radiation therapy (SBRT) is also a viable option for elderly patients with various underlying health conditions. Methods: We conducted a retrospective analysis to evaluate the outcomes of SBRT in 50 consecutive elderly patients (37 of whom were aged 80 and older) with early-stage peripheral NSCLC (Tis~T2aN0M0), who were treated with SBRT at our hospital and received a total dose of 55 Gy in four fractions. Results: The three-year overall, disease-free and cause-specific survival rates for all patients were 73.2%, 88.5% and 91.4%, respectively. For patients aged 80 years and older, these rates were 77.5%, 90.6% and 91.4%, respectively. There was no local recurrence. Hematogenous metastases were observed in four patients. However, hilar and subcarinal lymph node metastases developed in only one patient. Grade 2 pneumonitis and chest wall injuries (CWIs) were observed in two and five patients, respectively. Patients with larger tumors had a significantly higher incidence of chest wall injuries. Conclusions: SBRT at a total dose of 55 Gy in four fractions can achieve safe and satisfactory outcomes for early-stage peripheral NSCLC, even in patients aged 80 years and older. While CWIs were limited to Grade 2, attention to the chest wall dose is advisable when treating tumors adjacent to the chest wall. Full article

Cutaneous leishmaniosis (CL) remains a major neglected tropical disease, with current therapies constrained by toxicity, high cost, and variable efficacy. Here, we evaluated an immunochemotherapy strategy combining topical amphotericin B (AmB) with the therapeutic DNA vaccine HisAK70 in a murine model of Leishmania major infection. BALB/c mice were subcutaneously infected and treated with topical AmB cream alone, AmB plus HisAK70, or paromomycin (PM) as a reference therapy. Therapeutic efficacy was assessed through lesion progression, parasite burden in draining lymph nodes and spleen, and immunological markers associated with parasite control. Both PM and the combined AmB + HisAK70 treatment significantly reduced lesion progression and markedly decreased parasite burden compared with infected controls, demonstrating effective control of local infection and systemic dissemination. Importantly, the combination therapy enhanced the efficacy of AmB alone, supporting the beneficial contribution of vaccine-driven immune modulation to therapeutic outcome. Therapeutic efficacy was associated with reduced arginase activity in infected tissues and an increased IFN-γ/IL-4 ratio, indicative of a protective Th1-oriented immune response. Together, these findings highlight immunochemotherapy as a promising strategy for CL treatment, integrating localized topical drug delivery with targeted immune activation to improve therapeutic efficacy while potentially reducing systemic toxicity. Full article

Breast cancer is a highly heterogeneous malignancy with multiple molecular subtypes and variable treatment responses. Despite advances in endocrine therapy, HER2-targeted therapy, chemotherapy, and immunotherapy, treatment resistance and disease recurrence remain major clinical challenges. There is growing evidence that transcriptional plasticity and enhancer relinking contribute to tumor progression and treatment adaptation, highlighting the powerful role of epigenetic regulators. CREB-binding protein (CBP) and E1A-associated protein p300 (EP300) are transcriptional coactivators that regulate breast cancer enhancer activity and lineage-specific gene expression. Emerging research suggests that CBP/p300 is more of a context-dependent vulnerability point than a universal carcinogenic driver. ER-positive tumors exhibit a strong dependence on CBP/p300-mediated transcriptional programs, while the triple-negative breast cancer subgroup, including androgen receptor-positive and immunosuppressive tumors, may rely on CBP/p300-dependent signaling to maintain survival and treatment resistance. This is in contrast to their role in HER2-positive breast cancer. This review summarizes the biological functions of CBP/p300 in breast cancer and discusses subtype-specific vulnerability, biomarker-directed patient stratification, drug resistance mechanisms, rational combination strategies, and current translational challenges, emphasizing the need for precise treatment of breast cancer. Full article

Neurodegenerative diseases (NDs) such as Alzheimer’s, Parkinson’s, and Huntington’s disease are progressive and currently incurable conditions characterized by the deterioration of neuronal structure and function. Its incidence is increasing, primarily driven by global aging, and it represents a significant public health concern. Traditional therapies offer only symptomatic relief and are unable to halt or reverse the underlying neurodegenerative processes. One of the key challenges in developing effective treatments is the presence of biological barriers, such as the blood–brain barrier (BBB), which limits drug delivery to the central nervous system (CNS), namely the brain. Nanotechnology has emerged as a promising tool to overcome these obstacles. Nanoparticles (NPs), due to their small size, biocompatibility, and versatility, can be engineered to cross the BBB, protect therapeutic agents from degradation, and deliver them precisely to target sites in the brain. This work explores the current advances in lipid and polymeric-based nanoparticle (LNPs and PNPs, respectively) drug delivery systems (DDS) and their application in preclinical studies for the treatment of the NDs previously mentioned. The presented studies suggest that this strategy holds great potential, offering new perspectives and emerging strategies to improve therapeutic outcomes for NDs, and promote neuroprotection of the brain. Full article

Exosomes are 30–150 nm extracellular vesicles that convey molecular information reflecting the physiological and pathological states of their source cells. In precision oncology, they function as a non-invasive “liquid biopsy,” enabling real-time monitoring of tumor dynamics and metastasis. However, extreme biofluid heterogeneity poses significant challenges for their isolation and analysis using conventional statistical approaches. This review aims to examine how artificial intelligence (AI), specifically machine learning and deep learning, transforms complex exosomal “noise” into actionable clinical insights. AI enhances exosome isolation, enables disease-specific biomarker identification, and predicts therapeutic responses with high precision. Integrating multi-omics data and single-exosome analysis enables AI-driven models to facilitate early cancer detection and therapeutic resistance monitoring. Despite challenges related to standardization and data privacy, the convergence of AI and exosome biology is poised to transform reactive cancer treatments into a proactive, personalized medical ecosystem. This approach also provides a framework for managing other complex systemic diseases. Full article

Background: Chlorodontia is a rare condition characterized by intrinsic green discoloration of teeth. It is most often reported in association with bilirubin pigment deposition during teeth development, in cases of severe and/or prolonged neonatal hyperbilirubinemia. In extremely preterm infants, this condition may be complicated by other developmental enamel defects (DDE), such as hypoplasia or hypomineralization, linked to prematurity, systemic diseases, nutritional disturbances, and intensive care exposures. That overlap of enamel abnormalities can make diagnosis more difficult, necessitate a complex treatment plan, and increase the unpredictability of dental treatment efficacy. Case Presentation: This report presents the case of a child born at 25 weeks’ gestation with a birth weight of 910 g. Her neonatal course was complicated by, among others, recurrent episodes of hyperbilirubinemia, first neonatal (treated with phototherapy between the second and fifth day of life), and afterwards due to cholestasis from day 30 of life, with coexisting bacterial sepsis and metabolic disturbances. The available neonatal medical documentation indicated that total bilirubin level peak took place on the 40th day of life with levels approaching approximately 30 mg/dL, as well as levels of conjugated bilirubin being 19.0 mg/dL, but the exact peak values, duration, and bilirubin fractionation were not given in the patient’s discharge form. At 15 months of chronological age (11.5 months corrected age), she was referred for an assessment of abnormal morphology and green discoloration of the erupted primary incisors. Clinical examination revealed intrinsic green discoloration of the teeth, rough incisal edges and enamel breakdown on the incisal third. During follow-up, less intensity of the green pigmentation in the subsequent groups of erupted teeth was noticed. Despite excellent oral hygiene and adherence to a low-cariogenic diet, the primary first molars probably developed post-eruptive enamel loss with exposed dentin tissue. Minimally invasive management was introduced using atraumatic restorative treatment with glass-ionomer cement, combined with intensive preventive care. Conclusions: Despite the fact that, in the presented case, the diagnosis of presumptive bilirubin-related green pigmentation relies exclusively on the clinical picture and the complex neonatal medical history, it shows that, in extremely preterm infants, chlorodontia may coexist with hypomineralization or hypoplasia. This requires the introduction of dental treatment and prophylaxis, adjusted to the child’s age, to lower the risk of further complications of DDEs. Full article

Objective: Squamous cell carcinoma antigen (SCC-A) is a widely used biomarker for squamous cell cervical carcinoma and pretreatment elevation is associated with poor prognosis. Normalization during chemoradiation correlates with PET-CT response and survival. This study assessed the prognostic value of SCC-A normalization for biopsy-proven pathological response and survival outcomes. Materials and Methods: This retrospective single-center cohort study included patients with locally advanced or node-positive squamous cell cervical cancer treated with definitive chemoradiation at the Medical University Innsbruck between 2008 and 2023. Eligible patients had baseline SCC-A ≥ 2 ng/mL and at least two additional measurements within 42 days of treatment. SCC-A normalization was evaluated at predefined weekly time points. Associations with biopsy-assessed residual disease, PFS, and OS were assessed. Results: Of 186 screened patients, 83 met the inclusion criteria. Within 42 days, 70% achieved SCC-A normalization, with a median time of 21 days (IQR 19–32). Among predefined time points, normalization by day 28 was associated with reduced odds of residual disease (OR 0.14; 95% CI 0.04–0.44) and improved PFS (HR 0.28; 95% CI 0.12–0.63) and OS (HR 0.37; 95% CI 0.14–0.96), remaining independently significant after multivariate adjustments. Conclusions: SCC-A normalization during chemoradiation is a non-invasive independent biomarker of treatment response. Normalization within 28 days identifies patients at low risk of residual disease, progression, and death, supporting its use for early risk stratification and response monitoring for potential treatment adaptations. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease with limited treatment options. Here, we demonstrate that fucoxanthin (FUCO), a natural marine carotenoid, attenuates free fatty acid (FFA)-induced hepatocellular steatosis and inflammatory responses in vitro by targeting the EGR2-CD36 axis (EGR2, early growth response protein 2; CD36, cluster of differentiation 36). In FFA-induced hepatocyte models (HepG2, Hep3B, and AML12), FUCO significantly reduced lipid accumulation and inflammatory markers without cytotoxicity. Mechanistic studies revealed that FUCO specifically inhibited fatty acid uptake and transport by downregulating CD36, while triglyceride (TG) degradation remained unaffected. RNA sequencing identified EGR2 as a master regulator induced by FFA and suppressed by FUCO. Functional validation showed that EGR2 overexpression completely blocked FUCO’s lipid-lowering effects and restored CD36 expression, confirming that FUCO acts through EGR2-dependent CD36 inhibition. Bioinformatic analysis further supported EGR2-mediated regulation of CD36 via tumor necrosis factor (TNF) and sterol regulatory element-binding factor (SREBF) pathways. Collectively, our findings establish EGR2 as a critical molecular target for FUCO and provide mechanistic insights that may support its further evaluation in preclinical models for MASH therapy. Full article

Background: Chronic rhinosinusitis with nasal polyps, CRSwNP, represents one of the most clinically relevant models of type 2 inflammation in the upper airways. Its pathogenesis is not sustained by a single mechanism but by the continuous interaction between epithelial barrier damage, immune activation and tissue remodeling. Although several systemic biomarkers are currently used in clinical practice, they do not always reflect the inflammatory processes occurring directly within the sinonasal mucosa. Objective: This review discusses nasal cytology as a local and clinically accessible read-out of type 2 inflammation and epithelial barrier dysfunction in CRSwNP. Particular attention is given to the relationship between cytological patterns, underlying immune mechanisms and the use of biologic therapies. Methods: A narrative review of the literature was conducted, focusing on epithelial barrier abnormalities, type 2 inflammatory pathways, cytological phenotypes and available monoclonal antibodies. The clinical relevance of these elements was considered, with particular regard to patient stratification and therapeutic decision-making. Results: Epithelial barrier disruption promotes the release of alarmins such as TSLP, IL-25 and IL-33. These mediators activate both innate and adaptive type 2 immune responses and contribute to the persistence of mucosal inflammation. Nasal cytology allows direct assessment of the local inflammatory infiltrate and makes it possible to identify eosinophilic, mast cell-predominant and mixed eosinophil–mast cell patterns. These profiles appear to mirror different inflammatory settings. In particular, the coexistence of eosinophils and mast cells may identify patients with more severe, persistent or recurrent disease. When integrated into clinical tools such as clinical–cytological grading (CCG), nasal cytology may improve disease stratification, support follow-up and help orient biologic therapy according to the level of the inflammatory cascade predominantly involved. These cytological profiles may also support biologic treatment selection, therapeutic monitoring, and future tapering strategies by reflecting the predominant inflammatory pathway active at the mucosal level. Conclusions: Nasal cytology is a direct, reproducible and clinically useful approach for evaluating local inflammation in CRSwNP. By providing information from the mucosal site of disease, it complements systemic biomarkers and may support personalized therapeutic strategies and biologic treatment selection in CRSwNP. Full article