Search Results (738)

Background/Objectives: Ameloblastoma is a benign odontogenic neoplasm characterized by locally aggressive behavior and frequent recurrences despite surgical treatment. It originates from odontogenic epithelium, including the cell rests of the dental lamina, remnants of the enamel organ, epithelial cell rests of Malassez, or the basal cell layer of the oral mucosa. Investigation of the etiopathogenesis of ameloblastoma has gained critical relevance due to the need for extensive surgical procedures, high recurrence rates, and its malignant potential. Accordingly, the aim of the present narrative review is to summarize current evidence regarding key aspects of ameloblastoma etiopathogenesis, with emphasis on signaling pathways, mutations, epigenetics, and epithelial–stromal interactions. Methods: An extensive literature search was conducted using the PubMed, Scopus, and Google Scholar databases, employing the keywords: “etiology”, “pathogenesis”, “molecular”, “biomarkers”, “cellular”, “epigenetic”, “mutation”, “pathway”, and “ameloblastoma”. In vitro studies, clinical studies, case reports, and narrative and systematic reviews published in English were included, without restriction on publication year. Results: Current evidence indicates that ameloblastoma pathogenesis is driven by dysregulation of multiple signaling pathways, particularly the MAPK and Sonic Hedgehog pathways, through recurrent activating BRAF and SMO mutations. In addition, alterations affecting the WNT/β-Catenin and PI3K/AKT signaling cascades, epigenetic modifications, and epithelial–stromal interactions, contribute to tumor behavior. Conclusions: Despite significant advances, genotype–phenotype correlations, mutation frequencies and coexistence, clonality, and other associations remain incompletely understood. Larger tumor cohorts and robust meta-analyses are required to clarify these associations and to leverage the development of personalized therapeutic strategies. Full article

Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome encompasses a range of Müllerian duct anomalies characterized by congenital absence of the uterus and the upper two-thirds of the vagina in young women who otherwise exhibit normal endocrine function and a 46,XX karyotype. MRKH syndrome can occur in an isolated form (type I) or in association with other congenital anomalies (type II or MURCS association), which may include renal, vertebral, auditory, and cardiac defects. It represents one of the most frequent causes of primary amenorrhea, affecting approximately 1 in every 4000–5000 women. MRKH syndrome often remains undiagnosed until a patient presents with primary amenorrhea, despite normal development of secondary sexual characteristics. Both genetic and non-genetic factors have been proposed as contributing to abnormal embryonic development, although the exact etiopathogenesis remains unclear. Imaging plays a key role in the evaluation of genital tract anomalies, allowing non-invasive and comprehensive assessment. Alongside physical examination and pelvic ultrasound, pelvic MRI is essential for identifying the presence of rudimentary uterine tissue. MRKH syndrome can have profound and lasting psychological impacts, making it essential for patients and their families to receive counseling both before and throughout treatment. A range of therapeutic options—both surgical and non-surgical—have been proposed for managing MRKH syndrome. Vaginal dilation remains the first-line treatment, as it offers high success rates with minimal risk of complications. Vaginoplasty is considered a second-line option for patients who do not respond to dilation therapy. Additionally, uterine transplantation and gestational surrogacy provide opportunities for women with MRKH syndrome to achieve biological motherhood. This review provides an updated overview of Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome, encompassing its etiological, clinical, diagnostic, psychological, therapeutic, and reproductive aspects. We also present a case involving a 19-year-old woman with MRKH syndrome who presented with primary amenorrhea, highlighting the crucial role and advantages of MRI in diagnosis, differential assessment, and treatment planning. Full article

Background: Testicular dysgenesis syndrome (TDS) is a complex disorder of the male reproductive system related to disfunction of the fetal testis. The clinical features of TDS may be evident at birth or infancy (cryptorchidism, hypospadias and/or reduced anogenital distance) or occur later in adulthood (testis cancer, infertility). Genetic background seems to be important for genetic predisposition, with new genes being associated with components of the syndrome in last years. Interestingly, the incidence of clinical manifestations of TDS has been increasing in many countries in recent decades, suggesting that genetic predisposition alone cannot explain this trend. Consequently, the hypothesis of multifactorial etiopathogenesis is becoming increasingly accepted nowadays, with environmental factors probably acting during early developmental stages in genetically predisposed individuals. Methods: In this narrative review, we aim to critically evaluate genetic and non-genetic factors involved in the pathogenesis of TDs. Results: Important associations with intrauterine growth disorders and maternal diseases (overweight/obesity and diabetes) as well as lifestyle factors (e.g., smoking and alcohol abuse) were found. In such context, endocrine disruptors probably play a major role. These substances are widely used in industry and can exert estrogenic and antiandrogenic effects, potentially interfering with the development of the fetal gonad. Conclusions: Considering their possible impact on male sexual health, more attention should be focused on maternal modifiable factors to confirm with prospective studies the mixed results of available evidence. Full article

Background/Objectives: Non-alcoholic fatty liver disease (NAFLD), also referred to as metabolic dysfunction-associated fatty liver disease (MAFLD), is the most common chronic liver disease, closely associated with obesity and Metabolic Syndrome (MetS). Perilipin-2 (PLIN2), the most abundant lipid droplet protein in the liver, is linked to lipid accumulation and inflammation, the hallmarks of NAFLD. The role of PLIN2 in NAFLD etiopathogenesis remains partially understood. This study aims to elucidate the relationship between serum PLIN2 levels and other disease-related parameters in NAFLD, investigate the role of PLIN2 in disease pathogenesis, and evaluate its utility as a biomarker in NAFLD diagnosis. Methods: The study included 46 patients diagnosed with NAFLD who presented internal medicine outpatient clinics and 44 healthy controls. Results: Serum PLIN2 level was found to be statistically significantly higher in the NAFLD patient group compared to the control group. In the NAFLD group, a statistically significant positive correlation was detected between PLIN2 and Body Mass Index (BMI), hip circumference, C-reactive protein (CRP), and platelet count. In ROC analysis, taking the cut-off value for serum PLIN2 level as 5.52 ng/mL predicted the diagnosis of NAFLD with 50% sensitivity and 97.7% specificity. Conclusions: PLIN2 determination demonstrated high specificity at the proposed cut-off value and may represent a promising complementary biomarker for NAFLD, particularly when interpreted alongside other clinical and laboratory parameters. Circulating PLIN2 appears to be influenced by metabolic and inflammatory parameters. Full article

Background/Objectives: Sepsis remains one of the leading causes of mortality, yet its etiopathogenesis is still not fully understood. This study aimed to investigate the effects of cetirizine and dexamethasone (alone and in combination) on serum levels of Maresin-1 (MaR-1), TNF-α, IFN-γ, IL-1, IL-2, IL-6, IL-8, and IL-10 in a rat model of sepsis induced by the cecal ligation and puncture (CLP) method. Methods: Male Sprague Dawley rats aged 8–10 weeks were used and randomly divided into 7 groups, each containing 7 rats: Group 1 (Control), Group 2 (Sham), Group 3 (Sepsis), Group 4 (Sepsis + Saline), Group 5 (Sepsis + Cetirizine), Group 6 (Sepsis + Dexamethasone), and Group 7 (Sepsis + Cetirizine + Dexamethasone). Sepsis was induced via CLP in all groups except Control and Sham. Results: In the sepsis groups (G3–G7), neutrophil and white blood cell counts increased while lymphocyte counts decreased (p < 0.05). In groups treated with cetirizine and/or dexamethasone (G5–G7), a significant decrease in neutrophils and an increase in lymphocytes were observed. MaR-1 levels significantly decreased (p < 0.05) in all sepsis-induced groups compared to controls, while interleukin levels significantly increased. Cetirizine and dexamethasone supplementation significantly increased MaR-1 levels and decreased interleukin levels (p < 0.05). The combined treatment was more effective. Conclusions: This study is the first to highlight the potential of MaR-1 as a critical biomarker in sepsis diagnosis and monitoring, and cetirizine and dexamethasone, especially in combination, may represent a promising therapeutic option in sepsis management. Full article

Idiopathic nephrotic syndrome (INS) is the most prevalent glomerular illness in children. Even while immunologic processes are well-established, oxidative stress is becoming more widely acknowledged as a significant factor in the etiopathogenesis of illness. Assessing its activity and treatment response may be made easier with the use of trustworthy, non-invasive indicators to track redox balance. We report on the oxidative stress levels of a 10.7-year-old boy with INS with five clinical time points in one year. The FRAS5 analyzer was used to calculate the oxidative stress index (OSI), plasma antioxidant capacity (PAT) and derivatives of reactive oxygen metabolites (d-ROMs) as biomarkers. A 4-tier oxidative state classification scheme based on d-ROM and PAT thresholds was used to interpret the values. The patient had low antioxidant defense, moderate oxidative and increased OSI at relapses, a positive transition to reduced oxidative burden and enhanced defense during remission. The order of events showed a dynamic redox response associated with glucocorticoid (GC) medication and disease activity. The potential value of d-ROM, PAT, and OSI as dynamic biomarkers for tracking disease activity, response to treatment and residual oxidative burden in pediatric INS is supported by this case. To confirm their function in more comprehensive clinical decision-making, more research is required. Full article

Endometrial carcinoma (EC) continues to represent a major cause of gynecologic cancer–related mortality among women worldwide. Its multifactorial etiopathogenesis and underlying molecular heterogeneity have been the focus of extensive investigation. While traditional histological classification provides essential diagnostic insight, it is limited in predicting prognosis and therapeutic response due to significant interobserver variability. Recent advances in molecular biology and cancer genomics have profoundly enhanced understanding of EC pathogenesis. The Cancer Genome Atlas (TCGA) project delineated four distinct molecular subtypes of EC, POLE ultra-mutated, microsatellite instability hypermutated (MSI-H), copy number low (CNL) and copy number high (CNH), each defined by unique genomic alterations, histopathologic features, and clinical behaviors. These molecular groups demonstrate significant prognostic and therapeutic implications, correlating with differential outcomes and treatment responses. This review summarizes current evidence on the genomic landscape of endometrial carcinoma and underscores the pivotal role of molecular classification in improving diagnostic accuracy, prognostic stratification, and personalized therapy. Ongoing research into molecular biomarkers holds promise for refining patient management and optimizing clinical outcomes. Full article

Background/Objectives: Atrial fibrillation (AF), characteristic of chaotic atrial electrical activity along with ineffective atrial systole, remains the most frequent sustained cardiac dysrhythmia, with an overall lifetime risk for AF being approximately 15% to 40% in the global population. AF is associated with substantially enhanced risks for multiple adverse clinical outcomes, including thromboembolic cerebral stroke, dementia, chronic kidney disease, myocardial infarction, cardiac failure, and even premature cardiac demise. Although remarkable advances have been achieved toward unravelling the complex hereditary etiopathogenesis underpinning AF, it has become increasingly clear that inherited determinants predisposing to AF in a vast majority of individuals are still uncertain. Methods: A Chinese pedigree with idiopathic AF and another group of 236 cases suffering idiopathic AF along with 312 unrelated healthy volunteers were prospectively recruited. Exome-wide sequencing and Sanger sequencing assays were implemented in research participants. The functional effects of the discovered variations in the SOX5 gene were explored through dual-luciferase reporter analysis. Results: Two novel SOX5 mutants, NM_006940.6: c.355C>T; p.(Gln119*) and NM_006940.6: c.640G>T; p.(Glu214*), were identified in the AF pedigree and one of the 236 unrelated patients affected with AF, respectively. These two heterozygous truncating SOX5 variations were absent from the 624 control chromosomes. Quantitative luciferase reporter assays unraveled that both Gln119*- and Glu214*-mutant SOX5 lost the ability to transactivate GJA1. Additionally, the two variations abolished the synergistic transactivation of SCN5A by SOX5 and SHOX2. Conclusions: The current findings indicate SOX5 as a novel gene contributing to AF, which adds more insight to the molecular pathogenesis of AF, and provides a potential target for personalized precision medicine. Full article

Redox unbalance, a molecular trait common to neurodegenerative conditions and para-physiological processes like aging, is a critical factor in disease development and in exacerbating progression. The mechanism by which redox imbalance perturbs cellular homeostasis is strongly linked to the activity and function of the ubiquitin–proteasome system (UPS). The UPS, along with autophagy, is the primary intracellular proteolytic system, regulating targeted proteolysis and removing damaged proteins. Consequently, the UPS serves also as the first line of defense for cellular recovery following exposure to redox stressors. Paradoxically, the composition and function of the UPS can also be negatively targeted by redox unbalance through a vicious cycle. The alterations in redox balance and UPS biological mechanisms are involved in the etiopathogenesis of chronic eye disorders. These disorders encompass a diverse repertoire of pathologies affecting the retinal layers (e.g., age-related macular degeneration, diabetic retinopathy) and the optic nerve (e.g., glaucoma). Nowadays, the comprehension of the interplay between proteostasis and oxidative redox status remains pivotal for identifying new therapeutic approaches. Encouragingly, a number of anti-oxidant compounds have been reported to modulate proteasome activity against redox insults in vitro and in vivo. Furthermore, these compounds provide cytoprotective roles in both in vitro and animal models of eye diseases. Therefore, this review highlights recent research on the interplay of the UPS with oxidative stress in physio-pathological conditions, focusing on the onset and progression of ocular diseases, thereby providing new insights into UPS-oxidative stress interaction. Full article

Background/Objectives: Hodgkin’s lymphoma (HL) is a cancer of the lymphatic system, the etiology of which remains partially unexplained, and environmental factors, including nutritional factors, may play an important role in its development and clinical course. The aim of this review was to examine the available literature on the impact of nutrition on the development and mortality of Hodgkin lymphoma. Methods: We conducted a literature review using databases, including publications from the last 10 years on nutrition and HL. Eventually, 3 publications were included in the review. Conclusions: Available data suggest that a diet rich in vegetables, fruits, fiber, and omega-3 fatty acids may have a protective effect, reducing the risk of developing Hodgkin’s lymphoma and improving prognosis and survival through anti-inflammatory and immune-supporting effects. On the other hand, excessive consumption of saturated fats, simple sugars and processed meat products can promote cancer transformation and worsen the course of the disease. Despite the promising results, further, well-designed prospective and interventional studies are needed to unequivocally determine the role of nutrition in the etiopathogenesis and treatment of HL. Full article

Background: Supernumerary teeth (ST) are developmental anomalies that may interfere with eruption, alignment, and occlusal balance. Their etiopathogenesis and management remain controversial. This multicentric study aimed to evaluate the epidemiological, morphological, and radiographic features of ST in a Romanian population and identify impact predictors. Methods: Between January 2020 and March 2025, 153 consecutive patients (91 males, 62 females; mean age 14.8 ± 6.2 years) with clinically and radiographically confirmed supernumerary teeth were evaluated across three Romanian academic centers: the University Dental Clinic, George Emil Palade University of Medicine, Târgu Mureș (n = 78 patients); the Department of Periodontology, Lucian Blaga University of Sibiu (n = 45 patients); and the Department of Dentistry, Dimitrie Cantemir University of Târgu Mureș (n = 30 patients). Results: A total of 185 ST were recorded, most frequently conical (48.6%) and mesiodens (56.2%). Complications were observed in 40.5% of patients. Multivariable analysis identified Angle Class III malocclusion (OR = 1.89; p = 0.039) and tuberculate morphology (OR = 2.93; p = 0.021) as the strongest independent predictors of impaction, alongside associations with younger age (<13 years) (OR = 3.12; p = 0.003) and male gender (OR = 1.78; p = 0.046). CBCT demonstrated high diagnostic concordance with OPG (κ = 0.89), but showed superior performance for complex cases, identifying 11 root resorptions and 9 vestibulo-palatal displacements that OPG missed. Multivariable analysis identified Angle Class III malocclusion (OR = 1.89; p = 0.039) and tuberculate morphology (OR = 2.93; p = 0.021) as the strongest independent predictors of impaction, alongside associations with younger age (<13 years) (OR = 3.12; p = 0.003) and male gender (OR = 1.78; p = 0.046). Conclusions: This multicentric study provides updated Romanian data and highlights novel risk factors and diagnostic selection guidelines that may support individualized treatment planning. Angle Class III malocclusion is a novel and critical independent predictor of supernumerary tooth impaction, alongside tuberculate morphology. This finding strengthens the rationale for utilizing CBCT specifically in Class III patients with ST to pre-emptively manage complex impactions and associated pathology. Full article

The points of contact between the vestibular system and the trigeminal nerve remain an active area of research. Anatomically, several connections have been clearly identified, and these may play a role in the development of various disorders. Understanding these connections also proves to be extremely valuable from a clinical perspective. It is increasingly evident that the etiopathogenesis of various vestibular disorders is multifactorial. Therefore, knowledge of the points of interaction between the two systems can assist clinicians in patient assessment and, most importantly, in selecting the most appropriate therapeutic approach. This study is presented as a narrative review. A literature search was conducted to identify studies investigating the correlation between the trigeminal system and the vestibular system, as well as their respective characteristics, to provide a comprehensive overview. Since this is a narrative rather than a systematic review, no specific inclusion or exclusion criteria were applied. So, the aim of this study is to analyze these connections through a comprehensive review of the literature, trying to present a multidisciplinary approach to the topic, one that can involve both the neurologist and the otologist, in order to achieve a more refined management of clinical cases. To better understand their anatomical relationships, we begin by examining the embryological development of both the vestibular system and the trigeminal nerve. Finally, we present current knowledge on the trigeminal influence in certain vestibular disorders—particularly vestibular migraine—and, conversely, the vestibular system’s potential impact on trigeminal-related conditions. Full article

Schizophrenia is a complex neuropsychiatric disorder characterized by a diverse range of symptoms, including positive, negative symptoms such as alogia, anhedonia, avolition, and affective flattening, cognitive symptoms, and emotional symptoms as a separate domain. Emerging evidence suggests that oxidative stress and neuroinflammation play crucial roles in the etiopathogenesis of schizophrenia. The aim of this review is the interplay between oxidative stress—defined as an imbalance between reactive oxygen species (ROS) production and antioxidant defenses—and neuroinflammatory processes within the central nervous system. Studies indicate that elevated levels of oxidative markers and pro-inflammatory cytokines are commonly observed in individuals with schizophrenia, pointing to a potential pathophysiological link. The dysregulation of redox homeostasis may exacerbate neuroinflammatory responses, contributing to neuronal damage and the subsequent manifestation of psychiatric symptoms. Furthermore, genetic and environmental factors may interact with these biological processes, influencing individual susceptibility to schizophrenia. Understanding the mechanisms by which oxidative stress and neuroinflammation contribute to the development and progression of schizophrenia could pave the way for novel therapeutic strategies aimed at mitigating these pathological processes and improving patient outcomes. Full article

Background: Mandibular lateral displacement is a common functional occlusal disorder that may occur independently or in conjunction with other types of malocclusion. Substantial evidence indicates that in growing patients, mandibular lateral displacement can have a significant negative impact on the development of both the morphology and function of the stomatognathic system. Early diagnosis and intervention are therefore crucial to preventing a range of developmental abnormalities, including skeletal and soft tissue asymmetries, temporomandibular joint dysfunction, and pathological tooth wear. Aim: The aim of this study is to analyze and systematize current scientific perspectives on the etiopathogenesis of mandibular lateral displacement, as well as approaches to its prevention and early treatment. Methods: A comprehensive review of the literature published between 1980 and 2025 was conducted. Sources were identified through searches in the PubMed, Google Scholar, Elsevier, Web of Science, and SUM Library databases. Results: Mandibular lateral displacement necessitates early diagnosis and timely initiation of orthodontic treatment. The majority of studies addressing the treatment of mandibular lateral displacement are limited to case reports. Conclusions: Further well-designed, longitudinal studies are needed to establish standardized diagnostic criteria and evidence-based treatment protocols for early management of mandibular lateral displacement in growing patients. Full article

The use of herbal medicines has gained popularity, both in science and among the public, as a natural alternative for the treatment of numerous diseases, including type 2 diabetes. Objective: The objective of this study was to evaluate peri-implant and long bone biomechanics in type 2 diabetic animals, treated or not with Bauhinia forficata. Methods: Thirty-two rats were allocated into four groups: normoglycemic (NG), normoglycemic + Bauhinia forficata (NGBf), type 2 diabetes (T2D), and T2D + Bauhinia forficata (T2DBf). Diabetes was induced using a cafeteria diet and streptozotocin (35 mg/kg). Bauhinia forficata tea (50 g/L) was administered to the NGBf and T2DBf groups. After 14 days, titanium implants were installed in the tibial metaphysis of all animals. Biomechanical analysis (removal torque), computerized microtomography, three-point bending test, confocal microscopy, and real-time PCR were performed. The results were tabulated, and a statistical test was conducted with a significance level of 5%. Results: Bauhinia forficata significantly improved the weight and blood glucose levels of the animals. In terms of biomechanics and the microarchitecture of long bones, T2D did not impair bone metabolism, and the use of the therapy did not cause significant changes in the parameters evaluated. However, T2D promoted significant impairment in the structural, biomechanical, and molecular characteristics of the peri-implant repair process, and the use of Bauhinia forficata increased the parameters evaluated in T2DBf. Conclusions: Type 2 diabetes mellitus significantly compromises peri-implant bone repair, with no influence on the metabolism of long bones, and Bauhinia forficata acts positively on both the etiopathogenesis of the disease and the tissue response to bone repair. Full article