Silvia Stratulat

Introduction. Dental fluorosis is an oral condition with aesthetic, psychosocial, and, in some contexts, functional implications that may extend beyond the clinical appearance of enamel. Interest in patient-reported outcome measures has increased because clinical severity alone does not explain how children and adolescents experience fluorosis in daily life. This manuscript aims to synthesize the evidence on oral health-related quality of life and to assess the relevance of a conditionspecific Oral Impacts on Daily Performance approach for dental fluorosis. Materials and methods. A narrative synthesis was prepared according to PRISMA-ScR guidance [REF]. The search framework was designed for PubMed/MEDLINE, Scopus, Web of Science, Embase, Cochrane Library, and the institutional repository of Nicolae Testemițanu State University of Medicine and Pharmacy. Core studies addressing dental fluorosis and oral health-related quality of life were extracted together with methodological papers on condition-specific OIDP, instrument adaptation, and Moldova-generated contextual literature. The methodological premises from the attached doctoral thesis on the Romanian adaptation of dental questionnaires were also integrated. Results. The evidence is heterogeneous. Mild dental fluorosis is often associated with no deterioration in oral health-related quality of life, while moderate to severe fluorosis is more consistently linked to worse quality-of-life outcomes. The most direct condition-specific OIDP evidence comes from a cross-sectional study in India showing significant correlations between fluorosis, CS-OIDP, and OHRQoL. A recent systematic review confirmed the mixed direction of results across 16 studies. Local Moldovan publications support the public health relevance of endemic fluoride exposure and the need for Romanian-language instruments adapted to this context. Conclusions. The current evidence supports the methodological relevance of a fluorosis-adapted CS-OIDP instrument. A future Romanian adaptation should combine rigorous translation procedures, cognitive testing, and psychometric validation, while retaining clinical measures of fluorosis severity for discriminative analysis.

Background/Objectives: The variability of the internal acoustic meatus (IAM) and its morphological peculiarities are of high clinical significance in otologic interventions and neurosurgery. Considering the complexity of the neurovascular structures housed by the IAM, including passage of the facial nerve, the aim of the study was to highlight the morphological peculiarities of the IAM and their clinical significance. Methods: The age peculiarities of the IAM course were studied on 18 serially, transversely sectioned human embryos and fetuses, as well as on 20 newborn and 20 adult formalin-fixed hemiheads. The morphometric parameters of the IAM (width, height, length, and angles between the anterior and posterior walls of the IAM and the longitudinal axis of the petrous ridge (LAPR) were evaluated on 82 dry temporal bones. Results: In embryos and early fetal stages of development, the course of the IAM formed an acute, posteromedially open angle with the longitudinal axis of the petrous part of the temporal bone (LAP); in newborns, it was a right angle; in adults, it was an acute, anteromedially open angle. Various shapes of the IAO, such as oval (51.2%), semioval (23.2%), quadrangular (13.4%), heart-like (3.7%), and triangular (8.5%), were highlighted. The mean width of the internal acoustic opening (IAO) was 7.7 ± 2.11 mm (right/left—8.2 ± 2.22 mm/7.2 ± 1.89 mm), with a statistically significant difference (p = 0.031). The mean height of the IAO was 5.3 ± 1.43 mm (right/left—5.6 ± 1.58 mm/5.0 ± 1.22 mm), p = 0.082. The mean length of the IAM was 10.1 ± 2.83 (right/left—10.5 ± 2.96 mm/9.7 ± 2.67 mm), p = 0.214. A partial septum was revealed in 3.6% of cases, while total septation of the IAM was observed in 2.4%. The mean angle between the anterior wall of the IAM and the longitudinal axis of the petrous ridge (AWIAM/LAPR) was 21.4 ± 13.67° (right/left—22.2 ± 14.62°/20.5 ± 12.78°), p = 0.564. The mean angle between the posterior wall of the IAM and the longitudinal axis of the petrous ridge (PWIAM/LAPR) was 82.4 ± 8.02° (right/left—84.3 ± 7.93°/80.5 ± 7.76°); p = 0.032. Conclusions: In the initial stages of an individual’s ontogenesis, the IAM forms an acute, posteromedially open angle with the LAP; in newborns—a right angle; in adults—an acute, anteromedially open angle. Both morphological characteristics and morphometric parameters of the IAO and IAM vary bilaterally. The oval, semioval, quadrangular, heart-like, and triangular shapes of the IAO were highlighted. Partial and total septation of the IAM were revealed. Only the TDAIO and PWIAM/LAPR angle were statistically significant, p < 0.05, while the bilateral correlation was negligible. The established morphological variants of the IAM could predispose to facial and vestibulocochlear nerve impairments.

Introduction: Thiosemicarbazones are heterocyclic compounds with diverse biological properties. They can exhibit anticancer, antioxidant, and pro-oxidative properties depending on their structure. The Advanced Glycation End-Products (AGE) pentosidine-like and vesperlysinelike compounds are actually involved in oxidative stress and diseases. This study aimed to determine the effect of copper-thiosemicarbazone coordination compounds for inhibiting AGEs with a comparison to a known pro-oxidative compound, Doxorubicin. Methods: Several copper coordination compounds of thiosemicarbazones were tested at two different concentrations (10.0 μmol/L and 1.0 μmol/L). The levels of pentosidine-like and vesperlysine- like AGEs were estimated and compared to those of controls and values after treatment with doxorubicin. Results: A high concentration of doxorubicin, CMD-8, MG-22, and TIA-160 remarkably enhanced the level of pentosidine-like AGE. Their values were up to four times higher than the control. For vesperlysine-like AGE, the effect was variable: the concentrations of CMD-8 and MG-22 remarkably increased the level, whereas CMC-34 remarkably decreased it. In the 1.0 μmol/L concentration, the modulating effect on AGE was less prominent; some compounds still affected the level. Discussion: The differing reactions of AGE subclasses imply distinct molecular mechanisms controlling pentosidine-like and vesperlysine-like AGE formation. The decrease levels of various AGE subclasses imply potential antiglycation/protective effects of certain compounds. Conclusion: Concentration- and structure-dependent effects of copper-thiosemicarbazones on AGE accumulation occur. There is a need in separate assessment of AGE subclasses to accomplish the evaluation of the metabolic role and therapeutic potential.

Cancer is characterized by profound metabolic alterations, including disturbances in acid-base balance and excessive lactate accumulation associated with aerobic glycolysis, this is being called the Warburg effect. These changes lead to acidification of the tumor microenvironment and promote epigenetic processes such as protein lactylation, influencing gene expression and tumor progression. The aim of this study was to elucidate the biochemical mechanisms underlying acid-base imbalances and the role of lactylation in cancer pathology. A narrative review of recent scientific literature focusing on tumor metabolism, pH regulation, and post-translational modifications has been conducted. The findings highlight the interconnection between lactate accumulation, tumor acidosis, and epigenetic regulation, these processes representing promising targets for the development of innovative therapeutic strategies in oncology.

Cancer utilizes metabolic reprogramming to resist oxidative stress, avoiding ferroptosis through the hyperactivation of nuclear factor erythroid 2-related factor 2 (NRF2), the cystine-glutamate transporter (SLC7A11), and glutathione peroxidase 4 (GPX4). The present study analyzes the role of the electrophilic product 4-hydroxynonenal (4-HNE) in neoplastic progression. Since the hyperactivation of this pathway, which is dependent on reduced glutathione (GSH), induces chemoresistance, its inhibition is vital. The research elucidates the mechanism by which doxorubicin induces the lipid peroxidation of mitochondrial cardiolipin, generating 4-HNE. At the same time, copper coordination compounds inhibit the antioxidant system through GSH depletion and catalyze Fenton reactions, forming toxic hydroxyl radicals. Thus, doxorubicin and copper compounds become potent inducers of ferroptosis. The dysregulation of redox homeostasis and the intensification of lipid peroxidation transform tumor vulnerability into an effective, lethal therapeutic mechanism.

One controversial issue in pituitary pathology is the simultaneous proliferation of PitNETs and endothelial cells. No previous studies have compared the MIB1 Labeling Index (MIB1 LI) of PitNETs and stromal endothelial compartments and its connection with VEGF protein and gene expression. Simultaneous PitNETs proliferation index assessment in tumor and endothelial cells is related to VEGF protein and gene expression, and by using the automated QuPath platform for digital image analysis (DIA), it can be determined whether this dual proliferation specifically characterizes certain PitNETs subtypes. A total of 109 PitNETs were immunostained for endothelial cells (CD34) and proliferation (MIB1). VEGF was assessed by using IHC and RNA scopes. QuPath_DIA measured hormone-dependent MIB1 nuclear expression in tumor and stromal endothelial cells. MIB1 LI correlated with VEGF_mRNA and protein expression. PRL-secreting and non-functioning PitNETs had a high MIB1 LI in stromal endothelial cells. MIB1-positive tumor cell (%MIB1 LI.T) and endothelial cell (%MIB1 LI.E) percentages were substantially correlated (p = 0.01). The profiles of VEGF and hormones significantly and heterogeneously impact the MIB1-LI of tumor and endothelial cells. Tumor–endothelial cell proliferative interaction is specific to PRL-secreting and non-functioning PitNETs. These findings suggest that digital analysis of MIB1 and VEGF expression may serve as a valuable tool for risk stratification in PitNETs.

Digestive tract cancer is a major public health problem in the Republic of Moldova, with increasing incidence and mortality rates in recent decades. Colorectal cancer is among the most common types of cancer, ranking third in cancer-related mortality statistics. An imbalance in the composition of the intestinal microbiota (dysbiosis) has been associated with the development of intestinal diseases, including colorectal cancer. A literature review was conducted covering the period from 2010 to 2025, using 35 articles sourced from ScienceDirect, PubMed Central, BioMed Central, Medscape, and GoogleScholar. The contemporary human diet contains many foods subjected to intense thermal processing such as frying, baking, and smoking, with a high content of advanced glycation end products (AGEs). These compounds lead to intestinal dysbiosis by reducing saccharolytic bacteria such as Ruminococcaceae and Alloprevotella, which produce short-chain fatty acids (SCFAs), and by increasing pathogenic bacteria like Desulfovibrio and Bacteroides. Firstly, dysbiosis, generated by AGEs, reduces SCFAs production, especially of butyrate, which has antiinflammatory, antitumor, and prokinetic effects. Secondly, pathogenic bacteria induce the formation of carcinogenic substances such as bacterial toxins and metabolic by-products of carbohydrates, proteins, cholesterol, and bile acids. Thirdly, pathogenic bacteria reduce the synthesis, metabolism, and assimilation of vitamins such as K2 (menaquinone), B7 (biotin), B12 (cobalamin), B9 (folic acid), B3 (niacin), B5 (pantothenic acid), B6 (pyridoxine), B2 (riboflavin), and B1 (thiamine). In conclusion, a diet low in AGEs, along with synbiotics, probiotics, prebiotics, and fecal microbiota transplantation, are promising methods for colorectal cancer prevention.

Ntroduction. In the context of increasingly intense athletic competition, athletes are motivated to enhance their performance through various methods, including the use of pharmacological substances that act on the adrenergic system. Among these, β2-adrenergic agonists are employed for their metabolic effects and their role in increasing endurance, whereas β-adrenergic antagonists are used in precision sports to reduce tremor and control anxiety. Both classes of substances present potential benefits as well as health risks, and are subject to strict regulations in high-performance sports. Material and methods. A theoretical study was conducted based on the analysis of specialized scientific literature, aiming to evaluate the impact of β2-adrenergic agonists and β-adrenergic antagonists on athletic performance. Additionally, the current regulations of the World Anti-Doping Agency (WADA) were analyzed. Results. β2-adrenergic agonists may contribute to the stimulation of muscle protein synthesis, enhancement of energy metabolism, and delay in the onset of fatigue. However, their use is associated with significant cardiovascular and metabolic side effects. β-adrenergic antagonists are effective in reducing tremor and sympathetic activation in precision sports but may decrease overall exercise capacity and induce bradycardia or chronic fatigue. Improper use of these substances can lead to severe sanctions in the context of athletic competitions. Conclusions. Although β2-adrenergic agonists and β-adrenergic antagonists may offer certain advantages depending on the specific nature of the sport, their use must be strictly medically regulated and comply with anti-doping standards. Careful evaluation of the risk-benefit ratio is essential for safeguarding athletes' health and preserving the integrity of competition.

Introduction. Micro-RNAs (miRNAs) are small RNA molecules that play an important role in the gene expression controlling in eukaryotic cells. Currently, circulating miRNAs are considered potential diagnostic biomarkers and therapeutic targets for cardiovascular diseases, including heart failure (HF). Materials and Methods. A literature review of the last 10 years was conducted, using 30 bibliographic sources, including those from the "Nicolae Testemițanu" USMF Scientific Medical Library and electronic libraries such as PubMed, Elsevier, Cambridge Journals Online, Hinari, Medline, and MedScape and the American Physiological Society Journal. Results. A number of studies have estimated the major role of miRNAs in the diagnosis and treatment of HF. Increased expression of miR-21, miR-182, miR-122, has been observed in the plasma of patients with heart failure. The prognostic value of miRNA-182 was found to be superior to that of natriuretic peptide and high-sensitivity C-reactive protein in HF. Increased expression of miR-30d acts as a "protective factor" against hypertrophy and tumor necrosis factor-αmediated apoptosis. At 33 days post-ischemia/reperfusion injury, hearts treated with antimiR-21 showed reduced cardiac fibrosis and hypertrophy, along with improved regional and global cardiac function. The treatment with CDR132L led to a significant reduction in cardiac remodeling, as evidenced by a decrease in the left ventricular end-systolic volume and left atrial volume on magnetic resonance imaging (MRI), along with attenuation of myocardial interstitial fibrosis and cardiomyocyte size on histological examination. Conclusions. miRNAs play a key role in regulating molecular processes involved in heart failure development and progression, such as cardiac hypertrophy, fibrosis, apoptosis, and inflammation. The dysregulation of specific miRNAs contributes to disease progression and deterioration of cardiac function. Identifying specific miRNAs as biomarkers and therapeutic targets provides promising opportunities for the development of more effective treatments and early diagnostic methods in heart failure

Serum biomarkers represent a key pillar in the non-invasive assessment of liver fibrosis. Although biopsy remains the gold standard, the APRI and FIB-4 scores have emerged as simple and accessible alternatives, particularly in healthcare systems with limited resources. The aim of the study was to evaluate the utility of the non-invasive diagnostic scores APRI and FIB-4 in identifying liver fibrosis, in comparison with histological findings from liver biopsy. The cross-sectional observational study included all patients with chronic liver disease who were hospitalized at the Republican Clinical Hospital (Chișinău) between 2019 and 2024 and underwent liver biopsy. APRI and FIB-4 scores were calculated based on clinical and biochemical data. Liver fibrosis was confirmed histologically. Results are expressed as mean ± standard error of the mean (M±SEM). The study sample included 22 patients, of whom 40.9% were male and 59.1% female, with a mean age of 44.5±2.7 years. The APRI score identified a high risk of liver fibrosis in 40.9% of patients (n=9), while the FIB-4 score indicated a high risk in 9.1% (n=2) and an intermediate risk in 22.7% (n=5). Liver fibrosis was histologically confirmed in 45.5% of patients (n=10). Discrepancies between non-invasive scores and biopsy findings may be attributed to their variable sensitivity and the characteristics of the study cohort. APRI and FIB-4 are useful tools for the initial evaluation of liver fibrosis. While APRI showed better alignment in excluding fibrosis, FIB-4 demonstrated higher accuracy in identifying advanced fibrosis and estimating intermediate risk.