BACKGROUND:The development of targeted anticancer agents capable of selectively eliminating breast cancer cells while sparing normal tissues remains a critical therapeutic challenge. MCB-04, a novel dihydropyrimidinone (DHPM)-tethered piperazine derivative synthesized via a TiO₂ nanoparticle-mediated catalytic strategy, demonstrates promising anticancer potential. OBJECTIVES:This study aimed to synthesize DHPM-tethered piperazine derivatives using a TiO₂-catalyzed approach and to comprehensively evaluate the cytotoxic efficacy of the lead compound MCB-04 against human breast cancer cells, with particular emphasis on elucidating its underlying molecular mechanisms of cell death. METHODS:A library of DHPM-tethered piperazine derivatives was synthesized and characterized, and MCB-04 was identified as the lead compound. Cytotoxicity was assessed using the MTT assay in MDA-MB-231, MCF-7, BT-474, and SK-BR-3 breast cancer cell lines, as well as normal MCF-10A cells. Apoptosis and autophagy were analyzed by live/dead assays, Annexin V/PI staining, immunocytochemistry, and Western blotting. Mitochondrial dysfunction and oxidative stress were evaluated by measuring mitochondrial membrane potential (Δψm) and intracellular ROS levels using flow cytometry. The involvement of paraptosis and c-Met-mediated signaling pathways was further investigated. RESULTS:MCB-04 exhibited potent and selective cytotoxicity toward breast cancer cells, with the highest sensitivity observed in MDA-MB-231 cells (IC50 = 20 µM), while exerting minimal toxicity in normal MCF-10A cells. MCB-04 treatment significantly increased intracellular ROS levels and disrupted Δψm, indicating mitochondrial dysfunction. Mechanistically, MCB-04 induced apoptosis through activation of cleaved PARP and cleaved caspase-3, an increased Bax/Bcl-2 ratio, and upregulation of p53 and phosphorylated p53. Concurrently, autophagy was evidenced by LC3-II accumulation and increased Atg5 and Beclin-1 expression. Markers of ER stress-mediated paraptosis, including ATF4 and CHOP, were also elevated with concomintant decline in Alix. Furthermore, MCB-04 markedly suppressed phosphorylated c-Met, EMT-related VEGF, MMP-9 expression and downstream PI3K/Akt/mTOR/MEK signaling pathways. CONCLUSION:MCB-04 exerts robust anti-breast cancer activity by triggering multiple programmed cell death pathways include apoptosis, autophagy, and paraptosis primarily through ROS-mediated mitochondrial dysfunction and inhibition of c-Met-dependent oncogenic signaling. These findings position MCB-04 as a promising multi-targeted therapeutic candidate, warranting further in vivo validation and preclinical development for breast cancer treatment.

INTRODUCTION:The brain's complexity arises from intricate neural circuitry and dynamic molecular interactions. While genomics and proteomics have expanded understanding of brain pathology, lipidomics- particularly through metabolite and membrane lipid profiling-has emerged as a critical tool for elucidating phenotype-specific molecular mechanisms, especially those underlying neurodevelopmental and neurodegenerative disorders. Given the brain's high lipid content and the role of bioactive lipids in neural function, a deeper understanding of age-specific lipidomic landscapes is essential. Methods: A comprehensive literature review was conducted using scientific databases such as PubMed, Scopus, and Web of Science. Key search terms included "lipidomics," "brain development," "neurodegeneration," "mass spectrometry," "neonatal brain," and "adult brain." Studies that applied advanced mass spectrometry techniques for brain lipid profiling, including LC-MS and GC-MS, were prioritized. The review focused on the identification, function, and clinical relevance of lipid species across age groups and neurological conditions. Results: Distinct lipidomic profiles were observed between neonatal and adult brains. Neonatal brains were enriched in DHA-containing phospholipids, which are critical for synaptogenesis and neuronal growth. In adult brains, lipids such as sphingolipids and cholesterol showed higher abundance and functional diversity, contributing to membrane integrity, signal transduction, and neuroprotection. Alterations in lipid metabolism were linked to various neurological disorders, notably multiple sclerosis, Alzheimer's disease, and Parkinson's disease. The review also identified challenges in lipidomics data integration, standardization, and its application to clinical diagnostics. Discussion: The findings highlight the critical importance of lipidomics in understanding brain development and neurodegeneration. Age-specific lipid signatures not only provide insights into the molecular basis of neurological disorders but also offer promising avenues for early diagnosis and therapeutic targeting. Despite advances in mass spectrometry and data analysis, challenges remain in integrating lipidomic data with other omics layers, necessitating further methodological and computational developments. Ultimately, lipidomics represents a transformative approach to decoding brain biology across the lifespan. Conclusion: This review elucidates the pivotal role of lipidomics in revealing age-specific molecular signatures in the brain, with clear distinctions between neonatal and adult lipid profiles. In neonatal brains, DHA-enriched phospholipids are fundamental for neurodevelopmental processes such as synaptogenesis and myelination, whereas in adult brains lipid networks are more complex, supporting neuronal maintenance, signaling, and neuroprotection. Dysregulation of these lipid pathways is closely associated with the pathophysiology of neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease, and Parkinson's disease. Advanced mass spectrometry technologies have facilitated high-resolution lipid profiling, enabling the identification of potential biomarkers and therapeutic targets. The broader implications of these findings are that lipidomics, when integrated with multi-omics approaches, can significantly enhance understanding of brain function and disease across the lifespan, ultimately informing the development of personalized diagnostic tools and age-specific therapeutic strategies for neurological disorders.

BACKGROUND:Ovarian reserve reflects the functional capacity of a woman's ovaries, encompassing factors such as follicle quantity, egg quality, and fertilization potential. Assessment of ovarian reserve is essential in reproductive medicine, particularly for fertility evaluation and assisted reproductive technologies (ART). While traditional biochemical markers such as anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH) are commonly used, instrumental diagnostic methods like ultrasound and magnetic resonance imaging (MRI) provide valuable morphological and functional insights. This systematic review without a comprehensive meta-analysis evaluates the role of ultrasound and MRI in assessing ovarian reserve and their potential applications in clinical and research settings. METHODS:A comprehensive literature search was conducted across multiple databases to identify relevant studies evaluating ovarian reserve using ultrasound and MRI. Studies were screened based on predefined inclusion criteria, focusing on imaging parameters such as ovarian volume, follicular count, stromal characteristics, and vascularization. The effectiveness of these imaging techniques was analyzed in comparison to established biochemical markers. Due to heterogeneity in the included studies, a systematic review was performed without a formal meta-analysis. RESULTS:Ultrasound, particularly transvaginal ultrasound (TVUS), remains the gold standard for ovarian reserve assessment, allowing real-time visualization of antral follicle count (AFC), ovarian volume, and follicular morphology. Doppler ultrasound provides additional insights into ovarian blood flow, which correlates with follicular development and ovarian function. MRI offers high-resolution, three-dimensional imaging, enabling detailed assessment of ovarian structure, follicular density, and stromal composition. While MRI provides superior soft-tissue contrast, its role in routine ovarian reserve assessment is limited due to cost and accessibility. The findings indicate that although both modalities are valuable for ovarian reserve evaluation, there is no consensus on standardized imaging parameters for defining ovarian functional viability. The available literature also presents inconsistencies in the correlation between imaging findings and ovarian function. CONCLUSION:Ultrasound and MRI are essential tools for assessing ovarian reserve, providing complementary morphological and functional data. However, the lack of standardized imaging parameters limits their ability to definitively determine ovarian functional viability. Further research is needed to establish validated diagnostic criteria and integrate imaging techniques with biochemical markers to enhance the accuracy of ovarian reserve assessment in clinical practice and reproductive research.

Breast cancer is a profound cause of mortality among women globally. Similar to BH3 mimetics, targeting the antiapoptotic Bcl-xL:Beclin1 protein complex is crucial to inducing apoptosis and autophagy, thereby suppressing tumor progression in breast cancer cells. This study aims to synthesize and evaluate a series of imidazopyridine-tethered pyrazoline drug prejudice-scaffold derivatives (5a-5l) as Beclin-1 mimetics that induce apoptosis and autophagy and mainly for their potential anticancer activity, focusing on the most potent compound 5c. The primary goal is to assess its ability of compound 5c to inhibit Bcl-xL:Beclin-1 interaction, thereby inducing a protective autophagic response subsequently to assess apoptosis to suppress breast cancer cell proliferation. Molecular docking studies were conducted to evaluate the binding affinity of compound 5c with Bcl-xL, and the interactions were visualized through a three-dimensional interaction map, highlighting key stabilizing interactions. Cytotoxic effects of compound 5c on MCF-7 breast cancer cells were assessed using alamarblue assay. To investigate the antiproliferative potential, colony formation, and wound healing assays were performed at varying concentrations. Apoptotic induction was analyzed through Western blotting for key proteins (BAX, Bcl-xL, Bcl-2), caspase-3/7 activation, and AnnexinV/PI assay using flow cytometry. Additionally, autophagy was examined by monitoring LC3B-I to LC3B-II conversion, Beclin-1 upregulation, and lysosomal activity using LysoTrackerRed staining. The involvement of compound 5c in autophagic flux was further confirmed by quantifying LC3-II accumulation in the presence of an autophagy inhibitor chloroquine (CQ), and then the effect of 5c-induced cell viability and apoptosis were evaluated and caspase-3/7 activity, respectively, during autophagy inhibition condition in MCF-7 cell line. A strong binding interaction of compound 5c with the hydrophobic groove of Bcl-xL demonstrated its potential as an effective Bcl-xL inhibitor. Compound 5c significantly reduced MCF-7 cell viability in a dose-dependent manner (IC50: 9.7 μM). The inhibitory effect of compound 5c on cancer cell proliferation and migration was observed. Treatment with compound 5c induced dose-dependent apoptosis in MCF-7 cells, as confirmed by Annexin V/PI using flow cytometric analysis after 72 h of exposure. A significant decrease in viable cells accompanied by an increase in apoptotic cell populations was observed with increasing concentrations of 5c. Upregulated BAX expression and downregulation in Bcl-xL and Bcl-2 expression levels indicated apoptosis induction. Caspase-3/7 activation further confirmed apoptotic cell death. Autophagy assessment revealed enhanced LC3B-II accumulation, Beclin-1 upregulation, and reduced p62 levels, suggesting modulation of autophagy. CQ treatment further increased LC3-II levels, indicating compound 5c-mediated autophagic flux induction and a significant reduction in cell viability and increased caspase 3/7 activity, confirming modultion of autophagy-dependent apoptosis by 5c. Similar to BH3 mimetic, compound 5c emerges as a promising small-molecule inhibitor targeting the Bcl-xL:Beclin-1 complex, which effectively induces apoptosis by modulating protective autophagy in breast cancer cells. Its dual mechanism of action highlights its potential as a novel therapeutic candidate for breast cancer treatment.

Trefoil Factor 3 (TFF3) is an oncogenic protein implicated in breast cancer progression through regulation of PI3K-AKT, MAPK, STAT3, and NF-kappa B signaling pathways. Targeting TFF3 therefore represents a promising therapeutic strategy. In this study, chromene-3-carbonitrile derivatives were synthesized using nano-TiO2 as an efficient catalyst and evaluated for their anticancer potential against TFF3 in MCF-7 breast cancer cells through combined in vitro and in silico approaches. Thermodynamic feasibility of the synthetic process was assessed using free energy calculations. Cytotoxicity of the synthesized compounds was determined in MCF-7 cells, while molecular docking studies were performed to investigate binding interactions with TFF3. Protein expression analysis was performed using western blotting to confirm TFF3 inhibition. Several derivatives demonstrated significant cytotoxic activity, with lead compounds F8, F10, F12, and F13 exhibiting IC50 values of 0.751, 1.70, 0.68, and 0.52 & micro;M, respectively. Docking studies revealed strong binding affinity and favorable interactions with TFF3 and energy profiling supported the thermodynamic viability of synthetic route. Western blot results further confirmed downregulation of TFF3 expression. Overall, these findings identify chromene-3-carbonitrile derivatives as potent TFF3-targeting agents with potential therapeutic relevance for breast cancer.

BACKGROUND In recent years, many developed countries have implemented prevention programs aimed at introducing the younger generation to regular physical activity and creating a health-promoting sports environment. Of particular importance is prevention of repeated sports bone injuries, which are the main cause of early disability and reduced work capacity in young athletes. An important factor in preventing fractures during physical activity is the early identification of an underlying predisposition to bone injuries, which is associated with connective tissue dysplasia (CTD). At present, the only way to diagnose a predisposition to bone injuries is molecular genetic testing, which identifies mutations in genes encoding CTD components. However, this technique is complex, expensive, and time-consuming, so it is not available for practicing sports physicians and cannot be recommended for rapid screening. AIM To identify clinically significant dysplastic signs of predisposition to bone injuries and to assess their diagnostic value in verifying individuals prone to bone damage. METHODS This cross-sectional study was performed at Sechenov University in accordance with STROBE guidelines. A total of 538 young adults (18-35 years) involved in sports were examined. Participants were divided into a main group with repeated bone injuries and a control group without such history. Screening for more than 80 dysplastic signs was performed through questionnaires, diagnostic tests, anthropometric and phenotypic assessments, and instrumental studies (esophagogastroduodenoscopy, ultrasound, X-ray examination/computed tomography). Statistical analyses were conducted using StatTech v. 4.8.11 software. Significance was set at P < 0.05. RESULTS The results indicated that the dysplastic phenotype in young athletes is characterized primarily by external dysplastic stigmata, with osteoarticular manifestations being the most prevalent. Repeated sports-related bone injuries were observed in 6.7% of young adults involved in mass sports (95% confidence interval [CI]: 4.59%-8.81%). The bone fractures/cracks were more frequently associated with sports involving high mechanical load on bones (wrestling, weightlifting). CTD syndrome plays a significant role in bone re-injury genesis. The dysplastic severity (total CTD score) determines the bone re-injury risk (area under the curve = 0.759; 95%CI: 0.665-0.852, P < 0.001). The level of CTD severity, which indicates a predisposition to bone injuries, was defined as the dysplastic re-injury threshold (DRIT) for bone re-injury incidence. The value of this indicator was 44.2 CTD scores. An approach for identifying predisposition to bone injury based on the total CTD score was established. The dysplastic phenotype of individuals predisposed to recurrent bone injury is characterized predominantly by an asthenic body type, dolichostenomelia, arachnodactyly, chest deformities (pectus carinatum or pectus excavatum), a narrow facial skeleton, and a high-arched (gothic) palate. The most common complaints in this group were paresthesia and muscle spasms/cramps. It was demonstrated that none of the dysplastic features associated with recurrent bone injury is sufficient on its own to identify individuals predisposed to bone injury. However, the presence of each of these characteristic dysplastic features is clinically significant and is associated with a substantially increased risk of bone injury. CONCLUSION The high incidence of recurrent bone injuries among young adults participating in recreational sports underscores the importance of its preventive strategies. Screening for connective tissue abnormalities during the initial medical evaluation, with consideration of the characteristic dysplastic features identified in this study, may help identify athletes at increased risk who could benefit from closer monitoring and individualized injury prevention strategies. Determining the DRIT for recurrent bone injury enables early risk stratification and the implementation of targeted preventive measures, supporting personalized strategies to preserve musculoskeletal health in young athletes. The dysplastic phenotype associated with susceptibility to bone injury is characterized by a distinct constellation of dysplastic features that, when considered collectively, may provide the basis for the development of a rapid screening method to identify individuals at increased risk of bone injury.

Background Intracranial giant dermoid cysts (GDCs) are rare congenital lesions that may reach large sizes and produce neurological symptoms. Surgical management is challenging due to their proximity to critical neurovascular structures, and outcomes largely depend on the extent of resection achieved. Case summary We report two adult cases of intracranial GDCs with ≥10-year follow-up: one treated with subtotal resection requiring multiple re-operations, and another managed with gross-total resection followed by late focal recurrence. Additionally, a targeted literature review was conducted using PubMed/MEDLINE, Scopus, and the Cochrane Library for English-language articles published from January 2000 to January 2026. The search identified 315 records; after removal of 82 duplicates, 233 records were screened. Thirty-seven full-text articles were assessed for eligibility, and 17 studies met inclusion criteria for qualitative synthesis. Extracted variables included imaging characteristics, surgical approach, extent of resection, complications, recurrence, and follow-up duration. Results MRI remains the cornerstone for diagnosis. Typical findings include T1 hyperintensity suppressed on fat-saturated sequences, variable T2 signal, and minimal or absent contrast enhancement. Intact dermoids usually lack diffusion restriction, distinguishing them from epidermoids. Ruptured lesions show T1-bright fat droplets, fat–fluid levels, and sulcal hyperintensity on contrast-enhanced FLAIR, consistent with chemical meningitis. Recurrence was associated with indistinct arachnoid planes, multicompartmental extension, and capsular adherence to major vessels. Innovation We propose the Reyes–Encarnacion imaging classification, an MRI-based system that incorporates lesion size (>5 cm), arachnoid plane clarity, multicompartmental involvement, and rupture status. It categorizes GDCs into Types A–E, with rupture as a modifier (R), linking imaging features to surgical strategy, risk profile, and follow-up intensity. Conclusions This imaging-guided framework may standardize reporting and enhance surgical decision-making in GDCs. The Reyes–Encarnacion classification is hypothesis-generating and requires prospective validation, including interobserver reliability and outcome correlation.

Background & aims Urological malignancies are major contributors to the global cancer burden. This study aims to provide a comprehensive, sex-stratified assessment of the 2022 baseline and project trajectories to 2050 for prostate, bladder, and kidney cancers to inform long-term surgical oncology and healthcare planning. Methods Baseline estimates for 185 countries were retrieved from GLOBOCAN 2022, with longitudinal trends from GBD 2021. We employed a dual-modeling framework: demographic forecasting for absolute case volumes and Bayesian Age-Period-Cohort (BAPC) models for age-standardized risk trends (ASIR/ASMR), including 95% uncertainty intervals (UI). Results In 2022, urological cancers accounted for 2.52 million new cases and 773,968 deaths globally. While prostate cancer dominated male burden, bladder and kidney cancers posed a notable clinical demand in both sexes. Higher HDI correlated with higher ASIR but lower mortality-to-incidence (M:I) ratios. A critical sex-specific divergence was observed: BAPC models predicted risk declines in females, but stable or modestly rising risks in males through 2050, likely driven by escalating metabolic factors. Paradoxically, the absolute global burden is projected to increase by 92.5%, reaching 4.85 million cases and 1.74 million deaths annually by 2050. The sharpest relative increases (>100%) are expected in low-to-medium HDI regions, where mortality growth is projected to outpace incidence. Conclusion The urological cancer landscape faces a dual challenge of population aging and stagnating male-specific risks. Our findings describe an urgent need to expand urological surgical capacity and infrastructure, particularly in transitioning economies, to accommodate the inevitable surge in operative demand despite favorable risk trends in specific populations.

INTRODUCTION:Signal Transducer and Activator of Transcription 3 (STAT3) is a key mediator in Breast Cancer (BC) progression, contributing to tumor proliferation, metastasis, survival, and resistance to chemotherapy. Phosphorylation of STAT3 at tyrosine 705 promotes its dimerization and nuclear translocation, where it activates oncogenic transcriptional programs. Due to its central role in BC pathogenesis, STAT3 has emerged as a promising molecular target for therapeutic intervention. To synthesize, characterize, and evaluate the anticancer efficacy of synthetic and natural compounds with a focus on their ability to inhibit STAT3 phosphorylation, suppress breast cancer cell proliferation, and induce apoptosis and autophagy. METHODS:A comprehensive literature review was conducted using databases such as PubMed, Scopus, Relemed, and ResearchGate. Relevant studies were identified that examined the synthesis, molecular mechanisms, and therapeutic potential of STAT3 inhibitors. Synthetic derivatives and phytochemicals were considered for their inhibitory effects on STAT3 activation and associated cellular outcomes in breast cancers. RESULTS:Several synthetic and natural compounds demonstrated significant inhibitory effects on STAT3 phosphorylation, leading to reduced breast cancer cell proliferation, migration, and survival. These agents effectively induced apoptosis and, in some cases, autophagy, highlighting their multifaceted anti-tumor mechanisms and elucidating the potential of these compounds as lead candidates for further preclinical and clinical development. CONCLUSION:Targeting STAT3 can be a significant therapeutic strategy, as both synthetic and natural compounds capable of inhibiting STAT3 signaling have been shown in preclinical studies. These findings provide valuable insights for cancer biologists, molecular researchers, and clinicians to explore STAT3 inhibitors as potential breast cancer therapeutics.

The focus of this review is on the molecular mechanisms leading to otolconia dysfunction. The nervous system creates a real picture of changes in the body's position in space through the vestibular apparatus, which consists of the otolithic organs and the semicircular canals located in the inner ear. It determines the ability to navigate in space and coordinate parts of the body and the whole body. Degeneration of the otolithic receptors of the utricle disrupts spatial orientation and leads to the condition known as benign paroxysmal positional vertigo. It is the most common pathology of the peripheral vestibular system and is characterized by sudden, transient vertigo when the position of the head in space changes. To date, it is generally accepted that the cause of benign paroxysmal positional vertigo is a violation of the integrity of the otolithic membrane of the macula of the utricle and saccule, resulting in the intrusion of the otoconia into one or more semicircular canals. The result is abnormal stimulation of the cupula either by free floating otoconia in the endolymph of the semicircular canal (canalolithiasis) or by otoconia attached to the cupula (cupulolithiasis). Literature on benign paroxysmal positional vertigo published on Pubmed and Google Scholar was reviewed using key words such as “benign paroxysmal positional vertigo “, ‘‘inner ear protein,’’ ‘‘biomarkers of BPPV,’’ and several specific protein searches such as ‘‘otolin-1’’ and “PMCA” based on findings from the initial searches. For an interdisciplinary understanding of the functioning of the peripheral vestibular apparatus in normal and pathological conditions, we have systematized data on its functional anatomy and pathophysiological conditions leading to benign paroxysmal positional vertigo. The analysis of the latest data from basic research on the etiology of otolithic receptor degeneration is presented in our research. As a "growth point" for further studies of the structure of otolithic receptors, we presented the development of methods for the diagnosis of benign paroxysmal positional vertigo based on the detection of structure-forming proteins of the otoconia in the patient's blood as its molecular biomarkers.

A large number of complications associated with incorrect visualization of the facial artery or ignorance of the anatomy of the major facial vessel make this problem quite relevant. An in-depth understanding of anatomical variations, projections and topography, taking into account the depth of the facial artery, can help reduce the risk of adverse outcomes during cosmetic procedures. In addition, it assists plastic and maxillofacial surgeons in managing facial trauma and performing surgical procedures, including advanced endoscopic facelift techniques and endoscopic blepharoplasty, where the risk of vascular injury is higher. In cases of vascular injury, anatomical knowledge allows the selection of an optimal hemostatic approach. The aim of this review is to systematize current data on anatomical variations, topography, and external landmarks of the facial artery, providing a classification and visual representation of different patterns. This structured information will undoubtedly benefit clinicians in various fields.

While 2-Indolyl-1,3,4-oxadiazole derivatives are recognized for their antibacterial properties, their potential as anticancer agents remains underexplored. This study investigates the anti-breast cancer properties of a novel 2-Indolyl-1,3,4-oxadiazole compound, 5l, focusing on its ability to induce apoptosis, paraptosis, and autophagy, and targeting poly (ADP-ribose) polymerase (PARP1), a critical enzyme in DNA repair. A series of 1,3,4-oxadiazole derivatives (compounds 5a-5m) were synthesized using an optimized multi-step process, enhancing reaction efficiency and yield. In silico molecular docking was used to determine binding efficacy of these derivatives. Lead compound, 5l, underwent cytotoxicity assays against MDA-MB-231, MCF-7, BT-474, and SK-BR-3 breast cancer cell lines, as well as the non-cancerous MCF-10A cell line. Molecular docking assessed the interaction of 5l with the PARP1 active site. Frontier molecular orbital (FMO) and molecular electrostatic potential (MESP) analyses were conducted to map electron distribution and identify reactive regions within compound 5l. The effects of 5l on cellular processes such as apoptosis, autophagy, and endoplasmic reticulum (ER) integrity were evaluated using live and dead assays, Annexin V staining, ER-tracker dye staining, and acridine orange assays. Western blotting analyzed apoptosis, paraptosis, and autophagy-related genomic instability. The optimized synthesis yielded high-purity 1,3,4-oxadiazole derivatives. Compound 5l displayed significant anticancer activity, with IC50 values of 63.7 μM, 29.1 μM, 50.3 μM, and 39.8 μM for MDA-MB-231, MCF-7, BT-474, and SK-BR-3 cell lines respectively, demonstrating its cytotoxic efficacy. Molecular docking revealed that 5l binds to PARP1 active site with a binding energy of -11.7 kcal/mol, indicating a strong interaction supporting its role as a PARP1 inhibitor. Annexin V assays, ER-tracker dye staining, and Acridine orange assays were used to assess apoptosis, ER integrity, and autophagy. 5l induced upregulation of cleaved PARP and downregulation of Alix-loaded proteins, alongside increased LC3-II expression, indicating autophagy-mediated genomic instability. Compound 5l exhibits potent anti-breast cancer activity through paraptosis, apoptosis, and autophagy-mediated genomic instability and by PARP1 inhibition with typically a low IC50 values, highlighting its potential as a therapeutic agent.

Aim - to study age–related features to identify different structural variants of the common carotid artery bifurcation using ultrasound imaging. Materials and methods. A survey include of 1,061 volunteers (57.0±10.7 years old). The results were grouped according to age and gender, and statistically processed. Results. 2,122 vascular complexes were studied (1,396 in women and 726 in men). There are 5 main types formed. Types A and B prevailed (up to 42% type A). Type B is up to 35% among men, 27% among women. Type B is up to 19% among women, and in men in 15% of cases. Other options were 4-7%. When dividing the participants based on gender and age, 4 groups of observation participants were formed. Type A among women in all groups was 41-43%, for men the frequency of this variant was 31-40%. For men, the highest detection of type B was noted in the first age group – 48%. Type B was determined in groups 1-3 2-4% more often among women, and in group 4 more often among men – 31%. The highest values for type D were noted in the group of men - 12% in the 4th age group, in other cases, types D and D in most cases are 4-7%. Conclusions. As a result, the predominance of type A among women was noted. Types A and B were more often identified among all participants. Type B was often found in young men. There has been an increase in the diagnosis of type B with age. Rare variants accounted for 4-7% of cases. The study of the variable anatomy of the main arteries of the neck makes it possible to develop personalized directions in the treatment of vascular diseases and improve minimally invasive surgical interventions.

To identify factors affecting the mental and physical health of first-year medical students during the period of rapid SARS-COV-2 spread in the COVID-19 pandemic to develop effective strategies for managing student well-being and education quality during global pandemics. 656 first-year students of Sechenov University aged 17 to 23 years (17.91 ± 1.01 years) were included in an online anonymous survey. The study consisted of two assessment phases: in traditional training in September-December 2021 and in distance learning in January-March 2022. The State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory, the Cantril Self-Anchoring Scale, and an original questionnaire were used for evaluation. During the rapid COVID-19 spread in COVID-19 pandemic, most first-year medical students had a high level of reactive anxiety, accompanied by depressive disorders and vegetative-somatic manifestations that significantly reduced their adaptive potential, life quality and academic performance. All first-year students regardless of age were shown to be sensitive to stressful situation. The females demonstrated more pronounced psycho-vegetative changes compared to the males. Students of medical, pediatrics and medico-preventive faculties reacted more strongly to the current situation than students of dental and pharmaceutical faculties. The identified changes in the psycho-vegetative student status were associated, first of all, with the difficult sanitary-epidemiological SARS-COV-2 situation and related financial problems. Students considered the transition to distance learning to be the most important support measures. Temporary transition to distance learning led to the significant decrease in the anxiety level, correction of depressive and vegetative manifestations, and significant increase in the life quality that was of great importance for the education quality. Significant student support measures during COVID-19 pandemic were also financial, psychological and informational assistance. The obtained results made it possible to develop the effective strategies for managing student health and education quality during global pandemics.

Introduction: Approximately 70 % of patients with breast cancer (BC) have estrogen receptor (ER)-positive tumors. Endocrine therapy is the principal treatment for these patients. Tamoxifen (TAM), a selective ER modulator, is commonly administered to premenopausal patients with ER-positive BC. However, resistance to TAM poses a major clinical hurdle as TAM-resistant BC cells often show increased proliferation and motility as well as undergo epithelial-mesenchymal transition (EMT). Objective: Pyrimidine-based small molecules were reported as both nuclear factor kappa B (NF-κB) and Wnt/β-Catenin pathway regulators. This report discovered oxazine (TRX-01) linked pyrimidine as an inhibitor of NF-kB and triazole (TTP-5) linked pyrimidine as an inhibitor of Wnt/β-Catenin signaling in TAM-resistant MCF-7 breast cancer cells (MCF-7R). Methods: Colony formation, wound healing, and Transwell assays were conducted to assess cell migration and invasion. MTT assay was used to evaluate cytotoxic effects. Western blotting was used to determine the signaling mechanisms for NF-κB and EMT phenotypes. Xenograft models were utilized to examine the in vivo effectiveness of TRX-01. Results: TRX-01 reversed TAM resistance in MCF-7R cells, whereas TTP-5 reduced the motility of MCF-7R cells. Additionally, TRX-01 inhibited the activation of the NF-κB signaling pathway in MCF-7R cells, whereas TTP-5 inhibited the EMT-like phenotype of MCF-7R cells by impairing the activation of Wnt/β-catenin signaling. The differences in the functions of the two pyrimidine structures are attributed to their additional structures bearing both TRX-01 and TTP-05. Conclusion: Pyrimidine-based TRX-01 and TTP-5 lead structures are promising agents for inhibiting the progression of TAM-resistant breast cancer cells. These results support the need for additional comprehensive in vivo and clinical studies to confirm the efficacy and safety of these compounds.

Background and objective The complexities of spinal surgery, particularly the intricacies of cervical pathology, demand precision and expertise in surgical interventions. Cervical laminoplasty is a procedure that requires meticulous execution and a profound understanding of delicate anatomical structures. Recognizing the limitations of traditional training methods, this study highlights the transformative impact of integrating 3D modeling and printing technologies into medical education. These technologies provide an immersive, interactive, and highly detailed training platform, enabling aspiring surgeons to visualize, dissect, and practice procedures in a risk-free environment. Beyond education, 3D models enhance patient-doctor communication, enable precise preoperative planning, facilitate custom implant design, and support a personalized approach to spinal surgery. Collectively, these advancements hold the promise of reducing surgical errors and improving outcomes. Materials and methods Thirty-eight participants, including neurosurgeons, residents, and medical doctors, were enrolled in this study. High-resolution CT scans, obtained with informed consent to ensure confidentiality and ethical compliance, were used to create the 3D models. These models, printed with polylactic acid (PLA) filament and refined through post-processing, achieved high anatomical accuracy and quality. The training program combined lectures, live demonstrations, and hands-on sessions with 3D models. Participants' experiences and perceptions were evaluated through a survey, focusing on the models' utility and realism in advancing surgical skills. Results The participants overwhelmingly praised the 3D models for their utility in helping to understand cervical laminoplasty concepts and enhancing their learning compared to traditional methods. The models were particularly valued for their accurate representation of anatomical structures and improved visualization of surgical steps. Notably, 81.6% of participants found the models extremely beneficial in planning surgical approaches. The survey results unanimously highlighted the transformative potential of 3D models in medical education. Participants strongly recommended their integration into training programs and preoperative planning processes, emphasizing their ability to elevate the learning experience and improve surgical preparedness. Conclusions Our findings show that 3D modeling significantly enhances training in cervical laminoplasty by providing superior learning tools and improving anatomical visualization compared to conventional methods. The unanimous endorsement from participants underscores the adaptability and precision of 3D models in medical education and preoperative planning. As an indispensable resource in modern medical training, these models represent a pivotal advancement in preparing surgeons for the complexities of spinal surgery.

Background: Rh4 (a compound derived from ginsenoside) has excellent anti-tumor property. It has been documented that an abnormally elevated level of Notch3 expression is linked to poor prognosis of gastric cancer (GC). Currently, the function of Rh4 in GC malignant progression is still unclear, and the manner in which Notch3 regulates GC progression remains undefined. Methods: The level of Notch3 in GC cells was determined utilizing qRT-PCR and western blot. The relationship between Notch3 level and patient overall survival was forecasted by Kaplan-Meier Plotter database. The impacts of Notch3 and Rh4 on the biological characteristics of GC cells were examined through CCK-8, clone formation, scratch healing, and transwell assay. Using western blot, PI3K/Akt pathway protein levels were measured. Finally, a mouse subcutaneous transplantation tumor model was utilized to explore the influence of Rh4 treatment in vivo. Results: The level of Notch3 was notably elevated in GC. The patient’s overall survival exhibiting high Notch3 levels was considerably lower than those with low expression. Silencing of Notch3 reduced GC cell viability and inhibited malignant progression. Rh4 exhibited a dose-dependent decrease in GC cell viability. In addition, Rh4 significantly suppressed Notch3 levels in GC cells, with over-expression of Notch3 attenuating the inhibitory influence of Rh4 on GC malignancy. Notch3 over-expression activated the PI3K/Akt pathway, while Rh4 effectively blocked this pathway by targeting Notch3, but PI3K agonists reversed this effect. Rh4 treatment reduced Notch3 expression and hindered tumor growth in vivo by inhibiting the PI3K/Akt pathway. Conclusion: Notch3 expression was found to be heightened in GC, but Rh4 effectively suppressed PI3K/Akt pathway by targeting Notch3, and subsequently inhibiting cell proliferation, migration, and invasion.

To review the functional morphology of the corpus callosum. The corpus callosum is the largest connection between the cerebral hemispheres. The left hemisphere is responsible for abstract logical thinking in right-handers, while the right hemisphere is responsible for figurative and artistic information processing (this view is too schematic and not quite true, although it has exerted a considerable influence on the media and common sense knowledge). This article presents the evolution of views on the functional role of the corpus callosum and its formation at various stages of ontogenesis. It also discusses anomalies and disorders of interhemispheric interactions that are usually mediated by this commissure. The age and anatomical features of the corpus callosum require special attention. The article emphasizes the necessity of multidirectional studies of the corpus callosum. Information on the clinical and anatomical characteristics of the corpus callosum will be valuable not only for morphologists but also for neurologists, neurosurgeons, psychiatrists, speech pathologists, etc. This will provide a broader perspective on many topical issues in neurology and psychiatry.

Personalizing deep brain stimulation (DBS) for Parkinson’s disease remains challenged by trial-and-error programming and feature-engineered models that fail to capture critical 3D spatial-field interactions, as traditional volume of tissue activated (VTA) models focus exclusively on the spatial extent of activated tissue and lose substantial information such as continuous electric field distributions, gradients, and directional properties. To overcome these limitations, we developed DeepPoint-DBS, a point cloud framework integrating submillimeter imaging, biophysical modeling, and AI for precision efficacy prediction. In a retrospective cohort study, we analyzed 561 individuals with Parkinson’s disease implanted with directional DBS leads (Medtronic 3389 and Pins L301), who underwent preoperative 3T MRI (T1/T2-weighted) and postoperative CT scans, with motor outcomes assessed via MDS-UPDRS-III in OFF-medication/ON-stimulation states across approximately 640 parameter combinations (amplitude: 1.0–4.0 V, 130 Hz fixed frequency). Patient-specific point clouds (~ 227,500 points/subject) integrated MRI-derived anatomy of deep-brain nuclei including STN and GPi, high-resolution electric-field vectors from finite-element simulations, and electrode geometry with active contact locations, processed via a hierarchical PointNet + + architecture to predict MDS-UPDRS-III improvements. DeepPoint-DBS achieved 62.5% accuracy in identifying optimal stimulation parameters, representing a 37.5% relative improvement over conventional feature-based approaches such as SVR and LR, with predicted MDS-UPDRS-III improvements demonstrating correlation with clinical outcomes. By preserving 3D field-tissue interactions at high resolution, this clinically deployable framework shifts DBS programming from postoperative trial-and-error to precision planning, potentially halving treatment optimization time and facilitating personalized selection of effective parameter combinations for Parkinson’s disease management.

INTRODUCTION:Breast cancer is the leading cause of cancer-related death in Mexico, with high mortality associated with spinal bone metastasis. We propose to standardize a murine model of bone metastasis to study and understand the tumor microenvironment. MATERIALS AND METHODS:An experimental, prospective, longitudinal study was conducted using 18 CD1/Nu/Nu 30g nude mice. Two cell lines, MCF-7 and 4T1, were inoculated, clinical follow-up was performed, and biopsy samples were obtained for histopathological evaluation. RESULTS:Histopathological evaluation of models inoculated with the MCF-7 cell line showed no tumor development, while inoculation with the 4T1 cell line resulted in tumor development, as evidenced by PET-CT and histopathology, using 5,000 and 1,000 cells, respectively. CONCLUSIONS:The use of this model is proposed for studying the clinical, molecular, and prognostic aspects of breast cancer progression by inoculating 1,000 cells of the 4T1 cell line.