The aim of our study was to compare brain tissue net water uptake (NWU), cerebral oxygenation, and microcirculation changes in perilesional penumbra foci (PPF) in moderate isolated traumatic brain injury (moiTBI) patients. Materials and Methods: 77 moiTBI patients (women 35; men 42, age 37 years [34;39]) with unilateral frontal/frontotemporal lesions (Marshall II-III) were included in this retrospective, non-randomized, single-center study. Perfusion parameters were measured in PPF zones and determined using multiphase perfusion computed tomography (PCT) in the first 2 days after trauma and admission. NWU in hypoattenuated perilesional zones was calculated using non-contrast CT. Cerebral oxygenation (SctO2) was simultaneously measured using near-infrared spectroscopy in the frontal lobes with PCT. Data are shown as a median [interquartile range]. Statistical analysis was performed using nonparametric statistics. P < 0.05 was considered statistically significant. Results: In PPF, SctO2 was 64.03

Natural antioxidants are essential for protecting the body against oxidative stress and exhibit a wide range of biological activities. In this context, forty extracts derived from ten submerged cultivated mushroom species were analyzed for their mycochemical composition, antioxidant capacity, and cytotoxic effects against MCF7 breast cancer cells. Qualitative and quantitative screening revealed that, among the detected classes of bioactive compounds, the extracts were predominantly enriched in flavonoids, terpenoids, and phenolic constituents. Considerable variation was observed in the levels of total phenolics, flavonoids, and ascorbic acid among different species and solvent extracts. The highest total phenolic contents were detected in ethanol and ethyl acetate extracts of G. frondosa (110.0 +/- 6.4, 227.6 +/- 14.2, and 160.5 +/- 5.3 mg GAE/g), while the water extract of F. velutipes also exhibited elevated phenolic levels (119.2 +/- 6.5 mg GAE/g). Flavonoid concentrations ranged from 102.5 +/- 10.5 to 359.9 +/- 2.5 mg QE/g in biomass and culture liquid extracts obtained with organic solvents. Ascorbic acid content was generally highest in ethyl acetate culture liquid extracts, suggesting solvent-dependent enrichment of antioxidant metabolites. Free radical scavenging activity increased in a concentration-dependent manner, reaching inhibition values more than 90% at 20 mg/mL in all tested mushrooms. Cytotoxicity assays demonstrated that extract type, solvent, and incubation time strongly influenced the inhibition of MCF7 cell viability. Ethyl acetate extracts from H. erinaceus, P. ostreatus, T. versicolor, and T. pubescens exhibited the strongest cytotoxic effects, reducing cell viability by up to 70% at higher concentrations. The results demonstrate that mushroom extracts, particularly ethyl acetate extracts, possess significant antioxidant and cytotoxic activities. These findings highlight their potential as promising natural sources of medicinal bioactive compounds for antioxidant and anticancer applications.

Herein, we present the synthesis of three types of graphene oxide quantum dots (GOQDs) having different dopants, namely, nitrogen and boron. Doped GOQDs were successfully synthesized via a one-step top-down hydrothermal treatment of graphene oxide in the presence of H2O2 and appropriate dopant precursors. The nanoparticles were characterized using TEM, XPS, UV-vis, and photoluminescence spectroscopy. The applied strategy provides a reproducible route to anisotropic nanoparticles with heights in the range of 1.0-1.5 nm and lateral sizes in the range of 7-10 nm, with a well-defined graphenic structure of the core and defined compositional and optical characteristics, highlighting the advantages of top-down approaches over bottom-up methodologies for systematic structure-property investigations. XPS analysis demonstrated nitrogen incorporation into the graphenic lattice of all studied GOQDs, primarily in pyrrolic and graphitic forms, whereas the introduction of boron through boric acid or 3-aminophenylboronic acid predominantly affected edge functionalities. Biological evaluation revealed a pronounced dependence of antibacterial activity on GOQD composition. Among the three materials, nitrogen-doped GOQDs exhibited broad-spectrum bactericidal activity against the ESKAPE-(E) panel, with a particularly low MBC of 8 μg/mL against Staphylococcus aureus. Boron- and nitrogen-co-doped GOQDs exhibited pronounced bacteriostatic activity against S. aureus within the concentration range of 100-4 μg/mL. Cytotoxicity assays using HaCaT keratinocytes demonstrated that N-GOQDs combine effective antibacterial performance with excellent cytocompatibility, achieving bacterial eradication at concentrations that remain entirely nontoxic to human skin cells. The results provide clear structure-activity insights and position N-GOQDs as a promising platform for developing next-generation antibacterial nanomaterials targeting multidrug-resistant ESKAPE pathogens.

Sulfonylated 5-piperazine-substituted 1,3-oxazole-4-carbonitriles were synthesized and evaluated for in vitro anticancer activity. Cytotoxicity was assessed in hepatocellular (HepG2, Huh7), breast (MCF-7, MDA-MB-231), cervical (HeLa), melanoma (M21), and neuroblastoma (Kelly, SH-SY5Y) cell lines, with HEK293 cells used as a non-malignant control. Compounds 7a, 7b, and 8aa emerged as lead structures. Notably, compound 7b showed the highest activity in Kelly neuroblastoma cells (IC50 = 1.3 µM) while exhibiting low cytotoxicity toward HEK293 cells (IC50 > 10 µM), indicating an improved selectivity profile relative to doxorubicin. In silico molecular docking suggested favorable interactions of the lead compounds with several cancer-associated proteins, with the highest predicted affinity observed for Aurora A kinase, along with additional predicted interactions with cyclin-dependent kinases. Predicted ADMET properties of compounds 7a, 7b, and 8aa compared favorably with doxorubicin, although the lead compounds were not readily biodegradable under OECD 301D conditions. Overall, these findings identify oxazole-4-carbonitriles as promising anticancer candidates with a putative kinase-directed mechanism of action.

Introduction: Reperfusion therapies, such as thrombolysis with tissue plasminogen activator and endovascular thrombectomy, are the cornerstone of acute stroke treatment, aiming to restore blood flow to the ischemic brain. However, even after successful recanalization of large vessels, many patients experience incomplete recovery due to persistent microvascular dysfunction. This can manifest as “no-reflow” phenomenon, endothelial dysfunction, inflammation, and reperfusion injury, all worsening tissue damage and outcomes. Drag-reducing polymers (DRP), high-molecular-weight macromolecules given intravenously at nanomolar levels, improve microvascular perfusion by lowering resistance and optimizing hemodynamics. This study assessed high-molecular-weight DRP time-dependent efficacy in restoring cerebral microcirculation, reducing infarct volume, and mitigating blood-brain barrier (BBB) damage in a rat transient middle cerebral artery occlusion (tMCAO) model. Methods: Adult Wistar rats underwent 3.5-hour monofilament tMCAO with reperfusion. Subjects were randomized to intravenous DRP (5 ppm) or saline at 1 or 3 hours post-occlusion. At baseline, immediately, and 3.5 hours after tMCAO, laser speckle contrast imaging (LSCI) quantified cortical cerebral blood flow (CBF). At 24 hours, neurobehavioral deficits were assessed (modified Bederson scale, limb asymmetry, rotarod). Evans Blue (2%, 4 mL/kg i.v.) quantified BBB permeability via spectrofluorometry (μg/g tissue). Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining with edema correction using ImageJ. Differences were analyzed by two-way ANOVA with Tukey's post-hoc; data as mean ± SEM, p<0.05. Results: tMCAO reduced CBF by 62.4±5.1% (p<0.001), causing BBB leakage (8.7±0.9 μg/g), infarct (215.8±18.3 cu mm), and deficits (score 12.5±1.1). DRP improved CBF (1h: 58.3±4.2% baseline; 3h: 49.1±3.8%; vehicle: 37.6±3.2%; both p<0.01). Infarct decreased (1h: 112.3±12.5 cu mm, p<0.01; 3h: 148.7±14.1 cu mm, p<0.05). BBB permeability reduced (1h: 4.1±0.5 μg/g; 3h: 5.8±0.6 μg/g; both p<0.01). Scores improved (1h: 5.2±0.8; 3h: 7.1±0.9; both p<0.05). Efficacy was time-dependent (1h>3h, p<0.05). Conclusion: DRP, administered up to 3 hours post-tMCAO, enhances cerebral microcirculation and collateral flow, limits infarct and BBB damage, and improves outcomes, positioning it as a promising adjunct therapy for thrombolysis and thrombectomy.

Gastrin releasing peptide receptor (GRPR) is overexpressed in prostate cancer (PC). Currently, radiopharmaceuticals (RP) for visualization of GPRP based on bombesin antagonists are developed. The aim of the present work was to conduct a phase I clinical trial of the GRPR antagonist [99mTc]Tc-RM26 and to study the possibility of its use for PC SPECT imaging. Thirteen patients diagnosed with PC were included in the study. Patients received [99mTc]Tc-RM26 intravenous bolus at a dose of 640±165 MBq (40 μg/injection). Six patients underwent whole-body planar imaging and SPECT/CT at 2, 4, 6, and 24 h after injection. Seven patients had SPECT/CT alone performed 2 h after RFP injection. The study showed that a single intravenous injection of [99mTc]Tc-RM26 is safe and well tolerated. Critical organs for RFP are the gallbladder, small intestine, upper colon and kidney. The dose burden per patient associated with the administration of [99mTc]Tc-RM26 RFP is 3–6 mSv per study. The studied RP allows to visualize primary prostate malignant tumors, as well as its metastases to lymph nodes and bones. It is reasonable to conduct further clinical studies of [99mTc]Tc-RM26 to evaluate the sensitivity and specificity of SPECT/CT with this RP for diagnostics and staging of prostate cancer.

Background/Objectives: The gastrin-releasing peptide receptor (GRPR) shows high-density expression in prostate cancer (PCa), especially in the early stages of the disease. The introduction of a safe radiotracer for assessing GRPR-expression in PCa may serve as an alternative or complementary tracer to PSMA-directed probes for patients with insufficient PSMA expression. In the present study, the tolerability and safety, biodistribution, and dosimetry of the new GRPR-targeting radiopeptide [99mTc]Tc-DB8 were investigated for the first time in male PCa patients. A mass escalation study was performed, aiming to improve tumor-to-background contrast and, thereby, to enhance diagnostic accuracy. Methods: Sixteen male patients were enrolled in a single-center diagnostic open-label exploratory Phase I clinical trial. Patients were administered a single intravenous injection of 40, 80, or 120 µg of [99mTc]Tc-DB8 peptide (n = 5–6) and underwent whole-body planar imaging (anterior and posterior) 2, 4, 6, and 24 h post-injection (pi) and SPECT-CT acquisition 2, 4, and 6 h pi. Results: Administration of [99mTc]Tc-DB8 was well tolerated at all tested peptide masses. The effective dose did not differ significantly between the injected peptide mass and was 0.005 ± 0.003 mSv/MBq. High activity uptake was observed in the pancreas and kidneys, which 3-fold decreased with an increasing injected peptide mass from 40 to 120 µg. The activity uptake in primary tumors did not differ significantly between cohorts injected with different peptide masses [SUVmax 1.65–9.96]. The tumor-to-muscle ratios increased with time and were the highest for the cohort injected with 120 µg of peptide, 7.2 ± 3.1 (4.64-11-25) at 4 h pi. Conclusions: Single intravenous administration of [99mTc]Tc-DB8, for visualization of GRPR expression in PCa using SPECT imaging was well tolerated in a peptide mass range of 40–120 µg. An injected peptide mass of 80–120 µg/patient and SPECT acquisition 2–4 h pi were found to be optimal for further clinical studies due to the significantly lower activity accumulation in the pancreas and kidneys.

Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein, which is overexpressed in several types of malignancies. Designed ankyrin repeat protein (DARPin) Ec1 is a 19 kDa engineered scaffold protein that binds with high affinity to EpCAM. Radiolabelled Ec1 might be used as a companion diagnostic for the selection of patients for personalized therapy. This study aimed to investigate the influence of different radiometal-chelator complexes on the biodistribution and imaging contrast of 68Ga-labelled Ec1. To investigate this, two macrocyclic chelators, 1,4,7-triazacyclononane-N,N,N-triacetic acid (NOTA) and 1-(1,3-carboxypropyl)-1,4,7-triazacyclononane-4,7-diacetic acid (NODAGA) were conjugated to the C-terminus of the Ec1. The previously developed DARPin Ec1 conjugated to 1,4,7,10-tetraazacylododecane-1,4,7,10-tetraacetic acid (DOTA) was used as a comparator. All Ec1 variants were successfully labelled with 68Ga. The use of NOTA and NODAGA provided twice higher radiochemical yield and improved label stability compared to DOTA. All labelled Ec1 variants bound to the EpCAM-expressing cells with nanomolar affinity and preserved targeting specificity in vitro and in vivo. Biodistribution studies in mice bearing EpCAM-expressing SKOV-3 xenografts showed that [68Ga]Ga-Ec1-NOTA had lower uptake in most normal organs while maintaining tumor uptake. Among all variants, [68Ga]Ga-Ec1-NOTA showed the lowest liver uptake, with no significant differences in tumor uptake. Additionally, [68Ga]Ga-Ec1-NOTA provided the highest tumor-to-blood ratio compared to [68Ga]Ga-Ec1-DOTA and [68Ga]Ga-Ec1-NODAGA. [68Ga]Ga-Ec1-NOTA is the preferred radioconjugate for PET imaging of EpCAM expression.

Neuroblastoma, a leading cause of pediatric cancer mortality, requires efficient and selective therapeutics. We synthesized and characterized a series of sulfonated 5-piperazine-containing 1,3-oxazole-4-carbonitrile derivatives via sulfonylation protocols and evaluated their in vitro cytotoxicity against human hepatocellular carcinoma (HepG2, Huh7), breast (MCF7, MDA-MB-231), cervical (HeLa), melanoma (M21), and two neuroblastoma (Kelly, SHSY5Y) cell lines, alongside non-malignant HEK293 cells. Three compounds (7a, 7b, and 8aa) demonstrated efficient and selective cytotoxicity toward MYCN-amplified (Kelly) and MYCN-non-amplified (SHSY5Y) neuroblastoma cells, with 7b being the most active (IC₅₀ = 1.9 µM in Kelly cells) and showing minimal toxicity in HEK293 (IC₅₀ > 10 µM). In Kelly cells, 7b matched doxorubicin while showing lower off-target toxicity and low-micromolar activity in solid tumors. The hit compounds were shown to be not readily biodegradable under OECD 301D test. In silico docking revealed high-affinity binding to the ATP-binding site of Aurora A kinase in the Aurora A/N-MYC complex (ΔG = –10.8 to –10.9 kcal/mol). Compound 7b exhibited broad cytotoxicity across all tested cancers (IC₅₀ = 1.5–4.0 µM). ADMET profiling of 7a, 7b, and 8aa indicated favorable pharmacokinetic and toxicity parameters compared with doxorubicin. These findings identify sulfonylated oxazole-4-carbonitriles as neuroblastoma therapeutics with potential use against proliferating malignancies.

Purpose: The uncoupling of cerebral oxygenation is interconnected with brain hydration dynamics and is essential for understanding the characteristics of intracerebral hemorrhage pathomorphosis. The aim was to study the brain hydration and cerebral oxygen saturation status changes in perilesional penumbra foci (PPF) in moderate isolated traumatic brain injury (moiTBI) patients. Materials and Methods: Seventy-seven moiTBI patients (women 35 and men 42, median age 37 years) with unilateral lesions (Marshall Score II-III) were included in this study. Net water uptake was measured in PPF using non-contrast computed tomography (NCCT) 2 days after admission. NWU in hypoattenuated zones of PPF was calculated using NCCT. Cerebral oxygen saturation (SctO2) was measured in the frontal lobes. Data are shown as a median [interquartile range]. Statistical analysis was performed using nonparametric statistics. Results: In PPF, SctO2 was 64.03

Введение. Определение состояния регионарных лимфатических узлов является обязательным этапом догоспитальной диагностики у больных раком молочной железы для определения локальной и системной тактики лечения. Несмотря на развитие современных диагностических методик, определение HER2 статуса регионарных лимфатических узлов до сих пор имеет свои недостатки. Цель. Изучение возможности использования радиофармпрепарата [99mTc]Tc-ADAPT6 для дифференцировки статуса HER2 в метастатических аксиллярных лимфатических узлах у больных раком молочной железы. Материал и методы. В анализ были включены 20 больных раком молочной железы (T1-4N1-3M0-1) до начала системного лечения. Больные были разделены на 2 группы в зависимости от статуса рецептора HER2: 12 человек с положительной экспрессией и 8 человек с отрицательной. Всем больным вводился радиофармпрепарат (РФП) [99mTc] Tc-ADAPT6 в дозировке 500 мкг, ОФЭКТ/КТ органов грудной клетки и верхнего этажа брюшной полости проводилось через 2 ч. после введения. Оценка накопления соединений выполнялась путем измерения максимального стандартного захвата (SUVmax) метастатических аксиллярных лимфатических узлов (мАЛУ), проекции контрлатеральной аксиллярной области, проекций референсных органов (печень, широчайшая мышца спины (ШМС) и селезенка), далее определяли соотношения мАЛУ/фон, мАЛУ/печень, мАЛУ/ШМС, мАЛУ/селезенка, наиболее информативный параметр выявляли с использованием ROC- анализа. Результаты. Все мАЛУ были визуализированы с использованием [99mTc] Tc-ADAPT6 через 2 ч. после инъекции. SUVmax мАЛУ, а также соотношения мАЛУ/фон, мАлу/печень, мАЛУ/ШМС и мАЛУ/селезенка были выше у пациентов с высокой экспрессией HER2 (р < 0,005, Mann – Whitney test). Наиболее информативным параметром для дифференцировки статуса HER2 в мАЛУ, по данным ROC–анализа являлся SUVmax мАЛУ при пороговом значении более 4,22 усл. ед. (чувствительность — 91,67 % и специфичность — 100 %) (р = 0,0003, Mann – Whitney test). Выводы. Использование РФП [99mTc]Tc-ADAPT6 эффективно для детекции HER2 статуса в метастатических лимфатических узлах у больных раком молочной железы. Наиболее информативным параметром для дифференцировки статуса HER2 в метастатических лимфатических узлах является SUVmax мАЛУ (чувствительность — 91,67 %; специфичность — 100 %) при пороговом значении — > 4,22 усл.ед.