PubMed Central

Background/Aim: Osteosarcoma (OS) treatment consists of chemotherapy with methotrexate, adriamycin (doxorubicin) and platinol (MAP) combined with intercalated surgery, resulting in a 5-year survival rate of 50–60%. We recently demonstrated that local delivery of doxorubicin via a microparticulate hydroxyapatite-based biomaterial (DASH) could efficiently impede tumor growth in subcutaneous OS; however, its effect in an orthotopic intraosseous OS remains unknown, particularly in conjunction with systemic MAP treatment. In this study, we performed two separate mouse model studies with the aim of (1) evaluating the effect of DASH in an orthotopic osteosarcoma model and (2) evaluating the efficacy and tolerability of DASH in conjunction with systemically administered MAP in a subcutaneous osteosarcoma model. Methods: In the first study, 56 mice were inoculated with human OS cells (i.e., h143B cells) in the proximal tibia. After 10 days, the mice were divided into seven treatment groups, of which group G2 (systemic DOX) was compared with groups G5–G7, which were treated with increasing doses of DOX delivered via DASH. The tumor-impeding response was evaluated via micro-CT (day 14), PET-CT (day 21) and tumor measurements (post-mortem). In the second study, 45 mice were inoculated subcutaneously with 143B cells and, 10 days later, groups G2–G5 were treated locally with increasing DASH doses, followed by two cycles of systemic MAP for all groups. On day 31, the animals underwent PET-CT examination followed by euthanasia and tumor measurements. Results: In both experiments, DASH treatment resulted in significantly lower tumor activity, tumor volume and weight. Micro-CT examination in the orthotopic model demonstrated that DASH treatment protected the bone from osteolysis. The subcutaneous study revealed that the mice were able to tolerate DASH, even in conjunction with systemically administered MAP. Conclusions: Intratumoral administration of DASH impeded OS growth in both animal models and protected bone against tumor-induced osteolysis. Furthermore, DASH was well-tolerated when administered in conjunction with systemic MAP therapy, indicating its potential therapeutic neo-adjuvant value in poor responders.

Various Spirulina species and their major pigment, Cyano-phycocyanin (C-PC), have been shown to exhibit antioxidant, anti-inflammatory, and anticancer properties, and are used in various skincare products. Spirulina platensis is rich in nutrients, proteins, and antioxidants, with therapeutic potential for skin protection and regeneration. Aqueous Spirulina extracts have gained increasing attention in recent years due to their biocompatibility; however, comparative assessment of aqueous extract and C-PC responses across non-malignant and malignant skin cells remains limited. This study aimed to evaluate the effects of S. platensis aqueous extract and C-PC on the cellular metabolic activity and wound healing of human skin cell lines—melanoma cells, keratinocytes, and fibroblasts—using a 24 h PrestoBlue assay and time-resolved scratch assays. The results demonstrated a concentration- and cell-type-dependent response to both preparations: at selected concentrations, S. platensis aqueous extract and C-PC reduced melanoma cellular metabolic activity while increasing it in keratinocytes and fibroblasts. Notably, both S. platensis aqueous extract and C-PC significantly accelerated wound closure at selected concentrations in keratinocytes and fibroblasts but not in melanoma cell cultures. Additionally, the S. platensis extract exhibited strong antioxidant activity, which correlated with its phenolic and flavonoid content. In conclusion, S. platensis aqueous extract and C-PC exhibit concentration- and cell-type-dependent effects on skin cell metabolic activity and scratch closure, supporting further investigation of their potential for skin-repair applications.

Background/Objectives: The complex nature of endodontic/periodontal lesions complicates treatment prognosis, making long-term tooth survival challenging to predict. Identifying key prognostic factors can facilitate evidence-based clinical decision-making. This systematic review aims to evaluate the available evidence on factors associated with treatment outcomes in endodontic/periodontal lesions and to identify potential prognostic indicators. Methods: PubMed/MEDLINE, Embase, Web of Science and Cochrane Library were searched from 1 June to 1 July 2026 with no restrictions. Observational studies investigating associations between baseline prognostic factors and treatment outcomes in adults with endodontic/periodontal lesions were eligible for inclusion. Study selection and data extraction were performed independently by two reviewers. Risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool, and certainty of evidence was evaluated using GRADE. Due to substantial methodological heterogeneity, the findings were synthesized narratively rather than through meta-analysis. Results: Four retrospective studies comprising 501 teeth were included. Risk of bias was predominantly moderate to high, and certainty of evidence was low. No single factor demonstrated directionally consistent independent association across the available adjusted analyses. Conclusions: Despite limited evidence, an overall pattern suggests that endodontic/periodontal lesion prognosis may be most frequently associated with the extent of periodontal tissue destruction and the amount of remaining periodontal support. Prospective studies using standardized endodontic/periodontal lesion definitions, outcomes and appropriately adjusted multivariable prognostic models are needed.

Background and Objectives: The Canadian Occupational Performance Measure (COPM) is a widely used client-centered outcome measure designed to evaluate individuals’ self-perceived occupational performance and satisfaction with performance. Although an official Lithuanian version is available, its psychometric properties have not previously been evaluated in individuals undergoing poststroke rehabilitation. This study aimed to examine the test–retest reliability, concurrent validity, and responsiveness of the Lithuanian version of the COPM. Materials and Methods: Thirty-one individuals with subacute stroke participated in this prospective validation study. Test–retest reliability was assessed over a three-day interval using the intraclass correlation coefficient (ICC). Concurrent validity was examined by correlating COPM Performance and Satisfaction scores with the Functional Independence Measure (FIM). Responsiveness was evaluated by comparing baseline and discharge COPM scores following inpatient rehabilitation. Additional exploratory analyses assessed whether demographic or clinical characteristics were associated with COPM scores. Results: The Lithuanian version of the COPM demonstrated high test–retest reliability, with ICC values of 0.974 (95% CI: 0.947–0.988) for Occupational Performance and 0.956 (95% CI: 0.911–0.979) for Occupational Satisfaction (both p < 0.001). Concurrent validity was partially supported by weak-to-moderate correlations between the COPM and the FIM at both the initial and final evaluations. Both COPM subscales showed significant improvements following inpatient rehabilitation (p < 0.001), with a mean change of 2.37 and 2.18 points for Occupational Performance and Occupational Satisfaction, respectively. Improvements of at least 2 points, a commonly used threshold for minimal important change in COPM scores, were observed in 51.6% and 41.9% of participants, respectively. Exploratory analyses showed no significant differences according to sex, stroke type, or affected body side. Conclusions: The Lithuanian version of the COPM demonstrated high test–retest reliability, evidence partially supporting concurrent validity, and responsiveness to change in individuals undergoing poststroke rehabilitation. These findings support its use as a client-centered outcome measure for evaluating occupational performance and satisfaction alongside standardized functional assessments.

Glioblastoma (GBM) remains highly lethal despite early therapeutic responses, as resistance inevitably emerges. While clinical studies show improvements in progression-free survival (PFS) during the early response (ER) phase, the molecular trajectory bridging ER and recurrent resistance (RR)-and the adaptive resistance programs temporally engaged during this transition- remain poorly understood. To dissect the dynamic molecular evolution underlying therapy resistance, patient-derived xenograft (PDX) models were treated with anti-VEGF therapy. Longitudinal proteogenomic profiling across multiple time points was performed to capture time-resolved molecular changes associated with the tumor response to the therapy. Longitudinal analyses revealed a dynamic, temporally evolving response trajectory, with an initial response phase (IRP) marked by neuronal-like remodeling, and a late response phase (LRP) characterized by mesenchymal transdifferentiation and metabolic adaptation. Proteomic and phosphoproteomic analyses identified the CTNNB1-NRG3-ERBB4 signaling axis as a key driver of neuronal-like remodeling during the IRP. Mechanistically, β-catenin activation upregulated NRG3, promoting postsynaptic scaffold remodeling, while pharmacological inhibition of β-catenin/CBP with PRI-724 disrupted this neuronal program and significantly extended survival in vivo. These findings place neuronal-like remodeling within a time-resolved framework of tumor adaptation to anti-VEGF therapy in GBM and highlight the CTNNB1-NRG3-ERBB4 axis as a tractable therapeutic target, providing a rationale for combination strategies to overcome anti-VEGF therapy failure.

Colorectal cancer (CRC) encompasses biologically diverse cellular phenotypes with distinct microRNA (miRNA) expression patterns. Assessing whether cell-model-derived alterations recur in extracellular vesicles (EVs) and human tumors may help prioritize candidates with broader relevance to CRC. We performed small RNA sequencing of non-malignant HCoEpiC cells, differentiated enterocyte-like Caco-2 cells, less differentiated HCT116 cells, and their corresponding EVs. miRNAs showing concordant dysregulation in both CRC cell lines relative to HCoEpiC, with greater absolute log2 fold changes in HCT116, were prioritized and evaluated in human colorectal tissues and TCGA-COAD/READ. Seven of 29 prioritized cellular miRNAs met the EV selection criteria. Of the 26 candidates measurable in the patient-tissue dataset, eight showed FDR-significant, directionally concordant differences between CRC and healthy colorectal tissues, including five concordantly dysregulated across cells, EVs, and patient tissues. Analysis of 11 matched TCGA tumor–non-tumor pairs reproduced reduced miR-30a-3p, miR-30c-2-3p, and miR-1271-5p and increased miR-140-5p expression. Target-based enrichment and exploratory miRNA-mRNA correlation analyses identified associations with CRC-relevant signaling and MYC-related, cell-cycle, DNA-repair, and metabolic programs. No significant associations with the evaluated clinicopathological features or overall survival were detected. Collectively, these findings identify a reproducible subset of CRC-associated miRNA alterations and highlight reduced miR-30a-3p and miR-30c-2-3p expression as a recurrent family-level pattern warranting mechanistic investigation.

Background/Objective: Influenza vaccination is recommended for patients at increased cardiovascular risk. Yet, despite Lithuania’s high cardiovascular mortality, it remains unclear whether uptake is higher among patients at greater cardiovascular risk, particularly those receiving secondary prevention. Vaccination uptake and its associated factors were assessed among statin users, a population at increased cardiovascular risk. Methods: A nationwide registry-based cohort study of Lithuanian statin users was conducted using national e-health records covering the 2020/21 to 2025/26 influenza seasons (1 September to 31 May). Patients were classified into primary- and secondary-prevention groups based on prescription indications coded according to ICD-10-AM. Factors associated with vaccination uptake were examined via multivariable logistic regression. Results: The final cohort included 812,086 unique statin users (81.6% primary, 18.4% secondary prevention). Crude uptake was higher among secondary-prevention (~21%) than primary-prevention patients (~14%; OR 1.73, 95% CI 1.71–1.75); after adjustment for age, prior vaccination and other covariates, the association was small (aOR 1.07, 95% CI 1.06–1.08). A documented prior influenza vaccination was strongly associated with vaccination (aOR 22.18, 95% CI 21.95–22.41). Statin non-persistence (aOR 0.76) and non-initiation (aOR 0.61) were associated with lower odds of vaccination. Conclusions: Influenza vaccination uptake only slightly differed among prevention groups and remained below the WHO 75% coverage target, suggesting that cardiovascular risk status may add little to vaccination uptake beyond age and vaccination history. Prior vaccination and statin treatment persistence were strongly associated with vaccination. This may reflect a shared pattern of engagement with preventive care, but engagement was not measured, and this interpretation remains a hypothesis. Whether bundling vaccination promotion with medication reviews, or involving pharmacists, would raise uptake in higher-risk patients needs to be tested.

Bereavement research has frequently focused on psychopathology, while comparatively less attention has been given to well-being as a component of mental health. This study is the first to examine mental health profiles based on ICD-11 Prolonged Grief (PG) symptoms, posttraumatic stress (PTS) symptoms, and well-being in a sample of Ukrainians bereaved during the full-scale Russian invasion. Participants were 290 adults (Mage = 34.3, SD = 9.1 years), who had lost a loved one on average 5.3 months earlier. Over a third (35%) had lost a partner or child, due to illness (43%) or war (40%). The majority of participants (55%) scored above the threshold of clinically relevant PG symptoms. Latent profile analyses identified three distinct mental health profiles: (1) low PG symptoms/low PTS symptoms/high well-being (13%), (2) moderate PG symptoms/low PTS symptoms/moderate well-being (57%), (3) high PG symptoms/low PTS symptoms/low well-being (30%). People evidencing the third profile were more likely to have experienced the loss of a close person (partner or child) and to have been forcibly displaced compared to people in other profiles. Notably, the distribution of these profiles differs from previous studies, where profiles marked by low symptoms and high well-being were typically most common. Moreover, PG and well-being appeared to lie on opposite ends of a single continuum rather than functioning as distinct dimensions, providing limited support for the dual-continua model. This pattern suggests that Ukrainians may be facing unique challenges due to ongoing war-related stressors. Identifying those most in need of support and highlighting potential intervention targets are particularly important in under-resourced populations where access to care is limited.

Representatives of five genera of the Lamiaceae family, such as Thymus, Satureja, Monarda, Ocimum, and Hyssopus, are especially appreciated for their valuable decorative features and the beneficial biological properties of their essential oils and extracts. In this study, the key morphological features of eight new cultivars (Monarda didyma L., Monarda bradburiana L. C. Beck, Satureja hortensis L., Satureja coerulea L., Thymus vulgaris L., Ocimum basilicum var. citriodorum L., and Hyssopus officinalis L.), cultivated firstly under the conditions of the central forest-steppe of Ukraine, as well as the chemical composition and antibacterial activity of their essential oils, were studied. The chemical composition of the essential oils obtained from the fresh aerial parts of the studied plants via hydrodistillation was evaluated by GC-MS. In addition, the screening tests of antibacterial activity against Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (ATCC 12228), Pseudomonas aeruginosa (ATCC 27853), Klebsiella pneumoniae (clinical isolate), and Escherichia coli (ATCC 25922) were performed using the disk diffusion method. Two essential oils, T. vulgaris and M. didyma, were rich in thymol (49.9% and 58.5%, respectively), and four essential oils (M. didyma, M. bradburiana, S. hortensis, and S. coerulea) were rich in carvacrol (49.4–69.9%). The essential oil of O. basilicum contained linalool, citral, and neral (38.7%, 12.6%, and 9.4%), whereas the essential oil of H. officinalis contained pinanone (51.3%) and pinocarvone (18.5%). All the tested essential oils exhibited strong antibacterial activity against S. aureus and S. epidermidis. The essential oils of M. didyma, M. bradburiana, S. hortensis, S. coerulea, T. vulgaris, and O. basilicum had strong antibacterial activity against E. coli as well. Our findings demonstrated that the studied essential oils are rich in characteristic terpenes and terpenoids, which are likely to induce their antimicrobial activity. The revealed morphological features, chemical composition and antibacterial activity of the essential oils highlight the need for further studies to assess the repeatability of results for these cultivars bred across other years on the same plots. Additionally, the studied plants have great potential for further research on the development of medicinal and cosmetic products with various biological properties.

Autoimmune bullous diseases (AIBD), Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN) and erythema multiforme (EM) often present with clinically similar features in the oral mucosa: classically widespread mucosal erosions or ulceration. Despite this, there are no formalized guidelines for the specific management of the oral manifestations of these conditions.