Search Results (39)

Background: Oral diseases such as periodontitis, dental infections, and oral dysbiosis have been increasingly associated with systemic conditions. Emerging evidence suggests a potential relationship between oral health and neurological disorders, including brain abscesses, structural brain alterations, and gliomas. However, the strength and mechanisms of these associations remain incompletely understood. Objective: To systematically review clinical, neuroimaging, genetic, and mechanistic evidence linking oral diseases with brain pathologies. Methods: A systematic literature search was conducted in PubMed, Scopus, Web of Science, and EBSCO, with complementary screening of SciELO, Redalyc, and LILACS databases. Studies evaluating associations between oral diseases (periodontitis, dental infections, caries, or oral microbiota alterations) and neurological outcomes were considered. Eligible study designs included observational clinical studies, Mendelian randomization analyses, neuroimaging studies, and experimental investigations. Seventeen studies met the inclusion criteria. Due to the substantial heterogeneity in study designs, outcomes, and effect metrics, quantitative meta-analysis was not feasible. Findings were therefore synthesized using a structured narrative approach following PRISMA guidelines. Results: Clinical studies consistently identified odontogenic infections as a relevant source of brain abscesses, frequently originating from chronic or clinically silent dental foci. Neuroimaging and genetic studies reported associations between poor oral health indicators and structural brain alterations, including reduced cortical thickness and white matter abnormalities. Experimental investigations suggested potential biological mechanisms involving microbial dissemination, systemic inflammation, and immune modulation. Virulence factors from Porphyromonas gingivalis have been shown to induce inflammatory signaling pathways and immune checkpoint activation in glioma cells. Conclusions: The current evidence suggests a possible association between oral diseases and several brain pathologies. Although causality cannot be established, the findings highlight the importance of oral health as a potentially modifiable factor relevant to neurological health. Further longitudinal and mechanistic studies are required to clarify these relationships. Full article

Background: Immersive technologies are increasingly used to support interprofessional education and team training in healthcare. Holographic display technology (HDT) offers a novel approach for delivering distributed, simulation-based TeamSTEPPS training; however, evidence regarding its short-term feasibility remains limited. Methods: This mixed-methods pilot feasibility study examined the acceptability and limited efficacy (defined as learning satisfaction and self-reported gains) of HDT for interprofessional TeamSTEPPS-based team training across two geographically distributed campuses. Quantitative measures assessed changes in UTAUT-informed constructs, including attitude toward technology use (ATU) and behavioral intention (BI), while qualitative focus groups explored learner experiences and perceptions. Results: Of 64 participants, 47 consented to analysis. Quantitative analyses demonstrated post-training improvements in key technology-acceptance constructs, including significant gains in ATU and strengthened alignment between BI and UTAUT predictors. Qualitative findings reflected high learner engagement and perceived educational value, alongside practical considerations related to technical and instructional coordination. Conclusions: HDT was feasible for assessment of short-term foci of acceptability and perceived limited efficacy through the delivery of interprofessional TeamSTEPPS training, with observed gains in ATU and BI. These findings inform future assessment of long-term feasibility foci, including implementation studies examining the role of holographic simulation in advancing interprofessional education, healthcare workforce development, and the quality of healthcare delivery. Full article

Endometritis features an inflammatory milieu in the endometrium, accompanied by the recruitment of immunocompetent cells, including mast cells (MCs). The mechanisms underlying MC involvement in chronic endometritis (CE) and fibrous niche formation remain poorly understood, particularly regarding spatial intercellular interactions in situ. In this study, we used multiplex immunohistochemistry and quantitative immunofluorescence analysis to map the spatial phenotype of MC distribution. Standard histochemical techniques, monoplex and multiplex immunohistochemical staining technologies, light-field microscopy, epifluorescence, and confocal microscopy with multispectral imaging, combined with quantitative immunofluorescence analysis with AI application, were used to identify the spatial phenotyping of quantitative and qualitative features of the endometrial MC population in CE. The increased intensity of endometrial inflammation was accompanied by a rise in the profile of MC content in the endometrium; this accounted for a 0.014% increase in the control and 0.067%, 0.113%, and 0.206% increases in mild, moderate, and severe CE, respectively. We are the first to map the number of MCs that demonstrated loci of accumulations in the endometrium coinciding with foci of fibrous changes. The number of these foci correlated with the severity of chronic endometritis and the development of clinical signs. The frequency of juxtacrine and paracrine MC colocalization with other immunocompetent cells increased with increased CE activity and fibrotic changes: For CD8⁺ lymphocytes, colocalization increased from 4.6% in the control to 11.6%, 18.5%, and 28.0% in mild, moderate, and severe CE, respectively. For monocytes, colocalization increased from 5.6% in the control to 18.7%, 26.8%, and 28.8% in mild, moderate, and severe CE, respectively. For type 1 macrophages, colocalization increased from 5.6% in the control to 13.5%, 17.4%, and 24.6% in mild, moderate, and severe CE, respectively. For type 2 macrophages, colocalization increased from 3.4% in the control to 9.6%, 9.1%, and 21.5% in mild, moderate, and severe CE, respectively. Spatial patterns of juxtacrine and paracrine MC interactions with other immune cells may provide diagnostic algorithms for chronic endometritis, enabling targeted therapy and preventing fibrotic changes. Full article

High-grade serous ovarian cancer (HGSOC) is the most commonly diagnosed ovarian cancer subtype. Approximately half of all patients diagnosed with HGSOC are deficient in homologous recombination (HR), harbor BRCA1/2 mutations, and are treated with poly (ADP-ribose) polymerase (PARP) inhibitors (PARPis). FDA-approved PARPis Olaparib, Niraparib, and Rucaparib all contribute to adverse effects in patients due to their poly-pharmacological properties. This feature necessitates investigation of global protein responses to PARPi treatment beyond DNA repair in the context of BRCA mutational status and HR deficiency. We sought to determine the landscape of differential PARPi-induced proteomes in HGSOC cells exhibiting different BRCA1/2 mutational statuses. Here, we applied immunofluorescence microscopy to detect γH2AX, Rad51, and geminin foci as markers of DNA damage and repair upon treatment of HGSOC cells with IC₅₀ doses of PARPis. Global proteome perturbations upon PARPi treatment were measured using quantitative mass spectrometry-based proteomics. The proteomic data highlighted cell line effects, masking high-dose PARPi treatment response. Interrogation of PARPi response within biological pathways identified through gene set enrichment analysis (GSEA) revealed significant changes to proteins involved in Epithelial–Mesenchymal Transition (EMT), E2F targets, and cholesterol homeostasis. Our study establishes proteomic evidence supporting the poly-pharmacological characteristics of Niraparib, Olaparib, and Rucaparib in HGSOC cells. Full article

This study maps the landscape of initial teacher education (ITE) research in Central Asia and its positioning within global academic discourse between 2004 and 2024. Drawing on a systematic scoping review of 144 publications conducted using the PRISMA-ScR protocol, it analyses publication trends, methodological approaches and thematic foci. The findings indicate that although Central Asia’s contributions to global ITE discourse remain limited, scholarly output is growing, particularly in Kazakhstan, while publications from Tajikistan and Turkmenistan are notably absent. Most studies are empirical and predominantly quantitative, with a strong thematic focus on curriculum-related areas, with limited attention to research and practicum in ITE programmes, teaching practices of teacher educators and educational reform and policies in the field, including issues of equity. By critically assessing these trends, the study identifies key gaps and proposes directions for future research, contributing to a more coherent and connected body of ITE scholarship in and on Central Asia. As the first synthesis of ITE research across the region, it offers a foundation for comparative analysis and cross-national dialogue on teacher education reform. Full article

Background: Hyperreflective retinal foci (HRF) are small, discrete, hyperreflective elements observed in the retina using optical coherence tomography (OCT). They appear in many retinal diseases and have been linked to disease progression, treatment response, and prognosis. However, their definition and clinical use vary widely, not just between different diseases, but also within a single disorder. Methods: This perspective is based on a review of peer-reviewed studies examining HRF across different retinal diseases. The studies included analyzed HRF morphology, distribution, and clinical relevance using OCT. Particular attention was given to histopathological correlations, disease-specific patterns, and advancements in automated quantification methods. Results: HRF distribution and features vary with disease type and even within the same disease. A variety of descriptions have been proposed with different characteristics in terms of dimensions, reflectivity, location, and association with back shadowing. Automated OCT analysis has enhanced HRF detection, enabling quantitative analysis that may expand their use in clinical practice. However, differences in software and methods can lead to inconsistent results between studies. HRF have been linked to microglial cells and may be defined as neuro-inflammatory cells (Inflammatory, I-HRF), migrating retinal pigment epithelium cells (Pigmentary, P-HRF), blood vessels (Vascular, V-HRF), and deposits of proteinaceous or lipid elements leaking from vessels (Exudative, E-HRF). Conclusions: HRF are emerging as valuable imaging biomarkers in retinal diseases. Four main types have been identified, with different morphological features, pathophysiological origin, and, therefore, different implications in the management of retinal diseases. Advances in imaging and computational analysis are promising for their incorporation into personalized treatment strategies. Full article

Lactoferrin (LF) is an iron-binding glycoprotein of the transferrin family and has been suggested to have a variety of biological functions, including anticancer activity. However, the effects of LF and its mechanisms in anticancer therapies, especially in radiotherapy against cancer cells under hypoxic conditions, are not well-determined. In this study, we focused on the molecular mechanisms of LF functions in cells under hypoxic conditions. High-dose LF treatment showed cytotoxic activity in a variety of cells, including both non-cancer and cancer cells. Interestingly, hypoxic treatment increased the sensitivity to LF in some cancer cells but decreased it in non-cancer cells. LF treatment also altered sensitivity to radiation treatment: LF significantly increased the viability of irradiated KD non-cancer cells under hypoxic conditions but decreased that of HSC2 cancer cells. These effects were only observed when LF was treated within 3 h of irradiation, but not before irradiation. Importantly, knockdown of HIF1A counteracted these effects in both cell lines. Measurements of ROS activity showed that LF decreased ROS production in KD cells but increased it in HSC2 cells, resulting in a decrease in γH2AX foci in KD cells but an increase in HSC2 cells. RNA-seq and gene set enrichment analysis showed that LF treatment regulated gene expression related to the cell cycle, apoptosis, inflammation, and the NRF2 antioxidant signaling pathway. Quantitative RT-PCR confirmed the downregulation of the pro-apoptotic gene ASC in KD cells and the NRF2-regulated genes in HSC2 cells by LF treatment. Knockdown experiments confirmed the role of ASC in irradiated KD cells and NRF2 in irradiated HSC2 cells with LF treatment. In conclusion, lactoferrin was shown to affect radiation treatment by regulating apoptosis and NRF2 signaling in a cell type-specific manner under hypoxic conditions, suggesting its potential application as a protector or sensitizer for radiation therapy. Full article

In hot and humid work environments, construction workers can experience heat stress and heat-related illnesses (HRIs). While several studies have investigated engineering and administrative control methods to prevent certain heat stress risk factors, a comprehensive understanding of all existing risk factors and their corresponding control strategies is still lacking. It is crucial to identify gaps in current control strategies and develop a safety management framework for effective heat stress control by implementing existing measures. In addition, the effectiveness of the most common control strategies must be rigorously evaluated to ensure their efficacy and to guide future research aimed at enhancing these strategies or developing more effective ones. This study employed a mixed literature review methodology to address this knowledge gap. A structured literature review investigated and synthesized heat stress risk factors and control methods to find the gaps in control options to address underestimated risk factors. Furthermore, a comprehensive systematic literature review, including trend analysis, scientometric analysis, and meta-analysis, determined research foci and evaluated the effectiveness of the heat stress control methods. The scientometric analysis identified 11 clusters, encompassing key research themes such as environmental risk factors (e.g., high-temperature environments, climate change), administrative controls (e.g., work–rest schedules, climate change risk assessment), and personal interventions (e.g., cooling vests and sleep-related strategies). These findings highlight that the most commonly studied control methods are cooling vests, work–rest schedules, and cooling interventions. According to these results and the availability of quantitative results, the meta-analysis evaluated nine datasets of reductions in core body temperature by using types of cooling vests and anti-heat-stress uniforms and established the significant effectiveness of this control strategy in mitigating heat stress with a medium effect size. Moreover, five potential research studies have been identified to address gaps in control strategies for certain underestimated risk factors, including leveraging sensor technologies, conducting control training, dynamic work–rest schedules, using cutting-edge PPE, and governmental initiatives. Insights gained from this study enhance decision making for resource allocation, selection of control options, and intervention prioritization within a heat-stress-control framework based on the safety management system. The findings also highlight the effectiveness of cooling vests and areas that need to be developed, and evaluate potential heat-stress-control methods in construction. Full article

Light is a crucial environmental factor for plant growth and development, and the light required for plant development on Earth mainly comes from solar radiation. Light not only affects the photomorphogenesis of plants as a trigger signal but also has an important influence on the whole development of plants. The study of photoperiod regulation of plant flowering is crucial in agricultural practice, as it directly affects plant variety selection, introductory adaptation, and yield stability. In this paper, we used the Bibliometrix package in R Studio, VOSviewer, and Citespace to bibliometrically and statistically analyze 3919 publications in the Web of Science core ensemble database from 2000 to 2023 and to explore the progress and trends in the study of photoperiodic regulation of plant flowering. Literature visualization techniques were used to analyze the annual quantitative distribution of the studies in the dataset, and co-occurrence analysis of collaboration between authors, co-occurrence analysis of collaboration between organizations, co-citation analysis, keyword co-occurrence analysis, and identification of topic evolution were also performed. The results show that the number of publications on photoperiodic regulation of plant flowering is increasing every year, showing a significant diversification and globalization trend in this research area. Growth, gene expression, and Arabidopsis thaliana are the most popular research areas in this field. Flowering gene networks and signaling pathways in the photoperiodic pathway, systems biology and multi-omics, environmental adaptation studies, and cross-species comparisons are current research hotspots. The thematic evolution suggests that environmental change, crop improvement and sustainable agriculture, light quality, and biological clock regulation may be foci of future research. This study reveals the research trends in photoperiodic regulation of plant flowering over the past 23 years and the areas where more research inputs are needed in the future, aiming to offer guidance for future research endeavors in the field of photoperiodic regulation of plant flowering. Full article

Background and Objectives: This study presents a retrospective analysis of 26 autopsy cases from a single centre, primarily focusing on forensic cases, with a majority of male individuals. Materials and Methods: We systematically analysed autopsy reports and cardiac tissue slides using haematoxylin-eosin stain and immunohistochemistry for CD3, CD163, and IL-6. The histological assessment evaluated key variables such as inflammation severity, necrosis, and background changes using a standardised grading system. Quantitative analysis of immunohistochemical markers was performed, calculating the percentage of positively stained cells within the inflammatory infiltrate. Results: The average age was 51.6 years, slightly skewed towards older males. The fatalities varied widely, with sudden death and drug abuse being the most common conditions linked to myocarditis findings on histological examination. A strong correlation was found between the severity of inflammation (measured by size within a myocardium section) and the scoring system based on the number of inflammatory foci per section (p ≤ 0.001). Most cases showed mild to minimal fibrosis, with some exhibiting moderate to severe fibrosis, arteriosclerosis, and myocyte hypertrophy. The presence of protein CD3 in the inflammatory infiltrate revealed a moderate inverse correlation between the CD3 values and the severity of inflammation and necrosis, and a strong inverse correlation with neutrophil levels. CD3 levels were higher in sudden death cases and lower in cases with numerous inflammatory foci, highlighting the discreet nature of lymphocytic myocarditis. Macrophage presence, assessed using CD163, showed a moderate inverse correlation with neutrophil levels and significant differences between sudden death and non-sudden death cases. Macrophage-rich inflammation was observed in cases with pneumonia/bronchopneumonia-associated lesions. IL-6 expression showed a moderate direct correlation with inflammation severity (p = 0.028), severity of necrosis (p = 0.005), and the number of inflammatory foci per section (p = 0.047). A moderate inverse correlation was found between CD3 and IL-6 expression (p = 0.005). Conclusions: These findings highlight the need for a unique immunohistochemical approach in forensic cases of myocarditis, differing from guidelines for endomyocardial biopsies due to diverse inflammatory cells. The study suggests exploring inflammatory chemokines within myocarditis foci for their significance in clinical scenarios. Specifically, IL-6, a crucial pro-inflammatory interleukin, correlated significantly with the severity of inflammation and necrosis (p < 0.05). This study provides novel and valuable insights into the histopathological and immunological markers of myocarditis in autopsy cases. Full article

Background: Cellular senescence in response to ionizing radiation (IR) limits the replication of damaged cells by causing permanent cell cycle arrest. However, IR can induce pro-survival signaling pathways that reduce the extent of radiation-induced cytotoxicity and promote the development of radioresistance. The differential incorporation of histone variant H2A.J has profound effects on higher-order chromatin organization and on establishing the epigenetic state of radiation-induced senescence. However, the precise epigenetic mechanism and function of H2A.J overexpression in response to IR exposure still needs to be elucidated. Methods: Primary (no target, NT) and genetically modified fibroblasts overexpressing H2A.J (H2A.J-OE) were exposed to 20 Gy and analyzed 2 weeks post-IR for radiation-induced senescence by immunohistochemistry and immunofluorescence microscopy. Transcriptome signatures were analyzed in (non-)irradiated NT and H2A.J-OE fibroblasts by RNA sequencing. Since H2A.J plays an important role in the epidermal homeostasis of human skin, the oncogenic potential of H2A.J was investigated in cutaneous squamous cell carcinoma (cSCC). The tissue microarrays of cSCC were analyzed for H2A.J protein expression pattern by automated image analysis. Results: In response to radiation-induced DNA damage, the overexpression of H2A.J impairs the formation of senescence-associated heterochromatin foci (SAHF), thereby inhibiting the SAHF-mediated silencing of proliferation-promoting genes. The dysregulated activation of cyclins and cyclin-dependent kinases disturbs cell cycle arrest in irradiated H2A.J-OE fibroblasts, thereby overcoming radiation-induced senescence. Comparative transcriptome analysis revealed significantly increased WNT16 signaling in H2A.J OE fibroblasts after IR exposure, promoting the fundamental mechanisms of tumor development and progression, including the activation of the epithelial–mesenchymal transition. The quantitative analysis of cSCCs revealed that undifferentiated tumors are associated with high nuclear H2A.J expression, related with greater oncogenic potential. Conclusion: H2A.J overexpression induces radioresistance and promotes oncogenic transformation through the activation of WNT16 signaling pathway functions. H2A.J-associated signatures may improve risk stratification by identifying patients with more aggressive cSCC who may require radiotherapy with increased doses. Full article

Neuroimaging studies using autobiographical recall methods investigated the neural correlates of happy autobiographical memories (AMs). The scope of the present activation likelihood estimation (ALE) meta-analysis was to quantitatively analyze neuroimaging studies of happy AMs conducted with autobiographical recall paradigms. A total of 17 studies (12 fMRI; 5 PET) on healthy individuals were included in this meta-analysis. During recall of happy life events, consistent activation foci were found in the frontal gyrus, the cingulate cortex, the basal ganglia, the parahippocampus/hippocampus, the hypothalamus, and the thalamus. The result of this quantitative coordinate-based ALE meta-analysis provides an objective view of brain responses associated with AM recollection of happy events, thus identifying brain areas consistently activated across studies. This extended brain network included frontal and limbic regions involved in remembering emotionally relevant positive events. The frontal gyrus and the cingulate cortex may be responsible for cognitive appraisal processes during recollection of happy AMs, while the subthalamic nucleus and globus pallidus may be involved in pleasure reactions associated with recollection of happy life events. These findings shed light on the neural network involved in recalling positive AMs in healthy individuals, opening further avenues for future research in clinical populations with mood disorders. Full article

In this study, the results of evaluating the acute toxicity of Bisphenol A on Danio rerio are presented, encompassing peripheral blood parameters, the composition of hematopoietic cells of erythroid and myeloid lines in the head kidney, and data from histological studies. The LC50 values of Bisphenol A for adult zebrafish individuals for 12, 24, and 48–96 h were determined, which were 18.04, 7.55, and 6.22 mg/L, respectively. The study includes data on the morphology and quantitative frequency of specific cells in the hematopoietic tissue of the head kidney, along with the consideration of adaptive mechanisms in hematopoiesis under BPA exposure. The application of polynomial regression analysis to reveal the concentration–effect relationship for some hematological and histological parameters was demonstrated. Significant increases in the frequency of erythrocyte nuclear abnormalities were observed at BPA concentrations of 6 and 8 mg/L, which indicates a genotoxic effect. BPA’s impact on fish peripheral blood parameters manifested as an increase in the number of erythrocytes (RBC) and immature erythrocytes, as well as a decrease in the number of lymphocytes. The most notable pathological changes in the head kidney’s hematopoietic tissue included circulatory disturbances and the formation of inflammation/degradation foci, as confirmed by histopathologic indices. At BPA concentrations of 2 and 4 mg/L, the observed changes were compensated for by hematopoietic adaptation mechanisms; however, at concentrations of 6 and 8 mg/L, acute systemic toxicity was evident. Full article

In the nucleus, distinct, discrete spots or regions called “foci” have been identified, each harboring a specific molecular function. Accurate and efficient quantification of these foci is essential for understanding cellular dynamics and signaling pathways. In this study, we present an innovative automated image analysis method designed to precisely quantify subcellular foci within the cell nucleus. Manual foci counting methods can be tedious and time-consuming. To address these challenges, we developed an open-source software that automatically counts the number of foci from the indicated image files. We compared the foci counting efficiency, velocity, accuracy, and convenience of Foci-Xpress with those of other conventional methods in foci-induced models. We can adjust the brightness of foci to establish a threshold. The Foci-Xpress method was significantly faster than other conventional methods. Its accuracy was similar to that of conventional methods. The most significant strength of Foci-Xpress is automation, which eliminates the need for analyzing equipment while counting. This enhanced throughput facilitates comprehensive statistical analyses and supports robust conclusions from experiments. Furthermore, automation completely rules out biases caused by researchers, such as manual errors or daily variations. Thus, Foci-Xpress is a convincing, convenient, and easily accessible focus-counting tool for cell biologists. Full article

Experimental autoimmune uveitis (EAU) is the most commonly used animal model to study the progression of chronic uveitis and to test various therapies to treat the disease. However, to accurately evaluate the effectiveness of such treatments, a grading system that combines the latest imaging techniques with definitive quantitative grading thresholds is required. This study aimed to develop a comprehensive grading system that objectively evaluates EAU progression in C57BL/6J mice. EAU was induced following immunisation with interphotoreceptor retinoid-binding protein (IRBP) and pertussis toxin. Weekly fundus and optical coherence tomography (OCT) images were acquired over 12 weeks using a Micron IV imaging system. Each mouse was graded (between 0 to 4) based on changes seen on both the fundus (optic disc, retinal blood vessels and retinal tissue) and OCT (vitreous and retinal layers) images. A total EAU response (with a maximum score of 48) was calculated for each mouse based on the sum of the individual scores each week. Analysis of the clinical scores depicted a gradual increase in inflammatory signs including optic disc and vascular swelling, leukocyte infiltration in the vitreous, lesions in the retina and formation of granulomas and hyper-reflective foci in the retinal layers in EAU mice, with most signs reaching a plateau towards the end of the study period. Development of these signs into sight-threatening complications such as optic disc atrophy, structural damage to the retina and subretinal oedema were noted in 80–90% of mice suggesting consistent disease induction. Overall, a comprehensive and objective grading system encompassing all pathologies occurring in EAU mice was developed to enhance the preclinical evaluation of novel uveitis treatments. Full article