Biodentine, a tricalcium silicate cement, has emerged as a retrograde root-end filling material to promote periapical lesion (PL) healing after apicoectomy. However, its underlying mechanisms remain unclear. This study tested the hypothesis that Biodentine stimulates the osteogenic differentiation of mesenchymal stromal cells (MSCs) derived from PLs. The Biodentine extract (B-Ex) was prepared by incubating polymerized Biodentine in RPMI medium (0.2 g/mL) for three days at 37 °C. B-Ex, containing both released microparticles and soluble components, was incubated with PL-MSCs cultured in either a basal MSC medium or suboptimal osteogenic medium. Osteogenic differentiation was assessed by Alizarin Red staining and the expression of 20 osteoblastogenesis-related genes. Non-cytotoxic concentrations of B-Ex stimulated the proliferation of PL-MSCs and induced their osteogenic differentiation in a dose-dependent manner, with a significantly enhanced effect in suboptimal osteogenic medium. B-Ex upregulated most early and late osteoblastic genes. However, the differentiation process was prolonged, as indicated by the delayed expression of wingless-type MMTV integration site family member 2 (WNT2), bone gamma-carboxyglutamate protein (BGLAP), bone morphogenic protein-2 (BMP-2), growth hormone receptor (GHR), and FOS-like 2, AP-1 transcription factor subunit (FOSL2), compared with their expression under optimal osteogenic conditions. The stimulatory effect of B-Ex was primarily calcium dependent, as it was reduced by 85% when B-Ex was treated with the calcium-chelating agent EGTA. In conclusion, Biodentine promotes the osteogenic differentiation of PL-MSCs in a calcium-dependent manner, supporting its stimulatory role in periapical healing.

Background/Objectives: Mild traumatic brain injury (mTBI) is a leading cause of pediatric emergency department visits, particularly among children under three years old. Although computed tomography (CT) is the gold standard for diagnosing intracranial injuries, its use in young children poses radiation risks. Identifying reliable clinical indicators that justify CT imaging is essential for optimizing both patient safety and resource utilization. Objective: This study aimed to evaluate CT findings in children under three years of age with mTBI and no focal neurological deficits, as well as to identify clinical predictors associated with skull fractures and intracranial injuries. Methods: A retrospective analysis was conducted on 224 children under 36 months who presented with mTBI to a tertiary pediatric hospital from July 2019 to July 2024. Demographic data, injury mechanisms, clinical presentation and CT findings were evaluated. Univariate and multivariate regression analyses were performed to identify risk factors associated with skull fractures and intracranial injuries. Results: Falls accounted for 96.4% of injuries, with the majority occurring from heights of 0.5–1 m. The parietal region was the most frequently affected site (38%). Skull fractures were present in 46% of cases and were primarily linear (92.8%). Intracranial hematomas were identified in 13.8% of cases, while brain edema was observed in 7.6%. Significant predictors of skull fractures included age under 12 months (p < 0.001), falls from 0.5–1 m (p = 0.005), somnolence (p = 0.030), scalp swelling (p = 0.001) and indentation of the scalp (p = 0.016). Parietal bone involvement was the strongest predictor of both skull fractures (OR = 7.116, p < 0.001) and intracranial hematomas (OR = 4.993, p < 0.001). Conversely, frontal bone involvement was associated with a lower likelihood of fractures and hematomas. Conclusions: The findings highlight key clinical indicators that can guide decision-making for CT imaging in children with mTBI. Infants under 12 months, falls from moderate heights and parietal bone involvement significantly increase the risk of fractures and intracranial injuries. A more refined diagnostic approach could help reduce unnecessary CT scans while ensuring the timely identification of clinically significant injuries.

Background Because of the COVID-19 pandemic, people were recommended to implement new health behaviors into their daily routines to prevent the viral spread. The aim of this study was to investigate whether specific health behaviors, such as wearing face masks, taking immunity boosters and visiting risky places were associated with a higher level of stress due to COVID-19 in the general adult population. Method This cross-sectional study was conducted from September 1, 2020 to October 1, 2021 in eight randomly chosen cities of two Serbian speaking countries (Republic of Serbia and Republic of Srpska - Bosnia and Herzegovina). Participants filled a socio-epidemiologic questionnaire, COVID Stress Scales (CSS) and the Perceived Stress Scale (PSS). Results The study included 2,301 participants with an average age of 36.72 ± 13.82 years of whom 54.9% were female (p = 0.001). Most participants were healthy, highly educated, employed, married, non-smokers and consumed alcohol. The mean total CSS score was 32.7 ± 23.8 out of 144, suggesting a relatively low stress due to COVID-19. The mean PSS was 19.43 ± 5.05 out of 40 indicating slightly increased level of general stress. Participants who reported higher CSS scores were more likely to wear face masks, use immunity boosters, go to cafes and clubs, have chronic illnesses, have suspicious, but not proven contact with COVID-19 positive people, and use multiple sources of information about COVID-19. Conclusion Few participants experienced high levels of stress due to COVID-19. People who used face masks, immunity boosters and visited risky places reported a higher level of stress during the pandemic. Supplementary Information The online version contains supplementary material available at 10.1186/s41043-025-00833-2.

Tungsten disulfide (WS2) nanoparticles have emerged in the biomedical field as potential theranostic agents due to their unique properties, including biocompatibility. However, their impact on the immune response remains unexplored. This study aimed to evaluate the effects of inorganic fullerene-like WS2 (IF-WS2) nanostructures on human peripheral blood mononuclear cells (PBMCs) in vitro. The study investigated several parameters to evaluate the effects of IF-WS2 nanoparticles. Cytotoxicity was assessed by measuring cell viability, apoptosis, and necrosis. Internalization of IF-WS2 by PBMCs was analyzed using morphological and flow cytometric techniques. Proliferation was studied in CellTrace Far Red-prestained total PBMCs stimulated with phytohemagglutinin (PHA) and in isolated T cell cultures stimulated with CD3/CD28-coated beads. Additionally, the production of cytokines and chemokines was measured in culture supernatants of total PBMCs and T cells. IF-WS2 nanoparticles were non-cytotoxic up to a concentration of 200 µg/mL. Concentrations ≥25 µg/mL inhibited PHA-stimulated PBMC proliferation but did not affect T cell proliferation. Morphological and flow cytometric analysis demonstrated dose- and time-dependent internalization of IF-WS2 by macrophages. Additionally, IF-WS2 significantly reduced the production of pro-inflammatory cytokines (IL-1β, TNF-α, IL-8, MCP-1, and GRO-α) in PHA-stimulated PBMCs. Th1, Th17, and Th21 cytokines were downregulated, while Th2, Th9, and T regulatory cytokines were upregulated. In conclusion, this study demonstrated for the first time that pristine IF-WS2 nanoparticles, at non-cytotoxic concentrations, exhibit notable anti-inflammatory and immunomodulatory properties on activated PBMCs in vitro.

The aim of the study was to assess the seroprevalence of SARS‐CoV‐2 in the Republika Srpska, Bosnia and Herzegovina, after five waves of COVID‐19 and 1 year after introduction of vaccination to better understand the true extent of the COVID‐19 pandemic in the population of the Republika Srpska and role of vaccination in achieving herd immunity.

Introduction Alcoholic liver disease represents a growing global pandemic, particularly among younger men, and is one of the leading causes of premature death worldwide. Observing complications during the decompensation stage and monitoring disease progression dynamics using scoring systems are particularly important. Materials and methods This retrospective-prospective, descriptive, and analytical study included 123 male patients with a confirmed diagnosis of alcoholic liver cirrhosis, hospitalized at the Internal Medicine Clinic, University Clinical Centre of the Republic of Srpska in Banja Luka, Department of Gastroenterology and Hepatology. The study period spanned from January 2023 to January 2025, with the note that patient selection and monitoring began much earlier, in June 2021. After hospitalization, patients were followed monthly through a program of outpatient control examinations, with disease outcomes recorded. The study included all male patients over 18 years of age with a confirmed diagnosis of alcoholic liver cirrhosis and signed informed consent. Female patients and those with cirrhosis or other etiologies were excluded. For statistical data analysis, the Statistical Package for the Social Sciences (SPSS) version 29 (IBM Corp., Armonk, NY, USA) was used. The statistical analyses performed included median, standard deviation, analysis of variance, Student's t-test, chi-square test, and survival analysis. Results The mean age of the patients was 59.09±9.316 years. Most of them had anemia: 113 patients (91.86%) with decreased erythrocytes and 109 patients (88.62%) with decreased hemoglobin. Thrombocytopenia was observed in 104 patients (84.55%), while an increased mean corpuscular volume (MCV) was recorded in 68 patients (55.28%). Among biochemical parameters, the most common findings were increased bilirubin in 98 patients (79.67%), aspartate aminotransferase (AST) in 111 patients (90.24%), gamma-glutamyl transferase (GGT) in 109 patients (88.61%), and D-dimer in 110 patients (89.44%), while albumin levels were decreased in 107 patients (87.00%). Hyponatremia (decreased sodium) was observed in 63 patients (51.21%), and hypercalcemia (increased calcium) in 116 patients (94.30%). Jaundice was the most common external sign, present in 98 patients (79.67%), while ascites were noted in 86 patients (69.91%). Death during the first decompensation occurred in 31 patients (25.20%), of whom 17 (54.83%) died in the hospital. The leading cause of mortality is bleeding from esophageal varices. Conclusion Although a healthy liver performs over 200 distinct functions in the human body, a cirrhotic liver leads, one might say, to an even greater number of dysfunctions. This pathology is extremely complex, characterized by numerous complications and high treatment costs, which, despite all applied measures, do not ensure a favorable long-term prognosis without liver transplantation.

Background/Aim. Piclidenoson (CF101, IB-MECA), a selective agonist of the A3 adenosine receptor (A3AR), is used in clinical trials for the treatment of psoriasis. Emerging data from in vitro and in vivo studies suggest that piclidenoson possesses anti-inflammatory and immunomodulatory properties, but its action on human peripheral blood mononuclear cells (PBMCs) remains unknown. The aim of this study was to examine the anti-inflammatory effects of piclidenoson in a model of phytohaemagglutinin (PHA)-stimulated human PBMCs culture. Methods. Human PBMCs were isolated from the venous blood of healthy donors (n = 4) and treated with different concentrations of piclidenoson. Flow cytometry and the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) test were used to determine cell viability, while the MTT method and the carboxyfluorescein succinimidyl ester (CFSE) staining method were used to analyze the effect of picl idenoson on cell proliferation. Levels of tumor necrosis factor (TNF)-?, interleukin (IL)-6, IL-1?, IL-23, IL-36, IL-5, interferon (IFN)??, IL-17, and IL-10 were measured using a specific sandwich enzyme-linked immunosorbent assay (ELISA). Results. The results of cytotoxicity tests showed that the highest applied concentration of piclidenoson (1,500 nM) reduced the metabolic activity of PBMCs (p < 0.05) and increased the percentage of late apoptotic (p < 0.05) and necrotic cells (p < 0.01). Non-toxic concentrations (250, 500, and 1,000 nM) decreased the proliferation of PBMCs (p < 0.05) compared to the control cells. These concentrations also decreased the production of TNF-? (p < 0.001). Piclidenoson at concentrations of 250 and 1,000 nM reduced the production of IL-23 (p < 0.05) while the concentrations of 500 and 1,000 nM reduced the production of IL-36 (p < 0.05). Piclidenoson at 1,000 nM increased IL-1? production, while other concentrations decreased its production (p < 0.01). The highest concentration (1,000 nM) inhibited the production of IL-5 (p < 0.05) and IFN-? (p < 0.01) while all applied concentrations inhibited the production of IL-17 (p < 0.001). Furthermore, piclidenoson increased the production of IL-10 in all applied concentrations (p < 0.01). Conclusion. At non-toxic concentrations, piclidenoson exerts anti-inflammatory properties associated with the inhibition of proliferation and modulation of cytokine production in PHA-stimulated PBMCs culture.

Dapsone is a sulfone used in treating inflammatory skin conditions. Despite its widespread dermatological use, the pharmacological actions of dapsone remain poorly understood. Here, we examined how different aspects of neutrophil functions are affected by dapsone. Peripheral blood neutrophils from healthy donors were stimulated with phorbol-12-myristate-13-acetate (PMA), N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), or calcium ionophore (CaI) or primed with cytokines prior to stimulation, in the presence of different concentrations of dapsone (from 10 to 50 µg/mL), followed by analyses of their survival, phenotype, and functional properties. We found that dapsone at the concentration of 50 μg/mL induced a significant neutrophil apoptotic rate during 6 h and 18 h, while other concentrations were well tolerated compared to control non-treated cells. However, dapsone significantly decreased the induced oxidative burst of neutrophils at all non-cytotoxic concentrations. Additionally, dapsone showed a dose-dependent suppression of NETosis in activated neutrophils. The production of IL-8 by dapsone-treated neutrophils was decreased under both stimulated (fMLP) and primed (TNF-α/fMLP) conditions. Moreover, dapsone inhibited the expression of CD11b/CD18, CD66, and CD89 and reversed or significantly mitigated the downregulation of CD16, CD32, CD181, CD88, and CD62L on neutrophils after priming and fMLP stimulation. In conclusion, our results indicate the complexity of dapsone actions on neutrophil functions, extending previous knowledge on the suppression of oxidative burst and IL-8 production upon neutrophils’ activation. Suppressed NETosis and modulation of marker expression associated with different neutrophil functions under inflammatory conditions are new findings, not recognized previously.

<p><strong>Introduction. </strong>The COVID-19 pandemic has had a significant impact on the mental health of individuals with chronic diseases. Contributing factors include limited access to healthcare during lockdowns, fear of infection, and heightened stress due to poorer outcomes of COVID-19 infection in this population. The aim of this study was to examine the presence of depression, anxiety, and stress in the second year of the COVID-19 pandemic among individuals with pre-ex<br />isting cardiovascular, malignant, chronic respiratory diseases, or diabetes mellitus.<br /><strong>Methods. </strong>A cross-sectional study was conducted among the general population of the eastern region of Republic of Srpska during December 2021 and January 2022. Depression, anxiety, and stress were assessed using the DASS-21 scale, while data on comorbidities were collected through a questionnaire from an epidemiological population-genetic study conducted concurrently.&nbsp;<br /><strong>Results.</strong> A total of 1,372 participants from the eastern region of Republic of Srpska were included in the study, consisting of 40.0% males and 60.0% females. Participants were aged 20 years and older, with an average age of 50.6 years. The study found that depression, anxiety, and stress were statistically significantly more prevalent among participants with pre-existing cardiovascular or chronic respiratory diseases compared to those without such conditions. Additionally, participants with a history of malignant diseases or diabetes mellitus were significantly more depressed and anxious than&nbsp;<br />those without these conditions.<br /><strong>Conclusion. </strong>The findings of this study may contribute to the development of policies aimed at improving mental health and preventing mental disorders in individuals with comorbidities.</p>

Background: The COVID-19 pandemic has had a significant impact on the global economy and public health, disrupting various aspects of daily life. Apart from its direct effects on physical health, it has also significantly affected the overall quality of life and mental health. This study employed a path analysis to explore the complex association among multiple factors associated with quality of life, anxiety, and depression in the general population of the Republic of Srpska during the pandemic’s second year. Method: A cross-sectional study was conducted on a nationally representative sample (n = 1382) of the general population (adults aged 20+) during the second year of the COVID-19 pandemic in the Republic of Srpska, Bosnia, and Herzegovina. Assessment tools included the DASS-21 scale for depression, anxiety, and stress, along with the Brief COPE scale, Quality of Life Scale (QOLS), and Oslo Social Support Scale (OSSS-3). Sociodemographic factors and comorbidities were also assessed. Structural equation modeling was used to identify the direct and indirect links of various characteristics to quality of life, anxiety, and depression. Results: This study revealed a considerable prevalence of anxiety and depression symptoms (27.5% and 20.9%, respectively), with quality of life playing a significant mediating role. The constructed path model accounted for 33.1% of moderate to severe depression and 79.5% of anxiety. Negative coping was directly linked to anxiety and indirectly to depression via anxiety, while the absence of positive coping had both direct and indirect paths (through quality of life) on depression. Among variables that directly affected depression, anxiety had the highest effect. However, the bidirectional paths between anxiety and depression were also suggested by the model. Conclusions: Pandemic response strategies should be modified to effectively reduce the adverse effects on public mental health. Further research is necessary to assess the long-term effects of the pandemic on mental health and to analyze the contributing factors of anxiety and depression in the post-COVID period.