Bosnian Journal of Basic Medical Sciences (BJBMS)
Not a member yet
1863 research outputs found
Sort by
In silico analysis reveals distinct changes in markers of epithelial to mesenchymal transition in glioma subtypes
Full text linkEpithelial to mesenchymal transition (EMT) plays a critical role in tumor progression and metastasis, including in gliomas. To examine and interpret data on major genes involved in EMT and associate their changes with low-grade (LGG) and/or high-grade (HGG) gliomas, data from the cBioPortal—a publicly available database for tumor genomics and transcriptomics, were collected for 13 genes: CDH1, CDH2, CTNNB1, LEF1, NOTCH1, SNAI1, SNAI2, SOX2, TJP1/ZO1, TWIST1, VIM, ZEB1, and ZEB2. The dataset included mutations, copy number alterations (CNA), and changes in transcript levels reported for each gene. The genes were additionally validated by gene expression on the GlioVis portal, STRING protein network analysis, survival analysis, and experimentally with qRT-PCR. Glioblastoma and diffuse glioma harbored changes in all 13 analyzed genes, while anaplastic oligodendroglioma and anaplastic astrocytoma in 46.15%, oligodendroglioma in 23.08%, and oligoastrocytoma in 15.38%. NOTCH1 and SOX2 were most affected by changes. The NOTCH1 gene was statistically more frequently changed compared to CDH1, CTNNB1, and ZEB1 (p < 0.05). The virtual study showed that alterations in NOTCH1 and LEF1 were associated with LGG, while alterations in CDH1, CTNNB1, TJP1, TWIST1, SOX2, VIM, ZEB1, and ZEB2 were associated with HGG. Differential expression analysis stratified for IDH1 mutations showed that IDH1-mutant glioblastoma had significantly lower CDH2, LEF1 and SNAI1 expression, and higher ZEB1. Gene expression in different glioblastoma subtypes showed that the TJP1/ZO1 gene was associated with the classical subtype, while ZEB2 was associated with the proneural subtype. qRT-PCR confirmed GlioVis mRNA expression data for NOTCH1, SOX2, CDH1, CTNNB1, TJP1/ZO-1, VIM, TWIST1, and partially for SNAI1 (SNAIL), SNAI2, and CDH2. Our study shows consistent changes in genes involved in EMT in gliomas of different grades. Additional research is needed to confirm the knowledge brought by this study.
Body weight and BMI variability linked to dementia risk: A meta-analysis
Full text linkEmerging evidence suggests that fluctuations in body weight (BW) or body mass index (BMI), independent of average levels, may influence dementia risk. However, the association between intra-individual variability in BW or BMI and incident dementia remains unclear. This meta-analysis aimed to clarify this relationship. A systematic search of PubMed, Embase, and Web of Science was conducted through March 25, 2025, to identify longitudinal observational studies reporting dementia outcomes in relation to BW or BMI variability. Relative risks (RRs) comparing the highest versus lowest variability categories were pooled using a random-effects model. Subgroup and sensitivity analyses were performed to explore heterogeneity and assess the robustness of the results. Nine cohort studies (10 datasets; 4,232,666 participants) were included. Overall, high BW or BMI variability was associated with a significantly increased risk of dementia (RR = 1.36, 95% CI: 1.27–1.46; p < 0.001; I² = 84%). The association was consistent for both BW (RR = 1.45) and BMI (RR = 1.34) variability. Subgroup analyses showed stronger associations in prospective studies than in retrospective ones, and in studies that did not adjust for baseline BW/BMI compared to those that did (p for subgroup difference < 0.05). Associations remained robust in sensitivity analyses and across dementia subtypes, including Alzheimer’s disease and vascular dementia. No significant publication bias was detected (Egger’s test, p = 0.22). In conclusion, greater intra-individual variability in BW or BMI may be independently associated with increased dementia risk. These findings underscore the importance of maintaining weight stability in mid-to-late life as a potential preventive strategy for dementia
Letter regarding "Association between triglyceride-glucose (TyG) index and risk of depression in middle-aged and elderly Chinese adults: Evidence from a large national cohort study."
Full text linkThis correspondence addresses the recent study by Xu et al. examining the relationship between the triglyceride-glucose (TyG) index and depression in older Chinese adults. The study\u27s identification of a J-shaped association between TyG levels and depressive symptoms adds meaningful insight into the connection between metabolic health and mental well-being. However, when considered alongside other findings, including those using combined indices such as TyG-BMI and TyG-WHtR, the results suggest that a broader, multidimensional approach may offer greater predictive value. Supporting studies have linked these composite measures not only to depression but also to wider metabolic and cardiovascular risks. Additionally, other reviews highlight the potential link between TyG and more severe psychiatric conditions. The letter emphasizes the need for further research, especially longitudinal and interventional studies, to clarify causal relationships and explore whether improving metabolic health can help prevent or reduce depressive symptoms. The authors encourage continued exploration of metabolic indicators not just as risk markers but as possible targets for intervention.
Secreted frizzled-related protein 4 (sFRP4) in cancer – Dual roles in tumorigenesis and therapeutic potential: A review
Full text linkSecreted Frizzled-Related Protein 4 (sFRP4), the largest member of the Secreted Frizzled-Related Protein (sFRP) family, contains two functional domains: a cysteine-rich domain (CRD) homologous to the Wnt-binding region of Frizzled (FZD) receptors and a netrin-like (NTR) domain structurally similar to axonal guidance proteins. By modulating the Wingless/Integrated (Wnt) signaling pathway, sFRP4 regulates essential cellular processes including proliferation, differentiation, apoptosis, and tissue homeostasis. This review aims to provide a comprehensive overview of the dualistic roles of sFRP4 in cancer, highlighting its tumor-suppressive and tumor-promoting functions, underlying molecular mechanisms, and therapeutic potential. A systematic literature search was conducted in PubMed and Web of Science databases (1996–2025) using predefined keywords, and from 277 identified publications, 47 studies were included that comprised clinical data, in vitro cell models, and in vivo experimental systems. Findings demonstrate that sFRP4 frequently acts as a tumor suppressor by sequestering Wnt ligands, suppressing cancer stem cell-like properties, reprogramming tumor metabolism, inhibiting angiogenesis, and enhancing chemosensitivity. Its downregulation is often driven by promoter hypermethylation or repression mediated by microRNAs (miRNAs). Conversely, in gastrointestinal and prostate cancers, sFRP4 is frequently upregulated, where it promotes Wnt pathway activation, invasion, stemness, chemoresistance, and reshaping of the tumor immune microenvironment. Mechanistic insights indicate that post-translational modifications and nuclear localization of sFRP4 further contribute to its paradoxical context-dependent functions. In conclusion, sFRP4 exerts dual roles in tumorigenesis, acting either as a tumor suppressor or promoter depending on tissue type, tumor microenvironment, and regulatory mechanisms. This complexity underscores both the challenges and opportunities of targeting sFRP4 in oncology, and future therapeutic strategies incorporating recombinant proteins, synthetic peptides, and nanoparticle-based delivery systems hold promise for harnessing its anti-tumor potential while overcoming resistance mechanisms
SMARCA4 deficiency in small cell lung cancer: A case report and narrative review of the literature
Full text linkSWItch/sucrose non-fermentable (SWI/SNF) is a large protein complex with a central role in chromatin remodeling and genome transcription. The catalytic subunits of the SWI/SNF related BAF chromatin remodeling complex subunit ATPase 2 (SWI/SNF SMARCA2; also called BRM) and SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4 (SMARCA4; also called BRG1) are encoded by the SMARCA2 and SMARCA4 genes, respectively, and are mutually exclusive. Loss of either SMARCA2 and/or SMARCA4 has been previously reported in several types of malignant solid tumors of the gastrointestinal and genitourinary tract. So far, their absence in non-small cell lung cancer (SCLC) has been observed in a series of studies involving primary tumors and cell lines, where it is associated with loss of differentiation and heightened tumorigenic potential leading to an unfavorable prognosis. SMARCA2 and SMARCA4 deficiency is frequent in solid predominant adenocarcinomas and tumors with low levels of bronchial epithelial markers, including thyroid transcription factor 1. A rare case of SMARCA4 deficiency in SCLC is described. A 57-year-old male patient, with no medical history of past illness, was admitted to our center for the investigation and management of a space-occupying lesion in the right upper lung lobe with tracheal and mediastinal infiltration. Biopsy of a lymph node in the right supraclavicular region was diagnostic for SCLC with regional loss of SMARCA4. The patient demonstrated progressive respiratory failure and clinical deterioration and eventually deceased despite intubation and transfer to the intensive care unit. This case indicates that SMARCA4-deficient SCLC may present with an aggressively deteriorating phenotype with poor outcomes for the patients
Deep learning approach based on a patch residual for pediatric supracondylar subtle fracture detection
Full text linkSupracondylar humerus fractures in children are among the most common elbow fractures in pediatrics. However, their diagnosis can be particularly challenging due to the anatomical characteristics and imaging features of the pediatric skeleton. In recent years, convolutional neural networks (CNNs) have achieved notable success in medical image analysis, though their performance typically relies on large-scale, high-quality labeled datasets. Unfortunately, labeled samples for pediatric supracondylar fractures are scarce and difficult to obtain. To address this issue, this paper introduces a deep learning-based multi-scale patch residual network (MPR) for the automatic detection and localization of subtle pediatric supracondylar fractures. The MPR framework combines a CNN for automatic feature extraction with a multi-scale generative adversarial network to model skeletal integrity using healthy samples. By leveraging healthy images to learn the normal skeletal distribution, the approach reduces the dependency on labeled fracture data and effectively addresses the challenges posed by limited pediatric datasets. Datasets from two different hospitals were used, with data augmentation techniques applied during both training and validation. On an independent test set, the proposed model achieves an accuracy of 90.5%, with 89% sensitivity, 92% specificity, and an F1 score of 0.906—outperforming the diagnostic accuracy of emergency medicine physicians and approaching that of pediatric radiologists. Furthermore, the model demonstrates a fast inference speed of 1.1 s per sheet, underscoring its substantial potential for clinical application
Bariatric metabolic surgery and cancer risk: Target trial emulation using iterative time distribution matching
Full text linkBariatric metabolic surgery (BMS) is a common intervention for severe obesity, yet its effects on cancer risk remain unclear. Observational studies and meta-analyses yield inconsistent findings, while randomized controlled trials often lack adequate follow-up to evaluate cancer outcomes. This study aims to emulate a target trial using observational data, employing a transparent and robust methodology to address this issue. We constructed a large retrospective cohort of adults with obesity in Qatar using electronic medical records from the public health system, with data available from 2018. We developed and applied iterative time distribution matching (ITDM) which is an iterative version of prescription time distribution matching (PTDM) as an improved approach to mitigate immortal time bias. This adaptation facilitated the alignment of time-zero (T0) between BMS recipients and non-recipients. Subsequently, we applied a Cox proportional hazards regression model, controlling for confounders and prognostic covariates, for data analysis. The final study cohort comprised 124,780 individuals aged 30 years and older, including 1,465 who underwent BMS and 1,583 who developed cancer during the follow-up period. The median follow-up duration was 7.79 years (IQR: 4.89–10.85). In the confounder- and prognostic covariate-adjusted Cox model, BMS was associated with a reduced hazard of cancer (HR 0.49, 95% CI 0.31 to 0.76). Given potential residual confounding and the limited outcome data, these findings provide preliminary evidence of a protective association and should be interpreted cautiously. This approach emphasizes transparency in trial emulation design, and future studies should focus on specific cancer types and long-term outcomes as additional data become available
Thrombocytopenia and neutropenia in Epstein–Barr virus infectious mononucleosis: A retrospective cohort study
Full text linkThrombocytopenia and absolute neutropenia are recognized manifestations of Epstein-Barr virus infectious mononucleosis (EBV-IM). This study conducted a retrospective analysis of laboratory results from patients clinically suspected of having EBV-IM and tested over a two-year period (2018-2019) at a single testing center in Ireland, aiming to determine the prevalence of these hematological complications. A cohort of 51 confirmed acute EBV-IM cases was established, and the incidence of thrombocytopenia and absolute neutropenia within this group was assessed. These findings were then compared to the frequencies observed in non-acute EBV-IM patients, both with and without atypical lymphocytes. Among the 51 patients diagnosed with acute EBV-IM, 14% presented with thrombocytopenia and absolute neutropenia, including instances of severe cases. A comparable prevalence of these conditions was noted in non-acute EBV-IM patients with identifiable atypical lymphocytes; however, a significantly lower incidence was found in non-acute EBV-IM patients lacking atypical lymphocytes. These results suggest that thrombocytopenia and absolute neutropenia occur in patients with viral infections and are not exclusive to acute EBV-IM
Diagnostic and prognostic value of circulating microRNA-21 in heart failure: A systematic review and meta-analysis
Full text linkHeart failure (HF) remains a leading cause of global mortality, underscoring the urgent need for reliable, minimally invasive biomarkers to facilitate early diagnosis and risk stratification. MicroRNA-21 (miR-21) has been implicated in cardiac fibrosis, hypertrophy, and the progression of HF; however, its clinical utility remains uncertain. This study presents a systematic review and diagnostic test accuracy (DTA) meta-analysis aimed at assessing the diagnostic and prognostic performance of circulating miR-21 in HF. We estimated pooled sensitivity, specificity, and area under the curve (AUC) for the DTA analysis, and synthesized hazard ratios (HRs) with 95% confidence intervals (CIs) for prognostic outcomes. Additionally, univariate meta-regression was conducted to explore demographic and clinical moderators. Our analysis included fourteen studies with a total of 1,327 participants. Results demonstrated that circulating miR-21 levels were significantly elevated in HF patients compared to controls (fold change 1.61; 95% CI 1.46–1.78; p < 0.001). The diagnostic accuracy was notably high, with a sensitivity of 0.94 (95% CI 82.0–98.0), specificity of 0.90 (95% CI 79.0–96.0), and AUC of 0.97 (95% CI 96.0–98.0). Elevated levels of miR-21 were associated with an increased risk of worsening HF severity (HR 1.84; 95% CI 1.14–2.97; p=0.01) and HF-related cardiovascular death (HR 2.00; 95% CI 1.30–3.03; p=0.001). However, no significant association was found with HF-related hospitalization (HR 0.97; 95% CI 0.61–1.52; p=0.88). Variability in sample type and differing clinical thresholds contributed to heterogeneity across studies. These findings support the potential of circulating miR-21 as a diagnostic and prognostic biomarker for HF. Nevertheless, further research with standardized sample sizes and clinical thresholds is necessary to establish robust evidence for its clinical application
Encapsulated probiotics and nanoprobiotics – Biocompatible materials, processing technologies, and applications: A review
Full text linkProbiotic efficacy is contingent upon delivering a sufficient number of viable cells to the site of action. However, industrial processing, storage, and gastrointestinal stresses frequently diminish survival rates below the ~10⁶–10⁷ CFU/g or mL typically required at the time of consumption. This review aims to provide a comprehensive overview of probiotic encapsulation—particularly micro- and nanoencapsulation—as a strategy to enhance viability and facilitate timely, site-specific release. We synthesized and analyzed existing literature on key encapsulating materials, including natural polysaccharides and proteins such as alginate, chitosan, pectin, starch, casein/whey, and selected synthetic pH-responsive polymers. We also examined major encapsulation techniques, including extrusion, emulsification, spray-drying, freeze-drying, electrospinning, and coacervation, with a focus on release mechanisms and compatibility with food matrices. Overall, encapsulation consistently improved resistance to acid, bile, oxygen, heat, and dehydration, often resulting in reduced viability losses compared to free cells, enhanced storage stability, and expanded applications in functional foods and novel biomedical delivery systems. Multilayer and nanoscale systems frequently provided additional protection and targeted release in the intestinal and colonic regions. However, performance is still dependent on specific strains and matrices, and challenges persist regarding process-induced damage, premature release, sensory and textural alterations, cost and scalability, and safety and regulatory standardization, particularly for nano-enabled formats. In conclusion, encapsulated probiotics represent a promising platform; however, future advancements should focus on the development of smart, stimuli-responsive materials, scalable automated manufacturing processes, and functional validation that extends beyond viable cell counts