Bosnian Journal of Basic Medical Sciences
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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
Prognostic impact of sleep-disordered breathing on mortality and cardiovascular events in renal dialysis: A meta-analysis
Full text linkSleep-disordered breathing (SDB) is prevalent among patients undergoing renal dialysis, yet its prognostic implications for mortality and cardiovascular outcomes remain unclear. This meta-analysis investigates the relationship between SDB and all-cause mortality as well as major adverse cardiovascular events (MACEs) within this demographic. A systematic search of PubMed, Embase, and Web of Science was conducted from inception to May 29, 2025, focusing on longitudinal observational studies that assessed SDB in adult dialysis patients. The primary outcome analyzed was all-cause mortality, while the secondary outcome was MACEs. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using random-effects models to account for heterogeneity. A total of eleven cohort studies encompassing 656,328 dialysis patients, of which 23,725 had SDB, were included. The results indicated that SDB was significantly associated with an increased risk of all-cause mortality (HR: 1.79, 95% CI: 1.42–2.25; I² = 32%; p < 0.001). Notably, the association was more pronounced in Asian studies (HR: 2.07) compared to non-Asian studies (HR: 1.35; p for subgroup difference = 0.008) and in studies employing polysomnography or pulse oximetry versus those using ICD codes (HR: 2.57 and 2.00 vs. 1.35; p = 0.002). Furthermore, five studies indicated that SDB was linked to an elevated risk of MACEs (HR: 2.68, 95% CI: 1.86–3.85; I² = 0%; p < 0.001). In conclusion, SDB is associated with heightened mortality and cardiovascular risk in patients on renal dialysis. These findings underscore the necessity for increased awareness and management of SDB in this population. However, further interventional studies are required to ascertain whether systematic screening and treatment can enhance clinical outcomes
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
Acid ceramidase expression and biomarker potential in patients with locally advanced rectal cancer
Full text linkAcid ceramidase (AC), a pivotal enzyme in sphingolipid metabolism, has been associated with various cancers; however, its specific role in rectal cancer remains poorly understood. This study aimed to explore the clinical significance of AC gene and protein expression in rectal cancer. We analyzed the expression of ASAH1, BAX, and BCL2 through quantitative Real-Time PCR in paired tumor and non-tumor tissue samples obtained from patients with locally advanced rectal cancer (LARC) prior to neoadjuvant chemoradiotherapy. Additionally, serum AC levels and standard biochemical parameters were assessed. We further evaluated ASAH1 expression using RNA-seq data from publicly available TCGA-READ datasets accessed via the UCSC Xena Browser. Two approaches indicated a significant reduction in ASAH1 expression in tumor tissue (p=0.004 and p<0.001, respectively). Receiver operating characteristic curve analysis revealed a modest capacity for ASAH1 expression to differentiate between tumor and non-tumor tissue in LARC patients (AUC=0.652, p=0.042). No correlation was observed between ASAH1 expression and the BAX/BCL2 ratio in tumor tissue, nor with serum AC levels or the CRP-albumin-lymphocyte (CALLY) index. Conversely, serum AC levels exhibited a negative correlation with the BAX/BCL2 ratio (rs=−0.536, p=0.002, FDR-adjusted q=0.021). Furthermore, ASAH1 expression, AC levels, and the CALLY index were not linked to overall survival or treatment response. A key finding of this study is the inverse relationship between serum AC levels and the pro-apoptotic status of tumor tissue, suggesting that circulating AC may provide valuable insights into tumor apoptotic activity. Further large-scale studies are necessary to validate these preliminary findings and elucidate the biomarker potential of AC in rectal cancer
The molecular mechanisms of cuproptosis and its relevance to atherosclerosis
Full text linkAtherosclerosis (AS) is a chronic inflammatory disease associated with lipid deposition in the vascular intima. Copper is a vital trace element implicated in the onset and progression of AS. Excessive intracellular copper accumulation induces a unique form of cell death termed “cuproptosis.” The emergence of the concept of cuproptosis has highlighted the potential role of copper in AS. This review explores the regulatory mechanisms of copper metabolism and cuproptosis, summarizes recent findings on the link between copper excess and AS, and examines how cuproptosis may influence AS progression. The goal is to propose novel diagnostic and therapeutic strategies for AS through the lens of cuproptosis
Drug-coated balloon treatment for tasc c/d infrapopliteal disease: Two-year matched cohort outcomes
Full text linkAs the most common form of peripheral arterial disease, lower extremity arterial disease—caused by atherosclerotic stenosis or occlusion—has led to widespread concern due to the high risk of postoperative restenosis. This study aimed to evaluate the effectiveness of drug-coated balloon (DCB) angioplasty in treating severe infrapopliteal artery (IPA) lesions. Plain old balloon (POB) angioplasty served as the control. Patients who underwent procedures at our center for Trans-Atlantic Inter-Society Consensus (TASC) C/D IPA lesions between June 2020 and June 2022 and met the inclusion criteria were enrolled in this retrospective cohort study, which used the propensity score matching (PSM) method. The primary outcomes were the 2-year cumulative rates and survival trends of primary patency (PP) and target lesion revascularization (TLR), based on the treated lesions. Secondary outcomes included limb-based major amputation (MA) and patient-based all-cause death (ACD). A total of 278 target lesions were initially included, with significant differences (p < 0.05) observed in some non-outcome variables. After PSM, analyses were conducted on 240 target lesions, 221 limbs, and 195 patients. The PSM models satisfied both the common support and parallel trend assumptions. In terms of PP, the 2-year cumulative rate in the DCB group was significantly higher than in the POB group (48.0% vs. 22.9%, p < 0.001). The log-rank test yielded a p-value of &lt; 0.001, and the adjusted hazard ratio (HR) from Cox regression analysis was 2.303 [95% confidence interval (CI): 1.518–3.495]. However, there was no statistically significant difference in TLR between the two groups: the 2-year cumulative rates were 25.0% vs. 27.1% (p = 0.767), the log-rank test p-value was 0.563, and the adjusted HR was 0.956 (95% CI: 0.523–1.747). Similarly, no significant differences were found between groups in MA or ACD (p > 0.05). Based on these findings, the study concludes that for severe IPA lesions such as TASC C/D, DCB angioplasty is superior to POB angioplasty in maintaining primary patency over a 2-year period, without any inferiority in other clinical outcomes
Retraction: Tocilizumab inhibits neuronal cell apoptosis and activates STAT3 in cerebral infarction rat model
Full text linkRetracted article: https://www.bjbms.org/ojs/index.php/bjbms/article/view/853
Following publication, concerns were raised by readers and the public regarding the integrity of the data presented in two figures of this article:
Figure 2B: An unexpected overlap was found between an image presented in this study and figures published in other articles.Figure 4: An unexpected overlap was detected within the Western blot panels, suggesting potential duplication or manipulation.
The editorial office contacted all authors on 13 January 2025 and 30 January 2025 to clarify these concerns. On 4 March 2025, the corresponding author was specifically approached through both the e-mail address provided upon article submission and an institutional e-mail located online. However, no response or explanation was ever received.
Following our journal’s policies and guidelines from the Committee on Publication Ethics (COPE), the editors have decided to retract the article from publication due to serious concerns about the reliability and originality of the data. This retraction is intended to maintain the integrity of the scientific record.
We apologize to the readership for any inconvenience caused. We thank the individuals who brought these concerns to our attention.
The Editor-in-Chief has approved this retraction note
The role of genome-wide DNA methylation and polymorphisms in periodontitis etiology: A narrative review
Full text linkPeriodontitis is a multifactorial inflammatory disease influenced by genetic, epigenetic, and environmental factors. Recent advancements in genomic and epigenomic research have highlighted the role of genetic polymorphisms and genome-wide DNA methylation in its pathogenesis. DNA methylation regulates gene expression, affecting immune responses and inflammatory pathways, while genetic polymorphisms may predispose individuals to altered host-microbial interactions and increased susceptibility to periodontal destruction. Recent studies have identified promising periodontal biomarkers, including specific genetic and epigenetic markers, that may aid in early diagnosis, risk assessment, and monitoring of disease progression. This narrative review synthesizes current evidence on the genetic and epigenetic mechanisms involved in the etiology of periodontitis, with a focus on genome-wide DNA methylation and genetic polymorphisms. It also explores their potential implications for disease pathogenesis, diagnostics, and therapeutic strategies. Future research directions include integrative multi-omics approaches to better understand the complex interplay between genetic, epigenetic, and environmental factors. Such efforts aim to support the development of personalized therapeutic strategies. Overall, this review underscores the critical role of genetic and epigenetic mechanisms in the pathogenesis of periodontitis and emphasizes the need to translate these findings into clinical practice through molecular diagnostics and personalized treatment approaches
Influence of intravenous iron therapy on mortality and cardiovascular events of patients on hemodialysis: A meta-analysis
Full text linkIntravenous (IV) iron is widely utilized to manage anemia in patients undergoing maintenance hemodialysis; however, its long-term safety remains uncertain. This meta-analysis aimed to evaluate the impact of IV iron on all-cause mortality and major adverse cardiovascular events (MACEs) within this population. We conducted a systematic search of PubMed, Embase, Cochrane Library, Web of Science, Wanfang, and CNKI up to March 2025 for randomized controlled trials (RCTs) that compared IV iron with placebo/usual care, oral iron, or varying doses of IV iron in adult hemodialysis patients. The primary outcomes assessed were all-cause mortality and MACEs. Data were synthesized using a random-effects model, and the quality of evidence was evaluated employing the GRADE approach. A total of fifteen RCTs involving 4,257 patients were included in the analysis. Compared to placebo/usual care, IV iron did not significantly affect all-cause mortality (OR: 1.36; 95% CI: 0.60–3.09) or MACEs (OR: 0.81; 95% CI: 0.43–1.55), with a moderate level of evidence. Furthermore, IV iron demonstrated no significant differences in mortality (OR: 0.58; 95% CI: 0.18–1.90) or MACEs (OR: 2.47; 95% CI: 0.37–16.34) when compared to oral iron, although the quality of evidence in this comparison was very low. High-dose IV iron was associated with a reduced mortality rate compared to low-dose IV iron (OR: 0.81; 95% CI: 0.67–0.97), though this result was influenced by a single large study. In conclusion, IV iron does not appear to increase mortality or MACEs relative to placebo or oral iron. While high-dose IV iron may decrease mortality, the evidence remains limited, indicating a need for further research
Function and mechanism of miRNAs during the process of Klebsiella pneumoniae infection: A review
Full text linkKlebsiella pneumoniae (K. pneumoniae), a Gram-negative bacterium, is a major cause of nosocomial infections and can lead to severe, widespread infections. The rise of hypervirulent and multidrug-resistant K. pneumoniae presents significant challenges to public health. Diseases associated with K. pneumoniae, such as pneumonia, lung injury, peritonitis, and sepsis, have garnered increasing attention. MicroRNAs (miRNAs) are a class of short, endogenously expressed non-coding RNAs that regulate gene expression by inhibiting translation or promoting mRNA degradation. As key regulators of gene expression, miRNAs play a crucial role in K. pneumoniae infections by modulating host inflammatory pathways, suppressing inflammasome activity, regulating cytokine secretion, and facilitating post-translational modifications. Understanding miRNA alterations and their mechanisms during K. pneumoniae infections is of great significance. This comprehensive review explores the functions and mechanisms of miRNAs in K. pneumoniae-induced lung injury, peritonitis, and sepsis. By analyzing differential miRNA expression during infection, we aim to provide new insights and potential directions for future clinical diagnosis and treatment strategies for K. pneumoniae infections