Bosnian Journal of Basic Medical Sciences
Not a member yet
1870 research outputs found
Sort by
PF4 in rejuvenation therapy: Neuroprotection and cognitive enhancement
Full text linkPlatelet factor 4 (PF4), a platelet-derived chemokine found in the blood, has been identified as a critical factor in modulating the rejuvenation of the aged brain. Increasing evidence suggests that PF4 secretion is a prerequisite for the cognitive benefits associated with young blood transfusion, the longevity factor klotho, and exercise. Systemic administration of exogenous PF4 has been shown to reduce circulating pro-aging immune factors and restore peripheral immune function in the aged brain by mitigating age-related hippocampal neuroinflammation, promoting molecular changes in synaptic plasticity, and improving cognitive function in aged mice. Clinically, reduced serum PF4 levels have been significantly associated with cognitive decline and core pathological biomarkers in Alzheimer’s disease. Mechanistically, the chemokine receptor CXCR3 partially mediates the cellular, molecular, and cognitive benefits of systemic PF4 administration in the aged brain. However, several critical questions remain, including the potential role of PF4 in blood–brain communication, its interaction with neurotransmitters and neuropharmacological processes, and how these findings might be translated into clinical practice. Further detailed studies are needed to validate and expand upon these insights for therapeutic application
Identification and validation of TUBB, CLTA, and FBXL5 as potential diagnostic markers of postmenopausal osteoporosis
Full text linkPostmenopausal osteoporosis (PMOP) is recognized as the most prevalent bone disease worldwide. N6-methyladenosine (m6A) is one of the most common RNA modifications influencing the progression of various disorders; however, its specific role in PMOP remains unexplored. This study aims to investigate the expression profiles of m6A-related genes and their impact on the prognosis of PMOP patients. We utilized the GSE56815 expression analysis dataset obtained from the Gene Expression Omnibus (GEO) database and extracted m6A-related genes for further examination. Our analysis revealed that m6A-related genes exhibited differential expression between PMOP patients and healthy controls. We employed consensus clustering to identify subgroups within the PMOP cohort and conducted immunological analyses on these clusters. Additionally, we intersected the clusters to identify differentially expressed genes (DEGs) and analyzed potential diagnostic markers for PMOP using support vector machine recursive feature elimination (SVM-RFE), LASSO, and random forest (RF) algorithms, which were subsequently validated in the GSE56116 dataset. The receiver operating characteristic (ROC) curve was employed to assess the diagnostic significance of these markers. Furthermore, quantitative PCR (qPCR) was performed to validate the expression of the identified genes. In the GSE56815 dataset, we identified three subtypes associated with m6A modifications, leading to the identification of 302 shared DEGs among these subtypes. Gene ontology (GO) analysis indicated that the DEGs were predominantly enriched in nuclear specks, the nuclear envelope, and nucleocytoplasmic transport processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis further revealed that DEGs were primarily associated with endocytosis and nucleocytoplasmic transport pathways. Through the application of SVM, LASSO, and RF algorithms, we identified three potential diagnostic markers: TUBB, CLTA, and FBXL5, which demonstrated promising diagnostic capabilities when tested against an independent dataset. qPCR validation confirmed significant expression differences of these genes between the control and PMOP groups. The genetic markers identified in this study hold potential for accurately predicting the risk of PMOP in patients. The findings contribute to understanding the underlying molecular mechanisms of CLTA, TUBB, and FBXL5 in PMOP and may facilitate the development of novel therapeutic strategies and improved monitoring of the disease
Immunogenic cell death-related risk signature for tumor microenvironment profiling and prognostic prediction in colorectal cancer
Full text linkImmunogenic cell death (ICD) reshapes the tumor immune microenvironment and activates the adaptive immune response. However, the clinical significance of ICD-associated genes in colorectal cancer (CRC) remains unclear. In this study, we used weighted gene co-expression network analysis (WGCNA) to identify ICD-related gene modules. An ICD-related risk score (ICDRS) was then constructed using Cox regression modeling and LASSO analysis. Immune cell infiltration in patients with different risk levels was assessed using the ESTIMATE and single-sample Gene Set Enrichment Analysis algorithms (GSEA). The oncoPredict package was employed to explore the association between the ICDRS and chemotherapy drug sensitivity. Finally, the expression levels of ICD-related genes were validated through in vitro cellular experiments. Three CRC prognostic genes—CLMP, Neuropilin-1 (NRP1), and PLEKHO1—were identified from a set of 34 ICD-associated genes based on WGCNA and LASSO analyses. These genes were used to construct the ICDRS model. Notably, a high ICDRS was found to be an independent predictor of poorer overall survival (OS) in CRC patients. High-risk patients also exhibited increased immune cell infiltration. Moreover, the ICDRS was significantly correlated with sensitivity to conventional chemotherapeutic drugs, suggesting its potential utility in guiding personalized chemotherapy. Cellular assays confirmed that CLMP, NRP1, and PLEKHO1 were differentially expressed between normal and cancerous cells, and that NRP1 specifically promoted the proliferation, migration, and invasion of CRC cells. In conclusion, the ICDRS may serve as a reliable predictor of CRC prognosis and offers a promising direction for the clinical management of CRC patients
Metagenomic and metabolomic analysis of gut microbiome\u27s role in spinal cord injury recovery in rats
Full text linkSpinal cord injury (SCI) induces profound systemic changes, including disruptions in gut microbiome composition and host metabolism. This study aimed to investigate the impact of SCI on gut microbial diversity and serum metabolites in rats, and to explore potential microbiome–metabolite interactions that may influence recovery. Male Sprague–Dawley (SD) rats were assigned to either SCI or sham-operated groups. Fecal samples were collected for whole-genome metagenomic sequencing, and serum samples were analyzed using untargeted metabolomics. Gut microbial composition and diversity were assessed using α- and β-diversity indices, while Linear discriminant analysis effect size (LEfSe) identified differentially abundant taxa. Metabolomic pathway analysis was performed to detect significant changes in serum metabolites, and Spearman’s correlation was used to evaluate associations between gut microbes and metabolites. SCI significantly altered gut microbiota composition, with increased proportions of Ligilactobacillus and Staphylococcus, and decreased proportions of Lactobacillus and Limosilactobacillus. Metabolomic analysis revealed disrupted energy metabolism and elevated oxidative stress in SCI rats, as indicated by increased serum levels of pyruvate and lactic acid. Correlation analysis further identified significant associations between specific gut bacteria and key metabolites, suggesting microbiome-driven metabolic dysregulation following SCI. These findings highlight significant interactions between the gut microbiota and host metabolism after SCI and suggest that microbiome-targeted interventions may hold therapeutic potential for improving recovery by modulating metabolic function and oxidative stress responses
OncoImmune machine-learning model predicts immune response and prognosis in leiomyosarcoma
Full text linkLeiomyosarcoma (LMS) is one of the most aggressive tumors originating from smooth muscle cells, characterized by a high recurrence rate and frequent distant metastasis. Despite advancements in targeted therapies and immunotherapies, these interventions have failed to significantly improve the long-term prognosis for LMS patients. Here, we identified OncoImmune differential expressed genes (DEGs) that influence monocytes differentiation and the progression of LMS, revealing varied immune activation states of LMS patients. Using a machine learning approach, we developed a prognostic model based on OncoImmune hub DEGs, which offers a moderate accuracy in predicting risk levels among LMS patients. Mechanistically, we found that ATRX mutation may regulate coiled-coil domain-containing protein 69 (CCDC69) expression, leading to functional alterations in mast cells and immune unresponsiveness through the modulation of various immune-related signaling pathways. This machine learning-based prognostic model, centered on seven OncoImmune hub DEGs, along with ATRX gene status, represents promising biomarkers for predicting prognosis, molecular characteristics, and immune features in LMS
Global, regional, and national trends in thyroid cancer burden (1990–2021): Insights from the GBD 2021 study
Full text linkThe global incidence of thyroid cancer (TC) has been steadily increasing and is now recognized as one of the most prevalent endocrine malignancies. This study provides a comprehensive evaluation of the prevalence, incidence, mortality, and disability-adjusted life years (DALYs) associated with TC from 1990 to 2021. Data for this study were sourced from the 2021 Global Burden of Disease, Injuries, and Risk Factors Study (GBD). To quantify temporal patterns and assess trends in age-standardized TC metrics—namely, age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and DALYs—estimated annual percentage changes (EAPCs) were calculated. The analysis was stratified by sex, 20 age groups, 21 GBD regions, 204 countries/territories, and five Socio-demographic Index (SDI) quintiles. Statistical analyses and plotting were conducted using R statistical software version 4.4.2 and Joinpoint software. The study found that the global burden of thyroid cancer remains substantial, with a significant increase in the total number of cases. In 2021, regions with high SDI reported the highest ASPR, showing an upward trend compared to 1990; however, this trend began to decline significantly after 2009. Conversely, regions with low and low-middle SDI exhibited noticeable increases in ASPR, ASIR, ASDR, and DALYs. The highest prevalence and incidence were observed in the 55-59 age group, followed by a gradual decline. The majority of affected individuals were women. A high body mass index (BMI) was identified as the primary risk factor for TC, and both prevalence and incidence are expected to continue rising through 2040
Melatonin and omega-3 neuroprotection in prenatal rat spinal cord exposed to 900 MHz electromagnetic field
Full text linkThe electromagnetic field (EMF) emitted by electronic devices induces pathological changes in tissues, adversely affecting embryonic and pubertal development. This study investigates the effects of melatonin (Mel) and omega-3 fatty acids (ω3) on the spinal cord in rats exposed to EMF, employing stereological methods alongside light and electron microscopic evaluations. Pregnant Wistar albino rats were divided into seven groups: Control (CONT), sham-exposed (SHAM), EMF alone, EMF-Mel, EMF-ω3, Mel only, and ω3 only. The EMF, EMF-Mel, and EMF-ω3 groups were exposed to a 900 MHz EMF for two hours daily during the prenatal period (21 days). Mel and ω3 were administered via intragastric gavage prior to EMF exposure. Upon completion of the experiment (on the 35th day post-birth), spinal cord tissues of all male offspring were dissected and subjected to light and ultrastructural examinations. Stereological analyses calculated grey matter (GM) to total volume ratios, white matter (WM) to total volume ratios, GM to WM volume ratios, total spinal cord volume, and motor neuron counts. No significant differences were observed among the groups regarding GM/WM volume ratios, GM/total volume ratios, WM/total volume ratios, and total spinal cord volume (p > 0.05). However, a significant reduction in motor neuron numbers was noted in the EMF-ω3 group compared to the CONT group (p < 0.01). Light and ultrastructural examinations revealed marked motor neuron degeneration and axonal disruption in the EMF group, which were mitigated in the Mel and ω3-treated groups. These findings indicate that prenatal exposure to 900 MHz EMF exerts detrimental effects on spinal cord tissue and underscore the necessity for further studies exploring varying doses and durations to elucidate the potential effects of ω3 and Mel
Extraovarian fibrothecomas: Two case reports and comprehensive review of ovarian sex cord-stromal fibroma-thecoma tumors
Full text linkSex cord-stromal tumors are rare ovarian neoplasms, with fibromas comprising approximately 4% and thecomas accounting for 0.5–1% of all ovarian tumors. The occurrence of these tumors outside the ovaries is exceptionally rare and diagnostically challenging, often mimicking malignancy when associated with ascites, elevated CA-125 levels, or Meigs-like syndrome. This review aims to synthesize current knowledge on the histopathological, immunohistochemical, radiological, and molecular features of ovarian fibroma-thecoma group tumors and highlight their clinical relevance. We report two postmenopausal women with large abdominal masses located extraovarian: one in the broad ligament and the other adherent to the omentum and intestines. In the first case, markedly elevated CA-125, ascites, and pleural effusion initially suggested Meigs syndrome. The second case presented with an abdominal mass and ascites. Imaging studies indicated the possibility of malignant ovarian tumors in both patients, leading to surgical excision. Histopathological examination revealed spindle-to-oval tumor cells arranged in fascicular or storiform patterns, with focal lipid-rich theca-like cells. Immunohistochemical analysis showed that the tumors were positive for vimentin, WT1, progesterone receptor (PR), and variably for estrogen receptor (ER), CD56, inhibin, and calretinin, while being negative for markers of epithelial, melanocytic, and gastrointestinal stromal tumors. A review of the literature identified only 11 well-documented cases of extraovarian fibroma-thecoma group tumors, which most commonly arise in the broad ligament or pelvic cavity. These cases are frequently associated with ascites and elevated CA-125 levels and are often misdiagnosed preoperatively as malignant disease. Our cases underscore the importance of considering extraovarian fibromas and thecomas in the differential diagnosis of pelvic and abdominal masses presenting with similar features. Accurate pathological assessment can prevent unnecessary radical surgeries and promote more favorable patient outcomes.
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
Differential effects of apelin-13 on lipid peroxidation and DNA oxidation in doxorubicin-treated rats: A preliminary study
Full text linkDoxorubicin-induced cardiotoxicity is closely associated with oxidative stress (OS), and apelin-13 has been proposed as a potential cardioprotective peptide. However, its effects on specific oxidative stress (OS) markers remain poorly understood. This preliminary study aimed to evaluate the impact of apelin-13 on oxidative stress markers in rats chronically treated with doxorubicin (DOX). Male rats received DOX with or without apelin-13 (40 µg/kg body weight/day). The levels of 8-hydroxy-2\u27-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) were measured as indicators of oxidative DNA damage and lipid peroxidation, respectively. The DOX treatment resulted in increased MDA levels, which were unaffected by apelin-13. Conversely, 8-OHdG levels decreased with DOX alone but returned to baseline levels in the presence of DOX and apelin-13. In conclusion, while apelin-13 did not mitigate DOX-induced lipid oxidative damage, it may selectively influence nuclear OS markers. This suggests a complex and context-dependent role of apelin-13 in modulating oxidative stress associated with DOX treatment