Bosnian Journal of Basic Medical Sciences
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Influence of menopause status on T-helper cell profiles in acute myocardial infarction
Full text linkEstrogens modulate immune responses, particularly the activation and polarization of CD4+ T cells, which play key roles in cardiovascular homeostasis. This proof-of-concept study investigated the effect of menopausal status on the polarization of T-helper (Th) cells in women with acute myocardial infarction (AMI). A total of 41 female AMI patients were enrolled—seven premenopausal and 34 postmenopausal—and compared with a group of 17 male AMI patients. Flow cytometry was used to evaluate CD4+ T-cell subsets, including Th1 (T-bet+), Th2 (GATA3+), and Th17 (RORγt+) phenotypes. Serum levels of representative cytokines were also measured. Women exhibited higher numbers of circulating CD4+ T cells compared to men, with a marked shift toward the Th1 phenotype. Postmenopausal women demonstrated increased cardiovascular risk, as indicated by higher QRISK3 and GRACE scores, as well as elevated levels of C-reactive protein and cardiac troponin T compared to premenopausal women. However, menopausal status had minimal impact on Th cell polarization, as no significant differences were observed in the proportions of Th1, Th2, or Th17 subsets between premenopausal and postmenopausal women. Similarly, levels of interleukin (IL)-6, IL-1β, IL-10, tumor necrosis factor, and monocyte chemoattractant protein-1 were comparable between the two groups. This proof-of-concept study highlights sex-specific differences in immune responses and inflammatory profiles during AMI. Women exhibited a stronger polarization toward the Th1 phenotype, along with elevated markers of inflammation and myocardial injury. Notably, menopausal status did not significantly affect lymphocyte subpopulations or circulating cytokine levels
Vitamin D supplementation for tuberculosis prevention: A meta-analysis
Full text linkVitamin D plays an important role in immune regulation, prompting interest in its potential for preventing tuberculosis. However, clinical findings regarding its protective effects against tuberculosis infection and disease remain inconsistent. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the impact of vitamin D supplementation on the prevention of tuberculosis infection and the progression to active tuberculosis. We searched PubMed, Embase, Cochrane Library, and Web of Science databases through January 2025. Eligible studies involved participants without active tuberculosis at baseline and reported outcomes related to tuberculosis. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup and sensitivity analyses were conducted, and the certainty of evidence was evaluated using the GRADE approach. Six RCTs, involving 15,677 participants, met our inclusion criteria. Compared to placebo, vitamin D supplementation did not significantly reduce the risk of tuberculosis infection (5 RCTs; OR: 0.95; 95% CI: 0.79–1.14; p = 0.55) or the development of active tuberculosis (4 RCTs; OR: 0.77; 95% CI: 0.56–1.05; p = 0.10). The certainty of evidence was moderate for both outcomes. Subgroup analyses based on baseline vitamin D levels and duration of follow-up yielded consistent results. The incidence of serious adverse events was comparable between the vitamin D and placebo groups (OR: 1.02; 95% CI: 0.76–1.38; p = 0.87), and none of the serious events were attributed to vitamin D supplementation. In conclusion, vitamin D supplementation does not significantly reduce the risk of tuberculosis infection or progression to active tuberculosis, although it is safe and well tolerated
Integrins and pulmonary fibrosis: Pathogenic roles and therapeutic opportunities
Full text linkCharacterized by the formation of fibrotic scars, pulmonary fibrosis (PF) involves a complex pathogenesis, limited treatment options, and a high mortality rate. Integrins—heterodimeric transmembrane proteins composed of α and β subunits—mediate extracellular matrix remodeling and regulate the physiological functions of epithelial, mesenchymal, and immune cells through "inside-out" and "outside-in" signaling pathways. These molecules play a critical role in the initiation and progression of PF. Due to their central regulatory functions, a range of integrin-targeted therapies has been developed. However, the complex pathophysiology of PF and the structural diversity of integrins pose significant challenges to targeted treatment. In this study, we systematically delineated the signaling networks mediated by the full spectrum of integrin family members and uncovered the molecular mechanisms by which they contribute to PF through immunoregulatory pathways. We also reviewed the development of integrin-based therapies from preclinical studies to clinical trials and discussed current priorities in clinical, basic, and translational research. These insights may provide new perspectives for the diagnosis and treatment of PF.
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.
Serum NPTX2 and cognitive impairment in geriatric diabetes
Full text linkCognitive impairment is an increasingly common complication of diabetes, yet its underlying pathophysiological mechanisms remain poorly understood. Neuronal pentraxin 2 (NPTX2), a recently identified synaptic biomarker linked to cognitive disorders, has not previously been examined in relation to cognitive function in geriatric individuals with diabetes. This cross-sectional study enrolled 90 participants—46 geriatric patients with diabetes and 44 age-matched non-diabetic controls. Demographic and clinical data were collected for all participants. After informed consent, cognitive function was assessed with the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). Serum NPTX2 levels were measured by ELISA. No significant differences were found between the diabetic and control groups in age, sex, education level, marital status, smoking history, comorbid conditions, or polypharmacy. However, the groups differed significantly in MoCA scores (p < 0.001), MMSE scores (p = 0.028), and NPTX2 levels (p = 0.048); the diabetic group showed lower cognitive scores and biomarker levels. NPTX2 levels correlated positively with MoCA and MMSE scores and negatively with diabetes duration, patient age, and the presence of microvascular complications. In conclusion, cognitive function was significantly lower in geriatric patients with diabetes than in controls, and serum NPTX2 levels were significantly associated with cognitive performance. These findings suggest a possible role for NPTX2 in diabetes-related cognitive decline and support further investigation of its utility within a broader biomarker panel
Sugammadex vs neostigmine in post-anesthesia recovery: A systematic review and meta-analysis
Full text linkResidual neuromuscular blockade (RNB) is linked to an increased risk of perioperative adverse events. This study systematically evaluates the impact of neuromuscular blockade antagonists on postoperative complications and quality of recovery in surgical patients. We conducted a systematic review and meta-analysis to compare the efficacy of sugammadex and neostigmine. Comprehensive searches were performed across medical databases, including Web of Science, PubMed, Embase, and the Cochrane Library, with a final search date of April 6, 2025. A total of thirty-five randomized controlled trials (RCTs) involving 4,275 patients, along with two retrospective studies comprising 49,642 participants, met the inclusion criteria. The meta-analysis revealed that sugammadex facilitated faster reversal of RNB compared to neostigmine, as indicated by a quicker recovery to a train-of-four ratio (TOFR) ≥ 0.9 (standardized mean difference [SMD] -3.45; 95% confidence interval [CI], -4.42 to -2.48), a shorter extubation time (SMD -1.44; 95% CI, -2.02 to -0.85), and a decreased incidence of RNB (risk ratio [RR] 0.18; 95% CI, 0.07 to 0.47). Moreover, sugammadex significantly reduced postoperative complications compared to neostigmine, including the incidence of postoperative nausea and vomiting (PONV) (RR 0.64; 95% CI, 0.46 to 0.88), postoperative pulmonary complications (PPCs) (RR 0.62; 95% CI, 0.38 to 0.99), and bradycardia (RR 0.32; 95% CI, 0.20 to 0.50). In conclusion, sugammadex provides a faster reversal of neuromuscular blockade compared to neostigmine and is associated with a reduction in postoperative complications. However, this expedited reversal does not result in measurable improvements in overall recovery quality, nor do either sugammadex or neostigmine significantly affect postoperative cognitive function
Ending nuclear weapons, before they end us
Full text linkThis May, the World Health Assembly (WHA) will vote on re-establishing a mandate for the World Health Organization (WHO) to address the health consequences of nuclear weapons and war (1). Health professionals and their associations should urge their governments to support such a mandate and support the new UN comprehensive study on the effects of nuclear war.
Read more in the PDF https://www.bjbms.org/ojs/index.php/bjbms/article/view/12736/3911
Neoadjuvant stereotactic radiosurgery for brain metastases: Current evidence and clinical perspectives
Full text linkNeoadjuvant stereotactic radiosurgery (SRS) has emerged as a promising strategy for managing brain metastases, offering several advantages over traditional postoperative approaches. By delivering targeted radiation prior to surgical resection, neoadjuvant SRS aims to enhance local tumor control, reduce the risk of leptomeningeal dissemination, and optimize treatment efficiency. Recent findings suggest that neoadjuvant SRS provides comparable, if not superior, local control compared to postoperative SRS, while exhibiting lower rates of radiation necrosis and leptomeningeal disease. However, uncertainties persist regarding optimal dosing regimens, treatment timing, and patient selection criteria, as factors such as tumor size, volume, and histology may significantly influence clinical outcomes. Additionally, while neoadjuvant SRS addresses challenges related to target delineation and delays associated with postoperative treatment, its long-term efficacy and integration with systemic therapies require further investigation. This review consolidates evidence from recent retrospective and prospective studies, focusing on key outcomes such as local control rates, radiation toxicity profiles, and overall survival
Ivermectin attenuates nicotine-induced reward-like behaviors in mice
Full text linkNicotine addiction poses a significant public health threat, particularly within the realm of emergency medicine, where it is associated with serious complications, including cardiovascular events and respiratory distress. The limited effectiveness of current pharmacological treatments for nicotine dependence underscores the urgent need for innovative and effective therapeutic approaches. Recent studies have shown that ivermectin, an antiparasitic agent, modulates the GABAergic, glutamatergic, and purinergic systems, which are implicated in the pathophysiology of addiction. This study aimed to examine the effects of ivermectin on the acquisition, extinction, and reinstatement of nicotine dependence in mice, utilizing the conditioned place preference (CPP) test, a widely recognized methodology in drug addiction research. Ivermectin (1 and 5 mg/kg, i.p.) was co-administered with nicotine (0.5 mg/kg, i.p.) over three consecutive days during the acquisition phase of nicotine dependence. In a separate experiment, the influence of ivermectin on the reinstatement of nicotine-induced CPP was assessed following an extinction period, using a single nicotine priming injection (0.1 mg/kg). Results indicated that ivermectin (1 and 5 mg/kg) significantly reduced the development of nicotine dependence (p < 0.05). Furthermore, ivermectin (5 mg/kg) facilitated the extinction of nicotine-induced CPP (p < 0.01) and attenuated the reinstatement of nicotine-induced CPP triggered by a priming dose of nicotine (p < 0.01). In contrast, administration of the lower dose of ivermectin (1 mg/kg) did not yield statistically significant effects on either the extinction or reinstatement phases (p > 0.05). Additionally, nicotine administration, alone or in combination with ivermectin at the tested doses, did not produce significant changes in motor coordination or locomotor activity. These findings suggest that ivermectin may attenuate both the acquisition and reinstatement of nicotine-induced CPP while facilitating the extinction of nicotine dependence. Collectively, the results indicate that ivermectin holds potential as a therapeutic agent in the treatment of nicotine addiction
Arbutin as a potential nephroprotective agent: Dose-related effects in renal ischemia-reperfusion injury
Full text linkIschemia-reperfusion injury (IRI) presents a complex pathophysiology characterized by oxidative stress and inflammation. Arbutin, widely recognized for its use in skin whitening, also exhibits antioxidant, anti-inflammatory, and anticancer properties. This study aimed to assess the potential protective effects of arbutin at two different doses against IRI in the kidneys. Twenty-four male Wistar albino rats were randomly assigned to four equal groups: Control, IRI, 250 mg/kg arbutin + IRI (AR250+IRI), and 1000 mg/kg arbutin + IRI (AR1000+IRI). Arbutin was administered orally via gavage for 14 days to ensure sub-acute application. Following left kidney nephrectomy, ischemia was induced in the right kidney using a non-traumatic clamp for 45 minutes, succeeded by 60 minutes of reperfusion. Blood and tissue samples were subsequently collected for analysis. In the IRI group, levels of malondialdehyde, myeloperoxidase, interleukin-1 beta, and creatinine were significantly elevated; these levels decreased in the groups receiving arbutin supplementation. Notably, ischemia-modified albumin, urea, superoxide dismutase (inhibition ratio), and tumor necrosis factor alpha levels were reduced in the AR1000+IRI group. Additionally, decreased levels of catalase and glutathione peroxidase were observed in the AR1000+IRI group. Histopathological examination revealed flattening, necrosis, degeneration, dilation, glomerular necrosis, sclerosis, Bowman capsule dilation, and interstitial hemorrhage in the IRI group. The AR250+IRI group exhibited mild cortical-medullary congestion and a slight increase in glomerular size. Conversely, the AR1000+IRI group displayed a histological appearance resembling that of the control group. In conclusion, arbutin demonstrates potential protective effects against IRI. Its use may be recommended prophylactically for individuals at risk of developing IRI