Bosnian Journal of Basic Medical Sciences
Not a member yet
1870 research outputs found
Sort by
LncRNA interactomes and co-methylation in breast cancer regulation
Full text linkBreast cancer is the most commonly diagnosed malignancy in women. Despite advances in diagnostics and treatment, the key molecular mechanisms underlying its development remain incompletely understood. This study aimed to identify novel lncRNA–miRNA–mRNA regulatory networks potentially involved in breast cancer–associated signaling pathways. Using an RT² lncRNA PCR Array and bioinformatic analysis, we identified seven differentially expressed (DE) lncRNAs. Four of these—ADAMTS9-AS2, HAND2-AS1, HOTAIRM1, and MEG3—were prioritized through integrative evaluation. qPCR confirmed their downregulation and aberrant methylation in breast tumor samples. We observed significant positive expression correlations between the pairs ADAMTS9-AS2–MEG3, HAND2-AS1–MEG3, and HOTAIRM1–MEG3, as well as co-methylation among ADAMTS9-AS2–HAND2-AS1, ADAMTS9-AS2–HOTAIRM1, HAND2-AS1–MEG3, and HAND2-AS1–HOTAIRM1, suggesting coordinated regulation. These findings are consistent with data from GEPIA 2.0. Bioinformatic prediction identified TCF7L2 as a common target gene of these lncRNAs, which is involved in the Wnt, Hippo, and MAPK signaling pathways. We also identified several miRNAs interacting with ADAMTS9-AS2. In a cohort of 50 tumor samples, we confirmed inverse associations between ADAMTS9-AS2 expression and levels of miR-106a-5p (rs = –0.46, p = 0.03) and miR-17-5p (rs = –0.41, p = 0.04). Collectively, these findings reveal novel co-regulated lncRNA–miRNA axes and suggest their involvement in key signaling networks in breast cancer, providing a foundation for future functional studies and potential therapeutic targeting
Thymoquinone and 3HQ synergy inhibits CTX-M-15 ESBL
Full text linkBacterial infections remain a significant cause of mortality worldwide, further aggravated by the escalating issue of antibiotic resistance. Extended-Spectrum Beta-Lactamases (ESBLs) pose a substantial challenge, capable of hydrolyzing various beta-lactam antibiotics. The slow pace of drug discovery, coupled with the rapid emergence of drug-resistant bacteria, underscores the urgent need for innovative therapeutic solutions. Thymoquinone (TQ), derived from the seeds of Nigella sativa, has demonstrated notable antibacterial activity against Gram-negative bacteria, including Escherichia coli and Pseudomonas aeruginosa. Previous research has established the efficacy of quinoxaline derivatives, such as 3-hydrazinoquinoxaline-2-thiol (3HQ), against Methicillin-Resistant Staphylococcus aureus (MRSA). This study investigates the potential synergy between 3HQ and TQ against various clinical strains of ESBL. The minimum inhibitory concentrations (MICs) of TQ and 3HQ were evaluated against 18 clinical ESBL strains, revealing MIC values ranging from 16 to 128 µg/mL for both compounds. Furthermore, the interaction between TQ and 3HQ was assessed using a checkerboard assay, which demonstrated a 100% synergistic interaction, with a fractional inhibitory concentration index (FICI) of less than 0.5 against the ESBL strains. Docking and molecular dynamics simulations indicated that TQ exhibits a strong binding affinity and interaction profile comparable to that of RPX-7063. In contrast, 3-hydrazinoquinoxaline-2-thiol targets a different active site, potentially enhancing thymoquinone\u27s binding efficiency. Collectively, these compounds may effectively inhibit CTX-M-15, as evidenced by their docking scores and interaction profiles. Further investigations, including in vivo studies, are essential to validate these findings. This research suggests a promising strategy for developing more effective treatments for ESBL infections, emphasizing the need for in vivo validation
Deep learning predicts HER2 status in invasive breast cancer from multimodal ultrasound and MRI
Full text linkThe preoperative human epidermal growth factor receptor type 2 (HER2) status of breast cancer is typically determined by pathological examination of a core needle biopsy, which influences the efficacy of neoadjuvant chemotherapy (NAC). However, the highly heterogeneous nature of breast cancer and the limitations of needle aspiration biopsy increase the instability of pathological evaluation. The aim of this study was to predict HER2 status in preoperative breast cancer using deep learning (DL) models based on ultrasound (US) and magnetic resonance imaging (MRI). The study included women with invasive breast cancer who underwent US and MRI at our institution between January 2021 and July 2024. US images and dynamic contrast-enhanced T1-weighted MRI images were used to construct DL models (DL-US: the DL model based on US; DL-MRI: the model based on MRI; and DL-MRI&US: the combined model based on both MRI and US). All classifications were based on postoperative pathological evaluation. Receiver operating characteristic analysis and the DeLong test were used to compare the diagnostic performance of the DL models. In the test cohort, DL-US differentiated the HER2 status of breast cancer with an AUC of 0.842 (95% CI: 0.708–0.931), and sensitivity and specificity of 89.5% and 79.3%, respectively. DL-MRI achieved an AUC of 0.800 (95% CI: 0.660–0.902), with sensitivity and specificity of 78.9% and 79.3%, respectively. DL-MRI&US yielded an AUC of 0.898 (95% CI: 0.777–0.967), with sensitivity and specificity of 63.2% and 100.0%, respectively
Is SARS-CoV-2 facing constraints in its adaptive evolution?
Full text linkThe ultimate measure of viral fitness is the ability to maintain high prevalence within its host species. Effective transmission, efficient replication, and rapid immune evasion all contribute to this outcome. Over the past five years, SARS-CoV-2 has successfully adapted to humans, establishing long-term reservoirs and enabling sustained coexistence with the human population. We have observed innovative, synergistic mutations in the spike (S) protein that enhance receptor binding. Adaptation to the upper respiratory tract has shortened the incubation period, thereby facilitating viral spread. These improvements have also enabled immune escape mutations, even when such changes compromise replicative fitness. Adaptive mutations have driven intermittent selective sweeps by dominant variants. However, there are limits to functional enhancement. The receptor binding affinity of the S protein appears to have peaked between 2022 and 2023. The accumulation of fixed mutations plateaued following the emergence of BA.2.86/JN.1 around late 2023 and early 2024. Purifying selection has been the dominant evolutionary force acting on nonsynonymous mutations in the Omicron lineage, and the overall fitness impact of missense mutations in key viral proteins has declined. Additionally, due to weak selection pressure on synonymous mutations, the codon adaptation index in humans has been decreasing among Omicron subvariants. As a result, Omicron lineages have replicated less efficiently in cell cultures compared to the original virus, and recent variants show further attenuation in animal models. In the human population, this attenuation is reflected in declining COVID-19-related mortality, despite persistently high infection rates
Atherogenic index of plasma and risk of diabetic nephropathy in type 2 diabetes: A meta‑analysis
Full text linkThe atherogenic index of plasma (AIP) is a lipid-based biomarker associated with cardiovascular and renal risks in individuals with type 2 diabetes mellitus (T2DM). However, its relationship with diabetic nephropathy (DN) remains inadequately defined. This meta-analysis aims to assess the association between AIP and DN in T2DM patients. We conducted a comprehensive search in PubMed, Embase, and Web of Science for observational studies that compared the incidence or prevalence of DN across varying AIP levels in T2DM populations. Data were synthesized using a random-effects model to account for potential heterogeneity. A total of eleven datasets from ten studies, encompassing 25,773 T2DM patients, were included in the analysis. The pooled results indicated that higher AIP levels are significantly associated with DN (risk ratio [RR] = 1.51, 95% confidence interval [CI]: 1.36–1.67; p < 0.001). Subgroup analyses revealed a stronger association in patients aged 58 years or older (RR = 1.66) compared to those younger than 58 years (RR = 1.35; p for subgroup difference = 0.02). Similar associations were observed across different study designs, sex distributions, AIP cutoff values, definitions of DN, and quality scores (p for subgroup difference all > 0.05). Meta-regression analysis further indicated that older age positively influenced the strength of the association (coefficient = 0.018, p = 0.03). In conclusion, elevated AIP levels are significantly associated with diabetic nephropathy in T2DM patients, particularly among older individuals
Erratum: Rab8a/SNARE complex activation promotes vesicle anchoring and transport in spinal astrocytes to drive neuropathic pain
Full text linkIn the article “Rab8a/SNARE complex activation promotes vesicle anchoring and transport in spinal astrocytes to drive neuropathic pain” (Xiao et al., DOI: https://doi.org/10.17305/bb.2024.10441), published on 6 September 2024, an incorrect version of Figure 2 was inadvertently published due to an editorial oversight. The article has been corrected online to include the accurate figure. This correction does not affect the study’s results, interpretations, or conclusions. We apologize for the error and thank the authors for bringing it to our attention
Vitamin D deficiency and uterine leiomyoma in unexplained infertility
Full text linkUterine leiomyomas are the most common benign tumors of the female genital tract, and alongside hormonal and genetic factors, emerging evidence implicates vitamin D deficiency in their pathogenesis. We investigated the association between serum 25-hydroxyvitamin D [25(OH)D] and the presence of uterine leiomyomas in women with unexplained infertility. In this retrospective case–control study, 148 women aged 18–45 years presenting to the Infertility Clinic of Ankara Bilkent City Hospital between July 2019 and February 2024 were included: 74 had imaging-confirmed leiomyomas (non-submucosal; FIGO types 4–6) and 74 infertile controls had no leiomyomas. Serum 25(OH)D was measured and demographic/clinical data were analyzed with appropriate parametric and non-parametric tests; correlations used Spearman’s rho, and an ANCOVA adjusted for body mass index (BMI) and season assessed group differences. Groups were comparable in age and BMI (e.g., age 35.08 ± 5.79 vs 33.30 ± 5.57 years; p = 0.062). Mean serum 25(OH)D was significantly lower in women with leiomyomas than in controls (41.4 ± 23.7 vs 62.0 ± 34.2 nmol/L; p < 0.001), and this difference remained significant after adjustment for BMI and season (ANCOVA F = 10.7, p = 0.001). Vitamin D levels did not differ by leiomyoma number (single vs multiple: 44.1 ± 21.6 vs 38.5 ± 25.83 nmol/L; p = 0.32) or location (intramural vs subserosal: 40.7 ± 24.9 vs 43.1 ± 21.1 nmol/L; p = 0.69), and were not correlated with leiomyoma size (Spearman r = −0.04; p = 0.70). Among women with unexplained infertility, uterine leiomyomas are thus associated with significantly lower serum 25(OH)D levels, independent of BMI and season, whereas vitamin D status is unrelated to leiomyoma number, size, or location. These findings support a potential role of vitamin D deficiency in leiomyoma pathogenesis and underscore the need for larger, multicenter prospective studies to clarify causality and clinical implications
Lactylation in ischemic brain injury—metabolic mechanisms, neuroinflammation, and therapeutic targets: A review
Full text linkCerebral ischemic injury, a major cause of mortality and disability, results from reduced or interrupted blood flow to the brain, most commonly in ischemic stroke. Insufficient oxygen and nutrient supply disrupts cellular metabolism, leading to neuronal death, neurological dysfunction, and lasting impairments. Current therapeutic strategies, including thrombolysis, mechanical thrombectomy, and anticoagulation, primarily aim to restore perfusion and provide neuroprotection by preserving the ischemic penumbra. While these interventions can partially rescue viable tissue in the acute phase, their effectiveness is constrained by narrow therapeutic windows, low recanalization rates, and contraindications, leaving significant unmet clinical needs. Consequently, the search for novel, targeted approaches has become a central focus of ischemic stroke research. Recent discoveries have identified lactylation, a newly recognized post-translational modification derived from lactate, as a key regulator of gene expression, protein function, and metabolic reprogramming. Once regarded as a simple glycolytic byproduct, lactate is now known to act as both an alternative energy substrate and a signaling molecule, influencing neuronal metabolism, antioxidant defense, and inflammatory responses. In ischemic brain injury, lactylation modifications of histone and non-histone proteins may either protect neurons—by supporting energy homeostasis, regulating stress-responsive genes, and suppressing apoptosis—or exacerbate injury through neuroinflammation, excitotoxicity, and immune evasion. Evidence indicates that the outcomes of lactylation depend on lactate concentration, timing of accumulation, cell type, and the balance between “writer” and “eraser” enzymes. Therefore, lactylation emerges as a promising yet complex therapeutic target in cerebral ischemia. Modulating lactate metabolism and its downstream modifications offers new opportunities to expand the therapeutic window, attenuate neuronal injury, and improve recovery. This review summarizes the molecular mechanisms linking lactate and lactylation to ischemic injury, highlights current contradictions in experimental findings, and explores the potential of targeting lactylation pathways for innovative treatment strategies
Childhood obesity and allergic rhinitis: A meta-analysis
Full text linkAllergic rhinitis (AR) is a prevalent chronic condition in childhood, and its increasing incidence has prompted research into potential associations with modifiable factors such as obesity. This meta-analysis aimed to assess the multivariate-adjusted relationship between childhood obesity and AR. A systematic search was conducted across PubMed, Embase, and Web of Science for observational studies that reported on the association between obesity and AR in children. Only studies that included multivariate adjustments for at least age and sex were considered. Random-effects models were employed to pool odds ratios (ORs) with 95% confidence intervals (CIs), accounting for heterogeneity. Fifteen cross-sectional studies comprising 23 datasets involving a total of 569,856 children were included in the analysis. The overall results indicated that obesity was not significantly associated with AR (adjusted OR: 1.04, 95% CI: 1.00–1.09; p = 0.08; I² = 24%). However, subgroup analyses revealed a significant association in Western countries (OR: 1.12, 95% CI: 1.00–1.24; p = 0.04; I² = 0%), while no significant association was found in Asian countries (OR: 1.04, 95% CI: 0.97–1.12; p = 0.27; I² = 52%). Notable associations were identified in studies utilizing national or international BMI cutoffs (OR: 1.06, 95% CI: 1.01–1.10; p = 0.02) and those with physician-diagnosed AR (OR: 1.07, 95% CI: 1.02–1.13; p = 0.006), but not in studies employing the 95th percentile BMI definition or ISAAC-based AR diagnosis. No significant differences were observed based on age or sex. Meta-regression analysis indicated that age, sex, and study quality score did not significantly influence the results (p all > 0.05). Egger’s test revealed no evidence of publication bias (p = 0.43). In conclusion, while no significant overall association between childhood obesity and AR was found, subgroup analyses suggest potential links within specific populations and under particular methodological definitions. These findings should be interpreted with caution, and further longitudinal studies are necessary to determine whether preventive strategies aimed at reducing childhood obesity may also impact allergic outcomes
Succinylcholine-induced rhabdomyolysis in a patient with RYR1 and BCHE variants: A case report
Full text linkMasseter muscle spasm after succinylcholine can herald malignant hyperthermia (MH) in genetically susceptible individuals. We aimed to describe the perioperative course and genetic findings in a patient who developed transient masseter spasm and postoperative rhabdomyolysis after general anesthesia. This single-patient case report draws on perioperative observations, laboratory testing, and whole-genome sequencing. Immediately after induction with propofol and succinylcholine, the patient experienced transient masseter spasm; anesthesia was then maintained with total intravenous anesthesia (propofol and remifentanil). Postoperatively, laboratory studies showed severe rhabdomyolysis with mild pigment nephropathy; the patient received intravenous hydration, laboratory values normalized by postoperative day 4, and discharge occurred in good condition. Whole-genome sequencing identified heterozygous ryanodine receptor 1 (RYR1) c.1840C>T (p.Arg614Cys)—a known MH-susceptibility variant in the skeletal-muscle ryanodine receptor—and butyrylcholinesterase (BCHE) c.293A>G (p.Asp98Gly), which reduces butyrylcholinesterase activity and delays succinylcholine hydrolysis. The coexistence of these variants likely synergistically increased sarcoplasmic reticulum Ca²⁺ release and prolonged succinylcholine effect, precipitating rhabdomyolysis; to our knowledge, this appears to be the first reported case linking concurrent RYR1 and BCHE variants to rhabdomyolysis following general anesthesia