Bosnian Journal of Basic Medical Sciences (BJBMS)
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Caffeine toxicity in zebrafish – Neurobehavioral changes, developmental defects, and oxidative stress: A review
Full text linkCaffeine is one of the most widely consumed psychoactive stimulants, primarily functioning as a non-selective adenosine receptor antagonist. Its increasing detection in wastewater and surface waters reflects extensive anthropogenic use. This review synthesizes evidence from zebrafish (Danio rerio)—a genetically tractable vertebrate with rapidly developing external embryos—to assess the impact of caffeine exposure across environmentally relevant (ng–µg/L) and pharmacological/toxicological (mg/L and above) concentrations on early development and neurobehavior. Behavioral studies indicate dose- and stage-dependent alterations in locomotion, anxiety-like responses, memory performance, and sleep patterns, suggesting disruptions in neural circuitry and stress-axis regulation. Biochemical analyses frequently reveal oxidative imbalances characterized by increased reactive oxygen species and lipid peroxidation, alongside changes in antioxidant defenses (e.g., glutathione levels, superoxide dismutase (SOD) activity, and glutathione reductase activity). These findings support oxidative stress as a potential mechanistic hub, although a causal relationship has yet to be established. Embryonic exposure to caffeine is associated with developmental toxicity, including delayed hatching and concentration-dependent malformations such as edema, axial deformities, impaired angiogenesis, and neuromuscular defects at higher doses. However, cross-study comparisons are hindered by variations in units, exposure durations, and assay protocols. In summary, caffeine disrupts behavior, redox homeostasis, and developmental processes in zebrafish, highlighting the necessity for standardized methodologies to identify stage-specific vulnerabilities
Complementary therapies in early breast cancer: Oncologists’ evidence-based decisions in a Southeast European vignette survey
Full text linkComplementary therapies are increasingly integrated into the framework of integrative oncology. While numerous complementary therapies provide potential benefits, some may also carry risks, including interactions with conventional cancer treatments. The degree to which oncologists\u27 real-world decisions regarding complementary therapies align with evidence-based guidelines remains uncertain. This study aimed to evaluate oncologists\u27 evidence-based decisions on whether specific complementary therapies should be prohibited, permitted, or recommended for early breast cancer treatment. We conducted a cross-sectional online survey that included a randomized vignette experiment involving oncology specialists and residents from seven Southeast European countries. The primary outcome was the percentage of accurate classifications of 28 therapy-indication pairs in neoadjuvant and adjuvant settings, benchmarked against published evidence. Correctness was assessed using both a strict definition (one correct option) and an expanded definition (accepting "allow" or "recommend" when supported by evidence). A total of 136 respondents met the inclusion criteria and provided paired responses. Median accuracy was found to be 52% (95% CI 48-55) under the strict definition and 70% (95% CI 67-72) under the expanded definition, with no significant differences observed between neoadjuvant and adjuvant settings. Evidence-based therapies, such as physical exercise and cognitive behavioral therapy, were most frequently recommended, whereas most other therapies received endorsement from fewer than 25% of respondents. Overall, oncologists exhibited moderate alignment with evidence, demonstrating a tendency to permit rather than actively recommend complementary therapies, even when evidence indicated potential benefits and safety. These findings underscore the necessity for targeted educational interventions aimed at enhancing oncologists\u27 understanding and ensuring the safe and informed integration of complementary therapies into clinical practice
Exploring the link between environmental chemical exposures and epigenetic modifications in diabetes mellitus: A review
Full text linkDiabetes mellitus (DM) is a globally prevalent metabolic disorder characterized by impaired glucose homeostasis and insulin secretion. Beyond traditional risk factors like lifestyle and genetics, environmental pollutants, including particulate matter, heavy metals, and persistent organic pollutants, have become significant contributors to DM. One of the key mechanistic pathways through which these pollutants exert their effects is the activation of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that regulates the expression of cytochrome P450 family 1 (CYP1) enzymes. This cascade contributes to increased oxidative stress and systemic inflammation, hallmarks of metabolic impairment. Importantly, these environmental pollutants are also linked to epigenetic modifications, including aberrant DNA methylation, histone modifications, and microRNA dysregulation, which further disrupt insulin sensitivity and β-cell function. This review explores the possible mechanistic crosstalk between AhR/CYP1 pathway activation and epigenetic alterations in the context of diabetes development. By integrating findings from epidemiology, in vivo, and in vitro studies, we provide a summary of how environmental exposures may influence diabetes risk through epigenetic mechanisms. Understanding these interactions not only advances our knowledge of DM etiology but also highlights novel molecular targets for preventive and therapeutic strategies
Silencing CACYBP suppresses lung adenocarcinoma growth via CDK1 inhibition
Full text linkCalcyclin-binding protein (CACYBP) is a multidomain adaptor protein implicated in the development of various cancers. However, its molecular and biological roles in lung adenocarcinoma (LUAD) remain unclear. In this study, we aimed to elucidate the biological impact of CACYBP in LUAD. Immunohistochemistry was used to assess CACYBP expression in LUAD tissues. Lentivirus-mediated CACYBP knockdown was established in LUAD cell lines, and target gene expression was analyzed via Western blotting and qRT-PCR. Cell proliferation, apoptosis, and migration were evaluated using flow cytometry, colony formation assays, cell counting kit-8 (CCK 8) assays, Celigo cell counting, wound healing assays, Transwell assays, and mouse xenograft models. Co-immunoprecipitation was performed to verify the interaction between CACYBP and cyclin-dependent kinase 1 (CDK1). Additionally, the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was used to investigate the involvement of CDK1 in the PI3K/AKT pathway. Our findings revealed that CACYBP was upregulated in LUAD tissues and correlated with advanced disease stages and poor prognosis. CACYBP knockdown inhibited LUAD progression and metastasis, promoted cell apoptosis in vitro, and reduced tumorigenicity in vivo. Mechanistically, we identified CDK1 as a direct interacting partner of CACYBP. CDK1 overexpression enhanced the malignant phenotype of LUAD cells and partially reversed the inhibitory effects of CACYBP knockdown. Furthermore, inhibition of the PI3K/AKT pathway using LY294002 significantly suppressed CDK1-mediated LUAD cell growth. In conclusion, CACYBP appears to function as a tumor promoter in LUAD, at least in part through CDK1-mediated activation of the PI3K/AKT pathway. These findings suggest that CACYBP could serve as a promising therapeutic target and a novel biomarker for LUAD prognosis
Enhancing predictions of health insurance overspending risk through hospital departmental performance indicators
Full text linkThe substantial rise in health insurance expenditures, combined with delayed feedback on overspending from administrative departments, highlights the urgent need for timely reporting of such data. This study analyzed a large cohort of 549,910 discharged patients\u27 medical records from the Wuxi Health Commission, covering the period from January 2022 to November 2023. We applied four widely recognized machine learning techniques—Logistic Regression (LR), LightGBM, Random Forest (RF), and Artificial Neural Networks (ANN)—alongside departmental performance indicators (DPIs) to develop Insurance Overspending Risk Prediction (IORP) models at both regional and hospital levels. The dataset was divided into training and testing sets in a 7:3 ratio. Experimental results showed that LightGBM outperformed the other models, achieving an accuracy of 0.82 for both regional and hospital-level predictions. Its weighted F1-score reached 0.78 at the regional level and 0.82 at the hospital level, with corresponding AUC-ROC (Area Under the Receiver Operating Characteristic Curve) values of 0.91 and 0.94, demonstrating strong performance in identifying overspending risks. The model’s high recall and precision further ensure reliable predictions and minimize misclassifications. Notably, four key DPIs—Total Amount of Discharged Patients (TADP), Average Inpatient Stay (AIS), Medicine Expenses Percentage (MEP), and Consumable Expenses Percentage (CEP)—were strongly correlated with overspending risks. The integration of IORP models into the Health Insurance Management System (HIMS) at the Affiliated Hospital of Jiangnan University has significantly improved departmental managers\u27 ability to anticipate overspending. By effectively leveraging HIMS in combination with this advanced model, managers can perform timely, accurate assessments, thereby enhancing financial oversight and resource allocation
Green synthesis of plant-derived ZnO nanoparticles: Characterization, pharmacokinetics, molecular interactions, and in-vitro antimicrobial and antifungal evaluation
Full text linkNowadays, nanoparticles (NPs) are used to counteract various medicinal and industrial problems. This study aimed to biosynthesize zinc oxide NPs (ZnONPs) from the plant species Aloe vera L., Peganum harmala L., Retama monosperma L., and Thymelaea hirsuta L. The biosynthesized ZnONPs were referred to as “Thymhirs.bio-ZnONP,” “Aloever.bio-ZnONP,” “Retam.bio-ZnONP,” and “Harm.bio-ZnONP.” A UV-visible spectrophotometer, granulometry, Fourier transform infrared spectroscopy, and electron paramagnetic resonance were used for physicochemical characterization. Pharmacokinetics and antimicrobial effects were explored using combined in vitro and computational assays. An abundance of phenolic acids and flavonoids was observed, particularly rutin, quinic acid, apigenin-7-O-glucoside, and cirsiliol, which may act as reducing, stabilizing, and capping agents in the biosynthesis. ZnONPs demonstrated strong antimicrobial activity against various bacterial, fungal, and yeast strains, highlighting their potential medicinal applications. This inhibitory activity can be attributed to the effect of the plant-based ZnO nanosized particles more than to the plant extracts or Zn salt. Computational modeling revealed that the identified phytochemicals (phenolic acids and flavonoids) bound Tyrosyl-tRNA Synthetase (TyrRS) from S. aureus (1JIJ), aspartic proteinase from C. albicans (2QZW), and wheat germ agglutinin (2UVO) with considerable affinities, which, together with molecular interactions and pharmacokinetics, satisfactorily support the in vitro antimicrobial findings. This study lays the groundwork for future research and pharmaceutical explorations aimed at harnessing the likely beneficial properties of green-synthesized ZnONPs for medicinal and therapeutic purposes, particularly their antimicrobial effects
Association of serum Netrin-1, NSE, and S100β with brain injury severity and prognosis in patients with sepsis-associated encephalopathy
Full text linkSepsis-associated encephalopathy (SAE) represents the most prevalent neurological complication of sepsis and is frequently linked to unfavorable patient outcomes. This study aimed to evaluate the prognostic significance of serum Netrin-1, neuron-specific enolase (NSE), and S100β levels in patients diagnosed with SAE. A retrospective analysis was performed on 120 SAE patients, measuring serum levels of Netrin-1, NSE, and S100β and correlating these with Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores. Independent risk factors for short-term mortality were identified, and the predictive values of these biomarkers were assessed both individually and in combination. Kaplan-Meier analysis was utilized to compare short-term mortality based on biomarker levels. Netrin-1 was found to be significantly downregulated, while NSE and S100β levels were upregulated in SAE patients. Lower levels of Netrin-1, alongside higher levels of NSE and S100β, correlated with elevated APACHE-II scores and increased short-term mortality. Multivariate analysis confirmed that all three biomarkers serve as independent predictors of short-term mortality. The combined assessment of Netrin-1, NSE, and S100β demonstrated superior prognostic value compared to individual biomarker. Therefore, serum levels of Netrin-1, NSE, and S100β are closely associated with the severity of brain injury in SAE and serve as effective predictors of short-term mortality, enhancing prognostic accuracy in clinical practice
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.
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
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