Bosnian Journal of Basic Medical Sciences (BJBMS)
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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
Plasma Sestrin2 levels and risk of acute ischemic stroke: A case–control study
Full text linkSestrin2, a stress-inducible protein with antioxidant properties, is upregulated in response to various stressors, including oxidative and energetic stress. This study examines the relationship between plasma Sestrin2 levels, total antioxidant capacity (TAC), total nitric oxide (NO), and the likelihood of experiencing an acute ischemic stroke (AIS) within the Qatari population. The cohort consisted of 187 AIS patients and 30 healthy controls. Plasma concentrations of Sestrin2, TAC, and nitrite/nitrate (an indirect measure of NO) were evaluated at four intervals: within 48 hours of stroke onset, and at 5 days, 30 days, and 1 year post-stroke. At stroke onset, AIS patients exhibited significantly lower plasma levels of Sestrin2 (1.434±3.57 vs. 8.383±7.39; p <0.001), TAC (1.88±0.42 vs. 2.279±0.326; p <0.001), and nitrite/nitrate (53.5±47.9 vs. 65.951±44.07; p = 0.04) compared to controls. Sestrin2 levels remained diminished at 5 and 30 days post-stroke, while NO levels increased by day 5 (p = 0.01). Multiple logistic regression analysis revealed that male sex, diabetes, high National Institutes of Health Stroke Scale (NIHSS) scores, and small vessel disease (SVD) were associated with increased odds of AIS, whereas Middle Eastern ethnicity correlated with reduced odds. Notably, higher tertiles of Sestrin2, TAC, and NO were linked to decreased odds of AIS, with adjusted odds ratios of 0.123 (p < 0.001), 0.327 (p = 0.01), and 0.063 (p = 0.01), respectively. The observed lower plasma levels of Sestrin2, TAC, and NO at stroke onset and up to 30 days post-event suggest their potential role as biomarkers in stroke occurrence and recovery, with elevated levels associated with a decreased likelihood of AIS
Sclerostin antibody promotes alveolar bone regeneration after tooth extraction
Full text linkSclerostin is a key inhibitor of the Wnt signaling pathway, functioning by binding to the LRP5/6 receptor. This interaction inhibits beta-catenin expression, resulting in the downregulation of osteogenic markers, which contributes to the promotion of osteoporosis and an increase in osteoclast numbers. The primary objective of this research was to investigate the effects of sclerostin antibody (Scl-ab) on bone formation utilizing graft materials in tooth sockets, and to analyze the regulatory interaction between sclerostin and bone tissue through targeted sclerostin inhibition and stimulation of bone formation in tooth extraction sockets following local, single-dose administration. In this study, New Zealand male rabbits (3 months old, weighing 2.5-3 kg) were fully randomized to minimize bias. The experiments were conducted across five groups: a control group, a graft group, and three experimental groups receiving 100%, 75%, and 50% doses of Scl-ab. Calculated doses of Scl-ab were administered alongside the graft material in the extraction sockets, with results assessed at 2 and 4-week intervals. Cone-beam computed tomography indicated that the tooth extraction sockets treated with varying ratios of Scl-ab with graft material exhibited a statistically significant increase in the mean mandibular BV/TV ratio compared to the control and graft groups, with variations based on time and dosage. While bone volume improved over time, the most significant enhancement was observed in the 100% Scl-ab group. Additionally, the administration of different doses of Scl-ab significantly increased trabecular thickness of the alveolar bone compared to both the control (p < 0.001) and graft (p < 0.001) groups, with histological analysis corroborating these findings. The therapeutic application of Scl-ab facilitates early bone formation, and the localized inhibition of sclerostin secreted within the bone microenvironment targets potential bone regeneration.
Maternal smoking during pregnancy and risk of childhood-onset type 1 diabetes in offspring: A systematic review and meta-analysis
Full text linkChildhood-onset type 1 diabetes (T1D) is a chronic autoimmune disease characterized by a steadily increasing global incidence and significant public health implications. The relationship between maternal smoking during pregnancy and T1D risk remains uncertain. To clarify this association, we conducted a meta-analysis of prospective cohort studies to enhance methodological reliability. We systematically searched PubMed, Embase, and Web of Science from their inception to May 2025 for prospective cohort studies examining the link between maternal smoking during pregnancy and the incidence of T1D in offspring. Risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model, accounting for heterogeneity. Twelve prospective cohort datasets from ten studies, encompassing over 5.9 million children, were included. Maternal smoking during pregnancy was significantly associated with a reduced risk of childhood-onset T1D (RR: 0.74, 95% CI: 0.72–0.76, p < 0.001), with no evidence of statistical heterogeneity (I² = 0%, p = 0.48). This association remained robust across sensitivity analyses that excluded one dataset at a time. Subgroup analyses demonstrated consistent results across various categories, including cohort size, prevalence of maternal smoking, method of T1D diagnosis, and adjustments for maternal age, diabetes, and delivery mode. Notably, the inverse association was significantly weaker in studies that did not adjust for maternal diabetes (RR: 0.79 vs. 0.72, p for subgroup difference = 0.01). We found no substantial evidence of publication bias (Egger’s test, p = 0.55). In conclusion, this meta-analysis identified an inverse association between maternal smoking during pregnancy and the incidence of childhood-onset T1D. However, this finding should be interpreted cautiously, as residual confounding cannot be ruled out, and maternal smoking is associated with numerous serious adverse health consequences
Circulating organokines in coronary artery disease and metabolic syndrome: FABP4, adiponectin, irisin, FSTL1
Full text linkCardiovascular disorders are closely linked to metabolic syndrome and remain a leading cause of mortality worldwide, despite advances in early detection and treatment. Adipokines, cardiokines, and myokines play critical roles in maintaining systemic metabolic homeostasis. In this study, we measured serum levels of fatty acid binding protein 4 (FABP4), follistatin-like 1 (FSTL1), irisin, and adiponectin in 243 male patients undergoing elective coronary angiography. We investigated the associations of these biomarkers with coronary artery disease (CAD) and their correlation with metabolic syndrome status. FSTL1 levels were predicted using a Particle Swarm Optimization-enhanced Adaptive Neuro-Fuzzy Inference System (PSO-ANFIS) based on artificial intelligence. Patients with CAD exhibited significantly lower FABP4 levels (p<0.0001), and low FABP4 levels emerged as an independent predictor of CAD in logistic regression analysis (odds ratio 0.903, 95% CI 0.825-0.987, p=0.025). The combination of adiponectin, FSTL1, and irisin as a biomarker strategy demonstrated high sensitivity and specificity for diagnosing metabolic syndrome (AUC = 0.92, 95% CI 0.88-0.96). Both FSTL1 and adiponectin independently correlated with metabolic syndrome (p<0.001, odds ratio 1.039, 95% CI 1.025-1.054; p<0.001, odds ratio 0.979, 95% CI 0.971-0.988, respectively). The prediction of FSTL1 levels using PSO-ANFIS supports the concept of harmonization among metabolic messengers. These findings underscore the potential of FABP4 and FSTL1 as valuable biomarkers for diagnosing metabolic and cardiovascular diseases, thereby facilitating personalized interventions targeting organokine pathways
Hypochlorite sensing and real-time imaging with XY-01: A red-emitting fluorescent turn-on probe for living cells and colorectal cancer organoids
Full text linkHypochlorite (ClO⁻), a major reactive oxygen species generated in inflammation, is a potent biological oxidant involved in diverse physiological and pathological processes; therefore, sensitive detection of ClO⁻ is important for understanding disease pathophysiology and supporting early diagnosis and prevention. Here, we aimed to develop a physiologically compatible fluorescent tool for specific ClO⁻ sensing and imaging. We designed and synthesized a novel A–D–A type molecular fluorescent probe, XY-01, and characterized it by NMR, HRMS, UV–Vis and fluorescence spectroscopy. XY-01 operates through ClO⁻-triggered oxidation of a thioformyl group (C=S) to a carbonyl (C=O), which restores intramolecular charge transfer and produces a prominent fluorescence turn-on signal. In PBS (pH 7.4), XY-01 responded to ClO⁻ within 1 min with strong red emission at 666 nm and a large Stokes shift (~167 nm), showed high selectivity against common ions and reactive species, and achieved a detection limit of 3.39 µM within the biologically relevant range. Cytotoxicity assays indicated negligible toxicity, enabling real-time confocal imaging of ClO⁻ distribution in HCT-116 cells and colorectal cancer organoids. Collectively, XY-01 is a simple, sensitive, and low-toxicity probe that provides a promising platform for optical sensing and imaging of hypochlorite in living cells and organoids
Genetic determinants of lipid metabolism in cardioprotection: From mechanisms to clinical practice
Full text linkAtherosclerotic cardiovascular diseases continue to be the leading causes of morbidity and mortality globally. Disorders of lipoprotein metabolism contribute significantly to the development of atherosclerosis, which begins with the subendothelial retention of plasma-derived apolipoprotein B-containing lipoproteins, particularly low-density lipoprotein (LDL) and its remnants. Elevated LDL cholesterol levels and triglycerides, coupled with low high-density lipoprotein (HDL) cholesterol levels, are critical risk factors for atherosclerotic cardiovascular diseases. Landmark epidemiological studies have identified dyslipidemia as a key modifiable risk factor for these diseases, elucidating the essential role of lipid abnormalities in atherogenesis and highlighting significant opportunities for cardiovascular disease prevention and risk stratification. Genetic epidemiology studies have shown that lifelong low levels of LDL due to genetic variations markedly reduce the risk of atherosclerotic cardiovascular diseases. Recent advancements in lipid-lowering pharmacology are increasingly informed by genetic studies that reveal naturally occurring mutations offering lifelong cardioprotection. Furthermore, these genetic studies have facilitated the development of novel therapeutics and enhanced the prediction of potential side effects, variability in individual drug responses, and improved risk stratification. This narrative review article aims to summarize key genetic variants that influence lipid metabolism and examine their therapeutic potential in cardiovascular therapy. Given the central role of atherosclerosis in determining cardiovascular risk, it is vital to consider lipid metabolism in the context of genetic factors that affect individual susceptibility to hyperlipidemia. Defining cardioprotective genetic determinants is equally important, as it may provide a foundation for therapeutic strategies by emphasizing protective mechanisms
Gut microbiota-derived extracellular vesicles in Alzheimer’s disease – Immunomodulatory mechanisms, biomarkers, and therapeutic opportunities: A review
Full text linkAlzheimer\u27s disease (AD) is a progressive neurodegenerative disorder that poses a growing global health challenge. Beyond traditional hallmarks such as amyloid-β (Aβ) deposition, tau hyperphosphorylation, and neuroinflammation, the gut–brain axis (GBA) has emerged as a significant modulator of AD pathogenesis. Among gut-derived mediators, microbiota-derived extracellular vesicles (mEVs) transport bioactive cargo across epithelial and vascular barriers, thereby linking intestinal dysbiosis to neurodegeneration. This narrative review synthesizes experimental, translational, and early clinical evidence regarding the immunomodulatory roles of gut mEVs in AD. We examine how mEVs may traverse compromised intestinal and blood–brain barriers, activate microglia and astrocytes, and influence Aβ and tau metabolism, thereby integrating peripheral and central immune interactions. Based on this evidence, we propose the "microbiota–EV–immune–neuro axis" as a conceptual framework that connects gut dysbiosis with AD-related neurodegeneration. The review also highlights emerging data on mEV signatures as minimally invasive biomarkers and explores their potential as therapeutic targets or delivery vectors. While current evidence is preliminary and methodologically heterogeneous, mEVs are increasingly recognized as both indicators and potential modulators of AD pathophysiology, emphasizing the need for standardized, longitudinal, and interventional studies
Plasma serotonin precursors and metabolites as diagnostic and therapeutic biomarkers for osteoporosis in postmenopausal women
Full text linkThis study aims to evaluate the diagnostic and therapeutic potential of plasma 5-hydroxytryptamine (5-HT) precursors and metabolites in postmenopausal osteoporosis (PMOP). A total of 287 consecutive postmenopausal women were retrospectively enrolled. Data including age, body mass index (BMI), serum calcium, serum phosphorus, menopausal duration, and bone mineral density (BMD) of the lumbar spine and femoral neck, as well as serum and plasma samples were collected. Based on BMD measurements, participants were categorized into normal, osteopenia, and osteoporosis (OP) groups. Serum β-CTX and PINP, along with plasma levels of 5-HT precursors and metabolites, were measured using ELISA. Receiver operating characteristic (ROC) curve analysis, multivariate analysis, and Kaplan-Meier curves were employed to assess the predictive value of 5-HT precursors and metabolites in PMOP and to evaluate the association between their expression levels and PMOP risk. Plasma levels of 5-hydroxytryptophan (5-HTP), 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) were elevated in PMOP patients and showed correlations with bone turnover markers and BMD. These biomarkers were identified as independent risk factors for PMOP. Combined analysis of the three biomarkers demonstrated greater predictive value than individual markers. Elevated levels were particularly pronounced in women with ≥ 12 years since menopause (YSM), and were associated with a higher risk of developing PMOP. In summary, 5-HT precursors and metabolites are significantly associated with bone turnover and BMD in postmenopausal women. They serve as independent risk factors and show strong predictive value for PMOP, suggesting their potential as plasma biomarkers for diagnosis and treatment. Furthermore, their relationship with YSM highlights their promise as therapeutic targets to delay the onset of osteoporosis in postmenopausal women.
APOC1 knockdown induces apoptosis and decreases angiogenesis in diffuse large B-cell lymphoma cells through blocking the PI3K/AKT/mTOR pathway
Full text linkDiffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous metastatic lymphoma that can be treated by targeting angiogenesis. Apolipoprotein C1 (APOC1) plays a significant role in the proliferation and metastasis of various malignant tumors; however, its role in DLBCL—particularly its effects on angiogenesis—remains largely unexplored. This study investigates the correlation between APOC1 expression and patient prognosis in DLBCL. Using APOC1 gene knockdown, apoptosis, migration, and invasion were assessed through flow cytometry, the EDU assay, wound healing, and Transwell assays. Additionally, human umbilical vein endothelial cells (HUVEC) angiogenesis was evaluated. Advanced techniques, such as immunofluorescence, TUNEL assay, and immunohistochemical labeling were employed to analyze the effects of APOC1 knockdown on the PI3K/AKT/mTOR signaling pathway and tumor formation in nude mice. Results showed that APOC1 is overexpressed in DLBCL tissues and cells, with high APOC1 levels associated with poor patient prognosis. In vitro experiments revealed that APOC1 knockdown increased apoptosis and inhibited cell proliferation, migration, invasion, HUVEC angiogenesis, and PI3K/AKT/mTOR signaling pathway protein expression in DLBCL cells. Similarly, in vivo studies demonstrated that APOC1 knockdown significantly reduced tumor growth, angiogenesis-related proteins, and phosphorylated PI3K/AKT/mTOR pathway proteins in nude mice. APOC1 knockdown promotes apoptosis and suppresses angiogenesis in DLBCL cells by inhibiting the PI3K/AKT/mTOR pathway