Bosnian Journal of Basic Medical Sciences (BJBMS)
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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
Letrozole versus coenzyme Q10 plus Clomiphene citrate for women with Polycystic Ovarian Syndrome: An efficacy and safety analysis
Full text linkClomiphene citrate is a well-established treatment for Polycystic Ovarian Syndrome (PCOS) but has poor efficacy and adverse effects. Coenzyme Q10 supplementation improves mitochondrial function. Letrozole has been reported to be effective with fewer adverse effects but is not approved for PCOS by the USFDA. This is a retrospective study in women diagnosed with PCOS to assess treatment with either 2.5 mg/day letrozole (LO cohort, n = 103) for 5 days per cycle (for 9 cycles). The QC group received additional doses of 50 mg coenzyme Q10 three times daily (QC cohort, n = 123). A third group received only 100 mg/day clomiphene citrate (CC cohort, n = 155) from the second day of the menstrual cycle for 5 days. After treatment, the duration of the menstrual cycle decreased across all cohorts (P < 0.001 for all), with a smaller reduction observed in the LTZ cohort compared to the QC and CC cohorts (P < 0.05 for all). The number of conceived pregnancies in the LTZ cohort (P < 0.0001) and the CC + QC cohort (P < 0.0001) was significantly higher than in the CC only group. Similarly, conception was higher in the CC + Q10 group than in the CC only group (P < 0.0001 for both groups). Letrozole versus clomiphene citrate plus coenzyme Q10 showed similar efficacy in achieving pregnancy in women with PCOS
Mesenchymal stem cell- derived exosomes as cell-free therapeutics for sensorineural hearing loss
Full text linkSensorineural hearing loss (SNHL) can result from various factors, including ototoxic drugs (such as aminoglycosides and chemotherapeutic agents), prolonged exposure to intense sound, and autoimmune or genetic disorders. In adult mammals, the loss of sensory cells in the cochlea is irreversible due to their lack of regenerative capacity. Current treatment options include hearing aids for mild to moderate hearing loss, which rely on residual hearing, and cochlear implants for severe cases, which provide limited auditory recovery while leading to the loss of any remaining natural hearing. Stem cell therapies, particularly those involving mesenchymal stem cells (MSCs), are being increasingly explored in regenerative medicine. MSCs are multipotent cells capable of differentiating into mesodermal lineage cells and possess immunomodulatory and regenerative properties, making them potential candidates for SNHL treatment. However, their administration carries risks, including unwanted differentiation, immune system activation, and potential tumorigenic effects. Exosomes, extracellular vesicles in the nanometer size range, are secreted by most eukaryotic cells. These vesicles, which have a double lipid membrane and contain genomic and proteomic material, play a crucial role in intercellular communication. Exosomes derived from MSCs exhibit similar biological functions to their parent cells but with significantly lower risks, as they do not trigger immune responses or pose oncological concerns. This paper aims to review current knowledge on the use of MSCs and MSC-derived exosomes for inner ear sensory cell regeneration and explore their potential for clinical applications
Adipose-derived MSC extracellular vesicles ameliorate sepsis by reprogramming macrophages via miR-21-5p targeting PELI1
Full text linkSepsis is a common and life-threatening condition encountered in intensive care units (ICUs). Mesenchymal stromal cells (MSCs) and their small extracellular vesicles (EVs) have emerged as promising nanotherapeutics, particularly in the context of COVID-19. This study evaluates the efficacy and mechanisms of adipose-derived MSC EVs (ADMSC-EVs) in a lipopolysaccharide (LPS)-induced sepsis model. We quantified M2 macrophages and IL-10 in peripheral blood mononuclear cells (PBMCs) from both septic patients and healthy donors. ADMSCs and their EVs were isolated, and EVs were administered to LPS-challenged mice. Macrophage phenotypes in lung tissue were analyzed using flow cytometry and immunofluorescence. The biodistribution of EVs was traced with PKH67 green fluorescent cell linker dye (PKH-67), and the signaling pathways involved in macrophage reprogramming were examined. ADMSC-EVs efficiently entered macrophages, promoted M2 polarization, suppressed inflammation, and improved survival rates in septic mice. Biodistribution studies demonstrated widespread organ accumulation, with notable localization in the lungs, liver, and kidneys. Mechanistically, the EV cargo miR-21-5p targeted Pellino E3 ubiquitin protein ligase 1 (PELI1), driving M2 polarization in vivo, which was accompanied by increased IL-10 levels. These findings position ADMSC-EVs as a viable cell-free therapeutic approach for mitigating LPS-induced sepsis through the delivery of miR-21-5p to PELI1, thereby supporting further development of EV-based immunomodulatory strategies for sepsis management
Advancing regenerative therapies with umbilical cord–derived mesenchymal stem cells: A review
Full text linkUmbilical cord–derived mesenchymal stem cells (UC-MSCs) are a clinically attractive regenerative and immunomodulatory platform that combines ethical accessibility, low immunogenicity, rapid expansion, genetic stability, and a potent paracrine secretome. This study aimed to synthesize evidence on safety, efficacy, and translational readiness by conducting a focused PubMed review (2014–2024) restricted to clinical studies and trials, using predefined inclusion and exclusion criteria and structured data extraction. Across indications, UC-MSCs show a consistent safety profile and signals of benefit mediated by tissue repair and immune regulation: in musculoskeletal disease they improve osteoarthritis pain and function and may slow osteonecrosis; in hepatology they sustain gains in decompensated cirrhosis, mitigate acute allograft rejection, and aid recovery from ischemic-type biliary lesions; as induction in renal transplantation they are feasible with early graft benefits; in type 2 diabetes responders improve glycemic control and inflammation, while maternal and obstetric factors can shape intrinsic cell properties; in neurology, studies in cerebral palsy, chronic spinal cord injury, and traumatic optic neuropathy report motor, sensory, and visual improvements; in COVID-19–related acute respiratory distress syndrome (ARDS) trials show better oxygenation, radiological recovery, quality of life, and modulation of the TNF–sTNFR2 axis; in immune-mediated and transplant settings they reduce graft-versus-host disease, with signals in systemic lupus erythematosus, refractory immune thrombocytopenia, Crohn’s fistulas, and as cotransplant support in aplastic anemia. The limitations of this study encompass small sample sizes, single-center designs, and short-duration trials. Additionally, there is significant heterogeneity concerning the source, manufacturing processes, dosage, administration routes, and endpoints. Other challenges include adherence to good manufacturing practices (GMP), issues related to potency, biobanking, logistical constraints, cost factors, and regulatory obstacles. Large multicenter randomized trials with standardized protocols and long-term follow-up, and combination strategies with biomaterials, gene engineering, and extracellular vesicle or exosome products, are needed to confirm durable benefit and enable routine clinical integration
HbA1c variability and risk of incident heart failure: A systematic review and meta-analysis
Full text linkVisit-to-visit variability in glycated hemoglobin (HbA1c) reflects long-term instability in glycemic control, potentially contributing to cardiovascular complications. However, the association between HbA1c variability and heart failure (HF) risk remains unclear. This meta-analysis aimed to quantify the relationship between HbA1c variability and the risk of incident HF in adults. A systematic search of PubMed, Embase, and Web of Science was conducted to identify relevant studies. Observational studies and post-hoc analyses of clinical trials evaluating the association between visit-to-visit HbA1c variability and incident HF were included. Random-effects models were employed to pool hazard ratios (HRs) with 95% confidence intervals (CIs), accounting for potential heterogeneity. A total of nine studies (n = 342,123) were included in the analysis. Overall, high HbA1c variability was associated with an increased risk of HF (pooled HR = 1.78, 95% CI: 1.39–2.27, p < 0.001; I² = 87%). Sensitivity analyses restricted to patients with type 2 diabetes (HR = 1.73, 95% CI: 1.35–2.22), high-quality studies (HR = 1.82, 95% CI: 1.32–2.50), or studies adjusting for mean HbA1c (HR = 1.68, 95% CI: 1.31–2.16) produced consistent results. Subgroup analyses indicated a stronger association in prospective cohorts (HR = 2.51) compared to retrospective or post-hoc studies (p for subgroup difference < 0.001). Meta-regression analysis revealed no significant modifying effects of age, sex, follow-up duration, or study quality (p all > 0.05). In conclusion, greater visit-to-visit HbA1c variability may be associated with an increased risk of incident HF, underscoring the prognostic importance of maintaining stable long-term glycemic control in patients with type 2 diabetes
HCAR score as a prognostic biomarker of survival in locally advanced nasopharyngeal carcinoma treated with concurrent chemoradiotherapy
Full text linkNasopharyngeal carcinoma (NPC) is an aggressive malignancy of the head and neck that is often diagnosed at a locally advanced stage (LANPC). In such cases, intensity-modulated radiotherapy combined with concurrent chemoradiotherapy (CCRT) is the standard treatment; however, the occurrence of distant metastasis and treatment failure remains prevalent. This study evaluates the prognostic significance of a novel composite score that combines hemoglobin levels and the C-reactive protein-to-albumin ratio (HCAR) in LANPC patients undergoing CCRT. We conducted a retrospective analysis of 233 LANPC patients treated with intensity-modulated radiotherapy and platinum-based CCRT from 2011 to 2020. Receiver operating characteristic curve analysis determined pretreatment hemoglobin (Hb) and C-reactive protein-to-albumin ratio (CAR) cut-offs of 11.0 g/dL and 3.0, respectively, which were utilized to create a three-tiered HCAR score: HCAR-0 (Hb ≥11.0 g/dL and CAR <3.0), HCAR-1 (Hb ≥11.0 g/dL and CAR ≥3.0 or Hb <11.0 g/dL and CAR <3.0), and HCAR-2 (Hb <11.0 g/dL and CAR ≥3.0). The primary endpoint of the study was overall survival (OS), while progression-free survival (PFS) was the secondary endpoint. With a median follow-up of 85.7 months, the median PFS and OS were 66.0 months and 108.0 months, respectively, with 5-year PFS and OS rates of 52.8% and 75.9%. The HCAR score significantly stratified patient outcomes: median PFS was not reached for HCAR-0, 66.0 months for HCAR-1, and 25.0 months for HCAR-2. Median OS also varied significantly, being not reached for HCAR-0, 108.0 months for HCAR-1, and 55.0 months for HCAR-2 (all p < 0.001). Corresponding 10-year PFS rates were 50.2%, 34.4%, and 5.0%, while 10-year OS rates were 68.3%, 41.6%, and 11.1%. Multivariate analysis revealed that the HCAR score remained an independent predictor of both PFS and OS, alongside T and N stage. The HCAR score shows promising prognostic utility for predicting OS and PFS in LANPC; however, performance estimates may be overly optimistic due to the lack of internal validation
Second-generation antipsychotics – Cardiac ion channel modulation and QT interval disturbances: A review
Full text linkSecond-generation antipsychotics (SGAs) are frequently prescribed in psychiatry due to their efficacy and improved tolerability compared to first-generation agents. However, these medications are associated with significant cardiac adverse effects, particularly QT interval prolongation and torsades de pointes (TdP). This review aims to summarize the mechanisms by which SGAs affect cardiac ion channels and how these actions contribute to QT interval disturbances and increased arrhythmia risk. A narrative literature review was conducted using PubMed, Web of Science, and Google Scholar, without year restrictions, focusing on English-language experimental and clinical studies related to clozapine, olanzapine, risperidone, quetiapine, and ziprasidone. The findings indicate that all five SGAs inhibit the rapid delayed rectifier potassium current (IKr) mediated by the human ether-a-go-go-related gene (hERG) potassium channel. Notably, the observed variability in the ratio of half-maximal inhibitory concentration to maximum free plasma concentration (IC₅₀/Cmax,free) reflects its dependence on both the degree of hERG inhibition and the pharmacokinetic properties specific to each SGA. Additionally, several SGAs affect other potassium, sodium, and calcium currents, which may either mitigate or exacerbate the consequences of IKr inhibition. In conclusion, QT interval prolongation associated with SGAs is primarily driven by hERG potassium channel blockade, although the degree of this effect varies significantly among different agents. This variability highlights the necessity for electrocardiogram (ECG) monitoring and individualized cardiac risk assessments, especially for vulnerable patient populations
Acid ceramidase expression and biomarker potential in patients with locally advanced rectal cancer
Full text linkAcid ceramidase (AC), a pivotal enzyme in sphingolipid metabolism, has been associated with various cancers; however, its specific role in rectal cancer remains poorly understood. This study aimed to explore the clinical significance of AC gene and protein expression in rectal cancer. We analyzed the expression of ASAH1, BAX, and BCL2 through quantitative Real-Time PCR in paired tumor and non-tumor tissue samples obtained from patients with locally advanced rectal cancer (LARC) prior to neoadjuvant chemoradiotherapy. Additionally, serum AC levels and standard biochemical parameters were assessed. We further evaluated ASAH1 expression using RNA-seq data from publicly available TCGA-READ datasets accessed via the UCSC Xena Browser. Two approaches indicated a significant reduction in ASAH1 expression in tumor tissue (p=0.004 and p<0.001, respectively). Receiver operating characteristic curve analysis revealed a modest capacity for ASAH1 expression to differentiate between tumor and non-tumor tissue in LARC patients (AUC=0.652, p=0.042). No correlation was observed between ASAH1 expression and the BAX/BCL2 ratio in tumor tissue, nor with serum AC levels or the CRP-albumin-lymphocyte (CALLY) index. Conversely, serum AC levels exhibited a negative correlation with the BAX/BCL2 ratio (rs=−0.536, p=0.002, FDR-adjusted q=0.021). Furthermore, ASAH1 expression, AC levels, and the CALLY index were not linked to overall survival or treatment response. A key finding of this study is the inverse relationship between serum AC levels and the pro-apoptotic status of tumor tissue, suggesting that circulating AC may provide valuable insights into tumor apoptotic activity. Further large-scale studies are necessary to validate these preliminary findings and elucidate the biomarker potential of AC in rectal cancer
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