Balkan Medical Journal最新文献

Background: Rheumatoid arthritis (RA) is a leading cause of disability worldwide. Although global assessments of RA have been reported, age-specific estimates focusing on middle-aged adults [middle-aged adults (MAA); 40-59 years] remain limited.

Aims: To quantify the global, regional, and temporal burden of RA among MAA from 1990 to 2021 and project age-standardized trends through 2050.

Study design: A population-based descriptive epidemiological study using Global Burden of Disease (GBD) 2021 estimates.

Methods: GBD 2021 data (1990-2021) were used to estimate age-standardized incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life-year rates (ASDR) per 100,000 population among MAA. Temporal trends were assessed using joinpoint regression and expressed as the average annual percentage change (AAPC). Projections to 2050 were generated using a Bayesian age-period-cohort model. Burden patterns were summarized across sociodemographic index quintiles and 21 GBD regions.

Results: In 2021, the global ASIR, ASPR, ASMR, and ASDR among MAA were 19.53, 368.73, 0.19, and 56.74 per 100,000 population, respectively. From 1990 to 2021, ASIR and ASPR increased (AAPC = 0.24% and 0.43%), ASMR decreased (AAPC = -1.70%), and ASDR showed minimal net change (AAPC = 0.05%). Substantial variation was observed across SDI quintiles and GBD regions; SDI was positively correlated with ASIR and ASPR and negatively correlated with ASMR. Projections to 2050 indicated an ASIR of 19.22, an ASPR of 367.47, an ASMR of 0.111, and an ASDR of 52.18 per 100,000, with widening credible intervals over time.

Conclusion: Between 1990 and 2021, the RA burden among MAA was characterized by increasing ASIR and ASPR, declining ASMR, and relatively stable ASDR. Projections suggest that ASIR and ASPR will remain near recent levels, whereas ASMR and ASDR will show lower median values over time.

Background: The functional role of circular ribonucleic acids in ankylosing spondylitis (AS) remains poorly understood. In our previous study, circ_0004496 and actin gamma 1 (ACTG1) were found to be upregulated in ossified tissues from patients with AS.

Aims: This study investigated the regulatory role of circ_0004496 in pathological bone formation through the miR-145/ACTG1 axis.

Study design: Combined in vitro and in vivo experimental study.

Methods: Tissue samples were obtained from 15 patients with AS and hip ankylosis and 15 control patients with femoral neck fractures. Quantitative real-time polymerase chain reaction was performed to measure circ_0004496 and miR-145 expression. Western blot analysis was used to determine the protein levels of alkaline phosphatase (ALP), osteocalcin (OCN), runt-related transcription factor 2 (Runx2), and ACTG1. Cell proliferation was evaluated using Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays. Osteogenic differentiation was assessed by measuring ALP activity and performing Alizarin Red S staining. Interactions among circ_0004496, miR-145, and ACTG1 were examined using RNA immunoprecipitation (RIP), RNA pull-down, dual-luciferase reporter, and fluorescence in situ hybridization (FISH) assays.

Results: Circ_0004496 and ACTG1 expression levels were significantly elevated in AS hip capsule tissues, whereas miR-145 expression was reduced. Overexpression of circ_0004496 in AS-derived fibroblasts enhanced cell proliferation, accelerated cell cycle progression, increased calcium deposition, and upregulated ALP, OCN, and Runx2 protein levels. Mechanistically, circ_0004496 functioned as a molecular sponge for miR-145, which directly targets ACTG1. These regulatory interactions were confirmed by dual-luciferase reporter, RIP, RNA pulldown, and FISH assays. In vivo, circ_0004496 overexpression was associated with sacroiliac joint fusion in proteoglycan-induced arthritis mice.

Conclusion: Circ_0004496 overexpression promotes pathological bone formation in AS by regulating the miR-145/ACTG1 axis both in vitro and in vivo.

Background: Bisphenol A (BPA), a widely used industrial chemical, is a well-known endocrine disruptor linked to testicular damage and impaired male reproductive function. Fucoxanthin (Fx), a marine carotenoid with potent antioxidant properties, has not been extensively studied for its potential to mitigate BPA-induced testicular injury.

Aims: This study evaluated the protective effects of Fx against BPA-induced testicular injury and explored the underlying signaling mechanisms.

Study design: Experimental study.

Methods: A mouse model of BPA-induced testicular injury was established. Transcriptomic analysis was performed to identify significantly altered genes. The therapeutic potential of Fx was assessed using combined molecular and histological approaches. Complementary in vitro experiments with TM3 Leydig cells were conducted to support the in vitro findings.

Results: Fx administration markedly attenuated BPA-induced disruptions in serum sex hormones, testicular histopathology, and proinflammatory cytokine levels. Ribonucleic acid sequencing revealed that Fx's protective effects are associated with modulation of the nuclear factor kappa B (NF-κB), nucleotide-binding oligomerization domain-like, and Toll-like receptor signaling pathways. Validation experiments indicated that Fx inhibits nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation and suppresses pyroptosis, accompanied by downregulation of key genes and proteins in the lipopolysaccharide/NLRP3 signaling cascade. In vitro analyses confirmed that Fx reduces oxidative stress and inflammation by inhibiting NF-κB activation and pyroptosis.

Conclusion: These findings suggest that Fx may serve as a promising dietary supplement or nutraceutical agent to mitigate the adverse reproductive effects of environmental endocrine disruptors, with potential benefits for male reproductive health.

Background: Epithelial–mesenchymal transition and cancer cell stemness (CSC) are critical processes that driving the invasion and lethality of lung adenocarcinoma (LUAD). The chromatin remodeler ARID4B has been implicated in other cancers; however, its specific role and underlying mechanism in LUAD progression remain unclear.

Aims: To elucidate the function of ARID4B in LUAD.

Study design: This study integrated bioinformatics analysis, in vitro cellular functional assays, and in vivo orthotopic lung cancer models to investigate the oncogenic role of ARID4B.

Methods: ARID4B expression and its correlation with patient prognosis were analyzed using public databases. ARID4B was silenced using two independent short hairpin RNAs in A549 and H1650 LUAD cell lines, and subsequent changes in invasion, migration, and stemness markers were assessed. Tumor metastasis was evaluated using orthotopic and tail-vein injection mouse models. The regulatory mechanism by which ARID4B controls GPRC5C expression was investigated using dual-luciferase reporter and chromatin immunoprecipitation assays.

Results: ARID4B was significantly upregulated in LUAD and was associated with poor patient prognosis. Silencing ARID4B in LUAD cells significantly reduced their invasion and migration capabilities (adj. p < 0.01). Furthermore, ARID4B knockdown resulted in downregulation of SNAIL, upregulation of E-cadherin, and impairment of stem-like characteristics, as demonstrated by decreased CSC marker expression and reduced sphere-forming ability (adj. p < 0.05). In the orthotopic model, ARID4B deficiency markedly inhibited tumor metastasis (adj. p < 0.001). Mechanistically, ARID4B transcriptionally activated GPRC5C (adj. p < 0.01). Furthermore, ARID4B knockdown increased histone H1 occupancy at the GPRC5C promoter (adj. p < 0.01), indicating that ARID4B facilitates an open chromatin state. Rescue experiments further confirmed that GPRC5C is required for ARID4B-mediated maintenance of tumor invasiveness and cancer stemness.

Conclusion: ARID4B promotes LUAD malignancy by transcriptionally activating GPRC5C, thereby driving EMT and cancer stemness.

Background: Childhood interstitial lung diseases (chILD) and immunodeficiencies are rare, heterogeneous, and clinically challenging disorders.

Aims: To evaluate the clinical and radiological characteristics of immunodeficiency-related chILD using data from the Türkiye chILD Registry (chILD-TR).

Study design: Retrospective cohort study.

Methods: Patients registered with the B3 code, according to the chILD-European classification, from 18 participating centers were included. Patients were classified into primary immunodeficiency (PID) and secondary immunodeficiency (SID) groups. Demographic, clinical, and radiological variables were compared between the two groups.

Results: Among 667 patients registered in the chILD-TR, 114 (17%) had immunodeficiency-related chILD, including 53 (47%) females. The median current age was 156 months (range: 23-357), the age at symptom onset was 60 months (range: 0-215), and the age at chILD diagnosis was 85 months (range: 2-217). PID was identified in 77 patients (67.6%) and SID in 37 patients (32.4%). The PID group had significantly lower median current age, age at first symptom, and age at chILD diagnosis compared with the SID group (p < 0.05). No significant differences were observed in growth z-scores between the groups (p > 0.05). A history of hematopoietic stem cell transplantation (HSCT) and a diagnosis of bronchiolitis obliterans (BO) were more frequent in the SID group (p < 0.05). The most common computed tomography findings were ground-glass opacities in PID and mosaic perfusion in SID. During follow-up, 14 patients (12.3%) died.

Conclusion: Immunodeficiency-associated chILD encompasses a heterogeneous spectrum of disorders and is associated with increased mortality. Distinct clinical and radiological patterns were observed between PID and SID. These findings underscore the importance of early detection, individualized diagnostic strategies, and ongoing follow-up to improve outcomes in this high-risk population. Recognition of post-infectious BO and following HSCT is critical for timely intervention.

Background: Cesarean section is frequently performed for breech presentation; however, external cephalic version (ECV) is recommended as an alternative strategy to increase the likelihood of vaginal birth. Tocolytic agents are commonly administrated to improve ECV success, yet the comparative effectiveness of different regimens remains inadequately characterized.

Aims: To systematically evaluate and compare the efficacy and safety of various tocolytic agents in facilitating successful ECV through a Bayesian network meta-analysis.

Study design: Bayesian network meta-analysis.

Methods: Bayesian network meta-analysis was performed using the "gemtc" package in R 4.1.1. Treatment effects were quantified by calculating odds ratios (ORs) with corresponding 95% credible intervals (CrIs). Surface under the cumulative ranking curve values were used to rank tocolytic agents according to ECV success rates, maternal outcomes, and adverse events.

Results: A total of sixteen RCTs encompassing 2,817 participants and six distinct tocolytic agents met the inclusion criteria. Compared with placebo, terbutaline (OR: 2.7, 95% CrI: 1.1-6.4) and ritodrine (OR: 2.2, 95% CrI: 1.4-3.9) were associated with significantly higher ECV success rates. Additionally, terbutaline was linked to an increased likelihood of vaginal delivery (OR: 2.0, 95% CrI: 1.0-2.9). Maternal adverse effects, including tachycardia, palpitations, hypotension, nausea, dizziness, and flushing, were more frequently reported with terbutaline, nifedipine, and nitroglycerin than with placebo. No statistically significant differences in fetal heart rate abnormalities were detected among the elevated interventions.

Conclusion: Terbutaline and ritodrine appear to offer superior efficacy in improving ECV success compared with alternative tocolytic agents, albeit with a higher incidence of maternal side effects. Consequently, clinical decision-making regarding tocolytic use should be informed by a comprehensive assessment of the associated benefits and potential risks.

Background: The fetal liver is perfused by the umbilical vein (UV) and the main portal vein (MPV), both of which are crucial for nutrient delivery. The configuration of the umbilicoportal anastomosis may influence MPV blood flow and potentially affect fetal liver perfusion in fetuses with fetal growth restriction (FGR).

Aims: To evaluate absolute and normalized UV and MPV blood flows in fetuses with normal growth and FGR, and to investigate the effect of umbilicoportal anastomosis type on MPV flow.

Study design: Prospective case–control study.

Methods: Ultrasound was used to measure UV and MPV diameters, while Doppler ultrasound assessed time-averaged maximum velocities. Flow volumes were calculated as time-averaged maximum velocity volume and normalized to estimated fetal weight (TAMXVVN) and abdominal circumference. Anastomoses were categorized as T-, X-, or H-shaped. Z-scores were derived from AGA nomograms.

Results: Compared with AGA fetuses, FGR fetuses exhibited significantly smaller UV diameters, lower absolute UV flow, UV-TAMXVVN, and UVTAMXVV/ AC (p < 0.05), but higher MPV-TAMXVVN (p < 0.05), suggesting compensatory redistribution. Both UV and MPV flows showed strong correlations with gestational age (r > 0.7, p < 0.001). UV-TAMXVVN Z-scores decreased with gestation, whereas MPV-TAMXVVN Z-scores increased until 32 weeks before plateauing. Blood flow parameters did not differ significantly across anastomosis types in either group.

Conclusion: FGR fetuses demonstrate reduced UV perfusion with compensatory increases in MPV flow. The type of umbilicoportal anastomosis does not significantly affect MPV blood flow.