Balkan Medical JournalPub Date : 2026-04-30Epub Date: 2026-03-10DOI: 10.4274/balkanmedj.galenos.2026.2025-12-249
Yu-Cong Zou, Yong-Sheng Wu, Ting Hu, Hao-Bin Zeng
{"title":"Overexpression of Circ_0004496 is Associated with Pathological Bone Formation in Ankylosing Spondylitis via the miR-145/ACTG1 Axis.","authors":"Yu-Cong Zou, Yong-Sheng Wu, Ting Hu, Hao-Bin Zeng","doi":"10.4274/balkanmedj.galenos.2026.2025-12-249","DOIUrl":"10.4274/balkanmedj.galenos.2026.2025-12-249","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Aims: </strong>To investiagate the regulatory role of circ_0004496 in pathological bone formation through the miR-145/ACTG1 axis.</p><p><strong>Study design: </strong>Combined <i>in vitro</i> and <i>in vivo</i> experimental study.</p><p><strong>Methods: </strong>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 <i>in situ</i> hybridization (FISH) assays.</p><p><strong>Results: </strong>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. <i>In vivo</i>, circ_0004496 overexpression was associated with sacroiliac joint fusion in proteoglycan-induced arthritis mice.</p><p><strong>Conclusion: </strong>Circ_0004496 overexpression promotes pathological bone formation in AS by regulating the miR-145/ACTG1 axis both <i>in vitro</i> and <i>in vivo</i>.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"267-280"},"PeriodicalIF":3.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fucoxanthin Attenuates Bisphenol A-Induced Testicular Injury via NF-κB-Mediated Pyroptosis Inhibition.","authors":"Ke Xu, Xiangyu Ren, Hongjie Cao, Tiantian Lyu, Zuisu Yang, Fangfang Huang","doi":"10.4274/balkanmedj.galenos.2026.2025-11-268","DOIUrl":"10.4274/balkanmedj.galenos.2026.2025-11-268","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Aims: </strong>To evaluate the protective effects of Fx against BPA-induced testicular injury and explored the underlying signaling mechanisms.</p><p><strong>Study design: </strong>Experimental study.</p><p><strong>Methods: </strong>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 <i>in vitro</i> experiments with TM3 Leydig cells were conducted to support the <i>in vitro</i> findings.</p><p><strong>Results: </strong>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. <i>In vitro</i> analyses confirmed that Fx reduces oxidative stress and inflammation by inhibiting NF-κB activation and pyroptosis.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"253-266"},"PeriodicalIF":3.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147363972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Balkan Medical JournalPub Date : 2026-04-30Epub Date: 2026-01-08DOI: 10.4274/balkanmedj.galenos.2025.2025-10-197
Ning Zhao, Li Yang, Ting Li
{"title":"Thymopentin-Induced Myasthenia Gravis: A Case Report Highlighting Clinical Vigilance.","authors":"Ning Zhao, Li Yang, Ting Li","doi":"10.4274/balkanmedj.galenos.2025.2025-10-197","DOIUrl":"10.4274/balkanmedj.galenos.2025.2025-10-197","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"291-293"},"PeriodicalIF":3.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Balkan Medical JournalPub Date : 2026-04-30DOI: 10.4274/balkanmedj.galenos.2026.2026-1-289
Ivana Maleva Kostovska, Sanja Kiprijanovska, Predrag Noveski, Marija Vujovikj, Marija Terzic, Dijana Plaseska-Karanfilska
{"title":"<i>ATM</i> Variants and Breast Cancer Risk in North Macedonia: Focus on the Regionally Enriched <i>p.(Leu2492Arg)</i> Variant.","authors":"Ivana Maleva Kostovska, Sanja Kiprijanovska, Predrag Noveski, Marija Vujovikj, Marija Terzic, Dijana Plaseska-Karanfilska","doi":"10.4274/balkanmedj.galenos.2026.2026-1-289","DOIUrl":"https://doi.org/10.4274/balkanmedj.galenos.2026.2026-1-289","url":null,"abstract":"<p><strong>Background: </strong>Germline pathogenic variants (PVs) in the ataxia-telangiectasia mutated (<i>ATM</i>) gene are established moderate-risk factors for breast cancer (BC), however, population-specific variant spectra and the clinical significance of many missense variants remain incompletely characterized.</p><p><strong>Aims: </strong>To evaluate the prevalence of <i>ATM</i> variants in a large cohort of patients with BC from North Macedonia and compare it with that in the general population, with a particular focus on the frequency of the p.(Leu2492Arg) variant and its distribution relative to global genomic datasets.</p><p><strong>Study design: </strong>This study was conducted as a retrospective case-control analysis.</p><p><strong>Methods: </strong><i>ATM</i> variants were analyzed in 1,211 patients with BC from North Macedonia using a targeted hereditary cancer gene panel. These findings were compared with those from 1,303 population-based controls analyzed by clinical exome or whole-exome sequencing.</p><p><strong>Results: </strong>Pathogenic <i>ATM</i> variants were identified in 1.9% of BC cases and 0.4% of controls, indicating a significantly increased risk of BC [odds ratio (OR) = 5.02, <i>p</i> = 0.0006]. Most PVs were protein-truncating, with six recurrent variants accounting for over 70% of detections, suggesting regional enrichment. Carriers showed a significantly higher prevalence of human epidermal growth factor receptor 2-positive tumors (OR = 2.92, <i>p</i> = 0.0189). Variants of uncertain significance were observed at comparable frequencies in cases and controls. The p.(Leu2492Arg) missense variant was more frequently detected in cases than in controls (1.9% vs. 1.1%; OR = 1.78, <i>p</i> = 0.086) and exhibited a markedly higher allele frequency in this population than in global databases.</p><p><strong>Conclusion: </strong>These findings confirm <i>ATM</i> as a clinically relevant BC susceptibility gene in North Macedonia and highlight the population-specific enrichment of both PVs and the p.(Leu2492Arg) missense variant. The results emphasize the importance of using population-matched controls and regional genomic data for accurate risk assessment and variant interpretation.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Balkan Medical JournalPub Date : 2026-04-30Epub Date: 2025-12-22DOI: 10.4274/balkanmedj.galenos.2025.2025-11-168
Yusuf Kavuzlu, Serdar Solak, Zafer Koçak
{"title":"Treatment of Steroid-Resistant Radiation-Induced Cerebral Edema with <i>Boswellia serrata</i>.","authors":"Yusuf Kavuzlu, Serdar Solak, Zafer Koçak","doi":"10.4274/balkanmedj.galenos.2025.2025-11-168","DOIUrl":"10.4274/balkanmedj.galenos.2025.2025-11-168","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"288-290"},"PeriodicalIF":3.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Balkan Medical JournalPub Date : 2026-04-30DOI: 10.4274/balkanmedj.galenos.2026.2026.270326
Yeşim Hülya Uz, Suat Erdoğan
{"title":"Enhancing the Therapeutic Index of Bioactive Compounds Through Novel Delivery Systems.","authors":"Yeşim Hülya Uz, Suat Erdoğan","doi":"10.4274/balkanmedj.galenos.2026.2026.270326","DOIUrl":"10.4274/balkanmedj.galenos.2026.2026.270326","url":null,"abstract":"","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":"43 5","pages":"227-229"},"PeriodicalIF":3.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Balkan Medical JournalPub Date : 2026-04-30DOI: 10.4274/balkanmedj.galenos.2026.2026-3-145
Esra Eraslan Aydemir, Feride Özkara Akkuş, Murat Faik Erdoğan
{"title":"Anti-Thyroglobulin Antibodies as a Surrogate Tumor Marker for the Follow-Up of the Differentiated Thyroid Carcinoma: Clinical Implications and Pitfalls.","authors":"Esra Eraslan Aydemir, Feride Özkara Akkuş, Murat Faik Erdoğan","doi":"10.4274/balkanmedj.galenos.2026.2026-3-145","DOIUrl":"10.4274/balkanmedj.galenos.2026.2026-3-145","url":null,"abstract":"<p><p>Antithyroglobulin antibodies (TgAb) are present in 10-25% of patients with differentiated thyroid cancer (DTC) and significantly affect the reliability of serum thyroglobulin (Tg) measurements during follow-up. Beyond causing assay interference, TgAb have emerged as independent surrogate tumor markers with prognostic implications. This review summarizes the current evidence on antithyroglobulin antibody biology, measurement methodologies, interference dynamics, and clinical utility as surrogate tumor markers in DTC surveillance. A narrative synthesis of the relevant English-language literature was performed, focusing on key clinical studies and recent guidelines. TgAb can lead to the underestimation of Tg levels in immunometric assays, potentially masking residual disease. Trend monitoring, rather than absolute antithyroglobulin antibody values, provides superior prognostic information; declining trends indicate favorable outcomes, whereas rising trends are associated with disease persistence or recurrence. <i>De novo</i> antithyroglobulin antibody positivity does not appear to serve as an early biomarker of recurrence. In antithyroglobulin antibody-positive patients, imaging-based surveillance, particularly neck ultrasonography, remains the cornerstone of follow-up. In conclusion, TgAb act as both interferents and surrogate tumor markers in DTC surveillance, and the integrated use of antithyroglobulin antibody trends and imaging is necessary for the optimal management of antithyroglobulin antibody-positive patients.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":"43 5","pages":"230-237"},"PeriodicalIF":3.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}