{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T19:56:40Z","timestamp":1780084600371,"version":"3.54.0"},"reference-count":33,"publisher":"Pensoft Publishers","issue":"6","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["FM"],"abstract":"<jats:p>\n                    \ufeff\n                    <jats:bold>Abstract<\/jats:bold>\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Introduction<\/jats:bold>\n                    : Varicocele, characterized by the enlargement of scrotal veins, is a common contributor to male infertility, but its genetic underpinnings remain largely unknown.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Aim<\/jats:bold>\n                    : The goal of this study is to identify potential biomarkers associated with varicocele in order to better understand its molecular mechanisms.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Materials and methods<\/jats:bold>\n                    : Using the three primary databases, NCBI, DisGeNET, and OpenTarget, we analyzed gene variants and found 79 pertinent genes associated with varicocele. Protein-protein interaction analysis was performed using STRING and visualized with Cytoscape. Molecular Complex Detection (MCODE) and CytoHubba tools helped identify significant protein clusters.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    : The gene ontology analysis shows that there are 79 proteins involved in the inflammatory process, the regulation of gene expression, and cellular components that play a role in oxidative stress and angiogenesis. Our results revealed three key biomarkers: Interleukin-1 beta (IL1B), B-cell lymphoma 2 (BCL2), and matrix metalloproteinase-9 (MMP-9). These proteins are involved in critical processes, such as inflammation, oxidative stress, angiogenesis, and vascular damage, that are central to the pathophysiology of varicocele.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion<\/jats:bold>\n                    : The identification of IL1B, BCL2, and MMP-9 offers new insights into varicocele\u2019s molecular mechanisms and suggests potential targets for diagnostic and therapeutic strategies, advancing personalized treatment approaches for fertility restoration.\n                  <\/jats:p>","DOI":"10.3897\/folmed.67.e168906","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:40:26Z","timestamp":1766050826000},"source":"Crossref","is-referenced-by-count":1,"title":["Identifying potential novel biomarkers for varicocele: A bioinformatics approach to genomics analysis"],"prefix":"10.3897","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5301-0854","authenticated-orcid":true,"given":"Muhammad","family":"Farid","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Ahmad Dahlan University, Yogyakarta, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanin Fitri","family":"Aqilanisa","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Ahmad Dahlan University, Yogyakarta, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2258","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"168906_B1","unstructured":"1. 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Cannarella R, Shah R, Hamoda TA, et al. Does varicocele repair improve conventional semen parameters? A meta-analytic study of before-after data. World J Mens Health 2023; 42(1):92.","DOI":"10.5534\/wjmh.230034"},{"key":"168906_B6","unstructured":"6. Esfahani MHN, Tavalaee M. Origin and role of DNA damage in varicocele. Int J Fertil Steril 2012; 6(3):141\u20136. PMCID: PMC3850301."},{"key":"168906_B7","doi-asserted-by":"crossref","unstructured":"7. Brannigan RE. Introduction: varicoceles: a contemporary perspective. Fertil Steril 2017; 108(3):361\u20133.","DOI":"10.1016\/j.fertnstert.2017.07.1161"},{"key":"168906_B8","unstructured":"8. Biyani CS, Cartledge J, Janetschek G. Varicocele. Clin Evid [Internet] 2008; Available from: www.clinicalevidence.com"},{"key":"168906_B9","doi-asserted-by":"crossref","unstructured":"9. Tanrikut C, Goldstein M, Rosoff JS, et al. Varicocele as a risk factor for androgen deficiency and effect of repair. BJU Int 2011; 108(9):1480\u20134.","DOI":"10.1111\/j.1464-410X.2010.10030.x"},{"key":"168906_B10","doi-asserted-by":"crossref","unstructured":"10. Shridharani A, Owen RC, Elkelany OO, et al. The significance of clinical practice guidelines on adult varicocele detection and management. Asian J Androl 2016; 18(2):269\u201375.","DOI":"10.4103\/1008-682X.172641"},{"key":"168906_B11","unstructured":"11. Heidari MM, Khatami M, Talebi AR, et al. Mutation analysis of TNP1 gene in infertile men with varicocele. Iran J Reprod Med 2014; 12(4):236."},{"key":"168906_B12","doi-asserted-by":"crossref","unstructured":"12. Raman JD, Walmsley K, Goldstein M. Inheritance of varicoceles. Urology 2005; 65(6):1186\u20139.","DOI":"10.1016\/j.urology.2004.12.057"},{"key":"168906_B13","doi-asserted-by":"crossref","unstructured":"13. Mokhtari G, Pourreza F, Falahatkar S, et al. Comparison of prevalence of varicocele in first-degree relatives of patients with varicocele and male kidney donors. Urology 2008; 71(4):666\u20138.","DOI":"10.1016\/j.urology.2007.11.116"},{"key":"168906_B14","doi-asserted-by":"crossref","unstructured":"14. Kahraman CY, Tasdemir S, Sahin I, et al. The relationship between endothelial nitric oxide synthase gene (NOS3) polymorphisms, NOS3 expression, and varicocele. Genet Test Mol Biomarkers 2016; 20(4):191\u20136.","DOI":"10.1089\/gtmb.2015.0294"},{"key":"168906_B15","doi-asserted-by":"crossref","unstructured":"15. Lecouter J, Lin R, Tejada M, et al. The endocrine-gland-derived VEGF homologue Bv8 promotes angiogenesis in the testis: Localization of Bv8 receptors to endothelial cells. Proc Natl Acad Sci USA [Internet] 2003; Available from: www.pnas.org","DOI":"10.1073\/pnas.0337667100"},{"key":"168906_B16","doi-asserted-by":"crossref","unstructured":"16. Santana VP, Miranda-Furtado CL, de Oliveira-Gennaro FG, et al. Genetics and epigenetics of varicocele pathophysiology: an overview. J Assist Reprod Genet 2017; 34(7):839\u201347.","DOI":"10.1007\/s10815-017-0931-5"},{"key":"168906_B17","doi-asserted-by":"crossref","unstructured":"17. Chiba K, Ramasamy R, Lamb DJ, et al. The varicocele: Diagnostic dilemmas, therapeutic challenges and future perspectives. Asian J Androl 2016; 18(2):276\u201381.","DOI":"10.4103\/1008-682X.167724"},{"key":"168906_B18","doi-asserted-by":"crossref","unstructured":"18. Selvam MKP, Samanta L, Agarwal A. Functional analysis of differentially expressed acetylated spermatozoal proteins in infertile men with unilateral and bilateral varicocele. Int J Mol Sci 2020; 21(9).","DOI":"10.3390\/ijms21093155"},{"key":"168906_B19","doi-asserted-by":"crossref","unstructured":"19. Zhu J, Ou N, Song Y, et al. Identification and verification of key genes in varicocele rats through high-throughput sequencing and bioinformatics analysis. Andrologia 2020; 52(9).","DOI":"10.1111\/and.13662"},{"key":"168906_B20","unstructured":"20. Nasr-Esfahani A, Valipour Motlagh A, Adib M, et al. Integrative bioinformatics analysis of the cell division cycle and ribosomal pathways in the rat varicocele: implications for drug discovery. Cell J 2023; 25(10):727\u201337."},{"key":"168906_B21","doi-asserted-by":"publisher","DOI":"10.1186\/s43042-024-00512-7"},{"key":"168906_B22","doi-asserted-by":"publisher","DOI":"10.1186\/s43042-024-00528-z"},{"key":"168906_B23","doi-asserted-by":"crossref","unstructured":"23. Shen J, Zhao M, Zhang C, et al. IL-1\u03b2 in atherosclerotic vascular calcification: From bench to bedside. Int J Biol Sci 2021; 17(15):4353\u201364.","DOI":"10.7150\/ijbs.66537"},{"key":"168906_B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01426\/full"},{"key":"168906_B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110309"},{"key":"168906_B26","doi-asserted-by":"crossref","unstructured":"26. Dinarello CA. A clinical perspective of IL-1\u03b2 as the gatekeeper of inflammation. Eur J Immunol 2011; 41(5):1203\u201317.","DOI":"10.1002\/eji.201141550"},{"key":"168906_B27","doi-asserted-by":"crossref","unstructured":"27. Lee JD, Jeng SY, Lee TH. Bcl-2 overexpression in the internal spermatic vein of patients with varicocele. J Formos Med Assoc 2007; 106(4):308\u201312.","DOI":"10.1016\/S0929-6646(09)60257-6"},{"key":"168906_B28","doi-asserted-by":"crossref","unstructured":"28. Mostafa T, Rashed L, Nabil N, et al. Seminal BAX and BCL2 gene and protein expressions in infertile men with varicocele. Urology 2014; 84(3):590\u20135.","DOI":"10.1016\/j.urology.2014.05.016"},{"key":"168906_B29","doi-asserted-by":"crossref","unstructured":"29. Lee JD, Yang WK, Lee TH. Increased expression of hypoxia-inducible factor-1 alpha and Bcl-2 in varicocele and varicose veins. Ann Vasc Surg 2012; 26(8):1100\u20135.","DOI":"10.1016\/j.avsg.2011.12.014"},{"key":"168906_B30","doi-asserted-by":"crossref","unstructured":"30. Zhu SM, Rao T, Yang X, et al. Autophagy may play an important role in varicocele. Mol Med Rep 2017; 16(4):5471\u20139.","DOI":"10.3892\/mmr.2017.7253"},{"key":"168906_B31","doi-asserted-by":"crossref","unstructured":"31. Mazuchov\u00e1 J, Hala\u0161ov\u00e1 E, Mazuch J, et al. Investigation of association between genetic polymorphisms of MMP2, MMP8, MMP9 and TIMP2 and development of varicose veins in the Slovak population \u2013 pilot study. Physiol Res 2021; 69(Supplement 3):S443\u201354.","DOI":"10.33549\/physiolres.934597"},{"key":"168906_B32","doi-asserted-by":"crossref","unstructured":"32. Serra R, Buffone G, Costanzo G, et al. Altered metalloproteinase-9 expression as least common denominator between varicocele, inguinal hernia, and chronic venous disorders. Ann Vasc Surg 2014; 28(3):705\u20139.","DOI":"10.1016\/j.avsg.2013.07.026"},{"key":"168906_B33","doi-asserted-by":"crossref","unstructured":"33. Omar SS, Mahfouz W, Dawood W, et al. Relation of nitric oxide synthase gene (NOS3) polymorphisms to varicocele risk and post-varicocelectomy seminal oxidative stress reduction. 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