{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:11:14Z","timestamp":1777943474399,"version":"3.51.4"},"reference-count":38,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["OMICS: A Journal of Integrative Biology"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:p>\n                    Diabetic peripheral neuropathy (DPN) is a prevalent complication of type 2 diabetes that is typically diagnosed after irreversible nerve damage, largely due to the lack of molecular biomarkers that distinguish neuropathy-specific changes from general diabetic pathology. From an integrative biology perspective, the network-level molecular mechanisms underlying DPN remain incompletely defined. In this study, transcriptomic profiles from peripheral blood mononuclear cells of healthy controls, patients with type 2 diabetes, and patients with DPN were analyzed using a systems-level, network-based bioinformatics framework. Comparative analysis identified genes specifically associated with DPN, distinct from broader diabetic alterations. Protein\u2013protein interaction and network topology analyses prioritized key hub genes enriched in immune signaling, calcium transport, lipid metabolism, and inflammatory pathways implicated in neuronal dysfunction. Among these, Toll-like receptor 9 (\n                    <jats:italic toggle=\"yes\">TLR9<\/jats:italic>\n                    ) emerged as a prominent biomarker candidate, demonstrating high network centrality and strong diagnostic performance (area under the curve = 1.0).\n                    <jats:italic toggle=\"yes\">TLR9<\/jats:italic>\n                    was significantly upregulated in DPN and functionally linked to mitogen-activated protein kinase and nuclear factor kappa-light-chain-enhancer of activated B-cell signaling pathways, consistent with immune-mediated mechanisms of neuropathic injury. Collectively, these findings define a DPN-specific molecular network and support\n                    <jats:italic toggle=\"yes\">TLR9<\/jats:italic>\n                    as a biomarker candidate, providing a systems-level foundation for future experimental validation and translational research in diabetic neuropathy.\n                  <\/jats:p>","DOI":"10.1177\/15578100261422824","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T14:35:26Z","timestamp":1771252526000},"page":"203-210","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Transcriptomic Profiling Identifies\n                    <i>TLR9<\/i>\n                    as a Key Biomarker of Diabetic Peripheral Neuropathy"],"prefix":"10.1177","volume":"30","author":[{"given":"Alekhya","family":"Bandi","sequence":"first","affiliation":[{"name":"Molecular Motors Laboratory, School of Chemical &amp; Biotechnology, SASTRA Deemed University, Thanjavur, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishna Varshitha","family":"Maradihalli","sequence":"additional","affiliation":[{"name":"Molecular Motors Laboratory, School of Chemical &amp; Biotechnology, SASTRA Deemed University, Thanjavur, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samyuktha","family":"Sunkara","sequence":"additional","affiliation":[{"name":"Molecular Motors Laboratory, School of Chemical &amp; Biotechnology, SASTRA Deemed University, Thanjavur, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srimari","family":"Srikanth","sequence":"additional","affiliation":[{"name":"Molecular Motors Laboratory, School of Chemical &amp; Biotechnology, SASTRA Deemed University, Thanjavur, India."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0226-3600","authenticated-orcid":false,"given":"Venkatasubramanian","family":"Ulaganathan","sequence":"additional","affiliation":[{"name":"Molecular Motors Laboratory, School of Chemical &amp; Biotechnology, SASTRA Deemed University, Thanjavur, India."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2022.02.016"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_3_2_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(01)00297-2"},{"key":"e_1_3_2_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp101"},{"key":"e_1_3_2_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70065-0"},{"key":"e_1_3_2_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03142-z"},{"key":"e_1_3_2_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.1008203"},{"key":"e_1_3_2_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14477"},{"key":"e_1_3_2_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-8-S4-S11"},{"key":"e_1_3_2_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.1.207"},{"key":"e_1_3_2_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00329"},{"key":"e_1_3_2_13_1","doi-asserted-by":"publisher","DOI":"10.4097\/kja.21209"},{"key":"e_1_3_2_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.07.157"},{"key":"e_1_3_2_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw313"},{"key":"e_1_3_2_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-08100-8"},{"key":"e_1_3_2_17_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.902193"},{"key":"e_1_3_2_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_3_2_19_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0219720012310038"},{"key":"e_1_3_2_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.14748"},{"key":"e_1_3_2_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-019-0499-3"},{"key":"e_1_3_2_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-022-00960-5"},{"key":"e_1_3_2_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_2_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3257-18.2019"},{"key":"e_1_3_2_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-s1-s4"},{"key":"e_1_3_2_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13030589"},{"issue":"1","key":"e_1_3_2_27_1","first-page":"81","article-title":"Upregulation of TLR9 may contribute to activation of microglia and painful diabetic neuropathy via the p38 MAPK pathway in rats","volume":"37","author":"Niu Z","year":"2022","unstructured":"Niu Z, , Bao L, , Chen J. Upregulation of TLR9 may contribute to activation of microglia and painful diabetic neuropathy via the p38 MAPK pathway in rats. 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