{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T07:05:10Z","timestamp":1784531110171,"version":"3.55.0"},"reference-count":63,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Internal Grant of \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara (Projects for Experienced Researchers of \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara\u2014Project Nr. 6 EXP\/2020)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetic kidney disease (DKD) displays a high prevalence of cardiovascular and cerebrovascular disease. Both the kidney and the brain share common pathogenic mechanisms, such as inflammation, endothelial dysfunction, oxidative stress, and mitochondrial dysfunction. The aim of this study was to establish a potential association of cerebral vessel remodeling and its related functional impairment with biomarkers of inflammation, oxidative stress, and mitochondrial dysfunction in the early stages of DKD in type 2 diabetes mellitus (DM) patients. A cohort of 184 patients and 39 healthy controls was assessed concerning serum and urinary stromal cell-derived factor-1 (SDF-1), P-selectin, advanced oxidation protein products (AOPPs), urinary synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), and N-acetyl-\u03b2-(D)-glucosaminidase (NAG). The quantification of the mitochondrial DNA copy number (mtDNA-CN) and nuclear DNA (nDNA) in urine and peripheral blood was conducted using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Using TaqMan tests, the beta-2 microglobulin nuclear gene (B2M) and the cytochrome b (CYTB) gene, which encodes subunit 2 of NADH dehydrogenase (ND2), were evaluated. The MtDNA-CN is the ratio of mitochondrial DNA to nuclear DNA copies, ascertained through the examination of the CYTB\/B2M and ND2\/B2M ratios. The intima-media thickness (IMT) measurements of the common carotid arteries (CCAs), along with the pulsatility index (PI) and resistivity index (RI) of the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), were obtained through cerebral Doppler ultrasonography (US). Additionally, the breath-holding index (BHI) was also measured by cerebral Doppler US. PI-ICAs, PI-MCAs, CCAs-IMT, RI-MCAs, and RI-ICAs demonstrated direct relationships with SDF-1, P-selectin, AOPPs, urine mtDNA, podocalyxin, synaptopodin, NAG, and KIM-1 while showing indirect correlations with serum mtDNA and the eGFR. In contrast, the BHI had negative correlations with SDF-1, P-selectin, AOPPs, urine mtDNA, synaptopodin, podocalyxin, KIM-1, and NAG while showing direct associations with serum mtDNA and the eGFR. In conclusion, a causative association exists among SDF-1, P-selectin, and AOPPs, as well as mitochondrial dysfunction, in early diabetic kidney disease (DKD) and significant cerebrovascular alterations in patients with type 2 diabetes mellitus and normoalbuminuric DKD, with no neurological symptoms.<\/jats:p>","DOI":"10.3390\/ijms26104481","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T06:47:15Z","timestamp":1746686835000},"page":"4481","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Stromal Cell-Derived Factor-1, P-Selectin, and Advanced Oxidation Protein Products with Mitochondrial Dysfunction Concurrently Impact Cerebral Vessels in Patients with Normoalbuminuric Diabetic Kidney Disease and Type 2 Diabetes Mellitus"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3138-3051","authenticated-orcid":false,"given":"Ligia","family":"Petrica","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine II, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Centre for Cognitive Research in Neuropsychiatric Pathology (Neuropsy-Cog), Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Center for Translational Research and Systems Medicine, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"County Emergency Hospital Timisoara, 300723 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florica","family":"Gadalean","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine II, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"County Emergency Hospital Timisoara, 300723 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1824-2628","authenticated-orcid":false,"given":"Adrian","family":"Vlad","sequence":"additional","affiliation":[{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Centre for Cognitive Research in Neuropsychiatric Pathology (Neuropsy-Cog), Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Center for Translational Research and Systems Medicine, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"County Emergency Hospital Timisoara, 300723 Timisoara, Romania"},{"name":"Division of Diabetes, Nutrition, and Metabolic Diseases, Department of Internal Medicine II, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danina Mirela","family":"Muntean","sequence":"additional","affiliation":[{"name":"Centre for 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Romania"},{"name":"Division of Pharmacology, Department of Biochemistry and Pharmacology IV, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Dumitrascu","sequence":"additional","affiliation":[{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"County Emergency Hospital Timisoara, 300723 Timisoara, Romania"},{"name":"Division of Pharmacology, Department of Biochemistry and Pharmacology IV, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flaviu","family":"Bob","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of 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Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"County Emergency Hospital Timisoara, 300723 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9215-5154","authenticated-orcid":false,"given":"Sorin","family":"Ursoniu","sequence":"additional","affiliation":[{"name":"Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Centre for Cognitive Research in Neuropsychiatric Pathology (Neuropsy-Cog), Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Center for Translational Research and Systems Medicine, Faculty of Medicine, \u201cVictor Babes\u201d University of 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University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"Centre for Cognitive Research in Neuropsychiatric Pathology (Neuropsy-Cog), Faculty of Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"},{"name":"County Emergency Hospital Timisoara, 300723 Timisoara, Romania"},{"name":"Division of Neurology I, Department of Neurosciences VIII, \u201cVictor Babes\u201d University of Medicine and Pharmacy, No. 2, Eftimie Murgu Sq., 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.mcna.2023.03.004","article-title":"Diabetic kidney disease: An update","volume":"107","author":"Gupta","year":"2023","journal-title":"Med. 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