{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:02:39Z","timestamp":1790740959303,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp; Function"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Disturbances in one\u2010carbon metabolism, endothelial signaling, oxidative stress, and coagulation balance are central features of diabetes\u2010associated microvascular disease, and targeted micronutrient supplementation\u2014including\n                    <jats:sc>L<\/jats:sc>\n                    \u2010methylfolate, methylcobalamin, pyridoxal\u20105\u2032\u2010phosphate, antioxidants, and thiol donors\u2014may modulate homocysteine remethylation, endothelial function, and angiogenic signaling. In a 6\u2010month pilot study of ten patients with type 2 diabetes, mild diabetic retinopathy, and MTHFR polymorphisms, micronutrient supplementation was associated with a 23% reduction in serum homocysteine, a 47% decrease in plasma VEGF, and a 15% increase in\n                    <jats:sc>D<\/jats:sc>\n                    \u2010dimer, biomarker shifts that are mechanistically consistent with modulation of homocysteine metabolism, oxidative stress, endothelial signaling, and fibrin turnover. Interpretation of these findings is limited by the small sample size, absence of a control group, lack of functional vascular or imaging endpoints, and incomplete coagulation assessment, as\n                    <jats:sc>D<\/jats:sc>\n                    \u2010dimer elevations alone cannot distinguish enhanced fibrin clearance from increased thrombotic risk. While homocysteine\u2010lowering effects were biochemically evident, they should be contextualized within prior large\u2010scale trials demonstrating discordance between total homocysteine reduction and cardiovascular outcomes, and consideration of downstream metabolites, such as homocysteine\u2010thiolactone, N\u2010homocysteinylated proteins, and S\u2010adenosylhomocysteine, may provide additional mechanistic insight. Collectively, these findings are hypothesis\u2010generating, reflecting biochemical engagement of relevant vascular pathways rather than confirmed clinical benefit, and underscore the need for future randomized, genotype\u2010stratified studies incorporating serial biomarker and functional assessments to establish the physiological and therapeutic relevance of targeted micronutrient interventions in diabetic microvascular disease.\n                  <\/jats:p>","DOI":"10.1002\/cbf.70243","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T07:49:21Z","timestamp":1781509761000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeted Micronutrient Supplementation in Diabetic Retinopathy With MTHFR Polymorphisms: Biomarker Shifts and Clinical Uncertainty"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4369-9763","authenticated-orcid":false,"given":"Mohamed","family":"MSA.","sequence":"first","affiliation":[{"name":"MSAM Clinic Bredstedt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"e_1_2_21_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/medsci13030087"},{"key":"e_1_2_21_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12933\u2010023\u201001965\u20107"},{"key":"e_1_2_21_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26020746"},{"key":"e_1_2_21_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S358753"},{"key":"e_1_2_21_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/11772719251378813"},{"key":"e_1_2_21_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010025\u201002249\u20100"},{"key":"e_1_2_21_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1274025"},{"key":"e_1_2_21_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1169405"},{"key":"e_1_2_21_9_2","doi-asserted-by":"crossref","unstructured":"Erratum in: Front Endocrinol (Lausanne). 2023;14:1238758 https:\/\/doi.org\/10.3389\/fendo.2023.1238758.","DOI":"10.3389\/fendo.2023.1238758"},{"key":"e_1_2_21_10_1","doi-asserted-by":"publisher","DOI":"10.1515\/hmbci\u20102022\u20100093"},{"key":"e_1_2_21_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43556\u2010024\u201000214\u2010x"},{"issue":"3","key":"e_1_2_21_12_1","first-page":"133","article-title":"Shehata Marker: A Promising Tool for Assessing Graft Endothelial Dysfunction and Hypoxic Injury","volume":"15","author":"Mohamed M. 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