{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:04:33Z","timestamp":1790597073110,"version":"4.1.0"},"reference-count":116,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Pathological biomineralization is increasingly recognized as a regulated biological process involving interactions among mineral metabolism, inflammation, cellular stress, extracellular vesicles (EVs), extracellular matrix (ECM) components, and mineral precursors. These processes are particularly well characterized in vascular calcification, where immune, metabolic, vesicular, and matrix-associated pathways contribute to ectopic mineral deposition. Tumor-associated mineralization is also documented in several malignancies, but its cellular origins, mineral composition, and biological significance remain substantially less defined. The Immuno\u2013Biomineral Interface (IBI) is proposed here as a hypothesis-generating conceptual framework for integrating these interacting processes and examining potential mechanistic connections between established vascular calcification pathways and tumor-associated biomineralization. Nutritional status can modulateseveral biological processes implicated in pathological calcification, including mineral homeostasis, inflammatory signaling, oxidative stress, ECM remodeling, and EV biology. Magnesium, vitamin K2, omega-3 fatty acids, and selected polyphenols have been investigated in experimental and clinical contexts, although the strength and consistency of evidence vary according to nutrient, dose, biological system, and outcome. The strongest evidence for nutritional modulation of pathological calcification derives from vascular and renal contexts. These findings provide a mechanistic basis for considering nutrition as a potentially modifiable influence on IBI-associated processes, rather than as a single upstream determinant of pathological biomineralization. Most mechanistic evidence reviewed here derives from vascular calcification. Tumor microenvironments nevertheless exhibit processes also implicated in pathological calcification, including chronic inflammation, ECM remodeling, altered calcium and mineral handling, cellular stress, and EV-mediated communication. These observations identify potential points of mechanistic convergence but do not demonstrate that vascular and tumor-associated mineralization arise through equivalent pathways. Importantly, direct evidence that defined nutritional exposures modify the initiation, composition, maturation, or spatial distribution of tumor-associated mineral deposits remains scarce. The proposed nutrition\u2013IBI\u2013tumor biomineralization relationship should therefore be regarded as a testable, hypothesis-generating model rather than an established causal pathway. Asa narrative review, we integrate evidence from nutritional science, vascular biology, immunology, EV research, mineral metabolism, and cancer biology to critically distinguish established mechanisms from indirect evidence and hypothesis-generating extrapolations. We further highlight key knowledge gaps concerning nutrient-dependent regulation of immune responses, EV biology, matrix remodeling, and mineral formation within tumor microenvironments. Future studies combining defined nutritional interventions with spatial molecular profiling, EV characterization, high-resolution mineral characterization, and quantitative pathology will be required to determine whether mechanisms established in vascular calcification extend to tumor-associated biomineralization. The principal value of the IBI framework is therefore to organize existing evidence and define experimentally testable relationships between nutrition, pathological mineralization, and tumor biology while maintaining clear boundaries between established and unvalidated mechanisms.<\/jats:p>","DOI":"10.3390\/nu18193198","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:35:59Z","timestamp":1790595359000},"page":"3198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nutritional Modulation of the Immuno\u2013Biomineral Interface: From Vascular Calcification to a Hypothesis-Generating Framework for Tumor-Associated Biomineralization"],"prefix":"10.3390","volume":"18","author":[{"given":"Nishmitha N.","family":"Hegde","sequence":"first","affiliation":[{"name":"Department of Conservative Dentistry and Endodontics, Nitte (Deemed to Be University), AB Shetty Memorial Institute of Dental Sciences (ABSMIDS), Deralakatte, Mangalore 575018, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7971-6770","authenticated-orcid":false,"given":"Jayalaxmi","family":"Shetty","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry and Endodontics, Nitte (Deemed to Be University), AB Shetty Memorial Institute of Dental Sciences (ABSMIDS), Deralakatte, Mangalore 575018, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0203-3415","authenticated-orcid":false,"given":"Chaithra","family":"Lakshmi","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry and Endodontics, Nitte (Deemed to Be University), AB Shetty Memorial Institute of Dental Sciences (ABSMIDS), Deralakatte, Mangalore 575018, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5618-6778","authenticated-orcid":false,"given":"Mithra N.","family":"Hegde","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry and Endodontics, Nitte (Deemed to Be University), AB Shetty Memorial Institute of Dental Sciences (ABSMIDS), Deralakatte, Mangalore 575018, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/imr.13134","article-title":"Small particles with large impact: Insights into the unresolved roles of innate immunity in extracellular vesicle-mediated cardiovascular calcification","volume":"312","author":"Turner","year":"2022","journal-title":"Immunol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1525-139X.2007.00255.x","article-title":"The vascular biology of calcification","volume":"20","author":"Shroff","year":"2007","journal-title":"Semin. Dial."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1007\/s00424-025-03098-0","article-title":"Soft tissue calcifications in chronic kidney disease\u2014Beyond the vasculature","volume":"477","author":"Fajol","year":"2025","journal-title":"Pflug. Arch."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"i3","DOI":"10.1093\/ndtplus\/sfr163","article-title":"Magnesium basics","volume":"5","author":"Ketteler","year":"2012","journal-title":"Clin. Kidney J."},{"key":"ref_5","first-page":"183","article-title":"Arterial calcification in chronic kidney disease","volume":"22","author":"Shanahan","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1161\/ATVBAHA.113.302070","article-title":"Inflammatory, metabolic, and genetic mechanisms of vascular calcification","volume":"34","author":"Demer","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1161\/01.RES.0000249379.55535.21","article-title":"Vascular calcification: Pathobiological mechanisms and clinical implications","volume":"99","author":"Johnson","year":"2006","journal-title":"Circ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bonfiglio, R., Granaglia, A., Giocondo, R., Scimeca, M., and Bonanno, E. (2021). Molecular aspects and prognostic significance of microcalcifications in human pathology: A narrative review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010120"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ferreira, L.B., Gimba, E., Vinagre, J., Sobrinho-Simoes, M., and Soares, P. (2020). Molecular aspects of thyroid calcification. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207718"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sacco, S.M., and L\u2019Abb\u00e9, M.R. (2015). Calcium: Physiology. Encyclopedia of Food and Health, Elsevier.","DOI":"10.1016\/B978-0-12-384947-2.00103-3"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1053\/j.ajkd.2013.03.042","article-title":"Phosphate homeostasis in CKD: Report of a scientific symposium sponsored by the national kidney foundation","volume":"62","author":"Block","year":"2013","journal-title":"Am. J. Kidney Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bergwitz, C. (2026). Phosphate homeostasis and endocrine regulators. Pediatr. Nephrol.","DOI":"10.1007\/s00467-026-07399-z"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.bonr.2018.07.002","article-title":"Vitamin D and kidney disease","volume":"9","author":"Keung","year":"2018","journal-title":"Bone Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00109-007-0294-y","article-title":"Mineral chaperones: A role for fetuin-A and osteopontin in the inhibition and regression of pathologic calcification","volume":"86","author":"Ketteler","year":"2008","journal-title":"J. Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1161\/CIRCULATIONAHA.107.743161","article-title":"Vascular calcification: Pathobiology of a multifaceted disease","volume":"117","author":"Demer","year":"2008","journal-title":"Circulation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1161\/ATVBAHA.123.319198","article-title":"Phosphate in Cardiovascular Disease: From New Insights into Molecular Mechanisms to Clinical Implications","volume":"44","author":"Turner","year":"2024","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1038\/s41580-020-00298-7","article-title":"Cell\u2013cell interfaces as specialized compartments directing cell function","volume":"21","author":"Belardi","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.ssnmr.2019.06.001","article-title":"Structural description of surfaces and interfaces in biominerals by DNP SENS","volume":"102","author":"Ajili","year":"2019","journal-title":"Solid State Nucl. Magn. Reson."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Omar, O., Shah, F.A., Ruscs\u00e1k, K., Sayardoust, S., Palmquist, A., and Thomsen, P. (2019). Cellular and Molecular Reactions to Dental Implants. Dental Implants and Bone Grafts: Materials and Biological Issues, Woodhead Publishing.","DOI":"10.1016\/B978-0-08-102478-2.00008-8"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1089\/ten.2006.12.2789","article-title":"Strategies to promote chondrogenesis and osteogenesis from human bone marrow cells and articular chondrocytes encapsulated in polysaccharide templates","volume":"12","author":"Pound","year":"2006","journal-title":"Tissue Eng."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1021\/ar300321e","article-title":"Solid-state NMR studies of biomineralization peptides and proteins","volume":"46","author":"Roehrich","year":"2013","journal-title":"Acc. Chem. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3420","DOI":"10.1021\/acs.chemrev.9b00410","article-title":"Structure and Dynamics of Interfacial Peptides and Proteins from Vibrational Sum-Frequency Generation Spectroscopy","volume":"120","author":"Hosseinpour","year":"2020","journal-title":"Chem. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/wnan.1195","article-title":"Investigative and clinical applications of synthetic immune synapses","volume":"5","author":"Milone","year":"2013","journal-title":"Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.coi.2007.05.003","article-title":"Patterned surfaces as tools to study ligand recognition and synapse formation by T cells","volume":"19","author":"Irvine","year":"2007","journal-title":"Curr. Opin. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sasidharan, S., Davis, D.M., and Dunlop, I.E. (2024). Bioinspired Materials for Immunoengineering of T Cells and Natural Killer Cells. Adv. Funct. Mater., 34.","DOI":"10.1002\/adfm.202307433"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1093\/zoolinnean\/zlad099","article-title":"Shell formation in two species of bivalves: The role of mantle cells and haemocytes","volume":"200","author":"Alesci","year":"2024","journal-title":"Zool. J. Linn. Soc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ijcard.2019.09.068","article-title":"High-phosphate induced vascular calcification is reduced by iron citrate through inhibition of extracellular matrix osteo-chondrogenic shift in VSMCs","volume":"297","author":"Ciceri","year":"2019","journal-title":"Int. J. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Raju, S., and Saxena, R. (2025). Hyperphosphatemia in Kidney Failure: Pathophysiology, Challenges, and Critical Role of Phosphorus Management. Nutrients, 17.","DOI":"10.20944\/preprints202503.2193.v2"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s00467-004-1614-x","article-title":"\u201cMissing\u201d inhibitors of calcification: General aspects and implications in renal failure","volume":"20","author":"Ketteler","year":"2005","journal-title":"Pediatr. Nephrol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.atherosclerosis.2018.08.046","article-title":"CKD, arterial calcification, atherosclerosis and bone health: Inter-relationships and controversies","volume":"278","author":"Reiss","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.freeradbiomed.2020.04.008","article-title":"Reactive oxygen species (ROS) generation as an underlying mechanism of inorganic phosphate (Pi)-induced mineralization of osteogenic cells","volume":"153","author":"Khalid","year":"2020","journal-title":"Free Radic. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wang, Z., Gui, Z., Zhang, L., and Wang, Z. (2025). Advances in the mechanisms of vascular calcification in chronic kidney disease. J. Cell Physiol., 240.","DOI":"10.1002\/jcp.31464"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"C553","DOI":"10.1152\/ajpcell.00096.2006","article-title":"Calcium controls smooth muscle TRPC gene transcription via the CaMK\/calcineurin-dependent pathways","volume":"292","author":"Morales","year":"2007","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Koide, T., Giles, W.R., Kondo, R., Imaizumi, Y., Yamamura, H., and Suzuki, Y. (2025). Ca2+ microdomain-based excitation-transcription coupling in cardiac myocytes and vascular smooth muscle cells. Inflamm. Regen., 45.","DOI":"10.1186\/s41232-025-00384-3"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1093\/abbs\/gmaa098","article-title":"ROS signaling cascades: Dual regulations for osteoclast and osteoblast","volume":"52","author":"Tao","year":"2020","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"161","DOI":"10.2220\/biomedres.34.161","article-title":"Involvement of reactive oxygen species in osteoblastic differentiation of MC3T3-E1 cells accompanied by mitochondrial morphological dynamics","volume":"34","author":"Arakaki","year":"2013","journal-title":"Biomed. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.freeradbiomed.2022.08.002","article-title":"Reactive sulfur and selenium species in the regulation of bone homeostasis","volume":"190","author":"Gilbert","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10650","DOI":"10.1007\/s10853-024-09793-0","article-title":"Calcium-based nanomaterials for cancer therapy","volume":"59","author":"Huang","year":"2024","journal-title":"J. Mater. Sci."},{"key":"ref_39","first-page":"2254","article-title":"The role of reactive oxygen species in periodontitis and periodontal tissue regeneration","volume":"28","author":"Zhai","year":"2024","journal-title":"Chin. J. Tissue Eng. Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Cui, Z., Feng, C., Chen, J., Wang, Y., Meng, Q., Zhao, S., Zhang, Y., Feng, D., Li, Z., and Sun, S. (2022). Network Pharmacology Deciphers the Action of Bioactive Polypeptide in Attenuating Inflammatory Osteolysis via the Suppression of Oxidative Stress and Restoration of Bone Remodeling Balance. Oxid. Med. Cell Longev., 2022.","DOI":"10.1155\/2022\/4913534"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Estev\u00e3o, P., Martins, A.J.E., and Moraes-Vieira, P.M. (2026). Macronutrient availability and immune cell responses. Semin. Immunol., 82.","DOI":"10.1016\/j.smim.2026.102027"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/odi.14064","article-title":"Updates of liquid biopsy in oral cancer and multiomics analysis","volume":"29","author":"Zhang","year":"2023","journal-title":"Oral Dis."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Manr\u00edquez-N\u00fa\u00f1ez, J., Mora, O., Villarroya, F., Reynoso-Camacho, R., P\u00e9rez-Ram\u00edrez, I.F., and Ramos-G\u00f3mez, M. (2023). Macrophage Activity under Hyperglycemia: A Study of the Effect of Resveratrol and 3H-1,2-Dithiole-3-thione on Potential Polarization. Molecules, 28.","DOI":"10.3390\/molecules28165998"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liu, S., Jing, J., Zhang, Y., Sun, J., and Zhu, C. (2025). Potential of herbal formulas and bioactive metabolites in treating atherosclerosis: Targeted modulation of macrophage polarization. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1631274"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Shrivastava, A., Patel, P.C., Tiwari, M., Shanno, K., Soni, S., Sahu, P.K., Goyal, S., Dwivedi, S., Singh, K., and Al Noman, A. (2025). Recent Advances in Self-Management Strategies, Vascular Calcification Mechanisms, and Inflammatory Processes in Cardiovascular Disorders: A Comprehensive Review. Catheterization and Cardiovascular Interventions, John Wiley and Sons Inc.","DOI":"10.1002\/ccd.70180"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Khuspe, P.R., Pagar, R., Pardeshi, S.R., Meshram, P.D., Gholap, A.D., Dhole, S.J., Kole, E.B., and Naik, J.B. (2025). Phytochemicals as Promising Therapeutic Approaches for Inflammasomes-Related Metabolic Disorders. Plant-Based Drug Discovery: Unveiling Molecular Targets for Metabolic Conditions, Academic Press.","DOI":"10.1016\/B978-0-443-31698-2.00022-9"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/s41374-018-0177-6","article-title":"Impaired mitophagy triggers NLRP3 inflammasome activation during the progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis","volume":"99","author":"Zhang","year":"2019","journal-title":"Lab. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/nrneph.2015.74","article-title":"Magnesium and cardiovascular complications of chronic kidney disease","volume":"11","author":"Massy","year":"2015","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mu\u00f1oz-Casta\u00f1eda, J.R., Pend\u00f3n-Ruiz De Mier, M.V., Rodr\u00edguez, M., and Rodr\u00edguez-Ortiz, M.E. (2018). Magnesium replacement to protect cardiovascular and kidney damage? Lack of prospective clinical trials. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030664"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1097\/CRD.0000000000000003","article-title":"Role of magnesium in cardiovascular diseases","volume":"22","author":"Kolte","year":"2014","journal-title":"Cardiol. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Severino, P., Netti, L., Mariani, M.V., Maraone, A., D\u2019aMato, A., Scarpati, R., Infusino, F., Pucci, M., Lavalle, C., and Maestrini, V. (2019). Prevention of cardiovascular disease: Screening for magnesium deficiency. Cardiol. Res. Pract., 2019.","DOI":"10.1155\/2019\/4874921"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Ter Braake, A.D., Tinnemans, P.T., Shanahan, C.M., Hoenderop, J.G.J., and De Baaij, J.H.F. (2018). Magnesium prevents vascular calcification in vitro by inhibition of hydroxyapatite crystal formation. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-20241-3"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1093\/ndt\/gfs520","article-title":"Magnesium prevents phosphate-induced calcification in human aortic vascular smooth muscle cells","volume":"28","author":"Louvet","year":"2013","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Cunha, A.R., Umbelino, B., Correia, M.L., and Neves, M.F. (2012). Magnesium and vascular changes in hypertension. Int. J. Hypertens., 2012.","DOI":"10.1155\/2012\/754250"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1159\/000339380","article-title":"Magnesium: Novel applications in cardiovascular disease\u2014A review of the literature","volume":"61","author":"Uitto","year":"2012","journal-title":"Ann. Nutr. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Sakaguchi, Y., Hamano, T., and Isaka, Y. (2017). Effects of magnesium on the phosphate toxicity in chronic kidney disease: Time for intervention studies. Nutrients, 9.","DOI":"10.3390\/nu9020112"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Vermeulen, E.A., Eelderink, C., Hoekstra, T., van Ballegooijen, A.J., Raijmakers, P., Beulens, J.W., de Borst, M.H., and Vervloet, M.G. (2022). Reversal Of Arterial Disease by modulating Magnesium and Phosphate (ROADMAP-study): Rationale and design of a randomized controlled trial assessing the effects of magnesium citrate supplementation and phosphate-binding therapy on arterial stiffness in moderate chronic kidney disease. Trials, 23.","DOI":"10.1186\/s13063-022-06562-9"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1160\/TH08-02-0087","article-title":"Matrix Gla-protein: The calcification inhibitor in need of vitamin K","volume":"100","author":"Schurgers","year":"2008","journal-title":"Thromb. Haemost."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Jadhav, N., Ajgaonkar, S., Saha, P., Gurav, P., Pandey, A., Basudkar, V., Gada, Y., Panda, S., Jadhav, S., and Mehta, D. (2022). Molecular Pathways and Roles for Vitamin K2-7 as a Health-Beneficial Nutraceutical: Challenges and Opportunities. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.896920"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1161\/ATVBAHA.119.312787","article-title":"Role of vascular smooth muscle cell phenotypic switching and calcification in aortic aneurysm formation involvement of Vitamin K-dependent processes","volume":"39","author":"Petsophonsakul","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1080\/17843286.2016.1180770","article-title":"The role of vitamin K in vascular calcification of patients with chronic kidney disease","volume":"71","author":"Wuyts","year":"2016","journal-title":"Acta Clin. Belg. Int. J. Clin. Lab. Med."},{"key":"ref_62","first-page":"3","article-title":"Vitamin K-dependent proteins involved in bone and cardiovascular health (Review)","volume":"18","author":"Wen","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.2146\/ajhp040357","article-title":"Vitamin K in the treatment and prevention of osteoporosis and arterial calcification","volume":"62","author":"Adams","year":"2005","journal-title":"Am. J. Health-Syst. Pharm."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.1182\/blood-2006-08-040709","article-title":"Vitamin K-containing dietary supplements: Comparison of synthetic vitamin K 1 and natto-derived menaquinone-7","volume":"109","author":"Schurgers","year":"2007","journal-title":"Blood"},{"key":"ref_65","first-page":"2433","article-title":"Something more to say about calcium homeostasis: The role of vitamin K2 in vascular calcification and osteoporosis","volume":"17","author":"Flore","year":"2013","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.bbamcr.2018.02.010","article-title":"Nrf2-Keap1 signaling in oxidative and reductive stress","volume":"1865","author":"Bellezza","year":"2018","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Cell Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Liu, T., Zhang, L., Joo, D., and Sun, S.C. (2017). NF-\u03baB signaling in inflammation. Signal Transduct. Target. Ther., 2.","DOI":"10.1038\/sigtrans.2017.23"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1002\/ptr.6674","article-title":"Curcumin inhibits calcification of human aortic valve interstitial cells by interfering NF-\u03baB, AKT, and ERK pathways","volume":"34","author":"Zhou","year":"2020","journal-title":"Phyther. Res."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Chen, Y., Xie, Y., Liu, M., Hu, J., Tang, C., Huang, J., Qin, T., Chen, X., Chen, W., and Shen, W. (2019). Controlled-release curcumin attenuates progression of tendon ectopic calcification by regulating the differentiation of tendon stem\/progenitor cells. Mater. Sci. Eng. C, 103.","DOI":"10.1016\/j.msec.2019.04.090"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Huang, X., Wang, Y., Qiu, Y., Shi, Q., Sun, D., Yang, J., Dai, C., and He, W. (2022). Resveratrol ameliorates high-phosphate-induced VSMCs to osteoblast-like cells transdifferentiation and arterial medial calcification in CKD through regulating Wnt\/\u03b2-catenin signaling. Eur. J. Pharmacol., 925.","DOI":"10.1016\/j.ejphar.2022.174953"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.bbrc.2020.07.136","article-title":"Metformin, resveratrol, and exendin-4 inhibit high phosphate-induced vascular calcification via AMPK-RANKL signaling","volume":"530","author":"Lee","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Hou, M., Wang, H., Cheng, J., Duan, X., Ren, M., and Lu, Y. (2025). Resveratrol ameliorates osteogenic differentiation, calcification, and apoptosis of VSMCs through regulating JNK\/Bax signaling. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1631039"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Chen, S., Liang, H., Ji, Y., Kou, H., Zhang, C., Shang, G., Shang, C., Song, Z., Yang, L., and Liu, L. (2021). Curcumin Modulates the Crosstalk Between Macrophages and Bone Mesenchymal Stem Cells to Ameliorate Osteogenesis. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.634650"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Li, Y., Yao, J., Han, C., Yang, J., Chaudhry, M.T., Wang, S., Liu, H., and Yin, Y. (2016). Quercetin, inflammation and immunity. Nutrients, 8.","DOI":"10.3390\/nu8030167"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Li, S., Li, Q., Zhou, Q., Li, S., Wang, S., Yao, Q., Ouyang, C., Liu, C., and Li, M. (2024). Attenuating Atherosclerosis through Inhibition of the NF-\u03baB\/NLRP3\/IL-1\u03b2 Pathway-Mediated Pyroptosis in Vascular Smooth Muscle Cells (VSMCs). Cardiovasc. Ther., 2024.","DOI":"10.1155\/2024\/1506083"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/j.bcp.2011.07.093","article-title":"Green tea catechin, epigallocatechin-3-gallate (EGCG): Mechanisms, perspectives and clinical applications","volume":"82","author":"Singh","year":"2011","journal-title":"Biochem. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nri3073","article-title":"Protective and pathogenic functions of macrophage subsets","volume":"11","author":"Murray","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Orecchioni, M., Ghosheh, Y., Pramod, A.B., and Ley, K. (2019). Macrophage polarization: Different gene signatures in M1(Lps+) vs. Classically and M2(LPS-) vs. Alternatively activated macrophages. Front. Immunol., 10, Correction in Front. Immunol. 2020, 11, 234. https:\/\/doi.org\/10.3389\/fimmu.2020.00234.","DOI":"10.3389\/fimmu.2019.01084"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/j.1365-2125.2012.04374.x","article-title":"Omega-3 polyunsaturated fatty acids and inflammatory processes: Nutrition or pharmacology?","volume":"75","author":"Calder","year":"2013","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s00281-019-00767-y","article-title":"The resolution of inflammation through omega-3 fatty acids in atherosclerosis, intimal hyperplasia, and vascular calcification","volume":"41","author":"Carracedo","year":"2019","journal-title":"Semin. Immunopathol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Bodur, M., Yilmaz, B., A\u011fag\u00fcnd\u00fcz, D., and Ozogul, Y. (2025). Immunomodulatory Effects of Omega-3 Fatty Acids: Mechanistic Insights and Health Implications. Mol. Nutr. Food Res., 69.","DOI":"10.1002\/mnfr.202400752"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Xue, B., Yang, Z., Wang, X., and Shi, H. (2012). Omega-3 Polyunsaturated Fatty Acids Antagonize Macrophage Inflammation via Activation of AMPK\/SIRT1 Pathway. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045990"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Gladine, C., Zmojdzian, M., Joumard-Cubizolles, L., Verny, M.A., Comte, B., and Mazur, A. (2014). The omega-3 fatty acid docosahexaenoic acid favorably modulates the inflammatory pathways and macrophage polarization within aorta of LDLR\u2212\/\u2212 mice. Genes Nutr., 9.","DOI":"10.1007\/s12263-014-0424-4"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Videla, L.A., Valenzuela, R., Del Campo, A., and Z\u00fa\u00f1iga-Hern\u00e1ndez, J. (2023). Omega-3 Lipid Mediators: Modulation of the M1\/M2 Macrophage Phenotype and Its Protective Role in Chronic Liver Diseases. Int. J. Mol. Sci., 24.","DOI":"10.20944\/preprints202310.0145.v1"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Zhao, X., Yu, J., Zhang, T., Zhang, Y., Zhang, L., Wang, Y., Yi, C., Pan, H., Wang, H., and Ge, M. (2026). \u03a9-3 PUFAs Attenuate Postoperative Ileus by Modulating Macrophage Polarization via the JAK2\/STAT3 Signaling Pathway. J. Inflamm. Res., 19.","DOI":"10.2147\/JIR.S562643"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature13479","article-title":"Pro-resolving lipid mediators are leads for resolution physiology","volume":"510","author":"Serhan","year":"2014","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Serhan, C.N., Chiang, N., and Dalli, J. (2015). The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution. Seminars in Immunology, Academic Press.","DOI":"10.1016\/j.smim.2015.03.004"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nri.2015.4","article-title":"Specialized pro-resolving mediators: Endogenous regulators of infection and inflammation","volume":"16","author":"Basil","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"5408","DOI":"10.4049\/jimmunol.1100225","article-title":"Resolvin D1 and its precursor docosahexaenoic acid promote resolution of adipose tissue inflammation by eliciting macrophage polarization toward an M2-like phenotype","volume":"187","author":"Titos","year":"2011","journal-title":"J. Immunol."},{"key":"ref_90","first-page":"377","article-title":"Alpha-Linolenic Acid Attenuates Inflammatory Response in LPS-stimulated Macrophages by Regulating TLR4\/MyD88\/NF-\u03baB Signaling Pathway","volume":"46","author":"Cai","year":"2025","journal-title":"Sci. Technol. Food Ind."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.tcm.2012.07.009","article-title":"Calcium Regulation of Vascular Smooth Muscle Cell-Derived Matrix Vesicles","volume":"22","author":"Kapustin","year":"2012","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Y\u00e1\u00f1ez-M\u00f3, M., Siljander, P.R., Andreu, Z., Zavec, A.B., Borr\u00e0s, F.E., Buzas, E.I., Buzas, K., Casal, E., Cappello, F., and Carvalho, J. (2015). Biological properties of extracellular vesicles and their physiological functions. J. Extracell. Vesicles, 4.","DOI":"10.3402\/jev.v4.27066"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.xfss.2026.04.003","article-title":"Extracellular vesicles released by uterine fibroid cells: Modulation by omega-3 fatty acids and impact on recipient myometrial cells","volume":"7","author":"Greco","year":"2026","journal-title":"F&S Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1161\/HYPERTENSIONAHA.125.25101","article-title":"Effects of Dietary Sodium Modulation on Circulating Extracellular Vesicles","volume":"82","author":"Burrello","year":"2025","journal-title":"Hypertension"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1194\/jlr.E086173","article-title":"Extracellular vesicles: Lipids as key components of their biogenesis and functions","volume":"59","author":"Record","year":"2018","journal-title":"J. Lipid Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/j.bbalip.2013.04.011","article-title":"Molecular lipidomics of exosomes released by PC-3 prostate cancer cells","volume":"1831","author":"Llorente","year":"2013","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Th\u00e9ry, C., Witwer, K.W., Aikawa, E., Alcaraz, M.J., Anderson, J.D., Andriantsitohaina, R., Antoniou, A., Arab, T., Archer, F., and Atkin-Smith, G.K. (2018). Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles, 7.","DOI":"10.1080\/20013078.2018.1461450"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Kalluri, R., and LeBleu, V.S. (2020). The biology, function, and biomedical applications of exosomes. Science, 367.","DOI":"10.1126\/science.aau6977"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1002\/mnfr.201300729","article-title":"Interspecies communication between plant and mouse gut host cells through edible plant derived exosome-like nanoparticles","volume":"58","author":"Mu","year":"2014","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.chom.2018.10.001","article-title":"Plant-Derived Exosomal MicroRNAs Shape the Gut Microbiota","volume":"24","author":"Teng","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_102","first-page":"2782","article-title":"Inflammation and calcification","volume":"116","author":"Aikawa","year":"2007","journal-title":"Circulation"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1161\/CIRCRESAHA.116.305012","article-title":"Vascular smooth muscle cell calcification is mediated by extracellular vesicles","volume":"116","author":"Kapustin","year":"2015","journal-title":"Circ. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1016\/j.bbagen.2009.09.006","article-title":"Role of matrix vesicles in biomineralization","volume":"1790","author":"Golub","year":"2009","journal-title":"Biochim. Biophys. Acta-Gen. Subj."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1007\/s11926-003-0071-z","article-title":"Matrix vesicles and calcification","volume":"5","author":"Anderson","year":"2003","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1007\/s10753-024-02146-8","article-title":"Bacterial Extracellular Vesicles as Potential Promoting Factors for Oral Lichen Planus Pathogenesis","volume":"48","author":"Kim","year":"2025","journal-title":"Inflammation"},{"key":"ref_107","first-page":"305","article-title":"Evidence that breast cancer associated microcalcifications are mineralized malignant cells","volume":"12","author":"Castronovo","year":"1998","journal-title":"Int. J. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s10911-005-5400-6","article-title":"Microcalcifications associated with breast cancer: An epiphenomenon or biologically significant feature of selected tumors?","volume":"10","author":"Morgan","year":"2005","journal-title":"J. Mammary Gland. Biol. Neoplasia"},{"key":"ref_109","first-page":"5375","article-title":"Identifying microcalcifications in benign and malignant breast lesions by probing differences in their chemical composition using Raman spectroscopy","volume":"62","author":"Haka","year":"2002","journal-title":"Cancer Res."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Wang, S., Li, H., Ren, Y., Yu, F., Song, D., Zhu, L., Yu, S., Jiang, S., and Zeng, H. (2021). Studying the pathological and biochemical features in breast cancer progression by confocal Raman microspectral imaging of excised tissue samples. J. Photochem. Photobiol. B Biol., 222.","DOI":"10.1016\/j.jphotobiol.2021.112280"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.bone.2013.01.013","article-title":"Microcalcifications in breast cancer: Lessons from physiological mineralization","volume":"53","author":"Cox","year":"2013","journal-title":"Bone"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/bjc.2011.583","article-title":"Microcalcifications in breast cancer: Novel insights into the molecular mechanism and functional consequence of mammary mineralisation","volume":"106","author":"Cox","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"O\u2019Grady, S., and Morgan, M.P. (2019). Deposition of calcium in an in vitro model of human breast tumour calcification reveals functional role for ALP activity, altered expression of osteogenic genes and dysregulation of the TRPM7 ion channel. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-36496-9"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Scimeca, M., Giannini, E., Antonacci, C., Pistolese, C.A., Spagnoli, L.G., and Bonanno, E. (2014). Microcalcifications in breast cancer: An active phenomenon mediated by epithelial cells with mesenchymal characteristics. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-286"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Cory, H., Passarelli, S., Szeto, J., Tamez, M., and Mattei, J. (2018). The Role of Polyphenols in Human Health and Food Systems: A Mini-Review. Front. Nutr., 5.","DOI":"10.3389\/fnut.2018.00087"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/19\/3198\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:52:39Z","timestamp":1790596359000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/19\/3198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":116,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["nu18193198"],"URL":"https:\/\/doi.org\/10.3390\/nu18193198","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,28]]}}}