{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:34:21Z","timestamp":1787045661288,"version":"build-2736575974"},"reference-count":67,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"United States department of health and Human services, National Institutes of Health (NIH) USA, NIH National Cancer Institute","award":["ZIASC006321"],"award-info":[{"award-number":["ZIASC006321"]}]},{"award":["ZIASC006321"],"award-info":[{"award-number":["ZIASC006321"]}],"id":[{"id":"https:\/\/ror.org\/033jnv181","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>We investigated the effects of senescence and hypoxia on the transcriptome and secretome of the colon cancer cell, HCT-116, in an in vitro model. Senescence was confirmed using SA-\u03b2 Gal staining and the expression of p53 and p21 proteins, and hypoxia using HIF-1\u03b1 protein. Control (CN) and senescent (SN) cells were exposed to normoxia or hypoxia, control hypoxia (CH), and senescent hypoxia (SH). Senescence (SN, SH) enhanced the expression of kallikrein-related peptidases, TPp53, p21, optineurin, lipocalin, ADH-1, and stratifin by several folds. Stratifin, with tumor suppressive functions, was upregulated in senescent cells under normoxia but not in hypoxia. Hypoxia (CH and SH) upregulated the expression of many glycolysis genes, especially HK, PFK, aldolase, PDH kinase, and LDH-A. Mitochondrial RNAs (tRNA and rRNA) were increased in SH compared to CH. Significant increases in the secretion of IL-1\u03b1, endothelin, bFGF, HB-EGF, PDGF-AB, CCL-5, 7, 22, and CXCL-1 and 8 were observed in SN and SH. VEGF-A, VEGF-C, and TNF-\u03b2 secretion increased, while PLGF, TGF-\u03b1, IL-27, GM-CSF, and M-CSF decreased under hypoxic (CH and SH) conditions. Thus, senescence and hypoxia contribute to cancer cell senescence pathophysiology by regulating the cellular transcriptome and secretome and by both positive and negative feedback mechanisms.<\/jats:p>","DOI":"10.3390\/biom16081165","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:09:36Z","timestamp":1786435776000},"page":"1165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Senescence and Hypoxia Regulate Colon Cancer Cell Transcriptome and Secretome: Insights into Cancer Cell Senescence Pathophysiology"],"prefix":"10.3390","volume":"16","author":[{"given":"Chandrasekharam N.","family":"Nagineni","sequence":"first","affiliation":[{"name":"Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3187-618X","authenticated-orcid":false,"given":"Rajani","family":"Choudhuri","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murali C.","family":"Krishna","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1016\/S0140-6736(13)61649-9","article-title":"Colorectal cancer","volume":"383","author":"Brenner","year":"2014","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15065","DOI":"10.1038\/nrdp.2015.65","article-title":"Colorectal cancer","volume":"1","author":"Kuipers","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","first-page":"7","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1056\/NEJMra0804588","article-title":"Molecular origins of cancer: Molecular basis of colorectal cancer","volume":"361","author":"Markowitz","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"R921","DOI":"10.1016\/j.cub.2020.06.081","article-title":"The tumor microenvironment","volume":"30","author":"Anderson","year":"2020","journal-title":"Curr. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1158\/0008-5472.CAN-19-0928","article-title":"Molecular Imaging of the Tumor Microenvironment Reveals the Relationship between Tumor Oxygenation, Glucose Uptake, and Glycolysis in Pancreatic Ductal Adenocarcinoma","volume":"80","author":"Yamamoto","year":"2020","journal-title":"Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/ggi.13928","article-title":"Biology of extracellular vesicles secreted from senescence-associated secretory phenotype factors","volume":"20","author":"Misawa","year":"2020","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.cell.2022.12.028","article-title":"Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer","volume":"186","author":"Lin","year":"2023","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1146\/annurev-micro-102215-095513","article-title":"Gut Microbiota, Inflammation, and Colorectal Cancer","volume":"70","author":"Brennan","year":"2016","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e155101","DOI":"10.1172\/JCI155101","article-title":"Colorectal cancer: The facts in the case of the microbiota","volume":"132","author":"Clay","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/nrm3823","article-title":"Cellular senescence: From physiology to pathology","volume":"15","author":"Serrano","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.cell.2019.10.005","article-title":"Cellular Senescence: Defining a Path Forward","volume":"179","author":"Gorgoulis","year":"2019","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Martins, F., Oliveira, R., Cavadas, B., Pinto, F., Cardoso, A.P., Castro, F., Sousa, B., Pinto, M.L., Silva, A.J., and Ad\u00e3o, D. (2020). Hypoxia and Macrophages Act in Concert Towards a Beneficial Outcome in Colon Cancer. Cancers, 12.","DOI":"10.3390\/cancers12040818"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4443","DOI":"10.1002\/jcp.30906","article-title":"Modulation of tumor-associated macrophages in colitis-associated colorectal cancer","volume":"237","author":"Dong","year":"2022","journal-title":"J. Cell. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/s41577-021-00534-x","article-title":"The inflammatory pathogenesis of colorectal cancer","volume":"21","author":"Schmitt","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","article-title":"On the origin of cancer cells","volume":"123","author":"Warburg","year":"1956","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrc3038","article-title":"Otto Warburg\u2019s contributions to current concepts of cancer metabolism","volume":"11","author":"Koppenol","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2015.12.006","article-title":"The Emerging Hallmarks of Cancer Metabolism","volume":"23","author":"Pavlova","year":"2016","journal-title":"Cell Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.molcel.2010.09.022","article-title":"Hypoxia-inducible factors and the response to hypoxic stress","volume":"40","author":"Majmundar","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.ccell.2014.10.006","article-title":"Antiangiogenesis strategies revisited: From starving tumors to alleviating hypoxia","volume":"26","author":"Jain","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s12943-019-1089-9","article-title":"Role of hypoxia in cancer therapy by regulating the tumor microenvironment","volume":"18","author":"Jing","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1093\/jnci\/djq364","article-title":"Therapy-induced senescence in cancer","volume":"102","author":"Ewald","year":"2010","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tcb.2011.11.006","article-title":"Senescence: A new weapon for cancer therapy","volume":"22","author":"Acosta","year":"2012","journal-title":"Trends Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41556-018-0249-2","article-title":"The dynamic nature of senescence in cancer","volume":"21","author":"Lee","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/436642a","article-title":"Tumour biology: Senescence in premalignant tumours","volume":"436","author":"Collado","year":"2005","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nrc2772","article-title":"Senescence in tumours: Evidence from mice and humans","volume":"10","author":"Collado","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"377","DOI":"10.2174\/1389450116666151019094724","article-title":"Morphological and Functional Characteristic of Senescent Cancer Cells","volume":"17","author":"Sikora","year":"2016","journal-title":"Curr. Drug Targets"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1080\/14728222.2019.1565658","article-title":"Pro- and anti-tumorigenic functions of the senescence-associated secretory phenotype","volume":"23","author":"Lau","year":"2019","journal-title":"Expert. Opin. Ther. Targets"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cyto.2019.01.013","article-title":"The senescence-associated secretory phenotype and its regulation","volume":"117","author":"Rowell","year":"2019","journal-title":"Cytokine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/sj.bjc.6605784","article-title":"Cellular senescence predicts treatment outcome in metastasised colorectal cancer","volume":"103","author":"Haugstetter","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Schosserer, M., Grillari, J., and Breitenbach, M. (2017). The Dual Role of Cellular Senescence in Developing Tumors and Their Response to Cancer Therapy. Front. Oncol., 7.","DOI":"10.3389\/fonc.2017.00278"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1158\/2159-8290.CD-22-0523","article-title":"Cellular Senescence Is Immunogenic and Promotes Antitumor Immunity","volume":"13","author":"Marin","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1038\/s41416-018-0066-1","article-title":"Paracrine roles of cellular senescence in promoting tumourigenesis","volume":"118","author":"Apps","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Nagineni, C.N., Naz, S., Choudhuri, R., Chandramouli, G.V.R., Krishna, M.C., Brender, J.R., Cook, J.A., and Mitchell, J.B. (2021). Radiation-Induced Senescence Reprograms Secretory and Metabolic Pathways in Colon Cancer HCT-116 Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094835"},{"key":"ref_35","first-page":"1751","article-title":"Heterogeneity of malignant cells from a human colonic carcinoma","volume":"41","author":"Brattain","year":"1981","journal-title":"Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e71","DOI":"10.1038\/oncsis.2013.35","article-title":"Epigenetic and genetic features of 24 colon cancer cell lines","volume":"2","author":"Ahmed","year":"2013","journal-title":"Oncogenesis"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1038\/nprot.2009.191","article-title":"Protocols to detect senescence-associated beta-galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo","volume":"4","author":"Erusalimsky","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1158\/1541-7786.MCR-21-0202","article-title":"The Epithelial-Stromal Microenvironment in Early Colonic Neoplasia","volume":"20","author":"Ideta","year":"2022","journal-title":"Mol. Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/S0092-8674(02)00734-1","article-title":"A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy","volume":"109","author":"Schmitt","year":"2002","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/tpj.2016.13","article-title":"Glycolysis gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer","volume":"17","author":"Graziano","year":"2017","journal-title":"Pharmacogenom. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jprot.2018.02.031","article-title":"Integrated omics profiling identifies hypoxia-regulated genes in HCT116 colon cancer cells","volume":"188","author":"Chen","year":"2018","journal-title":"J. Proteom."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41419-017-0069-5","article-title":"Insight into the role of PIKK family members and NF-\u043aB in DNAdamage-induced senescence and senescence-associated secretory phenotype of colon cancer cells","volume":"9","author":"Strzeszewska","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1158\/2159-8290.CD-20-1571","article-title":"Loss of Optineurin Drives Cancer Immune Evasion via Palmitoylation-Dependent IFNGR1 Lysosomal Sorting and Degradation","volume":"11","author":"Du","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/B978-0-12-394305-7.00005-7","article-title":"Cellular and molecular biology of optineurin","volume":"294","author":"Ying","year":"2012","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Durinikova, E., Kozovska, Z., Poturnajova, M., Plava, J., Cierna, Z., Babelova, A., Bohovic, R., Schmidtova, S., Tomas, M., and Kucerova, L. (2018). ALDH1A3 upregulation and spontaneous metastasis formation is associated with acquired chemoresistance in colorectal cancer cells. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4758-y"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/bjc.2017.363","article-title":"ALDH1A3 affects colon cancer in vitro proliferation and invasion depending on CXCR4 status","volume":"118","author":"Feng","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Crescenzi, E., Leonardi, A., and Pacifico, F. (2021). NGAL as a Potential Target in Tumor Microenvironment. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212333"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.semcancer.2019.09.026","article-title":"Laminin 332 in cancer: When the extracellular matrix turns signals from cell anchorage to cell movement","volume":"62","author":"Rousselle","year":"2020","journal-title":"Semin. Cancer Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.semcancer.2006.03.008","article-title":"Epigenetic silencing of 14-3-3sigma in cancer","volume":"16","author":"Lodygin","year":"2006","journal-title":"Semin. Cancer Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3621","DOI":"10.1158\/0008-5472.CAN-20-4192","article-title":"14-3-3\u03c3 Functions as an Intestinal Tumor Suppressor","volume":"81","author":"Winter","year":"2021","journal-title":"Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1038\/nrc1474","article-title":"The emerging roles of human tissue kallikreins in cancer","volume":"4","author":"Diamandis","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1038\/sj.bjc.6605033","article-title":"The use of kallikrein-related peptidases as adjuvant prognostic markers in colorectal cancer","volume":"100","author":"Talieri","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1186\/s12935-020-01350-4","article-title":"Biomarker implication of kallikrein-related peptidases as prognostic tissue substrates of poor survival in colorectal cancer","volume":"20","author":"Peng","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Adeluola, A.A., Hossain, M.S., and Amin, A.R.M.H. (2025). Carboxypeptidase A4: A Biomarker for Cancer Aggressiveness and Drug Resistance. Cancers, 17.","DOI":"10.3390\/cancers17152566"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1111\/febs.16381","article-title":"The role of cellular senescence and SASP in tumour microenvironment","volume":"290","author":"Takasugi","year":"2023","journal-title":"FEBS J."},{"key":"ref_56","first-page":"455","article-title":"Vascular endothelial growth factor (VEGF)\u2014Key factor in normal and pathological angiogenesis","volume":"59","author":"Melincovici","year":"2018","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1152\/physrev.00030.2015","article-title":"Expression and Function of the Epidermal Growth Factor Receptor in Physiology and Disease","volume":"96","author":"Chen","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Dakowicz, D., Zajkowska, M., and Mroczko, B. (2022). Relationship between VEGF Family Members, Their Receptors and Cell Death in the Neoplastic Transformation of Colorectal Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23063375"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1080\/14712598.2020.1677603","article-title":"The role of PIGF blockade in the treatment of colorectal cancer: Overcoming the pitfalls","volume":"20","author":"Macarulla","year":"2020","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1053\/j.gastro.2016.10.015","article-title":"Transforming Growth Factor \u03b2 Superfamily Signaling in Development of Colorectal Cancer","volume":"152","author":"Jung","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3892\/ijmm.2021.4888","article-title":"Role and clinical significance of TGF-\u03b21 and TGF-\u03b2R1 in malignant tumors (Review)","volume":"47","author":"Wang","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/s41568-021-00363-z","article-title":"Interleukins in cancer: From biology to therapy","volume":"21","author":"Briukhovetska","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Bazzichetto, C., Milella, M., Zampiva, I., Simionato, F., Amoreo, C.A., Buglioni, S., Pacelli, C., Le Pera, L., Colombo, T., and Bria, E. (2022). Interleukin-8 in Colorectal Cancer: A Systematic Review and Meta-Analysis of Its Potential Role as a Prognostic Biomarker. Biomedicines, 10.","DOI":"10.3390\/biomedicines10102631"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.immuni.2012.11.003","article-title":"Interleukin-27: Balancing protective and pathological immunity","volume":"37","author":"Hunter","year":"2012","journal-title":"Immunity"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1111\/cas.12731","article-title":"Potential clinical application of interleukin-27 as an antitumor agent","volume":"106","author":"Yoshimoto","year":"2015","journal-title":"Cancer Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1093\/jb\/mvaa098","article-title":"Posttranscriptional modifications in mitochondrial tRNA and its implication in mitochondrial translation and disease","volume":"168","author":"Kazuhito","year":"2020","journal-title":"J. Biochem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41586-021-04345-x","article-title":"Local and systemic responses to SARS-CoV-2 infection in children and adults","volume":"602","author":"Yoshida","year":"2022","journal-title":"Nature"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/8\/1165\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:21:09Z","timestamp":1787044869000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/8\/1165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":67,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["biom16081165"],"URL":"https:\/\/doi.org\/10.3390\/biom16081165","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]}}}