{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T12:13:30Z","timestamp":1779884010162,"version":"3.53.1"},"reference-count":61,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["32172747&32425052"],"award-info":[{"award-number":["32172747&32425052"]}]},{"name":"Beijing Outstanding Young Scientist Program","award":["32172747&32425052"],"award-info":[{"award-number":["32172747&32425052"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>This study investigates the effect of tryptophan treatment on aged pig oocytes, focusing on its potential to reduce oxidative stress and improve oocyte quality. An oxidative stress model was induced using hydrogen peroxide (H2O2) to mimic aging effects on oocytes. Fresh ovaries from young sows were collected, and oocytes were aspirated and cultured for in vitro maturation. Oocytes in the H2O2 and the H2O2+Trp groups were exposed to 100 \u00b5M H2O2 for 30 min, with the H2O2+Trp group receiving an additional 50 \u00b5M tryptophan supplementation. RNA-sequencing was performed to study the underlying mechanism through which tryptophan mitigated the H2O2-induced oxidative stress in oocytes. The results demonstrated that tryptophan supplementation significantly reduced oxidative stress markers such as H2O2 and malonaldehyde (MDA) while restoring key antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT) confirming its antioxidant role. Furthermore, tryptophan improved cumulus cell expansion, and oocyte quality, which were compromised by oxidative stress. Transcriptomics study revealed the enrichment of several KEGG pathways, such as P13K-Akt signaling pathways as a critical regulator of cell survival and function, emphasizing the protective effects of tryptophan on oocyte integrity. Moreover, the protein\u2013protein interaction (PPI) network identified several hub genes in the tryptophan-treated group compared with H2O2, including TIMP1, CCN2, and MMP12 as key players in ECM remodeling and cellular adhesion, which are critical for restoring oocyte quality. These findings suggest that tryptophan supplementation not only mitigated oxidative stress but also modulated gene expression related to cellular functions and stress response. These results propose that tryptophan could be a valuable therapeutic strategy for improving reproductive outcomes in aging sows and other mammals facing age-related oocyte dysfunction.<\/jats:p>","DOI":"10.3390\/biom15070949","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:55:43Z","timestamp":1751442943000},"page":"949","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Transcriptomics Approach to Unveil the Antioxidant Effects of Tryptophan on Oocyte Quality Under Oxidative Stress in Pigs"],"prefix":"10.3390","volume":"15","author":[{"given":"Zhekun","family":"Zhu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"},{"name":"Beijing Key Laboratory of Bio feed Additives, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlong","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"},{"name":"Beijing Key Laboratory of Bio feed Additives, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyin","family":"Fan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"},{"name":"Beijing Key Laboratory of Bio feed Additives, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4327-7723","authenticated-orcid":false,"given":"Shuang","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"},{"name":"Beijing Key Laboratory of Bio feed Additives, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"},{"name":"Beijing Key Laboratory of Bio feed Additives, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutian","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"},{"name":"Beijing Key Laboratory of Bio feed Additives, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"},{"name":"Beijing Key Laboratory of Bio feed Additives, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjuan","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"},{"name":"Beijing Key Laboratory of Bio feed Additives, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1071\/RD14441","article-title":"Maternal Control of Early Embryogenesis in Mammals","volume":"27","author":"Zhang","year":"2015","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1038\/s41556-024-01442-7","article-title":"The Maintenance of Oocytes in the Mammalian Ovary Involves Extreme Protein Longevity","volume":"26","author":"Harasimov","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7966","DOI":"10.1002\/jcp.30468","article-title":"Oxidative Stress in Oocyte Aging and Female Reproduction","volume":"236","author":"Wang","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Sasaki, H., Hamatani, T., Kamijo, S., Iwai, M., Kobanawa, M., Ogawa, S., Miyado, K., and Tanaka, M. (2019). Impact of Oxidative Stress on Age-Associated Decline in Oocyte Developmental Competence. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00811"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/humupd\/dmn025","article-title":"ART Failure: Oocyte Contributions to Unsuccessful Fertilization","volume":"14","author":"Swain","year":"2008","journal-title":"Hum. Reprod. Update"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"hoac003","DOI":"10.1093\/hropen\/hoac003","article-title":"Oocyte Activation Deficiency and Assisted Oocyte Activation: Mechanisms, Obstacles and Prospects for Clinical Application","volume":"2022","author":"Kashir","year":"2022","journal-title":"Hum. Reprod. Open"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1038\/s41586-022-04979-5","article-title":"Oocytes Maintain ROS-Free Mitochondrial Metabolism by Suppressing Complex I","volume":"607","author":"Duran","year":"2022","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ufer, C., and Wang, C.C. (2011). The Roles of Glutathione Peroxidases during Embryo Development. Front. Mol. Neurosci., 4.","DOI":"10.3389\/fnmol.2011.00012"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4015874","DOI":"10.1155\/2017\/4015874","article-title":"Molecular Mechanisms Responsible for Increased Vulnerability of the Ageing Oocyte to Oxidative Damage","volume":"2017","author":"Mihalas","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"107186","DOI":"10.1016\/j.anireprosci.2022.107186","article-title":"V Mechanisms of Action of Non-Enzymatic Antioxidants to Control Oxidative Stress during in Vitro Follicle Growth, Oocyte Maturation, and Embryo Development","volume":"249","author":"Silva","year":"2023","journal-title":"Anim. Reprod. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s12276-024-01178-2","article-title":"Distinct Characteristics of the DNA Damage Response in Mammalian Oocytes","volume":"56","author":"Leem","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.tem.2024.03.002","article-title":"Mitochondrial Morphology, Distribution and Activity during Oocyte Development","volume":"35","author":"Bahety","year":"2024","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1093\/biolre\/ioac024","article-title":"Oocyte Mitochondria-Key Regulators of Oocyte Function and Potential Therapeutic Targets for Improving Fertility","volume":"106","author":"Adhikari","year":"2022","journal-title":"Biol. Reprod."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Prasad, S., Tiwari, M., Pandey, A.N., Shrivastav, T.G., and Chaube, S.K. (2016). Impact of Stress on Oocyte Quality and Reproductive Outcome. J. Biomed. Sci., 23.","DOI":"10.1186\/s12929-016-0253-4"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101378","DOI":"10.1016\/j.arr.2021.101378","article-title":"Mitochondria: Their Relevance during Oocyte Ageing","volume":"70","author":"Haigis","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101845","DOI":"10.1016\/j.mito.2024.101845","article-title":"Research Progress on Mitochondrial Damage and Repairing in Oocytes: A Review","volume":"75","author":"Yang","year":"2024","journal-title":"Mitochondrion"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"F109","DOI":"10.1530\/REP-22-0206","article-title":"OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: Oxidative Stress and In Vitro Ageing of the Post-Ovulatory Oocyte: An Update on Recent Advances in the Field","volume":"164","author":"Martin","year":"2022","journal-title":"Reproduction"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Long, S., Zheng, Y., Deng, X., Guo, J., Xu, Z., Scharffetter-Kochanek, K., Dou, Y., and Jiang, M. (2024). Maintaining Mitochondrial DNA Copy Number Mitigates ROS-Induced Oocyte Decline and Female Reproductive Aging. Commun. Biol., 7.","DOI":"10.1038\/s42003-024-06888-x"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/S0015-0282(16)53164-1","article-title":"Delayed Fertilization during In Vitro Fertilization and Embryo Transfer Cycles: Analysis of Causes and Impact on Overall Results","volume":"52","author":"Oehninger","year":"1989","journal-title":"Fertil. Steril."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"He, M., Zhang, T., Yang, Y., and Wang, C. (2021). Mechanisms of Oocyte Maturation and Related Epigenetic Regulation. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.654028"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s10815-022-02418-y","article-title":"In Vivo and In Vitro Postovulatory Aging: When Time Works against Oocyte Quality?","volume":"39","author":"Antonouli","year":"2022","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Alexandru, I., Nistor, D., Motofelea, A.C., Cadar, B.-A., Crintea, A., Tatu, C., Pop, G.N., and Csep, A.N. (2024). Vitamins, Coenzyme Q10, and Antioxidant Strategies to Improve Oocyte Quality in Women with Gynecological Cancers: A Comprehensive Review. Antioxidants, 13.","DOI":"10.3390\/antiox13121567"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Varela, C., and Labarta, E. (2020). Clinical Application of Antioxidants to Improve Human Oocyte Mitochondrial Function: A Review. Antioxidants, 9.","DOI":"10.3390\/antiox9121197"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Li, Y., Dong, Z., Liu, S., Gao, F., Zhang, J., Peng, Z., Wang, L., and Pan, X. (2022). Astaxanthin Improves the Development of the Follicles and Oocytes through Alleviating Oxidative Stress Induced by BPA in Cultured Follicles. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-11566-1"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Budani, M.C., and Tiboni, G.M. (2020). Effects of Supplementation with Natural Antioxidants on Oocytes and Preimplantation Embryos. Antioxidants, 9.","DOI":"10.3390\/antiox9070612"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Yang, L., Chen, Y., Liu, Y., Xing, Y., Miao, C., Zhao, Y., Chang, X., and Zhang, Q. (2020). The Role of Oxidative Stress and Natural Antioxidants in Ovarian Aging. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.617843"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2023.12.042","article-title":"Piperine Improves the Quality of Porcine Oocytes by Reducing Oxidative Stress","volume":"213","author":"Lim","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Jiao, Y., Wang, Y., Jiang, T., Wen, K., Cong, P., Chen, Y., and He, Z. (2022). Quercetin Protects Porcine Oocytes from in Vitro Aging by Reducing Oxidative Stress and Maintaining the Mitochondrial Functions. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.915898"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Jia, B.-Y., Xiang, D.-C., Shao, Q.-Y., Zhang, B., Liu, S.-N., Hong, Q.-H., Quan, G.-B., and Wu, G.-Q. (2020). Inhibitory Effects of Astaxanthin on Postovulatory Porcine Oocyte Aging In Vitro. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-77359-6"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4137\/IJTR.S1129","article-title":"Assessment of the Potential Role of Tryptophan as the Precursor of Serotonin and Melatonin for the Aged Sleep-Wake Cycle and Immune Function: Streptopelia Risoria as a Model","volume":"2","author":"Paredes","year":"2009","journal-title":"Int. J. Tryptophan Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Barik, S. (2020). The Uniqueness of Tryptophan in Biology: Properties, Metabolism, Interactions and Localization in Proteins. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228776"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/bs.acc.2019.08.005","article-title":"Tryptophan in Health and Disease","volume":"95","author":"Comai","year":"2020","journal-title":"Adv. Clin. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1178646918802282","DOI":"10.1177\/1178646918802282","article-title":"Analysis, Nutrition, and Health Benefits of Tryptophan","volume":"11","author":"Friedman","year":"2018","journal-title":"Int. J. Tryptophan Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100086","DOI":"10.1016\/j.nexres.2024.100086","article-title":"Natural Antioxidants: A Comprehensive Elucidation of Their Sources, Mechanisms, and Applications in Health","volume":"1","author":"Chibuye","year":"2024","journal-title":"Next Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"27986","DOI":"10.1039\/C4RA13315C","article-title":"Free Radicals, Natural Antioxidants, and Their Reaction Mechanisms","volume":"5","author":"Nimse","year":"2015","journal-title":"RSC Adv."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1054797","DOI":"10.1155\/2018\/1054797","article-title":"The Tryptophan Pathway Targeting Antioxidant Capacity in the Placenta","volume":"2018","author":"Xu","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wang, N., Yang, H., Chen, Y., Wang, H., Wang, C., Fan, J., Chen, Y., Li, Y., and Zhu, M. (2025). Formononetin Promotes Porcine Oocytes Maturation and Improves Embryonic Development by Reducing Oxidative Stress. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1520429"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104787","DOI":"10.1016\/j.yexmp.2022.104787","article-title":"The PI3K\/AKT Signaling Pathway in Cancer: Molecular Mechanisms and Possible Therapeutic Interventions","volume":"127","author":"Khezri","year":"2022","journal-title":"Exp. Mol. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Shcherbik, N., and Pestov, D.G. (2019). The Impact of Oxidative Stress on Ribosomes: From Injury to Regulation. Cells, 8.","DOI":"10.3390\/cells8111379"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1016\/j.bbamcr.2017.05.010","article-title":"Matrix Metalloproteinases as Regulators of Inflammatory Processes","volume":"1864","author":"Fingleton","year":"2017","journal-title":"Biochim. Biophys. Acta-Mol. Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1016\/S2095-3119(18)61942-2","article-title":"Beneficial Role of Melatonin in Protecting Mammalian Gametes and Embryos from Oxidative Damage","volume":"17","author":"Pang","year":"2018","journal-title":"J. Integr. Agric."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9463","DOI":"10.1038\/s41467-024-53559-w","article-title":"Increased DNA Damage in Full-Grown Oocytes Is Correlated with Diminished Autophagy Activation","volume":"15","author":"Sun","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_43","unstructured":"Turksen, K. (2022). Cellular Stress Responses in Oocytes: Molecular Changes and Clinical Implications. Cell Biology and Translational Medicine, Volume 16: Stem Cells in Tissue Regeneration, Therapy and Drug Discovery, Springer International Publishing."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1089\/ars.2020.8209","article-title":"Oxidative Stress in Oocytes and Embryo Development: Implications for In Vitro Systems","volume":"34","author":"Lin","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8952520","DOI":"10.1155\/2016\/8952520","article-title":"Tryptophan Biochemistry: Structural, Nutritional, Metabolic, and Medical Aspects in Humans","volume":"2016","author":"Palego","year":"2016","journal-title":"J. Amino Acids"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Khemaissa, S., Sagan, S., and Walrant, A. (2021). Tryptophan, an Amino-Acid Endowed with Unique Properties and Its Many Roles in Membrane Proteins. Crystals, 11.","DOI":"10.3390\/cryst11091032"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Cosme, P., Rodr\u00edguez, A.B., Garrido, M., and Espino, J. (2022). Coping with Oxidative Stress in Reproductive Pathophysiology and Assisted Reproduction: Melatonin as an Emerging Therapeutical Tool. Antioxidants, 12.","DOI":"10.3390\/antiox12010086"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Polyakova, V., Medvedev, D., Linkova, N., Mushkin, M., Muraviev, A., Krasichkov, A., Dyatlova, A., Ivanova, Y., Gullo, G., and Gorelova, A.A. (2024). Melatonin Receptors and Serotonin: Age-Related Changes in the Ovaries. J. Pers. Med., 14.","DOI":"10.3390\/jpm14091009"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1016\/j.bpj.2017.03.037","article-title":"Antioxidant and Membrane Binding Properties of Serotonin Protect Lipids from Oxidation","volume":"112","author":"Azouzi","year":"2017","journal-title":"Biophys. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.theriogenology.2014.07.011","article-title":"Essential Actions of Melatonin in Protecting the Ovary from Oxidative Damage","volume":"82","author":"Cruz","year":"2014","journal-title":"Theriogenology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/rda.13188","article-title":"Research Progress on the Role of Melatonin and Its Receptors in Animal Reproduction: A Comprehensive Review","volume":"53","author":"Talpur","year":"2018","journal-title":"Reprod. Domest. Anim."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"eadm7969","DOI":"10.1126\/science.adm7969","article-title":"Chemically Induced Proximity Reveals a Piezo-Dependent Meiotic Checkpoint at the Oocyte Nuclear Envelope","volume":"386","author":"Liu","year":"2024","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/s41580-022-00472-z","article-title":"Interplay between Mechanics and Signalling in Regulating Cell Fate","volume":"23","author":"Paluch","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.cellsig.2011.10.005","article-title":"Cell Surface Adhesion Molecules and Adhesion-Initiated Signaling: Understanding of Anoikis Resistance Mechanisms and Therapeutic Opportunities","volume":"24","author":"Zhong","year":"2012","journal-title":"Cell. Signal."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s12943-023-01827-6","article-title":"PI3K\/AKT\/MTOR Signaling Transduction Pathway and Targeted Therapies in Cancer","volume":"22","author":"Glaviano","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13058-020-01298-3","article-title":"FAK Activates AKT-MTOR Signaling to Promote the Growth and Progression of MMTV-Wnt1-Driven Basal-like Mammary Tumors","volume":"22","author":"Paul","year":"2020","journal-title":"Breast Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41556-023-01088-x","article-title":"Niche Tension Controls Exosome Production","volume":"25","author":"Dawson","year":"2023","journal-title":"Nat. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Abbas, Z., Tong, Y., Zhang, J., Sammad, A., Wang, J., Ahmad, B., Wei, X., Si, D., and Zhang, R. (2025). Transcriptomics and Microbiome Insights Reveal the Protective Mechanism of Mulberry-Derived Postbiotics against Inflammation in LPS-Induced Mice. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1536694"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Deng, J., Wei, R.-Q., Zhang, W.-M., Shi, C.-Y., Yang, R., Jin, M., and Piao, C. (2024). Crocin\u2019s Role in Modulating MMP2\/TIMP1 and Mitigating Hypoxia-Induced Pulmonary Hypertension in Mice. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-62900-8"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.matbio.2015.03.005","article-title":"The Role of TIMPs in Regulation of Extracellular Matrix Proteolysis","volume":"44","author":"Arpino","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s00018-013-1457-3","article-title":"Cytokine Functions of TIMP-1","volume":"71","author":"Ries","year":"2014","journal-title":"Cell. Mol. Life Sci."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/7\/949\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:02:02Z","timestamp":1760032922000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/7\/949"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,30]]},"references-count":61,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["biom15070949"],"URL":"https:\/\/doi.org\/10.3390\/biom15070949","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,30]]}}}