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Molecular Targets and Repositioned Drugs For the Treatment of Post Traumatic Stress Disorder (PTSD)

Yıl 2023, Cilt: 23 Sayı: 2, 532 - 546, 03.05.2023

Elıf Kubat Oktem

https://doi.org/10.35414/akufemubid.1173072

Öz

Post-traumatic stress disorder (PTSD) is a mental illness caused by trauma following an accident
involving physical injury or by mental shock such as anxiety. Although it is common in the population,
the prognosis and optimal therapies for PTSD are limited. Because the molecular targets for early
intervention remain unclear, a better understanding of the molecular basis of the pathogenesis of PTSD
is essential to address the challenges of disease prognosis and to diagnose and treat these molecular
targets. In this study, performed by processing and analyzing microarray data from two different tissues
of mice exposed to stress, genes with differential expression for the two tissue types were identified,
the signaling pathways in which these genes are enriched were found, the protein-protein interaction
networks of these genes and the hub proteins in these networks were determined. As a result of
comparing the drug repositioning studies performed separately for the two different tissue types to
reverse the effects of differentially expressed genes, vorinostat, homoharringtonine, and QL-XII -47
were proposed as novel drugs for the treatment of PTSD. Vorinostat, one of these drugs, was also found
to target HDAC1, HDAC2, HDAC3, HDAC6, HDAC7, and HDAC8 genes in the cell.

Anahtar Kelimeler

PTSD systems biology drug repositioning Bioinformatics

Kaynakça

  • Adshead, G. (2000). Psychological therapies for post-traumatic stress disorder. The British Journal of Psychiatry, 177, 144–148.
  • Albrechet-Souza, L., Carvalho, M. C., and Brandão, M. L. (2013). D1-like receptors in the nucleus accumbens shell regulate the expression of contextual fear conditioning and activity of the anterior cingulate cortex in rats. International Journal of Neuropsychopharmacology, 16(5), 1045–1057. https://doi.org/10.1017/S146114571200082X
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  • Antoniadis, E. A., and McDonald, R. J. (2006). Fornix, medial prefrontal cortex, nucleus accumbens, and mediodorsal thalamic nucleus: Roles in a fear-based context discrimination task. Neurobiology of Learning and Memory, 85(1), 71–85. https://doi.org/10.1016/j.nlm.2005.08.011
  • Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., Harris, M. A., Hill, D. P., Issel-Tarver, L., Kasarskis, A., Lewis, S., Matese, J. C., Richardson, J. E., Ringwald, M., Rubin, G. M., and Sherlock, G. (2000). Gene ontology: Tool for the unification of biology. In Nature Genetics (Vol. 25, Issue 1, pp. 25–29). https://doi.org/10.1038/75556
  • Ashwell, R., and Ito, R. (2014). Excitotoxic lesions of the infralimbic, but not prelimbic cortex facilitate reversal of appetitive discriminative context conditioning: The role of the infralimbic cortex in context generalization. Frontiers in Behavioral Neuroscience, 8(FEB). https://doi.org/10.3389/fnbeh.2014.00063
  • Bahari-Javan, S., Sananbenesi, F., and Fischer, A. (2014). Histone-acetylation: a link between Alzheimer's disease and post-traumatic stress disorder?. Frontiers in neuroscience, 8, 160. https://doi.org/10.3389/fnins.2014.00160
  • Barrett, T., Suzek, T. O., Troup, D. B., Wilhite, S. E., Ngau, W.-C., Ledoux, P., Rudnev, D., Lash, A. E., Fujibuchi, W., and Edgar, R. (2005). NCBI GEO: mining millions of expression profiles—database and tools. Nucleic Acids Research, 33(suppl_1), D562–D566.
  • Belzung, C., Turiault, M., and Griebel, G. (2014). Optogenetics to study the circuits of fear- and depression-like behaviors: a critical analysis. Pharmacology, biochemistry, and behavior, 122, 144–157. https://doi.org/10.1016/j.pbb.2014.04.002
  • Bisson, J. I., Roberts, N. P., Andrew, M., Cooper, R., and Lewis, C. (2013). Psychological therapies for chronic post-traumatic stress disorder (PTSD) in adults. The Cochrane database of systematic reviews, 2013(12), CD003388. https://doi.org/10.1002/14651858.CD003388.pub4
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Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler ve Yeniden Konumlandırılan İlaçlar

Yıl 2023, Cilt: 23 Sayı: 2, 532 - 546, 03.05.2023

Elıf Kubat Oktem

https://doi.org/10.35414/akufemubid.1173072

Öz

Travma sonrası stres bozukluğu (TSSB), fiziksel hasar veya kaygı gibi zihinsel şok içeren bir kazayı takiben
görülen travmanın neden olduğu zihinsel bir hastalıktır. Toplumda yaygın olmasına rağmen, TSSB'nin
prognozu ve optimal terapötikleri sınırlıdır. Erken müdahale için moleküler hedefler belirsiz kaldığından,
daha iyi bir TSSB patogenezinin moleküler temellerinin anlaşılması hastalık prognozunun zorluklarını
karşılamak ve bu moleküler hedeflere yönelik teşhis ve tedavi için gereklidir. Strese maruz bırakılan
farelerin iki farklı dokusundan elde edilen mikrodizi verilerinin işlenmesi ve analiziyle yapılan bu
çalışmada, her iki tip doku için de anlatımı farklılık gösteren genler tespit edilmiş, bu genlerin
zenginleştiği yolizleri bulunmuş, bu genlerin protein protein etkileşim ağları ve bu ağlardaki hub
proteinler tespit edilmiştir. Bu hastalıkta anlatımı farklılık gösteren genlerin etkilerini tersini çevirmeye
yönelik her iki farklı tip doku için de ayrı ayrı yapılan ilaç yeniden konumlandırma çalışmalarının
karşılaştırılması sonucunda; vorinostat, homoharringtonin ve QL-XII-47 TSSB’yi iyileştirmek için yeni ilaç
adayları olarak önerilmiştir. Bu ilaçlardan vorinostat’ın, hücrede HDAC1, HDAC2, HDAC3, HDAC6, HDAC7
ve HDAC8 genlerini hedef aldığı tespit edilmiştir.

Anahtar Kelimeler

TSSB Travma sonrası stres bozukluğu biyoinformatik ilaç yeniden konumlandırma sistem biyolojisi

Kaynakça

  • Adshead, G. (2000). Psychological therapies for post-traumatic stress disorder. The British Journal of Psychiatry, 177, 144–148.
  • Albrechet-Souza, L., Carvalho, M. C., and Brandão, M. L. (2013). D1-like receptors in the nucleus accumbens shell regulate the expression of contextual fear conditioning and activity of the anterior cingulate cortex in rats. International Journal of Neuropsychopharmacology, 16(5), 1045–1057. https://doi.org/10.1017/S146114571200082X
  • Alvandi, F., Kwitkowski, V. E., Ko, C. W., Rothmann, M. D., Ricci, S., Saber, H., Ghosh, D., Brown, J., Pfeiler, E., Chikhale, E., Grillo, J., Bullock, J., Kane, R., Kaminska, E., Farrell, A. T., and Pazdur, R. (2014). U.S. food and drug administration approval summary: omacetaxine mepesuccinate as treatment for chronic myeloid leukemia. Oncologist, 19, 94–99.
  • Antoniadis, E. A., and McDonald, R. J. (2006). Fornix, medial prefrontal cortex, nucleus accumbens, and mediodorsal thalamic nucleus: Roles in a fear-based context discrimination task. Neurobiology of Learning and Memory, 85(1), 71–85. https://doi.org/10.1016/j.nlm.2005.08.011
  • Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., Harris, M. A., Hill, D. P., Issel-Tarver, L., Kasarskis, A., Lewis, S., Matese, J. C., Richardson, J. E., Ringwald, M., Rubin, G. M., and Sherlock, G. (2000). Gene ontology: Tool for the unification of biology. In Nature Genetics (Vol. 25, Issue 1, pp. 25–29). https://doi.org/10.1038/75556
  • Ashwell, R., and Ito, R. (2014). Excitotoxic lesions of the infralimbic, but not prelimbic cortex facilitate reversal of appetitive discriminative context conditioning: The role of the infralimbic cortex in context generalization. Frontiers in Behavioral Neuroscience, 8(FEB). https://doi.org/10.3389/fnbeh.2014.00063
  • Bahari-Javan, S., Sananbenesi, F., and Fischer, A. (2014). Histone-acetylation: a link between Alzheimer's disease and post-traumatic stress disorder?. Frontiers in neuroscience, 8, 160. https://doi.org/10.3389/fnins.2014.00160
  • Barrett, T., Suzek, T. O., Troup, D. B., Wilhite, S. E., Ngau, W.-C., Ledoux, P., Rudnev, D., Lash, A. E., Fujibuchi, W., and Edgar, R. (2005). NCBI GEO: mining millions of expression profiles—database and tools. Nucleic Acids Research, 33(suppl_1), D562–D566.
  • Belzung, C., Turiault, M., and Griebel, G. (2014). Optogenetics to study the circuits of fear- and depression-like behaviors: a critical analysis. Pharmacology, biochemistry, and behavior, 122, 144–157. https://doi.org/10.1016/j.pbb.2014.04.002
  • Bisson, J. I., Roberts, N. P., Andrew, M., Cooper, R., and Lewis, C. (2013). Psychological therapies for chronic post-traumatic stress disorder (PTSD) in adults. The Cochrane database of systematic reviews, 2013(12), CD003388. https://doi.org/10.1002/14651858.CD003388.pub4
  • Carbon, S., Douglass, E., Good, B. M., Unni, D. R., Harris, N. L., Mungall, C. J., Basu, S., Chisholm, R. L., Dodson, R. J., Hartline, E., Fey, P., Thomas, P. D., Albou, L. P., Ebert, D., Kesling, M. J., Mi, H., Muruganujan, A., Huang, X., Mushayahama, T., … Elser, J. (2021). The Gene Ontology resource: Enriching a GOld mine. Nucleic Acids Research, 49(D1),D325–D334. https://doi.org/10.1093/nar/gkaa1113
  • Chen, Y. T., Xie, J. Y., Sun, Q., and Mo, W. J. (2019). Novel drug candidates for treating esophageal carcinoma: A study on differentially expressed genes, using connectivity mapping and molecular docking. International Journal of Oncology, 54(1), 152–166. https://doi.org/10.3892/ijo.2018.4618
  • Chin, C.-H., Chen, S.-H., Wu, H.-H., Ho, C.-W., Ko, M.-T., and Lin, C.-Y. (2014). cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Systems Biology, 8 Suppl 4(Suppl 4), S11. https://doi.org/10.1186/1752-0509-8-S4-S11
  • Cho, J. H. , Lee, I. , Hammamieh, R. , Wang, K. , Baxter, D. , Scherler, K. , Etheridge, A. , Kulchenko, A. , Gautam, A. , Muhie, S. , Chakraborty, N. , Galas, D. J. , Jett, M. , and ood, L. (2014). Molecular evidence of stress-induced acute heart injury in a mouse model simulating posttraumatic stress disorder. Proceedings of the National Academy of Sciences of the United States of America, 111(8), 3188–3193.
  • Craddock, T. J. A., Harvey, J. M., Nathanson, L., Barnes, Z. M., Klimas, N. G., Fletcher, M. A., and Broderick, G. (2015). Using gene expression signatures to identify novel treatment strategies in gulf war illness. BMC Medical Genomics, 8(1). https://doi.org/10.1186/s12920-015-0111-3 Daskalakis, N. P., Cohen, H., Cai, G., Buxbaum, J. D., and Yehuda, R. (2014). Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes. PNAS, 111(37), 13529–13534. https://doi.org/10.1073/pnas.1401660111
  • Fabregat, A., Sidiropoulos, K., Garapati, P., Gillespie, M., Hausmann, K., Haw, R., Jassal, B., Jupe, S., Korninger, F., McKay, S., Matthews, L., May, B., Milacic, M., Rothfels, K., Shamovsky, V., Webber, M., Weiser, J., Williams, M., Wu, G., … D’Eustachio, P. (2016). The Reactome pathway Knowledgebase. Nucleic Acids Research, 44(D1), D481-7. https://doi.org/10.1093/nar/gkv1351
  • Gasparyan, A., Navarro, D., Navarrete, F., and Manzanares, J. (2022). Pharmacological strategies for post-traumatic stress disorder (PTSD): From animal to clinical studies. Neuropharmacology, 218, 109211. https://doi.org/10.1016/j.neuropharm.2022.109211
  • Grover, M. P., Ballouz, S., Mohanasundaram, K. A., George, R. A., Goscinski, A., Crowley, T. M., Sherman, C. D. H., and Wouters, M. A. (2015). Novel therapeutics for coronary artery disease from genome-wide association study data. BMC Medical Genomics, 8(2). https://doi.org/10.1186/1755-8794-8-S2-S1
  • Iribarren, J., Prolo, P., Neagos, N., and Chiappelli, F. (2005). Post-Traumatic Stress Disorder: Evidence-Based Research for the Third Millennium. ECAM, 2(4), 503–512. https://doi.org/10.1093/ecam/neh127
  • Jovanovic, T., Sakoman, A. J., Kozarić-Kovačić, D., Meštrović, A. H., Duncan, E. J., Davis, M., and Norrholm, S. D. (2013). Acute stress disorder versus chronic posttraumatic stress disorder: inhibition of fear as a function of time since trauma. Depression and anxiety, 30(3), 217–224. https://doi.org/10.1002/da.21991
  • Kamburov, A., Pentchev, K., Galicka, H., Wierling, C., Lehrach, H., and Herwig, R. (2011). ConsensusPathDB: Toward a more complete picture of cell biology. Nucleic Acids Research, 39(SUPPL. 1). https://doi.org/10.1093/nar/gkq1156
  • Kanehisa, M., Araki, M., Goto, S., Hattori, M., Hirakawa, M., Itoh, M., Katayama, T., Kawashima, S., Okuda, S., Tokimatsu, T., and Yamanishi, Y. (2008). KEGG for linking genomes to life and the environment. Nucleic Acids Research, 36 (Database issue), D480-4. https://doi.org/10.1093/nar/gkm882
  • Kang, H. K., Natelson, B. H., Mahan, C. M., Lee, K. Y., and Murphy, F. M. (2003). Post-Traumatic Stress Disorder and Chronic Fatigue Syndrome-like Illness among Gulf War Veterans: A Population-based Survey of 30,000 Veterans. American Journal of Epidemiology, 157(2), 141–148. https://doi.org/10.1093/aje/kwf187
  • Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime Prevalence and Age-of-Onset Distributions of DSM-IV Disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):593–602. doi:10.1001/archpsyc.62.6.593 Kibler, J. L. (2009). Posttraumatic stress and cardiovascular disease risk. Journal of Trauma and Dissociation, 10(2), 135–150. https://doi.org/10.1080/15299730802624577
  • Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., Li, Q., Shoemaker, B. A., Thiessen, P. A., Yu, B., Zaslavsky, L., Zhang, J., and Bolton, E. E. (2019). PubChem 2019 update: Improved access to chemical data. Nucleic Acids Research, 47(D1), D1102–D1109. https://doi.org/10.1093/nar/gky1033
  • Kubzansky, L. D., and Koenen, K. C. (2009). Is posttraumatic stress disorder related to development of heart disease? An update. Cleveland Clinic Journal of Medicine, 76(SUPPL.2). https://doi.org/10.3949/ccjm.76.s2.12
  • KV, A., Madhana, R. M., JS, I. C., Lahkar, M., Sinha, S., and Naidu, V. G. M. (2018). Antidepressant activity of vorinostat is associated with amelioration of oxidative stress and inflammation in a corticosterone-induced chronic stress model in mice. Behavioural Brain Research, 344, 73–84. https://doi.org/10.1016/j.bbr.2018.02.009
  • Lee, D.-H. ;, Lee, J.-Y. ;, Hong, D.-Y. ;, Lee, E.-C. ;, Park, S.-W. ;, and Lee. (2022). Neuroinflammation in Post-Traumatic Stress Disorder. Biomedicines, 10, 953. https://doi.org/10.3390/biomedicines10050953
  • Maddox, S. A., Schafe, G. E., and Ressler, K. J. (2013). Exploring epigenetic regulation of fear memory and biomarkers associated with post-traumatic stress disorder. Frontiers in Psychiatry, 4(JUL). https://doi.org/10.3389/fpsyt.2013.00062
  • Matsumoto, Y., Morinobu, S., Yamamoto, S., Matsumoto, T., Takei, S., Fujita, Y., and Yamawaki, S. (2013). Vorinostat ameliorates impaired fear extinction possibly via the hippocampal NMDA-CaMKII pathway in an animal model of posttraumatic stress disorder. Psychopharmacology, 229(1), 51–62. https://doi.org/10.1007/s00213-013-3078-9
  • Mudunuri, U., Che, A., Yi, M., and Stephens, R. M. (2009). bioDBnet: The biological database network. Bioinformatics, 25(4), 555–556. https://doi.org/10.1093/bioinformatics/btn654
  • Muhie, S., Gautam, A., Chakraborty, N., Hoke, A., Meyerhoff, J., Hammamieh, R., and Jett, M. (2017). Molecular indicators of stress-induced neuroinflammation in a mouse model simulating features of post-traumatic stress disorder. Translational Psychiatry, 7(5), e1135. https://doi.org/10.1038/tp.2017.91
  • Muhie, S., Gautam, A., Meyerhoff, J., Chakraborty, N., Hammamieh, R., and Jett, M. (2015). Brain transcriptome profiles in mouse model simulating features of post-traumatic stress disorder. Molecular Brain, 8(1). https://doi.org/10.1186/s13041-015-0104-3
  • O’Donnell, M. L., Varker, T., Creamer, M., Fletcher, S., McFarlane, A. C., Silove, D., Bryant, R. A., and Forbes, D. (2013). Exploration of Delayed-Onset Posttraumatic Stress Disorder After Severe Injury. Psychosomatic Medicine, 75(1), 68–75. https://doi.org/10.1097/psy.0b013e3182761e8b
  • Öktem, E. K., Yazar, M., Gulfidan, G., and Arga, K. Y. (2019). Cancer Drug Repositioning by Comparison of Gene Expression in Humans and Axolotl (Ambystoma mexicanum) During Wound Healing. OMICS A Journal of Integrative Biology, 23(8), 389–405. https://doi.org/10.1089/omi.2019.0093
  • Oughtred, R., Stark, C., Breitkreutz, B.-J., Rust, J., Boucher, L., Chang, C., Kolas, N., O’Donnell, L., Leung, G., and McAdam, R. (2019). The BioGRID interaction database: 2019 update. Nucleic Acids Research, 47(D1), D529–D541.
  • Pedersen, S. S., Middel, B., and Larsen, M. L. (2003). Posttraumatic stress disorder in first-time myocardial infarction patients. Heart and Lung: Journal of Acute and Critical Care, 32(5), 300–307. https://doi.org/10.1016/S0147-9563(03)00097-9
  • Règue, M., Poilbout, C., Martin, V., Franc, B., Lanfumey, L., and Mongeau, R. (2019). Increased 5-HT2C receptor editing predisposes to PTSD-like behaviors and alters BDNF and cytokines signaling. Translational Psychiatry, 9(1). https://doi.org/10.1038/s41398-019-0431-8
  • Roder, C., and Thomson, M. J. (2015). Auranofin: Repurposing an Old Drug for a Golden New Age. Drugs in R and D, 15(1), 13–20. https://doi.org/10.1007/s40268-015-0083-y
  • Rosenfield, P. J., Stratyner, A., Tufekcioglu, S., Karabell, S., McKelvey, J., and Litt, L. (2018). Complex PTSD in ICD-11: A Case Report on a New Diagnosis. Journal of Psychiatric Practice, 24(5), 364–370. https://doi.org/10.1097/PRA.0000000000000327
  • Sean, D., and Meltzer, P. S. (2007). GEOquery: A bridge between the Gene Expression Omnibus (GEO) and BioConductor. Bioinformatics, 23(14), 1846–1847. https://doi.org/10.1093/bioinformatics/btm254
  • Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., and Ideker, T. (2003). Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Research, 13(11), 2498–2504. https://doi.org/10.1101/gr.1239303
  • Smyth, G. K., Ritchie, M., Thorne, N., and Wettenhall, J. (2005). LIMMA: linear models for microarray data. In Bioinformatics and Computational Biology Solutions Using R and Bioconductor. Statistics for Biology and Health.
  • Stein, D. J., McLaughlin, K. A., Koenen, K. C., Atwoli, L., Friedman, M. J., Hill, E. D., Maercker, A., Petukhova, M., Shahly, V., van Ommeren, M., Alonso, J., Borges, G., de Girolamo, G., de Jonge, P., Demyttenaere, K., Florescu, S., Karam, E. G., Kawakami, N., Matschinger, H., Okoliyski, M., … Kessler, R. C. (2014). DSM-5 and ICD-11 definitions of posttraumatic stress disorder: investigating "narrow" and "broad" approaches. Depression and anxiety, 31(6), 494–505. https://doi.org/10.1002/da.22279
  • Szklarczyk, D., Santos, A., von Mering, C., Jensen, L. J., Bork, P., and Kuhn, M. (2016). STITCH 5: Augmenting protein-chemical interaction networks with tissue and affinity data. Nucleic Acids Research, 44(D1), D380–D384. https://doi.org/10.1093/nar/gkv1277
  • Turanli, B., Karagoz, K., Bidkhori, G., Sinha, R., Gatza, M. L., Uhlen, M., Mardinoglu, A., and Arga, K. Y. (2019). Multi-omic data interpretation to repurpose subtype specific drug candidates for breast cancer. Frontiers in Genetics, 10(MAY). https://doi.org/10.3389/fgene.2019.00420
  • Turanli, B., Zhang, C., Kim, W., Benfeitas, R., Uhlen, M., Arga, K. Y., and Mardinoglu, A. (2019). Discovery of therapeutic agents for prostate cancer using genome-scale metabolic modeling and drug repositioning. EBioMedicine, 42, 386–396. https://doi.org/10.1016/j.ebiom.2019.03.009
  • van Loey, N. E., van de Schoot, R., and Faber, A. W. (2012). Posttraumatic Stress Symptoms after Exposure to Two Fire Disasters: Comparative Study. PLoS ONE , 6(7), e41532. https://doi.org/10.1371/journal.pone.0041532
  • Vogrinc, D., and Kunej, T. (2017). Drug repositioning: computational approaches and research examples classified according to the evidence level. Discoveries, 5(2), e75. https://doi.org/10.15190/d.2017.5
  • von Känel, R., Hari, R., Schmid, J. P., Wiedemar, L., Guler, E., Barth, J., Saner, H., Schnyder, U., and Begré, S. (2011). Non-fatal cardiovascular outcome in patients with posttraumatic stress symptoms caused by myocardial infarction. Journal of Cardiology, 58(1), 61–68. https://doi.org/10.1016/j.jjcc.2011.02.007
  • Wawruszak, A., Borkiewicz, L., Okon, E., Kukula-Koch, W., Afshan, S., and Halasa, M. (2021). Vorinostat (SAHA) and breast cancer: An overview. Cancers, 13(18). https://doi.org/10.3390/cancers13184700
  • Xu, R., and Wang, Q. Q. (2016). A genomics-based systems approach towards drug repositioning for rheumatoid arthritis. BMC Genomics, 17. https://doi.org/10.1186/s12864-016-2910-0
  • Xue, C., Ge, Y., Tang, B., Liu, Y., Kang, P., Wang, M., and Zhang, L. (2015). A meta-analysis of risk factors for combat-related PTSD among military personnel and veterans. PLoS ONE, 10(3). https://doi.org/10.1371/journal.pone.0120270
  • Yakhni, M., Briat, A., el Guerrab, A., Furtado, L., Kwiatkowski, F., Miot-Noirault, E., Cachin, F., Penault-Llorca, F., and Radosevic-Robin, N. (2019). Homoharringtonine, an approved anti-leukemia drug, suppresses triple negative breast cancer growth through a rapid reduction of anti-apoptotic protein abundance. American Journal of Cancer Research, 9(5), 1043–1060.
  • Zhang, M., Luo, H., Xi, Z., and Rogaeva, E. (2015). Drug repositioning for diabetes based on “omics” data mining. PLoS ONE, 10(5). https://doi.org/10.1371/journal.pone.0126082
Toplam 55 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Mühendislik
Bölüm Makaleler
Yazarlar

Elıf Kubat Oktem 0000-0003-0913-8527

Erken Görünüm Tarihi 28 Nisan 2023
Yayımlanma Tarihi 3 Mayıs 2023
Gönderilme Tarihi 9 Eylül 2022
Yayımlandığı Sayı Yıl 2023 Cilt: 23 Sayı: 2

Kaynak Göster

APA Kubat Oktem, E. (2023). Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler ve Yeniden Konumlandırılan İlaçlar. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, 23(2), 532-546. https://doi.org/10.35414/akufemubid.1173072
AMA Kubat Oktem E. Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler ve Yeniden Konumlandırılan İlaçlar. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. Mayıs 2023;23(2):532-546. doi:10.35414/akufemubid.1173072
Chicago Kubat Oktem, Elıf. “Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler Ve Yeniden Konumlandırılan İlaçlar”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 23, sy. 2 (Mayıs 2023): 532-46. https://doi.org/10.35414/akufemubid.1173072.
EndNote Kubat Oktem E (01 Mayıs 2023) Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler ve Yeniden Konumlandırılan İlaçlar. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 23 2 532–546.
IEEE E. Kubat Oktem, “Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler ve Yeniden Konumlandırılan İlaçlar”, Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, c. 23, sy. 2, ss. 532–546, 2023, doi: 10.35414/akufemubid.1173072.
ISNAD Kubat Oktem, Elıf. “Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler Ve Yeniden Konumlandırılan İlaçlar”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi 23/2 (Mayıs 2023), 532-546. https://doi.org/10.35414/akufemubid.1173072.
JAMA Kubat Oktem E. Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler ve Yeniden Konumlandırılan İlaçlar. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2023;23:532–546.
MLA Kubat Oktem, Elıf. “Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler Ve Yeniden Konumlandırılan İlaçlar”. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi, c. 23, sy. 2, 2023, ss. 532-46, doi:10.35414/akufemubid.1173072.
Vancouver Kubat Oktem E. Travma Sonrası Stres Bozukluğu (TSSB) Tedavisine Yönelik Moleküler Hedefler ve Yeniden Konumlandırılan İlaçlar. Afyon Kocatepe Üniversitesi Fen Ve Mühendislik Bilimleri Dergisi. 2023;23(2):532-46.
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