Inflammation impacts androgen receptor signaling in basal prostate stem cells through interleukin 1 receptor antagonist.

Male Animals Receptors, Androgen / metabolism Prostate / metabolism Mice Signal Transduction Stem Cells / metabolism Interleukin 1 Receptor Antagonist Protein / metabolism Mice, Transgenic Inflammation / metabolism Humans Prostatitis / metabolism Cell Differentiation Prostatic Hyperplasia / metabolism Cell Proliferation

Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
25 Oct 2024
Historique:
received: 04 12 2023
accepted: 14 10 2024
medline: 26 10 2024
pubmed: 26 10 2024
entrez: 25 10 2024
Statut: epublish

Résumé

Chronic prostate inflammation in patients with benign prostate hyperplasia (BPH) correlates with the severity of symptoms. How inflammation contributes to prostate enlargement and/or BPH symptoms and the underlying mechanisms remain unclear. In this study, we utilize a unique transgenic mouse model that mimics chronic non-bacterial prostatitis in men and investigate the impact of inflammation on androgen receptor (AR) in basal prostate stem cells (bPSC) and their differentiation in vivo. We find that inflammation significantly enhances AR levels and activity in bPSC. More importantly, we identify interleukin 1 receptor antagonist (IL-1RA) as a crucial regulator of AR in bPSC during inflammation. IL-1RA is one of the top molecules upregulated by inflammation, and inhibiting IL-1RA reverses the enhanced AR activity in organoids derived from inflamed bPSC. Additionally, IL-1RA appears to activate AR by counteracting IL-1α's inhibitory effect. Furthermore, using a lineage tracing model, we observe that inflammation induces bPSC proliferation and differentiation into luminal cells even under castrate conditions, indicating that AR activation driven by inflammation is sufficient to promote bPSC proliferation and differentiation. Taken together, our study uncovers mechanisms through which inflammation modulates AR signaling in bPSC and induces bPSC luminal differentiation that may contribute to prostate hyperplasia.

Identifiants

DOI: 10.1038/s42003-024-07071-y PMID: 39455902
pubmed: 39455902
doi: 10.1038/s42003-024-07071-y
pii: 10.1038/s42003-024-07071-y
doi:

Substances chimiques

Receptors, Androgen 0
Interleukin 1 Receptor Antagonist Protein 0
AR protein, mouse 0
Il1rn protein, mouse 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1390

Subventions

Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01DK084454
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R01DK126478

Informations de copyright

© 2024. The Author(s).

Références

Gandaglia, G. et al. The role of prostatic inflammation in the development and progression of benign and malignant diseases. Curr. Opin. Urol. 27, 99–106 (2017).
pubmed: 27906778 doi: 10.1097/MOU.0000000000000369
De Nunzio, C., Presicce, F. & Tubaro, A. Inflammatory mediators in the development and progression of benign prostatic hyperplasia. Nat. Rev. Urol. 13, 613–626 (2016).
pubmed: 27686153 doi: 10.1038/nrurol.2016.168
Nickel, J. C. et al. The relationship between prostate inflammation and lower urinary tract symptoms: examination of baseline data from the REDUCE trial. Eur. Urol. 54, 1379–1384 (2008).
pubmed: 18036719 doi: 10.1016/j.eururo.2007.11.026
Robert, G. et al. Inflammation in benign prostatic hyperplasia: a 282 patients’ immunohistochemical analysis. Prostate 69, 1774–1780 (2009).
pubmed: 19670242 pmcid: 2833181 doi: 10.1002/pros.21027
Lawson, D. A. et al. Basal epithelial stem cells are efficient targets for prostate cancer initiation. Proc. Natl. Acad. Sci. USA 107, 2610–2615 (2010).
pubmed: 20133806 pmcid: 2823887 doi: 10.1073/pnas.0913873107
Crowell, P. D. et al. Expansion of luminal progenitor cells in the aging mouse and human prostate. Cell Rep. 28, 1499–1510.e1496 (2019).
pubmed: 31390564 pmcid: 6710009 doi: 10.1016/j.celrep.2019.07.007
Toivanen, R., Mohan, A. & Shen, M. M. Basal progenitors contribute to repair of the prostate epithelium following induced luminal anoikis. Stem Cell Rep. 6, 660–667 (2016).
doi: 10.1016/j.stemcr.2016.03.007
Xie, Q. et al. Dissecting cell-type-specific roles of androgen receptor in prostate homeostasis and regeneration through lineage tracing. Nat. Commun. 8, 14284 (2017).
pubmed: 28112153 pmcid: 5264212 doi: 10.1038/ncomms14284
Karthaus, W. R. et al. Regenerative potential of prostate luminal cells revealed by single-cell analysis. Science 368, 497–505 (2020).
pubmed: 32355025 pmcid: 7313621 doi: 10.1126/science.aay0267
Haverkamp, J. M. et al. An inducible model of abacterial prostatitis induces antigen specific inflammatory and proliferative changes in the murine prostate. Prostate 71, 1139–1150 (2011).
pubmed: 21656824 pmcid: 3136647 doi: 10.1002/pros.21327
Kwon, O. J., Zhang, L. & Xin, L. Stem cell antigen-1 identifies a distinct androgen-independent murine prostatic luminal cell lineage with bipotent potential. Stem Cells 34, 191–202 (2016).
pubmed: 26418304 doi: 10.1002/stem.2217
Wang, H. H. et al. Characterization of autoimmune inflammation induced prostate stem cell expansion. Prostate 75, 1620–1631 (2015).
pubmed: 26174474 pmcid: 4720918 doi: 10.1002/pros.23043
Kwon, O. J., Zhang, L., Ittmann, M. M. & Xin, L. Prostatic inflammation enhances basal-to-luminal differentiation and accelerates initiation of prostate cancer with a basal cell origin. Proc. Natl. Acad. Sci. USA 111, E592–E600 (2014).
pubmed: 24367088 doi: 10.1073/pnas.1318157111
Wang, L. et al. Expansion of prostate epithelial progenitor cells after inflammation of the mouse prostate. Am. J. Physiol. Ren. Physiol. 308, F1421–F1430 (2015).
doi: 10.1152/ajprenal.00488.2014
Xin, L., Lukacs, R. U., Lawson, D. A., Cheng, D. & Witte, O. N. Self-renewal and multilineage differentiation in vitro from murine prostate stem cells. Stem Cells 25, 2760–2769 (2007).
pubmed: 17641240 doi: 10.1634/stemcells.2007-0355
Henry, G. H. et al. A cellular anatomy of the normal adult human prostate and prostatic urethra. Cell Rep. 25, 3530–3542.e3535 (2018).
pubmed: 30566875 pmcid: 6411034 doi: 10.1016/j.celrep.2018.11.086
Gao, N. et al. The role of hepatocyte nuclear factor-3 alpha (Forkhead Box A1) and androgen receptor in transcriptional regulation of prostatic genes. Mol. Endocrinol. 17, 1484–1507 (2003).
pubmed: 12750453 doi: 10.1210/me.2003-0020
Lupien, M. et al. FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription. Cell 132, 958–970 (2008).
pubmed: 18358809 pmcid: 2323438 doi: 10.1016/j.cell.2008.01.018
Jozwik, K. M. & Carroll, J. S. Pioneer factors in hormone-dependent cancers. Nat. Rev. Cancer 12, 381–385 (2012).
pubmed: 22555282 doi: 10.1038/nrc3263
Sato, N. et al. Androgenic induction of prostate-specific antigen gene is repressed by protein-protein interaction between the androgen receptor and AP-1/c-Jun in the human prostate cancer cell line LNCaP. J. Biol. Chem. 272, 17485–17494 (1997).
pubmed: 9211894 doi: 10.1074/jbc.272.28.17485
Lin-Tsai, O. et al. Surgical intervention for symptomatic benign prostatic hyperplasia is correlated with expression of the AP-1 transcription factor network. Prostate 74, 669–679 (2014).
pubmed: 24500928 pmcid: 4160824 doi: 10.1002/pros.22785
Thiel, G., Welck, J., Wissenbach, U. & Rossler, O. G. Dihydrotestosterone activates AP-1 in LNCaP prostate cancer cells. Int. J. Biochem. Cell Biol. 110, 9–20 (2019).
pubmed: 30794859 doi: 10.1016/j.biocel.2019.02.005
Tang, F. et al. Chromatin profiles classify castration-resistant prostate cancers suggesting therapeutic targets. Science 376, eabe1505 (2022).
pubmed: 35617398 pmcid: 9299269 doi: 10.1126/science.abe1505
Wei, X. et al. Spatially restricted stromal wnt signaling restrains prostate epithelial progenitor growth through direct and indirect mechanisms. Cell Stem Cell 24, 753–768.e756 (2019).
pubmed: 30982770 pmcid: 6548441 doi: 10.1016/j.stem.2019.03.010
Bisson, I. & Prowse, D. M. WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics. Cell Res. 19, 683–697 (2009).
pubmed: 19365403 doi: 10.1038/cr.2009.43
Mohyeldin, A., Garzon-Muvdi, T. & Quinones-Hinojosa, A. Oxygen in stem cell biology: a critical component of the stem cell niche. Cell Stem Cell 7, 150–161 (2010).
pubmed: 20682444 doi: 10.1016/j.stem.2010.07.007
Mazumdar, J. et al. O2 regulates stem cells through Wnt/beta-catenin signalling. Nat. Cell Biol. 12, 1007–1013 (2010).
pubmed: 20852629 pmcid: 3144143 doi: 10.1038/ncb2102
Culig, Z. et al. Interleukin 1beta mediates the modulatory effects of monocytes on LNCaP human prostate cancer cells. Br. J. Cancer 78, 1004–1011 (1998).
pubmed: 9792142 pmcid: 2063143 doi: 10.1038/bjc.1998.619
Staverosky, J. A., Zhu, X. H., Ha, S. & Logan, S. K. Anti-androgen resistance in prostate cancer cells chronically induced by interleukin-1beta. Am. J. Clin. Exp. Urol. 1, 53–65 (2013).
pubmed: 25374900 pmcid: 4219287
Chang, M. A. et al. IL-1beta induces p62/SQSTM1 and represses androgen receptor expression in prostate cancer cells. J. Cell Biochem. 115, 2188–2197 (2014).
pubmed: 25103771 pmcid: 4517682 doi: 10.1002/jcb.24897
Thomas-Jardin, S. E. et al. RELA is sufficient to mediate interleukin-1 repression of androgen receptor expression and activity in an LNCaP disease progression model. Prostate 80, 133–145 (2020).
pubmed: 31730277 doi: 10.1002/pros.23925
Muzumdar, M. D., Tasic, B., Miyamichi, K., Li, L. & Luo, L. A global double-fluorescent Cre reporter mouse. Genesis 45, 593–605 (2007).
pubmed: 17868096 doi: 10.1002/dvg.20335
Crowley, L. & Shen, M. M. Heterogeneity and complexity of the prostate epithelium: new findings from single-cell RNA sequencing studies. Cancer Lett. 525, 108–114 (2022).
pubmed: 34728312 doi: 10.1016/j.canlet.2021.10.035
Zhang, B. et al. Non-cell-autonomous regulation of prostate epithelial homeostasis by androgen receptor. Mol. Cell 63, 976–989 (2016).
pubmed: 27594448 pmcid: 5026614 doi: 10.1016/j.molcel.2016.07.025
Gabay, C., Porter, B., Fantuzzi, G. & Arend, W. P. Mouse IL-1 receptor antagonist isoforms: complementary DNA cloning and protein expression of intracellular isoform and tissue distribution of secreted and intracellular IL-1 receptor antagonist in vivo. J. Immunol. 159, 5905–5913 (1997).
pubmed: 9550387 doi: 10.4049/jimmunol.159.12.5905
Martin, P. et al. Intracellular IL-1 receptor antagonist isoform 1 released from keratinocytes upon cell death acts as an inhibitor for the alarmin IL-1alpha. J. Immunol. 204, 967–979 (2020).
pubmed: 31932497 doi: 10.4049/jimmunol.1901074
Watson, J. M. et al. The intracellular IL-1 receptor antagonist alters IL-1-inducible gene expression without blocking exogenous signaling by IL-1 beta. J. Immunol. 155, 4467–4475 (1995).
pubmed: 7594609 doi: 10.4049/jimmunol.155.9.4467
Vecile, E. et al. Intracellular function of interleukin-1 receptor antagonist in ischemic cardiomyocytes. PLoS ONE 8, e53265 (2013).
pubmed: 23308180 pmcid: 3540084 doi: 10.1371/journal.pone.0053265
Giavridis, T. et al. CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade. Nat. Med. 24, 731–738 (2018).
pubmed: 29808005 pmcid: 6410714 doi: 10.1038/s41591-018-0041-7
Gander-Bui, H. T. T. et al. Targeted removal of macrophage-secreted interleukin-1 receptor antagonist protects against lethal Candida albicans sepsis. Immunity 56, 1743–1760 e1749 (2023).
pubmed: 37478856 doi: 10.1016/j.immuni.2023.06.023
Lee, S. O., Lou, W., Hou, M., Onate, S. A. & Gao, A. C. Interleukin-4 enhances prostate-specific antigen expression by activation of the androgen receptor and Akt pathway. Oncogene 22, 7981–7988 (2003).
pubmed: 12970746 doi: 10.1038/sj.onc.1206735
Hobisch, A. et al. Interleukin-6 regulates prostate-specific protein expression in prostate carcinoma cells by activation of the androgen receptor. Cancer Res. 58, 4640–4645 (1998).
pubmed: 9788616
Culig, Z. et al. Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor. Cancer Res. 54, 5474–5478 (1994).
pubmed: 7522959
Koryakina, Y., Ta, H. Q. & Gioeli, D. Androgen receptor phosphorylation: biological context and functional consequences. Endocr. Relat. Cancer 21, T131–T145 (2014).
pubmed: 24424504 pmcid: 4437516 doi: 10.1530/ERC-13-0472
Willder, J. M. et al. Androgen receptor phosphorylation at serine 515 by Cdk1 predicts biochemical relapse in prostate cancer patients. Br. J. Cancer 108, 139–148 (2013).
pubmed: 23321516 doi: 10.1038/bjc.2012.480
Ponguta, L. A., Gregory, C. W., French, F. S. & Wilson, E. M. Site-specific androgen receptor serine phosphorylation linked to epidermal growth factor-dependent growth of castration-recurrent prostate cancer. J. Biol. Chem. 283, 20989–21001 (2008).
pubmed: 18511414 pmcid: 2475695 doi: 10.1074/jbc.M802392200
Guo, Z. et al. Regulation of androgen receptor activity by tyrosine phosphorylation. Cancer Cell 10, 309–319 (2006).
pubmed: 17045208 doi: 10.1016/j.ccr.2006.08.021
Gioeli, D. et al. Androgen receptor phosphorylation. Regulation and identification of the phosphorylation sites. J. Biol. Chem. 277, 29304–29314 (2002).
pubmed: 12015328 doi: 10.1074/jbc.M204131200
Shahi, P., Seethammagari, M. R., Valdez, J. M., Xin, L. & Spencer, D. M. Wnt and Notch pathways have interrelated opposing roles on prostate progenitor cell proliferation and differentiation. Stem Cells 29, 678–688 (2011).
pubmed: 21308863 doi: 10.1002/stem.606
Lukacs, R. U., Goldstein, A. S., Lawson, D. A., Cheng, D. & Witte, O. N. Isolation, cultivation and characterization of adult murine prostate stem cells. Nat. Protoc. 5, 702–713 (2010).
pubmed: 20360765 pmcid: 2943378 doi: 10.1038/nprot.2010.11
Strand, D. W., Aaron, L., Henry, G., Franco, O. E. & Hayward, S. W. Isolation and analysis of discreet human prostate cellular populations. Differentiation 91, 139–151 (2016).
pubmed: 26546040 doi: 10.1016/j.diff.2015.10.013
Trapnell, C., Pachter, L. & Salzberg, S. L. TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25, 1105–1111 (2009).
pubmed: 19289445 pmcid: 2672628 doi: 10.1093/bioinformatics/btp120
Kim, D. et al. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, R36 (2013).
pubmed: 23618408 pmcid: 4053844 doi: 10.1186/gb-2013-14-4-r36
Anders, S., Pyl, P. T. & Huber, W. HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166–169 (2015).
pubmed: 25260700 doi: 10.1093/bioinformatics/btu638
Satija, R., Farrell, J. A., Gennert, D., Schier, A. F. & Regev, A. Spatial reconstruction of single-cell gene expression data. Nat. Biotechnol. 33, 495–502 (2015).
pubmed: 25867923 pmcid: 4430369 doi: 10.1038/nbt.3192
Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y. & Greenleaf, W. J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213–1218 (2013).
pubmed: 24097267 pmcid: 3959825 doi: 10.1038/nmeth.2688
Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754–1760 (2009).
pubmed: 19451168 pmcid: 2705234 doi: 10.1093/bioinformatics/btp324
Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).
pubmed: 19505943 pmcid: 2723002 doi: 10.1093/bioinformatics/btp352
Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576–589 (2010).
pubmed: 20513432 pmcid: 2898526 doi: 10.1016/j.molcel.2010.05.004
Kent, W. J., Zweig, A. S., Barber, G., Hinrichs, A. S. & Karolchik, D. BigWig and BigBed: enabling browsing of large distributed datasets. Bioinformatics 26, 2204–2207 (2010).
pubmed: 20639541 pmcid: 2922891 doi: 10.1093/bioinformatics/btq351
Kaya-Okur, H. S. et al. CUT&Tag for efficient epigenomic profiling of small samples and single cells. Nat. Commun. 10, 1930 (2019).
pubmed: 31036827 pmcid: 6488672 doi: 10.1038/s41467-019-09982-5
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
pubmed: 22388286 pmcid: 3322381 doi: 10.1038/nmeth.1923
Ramirez, F. et al. deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 44, W160–W165 (2016).
pubmed: 27079975 pmcid: 4987876 doi: 10.1093/nar/gkw257
Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1523 (2019).
pubmed: 30944313 pmcid: 6447622 doi: 10.1038/s41467-019-09234-6

Auteurs

Paula O Cooper (PO)

Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
Purdue Institute for Cancer Research, West Lafayette, IN, USA.
Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.
ORCID: 0000-0001-9201-1855

Jiang Yang (J)

Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA. yang1491@purdue.edu.
Purdue Institute for Cancer Research, West Lafayette, IN, USA. yang1491@purdue.edu.
ORCID: 0000-0002-2363-4810

Hsing-Hui Wang (HH)

Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
Purdue Institute for Cancer Research, West Lafayette, IN, USA.
Immune Monitoring and Genomics Facility, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

Meaghan M Broman (MM)

Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
Purdue Institute for Cancer Research, West Lafayette, IN, USA.

Shyaman Madhawa Jayasundara (SM)

Department of Computer Science, Purdue University, West Lafayette, IN, USA.
ORCID: 0000-0003-0522-3353

Subhransu Sekhar Sahoo (SS)

Department of Biochemistry, Purdue University, West Lafayette, IN, USA.

Bingyu Yan (B)

Department of Biochemistry, Purdue University, West Lafayette, IN, USA.

Gada D Awdalkreem (GD)

Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
Purdue Institute for Cancer Research, West Lafayette, IN, USA.

Gregory M Cresswell (GM)

Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
Purdue Institute for Cancer Research, West Lafayette, IN, USA.
Flow Cytometry Core Facility, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA.

Liang Wang (L)

Department of Pharmacology and Toxicology, Department of Urology, Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
ORCID: 0000-0002-4052-1316

Emery Goossens (E)

Department of Statistics, Purdue University, West Lafayette, IN, USA.

Nadia A Lanman (NA)

Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
Purdue Institute for Cancer Research, West Lafayette, IN, USA.
ORCID: 0000-0002-1819-7070

Rebecca W Doerge (RW)

Department of Statistics, Purdue University, West Lafayette, IN, USA.
Rensselaer Polytechnic Institute, Troy, NY, USA.

Faye Zheng (F)

Department of Statistics, Purdue University, West Lafayette, IN, USA.
Sorcero, Inc., Washington, DC, USA.

Liang Cheng (L)

Department of Pathology and Laboratory Medicine, Department of Surgery (Urology), Brown University Warren Alpert Medical School, the Legorreta Cancer Center at Brown University, and Brown University Health, Providence, RI, USA.
ORCID: 0000-0001-6049-5293

Saeed Alqahtani (S)

Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
Purdue Institute for Cancer Research, West Lafayette, IN, USA.

Scott A Crist (SA)

Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
Purdue Institute for Cancer Research, West Lafayette, IN, USA.
Carver College of Medicine, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA.

Robert E Braun (RE)

The Jackson Laboratory, Bar Harbor, ME, USA.
ORCID: 0000-0003-3856-9465

Majid Kazemian (M)

Purdue Institute for Cancer Research, West Lafayette, IN, USA.
Department of Computer Science, Purdue University, West Lafayette, IN, USA.
Department of Biochemistry, Purdue University, West Lafayette, IN, USA.
ORCID: 0000-0001-7080-8820

Travis J Jerde (TJ)

Department of Pharmacology and Toxicology, Department of Urology, Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA. tjjerde@iu.edu.
ORCID: 0009-0004-1561-5769

Timothy L Ratliff (TL)

Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA. tlratliff@purdue.edu.
Purdue Institute for Cancer Research, West Lafayette, IN, USA. tlratliff@purdue.edu.
ORCID: 0000-0003-4221-5416

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Inflammation impacts androgen receptor...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Récepteurs aux androgènes › Inflammation impacts androgen receptor...
questionsmedicales.fr › Tissus › Glandes exocrines › Prostate › Inflammation impacts androgen receptor...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Inflammation impacts androgen receptor...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Inflammation impacts androgen receptor...
questionsmedicales.fr › Cellules › Cellules souches › Inflammation impacts androgen receptor...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Antagoniste du récepteur à l'interleukine-1 › Inflammation impacts androgen receptor...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Inflammation impacts androgen receptor...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Inflammation impacts androgen receptor...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Inflammation impacts androgen receptor...
questionsmedicales.fr › Maladies urogénitales › Maladies urogénitales de l'homme › Maladies de l'appareil génital mâle › Maladies de la prostate › Prostatite › Inflammation impacts androgen receptor...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › Inflammation impacts androgen receptor...
questionsmedicales.fr › Maladies urogénitales › Maladies urogénitales de l'homme › Maladies de l'appareil génital mâle › Maladies de la prostate › Hyperplasie de la prostate › Inflammation impacts androgen receptor...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Inflammation impacts androgen receptor...