المؤلفون: Xing Li, Mingyu Liao, Jiangheng Guan, Ling Zhou, Rufei Shen, Min Long, Jiaqing Shao

المصدر: Diabetes & Metabolism Journal, Vol 46, Iss 3, Pp 451-463 (2022)

مصطلحات موضوعية: computational biology, diabetes mellitus, type 1, immune system, leukocytes, mononuclear, protein interaction maps, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Background The onset and progression of type 1 diabetes mellitus (T1DM) is closely related to autoimmunity. Effective monitoring of the immune system and developing targeted therapies are frontier fields in T1DM treatment. Currently, the most available tissue that reflects the immune system is peripheral blood mononuclear cells (PBMCs). Thus, the aim of this study was to identify key PBMC biomarkers of T1DM. Methods Common differentially expressed genes (DEGs) were screened from the Gene Expression Omnibus (GEO) datasets GSE9006, GSE72377, and GSE55098, and PBMC mRNA expression in T1DM patients was compared with that in healthy participants by GEO2R. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network analyses of DEGs were performed using the Cytoscape, DAVID, and STRING databases. The vital hub genes were validated by reverse transcription-polymerase chain reaction using clinical samples. The disease-gene-drug interaction network was built using the Comparative Toxicogenomics Database (CTD) and Drug Gene Interaction Database (DGIdb). Results We found that various biological functions or pathways related to the immune system and glucose metabolism changed in PBMCs from T1DM patients. In the PPI network, the DEGs of module 1 were significantly enriched in processes including inflammatory and immune responses and in pathways of proteoglycans in cancer. Moreover, we focused on four vital hub genes, namely, chitinase-3-like protein 1 (CHI3L1), C-X-C motif chemokine ligand 1 (CXCL1), matrix metallopeptidase 9 (MMP9), and granzyme B (GZMB), and confirmed them in clinical PBMC samples. Furthermore, the disease-gene-drug interaction network revealed the potential of key genes as reference markers in T1DM. Conclusion These results provide new insight into T1DM pathogenesis and novel biomarkers that could be widely representative reference indicators or potential therapeutic targets for clinical applications.

وصف الملف: electronic resource

العلاقة: http://e-dmj.org/upload/pdf/dmj-2021-0018.pdfTest; https://doaj.org/toc/2233-6079Test; https://doaj.org/toc/2233-6087Test

الوصول الحر: https://doaj.org/article/2b092515531e41838ebc4f9753f1caedTest

المؤلفون: Potts, Martin, Fletcher-Etherington, Alice, Nightingale, Katie, Mescia, Federica, Bergamaschi, Laura, Calero-Nieto, Fernando J, Antrobus, Robin, Williamson, James, Cambridge Institute Of Therapeutic Immunology And Infectious Disease-National Institute Of Health Research CITIID-NIHR COVID BioResource Collaboration, Parsons, Harriet, Huttlin, Edward L, Kingston, Nathalie, Göttgens, Berthold, Bradley, John R, Lehner, Paul J, Matheson, Nicholas J, Smith, Kenneth GC, Wills, Mark R, Lyons, Paul A, Weekes, Michael P

مصطلحات موضوعية: CP Immunology, Humans, COVID-19, SARS-CoV-2, Leukocytes, Mononuclear, Proteomics, Phenotype

الوصف: Certain serum proteins, including C-reactive protein (CRP) and D-dimer, have prognostic value in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nonetheless, these factors are non-specific, providing limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations that drive the pathogenesis of severe COVID-19. To identify cellular phenotypes associated with disease, we performed a comprehensive, unbiased analysis of total and plasma-membrane PBMC proteomes from 40 unvaccinated individuals with SARS-CoV-2, spanning the whole disease spectrum. Combined with RNA sequencing (RNA-seq) and flow cytometry from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing that immune-cell dysregulation progresses with increasing disease. The cell-surface proteins CEACAMs1, 6, and 8, CD177, CD63, and CD89 are strongly associated with severe COVID-19, corresponding to the emergence of atypical CD3+CD4+CEACAM1/6/8+CD177+CD63+CD89+ ...

العلاقة: https://dx.doi.org/10.1101/2022.11.16.22282338Test

الإتاحة: https://doi.org/10.17863/cam.9687810.1101/2022.11.16.22282338Test
https://www.repository.cam.ac.uk/handle/1810/350219Test

المؤلفون: Fu, Li-xin, Chen, Tao, Guo, Zai-Pei, Cao, Na, Zhang, Li-Wen, Zhou, Pei-Mei

المصدر: Anais Brasileiros de Dermatologia. August 2021 96(4)

مصطلحات موضوعية: Interleukins, Leukocytes, mononuclear, Psoriasis

الوصف: Background: Interferon (IFN)-λ1, also named Interleukin (IL)-29, is a new member of the Type III IFN or IFN-λ family. IL-29 plays an important role in the pathogenesis of many types of autoimmune and inflammatory diseases. Objective: To study the role of IL-29 in the pathogenesis of psoriasis vulgaris. Methods: The authors detected the serum levels of IL-29 in forty-one patients with psoriasis vulgaris, twenty-three patients with atopic dermatitis and thirty-eight age and gender-matched controls by sandwich Enzyme-Linked Immunosorbent Assay (ELISA). The effects of IL-29 on the expression of cytokines, such as IL-6, IL-17, IL-8, IL-4, IL10, Interferon (IFN-γ) and Tumor Necrosis Factor-α (TNF-α), in PBMCs and HaCat cells were determined by real-time quantitative PCR. Results: Our data indicated that serum IL-29 levels were significantly elevated in patients with psoriasis vulgaris when compared with atopic dermatitis patients and the control group. Moreover, Serum levels of IL-29 were closely associated with the severity of psoriasis vulgaris. Furthermore, IL-29 up-regulated the mRNA expression levels of IL-6, IL-17 and TNF-α in PBMCs from psoriasis vulgaris patients. In addition, IL-29 enhanced the IL-6 and IL-8 expression from the HaCat cells. Conclusion: This study provides the first observations on the association of IL-29 and psoriasis vulgaris and showed elevated IL-29 serum levels. The authors suggest that IL-29 may play a role in the pathogenesis of psoriasis vulgaris.

وصف الملف: text/html

الوصول الحر: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0365-05962021000400416Test

المؤلفون: Li-xin Fu, Tao Chen, Zai-Pei Guo, Na Cao, Li-Wen Zhang, Pei-Mei Zhou

المصدر: Anais Brasileiros de Dermatologia, Vol 96, Iss 4, Pp 416-421 (2021)

مصطلحات موضوعية: Interleukins, Leukocytes, mononuclear, Psoriasis, Dermatology, RL1-803

الوصف: Abstract Background: Interferon (IFN)-λ1, also named Interleukin (IL)-29, is a new member of the Type III IFN or IFN-λ family. IL-29 plays an important role in the pathogenesis of many types of autoimmune and inflammatory diseases. Objective: To study the role of IL-29 in the pathogenesis of psoriasis vulgaris. Methods: The authors detected the serum levels of IL-29 in forty-one patients with psoriasis vulgaris, twenty-three patients with atopic dermatitis and thirty-eight age and gender-matched controls by sandwich Enzyme-Linked Immunosorbent Assay (ELISA). The effects of IL-29 on the expression of cytokines, such as IL-6, IL-17, IL-8, IL-4, IL10, Interferon (IFN-γ) and Tumor Necrosis Factor-α (TNF-α), in PBMCs and HaCat cells were determined by real-time quantitative PCR. Results: Our data indicated that serum IL-29 levels were significantly elevated in patients with psoriasis vulgaris when compared with atopic dermatitis patients and the control group. Moreover, Serum levels of IL-29 were closely associated with the severity of psoriasis vulgaris. Furthermore, IL-29 up-regulated the mRNA expression levels of IL-6, IL-17 and TNF-α in PBMCs from psoriasis vulgaris patients. In addition, IL-29 enhanced the IL-6 and IL-8 expression from the HaCat cells. Conclusion: This study provides the first observations on the association of IL-29 and psoriasis vulgaris and showed elevated IL-29 serum levels. The authors suggest that IL-29 may play a role in the pathogenesis of psoriasis vulgaris.

وصف الملف: electronic resource

العلاقة: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0365-05962021000400416&tlng=enTest; https://doaj.org/toc/0365-0596Test

الوصول الحر: https://doaj.org/article/e5bd0341d7694be98a22a8e85e36c7d3Test

المؤلفون: Pedersen, Janni Maria, Hansen, Aida Solhøj, Skejø, Cæcilie, Juul-Madsen, Kristian, Junker, Peter, Hørslev-Petersen, Kim, Hetland, Merete Lund, Stengaard-Pedersen, Kristian, Østergaard, Mikkel, Møller, Bjarne Kuno, Dreyer, Lene, Hauge, Ellen-Margrethe, Hvid, Malene, Greisen, Stinne, Deleuran, Bent

المصدر: Pedersen, J M, Hansen, A S, Skejø, C, Juul-Madsen, K, Junker, P, Hørslev-Petersen, K, Hetland, M L, Stengaard-Pedersen, K, Østergaard, M, Møller, B K, Dreyer, L, Hauge, E M, Hvid, M, Greisen, S & Deleuran, B 2023, ' Lymphocyte activation gene 3 is increased and affects cytokine production in rheumatoid arthritis ', Arthritis Research and Therapy, vol. 25, no. 1, 97 . https://doi.org/10.1186/s13075-023-03073-zTest
Pedersen, J M, Hansen, A S, Skejø, C, Juul-Madsen, K, Junker, P, Hørslev-Petersen, K, Hetland, M L, Stengaard-Pedersen, K, Østergaard, M, Møller, B K, Dreyer, L, Hauge, E-M, Hvid, M, Greisen, S & Deleuran, B 2023, ' Lymphocyte activation gene 3 is increased and affects cytokine production in rheumatoid arthritis ', Arthritis Research & Therapy, vol. 25, no. 1, 97 . https://doi.org/10.1186/s13075-023-03073-zTest

مصطلحات موضوعية: Inflammation, Arthritis, Rheumatoid/metabolism, Leukocytes, Mononuclear/metabolism, LAG-3, Cytokines/metabolism, Humans, Galectin-3, Rheumatoid arthritis, Lymphocyte Activation, Synovial Fluid/metabolism, Co-inhibitory receptors, Autoantibodies

الوصف: BackgroundLymphocyte activation gene-3 (LAG-3) inhibits T cell activation and interferes with the immune response by binding to MHC-II. As antigen presentation is central in rheumatoid arthritis (RA) pathogenesis, we studied aspects of LAG-3 as a serological marker and mediator in the pathogenesis of RA. Since Galectin-3 (Gal-3) is described as an additional binding partner for LAG-3, we also aimed to study the functional importance of this interaction.MethodsPlasma levels of soluble (s) LAG-3 were measured in early RA patients (eRA, n = 99) at baseline and after 12 months on a treat-to-target protocol, in self-reportedly healthy controls (HC, n = 32), and in paired plasma and synovial fluid (SF) from chronic RA patients (cRA, n = 38). Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were examined for LAG-3 expression by flow cytometry. The binding and functional outcomes of LAG-3 and Gal-3 interaction were assessed with surface plasmon resonance (SPR) and in cell cultures using rh-LAG3, an antagonistic LAG-3 antibody and a Gal-3 inhibitor.ResultsBaseline sLAG-3 in the plasma was increased in eRA compared to HC and remained significantly elevated throughout 12 months of treatment. A high level of sLAG-3 at baseline was associated with the presence of IgM-RF and anti-CCP as well as radiographic progression. In cRA, sLAG-3 was significantly increased in SF compared with plasma, and LAG-3 was primarily expressed by activated T cells in SFMCs compared to PBMCs. Adding recombinant human LAG-3 to RA cell cultures resulted in decreased cytokine secretion, whereas blocking LAG-3 with an antagonistic antibody resulted in increased cytokine secretion. By SPR, we found a dose-dependent binding between LAG-3 and Gal-3. However, inhibiting Gal-3 in cultures did not further change cytokine production.ConclusionssLAG-3 in the plasma and synovial fluid is increased in both early and chronic RA patients, particularly in the inflamed joint. High levels of sLAG-3 are associated with autoantibody seropositivity and radiographic progression in eRA, and LAG-3 plays a biologically active role in cRA by decreasing inflammatory cytokine production. This functional outcome is not affected by Gal-3 interference. Our results suggest that LAG-3 is a faceted regulator of inflammation in early and chronic RA.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::33271edfee5f653ef0d5ee2daad97e49Test
https://pure.au.dk/portal/da/publications/lymphocyte-activation-gene-3-is-increased-and-affects-cytokine-production-in-rheumatoid-arthritisTest(c4cab09a-a3fc-44ba-8234-a4ecf3785a17).html

المؤلفون: Zhao, XF, Huffman, LD, Hafner, H, Athaiya, M, Finneran, MC, Kalinski, AL, Kohen, R, Flynn, C, Passino, R, Johnson, CN, Kohrman, D, Kawaguchi, R, Yang, LJS, Twiss, JL, Geschwind, DH, Corfas, G, Giger, RJ

مصطلحات موضوعية: Wallerian degeneration, immunology, inflammation, mouse, neuroscience, parabiosis, regeneration, sciatic nerve, single-cell RNA seq, Mice, Animals, Wallerian Degeneration, Leukocytes, Mononuclear, Sciatic Nerve, Nerve Degeneration, Nerve Crush, Peripheral Nerve Injuries, Nerve Regeneration, Cytoskeletal Proteins, Armadillo Domain Proteins

الوصف: Upon trauma, the adult murine peripheral nervous system (PNS) displays a remarkable degree of spontaneous anatomical and functional regeneration. To explore extrinsic mechanisms of neural repair, we carried out single-cell analysis of naïve mouse sciatic nerve, peripheral blood mono-nuclear cells, and crushed sciatic nerves at 1 day, 3 days, and 7 days following injury. During the first week, monocytes and macrophages (Mo/Mac) rapidly accumulate in the injured nerve and undergo extensive metabolic reprogramming. Proinflammatory Mo/Mac with a high glycolytic flux dominate the early injury response and rapidly give way to inflammation resolving Mac, programmed toward oxidative phosphorylation. Nerve crush injury causes partial leakiness of the blood–nerve barrier, proliferation of endoneurial and perineurial stromal cells, and entry of opsonizing serum proteins. Micro-dissection of the nerve injury site and distal nerve, followed by single-cell RNA-sequencing, identified distinct immune compartments, triggered ...

وصف الملف: Electronic

الإتاحة: https://doi.org/10.7302/22812Test
http://deepblue.lib.umich.edu/handle/2027.42/193167Test

المؤلفون: Guo, Shuang A, Bowyer, Georgina S, Ferdinand, John R, Maes, Mailis, Tuong, Zewen K, Gillman, Eleanor, Liao, Mingfeng, Lindeboom, Rik GH, Yoshida, Masahiro, Worlock, Kaylee, Gopee, Hudaa, Stephenson, Emily, Gao, Catherine A, Lyons, Paul A, Smith, Kenneth GC, Haniffa, Muzlifah, Meyer, Kerstin B, Nikolić, Marko Z, Zhang, Zheng, Wunderink, Richard G, Misharin, Alexander V, Dougan, Gordon, Navapurkar, Vilas, Teichmann, Sarah A, Conway Morris, Andrew, Clatworthy, Menna R

المساهمون: Guo, Shuang A [0000-0002-1712-9180], Bowyer, Georgina S [0000-0002-2058-4045], Ferdinand, John R [0000-0003-0936-0128], Maes, Mailis [0000-0002-0266-6557], Tuong, Zewen K [0000-0002-6735-6808], Gillman, Eleanor [0000-0002-4221-7270], Lindeboom, Rik GH [0000-0002-3660-504X], Yoshida, Masahiro [0000-0002-3521-5322], Worlock, Kaylee [0000-0002-5656-7634], Gopee, Hudaa [0000-0001-8507-5682], Stephenson, Emily [0000-0002-4244-4019], Gao, Catherine A [0000-0001-5576-3943], Lyons, Paul A [0000-0001-7035-8997], Smith, Kenneth GC [0000-0003-3829-4326], Haniffa, Muzlifah [0000-0002-3927-2084], Meyer, Kerstin B [0000-0001-5906-1498], Nikolić, Marko Z [0000-0001-6304-6848], Zhang, Zheng [0000-0002-3544-1389], Wunderink, Richard G [0000-0002-8527-4195], Misharin, Alexander V [0000-0003-2879-3789], Dougan, Gordon [0000-0003-0022-965X], Navapurkar, Vilas [0000-0002-3610-3568], Teichmann, Sarah A [0000-0002-6294-6366], Conway Morris, Andrew [0000-0002-3211-3216], Clatworthy, Menna R [0000-0002-3340-9828], Apollo - University of Cambridge Repository

المصدر: American Journal of Respiratory and Critical Care Medicine. 207:566-576

مصطلحات موضوعية: Adult, Pulmonary and Respiratory Medicine, obesity, Pediatric Obesity, SARS-CoV-2, COVID-19, Critical Care and Intensive Care Medicine, single-cell RNA sequencing, type-I interferon, Interferon Type I, Leukocytes, Mononuclear, bronchoalveolar lavage, Humans, Child, Lung

الوصف: Rationale: Obesity affects 40% of U.S. adults, is associated with a proinflammatory state, and presents a significant risk factor for the development of severe coronavirus disease (COVID-19). To date, there is limited information on how obesity might affect immune cell responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objectives: To determine the impact of obesity on respiratory tract immunity in COVID-19 across the human lifespan. Methods: We analyzed single-cell transcriptomes from BAL in three ventilated adult cohorts with (n = 24) or without (n = 9) COVID-19 from nasal immune cells in children with (n = 14) or without (n = 19) COVID-19, and from peripheral blood mononuclear cells in an independent adult COVID-19 cohort (n = 42), comparing obese and nonobese subjects. Measurements and Main Results: Surprisingly, we found that obese adult subjects had attenuated lung immune or inflammatory responses in SARS-CoV-2 infection, with decreased expression of IFN-α, IFN-γ, and TNF-α (tumor necrosis factor α) response gene signatures in almost all lung epithelial and immune cell subsets, and lower expression of IFNG and TNF in specific lung immune cells. Peripheral blood immune cells in an independent adult cohort showed a similar but less marked reduction in type-I IFN and IFNγ response genes, as well as decreased serum IFNα, in obese patients with SARS-CoV-2. Nasal immune cells from obese children with COVID-19 also showed reduced enrichment of IFN-α and IFN-γ response genes. Conclusions: These findings show blunted tissue immune responses in obese patients with COVID-19, with implications for treatment stratification, supporting the specific application of inhaled recombinant type-I IFNs in this vulnerable subset.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3e06241f4fda7bfb6aa0e6b3d8366813Test
https://doi.org/10.1164/rccm.202204-0751ocTest

المؤلفون: Jeffrey S. Weber, Benjamin A. Levinson, Andressa S. Laino, Anna C. Pavlick, David M. Woods

المصدر: Melanoma research. 32(5)

مصطلحات موضوعية: Histone Deacetylase Inhibitors, Cancer Research, Nivolumab, Pyrimidines, Skin Neoplasms, Oncology, Antineoplastic Combined Chemotherapy Protocols, Benzamides, Leukocytes, Mononuclear, Humans, Dermatology, Ipilimumab, Melanoma

الوصف: Checkpoint immunotherapies (CPIs) have improved outcomes for metastatic melanoma patients, with objective response rates to combination ipilimumab and nivolumab of ~58%. Preclinical data suggest that histone deacetylase (HDAC) inhibition enhances antitumor immune activity and may augment CPI. In a phase Ib open-label pilot trial (NCT03565406), patients with therapy-naive metastatic melanoma were treated with the class I/IV HDAC inhibitor mocetinostat orally three times a week in combination with nivolumab and ipilimumab every 3 weeks for 12 weeks followed by 12-week maintenance cycles of nivolumab every 2 weeks and mocetinostat at the same dose and schedule as induction. The endpoints of the trial were safety, definition of a recommended phase 2 dose, preliminary assessment of response, and correlative marker determination. Patient PBMC and serum samples collected at baseline and on-treatment were assessed by flow cytometry and Luminex assays for immune correlates. Ten patients were treated: nine with 70-mg and one with 50-mg mocetinostat. In the 70-mg cohort, eight patients had objective responses. The patient in the 50-mg cohort had an early progression of disease. All patients had grade 2 or higher toxicities, and six had grades 3 and 4 toxicities. Patient PBMC showed significant decreases in myeloid-derived suppressor cells and trends towards reduced anti-inflammatory monocyte phenotypes. Patient serum showed significant upregulation of granzyme A and TNF and trends towards increased granzyme B and IFNγ. Collectively, combining CPI and mocetinostat had favorable response rates but with high levels of toxicity. Assessment of immune correlates supports a shift away from immunosuppressive phenotypes towards enhanced immune responses.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e0e4deae7f2f0ab67051c77dc0003225Test
https://pubmed.ncbi.nlm.nih.gov/35678233Test

المؤلفون: Ashley Pitzer, Fernando Elijovich, Cheryl L. Laffer, Lale A. Ertuglu, Melis Sahinoz, Mohammad Saleem, Jaya Krishnan, Thanvi Dola, Luul A. Aden, Quanhu Sheng, Michael A. Raddatz, Celestine Wanjalla, Suman Pakala, Sean S. Davies, David M. Patrick, Valentina Kon, T. Alp Ikizler, Thomas Kleyman, Annet Kirabo

المصدر: Circulation research. 131(4)

مصطلحات موضوعية: Physiology, Inflammasomes, Interleukin-1beta, Sodium, Sodium Chloride, Mice, Inbred C57BL, Epitopes, Mice, Hypertension, NLR Family, Pyrin Domain-Containing 3 Protein, Leukocytes, Mononuclear, Animals, Humans, Sodium Chloride, Dietary, Cardiology and Cardiovascular Medicine, Epithelial Sodium Channels

الوصف: Background: Salt sensitivity of blood pressure is an independent predictor of cardiovascular morbidity and mortality. The exact mechanism by which salt intake increases blood pressure and cardiovascular risk is unknown. We previously found that sodium entry into antigen-presenting cells (APCs) via the amiloride-sensitive epithelial sodium channel EnaC (epithelial sodium channel) leads to the formation of IsoLGs (isolevuglandins) and release of proinflammatory cytokines to activate T cells and modulate salt-sensitive hypertension. In the current study, we hypothesized that ENaC-dependent entry of sodium into APCs activates the NLRP3 (NOD [nucleotide-binding and oligomerization domain]-like receptor family pyrin domain containing 3) inflammasome via IsoLG formation leading to salt-sensitive hypertension. Methods: We performed RNA sequencing on human monocytes treated with elevated sodium in vitro and Cellular Indexing of Transcriptomes and Epitopes by Sequencing analysis of peripheral blood mononuclear cells from participants rigorously phenotyped for salt sensitivity of blood pressure using an established inpatient protocol. To determine mechanisms, we analyzed inflammasome activation in mouse models of deoxycorticosterone acetate salt–induced hypertension as well as salt-sensitive mice with ENaC inhibition or expression, IsoLG scavenging, and adoptive transfer of wild-type dendritic cells into NLRP3 deficient mice. Results: We found that high levels of salt exposure upregulates the NLRP3 inflammasome, pyroptotic and apoptotic caspases, and IL (interleukin)-1β transcription in human monocytes. Cellular Indexing of Transcriptomes and Epitopes by Sequencing revealed that components of the NLRP3 inflammasome and activation marker IL-1β dynamically vary with changes in salt loading/depletion. Mechanistically, we found that sodium-induced activation of the NLRP3 inflammasome is ENaC and IsoLG dependent. NLRP3 deficient mice develop a blunted hypertensive response to elevated sodium, and this is restored by the adoptive transfer of NLRP3 replete APCs. Conclusions: These findings reveal a mechanistic link between ENaC, inflammation, and salt-sensitive hypertension involving NLRP3 inflammasome activation in APCs. APC activation via the NLRP3 inflammasome can serve as a potential diagnostic biomarker for salt sensitivity of blood pressure.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e33cd1d3b378c908e13bf48edcc00ad4Test
https://pubmed.ncbi.nlm.nih.gov/35862128Test

المؤلفون: Jenell S, Coleman, Clarissa P, Diniz, Edward J, Fuchs, Mark A, Marzinke, Wutyi, Aung, Rahul P, Bakshi, Homayoon, Farzadegan, Jay H, Bream, Tricia L, Nilles, Sherry, Hudson, Namandjé N, Bumpus, George J, Schwartz, Michael A, Rosenblum, James F, Rooney, Craig W, Hendrix

المصدر: JAIDS Journal of Acquired Immune Deficiency Syndromes. 92:89-96

مصطلحات موضوعية: Infectious Diseases, Leukocytes, Mononuclear, Humans, Emtricitabine, Female, HIV Infections, Pharmacology (medical), Medroxyprogesterone Acetate, Tenofovir

الوصف: Depot medroxyprogesterone acetate (DMPA) is a widely used contraceptive method. HIV pre-exposure prophylaxis with emtricitabine and tenofovir disoproxil fumarate (F/TDF) is highly effective in reducing HIV acquisition in women. We sought to determine the impact of DMPA on F/TDF pharmacokinetics and pharmacodynamics.Twelve healthy premenopausal cisgender women were enrolled and each completed 4 sequential conditions: (1) baseline, (2) steady-state F/TDF alone, (3) steady-state F/TDF + DMPA, and (4) DMPA alone. Assessments included clinical, pharmacokinetic, viral infectivity (ex vivo challenge of peripheral blood mononuclear cells by X4- and R5-tropic green fluorescent protein pseudoviruses and cervical tissue by HIV BaL ), endocrine, immune cell phenotyping, and renal function.Compared with baseline, F/TDF (± DMPA) significantly decreased both %R5- and X4-infected CD4 T cells and F/TDF + DMPA decreased cervical explant p24 (all P0.05). The %R5- and X4-infected CD4 T cells were higher during DMPA alone than during F/TDF periods and lower than baseline (not statistically significant). Cervical explant p24 fell between baseline and F/TDF values (not statistically significant). There were neither statistically significant differences in F/TDF pharmacokinetics, including total or renal clearance of either antiviral drug, nor changes in glomerular filtration rate with the addition of DMPA. There were few immune cell phenotypic differences across conditions.F/TDF decreased HIV infection in both challenge assays, whereas DMPA alone did not enhance HIV infection in either challenge assay. DMPA did not alter F/TDF pharmacokinetics or renal function.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b1ac9fd31d7476d7fe8b5e7491f48c3eTest
https://doi.org/10.1097/qai.0000000000003113Test