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Article ; Online: Reply.

Yalavarthi, Srilakshmi / Knight, Jason S

Arthritis & rheumatology (Hoboken, N.J.)

2016 Volume 68, Issue 5, Page(s) 1321–1322

Language	English
Publishing date	2016
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.39579
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Article ; Online: Visualization of Nuclease- and Serum-Mediated Chromatin Degradation with DNA-Histone Mesostructures.

Wasielewski, Midori L / Nguyen, Katherine / Yalavarthi, Srilakshmi / Ekbote, Pallavi / Weerappuli, Priyan D / Knight, Jason S / Takayama, Shuichi

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: This study analyzed the nuclease- and serum-driven degradation of millimeter-scale, circular DNA-histone mesostructures (DHMs). DHMs are bioengineered chromatin meshes of defined DNA and histone compositions designed as minimal mimetics of physiological ... ...

Abstract	This study analyzed the nuclease- and serum-driven degradation of millimeter-scale, circular DNA-histone mesostructures (DHMs). DHMs are bioengineered chromatin meshes of defined DNA and histone compositions designed as minimal mimetics of physiological extracellular chromatin structures, such as neutrophil extracellular traps (NETs). Taking advantage of the defined circular shape of the DHMs, an automated time-lapse imaging and image analysis method was developed and used to track DHM degradation and shape changes over time. DHMs were degraded well by 10 U/mL concentrations of deoxyribonuclease I (DNase I) but not by the same level of micrococcal nuclease (MNase), whereas NETs were degraded well by both nucleases. These comparative observations suggest that DHMs have a less accessible chromatin structure compared to NETs. DHMs were degraded by normal human serum, although at a slower rate than NETs. Interestingly, time-lapse images of DHMs revealed qualitative differences in the serum-mediated degradation process compared to that mediated by DNase I. Importantly, despite their reduced susceptibility to degradation and compositional simplicity, the DHMs mimicked NETs in being degraded to a greater extent by normal donor serum compared to serum from a lupus patient with high disease activity. These methods and insights are envisioned to guide the future development and expanded use of DHMs, beyond the previously reported antibacterial and immunostimulatory analyses, to extracellular chromatin-related pathophysiological and diagnostic studies.
MeSH term(s)	Humans ; Chromatin/metabolism ; Histones/metabolism ; Neutrophils/metabolism ; Extracellular Traps/metabolism ; DNA/metabolism ; Deoxyribonuclease I/metabolism
Chemical Substances	Chromatin ; Histones ; DNA (9007-49-2) ; Deoxyribonuclease I (EC 3.1.21.1)
Language	English
Publishing date	2023-02-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24043222
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Article ; Online: Low ectonucleotidase activity and increased neutrophil-platelet aggregates in patients with antiphospholipid syndrome.

NaveenKumar, Somanathapura K / Tambralli, Ajay / Fonseca, Bruna Mazetto / Yalavarthi, Srilakshmi / Liang, Wenying / Hoy, Claire K / Sarosh, Cyrus / Rysenga, Christine E / Ranger, Caroline H / Vance, Caroline E / Madison, Jacqueline A / Orsi, Fernanda A / Sood, Suman L / Schaefer, Jordan K / Zuo, Yu / Knight, Jason S

Blood

2024 Volume 143, Issue 12, Page(s) 1193–1197

Abstract: Abstract: Many patients with antiphospholipid syndrome had decreased ectonucleotidase activity on neutrophils and platelets, which enabled extracellular nucleotides to trigger neutrophil-platelet aggregates. This phenotype was replicated by treating ... ...

Abstract	Abstract: Many patients with antiphospholipid syndrome had decreased ectonucleotidase activity on neutrophils and platelets, which enabled extracellular nucleotides to trigger neutrophil-platelet aggregates. This phenotype was replicated by treating healthy neutrophils and platelets with patient-derived antiphospholipid antibodies or ectonucleotidase inhibitors.
MeSH term(s)	Humans ; Antiphospholipid Syndrome ; Neutrophils ; Antibodies, Antiphospholipid ; Blood Platelets
Chemical Substances	Antibodies, Antiphospholipid
Language	English
Publishing date	2024-01-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2023022097
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Article ; Online: Interaction of the antiphospholipid syndrome autoantigen beta-2 glycoprotein I with DNA and neutrophil extracellular traps.

Kmeťová, Katarína / Lonina, Elena / Yalavarthi, Srilakshmi / Levine, Jerrold S / Hoy, Claire K / Sarosh, Cyrus / Gockman, Kelsey / Morris, Alexandra E / Tambralli, Ajay / Madison, Jacqueline A / Zuo, Yu / Subang, Rebecca / Rauch, Joyce / Knight, Jason S

Clinical immunology (Orlando, Fla.)

2023 Volume 255, Page(s) 109714

Abstract: Beta-2 glycoprotein I ( ... ...

Abstract	Beta-2 glycoprotein I (β
Language	English
Publishing date	2023-07-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	1459903-x
ISSN	1521-7035 ; 1521-6616
ISSN (online)	1521-7035
ISSN	1521-6616
DOI	10.1016/j.clim.2023.109714
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Article ; Online: Inhibition of neutrophil extracellular trap formation alleviates vascular dysfunction in type 1 diabetic mice.

Liu, Chao / Yalavarthi, Srilakshmi / Tambralli, Ajay / Zeng, Lixia / Rysenga, Christine E / Alizadeh, Nikoo / Hudgins, Lucas / Liang, Wenying / NaveenKumar, Somanathapura K / Shi, Hui / Shelef, Miriam A / Atkins, Kevin B / Pennathur, Subramaniam / Knight, Jason S

Science advances

2023 Volume 9, Issue 43, Page(s) eadj1019

Abstract: While neutrophil extracellular traps (NETs) have previously been linked to some diabetes-associated complications, such as dysfunctional wound healing, their potential role in diabetic vascular dysfunction has not been studied. Diabetic Akita mice were ... ...

Abstract	While neutrophil extracellular traps (NETs) have previously been linked to some diabetes-associated complications, such as dysfunctional wound healing, their potential role in diabetic vascular dysfunction has not been studied. Diabetic Akita mice were crossed with either
MeSH term(s)	Mice ; Animals ; Extracellular Traps/metabolism ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 1/complications ; Diabetes Mellitus, Type 1/metabolism ; Acetylcholine ; Neutrophils/metabolism ; Thromboxanes/metabolism
Chemical Substances	Acetylcholine (N9YNS0M02X) ; Thromboxanes
Language	English
Publishing date	2023-10-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.adj1019
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Article ; Online: Non-criteria antiphospholipid antibodies and calprotectin as potential biomarkers in pediatric antiphospholipid syndrome.

Sloan, Elizabeth E / Kmetova, Katarina / NaveenKumar, Somanathapura K / Kluge, Lyndsay / Chong, Emily / Hoy, Claire K / Yalavarthi, Srilakshmi / Sarosh, Cyrus / Baisch, Jeanine / Walters, Lynnette / Nassi, Lorien / Fuller, Julie / Turnier, Jessica L / Pascual, Virginia / Wright, Tracey B / Madison, Jacqueline A / Knight, Jason S / Zia, Ayesha / Zuo, Yu

Clinical immunology (Orlando, Fla.)

2024 Volume 261, Page(s) 109926

Abstract: Our study aimed to evaluate the presence, clinical associations, and potential mechanistic roles of non-criteria antiphospholipid antibodies (aPL) and circulating calprotectin, a highly stable marker of neutrophil extracellular trap release (NETosis), in ...

Abstract	Our study aimed to evaluate the presence, clinical associations, and potential mechanistic roles of non-criteria antiphospholipid antibodies (aPL) and circulating calprotectin, a highly stable marker of neutrophil extracellular trap release (NETosis), in pediatric APS patients. We found that 79% of pediatric APS patients had at least one non-criteria aPL at moderate-to-high titer. Univariate logistic regression demonstrated that positive anti-beta-2 glycoprotein I domain 1 (anti-D1) IgG (p = 0.008), anti-phosphatidylserine/prothrombin (aPS/PT) IgG (p < 0.001), and aPS/PT IgM (p < 0.001) were significantly associated with venous thrombosis. Positive anti-D1 IgG (p < 0.001), aPS/PT IgG (p < 0.001), and aPS/PT IgM (p = 0.001) were also associated with non-thrombotic manifestations of APS, such as thrombocytopenia. Increased levels of calprotectin were detected in children with APS. Calprotectin correlated positively with absolute neutrophil count (r = 0.63, p = 0.008) and negatively with platelet count (r = -0.59, p = 0.015). Mechanistically, plasma from pediatric APS patients with high calprotectin levels impaired platelet viability in a dose-dependent manner.
MeSH term(s)	Humans ; Child ; Antibodies, Antiphospholipid ; Antiphospholipid Syndrome ; Biomarkers ; beta 2-Glycoprotein I ; Immunoglobulin G ; Immunoglobulin M ; Prothrombin ; Leukocyte L1 Antigen Complex
Chemical Substances	Antibodies, Antiphospholipid ; Biomarkers ; beta 2-Glycoprotein I ; Immunoglobulin G ; Immunoglobulin M ; Prothrombin (9001-26-7) ; Leukocyte L1 Antigen Complex
Language	English
Publishing date	2024-02-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1459903-x
ISSN	1521-7035 ; 1521-6616
ISSN (online)	1521-7035
ISSN	1521-6616
DOI	10.1016/j.clim.2024.109926
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Article: Autoantibodies stabilize neutrophil extracellular traps in COVID-19.

Zuo, Yu / Yalavarthi, Srilakshmi / Navaz, Sherwin / Hoy, Claire / Harbaugh, Alyssa / Gockman, Kelsey / Zuo, Melanie / Madison, Jacqueline A / Shi, Hui / Kanthi, Yogendra / Knight, Jason S

medRxiv : the preprint server for health sciences

2021

Abstract: The release of neutrophil extracellular traps ( ...

Abstract	The release of neutrophil extracellular traps (
Language	English
Publishing date	2021-06-24
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.03.31.21254692
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Article ; Online: Response to: 'Monocyte type I interferon signature in antiphospholipid syndrome is related to pro-inflammatory monocyte subsets, hydroxychloroquine and statin use' by van den Hoogen et al.

Yalavarthi, Srilakshmi / Grenn, Robert C / Knight, Jason S

Annals of the rheumatic diseases

2016 Volume 75, Issue 12, Page(s) e82

MeSH term(s)	Antibodies, Antiphospholipid ; Antiphospholipid Syndrome ; Humans ; Hydroxychloroquine ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Interferon Type I ; Monocytes
Chemical Substances	Antibodies, Antiphospholipid ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Interferon Type I ; Hydroxychloroquine (4QWG6N8QKH)
Language	English
Publishing date	2016
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	7090-7
ISSN	1468-2060 ; 0003-4967
ISSN (online)	1468-2060
ISSN	0003-4967
DOI	10.1136/annrheumdis-2016-210529
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Zs.MO 167: Show issues

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Article ; Online: SARS-CoV-2 Spike Protein S1-Mediated Endothelial Injury and Pro-Inflammatory State Is Amplified by Dihydrotestosterone and Prevented by Mineralocorticoid Antagonism.

Kumar, Nitin / Zuo, Yu / Yalavarthi, Srilakshmi / Hunker, Kristina L / Knight, Jason S / Kanthi, Yogendra / Obi, Andrea T / Ganesh, Santhi K

Viruses

2021 Volume 13, Issue 11

Abstract: Men are disproportionately affected by the coronavirus disease-2019 (COVID-19), and face higher odds of severe illness and death compared to women. The vascular effects of androgen signaling and inflammatory cytokines in severe acute respiratory syndrome ...

Abstract	Men are disproportionately affected by the coronavirus disease-2019 (COVID-19), and face higher odds of severe illness and death compared to women. The vascular effects of androgen signaling and inflammatory cytokines in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-mediated endothelial injury are not defined. We determined the effects of SARS-CoV-2 spike protein-mediated endothelial injury under conditions of exposure to androgen dihydrotestosterone (DHT) and tumor necrosis factor-a (TNF-α) and tested potentially therapeutic effects of mineralocorticoid receptor antagonism by spironolactone. Circulating endothelial injury markers VCAM-1 and E-selectin were measured in men and women diagnosed with COVID-19. Exposure of endothelial cells (ECs) in vitro to DHT exacerbated spike protein S1-mediated endothelial injury transcripts for the cell adhesion molecules E-selectin, VCAM-1 and ICAM-1 and anti-fibrinolytic PAI-1 (
MeSH term(s)	Angiotensin Receptor Antagonists/pharmacology ; COVID-19/pathology ; COVID-19/physiopathology ; COVID-19/virology ; Cell Adhesion Molecules/blood ; Cells, Cultured ; Dihydrotestosterone/pharmacology ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/pathology ; Female ; Humans ; Inflammation ; Male ; SARS-CoV-2/physiology ; Sex Characteristics ; Spike Glycoprotein, Coronavirus/physiology ; Spironolactone/pharmacology ; Tumor Necrosis Factor-alpha/pharmacology ; Tumor Necrosis Factor-alpha/physiology ; Valsartan/pharmacology
Chemical Substances	Angiotensin Receptor Antagonists ; Cell Adhesion Molecules ; Spike Glycoprotein, Coronavirus ; Tumor Necrosis Factor-alpha ; spike protein, SARS-CoV-2 ; Dihydrotestosterone (08J2K08A3Y) ; Spironolactone (27O7W4T232) ; Valsartan (80M03YXJ7I)
Language	English
Publishing date	2021-11-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13112209
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Article ; Online: Antineutrophil properties of natural gingerols in models of lupus.

Ali, Ramadan A / Gandhi, Alex A / Dai, Lipeng / Weiner, Julia / Estes, Shanea K / Yalavarthi, Srilakshmi / Gockman, Kelsey / Sun, Duxin / Knight, Jason S

JCI insight

2021 Volume 6, Issue 3

Abstract: Ginger is known to have antiinflammatory and antioxidative effects and has traditionally been used as an herbal supplement in the treatment of various chronic diseases. Here, we report antineutrophil properties of 6-gingerol, the most abundant bioactive ... ...

Abstract	Ginger is known to have antiinflammatory and antioxidative effects and has traditionally been used as an herbal supplement in the treatment of various chronic diseases. Here, we report antineutrophil properties of 6-gingerol, the most abundant bioactive compound of ginger root, in models of lupus and antiphospholipid syndrome (APS). Specifically, we demonstrate that 6-gingerol attenuates neutrophil extracellular trap (NET) release in response to lupus- and APS-relevant stimuli through a mechanism that is at least partially dependent on inhibition of phosphodiesterases. At the same time, administration of 6-gingerol to mice reduces NET release in various models of lupus and APS, while also improving other disease-relevant endpoints, such as autoantibody formation and large-vein thrombosis. In summary, this study is the first to our knowledge to demonstrate a protective role for ginger-derived compounds in the context of lupus. Importantly, it provides a potential mechanism for these effects via phosphodiesterase inhibition and attenuation of neutrophil hyperactivity.
MeSH term(s)	Animals ; Antibodies, Antiphospholipid/biosynthesis ; Antiphospholipid Syndrome/drug therapy ; Antiphospholipid Syndrome/immunology ; Antiphospholipid Syndrome/metabolism ; Catechols/blood ; Catechols/pharmacokinetics ; Catechols/pharmacology ; Disease Models, Animal ; Extracellular Traps/drug effects ; Extracellular Traps/immunology ; Fatty Alcohols/blood ; Fatty Alcohols/pharmacokinetics ; Fatty Alcohols/pharmacology ; Female ; Humans ; In Vitro Techniques ; Lupus Erythematosus, Systemic/drug therapy ; Lupus Erythematosus, Systemic/immunology ; Lupus Erythematosus, Systemic/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neutrophils/drug effects ; Neutrophils/immunology ; Neutrophils/metabolism ; Phosphodiesterase 4 Inhibitors/pharmacology ; Phosphodiesterase Inhibitors/blood ; Phosphodiesterase Inhibitors/pharmacokinetics ; Phosphodiesterase Inhibitors/pharmacology ; Phytotherapy ; Reactive Oxygen Species/metabolism ; Venous Thrombosis/drug therapy ; Venous Thrombosis/pathology
Chemical Substances	Antibodies, Antiphospholipid ; Catechols ; Fatty Alcohols ; Phosphodiesterase 4 Inhibitors ; Phosphodiesterase Inhibitors ; Reactive Oxygen Species ; gingerol (925QK2Z900)
Language	English
Publishing date	2021-02-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.138385
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