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Article ; Online: Stay in the Loop: New Insights about Randall's Plaques and Stone Disease.

Mitchell, Tanecia

American journal of physiology. Renal physiology

2018

Language	English
Publishing date	2018-09-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00409.2018
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Article ; Online: Bioenergetic profiles of peripheral mononuclear cells and systemic inflammation in women with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS).

Kumar, Parveen / Oster, Robert A / Assimos, Dean G / Ness, Timothy J / Mitchell, Tanecia

PloS one

2024 Volume 19, Issue 2, Page(s) e0298981

Abstract: Inflammation is thought to contribute to the etiology of interstitial cystitis/bladder pain syndrome (IC/BPS). It is well-known that disruption in metabolism in immune cells contributes to inflammation in several inflammatory diseases. The purpose of ... ...

Abstract	Inflammation is thought to contribute to the etiology of interstitial cystitis/bladder pain syndrome (IC/BPS). It is well-known that disruption in metabolism in immune cells contributes to inflammation in several inflammatory diseases. The purpose of this study was to investigate whether cellular bioenergetics is altered in monocytes and lymphocytes from women with IC/BPS, and if these alterations correlate with systemic inflammatory markers. Age and BMI matched adult healthy women (HS; n = 18) and women with IC/BPS (n = 18) were included in the study. Blood was collected to assess cellular bioenergetics in monocytes and lymphocytes using a Seahorse XF96 Analyzer and plasma cytokine levels were measured using Meso Scale Discovery immunoassays. The correlation between bioenergetic parameters, cytokines, and demographics was determined using Pearson correlation coefficients. Means of the two groups were compared using the two-group t-test. Patients with IC/BPS had reduced monocyte oxygen consumption rates and glycolytic rates compared to healthy subjects. In contrast, lymphocytes from these patients had increased oxygen consumption rates and glycolytic rates. Several cytokines and chemokines including Interferon-gamma (IFN-ɣ), tumor necrosis factor alpha (TNF-ɑ), Interleukin-6 (IL-6), Interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) levels were significantly elevated in the plasma of patients with IC/BPS. However, Transforming growth factor (TGF-β) and Interleukin-10 (IL-10) levels were significantly decreased in IC/BPS patients compared to HS. In addition, Interferon gamma (IFN-ɣ), TNF-ɑ, IL-8, and TGF-β levels correlated with several bioenergetic parameters in monocytes or lymphocytes from healthy subjects. In contrast, TNF-ɑ and IL-8 correlated with bioenergetic parameters in monocytes from IC/BPS patients. Monocyte and lymphocyte cellular bioenergetics and plasma cytokine levels are different in patients with IC/PBS compared to HS. It appears that systemic inflammation is greater in this cohort which may negatively impact immune cell function. The relationship between cellular bioenergetics and inflammation in monocytes and lymphocytes could be important in understanding the pathogenesis of IC/PBS and warrants further investigation.
MeSH term(s)	Adult ; Humans ; Female ; Cystitis, Interstitial/metabolism ; Interleukin-8/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Inflammation/metabolism ; Cytokines/metabolism ; Energy Metabolism ; Transforming Growth Factor beta/metabolism
Chemical Substances	Interleukin-8 ; Tumor Necrosis Factor-alpha ; Vascular Endothelial Growth Factor A ; Cytokines ; Transforming Growth Factor beta
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0298981
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Article ; Online: Novel Translational Approaches To Study Kidney Disease.

Laurence, Emma / Kumar, Parveen / Mitchell, Tanecia

Journal of visualized experiments : JoVE

2022 , Issue 186

MeSH term(s)	Humans ; Kidney Diseases ; Translational Research, Biomedical
Language	English
Publishing date	2022-08-30
Publishing country	United States
Document type	Editorial ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/64711
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Article ; Online: Oxalate disrupts monocyte and macrophage cellular function via Interleukin-10 and mitochondrial reactive oxygen species (ROS) signaling.

Kumar, Parveen / Laurence, Emma / Crossman, David K / Assimos, Dean G / Murphy, Michael P / Mitchell, Tanecia

Redox biology

2023 Volume 67, Page(s) 102919

Abstract: Oxalate is a small compound found in certain plant-derived foods and is a major component of calcium oxalate (CaOx) kidney stones. Individuals that consume oxalate enriched meals have an increased risk of forming urinary crystals, which are precursors to ...

Abstract	Oxalate is a small compound found in certain plant-derived foods and is a major component of calcium oxalate (CaOx) kidney stones. Individuals that consume oxalate enriched meals have an increased risk of forming urinary crystals, which are precursors to CaOx kidney stones. We previously reported that a single dietary oxalate load induces nanocrystalluria and reduces monocyte cellular bioenergetics in healthy adults. The purpose of this study was to extend these investigations to identify specific oxalate-mediated mechanisms in monocytes and macrophages. We performed RNA-Sequencing analysis on monocytes isolated from healthy subjects exposed to a high oxalate (8 mmol) dietary load. RNA-sequencing revealed 1,198 genes were altered and Ingenuity Pathway Analysis demonstrated modifications in several pathways including Interleukin-10 (IL-10) anti-inflammatory cytokine signaling, mitochondrial metabolism and function, oxalic acid downstream signaling, and autophagy. Based on these findings, we hypothesized that oxalate induces mitochondrial and lysosomal dysfunction in monocytes and macrophages via IL-10 and reactive oxygen species (ROS) signaling which can be reversed with exogenous IL-10 or Mitoquinone (MitoQ; a mitochondrial targeted antioxidant). We exposed monocytes and macrophages to oxalate in an in-vitro setting which caused oxidative stress, a decline in IL-10 cytokine levels, mitochondrial and lysosomal dysfunction, and impaired autophagy in both cell types. Administration of exogenous IL-10 and MitoQ attenuated these responses. These findings suggest that oxalate impairs metabolism and immune response via IL-10 signaling and mitochondrial ROS generation in both monocytes and macrophages which can be potentially limited or reversed. Future studies will examine the benefits of these therapies on CaOx crystal formation and growth in vivo.
MeSH term(s)	Adult ; Humans ; Monocytes/metabolism ; Oxalates ; Reactive Oxygen Species/metabolism ; Interleukin-10/metabolism ; Calcium Oxalate/metabolism ; Macrophages/metabolism ; Cytokines/metabolism ; Kidney Calculi/etiology ; Kidney Calculi/metabolism ; RNA
Chemical Substances	Oxalates ; Reactive Oxygen Species ; Interleukin-10 (130068-27-8) ; Calcium Oxalate (2612HC57YE) ; Cytokines ; RNA (63231-63-0)
Language	English
Publishing date	2023-10-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2023.102919
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Article ; Online: Estimation of Urinary Nanocrystals in Humans using Calcium Fluorophore Labeling and Nanoparticle Tracking Analysis.

Kumar, Parveen / Bell, Andrew / Mitchell, Tanecia

Journal of visualized experiments : JoVE

2021 , Issue 168

Abstract: Kidney stones are becoming more prevalent worldwide in adults and children. The most common type of kidney stone is comprised of calcium oxalate (CaOx) crystals. Crystalluria occurs when urine becomes supersaturated with minerals (e.g., calcium, oxalate, ...

Abstract	Kidney stones are becoming more prevalent worldwide in adults and children. The most common type of kidney stone is comprised of calcium oxalate (CaOx) crystals. Crystalluria occurs when urine becomes supersaturated with minerals (e.g., calcium, oxalate, phosphate) and precedes kidney stone formation. Standard methods to assess crystalluria in stone formers include microscopy, filtration, and centrifugation. However, these methods primarily detect microcrystals and not nanocrystals. Nanocrystals have been suggested to be more harmful to kidney epithelial cells than microcrystals in vitro. Here, we describe the ability of Nanoparticle Tracking analysis (NTA) to detect human urinary nanocrystals. Healthy adults were fed a controlled oxalate diet prior to drinking an oxalate load to stimulate urinary nanocrystals. Urine was collected for 24 hours before and after the oxalate load. Samples were processed and washed with ethanol to purify samples. Urinary nanocrystals were stained with the calcium binding fluorophore, Fluo-4 AM. After staining, the size and count of nanocrystals were determined using NTA. The findings from this study show NTA can efficiently detect nanocrystalluria in healthy adults. These findings suggest NTA could be a valuable early detection method of nanocrystalluria in patients with kidney stone disease.
MeSH term(s)	Adult ; Aniline Compounds/chemistry ; Calcium Oxalate/urine ; Gold/chemistry ; Humans ; Metal Nanoparticles/chemistry ; Nanoparticles/chemistry ; Xanthenes/chemistry
Chemical Substances	Aniline Compounds ; Fluo-5F-AM ; Xanthenes ; Calcium Oxalate (2612HC57YE) ; Gold (7440-57-5)
Language	English
Publishing date	2021-02-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/62192
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Article ; Online: Oxalate Alters Cellular Bioenergetics, Redox Homeostasis, Antibacterial Response, and Immune Response in Macrophages.

Kumar, Parveen / Saini, Kanchan / Saini, Vikram / Mitchell, Tanecia

Frontiers in immunology

2021 Volume 12, Page(s) 694865

Abstract: Individuals with calcium oxalate (CaOx) kidney stones can have secondarily infected calculi which may play a role in the development of recurrent urinary tract infection (UTI). ... ...

Abstract	Individuals with calcium oxalate (CaOx) kidney stones can have secondarily infected calculi which may play a role in the development of recurrent urinary tract infection (UTI). Uropathogenic
MeSH term(s)	Adenosine Triphosphate/biosynthesis ; Animals ; Bacterial Infections/immunology ; Cytokines/biosynthesis ; Energy Metabolism/drug effects ; Homeostasis/drug effects ; Humans ; Macrophages/drug effects ; Macrophages/immunology ; Macrophages/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Oxalates/pharmacology ; Oxidation-Reduction ; THP-1 Cells
Chemical Substances	Cytokines ; Oxalates ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2021-10-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.694865
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Article: Estimation of urinary nanocrystals in humans using calcium fluorophore labeling and nanoparticle tracking analysis

Kumar, Parveen / Bell, Andrew / Mitchell, Tanecia

Journal of visualized experiments. 2021 Feb. 09, , no. 168

2021

Abstract	Kidney stones are becoming more prevalent worldwide in adults and children. The most common type of kidney stone is comprised of calcium oxalate (CaOx) crystals. Crystalluria occurs when urine becomes supersaturated with minerals (e.g., calcium, oxalate, phosphate) and precedes kidney stone formation. Standard methods to assess crystalluria in stone formers include microscopy, filtration, and centrifugation. However, these methods primarily detect microcrystals and not nanocrystals. Nanocrystals have been suggested to be more harmful to kidney epithelial cells than microcrystals in vitro. Here, we describe the ability of Nanoparticle Tracking analysis (NTA) to detect human urinary nanocrystals. Healthy adults were fed a controlled oxalate diet prior to drinking an oxalate load to stimulate urinary nanocrystals. Urine was collected for 24 hours before and after the oxalate load. Samples were processed and washed with ethanol to purify samples. Urinary nanocrystals were stained with the calcium binding fluorophore, Fluo-4 AM. After staining, the size and count of nanocrystals were determined using NTA. The findings from this study show NTA can efficiently detect nanocrystalluria in healthy adults. These findings suggest NTA could be a valuable early detection method of nanocrystalluria in patients with kidney stone disease.
Keywords	calcium ; calcium oxalate ; centrifugation ; diet ; epithelium ; ethanol ; filtration ; fluorescent dyes ; humans ; kidneys ; microscopy ; nanocrystals ; phosphates ; renal calculi ; urine
Language	English
Dates of publication	2021-0209
Size	p. e62192.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/62192
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Sex differences in redox homeostasis in renal disease.

Mitchell, Tanecia / De Miguel, Carmen / Gohar, Eman Y

Redox biology

2020 Volume 31, Page(s) 101489

Abstract: Sex differences in redox signaling in the kidney present new challenges and opportunities for understanding the physiology and pathophysiology of the kidney. This review will focus on reactive oxygen species, immune-related signaling pathways and ... ...

Abstract	Sex differences in redox signaling in the kidney present new challenges and opportunities for understanding the physiology and pathophysiology of the kidney. This review will focus on reactive oxygen species, immune-related signaling pathways and endothelin-1 as potential mediators of sex-differences in redox homeostasis in the kidney. Additionally, this review will highlight male-female differences in redox signaling in several major cardiovascular and renal disorders namely acute kidney injury, diabetic nephropathy, kidney stone disease and salt-sensitive hypertension. Furthermore, we will discuss the contribution of redox signaling in the pathogenesis of postmenopausal hypertension and preeclampsia.
MeSH term(s)	Female ; Homeostasis ; Humans ; Kidney/metabolism ; Male ; Oxidation-Reduction ; Pregnancy ; Reactive Oxygen Species/metabolism ; Sex Characteristics
Chemical Substances	Reactive Oxygen Species
Language	English
Publishing date	2020-03-09
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2020.101489
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Article ; Online: Dietary Oxalate Induces Urinary Nanocrystals in Humans.

Kumar, Parveen / Patel, Mikita / Thomas, Vinoy / Knight, John / Holmes, Ross P / Mitchell, Tanecia

Kidney international reports

2020 Volume 5, Issue 7, Page(s) 1040–1051

Abstract: Introduction: Crystalluria is thought to be associated with kidney stone formation and can occur when urine becomes supersaturated with calcium, oxalate, and phosphate. The principal method used to identify urinary crystals is microscopy, with or ... ...

Abstract	Introduction: Crystalluria is thought to be associated with kidney stone formation and can occur when urine becomes supersaturated with calcium, oxalate, and phosphate. The principal method used to identify urinary crystals is microscopy, with or without a polarized light source. This method can detect crystals above 1 μm in diameter (microcrystals). However, analyses of calcium oxalate kidney stones have indicated that crystallite components in these calculi are 50-100 nm in diameter. Recent studies have suggested that nanocrystals (<200 nm) elicit more injury to renal cells compared to microcrystals. The purpose of this study was to determine whether (i) urinary nanocrystals can be detected and quantified by nanoparticle tracking analysis (NTA, a high-resolution imaging technology), (ii) early-void urine samples from healthy subjects contain calcium nanocrystals, and (iii) a dietary oxalate load increases urinary nanocrystal formation. Methods: Healthy subjects consumed a controlled low-oxalate diet for 3 days before a dietary oxalate load. Urinary crystals were isolated by centrifugation and assessed using NTA before and 5 hours after the oxalate load. The morphology and chemical composition of crystals was assessed using electron microscopy, Fourier-transform infrared spectroscopy (FTIR), and ion chromatography-mass spectrometry (IC-MS). Results: Urinary calcium oxalate nanocrystals were detected in pre-load samples and increased substantially following the oxalate load. Conclusion: These findings indicate that NTA can quantify urinary nanocrystals and that meals rich in oxalate can promote nanocrystalluria. NTA should provide valuable insight about the role of nanocrystals in kidney stone formation.
Language	English
Publishing date	2020-05-07
Publishing country	United States
Document type	Journal Article
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2020.04.029
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Article ; Online: Dietary Oxalate Loading Impacts Monocyte Metabolism and Inflammatory Signaling in Humans.

Kumar, Parveen / Patel, Mikita / Oster, Robert A / Yarlagadda, Vidhush / Ambrosetti, Adam / Assimos, Dean G / Mitchell, Tanecia

Frontiers in immunology

2021 Volume 12, Page(s) 617508

Abstract: Diet has been associated with several metabolic diseases and may impact immunity. Increased consumption of meals with high oxalate content may stimulate urinary calcium oxalate (CaOx) crystals, which are precursors to CaOx kidney stones. We previously ... ...

Abstract	Diet has been associated with several metabolic diseases and may impact immunity. Increased consumption of meals with high oxalate content may stimulate urinary calcium oxalate (CaOx) crystals, which are precursors to CaOx kidney stones. We previously reported that CaOx stone formers have decreased monocyte cellular bioenergetics compared to healthy participants and oxalate reduces monocyte metabolism and redox status Clinical trial registration: ClinicalTrials.gov, identifier NCT03877276.
MeSH term(s)	Adult ; Biomarkers ; Dietary Supplements ; Electron Transport Chain Complex Proteins/metabolism ; Energy Metabolism/drug effects ; Female ; Humans ; Inflammation/etiology ; Inflammation/metabolism ; Inflammation/pathology ; Leukocyte Count ; Male ; Mitochondria/drug effects ; Mitochondria/metabolism ; Monocytes/drug effects ; Monocytes/metabolism ; Oxalates/administration & dosage ; Signal Transduction/drug effects ; Urinalysis
Chemical Substances	Biomarkers ; Electron Transport Chain Complex Proteins ; Oxalates
Language	English
Publishing date	2021-02-25
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.617508
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