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Article ; Online: Matrix metalloproteinase-9 regulates afferent arteriolar remodeling and function in hypertension-induced kidney disease.

Feng, Wenguang / Guan, Zhengrong / Ying, Wei-Zhong / Xing, Dongqi / Ying, Kai Er / Sanders, Paul W

2023 Volume 104, Issue 4, Page(s) 740–753

Abstract: This study tested if matrix metalloproteinase (MMP)-9 promoted microvascular pathology that initiates hypertensive (HT) kidney disease in salt-sensitive (SS) Dahl rats. SS rats lacking Mmp9 ( ... ...

Abstract	This study tested if matrix metalloproteinase (MMP)-9 promoted microvascular pathology that initiates hypertensive (HT) kidney disease in salt-sensitive (SS) Dahl rats. SS rats lacking Mmp9 (Mmp9
MeSH term(s)	Rats ; Animals ; Matrix Metalloproteinase 9/genetics ; Sodium Chloride ; Rats, Inbred Dahl ; Hypertension, Renal ; Kidney ; Hypertension/complications ; Hypertension/genetics ; Blood Pressure ; RNA, Messenger ; Sodium Chloride, Dietary
Chemical Substances	Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Sodium Chloride (451W47IQ8X) ; RNA, Messenger ; Sodium Chloride, Dietary
Language	English
Publishing date	2023-07-07
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2023.06.031
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Zs.A 797: Show issues

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Article ; Online: Endothelial cells overexpressing CXCR1/2 are renoprotective in rats with acute kidney injury.

Xing, Dongqi / Hage, Fadi G / Feng, Wenguang / Guo, Yuanyuan / Oparil, Suzanne / Sanders, Paul W

American journal of physiology. Renal physiology

2023 Volume 324, Issue 4, Page(s) F374–F386

Abstract: Inflammation that develops with the release of chemokines and cytokines during acute kidney injury (AKI) has been shown to participate in functional renal recovery. Although a major research focus has been on the role of macrophages, the family of C-X-C ... ...

Abstract	Inflammation that develops with the release of chemokines and cytokines during acute kidney injury (AKI) has been shown to participate in functional renal recovery. Although a major research focus has been on the role of macrophages, the family of C-X-C motif chemokines that promote neutrophil adherence and activation also increases with kidney ischemia-reperfusion (I/R) injury. This study tested the hypothesis that intravenous delivery of endothelial cells (ECs) that overexpress (C-X-C motif) chemokine receptors 1 and 2 (CXCR1 and CXCR2, respectively) improves outcomes in kidney I/R injury. Overexpression of CXCR1/2 enhanced homing of endothelial cells to I/R-injured kidneys and limited interstitial fibrosis, capillary rarefaction, and tissue injury biomarkers (serum creatinine concentration and urinary kidney injury molecule-1) following AKI and also reduced expression of P-selectin and the rodent (C-X-C motif) chemokine cytokine-induced neutrophil chemoattractant (CINC)-2β as well as the number of myeloperoxidase-positive cells in the postischemic kidney. The serum chemokine/cytokine profile, including CINC-1, showed similar reductions. These findings were not observed in rats given endothelial cells transduced with an empty adenoviral vector (null-ECs) or a vehicle alone. These data indicate that extrarenal endothelial cells that overexpress CXCR1 and CXCR2, but not null-ECs or vehicle alone, reduce I/R kidney injury and preserve kidney function in a rat model of AKI.
MeSH term(s)	Rats ; Animals ; Endothelial Cells/metabolism ; Microvascular Rarefaction/pathology ; Acute Kidney Injury/pathology ; Chemokines/metabolism ; Inflammation/metabolism ; Cytokines/metabolism ; Kidney/metabolism ; Receptors, Chemokine/metabolism ; Fibrosis ; Reperfusion Injury/pathology
Chemical Substances	Chemokines ; Cytokines ; Receptors, Chemokine
Language	English
Publishing date	2023-02-16
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00238.2022
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Uc I Zs.89: Show issues

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Article ; Online: The Proximal Tubule Toxicity of Immunoglobulin Light Chains.

Sirac, Christophe / Batuman, Vecihi / Sanders, Paul W

Kidney international reports

2021 Volume 6, Issue 5, Page(s) 1225–1231

Abstract: Plasma and B cells dyscrasias that overproduce monoclonal immunoglobulin free light chains (FLCs) affect the kidney frequently in various ways. The hematologic dyscrasia responsible for the production of FLCs may or may not meet the criteria for cancer, ... ...

Abstract	Plasma and B cells dyscrasias that overproduce monoclonal immunoglobulin free light chains (FLCs) affect the kidney frequently in various ways. The hematologic dyscrasia responsible for the production of FLCs may or may not meet the criteria for cancer, such as multiple myeloma (MM) or lymphoma, or may remain subclinical. If there is overt malignancy, the accompanying kidney disorder is called myeloma- or lymphoma-associated. If the dyscrasia is subclinical, the associated kidney disorders are grouped as monoclonal gammopathy of renal significance. Glomeruli and tubules may both be involved. The proximal tubule disorders comprise a spectrum of interesting syndromes, which range in severity. This review focuses on the recent insights gained into the patterns and the mechanisms of proximal tubule toxicity of FLCs, including subtle transport disorders, such as proximal tubule acidosis, partial or complete Fanconi syndrome, or severe acute or chronic renal failure. Histologically, there may be crystal deposition in the proximal tubule cells, acute tubule injury, interstitial inflammation, fibrosis, and tubule atrophy. Specific structural alterations in the V domain of FLCs caused by somatic hypermutations are responsible for crystal formation as well as partial or complete Fanconi syndrome. Besides crystal formation, tubulointerstitial inflammation and proximal tubulopathy can be mediated by direct activation of inflammatory pathways through cytokines and Toll-like receptors due to cell stress responses induced by excessive FLC endocytosis into the proximal tubule cells. Therapy directed against the clonal source of the toxic light chain can prevent progression to more severe lesions and may help preserve kidney function.
Language	English
Publishing date	2021-03-03
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2021.02.026
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Article ; Online: Cellular antioxidant mechanisms control immunoglobulin light chain-mediated proximal tubule injury.

Ying, Kai Er / Feng, Wenguang / Ying, Wei-Zhong / Sanders, Paul W

Free radical biology & medicine

2021 Volume 171, Page(s) 80–90

Abstract: A major cause of morbidity and mortality in multiple myeloma is kidney injury from overproduction of monoclonal immunoglobulin light chains (FLC). FLC can induce damage through the production of hydrogen peroxide, which activates pro-inflammatory and pro- ...

Abstract	A major cause of morbidity and mortality in multiple myeloma is kidney injury from overproduction of monoclonal immunoglobulin light chains (FLC). FLC can induce damage through the production of hydrogen peroxide, which activates pro-inflammatory and pro-apoptotic pathways. The present study focused on catalase, a highly conserved antioxidant enzyme that degrades hydrogen peroxide. Initial findings were that FLC increased hydrogen peroxide levels but also decreased catalase levels and activity in proximal tubule epithelium. In order to clarify, we showed that the phosphatidylinositol 3-kinase inhibitor, LY294002, inhibited FLC-induced Akt-mediated deactivation of Forkhead box O class 3a (FoxO3a) and increased catalase activity in proximal tubule cells. Augmented catalase activity decreased FLC-mediated production of hydrogen peroxide as well as the associated increase in High Mobility Group Box 1 (HMGB1) protein release and caspase-3 activity. Coincubation of cells with FLC and an allosteric activator of Sirtuin 1 (SIRT1) was also sufficient to increase catalase activity and promote similar cytoprotective effects. Our studies confirmed that the mechanism of downregulation of catalase by FLC involved deactivation of FoxO3a and inhibition of SIRT1. Mechanistic understanding of catalase regulation allows for future treatments that target pathways that increase catalase in the setting of proximal tubule injury from FLC.
MeSH term(s)	Antioxidants ; Catalase ; Hydrogen Peroxide ; Immunoglobulin Light Chains ; Kidney Tubules, Proximal
Chemical Substances	Antioxidants ; Immunoglobulin Light Chains ; Hydrogen Peroxide (BBX060AN9V) ; Catalase (EC 1.11.1.6)
Language	English
Publishing date	2021-05-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2021.05.011
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Zs.A 2109: Show issues

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Article ; Online: Insights into the Uptake, Distribution, and Metabolism of 3-Isobutyl-2-hydroxypyrazine in Grapevine Using a Stable Isotope Tracer.

Sanders, Ross D / Boss, Paul K / Capone, Dimitra L / Kidman, Catherine M / Maffei, Sue M / Jeffery, David W

Journal of agricultural and food chemistry

2023 Volume 71, Issue 17, Page(s) 6717–6726

Abstract: Methoxypyrazines (MPs) are potent aroma compounds that have been predominately studied in grape berries but can also be detected in other vine tissues. The synthesis of MPs in berries from hydroxypyrazines by VvOMT3 is well established, but the origin of ...

Abstract	Methoxypyrazines (MPs) are potent aroma compounds that have been predominately studied in grape berries but can also be detected in other vine tissues. The synthesis of MPs in berries from hydroxypyrazines by VvOMT3 is well established, but the origin of MPs in vine tissues that have negligible
MeSH term(s)	Wine/analysis ; Tandem Mass Spectrometry ; Vitis/chemistry ; Pyrazines/analysis ; Fruit/chemistry
Chemical Substances	3-isobutyl-2-hydroxypyrazine ; Pyrazines
Language	English
Publishing date	2023-04-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	241619-0
ISSN	1520-5118 ; 0021-8561
ISSN (online)	1520-5118
ISSN	0021-8561
DOI	10.1021/acs.jafc.3c00306
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Zs.A 1172: Show issues

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Article: In meeting the increasing demands for total knee arthroplasty, can we achieve high levels of quality care in a small community hospital? A mixed-methods study.

Sanders, Ethan B / Dobransky, Johanna S / Chen, Brian P / Bodrogi, Andrew W / Beaulé, Paul E / Poitras, Stéphane

Frontiers in surgery

2023 Volume 10, Page(s) 998301

Abstract: Purpose: Small community hospitals (SCHs) help meet the demand for total knee arthroplasty (TKA). This mixed-methods study compares outcomes and analyses of environmental differences following TKA at a SCH and a tertiary care hospital (TCH).: Methods!# ...

Abstract	Purpose: Small community hospitals (SCHs) help meet the demand for total knee arthroplasty (TKA). This mixed-methods study compares outcomes and analyses of environmental differences following TKA at a SCH and a tertiary care hospital (TCH). Methods: Quantitative Results: Quantitative Conclusion: Given the increasing demand for TKA, the SCH represents a viable option to increase capacity, while reducing LOS. Future directions to reduce LOS include addressing social barriers to discharge and patient prioritization for assessment by allied health services. When TKA is performed by the same set of surgeons, the SCH provides quality care with a shorter LOS and comparable with urban hospitals, and this can be attributed to the differences in resource utilization in the two hospital settings.
Language	English
Publishing date	2023-02-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2773823-1
ISSN	2296-875X
ISSN	2296-875X
DOI	10.3389/fsurg.2023.998301
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Article ; Online: Rootstock, Vine Vigor, and Light Mediate Methoxypyrazine Concentrations in the Grape Bunch Rachis of

Sanders, Ross D / Boss, Paul K / Capone, Dimitra L / Kidman, Catherine M / Bramley, Robert G V / Nicholson, Emily L / Jeffery, David W

Journal of agricultural and food chemistry

2022 Volume 70, Issue 17, Page(s) 5417–5426

Abstract: Ramsey rootstock has previously been implicated in an approximate 8-fold increase of 3-isobutyl-2-methoxypyrazine (IBMP) levels in the rachis (grape bunch stem) ... ...

Abstract	Ramsey rootstock has previously been implicated in an approximate 8-fold increase of 3-isobutyl-2-methoxypyrazine (IBMP) levels in the rachis (grape bunch stem) of
MeSH term(s)	Fruit ; Vitis ; Wine/analysis
Language	English
Publishing date	2022-04-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	241619-0
ISSN	1520-5118 ; 0021-8561
ISSN (online)	1520-5118
ISSN	0021-8561
DOI	10.1021/acs.jafc.1c07978
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Zs.A 1172: Show issues

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Article ; Online: Atrial fibrillation progression after cryoablation vs. radiofrequency ablation: the CIRCA-DOSE trial.

Andrade, Jason G / Deyell, Marc W / Khairy, Paul / Champagne, Jean / Leong-Sit, Peter / Novak, Paul / Sterns, Lawrence / Roux, Jean-Francois / Sapp, John / Bennett, Richard / Bennett, Matthew / Hawkins, Nathaniel / Sanders, Prashanthan / Macle, Laurent

European heart journal

2023 Volume 45, Issue 7, Page(s) 510–518

Abstract: Background and aims: Atrial fibrillation (AF) is a chronic progressive disorder. Persistent forms of AF are associated with increased rates of thromboembolism, heart failure, and death. Catheter ablation modifies the pathogenic mechanism of AF ... ...

Abstract	Background and aims: Atrial fibrillation (AF) is a chronic progressive disorder. Persistent forms of AF are associated with increased rates of thromboembolism, heart failure, and death. Catheter ablation modifies the pathogenic mechanism of AF progression. No randomized studies have evaluated the impact of the ablation energy on progression to persistent atrial tachyarrhythmia. Methods: Three hundred forty-six patients with drug-refractory paroxysmal AF were enrolled and randomly assigned to contact-force-guided RF ablation (CF-RF ablation, 115), 4 min cryoballoon ablation (CRYO-4, 115), or 2 min cryoballoon ablation (CRYO-2, 116). Implantable cardiac monitors placed at study entry were used for follow-up. The main outcome was the first episode of persistent atrial tachyarrhythmia. Secondary outcomes included atrial tachyarrhythmia recurrence and arrhythmia burden on the implantable monitor. Results: At a median of 944.0 (interquartile range [IQR], 612.5-1104) days, 0 of 115 patients (0.0%) randomly assigned to CF-RF, 8 of 115 patients (7.0%) assigned to CRYO-4, and 5 of 116 patients (4.3%) assigned to CRYO-2 experienced an episode of persistent atrial tachyarrhythmia (P = .03). A documented recurrence of any atrial tachyarrhythmia ≥30 s occurred in 56.5%, 53.9%, and 62.9% of those randomized to CF-RF, CRYO-4, and CRYO-2, respectively; P = .65. Compared with that of the pre-ablation monitoring period, AF burden was reduced by a median of 99.5% (IQR 94.0%, 100.0%) with CF-RF, 99.9% (IQR 93.3%-100.0%) with CRYO-4, and 99.1%% (IQR 87.0%-100.0%) with CRYO-2 (P = .38). Conclusions: Catheter ablation of paroxysmal AF using radiofrequency energy was associated with fewer patients developing persistent AF on follow-up.
MeSH term(s)	Humans ; Atrial Fibrillation/surgery ; Cryosurgery/adverse effects ; Treatment Outcome ; Catheter Ablation/adverse effects ; Tachycardia ; Recurrence ; Pulmonary Veins/surgery
Language	English
Publishing date	2023-08-25
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	603098-1
ISSN	1522-9645 ; 0195-668X
ISSN (online)	1522-9645
ISSN	0195-668X
DOI	10.1093/eurheartj/ehad572
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Zs.A 1563: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 640: Show issues

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Article ; Online: Mechanisms of light chain injury along the tubular nephron.

Sanders, Paul W

Journal of the American Society of Nephrology : JASN

2012 Volume 23, Issue 11, Page(s) 1777–1781

Abstract: The tubular nephron is responsible for reabsorption and catabolism of filtered low molecular weight proteins that include Ig free light chains. In the setting of a plasma cell dyscrasia, significant amounts of free light chains, now monoclonal proteins, ... ...

Abstract	The tubular nephron is responsible for reabsorption and catabolism of filtered low molecular weight proteins that include Ig free light chains. In the setting of a plasma cell dyscrasia, significant amounts of free light chains, now monoclonal proteins, present to the tubular nephron for disposal. The result may be clinical renal dysfunction in the form of AKI, progressive CKD, and end-stage kidney disease. Here, I review the mechanisms involved in these processes that result in tubular injury, including proximal tubulopathy and cast nephropathy.
MeSH term(s)	Acute Kidney Injury/etiology ; Acute Kidney Injury/immunology ; Fanconi Syndrome/etiology ; Fanconi Syndrome/immunology ; Humans ; Immunoglobulin Light Chains/chemistry ; Immunoglobulin Light Chains/metabolism ; Kidney Tubules/immunology ; Kidney Tubules/injuries ; Models, Molecular ; Nephrons/immunology ; Nephrons/injuries ; Renal Insufficiency, Chronic/etiology ; Renal Insufficiency, Chronic/immunology
Chemical Substances	Immunoglobulin Light Chains
Language	English
Publishing date	2012-09-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2012040388
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Zs.A 3344: Show issues

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Article ; Online: Dietary salt initiates redox signaling between endothelium and vascular smooth muscle through NADPH oxidase 4.

Ying, Kai Er / Feng, Wenguang / Ying, Wei-Zhong / Li, Xingsheng / Xing, Dongqi / Sun, Yong / Chen, Yabing / Sanders, Paul W

Redox biology

2022 Volume 52, Page(s) 102296

Abstract: Prevention of phenotype switching of vascular smooth muscle cells is an important determinant of normal vascular physiology. Hydrogen peroxide ( ... ...

Abstract	Prevention of phenotype switching of vascular smooth muscle cells is an important determinant of normal vascular physiology. Hydrogen peroxide (H
MeSH term(s)	Animals ; Core Binding Factor Alpha 1 Subunit/genetics ; Endothelium/metabolism ; Endothelium, Vascular/metabolism ; Hydrogen Peroxide/metabolism ; Mice ; Muscle, Smooth, Vascular/metabolism ; Myocytes, Smooth Muscle/metabolism ; NADPH Oxidase 1/metabolism ; NADPH Oxidase 4/genetics ; NADPH Oxidase 4/metabolism ; NADPH Oxidases/metabolism ; Osteogenesis ; Oxidation-Reduction ; Sodium Chloride ; Sodium Chloride, Dietary/metabolism
Chemical Substances	Core Binding Factor Alpha 1 Subunit ; Sodium Chloride, Dietary ; Sodium Chloride (451W47IQ8X) ; Hydrogen Peroxide (BBX060AN9V) ; NADPH Oxidase 1 (EC 1.6.3.-) ; NADPH Oxidase 4 (EC 1.6.3.-) ; NADPH Oxidases (EC 1.6.3.-)
Language	English
Publishing date	2022-03-24
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2022.102296
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