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Article ; Online: Bidirectional relation between dipeptidyl peptidase 4 and angiotensin II type I receptor signaling.

Martins, Flavia L / Ribeiro-Silva, Joao Carlos / Nistala, Ravi / Girardi, Adriana C C

American journal of physiology. Cell physiology

2024 Volume 326, Issue 4, Page(s) C1203–C1211

Abstract: Cardiometabolic diseases are often associated with heightened levels of angiotensin II (Ang II), which accounts for the observed oxidative stress, inflammation, and fibrosis. Accumulating evidence indicates a parallel upregulation of dipeptidyl ... ...

Abstract	Cardiometabolic diseases are often associated with heightened levels of angiotensin II (Ang II), which accounts for the observed oxidative stress, inflammation, and fibrosis. Accumulating evidence indicates a parallel upregulation of dipeptidyl dipeptidase 4 (DPP4) activity in cardiometabolic diseases, with its inhibition shown to mitigate oxidative stress, inflammation, and fibrosis. These findings highlight an overlap between the pathophysiological mechanisms used by Ang II and DPP4. Recent evidence demonstrates that targeted inhibition of DPP4 prevents the rise in Ang II and its associated molecules in experimental models of cardiometabolic diseases. Similarly, inhibitors of the angiotensin I-converting enzyme (ACE) or Ang II type 1 receptor (AT1R) blockers downregulate DPP4 activity, establishing a bidirectional relationship between DPP4 and Ang II. Here, we discuss the current evidence supporting the cross talk between Ang II and DPP4, along with the potential mechanisms promoting this cross regulation. A comprehensive analysis of this bidirectional relationship across tissues will advance our understanding of how DPP4 and Ang II collectively promote the development and progression of cardiometabolic diseases.
MeSH term(s)	Humans ; Angiotensin II ; Dipeptidyl Peptidase 4 ; Peptidyl-Dipeptidase A ; Receptor, Angiotensin, Type 1 ; Inflammation ; Fibrosis ; Cardiovascular Diseases ; Angiotensin I
Chemical Substances	Angiotensin II (11128-99-7) ; Dipeptidyl Peptidase 4 (EC 3.4.14.5) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Receptor, Angiotensin, Type 1 ; Angiotensin I (9041-90-1)
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00734.2023
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Article ; Online: Dipeptidylpeptidase 4 promotes survival and stemness of acute myeloid leukemia stem cells.

Wang, Chen / Nistala, Ravi / Cao, Min / Pan, Yi / Behrens, Madelaine / Doll, Donald / Hammer, Richard D / Nistala, Puja / Chang, Hui-Ming / Yeh, Edward T H / Kang, XunLei

Cell reports

2023 Volume 42, Issue 2, Page(s) 112105

Abstract: Leukemic-stem-cell-specific targeting may improve the survival of patients with acute myeloid leukemia (AML) by avoiding the ablative effects of standard regimens on normal hematopoiesis. Herein, we perform an unbiased screening of compounds targeting ... ...

Abstract	Leukemic-stem-cell-specific targeting may improve the survival of patients with acute myeloid leukemia (AML) by avoiding the ablative effects of standard regimens on normal hematopoiesis. Herein, we perform an unbiased screening of compounds targeting cell surface proteins and identify clinically used DPP4 inhibitors as strong suppressors of AML development in both murine AML models and primary human AML cells xenograft model. We find in retrovirus-induced AML mouse models that DPP4-deficient AML cell-transplanted mice exhibit delay and reversal of AML development, whereas deletion of DPP4 has no significant effect on normal hematopoiesis. DPP4 activates and sustains survival of AML stem cells that are critical for AML development in both human and animal models via binding with Src kinase and activation of nuclear factor κB (NF-κB) signaling. Thus, inhibition of DPP4 is a potential therapeutic strategy against AML development through suppression of survival and stemness of AML cells.
MeSH term(s)	Animals ; Humans ; Mice ; Dipeptidyl Peptidase 4/metabolism ; Disease Models, Animal ; Leukemia, Myeloid, Acute/metabolism ; Signal Transduction ; Stem Cells/metabolism
Chemical Substances	Dipeptidyl Peptidase 4 (EC 3.4.14.5) ; DPP4 protein, human (EC 3.4.14.5) ; Dpp4 protein, mouse (EC 3.4.14.5)
Language	English
Publishing date	2023-02-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112105
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Article ; Online: Recent advances in wearable sensors and data analytics for continuous monitoring and analysis of biomarkers and symptoms related to COVID-19.

Li, Huijie / Yuan, Jianhe / Fennell, Gavin / Abdulla, Vagif / Nistala, Ravi / Dandachi, Dima / Ho, Dominic K C / Zhang, Yi

Biophysics reviews

2023 Volume 4, Issue 3, Page(s) 31302

Abstract: The COVID-19 pandemic has changed the lives of many people around the world. Based on the available data and published reports, most people diagnosed with COVID-19 exhibit no or mild symptoms and could be discharged home for self-isolation. Considering ... ...

Abstract	The COVID-19 pandemic has changed the lives of many people around the world. Based on the available data and published reports, most people diagnosed with COVID-19 exhibit no or mild symptoms and could be discharged home for self-isolation. Considering that a substantial portion of them will progress to a severe disease requiring hospitalization and medical management, including respiratory and circulatory support in the form of supplemental oxygen therapy, mechanical ventilation, vasopressors, etc. The continuous monitoring of patient conditions at home for patients with COVID-19 will allow early determination of disease severity and medical intervention to reduce morbidity and mortality. In addition, this will allow early and safe hospital discharge and free hospital beds for patients who are in need of admission. In this review, we focus on the recent developments in next-generation wearable sensors capable of continuous monitoring of disease symptoms, particularly those associated with COVID-19. These include wearable non/minimally invasive biophysical (temperature, respiratory rate, oxygen saturation, heart rate, and heart rate variability) and biochemical (cytokines, cortisol, and electrolytes) sensors, sensor data analytics, and machine learning-enabled early detection and medical intervention techniques. Together, we aim to inspire the future development of wearable sensors integrated with data analytics, which serve as a foundation for disease diagnostics, health monitoring and predictions, and medical interventions.
Language	English
Publishing date	2023-07-19
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2688-4089
ISSN (online)	2688-4089
DOI	10.1063/5.0140900
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Article ; Online: Diabetes, hypertension, and chronic kidney disease progression: role of DPP4.

Nistala, Ravi / Savin, Virginia

American journal of physiology. Renal physiology

2017 Volume 312, Issue 4, Page(s) F661–F670

Abstract: The protein dipeptidyl peptidase 4 (DPP4) is a target in diabetes management and reduction of associated cardiovascular risk. Inhibition of the enzymatic function and genetic deletion of DPP4 is associated with tremendous benefits to the heart, ... ...

Abstract	The protein dipeptidyl peptidase 4 (DPP4) is a target in diabetes management and reduction of associated cardiovascular risk. Inhibition of the enzymatic function and genetic deletion of DPP4 is associated with tremendous benefits to the heart, vasculature, adipose tissue, and the kidney in rodent models of obesity, diabetes and hypertension, and associated complications. The recently concluded, "Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53" trial revealed a reduction in proteinuria in chronic kidney disease patients (stages 1-3). These results have spurred immense interest in the nonenzymatic and enzymatic role of DPP4 in the kidney. DPP4 is expressed predominantly in the glomeruli and S1-S3 segments of the nephron and to a lesser extent in other segments. DPP4 is known to facilitate absorption of cleaved dipeptides and regulate the function of the sodium/hydrogen exchanger-3 in the proximal tubules. DPP4, also known as CD26, has an important role in costimulation of lymphocytes via caveolin-1 on antigen-presenting cells in peripheral blood. Herein, we present our perspectives for the ongoing interest in the role of DPP4 in the kidney.
MeSH term(s)	Animals ; Antigen-Presenting Cells/enzymology ; Antigen-Presenting Cells/immunology ; Caveolin 1/metabolism ; Diabetes Mellitus/drug therapy ; Diabetes Mellitus/enzymology ; Diabetes Mellitus/immunology ; Diabetes Mellitus/physiopathology ; Diabetic Nephropathies/drug therapy ; Diabetic Nephropathies/enzymology ; Diabetic Nephropathies/immunology ; Diabetic Nephropathies/physiopathology ; Dipeptidyl Peptidase 4/metabolism ; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use ; Disease Progression ; Humans ; Hypertension/drug therapy ; Hypertension/enzymology ; Hypertension/immunology ; Hypertension/physiopathology ; Kidney/drug effects ; Kidney/enzymology ; Kidney/immunology ; Kidney/physiopathology ; Lymphocyte Activation ; Renal Insufficiency, Chronic/drug therapy ; Renal Insufficiency, Chronic/enzymology ; Renal Insufficiency, Chronic/immunology ; Renal Insufficiency, Chronic/physiopathology ; Signal Transduction ; Sodium-Hydrogen Exchanger 3 ; Sodium-Hydrogen Exchangers/metabolism
Chemical Substances	Caveolin 1 ; Dipeptidyl-Peptidase IV Inhibitors ; Sodium-Hydrogen Exchanger 3 ; Sodium-Hydrogen Exchangers ; Dipeptidyl Peptidase 4 (EC 3.4.14.5)
Language	English
Publishing date	2017-04-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00316.2016
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Article ; Online: Microneedle-Based Potentiometric Sensing System for Continuous Monitoring of Multiple Electrolytes in Skin Interstitial Fluids.

Li, Huijie / Wu, Guangfu / Weng, Zhengyan / Sun, He / Nistala, Ravi / Zhang, Yi

ACS sensors

2021 Volume 6, Issue 6, Page(s) 2181–2190

Abstract: Electrolytes play a pivotal role in regulating cardiovascular functions, hydration, and muscle activation. The current standards for monitoring electrolytes involve periodic sampling of blood and measurements using laboratory techniques, which are often ... ...

Abstract	Electrolytes play a pivotal role in regulating cardiovascular functions, hydration, and muscle activation. The current standards for monitoring electrolytes involve periodic sampling of blood and measurements using laboratory techniques, which are often uncomfortable/inconvenient to the subjects and add considerable expense to the management of their underlying disease conditions. The wide range of electrolytes in skin interstitial fluids (ISFs) and their correlations with those in plasma create exciting opportunities for applications such as electrolyte and circadian metabolism monitoring. However, it has been challenging to monitor these electrolytes in the skin ISFs. In this study, we report a minimally invasive microneedle-based potentiometric sensing system for multiplexed and continuous monitoring of Na
MeSH term(s)	Biosensing Techniques ; Electrolytes ; Extracellular Fluid ; Needles ; Potentiometry
Chemical Substances	Electrolytes
Language	English
Publishing date	2021-05-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	2379-3694
ISSN (online)	2379-3694
DOI	10.1021/acssensors.0c02330
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Article ; Online: Repair of Limb Ischemia Is Dependent on Hematopoietic Stem Cell Specific-SHP-1 Regulation of TGF-β1.

Wang, Chen / Nistala, Ravi / Cao, Min / Li, De-Pei / Pan, Yi / Golzy, Mojgan / Cui, Yuqi / Liu, Zhenguo / Kang, XunLei

Arteriosclerosis, thrombosis, and vascular biology

2022 Volume 43, Issue 1, Page(s) 92–108

Abstract: Background: Hematopoietic stem cell (HSC) therapy has shown promise for tissue regeneration after ischemia. Therefore, there is a need to understand mechanisms underlying endogenous HSCs activation in response to ischemic stress and coordination of ... ...

Abstract	Background: Hematopoietic stem cell (HSC) therapy has shown promise for tissue regeneration after ischemia. Therefore, there is a need to understand mechanisms underlying endogenous HSCs activation in response to ischemic stress and coordination of angiogenesis and repair. SHP-1 plays important roles in HSC quiescence and differentiation by regulation of TGF-β1 signaling. TGF-β1 promotes angiogenesis by stimulating stem cells to secrete growth factors to initiate the formation of blood vessels and later aid in their maturation. We propose that SHP-1 responds to ischemia stress in HSC and progenitor cells (HSPC) via regulation of TGF-β1. Methods: A mouse hind limb ischemia model was used. Local blood perfusion in the limbs was determined using laser doppler perfusion imaging. The number of positive blood vessels per square millimeter, as well as blood vessel diameter (μm) and area (μm Results: After femoral artery ligation, TGF-β1 was initially decreased in the bone marrow by day 3 of ischemia, followed by an increase on day 7. This pattern was opposite to that in the peripheral blood, which is concordant with the response of HSC to ischemic stress. In contrast, SHP-1 deficiency in HSC is associated with irreversible activation of HSPCs in the bone marrow and increased circulating HSPCs in peripheral blood following limb ischemia. In addition, there was augmented auto-induction of TGF-β1 and sustained inactivation of SHP-1-Smad2 signaling, which impacted TGF-β1 expression in HSPCs in circulation. Importantly, restoration of normal T GF-β1 oscillations helped in the recovery of limb repair and function. Conclusions: HSPC-SHP-1-mediated regulation of TGF-β1 in both bone marrow and peripheral blood is required for a normal response to ischemic stress.
MeSH term(s)	Mice ; Animals ; Transforming Growth Factor beta1/metabolism ; Hematopoietic Stem Cells/metabolism ; Ischemia ; Lower Extremity
Chemical Substances	Transforming Growth Factor beta1 ; PTPN6 protein, human (EC 3.1.3.48)
Language	English
Publishing date	2022-11-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.122.318205
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Article ; Online: Tissue-specific expression of GLP1R in mice: is the problem of antibody nonspecificity solved?

Aroor, Annayya / Nistala, Ravi

Diabetes

2014 Volume 63, Issue 4, Page(s) 1182–1184

MeSH term(s)	Animals ; Glucagon-Like Peptide-1 Receptor ; Receptors, Glucagon/biosynthesis
Chemical Substances	Glp1r protein, mouse ; Glucagon-Like Peptide-1 Receptor ; Receptors, Glucagon
Language	English
Publishing date	2014-04
Publishing country	United States
Document type	Comment ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/db13-1937
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Article: Editorial: The Tribute of Physiology for the Understanding of COVID-19 Disease.

Lefthériotis, Georges / Wray, Susan / Girardi, Adriana Castello Costa / Vidal-Petiot, Emmanuelle / Bailey, Matthew A / Schechtman, Deborah / Ravi, Nistala / Noble, Denis

Frontiers in physiology

2021 Volume 12, Page(s) 761644

Language	English
Publishing date	2021-09-27
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2021.761644
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Article ; Online: Is there a role for the incretin system in blood pressure regulation?

Rao, Akhilesh / Nistala, Ravi

Current hypertension reports

2014 Volume 16, Issue 3, Page(s) 417

Abstract: Incretin-based therapies are now well established for diabetes management and are among the frontline agents for control of hyperglycemia. In addition to their antihyperglycemic effects, evidence is emerging on the role of these agents on blood pressure ... ...

Abstract	Incretin-based therapies are now well established for diabetes management and are among the frontline agents for control of hyperglycemia. In addition to their antihyperglycemic effects, evidence is emerging on the role of these agents on blood pressure regulation, cardioprotective and renoprotective properties. Because of the pleiotropic nature of these affects, these agents could offer significant benefits with regards to the cardiorenal metabolic complications that are part of the diabetes and obesity epidemic in the United States and worldwide. We review the various known mechanisms or pathways by which incretin based therapy exerts its regulation of blood pressure with emphasis on novel mechanisms such as inflammation/immunomodulation and oxidative stress.
MeSH term(s)	Animals ; Blood Pressure/drug effects ; Blood Pressure/immunology ; Dipeptidyl-Peptidase IV Inhibitors/therapeutic use ; Exenatide ; Glucagon-Like Peptide 1/agonists ; Humans ; Hypertension/drug therapy ; Incretins/immunology ; Incretins/therapeutic use ; Oxidative Stress ; Peptides/immunology ; Peptides/therapeutic use ; Pyrazines/immunology ; Pyrazines/therapeutic use ; Renin-Angiotensin System/drug effects ; Sitagliptin Phosphate ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology ; Triazoles/immunology ; Triazoles/therapeutic use ; Venoms/immunology ; Venoms/therapeutic use
Chemical Substances	Dipeptidyl-Peptidase IV Inhibitors ; Incretins ; Peptides ; Pyrazines ; Triazoles ; Venoms ; Glucagon-Like Peptide 1 (89750-14-1) ; Exenatide (9P1872D4OL) ; Sitagliptin Phosphate (TS63EW8X6F)
Language	English
Publishing date	2014-02-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2057367-4
ISSN	1534-3111 ; 1522-6417
ISSN (online)	1534-3111
ISSN	1522-6417
DOI	10.1007/s11906-013-0417-5
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Zs.A 5522: Show issues

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Article ; Online: mTORC1 inhibitors rapamycin and metformin affect cardiovascular markers differentially in ZDF rats.

Nistala, Ravi / Raja, Ahmad / Pulakat, Lakshmi

Canadian journal of physiology and pharmacology

2017 Volume 95, Issue 3, Page(s) 281–287

Abstract: Mammalian target for rapamycin complex 1 (mTORC1) is a common target for the action of immunosuppressant macrolide rapamycin and glucose-lowering metformin. Inhibition of mTORC1 can exert both beneficial and detrimental effects in different pathologies. ... ...

Abstract	Mammalian target for rapamycin complex 1 (mTORC1) is a common target for the action of immunosuppressant macrolide rapamycin and glucose-lowering metformin. Inhibition of mTORC1 can exert both beneficial and detrimental effects in different pathologies. Here, we investigated the differential effects of rapamycin (1.2 mg/kg per day delivered subcutaneously for 6 weeks) and metformin (300 mg/kg per day delivered orally for 11 weeks) treatments on male Zucker diabetic fatty (ZDF) rats that mimic the cardiorenal pathology of type 2 diabetic patients and progress to insulin insufficiency. Rapamycin and metformin improved proteinuria, and rapamycin also reduced urinary gamma glutamyl transferase (GGT) indicating improvement of tubular health. Metformin reduced food and water intake, and urinary sodium and potassium, whereas rapamycin increased urinary sodium. Metformin reduced plasma alkaline phosphatase, but induced transaminitis as evidenced by significant increases in plasma AST and ALT. Metformin also induced hyperinsulinemia, but did not suppress fasting plasma glucose after ZDF rats reached 17 weeks of age, and worsened lipid profile. Rapamycin also induced mild transaminitis. Additionally, both rapamycin and metformin increased plasma uric acid and creatinine, biomarkers for cardiovascular and renal disease. These observations define how rapamycin and metformin differentially modulate metabolic profiles that regulate cardiorenal pathology in conditions of severe type 2 diabetes.
MeSH term(s)	Animals ; Biomarkers/blood ; Biomarkers/urine ; Cardiovascular Diseases/blood ; Cardiovascular Diseases/enzymology ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/prevention & control ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/enzymology ; Diabetic Nephropathies/enzymology ; Diabetic Nephropathies/etiology ; Diabetic Nephropathies/prevention & control ; Disease Models, Animal ; Disease Progression ; Hypoglycemic Agents/pharmacology ; Insulin Resistance ; Liver/drug effects ; Liver/enzymology ; Male ; Mechanistic Target of Rapamycin Complex 1 ; Metformin/pharmacology ; Multiprotein Complexes/antagonists & inhibitors ; Multiprotein Complexes/metabolism ; Protein Kinase Inhibitors/pharmacology ; Proteinuria/enzymology ; Proteinuria/etiology ; Proteinuria/prevention & control ; Rats, Zucker ; Signal Transduction/drug effects ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; TOR Serine-Threonine Kinases/metabolism ; Time Factors
Chemical Substances	Biomarkers ; Hypoglycemic Agents ; Multiprotein Complexes ; Protein Kinase Inhibitors ; Metformin (9100L32L2N) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2017-01-04
Publishing country	Canada
Document type	Comparative Study ; Journal Article
ZDB-ID	127527-6
ISSN	1205-7541 ; 0008-4212
ISSN (online)	1205-7541
ISSN	0008-4212
DOI	10.1139/cjpp-2016-0567
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