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Lee PWT, Kobayashi M, Dohkai T, Takahashi I, Yoshida T, Harada H. 2-Oxoglutarate-dependent dioxygenases as oxygen sensors: their importance in health and disease. J Biochem 2025; 177:79-104. [PMID: 39679914 DOI: 10.1093/jb/mvae087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 10/22/2024] [Accepted: 12/06/2024] [Indexed: 12/17/2024] Open
Abstract
Since low oxygen conditions below physiological levels, hypoxia, are associated with various diseases, it is crucial to understand the molecular basis behind cellular response to hypoxia. Hypoxia-inducible factors (HIFs) have been revealed to primarily orchestrate the hypoxic response at the transcription level and have continuously attracted great attention over the past three decades. In addition to these hypoxia-responsive effector proteins, 2-oxoglutarate-dependent dioxygenase (2-OGDD) superfamily including prolyl-4-hydroxylase domain-containing proteins (PHDs) and factor inhibiting HIF-1 (FIH-1) has attracted even greater attention in recent years as factors that act as direct oxygen sensors due to their necessity of oxygen for the regulation of the expression and activity of the regulatory subunit of HIFs. Herein, we present a detailed classification of 2-OGDD superfamily proteins, such as Jumonji C-domain-containing histone demethylases, ten-eleven translocation enzymes, AlkB family of DNA/RNA demethylases and lysyl hydroxylases, and discuss their specific functions and associations with various diseases. By introducing the multifaceted roles of 2-OGDD superfamily proteins in the hypoxic response, this review aims to summarize the accumulated knowledge about the complex mechanisms governing cellular adaptation to hypoxia in various physiological and pathophysiological contexts.
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Affiliation(s)
- Peter W T Lee
- Laboratory of Cancer Cell Biology, Graduate School of Biostudies, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
- Department of Genome Repair Dynamics, Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
| | - Minoru Kobayashi
- Laboratory of Cancer Cell Biology, Graduate School of Biostudies, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
- Department of Genome Repair Dynamics, Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
| | - Takakuni Dohkai
- Laboratory of Cancer Cell Biology, Graduate School of Biostudies, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
| | - Itsuki Takahashi
- Laboratory of Cancer Cell Biology, Graduate School of Biostudies, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
| | - Takumi Yoshida
- Laboratory of Cancer Cell Biology, Graduate School of Biostudies, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
| | - Hiroshi Harada
- Laboratory of Cancer Cell Biology, Graduate School of Biostudies, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
- Department of Genome Repair Dynamics, Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
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Kishimoto S, Horie K, Devasahayam N, Yamashita K, Gadisetti C, Yamamoto K, Brender JR, Mitchell JB, Krishna MC, Linehan WM, Crooks DR. Low Field Magnetic Resonance Imaging to Detect Acute Kidney Injury. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.01.22.634393. [PMID: 39896573 PMCID: PMC11785171 DOI: 10.1101/2025.01.22.634393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2025]
Abstract
Renal oxygenation is essential for maintaining kidney function. Disruptions in oxygen delivery can lead to renal hypoxia, which can exacerbate kidney injury through multiple pathways, including inflammation, oxidative stress, and ischemia-reperfusion injury. Despite the recognized importance of oxygenation in renal pathology, non-invasive and reliable methods for assessing kidney oxygen levels are limited. Current techniques either lack sensitivity or involve invasive procedures, restricting their use in routine monitoring. Therefore, there is a pressing need for innovative approaches to assess renal oxygenation, particularly in kidney injury. This study evaluated Electron Paramagnetic Resonance (EPR)-based oxygen imaging using the paramagnetic tracer Ox071 to assess kidney oxygen levels in mice with cyclophosphamide-induced kidney injury. Urine pO2 was also assessed as a potential surrogate marker. EPR oximetry accurately measured kidney oxygen distribution, revealing a temporary increase in pO2 post-injury. Urine oximetry, however, did not reliably reflect changes in kidney oxygenation. Furthermore, EPR oximetry provided high-resolution spatial mapping of oxygen levels within the kidney, allowing for a detailed understanding of the impact of hypoxia on renal tissue. EPR oximetry is a promising, non-invasive tool for monitoring renal oxygenation, offering high-resolution mapping and longitudinal assessment. Its ability to provide detailed information about oxygen distribution within the kidney makes it a valuable tool for studying the pathophysiology of renal diseases and for developing novel therapeutic strategies.
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Affiliation(s)
- Shun Kishimoto
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
- Clinical Cancer Metabolism Facility, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
- Radiation Biology Branch, Center for Cancer Research, National Cancer Institute
| | - Kazumasa Horie
- Radiation Biology Branch, Center for Cancer Research, National Cancer Institute
| | | | - Kota Yamashita
- Radiation Biology Branch, Center for Cancer Research, National Cancer Institute
| | | | - Kazutoshi Yamamoto
- Radiation Biology Branch, Center for Cancer Research, National Cancer Institute
| | - Jeffrey R. Brender
- Radiation Biology Branch, Center for Cancer Research, National Cancer Institute
| | - James B. Mitchell
- Radiation Biology Branch, Center for Cancer Research, National Cancer Institute
| | - Murali C. Krishna
- Radiation Biology Branch, Center for Cancer Research, National Cancer Institute
| | - W. Marston Linehan
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
| | - Daniel R. Crooks
- Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
- Clinical Cancer Metabolism Facility, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
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Kawase K, Hamamoto S, Unno R, Taguchi K, Okada A, Yasui T. Prolyl hydroxylase domain inhibitors prevent kidney crystal formation by suppressing inflammation. Urolithiasis 2024; 53:16. [PMID: 39724472 DOI: 10.1007/s00240-024-01677-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 12/01/2024] [Indexed: 12/28/2024]
Abstract
The early stages of kidney crystal formation involve inflammation and hypoxia-induced cell injury; however, the role of the hypoxic response in kidney crystal formation remains unclear. This study investigated the effects of a prolyl hydroxylase domain inhibitor (roxadustat) on renal calcium oxalate (CaOx) crystal formation through in vitro and in vivo approaches. In the in vitro experiment, murine renal tubular cells (RTCs) were exposed to varying roxadustat concentrations and CaOx crystals. CaOx monohydrate (COM) crystal adhesion was evaluated using fluorescent labels, whereas western blotting was used to examine protein expression. Quantitative real-time polymerase chain reaction was used to analyze gene expression changes. Macrophage responses were investigated by co-culturing them with RTCs treated with COM. In the in vivo experiment, C57BL/6J mice were injected with roxadustat or saline for 2 days, followed by glyoxylate for 6 days to induce renal crystal deposition. Biochemical measurements recorded plasma erythropoietin, urinary data, and pH levels. Roxadustat suppressed the adhesion of COM crystals to RTCs and the expression of proinflammatory genes, such as chemokine (C-C motif) ligand 2 (Ccl2) and secreted phosphoprotein 1 (Spp1). Roxadustat decreased the expression levels of Ccl2, tumor necrosis factor (Tnf), and interleukin 6 (Il6) in co-cultured macrophages. In the in vivo experiment, the amount of renal CaOx crystal deposits was significantly lower in the roxadustat-treated group than in the vehicle group. Roxadustat treatment decreased Ccl2, Tnf, and adheision G protein-coupled receptor E1 (Adgre1) expression in the kidneys. Roxadustat reduced kidney inflammation and CaOx crystal deposition, suggesting its potential as a therapeutic option for kidney stone prevention.
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Affiliation(s)
- Kengo Kawase
- Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Japan
| | - Shuzo Hamamoto
- Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Japan.
| | - Rei Unno
- Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Japan
| | - Kazumi Taguchi
- Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Japan
| | - Atsushi Okada
- Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Japan
| | - Takahiro Yasui
- Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Japan
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van Hassel G, Groothof D, Douwes JM, Hoendermis ES, Liem ET, Willems TP, Ebels T, Voors AA, Bakker SJ, Berger RM, van Melle JP. Deterioration in Renal Function in Patients With a Fontan Circulation and Association With Mortality. JACC. ADVANCES 2024; 3:101399. [PMID: 39629062 PMCID: PMC11612357 DOI: 10.1016/j.jacadv.2024.101399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 09/22/2024] [Accepted: 10/01/2024] [Indexed: 12/06/2024]
Abstract
Background Renal dysfunction is a well-established risk factor in cardiovascular disease, but little is known about the prevalence and factors associated with deterioration in renal function in patients with a Fontan circulation. Objectives The purpose of the study was to investigate the course and factors associated with deterioration in renal function in patients with a Fontan circulation and its association with mortality. Methods This is a longitudinal study of patients with a Fontan circulation (n = 82), in which creatinine-based estimated glomerular filtration rate (eGFRcr) was measured over an 11-year time period. Cystatin C and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels were measured at baseline. Renal dysfunction was defined as an eGFR <90 ml/min/1.73 m2. Factors associated with annual change in eGFRcr were investigated with linear mixed-effect models and compared with data from a healthy Dutch cohort. The primary endpoint for the survival analyses was all-cause mortality. Associations between repeated eGFRcr levels and the primary endpoint were assessed using a joint model. Results The median age at baseline was 20 years (IQR: 14-27 years). Twelve percent of the cohort had renal dysfunction based on eGFRcr and 24% based on cystatin C-based eGFRcys. During follow-up, eGFRcr deteriorated on average by 1.36 ml/min/1.73 m2/year, which is faster than the healthy cohort. Higher baseline NT-proBNP z-scores were associated with a more rapid decline in eGFRcr. A larger decline in eGFRcr was associated with all-cause mortality. Conclusions Declines in eGFRcr in patients with Fontan circulation are more rapid than in healthy individuals. Higher baseline NT-proBNP z-scores are associated with a more rapid deterioration of eGFRcr, and eGFRcr deterioration is associated with mortality.
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Affiliation(s)
- Gaston van Hassel
- Center for Congenital Heart Diseases, Paediatric Cardiology, Beatrix Children’s Hospital, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Dion Groothof
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Johannes M. Douwes
- Center for Congenital Heart Diseases, Paediatric Cardiology, Beatrix Children’s Hospital, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Elke S. Hoendermis
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Eryn T. Liem
- Center for Congenital Heart Diseases, Paediatric Cardiology, Beatrix Children’s Hospital, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Tineke P. Willems
- Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Tjark Ebels
- Department of Cardiothoracic Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Adriaan A. Voors
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Stephan J.L. Bakker
- Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Rolf M.F. Berger
- Center for Congenital Heart Diseases, Paediatric Cardiology, Beatrix Children’s Hospital, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Joost P. van Melle
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
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Hassan AF, Gharib AF, Hagag HM, Ismail KA, Omran OM, Elamin EM, Atteia HH. Restoration of renal hemodynamics and functions by Nigella sativa administration in dinitrophenol-induced hypoxia in rat's animal model. Int J Health Sci (Qassim) 2024; 18:22-31. [PMID: 38974646 PMCID: PMC11226942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/09/2024] Open
Abstract
Objective Hypoxia is one of the principal causes of renal diseases. This study aimed to evaluate the effects of Nigella sativa on dinitrophenol (DNP)-induced hypoxia renal damage in rats. Methods Forty adult male rats were incorporated in this study. The rats were divided into four groups: control group, N. sativa group, DNP hypoxic group, and DNP + N. sativa group receiving N. sativa (400 mg/kg body weight). Serum and renal tissue erythropoietin (EPO) hormone and hypoxia-inducible factor-2α (HIF-2α) levels were measured. Renal oxidative stress biomarkers, inflammatory biomarkers, renal hemodynamics, and histopathological examination were evaluated. Results Administration of N. sativa highly significantly normalized serum EPO level, HIF-2α (P < 0.001 for each) in DNP + N. sativa treated rats as compared to DNP hypoxic rats. Furthermore, it highly significantly improved renal oxidative stress evident by decreased renal tissues malondialdehyde and increased superoxide dismutase, total thiol, and catalase activity (P < 0.001 for each). Furthermore, a highly significant decline of renal intercellular adhesion molecule-1, myeloperoxidase, and interleukin-6 was observed in DNP + N. sativa rats (P < 0.001 for each). Improvements in renal hemodynamics and kidney functions were also found after N. sativa administration (with P < 0.001 for all parameters). In addition, N. sativa treatment reduced renal histopathological changes of the DNP + N. sativa group. Our results were statistically analyzed using the Prism software package (GraphPad version 8.0). Conclusion N. sativa has an alleviating effect on DNP-induced hypoxia renal damage and can restore kidney functions in rats' animal models. These effects were through antioxidant, anti-inflammatory, and hemodynamic mechanisms.
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Affiliation(s)
- Asmaa F. Hassan
- Department of Physiology, College of Medicine, Taif University, Taif, Saudi Arabia
- Department of Physiology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Amal F. Gharib
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia
| | - Howaida M. Hagag
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia
- Department of Pathology, Faculty of Medicine, Al-Azer University, Naser City, Cario, Egypt
| | - Khadiga A. Ismail
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia
| | - Ola M. Omran
- Department of Pathology, College of Medicine, Qassim University, Buraidah, Qassim Region, Saudi Arabia
- Department of Pathology, Faculty of Medicine Assiut University, Assiut, Egypt
| | - Enshrah Modathir Elamin
- Department of Pathology, College of Medicine, Qassim University, Buraidah, Qassim Region, Saudi Arabia
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Korus J, Wydro M, Gołębiowski M, Krakowska K, Poznański P, Musiał K, Konieczny A, Augustyniak-Bartosik H, Stojanowski J, Kusztal MA, Gołębiowski T. Changes of Dissociative Properties of Hemoglobin in Patients with Chronic Kidney Disease. Diagnostics (Basel) 2024; 14:1219. [PMID: 38928635 PMCID: PMC11203233 DOI: 10.3390/diagnostics14121219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 06/01/2024] [Accepted: 06/05/2024] [Indexed: 06/28/2024] Open
Abstract
Background: The ability of hemoglobin to bind and dissociate oxygen is crucial in delivering oxygen to tissues and is influenced by a range of physiological states, compensatory mechanisms, and pathological conditions. This may be illustrated by the oxyhemoglobin dissociation curve (ODC). The key parameter for evaluating the oxygen affinity to hemoglobin is p50. The aim of this study was to evaluate the impact of hemodialysis on p50 in a group of patients with chronic kidney disease (CKD). An additional goal was to assess the correlation between p50 and the parameters of erythropoiesis, point-of-care testing (POCT), and other laboratory parameters. Methods: One hundred and eighty patients (106 male, 74 female), mean age 62.5 ± 17 years, with CKD stage G4 and G5 were enrolled in this cross-sectional study. Patients were divided into two groups, including 65 hemodialysis (HD) patients and 115 patients not receiving dialysis (non-HD). During the standard procedure of arteriovenous fistula creation, blood samples from the artery (A) and the vein (V) were taken for POCT. The causes of CKD, as well as demographic and comorbidity data, were obtained from medical records and direct interviews. Results: The weekly dose of erythropoietin was higher in HD patients than in non-HD patients (4914 ± 2253 UI vs. 403 ± 798 UI, p < 0.01), but hemoglobin levels did not differ between these groups. In the group of non-HD patients, more advanced metabolic acidosis (MA) was found, compared to the group with HD. In arterial and venosus blood samples, the non-HD group had significantly lower pH, pCO2 and HCO3-. This group had a higher proportion of individuals with MA with HCO3- < 22 mmol/L (42% vs. 24%, p < 0.01). The absolute difference of p50 in arterial and venous blood was determined using the formula Δp50 = (p50-A) - (p50-V). Δp50 was significantly higher in the HD group in comparison to non-HD (0.08 ± 2.05 mmHg vs. -0.66 ± 1.93 mmHg, p = 0,02). There was a negative correlation between pH and the p50 value in arterial (pH-A vs. p50-A, r = -0.56, p < 0.01) and venous blood (pH-V vs. p50-V, r = -0.45, p < 0.01). In non-HD patients, hemoglobin levels correlated negatively with p50 (r = -0.29, p < 0.01), whereas no significant relation was found in HD patients. Conclusions: The ODC in pre-dialysis CKD (non-HD) patients is shifted to the right due to MA, and this is an additional factor influencing erythropoiesis. Hemodialysis restores the natural differences in hemoglobin's dissociation characteristics in the arterial and venous circulation.
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Affiliation(s)
- Justyna Korus
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (J.K.); (M.W.); (M.G.); (K.K.); (P.P.); (A.K.); (H.A.-B.); (J.S.); (M.A.K.)
| | - Maria Wydro
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (J.K.); (M.W.); (M.G.); (K.K.); (P.P.); (A.K.); (H.A.-B.); (J.S.); (M.A.K.)
| | - Maciej Gołębiowski
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (J.K.); (M.W.); (M.G.); (K.K.); (P.P.); (A.K.); (H.A.-B.); (J.S.); (M.A.K.)
| | - Kornelia Krakowska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (J.K.); (M.W.); (M.G.); (K.K.); (P.P.); (A.K.); (H.A.-B.); (J.S.); (M.A.K.)
| | - Paweł Poznański
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (J.K.); (M.W.); (M.G.); (K.K.); (P.P.); (A.K.); (H.A.-B.); (J.S.); (M.A.K.)
| | - Kinga Musiał
- Department of Pediatric Nephrology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland;
| | - Andrzej Konieczny
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (J.K.); (M.W.); (M.G.); (K.K.); (P.P.); (A.K.); (H.A.-B.); (J.S.); (M.A.K.)
| | - Hanna Augustyniak-Bartosik
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (J.K.); (M.W.); (M.G.); (K.K.); (P.P.); (A.K.); (H.A.-B.); (J.S.); (M.A.K.)
| | - Jakub Stojanowski
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (J.K.); (M.W.); (M.G.); (K.K.); (P.P.); (A.K.); (H.A.-B.); (J.S.); (M.A.K.)
| | - Mariusz Andrzej Kusztal
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (J.K.); (M.W.); (M.G.); (K.K.); (P.P.); (A.K.); (H.A.-B.); (J.S.); (M.A.K.)
| | - Tomasz Gołębiowski
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (J.K.); (M.W.); (M.G.); (K.K.); (P.P.); (A.K.); (H.A.-B.); (J.S.); (M.A.K.)
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Moyal A, Nazemian R, Colon EP, Zhu L, Benzar R, Palmer NR, Craycroft M, Hausladen A, Premont RT, Stamler JS, Klick J, Reynolds JD. Renal dysfunction in adults following cardiopulmonary bypass is linked to declines in S-nitroso hemoglobin: a case series. Ann Med Surg (Lond) 2024; 86:2425-2431. [PMID: 38694342 PMCID: PMC11060257 DOI: 10.1097/ms9.0000000000001880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 02/21/2024] [Indexed: 05/04/2024] Open
Abstract
Background Impaired kidney function is frequently observed in patients following cardiopulmonary bypass (CPB). Our group has previously linked blood transfusion to acute declines in S-nitroso haemoglobin (SNO-Hb; the main regulator of tissue oxygen delivery), reductions in intraoperative renal blood flow, and postoperative kidney dysfunction. While not all CPB patients receive blood, kidney injury is still common. We hypothesized that the CPB procedure itself may negatively impact SNO-Hb levels leading to renal dysfunction. Materials and methods After obtaining written informed consent, blood samples were procured immediately before and after CPB, and on postoperative day (POD) 1. SNO-Hb levels, renal function (estimated glomerular filtration rate; eGFR), and plasma erythropoietin (EPO) concentrations were quantified. Additional outcome data were extracted from the patients' medical records. Results Twenty-seven patients were enroled, three withdrew consent, and one was excluded after developing bacteremia. SNO-Hb levels declined after surgery and were directly correlated with declines in eGFR (R=0.48). Conversely, plasma EPO concentrations were elevated and inversely correlated with SNO-Hb (R=-0.53) and eGFR (R=-0.55). Finally, ICU stay negatively correlated with SNO-Hb concentration (R=-0.32). Conclusion SNO-Hb levels are reduced following CPB in the absence of allogenic blood transfusion and are predictive of decreased renal function and prolonged ICU stay. Thus, therapies directed at maintaining or increasing SNO-Hb levels may improve outcomes in adult patients undergoing cardiac surgery.
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Affiliation(s)
| | - Ryan Nazemian
- Institute for Transformative Molecular Medicine
- Departments ofAnesthesiology & Perioperative Medicine
| | - Edwin Pacheco Colon
- Institute for Transformative Molecular Medicine
- Departments ofAnesthesiology & Perioperative Medicine
| | - Lin Zhu
- Institute for Transformative Molecular Medicine
- Departments ofAnesthesiology & Perioperative Medicine
| | - Ruth Benzar
- Institute for Transformative Molecular Medicine
- Departments ofAnesthesiology & Perioperative Medicine
| | | | | | - Alfred Hausladen
- Institute for Transformative Molecular Medicine
- Departments ofAnesthesiology & Perioperative Medicine
| | - Richard T. Premont
- Institute for Transformative Molecular Medicine
- Cardiology, School of Medicine Case Western Reserve University
- Harrington Discovery Institute, University Hospitals-Cleveland Medical Center, Cleveland, OH
| | - Jonathan S. Stamler
- Institute for Transformative Molecular Medicine
- Cardiology, School of Medicine Case Western Reserve University
- Harrington Discovery Institute, University Hospitals-Cleveland Medical Center, Cleveland, OH
| | - John Klick
- Departments ofAnesthesiology & Perioperative Medicine
| | - James D. Reynolds
- Institute for Transformative Molecular Medicine
- Departments ofAnesthesiology & Perioperative Medicine
- Harrington Discovery Institute, University Hospitals-Cleveland Medical Center, Cleveland, OH
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8
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Kjeld T, Krag TO, Brenøe A, Møller AM, Arendrup HC, Højberg J, Fuglø D, Hancke S, Tolbod LP, Gormsen LC, Vissing J, Hansen EG. Hemoglobin concentration and blood shift during dry static apnea in elite breath hold divers. Front Physiol 2024; 15:1305171. [PMID: 38745836 PMCID: PMC11092981 DOI: 10.3389/fphys.2024.1305171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Accepted: 01/23/2024] [Indexed: 05/16/2024] Open
Abstract
Introduction Elite breath-hold divers (BHD) enduring apneas of more than 5 min are characterized by tolerance to arterial blood oxygen levels of 4.3 kPa and low oxygen-consumption in their hearts and skeletal muscles, similar to adult seals. Adult seals possess an adaptive higher hemoglobin-concentration and Bohr effect than pups, and when sedated, adult seals demonstrate a blood shift from the spleen towards the brain, lungs, and heart during apnea. We hypothesized these observations to be similar in human BHD. Therefore, we measured hemoglobin- and 2,3-biphosphoglycerate-concentrations in BHD (n = 11) and matched controls (n = 11) at rest, while myocardial mass, spleen and lower extremity volumes were assessed at rest and during apnea in BHD. Methods and results After 4 min of apnea, left ventricular myocardial mass (LVMM) determined by 15O-H2O-PET/CT (n = 6) and cardiac MRI (n = 6), was unaltered compared to rest. During maximum apnea (∼6 min), lower extremity volume assessed by DXA-scan revealed a ∼268 mL decrease, and spleen volume, assessed by ultrasonography, decreased ∼102 mL. Compared to age, BMI and VO2max matched controls (n = 11), BHD had similar spleen sizes and 2,3- biphosphoglycerate-concentrations, but higher total hemoglobin-concentrations. Conclusion Our results indicate: 1) Apnea training in BHD may increase hemoglobin concentration as an oxygen conserving adaptation similar to adult diving mammals. 2) The blood shift during dry apnea in BHD is 162% more from the lower extremities than from the spleen. 3) In contrast to the previous theory of the blood shift demonstrated in sedated adult seals, blood shift is not towards the heart during dry apnea in humans.
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Affiliation(s)
- Thomas Kjeld
- Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Thomas O. Krag
- Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Anders Brenøe
- Department of Clinical Medicine, Panum Institute, University of Copenhagen, Copenhagen, Denmark
| | - Ann Merete Møller
- Department of Anesthesiology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
| | | | - Jens Højberg
- Department of Cardiothoracic Anesthesiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Dan Fuglø
- Department of Nuclear Medicine, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Søren Hancke
- Department of Clinical Medicine, Panum Institute, University of Copenhagen, Copenhagen, Denmark
| | - Lars Poulsen Tolbod
- Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark
| | - Lars Christian Gormsen
- Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark
| | - John Vissing
- Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Egon Godthaab Hansen
- Department of Anesthesiology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
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9
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Jin X, Zhang Y, Wang D, Zhang X, Li Y, Wang D, Liang Y, Wang J, Zheng L, Song H, Zhu X, Liang J, Ma J, Gao J, Tong J, Shi L. Metabolite and protein shifts in mature erythrocyte under hypoxia. iScience 2024; 27:109315. [PMID: 38487547 PMCID: PMC10937114 DOI: 10.1016/j.isci.2024.109315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/17/2024] Open
Abstract
As the only cell type responsible for oxygen delivery, erythrocytes play a crucial role in supplying oxygen to hypoxic tissues, ensuring their normal functions. Hypoxia commonly occurs under physiological or pathological conditions, and understanding how erythrocytes adapt to hypoxia is fundamental for exploring the mechanisms of hypoxic diseases. Additionally, investigating acute and chronic mountain sickness caused by plateaus, which are naturally hypoxic environments, will aid in the study of hypoxic diseases. In recent years, increasingly developed proteomics and metabolomics technologies have become powerful tools for studying mature enucleated erythrocytes, which has significantly contributed to clarifying how hypoxia affects erythrocytes. The aim of this article is to summarize the composition of the cytoskeleton and cytoplasmic proteins of hypoxia-altered erythrocytes and explore the impact of hypoxia on their essential functions. Furthermore, we discuss the role of microRNAs in the adaptation of erythrocytes to hypoxia, providing new perspectives on hypoxia-related diseases.
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Affiliation(s)
- Xu Jin
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Yingnan Zhang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Ding Wang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Xiaoru Zhang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Yue Li
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Di Wang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Yipeng Liang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Jingwei Wang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Lingyue Zheng
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Haoze Song
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Xu Zhu
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Jing Liang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Jinfa Ma
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Jie Gao
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Jingyuan Tong
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
| | - Lihong Shi
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
- Tianjin Institutes of Health Science, Tianjin 301600, China
- CAMS Center for Stem Cell Medicine, PUMC Department of Stem Cell and Regenerative Medicine, Tianjin 300020, China
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10
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Zhou X, He K, Zhao J, Wei G, You Q, Du H, Gu W, Niu H, Jin Q, Wang J, Tang F. Use of Transcriptome Sequencing to Analyze the Effects of Different Doses of an Astragalus-Rhubarb-Saffron Mixture in Mice with Diabetic Kidney Disease. Diabetes Metab Syndr Obes 2024; 17:1795-1808. [PMID: 38655491 PMCID: PMC11036333 DOI: 10.2147/dmso.s449792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 04/08/2024] [Indexed: 04/26/2024] Open
Abstract
Purpose To investigate the therapeutic effect and underlying mechanism of a traditional Chinese medicine (TCM) mixture consisting of Astragalus, rhubarb, and saffron in a mouse model of diabetic kidney disease (DKD). Methods Forty-eight db/db mice received no TCM (DKD model), low-dose TCM, medium-dose TCM, or high-dose TCM, and an additional 12 db/m mice received no TCM (normal control). Intragastric TCM or saline (controls) was administered daily for 24 weeks. Blood glucose, body weight, serum creatinine (SCr), blood urea nitrogen (BUN), blood lipids, and urinary microalbumin were measured every four weeks, and the urinary albumin excretion rate (UAER) was calculated. After 24 weeks, kidney tissues were collected for transcriptome sequencing, and the main functions of these genes were determined via functional enrichment analysis. Results Compared with the DKD model group, the medium-dose and high-dose TCM groups had significantly decreased levels of SCr, BUN, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and UAER (all p<0.05). We identified 42 genes that potentially functioned in this therapeutic response, and the greatest effect on gene expression was in the high-dose TCM group. We also performed functional enrichment analysis to explore the potential mechanisms of action of these different genes. Conclusion A high-dose of the Astragalus-rhubarb-saffron TCM provided the best prevention of DKD. Analysis of the kidney transcriptome suggested that this TCM mixture may prevent DKD by altering immune responses and oxygen delivery by hemoglobin.
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Affiliation(s)
- Xiaochun Zhou
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
- Department of Cardiovascular Disease, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
- Department of Nephrology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
| | - Kaiying He
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
- Department of Nephrology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
| | - Jing Zhao
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
- Department of Nephrology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
| | - Guohua Wei
- Department of Nephrology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
| | - Qicai You
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
- Department of Nephrology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
| | - Hongxuan Du
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
- Department of Nephrology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
| | - Wenjiao Gu
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
- Department of Cardiovascular Disease, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
| | - Haiyu Niu
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
- Department of Tumor, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
| | - Qiaoying Jin
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
- Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
| | - Jianqin Wang
- Department of Nephrology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
| | - Futian Tang
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
- Department of Cardiovascular Disease, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China
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11
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Umer EK, Abebe AT, Kebede YT, Bekele NT. Burden and risk profile of acute kidney injury in severe COVID-19 pneumonia admissions: a Finding from Jimma University medical center, Ethiopia. BMC Nephrol 2024; 25:109. [PMID: 38504176 PMCID: PMC10953204 DOI: 10.1186/s12882-024-03522-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 02/25/2024] [Indexed: 03/21/2024] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is a serious complication of the Corona Virus Disease of 2019 (COVID-19). However, data on its magnitude and risk factors among hospitalized patients in Ethiopia is limited. This study aimed to determine the magnitude of AKI and associated factors among patients admitted for severe COVID-19 pneumonia. METHODS An institution-based retrospective cross-sectional study was conducted among 224 patients admitted to Jimma University Medical Center in Ethiopia for severe COVID-19 pneumonia from May 2020 to December 2021. Systematic random sampling was used to select study participants. Medical records were reviewed to extract sociodemographic, clinical, laboratory, therapeutic, and comorbidity data. Bivariable and multivariable logistic regressions were performed to examine factors associated with AKI. The magnitude of the association between the explanatory variables and AKI was estimated using an adjusted odds ratio (AOR) with a 95% confidence interval (CI), and significance was declared at a p-value of 0.05. RESULTS The magnitude of AKI was 42% (95% CI: 35.3-48.2%) in the study area. Mechanical ventilation, vasopressors, and antibiotics were required in 32.6, 3.7, and 97.7% of the patients, respectively. After adjusting for possible confounders, male sex (AOR 2.79, 95% CI: 1.3-6.5), fever (AOR 6.5, 95% CI: 2.7-15.6), hypoxemia (AOR 5.1, 95% CI: 1.4-18.9), comorbidities (AOR 2.8, 95% CI: 1.1-7.0), and severe anemia (AOR 10, 95% CI: 1.7-65.7) remained significantly associated with higher odds of AKI. CONCLUSION The burden of AKI among patients with severe COVID-19 pneumonia is high in our setting. Male sex, abnormal vital signs, chronic conditions, and anemia can identify individuals at increased risk and require close monitoring and prevention efforts.
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Affiliation(s)
- Ebrahim Kelil Umer
- Department of Internal Medicine, Adama Hospital Medical College, Adama, Ethiopia
| | - Abel Tezera Abebe
- School of Medicine, Faculty of Medical Sciences, Institute of Health, Jimma University, Jimma, Ethiopia.
| | - Yabets Tesfaye Kebede
- School of Medicine, Faculty of Medical Sciences, Institute of Health, Jimma University, Jimma, Ethiopia
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12
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Randle RK, Amara VR, Popik W. IFI16 Is Indispensable for Promoting HIF-1α-Mediated APOL1 Expression in Human Podocytes under Hypoxic Conditions. Int J Mol Sci 2024; 25:3324. [PMID: 38542298 PMCID: PMC10970439 DOI: 10.3390/ijms25063324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 02/28/2024] [Accepted: 03/13/2024] [Indexed: 04/04/2024] Open
Abstract
Genetic variants in the protein-coding regions of APOL1 are associated with an increased risk and progression of chronic kidney disease (CKD) in African Americans. Hypoxia exacerbates CKD progression by stabilizing HIF-1α, which induces APOL1 transcription in kidney podocytes. However, the contribution of additional mediators to regulating APOL1 expression under hypoxia in podocytes is unknown. Here, we report that a transient accumulation of HIF-1α in hypoxia is sufficient to upregulate APOL1 expression in podocytes through a cGAS/STING/IRF3-independent pathway. Notably, IFI16 ablation impedes hypoxia-driven APOL1 expression despite the nuclear accumulation of HIF-1α. Co-immunoprecipitation assays indicate no direct interaction between IFI16 and HIF-1α. Our studies identify hypoxia response elements (HREs) in the APOL1 gene enhancer/promoter region, showing increased HIF-1α binding to HREs located in the APOL1 gene enhancer. Luciferase reporter assays confirm the role of these HREs in transcriptional activation. Chromatin immunoprecipitation (ChIP)-qPCR assays demonstrate that IFI16 is not recruited to HREs, and IFI16 deletion reduces HIF-1α binding to APOL1 HREs. RT-qPCR analysis indicates that IFI16 selectively affects APOL1 expression, with a negligible impact on other hypoxia-responsive genes in podocytes. These findings highlight the unique contribution of IFI16 to hypoxia-driven APOL1 gene expression and suggest alternative IFI16-dependent mechanisms regulating APOL1 gene expression under hypoxic conditions.
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Affiliation(s)
- Richaundra K. Randle
- Department of Biomedical Sciences, School of Graduate Studies, Meharry Medical College, Nashville, TN 37208, USA;
- Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, TN 37208, USA;
| | - Venkateswara Rao Amara
- Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, TN 37208, USA;
- Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research, Hajipur 844102, Bihar, India
| | - Waldemar Popik
- Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, TN 37208, USA;
- Department of Internal Medicine, School of Medicine, Meharry Medical College, Nashville, TN 37208, USA
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13
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Chae SY, Kim Y, Park CW. Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia. Antioxidants (Basel) 2023; 12:2083. [PMID: 38136203 PMCID: PMC10740440 DOI: 10.3390/antiox12122083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 11/26/2023] [Accepted: 12/01/2023] [Indexed: 12/24/2023] Open
Abstract
Oxidative stress, a hallmark pathophysiological feature in diabetic kidney disease (DKD), arises from the intricate interplay between pro-oxidants and anti-oxidants. While hyperglycemia has been well established as a key contributor, lipotoxicity emerges as a significant instigator of oxidative stress. Lipotoxicity encompasses the accumulation of lipid intermediates, culminating in cellular dysfunction and cell death. However, the mechanisms underlying lipotoxic kidney injury in DKD still require further investigation. The key role of cell metabolism in the maintenance of cell viability and integrity in the kidney is of paramount importance to maintain proper renal function. Recently, dysfunction in energy metabolism, resulting from an imbalance in oxygen levels in the diabetic condition, may be the primary pathophysiologic pathway driving DKD. Therefore, we aim to shed light on the pivotal role of oxidative stress related to lipotoxicity and renal hypoxia in the initiation and progression of DKD. Multifaceted mechanisms underlying lipotoxicity, including oxidative stress with mitochondrial dysfunction, endoplasmic reticulum stress activated by the unfolded protein response pathway, pro-inflammation, and impaired autophagy, are delineated here. Also, we explore potential therapeutic interventions for DKD, targeting lipotoxicity- and hypoxia-induced oxidative stress. These interventions focus on ameliorating the molecular pathways of lipid accumulation within the kidney and enhancing renal metabolism in the face of lipid overload or ameliorating subsequent oxidative stress. This review highlights the significance of lipotoxicity, renal hypoxia-induced oxidative stress, and its potential for therapeutic intervention in DKD.
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Affiliation(s)
- Seung Yun Chae
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea; (S.Y.C.); (Y.K.)
| | - Yaeni Kim
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea; (S.Y.C.); (Y.K.)
| | - Cheol Whee Park
- Division of Nephrology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea; (S.Y.C.); (Y.K.)
- Institute for Aging and Metabolic Disease, Seoul St. Mary’s Hospital, The College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea
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14
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Zhou D, Li D, Nie H, Duan J, Liu S, Wang Y, Zuo W. Generation of renal tubular organoids from adult SOX9 + kidney progenitor cells. LIFE MEDICINE 2023; 2:lnad047. [PMID: 39872058 PMCID: PMC11749593 DOI: 10.1093/lifemedi/lnad047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Accepted: 11/22/2023] [Indexed: 01/29/2025]
Abstract
The pathogenesis of several kidney diseases results in the eventual destruction of the renal tubular system, which can progress to end-stage renal disease. Previous studies have demonstrated the involvement of a population of SOX9-positive cells in kidney regeneration and repair process following kidney injury. However, the ability of these cells to autonomously generate kidney organoids has never been investigated. Here, we isolated SOX9+ kidney progenitor cells (KPCs) from both mice and humans and tested their differentiation potential in vitro. The data showed that the human SOX9+ KPC could self-assemble into organoids with kidney-like morphology. We also used single-cell RNA sequencing to characterize the organoid cell populations and identified four distinct types of renal tubular cells. Compared to the induced pluripotent stem cell-derived kidney organoids, KPC demonstrated more tubular differentiation potential but failed to differentiate into glomerular cells. KPC-derived organoid formation involved the expression of genes related to metanephric development and followed a similar mechanism to renal injury repair in acute kidney injury patients. Altogether, our study provided a potentially useful approach to generating kidney tubular organoids for future application.
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Affiliation(s)
- Dewei Zhou
- Laboratory of Transplant Engineering and Transplant Immunology, West China Hospital, Sichuan University, Chengdu 610041, China
- Department of Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Dandan Li
- Department of Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Hao Nie
- Department of Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Jun Duan
- Department of Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
| | - Sarah Liu
- Super Organ R&D Center, Regend Therapeutics, Shanghai 201210, China
| | - Yujia Wang
- Department of Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
- Super Organ R&D Center, Regend Therapeutics, Shanghai 201210, China
| | - Wei Zuo
- Laboratory of Transplant Engineering and Transplant Immunology, West China Hospital, Sichuan University, Chengdu 610041, China
- Department of Regenerative Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
- Super Organ R&D Center, Regend Therapeutics, Shanghai 201210, China
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15
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Tanzadehpanah H, Lotfian E, Avan A, Saki S, Nobari S, Mahmoodian R, Sheykhhasan M, Froutagh MHS, Ghotbani F, Jamshidi R, Mahaki H. Role of SARS-COV-2 and ACE2 in the pathophysiology of peripheral vascular diseases. Biomed Pharmacother 2023; 166:115321. [PMID: 37597321 DOI: 10.1016/j.biopha.2023.115321] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 08/08/2023] [Accepted: 08/10/2023] [Indexed: 08/21/2023] Open
Abstract
The occurrence of a novel coronavirus known as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), created a serious challenge worldwide. SARS-CoV-2 has high infectivity, the ability to be transmitted even during the asymptomatic phase, and relatively low virulence, which has resulted in rapid transmission. SARS-CoV-2 can invade epithelial cells, hence, many patients infected with SARS-CoV-2 have suffered from vascular diseases (VDs) in addition to pulmonary manifestations. Accordingly, SARS-CoV-2 may can worsen the clinical condition of the patients with pre-existing VDs. Endothelial cells express angiotensin-converting enzyme 2 (ACE2). ACE2 is a biological enzyme that converts angiotensin (Ang)- 2 to Ang-(1-7). SARS-CoV-2 uses ACE2 as a cell receptor for viral entry. Thus, the SARS-CoV-2 virus promotes downregulation of ACE2, Ang-(1-7), and anti-inflammatory cytokines, as well as, an increase in Ang-2, resulting in pro-inflammatory cytokines. SARS-CoV-2 infection can cause hypertension, and endothelial damage, which can lead to intravascular thrombosis. In this review, we have concentrated on the effect of SARS-CoV-2 in peripheral vascular diseases (PVDs) and ACE2 as an enzyme in Renin-angiotensin aldosterone system (RAAS). A comprehensive search was performed on PubMed, Google Scholar, Scopus, using related keywords. Articles focusing on ("SARS-CoV-2", OR "COVID-19"), AND ("Vascular disease", OR "Peripheral vascular disease", OR interested disease name) with regard to MeSH terms, were selected. According to the studies, it is supposed that vascular diseases may increase susceptibility to severe SARS-CoV-2 infection due to increased thrombotic burden and endothelial dysfunction. Understanding SARS-CoV-2 infection mechanism and vascular system pathogenesis is crucial for effective management and treatment in pre-existing vascular diseases.
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Affiliation(s)
- Hamid Tanzadehpanah
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences; Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Elham Lotfian
- Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Avan
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences; Medical Genetics Research Center, Mashhad University of Medical Sciences; Medical Genetics Research center, Mashhad University of Medical Sciences; Basic Sciences Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sahar Saki
- Molecular Medicine Research Center, Hamadan University of Medical Science, Hamadan Iran
| | - Sima Nobari
- Molecular Medicine Research Center, Hamadan University of Medical Science, Hamadan Iran
| | - Roghaye Mahmoodian
- Molecular Medicine Research Center, Hamadan University of Medical Science, Hamadan Iran
| | - Mohsen Sheykhhasan
- Department of Mesenchymal Stem Cells, Academic Center for Education, Culture and Research, Qom, Iran
| | | | - Farzaneh Ghotbani
- Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran
| | - Raoufeh Jamshidi
- Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran
| | - Hanie Mahaki
- Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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16
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Habas E, Al Adab A, Arryes M, Alfitori G, Farfar K, Habas AM, Akbar RA, Rayani A, Habas E, Elzouki A. Anemia and Hypoxia Impact on Chronic Kidney Disease Onset and Progression: Review and Updates. Cureus 2023; 15:e46737. [PMID: 38022248 PMCID: PMC10631488 DOI: 10.7759/cureus.46737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/09/2023] [Indexed: 12/01/2023] Open
Abstract
Chronic kidney disease (CKD) is caused by hypoxia in the renal tissue, leading to inflammation and increased migration of pathogenic cells. Studies showed that leukocytes directly sense hypoxia and respond by initiating gene transcription, encoding the 2-integrin adhesion molecules. Moreover, other mechanisms participate in hypoxia, including anemia. CKD-associated anemia is common, which induces and worsens hypoxia, contributing to CKD progression. Anemia correction can slow CKD progression, but it should be cautiously approached. In this comprehensive review, the underlying pathophysiology mechanisms and the impact of renal tissue hypoxia and anemia in CKD onset and progression will be reviewed and discussed in detail. Searching for the latest updates in PubMed Central, Medline, PubMed database, Google Scholar, and Google search engines were conducted for original studies, including cross-sectional studies, cohort studies, clinical trials, and review articles using different keywords, phrases, and texts such as "CKD progression, anemia in CKD, CKD, anemia effect on CKD progression, anemia effect on CKD progression, and hypoxia and CKD progression". Kidney tissue hypoxia and anemia have an impact on CKD onset and progression. Hypoxia causes nephron cell death, enhancing fibrosis by increasing interstitium protein deposition, inflammatory cell activation, and apoptosis. Severe anemia correction improves life quality and may delay CKD progression. Detection and avoidance of the risk factors of hypoxia prevent recurrent acute kidney injury (AKI) and reduce the CKD rate. A better understanding of kidney hypoxia would prevent AKI and CKD and lead to new therapeutic strategies.
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Affiliation(s)
| | - Aisha Al Adab
- Internal Medicine, Hamad General Hospital, Doha, QAT
| | - Mehdi Arryes
- Internal Medicine, Hamad General Hospital, Doha, QAT
| | | | | | - Ala M Habas
- Internal Medicine, Tripoli University, Tripoli, LBY
| | - Raza A Akbar
- Internal Medicine, Hamad General Hospital, Doha, QAT
| | - Amnna Rayani
- Hemat-oncology Department, Pediatric Tripoli Hospital, Tripoli University, Tripoli, LBY
| | - Eshrak Habas
- Internal Medicine, Tripoli University, Tripoli, LBY
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Danilova EY, Maslova AO, Stavrianidi AN, Nosyrev AE, Maltseva LD, Morozova OL. CKD Urine Metabolomics: Modern Concepts and Approaches. PATHOPHYSIOLOGY 2023; 30:443-466. [PMID: 37873853 PMCID: PMC10594523 DOI: 10.3390/pathophysiology30040033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/31/2023] [Accepted: 09/05/2023] [Indexed: 10/25/2023] Open
Abstract
One of the primary challenges regarding chronic kidney disease (CKD) diagnosis is the absence of reliable methods to detect early-stage kidney damage. A metabolomic approach is expected to broaden the current diagnostic modalities by enabling timely detection and making the prognosis more accurate. Analysis performed on urine has several advantages, such as the ease of collection using noninvasive methods and its lower protein and lipid content compared with other bodily fluids. This review highlights current trends in applied analytical methods, major discoveries concerning pathways, and investigated populations in the context of urine metabolomic research for CKD over the past five years. Also, we are presenting approaches, instrument upgrades, and sample preparation modifications that have improved the analytical parameters of methods. The onset of CKD leads to alterations in metabolism that are apparent in the molecular composition of urine. Recent works highlight the prevalence of alterations in the metabolic pathways related to the tricarboxylic acid cycle and amino acids. Including diverse patient cohorts, using numerous analytical techniques with modifications and the appropriate annotation and explanation of the discovered biomarkers will help develop effective diagnostic models for different subtypes of renal injury with clinical applications.
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Affiliation(s)
- Elena Y. Danilova
- Molecular Theranostics Institute, Biomedical Science and Technology Park, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8 Trubetskaya ul, 119991 Moscow, Russia (A.E.N.)
- Department of Chemistry, M.V. Lomonosov Moscow State University, 1 Leninskiye Gory Str., 119991 Moscow, Russia
| | - Anna O. Maslova
- Molecular Theranostics Institute, Biomedical Science and Technology Park, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8 Trubetskaya ul, 119991 Moscow, Russia (A.E.N.)
| | - Andrey N. Stavrianidi
- Department of Chemistry, M.V. Lomonosov Moscow State University, 1 Leninskiye Gory Str., 119991 Moscow, Russia
| | - Alexander E. Nosyrev
- Molecular Theranostics Institute, Biomedical Science and Technology Park, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8 Trubetskaya ul, 119991 Moscow, Russia (A.E.N.)
| | - Larisa D. Maltseva
- Department of Pathophysiology, Institute of Biodesign and Modeling of Complex System, I.M. Sechenov First Moscow State Medical University (Sechenov University), 13-1 Nikitsky Boulevard, 119019 Moscow, Russia; (L.D.M.)
| | - Olga L. Morozova
- Department of Pathophysiology, Institute of Biodesign and Modeling of Complex System, I.M. Sechenov First Moscow State Medical University (Sechenov University), 13-1 Nikitsky Boulevard, 119019 Moscow, Russia; (L.D.M.)
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18
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Wei JY, Hu MY, Chen XQ, Wei JS, Chen J, Qin XK, Lei FY, Zou JS, Zhu SQ, Qin YH. Hypobaric Hypoxia Aggravates Renal Injury by Inducing the Formation of Neutrophil Extracellular Traps through the NF-κB Signaling Pathway. Curr Med Sci 2023:10.1007/s11596-023-2744-3. [PMID: 37264195 DOI: 10.1007/s11596-023-2744-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 11/24/2022] [Indexed: 06/03/2023]
Abstract
OBJECTIVE The hypersensitivity of the kidney makes it susceptible to hypoxia injury. The involvement of neutrophil extracellular traps (NETs) in renal injury resulting from hypobaric hypoxia (HH) has not been reported. In this study, we aimed to investigate the expression of NETs in renal injury induced by HH and the possible underlying mechanism. METHODS A total of 24 SD male rats were divided into three groups (n=8 each): normal control group, hypoxia group and hypoxia+pyrrolidine dithiocarbamate (PDTC) group. Rats in hypoxia group and hypoxia+PDTC group were placed in animal chambers with HH which was caused by simulating the altitude at 7000 meters (oxygen partial pressure about 6.9 kPa) for 7 days. PDTC was administered at a dose of 100 mg/kg intraperitoneally once daily for 7 days. Pathological changes of the rat renal tissues were observed under a light microscope; the levels of serum creatinine (SCr), blood urea nitrogen (BUN), cell-free DNA (cf-DNA) and reactive oxygen species (ROS) were measured; the expression levels of myeloperoxidase (MPO), citrullinated histone H3 (cit-H3), B-cell lymphoma 2 (Bcl-2), Bax, nuclear factor kappa B (NF-κB) p65 and phospho-NF-κB p65 (p-NF-κB p65) in rat renal tissues were detected by qRT-qPCR and Western blotting; the localization of NF-κB p65 expression in rat renal tissues was observed by immunofluorescence staining and the expression changes of NETs in rat renal tissues were detected by multiplex fluorescence immunohistochemical staining. RESULTS After hypoxia, the expression of NF-κB protein in renal tissues was significantly increased, the levels of SCr, BUN, cf-DNA and ROS in serum were significantly increased, the formation of NETs in renal tissues was significantly increased, and a large number of tubular dilatation and lymphocyte infiltration were observed in renal tissues. When PDTC was used to inhibit NF-κB activation, NETs formation in renal tissue was significantly decreased, the expression level of Bcl-2 in renal tissues was significantly increased, the expression level of Bax was significantly decreased, and renal injury was significantly alleviated. CONCLUSION HH induces the formation of NETs through the NF-κB signaling pathway, and it promotes apoptosis and aggravates renal injury by decreasing Bcl-2 and increasing Bax expression.
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Affiliation(s)
- Jun-Yu Wei
- Department of Pediatrics, the First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, China
| | - Miao-Yue Hu
- Department of Pediatrics, the First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, China
| | - Xiu-Qi Chen
- Department of Pediatrics, the First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, China
| | - Jin-Shuang Wei
- Department of Pediatrics, the First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, China
| | - Jie Chen
- Department of Pediatrics, the First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, China
| | - Xuan-Kai Qin
- Department of Pediatrics, the First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, China
| | - Feng-Ying Lei
- Department of Pediatrics, the First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, China
| | - Jia-Sen Zou
- Children's Hospital of Chongqing Medical University, Chongqing, 400015, China
| | - Shi-Qun Zhu
- Shenzhen Children's Hospital, Shenzhen, 518034, China
| | - Yuan-Han Qin
- Department of Pediatrics, the First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, China.
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19
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Chu YT, Chen BH, Chen HH, Lee JC, Kuo TJ, Chiu HC, Lu WH. Hypoxia-Induced Kidney Injury in Newborn Rats. TOXICS 2023; 11:260. [PMID: 36977025 PMCID: PMC10053593 DOI: 10.3390/toxics11030260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/08/2023] [Accepted: 03/10/2023] [Indexed: 06/18/2023]
Abstract
Exposure to hypoxia during the early postnatal period can have adverse effects on vital organs. Neonatal Sprague-Dawley rats housed in a hypoxic chamber were compared to those in a normoxic chamber from postnatal days 0 to 7. Arterial blood was collected to evaluate renal function and hypoxia. Kidney morphology and fibrosis were evaluated using staining methods and immunoblotting. In the kidneys of the hypoxic group, protein expressions of hypoxia-inducible factor-1 were higher than those in the normoxic group. Hypoxic rats had higher levels of hematocrit, serum creatinine, and lactate than normoxic rats. Body weight was reduced, and protein loss of kidney tissue was observed in hypoxic rats compared to normoxic rats. Histologically, hypoxic rats showed glomerular atrophy and tubular injury. Renal fibrosis with collagen fiber deposition was observed in the hypoxic group. The expression of nicotinamide adenine dinucleotide phosphate oxidases was enhanced in the kidneys of hypoxic rats. Proteins involved in apoptosis were upregulated in the kidneys of hypoxic rats. An increase in the expression of pro-inflammatory cytokines was also observed in the kidneys of hypoxic rats. Hypoxic kidney injury in neonatal rats was associated with oxidative stress, inflammation, apoptosis, and fibrosis.
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Affiliation(s)
- Yi-Ting Chu
- Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan
| | - Bo-Hau Chen
- Department of Pediatrics, Taoyuan Armed Forces General Hospital, Taoyuan 32551, Taiwan
| | - Hsin-Hung Chen
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan
| | - Jui-Chen Lee
- Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan
| | - Tzu-Jiun Kuo
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan
| | - Hsiang-Chin Chiu
- Department of Pediatrics, Pingtung Veterans General Hospital, Pingtung 91245, Taiwan
| | - Wen-Hsien Lu
- Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung 813414, Taiwan
- School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804201, Taiwan
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20
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Appleby RB, Vaden SL, Monteith G, Seiler GS. Shear wave elastography evaluation of cats with chronic kidney disease. Vet Radiol Ultrasound 2023; 64:330-336. [PMID: 36324225 DOI: 10.1111/vru.13184] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 09/16/2022] [Accepted: 09/17/2022] [Indexed: 11/06/2022] Open
Abstract
Chronic kidney disease (CKD) is a major health condition in cats that can lead to poor quality of life and financial implications for therapy. Currently staging and identification of CKD is limited by diagnostic testing such as creatinine and urine-specific gravity, which do not change until late in the disease course. Other methods to evaluate CKD would be valuable in the clinical setting. Shear wave elastography is one novel ultrasound method, which has shown promise in identifying increases in tissue stiffness and identifying CKD in people. As CKD is often histologically characterized by tubulointerstitial fibrosis, shear wave elastography has the potential to identify CKD and differentiate between stages of CKD in cats. This prospective observational case-control study with 78 cats found no difference in shear wave velocities between groups (P = 0.33), a contradictory finding to one prior publication. There was no effect of weight (P = 0.65), nor the presence of mineralization (P = 0.31) or infarction (P = 0.52) on cortical shear wave velocities. There was a significant effect of age on shear wave velocity (P = 0.018) where velocities increased with age. The intraclass correlation coefficient was only moderate (0.62). Possible reasons for the difference in results between our work and that published prior, include differences in methodology and differences in instrumentation. Variability in measurements in our population may be due to the effects of respiratory motion or limitations in shear wave elastography software. As such, shear wave elastography is not currently recommended as a tool to evaluate CKD in cats and further work is necessary.
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Affiliation(s)
- Ryan B Appleby
- Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Canada
| | - Shelly L Vaden
- Department of Clinical Sciences, NC State College of Veterinary Medicine, Raleigh, North Carolina, USA
| | - Gabrielle Monteith
- Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Canada
| | - Gabriela S Seiler
- Department of Molecular and Biological Sciences, NC State College of Veterinary Medicine, Raleigh, North Carolina, USA
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21
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Zou Q, Lai Y, Lun ZR. Exploring the Association between Oxygen Concentration and Life Expectancy in China: A Quantitative Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:1125. [PMID: 36673882 PMCID: PMC9859324 DOI: 10.3390/ijerph20021125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 12/29/2022] [Accepted: 01/06/2023] [Indexed: 06/17/2023]
Abstract
The aim of this study was to investigate and quantify the association between oxygen concentration and life expectancy. The data from 34 provinces and 39 municipalities were included in all analyses. Bayesian regression modeling with spatial-specific random effects was used to quantify the impact of oxygen concentration (measured as partial pressure of oxygen) on life expectancy, adjusting for other potential confounding factors. We used hierarchical cluster analysis to group the provinces according to disease burden and analyzed the oxygen levels and the characteristics of causes of death between the clusters. The Bayesian regression analysis showed that the life expectancy at the provincial level increased by 0.15 (95% CI: 0.10-0.19) years, while at the municipal level, it increased by 0.17 (95% CI: 0.12-0.22) years, with each additional unit (mmHg) of oxygen concentration, after controlling for potential confounding factors. Three clusters were identified in the hierarchical cluster analysis, which were characterized by different oxygen concentrations, and the years of life lost from causes potentially related to hypoxia were statistically significantly different between the clusters. A positive correlation was found between oxygen concentration and life expectancy in China. The differences in causes of death and oxygen levels in the provincial clusters suggested that oxygen concentration may be an important factor in life expectancy when mediated by diseases that are potentially related to hypoxia.
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Affiliation(s)
- Qing Zou
- Department of Medical Statistics, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China
| | - Yingsi Lai
- Department of Medical Statistics, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China
- Sun Yat-Sen Global Health Institute, Sun Yat-Sen University, Guangzhou 510080, China
| | - Zhao-Rong Lun
- State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China
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22
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Ivnitsky JJ, Schäfer TV, Rejniuk VL, Golovko AI. Endogenous humoral determinants of vascular endothelial dysfunction as triggers of acute poisoning complications. J Appl Toxicol 2023; 43:47-65. [PMID: 35258106 DOI: 10.1002/jat.4312] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/13/2022] [Accepted: 02/26/2022] [Indexed: 12/16/2022]
Abstract
The vascular endothelium is not only the semipermeable membrane that separates tissue from blood but also an organ that regulates inflammation, vascular tone, blood clotting, angiogenesis and synthesis of connective tissue proteins. It is susceptible to the direct cytotoxic action of numerous xenobiotics and to the acute hypoxia that accompanies acute poisoning. This damage is superimposed on the preformed state of the vascular endothelium, which, in turn, depends on many humoral factors. The probability that an exogenous toxicant will cause life-threatening dysfunction of the vascular endothelium, thereby complicating the course of acute poisoning, increases with an increase in the content of endogenous substances in the blood that disrupt endothelial function. These include ammonia, bacterial endotoxin, indoxyl sulfate, para-cresyl sulfate, trimethylamine N-oxide, asymmetric dimethylarginine, glucose, homocysteine, low-density and very-low-density lipoproteins, free fatty acids and products of intravascular haemolysis. Some other endogenous substances (albumin, haptoglobin, haemopexin, biliverdin, bilirubin, tetrahydrobiopterin) or food-derived compounds (ascorbic acid, rutin, omega-3 polyunsaturated fatty acids, etc.) reduce the risk of lethal vascular endothelial dysfunction. The individual variability of the content of these substances in the blood contributes to the stochasticity of the complications of acute poisoning and is a promising target for the risk reduction measures. Another feasible option may be the repositioning of drugs that affect the function of the vascular endothelium while being currently used for other indications.
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Affiliation(s)
- Jury Ju Ivnitsky
- Golikov Research Clinical Center of Toxicology under the Federal Medical Biological Agency, Saint Petersburg, Russia
| | - Timur V Schäfer
- State Scientific Research Test Institute of the Military Medicine of Defense Ministry of the Russian Federation, Saint Petersburg, Russia
| | - Vladimir L Rejniuk
- Golikov Research Clinical Center of Toxicology under the Federal Medical Biological Agency, Saint Petersburg, Russia
| | - Alexandr I Golovko
- Golikov Research Clinical Center of Toxicology under the Federal Medical Biological Agency, Saint Petersburg, Russia
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23
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Nie Y, Wang L, You X, Wang X, Wu J, Zheng Z. Low dimensional nanomaterials for treating acute kidney injury. J Nanobiotechnology 2022; 20:505. [PMID: 36456976 PMCID: PMC9714216 DOI: 10.1186/s12951-022-01712-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 11/15/2022] [Indexed: 12/02/2022] Open
Abstract
Acute kidney injury (AKI) is one of the most common severe complications among hospitalized patients. In the absence of specific drugs to treat AKI, hemodialysis remains the primary clinical treatment for AKI patients. AKI treatment has received significant attention recently due to the excellent drug delivery capabilities of low-dimensional nanomaterials (LDNs) and their unique therapeutic effects. Diverse LDNs have been proposed to treat AKI, with promising results and the potential for future clinical application. This article aims to provide an overview of the pathogenesis of AKI and the recent advances in the treatment of AKI using different types of LDNs. In addition, it is intended to provide theoretical support for the design of LDNs and implications for AKI treatment.
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Affiliation(s)
- Yuanpeng Nie
- Department of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China
| | - Liying Wang
- Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China
| | - Xinru You
- Department of Pediatrics, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China
| | - Xiaohua Wang
- Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Nansha, Guangzhou, 511400, China
| | - Jun Wu
- Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.
- Bioscience and Biomedical Engineering Thrust, The Hong Kong University of Science and Technology (Guangzhou), Nansha, Guangzhou, 511400, China.
- Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong SAR, China.
| | - Zhihua Zheng
- Department of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, China.
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24
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Renal Fibrosis in Lupus Nephritis. Int J Mol Sci 2022; 23:ijms232214317. [PMID: 36430794 PMCID: PMC9699516 DOI: 10.3390/ijms232214317] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/14/2022] [Accepted: 11/16/2022] [Indexed: 11/19/2022] Open
Abstract
Fibrosis can be defined as a pathological process in which deposition of connective tissue replaces normal parenchyma. The kidney, like any organ or tissue, can be impacted by this maladaptive reaction, resulting in persistent inflammation or long-lasting injury. While glomerular injury has traditionally been regarded as the primary focus for classification and prognosis of lupus nephritis (LN), increasing attention has been placed on interstitial fibrosis and tubular atrophy as markers of injury severity, predictors of therapeutic response, and prognostic factors of renal outcome in recent years. This review will discuss the fibrogenesis in LN and known mechanisms of renal fibrosis. The importance of the chronicity index, which was recently added to the histological categorization of LN, and its role in predicting treatment response and renal prognosis for patients with LN, will be explored. A better understanding of cellular and molecular pathways involved in fibrosis in LN could enable the identification of individuals at higher risk of progression to chronic kidney disease and end-stage renal disease, and the development of new therapeutic strategies for lupus patients.
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25
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Metabolic signatures of immune cells in chronic kidney disease. Expert Rev Mol Med 2022; 24:e40. [PMID: 36268748 PMCID: PMC9884772 DOI: 10.1017/erm.2022.35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Immune cells play a key role in maintaining renal dynamic balance and dealing with renal injury. The physiological and pathological functions of immune cells are intricately connected to their metabolic characteristics. However, immunometabolism in chronic kidney disease (CKD) is not fully understood. Pathophysiologically, disruption of kidney immune cells homeostasis causes inflammation and tissue damage via triggering metabolic reprogramming. The diverse metabolic characteristics of immune cells at different stages of CKD are strongly associated with their different pathological effect. In this work, we reviewed the metabolic characteristics of immune cells (macrophages, natural killer cells, T cells, natural killer T cells and B cells) and several non-immune cells, as well as potential treatments targeting immunometabolism in CKD. We attempt to elaborate on the metabolic signatures of immune cells and their intimate correlation with non-immune cells in CKD.
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26
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Wang SY, Gao J, Zhao JH. Effects of high altitude on renal physiology and kidney diseases. Front Physiol 2022; 13:969456. [PMID: 36338473 PMCID: PMC9630589 DOI: 10.3389/fphys.2022.969456] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 10/10/2022] [Indexed: 11/13/2022] Open
Abstract
The hypobaric and hypoxic conditions of high-altitude areas exert adverse effects on the respiratory, circulatory and nervous systems. The kidneys have an abundant blood supply (20%–25% of cardiac output) and high blood flow; thus, they are susceptible to the effects of hypoxia. However, the effects of acute and chronic exposure to high altitudes on renal physiology and pathology are not fully understood. Moreover, few studies have investigated the impact of high-altitude exposure on patients with chronic kidney disease or acute kidney injury. In this review, we summarized changes in renal physiology and renal pathology due to high-altitude exposure as well as the impact of high-altitude exposure on existing kidney diseases, with the aim of informing the prevention and treatment of kidney diseases at high altitudes.
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Affiliation(s)
- Si-Yang Wang
- 953th Hospital, Shigatse Branch, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Jie Gao
- Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Jing-Hong Zhao
- Department of Nephrology, The Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- *Correspondence: Jing-Hong Zhao,
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27
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Hypoxia-Inducible Factors and Diabetic Kidney Disease—How Deep Can We Go? Int J Mol Sci 2022; 23:ijms231810413. [PMID: 36142323 PMCID: PMC9499602 DOI: 10.3390/ijms231810413] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/29/2022] [Accepted: 08/31/2022] [Indexed: 11/17/2022] Open
Abstract
Diabetes is one of the leading causes of chronic kidney disease (CKD), and multiple underlying mechanisms involved in pathogenesis of diabetic nephropathy (DN) have been described. Although various treatments and diagnosis applications are available, DN remains a clinical and economic burden, considering that about 40% of type 2 diabetes patients will develop nephropathy. In the past years, some research found that hypoxia response and hypoxia-inducible factors (HIFs) play critical roles in the pathogenesis of DN. Hypoxia-inducible factors (HIFs) HIF-1, HIF-2, and HIF-3 are the main mediators of metabolic responses to the state of hypoxia, which seems to be the one of the earliest events in the occurrence and progression of diabetic kidney disease (DKD). The abnormal activity of HIFs seems to be of crucial importance in the pathogenesis of diseases, including nephropathies. Studies using transcriptome analysis confirmed by metabolome analysis revealed that HIF stabilizers (HIF-prolyl hydroxylase inhibitors) are novel therapeutic agents used to treat anemia in CKD patients that not only increase endogenous erythropoietin production, but also could act by counteracting the metabolic alterations in incipient diabetic kidney disease and relieve oxidative stress in the renal tissue. In this review, we present the newest data regarding hypoxia response and HIF involvement in the pathogenesis of diabetic nephropathy and new therapeutic insights, starting from improving kidney oxygen homeostasis.
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28
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Della Rocca Y, Fonticoli L, Rajan TS, Trubiani O, Caputi S, Diomede F, Pizzicannella J, Marconi GD. Hypoxia: molecular pathophysiological mechanisms in human diseases. J Physiol Biochem 2022; 78:739-752. [PMID: 35870078 PMCID: PMC9684243 DOI: 10.1007/s13105-022-00912-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 07/14/2022] [Indexed: 12/01/2022]
Abstract
Abstract
Hypoxia, a low O2 tension, is a fundamental feature that occurs in physiological events as well as pathophysiological conditions, especially mentioned for its role in the mechanism of angiogenesis, glucose metabolism, and cell proliferation/survival. The hypoxic state through the activation of specific mechanisms is an aggravating circumstance commonly noticed in multiple sclerosis, cancer, heart disease, kidney disease, liver disease, lung disease, and in inflammatory bowel disease. On the other hand, hypoxia could play a key role in tissue regeneration and repair of damaged tissues, especially by acting on specific tissue stem cells, but their features may result as a disadvantage when it is concerned for neoplastic stem cells. Furthermore, hypoxia could also have a potential role in tissue engineering and regenerative medicine due to its capacity to improve the performance of biomaterials. The current review aims to highlight the hypoxic molecular mechanisms reported in different pathological conditions to provide an overview of hypoxia as a therapeutic agent in regenerative and molecular therapy.
Graphical abstract
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Affiliation(s)
- Ylenia Della Rocca
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy
| | - Luigia Fonticoli
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy
| | | | - Oriana Trubiani
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy
| | - Sergio Caputi
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy
| | - Francesca Diomede
- Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy.
| | - Jacopo Pizzicannella
- Cardiology Intensive Care Unit, "Ss. Annunziata" Hospital, ASL02 Lanciano-Vasto-Chieti, Chieti, Italy
| | - Guya Diletta Marconi
- Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy
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29
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Upregulation of Thioredoxin Reductase 1 Expression by Flavan-3-Ols Protects Human Kidney Proximal Tubular Cells from Hypoxia-Induced Cell Death. Antioxidants (Basel) 2022; 11:antiox11071399. [PMID: 35883890 PMCID: PMC9311547 DOI: 10.3390/antiox11071399] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 07/15/2022] [Accepted: 07/16/2022] [Indexed: 01/13/2023] Open
Abstract
Renal hypoxia and its associated oxidative stress is a common pathway for the development of kidney diseases, and using dietary antioxidants such as flavan-3-ols to prevent kidney failure has received much attention. This study investigates the molecular mechanism by which flavan-3-ols prevent hypoxia-induced cell death in renal tubular epithelial cells. Human kidney proximal tubular cells (HKC-8) were exposed to hypoxia (1% O2) in the presence of flavan-3-ols (catechin, epicatechin, procyanidin B1, and procyanidin B2). Cell death was examined using flow cytometric analysis. Gene expression was determined using a PCR array and Western blotting, and its network and functions were investigated using STRING databases. Here, we show that the cytoprotective activity of catechin was the highest among these flavan-3-ols against hypoxia-induced cell death in cultured HKC-8 cells. Exposure of HKC-8 cells to hypoxia induced oxidative stress leading to up-regulation of DUOX2, NOX4, CYBB and PTGS2 and down-regulation of TXNRD1 and HSP90AA1. Treatment with catechin or other flavan-3-ols prevented the down-regulation of TXNRD1 expression in hypoxic HKC-8 cells. Overexpression of TXNRD1 prevented hypoxia-induced cell death, and inactivation of TXNRD1 with TRi-1, a specific TXNRD1 inhibitor, reduced the catechin cytoprotection against hypoxia-induced HKC-8 cell death. In conclusion, flavan-3-ols prevent hypoxia-induced cell death in human proximal tubular epithelial cells, which might be mediated by their maintenance of TXNRD1 expression, suggesting that enhancing TXNRD1 expression or activity may become a novel therapeutic strategy to prevent hypoxia-induced kidney damage.
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Sun P, Huang R, Qin Z, Liu F. Influence of Tangeretin on the Exponential Regression of Inflammation and Oxidative Stress in Streptozotocin-Induced Diabetic Nephropathy. Appl Biochem Biotechnol 2022; 194:3914-3929. [PMID: 35567707 DOI: 10.1007/s12010-022-03920-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/14/2022] [Indexed: 01/08/2023]
Abstract
Diabetes is an amalgamation of metabolic disorders marked by hyperglycemia. Over time diabetes brings up several other complications with it like cardiovascular disease, retinopathy, neuropathy, and nephropathy. among which diabetic nephropathy (DN) is the one we are concerned about in the present study. Diabetes management requires following a healthy lifestyle with proper medication. Most of the anti-diabetic drugs available at present come with adverse side effects. Nature has provided us with several components that are anti-diabetic in nature which has fewer or no side effects and tangeretin is one among them. Tangeretin is a natural flavonoid abundantly present in orange peel and tangerines. Our study is designed to evaluate tangeretin, as an anti-diabetic medication especially for patients suffering from diabetic nephropathy. The procured healthy rats were first divided into four groups: the group I was maintained as healthy control and the others were subjected to the induction of diabetes by i.p. injection of streptozotocin (STZ) at the concentration of 55mg/kg b.wt .Then, the diabetic rats were further divided into three groups: group II was used as the diabetic control rats and the group III and group IV were administered with tangeretin (25mg/kg b.wt) and positive control drug metformin (150mg/kg b.wt) for 8 weeks. The body weight, blood glucose, and serum insulin levels were estimated at week 0 and week 8. Reactive oxygen species (ROS) inhibitory effect, antioxidant, antilipidemic, nephroprotective, and anti-inflammatory effects of tangeretin on the diabetic-induced rats were evaluated at the end of week 8 in addition to the histopathological assessment of the sections of the kidneys of the experimental rats. All the test results concluded that tangeretin was able to significantly decelerate the progression of DN in STZ-induced diabetic rats.
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Affiliation(s)
- Pei Sun
- Department of Endocrinology, Central Hospital Affiliated to Shandong First Medical University, No. 105, Jiefang Road, Jinan City, Shandong, 250013, China
| | - Ran Huang
- Department of Kidney Disease Unit & Dialysis, Central Hospital Affiliated to Shandong First Medical University, No. 105, Jiefang Road, Jinan City, Shandong, 250013, China
| | - Zifu Qin
- Department of Health, Vertigo Examination Room, Central Hospital Affiliated to Shandong First Medical University, No. 105, Jiefang Road, Jinan City, Shandong, 250013, China
| | - Fang Liu
- Department of Kidney Disease Unit & Dialysis, Central Hospital Affiliated to Shandong First Medical University, No. 105, Jiefang Road, Jinan City, Shandong, 250013, China.
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Curran CS, Kopp JB. Aryl Hydrocarbon Receptor Mechanisms Affecting Chronic Kidney Disease. Front Pharmacol 2022; 13:782199. [PMID: 35237156 PMCID: PMC8882872 DOI: 10.3389/fphar.2022.782199] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 01/14/2022] [Indexed: 12/25/2022] Open
Abstract
The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix transcription factor that binds diverse endogenous and xenobiotic ligands, which regulate AHR stability, transcriptional activity, and cell signaling. AHR activity is strongly implicated throughout the course of chronic kidney disease (CKD). Many diverse organic molecules bind and activate AHR and these ligands are reported to either promote glomerular and tubular damage or protect against kidney injury. AHR crosstalk with estrogen, peroxisome proliferator-activated receptor-γ, and NF-κB pathways may contribute to the diversity of AHR responses during the various forms and stages of CKD. The roles of AHR in kidney fibrosis, metabolism and the renin angiotensin system are described to offer insight into CKD pathogenesis and therapies.
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Affiliation(s)
- Colleen S. Curran
- Critical Care Medicine Department, Clinical Center, NIH, Bethesda, MD, United States
| | - Jeffrey B. Kopp
- Kidney Disease Section, NIDDK, NIH, Bethesda, MD, United States
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Mantri Y, Jokerst JV. Impact of skin tone on photoacoustic oximetry and tools to minimize bias. BIOMEDICAL OPTICS EXPRESS 2022; 13:875-887. [PMID: 35284157 PMCID: PMC8884230 DOI: 10.1364/boe.450224] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 01/13/2022] [Accepted: 01/14/2022] [Indexed: 05/02/2023]
Abstract
The major optical absorbers in tissue are melanin and oxy/deoxy-hemoglobin, but the impact of skin tone and pigmentation on biomedical optics is still not completely understood or adequately addressed. Melanin largely governs skin tone with higher melanin concentration in subjects with darker skin tones. Recently, there has been extensive debate on the bias of pulse oximeters when used with darker subjects. Photoacoustic (PA) imaging can measure oxygen saturation similarly as pulse oximeters and could have value in studying this bias. More importantly, it can deconvolute the signal from the skin and underlying tissue. Here, we studied the impact of skin tone on PA signal generation, depth penetration, and oximetry. Our results show that subjects with darker skin tones exhibit significantly higher PA signal at the skin surface, reduced penetration depth, and lower oxygen saturation compared to subjects with lighter skin tones. We then suggest a simple way to compensate for these signal differences.
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Affiliation(s)
- Yash Mantri
- Department of Bioengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA
| | - Jesse V. Jokerst
- Department of Nanoengineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA
- Material Science Department, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA
- Department of Radiology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA
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Erythrocyte transglutaminase-2 combats hypoxia and chronic kidney disease by promoting oxygen delivery and carnitine homeostasis. Cell Metab 2022; 34:299-316.e6. [PMID: 35108516 PMCID: PMC9380699 DOI: 10.1016/j.cmet.2021.12.019] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Revised: 09/29/2021] [Accepted: 12/21/2021] [Indexed: 02/03/2023]
Abstract
Due to lack of nuclei and de novo protein synthesis, post-translational modification (PTM) is imperative for erythrocytes to regulate oxygen (O2) delivery and combat tissue hypoxia. Here, we report that erythrocyte transglutminase-2 (eTG2)-mediated PTM is essential to trigger O2 delivery by promoting bisphosphoglycerate mutase proteostasis and the Rapoport-Luebering glycolytic shunt for adaptation to hypoxia, in healthy humans ascending to high altitude and in two distinct murine models of hypoxia. In a pathological hypoxia model with chronic kidney disease (CKD), eTG2 is critical to combat renal hypoxia-induced reduction of Slc22a5 transcription and OCNT2 protein levels via HIF-1α-PPARα signaling to maintain carnitine homeostasis. Carnitine supplementation is an effective and safe therapeutic approach to counteract hypertension and progression of CKD by enhancing erythrocyte O2 delivery. Altogether, we reveal eTG2 as an erythrocyte protein stabilizer orchestrating O2 delivery and tissue adaptive metabolic reprogramming and identify carnitine-based therapy to mitigate hypoxia and CKD progression.
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Cheng YQ, Yue YX, Cao HM, Geng WC, Wang LX, Hu XY, Li HB, Bian Q, Kong XL, Liu JF, Kong DL, Guo DS, Wang YB. Coassembly of hypoxia-sensitive macrocyclic amphiphiles and extracellular vesicles for targeted kidney injury imaging and therapy. J Nanobiotechnology 2021; 19:451. [PMID: 34961540 PMCID: PMC8714429 DOI: 10.1186/s12951-021-01192-w] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 12/07/2021] [Indexed: 12/01/2022] Open
Abstract
Background Hypoxia is a major contributor to global kidney diseases. Targeting hypoxia is a promising therapeutic option against both acute kidney injury and chronic kidney disease; however, an effective strategy that can achieve simultaneous targeted kidney hypoxia imaging and therapy has yet to be established. Herein, we fabricated a unique nano-sized hypoxia-sensitive coassembly (Pc/C5A@EVs) via molecular recognition and self-assembly, which is composed of the macrocyclic amphiphile C5A, the commercial dye sulfonated aluminum phthalocyanine (Pc) and mesenchymal stem cell-excreted extracellular vesicles (MSC-EVs). Results In murine models of unilateral or bilateral ischemia/reperfusion injury, MSC-EVs protected the Pc/C5A complex from immune metabolism, prolonged the circulation time of the complex, and specifically led Pc/C5A to hypoxic kidneys via surface integrin receptor α4β1 and αLβ2, where Pc/C5A released the near-infrared fluorescence of Pc and achieved enhanced hypoxia-sensitive imaging. Meanwhile, the coassembly significantly recovered kidney function by attenuating cell apoptosis, inhibiting the progression of renal fibrosis and reducing tubulointerstitial inflammation. Mechanistically, the Pc/C5A coassembly induced M1-to-M2 macrophage transition by inhibiting the HIF-1α expression in hypoxic renal tubular epithelial cells (TECs) and downstream NF-κB signaling pathway to exert their regenerative effects. Conclusion This synergetic nanoscale coassembly with great translational potential provides a novel strategy for precise kidney hypoxia diagnosis and efficient kidney injury treatment. Furthermore, our strategy of coassembling exogenous macrocyclic receptors with endogenous cell-derived membranous structures may offer a functional platform to address multiple clinical needs. Graphical Abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s12951-021-01192-w.
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Affiliation(s)
- Yuan-Qiu Cheng
- Nankai University School of Medicine, Tianjin, 300071, China
| | - Yu-Xin Yue
- College of Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, China
| | - Hong-Mei Cao
- Nankai University School of Medicine, Tianjin, 300071, China.,Key Laboratory of Radiopharmacokinetics for Innovative Drugs, Chinese Academy of Medical Sciences and Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, China
| | - Wen-Chao Geng
- College of Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, China
| | - Lan-Xing Wang
- Nankai University School of Medicine, Tianjin, 300071, China
| | - Xin-Yue Hu
- College of Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, China
| | - Hua-Bin Li
- College of Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, China
| | - Qiang Bian
- National Pesticide Engineering Research Center, College of Chemistry, Nankai University, Tianjin, 300071, China
| | - Xiang-Lei Kong
- College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, China
| | - Jian-Feng Liu
- Key Laboratory of Radiopharmacokinetics for Innovative Drugs, Chinese Academy of Medical Sciences and Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, China
| | - De-Ling Kong
- The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China
| | - Dong-Sheng Guo
- College of Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, China.
| | - Yue-Bing Wang
- Nankai University School of Medicine, Tianjin, 300071, China. .,Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China.
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A Comparison of GFR Calculated by Cockcroft-Gault vs. MDRD Formula in the Prognostic Assessment of Patients with Acute Pulmonary Embolism. DISEASE MARKERS 2021; 2021:6655958. [PMID: 34925647 PMCID: PMC8674072 DOI: 10.1155/2021/6655958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 11/15/2021] [Accepted: 11/17/2021] [Indexed: 11/17/2022]
Abstract
Introduction Risk stratification is mandatory for optimal management of patients with acute pulmonary embolism (APE). Previous studies indicated that renal dysfunction predicts outcome and can improve risk assessment in APE. Aim The aim of the study was a comparison of estimated glomerular filtration rate (eGFR) formulas, MDRD, and Cockcroft-Gault (CG), in the prognostic assessment of patients with APE. Materials and Methods Data from 2274 (1147 M/1127 F, median 71 years) hospitalised patients with APE prospectively included in a multicenter, observational, cohort study were analysed. A serum creatinine measurement as a routine laboratory parameter at the cooperating centers and eGFR calculation were performed on admission. Patients were followed for 180 days. The primary outcome was death from any cause within 30 days. Results The eGFR levels assessed by both, MDRD (eGFRMDRD) and CG formula (eGFRCG), were highest in patients with low-risk APE and lowest in high-risk APE. The eGFR (using both methods) was significantly lower in nonsurvivors compared to survivors. Using a threshold of <60 ml/min/1.73 m2, eGFRMDRD revealed the primary outcome with sensitivity 67%, specificity 52%, PPV 8%, and NPV 97%, while eGFRCG had a sensitivity 62%, specificity 62%, PPV 8.6%, and NPV 96%. The area under the ROC curve for eGFRCG tended to be higher than that for eGFRMDRD: 0.658 (95% CI: 0.608-0.709) vs. 0.631 (95% CI: 0.578-0.683), p = 0.12. A subanalysis of ROC curves in a population above 65 yrs showed a higher AUC for eGFRCG than based on MDRD. Kaplan-Meier analysis showed a worse long-term outcome in patients with impaired renal function. Conclusion eGFRMDRD and eGFRCG assessed on admission significant short- and long-term mortality predictors in patients with APE. The eGFRCG seems to be a slightly better 30-day mortality predictor than eGFRMDRD in the elderly.
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Kan C, Lu X, Zhang R. Effects of hypoxia on bone metabolism and anemia in patients with chronic kidney disease. World J Clin Cases 2021; 9:10616-10625. [PMID: 35004993 PMCID: PMC8686129 DOI: 10.12998/wjcc.v9.i34.10616] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 08/12/2021] [Accepted: 10/25/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Abnormal bone metabolism and renal anemia seriously affect the prognosis of patients with chronic kidney disease (CKD). Existing studies have mostly addressed the pathogenesis and treatment of bone metabolism abnormality and anemia in patients with CKD, but few have evaluated their mutual connection. Administration of exogenous erythropoietin to CKD patients with anemia used to be the mainstay of therapeutic approaches; however, with the availability of hypoxia-inducible factor (HIF) stabilizers such as roxadustat, more therapeutic choices for renal anemia are expected in the future. However, the effects posed by the hypoxic environment on both CKD complications remain incompletely understood. AIM To summarize the relationship between renal anemia and abnormal bone metabolism, and to discuss the influence of hypoxia on bone metabolism. METHODS CNKI and PubMed searches were performed using the key words "chronic kidney disease," "abnormal bone metabolism," "anemia," "hypoxia," and "HIF" to identify relevant articles published in multiple languages and fields. Reference lists from identified articles were reviewed to extract additional pertinent articles. Then we retrieved the Abstract and Introduction and searched the results from the literature, classified the extracted information, and summarized important information. Finally, we made our own conclusions. RESULTS There is a bidirectional relationship between renal anemia and abnormal bone metabolism. Abnormal vitamin D metabolism and hyperparathyroidism can affect bone metabolism, blood cell production, and survival rates through multiple pathways. Anemia will further attenuate the normal bone growth. The hypoxic environment regulates bone morphogenetic protein, vascular endothelial growth factor, and neuropilin-1, and affects osteoblast/osteoclast maturation and differentiation through bone metabolic changes. Hypoxia preconditioning of mesenchymal stem cells (MSCs) can enhance their paracrine effects and promote fracture healing. Concurrently, hypoxia reduces the inhibitory effect on osteocyte differentiation by inhibiting the expression of fibroblast growth factor 23. Hypoxia potentially improves bone metabolism, but it still carries potential risks. The optimal concentration and duration of hypoxia remain unclear. CONCLUSION There is a bidirectional relationship between renal anemia and abnormal bone metabolism. Hypoxia may improve bone metabolism but the concentration and duration of hypoxia remain unclear and need further study.
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Affiliation(s)
- Chao Kan
- Department of Clinical Medicine, Changchun University of Chinese Medicine, Changchun 130000, Jilin Province, China
| | - Xu Lu
- Department of Clinical Medicine, Changchun University of Chinese Medicine, Changchun 130000, Jilin Province, China
| | - Rui Zhang
- Department of Nephrology, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai 519070, Guangdong Province, China
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Bassan A, Alves VM, Amberg A, Anger LT, Beilke L, Bender A, Bernal A, Cronin MT, Hsieh JH, Johnson C, Kemper R, Mumtaz M, Neilson L, Pavan M, Pointon A, Pletz J, Ruiz P, Russo DP, Sabnis Y, Sandhu R, Schaefer M, Stavitskaya L, Szabo DT, Valentin JP, Woolley D, Zwickl C, Myatt GJ. In silico approaches in organ toxicity hazard assessment: Current status and future needs for predicting heart, kidney and lung toxicities. COMPUTATIONAL TOXICOLOGY (AMSTERDAM, NETHERLANDS) 2021; 20:100188. [PMID: 35721273 PMCID: PMC9205464 DOI: 10.1016/j.comtox.2021.100188] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
Abstract
The kidneys, heart and lungs are vital organ systems evaluated as part of acute or chronic toxicity assessments. New methodologies are being developed to predict these adverse effects based on in vitro and in silico approaches. This paper reviews the current state of the art in predicting these organ toxicities. It outlines the biological basis, processes and endpoints for kidney toxicity, pulmonary toxicity, respiratory irritation and sensitization as well as functional and structural cardiac toxicities. The review also covers current experimental approaches, including off-target panels from secondary pharmacology batteries. Current in silico approaches for prediction of these effects and mechanisms are described as well as obstacles to the use of in silico methods. Ultimately, a commonly accepted protocol for performing such assessment would be a valuable resource to expand the use of such approaches across different regulatory and industrial applications. However, a number of factors impede their widespread deployment including a lack of a comprehensive mechanistic understanding, limited in vitro testing approaches and limited in vivo databases suitable for modeling, a limited understanding of how to incorporate absorption, distribution, metabolism, and excretion (ADME) considerations into the overall process, a lack of in silico models designed to predict a safe dose and an accepted framework for organizing the key characteristics of these organ toxicants.
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Affiliation(s)
- Arianna Bassan
- Innovatune srl, Via Giulio Zanon 130/D, 35129 Padova, Italy
| | - Vinicius M. Alves
- The National Institute of Environmental Health Sciences, Division of the National Toxicology Program, Research Triangle Park, NC 27709, United States
| | - Alexander Amberg
- Sanofi, R&D Preclinical Safety Frankfurt, Industriepark Hoechst, D-65926 Frankfurt am Main, Germany
| | - Lennart T. Anger
- Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, United States
| | - Lisa Beilke
- Toxicology Solutions Inc., San Diego, CA, United States
| | - Andreas Bender
- AI and Data Analytics, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, UK
- Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United States
| | | | - Mark T.D. Cronin
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, L3 3AF, UK
| | - Jui-Hua Hsieh
- The National Institute of Environmental Health Sciences, Division of the National Toxicology Program, Research Triangle Park, NC 27709, United States
| | | | - Raymond Kemper
- Nuvalent, One Broadway, 14th floor, Cambridge, MA 02142, United States
| | - Moiz Mumtaz
- Agency for Toxic Substances and Disease Registry, US Department of Health and Human Services, Atlanta, GA, United States
| | - Louise Neilson
- Broughton Nicotine Services, Oak Tree House, West Craven Drive, Earby, Lancashire BB18 6JZ UK
| | - Manuela Pavan
- Innovatune srl, Via Giulio Zanon 130/D, 35129 Padova, Italy
| | - Amy Pointon
- Functional and Mechanistic Safety, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Cambridge, UK
| | - Julia Pletz
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, L3 3AF, UK
| | - Patricia Ruiz
- Agency for Toxic Substances and Disease Registry, US Department of Health and Human Services, Atlanta, GA, United States
| | - Daniel P. Russo
- The Rutgers Center for Computational and Integrative Biology, Camden, NJ 08102, United States
- Department of Chemistry, Rutgers University, Camden, NJ 08102, United States
| | - Yogesh Sabnis
- UCB Biopharma SRL, Chemin du Foriest, B-1420 Braine-l’Alleud, Belgium
| | - Reena Sandhu
- SafeDose Ltd., 20 Dundas Street West, Suite 921, Toronto, Ontario M5G2H1, Canada
| | - Markus Schaefer
- Sanofi, R&D Preclinical Safety Frankfurt, Industriepark Hoechst, D-65926 Frankfurt am Main, Germany
| | - Lidiya Stavitskaya
- US Food and Drug Administration, Center for Drug Evaluation and Research, Silver Spring, MD 20993, USA
| | | | | | - David Woolley
- ForthTox Limited, PO Box 13550, Linlithgow, EH49 7YU, UK
| | - Craig Zwickl
- Transendix LLC, 1407 Moores Manor, Indianapolis, IN 46229, United States
| | - Glenn J. Myatt
- Instem, 1393 Dublin Road, Columbus, OH 43215, United States
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Shubham S, Kumar M, Sarma DK, Kumawat M, Verma V, Samartha RM, Tiwari RR. Role of air pollution in chronic kidney disease: an update on evidence, mechanisms and mitigation strategies. Int Arch Occup Environ Health 2021; 95:897-908. [PMID: 34716808 DOI: 10.1007/s00420-021-01808-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 10/05/2021] [Indexed: 01/19/2023]
Abstract
Air pollution results from a variable and complex mixture of harmful gases and suspended particles and is the most worrisome of all environmental hazards. It is implicated in several non -communicable diseases and is recognized to be a public health problem. Though the initial exposure to air pollution is through the respiratory system, kidneys are thought to be exposed to higher concentrations owing to their filtration function. Chronic kidney disease is the insidious end result of several disease processes which cumulatively form a large healthcare burden, particularly in low- and middle-income countries. There is a growing body of evidence that air pollution may be a contributing factor that leads to CKD by not only its direct effects, but can also compound the effect of other factors/diseases causing kidney injury. PM2.5 exposure particularly has been implicated, although there is some evidence regarding other air pollutants as well. These pollutants are thought to act on kidneys through several interlinked systemic pathways and mechanisms which individually and collectively damage the nephrons. Long-term exposures seem to gradually diminish renal function and lead to end-stage renal disease. A thorough understanding of the mechanism of kidney injury is the key for formulating and implementing effective strategies for reducing this burden. Maintaining the air quality, promoting education, improving health quality and promotion of targeted nephroprotective measures through effective policy and research support are required in addressing this global public health problem.
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Affiliation(s)
- Swasti Shubham
- Indian Council of Medical Research-National Institute for Research in Environmental Health, Bhopal, India.
| | - Manoj Kumar
- Indian Council of Medical Research-National Institute for Research in Environmental Health, Bhopal, India
| | - Devojit Kumar Sarma
- Indian Council of Medical Research-National Institute for Research in Environmental Health, Bhopal, India
| | - Manoj Kumawat
- Indian Council of Medical Research-National Institute for Research in Environmental Health, Bhopal, India
| | - Vinod Verma
- Sanjay Gandhi Post Graduate Institute, Lucknow, India
| | - R M Samartha
- Bhopal Memorial Hospital & Research Centre, Bhopal, India
| | - R R Tiwari
- Indian Council of Medical Research-National Institute for Research in Environmental Health, Bhopal, India
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Mishra J, Khan W, Ahmad S, Misra K. Supercritical Carbon Dioxide Extracts of Cordyceps sinensis: Chromatography-based Metabolite Profiling and Protective Efficacy Against Hypobaric Hypoxia. Front Pharmacol 2021; 12:628924. [PMID: 34512317 PMCID: PMC8426348 DOI: 10.3389/fphar.2021.628924] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 08/10/2021] [Indexed: 11/18/2022] Open
Abstract
The toxicity and disposal concerns of organic solvents used in conventional extraction purposes has entailed the need for greener alternatives. Among such techniques, supercritical fluid extraction (SFE) has gained popularity by yielding extracts of high purity in a much faster manner. Carbon dioxide (CO2) is generally preferred as a supercritical solvent because of its lower temperature requirements, better diffusivity and easy removal. The present study describes the characterization of supercritical CO2 extracts of Indian variety of Cordyceps sinensis (CS)- a high-altitude medicinal mushroom widely revered in traditional medicine for its extensive anti-hypercholesterolemic, anti-inflammatory, anti-proliferative and energy-enhancing properties. Experimental parameters viz. 300 and 350 bar of extraction pressure, 60°C of temperature, 0.4°L/h CO2 of flow rate and use of 1% (v/v) of ethanol as entrainer were optimized to prepare three different extracts namely, CSF1, CSF2 and CSF3. High-performance thin-layer chromatography (HPTLC) was used for assessing the quality of all the extracts in terms of cordycepin, the pivot biomarker compound in CS. Characterization by HPTLC and GC-MS confirmed the presence of flavonoids and nucleobases and, volatile organic compounds (VOCs), respectively. The chromatographic data acquired from metabolite profiling were subjected to chemometric analysis in an open source R studio which illustrated interrelatedness between CSF1 and CSF2 in terms of two major principal components. i.e. Dim 1 and Dim 2 whose values were 40.33 and 30.52% in variables factor map plotted using the HPTLC-generated retardation factor values. The factor maps based on retention times of the VOCs exhibited a variance of Dim 1 = 43.95% and Dim 2 = 24.85%. Furthermore, the extracts demonstrated appreciable antibacterial activity against Escherichia coli and Salmonella typhi by generation of reactive oxygen species (ROS), protein leakage and efflux pump inhibition within bacterial pathogens. CSFs were elucidated to be significantly cytoprotective (p < 0.05) in a simulated hypobaric hypoxia milieu (0.5% oxygen). CSF2 showed the best results by effectively improving the viability of human embryonic kidney (HEK 293) cells to 82.36 ± 1.76% at an optimum dose of 100 µg/ml. Levels of hypoxia inducible factor-1 alpha (HIF-1α) were modulated four-fold upon supplementation with CSF2. The results collectively evinced that the CSF extracts are substantially bioactive and could be effectively utilized as mycotherapeutics for multiple bioeffects.
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Affiliation(s)
| | - Washim Khan
- Bioactive Natural Products Laboratory, Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India.,National Center for Natural Products Research, The University of Mississippi, Oxford, MS, United States
| | - Sayeed Ahmad
- Bioactive Natural Products Laboratory, Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
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Olaniyi KS, Sabinari IW, Olatunji LA. Oral ethinylestradiol–levonorgestrel therapy counteracts fructose-induced renal metabolic impairment in female rats. ENDOCRINE AND METABOLIC SCIENCE 2021. [DOI: 10.1016/j.endmts.2021.100099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Risk factors and mortality of acute kidney injury within 1 month after lung transplantation. Sci Rep 2021; 11:17399. [PMID: 34462528 PMCID: PMC8405794 DOI: 10.1038/s41598-021-96889-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 07/08/2021] [Indexed: 02/07/2023] Open
Abstract
After lung transplantation (LT), some patients are at risk of acute kidney injury (AKI), which is associated with worse outcomes and increased mortality. Previous studies focused on AKI development from 72 h to 1 week within LT, and reported main risk factors for AKI such as intraoperative hypotension, need of ECMO support, ischemia time or longer time on waiting list. However, this period interval rarely reflects medical risk factors probably happen in longer post-operative period. So, in this study we aimed to describe the incidence and risk factor of AKI within post-operative 1 month, which is longer follow up duration. Among 161 patients who underwent LT at Severance hospital in Seoul, Korea from October 2012 to September 2017, 148 patients were retrospectively enrolled. Multivariable logistic regression and Cox proportional hazard models were utilized. Among 148 patients, 59 (39.8%) developed AKI within 1-month after LT. Stage I or II, and stage III AKI were recorded in 26 (17.5%) and 33 (22.2%), respectively. We also classified AKI according to occurrence time, within 1 week as early AKI, from 1 week within 1 month was defined as late AKI. AKI III usually occurred within 7 days after transplantation (early vs. late AKI III, 72.5% vs 21.1%). Risk factor for AKI development was pre-operative anemia, higher units of red blood cells transfused during surgery, colistin intravenous infusion for treating multi drug resistant pathogens were independent risk factors for AKI development. Post-operative bleeding, grade 3 PGD within 72 h, and sepsis were more common complication in the AKI group. Patients with AKI III ([24/33] 72.7%) had significantly higher 1-year mortality than the no-AKI ([18/89] 20.2%), and AKI I or II group ([9/26] 34.6%), log-rank test, P < 0.001). AKI was associated with worse post-operative outcome, 3-month, and 1-year mortality after LT. Severity of AKI was usually determined in early post op period (ex. within 7 days) after LT, so optimal post-operative management as well as recipients selection should be considered.
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Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases. Biomolecules 2021; 11:biom11091259. [PMID: 34572472 PMCID: PMC8465464 DOI: 10.3390/biom11091259] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 08/17/2021] [Accepted: 08/23/2021] [Indexed: 02/08/2023] Open
Abstract
Mitochondria are complex organelles that orchestrate several functions in the cell. The primary function recognized is energy production; however, other functions involve the communication with the rest of the cell through reactive oxygen species (ROS), calcium influx, mitochondrial DNA (mtDNA), adenosine triphosphate (ATP) levels, cytochrome c release, and also through tricarboxylic acid (TCA) metabolites. Kidney function highly depends on mitochondria; hence mitochondrial dysfunction is associated with kidney diseases. In addition to oxidative phosphorylation impairment, other mitochondrial abnormalities have been described in kidney diseases, such as induction of mitophagy, intrinsic pathway of apoptosis, and releasing molecules to communicate to the rest of the cell. The TCA cycle is a metabolic pathway whose primary function is to generate electrons to feed the electron transport system (ETS) to drives energy production. However, TCA cycle metabolites can also release from mitochondria or produced in the cytosol to exert different functions and modify cell behavior. Here we review the involvement of some of the functions of TCA metabolites in kidney diseases.
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Azinheira Nobrega Cruz N, Gonçalves de Oliveira LC, Tedesco Silva Junior H, Osmar Medina Pestana J, Casarini DE. Angiotensin-Converting Enzyme 2 in the Pathogenesis of Renal Abnormalities Observed in COVID-19 Patients. Front Physiol 2021; 12:700220. [PMID: 34497535 PMCID: PMC8419418 DOI: 10.3389/fphys.2021.700220] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 08/03/2021] [Indexed: 01/08/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) was first reported in late December 2019 in Wuhan, China. The etiological agent of this disease is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the high transmissibility of the virus led to its rapid global spread and a major pandemic (ongoing at the time of writing this review). The clinical manifestations of COVID-19 can vary widely from non-evident or minor symptoms to severe acute respiratory syndrome and multi-organ damage, causing death. Acute kidney injury (AKI) has been recognized as a common complication of COVID-19 and in many cases, kidney replacement therapy (KRT) is required. The presence of kidney abnormalities on hospital admission and the development of AKI are related to a more severe presentation of COVID-19 with higher mortality rate. The high transmissibility and the broad spectrum of clinical manifestations of COVID-19 are in part due to the high affinity of SARS-CoV-2 for its receptor, angiotensin (Ang)-converting enzyme 2 (ACE2), which is widely expressed in human organs and is especially abundant in the kidneys. A debate on the role of ACE2 in the infectivity and pathogenesis of COVID-19 has emerged: Does the high expression of ACE2 promotes higher infectivity and more severe clinical manifestations or does the interaction of SARS-CoV-2 with ACE2 reduce the bioavailability of the enzyme, depleting its biological activity, which is closely related to two important physiological systems, the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS), thereby further contributing to pathogenesis. In this review, we discuss the dual role of ACE2 in the infectivity and pathogenesis of COVID-19, highlighting the effects of COVID-19-induced ACE2 depletion in the renal physiology and how it may lead to kidney injury. The ACE2 downstream regulation of KKS, that usually receives less attention, is discussed. Also, a detailed discussion on how the triad of symptoms (respiratory, inflammatory, and coagulation symptoms) of COVID-19 can indirectly promote renal injury is primary aborded.
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Affiliation(s)
| | | | | | | | - Dulce Elena Casarini
- Nephrology Division, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
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Allardyce H, Kuhn D, Hernandez-Gerez E, Hensel N, Huang YT, Faller K, Gillingwater TH, Quondamatteo F, Claus P, Parson SH. Renal pathology in a mouse model of severe Spinal Muscular Atrophy is associated with downregulation of Glial Cell-Line Derived Neurotrophic Factor (GDNF). Hum Mol Genet 2021; 29:2365-2378. [PMID: 32588893 DOI: 10.1093/hmg/ddaa126] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 06/11/2020] [Accepted: 06/12/2020] [Indexed: 12/16/2022] Open
Abstract
Spinal muscular atrophy (SMA) occurs as a result of cell-ubiquitous depletion of the essential survival motor neuron (SMN) protein. Characteristic disease pathology is driven by a particular vulnerability of the ventral motor neurons of the spinal cord to decreased SMN. Perhaps not surprisingly, many other organ systems are also impacted by SMN depletion. The normal kidney expresses very high levels of SMN protein, equivalent to those found in the nervous system and liver, and levels are dramatically lowered by ~90-95% in mouse models of SMA. Taken together, these data suggest that renal pathology may be present in SMA. We have addressed this using an established mouse model of severe SMA. Nephron number, as assessed by gold standard stereological techniques, was significantly reduced. In addition, morphological assessment showed decreased renal vasculature, particularly of the glomerular capillary knot, dysregulation of nephrin and collagen IV, and ultrastructural changes in the trilaminar filtration layers of the nephron. To explore the molecular drivers underpinning this process, we correlated these findings with quantitative PCR measurements and protein analyses of glial cell-line-derived neurotrophic factor, a crucial factor in ureteric bud branching and subsequent nephron development. Glial cell-line-derived neurotrophic factor levels were significantly reduced at early stages of disease in SMA mice. Collectively, these findings reveal significant renal pathology in a mouse model of severe SMA, further reinforcing the need to develop and administer systemic therapies for this neuromuscular disease.
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Affiliation(s)
- Hazel Allardyce
- Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK.,Euan Macdonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK
| | - Daniela Kuhn
- Hannover Medical School, Institute of Neuroanatomy and Cell Biology, Hannover 30625, Germany
| | - Elena Hernandez-Gerez
- Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK.,Euan Macdonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK
| | - Niko Hensel
- Hannover Medical School, Institute of Neuroanatomy and Cell Biology, Hannover 30625, Germany.,Center for Systems Neuroscience (ZSN) Hannover, University of Veterinary Medicine Hannover, Hannover 30559, Germany
| | - Yu-Ting Huang
- Euan Macdonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK.,Edinburgh Medical School: Biomedical Sciences, College of Medicine & Veterinary Medicine, University of Edinburgh, Edinburgh EH8 9AG, UK
| | - Kiterie Faller
- Euan Macdonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK.,Edinburgh Medical School: Biomedical Sciences, College of Medicine & Veterinary Medicine, University of Edinburgh, Edinburgh EH8 9AG, UK
| | - Thomas H Gillingwater
- Euan Macdonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK.,Edinburgh Medical School: Biomedical Sciences, College of Medicine & Veterinary Medicine, University of Edinburgh, Edinburgh EH8 9AG, UK
| | - Fabio Quondamatteo
- Anatomy Facility, School of Life Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK
| | - Peter Claus
- Hannover Medical School, Institute of Neuroanatomy and Cell Biology, Hannover 30625, Germany.,Center for Systems Neuroscience (ZSN) Hannover, University of Veterinary Medicine Hannover, Hannover 30559, Germany
| | - Simon H Parson
- Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK.,Euan Macdonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK
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Spencer S, Wheeler-Jones C, Elliott J. Hypoxia and chronic kidney disease: Possible mechanisms, therapeutic targets, and relevance to cats. Vet J 2021; 274:105714. [PMID: 34252550 DOI: 10.1016/j.tvjl.2021.105714] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 07/01/2021] [Accepted: 07/06/2021] [Indexed: 10/20/2022]
Abstract
There is mounting evidence that kidney ischaemia/hypoxia plays an important role in feline chronic kidney disease (CKD) development and progression, as well as in human disease and laboratory animal models. Ischaemic acute kidney injury is widely accepted as a cause of CKD in people and data from laboratory species has identified some of the pathways underlying this continuum. Experimental kidney ischaemia in cats results in morphological changes, namely chronic tubulointerstitial inflammation, tubulointerstitial fibrosis, and tubular atrophy, akin to those observed in naturally-occurring CKD. Multiple situations are envisaged that could result in acute or chronic episodes of kidney hypoxia in cats, while risk factors identified in epidemiological studies provide further support that kidney hypoxia contributes to spontaneously occurring feline CKD. This review evaluates the evidence for the role of kidney ischaemia/hypoxia in feline CKD and the proposed mechanisms and consequences of kidney hypoxia. As no effective treatments exist that substantially slow or prevent feline CKD progression, there is a need for novel therapeutic strategies. Targeting kidney hypoxia is one such promising approach, with therapies including those that attenuate the hypoxia-inducible factor (HIF) pathway already being utilised in human CKD.
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Affiliation(s)
- Sarah Spencer
- Comparative Biomedical Sciences, The Royal Veterinary College, Royal College Street, London NW1 0TU, UK.
| | - Caroline Wheeler-Jones
- Comparative Biomedical Sciences, The Royal Veterinary College, Royal College Street, London NW1 0TU, UK
| | - Jonathan Elliott
- Comparative Biomedical Sciences, The Royal Veterinary College, Royal College Street, London NW1 0TU, UK
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Karatzas A, Godevenos A, Lavdas E. Renal Symptoms and Kidney Impairment Due to Dissecting Abdominal Aortic Aneurysm. Urology 2021; 154:e9-e10. [PMID: 34029604 DOI: 10.1016/j.urology.2021.05.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 04/23/2021] [Accepted: 05/09/2021] [Indexed: 11/24/2022]
Abstract
Renal artery stenosis leading to renal damage is not uncommon among patients with abdominal aortic aneurysm and has been identified in 20-38% of patients with aortic disease. In otherwise normal renal arteries, a thrombus at the origin of the artery may decrease the renal blood flow, leading to renal colic and kidney impairment. We report a rare case of a patient with renal symptoms associated with dissecting aortic aneurysm, with thrombus at the level of the origin of an otherwise normal right renal artery.
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Affiliation(s)
- Anastasios Karatzas
- Department of Urology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
| | - Apostolos Godevenos
- Department of Radiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
| | - Eleftherios Lavdas
- Department of Medical Radiological Technologists, Technological Education Institute of Athens, Greece; Department of Radiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
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Prikhodko VA, Selizarova NO, Okovityi SV. [Molecular mechanisms for hypoxia development and adaptation to it. Part I]. Arkh Patol 2021; 83:52-61. [PMID: 33822555 DOI: 10.17116/patol20218302152] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Hypoxia is a typical pathological process characterized by the occurrence of oxygen deficiency in tissues and cells and accompanied by the development of immediate and delayed compensatory and adaptive reactions. Reprogramming of the mitochondrial electron transport chain (ETC) function is one the most essential regulatory mechanisms that allow for immediate adaptation to hypoxia. Succinic acid, or succinate, is involved in this process not only as one of the intermediates of the tricarboxylic acid (TAC) cycle, but also as a signaling molecule. In this connection, the purpose of this review was to systematize the available data on the molecular mechanisms for the development of hypoxia and its adaptation at the ETC/TAC coupling site, as well as on the role of succinic acid in these processes.
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Affiliation(s)
- V A Prikhodko
- Saint Petersburg State Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation, Saint Petersburg, Russia
| | - N O Selizarova
- Saint Petersburg State Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation, Saint Petersburg, Russia
| | - S V Okovityi
- Saint Petersburg State Chemical and Pharmaceutical University of the Ministry of Health of the Russian Federation, Saint Petersburg, Russia
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Transcriptome Analysis Reveals the AhR, Smad2/3, and HIF-1α Pathways as the Mechanism of Ochratoxin A Toxicity in Kidney Cells. Toxins (Basel) 2021; 13:toxins13030190. [PMID: 33800744 PMCID: PMC7999264 DOI: 10.3390/toxins13030190] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 02/25/2021] [Accepted: 03/05/2021] [Indexed: 12/11/2022] Open
Abstract
Ochratoxin A (OTA) is a mycotoxin occurring in foods consumed by humans. Recently, there has been growing global concern regarding OTA toxicity. The main target organ of OTA is the kidney, but the mechanism underlying renal toxicity is not well known. In this study, human-derived proximal tubular epithelial cells, HK-2 cells, were used for RNA-sequencing (RNA-seq) and transcriptome analysis. In total, 3193 differentially expressed genes were identified upon treatment with 200 nM OTA in HK-2 cells; of these, 2224 were upregulated and 969 were downregulated. Transcriptome analysis revealed that OTA significantly affects hypoxia, epithelial-mesenchymal transition (EMT), apoptosis, and xenobiotic metabolism pathways in kidney cells. Quantitative real-time PCR analysis showed gene expression patterns similar to RNA-seq analysis. Expression of EMT markers (E-cadherin and fibronectin), apoptosis markers (caspase-3 and Bax), and kidney injury molecule-1 (KIM-1) was suppressed by inhibiting AhR expression using siRNA, and the related transcription factors, Smad2/3, and HIF-1α were downregulated. Smad2/3 suppression with siRNA could inhibit fibronetcin, caspase-3, Bax, and KIM-1 expression. Fibronetcin, caspase-3, Bax, and KIM-1 expression could be increased with HIF-1α suppression with siRNA. Taken together, these findings suggest that OTA-mediated kidney toxicity via the AhR-Smad2/3-HIF-1α signaling pathways leads to induction of EMT, apoptosis, and kidney injury.
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Bailey MD, Jin GX, Carniato F, Botta M, Allen MJ. Rational Design of High-Relaxivity Eu II -Based Contrast Agents for Magnetic Resonance Imaging of Low-Oxygen Environments. Chemistry 2021; 27:3114-3118. [PMID: 33226696 PMCID: PMC7902434 DOI: 10.1002/chem.202004450] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Revised: 11/21/2020] [Indexed: 01/01/2023]
Abstract
Metal-based contrast agents for magnetic resonance imaging present a promising avenue to image hypoxia. EuII -based contrast agents have a unique biologically relevant redox couple, EuII/III , that distinguishes this metal for use in hypoxia imaging. To that end, we investigated a strategy to enhance the contrast-enhancing capabilities of EuII -based cryptates in magnetic resonance imaging by controlling the rotational dynamics. Two dimetallic, EuII -containing cryptates were synthesized to test the efficacy of rigid versus flexible coupling strategies. A flexible strategy to dimerization led to a modest (114 %) increase in contrast enhancement per Eu ion (60 MHz, 298 K), but a rigid linking strategy led to an excellent (186 %) increase in contrast enhancement despite this compound's having the smaller molecular mass of the two dimetallic complexes. We envision the rigid linking strategy to be useful in the future design of potent EuII -based contrast agents for magnetic resonance imaging.
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Affiliation(s)
- Matthew D Bailey
- Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, MI, 48202, USA
| | - Guo-Xia Jin
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for, Chemical Imaging, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan, 250014, P. R. China
| | - Fabio Carniato
- Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale "Amedeo Avogadro", Viale T. Michel 11, 15121, Alessandria, Italy
| | - Mauro Botta
- Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale "Amedeo Avogadro", Viale T. Michel 11, 15121, Alessandria, Italy
| | - Matthew J Allen
- Department of Chemistry, Wayne State University, 5101 Cass Avenue, Detroit, MI, 48202, USA
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Pływaczewska M, Pruszczyk P, Kostrubiec M. Does kidney function matter in pulmonary thromboembolism management? Cardiol J 2021; 29:858-865. [PMID: 33470418 PMCID: PMC9550328 DOI: 10.5603/cj.a2021.0005] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/30/2020] [Accepted: 12/22/2020] [Indexed: 11/25/2022] Open
Abstract
Cardiovascular circulation and kidney function are closely interrelated. The impairment of renal function is a well-known hazard of increased mortality and morbidity of patients with heart failure or coronary artery disease. Acute pulmonary embolism (APE) impacts pulmonary and systemic circulation, and can severely impair functions of other organs, including kidneys, as a result of hypoxemia and increased venous pressure. Previous studies indicate that renal dysfunction predicts short- and long-term outcomes and can improve the risk assessment in APE. However, renal function should also be cautiously considered during the diagnostic workup because the contrast-induced nephropathy after computed tomography pulmonary angiography is noticed more frequently in APE. Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but imminent complication of APE. This condition promotes renal impairment by increasing venous pressure and decreasing glomerular filtration. The renal function improvement and serum creatinine concentration reduction were noted in CTEPH subgroup with glomerular filtration rate ≤ 60 mL/min/1.73 m2 after successful treatment. In this review, we present the essential research results on the kidney function in thromboembolism disease.
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Affiliation(s)
| | - Piotr Pruszczyk
- Department of Inter nal Medicine and Car diology, Medical University of Warsaw, Poland
| | - Maciej Kostrubiec
- Department of Inter nal Medicine and Car diology, Medical University of Warsaw, Poland
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