Dynamic modulations of urinary sphingolipid and glycerophospholipid levels in COVID-19 and correlations with COVID-19-associated kidney injuries

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: Nov. 10, 2022

Among various complications of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome 2 (SARS-CoV-2), renal complications, namely COVID-19-associated kidney injuries, are related to the mortality COVID-19.In this retrospective cross-sectional study, we measured sphingolipids and glycerophospholipids, which have been shown possess potent biological properties, using liquid chromatography-mass spectrometry in 272 urine samples collected longitudinally from 91 COVID-19 subjects 95 control without infectious diseases, elucidate pathogenesis injuries.The urinary levels C18:0, C18:1, C22:0, C24:0 ceramides, sphingosine, dihydrosphingosine, phosphatidylcholine, lysophosphatidylcholine, lysophosphatidic acid, phosphatidylglycerol decreased, while those phosphatidylserine, lysophosphatidylserine, phosphatidylethanolamine, lysophosphatidylethanolamine increased patients with mild COVID-19, especially during early phase (day 1-3), suggesting that these modulations might reflect direct effects infection SARS-CoV-2. Generally, sphingomyelin, dihydrosphingosine L-phosphate, lysophosphatidylethanolamine, phosphatidylglycerol, lysophosphatidylglycerol, phosphatidylinositol, lysophosphatidylinositol increased, later phase, their result injuries accompanying COVID-19.Considering properties an understanding will help us understand mechanisms causing as well general may prompt researchers develop laboratory tests for predicting maximum severity and/or novel reagents suppress COVID-19.

Language: Английский

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Intercellular mitochondrial transfer as a means of revitalizing injured glomerular endothelial cells

World Journal of Stem Cells, Journal Year: 2022, Volume and Issue: 14(9), P. 729 - 743

Published: Sept. 23, 2022

Recent studies have demonstrated that mesenchymal stem cells (MSCs) can rescue injured target via mitochondrial transfer. However, it has not been fully understood how bone marrow-derived MSCs repair glomeruli in diabetic kidney disease (DKD).To explore the transfer involved of glomerular endothelial (GECs) by MSCs, both vitro and vivo.In experiments were performed to investigate effect co-culture with on high glucose-induced GECs. The mitochondria was visua lized using fluorescent microscopy. GECs freshly sorted ultimately tested for apoptosis, viability, mRNA expression real-time reverse transcri ptase-polymerase chain reaction, protein western blot, function. Moreover, streptozotocin-induced DKD rats infused renal function oxidative stress detected an automatic biochemical analyzer related-detection kits after 2 wk. Kidney histology analyzed hematoxylin eosin, periodic acid-Schiff, immunohistochemical staining.Fluorescence imaging confirmed transferred when co-cultured vitro. We found proliferation, improved following co-culture. Additionally, decreased pro-inflammatory cytokines [interleukin (IL)-6, IL-1β, tumor necrosis factor-α] pro-apoptotic factors (caspase 3 Bax). Mitochondrial also enhanced superoxide dismutase 2, B cell lymphoma-2, glutathione peroxidase (GPx) 3, mitofusin inhibited reactive oxygen species (ROS) dynamin-related 1 expression. Furthermore, significantly ameliorated functional parameters (blood urea nitrogen serum creatinine) production malondialdehyde, advanced glycation end products, ROS, whereas they increased levels GPx vivo. In addition, significant reductions basement membrane interstitial fibrosis observed MSC treatment.MSCs rejuvenate damaged improvement pathological changes may be related mechanism

Language: Английский

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Modulations of bioactive lipids and their receptors in postmortem Alzheimer’s disease brains

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: Dec. 9, 2022

Background Analyses of brain samples from Alzheimer’s disease (AD) patients may be expected to help us improve our understanding the pathogenesis AD. Bioactive lipids, including sphingolipids, glycerophospholipids, and eicosanoids/related mediators have been demonstrated exert potent physiological actions involved in various human diseases. In this cross-sectional study, we attempted elucidate associations these bioactive lipids with pathogenesis/pathology AD through postmortem studies brains. Methods We measured levels brains (AD brains), Cerad score B (Cerad-b control subjects (control using a liquid chromatography-mass spectrometry method; also mRNA specific receptors for same specimens. Results The several species sphingomyelins ceramides were higher Cerad-b Levels lysophosphatidic acids (LPAs), lysophosphatidylcholine, lysophosphatidylserine, lysophosphatidylethanolamine (LPE), lysophosphatidylinositol, phosphatidylcholine, phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidylinositol, phosphatidylglycerol especially high brains, while those lysophosphatidylglycerol (LPG) Several eicosanoids, metabolites prostaglandin E2, oxylipins, epoxide, DHA EPA, such as resolvins, modulated Among lipid mediators, S1P2, S1P5, LPA1, LPA2, LPA6, P2Y10, GPR174, EP1, DP1, DP2, IP, FP, TXA2r lower and/or ceramides, LPC, LPI, PE, PS showed strong positive correlations Aβ contents, LPG rather presence senile plaques neurofibrillary tangles. A discriminant analysis revealed that is important LPE/PE axis Cerad-b. Conclusions Comprehensive lipidomics, together measurement receptor expression provided novel evidence AD, which facilitate future translational research reverse research.

Language: Английский

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Klotho inhibits renal ox-LDL deposition via IGF-1R/RAC1/OLR1 signaling to ameliorate podocyte injury in diabetic kidney disease

Cardiovascular Diabetology, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 27, 2023

Abstract Objective Diabetic kidney disease (DKD) is characterized by the abnormal deposition of oxidized low-density lipoprotein (ox-LDL), which contributes to podocyte damage. Klotho, an aging suppressor that plays a critical role in protecting podocytes DKD, mainly expressed tubular epithelium and secreted blood. However, it has not been established whether Klotho can alleviate injury inhibiting renal ox-LDL deposition, potential molecular mechanisms require further investigation. Methods We conducted comprehensive analysis serum biopsy samples obtained from patients diagnosed with DKD. Additionally, explore underlying mechanism kidneys, we employed mouse model DKD genotype induced streptozotocin (STZ). Furthermore, meticulous vitro experiments on gain insights into specific within kidney. Results Our groundbreaking study unveiled remarkable ability soluble form effectively inhibit high glucose-induced affected Subsequent investigations elucidated achieved this inhibition reducing expression insulin/insulin-like growth factor 1 receptor (IGF-1R), consequently leading decrease Ras-related C3 botulinum toxin substrate (RAC1) enhancement mitochondrial function. Ultimately, series events culminated significant reduction (OLR1), thereby resulting notable Conclusion findings suggested had mitigate reduced glomerulus modulating IGF-1R/RAC1/OLR1 signaling. These results provided valuable could inform development novel strategies for diagnosing treating Graphical

Language: Английский

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Detection of Fast Decliner of Diabetic Kidney Disease Using Chiral Amino Acid Profiling: A Pilot Study

Chemistry & Biodiversity, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Biomarkers for the prediction of diabetic kidney disease are still unsatisfactory. Although D-amino acids have been shown to reflect conditions, their efficacy in treating (DKD) has not demonstrated. This study explored potential role as progression markers DKD, an aspect addressed previously. We performed comprehensive acid measurements and collected longitudinal estimated glomerular filtration rate (eGFR) data 135 patients. defined fast decliners (FDs) patients exhibiting >10% decline from baseline eGFR per year compared levels FDs non-FDs. Then, we verified that could predict independent creatinine levels. In with disease, D-serine, D-alanine, D-proline were only detected blood, while 15 urine. Using supervised orthogonal partial least squares analysis, blood D-serine urine identified features characterizing disease. Baseline ratios did differ between FD non-FD groups; however, short-term changes differed. emphasized significance a prognostic marker previous research.

Language: Английский

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