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Morimoto Y, Inoue K, Itoh S. Reactivity of copper(I) complexes supported by tripodal nitrogen-containing tetradentate ligands toward gaseous diatomic molecules, NO, CO and O 2. Dalton Trans 2025; 54:5327-5333. [PMID: 40012511 DOI: 10.1039/d4dt03001j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2025]
Abstract
Series of Cu(I) complexes supported by nitrogen-based tetradentate ligands were examined for their reactivity toward nitric oxide (NO). The copper complexes generated the corresponding Cu(II)-nitrite complexes in the presence of an excess molar amount of NO. A higher reactivity of the Cu(I) complexes toward NO was observed with a more negative Cu(I/II) redox potential, same as their reactivity toward O2 and CO, while [CuI(tepa)]+ with the most positive oxidation potential only reacted with NO among the diatomic gaseous molecules (NO, O2, and CO) examined in this study. DFT studies explained that the reactivity of the Cu-NO complex was the key to its selectivity rather than its coordination bond stability.
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Affiliation(s)
- Yuma Morimoto
- Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
| | - Keisuke Inoue
- Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
| | - Shinobu Itoh
- Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
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Grönroos R, Eggertsen R, Bernhardsson S, Praetorius Björk M. Effects of beetroot juice on blood pressure in hypertension according to European Society of Hypertension Guidelines: A systematic review and meta-analysis. Nutr Metab Cardiovasc Dis 2024; 34:2240-2256. [PMID: 39069465 DOI: 10.1016/j.numecd.2024.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Revised: 06/11/2024] [Accepted: 06/13/2024] [Indexed: 07/30/2024]
Abstract
AIMS It has been suggested that nitrate-rich beetroot juice (BRJ) reduces blood pressure (BP) in various populations. We aimed to investigate the effect of BRJ on BP in adults with hypertension according to the European Society of Hypertension Guidelines (clinical BP ≥ 140/≥ 90 mmHg) and whether BRJ can be considered as an adjunct to hypertension drug treatment, by conducting a meta-analysis of randomized controlled trials. DATA SYNTHESIS PubMed, SCOPUS, Medline Ovid, Cinahl, Cochrane Library and Web of Science were searched from inception until April 13, 2024 to identify randomized controlled trials of BRJ versus placebo, water, or no intake. Risk of bias was assessed using a standardized appraisal instrument from the Swedish Agency for Health Technology and Assessment of Social Services, which is based on the Cochrane risk-of-bias tool for randomized trials. The pooled BP effect size was calculated using random effects models and meta-regression. Certainty of evidence was assessed using GRADE. Eleven trials (349 patients) were included. BRJ yielded a significant reduction in clinical systolic BP compared with placebo mean difference (MD) -5.31 mmHg (95% CI -7.46, -3.16; I2 = 64%, GRADE ⊕⊕OO). There was no significant effect on clinical diastolic BP or 24-h BP outcomes, and the heterogeneity was moderate to high. CONCLUSIONS Daily ingestion of 200-800 mg of nitrate from BRJ may reduce clinical systolic BP in hypertensive individuals with no sign of development of tolerance. Certainty of evidence is low, and results should be interpreted with caution.
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Affiliation(s)
- Rebecca Grönroos
- Region Västra Götaland, Närhälsan Mölnlycke Healthcare Centre, Gothenburg, Sweden.
| | - Robert Eggertsen
- Region Västra Götaland, Research, Education, Development and Innovation, Primary Health Care, Gothenburg, Sweden; School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Susanne Bernhardsson
- Region Västra Götaland, Research, Education, Development and Innovation, Primary Health Care, Gothenburg, Sweden; Department of Health and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Marcus Praetorius Björk
- Region Västra Götaland, Research, Education, Development and Innovation, Primary Health Care, Gothenburg, Sweden; School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Kocgozlu L, Mutschler A, Tallet L, Calligaro C, Knopf-Marques H, Lebaudy E, Mathieu E, Rabineau M, Gribova V, Senger B, Vrana NE, Lavalle P. Cationic homopolypeptides: A versatile tool to design multifunctional antimicrobial nanocoatings. Mater Today Bio 2024; 28:101168. [PMID: 39221202 PMCID: PMC11364137 DOI: 10.1016/j.mtbio.2024.101168] [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: 03/26/2024] [Revised: 07/24/2024] [Accepted: 07/27/2024] [Indexed: 09/04/2024] Open
Abstract
Postoperative infections are the most common complications faced by surgeons after implant surgery. To address this issue, an emerging and promising approach is to develop antimicrobial coatings using antibiotic substitutes. We investigated the use of polycationic homopolypeptides in a layer-by-layer coating combined with hyaluronic acid (HA) to produce an effective antimicrobial shield. The three peptide-based polycations used to make the coatings, poly(l-arginine) (PAR), poly(l-lysine), and poly(l-ornithine), provided an efficient antibacterial barrier by a contact-killing mechanism against Gram-positive, Gram-negative, and antibiotic-resistant bacteria. Moreover, this activity was higher for homopolypeptides containing 30 amino-acid residues per polycation chain, emphasizing the impact of the polycation chain length and its mobility in the coatings to deploy its contact-killing antimicrobial properties. However, the PAR-containing coating emerged as the best candidate among the three selected polycations, as it promoted cell adhesion and epithelial monolayer formation. It also stimulated nitric oxide production in endothelial cells, thereby facilitating angiogenesis and subsequent tissue regeneration. More interestingly, bacteria did not develop a resistance to PAR and (PAR/HA) also inhibited the proliferation of eukaryotic pathogens, such as yeasts. Furthermore, in vivo investigations on a (PAR/HA)-coated hernia mesh implanted on a rabbit model confirmed that the coating had antibacterial properties without causing chronic inflammation. These impressive synergistic activities highlight the strong potential of PAR/HA coatings as a key tool in combating bacteria, including those resistant to conventional antibiotics and associated to medical devices.
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Affiliation(s)
- Leyla Kocgozlu
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1121, Strasbourg, France
- Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, France
| | - Angela Mutschler
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1121, Strasbourg, France
- Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, France
| | - Lorène Tallet
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1121, Strasbourg, France
- Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, France
| | | | - Helena Knopf-Marques
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1121, Strasbourg, France
- Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, France
| | - Eloïse Lebaudy
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1121, Strasbourg, France
- Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, France
| | - Eric Mathieu
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1121, Strasbourg, France
- Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, France
| | - Morgane Rabineau
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1121, Strasbourg, France
- Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, France
| | - Varvara Gribova
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1121, Strasbourg, France
- Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, France
| | - Bernard Senger
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1121, Strasbourg, France
- Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, France
| | | | - Philippe Lavalle
- Institut National de la Santé et de la Recherche Médicale, UMR_S 1121, Strasbourg, France
- Université de Strasbourg, Faculté de Chirurgie Dentaire, Strasbourg, France
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Wan W, Wang N. Polarized benzene rings can promote the interaction between CaM and the CaMBD region of nNOS. Front Mol Neurosci 2024; 17:1461272. [PMID: 39290828 PMCID: PMC11405375 DOI: 10.3389/fnmol.2024.1461272] [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: 07/08/2024] [Accepted: 08/23/2024] [Indexed: 09/19/2024] Open
Abstract
Introduction The neuronal nitric oxide synthase (nNOS) subtype of nitric oxide synthase (NOS) is an enzyme required for learning and memory. Overactivation of nNOS can lead to oxidative/nitrite stress, which is complicit in the pathophysiology of various neurological and psychiatric disorders. Previous studies have shown that calmodulin (CaM) forms complexes with Ca2+ and binds to the calmodulin-binding domain (CaMBD) of nNOS, thereby upregulating its catalytic activity in hippocampal neurons. To date, there has been no explanation for the non-covalent interactions in the CaMBD-CaM binding structure model of nNOS. Methods In this study, we aimed to investigate the intrinsic factors involved in the binding of CaM to NOS-CaMBD and designed interfering peptides based on the N0 peptide structure of the original nNOS-CaMBD sequence: N1 (obtained from the L734F mutation), N2 (obtained from the F731Y and F740Y mutations), and N3 (obtained from the F731L, V738L, and F740L mutations). We employed homology modeling to construct six CaM-peptide complex models, aiming to elucidate the roles of key amino acid residues within the N0 peptide in its interaction with CaM by means of molecular dynamics simulations. The effect of the peptides on the activation and release of NO by nNOS in neurons was assessed using murine primary neuronal cells. Results When measuring neuronal NO content, it was found that adding N2 and N3 to cultivated neurons significantly increased nNOS activity, leading to the increased NO production. We found that interfering peptides could stably bind to CaM. Among them, N2 and CaM exhibited the strongest binding ability, indicating that the polarized benzene ring significantly enhanced the binding between nNOS-CaMBD and CaM. Conversely, the binding ability between N0 and CaM was the weakest, as they exhibited the worst polar contact, weakest hydrogen bonding, and the lowest binding free energy. The simulation results also highlighted several important amino acid residues: The K76 of CaM plays an important role in polar contact and hydrogen bonding formation, the L734 residue suppressed model flexibility to a certain extent and had an adverse effect on the overall binding free energy of the model. These results, compared with the results of cellular NO content, a preliminary verification of the antagonistic competitive mechanism between CaM allosteric activation of nNOS and SUMOylation hyperactivation was performed. Discussion In summary, this study explored the ability and mode of action of key residues in nNOS-CaMBD on the binding of interfering peptides to CaM, thereby providing new structural perspectives for the activation of nNOS by CaM and recommendations for drug design targeting the specific inhibition of nNOS.
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Affiliation(s)
- Wei Wan
- Research Center for Biochemistry and Molecular Biology, Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou, Jiangsu, China
- National Demonstration Center of Experimental Basic Medical Science Education, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Nan Wang
- Research Center for Biochemistry and Molecular Biology, Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou, Jiangsu, China
- National Demonstration Center of Experimental Basic Medical Science Education, Xuzhou Medical University, Xuzhou, Jiangsu, China
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Prasad S, Singh S, Menge S, Mohapatra I, Kim S, Helland L, Singh G, Singh A. Gut redox and microbiome: charting the roadmap to T-cell regulation. Front Immunol 2024; 15:1387903. [PMID: 39234241 PMCID: PMC11371728 DOI: 10.3389/fimmu.2024.1387903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Accepted: 07/31/2024] [Indexed: 09/06/2024] Open
Abstract
The gastrointestinal (GI) tract redox environment, influenced by commensal microbiota and bacterial-derived metabolites, is crucial in shaping T-cell responses. Specifically, metabolites from gut microbiota (GM) exhibit robust anti-inflammatory effects, fostering the differentiation and regulation of CD8+ tissue-resident memory (TRM) cells, mucosal-associated invariant T (MAIT) cells, and stabilizing gut-resident Treg cells. Nitric oxide (NO), a pivotal redox mediator, emerges as a central regulator of T-cell functions and gut inflammation. NO impacts the composition of the gut microbiome, driving the differentiation of pro-inflammatory Th17 cells and exacerbating intestinal inflammation, and supports Treg expansion, showcasing its dual role in immune homeostasis. This review delves into the complex interplay between GI redox balance and GM metabolites, elucidating their profound impact on T-cell regulation. Additionally, it comprehensively emphasizes the critical role of GI redox, particularly reactive oxygen species (ROS) and NO, in shaping T-cell phenotype and functions. These insights offer valuable perspectives on disease mechanisms and potential therapeutic strategies for conditions associated with oxidative stress. Understanding the complex cross-talk between GI redox, GM metabolites, and T-cell responses provides valuable insights into potential therapeutic avenues for immune-mediated diseases, underscoring the significance of maintaining GI redox balance for optimal immune health.
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Affiliation(s)
- Sujata Prasad
- Translational Division, MLM Labs, LLC, Oakdale, MN, United States
| | - Shilpi Singh
- Department of Neurosurgery, University of Minnesota, Minneapolis, MN, United States
| | - Samuel Menge
- Department of Surgery, Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN, United States
| | - Iteeshree Mohapatra
- Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN, United States
| | - Stefan Kim
- Department of Neurosurgery, University of Minnesota, Minneapolis, MN, United States
| | - Logan Helland
- Department of Neurosurgery, University of Minnesota, Minneapolis, MN, United States
| | - Gatikrushna Singh
- Department of Neurosurgery, University of Minnesota, Minneapolis, MN, United States
| | - Amar Singh
- Department of Surgery, Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN, United States
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Mohammadipour HS, Bagheri H, Babazadeh S, Khorshid M, Shooshtari Z, Shahri A. Evaluation and comparison of the effects of a new paste containing 8% L-Arginine and CaCO3 plus KNO3 on dentinal tubules occlusion and dental sensitivity: a randomized, triple blinded clinical trial study. BMC Oral Health 2024; 24:507. [PMID: 38685035 PMCID: PMC11059626 DOI: 10.1186/s12903-024-04298-3] [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: 01/31/2024] [Accepted: 04/26/2024] [Indexed: 05/02/2024] Open
Abstract
BACKGROUND Dentin hypersensitivity, often occurring after dental treatments or from erosive lesions, is a prevalent patient complaint. This study introduces a paste combining 8% L-arginine, calcium carbonate, and potassium nitrate to evaluate its impact on dentinal tubules occlusion, dentin permeability, and tooth sensitivity. METHODS Dentin surfaces from 24 third molars (thickness: 2 mm) were divided into two groups of 12. One received the experimental paste, while the other received a placebo without desensitizer. Permeability and sealing ability were assessed through scanning electron microscopy (SEM) and dentin permeability measurement. The pastes' effects on hypersensitivity were then examined in a triple-blind, randomized parallel-armed clinical trial with 16 eligible patients. Sensitivity to cold, touch, and spontaneous stimuli was recorded using the VAS scale at various intervals post-treatment. Statistical analysis was conducted using Shapiro-Wilk, Mann-Whitney U, Friedman, and Wilcoxon tests (α = 0.05). RESULTS The permeability test demonstrated a significant reduction in dentin permeability in the experimental group (P = 0.002) compared to the control (P = 0.178). SEM images revealed most dentinal tubules in the intervention samples to be occluded. Clinically, both groups showed a significant decrease in the three types of evaluated sensitivity throughout the study. However, no significant difference in sensitivities between the two groups was observed, with the exception of cold sensitivity at three months post-treatment (P = 0.054). CONCLUSION The innovative desensitizing paste featuring 8% L-arginine, calcium carbonate, and potassium nitrate effectively occluded dentinal tubules and reduced dentin permeability. It mitigated immediate and prolonged dentin hypersensitivity to various stimuli, supporting its potential role in managing dentin hypersensitivity. TRIAL REGISTRATION http://irct.ir : IRCT20220829055822N1, September 9th, 2022.
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Affiliation(s)
- Hamideh Sadat Mohammadipour
- Department of Restorative and Cosmetic Dentistry, Mashhad Dental School, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Bagheri
- Dental Materials Research Center, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Saber Babazadeh
- Department of Community Oral Health, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Zahra Shooshtari
- Dentist, Research Assistant, Dental Research Center, Mashhad Dental School, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Arsalan Shahri
- Dental Materials Research Center, Mashhad Dental School, Mashhad University of Medical Sciences, Mashhad, Iran.
- Mashhad dental school, Mashhad university of medical sciences university campus, P.O. Box: 9178613111, Mashhad, Iran.
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Um S, Lee J, Kim SJ, Cho KA, Kang KS, Kim SH. Xinghamide A, a New Cyclic Nonapeptide Found in Streptomyces xinghaiensis. Mar Drugs 2023; 21:509. [PMID: 37888444 PMCID: PMC10608500 DOI: 10.3390/md21100509] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 09/15/2023] [Accepted: 09/25/2023] [Indexed: 10/28/2023] Open
Abstract
Xinghamide A (1), a new nonapeptide, was discovered in Streptomyces xinghaiensis isolated from a halophyte, Suaeda maritima (L.) Dumort. Based on high-resolution mass and NMR spectroscopic data, the planar structure of 1 was established, and, in particular, the sequence of nine amino acids was determined with ROESY and HMBC NMR spectra. The absolute configurations of the α-carbon of each amino acid residue were determined with 1-fluoro-2,4-dinitrophenyl-l-and -d-leucine amide (Marfey's reagents) and 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl isothiocyanate, followed by LC-MS analysis. The anti-inflammatory activity of xinghamide A (1) was evaluated by inhibitory abilities against the nitric oxide (NO) secretion and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.
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Affiliation(s)
- Soohyun Um
- College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Republic of Korea; (S.U.); (J.L.); (K.A.C.)
| | - Jaeyoun Lee
- College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Republic of Korea; (S.U.); (J.L.); (K.A.C.)
| | - Sung Jin Kim
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea; (S.J.K.); (K.S.K.)
| | - Kyung A Cho
- College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Republic of Korea; (S.U.); (J.L.); (K.A.C.)
| | - Ki Sung Kang
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea; (S.J.K.); (K.S.K.)
| | - Seung Hyun Kim
- College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Republic of Korea; (S.U.); (J.L.); (K.A.C.)
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Mace EH, Kimlinger MJ, Billings FT, Lopez MG. Targeting Soluble Guanylyl Cyclase during Ischemia and Reperfusion. Cells 2023; 12:1903. [PMID: 37508567 PMCID: PMC10378692 DOI: 10.3390/cells12141903] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023] Open
Abstract
Ischemia and reperfusion (IR) damage organs and contribute to many disease states. Few effective treatments exist that attenuate IR injury. The augmentation of nitric oxide (NO) signaling remains a promising therapeutic target for IR injury. NO binds to soluble guanylyl cyclase (sGC) to regulate vasodilation, maintain endothelial barrier integrity, and modulate inflammation through the production of cyclic-GMP in vascular smooth muscle. Pharmacologic sGC stimulators and activators have recently been developed. In preclinical studies, sGC stimulators, which augment the reduced form of sGC, and activators, which activate the oxidized non-NO binding form of sGC, increase vasodilation and decrease cardiac, cerebral, renal, pulmonary, and hepatic injury following IR. These effects may be a result of the improved regulation of perfusion and decreased oxidative injury during IR. sGC stimulators are now used clinically to treat some chronic conditions such as heart failure and pulmonary hypertension. Clinical trials of sGC activators have been terminated secondary to adverse side effects including hypotension. Additional clinical studies to investigate the effects of sGC stimulation and activation during acute conditions, such as IR, are warranted.
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Affiliation(s)
- Eric H Mace
- Department of Surgery, Vanderbilt University Medical Center, Medical Center North, Suite CCC-4312, 1161 21st Avenue South, Nashville, TN 37232-2730, USA
| | - Melissa J Kimlinger
- Vanderbilt University School of Medicine, 428 Eskind Family Biomedical Library and Learning Center, Nashville, TN 37240-0002, USA
| | - Frederic T Billings
- Department of Anesthesiology, Division of Critical Care Medicine, Vanderbilt University Medical Center, Medical Arts Building, Suite 422, 1211 21st Avenue South, Nashville, TN 37212-1750, USA
| | - Marcos G Lopez
- Department of Anesthesiology, Division of Critical Care Medicine, Vanderbilt University Medical Center, Medical Arts Building, Suite 422, 1211 21st Avenue South, Nashville, TN 37212-1750, USA
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Kunst C, Schmid S, Michalski M, Tümen D, Buttenschön J, Müller M, Gülow K. The Influence of Gut Microbiota on Oxidative Stress and the Immune System. Biomedicines 2023; 11:biomedicines11051388. [PMID: 37239059 DOI: 10.3390/biomedicines11051388] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 05/04/2023] [Accepted: 05/05/2023] [Indexed: 05/28/2023] Open
Abstract
The human gastrointestinal tract is home to a complex microbial community that plays an important role in the general well-being of the entire organism. The gut microbiota generates a variety of metabolites and thereby regulates many biological processes, such as the regulation of the immune system. In the gut, bacteria are in direct contact with the host. The major challenge here is to prevent unwanted inflammatory reactions on one hand and on the other hand to ensure that the immune system can be activated when pathogens invade. Here the REDOX equilibrium is of utmost importance. This REDOX equilibrium is controlled by the microbiota either directly or indirectly via bacterial-derived metabolites. A balanced microbiome sorts for a stable REDOX balance, whereas dysbiosis destabilizes this equilibrium. An imbalanced REDOX status directly affects the immune system by disrupting intracellular signaling and promoting inflammatory responses. Here we (i) focus on the most common reactive oxygen species (ROS) and (ii) define the transition from a balanced REDOX state to oxidative stress. Further, we (iii) describe the role of ROS in regulating the immune system and inflammatory responses. Thereafter, we (iv) examine the influence of microbiota on REDOX homeostasis and how shifts in pro- and anti-oxidative cellular conditions can suppress or promote immune responses or inflammation.
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Affiliation(s)
- Claudia Kunst
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Bavaria, Germany
| | - Stephan Schmid
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Bavaria, Germany
| | - Marlen Michalski
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Bavaria, Germany
| | - Deniz Tümen
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Bavaria, Germany
| | - Jonas Buttenschön
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Bavaria, Germany
| | - Martina Müller
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Bavaria, Germany
| | - Karsten Gülow
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Bavaria, Germany
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Suvorava T, Metry S, Pick S, Kojda G. Alterations in endothelial nitric oxide synthase activity and their relevance to blood pressure. Biochem Pharmacol 2022; 205:115256. [DOI: 10.1016/j.bcp.2022.115256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 09/12/2022] [Accepted: 09/13/2022] [Indexed: 12/15/2022]
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The Differences of Metabolites in Different Parts of the Brain Induced by Shuxuetong Injection against Cerebral Ischemia-Reperfusion and Its Corresponding Mechanism. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:9465095. [PMID: 35815276 PMCID: PMC9259222 DOI: 10.1155/2022/9465095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 05/26/2022] [Accepted: 05/31/2022] [Indexed: 11/18/2022]
Abstract
Ischemic stroke is often associated with a large disease burden. The existence of ischemia-reperfusion injury brings great challenges to the treatment of ischemic stroke. The purpose of this study was to explore the differences of metabolites in different parts of the brain induced by Shuxuetong injection against cerebral ischemia-reperfusion and to extend the corresponding mechanism. The rats were modeled by transient middle cerebral artery occlusion (t-MCAO) operation, and the success of modeling was determined by neurological function score and TTC staining. UPLC-Q/TOF-MS metabolomics technique and multivariate statistical analysis were used to analyze the changes and differences of metabolites in the cortex and hippocampus of cerebral ischemia-reperfusion rats. Compared with the model group, the neurological function score and cerebral infarction volume of the Shuxuetong treatment group were significantly different. There were differences and changes in the metabolic distribution of the cortex and hippocampus in each group, the distribution within the group was relatively concentrated. The separation trend between the groups was obvious, and the distribution of the Shuxuetong treatment group was similar to that of the sham operation group. We identified 13 metabolites that were differentially expressed in the cortex, including glutamine, dihydroorotic acid, and glyceric acid. We also found five differentially expressed metabolites in the hippocampus, including glutamic acid and fumaric acid. The common metabolic pathways of Shuxuetong on the cortex and hippocampus were D-glutamine and D-glutamate metabolism and nitrogen metabolism, which showed inhibition of cortical glutamine and promotion of hippocampal glutamic acid. Specific pathways of Shuxuetong enriched in the cortex included glyoxylate and dicarboxylate metabolism and pyrimidine metabolism, which showed inhibition of glyceric acid and dihydroorotic acid. Specific pathways of Shuxuetong enriched in the hippocampus include arginine biosynthesis and citrate cycle (TCA cycle), which promotes fumaric acid. Shuxuetong injection can restore and adjust the metabolic disorder of the cortex and hippocampus in cerebral ischemia-reperfusion rats. The expression of Shuxuetong in different parts of the brain is different and correlated.
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Piacenza L, Zeida A, Trujillo M, Radi R. The superoxide radical switch in the biology of nitric oxide and peroxynitrite. Physiol Rev 2022; 102:1881-1906. [PMID: 35605280 DOI: 10.1152/physrev.00005.2022] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Lucìa Piacenza
- Departamento de Bioquímica, Facultad de Medicina; Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Uruguay
| | - Ari Zeida
- Departamento de Bioquímica, Facultad de Medicina; Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay
| | - Madia Trujillo
- Departamento de Bioquímica, Facultad de Medicina; Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay
| | - Rafael Radi
- Departamento de Bioquímica, Facultad de Medicina; Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay
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13
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Burdina EV, Gruntenko NE. Physiological Aspects of Wolbachia pipientis–Drosophila melanogaster Relationship. J EVOL BIOCHEM PHYS+ 2022. [DOI: 10.1134/s0022093022020016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Khaing A, Swe AT, Aung CL, Thwin MM, Sein MT. Expression of Endothelin-1 and Endothelial Nitric Oxide Synthase in Normal and Preeclamptic Placentae. REVISTA BRASILEIRA DE GINECOLOGIA E OBSTETRICIA : REVISTA DA FEDERACAO BRASILEIRA DAS SOCIEDADES DE GINECOLOGIA E OBSTETRICIA 2022; 44:125-132. [PMID: 35213910 PMCID: PMC9948136 DOI: 10.1055/s-0042-1742317] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
OBJECTIVE To investigate the expression of endothelin-1 (ET-1) and endothelial nitric oxide (NO) synthase (eNOS) in normal and preeclamptic (PE) placentae. METHODS The present cross-sectional analytical study was performed in normal and PE primigravidae (n = 10 in each group) who were admitted to the North Okkalapa General and Teaching Hospital from February 2019 to February 2020. Serum samples were collected immediately before delivery, and placental tissues were collected immediately after emergency or elective cesarean section. The expression of placental eNOS was measured by western blot, and the levels of ET-1 in placental tissue homogenates and in the serum were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS The PE group had significantly higher serum levels of ET-1 (median: 116.56 pg/mL; IQR: 89.14-159.62 pg/mL) than the normal group (median: 60.02 pg/mL; IQR: 50.89-94.37 pg/mL) (p < 0.05). However, statistically significant differences were not observed in the levels of ET-1 in placental tissue homogenates between normal and PE placentae (median: 0.007 pg/µg of total protein; IQR: 0.002-0.0123 pg/µg of total protein; and median: 0.005 pg/µg of total protein; IQR: 0.003-0.016 pg/µg of total protein respectively). The median and IQR values of relative placental eNOS expression were significantly higher in the PE group than in the normal group (p < 0.05). The serum levels of ET-1 level were not significantly correlated with placental ET-1 expression, and neither there was a significant correlation between placental ET-1 and eNOS expression in any of the groups. CONCLUSION The serum levels of ET-1 were significantly higher in PE pregnant women compared with normal pregnant women, while the ET-1 levels of placental tissue homogenates were not significantly different. Serum ET-1 rather than placental ET-1 might play a major role in the pathogenesis of PE.
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Affiliation(s)
- Aung Khaing
- Department of Physiology, University of Medicine 2, Yangon, The Republic of the Union of Myanmar
| | - Aye Thet Swe
- Department of Physiology, University of Medicine 2, Yangon, The Republic of the Union of Myanmar
| | - Cho Lwin Aung
- Department of Physiology, University of Medicine 2, Yangon, The Republic of the Union of Myanmar
| | - Mya Mya Thwin
- Physiology Unit, Universiti Sultan Zanial Abidin, Kuala Terengganu,Terengganu, Malaysia
| | - Mya Thanda Sein
- Department of Physiology, University of Medicine 2, Yangon, The Republic of the Union of Myanmar
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Akins JD, Richey RE, Campbell JC, Martin ZT, Olvera G, Brothers RM. Contributions of endothelin-1 and l-arginine to blunted cutaneous microvascular function in young, black women. Am J Physiol Heart Circ Physiol 2022; 322:H260-H268. [PMID: 34919455 PMCID: PMC8759956 DOI: 10.1152/ajpheart.00457.2021] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Non-Hispanic black (BL) individuals have the greatest prevalence of cardiovascular disease (CVD), relative to other racial/ethnic groups (e.g., non-Hispanic white population; WH), which may be secondary to blunted vascular function. Although women typically present with reduced CVD relative to men of the same racial/ethnic group, the prevalence is similar between BL women and men though the mechanisms differ. This study hypothesized that reduced microvascular function in young, BL women is associated with endothelin-1 (ET-1) overactivity or insufficient l-arginine bioavailability. Nine BL and nine WH women participated (age: 20 ± 2 vs. 22 ± 2 yr). Cutaneous microvascular function was assessed during 39°C local heating, whereas lactated Ringer's (control), BQ-123 (ET-1 receptor type A antagonist), BQ-788 (ET-1 receptor type B antagonist), or l-arginine were infused via intradermal microdialysis to modify cutaneous vascular conductance (CVC). Subsequent infusion of Nω-nitro-l-arginine methyl ester allowed for quantification of the nitric oxide (NO) contribution to vasodilation, whereas combined sodium nitroprusside and 43°C heating allowed for normalization to maximal CVC (%CVCmax). BL women had blunted %CVCmax and NO contribution to dilation during the 39°C plateau (P < 0.027 for both). BQ-123 improved this response through augmented NO-mediated dilation (P < 0.048 for both). BQ-788 and l-arginine did not alter the CVC responses (P > 0.835 for both) or the NO contribution (P > 0.371 for both). Cutaneous microvascular function is reduced in BL women, and ET-1 receptor type A may contribute to this reduced function. Further research is needed to better characterize these mechanisms in young, BL women.NEW & NOTEWORTHY Cardiovascular disease remains a burden in the United States non-Hispanic black (BL) population, although its manifestation through blunted vasodilation in this population is different between men and women. Accordingly, this study determined that reduced microvascular function in young, BL women may be partially controlled by endothelin-1 (ET-1) type A receptors, although neither type B receptors nor insufficient l-arginine bioavailability seems to contribute to this response. Accordingly, further research is needed to better characterize these ET-1 related mechanisms and illuminate other pathways that may contribute to this disparate vascular function in young, BL women.
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Affiliation(s)
- John D. Akins
- 1Department of Kinesiology, The University of Texas at Arlington, Arlington, Texas
| | - Rauchelle E. Richey
- 1Department of Kinesiology, The University of Texas at Arlington, Arlington, Texas,2Department of Integrative Physiology, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas
| | - Jeremiah C. Campbell
- 1Department of Kinesiology, The University of Texas at Arlington, Arlington, Texas
| | - Zachary T. Martin
- 1Department of Kinesiology, The University of Texas at Arlington, Arlington, Texas
| | - Guillermo Olvera
- 1Department of Kinesiology, The University of Texas at Arlington, Arlington, Texas,3Institute for Exercise and Environmental Medicine, Dallas, Texas
| | - R. Matthew Brothers
- 1Department of Kinesiology, The University of Texas at Arlington, Arlington, Texas
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Methods to Detect Nitric Oxide and Reactive Nitrogen Species in Biological Sample. METHODS IN MOLECULAR BIOLOGY (CLIFTON, N.J.) 2022; 2413:69-76. [PMID: 35044656 DOI: 10.1007/978-1-0716-1896-7_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Oxidative stress has been implicated in various human diseases, including cancer, mainly through the generation of reactive nitrogen species (RNS), such as nitric oxide (NO), nitrite, nitroxyl, s-nitrosothiols, and reactive oxygen species (ROS) such as peroxides, superoxide, and hydroxyl radicals. NO being the main player among RNS induced altered cellular molecules and metabolisms, thus making it important to understand and detect the generation of NO in biological samples. There are many methods for direct and indirect detection of NO; out of these most commonly used are spectrophotometric-based Griess assay and fluorescence probe-based assays. In this chapter, we summarize these routinely used methods to detect NO and various challenges associated with these methods.
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17
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Khan I, Bai Y, Zha L, Ullah N, Ullah H, Shah SRH, Sun H, Zhang C. Mechanism of the Gut Microbiota Colonization Resistance and Enteric Pathogen Infection. Front Cell Infect Microbiol 2021; 11:716299. [PMID: 35004340 PMCID: PMC8733563 DOI: 10.3389/fcimb.2021.716299] [Citation(s) in RCA: 103] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 11/26/2021] [Indexed: 12/26/2022] Open
Abstract
The mammalian gut microbial community, known as the gut microbiota, comprises trillions of bacteria, which co-evolved with the host and has an important role in a variety of host functions that include nutrient acquisition, metabolism, and immunity development, and more importantly, it plays a critical role in the protection of the host from enteric infections associated with exogenous pathogens or indigenous pathobiont outgrowth that may result from healthy gut microbial community disruption. Microbiota evolves complex mechanisms to restrain pathogen growth, which included nutrient competition, competitive metabolic interactions, niche exclusion, and induction of host immune response, which are collectively termed colonization resistance. On the other hand, pathogens have also developed counterstrategies to expand their population and enhance their virulence to cope with the gut microbiota colonization resistance and cause infection. This review summarizes the available literature on the complex relationship occurring between the intestinal microbiota and enteric pathogens, describing how the gut microbiota can mediate colonization resistance against bacterial enteric infections and how bacterial enteropathogens can overcome this resistance as well as how the understanding of this complex interaction can inform future therapies against infectious diseases.
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Affiliation(s)
- Israr Khan
- School of Life Sciences, Lanzhou University, Lanzhou, China
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, Lanzhou University, Lanzhou, China
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou, China
- Gansu Key Laboratory of Functional Genomics and Molecular Diagnosis, Lanzhou University, Lanzhou, China
- Cuiying Biomedical Research Centre, Lanzhou University Second Hospital, Lanzhou, China
| | - Yanrui Bai
- School of Life Sciences, Lanzhou University, Lanzhou, China
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, Lanzhou University, Lanzhou, China
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou, China
- Gansu Key Laboratory of Functional Genomics and Molecular Diagnosis, Lanzhou University, Lanzhou, China
- Cuiying Biomedical Research Centre, Lanzhou University Second Hospital, Lanzhou, China
| | - Lajia Zha
- School of Life Sciences, Lanzhou University, Lanzhou, China
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, Lanzhou University, Lanzhou, China
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou, China
- Gansu Key Laboratory of Functional Genomics and Molecular Diagnosis, Lanzhou University, Lanzhou, China
- Cuiying Biomedical Research Centre, Lanzhou University Second Hospital, Lanzhou, China
| | - Naeem Ullah
- School of Life Sciences, Lanzhou University, Lanzhou, China
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, Lanzhou University, Lanzhou, China
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou, China
| | - Habib Ullah
- School of Life Sciences, Lanzhou University, Lanzhou, China
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, Lanzhou University, Lanzhou, China
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou, China
- Cuiying Biomedical Research Centre, Lanzhou University Second Hospital, Lanzhou, China
| | - Syed Rafiq Hussain Shah
- Department of Microecology, School of Basic Medical Sciences, Dalian Medical University, Dalian, China
| | - Hui Sun
- Cuiying Biomedical Research Centre, Lanzhou University Second Hospital, Lanzhou, China
| | - Chunjiang Zhang
- School of Life Sciences, Lanzhou University, Lanzhou, China
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, Lanzhou University, Lanzhou, China
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou, China
- Gansu Key Laboratory of Functional Genomics and Molecular Diagnosis, Lanzhou University, Lanzhou, China
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18
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Liao L, Zhou M, Wang J, Xue X, Deng Y, Zhao X, Peng C, Li Y. Identification of the Antithrombotic Mechanism of Leonurine in Adrenalin Hydrochloride-Induced Thrombosis in Zebrafish via Regulating Oxidative Stress and Coagulation Cascade. Front Pharmacol 2021; 12:742954. [PMID: 34803688 PMCID: PMC8600049 DOI: 10.3389/fphar.2021.742954] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Accepted: 10/20/2021] [Indexed: 01/11/2023] Open
Abstract
Thrombosis is a general pathological phenomenon during severe disturbances to homeostasis, which plays an essential role in cardiovascular and cerebrovascular diseases. Leonurine (LEO), isolated from Leonurus japonicus Houtt, showes a crucial role in anticoagulation and vasodilatation. However, the properties and therapeutic mechanisms of this effect have not yet been systematically elucidated. Therefore, the antithrombotic effect of LEO was investigated in this study. Hematoxylin-Eosin staining was used to detect the thrombosis of zebrafish tail. Fluorescence probe was used to detect the reactive oxygen species. The biochemical indexes related to oxidative stress (lactate dehydrogenase, malondialdehyde, superoxide dismutase and glutathione) and vasodilator factor (endothelin-1 and nitric oxide) were analyzed by specific commercial assay kits. Besides, we detected the expression of related genes (fga, fgb, fgg, pkcα, pkcβ, vwf, f2) and proteins (PI3K, phospho-PI3K, Akt, phospho-Akt, ERK, phospho-ERK FIB) related to the anticoagulation and fibrinolytic system by quantitative reverse transcription and western blot. Beyond that, metabolomic analyses were carried out to identify the expressions of metabolites associated with the anti-thrombosis mechanism of LEO. Our in vivo experimental results showed that LEO could improve the oxidative stress injury, abnormal platelet aggregation and coagulation dysfunction induced by adrenalin hydrochloride. Moreover, LEO restored the modulation of amino acids and inositol metabolites which are reported to alleviate the thrombus formation. Collectively, LEO attenuates adrenalin hydrochloride-induced thrombosis partly via modulating oxidative stress, coagulation cascade and platelet activation and amino acid and inositol metabolites.
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Affiliation(s)
- Li Liao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, China
| | - Mengting Zhou
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, China
| | - Jing Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, China
| | - Xinyan Xue
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, China
| | - Ying Deng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, China
| | - Xingtao Zhao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, China
| | - Yunxia Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Chengdu, China
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Chaihongsa N, Maneesai P, Sangartit W, Potue P, Bunbupha S, Pakdeechote P. Galangin alleviates vascular dysfunction and remodelling through modulation of the TNF-R1, p-NF-κB and VCAM-1 pathways in hypertensive rats. Life Sci 2021; 285:119965. [PMID: 34543638 DOI: 10.1016/j.lfs.2021.119965] [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: 08/03/2021] [Revised: 09/13/2021] [Accepted: 09/14/2021] [Indexed: 11/26/2022]
Abstract
Galangin is a natural flavonoid isolated from ginger, honey and propolis. AIMS To investigate the effect of galangin on blood pressure, vascular changes, sympathoexcitation, oxidative stress and inflammation in rats treated with NG-nitro-l-arginine methyl ester (l-NAME). MATERIALS AND METHODS Male Wistar rats (220-250 g) were given l-NAME (0.5 mg/mL in drinking water) to induce hypertension for 5 weeks. They were treated with vehicle, galangin (30 or 60 mg/kg), or amlodipine (10 mg/kg) for the final two weeks (n = 6/group). KEY FINDINGS Galangin significantly reduced blood pressure and improved the impairment of endothelium-dependent vasodilation in hypertensive rats. Sympathoexcitation, including enhancement of contractile responses to electrical field stimulation, increases in intensity of tyrosine hydroxylase and plasma norepinephrine concentration in hypertensive rats, was attenuated by galangin treatment. Galangin also reduced systemic and vascular oxidative damage and increased plasma nitric oxide levels in the hypertensive groups. Aortic remodelling accompanied by aortic wall hypertrophy and fibrosis observed in hypertensive rats were alleviated by galangin treatment. Furthermore, galangin exhibited an anti-inflammatory effect by suppressing the upregulation of tumour necrosis factor receptor 1 (TNF-R1), phospho-nuclear factor kappa B (p-NF-κB) and vascular cell adhesion protein 1 (VCAM-1) in aortic tissue and reducing plasma tumour necrosis factor alpha (TNF-α) in l-NAME rats. In conclusion, galangin had antihypertensive effects that were relevant to attenuating endothelial dysfunction, sympathoexcitation and vascular remodelling. These effects might be contributed by antioxidant and anti-inflammatory capacities and modulation of the TNF-R1, p-NF-κB and VCAM-1 pathways in hypertensive rats.
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Affiliation(s)
- Nisita Chaihongsa
- Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
| | - Putcharawipa Maneesai
- Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
| | - Weerapon Sangartit
- Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
| | - Prapassorn Potue
- Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
| | - Sarawoot Bunbupha
- Faculty of Medicine, Mahasarakham University, Mahasarakham 44000, Thailand.
| | - Poungrat Pakdeechote
- Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Research Institute for Human High Performance and Health Promotion, Khon Kaen University, Khon Kaen 40002, Thailand.
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Reaction mechanisms relevant to the formation and utilization of [Ru(edta)(NO)] complexes in aqueous media. J Inorg Biochem 2021; 225:111595. [PMID: 34555599 DOI: 10.1016/j.jinorgbio.2021.111595] [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: 07/21/2021] [Revised: 08/13/2021] [Accepted: 08/27/2021] [Indexed: 12/11/2022]
Abstract
The advancement of Ru(edta) complexes (edta4- = ethylenediamineteraacetate) mediated reactions, including NO generation and its utilization, has not been systematically reviewed to date. This review aims to report the research progress that has been made in exploring the application of Ru(edta) complexes in trapping and generation of NO. Furthermore, utilization of the potential of Ru(edta) complexes to mimic NO synthase and nitrite reductase activity, including thermodynamics and kinetics of NO binding to Ru(edta) complexes, their NO scavenging (in vitro), and antitumor activity will be discussed. Also, the role of [Ru(edta)(NO)] in mediating electrochemical reduction of nitrite, S-nitrosylation of biological thiols, and cross-talk between NO and H2S, will be covered. Reports on the NO-related chemistry of Fe(edta) complexes showing similar behavior are contextualized in this review for comparison purposes. The research contributions compiled herein will provide in-depth mechanistic knowledge for understanding the diverse routes pertaining to the formation of the [Ru(edta)(NO)] species, and its role in effecting the aforementioned reactions of biochemical significance.
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21
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Teranishi K. Non-invasive and accurate readout of superoxide anion in biological systems by near-infrared light. Anal Chim Acta 2021; 1179:338827. [PMID: 34535266 DOI: 10.1016/j.aca.2021.338827] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/21/2021] [Accepted: 07/02/2021] [Indexed: 11/19/2022]
Abstract
Infectious and inflammatory diseases involve superoxide anion (O2•-) production. Real-time and non-invasive evaluation of O2•- in intact biological systems has been a significant challenge in biology and medicine. Here, I report that an advanced near-infrared chemiluminescent probe, MCLA-800, enables reliable non-invasive optical readout of O2•-ex vivo and in vivo. MCLA-800 allowed highly selective and sensitive monitoring of O2•- in undiluted human whole blood ex vivo. For the first time, the use of MCLA-800 revealed two reproducible types of O2•- production in response to stimulation by unopsonized zymosan particles of Saccharomyces cerevisiae, that is, slow response (S-type) and fast response (F-type), specific to each individual. O2•- production was synchronized with myeloperoxidase (MPO) activation in the former type but not in the latter. Moreover, as new findings, MCLA-800 chemiluminescence demonstrated that the chemiluminescence intensity-time properties of formyl-methionyl-leucyl-phenylalanine (fMLP)- or phorbol 12-myristate 13-acetate (PMA)-induced O2•- production and MPO activity were independent of S- and F-type zymosan-induced MCLA-800 chemiluminescence whole blood and that PMA-induced MPO activation synchronized with PMA-induced O2•- production in S- and F-type zymosan-induced MCLA-800 chemiluminescence whole blood, but fMLP-induced MPO activation did not synchronize with fMLP-induced O2•- production in both of S- and F-type blood. Furthermore, MCLA-800 spatiotemporally allowed non-invasive and clear in vivo imaging of O2•- in animal models of acute dermatitis and focal arthritis. Therefore, MCLA-800 could be possibly applied in various advanced diagnostic techniques.
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Affiliation(s)
- Katsunori Teranishi
- Graduate School of Bioresources, Mie University, 1577 Kurimamachiya, Tsu, Mie, 514-8507, Japan.
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22
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Abd-Elrazek A, Shapana H, Shukry W, Galilah D. Comparison between Annona squamosa, Annona cherimolia and Annona atemoya ethanolic extracts extenuative impact against oxidative stress, inflammation and apoptosis in rat kidney induced by Ifosfamid. Toxicol Res (Camb) 2021; 10:947-958. [PMID: 34484686 DOI: 10.1093/toxres/tfab078] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 06/20/2021] [Accepted: 07/25/2021] [Indexed: 11/14/2022] Open
Abstract
Up-regulation of NF-kB and depletion of glutathione are acceptable mechanisms of Ifosfamide (IFO) renal toxicity. This investigation elucidates the role of free radicals, inflammatory and apoptotic markers in ifosfamide-induced rentoxicity and the protection of Annona species planted in Egypt (squamosa, cherimolia), and the hybrid between them (atemoya). Annona seeds extracts were prepared and phytochemical analyses were assessed. Rats were injected with saline or with IFO alone or in combination with Annona squamosa or Annona cherimolia or Annona atemoya orally. Biochemical, gene expression, histological and immune-histological examinations were performed. The results demonstrated that IFO elevated creatinine, sodium, magnesium and urea, along with depleted serum potassium and albumin levels. IFO caused a significant reduction in renal GSH, significant increases in renal MDA, and NOx, and up-regulated iNOS. In addition, IFO treatment showed increase mRNA and protein expression of NF-kB, while down-regulated mRNA and protein expression of Bcl-2, and strong immunohistological expression of caspase-3 as well as BAX in kidney tissues. Different Annona seed extracts significantly enhanced the sharpness of renal injury and improved oxidant responses induced by IFO. Annona extracts down-regulated iNOS, NF-kB expressions, as well as, down-regulated caspase-3 and BAX immunohistological expressions, and up-regulated Bcl-2 expression. A. squamosa showed a more pronounced protective effect. Histopathological examination was in accordance with biochemical results. Recent results suggest that Annona species ameliorated the renal toxicity of ifosfamide by down-regulation of NOx, iNOS, NF-kB, BAX, caspase-3 and MDA in addition to up-regulation of GSH and Bcl-2.
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Affiliation(s)
- Areeg Abd-Elrazek
- Department of Physiology, National Organization for Drug Control and Research (NODCAR), 7 Abu Hazem Rd., Al-Haram St.; Madkour Station Pyramids, Giza, Egypt
| | - Hadeer Shapana
- Botany Department, Faculty of Science, Mansoura University, Mansoura, Egypt
| | - Wafaa Shukry
- Botany Department, Faculty of Science, Mansoura University, Mansoura, Egypt
| | - Doaa Galilah
- Botany Department, Faculty of Science, Mansoura University, Mansoura, Egypt
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23
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Wierońska JM, Cieślik P, Kalinowski L. Nitric Oxide-Dependent Pathways as Critical Factors in the Consequences and Recovery after Brain Ischemic Hypoxia. Biomolecules 2021; 11:biom11081097. [PMID: 34439764 PMCID: PMC8392725 DOI: 10.3390/biom11081097] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/17/2021] [Accepted: 07/20/2021] [Indexed: 12/14/2022] Open
Abstract
Brain ischemia is one of the leading causes of disability and mortality worldwide. Nitric oxide (NO•), a molecule that is involved in the regulation of proper blood flow, vasodilation, neuronal and glial activity constitutes the crucial factor that contributes to the development of pathological changes after stroke. One of the early consequences of a sudden interruption in the cerebral blood flow is the massive production of reactive oxygen and nitrogen species (ROS/RNS) in neurons due to NO• synthase uncoupling, which leads to neurotoxicity. Progression of apoptotic or necrotic neuronal damage activates reactive astrocytes and attracts microglia or lymphocytes to migrate to place of inflammation. Those inflammatory cells start to produce large amounts of inflammatory proteins, including pathological, inducible form of NOS (iNOS), which generates nitrosative stress that further contributes to brain tissue damage, forming vicious circle of detrimental processes in the late stage of ischemia. S-nitrosylation, hypoxia-inducible factor 1α (HIF-1α) and HIF-1α-dependent genes activated in reactive astrocytes play essential roles in this process. The review summarizes the roles of NO•-dependent pathways in the early and late aftermath of stroke and treatments based on the stimulation or inhibition of particular NO• synthases and the stabilization of HIF-1α activity.
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Affiliation(s)
- Joanna M Wierońska
- Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna Street 12, 31-343 Kraków, Poland; (J.M.W.); (P.C.)
| | - Paulina Cieślik
- Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna Street 12, 31-343 Kraków, Poland; (J.M.W.); (P.C.)
| | - Leszek Kalinowski
- Department of Medical Laboratory Diagnostics—Biobank Fahrenheit BBMRI.pl, Medical University of Gdansk, Debinki Street 7, 80-211 Gdansk, Poland
- Biobanking and Biomolecular Resources Research Infrastructure Poland (BBMRI.PL), Debinki Street 7, 80-211 Gdansk, Poland
- BioTechMed Center/Department of Mechanics of Materials and Structures, Gdansk University of Technology, Narutowicza 11/12, 80-223 Gdansk, Poland
- Correspondence: ; Tel.: +48-58-349-1182
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Villar-Martínez MD, Moreno-Ajona D, Chan C, Goadsby PJ. Indomethacin-responsive headaches-A narrative review. Headache 2021; 61:700-714. [PMID: 34105154 DOI: 10.1111/head.14111] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Revised: 03/01/2021] [Accepted: 03/02/2021] [Indexed: 12/22/2022]
Abstract
BACKGROUND Indomethacin is a nonsteroidal anti-inflammatory drug whose mechanism of action in certain types of headache disorders remains unknown. The so-called indomethacin-responsive headache disorders consist of a group of conditions with a very different presentation that have a particularly good response to indomethacin. The response is so distinct as to be used in the definition of two: hemicrania continua and paroxysmal hemicrania. METHODS This is a narrative literature review. PubMed and the Cochrane databases were used for the literature search. RESULTS We review the main pharmacokinetic and pharmacodynamics properties of indomethacin useful for daily practice. The proposed mechanisms of action of indomethacin in the responsive headache disorders, including its effect on cerebral blood flow and intracranial pressure, with special attention to nitrergic mechanisms, are covered. The current evidence for its use in primary headache disorders, such as some trigeminal autonomic cephalalgias, cough, hypnic, exertional or sexual headache, and migraine will be covered, as well as its indication for secondary headaches, such as those of posttraumatic origin. CONCLUSION Increasing understanding of the mechanism(s) of action of indomethacin will enhance our understanding of the complex pathophysiology that might be shared by indomethacin-sensitive headache disorders.
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Affiliation(s)
- Maria Dolores Villar-Martínez
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,Neurology, University of California, Los Angeles, Los Angeles, CA, USA
| | - David Moreno-Ajona
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,Neurology, University of California, Los Angeles, Los Angeles, CA, USA
| | - Calvin Chan
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Peter J Goadsby
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,Neurology, University of California, Los Angeles, Los Angeles, CA, USA
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25
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Cardiovascular and Respiratory Toxicity of Protamine Sulfate in Zebrafish and Rodent Models. Pharmaceutics 2021; 13:pharmaceutics13030359. [PMID: 33803176 PMCID: PMC8001545 DOI: 10.3390/pharmaceutics13030359] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 03/03/2021] [Accepted: 03/05/2021] [Indexed: 11/17/2022] Open
Abstract
Protamine sulfate (PS) is the only available option to reverse the anticoagulant activity of unfractionated heparin (UFH), however it can cause cardiovascular and respiratory complications. We explored the toxicity of PS and its complexes with UFH in zebrafish, rats, and mice. The involvement of nitric oxide (NO) in the above effects was investigated. Concentration-dependent lethality, morphological defects, and decrease in heart rate (HR) were observed in zebrafish larvae. PS affected HR, blood pressure, respiratory rate, peak exhaled CO2, and blood oxygen saturation in rats. We observed hypotension, increase of HR, perfusion of paw vessels, and enhanced respiratory disturbances with increases doses of PS. We found no effects of PS on human hERG channels or signs of heart damage in mice. The hypotension in rats and bradycardia in zebrafish were partially attenuated by the inhibitor of endothelial NO synthase. The disturbances in cardiovascular and respiratory parameters were reduced or delayed when PS was administered together with UFH. The cardiorespiratory toxicity of PS seems to be charge-dependent and involves enhanced release of NO. PS administered at appropriate doses and ratios with UFH should not cause permanent damage of heart tissue, although careful monitoring of cardiorespiratory parameters is necessary.
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Xue J, Shi K, Chen C, Bai Y, Cui Q, Li N, Fu X, Qiao Y. Evaluation of response of dynamics change in bioaugmentation process in diesel-polluted seawater via high-throughput sequencing: Degradation characteristic, community structure, functional genes. JOURNAL OF HAZARDOUS MATERIALS 2021; 403:123569. [PMID: 32798793 DOI: 10.1016/j.jhazmat.2020.123569] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 07/07/2020] [Accepted: 07/21/2020] [Indexed: 06/11/2023]
Abstract
Identification of microorganisms that contribute to the whole microbial community is important. In this study, dynamic changes in bioaugmentation process in diesel-polluted seawater collected from two different sites were assessed via simulation experiments. Ultraviolet spectrophotometry and analysis using the molecular operating environment software revealed that the degradation rate of diesel due to bioaugmentation was higher than 70 % after 45 days because of the formation of hydrogen bonds among biosurfactants and diesel components. Community structure and functional genes were analysed via high-throughput sequencing. Results showed that community diversity recovered during bioaugmentation. Principal coordinate analysis showed that the difference in microbial community between the two sites was considerably smaller than that when diesel was added and bioaugmentation was conducted. After bioaugmentation, the main families playing key roles in degradation that became dominant were Alcanivoracaceae, Rhodobiaceae, and Rhodospirillaceae. Moreover, the abundance of functional genes remarkably increased at two different sites.
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Affiliation(s)
- Jianliang Xue
- College of Safety and Environmental Engineering, Shandong University of Science and Technology, Qingdao, Shandong, 266590, China.
| | - Ke Shi
- College of Safety and Environmental Engineering, Shandong University of Science and Technology, Qingdao, Shandong, 266590, China
| | - Chuan Chen
- School of Environment, Harbin Institute of Technology, Haerbin, Heilongjiang, 150001, China
| | - Yu Bai
- Chinaunicom System Integration Co., Ltd, No.131, Xidan North Road, Beijing, 100085, China
| | - Qinqin Cui
- School of Architecture and Engineering, Qingdao Binhai University, Qingdao, Shandong, 266555, China
| | - Nana Li
- College of Safety and Environmental Engineering, Shandong University of Science and Technology, Qingdao, Shandong, 266590, China
| | - Xinge Fu
- College of Safety and Environmental Engineering, Shandong University of Science and Technology, Qingdao, Shandong, 266590, China
| | - Yanlu Qiao
- College of Safety and Environmental Engineering, Shandong University of Science and Technology, Qingdao, Shandong, 266590, China.
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27
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Yang P, Zhao X, Zhou L, Jin Y, Zheng X, Ouyang Y, Chen M, Zeng L, Chen S, Chen X, Tian Z. Protective effect of oral histidine on hypertension in Dahl salt-sensitive rats induced by high-salt diet. Life Sci 2021; 270:119134. [PMID: 33513395 DOI: 10.1016/j.lfs.2021.119134] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/15/2021] [Accepted: 01/15/2021] [Indexed: 01/11/2023]
Abstract
AIMS Salt-sensitive hypertension is a risk factor for cardiovascular disease. Previous studies have shown that insufficient arginine in the kidney caused by metabolic imbalance is an important factor in salt-sensitive hypertension. Whether the high nitrogen content of histidine can affect the balance of nitrogen metabolism in Dahl salt-sensitive (SS) rats. This article aimed to study the effects of oral histidine on salt-sensitive hypertension, kidney damage and metabolic patterns of high-salt diet in SS rats. MAIN METHODS Adult rats were divided into four groups, and blood pressure was measured using a non-invasive tail-cuff system. Gas chromatography-mass spectrometry analyzed metabolites in serum and kidney tissues. KEY FINDINGS High-salt diet significantly increased the blood pressure of rats and aggravated kidney damage. Of note, histidine can attenuate salt-sensitive hypertension and kidney damage by improving metabolic pattern, reducing Reactive Oxygen Species (ROS) and increasing nitric oxide levels in SS rats. SIGNIFICANCE These results suggest that histidine could be a potential adjuvant to prevent and control salt-sensitive hypertension.
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Affiliation(s)
- Pengfei Yang
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Xinrui Zhao
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Luxin Zhou
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Yuexin Jin
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Xuewei Zheng
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Yanan Ouyang
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Meng Chen
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Li Zeng
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Sa Chen
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Xiangbo Chen
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China
| | - Zhongmin Tian
- The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
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28
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Hassan AY, Maulood IM, Salihi A. The vasodilatory mechanism of nitric oxide and hydrogen sulfide in the human mesenteric artery in patients with colorectal cancer. Exp Ther Med 2021; 21:214. [PMID: 33500703 DOI: 10.3892/etm.2021.9646] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 08/19/2020] [Indexed: 12/24/2022] Open
Abstract
Recent studies have focused on the role of gasotransmitters in cancer progression and prevention. Therefore, the current study was designed to explore the vasodilator activity of NO and H2S in the human mesenteric arteries of patients with colorectal cancer (CRC) via the activation of K+ channels. A total of two sets of experiments were established for the current investigation. Blood samples from patients with CRC were obtained to detect serum levels of endocan and malondialdehyde (MDA). The role of K+ channels in mediating the vasodilation of the human mesenteric artery in response to sodium nitroprusside (SNP) and sodium disulfide (Na2S) was assessed. The level of serum endocan was indicated to be decreased in patients with CRC compared with healthy individuals, while the level of serum MDA remained unaltered between groups. The arterial rings pre-contracted with norepinephrine were first relaxed by the cumulative addition of increasing concentrations of either SNP (30 nM-30 µM) or (1-6 mM). Maximal relaxation rates were then calculated at 15 min intervals for 60 min. Pre-incubation of arterial rings for 20 min with individual K+ channel blockers was indicated to significantly reduce SNP- and Na2S-induced relaxation at different time points. Pre-treatment of L-nitro-arginine methyl ester did not alter vasodilation that was induced by Na2S. Furthermore, vasodilation of the CRC mesenteric artery was not altered by the synergistic application of SNP and Na2S, while pre-incubation of arterial rings with D,L-propargylglycine significantly enhanced vasodilation induced by SNP. These results indicated that endothelial dysfunction and oxidative stress do not serve roles in the pathogenesis of CRC. The dilatory mechanisms of NO and H2S in mesenteric arteries of patients with CRC were K+ channel- and time-dependent, and the activity of cystathionine γ-lyase enzyme inhibited the ability of exogenous NO in vasodilation processes.
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Affiliation(s)
- Awat Y Hassan
- Department of Biology, College of Science, Salahaddin University-Erbil, Erbil, Kurdistan Region 44001, Iraq
| | - Ismail M Maulood
- Department of Biology, College of Science, Salahaddin University-Erbil, Erbil, Kurdistan Region 44001, Iraq
| | - Abbas Salihi
- Department of Biology, College of Science, Salahaddin University-Erbil, Erbil, Kurdistan Region 44001, Iraq.,Department of Medical Analysis, Faculty of Science, Tishk International University, Erbil, Kurdistan Region 44001, Iraq
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Epigenetic Regulation of Pulmonary Arterial Hypertension-Induced Vascular and Right Ventricular Remodeling: New Opportunities? Int J Mol Sci 2020; 21:ijms21238901. [PMID: 33255338 PMCID: PMC7727715 DOI: 10.3390/ijms21238901] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 11/19/2020] [Accepted: 11/20/2020] [Indexed: 12/11/2022] Open
Abstract
Pulmonary artery hypertension (PAH) is a rare chronic disease with high impact on patients’ quality of life and currently no available cure. PAH is characterized by constant remodeling of the pulmonary artery by increased proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), fibroblasts (FBs) and endothelial cells (ECs). This remodeling eventually leads to increased pressure in the right ventricle (RV) and subsequent right ventricle hypertrophy (RVH) which, when left untreated, progresses into right ventricle failure (RVF). PAH can not only originate from heritable mutations, but also develop as a consequence of congenital heart disease, exposure to drugs or toxins, HIV, connective tissue disease or be idiopathic. While much attention was drawn into investigating and developing therapies related to the most well understood signaling pathways in PAH, in the last decade, a shift towards understanding the epigenetic mechanisms driving the disease occurred. In this review, we reflect on the different epigenetic regulatory factors that are associated with the pathology of RV remodeling, and on their relevance towards a better understanding of the disease and subsequently, the development of new and more efficient therapeutic strategies.
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Abstract
Heart failure (HF) is a common consequence of several cardiovascular diseases and is understood as a vicious cycle of cardiac and hemodynamic decline. The current inventory of treatments either alleviates the pathophysiological features (eg, cardiac dysfunction, neurohumoral activation, and ventricular remodeling) and/or targets any underlying pathologies (eg, hypertension and myocardial infarction). Yet, since these do not provide a cure, the morbidity and mortality associated with HF remains high. Therefore, the disease constitutes an unmet medical need, and novel therapies are desperately needed. Cyclic guanosine-3',5'-monophosphate (cGMP), synthesized by nitric oxide (NO)- and natriuretic peptide (NP)-responsive guanylyl cyclase (GC) enzymes, exerts numerous protective effects on cardiac contractility, hypertrophy, fibrosis, and apoptosis. Impaired cGMP signaling, which can occur after GC deactivation and the upregulation of cyclic nucleotide-hydrolyzing phosphodiesterases (PDEs), promotes cardiac dysfunction. In this study, we review the role that NO/cGMP and NP/cGMP signaling plays in HF. After considering disease etiology, the physiological effects of cGMP in the heart are discussed. We then assess the evidence from preclinical models and patients that compromised cGMP signaling contributes to the HF phenotype. Finally, the potential of pharmacologically harnessing cardioprotective cGMP to rectify the present paucity of effective HF treatments is examined.
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31
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Cziráki A, Lenkey Z, Sulyok E, Szokodi I, Koller A. L-Arginine-Nitric Oxide-Asymmetric Dimethylarginine Pathway and the Coronary Circulation: Translation of Basic Science Results to Clinical Practice. Front Pharmacol 2020; 11:569914. [PMID: 33117166 PMCID: PMC7550781 DOI: 10.3389/fphar.2020.569914] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 09/03/2020] [Indexed: 12/16/2022] Open
Abstract
By 1980, it was thought that we already knew most of the major mechanisms regulating vascular tone. However, after the somewhat serendipity discovery that endothelium is involved in mediation of relaxation to acetylcholine, a whole new world opened up and we had to rewrite our concept regarding vascular function and its regulation (not to mention many other fields). The new player was an endothelium derived relaxing factor, which molecular constitution has been identified to be nitric oxide (NO). This review summarizes the major molecular steps concerning how NO is synthetized from L-arginine. Also, the fate of L-arginine is described via the arginase and methylation pathways; both of them are affecting substantially the level and efficacy of NO. In vitro and in vivo effects of L-arginine are summarized and controversial clinical findings are discussed. On the basis of the use of methylated L-arginines, the vasomotor effects of endothelial NO released to agonists and increases in flow/wall shear stress (a major biological stimulus) is summarized. In this review the role of NO in the regulation of coronary vascular resistance, hence blood flow, is delineated and the somewhat questionable clinical use of NO donors is discussed. We made an attempt to summarize the biosynthesis, role, and molecular mechanisms of endogenously produced methylated L-arginine, asymmetric dimethylarginine (ADMA) in modulating vascular resistance, affecting the function of the heart. Additionally, the relationship between ADMA level and various cardiovascular diseases is described, such as atherosclerosis, coronary artery disease (CAD), ischemia/reperfusion injuries, and different types of coronary revascularization. A novel aspect of coronary vasomotor regulation is identified in which the pericardial fluid ADMA and endothelin play putative roles. Finally, some of the open possibilities for future research on L-arginine-NO-ADMA signaling are highlighted.
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Affiliation(s)
- Attila Cziráki
- Medical School, Heart Institute, University of Pécs, Pécs, Hungary.,Szentágothai Research Centre, University of Pécs, Pécs, Hungary
| | - Zsófia Lenkey
- Medical School, Heart Institute, University of Pécs, Pécs, Hungary
| | - Endre Sulyok
- Institute of Public Health and Health Promotion, University of Pécs, Pécs, Hungary
| | - István Szokodi
- Medical School, Heart Institute, University of Pécs, Pécs, Hungary.,Szentágothai Research Centre, University of Pécs, Pécs, Hungary
| | - Akos Koller
- Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary.,Research Center for Sports Physiology, University of Physical Education, Budapest, Hungary.,Department of Physiology, New York Medical College, Valhalla, NY, United States
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32
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Satoh H, Akiba Y, Urushidani T. Proton Pump Inhibitors Prevent Gastric Antral Ulcers Induced by NSAIDs via Activation of Capsaicin-Sensitive Afferent Nerves in Mice. Dig Dis Sci 2020; 65:2580-2594. [PMID: 32140944 DOI: 10.1007/s10620-020-06157-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2019] [Accepted: 02/18/2020] [Indexed: 12/09/2022]
Abstract
BACKGROUND/AIMS We examined the effects of proton pump inhibitors (PPIs) on gastric antral ulcers induced by non-steroidal anti-inflammatory drugs in re-fed mice and the role of capsaicin-sensitive afferent nerves (CSANs) in the protective effects of PPIs on the antral mucosa. METHODS Male mice were administered indomethacin after 2 h of re-feeding of diet after a 24-h fast, and gastric lesions were examined 24 h after indomethacin dosing. The effects of PPIs (lansoprazole and omeprazole), histamine H2-receptor antagonists (H2-RAs, famotidine, ranitidine), capsaicin and misoprostol on the formation of antral ulcers induced by indomethacin were examined. Functional ablation of CSANs was caused by pretreatment of mice with a high dose of capsaicin. RESULTS Indomethacin produced lesions selectively in the gastric antrum in re-fed conditions. Formation of antral ulcers was not affected by H2-RAs, but inhibited by PPIs, capsaicin and misoprostol. The anti-ulcer effect of lansoprazole was 30 times stronger than that of omeprazole. Antral ulcers induced by indomethacin were markedly aggravated in mice with ablated CSANs. The effects of PPIs and capsaicin on ulcer formation were inhibited by ablation of CSANs, pretreatment with a capsaicin receptor antagonist (capsazepine/ruthenium red) and an inhibitor of nitric oxide synthesis (L-NAME). However, the inhibitory effect of misoprostol was not prevented by the ablation of CSANs or drugs. CONCLUSIONS The results suggested that CSANs play an important role in protection of the antral mucosa and that both lansoprazole and omeprazole are capable of preventing NSAID-induced antral ulcers by activating CSANs.
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Affiliation(s)
- Hiroshi Satoh
- Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe, Kyoto, 610-0395, Japan.
| | - Yasutada Akiba
- Departments of Medicine, School of Medicine, University of California Los Angeles, B114, R217, West LA VAMC, 11301 Wilshire Blvd., Los Angeles, CA, 90025, USA.,Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, CA, 90073, USA
| | - Tetsuro Urushidani
- Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe, Kyoto, 610-0395, Japan
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Light adaptation in the chick retina: Dopamine, nitric oxide, and gap-junction coupling modulate spatiotemporal contrast sensitivity. Exp Eye Res 2020; 195:108026. [PMID: 32246982 DOI: 10.1016/j.exer.2020.108026] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 03/25/2020] [Accepted: 03/26/2020] [Indexed: 11/20/2022]
Abstract
Adaptation to changes in ambient light intensity, in retinal cells and circuits, optimizes visual functions. In the retina, light-adaptation results in changes in light-sensitivity and spatiotemporal tuning of ganglion cells. Under light-adapted conditions, contrast sensitivity (CS) of ganglion cells is a bandpass function of spatial frequency; in contrast, dark-adaptation reduces CS, especially at higher spatial frequencies. In this work, we aimed to understand intrinsic neuromodulatory mechanisms that underlie retinal adaptation to changes in ambient light level. Specifically, we investigated how CS is affected by dopamine (DA), nitric oxide (NO), and modifiers of electrical coupling through gap junctions, under different conditions of adapting illumination. Using the optokinetic response as a behavioral readout of direction-selective ganglion cell activity, we characterized the spatial CS of chicks under high- and low-photopic conditions and how it was regulated by DA, NO, and gap-junction uncouplers. We observed that: (1) DA D2R-family agonists and a donor of NO increased CS tested in low-photopic illumination, as if observed in the high-photopic light; whereas (2) removing their effects using either DA antagonists or NO- synthase inhibitors mimicked low-photopic CS; (3) simulation of high-photopic CS by DA agonists was abolished by NO-synthase inhibitors; and (4) selectively blocking coupling via connexin 35/36-containing gap junctions, using a "designer" mimetic peptide, increased CS, as does strong illumination. We conclude that, in the chicken retina: (1) DA and NO induce changes in spatiotemporal processing, similar to those driven by increasing illumination, (2) DA possibly acts through stimulating NO synthesis, and (3) blockade of coupling via gap junctions containing connexin 35/36 also drives a change in retinal CS functions. As a noninvasive method, the optokinetic response can provide rapid, conditional, and reversible assessment of retinal functions when pharmacological reagents are injected into the vitreous humor. Finally, the chick's large eyes, and the many similarities between their adaptational circuit functions and those in mammals such as the mouse, make them a promising model for future retinal research.
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Dotinga BM, Mintzer JP, Moore JE, Hulscher JBF, Bos AF, Kooi EMW. Maturation of Intestinal Oxygenation: A Review of Mechanisms and Clinical Implications for Preterm Neonates. Front Pediatr 2020; 8:354. [PMID: 32719756 PMCID: PMC7347753 DOI: 10.3389/fped.2020.00354] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 05/28/2020] [Indexed: 12/14/2022] Open
Abstract
Nutrient requirements of preterm neonates may be substantial, to support growth and maturation processes in the presence of challenging post-natal circumstances. This may be accompanied by substantial intestinal oxygen requirements. Preterm neonates may not be able to meet these oxygen requirements, due to a developmental delay in intestinal oxygenation regulation mechanisms. This review summarizes the available literature on post-natal maturation of intestinal oxygenation mechanisms and translates these changes into clinical observations and potential implications for preterm neonates. The different mechanisms that may be involved in regulation of intestinal oxygenation, regardless of post-natal age, are first discussed. The contribution of these mechanisms to intestinal oxygenation regulation is then evaluated in newborn and mature intestine. Finally, the course of clinical observations is used to translate these findings to potential implications for preterm neonates.
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Affiliation(s)
- Baukje M Dotinga
- Division of Neonatology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Jonathan P Mintzer
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Mountainside Medical Center, Montclair, NJ, United States
| | - James E Moore
- Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Connecticut Children's Medical Center, University of Connecticut School of Medicine, Hartford, CT, United States
| | - Jan B F Hulscher
- Division of Pediatric Surgery, Department of Surgery, University Medical Center Groningen, Groningen, Netherlands
| | - Arend F Bos
- Division of Neonatology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Elisabeth M W Kooi
- Division of Neonatology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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Sengupta S, Deb M, Nath R, Prasad Saha S, Bhattacharjee A. Optimization of Ethanol Production using Nitrosative Stress Exposed S.cerevisiae. Cell Biochem Biophys 2019; 78:101-110. [PMID: 31875278 DOI: 10.1007/s12013-019-00897-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Accepted: 12/12/2019] [Indexed: 11/28/2022]
Abstract
S.cerevisiae is an industrially important organism known for its ability to produce ethanol as the demand for ethanol is increasing day by day all over the world, the need to find better and alternative ways to increase ethanol production is also rising. In this work we have proposed such alternative but effective method for producing ethanol by S.cerevisiae. Here, we are reporting for the first time the effect of nitrosative stress on ethanol production. Under in vivo condition, nitrosative stress is marked by the modification of macromolecules in the presence of reactive nitrogen species (RNS). Our result showed that treated cells were more capable for ethanol production compared with untreated cells. Our result also showed enhanced alcohol dehydrogenase activity under stressed condition. Further ethanol production was also optimized by using Response Surface Methodology (RSM) with stressed cells. Further, production of ethanol with immobilized beads of stress affected Saccharomyces cerevisiae was also determined. Overall, the obtained data showed that under nitrosative stress, the maximum ethanol production is 34.4 g/l after 24 h and such higher production was observed even after several cycles of fermentation. This is the first report of this kind showing the relation between nitrosative stress and ethanol production in Saccharomyces cerevisiae which may have important industrial application.
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Affiliation(s)
- Swarnab Sengupta
- Department of Microbiology, University of North Bengal, Siliguri, India
| | - Minakshi Deb
- Department of Microbiology, University of North Bengal, Siliguri, India
| | - Rohan Nath
- Department of Microbiology, University of North Bengal, Siliguri, India
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The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure. Nutrients 2019; 11:nu11071679. [PMID: 31336573 PMCID: PMC6683098 DOI: 10.3390/nu11071679] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Revised: 07/14/2019] [Accepted: 07/19/2019] [Indexed: 12/25/2022] Open
Abstract
Nitric oxide (NO) is a well-known vasodilator produced by the vascular endothelium via the enzyme endothelial nitric oxide synthase (eNOS). The inadequate production of NO has been linked to elevated blood pressure (BP) in both human and animal studies, and might be due to substrate inaccessibility. This review aimed to investigate whether oral administration of the amino acids l-arginine (Arg) and l-citrulline (Cit), which are potential substrates for eNOS, could effectively reduce BP by increasing NO production. Both Arg and Cit are effective at increasing plasma Arg. Cit is approximately twice as potent, which is most likely due to a lower first-pass metabolism. The current data suggest that oral Arg supplementation can lower BP by 5.39/2.66 mmHg, which is an effect that is comparable with diet changes and exercise implementation. The antihypertensive properties of Cit are more questionable, but are likely in the range of 4.1/2.08 to 7.54/3.77 mmHg. The exact mechanism by which Cit and Arg exert their effect is not fully understood, as normal plasma Arg concentration greatly exceeds the Michaelis constant (Km) of eNOS. Thus, elevated plasma Arg concentrations would not be expected to increase endogenous NO production significantly, but have nonetheless been observed in other studies. This phenomenon is known as the "l-arginine paradox".
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Liu T, Zhang M, Mukosera GT, Borchardt D, Li Q, Tipple TE, Ishtiaq Ahmed AS, Power GG, Blood AB. L-NAME releases nitric oxide and potentiates subsequent nitroglycerin-mediated vasodilation. Redox Biol 2019; 26:101238. [PMID: 31200239 PMCID: PMC6565607 DOI: 10.1016/j.redox.2019.101238] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 05/27/2019] [Accepted: 06/02/2019] [Indexed: 12/22/2022] Open
Abstract
L-NG-Nitro arginine methyl ester (L-NAME) has been widely applied for several decades in both basic and clinical research as an antagonist of nitric oxide synthase (NOS). Herein, we show that L-NAME slowly releases NO from its guanidino nitro group. Daily pretreatment of rats with L-NAME potentiated mesenteric vasodilation induced by nitrodilators such as nitroglycerin, but not by NO. Release of NO also occurred with the NOS-inactive enantiomer D-NAME, but not with L-arginine or another NOS inhibitor L-NMMA, consistent with the presence or absence of a nitro group in their structure and their nitrodilator-potentiating effects. Metabolic conversion of the nitro group to NO-related breakdown products was confirmed using isotopically-labeled L-NAME. Consistent with Fenton chemistry, transition metals and reactive oxygen species accelerated the release of NO from L-NAME. Both NO production from L-NAME and its nitrodilator-potentiating effects were augmented under inflammation. NO release by L-NAME can confound its intended NOS-inhibiting effects, possibly by contributing to a putative intracellular NO store in the vasculature.
NOS-inhibitor L-NAME is also a precursor of NO. ROS releases NO from the nitro group of L-NAME via Fenton Chemistry. L-NAME potentates nitrodilator-mediated vasodilation. Nitroglycerin may cause vasodilation via activation of an intracellular NO store.
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Affiliation(s)
- Taiming Liu
- Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, CA, 92354, USA
| | - Meijuan Zhang
- Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, CA, 92354, USA
| | - George T Mukosera
- Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, CA, 92354, USA
| | - Dan Borchardt
- Department of Chemistry, University of California, Riverside, CA, 92521, USA
| | - Qian Li
- Neonatal Redox Biology Laboratory, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Trent E Tipple
- Neonatal Redox Biology Laboratory, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | | | - Gordon G Power
- Lawrence D. Longo Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, 92354, USA
| | - Arlin B Blood
- Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, CA, 92354, USA; Lawrence D. Longo Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, 92354, USA.
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Garthwaite J. NO as a multimodal transmitter in the brain: discovery and current status. Br J Pharmacol 2019; 176:197-211. [PMID: 30399649 PMCID: PMC6295412 DOI: 10.1111/bph.14532] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 10/29/2018] [Accepted: 10/31/2018] [Indexed: 12/13/2022] Open
Abstract
NO operates throughout the brain as an intercellular messenger, initiating its varied physiological effects by activating specialized GC-coupled receptors, resulting in the formation of cGMP. In line with the widespread expression of this pathway, NO participates in numerous different brain functions. This review gives an account of the discovery of NO as a signalling molecule in the brain, experiments that originated in the search for a mysterious cGMP-stimulating factor released from central neurones when their NMDA receptors were stimulated, and summarizes the subsequent key steps that helped establish its status as a central transmitter. Currently, various modes of operation are viewed to underlie its diverse behaviour, ranging from very local signalling between synaptic partners (in the orthograde or retrograde directions) to a volume-type transmission whereby NO synthesized by multiple synchronous sources summate spatially and temporally to influence intermingled neuronal or non-neuronal cells, irrespective of anatomical connectivity. LINKED ARTICLES: This article is part of a themed section on Nitric Oxide 20 Years from the 1998 Nobel Prize. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.2/issuetoc.
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Affiliation(s)
- John Garthwaite
- Wolfson Institute for Biomedical ResearchUniversity College LondonLondonUK
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Ma F, Wang R, Zhu J, Zhang Y, Wang Y, Hu W, Bell AE, Liu X. Characterisation comparison of polysaccharides from Dioscorea opposita Thunb. growing in sandy soil, loessial soil and continuous cropping. Int J Biol Macromol 2018; 126:776-785. [PMID: 30599157 DOI: 10.1016/j.ijbiomac.2018.12.259] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Revised: 12/11/2018] [Accepted: 12/28/2018] [Indexed: 11/28/2022]
Abstract
This study compared the characterisations of polysaccharides from Chinese yam (Dioscorea opposita Thunb.) growing in sandy soil (SSCY), loessial soil (LSCY) and second-year continuous cropping (CCCY). SSCY contained the highest total polysaccharides (36.55%) and 80.19% glucose, CCCY from sandy soil obtained 24.55% polysaccharides with 43.66% glucose, whereas LSCY contained 27.54% total polysaccharides and 7.94% glucose. The results indicated that Dioscorea opposita from sandy soil may obtain higher level of glucose. CCCY increased the galacturonic acids in yams from 7.03% to 26.19%, which may have been caused by the decrease in soil pH due to continuous cropping. The starches of SSCY and CCCY from sandy soil belongs to C-type, whereas the starch of LSCY from loessial soil has the A-type pattern. The results suggested that the two types of soil and continuous cropping change the compounds and contents of yams, which provide valuable evidences for cropping management and allelopathy effects.
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Affiliation(s)
- Fanyi Ma
- Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, College of Chemistry and Chemical Engineering, Institute of Environmental and Analytical Sciences, Pharmaceutical College, Henan University, Kaifeng 475004, China
| | - Ruijiao Wang
- Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, College of Chemistry and Chemical Engineering, Institute of Environmental and Analytical Sciences, Pharmaceutical College, Henan University, Kaifeng 475004, China
| | - Jinhua Zhu
- Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, College of Chemistry and Chemical Engineering, Institute of Environmental and Analytical Sciences, Pharmaceutical College, Henan University, Kaifeng 475004, China
| | - Yun Zhang
- Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, College of Chemistry and Chemical Engineering, Institute of Environmental and Analytical Sciences, Pharmaceutical College, Henan University, Kaifeng 475004, China
| | - Yong Wang
- Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, College of Chemistry and Chemical Engineering, Institute of Environmental and Analytical Sciences, Pharmaceutical College, Henan University, Kaifeng 475004, China
| | - Weiping Hu
- Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, College of Chemistry and Chemical Engineering, Institute of Environmental and Analytical Sciences, Pharmaceutical College, Henan University, Kaifeng 475004, China
| | - Alan E Bell
- Department of Food and Nutritional Science, University of Reading, Whitenights, Reading RG6 6AP, UK
| | - Xiuhua Liu
- Key Laboratory of Natural Medicine and Immune-Engineering of Henan Province, College of Chemistry and Chemical Engineering, Institute of Environmental and Analytical Sciences, Pharmaceutical College, Henan University, Kaifeng 475004, China.
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Nanoparticles in Medicine: A Focus on Vascular Oxidative Stress. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:6231482. [PMID: 30356429 PMCID: PMC6178176 DOI: 10.1155/2018/6231482] [Citation(s) in RCA: 93] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 07/26/2018] [Accepted: 08/19/2018] [Indexed: 01/16/2023]
Abstract
Nanotechnology has had a significant impact on medicine in recent years, its application being referred to as nanomedicine. Nanoparticles have certain properties with biomedical applications; however, in some situations, they have demonstrated cell toxicity, which has caused concern surrounding their clinical use. In this review, we focus on two aspects: first, we summarize the types of nanoparticles according to their chemical composition and the general characteristics of their use in medicine, and second, we review the applications of nanoparticles in vascular alteration, especially in endothelial dysfunction related to oxidative stress. This condition can lead to a reduction in nitric oxide (NO) bioavailability, consequently affecting vascular tone regulation and endothelial dysfunction, which is the first phase in the development of cardiovascular diseases. Therefore, nanoparticles with antioxidant properties may improve vascular dysfunction associated with hypertension, diabetes mellitus, or atherosclerosis.
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Allerton TD, Proctor DN, Stephens JM, Dugas TR, Spielmann G, Irving BA. l-Citrulline Supplementation: Impact on Cardiometabolic Health. Nutrients 2018; 10:nu10070921. [PMID: 30029482 PMCID: PMC6073798 DOI: 10.3390/nu10070921] [Citation(s) in RCA: 116] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Revised: 07/09/2018] [Accepted: 07/16/2018] [Indexed: 12/12/2022] Open
Abstract
Diminished bioavailability of nitric oxide (NO), the gaseous signaling molecule involved in the regulation of numerous vital biological functions, contributes to the development and progression of multiple age- and lifestyle-related diseases. While l-arginine is the precursor for the synthesis of NO by endothelial-nitric oxide synthase (eNOS), oral l-arginine supplementation is largely ineffective at increasing NO synthesis and/or bioavailability for a variety of reasons. l-citrulline, found in high concentrations in watermelon, is a neutral alpha-amino acid formed by enzymes in the mitochondria that also serves as a substrate for recycling l-arginine. Unlike l-arginine, l-citrulline is not quantitatively extracted from the gastrointestinal tract (i.e., enterocytes) or liver and its supplementation is therefore more effective at increasing l-arginine levels and NO synthesis. Supplementation with l-citrulline has shown promise as a blood pressure lowering intervention (both resting and stress-induced) in adults with pre-/hypertension, with pre-clinical (animal) evidence for atherogenic-endothelial protection. Preliminary evidence is also available for l-citrulline-induced benefits to muscle and metabolic health (via vascular and non-vascular pathways) in susceptible/older populations. In this review, we examine the impact of supplementing this important urea cycle intermediate on cardiovascular and metabolic health outcomes and identify future directions for investigating its therapeutic impact on cardiometabolic health.
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Affiliation(s)
| | - David N Proctor
- Department of Kinesiology, Pennsylvania State University, University Park, PA 16802, USA.
| | | | - Tammy R Dugas
- Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
| | - Guillaume Spielmann
- Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
- Department of Kinesiology, Louisiana State University, Baton Rouge, LA 70803, USA.
| | - Brian A Irving
- Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
- Department of Kinesiology, Louisiana State University, Baton Rouge, LA 70803, USA.
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Liang H, Ji K, Ge X, Ren M, Liu B, Xi B, Pan L. Effects of dietary arginine on antioxidant status and immunity involved in AMPK-NO signaling pathway in juvenile blunt snout bream. FISH & SHELLFISH IMMUNOLOGY 2018; 78:69-78. [PMID: 29678792 DOI: 10.1016/j.fsi.2018.04.028] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Revised: 04/16/2018] [Accepted: 04/17/2018] [Indexed: 06/08/2023]
Abstract
The present study assessed the effects of dietary arginine on antioxidant status and immunity involved in AMPK-NO signaling pathway in juvenile blunt snout bream. Fish were fed six practical diets with graded arginine levels ranging from 0.87% to 2.70% for 8 weeks. The results showed that compared with the control group (0.87% dietary arginine level), significantly higher mRNA levels of adenosine monophosphate activated protein kinase (AMPK) and nitric oxide synthetase (NOS), activities of total nitric oxide synthetase (T-NOS) and nitric oxide synthetase (iNOS), and plasma nitric oxide (NO) contents were observed in fish fed with 1.62%-2.70% dietary arginine levels. Significantly higher levels of NOS and iNOS were observed in fish fed with 1.62%-2.70% dietary arginine levels in enzyme-linked immune sorbent assay. At dietary arginine levels of 1.22%-2.70%, the mRNA levels of iNOS were significantly improved. Dietary arginine also significantly influenced plasma interleukin 8 (IL-8) and tumour necrosis factor-α (TNF-α) contents. Furthermore, dietary arginine significantly affected the activity and mRNA level of glutathione peroxidase (GPx), the mRNA levels of pro-inflammatory factor including IL-8 and TNF-α and plasma malondialdehyde (MDA) content. However, total superoxide dismutase (T-SOD) activity, plasma complement component 3 (C3) content, plasma immunoglobulin M (IgM) content, plasma interleukin 1β (IL-1β) content and the mRNA levels of copperzinc superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (Mn-SOD) and IL-1β were not significantly affected by dietary arginine. After Aeromonas hydrophila challenge, the death rate was significantly lowered in fish fed with 1.62%-1.96% dietary arginine levels. Furthermore, the mRNA levels of AMPK, NOS and iNOS, plasma NO content and the activities of T-NOS and iNOS showed an upward trend with increasing dietary arginine levels. Significantly higher levels of NOS and iNOS were observed in fish fed with 1.62%-2.70% dietary arginine levels in enzyme-linked immune sorbent assay. At dietary arginine levels of 1.96%-2.31%, T-SOD activities were significantly improved. Significantly higher GPx activities were observed in fish fed with 1.22%-2.70% dietary arginine levels. At dietary arginine levels of 1.22%-2.31%, the plasma TNF-α and IL-8 contents were significantly decreased. Significantly lower plasma IL-1β contents were observed in fish fed 1.62%-1.96% dietary arginine levels. Dietary arginine significantly influenced the mRNA levels of antioxidant and pro-inflammatory genes including Cu/Zn-SOD, Mn-SOD, GPx, IL-8, TNF-α and IL-1β. Significantly higher plasma C3 contents and significantly lower plasma MDA contents were observed in fish fed with 1.62%-1.96% arginine levels. Furthermore, plasma IgM contents were significantly improved at dietary arginine levels of 1.62%-2.31%. However, high dietary arginine group (2.70%) significantly improved the mRNA levels of pro-inflammatory genes including IL-8, TNF-α and IL-1β and plasma MDA, IL-8, TNF-α and IL-1β contents as compared with optimal dietary arginine levels (1.62% and 1.96%). The present results indicate that optimal arginine level (1.62% and 1.96%) could improve antioxidant capacity, immune response and weaken tissues inflammatory involved in arginine-AMPK-NO signaling pathway, while high arginine level resulted in excessive NO production, leading to increase oxidative stress damage and inflammatory response in juvenile blunt snout bream.
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Affiliation(s)
| | - Ke Ji
- Wuxi Fisheries College, , Wuxi 214081, China
| | - Xianping Ge
- Wuxi Fisheries College, , Wuxi 214081, China; Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China.
| | - Mingchun Ren
- Wuxi Fisheries College, , Wuxi 214081, China; Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China.
| | - Bo Liu
- Wuxi Fisheries College, , Wuxi 214081, China; Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Bingwen Xi
- Wuxi Fisheries College, , Wuxi 214081, China; Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Liangkun Pan
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
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Jurisic A, Jurisic Z, Lefkou E, Pombo J, Girardi G. Pravastatin and-L-arginine combination improves umbilical artery blood flow and neonatal outcomes in dichorionic twin pregnancies through an nitric oxide-dependent vasorelaxant effect. Vascul Pharmacol 2018; 110:64-70. [PMID: 29879462 DOI: 10.1016/j.vph.2018.06.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Revised: 04/25/2018] [Accepted: 06/02/2018] [Indexed: 10/14/2022]
Abstract
The increase in fetal and neonatal morbidity and mortality associated with twin pregnancies correlates with an increased risk of preterm delivery, low birth weight, and intrauterine growth restriction (IUGR). Although the pathogenesis of IUGR is unclear and thus management remains a major challenge, feto-placental blood vessels are compromised, and altered umbilical blood flow is observed. In this pilot observational study we investigated the effects of pravastatin plus l-arginine on umbilical artery (umb art) blood flow. Between 2013 and 2016, five women received daily doses l-arginine and pravastatin when an umb art pulsatility index above limits for gestational age was observed and concerns about selective growth restrictions arose. All patients showed selective absent or reversed end-diastolic umbilical artery Doppler flow (AREDV) associated with increased perinatal mortality. Pravastatin (PRAV) plus l-arginine (l-Arg) treatment diminished umb art resistance significantly and allowed pregnancy to continue. No signs of acidosis or hypoxia, normal cardiotocography tracing, normal fetal movement and fetal weight gain were observed in the twins that showed abnormal umb art Dopplers. All neonates were born around 33 weeks (median 33 weeks, IQR [31.4-33.0]), thus diminishing substantially the chances for any prematurity-associated adverse neonatal outcomes. The infants now show normal growth and development. In in vitro studies, pravastatin induced relaxation of aortic rings. Murine studies identified were performed to investigate the mechanism behind PRAV+L-Arg beneficial effects. A nitric oxide (NO)-dependent synergistic vasorelaxant effect of PRAV+L-Arg was demonstrated using aortic rings. Increased levels of placental NO and increased synthesis of eNOS in placental endothelial cells were observed in mice treated with PRAV+L-Arg compared to untreated mice and mice treated with PRAV- or L-Arg alone. This study suggests that PRAV plus L-Arg might be a good therapeutic option to improve blood flow in umbilical arteries prolonging pregnancy and improving pregnancy outcomes in twins. A RCT should be organized to confirm these results.
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Affiliation(s)
- Aleksandar Jurisic
- University of Belgrade Medical School, Narodni Front University Hospital, Belgrade, Serbia
| | | | | | - Joaquim Pombo
- Division of Women and Children's Health, King's College London, United Kingdom
| | - Guillermina Girardi
- Division of Women and Children's Health, King's College London, United Kingdom.
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Nogueira GB, Punaro GR, Oliveira CS, Maciel FR, Fernandes TO, Lima DY, Rodrigues AM, Mouro MG, Araujo SRR, Higa EMS. N-acetylcysteine protects against diabetic nephropathy through control of oxidative and nitrosative stress by recovery of nitric oxide in rats. Nitric Oxide 2018; 78:22-31. [PMID: 29778909 DOI: 10.1016/j.niox.2018.05.003] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2017] [Revised: 04/30/2018] [Accepted: 05/14/2018] [Indexed: 12/22/2022]
Abstract
The diabetes mellitus (DM) induces several changes, with substantial increase of reactive oxygen species (ROS). The ROS cause damage to systemic and renal microvasculature, which could be one of the mechanisms involved in the development of diabetic nephropathy (DN). The ROS modulate other substances like the nitric oxide (NO), a vasodilator with important role in the renal function. N-acetylcysteine (NAC) is an antioxidant that acts replenishing intracellular cysteine levels, which is essential for glutathione formation. The aim of this study was to evaluate the effect of early or late NAC treatment on oxidative/nitrosative stress in DN progression. All rats were submitted to unilateral nephrectomy and diabetes was induced with streptozotocin. The animals were allocated into six groups: controls that received water (CTL) or NAC (CTL + NAC); diabetic groups that received early or late, water (DM-E; DM-L) or NAC (DM + NAC-E; DM + NAC-L), started on 5th day (early) or 4th week (late) after diabetes induction, during 8 weeks. After NAC treatment, the rats were placed in individual metabolic cages to obtain urine and blood samples for analysis of metabolic profile, renal function, thiobarbituric acid reactive substances (TBARS) and NO. At the end of the protocol, the renal cortex was removed for TBARS, NOS evaluation, antioxidants markers and histology. The DM-E group compared to CTL showed a significant increase in glycemia and proteinuria and impaired renal function; there was a significant increase of TBARS in plasma, urine and renal tissue, and also a significant decrease in plasma NO, which were reverted after early NAC treatment. The eNOS was decreased and iNOS was increased in DM-E vs. CTL, p < 0.05. The early NAC treatment in DM rats reduced proteinuria, creatinine, urea, TBARS and iNOS and, increased creatinine clearance, NO and eNOS, increasing significantly the antioxidant defenses, promoting elevated catalase and glutathione compared to DM-E group, all p < 0.05. The late NAC treatment in diabetic rats vs.DM-E showed reduced proteinuria and TBARS excretion and higher values of creatinine clearance and NO, all statistically significant. Histological analysis of the animals in DM-E or DM-L showed significant tubular changes with degeneration and vacuolization in tubular cells, dilated tubular lumen, intense glycosidic degeneration, and discreet mesangial expansion with interstitial fibrosis area. The DM + NAC-E group showed moderate glycosidic degeneration, however, did not present tubular degeneration or fibrosis. The DM + NAC-L group showed severe glycosidic degeneration, moderate tubular cell degeneration, light and focal dilatation of the tubules, with no fibrosis. Our study showed that NAC protected the diabetic rats against renal injury, probably due to the control of oxidative stress via recovery of the NO bioavailability, showing that early NAC was more effective than late treatment. All these data suggest that NAC may be useful in the adjuvant treatment in a safe way, in the early phase of the disease. Eventually, prolonged treatment, even if it is started later, could change the natural history of the disease, delaying the complications of diabetes in renal tissue.
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Affiliation(s)
- Guilherme B Nogueira
- Nephrology Division, Universidade Federal de Sao Paulo, Sao Paulo, Brazil; Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | - Giovana R Punaro
- Nephrology Division, Universidade Federal de Sao Paulo, Sao Paulo, Brazil; Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.
| | - Clemerson S Oliveira
- Translational Medicine, Universidade Federal de Sao Paulo, Sao Paulo, Brazil; Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | - Fabiane R Maciel
- Translational Medicine, Universidade Federal de Sao Paulo, Sao Paulo, Brazil; Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | - Thamires O Fernandes
- Nephrology Division, Universidade Federal de Sao Paulo, Sao Paulo, Brazil; Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | - Deyse Y Lima
- Translational Medicine, Universidade Federal de Sao Paulo, Sao Paulo, Brazil; Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | - Adelson M Rodrigues
- Nephrology Division, Universidade Federal de Sao Paulo, Sao Paulo, Brazil; Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | - Margaret G Mouro
- Nephrology Division, Universidade Federal de Sao Paulo, Sao Paulo, Brazil; Emergency Division, Universidade Federal de Sao Paulo, Sao Paulo, Brazil; Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
| | | | - Elisa M S Higa
- Nephrology Division, Universidade Federal de Sao Paulo, Sao Paulo, Brazil; Emergency Division, Universidade Federal de Sao Paulo, Sao Paulo, Brazil; Translational Medicine, Universidade Federal de Sao Paulo, Sao Paulo, Brazil; Laboratory of Nitric Oxide and Oxidative Stress, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
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Ersoy B, Eroğlu N, Çetin M, Onur E, Özkol M, Coşkun Ş. Asymmetric dimethylarginine levels and diabetes duration: Relationship with measures of subclinical atherosclerosis and cardiac function in children and adolescents with Type 1 diabetes. Diab Vasc Dis Res 2018; 15:196-203. [PMID: 29498294 DOI: 10.1177/1479164118757921] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
AIMS We aimed to evaluate asymmetric dimethylarginine levels in young patients with Type 1 diabetes mellitus according to diabetes duration and to examine the relationship between these levels and measures of atherosclerosis and myocardial function. MATERIALS AND METHODS In total, 83 patients (8.5-22 years) with Type 1 diabetes mellitus were stratified by diabetes duration: 12-60 months (Group 1, n = 27), >60-120 months (Group 2, n = 29) and >120 months (Group 3, n = 27). Asymmetric dimethylarginine levels were assessed. Carotid intima-media thickness was measured. Myocardial function was assessed by M-mode, conventional Doppler and tissue Doppler echocardiography. RESULTS Asymmetric dimethylarginine level was significantly higher in Group 1, while carotid intima-media thickness was significantly greater in Group 3 ( p < 0.05). Tissue Doppler echocardiography showed the ratio of peak early to peak late diastolic myocardial annular velocity decreased significantly in Groups 2 and 3 with a negative correlation with duration (r: -0.310, p = 0.004) and HBA1c levels (r = -0.391, p < 0.001). Myocardial performance index in all groups and isovolumic relaxation time in Group 3 increased significantly. Asymmetric dimethylarginine levels were negatively correlated with carotid intima-media thickness and isovolumic relaxation time ( p < 0.05). CONCLUSION In contrast to adult diabetics, asymmetric dimethylarginine concentration decreases as diabetes duration increases in young Type 1 diabetic patients and is associated with worsening measures of cardiovascular risk and poorer diastolic function.
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Affiliation(s)
- Betül Ersoy
- 1 Department of Endocrinology of Children, Celal Bayar Universitesi, Manisa, Turkey
| | - Nilgün Eroğlu
- 2 Department of Pediatric Hematology and Oncology, Karadeniz Teknik Universitesi, Trabzon, Turkey
| | - Mecnun Çetin
- 3 Department of Pediatric Cardiology, Celal Bayar Universitesi, Manisa, Turkey
| | - Ece Onur
- 4 Department of Medical Biochemistry, Celal Bayar Universitesi, Manisa, Turkey
| | - Mine Özkol
- 5 Department of Pediatric Radiodiagnostic, Celal Bayar Universitesi, Manisa, Turkey
| | - Şenol Coşkun
- 3 Department of Pediatric Cardiology, Celal Bayar Universitesi, Manisa, Turkey
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An Acute Bout of Aquatic Treadmill Exercise Induces Greater Improvements in Endothelial Function and Postexercise Hypotension Than Land Treadmill Exercise: A Crossover Study. Am J Phys Med Rehabil 2018; 97:578-584. [PMID: 29547447 DOI: 10.1097/phm.0000000000000923] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVE The purpose of the study was to compare acute bouts of aquatic treadmill (ATM) and land treadmill (LTM) exercise on flow-mediated dilation, postexercise blood pressure, plasma nitrate/nitrite, and atrial natriuretic peptide in untrained, prehypertensive men. DESIGN In a counterbalanced, crossover design, 19 untrained, prehypertensive men completed bouts of ATM and LTM on separate days. Flow-mediated dilation was measured pre-exercise and 1-hr postexercise. Blood samples were obtained pre-exercise and immediately postexercise and analyzed for plasma nitrate/nitrite and atrial natriuretic peptide. A magnitude-based inference approach to inference was used for statistical analysis. RESULTS A possible clinically beneficial increase in flow-mediated dilation (1.2%, 90% confidence interval = -0.07% to 2.5%) was observed 1 hr after ATM. In contrast, a possible clinically harmful decrease in flow-mediated dilation (-1.3%, 90% confidence interval = -2.7% to 0.2%) was observed 1 hr after LTM. The magnitude of the postexercise systolic blood pressure reduction was greater after ATM (-4.9, SD = 2.9 mm Hg) than LTM (-2.6, SD = 2.5 mm Hg). Atrial natriuretic peptide increased 34.3 (SD = 47.0%) after ATM and decreased -9.0 (SD = 40.0%) after LTM. CONCLUSIONS An acute bout of ATM induced a more favorable endothelial response and greater postexercise hypotensive response than LTM. These changes were associated with increased atrial natriuretic peptide levels after ATM.
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Zafirovic S, Sudar-Milovanovic E, Obradovic M, Djordjevic J, Jasnic N, Borovic ML, Isenovic ER. Involvement of PI3K, Akt and RhoA in Oestradiol Regulation of Cardiac iNOS Expression. Curr Vasc Pharmacol 2018; 17:307-318. [PMID: 29437011 DOI: 10.2174/1570161116666180212142414] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Revised: 02/06/2018] [Accepted: 02/07/2018] [Indexed: 01/12/2023]
Abstract
BACKGROUND Oestradiol is an important regulatory factor with several positive effects on the cardiovascular (CV) system. We evaluated the molecular mechanism of the in vivo effects of oestradiol on the regulation of cardiac inducible nitric oxide (NO) synthase (iNOS) expression and activity. METHODS Male Wistar rats were treated with oestradiol (40 mg/kg, intraperitoneally) and after 24 h the animals were sacrificed. The concentrations of NO and L-Arginine (L-Arg) were determined spectrophotometrically. For protein expressions of iNOS, p65 subunit of nuclear factor-κB (NFκB-p65), Ras homolog gene family-member A (RhoA), angiotensin II receptor type 1 (AT1R), insulin receptor substrate 1 (IRS-1), p85, p110 and protein kinase B (Akt), Western blot method was used. Coimmunoprecipitation was used for measuring the association of IRS-1 with the p85 subunit of phosphatidylinositol- 3-kinase (PI3K). The expression of iNOS messenger ribonucleic acid (mRNA) was measured with the quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis of the tissue was used to detect localization and expression of iNOS in heart tissue. RESULTS Oestradiol treatment reduced L-Arg concentration (p<0.01), iNOS mRNA (p<0.01) and protein (p<0.001) expression, level of RhoA (p<0.05) and AT1R (p<0.001) protein. In contrast, plasma NO (p<0.05), Akt phosphorylation at Thr308 (p<0.05) and protein level of p85 (p<0.001) increased after oestradiol treatment. CONCLUSION Our results suggest that oestradiol in vivo regulates cardiac iNOS expression via the PI3K/Akt signaling pathway, through attenuation of RhoA and AT1R.
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Affiliation(s)
- Sonja Zafirovic
- Institute of Nuclear Sciences "Vinca", Department of Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia
| | - Emina Sudar-Milovanovic
- Institute of Nuclear Sciences "Vinca", Department of Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia
| | - Milan Obradovic
- Institute of Nuclear Sciences "Vinca", Department of Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia
| | - Jelena Djordjevic
- Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Belgrade, Serbia
| | - Nebojsa Jasnic
- Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Belgrade, Serbia
| | - Milica Labudovic Borovic
- Institute of Histology and Embryology "Aleksandar D. Kostic", Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Esma R Isenovic
- Institute of Nuclear Sciences "Vinca", Department of Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.,Faculty of Stomatology, Pancevo, University Business Academy, Novi Sad, Serbia
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Maji UK, Jana P, Chatterjee M, Karmakar S, Saha A, Ghosh TK. Role of Acetyl Salicylic Acid in Controlling the DOCA-Salt Induced Hypertension in Rats by Stimulating the Synthesis of r-Cortexin in the Kidney. High Blood Press Cardiovasc Prev 2018; 25:79-88. [PMID: 29307050 DOI: 10.1007/s40292-017-0241-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2017] [Accepted: 11/16/2017] [Indexed: 12/19/2022] Open
Abstract
INTRODUCTION Hypertension is a metabolic disease which is caused by vasoconstriction and that results into elevated blood pressure. A chronic hypertensive condition affects and even damages to various systems in the body. Presence of renal cortexin (r-cortexin), an antihypertensive protein, which is released from the kidney cortex controls the blood pressure. The effect of r-cortexin was mediated through nitric oxide (NO), a universal vasodilating agent. AIM In our study, acetyl salicylic acid (aspirin), a well-known activator of the endothelial nitric oxide synthase (eNOS) induced r-cortexin synthesis. METHODS The hypertensive rat model was prepared by injecting deoxy corticosterone acetate (DOCA). Synthesis of r-cortexin was measured by the anti-r-cortexin antibody which was raised in adult white Wister albino rat model. NO level was determined by using methemoglobin method and later confirmed by chemiluminescence method. Change in blood pressure was determined indirectly by using NIBP monitoring system. RESULTS Aspirin increased the r-cortexin expression from 64.36 ± 12.6 nM to 216.7 ± 21.31 nM in DOCA induced hypertensive rats. The mechanism was proved with the findings of increased level of NO from 0.4 to 1.9 µM. The DOCA induced blood pressure was also decreased from 139.39 ± 7.36 mm of Hg to 116.57 ± 6.89 mm of Hg in case of systolic blood pressure and in case of diastolic pressure from 110.41 ± 7 mm of Hg to 86.4 ± 2.76 mm of Hg that are quite approximate. CONCLUSION So, from this study it has been found that aspirin induces the r-cortexin synthesis in kidney cortex through the activation of eNOS in DOCA induced hypertensive rats.
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Affiliation(s)
- Uttam Kumar Maji
- Department of Pathology, IPGME&R, Kolkata, 700020, India
- Department of Pharmacology, UCM, IPGME&R, Kolkata, 700020, India
| | - Pradipta Jana
- Sinha Institute of Medical Science and Technology, Kolkata, 700084, India
| | | | - Sanmay Karmakar
- Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India
| | - Arup Saha
- Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India
| | - Tamal Kanti Ghosh
- Department of Pathology, IPGME&R, Kolkata, 700020, India.
- Department of Health and Family Welfare, Goverment of West Bengal, Kolkata, India.
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Yang XX, Zhang Y, Wong YH, Qian PY. HSP90 regulates larval settlement of the bryozoan Bugula neritina through NO pathway. J Exp Biol 2018; 221:jeb.167478. [DOI: 10.1242/jeb.167478] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 02/19/2018] [Indexed: 12/21/2022]
Abstract
The larvae of many sessile marine invertebrates go through a settlement process, during which the planktonic larvae attach to a substrate and metamorphose into sessile juveniles. Larval attachment and metamorphosis (herein defined as “settlement”) are complex processes mediated by many signaling pathways. Nitric oxide (NO) signaling is one of the pathways that inhibits larval settlement in marine invertebrates across different phyla. NO is synthesized by NO synthase (NOS), which is a client of molecular chaperon heat shock protein 90 (HSP90). In the present study, we provide evidence that NO, a gaseous messenger, regulates larval settlement of B. neritina. By using pharmacological bioassays and western blotting, we demonstrated that NO inhibits larval settlement of B. neritina and that NO signals occur mainly in the sensory organ of swimming larvae. The settlement rate of B. neritina larvae decreased after heat shock treatment. Inhibition of HSP90 induced larval settlement, and attenuated the inhibition of NO donors during larval settlement. In addition, the expression level of both HSP90 and NOS declined upon settlement. These results demonstrate that HSP90 regulates the larval settlement of B. neritina by interacting with the NO pathway.
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Affiliation(s)
- Xiao-Xue Yang
- Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong SAR, P. R. China
| | - Yu Zhang
- Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong SAR, P. R. China
- Guangdong Engineering Research Center for Marine Algal Biotechnology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, P. R. China
| | - Yue-Him Wong
- Department of Biotechnology, Akita Prefectural University, Japan
| | - Pei-Yuan Qian
- Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong SAR, P. R. China
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Avilés-Moreno JR, Berden G, Oomens J, Martínez-Haya B. Guanidinium/ammonium competition and proton transfer in the interaction of the amino acid arginine with the tetracarboxylic 18-crown-6 ionophore. Phys Chem Chem Phys 2018; 20:4067-4073. [DOI: 10.1039/c7cp07975c] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
The binding of arginine by the 18-crown-6 tetracarboxylic ionophore relies on extensive host–guest redistribution of electronic charge and proton transfer.
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Affiliation(s)
- Juan Ramón Avilés-Moreno
- Department of Physical
- Chemical and Natural Systems
- Universidad Pablo de Olavide
- E-41013 Seville
- Spain
| | - Giel Berden
- Radboud University
- Institute for Molecules and Materials
- FELIX Laboratory
- Toernooiveld 7c
- The Netherlands
| | - Jos Oomens
- Radboud University
- Institute for Molecules and Materials
- FELIX Laboratory
- Toernooiveld 7c
- The Netherlands
| | - Bruno Martínez-Haya
- Department of Physical
- Chemical and Natural Systems
- Universidad Pablo de Olavide
- E-41013 Seville
- Spain
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