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1
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Li C, Xu X, Zhao X, Du B. The inconsistent pathogenesis of endometriosis and adenomyosis: insights from endometrial metabolome and microbiome. mSystems 2025; 10:e0020225. [PMID: 40261026 PMCID: PMC12090731 DOI: 10.1128/msystems.00202-25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Accepted: 03/25/2025] [Indexed: 04/24/2025] Open
Abstract
Endometriosis (EM) and adenomyosis (AM) are interrelated gynecological disorders characterized by the aberrant presence of endometrial tissue and are frequently linked with chronic pelvic pain and infertility, yet their pathogenetic mechanisms remain largely unclear. In this cross-sectional study, we analyzed endometrial samples from 244 participants, split into 91 EM patients, 56 AM patients, and 97 healthy controls (HC). We conducted untargeted liquid chromatography-mass spectrometry (LC-MS) and 5R 16S rRNA sequencing to examine endometrial metabolome and microbiome profiles. Additionally, we integrated transcriptomic analysis using nine transcriptomic data sets to investigate the biological basis of these conditions. Metabolomic profiling and 16S rRNA sequencing revealed distinct metabolic and microbial signatures. Specific pathways, including linoleic acid and glycerophospholipid metabolism, show significant alterations in both conditions. Notably, four metabolites, including phosphatidylcholine 40:8 [PC(40:8)], exhibited marked changes in both EM and AM, suggesting shared pathological features. Furthermore, taxonomic analysis identified unique bacterial species associated with each condition, particularly those belonging to the phylum Proteobacteria, which correlated with altered metabolic signatures. Machine learning models demonstrated high predictive accuracy for differentiating between AM, EM, and HC based on metabolic and microbial signatures. Integrative analysis with transcriptomic data highlighted distinct pathways related to immune response and signaling transduction for each condition. Our study provides fresh insights into the pathogenesis of AM and EM through a multi-omic approach, suggesting potential inconsistencies in the underlying pathogenetic mechanisms. IMPORTANCE Existing research highlighted a connection between endometriosis (EM) and adenomyosis (AM), underscoring their overlapping symptoms and potential shared pathophysiological mechanisms. Although the role of microbiota in inflammatory conditions has been acknowledged, comprehensive investigations into the endometrial microbiota in cases of EM and AM have been limited. Previous studies identified distinct microbial communities associated with these conditions; however, they were constrained by small sample sizes and a lack of integrated analyses of microbiota and metabolomics. Furthermore, the ongoing debate over whether EM and AM should be classified as separate diseases or related phenotypes emphasizes the necessity for further exploration of their molecular interactions. Our study uncovers distinct microbial and metabolic signatures associated with each condition, revealing both shared and unique pathways that may contribute to their pathogenesis. Furthermore, the integration of transcriptomic data offers valuable insights into the complex interactions underlying these disorders.
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Affiliation(s)
- Chao Li
- Department of Pathology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xinxin Xu
- Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xiaojie Zhao
- Department of Pathology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Bin Du
- Department of Pathology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China
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2
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Qi P, Jiang X, Wang X, Sheng L, Liang J, Zhang L. Unraveling the pathogenesis and prevention strategies of acute high-altitude illness through gut microecology. NPJ Biofilms Microbiomes 2025; 11:62. [PMID: 40263277 PMCID: PMC12015534 DOI: 10.1038/s41522-025-00701-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 04/08/2025] [Indexed: 04/24/2025] Open
Abstract
High-altitude environments, characterized by hypobaric and hypoxic conditions, induce acute hypoxia, resulting in decreased blood oxygen saturation. This hypoxic stress perturbs gut microecological homeostasis, significantly contributing to the pathogenesis of acute mountain sickness. Consequently, elucidating the mechanisms by which high altitude affects gut homeostasis is crucial for developing effective interventions.
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Affiliation(s)
- Ping Qi
- The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, PR China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, PR China
- Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, PR China
- Precision Medicine Laboratory, the First Hospital of Lanzhou University, Lanzhou, 730000, PR China
| | - Xiansen Jiang
- The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, PR China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, PR China
- Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, PR China
- Precision Medicine Laboratory, the First Hospital of Lanzhou University, Lanzhou, 730000, PR China
| | - Xiaojuan Wang
- The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, PR China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, PR China
- Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, PR China
- Precision Medicine Laboratory, the First Hospital of Lanzhou University, Lanzhou, 730000, PR China
| | - Liang Sheng
- The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, PR China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, PR China
- Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, PR China
- Precision Medicine Laboratory, the First Hospital of Lanzhou University, Lanzhou, 730000, PR China
| | - Jiawen Liang
- The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, PR China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, PR China
- Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, PR China
- Precision Medicine Laboratory, the First Hospital of Lanzhou University, Lanzhou, 730000, PR China
| | - Lei Zhang
- The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, PR China.
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, PR China.
- Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, PR China.
- Precision Medicine Laboratory, the First Hospital of Lanzhou University, Lanzhou, 730000, PR China.
- Clinical Research Center for General Surgery of Gansu Province, Lanzhou, 730000, PR China.
- Hepatopancreatobiliary Surgery Institute of Gansu Province, Lanzhou, 730000, PR China.
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3
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Cáceres JC, Michellys NG, Greene BL. Nitric Oxide Inhibition of Glycyl Radical Enzymes and Their Activases. J Am Chem Soc 2025; 147:11777-11788. [PMID: 40133071 PMCID: PMC11987019 DOI: 10.1021/jacs.4c14786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 01/06/2025] [Accepted: 03/18/2025] [Indexed: 03/27/2025]
Abstract
Innate immune response cells produce high concentrations of the free radical nitric oxide (NO) in response to pathogen infection. The antimicrobial properties of NO include nonspecific damage to essential biomolecules and specific inactivation of enzymes central to aerobic metabolism. However, the molecular targets of NO in anaerobic metabolism are less understood. Here, we demonstrate that the Escherichia coli glycyl radical enzyme pyruvate formate lyase (PFL), which catalyzes the anaerobic metabolism of pyruvate, is irreversibly inhibited by NO. Using electron paramagnetic resonance and site-directed mutagenesis we show that NO destroys the glycyl radical of PFL. The activation of PFL by its cognate radical S-adenosyl-l-methionine-dependent activating enzyme (PFL-AE) is also inhibited by NO, resulting in the conversion of the essential iron-sulfur cluster to dinitrosyl iron complexes. Whole-cell EPR and metabolic flux analyses of anaerobically growing E. coli show that PFL and PFL-AE are inhibited by physiologically relevant levels of NO in bacterial cell cultures, resulting in diminished growth and a metabolic shift to lactate fermentation. The class III ribonucleotide reductase (RNR) glycyl radical enzyme and its corresponding RNR-AE are also inhibited by NO in a mechanism analogous to those observed in PFL and PFL-AE, which likely contributes to the bacteriostatic effect of NO. Based on the similarities in reactivity of the PFL/RNR and PFL-AE/RNR-AE enzymes with NO, the mechanism of inactivation by NO appears to be general to the respective enzyme classes. The results implicate an immunological role of NO in inhibiting glycyl radical enzyme chemistry in the gut.
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Affiliation(s)
- Juan Carlos Cáceres
- Interdisciplinary
Program in Quantitative Biosciences, University
of California Santa Barbara, Santa Barbara, California 93106, United States
| | - Nathan G. Michellys
- Department
of Chemistry and Biochemistry, University
of California Santa Barbara, Santa
Barbara, California 93106, United States
| | - Brandon L. Greene
- Interdisciplinary
Program in Quantitative Biosciences, University
of California Santa Barbara, Santa Barbara, California 93106, United States
- Department
of Chemistry and Biochemistry, University
of California Santa Barbara, Santa
Barbara, California 93106, United States
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4
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Cáceres JC, Michellys NG, Greene BL. Nitric Oxide Inhibition of Glycyl Radical Enzymes and Their Activases. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.02.23.639758. [PMID: 40060521 PMCID: PMC11888291 DOI: 10.1101/2025.02.23.639758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 03/25/2025]
Abstract
Innate immune response cells produce high concentrations of the free radical nitric oxide (NO) in response to pathogen infection. The antimicrobial properties of NO include non-specific damage to essential biomolecules and specific inactivation of enzymes central to aerobic metabolism. However, the molecular targets of NO in anaerobic metabolism are less understood. Here, we demonstrate that the Escherichia coli glycyl radical enzyme pyruvate formate lyase (PFL), which catalyzes the anaerobic metabolism of pyruvate, is irreversibly inhibited by NO. Using electron paramagnetic resonance and site-directed mutagenesis we show that NO destroys the glycyl radical of PFL. The activation of PFL by its cognate radical S-adenosyl-L-methionine-dependent activating enzyme (PFL-AE) is also inhibited by NO, resulting in the conversion of the essential iron-sulfur cluster to dinitrosyl iron complexes. Whole-cell EPR and metabolic flux analyses of anaerobically growing Escherichia coli show that PFL and PFL-AE are inhibited by physiologically relevant levels of NO in bacterial cell cultures, resulting in diminished growth and a metabolic shift to lactate fermentation. The class III ribonucleotide reductase (RNR) glycyl radical enzyme and its corresponding RNR-AE are also inhibited by NO in a mechanism analogous to those observed in PFL and PFL-AE, which likely contributes to the bacteriostatic effect of NO. Based on the similarities in reactivity of the PFL/RNR and PFL-AE/RNR-AE enzymes with NO, the mechanism of inactivation by NO appears to be general to the respective enzyme classes. The results implicate an immunological role of NO in inhibiting glycyl radical enzyme chemistry in the gut.
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Affiliation(s)
- Juan Carlos Cáceres
- Interdisciplinary Program in Quantitative Biosciences, University of California Santa Barbara, Santa Barbara, CA, 93106 United States
| | - Nathan G. Michellys
- Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, CA, 93106 United States
| | - Brandon L. Greene
- Interdisciplinary Program in Quantitative Biosciences, University of California Santa Barbara, Santa Barbara, CA, 93106 United States
- Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, CA, 93106 United States
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5
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Bakshi J, Mishra KP. Sodium butyrate prevents lipopolysaccharide induced inflammation and restores the expression of tight junction protein in human epithelial Caco-2 cells. Cell Immunol 2025; 408:104912. [PMID: 39729961 DOI: 10.1016/j.cellimm.2024.104912] [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: 09/17/2024] [Revised: 12/13/2024] [Accepted: 12/20/2024] [Indexed: 12/29/2024]
Abstract
The gastrointestinal (GI) tract is susceptible to damage under high altitude hypoxic conditions, leading to gastrointestinal discomfort and intestinal barrier injury. Sodium butyrate, a short-chain fatty acid present as a metabolite in the gut, has emerged as a promising therapeutic agent due to its ability to act as an immunomodulatory agent and restore intestinal barrier integrity. This study aimed to explore the mechanism by which sodium butyrate exhibits anti inflammatory effect on intestinal epithelial cells. In vitro, Caco-2 epithelial cells and RAW 264.7 macrophages were used to investigate the protective role of sodium butyrate on Lipopolysaccharide (LPS) induced inflammation. Cell viability assays demonstrated that 1 mM (110.86 μg/mL) of sodium butyrate did not exhibit cytotoxicity on cells in vitro. Treatment with sodium butyrate suppressed reactive oxygen species levels and TNF-α production in LPS-stimulated macrophages, indicating its efficacy in mitigating inflammatory responses. Western blot analysis revealed that sodium butyrate attenuated the expression of iNOS in RAW 264.7 macrophage cells. Moreover, sodium butyrate also reversed the LPS induced over expression of HIF-1α, NLRP3, IL-1β as well as NF-kB in Caco-2 epithelial cells and also had a suppressive effect on IL-8 secretion after LPS stimulation. Immunocytochemistry demonstrated that sodium butyrate enhanced tight junction protein occludin expression in Caco-2 cells while also restoring the decreased permeability of the Caco-2 monolayer due to LPS. These results indicate that sodium butyrate may influence immune responses by suppressing inflammatory mediators and improving the integrity of the epithelial barrier. Understanding the intricate interactions between gut metabolites and host immune responses may help in the development of innovative therapeutic strategies to alleviate intestinal inflammation in high altitude environments.
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Affiliation(s)
- Jyotsana Bakshi
- Defence Institute of Physiology and Allied Sciences, Delhi 110054, India
| | - K P Mishra
- Defence Institute of Physiology and Allied Sciences, Delhi 110054, India.
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6
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Birmann PT, Sinott A, Zugno GP, Rodrigues RR, Conceição FR, Sousa FSS, Collares T, Seixas FK, Savegnago L. The antidepressant effect of Komagataella pastoris KM 71 H in maternal separation mice model mediated by the microbiota-gut-brain axis. Behav Brain Res 2025; 476:115287. [PMID: 39393682 DOI: 10.1016/j.bbr.2024.115287] [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: 06/06/2024] [Revised: 09/16/2024] [Accepted: 10/08/2024] [Indexed: 10/13/2024]
Abstract
BACKGROUND The intestinal microbiota plays a fundamental role in maintaining host health, especially during childhood, a critical period for its establishment. Early life stress can lead to shifts in gut microbiota composition, thus increasing the risk of major depressive disorder (MDD) in adulthood. The supplementation with probiotics restores intestinal permeability and the health of gut microbial communities, therefore being potential study targets for the treatment of MDD. In this sense, the yeast Komagataella pastoris was reported as a promising probiotic with antidepressant effect. METHODS Hence, the present study aims to investigate this effect in mice submitted to maternal separation (MS) 3 h per day from PND2 to PND14. Adult mice and mothers were treated with K. pastoris KM71H (8 log UFC.g-1/per animal, i.g.) or PBS (500 µl, i.g.) for 14 days. After behavioral tests, the animals were euthanized, followed by hippocampi and intestines removal for biochemical analysis. RESULTS On behavioral tests, K. pastoris KM71H treatment reduced the immobility time in TST of adult mice and increased the grooming activity in splash test of adult mice and mothers induced by MS. The probiotic treatment restored plasma corticosterone levels and glucocorticoid receptor expression in hippocampi, alongside nitrate/nitrite levels and superoxide dismutase activity in intestine, in addition to reducing reactive species levels in both structures. Moreover, it also normalized the fecal pH and water content of feces. CONCLUSION Thus, we conclude that K. pastoris KM71H is a promising therapeutic strategy for the treatment of MDD.
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Affiliation(s)
- Paloma T Birmann
- Neurobiotechnology Research Group, Postgraduate Program in Biotechnology, Technologic Development Center, Federal University of Pelotas, Pelotas, RS, Brazil
| | - Airton Sinott
- Neurobiotechnology Research Group, Postgraduate Program in Biotechnology, Technologic Development Center, Federal University of Pelotas, Pelotas, RS, Brazil
| | - Giuliana P Zugno
- Neurobiotechnology Research Group, Postgraduate Program in Biotechnology, Technologic Development Center, Federal University of Pelotas, Pelotas, RS, Brazil
| | - Rafael R Rodrigues
- Applied Immunology Laboratory, Postgraduate Program in Biotechnology, Technological Development Center, Federal University of Pelotas, Pelotas, RS, Brazil
| | - Fabricio R Conceição
- Applied Immunology Laboratory, Postgraduate Program in Biotechnology, Technological Development Center, Federal University of Pelotas, Pelotas, RS, Brazil
| | - Fernanda S S Sousa
- Molecular and Cellular Oncology Research Group and Functional Genomics Laboratory, Postgraduate Program in Biotechnology, Technological Development Center, Federal University of Pelotas, Pelotas, RS, Brazil
| | - Tiago Collares
- Molecular and Cellular Oncology Research Group and Functional Genomics Laboratory, Postgraduate Program in Biotechnology, Technological Development Center, Federal University of Pelotas, Pelotas, RS, Brazil
| | - Fabiana K Seixas
- Molecular and Cellular Oncology Research Group and Functional Genomics Laboratory, Postgraduate Program in Biotechnology, Technological Development Center, Federal University of Pelotas, Pelotas, RS, Brazil
| | - Lucielli Savegnago
- Neurobiotechnology Research Group, Postgraduate Program in Biotechnology, Technologic Development Center, Federal University of Pelotas, Pelotas, RS, Brazil.
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Archontakis-Barakakis P, Mavridis T, Chlorogiannis DD, Barakakis G, Laou E, Sessler DI, Gkiokas G, Chalkias A. Intestinal oxygen utilisation and cellular adaptation during intestinal ischaemia-reperfusion injury. Clin Transl Med 2025; 15:e70136. [PMID: 39724463 DOI: 10.1002/ctm2.70136] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 11/06/2024] [Accepted: 12/05/2024] [Indexed: 12/28/2024] Open
Abstract
The gastrointestinal tract can be deranged by ailments including sepsis, trauma and haemorrhage. Ischaemic injury provokes a common constellation of microscopic and macroscopic changes that, together with the paradoxical exacerbation of cellular dysfunction and death following restoration of blood flow, are collectively known as ischaemia-reperfusion injury (IRI). Although much of the gastrointestinal tract is normally hypoxemic, intestinal IRI results when there is inadequate oxygen availability due to poor supply (pathological hypoxia) or abnormal tissue oxygen use and metabolism (dysoxia). Intestinal oxygen uptake usually remains constant over a wide range of blood flows and pressures, with cellular function being substantively compromised when ischaemia leads to a >50% decline in intestinal oxygen consumption. Restoration of perfusion and oxygenation provokes additional injury, resulting in mucosal damage and disruption of intestinal barrier function. The primary cellular mechanism for sensing hypoxia and for activating a cascade of cellular responses to mitigate the injury is a family of heterodimer proteins called hypoxia-inducible factors (HIFs). The HIF system is connected to numerous biochemical and immunologic pathways induced by IRI and the concentration of those proteins increases during hypoxia and dysoxia. Activation of the HIF system leads to augmented transcription of specific genes in various types of affected cells, but may also augment apoptotic and inflammatory processes, thus aggravating gut injury. KEY POINTS: During intestinal ischaemia, mitochondrial oxygen uptake is reduced when cellular oxygen partial pressure decreases to below the threshold required to maintain normal oxidative metabolism. Upon reperfusion, intestinal hypoxia may persist because microcirculatory flow remains impaired and/or because available oxygen is consumed by enzymes, intestinal cells and neutrophils.
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Affiliation(s)
| | - Theodoros Mavridis
- Department of Neurology, Tallaght University Hospital (TUH)/The Adelaide and Meath Hospital incorporating the National Children's Hospital (AMNCH), Dublin, Ireland
| | | | - Georgios Barakakis
- Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Eleni Laou
- Department of Anesthesiology, Agia Sophia Children's Hospital, Athens, Greece
| | - Daniel I Sessler
- Center for Outcomes Research and Department of Anesthesiology, UTHealth, Houston, Texas, USA
- Outcomes Research Consortium®, Houston, Texas, USA
| | - George Gkiokas
- Second Department of Surgery, Aretaieion University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Athanasios Chalkias
- Outcomes Research Consortium®, Houston, Texas, USA
- Institute for Translational Medicine and Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Department of Critical Care Medicine, Tzaneio General Hospital, Piraeus, Greece
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8
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Liu J, Chen X, Wang A, Su D. A mitochondria-targeted nitric oxide probe with large Stokes shift for real-time imaging and evaluation of inflammatory bowel disease in situ. Anal Chim Acta 2024; 1332:343372. [PMID: 39580178 DOI: 10.1016/j.aca.2024.343372] [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: 09/01/2024] [Revised: 10/17/2024] [Accepted: 10/23/2024] [Indexed: 11/25/2024]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a prevalent inflammatory disorder, and the abnormal expression of nitric oxide (NO) produced by biocatalysis of iNOS enzyme in mitochondria is directly associated with the occurrence and progression of IBD. Activatable fluorescent probes offer promising tools for early diagnosis of IBD, however, inadequate biodistribution and limited targeting properties of these probes in vivo severely impede accurate diagnosis of IBD and real-time evaluation of inflammatory levels in situ. Therefore, it is necessary to design a highly efficient fluorescent probe towards NO to overcome inadequate biodistribution and achieve accurate diagnosis and evaluation of IBD in situ. RESULTS We designed a highly efficient mitochondria-targeted "turn-on" NIR fluorescent probe Cy-OMe which has excellent targeting properties and imaging ability. The response mechanism is probe Cy-OMe rapidly undergoes N-nitrosation reaction resulting in "turn-on" NIR fluorescence signal when exposed to NO. Cy-OMe exhibits high sensitivity and specificity in detecting NO content in vitro, owing to its large Stokes shift. Furthermore, the probe Cy-OMe not only efficiently targets mitochondria but also enables precise assessment of fluctuations in endogenous NO concertation across various cell types. Importantly, by virtue of large Stokes shift and excellent mitochondrial targeting ability, Cy-OMe has the capability to specifically evaluate dynamic fluctuations of NO in lipopolysaccharide (LPS)-stimulated IBD mouse models in situ and Cy-OMe was achieved high-contrast imaging and precision diagnosis of intestinal inflammation diseases. SIGNIFICANCE Cy-OMe can accurately assess fluctuations in NO levels and show high signal fidelity in the diseased intestine region, which has prospects in the non-invasive diagnosis of intestinal inflammation in vivo. At the same time, it is expected to serve as a potential diagnose platform for investigating the physiological processes underlying NO-related inflammatory diseases and promoting understanding of the pathological functions of NO across diverse inflammatory diseases.
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Affiliation(s)
- Jiatian Liu
- Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, 100124, Beijing, PR China
| | - Xueqian Chen
- Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, 100124, Beijing, PR China
| | - Andong Wang
- Large-scale Instruments and Equipments Sharing Platform, Beijing University of Technology, 100124, Beijing, PR China
| | - Dongdong Su
- Center of Excellence for Environmental Safety and Biological Effects, Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry, Beijing University of Technology, 100124, Beijing, PR China.
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Chang X, Zheng B, Guo Y, Chen Y, Xie J, Shan J, Wang Y, Xue P, Hu X, Hu X, Yu Q. Bound polyphenols in insoluble dietary fiber of navel orange peel modulate LPS-induced intestinal-like co-culture inflammation through CSF2-mediated NF-κB/JAK-STAT pathway. Food Funct 2024; 15:5942-5954. [PMID: 38738974 DOI: 10.1039/d3fo05579e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2024]
Abstract
Our laboratory previously extracted bound polyphenols (BPP) in insoluble dietary fiber from navel orange peel (NOP-IDF), and the aim of this study was to investigate the anti-inflammatory activity and potential molecular mechanisms of BPP by establishing an LPS-induced intestinal-like Caco-2/RAW264.7 co-culture inflammation model. The results demonstrated that BPP reduced the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), as well as the production of pro-inflammatory cytokines, nitric oxide (NO), and reactive oxidative species (ROS) during the inflammatory damage process. Furthermore, BPP alleviated the lipopolysaccharides (LPS)-induced intestinal barrier damage by attenuating the decrease in trans-epithelial electrical resistance (TEER), diamine oxidase (DAO) activity, and intestinal alkaline phosphatase (IAP) activity, as well as the downregulation of ZO-1, Occludin, and Claudin-1 protein expression levels. RNA-seq results on RAW264.7 cells in the co-culture model showed that the NF-κB and JAK-STAT pathways belonged to the most significantly affected signaling pathways in the KEGG analysis, and western blot confirmed that they are essential for the role of BPP in intestinal inflammation. Additionally, overexpression of the granulocyte-macrophage colony-stimulating factor (CSF2) gene triggered abnormal activation of the NF-κB and JAK-STAT pathways and high-level expression of inflammatory factors, while BPP effectively improved this phenomenon. The above results suggested that BPP could inhibit intestinal inflammatory injury and protect intestinal barrier integrity through CSF2-mediated NF-κB and JAK-STAT pathways.
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Affiliation(s)
- Xinxin Chang
- State Key Laboratory of Food Science and Resources, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
| | - Bing Zheng
- State Key Laboratory of Food Science and Resources, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
| | - Yue Guo
- State Key Laboratory of Food Science and Resources, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
| | - Yi Chen
- State Key Laboratory of Food Science and Resources, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
| | - Jianhua Xie
- State Key Laboratory of Food Science and Resources, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
| | - Jialuo Shan
- State Key Laboratory of Food Science and Resources, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
| | - Yudan Wang
- State Key Laboratory of Food Science and Resources, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
| | - Puyou Xue
- State Key Laboratory of Food Science and Resources, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
| | - Xiaoyi Hu
- State Key Laboratory of Food Science and Resources, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
| | - Xiaobo Hu
- State Key Laboratory of Food Science and Resources, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
| | - Qiang Yu
- State Key Laboratory of Food Science and Resources, China-Canada Joint Laboratory of Food Science and Technology (Nanchang), Nanchang University, 235 Nanjing East Road, Nanchang 330047, China.
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10
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Wu Y, Bashir MA, Shao C, Wang H, Zhu J, Huang Q. Astaxanthin targets IL-6 and alleviates the LPS-induced adverse inflammatory response of macrophages. Food Funct 2024; 15:4207-4222. [PMID: 38512055 DOI: 10.1039/d4fo00610k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/22/2024]
Abstract
Numerous natural compounds are recognized for their anti-inflammatory properties attributed to antioxidant effects and the modulation of key inflammatory factors. Among them, astaxanthin (AST), a potent carotenoid antioxidant, remains relatively underexplored regarding its anti-inflammatory mechanisms and specific molecular targets. In this study, human monocytic leukemia cell-derived macrophages (THP-1) were selected as experimental cells, and lipopolysaccharides (LPS) served as inflammatory stimuli. Upon LPS treatment, the oxidative stress was significantly increased, accompanied by remarkable cellular damage. Moreover, LPSs escalated the expression of inflammation-related molecules. Our results demonstrate that AST intervention could effectively alleviate LPS-induced oxidative stress, facilitate cellular repair, and significantly attenuate inflammation. Further exploration of the anti-inflammatory mechanism revealed AST could substantially inhibit NF-κB translocation and activation, and mitigate inflammatory factor production by hindering NF-κB through the antioxidant mechanism. We further confirmed that AST exhibited protective effects against cell damage and reduced the injury from inflammatory cytokines by activating p53 and inhibiting STAT3. In addition, utilizing network pharmacology and in silico calculations based on molecular docking, molecular dynamics simulation, we identified interleukin-6 (IL-6) as a prominent core target of AST anti-inflammation, which was further validated by the RNA interference experiment. This IL-6 binding capacity actually enabled AST to curb the positive feedback loop of inflammatory factors, averting the onset of possible inflammatory storms. Therefore, this study offers a new possibility for the application and development of astaxanthin as a popular dietary supplement of anti-inflammatory or immunomodulatory function.
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Affiliation(s)
- Yahui Wu
- CAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Anhui Key Laboratory of Environmental Toxicology and Pollution Control Technology, Hefei Institute of Intelligent Agriculture, Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
- Science Island Branch of Graduate School, University of Science & Technology of China, Hefei 230026, China
| | - Mona A Bashir
- CAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Anhui Key Laboratory of Environmental Toxicology and Pollution Control Technology, Hefei Institute of Intelligent Agriculture, Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
- Science Island Branch of Graduate School, University of Science & Technology of China, Hefei 230026, China
| | - Changsheng Shao
- High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China
| | - Han Wang
- CAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Anhui Key Laboratory of Environmental Toxicology and Pollution Control Technology, Hefei Institute of Intelligent Agriculture, Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
- Science Island Branch of Graduate School, University of Science & Technology of China, Hefei 230026, China
| | - Jianxia Zhu
- CAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Anhui Key Laboratory of Environmental Toxicology and Pollution Control Technology, Hefei Institute of Intelligent Agriculture, Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
- School of Nursing, Anhui Medical University, Hefei, Anhui 230032, China
| | - Qing Huang
- CAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Anhui Key Laboratory of Environmental Toxicology and Pollution Control Technology, Hefei Institute of Intelligent Agriculture, Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
- Science Island Branch of Graduate School, University of Science & Technology of China, Hefei 230026, China
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11
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Li Y, Zhang X, Tong R, Xu Q, Zhang N, Liao Q, Pan L. Mechanisms of ammonotelism, epithelium damage, cellular apoptosis, and proliferation in gill of Litopenaeus vannamei under NH 4Cl exposure. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2024; 31:15153-15171. [PMID: 38289553 DOI: 10.1007/s11356-024-32111-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 01/17/2024] [Indexed: 02/24/2024]
Abstract
Excessive ammonia-N in coastal environment and aquaculture threatens the health of marine organisms. To explore the mechanism of gill damage induced by ammonia-N, transcriptome of Litopenaeus vannamei 's gill was carried out under 20 mg/L NH4Cl for 0, 6, and 48 h. K-means clustering analysis suggested that ammonia excretion and metabolism-related genes were elevated. GO and KEGG enrichment analysis suggested that glycosyltransferase activity and amino acid metabolism were affected by ammonia. Moreover, histological observation via three staining methods gave clues on the changes of gill after ammonia-N exposure. Increased mucus, hemocyte infiltration, and lifting of the lamellar epithelium suggested that gill epithelium was suffering damage under ammonia-N stress. Meanwhile, the composition of extracellular matrix (ECM) in connective tissue changed. Based on the findings of transcriptomic and histological analysis, we further investigated the molecular mechanism of gill damage under multiple concentrations of NH4Cl (0, 2, 10, 20 mg/L) for multiple timepoints (0, 3, 6, 12, 24, 48, 72 h). First, ammonia excretion was elevated via ion channel, transporter, and exocytosis pathways, but hemolymph ammonia still kept at a high level under 20 mg/L NH4Cl exposure. Second, we focused on glycosaminoglycan metabolism which was related to the dynamics of ECM. It turned out that the degradation and biosynthesis of chondroitin sulfate (CS) were elevated, suggesting that the structure of CS might be destructed under ammonia-N stress and CS played an important role in maintaining gill structure. It was enlightening that the destructions occurred in extracellular regions were vital to gill damage. Third, ammonia-N stress induced a series of cellular responses including enhanced apoptosis, active inflammation, and inhibited proliferation which were closely linked and jointly led to the impairment of gill. Our results provided some insights into the physiological changes induced by ammonia-N and enriched the understandings of gill damage under environmental stress.
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Affiliation(s)
- Yaobing Li
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, People's Republic of China
| | - Xin Zhang
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, People's Republic of China
| | - Ruixue Tong
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, People's Republic of China
| | - Qiuhong Xu
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, People's Republic of China
| | - Ning Zhang
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, People's Republic of China
| | - Qilong Liao
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, People's Republic of China
| | - Luqing Pan
- The Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, People's Republic of China.
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12
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Rana R, Pundir S, Lal UR, Chauhan R, Upadhyay SK, Kumar D. Phytochemistry and biological activity of Erigeron annuus (L.) Pers. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2023; 396:2331-2346. [PMID: 37178275 DOI: 10.1007/s00210-023-02518-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Accepted: 04/29/2023] [Indexed: 05/15/2023]
Abstract
Erigeron annuus L. is a flowering herb of North America, Europe, Asia and Russia. This plant is used as folk medicine in China for the cure of indigestion, enteritis, epidemic hepatitis, haematuria and diabetes. Phytochemical studies showed the presence of 170 bioactive compounds like coumarins, flavonoids, terpenoids, polyacetylenic compounds; γ-pyrone derivatives, sterols and various caffeoylquinic acids derived from the essential oil and organic extracts from its various parts such as aerial parts, roots, leaves, stems and flowers. The pharmacological studies demonstrated various extracts and the compounds of E. annuus to exhibit anti-fungal, anti-atherosclerosis, anti-inflammatory, antidiabetic, phytotoxic, cytoprotective, antiobesity and antioxidant activities. This article covers a critical compendious on geographical distribution, botanical description, phytochemistry, ethnomedicinal uses and pharmacological activities of E. annuus. However, further in-depth studies are needed to determine the medical uses of E. annuus and its chemical constituents, pharmacological activities and clinical applications.
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Affiliation(s)
- Rupali Rana
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Swati Pundir
- School of Pharmaceutical Sciences, Shoolini University, Himachal Pradesh, Solan, 173229, India.
| | - Uma Ranjan Lal
- School of Pharmaceutical Sciences, Shoolini University, Himachal Pradesh, Solan, 173229, India
- Department of Natural Products, National Institute of Pharmaceutical Education and Research, Punjab, 160062, Mohali, India
| | - Raveen Chauhan
- School of Pharmaceutical Sciences, Shoolini University, Himachal Pradesh, Solan, 173229, India
| | | | - Deepak Kumar
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shoolini University, Himachal Pradesh, Solan, 173229, India.
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13
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Kerget F, Kerget B. Can Fractional Exhaled Nitric Oxide (FeNO) Serve as a Clinical Indicator for Patients Hospitalized with Crimean-Congo Hemorrhagic Fever? Jpn J Infect Dis 2023; 76:226-232. [PMID: 37005275 DOI: 10.7883/yoken.jjid.2022.470] [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] [Indexed: 04/03/2023]
Abstract
Crimean-Congo hemorrhagic fever (CCHF), a zoonotic disease spread by infected viruses, can be a significant cause of morbidity and mortality in endemic areas. This prospective study aimed to establish the relationship between fractional exhaled nitric oxide (FeNO) levels and clinical prognosis of CCHF. The study included 85 participants: 55 patients followed up for CCHF from May to August 2022, and 30 healthy controls. FeNO levels were measured upon hospital admission and were 7.6 ± 3.3 parts per billion (ppb) in patients with mild/moderate CCHF, 2.5 ± 2.1 ppb in patients with severe CCHF, and 6.7 ± 1.7 ppb in the healthy control group. There was no statistically significant difference in FeNO levels between the control group and patients with mild/moderate CCHF (P = 0.09), whereas patients with severe CCHF had lower FeNO levels than those in the control group and patients with mild/moderate CCHF (P < 0.001 for both). FeNO measurement may offer a noninvasive and easily applied approach for predicting the clinical course and prognosis of CCHF in the early stages of the disease.
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Affiliation(s)
- Ferhan Kerget
- Department of Infectious Diseases and Clinical Microbiology, Erzurum Regional Training and Research Hospital, University of Health Sciences, Turkey
| | - Buğra Kerget
- Department of Pulmonary Diseases, Faculty of Medicine, Ataturk University, Turkey
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14
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Dull RO, Hahn RG. Hypovolemia with peripheral edema: What is wrong? Crit Care 2023; 27:206. [PMID: 37245039 PMCID: PMC10225095 DOI: 10.1186/s13054-023-04496-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Accepted: 05/18/2023] [Indexed: 05/29/2023] Open
Abstract
Fluid normally exchanges freely between the plasma and interstitial space and is returned primarily via the lymphatic system. This balance can be disturbed by diseases and medications. In inflammatory disease states, such as sepsis, the return flow of fluid from the interstitial space to the plasma seems to be very slow, which promotes the well-known triad of hypovolemia, hypoalbuminemia, and peripheral edema. Similarly, general anesthesia, for example, even without mechanical ventilation, increases accumulation of infused crystalloid fluid in a slowly equilibrating fraction of the extravascular compartment. Herein, we have combined data from fluid kinetic trials with previously unconnected mechanisms of inflammation, interstitial fluid physiology and lymphatic pathology to synthesize a novel explanation for common and clinically relevant examples of circulatory dysregulation. Experimental studies suggest that two key mechanisms contribute to the combination of hypovolemia, hypoalbuminemia and edema; (1) acute lowering of the interstitial pressure by inflammatory mediators such as TNFα, IL-1β, and IL-6 and, (2) nitric oxide-induced inhibition of intrinsic lymphatic pumping.
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Affiliation(s)
- Randal O. Dull
- Department of Anesthesiology, University of Arizona College of Medicine, 1501 N. Campbell Avenue, Suite 4401, PO Box 245114, Tucson, AZ 85724-5114 USA
- Department of Pathology, University of Arizona College of Medicine, Tucson, AZ USA
- Department of Surgery, University of Arizona College of Medicine, Tucson, AZ USA
| | - Robert G. Hahn
- Karolinska Institute at Danderyds Hospital (KIDS), 171 77 Stockholm, Sweden
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15
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Liu X, Bao X, Wang X, Li C, Yang J, Li Z. Time-dependent immune injury induced by short-term exposure to nanoplastics in the Sepia esculenta larvae. FISH & SHELLFISH IMMUNOLOGY 2023; 132:108477. [PMID: 36494033 DOI: 10.1016/j.fsi.2022.108477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 12/01/2022] [Accepted: 12/05/2022] [Indexed: 06/17/2023]
Abstract
Marine organisms are threatened by various environmental contaminants, and nanoplastics (NPs) is one of the most concerned. Studied have shown that NPs has a certain impact on marine organisms, but the specific molecular mechanism is still unclear. At present, researches on the effect of NPs on marine life mostly focus on crustaceans, gastropods, and bivalves. In this study, cephalopod Sepia esculenta larvae were first used to investigate the potential immune response molecular mechanisms caused by PS-NPs (50 nm, 50 mg/L) short-term exposure (4 and 24 h). Through S. esculenta larvae transcriptome profile of gene expression analysis, 548 and 1990 genes showed differential expression at 4 and 24 h after NPs exposure, respectively. GO and KEGG enrichment analysis were performed to find immune related DEGs. Then, the interaction relationship between the immune related DEGs after NPs exposure was known through the constructed protein-protein interaction network. 20 hub genes were found on the base of KEGG pathway numbers involved and protein-protein interaction numbers. This research supply valuable genes for the study of cephalopod immune response caused by NPs, which can help us further uncover the molecular mechanisms of organism against NPs.
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Affiliation(s)
- Xiumei Liu
- College of Life Sciences, Yantai University, Yantai, 264005, PR China
| | - Xiaokai Bao
- School of Agriculture, Ludong University, Yantai, 264025, PR China
| | - Xumin Wang
- College of Life Sciences, Yantai University, Yantai, 264005, PR China
| | - Chengbo Li
- School of Pharmacy, Binzhou Medical University, Yantai, PR China
| | - Jianmin Yang
- School of Agriculture, Ludong University, Yantai, 264025, PR China
| | - Zan Li
- School of Agriculture, Ludong University, Yantai, 264025, PR China.
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16
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Characterization of Bioactive Compounds Having Antioxidant and Anti-Inflammatory Effects of Liliaceae Family Flower Petal Extracts. J Funct Biomater 2022; 13:jfb13040284. [PMID: 36547543 PMCID: PMC9780968 DOI: 10.3390/jfb13040284] [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: 10/20/2022] [Revised: 12/01/2022] [Accepted: 12/05/2022] [Indexed: 12/13/2022] Open
Abstract
Beneficial natural products utilized in cosmetics formulation and pharmaceutical applications are of enormous interest. Lily (Lilium) serves as an essential edible and medicinal plant species with wide classification. Here, we have performed the screening of various extracts that were prepared from flower petals grown from the bulbs of eight Lilium varieties, with a viewpoint to their applicability as a viable source of natural anti-inflammatory and antioxidants agent. Interestingly, our findings indicated that all ethanol and water extracts exhibited a substantially differential spectrum of antioxidant as well as anti-inflammatory properties. Specifically, Serrano showed a close similarity among ethanol and water extracts among all tested lily petal extracts. Therefore, to obtain a detailed analysis of chemical compounds, liquid chromatography-mass spectroscopy was performed in ethanolic and water extracts of Serrano petals. Together, our preliminary results indicated that lily petals extracts used in this study could serve as a basis to develop a potential new whitening agent with powerful antioxidant and anti-inflammatory properties for medicinal, functional food, and cosmetic applications.
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17
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Regulation of nutrient and electrolyte absorption in human organoid-derived intestinal epithelial cell monolayers. Transl Res 2022; 248:22-35. [PMID: 35513245 DOI: 10.1016/j.trsl.2022.04.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 03/29/2022] [Accepted: 04/26/2022] [Indexed: 11/23/2022]
Abstract
Recently developed human intestinal epithelial 3D organoid cultures are a useful cell culture model to study intestinal transport physiology. From these, 2D monolayer cultures can be generated in which apical transporters are exposed to the medium, thereby better facilitating in vitro investigation of intestinal absorption processes. However, whether nutrient and electrolyte absorption can be physiologically regulated in human organoid-derived monolayers has not been determined. Constitutive nitric oxide (cNO) is known to regulate multiple gastrointestinal physiological functions. Previous studies using in vivo and in vitro mammalian animal models indicate that enhanced intracellular cNO differentially regulates the two primary apical Na transporters in small intestinal epithelial cells. Here, we generated human jejunal organoid-derived monolayers to determine whether apical nutrient and electrolyte transporter function is regulated by cNO in human enterocytes. Western blot analysis and immunocytochemical staining showed that organoid-derived 2D cultures express markers of enterocyte differentiation and form intact monolayers of apical-basal polarized epithelial cells. Uptake studies demonstrated that jejunal monolayers exhibit functional activity of Na-glucose cotransporter 1 (SGLT1; SLC5A1) and Na-H exchanger 3 (NHE3; SLC9A3). In response to physiological increases in cNO, the two primary apical Na transporters were differentially regulated in human intestinal organoid-derived monolayers, across multiple human specimens. An increase in cNO stimulated SGLT1, while NHE3 was inhibited. These results are similar to what is seen in vivo and in vitro in different animal intestinal models. Thus, human jejunal organoid-derived monolayers are an ideal in vitro model to better understand how intestinal nutrient absorption is regulated.
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18
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Yu QQ, Zhang H, Guo Y, Han B, Jiang P. The Intestinal Redox System and Its Significance in Chemotherapy-Induced Intestinal Mucositis. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:7255497. [PMID: 35585883 PMCID: PMC9110227 DOI: 10.1155/2022/7255497] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/04/2022] [Accepted: 04/09/2022] [Indexed: 12/12/2022]
Abstract
Chemotherapy-induced intestinal mucositis (CIM) is a significant dose-limiting adverse reaction brought on by the cancer treatment. Multiple studies reported that reactive oxygen species (ROS) is rapidly produced during the initial stages of chemotherapy, when the drugs elicit direct damage to intestinal mucosal cells, which, in turn, results in necrosis, mitochondrial dysfunction, and ROS production. However, the mechanism behind the intestinal redox system-based induction of intestinal mucosal injury and necrosis of CIM is still undetermined. In this article, we summarized relevant information regarding the intestinal redox system, including the composition and regulation of redox enzymes, ROS generation, and its regulation in the intestine. We innovatively proposed the intestinal redox "Tai Chi" theory and revealed its significance in the pathogenesis of CIM. We also conducted an extensive review of the English language-based literatures involving oxidative stress (OS) and its involvement in the pathological mechanisms of CIM. From the date of inception till July 31, 2021, 51 related articles were selected. Based on our analysis of these articles, only five chemotherapeutic drugs, namely, MTX, 5-FU, cisplatin, CPT-11, and oxaliplatin were shown to trigger the ROS-based pathological mechanisms of CIM. We also discussed the redox system-mediated modulation of CIM pathogenesis via elaboration of the relationship between chemotherapeutic drugs and the redox system. It is our belief that this overview of the intestinal redox system and its role in CIM pathogenesis will greatly enhance research direction and improve CIM management in the future.
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Affiliation(s)
- Qing-Qing Yu
- Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China
- Jining First People's Hospital, Jining Medical College, Jining 272000, China
| | - Heng Zhang
- Department of Laboratory, Shandong Daizhuang Hospital, Jining 272051, China
| | - Yujin Guo
- Jining First People's Hospital, Jining Medical College, Jining 272000, China
| | - Baoqin Han
- Laboratory of Biochemistry and Biomedical Materials, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China
- Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266235, China
| | - Pei Jiang
- Jining First People's Hospital, Jining Medical College, Jining 272000, China
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19
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Ouyang J, Sun L, Zeng F, Wu S. Biomarker-activatable probes based on smart AIEgens for fluorescence and optoacoustic imaging. Coord Chem Rev 2022. [DOI: 10.1016/j.ccr.2022.214438] [Citation(s) in RCA: 69] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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20
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Quintanilha MF, Miranda VC, Souza RO, Gallotti B, Cruz C, Santos EA, Alvarez-Leite JI, Jesus LC, Azevedo V, Trindade LM, Cardoso VN, Ferreira E, Carvalho BA, Soares PM, Vieira AT, Nicoli JR, Martins FS. Bifidobacterium longum subsp. longum 51A attenuates intestinal injury against irinotecan-induced mucositis in mice. Life Sci 2022; 289:120243. [DOI: 10.1016/j.lfs.2021.120243] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 12/07/2021] [Accepted: 12/13/2021] [Indexed: 02/07/2023]
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21
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Wijnands KAP, Meesters DM, Vandendriessche B, Briedé JJ, van Eijk HMH, Brouckaert P, Cauwels A, Lamers WH, Poeze M. Microcirculatory Function during Endotoxemia-A Functional Citrulline-Arginine-NO Pathway and NOS3 Complex Is Essential to Maintain the Microcirculation. Int J Mol Sci 2021; 22:ijms222111940. [PMID: 34769369 PMCID: PMC8584871 DOI: 10.3390/ijms222111940] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Revised: 11/01/2021] [Accepted: 11/01/2021] [Indexed: 02/02/2023] Open
Abstract
Competition for the amino acid arginine by endothelial nitric-oxide synthase (NOS3) and (pro-)inflammatory NO-synthase (NOS2) during endotoxemia appears essential in the derangement of the microcirculatory flow. This study investigated the role of NOS2 and NOS3 combined with/without citrulline supplementation on the NO-production and microcirculation during endotoxemia. Wildtype (C57BL6/N background; control; n = 36), Nos2-deficient, (n = 40), Nos3-deficient (n = 39) and Nos2/Nos3-deficient mice (n = 42) received a continuous intravenous LPS infusion alone (200 μg total, 18 h) or combined with L-citrulline (37.5 mg, last 6 h). The intestinal microcirculatory flow was measured by side-stream dark field (SDF)-imaging. The jejunal intracellular NO production was quantified by in vivo NO-spin trapping combined with electron spin-resonance (ESR) spectrometry. Amino-acid concentrations were measured by high-performance liquid chromatography (HPLC). LPS infusion decreased plasma arginine concentration in control and Nos3−/− compared to Nos2−/− mice. Jejunal NO production and the microcirculation were significantly decreased in control and Nos2−/− mice after LPS infusion. No beneficial effects of L-citrulline supplementation on microcirculatory flow were found in Nos3−/− or Nos2−/−/Nos3−/− mice. This study confirms that L-citrulline supplementation enhances de novo arginine synthesis and NO production in mice during endotoxemia with a functional NOS3-enzyme (control and Nos2−/− mice), as this beneficial effect was absent in Nos3−/− or Nos2−/−/Nos3−/− mice.
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Affiliation(s)
- Karolina A. P. Wijnands
- Department of Surgery, NUTRIM School of Nutrition, Translational Research in Metabolism, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands; (D.M.M.); (H.M.H.v.E.); (M.P.)
- Correspondence: ; Tel.: +31-650-513-913
| | - Dennis M. Meesters
- Department of Surgery, NUTRIM School of Nutrition, Translational Research in Metabolism, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands; (D.M.M.); (H.M.H.v.E.); (M.P.)
- Department of Genetics & Cell Biology, NUTRIM School of Nutrition, Translational Research in Metabolism, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands
| | - Benjamin Vandendriessche
- VIB Inflammation Research Center, 9052 Ghent, Belgium; (B.V.); (P.B.); (A.C.)
- Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
- Byteflies, 2600 Antwerp, Belgium
- Department of Electrical, Computer and Systems Engineering, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Jacob J. Briedé
- Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands;
| | - Hans M. H. van Eijk
- Department of Surgery, NUTRIM School of Nutrition, Translational Research in Metabolism, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands; (D.M.M.); (H.M.H.v.E.); (M.P.)
| | - Peter Brouckaert
- VIB Inflammation Research Center, 9052 Ghent, Belgium; (B.V.); (P.B.); (A.C.)
- Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
| | - Anje Cauwels
- VIB Inflammation Research Center, 9052 Ghent, Belgium; (B.V.); (P.B.); (A.C.)
- Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium
- Orionis Biosciences, 9052 Ghent, Belgium
| | - Wouter H. Lamers
- Department of Anatomy & Embryology, NUTRIM School of Nutrition, Translational Research in Metabolism, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands;
| | - Martijn Poeze
- Department of Surgery, NUTRIM School of Nutrition, Translational Research in Metabolism, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands; (D.M.M.); (H.M.H.v.E.); (M.P.)
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22
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David EE, Yameen MA, Igwenyi IO, David CN. Zinc-fortification restores gut nitric oxide without expression of inducible nitric oxide synthase gene in enterotoxigenic E. coli-induced diarrhea in zinc-deficient rats. SCIENTIFIC AFRICAN 2021. [DOI: 10.1016/j.sciaf.2021.e00867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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23
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Yin B, Liu H, Tan B, Dong X, Chi S, Yang Q, Zhang S. Dietary supplementation of β-conglycinin, with or without sodium butyrate on the growth, immune response and intestinal health of hybrid grouper. Sci Rep 2021; 11:17298. [PMID: 34453080 PMCID: PMC8397726 DOI: 10.1038/s41598-021-96693-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 07/31/2021] [Indexed: 12/15/2022] Open
Abstract
We investigated the effects of low and high doses of β-conglycinin and the ameliorative effects of sodium butyrate (based on high-dose β-conglycinin) on the growth performance, serum immunity, distal intestinal histopathology, and gene, protein expression related to intestinal health in hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂). The results revealed that the instantaneous growth rate (IGR) of grouper significantly increased, decreased, and increased in the low-dose β-conglycinin (bL), high-level β-conglycinin (bH) and high-level β-conglycinin plus sodium butyrate (bH-NaB), respectively. The feed coefficient ratio (FCR) was significantly increased in the bH and bH-NaB, serum levels of IFN-γ, IL-1β, and TNF-α were upregulated in the bH. The intestinal diameter/fold height ratio was significantly increased in the bH. Furthermore, there were increases in nitric oxide (NO), total nitric oxide synthase (total NOS), and peroxynitrite anion (ONOO-) in the bH, and decreases in total NOS and ONOO- in the bH-NaB. In the distal intestine, IL-1β and TGF-β1 mRNA levels were downregulated and upregulated, respective in the bL. The mRNA levels of TNF-α and IL-6 were upregulated in the bH, and downregulated in the bH-NaB, respectively. Occludin, claudin3 and ZO-3 mRNA levels were upregulated in the bL, downregulated in the bH and then upregulated in the bH-NaB. No significant differences were observed in the mRNA levels of IFN-γ and jam4. And the p-PI3K p85Tyr458/total PI3K p85 value was significantly increased in the bH and then decreased in the bH-NaB, and the total Akt value was significantly increased in the bH. These indicate β-conglycinin has a regulatory effect on serum immunity and affect distal intestinal development by modulating distal intestinal injury-related parameters. Within the distal intestinal tract, low- and high-dose β-conglycinin differentially affect immune responses and tight junctions in the distal intestine, which eventually manifests as a reduction in growth performance. Supplementing feed with sodium butyrate might represent an effective approach for enhancing serum immunity, and protects the intestines from damage caused by high-dose β-conglycinin.
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Affiliation(s)
- Bin Yin
- Laboratory of Aquatic Animal Nutrition and Feed, Fisheries College, Guangdong Ocean University, Zhanjiang, 524025, People's Republic of China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Centre of Guangdong Province, Zhanjiang, Guangdong, People's Republic of China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, 524025, People's Republic of China
| | - Hongyu Liu
- Laboratory of Aquatic Animal Nutrition and Feed, Fisheries College, Guangdong Ocean University, Zhanjiang, 524025, People's Republic of China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Centre of Guangdong Province, Zhanjiang, Guangdong, People's Republic of China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, 524025, People's Republic of China
| | - Beiping Tan
- Laboratory of Aquatic Animal Nutrition and Feed, Fisheries College, Guangdong Ocean University, Zhanjiang, 524025, People's Republic of China.
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Centre of Guangdong Province, Zhanjiang, Guangdong, People's Republic of China.
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, 524025, People's Republic of China.
| | - Xiaohui Dong
- Laboratory of Aquatic Animal Nutrition and Feed, Fisheries College, Guangdong Ocean University, Zhanjiang, 524025, People's Republic of China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Centre of Guangdong Province, Zhanjiang, Guangdong, People's Republic of China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, 524025, People's Republic of China
| | - Shuyan Chi
- Laboratory of Aquatic Animal Nutrition and Feed, Fisheries College, Guangdong Ocean University, Zhanjiang, 524025, People's Republic of China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Centre of Guangdong Province, Zhanjiang, Guangdong, People's Republic of China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, 524025, People's Republic of China
| | - Qihui Yang
- Laboratory of Aquatic Animal Nutrition and Feed, Fisheries College, Guangdong Ocean University, Zhanjiang, 524025, People's Republic of China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Centre of Guangdong Province, Zhanjiang, Guangdong, People's Republic of China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, 524025, People's Republic of China
| | - Shuang Zhang
- Laboratory of Aquatic Animal Nutrition and Feed, Fisheries College, Guangdong Ocean University, Zhanjiang, 524025, People's Republic of China
- Aquatic Animals Precision Nutrition and High Efficiency Feed Engineering Research Centre of Guangdong Province, Zhanjiang, Guangdong, People's Republic of China
- Key Laboratory of Aquatic, Livestock and Poultry Feed Science and Technology in South China, Ministry of Agriculture, Zhanjiang, 524025, People's Republic of China
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Liu J, Su X, Lu J, Ning J, Lin M, Zhou H. PM 2.5 induces intestinal damage by affecting gut microbiota and metabolites of rats fed a high-carbohydrate diet. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2021; 279:116849. [PMID: 33773181 DOI: 10.1016/j.envpol.2021.116849] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 02/04/2021] [Accepted: 02/23/2021] [Indexed: 06/12/2023]
Abstract
PM2.5 has a major impact on the gastrointestinal system, but the specific mechanism behind this action is not fully understood. Current studies have focused on the relationship between PM2.5 and intestinal flora disorder, while ignoring the important influence of diet on gut microbes. In this study, SD rats were fed either a normal, high-fat, or high-carbohydrate diet for two months and exposed to PM2.5 (7 mg/kg b.w.) by intratracheal instillation. The results showed that the body and kidney weights of the rats in the high-fat diet group were significantly increased relative to those with a normal diet, and changes in the intestinal microbes and metabolites induced by PM2.5 were observed. Rats in the high-carbohydrate diet group had a significant response, and the diversity and richness indices of the flora were reduced (p < 0.05); additionally, intestinal Biffidobacterium and Lactobacillus were enriched, while many endogenous metabolites were found. Some amino acids derivatives and long-chain fatty acids were increased (p < 0.05). Both diet structure and PM2.5 exposure can affect the composition of gut microbiota, and intestinal metabolites may be associated with cell membrane damage when a high-carbohydrate diet interacts with PM2.5. This study considers multiple dietary factors to further supplement the evidence of intestinal damage via PM2.5.
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Affiliation(s)
- Jinhua Liu
- School of Chemistry and Chemical Engineering, Shihezi University, Key Laboratory of Environmental Monitoring and Pollutant Control of Xinjiang Bingtuan, Xinjiang, 832003, China
| | - Xianghui Su
- Department of Endocrinology, Changji Branch, First Affiliated Hospital of Xinjiang Medical University, Xinjiang, 831100, China
| | - Jianjiang Lu
- School of Chemistry and Chemical Engineering, Shihezi University, Key Laboratory of Environmental Monitoring and Pollutant Control of Xinjiang Bingtuan, Xinjiang, 832003, China.
| | - Jianying Ning
- The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832003, China
| | - Meng Lin
- School of Chemistry and Chemical Engineering, Shihezi University, Key Laboratory of Environmental Monitoring and Pollutant Control of Xinjiang Bingtuan, Xinjiang, 832003, China
| | - Hongjuan Zhou
- School of Chemistry and Chemical Engineering, Shihezi University, Key Laboratory of Environmental Monitoring and Pollutant Control of Xinjiang Bingtuan, Xinjiang, 832003, China
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Arthur S, Palaniappan B, Afroz S, Sundaram U. Unique Regulation of Coupled NaCl Absorption by Inducible Nitric Oxide in a Spontaneous SAMP1/YitFc Mouse Model of Chronic Intestinal Inflammation. Inflamm Bowel Dis 2021; 27:1804-1812. [PMID: 34019094 PMCID: PMC8528149 DOI: 10.1093/ibd/izab093] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Indexed: 12/09/2022]
Abstract
In the small intestine, Na:H (NHE3) and Cl:HCO3 (DRA or PAT1) exchangers present in the brush border membrane (BBM) of absorptive villus cells are primarily responsible for the coupled absorption of NaCl, the malabsorption of which causes diarrhea, a common symptom of inflammatory bowel disease (IBD). Inducible nitric oxide (iNO), a known mediator of inflammation, is increased in the mucosa of the chronically inflamed IBD intestine. An SAMP1/YitFc (SAMP1) mouse, a spontaneous model of chronic ileitis very similar to human IBD, was used to study alterations in NaCl absorption. The SAMP1 and control AKR mice were treated with I-N(6)-(1-Iminoethyl)-lysine (L-NIL) to inhibit iNO production, and DRA/PAT1 and NHE3 activities and protein expression were studied. Though Na:H exchange activity was unaffected, Cl:HCO3 activity was significantly decreased in SAMP1 mice due to a reduction in its affinity for Cl, which was reversed by L-NIL treatment. Though DRA and PAT1 expressions were unchanged in all experimental conditions, phosphorylation studies indicated that DRA, not PAT1, is affected in SAMP1. Moreover, the altered phosphorylation levels of DRA was restored by L-NIL treatment. Inducible NO mediates the inhibition of coupled NaCl absorption by decreasing Cl:HCO3 but not Na:H exchange. Specifically, Cl:HCO3 exchanger DRA but not PAT1 is regulated at the level of its phosphorylation by iNO in the chronically inflamed intestine.
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Affiliation(s)
- Subha Arthur
- Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia, USA, United States
| | - Balasubramanian Palaniappan
- Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia, USA, United States
| | - Sheuli Afroz
- Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia, USA, United States
| | - Uma Sundaram
- Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia, USA, United States,Address correspondence to: Uma Sundaram, MD, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, United States. E-mail:
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Huang Y, Xing K, Qiu L, Wu Q, Wei H. Therapeutic implications of functional tea ingredients for ameliorating inflammatory bowel disease: a focused review. Crit Rev Food Sci Nutr 2021; 62:5307-5321. [PMID: 33635174 DOI: 10.1080/10408398.2021.1884532] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic gastro-intestinal disorders of unknown etiology. There are several drugs approved for treating IBD patients with active disease, including first-line use of aminosalicylates, and secondary choices of immunomodulators and other therapies. These medications might manage disease symptoms, but have also shown significant side-effects in IBD patients. Tea is the second largest beverage in the world and its main active ingredients including tea polyphenols, polysaccharides and tea pigments have been shown promising anti-inflammatory and antioxidant properties. In this review, we summarize the influence of different tea varieties including green tea, black tea and dark tea as potential nutritional therapy for preventing and treating IBD, and discuss the mechanisms of tea ingredients involved in the regulation of oxidative stress, inflammation, signaling pathways, and gut microbiota that could benefit for IBD disease management. Our observation directs further basic and clinical investigations on tea polyphenols and their derivatives as novel IBD therapeutic agents.
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Affiliation(s)
- Yina Huang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China
| | - Keyu Xing
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China
| | - Liang Qiu
- Department of Medical Translational Center, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China
| | - Qinglong Wu
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.,Texas Children's Microbiome Center, Texas Children's Hospital, Houston, Texas, USA
| | - Hua Wei
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China
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27
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Zhang H, Xu X, Liu Z, Sun-Waterhouse D, Wang J, Ma C, Waterhouse GIN, Kang W. Effects of edpetiline from Fritillaria on inflammation and oxidative stress induced by LPS stimulation in RAW264.7 macrophages. Acta Biochim Biophys Sin (Shanghai) 2021; 53:229-237. [PMID: 33399208 DOI: 10.1093/abbs/gmaa160] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Indexed: 12/19/2022] Open
Abstract
The dry bulbs of Fritillaria cirrhosa species can help resolve phlegm, soothe cough, clear heat, and moisten the lung, and the main active components responsible for these effect are its alkaloids. However, it is unclear whether or how edpetiline in Fritillaria can inhibit the excessive inflammatory response and oxidative stress. In this research, we aimed to examine this aspect using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages as an inflammatory model. The quantitative real-time polymerase chain reaction and western blot analysis results showed that edpetiline significantly inhibited the content and mRNA expression levels of proinflammatory cytokines (TNF-α and IL-6) in LPS-induced RAW264.7 cells, significantly increased the mRNA expression of IL-4 (anti-inflammatory cytokine), and markedly downregulated the inflammatory mediators inductible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA and protein expression levels. The oxidative stress induced by LPS was also inhibited by edpetiline, as the level of intracellular reactive oxygen species decreased notably. Edpetiline may exert anti-inflammatory and antioxidant effects through inhibiting the phosphorylation of IκB and the nuclear transcription of nuclear transcription factor-κB p65 and decreasing the phosphorylation of p38 and ERK in the mitogen-activated protein kinase signaling pathway, without activating the JNK/mitogen-activated protein kinase signaling pathway. These findings suggest that edpetiline may be a potential therapeutic agent for the prevention or treatment of inflammation- and oxidative stress-related pathophysiological processes and diseases.
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Affiliation(s)
- Hongli Zhang
- National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng 475004, China
| | - Xiaoqing Xu
- National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng 475004, China
| | - Zhenhua Liu
- National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng 475004, China
| | - Dongxiao Sun-Waterhouse
- Joint International Research Laboratory of Food & Medicine Resource Function of Henan Province, Kaifeng 475004, China
- School of Chemical Sciences, University of Auckland, Auckland 1142, New Zealand
| | - Jinmei Wang
- National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng 475004, China
- Functional Food Engineering Technology Research Center of Henan Province, Kaifeng 475004, China
| | - Changyang Ma
- National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng 475004, China
- Functional Food Engineering Technology Research Center of Henan Province, Kaifeng 475004, China
| | - Geoffrey I N Waterhouse
- Joint International Research Laboratory of Food & Medicine Resource Function of Henan Province, Kaifeng 475004, China
- School of Chemical Sciences, University of Auckland, Auckland 1142, New Zealand
| | - Wenyi Kang
- National R & D Center for Edible Fungus Processing Technology, Henan University, Kaifeng 475004, China
- Functional Food Engineering Technology Research Center of Henan Province, Kaifeng 475004, China
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REN CZ, HU WY, LI JC, XIE YH, JIA NN, SHI J, WEI YY, HU TJ. Ethyl acetate fraction of flavonoids from Polygonum hydropiper L. modulates pseudorabies virus-induced inflammation in RAW264.7 cells via the nuclear factor-kappa B and mitogen-activated protein kinase pathways. J Vet Med Sci 2020; 82:1781-1792. [PMID: 32999131 PMCID: PMC7804032 DOI: 10.1292/jvms.20-0263] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Accepted: 08/21/2020] [Indexed: 01/05/2023] Open
Abstract
Pseudorabies virus (PRV) infection leads to severe inflammatory responses and tissue damage, and many natural herbs exhibit protective effects against viral infection by modulating the inflammatory response. An ethyl acetate fraction of flavonoids from Polygonum hydropiper L. (FEA) was prepared through ethanol extraction and ethyl acetate fractional extraction. An inflammatory model was established in RAW264.7 cells with PRV infection to evaluate the anti-inflammatory activity of FEA by measuring cell viability, nitric oxide (NO) production, reactive oxygen species (ROS) release, and mRNA expression of inflammatory factors, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Its functional mechanism was investigated by analyzing the phosphorylation and nuclear translocation of key proteins in the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Our findings indicate that PRV induced inflammatory responses in RAW264.7 cells, and the responses were similar to that in lipopolysaccharide (LPS)-stimulated cells. FEA significantly suppressed NO synthesis and down-regulated both expression and secretion of COX-2, iNOS, and inflammatory cytokines (P<0.05 or P<0.01). FEA also reduced NF-κB p65 translocation into the nucleus and decreased MAPK phosphorylation, indicating that the NF-κB/MAPK signaling pathway may be closely related to the inflammatory response during viral infection. The findings suggested the potential pharmaceutical application of FEA as a natural product that can treat viral infections due to its ability to mitigate inflammatory responses.
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Affiliation(s)
- Chun-Zhi REN
- College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
- Guangxi Agricultural Vocational College, Nanning 530007, PR China
| | - Wen-Yue HU
- School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, 200030, PR China
| | - Jun-Cheng LI
- Guangxi Agricultural Vocational College, Nanning 530007, PR China
| | - Ying-Hong XIE
- College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
| | - Ni-Na JIA
- College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
| | - Jun SHI
- College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
| | - Ying-Yi WEI
- College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
| | - Ting-Jun HU
- College of Animal Science and Technology, Guangxi University, Nanning 530004, PR China
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Yang Y, Li R, Hui J, Li L, Zheng X. β-Carotene attenuates LPS-induced rat intestinal inflammation via modulating autophagy and regulating the JAK2/STAT3 and JNK/p38 MAPK signaling pathways. J Food Biochem 2020; 45:e13544. [PMID: 33147650 DOI: 10.1111/jfbc.13544] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 09/30/2020] [Accepted: 10/07/2020] [Indexed: 02/01/2023]
Abstract
Inflammation is a protective response of the immune defense system and inflammatory response could be regulated by autophagy. β-Carotene has shown anti-inflammatory potential. However, whether β-carotene could alleviate rat intestinal inflammation by modulating autophagy and its anti-inflammation underlying mechanisms remain unknown. In this study, we found that β-carotene significantly reduced (p < .05) the production of nitric oxide (NO), prostaglandin (PG)E2, tumor necrosis factor (TNF)-α, and interleukin-1β (IL-1β) levels by the Griess reaction and enzyme-linked immunosorbent assay (ELISA), and we found that β-carotene significantly suppressed (p < .05) the mRNA expression levels of IL-1β and TNF-α by RT-PCR. In addition, H&E staining revealed that β-carotene could improve intestinal morphology and cell morphology. Furthermore, the levels of signaling proteins of microtubule-associated protein light chain 3 (LC3), AKT, Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3), nuclear factor-kappa B (NF-κB), and c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) were detected by Western blot analysis. We found that β-carotene significantly attenuated (p < .05) the related signaling proteins activated by lipopolysaccharide (LPS) stimulation in rats. Moreover, this conclusion was also verified in intestinal epithelial cell (IEC)-6. 3-Methyladenine (3-MA) is widely used as inhibitor of autophagy via its inhibitory effect on class III PI3K. Simultaneously, pretreatment of 3-MA suppressed the inhibiting effects of β-carotene on the related signaling proteins. This study demonstrates that β-carotene could attenuate the LPS-induced intestinal inflammation in rats via modulating autophagy and regulating the JAK2/STAT3 and JNK/p38 MAPK signaling pathways. We also found the same phenomenon when we verified the results with the IEC-6 cells. These findings provide new insights into improving the nutritional value of basic diets and enhancing immune performance. PRACTICAL APPLICATIONS: β-Carotene is a generally acknowledged natural carotenoid nutrient that exhibits provitamin A activity, and it is widely found in fruits or vegetables. Our study provide a new insight into the anti-inflammatory mechanism of β-carotene. Treatment with β-carotene can be used for the beneficial effect against LPS-induced inflammation damage. This study not only lays the foundation for the related research on the anti-inflammatory properties of β-carotene in vitro and in rat models, but also holds important significance in the field of food.
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Affiliation(s)
- Yu Yang
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
| | - Ruonan Li
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
| | - Junnan Hui
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
| | - Lingqian Li
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
| | - Xin Zheng
- College of Animal Science and Technology, Jilin Agricultural University, Changchun, China
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30
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Inducible Nitric Oxide Regulates Na-Glucose Co-transport in a Spontaneous SAMP1/YitFc Mouse Model of Chronic Ileitis. Nutrients 2020; 12:nu12103116. [PMID: 33065982 PMCID: PMC7600670 DOI: 10.3390/nu12103116] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 09/29/2020] [Accepted: 10/02/2020] [Indexed: 12/30/2022] Open
Abstract
In mammalian small intestine, glucose is primarily absorbed via Na-dependent glucose co-transporter (SGLT1) on the brush border membrane (BBM) of absorptive villus cells. Malabsorption of nutrients (e.g., glucose) leads to malnutrition, a common symptom of inflammatory bowel disease (IBD), where the mucosa is characterized by chronic inflammation. Inducible nitric oxide (iNO) is known to be elevated in IBD mucosa. SAMP1/YitFc (SAMP1) mouse is a spontaneous model of chronic ileitis that develops lesions in its terminal ileum, very similar to human IBD. How SGLT1 may be affected in SAMP1 model of chronic ileitis is unknown. Ten-week-old SAMP1 mice with AKR mice as control were treated with N6-(1-iminoethyl)-L-lysine dihydrochloride (L-NIL) to inhibit iNO production. Intracellular NO levels were found to be increased in villus cells from SAMP1 mice. Moreover, SGLT1 and Na+/K+-ATPase activities and BBM SGLT1 expression were significantly decreased. However, L-NIL treatment reduced the intracellular iNO production, and reversed both downregulated SGLT1 and Na+/K+-ATPase activities in SAMP1 mice. Inhibition of iNO by L-NIL treatment also significantly reversed the BBM SGLT1 protein expression in SAMP1 mice. L-NIL reversed the inflammation mediated downregulation of SGLT1 activity by restoring the BBM SGLT1 expression. Thus, regulation of SGLT1 in chronic ileitis is likely mediated by iNO.
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Beaumont M, Blachier F. Amino Acids in Intestinal Physiology and Health. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1265:1-20. [PMID: 32761567 DOI: 10.1007/978-3-030-45328-2_1] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Dietary protein digestion is an efficient process resulting in the absorption of amino acids by epithelial cells, mainly in the jejunum. Some amino acids are extensively metabolized in enterocytes supporting their high energy demand and/or production of bioactive metabolites such as glutathione or nitric oxide. In contrast, other amino acids are mainly used as building blocks for the intense protein synthesis associated with the rapid epithelium renewal and mucin production. Several amino acids have been shown to support the intestinal barrier function and the intestinal endocrine function. In addition, amino acids are metabolized by the gut microbiota that use them for their own protein synthesis and in catabolic pathways releasing in the intestinal lumen numerous metabolites such as ammonia, hydrogen sulfide, branched-chain amino acids, polyamines, phenolic and indolic compounds. Some of them (e.g. hydrogen sulfide) disrupts epithelial energy metabolism and may participate in mucosal inflammation when present in excess, while others (e.g. indole derivatives) prevent gut barrier dysfunction or regulate enteroendocrine functions. Lastly, some recent data suggest that dietary amino acids might regulate the composition of the gut microbiota, but the relevance for the intestinal health remains to be determined. In summary, amino acid utilization by epithelial cells or by intestinal bacteria appears to play a pivotal regulator role for intestinal homeostasis. Thus, adequate dietary supply of amino acids represents a key determinant of gut health and functions.
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Affiliation(s)
- Martin Beaumont
- GenPhySE, Université de Toulouse, INRA, INPT, ENVT, Toulouse, France
| | - François Blachier
- Université Paris-Saclay, AgroParisTech, INRAE, UMR PNCA, Paris, France.
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Structure-Dependent Effects of Bisphosphonates on Inflammatory Responses in Cultured Neonatal Mouse Calvaria. Antioxidants (Basel) 2020; 9:antiox9060503. [PMID: 32526922 PMCID: PMC7346192 DOI: 10.3390/antiox9060503] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 06/03/2020] [Accepted: 06/04/2020] [Indexed: 12/20/2022] Open
Abstract
Bisphosphonates (BPs) are classified into two groups, according to their side chain structures, as nitrogen-containing BPs (NBPs) and non-nitrogen-containing BPs (non-NBPs). In this study, we examined the effects of NBPs and non-NBPs on inflammatory responses, by quantifying the inflammatory mediators, prostaglandin E2 (PGE2) and nitric oxide (NO), in cultured neonatal mouse calvaria. All examined NBPs (pamidronate, alendronate, incadronate, risedronate, zoledronate) stimulated lipopolysaccharide (LPS)-induced PGE2 and NO production by upregulating COX-2 and iNOS mRNA expression, whereas non-NBPs (etidronate, clodronate, tiludronate) suppressed PGE2 and NO production, by downregulating gene expression. Additionally, [4-(methylthio) phenylthio] methane bisphosphonate (MPMBP), a novel non-NBP with an antioxidant methylthio phenylthio group in its side chain, exhibited the most potent anti-inflammatory activity among non-NBPs. Furthermore, results of immunohistochemistry showed that the nuclear translocation of NF-κB/p65 and tyrosine nitration of cytoplasmic protein were stimulated by zoledronate, while MPMBP inhibited these phenomena, by acting as a superoxide anion (O2−) scavenger. These findings indicate that MPMBP can act as an efficacious agent that causes fewer adverse effects in patients with inflammatory bone diseases, including periodontitis and rheumatoid arthritis.
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Singh S, Arthur S, Sundaram U. Mechanisms of Regulation of Transporters of Amino Acid Absorption in Inflammatory Bowel Diseases. Compr Physiol 2020; 10:673-686. [PMID: 32163200 DOI: 10.1002/cphy.c190016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Intestinal absorption of dietary amino acids/peptides is essential for protein homeostasis, which in turn is crucial for maintaining health as well as restoration of health from significant diseases. Dietary amino acids/peptides are absorbed by unique transporter processes present in the brush border membrane of absorptive villus cells, which line the entire length of the intestine. To date, the only nutrient absorptive system described in the secretory crypt cells in the mammalian intestine is the one that absorbs the amino acid glutamine. Majority of the amino acid transporters are sodium dependent and therefore require basolateral membrane Na-K-ATPase to maintain an efficient transcellular Na gradient for their activity. These transport processes are tightly regulated by various cellular and molecular mechanisms that facilitate their optimal activity during normal physiological processes. Malabsorption of amino acids, recently described in pathophysiological states such as in inflammatory bowel disease (IBD), is undoubtedly responsible for the debilitating symptoms of IBD such as malnutrition, weight loss and ultimately a failure to thrive. Also recently, in vivo models of IBD and in vitro studies have demonstrated that specific immune-inflammatory mediators/pathways regulate specific amino acid transporters. This provides possibilities to derive novel nutrition and immune-based treatment options for conditions such as IBD. © 2020 American Physiological Society. Compr Physiol 10:673-686, 2020.
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Affiliation(s)
- Soudamani Singh
- Department of Clinical and Translational Sciences and Appalachian Clinical and Translational Science Institute, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia, USA
| | - Subha Arthur
- Department of Clinical and Translational Sciences and Appalachian Clinical and Translational Science Institute, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia, USA
| | - Uma Sundaram
- Department of Clinical and Translational Sciences and Appalachian Clinical and Translational Science Institute, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia, USA
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Park JY, Lee JW, Lee CH, Lee HJ, Kang KS. Synthesis and inhibitory effect of cis-guggulsterone on lipopolysaccharide-induced production of nitric oxide in macrophages. Bioorg Med Chem Lett 2020; 30:126962. [PMID: 31980338 DOI: 10.1016/j.bmcl.2020.126962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 12/29/2019] [Accepted: 01/04/2020] [Indexed: 10/25/2022]
Abstract
Guggulsterone is a bioactive plant sterol naturally found in migratory plants. It exists in various forms, and its active compounds include the isomers cis-guggulsterone (E-GS) and trans-guggulsterone (Z-GS). In this study, the anti-inflammatory effects of these two isomeric pregnadienedione steroids were investigated against lipopolysaccharide-induced inflammatory reaction in RAW264.7 mouse macrophages. Our results showed that both guggulsterones inhibited the production of NO in macrophages treated with lipopolysaccharide, with IC50 values ranging from 3.0 to 6.7 μM. E-GS exerted higher efficacy than Z-GS, and its anti-inflammatory effects was mediated through inhibition of iNOS and COX-2 expression.
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Affiliation(s)
- Jun Yeon Park
- Department of Food Science and Biotechnology, Kyonggi University, Suwon 16227, Republic of Korea
| | - Jae Wook Lee
- Natural Product Research Center, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea; Convergent Research Center for Dementia, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea; Department of Biological Chemistry, Korea University of Science and Technology, Daejeon 34113, Republic of Korea
| | - Chang-Ho Lee
- Research Group of Functional Food Materials, Korea Food Research Institute, Wanju 55365, Republic of Korea
| | - Hae-Jeung Lee
- Department of Food and Nutrition, Gachon University, Gyeonggi-do 13120, Republic of Korea.
| | - Ki Sung Kang
- College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea.
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Abstract
Increased endothelial cell adhesion molecule (ECAM) expression, leukocyte-endothelial cell adhesive interactions (LECA), platelet-endothelial cell adhesion (PECA), mast cell activation, production of reactive oxygen species (ROS), and microvascular permeability are hallmarks of the inflammatory response. The infiltration of inflammatory phagocytes is associated with myeloperoxidase (MPO)-dependent production of hypochlorous acid, a reactive chlorinating species that targets membrane lipids to produce halogenated lipids such as 2-chlorohexadecanal (2-ClHDA) and 2-chloropalmitic acid (2-ClPA). Whether these chlorinated lipids contribute to microcirculatory dysfunction is largely unknown. Thus, the objectives of this study were to determine if chlorinated lipids exposure induces such inflammatory responses in an in vitro model employing cultured human intestinal mesenteric vascular endothelial cells (HIMVEC), and in an in vivo model examining responses in small intestinal and mesenteric postcapillary venules of naive rats. Following the addition of either 2-ClPA or 2-ClHDA to the culture medium, HIMVEC displayed increased platelet and neutrophil adherence that was associated with elevated expression of ECAMs and increased permeability. In vivo, chlorinated lipid exposure significantly increased LECA, PECA, ROS production, and albumin leakage, inflammatory events that were associated with mast cell activation and increased tissue MPO activity and expression. Our data provide proof-of-principle that 2-ClPA and 2-ClHDA induce powerful proinflammatory responses both in vitro and in vivo, suggesting the possibility that these chlorinated lipid products of the MPO/ hydrogen peroxide /chloride system may contribute to inflammation noted in neutrophil-dependent, myeloperoxidase-mediated pathologic states such as ischemia/reperfusion, hemorrhagic shock, and sepsis.
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Kaneguchi A, Ozawa J, Minamimoto K, Yamaoka K. Nitric oxide synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME) attenuates remobilization-induced joint inflammation. Nitric Oxide 2020; 96:13-19. [PMID: 31926320 DOI: 10.1016/j.niox.2020.01.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Revised: 12/19/2019] [Accepted: 01/06/2020] [Indexed: 12/14/2022]
Abstract
Shortly after joint remobilization, inflammation is induced in the joint and aggravates joint contracture via subsequent fibrosis. However, the mechanisms involved in remobilization-induced inflammation are not yet fully understood. We hypothesized that joint immobilization followed by remobilization induces hypoxia/reoxygenation, initiating inflammatory reactions through nitric oxide (NO) production via NO synthase 2 (NOS2). This study aimed to investigate whether: 1) administration of the NOS inhibitor L-NG-nitroarginine methyl ester (l-NAME) can attenuate remobilization-induced joint inflammation; and 2) hypoxia/reoxygenation is induced by joint immobilization and followed by remobilization. Unilateral knee joints of rats were immobilized using external fixators for three weeks. After removal of the fixation device, knees were allowed to move freely for one day (remobilization) with or without l-NAME administration. Without l-NAME administration, inflammatory reactions including joint swelling and inflammatory cell infiltration, edema, and upregulation of inflammatory mediator genes in the joint capsule were detected following upregulation of the NOS2 gene after remobilization. These remobilization-induced inflammatory reactions were partially attenuated by administration of l-NAME. Therefore, NOS2/NO elevation has potential as a novel treatment for remobilization-induced joint inflammation. Gene expression of the hypoxia marker hypoxia inducible factor-1α was upregulated after one day of remobilization, rather than after immobilization. These results suggest that upregulation of NOS2 by remobilization might be not due to hypoxia/reoxygenation.
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Affiliation(s)
- Akinori Kaneguchi
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan
| | - Junya Ozawa
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan.
| | - Kengo Minamimoto
- Major in Medical Engineering and Technology, Graduate School of Medical Technology and Health Welfare Sciences, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan
| | - Kaoru Yamaoka
- Department of Rehabilitation, Faculty of Rehabilitation, Hiroshima International University, Kurose-Gakuendai 555-36, Higashi-Hiroshima, Hiroshima, Japan
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Tristetraprolin targets Nos2 expression in the colonic epithelium. Sci Rep 2019; 9:14413. [PMID: 31595002 PMCID: PMC6783411 DOI: 10.1038/s41598-019-50957-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Accepted: 09/18/2019] [Indexed: 12/15/2022] Open
Abstract
Tristetraprolin (TTP), encoded by the Zfp36 gene, is a zinc-finger protein that regulates RNA stability primarily through association with 3′ untranslated regions (3′ UTRs) of target mRNAs. While TTP is expressed abundantly in the intestines, its function in intestinal epithelial cells (IECs) is unknown. Here we used a cre-lox system to remove Zfp36 in the mouse epithelium to uncover a role for TTP in IECs and to identify target genes in these cells. While TTP was largely dispensable for establishment and maintenance of the colonic epithelium, we found an expansion of the proliferative zone and an increase in goblet cell numbers in the colon crypts of Zfp36ΔIEC mice. Furthermore, through RNA-sequencing of transcripts isolated from the colons of Zfp36fl/fl and Zfp36ΔIEC mice, we found that expression of inducible nitric oxide synthase (iNos or Nos2) was elevated in TTP-knockout IECs. We demonstrate that TTP interacts with AU-rich elements in the Nos2 3′ UTR and suppresses Nos2 expression. In comparison to control Zfp36fl/fl mice, Zfp36ΔIEC mice were less susceptible to dextran sodium sulfate (DSS)-induced acute colitis. Together, these results demonstrate that TTP in IECs targets Nos2 expression and aggravates acute colitis.
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Liu H, Walden TB, Ahl D, Nyman M, Bertilsson S, Phillipson M, Holm L. High‐Fat Diet Enriched with Bilberry Modifies Colonic Mucus Dynamics and Restores Marked Alterations of Gut Microbiome in Rats. Mol Nutr Food Res 2019; 63:e1900117. [DOI: 10.1002/mnfr.201900117] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 07/10/2019] [Indexed: 12/29/2022]
Affiliation(s)
- Hao‐Yu Liu
- Department of Medical Cell BiologyUppsala University Uppsala 75123 Sweden
| | - Tomas B. Walden
- Department of Medical Cell BiologyUppsala University Uppsala 75123 Sweden
| | - David Ahl
- Department of Medical Cell BiologyUppsala University Uppsala 75123 Sweden
| | - Margareta Nyman
- Department of Food Technology, Engineering and NutritionLund University Lund 22100 Sweden
| | - Stefan Bertilsson
- Department of Ecology and Genetics, Limnology and Science for Life LaboratoryUppsala University Uppsala 75236 Sweden
| | - Mia Phillipson
- Department of Medical Cell BiologyUppsala University Uppsala 75123 Sweden
| | - Lena Holm
- Department of Medical Cell BiologyUppsala University Uppsala 75123 Sweden
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Maryam S, Khan MR, Shah SA, Zahra Z, Batool R, Zai JA. Evaluation of anti-inflammatory potential of the leaves of Wendlandia heynei (Schult.) Santapau & Merchant in Sprague Dawley rat. JOURNAL OF ETHNOPHARMACOLOGY 2019; 238:111849. [PMID: 30953822 DOI: 10.1016/j.jep.2019.111849] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Revised: 03/29/2019] [Accepted: 03/31/2019] [Indexed: 06/09/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The leaves of W. heynei (family: Rubiaceae) are used by the folklore in swelling, wounds and body aches. In this study anti-inflammatory potential of W. heynei leaves has been evaluated during in vitro studies and in rat. METHODS Methanol extract of the leaves of W. heynei (WHLM) and its fractions; n-hexane (WHLH), chloroform (WHLC), ethyl acetate (WHLE), n-butanol (WHLB) and residual soluble aqueous (WHLA) were screened for phytochemical analysis and several active constituents (alkaloids, flavonoids, saponins, tannins, terpenoids, β-carotene and lycopene) were also quantified. Heat induced albumin denaturation assay and in vitro cell cultures was carried out for in vitro anti-inflammatory activity, while various in vivo assays like TPA induced ear edema, croton oil induced anus edema, formalin and carrageenan-induced hind paw edema was investigated in Sprague-Dawley rats. Alterations on levels of tumor necrosis factor (TNF-α), Interleukin-1β (IL-1β), IL-6 and prostaglandins (PGE2) induced with WHLE was studied in serum after carrageenan induced paw edema in rat. Meanwhile, the dose dependent WHLE inhibition of NFκB pathway via regulation of the phosphorylation of IKKs, IκBα, and p65 subunit was studied in LPS-induced rat peritoneal macrophages. On account of marked anti-inflammatory activity of WHLE its bioactive components were analyzed by HPLC-DAD analysis. RESULTS The phytochemical analysis yielded alkaloids, saponins, tannins, coumarins, glycosides, quinones and vitamin C in WHLM and in all fractions. Fraction (WHLE) was enriched with alkaloids (20.20 ± 2.5%), flavonoids (25.26 ± 2.11%) and tannins (307.2 ± 2.03 mg of GAE/g of extract), while terpenoids (21.60 ± 1.65%) were the major constituents of WHLH. Ethyl acetate fraction convincingly protected heat induced albumin denaturation. WHLE exhibited highest edema inhibition in models of TPA-induced ear edema (74.51 ± 2.05) and croton oil-induced anal edema (75.38 ± 2.83). The pretreatment with WHLE significantly (p < 0.05) reduced the paw edema with formalin (78.99 ± 2.26%) assessed after 6 h and in carrageenan (75.71 ± 4.46%) was detected after 4 h. Level of anti-inflammatory markers; IL-1β, IL-6, TNF-α and PGE2 in carrageenan induced paw edema in serum of rat was significantly (p < 0.001) decreased with WHLE pretreatment to rat. WHLE significantly inhibited the NFκB by reducing the phosphorylation of IKKs, IκBα, and p65 subunit in LPS-induced inflammation in rat peritoneal macrophages. HPLC-DAD analysis of WHLE indicated the presence of rutin, gallic acid, catechin, caffeic acid and myricetin. CONCLUSIONS It is concluded that WHLM fractions have marked anti-inflammatory activity and this study endorsed the folklore use of W. heynei leaves for swelling related disorders.
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Affiliation(s)
- Sonia Maryam
- Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
| | - Muhammad Rashid Khan
- Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
| | - Sayed Afzal Shah
- Department of Plant Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
| | - Zartash Zahra
- Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
| | - Riffat Batool
- Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
| | - Jawaid Ahmed Zai
- Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
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Palaniappan B, Manoharan P, Arthur S, Singh S, Murughiyan U, Sundaram U. Stimulation of constitutive nitric oxide uniquely and compensatorily regulates intestinal epithelial cell brush border membrane Na absorption. Physiol Rep 2019; 7:e14086. [PMID: 31074207 PMCID: PMC6509550 DOI: 10.14814/phy2.14086] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Revised: 04/10/2019] [Accepted: 04/12/2019] [Indexed: 02/04/2023] Open
Abstract
In the mammalian small intestine, sodium is primarily absorbed by Na+ /H+ exchange (NHE3) and Na-glucose cotransport (SGLT1) in the brush border membrane (BBM) of villus cells. However, how enhanced cellular constitutive nitric oxide (cNO) may affect NHE3 and SGLT1 remains unclear. Both in vivo in rabbit intestinal villus cells and in vitro IEC-18 cells, administration of NO donor, GSNAP, modestly increased cNO. GSNAP stimulated SGLT1 in villus and IEC-18 cells. The mechanism of stimulation was secondary to an increase in the affinity of SGLT1 for glucose. The change in SGLT1 was not secondary to altered Na-extruding capacity of the cell since Na+ /K+ -ATPase was decreased by GSNAP treatment. In contrast, GSNAP inhibited NHE3 activity in villus cell BBM. The mechanism of NHE3 inhibition was secondary to reduced BBM transporter numbers. These studies demonstrated that the physiological increase in cNO uniquely regulates mammalian small intestinal NHE3 and SGLT1 to maintain Na homeostasis.
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Affiliation(s)
- Balasubramanian Palaniappan
- Department of Clinical and Translational SciencesJoan C Edwards School of MedicineMarshall UniversityHuntingtonWest Virginia
| | - Palanikumar Manoharan
- Department of Clinical and Translational SciencesJoan C Edwards School of MedicineMarshall UniversityHuntingtonWest Virginia
| | - Subha Arthur
- Department of Clinical and Translational SciencesJoan C Edwards School of MedicineMarshall UniversityHuntingtonWest Virginia
| | - Soudamani Singh
- Department of Clinical and Translational SciencesJoan C Edwards School of MedicineMarshall UniversityHuntingtonWest Virginia
| | - Usha Murughiyan
- Department of Clinical and Translational SciencesJoan C Edwards School of MedicineMarshall UniversityHuntingtonWest Virginia
| | - Uma Sundaram
- Department of Clinical and Translational SciencesJoan C Edwards School of MedicineMarshall UniversityHuntingtonWest Virginia
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Zengin G, Stefanucci A, Rodrigues MJ, Mollica A, Custodio L, Aumeeruddy MZ, Mahomoodally MF. Scrophularia lucida L. as a valuable source of bioactive compounds for pharmaceutical applications: In vitro antioxidant, anti-inflammatory, enzyme inhibitory properties, in silico studies, and HPLC profiles. J Pharm Biomed Anal 2019; 162:225-233. [PMID: 30268023 DOI: 10.1016/j.jpba.2018.09.035] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2018] [Revised: 09/16/2018] [Accepted: 09/17/2018] [Indexed: 01/10/2023]
Abstract
The genus Scrophularia has received much interest with regards to its traditional uses against eczema, psoriasis, and mastitis. Yet, the medicinal properties of some species still need to be scientifically validated. The present study was designed to investigate into the biological properties of various solvent extracts (ethyl acetate, methanol, and aqueous) of the roots and aerial parts of Scrophularia lucida based on its antioxidant, anti-inflammatory, and enzyme inhibitory activities together with phytochemical screening. Our results revealed that the solvent extracts differed in their biological effectiveness. The root ethyl acetate extract showed the highest ABTS scavenging, FRAP, CUPRAC, and inhibitory activity against AChE and α-glucosidase. The ethyl acetate extract of the aerial parts displayed the highest BChE and α-amylase inhibition and antioxidant effect in the phosphomolybdenum assay, while the methanol extracts of both parts were the most effective DPPH• scavengers and tyrosinase inhibitors. The methanol extracts of the root and aerial parts also inhibited NO production in lipopolysaccharide (LPS)-stimulated murine leukemic monocyte-macrophage cell (4.99% and 10.77%, respectively), at 31.25 μg/mL concentration. The highest TPC (34.98 mg GAE/g extract) and TFC (48.33 mg RE/g extract) were observed in the ethyl acetate extract of the root and aerial parts, respectively. The most abundant compounds in the root ethyl acetate extract were luteolin (852 μg/g extract), rosmarinic acid (522 μg/g extract), and hesperidin (394 μg/g extract) while kaempferol was most abundant in the ethyl acetate extract of the aerial parts (628 μg/g extract). In silico experiments were conducted on tyrosinase and the higher docking values were observed for rosmarinic acid and hesperidin. The present findings provide base line information which tend to support the potential use of S. lucida in the management of several chronic diseases, including Alzheimer's disease and diabetes mellitus.
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Affiliation(s)
- Gokhan Zengin
- Selcuk University, Science Faculty, Department of Biology, Campıus, Konya, Turkey.
| | - Azzurra Stefanucci
- Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, 66100, Chieti, Italy
| | - Maria João Rodrigues
- Centre of Marine Sciences, University of Algarve, Faculty of Sciences and Technology, Ed. 7, Campus of Gambelas, 8005-139, Faro, Portugal
| | - Adriano Mollica
- Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, 66100, Chieti, Italy
| | - Luisa Custodio
- Department of Health Sciences, Faculty of Science, University of Mauritius, 230, Réduit, Mauritius
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Combination of phenolic profiles, pharmacological properties and in silico studies to provide new insights on Silene salsuginea from Turkey. Comput Biol Chem 2018; 77:178-186. [DOI: 10.1016/j.compbiolchem.2018.10.005] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Revised: 10/05/2018] [Accepted: 10/05/2018] [Indexed: 01/17/2023]
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Sun Y, Shi X, Zheng X, Nie S, Xu X. Inhibition of dextran sodium sulfate-induced colitis in mice by baker's yeast polysaccharides. Carbohydr Polym 2018; 207:371-381. [PMID: 30600019 DOI: 10.1016/j.carbpol.2018.11.087] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 11/07/2018] [Accepted: 11/27/2018] [Indexed: 12/19/2022]
Abstract
Most of the reported yeast polysaccharides are a mixture of chitin, β-glucan and mannoprotein, leading to different biological activities. Herein, we report the structures and the anti-inflammation of the purified baker's yeast polysaccharides (BBG1-BBG4). Experimental data indicated that BBG1 was a highly branched β-(1,6)-glucan linked to mannoprotein; BBG2 was a linear β-(1,3)-glucan; BBG3 and BBG4 were mixtures of a β-(1,6)-branched β-(1,3)-glucan and a linear β-(1,3)-glucan. Of these, BBG1 exhibited stronger inhibition of pro-inflammatory mediators of NO/iNOS, IL-6, IL-1β, etc. at protein and/or mRNA levels in LPS-stimulated RAW264.7 cells through inhibiting MAPK signalling pathways. Orally administered BBG1 and BBG2 significantly decreased the pro-inflammatory mediators of IL-6, iNOS and IL-1β at protein and/or mRNA levels, as well as colonic mucosal damage and macrophages infiltration in DSS-induced colitis mice. All these findings suggest that yeast polysaccharides have potentials as anti-inflammatory drugs or adjuvants in the intestinal inflammation therapy.
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Affiliation(s)
- Ying Sun
- College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China
| | - Xiaodan Shi
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, China
| | - Xing Zheng
- College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China
| | - Shaoping Nie
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, 330047, China.
| | - Xiaojuan Xu
- College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China.
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CUI XY, SUN NN, XIE XN, SUN WC, ZHAO Q, LIU N. Detection of Newly Synthesized Proteins via Metabolic Incorporation of Non-natural Amino Acid. CHINESE JOURNAL OF ANALYTICAL CHEMISTRY 2018. [DOI: 10.1016/s1872-2040(18)61125-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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45
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Liao W, He X, Yi Z, Xiang W, Ding Y. Chelidonine suppresses LPS-Induced production of inflammatory mediators through the inhibitory of the TLR4/NF-κB signaling pathway in RAW264.7 macrophages. Biomed Pharmacother 2018; 107:1151-1159. [PMID: 30257328 DOI: 10.1016/j.biopha.2018.08.094] [Citation(s) in RCA: 45] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2018] [Revised: 08/07/2018] [Accepted: 08/17/2018] [Indexed: 12/19/2022] Open
Abstract
Chelidonine is one of the alkaloids of Chelidonium majus, which has broad pharmacological activities, including anti-inflammatory. Despite chelidonine has been shown to exhibit anti-inflammatory activity, the molecular mechanisms are not yet fully elucidated. In this paper, we used RAW264.7 macrophages and mice to investigate the anti-inflammatory effects of chelidonine. Firstly, we found that chelidonine significantly suppressed LPS-induced the production of NO and PGE2, as well as iNOS and COX-2 mRNA and protein expression. In addition, pro-inflammatory cytokines induced by LPS, such as TNFα and IL-6 were also attenuated by chelidonine. What's more, LPS-induced activation and degradation of IκBα followed by translocation of the p65 from the cytoplasm to the nucleus were attenuated by chelidonine. Furthermore, chelidonine even significantly inhibited TLR4 expression induced by LPS. Finally, we verified that chelidonine striking ly decreased serum TNFα, IL-6 and PGE2 levels in LPS stimulated mice. Taken together, this study demonstrated that chelidonine may suppressed the LPS-induced inflammatory response both in vitro and in vivo, which was relating to TLR4/NF-κB signaling pathway disturbed by chelidonine.
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Affiliation(s)
- Wang Liao
- Department of Cardiology, Hainan General Hospital, Haikou 570102, China
| | - Xiaojie He
- Department of Nephropathy, Children's Medical Center, The Second Xiangya Hospital, Cal South University, Changsha 410000, China
| | - Zhuwen Yi
- Department of Nephropathy, Children's Medical Center, The Second Xiangya Hospital, Cal South University, Changsha 410000, China
| | - Wei Xiang
- Department of Pediatrics, Maternal and Child Health Care Hospital of Hainan Province, 15 LongKun-Nan Road, Haikou 570206, China.
| | - Yan Ding
- Department of Dermatology, Hainan Provincial Hospital of Skin Disease, 49 LongKun-Nan Road, Haikou 570206, China.
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46
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Jayesh K, Karishma R, Vysakh A, Gopika P, Latha MS. Terminalia bellirica (Gaertn.) Roxb fruit exerts anti-inflammatory effect via regulating arachidonic acid pathway and pro-inflammatory cytokines in lipopolysaccharide-induced RAW 264.7 macrophages. Inflammopharmacology 2018; 28:10.1007/s10787-018-0513-x. [PMID: 30003465 DOI: 10.1007/s10787-018-0513-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Accepted: 07/03/2018] [Indexed: 12/31/2022]
Abstract
Terminalia bellirica (Gaertn.) Roxb. (Family: Combretaceae), known as Bhibhitaki in Sanskrit and locally known as Behera in India, has been used for centuries in Ayurveda, a universal system of medicine in India. The dried fruit of T. bellirica is used for the treatment of several disorders. The present study aims to explore the anti-inflammatory effects of aqueous acetone extracts isolated from T. bellirica (AATB) in RAW 264.7 cell lines. The AATB was prepared from the fruits of T. bellirica. Different concentrations of AATB (6.25-100 μg/ml) were used for MTT assay. The anti-inflammatory effect of AATB was evaluated by using different assays such as total cyclooxygenase (COX), 5-lipoxygenase (5-LOX) activity, nitrate and reactive oxygen species (ROS) production. The mRNA level expression of COX-2, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were studied in LPS stimulated RAW 264.7 cells. AATB treatment significantly diminished the elevated levels of inflammatory markers. Moreover, AATB downregulated the mRNA level expression of TNF-α, IL-6 and COX-2 genes. The result of our study suggest the use of AATB and is able to reduce inflammatory conditions associated with various diseases.
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Affiliation(s)
- Kuriakose Jayesh
- School of Biosciences, Mahatma Gandhi University, Priyadarshini Hills, Kottayam, Kerala, India
| | - Raj Karishma
- School of Biosciences, Mahatma Gandhi University, Priyadarshini Hills, Kottayam, Kerala, India
| | - A Vysakh
- School of Biosciences, Mahatma Gandhi University, Priyadarshini Hills, Kottayam, Kerala, India
| | - Prasad Gopika
- School of Biosciences, Mahatma Gandhi University, Priyadarshini Hills, Kottayam, Kerala, India
| | - M S Latha
- School of Biosciences, Mahatma Gandhi University, Priyadarshini Hills, Kottayam, Kerala, India.
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Nadatani Y, Watanabe T, Shimada S, Otani K, Tanigawa T, Fujiwara Y. Microbiome and intestinal ischemia/reperfusion injury. J Clin Biochem Nutr 2018; 63:26-32. [PMID: 30087540 PMCID: PMC6064812 DOI: 10.3164/jcbn.17-137] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Accepted: 03/22/2018] [Indexed: 12/12/2022] Open
Abstract
Intestinal ischemia/reperfusion injury is a severe disease associated with a high mortality. The mechanisms that cause ischemia/reperfusion injury are complex and many factors are involved in the injury formation process; however, the only available treatment is surgical intervention. Recent studies demonstrated that the intestinal microbiome plays a key role in intestinal ischemia/reperfusion injury and there are many factors associated with intestinal bacteria during the formation of the intestinal ischemia/reperfusion injury. Among the Toll-like receptors (TLR), TLR2, TLR4, and their adaptor protein, myeloid differentiation primary-response 88 (MyD88), have been reported to be involved in intestinal ischemia/reperfusion injury. Oxidative stress and nitric oxide are also associated with intestinal bacteria during the formation of the intestinal ischemia/reperfusion injury. This review focuses on our current understanding of the impact of the microbiome, including the roles of the TLRs, oxidative stress, and nitric oxide, on intestinal ischemia/reperfusion injury.
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Affiliation(s)
- Yuji Nadatani
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka City, Osaka 545-8585, Japan
| | - Toshio Watanabe
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka City, Osaka 545-8585, Japan
| | - Sunao Shimada
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka City, Osaka 545-8585, Japan
| | - Koji Otani
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka City, Osaka 545-8585, Japan
| | - Tetsuya Tanigawa
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka City, Osaka 545-8585, Japan
| | - Yasuhiro Fujiwara
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka City, Osaka 545-8585, Japan
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48
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Olive oil polyphenols reduce oxysterols -induced redox imbalance and pro-inflammatory response in intestinal cells. Redox Biol 2018; 17:348-354. [PMID: 29793168 PMCID: PMC6007813 DOI: 10.1016/j.redox.2018.05.006] [Citation(s) in RCA: 81] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 04/30/2018] [Accepted: 05/12/2018] [Indexed: 02/07/2023] Open
Abstract
Dietary habits may strongly influence intestinal homeostasis. Oxysterols, the oxidized products of cholesterol present in cholesterol-containing foodstuffs, have been shown to exert pro-oxidant and pro-inflammatory effects, altering intestinal epithelial layer and thus contributing to the pathogenesis of human inflammatory bowel diseases and colon cancer. Extra virgin olive oil polyphenols possess antioxidant and anti-inflammatory properties, and concentrate in the intestinal lumen, where may help in preventing intestinal diseases. In the present study we evaluated the ability of an extra virgin olive oil phenolic extract to counteract the pro-oxidant and pro-inflammatory action of a representative mixture of dietary oxysterols in the human colon adenocarcinoma cell line (Caco-2) undergoing full differentiation into enterocyte-like cells. Oxysterols treatment significantly altered differentiated Caco-2 cells redox status, leading to oxidant species production and a decrease of GSH levels, after 1 h exposure, followed by an increase of cytokines production, IL-6 and IL-8, after 24 h. Oxysterol cell treatment also induced after 48 h an increase of NO release, due to the induction of iNOS. Pretreatment with the phenolic extract counteracted oxysterols effects, at least in part by modulating one of the main pathways activated in the cellular response to the action of oxysterols, the MAPK-NF-kB pathway. We demonstrated the ability of the phenolic extract to directly modulate p38 and JNK1/2 phosphorylation and activation of NF-kB, following its inhibitor IkB phosphorylation. The phenolic extract also inhibited iNOS induction, keeping NO concentration at the control level. Our results suggest a protective effect at intestinal level of extra virgin olive oil polyphenols, able to prevent or limit redox unbalance and the onset and progression of chronic intestinal inflammation.
Dietary oxysterols exerted pro-oxidant and pro-inflammatory effects in differentiated Caco-2 cells. H2O2 production, GSH decrease, IL-6 and IL-8 release were detected. NO release due to iNOS induction was higher than controls in oxysterols treated cells. Olive oil phenolic extract efficiently counteracted oxysterols effects. Phenolic extract directly modulated p38 and JNK MAPK/NF-κB signaling axis.
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49
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Najafi M, Motevaseli E, Shirazi A, Geraily G, Rezaeyan A, Norouzi F, Rezapoor S, Abdollahi H. Mechanisms of inflammatory responses to radiation and normal tissues toxicity: clinical implications. Int J Radiat Biol 2018; 94:335-356. [PMID: 29504497 DOI: 10.1080/09553002.2018.1440092] [Citation(s) in RCA: 123] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Revised: 01/23/2018] [Accepted: 01/31/2018] [Indexed: 02/06/2023]
Abstract
PURPOSE Cancer treatment is one of the most challenging diseases in the present era. Among a few modalities for cancer therapy, radiotherapy plays a pivotal role in more than half of all treatments alone or combined with other cancer treatment modalities. Management of normal tissue toxicity induced by radiation is one of the most important limiting factors for an appropriate radiation treatment course. The evaluation of mechanisms of normal tissue toxicity has shown that immune responses especially inflammatory responses play a key role in both early and late side effects of exposure to ionizing radiation (IR). DNA damage and cell death, as well as damage to some organelles such as mitochondria initiate several signaling pathways that result in the response of immune cells. Massive cell damage which is a common phenomenon following exposure to a high dose of IR cause secretion of a lot of inflammatory mediators including cytokines and chemokines. These mediators initiate different changes in normal tissues that may continue for a long time after irradiation. In this study, we reviewed the mechanisms of inflammatory responses to IR that are involved in normal tissue toxicity and considered as the most important limiting factors in radiotherapy. Also, we introduced some agents that have been proposed for management of these responses. CONCLUSIONS The early inflammation during the radiation treatment is often a limiting factor in radiotherapy. In addition to the limiting factors, chronic inflammatory responses may increase the risk of second primary cancers through continuous free radical production, attenuation of tumor suppressor genes, and activation of oncogenes. Moreover, these effects may influence non-irradiated tissues through a mechanism named bystander effect.
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Affiliation(s)
- Masoud Najafi
- a Radiology and Nuclear Medicine Department, School of Paramedical Sciences , Kermanshah University of Medical Science , Kermanshah , Iran
| | - Elahe Motevaseli
- b Department of Molecular Medicine, School of Advanced Technologies in Medicine , Tehran University of Medical Sciences , Tehran , Iran
| | - Alireza Shirazi
- c Department of Medical Physics and Biomedical Engineering, Faculty of Medicine , Tehran University of Medical Sciences , Tehran , Iran
| | - Ghazale Geraily
- c Department of Medical Physics and Biomedical Engineering, Faculty of Medicine , Tehran University of Medical Sciences , Tehran , Iran
| | - Abolhasan Rezaeyan
- d Department of Medical Physics, School of Medicine , Iran University of Medical Sciences , Tehran , Iran
| | - Farzad Norouzi
- e Science and Research Branch , Azad University , Tehran , Iran
| | - Saeed Rezapoor
- f Department of Radiology, Faculty of Paramedical Sciences , Tehran University of Medical Sciences , Tehran , Iran
| | - Hamid Abdollahi
- d Department of Medical Physics, School of Medicine , Iran University of Medical Sciences , Tehran , Iran
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50
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Kim GA, Ginga NJ, Takayama S. Integration of Sensors in Gastrointestinal Organoid Culture for Biological Analysis. Cell Mol Gastroenterol Hepatol 2018; 6:123-131.e1. [PMID: 29928682 PMCID: PMC6007820 DOI: 10.1016/j.jcmgh.2018.03.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2017] [Accepted: 03/19/2018] [Indexed: 12/11/2022]
Abstract
The gastrointestinal (GI) tract regulates physiologic responses in complex ways beyond facilitating nutrient entry into the circulatory system. Because of the anatomic location of the GI tract, studying in vivo physiology of the human gut, including host cell interaction with the microbiota, is limited. GI organoids derived from human stem cells are gaining interest as they recapitulate in vivo cellular phenotypes and functions. An underdeveloped capability that would further enhance the utility of these miniature models of the GI tract is to use sensors to quantitatively characterize the organoid systems with high spatiotemporal resolution. In this review, we first discuss tools to capture changes in the fluid milieu of organoid cultures both in the organoid exterior as well as the luminal side of the organoids. The subsequent section describes approaches to characterize barrier functions across the epithelial layer of the GI organoids directly or after transferring the epithelial cells to a 2-dimensional culture format in Transwells or compartmentalized microchannel devices. The final section introduces recently developed bioengineered bacterial sensors that sense intestinal inflammation-related small molecules in the lumen using lambda cI/Cro genetic elements or fluorescence as readouts. Considering the small size and cystic shape of GI organoids, sensors used in conventional macroscopic intestinal models are often not suitable, particularly for time-lapse monitoring. Unmet needs for GI organoid analysis provides many opportunities for the development of noninvasive and miniaturized biosensors.
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Key Words
- 2D, 2-dimensional
- 3D, 3-dimensional
- Bioengineered Sensor
- FITC, fluorescein isothiocyanate
- FITC-Dex, fluorescein isothiocyanate-dextran
- GI Organoids
- GI, gastrointestinal
- HIO, human intestinal organoid
- NO, nitric oxide
- Organoid Microenvironment
- RT-PCR, reverse-transcription polymerase chain reaction
- SNARF, seminaphtharhodafluor
- TCRS, 2-component regulatory system
- TEER, transepithelial/transendothelial electric resistance
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Affiliation(s)
- Ge-Ah Kim
- Department of Materials Science and Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, Georgia
| | - Nicholas J. Ginga
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, Georgia
| | - Shuichi Takayama
- The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, Georgia
- Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan
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