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Bakrim S, Fessikh ME, Elhrech H, Omari NE, Amanullah M, Ming LC, Moshawih S, Bouyahya A. Targeting inflammation in cancer therapy: from mechanistic insights to emerging therapeutic approaches. J Transl Med 2025; 23:588. [PMID: 40420174 DOI: 10.1186/s12967-025-06583-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2025] [Accepted: 05/07/2025] [Indexed: 05/28/2025] Open
Abstract
Inflammation is a complex and finely tuned component of the host defense mechanism, responding sensitively to a range of physical, chemical, and biological stressors. Current research is advancing our grasp of both cellular and molecular mechanisms that initiate and regulate interactions within inflammatory pathways. Substantial evidence now indicates a profound link between inflammation, innate immunity, and cancer. Dysregulation of inflammatory pathways is known to be a pivotal factor in the induction, growth, and metastasis of tumors through multiple mechanistic pathways. Basically, the tumor microenvironment (TME), characterized by dynamic interplay between cancerous cells and surrounding inflammatory and stromal cells, plays a central role in these processes. Increasingly, controlled acute inflammation is being explored as a promising therapeutic tool in certain types of cancer. However, inflammatory cells in the TME exhibit remarkable plasticity, with shifting phenotypic and functional roles that facilitate cancer cell survival, proliferation, and migration, especially under chronic inflammatory conditions. Additionally, signaling molecules associated with the innate immune system, like chemokines, are co-opted by malignant cells to support invasion, migration, and metastasis. These findings underscore the need for deeper insights into the mechanisms connecting inflammation to cancer pathology, which could pave the way for innovative diagnostic approaches and targeted anti-inflammatory therapies to counter tumor development. The current review underlines the critical involvement of inflammation in cancer development, examining the connection between the immune system, key inflammatory mediators, biomarkers, and their associated pathways in cancer. We also discuss the impact of inflammation-targeted therapies on anticancer signaling pathways. Furthermore, we review major anti-inflammatory drugs with potential applications in oncology, assessing how inflammation is modulated in cancer management. Lastly, we outline an overview of ongoing discoveries in the field, highlighting both the challenges and the therapeutic promise of targeting inflammation in cancer therapy.
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Affiliation(s)
- Saad Bakrim
- Geo-Bio-Environment Engineering and Innovation Laboratory, Molecular Engineering, Biotechnology and Innovation Team, Polydisciplinary Faculty of Taroudant, Ibn Zohr University, Agadir, 80000, Morocco
| | - Meriem El Fessikh
- Laboratory of Human Pathologies Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat, Morocco
| | - Hamza Elhrech
- Laboratory of Human Pathologies Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat, Morocco
| | - Nasreddine El Omari
- High Institute of Nursing Professions and Health Techniques of Tetouan, Tetouan, Morocco
| | - Mohammed Amanullah
- Department of clinical Biochemistry, College of Medicine, King Khalid University, Abha, Kingdom of Saudi Arabia
| | - Long Chiau Ming
- Datta Meghe College of Pharmacy, Datta Meghe Institute of Higher Education and Research (deemed to be University), Sawangi (M), Wardha, India
- Faculty of Medical and Life Sciences, Sunway University, Sunway City, Malaysia
| | - Said Moshawih
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan
| | - Abdelhakim Bouyahya
- Laboratory of Human Pathologies Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat, Morocco.
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman, Jordan.
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Jumaar C, Malefane L, Jacobs S, Sanni O, Louw E, Baines N, Payne C, Schulz S, Lombard C, Feyasa M, Maree D, Windvogel S, Strijdom H, Botha B, Allwood B, Maarman GJ. Delineating the Significance of Several Inflammatory Markers in a Lung Tuberculosis Cohort During the Active and Post-Tuberculosis Stages of the Disease: An Observational Study in Cape Town, South Africa (2019 to 2024). Infect Dis Rep 2025; 17:52. [PMID: 40407654 PMCID: PMC12101205 DOI: 10.3390/idr17030052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 02/18/2025] [Accepted: 04/30/2025] [Indexed: 05/26/2025] Open
Abstract
BACKGROUND Pulmonary tuberculosis (TB) frequently leads to long-term lung complications that contribute to increased mortality. Understanding the pathogenesis of post-TB lung impairments is crucial for improving long-term outcomes in TB patients; yet this area remains poorly researched. METHODS Our study assessed circulatory inflammatory markers in patients who completed TB treatment more than one year before enrolment (population 1) and patients receiving in-hospital treatment for active drug-sensitive TB (population 2). RESULTS IL-6 was seven times higher in both populations compared to the normal range. IL-8 was below the limit of detection (LOD) in population 1, while it was approximately 2.5 times higher in population 2 compared to the normal range. TNF-α was 21 times higher in population 1 and 19 times higher in population 2 compared to the normal range. CRP was almost 49 times higher in both populations, and IL-1Ra was below the LOD in population 1, while it was ~1.5 times higher in population 2 compared to the normal range. CONCLUSIONS These inflammatory biomarkers correlated well with lung function in the post-TB state, and their high levels suggest a persistent pro-inflammatory state post-TB, which may contribute to post-TB lung disease. More research is warranted to better understand this phenomenon, but these findings may highlight a need to consider anti-inflammatory therapy for patients with post-TB lung disease, especially since these high levels of cytokines can directly contribute to lung damage.
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Affiliation(s)
- Chrisstoffel Jumaar
- Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town 8000, South Africa; (C.J.); (L.M.); (S.J.); (O.S.); (S.W.); (H.S.)
| | - Lindiwe Malefane
- Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town 8000, South Africa; (C.J.); (L.M.); (S.J.); (O.S.); (S.W.); (H.S.)
| | - Steve Jacobs
- Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town 8000, South Africa; (C.J.); (L.M.); (S.J.); (O.S.); (S.W.); (H.S.)
| | - Olakunle Sanni
- Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town 8000, South Africa; (C.J.); (L.M.); (S.J.); (O.S.); (S.W.); (H.S.)
| | - Elize Louw
- Division of Pulmonology, Department of Medicine, Faculty of Medicine & Health Sciences, Stellenbosch University & Tygerberg Hospital, Cape Town 8000, South Africa; (E.L.); (N.B.); (S.S.); (D.M.); (B.A.)
| | - Nicola Baines
- Division of Pulmonology, Department of Medicine, Faculty of Medicine & Health Sciences, Stellenbosch University & Tygerberg Hospital, Cape Town 8000, South Africa; (E.L.); (N.B.); (S.S.); (D.M.); (B.A.)
| | - Carmen Payne
- Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town 8000, South Africa; (C.J.); (L.M.); (S.J.); (O.S.); (S.W.); (H.S.)
| | - Sigrid Schulz
- Division of Pulmonology, Department of Medicine, Faculty of Medicine & Health Sciences, Stellenbosch University & Tygerberg Hospital, Cape Town 8000, South Africa; (E.L.); (N.B.); (S.S.); (D.M.); (B.A.)
| | - Carl Lombard
- Biostatistics Research Unit, South African Medical Research Council, Cape Town 8000, South Africa;
| | - Merga Feyasa
- CDT—Africa Center of Excellence, College of Health Sciences, Addis Ababa University, Addis Ababa 10001, Ethiopia;
- Division of Epidemiology and Biostatistics, Department of Global Health, Stellenbosch University, Cape Town 8000, South Africa
| | - David Maree
- Division of Pulmonology, Department of Medicine, Faculty of Medicine & Health Sciences, Stellenbosch University & Tygerberg Hospital, Cape Town 8000, South Africa; (E.L.); (N.B.); (S.S.); (D.M.); (B.A.)
| | - Shantal Windvogel
- Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town 8000, South Africa; (C.J.); (L.M.); (S.J.); (O.S.); (S.W.); (H.S.)
| | - Hans Strijdom
- Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town 8000, South Africa; (C.J.); (L.M.); (S.J.); (O.S.); (S.W.); (H.S.)
| | - Benjamin Botha
- Cape Winelands TB Centre, Brewelskloof Hospital, Worcester 6850, South Africa;
| | - Brian Allwood
- Division of Pulmonology, Department of Medicine, Faculty of Medicine & Health Sciences, Stellenbosch University & Tygerberg Hospital, Cape Town 8000, South Africa; (E.L.); (N.B.); (S.S.); (D.M.); (B.A.)
| | - Gerald J. Maarman
- Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town 8000, South Africa; (C.J.); (L.M.); (S.J.); (O.S.); (S.W.); (H.S.)
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Jiang L, Wu Y, Liu B, Lai K, Ma Y, Chen Z, Qin Z, Xu Z, Lin Z, Chen Z, Tsai CL, Li T. One-Month Silicone Oil Tamponade Can Decrease Intraocular Complications via Reducing the Recruitment and Activation of Leukocytes in Patients with Rhegmatogenous Retinal Detachment. Ophthalmic Res 2025; 68:292-300. [PMID: 40127632 DOI: 10.1159/000545211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 02/22/2025] [Indexed: 03/26/2025]
Abstract
INTRODUCTION The aim of the study was to compare the effects of 1-month versus routine-duration silicone oil (SO) tamponade on intraocular inflammatory cytokine levels and clinical outcomes in patients undergoing vitrectomy for rhegmatogenous retinal detachment. METHODS A prospective study from May 2019 to March 2022 divided patients undergoing vitrectomy into routine and early groups. Aqueous humor was sampled before SO removal to measure cytokine levels, including granulocyte-macrophage colony-stimulating factor, interferon (IFN)-γ, interleukin (IL)-4, IL-8, IL-10, IL-13, IL-17, macrophage inflammatory protein (MIP)-1α, tumor necrosis factor (TNF)-α, and IL-1α. Clinical outcomes such as SO emulsification, cataract formation, recurrent retinal detachment, corneal endothelial cell (CEC) density, and intraocular pressure were assessed. Statistical analyses were performed to evaluate differences and correlations between cytokine levels and clinical characteristics. RESULTS The study analyzed 48 eyes, with 28 in the routine group and 20 in the early group. The early group had significantly lower IL-8 and TNF-α levels (p = 0.006 and p = 0.013) and reduced SO emulsification (p = 0.01). A significant trend toward fewer cataract cases and higher CEC density was observed in the early group (p = 0.019 and p = 0.015). IL-8 and TNF-α levels showed positive correlations with IL-10, MIP-1α. CONCLUSION One-month SO tamponade significantly reduces intraocular inflammatory cytokine levels and associated complications by decreasing the recruitment and activation of leukocytes. These findings suggest that shorter SO placement durations can effectively minimize inflammation-related complications while maintaining therapeutic efficacy. Future research should focus on optimizing SO tamponade protocols and exploring the underlying mechanisms of inflammation and emulsification to enhance the safety and efficacy of vitreoretinal surgeries.
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Affiliation(s)
- Lan Jiang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Yuqing Wu
- Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou, China
| | - Baoyi Liu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
- Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Kunbei Lai
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Yuan Ma
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Ziye Chen
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Zijian Qin
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Zhuojun Xu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Zhuangling Lin
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Zitong Chen
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Chin-Ling Tsai
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
| | - Tao Li
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Clinical Research Center for Ocular Diseases, Guangzhou, China
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Liu X, Zhao P, Wang L, Wu J, He W, Wei Y, Chen H, Li J. Screening effective-component compatibility from Jinshui Chenfei formula for silicosis treatment by serum-pharmacochemistry and feedback system control. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2025; 138:156419. [PMID: 39884076 DOI: 10.1016/j.phymed.2025.156419] [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: 11/25/2024] [Revised: 01/12/2025] [Accepted: 01/21/2025] [Indexed: 02/01/2025]
Abstract
BACKGROUND The unclear chemical composition and mechanisms of action pose challenges for new drug development and quality control of traditional Chinese medicine (TCM) formulas. To address this, the concept of effective-component compatibility (ECC) was proposed to represent drug combination with equivalent efficacy to TCM formulas, along with clear composition and dosage. However, previous strategies for screening ECC have often overlooked the synergistic effects of its components. PURPOSE This study proposed a strategy integrating serum pharmacochemistry and feedback system control (FSC) to identify synergistic combinations as ECC of TCM formulas. The strategy was applied to identify the ECC of Jinshui Chenfei formula (JCF) for silicosis treatment. METHODS A chemical library of JCF was constructed using ultra-high-performance liquid chromatography-quadrupole extractive orbitrap mass spectrometry (UHPLC-Q-Extractive Orbitrap MS). The library was then used to identify absorbed prototype compounds of JCF, and the serum levels of its main components were analyzed. Based on the primary absorbed prototypes, FSC was employed to screen the most effective synergistic combinations from JCF for inhibiting LPS- and IL-4-induced macrophage polarization. The pharmacological effects of ECC-JCF were further validated using a silica-induced silicosis mouse model, and its synergistic mechanisms were investigated through transcriptomics and molecular dynamic simulations. RESULTS A total of 437 compounds were identified in JCF, with 203 absorbed prototypes detected following oral administration. After three rounds of FSC iterative screening, a synergistic combination of isoliquiritin (180 μg/ml/0.43 mM), glycyrrhizic acid (180 μg/ml/0.22 mM), and gallic acid (3.75 μg/ml/0.02 mM) significantly inhibited the expression of TNF-α, IL-1β, IL-6, CD206, and Arg-1 mRNA in mouse alveolar macrophages. This combination also protected lung tissues from alveolar collapse, inflammatory cell infiltration, fibroblast proliferation, and fibrous nodule formation. In addition, the combination improved alveolitis and fibrosis scores in silicosis mice, outperforming both the original JCF formula and the sum of individual components. The synergistic effects of these compounds may regulate targets in inflammation and fibrosis formation pathways. CONCLUSION This study identified an ECC of JCF with a well-defined composition and mechanism of action, facilitating the future development of JCF as a new drug. Compared with traditional ECC screening methods, this strategy reduces experimental workload while accounting for synergistic effects.
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Affiliation(s)
- Xinguang Liu
- Co-construction collaborative innovation center for Chinese medicine and respiratory diseases by Henan & education ministry of China, Henan University of Chinese Medicine, Zhengzhou, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
| | - Peng Zhao
- Co-construction collaborative innovation center for Chinese medicine and respiratory diseases by Henan & education ministry of China, Henan University of Chinese Medicine, Zhengzhou, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
| | - Liming Wang
- Co-construction collaborative innovation center for Chinese medicine and respiratory diseases by Henan & education ministry of China, Henan University of Chinese Medicine, Zhengzhou, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
| | - Jinyan Wu
- Co-construction collaborative innovation center for Chinese medicine and respiratory diseases by Henan & education ministry of China, Henan University of Chinese Medicine, Zhengzhou, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
| | - Wenrui He
- Co-construction collaborative innovation center for Chinese medicine and respiratory diseases by Henan & education ministry of China, Henan University of Chinese Medicine, Zhengzhou, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
| | - Yu Wei
- Co-construction collaborative innovation center for Chinese medicine and respiratory diseases by Henan & education ministry of China, Henan University of Chinese Medicine, Zhengzhou, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
| | - Hongrui Chen
- Co-construction collaborative innovation center for Chinese medicine and respiratory diseases by Henan & education ministry of China, Henan University of Chinese Medicine, Zhengzhou, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
| | - Jiansheng Li
- Co-construction collaborative innovation center for Chinese medicine and respiratory diseases by Henan & education ministry of China, Henan University of Chinese Medicine, Zhengzhou, China; Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China; Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
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Rojas I, de Mello MMM, Zanuzzo FS, Sandrelli RM, Peroni EDFC, Hall JR, Rise ML, Urbinati EC, Gamperl AK. Chronic hypoxia has differential effects on constitutive and antigen-stimulated immune function in Atlantic salmon ( Salmo salar). Front Immunol 2025; 16:1545754. [PMID: 40046052 PMCID: PMC11880259 DOI: 10.3389/fimmu.2025.1545754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Accepted: 02/03/2025] [Indexed: 05/13/2025] Open
Abstract
Chronic hypoxia events are a common occurrence in Atlantic salmon (Salmo salar) sea-cages, especially during the summer, and their frequency and severity are predicted to increase with climate change. Although hypoxia is considered a very important fish health and welfare issue by the aquaculture industry, few studies have investigated the impact of chronic hypoxia on the fish immune system and its response to pathogen exposure. We exposed post-smolt Atlantic salmon to hypoxia (40% air sat.) for 6 weeks. Thereafter, we sampled fish prior to (i.e., at Time 0, to assess constitutive immune function), and after they were intraperitoneally injected with PBS (phosphate buffered saline) or formalin-killed Aeromonas salmonicida. We measured several innate immune parameters including: hematological immune responses [respiratory burst (RB), hemolytic activity of alternate complement system and plasma lysozyme concentration], and the relative percentage of circulating blood cells (erythrocytes/immature erythrocytes, monocytes, and granulocytes and lymphocytes) at Time 0 and at 24 hours post-injection (hpi); and the transcript expression levels of 8 anti-bacterial biomarkers in the head kidney [interleukin-1 beta (il1b), interleukin-8a (il8a), cyclooxygenase-2 (cox2), toll-like receptor 5, secreted (strl5), CC chemokine-like 19b (ccl19b), serum amyloid A5 (saa5), hepcidin anti-microbial peptide a (hampa) and cathelicidin anti-microbial peptide b (campb)] at Time 0 and at 6 and 24 hpi. In addition, we measured serum immunoglobulin (IgM) levels at Time 0 and at 8 weeks post-injection (4 weeks after a 'boost' injection). Fish exposed to chronic hypoxia had greater numbers of monocytes, which was consistent with the increase in RB, plasma lysozyme concentration and upregulated head kidney anti-bacterial gene expression (i.e., campb, ccl19b, hampa, il8a, stlr5). In contrast, chronic hypoxia: reduced RB and leukocyte numbers at 24 hpi in Asal compared to PBS-injected fish, and the transcript levels of campb, il1b, saa5, il8a and stlr5 at 6- and/or 24- hpi; but had no effect on constitutive or post-stimulation serum IgM titers. Overall, our results indicate that chronic hypoxia has differential effects on salmon constitutive innate immune function vs. following antigen exposure, and thus, it is still unclear how chronic hypoxia will impact the capacity of fish to defend against pathogens.
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Affiliation(s)
- Isis Rojas
- Department of Ocean Sciences, Memorial University of Newfoundland, St. John’s, NL, Canada
| | - Mariana M. M. de Mello
- Aquaculture Center of Universidade Estadual Paulista (UNESP), São Paulo State University, Jaboticabal, São Paulo, Brazil
| | - Fábio S. Zanuzzo
- Department of Ocean Sciences, Memorial University of Newfoundland, St. John’s, NL, Canada
| | - Rebeccah M. Sandrelli
- Department of Ocean Sciences, Memorial University of Newfoundland, St. John’s, NL, Canada
| | | | - Jennifer R. Hall
- Aquatic Research Cluster, Core Research Equipment & Instrument Training Network (CREAIT) Network, Ocean Sciences Centre, Memorial University of Newfoundland, St. John’s, NL, Canada
| | - Matthew L. Rise
- Department of Ocean Sciences, Memorial University of Newfoundland, St. John’s, NL, Canada
| | - Elisabeth C. Urbinati
- Aquaculture Center of Universidade Estadual Paulista (UNESP), São Paulo State University, Jaboticabal, São Paulo, Brazil
| | - Anthony K. Gamperl
- Department of Ocean Sciences, Memorial University of Newfoundland, St. John’s, NL, Canada
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Li Y, Yu J, Zeng Z, Lin W. Regulation of ubiquitination in sepsis: from PAMP versus DAMP to peripheral inflammation and cell death. Front Immunol 2024; 15:1513206. [PMID: 39720715 PMCID: PMC11666442 DOI: 10.3389/fimmu.2024.1513206] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 11/25/2024] [Indexed: 12/26/2024] Open
Abstract
Sepsis (sepsis) is a systemic inflammatory response triggered by infection, and its pathologic features include overproduction of peripheral inflammatory factors (e.g., IL-1β, IL-6, TNF-α), which ultimately leads to cytokine storm and multiple organ dysfunction syndrome (MODS). Pathogen-associated molecular patterns (PAMP) and damage-associated molecular patterns (DAMP) induce strong immune responses and exacerbate inflammation by activating pattern recognition receptors (PRRs) in the host. Ubiquitination, as a key protein post-translational modification, dynamically regulates the activity of several inflammation-associated proteins (e.g., RIPK1, NLRP3) through the coordinated action of the E1, E2, and E3 enzymes, affects cell death pathways such as necroptosis and pyroptosis, and ultimately regulates the release of peripheral inflammatory factors. Deubiquitinating enzymes (DUBs), on the other hand, influence the intensity of the inflammatory response in sepsis by counter-regulating the ubiquitination process and balancing pro- and anti-inflammatory signals. This review focuses on how PAMP and DAMP activate inflammatory pathways via PRRs, and the central role of ubiquitination and deubiquitination in the development of sepsis, especially the mechanisms in regulating the secretion of peripheral inflammatory factors and cell death. By deeply dissecting the impact of the balance of ubiquitination and deubiquitination on inflammatory regulation, we further envision its potential as a therapeutic target in sepsis.
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Affiliation(s)
| | | | | | - Weixiong Lin
- Department of Anesthesiology I, Meizhou People’s Hospital,
Meizhou, Guangdong, China
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Rossi R, Medici F, Habberstad R, Klepstad P, Cilla S, Dall'Agata M, Kaasa S, Caraceni AT, Morganti AG, Maltoni M. Development of a predictive model for patients with bone metastases referred to palliative radiotherapy: Secondary analysis of a multicenter study (the PRAIS trial). Cancer Med 2024; 13:e70050. [PMID: 39390750 PMCID: PMC11467037 DOI: 10.1002/cam4.70050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Revised: 07/03/2024] [Accepted: 07/13/2024] [Indexed: 10/12/2024] Open
Abstract
BACKGROUND The decision to administer palliative radiotherapy (RT) to patients with bone metastases (BMs), as well as the selection of treatment protocols (dose, fractionation), requires an accurate assessment of survival expectancy. In this study, we aimed to develop three predictive models (PMs) to estimate short-, intermediate-, and long-term overall survival (OS) for patients in this clinical setting. MATERIALS AND METHODS This study constitutes a sub-analysis of the PRAIS trial, a longitudinal observational study collecting data from patients referred to participating centers to receive palliative RT for cancer-induced bone pain. Our analysis encompassed 567 patients from the PRAIS trial database. The primary objectives were to ascertain the correlation between clinical and laboratory parameters with the OS rates at three distinct time points (short: 3 weeks; intermediate: 24 weeks; prolonged: 52 weeks) and to construct PMs for prognosis. We employed machine learning techniques, comprising the following steps: (i) identification of reliable prognostic variables and training; (ii) validation and testing of the model using the selected variables. The selection of variables was accomplished using the LASSO method (Least Absolute Shrinkage and Selection Operator). The model performance was assessed using receiver operator characteristic curves (ROC) and the area under the curve (AUC). RESULTS Our analysis demonstrated a significant impact of clinical parameters (primary tumor site, presence of non-bone metastases, steroids and opioid intake, food intake, and body mass index) and laboratory parameters (interleukin 8 [IL-8], chloride levels, C-reactive protein, white blood cell count, and lymphocyte count) on OS. Notably, different factors were associated with the different times for OS with only IL-8 included both in the PMs for short- and long-term OS. The AUC values for ROC curves for 3-week, 24-week, and 52-week OS were 0.901, 0.767, and 0.806, respectively. CONCLUSIONS We successfully developed three PMs for OS based on easily accessible clinical and laboratory parameters for patients referred to palliative RT for painful BMs. While our findings are promising, it is important to recognize that this was an exploratory trial. The implementation of these tools into clinical practice warrants further investigation and confirmation through subsequent studies with separate databases.
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Affiliation(s)
- Romina Rossi
- Palliative Care UnitIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”MeldolaItaly
- Radiation Oncology, Department of Medical and Surgical Sciences (DIMEC)Alma Mater Studiorum University of BolognaBolognaItaly
| | - Federica Medici
- Radiation Oncology, Department of Medical and Surgical Sciences (DIMEC)Alma Mater Studiorum University of BolognaBolognaItaly
- Radiation OncologyIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Ragnhild Habberstad
- Department of Clinical and Molecular MedicineNorwegian University of Science and TechnologyTrondheimNorway
- Department of OncologySt. Olavs University HospitalTrondheimNorway
| | - Pal Klepstad
- Department of Circulation and Medical ImagingNorwegian University of Science and TechnologyTrondheimNorway
- Department of Anesthesiology and Intensive Care MedicineSt Olavs University HospitalTrondheimNorway
| | - Savino Cilla
- Medical Physics UnitResponsible Research HospitalCampobassoItaly
| | - Monia Dall'Agata
- Unit of Biostatistics and Clinical TrialsIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”MeldolaItaly
| | - Stein Kaasa
- Department of OncologyOslo University HospitalOsloNorway
| | - Augusto Tommaso Caraceni
- Palliative Care, Pain Therapy and Rehabilitation UnitFondazione IRCCS Istituto Nazionale dei TumoriMilanItaly
- Department of Clinical Sciences and Community HealthUniversità degli Studi di MilanoMilanItaly
| | - Alessio Giuseppe Morganti
- Radiation Oncology, Department of Medical and Surgical Sciences (DIMEC)Alma Mater Studiorum University of BolognaBolognaItaly
- Radiation OncologyIRCCS Azienda Ospedaliero‐Universitaria di BolognaBolognaItaly
| | - Marco Maltoni
- Medical Oncology Unit, Department of Medical and Surgical Sciences (DIMEC)Alma Mater Studiorum‐University of BolognaBolognaItaly
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8
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Jha A, Moore E. YIGSR, A Laminin-Derived Peptide, Dictates a Concentration-Dependent Impact on Macrophage Phenotype Response. Cell Mol Bioeng 2024; 17:423-440. [PMID: 39513005 PMCID: PMC11538123 DOI: 10.1007/s12195-024-00810-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Accepted: 06/18/2024] [Indexed: 11/15/2024] Open
Abstract
Purpose Macrophage immune cells play crucial roles in the inflammatory (M1) and regenerative (M2) processes. The extracellular matrix (ECM) composition, including presentation of embedded ligands, governs macrophage function. Laminin concentration is abundant in the basement membrane and is dependent on pathological state: reduced in inflammation and increased during regeneration. Distinct laminin ligands, such as IKVAV and YIGSR, have disparate roles in dictating cell function. For example, IKVAV, derived from the alpha chain of laminin, promotes angiogenesis and metastasis of cancer cells whereas YIGSR, beta chain derived, impedes angiogenesis and tumor progression. Previous work has demonstrated IKVAV's inflammation inhibiting properties in macrophages. Given the divergent role of IKVAV and YIGSR in interacting with cells through varied integrin receptors, we ask: what role does laminin derived peptide YIGSR play in governing macrophage function? Methods We quantified the influence of YIGSR on macrophage phenotype in 2D and 3D via immunostaining assessments for M1 marker inducible nitric oxide synthase (iNOS) and M2 marker Arginase-1 (Arg-1). We also analysed the secretome of human and murine macrophage response to YIGSR via a Luminex bead assay. Results YIGSR impact on macrophage phenotype occurs in a concentration-dependent manner. At lower concentrations of YIGSR, macrophage inflammation was increased whereas, at higher concentrations of YIGSR the opposite effect was seen within the same time frame. Secretomic assessments also demonstrate that pro-inflammatory chemokines and cytokines were increased at low YIGSR concentrations in M0, M1, M2 macrophages while pro-inflammatory secretion was reduced at higher concentrations. Conclusions YIGSR can be used as a tool to modulate macrophage inflammatory state within M1 and M2 phenotypes depending on the concentration of peptide. YIGSR's impact on macrophage function can be leveraged for the development of immunoengineering strategies in regenerative medicine and cancer therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s12195-024-00810-5.
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Affiliation(s)
- Aakanksha Jha
- Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742 USA
| | - Erika Moore
- Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742 USA
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9
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Huang Z, Chen LJ, Huang D, Yi J, Chen Z, Lin P, Wang Y, Zheng J, Chen W. Preoperative Intravitreal Conbercept Injection Reduced Both Angiogenic and Inflammatory Cytokines in Patients With Proliferative Diabetic Retinopathy. J Diabetes Res 2024; 2024:2550367. [PMID: 39308630 PMCID: PMC11416173 DOI: 10.1155/2024/2550367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 06/21/2024] [Accepted: 08/17/2024] [Indexed: 09/25/2024] Open
Abstract
Aims: To investigate the impact of intravitreal injection of conbercept, a recombinant fusion protein with decoy receptors for the vascular endothelial growth factor (VEGF) family, on intraocular concentrations of angiogenic and inflammatory mediators in patients with proliferative diabetic retinopathy (PDR), analyzed its potential impact on surgical outcomes. Methods: Forty eyes from 40 patients with PDR were included in this prospective study. Patients received intravitreal injection of conbercept followed by vitrectomy or phacovitrectomy in 1 week. Aqueous humor samples were collected before and 1 week after the conbercept injection. The concentrations of angiogenic and inflammatory cytokines and chemokines were measured by flow cytometry. Follow-up clinical data were collected and analyzed. Results: Intravitreal conbercept injection significantly decreased aqueous concentrations of VEGF (325.5 (baseline) versus 22.3 pg/mL (postinjection), p < 0.0001), PlGF (39.5 versus 24.5 pg/mL, p < 0.0001), and PDGF-A (54.1 versus 47.0 pg/mL, p = 0.0016), while no impact on bFGF levels. For inflammatory mediators, the concentration of TNF-α (0.79 versus 0.45 pg/mL, p = 0.0004) and IL-8 (180.6 versus 86 pg/mL, p < 0.0001) were decreased, while IL-6 (184.1 versus 333.7 pg/mL, p = 0.0003) and IL-10 (1.1 versus 1.5 pg/mL, p = 0.0032) were increased. No significant changes in IFN-γ or MCP-1 were detected. Three months after surgery, the mean best-corrected visual acuity improved from a baseline of 1.8 ± 0.1 logMAR to 0.7 ± 0.1 logMAR (p < 0.0001), with 36 eyes (90%) achieving an improvement of visual function. Conclusions: Intravitreal conbercept injection presents dual effects of antiangiogenesis and anti-inflammation and can be served as an adjuvant treatment to vitrectomy for PDR patients.
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Affiliation(s)
- Zijing Huang
- Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, Guangdong, China
| | - Li Jia Chen
- Department of Ophthalmology & Visual SciencesThe Chinese University of Hong Kong, Sha Tin, New Territories, Hong Kong
| | - Dingguo Huang
- Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, Guangdong, China
| | - Jingsheng Yi
- Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, Guangdong, China
| | - Zhiying Chen
- Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, Guangdong, China
- Fifth Clinical InstituteShantou University Medical College, Shantou, Guangdong, China
| | - Peimin Lin
- Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, Guangdong, China
| | - Yifan Wang
- Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, Guangdong, China
| | - Jianlong Zheng
- Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, Guangdong, China
| | - Weiqi Chen
- Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, Guangdong, China
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10
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Alotaibi BS, Hakami MA, Hazazi A, Alsaiari AA, Khalid M, Beg A. Investigating mechanistic insights of curcumin in blocking the Interleukin-8 signaling pathway associated with Breast Cancer: An in-silico approach. Saudi J Biol Sci 2024; 31:104035. [PMID: 38934013 PMCID: PMC11201349 DOI: 10.1016/j.sjbs.2024.104035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 05/25/2024] [Accepted: 05/28/2024] [Indexed: 06/28/2024] Open
Abstract
Interleukin-8 (IL-8) is a chemokine, a type of signaling molecule that has a role in immunological responses and inflammation. In recent years, IL-8 is additionally related to cancer growth and recurrence. Breast cancer growth, progression, and metastatic development are all linked to IL-8. Breast cancer cells are known to develop faster when IL-8 stimulates their proliferation and survival. It can also cause angiogenesis, or the creation of new blood vessels, which is necessary for tumor nutrition and growth. IL-8 and curcumin have been subjects of interest in drug design, particularly in the context of inflammation-related disorders and cancer. This study aims to give an overview of the role of IL-8. Inhibitor-based treatment approaches were being used to target IL-8 with curcumin. Molecular docking method was employed to find a potential interaction to supress competitive inhibition of IL-8 with curcumin. PASS analysis and ADMET characteristics were also being carried out. In the end, IL-8 complexed with curcumin is chosen for MD simulations. Overall, our results showed that during the simulation, the complex stayed comparatively stable. It is also possible to investigate curcumin further as a possible treatment option. The combined results imply that IL-8 and their genetic alterations can be studied in precision cancer therapeutic treatments, utilizing target-driven therapy and early diagnosis.
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Affiliation(s)
- Bader S. Alotaibi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Al- Quwayiyah-19257, Riyadh, Saudi Arabia
| | - Mohammed Ageeli Hakami
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Al- Quwayiyah-19257, Riyadh, Saudi Arabia
| | - Ali Hazazi
- Department of Pathology and Laboratory Medicine, Security Forces Hospital Program, Riyadh, Saudi Arabia
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Ahad Amer Alsaiari
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| | - Mohammad Khalid
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, P.O. Box 173, Al-Kharj 11942, Saudi Arabia
| | - Anam Beg
- Jamia Millia Islamia University, New Delhi, India
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11
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Ji J, Chen D, Ni J, Chang F. Research Advances in Vascular Remodeling in Choke Vessels of Perforator Flap: A Systematic Review. Ann Plast Surg 2024; 93:268-275. [PMID: 38775375 DOI: 10.1097/sap.0000000000003980] [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: 07/19/2024]
Abstract
BACKGROUND As a significant bridge between perforasomes, choke vessels are the key structure of blood supply expansion, also a prerequisite for preventing distal ischemic necrosis of the multiterritory perforator flap, where the remodeling of choke vessels after flap elevation plays an essential role. This systematic review highlights the underlying mechanisms and clinical ways to promote remodeling of choke vessels, as well as experimental observation approaches to further guide researchers. METHODS A systematic review was conducted from 1975 to 2023 through PubMed, EMBASE, Web of Science, and Cochrane database with the key words "choke vessels" and "perforator flap" to investigate the mechanisms and ways to promote remodeling of choke vessels as well as observation approaches. The inclusion criteria and exclusion criteria were set to screen the literature. RESULTS A total of 94 literatures were obtained through database retrieval. After removing the duplicate literature, reading the title and abstract, and reviewing the full text finally, 33 articles were included in the final study. CONCLUSIONS The underlying remodeling of choke vessels may be related to fluid shear stress, hypoxia, and inflammation. The clinical ways to promote remodeling of choke vessels include surgical delay, arterial supercharge, venous superdrainage, drugs, and stem cells. Various experimental methods of observing microvascular morphology allow for a comprehensive research of choke vessels.
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Affiliation(s)
- Jiahao Ji
- From the Department of Plastic and Burns Surgery, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, China
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12
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Xu YC, Wang QQ, Chen MY, Gao YJ, Wang JY, Ge HT, Weng H, Chen JP, Xu GH. The Effect of Gua Sha Therapy on Pain in Parkinson's Disease: a Randomized Controlled Trial. Int J Gen Med 2024; 17:2791-2800. [PMID: 38962174 PMCID: PMC11221773 DOI: 10.2147/ijgm.s461958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Accepted: 05/23/2024] [Indexed: 07/05/2024] Open
Abstract
Purpose Pain is a common yet undertreated symptom of Parkinson's disease (PD). This study investigated the effect of Gua Sha therapy on pain in patients with PD. Patients and Methods A total of 56 PD patients with pain were randomized into either the experimental group (n=28), receiving 12 sessions of Gua Sha therapy, or the control group (n=28) without additional treatment. Participants underwent assessment at baseline, after the twelfth invention, and at the 2-month follow-up timepoints. The primary outcome was KPPS and VAS. Secondary outcomes included UPDRS I-III, PDSS-2, HADS, PDQ-39, and blood biomarkers (5-HT, IL-8, IL-10). Results The experimental group reported a significant improvement in pain severity, motor functions, affective disorder, and sleep quality (P < 0.05). Furthermore, increasing trends in both 5-HT and IL-10, as well as decreasing trends in IL-8 were observed. No serious adverse events occurred. Conclusion The preliminary findings suggest that Gua Sha therapy may be effective and safe for alleviating pain and improving other disease-related symptoms in PD patients.
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Affiliation(s)
- Yu Chen Xu
- School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
| | - Qiu Qin Wang
- School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
| | - Meng Yuan Chen
- School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
| | - Yu Jie Gao
- School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
| | - Jia Yi Wang
- School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
| | - Hao Tian Ge
- School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
| | - Heng Weng
- School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
| | - Ju Ping Chen
- Department of Neurology, Changshu Hospital of Traditional Chinese Medicine, Suzhou, 215500, People’s Republic of China
| | - Gui Hua Xu
- School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China
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Vellingiri V, Balaji Ragunathrao VA, Joshi JC, Akhter MZ, Anwar M, Banerjee S, Dudek S, Tsukasaki Y, Pinho S, Mehta D. Endothelial ERG programs neutrophil transcriptome for sustained anti-inflammatory vascular niche. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.05.02.591799. [PMID: 38746216 PMCID: PMC11092576 DOI: 10.1101/2024.05.02.591799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/16/2024]
Abstract
Neutrophils (PMNs) reside as a marginated pool within the vasculature, ready for deployment during infection. However, how endothelial cells (ECs) control PMN extravasation and activation to strengthen tissue homeostasis remains ill-defined. Here, we found that the vascular ETS-related gene (ERG) is a generalized mechanism regulating PMN activity in preclinical tissue injury models and human patients. We show that ERG loss in ECs rewired PMN-transcriptome, enriched for genes associated with the CXCR2-CXCR4 signaling. Rewired PMNs compromise mice survival after pneumonia and induced lung vascular inflammatory injury following adoptive transfer into naïve mice, indicating their longevity and inflammatory activity memory. Mechanistically, EC-ERG restricted PMN extravasation and activation by upregulating the deubiquitinase A20 and downregulating the NFκB-IL8 cascade. Rescuing A20 in EC-Erg -/- endothelium or suppressing PMN-CXCR2 signaling rescued EC control of PMN activation. Findings deepen our understanding of EC control of PMN-mediated inflammation, offering potential avenues for targeting various inflammatory diseases. Highlights ERG regulates trans-endothelial neutrophil (PMN) extravasation, retention, and activationLoss of endothelial (EC) ERG rewires PMN-transcriptomeAdopted transfer of rewired PMNs causes inflammation in a naïve mouse ERG transcribes A20 and suppresses CXCR2 function to inactivate PMNs. In brief/blurb The authors investigated how vascular endothelial cells (EC) control polymorphonuclear neutrophil (PMN) extravasation, retention, and activation to strengthen tissue homeostasis. They showed that EC-ERG controls PMN transcriptome into an anti-adhesive and anti-inflammatory lineage by synthesizing A20 and suppressing PMNs-CXCR2 signaling, defining EC-ERG as a target for preventing neutrophilic inflammatory injury.
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14
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Wang F, Zhou F, Peng J, Chen H, Xie J, Liu C, Xiong H, Chen S, Xue G, Zhou X, Xie Y. Macrophage Tim-3 maintains intestinal homeostasis in DSS-induced colitis by suppressing neutrophil necroptosis. Redox Biol 2024; 70:103072. [PMID: 38330550 PMCID: PMC10865407 DOI: 10.1016/j.redox.2024.103072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 01/27/2024] [Accepted: 01/31/2024] [Indexed: 02/10/2024] Open
Abstract
T-cell immunoglobulin domain and mucin domain-3 (Tim-3) is a versatile immunomodulator that protects against intestinal inflammation. Necroptosis is a type of cell death that regulates intestinal homeostasis and inflammation. The mechanism(s) underlying the protective role of macrophage Tim-3 in intestinal inflammation is unclear; thus, we investigated whether specific Tim-3 knockdown in macrophages drives intestinal inflammation via necroptosis. Tim-3 protein and mRNA expression were assessed via double immunofluorescence staining and single-cell RNA sequencing (sc-RNA seq), respectively, in the colonic tissues of patients with inflammatory bowel disease (IBD) and healthy controls. Macrophage-specific Tim3-knockout (Tim-3M-KO) mice were generated to explore the function and mechanism of Tim-3 in dextran sodium sulfate (DSS)-induced colitis. Necroptosis was blocked by pharmacological inhibitors of receptor-interacting protein kinase (RIP)1, RIP3, and reactive oxygen species (ROS). Additionally, in vitro experiments were performed to assess the mechanisms of neutrophil necroptosis induced by Tim-3 knockdown macrophages. Although Tim-3 is relatively inactive in macrophages during colon homeostasis, it is highly active during colitis. Compared to those in controls, Tim-3M-KO mice showed increased susceptibility to colitis, higher colitis scores, and increased pro-inflammatory mediator expression. Following the administration of RIP1/RIP3 or ROS inhibitors, a significant reduction in intestinal inflammation symptoms was observed in DSS-treated Tim-3M-KO mice. Further analysis indicated the TLR4/NF-κB pathway in Tim-3 knockdown macrophages mediates the TNF-α-induced necroptosis pathway in neutrophils. Macrophage Tim-3 regulates neutrophil necroptosis via intracellular ROS signaling. Tim-3 knockdown macrophages can recruit neutrophils and induce neutrophil necroptosis, thereby damaging the intestinal mucosal barrier and triggering a vicious cycle in the development of colitis. Our results demonstrate a protective role of macrophage Tim-3 in maintaining gut homeostasis by inhibiting neutrophil necroptosis and provide novel insights into the pathogenesis of IBD.
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Affiliation(s)
- Fangfei Wang
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China; Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
| | - Feng Zhou
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China; Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
| | - Jianxiang Peng
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China; Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
| | - Hao Chen
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China; Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
| | - Jinliang Xie
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China; Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
| | - Cong Liu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China; Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
| | - Huifang Xiong
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China; Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
| | - Sihai Chen
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China; Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
| | - Guohui Xue
- Department of Clinical Laboratory, Affiliated Jiujiang Hospital of Nanchang University, Jiujiang, Jiangxi Province, China
| | - Xiaojiang Zhou
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China; Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China
| | - Yong Xie
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China; Institute of Digestive Disease, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China.
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15
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Takenoshita Y, Tokito A, Jougasaki M. Inhibitory Effects of Eicosapentaenoic Acid on Vascular Endothelial Growth Factor-Induced Monocyte Chemoattractant Protein-1, Interleukin-6, and Interleukin-8 in Human Vascular Endothelial Cells. Int J Mol Sci 2024; 25:2749. [PMID: 38473995 PMCID: PMC10931732 DOI: 10.3390/ijms25052749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 02/23/2024] [Accepted: 02/25/2024] [Indexed: 03/14/2024] Open
Abstract
Vascular endothelial growth factor (VEGF) induces monocyte chemoattractant protein-1 (MCP-1) and plays an important role in vascular inflammation and atherosclerosis. We investigated the mechanisms of VEGF-induced MCP-1 expression and the effects of eicosapentaenoic acid (EPA) in human umbilical vein endothelial cells (HUVECs). Real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) demonstrated that VEGF enhanced MCP-1 gene expression and protein secretion in HUVECs. Western immunoblot analysis revealed that VEGF induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and inhibitor of nuclear factor (NF)-κB (IκB). Treatment with pharmacological inhibitors of p38 MAPK (SB203580) or NF-κB (BAY11-7085) significantly suppressed VEGF-induced MCP-1 in HUVECs. EPA inhibited VEGF-induced MCP-1 mRNA, protein secretion, phosphorylation of p38 MAPK, and the translocation of phospho-p65 to the nucleus. Additionally, VEGF also stimulated gene expressions of interleukin (IL)-6 and IL-8, which were suppressed by SB203580, BAY11-7085, and EPA. The present study has demonstrated that VEGF-induced activation of MCP-1, IL-6, and IL-8 involves the p38 MAPK and NF-κB signaling pathways and that EPA inhibits VEGF-induced MCP-1, IL-6, and IL-8 via suppressing these signaling pathways. This study supports EPA as a beneficial anti-inflammatory and anti-atherogenic drug to reduce the VEGF-induced activation of proinflammatory cytokine and chemokines.
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Affiliation(s)
| | | | - Michihisa Jougasaki
- Institute for Clinical Research, NHO Kagoshima Medical Center, Kagoshima 892-0853, Japan; (Y.T.); (A.T.)
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16
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Shu Q, Zhang N, Liu Y, Wang X, Chen J, Xie H, Pan F, Zhao L, Ding X, Wen Y, Wang L, Xie W, Lu J, Su G, Peng H, Yang P. IL-8 Triggers Neutrophil Extracellular Trap Formation Through an Nicotinamide Adenine Dinucleotide Phosphate Oxidase- and Mitogen-Activated Protein Kinase Pathway-Dependent Mechanism in Uveitis. Invest Ophthalmol Vis Sci 2023; 64:19. [PMID: 37824136 PMCID: PMC10587853 DOI: 10.1167/iovs.64.13.19] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Accepted: 09/12/2023] [Indexed: 10/13/2023] Open
Abstract
Purpose To explore the mechanism underlying IL-8-induced neutrophil extracellular trap (NET) formation in patients with ocular-active Behçet's disease (BD) and the effect of inhibiting NET formation on the severity of inflammation in experimental autoimmune uveitis (EAU) mice. Methods The serum extracellular DNA and neutrophil elastase (NE) and IL-8 levels in patients with ocular-active BD, the expression of myeloperoxidase, NE, and histone H3Cit in IL-8-induced neutrophils isolated from healthy controls, and the effects of NETs on HMC3 cells were detected. Female C57BL/6J mice were immunized with IRBP651-670 to induce EAU and EAU mice received intravitreal injection of the CXCR2 (IL-8 receptor) antagonist SB225002 or PBS. The serum levels of extracellular DNA, NE, and keratinocyte-derived chemokine (the mouse ortholog of human IL-8) and expression of myeloperoxidase, NE, and histone H3Cit in mouse retinas were detected. Disease severity was evaluated by clinical and histopathological scores. Results Serum keratinocyte-derived chemokine expression levels in EAU mice and IL-8 expression levels in patients with ocular-active BD increased. IL-8 notably increased NET formation in a dose-dependent manner through an nicotinamide adenine dinucleotide phosphate oxidase and mitogen-activated protein kinase pathway dependent mechanism. IL-8-induced NET formation damaged HMC3 cells in vitro. Pretreatment with SB225002 notably ameliorated the production of NETs in EAU mice. Conclusions Our data confirm that NET formation is induced by IL-8. IL-8-induced NET formation was found to be related to mitogen-activated protein kinase and nicotinamide adenine dinucleotide phosphate pathways. Pretreatment with the CXCR2 antagonist SB225002 alleviated neutrophil infiltration and suppressed NET formation in EAU mice.
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Affiliation(s)
- Qinxin Shu
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Ni Zhang
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Yanyao Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xing Wang
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Jinquan Chen
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Hao Xie
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Fuying Pan
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Long Zhao
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Xuanheng Ding
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Yan Wen
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Lingda Wang
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Wenxi Xie
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Jing Lu
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Guannan Su
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Hui Peng
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
| | - Peizeng Yang
- The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, China
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Ma Y, Fu Y, Fan X, Ji Q, Duan X, Wang Y, Zhang Y, Wang Z, Hao H. FAK/IL-8 axis promotes the proliferation and migration of gastric cancer cells. Gastric Cancer 2023; 26:528-541. [PMID: 36959335 DOI: 10.1007/s10120-023-01384-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 03/10/2023] [Indexed: 03/25/2023]
Abstract
Gastric cancer (GC) is one of the most common malignancies in China and is associated with high mortality. The occurrence and development of gastric cancer are related to genetic and environmental factors. Focal adhesion kinase (FAK) is a cytoplasmic nonreceptor protein tyrosine kinase that is activated by the extracellular matrix and growth factors. FAK is highly expressed in cancer and promotes its development by regulating cancer cell proliferation, migration, and angiogenesis. The expression of IL-8 is increased in many types of malignant tumor cells and is linked to their proliferation, migration, invasion, angiogenesis, and EMT. In this study, we found FAK to be essential for the proliferation, migration, and peritoneal metastasis of gastric cancer cells. To examine the molecular regulatory mechanisms of FAK in the peritoneal dissemination of gastric cancer, we performed RNA-seq analysis of MKN-45-FAK-/- and MKN45 cells and demonstrated that IL-8 was downregulated in FAK-deficient cells. Conversely, we confirmed that IL-8 activates FAK activity. We established that IL-8 promotes the proliferation, colony formation, and migration of gastric cancer cells that are partially mediated by FAK. Thus, we propose that an IL-8-FAK-IL-8 positive feedback loop effects the proliferation and migration of gastric cancer cells.
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Affiliation(s)
- Yuze Ma
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, 24#Zhaojun Road, Hohhot, 010070, People's Republic of China
| | - Yu Fu
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, 24#Zhaojun Road, Hohhot, 010070, People's Republic of China
| | - Xiaoli Fan
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, 24#Zhaojun Road, Hohhot, 010070, People's Republic of China
| | - Qiang Ji
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, 24#Zhaojun Road, Hohhot, 010070, People's Republic of China
| | - XiaoJiao Duan
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, 24#Zhaojun Road, Hohhot, 010070, People's Republic of China
| | - Yanfeng Wang
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, 24#Zhaojun Road, Hohhot, 010070, People's Republic of China
| | - Yongmin Zhang
- Department of Chemistry and Chemical Engineering, Inner Mongolia University Research Center for Glycochemistry of Characteristic Medicinal Resources, Inner Mongolia University, 24#Zhaojun Road, Hohhot, 010070, People's Republic of China
| | - Zhigang Wang
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, 24#Zhaojun Road, Hohhot, 010070, People's Republic of China
| | - Huifang Hao
- State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, 24#Zhaojun Road, Hohhot, 010070, People's Republic of China.
- Department of Chemistry and Chemical Engineering, Inner Mongolia University Research Center for Glycochemistry of Characteristic Medicinal Resources, Inner Mongolia University, 24#Zhaojun Road, Hohhot, 010070, People's Republic of China.
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18
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Xie W, An L, Liu Z, Wang X, Fu X, Ma J. Therapeutic Effect of Polaprezinc on Reflux Esophagitis in the Rat Model. Dig Dis Sci 2023:10.1007/s10620-023-07990-6. [PMID: 37335414 DOI: 10.1007/s10620-023-07990-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 05/24/2023] [Indexed: 06/21/2023]
Abstract
BACKGROUND/AIMS To explore the protective effects and therapeutic mechanism of Esomeprazole (PPI), polaprezinc granule (PZ), and PPI + PZ on reflux esophagitis (RE) in the rat model. METHODS Wistar rats were randomly divided into 9 groups, which contain the control group, the acid cessation group (0.7% HCl, Q3D × 4), and the acid persistence group (0.7% HCl, Q3D × 11). PPI was administered by gavage at 8 mg·kg-1 body weight and PZ was administered by gavage at 120 mg·kg-1 body weight once a day for 15 days. The gastric cardia tissue of the feeding tube was observed under the light microscope, and the levels of interleukin-8 (IL-8) and prostaglandin E2 (PGE2) were measured by ELISA. The expression of EGFR, Akt, p-Akt, and p-mTOR was detected by Western blot. RESULTS The ELISA results showed that the levels of IL-8 and PGE2 were significantly increased in the model group, but decreased in all groups after treatment. In the acid cessation group, PZ treatment had the most significant effect on reducing IL-8 levels and PPI + PZ treatment had the most significant effect on reducing PGE2 levels. In the acid persistence group, the PPI treatment had the most significant effect on reducing the levels of IL-8 and PGE2, and the PZ treatment could also significantly reduce their levels, close to the normal value. Western blot results showed that the expression of PI3K/Akt/mTOR pathway protein was increased in the model group, while its expression was decreased after treatment. CONCLUSIONS Polaprezinc has a significant therapeutic effect on RE in rats, which can reduce the levels of IL-8 and PGE2 and downregulate the expression of PI3K/Akt/mTOR signal pathway protein. The efficacy of polaprezinc in the treatment of reflux esophagitis is comparable to that of PPI, and the combination of them is more effective in the reflux esophagitis treatment.
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Affiliation(s)
- Wenbo Xie
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130000, China
| | - Lu An
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130000, China
| | - Zhaoyang Liu
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Xindi Wang
- Liaoning University of Traditional Chinese Medicine, Shenyang, 110000, Liaoning Province, China
| | - Xueqi Fu
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130000, China
| | - Junfeng Ma
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130000, China.
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Watanabe H, Mokuda S, Tokunaga T, Kohno H, Ishitoku M, Araki K, Sugimoto T, Yoshida Y, Yamamoto T, Matsumoto M, Masumoto J, Hirata S, Sugiyama E. Expression of factor XIII originating from synovial fibroblasts and macrophages induced by interleukin-6 signaling. Inflamm Regen 2023; 43:2. [PMID: 36609460 PMCID: PMC9817275 DOI: 10.1186/s41232-022-00252-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 12/19/2022] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Blood coagulation factor XIII (FXIII) promotes cross-linking between fibrin molecules at the final stage of the blood coagulation cascade. However, its expression in cells or tissues and function, particularly factor XIII subunit B (FXIII-B), remains controversial. Hemorrhagic FXIII deficiency following anti-interleukin-6 (IL-6) receptor antibody treatment has been reported in patients with rheumatoid arthritis (RA). Patients receiving this biologics have reduced FXIII activity when compared to the activity in those treated with other biologics. The relationship between pro-inflammatory cytokines and FXIII expression remains unknown. METHODS To investigate the expression pattern of FXIII in synovial tissues, immunohistochemistry, RT-qPCR, and western blotting were performed. FXIII-A expressed monocyte-derived macrophages were treated with recombinant IL-6 and anti-IL-6 receptor antibody. RNA sequencing of FXIII-B-overexpressing cells was performed to clarify the function of FXIII-B. RESULTS The immunohistochemical analysis of synovial tissues revealed that factor XIII subunit A (FXIII-A) was expressed in M2 macrophages, and FXIII-B was expressed in fibroblast-like synoviocytes. IL-6 stimulation upregulated FXIII-A expression in IL-4-induced monocyte-derived macrophages, and the anti-IL-6 receptor antibody suppressed FXIII-A expression. FXIII-B was more abundantly secreted in the supernatant of fibroblast-like synoviocytes compared with that of other cells. RNA sequencing showed that FXIII-B elevated the expression of genes associated with anti-apoptotic molecules and chemokines. CONCLUSIONS Our findings highlight that synovial tissue is one of the sources of FXIII production. We also have demonstrated IL-6-dependent FXIII-A expression and the novel potential functions of FXIII-B.
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Affiliation(s)
- Hirofumi Watanabe
- grid.470097.d0000 0004 0618 7953Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551 Japan
| | - Sho Mokuda
- grid.470097.d0000 0004 0618 7953Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551 Japan
| | - Tadahiro Tokunaga
- grid.470097.d0000 0004 0618 7953Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551 Japan
| | - Hiroki Kohno
- grid.470097.d0000 0004 0618 7953Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551 Japan
| | - Michinori Ishitoku
- grid.470097.d0000 0004 0618 7953Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551 Japan
| | - Kei Araki
- grid.470097.d0000 0004 0618 7953Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551 Japan
| | - Tomohiro Sugimoto
- grid.470097.d0000 0004 0618 7953Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551 Japan
| | - Yusuke Yoshida
- grid.470097.d0000 0004 0618 7953Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551 Japan
| | - Toshihiro Yamamoto
- grid.255464.40000 0001 1011 3808Department of Pathology, Ehime University Proteo-Science Center and Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295 Japan
| | - Mayuko Matsumoto
- grid.255464.40000 0001 1011 3808Department of Pathology, Ehime University Proteo-Science Center and Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295 Japan
| | - Junya Masumoto
- grid.255464.40000 0001 1011 3808Department of Pathology, Ehime University Proteo-Science Center and Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295 Japan
| | - Shintaro Hirata
- grid.470097.d0000 0004 0618 7953Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551 Japan
| | - Eiji Sugiyama
- grid.470097.d0000 0004 0618 7953Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551 Japan
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Souissi C, Marzouki S, Elbini-Dhouib I, Jebali J, Oliveira F, Valenzuela JG, Srairi-Abid N, Kamhawi S, Ben Ahmed M. PpSP32, the Phlebotomus papatasi immunodominant salivary protein, exerts immunomodulatory effects on human monocytes, macrophages, and lymphocytes. Parasit Vectors 2023; 16:1. [PMID: 36593519 PMCID: PMC9806891 DOI: 10.1186/s13071-022-05627-7] [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: 10/31/2022] [Accepted: 12/19/2022] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND The saliva of sand flies, vectors of Leishmania parasites, contains several components that exert pharmacological activity facilitating the acquisition of blood by the insect and contributing to the establishment of infection. Previously, we demonstrated that PpSP32 is the immunodominant salivary antigen in humans exposed to Phlebotomus papatasi bites and validated its usefulness as a predictive biomarker of disease. PpSP32, whose functions are little known to date, is an intriguing protein due to its involvement in the etiopathogenesis of pemphigus, an auto-immune disease. Herein, we aimed to better decipher its role through the screening of several immunomodulatory activity either on lymphocytes or on monocytes/macrophages. METHODS Peripheral mononuclear cells from healthy volunteers were stimulated with anti-CD3/anti-CD28 antibodies, phytohemagglutinin, phorbol 12-myristate 13-acetate/ionomycin, or lipopolysaccharide in the presence of increasing doses of PpSP32. Cell proliferation was measured after the addition of tritiated thymidine. Monocyte activation was tested by analyzing the expression of CD86 and HLA-DR molecules by flow cytometry. Cytokine production was analyzed in culture supernatants by ELISA. THP-1-derived macrophages were stimulated with LPS in the presence of increasing doses of PpSP32, and cytokine production was analyzed in culture supernatants by ELISA and multiplex technique. The effect of PpSP32 on NF-kB signaling was tested by Western blot. The anti-inflammatory activity of PpSP32 was assessed in vivo in an experimental inflammatory model of carrageenan-induced paw edema in rats. RESULTS Our data showed that PpSP32 down-modulated the expression of activation markers in LPS-stimulated monocytes and THP1-derived macrophages. This protein negatively modulated the secretion of Th1 and Th2 cytokines by human lymphocytes as well as pro-inflammatory cytokines by monocytes, and THP1-derived macrophages. PpSP32 treatment led to a dose-dependent reduction of IκB phosphorylation. When PpSP32 was injected into the paw of carrageenan-injected rats, edema was significantly reduced. CONCLUSIONS Our data indicates that PpSP32 induces a potent immunomodulatory effect on monocytes and THP-1-derived macrophages. This inhibition could be mediated, among others, by the modulation of the NF-kB signaling pathway. The anti-inflammatory activity of PpSP32 was confirmed in vivo in the carrageenan-induced paw edema model in rats.
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Affiliation(s)
- Cyrine Souissi
- grid.418517.e0000 0001 2298 7385Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), LR11IPT02, Pasteur Institute de Tunis, Tunis, Tunisia
| | - Soumaya Marzouki
- grid.418517.e0000 0001 2298 7385Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), LR11IPT02, Pasteur Institute de Tunis, Tunis, Tunisia
| | - Ines Elbini-Dhouib
- grid.12574.350000000122959819Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El Manar, 1002 Tunis, Tunisia
| | - Jed Jebali
- grid.12574.350000000122959819Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El Manar, 1002 Tunis, Tunisia
| | - Fabiano Oliveira
- grid.94365.3d0000 0001 2297 5165Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, MD USA
| | - Jesus G. Valenzuela
- grid.94365.3d0000 0001 2297 5165Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, MD USA
| | - Najet Srairi-Abid
- grid.12574.350000000122959819Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El Manar, 1002 Tunis, Tunisia
| | - Shaden Kamhawi
- grid.94365.3d0000 0001 2297 5165Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, MD USA
| | - Melika Ben Ahmed
- grid.418517.e0000 0001 2298 7385Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), LR11IPT02, Pasteur Institute de Tunis, Tunis, Tunisia ,grid.12574.350000000122959819Faculty of Medicine de Tunis, University of Tunis El Manar, Tunis, Tunisia
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Yamashiro T, Kushibiki T, Mayumi Y, Tsuchiya M, Ishihara M, Azuma R. Negative-Pressure Wound Therapy: What We Know and What We Need to Know. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1436:131-152. [PMID: 36922487 DOI: 10.1007/5584_2023_773] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/17/2023]
Abstract
Negative-pressure wound therapy (NPWT) promotes wound healing by applying negative pressure to the wound surface. A quarter of a century after its introduction, NPWT has been used in various clinical conditions, although molecular biological evidence is insufficient due to delay in basic research. Here, we have summarized the history of NPWT, its mechanism of action, what is currently known about it, and what is expected to be known in the future. Particularly, attention has shifted from the four main mechanisms of NPWT to the accompanying secondary effects, such as effects on various cells, bacteria, and surgical wounds. This chapter will help the reader to understand the current status and shortcomings of NPWT-related research, which could aid in the development of basic research and, eventually, clinical use with stronger scientific evidence.
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Affiliation(s)
- Toshifumi Yamashiro
- Department of Plastic and Reconstructive Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Toshihiro Kushibiki
- Department of Medical Engineering, National Defense Medical College, Tokorozawa, Saitama, Japan.
| | - Yoshine Mayumi
- Department of Medical Engineering, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Masato Tsuchiya
- Department of Plastic and Reconstructive Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Miya Ishihara
- Department of Medical Engineering, National Defense Medical College, Tokorozawa, Saitama, Japan
| | - Ryuichi Azuma
- Department of Plastic and Reconstructive Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan
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Hu YJ, Song CS, Jiang N. Single nucleotide variations in the development of diabetic foot ulcer: A narrative review. World J Diabetes 2022; 13:1140-1153. [PMID: 36578869 PMCID: PMC9791576 DOI: 10.4239/wjd.v13.i12.1140] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 11/24/2022] [Accepted: 12/05/2022] [Indexed: 12/15/2022] Open
Abstract
Diabetes mellitus has become a global health problem, and the number of patients with diabetic foot ulcers (DFU) is rapidly increasing. Currently, DFU still poses great challenges to physicians, as the treatment is complex, with high risks of infection, recurrence, limb amputation, and even death. Therefore, a comprehensive understanding of DFU pathogenesis is of great importance. In this review, we summarized recent findings regarding the DFU development from the perspective of single-nucleotide variations (SNVs). Studies have shown that SNVs located in the genes encoding C-reactive protein, interleukin-6, tumor necrosis factor-alpha, stromal cell-derived factor-1, vascular endothelial growth factor, nuclear factor erythroid-2-related factor 2, sirtuin 1, intercellular adhesion molecule 1, monocyte chemoattractant protein-1, endothelial nitric oxide synthase, heat shock protein 70, hypoxia inducible factor 1 alpha, lysyl oxidase, intelectin 1, mitogen-activated protein kinase 14, toll-like receptors, osteoprotegerin, vitamin D receptor, and fibrinogen may be associated with the development of DFU. However, considering the limitations of the present investigations, future multi-center studies with larger sample sizes, as well as in-depth mechanistic research are warranted.
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Affiliation(s)
- Yan-Jun Hu
- Division of Orthopaedics and Traumatology, Department of Orthopaedics, Southern Medical University Nanfang Hospital, Guangzhou 510515, Guangdong Province, China
| | - Chen-Sheng Song
- Division of Orthopaedics and Traumatology, Department of Orthopaedics, Southern Medical University Nanfang Hospital, Guangzhou 510515, Guangdong Province, China
| | - Nan Jiang
- Division of Orthopaedics and Traumatology, Department of Orthopaedics, Southern Medical University Nanfang Hospital, Guangzhou 510515, Guangdong Province, China
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23
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Siniperca chuatsi Rhabdovirus (SCRV)-Induced Key Pathways and Major Antiviral Genes in Fish Cells. Microorganisms 2022; 10:microorganisms10122464. [PMID: 36557717 PMCID: PMC9788611 DOI: 10.3390/microorganisms10122464] [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: 11/04/2022] [Revised: 12/01/2022] [Accepted: 12/12/2022] [Indexed: 12/15/2022] Open
Abstract
Fish rhabdoviruses, including Siniperca chuatsi rhabdovirus (SCRV), are epidemic pathogens that harm fish aquaculture. To clarify the interactions between SCRV and its host and explore antiviral targets, the present study performed transcriptome analysis in a cultured S. chuatsi skin cell line (SCSC) after SCRV infection at 3, 12, 24, and 36 h post-infection (hpi). Comparison with control obtained 38, 353, 896, and 1452 differentially expressed genes (DEGs) in the detected time points, respectively. Further analysis of the Go terms and KEGG pathways revealed the key pathways "Cytokine-cytokine receptor interaction" and "interferon related pathways" in SCSC cells responding to SCRV infection. The significantly up-regulated genes in the pathways were also verified by qPCR. Furthermore, gene cloning and overexpression revealed that five interferon-stimulated genes (ISGs) IFI4407, IFI35, Viperin, IFIT1, and IFIT5 had the ability to inhibit SCRV replication in FHM (Fathead minnow) cells, especially an inhibition efficiency more than 50% was observed in IFI35 overexpressed cells. In summary, current study revealed the main innate immune pathways in S. chuatsi cells induced by SCRV infection and the major ISGs of S. chuatsi in controlling SCRV replication.
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Cheng J, Li Q, Xiao S, Nie L, Liao J, Jiang Q, Xiang B, Zhang H, Jiang Y, Yao C. The advanced lung cancer inflammation index predicts chemotherapy response and infection risk in multiple myeloma patients receiving induction chemotherapy. Front Genet 2022; 13:1047326. [PMID: 36425070 PMCID: PMC9678942 DOI: 10.3389/fgene.2022.1047326] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Accepted: 10/24/2022] [Indexed: 10/13/2023] Open
Abstract
Objective: This study aims to determine the clinical significance of the advanced lung cancer inflammation index (ALI) in predicting prognosis, chemotherapy response, and infection risk in newly diagnosed multiple myeloma (MM) patients receiving induction therapy. Methods: A retrospective analysis of the clinical characteristics and laboratory data of 111 newly diagnosed MM patients from the Haematology Department of the Third Xiangya Hospital of Central South University from January 2014 to March 2020 was performed. We first determined the relationship between ALI and overall survival (OS), as well as clinical and laboratory parameters. Second, predictive factors for chemotherapy response were analysed by univariate and multivariate regression analyses. Third, univariate regression analysis of risk factors was performed using infection as the evaluable outcome. Results: Of the 111 evaluable patients, the low ALI group (<32.7) exhibited significantly poorer survival than the high ALI group (51 months versus 77 months). Multivariable analysis showed that advanced age, chemotherapy response and serum calcium level were independent prognostic factors for OS. Better chemotherapy efficacy in the high ALI group (89.3%) than in the low ALI group (42.2%) (p < 0.001) was noted. Multivariate analysis suggested that only ALI [HR: 0.110, 95% CI (0.035-0.350), p = 0.000] is an independent predictive factor in evaluating the efficiency of induction chemotherapy. Forty patients (36.04%) presented with infection after induction chemotherapy. Univariate analysis suggested that low ALI and abnormal renal function increase risk of infection in newly diagnosed MM patients. Conclusion: Our study confirmed that ALI is not only a prognostic biomarker for newly diagnosed patients, but also predicts chemotherapy efficacy in newly diagnosed MM patients receiving induction therapy.
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Affiliation(s)
- Jie Cheng
- The Third Xiangya Hospital of Central South University, Changsha, China
| | - Qianyuan Li
- The Third Xiangya Hospital of Central South University, Changsha, China
| | - Sheng Xiao
- The Third Xiangya Hospital of Central South University, Changsha, China
| | - Lu Nie
- The Third Xiangya Hospital of Central South University, Changsha, China
| | - Jianping Liao
- The Third Xiangya Hospital of Central South University, Changsha, China
| | - Qingjie Jiang
- The Third Xiangya Hospital of Central South University, Changsha, China
| | - Biyu Xiang
- The Third Xiangya Hospital of Central South University, Changsha, China
| | - Hongfei Zhang
- The Third Xiangya Hospital of Central South University, Changsha, China
| | - Yanhong Jiang
- The Third Xiangya Hospital of Central South University, Changsha, China
| | - Chenjiao Yao
- The Third Xiangya Hospital of Central South University, Changsha, China
- The First Affiliated Hospital of Hainan Medical University, Haikou, China
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Wu Y, Shi Z, Chen J, Zhang H, Li M, Zhao Y, Shi H, Shi D, Guo L, Feng L. Porcine deltacoronavirus E protein induces interleukin-8 production via NF-κB and AP-1 activation. Vet Microbiol 2022; 274:109553. [PMID: 36181744 PMCID: PMC9428115 DOI: 10.1016/j.vetmic.2022.109553] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 08/22/2022] [Accepted: 08/27/2022] [Indexed: 11/23/2022]
Abstract
Infection induces the production of proinflammatory cytokines and chemokines such as interleukin-8 (IL-8) and interleukin-6 (IL-6). Although they facilitate local antiviral immunity, their excessive release leads to life-threatening cytokine release syndrome, exemplified by the severe cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the present study, we found that interleukin-8 (IL-8) was upregulated by PDCoV infection. We then demonstrated that PDCoV E protein induced IL-8 production and that the TM domain and the C-terminal domain of the E protein were important for IL-8 production. Subsequently, we showed here that deleting the AP-1 and NF-κB binding motif in porcine IL-8 promoter abrogated its activation, suggesting that IL-8 expression was dependent on AP-1 and NF-κB. Furthermore, PDCoV E induced IL-8 production, which was also dependent on the NF-κB pathway through activating nuclear factor p65 phosphorylation and NF-κB inhibitor alpha (IκBα) protein phosphorylation, as well as inducing the nuclear translocation of p65, eventually resulting in the promotion of IL-8 production. PDCoV E also activated c-fos and c-jun, both of which are members of the AP-1 family. These findings provide new insights into the molecular mechanisms of PDCoV-induced IL-8 production and help us further understand the pathogenesis of PDCoV infection.
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Affiliation(s)
- Yang Wu
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
| | - Zhaorong Shi
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
| | - Jianfei Chen
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
| | - Hongling Zhang
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
| | - Mingwei Li
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
| | - Ying Zhao
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
| | - Hongyan Shi
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
| | - Da Shi
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
| | - Longjun Guo
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
| | - Li Feng
- State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
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Li Z, Jiang B, Zhong Z, Cao J, Li H, Wang C, Li A. Skin transcriptomic analysis and immune-related gene expression of golden pompano (Trachinotus ovatus) after Amyloodinium ocellatum infection. FISH & SHELLFISH IMMUNOLOGY 2022; 128:188-195. [PMID: 35870749 DOI: 10.1016/j.fsi.2022.07.052] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 07/11/2022] [Accepted: 07/18/2022] [Indexed: 06/15/2023]
Abstract
Amyloodiniosis is a severe disease of marine and brackish water fish caused by Amyloodinium ocellatum. Golden pompano (Trachinotus ovatus) is often repeatedly infected by A. ocellatum, leading to extensive mortality. However, little is known about the immune response mechanisms of the T. ovatus following reinfection with A. ocellatum. In this study, an extensive analysis at the transcriptome level of T. ovatus skin was carried out at 24 h post-infection by A. ocellatum. During the transcriptomic analysis, 1367 differentially expressed genes (DEGs) in the skin of T. ovatus under A. ocellatum infection and control conditions were obtained. In Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotated analyses, the DEGs were significantly enriched in the immune-related pathways. To better understand the immune-related gene expression dynamics, a quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to assess the primary and secondary infection groups of T. ovatus at different stages (3 h, 12 h, 24 h, 48 h and, 72 h post-infection) of infection with A.ocellatum. The results showed that innate immunity-related genes [interleukin (IL-8), chemokine ligand 3 (CCL3), toll-like receptor 7 (TLR7), and G-type lysosome (LZM g)] and adaptive immunity-related gene [major histocompatibility complex (MHC) alpha antigen I and MHC alpha antigen II] expression levels in the primary and secondary infection groups were significantly increased compared to the control group. The expression of MHC I and MHC II was more rapidly upregulated in the secondary infection group compared with the primary infection group after A.ocellatum infection. However, no significant differences of A.ocellatum load were observed in primary and secondary infection groups. In addition, the serum of the primary infection group had significantly higher concentrations of triglyceride (TG), higher alanine transaminase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) activities than the control group. This study contributes to understanding the defense mechanisms in fish skin against ectoparasite infection.
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Affiliation(s)
- Zhicheng Li
- State Key Laboratory of Biocontrol/Guangdong Provincial Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals and Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, Guangdong, China
| | - Biao Jiang
- Innovative Institute of Animal Healthy Breeding, College of Animal Sciences and Technology, Zhongkai University of Agriculture and Engineering, Guangzhou, 510222, Guangdong, China
| | - Zhihong Zhong
- State Key Laboratory of Biocontrol/Guangdong Provincial Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals and Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, Guangdong, China
| | - Jizhen Cao
- State Key Laboratory of Biocontrol/Guangdong Provincial Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals and Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, Guangdong, China
| | - Han Li
- State Key Laboratory of Biocontrol/Guangdong Provincial Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals and Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, Guangdong, China
| | - Chenxi Wang
- State Key Laboratory of Biocontrol/Guangdong Provincial Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals and Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, Guangdong, China
| | - Anxing Li
- State Key Laboratory of Biocontrol/Guangdong Provincial Key Laboratory of Improved Variety Reproduction in Aquatic Economic Animals and Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, Guangdong, China.
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Ma X, Xu S, Li J, Cui L, Dong J, Meng X, Zhu G, Wang H. Selenomethionine protected BMECs from inflammatory injury and oxidative damage induced by Klebsiella pneumoniae by inhibiting the NF-κB and activating the Nrf2 signaling pathway. Int Immunopharmacol 2022; 110:109027. [PMID: 35820365 DOI: 10.1016/j.intimp.2022.109027] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/22/2022] [Accepted: 07/01/2022] [Indexed: 12/14/2022]
Abstract
Klebsiella pneumoniae (K. pneumoniae) is one of the main environmental pathogens causing bovine mastitis. The incidence of bovine mastitis caused by K. pneumoniae is increasing worldwide. Selenium is an essential trace element that has multiple physiological functions, such as antioxidant and anti-inflammatory activities. Therefore, this study aimed to verify whether selenomethionine (SeMet) could contribute to alleviating the inflammatory injury and oxidative damage induced by K. pneumoniae. Bovine mammary epithelial cells were cultured in vitro and pretreated with 4 μM SeMet before being infected with K. pneumoniae. Western blot analysis was used to detect the expression of the related proteins in the NF-κB and Nrf2 signaling pathways. The gene expression levels of IL-1β, IL-6, IL-8, TNF-α, Nrf2, Keap1, NQO-1 and HO-1 were detected using RT-qPCR. The levels of MDA, GSH-PX, SOD, CAT and T-AOC were detected by commercial assay kits. Flow cytometry was used to determine the level of intracellular ROS, and immunofluorescence was used to detect the nuclear localization of Nrf2 protein. Briefly, SeMet downregulated the phosphorylation levels of IκBα and p65 proteins and the gene expression levels of IL-1β, IL-6, IL-8 and TNF-α were also decreased. Moreover, the protein and gene expression levels of Nrf2, NQO-1 and HO-1 were upregulated, and the nuclear expression of Nrf2 protein was also promoted, which enhanced the activity of antioxidant enzymes. In conclusion, SeMet protected BMECs from inflammatory injury and oxidative stress induced by K. pneumoniae by inhibiting the NF-κB and activating the Nrf2 signaling pathway.
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Affiliation(s)
- Xiaomin Ma
- College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-innovation Center for Prevention and Control of Important Animal Infection Disease and Zoonoses, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou, Jiangsu 225009, China
| | - Siyan Xu
- College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-innovation Center for Prevention and Control of Important Animal Infection Disease and Zoonoses, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou, Jiangsu 225009, China
| | - Jianji Li
- College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-innovation Center for Prevention and Control of Important Animal Infection Disease and Zoonoses, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou, Jiangsu 225009, China
| | - Luying Cui
- College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-innovation Center for Prevention and Control of Important Animal Infection Disease and Zoonoses, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou, Jiangsu 225009, China
| | - Junsheng Dong
- College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-innovation Center for Prevention and Control of Important Animal Infection Disease and Zoonoses, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou, Jiangsu 225009, China
| | - Xia Meng
- College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-innovation Center for Prevention and Control of Important Animal Infection Disease and Zoonoses, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou, Jiangsu 225009, China
| | - Guoqiang Zhu
- College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-innovation Center for Prevention and Control of Important Animal Infection Disease and Zoonoses, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou, Jiangsu 225009, China.
| | - Heng Wang
- College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-innovation Center for Prevention and Control of Important Animal Infection Disease and Zoonoses, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou, Jiangsu 225009, China.
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He Y, Zou C, Cai Z. Construction and Comprehensive Analysis of the ceRNA Network to Reveal Key Genes for Benign Tracheal Stenosis. Front Genet 2022; 13:891741. [PMID: 35812753 PMCID: PMC9261475 DOI: 10.3389/fgene.2022.891741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 05/24/2022] [Indexed: 11/21/2022] Open
Abstract
Objective: To explore the possible biological functions of the differentially expressed genes in patients with benign tracheal stenosis, and to provide a valuable molecular basis for investigating the pathogenesis of benign tracheal stenosis. Method: Whole transcriptome sequencing was performed on blood samples collected from patients with benign tracheal stenosis and normal controls. Differentially expressed mRNA, lncRNA, and circRNA were analyzed using the DESeq2 package. The protein interaction networks for differentially expressed mRNAs were constructed by STRING. The results of gene co-expression network analysis, Starbase database prediction, and differential gene expression were combined to construct a competing endogenous RNA network. The transcription factors of key genes were predicted using the Network Analyst database and a transcription factor-mRNA regulatory network was constructed. The classical pathways, intermolecular interaction networks, and upstream regulatory components of key genes were analyzed using Ingenuity Pathway Analysis (IPA). Finally, the DGIDB database was used to predict the potential therapeutic drugs to target the identified key genes. Result: Based on mRNA, lncRNA and circRNA expression data, we found that differentially expressed mRNAs were enriched in oxygen transport, neutrophil activation, immune response, and oxygen binding. Then the pearson correlation between mRNAs of 46 key genes and lncRNAs and cricRNAs were calculated, and the correlation greater than 0.9 were selected to construct the co-expression network of “mRNA-lncRA” and “mRNA-cricRNA.” Moreover, a “lncRNA-miRNA-mRNA” network and a “circRNA-miRNA-mRNA” network were constructed. IPA analysis showed that the 46 key genes were significantly associated with inflammatory activation and acute respiratory distress syndrome. The constructed TF-mRNA regulatory network was composed of 274 nodes and 573 interacting pairs. 251 potential therapeutic drugs were identified from the DGIDB database. Conclusion: This study analyzed the differential genes associated with benign tracheal stenosis and explored the potential regulatory mechanisms, providing a scientific reference for further studies on the pathogenesis of benign tracheal stenosis.
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Affiliation(s)
- Yanpeng He
- The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Heibei Key Laboratory of Respiratory Critical Care, Shijiazhuang, China
- Department of Pulmonary and Critical Care Medicine, The First Hospital of Qinhuangdao, Qinhuangdao, China
| | - Chunyan Zou
- Department of Pulmonary and Critical Care Medicine, The First Hospital of Qinhuangdao, Qinhuangdao, China
| | - Zhigang Cai
- The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Heibei Key Laboratory of Respiratory Critical Care, Shijiazhuang, China
- *Correspondence: Zhigang Cai,
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Docando F, Nuñez-Ortiz N, Serra CR, Arense P, Enes P, Oliva-Teles A, Díaz-Rosales P, Tafalla C. Mucosal and systemic immune effects of Bacillus subtilis in rainbow trout (Oncorhynchus mykiss). FISH & SHELLFISH IMMUNOLOGY 2022; 124:142-155. [PMID: 35367376 DOI: 10.1016/j.fsi.2022.03.040] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 03/22/2022] [Accepted: 03/28/2022] [Indexed: 06/14/2023]
Abstract
Bacillus spp. are well known for their probiotic properties. Hence, the long-term feeding of Bacillus spp. strains to different fish species has been proved to confer beneficial effects regarding growth or pathogen resistance, among others. However, whether these strains could function as mucosal adjuvants, up-regulating immune responses after a single administration, has not yet been investigated in fish. Thus, in the current work, we have performed a series of experiments in rainbow trout (Oncorhynchus mykiss) aimed at establishing the potential of two Bacillus subtilis spore-forming strains, designated as ABP1 and ABP2, as oral adjuvants/immunostimulants. As an initial step, we evaluated their transcriptional effects on the rainbow trout intestinal epithelial cell line RTgutGC, and in gut tissue explants incubated ex vivo with the two strains. Their capacity to adhere to RTgutGC cells was also evaluated by flow cytometry. Although both strains had the capacity to modulate the transcription of several genes related to innate and adaptive immune responses, it was the ABP1 strain that led to stronger transcriptional effects, also exerting a higher binding capacity to intestinal epithelial cells. Consequently, we selected this strain to establish its effects on splenic B cells upon in vitro exposure as well as to determine the transcriptional effects exerted in the spleen, kidney, and gut after a single oral administration of the bacteria. Our results showed that B. subtilis ABP1 had the capacity to modulate the proliferation, IgM secreting capacity and MHC II surface expression of splenic B cells. Finally, we confirmed that this strain also induced the transcription of genes involved in inflammation, antimicrobial genes, and genes involved in T cell responses upon a single oral administration. Our results provide valuable information regarding how B. subtilis modulates the immune response of rainbow trout, pointing to the usefulness of the ABP1 strain to design novel oral vaccination strategies for aquaculture.
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Affiliation(s)
- F Docando
- Fish Immunology and Pathology Group, Animal Health Research Centre (CISA-INIA-CSIC), 28130, Valdeolmos-Alalpardo, Madrid, Spain; Autonomous University of Madrid, Madrid, Spain
| | - N Nuñez-Ortiz
- Fish Immunology and Pathology Group, Animal Health Research Centre (CISA-INIA-CSIC), 28130, Valdeolmos-Alalpardo, Madrid, Spain
| | - C R Serra
- Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos, S/N, 4450-208, Matosinhos, Portugal
| | - P Arense
- Fish Immunology and Pathology Group, Animal Health Research Centre (CISA-INIA-CSIC), 28130, Valdeolmos-Alalpardo, Madrid, Spain
| | - P Enes
- Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos, S/N, 4450-208, Matosinhos, Portugal; Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, Edifício FC4, 4169-007, Porto, Portugal
| | - A Oliva-Teles
- Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos, S/N, 4450-208, Matosinhos, Portugal; Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, Edifício FC4, 4169-007, Porto, Portugal
| | - P Díaz-Rosales
- Fish Immunology and Pathology Group, Animal Health Research Centre (CISA-INIA-CSIC), 28130, Valdeolmos-Alalpardo, Madrid, Spain.
| | - C Tafalla
- Fish Immunology and Pathology Group, Animal Health Research Centre (CISA-INIA-CSIC), 28130, Valdeolmos-Alalpardo, Madrid, Spain.
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Scheithauer L, Thiem S, Ünal CM, Dellmann A, Steinert M. Zinc Metalloprotease ProA from Legionella pneumophila Inhibits the Pro-Inflammatory Host Response by Degradation of Bacterial Flagellin. Biomolecules 2022; 12:624. [PMID: 35625552 PMCID: PMC9138289 DOI: 10.3390/biom12050624] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 04/08/2022] [Accepted: 04/09/2022] [Indexed: 01/27/2023] Open
Abstract
The environmental bacterium Legionella pneumophila is an intracellular pathogen of various protozoan hosts and able to cause Legionnaires' disease, a severe pneumonia in humans. By encoding a wide selection of virulence factors, the infectious agent possesses several strategies to manipulate its host cells and evade immune detection. In the present study, we demonstrate that the L. pneumophila zinc metalloprotease ProA functions as a modulator of flagellin-mediated TLR5 stimulation and subsequent activation of the pro-inflammatory NF-κB pathway. We found ProA to be capable of directly degrading immunogenic FlaA monomers but not the polymeric form of bacterial flagella. These results indicate a role of the protease in antagonizing immune stimulation, which was further substantiated in HEK-BlueTM hTLR5 Detection assays. Addition of purified proteins, bacterial suspensions of L. pneumophila mutant strains as well as supernatants of human lung tissue explant infection to this reporter cell line demonstrated that ProA specifically decreases the TLR5 response via FlaA degradation. Conclusively, the zinc metalloprotease ProA serves as a powerful regulator of exogenous flagellin and presumably creates an important advantage for L. pneumophila proliferation in mammalian hosts by promoting immune evasion.
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Affiliation(s)
- Lina Scheithauer
- Institut für Mikrobiologie, Technische Universität Braunschweig, Spielmannstr. 7, 38106 Braunschweig, Germany; (L.S.); (S.T.); (C.M.Ü.)
| | - Stefanie Thiem
- Institut für Mikrobiologie, Technische Universität Braunschweig, Spielmannstr. 7, 38106 Braunschweig, Germany; (L.S.); (S.T.); (C.M.Ü.)
| | - Can M. Ünal
- Institut für Mikrobiologie, Technische Universität Braunschweig, Spielmannstr. 7, 38106 Braunschweig, Germany; (L.S.); (S.T.); (C.M.Ü.)
| | - Ansgar Dellmann
- Institut für Pathologie, Städtisches Klinikum Braunschweig, Celler Straße 38, 38114 Braunschweig, Germany;
| | - Michael Steinert
- Institut für Mikrobiologie, Technische Universität Braunschweig, Spielmannstr. 7, 38106 Braunschweig, Germany; (L.S.); (S.T.); (C.M.Ü.)
- Helmholtz Center for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany
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Park S, Kim E, Kim G, Kim S, Choi Y, Paek D. What Activities in Forests Are Beneficial for Human Health? A Systematic Review. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:2692. [PMID: 35270397 PMCID: PMC8909949 DOI: 10.3390/ijerph19052692] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 02/22/2022] [Accepted: 02/23/2022] [Indexed: 12/14/2022]
Abstract
Over the past decade, clinical trials of forest-based interventions have increased, leading to their recognition as preventive medicine. However, little is known about the differences in health effects according to the activity characteristics of interventions. This study aimed to understand the types of activities and their associated health effects to identify differences in health effects between activities. PubMed, PsycINFO, Web of Science, and Scopus databases were searched, and methodological quality was assessed using Cochrane ROB2. A total of 32 randomized controlled trials (RCTs) met the eligibility criteria. Health outcomes were collected from 6264 participants aged 6-98 years, and the sample size was 12-585. The Interventions were walking (n = 21), staying (n = 7), exercise (n = 4), indirect exposure (n = 4), and the activity time was between 10 and 240 min. Overall, walking showed consistent positive health effects, and there were differences in effects on anxiety and depression, cognitive function, stress hormone, and inflammation according to the activity. However, most of the included studies had a high risk of bias, and interventions were limited to specific activities, durations, and frequencies. Although a few limitations remain, the findings in this study are of great significance in providing the basis for the design of forest-based interventions.
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Affiliation(s)
- Sujin Park
- Forest Human Service Division, Future Forest Strategy Department, National Institute of Forest Science, Seoul 02455, Korea; (S.P.); (E.K.); (G.K.); (S.K.); (Y.C.)
| | - Eunsoo Kim
- Forest Human Service Division, Future Forest Strategy Department, National Institute of Forest Science, Seoul 02455, Korea; (S.P.); (E.K.); (G.K.); (S.K.); (Y.C.)
| | - Geonwoo Kim
- Forest Human Service Division, Future Forest Strategy Department, National Institute of Forest Science, Seoul 02455, Korea; (S.P.); (E.K.); (G.K.); (S.K.); (Y.C.)
| | - Soojin Kim
- Forest Human Service Division, Future Forest Strategy Department, National Institute of Forest Science, Seoul 02455, Korea; (S.P.); (E.K.); (G.K.); (S.K.); (Y.C.)
| | - Yeji Choi
- Forest Human Service Division, Future Forest Strategy Department, National Institute of Forest Science, Seoul 02455, Korea; (S.P.); (E.K.); (G.K.); (S.K.); (Y.C.)
| | - Domyung Paek
- Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul 08826, Korea
- Institute of Health and Environment, Seoul National University, Seoul 08826, Korea
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Lee PT, Nan FH, Chiu PY, Tseng CC, Lee MC. Sarcodia suiae Water Extract Promotes the Expression of Proinflammatory and Th1-Type Cytokines and Delay the Onset of Mortality in Cobia (Rachycentron canadum) During Photobacterium damselae subsp. damselae Infection. Front Immunol 2022; 12:801501. [PMID: 35140710 PMCID: PMC8820276 DOI: 10.3389/fimmu.2021.801501] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 12/29/2021] [Indexed: 01/03/2023] Open
Abstract
Cobia (Rachycentron canadum) is a marine fish of high economic value that grows at a fast rate. However, intensive fish farming has led to disease outbreaks in cobia cultures, which is highly costly to the industry. The impact of infectious diseases on cobia production has led to the inappropriate and increased use of chemicals and antibiotics, which negatively affects the environment and human health and promotes the spread of drug-resistant pathogens. Hence, prophylactic measurements, such as the use of immunomodulators, are required to improve the health of cultured animals against pathogens. In this study, we examined the effects of Sarcodia suiae water extract (SSWE) in cobia in vitro and in vivo. We found that treatment with SSWE could significantly increase the expression of cytokines (e.g., IL-1β, IL-6, IL-10, IL-12, and TNF-α) and chemokines (e.g., IL-8) in primary cultured head kidney leukocytes. Intraperitoneal injection of SSWE (20 μg/g body weight) promoted higher expression of IL-6, IL-8, IL-10, IL-12, chemokines (e.g., CC1), and antibodies (e.g., IgT) in head kidney and spleen tissues of the fish compared with other dose levels. Additionally, we describe for the second time (only after India) of the isolation of Photobacterium damselae subsp. damselae (Phdd) from a deadly epizootic in cage-farmed cobia. An intraperitoneal inoculation of SSWE before Phdd challenge showed that SSWE treatment could delay the onset of mortality of cobia. Finally, fish that received SSWE intraperitoneally before infection with Phdd exhibited elevated expression of Th1-type cytokines, namely, IL-8, IL-12, TNF-α, and IFN-γ. At the same time, the expression of Th2-related factors (such as IL-10 in the head kidney, and IgM and IgT in the spleen) were lower for the fish that received SSWE instead of PBS before the Phdd challenge. The results indicate that SSWE treatment facilitates the induction of Th1-type cytokines in cobia to fight against Phdd infection and has the potential to be used as an immunostimulant and vaccine adjuvant for fish.
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Affiliation(s)
- Po-Tsang Lee
- Department of Aquaculture, National Taiwan Ocean University, Keelung City, Taiwan
| | - Fan-Hua Nan
- Department of Aquaculture, National Taiwan Ocean University, Keelung City, Taiwan
| | - Po-Yu Chiu
- Department of Aquaculture, National Taiwan Ocean University, Keelung City, Taiwan
| | - Chung-Chih Tseng
- Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung City, Taiwan
- Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung City, Taiwan
- *Correspondence: Chung-Chih Tseng, ; Meng-Chou Lee,
| | - Meng-Chou Lee
- Department of Aquaculture, National Taiwan Ocean University, Keelung City, Taiwan
- Center of Excellence for Ocean Engineering, National Taiwan Ocean University, Keelung City, Taiwan
- Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung City, Taiwan
- *Correspondence: Chung-Chih Tseng, ; Meng-Chou Lee,
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Bacteriophage-Resistant Salmonella rissen: An In Vitro Mitigated Inflammatory Response. Viruses 2021; 13:v13122468. [PMID: 34960737 PMCID: PMC8703591 DOI: 10.3390/v13122468] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/02/2021] [Accepted: 12/08/2021] [Indexed: 01/21/2023] Open
Abstract
Non-typhoid Salmonella (NTS) represents one of the major causes of foodborne diseases, which are made worse by the increasing emergence of antibiotic resistance. Thus, NTS are a significant and common public health concern. The purpose of this study is to investigate whether selection for phage-resistance alters bacterial phenotype, making this approach suitable for candidate vaccine preparation. We therefore compared two strains of Salmonella enterica serovar Rissen: RR (the phage-resistant strain) and RW (the phage-sensitive strain) in order to investigate a potential cost associated with the bacterium virulence. We tested the ability of both RR and RW to infect phagocytic and non-phagocytic cell lines, the activity of virulence factors associated with the main Type-3 secretory system (T3SS), as well as the canonic inflammatory mediators. The mutant RR strain-compared to the wildtype RW strain-induced in the host a weaker innate immune response. We suggest that the mitigated inflammatory response very likely is due to structural modifications of the lipopolysaccharide (LPS). Our results indicate that phage-resistance might be exploited as a means for the development of LPS-based antibacterial vaccines.
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Kim E, Park S, Kim S, Choi Y, Cho J, Cho SI, Chun HR, Kim G. Can Different Forest Structures Lead to Different Levels of Therapeutic Effects? A Systematic Review and Meta-Analysis. Healthcare (Basel) 2021; 9:1427. [PMID: 34828474 PMCID: PMC8623963 DOI: 10.3390/healthcare9111427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 10/19/2021] [Accepted: 10/19/2021] [Indexed: 11/24/2022] Open
Abstract
In recent decades, forests have expanded from natural resources for conservation and production to health-promoting resources. With the growing body of evidence supporting the therapeutic effects of forests, the number of investigations on the relationship between forest characteristics and therapeutic effects have increased. However, quantitative synthesis of primary studies has rarely been conducted due to a limited number of health studies including forest description and high heterogeneity of forest variables. In this study, we conducted a systematic review and meta-analysis to evaluate the relationship between the forest structure and the therapeutic effect. We systematically searched the studies examining the therapeutic effects of forests with different stand density and canopy density and synthesized the results. As a result of subgroup analysis, we found that stand density modifies the therapeutic effects. Emotional and cognitive restoration showed greatest improvement in low-density forests with a stand density of less than 500/ha and the therapeutic effects diminish as the stand density increases. The impact of canopy density was not found due to a lack of studies reporting canopy density. Although some limitations remain, the findings in this study have great significance in providing the basis for establishing management strategies of forests for therapeutic use.
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Affiliation(s)
- Eunsoo Kim
- Future Forest Strategy Department, Forest Human Service Division, National Institute of Forest Science, Seoul 02455, Korea; (E.K.); (S.P.); (S.K.); (Y.C.); (J.C.)
| | - Sujin Park
- Future Forest Strategy Department, Forest Human Service Division, National Institute of Forest Science, Seoul 02455, Korea; (E.K.); (S.P.); (S.K.); (Y.C.); (J.C.)
| | - Soojin Kim
- Future Forest Strategy Department, Forest Human Service Division, National Institute of Forest Science, Seoul 02455, Korea; (E.K.); (S.P.); (S.K.); (Y.C.); (J.C.)
| | - Yeji Choi
- Future Forest Strategy Department, Forest Human Service Division, National Institute of Forest Science, Seoul 02455, Korea; (E.K.); (S.P.); (S.K.); (Y.C.); (J.C.)
| | - Junghee Cho
- Future Forest Strategy Department, Forest Human Service Division, National Institute of Forest Science, Seoul 02455, Korea; (E.K.); (S.P.); (S.K.); (Y.C.); (J.C.)
| | - Sung-il Cho
- Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul 08826, Korea; (S.-i.C.); (H.-r.C.)
- Institute of Health and Environment, Seoul National University, Seoul 08826, Korea
| | - Hae-ryoung Chun
- Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul 08826, Korea; (S.-i.C.); (H.-r.C.)
| | - Geonwoo Kim
- Future Forest Strategy Department, Forest Human Service Division, National Institute of Forest Science, Seoul 02455, Korea; (E.K.); (S.P.); (S.K.); (Y.C.); (J.C.)
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Park S, Choi Y, Kim G, Kim E, Kim S, Paek D. Physiological and Psychological Assessments for the Establishment of Evidence-Based Forest Healing Programs. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:9283. [PMID: 34501872 PMCID: PMC8430466 DOI: 10.3390/ijerph18179283] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 08/26/2021] [Accepted: 08/29/2021] [Indexed: 11/16/2022]
Abstract
This study aimed to establish a health and medical foundation for forest healing programs and provide a basis for developing an evaluation system for such programs. While the number of visitors to forests and interest in forest healing effects are increasing, few studies have examined the various indicators of the persistent changes in forest healing effects. Therefore, this study conducted pre-, post-, and follow-up experiments on 87 health and clinical indicators in a sample of 88 adolescent participants. The relationships between pre-, post-, and follow-up experiment results for each indicator were analyzed. Of the 87 indicators, 46 showed significant changes, including systolic blood pressure, diastolic blood pressure, cholesterol, serotonin, vitamin D, CD16+CD56 count, interferon-γ, resilience, and self-esteem. The findings are significant for studying diverse participants and indicators and lay the foundation for developing forest healing programs by clarifying aspects such as the indicators suitable for short-term observation versus the indicators requiring long-term observation. Based on these analyses, the results of this study are expected to be useful when conducting research to establish an evidence-based forest healing program in the future.
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Affiliation(s)
- Sujin Park
- Future Forest Strategy Department, Forest Human Service Division, National Institute of Forest Science, Seoul 02455, Korea; (S.P.); (Y.C.); (G.K.); (E.K.); (S.K.)
- Graduate School of Public Health, Seoul National University, Seoul 08826, Korea
| | - Yeji Choi
- Future Forest Strategy Department, Forest Human Service Division, National Institute of Forest Science, Seoul 02455, Korea; (S.P.); (Y.C.); (G.K.); (E.K.); (S.K.)
| | - Geonwoo Kim
- Future Forest Strategy Department, Forest Human Service Division, National Institute of Forest Science, Seoul 02455, Korea; (S.P.); (Y.C.); (G.K.); (E.K.); (S.K.)
| | - Eunsoo Kim
- Future Forest Strategy Department, Forest Human Service Division, National Institute of Forest Science, Seoul 02455, Korea; (S.P.); (Y.C.); (G.K.); (E.K.); (S.K.)
| | - Soojin Kim
- Future Forest Strategy Department, Forest Human Service Division, National Institute of Forest Science, Seoul 02455, Korea; (S.P.); (Y.C.); (G.K.); (E.K.); (S.K.)
| | - Domyung Paek
- Graduate School of Public Health, Seoul National University, Seoul 08826, Korea
- Institute of Health and Environment, Seoul National University, Seoul 08826, Korea
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36
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AlAshqar A, Reschke L, Kirschen GW, Borahay MA. Role of inflammation in benign gynecologic disorders: from pathogenesis to novel therapies†. Biol Reprod 2021; 105:7-31. [PMID: 33739368 PMCID: PMC8256101 DOI: 10.1093/biolre/ioab054] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/15/2021] [Accepted: 03/17/2021] [Indexed: 12/16/2022] Open
Abstract
Emerging evidence supports the notion that inflammation fosters the development of common benign gynecologic disorders, including uterine leiomyoma, endometriosis, and adenomyosis. Numerous cytokines, chemokines, and growth and transcription factors have indisputable roles in the establishment and maintenance of benign gynecologic disorders by initiating complex cascades that promote proliferation, angiogenesis, and lesion progression. The interaction between inflammation and benign gynecologic disorders is orchestrated by a plethora of factors, including sex steroids, genetics, epigenetics, extracellular matrix, stem cells, cardiometabolic risk factors, diet, vitamin D, and the immune system. The role of inflammation in these disorders is not limited to local pathobiology but also extends to involve clinical sequelae that range from those confined to the reproductive tract, such as infertility and gynecologic malignancies, to systemic complications such as cardiovascular disease. Enhanced understanding of the intricate mechanisms of this association will introduce us to unvisited pathophysiological perspectives and guide future diagnostic and therapeutic implications aimed at reducing the burden of these disorders. Utilization of inflammatory markers, microRNA, and molecular imaging as diagnostic adjuncts may be valuable, noninvasive techniques for prompt detection of benign gynecologic disorders. Further, use of novel as well as previously established therapeutics, such as immunomodulators, hormonal treatments, cardiometabolic medications, and cyclooxygenase-2 and NF-κB inhibitors, can target inflammatory pathways involved in their pathogenesis. In this comprehensive review, we aim to dissect the existing literature on the role of inflammation in benign gynecologic disorders, including the proposed underlying mechanisms and complex interactions, its contribution to clinical sequelae, and the clinical implications this role entails.
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Affiliation(s)
- Abdelrahman AlAshqar
- Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, MD, USA
- Department of Obstetrics and Gynecology, Kuwait University, Kuwait City, Kuwait
| | - Lauren Reschke
- Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, MD, USA
| | - Gregory W Kirschen
- Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, MD, USA
| | - Mostafa A Borahay
- Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, MD, USA
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Lind A, Boraxbekk CJ, Petersen ET, Paulson OB, Andersen O, Siebner HR, Marsman A. Do glia provide the link between low-grade systemic inflammation and normal cognitive ageing? A 1 H magnetic resonance spectroscopy study at 7 tesla. J Neurochem 2021; 159:185-196. [PMID: 34142382 DOI: 10.1111/jnc.15456] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 06/04/2021] [Accepted: 06/15/2021] [Indexed: 02/06/2023]
Abstract
Low-grade systemic inflammation contributes to ageing-related cognitive decline, possibly by triggering a neuroinflammatory response through glial activation. Using proton magnetic resonance spectroscopy (1 H-MRS) at 7T in normal human individuals from 18 to 79 years in a cross-sectional study, we previously observed higher regional levels of myo-inositol (mIns), total creatine (tCr) and total choline (tCho) in older than younger age groups. Moreover, visuo-spatial working memory (vsWM) correlated negatively with tCr and tCho in anterior cingulate cortex (ACC) and mIns in hippocampus and thalamus. As mIns, tCr and tCho are higher in glia than neurons, this suggest a potential in vivo connection between cognitive ageing and higher regional levels of glia-related metabolites. In the present study, we tested whether these metabolic differences may be related to low-grade systemic inflammation. In the same individuals, plasma concentrations of the proinflammatory markers C-reactive protein (CRP), interleukin 8 (IL-8), and tumour necrosis factor α (TNF-α) were measured on the same day as 1 H-MRS assessments. We tested whether CRP, IL-8, and TNF-α concentrations correlated with the levels of glia-related metabolites. CRP and IL-8, but not TNF-α, were higher in older (69-79 years) than younger (18-26 years) individuals. CRP correlated positively with thalamic mIns and negatively with vsWM. IL-8 correlated positively with ACC tCho and hippocampal mIns, but not with vsWM. Mediation analysis revealed an indirect effect of IL-8 on vsWM via ACC tCho. Together, these findings corroborate the role of glial cells, perhaps via their role in neuroinflammation, as part of the neurobiological link between systemic inflammation and cognitive ageing.
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Affiliation(s)
- Anna Lind
- Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark
| | - Carl-Johan Boraxbekk
- Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark.,Department of Radiation Sciences, Umeå University, Umeå, Sweden.,Institute of Sports Medicine Copenhagen, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark
| | - Esben Thade Petersen
- Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark.,Center for Magnetic Resonance, Department of Health Technology, Technical University of Denmark, Kgs. Lyngby, Denmark
| | - Olaf Bjarne Paulson
- Neurobiology Research Unit, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Ove Andersen
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Clinical Research Centre, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark
| | - Hartwig Roman Siebner
- Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark.,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark
| | - Anouk Marsman
- Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark
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Bekeschus S, Clemen R, Haralambiev L, Niessner F, Grabarczyk P, Weltmann KD, Menz J, Stope M, von Woedtke T, Gandhirajan R, Schmidt A. The Plasma-Induced Leukemia Cell Death is Dictated by the ROS Chemistry and the HO-1/CXCL8 Axis. IEEE TRANSACTIONS ON RADIATION AND PLASMA MEDICAL SCIENCES 2021. [DOI: 10.1109/trpms.2020.3020686] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Gao J, Che D, Du X, Zheng Y, Jing H, Wang N. Imidazolidinyl urea activates mast cells via MRGPRX2 to induce non-histaminergic allergy. Toxicol Res (Camb) 2021; 10:467-475. [PMID: 34141160 DOI: 10.1093/toxres/tfab035] [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: 11/30/2020] [Revised: 03/16/2021] [Accepted: 03/25/2021] [Indexed: 11/13/2022] Open
Abstract
Imidazolidinyl urea (IU) is used as an antimicrobial preservative in cosmetic and pharmaceutical products. IU induces allergic contact dermatitis, however, the mechanism has not yet been elucidated. Mas-related G protein-coupled receptor-X2 (MRGPRX2) triggers drug-induced pseudo-allergic reactions. The aims of this study were to determine whether IU activated mast cells through MRGPRX2 to further trigger contact dermatitis. Wild-type (WT) and KitW-sh/HNihrJaeBsmJNju (MUT) mice were treated with IU to observe its effects on local inflammation and mast cells degranulation in vivo. Laboratory of allergic disease 2 cells were used to detect calcium mobilization and release of inflammatory mediators in vitro. WT mice showed a severe local inflammatory response and contact dermatitis, whereas only slight inflammatory infiltration was observed in MUT mice. Thus, MRGPRX2 mediated the IU-induced activation of mast cells. However, histamine, a typical allergen, was not involved in this process. Tryptase expressed by mast cells was the major non-histaminergic inflammatory mediator of contact dermatitis. IU induced anaphylactic reaction via MRGPRX2 and further triggering non-histaminergic contact dermatitis, which explained why antihistamines are clinically ineffective against some chronic dermatitis.
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Affiliation(s)
- Jiapan Gao
- Department of Pharmaceutical analysis, School of Pharmacy, Xi'an Jiaotong University, 76, Yanta west road, Xi'an, China
| | - Delu Che
- Department of Dermatology, Northwest Hospital, The Second Hospital Affiliated to Xi'an Jiaotong University, 157, Xiwu road, Xi'an, Shaanxi, China
| | - Xueshan Du
- Department of Dermatology, Northwest Hospital, The Second Hospital Affiliated to Xi'an Jiaotong University, 157, Xiwu road, Xi'an, Shaanxi, China
| | - Yi Zheng
- Department of Dermatology, Northwest Hospital, The Second Hospital Affiliated to Xi'an Jiaotong University, 157, Xiwu road, Xi'an, Shaanxi, China
| | - Huiling Jing
- Department of Dermatology, Xi'an Hospital of Traditional Chinese Medicine, 69, Fengcheng 8th Road, Xi'an, Shaanxi, China
| | - Nan Wang
- Department of Pharmaceutical analysis, School of Pharmacy, Xi'an Jiaotong University, 76, Yanta west road, Xi'an, China
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40
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Henkel J, Klauder J, Statz M, Wohlenberg AS, Kuipers S, Vahrenbrink M, Püschel GP. Enhanced Palmitate-Induced Interleukin-8 Formation in Human Macrophages by Insulin or Prostaglandin E 2. Biomedicines 2021; 9:biomedicines9050449. [PMID: 33919366 PMCID: PMC8143371 DOI: 10.3390/biomedicines9050449] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 04/10/2021] [Accepted: 04/18/2021] [Indexed: 02/07/2023] Open
Abstract
Macrophages in pathologically expanded dysfunctional white adipose tissue are exposed to a mix of potential modulators of inflammatory response, including fatty acids released from insulin-resistant adipocytes, increased levels of insulin produced to compensate insulin resistance, and prostaglandin E2 (PGE2) released from activated macrophages. The current study addressed the question of how palmitate might interact with insulin or PGE2 to induce the formation of the chemotactic pro-inflammatory cytokine interleukin-8 (IL-8). Human THP-1 cells were differentiated into macrophages. In these macrophages, palmitate induced IL-8 formation. Insulin enhanced the induction of IL-8 formation by palmitate as well as the palmitate-dependent stimulation of PGE2 synthesis. PGE2 in turn elicited IL-8 formation on its own and enhanced the induction of IL-8 release by palmitate, most likely by activating the EP4 receptor. Since IL-8 causes insulin resistance and fosters inflammation, the increase in palmitate-induced IL-8 formation that is caused by hyperinsulinemia and locally produced PGE2 in chronically inflamed adipose tissue might favor disease progression in a vicious feed-forward cycle.
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Affiliation(s)
- Janin Henkel
- Department of Nutritional Biochemistry, Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal, Germany; (J.K.); (M.S.); (A.-S.W.); (S.K.); (M.V.); (G.P.P.)
- Department of Nutritional Biochemistry, Faculty of Life Sciences: Food, Nutrition and Health, University of Bayreuth, D-95326 Kulmbach, Germany
- Correspondence: ; Tel.: +49-33200-885285
| | - Julia Klauder
- Department of Nutritional Biochemistry, Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal, Germany; (J.K.); (M.S.); (A.-S.W.); (S.K.); (M.V.); (G.P.P.)
| | - Meike Statz
- Department of Nutritional Biochemistry, Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal, Germany; (J.K.); (M.S.); (A.-S.W.); (S.K.); (M.V.); (G.P.P.)
| | - Anne-Sophie Wohlenberg
- Department of Nutritional Biochemistry, Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal, Germany; (J.K.); (M.S.); (A.-S.W.); (S.K.); (M.V.); (G.P.P.)
| | - Sonja Kuipers
- Department of Nutritional Biochemistry, Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal, Germany; (J.K.); (M.S.); (A.-S.W.); (S.K.); (M.V.); (G.P.P.)
| | - Madita Vahrenbrink
- Department of Nutritional Biochemistry, Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal, Germany; (J.K.); (M.S.); (A.-S.W.); (S.K.); (M.V.); (G.P.P.)
| | - Gerhard Paul Püschel
- Department of Nutritional Biochemistry, Institute of Nutritional Science, University of Potsdam, D-14558 Nuthetal, Germany; (J.K.); (M.S.); (A.-S.W.); (S.K.); (M.V.); (G.P.P.)
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IL-27 Protects the Brain from Ischemia-Reperfusion Injury via the gp130/STAT3 Signaling Pathway. J Mol Neurosci 2021; 71:1838-1848. [PMID: 33851350 DOI: 10.1007/s12031-021-01802-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 01/26/2021] [Indexed: 12/14/2022]
Abstract
The occurrence of ischemia-reperfusion (I/R) injury leads to dysfunction as well as high rates of morbidity and mortality in stroke, and new effective therapeutic strategies for I/R are still needed. We investigated the effect of IL-27 on I/R injury-induced neurological function impairment, cerebral infarction volume and variation in levels of inflammatory factors in mice with middle cerebral artery occlusion (MCAO), as well as concentration of LDH and neuronal apoptosis in a neuron oxygen-glucose deprivation and reperfusion (OGD/R) model mediated by gp130/STAT3 signaling in vitro. Our results indicated that IL-27 could bind to its receptor of gp130 to attenuate the I/R injury-induced impairment function and cerebral infarction volume, and decrease inflammatory cytokines TNF-α, IL-1β and MCP-1 but increase anti-inflammatory factors IL-10 and TGF-β in vivo, while inhibiting LDH leakage and neuronal apoptosis through activation of STAT3 to antagonize I/R induction. Our results suggest that IL-27 may protect the brain from I/R injury through the gp130/STAT3 signaling pathway.
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Lu Z, Zhang Y, Wang Y, Tan GH, Huang FY, Cao R, He N, Zhang L. A biotin-avidin-system-based virus-mimicking nanovaccine for tumor immunotherapy. J Control Release 2021; 332:245-259. [DOI: 10.1016/j.jconrel.2021.02.029] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 02/19/2021] [Accepted: 02/24/2021] [Indexed: 12/12/2022]
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43
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Pham TH, Cheng TC, Wang PC, Chen SC. Protective efficacy of four heat-shock proteins as recombinant vaccines against photobacteriosis in Asian seabass (Lates calcarifer). FISH & SHELLFISH IMMUNOLOGY 2021; 111:179-188. [PMID: 33556554 DOI: 10.1016/j.fsi.2021.02.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 01/26/2021] [Accepted: 02/02/2021] [Indexed: 06/12/2023]
Abstract
Photobacterium damselae subsp. piscicida (Phdp) is the causative agent of photobacteriosis in marine fish and is responsible for huge losses to marine aquaculture worldwide. Efforts have been made to develop a vaccine against this disease. Heat-shock proteins (HSPs) are a family of proteins that are ubiquitous in cellular life. Bacteria produce elevated levels of HSPs as a survival strategy when exposed to stressful environments in a host during infection. This group of proteins are also important antigens that can induce both humoral and cellular immune responses. In this study, four HSPs of Phdp, HSP90, HSP33, HSP70, and DnaJ, were selected for cloning and recombinant expression. Western blotting with rabbit anti-Phdp helped identify rHSP70 and rHSP33 as immunogenic proteins. Asian seabass (Lates calcarifer) immunised with rHSP90, rHSP33, rHSP70, and rDnaJ showed 48.28%, 62.07%, 51.72%, and 31.03% relative percent survival, respectively, after being challenged with Phdp strain AOD105021. High expression levels of immune-related genes and high antibody titres were observed in the rHSP33 group, and the sera of this group also exhibited a high level of bactericidal activity against Phdp. Collectively, our results suggest that HSP33 is a potential candidate for vaccine development against Phdp infection.
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Affiliation(s)
- Trung Hieu Pham
- International Degree Program of Ornamental Fish Technology and Aquatic Animal Health, International College, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan.
| | - Ta-Chih Cheng
- Department of Tropical Agriculture and International Cooperation, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan; Research Centre for Animal Biologics, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan.
| | - Pei-Chi Wang
- International Degree Program of Ornamental Fish Technology and Aquatic Animal Health, International College, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan; Department of Veterinary Medicine, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan; Southern Taiwan Fish Diseases Research Centre, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan.
| | - Shih-Chu Chen
- International Degree Program of Ornamental Fish Technology and Aquatic Animal Health, International College, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan; Department of Veterinary Medicine, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan; Southern Taiwan Fish Diseases Research Centre, College of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan; Research Centre for Animal Biologics, National Pingtung University of Science and Technology, Pingtung, 91201, Taiwan.
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Mawa PA, Hasso-Agopsowicz M, Lubyayi L, Nabakooza G, Nakibuule M, Blitz R, Dun L, Govind A, Kaleebu P, Webb EL, Elliott AM, Dockrell HM, Cose S, Smith SG. Immune Responses Following BCG Immunization of Infants in Uganda and United Kingdom Are Similar for Purified Protein Derivative but Differ for Secretory Proteins of Mycobacterium tuberculosis. Front Immunol 2021; 12:637114. [PMID: 33815390 PMCID: PMC8017231 DOI: 10.3389/fimmu.2021.637114] [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: 12/02/2020] [Accepted: 02/22/2021] [Indexed: 11/15/2022] Open
Abstract
Introduction: The immunogenicity of BCG vaccination in infants differs between populations. We hypothesized that prenatal exposure to mycobacterial antigens might explain the differences in immune responses to BCG seen in other studies of infants in Africa and the United Kingdom (UK) and we explored this in birth cohorts in Uganda and the UK. Materials and Methods: Blood samples were obtained from BCG-immunized infants of mothers with (n = 110) and without (n = 121) latent Mycobacterium tuberculosis infection (LTBI) in Uganda and BCG-immunized infants of mothers without LTBI (n = 25) in the UK at 10 and 52 weeks after birth. Cytokine and chemokine responses to PPD were measured to assess responses to BCG immunization, and to ESAT6/CFP10 to assess exposure to or infection with M. tuberculosis or non-tuberculous mycobacteria (NTM) in 6-day whole blood culture supernatants by a 17-plex Luminex assay. Median responses were compared between Ugandan infants (together, and separated by maternal LTBI status) and UK infants. Results: The IFN-γ response to BCG vaccination was similar between Ugandan and UK infants at 10 and 52 weeks. At week 52, TNF production was marginally higher in Ugandan infants, but after adjusting for multiple comparisons this difference was not significant. At weeks 10 and 52, stimulation of blood with ESAT6/CFP10 produced significantly higher IFN-γ, TNF, IL-12p40, IL-1α, IL-1β, IL-1Ra, IP-10, MIP-1α, MIP-1β, and GM-CSF in Ugandan compared to UK infants. Stimulation of blood with ESAT6/CFP10 produced significantly higher amounts of IL-8 (p = 0.0001), IL-10 (p = 0.0022), and IL-13 (p = 0.0020) in the UK than in Ugandan infants of mothers without LTBI at week 10, but not at week 52. Conclusions: Immune responses to mycobacterial antigens following BCG immunization are similar for PPD, but differ for ESAT6/CFP10, between infants in Uganda and the UK. Neither maternal LTBI nor infant exposure to or infection with mycobacteria impacts the response to BCG. The observed global differences in immune response to BCG immunization are likely to be due to other causes.
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Affiliation(s)
- Patrice A. Mawa
- Immunomodulation and Vaccines Programme, Medical Research Council-Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- Department of Immunology, Uganda Virus Research Institute, Entebbe, Uganda
- Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Mateusz Hasso-Agopsowicz
- Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Lawrence Lubyayi
- Immunomodulation and Vaccines Programme, Medical Research Council-Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- Department of Epidemiology and Biostatistics, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa
| | - Grace Nabakooza
- Immunomodulation and Vaccines Programme, Medical Research Council-Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | - Marjorie Nakibuule
- Immunomodulation and Vaccines Programme, Medical Research Council-Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | - Rose Blitz
- Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Li Dun
- Fetal Medicine Unit, Gynaecology and Obstetrics Department, North Middlesex University Hospital National Health Service Trust, London, United Kingdom
| | - Abha Govind
- Fetal Medicine Unit, Gynaecology and Obstetrics Department, North Middlesex University Hospital National Health Service Trust, London, United Kingdom
| | - Pontiano Kaleebu
- Immunomodulation and Vaccines Programme, Medical Research Council-Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- Department of Immunology, Uganda Virus Research Institute, Entebbe, Uganda
| | - Emily L. Webb
- Medical Research Council Tropical Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Alison M. Elliott
- Immunomodulation and Vaccines Programme, Medical Research Council-Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Hazel M. Dockrell
- Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Stephen Cose
- Immunomodulation and Vaccines Programme, Medical Research Council-Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Steven G. Smith
- Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom
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Influence of administration of mesenchymal stromal cell on pediatric oxygenator performance and inflammatory response. ACTA ACUST UNITED AC 2021; 5:99-107. [PMID: 33899029 PMCID: PMC8064572 DOI: 10.1016/j.xjon.2021.02.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Objective Mesenchymal stromal cells have important immunomodulatory and neuroprotective properties. The aim of this study was to evaluate the feasibility of mesenchymal stromal cell administration into a cardiopulmonary bypass (CPB) circuit, including a pediatric oxygenator, and to assess the immunomodulatory response of the circulating blood prime. Methods A bypass circuit with a pediatric oxygenator, including integral filter was primed with bank whole blood. Normal saline (control) or 120 × 106 mesenchymal stromal cells were injected into the venous reservoir after 80 minutes of perfusion. To assess oxygenator function, immune reaction, and cytokine/chemokine levels, the ex vivo circulation was maintained for 300 minutes after administration. Results There were no differences in flow rate, trans-oxygenator pressure gradient, blood oxygen, and carbon dioxide levels between control and cell delivery groups. No adhesion of mesenchymal stromal cells was observed on the filter mesh by scanning electron microscopy. Lymphocyte surface marker assay found no difference in the number of B cells, T cells, or natural killer cells between the 2 groups, indicating no immunogenicity of allogeneic mesenchymal stromal cells under ex vivo CPB conditions. CPB significantly changed the level of interleukin (IL) 4, IL-6, IL-8, IP-10, macrophage colony stimulating factor, macrophage inflammatory protein-1β, monocyte chemoattractant protein-1, and IL-1α over time. IL-6 level was significantly increased after cell administration. Conclusions The administration of mesenchymal stromal cells does not interfere with oxygenator function. Allogeneic mesenchymal stromal cells show no immunogenicity, and increase plasma IL-6 level during ex vivo circulation. Further investigation is necessary to determine the effect of mesenchymal stromal cell delivery through CPB during pediatric cardiac surgery.
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Probiotics Modulate Tilapia Resistance and Immune Response against Tilapia Lake Virus Infection. Pathogens 2020; 9:pathogens9110919. [PMID: 33172079 PMCID: PMC7694748 DOI: 10.3390/pathogens9110919] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 10/25/2020] [Accepted: 11/04/2020] [Indexed: 11/23/2022] Open
Abstract
Tilapia lake virus (TiLV) causes an emerging viral disease associated with high mortality and economic damage in tilapia farming around the world. The use of probiotics in aquaculture has been suggested as an alternative to antibiotics and drugs to reduce the negative impact of bacterial and viral infections. In this study, we investigate the effect of probiotic Bacillus spp. supplementation on mortality, viral load, and expression of immune-related genes in red hybrid tilapia (Oreochromis spp.) upon TiLV infection. Fish were divided into three groups, and fed with: control diet, 0.5% probiotics-supplemented diet, and 1% probiotics-supplemented diet. After 21 days of experimental feeding, the three groups were infected with TiLV and monitored for mortality and growth performances, while organs were sampled at different time points to measure viral load and the transcription modulation of immune response markers. No significant difference was found among the groups in terms of weight gain (WG), average daily gain (ADG), feed efficiency (FE), or feed conversion ratio (FCR). A lower cumulative mortality was retrieved from fish fed 0.5% and 1% probiotics (25% and 24%, respectively), compared to the control group (32%). Moreover, fish fed with 1% probiotic diet had a significantly lower viral load, than those fed with 0.5% probiotic and control diet at 5, 6, 9, and 12 days post infection-challenge (dpc). The expression patterns of immune-related genes, including il-8 (also known as CXCL8), ifn-γ, irf-3, mx, rsad-2 (also known as VIPERIN) showed significant upregulation upon probiotic treatment during the peak of TiLV pathogenesis (between 9 and 12 dpc) and during most of the study period in fish fed with 1% probiotics-supplemented diet. Taken together, these findings indicate that dietary supplementation using Bacillus spp. probiotics may have beneficial effects to strengthen tilapia immunity and resistance against TiLV infections. Therefore, probiotic treatments may be preventively administered to reduce losses caused by this emerging viral infection in tilapia aquaculture.
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Carriero MM, Henrique-Silva F, Meira CM, Gato IMQ, Caetano AR, Lobo FP, Alves AL, Varela ES, Maia AAM. Molecular characterization and gene expression analysis of the pro-inflammatory cytokines IL-1β and IL-8 in the South American fish Piaractus mesopotamicus challenged with Aeromonas dhakensis. Genet Mol Biol 2020; 43:e20200006. [PMID: 33174977 PMCID: PMC7687281 DOI: 10.1590/1678-4685-gmb-2020-0006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 08/06/2020] [Indexed: 11/24/2022] Open
Abstract
In the present study, the complete characterization of cDNA and genomic sequences of IL-1β and IL-8, as well as the expression profile of these genes in the South American fish pacu (Piaractus mesopotamicus) is provided. The full-length pmIL-1β cDNA was composed of 1208 nucleotides that would produce a precursor peptide with 273 amino acid residues. A putative caspase-1 cleavage site, similar to what is found in mammalian IL-1β, was identified producing a mature peptide with a theoretical molecular weight of 17.21 kDa. The pmIL-8 cDNA sequence consisted of 1019 nucleotides which encoded a 95-amino acid protein with a theoretical molecular weight of 10.43 kDa that showed all typical CXC chemokine features, including a 20-residue signal peptide and four conserved cysteine residues. Constitutive mRNA expression was detected for both genes in the liver, head kidney, gill, intestine, skin and spleen. After a bacterial challenge, up-regulation was detected for both pmIL-1β and pmIL-8 in the spleen and head kidney at 12 h post-infection. At 24 h post-infection there was a decrease in the expression of both genes, with pmIL-8 showing a significant down-regulation in the liver and head kidney when compared to the control groups.
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Affiliation(s)
- Mateus Maldonado Carriero
- Universidade de São Paulo, Faculdade de Zootecnia e Engenharia de Alimentos, Departamento de Medicina Veterinária, Pirassununga, SP, Brazil
| | - Flavio Henrique-Silva
- Universidade Federal de São Carlos, Departamento de Genética e Evolução, São Carlos, SP, Brazil
| | - Caroline Munhoz Meira
- Universidade de São Paulo, Faculdade de Zootecnia e Engenharia de Alimentos, Departamento de Medicina Veterinária, Pirassununga, SP, Brazil
| | - Igor Mateus Queiroz Gato
- Universidade de São Paulo, Faculdade de Zootecnia e Engenharia de Alimentos, Departamento de Medicina Veterinária, Pirassununga, SP, Brazil
| | - Alexandre Rodrigues Caetano
- Embrapa Recursos Genéticos e Biotecnologia, Empresa Brasileira de Pesquisa Agropecuária, Brasília, DF, Brazil
| | - Francisco Pereira Lobo
- Embrapa Informática na Agricultura, Empresa Brasileira de Pesquisa Agropecuária, Campinas, SP, Brazil
| | - Anderson Luis Alves
- Embrapa Pesca e Aquicultura, Empresa Brasileira de Pesquisa Agropecuária, Palmas, TO, Brazil
| | - Eduardo Sousa Varela
- Embrapa Pesca e Aquicultura, Empresa Brasileira de Pesquisa Agropecuária, Palmas, TO, Brazil
| | - Antonio Augusto Mendes Maia
- Universidade de São Paulo, Faculdade de Zootecnia e Engenharia de Alimentos, Departamento de Medicina Veterinária, Pirassununga, SP, Brazil
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Kim KI, Lee UH, Cho M, Jung SH, Min EY, Park JW. Transcriptome analysis based on RNA-seq of common innate immune responses of flounder cells to IHNV, VHSV, and HIRRV. PLoS One 2020; 15:e0239925. [PMID: 32986779 PMCID: PMC7521715 DOI: 10.1371/journal.pone.0239925] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 09/15/2020] [Indexed: 12/25/2022] Open
Abstract
Viral hemorrhagic septicemia virus (VHSV) and hirame rhabdovirus (HIRRV) belong to the genus Novirhabdovirus and are the causative agents of a serious disease in cultured flounder. However, infectious hematopoietic necrosis virus (IHNV), a prototype of the genus Novirhabdovirus, does not cause disease in flounder. To determine whether IHNV growth is restricted in flounder cells, we compared the growth of IHNV with that of VHSV and HIRRV in hirame natural embryo (HINAE) cells infected with novirhabdoviruses at 1 multiplicity of infection. Unexpectedly, we found that IHNV grew as well as VHSV and HIRRV. For successful growth in host cells, viruses modulate innate immune responses exerted by virus-infected cells. Our results suggest that IHNV, like VHSV and HIRRV, has evolved the ability to overcome the innate immune response of flounder cells. To determine the innate immune response genes of virus-infected HINAE cells which are commonly modulated by the three novirhabdoviruses, we infected HINAE cells with novirhabdoviruses at multiplicity of infection (MOI) 1 and performed an RNA sequencing-based transcriptome analysis at 24 h post-infection. We discovered ~12,500 unigenes altered by novirhabdovirus infection and found that many of these were involved in multiple cellular pathways. After novirhabdovirus infection, 170 genes involved in the innate immune response were differentially expressed compared to uninfected cells. Among them, 9 genes changed expression by more than 2-fold and were commonly modulated by all three novirhabdoviruses. Interferon regulatory factor 8 (IRF8), C-X-C motif chemokine receptor 1 (CXCR1), Toll/interleukin-1 receptor domain-containing adapter protein (TIRAP), cholesterol 25-hydroxylase (CH25H), C-X-C motif chemokine ligand 11, duplicate 5 (CXCL11.5), and Toll-like receptor 2 (TLR2) were up-regulated, whereas C-C motif chemokine receptor 6a (CCR6a), interleukin-12a (IL12a), and Toll-like receptor 1 (TLR1) were down-regulated. These genes have been reported to be involved in antiviral responses and, thus, their modulation may be critical for the growth of novirhabdovirus in flounder cells. This is the first report to identify innate immune response genes in flounder that are commonly modulated by IHNV, VHSV, and HIRRV. These data will provide new insights into how novirhabdoviruses survive the innate immune response of flounder cells.
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Affiliation(s)
- Kwang Il Kim
- Pathology Research Division, National Institute of Fisheries Science, Busan, Korea
| | - Unn Hwa Lee
- Department of Biological Sciences, University of Ulsan, Ulsan, Korea
| | - Miyoung Cho
- Pathology Research Division, National Institute of Fisheries Science, Busan, Korea
| | - Sung-Hee Jung
- Pathology Research Division, National Institute of Fisheries Science, Busan, Korea
| | - Eun Young Min
- Pathology Research Division, National Institute of Fisheries Science, Busan, Korea
| | - Jeong Woo Park
- Department of Biological Sciences, University of Ulsan, Ulsan, Korea
- * E-mail:
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Ren YR, Golding A, Sorbello A, Ji P, Chen J, Saluja B, Witzmann K, Arya V, Reynolds KS, Choi SY, Nikolov NP, Sahajwalla C. A Comprehensive Updated Review on SARS-CoV-2 and COVID-19. J Clin Pharmacol 2020; 60:954-975. [PMID: 32469437 PMCID: PMC7283834 DOI: 10.1002/jcph.1673] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 05/20/2020] [Indexed: 01/08/2023]
Abstract
This literature review aims to provide a comprehensive current summary of the pathogenesis, clinical features, disease course, host immune responses, and current investigational antiviral and immunomodulatory pharmacotherapies to facilitate the development of future therapies and measures for prevention and control.
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Affiliation(s)
- Yunzhao R Ren
- Division of Inflammation and Immune Pharmacology, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA
| | - Amit Golding
- Division of Rheumatology and Transplant Medicine, Office of Immunology and Inflammation, Office of New Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA
| | - Alfred Sorbello
- Office of Translational Sciences, Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA
| | - Ping Ji
- Division of Inflammation and Immune Pharmacology, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA
| | - Jianmeng Chen
- Division of Inflammation and Immune Pharmacology, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA
| | - Bhawana Saluja
- Division of Inflammation and Immune Pharmacology, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA
| | - Kimberly Witzmann
- Office of Bioequivalence, Office of Generic Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA
| | - Vikram Arya
- Division of Infectious Disease Pharmacology, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA
| | - Kellie S Reynolds
- Division of Infectious Disease Pharmacology, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA
| | - Su-Young Choi
- Division of Infectious Disease Pharmacology, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA
| | - Nikolay P Nikolov
- Division of Rheumatology and Transplant Medicine, Office of Immunology and Inflammation, Office of New Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA
| | - Chandrahas Sahajwalla
- Division of Inflammation and Immune Pharmacology, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, USA
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Choi H, Kim Y, Mirzaaghasi A, Heo J, Kim YN, Shin JH, Kim S, Kim NH, Cho ES, In Yook J, Yoo TH, Song E, Kim P, Shin EC, Chung K, Choi K, Choi C. Exosome-based delivery of super-repressor IκBα relieves sepsis-associated organ damage and mortality. SCIENCE ADVANCES 2020; 6:eaaz6980. [PMID: 32285005 PMCID: PMC7141819 DOI: 10.1126/sciadv.aaz6980] [Citation(s) in RCA: 148] [Impact Index Per Article: 29.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Accepted: 01/13/2020] [Indexed: 05/18/2023]
Abstract
As extracellular vesicles that play an active role in intercellular communication by transferring cellular materials to recipient cells, exosomes offer great potential as a natural therapeutic drug delivery vehicle. The inflammatory responses in various disease models can be attenuated through introduction of super-repressor IκB (srIκB), which is the dominant active form of IκBα and can inhibit translocation of nuclear factor κB into the nucleus. An optogenetically engineered exosome system (EXPLOR) that we previously developed was implemented for loading a large amount of srIκB into exosomes. We showed that intraperitoneal injection of purified srIκB-loaded exosomes (Exo-srIκBs) attenuates mortality and systemic inflammation in septic mouse models. In a biodistribution study, Exo-srIκBs were observed mainly in the neutrophils, and in monocytes to a lesser extent, in the spleens and livers of mice. Moreover, we found that Exo-srIκB alleviates inflammatory responses in monocytic THP-1 cells and human umbilical vein endothelial cells.
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Affiliation(s)
- Hojun Choi
- Department of Bio and Brain Engineering, KAIST, Daejeon 34141, Republic of Korea
- Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Republic of Korea
| | - Youngeun Kim
- ILIAS Biologics Inc., Daejeon 34014, Republic of Korea
| | - Amin Mirzaaghasi
- Department of Bio and Brain Engineering, KAIST, Daejeon 34141, Republic of Korea
| | - Jaenyoung Heo
- ILIAS Biologics Inc., Daejeon 34014, Republic of Korea
| | - Yu Na Kim
- ILIAS Biologics Inc., Daejeon 34014, Republic of Korea
| | - Ju Hye Shin
- Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Seonghun Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Nam Hee Kim
- Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 03722, Republic of Korea
| | - Eunae Sandra Cho
- Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 03722, Republic of Korea
| | - Jong In Yook
- Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul 03722, Republic of Korea
| | - Tae-Hyun Yoo
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Eunjoo Song
- IVIM Technology, Daejeon 34051, Republic of Korea
| | - Pilhan Kim
- Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Republic of Korea
- IVIM Technology, Daejeon 34051, Republic of Korea
- Graduate School of Nanoscience and Technology, KAIST, Daejeon 34141, Republic of Korea
| | - Eui-Cheol Shin
- Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Republic of Korea
- Corresponding author. (K.Cho.); (E.-C.S.); (K.Chu.)
| | - Kyungsoo Chung
- Division of Pulmonology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
- Corresponding author. (K.Cho.); (E.-C.S.); (K.Chu.)
| | - Kyungsun Choi
- ILIAS Biologics Inc., Daejeon 34014, Republic of Korea
- Corresponding author. (K.Cho.); (E.-C.S.); (K.Chu.)
| | - Chulhee Choi
- Department of Bio and Brain Engineering, KAIST, Daejeon 34141, Republic of Korea
- Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Republic of Korea
- ILIAS Biologics Inc., Daejeon 34014, Republic of Korea
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