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Bozyel B, Doğan Ö, Elgün S, Özdemir B. Hypoxic Responses in Periodontal Tissues: Influence of Smoking and Periodontitis. J Clin Periodontol 2025; 52:249-257. [PMID: 39491490 PMCID: PMC11743020 DOI: 10.1111/jcpe.14087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Revised: 10/01/2024] [Accepted: 10/15/2024] [Indexed: 11/05/2024]
Abstract
AIM This study aimed to investigate the hypoxic changes in periodontal tissues resulting from smoking and periodontitis by assessing levels of hypoxia-inducible factors (HIF-1α, HIF-2α, HIF-3α) and vascular endothelial growth factor (VEGF) in gingival crevicular fluid (GCF). MATERIALS AND METHODS The study comprised 22 periodontally healthy non-smokers (Group H), 22 periodontally healthy smokers (Group HS), 22 non-smokers with periodontitis (Group P) and 22 smokers with periodontitis (Group PS). Clinical periodontal parameters were documented, and GCF samples were collected and analysed using enzyme-linked immunosorbent assay (ELISA). RESULTS Significantly elevated levels of HIF-1α, HIF-3α and VEGF were observed in Groups HS, P and PS compared to Group H (p < 0.05). Moreover, higher HIF-2α levels were detected in the Groups HS and P compared to Group H (p < 0.05). Significant correlations were detected between all evaluated hypoxia biomarkers in the Group P (p < 0.05) except HIF-2α and HIF-3α. However, in the PS group, significant correlation appeared only between HIF-1α and HIF-2α (p < 0.05). CONCLUSION Our findings indicate that smoking and periodontitis induce comparable hypoxic effects in periodontal tissues, as evidenced by the evaluated biomarkers. Further research is warranted to gain a deeper understanding of the mechanisms underlying hypoxia in periodontal tissues.
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Affiliation(s)
- Bejna Bozyel
- Department of PeriodontologyFaculty of Dentistry, Gazi UniversityAnkaraTurkey
| | - Özlem Doğan
- Department of Medical BiochemistryFaculty of Medicine, Ankara UniversityAnkaraTurkey
| | - Serenay Elgün
- Department of Medical BiochemistryFaculty of Medicine, Ankara UniversityAnkaraTurkey
| | - Burcu Özdemir
- Department of PeriodontologyFaculty of Dentistry, Gazi UniversityAnkaraTurkey
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Luan X, Zhu D, Hao Y, Xie J, Wang X, Li Y, Zhu J. Qibai Pingfei Capsule ameliorated inflammation in chronic obstructive pulmonary disease (COPD) via HIF-1 α/glycolysis pathway mediated of BMAL1. Int Immunopharmacol 2025; 144:113636. [PMID: 39579541 DOI: 10.1016/j.intimp.2024.113636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 11/08/2024] [Accepted: 11/11/2024] [Indexed: 11/25/2024]
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) is characterized for the persistent inflammation. The brain and muscle arnt-like 1 (BMAL1), as a crucial clock gene, is associated with the expression level of upstream factor hypoxia-inducible factor (HIF)-1α in glycolysis, which may affect the occurrence of inflammatory reactions in COPD. However, the moderation effect of Qibai Pingfei Capsule (QBPF) capsule is still unknown on BMAL1 and HIF-1α/glycolytic pathway. OBJECTIVE The aim of this study is to investigate the modulatory effects of QBPF capsules on BMAL1 and the HIF-1α/glycolytic pathway in COPD. METHODS The multifactorial approach were used to construct the COPD rat model, including forced swimming, hypoxia, and inhalation of cigarette smoke with four weeks. Nextly, the rats received a two-week course of gavage treatment with medicant. Finally, tissue samples were collected for comprehensive analysis using various molecular biology techniques. These methods included molecular docking, immunoprecipitation, small interfering RNA (siRNA), hematoxylin and eosin (HE) staining, western blot (WB), and immunofluorescence etc. to elucidate the modulatory effects of QBPF for treating COPD in vitro and in vivo. RESULTS The expression levels in mRNA and protein of BMAL1 decreased in COPD, while the content in mRNA and protein of HIF-1α increased. At the same time, the concentration in glycolytic metabolites of hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), lactate dehydrogenase (LDH), and lactate (LD) increased, and ATP decreased. The QBPF capsule can reverse the imbalance between BMAL1 and HIF-1α, improve disorders of glycolytic pathway, and alleviate the inflammation response. Notably, in vivo experiments, the interaction between BMAL1 and HIF-1α were confirmed via molecular docking and immunoprecipitation. In rescue experiments, intervention with siRNA BMAL1 in 16HBE cells revealed a significant decrease in BMAL1 levels and the therapeutic effect of QBPF was also affected. CONCLUSION QBPF could up-regulate the expression level of clock gene BMAL1, thereby regulating the HIF-1α/glycolytic pathway and metabolite to improve the inflammatory response in COPD.
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Affiliation(s)
- Xuejing Luan
- College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China
| | - Dandan Zhu
- Research Center of Integrated Traditional Chinese and Western Medicine, Wannan Medical College, Wuhu 241002, China
| | - Yifei Hao
- Research Center of Integrated Traditional Chinese and Western Medicine, Wannan Medical College, Wuhu 241002, China
| | - Jinghui Xie
- College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China
| | - Xiu Wang
- Research Center of Integrated Traditional Chinese and Western Medicine, Wannan Medical College, Wuhu 241002, China
| | - Yan Li
- Yijishan Hospital Affiliated to Wannan Medical College, Wuhu 241001, China
| | - Jie Zhu
- College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, China; Research Center of Integrated Traditional Chinese and Western Medicine, Wannan Medical College, Wuhu 241002, China.
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Nag DS, Varghese K, Swain A, Patel R, Sahu S, Sam M. Update on the aetiopathogenesis of obstructive sleep apnea: Role of inflammatory and immune mediated mechanisms. World J Clin Cases 2024; 12:6754-6759. [PMID: 39687652 PMCID: PMC11525906 DOI: 10.12998/wjcc.v12.i35.6754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 08/19/2024] [Accepted: 09/09/2024] [Indexed: 10/24/2024] Open
Abstract
Obstructive sleep apnea (OSA) is often a lifestyle disease associated with obesity, which is rapidly evolving as a major health concern with diverse multisystemic implications. To prevent and mitigate its adverse effects and reduce its burden on society, its aetiopathogeneses must be precisely understood. Numerous studies focusing on the range of diverse anatomic, functional, and lifestyle factors have already been carried out to determine the possible contributory roles of these factors in OSA. Recently, evidence to validate the role of inflammatory pathways and immune mechanisms in the aetiopathogeneses of OSA is being developed. This allows for further research and translation of such knowledge for targeted therapeutic and preventive interventions in patients with or who are at risk of developing OSA.
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Affiliation(s)
- Deb Sanjay Nag
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, Jharkhand, India
| | - Koshy Varghese
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, Jharkhand, India
| | - Amlan Swain
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, Jharkhand, India
- Department of Anaesthesiology, Manipal Tata Medical College, Jamshedpur 831017, India
| | - Roushan Patel
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, Jharkhand, India
- Department of Anaesthesiology, Manipal Tata Medical College, Jamshedpur 831017, India
| | - Seelora Sahu
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, Jharkhand, India
- Department of Anaesthesiology, Manipal Tata Medical College, Jamshedpur 831017, India
| | - Merina Sam
- Department of Anaesthesiology, Tata Main Hospital, Jamshedpur 831001, Jharkhand, India
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Sipowicz K, Pietras T, Sobstyl M, Mosiołek A, Różycka-Kosmalska M, Mosiołek J, Stefanik-Markowska E, Ring M, Kamecki K, Kosmalski M. Sense of loneliness and meaning in life in chronic obstructive pulmonary disease patients. Preliminary studies. Multidiscip Respir Med 2024; 19:994. [PMID: 39530889 PMCID: PMC11614002 DOI: 10.5826/mrm.2024.994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 09/16/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD) interferes with everyday functioning but its impact on the loneliness and the meaning in life of the patients is unclear. OBJECTIVES to determine whether the COPD severity levels correlate with the sense of loneliness and dimensions of the sense of meaning in life. METHODS 144 patients with COPD during a period of absence of an infectious exacerbation were examined. The number of infectious exacerbations over the past year, the Modified Medical Research Council (mMRC) dyspnea score, the COPD Assessment Test (CAT) score were determined as well as the feelings of loneliness using the De Jong Gierveld Loneliness Scale (DJGLS) and the sense of meaning in life using the Life Attitude Profile-Revised (LAP-R) questionnaire. RESULTS The age, the mMRC and CAT scores, the number of pack/years, as well as the number of infectious exacerbations during the year correlated positively with the feeling of loneliness. These variables (except for age) correlated negatively with the LAP-R scales apart from Existential Vacuum, which correlated positively. The subjects from the COPD severity group D (the most seriously ill people) had the highest level of loneliness, while it was the lowest in the subjects from group A (the least ill people). No statistical difference was observed between groups B and C. CONCLUSIONS With the increase in the values of the selected parameters determining the severity of COPD the sense of meaning in life decreases and loneliness intensifies.
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Affiliation(s)
- Kasper Sipowicz
- Department of Interdisciplinary Research in the area of Social Inclusion, The Maria Grzegorzewska University in Warsaw, Warsaw, Poland
| | - Tadeusz Pietras
- The Second Department of Psychiatry, Institute of Psychiatry and Neurology in Warsaw, Warsaw, Poland
- Department of Clinical Pharmacology, Medical University of Lodz, Lodz, Poland
| | - Michał Sobstyl
- Neurosurgery Department, Institute of Psychiatry and Neurology in Warsaw, Warsaw, Poland
| | - Anna Mosiołek
- Department of Forensic Psychiatry, Institute of Psychiatry and Neurology in Warsaw, Warsaw, Poland
| | | | - Jadwiga Mosiołek
- Department of Psychiatry, Medical University of Warsaw, Warsaw, Poland
| | - Ewa Stefanik-Markowska
- The Second Department of Psychiatry, Institute of Psychiatry and Neurology in Warsaw, Warsaw, Poland
| | - Michał Ring
- The Second Department of Psychiatry, Institute of Psychiatry and Neurology in Warsaw, Warsaw, Poland
| | - Krystian Kamecki
- The Second Department of Psychiatry, Institute of Psychiatry and Neurology in Warsaw, Warsaw, Poland
| | - Marcin Kosmalski
- Department of Clinical Pharmacology, Medical University of Lodz, Lodz, Poland
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Nemet M, Vukoja M. Obstructive Sleep Apnea and Acute Lower Respiratory Tract Infections: A Narrative Literature Review. Antibiotics (Basel) 2024; 13:532. [PMID: 38927198 PMCID: PMC11200551 DOI: 10.3390/antibiotics13060532] [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: 05/04/2024] [Revised: 05/27/2024] [Accepted: 06/05/2024] [Indexed: 06/28/2024] Open
Abstract
Both obstructive sleep apnea (OSA) and acute lower respiratory tract infections (LRTIs) are important global health issues. The pathophysiological links between OSA and LRTIs include altered immune responses due to chronic intermittent hypoxia and sleep fragmentation, increased aspiration risk, and a high burden of comorbidities. In this narrative review, we evaluated the current evidence on the association between OSA and the incidence and outcomes of acute LRTIs in adults, specifically community-acquired pneumonia and viral pneumonia caused by influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Studies have demonstrated that OSA patients are more likely to develop bacterial pneumonia and exhibit a higher risk of invasive pneumococcal disease. The risk intensifies with the severity of OSA, influencing hospitalization rates and the need for intensive care. OSA is also associated with an increased risk of contracting influenza and suffering more severe disease, potentially necessitating hospitalization. Similarly, OSA contributes to increased COVID-19 disease severity, reflected by higher rates of hospitalization, longer hospital stays, and a higher incidence of acute respiratory failure. The effect of OSA on mortality rates from these infections is, however, somewhat ambiguous. Finally, we explored antibiotic therapy for OSA patients with LRTIs, addressing care settings, empirical regimens, risks, and pharmacokinetic considerations. Given the substantial burden of OSA and its significant interplay with acute LRTIs, enhanced screening, targeted vaccinations, and optimized management strategies for OSA patients should be prioritized.
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Affiliation(s)
- Marko Nemet
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia;
| | - Marija Vukoja
- Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia;
- The Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, 21204 Novi Sad, Serbia
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Epstein S, Jun D, Deng JC, Zeidler M. Effects of Obstructive Sleep Apnea on Airway Immunity and Susceptibility to Respiratory Infections. Sleep Med Clin 2024; 19:219-228. [PMID: 38692747 DOI: 10.1016/j.jsmc.2024.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/03/2024]
Abstract
Obstructive sleep apnea is a prevalent sleep disorder characterized by recurrent episodes of partial or complete upper airway collapse during sleep, leading to disrupted breathing patterns and intermittent hypoxia. OSA results in systemic inflammation but also directly affects the upper and lower airways leading to upregulation of inflammatory pathways and alterations of the local microbiome. These changes result in increased susceptibility to respiratory infections such as influenza, COVID-19, and bacterial pneumonia. This relationship is more complex and bidirectional in individuals with chronic lung disease such as chronic obstructive lung disease, interstitial lung disease and bronchiectasis.
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Affiliation(s)
- Samuel Epstein
- Division of Pulmonary, Critical Care and Sleep Medicine, David Geffen School of Medicine, UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095, USA; Division of Pulmonary, Critical Care and Sleep Medicine, Greater Los Angeles VA Healthcare System, 11301 Wilshire Boulevard 111Q, Los Angeles, CA 90073, USA
| | - Dale Jun
- Division of Pulmonary, Critical Care and Sleep Medicine, David Geffen School of Medicine, UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095, USA; Division of Pulmonary, Critical Care and Sleep Medicine, Greater Los Angeles VA Healthcare System, 11301 Wilshire Boulevard 111Q, Los Angeles, CA 90073, USA
| | - Jane C Deng
- Pulmonary Medicine, VA Ann Arbor Healthcare System, 2215 Fuller Road, Ann Arbor, MI 48105, USA; Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA
| | - Michelle Zeidler
- Division of Pulmonary, Critical Care and Sleep Medicine, David Geffen School of Medicine, UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095, USA; Division of Pulmonary, Critical Care and Sleep Medicine, Greater Los Angeles VA Healthcare System, 11301 Wilshire Boulevard 111Q, Los Angeles, CA 90073, USA.
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Wang Y, Wang D, Hao H, Cui J, Huang L, Liang Q. The association between cadmium exposure and the risk of chronic obstructive pulmonary disease: A systematic review and meta-analysis. JOURNAL OF HAZARDOUS MATERIALS 2024; 469:133828. [PMID: 38412643 DOI: 10.1016/j.jhazmat.2024.133828] [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: 12/06/2023] [Revised: 01/28/2024] [Accepted: 02/16/2024] [Indexed: 02/29/2024]
Abstract
According to the World Health Organization, chronic obstructive pulmonary disease (COPD) was one of the top ten causes of death worldwide in 2019. The ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) provides a useful indicator for the diagnosis of COPD. Existing data have demonstrated that cadmium (Cd) exposure is associated with COPD. However, data concerning the incidence and progression of cadmium-induced COPD is inconsistent. To explore the relationship between cadmium exposure and the risk of COPD in humans, through January 12, 2023, we conducted a thorough search of the PubMed, Cochrane, Web of Science, Embase and Scopus databases for relevant material. In this study, a meta-analysis was conducted to evaluate the association between cadmium and COPD. This meta-analysis indicated that exposure to cadmium (per 1 μg/L increase) was associated with reduced FEV1/FVC (% change = -47.54%, 95% CI: -54.99% to -40.09%). Subgroup analysis showed that the combined effect estimates were significantly higher in the COPD patient group (% change = -54.66%, 95% CI: -83.32% to -26.00%) than in the general population (% change = -52.11%, 95%CI: -60.53% to -43.70%). Therefore, we conclude that cadmium exposure is associated with reduced FEV1/FVC, which suggests a risk for COPD.
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Affiliation(s)
- Yali Wang
- School of Public Health, Baotou Medical College, Baotou 014030, Inner Mongolia, China
| | - Donglei Wang
- School of Public Health, Baotou Medical College, Baotou 014030, Inner Mongolia, China
| | - Hongyu Hao
- School of Public Health, Baotou Medical College, Baotou 014030, Inner Mongolia, China
| | - Jinjin Cui
- School of Public Health, Baotou Medical College, Baotou 014030, Inner Mongolia, China
| | - Lihua Huang
- School of Public Health, Baotou Medical College, Baotou 014030, Inner Mongolia, China.
| | - Qingqing Liang
- School of Public Health, Baotou Medical College, Baotou 014030, Inner Mongolia, China.
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Lei X, Lu T. Single-cell sequencing reveals lung cell fate evolution initiated by smoking to explore gene predictions of correlative diseases. Toxicol Mech Methods 2024; 34:369-384. [PMID: 38064719 DOI: 10.1080/15376516.2023.2293117] [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: 10/04/2023] [Accepted: 12/02/2023] [Indexed: 01/11/2024]
Abstract
Continuous smoking leads to adaptive regulation and physiological changes in lung tissue and cells, and is an inductive factor for many diseases, making smokers face the risk of malignant and nonmalignant diseases. The impact of research in this area is getting more and more in-depth, but the stimulant effect, mechanism of action and response mechanism of the main cells in the lungs caused by smoke components have not yet been fully elucidated, and the early diagnosis and identification of various diseases induced by smoke toxins have not yet formed a systematic relationship method. In this study, single-cell transcriptome data were generated from three lung samples of smokers and nonsmokers through scRNA-seq technology, revealing the influence of smoking on lung tissue and cells and the changes in immune response. The results show that: through UMAP cell clustering, 16 intermediate cell states of 23 cell clusters of the four main cell types in the lung are revealed, the differences of the main cell groups between smokers and nonsmokers are explained, and the human lung cells are clarified. Components and their marker genes, screen for new marker genes that can be used in the evolution of intermediate-state cells, and at the same time, the analysis of lung cell subgroups reveals the changes in the intermediate state of cells under smoke stimulation, forming a subtype intermediate state cell map. Pseudo-time ordering analysis, to determine the pattern of dynamic processes experienced by cells, differential expression analysis of different branch cells, to clarify the expression rules of cells at different positions, to clarify the evolution process of the intermediate state of cells, and to clarify the response of lung tissue and cells to smoke components mechanism. The development of this study provides new diagnosis and treatment ideas for early disease detection, identification, disease prevention and treatment of patients with smoking-related diseases, and lays a theoretical foundation based on cell and molecular regulation.
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Affiliation(s)
- Xu Lei
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Taiying Lu
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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Shen H, Ma Y, Qiao Y, Zhang C, Chen J, Zhang R. Application of Deferoxamine in Tissue Regeneration Attributed to Promoted Angiogenesis. Molecules 2024; 29:2050. [PMID: 38731540 PMCID: PMC11085206 DOI: 10.3390/molecules29092050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 04/19/2024] [Accepted: 04/25/2024] [Indexed: 05/13/2024] Open
Abstract
Deferoxamine, an iron chelator used to treat diseases caused by excess iron, has had a Food and Drug Administration-approved status for many years. A large number of studies have confirmed that deferoxamine can reduce inflammatory response and promote angiogenesis. Blood vessels play a crucial role in sustaining vital life by facilitating the delivery of immune cells, oxygen, and nutrients, as well as eliminating waste products generated during cellular metabolism. Dysfunction in blood vessels may contribute significantly to the development of life-threatening diseases. Anti-angiogenesis therapy and pro-angiogenesis/angiogenesis strategies have been frequently recommended for various diseases. Herein, we describe the mechanism by which deferoxamine promotes angiogenesis and summarize its application in chronic wounds, bone repair, and diseases of the respiratory system. Furthermore, we discuss the drug delivery system of deferoxamine for treating various diseases, providing constructive ideas and inspiration for the development of new treatment strategies.
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Affiliation(s)
- Haijun Shen
- Department of Preventive Medicine and Public Health Laboratory Science, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, China; (Y.M.); (Y.Q.); (C.Z.); (J.C.)
| | - Yane Ma
- Department of Preventive Medicine and Public Health Laboratory Science, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, China; (Y.M.); (Y.Q.); (C.Z.); (J.C.)
| | - Yi Qiao
- Department of Preventive Medicine and Public Health Laboratory Science, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, China; (Y.M.); (Y.Q.); (C.Z.); (J.C.)
| | - Chun Zhang
- Department of Preventive Medicine and Public Health Laboratory Science, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, China; (Y.M.); (Y.Q.); (C.Z.); (J.C.)
| | - Jialing Chen
- Department of Preventive Medicine and Public Health Laboratory Science, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, China; (Y.M.); (Y.Q.); (C.Z.); (J.C.)
| | - Ran Zhang
- Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, No. 42 Baiziting, Nanjing 210009, China
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Tan L, Yang X, Zhang J, Zhou K. Correlation Between HIF1-A Expression and Airway Remodeling in COPD. Int J Chron Obstruct Pulmon Dis 2024; 19:921-931. [PMID: 38633565 PMCID: PMC11022883 DOI: 10.2147/copd.s447256] [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: 11/12/2023] [Accepted: 04/07/2024] [Indexed: 04/19/2024] Open
Abstract
Background Airway remodeling is a significant pathological characteristic of chronic obstructive pulmonary disease (COPD). In recent years, hypoxia-inducible factor 1-α (HIF-1α), a member of the hypoxia-inducible factor protein family, has gained attention. However, the potential correlation between HIF-1α and COPD airway remodeling remains unclear. Objective This study explored the expression patterns of HIF-1α in patients with COPD and its association with airway remodelling. This investigation aims to furnish novel insights for the clinical identification of prospective therapeutic targets for ameliorating COPD-related airway remodelling. Patients and Methods A total of 88 subjects were included, consisting of 28 controls and 60 COPD patients. Various staining methods were employed to observe the pathological changes in airway tissues. Immunohistochemistry was utilized to detect the expression of HIF-1α and MMP9 (matrix metalloproteinase 9) in airway tissues. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration in serum of HIF-1α and MMP9. Computed tomography (CT) airway parameters were measured in all participants to assess airway remodeling. The relationship between serum HIF-1α and MMP9 concentrations and airway parameters was analyzed. Results Staining of airway structures in COPD patients revealed significant pathological changes associated with airway remodelling, including mixed cilia and subepithelial fibrosis. The expression of HIF-1α and MMP9 was significantly higher in both human airway tissue and serum compared to controls. Chest CT scans exhibited typical imaging features of airway remodeling and increased airway parameters. Conclusion The findings suggest a correlation between increased HIF-1α expression and COPD airway remodelling. This study provides novel evidence that HIF-1α may be a potential biomarker for airway remodelling in COPD patients.
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Affiliation(s)
- Lingfang Tan
- The Nanhua Affiliated Hospital, Department of Respiratory Physicians, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China
| | - Xuefeng Yang
- The Nanhua Affiliated Hospital, Department of General Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China
| | - Jianxin Zhang
- The Nanhua Affiliated Hospital, Department of Cardiothoracic Surgeon, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China
| | - Kebing Zhou
- The Nanhua Affiliated Hospital, Department of Respiratory Physicians, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China
- The Nanhua Affiliated Hospital, Department of General Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China
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Deng R, Ma X, Zhang H, Chen J, Liu M, Chen L, Xu H. Role of HIF-1α in hypercoagulable state of COPD in rats. Arch Biochem Biophys 2024; 753:109903. [PMID: 38253248 DOI: 10.1016/j.abb.2024.109903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 01/18/2024] [Accepted: 01/19/2024] [Indexed: 01/24/2024]
Abstract
OBJECTIVE To explore the role of HIF-1α in hypercoagulable state of COPD induced by lipopolysaccharide plus smoking in rats. It also has to explore the regulatory mechanism of HIF-1α-EPO/EDN-1/VEGF pathway by using its activator and inhibitor. METHODS 60 Sprague-Dawley rats (SD rats) were randomly divided into healthy control group, COPD hypercoagulable control group, activator group, and inhibitor group with 15 rats in each group. The healthy control group was fed freely. The other groups were given smoke and lipopolysaccharide by tracheal instillation to establish the experimental animal model of COPD hypercoagulability. After successful modeling, each experimental group was given 0.9 % sodium chloride solution and corresponding drugs by intraperitoneal injection for 7 days. Lung function was detected after drug administration. Hematoxylin-eosin staining was used to observe the pathological changes of lung tissue. Enzyme-linked immunosorbent assay was used to detect serum D-D,F (1 + 2),IL-6,TNF-α. The mRNA expressions of HIF-1α, EPO, EDN-1, and VEGF were detected by RT-PCR. Western-Blot and IHC were used to detect the expression of HIF-1α, EPO, EDN-1, and VEGF in lung tissue of rats. RESULTS Compared with the healthy control group, rats in COPD hypercoagulable control group had COPD symptoms/signs, decreased lung function, increased the expression of serum D-D and F (1 + 2), increased the expression of inflammatory factors IL-6,TNF-α, and increased the expression of proteins HIF-1α, EPO, EDN-1 and VEGF. Compared with COPD hypercoagulable control group, lung function in activator group and inhibitor group had no obvious changes. The expressions of serum D-D,F (1 + 2),IL-6,TNF-α in activator group have increased noticeably. The expressions of proteins HIF-1α, EPO, EDN-1, and VEGF have further increased. Compared with COPD hypercoagulable control group, the expression of serum D-D, F (1 + 2), HIF-1α, EPO, EDN-1, and VEGF in the inhibitor group decreased. CONCLUSION HIF-1α-EPO/EDN-1/VEGF pathway plays an important role in the hypercoagulable state of COPD. HIF-1α inhibitor can improve airway inflammation and reduce hypercoagulability in COPD model rats.
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Affiliation(s)
- Ruicheng Deng
- The Second Clinical Medicine School of Ningxia Medical University (The First People's Hospital of Yinchuan), 750001, Yinchuan, Ningxia, China
| | - Xiaoyong Ma
- Department of Traditional Chinese Medicine, General Hospital of Ningxia Medical University, 750001, Yinchuan, Ningxia, China
| | - Huifang Zhang
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Ningxia Medical University (The First People's Hospital of Yinchuan), 750001, Yinchuan, Ningxia, China
| | - Juanxia Chen
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Ningxia Medical University (The First People's Hospital of Yinchuan), 750001, Yinchuan, Ningxia, China
| | - Meifang Liu
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Ningxia Medical University (The First People's Hospital of Yinchuan), 750001, Yinchuan, Ningxia, China
| | - Lijun Chen
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Ningxia Medical University (The First People's Hospital of Yinchuan), 750001, Yinchuan, Ningxia, China.
| | - Haiyang Xu
- Department of Hematology, The Second Affiliated Hospital of Ningxia Medical University (The First People's Hospital of Yinchuan), 750001, Yinchuan, Ningxia, China
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12
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Liu L, Fan H, Li L, Fan Y. Acarbose reduces Pseudomonas aeruginosa respiratory tract infection in type 2 diabetic mice. Respir Res 2023; 24:312. [PMID: 38098038 PMCID: PMC10722695 DOI: 10.1186/s12931-023-02619-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Accepted: 11/28/2023] [Indexed: 12/17/2023] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is widely prevalent worldwide, and respiratory tract infections (RTIs) have become the primary cause of death for T2DM patients who develop concurrent infections. Among these, Pseudomonas aeruginosa infection has been found to exhibit a high mortality rate and poor prognosis and is frequently observed in bacterial infections that are concurrent with COVID-19. Studies have suggested that acarbose can be used to treat T2DM and reduce inflammation. Our objective was to explore the effect of acarbose on P. aeruginosa RTI in T2DM individuals and elucidate its underlying mechanism. METHODS High-fat diet (HFD) induction and P. aeruginosa inhalation were used to establish a RTI model in T2DM mice. The effect and mechanism of acarbose administered by gavage on P. aeruginosa RTI were investigated in T2DM and nondiabetic mice using survival curves, pathological examination, and transcriptomics. RESULTS We found that P. aeruginosa RTI was more severe in T2DM mice than in nondiabetic individuals, which could be attributed to the activation of the NF-κB and TREM-1 signaling pathways. When acarbose alleviated P. aeruginosa RTI in T2DM mice, both HIF-1α and NF-κB signaling pathways were inhibited. Furthermore, inhibition of the calcium ion signaling pathway and NF-κB signaling pathway contributed to the attenuation of P. aeruginosa RTI by acarbose in nondiabetic mice. CONCLUSIONS This study confirmed the attenuating effect of acarbose on P. aeruginosa RTIs in T2DM and nondiabetic mice and investigated its mechanism, providing novel support for its clinical application in related diseases.
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Affiliation(s)
- Lin Liu
- Department of Otolaryngology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, People's Republic of China
- Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, People's Republic of China
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Haiyang Fan
- Department of Otolaryngology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, People's Republic of China
- Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, People's Republic of China
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Liang Li
- Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, People's Republic of China.
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
| | - Yunping Fan
- Department of Otolaryngology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, People's Republic of China.
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13
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Cao Y, Pan H, Yang Y, Zhou J, Zhang G. Screening of potential key ferroptosis-related genes in Chronic Obstructive Pulmonary Disease. Int J Chron Obstruct Pulmon Dis 2023; 18:2849-2860. [PMID: 38059012 PMCID: PMC10697092 DOI: 10.2147/copd.s422835] [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: 06/29/2023] [Accepted: 11/11/2023] [Indexed: 12/08/2023] Open
Abstract
PURPOSE Ferroptosis plays essential roles in the development of COPD. We aim to identify the potential ferroptosis-related genes of COPD through bioinformatics analysis. METHODS The RNA expression profile dataset GSE148004 was obtained from the GEO database. The ferroptosis-related genes were obtained from the FerrDb database. The potential differentially expressed ferroptosis-related genes of COPD were screened by R software. Then, protein-protein interactions (PPI), correlation analysis, gene-ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied for the differentially expressed ferroptosis-related genes. Finally, hub gene-microRNA(miRNA), hug gene-transcription factor interaction networks were constructed by miRTarBase v8.0 and JASPAR respectively, and hub gene drugs were predicted by the Enrichr database. RESULTS A total of 41 differentially expressed ferroptosis-related genes (22 up-regulated genes and 19 down-regulated genes) were identified between 7 COPD patients and 9 healthy controls. The PPI results demonstrated that these ferroptosis-related genes interacted with each other. The GO and KEGG enrichment analyses of differentially expressed ferroptosis-related genes indicated several enriched terms related to ferroptosis, central carbon metabolism in cancer, and the HIF-1 signaling pathway. The crucial miRNAs and drugs associated with the top genes were identified. CONCLUSION We identified 41 potential ferroptosis-related genes in COPD through bioinformatics analysis. HIF1A, PPARG, and KRAS may affect the development of COPD by regulating ferroptosis. These results may expand our understanding of COPD and might be useful in the treatment of COPD.
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Affiliation(s)
- Yumeng Cao
- Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China
| | - Huaqin Pan
- Transplantation Intensive Care Unit, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei, 430071, People’s Republic of China
| | - Yanwei Yang
- Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China
| | - Jingrun Zhou
- Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China
| | - Guqin Zhang
- Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China
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14
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Li S, Huang Q, Nan W, He B. Association between serum phosphate and in-hospital mortality of patients with AECOPD: A retrospective analysis on eICU database. Heliyon 2023; 9:e19748. [PMID: 37809538 PMCID: PMC10559067 DOI: 10.1016/j.heliyon.2023.e19748] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 08/02/2023] [Accepted: 08/31/2023] [Indexed: 10/10/2023] Open
Abstract
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an important adverse event in the development of chronic obstructive pulmonary disease (COPD). Hyperphosphatemia is associated with higher mortality in patients with multiple diseases. In this study, we aimed to determine the relationship between serum phosphate and the risk of in-hospital mortality in patients with AECOPD. Methods: In the present study, patients with AECOPD were enrolled in the electronic Intensive Care Unit Collaborative Research Database (eICU-CRD), and divided into three groups according to the tertiles of serum phosphate level. The primary outcome measure was all-cause in-hospital mortality. The association between serum phosphate level and in-hospital mortality was investigated using multivariate logistic regression analysis. Moreover, subgroup analysis was performed to explore whether the relationship was consistent among different subgroups. Results: A total of 1199 AECOPD patients were included in this study. Non-survivors had higher serum phosphate levels than survivors. All patients were classified into lowest tertile, median tertile, and highest tertile, respectively. Multivariate logistic regression analysis indicated that serum phosphate was positively associated with in-hospital mortality after adjusting for confounders. Moreover, there was a significant trend across tertiles when serum phosphate level was diverted as a categorical variable. In addition, subgroup analysis demonstrated that serum phosphate was consistently associated with a higher risk of in-hospital mortality in different subgroups. Conclusion: Higher serum phosphate was positively associated with the increased in-hospital mortality in patients with AECOPD. Hyperphosphatemia may be an underlying high-risk factor for in-hospital mortality owing to AECOPD.
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Affiliation(s)
- Siqi Li
- Department of Geriatric Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Qiong Huang
- Department of Geriatric Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Wenbin Nan
- Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha 410011, China
| | - Baimei He
- Department of Geriatric Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
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Jin M, He B, Cai X, Lei Z, Sun T. Research progress of nanoparticle targeting delivery systems in bacterial infections. Colloids Surf B Biointerfaces 2023; 229:113444. [PMID: 37453264 DOI: 10.1016/j.colsurfb.2023.113444] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 06/28/2023] [Accepted: 07/05/2023] [Indexed: 07/18/2023]
Abstract
Bacterial infection is a huge threat to the health of human beings and animals. The abuse of antibiotics have led to the occurrence of bacterial multidrug resistance, which have become a difficult problem in the treatment of clinical infections. Given the outstanding advantages of nanodrug delivery systems in cancer treatment, many scholars have begun to pay attention to their application in bacterial infections. However, due to the similarity of the microenvironment between bacterial infection lesions and cancer sites, the targeting and accuracy of traditional microenvironment-responsive nanocarriers are questionable. Therefore, finding new specific targets has become a new development direction of nanocarriers in bacterial prevention and treatment. This article reviews the infectious microenvironment induced by bacteria and a series of virulence factors of common pathogenic bacteria and their physiological functions, which may be used as potential targets to improve the targeting accuracy of nanocarriers in lesions.
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Affiliation(s)
- Ming Jin
- School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China; Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China
| | - Bin He
- Institute of Animal Husbandry and Veterinary, Wuhan Academy of Agricultural Sciences, China
| | - Xiaoli Cai
- School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China; Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China
| | - Zhixin Lei
- School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China; Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China.
| | - Taolei Sun
- School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China; Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China.
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Lutsey PL, Zineldin I, Misialek JR, Full KM, Lakshminarayan K, Ishigami J, Cowan LT, Matsushita K, Demmer RT. OSA and Subsequent Risk of Hospitalization With Pneumonia, Respiratory Infection, and Total Infection: The Atherosclerosis Risk in Communities Study. Chest 2023; 163:942-952. [PMID: 36442663 PMCID: PMC10268811 DOI: 10.1016/j.chest.2022.11.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Revised: 10/07/2022] [Accepted: 11/22/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND OSA has been linked to microaspiration, systemic inflammation, and suboptimal immune function. RESEARCH QUESTION Is OSA prospectively associated with risk of hospitalization for pneumonia, respiratory, and total infections? STUDY DESIGN AND METHODS Prospective cohort. Participants in the Atherosclerosis Risk in Communities (ARIC) study (N = 1,586) underwent polysomnography in 1996-1998 and were followed up through 2018 for infection-related hospitalizations. The apnea-hypopnea index (AHI; events/h) was used to categorize participants as having severe OSA (≥ 30), moderate OSA (15-29), mild OSA (5-14), or a normal breathing pattern (< 5). Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. RESULTS ARIC participants were on average 62.7 (SD = 5.5) years of age, and 52.8% were female. Severe OSA was present in 6.0%, moderate OSA in 12.7%, mild OSA in 30.0%, and normal breathing in 51.3%. A total of 253 hospitalizations with pneumonia occurred over a median 20.4 (max, 22.9) years' follow-up. Participants with severe OSA were at 1.87 times (95% CI, 1.19-2.95) higher risk of hospitalization with pneumonia compared with those with a normal breathing pattern after adjustment for demographics and lifestyle behaviors. Results were attenuated modestly after adjustment for BMI (1.62 [0.99-2.63]), and prevalent asthma and COPD (1.62 [0.99-2.63]). A similar pattern existed for hospitalization with respiratory infection and composite infection (demographic and behavior-adjusted HRs: 1.47 [0.96-2.25] and 1.48 [1.07-2.04], respectively). INTERPRETATION Severe OSA was associated with increased risk of hospitalizations with pneumonia in this community-based cohort. OSA patients may benefit from more aggressive efforts to prevent pneumonia and other infectious conditions.
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Affiliation(s)
- Pamela L Lutsey
- Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN.
| | - Islam Zineldin
- M Health Fairview, University of Minnesota, Minneapolis, MN
| | - Jeffrey R Misialek
- Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN
| | - Kelsie M Full
- Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN; Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN
| | - Kamakshi Lakshminarayan
- Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN
| | - Junichi Ishigami
- Division of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Logan T Cowan
- Department of Biostatistics, Epidemiology, and Environmental Health Sciences, Georgia Southern University, Statesboro, GA
| | - Kunihiro Matsushita
- Division of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Ryan T Demmer
- Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN
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Li B, Feng Q, Yu C, Yang J, Qin X, Li X, Cao J, Xu X, Yang C, Jin Y. Predictive value of serum HIF-1α and VEGF for arrhythmia in acute coronary syndrome patients. Exp Biol Med (Maywood) 2023; 248:685-690. [PMID: 37350444 PMCID: PMC10291207 DOI: 10.1177/15353702231171902] [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: 12/28/2022] [Accepted: 02/22/2023] [Indexed: 06/24/2023] Open
Abstract
Percutaneous coronary intervention (PCI) has been widely used in the alleviation of myocardial ischemia in patients with acute coronary syndrome (ACS). However, the incidence of reperfusion arrhythmia (RA) after PCI is high, which seriously affects the prognosis of ACS patients. Therefore, this study aimed to study the predictive value of serum HIF-1α and VEGF levels before PCI for RA in ACS patients post PCI. A total of 200 ACS patients who underwent PCI were selected and divided into those with RA after PCI (RA, n = 93) and those without RA after PCI (non-RA, n = 107) according to Lown grade. Spearman correlation analysis was applied for the relationship between serum hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) levels and Lown grade. Patients with RA after PCI tended to have higher levels of creatine kinase muscle and brain isoenzyme (CK-MB), serum HIF-1α and VEGF before surgery. Low left ventricular ejection fraction (LVEF), high CK-MB, high serum VEGF and HIF-1α were risk factors for RA in ACS patients within 24 h after PCI. Receiver operating characteristic (ROC) analysis revealed that serum HIF-1α and VEGF levels could predict RA in ACS patients after PCI, and the combined detection could increase the sensitivity of single HIF-1α detection and the specificity of single VEGF detection. Lown grade was positively correlated with the serum HIF-1α and VEGF concentrations. In conclusion, serum HIF-1α and VEGF levels before PCI are risk factors for the occurrence of RA in ACS patients after PCI, and have certain predictive values for the occurrence of RA in ACS patients after PCI.
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Affiliation(s)
- Bin Li
- Wuxi No.2 People’s Hospital, The Affiliated Wuxi Clinical College of Nantong University, Wuxi 214002, China
| | - Qiuting Feng
- Department of Cardiology, Jiangnan University Medical Center (JUMC), Wuxi 214002, China
| | - Cheng Yu
- Department of Cardiology, Jiangnan University Medical Center (JUMC), Wuxi 214002, China
| | - Jun Yang
- Department of Cardiology, Jiangnan University Medical Center (JUMC), Wuxi 214002, China
| | - Xian Qin
- Department of Cardiology, Jiangnan University Medical Center (JUMC), Wuxi 214002, China
| | - Xing Li
- Department of Cardiology, Jiangnan University Medical Center (JUMC), Wuxi 214002, China
| | - Jianing Cao
- Department of Cardiology, Jiangnan University Medical Center (JUMC), Wuxi 214002, China
| | - Xin Xu
- Department of Cardiology, Jiangnan University Medical Center (JUMC), Wuxi 214002, China
| | - Chenjian Yang
- Department of Cardiology, Jiangnan University Medical Center (JUMC), Wuxi 214002, China
| | - Yan Jin
- Wuxi No.2 People’s Hospital, The Affiliated Wuxi Clinical College of Nantong University, Wuxi 214002, China
- Department of Cardiology, Jiangnan University Medical Center (JUMC), Wuxi 214002, China
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Sun Z, Lin J, Zhang T, Sun X, Wang T, Duan J, Yao K. Combining bioinformatics and machine learning to identify common mechanisms and biomarkers of chronic obstructive pulmonary disease and atrial fibrillation. Front Cardiovasc Med 2023; 10:1121102. [PMID: 37057099 PMCID: PMC10086368 DOI: 10.3389/fcvm.2023.1121102] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Accepted: 03/14/2023] [Indexed: 03/30/2023] Open
Abstract
BackgroundPatients with chronic obstructive pulmonary disease (COPD) often present with atrial fibrillation (AF), but the common pathophysiological mechanisms between the two are unclear. This study aimed to investigate the common biological mechanisms of COPD and AF and to search for important biomarkers through bioinformatic analysis of public RNA sequencing databases.MethodsFour datasets of COPD and AF were downloaded from the Gene Expression Omnibus (GEO) database. The overlapping genes common to both diseases were screened by WGCNA analysis, followed by protein-protein interaction network construction and functional enrichment analysis to elucidate the common mechanisms of COPD and AF. Machine learning algorithms were also used to identify key biomarkers. Co-expression analysis, “transcription factor (TF)-mRNA-microRNA (miRNA)” regulatory networks and drug prediction were performed for key biomarkers. Finally, immune cell infiltration analysis was performed to evaluate further the immune cell changes in the COPD dataset and the correlation between key biomarkers and immune cells.ResultsA total of 133 overlapping genes for COPD and AF were obtained, and the enrichment was mainly focused on pathways associated with the inflammatory immune response. A key biomarker, cyclin dependent kinase 8 (CDK8), was identified through screening by machine learning algorithms and validated in the validation dataset. Twenty potential drugs capable of targeting CDK8 were obtained. Immune cell infiltration analysis revealed the presence of multiple immune cell dysregulation in COPD. Correlation analysis showed that CDK8 expression was significantly associated with CD8+ T cells, resting dendritic cell, macrophage M2, and monocytes.ConclusionsThis study highlights the role of the inflammatory immune response in COPD combined with AF. The prominent link between CDK8 and the inflammatory immune response and its characteristic of not affecting the basal expression level of nuclear factor kappa B (NF-kB) make it a possible promising therapeutic target for COPD combined with AF.
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Affiliation(s)
- Ziyi Sun
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Jianguo Lin
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, China Academy of Chinese Medical Sciences, Beijing, China
| | - Tianya Zhang
- Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Xiaoning Sun
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, China Academy of Chinese Medical Sciences, Beijing, China
| | - Tianlin Wang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Jinlong Duan
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Kuiwu Yao
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Eye Hospital China Academy of Chinese Medical Sciences, China Academy of Chinese Medical Sciences, Beijing, China
- Correspondence: Kuiwu Yao
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Berggren-Nylund R, Ryde M, Löfdahl A, Ibáñez-Fonseca A, Kåredal M, Westergren-Thorsson G, Tufvesson E, Larsson-Callerfelt AK. Effects of hypoxia on bronchial and alveolar epithelial cells linked to pathogenesis in chronic lung disorders. Front Physiol 2023; 14:1094245. [PMID: 36994416 PMCID: PMC10040785 DOI: 10.3389/fphys.2023.1094245] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 03/02/2023] [Indexed: 03/15/2023] Open
Abstract
Introduction: Chronic lung disorders involve pathological alterations in the lung tissue with hypoxia as a consequence. Hypoxia may influence the release of inflammatory mediators and growth factors including vascular endothelial growth factor (VEGF) and prostaglandin (PG)E2. The aim of this work was to investigate how hypoxia affects human lung epithelial cells in combination with profibrotic stimuli and its correlation to pathogenesis.Methods: Human bronchial (BEAS-2B) and alveolar (hAELVi) epithelial cells were exposed to either hypoxia (1% O2) or normoxia (21% O2) during 24 h, with or without transforming growth factor (TGF)-β1. mRNA expression of genes and proteins related to disease pathology were analysed with qPCR, ELISA or immunocytochemistry. Alterations in cell viability and metabolic activity were determined.Results: In BEAS-2B and hAELVi, hypoxia significantly dowregulated genes related to fibrosis, mitochondrial stress, oxidative stress, apoptosis and inflammation whereas VEGF receptor 2 increased. Hypoxia increased the expression of Tenascin-C, whereas both hypoxia and TGF-β1 stimuli increased the release of VEGF, IL-6, IL-8 and MCP-1 in BEAS-2B. In hAELVi, hypoxia reduced the release of fibroblast growth factor, epidermal growth factor, PGE2, IL-6 and IL-8, whereas TGF-β1 stimulus significantly increased the release of PGE2 and IL-6. TGF-β1 stimulated BEAS-2B cells showed a decreased release of VEGF-A and IL-8, while TGF-β1 stimulated hAELVi cells showed a decreased release of PGE2 and IL-8 during hypoxia compared to normoxia. Metabolic activity was significantly increased by hypoxia in both epithelial cell types.Discussion: In conclusion, our data indicate that bronchial and alveolar epithelial cells respond differently to hypoxia and profibrotic stimuli. The bronchial epithelium appears more responsive to changes in oxygen levels and remodelling processes compared to the alveoli, suggesting that hypoxia may be a driver of pathogenesis in chronic lung disorders.
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Affiliation(s)
| | - Martin Ryde
- Respiratory Medicine, Allergology and Palliative Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
| | - Anna Löfdahl
- Lung Biology, Department of Experimental Medical Science, Lund University, Lund, Sweden
| | - Arturo Ibáñez-Fonseca
- Lung Biology, Department of Experimental Medical Science, Lund University, Lund, Sweden
| | - Monica Kåredal
- Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden
| | | | - Ellen Tufvesson
- Respiratory Medicine, Allergology and Palliative Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden
| | - Anna-Karin Larsson-Callerfelt
- Lung Biology, Department of Experimental Medical Science, Lund University, Lund, Sweden
- *Correspondence: Anna-Karin Larsson-Callerfelt,
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Faverio P, Zanini U, Monzani A, Parati G, Luppi F, Lombardi C, Perger E. Sleep-Disordered Breathing and Chronic Respiratory Infections: A Narrative Review in Adult and Pediatric Population. Int J Mol Sci 2023; 24:ijms24065504. [PMID: 36982578 PMCID: PMC10052011 DOI: 10.3390/ijms24065504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 03/07/2023] [Accepted: 03/11/2023] [Indexed: 03/17/2023] Open
Abstract
Sleep-disordered breathing (SDB) comprises different diseases characterized by abnormal respiratory patterns during sleep including obstructive sleep apnea. SDB prevalence and impact in patients with chronic respiratory infections have been only marginally studied. The purpose of this narrative review is to report the prevalence and impact of SDB in chronic respiratory infections, including cystic fibrosis (CF), bronchiectasis and mycobacterial infections, and explore the possible pathophysiological mechanisms. Common pathophysiological mechanisms, underlying SDB onset in all chronic respiratory infections, include inflammation, which plays a central role, chronic nocturnal cough and pain, excessive production of mucous plugs, presence of obstructive and/or restrictive ventilatory impairment, upper airways involvement, and comorbidities, such as alteration of nutritional status. SDB may affect about 50% of patients with bronchiectasis. The severity of the disease, e.g., patients colonized with P. aeruginosa and frequent exacerbators, as well as comorbidities, such as chronic obstructive pulmonary disease and primary ciliary dyskinesia, may impact SDB onset. SDB may also frequently complicate the clinical course of both children and adults with CF, impacting the quality of life and disease prognosis, suggesting that their routine assessment should be incorporated into the clinical evaluation of patients from the first stages of the disease regardless of suggestive symptoms, in order to avoid late diagnosis. Finally, although the prevalence of SDB in patients with mycobacterial infections is uncertain, extrapulmonary manifestations, particularly nasopharyngeal locations, and concomitant symptoms, such as body pain and depression, may act as atypical predisposing factors for their development.
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Affiliation(s)
- Paola Faverio
- UOC Pneumologia, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy; (P.F.); (U.Z.)
- School of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy
| | - Umberto Zanini
- UOC Pneumologia, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy; (P.F.); (U.Z.)
- School of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy
| | - Anna Monzani
- UOC Pneumologia, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy; (P.F.); (U.Z.)
| | - Gianfranco Parati
- School of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy
- Istituto Auxologico Italiano, IRCCS, Sleep Disorders Center & Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, 20149 Milan, Italy
| | - Fabrizio Luppi
- UOC Pneumologia, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy; (P.F.); (U.Z.)
- School of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy
| | - Carolina Lombardi
- School of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy
- Istituto Auxologico Italiano, IRCCS, Sleep Disorders Center & Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, 20149 Milan, Italy
| | - Elisa Perger
- Istituto Auxologico Italiano, IRCCS, Sleep Disorders Center & Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, 20149 Milan, Italy
- Correspondence:
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21
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Walters EH, Shukla S, Ward C. Broadening concepts of core pathobiology in various aspects of COPD development. Eur Respir J 2022; 60:2201531. [PMID: 36202414 DOI: 10.1183/13993003.01531-2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 08/23/2022] [Indexed: 11/05/2022]
Affiliation(s)
- Eugene H Walters
- School of Medicine and Menzies Institute, University of Tasmania, Hobart, Australia
| | - Shakti Shukla
- Graduate School of Pharmacy, University of Technology Sydney, Ultimo, Australia
| | - Chis Ward
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University Medical School, Newcastle University, Newcastle Upon Tyne, UK
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22
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Xu YR, Wang AL, Li YQ. Hypoxia-inducible factor 1-alpha is a driving mechanism linking chronic obstructive pulmonary disease to lung cancer. Front Oncol 2022; 12:984525. [PMID: 36338690 PMCID: PMC9634253 DOI: 10.3389/fonc.2022.984525] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Accepted: 10/10/2022] [Indexed: 11/27/2022] Open
Abstract
Patients with chronic obstructive pulmonary disease (COPD), irrespective of their smoking history, are more likely to develop lung cancer than the general population. This is mainly because COPD is characterized by chronic persistent inflammation and hypoxia, which are the risk factors for lung cancer. However, the mechanisms underlying this observation are still unknown. Hypoxia-inducible factor 1-alpha (HIF-1α) plays an important role in the crosstalk that exists between inflammation and hypoxia. Furthermore, HIF-1α is the main regulator of somatic adaptation to hypoxia and is highly expressed in hypoxic environments. In this review, we discuss the molecular aspects of the crosstalk between hypoxia and inflammation, showing that HIF-1α is an important signaling pathway that drives COPD progression to lung cancer. Here, we also provide an overview of HIF-1α and its principal regulatory mechanisms, briefly describe HIF-1α-targeted therapy in lung cancer, and summarize substances that may be used to target HIF-1α at the level of COPD-induced inflammation.
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Affiliation(s)
- Yuan-rui Xu
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
- Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
| | - An-long Wang
- Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
| | - Ya-qing Li
- Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, China
- *Correspondence: Ya-qing Li,
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23
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Wei Y, Giunta S, Xia S. Hypoxia in Aging and Aging-Related Diseases: Mechanism and Therapeutic Strategies. Int J Mol Sci 2022; 23:8165. [PMID: 35897741 PMCID: PMC9330578 DOI: 10.3390/ijms23158165] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 07/12/2022] [Accepted: 07/14/2022] [Indexed: 01/27/2023] Open
Abstract
As the global aging process continues to lengthen, aging-related diseases (e.g., chronic obstructive pulmonary disease (COPD), heart failure) continue to plague the elderly population. Aging is a complex biological process involving multiple tissues and organs and is involved in the development and progression of multiple aging-related diseases. At the same time, some of these aging-related diseases are often accompanied by hypoxia, chronic inflammation, oxidative stress, and the increased secretion of the senescence-associated secretory phenotype (SASP). Hypoxia seems to play an important role in the process of inflammation and aging, but is often neglected in advanced clinical research studies. Therefore, we have attempted to elucidate the role played by different degrees and types of hypoxia in aging and aging-related diseases and their possible pathways, and propose rational treatment options based on such mechanisms for reference.
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Affiliation(s)
- Yaqin Wei
- Department of Geriatrics, Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai 200000, China;
| | - Sergio Giunta
- Casa di Cura Prof. Nobili–GHC Garofalo Health Care, 40035 Bologna, Italy;
| | - Shijin Xia
- Department of Geriatrics, Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai 200000, China;
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24
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Zhou W, Yu T, Hua Y, Hou Y, Ding Y, Nie H. Effects of Hypoxia on Respiratory Diseases: Perspective View of Epithelial Ion Transport. Am J Physiol Lung Cell Mol Physiol 2022; 323:L240-L250. [PMID: 35819839 DOI: 10.1152/ajplung.00065.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The balance of gas exchange and lung ventilation is essential for the maintenance of body homeostasis. There are many ion channels and transporters in respiratory epithelial cells, including epithelial sodium channel, Na,K-ATPase, cystic fibrosis transmembrane conductance regulator, and some transporters. These ion channels/transporters maintain the capacity of liquid layer on the surface of respiratory epithelial cells, and provide an immune barrier for the respiratory system to clear off foreign pathogens. However, in some harmful external environment and/or pathological conditions, the respiratory epithelium is prone to hypoxia, which would destroy the ion transport function of the epithelium and unbalance the homeostasis of internal environment, triggering a series of pathological reactions. Many respiratory diseases associated with hypoxia manifest an increased expression of hypoxia-inducible factor-1, which mediates the integrity of the epithelial barrier and affects epithelial ion transport function. It is important to study the relationship between hypoxia and ion transport function, whereas the mechanism of hypoxia-induced ion transport dysfunction in respiratory diseases is not clear. This review focuses on the relationship of hypoxia and respiratory diseases, as well as dysfunction of ion transport and tight junctions in respiratory epithelial cells under hypoxia.
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Affiliation(s)
- Wei Zhou
- Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang, China
| | - Tong Yu
- Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang, China
| | - Yu Hua
- Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang, China
| | - Yapeng Hou
- Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang, China
| | - Yan Ding
- Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang, China
| | - Hongguang Nie
- Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang, China
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25
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Reig S, Le Gouellec A, Bleves S. What Is New in the Anti–Pseudomonas aeruginosa Clinical Development Pipeline Since the 2017 WHO Alert? Front Cell Infect Microbiol 2022; 12:909731. [PMID: 35880080 PMCID: PMC9308001 DOI: 10.3389/fcimb.2022.909731] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 05/30/2022] [Indexed: 11/16/2022] Open
Abstract
The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Carbapenem-resistant Pseudomonas aeruginosa (CRPA) are considered “critical-priority” bacteria by the World Health Organization (WHO) since 2017 taking into account criteria such as patient mortality, global burden disease, and worldwide trend of multi-drug resistance (MDR). Indeed P. aeruginosa can be particularly difficult to eliminate from patients due to its combinatory antibiotic resistance, multifactorial virulence, and ability to over-adapt in a dynamic way. Research is active, but the course to a validated efficacy of a new treatment is still long and uncertain. What is new in the anti–P. aeruginosa clinical development pipeline since the 2017 WHO alert? This review focuses on new solutions for P. aeruginosa infections that are in active clinical development, i.e., currently being tested in humans and may be approved for patients in the coming years. Among 18 drugs of interest in December 2021 anti–P. aeruginosa development pipeline described here, only one new combination of β-lactam/β-lactamase inhibitor is in phase III trial. Derivatives of existing antibiotics considered as “traditional agents” are over-represented. Diverse “non-traditional agents” including bacteriophages, iron mimetic/chelator, and anti-virulence factors are significantly represented but unfortunately still in early clinical stages. Despite decade of efforts, there is no vaccine currently in clinical development to prevent P. aeruginosa infections. Studying pipeline anti–P. aeruginosa since 2017 up to now shows how to provide a new treatment for patients can be a difficult task. Given the process duration, the clinical pipeline remains unsatisfactory leading best case to the approval of new antibacterial drugs that treat CRPA in several years. Beyond investment needed to build a robust pipeline, the Community needs to reinvent medicine with new strategies of development to avoid the disaster. Among “non-traditional agents”, anti-virulence strategy may have the potential through novel and non-killing modes of action to reduce the selective pressure responsible of MDR.
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Affiliation(s)
- Sébastien Reig
- Laboratoire d’Ingénierie des Systèmes Macromoléculaires (LISM), Institut de Microbiologie, Bioénergies et Biotechnologie (IM2B), Aix-Marseille Université-CNRS, UMR7255, Marseille, France
- *Correspondence: Sébastien Reig, ; Sophie Bleves,
| | - Audrey Le Gouellec
- Laboratoire Techniques de l’Ingénierie Médicale et de la Complexité (UMR5525), Centre National de la Recherche Scientifique, Université Grenoble Alpes, VetAgro Sup, Grenoble INP, CHU Grenoble Alpes, Grenoble, France
| | - Sophie Bleves
- Laboratoire d’Ingénierie des Systèmes Macromoléculaires (LISM), Institut de Microbiologie, Bioénergies et Biotechnologie (IM2B), Aix-Marseille Université-CNRS, UMR7255, Marseille, France
- *Correspondence: Sébastien Reig, ; Sophie Bleves,
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26
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Hypoxia signaling in human health and diseases: implications and prospects for therapeutics. Signal Transduct Target Ther 2022; 7:218. [PMID: 35798726 PMCID: PMC9261907 DOI: 10.1038/s41392-022-01080-1] [Citation(s) in RCA: 183] [Impact Index Per Article: 61.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 06/17/2022] [Accepted: 06/23/2022] [Indexed: 02/07/2023] Open
Abstract
Molecular oxygen (O2) is essential for most biological reactions in mammalian cells. When the intracellular oxygen content decreases, it is called hypoxia. The process of hypoxia is linked to several biological processes, including pathogenic microbe infection, metabolic adaptation, cancer, acute and chronic diseases, and other stress responses. The mechanism underlying cells respond to oxygen changes to mediate subsequent signal response is the central question during hypoxia. Hypoxia-inducible factors (HIFs) sense hypoxia to regulate the expressions of a series of downstream genes expression, which participate in multiple processes including cell metabolism, cell growth/death, cell proliferation, glycolysis, immune response, microbe infection, tumorigenesis, and metastasis. Importantly, hypoxia signaling also interacts with other cellular pathways, such as phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling, nuclear factor kappa-B (NF-κB) pathway, extracellular signal-regulated kinases (ERK) signaling, and endoplasmic reticulum (ER) stress. This paper systematically reviews the mechanisms of hypoxia signaling activation, the control of HIF signaling, and the function of HIF signaling in human health and diseases. In addition, the therapeutic targets involved in HIF signaling to balance health and diseases are summarized and highlighted, which would provide novel strategies for the design and development of therapeutic drugs.
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27
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Zhong S, Yang L, Liu N, Zhou G, Hu Z, Chen C, Wang Y. Identification and validation of aging-related genes in COPD based on bioinformatics analysis. Aging (Albany NY) 2022; 14:4336-4356. [PMID: 35609226 PMCID: PMC9186770 DOI: 10.18632/aging.204064] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 04/12/2022] [Indexed: 11/25/2022]
Abstract
Chronic obstructive pulmonary disease (COPD) is a serious chronic respiratory disorder. One of the major risk factors for COPD progression is aging. Therefore, we investigated aging-related genes in COPD using bioinformatic analyses. Firstly, the Aging Atlas database containing 500 aging-related genes and the Gene Expression Omnibus database (GSE38974) were utilized to screen candidates. A total of 24 candidate genes were identified related to both COPD and aging. Using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we found that this list of 24 genes was enriched in genes associated with cytokine activity, cell apoptosis, NF-κB and IL-17 signaling. Four of these genes (CDKN1A, HIF1A, MXD1 and SOD2) were determined to be significantly upregulated in clinical COPD samples and in cigarette smoke extract-exposed Beas-2B cells in vitro, and their expression was negatively correlated with predicted forced expiratory volume and forced vital capacity. In addition, the combination of expression levels of these four genes had a good discriminative ability for COPD patients (AUC = 0.794, 95% CI 0.743-0.845). All four were identified as target genes of hsa-miR-519d-3p, which was significantly down-regulated in COPD patients. The results from this study proposed that regulatory network of hsa-miR-519d-3p/CDKN1A, HIF1A, MXD1, and SOD2 closely associated with the progression of COPD, which provides a theoretical basis to link aging effectors with COPD progression, and may suggest new diagnostic and therapeutic targets of this disease.
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Affiliation(s)
- Shan Zhong
- Guangdong Key Laboratory of Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518055, P.R. China.,Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen 518061, P.R. China
| | - Li Yang
- Key Laboratory of Interventional Pulmonology of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, P.R. China
| | - Naijia Liu
- Guangdong Key Laboratory of Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518055, P.R. China
| | - Guangkeng Zhou
- Guangdong Key Laboratory of Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518055, P.R. China
| | - Zhangli Hu
- Guangdong Key Laboratory of Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518055, P.R. China.,Longhua Innovation Institute for Biotechnology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, P.R. China
| | - Chengshui Chen
- Key Laboratory of Interventional Pulmonology of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, P.R. China
| | - Yun Wang
- Guangdong Key Laboratory of Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518055, P.R. China
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28
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Locke BW, Lee JJ, Sundar KM. OSA and Chronic Respiratory Disease: Mechanisms and Epidemiology. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19095473. [PMID: 35564882 PMCID: PMC9105014 DOI: 10.3390/ijerph19095473] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 04/22/2022] [Accepted: 04/23/2022] [Indexed: 02/06/2023]
Abstract
Obstructive sleep apnea (OSA) is a highly prevalent disorder that has profound implications on the outcomes of patients with chronic lung disease. The hallmark of OSA is a collapse of the oropharynx resulting in a transient reduction in airflow, large intrathoracic pressure swings, and intermittent hypoxia and hypercapnia. The subsequent cytokine-mediated inflammatory cascade, coupled with tractional lung injury, damages the lungs and may worsen several conditions, including chronic obstructive pulmonary disease, asthma, interstitial lung disease, and pulmonary hypertension. Further complicating this is the sleep fragmentation and deterioration of sleep quality that occurs because of OSA, which can compound the fatigue and physical exhaustion often experienced by patients due to their chronic lung disease. For patients with many pulmonary disorders, the available evidence suggests that the prompt recognition and treatment of sleep-disordered breathing improves their quality of life and may also alter the course of their illness. However, more robust studies are needed to truly understand this relationship and the impacts of confounding comorbidities such as obesity and gastroesophageal reflux disease. Clinicians taking care of patients with chronic pulmonary disease should screen and treat patients for OSA, given the complex bidirectional relationship OSA has with chronic lung disease.
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29
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Ma SL, Hu SY, Li WL, You DL, Jiang TT, Wang L, Wang F, Wu X. Correlation between Traditional Chinese Medicine Syndromes and Type 2 Myocardial Infarction in Critically Ill Patients with Pulmonary Disease. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:9329683. [PMID: 35356241 PMCID: PMC8959955 DOI: 10.1155/2022/9329683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 03/02/2022] [Accepted: 03/03/2022] [Indexed: 11/17/2022]
Abstract
Background Treatment based on syndrome differentiation under the traditional Chinese medicine (TCM) framework has been shown to be helpful in patients with coronary artery disease. We hypothesized that syndrome types could predict the risk of type 2 myocardial infarction (T2MI) caused by imbalance between myocardial oxygen supply and demand in critically ill patients with pulmonary disease. Methods This retrospective study included consecutive critically ill patients with pulmonary disease admitted to the ICU at Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences from January 1, 2017, to July 1, 2019. Diagnosis of T2MI was based on the fourth universal definition of myocardial infarction. Risk factors associated with T2MI were identified using multivariate regression analysis. Results A total of 244 patients were included in the study: 78 who developed T2MI and the remaining 166 who did not develop T2MI during hospitalization. The incidence of phlegm syndrome and deficiency syndrome was 61.9% and 38.1%, respectively. In comparison with the patients with phlegm syndrome, the incidence of T2MI in patients with deficiency syndrome is significantly higher (40.9% vs. 26.5%, P=0.019). In multivariate logistic regression, T2MI was independently associated with the baseline troponin level (OR 12.682, 95% CI 1.397∼115.121; P=0.024), hemoglobin < 55 g/L (OR 12.76, 95% CI 2.359∼69.021; P=0.003), mechanical ventilation (OR 2.244, 95% CI 1.029∼4.892; P=0.042), and TCM deficiency syndrome (OR 2.214, 95% CI 1.032∼4.749; P=0.041). After adjusting for confounding factors in Cox regression models, the hazard ratio (95% confidence interval) of qi deficiency syndrome groups was 1.183 (95% CI 1.053∼3.123, P=0.032). Conclusions Patients with deficiency syndrome are at high risk of T2MI, especially those combined with qi deficiency syndrome.
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Affiliation(s)
- Sheng-Li Ma
- Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Emergency Department, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Shan-You Hu
- Department of Critical Care Medicine, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Wu-Lin Li
- Emergency Department, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Da-Li You
- Department of Critical Care Medicine, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Ting-Ting Jiang
- Department of Critical Care Medicine, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Li Wang
- Emergency Department, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Fei Wang
- Department of Critical Care Medicine, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Xiao Wu
- Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Emergency Department, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China
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30
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Chen H, Yang N, Yang Y, Zheng Y, Xu M, Zhang H, Liu Y, Shen W, Li J. Doxofylline Protects Gram-Negative Pathogens against Antibiotic-Mediated Killing. ACS Infect Dis 2021; 7:3241-3253. [PMID: 34851627 DOI: 10.1021/acsinfecdis.1c00417] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Given the growing rate of Gram-negative bacterial infections, antibiotics are now frequently prescribed for various respiratory diseases. Doxofylline is a newer generation xanthine with both bronchodilating and anti-inflammatory activities, but its influence on antibiotics remains poorly understood. Here, we first report the discovery of doxofylline-induced high minimum inhibitory concentrations of antibiotics. We also showed that doxofylline blocked antimicrobial-mediated killing for Gram-negative pathogens in vitro and in murine lung infection models in vivo. By combining efflux pump inhibition tests, gene expression analyses, and using the gene tolC knockout strain, we found that doxofylline positively regulated gene expression of the AcrAB-TolC efflux pump and attenuated the effect of doxofylline on antibacterial activities in ΔtolC mutants. Notably, doxofylline-mediated protection correlated with decreased reactive oxygen species (ROS) production. Collectively, our study indicates that doxofylline protects Gram-negative bacteria from antimicrobial lethality by regulating the AcrAB-TolC efflux pump in a TolC-dependent manner and suppressing antibiotic-induced ROS accumulation. These results suggest caution when using antibiotics alongside doxofylline in clinical treatment.
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Affiliation(s)
- Haoran Chen
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China
| | - Ning Yang
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China
| | - Yi Yang
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China
| | - Yahong Zheng
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China
| | - Mengran Xu
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China
| | - Hui Zhang
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China
| | - Yanyan Liu
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China
- Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui 230022, China
- Institute of Bacterial Resistance, Anhui Medical University, Hefei, Anhui 230022, China
| | - Weihua Shen
- Department of Special Clinic, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China
| | - Jiabin Li
- Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China
- Department of Molecular Biology, Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui 230022, China
- Anhui Center for Surveillance of Bacterial Resistance, Hefei, Anhui 230022, China
- Institute of Bacterial Resistance, Anhui Medical University, Hefei, Anhui 230022, China
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31
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Kotlyarov S, Bulgakov A. Lipid Metabolism Disorders in the Comorbid Course of Nonalcoholic Fatty Liver Disease and Chronic Obstructive Pulmonary Disease. Cells 2021; 10:2978. [PMID: 34831201 PMCID: PMC8616072 DOI: 10.3390/cells10112978] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 10/25/2021] [Accepted: 10/30/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently among the most common liver diseases. Unfavorable data on the epidemiology of metabolic syndrome and obesity have increased the attention of clinicians and researchers to the problem of NAFLD. The research results allow us to emphasize the systemicity and multifactoriality of the pathogenesis of liver parenchyma lesion. At the same time, many aspects of its classification, etiology, and pathogenesis remain controversial. Local and systemic metabolic disorders are also a part of the pathogenesis of chronic obstructive pulmonary disease and can influence its course. The present article analyzes the metabolic pathways mediating the links of impaired lipid metabolism in NAFLD and chronic obstructive pulmonary disease (COPD). Free fatty acids, cholesterol, and ceramides are involved in key metabolic and inflammatory pathways underlying the pathogenesis of both diseases. Moreover, inflammation and lipid metabolism demonstrate close links in the comorbid course of NAFLD and COPD.
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Affiliation(s)
- Stanislav Kotlyarov
- Department of Nursing, Ryazan State Medical University, 390026 Ryazan, Russia;
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32
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Recent trends of NFκB decoy oligodeoxynucleotide-based nanotherapeutics in lung diseases. J Control Release 2021; 337:629-644. [PMID: 34375688 DOI: 10.1016/j.jconrel.2021.08.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 08/04/2021] [Accepted: 08/05/2021] [Indexed: 02/07/2023]
Abstract
Nuclear factor κB (NFκB) is a unique protein complex that plays a major role in lung inflammation and respiratory dysfunction. The NFκB signaling pathway, therefore becomes an avenue for the development of potential pharmacological interventions, especially in situations where chronic inflammation is often constitutively active and plays a key role in the pathogenesis and progression of the disease. NFκB decoy oligodeoxynucleotides (ODNs) are double-stranded and carry NFκB binding sequences. They prevent the formation of NFκB-mediated inflammatory cytokines and thus have been employed in the treatment of a variety of chronic inflammatory diseases. However, the systemic administration of naked decoy ODNs restricts their therapeutic effectiveness because of their poor pharmacokinetic profile, instability, degradation by cellular enzymes and their low cellular uptake. Both structural modification and nanotechnology have shown promising results in enhancing the pharmacokinetic profiles of potent therapeutic substances and have also shown great potential in the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. In this review, we examine the contribution of NFκB activation in respiratory diseases and recent advancements in the therapeutic use of decoy ODNs. In addition, we also highlight the limitations and challenges in use of decoy ODNs as therapeutic molecules, cellular uptake of decoy ODNs, and the current need for novel delivery systems to provide efficient delivery of decoy ODNs. Furthermore, this review provides a common platform for discussion on the existence of decoy ODNs, as well as outlining perspectives on the latest generation of delivery systems that encapsulate decoy ODNs and target NFκB in respiratory diseases.
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Li X, Cai H, Cai Y, Zhang Q, Ding Y, Zhuang Q. Investigation of a Hypoxia-Immune-Related Microenvironment Gene Signature and Prediction Model for Idiopathic Pulmonary Fibrosis. Front Immunol 2021; 12:629854. [PMID: 34194423 PMCID: PMC8236709 DOI: 10.3389/fimmu.2021.629854] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 05/25/2021] [Indexed: 12/20/2022] Open
Abstract
Background There is growing evidence found that the role of hypoxia and immune status in idiopathic pulmonary fibrosis (IPF). However, there are few studies about the role of hypoxia and immune status in the lung milieu in the prognosis of IPF. This study aimed to develop a hypoxia-immune-related prediction model for the prognosis of IPF. Methods Hypoxia and immune status were estimated with microarray data of a discovery cohort from the GEO database using UMAP and ESTIMATE algorithms respectively. The Cox regression model with the LASSO method was used for identifying prognostic genes and developing hypoxia-immune-related genes. Cibersort was used to evaluate the difference of 22 kinds of immune cell infiltration. Three independent validation cohorts from GEO database were used for external validation. Peripheral blood mononuclear cell (PBMC) and bronchoalveolar lavage fluid (BALF) were collected to be tested by Quantitative reverse transcriptase-PCR (qRT-PCR) and flow cytometry from 22 clinical samples, including 13 healthy controls, six patients with non-fibrotic pneumonia and three patients with pulmonary fibrosis. Results Hypoxia and immune status were significantly associated with the prognosis of IPF patients. High hypoxia and high immune status were identified as risk factors for overall survival. CD8+ T cell, activated CD4+ memory T cell, NK cell, activated mast cell, M1 and M0 macrophages were identified as key immune cells in hypoxia-immune-related microenvironment. A prediction model for IPF prognosis was established based on the hypoxia-immune-related one protective and nine risk DEGs. In the independent validation cohorts, the prognostic prediction model performed the significant applicability in peripheral whole blood, peripheral blood mononuclear cell, and lung tissue of IPF patients. The preliminary clinical specimen validation suggested the reliability of most conclusions. Conclusions The hypoxia-immune-based prediction model for the prognosis of IPF provides a new idea for prognosis and treatment.
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Affiliation(s)
- Xinyu Li
- Transplantation Center, The 3rd Xiangya Hospital, Central South University, Changsha, China.,Xiangya School of Medicine, Central South University, Changsha, China
| | - Haozheng Cai
- Transplantation Center, The 3rd Xiangya Hospital, Central South University, Changsha, China
| | - Yufeng Cai
- School of Life Science, Central South University, Changsha, China
| | - Quyan Zhang
- Transplantation Center, The 3rd Xiangya Hospital, Central South University, Changsha, China.,Xiangya School of Medicine, Central South University, Changsha, China
| | - Yinghe Ding
- Transplantation Center, The 3rd Xiangya Hospital, Central South University, Changsha, China.,Xiangya School of Medicine, Central South University, Changsha, China
| | - Quan Zhuang
- Transplantation Center, The 3rd Xiangya Hospital, Central South University, Changsha, China.,Research Center of National Health Ministry on Transplantation Medicine, Changsha, China
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34
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Alemao CA, Budden KF, Gomez HM, Rehman SF, Marshall JE, Shukla SD, Donovan C, Forster SC, Yang IA, Keely S, Mann ER, El Omar EM, Belz GT, Hansbro PM. Impact of diet and the bacterial microbiome on the mucous barrier and immune disorders. Allergy 2021; 76:714-734. [PMID: 32762040 DOI: 10.1111/all.14548] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 07/10/2020] [Accepted: 07/30/2020] [Indexed: 12/11/2022]
Abstract
The prevalence of chronic immune and metabolic disorders is increasing rapidly. In particular, inflammatory bowel diseases, obesity, diabetes, asthma and chronic obstructive pulmonary disease have become major healthcare and economic burdens worldwide. Recent advances in microbiome research have led to significant discoveries of associative links between alterations in the microbiome and health, as well as these chronic supposedly noncommunicable, immune/metabolic disorders. Importantly, the interplay between diet, microbiome and the mucous barrier in these diseases has gained significant attention. Diet modulates the mucous barrier via alterations in gut microbiota, resulting in either disease onset/exacerbation due to a "poor" diet or protection against disease with a "healthy" diet. In addition, many mucosa-associated disorders possess a specific gut microbiome fingerprint associated with the composition of the mucous barrier, which is further influenced by host-microbiome and inter-microbial interactions, dietary choices, microbe immigration and antimicrobials. Our review focuses on the interactions of diet (macronutrients and micronutrients), gut microbiota and mucous barriers (gastrointestinal and respiratory tract) and their importance in the onset and/or progression of major immune/metabolic disorders. We also highlight the key mechanisms that could be targeted therapeutically to prevent and/or treat these disorders.
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Affiliation(s)
- Charlotte A. Alemao
- Priority Research Centre for Healthy Lungs Hunter Medical Research Institute New Lambton, Newcastle NSW Australia
- The University of Newcastle Newcastle NSW Australia
| | - Kurtis F. Budden
- Priority Research Centre for Healthy Lungs Hunter Medical Research Institute New Lambton, Newcastle NSW Australia
- The University of Newcastle Newcastle NSW Australia
| | - Henry M. Gomez
- Priority Research Centre for Healthy Lungs Hunter Medical Research Institute New Lambton, Newcastle NSW Australia
- The University of Newcastle Newcastle NSW Australia
| | - Saima F. Rehman
- Priority Research Centre for Healthy Lungs Hunter Medical Research Institute New Lambton, Newcastle NSW Australia
- The University of Newcastle Newcastle NSW Australia
| | - Jacqueline E. Marshall
- Faculty of Science Centre for Inflammation Centenary Institute University of Technology Sydney Sydney NSW Australia
| | - Shakti D. Shukla
- Priority Research Centre for Healthy Lungs Hunter Medical Research Institute New Lambton, Newcastle NSW Australia
- The University of Newcastle Newcastle NSW Australia
| | - Chantal Donovan
- Faculty of Science Centre for Inflammation Centenary Institute University of Technology Sydney Sydney NSW Australia
| | - Samuel C. Forster
- Department of Molecular and Translational Sciences Hudson Institute of Medical Research Centre for Innate Immunity and Infectious Diseases Monash University Clayton VIC Australia
| | - Ian A. Yang
- Thoracic Program The Prince Charles Hospital Metro North Hospital and Health Service Brisbane QLD Australia
- Faculty of Medicine UQ Thoracic Research Centre The University of Queensland Brisbane QLD Australia
| | - Simon Keely
- Hunter Medical Research Institute Priority Research Centre for Digestive Health and Neurogastroenterology University of Newcastle New Lambton Heights NSW Australia
| | - Elizabeth R. Mann
- Lydia Becker Institute of Immunology and Inflammation University of Manchester Manchester UK
- Faculty of Biology Medicine and Health Manchester Collaborative Centre for Inflammation Research Manchester Academic Health Science Centre University of Manchester Manchester UK
| | - Emad M. El Omar
- St George & Sutherland Clinical School Microbiome Research Centre University of New South Wales Sydney NSW Australia
| | - Gabrielle T. Belz
- Diamantina Institute University of Queensland Woolloongabba QLD Australia
- Department of Medical Biology Walter and Eliza Hall Institute of Medical Research University of Melbourne Parkville VIC Australia
| | - Philip M. Hansbro
- Priority Research Centre for Healthy Lungs Hunter Medical Research Institute New Lambton, Newcastle NSW Australia
- The University of Newcastle Newcastle NSW Australia
- Faculty of Science Centre for Inflammation Centenary Institute University of Technology Sydney Sydney NSW Australia
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35
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Mu Q, Sun Y, Guo A, Xu X, Qin B, Cai A. A bifunctionalized NiCo 2O 4-Au composite: Intrinsic peroxidase and oxidase catalytic activities for killing bacteria and disinfecting wound. JOURNAL OF HAZARDOUS MATERIALS 2021; 402:123939. [PMID: 33254828 DOI: 10.1016/j.jhazmat.2020.123939] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 08/22/2020] [Accepted: 09/02/2020] [Indexed: 06/12/2023]
Abstract
A NiCo2O4-Au composite was fabricated following the calcination-reduction method and testified to exhibit the intrinsic high peroxidase- and oxidase-like activities. The composite could activate a low level of H2O2 (100 μM) to kill E. coli and S. aureus. NiCo2O4-Au composite could be easily separated by an external magnet from the media and reused several times. NiCo2O4-Au composite could also effectively damage the existing biofilms and prevent the formation of new biofilms. The electron spin resonance tests showed that NiCo2O4-Au composite catalyzed H2O2 into reactive oxygen species (ROS), mainly including OH, O2-, and 1O2; while the oxidase-like activity of NiCo2O4-Au also stemmed from the ROS formation in the absence of H2O2. The radical trapping experiment confirmed that OH and 1O2 were the main radicals in the antibacterial process for NiCo2O4-Au in the presence of H2O2. A NiCo2O4-Au based Band-Aid was also designed, which exhibited high anti-infective and wound-healing properties. This study has demonstrated that NiCo2O4-Au composite can be a promising antibacterial agent in environmental and clinical applications.
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Affiliation(s)
- Qianzhu Mu
- College of Agronomy and Biotechnology, Hebei Normal University of Science & Technology, Qinhuangdao 066600, PR China
| | - Yanfeng Sun
- Ocean College, Hebei Agricultural University, Qinhuangdao 066003, PR China.
| | - Aiying Guo
- College of Agronomy and Biotechnology, Hebei Normal University of Science & Technology, Qinhuangdao 066600, PR China
| | - Xiaoyue Xu
- College of Agronomy and Biotechnology, Hebei Normal University of Science & Technology, Qinhuangdao 066600, PR China
| | - Baoping Qin
- College of Agronomy and Biotechnology, Hebei Normal University of Science & Technology, Qinhuangdao 066600, PR China
| | - Aijun Cai
- College of Agronomy and Biotechnology, Hebei Normal University of Science & Technology, Qinhuangdao 066600, PR China.
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36
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Haldar K, George L, Wang Z, Mistry V, Ramsheh MY, Free RC, John C, Reeve NF, Miller BE, Tal-Singer R, Webb AJ, Brookes AJ, Tobin MD, Singh D, Donaldson GC, Wedzicha JA, Brown JR, Barer MR, Brightling CE. The sputum microbiome is distinct between COPD and health, independent of smoking history. Respir Res 2020; 21:183. [PMID: 32664956 PMCID: PMC7362436 DOI: 10.1186/s12931-020-01448-3] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Accepted: 07/08/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Airway bacterial dysbiosis is a feature of chronic obstructive pulmonary disease (COPD). However, there is limited comparative data of the lung microbiome between healthy smokers, non-smokers and COPD. METHODS We compared the 16S rRNA gene-based sputum microbiome generated from pair-ended Illumina sequencing of 124 healthy subjects (28 smokers and 96 non-smokers with normal lung function), with single stable samples from 218 COPD subjects collected from three UK clinical centres as part of the COPDMAP consortium. RESULTS In healthy subjects Firmicutes, Bacteroidetes and Actinobacteria were the major phyla constituting 88% of the total reads, and Streptococcus, Veillonella, Prevotella, Actinomyces and Rothia were the dominant genera. Haemophilus formed only 3% of the healthy microbiome. In contrast, Proteobacteria was the most dominant phylum accounting for 50% of the microbiome in COPD subjects, with Haemophilus and Moraxella at genus level contributing 25 and 3% respectively. There were no differences in the microbiome profile within healthy and COPD subgroups when stratified based on smoking history. Principal coordinate analysis on operational taxonomic units showed two distinct clusters, representative of healthy and COPD subjects (PERMANOVA, p = 0·001). CONCLUSION The healthy and COPD sputum microbiomes are distinct and independent of smoking history. Our results underline the important role for Gammaproteobacteria in COPD.
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Affiliation(s)
- Koirobi Haldar
- Institute for Lung Health, NIHR, BRC, Department of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK
| | - Leena George
- Institute for Lung Health, NIHR, BRC, Department of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK
| | - Zhang Wang
- Institute of Ecological Science, School of Life Science, South China Normal University, Guangzhou, 510631, China
| | - Vijay Mistry
- Institute for Lung Health, NIHR, BRC, Department of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK
| | - Mohammadali Yavari Ramsheh
- Institute for Lung Health, NIHR, BRC, Department of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK
| | - Robert C Free
- Institute for Lung Health, NIHR, BRC, Department of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK
| | - Catherine John
- Department of Health Sciences, NIHR, BRC, University of Leicester, Leicester, LE1 7RH, UK
| | - Nicola F Reeve
- Department of Health Sciences, NIHR, BRC, University of Leicester, Leicester, LE1 7RH, UK
| | | | | | - Adam J Webb
- Department of Genetics, University of Leicester, Leicester, LE1 7RH, UK
| | - Anthony J Brookes
- Department of Genetics, University of Leicester, Leicester, LE1 7RH, UK
| | - Martin D Tobin
- Department of Health Sciences, NIHR, BRC, University of Leicester, Leicester, LE1 7RH, UK
| | - Dave Singh
- University of Manchester and University Hospital of South Manchester, Manchester, M23 9QZ, UK
| | - Gavin C Donaldson
- National Heart and Lung Institute, Imperial College London, London, SW3 6NP, UK
| | - Jadwiga A Wedzicha
- National Heart and Lung Institute, Imperial College London, London, SW3 6NP, UK
| | - James R Brown
- Computational Biology, Human Genetics, Research and Development (R&D), GlaxoSmithKline (GSK), Collegeville, PA, 19426, USA
| | - Michael R Barer
- Institute for Lung Health, NIHR, BRC, Department of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK
| | - Christopher E Brightling
- Institute for Lung Health, NIHR, BRC, Department of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK.
- Institute for Lung Health, University Hospitals of Leicester, Groby Road, Leicester, LE3 9QP, UK.
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37
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Oehlers SH, Hortle E, Cook KM. A zebrafish model of tuberculosis comorbidity and the effects of HIF-activating intervention. FEBS J 2020; 287:3917-3920. [PMID: 32652856 DOI: 10.1111/febs.15463] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 06/22/2020] [Indexed: 01/12/2023]
Abstract
Comorbidities are an important factor in tuberculosis pathophysiology and treatment but are understudied in animal models. Schild et al. present a zebrafish model of Mycobacterium marinum infection and wound comorbidity that retains responsiveness to protective hypoxia-inducible factor-1α activation as an example of a host-directed therapy. This platform is a new paradigm for the zebrafish-M. marinum infection model and provides a blueprint to test therapeutic interventions on infection and comorbid pathologies. Comment on: https://doi.org/10.1111/febs.15433.
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Affiliation(s)
- Stefan H Oehlers
- The University of Sydney, Tuberculosis Research Program at the Centenary Institute, Camperdown, NSW, Australia.,The University of Sydney, Faculty of Medicine and Health & Marie Bashir Institute, Camperdown, NSW, Australia
| | - Elinor Hortle
- The University of Sydney, Tuberculosis Research Program at the Centenary Institute, Camperdown, NSW, Australia.,The University of Sydney, Faculty of Medicine and Health & Marie Bashir Institute, Camperdown, NSW, Australia
| | - Kristina M Cook
- The University of Sydney, Faculty of Medicine and Health & Charles Perkins Centre, Camperdown, NSW, Australia
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38
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GPNMB contributes to a vicious circle for chronic obstructive pulmonary disease. Biosci Rep 2020; 40:225097. [PMID: 32478378 PMCID: PMC7308735 DOI: 10.1042/bsr20194459] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 05/15/2020] [Accepted: 05/26/2020] [Indexed: 12/13/2022] Open
Abstract
Osteoporosis (OP) is significant and debilitating comorbidity of chronic obstructive pulmonary disease (COPD). We hypothesize that genetic variance identified with OP may also play roles in COPD. We have conducted a large-scale relation data analysis to explore the genes implicated with either OP or COPD, or both. Each gene linked to OP but not to COPD was further explored in a mega-analysis and partial mega-analysis of 15 independently collected COPD RNA expression datasets, followed by gene set enrichment analysis (GSEA) and literature-based pathway analysis to explore their functional linked to COPD. A multiple linear regression (MLR) model was built to study the possible influence of sample size, population region, and study date on the gene expression data in COPD. At the first step of the analysis, we have identified 918 genes associated with COPD, 581 with OP, and a significant overlap (P<2.30e-140; 210 overlapped genes). Partial mega-analysis showed that, one OP gene, GPNMB presented significantly increased expression in COPD patients (P-value = 0.0018; log fold change = 0.83). GPNMB was enriched in multiple COPD pathways and plays roles as a gene hub formulating multiple vicious COPD pathways included gene MMP9 and MYC. GPNMB could be a novel gene that plays roles in both COPD and OP. Partial mega-analysis is valuable in identify case-specific genes for COPD.
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