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Zhang X, Zhou Z, Yang X, Huang L, Wang Q, Chen Y, Du K, Peng J. Inhalable lipid-based nanocarriers covered by polydopamine for effective mucus penetration and pulmonary retention. Colloids Surf B Biointerfaces 2025; 251:114576. [PMID: 39985918 DOI: 10.1016/j.colsurfb.2025.114576] [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: 12/22/2024] [Revised: 02/09/2025] [Accepted: 02/17/2025] [Indexed: 02/24/2025]
Abstract
To overcome the critical challenge in drug inhalation for pulmonary diseases, we innovatively proposed that polydopamine (PDA) as a surface modification material had great potential to improve the mucus permeation and pulmonary retention of inhalable lipid-based nanocarriers. We prepared PDA coated lipid nanoemulsions/solid lipid nanoparticles/liposomes and systematically evaluated their interactions with mucin and pulmonary retention after inhalation. PDA-coated lipid-based nanocarriers exhibited weaker interactions with mucins, higher mucus permeability and cellular uptake by the respiratory epithelium cells compared to PEGylated lipid-based nanocarriers. However, the pulmonary retention advantage of PDA coating was shown in lipid nanoemulsions (< 50 nm) and solid lipid nanoparticles (< 100 nm). Liposomes (∼ 150 nm) with PEGylation possessed higher pulmonary retention than that coated by PDA. It was suggested that PEGylated liposomes were liable to be phagocytosed by alveolar macrophages due to binding with specific antibodies. Overall, this work suggests that PDA as a surface modification material of inhalable lipid-based nanocarriers holds promise for effective mucus penetration and pulmonary retention.
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Affiliation(s)
- Xiaobo Zhang
- State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang 561113, China
| | - Zhengli Zhou
- State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang 561113, China
| | - Xiaohui Yang
- State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang 561113, China
| | - Lei Huang
- State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang 561113, China
| | - Qin Wang
- State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang 561113, China
| | - Yi Chen
- State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang 561113, China.
| | - Kesi Du
- State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang 561113, China.
| | - Jianqing Peng
- State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang 561113, China.
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Chen Q, Xie L, Wang J, Su X, Ye X, Lin X. Resveratrol inhibits lipopolysaccharide‑induced MUC5AC expression and airway inflammation via MAPK and Nrf2 pathways in human bronchial epithelial cells and an acute inflammatory mouse model. Mol Med Rep 2025; 31:157. [PMID: 40211706 PMCID: PMC12004211 DOI: 10.3892/mmr.2025.13522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Accepted: 02/06/2025] [Indexed: 04/16/2025] Open
Abstract
Pathological mucus hypersecretion is an important clinical hallmark of chronic airway inflammatory diseases and yet there is a lack of effective therapeutic medicine. Resveratrol, a dietary polyphenol, has been shown to possess anti‑aging, antioxidation, anti‑inflammation and tumor prevention effects. However, the effect and underlying mechanism of resveratrol in lipopolysaccharide (LPS) induced‑mucus hypersecretion remain to be elucidated. Among more than 20 mucin family members, mucin 5ac (MUC5AC) is a major glycoprotein in airway mucus. The present study investigated the therapeutic effects and mechanisms of resveratrol in LPS‑induced MUC5AC expression in human bronchial epithelial (NCI‑H292) cells and an acute inflammatory murine model. It found that resveratrol markedly attenuated LPS‑induced MUC5AC expression and reactive oxygen species production in NCI‑H292 cells. Moreover, resveratrol increased activation of nuclear factor erythroid‑2‑related factor 2 (Nrf2) and phosphorylation of mitogen‑activated protein kinase (MAPK). Notably, compared with negative control, knockdown of Nrf2 by small interfering RNA and specific inhibitors of ERK/p38 MAPK markedly abrogated the downregulative effect of resveratrol on LPS‑induced MUC5AC expression in NCI‑H292 cells. Additionally, in vivo effects on histopathology and gene expression were assessed in lung tissues collected after intratracheal instillation of LPS with or without resveratrol treatment. Western blotting of lung tissue samples confirmed that administration of resveratrol inhibited MUC5AC expression in LPS‑induced acute inflammatory mice, but increased Nrf2 expression along with phosphorylation of ERK and p38. Periodic acid‑Schiff's staining also showed that resveratrol suppressed mucin production. Compared with the LPS group, administration of resveratrol effectively decreased the numbers of inflammatory cells and neutrophils in bronchoalveolar lavage fluid, as well as markedly alleviating the infiltration of exacerbated inflammatory cells in lung tissue. In conclusion, resveratrol exerted protective effects against LPS‑induced MUC5AC overexpression, inflammation and oxidative stress by activating ERK/p38 MAPK and Nrf2 pathway. Furthermore, the results suggested that resveratrol might be a potential therapeutic agent to inhibit airway mucus hyperproduction.
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Affiliation(s)
- Qiaojuan Chen
- The Second Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350012, P.R. China
- Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
| | - Liutian Xie
- Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
- Graduate School, Fujian Medical University, Fuzhou, Fujian 350122, P.R. China
- Pulmonary Medicine Center of Fujian Province, Quanzhou, Fujian 362000, P.R. China
| | - Jianming Wang
- Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
- Pulmonary Medicine Center of Fujian Province, Quanzhou, Fujian 362000, P.R. China
- Department of Intensive Care Unit, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
| | - Xiaoshan Su
- Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
- Pulmonary Medicine Center of Fujian Province, Quanzhou, Fujian 362000, P.R. China
| | - Xiangjia Ye
- Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
- Pulmonary Medicine Center of Fujian Province, Quanzhou, Fujian 362000, P.R. China
| | - Xiaoping Lin
- Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
- Pulmonary Medicine Center of Fujian Province, Quanzhou, Fujian 362000, P.R. China
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3
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Liu S, Ge J, Liu W, Zhuang Z, Liu S. Involvement of the somatosensory-autonomic reflex and muscarinic receptors in exacerbation of allergic pulmonary inflammation by electroacupuncture. Br J Pharmacol 2025; 182:2374-2391. [PMID: 39923815 DOI: 10.1111/bph.17415] [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: 07/16/2024] [Revised: 10/14/2024] [Accepted: 10/25/2024] [Indexed: 02/11/2025] Open
Abstract
BACKGROUND AND PURPOSE Emerging evidence suggests that electroacupuncture (EA) could cause autonomic reflexes to modulate visceral functions. However, the efficacy and underlying mechanisms for somatic stimulation on allergic pulmonary inflammation (API) remain elusive. EXPERIMENTAL APPROACH Mice were administered intranasal Papain to induce API. Distinct current (0,0.1, 0.2 and 0.5 mA) of EA at the back BL13, hindlimb ST36 and forelimb LU5 acupoint were then carried out. The control group underwent the same procedure but without current stimulation. Changes in API was assessed using immunohistochemistry, flow cytometry and haematoxylin and eosin (H&E) staining. Pharmacological approaches were used to investigate the underlying mechanisms of EA effects on API. KEY RESULTS EA at the back region but not limb regions, in a current intensity-dependent manner, exacerbated API, primarily causing a decrease in the survival rate and intensified inflammation in the lung, including the infiltration of lung type 2 innate lymphoid cells and eosinophils, and lung pathology scores. Blocking local thoracic sensory nerves with lidocaine or lung-innervated autonomic nerves with hexamethonium eliminates the EA-produced detrimental effects. Chemical pulmonary sympathectomy with 6-OHDA further enhanced lung pathology scores, but inhibiting the activity of pulmonary muscarinic receptors was sufficient to prevent the exacerbation of API induced by EA. CONCLUSION AND IMPLICATIONS Our findings suggest that BL13 EA induces a somatic-autonomic reflex involving the pulmonary muscarinic receptors, thereby exacerbating API. The selective and intensity-dependency activation of body thoracic regions in driving pulmonary autonomic pathways could help optimise stimulation parameters, enhancing both efficacy and safety in modulating API.
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Affiliation(s)
- Shuyan Liu
- State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Huashan Hospital, Fudan University, Shanghai, China
| | - Jiayi Ge
- State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Huashan Hospital, Fudan University, Shanghai, China
| | - Weili Liu
- State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Huashan Hospital, Fudan University, Shanghai, China
| | - Zhidi Zhuang
- State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Huashan Hospital, Fudan University, Shanghai, China
| | - Shenbin Liu
- State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Huashan Hospital, Fudan University, Shanghai, China
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Wei S, Zhai Z, Kong X, Wu C, Zhu B, Zhao Z, Zhang X. The review of nasal drug delivery system: The strategies to enhance the efficiency of intranasal drug delivery by improving drug absorption. Int J Pharm 2025; 676:125584. [PMID: 40216038 DOI: 10.1016/j.ijpharm.2025.125584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 04/02/2025] [Accepted: 04/08/2025] [Indexed: 04/15/2025]
Abstract
Nasal drug administration constitutes an efficient and non-invasive modality of drug delivery, and its distinctive physiological structure offers potentialities for treating a variety of diseases. To elevate the drug absorption and delivery efficiency, it is of paramount importance to delineate the transport routes and their enhancement mechanisms. Nevertheless, drug absorption pathways vary depending on the disease target, these variations present opportunities for targeted delivery and challenges for achieving precision. Hence, this review outlines the anatomical structure of the nasal cavity, and subsequently elaborates on the drug transport pathways within the nasal cavity and their influencing factors. Based on the distinct sites of drug action, diseases suitable for nasal drug administration are categorized into three types: systemic diseases, local nasal diseases, and central nervous system diseases. Grounded on multiple transport routes and their influencing factors, this review proposes strategies like optimizing formulation viscosity, using penetration enhancers, adding mucosal adhesives and improving delivery device, offering insights into future advancements in nasal drug delivery systems.
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Affiliation(s)
- Shuhua Wei
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510006, PR China
| | - Zizhao Zhai
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510006, PR China
| | - Xi Kong
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510006, PR China
| | - Chuanbin Wu
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510006, PR China
| | - Bing Zhu
- Respirent Pharmaceuticals Co. Ltd., Chongqing 40070, PR China.
| | - Ziyu Zhao
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510006, PR China; State Key Laboratory of Bioactive Molecules and Druggability Assessment, College of Pharmacy, Jinan University, Guangzhou 511443, PR China.
| | - Xuejuan Zhang
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510006, PR China.
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5
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Plenge M, Schnepel N, Müsken M, Rohde J, Goethe R, Breves G, Mazzuoli-Weber G, Benz P. Development and characterization of a 2D porcine colonic organoid model for studying intestinal physiology and barrier function. PLoS One 2025; 20:e0312989. [PMID: 40333830 PMCID: PMC12057940 DOI: 10.1371/journal.pone.0312989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Accepted: 04/03/2025] [Indexed: 05/09/2025] Open
Abstract
The porcine colon epithelium plays a crucial role in nutrient absorption, ion transport, and barrier function. However ethical concerns necessitate the development of alternatives to animal models for its study. The objective of this study was to develop and characterize a two-dimensional (2D) in vitro model of porcine colonic organoids that closely mimics native colon tissue, thereby supporting in vitro research in gastrointestinal physiology, pathology, and pharmacology. Porcine colonic crypts were isolated and cultured in three-dimensional (3D) organoid systems, which were subsequently disaggregated to form 2D monolayers on transwell inserts. The integrity of the monolayers was evaluated through the measurement of transepithelial electrical resistance (TEER) and electron microscopy. The functional prerequisites of the model were evaluated through the measurement of the mRNA expression of key ion channels and transporters, using quantitative RT-PCR. Ussing chamber experiments were performed to verify physiological activity. The 2D monolayer displayed robust TEER values and retained structural characteristics, including microvilli and mucus-secreting goblet cells, comparable to those observed in native colon tissue. Gene expression analysis revealed no significant differences between the 2D organoid model and native tissue with regard to critical transporters. Ussing chamber experiments demonstrated physiological responses that were consistent with those observed in native colonic tissue. In conclusion, 2D porcine colonic organoid model can be recommended as an accurate representation of the physiological and functional attributes of the native colon epithelium. This model offers a valuable tool for investigating intestinal barrier properties, ion transport, and the pathophysiology of gastrointestinal diseases, while adhering to the 3R principles.
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Affiliation(s)
- Masina Plenge
- Institute for Physiology and Cell Biology, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Nadine Schnepel
- Institute for Physiology and Cell Biology, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Mathias Müsken
- Central Facility for Microscopy, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - Judith Rohde
- Institute of Microbiology, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Ralph Goethe
- Institute of Microbiology, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Gerhard Breves
- Institute for Physiology and Cell Biology, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Gemma Mazzuoli-Weber
- Institute for Physiology and Cell Biology, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Pascal Benz
- Institute for Physiology and Cell Biology, University of Veterinary Medicine Hannover, Hannover, Germany
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Zavvar F, Mazandarani M, Hoseinifar SH, Jafari V, Lieke T. Effects of Feed Supplementation With Fulvic Acid on the Systemic and Mucosal Protective Mechanisms of Juvenile Rainbow Trout (Oncorhynchus mykiss). J Anim Physiol Anim Nutr (Berl) 2025; 109:834-843. [PMID: 39806798 DOI: 10.1111/jpn.14100] [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: 07/25/2024] [Revised: 11/21/2024] [Accepted: 12/28/2024] [Indexed: 01/16/2025]
Abstract
Rainbow trout (Oncorhynchus mykiss) is an important fish species raised in aquaculture, but it is susceptible to stress, infections diseases. The present study aimed to determine the effects of fulvic acid feed addition on the systemic and mucosal protective mechanisms of juvenile rainbow trout and to elucidate the underlying molecular mechanisms of changes in the gut. Rainbow trout (4.30 ± 0.6 g) diet was supplemented with different levels of fulvic acid: 0% (Control), 0.5%, 1% and 2%. At the end of 8-week feeding trial, growth parameters such as final weight gained weight (%), SGR (F1%) increased, and FCR (all levels) decreased significantly compared to the control group. We found that the activity of lysozyme, glutathione peroxidase, and catalase in the serum were significantly improved, especially after the addition of 0.5% and 1% of fulvic acid. At the same time, the immunoglobulin concentration in the skin mucus was increased with 0.5% supplementation. However, the expression of tnf-α, il-6 and gpx in the intestine was strongly upregulated after supplementation with 2%, indicating oxidative stress and inflammation with this level of fulvic acid inclusion. Furthermore, the mucus lysozyme activity was reduced at this concentration, which can increase the susceptibility to pathogen invasion. The results suggest that adding 0.5%-1% of fulvic acid to the feed of juvenile rainbow trout can help to improve their immune and antioxidative defenses and thereby support the wellbeing of fish.
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Affiliation(s)
- Fatemeh Zavvar
- Department of Fisheries, Faculty of Fisheries and Environmental Sciences, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran
| | - Mohammad Mazandarani
- Department of Fisheries, Faculty of Fisheries and Environmental Sciences, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran
| | - Seyed Hossein Hoseinifar
- Department of Fisheries, Faculty of Fisheries and Environmental Sciences, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran
| | - Valiollah Jafari
- Department of Fisheries, Faculty of Fisheries and Environmental Sciences, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran
| | - Thora Lieke
- Faculty of Fisheries and Protection of Waters, South Bohemian Research Centre of Aquaculture and Biodiversity of Hydrocenoses, Institute of Aquaculture and Protection of Waters, University of South Bohemia, České Budějovice, Czech Republic
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7
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Cheong KL, Chen W, Wang M, Zhong S, Veeraperumal S. Therapeutic Prospects of Undaria pinnatifida Polysaccharides: Extraction, Purification, and Functional Activity. Mar Drugs 2025; 23:163. [PMID: 40278284 PMCID: PMC12028517 DOI: 10.3390/md23040163] [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: 03/02/2025] [Revised: 03/28/2025] [Accepted: 04/07/2025] [Indexed: 04/26/2025] Open
Abstract
Undaria pinnatifida, an edible brown seaweed that is widely consumed in East Asia, has gained increasing recognition for its health benefits. Among its bioactive compounds, polysaccharides have attracted significant attention due to their diverse biological activity. This review provides a comprehensive overview of recent advancements in the extraction, purification, structural characterization, and bioactivity of U. pinnatifida polysaccharides. We discuss state-of-the-art extraction techniques, including ultrasound-assisted, microwave-assisted, and enzyme-assisted extraction, as well as purification strategies such as membrane separation and chromatographic methods. Furthermore, we highlight their potential biological activity, including antioxidant, immunomodulatory, anticancer, gut health-promoting, and anti-hyperglycemic effects, along with their underlying mechanisms of action. By summarizing the latest research, this review aims to provide valuable insights into the development and application of U. pinnatifida polysaccharides in functional foods and pharmaceuticals.
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Affiliation(s)
- Kit-Leong Cheong
- Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; (K.-L.C.); (W.C.)
| | - Wenjie Chen
- Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; (K.-L.C.); (W.C.)
| | - Min Wang
- College of Coastal Agriculture Sciences, Guangdong Ocean University, Zhanjiang 524088, China;
| | - Saiyi Zhong
- Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China; (K.-L.C.); (W.C.)
| | - Suresh Veeraperumal
- Department of Biology, College of Science, Shantou University, Shantou 515063, China
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8
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Blitzer GC, Paz C, McCoy SS, Kimple RJ. Radiation-Therapy Related Salivary Dysfunction. Semin Radiat Oncol 2025; 35:278-284. [PMID: 40090753 PMCID: PMC11911547 DOI: 10.1016/j.semradonc.2025.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Accepted: 02/16/2025] [Indexed: 03/18/2025]
Abstract
Radiation-induced xerostomia (RIX) is a common and debilitating side effect of head and neck cancer radiotherapy, significantly impacting patients' quality of life. This review comprehensively summarizes the current understanding of RIX, encompassing its clinical quantification, underlying pathophysiology, and established and emerging treatment modalities. We explore various objective and subjective measures used to quantify salivary flow and assess the severity of xerostomia in clinical settings. The pathophysiological mechanisms leading to RIX are elucidated, including radiation damage to salivary glands, alterations in saliva composition, and the role of inflammatory processes. Current treatment strategies, such as saliva substitutes and stimulants, are discussed alongside their limitations. Furthermore, we delve into novel investigational approaches, including gene therapy, stem cell transplantation, and pharmacologic interventions, offering promising avenues for future RIX management. This review provides clinicians and researchers with a comprehensive overview of RIX, highlighting the need for continued research to develop more effective preventative and therapeutic strategies to alleviate this burdensome condition.
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Affiliation(s)
- Grace C Blitzer
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI.; University of Wisconsin Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Cristina Paz
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Sara S McCoy
- University of Wisconsin Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI.; Department of Medicine, Division of Rheumatology, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Randall J Kimple
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI.; University of Wisconsin Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI..
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9
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Dorscheid D, Gauvreau GM, Georas SN, Hiemstra PS, Varricchi G, Lambrecht BN, Marone G. Airway epithelial cells as drivers of severe asthma pathogenesis. Mucosal Immunol 2025:S1933-0219(25)00029-7. [PMID: 40154790 DOI: 10.1016/j.mucimm.2025.03.003] [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: 05/20/2024] [Revised: 01/31/2025] [Accepted: 03/19/2025] [Indexed: 04/01/2025]
Abstract
Our understanding of the airway epithelium's role in driving asthma pathogenesis has evolved over time. From being regarded primarily as a physical barrier that could be damaged via inflammation, the epithelium is now known to actively contribute to asthma development through interactions with the immune system. The airway epithelium contains multiple cell types with specialized functions spanning barrier action, mucociliary clearance, immune cell recruitment, and maintenance of tissue homeostasis. Environmental insults may cause direct or indirect injury to the epithelium leading to impaired barrier function, epithelial remodelling, and increased release of inflammatory mediators. In severe asthma, the epithelial barrier repair process is inhibited and the response to insults is exaggerated, driving downstream inflammation. Genetic and epigenetic mechanisms also maintain dysregulation of the epithelial barrier, adding to disease chronicity. Here, we review the role of the airway epithelium in severe asthma and how targeting the epithelium can contribute to asthma treatment.
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Affiliation(s)
- Del Dorscheid
- Centre for Heart Lung Innovation, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Gail M Gauvreau
- Division of Respirology, Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Steve N Georas
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Pieter S Hiemstra
- Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands
| | - Gilda Varricchi
- Department of Translational Medical Sciences (DiSMeT) and Center for Basic and Clinical Immunology Research (CISI), School of Medicine, University of Naples Federico II, Naples, Italy; Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, Naples, Italy
| | - Bart N Lambrecht
- Center for Inflammation Research, Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
| | - Gianni Marone
- Department of Translational Medical Sciences (DiSMeT) and Center for Basic and Clinical Immunology Research (CISI), School of Medicine, University of Naples Federico II, Naples, Italy; Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council, Naples, Italy.
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10
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Ye B, Teng S, Zhan L. The Link Between Respiratory Syncytial Virus-Induced Lower Respiratory Tract Infection and Type 2 Inflammation in Asthma. Clin Pediatr (Phila) 2025:99228251321597. [PMID: 40126358 DOI: 10.1177/00099228251321597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/25/2025]
Abstract
OBJECTIVE To investigate the relationship between the type 2 inflammatory response associated with asthma and lower respiratory tract infection (LRTI) caused by respiratory syncytial virus (RSV). METHODS Sixty-seven children with RSV infection hospitalized in our hospital from October 2023 to December 2023 and 27 healthy children undergoing medical examination were included. The study population was divided into the RSV LRTI group (n = 67) and the control group (n = 27). Interleukin-13 (IL-13), serum total immunoglobulin E (IgE), mucin 5AC (MUC5AC), and blood eosinophil count (EOS) were tested and compared between the two groups. The presence or absence of specificity between the two groups was analyzed using the rank sum test and subject operating characteristic curves (Receiver Operating Characteristic curves, ROC curves). RESULTS The levels of IL-13, IgE, MUC5AC, and EOS were higher in children with RSV LRTI compared to healthy children. These differences were statistically significant (P < .05). The ROC curve analysis results showed that IL-13, IgE, MUC5AC, and EOS predicted type 2 inflammation with areas under the curve of 0.687, 0.762, 0.764, and 0.646, respectively. CONCLUSION A type 2 inflammatory response associated with asthma may be observed after RSV-induced LRTIs.
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Affiliation(s)
- Bei Ye
- Hangzhou Children's Hospital, Hangzhou, China
| | - Shu Teng
- Hangzhou Children's Hospital, Hangzhou, China
| | - Lu Zhan
- Hangzhou Red Cross Hospital, Hangzhou, China
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11
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Lew SQ, Chong SY, Lau GW. Modulation of pulmonary immune functions by the Pseudomonas aeruginosa secondary metabolite pyocyanin. Front Immunol 2025; 16:1550724. [PMID: 40196115 PMCID: PMC11973339 DOI: 10.3389/fimmu.2025.1550724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Accepted: 03/05/2025] [Indexed: 04/09/2025] Open
Abstract
Pseudomonas aeruginosa is a prevalent opportunistic Gram-negative bacterial pathogen. One of its key virulence factors is pyocyanin, a redox-active phenazine secondary metabolite that plays a crucial role in the establishment and persistence of chronic infections. This review provides a synopsis of the mechanisms through which pyocyanin exacerbates pulmonary infections. Pyocyanin induces oxidative stress by generating reactive oxygen and nitrogen species which disrupt essential defense mechanisms in respiratory epithelium. Pyocyanin increases airway barrier permeability and facilitates bacterial invasion. Pyocyanin also impairs mucociliary clearance by damaging ciliary function, resulting in mucus accumulation and airway obstruction. Furthermore, it modulates immune responses by promoting the production of pro-inflammatory cytokines, accelerating neutrophil apoptosis, and inducing excessive neutrophil extracellular trap formation, which exacerbates lung tissue damage. Additionally, pyocyanin disrupts macrophage phagocytic function, hindering the clearance of apoptotic cells and perpetuating inflammation. It also triggers mucus hypersecretion by inactivating the transcription factor FOXA2 and enhancing the IL-4/IL-13-STAT6 and EGFR-AKT/ERK1/2 signaling pathways, leading to goblet cell metaplasia and increased mucin production. Insights into the role of pyocyanin in P. aeruginosa infections may reveal potential therapeutic strategies to alleviate the severity of infections in chronic respiratory diseases including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
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Affiliation(s)
| | | | - Gee W. Lau
- Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, IL, United States
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Zhu L, Luo Y, Liu Y, Sun S, Yuan J, Zhang L, Zhong W, Ma S, Yu Z, Zhou J, Chen X, Zhao J. Clostridium butyricum ameliorates indomethacin-induced enteropathy by promoting MUC2 secretion via suppressing the Notch pathway. Front Microbiol 2025; 16:1509876. [PMID: 40177488 PMCID: PMC11961966 DOI: 10.3389/fmicb.2025.1509876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Accepted: 03/04/2025] [Indexed: 04/05/2025] Open
Abstract
Nonsteroidal anti-inflammatory drug (NSAID) enteropathy is a serious clinical complication with no effective treatments available. Modulating the intestinal microbiota through dietary and nutritional targets is a promising strategy for preventing NSAID enteropathy. This study aimed to investigate the protective effect and underlying mechanisms of the probiotic Clostridium butyricum (CB) on indomethacin (IND)-induced enteropathy. C57BL/6J mice received CB treatment for 14 days along with concurrent IND gavage for the final 7 days. Caco2 cells were stimulated with IND to evaluate the effect of CB supernatant (CBS) on the intestinal barrier function, and LS174T cells were used to validate the modulatory action of CBS on the Notch signaling pathway. Our findings revealed that CB treatment prevented anorexia and weight loss, reduced the severity of enteropathy, and decreased the inflammatory response of the small intestine. CB also increased the expression of tight junction proteins and reduced permeability in mice and Caco2 cells. Additionally, CB suppressed apoptosis and promoted proliferation in the small intestine. Further research found that CB increased the number of goblet cells and MUC2 secretion. Mechanistically, CB may promote MUC2 secretion by suppressing the Notch signaling pathway, consistent with the results of intervention in LS174T cells with CBS. In conclusion, CB might prevent NSAID enteropathy by increasing MUC2 secretion through the inhibition of the Notch pathway. Our study identified the potential efficacy of CB as a preventive strategy against NSAID enteropathy and showed promising prospects for CB as a food supplement.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Xin Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Jingwen Zhao
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin, China
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Wei Y, Ma J. Effective-Component Compatibility of Bufei Yishen Formula (ECC-BYF) III Inhibits Mucus Hypersecretion by BEAS-2B Cells via miR-146a-5p-Mediated Regulation of the EGFR/MEK/ERK Pathway. Int J Chron Obstruct Pulmon Dis 2025; 20:623-639. [PMID: 40092321 PMCID: PMC11908394 DOI: 10.2147/copd.s498477] [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: 09/28/2024] [Accepted: 02/18/2025] [Indexed: 03/19/2025] Open
Abstract
Purpose To explore the role of the miR-146a-5p-mediated regulation of the EGFR/MEK/ERK pathway in the effect of effective-component compatibility of Bufei Yishen Formula III (ECC-BYF III) on ameliorating mucus hypersecretion by bronchial epithelial cells (BEAS-2B cells). Methods BEAS-2B cells exposed to cigarette smoke extract (CSE) were used to establish a mucus hypersecretion model of BEAS-2B cells. The optimal intervention concentration of ECC-BYF III was screened by CCK-8, qRT-PCR and ELISA, the effects of ECC-BYF III on MUC5AC, MUC5B, IL-4, IL-8, TNF-α, IL-1α, miR-146a-5p and EGFR/MEK/ERK pathway expression were assessed. Furthermore, dual luciferase reporter gene was used to verify the relationship between miR-146a-5p and EGFR/MEK/ERK, and to observe the effect of down-regulating miR-146a-5p on ECC-BYF III ameliorating mucus hypersecretion and EGFR/MEK/ERK pathway. Results ECC-BYF III reduced the expression of MUC5AC and MUC5B, decreased the mRNA expression of IL-1α, IL-8 and TNF-α, increased the mRNA expression of IL-4, and decreased the protein expression of TNF-α. Moreover, ECC-BYF III ameliorated CSE induced mucus hypersecretion in BEAS-2B cells through EGFR/MEK/ERK pathway. Finally, our results indicated that ECC-BYF III ameliorated the model by targeting miR-146a-5p and downregulating the EGFR/MEK/ERK pathway. Conclusion ECC-BYF III can ameliorate CSE induced mucus hypersecretion by BEAS-2B cells and reduce the inflammatory response. The underlying mechanism may be related to the regulation of miR-146a-5p and the EGFR/MEK/ERK pathway. ECC-BYF III can inhibit activation of the EGFR/MEK/ERK pathway by upregulating the expression of miR-146a-5p, thereby ameliorating mucus hypersecretion by BEAS-2B cells.
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Affiliation(s)
- Yumeng Wei
- Traditional Chinese Medicine (Zhongjing) School, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China
| | - Jindi Ma
- Traditional Chinese Medicine (Zhongjing) School, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China
- Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of People’s Republic of China, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China
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14
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Li M, Li G, Liu Y, Li J, Ou Y, Guan W, Zeng Z, Tang H, Bai D, Zhang G, Huang P, Song L, Ye L, Ke H, Yao H. Design, Synthesis, and Evaluation of Selective PDE4 Inhibitors for the Therapy of Pulmonary Injury. J Med Chem 2025; 68:3837-3857. [PMID: 39847693 DOI: 10.1021/acs.jmedchem.4c02969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2025]
Abstract
Pulmonary inflammation is the main cause of lung injury. Phosphodiesterase 4 (PDE4) is a promising anti-inflammatory target for the treatment of respiratory diseases. Herein, we designed and synthesized 43 compounds in two novel series of benzimidazole derivatives as PDE4 inhibitors. Among them, compound A5 showed highly selective inhibition of PDE4, good safety, and liver microsomal stability in vitro. A5 administration remarkably attenuated inflammatory infiltration and pathologic injury of the lung in models of acute lung injury in mice and chronic obstructive pulmonary disease (COPD) in mice. In addition, A5 enhanced sputum secretion, relieved cough in mice, and inhibited phosphorylation of p38 MAP kinase, an important protein in the regulation of lung injury. Overall, A5, as an effective PDE4 inhibitor without acute toxicity and gastrointestinal reaction, may be a potent candidate for the treatment of pulmonary injury.
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Affiliation(s)
- Mengjie Li
- Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China
| | - Gang Li
- Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China
| | - Yuanhui Liu
- Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China
- School of Pharmacy, Guangdong Pharmaceutical University, Guangdong 510006, China
| | - Jiayu Li
- Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China
| | - Yanghui Ou
- Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China
| | - Wen Guan
- Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China
| | - Zhijun Zeng
- Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China
| | - Haiyang Tang
- State Key Laboratory of Respiratory Disease, Guangzhou Medical University, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China
| | - Dan Bai
- State Key Laboratory of Respiratory Disease, Guangzhou Medical University, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China
| | - Guoping Zhang
- Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China
| | - Peiming Huang
- Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China
| | - Liyan Song
- Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China
| | - Lianbao Ye
- School of Pharmacy, Guangdong Pharmaceutical University, Guangdong 510006, China
| | - Hengming Ke
- Department of Biochemistry and Biophysics, The University of North Carolina, 120 Mason Farm Road, Chapel Hill, North Carolina 27599, United States
| | - Hongliang Yao
- Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China
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de Souza BMS, Guerra LHA, Varallo GR, Taboga SR, Penna ALB. The Impact in Intestines and Microbiota in BALB/c Mice Through Consumption of Milk Fermented by Potentially Probiotic Lacticaseibacillus casei SJRP38 and Limosilactobacillus fermentum SJRP43. Probiotics Antimicrob Proteins 2025; 17:462-478. [PMID: 37796426 DOI: 10.1007/s12602-023-10158-3] [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] [Accepted: 09/12/2023] [Indexed: 10/06/2023]
Abstract
The present study aimed to evaluate the effect of consumption of milk fermented by Lacticaseibacillus (Lc.) casei SJRP38 and Limosilactobacillus (Lm.) fermentum SJRP43 on bacterial translocation, stool analysis, and intestinal morphology of healthy BALB/c mice. Potentially probiotic lactic acid bacteria, Lc. casei SJRP38, and Lm. fermentum SJRP43 were evaluated and analyzed for translocation, fecal analysis, and intestinal morphology of four groups of mice: water control (WC), milk control (MC), milk fermented by Lc. casei SJRP38 (FMLC), and milk fermented by Lm. fermentum SJRP43 (FMLF), in co-culture with Streptococcus thermophilus ST080. The results of the animal assay indicate that the population of Lactobacilli and Bidobacterium sp. in the gastrointestinal tract of BALB/c mice was greater than 6.0 log10 CFU/g, and there was no evidence of bacteremia due to the low incidence of bacterial translocation. Ingesting fermented milk containing Lc. casei SJRP38 and Lm. fermentum SJRP43 was found to promote a healthier microbiota, as it led to a reduction in Clostridium sp. and an increase in Lactobacilli and Bifidobacterium sp. in feces. Furthermore, the dairy treatments (MC, FMLC, and FMLF) resulted in taller intestinal villi and an increase in the frequency of goblet cells in the intestines. Overall, the consumption of fermented milk containing Lc. casei SJRP38 and Lm. fermentum SJRP43 strains was deemed safe and demonstrated beneficial effects on the intestines of BALB/c mice.
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Affiliation(s)
- Bruna Maria Salotti de Souza
- Department of Technology and Inspection of Products of Animal Origin, UFMG - Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil
| | - Luiz Henrique Alves Guerra
- Department of Biology, Institute of Biosciences, Languages and Exact Sciences, UNESP - Sao Paulo State University, São José do Rio Preto, SP, 15054-000, Brazil
| | | | - Sebastião Roberto Taboga
- Department of Biology, Institute of Biosciences, Languages and Exact Sciences, UNESP - Sao Paulo State University, São José do Rio Preto, SP, 15054-000, Brazil
| | - Ana Lúcia Barretto Penna
- Department of Food Engineering and Technology, Institute of Biosciences, Languages and Exact Sciences, UNESP - Sao Paulo State University, São José do Rio Preto, SP, 15054-000, Brazil.
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Ling F, Sahin AT, Naranjo BM, Aime S, Roth D, Tepho N, Vendrame AS, Emken E, Kiechle M, Tesfaigzi Y, Lieleg O, Nawroth J. High-throughput Mucus Microrheology for Phenotyping and Disease Modeling. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.01.09.632077. [PMID: 39868248 PMCID: PMC11761623 DOI: 10.1101/2025.01.09.632077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/28/2025]
Abstract
Mucus plays an integral role for the barrier function of many epithelial tissues. In the human airways, mucus is constantly secreted to capture inhaled microbes and pollutants and cleared away through concerted ciliary motion. Many important respiratory diseases exhibit altered mucus flowability and impaired clearance, contributing to respiratory distress and increased risk of infections. Understanding how mucus rheology changes during disease progression and in response to treatments is thus of great interest for subtyping patients and tailoring treatments, probing disease mechanisms, and tailoring therapies; however, basic research of mucus rheology is greatly hampered by the lack of scalable and user-friendly rheometry assays for the small volumes of mucus typically produced by in vitro respiratory models and in clinical ex vivo settings. To address this challenge, we developed a streamlined, high-throughput protocol leveraging Differential Dynamic Microscopy (DDM) to reliably measure the frequency-dependent microrheology of minuscule (3-10 μL) mucus samples using standard epifluorescence microscopy. Our method does not require time-consuming user-interventions common in particle tracking routines and measures microrheology at the time scale of mucus relaxation (1-20s), hence greatly reducing assay time. We demonstrate the successful application of our method in mucus samples harvested from state-of-the-art air-liquid-interface (ALI) human respiratory cultures to assess mucus rheology in airway disease models and different culture conditions. To show that our approach equally applies to other types and sources of human mucus, we also validated our method with clinical samples of cervical mucus. We envision that our method can be seamlessly adopted by non-expert users, without the need for specialized equipment or extensive training, to study diseases and their treatments in the respiratory, intestinal, reproductive and other mucosal organ systems. This advancement opens up new avenues for large-scale studies, providing new insights into the role of mucus rheology which was previously limited by data accessibility and resource constraints.
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Affiliation(s)
- Feng Ling
- Helmholtz Pioneer Campus and Institute of Biological and Medical Imaging, Helmholtz Munich, 85764 Neuherberg, Germany
- Chair of Biological Imaging at the Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich (TUM), Munich, Germany
| | - Ayse Tugce Sahin
- Helmholtz Pioneer Campus and Institute of Biological and Medical Imaging, Helmholtz Munich, 85764 Neuherberg, Germany
- Chair of Biological Imaging at the Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich (TUM), Munich, Germany
| | - Bernardo Miller Naranjo
- TUM School of Engineering and Design, Department of Materials Engineering, Technical University of Munich (TUM), 85748 Garching, Germany
- Center for Protein Assemblies (CPA) and Munich Institute of Biomedical Engineering (MIBE), Technical University of Munich (TUM), 85748 Garching, Germany
| | - Stefano Aime
- Molecular, Macromolecular Chemistry, and Materials, Ecole Supérieure de Physique et de Chimie Industrielles (ESPCI) Paris, 75005 Paris, France
| | - Doris Roth
- Helmholtz Pioneer Campus and Institute of Biological and Medical Imaging, Helmholtz Munich, 85764 Neuherberg, Germany
- Chair of Biological Imaging at the Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich (TUM), Munich, Germany
| | - Niels Tepho
- Helmholtz Pioneer Campus and Institute of Biological and Medical Imaging, Helmholtz Munich, 85764 Neuherberg, Germany
- Chair of Biological Imaging at the Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich (TUM), Munich, Germany
| | - Andrea S. Vendrame
- Pulmonary Critical Care Medicine Division, Brigham and Women’s Hospital and Harvard Medical School, Harvard University, Boston, Massachusetts, USA
| | - Ellen Emken
- Heinz-Nixdorf-Chair of Biomedical Electronics, School of Computation, Information and Technology, Technical University of Munich (TUM), Germany
| | - Marion Kiechle
- Department of Gynecology, Comprehensive Cancer Center Munich, TUM University Hospital Technical University Munich, Germany
| | - Yohannes Tesfaigzi
- Pulmonary Critical Care Medicine Division, Brigham and Women’s Hospital and Harvard Medical School, Harvard University, Boston, Massachusetts, USA
| | - Oliver Lieleg
- TUM School of Engineering and Design, Department of Materials Engineering, Technical University of Munich (TUM), 85748 Garching, Germany
- Center for Protein Assemblies (CPA) and Munich Institute of Biomedical Engineering (MIBE), Technical University of Munich (TUM), 85748 Garching, Germany
| | - Janna Nawroth
- Helmholtz Pioneer Campus and Institute of Biological and Medical Imaging, Helmholtz Munich, 85764 Neuherberg, Germany
- Chair of Biological Imaging at the Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich (TUM), Munich, Germany
- Comprehensive Pneumology Center (CPC-M), German Center for Lung Research (DZL), 85748 Munich, Germany
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17
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Zhou X, Wu Y, Zhu Z, Lu C, Zhang C, Zeng L, Xie F, Zhang L, Zhou F. Mucosal immune response in biology, disease prevention and treatment. Signal Transduct Target Ther 2025; 10:7. [PMID: 39774607 PMCID: PMC11707400 DOI: 10.1038/s41392-024-02043-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Revised: 09/05/2024] [Accepted: 10/27/2024] [Indexed: 01/11/2025] Open
Abstract
The mucosal immune system, as the most extensive peripheral immune network, serves as the frontline defense against a myriad of microbial and dietary antigens. It is crucial in preventing pathogen invasion and establishing immune tolerance. A comprehensive understanding of mucosal immunity is essential for developing treatments that can effectively target diseases at their entry points, thereby minimizing the overall impact on the body. Despite its importance, our knowledge of mucosal immunity remains incomplete, necessitating further research. The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has underscored the critical role of mucosal immunity in disease prevention and treatment. This systematic review focuses on the dynamic interactions between mucosa-associated lymphoid structures and related diseases. We delve into the basic structures and functions of these lymphoid tissues during disease processes and explore the intricate regulatory networks and mechanisms involved. Additionally, we summarize novel therapies and clinical research advances in the prevention of mucosal immunity-related diseases. The review also addresses the challenges in developing mucosal vaccines, which aim to induce specific immune responses while maintaining tolerance to non-pathogenic microbes. Innovative therapies, such as nanoparticle vaccines and inhalable antibodies, show promise in enhancing mucosal immunity and offer potential for improved disease prevention and treatment.
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Affiliation(s)
- Xiaoxue Zhou
- School of Medicine, Hangzhou City University, Hangzhou, China
- MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, China
| | - Yuchen Wu
- The First School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zhipeng Zhu
- MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, China
| | - Chu Lu
- The First Affiliated Hospital, the Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Chunwu Zhang
- The First School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Linghui Zeng
- School of Medicine, Hangzhou City University, Hangzhou, China
| | - Feng Xie
- The First Affiliated Hospital, the Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
| | - Long Zhang
- MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, China.
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China.
| | - Fangfang Zhou
- The First Affiliated Hospital, the Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
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18
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Wang W, Xia J, Shen Y, Qiao C, Liu M, Cheng X, Mu S, Yan W, Lu W, Gao S, Zhou K. Potential diagnostic biomarkers in heart failure: Suppressed immune-associated genes identified by bioinformatic analysis and machine learning. Eur J Pharmacol 2025; 986:177153. [PMID: 39586393 DOI: 10.1016/j.ejphar.2024.177153] [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: 07/26/2024] [Revised: 11/21/2024] [Accepted: 11/22/2024] [Indexed: 11/27/2024]
Abstract
Heart failure (HF) threatens tens of millions of people's health worldwide, which is the terminal stage in the development of majority cardiovascular diseases. Recently, an increasing number of studies have demonstrated that bioinformatics and machine learning (ML) algorithms can offer new insights into the diagnosing and treating HF. To further discover HF diagnostic genes, we utilized least absolute shrinkage and selection operator (LASSO) and Support Vector Machine (SVM) to identify novel immune-related genes. The HF dataset was obtained from the gene expression omnibus (GEO) database and three candidate genes (LCN6, MUC4, and TNFRSF13C) were finally screened. In addition, the myocardial infarction (MI) modeling experiments on mice were performed to validate the expression of LCN6, MUC4, and TNFRSF13C on experimental HF mice. Altogether, these three candidate genes are promising targets for the prediction of HF with immunological perspective.
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Affiliation(s)
- Wanrong Wang
- Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China; Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China
| | - Jie Xia
- Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China
| | - Yu Shen
- Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China
| | - Chuncan Qiao
- Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China
| | - Mengyan Liu
- Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China
| | - Xin Cheng
- Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China
| | - Siqi Mu
- First Clinical Medical College, Anhui Medical University, Hefei, 230032, China
| | - Weizhen Yan
- Department of Oncology, Xiangya Hospital of Central South University, Changsha, 410008, China
| | - Wenjie Lu
- Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China.
| | - Shan Gao
- Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China.
| | - Kai Zhou
- Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China; The Second Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
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19
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Butta N, van der Wal DE. Desialylation by neuraminidases in platelets, kiss of death or bittersweet? Curr Opin Hematol 2025; 32:43-51. [PMID: 38529832 DOI: 10.1097/moh.0000000000000815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/27/2024]
Abstract
PURPOSE OF REVIEW Loss of surface sialic acid by neuraminidases is known as 'desialylation'. Platelets are desialylated in bacterial or viral infections, during storage, senescence, various mutations, platelet auto antibodies, hemostasis and shear stress. In this review the recent literature on the different sialic acid capped glycan structures will be covered as well as platelet desialylation in inherited glycan disorders and induced by external neuraminidases. RECENT FINDINGS Neuraminidases are released from platelet intracellular stores and translocated to the platelet surface. Apart from clearance, loss of surface sialic acid by neuraminidases ('desialylation') affects platelet signaling including ligand binding and their procoagulant function. Platelets are also desialylated in infections, various mutations, presence of platelet auto antibodies. SUMMARY Since platelet desialylation occurs in various healthy and pathological conditions, measuring desialylation might be a new diagnostic tool.
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Affiliation(s)
- Nora Butta
- Group of Coagulopathies and Haemostasis Disorders, La Paz University Hospital Research Institute (IdiPAZ), Madrid, Spain
| | - Dianne E van der Wal
- Platelets and Thrombosis Research Laboratory, Anzac Research Institute, Concord Repatriation General Hospital, Concord, New South Wales, Australia
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20
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Gipsman AI, Bhandari A, Bhandari V. Use of mucolytics and inhaled antibiotics in the NICU. J Perinatol 2025; 45:5-12. [PMID: 39562833 PMCID: PMC11711088 DOI: 10.1038/s41372-024-02178-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 11/05/2024] [Accepted: 11/08/2024] [Indexed: 11/21/2024]
Abstract
Clearance of airway secretions and treatment of respiratory tract infections (RTIs) are two common problems caregivers face in the neonatal intensive care unit (NICU). Mucolytics degrade crosslinks in mucus gel, reducing mucus viscosity and facilitating their removal by cough or endotracheal suctioning. While such medications have been studied in older children and adults, their use is not as well described in the NICU. For RTIs, systemic antibiotics are usually prescribed, although their use is often associated with adverse effects. Inhaled antibiotics may provide increased drug concentrations to the infected airways while minimizing systemic toxicity. The use of inhaled antibiotics in the NICU has been described in small case series. As underlying physiologic differences will lend to inaccuracies when extrapolating data obtained from older children, there is an urgent need to determine the safety, efficacy, and optimal dosing of inhaled mucolytics and antibiotics in infants of varying gestational and post-natal ages.
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Affiliation(s)
- Alexander I Gipsman
- Division of Pulmonary and Sleep Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Anita Bhandari
- Division of Pulmonary and Sleep Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Vineet Bhandari
- Division of Neonatology, The Children's Regional Hospital at Cooper, Camden, NJ, USA.
- Cooper Medical School of Rowan University, Camden, NJ, USA.
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21
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Kobayashi Y, Hanh CH, Yagi N, Le NKT, Yun Y, Shimamura A, Fukui K, Mitani A, Suzuki K, Kanda A, Iwai H. CCL4 Affects Eosinophil Survival via the Shedding of the MUC1 N-Terminal Domain in Airway Inflammation. Cells 2024; 14:33. [PMID: 39791734 PMCID: PMC11719767 DOI: 10.3390/cells14010033] [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: 11/22/2024] [Revised: 12/24/2024] [Accepted: 12/31/2024] [Indexed: 01/12/2025] Open
Abstract
Eosinophilic chronic rhinosinusitis (ECRS), a CRS with nasal polyps (CRSwNP), is characterized by eosinophilic infiltration with type 2 inflammation and is highly associated with bronchial asthma. Intractable ECRS with poorly controlled asthma is recognized as a difficult-to-treat eosinophilic airway inflammation. Although eosinophils are activated and coincubation with airway epithelial cells prolongs their survival, the interaction mechanism between eosinophils and epithelial cells is unclear. This study examined the effect of eosinophils on mucin glycoprotein 1 (MUC1), a member of membrane-bound mucin, in the airway epithelial cells, to elucidate the mechanisms of the eosinophil-airway epithelial cell interaction. Nasal polyp samples from patients with CRSwNP and BEAS-2B airway epithelial cells, coincubated with purified eosinophils, were stained with two MUC1 antibodies. To confirm the involvement of CCL4, an anti-CCL4 neutralizing antibody or recombinant CCL4 was used as needed. The immunofluorescence results revealed a negative correlation between the expression of full-length MUC1 and eosinophil count in nasal polyps. In BEAS-2B coincubated with eosinophils, full-length MUC1, but not the C-terminal domain, was reduced, and eosinophil survival was prolonged, which was concomitant with CCL4 increase, whereas the anti-CCL4 neutralizing antibody decreased these reactions. The survival of eosinophils that contacted recombinant MUC1 without the N-terminal domain was prolonged, and recombinant CCL4 increased the expression of metalloproteases. Increased CCL4 induces the contact between eosinophils and airway epithelial cells by shedding the MUC1 N-terminal domain and enhances eosinophil survival in eosinophilic airway inflammation. This novel mechanism may be a therapeutic target for difficult-to-treat eosinophilic airway inflammation.
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Affiliation(s)
- Yoshiki Kobayashi
- Airway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan; (C.H.H.); (N.K.T.L.); (Y.Y.); (A.S.); (K.F.); (A.M.); (K.S.); (A.K.); (H.I.)
- Allergy Center, Kansai Medical University Hospital, Osaka 573-1010, Japan
| | - Chu Hong Hanh
- Airway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan; (C.H.H.); (N.K.T.L.); (Y.Y.); (A.S.); (K.F.); (A.M.); (K.S.); (A.K.); (H.I.)
| | - Naoto Yagi
- Third Department of Internal Medicine, Kansai Medical University, Osaka 573-1010, Japan;
| | - Nhi Kieu Thi Le
- Airway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan; (C.H.H.); (N.K.T.L.); (Y.Y.); (A.S.); (K.F.); (A.M.); (K.S.); (A.K.); (H.I.)
| | - Yasutaka Yun
- Airway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan; (C.H.H.); (N.K.T.L.); (Y.Y.); (A.S.); (K.F.); (A.M.); (K.S.); (A.K.); (H.I.)
- Allergy Center, Kansai Medical University Hospital, Osaka 573-1010, Japan
| | - Akihiro Shimamura
- Airway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan; (C.H.H.); (N.K.T.L.); (Y.Y.); (A.S.); (K.F.); (A.M.); (K.S.); (A.K.); (H.I.)
| | - Kenta Fukui
- Airway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan; (C.H.H.); (N.K.T.L.); (Y.Y.); (A.S.); (K.F.); (A.M.); (K.S.); (A.K.); (H.I.)
| | - Akitoshi Mitani
- Airway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan; (C.H.H.); (N.K.T.L.); (Y.Y.); (A.S.); (K.F.); (A.M.); (K.S.); (A.K.); (H.I.)
| | - Kensuke Suzuki
- Airway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan; (C.H.H.); (N.K.T.L.); (Y.Y.); (A.S.); (K.F.); (A.M.); (K.S.); (A.K.); (H.I.)
| | - Akira Kanda
- Airway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan; (C.H.H.); (N.K.T.L.); (Y.Y.); (A.S.); (K.F.); (A.M.); (K.S.); (A.K.); (H.I.)
- Allergy Center, Kansai Medical University Hospital, Osaka 573-1010, Japan
| | - Hiroshi Iwai
- Airway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan; (C.H.H.); (N.K.T.L.); (Y.Y.); (A.S.); (K.F.); (A.M.); (K.S.); (A.K.); (H.I.)
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22
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Barbet K, Schmitz MS, Westhölter D, Kamler M, Rütten S, Thiebes AL, Sitek B, Bayer M, Schedel M, Reuter S, Darwiche K, Luengen AE, Taube C. Bronchoscopic biopsies - a novel source for primary airway epithelial cells in respiratory research. Respir Res 2024; 25:439. [PMID: 39719562 PMCID: PMC11669235 DOI: 10.1186/s12931-024-03060-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 11/29/2024] [Indexed: 12/26/2024] Open
Abstract
BACKGROUND Using primary airway epithelial cells (AEC) is essential to mimic more closely different types and stages of lung disease in humans while reducing or even replacing animal experiments. Access to lung tissue remains limited because these samples are generally obtained from patients who undergo lung transplantation for end-stage lung disease or thoracic surgery for (mostly) lung cancer. We investigated whether forceps or cryo biopsies are a viable alternative source of AEC compared to the conventional technique. METHODS AECs were obtained ex vivo from healthy donor lung tissue using the conventional method and two biopsy procedures (forceps, cryo). The influence of the isolation method on the quality and function of AEC was investigated at different time-points during expansion and differentiation in air-liquid interface cultures. In addition, fully-differentiated AECs were stimulated with house dust mite extract (HDM) to allow functional analyses in an allergic in vitro model. Vitality or differentiation capacity were determined using flow cytometry, scanning electron microscope, periodic acid-Schiff reaction, immunofluorescence staining, and proteomics. RESULTS As anticipated, no significant differences between each of the sampling methods were detected for any of the measured outcomes. The proteome composition was comparable for each isolation method, while donor-dependent effects were observed. Treatment with HDM led to minor differences in mucociliary differentiation. CONCLUSIONS Our findings confirmed the adequacy of these alternative approaches for attaining primary AECs, which can now expand the research for a broader range of lung diseases and for studies at an earlier stage not requiring lung surgery.
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Affiliation(s)
- Kimberly Barbet
- Department of Pulmonary Medicine, University Medical Center Essen, Ruhrlandklinik, Essen, Germany
| | - Mona S Schmitz
- Department of Pulmonary Medicine, University Medical Center Essen, Ruhrlandklinik, Essen, Germany.
- Department of Translational Pulmonology, Department of Pulmonary Medicine, University Medical Center Essen, Ruhrlandklinik, Essen, Germany.
| | - Dirk Westhölter
- Department of Pulmonary Medicine, University Medical Center Essen, Ruhrlandklinik, Essen, Germany
| | - Markus Kamler
- Department of Thoracic and Cardiovascular Surgery, University Medical Center Essen, Essen, Germany
| | - Stephan Rütten
- Institute of Pathology, Electron Microscopy Facility, RWTH Aachen University Hospital, Aachen, Germany
| | - Anja L Thiebes
- Department of Biohybrid and Medical Textiles (BioTex), AME - Institute of Applied Medical Engineering, Helmholtz Institute, RWTH Aachen University, Aachen, Germany
| | - Barbara Sitek
- Medical Proteom-Center (MPC) Medical Faculty, Ruhr-University Bochum, Bochum, Germany
- Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Knappschaftskrankenhaus, Bochum, Germany
| | - Malte Bayer
- Medical Proteom-Center (MPC) Medical Faculty, Ruhr-University Bochum, Bochum, Germany
- Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Knappschaftskrankenhaus, Bochum, Germany
| | - Michaela Schedel
- Department of Pulmonary Medicine, University Medical Center Essen, Ruhrlandklinik, Essen, Germany
- Department of Pulmonology, University Medical Center Essen, Essen, Germany
| | - Sebastian Reuter
- Department of Pulmonary Medicine, University Medical Center Essen, Ruhrlandklinik, Essen, Germany
- Present address: Basic and Translational Lung Research, Departments of Pneumology, Mainz University Medical Center, Mainz, Germany
| | - Kaid Darwiche
- Interventional Pulmonology, Department of Pulmonary Medicine, University Medical Center Essen, Ruhrlandklinik, Essen, Germany
| | - Anja E Luengen
- Department of Pulmonary Medicine, University Medical Center Essen, Ruhrlandklinik, Essen, Germany
| | - Christian Taube
- Department of Pulmonary Medicine, University Medical Center Essen, Ruhrlandklinik, Essen, Germany
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23
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Pincikova T, Merikallio H, Kotortsi I, Karimi R, Li CX, Lappi-Blanco E, Lindén SK, Padra M, Wheelock ÅM, Nyrén S, Sköld CM, Kaarteenaho RL. Expression Levels of MUC5AC and MUC5B in Airway Goblet Cells Are Associated with Traits of COPD and Progression of Chronic Airflow Limitation. Int J Mol Sci 2024; 25:13653. [PMID: 39769414 PMCID: PMC11678853 DOI: 10.3390/ijms252413653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 12/11/2024] [Accepted: 12/16/2024] [Indexed: 01/11/2025] Open
Abstract
Mucins 5AC (MUC5AC) and 5B (MUC5B) are the major mucins providing the organizing framework for the airway's mucus gel. We retrieved bronchial mucosal biopsies and bronchial wash (BW) samples through bronchoscopy from patients with chronic obstructive pulmonary disease (n = 38), healthy never-smokers (n = 40), and smokers with normal lung function (n = 40). The expression of MUC5AC and MUC5B was assessed immunohistochemically. The mucin concentrations in BW were determined using the slot-blot technique. The immunohistochemical expression of MUC5AC and MUC5B was localized to goblet cells and submucosal glands. Smokers had higher MUC5AC and lower MUC5B goblet cell expression and higher concentrations of soluble MUC5AC in BW than never-smokers. The MUC5B expression in goblet cells correlated positively with expiratory air flows, diffusing capacity, and the dyspnoea score. Chronic bronchitis, emphysema, and the progression of chronic airflow limitation during a median follow-up time of 8.4 years were associated with higher MUC5AC and lower MUC5B expression in goblet cells. Sustainers, slow progressors, and rapid progressors of airflow obstruction differed in their MUC5B expression at baseline. Emphysema and bronchial wall thickening on CT at a follow-up visit were associated with lower MUC5B expression at baseline. Our findings strengthen the hypothesis that MUC5AC and MUC5B are yet another contributing factor to smoking-associated lung disease progression.
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Grants
- NA The Foundation of the Finnish Anti-Tuberculosis Association
- NA The Jalmari and Rauha Ahokas Foundation
- NA The Research Foundation of the Pulmonary Diseases
- NA A state subsidy of Oulu University Hospital
- CMS 20100435, 20130293, 20160418, 20180235, 20190320; SL 20230626 The Swedish Heart-Lung Foundation
- CMS 2016 The Swedish Respiratory Society
- CMS 2011, 2012, 2013 King Gustaf V's and Queen Victoria's Freemasons' Foundation
- CMS 2010 Hesselmans Foundation
- NA Karolinska Institutet
- 2017-01142, 2018-00520 and 2021-02542 The Swedish Research Council
- CMS 071217 The Swedish Cancer- and Allergy Foundation
- CMS 2013 Sandoz A/S
- CMS 20110434, 20130051, 20150061, 20170393 and 20200287 The Regional Agreement on Medical Training and Clinical Research (ALF) between Stockholm County Council and Karolinska Institutet
- MCF [7214]-2013 ERS-EU RESPIRE2
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Affiliation(s)
- Terezia Pincikova
- Respiratory Medicine Unit, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institute, 171 76 Stockholm, Sweden (Å.M.W.)
- Stockholm CF-Center, Albatross, K56, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden
| | - Heta Merikallio
- Research Unit of Biomedicine and Internal Medicine, University of Oulu, 902 20 Oulu, Finland
- Center of Internal Medicine and Respiratory Medicine, Medical Research Center Oulu, Oulu University Hospital, 902 20 Oulu, Finland
| | - Ioanna Kotortsi
- Respiratory Medicine Unit, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institute, 171 76 Stockholm, Sweden (Å.M.W.)
- Department of Respiratory Medicine and Allergy, Karolinska University Hospital, 171 76 Stockholm, Sweden
| | - Reza Karimi
- Respiratory Medicine Unit, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institute, 171 76 Stockholm, Sweden (Å.M.W.)
| | - Chuan-Xing Li
- Respiratory Medicine Unit, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institute, 171 76 Stockholm, Sweden (Å.M.W.)
| | - Elisa Lappi-Blanco
- Cancer and Translational Medicine Research Unit, Department of Pathology, Oulu University Hospital and University of Oulu, 902 20 Oulu, Finland
| | - Sara K. Lindén
- Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden; (S.K.L.)
| | - Médea Padra
- Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden; (S.K.L.)
| | - Åsa M. Wheelock
- Respiratory Medicine Unit, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institute, 171 76 Stockholm, Sweden (Å.M.W.)
- Department of Respiratory Medicine and Allergy, Karolinska University Hospital, 171 76 Stockholm, Sweden
| | - Sven Nyrén
- Department of Molecular Medicine and Surgery, Division of Radiology, Karolinska Institute, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden
| | - Carl Magnus Sköld
- Respiratory Medicine Unit, Department of Medicine Solna and Center for Molecular Medicine, Karolinska Institute, 171 76 Stockholm, Sweden (Å.M.W.)
- Department of Respiratory Medicine and Allergy, Karolinska University Hospital, 171 76 Stockholm, Sweden
| | - Riitta L. Kaarteenaho
- Research Unit of Biomedicine and Internal Medicine, University of Oulu, 902 20 Oulu, Finland
- Center of Internal Medicine and Respiratory Medicine, Medical Research Center Oulu, Oulu University Hospital, 902 20 Oulu, Finland
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24
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Nakamura K, Baba R, Kokubu K, Harada M, Morimoto H. Alterations in Ileal Secretory Cells of The DSS-Induced Colitis Model Mice. Acta Histochem Cytochem 2024; 57:199-209. [PMID: 39776935 PMCID: PMC11703563 DOI: 10.1267/ahc.24-00049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 10/18/2024] [Indexed: 01/11/2025] Open
Abstract
Inflammatory bowel disease is triggered by abnormalities in epithelial barrier function and immunological responses, although its pathogenesis is poorly understood. The dextran sodium sulphate (DSS)-induced colitis model has been used to examine inflammation in the colon. Damage to mucosa primality occurs in the large intestine and scarcely in the small intestine. To evaluate the effect on the ileum, we histologically analyzed the inflammatory and recovery phases in DSS model mice, and 40 kDa FITC-dextran was used to investigate barrier function. In the inflammatory phase, histological damage was insignificant. However, expanded crypts, hypertrophic goblet and Paneth cells, increased mucus production and secretion were observed. The cellular morphology was restored to that of the control in the recovery phase. According to in situ hybridization and lectin histochemistry, the expression of intestinal stem cell markers, secretory cell differentiation factors, and glycosylation of secretory granules in Paneth cells differed in the DSS model. DSS-treatment did not influence the barrier function in the ileum, and FITC-dextran did not diffuse via the paracellular pathway into the mucosa. However, cells incorporating FITC appeared even under normal conditions. The number of FITC-positive Paneth cells was lower in the DSS group than the control group. Our results showed morphological and functional alterations in ileal epithelial cells, especially secretory cells, in the DSS colitis model.
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Affiliation(s)
- Kenta Nakamura
- Third Department of Internal Medicine, University of Occupational and Environmental Health, 1–1, Iseigaoka, Yahatanishi, Kitakyushu, Fukuoka 807–8555, Japan
- Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, 1–1, Iseigaoka, Yahatanishi, Kitakyushu, Fukuoka 807–8555, Japan
| | - Ryoko Baba
- Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, 1–1, Iseigaoka, Yahatanishi, Kitakyushu, Fukuoka 807–8555, Japan
| | - Keiji Kokubu
- Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, 1–1, Iseigaoka, Yahatanishi, Kitakyushu, Fukuoka 807–8555, Japan
| | - Masaru Harada
- Third Department of Internal Medicine, University of Occupational and Environmental Health, 1–1, Iseigaoka, Yahatanishi, Kitakyushu, Fukuoka 807–8555, Japan
| | - Hiroyuki Morimoto
- Department of Anatomy, School of Medicine, University of Occupational and Environmental Health, 1–1, Iseigaoka, Yahatanishi, Kitakyushu, Fukuoka 807–8555, Japan
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25
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Maloney Norcross SE, Levin LPK, Hickey AJ, Hill DB. Biopolymeric Inhalable Dry Powders for Pulmonary Drug Delivery. Pharmaceuticals (Basel) 2024; 17:1628. [PMID: 39770469 PMCID: PMC11728674 DOI: 10.3390/ph17121628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 11/25/2024] [Accepted: 11/28/2024] [Indexed: 01/16/2025] Open
Abstract
Natural and synthetic biopolymers are gaining popularity in the development of inhaled drug formulations. Their highly tunable properties and ability to sustain drug release allow for the incorporation of attributes not achieved in dry powder inhaler formulations composed only of micronized drugs, standard excipients, and/or carriers. There are multiple physiological barriers to the penetration of inhaled drugs to the epithelial surface, such as the periciliary layer mucus mesh, pulmonary macrophages, and inflammation and mucus compositional changes resulting from respiratory diseases. Biopolymers may facilitate transport to the epithelial surface despite such barriers. A variety of categories of biopolymers have been assessed for their potential in inhaled drug formulations throughout the research literature, ranging from natural biopolymers (e.g., chitosan, alginate, hyaluronic acid) to those synthesized in a laboratory setting (e.g., polycaprolactone, poly(lactic-co-glycolic acid)) with varying structures and compositions. To date, no biopolymers have been approved as a commercial dry powder inhaler product. However, advances may be possible in the treatment of respiratory diseases and infections upon further investigation and evaluation. Herein, this review will provide a thorough foundation of reported research utilizing biopolymers in dry powder inhaler formulations. Furthermore, insight and considerations for the future development of dry powder formulations will be proposed.
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Affiliation(s)
- Sara E. Maloney Norcross
- Technology Advancement and Commercialization, RTI International, Research Triangle Park, Durham, NC 27709, USA
| | - Leanna P. K. Levin
- Technology Advancement and Commercialization, RTI International, Research Triangle Park, Durham, NC 27709, USA
| | - Anthony J. Hickey
- Technology Advancement and Commercialization, RTI International, Research Triangle Park, Durham, NC 27709, USA
| | - David B. Hill
- Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Marsico Lung Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Department of Physics and Astronomy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
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26
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Pak SW, Kim WI, Lee SJ, Park SH, Cho YK, Kim JS, Kim JC, Kim SH, Shin IS. TXNIP regulates pulmonary inflammation induced by Asian sand dust. Redox Biol 2024; 78:103421. [PMID: 39520910 PMCID: PMC11671764 DOI: 10.1016/j.redox.2024.103421] [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: 10/03/2024] [Revised: 11/04/2024] [Accepted: 11/05/2024] [Indexed: 11/16/2024] Open
Abstract
Asian sand dust (ASD), a seasonal dust storm originating from the deserts of China and Mongolia, affects Korea and Japan during the spring, carrying soil particles and a variety of biochemical components. Exposure to ASD has been associated with the onset and exacerbation of respiratory disorders, although the underlying mechanisms remain unclear. This study investigates ASD-induced pulmonary toxicity and its mechanistic pathways, focusing on the role of thioredoxin-interacting protein (TXNIP). Using TXNIP knock-out (KO) mice and adeno-associated virus (AAV)-mediated TXNIP overexpression transgenic mice, we explored how TXNIP modulates ASD-induced pulmonary inflammation. Mice were exposed to ASD via intranasal administration on days 1, 3, and 5 to induce inflammation. ASD exposure led to significant pulmonary inflammation, evidenced by increased inflammatory cell counts and elevated cytokine levels in bronchoalveolar lavage fluid, as well as heightened protein expression of the TXNIP/NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. TXNIP KO mice exhibited attenuated airway inflammation and downregulation of the NLRP3 inflammasome compared to wild-type controls, while AAV-mediated TXNIP overexpression mice showed exacerbated inflammatory responses, including elevated NLRP3 inflammasome expression, compared to AAV-GFP controls. These findings suggest that TXNIP is a key regulator of ASD-induced pulmonary inflammation.
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Affiliation(s)
- So-Won Pak
- College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 77 Yong-bong-ro, Buk-gu, Gwangju, 61186, Republic of Korea
| | - Woong-Il Kim
- College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 77 Yong-bong-ro, Buk-gu, Gwangju, 61186, Republic of Korea
| | - Se-Jin Lee
- College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 77 Yong-bong-ro, Buk-gu, Gwangju, 61186, Republic of Korea
| | - Sin-Hyang Park
- College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 77 Yong-bong-ro, Buk-gu, Gwangju, 61186, Republic of Korea
| | - Young-Kwon Cho
- College of Health Sciences, Cheongju University, 298 Daesung-ro, Sangdang-gu, Cheongju-si, Chungbuk, 28503, Republic of Korea
| | - Joong-Sun Kim
- College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 77 Yong-bong-ro, Buk-gu, Gwangju, 61186, Republic of Korea
| | - Jong-Choon Kim
- College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 77 Yong-bong-ro, Buk-gu, Gwangju, 61186, Republic of Korea
| | - Sung-Hwan Kim
- Jeonbuk Branch, Korea Institute of Toxicology (KIT), Jeongeup-si, Jeonbuk, 53212, Republic of Korea.
| | - In-Sik Shin
- College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 77 Yong-bong-ro, Buk-gu, Gwangju, 61186, Republic of Korea.
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27
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Aroche R, Gao G, Li Y, Zhang Y, Rodríguez R, Martínez Y, Li X. Effect of Anacardium occidentale Leaf Powder on Growth Performance, Diarrhea Incidence, Blood Biochemistry, and Intestinal Traits in Weaned Piglets. Animals (Basel) 2024; 14:3382. [PMID: 39682348 DOI: 10.3390/ani14233382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Revised: 11/16/2024] [Accepted: 11/19/2024] [Indexed: 12/18/2024] Open
Abstract
To evaluate the phytobiotic effect of Anacardium occidentale leaf powder (AOLP) on growth performance, diarrhea incidence, blood biochemistry, and intestinal traits, seventy-two weaned piglets were randomly distributed into four groups (six replicates/group and three pigs/replicate) for 28 days, receiving a control diet (T0) or being supplemented with 5 (T1), 10 (T2), or 15 (T3) g/kg of AOLP. The diets did not affect the growth performance (p > 0.05); however, the AOLP groups had a decreased diarrhea incidence and malondialdehyde concentration (p < 0.05; 28 days). However, the AOLP groups had increased immunoglobulins (G and M) and villus heights (p < 0.05) in the duodenum. Likewise, T3 improved the number of goblet cells in the villi and the whole intestine (p < 0.01), the Mucin2 area in the jejunum and ileum (p < 0.05), occludin gene expression in the jejunum (p < 0.01), and acetic and valeric acid production (p < 0.05). Microbial diversity at the genus level was not different (p > 0.05); however, T3 increased the abundance of the Lactobacillus genus. These findings suggest that dietary supplementation with AOLP improved intestinal health by increasing antioxidant, immune, anti-inflammatory, and antidiarrheal activity in the weaned piglets.
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Affiliation(s)
- Roisbel Aroche
- Key Laboratory of Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
- Department of Animal Husbandry, Faculty of Agricultural Sciences, University of Granma, Bayamo 85100, Cuba
| | - Ge Gao
- Key Laboratory of Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Yanpin Li
- Key Laboratory of Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | | | - Román Rodríguez
- Animal Production Study Center, Faculty of Agricultural Sciences, University of Granma, Bayamo 85100, Cuba
| | - Yordan Martínez
- Faculty of Veterinary Medicine, University of Fondwa, Léogâne 6210, Haiti
| | - Xilong Li
- Key Laboratory of Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
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28
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Luo H, Gong WY, Zhang YY, Liu YY, Chen Z, Feng XL, Jiao QB, Zhang XW. IRE1β evolves to be a guardian of respiratory and gastrointestinal mucosa. Heliyon 2024; 10:e39011. [PMID: 39524875 PMCID: PMC11550042 DOI: 10.1016/j.heliyon.2024.e39011] [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: 06/25/2024] [Revised: 09/20/2024] [Accepted: 10/04/2024] [Indexed: 10/31/2024] Open
Abstract
Inositol-requiring enzyme 1 (IRE1), a mediator of the unfolded protein response, shows the highest degree of evolutionary conservation. Vertebrates express two IRE1 paralogs: IRE1α, which is universally expressed and IRE1β, which shows specific expression within mucus secreted cells in respiratory and gastrointestinal tracts. The biological properties and regulation of the two IRE1 duplicates show evolutionary differences. As recently suggested, IRE1β-deficient mice display impairment in secreted protein expression and mucosal homeostasis. Abnormal changes in IRE1β caused by external and internal factors can disrupt mucosal homeostasis and further lead to respiratory and gastrointestinal diseases. Here, we highlight the physiological functions of IRE1β in the respiratory and gastrointestinal tracts in response to environmental microbes, viruses, toxins, and food components.
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Affiliation(s)
- Hui Luo
- School of Clinical Medicine, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, 311121, China
| | - Wen-Yan Gong
- School of Clinical Medicine, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, 311121, China
| | - Yuan-Yuan Zhang
- Department of Cardiovascular Ultrasonic Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Ying-Ying Liu
- School of Clinical Medicine, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, 311121, China
| | - Zhen Chen
- School of Clinical Medicine, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, 311121, China
| | - Xing-Lin Feng
- School of Clinical Medicine, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, 311121, China
| | - Qi-Bin Jiao
- School of Clinical Medicine, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, 311121, China
| | - Xing-Wei Zhang
- School of Clinical Medicine, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, 311121, China
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Zhao R, Jiang C, Yuan Y, Zhang S, Ghonaim AH, Che C, Li X, Jin M, Jin E, Zeng X, Li S, Ren M. Isoleucine Enhanced the Function of the Small Intestinal Mucosal Barrier in Weaned Piglets to Alleviate Rotavirus Infection. Animals (Basel) 2024; 14:3146. [PMID: 39518871 PMCID: PMC11545378 DOI: 10.3390/ani14213146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 10/20/2024] [Accepted: 10/21/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Rotavirus (RV) is a major cause of diarrhea in young children and animals, especially piglets, leading to substantial economic losses in the global pig industry. Isoleucine (Ile), a branched-chain amino acid, plays an important role in regulating nutrient metabolism and has been shown to improve diarrhea. This study aimed to evaluate the effects of Ile supplementation on the mucosal immune barrier of the small intestine in RV-infected weaned piglets. METHODS Forty-eight 21-day-old weaned piglets were randomly divided into three dietary treatments (each treatment was subdivided into two groups, eight replicates per group), with 0%, 0.5%, or 1% Ile added for 15 days, and then, one group from each treatment was challenged with RV. RESULTS The results showed that 1% Ile added to the diet promoted the healthy development of the intestinal mucosa. Ile could restore the reduced villus height in the ileum and the goblet cell number in the duodenum and ileum to normal levels, improving the intestinal epithelial tight junctions in RV-infected piglets. Additionally, Ile increased the activity of lipase, amylase, and sucrase, as well as superoxide dismutase (SOD) and glutathione (GSH), along with the expression of SIgA, DEFβ1, and DEFβ2 in parts of the small intestine. CONCLUSIONS The addition of Ile to the diet mitigated the effects of RV infection on intestinal morphology and mucosal barrier function, as well as the physiological functions of weaned piglets, and improved the antioxidant and immune functions of the piglets to some extent. These findings offer valuable insights, contributing to a deeper understanding of the role of Ile in supporting intestinal health.
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Affiliation(s)
- Rongkun Zhao
- Anhui Provincial Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China; (R.Z.); (C.J.); (Y.Y.); (S.Z.); (C.C.); (X.L.); (M.J.); (E.J.)
| | - Changsheng Jiang
- Anhui Provincial Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China; (R.Z.); (C.J.); (Y.Y.); (S.Z.); (C.C.); (X.L.); (M.J.); (E.J.)
| | - Yuchen Yuan
- Anhui Provincial Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China; (R.Z.); (C.J.); (Y.Y.); (S.Z.); (C.C.); (X.L.); (M.J.); (E.J.)
| | - Shen Zhang
- Anhui Provincial Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China; (R.Z.); (C.J.); (Y.Y.); (S.Z.); (C.C.); (X.L.); (M.J.); (E.J.)
| | - Ahmed H. Ghonaim
- National Key Laboratory of Agricultural Microbiology, College of Animal Sciences and Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China;
- Desert Research Center, Cairo 11435, Egypt
| | - Chuanyan Che
- Anhui Provincial Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China; (R.Z.); (C.J.); (Y.Y.); (S.Z.); (C.C.); (X.L.); (M.J.); (E.J.)
| | - Xiaojin Li
- Anhui Provincial Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China; (R.Z.); (C.J.); (Y.Y.); (S.Z.); (C.C.); (X.L.); (M.J.); (E.J.)
| | - Mengmeng Jin
- Anhui Provincial Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China; (R.Z.); (C.J.); (Y.Y.); (S.Z.); (C.C.); (X.L.); (M.J.); (E.J.)
| | - Erhui Jin
- Anhui Provincial Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China; (R.Z.); (C.J.); (Y.Y.); (S.Z.); (C.C.); (X.L.); (M.J.); (E.J.)
| | - Xiangfang Zeng
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China;
| | - Shenghe Li
- Anhui Provincial Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China; (R.Z.); (C.J.); (Y.Y.); (S.Z.); (C.C.); (X.L.); (M.J.); (E.J.)
| | - Man Ren
- Anhui Provincial Key Laboratory of Animal Nutritional Regulation and Health, College of Animal Science, Anhui Science and Technology University, Fengyang 233100, China; (R.Z.); (C.J.); (Y.Y.); (S.Z.); (C.C.); (X.L.); (M.J.); (E.J.)
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Murphree-Terry M, Keith JD, Oden AM, Birket SE. Normalization of Muc5b ameliorates airway mucus plugging during persistent Pseudomonas aeruginosa infection in the CFTR -/- rat. Am J Physiol Lung Cell Mol Physiol 2024; 327:L672-L683. [PMID: 39316674 PMCID: PMC11563644 DOI: 10.1152/ajplung.00381.2023] [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: 12/04/2023] [Revised: 07/19/2024] [Accepted: 09/02/2024] [Indexed: 09/26/2024] Open
Abstract
In cystic fibrosis, the airway gel-forming mucin MUC5B accumulates in the airways, preventing clearance of pathogens like Pseudomonas aeruginosa (PA). The cystic fibrosis transmembrane conductance regulator (CFTR)-/- (KO) rat model exhibits a similar accumulation of Muc5b. Our lab has shown that increased Muc5b precipitates the development of chronic PA infection. We hypothesized that reducing Muc5b in the KO rat airway would prevent occlusive mucus plugs and development of persistent PA infection. Six-month-old KO rats received Muc5b or scramble siRNA via intratracheal instillation. Rats were then inoculated with 106 colony-forming units of mucoid P. aeruginosa isolate PAM57-15 and euthanized at 3- or 14-days post infection (dpi) to assess acute and persistent infection. At 14 dpi, Muc5b siRNA-treated KO rats had increased weight, decreased neutrophilic inflammation, and reduced mucus plugging in the small airways compared with scramble-treated KO and WT rats. These results indicate that pharmacological intervention of Muc5b reduces mucus plugging during persistent PA infection.NEW & NOTEWORTHY Although highly effective modulator therapies for cystic fibrosis (CF) have improved mucus-related outcomes of disease for people with CF, eradication of Pseudomonas aeruginosa (PA) infection has not been achieved in this population. In addition, current therapies for CF do not target mucin hypersecretion directly. Here, we show that a novel approach of normalizing airway Muc5b hypersecretion ameliorates infection-induced mucus plugging and neutrophilic inflammation during persistent PA infection in CFTR-/- rats.
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Affiliation(s)
- Mikayla Murphree-Terry
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States
- Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States
| | - Johnathan D Keith
- Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States
| | - Ashley M Oden
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States
| | - Susan E Birket
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States
- Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, United States
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Yang Z, Liu Z, Zhang J, Li X, Zeng D, Mu C, Jiang J. Study on the complications after implantation of different types of metal stents in rabbit trachea. Int J Pediatr Otorhinolaryngol 2024; 186:112111. [PMID: 39341020 DOI: 10.1016/j.ijporl.2024.112111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 09/09/2024] [Accepted: 09/12/2024] [Indexed: 09/30/2024]
Abstract
OBJECTIVE To observe the complications and inflammatory responses caused by the different types of metal stents in the trachea of rabbits. METHOD 79 rabbits were randomly divided into 4 groups and were implanted with the customized nickel-titanium alloy metal stents(fully covered metal stent: group A, bare metal stent: group B, segmented covered metal stent: group C and control group: group D). The complications (tracheal deformation, granulation tissue hyperplasia, scar hyperplasia and secretion retention) of different types of metal stents were compared by observing the anatomical and pathological specimens of dead rabbits; And the expression of inflammatory factors of different types of metal stents were compared by detecting the tissue of tracheas of dead rabbits. RESULTS (1)There were significant differences in the above four complications among groups A, B and C(p < 0.01). The incidences of tracheal deformation, scar hyperplasia and secretion retention in group A were significantly higher than that in group B(p < 0.0167), however, the incidence of granulation tissue hyperplasia in group A was significantly lower than that in group B(p < 0.0167). The incidence of scar hyperplasia in group A was significantly lower than that in group C(p < 0.0167) and there were no significant differences in other complications between these two groups(p > 0.0167). The incidences of tracheal deformation, scar hyperplasia and secretion retention in group B were significantly lower than that in group C(p < 0.0167), however, the incidence of granulation tissue hyperplasia in group B was significantly higher than that in group C(p < 0.0167). (2)The concentration of IL-1β in group A was higher than that in group B (p < 0.05 and foldchange>1.2). CONCLUSION (1)There are significant differences in complications between the fully covered metal stent, bare metal stent and segmented covered metal stent; the incidences of complications between the segmented covered metal stent and fully covered metal stent are similar. (2)Changes in different inflammatory factors can be observed between the fully covered and bare metal stent.
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Affiliation(s)
- Zhenyu Yang
- The Fourth Affiliated Hospital of Soochow University, Department of Respiratory and Critical Care Medicine, Suzhou, 215000, China; The First Affiliated Hospital of Soochow University, Department of Respiratory and Critical Care Medicine, Suzhou, 215000, China
| | - Ziyi Liu
- The First Affiliated Hospital of Soochow University, Department of Respiratory and Critical Care Medicine, Suzhou, 215000, China
| | - Jie Zhang
- The First Affiliated Hospital of Soochow University, Department of Respiratory and Critical Care Medicine, Suzhou, 215000, China
| | - Xiaoxiao Li
- The First Affiliated Hospital of Soochow University, Department of Respiratory and Critical Care Medicine, Suzhou, 215000, China
| | - Daxiong Zeng
- The Fourth Affiliated Hospital of Soochow University, Department of Respiratory and Critical Care Medicine, Suzhou, 215000, China; The First Affiliated Hospital of Soochow University, Department of Respiratory and Critical Care Medicine, Suzhou, 215000, China
| | - Chuanyong Mu
- The First Affiliated Hospital of Soochow University, Department of Respiratory and Critical Care Medicine, Suzhou, 215000, China.
| | - Junhong Jiang
- The Fourth Affiliated Hospital of Soochow University, Department of Respiratory and Critical Care Medicine, Suzhou, 215000, China; The First Affiliated Hospital of Soochow University, Department of Respiratory and Critical Care Medicine, Suzhou, 215000, China.
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Ma J, Wu C, Xu J. The Development of Lung Tissue Engineering: From Biomaterials to Multicellular Systems. Adv Healthc Mater 2024; 13:e2401025. [PMID: 39206615 DOI: 10.1002/adhm.202401025] [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: 03/22/2024] [Revised: 07/29/2024] [Indexed: 09/04/2024]
Abstract
The challenge of the treatment of end-stage lung disease poses an urgent clinical demand for lung tissue engineering. Over the past few years, various lung tissue-engineered constructs are developed for lung tissue regeneration and respiratory pathology study. In this review, an overview of recent achievements in the field of lung tissue engineering is proposed. The introduction of lung structure and lung injury are stated briefly at first. After that, the lung tissue-engineered constructs are categorized into three types: acellular, monocellular, and multicellular systems. The different bioengineered constructs included in each system that can be applied to the reconstruction of the trachea, airway epithelium, alveoli, and even whole lung are described in detail, followed by the highlight of relevant representative research. Finally, the challenges and future directions of biomaterials, manufacturing technologies, and cells involved in lung tissue engineering are discussed. Overall, this review can provide referable ideas for the realization of functional lung regeneration and permanent lung substitution.
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Affiliation(s)
- Jingge Ma
- Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, P. R. China
- Institute of Respiratory Medicine, School of Medicine, Tongji University, Shanghai, 200433, P. R. China
| | - Chengtie Wu
- State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China
- Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China
| | - Jinfu Xu
- Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, P. R. China
- Institute of Respiratory Medicine, School of Medicine, Tongji University, Shanghai, 200433, P. R. China
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Liu S, Yin J, Wan D, Yin Y. The Role of Iron in Intestinal Mucus: Perspectives from Both the Host and Gut Microbiota. Adv Nutr 2024; 15:100307. [PMID: 39341502 PMCID: PMC11533511 DOI: 10.1016/j.advnut.2024.100307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Revised: 09/10/2024] [Accepted: 09/22/2024] [Indexed: 10/01/2024] Open
Abstract
Although research on the role of iron in host immunity has a history spanning decades, it is only relatively recently that attention has been directed toward the biological effects of iron on the intestinal mucus layer, prompted by an evolving understanding of the role of this material in immune defense. The mucus layer, secreted by intestinal goblet cells, covers the intestinal epithelium, and given its unique location, interactions between the host and gut microbiota, as well as among constituent microbiota, occur frequently within the mucus layer. Iron, as an essential nutrient for the vast majority of life forms, regulates immune responses from both the host and microbial perspectives. In this review, we summarize the iron metabolism of both the host and gut microbiota and describe how iron contributes to intestinal mucosal homeostasis via the intestinal mucus layer with respect to both host and constituent gut microbiota. The findings described herein offer a new perspective on iron-mediated intestinal mucosal barrier function.
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Affiliation(s)
- Shuan Liu
- Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China; University of Chinese Academy of Sciences, Beijing, China
| | - Jie Yin
- College of Animal Science and Technology, Hunan Agriculture University, Changsha, China
| | - Dan Wan
- Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China.
| | - Yulong Yin
- Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China; University of Chinese Academy of Sciences, Beijing, China.
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Rogliani P, Manzetti GM, Gholamalishahi S, Cazzola M, Calzetta L. Impact of N-Acetylcysteine on Mucus Hypersecretion in the Airways: A Systematic Review. Int J Chron Obstruct Pulmon Dis 2024; 19:2347-2360. [PMID: 39493366 PMCID: PMC11531296 DOI: 10.2147/copd.s474512] [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: 06/04/2024] [Accepted: 10/09/2024] [Indexed: 11/05/2024] Open
Abstract
Mucus clearance is crucial for airway protection, and its dysfunction leads to chronic obstructive pulmonary disease (COPD) characterized by mucus hypersecretion (MHS) and impaired clearance. MUC5AC and MUC5B mucin proteins are key components of airway mucus, with MUC5AC being particularly responsive to environmental stimuli, making it a potential COPD biomarker. N-acetylcysteine (NAC) is a mucolytic agent with known effects on mucus viscosity and clearance, but its precise mechanisms in COPD remain unclear. This systematic review evaluated the impact of NAC on MHS in the airways, reporting significant inhibitory effects on MUC5AC and MUC5B gene and protein expression, as well as a reduction in the number of goblet cells. NAC has demonstrated efficacy in vitro and in animal models of MHS, including COPD models, but data on human bronchial tissue are lacking. This systematic review suggests that NAC acts as a mucolytic and a mucoregulator, directly inhibiting mucus secretion and goblet cell hyperplasia. Given the critical role of MHS in COPD progression, exacerbations, and mortality, these findings highlight the potential of NAC as a targeted therapy for hypersecretion COPD phenotypes. However, further studies are needed to confirm the results of this systematic review, even in human bronchial tissue, to provide translatable evidence in clinical settings. Understanding the intimate mechanism of NAC versus MHS regulation may pave the way for more effective treatments targeting airway mucus dysfunction in COPD, ultimately improving patient outcomes and reducing morbidity and mortality associated with chronic mucus hypersecretion.
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Affiliation(s)
- Paola Rogliani
- Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy
| | - Gian Marco Manzetti
- Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy
| | - Shima Gholamalishahi
- Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy
| | - Mario Cazzola
- Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy
| | - Luigino Calzetta
- Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy
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Zhang P, Yang D, Xiao J, Hong W, Sun H, Xie Q, Zeng C. Artemisia argyi polysaccharide alleviates osmotic diarrhea by enhancing intestinal barrier protection and anti-inflammation. Int J Biol Macromol 2024; 282:136779. [PMID: 39442837 DOI: 10.1016/j.ijbiomac.2024.136779] [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: 04/08/2024] [Revised: 09/08/2024] [Accepted: 10/19/2024] [Indexed: 10/25/2024]
Abstract
Artemisia argyi polysaccharide (AAP) is a homogeneous polysaccharide with a molecular weight of 16 kDa, displaying anti-inflammatory, antioxidant, and anti-tumorigenic properties, and potential protective effects on intestinal barrier function. It is anticipated to serve as an efficient component in diarrhea treatment. This study aims to examine the impact of AAP on diarrhea severity, intestinal barrier function, and inflammation in diarrhea-induced rats. The results demonstrated that AAP treatment notably decreased the incidence of diarrhea, reduced its severity, and lowered the disease activity score in rats, while also increasing body weight. Oral administration of AAP augmented goblet cell counts and elevated mucin-2 expression, aiding in the restoration of the mucus barrier. Additionally, AAP treatment enhanced colonic microbial diversity by increasing the abundance of S24-7 and Lactobacillus, while decreasing the levels of Bacteroides, Clostridium, and Sutterella. Moreover, the AAP administration elevated the levels of steroid hormones, prostaglandins, and their derivatives. By inhibiting the TLR4/MyD88/NF-κB pathway, AAP mitigated the release of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and increased the secretion of anti-inflammatory factor (IL-10). Overall, oral AAP administration effectively combats osmotic diarrhea by fortifying mucus barrier integrity and exerting anti-inflammatory effects, suggesting its potential use as an adjunctive agent in oral rehydration therapy.
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Affiliation(s)
- Pengfei Zhang
- Department of Medical Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong 518110, China
| | - Dexin Yang
- Department of Medical Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong 518110, China
| | - Jiahai Xiao
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, Guangdong Medical University, Dongguan 523808, China
| | - Weitao Hong
- Department of Biochemistry and Molecular Biology, School of Basic Medicine, Guangdong Medical University, Dongguan 523808, China
| | - Huimin Sun
- Department of Medical Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong 518110, China
| | - Qingqing Xie
- Department of Medical Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong 518110, China
| | - Changchun Zeng
- Department of Medical Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong 518110, China; Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen 518110, China..
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Li C, Zhang X, Zhao L, Liu S. Multi-omics profiling reveals the molecular mechanisms of H 2O 2-induced detrimental effects on Thamnaconus septentrionalis. BMC Genomics 2024; 25:984. [PMID: 39434036 PMCID: PMC11492787 DOI: 10.1186/s12864-024-10903-0] [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: 07/14/2024] [Accepted: 10/15/2024] [Indexed: 10/23/2024] Open
Abstract
BACKGROUND Hydrogen peroxide (H2O2), a novel water treatment agent, can be used for disinfection, water quality adjustment, and disease prevention, while excessive H2O2 can injure farm animals, even leading to death. Hydrogen peroxide is a recommended disinfectant and bactericide for treating gill diseases and vibriosis in the greenfin horse-faced filefish Thamnaconus septentrionalis. However, its cumulative effect, toxic molecular mechanism and relevant signal transduction/metabolic networks in marine fishes are largely unknown. RESULTS We employed a multi-omics approach to investigate the detrimental effects of 50 mg/L H2O2 exposure (2 h/d) on filefish for 2 d, 4 d, and 6 d. Transcriptome sequencing showed that differentially expressed genes (DEGs) were mainly classified into functions such as signal transduction, nervous system, liver and bile acid metabolism, energy metabolism, cell adhesion and communication, inflammation and immune response. Metabolomic analysis found that the significantly changed metabolites (SCMs) were involved in phenylalanine metabolism, inflammatory mediator regulation, linoleic acid metabolism, and necroptosis. The main SCMs were cholic acid, carnitine C12:1, dimethylmalonic acid, glutamic acid, L-lactic acid, shikimic acid, 2-methylsuccinic acid, and others. Moreover, H2O2-induced oxidative stress also disturbs the balance of the gut microbiota, altering the microbial composition and affecting digestive processes. CONCLUSIONS Integrated multiomics analysis revealed that H2O2-induced detrimental impacts include mucosal damage, inflammatory and immune responses, altered energy metabolism, and gut microbiota disorders. These findings offer novel insights into the harmful effects and signal transduction/metabolic pathways triggered by H2O2 exposure in marine fishes.
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Affiliation(s)
- Chengcheng Li
- Observation and Research Station of Bohai Strait Eco-Corridor, Ministry of Natural Resources, First Institute of Oceanography, Qingdao, 266061, China
- Laboratory for Marine Ecology and Environmental Science, Qingdao Marine Science and Technology Center, Qingdao, 266237, China
| | - Xuanxuan Zhang
- School of Advanced Manufacturing, Fuzhou University, Jinjiang, China
| | - Linlin Zhao
- Observation and Research Station of Bohai Strait Eco-Corridor, Ministry of Natural Resources, First Institute of Oceanography, Qingdao, 266061, China.
- Laboratory for Marine Ecology and Environmental Science, Qingdao Marine Science and Technology Center, Qingdao, 266237, China.
- School of Advanced Manufacturing, Fuzhou University, Jinjiang, China.
| | - Shenghao Liu
- Observation and Research Station of Bohai Strait Eco-Corridor, Ministry of Natural Resources, First Institute of Oceanography, Qingdao, 266061, China.
- Laboratory for Marine Ecology and Environmental Science, Qingdao Marine Science and Technology Center, Qingdao, 266237, China.
- School of Advanced Manufacturing, Fuzhou University, Jinjiang, China.
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Peng Q, Zheng H, Quan L, Li S, Huang J, Li J, Xie G. Therapeutic Potential of Foodborne Indole Derived from Chinese Stinky Tofu in Reducing Intestinal Inflammation and Enhancing Barrier Function to Mitigate Alcoholic Liver Injury. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:21829-21842. [PMID: 39300777 DOI: 10.1021/acs.jafc.4c06203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/22/2024]
Abstract
Indole, a compound in Chinese stinky tofu (ST), acts as a ligand for the aryl hydrocarbon receptor (AHR). Despite extensive research on prebiotic compounds, indole's specific role in ST remains unexplored. This study used an ethanol gavage method to create an ALD (alcoholic liver disease) mouse model and investigate dietary indole's effects on the intestinal barrier. Our findings indicate that after 6 weeks of being fed ST, the indole present (2 mg/day) robustly activated the intestinal AHR, upregulating its target gene, CYP1A1 (cytochrome P450 1A1 enzyme). This activation significantly reduced intestinal permeability, mitigated alcohol-induced oxidative stress and inflammation, and restored intestinal barrier function. Consequently, the study demonstrates that foodborne indole substantially reduces alcohol absorption and lowers the expression levels of liver inflammation-related factors, thereby slowing the progression of ALD. These results highlight indole's therapeutic potential for treating ALD and its role in developing functional foods.
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Affiliation(s)
- Qi Peng
- National Engineering Research Center for Chinese CRW (branch center), School of Life and Environmental Sciences, Shaoxing University, Shaoxing 312000, Zhejiang, China
| | - Huajun Zheng
- National Engineering Research Center for Chinese CRW (branch center), School of Life and Environmental Sciences, Shaoxing University, Shaoxing 312000, Zhejiang, China
| | - Leping Quan
- National Engineering Research Center for Chinese CRW (branch center), School of Life and Environmental Sciences, Shaoxing University, Shaoxing 312000, Zhejiang, China
| | - Shanshan Li
- National Engineering Research Center for Chinese CRW (branch center), School of Life and Environmental Sciences, Shaoxing University, Shaoxing 312000, Zhejiang, China
| | - Jiaxin Huang
- National Engineering Research Center for Chinese CRW (branch center), School of Life and Environmental Sciences, Shaoxing University, Shaoxing 312000, Zhejiang, China
| | - Jiachen Li
- National Engineering Research Center for Chinese CRW (branch center), School of Life and Environmental Sciences, Shaoxing University, Shaoxing 312000, Zhejiang, China
| | - Guangfa Xie
- Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province, College of Biology and Environmental Engineering, Zhejiang Shuren University, Hangzhou 310015, China
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Stewart CG, Hilkin BM, Gansemer ND, Adam RJ, Dick DW, Sunderland JJ, Stoltz DA, Zabner J, Abou Alaiwa MH. Mucociliary clearance is impaired in small airways of cystic fibrosis pigs. Am J Physiol Lung Cell Mol Physiol 2024; 327:L415-L422. [PMID: 39104314 PMCID: PMC11482522 DOI: 10.1152/ajplung.00010.2024] [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: 01/08/2024] [Revised: 07/10/2024] [Accepted: 07/23/2024] [Indexed: 08/07/2024] Open
Abstract
Cystic fibrosis (CF) is a genetic disorder characterized by recurrent airway infections, inflammation, impaired mucociliary clearance, and progressive decline in lung function. The disease may start in the small airways; however, this is difficult to prove due to the limited accessibility of the small airways with the current single-photon mucociliary clearance assay. Here, we developed a dynamic positron emission tomography assay with high spatial and temporal resolution. We tested that mucociliary clearance is abnormal in the small airways of newborn cystic fibrosis pigs. Clearance of [68Ga]-tagged macroaggregated albumin from small airways started immediately after delivery and continued for the duration of the study. Initial clearance was fast but slowed down a few minutes after delivery. Cystic fibrosis pigs' small airways cleared significantly less than non-CF pigs' small airways (non-CF 25.1 ± 3.1% vs. CF 14.6 ± 0.1%). Stimulation of the cystic fibrosis airways with the purinergic secretagogue uridine-5'-triphosphate (UTP) further impaired clearance (non-CF with UTP 20.9 ± 0.3% vs. CF with UTP 13.0 ± 1.8%). None of the cystic fibrosis pigs treated with UTP (n = 6) cleared more than 20% of the delivered dose. These data indicate that mucociliary clearance in the small airways is fast and can easily be missed if the assay is not sensitive enough. The data also indicate that mucociliary clearance is impaired in the small airways of cystic fibrosis pigs. This defect is exacerbated by stimulation of mucus secretions with purinergic agonists.NEW & NOTEWORTHY We developed a novel positron emission tomography scan assay with unprecedented temporal and spatial resolution to measure mucociliary clearance in the small airways. We proved a long-standing but unproven assertion that mucociliary clearance is inherently abnormal in the small airways of newborn cystic fibrosis piglets that are otherwise free of infection or inflammation. This technique can be easily extended to other airway diseases such as asthma, idiopathic pulmonary fibrosis, or chronic obstructive pulmonary disease.
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Grants
- HL136813 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
- K08 HL135433 NHLBI NIH HHS
- P30 CA086862 NCI NIH HHS
- R56 HL147073 NHLBI NIH HHS
- HL051670 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
- P01 HL091842 NHLBI NIH HHS
- R01 HL136813 NHLBI NIH HHS
- HL167025 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
- P01 HL051670 NHLBI NIH HHS
- P30 ES005605 NIEHS NIH HHS
- R01 HL167025 NHLBI NIH HHS
- HL135433 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
- ABOU20A0-KB Cystic Fibrosis Foundation (CFF)
- HL091842 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
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Affiliation(s)
- Carley G Stewart
- Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, United States
- Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States
| | - Brieanna M Hilkin
- Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States
| | - Nicholas D Gansemer
- Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States
| | - Ryan J Adam
- Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States
| | - David W Dick
- Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States
| | - John J Sunderland
- Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States
| | - David A Stoltz
- Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, United States
- Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States
- Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States
- Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States
| | - Joseph Zabner
- Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, United States
- Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States
| | - Mahmoud H Abou Alaiwa
- Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, United States
- Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States
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Wu X, Du F, Zhang A, Zhang G, Xu R, Du X. KDELR2 is necessary for chronic obstructive pulmonary disease airway Mucin5AC hypersecretion via an IRE1α/XBP-1s-dependent mechanism. J Cell Mol Med 2024; 28:e70125. [PMID: 39365189 PMCID: PMC11451269 DOI: 10.1111/jcmm.70125] [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: 11/02/2023] [Revised: 09/14/2024] [Accepted: 09/20/2024] [Indexed: 10/05/2024] Open
Abstract
Airway mucus hypersecretion, a crucial pathological feature of chronic obstructive pulmonary disease (COPD), contributes to the initiation, progression, and exacerbation of this disease. As a macromolecular mucin, the secretory behaviour of Mucin5AC (MUC5AC) is highly dependent on a series of modifying and folding processes that occur in the endoplasmic reticulum (ER). In this study, we focused on the ER quality control protein KDEL receptor (KDELR) and demonstrated that KDELR2 and MUC5AC were colocalized in the airway epithelium of COPD patients and COPD model rats. In addition, knockdown of KDELR2 markedly reduced the expression of MUC5AC both in vivo and in vitro and knockdown of ATF6 further decreased the levels of KDELR2. Furthermore, pretreatment with 4μ8C, an IRE1α inhibitor, led to a partial reduction in the expression of KDELR2 and MUC5AC both in vivo and in vitro, which indicated the involvement of IRE1α/XBP-1s in the upstream signalling cascade. Our study revealed that KDELR2 plays a crucial role in airway MUC5AC hypersecretion in COPD, which might be dependent on ATF6 and IRE1α/XBP-1s upstream signalling.
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Affiliation(s)
- Xiaojuan Wu
- Department of Respiratory and Critical Care MedicineThe Second Affiliated Hospital of Chongqing Medical UniversityChongqingChina
- Department of Respiratory and Critical Care MedicineSuining Central HospitalSuiningSichuanChina
| | - Fawang Du
- Department of Respiratory and Critical Care MedicineSuining Central HospitalSuiningSichuanChina
| | - Aijie Zhang
- Basic Laboratory, Key Laboratory of Metabolic DiseasesSuining Central HospitalSuiningChina
| | - Guoyue Zhang
- Department of Respiratory and Critical Care MedicineThe Second Affiliated Hospital of Chongqing Medical UniversityChongqingChina
| | - Rui Xu
- Department of Respiratory and Critical Care MedicineThe Second Affiliated Hospital of Chongqing Medical UniversityChongqingChina
| | - Xianzhi Du
- Department of Respiratory and Critical Care MedicineThe Second Affiliated Hospital of Chongqing Medical UniversityChongqingChina
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40
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Zhao Q, Gu M, Ni M, Li J, Wu T, Zhu S, Zhou Y, Lu Y, Li X, Xu H, Lu M. ROS responsive hydrogel for inhibition of MUC5AC against allergic rhinitis: A new delivery strategy for Ipratropium Bromide. Colloids Surf B Biointerfaces 2024; 242:114112. [PMID: 39047643 DOI: 10.1016/j.colsurfb.2024.114112] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 07/12/2024] [Accepted: 07/19/2024] [Indexed: 07/27/2024]
Abstract
Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa mediated by immunoglobulin E (IgE) after exposure to allergens. The bothersome symptoms of AR, such as runny nose and nasal congestion, affect millions of people worldwide. Ipratropium Bromide (IB), commonly used in clinical practice for treating AR, requires frequent administration through nasal spray and may cause significant irritation to the nasal mucosa. The induction of ROS is closely related to the initiation and symptoms of AR, and ROS will continue to accumulate during the onset of AR. To address these challenges, we have designed a drug delivery system that can be administered in liquid form and rapidly crosslink into a ROS-responsive gel in the nasal cavity. This system enables sustained ROS responsive release of IB in a high-concentration ROS environment at AR lesions, thereby alleviating AR symptoms. The gel demonstrated prolonged release of IB for up to 24 hours in rats. In the treatment of AR rat models, it improved their symptoms, reduced the expression of various inflammatory factors, suppressed MUC5AC protein expression, and decreased mucus secretion through a ROS responsive IB release pattern. Overall, this system holds promise as a better option for AR treatment and may inspire the design of nanogel-based nasal drug delivery systems.
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Affiliation(s)
- Qianqian Zhao
- Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Min Gu
- Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China
| | - Mengnan Ni
- Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Jinyu Li
- Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Ting Wu
- Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Senlin Zhu
- Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Yupeng Zhou
- Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Yawen Lu
- Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China
| | - Xiaolin Li
- Department of Geriatric Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210009, China.
| | - Huae Xu
- Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
| | - Meiping Lu
- Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
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41
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Calvigioni M, Mazzantini D, Celandroni F, Vozzi G, Ghelardi E. Cultivating complexity: Advancements in establishing in vitro models for the mucus-adhering gut microbiota. Microb Biotechnol 2024; 17:e70036. [PMID: 39435730 PMCID: PMC11494453 DOI: 10.1111/1751-7915.70036] [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: 05/15/2024] [Accepted: 10/02/2024] [Indexed: 10/23/2024] Open
Abstract
A healthy mucus is essential for maintaining intestinal homeostasis and overall well-being. In recent years, extensive research focused on understanding the intricate interactions between mucus and the gut microbiota. Mucus-adhering bacteria play crucial roles in preserving barrier integrity, epithelial permeability and mucus architecture, as well as in the colonization resistance against pathogens. Unravelling the significance of these microorganisms in human health and disease is challenging, primarily because most of the studies on the human gut microbiota rely on faecal samples, which do not fully represent the microecological complexity found in the intestinal mucosa. This review discusses novel strategies to specifically target and evaluate the mucosal microbiota, such as culturomics applied to mucosal biopsies or brushings, intestinal organoids and artificial in vitro models incorporating mucus.
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Affiliation(s)
- Marco Calvigioni
- Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of PisaPisaItaly
| | - Diletta Mazzantini
- Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of PisaPisaItaly
| | - Francesco Celandroni
- Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of PisaPisaItaly
| | - Giovanni Vozzi
- Department of Information BioengineeringUniversity of PisaPisaItaly
- Research Center Enrico PiaggioUniversity of PisaPisaItaly
| | - Emilia Ghelardi
- Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of PisaPisaItaly
- Research Center Nutraceuticals and Food for Health – NutrafoodUniversity of PisaPisaItaly
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42
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Tharavecharak S, Fujimoto H, Yasuma T, D’Alessandro-Gabazza CN, Toda M, Tomaru A, Saiki H, Uemura M, Kogue Y, Ito T, Furuhashi K, Okano T, Takeshita A, Nishihama K, Ono R, Hataji O, Nosaka T, Kobayashi T, Gabazza EC. Bleomycin-Induced Pulmonary Fibrosis in Transgenic Mice Carrying the Human MUC5B rs35705950 Variant. Cells 2024; 13:1523. [PMID: 39329706 PMCID: PMC11430646 DOI: 10.3390/cells13181523] [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: 07/27/2024] [Revised: 09/01/2024] [Accepted: 09/09/2024] [Indexed: 09/28/2024] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive, often fatal lung disease characterized by tissue scarring and declining lung function. The MUC5B promoter polymorphism rs35705950, a significant genetic predisposition for IPF, paradoxically associates with better survival and slower disease progression than other IPF genotypes. This study investigates the potential paradoxical protective effects of this MUC5B variant in lung fibrosis. For this purpose, we developed a transgenic mouse model overexpressing the human MUC5B rs35705950 variant in the proximal large airways. Lung fibrosis was induced through subcutaneous injection of bleomycin. Results demonstrated significantly reduced lung fibrosis severity in transgenic mice compared to wild-type mice, assessed by trichrome staining, Ashcroft scoring, and hydroxyproline levels. Additionally, transgenic mice showed significantly lower levels of inflammatory cells and cytokines (TNFα, IL-6, IFNγ) and growth factors (PDGF, CTGF, IL-13) in the bronchoalveolar lavage fluid and lung tissues. There was also a significant decrease in mRNA expressions of fibrosis-related markers (periostin, fibronectin, Col1a1). In summary, this study reveals that mucin overexpression related to the MUC5B rs35705950 variant in the large airways significantly attenuates lung fibrosis and inflammatory responses in transgenic mice. These findings suggest that the rs35705950 variant modulates inflammatory and fibrotic responses in the proximal airways, which may contribute to the slower disease progression observed in IPF patients carrying this variant. Our study offers a possible explanation for the paradoxical beneficial effects of the MUC5B variant despite its role as a significant predisposing factor for IPF.
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Affiliation(s)
- Suphachai Tharavecharak
- Department of Immunology, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
| | - Hajime Fujimoto
- Department Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
| | - Taro Yasuma
- Department of Immunology, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
- Microbiome Research Center, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
- Department of Diabetes, Endocrinology and Metabolism, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
| | - Corina N. D’Alessandro-Gabazza
- Department of Immunology, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
- Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana–Champaign, Urbana, IL 61801, USA
| | - Masaaki Toda
- Department of Immunology, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
| | - Atsushi Tomaru
- Department of Immunology, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
| | - Haruko Saiki
- Department of Immunology, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
| | - Mei Uemura
- Department of Diabetes, Endocrinology and Metabolism, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
| | - Yurie Kogue
- Department Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
| | - Toshiyuki Ito
- Department Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
| | - Kazuki Furuhashi
- Department Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
| | - Tomohito Okano
- Department Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
| | - Atsuro Takeshita
- Department of Immunology, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
- Department of Diabetes, Endocrinology and Metabolism, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
| | - Kota Nishihama
- Department of Diabetes, Endocrinology and Metabolism, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
| | - Ryoichi Ono
- Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu 514-8507, Mie, Japan
| | - Osamu Hataji
- Respiratory Center, Matsusaka Municipal Hospital, Tonomachi1550, Matsusaka 515-8544, Mie, Japan
| | - Tetsuya Nosaka
- Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu 514-8507, Mie, Japan
| | - Tetsu Kobayashi
- Department Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
- Microbiome Research Center, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
| | - Esteban C. Gabazza
- Department of Immunology, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
- Department Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
- Microbiome Research Center, Mie University, Edobashi 2-174, Tsu 514-8507, Mie, Japan
- Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana–Champaign, Urbana, IL 61801, USA
- Respiratory Center, Matsusaka Municipal Hospital, Tonomachi1550, Matsusaka 515-8544, Mie, Japan
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Paz C, Glassey A, Frick A, Sattar S, Zaorsky NG, Blitzer GC, Kimple RJ. Cancer therapy-related salivary dysfunction. J Clin Invest 2024; 134:e182661. [PMID: 39225092 PMCID: PMC11364403 DOI: 10.1172/jci182661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024] Open
Abstract
Salivary gland dysfunction is a common side effect of cancer treatments. Salivary function plays key roles in critical daily activities. Consequently, changes in salivary function can profoundly impair quality of life for cancer patients. We discuss salivary gland anatomy and physiology to understand how anticancer therapies such as chemotherapy, bone marrow transplantation, immunotherapy, and radiation therapy impair salivary function. We discuss approaches to quantify xerostomia in the clinic, including the advantages and limitations of validated quality-of-life instruments and approaches to directly measuring salivary function. Current and emerging approaches to treat cancer therapy-induced dry mouth are presented using radiation-induced salivary dysfunction as a model. Limitations of current sialagogues and salivary analogues are presented. Emerging approaches, including cellular and gene therapy and novel pharmacologic approaches, are described.
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Affiliation(s)
- Cristina Paz
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Annemarie Glassey
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Abigail Frick
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Sarah Sattar
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Nicholas G. Zaorsky
- University Hospitals Seidman Cancer Center, Cleveland, Ohio, USA
- Case Western Reserve University, Cleveland, Ohio, USA
| | - Grace C. Blitzer
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
- University of Wisconsin Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Randall J. Kimple
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
- University of Wisconsin Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
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44
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Ma DB, Zhang H, Wang XL, Wu QG. METTL3 aggravates cell damage induced by Streptococcus pneumoniae via the NEAT1/CTCF/MUC19 axis. Kaohsiung J Med Sci 2024; 40:722-731. [PMID: 38757482 DOI: 10.1002/kjm2.12843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 04/22/2024] [Accepted: 04/23/2024] [Indexed: 05/18/2024] Open
Abstract
Disruption of the alveolar barrier can trigger acute lung injury. This study elucidated the association of methyltransferase-like 3 (METTL3) with Streptococcus pneumoniae (SP)-induced apoptosis and inflammatory injury of alveolar epithelial cells (AECs). AECs were cultured and then infected with SP. Furthermore, the expression of METTL3, interleukin (IL)-10, IL-6, tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1), mucin 19 (MUC19), N6-methyladenosine (m6A), and NEAT1 after m6A modification were detected by qRT-PCR, Western blot, and enzyme-linked immunosorbent, m6A quantification, and methylated RNA immunoprecipitation-qPCR analyses, respectively. Moreover, the subcellular localization of NEAT1 was analyzed by nuclear/cytosol fractionation assay, and the binding between NEAT1 and CCCTC-binding factor (CTCF) was also analyzed. The results of this investigation revealed that SP-induced apoptosis and inflammatory injury in AECs and upregulated METTL3 expression. In addition, the downregulation of METTL3 alleviated apoptosis and inflammatory injury in AECs. METTL3-mediated m6A modification increased NEAT1 and promoted its binding with CTCF to facilitate MUC19 transcription. NEAT1 or MUC19 overexpression disrupted their protective role of silencing METTL3 in AECs, thereby increasing apoptosis and inflammatory injury. In conclusion, this is the first study to suggest that METTL3 aggravates SP-induced cell damage via the NEAT1/CTCF/MUC19 axis.
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Affiliation(s)
- Dong-Bo Ma
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, China
| | - Hui Zhang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, China
| | - Xi-Ling Wang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, China
| | - Qiu-Ge Wu
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, China
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45
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Reolon HG, Abduch NG, de Freitas AC, Silva RMDO, Fragomeni BDO, Lourenco D, Baldi F, de Paz CCP, Stafuzza NB. Proteomic changes of the bovine blood plasma in response to heat stress in a tropically adapted cattle breed. Front Genet 2024; 15:1392670. [PMID: 39149588 PMCID: PMC11324462 DOI: 10.3389/fgene.2024.1392670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 07/17/2024] [Indexed: 08/17/2024] Open
Abstract
Background Identifying molecular mechanisms responsible for the response to heat stress is essential to increase production, reproduction, health, and welfare. This study aimed to identify early biological responses and potential biomarkers involved in the response to heat stress and animal's recovery in tropically adapted beef cattle through proteomic analysis of blood plasma. Methods Blood samples were collected from 14 Caracu males during the heat stress peak (HSP) and 16 h after it (heat stress recovery-HSR) assessed based on wet bulb globe temperature index and rectal temperature. Proteome was investigated by liquid chromatography-tandem mass spectrometry from plasma samples, and the differentially regulated proteins were evaluated by functional enrichment analysis using DAVID tool. The protein-protein interaction network was evaluated by STRING tool. Results A total of 1,550 proteins were detected in both time points, of which 84 and 65 were downregulated and upregulated during HSR, respectively. Among the differentially regulated proteins with the highest absolute log-fold change values, those encoded by the GABBR1, EPHA2, DUSP5, MUC2, DGCR8, MAP2K7, ADRA1A, CXADR, TOPBP1, and NEB genes were highlighted as potential biomarkers because of their roles in response to heat stress. The functional enrichment analysis revealed that 65 Gene Ontology terms and 34 pathways were significant (P < 0.05). We highlighted those that could be associated with the response to heat stress, such as those related to the immune system, complement system, hemostasis, calcium, ECM-receptor interaction, and PI3K-Akt and MAPK signaling pathways. In addition, the protein-protein interaction network analysis revealed several complement and coagulation proteins and acute-phase proteins as important nodes based on their centrality and edges. Conclusion Identifying differentially regulated proteins and their relationship, as well as their roles in key pathways contribute to improve the knowledge of the mechanisms behind the response to heat stress in naturally adapted cattle breeds. In addition, proteins highlighted herein are potential biomarkers involved in the early response and recovery from heat stress in tropically adapted beef cattle.
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Affiliation(s)
| | - Natalya Gardezani Abduch
- Beef Cattle Research Center, Animal Science Institute, Sertãozinho, Brazil
- Department of Genetics, Ribeirao Preto Medical School (FMRP), University of Sao Paulo (USP), Ribeirão Preto, Brazil
| | - Ana Claudia de Freitas
- Beef Cattle Research Center, Animal Science Institute, Sertãozinho, Brazil
- Agricultural Research Agency of the State of Minas Gerais (EPAMIG), Patos de Minas, Brazil
| | | | | | - Daniela Lourenco
- Department of Animal and Dairy Science, University of Georgia, Athens, GA, United States
| | - Fernando Baldi
- Department of Animal Science, School of Agricultural and Veterinary Sciences, Sao Paulo State University (UNESP), Jaboticabal, Brazil
| | - Claudia Cristina Paro de Paz
- Department of Genetics, Ribeirao Preto Medical School (FMRP), University of Sao Paulo (USP), Ribeirão Preto, Brazil
- Sustainable Livestock Research Center, Animal Science Institute, São José do Rio Preto, Brazil
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46
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Zhang B, Yang Y, Li Q, Ding X, Tian M, Ma Q, Xu D. Impacts of PFOS, PFOA and their alternatives on the gut, intestinal barriers and gut-organ axis. CHEMOSPHERE 2024; 361:142461. [PMID: 38810808 DOI: 10.1016/j.chemosphere.2024.142461] [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: 12/20/2023] [Revised: 04/28/2024] [Accepted: 05/25/2024] [Indexed: 05/31/2024]
Abstract
With the restricted use of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), a number of alternatives to PFOS and PFOA have attracted great interest. Most of the alternatives are still characterized by persistence, bioaccumulation, and a variety of toxicity. Due to the production and use of these substances, they can be detected in the atmosphere, soil and water body. They affect human health through several exposure pathways and especially enter the gut by drinking water and eating food, which results in gut toxicity. In this review, we summarized the effects of PFOS, PFOA and 9 alternatives on pathological changes in the gut, the disruption of physical, chemical, biological and immune barriers of the intestine, and the gut-organ axis. This review provides a valuable understanding of the gut toxicity of PFOS, PFOA and their alternatives as well as the human health risks of emerging contaminants.
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Affiliation(s)
- Boxiang Zhang
- Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China
| | - Yunhui Yang
- Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China
| | - Qing Li
- Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China
| | - Xiaolin Ding
- Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China
| | - Mingming Tian
- Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China
| | - Qiao Ma
- Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China
| | - Dan Xu
- Institute of Environmental Systems Biology, Environment Science and Engineering College, Dalian Maritime University, Linghai Road 1, Dalian, 116026, PR China.
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47
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Cui C, Wang X, Zheng Y, Wu L, Li L, Wei H, Peng J. Nur77 as a novel regulator of Paneth cell differentiation and function. Mucosal Immunol 2024; 17:752-767. [PMID: 37683828 DOI: 10.1016/j.mucimm.2023.09.001] [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: 06/05/2023] [Revised: 08/11/2023] [Accepted: 09/01/2023] [Indexed: 09/10/2023]
Abstract
Serving as a part of intestinal innate immunity, Paneth cells play an important role in intestinal homeostasis maintenance via their multiple functions. However, the regulation of Paneth cells has been proven to be complex and diverse. Here, we identified nuclear receptor Nur77 as a novel regulator of Paneth cell differentiation and function. Nur77 deficiency led to the loss of Paneth cells in murine ileal crypts. Intestinal tissues or organoids with Nur77 deficiency exhibited the impaired intestinal stem cell niche and failed to enhance antimicrobial peptide expression after Paneth cell degranulation. The defects in Paneth cells and antimicrobial peptides in Nur7-/- mice led to intestinal microbiota disorders. Nur77 deficiency rendered postnatal mice susceptible to necrotizing enterocolitis. Mechanistically, Nur77 transcriptionally inhibited Dact1 expression to activate Wnt signaling activity, thus promoting Paneth cell differentiation and function. Taken together, our data suggest the regulatory role of Nur77 in Paneth cell differentiation and function and reveal a novel Dact1-mediated Wnt inhibition mechanism in Paneth cell development.
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Affiliation(s)
- Chenbin Cui
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan, China
| | - Xinru Wang
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan, China
| | - Yao Zheng
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan, China
| | - Lin Wu
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan, China
| | - Lindeng Li
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan, China
| | - Hongkui Wei
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan, China
| | - Jian Peng
- Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.
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48
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Zhu H, Leng J, Ju R, Qu S, Tian J, Leng H, Tao S, Liu C, Wu Z, Ren F, Lyu Y, Zhang N. Advantages of pulsed electric field ablation for COPD: Excellent killing effect on goblet cells. Bioelectrochemistry 2024; 158:108726. [PMID: 38733722 DOI: 10.1016/j.bioelechem.2024.108726] [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: 11/18/2023] [Revised: 05/03/2024] [Accepted: 05/06/2024] [Indexed: 05/13/2024]
Abstract
Mucus hypersecretion resulting from excessive proliferation and metaplasia of goblet cells in the airways is the pathological foundation for Chronic obstructive pulmonary disease (COPD). Clinical trials have confirmed the clinical efficacy of pulsed electric field ablation (PFA) for COPD, but its underlying mechanisms is poorly understood. Cellular and animal models of COPD (rich in goblet cells) were established in this study to detect goblet cells' sensitivity to PFA. Schwan's equation was adopted to calculate the cells' transmembrane potential and the electroporation areas in the cell membrane. We found that goblet cells are more sensitive to low-intensity PFA (250 V/cm-500 V/cm) than BEAS-2B cells. It is attributed to the larger size of goblet cells, which allows a stronger transmembrane potential formation under the same electric field strength. Additionally, the transmembrane potential of larger-sized cells can reach the cell membrane electroporation threshold in more areas. Trypan blue staining confirmed that the cells underwent IRE rate was higher in goblet cells than in BEAS-2B cells. Animal experiments also confirmed that the airway epithelium of COPD is more sensitive to PFA. We conclude that lower-intensity PFA can selectively kill goblet cells in the COPD airway epithelium, ultimately achieving the therapeutic effect of treating COPD.
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Affiliation(s)
- Haoyang Zhu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Department of Anesthesiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Jing Leng
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Ran Ju
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Shenao Qu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Jiawei Tian
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Haoze Leng
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Shiran Tao
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Chang Liu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Department of Anesthesiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Zheng Wu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Fenggang Ren
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yi Lyu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
| | - Nana Zhang
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
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49
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Salisbury SJ, Daniels RR, Monaghan SJ, Bron JE, Villamayor PR, Gervais O, Fast MD, Sveen L, Houston RD, Robinson N, Robledo D. Keratinocytes drive the epithelial hyperplasia key to sea lice resistance in coho salmon. BMC Biol 2024; 22:160. [PMID: 39075472 PMCID: PMC11287951 DOI: 10.1186/s12915-024-01952-8] [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: 11/15/2023] [Accepted: 06/28/2024] [Indexed: 07/31/2024] Open
Abstract
BACKGROUND Salmonid species have followed markedly divergent evolutionary trajectories in their interactions with sea lice. While sea lice parasitism poses significant economic, environmental, and animal welfare challenges for Atlantic salmon (Salmo salar) aquaculture, coho salmon (Oncorhynchus kisutch) exhibit near-complete resistance to sea lice, achieved through a potent epithelial hyperplasia response leading to rapid louse detachment. The molecular mechanisms underlying these divergent responses to sea lice are unknown. RESULTS We characterized the cellular and molecular responses of Atlantic salmon and coho salmon to sea lice using single-nuclei RNA sequencing. Juvenile fish were exposed to copepodid sea lice (Lepeophtheirus salmonis), and lice-attached pelvic fin and skin samples were collected 12 h, 24 h, 36 h, 48 h, and 60 h after exposure, along with control samples. Comparative analysis of control and treatment samples revealed an immune and wound-healing response that was common to both species, but attenuated in Atlantic salmon, potentially reflecting greater sea louse immunomodulation. Our results revealed unique but complementary roles of three layers of keratinocytes in the epithelial hyperplasia response leading to rapid sea lice rejection in coho salmon. Our results suggest that basal keratinocytes direct the expansion and mobility of intermediate and, especially, superficial keratinocytes, which eventually encapsulate the parasite. CONCLUSIONS Our results highlight the key role of keratinocytes in coho salmon's sea lice resistance and the diverged biological response of the two salmonid host species when interacting with this parasite. This study has identified key pathways and candidate genes that could be manipulated using various biotechnological solutions to improve Atlantic salmon sea lice resistance.
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Affiliation(s)
- S J Salisbury
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK.
| | - R Ruiz Daniels
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK
| | - S J Monaghan
- Institute of Aquaculture, University of Stirling, Stirling, UK
| | - J E Bron
- Institute of Aquaculture, University of Stirling, Stirling, UK
| | - P R Villamayor
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK
- Department of Genetics, University of Santiago de Compostela, Santiago de Compostela, Spain
| | - O Gervais
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK
| | - M D Fast
- Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Canada
| | | | - R D Houston
- Benchmark Genetics, 1 Pioneer BuildingMilton Bridge, Edinburgh TechnopolePenicuik, UK
| | - N Robinson
- Nofima AS, Tromsø, Norway.
- Sustainable Aquaculture Laboratory - Temperate and Tropical (SALTT), Deakin University, Melbourne, VIC, 3225, Australia.
| | - D Robledo
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK.
- Department of Genetics, University of Santiago de Compostela, Santiago de Compostela, Spain.
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50
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Zhu H, Zhou X, Ju R, Leng J, Tian J, Qu S, Tao S, Lyu Y, Zhang N. Challenges in clinical practice, biological mechanism and prospects of physical ablation therapy for COPD. Life Sci 2024; 349:122718. [PMID: 38754815 DOI: 10.1016/j.lfs.2024.122718] [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: 02/06/2024] [Revised: 05/03/2024] [Accepted: 05/11/2024] [Indexed: 05/18/2024]
Abstract
Chronic obstructive pulmonary disease (COPD) is projected to become the third leading cause of death globally by 2030. Despite the limited treatment options available for advanced COPD, which are mostly restricted to costly lung transplants, physical ablation therapy offers promising alternatives. This technique focuses on ablating lesioned airway epithelium, reducing secretions and obstructions, and promoting normal epithelial regeneration, demonstrating significant therapeutic potential. Physical ablation therapy primarily involves thermal steam ablation, cryoablation, targeted lung denervation, and high-voltage pulsed electric field ablation. These methods help transform the hypersecretory phenotype, alleviate airway inflammation, and decrease the volume of emphysematous lung segments by targeting goblet cells and damaged lung areas. Compared to traditional treatments, endoscopic physical ablation offers fewer injuries, quicker recovery, and enhanced safety. However, its application in COPD remains limited due to inconsistent clinical outcomes, a lack of well-understood mechanisms, and the absence of standardized guidelines. This review begins by exploring the development of these ablation techniques and their current clinical uses in COPD treatment. It then delves into the therapeutic effects reported in recent clinical studies and discusses the underlying mechanisms. Finally, the review assesses the future prospects and challenges of employing ablation technology in COPD clinical practice, aiming to provide a practical reference and a theoretical basis for its use and inspire further research.
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Affiliation(s)
- Haoyang Zhu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Department of Anesthesiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Xiaoyu Zhou
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Ran Ju
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Jing Leng
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Jiawei Tian
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shenao Qu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Shiran Tao
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China
| | - Yi Lyu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
| | - Nana Zhang
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
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