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      Environmental PM 2.5-triggered stress responses in digestive diseases

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      eGastroenterology

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          Abstract

          Airborne particulate matter in fine and ultrafine ranges (aerodynamic diameter less than 2.5 μm, PM 2.5) is a primary air pollutant that poses a serious threat to public health. Accumulating evidence has pointed to a close association between inhalation exposure to PM 2.5 and increased morbidity and mortality associated with modern human complex diseases. The adverse health effect of inhalation exposure to PM 2.5 pollutants is systemic, involving multiple organs, different cell types and various molecular mediators. Organelle damages and oxidative stress appear to play a major role in the cytotoxic effects of PM 2.5 by mediating stress response pathways related to inflammation, metabolic alteration and cell death programmes. The organs or tissues in the digestive tract, such as the liver, pancreas and small intestines, are susceptible to PM 2.5 exposure. This review underscores PM 2.5-induced inflammatory stress responses and their involvement in digestive diseases caused by PM 2.5 exposure.

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          Most cited references103

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          Inflammation and metabolic disorders.

          Metabolic and immune systems are among the most fundamental requirements for survival. Many metabolic and immune response pathways or nutrient- and pathogen-sensing systems have been evolutionarily conserved throughout species. As a result, immune response and metabolic regulation are highly integrated and the proper function of each is dependent on the other. This interface can be viewed as a central homeostatic mechanism, dysfunction of which can lead to a cluster of chronic metabolic disorders, particularly obesity, type 2 diabetes and cardiovascular disease. Collectively, these diseases constitute the greatest current threat to global human health and welfare.
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            The unfolded protein response: from stress pathway to homeostatic regulation.

            The vast majority of proteins that a cell secretes or displays on its surface first enter the endoplasmic reticulum (ER), where they fold and assemble. Only properly assembled proteins advance from the ER to the cell surface. To ascertain fidelity in protein folding, cells regulate the protein-folding capacity in the ER according to need. The ER responds to the burden of unfolded proteins in its lumen (ER stress) by activating intracellular signal transduction pathways, collectively termed the unfolded protein response (UPR). Together, at least three mechanistically distinct branches of the UPR regulate the expression of numerous genes that maintain homeostasis in the ER or induce apoptosis if ER stress remains unmitigated. Recent advances shed light on mechanistic complexities and on the role of the UPR in numerous diseases.
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              Signal integration in the endoplasmic reticulum unfolded protein response.

              The endoplasmic reticulum (ER) responds to the accumulation of unfolded proteins in its lumen (ER stress) by activating intracellular signal transduction pathways - cumulatively called the unfolded protein response (UPR). Together, at least three mechanistically distinct arms of the UPR regulate the expression of numerous genes that function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids and lipids. The arms of the UPR are integrated to provide a response that remodels the secretory apparatus and aligns cellular physiology to the demands imposed by ER stress.
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                Author and article information

                Journal
                9918664289006676
                52791
                eGastroenterology
                eGastroenterology
                eGastroenterology
                2766-0125
                2976-7296
                29 May 2024
                April 2024
                03 May 2024
                18 June 2024
                : 2
                : 2
                : e100063
                Affiliations
                Center for Molecular Medicine and Genetics, Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, Michigan, USA
                Author notes
                Correspondence to Dr Kezhong Zhang; kzhang@ 123456med.wayne.edu

                Contributors The author (KZ) conceived the idea and wrote the paper.

                Author information
                http://orcid.org/0000-0002-6062-235X
                Article
                NIHMS1995741
                10.1136/egastro-2024-100063
                11185827
                38895535
                4198b9f6-cdc2-4d9a-9eca-0ecc3642fa40

                Open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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