{"id":"https://openalex.org/W4409434697","doi":"https://doi.org/10.1016/j.lfs.2025.123634","title":"Roflumilast counteracts high-dose dexamethasone-induced steatohepatitis, metabolic abnormalities and aortic injury via inhibiting TNF-\u03b1/NF-\u03baB, NLRP3/IL-1\u03b2 and ER stress sensors","display_name":"Roflumilast counteracts high-dose dexamethasone-induced steatohepatitis, metabolic abnormalities and aortic injury via inhibiting TNF-\u03b1/NF-\u03baB, NLRP3/IL-1\u03b2 and ER stress sensors","publication_year":2025,"publication_date":"2025-04-14","ids":{"openalex":"https://openalex.org/W4409434697","doi":"https://doi.org/10.1016/j.lfs.2025.123634","pmid":"https://pubmed.ncbi.nlm.nih.gov/40233857"},"language":"en","primary_location":{"id":"doi:10.1016/j.lfs.2025.123634","doi":"https://doi.org/10.1016/j.lfs.2025.123634","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.lfs.2025.123634","pdf_url":null,"source":{"id":"https://openalex.org/S175775512","display_name":"Life Sciences","issn_l":"0024-3205","issn":["0024-3205","1879-0631"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-70","russia-white-list-1"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Life Sciences","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://doi.org/10.1016/j.lfs.2025.123634","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":null,"display_name":"Mohammed Fulayyih Aloufi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I159247623","display_name":"Mansoura University","ror":"https://ror.org/01k8vtd75","country_code":"EG","type":"education","lineage":["https://openalex.org/I159247623"]}],"countries":["EG"],"is_corresponding":false,"raw_author_name":"Mohammed Fulayyih Aloufi","raw_affiliation_strings":["Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt","Department of Pharmacology & Toxicology, , Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt","institution_ids":["https://openalex.org/I159247623"]},{"raw_affiliation_string":"Department of Pharmacology & Toxicology, , Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt","institution_ids":["https://openalex.org/I159247623"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5062099000","display_name":"Sara H. Hazem","orcid":"https://orcid.org/0000-0002-4421-3214","observed_orcids":["https://orcid.org/0000-0002-4421-3214"]},"institutions":[{"id":"https://openalex.org/I159247623","display_name":"Mansoura University","ror":"https://ror.org/01k8vtd75","country_code":"EG","type":"education","lineage":["https://openalex.org/I159247623"]}],"countries":["EG"],"is_corresponding":true,"raw_author_name":"Sara H. Hazem","raw_affiliation_strings":["Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: sarahesham12@mans.edu.eg","Department of Pharmacology & Toxicology, , Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: sarahesham12@mans.edu.eg"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: sarahesham12@mans.edu.eg","institution_ids":["https://openalex.org/I159247623"]},{"raw_affiliation_string":"Department of Pharmacology & Toxicology, , Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: sarahesham12@mans.edu.eg","institution_ids":["https://openalex.org/I159247623"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5040301978","display_name":"Rania Ramadan Abdelaziz","orcid":"https://orcid.org/0000-0002-6651-6187","observed_orcids":["https://orcid.org/0000-0002-6651-6187"]},"institutions":[{"id":"https://openalex.org/I159247623","display_name":"Mansoura University","ror":"https://ror.org/01k8vtd75","country_code":"EG","type":"education","lineage":["https://openalex.org/I159247623"]}],"countries":["EG"],"is_corresponding":false,"raw_author_name":"Rania R. Abdelaziz","raw_affiliation_strings":["Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt","Department of Pharmacology & Toxicology, , Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt","institution_ids":["https://openalex.org/I159247623"]},{"raw_affiliation_string":"Department of Pharmacology & Toxicology, , Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt","institution_ids":["https://openalex.org/I159247623"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5028677660","display_name":"Ghada Mohamed Suddek","orcid":"https://orcid.org/0000-0002-3283-9471","observed_orcids":["https://orcid.org/0000-0002-3283-9471"]},"institutions":[{"id":"https://openalex.org/I159247623","display_name":"Mansoura University","ror":"https://ror.org/01k8vtd75","country_code":"EG","type":"education","lineage":["https://openalex.org/I159247623"]}],"countries":["EG"],"is_corresponding":false,"raw_author_name":"Ghada M. Suddek","raw_affiliation_strings":["Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: ghmsuddek@mans.edu.eg","Department of Pharmacology & Toxicology, , Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: ghmsuddek@mans.edu.eg"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: ghmsuddek@mans.edu.eg","institution_ids":["https://openalex.org/I159247623"]},{"raw_affiliation_string":"Department of Pharmacology & Toxicology, , Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: ghmsuddek@mans.edu.eg","institution_ids":["https://openalex.org/I159247623"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5062099000"],"corresponding_institution_ids":["https://openalex.org/I159247623"],"apc_list":{"value":3810,"currency":"USD","value_usd":3810},"apc_paid":{"value":3810,"currency":"USD","value_usd":3810},"fwci":0.5051,"has_fulltext":false,"cited_by_count":2,"citation_normalized_percentile":{"value":0.55405405,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":90,"max":96},"biblio":{"volume":"372","issue":null,"first_page":"123634","last_page":"123634"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12434","display_name":"Phosphodiesterase function and regulation","score":0.4359999895095825,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T12434","display_name":"Phosphodiesterase function and regulation","score":0.4359999895095825,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11465","display_name":"Drug-Induced Hepatotoxicity and Protection","score":0.3068999946117401,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12421","display_name":"Adrenal Hormones and Disorders","score":0.0674000009894371,"subfield":{"id":"https://openalex.org/subfields/2712","display_name":"Endocrinology, Diabetes and Metabolism"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/roflumilast","display_name":"roflumilast","score":0.9980000257492065},{"id":"https://openalex.org/keywords/dexamethasone","display_name":"dexamethasone","score":0.949999988079071},{"id":"https://openalex.org/keywords/glucocorticoid-side-effects","display_name":"glucocorticoid adverse effects","score":0.9520000219345093},{"id":"https://openalex.org/keywords/steatohepatitis","display_name":"steatohepatitis","score":0.9309999942779541},{"id":"https://openalex.org/keywords/aortic-injury","display_name":"aortic injury","score":0.7820000052452087},{"id":"https://openalex.org/keywords/phosphodiesterase-4-inhibition","display_name":"phosphodiesterase 4 inhibition","score":0.8460000157356262},{"id":"https://openalex.org/keywords/tnf-alpha-nf-kappab-signaling","display_name":"TNF-\u03b1/NF-\u03baB signaling","score":0.871999979019165},{"id":"https://openalex.org/keywords/nlrp3-inflammasome","display_name":"NLRP3 inflammasome","score":0.9750000238418579},{"id":"https://openalex.org/keywords/interleukin-1beta","display_name":"IL-1\u03b2","score":0.9819999933242798},{"id":"https://openalex.org/keywords/endoplasmic-reticulum-stress","display_name":"endoplasmic reticulum stress","score":0.9800000190734863},{"id":"https://openalex.org/keywords/oxidative-stress","display_name":"oxidative stress","score":0.8759999871253967},{"id":"https://openalex.org/keywords/hepatoprotective-effect","display_name":"hepatoprotection","score":0.7839999794960022},{"id":"https://openalex.org/keywords/impaired-glucose-tolerance","display_name":"impaired glucose tolerance","score":0.7480000257492065},{"id":"https://openalex.org/keywords/insulin-resistance","display_name":"insulin resistance","score":0.8410000205039978},{"id":"https://openalex.org/keywords/camp-signaling","display_name":"cAMP signaling","score":0.5139999985694885},{"id":"https://openalex.org/keywords/glutathione","display_name":"glutathione","score":0.6140000224113464}],"concepts":[{"id":"https://openalex.org/C2780401358","wikidata":"https://www.wikidata.org/wiki/Q422252","display_name":"Dexamethasone","level":2,"score":0.6611900329589844},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.6563453674316406},{"id":"https://openalex.org/C2778926808","wikidata":"https://www.wikidata.org/wiki/Q693482","display_name":"Roflumilast","level":3,"score":0.6452078819274902},{"id":"https://openalex.org/C2779478299","wikidata":"https://www.wikidata.org/wiki/Q2335423","display_name":"Steatohepatitis","level":4,"score":0.5444558262825012},{"id":"https://openalex.org/C2776151105","wikidata":"https://www.wikidata.org/wiki/Q898814","display_name":"Oxidative stress","level":2,"score":0.5075701475143433},{"id":"https://openalex.org/C17991360","wikidata":"https://www.wikidata.org/wiki/Q21173843","display_name":"Tumor necrosis factor alpha","level":2,"score":0.5063062906265259},{"id":"https://openalex.org/C11988809","wikidata":"https://www.wikidata.org/wiki/Q412889","display_name":"Interleukin 6","level":3,"score":0.47882822155952454},{"id":"https://openalex.org/C2776914184","wikidata":"https://www.wikidata.org/wiki/Q101991","display_name":"Inflammation","level":2,"score":0.46837860345840454},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.46050259470939636},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.39766883850097656},{"id":"https://openalex.org/C2776780178","wikidata":"https://www.wikidata.org/wiki/Q199804","display_name":"COPD","level":2,"score":0.13401231169700623},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.12162834405899048},{"id":"https://openalex.org/C2778772119","wikidata":"https://www.wikidata.org/wiki/Q6058862","display_name":"Fatty liver","level":3,"score":0.12026050686836243}],"mesh":[{"descriptor_ui":"D000071199","descriptor_name":"NLR Family, Pyrin Domain-Containing 3 Protein","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D000071199","descriptor_name":"NLR Family, Pyrin Domain-Containing 3 Protein","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D000071199","descriptor_name":"NLR Family, Pyrin Domain-Containing 3 Protein","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D000071199","descriptor_name":"NLR Family, Pyrin Domain-Containing 3 Protein","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000071199","descriptor_name":"NLR Family, Pyrin Domain-Containing 3 Protein","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000071199","descriptor_name":"NLR Family, Pyrin Domain-Containing 3 Protein","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000631","descriptor_name":"Aminopyridines","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D000631","descriptor_name":"Aminopyridines","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D000631","descriptor_name":"Aminopyridines","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001011","descriptor_name":"Aorta","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D001011","descriptor_name":"Aorta","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D001011","descriptor_name":"Aorta","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D001011","descriptor_name":"Aorta","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D001011","descriptor_name":"Aorta","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D001011","descriptor_name":"Aorta","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D001018","descriptor_name":"Aortic Diseases","qualifier_ui":"Q000139","qualifier_name":"chemically induced","is_major_topic":true},{"descriptor_ui":"D001018","descriptor_name":"Aortic Diseases","qualifier_ui":"Q000139","qualifier_name":"chemically induced","is_major_topic":true},{"descriptor_ui":"D001018","descriptor_name":"Aortic Diseases","qualifier_ui":"Q000139","qualifier_name":"chemically induced","is_major_topic":true},{"descriptor_ui":"D001018","descriptor_name":"Aortic Diseases","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D001018","descriptor_name":"Aortic Diseases","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D001018","descriptor_name":"Aortic Diseases","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D001018","descriptor_name":"Aortic Diseases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D001018","descriptor_name":"Aortic Diseases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D001018","descriptor_name":"Aortic Diseases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D001549","descriptor_name":"Benzamides","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D001549","descriptor_name":"Benzamides","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D001549","descriptor_name":"Benzamides","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D003521","descriptor_name":"Cyclopropanes","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D003521","descriptor_name":"Cyclopropanes","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D003521","descriptor_name":"Cyclopropanes","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D003907","descriptor_name":"Dexamethasone","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":true},{"descriptor_ui":"D003907","descriptor_name":"Dexamethasone","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":true},{"descriptor_ui":"D003907","descriptor_name":"Dexamethasone","qualifier_ui":"Q000009","qualifier_name":"adverse effects","is_major_topic":true},{"descriptor_ui":"D003907","descriptor_name":"Dexamethasone","qualifier_ui":"Q000633","qualifier_name":"toxicity","is_major_topic":true},{"descriptor_ui":"D003907","descriptor_name":"Dexamethasone","qualifier_ui":"Q000633","qualifier_name":"toxicity","is_major_topic":true},{"descriptor_ui":"D003907","descriptor_name":"Dexamethasone","qualifier_ui":"Q000633","qualifier_name":"toxicity","is_major_topic":true},{"descriptor_ui":"D005234","descriptor_name":"Fatty Liver","qualifier_ui":"Q000139","qualifier_name":"chemically induced","is_major_topic":true},{"descriptor_ui":"D005234","descriptor_name":"Fatty Liver","qualifier_ui":"Q000139","qualifier_name":"chemically induced","is_major_topic":true},{"descriptor_ui":"D005234","descriptor_name":"Fatty Liver","qualifier_ui":"Q000139","qualifier_name":"chemically induced","is_major_topic":true},{"descriptor_ui":"D005234","descriptor_name":"Fatty Liver","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D005234","descriptor_name":"Fatty Liver","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D005234","descriptor_name":"Fatty Liver","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D005234","descriptor_name":"Fatty Liver","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D005234","descriptor_name":"Fatty Liver","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D005234","descriptor_name":"Fatty Liver","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D005234","descriptor_name":"Fatty Liver","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D005234","descriptor_name":"Fatty Liver","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D005234","descriptor_name":"Fatty Liver","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D008099","descriptor_name":"Liver","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D008099","descriptor_name":"Liver","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D008099","descriptor_name":"Liver","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D008099","descriptor_name":"Liver","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D008099","descriptor_name":"Liver","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D008099","descriptor_name":"Liver","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D008099","descriptor_name":"Liver","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D008099","descriptor_name":"Liver","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D008099","descriptor_name":"Liver","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D014409","descriptor_name":"Tumor Necrosis Factor-alpha","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D014409","descriptor_name":"Tumor Necrosis Factor-alpha","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D014409","descriptor_name":"Tumor Necrosis Factor-alpha","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D014409","descriptor_name":"Tumor Necrosis Factor-alpha","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D014409","descriptor_name":"Tumor Necrosis Factor-alpha","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D014409","descriptor_name":"Tumor Necrosis Factor-alpha","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D016328","descriptor_name":"NF-kappa B","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D016328","descriptor_name":"NF-kappa B","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D016328","descriptor_name":"NF-kappa B","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":false},{"descriptor_ui":"D016328","descriptor_name":"NF-kappa B","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D016328","descriptor_name":"NF-kappa B","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D016328","descriptor_name":"NF-kappa B","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D017208","descriptor_name":"Rats, Wistar","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017208","descriptor_name":"Rats, Wistar","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017208","descriptor_name":"Rats, Wistar","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051381","descriptor_name":"Rats","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051381","descriptor_name":"Rats","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051381","descriptor_name":"Rats","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D053583","descriptor_name":"Interleukin-1beta","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D053583","descriptor_name":"Interleukin-1beta","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D053583","descriptor_name":"Interleukin-1beta","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D058988","descriptor_name":"Phosphodiesterase 4 Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D058988","descriptor_name":"Phosphodiesterase 4 Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D058988","descriptor_name":"Phosphodiesterase 4 Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D059865","descriptor_name":"Endoplasmic Reticulum Stress","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true},{"descriptor_ui":"D059865","descriptor_name":"Endoplasmic Reticulum Stress","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true},{"descriptor_ui":"D059865","descriptor_name":"Endoplasmic Reticulum Stress","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1016/j.lfs.2025.123634","doi":"https://doi.org/10.1016/j.lfs.2025.123634","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.lfs.2025.123634","pdf_url":null,"source":{"id":"https://openalex.org/S175775512","display_name":"Life Sciences","issn_l":"0024-3205","issn":["0024-3205","1879-0631"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-70","russia-white-list-1"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Life Sciences","raw_type":"journal-article"},{"id":"pmid:40233857","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/40233857","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Life sciences","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.1016/j.lfs.2025.123634","doi":"https://doi.org/10.1016/j.lfs.2025.123634","is_oa":true,"landing_page_url":"https://doi.org/10.1016/j.lfs.2025.123634","pdf_url":null,"source":{"id":"https://openalex.org/S175775512","display_name":"Life Sciences","issn_l":"0024-3205","issn":["0024-3205","1879-0631"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-70","russia-white-list-1"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Life Sciences","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.98580002784729}],"sustainable_development_goals_aurora":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.5400000214576721}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":40,"referenced_works":["https://openalex.org/W1618134065","https://openalex.org/W1769783081","https://openalex.org/W1990714106","https://openalex.org/W1998812648","https://openalex.org/W2041802771","https://openalex.org/W2074966179","https://openalex.org/W2108527555","https://openalex.org/W2125813424","https://openalex.org/W2144827966","https://openalex.org/W2150202137","https://openalex.org/W2150405273","https://openalex.org/W2167442442","https://openalex.org/W2169310017","https://openalex.org/W2274923892","https://openalex.org/W2329012680","https://openalex.org/W2337911599","https://openalex.org/W2560738399","https://openalex.org/W2608088648","https://openalex.org/W2691474923","https://openalex.org/W2809032618","https://openalex.org/W2809439660","https://openalex.org/W2897406695","https://openalex.org/W2976445574","https://openalex.org/W2995432653","https://openalex.org/W3026572993","https://openalex.org/W3164386904","https://openalex.org/W3183677209","https://openalex.org/W3185428351","https://openalex.org/W3216388135","https://openalex.org/W4214731213","https://openalex.org/W4214868825","https://openalex.org/W4296389389","https://openalex.org/W4360816348","https://openalex.org/W4378349216","https://openalex.org/W4385446443","https://openalex.org/W4387589472","https://openalex.org/W4389196200","https://openalex.org/W4392213448","https://openalex.org/W4393098531","https://openalex.org/W4398247793"],"related_works":["https://openalex.org/W2348005255","https://openalex.org/W2100610477","https://openalex.org/W2065989646","https://openalex.org/W2100613121","https://openalex.org/W2126482145","https://openalex.org/W2071245882","https://openalex.org/W1990017958","https://openalex.org/W2122461299","https://openalex.org/W2796776231","https://openalex.org/W1977028102"],"abstract_inverted_index":{"INTRODUCTION:":[0],"High-dose":[1],"dexamethasone":[2],"(DEX)":[3],"is":[4,101],"used":[5],"for":[6],"management":[7,282],"of":[8,28,53,72,115,129,140,151,174,185,206,231,237,251,261,267,278,283],"severe":[9],"conditions.":[10],"However,":[11],"the":[12,24,50,80,89,152,164,183,196,213,255,273],"multisystem":[13],"adverse":[14],"effects":[15,52],"induced":[16,95,221,269],"by":[17,96,121,178,222,245],"glucocorticoids":[18],"represent":[19],"a":[20,56,264],"hindering":[21],"stone":[22],"toward":[23],"effective":[25],"clinical":[26],"use":[27,280],"such":[29],"agents.":[30],"Various":[31],"initiatives":[32],"have":[33],"been":[34],"taken":[35],"to":[36,48,60,104,127,182,195],"ameliorate":[37],"these":[38],"complications":[39],"with":[40,149],"limited":[41],"success.":[42],"AIM:":[43],"The":[44,70,113,167,218,249],"present":[45],"study":[46,253],"aims":[47],"explore":[49],"beneficial":[51],"roflumilast":[54],"(ROF),":[55],"phosphodiesterase-4":[57],"(PDE-4)":[58],"inhibitor,":[59],"combat":[61],"DEX-induced":[62],"steatohepatitis,":[63],"metabolic":[64,219,258],"abnormalities":[65,85,220],"and":[66,75,82,134,157,190,210,228,257,276],"aortic":[67,83],"degeneration.":[68],"RESULTS:":[69],"application":[71,236],"ROF":[73,122,165,201,246,262],"(2.5":[74],"5":[76],"mg/kg)":[77],"has":[78,180],"reverted":[79],"hepatic":[81],"histopathological":[84],"as":[86,88,136,138,170,172],"well":[87,137,171],"rise":[90],"in":[91,163,263,281],"serum":[92],"liver":[93],"enzymes":[94],"DEX.":[97],"Such":[98],"palliative":[99],"effect":[100],"probably":[102],"attributed":[103],"PDE-4":[105],"inhibition":[106,128],"(\u2191cAMP)":[107],"that":[108,159],"subsequently":[109],"regulates":[110],"multiple":[111],"effectors.":[112],"chemotaxis":[114],"inflammatory":[116,153,175],"cells":[117,214],"(MCP-1)":[118],"was":[119,125,147],"inhibited":[120,204],"treatments":[123,202],"which":[124],"linked":[126],"extracellular":[130],"ROS":[131],"production":[132],"(MDA":[133],"NO)":[135],"restoration":[139],"cellular":[141],"antioxidant":[142],"defense":[143],"(GSH).":[144],"DEX":[145,179,223,279],"challenge":[146],"associated":[148],"activation":[150,173,184,205],"pathways":[154,176],"including":[155,224],"TNF-\u03b1/NF-\u03baB":[156],"NLRP3/IL-1\u03b2":[158],"were":[160,242],"significantly":[161,243],"dampened":[162],"groups.":[166],"oxidative":[168],"stress":[169,188,208],"exerted":[177],"contributed":[181],"endoplasmic":[186],"reticulum":[187],"(CHOP":[189],"PERK)":[191],"posing":[192],"more":[193],"threats":[194],"insulted":[197],"cells,":[198],"however,":[199],"fortunately,":[200],"showed":[203],"ER":[207],"sensors":[209],"thereby":[211],"abstaining":[212],"from":[215],"inevitable":[216],"damage.":[217],"elevated":[225],"fasting":[226],"insulin":[227],"heightened":[229],"AUC":[230],"blood":[232],"glucose":[233,239],"level":[234],"upon":[235],"oral":[238],"tolerance":[240],"test":[241],"improved":[244],"treatment.":[247],"CONCLUSION:":[248],"findings":[250],"our":[252],"depicted":[254],"hepatoprotective":[256],"regulating":[259],"potentials":[260],"rat":[265],"model":[266],"DEX-":[268],"steatohepatitis.":[270],"Thereby,":[271],"enhancing":[272],"overall":[274],"efficacy":[275],"safety":[277],"various":[284],"disorders.":[285]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":1}],"updated_date":"2026-10-16T09:59:22.235173","created_date":"2025-10-10T00:00:00"}