Autoimmune and inflammatory diseases of the gastrointestinal tract

1976 ◽  
pp. 203-250 ◽  
Author(s):  
D. P. Jewell ◽  
H. J. F. Hodgson
Keyword(s):  
Gastrointestinal Tract ◽  
Inflammatory Diseases ◽  
Autoimmune And Inflammatory Diseases

scholarly journals Selective Targeting of Epigenetic Readers and Histone Deacetylases in Autoimmune and Inflammatory Diseases: Recent Advances and Future Perspectives

2021 ◽  
Vol 11 (5) ◽  
pp. 336
Author(s):  
Mohammed Ghiboub ◽  
Ahmed M. I. Elfiky ◽  
Menno P. J. de Winther ◽  
Nicola R. Harker ◽  
David F. Tough ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Inflammatory Diseases ◽  
Selective Inhibition ◽  
In Vivo Studies ◽  
Beneficial Effects ◽  
Domain Specific ◽  
Recent Advances ◽  
Autoimmune And Inflammatory Diseases

Histone deacetylases (HDACs) and bromodomain-containing proteins (BCPs) play a key role in chromatin remodeling. Based on their ability to regulate inducible gene expression in the context of inflammation and cancer, HDACs and BCPs have been the focus of drug discovery efforts, and numerous small-molecule inhibitors have been developed. However, dose-limiting toxicities of the first generation of inhibitors, which typically target multiple HDACs or BCPs, have limited translation to the clinic. Over the last decade, an increasing effort has been dedicated to designing class-, isoform-, or domain-specific HDAC or BCP inhibitors, as well as developing strategies for cell-specific targeted drug delivery. Selective inhibition of the epigenetic modulators is helping to elucidate the functions of individual epigenetic proteins and has the potential to yield better and safer therapeutic strategies. In accordance with this idea, several in vitro and in vivo studies have reported the ability of more selective HDAC/BCP inhibitors to recapitulate the beneficial effects of pan-inhibitors with less unwanted adverse events. In this review, we summarize the most recent advances with these strategies, discussing advantages and limitations of these approaches as well as some therapeutic perspectives, focusing on autoimmune and inflammatory diseases.

scholarly journals Roles of XBP1s in Transcriptional Regulation of Target Genes

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 791
Author(s):  
Sung-Min Park ◽  
Tae-Il Kang ◽  
Jae-Seon So
Keyword(s):  
Transcriptional Regulation ◽  
Er Stress ◽  
Target Genes ◽  
Inflammatory Diseases ◽  
Vital Role ◽  
Genes Encoding ◽  
Autoimmune And Inflammatory Diseases ◽  
Active Transcription ◽  
Transcriptional Regulatory Mechanisms ◽  
The Unfolded Protein Response

The spliced form of X-box binding protein 1 (XBP1s) is an active transcription factor that plays a vital role in the unfolded protein response (UPR). Under endoplasmic reticulum (ER) stress, unspliced Xbp1 mRNA is cleaved by the activated stress sensor IRE1α and converted to the mature form encoding spliced XBP1 (XBP1s). Translated XBP1s migrates to the nucleus and regulates the transcriptional programs of UPR target genes encoding ER molecular chaperones, folding enzymes, and ER-associated protein degradation (ERAD) components to decrease ER stress. Moreover, studies have shown that XBP1s regulates the transcription of diverse genes that are involved in lipid and glucose metabolism and immune responses. Therefore, XBP1s has been considered an important therapeutic target in studying various diseases, including cancer, diabetes, and autoimmune and inflammatory diseases. XBP1s is involved in several unique mechanisms to regulate the transcription of different target genes by interacting with other proteins to modulate their activity. Although recent studies discovered numerous target genes of XBP1s via genome-wide analyses, how XBP1s regulates their transcription remains unclear. This review discusses the roles of XBP1s in target genes transcriptional regulation. More in-depth knowledge of XBP1s target genes and transcriptional regulatory mechanisms in the future will help develop new therapeutic targets for each disease.

Risk Factors and Prevention of Pneumocystis jirovecii Pneumonia in Patients With Autoimmune and Inflammatory Diseases

CHEST Journal ◽  
2020 ◽  
Vol 158 (6) ◽  
pp. 2323-2332 ◽  
Author(s):  
Amine Ghembaza ◽  
Mathieu Vautier ◽  
Patrice Cacoub ◽  
Valérie Pourcher ◽  
David Saadoun
Keyword(s):  
Risk Factors ◽  
Inflammatory Diseases ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Autoimmune And Inflammatory Diseases
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