Glucocorticoid-Induced Leucine Zipper as a Druggable Target in Inflammatory Bowel Diseases

2020 ◽  
Vol 26 (7) ◽  
pp. 1017-1025 ◽  
Author(s):  
Simona Ronchetti ◽  
Marco Gentili ◽  
Erika Ricci ◽  
Graziella Migliorati ◽  
Carlo Riccardi

Abstract Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex pathogenesis, affecting people of all ages. They are characterized by alternating phases of clinical relapse and remission, depending on the fine balance between immune cells and the gut microbiota. The cross talk between cells of the immune system and the gut microbiota can result in either tolerance or inflammation, according to multifactorial triggers, ranging from environmental factors to genetic susceptibility. Glucocorticoid (GC) administration remains the first-line treatment for IBDs, although long-term use is limited by development of serious adverse effects. Recently, new alternative pharmacological therapies have been developed, although these are not always effective in IBD patients. There is a constant demand for effective new drug targets to guarantee total remission and improve the quality of life for IBD patients. The glucocorticoid-induced leucine zipper (GILZ) has been implicated as a promising candidate for this purpose, in view of its powerful anti-inflammatory effects that mimic those of GCs while avoiding their unwanted adverse reactions. Here we present and discuss the latest findings about the involvement of GILZ in IBDs.

2016 ◽  
Vol 150 (4) ◽  
pp. S995
Author(s):  
Francesca Padovese ◽  
Maria Grazia Vettorato ◽  
Greta Lorenzon ◽  
Francesco Cavallin ◽  
Ottavia Bartolo ◽  
...  

2015 ◽  
Vol 24 (2) ◽  
pp. 165-170 ◽  
Author(s):  
Mariabeatrice Principi ◽  
Giuseppe Losurdo ◽  
Rosa Federica La Fortezza ◽  
Pasquale Lopolito ◽  
Rosa Lovero ◽  
...  

Background & Aims: Infliximab (IFX) is an anti-tumor necrosis factor alpha agent used in inflammatory bowel diseases (IBD) therapy. Usually, it is administered over a 2-hour intravenous infusion. However, shortening the infusion duration to 1 hour has proved to be feasible and safe. In the present study we evaluated whether shortening the IFX infusion could affect the patients' quality of life (QoL) compared to the standard protocol.Methods: Subjects affected by IBD receiving IFX were prospectively recruited. The main criterion to shorten the infusion was the absence of IFX-related adverse reactions during the previous three 2-h infusions. For each patient, demographic, clinical and anthropometric data were collected. A questionnaire investigating their overall/job/social/sexual QoL was administered. Ordinal regression was performed with odds ratios (OR) for significant independent variables.Results: Eighty-one patients were included (46 with ulcerative colitis - UC, 35 with Crohn's disease - CD). Sixteen received the 2-h infusion due to previous adverse reactions, and the remaining 65 underwent the 1-h schedule. Shortening the infusion to 1 hour determined a better QoL (OR=0.626). However, the QoL was negatively influenced by age (OR=1.023), female sex (OR=2.04) and severe disease activity (OR=7.242). One-hour IFX infusion induced a better outcome on work (OR=0.588) and social (OR=0.643) QoL. Long-standing disease was correlated with a slightly better sexual QoL (OR=0.93). Conversely, older age (OR=1.046), severe clinical score (OR=15.579), use of other immunomodulators (OR=3.693) and perianal CD (OR=3.265) were related to an unsatisfactory sexual life. The total number of infusions (OR=0.891), proctitis (OR=0.062) or pancolitis (OR=0.1) minimized the perception of infusion-related side effects.Conclusion: The 1-h short infusion improves overall, social and job QoL, so that, when indicated, it should be recommended.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 412
Author(s):  
Katarzyna Dziąbowska-Grabias ◽  
Małgorzata Sztanke ◽  
Przemysław Zając ◽  
Michał Celejewski ◽  
Katarzyna Kurek ◽  
...  

Inflammatory bowel diseases (IBD) are a group of chronic, incurable diseases of the digestive tract, the etiology of which remains unclear to this day. IBD result in significant repercussions on the quality of patients’ life. There is a continuous increase in the incidence and prevalence of IBD worldwide, and it is becoming a significant public health burden. Pharmaceuticals commonly used in IBD management, for example, mesalamine, sulfasalazine, corticosteroids, and others, expose patients to diverse, potentially detrimental side effects and frequently do not provide sufficient disease control. The chronic inflammation underlies the etiology of IBD and closely associates with oxidative/nitrosative stress and a vast generation of reactive oxygen/nitrogen species. Relative to this, several substances with antioxidant and anti-inflammatory properties are now intensively researched as possible adjunctive or independent treatment options in IBD. Representatives of several different groups, including natural and chemical compounds will be characterized in this dissertation.


2020 ◽  
Vol 21 (8) ◽  
pp. 2940
Author(s):  
Antonelly Cassio Alves de Carvalho ◽  
Gabriela Achete de Souza ◽  
Samylla Vaz de Marqui ◽  
Élen Landgraf Guiguer ◽  
Adriano Cressoni Araújo ◽  
...  

Inflammatory bowel diseases (IBD) are characterized by a chronic and recurrent gastrointestinal condition, including mainly ulcerative colitis (UC) and Crohn’s disease (CD). Cannabis sativa (CS) is widely used for medicinal, recreational, and religious purposes. The most studied compound of CS is tetrahydrocannabinol (THC) and cannabidiol (CBD). Besides many relevant therapeutic roles such as anti-inflammatory and antioxidant properties, there is still much controversy about the consumption of this plant since the misuse can lead to serious health problems. Because of these reasons, the aim of this review is to investigate the effects of CS on the treatment of UC and CD. The literature search was performed in PubMed/Medline, PMC, EMBASE, and Cochrane databases. The use of CS leads to the improvement of UC and CD scores and quality of life. The medical use of CS is on the rise. Although the literature shows relevant antioxidant and anti-inflammatory effects that could improve UC and CD scores, it is still not possible to establish a treatment criterion since the studies have no standardization regarding the variety and part of the plant that is used, route of administration and doses. Therefore, we suggest caution in the use of CS in the therapeutic approach of IBD until clinical trials with standardization and a relevant number of patients are performed.


2011 ◽  
Vol 6 ◽  
pp. 388-400
Author(s):  
Ludwika Jakubowska-Burek ◽  
Izabella Warmuz-Stangierska ◽  
Elżbieta Kaczmarek ◽  
Marcin A. Kucharski ◽  
Emilia Marcinkowska ◽  
...  

2014 ◽  
Vol 86 (9) ◽  
Author(s):  
Aneta Raczkowska ◽  
Michał Ławiński ◽  
Aleksandra Gradowska ◽  
Urszula Zielińska-Borkowska

AbstractOne of the elements of treatment considering inflammatory bowel diseases is nutritional therapy. The duration of the above-mentioned depends on the prevalence of such symptoms as fever, bowel move-ments, length of the functioning gastrointestinal tract, stoma and intestinal fistula presence. Nutritional therapy is an essential element of successful treatment alongside pharmacological, surgical, and biological therapy, as well as other methods. Crohn's disease and ulcerative colitis considered as chronic diseases, lead towards physical and biopsychosocial disability, being responsible for the reduction in the quality of life.was to determine the quality of life after surgical procedures in case of patients diagnosed with Crohn's disease and ulcerative colitis, subjected to natural and parenteral nutrition.The study group comprised 52 patients from the Department of Gastroen-terology, Military Medical Institute, and Department of Surgery and Clinical Nutrition, Clinical Hospital in Warsaw. The study was performed between October, 2011 and April, 2012. The World Health Organization Quality of Life Instrument - Bref (WHOQOL-BREF) questionnaire was used to deter-mine the patients’ quality of life.A lower quality of life was observed in case of patients subjected to parenteral nutrition, poor education, disease symptoms exacerbation, in the majority-rural inhabitants. The quality of life does not depend on gender, type of disease, family status, and additional medical care.


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