Although development of biologics has importantly improved the effectiveness in inducing and maintaining remission in inflammatory bowel disease (IBD), biologic therapies still have several limitations. Effective, low-cost drug therapy with good safety profile and compliance is therefore a substantial unmet medical need. A promising target for IBD treatment strategies are Janus kinase (JAK) inhibitors, which are small molecules that interact with cytokines implicated in pathogenesis of IBD. In contrast to monoclonal antibodies, which are able to block a single cytokine, JAK inhibitors have the potential to affect multiple cytokine-dependent immune pathways, which may improve the therapeutic response in some IBD patients. Tofacitinib, inhibiting signaling via different types of JAKs, has been already approved for ulcerative colitis, and several other small-molecule are still under investigation. However, one of the main concerns about using JAK inhibitors is the risk of thromboembolic events. Moreover, patients with COVID-19 appear to have an increased susceptibility for immunothrombosis. Therefore, thrombotic complications may become a serious limitation in the use of JAK inhibitors in the SARS-CoV-2 pandemic. As many questions about safety and efficacy of small molecules still remain unclear, in our review we present the current data regarding approved JAK inhibitors, as well as those in clinical development for the treatment of IBD.

In the last few decades, the practical use of stem cells (SCs) in the clinic has attracted significant attention in the regenerative medicine due to the ability of these cells to proliferate and differentiate into other cell types. However, recent findings have demonstrated that the therapeutic capacity of SCs may also be mediated by their ability to secrete biologically active factors, including extracellular vesicles (EVs). Such submicron circular membrane-enveloped vesicles may be released from the cell surface and harbour bioactive cargo in the form of proteins, lipids, mRNA, miRNA, and other regulatory factors. Notably, growing evidence has indicated that EVs may transfer their bioactive content into recipient cells and greatly modulate their functional fate. Thus, they have been recently envisioned as a new class of paracrine factors in cell-to-cell communication. Importantly, EVs may modulate the activity of immune system, playing an important role in the regulation of inflammation, exhibiting broad spectrum of the immunomodulatory activity that promotes the transition from pro-inflammatory to pro-regenerative environment in the site of tissue injury. Consequently, growing interest is placed on attempts to utilize EVs in clinical applications of inflammatory-related dysfunctions as potential next-generation therapeutic factors, alternative to cell-based approaches. In this review we will discuss the current knowledge on the biological properties of SC-derived EVs, with special focus on their role in the regulation of inflammatory response. We will also address recent findings on the immunomodulatory and pro-regenerative activity of EVs in several disease models, including in vitro and in vivo preclinical, as well as clinical studies. Finally, we will highlight the current perspectives and future challenges of emerging EV-based therapeutic strategies of inflammation-related diseases treatment.

Inflammatory bowel diseases (IBD) are characterized by cumbersome symptoms with varying severity. However, regardless of the intensity of disease activity the patients may experience extraintestinal manifestations which further deteriorate the patients’ quality of life. According to the literature, nearly half of the patients with IBD will develop at least one extraintestinal manifestation in their lifespan. Apart from the most common and often well-surveilled such as articular, ocular, dermatologic or hepatic entities, the neurological and psychiatric ones are often disregarded or not sought. We reviewed the latest literature on the most frequent disorders occurring in patients with IBD covering these two fields.

Background The association between various rheumatic diseases and inflammatory bowel diseases is suggested by many clinical and experimental observations. Immunological disturbances play a crucial role in the pathogenesis of both rheumatic diseases and inflammatory bowel diseases (IBD), like ulcerative colitis (UC) and Crohn disease (CD). Numerous scientific reports suggest similar pathogenesis of IBD and spondyloarthropathies (SpA), but the patomechanisms linking these two groups of diseases are still being examined. Objectives The aim of our study was to assess the prevalence of coexistence of various rheumatic diseases and inflammatory bowel diseases in a group of rheumatic patients (pts). Methods This retrospective study was based on the analysis of 4000 clinical histories of patients with various rheumatic diseases, hospitalized in the University Department of Rheumatology and Connective Tissue Diseases between the years 2005 and 2011. We searched for the coexistence of various rheumatic diseases and inflammatory bowel disease (IBD) with clinically confirmed diagnosis. The diagnosis of all rheumatic diseases was established according to the current classification criteria. The diagnosis of IBD - UC or CD was confirmed by histopathological examination of gut. Results The coexistence of IBD with a rheumatic disease was found in 15 (0,38%) of all rheumatic pts. Among them there were 13 pts with ulcerative colitis (UC) and 2 pts with Crohn disease (CD). Both pts with the diagnosis of CD had ankylosing spondylitis (AS). Among 4000 pts with various rheumatic diseases there were 921 pts with rheumatoid arthritis (RA); 342 pts with systemic lupus erythematosus (SLE); 95 pts with AS; 65 pts with psoriatic arthritis (PsA); 35 pts with Wegener’s granulomatosis. We found the association of UC with RA in 1 patient (0,11% all RA pts), with SLE in 5 pts (1,46% all SLE pts), with Wegener’s granulomatosis in 1 patient, with undifferentiated ANCA (+) vasculitis in 1 patient, with PsA in 1 patient. In 4 pts with UC enteric arthropathy was diagnosed. There were no pts with the coexistence of UC and AS. In the group of 5 pts with SLE there were only women, in the age of 28-49 years old. The coexistence of SLE was observed only with UC. The diagnosis of IBD had been established prior to the diagnosis of SLE in 80% cases, 2 to 11 years before the first symptoms of SLE. In 3/5 of pts renal involvement, leukopenia and thrombocytopenia were seen. The coexistence of IBD with inflammatory SpA we found in 4,4% of all SpA pts. Enteric arthropathy symptoms occurred 1 to 16 years before the diagnosis of IBD was established. AS and PsA diagnosis was made at the same time or later (0-4 years) than diagnosis of IBD. All pts with AS had the axial form of the disease, without peripheral joint involvement. Conclusions We conclude that the coexistence of various rheumatic diseases and inflammatory bowel diseases with clinically confirmed diagnosis is relatively low. Inflammatory bowel diseases mainly coexist with inflammatory spondyloarthopati...