LCN2 as a Potential Diagnostic Biomarker for Ulcerative Colitis-Associated Carcinogenesis Related to Disease Duration

BackgroundPatients with long-duration ulcerative colitis (UC) had a higher risk of developing ulcerative colitis-associated carcinogenesis (UCAC) when compared to those with short-duration UC. This study aimed to discover the biomarker for cancer surveillance related to disease duration.MethodsThe microarrays were divided into short-duration (<10 years) UC, long-duration (≥10 years) UC, UCAC, and normal groups in the Gene Expression Omnibus (GEO) datasets. Differentially expressed genes (DEGs) of GEO and the hub genes of the selected weighted gene co-expression network analysis (WGCNA) were intersected to obtain the overlapping genes. Among these genes, the key gene was identified by using the protein–protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the cytoHubba of Cytoscape, and the expression levels. Also, immunofluorescence of human colonic mucosa and animal experiment were used to validate the expression trend of the key gene in the progress of UC developing into UCAC.ResultsLipocalin-2 (LCN2) was more relevant with disease duration of UC and significantly negatively correlated with the risk of UCAC. The expression level of LCN2 in short-duration UC was higher than that of long-duration UC (P < 0.01), long-duration UC was higher than that of UCAC (P = 0.001), and UC and UCAC were all higher than that of the normal (P < 0.001). We then discovered that the expression trend of LCN2 in blood and stool samples was consistent with that in colorectal mucosa.ConclusionThe research indicates that LCN2 could be a novel biomarker to evaluate cancer surveillance related to disease duration of developing UC into UCAC. Compared with that of blood samples, stool detection of LCN2 may have more advantages for diagnosis value of early stage of UCAC as a complement to colonoscopy surveillance.

Induction of remission with tacrolimus in a patient with severe acute, cortisone refractory ulcerative colitis and severe Covid-19 pneumonia: a case report

Background Therapy regimens used in patients with inflammatory Bowel Disease (IBD) have been associated with enhanced risk of viral infections or viral reactivation. Moreover, it is uncertain whether IBD patients have increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or infected patients may have an increased risk for severe coronavirus disease 2019 (Covid-19). Managing severe acute flare in ulcerative colitis during the Covid-19 pandemic is a challenge for clinicians and their patients. The results of the published studies mainly report on the role of the prior medication, but not how to treat severe acute flare of IBD patients with severe Covid-19 pneumonia. Case presentation We report the case of a 68-year-old patient with a long history of ulcerative colitis. He was initially admitted to an external hospital because of severe acute flare. The initiation of a high-dose oral cortisone therapy did not improve the clinical symptoms. During the inpatient treatment, he was tested positive for SARS-CoV-2. At admission to our hospital the patient showed severe flare of his ulcerative colitis and increased Covid-19 symptoms. A cortisone-refractory course was noticed. After detailed multidisciplinary risk–benefit assessment, we initiated an intravenous tacrolimus therapy and dose of prednisolone was tapered gradually. After clinical response, the therapy was adjusted to infliximab. Additionally, the Covid-19 pneumonia was kept under control despite immunosuppression and the patient could be discharged in clinical remission. Conclusions This case suggest the use of tacrolimus as a bridging therapeutic option for severe acute, cortisone refractory ulcerative colitis in Covid-19 patients. Nevertheless, the best treatment strategy for IBD patients presenting a flare during the outbreak has yet to be defined. Further data for IBD patients under calcineurin inhibitor therapy are urgently needed.

Tofacitinib Inhibits Leukocyte Trafficking Across the Intestinal Endothelial Barrier in a Specific Cohort of Ulcerative Colitis Patients

Lay Summary The JAK/STAT inhibitor tofacitinib, recently approved for the treatment of ulcerative colitis, is found to modulate the intestinal endothelial barrier functions in directing the leukocyte adhesion and transmigration in ulcerative colitis patients displaying high levels of endothelial STAT3/STAT6 phosphorylation.

Bacteriophages in Gut Microbiome Interactions in Patients with Inflammatory Bowel Disease: Differences by Sex and The Disease Type

Background: Inflammatory bowel disease (IBD), known as the disease of the century, is a complex condition that affects millions of people worldwide. IBD is influenced by numerous factors such as genetics, lifestyle, and the gut microbial community, yet the role of microorganisms in driving and controlling the disease remains poorly understood. As we know, preceding studies have mainly focused on assessing gut bacteria and less on bacteriophages or fungi, and no study on interactions of the gut microbial community in patients with IBD has looked at bacteriophages in addition to bacteria and fungi by sex. No distinct microbial regulatory candidate has been proposed so far.Results: Here, metagenomic data were obtained from 456 stool samples of 84 white race volunteers (40 females and 44 males) with no treatment history before sampling. Participants were studied by sex and the disease type using bioinformatics methods. Differences in interactions of bacteriophages, bacteria, fungi, and archaea in the gut of males and females with Crohn's disease were remarkable, indicating the necessity for different therapies for both groups. While, little difference was seen in the gut microbiome relations in females and males with ulcerative colitis.Conclusions: The fungal strain Malassezia globose CBS 7966 beside the bacterial species Bacteroides stercorisin ulcerative colitis and Parabacteroides phage YZ-2015b in Crohn's disease were the sex-independent regulatory candidates. Uncultured crAssphage was recommended as a sex-dependent regulatory candidate for IBD in men. However, the fungus Wickerhamomycesciferrii which had proposed as regulatory candidate in Crohn's disease, was age-dependent in females. Four bacteriophages, such as Escherichia phage pro147, were suggested for study candidates in the metabolism of IBD.

The Role of Innate and Adaptive Immune Cells in the Pathogenesis and Development of the Inflammatory Response in Ulcerative Colitis

Ulcerative colitis (UC) is a chronic inflammatory disease with an underlying excessive immune response directed against resident microbiota and/or dietary antigens. Both innate and adaptive immune cells play a crucial role in the pathogenesis of UC. In the case of innate immune response cells, neutrophils, dendritic cells, macrophages have a crucial impact on the development of the disease, as well as innate lymphoid cells, which have received a particular attention in recent years. On the other hand, mechanisms of the adaptive immune response involve cells such as: cytotoxic lymphocytes, regulatory lymphocytes Treg, or helper lymphocytes Th–Th2, Th9, Th17, Th22, among which significant discoveries about Th9 and Th17 lymphocytes have been made in recent years. Due to the presence of antibodies directed against resident microbiota or one’s own tissues, the influence of B lymphocytes on the development of UC is also highlighted. Additionally, the impact of cytokines on shaping the immune response as well as sustaining inflammation seems to be crucial. This review briefly describes the current state of knowledge about the involvement of the innate and adaptive immune systems in the pathogenesis of UC. The review is based on personal selection of literature that were retrieved by a selective search in PubMed using the terms “ulcerative colitis” and “pathogenesis of ulcerative colitis”. It included systematic reviews, meta-analyses and clinical trials. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents.