Therapeutic potential of the secreted Kazal-type serine protease inhibitor SPINK4 in colitis.

Mucus injury associated with goblet cell (GC) depletion constitutes an early event in inflammatory bowel disease (IBD). Using single-cell sequencing to detect critical events in mucus dysfunction, we discover that the Kazal-type serine protease inhibitor SPINK4 is dynamically regulated in colitic intestine in parallel with disease activities. Under chemically induced colitic conditions, the grim status in Spink4-conditional knockout mice is successfully rescued by recombinant murine SPINK4.

Stanniocalcin-1 Promotes PARP1-Dependent Cell Death via JNK Activation in Colitis.

Stanniocalcin-1 (STC1) is upregulated by inflammation and modulates oxidative stress-induced cell death. Herein, the function of STC1 in colitis and stress-induced parthanatos, a newly identified type of programmed necrotic cell death dependent on the activation of poly-ADP ribose polymerase-1 (PARP1) is investigated. Results show that STC1 expression is markedly increased in the inflamed colonic mucosa of Crohn's disease (CD) patients and chemically-induced mice colitis models.

Protocadherin 20 maintains intestinal barrier function to protect against Crohn's disease by targeting ATF6.

Background: Intestinal barrier dysfunction plays a central role in the pathological onset of Crohn's disease. We identify the cadherin superfamily member protocadherin 20 (PCDH20) as a crucial factor in Crohn's disease. Here we describe the function of PCDH20 and its mechanisms in gut homeostasis, barrier integrity, and Crohn's disease development.

Recent developments on BMPs and their antagonists in inflammatory bowel diseases.

Inflammatory bowel diseases (IBDs), including ulcerative colitis, and Crohn's disease, are intestinal disorders characterized by chronic relapsing inflammation. A large proportion of patients with IBD will progress to develop colitis-associated colorectal cancer due to the chronic intestinal inflammation. Biologic agents that target tumour necrosis factor-α, integrin α4β7, and interleukin (IL)12/23p40 have been more successful than conventional therapies in treating IBD.

A Novel Nomogram Combining Mucus Barrier Index for Predicting Treatment Failures in Ulcerative Colitis.

Background: Treatment failures (TFs) generally exist in the course of ulcerative colitis (UC), while early reliable predictors of TFs are still lacking. We aimed to generate nomograms for the prediction of TFs.

Methods: In this retrospective case-control study, the endpoint was the occurrence of TFs, which included medically associated treatment failures and surgery-associated treatment failures (colectomy).

Role of Rho GTPases in inflammatory bowel disease.

Rat sarcoma virus homolog (Rho) guanosine triphosphatases (GTPases) function as "molecular switch" in cellular signaling regulation processes and are associated with the pathogenesis of inflammatory bowel disease (IBD). This chronic intestinal tract inflammation primarily encompasses two diseases: Crohn's disease and ulcerative colitis. The pathogenesis of IBD is complex and considered to include four main factors and their interactions: genetics, intestinal microbiota, immune system, and environment.

Multi-Omics Analysis of Western-style Diet Increased Susceptibility to Experimental Colitis in Mice.

Background: Western-style diet (WSD) is associated with inflammatory bowel disease (IBD) prevalence. However, the impact of WSD on IBD development and its underlying mechanism remain unclear. Transcriptomics and metabolomics could be beneficial for identifying key factors in WSD-related experimental IBD susceptibility.

Development and validation of a non-invasive biomarker-based model to identify endoscopic recurrences of Crohn's disease.

Background: Endoscopic recurrence is common in postoperative patients with Crohn's disease (CD). Monitoring endoscopic recurrence is important for selecting an appropriate treatment to prevent the development of postoperative disease. The aim of this study was to develop and validate a diagnostic model to identify endoscopic recurrence.

Serum exosomal microRNA-144-3p: a promising biomarker for monitoring Crohn's disease.

Background: Crohn's disease (CD) has a tendency for recurrence and requires adequate monitoring and personalized treatment. Since endoscopy is considerably invasive, serum biomarkers are required as alternatives for CD monitoring. Toward this, exosomal microRNAs (miRNAs) may serve as promising candidates.

Hypermethylation of miR-145 promoter-mediated SOX9-CLDN8 pathway regulates intestinal mucosal barrier in Crohn's disease.

Background: Intestinal barrier impairment plays an essential role in the pathogenesis of Crohn's disease (CD), and claudins (CLDNs) dysfunction contributes to intestinal mucosa injury. SOX9, an important transcription factor, is upregulated in the disease-affected colon of patients with CD; however, its precise role in CD remains largely unknown. Our aim was to explore the interaction between SOX9 and CLDNs, and further elucidate the underlying mechanisms in CD.

Emerging roles of the Hedgehog signalling pathway in inflammatory bowel disease.

The Hedgehog (Hh) signalling pathway plays a critical role in the growth and patterning during embryonic development and maintenance of adult tissue homeostasis. Emerging data indicate that Hh signalling is implicated in the pathogenesis of inflammatory bowel disease (IBD). Current therapeutic treatments for IBD require optimisation, and novel effective drugs are warranted.

A Novel Model Based on Serum Biomarkers to Predict Primary Non-Response to Infliximab in Crohn's Disease.

Background: Infliximab is effective in inducing and maintaining remission in patients with Crohn's disease (CD), but primary non-response (PNR) occurs in 10-30% of cases. We investigated whether serum biomarkers are effective in predicting PNR in patients with CD.

Methods: From January 2016 to April 2020, a total of 260 patients were recruited to this prospective and retrospective cohort study.

MALAT1 Maintains the Intestinal Mucosal Homeostasis in Crohn's Disease via the miR-146b-5p-CLDN11/NUMB Pathway.

Background And Aims: Intestinal homeostasis disorder is critical for developing Crohn's disease [CD]. Maintaining mucosal barrier integrity is essential for intestinal homeostasis, preventing intestinal injury and complications. Among the remarkably altered long non-coding RNAs [lncRNAs] in CD, we aimed to investigate whether metastasis-associated lung adenocarcinoma transcript 1 [MALAT1] modulated CD and consequent disruption of intestinal homeostasis.

Platelet-to-lymphocyte percentage ratio index: a simple non-invasive index to monitor the endoscopic activity in Crohn's disease.

Background: Recent evidence has shown that the complete blood count (CBC) is abnormal in patients with Crohn's disease (CD). We aimed to investigate an effective CBC parameter and explore its impact on disease activity in a large CD cohort.

Methods: We performed a retrospective analysis of patients with established CD who underwent clinically indicated endoscopy at four tertiary centres in China between 2016 and 2020.

Fecal Microbiota Alterations Associated With Clinical and Endoscopic Response to Infliximab Therapy in Crohn's Disease.

Background: Gut microbiota dysbiosis is associated with the occurrence and development of Crohn disease (CD). Currently, infliximab (IFX) is used more and more to treat CD; however, gut microbiota alterations during IFX therapy are variable and sometimes even contradictory. We longitudinally identified microbial changes during IFX therapy associated with the clinical and endoscopic response to IFX treatment in CD.

Which long noncoding RNAs and circular RNAs contribute to inflammatory bowel disease?

Inflammatory bowel disease (IBD), a chronic relapsing gastrointestinal inflammatory disease, mainly comprises ulcerative colitis (UC) and Crohn's disease (CD). Although the mechanisms and pathways of IBD have been widely examined in recent decades, its exact pathogenesis remains unclear. Studies have focused on the discovery of new therapeutic targets and application of precision medicine.

Serum Biomarkers for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic, inflammatory disorder of the gastrointestinal tract. As the novel therapeutic goal and biologicals are widely recognized, accurate assessment of disease and prediction of therapeutic response have become a crucial challenge in clinical practice. Also, because of the continuously rising incidence, convenient and economical methods of diagnosis and clinical assessment are urgently needed.

Circulating microRNA146b-5p is superior to C-reactive protein as a novel biomarker for monitoring inflammatory bowel disease.

Background: Owing to the importance of early treatment, simple and reliable methods for monitoring inflammatory bowel disease (IBD) are needed.

Aims: To determine whether circulating microRNAs are reliable biomarkers for IBD monitoring.

Methods: Serum levels of 17 candidate microRNAs were measured by quantitative real-time polymerase chain reaction in a discovery cohort (n = 120).

Cytokine IL9 Triggers the Pathogenesis of Inflammatory Bowel Disease Through the miR21-CLDN8 Pathway.

Background: Cytokine interleukin-9 (IL9) plays an essential role in the pathogenesis of inflammatory bowel disease. However, the molecular mechanism underlying the IL9 pathway remains unknown. Here, we initiate a series of studies to characterize the essential components of this pathway.