Inflammatory bowel disease (IBD) is a chronic inflammatory state of the gastrointestinal tract and can be classified into 2 main clinical phenomena: Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis of IBD, including CD and UC, involves the presence of pathogenic factors such as abnormal gut microbiota, immune response dysregulation, environmental changes, and gene variants. Although many investigations have tried to identify novel pathogenic factors associated with IBD that are related to environmental, genetic, microbial, and immune response factors, a full understanding of IBD pathogenesis is unclear. Thus, IBD treatment is far from optimal, and patient outcomes can be unsatisfactory. As result of massive studying on IBD, T helper 17 (Th17) cells and innate lymphoid cells (ILCs) are investigated on their effects on IBD. A recent study of the plasticity of Th17 cells focused primarily on colitis. ILCs also emerging as novel cell family, which play a role in the pathogenesis of IBD. IBD immunopathogenesis is key to understanding the causes of IBD and can lead to the development of IBD therapies. The aim of this review is to explain the pathogenesis of IBD, with a focus on immunological factors and therapies.

Ubiquitin-dependent proteolysis plays an essential role in the regulation of a variety of cellular processes, including cell proliferation, differentiation, and apoptosis (1-3). Ubiquitin (Ub) 3 is covalently attached to target proteins by a cascade enzyme system consisting of Ub-activating (E1), conjugating (E2), and ligating (E3) enzymes (1, 4). Ub E3 ligases that confer the substrate specificity have been grouped into two families; the HECT-domain family that is defined by its homology to E6-associated protein (E6AP) and the RING family carrying RING-finger domain that is essential for the Ub ligase activity (5, 6). One of the well defined RING E3 ligases is the Skp1/Cul1/F-box protein complex, in which Cul1 serves as a scaffold molecule that interacts with Skp1 and a small RING-finger protein Roc1, also known as Hrt1 and Rbx1 (7-9). F-box proteins are recruited to the complex by binding to the Skp1 adaptor protein.At least six Cul members have been identified: Cul1, Cul2, Cul3, Cul4A, Cul4B, and Cul5 (10). Of these, Cul3 is known to mediate the degradation of several proteins, such as cyclin E (11), but the molecular composition of Cul3-based Ub ligase was unknown. Recently, a large family of proteins having BTB (Bric-a-brac/Tramtrack/Broad complex) domain has been identified as novel Cul3-interacting proteins (12). Most BTB proteins, but not all, have additional domains for proteinprotein interaction, such as zinc fingers, Kelch repeats, and MATH motifs. Furthermore, a subset of proteins containing BTB domain has been identified to function as substrate-specific adaptors that bind to Cul3. Specifically, MEL-26, a homolog of human SPOP (speckle-type POZ protein) in Caenorhabditis elegans, was first identified as a BTB protein that serves as a specific adaptor of MEI-1 for the ubiquitination by Cul3-based Ub ligase and subsequent degradation by the proteasome (13). MEI-1 is a subunit of the katanin-like microtubule severing heterodimer MEI-1/MEI-2 that localizes to the spindles and the chromosomes during meiosis (14). SPOP BTB protein has also been shown to mediate the ubiquitination of the Polycomb group BMI and the variant histone MacroH2A (15). In addition, Keap1 BTB protein was shown to recruit Nrf2 to . Nrf2 is a transcription factor that regulates the expression of anti-oxidant genes upon oxidative stress. In Schizosaccharomyces pombe, Btb1p, Btb2p, and Btb3p interact with Cul3, but their functions remain unknown (20). Therefore, so far only a few protein substrates have been shown to interact with BTB proteins for their ubiquitination by Cul3-based Ub ligases.Daxx was originally identified as a protein that binds to the death domain of Fas receptor by yeast two-hybrid screening (21). Daxx interacts with the apoptosis signal-regulating kinase 1 (ASK1) and promotes Fas-mediated apoptosis through the activation of Jun N-terminal kinase (22). Subsequent studies have also shown that Daxx behaves as a proapoptotic protein under various stress conditions (21,(23)(24)(25). On the contrary, homozygous deletio...

Aims/hypothesis Although there is substantial evidence that non-alcoholic fatty liver disease (NAFLD) is associated with impaired glucose homeostasis, the clinical significance of NAFLD in pregnant women has not been well determined. This study investigates the relationship between NAFLD in the first trimester and the subsequent development of gestational diabetes mellitus (GDM). Methods A multicentre, prospective cohort study was conducted in which singleton pregnant Korean women were assessed for NAFLD at 10-14 weeks using liver ultrasound, fatty liver index (FLI) and hepatic steatosis index (HSI). Maternal plasma adiponectin and selenoprotein P concentrations were measured. Participants were screened for GDM using the two-step approach at 24-28 weeks.Results Six hundred and eight women were included in the final analysis. The prevalence of NAFLD was 18.4% (112/608) and 5.9% (36/608) developed GDM. Participants who developed GDM had a higher prevalence of radiological steatosis (55.6% vs 16.1%; p < 0.001) and higher FLI (40.0 vs 10.7; p < 0.001) and HSI (35.5 vs 29.0; p < 0.001). The risk of developing GDM was significantly increased in participants with NAFLD and was positively correlated with the severity of steatosis. This relationship Won Kim and Joong Shin Park contributed equally to this work.Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-018-4779-8) contains peer-reviewed but unedited supplementary material, which is available to authorised users. between NAFLD and GDM remained significant after adjustment for metabolic risk factors, including measures of insulin resistance. Maternal plasma adiponectin and selenoprotein P levels were also correlated with both NAFLD severity and the risk of developing GDM. Conclusions/interpretation NAFLD in early pregnancy is an independent risk factor for GDM. Adiponectin may be a useful biomarker for predicting GDM in pregnant women.

Vulvar hematomas are uncommon outside of the obstetric population and may be the result of trauma to the perineum. Vulvar hematomas most often present with low abdominal pain and urologic and neurologic symptoms. The vulva has rich vascularization that is supplied by the pudendal artery, a branch of the anterior division of the internal iliac artery. We describe a rare case of a 15-cm-sized vulvar hematoma with the suggested rupture of a pseudoaneurysm of the left pudendal artery without trauma injury. A 14-year-old girl presented with sudden pain and swelling in her left labium and was successfully treated with selective arterial embolization and surgical evacuation. We provide a literature review and discuss patient treatment and management strategies.

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