Search

Acute liver failure (ALF) is a complex syndrome characterized by overactivation of innate immunity, and the recruitment and differentiation of immune cells at inflammatory sites. The present study aimed to explore the role of microRNA (miRNA/miR)-21 and its potential mechanisms underlying inflammatory responses in ALF. Baseline serum miR-21 was analyzed in patients with ALF and healthy controls. In addition, miR-21 antagomir was injected via the tail vein into C57BL/6 mice, and lipopolysaccharide/D-galactosamine (LPS/GalN) was injected into mice after 48 h. The expression levels of miR-21, Krüppel-like-factor-6 (KLF6), autophagy-related proteins and interleukin (IL)-23, and hepatic pathology were then assessed in the liver tissue. Furthermore, THP-1-derived macrophages were transfected with a miRNA negative control, miR-21 inhibitor, miR-21 mimics or KLF6 overexpression plasmid, followed by treatment with or without rapamycin, and the expression levels of miR-21, KLF6, autophagy-related proteins and IL-23 were evaluated. The results revealed that baseline serum miR-21 levels were significantly upregulated in patients with ALF. In addition, LPS/GalN-induced ALF was attenuated in the antagomir-21 mouse group. KLF6 was identified as a target of miR-21-5p with one putative seed match site identified by TargetScan. A subsequent luciferase activity assay demonstrated a direct interaction between miR-21-5p and the 3′-UTR of KLF6 mRNA. Further experiments suggested that miR-21 promoted the expression of IL-23 via inhibiting KLF6, which regulated autophagy. In conclusion, in the present study, baseline serum miR-21 levels were highly upregulated in patients with ALF, antagomir-21 attenuated LPS/GalN-induced ALF in a mouse model, and miR-21 could promote the expression of IL-23 via inhibiting KLF6. [ABSTRACT FROM AUTHOR]

Intestinal symbiotic bacteria play a key role in the regulation of immune tolerance in inflammatory bowel disease (IBD) hosts. However, the bacterial strains directly involved in this regulation and their related metabolites are largely unknown. We sought to investigate the effects of intestinal microbial metabolites on intestinal epithelium and to elucidate their therapeutic potential in regulating intestinal mucosal inflammation and immune homeostasis. Here, we used metagenomic data from Crohn's disease (CD) patients to analyze the composition of intestinal flora and identify metabolite profiles associated with disease behavior, and used the mouse model of dextran sodium sulfate (DSS)-induced colitis to characterize the therapeutic effects of the flora metabolite acetyl l -carnitine (ALC) on DSS-induced colitis. We found that intraperitoneal injection of ALC treatment could significantly alleviate the symptoms of DSS-induced colitis in mice, including prevention of weight loss, reduction in disease activity index (DAI) scores, increasing of colonic length, reduction in histological scores, and improvement in intestinal barrier function. Further, transcriptome sequencing analysis and gene silencing experiments revealed that the absence of CADM2 abolished the inhibitory effect of ALC on the TLR-MyD88 pathway in colonic epithelial cells, thereby reducing the release of inflammatory factors in colon epithelial cells. And we confirmed a significant downregulation of CADM2 expression in intestinal tissues of CD patients compared to healthy people in a population cohort. In addition, we also found that ALC increased the ratio of Treg cells in colon, and decreased the ratio of Th17 cells and macrophages, thereby improving the immune tolerance of the organism. The proposed study could be a potential approach for the treatment of CD. [Display omitted] • ALC can alleviate the inflammatory level of colon epithelial by up-regulating CADM2. • CADM2 down-regulates the expression of MyD88 in colonic epithelial cells. • ALC can change the proportion of immune cells in colon LPMC. [ABSTRACT FROM AUTHOR]

Background/Aims: Serum procalcitonin (PCT) is elevated in acute liver failure (ALF), but the expression of PCT in the liver has not been elucidated. We aimed to clarify the regulation of hepatic PCT expression and the cell sources in ALF. Methods: Human monocytic leukemia line U937 cells were treated with 12-O-tetradecanoylphorbol-l3-acetate (PMA) (100 ng/ mL) for 24 h to induce activated macrophages. In the presence of lipopolysaccharide (LPS, 1 μg/mL), activated macrophages and human hepatocyte line L02 cells were incubated with LPS or co-cultured for 0, 2, 6, and 24 h. In an in vivo experiment, male C57BL/6 mice were challenged with intraperitoneal LPS/D-galactosamine (LPS/D-GalN). Serum liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using an automatic chemical analyzer. Inflammatory mediators were measured by real-time PCR and liver histology was examined by hematoxylin-eosin (HE) staining and immunohistochemistry (IHC). Results: LPS induced the upregulation of PCT mRNA in U937-activated macrophages but not in L02 cells. When co-cultured with L02 cells, the expression of PCT mRNA of activated macrophages was upregulated compared to controls; however, the activated macrophages did not induce the expression of PCT mRNA in L02 cells in the presence of LPS. Moreover, serum liver enzymes (ALT, AST), inflammation, necrosis, and hepatic expression of PCT were significantly elevated in the LPS/D-GalN-challenged ALF mouse model. IHC revealed that PCT expression was co-localized with hepatic macrophages. Conclusions: Hepatic PCT expression is upregulated in ALF. Hepatic macrophages but not hepatocytes are the cell source of hepatic PCT expression. [ABSTRACT FROM AUTHOR]

Background and Aim: Behcet's disease is a systemic vasculitis that can involve gastrointestinal tract. This is a systematic review and meta‐analysis evaluating the efficacy and safety of anti‐tumor necrosis factor (TNF) agents in treating patients with intestinal Behcet's disease. Methods: We conducted searches on PubMed, Embase, and Cochrane. Data from eligible studies were used to calculate the pooled estimate of proportions of clinical remission, mucosal healing at Months 3, 6, 12, and 24 as well as the pooled incidence of adverse drug reactions. And subgroup analysis based on the specific type of anti‐TNF agents was performed. Results: Of the 828 studies initially identified, 13 were included finally, all of which were single‐arm cohort studies. The pooled proportions of clinical remission at Months 3, 6, 12, and 24 were 0.61 (95%CI 0.48–0.78), 0.51 (95%CI 0.40–0.66), 0.57 (95%CI 0.48–0.67), and 0.38 (95%CI 0.16–0.88), respectively. The pooled proportions of mucosal healing at Months 3, 6, 12, and 24 were 0.66 (95%CI 0.50–0.86), 0.82 (95%CI 0.48–0.98), 0.65 (95%CI 0.51–0.81), and 0.69 (95%CI 0.39–1.00), respectively. The pooled estimate of proportion of overall adverse drug reactions for infliximab was 0.22 (95%CI 0.07–0.69). Conclusions: Anti‐TNF agents, including infliximab and adalimumab, were an efficient therapy for intestinal Behcet's disease. The safety of anti‐TNF agents used in the treatment of intestinal Behcet's disease was acceptable. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) colitis brings great obstacles for treatment of ulcerative colitis (UC). We aimed to assess the impact of CMV colitis on prognostic outcomes and associated risk factors for UC patients. A consecutive 77 inpatients diagnosed as UC were collected retrospectively from January 2012 to December 2015. About 33 patients were defined with CMV colitis by histological tests of colon mucosa. Clinical characteristics and outcomes were compared between patients with CMV colitis or those without. The primary outcomes were UC-related colectomy or the first time of disease relapse after discharge. 33 CMV colitis patients had higher frequency of recent steroid treatment (81.8% vs. 31.8%, p <.001), older age of onset (45.3 ± 13.0 vs. 44.5 ± 15.7 years, p =.028) and more severe colitis (p <.001) characterized by lower hemoglobin (99.0 ± 23.2 vs. 114.6 ± 22.6 g/L, p =.004), albumin (29.7 ± 4.6 vs. 35.4 ± 6.5 g/L, p <.001), immunoglobulin G [8.8 (5.9–10.6) vs. 12.3 (9.3–16.2) g/L, p =.003] and higher C reactive protein [48.5 (21.6–73.8) vs. 9.1 (3.6–35.0) mg/L, p <.001]. The occurrence of UC-related colectomy in patients with CMV colitis was more frequent (48.5% vs 20.5%, p<.01) and CMV colitis was proved to be one of risk factors of colectomy with a hazard ratio of 3.15 (95%CI 1.387–7.171, p =.006), mainly in a short term period. UC-related complications almost occurred within 1 year since CMV colitis diagnosis. And UC patients with CMV colitis always experienced early relapse. CMV colitis increases the colectomy risk mainly in a short term due to severe inflammatory response, early-onset complications or medication treatment failure. There is also potential correlation between CMV colitis and early relapse. Short-term therapy for UC patients with CMV colitis should be more concerned on controlling systemic inflammation and reducing complications whereas long-term maintenance therapy may not require more aggressive intervention. [ABSTRACT FROM AUTHOR]

Background & Aims: The evaluation of the stage of liver fibrosis is essential in patients with chronic liver disease. However, due to the low quality of ultrasound images, the non‐invasive diagnosis of liver fibrosis based on ultrasound images is still an outstanding question. This study aimed to investigate the diagnostic accuracy of a deep learning‐based method in ultrasound images for liver fibrosis staging in multicentre patients. Methods: In this study, we proposed a novel deep learning‐based approach, named multi‐scale texture network (MSTNet), to assess liver fibrosis, which extracted multi‐scale texture features from constructed image pyramid patches. Its diagnostic accuracy was investigated by comparing it with APRI, FIB‐4, Forns and sonographers. Data of 508 patients who underwent liver biopsy were included from 4 hospitals. The area‐under‐the ROC curve (AUC) was determined by receiver operating characteristics (ROC) curves for significant fibrosis (≥F2) and cirrhosis (F4). Results: The AUCs (95% confidence interval) of MSTNet were 0.92 (0.87‐0.96) for ≥F2 and 0.89 (0.83‐0.95) for F4 on the validation group, which significantly outperformed APRI, FIB‐4 and Forns. The sensitivity and specificity of MSTNet (85.1% (74.5%‐92.0%) and 87.6% (78.0%‐93.6%)) were better than those of three sonographers in assessing ≥F2. Conclusions: The proposed MSTNet is a promising ultrasound image‐based method for the non‐invasive grading of liver fibrosis in patients with chronic HBV infection. [ABSTRACT FROM AUTHOR]

Background: Being a rare disease, cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is easily misdiagnosed as small bowel Crohn's disease (SBCD).Aims: This study was aimed to compare clinical features of CMUSE to SBCD.Methods: Fourteen patients with CMUSE and 61 patients with SBCD were retrospectively analyzed.Results: Hematochezia was more frequent in CMUSE patients (10, 71.4% vs 23, 37.7%, P = 0.022), while diarrhea was more common in SBCD patients (23, 37.7% vs 0, 0.0%, P = 0.015). More patients with CMUSE developed intestinal stenosis than with SBCD (14, 100% vs 37, 60.7%, P = 0.011). 30 (50.0%) SBCD patients and none CMUSE patients had an elevated erythrocyte sedimentation rate level (P = 0.001). Extra-enteric findings found by computed tomography enterography were significantly more prevalent in SBCD patients than in CMUSE patients (25,71.4% vs 3,25%, P = 0.013). Longitudinal ulcers found by endoscopy were more common in SBCD patients (16, 37.2% vs 0, 0.0%, P = 0.041), while circumferential ulcers were more common in CMUSE patients (6, 54.6% vs 8, 18.6%, P = 0.041). All ulcers observed in CMUSE patients were within mucosal and submucosal layers, but 8 (44.4%) SBCD patients had deep ulcers that reached beyond submucosal layers (P = 0.003). Ulcers were located at strictures in 9 (90.0%) CMUSE patients but only in 1 (5.6%) SBCD patient (P = 0.000).Conclusions: Gastrointestinal symptoms, erythrocyte sedimentation rate levels, radiologic, endoscopic and pathologic features help to distinguish CMUSE from SBCD. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC)-related post-colectomy enteritis is a very rare condition that is characterized by diffuse small-bowel mucosal inflammation following colectomy and could be very dangerous. In previously reported cases, corticosteroid therapy seemed to be the optimal choice for inducing remission; however, the patient studied herein presented with severe diarrhoea and hypovolemic shock and failed to achieve full remission with corticosteroid therapy.Case Presentation: We describe the case of a patient with severe pan-enteritis presenting with life-threatening diarrhoea complicated with hypovolemic shock and acute kidney injury after colectomy and ileal pouch anal anastomosis (IPAA) for UC; this patient was successfully treated by ileostomy closure after failing to achieve full remission with corticosteroid therapy. Next, we review other cases of post-colectomy enteritis reported in the literature and propose a flow-chart for its diagnosis and initial treatment.Conclusion: Post-colectomy enteritis can be dangerous, and the early awareness of this condition plays a vital role. Additionally, in patients who do not respond well to corticosteroid or immunosuppressant therapy, early closure of the ileostomy and re-establishment of the natural faecal stream could be important considerations. [ABSTRACT FROM AUTHOR]

Focuses on a study that examined the specific immune responses induced by a multi-epitope antigen of hepatitis C virus in mice and rabbits. Use of GZ-PCX antigens for vaccine; Methodology of the study; Results and discussion; Conclusion.