Interleukin-10 in the Pathophysiology of Inflammatory Bowel Disease: Increased Serum Concentrations During the Recovery Phase

Using a specific enzyme-linked immunosorbent assay, IL-10 concentrations were measured in serum from 62 patients with ulcerative colitis (UC), 43 with Crohn's disease (CD), 25 with other colitides, and 44 normal control subjects. Serum IL-10 concentrations were increased in patients with active UC but not in those with active CD when compared with normal control subjects. A time course study showed that in patients with UC and CD, serum concentrations of IL-6 and C-reactive protein increased during the acute phase and returned to normal as patients go into remission. Notably, serum IL-10 concentrations increased during the phase of disease resolution and declined thereafter regardless of the treatment modality. Gel filtration analysis indicated that IL-10 circulated predominantly as a dimer. In conclusion, this study shows that serum IL-10 is increased during disease recovery in patients with inflammatory bowel disease, and may be a helpful marker in monitoring disease status

Proteolytic Processing of Stat6 Signaling in Mast Cells as a Negative Regulatory Mechanism

Accumulating evidence has shown the importance of Stat6-mediated signaling in allergic diseases. In this study, we show a novel regulatory mechanism of Stat6-mediated signaling in mast cells. When Stat6 is activated by interleukin (IL)-4 and translocated to the nucleus, Stat6 is cleaved by a nucleus-associated protease in mast cells. The cleaved 65-kD Stat6 lacks the COOH-terminal transactivation domain and functions as a dominant-negative molecule to Stat6-mediated transcription. The retrovirus-mediated expression of cleavage-resistant Stat6 mutants prolongs the nuclear accumulation of Stat6 upon IL-4 stimulation and enhances IL-4–induced gene expression and growth inhibition in mast cells. These results indicate that the proteolytic processing of Stat6 functions as a lineage-specific negative regulator of Stat6-dependent signaling in mast cells, and thus suggest that it may account for the limited role of Stat6 in IL-4 signaling in mast cells

Targeted delivery using membrane vesicles in prokaryotes

publishe

Percutaneous Radiofrequency Ablation with or without Chemolipiodolization for Hepatocellular Carcinoma: A Propensity-Score-Matched Analysis

Chemolipiodolization (CL) is less invasive than transarterial chemoembolization (TACE) for managing hepatocellular carcinoma (HCC) because it helps avoid embolization. However, the treatment outcomes of percutaneous radiofrequency ablation (PRFA) with or without CL for HCC remain unclear. Herein, we compared the prognostic factors for overall survival (OS) following PRFA with or without CL for HCC using propensity-score-matched analysis. A total of 221 patients with HCC treated with PRFA at Saga Central Hospital between April 2004 and October 2020, with or without CL, were enrolled. No significant difference was observed in OS between PRFA with and without CL cohorts (median survival time (MST): 4.5 vs. 5.4 years; p = 0.0806). To reduce the confounding effects of 12 variables, we performed propensity-score-matched analysis to match patients treated with PRFA with or without CL. No significant difference was observed in OS between PRFA with and without CL cohorts (MST: 4.0 vs. 3.6 years; p = 0.5474). After stratification according to tumor size, no significant difference was observed in OS for patients with tumor size ≥20 mm between PRFA with and without CL cohorts (MST: 3.5 vs. 3.4 years; p = 0.8236). PRFA with CL was not a significant prognostic factor in both univariate and multivariate analyses (p = 0.5477 and 0.9600, respectively). Our findings suggest that PRFA with CL does not demonstrate more favorable prognosis than PRFA without CL for HCC, regardless of tumor size

Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis

潰瘍性大腸炎による上皮再構築メカニズムと発がんとの関係を解明 --IL-17シグナル経路に変異を獲得した上皮細胞は発がん過程で陰性に選択される--. 京都大学プレスリリース. 2019-12-20.Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer1, 2, 3. However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGR and HNRNPF genes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals. Mutational profiles vary substantially between colitis-associated cancer and non-dysplastic tissues in ulcerative colitis, which indicates that there are distinct mechanisms of positive selection in both tissues. In particular, mutations in NFKBIZ are highly prevalent in the epithelium of patients with ulcerative colitis but rarely found in both sporadic and colitis-associated cancer, indicating that NFKBIZ-mutant cells are selected against during colorectal carcinogenesis. In further support of this negative selection, we found that tumour formation was significantly attenuated in Nfkbiz-mutant mice and cell competition was compromised by disruption of NFKBIZ in human colorectal cancer cells. Our results highlight common and discrete mechanisms of clonal selection in inflammatory tissues, which reveal unexpected cancer vulnerabilities that could potentially be exploited for therapeutics in colorectal cancer

A deeper semantic role for the mirror system

Below are links to the 15 supplemental commentaries on the target article, "From monkey-like action recognition to human language: An evolutionary framework for neurolinguistics " by Michael A. Arbib