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Interleukin 10 (IL-10)-producing B cells (B10 cells) are a canonical cell fraction for regulating other activities of immune cells. Posttranscriptional modification of IL-10 in B10 cells is not yet fully understood. Short-chain fatty acids play an important role to regulate the functions of immune cells. This study aims to clarify the role of propionic acid (PA), a short-chain fatty acid, in regulating the expression of IL-10 in B10 cells. Blood samples were collected from patients with food allergy (FA) and healthy subjects. Serum and cellular components were prepared with the samples, and analysed by enzyme-linked immunosorbent assay and flow cytometry, respectively. The results showed that serum PA levels were lower in FA patients. PA concentrations were negatively correlated with serum cytokine Th2 concentrations, specific IgE concentrations in serum and skin prick test results. The peripheral frequency of B10 cells and the production of IL-10 in B cells were also associated with serum PA concentrations. Activation of B cells by CpG induced the production of IL-10 and tristetretrprolin (TTP), in which TTP caused the spontaneous decay of IL-10 mRNA. PA was necessary to stabilize the IL-10 mRNA in B cells by inducing the production of granzyme B, which resulted in the degradation of the IL-10 mRNA. Administration of PA attenuated FA response in mice by maintaining homeostasis of B10 cells. In conclusion, PA is needed to stabilize the expression of IL-10 in B10 cells. PA administration can mitigate experimental FA by maintaining B10 cell functions.

Background: An effective blood-based method for hepatocellular carcinoma (HCC) early detection has not yet been developed. Aberrant DNA methylation may offer opportunities in revolutionizing cancer screening and diagnosis. We sought to identified a non-invasive DNA methylation-based diagnostic approach using cell-free DNA for HCC early detection in high risk population. Methods: Differentially methylated DNA methylation blocks were determined by comparing methylation profiles of biopsy-proven HCC, cirrhotic and healthy liver tissues using targeted bisulfite sequencing. A multi-layer HCC screening model was subsequently constructed based on tissue-derived differentially methylated makers using plasma samples from 120 HCC patients, 92 cirrhotic patients and 290 healthy individuals. This model was independently validated in a cohort consisting of 67 HCC patients, 115 cirrhotic patients and 242 healthy individuals. The clinical parameters of misclassified samples were also investigated. Findings: Based on methylation profiling of tissue samples, a total of 2,321 DNA methylation markers were derived, which were subsequently used to construct a cfDNA-based HCC screening model, achieving a sensitivity of 86% and specificity of 97% in the training cohort and a sensitivity of 82% and specificity of 96% in the independent validation cohort. The HCC screening model can effectively discriminate HCC patients from non-HCC patients, including patients with cirrhosis, HBV infection and healthy individuals, achieving an AUC of 0.956; whereas serum alpha-fetoprotein (AFP) achieved an AUC of 0.803. Interpretation: We have developed and validated an HCC screening model which can effectively distinguish early stage HCC patients from cirrhotic patients and symptomatic HBsAg-seropositive individuals. Funding: Key Research and Development Program of Hunan Province, Natural Science Foundation of Hunan Province, China. Declaration of Interest: None to declare. Ethical Approval: The study was approved by the ethic committee of The Second Xiangya Hospital of Central South University (KYLL2018072) and Chongqing University Cancer Hospital (2019167). All collection and usage of human sample and clinical data were in accordance with the principles of the Declaration of Helsinki. Written informed content was obtained from every participant for the use of their tissue or plasma samples.

To explore the role and mechanism of motilin in colonic motility disorder.A total of 20 male Wistar rats (180 - 200 g) were randomly divided into 2 groups: water avoidance stress (WAS, n = 10) and sham water avoidance stress (SWAS, n = 10). Rats were exposed to 1 h WAS or SWAS daily for 10 consecutive days. Motilin in plasma was measured by enzyme-linked immunosorbent assay (ELISA). Proximal colon circular smooth muscle cells (PCSM) were isolated by enzymatic digestion and L-type calcium currents (ICa(L)) recorded by patch-clamp techniques.The fecal pellets during 1 h WAS significantly increased (5.4 ± 1.0 vs 2.4 ± 0.7, P0.01, n = 10). The motilin in plasma had significant difference between WAS rats and SWAS rats ((135 ± 35) vs (89 ± 24) pg/ml, P0.01, n = 10). The ICa(L) of two rats had no significant difference. But 6 × 10(-5) mmol/L motilin increased ICa(L) more in WAS than in SWAS rats at 0 mV ((1.6 ± 0.4) vs (1.0 ± 0.3) pA/pF, P0.05, n = 10).WAS leads to elevated motilin levels in plasma and active L-type Ca(2+) channels in colon. And it contributes to colonic motility disorder.