IMPORTANCE The gastric cancer (GC)-associated long noncoding RNA1 (lncRNA-GC1) plays an important role in gastric carcinogenesis. However, exosomal lncRNA-GC1 and its potential role in GC are poorly understood. OBJECTIVE To evaluate the diagnostic value of circulating exosomal lncRNA-GC1 for early detection and monitoring progression of GC. DESIGN, SETTING, AND PARTICIPANTS We performed a multiphase investigation of circulating exosomal lncRNA-GC1 for early detection of GC involving consecutive patients with GC (n = 522), patients with gastric precancerous lesions (n = 85), and healthy donor individuals (HDs; n = 219) from December 2016 to February 2019 at Chinese People's Liberation Army General Hospital, China. LncRNA-GC1 was measured by reverse transcription-polymerase chain reaction by independent researchers who had no access to patients' information. Receiver operating characteristic curves were used to calculate diagnostic efficiency in comparison between lncRNA-GC1 and 3 traditional biomarkers (carcinoembryonic antigen [CEA], cancer antigen 72-4 [CA72-4], and CA19-9). MAIN OUTCOMES AND MEASURES Assessment of diagnostic efficiency on the basis of area under curve (AUC), specificity, and sensitivity. RESULTS Of the 826 patients included in the study, 508 were men (61.5%), and the median age of all patients was 60 years (range, 28-82 years). In the test phase, lncRNA-GC1 achieved better diagnostic performance than the standard biomarkers CEA, CA72-4, and CA19-9 (AUC = 0.9033) for distinguishing between the patients with GC and HDs. Additionally, exosomal lncRNA-GC1 levels were significantly higher in culture media from GC cells compared with those of normal gastric epithelial cells (t = 5.310; P = .002). In the verification phase, lncRNA-GC1 retained its diagnostic efficiency in discriminating patients with GC from those with gastric precancerous lesions as well from HDs. Moreover, lncRNA-GC1 exhibited a higher AUC compared with those of CEA, CA72-4, and CA19-9 for early detection of GC with sufficient specificity and sensitivity, especially for patients with GC with negative standard biomarkers. Moreover, the levels of circulating exosomal lncRNA-GC1 were significantly associated with GC from early to advanced stages (HD vs stage I, t = 20.98; P < .001; stage I vs stage II, t = 2.787; P = .006; stage II vs stage III, t = 4.471; P < .001; stage III vs stage IV, t = 1.023; P = .30), independent of pathological grading and Lauren classification (pathological grading: HD vs G1, t = 21.09; P < .001; G1 vs G2, t = 0.3718; P = .71; G2 vs G3, t = 0.3598; P = .72; Lauren classification: t = 24.81; P <.001). In the supplemental phase, the levels of circulating exosomal lncRNA-GC1 were consistent with those in GC tissues and cells and were higher compared with those in normal tissues and cells. Furthermore, the levels of circulating lncRNA-GC1 were unchanged after exosomes were treated with RNase and remained constant after prolonged exposure to room temperature or after repeated freezing and thawing (t = 1.443; P = ....

The present study investigated the preventive effect of polyphenols in Liubao tea (PLT) on carbon tetrachloride (CCl4)-induced liver injury in mice. The mice were initially treated with PLT, followed by induction of liver injury using 10 mL/kg CCl4. Then liver and serum indices, as well as the expression levels of related messenger RNAs (mRNAs) and proteins in liver tissues were measured. The results showed that PLT reduces the liver quality and indices of mice with liver injury. PLT also downregulates aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglycerides (TGs), and malondialdehyde (MDA), and upregulates superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the sera of mice with liver injury. PLT also reduces serum levels of interleukin-6 (IL-6), interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) cytokines in mice with liver injury. Pathological morphological observation also shows that PLT reduces CCl4-induced central venous differentiation of liver tissues and liver cell damage. Furthermore, qPCR and Western blot also confirm that PLT upregulates the mRNA and protein expressions of Gu/Zn-SOD, Mn-SOD, catalase (CAT), GSH-Px, and nuclear factor of κ-light polypeptide gene enhancer in B-cells inhibitor-α (IκB-α) in liver tissues, and downregulates the expression of cyclooxygenase 2 (COX-2) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB). Meanwhile, PLT also raised the phosphorylated (p)-NF-κB p65 and cytochrome P450 reductase protein expression in liver injury mice. The components of PLT include gallic acid, catechin, caffeine, epicatechin (EC), epigallocatechin gallate (EGCG), gallocatechin gallate (GCG), and epicatechin gallate (ECG), which possibly have a wide range of biological activities. Thus, PLT imparts preventive effects against CCl4-induced liver injury, which is similar to silymarin.

Poorly differentiated colorectal cancers (CRCs) are more aggressive and lack targeted therapies. We and others previously reported the predominant role of tumor-suppressor NDRG2 in promoting CRC differentiation, but the underlying mechanism is largely unknown. Herein, we demonstrate that NDRG2 induction of CRC cell differentiation is dependent on the repression of E3 ligase Skp2 activity. In patients and Ndrg2 knockout mice, NDRG2 and Skp2 are negatively correlated and associated with cell differentiation stage. Further, NDRG2 suppression of Skp2 contributes to the inductions and stabilizations of p21 and p27, which are Skp2 target proteins for degradation. The reduction of either p21 or p27 levels by shRNA can decrease NDRG2-induced AKP activity and resume cell growth inhibition, thus both p21 and p27 are required for NDRG2 effect on the promotion of cell differentiation in CRCs. The mechanistic study shows that NDRG2 suppresses β-catenin nuclear translocation and decreases the occupancy of β-catenin/TCF complex on Skp2 promoter, potentially through dephosphorylating GSK-3β. By subjecting a series of NDRG2 deletion mutants to Skp2 expression, the loss of NH2-terminal domain can completely abolish NDRG2-dependent differentiation induction. Supporting the biological significance of the reciprocal relationship between NDRG2 and Skp2, an NDRG2low/Skp2high gene expression signature correlates with poor CRC patient outcome and could be considered as a diagnostic marker of CRCs.

The aim of this study was to investigate and compare the effects of heat-killed and live Lactobacillus on carbon tetrachloride (CCl4)-induced acute liver injury mice. The indexes evaluated included liver pathological changes, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the serum, related gene expression (IL-1β, TNF-α, Bcl-2, and Bax), and related proteins levels (Bax, Bcl-2, Caspase 3, and NF-κB p65). Compared with the model group, the results indicated that the levels of ALT, AST, and MDA in the serum, the expression levels of IL-1β, TNF-α, and Bax, and the protein levels of Bax, Caspase 3, and NF-κB p65 significantly decreased, and the pathologic damage degree all significantly reduced after live Lactobacillus fermentum (L-LF) and live Lactobacillus plantarum (L-LP) treatment. Additionally, the levels of SOD and GSH in the serum, the gene expression of Bcl-2, and the protein level of Bcl-2 significantly increased after L-LF and L-LP treatment. Although HK-LF and HK-LP could also have obvious regulating effects on some of the evaluated indexes (ALT, AST, the expression levels of TNF-α and Bax, and the protein level of Bcl-2) and play an important role in weakening liver damage, the regulating effects of L-LF or L-LP on these indexes were all better compared with the corresponding heat-killed Lactobacillus fermentum (HK-LF) and heat-killed Lactobacillus plantarum (HK-LP). Therefore, these results suggested that LF and LP have an important role in liver disease.

A high-fat diet-induced C57BL/6N mouse model of non-alcoholic fatty liver disease (NAFLD) was established. The effect and mechanism of Raw Bowl Tea polyphenols (RBTP) on preventing NAFLD via regulating intestinal function were observed. The serum, liver, epididymis, small intestine tissues, and feces of mice were examined by biochemical and molecular biological methods, and the composition of RBTP was analyzed by HPLC assay. The results showed that RBTP could effectively reduce the body weight, liver weight, and liver index of NAFLD mice. The serum effects of RBTP were: (1) decreases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), D-lactate (D-LA), diamine oxidase (DAO), lipopolysaccharide (LPS), and an increase of high density lipoprotein cholesterol (HDL-C) levels; (2) a decrease of inflammatory cytokines such as interleukin 1 beta (IL-1β), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α), and interferon gamma (INF-γ); (3) a decrease the reactive oxygen species (ROS) level in liver tissue; and (4) alleviation of pathological injuries of liver, epididymis, and small intestinal tissues caused by NAFLD and protection of body tissues. qPCR and Western blot results showed that RBTP could up-regulate the mRNA and protein expressions of LPL, PPAR-α, CYP7A1, and CPT1, and down-regulate PPAR-γ and C/EBP-α in the liver of NAFLD mice. In addition, RBTP up-regulated the expression of occludin and ZO-1, and down-regulated the expression of CD36 and TNF-α in the small intestines of NAFLD mice. Studies on mice feces showed that RBTP reduced the level of Firmicutes and increased the minimum levels of Bacteroides and Akkermansia, as well as reduced the proportion of Firmicutes/Bacteroides in the feces of NAFLD mice, which play a role in regulating intestinal microecology. Component analysis showed that RBTP contained seven polyphenolic compounds: Gallic acid, (-)-epigallocatechin, catechin, L-epicatechin, (-)-epigallocatechin gallate, (-)-gallocatechin gallate, and (-)-epicatechin gallate (ECG), and high levels of caffeine, (-)-epigallocatechin (EGC), and ECG. RBTP improved the intestinal environment of NAFLD mice with the contained active ingredients, thus playing a role in preventing NAFLD. The effect was positively correlated with the dose of 100 mg/kg, which was even better than that of the clinical drug bezafibrate.