No abstract

BackgroundLong non-coding RNAs (lncRNAs) show great potential as diagnostic tools in many diseases. We aimed to develop sensitive and noninvasive biomarkers in saliva for detecting early hepatocellular carcinoma (HCC).MethodsCandidate lncRNA biomarkers identified by Agilent microarray were subjected to validation using qPCR for the quantification of their expression levels in independent tissue, plasma and saliva sample sets, including healthy controls, HBsAg carriers, patients with chronic Hepatitis B, liver cirrhosis, early HCC, and advanced HCC. Levels of candidate biomarkers were also measured in totally 108 saliva samples from patients with any one of other nine leading causes of cancer death in men and women.FindingsLnc-PCDH9-13:1 was significantly elevated in HCC tissues, plasma and saliva of HCC patients compared with healthy controls and groups of several benign liver diseases and other leading cancers. Its level was significantly reduced after curative hepatectomy but significantly elevated again if HCC recurrence occurred. Salivary lnc-PCDH9-13:1 showed reasonable specificities and sensitivities for detecting HCC compared with several control groups. Furthermore, the overexpression of lnc-PCDH9-13:1 promotes cell proliferation and migration in vitro.InterpretationSalivary lnc-PCDH9-13:1 is a desirable biomarker for early HCC. It may help warrant prospective validation with larger sample sizes in multi-centers.

Background and Aims: Liver fibrosis is a chronic disease characterized by different etiological agents; dysregulated interactions between hepatocytes and HSCs contribute to this disease. β-arrestin 1 (ARRB1) plays an important role in liver fibrosis; however, the effect of ARRB1 on the crosstalk between hepatocytes and HSCs in liver fibrosis is unknown. The aim of this study is to investigate how ARRB1 modulates hepatocyte and HSC activation during liver fibrosis.Approach and Results: Normal and fibrotic human liver and serum samples were obtained. CCl 4 -induced liver fibrosis and methionine-choline deficiencyinduced NASH models were constructed. Primary hepatocytes and HSCs were isolated, and human hepatic LO2 and stellate LX2 cells were used. Small extracellular vesicles (EVs) were purified, and key proteins were identified.ARRB1 was up-regulated in hepatocytes and associated with autophagic blockage in liver fibrosis. ARRB1 increased the release of hepatocyte-derived small EVs by inhibiting multivesicular body lysosomal degradation and activating Rab27A, thereby activating HSCs. Proteomic analyses showed that mannanbinding lectin serine protease 1 (MASP1) was enriched in hepatocyte-derived small EVs and activated HSCs via p38 mitogen-activated protein kinase (MAPK)/ activating transcription factor 2 (ATF2) signaling. ARRB1 up-regulated MASP1 expression in hepatocytes. MASP1 promoted liver fibrosis in mice. Clinically, MASP1 expression was increased in the serum and liver tissue of patients with liver fibrosis.Conclusions: ARRB1 up-regulates the release of hepatocyte-derived MASP1enriched small EVs by regulating the autophagic-lysosomal/multivesicular body

These results suggest that hABH2 is downregulated in a subset of gastric cancers, and might be involved in the molecular mechanism of gastric cancer through inhibiting the proliferation of gastric cancer cells.

Fine varieties of the Yunwu Tribute Tea (Camellia Sinensis (L.) Kuntze var. niaowangensis Q. H. Chen) are distributed on the Yunwu Mountain, Guiding County, Guizhou province, China. Cold stress usually occurs in winter and is one of the most significant environmental factors restricting the growth of this plant as well as its geographical distribution. However, only few systematic studies have examined the molecular mechanism of cold tolerance in the Yunwu Tribute Tea. Hence, in this study, Illumina HiSeq technology was applied to investigate the cold-tolerance mechanism and for this purpose, cDNA libraries were obtained from two groups of samples namely, the cold-treated group (DW) and the control group (CK). A total of 185,973 unigenes were produced from 511,987 assembled transcripts and among these, 16,020 differentially expressed genes (DEGs) (corrected p-value <0.01, |log2(fold change)| >3), including 9,606 upregulated and 6,414 downregulated genes, were obtained. Moreover, the antioxidant enzyme system, plant hormone signal transduction, proline metabolism, tyrosine metabolism pathway, and transcription factors were analyzed and based on the results, a series of candidate genes related to cold stress were screened out and discussed. The physiological indexes related to the low temperature response were tested, along with five DEGs which were validated by quantitative real-time PCR. For this study, it is expected that the results of the transcriptome sequence of Yunwu Tribute Tea will provide valuable clues for genetic studies while helping to screen candidate genes for cold-resistance breeding in tea plants.