G-protein-coupled receptors (GPCR) constitute the largest known superfamily for signal transduction and transmission, and they control a variety of physiological and pathological processes. GPCR adaptor b-arrestins (ARRBs) play a role in cancerous proliferation. However, the effect of ARRBs in inflammation-mediated hepatocellular carcinogenesis is unknown. Here we show that ARRB1, but not ARRB2, is upregulated in inflammation-associated hepatocellular carcinoma (HCC) and paracancerous tissues in humans. A genotoxic carcinogen, diethylnitrosamine (DEN), significantly induces hepatic inflammation, TNF-a production and ARRB1 expression. Although ARRB1 deficiency does not affect hepatic inflammation and TNF-a production, it markedly represses hepatocellular carcinogenesis by suppressing malignant proliferation in DEN-treated mice. Furthermore, TNF-a directly induces hepatic ARRB1 expression and enhances ARRB1 interaction with Akt by binding to boost Akt phosphorylation, resulting in malignant proliferation of liver cells. Our data suggest that ARRB1 enhances hepatocellular carcinogenesis by inflammation-mediated Akt signalling and that ARRB1 may be a potential therapeutic target for HCC.

Sensitive and non-invasive biomarkers for pancreatic cancer (PC) are lacking. We aimed to identify salivary long non-coding RNAs (lncRNAs) as biomarkers in diagnosis of resectable PC. Five well-documented lncRNAs: H19, HOTAIR, HOTTIP, MALAT1, PVT1, which are most closely associated with pancreatic cancer from previous studies were selected as putative lncRNA biomarkers. Their expression in pancreatic tissues and saliva of cancer patients and healthy controls was measured by quantification polymerase chain reaction (qPCR). Compared with benign pancreatic tumour (BPT) and normal pancreatic tissues (NPT), HOTAIR, HOTTIP and PVT1 were significantly up-regulated in pancreatic cancer tissues (PCT). As compared to BPT or healthy groups, the salivary levels of HOTAIR and PVT1 were significantly higher in PC group. They were significantly reduced after the curative pancreatectomy. Both salivary lncRNAs distinguished PC patients from healthy controls and BPT patients with sensitivities and specificities ranging from 60–97%. The expression of salivary HOTAIR and PVT1 did not differ significantly between healthy controls and any one of eight leading cancers worldwide. Collectively, our findings indicate that salivary HOTAIR and PVT1 show potential as novel non-invasive biomarkers for detecting PC.

The synthesis and biodistribution of three triazine dendrimers differing in PEGylation are described. Dendrimers 1, 2, and 3 are derived from a common intermediate, dendrimer 4, and vary in molecular mass from 11 to 73 kDa as a result of PEGylation with multiple (theoretically, 16) PEG groups of 0.6, 2, and 5 kDa, respectively. As expected, elimination half-lives increased with an increase in molecular mass. In light of other results, however, molecular mass proves not to be the primary determinant of elimination half-lives. Instead, these times can be more readily predicted from the number of PEG groups on the dendrimer: the size of the PEG chain contributes to a lesser extent. Tumor uptake is observed for all the three dendrimers in mice bearing prostate cancer xenografts.

Ulcerative colitis is a gastrointestinal disorder intricately associated with intestinal dysbiosis, but effective treatments are currently limited. Indigo naturalis, a traditional Chinese medicine derived from indigo plants, has been widely used in the treatment of ulcerative colitis. However, the specific mechanisms have not yet been identified. Accordingly, in this study, we evaluated the effects and mechanisms of indigo naturalis on dextran sulfate sodium (DSS)-induced colitis in rats. Our results showed that indigo naturalis potently alleviated DSS-induced colitis in rats, and reversed DSS-induced intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing. The protective effects of indigo naturalis were gut microbiota dependent, as demonstrated by antibiotic treatments and fecal microbiota transplantation. Depletion of the gut microbiota through a combination of antibiotic treatments blocked the anti-inflammatory effect of indigo naturalis on the DSS-induced colitis, and the recipients of the gut microbiota from indigo naturalis-treated rats displayed a significantly attenuated intestinal inflammation, which was actively responsive to therapeutic interventions with indigo naturalis. Notably, supplement with indigo naturalis greatly increased the levels of feces butyrate, which was positively correlated with the relative abundances of Ruminococcus_1 and Butyricicoccus. We further showed that indigo naturalis-dependent attenuation of colitis was associated with elevated expression of short-chain fatty acid-associated receptors GPR41 and GPR43. Collectively, these results suggested that indigo naturalis alleviates DSS-induced colitis in rats through a mechanism of the microbiota-butyrate axis, particularly alterations in Ruminococcus_1 and Butyricicoccus abundances, and targetspecific microbial species may have unique therapeutic promise for ulcerative colitis.