Serotonin, also known as 5-hydroxytryptamine (5-HT) is a signaling mediator that regulates emotion, behavior, and cognition. Previous studies have focused more on the roles of 5-HT in the central nervous system (CNS). However, 5-HT also shares a strong relationship with the pathological cases of tumor, inflammation, and pathogen infection. 5-HT participates in tumor cell migration, metastatic dissemination, and angiogenesis. In addition, 5-HT affects immune regulation via different 5-HT receptors (5-HTRs) expressed immune cells, including both innate and adaptive immune system. Recently, drugs targeting at 5-HT signaling were tested to be beneficial in mouse models and clinical trials of multiple sclerosis (MS) and inflammatory bowel disease (IBD). Thus, it is reasonable to assume that 5-HT participates in the pathogenesis of autoimmune diseases. However, the underlying mechanism by 5-HT modulates the development of autoimmune diseases has not been fully understood. Based on our previous studies and pertinent literature, we provide circumstantial evidence for an essential role of 5-HT, especially the regulation of 5-HT on immune cells in the pathogenesis of autoimmune diseases, which may provide a new point cut for the treatment of autoimmune diseases.

The objective of the present study was to explore the common and specific metabolic alterations of hepatocellular carcinoma (HCC) infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). Serum profiling data revealed that the two HCC groups shared a mainly similar metabolic profile, providing a basis for investigating their common tumor pathogenesis mechanism and early diagnosis biomarkers. Arachidonic acid as a pro-inflammatory precursor increased significantly in the HCC group compared to the cirrhosis and healthy control. And the lysophosphatidylcholines (lysoPCs) with polyunsaturated fatty acid acyl chain with potent anti-inflammatory activity significantly decreased in the HCC and cirrhosis groups compared to those in the healthy control group, which may partly contribute to maintaining chronic inflammation and benefit the initiation and progression of the malignant hepatic tumor. The decreased ratios of polyunsaturated lysoPCs to saturated lysoPCs in HCC groups compared to chronic liver diseases infected with HBV or HCV and healthy control further demonstrated that a malignant liver tumor exerts profound influences independent of virus infection. Especially, serum endocannabinoids anandamide (AEA) and palmitylethanolamide (PEA) were found significantly elevated in HCC groups compared to healthy control, and in HCC with HCV compared to corresponding chronic liver diseases. AEA, PEA, or their combination showed better sensitivity, specificity, and the area under the curve for distinguishing HCC from chronic liver diseases, showing they are potential biomarkers to distinguish the HCC from cirrhosis infected with HCV.

Hepatitis B virus (HBV) can cause chronic hepatitis B, which may lead to cirrhosis and liver cancer. Type I interferon (IFN) is an approved drug for the treatment of chronic hepatitis B. However, the fundamental mechanisms of antiviral action by type I IFN and the downstream signaling pathway are unclear. TRIM25 is an IFN-stimulated gene (ISG) that has an important role in RIG-I ubiquitination and activation. Whether TRIM25 is induced in liver cells by type I IFN to mediate anti-HBV function remains unclear. Here we report that interleukin-27 (IL-27) has a critical role in IFN-induced TRIM25 upregulation. TRIM25 induction requires both STAT1 and STAT3. In TRIM25 knockout HepG2 cells, type I IFN production was consistently attenuated and HBV replication was increased, whereas overexpression of TRIM25 in HepG2 cells resulted in elevated IFN production and reduced HBV replication. More interestingly, we found that TRIM25 expression was downregulated in HBV patients and the addition of serum samples from HBV patients could inhibit TRIM25 expression in HepG2 cells, suggesting that HBV might have involved a mechanism to inhibit antiviral ISG expression and induce IFN resistance. Collectively, our results demonstrate that type I IFN -induced TRIM25 is an important factor in inhibiting HBV replication, and the IFN-IL-27-TRIM25 axis may represent a new target for treating HBV infection.

The occurrence of hepatocellular carcinoma (HCC) is two to three times higher in patients with diabetes mellitus (DM), the prevalence of which is increasing sharply worldwide. The purpose of this review was to describe clinical links between DM and HCC and potential biological mechanisms that may account for this association. We evaluated the role of potential pathways that could account for the development of HCC with different etiologies in the presence of DM. In addition, we also briefly discuss the potential effect of other factors such as type and dosage of antidiabetic medicines and duration of DM on HCC risk.

Active UC is characterized by exhaustion of regulatory control in the B cell compartment.