Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular rate-limiting enzyme in the metabolism of tryptophan along the kynurenine pathway, subsequently mediating the immune response; however, the role of IDO1 in liver fibrosis and cirrhosis is still unclear. In this study, we investigated the role of IDO1 in the development of hepatic fibrosis and cirrhosis. Patients with hepatitis B virus-induced cirrhosis and healthy volunteers were enrolled. For animals, carbon tetrachloride (CCl4) was used to establish liver fibrosis in wild-type and IDO1 knockout mice. Additionally, an IDO1 inhibitor (1-methyl-D-tryptophan) was administered to WT fibrosis mice. Liver lesions were positively correlated with serum IDO1 levels in both the clinical subjects and hepatic fibrosis mice. A positive correlation between serum IDO1 levels and liver stiffness values was found in the cirrhosis patients. Notably, IDO1 knockout mice were protected from CCl4-induced liver fibrosis, as reflected by unchanged serum alanine transaminase and aspartate transaminase levels and lower collagen deposition, α-smooth muscle actin expression and apoptotic cell death rates. On the other hand, tryptophan 2,3-dioxygenase (TDO), another systemic tryptophan metabolism enzyme, exhibited a compensatory increase as a result of IDO1 deficiency. Moreover, hepatic interleukin-17a, a characteristic cytokine of T helper 17 (Th17) cells, and downstream cytokines’ mRNA levels showed lower expression in the IDO1–/– model mice. IDO1 appears to be a potential hallmark of liver lesions, and its deficiency protects mice from CCl4-induced fibrosis mediated by Th17 cells down-regulation and TDO compensation.

Nanospherical lithium titanium oxide (LTO; Li4Ti5O12) is doped with calcium by a novel route. The prepared material displays superior rate performance prepared with an ultrahigh specific capacity of 155.1 mAh g−1 at 10 C after 1000 cycles. Using density functional theory (DFT) calculations, it is also revealed that the energetically favorable substitution of calcium on the lithium sites in LTO spinel induces a conversion in the electrical conductivity behavior, from intrinsic insulator to metallic, which accounts for the good rate performance. The strategy of combining calcium doping with nanostructuring provides a potentially rewarding avenue towards the design and optimization of common electrode materials.

One new 3,24-dinor-2,4-seco-ursane triterpene, rosanortriterpene C (1), together with four known compounds including 24-norursane-type nortriterpenes (2-3), 24-noroleanane-type nortriterpene (4), ursanetype triterpene (5), was isolated from the fruits of Rosa laevigata var. leiocapus. The new structure was elucidated through comprehensive spectroscopic analysis, including one dimensional (1D) and 2D NMR data, as well as electrospray ionization high resolution (HR-ESI) MS and IR spectrometry. Compounds 1-5 showed moderate anti-inflammatory activities against the production of nitric oxide (NO) in RAW264.7 cells stimulated by lipopolysaccharide (LPS) with IC 50 values of 10.35 0.92, 14.28 1.20, 5.04 1.43, 29.29 3.64, and 14.37 0.59 µM, respectively.

Three new dimeric kavalactones, designated as diyangonins A-C (1-3), along with two known analogs were isolated from the roots of Piper methysticum. Their structures were elucidated by means of extensive analysis of their 1D, 2D NMR, and mass spectroscopic data. All these dimers possess a skeleton featuring a cyclobutane ring connecting two kavalactone units in head-to-tail or head-to-head mode. Compounds 1-5 were evaluated for their cytotoxic activities against human tumor cell lines.

Radiation enteritis is a common side effect of radiotherapy for abdominal and pelvic malignancies, which can lead to a decrease in patients’ tolerance to radiotherapy and the quality of life. It has been demonstrated that glycyrrhizin (GL) possesses significant anti-inflammatory activity. However, little is known about its anti-inflammatory effect in radiation enteritis. In the present study, we aimed to investigate the potential anti-inflammatory effects of GL on radiation enteritis and elucidate the possible underlying molecular mechanisms involved. The C57BL/6 mice were subjected to 6.5 Gy abdominal X-ray irradiation to establish a model of radiation enteritis. Hematoxylin and eosin staining was performed to analyze the pathological changes in the jejunum. The expression of TNF-α in the jejunum was analyzed by immunochemistry. The levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1β, and HMGB1 in the serum were determined by enzyme-linked immunosorbent assay. The intestinal absorption capacity was tested using the D-xylose absorption assay. The levels of HMGB1 and TLR4 were analyzed by western blotting and immunofluorescence staining. We found that GL significantly alleviated the intestinal damage and reduced the levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1β, and HMGB1 levels. Furthermore, the HMGB1/TLR4 signaling pathway was significantly downregulated by GL treatment. In conclusion, these findings indicate that GL has a protective effect against radiation enteritis through the inhibition of the intestinal damage and the inflammatory responses, as well as the HMGB1/TLR4 signaling pathway. Thereby, GL might be a potential therapeutic agent for the treatment of radiation enteritis.