Helicobacter pylori causes gastritis, which has been attributed to the development of H. pylori–specific T cells during infection. However, the mechanism underlying innate immune detection leading to the priming of T cells is not fully understood, as H. pylori evades TLR detection. Here, we report that H. pylori metabolites modified from host cholesterol exacerbate gastritis through the interaction with C-type lectin receptors. Cholesteryl acyl α-glucoside (αCAG) and cholesteryl phosphatidyl α-glucoside (αCPG) were identified as noncanonical ligands for Mincle (Clec4e) and DCAR (Clec4b1). During chronic infection, H. pylori–specific T cell responses and gastritis were ameliorated in Mincle-deficient mice, although bacterial burdens remained unchanged. Furthermore, a mutant H. pylori strain lacking αCAG and αCPG exhibited an impaired ability to cause gastritis. Thus H. pylori–specific modification of host cholesterol plays a pathophysiological role that exacerbates gastric inflammation by triggering C-type lectin receptors.

Accumulating evidence indicates that cell death triggers sterile inflammation and that impaired clearance of dead cells causes nonresolving inflammation; however, the underlying mechanisms are still unclear. Here, we show that macrophage-inducible C-type lectin (Mincle) senses renal tubular cell death to induce sustained inflammation after acute kidney injury in mice. Mincle-deficient mice were protected against tissue damage and subsequent atrophy of the kidney after ischemia–reperfusion injury. Using lipophilic extract from the injured kidney, we identified β-glucosylceramide as an endogenous Mincle ligand. Notably, free cholesterol markedly enhanced the agonistic effect of β-glucosylceramide on Mincle. Moreover, β-glucosylceramide and free cholesterol accumulated in dead renal tubules in proximity to Mincle-expressing macrophages, where Mincle was supposed to inhibit clearance of dead cells and increase proinflammatory cytokine production. This study demonstrates that β-glucosylceramide in combination with free cholesterol acts on Mincle as an endogenous ligand to induce cell death–triggered, sustained inflammation after acute kidney injury.

Mastic gum is derived from the tree named Pistacia lentiscus that is grown only in Island Hios of Greek. Since Mastic was first reported to kill Helicobacter pylori (H. pylori) in 1998, there has been no further study to elucidate which component of mastic specifically shows the antimicrobial activity against H. pylori. In this study, we examined which component of mastic gum was responsible for anti-H. pylori activity. We prepared the essential oil of mastic gum and identified 20 constituents by GC–MS analysis. Ten standard components were assayed for anti-H. pylori activity, and it clarified that α-terpineol and (E)-methyl isoeugenol showed the anti-H. pylori activity against four different H. pylori strains that were established from patients with gastritis, gastric ulcer and gastric cancer. These components could be useful to overcome the drug-resistance H. pylori growth in stomach. Graphical Abstract

Okinawa mozuku (Cladosiphon okamuranus Tokida) is an edible seaweed classified as brown algae and is a native species of the Ryukyu Islands in Japan. In recent years, the genomic decoding of Okinawa mozuku has been completed. Previous studies on the anti-inflammatory, antiviral, and antitumor properties of Okinawa mozuku have suggested that it affects the regulation of cellular and humoral immunity. The aim of the present study was to examine the immunoregulatory effect of fucoidan derived from Okinawa mozuku in mice. A product containing fucoidan (purity, 88.3%; molecular weight, 49.8 kDa) was developed from Okinawa mozuku and tested for its immunoregulatory effects in mice. The experimental animals were 8-week-old female BALB/c mice to which fucoidan (0, 102.5, 205.0, 410.0, and 1025.0 mg/kg) was administered orally continuously for six weeks. Immune cell proliferation, cytokine production, macrophage phagocytosis, and serum antibody concentration were measured. We found that immune cell proliferation, interleukin (IL)-2, macrophage phagocytes, and serum antibodies (IgM, -G, -A) increased significantly, but IL-4, -5, and IgE decreased significantly. These results indicated that fucoidan modulated cellular and humoral immunity.

Cis-Hinokiresinol (CHR) is a norlignan constituent from Anemarrhena asphodeloides BUNGE (Liliaceae), which shows hyaluronidase inhibitory activity. In the present studies, we have demonstrated that CHR selectively inhibited endothelial cell proliferation compared with cancer cells, and especially basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation. Furthermore, endothelial cell migration and tube formation, two important steps in the angiogenic process, were also inhibited by CHR. Moreover, CHR reduced the vessel growth induced by VEGF in the mouse corneal neovascularization model. These results suggest that CHR may prove useful for the development of a novel angiogenesis inhibitor.

Four new cembrane diterpenes (1—4) and fifteen known cembranoids (5—19) were isolated from an Okinawan soft coral Lobophytum crassum. The structures of these four new cembranoids were determined on the basis of spectroscopic evidence. In particular, the absolute stereochemistry of 1, 2, 5 and 6 were elucidated by the application of the modified Mosher's method and circular dichroism (CD) spectral data. The inhibitory effects of some isolates were evaluated on nitric oxide (NO) production against a murine macrophage-like cell line (Raw 264.7). Cembranoids consisting of α-methylene-γ-lactone, exhibited the significant effect on NO production.