Acute oxidative stress induced by ischemia-reperfusion or inflammation causes serious damage to tissues, and persistent oxidative stress is accepted as one of the causes of many common diseases including cancer. We show here that hydrogen (H(2)) has potential as an antioxidant in preventive and therapeutic applications. We induced acute oxidative stress in cultured cells by three independent methods. H(2) selectively reduced the hydroxyl radical, the most cytotoxic of reactive oxygen species (ROS), and effectively protected cells; however, H(2) did not react with other ROS, which possess physiological roles. We used an acute rat model in which oxidative stress damage was induced in the brain by focal ischemia and reperfusion. The inhalation of H(2) gas markedly suppressed brain injury by buffering the effects of oxidative stress. Thus H(2) can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage.

ObjectiveTo gain insights into the virulence suppressive mechanism of a nonpathogenic strain of Rhizobium vitis ARK-1, we co-inoculated ARK-1 with a tumorigenic (Ti) strain of R. vitis to examine the expression of two essential virulence genes (virA and virG) and one non-essential gene (virD3) of the Ti strain at the wound site of grapevine.ResultsCo-inoculation of ARK-1 with a Ti strain VAT03-9 at a 1:1 cell ratio into grapevine shoots resulted in significantly lower expression of the virulence genes virA, virD3, and virG of VAT03-9 at 1 day after inoculation compared with those when shoots were inoculated only with VAT03-9. ARK-1 was not able to catabolize acetosyringone, which is the plant-derived metabolites inducing the entire vir regulon in Ti strains, suggesting the direct effect of ARK-1 on the induction of broad range of vir genes of R. vitis Ti strains.Electronic supplementary materialThe online version of this article (10.1186/s13104-018-4038-6) contains supplementary material, which is available to authorized users.

Summary Rhizoctonia solani is a soil‐borne fungus causing sheath blight. In consistent with its necrotrophic life style, no rice cultivars fully resistant to R. solani are known, and agrochemical plant defense activators used for rice blast, which upregulate a phytohormonal salicylic acid (SA)‐dependent pathway, are ineffective towards this pathogen. As a result of the unavailability of genetics, the infection process of R. solani remains unclear.We used the model monocotyledonous plants Brachypodium distachyon and rice, and evaluated the effects of phytohormone‐induced resistance to R. solani by pharmacological, genetic and microscopic approaches to understand fungal pathogenicity.Pretreatment with SA, but not with plant defense activators used in agriculture, can unexpectedly induce sheath blight resistance in plants. SA treatment inhibits the advancement of R. solani to the point in the infection process in which fungal biomass shows remarkable expansion and specific infection machinery is developed. The involvement of SA in R. solani resistance is demonstrated by SA‐deficient NahG transgenic rice and the sheath blight‐resistant B. distachyon accessions, Bd3‐1 and Gaz‐4, which activate SA‐dependent signaling on inoculation.Our findings suggest a hemi‐biotrophic nature of R. solani, which can be targeted by SA‐dependent plant immunity. Furthermore, B. distachyon provides a genetic resource that can confer disease resistance against R. solani to plants.

BackgroundThe peritoneum is one of the most frequent metastatic sites in pancreatic cancer patients, and peritoneal dissemination makes this disease refractory due to aggressive progression and chemoresistance. Although the role of the tumor microenvironment in cancer development is recognized, the correlation between the peritoneal environment and refractoriness of peritoneal dissemination remains unclear. The intraperitoneal tumor-microenvironment and its potential role in the progression of peritoneal dissemination and chemo-refractoriness, focusing especially on macrophages, were investigated.Materials and methodsPeritoneal washes were obtained from pancreatic cancer patients, and cellular components were subjected to immunofluorescence assays. The effects of macrophages induced from monocytic THP-1 cells on pancreatic cancer cells were examined in co-culture conditions. The in vivo effects of macrophages on tumor growth and chemo-sensitivity were investigated by subcutaneously or intraperitoneally co-injecting cancer cells with macrophages into mice.ResultsCD204-positive macrophages were present along with cancer cells in the peritoneal washes. In in vitro co-culture, tumor-associated macrophages affected pancreatic cancer cells, induced the epithelial-to-mesenchymal transition (EMT), and made them more resistant to chemotherapeutic agents. M2 macrophages promoted growth of both subcutaneous tumors and peritoneal dissemination in mice. Furthermore, co-inoculation of M2 macrophages conferred chemoresistance in the peritoneal dissemination mouse model, which significantly shortened their survival.ConclusionIntraperitoneal tumor-associated macrophages potentially play an important role in promotion of peritoneal dissemination and chemoresistance of pancreatic cancer via EMT induction.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0981-2) contains supplementary material, which is available to authorized users.

Objective. Peroxisome proliferator-activated receptor ␥ (PPAR␥) is a member of the nuclear hormone receptor superfamily and functions as a key regulator of lipid and glucose metabolism, atherosclerosis, and inflammatory responses. This study was undertaken to evaluate the biologic role of PPAR␥ in self-limiting episodes of acute gouty arthritis. To do this, we investigated PPAR␥ expression by monosodium urate monohydrate (MSU) crystal-stimulated monocytes, and we studied the effects of PPAR␥ ligands on crystal-induced acute inflammation.Methods. PPAR␥ expression by MSU crystalstimulated human peripheral blood mononuclear cells was determined by reverse transcription-polymerase chain reaction and immunostaining. Expression of CD36 on monocytes was detected by flow cytometric analysis. The effects of PPAR␥ ligands on in vitro crystal-induced cytokine production and on in vivo cellular infiltration during crystal-induced acute inflammation were also investigated.Results. MSU crystals rapidly and selectively induced PPAR␥ expression by monocytes. Gene expression was detected as early as 2 hours, and maximum expression was observed at 4 hours after stimulation. The induced PPAR␥ was functional, since a PPAR␥ ligand was able to up-regulate CD36 expression on monocytes. A natural ligand of PPAR␥, 15-deoxy-⌬ 12,14 -prostaglandin J 2 (15deoxy-PGJ 2 ), significantly reduced the crystal-induced production of cytokines by monocytes. Indomethacin inhibited cytokine production only at high concentrations, and an antidiabetic thiazolidinedione (troglitazone) failed to exert significant effects. Administration of troglitazone and 15deoxy-PGJ 2 significantly prevented cellular accumulation in a mouse air-pouch model of MSU crystal-induced acute inflammation.Conclusion. Rapid induction of PPAR␥ expression on monocytes by MSU crystals may contribute, at least in part, to the spontaneous resolution of acute attacks of gout.