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IntroductionImmune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown. MethodsWe investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs).ResultsThe genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs.DiscussionOur Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy.

Additional file 1: Table S1. ICD-10 codes for diagnosis. Table S2. Definitions of levels of smoking, diabetes mellitus, hypertension, and dyslipidemia used in this study. Table S3. Impact of LDL-cholesterol level on sudden cardiac arrest and age-divided subgroup analysis.

Additional file 1: Supplemental Figure S1. Non-alcoholic fatty liver disease activity score. Prebiotic inulin supplementation prevents NAFLD/NASH development. Mice were fed a low-fat/fructose/cholesterol diet (LFC), a high-fat/fructose/cholesterol diet (HFC) or a 10% (w/w) inulin-supplemented HFC diet (HFC+IN) for 20 weeks. Data are mean ± SEM. *P

Natural products with non-toxic and environmentally friendly properties are good sources for skin-whitening and brightening cosmetic agents. Strawberries (Fragaria ananassa), and their parts are used as cosmetic agents, because they contain high levels of bioactive substances. We isolated and identified compounds from F. ananassa calyx. Oleanolic acid has multiple biological activities, including anti-tumor, anti-angiogenic, antiinflammatory, anti-oxidant, and pro-apoptotic effects. However, no study has investigated the influence of oleanolic acid on melanin synthesis in B16-F10 melanoma cells. In the present study, we investigated the effect of oleanolic acid on melanin biosynthesis in B16-F10 melanoma cells stimulated with α-melanocyte stimulating hormone (α-MSH). Oleanolic acid-mediated melanogenesis inhibition was studied by measuring intracellular and secreted melanin levels and by using Western blot and semiquantitative reverse transcriptase-polymerase chain reaction analyses. Oleanolic acid suppressed melanin release and expression, resulting in a significant dose-dependent decrease in secreted and intracellular melanin levels and cellular tyrosinase activity. Furthermore, it inhibited the expression of melanogenesis-associated factors, including tyrosinase, tyrosinase-related proteins-1 and -2, and microphthalmia-associated transcription factor, in α-MSH-stimulated B16-F10 melanoma cells. The results of the present study can contribute to the development of cosmetic agents utilizing the skin whitening and brightening effect of oleanolic acid, which will likely have a wide range of applications in the cosmetic industry and/or clinical practice in the future.

Nod2 belongs to the (NOD)-like receptor (NLR) family of proteins, which function as intracellular pathogen sensors in innate immune cells. Nod2-deficiency results in an impaired immune response against bacterial pathogens. However, our understanding of how this protein promotes host defense against intracellular parasites is unknown. Here we found that Nod2−/− mice showed reduced clearance of Toxoplasma gondii and decreased interferon-γ production. Reconstitution of T-cell deficient mice with Nod2−/− T cells followed by T. gondii infection revealed a T cell-intrinsic defect. Nod2−/− CD4+ T cells displayed poor helper T cell differentiation, which was associated with impaired IL-2 production and nuclear accumulation of c-Rel. These data revealed a T cell-intrinsic role of Nod2 signaling that is critical for host defense against T. gondii.

Purpose Methods and Materials Results Conclusion References Personal Information, Purpose: To compare the usefulness of STIR-FLAIR (short tau inversion recovery-fluid attenuated inversion recovery) images with T2 weighted MR images and STIR (short tau inversion recovery) in diagnosis of multiple...

Nod2 is an intracellular innate immune receptor that plays a role in host defense and susceptibility to inflammatory disease. We show in this study that macrophages rendered refractory to TLR4 and Nod2 signaling by exposure to LPS and muramyl dipeptide (MDP) exhibit impaired TNF-alpha and IL-6 production in response to pathogenic Listeria monocytogenes and Yersinia pseudotuberculosis as well as commensal bacteria including Escherichia coli and Bacteroides fragilis. Surprisingly, Nod2 deficiency was associated with impaired tolerization in response to pathogenic and commensal bacteria. Mechanistically, reduced tolerization of Nod2-null macrophages was mediated by recognition of bacteria through Nod1 because it was abolished in macrophages deficient in Nod1 and Nod2. Consistently, Nod2-null macrophages tolerant to LPS and MDP showed enhanced production of TNF-alpha and IL-6 as well as increased NF-kappaB and MAPK activation in response to the dipeptide KF1B, the Nod1 agonist. Furthermore, reduced tolerization of Nod2-deficient macrophages in response to bacteria was abolished when mutant macrophages were also rendered tolerant to the Nod1 ligand. Finally, MDP stimulation induced refractoriness not only to MDP, but also to iE-DAP stimulation, providing a mechanism to explain the reduced tolerization of Nod2-deficient macrophages infected with bacteria. These results demonstrate that cross-tolerization between Nod1 and Nod2 leads to increase recognition of both pathogenic and commensal bacteria in Nod2-deficient macrophages pre-exposed to microbial ligands.