The results indicate that triflavin effectively prevents thrombocytopenia, possibly through the following 2 mechanisms: (1) Triflavin markedly inhibits platelet aggregation, resulting in decreased thromboxane A2 formation. (2) It inhibits the adhesion of platelets to subendothelial matrixes, thereby leading to a reversal in the distribution of platelets in blood and liver in LPS-treated rats.

Immunotherapies have shown promising results in certain cancer patients. For hepatocellular carcinoma (HCC), the multiplicity of an immunotolerant microenvironment within both the tumor, and the liver per se may limit the efficacy of cancer immunotherapies. Since radiation induces immunogenic cell death and inflammatory reactions within the tumor microenvironment, we hypothesized that a combination therapy of radiation and lasting local immunostimulating agents, achieved by intratumoral injection of an adenoviral vector encoding interleukin 12, may reverse the immunotolerant microenvironment within a well-established orthotopic HCC toward a state favorable for inducing antitumor immunities. Our data showed that radiation and IL-12 combination therapy (RT/IL-12) led to dramatic tumor regression in animals bearing large subcutaneous or orthotopic HCC, induced systemic effect against distant tumor, and significantly prolonged survival. Radiation monotherapy induced tumor regression at early times but afterwards most tumors regained exponential growth, while IL-12 monotherapy only delayed tumor growth. Mechanistic studies revealed that RT/IL-12 increased expression of MHC class II and co-stimulatory molecules CD40 and CD86 on tumor-infiltrating dendritic cells, suggesting an improvement of their antigen presentation activity. RT/IL-12 also significantly reduced accumulation of tumor-infiltrating myeloid-derived suppressor cells (MDSCs) and impaired their suppressive functions by reducing production of reactive oxygen species. Accordingly, tumor-infiltrating CD8+ T cells and NK cells were significantly activated toward the antitumor phenotype, as revealed by increased expression of CD107a and TNF-α. Together, our data showed that RT/IL-12 treatment could reset the intratumoral immunotolerant state and stimulate activation of antitumor cellular immunity that is capable of eliminating large established HCC tumors.

Our results have mechanical implications for prenatal imprinting of atopy and shed light on the importance of fetal phagocytes in shaping the developing immune system and initiating allergic airway diseases.

No abstract

d-Serine is an amino acid and can work as an agonist at the glycine sites of N-methyl-d-aspartate receptor (NMDAR). Interestingly, both types of glutamatergic modulators, NMDAR enhancers and blockers, can improve depression through common targets, namely alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionaic acid receptors (AMPARs) and mammalian target of rapamycin (mTOR). To elucidate the cellular signaling pathway underlying this counterintuitive observation, we activated NMDARs in rats by using d-serine. Saline, ketamine (NMDAR antagonist), and desipramine (tricyclic antidepressant) were used as controls. The antidepressant-like effects of all agents were evaluated using the forced swim test. The activation of the AMPAR-mTOR signaling pathway, release of brain-derived neurotrophic factor (BDNF), and alteration of AMPAR and NMDAR trafficking in the hippocampus of rats were examined. A single high dose of d-serine exerted an antidepressant-like effect that was mediated by rapid AMPAR-induced mTOR signaling pathway and increased BDNF proteins, identical to that of ketamine. Furthermore, in addition to the increased protein kinase A phosphorylation of the AMPAR subunit GluR1 (an indicator of AMPAR insertion in neurons), treatment with individual optimal doses of d-serine and ketamine also increased adaptin β2-NMDAR association (an indicator of the intracellular endocytic machinery and subsequent internalization of NMDARs). Desipramine did not influence these processes. Our study is the first to demonstrate an association between d-serine and ketamine; following adaptative regulation of AMPAR and NMDAR may lead to common changes of them. These findings provide novel targets for safer antidepressant agents with mechanisms similar to those of ketamine.

No abstract

When the prevalence of UTI after urodynamic examination is higher than 10%, we recommend that prophylactic antibiotics should be given for high-risk patients with parameters such as older age, diabetes and multipara (>3). Those who have UTI before urodynamic examination and who are found to have a low average flow rate of less than 7 mL/second should take prophylactic antibiotics after examination.

Asthma is the result of chronic inflammation of the airways which subsequently results in airway hyper-responsiveness and airflow obstruction. It has been shown that an elicited expression of acidic mammalian chitinase (AMCase) may be involved in the pathogenesis of asthma. Our recent study has demonstrated that the specific suppression of elevated AMCase leads to reduced eosinophilia and Th2-mediated immune responses in an ovalbumin (OVA)-sensitized mouse model of allergic asthma. In the current study, we show that the elicited expression of AMCase in the lung tissues of both ovalbumin- and Der P2-induced allergic asthma mouse models. The effects of allergic mediated molecules on AMCase expression were evaluated by utilizing promoter assay in the lung cells. In fact, the exposure of chitin, a polymerized sugar and the fundamental component of the major allergen mite and several of the inflammatory mediators, showed significant enhancement on AMCase expression. Such obtained results contribute to the basis of developing a promising therapeutic strategy for asthma by silencing AMCase expression.