Metabolic response by F-FDG was effective in predicting efficacy and survival at 1 month after nivolumab treatment.

Interleukin (IL)-10 is a contributing factor to neuroprotection of mesenchymal stem cell (MSC) transplantation after ischemic stroke. Our aim was to increase therapeutic effects by combining MSCs and ex vivo IL-10 gene transfer with an adeno-associated virus (AAV) vector using a rat transient middle cerebral artery occlusion (MCAO) model. Sprague-Dawley rats underwent 90 min MCAO followed by intravenous administration of MSCs alone or IL-10 gene-transferred MSCs (MSC/IL-10) at 0 or 3 hr after ischemia reperfusion. Infarct lesions, neurological deficits, and immunological analyses were performed within 7 days after MCAO. 0-hr transplantation of MSCs alone and MSC/IL-10 significantly reduced infarct volumes and improved motor function. Conversely, 3-hr transplantation of MSC/IL-10, but not MSCs alone, significantly reduced infarct volumes (p < 0.01) and improved motor function (p < 0.01) compared with vehicle groups at 72 hr and 7 days after MCAO. Immunological analysis showed that MSC/IL-10 transplantation significantly inhibits microglial activation and pro-inflammatory cytokine expression compared with MSCs alone. Moreover, overexpressing IL-10 suppressed neuronal degeneration and improved survival of engrafted MSCs in the ischemic hemisphere. These results suggest that overexpressing IL-10 enhances the neuroprotective effects of MSC transplantation by anti-inflammatory modulation and thereby supports neuronal survival during the acute ischemic phase.

No abstract

Effects ofaxenoblotlc estrogen, blsphenol A (SPA), on reproductive functions were Investigated using adult male rats. SPA was dissolved Into sesame 011 and Injected sc every day (1 mglrat) for 14 days. Animals were killed by decapitation after the final administration of SPA, and the trunk blood, pituItary , and testes were collected.. Plasma concentrations of prolactin were dramatically Increased and pituitary contents of prolactin were slightly Increased In the SPA group compared to the control group. Plasma concentrations of testosterone were decreased and plasma concentrations of LH were increased In SPA-treatedrats compared to control rats. Testicular contents of Inhlbln were decreased In SPA-treated rats compared to control rats, although plasma concentrations of Inhlbln were not changed after administration of SPA. The testicular response to hCG for progesterone and testosterone release was decreased In SPA-treated rats. Administration of SPA did not change the pituitary response to luteinizing hormonereleasing hormone (LH-RH) In castrated male rats treated with testosterone. Male sexual behavior also was not changed as a result of SPA treatment. These results suggest that SPA directly Inhibits testicular functions and the Increased level of plasma LH Is probably due to a reduction In the negative feedback regulation by testosterone. The testis Is probably a more sensitive site for SPA action than the hypothalamus-pituitary axis.

Extensive fusion was induced in mouse alveolar macrophages by treatment with conditioned media obtained from spleen cell cultures treated with 15 ,ug of phytohemagglutinin or concanavalin A per ml or with 12 nM la,25-dihydroxyvitamin D3 [la,25(OH)2D31. The fusion rate was 80-90% on day 3. In addition, 1a,25(OH)2D3 added directly to alveolar macrophages induced fusion of about 35% of the cells on day 3, whereas direct addition of phytohemagglutinin and concanavalin A did not enhance fusion at all. When conditioned media from spleen cell or T cell cultures treated with 12 nM Ia,25(OH)2D3 were applied to a Sephadex G-100 column, a fusion factor (Mr 37,000-70,000) could be separated from Ia,25(OH)2D3. la,25(OH)2D3 induced fusion at 0.012-120 nM in a dose-dependent manner both by direct action and by spleen cell-mediated indirect action, but the fusion rate was always much greater in the latter than in the former at each concentration of the vitamin. Of the vitamin D3 derivatives tested, Ia,25(OH)2D3 was the most potent, followed successively by la,24R,25-trihydroxyvitamin D3, la-hydroxyvitamin D3, 25-hydroxyvitamin D3, and 24R,25-dihydroxyvitamin D3. These results clearly indicate that 1a,25(OH)2D3 induces fusion of mouse alveolar macrophages by both a direct and an indirect mechanism, the latter mediated by spleen cells, probably by T cells.Vitamin D3 is well known as an antirachitic agent that stimulates bone mineralization. In 1952, Carlsson demonstrated for the first time that vitamin D stimulates not only bone mineralization but also bone mineral mobilization (1). Vitamin D3 is metabolized first in the liver to 25-hydroxyvitamin D3 [25-(OH)D3] and then in the kidney mainly to 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] and la,25-dihydroxyvitamin D3