Prostaglandin I2 Signaling Drives Th17 Differentiation and Exacerbates Experimental Autoimmune Encephalomyelitis

BACKGROUND: Prostaglandin I(2) (PGI(2)), a lipid mediator currently used in treatment of human disease, is a critical regulator of adaptive immune responses. Although PGI(2) signaling suppressed Th1 and Th2 immune responses, the role of PGI(2) in Th17 differentiation is not known. METHODOLOGY/PRINCIPAL FINDINGS: In mouse CD4(+)CD62L(+) naïve T cell culture, the PGI(2) analogs iloprost and cicaprost increased IL-17A and IL-22 protein production and Th17 differentiation in vitro. This effect was augmented by IL-23 and was dependent on PGI(2) receptor IP signaling. In mouse bone marrow-derived CD11c(+) dendritic cells (BMDCs), PGI(2) analogs increased the ratio of IL-23/IL-12, which is correlated with increased ability of BMDCs to stimulate naïve T cells for IL-17A production. Moreover, IP knockout mice had delayed onset of a Th17-associated neurological disease, experimental autoimmune encephalomyelitis (EAE), and reduced infiltration of IL-17A-expressing mononuclear cells in the spinal cords compared to wild type mice. These results suggest that PGI(2) promotes in vivo Th17 responses. CONCLUSION: The preferential stimulation of Th17 differentiation by IP signaling may have important clinical implications as PGI(2) and its analogs are commonly used to treat human pulmonary hypertension

Bis(4-aminopyridinium) tetraiodidocadmate monohydrate

The title compound, (C5H7N2)2[CdI4]·H2O, contains one [CdI4]2− anion, two prontonated 4-aminopyridine molecules and one water molecule in the asymmetric unit. In the anion, the CdII atom is coordinated by four I atoms in a slightly distorted tetrahedral geometry. The [CdI4]2− anion and the water molecule are bisected by a crystallographic mirror plane perpendicular to the c-axis direction, with the CdII atom, two of the I atoms and the atoms of the water molecule located on this plane. The crystal packing is stabilized by intermolecular N—H...I, N—H...O and O—H...I hydrogen bonds and by π–π stacking interactions [centroid–centroid distance = 3.798 (3) Å) between pyridine rings, which build up a three-dimensional network

Combination of Vitamin C and Lenvatinib potentiates antitumor effects in hepatocellular carcinoma cells in vitro

Lenvatinib has become a first-line drug in the treatment of advanced hepatocellular carcinoma (HCC). Investigating its use in combination with other agents is of great significance to improve the sensitivity and durable response of Lenvatinib in advanced HCC patients. Vitamin C (L-ascorbic acid, ascorbate, VC) is an important natural antioxidant, which has been reported to show suppressive effects in cancer treatment. Here, we investigated the effect of the combination of VC and Lenvatinib in HCC cells in vitro. We found that treatment of VC alone significantly inhibited the proliferation, migration and invasion in HCC cells. Additionally, VC was strongly synergistic with Lenvatinib in inhibition of the proliferative, migratory and invasive capacities of HCC cells in vitro. In conclusion, our results demonstrate that the combination of VC and Lenvatinib has synergistic antitumor activities against HCC cells, providing a promising therapeutic strategy to improve the prognosis of HCC patients

Effects of Precipitant and pH on Coprecipitation of Nanosized Co-Cr-V Alloy Powders

Nanosized Co-Cr-V alloy powders were synthesized via coprecipitation method. Effects of precipitants ((NH4)2C2O4·H2O and Na2CO3) and pH were investigated by X-ray diffraction (XRD), Zeta potential analyzer, thermogravimetry-differential scanning calorimetry (TG-DSC), inductively coupled plasma-atomic emission spectrometry (ICP-AES) and scanning electron microscopy (SEM). Co-Cr-V alloy powders were consisted of major face-centered cubic Co (fcc Co) and minor hexagonal close-packed Co (hcp Co). Grain sizes of precursors and Co-Cr-V alloy powders were increased with pH value (7–10) within the ranges of 3~39 and 39~66 nm, respectively. Rod-like or granular Co-Cr-V alloy particles were assembled by interconnected nanograins. At pH = 7, Na2CO3 precipitant was found to be beneficial to maintain the desirable composition of Co-Cr-V powders. It was also found that lower pH favors the maintenance of pre-designed composition, while grain coarsens at higher pH. Effects of variation for precipitant and pH on the morphology and composition of Co-Cr-V alloy powder were discussed in detail and relevant mechanism was further proposed