Abnormal tryptophan metabolism is linked to cancer and neurodegenerative diseases, and tryptophan metabolites have been reported as potential prostate cancer (PCa) biomarkers. However, little is known about the bioactivities of tryptophan metabolites on PCa cell growth. In this study, MTT and transwell assays were used to study the cytotoxicities of 13 major tryptophan metabolites on PCa and normal prostate epithelial cell lines. Ultraperformance liquid chromatography–high resolution mass spectrometry (UPLC–HRMS) was used to analyze metabolic changes in cells treated with tryptamine. Flow cytometry, confocal imaging, and Western blot were used to test the apoptosis induced by tryptamine. It was shown that tryptamine had obvious inhibitory effects on PCa cell lines PC-3 and LNCaP, stronger than those on the normal prostate cell line RWPE-1. Tryptamine was further shown to induce apoptosis and inhibit PC-3 cell migration. Metabolic changes including amino acid metabolism related to cell proliferation and metastasis were found in PC-3 cells treated with tryptamine. Furthermore, a PC-3 xenograft mouse model was used to study the effect of tryptamine in vivo. The intratumoral injection of tryptamine was demonstrated to significantly reduce the tumor growth and tumor sizes in vivo; however, intraperitoneal treatment resulted in increased tumor growth. Such dual effects in vivo advanced our understanding of the bioactivity of tryptamine in regulating prostate tumor development, in addition to its major role as a neuromodulator.

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The aim of the present research is to prepare well dense sintered nano-SiC. Two samples of Nano-silicon carbide prepared by pyrolysis of rice-husk ashes as starting materials. The first was fine (hand-ground) rice-husk ash, and the second was prepared by ball milled technology. The firing temperature to obtain well crystalline nano SiC was 1550 o C. The effect of pyrolysis under vacuum atmosphere had been tested. Herein the liquid phase sintering is used as a good sintering technique. The oxides sintering additives (3 wt% Y2O3 and 7wt% Al2O3) play very crucial role in decreasing the apparent porosity and increasing the relative density of the sintered body if compared with that prepared without any oxide additives. Different sintering temperature firing range was applied here, and the optimum firing temperature that used to obtain well dense sintered SiC was 1950 o C. With decreasing additive content, the consolidation of the materials became increasingly dependent on solid-state sintering. The microstructure underwent a transition from a microcrystalline matrix with nano-crystalline second phase (micro-nano) to a nano-crystalline matrix with nano-crystalline second phase (nano-nano) when the yttria and alumina content was lowered to 3 wt%.

The discovery of new anticancer drugs targeting the PD-1/PD-L1 pathway has been research hotspots. In this study, a combination of biological affinity ultrafiltration (BAU), UPLC-HRMS, molecular dynamic (MD) simulations and molecular docking methods were applied to search for endogenous active compounds that can inhibit the binding of PD-L1 and PD-1. We screened dozens of potential cancer related endogenous compounds. The results showed that cyclic adenosine monophosphate (cAMP) had a direct inhibition effect on the PD-1/PD-L1 binding with an in vitro IC50 value of about 2.7 uM determined by homogeneous time-resolved fluorescence (HTRF) assay. The binding mode analyses for the cAMP - dimeric/monomeric PD-L1 complex indicated that cAMP was likely to bind to the dimeric PD-L1, since the binding free energies of the cAMP - dimeric and monomeric PD-L1 complex were about 23.6 and 15.1 kcal/mol, respectively, from MD simulations. The direct binding assay using surface plasmon resonance (SPR) method showed that cAMP could also bind to monomeric PD-L1 fixed on the sensor chip surface with a KD value of about 1.72 mM. Our findings suggested that cAMP may directly inhibit the PD-1/PD-L1 interaction.