Macrophages are versatile phagocytic cells in immune system with immunoregulatory functions. However, the removal of apoptotic cells by macrophages is disturbed in systemic lupus erythematosus (SLE). Aryl hydrocarbon receptor (AhR) is a ligand-activated cytoplasmic receptor and transcription factor with diverse effects on immune response. Indole-3-carbinol (I3C) is an AhR agonist which has been implicated as a beneficial factor in regulating inflammation and cytokine expression in murine models of SLE. However, the molecular mechanisms are not thoroughly studied. Here, we aimed to investigate the ex vivo effects of I3C on polarization of monocyte-derived macrophages (MDMs) in SLE patients and the expression of regulatory cytokines upon AhR activation. MDMs from 15 newly diagnosed SLE patients and 10 normal subjects were induced by Jurkat apoptotic bodies (JABs) and treated with I3C. I3C enhanced the nuclear accumulation of AhR among MDMs of SLE patients and altered the expression of AhR target genes including CYP1A1, IL1- β, IDO-1 and MRC-1. The imbalanced expression of pro- and anti- inflammatory cytokines (IL-10, IL-12, TGFβ1, TNFα, IL-23, IL-6 and IFN-γ) was compensated in response to I3C. AhR activation was also associated with the overexpression of M2 markers (CD163) and downregulation of M1 markers (CD86). Thus, macrophages are activated alternatively in response to I3C. The obtained data indicate that I3C-mediated AhR activation possess immunoregulatory effects on macrophages of SLE patients by exerting an obvious downregulation in the expression of pro-inflammatory and overexpression of anti-inflammatory cytokines. Therefore, AhR could be targeted and further investigated as a choice of anti-inflammatory therapies for autoimmune disorders such as SLE.

Curcumin is a potent natural anticancer agent, but its effectiveness is limited by properties such as very low solubility, high rate of degradation, and low rate of absorption of its hydrophobic molecules in vivo. To date, various nanocarriers have been used to improve the bioavailability of this hydrophobic biomaterial. This study investigates the encapsulation of curcumin in a novel nanostructure of monomethoxy poly(ethylene glycol)-oleate (mPEG-OA) and its anticancer effect. Tests were done to determine the critical micelle concentration (CMC), encapsulation efficiency, drug-loading efficiency, and cytotoxicity (against U87MG brain carcinoma cells and HFSF-PI3 cells as normal human fibroblasts) of some nanodevice preparations. The results of fluorescence microscopy and cell-cycle analyses indicated that the in vitro bioavailability of the encapsulated curcumin was significantly greater than that of free curcumin. Cytotoxicity evaluations showed that half maximal inhibitory concentrations of free curcumin and curcumin-loaded mPEG-OA for the U87MG cancer cell line were 48 µM and 24 µM, respectively. The Annexin-V-FLUOS assay was used to quantify the apoptotic effect of the prepared nanostructures. Apoptosis induction was observed in a dose-dependent manner after curcumin-loaded mPEG-OA treatments. Two common self-assembling structures, micelles and polymersomes, were observed by atomic force microscopy and dynamic light scattering, and the abundance of each structure was dependent on the concentration of the diblock copolymer. The mPEG-OA micelles had a very low CMC (13.24 µM or 0.03 g/L). Moreover, atomic force microscopy and dynamic light scattering showed that the curcumin-loaded mPEG-OA polymersomes had very stable structures, and at concentrations 1,000 times less than the CMC, at which the micelles disappear, polymersomes were the dominant structures in the dispersion with a reduced size distribution below 150 nm. Overall, the results from these tests revealed that this nanocarrier can be considered as an appropriate drug delivery system for delivering curcumin to cancer cells.

Background: Colorectal cancer is one of the most commonly diagnosed cancers and cancer- related death worldwide. Identification of new specific biomarkers could be helpful to detection of this malignancy. Altered plasma microRNA expression has been identified in many cancers, including colorectal cancer. Objectives: The main objective of this study was to identify the circulating microRNAs with the most expression changes in colorectal cancer patients compared with neoplasm free healthy individuals. Materials and Methods: MicroRNA expression profiling was performed on plasma samples of 37 colorectal cancer patients and 8 normal subjects using microRNA microarray. Quantitative real-time reverse transcription polymerase chain reaction was used to validate the two selected altered microR NAs. Plasma samples from 61 colorectal cancer patients and 24 normal subjects were used in our validation study. Results: In profiling study we found a panel of six plasma microRNAs with significant downregulation. MicroRNA-142-3p and microRNA-26a-5p were selected and validated by polymerase chain reaction. Our results demonstrated that expression levels of plasma microRNA-142-3p and microRNA-26a-5p were significantly downregulated in patients with colorectal cancer when compared to control group. Conclusions: Our findings suggest that downregulation of plasma microRNA-142-3p and microRNA-26a-5p might serve as novel noninvasive biomarkers in the diagnosis of colorectal cancer, although more studies are needed to highlight the theoretical strengths. Keywords: Biomarkers; Circulating%20microRNA">>Circulating microRNA; Microarray; Early Detection