The roles of adenosine signaling in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multiple etiological factors. Immune disorder contributes to SLE development and is an important clinical manifestation of SLE patients. Immune dysfunction is characterized by abnormal of B cells, T cells, monocyte-macrophages and dendritic cells (DCs), in both quantity and quality. Adenosine is a critical factor for human immune homeostasis, which acts as an immunosuppressive signal and can prevent the hyperactivity of human immune system. Adenosine levels are significant decreased in serum from SLE patients. Adenosine level is regulated by the CD39, CD73 and adenosine deaminase (ADA). CD39/CD73/ADA catalyzed the cascade enzymatic reaction, which contained the adenosine generation and degradation. Adenosine affects the function of various immune cells via bind to the adenosine receptors, which are expressed on the cell surface. This review aims to export the changes of immune cells and adenosine signal pathway in SLE, as well as the effect of adenosine signal pathway in SLE development.

Down-regulation of DPP4 by TGFß1/miR29a-3p inhibited proliferation and promoted migration of ovarian cancer cells.

OBJECTIVE: To explore the DPP4 expression changes and functions in ovarian cancer (OV), as well as the regulation mechanism for DDP4. METHODS: GEPIA2, GSE18520, GSE26712 and UALCAN were used to analyze differences in DPP4 expression between OV tumors and control tissues. Serum DPP4 levels were measured by ELISA. The prognostic values of DPP4 were evaluated using a Kaplan-Meier (KM) plotter. Small interfering RNA was used for DPP4 knockdown in OVCAR-3 and SKOV-3 cells. CCK-8 and scratch healing assays were used to determine the cells' proliferation and migration abilities. Flow cytometry (FCM) was used to detect the cell cycle and apoptosis. A dual-luciferase assay was designed to confirm the regulatory effect of miR-29a-3p on DPP4. RESULTS: The expressions of DPP4 mRNA and protein were decreased in OV tumor tissues. Serum DPP4 levels decreased in OV patients. KM plotter analysis showed correlation between high DPP4 expression and a poor prognosis in OV patients. By targeting knockdown of DPP4, we found that OVCAR-3 and SKOV-3 cells' proliferation was inhibited, while cell's migration ability was significantly promoted. FCM analysis showed that DPP4 knockdown induced a decrease in the S phase. Furthermore, DPP4 was shown to be downregulated by miR-29a-3p and TGFß1 in OVCAR-3 cells, and miR-29a-3p expression was upregulated by TGFß1. The effects of miR-29a-3p and TGFß1 on OVCAR-3 cells' biological behaviors were consistent with DPP4 knockdown. CONCLUSION: DPP4 was downregulated in OV patients. DPP4 knockdown significantly inhibited OVCAR-3 and SKOV-3 cell proliferation and promoted cell migration. DDP4 can be downregulated by TGFß1 through the upregulation of miR-29a-3p in OV cells.

Synthesis, characterization, cell imaging and anti-tumor activity of multifunctional nanoparticles.

Most anticancer complexes are unable to differentiate between diseased and healthy cells, systemic toxicity and undesired side effects can result. In the current study, a PEG and RGD peptides functionalized fluorescent dye Rhodamine B isothiocyanate (RBITC) doped magnetic silica nanoparticle (MnFe(3)O(4)@SiO(2)-PEG-RGD), carrying a anticancer superparamagnetic Mn(II) complex, was synthesized and characterized using spectroscopic methods. The multifunctional nanoparticles (MnFe(3)O(4)@SiO(2)-PEG-RGD) can image HepG-2 cells and differentiate between HepG-2 and WRL-68 cells based on T(1) MR imaging technology. The in vitro fluorescence image and inhibition assay on the proliferation of HeLa cells indicate that MnFe(3)O(4)@SiO(2)-PEG-RGD nanoparticles can effectively reach the tumor site, be internalized by endocytosis and then retain in cancer cells due to the retention effect of nanoparticles. This study demonstrated that a PEG and RGD peptides functionalized silica nanoparticle was a good carrier for the anticancer complexes, and the anticancer complexes loaded multifunctional nanoparticles could be developed as special agents in monitoring therapy of cancer.

Synthesis of novel derivatives of bispodophyllotoxin as potential antineoplastic agents--part XVI.

Podophyllotoxin and related analogs present numerous challenges associated with optimal antitumor activity and severe unpredictable toxicity. In an attempt to find biorational podophyllotoxin-related drug, two moieties of podophyllotoxin have been linked at C4-position by a simple modification of the carbodiimide procedure to provide novel bispodophyllotoxin analogs (4a-4e) and their structural information was extensively characterized by using 1H-NMR, IR, and HRMS.