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Autophagy has a dual role in the maintenance of cancer stem cells (CSCs), but the precise relationship between autophagy and cancer stemness requires further investigation. In this study, it was found that luminal and triple-negative breast cancers require distinct therapeutic approaches because of their different amounts of autophagy flux. We identified that autophagy flux was inhibited in triple-negative breast cancer (TNBC) CSCs. Moreover, miRNA-181a (miR-181a) expression is upregulated in both TNBC CSCs and patient tissues. Autophagy-related 5 (ATG5) and autophagy-related 2B (ATG2B) participate in the early formation of autophagosomes and were revealed as targets of miR-181a. Inhibition of miR-181a expression led to attenuation of TNBC stemness and an increase in autophagy flux. Furthermore, treatment with curcumin led to attenuation of cancer stemness in TNBC CSCs; the expression of ATG5 and ATG2B was enhanced and there was an increase of autophagy flux. These results indicated that ATG5 and ATG2B are involved in the suppression of cancer stemness in TNBC. In summary, autophagy inhibits cancer stem- ness through the miR-181a-regulated mechanism in TNBC. Promoting tumor-suppressive autophagy using curcumin may be a potential method for the treatment of TNBC. [ABSTRACT FROM AUTHOR]

Autosomal polycystic kidney disease (ADPKD) is a highly prevalent genetic renal disorder in which epithelial-lining fluid-filled cysts appear in kidneys. It is accompanied by hyperactivation of cell proliferation, interstitial inflammation, and fibrosis around the cyst lining cells, finally reaching end-stage renal disease. Previously, we found high expression of ligands stimulating the receptor for advanced glycation end products (RAGE) in ADPKD mice. Furthermore, gene silencing of RAGE was revealed to cause reduction of cystogenesis via down-regulation of cell proliferation in vitro, and intravenous administration of anti-RAGE adenovirus in vivo also displayed alleviation of the disease. Here, we attempted to identify the role of soluble RAGE (sRAGE) in inhibiting the progression of ADPKD using 2 different ADPKD mouse models. sRAGE is an endogenously expressed form of RAGE that has no membrane-anchoring domain, thereby giving it the ability to neutralize the ligands that stimulate RAGE signals. Both overexpression of sRAGE and sRAGE treatment blocked RAGE-mediated cell proliferation in vitro. In addition, sRAGE-injected ADPKD mice showed reduced cysts accompanied by enhanced renal function, inhibition of cell proliferation, inflammation, and fibrosis. These positive therapeutic effects of sRAGE displayed little liver toxicity, suggesting it as a new potential therapeutic target of ADPKD with low side effects. [ABSTRACT FROM AUTHOR]

Methamphetamine (MAP) is a commonly used, addictive drug, and a powerful stimulant that dramatically affects the central nervous system. In this study, we used the conditioned place preference (CPP) paradigm in order to study the reinforcing properties of MAP and the herewith associated changes in proteins within the mesolimbic dopamine system. A CPP was induced by MAP after three intermittent intraperitoneal injections (1 mg/kg) in rats and protein profiles in the nucleus accumbens, striatum, prefrontal cortex, cingulate cortex and hippocampus were compared with a saline-treated control group. In addition, a group of animals was run through extinction and protein profiles were compared with a non-extinguished group. Protein screening was conducted using two-dimensional electrophoresis analysis which identified 27 proteins in the group that showed MAP-induced CPP. Some of the proteins were confirmed by Western lot analysis. Identified proteins had functions related to the cytoskeleton, transport/endocytosis or exocytosis (e.g. profilin-2 and syntaxin-binding protein), and signal transduction, among others. [ABSTRACT FROM AUTHOR]

A thermostable DNA poiymerase from Thermus catdophilus GK24 was purified to near homogeneity by chromatographic methods, including ion-exchange, get-filtration and affinity chromatography. The purified enzyme had a specific activity of 8400 U/mg at 75°C and a molecular mass of 95 kDa, estimated by SDS/PAGE and Superose-12 gel filtration. Reaction conditions were investigated in terms of pH, metal-ion concentration and temperature. Experimental results showed that T. caldophilus (Tca) DNA polymerase had a maximum activity new pH 8.7 at 75 °C. The N-terminal sequence of the enzyme was highly similar to that of Thermus aquaticus (Taq) DNA polymerase, which was consistent with the Fact that the enzyme had 5'-to3' exonuclease activity and no 3'-to-5' exonuclease activity. Gene amplification using Tca DNA polymerase resulted in longer products than amplification using Taq DNA polymerase. [ABSTRACT FROM AUTHOR]