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Breast cancer is a common malignant tumor with a high incidence of recurrence and metastasis. It has been reported that propofol has certain anti-breast cancer effects, but the intrinsic molecular mechanism remains unclear. This study investigated the effect of propofol on breast cancer MCF-7 cells and its possible regulatory mechanisms. MCF-7 cells were treated by propofol, and then the effects of propofol on cell growth and epithelial-mesenchymal transition (EMT) were studied. We subsequently testified whether miR-21 was a downstream effector of propofol. As a result, propofol repressed the proliferation and migration of MCF-7 cells, but significantly induced apoptosis. Meanwhile, miR-21 expression and EMT were inhibited by propofol stimulation. The effects of propofol on MCF-7 cells proliferation, apoptosis and EMT were all attenuated when miR-21 was overexpressed. Besides this, the activation of PI3K/AKT and Wnt3a/β-catenin pathways was reduced by propofol stimulation in a miR-21-depedent manner. In conclusion, propofol can inhibit the proliferation and EMT of MCF-7 cells by down-regulating miR-21 expression. Moreover, miR-21 can further regulate PI3K/AKT and Wnt/β-catenin pathways. [ABSTRACT FROM AUTHOR]

Porcine circovirus 3 (PCV3) was found to be associated with reproductive disease in pigs, and since its first identification in the United States, it subsequently spread worldwide, especially in China, where it might pose a potential threat to the porcine industry. However, no exhaustive analysis was performed to understand its evolution in the prospect of codon usage pattern. Here, we performed a deep codon usage analysis of PCV3. PCV3 sequences were classified into two clades: PCV3a and PCV3b, confirmed by principal component analysis. Additionally, the degree of codon usage bias of PCV3 was slightly low as inferred from the analysis of the effective number of codons. The codon usage pattern was mainly affected by natural selection, but there was a co-effect of mutation pressure and dinucleotide frequency. Moreover, based on similarity index analysis, codon adaptation index analysis and relative codon deoptimization index analysis, we found that PCV3 might pose a potential risk to public health though with unknow pathogenicity. In conclusion, this work reinforces the systematic understanding of the evolution of PCV3, which was reflected by the codon usage patterns and fitness of this novel emergent virus. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have shown that mitochondrial division inhibitor 1 (mdivi-1) protects rat brain from ischemia/reperfusion (I/R) injury, but the precise mechanisms are unclear. This study aims to elucidate the effect of mdivi-1 on energy metabolism and neuronal apoptosis induced by I/R in vitro. Methods: Cultured hippocampal neurons from Wistar rats were randomly divided into four treatment groups: control (C), vehicle (V), I/R (I), and I/R plus mdivi-1 (M). Ischemia/reperfusion was induced by oxygen-glucose deprivation for 6 h followed by normoxic/normoglycemic reperfusion for 20 h. Neurons in the M group were pretreated with mdivi-1 for 40 min before I/R. Expression levels of the mdiv-1 target dynamin-related protein 1 and apoptosis regulators Bcl-2 and Bax were examined by Western blotting. Mitochondrial membrane potential () was measured by flow cytometry. Intracellular ATP content and the activities of mitochondrial complexes I−IV, Na+-K+-ATPase, and Ca2+-Mg2+-ATPase were measured by standard assays. Results: Compared to group I neurons, group M neurons exhibited markedly reduced Drp-1 and Bax expression, higher Bcl-2 expression, , and intracellular ATP, and elevated mitochondrial complex I−IV, Na+-K+-ATPase, and Ca2+-Mg2+-ATPase activities. Conclusion: Inhibition of mitochondrial fission significantly improved mitochondrial function and suppressed apoptotic signaling induced by I/R. [ABSTRACT FROM AUTHOR]

Context: Transdermal local anesthesia is one of the most applied strategies to avoid systemic adverse effects; there is an appealing need for a prolonged local anesthetic that would provide better bioavailability and longer pain relief with a single administration. Objective: Layer-by-layer (LBL) technique was used in this study to explore a nanosized drug delivery system for local anesthetic therapy. Materials and methods: LBL-coated lidocaine-loaded nanostructured lipid nanoparticles (LBL-LA/NLCs) were prepared and characterized in terms of particle size (PS), zeta potential, drug encapsulation efficiency (EE),in vitroskin permeation andin vivolocal anesthetic studies. Results: Evaluation of thein vitroskin permeation andin vivoanesthesia effect illustrated that LBL-LA/NLCs can enhance and prolong the anesthetic effect of LA. Discussion and conclusion: LBL-LA/NLCs could function as a promising drug delivery strategy for overcoming the barrier function of the skin and could deliver anesthetic through the skin with sustained release behavior for local anesthetic therapy. [ABSTRACT FROM AUTHOR]

Purpose: The skin permeation enhancement of local anesthetics by newer innovative nanotechnologies has been an appealing field recently. However, which nanocarrier is better for drug loading and has better stability? Therefore, the aim of our study was to compare two kinds of nanocarriers: liposomes and lipid–polymer hybrid nanoparticles (LPNs) for lidocaine (LA) delivery. Methods: LA-loaded liposomes (LA-LPs) and LPNs (LA-LPNs) were prepared. Two kinds of nanocarriers were characterized in terms of particle size, zeta potential, drug encapsulation efficiency (EE), drug release, and stability. Theirin vitroskin permeation was studied using a Franz diffusion cell mounted with depilated mouse skinin vitro. In vivolocal anesthetic effects of LA containing formulations were evaluated by tail flick latency (TFL) test using a tail-flick measuring device. Results: Compared with LA-LPs, LA-LPNs showed significantly betterin vitroskin permeation ability andin vivolocal anesthetic effects. Conclusion: The results demonstrated that LPNs could improve the efficacy of drugs to higher levels than LPs and free drugs, thus could serve as an effective drug system for LA loading for local anesthetic therapy. [ABSTRACT FROM PUBLISHER]

It is known that mitochondrial ATP-sensitive potassium channels (mitoKATP) play a significant role in protecting cerebral function from ischemia-reperfusion injury, which is related with a decrease in the mitochondrial matrix calcium. However, the effect of mitochondrial calcium uniporter (MCU) on diazoxide-induced cerebral protection is still indistinct. The purpose of the present paper is to further observe the relationship between mitoKATP and MCU, and to probe the mechanism. Adult male Wistar rats were randomly divided into five groups: the Sham group, the I-R group, the Dzx+I-R group, the Dzx+Sper+I-R group, and the Sper+I-R group. Rats not in the Sham group were exposed to 2-hour ischemia followed by 24-hour reperfusion. Diazoxide and spermine were administrated 30 minutes before ischemia or 10 minutes before reperfusion, respectively. After 24-hour reperfusion, animals were given neurological performance tests, overdosed with general anesthesia, and then their brains were excised for infarct volume, pathological changes, and apoptosis analysis. The beneficial effects of diazoxide (improved neurological deficits, decreased infarct volume, and apoptosis, evidenced by the decreased expression of cytochrome c and Bax) were significantly neutralized by spermine. The results of the present work suggest that diazoxide-induced cerebral protection against ischemia-reperfusion injury is mediated by spermine through apoptotic pathway. [ABSTRACT FROM AUTHOR]