TRPV1 activation impedes foam cell formation by inducing autophagy in oxLDL-treated vascular smooth muscle cells

Vascular smooth muscle cells (VSMCs) are an important origin of foam cells besides macrophages. The mechanisms underlying VSMC foam cell formation are relatively little known. Activation of transient receptor potential vanilloid subfamily 1 (TRPV1) and autophagy have a potential role in regulating foam cell formation. Our study demonstrated that autophagy protected against foam cell formation in oxidized low-density lipoprotein (oxLDL)-treated VSMCs; activation of TRPV1 by capsaicin rescued the autophagy impaired by oxLDL and activated autophagy–lysosome pathway in VSMCs; activation of TRPV1 by capsaicin impeded foam cell formation of VSMCs through autophagy induction; activation of TRPV1 by capsaicin induced autophagy through AMP-activated protein kinase (AMPK) signaling pathway. This study provides evidence that autophagy plays an important role in VSMC foam cell formation and highlights TRPV1 as a promising therapeutic target in atherosclerosis.     

Mixed Polyethylene Glycol-Modified Breviscapine-Loaded Solid Lipid Nanoparticles for Improved Brain Bioavailability: Preparation,Characterization, and In Vivo Cerebral Microdialysis Evaluation in Adult Sprague Dawley Rats

Breviscapine is used in the treatment of ischemic cerebrovascular diseases, but it has a low bioavailability in the brain due to its poor physicochemical properties and the activity of P-glycoprotein efflux pumps located at the blood–brain barrier. In the present study, breviscapine-loaded solid lipid nanoparticles (SLN) coated with polyethylene glycol (PEG) derivatives were formulated and evaluated for their ability to enhance brain bioavailability. The SLNs were either coated with polyethylene glycol (40) (PEG-40) stearate alone (Bre-GBSLN-PS) or a mixture of PEG-40 stearate and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG2000 (DSPE-PEG₂₀₀₀) (Bre-GBSLN-PS-DSPE) and were characterized both in vitro and in vivo. The mean particle size, polydispersity index, and entrapment efficiency for Bre-GBSLN-PS and Bre-GBSLN-PS-DSPE were 21.60 ± 0.10 and 22.60 ± 0.70 nm, 0.27 ± 0.01 and 0.26 ± 0.04, and 46.89 ± 0.73% and 47.62 ± 1.86%, respectively. The brain pharmacokinetic parameters revealed that the brain bioavailability of breviscapine from the Bre-GBSLN-PS and Bre-GBSLN-PS-DSPE was significantly enhanced (p < 0.01) with the area under concentration–time curve (AUC) of 1.59 ± 0.39 and 1.42 ± 0.58 μg h/mL of breviscapine, respectively, in comparison to 0.11 ± 0.02 μg h/mL from the commercial breviscapine injection. The ratios of the brain AUC for scutellarin in comparison with the plasma scutellarin AUC for commercial breviscapine injection, Bre-GBSLN-PS, and Bre-GBSLN-PS-DSPE were 0.66%, 2.82%, and 4.51%, respectively. These results showed that though both SLN formulations increased brain uptake of breviscapine, Bre-GBSLN-PS-DSPE which was coated with a binary combination of PEG-40 stearate and DSPE-PEG₂₀₀₀ had a better brain bioavailability than Bre-GBSLN-PS. Thus, the coating of SLNs with the appropriate PEG derivative combination could improve brain bioavailability of breviscapine and can be a promising tool for brain drug delivery.KEY WORDS: breviscapine, microdialysis, mixed PEGylation, P-glycoprotein (P-gp), solid lipid nanoparticles     

Magnesium Deficiency Enhances Hydrogen Peroxide Production and Oxidative Damage in Chick Embryo Hepatocyte In Vitro

Magnesium deficiency and oxidative stress have been identified as correlative factors in many diseases. The origin of free radicals correlated with oxidative damage resulting from Mg-deficiency is unclear at the cellular level. To investigate whether hydrogen peroxide (H₂O₂) is associated in the oxidative stress induced by Mg-deficiency, the effect of Mg²⁺ deficiency (0, 0.4, 0.7 mM) on the metabolism of H₂O₂ was investigated in cultured chick embryo hepatocytes. After being cultured in the media with various concentrations of Mg²⁺ for 1, 2, 4, 6 and 10 days, parameters of H₂O₂ production, catalase activity, lipid peroxidation, intracellular total Mg and cell viability were analyzed. Results demonstrated that long-term incubation of chick embryo hepatocyte in extracellular Mg²⁺-deprivative and Mg²⁺-deficient (0.4 mM) states significantly enhanced the production of H₂O₂ (approximately twofold, respectively) and lipid peroxidation in the cell cultures, while decreasing the cell viability. Additionally, the reversing action of Mg²⁺ re-added to 1.0 mM and the partial reversing action of dimethylthiourea suggested that (i) [Mg²⁺]_e deficiency induced the increase of H₂O₂ production, (ii) [Mg²⁺]_e deficiency decreased catalase activity in chick embryo hepatocyte in vitro, subsequently causing oxidative stress and cell peroxidative damage.     

陕南晚震旦世Gaojiashania的保存特征及形态解释

陕西宁强地区灯影组高家山段地层中特异原地埋藏的管状化石Gaojiashania Yang et al.,1986为体似蚕状或带状,直或微弯,由密集圆环（或皱脊）彼此连接在一起形成的管状化石,对化石的埋藏及保存特征的研究表明,不同的矿化阶段形成不同的保存特征,早期黄铁矿化对化石保存起着重要作用。Gaojiashania以其特殊的圆环叠置的保存方式,与软躯体蠕形动物化石以及遗迹化石的保存迥然不同,推测Gaojiashania生物体已具有分节现象,在成分上也有差别,圆环部分可能具有一定的矿化,属于较为高等的生物门类。     

Tobacco Knowledge among Adults in Zhejiang Province,China

Objective

The aims of current study were to assess the level of tobacco knowledge, anti-tobacco messages and major information channels in Zhejiang.

Methods

Face-to-face interviews were conducted with 2112 adults in Zhejiang. Data on demographic information, smoking status, tobacco knowledge, anti-tobacco messages and major information channels was collected.

Results

The findings revealed that only 31.87% of the population were aware that smoking could cause all three diseases (stoke, heart disease, and lung cancer), 86.09% were aware that smoking causes lung cancer, 46.43% and 42.40% were aware that smoking causes stroke and heart attack, respectively. Residence and education level had significant effects on awareness, while the effects of smoking status, gender, age, and household monthly income were not significant. There were five major information channels as follows: television (67.52%), newspapers or magazines (40.79%), billboards (30.02%), public walls (24.72), and radio (23.79%). Respondents got the following anti-tobacco messages from mass media: “No smoking in public” (66.34%), “No smoking in front of other people” (35.18%) and “Not offering cigarettes to one another” (22.82%).

Conclusions

The tobacco knowledge among residents in Zhejiang province is relatively poor. Improved information channels and content of anti-tobacco messages are necessary to increase the public’s tobacco knowledge, particularly among rural residents and people with less education.     

Effects of sand burial depth on the root system of Salix cheilophila seedlings in Mu Us Sandy Land, Inner Mongolia, China

Salix cheilophila Schneid. is a naturally occurring Salix species in Mu Us Sandy Land, Inner Mongolia, China. We focused on the morphological adaptability of S. cheilophila to sand dune burial. For morphological measurements, 32 S. cheilophila seedlings were removed from a community which was in the process of being buried by a shifting sand dune. Each seedling collected included the entire root system. We measured the number, length, and biomass of the adventitious roots, primary lateral roots, and taproot, and compared the morphological characteristics of the root system, including adventitious roots, for seedlings buried to various levels in the sand. The growth range of adventitious roots increased as the length of the buried portion of the main shoot increased. In addition, the total dry weight of all current-year shoots tended to increase gradually with increasing total dry weight of the adventitious roots. These results suggest that S. cheilophila tends to make use of the sedimentary sand layer that accompanies shifting sand dunes. However, there was no correlation between biomass or number of adventitious roots and the length of the buried part of the main shoot. Thus, S. cheilophila does not grow adventitious roots proportional to the buried part. These morphological characteristics of the root system, including the adventitious roots, may indicate that S. cheilophila has poor morphological adaptability to sand dune burial.     

Development of a novel feeding regime for large scale production of human umbilical cord mesenchymal stem/stromal cells

Cytotechnology - Human umbilical cord mesenchymal stem/stromal cells (hUC-MSCs) have attracted significant research interests in regenerative medicine and cell-based therapies due to their...     

Optimization of covalent immobilization of pectinase on sodium alginate support

Pectinase was immobilized on a sodium alginate support using glutaraldehyde and retained 66% activity. The optimal pH for activity shifted from 3.0 to 3.5 after immobilization; however, the optimum temperature remained unchanged at 40°C. The immobilized enzyme also had a higher thermal stability and reusability than the free enzyme, and retained 80% of initial activity after 11 batch reactions.     

Tumor necrosis factor-alpha enhances inhibitory effects of interleukin-1 beta on Leydig cell steroidogenesis

Human recombinant tumor necrosis factor-alpha (rTNF alpha) alone (up to 1000 units/ml) did not alter either basal or human chorionic gonadotropin (hCG)-induced testosterone formation in primary culture of rat Leydig cells. However, concomitant addition of rTNF alpha with human recombinant interleukin-1 beta (rIL-1 beta) enhanced the inhibitory effects of rIL-1 beta. The rIL-1 beta dose response curve was shifted to the left (IC50 changed from 1 ng/ml to 0.3 ng/ml). Even though rTNF alpha had no effect on testosterone formation, hCG-stimulated cyclic AMP formation was inhibited by rTNF alpha in a dose dependent manner. In the presence of both rTNF alpha and rIL-1 beta, hCG-induced cyclic AMP formation and binding of [125I]-hCG to Leydig cells were further inhibited. Testicular macrophages represent about 20% of the interstitial cells. TNF alpha and IL-1 may be produced locally by interstitial macrophages and have paracrine effects on Leydig cell function.