Endothelial dysfunction occurs in obese patients and high-fat diet (HFD) fed experimental animals. While geraniol has been reported to ameliorate inflammation and oxidative stress, inhibit tumor cell proliferation, and improve atherosclerosis, its direct effect on endothelial function remains uncharacterized. The present study therefore investigated the effect of geraniol on endothelial function in HFD mice and its underlying mechanisms. C57 BL/6 mice were fed an HFD (n = 40) or a normal diet (n = 20) for 8 weeks. HFD fed mice then were randomized to intraperitoneal treatment with geraniol (n = 20) or vehicle (n = 20) for another 6 weeks. Acetylcholine (Ach)-induced endothelial dependent vasorelaxation was measured on wire myography; reactive oxygen species (ROS) generation was assessed by fluorescence imaging, and NADPH oxidases (NOXs) and adhesive molecules VCAM-1 and ICAM-1 protein expression by western blotting. Geraniol improved endothelial function in HFD fed mice, as evidenced by its: 1. restoring endothelial dependent vasorelaxation induced by Ach, and reversing increased VCAM-1 and ICAM-1 expression; 2. attenuating HFD induced increased serum TBARS and aortic ROS generation; and 3. downregulating aortic NOX-2 expression in both HFD fed mice and in palmitic acid treated endothelial cells. Geraniol therefore protects against endothelial dysfunction induced by HFD through reducing NOX-2 associated ROS generation.Read more
This is the premier study reporting the remediation of atrazine contaminated soil with steel converter slag (SCS) catalyzed Fenton-like process. The effects of various operating parameters, such as SCS loads and H2O2 concentrations were evaluated with respect to the removal efficiency of atrazine. Results show the optimal SCS load and H2O2 concentration were 80gkg(-1) and 10%, respectably. The graded modified Fenton's oxidation with a 3-time addition of 10% H2O2 was able to remove 93.7% of total atrazine in the contaminated soil and maintain soil temperature within 50°C. In contrast to traditional Fenton treatment, a slight pH increase has been observed due to the addition of SCS. More importantly, experiment conducted at natural conditions with SCS gave the similar atrazine removal to the experiments with the other catalysts (e.g., FeSO4 and Fe2O3). One thing should be noted that after the treatment, dissolved organic carbon (DOC) content increased to 1.206gkg(-1) from an initial value of 0.339gkg(-1).Read more
Analogues of the natural product gallinamide A were prepared to elucidate novel inhibitors of the falcipain cysteine proteases. Analogues exhibited potent inhibition of falcipain-2 (FP-2) and falcipain-3 (FP-3) and of the development of Plasmodium falciparum in vitro. Several compounds were equipotent to chloroquine as inhibitors of the 3D7 strain of P. falciparum and maintained potent activity against the chloroquine-resistant Dd2 parasite. These compounds serve as promising leads for the development of novel antimalarial agents.Read more
To determine functional and structural alterations of peritoneum and fibrotic cytokines expression in peritoneal dialysis (PD) rats.
28 Sprague-Dawley (S-D) rats were randomly divided into four groups and dialyzed with various solutions daily for four weeks: (1) no solution (CON group), (2) 0.9% Saline solution (NS group), (3) 1.5% Dianeal (LG group), (4) 4.25% Dianeal (HG group). Peritoneal equilibration tests, ultrafiltration function and effluent protein quantification were measured. Peritoneum morphology was studied and immunohistochemistry were performed for detection of transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF), and fibronectin (FN) proteins. Reverse transcriptional-polymerase chain reaction was used to analyze the expression of TGF-β1, CTGF mRNA.
Administration of 4.25% Dianeal caused functional and structural changes of peritoneum, including protein loss through the transport process, decrease of peritoneal solute transport rate and ultrafiltration capacity. The collagen of peritoneum in the HG group was thicker than the other groups. The levels of CTGF, TGF-β1, and FN proteins were significantly the highest in the HG group, followed by the LG group. The liner correlation analysis showed positive correlations between the levels of CTGF, TGF-β1, and FN proteins and the collagen thickness. The expression of TGF-β1 and CTGF mRNA in the HG group were significantly higher than those in the other groups and were indicated positive correlation.
Using high glucose peritoneal dialysis solutions in rats may not only lead to processing of peritoneal fibrosis, which is promoted by ectopic expression of TGF-β1, but also increase the expression of CTGF. CTGF is an important fibrotic media of peritoneal fibrosis in PD rats.Read more
Endothelial-to-mesenchymal transition (EndoMT) has been recognized as a major reason for the pulmonary artery remodeling (PAR) in pulmonary artery hypertension (PAH). However, the molecular mechanisms and regulatory pathways involved in the EndoMT remain undefined. In the present study, we have confirmed that EndoMT was occurred in pulmonary arteries of rats induced by hypoxia and monocrotaline and in hypoxic pulmonary artery endothelial cells (PAECs). Moreover, hypoxia increased the expression of platelet-derived growth factor (PDGF) and transforming growth factor-β1 (TGF-β1) and decreased the expression of neprilysin (NEP), which contributed to the hypoxia-induced EndoMT of PAECs. Furthermore, a reciprocal regulation of PDGF-B and TGF-β1 induced by decreasing NEP promoted the EndoMT of PAECs under hypoxia, which was a novel molecular mechanism to reveal the EndoMT participating in PAR. More importantly, imatinib, a PDGF receptor antagonist, relieved PAR and EndoMT in PAH rats. Thus, our results identify a novel mechanism to reveal the formation of EndoMT in PAH, and imply that imatinib may serve as a new therapeutic approach for treatment of the third cardiovascular disease.Read more
To study the clinical effects of the adjustable external fixation combined with the limited internal fixation such as ordinary screws, Kirschner wire fixation for the treatment of complex calcaneal fractures (Sanders III, IV).
From January 2003 to June 2008, 27 patients 36 feet (19 feet in the left and 17 feet in the right) with calcaneal fractures of Sanders III and IV (the age ranged from 17 to 65 years, mean 37 years)were treated with external fixator combined with ordinary screws and Kirschner wire fixation. All the patients were undergone X-ray and CT examinations and classified by Crosby-Fitzgibbons-Sanders. The changes of the Böhler and Gissane angles were analyzed by X-ray. The functional of the feet was assessed by ZHANG Tie-liang calcaneal fractures scoring system.
Thirty-two feet were followed up for 11 to 24 months, with an average of 13 months. The Böhler and Gissane angles changed from average (8.0 +/- 7.3) degree and (130.5 +/- 10.5) degree, back to postoperative (29.6 +/- 7.4) degree and (122.5 +/- 8.6) degree. According to ZHANG Tie-liang scoring system, the result was excellent in 17 feet, good in 8 feet,fair in 5 feet and not satisfied with 2 feet. Three feet with wound infection or skin flap necrosis were healed after vacuum sealing drainage or wound dressing.
The combination of external fixator and limited internal fixation is an effective treatment for complex calcaneal fractures with few complications and good functional recovery.Read more
Pain greatly affects the quality of life of people worldwide. Despite their demonstrated efficacy, currently used opioid drugs and nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently associated with several adverse events. The identification of new therapeutic targets and the development of corresponding analgesics may represent novel approaches for effectively treating pain. SY0916 is a novel compound that was designed and synthesized by the Institute of Materia Medica, Chinese Academy of Medical Sciences. As demonstrated by the hot plate test, tail-flick test and the formalin test, SY0916 exerted strong peripheral and central antinociceptive effects. Western blot, immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) results indicate that SY0916 induces its peripheral antinociceptive effect by suppressing the peripheral activity of inflammatory mediators such as prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α) and 5-hydroxytryptamine (5-HT). Moreover, its central antinociceptive effect might be mediated by the down-regulation of PGE2 and TNF-α expression and the inhibition of p-p38 and NF-κB pathway signaling in glial cells. These findings demonstrate that SY0916 may serve as a promising analgesic candidate drug.Read more
KGLP-1, a 31-amino acid glucagon-like peptide-1 (GLP-1) analogue, has a great therapeutic potential for anti-diabetes. In this work, a strategy for expression and purification of functional KGLP-1 peptide has been established. KGLP-1 cDNA was fused with glutathione S-transferase (GST), with an enterokinase cleavage site in the fusion junction. The recombinant fusion protein GST-KGLP-1 was affinity purified via the GST-tag, and then digested with enterokinase. The resulting GST part as well as the enzymes were eliminated by ultra-filtration followed by size exclusion chromatograph. The yield of purified KGLP-1 was approximately 12.1 mg/L, with purity of 96.18 %. The recombinant KGLP-1 was shown to have similar bioactivity as native GLP-1 when evaluated in a Chinese hamster ovary cell line expressing a GLP-1 receptor-egfp reporter gene.Read more
A novel visible-light photoelectrochemical (PEC) biosensor based on localized surface plasmon resonance (LSPR) enhancement and dye sensitization was fabricated for highly sensitive analysis of protein kinase activity with ultralow background. In this strategy, DNA conjugated gold nanoparticles (DNA@AuNPs) were assembled on the phosphorylated kemptide modified TiO2/ITO electrode through the chelation between Zr(4+) ions and phosphate groups, then followed by the intercalation of [Ru(bpy)3](2+) into DNA grooves. The adsorbed [Ru(bpy)3](2+) can harvest visible light to produce excited electrons that inject into the TiO2 conduction band to form photocurrent under visible light irradiation. In addition, the photocurrent efficiency was further improved by the LSPR of AuNPs under the irradiation of visible light. Moreover, because of the excellent conductivity and large surface area of AuNPs that facilitate electron-transfer and accommodate large number of [Ru(bpy)3](2+), the photocurrent was significantly amplified, affording an extremely sensitive PEC analysis of kinase activity with ultralow background signals. The detection limit of as-proposed PEC biosensor was 0.005 U mL(-1) (S/N = 3). The biosensor also showed excellent performances for quantitative kinase inhibitor screening and PKA activities detection in MCF-7 cell lysates under forskolin and ellagic acid stimulation. The developed dye-sensitization and LSPR enhancement visible-light PEC biosensor shows great potential in protein kinases-related clinical diagnosis and drug discovery.Read more
Development of exposure assessment model is the key component for epidemiological studies concerning air pollution, but the evidence from China is limited. Therefore, a linear mixed effects (LME) model was established in this study in a Chinese metropolis by incorporating aerosol optical depth (AOD), meteorological information and the land use regression (LUR) model to predict ground PM10 levels on high spatiotemporal resolution. The cross validation (CV) R(2) and the RMSE of the LME model were 0.87 and 19.2 μg/m(3), respectively. The relative prediction error (RPE) of daily and annual mean predicted PM10 concentrations were 19.1% and 7.5%, respectively. This study was the first attempt in China to estimate both short-term and long-term variation of PM10 levels with high spatial resolution in a Chinese metropolis with the LME model. The results suggested that the LME model could provide exposure assessment for short-term and long-term epidemiological studies in China.Read more