Pioglitazone Attenuates Vascular Fibrosis in Spontaneously Hypertensive Rats

Objective. We sought to investigate whether the peroxisome proliferator-activated receptor-γ (PPAR-γ) ligand pioglitazone can attenuate vascular fibrosis in spontaneously hypertensive rats (SHRs) and explore the possible molecular mechanisms. Methods. SHRs (8-week-old males) were randomly divided into 3 groups (n = 8 each) for treatment: pioglitazone (10 mg/kg/day), hydralazine (25 mg/kg/day), or saline. Normal male Wistar Kyoto (WKY) rats (n = 8) served as normal controls. Twelve weeks later, we evaluated the effect of pioglitazone on vascular fibrosis by Masson's trichrome and immunohistochemical staining of collagen III and real-time RT-PCR analysis of collagen I, III and fibronectin mRNA.Vascular expression of PPAR-γ and connective tissue growth factor (CTGF) and transforming growth factor-β (TGF-β) expression were evaluated by immunohistochemical staining, western blot analysis, and real-time RT-PCR. Results. Pioglitazone and hydralazine treatment significantly decreased systolic blood pressure in SHRs. Masson's trichrome staining for collagen III and real-time RT-PCR analysis of collagen I, III and fibronectin mRNA indicated that pioglitazone significantly inhibited extracellular matrix production in the aorta. Compared with Wistar Kyoto rats, SHRs showed significantly increased vascular CTGF expression. Pioglitazone treatment significantly increased PPAR-γ expression and inhibited CTGF expression but had no effect on TGF-β expression. Conclusions. The results indicate that pioglitazone attenuated vascular fibrosis in SHRs by inhibiting CTGF expression in a TGF-β-independent mechanism

Genetic Engineering of Starch Biosynthesis in Maize Seeds for Efficient Enzymatic Digestion of Starch during Bioethanol Production

Maize accumulates large amounts of starch in seeds which have been used as food for human and animals. Maize starch is an importantly industrial raw material for bioethanol production. One critical step in bioethanol production is degrading starch to oligosaccharides and glucose by alpha-amylase and glucoamylase. This step usually requires high temperature and additional equipment, leading to an increased production cost. Currently, there remains a lack of specially designed maize cultivars with optimized starch (amylose and amylopectin) compositions for bioethanol production. We discussed the features of starch granules suitable for efficient enzymatic digestion. Thus far, great advances have been made in molecular characterization of the key proteins involved in starch metabolism in maize seeds. The review explores how these proteins affect starch metabolism pathway, especially in controlling the composition, size and features of starch. We highlight the roles of key enzymes in controlling amylose/amylopectin ratio and granules architecture. Based on current technological process of bioethanol production using maize starch, we propose that several key enzymes can be modified in abundance or activities via genetic engineering to synthesize easily degraded starch granules in maize seeds. The review provides a clue for developing special maize cultivars as raw material in the bioethanol industry

Synthesis, crystal structure, luminescent, and photocatalytic properties of a uranyl(VI)-organic framework based on tripodal flexible zwitterionic ligand

1409-1415The uranyl-organic framework based tripodal flexible zwitterion ligand 1,1',1''-[benzene-1,3,5-triyltris(methylene)] tris(pyridine-4-carboxylic acid) tribromine (H3LBr3), [(UO2)2(μ3-O)(μ2-OH)L]NO3·nH2O (n ≈ 5) (1) has been synthesized under hydrothermal condition and characterized by elemental analysis, IR spectroscopy, single-crystal X-ray diffraction, powder X-ray diffraction, thermogravimetric analysis, and UV-visible spectroscopy. Compound 1 contains a tetra-uranyl oxo-cluster, which displays a microporous 3D structure. The fluorescence measurement shows that 1 exhibits strong luminescence. Furthermore, 1 shows good photocatalytic activity for the degradation of methylene blue

HCV core protein inhibits polarization and activity of both M1 and M2 macrophages through the TLR2 signaling pathway

Hepatitis C virus (HCV) establishes persistent infection in most infected patients, and eventually causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma in some patients. Monocytes and macrophages provide the first line of defense against pathogens, but their roles in HCV infection remains unclear. We have reported that HCV core protein (HCVc) manipulates human blood-derived dendritic cell development. In the present study, we tested whether HCVc affects human blood-derived monocyte differentiating into macrophages. Results showed that HCVc inhibits monocyte differentiation to either M1 or M2 macrophages through TLR2, associated with impaired STATs signaling pathway. Moreover, HCVc inhibits phagocytosis activity of M1 and M2 macrophages, M1 macrophage-induced autologous and allogeneic CD4+ T cell activation, but promotes M2 macrophage-induced autologous and allogeneic CD4+ T cell activation. In conclusion, HCVc inhibits monocyte-derived macrophage polarization via TLR2 signaling, leading to dysfunctions of both M1 and M2 macrophages in chronic HCV infected patients. This may contribute to the mechanism of HCV persistent infection, and suggest that blockade of HCVc might be a novel therapeutic approach to treating HCV infection

Assessment Accuracy of Standard Point Positioning Enhanced by Observation and Position Domain Filtering Utilizing a Multi-Epoch Least-Squares Integration Method

To enhance the positioning accuracy of standalone GNSS receivers in environments unable to provide precise ephemeris and clock offset, such as undeveloped forest areas that lack network communication and power supply, this study employed the Time Difference Carrier Phase (TDCP) technology to improve the positioning accuracy of Standard Point Positioning (SPP), where the Least-Squares (LS) and the extended Multi-Epoch Least Squares (MELS) method were applied in the position domain filtering for a single GNSS receiver and compare its performance with the existing observation domain filtering method. Firstly, the simulated data sets with various positioning accuracies were used to verify the effectiveness and convergence of the LS filtering methods. The results indicate that the LS filtering method produces a lower root mean square (RMS) error than the original strategy. Secondly, this study uses two kinematic GNSS data sets to evaluate the performance of the observation and position domain filtering, with an emphasis on the MELS method. The numerical experiment results show that the position domain LS filtering method outperforms the other two methods. The open environment experiments result shows that the positioning domain filtering method achieved positioning accuracies of 0.202 m, 0.843 m, and 2.036 m in the E, N, and U directions, respectively, with improvements of 68.0%, 21.6%, and 24.0%, compared to the original algorithm which achieved positioning accuracies of 0.631 m, 1.076 m, and 2.680 m. It also achieved improvements of 24.0%, 4.0%, and 18.3%, respectively, compared to the observation domain filtering method with positioning accuracies of 0.353 m, 0.886 m, and 2.526 m. The forest scenes experiments result shows that the positioning domain filtering method achieved positioning accuracies of 1.308 m, 1.375 m, and 2.133 m in the E, N, and U directions, respectively, with improvements of 42.4%, 36.2%, and 27.6%, compared to original algorithm which achieved positioning accuracies of 1.863 m, 1.873 m, and 2.722 m, and also achieved improvements of 27.0%, 19.4% and 10.6%, respectively, comparing to observation domain filtering method with positioning accuracies of 1.661 m, 1.642 m and 2.359 m. Moreover, the examination of the LS method results based on different epochs reveals that the filtering accuracy increases as more epochs are incorporated into the position domain integration and the enhancement value reaches a few millimeters

Cardioprotective Effect of Beta-3 Adrenergic Receptor Agonism Role of Neuronal Nitric Oxide Synthase

ObjectivesThe aim of this study was to determine whether activation of β3-adrenergic receptor (AR) and downstream signaling of nitric oxide synthase (NOS) isoforms protects the heart from failure and hypertrophy induced by pressure overload.Backgroundβ3-AR and its downstream signaling pathways are recognized as novel modulators of heart function. Unlike β1- and β2-ARs, β3-ARs are stimulated at high catecholamine concentrations and induce negative inotropic effects, serving as a “brake” to protect the heart from catecholamine overstimulation.MethodsC57BL/6J and neuronal NOS (nNOS) knockout mice were assigned to receive transverse aortic constriction (TAC), BRL37344 (β3 agonist, BRL 0.1 mg/kg/h), or both.ResultsThree weeks of BRL treatment in wild-type mice attenuated left ventricular dilation and systolic dysfunction, and partially reduced cardiac hypertrophy induced by TAC. This effect was associated with increased nitric oxide production and superoxide suppression. TAC decreased endothelial NOS (eNOS) dimerization, indicating eNOS uncoupling, which was not reversed by BRL treatment. However, nNOS protein expression was up-regulated 2-fold by BRL, and the suppressive effect of BRL on superoxide generation was abrogated by acute nNOS inhibition. Furthermore, BRL cardioprotective effects were actually detrimental in nNOS–/– mice.ConclusionsThese results are the first to show in vivo cardioprotective effects of β3-AR–specific agonism in pressure overload hypertrophy and heart failure, and support nNOS as the primary downstream NOS isoform in maintaining NO and reactive oxygen species balance in the failing heart