Rosiglitazone Attenuated Endothelin-1-Induced Vasoconstriction of Pulmonary Arteries in the Rat Model of Pulmonary Arterial Hypertension via Differential Regulation of ET-1 Receptors

Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a progressive increase in pulmonary arterial pressure leading to right ventricular failure and death. Activation of the endothelin (ET)-1 system has been demonstrated in plasma and lung tissue of PAH patients as well as in animal models of PAH. Recently, peroxisome proliferator-activated receptor γ (PPARγ) agonists have been shown to ameliorate PAH. The present study aimed to investigate the mechanism for the antivasoconstrictive effects of rosiglitazone in response to ET-1 in PAH. Sprague-Dawley rats were exposed to chronic hypoxia (10% oxygen) for 3 weeks. Pulmonary arteries from PAH rats showed an enhanced vasoconstriction in response to ET-1. Treatment with PPARγ agonist rosiglitazone (20 mg/kg per day) with oral gavage for 3 days attenuated the vasocontractive effect of ET-1. The effect of rosiglitazone was lost in the presence of L-NAME, indicating a nitric oxide-dependent mechanism. Western blotting revealed that rosiglitazone increased ETBR but decreased ETAR level in pulmonary arteries from PAH rats. ETBR antagonist A192621 diminished the effect of rosiglitazone on ET-1-induced contraction. These results demonstrated that rosiglitazone attenuated ET-1-induced pulmonary vasoconstriction in PAH through differential regulation of the subtypes of ET-1 receptors and, thus, provided a new mechanism for the therapeutic use of PPARγ agonists in PAH

Peroxisome Proliferator-Activated Receptor γ

Lipid phosphate phosphohydrolase 1 (LPP1), a membrane ectophosphohydrolase regulating the availability of bioactive lipid phosphates, plays important roles in cellular signaling and physiological processes such as angiogenesis and endothelial migration. However, the regulated expression of LPP1 remains largely unknown. Here, we aimed to examine a role of peroxisome proliferator-activated receptor γ (PPARγ) in the transcriptional control of LPP1 gene expression. In human umbilical vein endothelial cells (HUVECs), quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) demonstrated that activation of PPARγ increased the mRNA level of LPP1. Chromatin immunoprecipitation assay showed that PPARγ binds to the putative PPAR-responsive elements (PPREs) within the 5′-flanking region of the human LPP1 gene. Genomic fragment containing 1.7-kilobase of the promoter region was cloned by using PCR. The luciferase reporter assays demonstrated that overexpression of PPARγ and rosiglitazone, a specific ligand for PPARγ, could significantly upregulate the reporter activity. However, site-directed mutagenesis of the PPRE motif abolished the induction. In conclusion, our results demonstrated that PPARγ transcriptionally activated the expression of LPP1 gene in ECs, suggesting a potential role of PPARγ in the metabolism of phospholipids

Hydrothermal Synthesis of a Nanosized LiNi(0.5)Mn(1.5)O(4) Cathode Material for High Power Lithium-Ion Batteries

A LiNi(0.5)Mn(1.5)O(4) material for use as a 5 V spinel cathode for lithium-ion batteries was synthesized for the first time using a hydrothermal approach. The effects of the LiOH concentration and hydrothermal temperature on the hydrothermal products were investigated systematically, where the LiOH concentration (e.g., 1.1 M) was proven critical to successfully synthesize the 5 V spinel. At low LiOH concentrations (e.g., 0.8-1.0 M), the obtained products may be MnOOH, alpha-MnO(2), and 4 V spinel, while high concentrations (e.g., > 1.8 M) favor the Li(2)MnO(3) phase. The particle size of the as-prepared 5 V spinel is ca. 30 nm, and its formation is associated with the dissolution-recrystallization mechanism from an amorphous precursor. Cell tests show that the as-prepared LiNi(0.5)Mn(1.5)O(4) material obtained at 180 degrees C exhibits a capacity of ca. 100 mAh g(-1) at a current density of 28 mA g(-1), where ca. 60 mAh g(-1) above 4.2 V. Such a 5 V material shows an excellent rate capability with a capacity of ca. 73 mAh g(-1) delivered at 2800 mA g(-1), 73% of that obtained at 28 mA g(-1). (C) 2010 The Electrochemical Society. [DOI: 10.1149/1.3521292] All rights reserved.National Basic Research Program of China (973 Program)[2007CB209702]; National Natural Science Foundation of China[20873115, 20021002

Highly crystalline macroporous beta-MnO2: Hydrothermal synthesis and application in lithium battery

A highly crystalline macroporous beta-MnO2 was hydrothermally synthesized using stoichiometric reaction between KMnO4 and MnCl2. The as-prepared material has a pore size of ca. 400 nm and a shell thickness of 300-500 nm. The formation of the macroporous morphology is related to self-assembling from nanowires of alpha-MnO2, and could be obtained at high reactant concentrations (e.g., 0.8 M KMno(4)) but not at low ones (e.g., below 0.04M KMnO4). Compared to conventional bulk beta-MnO2 processing very low capacity, our macroporous material exhibits good electrochemical activity, e.g., obtaining an initial discharge capacity of 251 mAh g(-1) and sustaining as ca. 165 mAh g(-1) at 10 mA g(-1). The electrochemical activity of the as-prepared beta-MnO2 is related to its macroporous morphology and small shell thickness: the former leads to that electrolyte can flood pore of the material and its inner surface is available for lithium ion diffusion, while the latter helps to release the stress from phase transformation during the initial discharging. The X-ray diffraction characterizations of the macroporous beta-MnO2 electrodes suggest that, upon initial discharging, such a beta-MnO2 will be irreversibly transformed to an orthorhombic LixMnO2 and then cycled within the new developed phase in the subsequent lithium insertion/extraction processes. (C) 2010 Elsevier Ltd. All rights reserved.National Basic Research Program of China (973 Program) [2007CB209702]; National Natural Science Foundation of China [20473060, 29925310, 20021002

Does additional resection of a positive microscopic ductal margin benefit patients with perihilar cholangiocarcinoma: A systematic review and meta-analysis.

BACKGROUND:The incidence of a positive microscopic ductal margin (R1) after surgical resection for perihilar cholangiocarcinoma (pCCA) remains high, but the beneficial of additional resection has not been confirmed by any meta-analysis and randomized clinical trials (RCT), which also increased the risk of morbidity and mortality. Hence, a systematic review is warranted to evaluate the clinical value of additional resection of intraoperative R1 for pCCA. METHODS:Eligible studies were searched by PubMed, MedLine, Embase, the Cochrane Library, Web of Science, from Jan.1st 2000 to Nov.30th 2019, evaluating the 1-, 3-, and 5-year overall survival (OS) rates of additional resection of intraoperative pathologic R1 for pCCA. Odds ratio (OR) with 95% confidence interval (CI) was used to determine the effect size by a randomized-effect model. RESULTS:Eight studies were enrolled in this meta-analysis, including 179 patients in the secondary R0 group, 843 patients in the primary R0 group and 253 patients in the R1 group. The pooled OR for the 1-, 3-, and 5-year OS rate between secondary R0 group and primary R0 group were 1.03(95%CI 0.64~1.67, P = 0.90), 0.92(95%CI 0.52~1.64, P = 0.78), and 0.83(95%CI 0.37~1.84, P = 0.65), respectively. The pooled OR for the 1-, 3-, and 5-year OS rate between secondary R0 group and R1 group were 2.14(95%CI 1.31~3.50, P = 0.002), 2.58(95%CI 1.28~5.21, P = 0.008), and 3.54(95%CI 1.67~7.50, P = 0.001), respectively. However, subgroup analysis of the West showed that the pooled OR for the 1-, and 3-year OS rate between secondary R0 group and R1 group were 2.05(95%CI 0.95~4.41, P = 0.07), 1.91(95%CI 0.96~3.81, P = 0.07), respectively. CONCLUSION:With the current data, additional resection should be recommended in selected patients with intraoperative R1, but the conclusion is needed further validation

Burden of road traffic accidents in Nepal by calculating disability-adjusted life years

Objective: To calculate the burden of road traffic accidents in Kathmandu Valley and then extrapolate this to the national level. Methods: A prospective study was performed to compute the burden of road traffic accidents by quantification of disability-adjusted life years (DALYs) using the Global Burden of Disease Study method on the basis of 1-year data from nine hospitals in Nepal and the Department of Forensic Medicine and cross-checked with the Nepal Traffic Directorate. Multiple methods were applied to the extrapolated population metrics of the burden of road traffic accidents in Nepal. Results: The total number of years of life lived in disability, years of life lost, and DALYs in Nepal were 38,848±194, 119,935±1464, and 158,783±1658 (95% confidence interval) respectively. The number of years lost because of morbidity and death was similar in Kathmandu Valley. Most (75%) of the DALYs resulted from years of life lost in Nepal. Males accounted for 73% of DALYs. Almost half (44%) of the DALYs were contributed by the group aged 15–29 years. Conclusion: This study is the first to calculate the burden of road traffic accidents in Nepal using Nepal’s own data. Nepal needs to develop and enhance its own system to identify significant public health issues so as to set national priorities for prevention of road traffic accidents

Adipocyte-specific loss of PPARγ attenuates cardiac hypertrophy

Adipose tissue is a key endocrine organ that governs systemic homeostasis. PPARγ is a master regulator of adipose tissue signaling that plays an essential role in insulin sensitivity, making it an important therapeutic target. The selective PPARγ agonist rosiglitazone (RSG) has been used to treat diabetes. However, adverse cardiovascular effects have seriously hindered its clinical application. Experimental models have revealed that PPARγ activation increases cardiac hypertrophy. RSG stimulates cardiac hypertrophy and oxidative stress in cardiomyocyte-specific PPARγ knockout mice, implying that RSG might stimulate cardiac hypertrophy independently of cardiomyocyte PPARγ. However, candidate cell types responsible for RSG-induced cardiomyocyte hypertrophy remain unexplored. Utilizing cocultures of adipocytes and cardiomyocytes, we found that stimulation of PPARγ signaling in adipocytes increased miR-200a expression and secretion. Delivery of miR-200a in adipocyte-derived exosomes to cardiomyocytes resulted in decreased TSC1 and subsequent mTOR activation, leading to cardiomyocyte hypertrophy. Treatment with an antagomir to miR-200a blunted this hypertrophic response in cardiomyocytes. In vivo, specific ablation of PPARγ in adipocytes was sufficient to blunt hypertrophy induced by RSG treatment. By delineating mechanisms by which RSG elicits cardiac hypertrophy, we have identified pathways that mediate the crosstalk between adipocytes and cardiomyocytes to regulate cardiac remodeling

Road Traffic Accident and its Characteristics in Kathmandu Valley

Introduction: Road traffic accident is alarming in Nepal. The objective of this research is to find out the characteristics of RTA in central part of Nepal. Methods: A prospective descriptive study was taken from 1 August 2014 to 31 July 2015. Data were collected from postmortem department and nine hospitals in Kathmandu Valley. Inventory sheets with targeted variables for secondary sources were created. Results: A total of 3461 morbidity cases from hospitals and 265 mortality cases from postmortem department were included in this study. The ratio of male victim to female was 2.3:1. Around 75% of victims were between 15-49 years old. Pedestrians were the most vulnerable (33%) followed by riders of motorized 2-3 wheelers. Two wheeler motorized vehicles were most frequently (67.2%)involved in RTAs. More RTA occurred on daytime, Saturdays, July and November. Around half of the victims did not arrive in hospitals in one hour. The most common injury type was soft tissue injury (37.6%), followed by open wound (20.9%), fracture (18%) and traumatic brain injuries (12.7%). Conclusions: According to the characteristic of RTA found in this study, following preventive measures are recommended Helmet was necessary for two wheeled backseat riders. Road safety education towards age group of 15-49 was compulsory. Precaution should neither be omitted regarding road safety on weekends, holidays, nor in rainy and festival season. Future studies could be focused on estimation of burden of disease caused by RTA and its determinants in Nepal. Keywords: injury; Nepal; road traffic accident; road safety. | PubMe