Comparison of P25 and nanobelts on Kruppel-like factor-mediated nitric oxide pathways in human umbilical vein endothelial cells

Recently, we reported that titanium dioxide (TiO₂) materials activated endothelial cells via Kruppel-like factor (KLF)-mediated nitric oxide (NO) dysfunction, but the roles of physical properties of materials are not clear. In this study, we prepared nanobelts from P25 particles and compared their adverse effects to human umbilical vein endothelial cells (HUVECs). TiO₂ nanobelts had belt-like morphology but comparable surface areas as P25 particles. When applied to HUVECs, P25 particles or nanobelts did not induce cytotoxicity, although nanobelts were much more effective to increase intracellular Ti element concentrations compared the same amounts of P25 particles. Only nanobelts significantly induced THP-1 adhesion onto HUVECs. Consistently, nanobelts were more significant to induce the expression of intracellular adhesion molecule-1 (ICAM1) and the release of soluble ICAM-1 (sICAM-1), indicating that nanobelts were more potent to induce endothelial activation in vitro. As the mechanisms for endothelial activation, both P25 and nanobelts reduced the generation of intracellular NO as well as the expression of NO regulators KLF2 and KLF4. Combined, the results from this study indicated that the different morphologies of P25 particles and nanobelts only changed their internalization into HUVECs but showed minimal impact on KLF-mediated NO signaling pathways.     

Metal Phosphate-Supported Pt Catalysts for CO Oxidation

Oxides (such as SiO₂, TiO₂, ZrO₂, Al₂O₃, Fe₂O₃, CeO₂) have often been used to prepare supported Pt catalysts for CO oxidation and other reactions, whereas metal phosphate-supported Pt catalysts for CO oxidation were rarely reported. Metal phosphates are a family of metal salts with high thermal stability and acid-base properties. Hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂, denoted as Ca-P-O here) also has rich hydroxyls. Here we report a series of metal phosphate-supported Pt (Pt/M-P-O, M = Mg, Al, Ca, Fe, Co, Zn, La) catalysts for CO oxidation. Pt/Ca-P-O shows the highest activity. Relevant characterization was conducted using N₂ adsorption-desorption, inductively coupled plasma (ICP) atomic emission spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), CO₂ temperature-programmed desorption (CO₂-TPD), X-ray photoelectron spectroscopy (XPS), and H₂ temperature-programmed reduction (H₂-TPR). This work furnishes a new catalyst system for CO oxidation and other possible reactions.     

Ammonia metabolism,the brain and fatigue; revisiting the link

This review addresses the ammonia fatigue theory in light of new evidence from exercise and disease studies and aims to provide a view of the role of ammonia during exercise. Hyperammonemia is a condition common to pathological liver disorders and intense or exhausting exercise. In pathology, hyperammonemia is linked to impairment of normal brain function and the onset of the neurological condition, hepatic encephalopathy. Elevated blood ammonia concentrations arise due to a diminished capacity for removal via the liver and lead to increased exposure of organs, such as the brain, to the toxic effects of ammonia. High levels of brain ammonia can lead to deleterious alterations in astrocyte morphology, cerebral energy metabolism and neurotransmission, which may in turn impact on the functioning of important signalling pathways within the neuron. Such changes are believed to contribute to the disturbances in neuropsychological function, in particular the learning, memory, and motor control deficits observed in animal models of liver disease and also patients with cirrhosis. Hyperammonemia in exercise occurs as a result of an increased production by contracting muscle, through adenosine monophosphate (AMP) deamination (the purine nucleotide cycle) and branched chain amino acid (BCAA) deamination prior to oxidation. Plasma concentrations of ammonia during exercise often achieve or exceed those measured in liver disease patients, resulting in increased cerebral uptake. In this article we propose that exercise-induced hyperammonemia may lead to concomitant disturbances in brain function, potentially through similar mechanisms underpinning pathology, which may impact on performance as fatigue or reduced function, especially during extreme exercise.     

金水宝胶囊联合依帕司他治疗糖尿病肾病的临床研究

目的探讨金水宝胶囊联合依帕司他片治疗糖尿病肾病的临床疗效。方法选取2014年9月—2017年4月商丘市第一人民医院收治的糖尿病肾病患者172例,随机分为对照组和治疗组,每组各86例。对照组口服依帕司他片,50 mg/次,1次/d。治疗组在对照组治疗的基础上口服金水宝胶囊,3粒/次,3次/d。两组患者均连续治疗8周。观察两组的临床疗效,比较两组的血糖、肾功能指标、24 h尿微量蛋白定量、血清氧化指标和血清抗氧化指标。结果治疗后,对照组和治疗组的总有效率分别为75.6%、93.0%,两组比较差异有统计学意义(P0.05)。治疗后,两组空腹血糖、糖化血红蛋白水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组血糖指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清肌酐(Scr)、尿素氮(BUN)、胱抑素C(Cys-C)、血清β2微球蛋白(β2-MG)、24 h尿微量蛋白定量、尿蛋白排泄率(UAER)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组活性氧(ROS)、脂质过氧化氢(LHP)和晚期蛋白氧化产物(AOPPS)水平均显著下降,同组治疗前后比较差异有统计学意义(P0.05);且治疗组血清氧化指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组超氧化物歧化酶(SOD)、维生素E(VitE)、维生素C(VitC)和总抗氧化能力(T-AOC)水平均显著升高,同组治疗前后比较差异有统计学意义(P0.05);且治疗组血清抗氧化指标明显高于对照组,两组比较差异具有统计学意义(P0.05)。结论金水宝胶囊联合依帕司他片治疗糖尿病肾病具有较好的临床疗效,可改善肾功能,增强抗氧化能力,降低氧化反应,具有一定临床推广应用价值。     

二烯丙基三硫醚对脂多糖诱导小鼠肺炎的改善作用

目的探讨二烯丙基三硫醚(DATS)对脂多糖(LPS)诱导的小鼠肺炎的改善作用,并探讨其作用机制。方法小鼠随机分为对照组、模型组及DATS 20、40、80 mg/kg预防组和DATS 20、40、80 mg/kg治疗组。通过ip LPS制备小鼠急性肺炎模型,考察DATS对血清生化指标丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)、炎症因子一氧化氮(NO)、细胞白介素8(IL-8)和肿瘤坏死因子α(TNF-α)、肺组织中髓过氧化物酶(MPO)、NO、NF-κB p65的影响。结果 DATS 40、80 mg/kg预防组和DATS 40、80 mg/kg治疗组能显著降低AST、NO、IL-8和TNF-α水平(P0.05),DATS 80 mg/kg预防组和DATS 80 mg/kg能显著降低LDH水平(P0.05),显著升高SOD水平(P0.05)。DATS 80 mg/kg预防组和DATS 80 mg/kg治疗组能显著升高MPO和NO水平(P0.05),并能抑制NF-κB p65的转移。结论 DATS对LPS诱导的肺部氧化损伤和炎症反应有一定的逆转作用,与DATS抑制NF-κB核转移和MPO活性有关。     

New dianthramide and cinnamic ester glucosides from the roots of Aconitum carmichaelii

Four new compounds N-salicyl-3-hydroxyanthranilic acid methyl ester (1), N-(2′-dehydroxysalicyl)-3-hydroxyanthranilic acid methyl ester (2), methyl-4-β-D-allopyranosyl-ferulate (3), and methyl-4-β-D-gulopyranosyl-cinnamate (4), along with six known compounds (5–10), were isolated from the roots of Aconitum carmichelii Debx. Their structures were elucidated on the basis of spectral data analysis, including 1D, 2D-NMR, and HR-ESI-MS. Compounds 1 and 2 showed the inhibition of nitric oxide (NO) production with IC₅₀ values of 9.13 and 19.94 μM, respectively.     

Prediction of regioselectivity and preferred order of metabolisms on CYP1A2-mediated reactions part 3: Difference in substrate specificity of human and rodent CYP1A2 and the refinement of predicting system

Differences in CYP1A2-mediated metabolisms in human, rat and mouse have been analyzed with Template of human CYP1A2 established in our previous studies (Drug Metab Pharmacokinet 31:363, 2016 and 32:229, 2017). Using more than 25 chemicals including phenanthrene, MeIQx, PhIP, caffeine and furafylline, Template for human CYP1A2 was found to be applicable for rat and mouse CYP1A2 reactions with the consideration of five distinct regional interactions: 1) Expanded use of Ring D region of pro-metabolized molecules and also of trigger molecules, 2) acceptance of secondary amino groups at Position 31 of Ring eC1, 3) overlapping of pro-metabolized and trigger molecules at Ring eC4, 4) restricted maneuvering of substrates into Bay 1 region, and 5) allowance of passage of slightly large ligands in Thin-Area. These distinction points were found to be mutual for both substrates and inhibitors. In the present study, the decision-tree for substrates entering from Thin-Area has been reevaluated in consideration of species differences in human and rodent CYP1A2 forms. As the results, five steps of verification procedures have been introduced to predict the occurrence order of the regioselective metabolisms.     

The effect of medical treatment on nasal exhaled nitric oxide (NO) in patients with persistent allergic rhinitis: A randomized control study

PurposeThis study aimed to evaluate the role of nasal nitric oxide (NO) in the management of patients with persistent allergic rhinitis (PER).MethodsIt was a randomized and comparative study. The study subjects were classified as controls (healthy subjects) or patients with PER based on defined criteria. All clinical, functional and biological data were collected for analyzing. Nasal fractional exhaled nitric oxide (FENO) was measured by electroluminescence device. Patients with PER were randomized for treatment with antihistamine (ATH) combined with leukotriene receptor antagonists (LRA) or only with intranasal steroids (INS).ResultsDuring two years, 501 subjects were included: 234 control subjects and 267 patients with PER. The levels of nasal NO, total IgE, blood eosinophil counts, and apnea-hypopnea index (AHI) in patients with PER were higher than controls (P < 0.001; P < 0.05; P < 0.05; P < 0.01; respectively). There were statistically significant correlations between nasal NO, nasal peak flows, total IgE, and blood eosinophil counts in patients with PER (R = −0.687 and P = 0.0012; R = −0.643 and P = 0.0018; R = 0.432 and P = 0.0024; R = 0.445 and P = 0.002; respectively). After 6 months of treatment, patients treated with INS had greater improvement of clinical symptoms and reduction of nasal NO values than patients treated with ATH + LRA (985 ± 253 vs. 732 ± 298 ppb; P < 0.05).ConclusionNasal NO measurement is a useful tool for the follow-up of patients with PER. It also helps clinicians to estimate the level of response to treatment in patients with PER.     

Selective modulation of endogenous nitric oxide formation in ischemia/reperfusion injury in isolated rat hearts

The role of nitric oxide (NO) in ischemia/reperfusion injury is controversial. We tested the role of inducible NOS (iNOS) in the ischemia/reperfusion injury in isolated rat hearts using the selective iNOS inhibitor S-methylisothiourea sulfate (SMT) and the non-selective NOS inhibitor N^G-nitro-L-arginine methyl ester (L-NAME). After 15 min of stabilization in Langendorff mode, hearts were perfused either with normal Krebs-Henseleit buffer, buffer containing 100 μM L-NAME, 0.5 μM SMT or 50 μM SMT for 5 min and were subjected to 25 min of ischemia followed by 30 min of reperfusion. Left ventricular developed pressure (LVDP) and total coronary flow (CF) were recorded continuously. After ischemia/reperfusion, a marked expression of iNOS protein was demonstrated by Western blotting, while virtually no iNOS protein was present in hearts without ischemia/reperfusion. Regional myocardial blood flow (RMBF) was measured with colored microspheres. Coronary vasoactive concentration of L-NAME and SMT depressed myocardial function as shown by decreased LVDP, dP/dt_max and coronary .ow before ischemia. After ischemia the recovery of the total CF was impaired in L-NAME and 50 μM SMT pretreated hearts which was related to homogenous RMBF decrease in the right and left ventricle compared to that in control group. Low concentration SMT (0.5 μM) showed no coronary vasoactive effects before ischemia and attenuated ischemia/reperfusion injury indicated by lower ischemic contracture at 25 min of ischemia and reduced CK and LDH release during reperfusion. Thus, NOS inhibition did not affect blood flow distribution in rat hearts either in the pre-ischemic or reperfusion period. Selective iNOS inhibition reduced ischemic injury by reducing ischemic contracture and CK as well as LDH release during reperfusion. Received: 20 March 2002, Returned for 1. revision: 8 April 2002, 1. Revision received: 14 August 2002, Returned for 2. revision: 5 September 2002, 2. Revision received: 3 February 2003, Accepted: 18 February 2003, Published online: 16 April 2003     

Anti-Inflammatory Properties of HDL

Reviews in Endocrine and Metabolic Disorders -