Organophosphorus nerve agent (OPNA) adducts to butyrylcholinesterase (BChE) can be applied to confirm exposure in humans. A sensitive method for generic detection of G- and V-series OPNA adducts to BChE in plasma was developed by combining an improved procainamide-gel separation (PGS) and pepsin digestion protocol with ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Residual matrix interferences from prior PGS purification of OPNA-BChE adducts from plasma were found to be a critical cause of significantly reduced UHPLC-MS/MS detection sensitivity.
View Article and Find Full Text PDFSorafenib (SF), a multi-kinase inhibitor, is the first FDA-approved systemic chemotherapy drug for advanced hepatocellular carcinoma (HCC). However, its clinical application is limited by severe toxicity and side effects associated with high applied doses. Sophora alopecuroides L.
View Article and Find Full Text PDFCerebral aneurysm (CA) is a common brain disease, and the development of cerebral aneurysm is driven by inflammation and hemodynamic stress. MicroRNA (miR)-124-5p is reported to be associated with inflammatory response in brain disease such as cerebral ischemia-reperfusion injury. However, the function and molecular mechanism of miR-124-5p in CA are not clear, thus, the effects of miR-124-5p on inflammatory response in CA were explored.
View Article and Find Full Text PDFIn order to discover antiplatelet drug with novel structure and expand our research scope, total twenty 1,3-benzenedisulfonyl piperazines, were designed and synthesized. These target compounds were divided into two series, namely 4-methoxy-1,3-benzenedisulfonyl piperazines of series 1 and 4-ethoxy-1,3-benzenedisulfonyl piperazines of series 2. With adenosine diphosphate (ADP), arachidonic acid (AA) and collagen as inducers, respectively, the Born turbidimetric method was used to screen the antiplatelet activity in vitro of all target compounds at a concentration of 1.
View Article and Find Full Text PDFZhongguo Ying Yong Sheng Li Xue Za Zhi
July 2021
To investigate the role of cell autophagy in lung ischemia/reperfusion injury in rats. Forty SD rats were randomly divided into 5 groups (=8): ①Sham operated group (sham group):just open rat chest for 3.5 h; ②Ischemia/reperfusion group (I/R group):after open chest, clamp pulmonary hilus for 0.
View Article and Find Full Text PDFBackground: A Chinese folk medicine plant Pleurospermum lindleyanum possesses pharmacological activities of heat-clearing, detoxifying and preventing from hepatopathy, coronary heart disease, hypertension, and high altitude sickness. We isolated and characterized its constituents to investigate its synergistic effects against human hepatoma SMMC-7721 cells.
Objective: The aim of this study was to explore the synergistic anti-cancer activities of isolates from P.
Human retinal pigment epithelium cells under hydrogen peroxide-induced oxidative stress and a ligustrazine-based protective effect were investigated using laser tweezers Raman spectroscopy. Protein and lipid were significantly affected by oxidative damage, along with increased reactive oxygen species (ROS) level within cells. The effects of ligustrazine against the reaction of ROS with protein seemed to be able to inhibit such damages but were limited during the desamidization of amides, along with additional effect on nucleic acid base and DNA phosphoric acid skeleton.
View Article and Find Full Text PDFSix new C-21 steroidal glycosides (1-6) were separated from the root of Dregea sinensis Hemsl. and their structures were elucidated using extensive nuclear magnetic resonance, mass spectrometry, and infrared spectral analyses. Isolated compounds were evaluated for antitumor activity, which showed that compound 3 had moderate activity in Jurkat cells (IC 19.
View Article and Find Full Text PDFCardiovasc Hematol Agents Med Chem
September 2015
A new class of 4-ethoxyisophthalamides is reported, based on the novel approach of linking the 4-ethoxy to Picotamide. Picotamide, as a combined inhibitor of Thromboxane A2 synthase and receptor, is synthesized in 1985 and attracted the attention of researchers. To improve our knowledge of the structure-activity relationship (SAR) and to obtain new anti-platelet drugs, total 24 unreported compounds of 4-ethoxyisophthalamides were designed and synthesized and were devised taking example by structural features of Picotamide and 4-methoxy-N1,N3-diphenylisophthalamide.
View Article and Find Full Text PDFPirt is a transmembrane protein predominantly expressed in peripheral neurons. However, the physiological and pathological roles of Pirt in hollow viscus are largely unknown. Here we show that Pirt deficiency in mice causes bladder overactivity.
View Article and Find Full Text PDFCombining the structural features of picotamide and linotroban, a series of N,N'-bis-(halogenophenyl)-4-methoxybenzene-1, 3-disulfonamides were designed and synthesized on the basic principles of drug design. The structures of target compounds were confirmed by IR, 1H NMR and HR-MS, and the in vitro antiplatelet aggregation activity was evaluated by Born turbidimetric method with adenosine diphosphate (ADP) as the platelet aggregation inducers. The assay results showed that twelve compounds (4b, 4f, 4l, 5b, 5d-5g, 5j, 5k, 5m and 5n) were found to have superior anti-platelet aggregation activities than the positive drug picotamide.
View Article and Find Full Text PDFOn the purpose of searching for the structure-activity relationship (SAR) and obtaining novel anti-platelet drugs, 41 4-methoxybenzene-1,3-isophthalamides have been described the synthesis process and in vitro activities on anti-platelet aggregation. The target compounds have been classified into four series: series 1 (ortho-substituted phenyl: 1a-1j), series 2 (meta-substituted phenyl: 2a-2k), series 3 (para-substituted phenyl: 3a-3l) and series 4 (aromatic of no substituted group and aromatic heterocyclic substituted groups: 4a-4h). The chemical structures of the target compounds were confirmed by MS, IR, (1)H NMR, and their in vitro activities on anti-platelet aggregation were tested and assessed by using Born test.
View Article and Find Full Text PDFGlyceraldehyde-3-phosphate dehydrogenase (GAPDH) is known to be a "housekeeping" protein; studies in non-cardiomyocytic cells have shown that GAPDH plays pro-apoptotic role by translocating from cytoplasm to the nucleus or to the mitochondria. However, the cardiovascular roles of GAPDH are unknown. We observed that phenylephrine (PE) (100 µM) protected against serum and glucose starvation -induced apoptosis in neonatal rat cardiac myocytes as assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and mitochondrial membrane potential depolarization.
View Article and Find Full Text PDFObjective: To observe in vivo stem cell distribution and viability after transplantation by noninvasive imaging of 18F-fluorodeoxyglucose (18F-FDG) labeled autologous mononuclear bone marrow cells.
Methods: Myocardial infarction was established in 8 swine by ligating left anterior descending coronary artery after anesthesia. Bone marrow (20 ml) was drawn through ileum.
TrkA receptor signaling is essential for nerve growth factor (NGF)-induced survival and differentiation of sensory neurons. To identify possible effectors or regulators of TrkA signaling, yeast two-hybrid screening was performed using the intracellular domain of TrkA as bait. We identified muc18-1-interacting protein 2 (Mint2) as a novel TrkA-binding protein and found that the phosphotyrosine binding domain of Mint2 interacted with TrkA in a phosphorylation- and ligand-independent fashion.
View Article and Find Full Text PDFObjective: To evaluate the impact of viable myocardium assessed by (99)Tc()m-MIBI SPECT and (18)F-fluorodeoxyglucose (FDG) PET imaging in patients with left ventricular aneurysm (LVA) underwent revascularization (RVS).
Methods: Forty-six consecutive patients with LVA (mean LVEF 36% +/- 7%), underwent (99)Tc(m)-sestamibi SPECT and (18)F-FDG PET examinations and received RVS therapy, were followed-up for a mean period of 80 +/- 27 months. Viable myocardium in aneurysm was defined as perfusion-metabolism mismatch score (MMS) >/= 2.
Unlabelled: The prognostic value of myocardial viability assessment on left ventricular (LV) aneurysms remains undetermined. We aimed, first, to evaluate the long-term survival benefit of assessing the viability of the aneurysmal myocardium in patients with ischemic cardiomyopathy and, second, in the revascularization subgroup, to compare the short-term effects on LV function and clinical symptoms in patients treated by revascularization alone or by revascularization plus aneurysmectomy.
Methods: Seventy consecutive patients with an LV aneurysm who underwent 99mTc-sestamibi SPECT and 18F-FDG PET were followed up for a median of 6.
RET receptor signalling is essential for glial-cell-line-derived neurotrophic factor (GDNF)-induced survival and differentiation of various neurons such as mesencephalic neurons. To identify proteins that mediate RET-dependent signaling, yeast two-hybrid screening was performed with the intracellular domain of RET as bait. We identified a new interaction between RET and the adapter protein SH2-Bbeta.
View Article and Find Full Text PDFBackground And Aim: Previous studies have documented the prognostic value of normal exercise Tl myocardial perfusion imaging in patients with angiographic coronary artery disease (CAD). However, data on exercise Tc-sestamibi myocardial single photon emission computed tomography (SPECT) are scant. Accordingly, the purpose of this study was to investigate the prognostic value of normal exercise Tc-sestamibi SPECT in patients with angiographic CAD.
View Article and Find Full Text PDFSeventy-eight patients with prior myocardial infarction and left ventricular dysfunction who underwent nitrate-augmented myocardial tomography were followed for 23 +/- 14 months. Event-free survival was 100% in 34 patients with myocardial viability who underwent coronary artery bypass grafting (CABG) and 53% in those who received medical therapy (p = 0.0008).
View Article and Find Full Text PDFBackground: Scintigraphic myocardial perfusion imaging is the most widely used noninvasive modality for the detection of coronary artery disease (CAD). A technique for direct imaging of exercise-induced myocardial ischemia is highly desirable and preferable over perfusion imaging but is presently unavailable. We evaluated the feasibility and diagnostic accuracy of direct imaging of exercise-induced myocardial ischemia with fluorine-18-2-deoxyglucose (18FDG).
View Article and Find Full Text PDFZhonghua Jie He He Hu Xi Za Zhi
February 2003
Objective: To assess the change of pulmonary perfusion after thrombolytic therapy in patients with acute pulmonary embolism.
Methods: Eighty patients with acute pulmonary embolism received pulmonary radionuclide perfusion imaging before and after thrombolytic therapy. Percentage of perfusion defect scores (PPDs) was calculated by semiquantitative analysis of pulmonary perfusion imaging before thrombolytic therapy (PPDsD(0)), 1 - 5 days (PPDsD(5)), 6 - 30 days (PPDsD(30)) and 3 months after thrombolytic therapy (PPDsM(3)).