Abstract: Toxoplasma gondii, an opportunistic pathogenic protozoan, is widely distributed worldwide and can cause zoonoses, which is a serious threat to human health. Nowadays, the relationship between T. gondii infection and neuropsychiatric diseases has attracted researchers' attention increasingly. T. gondii infection is related to the pathogenesis of many neuropsychiatric diseases by affecting the nervous system, such as schizophrenia, depression, Alzheimer's disease, and so on. This review will focus on the relationship between T. gondii infection and neuropsychiatric diseases and summarizes the possible mechanisms of disorders resulting from T. gondii infection． It is expected that the study on the related pathogenic mechanism of T. gondii will lead to new therapeutic directions and feasible solution for the clinical treatment of neuropsychiatric diseases caused by T. gondii infection.

OBJECTIVETo evaluate the relationship between plasma trough level of imatinib and clinical outcomes in Chinese CML patients.

METHODSPlasma trough levels in 416 CML patients who received imatinib orally in six general hospitals were assessed. The correlations of imatinib plasma trough level with baseline characteristics including age, weight and BSA, and clinical response were evaluated.

RESULTS(1) Effects of age, body weight and BSA on imatinib plasma trough levels were not to be clinically significant. (2) Median imatinib plasma trough levels was 1271 (109-4329). Imatinib plasma trough level was related to dose of imatinib administration. Plasma trough levels at imatinib of dose < 400, 400 and > 400 mg were (969 ± 585), (1341 ± 595) and (1740 ± 748) µg/L (P < 0.01), respectively. (3) There was no statistic difference in imatinib plasma trough level with complete cytogenetic response [CCyR (1337 ± 571) µg/L vs no CCyR (1354 ± 689) µg/L, P = 0.255]. (4) Imatinib plasma trough level might be important for a good clinical response in some CML patients.

CONCLUSIONThere was a large interpatient variability in imatinib plasma concentration in Chinese CML patients. No correlation of imatinib plasma trough level with CCyR was observed. However, higher doses of imatinib were shown to attain greater trough plasma concentration, suggesting that imatinib plasma trough level might be important for a good clinical response in some CML patients.

Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; Benzamides ; blood ; therapeutic use ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; blood ; drug therapy ; Male ; Middle Aged ; Piperazines ; blood ; therapeutic use ; Pyrimidines ; blood ; therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVESTo construct an eucaryotic expression plasmid carrying the BMP7 gene and express in MSCs.

METHODSThe BMP7 gene was cloned into the eucaryotic expression vector pcDNA3.1. At the same time, mesenchymal stem cells (MSCs) were isolated and cultured in vitro. The plasmid carrying the BMP7 gene was transfected into MSCs.

RESULTSPCR and digesting demonstrated that the eucaryotic expression plasmid -pcDNA-BMP7 was obtained. RT-PCR and immunohistochemical methods showed that the BMP7 gene was expressed in MSCs.

CONCLUSIONConstruction of an eucaryotic expression plasmid carrying BMP7 gene and expression in MSCs provide a sound basis for gene therapy using the BMP7 gene and the ideal seeds for tissue engineering.

Bone Morphogenetic Protein 7 ; Bone Morphogenetic Proteins ; genetics ; Genetic Therapy ; Humans ; Mesenchymal Stromal Cells ; metabolism ; Plasmids ; Polymerase Chain Reaction ; Tissue Engineering ; Transforming Growth Factor beta

BACKGROUNDSkeletal muscle has recently been recognized as an endocrine organ that can express, synthesize and secrete a variety of bioactive molecules which exert significant regulatory effects. Hydrogen sulfide (H2S) is endogenously produced in mammalian tissues and participates in a number of physiological and pathophysiological processes. We aimed to verify whether H2S could be endogenously generated and released by rat skeletal muscle, and determine the biological effects of H2S in rat skeletal muscle.

METHODSThe study was divided into two parts: detection of endogenous H2S generation and release in rat skeletal muscle and determination of antioxidative activity of skeletal muscle-derived H2S. H2S content and production in tissues were detected by sensitive sulfur electrode method. The expressions of H2S producing enzymes cystathionine β-synthase, cystathionine γ-lyase and mercaptopyruvate sulfurtransferase were detected by real-time PCR and western blotting and their tissue distributions were observed by immunohistochemical and immunofluorescent analysis. Rat skeletal muscular ischemia-reperfusion (I-R) injury model was created and evaluated by histological analysis under microscope. The malondialdehyde (MDA) contents, hydrogen peroxide levels, superoxide anion and superoxide dismutase (SOD) activities were detected using spectrophotometer.

RESULTSH2S could be endogenously generated and released by skeletal muscle of Sprague-Dawley rats (H2S content: (2.06 ± 0.43) nmol/mg; H2S production: (0.17 ± 0.06) nmol×min(-1)×mg(-1)). Gene and protein expressions of the three H2S producing enzymes were detected in skeletal muscle, as well as the liver and kidney. Endogenous H2S content and production were decreased in skeletal muscles of rats with I-R skeletal muscle injury (P < 0.05). Furthermore, H2S significantly protected rat skeletal muscle against I-R injury and resulted in decreased MDA content, reduced hydrogen peroxide and superoxide anion levels, but increased SOD activity and protein expression in skeletal muscles (all P < 0.01).

CONCLUSIONH2S generation pathway exists in rat skeletal muscle and it acts as an antioxidant in skeletal muscle.

Animals ; Blotting, Western ; Hydrogen Peroxide ; metabolism ; Hydrogen Sulfide ; metabolism ; Immunohistochemistry ; Male ; Malondialdehyde ; metabolism ; Muscle, Skeletal ; metabolism ; Oxidative Stress ; physiology ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Superoxides ; metabolism

The aim of the study was to look for the chemical constituents of the herb of Lysimachia foenum-graecum. The herb of Lysimachia foenum-graecum was extracted with 70% EtOH. The isolation and purification was performed with a combination of multi-column chromatography and the structure was determined by spectral analysis. The flavonoid compound was obtained and elucidated as kaempferol-7-O(4"-(E)-p-coumaroyl-)-alpha-L-rhmanopyranosyl)-3-O-beta-D-glucopyranosyl (1-->4)-alpha-L-rhmanopyranosyl (1-->2)-beta-D-glucopyranoside. It is a new flavonoid compound.
Flavonoids ; chemistry ; isolation & purification ; Glucosides ; chemistry ; isolation & purification ; Molecular Conformation ; Molecular Structure ; Plant Components, Aerial ; chemistry ; Plants, Medicinal ; chemistry ; Primulaceae ; chemistry

OBJECTIVETo investigate molecular mechanism of tanshinone II A inducing differentiation and apoptosis in acute promyelocytic leukemia NB4 cells.

METHODNB4 cells were cultured in vitro and treated with tanshinone II A and observed cellular morphology, cell category and the cellular proliferation. DNA microarray technique was used to analyze the gene expression profiles of NB4 cells induced by tanshinone II A.

RESULT92.8% of NB4 cells treated with 0.5 mg x L(-1) tanshinone II A were induced into mature neutrophils, in which myetocytes and melamyetocytes were 27.0%, banded and segmented neutrophits 68.2%. Cell growth were inhibited. cDNA microarray showed the enormously expressed 183 genes including 23 differentiation associated genes, and other interrelated genes.

CONCLUSIONTanshinone II A inducing differentiation in NB4 cells may be via regulation of many kinds of genes, especially differentiation associated genes expression. This partially explained the molecular mechanism of tanshinone II A inducing differentiation.

Cell Differentiation ; drug effects ; Cell Line, Tumor ; Diterpenes, Abietane ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Leukemic ; drug effects ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; genetics ; metabolism ; Phenanthrenes ; pharmacology

OBJECTIVETo compare the morphological difference between dermal tissue of normal skin and that of scar in rat, and to explore its structural pattern.

METHODSThe full-thickness skin and the scar tissue formed 3 weeks after wound healing from SD rats were harvested as samples, which were prepared appropriately afterwards. Samples were scanned and imaged with synchrotron radiation technology, micro-CT, and phase-contrast imaging technology. The images were rebuilt with three-dimensional software.

RESULTSThe micro-CT was materialized by using X-ray generated by synchrotron radiation light source. The structure of dermal tissues was clearly shown with the assistance of phase-contrast imaging technology in the process. It was demonstrated that the dermal tissues of normal skin of rat were mainly composed of collagenous fibers, which twined together to form an olive-like structure. These olive-like structures as basic units were arranged randomly in a certain way. The collagenous fibers in dermal tissue of the scar were arranged in a parallel manner, while some fibers were crooked and arranged in a disorderly manner.

CONCLUSIONSDermal tissue of normal skin in rat has stable three-dimensional structure, and its basic structure and manner of composition are obviously different from those of scar dermal tissue.

Animals ; Cicatrix ; diagnostic imaging ; Dermis ; diagnostic imaging ; pathology ; Imaging, Three-Dimensional ; methods ; Male ; Microscopy, Phase-Contrast ; Rats ; Rats, Sprague-Dawley ; Skin ; diagnostic imaging ; Synchrotrons ; Tomography, X-Ray Computed ; Wound Healing

BACKGROUNDRecently, due to the rapid development of proteomic techniques, great advance has been made in many scientific fields. We aimed to use magnetic beads (liquid chip) based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) technology to screen distinctive biomarkers for lung adenocarcinoma (adCA), and to establish the diagnostic protein profiles.

METHODSUsing weak cation exchange magnetic beads (MB-WCX) to isolate and purify low molecular weight proteins from sera of 35 lung adCA, 46 benign lung diseases (BLDs) and 44 healthy individuals. The resulting spectra gained by anchor chip-MALDI-TOF-MS were analyzed by ClinProTools and a pattern recognition genetic algorithm (GA).

RESULTSIn the working mass range of 800 - 10 000 Da, 99 distinctive peaks were resolved in lung adCA versus BLDs, while 101 peaks were resolved in lung adCA versus healthy persons. The profile gained by GA that could distinguish adCA from BLDs was comprised of 4053.88, 4209.57 and 3883.33 Da with sensitivity of 80%, specificity of 93%, while that could separate adCA from healthy control was comprised of 2951.83 Da and 4209.73 Da with sensitivity of 94%, specificity of 95%. The sensitivity provided by carcinoembryonic antigen (CEA) in this experiment was significantly lower than our discriminatory profiles (P < 0.005). We further identified a eukaryotic peptide chain release factor GTP-binding subunit (eRF3b) (4209 Da) and a complement C3f (1865 Da) that may serve as candidate biomarkers for lung adCA.

CONCLUSIONMagnetic beads based MALDI-TOF-MS technology can rapidly and effectively screen distinctive proteins/polypeptides from sera of lung adCA patients and controls, which has potential value for establishing a new diagnostic method for lung adCA.

Adenocarcinoma ; blood ; diagnosis ; Adult ; Aged ; Female ; Humans ; Lung Neoplasms ; blood ; diagnosis ; Magnetics ; Male ; Microspheres ; Middle Aged ; Sensitivity and Specificity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods

The purpose of this study was to investigate the effects of Celecoxib on the proliferation of the FLT3-ITD positive and negative acute myeloid leukemia cells and its mechanism. The proliferation inhibition effect of Celecoxib with different doses on the FLT3-ITD positive cells MV4-11 and the FLT3-ITD negative K562 cells was detected by CCK-8 method, the cell apoptosis was determined by flow cytometry, and the MEK, Mcl-1, pAKT expression was tested by Western blot. The results showed that Celecoxib inhibited the proliferation of both MV4-11 and K562 cells, but the IC50 for MV4-11 was (29.14 ± 2.4) µmol/L, which was significantly lower than that of K562 cells (39.84 ± 1.0) µmol/L (P < 0.05); The induced apoptosis rate of Celecoxib at 20-80 µmol/L on MV4-11 was not observed, but there was apparent influence on K562 at the same concentration. Western blot showed that Celecoxib down-regulated the expression of MEK and Mcl-1 but did not change the expression of pAKT obviously on MV4-11 cells, while the expression of Mcl-1 was reduced a little, but no obvious change were found in the expression of MEK and pAKT on K562 cells. It is concluded that the Celecoxib can inhibit the proliferation of FLT3-ITD positive AML cells distinctly, and the potential mechanism may be related to the inhibition of the MEK/Mcl-1 signaling pathway.
Apoptosis ; drug effects ; Celecoxib ; Cell Proliferation ; drug effects ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Gene Expression Regulation, Leukemic ; Humans ; K562 Cells ; Leukemia, Myeloid, Acute ; drug therapy ; metabolism ; pathology ; MAP Kinase Kinase 1 ; genetics ; Myeloid Cell Leukemia Sequence 1 Protein ; genetics ; Proto-Oncogene Proteins c-akt ; genetics ; Pyrazoles ; pharmacology ; Signal Transduction ; Sulfonamides ; pharmacology ; fms-Like Tyrosine Kinase 3 ; genetics

BACKGROUNDMyocardial tissue-level perfusion failure is associated with adverse outcomes following ST-elevation myocardial infarction (STEMI) despite successful epicardial recanalization. We have developed a new quantitative index-thrombolysis in myocardial infarction (TIMI) myocardial perfusion frame count (TMPFC)--for assessing myocardial tissue level perfusion. However, factors affecting this novel index of myocardial perfusion are currently unknown.

METHODSA total of 255 consecutive STEMI patients undergoing primary angioplasty were enrolled. Myocardial tissue level perfusion was assessed by TMPFC, which measures the filling and clearance of contrast in the myocardium using cine-angiographic frame counting. We differentiate three groups with two cut off values for TMPFC: a TMPFC of 90 frames was the upper boundary of the 95% confidence interval (CI) for the TMPFC observed in normal arteries, and a TMPFC of 130 was the 75th percentile of TMPFC.

RESULTSSTEMI patients with TMPFC > 130 frames (68 patients, 26.7%) had higher clinical and angiographic risk factor profiles as well as a higher 30-day MACE rate compared with those with TMPFC ≤ 90 frames and those with TMPFC > 90 and ≤ 130 frames. Multivariable analysis identified that the independent predictors of TMPFC > 130 frames were age ≥ 75 years (OR 2.08, 95%CI 1.21 to 3.58, P = 0.007), diabetes (OR 1.37, 95%CI 1.01 to 1.86, P = 0.042), Killip class ≥ 2 (OR 1.52, 95%CI 1.05 to 2.21, P = 0.027), and prolonged pain-to-balloon time (OR 1.73, 95%CI 1.07 to 2.79, P = 0.013). TMPFC > 130 frames was identified as the strongest independent predictor of 30-day major adverse cardiac event (MACE) (OR 2.77, 95%CI 1.21 to 6.31, P = 0.008), along with age ≥ 75 years (OR 2.19, 95%CI 1.11 to 4.33, P = 0.016), female gender (OR 1.67, 95%CI 1.03 to 2.70, P = 0.038), and Killip class ≥ 2 (OR 1.83, 95%CI 1.07 to 3.14, P = 0.021).

CONCLUSIONSSTEMI patients with poor myocardial perfusion assessed by TMPFC had higher risk factor profiles. Advanced age, diabetes, higher Killip class, and longer ischemia time were independent predictors of impaired TMPFC after primary percutaneous coronary intervention. These results emphasize that particular attention should be paid on myocardial microvascular reperfusion in STEMI patients with these risk factors.

Aged ; Angioplasty, Balloon, Coronary ; Coronary Angiography ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; diagnostic imaging ; pathology ; therapy ; Myocardial Reperfusion ; Myocardium ; metabolism ; pathology