Antimony ; urine ; Flow Injection Analysis ; Spectrometry, Fluorescence ; methods ; Spectrophotometry, Atomic ; methods

OBJECTIVETo investigate the role of p38 MAPK on ischemic postconditioning (IPO) attenuating pneumocyte apoptosis after lung ischemia/reperfusion injury (LIRI).

METHODSForty adult male SD rats were randomly divided into 5 groups based upon the intervention (n = 8): control group (C), LIR group (I/R), LIR + IPO group (IPO), IPO + solution control group (D), IPO + SB203580 group (SB). Left lung tissue was isolated after the 2 hours of reperfusion, the ratio of wet lung weight to dry lung weight (W/D), and total lung water content (TLW) were measured. The histological structure of the left lung was observed under light and electron transmission microscopes, and scored by alveolar damage index of quantitative assessment (IQA). Apoptosis index (AI) of lung tissue was determined by terminal deoxynuleotidyl transferase mediated dUTP nick end and labeling (TUNEL) method. The mRNA expression and protein levels of and Bax were measured by RT-PCR and quantitative immunohistochemistry (IHC).

RESULTSCompared with C group, W/D, TLW, IQA, AI and the expression of Bax of I/R were significantly increased, the expression of Bcl-2 and Bcl-2/Bax were significantly decreased (P < 0.05, P < 0.01), and was obviously morphological abnormality in lung tissue. Compared with I/R group, all the indexes of IPO except for the expression of Bcl-2 and Bcl-2/ Bax were obviously reduced, the expression of Bcl-2 and Bcl-2/Bax were increased (P < 0.05, P < 0.01). All the indexes between D and IPO were little or not significant( P > 0.05). The expression of Bcl-2 and Bcl-2/Bax of SB were significantly increased and other indexes were reduced than those of IPO (P < 0.05, P < 0.01).

CONCLUSIONIPO may attenuate pneumocyte apoptosis in LIRI by inactivation of p38 MAPK, up-regulating expression of Bcl-2/Bax ratio.

Alveolar Epithelial Cells ; cytology ; Animals ; Apoptosis ; Disease Models, Animal ; Ischemic Postconditioning ; Lung ; blood supply ; enzymology ; pathology ; Male ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; enzymology ; pathology ; prevention & control ; bcl-2-Associated X Protein ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo investigate the effects of paraquat on microRNA expressions in PCl2 cells, and to explore the regulatory mechanism of bcl-2.

METHODSWe used PC12 cells as a popular in vitro cell model system for characterizing the dopaminergic neuron. After 24 h treatment with different concentrations of PQ (0, 62.5 ümol/L), expression difference of microRNA was detected by microarray and examined by real-time quantitative PCR (RT-PCR). Cell apoptosis was analyzed with flow cytometry (FCM) and the relative levels of miR-34a, miR-Let-7e were measured by RT-RCR following the PCl2 cells treatment with 0, 62.5, 125, 250, 500, 1000 ümol/L PQ. Meanwhile, the protein expression of bcl-2 was evaluated by western blot according to forecasting targets analysis databases.

RESULTSCell viability decreased and cell apoptosis increased with increasing PQ concentrations (from 125 to 1000 ümol/L) in a dose-dependent manner (P < 0.05 or P < 0.01). MiRNA microarray showed that after 62.5 ümol/L PQ treatment, 11 miRNAs were significantly up-regulated while 8 miRNAs were down-regulated compared with control (P < 0.01). We chose miR-34a, miR-Let-7e which appeared most remarkable changes in microarray to examine by RT-PCR. It revealed that the level of miR-34a gradually ascended while miR-Let-7e declined after PQ treatment, which are accordant to the microarray results. The protein expression of bcl-2 treated with PQ significantly decreased compared with control and presented a negative correlation with the expression of miR-34a (P < 0.05 or P < 0.01).

CONCLUSIONThe alteration of miRNAs expression may be involved in the neurotoxicity of PQ. Especially, mir-34a negatively regulated the level of bcl-2, and thus plays a key role in PQ-induced cell apoptosis.

Animals ; Apoptosis ; drug effects ; MicroRNAs ; genetics ; PC12 Cells ; Paraquat ; toxicity ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats

AIM To observe the effects of Tangzhi Kangping Granules (Astragali Radix,Ligustri lucidi Fructus,Schisandrae chinensis Fructus,etc.) on regulating blood sugar and lipid of rats with glucose and lipid metabolism disorders.METHODS Among the seventy rats for the trial,ten rats were randomly assigned to normal control group,the other 60 rats were injected with STZ citric acid-sodium citrate solution (60 mg/kg) combined with high-fat emulsion (10 mL/kg) for 4 weeks to be the models of glucose and lipid metabolism disorders.The model rats were divided into model control group,mefformin + fenofibrate group,Xiaoke Pills + Xuezhikang group,and high,medium and low dose Tangzhi Kangping Granules groups.After 4-week intragastric administration,the rats had their levels of fasting serum glucose (GLU),triglyceride (TG),total cholesterol (TC),high density lipoprotein cholesterol (HDL-C),low density lipids (LDL-C),insulin (INS),adiponectin (ADP),leptin (Leptin),interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) measured.RESULTS Compared with the model control group,the rats in high,medium and low dose Tangzhi Kangping Granules groups displayed significantly decreased serum contents of GLU,TG and TC,lowered levels of LDL-C,ADP,Leptin,IL-6,TNF-α,and yet significantly increased levels of HDL-C and INS.CONCLUSION Tangzhi Kangping Granules,a blood sugar andlipid regulator may adjust the levels of insulin,adiponectin and leptin,and therefore improves the body's inflammatory environment to alleviate insulin resistance.

OBJECTIVEWe propose an image-based key frames gating method for intravascular ultrasound (IVUS) sequence based on manifold learning to reduce motion artifacts in IVUS longitudinal cuts.

METHODSWe achieved the gating with Laplacian eigenmaps, a manifold learning technique, to determine the low-dimensional manifold embedded in the high-dimensional image space. A distance function was constructed by the low-dimensional feature vectors to reflect the heart movement. The IVUS images were classified as end-diastolic and non-end-diastolic based on the distance function, and the IVUS images collected in end-diastolic stage constitutes the key frames gating sequences.

RESULTSWe tested the algorithm on 13 in vivo clinical IVUS sequences (images 915±142 frames, coronary segments length 15.24±2.37 mm) to calculate the vessel volume, lumen volume, and the mean plaque burden of the original and gated sequences. Statistical results showed that both the vessel volume and lumen volume measured from the gated sequences were significantly smaller than the original ones, indicating that the gated sequences were more stable; the mean plaque burden was comparable between the original and gated sequences to meet the need in clinical diagnosis and treatment. In the longitudinal views, the gated sequences had less saw tooth shape than the original ones with a similar trend and a good continuity. We also compared our method with an existing gating method.

CONCLUSIONThe proposed algorithm is simple and robust, and the gating sequences can effectively reduce motion artifacts in IVUS longitudinal cuts.

Algorithms ; Angiography ; methods ; Artifacts ; Electrocardiography ; Humans ; Motion ; Reproducibility of Results ; Sensitivity and Specificity

OBJECTIVETo investigate the effect of angiotension II (AngII) on the activation of NLRP3 inflammasome and the expression of interleukin-1β (IL-1β) in human umbilical vein endothelial cells (HUVECs).

METHODSHUVECs cultured in vitro were treated with different concentrations of AngII for varying lengths of time to determine the optimal concentration and time for AngII exposure. To test the impact of different agents on the effect of AngII exposure, HUVECs were pretreated with AngII receptor blocker losartan, NAD(P)H inhibitor DPI and H(2)O(2) scavenger CAT, caspase 1 inhibitor YVAD, or NLRP3 siRNA for silencing NLRP3, and the protein levels of NOX4, NLRP3, caspase-1 and IL-1β in HUVECs were analyzed by Western blotting.

RESULTSAngII treatment at the optimal concentration (10(-9) mol/L) for 12 h significantly increased the protein levels of NOX4, NLRP3, caspase1 and IL-1β in HUVECs. Pretreatment with losartan, DPI, CAT, YVAD, or NLRP3 siRNA all attenuated the effects of AngII on the cells.

CONCLUSIONAngII can induce vascular inflammation by promoting the production of reactive oxygen species and activating NLRP3 inflammasome to increase the protein expression of IL-1β in HUVECs.

Adaptor Proteins, Signal Transducing ; pharmacology ; Angiotensin II ; pharmacology ; Blotting, Western ; Carrier Proteins ; metabolism ; Caspase 1 ; metabolism ; Human Umbilical Vein Endothelial Cells ; metabolism ; Humans ; Hydrogen Peroxide ; Inflammasomes ; metabolism ; Interleukin-1beta ; metabolism ; NADPH Oxidase 4 ; NADPH Oxidases ; metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein ; RNA, Small Interfering ; Reactive Oxygen Species ; metabolism

Colorectal cancer is a common malignant tumor in gastrointestinal tract. Its onset and development are associated with its own characteristics as well as the tumor microenvironment (TME) in which tumor-associated macrophages (TAMs) are the most abundant immune cells. After being recruited to the tumor site and stimulated by different signals in TME, TAMs can grow into two different subtypes, namely M1 and M2. TAMs are mainly manifested as M1 macrophages in the early stage of colorectal cancer, mediating the immune response to inhibit tumor growth. In the late stage, TAMs mainly grow into M2 macrophages, showing the ability to suppress immunity, stimulate the proliferation of tumor cells and tumor angiogenesis, and promote the invasion and metastasis of tumor cells. It has been found that intervention in TAMs polarization can regulate its relationship with the onset and development of colorectal cancer.
Humans ; Tumor-Associated Macrophages ; Macrophages ; Tumor Microenvironment ; Colorectal Neoplasms

OBJECTIVETo investigate whether serum ferritin (SF) level may be used as a indicator for predicting mortality of patients with myelodysplastic syndrome (MDS).

METHODSA total of 151 patients with MDS were followed up in our study, their blood routine indicators, bone marrow blasts and SF level were detected. All of the patients were divided into the dead group and survival group.

RESULTSThe average survival time of all patients was 30.0 ± 10.86 months. There were statistical differences in age, IPSS score, chromosome grouping and SF level between 2 groups (P < 0.05). COX model analysis showed that age, MDS type, IPSS score, chromosome grouping and SF level all were related with mortality of patients with MDS, which were risk factors of death for patients with MDS (P < 0.05). The receiver-operating characteristic curve (ROC) area for SF was 0.826 with a Cut off value of 622.95, the sensitivity and specificity was 77.5% and 75% respectively. Log-rank test showed that the mortalities of patients with different levels of SF were statistically and very significantly different (P < 0.01).

CONCLUSIONThe age, IPSS score, chromosome grouping and SF level closely correct with mortality of the patients with MDS, the SF level may be considered as a predictor of death for MDS patients.

Ferritins ; blood ; Humans ; Myelodysplastic Syndromes ; blood ; diagnosis ; Prognosis ; Risk Factors

OBJECTIVETo investigate the diagnostic value of circulating serum miRNA for multiple myeloma.

METHODSForty blood samples from patients with multiple myeloma were collected from July 2013 to June 2014 in Department of Hematology, Zhongshan Hospital Affiliated to Xiamen University. The real-time quantitative PCR was performed to detect the serum expression levels of miRNAs (miR-29a, miR-155, miR-16 and miR-92a) circulating in the different stages of patients with multiple myeloma and evaluate the diagnostic value for patients with multiple myeloma.

RESULTSThe serum level of miR-29a significantly increased in newly diagnosed patients as compared to healthy donor (P<0.01), serum miR-155 levels were significantly lower as compared with healthy donor(P<0.001); The ratio of miR-29a and miR-155 was an effective biomarker for distinguishing multiple myeloma from healthy donor, their sensitivity and specificity were 80.8% and 83.3% respectively for myeloma diagnosis. the change of miR-29a expression was consistent with the changes of bone marrow plasma cells and M protein levels.

CONCLUSIONThese circulating serum microRNA, such as miR-29a, miR-155 and miR-16, may serve as potential diagnostic biomarkers for multiple myeloma, and the ratio of miR-29a/miR-155 may serve as a most useful biomarker for myeloma diagnosis.

The acute myeloid leukemia is a very common malignant tumor of hematopoietic system, which is seriously harmful to human health. The long-term survival rate of routine chemotherapy is not satisfactory, especially in the high risk patients. Resistance to chemotherapy drugs is one of the major reasons, which causes the refractorines and relapse of the acute myeloid leukemia. The microRNA found in eukaryote is an endogenous non-coding micromolecular signle-stranded RNA of 19 to 25 nt. The miRNA can degrade the specific RNA or inhibit its translation through combining to 3' untranslated regions of the specific RNA, which contributes to regulate the expression of the target gene. There are already some evidences showing that the disorder of miRNA plays an important role in the genesis and progress of the tumors. Recently, more and more researches suggest that the miRNA is also important in the genesis of drug resistance to tumors. This review summarizes the research progress and the major mechanism of drug-resistance mediated by the miRNA in AML, including multiple drug resistance, cell cycle and the tolerance to apoptosis, all of which are associated with ABC transport protein.