Objective The aim of this study was to explore the regulatory effects and mechanism of autophagy on epithelial-to-mesenchymal transition(EMT) in idiopathic pulmonary fibrosis(IPF). Methods The experiment was divided into two group: control group and experimental group(IPF group, autophagy induction group, autophagy inhibition group). A549 cells were cultivated by the conventional method in control group. The A549 cells of the experimental group were induced by TGF-β1(5 ng/mL). Then, no further treatment was given to IPF group. Rapamycin(10 μg/L) or 3-Methyladenine(10mmol/L) was given to autophagy induction group or autophagy inhibition group respectively. The hydroxyproline content of lung tissue was measured, and the mRNA and protein levels of α-SMA, LC3-Ⅱ or LC3-Ⅱ/LC3-Ⅰ, Beclin1, E-cadherin and Vimentin were tested by Realtime PCR and Western blot. Results At each time point, the hydroxyproline content of lung tissue and the mRNA and protein levels of α-SMA and Vimentin in the experimental group were significantly higher than those in the control group（all P<0.05）. The above detections in autophagy induction group or autophagy inhibition group were significantly lower or higher than those in the IPF group（all P<0.05）. The mRNA and protein levels of LC3-Ⅱor LC3-Ⅱ/LC3-Ⅰ, Beclin1 and E-cadherin in the experimental group were significantly lower than those in the control group（all P<0.05）. Moreover, the same detections in autophagy induction group or autophagy inhibition group were significantly higher or lower than those in the IPF group（all P<0.05）. Conclusion The autophagy and EMT played an important role in IPF. Induction of autophagy might inhibit the development of IPF by inhibiting EMT, and Inhibition of autophagy could promote the development of IPF by activating EMT.

Background: MicroRNAs (miRNAs) are key regulators during tumor initiation and progression. MicroRNA-375 (MiR-375) has been proven to play a tumor-suppressive role in various types of human malignancies; however, its biological role in clear cell renal cell carcinoma (ccRCC) remains unclear. The purpose of this study was to explore the biologic role as well as the underlying mechanism of miR-375 in ccRCC progression. Methods: Quantitative polymerase chain reaction (qPCR) was applied to test the expression of miR-375 in tissues and cell lines by t-test. Functional experiments were used to investigate the biological role of miR-375 utilizing a gain-of-function strategy. The target of miR-375 was investigated by bioinformatic analysis and further verified by luciferase reporter assay, qPCR, Western blotting, and functional experiments in vitro. Results: Our study demonstrated that miR-375 was significantly downregulated in ccRCC tissues (cancer vs. normal, 0.804 ± 0.079 vs. 1.784 ± 0.200, t = 5.531 P < 0.0001) and cell lines, and loss of miR-375 expression significantly associated with advanced Fuhrman nuclear grades (Grade III and IV vs. Grade I and II, 1.000 ± 0.099 vs. 1.731 ± 0.189, t = 3.262 P = 0.003). Functional studies demonstrated that miR-375 suppressed ccRCC cell proliferation, migration, and invasion (all P < 0.05 in both 786-O and A498 cell lines). Multiple miRNA target prediction algorithms indicated the well-studied oncogene YWHAZ as a direct target of miR-375, which was further confirmed by the luciferase reporter assay, qPCR, and Western blotting. Moreover, restoration of YWHAZ could rescue the antiproliferation effect of miR-375. Conclusions The data provide the solid evidence that miR-375 plays a tumor-suppressive role in ccRCC progression, partially through regulating YWHAZ. This study expands the antitumor profile of miR-375, and supports its role as a potential therapeutic target in ccRCC treatment.
14-3-3 Proteins ; metabolism ; Carcinoma, Renal Cell ; pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; Kidney Neoplasms ; pathology ; MicroRNAs ; physiology ; Phenotype

Ferroptosis is distinct from apoptosis,autophagy,necrosis,cornification and other cell deaths from morphological,biochemical as well as genetic aspects.Ferroptosis plays a critical role in neurological diseases and cancers.Neurological diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,stroke,periventricular leukomalacia and so on,are characterized by multiple etiologies and mechanisms,and are potentially correlated with ferroptosis.Based on the recent researches on ferroptosis and neurological diseases,this review investigates ferroptosis and its role in neurological diseases.

BackgroundThe relationship between obstructive sleep apnea (OSA) and platelet reactivity in patients undergoing percutaneous coronary intervention (PCI) has not been defined. The present prospective, single-center study explored the relationship between platelet reactivity and OSA in patients with PCI.

MethodsA total of 242 patients were finally included in the study. OSA was screened overnight by polysomnography. Platelet reactivity was assessed with a sequential platelet counting method, and the platelet maximum aggregation ratio (MAR) and average aggregation ratio were calculated. All patients were assigned per apnea-hypopnea index (AHI) to non-OSA (n = 128) and OSA (n = 114) groups. The receiver operating characteristic curve analysis was used to evaluate the accuracy of AHI for high platelet reactivity (HPR) on aspirin and clopidogrel, and multivariable logistic regression was used to determine the independent predictors of HPR on aspirin and clopidogrel.

ResultsMedian AHI was significantly higher in the OSA group than in the non-OSA group (34.5 events/h vs. 8.1 events/h, Z = -13.422, P < 0.001). Likewise, median arachidonic acid- and adenosine diphosphate-induced maximum aggregation rate (MAR) in the OSA group was significantly higher than those in the non-OSA group (21.1% vs. 17.7%, Z = -3.525, P < 0.001 and 45.8% vs. 32.2%, Z = -5.708, P < 0.001, respectively). Multivariable logistic regression showed that OSA was the only independent predictor for HPR on aspirin (odds ratio [OR]: 1.055, 95% confidence interval [CI]: 1.033-1.077, P < 0.001) and clopidogrel (OR: 1.036, 95% CI: 1.017-1.056, P < 0.001). The cutoff value of AHI for HPR on aspirin was 45.2 events/h (sensitivity 47.1% and specificity 91.3%), whereas cutoff value of AHI for HPR on clopidogrel was 21.3 events/h (sensitivity 68.3% and specificity 67.7%).

ConclusionPlatelet reactivity appeared to be higher in OSA patients with PCI despite having received a loading dose of aspirin and clopidogrel, and OSA might be an independent predictor of HPR on aspirin and clopidogrel.

Adult ; Aged ; Aged, 80 and over ; Blood Platelets ; physiology ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Percutaneous Coronary Intervention ; Prospective Studies ; Sleep Apnea, Obstructive ; physiopathology ; surgery

Objective To identify the Para-Bombay blood group on the basis of its serological characteristics .Methods ABO blood typing , H antigen detection , absorption and elution test , and saliva neutralization test were conducted for serological identification of ABO blood group .PCR-SSP was used to sequence FUT1 and FUT2 genes.Results Results of ABO genotyping of eight individuals of the Para-Bombay blood group were consistent with results of their serological blood typing.Among these cases, there were 3 cases of Amh,4 cases of Bmh,and 1 case of Abmh.The results of their FUT1 genotyping were h1h1 in 3 cases, h2h2 in 2 cases and h1h2 in 3 cases.Conclusion The differentce of agglutination intensity between Ac and Bc in reverse ABO blood typing and abnormal Oc agglutination is of greet significance for Para -Bombay blood group.

OBJECTIVETo investigate the influencing factors and pathogenesis of osteopenia in the patients with hemophilia.

METHODSTwenty-three patients with hemophilia were admitted in the hospital affiliated to North China University of Science and technology from March to August 2015, including 13 severe cases, 10 mild and moderate cases. All the patients accepted the detection of serum I collagen cross-linking N terminal peptide (NTX I), osteoprotegerin (OPG), bone alkaline phosphatase (BALP), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF) and transforming growth factor-β1 (TGF-β1), the score scale of activity ability was recorded according to the criteria published by the U.S. Center for disease prevention and control in 2002, and 21 patients received the measurement of bone mineral density. According to the World Health Organization (WHO) definition, the clinical significance of bone mineral density (BMD) was assessed by measuring the Z level.

RESULTSZ level>-2 was recorded in 10 cases, Z≤-2 was recorded in 11 cases; the levels of body mass index (BMI) and human bone alkaline phosphatase (BALP) reflecting bone formation in 11 cases (Z≤-2) were lower than there in 10 cases (Z>-2) (P<0.05); the levels of BALP (r=0.489, P<0.05), IGF (r=0.538, P<0.05) and BMI (r=0.572, P<0.01) positively correlated significantly with BMD (P<0.05); the levels of bFGF (r=0.570, P<0.01) and OPG (r=0.505, P<0.05) positively correlated with NTX I, indicating bone destruction (P<0.05); the score of activity ability of severe patients was significantly lower than that of mild and moderate cases (P<0.05), BMD levels of these 2 groups were not statistically different (P>0.05).

CONCLUSIONThe BMD level does not correlate with the clinial grouping of hemophilia, the low body mass index may be a risk factor for bone lose; the mechanism of hemophilia patient's bone lose may be related with the decrease of osteogenic activity, the IGF can prevent bone lose in hemophilia, the bFGF and OPG can promote bone metabolism of the patients with hemophilia.

Alkaline Phosphatase ; metabolism ; Biomarkers ; Bone Density ; Bone Diseases, Metabolic ; pathology ; Bone and Bones ; pathology ; Collagen Type I ; metabolism ; Fibroblast Growth Factor 2 ; metabolism ; Hemophilia A ; pathology ; Humans ; Osteogenesis ; Osteoprotegerin ; metabolism ; Peptides ; metabolism ; Somatomedins ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo investigate the effects of sorafenib on human acute promyelocytic leukemia cell NB4 and its mechanism.

METHODSThe human acute promyelocytic leukemia cell NB4 was treated with different concentrations (0, 1.5, 3, 6 and 12 µmol/L) of sorafenib, the proliferation inhibitory rate of NB4 cells was assayed by MTT, the apoptosis of NB4 was determined with flow-cytomatry after treatment; after extraction of total protein, the Western blot was performed to determine the expressions of apoptosis-relatived molecules Caspase-3, Caspase-8 and MCL-1. The mRNA expressions of Caspase-3, Caspase-8 and MCL-1 were determined by RT-PCR.

RESULTSAs compared with the control group, the proliferation of NB4 significantly decreased after treatment with different concentrations of sorafenib. The sorafenib significantly induced the apopotosis of NB4 cells in time- and dose-dependent manners. Furthermore, sorafenib treatment resulted in the obvious increase of the Caspase-3 and Caspase-8 protein and mRNA expressions, and down-regulated the MCL-1 protein and mRNA expressions in NB4 cells.

CONCLUSIONSorafenib can inhibit proliferation and induce apopotosis of human acute promyelocytic leukemia cell NB4 through the expression of Caspase-3 and Caspase-8, and down-regulation of the expression of MCL-1.

Antineoplastic Agents ; Apoptosis ; Caspase 3 ; Caspase 8 ; Cell Line, Tumor ; Down-Regulation ; Humans ; Leukemia, Promyelocytic, Acute ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; T-Lymphocytes, Helper-Inducer

This study was aimed to investigate the changes of CD34(+) and CD71(+)CD45(-) cell levels in MDS and AA patients. A total of 25 cases MDS and 43 cases of AA (18 cases SAA and 25 cases of NSAA) from January 2010 to October 2013 in the Department of Hematology, affiliated hospital of Hebei United University were enrolled in this study. The complete blood count, bone marrow smears, bone marrow biopsy, karyotype analysis and bone marrow blood cell immune genotyping (mainly the proportion of CD34(+) cells, CD71(+)CD45(-) cells in nucleated cells) were carried out for all patients; the changes of CD34(+) and CD71(+)CD45(-) cell levels in patients with MDS and AA (SAA NSAA) were compared; the differences of white blood cell count, platelet count and hemoglobin concentration in patients with count of CD71(+)CD45(-) ≥ 15% or <15% were analyzed. The results showed that the count of CD34(+) in MDS group was higher than that in AA (NSAA and SAA) group (P < 0.05). The count of CD71(+)CD45(-) cells in MDS group was higher than that in SAA (P < 0.05), there was no significant difference between NSAA group and MDS group. In MDS group with CD71(+)CD45(-) ≥ 15%, the platelet count was significantly higher than that in NSAA group (P < 0.05); and there was no statistical difference for leukocyte, platelet count and hemoglobin level between MDS and NSAA group with CD71(+)CD45(-) <15% (P > 0.05). It is concluded that the count of CD34(+) cells in MDS patients is significantly higher than that in AA and SAA patients. The count of CD71(+)CD45(-) cells in MDS group is significantly higher than that of SAA group. The platelet count in MDS patients with CD71(+)CD45(-) cells ≥ 15% is significantly higher than that of the NSAA group.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anemia, Aplastic ; pathology ; Antigens, CD ; immunology ; Antigens, CD34 ; immunology ; Blood Cell Count ; Bone Marrow ; Bone Marrow Cells ; cytology ; immunology ; Female ; Flow Cytometry ; Humans ; Leukocyte Common Antigens ; immunology ; Male ; Middle Aged ; Myelodysplastic Syndromes ; pathology ; Receptors, Transferrin ; immunology ; Young Adult

Objective To evaluate risk factors and clinical outcome of coronary artery aneurysms (CAA) developed after drug-eluting stent implantation evidenced by coronary angiographic followup.Methods This study analyzed 4500 consecutive patient with de novo coronary artery stenosis receiving drug-eluting stent (DES) implantation from January 2004 to May 2009.Seven hundred and sixty patients with angiographic follow-ups at 6-8 months and 28-48 months after the index procedure were enrolled.CAA was defined as a localized dilatation exceeding 1.5 times the diameter of the adjacent artery.The independent risk factors and major adverse cardiac events (MACE) including cardiac death,myocardial infarction,target-vessel revascularization (TVR) and in-stent thrombosis were analyzed.Results CAA was detected in 70 patients with 70 lesions (9.2％,70/760).Logistic analysis showed that lesion in an infarctrelated artery (OR: 5.9,P ＜ 0.01),lesion in the left anterior descending artery (OR: 4.5,P ＜ 0.01),lesion with chronic total occlusion (OR: 3.4,P ＜ 0.05),and lesion length ＞ 33 mm (OR: 2.9,P ＜ 0.05)were independent risk factors for CAA.Follow-up duration was (1131 ±478) days.MACE was found in 19 patients and all received TVR.There were 11 patients with myocardial infarction and 8 patients with evidence of in-stent thrombosis.Mortality was zero during follow-up.Conclusions The risk factors for the development of CAA after DES are lesions in an infarct-related artery,in the left anterior descending artery,with chronic total occlusion,and with lesion length ＞ 33 mm.MACE is not uncommon in patients with CAA and long-ferm clinical follow-up is warranted for patients with CAA.

BACKGROUNDThe gender-based differences in adverse events after drug-eluting stent (DES) implantation between Chinese women and men have not been fully studied. The present study aimed to compare the 5-year clinical outcome after DES implantation in Chinese women and men.

METHODSChinese women (n = 298) and men (n = 698) with newly diagnosed de novo coronary lesions were studied after DES implantation. The primary endpoint was the occurrence of major adverse cardiac events (MACEs) over a 5-year follow-up, including myocardial infarction (MI), cardiac death, and target vessel revascularization (TVR). Propensity score matching (PSM) was used to compare the adjusted MACE rates between sexes.

RESULTSWomen differed in body habitus and had increased fasting cholesterol. Fewer women presented with MI, and they had better cardiac function with less complex disease. The unadjusted rate of MI at 3 years (2.1%) and 5 years (5.0%) and MACE (25.2%) at 5 years in men was significantly higher than that of women (0.3%, 1.0% and 17.8%, P = 0.050, P = 0.032, and P = 0.011, respectively). After PSM, the adjusted adverse events between sexes were similar. The stent thrombosis rate rapidly increased after 2 years in men.

CONCLUSIONSThere were significant gender-based differences in baseline characteristics. Chinese men had equivalent outcomes to women after DES after adjustment by PSM. The increased rate of MI in men was attributed to an increased unadjusted rate of MACE.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; therapy ; Prospective Studies ; Treatment Outcome