Search

Introduction: The characteristics of Allergic Bronchopulmonary Aspergillosis (ABPA) based on its radiological classification is still unclear., Objectives: To investigate the clinical significances of ABPA patients with central bronchiectasis (ABPA-CB) by different radiological classifications of mucus plugs., Methods: ABPA-CB patients from a pulmonary hospital between 2008 and 2015 were retrospectively included and analysed. According to the chest imaging in their first visit to physician, the ABPA-CB patients were divided into two groups based on the presence of high-attenuation mucus (HAM) or low-attenuation mucus (LAM). The primary endpoint was ABPA relapse within 1 year since the glucocorticoid withdrawal. The relationship between the imaging findings and the clinical prognosis was illuminated., Results: A total of 125 ABPA patients were analysed in this study. Compared to the LAM group, the HAM group presented higher blood eosinophil cells counts, higher rates of Aspergillus detection isolated in sputum and expectoration of brownish-black mucus plugs, more affected lobes and segments, poorer pulmonary function and higher rate of relapse., Conclusions: The clinical characteristics and prognosis of ABPA-CB patients are closely related to its radiological phenotype of mucus plugs in the central bronchiectasis. Clinicians should promote a diversity of personalized treatments for different patients with different radiological characteristics., (© 2019 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Objective: To compare the gene mutational spectrum between elderly and young adults with acute myeloid leukemia(AML) based on next generation sequencing(NGS)., Methods: The specimens of 250 AML patients in first affiliated hospital of Zhengzhou University from January 2018 to November 2018 were collected and analyzed retrospectively. The mutation of 22 related genes were detected by using AML NGS chips. Then, the differences between elderly (≥60 years old) and young adults (＜60 years old) were compared., Results: The most frequent mutations of 250 patients were as follows: NPM1(22.4%), FLT3-ITD(18.8%), NRAS(17.2%), DNMT3A(14.4%), TET2(11.6%), IDH2(9.6%), Biallelic CEBPA(8.8%), Moallelic CEBPA(8.4%), KIT(8.4%), RUNX1(7.6%), IDH1(7.6%), ASXL1(6.0%), U2AF1(5.2%), SRSF2 (3.2%), SF3B1(3.2%), TP53(2.4%), KRAS(2.0%). The NPM1, CEBPA, DNMT3A mutation significantly increased in intermediate prognosis group while KIT significantly increased in favourable prognosis group. The TET2 and IDH2 mutation rate in elderly patients were significantly higher than that in young patients (21.8% vs 8.7%) (χ 2 =7.180, P=0.007) and (20.0% vs 6.7%) ( χ 2 =8.788, P=0.003) respectively. Compared with young patients, the frequencies of DNA methylation and demethylation mutations (including DNMT3A, TET2, IDH1, IDH2) and RNA splicing enzyme mutations (inc-luding SRSF2, SF3B1, U2AF1, ZRSR2) in elderly patients significantly increased(67.3% vs 36.4%) (χ 2 =16.653, P=0.000) and (23.6% vs 8.7%)(χ 2 =9.041, P=0.003) respectively., Conclusion: The gene mutational spectrum in elderly and young adult AML shows heterogeneity. Compared with young adults, the frequencies of DNA methylation and demethylation mutations and RNA splicing enzyme mutations in elderly patients significantly increase.

Background: To investigate the relationship between serum lipid levels and disease progression during chronic hepatitis B virus infection., Methods: We selected 73 healthy controls and 163 patients with chronic HBV infection as the study subjects. The chronic HBV infection patients were divided into the HBV carrier group (74 patients), chronic hepatitis B group (71 patients), and liver cirrhosis group (21 patients). The age, gender, body mass index, blood lipid index, liver function index, and HBV DNA levels of all participants were tested and recorded. A t-test or the Mann-Whitney U test was used to compare the data between two groups; data from multiple groups were compared using one-way ANOVA or the Kruskal-Wallis Test., Results: We observed that the serum HDL cholesterol (1.00 ± 0.30 mmol/L in the HBV-infected group, 1.29 ± 0.23 mmol/L in the control group) and APOA (1.29 ± 0.35 mmol/L, 1.36 ± 0.21 mmol/L, respectively) concentrations were significantly lower in the HBV-infected group than in the control group (p < 0.05). As the disease progressed, the blood lipid and lipoprotein values were significantly lower in the cirrhosis group TC (3.26 ± 1.00 mmol/L), HDL cholesterol (0.77 ± 0.33 mmol/L), LDL cholesterol (2.09 ± 0.62 mmol/L), and APOB (0.57 ± 0.18 mmol/L) compared with the control group, the carrier group, and the chronic hepatitis B group (p < 0.05). The serum HBV DNA level was significantly, positively correlated with the blood HDL concentration (carrier group R = 0.340, p = 0.02; chronic hepatitis B group R = 0.329, p = 0.014). There was no correlation between the HBV DNA and lipid levels in patients with cirrhosis., Conclusions: Serum lipid metabolic derangement was associated with disease progression during chronic HBV infection. Liver function and blood lipid levels were significantly lower in patients with hepatitis B-related cirrhosis.

Objective: To investigate the effect of metformin on the proliferation, apoptosis and energy metabolism of acute myeloid leukemia (AML) K562 cells and the possible mechanism., Methods: Different doses (0, 5, 10, 20 and 30 mmol/L) of metformin was added into the K562 cells, which were cultivated for 24 h, 48 h and 72 h. The inverted optical microscope was used to observe the cell growth, CCK 8 was used to detect the cell vitality. The appropriate metformin doses (0, 10, 20 and 30 mmol/L) and the best time (48 h) were selected for subsequent experiments. The flow cytometer with Annexin V-FITC /PI doulde staining was used to detect apoptosis; the glucose detection kit and lactate detection kit were used to detect glucose consumption and lactate production; fluorescence quantitative PCR was used to detect glycolysis-related gene expression, and Western blot was used to detect protein expression., Results: Metformin inhibited the proliferation of K562 cells in a dose-dependent manner (r=0.92), and the relative survival in the 30 mmol/L group was as low as 19.84% at 72 h. When treated with metformin for 48 h, the apoptosis rates of 0, 10, 20 and 30 mmol/L groups were 5.14%, 12.19%, 26.29% and 35.5%, respectively. Compared with the control group, the glucose consumption and lactate secretion of K562 cells treated with metformin were significantly reduced (P<0.05), and showed a dose-dependent effect(r=0.94,r=0.93,respectively). Metformin inhibited the expression of GLUT1, LDHA, ALDOA, PDK1, and PGK1 genes of K562 cells (P<0.05) showing a dose-dependent manner(r=0.83，r=0.80，r=0.72，r=0.76，r=0.73,respectively). Metformin inhibited the expression of P-Akt, P-S6, GLUT1, LDHA proteins of K562 cells(P<0.05), showing a dose-dependent relationship(r=0.80，r=0.92，r=0.83，r=0.92,respectively)., Conclusion: Metformin can inhibit the growth and proliferation of K562 cells and promote the apoptosis of K562 cells by inhibiting glycolysis energy metabolism. PI3K/Akt/mTOR signaling pathway may be one of the molecular mechanisms of metformin on k562 cells.

Objective: To explore the reversal effect of pioglitazone (PIO) on multidrug resistance in K562/ADR cells and its mechanism., Methods: The proliferation inhibition rate, half inhibition concentration (IC 50 ) and drug-resistance reversal multipe were detected and the curve of proliferation inhibition rate was drawn by MTT assay, the transcription of PPARγ, CYP2C8 and CYP2J2 genes was detected by RT-PCR; the expression of PPARγ, CYP2C8 and CYP2J2 proteins was detected by Western blot., Results: The IC 50 of PIO on K562 and K562/ADR cells for 60 h was 326.7 μmol/L and 349.1 μmol/L respectively. The reversal multiple of 30 μmol/L PIO on ADR-resistance of K562/ADR cells was 6.4. After treatment of K562/ADR cells with PIO, the transcription of CYP2C8 and CYP2J2 and the protein expression of CYP2C8 and CYP2J2 significantly decreased, the transcription of PPARγ gene and the expression of PPARγ protein were not changed., Conclusions: Pioglitazone can reverse the adriamycin-resistance in K562/ADR cells that is closely related to the decrease of protein expression of CYP2C8 and CYP2J2. Pioglitazone is an effective multidrug resistance reversal agent for tumors.

Objective: To explore the changes of autophagic activity after resistance of U266 cells to bortezomib (Bor) and its mechanisms., Methods: The proliferation inhibition rate, 50% inhibitory concentration (IC 50 ), drug-resistance coefficient, drug-resistance reversed multiple by 3-methyladenine (3-MA) in U266 and U266/Bor cells treated with Bor were detected and calculated by using MTT method, then the proliferation inhibition curve was drawed. The Western blot was used to detect the expression of LC3-I, IC3-II, p-mTOR, Beclin-1, ATG5 and ATG7 proteins., Results: The Bor showed the its proliferation inhibition effect on U266 cells and U266/Bor cells, IC 50 of Bor on U266 and U266/Bor cells on 24 hours were 35.7 nmol/L and 526.5 nmol/L respectively; the drug-resistance coefficient was 14.7; the drug-resistance reversed multiple by 3-MA was 2.7. The expression of LC3-II, Beclin11, ATG5 and ATG7 in U266/Bor cells was higher than that in U266 cells; after the treatment with Bor for 24 h, the expression levels of LC3-II, Beclin-1, ATG5 and ATG7 in U266 cells all decreased, as compared with levels before treatment; while the expression levels of LC3-II, Beclin-1, ATG5 and ATG7 in U266/Bor cells were higher than those before treatment. There were no significant difference of p-mTOR expression among U266, U266+Bor, U266/Bor, U266/Bor+Bor cells., Conclusion: The increase of autophagy closely relates with resistance of U266 cells to bortezomib, moreover with up-regulation of Beclin-1, ATG5 and ATG7 expression.

Cypripedium tibeticum is a threatened orchid which efficient conservation requires knowledge of its extent and structure of genetic variation. Using two chloroplast DNA fragments ( rps 16 and trn L-F), we analyzed 157 individuals from 9 populations representing the species range in China. Seven haplotypes were identified. C. tibeticum had high total genetic diversity ( H T  = 0.80) with major contribution to this diversity made by among-population component ( G ST  = 0.64, Φ ST  = 0.86). However, despite high population differentiation there was no clear phylogeographic structure. The populations CY and DC made the greatest contribution to the total gene diversity as well as allelic richness. The possible mechanisms and implications of these findings for conservation of the species are discussed.

Objective: This study aimed to evaluate the clinical effect of pulp-less molars with defects of different degrees repaired by cast ceramic onlays of three marginal types., Methods: A total of 165 endodontically treated molars of 105 patients were included in this study and were divided into three kinds of defect (mild, moderate, severe) according to the number of remaining axial walls. Each defect was divided into three groups according to the shape of edge to edge, bevel edge, and concave shoulder. After tooth preparation, the casting of ceramic onlays was performed. Treatment follow-up was done for the evaluation of the success and survival rates of three groups under the same defect., Results: The average follow-up was 925.44 days. Under the mild defect, the success and survival rates of the edge to edge onlays were respectively 100% and 100%; bevel edge onlays, 100% and 100%; and concave shoulder onlays, 94.4% and 100%. Under the moderate defect, the success and survival rates of the edge to edge onlays were respectively 96.0% and 100%; bevel edge onlays, 80.0% and 93.3%; and concave shoulder onlays, 95.2% and 95.2%. Under the severe defect, the success and survival rates of the edge to edge onlays were respectively 95.2% and 100%; bevel edge onlays, 73.7% and 89.5%; and concave shoulder onlays, 73.3% and 80.0%. Under different defects, the success or survival rates of the three kinds of onlays had no significant difference (P>0.05)., Conclusions: The edge to edge type is the most preferable way of onlay tooth preparation and can achieve good clinical results in the mild, middle, and severe tooth defection with root canal treatment.

Nucleoside diphosphate kinase 1 (NME1) is well-known as a tumor suppressor that regulates p53 function to prevent cancer metastasis and progression. However, the role of NME1 in virus-infected cells remains unknown. Here, we showed that NME1 suppresses viral replication in foot-and-mouth disease virus (FMDV)-infected cells. NME1-enhanced p53-mediated transcriptional activity and induction of interferon-inducible antiviral genes expression. FMDV infection decreased NME1 protein expression. The 2B and VP4 proteins were identified as the viral factors that induced reduction of NME1. FMDV 2B protein has a suppressive effect on host protein expression. We measured, for the first time, VP4-induced lysosomal degradation of host protein; VP4-induced degradation of NME1 through the macroautophagy pathway, and impaired p53-mediated signaling. p53 plays significant roles in antiviral innate immunity by inducing several interferon-inducible antiviral genes expression, such as, ISG20, IRF9, RIG-I, and ISG15. VP4 promoted interaction of p53 with murine double minute 2 (MDM2) through downregulation of NME1 resulting in destabilization of p53. Therefore, 5-flurouracil-induced upregulation of ISG20, IRF9, RIG-I, and ISG15 were suppressed by VP4. VP4-induced reduction of NME1 was not related to the well-characterized blocking effect of FMDV on cellular translation, and no direct interaction was detected between NME1 and VP4. The 15-30 and 75-85 regions of VP4 were determined to be crucial for VP4-induced reduction of NME1. Deletion of these VP4 regions also inhibited the suppressive effect of VP4 on NME1-enhanced p53 signaling. In conclusion, these data suggest an antiviral role of NME1 by regulation of p53-mediated antiviral innate immunity in virus-infected cells, and reveal an antagonistic mechanism of FMDV that is mediated by VP4 to block host innate immune antiviral response.

Background: Patients with community acquired pneumonia (CAP) caused by viruses can develop severe complications, which result in hospitalization and death. The purpose of this study was to analyse the aetiology, incidence, clinical characteristics, and outcomes of CAP patients with fever during non-pandemics, and then to provide theoretical basis for accurate diagnosis and treatment in CAP patients., Methods: An enrolment system was established for monitoring the CAP patients with fever. Multiplex polymerase chain reaction (mPCR) kits were used to detect 10 viruses [influenza A and B, adenovirus (ADV), respiratory syncytial virus (RSV) A and B, picornavirus, parainfluenza virus (PIV), coronavirus, human metapneumovirus (HMPV), and bocavirus]. Data on age, gender, underlying diseases, complications, laboratory indexes, and outcomes were collected by physicians., Results: This prospective study included 320 patients with fever. Among them, 23.4% were viral-positive by mPCR, with influenza virus most prominent followed by picornavirus. Strong variation in seasonal distribution was shown in viral infections, with peak months from December to February. Patients with influenza infection were likely to be taken to emergency rooms and have respiratory failure with higher creatinine kinase levels and lower white blood cell counts. Streptococcus pneumoniae followed by haemophilus influenzae were the most common bacteria in viral co-infections, which accounted for one third of virus-positive patients. Viral CAP and mixed CAP were not independent factors for death. In addition, lactate dehydrogenase (LDH) >246 IU/L [odds ratio (OR) =7.06, 95% confidence interval (CI): 2.15-23.2, P=0.001], and serum calcium <2.18 mmol/L (OR =6.67, 95% CI: 1.42-31.3, P=0.016) were associated with death., Conclusions: Viruses play an important role in CAP patients with fever, a systematic clinical, radiological and biological analysis of these patients can contribute to effective therapy that may prevent the development of CAP and improve the outcomes. The present work showed an elaborate analysis evidence of viral infection among fever CAP inpatients., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Nonalcoholic fatty liver disease (NAFLD) is a major public health issue worldwide. Immunoglobulin G (IgG) N-glycans are associated with risk factors for NAFLD, such as obesity and diabetes. A cross-sectional study involving 500 Han Chinese adults recruited from a community in Beijing was carried out to explore the association between IgG N-glycans and NAFLD. IgG N-glycosylation was significantly associated with NAFLD, with the disease showing a negative correlation with galactosylation (GP14, GP14n, and G2n), positive correlation with fucosylation (FBG2n/G2n), and positive correlation with bisecting N-acetylglucosamine (GlcNAc) [FBG2n/FG2n and FBG2n/(FG2n+FBG2n)], after controlling age, gender, and prevalence of obesity, type 2 diabetes mellitus, hypertension, and hyperlipidemia. In other words, the present study showed a possible association between NAFLD and the loss of galactose and elevations of fucose and bisecting GlcNAc. Aberrant IgG glycosylation might therefore be a potential biomarker for the primary or secondary prevention of NAFLD., (Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Aim: To investigate whether serum interleukin (IL)-34 levels are correlated with hepatic inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection., Methods: In this study, serum IL-34 levels were assessed by enzyme-linked immunosorbent assay in 19 healthy controls and 175 patients with chronic HBV infection undergoing biopsy. The frequently used serological markers of liver fibrosis were based on laboratory indexes measured at the Clinical Laboratory of the Second Affiliated Hospital of Anhui Medical University. Liver stiffness was detected by transient elastography with FibroTouch. The relationships of non-invasive makers of liver fibrosis and IL-34 levels with inflammation and fibrosis were analyzed. The diagnostic value of IL-34 and other liver fibrosis makers were evaluated using areas under the receiver operating characteristic curves, sensitivity and specificity., Results: Serum IL-34 levels were associated with inflammatory activity in the liver, and IL-34 levels differed among phases of chronic HBV infection ( P = 0.001). By comparing serum IL-34 levels among patients with various stages of liver fibrosis determined by liver biopsy, we found that IL-34 levels ≥ 15.83 pg/mL had a high sensitivity of 86.6% and a specificity of 78.7% for identifying severe fibrosis (S3-S4). Furthermore, we showed that IL-34 is superior to the fibrosis-4 score, one of the serum makers of liver fibrosis, in identifying severe liver fibrosis and early cirrhosis in patients with HBV-related liver fibrosis in China., Conclusion: Our results indicate that IL-34, a cytokine involved in the induction of activation of profibrogenic macrophages, can be an indicator of liver inflammation and fibrosis in patients with chronic HBV infection., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to report.

Objectives: Sarcoidosis is a multisystem disease characterised by the formation of granulomas within various organs, mainly the lungs. Several studies from different countries have been undertaken to investigate sarcoidosis with extrapulmonary involvement except from China. The objective of this study is to investigate a comparative clinical analysis in patients with pulmonary sarcoidosis with and without extrapulmonary involvement from China., Methods: Data from inpatients diagnosed with sarcoidosis at Shanghai Pulmonary Hospital (Shanghai, China) between January 2009 and December 2014 were retrospectively collected and analysed. Six hundred and thirty-six patients with biopsy-proven sarcoidosis were included in the study, including 378 isolated pulmonary sarcoidosis and 258 pulmonary sarcoidosis plus extrapulmonary involvement., Results: Two hundred and fifty-eight (40.6%) patients with pulmonary sarcoidosis had extrapulmonary involvement. Extrapulmonary localisations were detected mostly in extrathoracic lymph nodes (n=147) and skin (n=86). Statistically significant differences were demonstrated between patients with pulmonary sarcoidosis plus extrapulmonary involvement and patients with isolated pulmonary sarcoidosis for fatigue (16.6%vs8.3%, P<0.05), serum ACE (SACE) levels (79.0±46.9 IU/L vs 69.7±38.7 IU/L, P<0.05), and high-resolution CT (HRCT) findings (53.8%vs46.2%, P<0.05)., Conclusions: Extrapulmonary involvement is common in patients with pulmonary sarcoidosis, with the most common sites being extrathoracic lymph nodes and skin. Patients with sarcoidosis with extrapulmonary involvement are more symptomatic (fatigue), have higher SACE levels and more deteriorating HRCT findings, to which clinicians should pay attention., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To investigate the effect of microRNA-125b (miR-125b) on osteogenic differentiation of periodontal ligament stem cell (PDLSCs)., Methods: The surface factor of isolated PDLSCs was detected by flow cytometry. After transfected with miR-125b or anti-miR125b in PDLSCs, MTT and LDH were used to detect cell viability and cytotoxicity; ALP activity and calcium level were detected by ALP assay kit and calcium colorimetric assay kit. Western blot and RT-qPCR were used to determine the expression of osteogenesis-related genes. The interaction between miR-125b and connexin 43 (Cx43) was detected by dual luciferase gene reporter assay. The data were analyzed with SPSS 17.0 software., Results: The cultured PDLSCs showed the characteristics of mesenchymal stem cells. After transfected with miR-125b in PDLSCs, the cell viability was decreased, cytotoxicity was increased; ALP activity, calcium level and the expression of osteogenesis-related genes were significantly decreased. On the contrary, cell viability, ALP activity, calcium level and the expression of osteogenesis-related genes in PDLSCs were increased after anti-miR-125b transfection. Dual luciferase gene reporter assay showed that miR-125b could target Cx43. In addition, the effect of miR-125b on osteogenic differentiation of PDLSCs was reversed after Cx43 overexpression., Conclusions: miR-125b may inhibit osteogenic differentiation of PDLSCs by targeting Cx43.

Purpose: To study the effect of ribosomal S6 kinase (Rsk2) gene on proliferation and osteogenic differentiation of human periodontal ligament cells (hPDLCs) and underlying mechanism., Methods: Premolar surgically extracted were collected, the periodontal ligament was separated and hPDLCs were primarily cultured. Cells of 4 to 6 passage were used in the experiment. The silencing efficiency of small interfering RNA (siRNA) on Rsk2 in hPDLCs was detected by RT-PCR and Western blot. MTT assay was used to detect the effect of Rsk2 siRNA on cell proliferation. Alkaline phosphatase (ALP) kit was used to detect ALP activity. P38MAPK signal pathway inhibitor SB203580 was used to detect hPDLCs after transfection. Western blot was used to detect the effect of Rsk2 siRNA on MAPK signaling pathway p38 protein phosphorylation. The expressions of Runt-related transcription factor-2 (Runx2), osteocalcin (OCN) and osteogenic protein BMP2 were detected by RT-PCR and Western blot. The data were analyzed using SPSS18.0 software package., Results: The expression of Rsk2 was down-regulated by hPDLCs transfected with Rsk2 siRNA, the difference was statistically significant (P<0.05). Rsk2 siRNA significantly reduced phosphorylation of p38 protein (P<0.05), inhibition of hPDLCs proliferation (P<0.05), decreased ALP activity (P<0.01); the expression of Runx2, OCN and BMP2 was different, and the difference was statistically significant (P<0.05). After SB203580 treatment, hPDLCs transfected with Rsk2 siRNA showed increased cell proliferation, ALP activity, Runx2, OCN and BMP2 expression; compared with Rsk2 siRNA transfected hPDLCs, the difference was statistically significant., Conclusions: Rsk2 siRNA inhibits hPDLCs proliferation and osteogenic differentiation through p38MAPK signaling pathway.

To investigate the effect and mechanism of Dracocephalum moldovica total flavones (TFDM) on the formation of atherosclerosis ApoE-/- mice induced by high fat diet. A total of 40 SPF 8-week-old male ApoE-/- mice were fed with high fat diet and randomly divided into 5 groups. TFDM high, medium, low-dose group were given 21, 42, 84 mg•kg⁻¹•d⁻¹ by gavage; Simvastatin group was fed with simvastatin 3.5 mg•kg⁻¹•d⁻¹; and model group was given the same dose of normal saline. The other eight male C57BL/6J mice of the same genetic background and age were set up as control group and fed with common diet. All of the groups were intragastrically intervened for 12 weeks. The aortic pathologic changes were observed with HE; qRT-PCR was adopted to detect TGF-β1, Smad2, Smad3, MMP-2 and MMP-9 gene levels in tissues. Compared with model group, HE staining in TFDM group showed obvious relief of aortic atherosclerotic tissue injury; each TFDM group showed inhibition in mRNA expressions of TGF-β1, Smad2, Smad3, MMP-2 and MMP-9. This suggests that TFDM can inhibit atherosclerosis formation, which may be related to the intervention of TGF-β1/Smads signal transduction., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Background/aims: Acute rejection (AR) is a major complication post renal transplantation, with no widely-accepted non-invasive biomarker. This study aimed to explore the expression profiles of long non-coding RNAs (lncRNAs) in the peripheral blood (PB) of renal transplant recipients and their potential diagnostic values., Methods: The genome-wide lncRNA expression profiles were analyzed in 150 PB samples from pediatric and adult renal transplant (PRTx and ARTx) cohorts. The diagnostic performance of differentially expressed lncRNA was determined using receiver operator characteristic curve, with area under the curve (AUC) and 95% confidential interval (CI). Finally, a risk score was constructed with logistical regression model., Results: A total of 162 lncRNAs were found differentially expressed in PRTx cohort, while 163 in ARTx cohort. Among these identified lncRNAs, 23 deregulated accordingly in both cohorts, and could distinguish AR recipients from those without AR. Finally, a risk score with two most significant lncRNAs (AF264622 and AB209021) was generated and exhibited excellent diagnostic performance in both PRTx (AUC:0.829, 95% CI:0.735-0.922) and ARTx cohorts (AUC: 0.889, 95% CI: 0.817-0.960)., Conclusion: A molecular signature of two lncRNAs in PB could serve as a novel non-invasive biomarker for the diagnosis of AR in both pediatric and adult renal transplant recipients., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Omalizumab, a humanized mAb that binds to IgE, has been an effective therapy for patients with severe allergic asthma; however, there are few clinical trials examining the efficacy of Omalizumab in patients with allergic bronchopulmonary aspergillosis (ABPA) except some case reports. To assess the clinical and immunological effects of Omalizumab in ABPA patients, we made a synthesis review of 102 cases from 30 published literature, analyzed the effects of Omalizumab therapy in ABPA and conducted subgroup analyses to determine factors that influenced the therapy endpoints. We found that Omalizumab treatment not only provided a clinically important reduction in serum IgE, exacerbation rates and steroid requirement, but also showed attenuated asthma symptoms and improved pulmonary function parameters in patients with ABPA. Moreover, further discussion was made when interpretating the results. Double-blind, randomized, placebo-controlled trials are necessary to establish the efficacy and safety of this novel therapeutic intervention for ABPA patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Increasing evidence supports the anticancer effects of morin in vitro and in vivo. However, the role of morin-7-sulphate sodium (NaMoS), a water-soluble flavonoid derivative synthesized from morin remains unclear. The present study investigated the tumor suppression by NaMoS in mouse melanoma cells., Materials and Methods: We synthesized the flavonoid derivative morin-7-sulphate sodium according to the method described for quercetin-sulphate derivative, and further isolated, purified and identified the compound. Cell proliferation in vitro was assessed using a CCK-8 assay. The wound healing assay was performed to evaluate cell motility, and flow cytometry was used to detect cellular apoptosis. Protein levels of vimentin, matrix metalloproteinase 9 (MMP9), phosphorylation of Akt1/2/3 (p-Akt1/2/3), extracellular signal-regulated kinase 1/2 (p-ERK1/2) and Caspase3 in B16F10 cells were detected by immunohistochemistry and Western blot., Results: The results suggest that cell proliferation was markedly decreased in NaMoS-treated groups (1, 10, 25, 50, 100, 500, 1000μM) in a dose-dependent manner compared with the Control group and the IC 50 was 221.67μM at 48h. NaMoS at 200μM concentration significantly inhibited the invasion and promoted apoptosis of B16F10 cells. Moreover, protein level of Caspase3 increased significantly in B16F10 cells treated by NaMoS. Immunohistochemistry and Western blot further confirmed that NaMoS decreased the expression of vimentin, MMP9, p-Akt1/2/3 and p-ERK1/2 in B16F10 cells., Conclusions: This study provides robust evidence that NaMoS, a water-soluble flavonoid, manifests anticancer properties and may act as a signal transduction inhibitor in melanoma cells., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Early diagnosis of nasopharyngeal carcinoma (NPC) needs more reliable biomarkers. The aim of this study was to investigate serum cytokeratin 19 fragment 21.1 (CYFRA21-1) as an NPC biomarker based on data from a large sample., Methods: From October 2010 to February 2014, 529 subjects were enrolled and divided into three groups-NPC group (n = 274), healthy control group (n = 175) and nasal inflammatory disease group (n = 80). Serum CYFRA21-1 levels were measured prior to radiotherapy/chemoradiotherapy, and their associations with T, N, and clinical classification were determined. Receiver operating characteristic curve analysis was performed to discriminate the NPC group from the healthy control and nasal inflammatory disease groups. Three Epstein-Barr virus (EBV) antibodies and their correlations with serum CYFRA21-1 levels were analyzed., Results: Pretreatment serum CYFRA21-1 levels were significantly elevated in the NPC group compared with the other groups (p < 0.01), Furthermore, serum CYFRA21-1 levels decreased significantly after radiotherapy (p < 0.01). Serum CYFRA21-1 levels were closely related to T, N, and clinical classifications. The area under the curve, sensitivity and specificity of the serum CYFRA21-1 levels in the NPC patients were 0.89, 0.87 and 0.83, respectively. Strong correlations were observed between serum CYFRA21-1 levels and EBV antibodies., Conclusion: Serum CYFRA21-1 may be a reliable and effective biomarker for NPC.

Objective: To investigate the expression of N-cadherin in bone marrow leukemic cells derived from acute leukemia patients and its clinical significances., Methods: A total of 113 patients with acute leukemia were enrolled in this study. Flow cytometry was employed to detect the expression of N-Cadherin in bone marrow leukemic cells from acute leukemia patients and the relationships between the N-cadherin expression and the clinical characteristics of patients with acute leukemia were analyzed., Results: The expression of N-Cadherin in bone marrow leukemic cells deriveted from patients with acute leukemia was variable with 0%-99.7%. For adult AML patients, the positive rate of CD34 in N-cadherin + group was significantly higher than that in N-cadherin - group(67.39% vs 33.33%)(P=0.013), while the differences of total CR rate and rate of CR after 1 cycle of induction treatment were not significant between these 2 groups(P>0.05). As to ALL patients, N-cadherin + group had significant lower WBC count (21.31±7.07 vs 51.10±23.69)(P=0.008) and lower percentage of peripheral blood blast (43.22±5.75% vs 66.45±5.65%)(P=0.015). The CR rate after 1 cycle of induction treatment and rate of overall CR were lower and the relapse rate was higher in N-cadherin + ALL group than those in N-cadherin - ALL group, but the differences were not significant (P>0.05). For childhood ALL, the positive rate of CD33 in N-cadherin + group was significantly higher than that in N-cadherin - group(47.62% vs 0%)(P=0.012). The relapse rate was higher in N-cadherin + group than that in N-cadherin - group (30.00% vs 0%)(P=0.115). The median survival time, 3-year overall OS rate and 3-year relapse-free survival rate in N-cadherin - groups of adult AML, non-M3 AML, ALL and chidhood ALL paients were superior to N-cadherin + groups, but the differences were not significant., Conclusion: The expression of N-cadherin in bone marrow leukemic cells relates to some clinical features of patients with acute leukemia and to some extent has inferior effect on survival of patients with acute leukemia.

The development of food-grade (nano)particles as a delivery system for poorly water soluble bioactives has recently attracted increasing attention. This work is an attempt to fabricate food protein-based nanoparticles as delivery systems for improving the water dispersion and bioaccessibility of phytosterols (PS) by an emulsification-evaporation method. The fabricated PS nanoparticles were characterized in terms of particle size, encapsulation efficiency (EE%) and loading amount (LA), and ξ-potential. Among all the test proteins, including soy protein isolate (SPI), whey protein concentrate (WPC) and sodium caseinate (SC), SC was confirmed to be the most suitable protein for the PS nano-formulation. Besides the type of protein, the particle size, EE% and LA of PS in the nanoparticles varied with the applied protein concentration in the aqueous phase and organic volume fraction. The freeze-dried PS nanoparticles with SC exhibited good water re-dispersion behavior and low crystallinity of PS. The LA of PS in the nanoparticles decreased upon storage, especially at high temperatures (e.g., >25 °C). The PS in the fabricated nanoparticles exhibited much better bioaccessibility than free PS. The findings would be of relevance for the fabrication of food-grade colloidal phytosterols, with great potential to be applied in functional food formulations.

As a newly discovered tumor-specific gene, p42.3 is overexpressed in most of human gastric cancers (GC). However, the role of p42.3 in GC progression remains unclear. To assess the role of p42.3 in gastric cancers, immunohistochemistry and western blot were performed to detect the p42.3 expression in human GC tissues and cells. We also investigated the role of p42.3 in GC cell proliferation, migration, and invasion. Our results showed that the p42.3 expression was increased dramatically in human GC tissue and cells. In addition, we found that overexpression of p42.3 promotes GC cell proliferation, migration, and invasion abilities. Furthermore, p42.3 expression suppressed the E-cadherin protein level and promoted the β-catenin and p-ERK protein level. Taken together, overexpressed p42.3 is correlated with gastric cancer cell proliferation, migration, and invasion, suggesting its use as a biological marker in gastric cancer.

We aimed to investigate the association between dihydropyrimidine dehydrogenase (DPYD) gene polymorphisms and the risk of pediatric acute lymphoblastic leukemia (ALL) and its prognosis after chemotherapy. A total of 147 pediatric ALL patients diagnosed by our hospital between January 2011 and December 2014 were included in the case group, and 102 healthy people who received a physical examination during the same time frame in our hospital were included in the control group. DNA sequencing was applied for site determination and genotyping of the DPYD 85T > C, 2194G > A, 1156G > T, and IVS14 + 1G > A polymorphisms. The genotype and allele frequencies of the two groups were compared. A significant difference was found in the comparison of the mutant gene and allele frequencies of the 85T > C polymorphism between the case and control groups (P < 0.05). The CT and CC genotypes in the 85T > C polymorphism were associated with the risk of the disease (OR = 1.592, 95 % CI = 1.010-2.509), suggesting that the recessive gene (85C) was more likely to lead to the occurrence of ALL compared with the dominant gene (85T) (P < 0.05). Patients carrying the C allele of the 85T > C polymorphism presented higher damage of their liver functions and higher infection rates compared with patients carrying the non-C allele (P < 0.05). A higher proportion of liver function damage and a higher infection rate were found in patients with the GA genotype in the IVS14 + 1G > A polymorphism compared with the GG genotype (P < 0.05). The complete remission (CR) rate in patients with the GG genotype in the IVS14 + 1G > A polymorphism was higher than in patients with the GA genotype (P = 0.020). After 5-fluorouracil/calcium folinate (5-FU/CF)-based chemotherapy, the event-free survival (EFS) rate of patients with the TT genotype was higher than patients with the CT and CC genotypes (P < 0.05). Our results revealed that the C allele of the 85T > C polymorphism might be associated with susceptibility to pediatric ALL. Patients carrying the C allele may have an increased risk of ALL. Thus, the 85T > C polymorphism may be a predictor of CR for pediatric ALL patients.

Objective: To analyze the clinical characteristics of cytomegalovirus(CMV) infection after allogenic hematopoietic stem cell transplantation(allo-HSCT) and the effect of preemptive therapy., Methods: A total of 134 patients who underwent allo-HSCT from March 2010 to March 2015 in the Department of Hematology of our hospital were enrolled in this study. The CMV infection rate, the median time of CMV infection occurence, and the risk factors for CMV infection after allo-HSCT, the response rate of preemptive treatment and the median time of CMV-DNA turning negative were analyzed. Five-year overall survival rate was compared between the patients with or without CMV infection., Results: The incidence of CMV viremia was 55.2％(74／134), and the median time for the CMV with CMV-DNA positive for the first time was 34 days(14-283) after allo-HSCT．Both univariate and multivariate analysis showed that the thymoglobulin(ATG) used in conditioning regimen and Ⅱ-Ⅳ grade of aGVHD were the risk factors for CMV viremia. After preemptive treatment the 85.1% of patient with CMV viremia turned negative, and the median time of CMV-DNA turning negative were 15 days(5-82), only 2 patients died of CMV pneumonia. Five-year overall survival rate of the patients with or wihout CMV viremia was 49% and 66.3% respectively, and the difference between the 2 groups was significant(P=0.041）., Conclusion: The ATG used in conditioning regimen and Ⅱ-Ⅳ grade of aGVHD may increase the incidence of CMV infection after allo-HSCT, and the preemptive thrapy can effectively prevent the CMV viremia turning to CMV disease.

Background: Pulmonary Langerhans cell histiocytosis (PLCH) is an orphan disease in respiratory medicine, which most affects adult smokers. The purpose of this article was to discuss the clinical features, especially the radiologic features of PLCH patients during their hospitalization through a retrospective analysis on clinical data. Furthermore, the current literature was also reviewed., Methods: Between December 2008 and June 2012, 14 patients with PLCH were assessed at Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. Among these patients, seven patients were diagnosed through tissue biopsy from the lung and one patient from enlarged cervical lymph nodes; the rest of six patients were diagnosed based on the clinical-radiological data. The data consisting of demographics, clinical presentation, smoking habits, pulmonary function tests (PFTs) and radiographic image from the medical records was analyzed retrospectively., Results: The average age of patients (11 males and 3 females) was 42.79 (±13.71) years old. All male patients and one female patient had a long smoking history. The common manifestations were cough and exertional dyspnea. Spontaneous pneumothorax was found in three patients. Varieties of pulmonary shadows such as nodular, cystic, patch-like and cord-like were revealed by chest computed tomography (CT) examination. Large Langerhans cells (LCs) were discovered in biopsy tissue by immunohistochemical stains., Conclusions: PLCH is still an orphan disease and maybe related to smoking. Clinical symptoms such as cough and exertional dyspnea are non-specific. We shall pay attention to recurrent pneumothorax as clinically it is associated with PLCH. The characteristic radiological manifestation is cystic or nodular shadow in the lungs, which plays crucial roles in diagnosing PLCH.

Ocular toxocariasis (OT) is a zoonotic parasitic infection mainly caused by the intraocular tissue invasion of second-stage Toxocara canis or Toxocara cati larva. Measuring specific anti-T. canis antibodies in the intraocular fluid (IF) can increase OT diagnosis accuracy using Goldmann-Witmer coefficient (GWC). However, there is no systemic evaluation of GWC application in the immunological diagnosis of OT. To assess GWC for the immunodiagnosis of ocular toxocariasis, paired IF and serum samples from 72 patients diagnosed with OT were retrospectively analyzed for specific anti-T. canis IgG by enzyme linked immunosorbent assay (ELISA). GWC values were calculated to determine intraocular specific IgG production. Clinical features and other laboratory data were recorded, and their correlations with GWC evaluated. Of the 72 OT patients, 60 (83.33%) showed intraocular specific IgG production confirmed by GWC, while intraocular nonspecific IgE production was found in 64/69 (92.75%) cases. No significant correlation was found among clinical features and IF specific IgG production. Values for peripheral blood samples were lower than those of intraocular fluid regarding OT screening, and vitreous humor samples showed increased local specific IgG and nonspecific IgE production compared with aqueous humor samples. Overall, our results indicate that GWC and intraocular IgE production have referential values in diagnosing ocular toxocariasis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Buchnera aphidicolais an obligate endosymbiont that provides aphids with several essential nutrients. Though much is known about aphid-Buchnera interactions, the effect of the host plant on Buchnera population size remains unclear. Here we used quantitative PCR (qPCR) techniques to explore the effects of the host plant on Buchnera densities in the cotton-melon aphid, Aphis gossypii Buchneratiters were significantly higher in populations that had been reared on cucumber for over 10 years than in populations maintained on cotton for a similar length of time. Aphids collected in the wild from hibiscus and zucchini harbored more Buchnera symbionts than those collected from cucumber and cotton. The effect of aphid genotype on the population size of Buchnera depended on the host plant upon which they fed. When aphids from populations maintained on cucumber or cotton were transferred to novel host plants, host survival and Buchnera population size fluctuated markedly for the first two generations before becoming relatively stable in the third and later generations. Host plant extracts from cucumber, pumpkin, zucchini, and cowpea added to artificial diets led to a significant increase in Buchnera titers in the aphids from the population reared on cotton, while plant extracts from cotton and zucchini led to a decrease in Buchnera titers in the aphids reared on cucumber. Gossypol, a secondary metabolite from cotton, suppressed Buchnera populations in populations from both cotton and cucumber, while cucurbitacin from cucurbit plants led to higher densities. Together, the results suggest that host plants influence Buchnera population processes and that this may provide phenotypic plasticity in host plant use for clonal aphids., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Polydatin (PD), a natural precursor of resveratrol, has a variety of biological activities, including anti‑tumor effects. However, the underlying molecular mechanisms of the anti-cancer activity of PD has not been fully elucidated. The present study demonstrated that PD significantly inhibited the proliferation of the MOLT-4 leukemia cell line in a dose‑ and time-dependent manner by using Cell Counting Kit‑8 assay. PD also dose-dependently increased the apoptotic rate and caused cell cycle arrest in S phase in MOLT‑4 cells, as revealed by flow cytometry. In addition, PD dose-dependently decreased the mitochondrial membrane potential and led to the generation of reactive oxygen species in MOLT-4 cells. Western blot analysis revealed that the expression of anti‑apoptotic protein B-cell lymphoma 2 (Bcl-2) was decreased, whereas that of pro‑apoptotic protein Bcl‑2‑associated X was increased by PD. Furthermore, the expression of two cell cycle regulatory proteins, cyclin D1 and cyclin B1, was suppressed by PD. Of note, the pro‑apoptotic and cell cycle‑inhibitory effects of PD were potentiated by Janus kinase 2 (JAK2) inhibition. In conclusion, the results of the present study strongly suggested that PD is a promising therapeutic compound for the treatment of leukemia, particularly in combination with JAK inhibitors.

Introduction: Presence of white matter hyperintensity (WMH) on MRI is a marker of cerebral small vessel disease and is associated with increased small vessel stroke and increased risk of hemorrhagic transformation (HT) after thrombolysis., Aim: We sought to determine whether white matter hypoperfusion (WMHP) on perfusion CT (CTP) was related to WMH, and if WMHP predisposed to acute lacunar stroke subtype and HT after thrombolysis., Methods: Acute ischemic stroke patients within 12 h of symptom onset at 2 centers were prospectively recruited between 2011 and 2013 for the International Stroke Perfusion Imaging Registry. Participants routinely underwent baseline CT imaging, including CTP, and follow-up imaging with MRI at 24 h., Results: Of 229 ischemic stroke patients, 108 were Caucasians and 121 Chinese. In the contralateral white matter, patients with acute lacunar stroke had lower cerebral blood flow (CBF) and cerebral blood volume (CBV), compared to those with other stroke subtypes (P = 0.041). There were 46 patients with HT, and WMHP was associated with increased risk of HT (R(2) = 0.417, P = 0.002). Compared to previously reported predictors of HT, WMHP performed better than infarct core volume (R(2) = 0.341, P = 0.034), very low CBV volume (R(2) = 0.249, P = 0.026), and severely delayed perfusion (Tmax>14 second R(2) = 0.372, P = 0.011). Patients with WMHP also had larger acute infarcts and increased infarct growth compared to those without WMHP (mean 28 mL vs. 13 mL P < 0.001)., Conclusion: White matter hypoperfusion remote to the acutely ischemic region on CTP is a marker of small vessel disease and was associated with increased HT, larger acute infarct cores, and greater infarct growth., (© 2016 John Wiley & Sons Ltd.)

Background: Many epidemiologic studies have documented variable relationships between ambient particulate matter (PM) and COPD hospitalizations and mortality in cities worldwide., Methods: Comprehensive and systematic searches were performed in the electronic reference databases (PubMed, EMBASE, Google Scholar, Ovid, and Web of Science) with specific search terms and selection criteria for relevant studies. Summary ORs and 95% CIs were calculated to evaluate the relationship between short-term exposure to PM with aerodynamic diameters ≤ 2.5 μm (PM2.5) and COPD hospitalizations and mortality. The sources of heterogeneity and the effect of potential confounders were explored using subgroup analyses. Study findings were analyzed using a random effects model and a fixed effects model in COPD hospitalizations and mortality, respectively., Results: The search yielded 12 studies suitable for meta-analysis of hospitalizations and six studies suitable for the mortality meta-analysis until April 15, 2015. A 10-μg/m(3) increase in daily PM2.5 (lag days 0-7) was associated with a 3.1% (95% CI, 1.6%-4.6%) increase in COPD hospitalizations and a 2.5% (95% CI, 1.5%-3.5%) increase in COPD mortality. Significant publication bias was not found in studies focusing on the relationship between short-term PM2.5 exposure and COPD hospitalizations and mortality., Conclusions: Our combined analysis indicated that short-term exposure to a 10-μg/m(3) increment of ambient PM2.5 is associated with increased COPD hospitalizations and mortality. Further study is needed to elucidate to what extent this relationship is causal, together with other factors, and to elucidate the mechanism by which PM2.5 induces activation of cellular processes promoting COPD exacerbations., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Diabetic nephropathy (DN) remains one of the most common causes of end-stage renal disease. Current therapeutic strategies aiming at optimization of serum glucose and blood pressure are beneficial in early stage DN, but are unable to fully prevent disease progression. With the limitations of current medical therapies and the shortage of available donor organs for kidney transplantation, the need for novel therapies to address DN complications and prevent progression towards end-stage renal failure is crucial. The development of ultrasound technology for non-invasive and targeted in-vivo gene delivery using high power ultrasound and carrier microbubbles offers great therapeutic potential for the prevention and treatment of DN. The promising results from preclinical studies of ultrasound-mediated gene delivery (UMGD) in several DN animal models suggest that UMGD offers a unique, non-invasive platform for gene- and cell-based therapies targeted against DN with strong clinical translation potential.

Foot-and-mouth disease is a highly contagious viral disease of cloven-hoofed animals that is caused by foot-and-mouth disease virus (FMDV). To replicate efficiently in vivo, FMDV has evolved methods to circumvent host antiviral defense mechanisms, including those induced by interferons (IFNs). Previous research has focused on the effect of FMDV L(pro) and 3C(pro) on type I IFNs. In this study, FMDV VP3 was found to inhibit type II IFN signaling pathways. The overexpression of FMDV VP3 inhibited the IFN-γ-triggered phosphorylation of STAT1 at Tyr701 and the subsequent expression of downstream genes. Mechanistically, FMDV VP3 interacted with JAK1/2 and inhibited the tyrosine phosphorylation, dimerization and nuclear accumulation of STAT1. FMDV VP3 also disrupted the assembly of the JAK1 complex and degraded JAK1 but not JAK2 via a lysosomal pathway. Taken together, the results reveal a novel mechanism used by which FMDV VP3 counteracts the type II IFN signaling pathways.

Background: It was reported that Cathepsin E (Cat E) plays a critical role in antigen processing and in the development of pulmonary emphysema. The aim of this study was to investigate the role of Cat E and airflow limitation in the pathogenesis of COPD., Methods: Sixty-five patients with COPD, 20 smoking control subjects without COPD and 15 non-smoking healthy control subjects were enrolled. Cat E and EIC (Elastase inhibitory capacity) expressions were measured by ELISA in sputum and serum samples and compared according to different subgroups., Results: Cat E concentrations were significantly higher in patients with COPD than smoking control and non-smoking control subjects (P < 0.01). The levels of CatE were inversely correlated with FEV1% predicted in COPD patients (r = -0.95, P < 0.01). The levels of EIC were inversely positively correlated with FEV1% predicted in COPD patients (r = 0.926, P < 0.01). Levels of Cat E were also inversely correlated with the levels of EIC (r = -0.922, P < 0.01)., Conclusions: Cat E contributes to the severity of airflow limitation during progression of COPD.

Objective: MicroRNAs are involved in many critical functions, including angiogenesis. Ultrasound-targeted microbubble destruction (UTMD) is a noninvasive technique for targeted vascular transfection of plasmid DNA and may be well suited for proangiogenic microRNA delivery. We aimed to investigate UTMD of miR-126-3p for therapeutic angiogenesis in chronic ischemia., Approach and Results: The angiogenic potential of miR-126-3p was tested in human umbilical vein endothelial cells in vitro. UTMD of miR-126-3p was tested in vivo in Fischer-344 rats before and after chronic left femoral artery ligation, evaluating target knockdown, miR-126-3p and miR-126-5p expression, phosphorylated Tie2 levels, microvascular perfusion, and vessel density. In vitro, miR-126-3p-transfected human umbilical vein endothelial cells showed repression of sprouty-related protein-1 and phosphatidylinositol-3-kinase regulatory subunit 2, negative regulators of vascular endothelial growth factor and angiopoietin-1 signaling, increased phosphorylated Tie2 mediated by knockdown of phosphatidylinositol-3-kinase regulatory subunit 2 and greater angiogenic potential mediated by both vascular endothelial growth factor/vascular endothelial growth factor R2 and angiopoietin-1 /Tie2 effects. UTMD of miR-126-3p resulted in targeted vascular transfection, peaking early after delivery and lasting for >3 days, and resulting in inhibition of sprouty-related protein-1 and phosphatidylinositol-3-kinase regulatory subunit 2, with minimal uptake in remote organs. Finally, UTMD of miR-126-3p to chronic ischemic hindlimb muscle resulted in improved perfusion, vessel density, enhanced arteriolar formation, pericyte coverage, and phosphorylated Tie2 levels, without affecting miR-126-5p or delta-like 1 homolog levels., Conclusions: UTMD of miR-126 results in improved tissue perfusion and vascular density in the setting of chronic ischemia by repressing sprouty-related protein-1 and phosphatidylinositol-3-kinase regulatory subunit 2 and enhancing vascular endothelial growth factor and angiopoietin-1 signaling, with no effect on miR-126-5p. UTMD is a promising platform for microRNA delivery, with applications for therapeutic angiogenesis., (© 2015 American Heart Association, Inc.)

Anti-EGFR monoclonal antibodies (mAb) such as cetuximab, panitumumab are one kind of efficacious targeted drugs in treatment of metastatic colorectal cancer (mCRC). However, only a small proportion of patients harbored wild-KRAS genotype can benefit from it. We hypothesized that personal genetic heterogeneity might be the main cause leading to obvious difference in its clinical efficacy. A retrospective study including 82 mCRC patients treated with chemotherapy plus cetuximab and a comprehensive meta-analysis containing 2831 cases within sixteen eligible studies were conducted to investigate the possible association between FCGR2A H131R and FCGR3A V158F and clinical outcome of mCRC patients treated with anti-EGFR mAb based therapy. Results of the retrospective study showed that H131R within FCGR2A or V158F within FCGR3A were not associated with clinical outcome in 82 KRAS wild chemorefractory mCRC patients in co-dominant, dominant, recessive, over-dominant, allele genetic models. However, the comprehensive meta-analysis with the largest of sample size obtained the significant result between FCGR3A V158F and PFS (FV/VV vs. FF: Ph = 0.027, MSR = 0.680, 95%CI = 0.549-0.842 in overall population; Ph = 0.12, MSR = 0.728, 95%CI = 0.648-0.818 in KRAS wild population) and OS (VV vs. FF: Ph < 0.001, MSR = 0.733, 95%CI = 0.578-0.930 in overall population). These findings indicate that KRAS wild chemorefractory mCRC individual harbored genotype FF of V158Fcan benefit from anti-EGFR mAb adjuvant therapy in terms of PFS and OS, and it may be useful genetic biomarker to predict clinical survival of mCRC individuals with anti-EGFR mAb based therapy.

Purpose: Photodynamic therapy (PDT) is a promising treatment in cancer therapy, based on the use of a photosensitizer activated by visible light in the presence of oxygen. Nowadays significant research efforts have been focused on finding a new photosensitizer. In the present paper, the antitumor effects of a novel porphyrin-based photosensitizer, {Carboxymethyl-[2-(carboxymethyl-{[4-(10,15,20-triphenylporphyrin-5-yl)-phenylcarbamoyl]-methyl}-amino)-ethyl]-amino}-acetic acid (ATPP-EDTA) on two types of human malignant tumor cells in vitro and a gastric cancer model in nude mice, were evaluated., Methods: The PDT efficacy with ATPP-EDTA in vitro was assessed by MTT assay. The intracellular accumulation was detected with fluorescence spectrometer, and the intracellular distribution was determined by laser scanning confocal microscopy. The mode of cell death was investigated by Hoechst 33342 staining and flow cytometer. BGC823-derived xenograft tumor model was established to explore the in vivo antitumor effects of ATPP-EDTA., Results: ATPP-EDTA exhibited intense phototoxicity on both cell lines in vitro in concentration- and light dose-dependent manners meanwhile imposing minimal dark cytotoxicity. The accumulation of ATPP-EDTA in two malignant cell lines was time-dependent and prior compared to normal cells. It was mainly localized at lysosomes, but induced cell death by apoptotic pathway. ATPP-EDTA significantly inhibited the growth of BGC823 tumors in nude mice (160 mW/cm(2), 100 J/cm(2))., Conclusions: Present studies suggest that ATPP-EDTA is an effective photosensitizer for PDT to tumors. It distributed in lysosomes and caused cell apoptosis. ATPP-EDTA, as a novel photosensitizer, has a great potential for human gastric cancer treatment in PDT and deserves further investigations.

p21-Activated kinase 5 (PAK5) is the last identified member of the PAK family. The PAKs are highly conserved serine/threonine and effector proteins for Cdc42 and Rac and are essential in regulating cell motility and survival. Previous studies have demonstrated that PAK5 played a pivotal role in apoptosis, proliferation, cancer migration, and invasion. However, the biological function of PAK5 in hepatocellular carcinoma, as well as its underlying mechanism, still remains to be fully elucidated. In the present study, we demonstrated that PAK5 markedly inhibited cisplatin-induced apoptosis and promoted cell proliferation in hepatocellular carcinoma cells. Moreover, our results showed that overexpression of PAK5 contributed to cell cycle regulation. In order to elucidate the underlying mechanism of PAK5 on cisplatin-induced apoptosis and cell cycle regulation, we also examined the protein expressions of chk2 and p-chk2. In summary, our study investigated the role of PAK5 in cisplatin-induced cellular processes and provided evidence of its underlying mechanism.

Unlabelled: We investigated if the serum cytokeratin 19 fragment 21.1 (CYFRA21-1) level was elevated in nasopharyngeal carcinoma (NPC) and can function as a biomarker for detection and monitoring of NPC. Three hundred and one study subjects were divided into two groups: the NPC group (n=126) and healthy control group (n=175). Serum CYFRA21-1 levels were measured before and after treatment using a chemiluminescent immunoassay, and its association with tumor stage and the clinical objective responses were analyzed. Receiver operating characteristic (ROC) curve analysis was performed to discriminate patients with NPC from the healthy controls. The pretreatment serum CYFRA21-1 level was significantly elevated in patients with NPC compared with the healthy controls (5.07±1.98 ng/ml vs 2.36±1.21 ng/ml, p<0.001), and it declined significantly after the entire treatment (2.14±0.72 ng/ml, p<0.001). The serum CYFRA21-1 level of patients with a classification of T3-4 was significantly higher than that of those with class T1-2 (5.64±2.23 ng/ml vs 4.62±1.64 ng/ml, p=0.006), and that of patients with clinical stage III-IV was higher than clinical stage I-II (5.31±2.02 vs 4.04±1.37 ng/ml, p=0.003). The AUC, sensitivity and specificity of elevated serum CYFRA21-1 in patients with NPC was 0.91, 0.83 and 0.89 respectively. In conclusion, the serum CYFRA21-1 level could be a reliable and effective biomarker for the detection and monitoring of NPC tumor progression., Keywords: nasopharyngeal carcinoma, CYFRA21-1, tumor biomarker, receiver operating characteristic curve.

As a newly discovered tumor-associated gene, p42.3 was originally ascertained in gastric cancer cell line BGC823 and has been confirmed as a cell cycle-dependent gene that is overexpressed in many human tumor cell lines and embryonic tissues. p42.3 can regulate the level of relevant cycle-dependent proteins and promote malignant transformation of cells. A variety of cellular functions, including cell proliferation, cell invasion and cell migration, are under control of p42.3. Our review, namely the introduction of the structure of p42.3, underlying activity regulation mechanisms of p42.3 as well as the role p42.3 plays in malignant cellular transformation process, are accompanied by the presentation of potential directions of further researches of cancer prevention and therapy in which p42.3 is inevitable.

p42.3 is a tumor-specific gene and found to be over-expressed in many tumor cell lines and primary tumor tissues. It plays a significant role in neoplastic transformation and tumor progression. To date, the association between p42.3 and Renal-Cell Carcinoma (RCC) has not been reported. This study investigated the biological effects and mechanisms of p42.3 in RCC progression. In this study, we found that p42.3 is overexpressed in various kinds of RCC cells, and knockdown of p42.3 dramatically reduced cell proliferation and invasion in vitro. Our studies revealed that overexpression of p42.3 accelerates the epithelial-mesenchymal transition (EMT) progression and induces RCC cells proliferation and invasion. Further studies show that p42.3 may involve in activation of β-catenin and participate in RCC cell invasion. Combined, these data indicate that p42.3 contributes to promoting RCC cells proliferation and invasion through accelerates the EMT progression and β-catenin activation.

RIG-I-like receptors (RLRs) belong to pattern recognition receptors, which perform significant roles in antiviral responses. RLRs can initiate a cascade of signaling transduction that induces the production of type I interferon and activates the interferon signaling pathway, ultimately resulting in antiviral responses. In the course of evolution, viruses have been constantly counteracting host immune systems to facilitate their own survival and replication, and have developed a set of antagonistic strategies. These mainly comprise elusion, disguise and attack strategies to eliminate the activation of RLRs. In virus-infected cells, RLRs recognize viral RNA and then induce antiviral responses. A better understanding of viral antagonistic strategies against RLRs will provide insights into the development of new antiviral medicines. This mini-review concludes that there are three main antagonistic strategies by which RNA viruses can counteract the activation of the RLRs pathway. It aims to provide references and insights for similar studies on viral antagonism in an array of RNA viruses.

The aim of this study was to explore the reversing effect of cinobufacini on multidrug resistance of Raji/ADR cells and its mechanisms. The growth inhibitory rate, half inhibitory concentration (IC50), reversing multiples to adriamycin- resistance were detected by MTT, and the curve of growth inhibitory rate was drawn; the MDR-1 and MRP-1 gene transcription was determined by RT-PCR; the expressions of P-gp and MRP-1 proteins were assayed by Western blot and flow cytometry. The results showed that the inhibitory rates of cinobufacini on Raji and Raji/ADR cells at 72 h were 75.6% and 69.3% respectively, the IC50 were 3.9 mmol/L and 4.6 mmol/L without significant difference (P > 0.05). The reversing multiples to adriamycin-resistance were 255.7 multiples, the transcription of mdr-1 and mrp-1 genes and the expression of P-gp and MRP-1 proteins significantly decreased (P < 0.05) in Raji/ADR cells after the treatment with cinobufotalin. It is concluded that cinobufotalin can reverse the adriamycin-resistance in Raji/ADR cells and the expression of P-gp and MRP-1 proteins were down-regulated through the transcriptional pathway. The cinobufotalin is an effective reversal agent for the multidrug resistance of tumors.

Guanylate-binding protein 1 (GBP1) is an interferon induced protein, that belongs to the guany late-binding protein family. GBP1 is widely involved in anti-infection immune responses, anti-tumor activity and various biological reactions. Recent studies have proved that IFN-alpha, IFN-beta, IFN-gamma, IL1alpha, IL1beta, TNF-alpha and LPS can induce GBP1 expression; hence, the diverse biological functions of GBP1 have been gradually deduced and exploited. Many studies have been performed over recent years to understand the exact mechanisms that underlie the anti-infection and anti-tumor properties of GBP1. This review describes the molecular structure, biological activity, anti-infective properties and other functions of GBP1, in order to provide insights into the divergent roles of GBP1 in the regulation of various biological processes.

Reverse-genetic engineering of foot and mouth disease virus (FMDV) can improve the productivity, antigen matching, antigen stability, immune response ability, and biological safety of vaccines, so vaccine candidates with anticipated biological characteristics can be promptly achieved. Negative influence in taming of virulent strains can also be decreased or avoided. Reverse genetics not only make up for deficiencies like limitation of viral nature, low success rate, and time and energy consuming, but also realize more active designing of vaccines. Therefore, reverse genetics is significant in improving integral quality and efficiency of vaccines. In this review, we use FMDV vaccines as an example to summarize improvement in biological characteristics of virulent strains and provide a reference for related researches.

Background: Resveratrol is a natural compound that affects energy metabolism and is also known to possess an array of cardioprotective effects. However, its overall effects on energy metabolism and the underlying mechanism involved in cardioprotection require further investigation. Herein we hypothesize that ATP-sensitive potassium (K-ATP) channels as molecular sensors of cellular metabolism may mediate the cardioprotective effects of resveratrol., Methods: Kir6.2 knockout, Kir6.1 heterozygous and wild-type (WT) mice were subjected to ischemia/reperfusion injury and were injected with resveratrol (10 mg/kg, i.p). Myocardial infarct size, serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities were determined. Neonatal cardiomyocytes were used in in vitro assays to investigate the underlying mechanism of resveratrol in cardioprotection., Results: Resveratrol treatment significantly reduced myocardial infarct size and serum LDH and CK activity and inhibited oxygen-glucose deprivation/reoxygenation - induced cardiomyocyte apoptosis in WT and Kir6.1 heterozygous mice, but Kir6.2 deficiency can abolish the cardioprotective effects of resveratrol in vivo and in vitro. We further found that resveratrol enhanced 5'-AMP-activated protein kinase (AMPK) phosphorylation and promoted the association of AMPK with Kir6.2. Suppression of AMPK attenuated and activation of AMPK mimicked the cardioprotective effects of resveratrol in cardiomyocytes. Notably, Kir6.2 knockout also reversed the cardioprotection of AMPK activator., Conclusions: Our study demonstrates that resveratrol exerts cardioprotective effects through AMPK -Kir6.2/K-ATP signal pathway and Kir6.2-containing K-ATP channel is required for cardioprotection of resveratrol.

Background: The widespread use of clopidogrel alone or in combination with aspirin may result in gastrointestinal mucosal injury, clinically represented as recurrent ulceration and bleeding complications. Our recent work suggested that clopidogrel significantly induced human gastric epithelial cell (GES-1) apoptosis and disrupted gastric mucosal barrier, and that a p38 MAPK inhibitor could attenuate such injury. However, their exact mechanisms are largely unknown., Methods: The GES-1 cells were used as a model system, the effects of clopidogrel on the whole gene expression profile were evaluated by human gene expression microarray and gene ontology analysis, changes of the mRNA and protein expression were determined by real-time PCR and Western blot analysis, and cell viability and apoptosis were measured by MTT assay and flow cytometry analysis, respectively., Results: Gene microarray analysis identified 79 genes that were differentially expressed (P<0.05 and fold-change >3) when cells were treated with or without clopidogrel. Gene ontology analysis revealed that response to stress and cell apoptosis dysfunction were ranked in the top 10 cellular events being affected, and that the major components of endoplasmic reticulum stress-mediated apoptosis pathway - CHOP and TRIB3- were up-regulated in a concentration- and time-dependent manner when cells were treated with clopidogrel. Pathway analysis demonstrated that multiple MAPK kinases were phosphorylated in clopidogrel-treated GES-1 cells, but that only SB-203580 (a p38-specific MAPK inhibitor) attenuated cell apoptosis and CHOP over-expression, both of which were induced by clopidogrel., Conclusions: Increased endoplasmic reticulum stress response is involved in clopidogrel-induced gastric mucosal injury, acting through p38 MAPK activation.

Objective: To study the concentration level and characteristics of indoor particle matter ≤ 2.5 µm in aerodynamic diameter (PM2.5) under extreme weather condition., Methods: During the period of haze in January 2013 and the fireworks and firecracker setting off in the Spring Festival of February 2013, three monitoring sites located indoor and outdoor were respectively selected by Beijing CDC, considering the vertical and horizontal distance, windows tightness and human activity indoor. PM2.5 samples were collected by filters and measured by laboratory weight method. At the same time, the meteorological data was also collected., Results: The median (quartiles) of overall concentration level of indoor PM2.5 was 87.76 µg/m(3) (52.05-174.48 µg/m(3)) and was lower than that of outdoor PM2.5 (128.79 µg/m(3), 95.14-221.88 µg/m(3); Z = -4.13, P < 0.01). The concentration of three indoor monitoring sites was different (χ(2) = 23.09, P < 0.01). The PM2.5 concentrations of monitoring point B in poor sealing window was the highest (94.05 µg/m(3); 63.46-189.17 µg/m(3)) and point C in sealed and less human activity, which was the lowest (77.89 µg/m(3), 51.19-144.40 µg/m(3)). The concentration level of indoor PM2.5 in the haze period (273.22 µg/m(3), 223.44-308.47 µg/m(3)) was higher than the overall concentration level of indoor PM2.5 (Z = -5.20, P < 0.01). The concentration level of indoor PM2.5 in the fireworks and firecracker period (167.90 µg/m(3), 129.15-187.90 µg/m(3)) was higher than that in the Spring Festival period (7 days, 72.76 µg/m(3), 36.97-145.30 µg/m(3), Z = -2.34, P < 0.05) and the overall concentration level of indoor PM2.5 (Z = -1.98, P < 0.05); however, it was lower than the concentration level of indoor PM2.5 in the haze period (Z = -3.43, P < 0.01). The I/O ratio (indoor concentration/outdoor concentration) was all less than 1.00 except 4, which was between 1.00-1.09. The mean I/O ratio in monitoring site B, monitoring site A and monitoring site C was 0.69 ± 0.21, 0.64 ± 0.23 and 0.58 ± 0.18, respectively, show significant bias (F = 22.85, P < 0.01). During the period of haze, the fireworks and firecracker and fine weather (when ambient PM2.5 concentration was lower than the standard value of 75 µg/m(3)), the mean I/O ratio was 0.87 ± 0.14, 0.68 ± 0.08 and 0.51 ± 0.18, respectively, showing significant bias (F = 29.88, P < 0.05). Under conditions of snow and high wind speed ( ≥ 3.4 m/s), PM2.5 concentration decreased to the valley point. The valley value of I/O ratio only occurred after several days of high windy weather. Moreover, the PM2.5 concentration level of indoor air showed a delayed 1-2 days after the haze weakened or disappeared., Conclusion: Mass concentration of indoor PM2.5 increased significantly with increases of outdoor concentration. Haze and setting off fireworks/firecracker could lead to a serious decline of indoor air quality (IAQ), and the improvement of IAQ was lagging behind the outdoor changes.