OBJECTIVETo reveal the role of Phosphatidylinositol 3-kinases (PI3Ks) in regulating human diploid fibroblast (2BS cell) senescence as well as the possible mechanisms involved.

METHODSUsing a PI3Ks specific inhibitor, LY294002, cell cycle, apoptosis, proliferation, senescence association beta-galactosidase staining as well as senescence association CKIs, p16(INK4) and p21(Cip1) protein expressions were all measured in the low passages of 2BS cells.

RESULTSBoth 25 micro mol/L and 50 micro mol/L concentrations of LY294002 could cause a significant decrease in cells entering into S phase, and this cell cycle of G(1) phase arrest was dose-dependent. Meanwhile, LY294002 contributed to apoptosis, caused 2BS cell growth arrest, and activated senescence association beta-galactosidase (P < 0.05). In addition, LY294002 could induce time-course expressions of p16(INK4) and p21(Cip1) in 2BS cell lines.

CONCLUSIONSPI3Ks inhibitor LY294002 could induce senescence-like changes in 2BS cell lines. Two senescence associated CKIs, p16(INK4) and p21(Cip1), might be involved in this senescence phenotype proceeding in 2BS cell lines.

Cells, Cultured ; Cellular Senescence ; drug effects ; Chromones ; pharmacology ; Cyclin-Dependent Kinase Inhibitor p16 ; analysis ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins ; analysis ; Dose-Response Relationship, Drug ; Enzyme Inhibitors ; pharmacology ; Fibroblasts ; drug effects ; physiology ; G1 Phase ; drug effects ; Humans ; Morpholines ; pharmacology ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors

Objective:To investigate the understanding and application of the knowledge of premature infants in pediatricians participating in the Second Chinese Preterm Infant Academic Conference through questionnaires, and to carry out targeted continuing education for pediatricians in order to better guide the clinical diagnosis and treatment of grassroots pediatricians.Methods:The research was conducted in the form of a questionnaire survey.The survey objects were pediatricians participating in the " Second Chinese Preterm Infant Academic Conference" , and the results of the questionnaire were summarized and analyzed.The questionnaires were designed based on personal education background, employment time, current status of neonatal specialty in the hospital where they were, and knowledge of premature infant nutrition.Results:A total of 554 valid questionnaires were received.Among the pediatricians surveyed, 37.2% had a master's degree or higher; 344(62.1%) pediatricians came from Grade Ⅲ class A hospitals.According to the geographical distribution, age, education, working years, hospital level, hospital nature, annual delivery of obstetrics in hospitals, the number of beds in neonatal specialty wards, and the number of beds in NICU, the respondents were grouped, and the current status of premature births in China and the situation of using the growth curve(Fenton2013) of premature infants in work were compared.It was found that the proportion of those who used the Fenton curve of the 2013 version in Grade Ⅲ class A hospitals was higher than that in Grade Ⅲ class B hospitals and Grade Ⅱ hospitals(χ 2=47.663, P<0.05). The ratio was higher among women and children's health centers and general hospitals(χ 2=8.072, P<0.05). Conclusion:The academic annual conference for the purpose of continuing education, set up a pre-conference questionnaire for the participants during the preparation period, and set the content of the annual conference according to the needs of the target population, which can better solve the clinical problems of primary doctors and promote the improvement of primary doctors' diagnosis and treatment.

Hepatitis B virus (HBV) is the prototype of hepatotropic DNA viruses (hepadnaviruses) infecting a wide range of human and non-human hosts. Previous studies with duck hepatitis B virus (DHBV) identified duck carboxypeptidase D (dCPD) as a host specific binding partner for full-length large envelope protein, and p120 as a binding partner for several truncated versions of the large envelope protein. p120 is the P protein of duck glycine decarboxylase (dGLDC) with restricted expression in DHBV infectible tissues. Several lines of evidence suggest the importance of dCPD, and especially p120, in productive DHBV infection, although neither dCPD nor p120 cDNA could confer susceptibility to DHBV infection in any cell line. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a binding partner for the N-terminus of HBV large envelope protein. Importantly, knock down and reconstitution experiments unequivocally demonstrated that NTCP is both necessary and sufficient for in vitro infection by HBV and hepatitis delta virus (HDV), an RNA virus using HBV envelope proteins for its transmission. What remains unclear is whether NTCP is the major HBV receptor in vivo. The fact that some HBV patients are homozygous with an NTCP mutation known to abolish its receptor function suggests the existence of NTCP-independent pathways of HBV entry. Also, NTCP very likely mediates just one step of the HBV entry process, with additional co-factors for productive HBV infection still to be discovered. NTCP offers a novel therapeutic target for the control of chronic HBV infection.
Animals ; Carboxypeptidases/genetics/*metabolism ; Gene Products, pol/genetics/metabolism ; Heparan Sulfate Proteoglycans/metabolism ; Hepatitis B virus/*physiology ; Hepatocytes/metabolism/virology ; Organic Anion Transporters, Sodium-Dependent/antagonists & inhibitors/genetics/metabolism ; RNA Interference ; Symporters/antagonists & inhibitors/genetics/metabolism ; Viral Envelope Proteins/metabolism ; Virus Internalization

BACKGROUNDThe expressive level of glucose-regulated protein 78 (GRP78) is elevated and correlated with resistance of chemotherapy drugs in breast cancer cell. However, little is known about the relationship between its expression and drug resistance in non-small cell lung cancer (NSCLC). The aim of this study was to explore the relationship between drug resistance and the expression of GRP78 in NSCLC.

METHODSDrug sensitivity test was used to detect the resistance to 8 chemotherapy drugs in 52 NSCLC fresh surgical samples by methylthiazoletrazolium (MTT), and expression of GRP78 was detected by immunohistochemistry method. Spearman correlation assay was used to investigate the correlation between the GRP78 expression and drug resistance.

RESULTSThe resistance rates to paclitaxel (PTX), adriamycin (ADM), carboplatin (CBP), topotecan (TPT), navelbine (NVB), vincristine (VCR), cisplatin (DDP) and etoposide (VP-16) of the 52 samples were 42.31%, 57.69%, 63.46%, 65.38%, 67.31%, 73.08%, 78.85%, 90.38%, respectively. Fourteen cases showed the complete resistance to the total 8 chemotherapy drugs. Furthermore, the expression of GRP78 was stronger in poorly differentiated cancer as compared with the well and moderately differentiated cancer (P < 0.05), so as in stage II and III cancer than in stage I cancer (P < 0.05). Spearman correlation assay showed that there was a correlation between the chemotherapeutics resistance to ADM, VP-16, VCR, TPT and the expression of GRP78 in NSCLC (P < 0.05).

CONCLUSIONSIt is feasible to detect the drug sensitivity to chemotherapy for tumor cells by MTT method. The results of chemosensitivity assay in vitro are indicative of clinical drug administration in NSCLC. The detection of GRP78 isalso indicative of the resistance to chemotherapy drugs and the differentiation and the clinical stage in NSCLC.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective To explore the influencing factors of hyperlipidemia in 18-80 years old in Ningxia by structural equation model, and to analyze the direct and indirect effects of influencing factors of hyperlipidemia, so as to provide a basis for the formulation of prevention and treatment measures. Methods A total of 925 patients with hyperlipidemia from a chronic disease survey in 4 counties of Ningxia in April 2017 were selected as the case group (n=925), and residents without hyperlipidemia matched by sex and age were selected as the control group (n=925). A self-designed questionnaire was used to investigate the two groups of subjects. SPSS 22.0 software was used to conduct single factor T or Z test or χ² test for the possible influencing factors of hyperlipidemia, and Amos22.0 was used to construct structural equation model. Results The structural equation model showed that physiological condition had the greatest effect on hyperlipidemia, and the standardized regression coefficient was -0.351. The second was the monitoring of three key blood indicators (three-high indicators), and the total effect value was 0.082, while personal condition and dietary status had no direct influence on the prevalence of hyperlipidemia. Conclusion Physiological status is the most important factor affecting the prevalence of hyperlipidemia in 18 ~ 80 years old in Ningxia, followed by the monitoring of the three-high indicators. In the future, residents should be encouraged to strengthen health management, especially people with overweight, high uric acid, high blood glucose and hypertension, to control the level of blood lipids and reduce the incidence of hyperlipidemia.