AIM: To explore the effect of deoxynivalenol on apoptosis and proliferation of mouse thymocytes in vivo. METHODS: Effect of deoxynivalenol at different concentrations on apoptosis and proliferation of mouse thymocytes in vivo were studied with animal experiment, electron microscopic observation, DNA agarose gel electrophoresis and flow cytometric analyses. RESULTS: FCM analysis showed that the apoptosis rates of the thymocytes in DON groups (0 5 mg/kg, 1 mg/kg, 2 mg/kg, 4 mg/kg and 8 mg/kg) were significantly higher than that in control ( P

Objective To investigate the relationship of STAT3 signal transduction pathway with proliferation,apoptosis and COX-2 expression of human esophageal carcinoma Eca-109 cell lines.Methods Eca-109 cells were treated with selective JAK2 inhibitor,AG490.MTT assay was used to detect the proliferation of Eca-109 cells,apoptosis was detected by flow cytometry,agarose gel electrophoresis of DNA and transmission electron micrograph(TEM).The expression of JAK2、p-JAK2、p-Stat3 and COX-2 was examined by Western blot.RT-PCR was performed to detect the levels of COX-2 mRNA expression.Results AG490 significantly inhibited the growth of human Eca-109 cells in a dose and time-dependent manner and induced apoptosis.AG490 inhibited the expressions of JAK2/STAT3 signal transduction pathway protein and down-regulated the expressions of p-JAK2 and p-Stat3(P

Objective To prepare a thermosensitive in situ gel system containing berberine hydrochloride for ocular use. Methods The in situ thermosensitive gel system of berberine hydrochloride was prepared by Poloxamer 407 (P407) and Poloxamer 188 (P188) as thermosensitive materials,the formulation was optimized by determining solution-gelation conversion temperature by using stirring method. The content of berberine hydrochloride was determined by HPLC. Results The gelation temperature of in situ thermosensitive gel containing berberine hydrochloride formulations lowered as the P407 concentration increased,as the P188 concentration increased gradually the gelation temperature initially increased to maximum and then decreased. The gelation temperature all increased after simulated tear fluid (STF) dilution. The fitted equation was established for the gelation temperature with the concentration of Poloxamer solutions after diluted by STF. An optimized formulation by Design-Expert software was freely flowing liquid at 29.7 ℃ and convert to a firm gel at 34.5 ℃ after STF diluted. Conclusion In situ thermosensitve gel system complies with the requirement for ophthalmic application and shows great potential in ocular application.

AIM: To explore the effects of riboflavin and ascorbic acid on the apoptosis induced by deoxynivalenol(DON) in mouse thymocytes. METHODS: The effects of riboflavin and ascorbic acid on the apoptosis and proliferation inhibition of thymocytes induced by DON in KM mice were studied with animal experiment, DNA agarose gel electrophoresis and flow cytometric DNA content analysis. RESULTS: Apoptosis rate of thymocytes in DON (4 mg/kg) treated group was 13 73%?1 53% The percentages of apoptosis in riboflavin (1 25 mg/kg-10 mg/kg) and ascorbic acid (25 mg/kg-100 mg/kg) pretreated thymocytes groups were significantly lower than that in DON group ( P

The critical time of avian leukosis virus subgroup J (ALV-J)-mediated immunosuppression was determined by body weight, relative immune organ weight, histopathology, and presence of group specific antigen and antibodies in specific pathogen-free (SPF) chickens. CD4+ and CD8+ cell activity in the spleen, total and differential leukocyte counts in blood, and viral RNA levels in spleen were measured. Significant growth suppression was observed in the two ALV-J-infected groups. A strong immune response by infected groups was present in spleen at 2-weeks-of-age, but after 4-weeks-of-age, the response decreased quickly. The thymus and bursa showed persistent immunosuppression until 4-weeks-of-age. Proliferation of fibroblasts and dendritic cells were observed in immune organs at 4- and 5-weeks-of-age. However, the granulocyte cell number was markedly lower in the infected groups than in the control group. In group 1 (day 1 infection) CD4+ cells increased during the second week but significantly decreased during the fourth week, while group 2 (day 7 infection) showed the opposite effect. Viral RNA increased significantly by the fourth week. These data identify 3~4 weeks post-infection as the key time at which the ALV-J virus exerts its immunosuppressive effects on the host.
Animals ; Antibodies, Viral/blood ; Antigens, CD4/blood ; Antigens, CD8/blood ; Avian Leukosis/*immunology/transmission/virology ; Avian leukosis virus/classification/*immunology ; Body Weight ; *Chickens ; China ; Enzyme-Linked Immunosorbent Assay/veterinary ; Immune Tolerance ; Leukocyte Count/veterinary ; Poultry Diseases/*immunology/transmission/virology ; RNA, Viral/genetics ; Real-Time Polymerase Chain Reaction/veterinary ; Reverse Transcriptase Polymerase Chain Reaction/veterinary ; Specific Pathogen-Free Organisms ; Spleen/immunology

Objective To determine the effect of rapamycin(Rapa) on JAK2, ABCA3, and the immune checkpoint PD-1/PD-L1 in exosomes derived from JAK2 V617F positive HEL cells. Methods Human erythroleukemia HEL cells (JAK2 V617F mutation-positive) were cultured in vitro, and rapamycin was added at concentrations of 10, 50, and 100 nmol/L. The control group was established and cell proliferation inhibition rate was detected by CCK-8. Based on the inhibition rate of cell proliferation, cells intervened with 10 and 50 nmol/L Rapa were selected. Exosomes were extracted using a kit and identified by Western blot and flow cytometry. JAK2, ABCA3, and PD-1/PD-L1 mRNA changes in exosomes were detected by fluorescent quantitative PCR. The expression of exosome PD-1/PD-L1 protein was determined by flow cytometry. Results The exosomes extracted with the exosome kit all expressed characteristic CD9, CD63, and CD81 proteins, which were consistent with the general characteristics of exosomes. JAK2 mRNA can be detected in exosomes from HEL cells; Rapa reduced exosome production by HEL cells, and dose-dependently decreased gene expression of JAK2, ABCA3, and PD-L1 in exosomes. In addition, Rapa inhibited exosomal PD-L1 protein expression and had no significant effect on PD-1 protein expression. Conclusion HEL cells may transmit JAK2 mutant gene signals via exosomes. Rapa can reduce the production of exosomes and inhibits JAK2 mutated signals delivered by exosomes and suppresses PD-L1 protein expression.

The incidence of hematologic malignancies is increasing, and although new drugs and treatments have made great progress, relapse and drug resistance are still urgent problems to be solved. Exosomes are tiny membrane vesicles secreted in cells that carry lipid bilayer membrane structures including mRNA, microRNA and proteins. It carries and transmits important signaling molecules, forming an entirely new intercellular information transfer system that exhibits a wide range of biological properties and functions in organisms. Tumor cell exosomes are confirmed to contribute to cancer cell proliferation, angiogenesis, invasiveness, distant metastasis and drug resistance. Multiple studies have shown that exosomes from some malignant hematological tumor cells are closely related to tumor resistance. This review summarizes the research progress of exosomes in the mechanism of drug resistance of hematologic malignancies, in order to provide a theoretical basis for the clinical treatment of hematologic malignancies.

OBJECTIVETo investigate the effects of triptolide on proliferation and regulation of ras-MAPKs pathway in human fibroblast-like synoviocytes of rheumatoid arthritis (RA-HFLS) treated with tumor necrosis factor (TNF-alpha).

METHODRA-HFLS were cultured with TNF-alpha in the presence or absence of variable doses of triptolide (0.28, 2.8, 28, 140 nmol x L(-1)) in vitro. Cell proliferation was evaluated by MTS assay. The phosphorylation status of Ras-MAPKs-associated proteins (Ras, p-P38, p-ERK and p-JNK) were detected by Western blot analysis.

RESULTTriptolide could obviously decrease the RA-HFLS viability in a dose-dependent manner and the inhibition ratio was 0.28%, 5.05%, 30.83% and 43.77% respectively. In addition, triptolide could also suppressed the expression of Ras, p-P38, p-ERK and p-JNK.

CONCLUSIONTriptolide has an notable inhibiting effect on proliferation of RA-HFLS and the molecule mechanism is due in part to the direct suppression of abnormal activation of Ras-MAPKs pathway.

Animals ; Cell Line ; Cell Proliferation ; drug effects ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Gene Expression Regulation ; drug effects ; MAP Kinase Signaling System ; drug effects ; Mice ; Mitogen-Activated Protein Kinases ; metabolism ; Phenanthrenes ; pharmacology ; Synovial Membrane ; cytology ; drug effects ; metabolism ; Tumor Necrosis Factor-alpha ; pharmacology ; ras Proteins ; metabolism

This review summarized the researches about physical activity levels, measurement methods, influencing factors and interventions for children and adolescents with intellectual disability. The physical activity levels of children and adolescents with intellectual disability were low, and their health status was not optimistic. The joint efforts of individuals, families and the society were needed to improve their levels of physical activity. The effectiveness of existing physical activity intervention methods should be further discussed. Therefore, focusing on the health demands of children and adolescents with intellectual disability, more researches are needed about in-depth analysis of the dose-effect relationship between physical activity and health indicators, and exploring of effective intervention for physical activity in the future.

Objective     To analyze the risk factors of atrial fibrillation (AF) after radical esophagectomy, providing the basis for prevention and treatment of AF after radical esophagectomy. Methods     We conducted a retrospective analysis of 335 patients' clinical data, who accepted laparoscopic combined thoracic or open radical esophagectomy in the same treatment group at Department of Thoracic Surgery of Shengjing Hospital of China Medical University between January 2014 and August 2016. There were 262 males and 73 females at age of 65.1 (43-78) years. Results     There were 48 of 335 patients with AF within 1 week after surgery. By univariate analysis: age, gender, history of peripheral vascular disease and cardiac stents or angina pectoris, preoperative brain natriuretic peptide (BNP), preoperative left ventricular diastolic dysfunction, operation pattern, intraoperative blood transfusion and lymph nodes and pericardial adhesion were possible risk factors. By multivariate analysis: age, gender, history of cardiac stents or angina pectoris, preoperative BNP, operation pattern, intraoperative blood transfusion and lymph nodes and pericardial adhesion were risk factors. Conclusion     The risk factors of AF after radical esophagectomy are age, gender, history of cardiac stents or angina pectoris, preoperative BNP, operation pattern, intraoperative blood transfusion and lymph nodes and pericardial adhesion. Perioperative positive intervention to above factors may reduce the incidence of postoperative AF.