ObjectiveTo investigate the effect of icaritin on the small cell lung cancer cell lines NCI-H446 and its mechanism. MethodsThe NCI-H446 cells at logarithmic growth phase were divided into control and icaritin groups. The cells in the control group were normally treated and cells in the icaritin group were incubated with icaritin (8 μmol/L). Thiazole blue and flow cytometry were used to examine the proliferation and apoptotic changes in the two groups 48 hours after incubation respectively. Gene expression of Janus kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3) were detected by real-time quantitative polymerase chain reaction. The changes of JAK2, STAT3, phospho-JAK2 (p-JAK2), phospho-STAT3 (p-STAT3), Bax and BCL-2 protein were detected by Western blotting. ResultsCompared with the control group, the proliferation rate of NCI-H446 cells in the icaritin group was significantly lower (P<0.05), but the apoptotic rate of NCI-H446 cells in the icaritin group was significantly higher (P<0.05). After the treatment with icaritin, the expression of JAK2 and STAT3 mRNA had no obvious differences. The Western blotting results showed that there was no significant changes in total JAK2, STAT3 protein (P>0.05), but an increasing trend in p-JAK2, p-STAT3 and Bax was observed with the decreasing of BCL-2 (P<0.05). ConclusionIcaritin can inhibit the proliferation and promote the apoptosis of NCI-H446 cells and the effect may be achieved through JAK2/STAT3 signal transduction pathway.
ObjectiveTo summary the advances of application of JAK/STAT signal transduction pathways in severe acute pancreatitis (SAP). MethodsBy using the method of literature review, the relevant literatures on JAK/STAT signal transduction pathway and its role in various organs damage of SAP were reviewed. ResultsIn the early of SAP, due to the pancreatic acinar cells were damaged, lead to the pancreatic enzyme release, then caused the local inflammatory mediators such as cytokines release, activated the JAK/STAT signal transduction pathways, and through the cascade effect with other signaling pathways further lead to the greater amounts of the release of inflammatory mediators, and that caused the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). ConclusionsThe JAK/STAT signal transduction pathway may be the key factor of cytokine waterfall cascade reaction process in SAP. Inhibition of this pathway may be a new measure to control the "inflammatory reaction waterfall" in treatment SAP.
Rheumatoid arthritis (RA) is a chronic autoimmune disease remarkably characterized by synovitis of joints, whose pathogenesis is complicated and not yet fully elucidated. A variety of cells, cytokines and intercellular signaling pathways are involved in the occurrence and development of RA. The mitogen activation protein kinase (MAPK) signaling pathway is closely related to the pathogenesis of RA, and plays an important role in the formation of pannus, synovitis, and bone destruction. This paper reviews the research progress of MAPK signaling pathway in RA from the aspects of the interaction of MAPK signaling pathway with a variety of key cells and cytokines in the pathogenesis of RA, in order to provide a direction and theoretical basis for anti-RA drug therapy research.
ObjectiveTo observe whether interleukin-27 (IL-27) intervention could diminish allergic airway inflammation of mouse asthma induced by ovalbumin (OVA) and to investigate the related molecular mechanisms. MethodsSixty female C57/6J mice were randomly divided into six groups, a control group, an asthma group, two IL-27 prevention groups and two IL-27 treatment groups. Based on being sensitized and challenged with OVA in the asthma model, two kinds of IL-27 intervention asthma models were set up, one of which was low-dose multiple prevention model, the other was high-dose few times treatment model. HE stain and inflammation score were done for the lungs. CD4+ T cells were purified from mice spleen and cultured under Th2 medium with/without IL-27. Interleukin-4 (IL-4) was measured by ELISA. CD4+ T cells were cultured under different stringent Th2 medium and stimulated by IL-27. The level of total signal transducer and activator of transcription-1 (STAT1) protein and phos-STAT1 were tested by Western blot. ResultsIn low-dose multiple prevention group, IL-27 inhibited inflammation around bronchial and vascular obviously, the inflammation score was lower than the asthma group (P < 0.05), while the treatment group had no obvious statistical significance (P > 0.05). IL-27 repressed Th2 differentiation of naïve CD4+ T cells which was independent of interferon-γand IL-10. This effect was via STAT1 signaling pathway. CD4+ T cells from asthma mice or cultured under high-IL-4 inducing medium were found impairment of STAT1 phosphorylation. ConclusionsIL-27 could inhibit Th2 differentiation of naïve CD4+ T cells, but not in already committed Th2-CD4+ T cells. The inhibition effect of IL-27 for airway inflammation is obvious in prevention group, while the treatment group shows obviously resistance to inhibitory effect of IL-27. Already committed Th2-CD4+ T cells existed in asthma airway might be the reason for IL-27 resistance.
Objective To review the latest development of the research on the selfrenwal signaling pathway and culture system in vitro of the embryonic stem cells(ESCs). Methods The recent articlesabout the selfrenewal signaling pathway and culture system in vitro of the ESCs were extensively reviewed. Results Understanding of the molecular mechanism of the selfrenewalin vitro and pluripotency of the ESCs was considered important for developing improved methods of deriving, culturing and differentiating these cells into the cells that could be successfully used in the clinical practice. Conclusion A further research is needed to elucidate the selfrenewal signaling pathway and the pluripotency of the ESCs and the culture systemin vitro forthe human ESCs remains to be further improved and developed.
Objective To introduce the basic research and cl inical potential of the hair foll icle stem cells related signal transduction in prol iferation and differentiation. Methods The recent original articles about the hair foll icle stem cells were extensively reviewed. Results Many different signal pathways had been involved in the skin development and self-newals.The hair foll icle stem cells could play an important role in the skin self-renewal and regeneration which were modulated by several different signal pathways, which included bone morphogenetic protein/transforming growth factor β, Wnt, Notch and ectodysplasin A genes. Conclusion The hair foll icle stem cells may be a future approach to repair cutaneous wounds as a cell therapy．
Objective To probe into the roles of inositol 1, 4, 5-trisphosphate (IP3) and bcl-2 gene expression in inhabiting hepatocellular carcinoma of nude mice by quercetin. Methods Animals with hepatocellular carcinoma in quercetin group were treated with injection peritoneum of quercetin 50 mg/（kg·d ） for 3 weeks, while which in control group were treated with 0.4% DMSO of RPMI 1640 0.05 ml/（g·d）. Then the volume and the weight of tumors were measured, IP3, bcl-2 mRNA and bcl-2 protein were assayed by IP3-［3H］ Birtrak Assay, RT-PCR and Western blot respectively. Results The volume and weight of tumors in quercetin group were lower than those in control group 〔（15.8±10.1） mm3 vs. （52.3±26.5） mm3 in volume, （44.8±10.4） mg vs.（91.3±31.4） mg in weight， P＜0.01〕. Content of IP3 in quercetin group was lower than that in control group 〔（13.4±1.4） pmol/mg prot vs. （35.3±6.6） pmol/mg prot， P＜0.01〕. There was no significant difference in bcl-2 mRNA expression between quercetin group and control group 〔RI （the gray degree multiply area of bcl-2 /the gray degree multiply area of β-actin）： 0.55±0.05 vs. 0.79±0.19， P＞0.05〕， but the expression of bcl-2 protein in quercetin group was lower than that in control group (RI: 1.07±0.12 vs. 6.69±1.80, P＜0.01). Conclusion Quercetin can inhabit the growth of hepatocellular carcinoma tansplanted into liver of nude mice by reducing IP3 production and down-regulating bcl-2 gene expression.
To summarize Notch, basic hel ix-loop-hel ix (bHLH) and Wnt gene signal transduction pathways in the process of differentiation and development of neural stem cells. Methods The l iterature on the gene signal transduction pathway in the process of differentiation and development of neural stem cells was searched and then summarized and analyzed. Results The formation of Nervous System resulted from common actions of multi-signal transduction pathways. There may exist a fixed threshold in the compl icated selective system among Notch, bHLH and Wnt gene signal transduction pathways. Conclusion At present, the specific gene signal transduction pathway of multi pl ication and differentiation of neural stem cells is still unclear.
ObjectiveTo investigate the associations of signal transducers and activators of transcription 6 (STAT6) gene polymorphisms with susceptibility to tuberculosis in western Chinese Han population.MethodsA total of 900 tuberculosis patients and 1 534 healthy controls of West China Hospital of Sichuan University were enrolled from January 2014 to February 2016. Improved multiplex ligation detection reaction method was used to detect four polymorphisms (rs1059513, rs73118432, rs841718, and rs10783813) of STAT6 gene. The allelic frequencies, genetic types, and different genetic models were analyzed using the chi-square test and unconditional logistic regression models to evaluate the associations of STAT6 gene with tuberculosis risk.ResultsEventually, a total of 856 cases and 1 511 health controls were recruited in our study. No significant differences were observed in allele frequencies, genotype distributions, or genetic models (additive model, dominant model and recessive model) at rs1059513, rs73118432, rs841718, and rs10783813 in STAT6 gene (P>0.05). We found a strong linkage disequilibrium among rs73118432, rs841718, and rs10783813, but there was no statistical difference in haplotype frequencies between the two groups (P>0.05).ConclusionsSTAT6 gene rs73118432, rs841718, rs10783813, and rs1059513 polymorphisms might have no associations with tuberculosis susceptibility in western Chinese Han population. Further studies with larger sample sizes are needed to comfirm these results.
Objective To explore the molecular mechanism of pathogenesis and signal pathway of platelet activation in acute respiratory distress syndrome (ARDS). Methods Thirty healthy Sprague-Dawley rats were randomly divided into 5 groups. Four groups were intravenously injected with oleic acid (OA, 0.25 ml/kg) to establish ARDS rat model. One group was intravenously injected with normal saline (NS) in same dose as control group. After injection of oleic acid for 2 h, 6 h, 24 h, 72 h in four OA groups, and injection of saline for 2 h in the control group, the rats were sacrificed. Blood was sampled from the abdominal aorta, then platelets were separated for abstracting platelet protein. The mitogen-activated protein kinase kinase 3 (MKK3) phosphorylation level in platelet was detected by Western blot method, to explore the changes of platelet mitogen activated protein kinase (MAPKs) signal transduction pathway in ARDS, and the relationship between the changes and the pathogenesis of ARDS. Results Platelet MKK3 phosphorylation level significantly increased 6-72 h after injection of oleic acid (P＜0.05). It was 2.4 times that of the control group in 6 h group (0.50±0.09vs. 0.21±0.05), peaked and 3.7 times that of the control group in 24 h group (0.78±0.06), then fell slightly but still significantly higher than the control group in 72 h group (0.75±0.13). Conclusion The activation process of platelets is related with MKK3-p38 MAPK signaling pathway in ARDS.