ABSTRACT
Hypoxia is beneficial for the differentiation of stem cells transplanted for myocardial injury, but mechanisms underlying this benefit remain unsolved. Here, we report the impact of hypoxia-induced Jagged1 expression in cardiomyocytes (CMs) for driving the differentiation of cardiac stem cells (CSCs). Forced hypoxia-inducible factor 1 (HIF-1) expression and physical hypoxia (5% O) treatment could induce Jagged1 expression in neonatal rat CMs. Pharmacological inhibition of HIF-1 by YC-1 attenuated hypoxia-promoted Jagged1 expression in CMs. An ERK inhibitor (PD98059), but not inhibitors of JNK (SP600125), Notch (DAPT), NF-B (PTDC), JAK (AG490), or STAT3 (Stattic) suppressed hypoxia-induced Jagged1 protein expression in CMs. c-Kit CSCs isolated from neonatal rat hearts using a magnetic-activated cell sorting method expressed GATA4, SM22 or vWF, but not Nkx2.5 and cTnI. Moreover, 87.3% of freshly isolated CSCs displayed Notch1 receptor expression. Direct co-culture of CMs with BrdU-labeled CSCs enhanced CSCs differentiation, as evidenced by an increased number of BrdU/Nkx2.5 cells, while intermittent hypoxia for 21 days promoted co-culture-triggered differentiation of CSCs into CM-like cells. Notably, YC-1 and DAPT attenuated hypoxia-induced differentiation. Our results suggest that hypoxia induces Jagged1 expression in CMs primarily through ERK signaling, and facilitates early cardiac lineage differentiation of CSCs in CM/CSC co-cultures HIF-1/Jagged1/Notch signaling.
ABSTRACT
Acute myeloid leukemia (AML) is the most common type of leukemia at present. Although clinical treatment has a certain effect on this disease, most patients still die of relapse or its treatment related diseases. Nowadays, chimeric antigen receptor (CAR) T cells therapy technology has developed rapidly, and has become a hot topic in tumor immunotherapy. The high expression of CD123 in AML cells, low expression or non expression in normal hematopoietic stem cells and tissues, make more and more researchers focus on the technology of CD123+cell immunotherapy. Some studies have confirmed that CD123 CAR-T cells have a certain effect on AML, which provides a new way for clinical treatment of relapsed or refractory AML. This review summarizes the structure, production and delivery methods of CD123 CAR-T cells, and the current research status and shortcomings of CD123 CAR-T cells.
ABSTRACT
AIM: To explore the expression and significance of receptor tyrosine kinase anexelekto (Axl) in nasopharyngeal carcinoma (NPC).METHODS: Immunohistochemistry was used to detect the Axl protein expression of 78 patients with NPC and 32 patients with nasopharyngeal chronic inflammation (NPI).The correlations between the Axl protein levels and the clinical parameters of NPC patients were analyzed.NPC cells were cultured in vitro, and the expression of Axl in well differentiated CNE1 cells, poorly-differentiated CNE2Z cells and undifferentiated C666-1 cells was detected by immunofluorescence staining.After treatment of the CNE1and C666-1 cells with Axl specific inhibitor TP-0903, CCK-8 assay was used to detect cell viability, flow cytometry was adopted to analyze the cell cycle distribution, qPCR was used to examine the mRNA levels of Axl and proliferating cell nuclear antigen (PCNA), and Western blot was used to examine the protein expression of Axl and p-Axl.RESULTS: Axl protein was localized in the cell membrane and cytoplasm.The rate of high expression of Axl in NPC was significantly higher than that in NPI (P<0.01).High Axl expression showed no correlations with NPC patients'' age, gender and M stage, while positively correlated with the clinical stage, T stage and N stage (P<0.05).Axl protein showed a low level in the CNE1 cells, but showed a high level in CNE2Z and C666-1 cells.TP-0903 inhibited cell viability in concentration and time dependent manners.TP-0903 at 2 nmol/L showed significant inhibitory effects, as evidenced by arresting the cell cycle at G0 phase and reducing Axl activity and PCNA expression.CONCLUSION: High expression of Axl promotes the clinical progress of NPC.TP-0903 significantly inhibits the viability of NPC cells, suggesting that Axl may be a valuable target in the NPC treatment.
ABSTRACT
Objective To investigate the clinical efficacy of ilaprazole and bismuth combined ten-day standard quadruple therapy and sequential therapy in the treatment of patients with Helicobacter pylori (H .pylori)infected chronic gastritis.Methods A total of 200 patients with H .pylori-positive chronic gastritis diagnosed by gastroendoscopy examination and rapid urease test (RUT)were randomly divided into standard quadruple therapy group and sequential therapy group,100 cases in each group.One group received ilaprazole,bismuth,amoxicillin-clavulanatepotassium and ofloxacin 10-day standard quadruple therapy, and the other group received ilaprazole, amoxicillin-clavulanatepotassium, ofloxacin and furazolidone 10-day sequential therapy.In four to six weeks after the therapy,the condition of H .pylori eradication was detected by a 14 C-urea breath test.The improvement of clinical symptoms and adverse effects were also observed. Normal distributed and variance homogenized measurement data were compared by t test,while unordered categorical data were analyzed by chi-square test and the exact probability method,and categorical data were compared by two independent sample rank sum test.Results The per-protocol analysis values of H .pylori eradication rates of the standard quadruple therapy group and the sequential therapy group were 88.54%(85/96)and 87.23%(82/94),respectively,while the intention-to-treat analysis values were 85 .00%(85/100)and 82.00%(82/100 ),respectively.The effective rates of symptomatic relief of upper abdominal pain,acid regurgitation,heart burning in the standard quadruple therapy group and the sequential therapy group were 95 .83%(92/96)and 95 .74%(90/94),respectively. The incidence of adverse effects which weve very mild was 6.25 % (6/96 ) and 7.44% (7/94 ), respectively.There was no statistically significant difference in the above three factors between the two groups (all P >0.05).Conclusions Ilaprazole and bismuth combined 10-day standard quadruple therapy and sequential therapy in the treatment of patients with H .pylori positive chronic gastritis both achieves high rates of H .pylori eradication and symptom relief with mild adverse effects.