Loss of GATA4 C-Terminus by p.S335X Mutation Modulates Coronary Artery Vascular Smooth Muscle Cell Phenotype.

Coronary artery disease (CAD) has been the leading cause of morbidity and mortality worldwide, and its pathogenesis is closely related with the proliferation and migration of vascular smooth muscle cell (VSMC). We previously reported a truncated GATA4 protein lacking C-terminus induced by p.S335X mutation in cardiomyocyte from ventricular septal defect (VSD) patients. However, it is still unclear whether GATA4 p.S335X mutation could influence the development of CAD. GATA4 wild-type (WT) and p.S335X mutant (MU) overexpression plasmids were constructed and transfected transiently into rat coronary artery smooth muscle cell (RCSMC) to observe the proliferative and migratory abilities by MTS and wound healing assay, respectively. PCR array was used to preliminarily detect the expression of phenotypic modulation-related genes, and QRT-PCR was then carried out to verify the screened differentially expressed genes (DEGs). The results showed that, when stimulated by fetal bovine serum (10%) for 24 h or tumor necrosis factor-α (10 or 30 ng/ml) for 10 or 24 h, deletion of GATA4 C-terminus by p.S335X mutation in GATA4 enhanced the proliferation of RCSMC, without alteration of the migration capability. Twelve DEGs, including Fas, Hbegf, Itga5, Aimp1, Cxcl1, Il15, Il2rg, Il7, Tnfsf10, Il1r1, Irak1, and Tlr3, were screened and identified as phenotypic modulation-related genes. Our data might be beneficial for further exploration regarding the mechanisms of GATA4 p.S335X mutation on the phenotypic modulation of coronary VSMC.

Functional maturation of immature ß cells: A roadblock for stem cell therapy for type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease caused by the specific destruction of pancreatic islet ß cells and is characterized as the absolute insufficiency of insulin secretion. Current insulin replacement therapy supplies insulin in a non-physiological way and is associated with devastating complications. Experimental islet transplantation therapy has been proven to restore glucose homeostasis in people with severe T1DM. However, it is restricted by many factors such as severe shortage of donor sources, progressive loss of donor cells, high cost, etc. As pluripotent stem cells have the potential to give rise to all cells including islet ß cells in the body, stem cell therapy for diabetes has attracted great attention in the academic community and the general public. Transplantation of islet ß-like cells differentiated from human pluripotent stem cells (hPSCs) has the potential to be an excellent alternative to islet transplantation. In stem cell therapy, obtaining ß cells with complete insulin secretion in vitro is crucial. However, after much research, it has been found that the ß-like cells obtained by in vitro differentiation still have many defects, including lack of adult-type glucose stimulated insulin secretion, and multi-hormonal secretion, suggesting that in vitro culture does not allows for obtaining fully mature ß-like cells for transplantation. A large number of studies have found that many transcription factors play important roles in the process of transforming immature to mature human islet ß cells. Furthermore, PDX1, NKX6.1, SOX9, NGN3, PAX4, etc., are important in inducing hPSC differentiation in vitro. The absent or deficient expression of any of these key factors may lead to the islet development defect in vivo and the failure of stem cells to differentiate into genuine functional ß-like cells in vitro. This article reviews ß cell maturation in vivo and in vitro and the vital roles of key molecules in this process, in order to explore the current problems in stem cell therapy for diabetes.

The prognostic significance of POD24 in 106 cases with splenic marginal lymphoma with bone marrow invasion / 中华血液学杂志

Objective: To explore the effect of progression of disease within 24 months (POD24) on overall survival (OS) of splenic marginal lymphoma (SMZL) with bone marrow invasion, and to compare the clinical characteristics between POD24 SMZL with non-POD24 SMZL patients. Methods: The SMZL patients with bone marrow invasions were retrospectively analyzed between January 2002 and January 2017 treated in our institute, and the patients with sufficient follow-up time to judge POD24 were evaluated the clinical characteristics and prognosis, patients who died of non-progressive factors were excluded. Results: 106 patients were enrolled with a median age of 57 (25-79) years old. ①Clinical characteristics: All patients presented with bone marrow invasion and splenomegaly, 59.4% (63/106) with huge spleen, 14.8% (15/101) with hepatomegaly. Complex karyotype were found in 22.7% (18/79) patients; 13q deletion, 11q (ATM) deletion, 17p (TP53) deletion, and CEP12 abnormality patients presented with the percentage of 5.1% (4/78) , 1.3% (1/72) , 2.5% (2/80) , and 7.5% (4/53) , respectively.②Survival analysis: Univariate analysis showed that POD24, HGB less than 100 g/L and FISH detection of trisomy 12 were poor prognostic factors of OS. Multivariate analysis showed that only POD24 had independent prognostic significance[HR=20.116 (95%CI 2.226-181.820) , P=0.008]. ③Subgroup features: Patients with POD24 had significantly higher rates of mediastinal lymphadenopathy (63.6%vs 18.9%, P=0.005) and complex karyotype (50.0%vs 17.9%, P=0.024) than those without POD24. While the incidence of abdominal lymphadenopathy, anemia, thrombocytopenia, the lower albumin, and the increasing lactate dehydrogenase were higher in POD24 patients, but with no statistically difference. Conclusion: POD24 is an independent prognostic factor of the OS in SMZL. SMZL patients with mediastinal lymphadenopathy and complex karyotypes when diagnosed have a higher risk of POD24.

Chemical profiling of Jinqi Jiangtang tablets by HPLC-ESI-Q-TOF/MS / 中国天然药物

AIM@#To profile the chemical constituents in Jinqi Jiangtang tablets.@*METHOD@#Based on the chromatographic retention behavior, fragmentation patterns of chemical components, and published literatures, a high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-Q-TOF/MS) method was established to characterize and identify components in Jinqi Jiangtang tablets.@*RESULTS@#A total of 52 chemical compounds, including eight iridoid glycosides, seven phenolic acids, twelve alkaloids, six flavonoids, and nineteen saponins, were identified in Jinqi Jiangtang tablets.@*CONCLUSION@#The established method could serve as a powerful tool for structural characterization and quality control of this Chinese herbal preparation.