Effects of bilateral repetitive transcranial magnetic stimulation on prospective memory in patients with schizophrenia: A double-blind randomized controlled clinical trial.

AIMS: To investigate effects of repetitive transcranial magnetic stimulation (rTMS) on the prospective memory (PM) in patients with schizophrenia (SCZ). METHODS: Fifty of 71 patients completed this double-blind placebo-controlled randomized trial and compared with 18 healthy controls' (HCs) PM outcomes. Bilateral 20 Hz rTMS to the dorsolateral prefrontal cortex at 90% RMT administered 5 weekdays for 4 weeks for a total of 20 treatments. The Positive and Negative Symptom Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), and PM test were assessed before and after treatment. RESULTS: Both Event-based PM (EBPM) and Time-based PM (TBPM) scores at baseline were significantly lower in patients with SCZ than that in HCs. After rTMS treatments, the scores of EBPM in patients with SCZ was significantly improved and had no differences from that in HCs, while the scores of TBPM did not improved. The negative symptom scores on PANSS and the scores of almost all subscales and total scores of SANS were significantly improved in both groups. CONCLUSIONS: Our findings indicated that bilateral high-frequency rTMS treatment can alleviate EBPM but not TBPM in patients with SCZ, as well as improve the negative symptoms. SIGNIFICANCE: Our results provide one therapeutic option for PM in patients with SCZ.

[Research Progress on the Role of Chromatin Remodeling Factor BRG1 in Acute Myeloid Leukemia].

BRG1 (Brahma-related gene 1, BRG1) is the ATPase subunit of SWI/SNF chromatin remodeling complexes, which plays an important role in cell cycle regulation, DNA repair and tumor development. Unlike the evidence as tumor suppressor genes in the past reports, latest researches show that BRG1 plays an important role in sustaining the growth of leukemia cells in acute myeloid leukemia, and these effects on normal hematopoietic stem cells are dispensable. Further studies of the role and mechanism of BRG1 in acute myeloid leukemia will contribute to the development of a new and promising targeted therapy strategy. This article reviews the role of BRG1 on leukemia cells and leukemia stem cells in AML and discusses the related mechanism, which providing some reference for the targeted treatment strategy of AML.

Clonal dissemination of KPC-2 producing Klebsiella pneumoniae ST11 clone with high prevalence of oqxAB and rmtB in a tertiary hospital in China: results from a 3-year period.

BACKGROUND: Carbapenemase-producing Klebsiella pneumoniae (CPKP) strains have emerged as a major problem for healthcare systems. The aim of this study was to determine the circulating clones and analyze the clinical and molecular characteristics of CPKP in our hospital. METHODS: A total of 74 carbapenemase producers collected from our hospital from 2012 to 2014 were analyzed for the prevalence of extended-spectrum ß-lactamase (ESBLs), plasmid-mediated quinolone resistance genes (PMQRs), exogenously acquired 16S rRNA methyltransferase (16S-RMTase), and plasmid-mediated AmpC enzyme (pAmpCs) by PCR and DNA sequencing. The sequence types (STs) of the carbapenemase producers were analyzed by multi-locus sequence typing (MLST). And Pulsed-field gel electrophoresis (PFGE) was performed to investigate the genetic relationship of KPC-2 producing strains. Clinical data were retrieved from the medical records. RESULTS: KPC-2 (n = 72) was the predominant enzyme followed by NDM-1 (n = 2); The genes blaCTX-M, blaSHV, blaTEM-1, blaDHA-1, rmtB, armA, oqxA, oqxB, and qnrB were present in 29 (39.2 %), 27 (36.5 %), 46 (62.2 %), 2 (2.7 %), 25 (33.8 %), 1 (1.4 %), 60 (81.1 %) and 56 (75.7 %), 6 (8.1 %) isolates, respectively. MLST analysis revealed 10 different STs. The most dominant ST was ST11 (78.4 %, 58/74), followed by ST15 (8.1 %, 6/74). PFGE patterns of the KPC-2 producing K. pneumoniae isolates exhibited clonal dissemination of ST11 and ST15 clones as well as a genetic diversity of the remaining strains. CONCLUSION: The intra- and inter-hospital cross-transmission of KPC-2-producing K. pneumoniae ST11 co-carrying oqxAB and rmtB in our hospital strongly suggested that rapid identification of colonized or infected patients and screening of carriers is quite necessary to prevent a scenario of endemicity.

Methylation status of the FHIT gene in the transformed human mesenchymal F6 stem cell line.

The fragile histidine triad (FHIT) gene is known to be a tumor suppressor gene and the abnormal methylation of FHIT has been identified in leukemia and several solid tumors. The transformation of the tumor F6 cell line from human fetal mesenchymal stem cells (FMSCs) was first reported in a previous study that also identified the presence of a population of cancer stem cells in the F6 cell line. However, the existence of the epigenetic changes during the transformation process have yet to be elucidated. To confirm the role of the FHIT gene in the transformation process of FMSC, the expression level and methylation status of the FHIT gene was examined in F6 tumor cells and FMSCs. Additionally, the alteration in cell morphology, the cell cycle and apoptosis in F6 cells following 5-Aza-CdR treatment was assessed. It was found that the FHIT gene was expressed in FMSCs, but not in F6 cells. The methylation-specific PCR results demonstrated that the promoter methylation of FHIT genes existed in the F6 cell line. Subsequent to treatment with 5-Aza-CdR the expression of FHIT genes was restored in F6 cells. In addition, the morphology of F6 cells was altered, and the cell cycle was arrested in the G2 phase, with the initiation of apoptosis. Overall, the present findings demonstrated that the FHIT gene was methylated in F6 cells and demethylation treatment lead to changes in the biological characteristics, thereby promoting the apoptosis of F6 cells. FHIT gene methylation may be one of the molecular events involved in the development and transformation of FMSCs into F6 tumor cells.

Erythropoietin attenuates hypertrophy of neonatal rat cardiac myocytes induced by angiotensin-II in vitro.

OBJECTIVE: Erythropoietin (EPO) is a haematopoietic hormone that has been confirmed as a novel cardioprotective agent. In this study, we test the hypothesis that EPO inhibits angiotensin-II (Ang-II)-induced hypertrophy in cultured neonatal rat cardiomyocytes. MATERIAL AND METHODS: Cultured neonatal rat cardiomyocytes were used to evaluate the effects of EPO on Ang-II-induced hypertrophy in vitro. The surface area and mRNA expression of atrial natriuretic (ANF) myocytes were employed to detect cardiac hypertrophy. A phosphatidylinositol 3'-kinase (PI3K) inhibitor LY294002 and an endothelial nitric oxide synthase (eNOS) inhibitor L-NAME were also employed to detect the underlying mechanism of EPO. Intracellular signal molecules, such as Akt (PKB), phosphorylated Akt, eNOS and transforming growth factor-beta1 (TGF-beta1) protein expression were determined by Western blot. Nitric oxide (NO) levels in the supernatant of cultured cardiomyocytes were assayed using an NO assay kit. RESULTS: The results indicate that EPO significantly attenuates Ang-II-induced hypertrophy shown as inhibition of increases in cell surface area and ANF mRNA levels. NO production was also increased proportionally in the EPO-treated group. EPO enhanced Akt activation and eNOS protein expression, whereas LY294002 or L-NAME partially abolished the anti-hypertrophic effect of EPO, accompanied by a decrease in Akt activation, eNOS protein expression and/or a reduction of NO production. EPO also down-regulated the protein expression of TGF-beta1. CONCLUSION: We conclude that EPO attenuates cardiac hypertrophy via activation of the PI3K-Akt-eNOS-NO pathway and the down-regulation of TGF-beta1.

Oct4, a novel marker for human gastric cancer.

BACKGROUND AND OBJECTIVE: Octamer-4 (Oct4), a transcription factor involved in regulating human embryonic stem cells (ESCs), may play a role in tumorigenesis. Since little is known about the efficacy of Oct4 as a potential biomarker for gastric cancer (GC), we investigated its expression in GC tissues and its relationship to various clinicopathological parameters. METHODS: Primary tumor tissues and matching, adjacent non-cancerous tissues were obtained from 62 GC patients, and Oct4 expression was examined by reverse transcription-PCR (RT-PCR) and real-time PCR. Twenty biopsy specimens of atrophic gastritis and gastric ulcer individually were collected as control. To detect Oct4 expression in the paired GC and non-cancerous tissues at the protein level, Western blotting and immunohistochemistry (IHC) were employed. Correlation analyses were conducted to assess the relationship between Oct4 expression and clinicopathological parameters. RESULTS: Oct4 expression levels were higher in GC tissues compared to matching, adjacent non-cancerous tissues, atrophic gastritis and gastric ulcer tissues. Additionally, Oct4 expression in GC tumors correlated with their differentiation status, but not with patient age or gender, tumor size, TNM stage, depth of invasion, or the presence of lymph node metastasis. CONCLUSIONS: Oct4 may be a potential biomarker for the initiation, progression, and differentiation of human GC.

[Erythropoietin suppresses the expressions of TGF-beta1 and collagen in rat cardiac fibroblasts induced by angiotensin II].

OBJECTIVE: Recent studies have shown cardiac protection effects of erythropoietin (EPO). The present experiment was designed to investigate the effects of EPO on TGF-beta1, nitric oxide synthase (NOS), collagen contents induced by angiotensin II (Ang II) in rat cardiac fibroblasts (CFs) and explore the roles of PI3-K/Akt signaling pathway on related effects. METHODS: Neonatal rat CFs was isolated by collagenase and trypsinase digestion methods. PBS, EPO, Ang II in the absence or presence of LY294002, an inhibitor of PI3-K, or L-NAME, an inhibitor of NOS, were added to CFs and cultured for 24 hours. The concentration of collagen I and collagen III in culture medium were quantitated by ELISA. The levels of nitric oxide (NO) and the activities of NOS as well as NOS isoforms were measured by chemical enzymic method. Western blot was applied to detecting the protein expressions of Akt, p-Akt, eNOS, iNOS, and TGF-beta1. RESULTS: The concentrations of collagen I and collagen III in CFs culture medium were significantly increased while the level of NO was significantly decreased by Ang II and these changes were significantly suppressed by EPO in a dose dependent manner. The effects of EPO on eNOS and NO could be blocked by LY294002. L-NAME could block EPO's effect on NO but not on the eNOS expression. The suppression effects on expressions of TGF-beta1 and collagen by Ang II in CFs were blocked by both LY294002 and L-NAME. CONCLUSION: EPO suppresses the upregulated expressions of TGF-beta1 and increased production of collagen induced by Ang II through activating the PI3-K/Akt signaling pathway in neonatal rat CFs.