Elevated expression of CDT1 in childhood acute lymphoblastic leukemia promotes cell proliferation, invasion and migration through activation of EMT.

Acute lymphoblastic leukemia (ALL) is a malignant disease of the hematopoietic system. At present, the mechanism and pathogenesis of ALL have not been fully clarified. This study aimed to illustrate the roles of Cdc10 protein-dependent transcript 1 (CDT1) in ALL. Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) was performed to examine serum levels of CDT1 in childhood ALL patients and healthy volunteers. The interaction between CDT1 expression and prognosis of childhood ALL was analyzed. Meanwhile, expressions of CDT1 in ALL cell lines were determined. Furthermore, CDT1 knockdown model was constructed in ALL cells, and Cell Counting Kit-8 (CCK-8), and Transwell assays were conducted to analyze the effect of CDT1 on the biological functions of ALL cells. Potential mechanism was further explored through detecting the expressions of Epithelial-to-mesenchymal transition (EMT)-related genes. RT-qPCR results indicated that serum level of CDT1 in childhood ALL patients was remarkably higher than that of healthy volunteers. Childhood ALL patients with high expression of CDT1 had lower overall survival rate compared with those expressing low expression of CDT1. CDT1 knockdown remarkably decreased the proliferation and metastasis abilities of pediatric ALL cells. Results of western blot showed that CDT1 might contribute to the malignant progression of childhood ALL via activating EMT. The findings showed that elevated CDT1 facilitated ALL metastasis by promoting EMT, suggesting that CDT1 played a pivotal role in ALL metastasis and may serve as a novel prognostic biomarker and therapeutic target.

Nanoconfinement effects of chemically reduced graphene oxide nanoribbons on poly(vinyl chloride).

Polymeric nanocomposites with graphene-based nanocarbons (GNCs) have been extensively studied with emphasis on the percolation of nanofillers toward electrical, rheological, and mechanical reinforcement. In this study, we report an unusual indirect reinforcing phenomenon of highly defective GNCs dispersed in the poly(vinyl chloride) (PVC) matrix via densification of the polymer packing originating from nanoscale confinement. Herein, chemically reduced graphene oxide nanoribbons (C-rGONRs) are employed as a nanofiller. The inclusion of defective and oxygen-functionalized C-rGONRs resulted in a dramatic densification of the PVC host with extremely low C-rGONR loading, largely exceeding the theoretical calculation from a rule of mixture. Along with the densification, the glass transition temperature of PVC also increased by 28.6 °C at 0.1 wt% filler loading. Remarkably, the oxygen barrier property and mechanical toughness under tension for the PVC/C-rGONR nanocomposite were the maximum when the greatest densification occurred. The structure-property relationship of the nanocomposites has been discussed with an emphasis on the nanoscale confinement phenomenon.

The importance of dermoscopy for the diagnosis of acquired bilateral telangiectatic macules: the angioid streak pattern reveals underlying chronic liver disease.

BACKGROUND: Acquired bilateral telangiectatic macules (ABTM) are a newly recognized disease entity, which manifest as multiple telangiectatic pigmented macules confined mostly to the upper arms. OBJECTIVES: To evaluate clinical and dermoscopic features in a group of 50 patients with ABTM and to determine the diagnostic usefulness of dermoscopy in ABTM. METHODS: Patients were selected from two tertiary teaching hospitals in Korea [Pusan National University Hospitals (Busan and Yangsan)]. Fifty patients (41 males and 9 females; mean age 48.1 years; range 26-78 years) with ABTM were included in the study. The dermoscopic findings were graded using a 4-point scale: none (0), mild (1), moderate (2) and severe (3). In addition, the results of 23 patients with and 27 patients without chronic liver disease (CLD) were compared to determine whether the presence of CLD affects dermoscopic findings. RESULTS: Three distinct dermoscopic patterns were observed; brown pigmentations, telangiectasia (linear-irregular vessels) and an angioid streak pattern. Brown pigmentation in the group without CLD had higher severity score than those in CLD group (mean score: 2.00 vs. 1.48, P = 0.033). However, mean telangiectasia severity score was higher in the CLD group (2.14 vs. 1.39, P < 0.001). The angioid streak pattern was more severe and more common in patients with CLD than in those without [1.37 vs. 0.35 (P < 0.001) and 63.0% vs. 26.1%, respectively]. CONCLUSIONS: Detailed observations with dermoscopy can provide first clues of the presence of ABTM and underlying chronic liver disease.

Preoperative evaluation and surgical technique of functional and cosmetic aspects in zygomatic complex fracture patients.

The zygomatico-maxillary complex functions as the principle buttress of the face and is the cornerstone to an individual’s aesthetic appearance. Its fracture not only creates cosmetic deformities owing to its position and facial contour, but can also cause disruption of ocular and mandibular functions. The aim of this study was to evaluate the quality, efficacy and impact of internal fixation of zygomatic complex fractures on functional and cosmetic outcomes. A prospective study was carried out on 100 patients who were divided according to the classification and the severity of injury. Subjective evaluation was submitted based on the patient’s perception of signs and symptoms in the preoperative and postoperative periods. Intraoperative and postoperative assessment of bone reduction quality was made according to the type of the fracture and related difficulties; also, the difference between these groups was observed as functional and esthetic outcome. To optimize the treatment of zygomatic bone fractures, a pre-designed questionnaire was used for subjective evaluation of symptoms and treatment outcome. In 70% of cases, ophthalmologic consultation was taken and was most common in type VII fractures (100% cases). Neurosensory disturbance was the most common finding (60%), followed by diplopia (56R%), pain upon mouth opening (54%) and malar depression (50%). Out of all possible 400 fracture sites in 100 patients of zygomatic complex fractures, 266 (66.5%) fractures were detected by clinical examination, in contrast to 330 (82.5%) on radiological examination, which were highest at zygomatic-maxillary buttress (93%) followed by infraorbital rim (91%) and almost equal among fronto-zygomatic site (72%) and zygomatic arch (74%). The scores from the questionnaire for annoyance were significantly higher for paraesthesia (23%) than for trismus (10%), pain (8.5%), or deformity (8.25%). Residual deformity and pain significantly influenced the total satisfaction. Conclusively, there are many treatment modalities available for zygomatic complex fractures, and the preferred methods should be selected on the basis of fracture type, fracture severity, pre-operative signs and symptoms. Regarding the requirements of fracture site exposure and actual fixation, one priority should be to minimize postoperative complications, morbidity and residual deformities.

[Clinical analysis of nose rhabdomyosarcoma].

Objective:To improve the diagnosis of the nose rhabdomyosarcoma.Method:Twenty-four patients with nose rhabdomyosarcoma were studied retrospectively.Result:Among 24 patients with nose rhabdomyosarcoma, three patients were in stage Ⅰ, four patients were in stage Ⅱ, eleven patients were in stage Ⅲ, and six patients were in stage Ⅳ. Embryonal rhabdomyosarcoma is the commonest in all the pathological types. Most patients need comprehensive therapy, including surgery operation, radiotherapy, and multicycle chemotherapy. Prognosis was poor in most of the cases. The survival rate of one year was 70.8% (17/24), and survival rate of three years was 30.3% (8/24).Conclusion:Different surgical protocols should be adopted for different patients, and postoperative chemoradiotherapy should be adopted for advanced treatment. By means of multidisciplinary collaboration, the patient's survival time would be prolonged.

FOXA1 acts upstream of GATA2 and AR in hormonal regulation of gene expression.

Hormonal regulation of gene expression by androgen receptor (AR) is tightly controlled by many transcriptional cofactors, including pioneer factors FOXA1 and GATA2, which, however, exhibit distinct expression patterns and functional roles in prostate cancer. Here, we examined how FOXA1, GATA2 and AR crosstalk and regulate hormone-dependent gene expression in prostate cancer cells. Chromatin immunoprecipitation sequencing analysis revealed that FOXA1 reprograms both AR and GATA2 cistrome by preferably recruiting them to FKHD-containing genomic sites. By contrast, GATA2 is unable to shift AR or FOXA1 to GATA motifs. Rather, GATA2 co-occupancy enhances AR and FOXA1 binding to nearby ARE and FKHD sites, respectively. Similarly, AR increases, but not reprograms, GATA2 and FOXA1 cistromes. Concordantly, GATA2 and AR strongly enhance the transcriptional program of each other, whereas FOXA1 regulates GATA2- and AR-mediated gene expression in a context-dependent manner due to its reprogramming effects. Taken together, our data delineated for the first time the distinct mechanisms by which GATA2 and FOXA1 regulate AR cistrome and suggest that FOXA1 acts upstream of GATA2 and AR in determining hormone-dependent gene expression in prostate cancer.

Microporous carbon nanosheets with redox-active heteroatoms for pseudocapacitive charge storage.

We report microporous carbon nanosheets containing numerous redox active heteroatoms fabricated from exfoliated waste coffee grounds by simple heating with KOH for pseudocapacitive charge storage. We found that various heteroatom combinations in carbonaceous materials can be a redox host for lithium ion storage. The bio-inspired nanomaterials had unique characteristics, showing superior electrochemical performances as cathode for asymmetric pseudocapacitors.

CCN3/NOV gene expression in human prostate cancer is directly suppressed by the androgen receptor.

Androgen receptor (AR) has essential roles during prostate cancer progression. With genome-wide AR-binding sites mapped to high resolution, studies have recently reported AR as a transcriptional repressor. How AR inhibits gene expression and how this contributes to prostate cancer, however, are incompletely understood. Through meta-analysis of microarray data, here we nominate nephroblastoma overexpressed (NOV) as a top androgen-repressed gene. We show that NOV is directly suppressed by androgen through the AR. AR occupies the NOV enhancer and communicates with the NOV promoter through DNA looping. AR activation recruits the polycomb group protein EZH2, which subsequently catalyzes histone H3 lysine 27 tri-methylation around the NOV promoter, thus leading to repressive chromatin remodeling and epigenetic silencing. Concordantly, AR and EZH2 inhibition synergistically restored NOV expression. NOV is downregulated in human prostate cancer wherein AR and EZH2 are upregulated. Functionally, NOV inhibits prostate cancer cell growth in vitro and in vivo. NOV reconstitution reverses androgen-induced cell growth and NOV knockdown drives androgen-independent cell growth. In addition, NOV expression is restored by hormone-deprivation therapies in mice and prostate cancer patients. Therefore, using NOV as a model gene we gained further understanding of the mechanisms underlying AR-mediated transcriptional repression. Our findings establish a tumor-suppressive role of NOV in prostate cancer and suggest that one important, but previously underestimated, manner by which AR contributes to prostate cancer progression is through inhibition of key tumor-suppressor genes.

TMPRSS2-ERG gene fusions induce prostate tumorigenesis by modulating microRNA miR-200c.

Chromosomal translocations that juxtapose the androgen-sensitive transmembrane protease, serine 2 (TMPRSS2) gene promoter to the oncogenic ETS-family transcription factor ERG result in excessive ERG overexpression in approximately 50% of prostate cancer (PCa) patients. Although numerous studies have investigated ERG-downstream genes, such studies have not attempted to examine miRNAs, which however are emerging to be important regulators of cancer. Through bioinformatics analysis of ChIP-Seq ERG data and miRNA expression profiling data we nominated miR-200c as a direct target of ERG. Experimentation of PCa cells with ERG overexpression or knockdown demonstrated that ERG directly repressed miR-200c expression by physically binding to the erythroblast transformation-specific (ETS) motif within its promoter. Consequently, miR-200c was downregulated in ERG-positive PCa, and miR-200c target gene expression was restored. In addition, the expression pattern of miR-200c target genes predicted ERG status in clinical PCa specimens. Furthermore, miR-200c was found to be important in modulating ZEB1 upregulation by ERG. Most importantly, miR-200c reconstitution fully reversed ERG-induced epithelial-to-mesenchymal transition (EMT), cell migration and invasion. Therefore, our study report miR-200c as the first miRNA target of ERG and a critical inhibitor of PCa cell motility. Therapeutic delivery of miR-200c may provide personalized treatment for patients with the molecular subtype of PCa that harbors TMPRSS2-ERG gene fusions.

Identification of nitrogen-fixing Paenibacillus from different plant rhizospheres and a novel nifH gene detected in the P. stellifer.

A total of 534 isolates were selectively obtained from different plant rhizospheres based on their growth on nitrogen-free medium and their resistance to 80 degrees C for 15 min. Of the 534 isolates, 23 isolates had nifH gene and exhibited nitrogenase activities. Based on 16S rDNA sequence, G + C content assay and DNA-DNA hybridization, by the 23 isolates, which were divided into four monophyletic clusters, all belonged to the Paenibacillus genus. NifH gene deduced amino acid alignment analysis revealed that cluster I, including 15 isolates, showed the highest NifH identity with Paenibacillus genus; while cluster II identified as P stellifer by DNA-DNA hybridization was consistent with four uncultured bacterial clones. This study suggested that the nitrogen-fixing Paenibacillus were distributed in various ecosystems and prevalent in different plant rhizospheres. It was the first demonstration that nitrogen fixation existed in P. jamilae and P. stellifer. In eight isolates identified as P. stellfer species, a novel nifH gene was detected in Paenibacillus.

Synergistic effect in treatment of C.I. Acid Red 2 by electrocoagulation and electrooxidation.

An aqueous C.I. Acid Red 2 solution was decolorized by electrolysis using iron as anode. The decolorization mechanism was investigated through experimental observations on the electrochemical behavior of C.I. Acid Red 2 on Pt rotating disk electrode, UV-visible spectra of the solution and IR spectra of the coagulated mixtures. It is found that the decolorization efficiency is high, over 98.0% after 40 min, and this high decolorization efficiency can be ascribed to the synergistic effect of electrocoagulation and electrooxidation. The electrocoagulation results from the electrogenerated iron hydroxide and the electrooxidation results from electrogenerated ferric ions. The results obtained from IR spectra shows that the decolorization of C.I. Acid Red 2 by electrooxidation is due to the partial or complete cleavage of C-N bonds in C.I. Acid Red 2.

Carboxylic acid functionalized multi-walled carbon nanotube-adsorption onto poly(methyl methacrylate) microspheres.

We prepared multi-walled carbon nanotube (MWNT) coated polymeric microspheres i.e., carboxylic acid functionalized MWNT (c-MWNT) adsorbed onto poly(methyl methacrylate) (PMMA) microspheres. Initially, the MWNT was functionalized with carboxylic acid functional group and PMMA microspheres were synthesized via a dispersion polymerization method separately. The c-MWNT/PMMA microspheres were then fabricated by blending technique i.e., simple mixing of c-MWNT and PMMA microspheres dispersed solutions under ultrasonication. Surface morphologies of the c-MWNT-adsorbed PMMA microspheres were observed using scanning electron microscopy (SEM). In addition, c-MWNT/PMMA microsphere suspension dispersed in silicone oil showed typical electrorheological characteristics of fibril structure under an applied electric field.

Heteropolymorphism of mitochondrial NADH dehydrogenase subunit 3 gene for the population analysis of chum salmon, Oncorhynchus keta.

Mitochondrial DNAs (mtDNAs) has been frequently used as genetic markers for the population genetic studies. In this study we used chum salmon (Oncorhynchus keta) from Korea, Japan andAmerica, and compared their mitochondrial NADH dehydrogenase subunit 3 (ND3) genes by DNA sequence analysis. Sequence variation was studied in the ND3 among total 11 individuals from three populations. The ND3 gene was amplified by PCR targeting parts of cytochrome oxidase III gene (COIII) and NADH dehydrogenase subunit 4L gene (ND4L). ND3 gene sequence, encoded 752 bps, presented some genetic variation in the chum salmon populations. The observed nucleotide variations inferred the distinct genetic differentiation of American salmons from Korean and Japanese chum salmons. Six sites of single nucleotide polymorphism (SNP) were explored in the ND3 locus. Denaturing gradient gel electrophoresis analysis also showed a clear heterogenous band in American salmons compared to Asian salmons.

Production of a polyclonal anti-myostatin antibody and the effects of in ovo administration of the antibody on posthatch broiler growth and muscle mass.

In this study, we produced a polyclonal antibody against unprocessed chicken myostatin and examined the effect of in ovo administration of the antibody on posthatch chicken growth and muscle mass. A PCR-amplified unprocessed chicken myostatin cDNA was cloned into an Escherichia coli expression vector, and myostatin proteins were expressed. Recombinant myostatin purified by electro-elution of the SDS-PAGE fractionated myostatin band was used as an immunogen to produce rabbit polyclonal antimyostatin antibody (pAb-AVM46). In Western blot analysis, the pAb-AVM46 showed high affinity to the myostatin propeptide, but little affinity to the mature myostatin. Two experiments examined the effect of in ovo administration of the pAb-AVM46 on posthatch chicken growth and skeletal muscle mass. In experiment 1, broilers from eggs injected once with 35 microg of the antibody into the yolk on d 3 of incubation had significantly lower combined thigh and leg weight at 4 wk posthatch than the controls that received no injection, or the broilers from eggs received the same dose of antibody into the albumen. In experiment 2, 2 different doses of the antibody (9 or 70 microg) were injected into the yolk, and the effects on body and muscle weight were examined at 5 wk posthatch. Birds from eggs injected with 70 microg of the antibody had significantly lighter (11.6%) combined thigh and leg weight than the control birds. The percentage of the combined thigh and leg weight to BW of the 70-microg group was also significantly lower than that of the control group (20.95 vs. 23.08%). The results of this study indicate that unprocessed full-length myostatin as an immunogen produced antibody populations having affinity mostly to the propeptide with little to the mature form. The decreased muscle weight observed in broilers injected with the antibody in the yolk indicates that myostatin activity was probably elevated by the binding of the antibody to the propeptide, and provides evidence that myostatin propeptide inhibits the biological activity of myostatin in broilers.

Production of a monoclonal anti-myostatin antibody and the effects of in ovo administration of the antibody on posthatch broiler growth and muscle mass.

Myostatin, a member of the transforming growth factor-beta (TGF-beta) superfamily, is a potent negative regulator of skeletal muscle growth. The objective of this study was to produce a monoclonal anti-myostatin antibody and to examine the effects of in ovo administration of the antibody on posthatch broiler growth and muscle mass. The mature form of myostatin was expressed in Escherichia coli and used as an immunogen in producing a monoclonal antibody against myostatin. One hybridoma clone (mAb-c134) that showed the strongest affinity to the immunogen in Western blot analysis was used in producing a large quantity of monoclonal anti-myostatin antibody. In Western blot analysis, this antibody showed a strong binding affinity to commercially available mature myostatin and demonstrated a certain level of cross-reactivity with recombinant human BMP2 but not with recombinant human TGF-beta3 or porcine TGF-beta1. Competitive ELISA demonstrated binding of the antibody to the native form of mature myostatin in solution. To examine the effects of in ovo administration of the mAb-c134 antibody, eggs were injected once with 40 microg of mAb-c134 in 50 mL of PBS either into the albumen or yolk on d 3 of incubation. Controls received no injection. After hatching, chicks were raised for 35 d. Broilers from eggs that had the antibody injected into the yolk had significantly heavier body (4.2%) and muscle (5.5%) mass than the controls in both male and female birds. In contrast, no significant effects on body and muscle mass were observed when the mAb-c134 antibody was injected into the albumen. The results of this study suggest that immunoneutralization of myostatin during embryonic development is a potential means to improve growth potential of broilers.

Three-dimensional quantitative structure activity relationship (3D-QSAR) analysis for in vitro toxicity of chlorophenols to HepG2 cells.

In the present paper, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were applied to investigate two 3D-QSAR models for the cytotoxicity of chlorophenols. These models have evaluated the intensity of chlorophenols' toxicity on HepG2 cells in vitro. The CoMFA model has both high consistency and predictability. The contribution of the electrostatic field to biological activity is greater than that of the steric field. The CoMSIA model used in this study includes two fields, one is hydrophobic field, and the other is electrostatic field. The relative contribution of them is 0.789:0.211. Consisted with the CoMFA model, the CoMSIA electrostatic filed also plays a dominant role. The CoMFA and CoMSIA contour maps significantly elucidated that the electrostatic field is more important than the other fields and might be one of the reasons resulting in potential reactive mechanism involved in cell proliferation inhibition.