Overexpression of DCF1 Inhibits Glioma through Destruction of Mitochondria and Activation of Apoptosis Pathway

Gliomas are the most common brain tumors affecting the central nervous system and are associated with a high mortality rate. DCF1 is a membrane protein that was previously found to play a role in neural stem cell differentiation. In the present study, we found that overexpression of dcf1 significantly inhibited cell proliferation, migration, and invasion and dramatically promoted apoptosis in the glioblastoma U251 cell line. DCF1 deletion mutations in the functional region showed that the complete structure of DCF1 was necessary for apoptosis. Furthermore, significantly lower tumorigenicity was observed in athymic nude mice by transplanting U251 cells overexpressing dcf1. To decode the apoptosis induced by dcf1, mitochondrial structure and membrane potential in glioma cells were investigated and the results indicated obvious mitochondrial swelling, destruction of cristae, and a significant decline in membrane potential. Mechanismly, caspase-3 signaling was activated. Finally, endogenous dcf1 silence in U251 cells was investigated. Results showed a highly methylation at -1339 and -1322 position at dcf1 promoter sequence, revealing the causal relationship between dcf1 gene and tumorigencicity. The present study identified a previously unknown cancer apoptosis mechanism involving dcf1 overexpression and provided a novel approach to potentially treat glioma patients

Revisiting membrane rejection: On the relationship between solute size and pore size in the nanofiltration regime

The molecular resolution of nanofiltration depends on resistance to solute transport along the permeation channel, manifesting steric hindrance and hydrodynamic friction. To date there is little direct experimental evidence of reporting on rejection in nanofiltration for ideal membranes with uniform pores, and defined size solutes. However the recent availability of defined nanoparticles in the range 1-20 nm makes new investigations feasible. Phenomenological models for predicting solute permeation through defined cylindrical channels started with the Hagen-Poiseuille equation, which includes viscosity as the key parameter for solvent permeation. The Bowen-Welfoot model was developed to incorporate several correction terms to account for solute-pore interaction. However, the Bowen-Welfoot model generates ideal rejection curves only under the conditions of low pressure-driven flow. Under high-pressure conditions, the rejection curve as predicted by Bowen-Welfoot model assumes a broad spread, similar to the rejection profile predicted by Ferry’s sieving model, demonstrating steric hindrance based on solute-pore interaction as the key parameter in rejection. We set out to obtain new fundamental experimental evidence to interrogate these nanofiltration models. In this work, transport of spherical nanoparticle (NP) imaging probes through model polycarbonate track etch (PCTE) and alumina (Al) membranes were studied empirically using citrate-coated gold nanoparticles of defined sizes (1, 5, 15 nm) and straight channel PCTE (nominal pore diameters 10 and 30 nm) and Al (nominal pore diameters 40 nm) membranes with uniform pore sizes. A priori calculations of theoretical rejections of the membranes with respect to different solute sizes were computed using Bowen-Welfoot pore-flow model. Two simulation approaches were used to describe both discrete and continuous (Gaussian distribution) pore size distributions using probability density functions and taking into account the solvent viscosity as a function of pore radii. Empirically measured rejections of nanoparticle imaging probes were compared with simulation results to confirm the phenomena of hindered transport of NPs inside defined cylindrical nanochannels. Given the experimentally observed evidence of hindered transport of solute moving through pores of commensurate dimensions, we revisited the measurement of rejection in nanofiltration regime in different operational modes: dead-end filtration, diafiltration and cross-flow using a same combination of nanoparticle solute size and membrane pore size. Our results show that dead-end and cross-flow measurements of rejection values do not always agree well with each other; while our diafiltration experiments provide evidence of solutes getting trapped inside membrane pores of commensurate sizes (permanent loss) or solutes in retarded movement through the pores due to much faster solvent flow (transient accumulation). In summary, this fundamental study will illustrate the relation between solute sizes and pore sizes, the implications of it on measurements of rejection values, and the applications of the use of nanoparticle imaging agents for quantifying pathway dimensions in commercial membranes such as reverse osmosis thin film composites and integrally skinned asymmetric nanofiltration membranes with tortuous pore channels that are otherwise difficult to imaging the sizes directly using electron micrographic techniques

Antimikrobna rezistencija i svojstva virulencije bakterije Enterococcus faecium izolirane u goveda s kliničkim mastitisom iz pokrajine Ningxia, Kina

This study was conducted to determine the antimicrobial resistance and virulence traits of 32 Enterococcus faecium isolates from clinical bovine mastitis cases in Ningxia Province, China. In total, 32 E. faecium isolates were taken from subclinical bovine mastitis on the basis of morphological characterization and biochemical testing, and screened for antimicrobial susceptibility. The virulence genes of the isolates were studied using polymerase chain reaction (PCR). The disc diffusion assay revealed a high occurrence of resistance against tetracycline (78.1%) and erythromycin (68.8%) in the E. faecium isolates. However, all tested E. faecium were susceptible to linezolid and vancomycin. Moreover, all E. faecium isolates harbored the erythromycin-resistant genes ermA, ermB and ermC, as well as the tetracycline-resistant genes tetK, tetL and tetM. Furthermore, all E. faecium isolates carried more than 3 of the tested virulence genes. The presence of agg (100%), cpd (100%), efaA (100%), gelE (93.4%), and esp (75.0%) was found most frequently in all the tested isolates. These findings are useful for making appropriate antimicrobial choices and developing antivirulence therapies for subclinical bovine mastitis caused by E. faecium in Ningxia Province, China.Istraživanje je provedeno kako bi se odredila antimikrobina rezistencija i svojstva virulencije izolata bakterije Enterococcus faecium uzetih u goveda s kliničkim mastitisom. U ukupno 32 izolata goveda iz pokrajine Ningxia u Kini, procijenjena je antimikrobna osjetljivost na temelju morfološke karakterizacije i biokemijskih pretraga. Geni virulencije izolata istraženi su polimeraznom lančanom reakcijom (PCR). Disk-difuzijski test je u izolatu bakterije E. faecium pokazao visoku pojavnost rezistencije na tetraciklin (78,1 %) i eritromicin (68,8 %). Svi su pretraženi izolati bili osjetljivi na linezolid i vankomicin i imali gene rezisentne na eritromicin ermA, ermB i ermC, kao i na tetraciklin, tetK, tetL i tetM. Osim toga svi izolati E. faecium nosili su više od tri istraživana gena virulencije. Najčešći geni bili agg (100 %), cpd (100 %), efaA (100 %), gelE (93,4 %) i esp (75,0 %). Ovi rezultati mogu u pokrajini Ningxia u Kini pridonijeti pravilnom izboru antimikrobnog lijeka i razvoju uspješne terapije za supklinički goveđi mastitis uzrokovan bakterijom E. faecium

Whole exome sequencing and system biology analysis support the "two-hit" mechanism in the onset of Ameloblastoma

Ameloblastoma is the most frequent odontogenic tumor. Various evidence has highlighted the role of somatic mutations, including recurrent mutation BRAF V600E, in the tumorigenesis of Ameloblastoma, but the intact genetic pathology remains unknown. We sequenced the whole exome of both tumor tissue and healthy bone tissue from four mandibular ameloblastoma patients. The identified somatic mutations were integrated into Weighted Gene Co-expression Network Analysis on publicly available expression data of odontoblast, ameloblast, and Ameloblastoma. We identified a total of 70 rare and severe somatic mutations. We found BRAF V600E on all four patients, supporting previous discovery. HSAP4 was also hit by two missense mutations on two different patients. By applying Weighted Gene Co-expression Network Analysis on expression data of odontoblast, ameloblast, and Ameloblastoma, we found a proliferation-associated gene module that was significantly disrupted in tumor tissues. Each patient carried at least two rare, severe somatic mutations affecting genes within this module, including HSPA4, GNAS, CLTC, NES, and KMT2D. All these mutations had a ratio of variant-support reads lower than BRAF V600E, indicating that they occurred later than BRAF V600E. We suggest that a severe somatic mutation on the gene network of cell proliferation other than BRAF V600E, namely second hit, may contribute to the tumorigenesis of Ameloblastoma

The Empirical Study on the Relations among Network Structure, Strategic Flexibility and Technology Innovation Performance

Nowadays, enterprise has to learn to make Technology Innovation by making full use of resources from other organizations or agencies because of the increasing of scientific and technological level and economic globalization. Through studying on the related articles about Network Structure, Strategic Flexibility and Technology Innovation Performance, this paper proposes a conceptual model which can explain the relationship between Network Structure, Strategic Flexibility and Technology Innovation Performance. By using SPSS 16.0 to analyse the sample data which is acquired from distributing questionnaires, expert visiting and others, this paper examines the affecting degree empirically of Network Structure, Strategic Flexibility on Technology Innovation Performance. Thus, enterprise should perfect enterprise’s network structure, enhance enterprise Strategic Flexibility and then improve the Technology Innovation Performance. Key words: Technology innovation performance; Network structure; Strategic flexibility; Empirical stud

Serum from patients with ankylosing spondylitis can increase PPARD, fra-1, MMP7, OPG and RANKL expression in MG63 cells

OBJECTIVES: To explore the effects of serum from patients with ankylosing spondylitis on the canonical Wnt/β-catenin pathway and to assess whether the serum has an osteogenic effect in MG63 cells. METHODS: MG63 cells were cultured with serum from 45 ankylosing spondylitis patients, 30 healthy controls, or 45 rheumatoid arthritis patients. The relative PPARD, fra-1, MMP7, OPG and RANKL mRNA levels were measured using quantitative real-time polymerase chain reaction. Associations between gene expression and patient demographics and clinical assessments were then analyzed. RESULTS: MG63 cells treated with serum from ankylosing spondylitis patients had higher PPARD, fra-1, MMP7 and OPG gene expression than did cells treated with serum from controls or rheumatoid arthritis patients (all

Non-volatile Components and Filamentary Morphology of Fresh Leaves of Zigui Simian Tea

To investigate the characteristics of quality formation of Simian tea, the non-volatile components, mineral elements and filamentary structure of fresh leaves from different positions of ‘Simian Tucha’ tea plants, endemic to Zigui, were analyzed using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), inductively coupled plasma optical emission spectrometry (ICP-OES), and scanning electron microscopy (SEM). The results showed that the non-volatile components were more abundant in the leaves with higher tenderness, with amino acids, alkaloids, catechins, and aroma glycosides being mainly concentrated in the first (L1) and second leaves (L2). Theanine, organic acids, and flavonoids were mainly concentrated in the third leaf (L3), while the content of non-volatile components in the older leaves was relatively lower. The accumulation of mineral elements greatly varied among tea leaves with different tenderness. The contents of nitrogen, phosphorus, potassium, zinc, and copper in L1 (32.41 mg/g, 4.53 mg/g, 15.65 mg/g, 45.45 μg/g, and 10.75 μg/g, respectively) and L2 (30.60 mg/g, 3.70 mg/g, 14.12 mg/g, 35.82 μg/g, 9.02 μg/g, respectively) were higher than those in older leaves. The contents of iron, manganese, and calcium were higher in mature leaves. Through SEM observation, it was found that the filamentary structure of Simian tea leaves consisted of two forms, triple-stranded coil and single-stranded coil, and was distributed in the internal thread or ringed vessels of the xylem in the vascular bundles in the midvein and lateral veins, and the number of filamentary structures was higher in the second, third and fourth leaves than that in buds and L1

Preparation, purification, and identification of novel antioxidant peptides derived from Gracilariopsis lemaneiformis protein hydrolysates

Gracilariopsis lemaneiformis (G. lemaneiformis) protein was hydrolyzed with alkaline protease to obtain antioxidant peptides. The enzymatic hydrolysis conditions were optimized through single-factor and orthogonal experiments. The results showed that the optimal process parameters were using 2% of alkaline protease, and substrate concentration of 1 g/100 mL and hydrolyzed 2 h at pH 8.0. Gel filtration chromatography and RP-HPLC were adopted for isolating and purifying the antioxidant peptides from the G. lemaneiformis protein hydrolysate (GLPH). Three novel antioxidant peptides were identified as LSPGEL (614.68 Da), VYFDR (698.76 Da), and PGPTY (533.57 Da) by nano-HPLC-MS/MS. The results of ABTS free radical scavenging rate demonstrated PGPTY exhibited the best antioxidant activity (IC50 = 0.24 mg/mL). Moreover, LSPGEL, VYFDR, and PGPTY were docked with Keap1, respectively. The molecular docking results suggested PGPTY had smaller docking energy and inhibition constants than the other two peptides. Finally, the cell viability assay evidenced the protective effect exerted by the antioxidant peptide on H2O2-induced oxidative damage. Above findings showed the potential of using antioxidant peptides from GLPH as antioxidants

Age-Related Loss of Innate Immune Antimicrobial Function of Dermal Fat Is Mediated by Transforming Growth Factor Beta

Dermal immature adipocytes fightagainstStaphylococcusaureusinfectionby secreting antimicrobial peptidesduring adipogenesis. Zhang et al.demonstrate that activation of the TGF-bpathway suppresses the adipogenicpotential of dermal fibroblasts andtherefore leads to an age-dependent lossof antimicrobial protection fromdermal fat. 皮下脂肪细胞作为皮肤的最后一道防线，有很重要的免疫抗菌功能，分化中脂肪细胞释放大量抗菌肽，这是一种人自源抗生素，能有效地抑制细菌生长。但这一重要的宿主天然免疫功能在发育和老化过程中如何被调控还不为人知。研究人员发现，老化过程中皮肤脂肪丢失是和真皮成纤维细胞（dermal fibroblasts）失去脂肪分化能力密切相关的。真皮成纤维细胞是皮肤深处的特化细胞，可以产生结缔组织并帮助皮肤从损伤中恢复。【Abstract】Dermal fibroblasts (dFBs) resist infection by locallydifferentiating into adipocytes and producing cathe-licidin antimicrobial peptide in response toStaphylo-coccusaureus(S.aureus). Here, we show thatneonatal skin was enriched with adipogenic dFBsand immature dermal fat that highly expressed cath-elicidin. The pool of adipogenic and antimicrobialdFBs declined after birth, leading to an age-depen-dent loss of dermal fat and a decrease in adipogene-sis and cathelidicin production in response to infec-tion. Transforming growth factor beta (TGF-b),which acted on uncommitted embryonic and adultdFBs and inhibited their adipogenic and antimicro-bial function, was identified as a key upstream regu-lator of this process. Furthermore, inhibition of theTGF-breceptor restored the adipogenic and antimi-crobial function of dFBs in culture and increasedresistance of adult mice toS.aureusinfection. Theseresults provide insight into changes that occur in theskin innate immune system between the perinataland adult periods of life.This work was supported by NIH grant R01-AR069653 to L.Z. and R.L.G. and NIH grants R01-AI083358, R01-AR052728, and U19-AI117673 to R.L.G. M.V.P. is supported by a Pew Charitable Trust grant, NIH grants U01-AR073159 and R01-AR067273, National Science Foundation (NSF) grant DMS1763272, and Simons Foundation grant 594598 (to Qing Nie). C.F.G.J. is supported by NSF-GRFP grant DGE-1321846 and MBRS-IMSD training grant GM055246. Y.Z. is supported by NIH grant R01-AI107027. 该项目研究得到了厦门大学双一流启动基金的支持