Epigenetic gene regulation linked to oncogenic pathways is an important focus of cancer research. KDM3A, a histone H3 lysine 9 (H3K9) demethylase, is known to have a pro-tumorigenic function. Here, ...we showed that KDM3A contributes to liver tumor formation through the phosphatidylinositol 3-kinase (PI3K) pathway, which is often activated in hepatocellular carcinoma. Loss of Kdm3a attenuated tumor formation in Pik3ca transgenic (Tg) mouse livers. Transcriptome analysis of pre-cancerous liver tissues revealed that the expression of activator protein 1 (AP-1) target genes was induced by PI3K activation, but blunted upon Kdm3a ablation. Particularly, the expression of Cd44, a liver cancer stem marker, was regulated by AP-1 in a Kdm3a-dependent manner. We identified Cd44-positive hepatocytes with epithelial-mesenchymal transition-related expression profiles in the Pik3ca Tg liver and confirmed their in vivo tumorigenic capacity. Notably, the number and tumor-initiating capacity of Cd44-positive hepatocytes were governed by Kdm3a. As a mechanism in Kdm3a-dependent AP-1 transcription, Kdm3a recruited c-Jun to the AP-1 binding sites of Cd44, Mmp7 and Pdgfrb without affecting c-Jun expression. Moreover, Brg1, a component of the SWI/SNF chromatin remodeling complex, interacted with c-Jun in a Kdm3a-dependent manner and was bound to the AP-1 binding site of these genes. Finally, KDM3A and c-JUN were co-expressed in 33% of human premalignant lesions with PI3K activation. Our data suggest a critical role for KDM3A in the PI3K/AP-1 oncogenic axis and propose a novel strategy for inhibition of KDM3A against liver tumor development under PI3K pathway activation.
It has been reported that EMMPRIN is involved in the regulation of immune response and the induction of MMPs production by fibroblasts. The aim of this study was to describe the intestinal gene ...expression and protein production of EMMPRIN, MMP23 and MMP10 in patients with ulcerative colitis (UC) and Crohn’s disease (CD) and compared them with a control group. Gene expression of EMMPRIN, MMP10 and MMP23B was measured by RT‐PCR. In order to determine EMMPRIN and MMP protein expression, colonic tissues were immunostained. The results of the study showed EMMPRIN gene expression was upregulated in rectal mucosa from active (a)UC versus aCD patients (P = .045), remission (r)CD group (P = .0009) and controls (P < .0001). We detected differences between rUC and aCD (P = .004), rCD (P < .0001) or control group (P < .0001). EMMPRIN showed a higher expression in mucosa (intraepithelial lymphocytes), submucosa and adventitia (endothelial cells) from aCD patients. MMP23 levels were increased in aUC and aCD compared to rUC and rCD and the control group (P = .0001). EMMPRIN+/MMP23+─expressing cells were localized mainly in mucosa, muscular and adventitia from active UC patients. MMP10 gene expression was increased in aUC versus CD patients and the control group (P = .0001). MMP10 gene expression is associated with inflammation in UC patients (P = .0001, r2 = .585). EMMPRIN+/MMP10+─producing cells were found mainly in all intestinal layers and perivascular inflammatory infiltrates from aUC patients. In conclusion, EMMPRIN, MMP23 and MMP10 were upregulated in patients with active UC versus remission UC , CD and control groups suggesting that, they are involved in the inflammatory process.
Silicon nanocrystals, also called quantum dots, have unique optical properties when in the quantum‐confinement regime. These optical properties make silicon nanocrystals promising materials for a ...wide variety of applications ranging from optoelectronic devices to fluorophores in biological imaging. A liquid‐phase synthetic approach is reported using surfactant molecules to control particle growth, producing highly monodisperse silicon particles. The surface of the nanocrystals are capped by functional organic molecules that passivate and protect the silicon particles from oxidation, enabling the particles to be used in hydrophobic and hydrophilic applications. The use of hydrophilic silicon quantum dots as optical probes is illustrated by the imaging of Vero cells.
A simple method for producing uniformly sized nanometer‐scale silicon nanocrystals in inverse micelles with powerful hydride reducing agents is reviewed. The small, monodisperse nanocrystals produce a sharp blue photoluminescence (see figure) resulting from direct bandgap emission. The surface properties of the silicon nanocrystals can be controlled to produce hydrophobic or hydrophilic particles, with an example application in biological imaging presented.
Pluripotent stem cells offer the potential for an unlimited source for cell therapy products. However, there is concern regarding the tumorigenicity of these products in humans, mainly due to the ...possible unintended contamination of undifferentiated cells or transformed cells. Because of the complex nature of these new therapies and the lack of a globally accepted consensus on the strategy for tumorigenicity evaluation, a case-by-case approach is recommended for the risk assessment of each cell therapy product. In general, therapeutic products need to be qualified using available technologies, which ideally should be fully validated. In such circumstances, the developers of cell therapy products may have conducted various tumorigenicity tests and consulted with regulators in respective countries. Here, we critically review currently available in vivo and in vitro testing methods for tumorigenicity evaluation against expectations in international regulatory guidelines. We discuss the value of those approaches, in particular the limitations of in vivo methods, and comment on challenges and future directions. In addition, we note the need for an internationally harmonized procedure for tumorigenicity assessment of cell therapy products from both regulatory and technological perspectives.
Background. Multiple genes have been associated with IBD, and many of these can be linked to alterations in autophagy, UPR, ubiquitination, and metabolic and immune response pathways. The aim of this ...study was to analyze a transcriptomic panel of mediators associated with the inflammatory pathways in the colonic mucosa of UC patients. Patients and Methods. We studied a total of 100 patients with definitive diagnosis of UC (50 active and 50 in remission) and a control group (50 subjects) without endoscopic evidence of intestinal inflammation. Colonic mucosal biopsies were taken by colonoscopy and preserved in RNA later. Gene expression were measured by real-time polymerase chain reaction (RT-PCR). Results. The gene expressions of XBP1, AGR2, HSPA5, UBE2L3, TNFRSF14, LAMP3, FCGR2A, LSP1, CTLA4, SOD2, TDO2, and ALDOB mRNA levels were significantly higher in the colonic mucosa from UC patients (both quiescent and active) as compared to the control group (P<0.05). Conversely, IRGM, ORDML3, UBD, CUL2, CYLD, FOXC2, FOXO4, DOK3, and SNX20 mRNA levels were found to be significantly lower in patients with active disease, as compared to those with active disease (P<0.05). Gene expressions of IRGM, CTLA4, FOXO4, SLC26A3, SLC39A4, SOD2, TDO2, and ALDOB were associated with clinical outcomes, such as medical treatment in response to aminosalicylates, histological remission, clinical course, and evolution. Conclusions: The gene expressions of FOXO4, ALDOB, SOD2, TOD2, SLC26A3, and SLC39A4 were associated with the clinical course and histological activity and are of relevance since these provide the utility of new prognostic markers in IBD. Gene expression signature showed dysregulation in mediators associated with autophagy, ubiquitination, ER stress, oxidative stress, carbohydrate metabolism, solute transport, and T cell regulation in the colonic mucosa from patients with UC, suggesting that these genes could be involved in the pathogenesis of UC.
We report on magnetic and electronic properties of the B-site-ordered double-perovskite La2CrMnO6 films grown by pulsed-laser deposition. The magnetic-field dependence of magnetization curves showed ...hysteresis at low temperatures regardless of the degree of Cr/Mn order and the saturation magnetization became smaller for the higher-Cr/Mn-ordered film. The x-ray absorption spectroscopy and x-ray magnetic circular dichroism measurements suggested antiferromagnetic coupling between Cr3+ and Mn3+ ions, resulting in ferrimagnetism of the B-site-ordered double-perovskite La2CrMnO6. A band structure was established by combining these results together with the synchrotron-radiation photoemission and optical spectra. We discuss the magnetic states among the B-site-ordered La2B′MnO6 (B′:3d transition-metal elements from V to Ni) being basically consistent with the Kanamori-Goodenough rule.
Abstract Shisaka Smelting Co., Ltd. has recovered crude zinc oxide pellets from an electric arc furnace dust (EAF dust) by the Waelz kiln process since 1977. The EAF dust processing line consists of ...a reduction roasting process, a Waelz oxide washing process, and a drying/calcination process. In late years, about 90,000 tons of EAF dust is processed annually at Shisaka. The recovered zinc is sold to zinc smelters as crude zinc oxide pellets, and the amount of production of the pellets is about 40,000 tons per year. Two types of zinc oxide pellets are produced, and the product for electro-refinery requires high quality, especially in fluorine reduction. Most of fluorine are distributed to the clinker in a reduction roasting process, and others are distributed to the Waelz oxide. Conventionally, high-grade crude zinc oxide pellets were produced by washing the Waelz oxide and by volatilizing and separating fluorine under high temperature operation in a drying rotary kiln. However, formation of accretion in the kiln and damage of the shell and refractories of the kiln often occurred under the influence of high temperature operation, and stable consecutive operation of the kiln was difficult. To improve this situation, the fluorine input was reduced by compounding management of EAF dust in the reduction roasting process, and the material residence time in the drying rotary kiln was extended by reducing rotary speed. These improvements resulted in stable consecutive operation under low temperature conditions and increased production of high-grade crude zinc oxide pellets. To improve this situation, the fluorine input was reduced by compounding management of EAF dust in the reduction roasting process, and the material residence time in the drying rotary kiln was extended by reducing rotary speed. These improvements resulted in stable consecutive operation under low temperature conditions and increased production of high-grade crude zinc oxide pellets.
In order to realize superconductivity in cuprates with the T′-type structure, not only chemical substitution (Ce doping) but also postgrowth reduction annealing is necessary. In the case of thin ...films, however, well-designed reduction annealing alone without Ce doping can induce superconductivity in the T′-type cuprates. In order to unveil the origin of superconductivity in the Ce-undoped T′-type cuprates, we have performed bulk-sensitive hard x-ray photoemission and soft x-ray absorption spectroscopy on superconducting and nonsuperconducting Nd2−xCexCuO4 (x=0, 0.15, and 0.19) thin films. By postgrowth annealing, core-level spectra exhibited dramatic changes, which we attributed to the enhancement of core-hole screening in the CuO2 plane and the shift of chemical potential along with changes in the band filling. The result suggests that the superconducting Nd2CuO4 film is doped with electrons despite the absence of the Ce substitution.
► Photo-bioreactor is used for conversion of organic carbon in wastewater to biomass. ► Photosynthetic bacteria grew in the reactor equipped with infrared transmitting filter. ► Photo-bioreactor was ...operated with real fluctuating wastewater in long term (>400d). ► Mixed photosynthetic bacteria culture was characterized by PCR–DGGE method. ► Presence of Rhodopseudomonas palustris and diversity of photosynthetic bacteria were revealed.
Purple non-sulfur bacteria (PNSB) were cultivated by food industry wastewater in the anaerobic membrane photo-bioreactor. Organic removal and biomass production and characteristics were accomplished via an explicit examination of the long term performance of the photo-bioreactor fed with real wastewater. With the support of infra-red light transmitting filter, PNSB could survive and maintain in the system even under the continual fluctuations of influent wastewater characteristics. The average BOD and COD removal efficiencies were found at the moderate range of 51% and 58%, respectively. Observed photosynthetic biomass yield was 0.6g dried solid/g BOD with crude protein content of 0.41g/g dried solid. Denaturing gradient gel electrophoretic analysis (DGGE) and 16S rDNA sequencing revealed the presence of Rhodopseudomonas palustris and significant changes in the photosynthetic bacterial community within the system.
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