Inhibitory effect of selenomethionine on carcinogenesis in the model of human colorectal cancer in vitro and its link to the Wnt/β-catenin pathway

Selenium compounds have been implicated as anticancer agents; however, the mechanism of their inhibitory action against cancer development has not been extensively investigated. A constitutive activation of the Wnt/β-catenin pathway is a central event in colorectal carcinogenesis. In this pathway, excessive cell proliferation is initiated by generation of β-catenin followed by overexpression of proto-oncogenes, such as c-Myc. It is believed that under physiological conditions the level of c-Myc is efficiently controlled by accessibility of the β-catenin protein through the process of phosphorylation by glycogen synthase kinase 3β (GSK-3β). Here, we determined whether selenomethionine (SeMet) can inhibit cell growth and affect the Wnt/β-catenin pathway in the HT-29 human colorectal cancer cells in vitro. The effective cytotoxic doses of SeMet have been selected after 48 h of incubation of this compound with colorectal cancer HT-29 cell line. MTT assay was used to assess cell viability and the protein and mRNA levels of β-catenin and c-Myc were determined by Western blotting and qPCR, respectively. SeMet potently inhibited growth of HT-29 cells, significantly decreased level of the β-catenin protein and mRNA concentration, down-regulated the c-Myc gene expression and up-regulated the pro-apoptotic Bax protein level. Moreover, SeMet increased the level of GSK-3β phosphorylated at serine 9 (S9) and significantly increased the level of β-catenin phosphorylated at S33 and S37. We conclude that SeMet suppresses growth of HT-29 colorectal cancer cells by a mechanism linked to the Wnt/β-catenin pathway, however, degradation of β-catenin may occur independently of GSK-3β catalytic activity and its phosphorylation status

MicroRNAs and chronic inflammation contribution to gastrointestinal integrity

Recent studies have revealed that chronic inflammation represents a major basis for different forms of human malignancies. Chronic inflammations are involved in the pathogenesis of 15-25% of human malignancies. Gastrointestinal (GI) cancer is one of the most common causes of mortality in the European Union. The mechanisms leading to cancer development and its progression are not completely understood. Advances are required both in early detection and therapy of GI cancers. There are many factors connecting inflammation and cancer. Cytokines that are small protein molecules regulating growth, differentiation, development and immune response mechanisms in cells. Overexpression of cyclooxynenase-2 is associated with decreased apoptosis, cell to cell adhesion, increased proliferation and angiogenesis contributes to the increased immunosuppresion and mediates carcinogenetic effects. MicroRNAs are regarded as a novel class of gene expression regulators. They are gene-silencing RNAs which negatively regulate gene expression. After binding to target mRNAs they lead either to mRNA destruction or inhibition of translation. Hence, they can play an important role in carcinogenesis. Currently, almost all of the miRNA-related studies on cancers based on the different expression profile of miRNAs in cancer cells compared to normal cells. In summary, miRNAs, proinflammatory cytokines and other factors, may be involved in cancer development based on chronic inflammation by controlling cell differentiation and apoptosis. Assessing the role of miRNAs will provide the new insights on their contribution to the link between chronic inflammation and subsequent cancer, and new markers for cancer diagnoses and cancer therapy

Microstructure Influence of SACX0307-TiO2 Composite Solder Joints on Thermal Properties of Power LED Assemblies

The effect of the microstructure of solder joints on the thermal properties of power LEDs was investigated. Solder joints were prepared with different solder pastes, namely 99Sn0.3Ag0.7Cu (as reference solder) and reinforced 99Sn0.3Ag0.7Cu-TiO2 (composite solder). TiO2 ceramic was used at 1 wt% and with two different primary particle sizes, which were 20nm (nano) and 200nm (submicron). The thermal resistance, the electric thermal resistance, and the luminous efficiency of the power LED assemblies were measured. Furthermore, the microstructure of the different solder joints was analyzed on the basis of cross-sections using scanning electron and optical microscopy. It was found that the addition of submicron TiO2 decreased the thermal and electric thermal resistances of the light sources by 20% and 16%, respectively, and it slightly increased the luminous efficiency. Microstructural evaluations showed that the TiO2 particles were incorporated at the Sn grain boundaries and at the interface of the intermetallic layer and the solder bulk. This caused considerable refinement of the Sn grain structure. The precipitated TiO2 particles at the bottom of the solder joint changed the thermodynamics of Cu6Sn5 formation and enhanced the spalling of intermetallic grain to solder bulk, which resulted in a general decrease in the thickness of the intermetallic layer. These phenomena improved the heat paths in the composite solder joints, and resulted in better thermal and electrical properties of power LED assemblies. However, the TiO2 nanoparticles could also cause considerable local IMC growth, which could inhibit thermal and electrical improvements

Mineralogy and deformation structures in components of clastic sediments from the Morasko meteorite lake

The paper presents mineralogical analysis of sediments of the biggest lake formed on the Morasko Meteorite Reserve (Poland) in terms of presence of matter of their origin. The lake are filled by phytogenic sediments at the top, while at their bottom occur Neogene clays. The main components are: clay minerals in fine fraction and quartz and feldspars in coarse sandy fractions. The presence of disturbed ferrous zones suggests the existence of a dynamic factor that caused deformations in the sediments. Cavities, crevices, cracks, and traces of parching or fragmentation of mineral material can be interpreted as deformations related to the impact of meteorite fragments in non-consolidated soft sediments in the Morasko meteorite nature reserve. Meteorite fragments that left numerous deformed structures most probably constituted meteorite debris that originated from the fragmentation of the meteorite before its impact

The influence of SACX0307-ZnO nano-composite solder alloys on the optical and thermal properties of power LEDs

Purpose This paper aims to present the results of investigations that show the influence of ZnO composite soldering paste on the optical and thermal parameters of power LEDs. Design/methodology/approach ZnO nano-composite solder alloys were produced via the ball milling process from the solder paste SACX0307 (Sn99Ag0.3Cu0.7) and 1.0 wt.% of ZnO nanoparticle reinforcements with different primary particle sizes (200 nm, 100 nm, and 50 nm). Power LEDs were soldered onto a metal core printed circuit board (MCPCB). A self-designed LED test system was used to measure the thermal and optical characteristics of the LEDs. Findings The influence of the soldering paste on the thermal and optical parameters of LEDs was observed. In all solder alloys, ZnO ceramic reinforcement increased the thermal parameters of LEDs and decreases their luminous efficiency. Thermal resistance values were10% higher, and junction temperature change over ambient temperature was 20% higher for the samples soldered with composite solder pastes, as compared to the reference sample. At the same time, luminous efficiency dropped by 32%. Originality/value The results prove that ZnO ceramic reinforcement of solder paste influences the thermal properties of solder joints. As it was proven, the quality of the solder joints influences the whole assembly

Exogenous asymmetric dimethylarginine (ADMA) in pathogenesis of ischemia-reperfusion-induced gastric lesions : interaction with protective nitric oxide (NO) and calcitonin gene-related peptide (CGRP)

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthesis inhibitor and pro-inflammatory factor. We investigated the role of ADMA in rat gastric mucosa compromised through 30 min of gastric ischemia (I) and 3 h of reperfusion (R). These I/R animals were pretreated with ADMA with or without the combination of l-arginine, calcitonin gene-related peptide (CGRP) or a small dose of capsaicin, all of which are known to afford protection against gastric lesions, or with a farnesoid X receptor (FXR) agonist, GW 4064, to increase the metabolism of ADMA. In the second series, ADMA was administered to capsaicin-denervated rats. The area of gastric damage was measured with planimetry, gastric blood flow (GBF) was determined by H2-gas clearance, and plasma ADMA and CGRP levels were determined using ELISA and RIA. ADMA significantly increased I/R-induced gastric injury while significantly decreasing GBF, the luminal NO content, and the plasma level of CGRP. This effect of ADMA was significantly attenuated by pretreatment with CGRP, l-arginine, capsaicin, or a PGE2 analogue. In GW4064 pretreated animals, the I/R injury was significantly reduced and this effect was abolished by co-treatment with ADMA. I/R damage potentiated by ADMA was exacerbated in capsaicin-denervated animals with a further reduction of CGRP. Plasma levels of IL-10 were significantly decreased while malonylodialdehyde (MDA) and plasma TNF-α contents were significantly increased by ADMA. In conclusion, ADMA aggravates I/R-induced gastric lesions due to a decrease of GBF, which is mediated by a fall in NO and CGRP release, and the enhancement of lipid peroxidation and its pro-inflammatory properties

Long-term Helicobacter pylori infection switches gastric epithelium reprogramming towards cancer stem cell-related differentiation program in Hp-activated gastric fibroblast-TGFβTGF\beta dependent manner

Helicobacter pylori (Hp)-induced inflammatory reaction leads to a persistent disturbance of gastric mucosa and chronic gastritis evidenced by deregulation of tissue self-renewal and local fibrosis with the crucial role of epithelial-mesenchymal transition (EMT) in this process. As we reported before, Hp activated gastric fibroblasts into cells possessing cancer-associated fibroblast properties (CAFs), which secreted factors responsible for EMT process initiation in normal gastric epithelial RGM1 cells. Here, we showed that the long-term incubation of RGM1 cells in the presence of Hp-activated gastric fibroblast (Hp-AGF) secretome induced their shift towards plastic LGR5+/Oct4$^{high}$/Sox-2$^{high}$/c-Myc$^{high}$/Klf4$^{low}$ phenotype (l.t.EMT+RGM1 cells), while Hp-non-infected gastric fibroblast (GF) secretome prompted a permanent epithelial-myofibroblast transition (EMyoT) of RGM1 cells favoring LGR−/Oct4$^{high}$/Sox2$^{low}$/c-Myc$^{low}$/Klf4$^{high}$ phenotype (l.t.EMT-RGM1 cells). TGFβ1 rich secretome from Hp-reprogrammed fibroblasts prompted phenotypic plasticity and EMT of gastric epithelium, inducing pro-neoplastic expansion of post-EMT cells in the presence of low TGFβR1 and TGFβR2 activity. In turn, TGFβR1 activity along with GF-induced TGFβR2 activation in l.t.EMT-RGM1 cells prompted their stromal phenotype. Collectively, our data show that infected and non-infected gastric fibroblast secretome induces alternative differentiation programs in gastric epithelium at least partially dependent on TGFβ signaling. Hp infection-activated fibroblasts can switch gastric epithelium microevolution towards cancer stem cell-related differentiation program that can potentially initiate gastric neoplasm