Gastric cancer is the sixth leading cause of cancer‐related death in Taiwan, and the identification of related factors is essential to increase patient survival. ADP‐ribosylation factor 1 (ARF1) was ...initially identified using 2‐D electrophoresis combined with MALDI–time‐of‐flight mass spectrometry. ADP‐ribosylation factor 1 belongs to the Ras superfamily or GTP‐binding protein family and has been shown to enhance cell proliferation. In the current study, we evaluated the potential of ARF1 as a biomarker for gastric cancer detection. ADP‐ribosylation factor 1 mRNA was upregulated in tumor tissues (compared with adjacent non‐tumor tissues, n = 55) in approximately 67.2% of gastric cancer patients. Expression of ARF1 protein was additionally observed using Western blot and immunohistochemistry (IHC) analyses. The clinicopathological correlations of ARF1 were further evaluated. Elevated ARF1 expression was strongly correlated with lymph node metastasis (P = 0.008), serosal invasion (P = 0.046), lymphatic invasion (P = 0.035), and pathological staging (P = 0.010). Moreover, the 5‐year survival rate for the lower ARF1 expression group (n = 50; IHC score < 90) was higher than that of the higher expression group (n = 60; IHC score ≥ 90) (P = 0.0228, log–rank test). To establish the specific function of ARF1 in human gastric cancer, isogenic ARF1‐overexpressing cell lines were prepared. Our results showed that ARF1‐overexpressing clones display enhanced cell proliferation, migration, and invasion. Furthermore, ARF1‐overexpression might contribute to poor prognosis of patients. These findings collectively support the utility of ARF1 as a novel prognostic marker for gastric cancer and its role in cell invasion. Cancer Sci 2012; 103: 1136–1144)
Nintedanib can inhibit processes involved in the progression of fibrosis and can reduce the decline in forced vital capacity in patients with idiopathic pulmonary fibrosis (IPF) and ...fibrotic-interstitial lung disease (fibrotic-ILDs). Although the adverse events associated with nintedanib in IPF patients are well known, its safety in other fibrotic-ILD patients remained unclear.
We searched PubMed, EMBASE, Cochrane CENTRAL and Cochrane CDSR for randomized controlled studies which compared nintedanib with a placebo in ILD patients. We estimated pooled odds ratios (ORs) and 95% confidence intervals (CIs) for adverse events using the DerSimonian-Laird random-effects model.
Six studies with a total of 2,583 patients were included in the meta-analysis. The pooled estimates showed that patients treated with nintedanib had a significantly higher likelihood of having any adverse events (OR = 2.39; 95% CI = 1.71-3.36) or adverse events leading to treatment discontinuation (OR = 1.73; 95% CI = 1.34-2.25). However, they had trend to lower likelihood of having fatal adverse events (OR = 0.69; 95% CI = 0.41-1.14) compared with the placebo group. Use of nintedanib was positively associated with diarrhea (OR = 5.96; 95% CI = 4.35-8.16), nausea (OR = 3.00; 95% CI = 1.93-4.66), vomiting (OR = 3.22; 95% CI = 2.17-4.76) and weight loss (OR = 3.38; 95% CI = 1.1.76-6.47). Whereas, patients treated with nintedanib were less likely to have a cough (OR = 0.73; 95% CI = 0.56-0.96) and dyspnea (OR = 0.70; 95% CI = 0.53-0.94).
Compared to a placebo, nintedanib was associated with a higher risk of adverse events, especially for diarrhea, nausea, vomiting and weight loss, but it was also associated with a lower risk of cough and dyspnea in IPF and fibrotic-ILD patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In recent years, some multiple attribute decision making (MADM) methods have been presented based on interval-valued intuitionistic fuzzy sets (IVIFSs). In this paper, we propose a new MADM method ...based on IVIFSs, the linear programming (LP) methodology, and the extension of the technique for order preference by similarity to ideal solution (TOPSIS) method, where the LP methodology is used to obtain optimal weights of attributes. The proposed method can overcome the drawbacks of the existing methods for MADM in interval-valued intuitionistic fuzzy (IVIF) environments.
Despite the sky-rocketing efficiencies being reported for perovskite solar cells (PSSCs) with several different configurations recently, it is as yet unclear which configuration will prove beneficial ...over others. In this work, we report a novel, inverted PSSC with the configuration of FTO/NiO/meso-Al sub(2)O sub(3)/CH sub(3)NH sub(3)PbI sub(3)/PCBM/BCP/Ag. The first implementation of the hybrid interfacial layer of an ultrathin NiO compact layer (10-20 nm) plus an inert mesoporous Al sub(2)O sub(3) (meso-Al sub(2)O sub(3)) scaffold, featuring high optical transparency and specific dual blocking effect, leads to minimal light absorption loss and interfacial recombination loss. The device performance has been significantly improved with respect to the control PSSCs without the meso-Al sub(2)O sub(3) layer. Synchronized improvements in photovoltage, photocurrent and fill factor lead to a high efficiency of >13%, which is the highest reported so far for NiO based PSSCs. Small hysteresis and stable power output under working conditions have been demonstrated for this type of solar cells. The results also highlight the general and critical importance of interfacial control in PSSCs, and their effects on device performance.
Helicobacter pylori is the most infectious human pathogen that causes gastritis, peptic ulcers and stomach cancer. H. pylori DNA polymerase I (HpPol I) is found to be essential for the viability of ...H. pylori, but its intrinsic property and attribution to the H. pylori DNA replication remain unclear. HpPol I contains a 5′→3′ exonuclease (5′‐Exo) and DNA polymerase (Pol) domain, respectively, but lacks a 3′→5′ exonuclease, or error proofreading activity. In this study, we characterized the 5′‐Exo and Pol functions of HpPol I and found that HpPol I is a multifunctional protein displaying DNA nick translation, strand‐displacement synthesis, RNase H‐like, structure‐specific endonuclease and exonuclease activities. In the in vitro DNA replication assay, we further demonstrated that the 5′‐Exo and Pol domains of HpPol I can cooperate to fill in the DNA gap, remove the unwanted RNA primer from a RNA/DNA hybrid and create a ligatable nick for the DNA ligase A of H. pylori to restore the normal duplex DNA. Altogether, our study suggests that the two catalytic domains of HpPol I may synergistically play an important role in the maturation of Okazaki fragments during the lagging‐strand DNA synthesis in H. pylori. Like the functions of DNA polymerase I in Escherichia coli, HpPol I may involve in both DNA replication and repair in H. pylori.
Helicobacter pylori DNA polymerase I (HpPol I) may involve in the maturation of Okazaki fragments during the lagging‐strand DNA synthesis in H. pylori. HpPol I displays strand‐displacement synthesis, RNase H‐like and structure‐specific endonuclease activities. The 5′→3′ exonuclease and DNA polymerase functions of HpPol I can cooperate to fill in the DNA gap, remove the unwanted RNA primer and create a ligatable nick for the DNA ligase A of H. pylori.
Fruit peel colour is an important agronomic trait for fruit quality. Cytosine methylation plays an important role in gene regulation. Although the DNA methylation level of a single gene is important ...to affect the phenotype of mutation, there are large unknown of difference of the DNA methylation in plant and its mutants.
Using bisulfite sequencing (BS-Seq) and RNA-sequencing (RNA-Seq), we analysed three deep-red-skinned apple (Malus × domestica) mutants (Yanfu 3, YF3; Yanfu 8, YF8; Shannonghong, SNH) and their lighter-skinned parents (Nagafu 2, NF2; Yanfu 3, YF3; Ralls, RL) to explore the different changes in methylation patterns associated with anthocyanin concentrations. We identified 13,405, 13,384, and 10,925 differentially methylated regions (DMRs) and 1987, 956, and 1180 differentially expressed genes (DEGs) in the NF2/YF3, YF3/YF8, and RL/SNH comparisons, respectively. And we found two DMR-associated DEGs involved in the anthocyanin pathway: ANS (MD06G1071600) and F3H (MD05G1074200). These genes exhibited upregulated expression in apple mutants, and differences were observed in the methylation patterns of their promoters. These results suggested that both the regulatory and structural genes may be modified by DNA methylation in the anthocyanin pathway. However, the methylation of structural genes was not the primary reason for expression-level changes. The expression of structural genes may be synergistically regulated by transcription factors and methylation changes. Additionally, the expression of the transcription factor gene MYB114 (MD17G1261100) was upregulated in the deep-red-skinned apple.
Through the analysis of global methylation and transcription, we did not find the correlation between gene expression and the DNA methylation. However, we observed that the upregulated expression of ANS (MD06G1071600) and F3H (MD05G1074200) in apple mutants results in increased anthocyanin contents. Moreover, MYB114 (MD17G1261100) is likely another regulatory gene involved in apple coloration. Our data provided a new understanding about the differences in formation of apple colour mutants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dysregulated maternal nutrition, such as vitamin deficiencies and excessive levels of glucose and fatty acids, increases the risk for congenital heart disease (CHD) in the offspring. However, the ...association between maternal amino‐acid levels and CHD is unclear. Here, it is shown that increased leucine levels in maternal plasma during the first trimester are associated with elevated CHD risk in the offspring. High levels of maternal leucine increase embryonic lysine‐leucylation (K‐Leu), which is catalyzed by leucyl‐tRNA synthetase (LARS). LARS preferentially binds to and catalyzes K‐Leu modification of lysine 339 within T‐box transcription factor TBX5, whereas SIRT3 removes K‐Leu from TBX5. Reversible leucylation retains TBX5 in the cytoplasm and inhibits its transcriptional activity. Increasing embryonic K‐Leu levels in high‐leucine‐diet fed or Sirt3 knockout mice causes CHD in the offspring. Targeting K‐Leu using the leucine analogue leucinol can inhibit LARS activity, reverse TBX5 K‐Leu modification, and decrease the occurrence of CHD in high‐leucine‐diet fed mice. This study reveals that increased maternal leucine levels increases CHD risk in the offspring through inhibition of embryonic TBX5 signaling, indicating that leucylation exerts teratogenic effects during heart development and may be an intervening target of CHD.
Increased gestational leucine levels are significantly associated with risk for congenital heart disease (CHD) in offspring. Increased embryonic lysine‐leucylation (K‐Leu), generated via maternal high‐leucine‐chow feeding, or Sirt3 knockout, causes CHD in the offspring of mice, through elevating embryonic K‐Leu of TBX5 and inhibiting TBX5 activity. Targeting K‐Leu via leucinol reverses K‐Leu modifications and lowers the occurrence of CHD in mice.
Direct Cu-to-Cu bonding was achieved at temperatures of 150-250 °C using a compressive stress of 100 psi (0.69 MPa) held for 10-60 min at 10(-3) torr. The key controlling parameter for direct bonding ...is rapid surface diffusion on (111) surface of Cu. Instead of using (111) oriented single crystal of Cu, oriented (111) texture of extremely high degree, exceeding 90%, was fabricated using the oriented nano-twin Cu. The bonded interface between two (111) surfaces forms a twist-type grain boundary. If the grain boundary has a low angle, it has a hexagonal network of screw dislocations. Such network image was obtained by plan-view transmission electron microscopy. A simple kinetic model of surface creep is presented; and the calculated and measured time of bonding is in reasonable agreement.
Vimentin intermediate filaments (VIFs), expressed in most mesenchymal and cancer cells, undergo dramatic reorganization during cell migration; however, the mechanism remains obscure. This study ...demonstrates that upon growth-factor stimulation, Src directly phosphorylates vimentin at Tyr117, leading to VIF disassembly into squiggles and particles at the cell edge during lamellipodia formation. The protein tyrosine phosphatase SHP2 counteracted the Src effects on VIF tyrosine phosphorylation and organization. VIFs formed by vimentin Y117D mutant were more soluble and dynamic than those formed by the wild-type and Y117F mutant. Increased expression of vimentin promoted growth-factor induced lamellipodia formation and cell migration, whereas the mutants suppressed both. The vimentin-induced increase in lamellipodia formation correlated with the activation of Rac and Vav2, with the latter associated with VIFs and recruited to the plasma membrane upon growth-factor stimulation. These results reveal a novel mechanism for regulating VIF dynamics through Src and SHP2 and demonstrate that proper VIF dynamics are important for Rac activation and cell migration.
The poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is partially attributed to the invasive and metastatic behavior of this disease. Laminin subunit beta-3 (LAMB3) encodes one ...of the three subunits of LM-332, an extracellular matrix protein secreted by cultured human keratinocytes. In addition, LAMB3 is involved in the invasive and metastatic abilities of some types of cancer, including colon, pancreas, lung, cervix, stomach, and prostate cancer, but the role and mechanism of LAMB3 in PDAC have not been previously determined. Herein, we tentatively investigated the role of LAMB3 in the malignant biological behavior of PDAC. In this study, we demonstrated that LAMB3 is upregulated in PDAC. Inhibition of LAMB3 abrogated the tumorigenic outcomes of PI3K/Akt signaling pathway activation, including those involving cell cycle arrest, cell apoptosis, proliferation, invasion and migration in vitro, and tumor growth and liver metastasis in vivo. Our results showed that LAMB3 could mediate cell cycle arrest and apoptosis in PDAC cells and alter the proliferative, invasive, and metastatic behaviors of PDAC by regulating the PI3K/Akt signaling pathway. LAMB3 may be a novel therapeutic target for the treatment of PDAC in the future.
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