6-Gingerol Inhibits Growth of Colon Cancer Cell LoVo via Induction of G2/M Arrest

6-Gingerol, a natural component of ginger, has been widely reported to possess antiinflammatory and antitumorigenic activities. Despite its potential efficacy against cancer, the anti-tumor mechanisms of 6-gingerol are complicated and remain sketchy. In the present study, we aimed to investigate the anti-tumor effects of 6-gingerol on colon cancer cells. Our results revealed that 6-gingerol treatment significantly reduced the cell viability of human colon cancer cell, LoVo, in a dose-dependent manner. Further flow cytometric analysis showed that 6-gingerol induced significant G2/M phase arrest and had slight influence on sub-G1 phase in LoVo cells. Therefore, levels of cyclins, cyclin-dependent kinases (CDKs), and their regulatory proteins involved in S-G2/M transition were investigated. Our findings revealed that levels of cyclin A, cyclin B1, and CDK1 were diminished; in contrast, levels of the negative cell cycle regulators p27Kip1 and p21Cip1 were increased in response to 6-gingerol treatment. In addition, 6-gingerol treatment elevated intracellular reactive oxygen species (ROS) and phosphorylation level of p53. These findings indicate that exposure of 6-gingerol may induce intracellular ROS and upregulate p53, p27Kip1, and p21Cip1 levels leading to consequent decrease of CDK1, cyclin A, and cyclin B1 as result of cell cycle arrest in LoVo cells. It would be suggested that 6-gingerol should be beneficial to treatment of colon cancer

In vitro and in vivo targeted delivery of IL-10 interfering RNA by JC virus-like particles

<p>Abstract</p> <p>Background</p> <p>RNA interference (RNAi) is a powerful tool to silence gene expression post-transcriptionally. Delivering sequences of RNAi <it>in vivo </it>remains a problem. The aim of this study was to use JC virus (JCV) virus-like particles (VLPs) as a vector for delivering RNAi in silencing the cytokine gene of IL-10.</p> <p>Methods</p> <p>JCV VLPs were generated by recombinant JCV VP1 protein in yeast expression system. DNA fragment containing IL-10 shRNA was packaged into VLPs by osmotic shock.</p> <p>Results</p> <p>In RAW 264.7 cells, IL-10 shRNA was found to reduce IL-10 expression by 85 to 89%, as compared with VLPs alone. IL-10 shRNA did not cross-react with TNF-alpha mRNA or influence the expression of TNF-alpha. In BALB/c mice IL-10 shRNA could reduce 95% of IL-10 secretion. Surprisingly, it also down regulated TNF-alpha expression.</p> <p>Conclusions</p> <p>We show for the first time that JCV VLPs empty capsids are competent vectors to deliver RNAi and are nontoxic to cells, suggesting that JCV VLPs is an efficient agent to deliver RNAi in both murine macrophage cells and BALB/c mice. This system provides an efficient means for delivering the RNAi for gene therapy purposes.</p

Glycine tomentella Hayata inhibits IL-1β and IL-6 production, inhibits MMP-9 activity, and enhances RAW264.7 macrophage clearance of apoptotic cells

<p>Abstract</p> <p>Background</p> <p>To assess the effects of <it>Glycine tomentella </it>Hayata (GTH), a traditional herbal medicine for treatment of rheumatic diseases on the expression of the proinflammatory cytokines and on the clearance of apoptotic cells by macrophages.</p> <p>Methods</p> <p>RAW264.7 cells were cultured with lipopolysaccharide (LPS) in the presence or absence of ethanol extract of GTH. The expression of proinflammatory cytokines IL-1β, IL-6, and TNF-α, and inducible nitric oxide synthase (iNOS) and transglutaminase 2 (TG2) were assayed by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Matrix metalloproteinase (MMP)-2 and MMP-9 were assayed by gelatin zymography. For detecting uptake of apoptotic cells, RAW264.7 cells were cultured with carboxyfluorescein diacetate (CFDA)-stained apoptotic cells and assayed by flow cytometry.</p> <p>Results</p> <p>The major components of GTH analyzed by high-performance liquid chromatography (HPLC) chromatogram were daidzein (42.5%), epicatechin (28.8%), and naringin (9.4%).</p> <p>GTH treatment inhibited the expression of proinflammatory cytokines IL-1β, IL-6 and MMP-9 but did not affect the expression of TNF-α and iNOS. GTH significantly enhanced the expression of TG2 and the clearance of apoptotic cells by RAW264.7 macrophages.</p> <p>Conclusions</p> <p>GTH inhibits proinflammatory cytokine secretion and MMP-9 activity, enhances apoptotic cell uptake and up-regulates TG2 expression. Our data show that GTH might have beneficial effects on rheumatic diseases.</p

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ABSTRACT. Objective. To examine (1) the risk of death from cardiovascular disease (CVD) and from all causes in patients with gout who do not undergo urate-lowering therapy (ULT), and (2) the effect of ULT on mortality risk in patients with gout. Methods. In this prospective case-matched cohort study, 40,623 Taiwanese individuals aged ≥ 17 years were followed for 6.5 years. Mortality rate was compared between 1189 patients with gout who did not receive ULT and reference subjects (no gout, no ULT) matched for age, sex, and the index date of gout diagnosis (1:3 patients with gout/reference subjects), and between 764 patients with gout who received ULT and 764 patients with gout who did not receive ULT matched 1-to-1 based on their propensity score and the index date of ULT prescription

Transglutaminase 2 Contributes to Apoptosis Induction in Jurkat T Cells by Modulating Ca(2+) Homeostasis via Cross-Linking RAP1GDS1

BACKGROUND: Transglutaminase 2 (TG2) is a protein cross-linking enzyme known to be associated with the in vivo apoptosis program of T cells. However, its role in the T cell apoptosis program was not investigated yet. RESULTS: Here we report that timed overexpression of both the wild type (wt) and the cross-linking mutant of TG2 induced apoptosis in Jurkat T cells, the wt being more effective. Part of TG2 colocalised with mitochondria. WtTG2-induced apoptosis was characterized by enhanced mitochondrial Ca(2+) uptake. Ca(2+)-activated wtTG2 cross-linked RAP1, GTP-GDP dissociation stimulator 1, an unusual guanine exchange factor acting on various small GTPases, to induce a yet uncharacterized signaling pathway that was able to promote the Ca(2+) release from the endoplasmic reticulum via both Ins3P and ryanodine sensitive receptors leading to a consequently enhanced mitochondrial Ca(2+)uptake. CONCLUSIONS: Our data indicate that TG2 might act as a Ca(2+) sensor to amplify endoplasmic reticulum-derived Ca(2+) signals to enhance mitochondria Ca(2+) uptake. Since enhanced mitochondrial Ca(2+) levels were previously shown to sensitize mitochondria for various apoptotic signals, our data demonstrate a novel mechanism through which TG2 can contribute to the induction of apoptosis in certain cell types. Since, as compared to knock out cells, physiological levels of TG2 affected Ca(2+) signals in mouse embryonic fibroblasts similar to Jurkat cells, our data might indicate a more general role of TG2 in the regulation of mitochondrial Ca(2+) homeostasis

Do Neutrophils Play a Role in Establishing Liver Abscesses and Distant Metastases Caused by Klebsiella pneumoniae?

Serotype K1 Klebsiella pneumoniae is a major cause of liver abscesses and endophthalmitis. This study was designed to identify the role of neutrophils in the development of distant metastatic complications that were caused by serotype K1 K. pneumoniae. An in vitro cellular model was used to assess serum resistance and neutrophil-mediated killing. BALB/c mice were injected with neutrophils containing phagocytosed K. pneumoniae. Serotype K1 K. pneumoniae was significantly more resistant to serum killing, neutrophil-mediated phagocytosis and intra-cellular killing than non-K1 isolates (p<0.01). Electron microscopic examination had similar findings as in the bioassay findings. Intraperitoneal injection of neutrophils containing phagocytosed serotype K1 K. pneumoniae led to abscess formation in multiple sites including the subcutaneous tissue, lung, and liver, whereas no abscess formation was observed in mice injected with non-K1 isolates. The resistance of serotype K1 K. pneumoniae to complement- and neutrophil-mediated intracellular killing results in the dissemination of K. pneumoniae via the bloodstream. Escape from neutrophil intracellular killing may contribute to the dissemination and establishment of distant metastases. Thus, neutrophils play a role as a vehicle for helping K. pneumoniae and contributing to the establishment of liver abscess and distant metastatic complications

The Saharan Air Layer and the Fate of African Easterly Waves—NASA's AMMA Field Study of Tropical Cyclogenesis

In 2006, NASA led a field campaign to investigate the factors that control the fate of African easterly waves (AEWs) moving westward into the tropical Atlantic Ocean. Aircraft and surface-based equipment were based on Cape Verde's islands, helping to fill some of the data void between Africa and the Caribbean. Taking advantage of the international African Monsoon Multidisciplinary Analysis (AMMA) program over the continent, the NASA–AMMA (NAMMA) program used enhanced upstream data, whereas NOAA aircraft farther west in the Atlantic studied several of the storms downstream. Seven AEWs were studied during AMMA, with at least two becoming tropical cyclones. Some of the waves that did not develop while being sampled near Cape Verde likely intensified in the central Atlantic instead. NAMMA observations were able to distinguish between the large-scale wave structure and the smaller-scale vorticity maxima that often form within the waves. A special complication of the east Atlantic environment is the Saharan air layer (SAL), which frequently accompanies the AEWs and may introduce dry air and heavy aerosol loading into the convective storm systems in the AEWs. One of the main achievements of NAMMA was the acquisition of a database of remote sensing and in situ observations of the properties of the SAL, enabling dynamic models and satellite retrieval algorithms to be evaluated against high-quality real data. Ongoing research with this database will help determine how the SAL influences cloud micro-physics and perhaps also tropical cyclogenesis, as well as the more general question of recognizing the properties of small-scale vorticity maxima within tropical waves that are more likely to become tropical cyclones

Drying colloidal systems: laboratory models for a wide range of applications

The drying of complex fluids provides a powerful insight into phenomena that take place on time and length scales not normally accessible. An important feature of complex fluids, colloidal dispersions and polymer solutions is their high sensitivity to weak external actions. Thus, the drying of complex fluids involves a large number of physical and chemical processes. The scope of this review is the capacity to tune such systems to reproduce and explore specific properties in a physics laboratory. A wide variety of systems are presented, ranging from functional coatings, food science, cosmetology, medical diagnostics and forensics to geophysics and art