ER Stress and Lipid Metabolism in Adipocytes

The role of endoplasmic reticulum (ER) stress is a rapidly emerging field of interest in the pathogenesis of metabolic diseases. Recent studies have shown that chronic activation of ER stress is closely linked to dysregulation of lipid metabolism in several metabolically important cells including hepatocytes, macrophages, β-cells, and adipocytes. Adipocytes are one of the major cell types involved in the pathogenesis of the metabolic syndrome. Recent advances in dissecting the cellular and molecular mechanisms involved in the regulation of adipogenesis and lipid metabolism indicate that activation of ER stress plays a central role in regulating adipocyte function. In this paper, we discuss the current understanding of the potential role of ER stress in lipid metabolism in adipocytes. In addition, we touch upon the interaction of ER stress and autophagy as well as inflammation. Inhibition of ER stress has the potential of decreasing the pathology in adipose tissue that is seen with energy overbalance

Flavonoid Apigenin Inhibits Lipopolysaccharide-Induced Inflammatory Response through Multiple Mechanisms in Macrophages

Background Apigenin is a non-toxic natural flavonoid that is abundantly present in common fruits and vegetables. It has been reported that apigenin has various beneficial health effects such as anti-inflammation and chemoprevention. Multiple studies have shown that inflammation is an important risk factor for atherosclerosis, diabetes, sepsis, various liver diseases, and other metabolic diseases. Although it has been long realized that apigenin has anti-inflammatory activities, the underlying functional mechanisms are still not fully understood. Methodology and Principal Findings In the present study, we examined the effect of apigenin on LPS-induced inflammatory response and further elucidated the potential underlying mechanisms in human THP-1-induced macrophages and mouse J774A.1 macrophages. By using the PrimePCR array, we were able to identify the major target genes regulated by apigenin in LPS-mediated immune response. The results indicated that apigenin significantly inhibited LPS-induced production of pro-inflammatory cytokines, such as IL-6, IL-1β, and TNF-α through modulating multiple intracellular signaling pathways in macrophages. Apigenin inhibited LPS-induced IL-1β production by inhibiting caspase-1 activation through the disruption of the NLRP3 inflammasome assembly. Apigenin also prevented LPS-induced IL-6 and IL-1β production by reducing the mRNA stability via inhibiting ERK1/2 activation. In addition, apigenin significantly inhibited TNF-α and IL-1β-induced activation of NF-κB. Conclusion and Significance Apigenin Inhibits LPS-induced Inflammatory Response through multiple mechanisms in macrophages. These results provided important scientific evidences for the potential application of apigenin as a therapeutic agent for inflammatory diseases

A Dynamic Microblog Network and Information Dissemination in “@” Mode

Social media, especially the microblogs, emerge as a part of our daily life and become a key way to information spread. Thus, information dissemination in the microblog became a research hotspot. Based on some principles that are summarized from the microblog users’ behaviors, this paper proposes a dynamic microblog network model. Through simulations this network has the features of periodicity of average degree, high clustering coefficient, high degree of modularity, and community. Besides, an information dissemination model through “@” in the microblog has been presented. With the microblog network model and the zombie-city model, this paper has modelled an artificial microblog and has simulated the information dissemination in the artificial microblog with different scenes. Therefore, some interesting findings have been presented. (1) Due to a better connectivity, information could spread widely in a random network; (2) information spreads more quickly in a stable microblog network; (3) the decay rate of the relationships will have an effect on information dissemination; that is, with a lower decay rate, information spreads more quickly and widely; (4) the higher active level of users in microblog could promote information spread widely and quickly; (5) the “@” mode of information dissemination makes a high modularity of the information diffusion network

Rumor Diffusion in an Interests-Based Dynamic Social Network

To research rumor diffusion in social friend network, based on interests, a dynamic friend network is proposed, which has the characteristics of clustering and community, and a diffusion model is also proposed. With this friend network and rumor diffusion model, based on the zombie-city model, some simulation experiments to analyze the characteristics of rumor diffusion in social friend networks have been conducted. The results show some interesting observations: (1) positive information may evolve to become a rumor through the diffusion process that people may modify the information by word of mouth; (2) with the same average degree, a random social network has a smaller clustering coefficient and is more beneficial for rumor diffusion than the dynamic friend network; (3) a rumor is spread more widely in a social network with a smaller global clustering coefficient than in a social network with a larger global clustering coefficient; and (4) a network with a smaller clustering coefficient has a larger efficiency

Effects of Dietary Fish Oil on the Depletion of Carcinogenic PAH-DNA Adduct Levels in the Liver of B6C3F1 Mouse

Many carcinogenic polycyclic aromatic hydrocarbons (PAHs) and their metabolites can bind covalently to DNA. Carcinogen-DNA adducts may lead to mutations in critical genes, eventually leading to cancer. In this study we report that fish oil (FO) blocks the formation of DNA adducts by detoxification of PAHs. B6C3F1 male mice were fed a FO or corn oil (CO) diet for 30 days. The animals were then treated with seven carcinogenic PAHs including benzo(a)pyrene (BaP) with one of two doses via a single intraperitoneal injection. Animals were terminated at 1, 3, or 7 d after treatment. The levels of DNA adducts were analyzed by the 32P-postlabeling assay. Our results showed that the levels of total hepatic DNA adducts were significantly decreased in FO groups compared to CO groups with an exception of low PAH dose at 3 d (P = 0.067). Total adduct levels in the high dose PAH groups were 41.36±6.48 (Mean±SEM) and 78.72±8.03 in 109 nucleotides (P = 0.011), respectively, for the FO and CO groups at 7 d. Animals treated with the low dose (2.5 fold lower) PAHs displayed similar trends. Total adduct levels were 12.21±2.33 in the FO group and 24.07±1.99 in the CO group, P = 0.008. BPDE-dG adduct values at 7 d after treatment of high dose PAHs were 32.34±1.94 (CO group) and 21.82±3.37 (FO group) in 109 nucleotides with P value being 0.035. Low dose groups showed similar trends for BPDE-dG adduct in the two diet groups. FO significantly enhanced gene expression of Cyp1a1 in both the high and low dose PAH groups. Gstt1 at low dose of PAHs showed high levels in FO compared to CO groups with P values being 0.014. Histological observations indicated that FO played a hepatoprotective role during the early stages. Our results suggest that FO has a potential to be developed as a cancer chemopreventive agent

Berberine Inhibits HIV Protease Inhibitor-Induced Inflammatory Response by Modulating ER Stress Signaling Pathways in Murine Macrophages

Background HIV protease inhibitor (PI)-induced inflammatory response plays an important role in HIV PI-associated dyslipidemia and cardiovascular complications. This study examined the effect of berberine, a traditional herb medicine, on HIV PI-induced inflammatory response and further investigated the underlying cellular/molecular mechanisms in macrophages. Methodology and Principal Findings Cultured mouse J774A.1 macrophages and primary mouse macrophages were used in this study. The expression of TNF-α and IL-6 were detected by real-time RT-PCR and ELISA. Activations of ER stress and ERK signaling pathways were determined by Western blot analysis. Immunofluorescent staining was used to determine the intracellular localization of RNA binding protein HuR. RNA-pull down assay was used to determine the association of HuR with endogenous TNF-α and IL-6. Berberine significantly inhibited HIV PI-induced TNF-α and IL-6 expression by modulating ER stress signaling pathways and subsequent ERK activation, in turn preventing the accumulation of the RNA binding protein HuR in cytosol and inhibiting the binding of HuR to the 3′-UTRs of TNF-α and IL-6 in macrophages. Conclusions and Significance Inhibition of ER stress represents a key mechanism by which berberine prevents HIV PI-induced inflammatory response. Our findings provide a new insight into the molecular mechanisms of berberine and show the potential application of berberine as a complimentary therapeutic agent for HIV infection

Toward reduction of artifacts in fused images

Most fusion satellite image methodologies at pixel-level introduce false spatial details, i.e.artifacts, in the resulting fusedimages. In many cases, these artifacts appears because image fusion methods do not consider the differences in roughness or textural characteristics between different land covers. They only consider the digital values associated with single pixels. This effect increases as the spatial resolution image increases. To minimize this problem, we propose a new paradigm based on local measurements of the fractal dimension (FD). Fractal dimension maps (FDMs) are generated for each of the source images (panchromatic and each band of the multi-spectral images) with the box-counting algorithm and by applying a windowing process. The average of source image FDMs, previously indexed between 0 and 1, has been used for discrimination of different land covers present in satellite images. This paradigm has been applied through the fusion methodology based on the discrete wavelet transform (DWT), using the à trous algorithm (WAT). Two different scenes registered by optical sensors on board FORMOSAT-2 and IKONOS satellites were used to study the behaviour of the proposed methodology. The implementation of this approach, using the WAT method, allows adapting the fusion process to the roughness and shape of the regions present in the image to be fused. This improves the quality of the fusedimages and their classification results when compared with the original WAT metho