Image_1_Astragaloside IV Inhibits Triglyceride Accumulation in Insulin-Resistant HepG2 Cells via AMPK-Induced SREBP-1c Phosphorylation.TIF

<p>Objective: Insulin resistance (IR) is a risk factor for non-alcoholic fatty liver disease (NAFLD), which is characterized by lipid accumulation in hepatocytes. AMP-activated protein kinase (AMPK)-induced sterol regulatory element binding protein-1c (SREBP-1c) phosphorylation is crucial for proper regulation of lipid metabolism in the liver. Astragaloside IV (AST-IV) was found to decrease lipid accumulation in hepatocytes by activating AMPK, which is required to regulate lipid metabolism in liver tissue by inducing SREBP-1c phosphorylation.</p><p>Method: To evaluate the direct effect of AST on lipid accumulation in hepatocytes with IR and elucidate the underlying mechanisms, we induced IR in HepG2 cells, and used compound C and 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) (an AMPK inhibitor and agonist, respectively) as control substances. We evaluated glucose, triglyceride (TG), and non-esterified fatty acid (NEFA) production, as well as SREBP-1c transcription, SREBP-1c protein expression, and downstream gene expression with or without the presence of AST. We also investigated whether phosphorylation of SREBP-1c at Ser372 was required for AST function.</p><p>Results: We found that AST attenuated IR and lipid accumulation in HepG2 cells. As an AMPK activator, AST promoted gene expression and activation of AMPK by increasing phosphorylation of AMPKa. AST also inhibited translocation of SREBP-1c into the nucleus of insulin-resistant HepG2 cells by inducing phosphorylation of SREBP-1c at Ser372.</p><p>Conclusion: This study demonstrated that AST attenuates IR and lipid accumulation in HepG2 cells by regulating AMPK-dependent phosphorylation of SREBP-1c at Ser372, suggesting AST as a promising drug for treating hepatic steatosis.</p

Clinical utility of the modified Glasgow prognostic score in lung cancer: A meta-analysis

<div><p>Objective</p><p>To perform a meta-analysis of prospective and retrospective studies exploring the association of the modified Glasgow prognostic score (mGPS) with overall survival (OS) in patients with lung cancer.</p><p>Methods</p><p>Relevant studies were identified by searching the Cochrane Library, Web of Science, Embase and PubMed until April 16, 2017. We combined hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the correlation between mGPS and OS in patients with lung cancer.</p><p>Results</p><p>Eleven studies involving 5817 participants from several countries were included in the meta-analysis. In a pooled analysis of all studies, elevated mGPS predicted poorer OS (HR = 1.77; 95% CI: 1.35–2.31; P<0.05). Subgroup analyses stratified by mGPS showed that mGPS of 1 or 2 and mGPS≥1 were predictive of poorer OS and that the HR for mGPS of 2 (HR = 5.82; 95% CI: 1.85–18.22; P = 0.003) was significantly greater than that for mGPS of 1 (HR = 1.74; 95% CI: 1.24–2.45; P = 0.001) and mGPS≥1 (HR = 1.42; 95% CI: 1.14–1.76; P = 0.002). Among patients undergoing surgery, elevated mGPS had a non-significant correlation with reduced OS (HR = 2.48; 95% CI: 0.90–6.85; P = 0.079), whereas the correlation was significant for patients receiving chemotherapy or other palliative treatment (HR = 1.74; 95% CI: 1.31–2.30; P<0.05).</p><p>Conclusions</p><p>Our findings indicate that mGPS may have prognostic value in lung cancer, as we detected a significant association between elevated mGPS and poorer OS. The association between mGPS and poorer OS was non-significant among patients undergoing surgery, which may be attributable to lower tumor load. However, further studies are warranted to draw firm conclusions.</p></div

Begg’s funnel plot of publication bias testing for OS in lung cancer.

<p>Begg’s funnel plot of publication bias testing for OS in lung cancer.</p

Hindered Phenol Derivative as a Multifunctional Additive in Lithium Complex Grease

This paper describes 3-(3,5-Di<i>tert</i>-butyl-4-hydroxy-phenyl)-propionic acid 2-(4-meth yl-thiazol-5-yl)-ethyl ester (BHMT) as a high-performance multifunctional additive in lithium complex grease (LCG). The tribological properties and antioxidant behaviors of BHMT were evaluated by the tribological test and thermal analysis, respectively, and compared with those of zinc dialkyldithiophosphate (ZDDP). The tribochemical film BHMT generated on the worn surface was analyzed by X-ray photoelectron spectroscopy (XPS). Tribological results indicated that BHMT exhibited better friction-reduction and antiwear properties than ZDDP. The thermal analysis demonstrated that the antioxidation ability of BHMT was superior to that of ZDDP. Moreover, XPS results showed that lubrication film composed of iron oxide, iron sulfate, and nitrogen oxide was formed on the worn surface, which was an explicit explanation of the tribochemical mechanism of BHMT

Forest plot of the association between mGPS and OS in patients with lung cancer.

<p>Forest plot of the association between mGPS and OS in patients with lung cancer.</p

Sensitivity analysis of the relationship between mGPS and OS in lung cancer.

<p>Sensitivity analysis of the relationship between mGPS and OS in lung cancer.</p

Ethylene Polymerization by Dinuclear Xanthene-Bridged Imino- and Aminopyridyl Nickel Complexes

A series of xanthene-bridged dinucleating ligands bearing imino- and aminopyridyl moieties and their nickel complexes were synthesized and characterized. The properties of these dinuclear complexes in ethylene polymerization were studied in comparison with the corresponding mononuclear nickel complexes. The iminopyridyl dinuclear nickel complexes activated by methylaluminoxane (MAO) showed higher catalytic activities (up to 2.2 × 10⁶ g of PE (mol Ni)⁻¹ h^–1), higher molecular weights, and produced polyethylene with much lower branching density (27/1000C) than their mononuclear analogues. Similar trends were observed for the aminopyridyl dinuclear complexes. A metal–metal cooperativity effect was proposed to be able to slow down the β<i>-</i>hydride elimination and the corresponding chain-walking process. These results clearly demonstrated the great potentials of dinuclear nickel catalysts with the xanthene-bridged coordination modes in controlling the ethylene polymerization process as well as the microstructures of the resulting polyethylene products

Begg’s funnel plot of publication bias testing for OS in lung cancer.

<p>Begg’s funnel plot of publication bias testing for OS in lung cancer.</p

Flow chart of study selection.

<p>Flow chart of study selection.</p

<i>Mycobacterium tuberculosis</i>-Specific Phagosome Proteome and Underlying Signaling Pathways

The phagosome is very important to host immunity and tissue homeostasis maintenance. The destiny of the phagosome is closely associated with the outcome of the pathogen within. Most pathogens are successfully delivered to the lysosome and destroyed via the fusion of the phagosome with the lysosome. <i>Mycobacterium tuberculosis</i> has evolved multiple tactics to deflect the normal fusion process, such as delaying the phagosome maturation and acidification, thereby evading the immune recognition and subsequent elimination. Identification of the specific constituents of <i>M. tuberculosis</i> phagosome and the underlying signaling pathways are pivotal to define the key molecular features of this process and better targets to control this recalcitrant pathogen. Proteomic profiling is a comprehensive approach to define the protein inventory. In this review, currently available mycobacteria-containing phagosome proteome data were compiled. Ten putative evolutionarily conserved phagosome proteins were summarized. Unique proteins of the <i>M. tuberculosis</i>-containing phagosome proteome were compiled via comparison with other phagosomes, especially the inert latex bead phagosome. Signaling events associated with these unique proteins, such as Rab GTPase and PI3P, were also found and discussed. The data will facilitate better characterization of the <i>M. tuberculosis</i> specific phagosome constituents and involved signaling, and host-derived targets for better tuberculosis control