Recombinant FGF21 Attenuates Polychlorinated Biphenyl-Induced NAFLD/NASH by Modulating Hepatic Lipocalin-2 Expression

Although recent studies have demonstrated that polychlorinated biphenyls (PCB) exposure leads to toxicant-associated steatohepatitis, the underlying mechanism of this condition remains unsolved. Male C57Bl/6 mice fed a standard diet (SD) or 60% high fat diet (HFD) were exposed to the nondioxin-like PCB mixture Aroclor1260 or dioxin-like PCB congener PCB126 by intraperitoneal injection for a total of four times for six weeks. We observed hepatic injury, steatosis, inflammation, and fibrosis in not only the Aroclor1260-treated mice fed a HFD but the PCB126-treated mice fed either a SD or a HFD. We also observed that both types of PCB exposure induced hepatic iron overload (HIO). Noticeably, the expression of hepatic lipocalin-2 (LCN2) was significantly increased in the PCB-induced nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) models. The knockdown of LCN2 resulted in improvement of PCB-induced lipid and iron accumulation in vitro, suggesting that LCN2 plays a pivotal role in PCB-induced NAFLD/NASH. We observed that recombinant FGF21 improved hepatic steatosis and HIO in the PCB-induced NAFLD/NASH models. Importantly, recombinant FGF21 reduced the PCB-induced overexpression of hepatic LCN2 in vivo and in vitro. Our findings indicate that recombinant FGF21 attenuates PCB-induced NAFLD/NASH by modulating hepatic lipocalin-2 expression. Our data suggest that hepatic LCN2 might represent a suitable therapeutic target for improving PCB-induced NAFLD/NASH accompanying HIO.     

Cellular Regulation of Kynurenic Acid-Induced Cell Apoptosis Pathways in AGS Cells

Kynurenic acid was included in the three compounds (caffeic acid, chlorogenic acid, and kynurenic acid) that showed high antioxidant and anti-inflammatory potential among the phenolic compounds contained in Gynura procumbens. In this study, the mechanism of cancer cell death induced by kynurenic acid (KYNA), which has the highest molecular binding affinity, in the gastric cancer cell line AGS was confirmed in molecular docking analysis. KYNA showed the most cancer cell death effect on AGS cells among several gastric cancer cell lines (MKN, AGS, and SNU). AGS cells were used for later experiments, and KYNA concentrations of 0, 150, 200, and 250 µM were used. KYNA inhibited cell migration and proliferation in AGS cells in a concentration-dependent manner. G2/M phase cell cycle arrest and reduction of related proteins (Cdc25C, CDK1 and CyclinB1) were confirmed in KYNA-treated AGS cells. Apoptosis of KYNA-treated AGS cells was confirmed by Annexin V/propidium iodide (PI) staining flow cytometry analysis. As a result of morphological chromatin condensation through DAPI (4′,6-diamidino-2-phenylindole), intense blue fluorescence was confirmed. The mechanism of apoptosis induction of KYNA-treated AGS cells was confirmed by western blotting. In the extrinsic pathway, apoptosis induction markers FasL, Fas, and Caspase-3 and -8 were increased in a concentration-dependent manner upon KYNA treatment. In the intrinsic pathway, the expression of anti-apoptotic factors PI3K, AKT, and Bcl-xL was down-regulated, and the expression of apoptosis-inducing factors BAD, Bak, Bax, Cytochrom C, and Caspase-9 was up-regulated. Therefore, in the present study, we strongly imply that KYNA induces apoptosis in AGS gastric cancer cells. This suggests that KYNA, a natural compound, could be the basis for drug for the treatment of gastric cancer.     

High-Intensity Focused Ultrasound Induces Adipogenesis via Control of Cilia in Adipose-Derived Stem Cells in Subcutaneous Adipose Tissue

During skin aging, the volume of subcutaneous adipose tissue (sWAT) and the adipogenesis potential of adipose-derived stem cells (ASCs) decrease. It is known that the shortening of cilia length by pro-inflammatory cytokines is related to the decreased adipogenic differentiation of ASCs via increase in Wnt5a/β-catenin. High-intensity focused ultrasound (HIFU) is known to upregulate heat shock proteins (HSP), which decrease levels of pro-inflammatory cytokines. In this study, we evaluated whether HIFU modulates the cilia of ASCs by upregulating HSP70 and decreasing inflammatory cytokines. HIFU was applied at 0.2 J to rat skin, which was harvested at 1, 3, 7, and 28 days. All results for HIFU-applied animals were compared with control animals that were not treated. HIFU increased expression of HSP70 and decreased expression of NF-κB, IL-6, and TNF-α in sWAT. HIFU decreased the expression of cilia disassembly-related factors (AurA and HDAC9) in ASCs. Furthermore, HIFU increased the expression of cilia assembly-related factors (KIF3A and IFT88), decreased that of WNT5A/β-catenin, and increased that of the adipogenesis markers PPARγ and CEBPα in sWAT. HIFU increased the number of adipocytes in the sWAT and the thickness of sWAT. In conclusion, HIFU could selectively increase sWAT levels by modulating the cilia of ASCs and be used for skin rejuvenation.     

Hypoxia Promotes Angiogenic Effect in Extracranial Arteriovenous Malformation Endothelial Cells

Arteriovenous malformation (AVM) is characterized by high-flow blood vessels connecting arteries and veins without capillaries. This disease shows increased angiogenesis and a pathophysiological hypoxic environment in proximal tissues. Here, we analyzed the effects of hypoxia on angiogenesis in the endothelial cells (ECs) of AVM and normal tissues. ECs from human normal and AVM tissues were evaluated using immunocytochemistry with CD31. In vitro tube formation under hypoxia was tested in both ECs using Matrigel. The relative expression of angiogenesis-related genes was measured using real-time PCR. Under normoxia, CD31 was significantly higher in AVM ECs (79.23 ± 0.65%) than in normal ECs (74.15 ± 0.70%). Similar results were observed under hypoxia in AVM ECs (63.85 ± 1.84%) and normal ECs (60.52 ± 0.51%). In the tube formation test under normoxic and hypoxic conditions, the junction count and total vessel length were significantly greater in AVM ECs than normal ECs. Under both normoxia and hypoxia, the angiogenesis-related gene FSTL1 showed a significantly higher expression in AVM ECs than in normal ECs. Under hypoxia, CSPG4 expression was significantly lower in AVM ECs than in normal ECs. Accordingly, the angiogenic effect was increased in AVM ECs compared with that in normal ECs. These results provide a basic knowledge for an AVM treatment strategy.     

Ultra-small PbSe Quantum Dots Synthesis by Chemical Nucleation Controlling

Ultra-small PbSe quantum dots (QDs) were synthesized using conventional hot-injection method.A small amount of Sn was used as a nucleation promotion agent to control nucleation and growth during the QDs synthesis process.The average diameter of the QDs is about 1.6 nm,of which absorption peak centers at 550 nm and photoluminescence peak centers at 750 nm under 350 nm laser excitation with power as low as 500 μW.Transmission electron microscopy images confirm that the QDs size well matches with t...     

设置垫板的形件螺栓连接滞回性能试验研究

该文综述了对称和非对称型摩擦耗能连接40多年以来的发展历史和研究现状。摩擦耗能连接可用于结构的减震耗能,通过合理设计可实现地震作用下带摩擦耗能连接结构的低损伤,提高结构的韧性。研发滞回性能稳定、重复性好的摩擦耗能连接是相关研究的主要目标之一。该文从微观和宏观两个方面介绍了金属滑移面之间的摩擦磨损机理,从摩擦磨损的角度讨论了不同摩擦片材料对摩擦连接减震性能的影响。描述了螺栓预紧力大小对摩擦连接减震性能的影响,也总结了摩擦连接的抗腐蚀和抗火性能。阐述了摩擦耗能连接在钢结构支撑、梁柱节点和柱脚节点的应用,并介绍了相关节点的设计方法。对此类连接的关键技术进行了总结,并对该技术的后续研究进行了展望。     

Correction to: A note on the three methods of item analysis

Behaviormetrika - In the original publication of the article, Appendix A was published incorrectly.