Inhibition of the FGF/FGFR System Induces Apoptosis in Lung Cancer Cells via c-Myc Downregulation and Oxidative Stress

Lung cancer represents an extremely diffused neoplastic disorder with different histological/molecular features. Among the different lung tumors, non-small-cell lung cancer (NSCLC) is the most represented histotype, characterized by various molecular markers, including the expression/overexpression of the fibroblast growth factor receptor-1 (FGFR1). Thus, FGF/FGFR blockade by tyrosine kinase inhibitors (TKi) or FGF-ligand inhibitors may represent a promising therapeutic approach in lung cancers. In this study we demonstrate the potential therapeutic benefit of targeting the FGF/FGFR system in FGF-dependent lung tumor cells using FGF trapping (NSC12) or TKi (erdafitinib) approaches. The results show that inhibition of FGF/FGFR by NSC12 or erdafitinib induces apoptosis in FGF-dependent human squamous cell carcinoma NCI-H1581 and NCI-H520 cells. Induction of oxidative stress is the main mechanism responsible for the therapeutic/pro-apoptotic effect exerted by both NSC12 and erdafitinib, with apoptosis being abolished by antioxidant treatments. Finally, reduction of c-Myc protein levels appears to strictly determine the onset of oxidative stress and the therapeutic response to FGF/FGFR inhibition, indicating c-Myc as a key downstream effector of FGF/FGFR signaling in FGF-dependent lung cancers.     

江森自控亚太总部

正位于上海的江森自控亚太总部是创新设计、可持续性和智能科技的领先典范。晋思建筑事务所上海和芝加哥办公室与拥有领先建筑技术和解决方案的江森自控携手合作,创建了世界级的总部大楼和企业园区,最大限度地减少了对自然环境的影响,增强了建筑的美观度与功能性,力求达到最高水平的入住舒适度。由于其前瞻性设计、智能节能解决方案以及对可持续发展承诺,该总部赢得了国际金融公司-世界银行集团     

Pro-Resolving Lipid Mediator Resolvin E1 Mitigates the Progress of Diethylnitrosamine-Induced Liver Fibrosis in Sprague-Dawley Rats by Attenuating Fibrogenesis and Restricting Proliferation

Liver fibrosis is a complex process associated to most types of chronic liver disease, which is characterized by a disturbance of hepatic tissue architecture and the excessive accumulation of extracellular matrix. Resolvin E1 (RvE1) is a representative member of the eicosapentaenoic omega-3 lipid derivatives, and is a drug candidate of the growing family of endogenous resolvins. Considering the aforementioned, the main objective of this study was to analyze the hepatoprotective effect of RvE1 in a rat model of liver fibrosis. Male Sprague-Dawley rats received diethylnitrosamine (DEN, 70 mg/mg body weight intraperitoneally (i.p)) as an inductor of liver fibrosis once weekly and RvE1(100 ng/body weight i.p) twice weekly for four weeks. RvE1 suppressed the alterations induced by DEN, normalizing the levels of alanine aminotransferase (ALT), albumin, and lactate dehydrogenase (LDH), and ameliorated DEN injury by decreasing the architecture distortion, inflammatory infiltration, necrotic areas, and microsteatosis. RvE1 also limited DEN-induced proliferation through a decrease in Ki67-positive cells and cyclin D1 protein expression, which is related to an increase of the levels of cleaved caspase-3. Interestingly, we found that RvE1 promotes higher nuclear translocation of nuclear factor κB (NF-κB)p65 than DEN. RvE1 also increased the levels of nuclear the nuclear factor erythroid 2–related factor 2 (Nrf2), but with no antioxidant effect, measured as an increase in glutathione disulfide (GSSG) and a decrease in the ratio of glutathione (GSH)/GSSG. Taken together, these results suggest that RvE1 modulates the fibrogenesis, steatosis, and cell proliferation in a model of DEN induced fibrosis.     

A tale of two Great Lakes conferences: Urging global collaboration on our largest freshwater resources

Scientific meetings and conferences are a part of the scientific process, and can facilitate collaboration, idea-sharing, and harmonization of research and management. The success of a conference can be measured using many criteria, including consistency and reoccurrence of the meetings, credibility by participation of reputable professionals, and attendance by a diverse community. In the interest of increasing the success of large-lake, freshwater science, policy, and management, this comment focuses on two recent conferences attended by the authors: the 60th annual meeting of the International Association for Great Lakes Research, in Detroit, U.S.A., and the African Great Lakes Conference, in Entebbe, Uganda. By our measures of success, we suggest that to make a larger impact on research, policy, and management of global, large, freshwater lakes that each conference can improve, either through greater diversity of experts from the global freshwater research community, or by consistently reoccurring on a regular basis.     

Relative contributions of nearshore and wetland habitats to coastal food webs in the Great Lakes

Hydrologic linkages among coastal wetland and nearshore areas allow coastal fish to move among the habitats, which has led to a variety of habitat use patterns. We determined nutritional support of coastal fishes from 12 wetland-nearshore habitat pairs using stable isotope analyses, which revealed differences among species and systems in multi-habitat use. Substantial (proportions?>?0.30) nutrition often came from the habitat other than that in which fish were captured. Nearshore subsidies to coastal wetlands indicate wetlands are not exclusively exporters of energy and materials; rather, there is reciprocity in the mutual energetic support of nearshore and wetland food webs. Coastal wetland hydrogeomorphology influenced the amount of multi-habitat use by coastal fishes. Fishes from systems with relatively open interfaces between wetland and nearshore habitats exhibited less nutritional reliance on the habitat in which they were captured, and higher use of resources from the adjacent habitat. Comparisons of stable isotope analyses of nutrition with otolith analyses of occupancy indicated nutritional sources often corresponded with habitat occupancy; however, disparities among place of capture, otolith analyses, and nutritional analyses indicated differences in the types of support those analyses inform. Disparities between occupancy information and nutritional information can stem from movements for support functions other than foraging. Together, occupancy information from otolith microchemistry and nutritional information from stable isotope analyses provide complementary measures of the use of multiple habitats by mobile consumers. This work underscores the importance of protecting or restoring a diversity of coastal habitats and the hydrologic linkages among them.     

Development of a difunctional oxirane and multifunctional acrylate interpenetrating polymer network composite system with antimicrobial properties

This research continued the development of a difunctional Oxirane and multifunctional Acrylate interpenetrating polymer network composite System (OASys) with antimicrobial properties. The effects of 4-Isopropyl-4′-methyldiphenyliodonium tetrakis (pentafluorophenyl) borate (Borate), hexamethylene diamine (HMDA) and N,N-dimethyl p-toluidine (DMPT) on OASys (Epalloy 5001:dipentaerythritol hexaacrylate) composite hardness, contact angle, monomer-to-polymer degree of conversion (DoC), mechanical properties, polymerization shrinkage, shrinkage stress, and antimicrobial properties were determined. Bis-GMA:TEGDMA composites were used as the control. OASys composites with 9 wt% Borate and 0.5 wt% DMPT or 1.5 wt% HMDA had comparable hardness, DoC's and polymerization shrinkages to controls, but had lower contact angles and mechanical properties. Additionally, OASys composites with 1.5 wt% HMDA had significantly less polymerization stress than controls and demonstrated significant antibacterial activity against Streptococcus mutans and Lactobacillus casei out to 3 months. With lower shrinkage stress and long-term antimicrobial activity, OASys composites look promising for increasing the clinical lifetime of dental composites, but improvements in mechanical properties are needed.     

Electrospun microporous gelatin–polycaprolactone blend tubular scaffold as a potential vascular biomaterial

The work reported involved the fabrication of an electrospun tubular conduit of a gelatin and polycaprolactone (PCL) blend as an adventitia‐equivalent construct. Gelatin was included as the matrix for increased biocompatibility with the addition of PCL for durability. This is contrary to most of the literature available for biomaterials based on blends of gelatin and PCL where PCL is the major matrix. The work includes the assiduous selection of key electrospinning parameters to obtain smooth bead‐free fibres with a narrow distribution of pore size and fibre diameter. Few reports elucidate the optimization of all electrospinning parameters to fabricate tubular conduits with a focus on obtaining homogeneous pores and fibres. This stepwise investigation would be unique for the fabrication of gelatin–PCL electrospun tubular constructs. The fabricated microfibrous gelatin–PCL constructs had pores of size ca 50–100 μm reportedly conducive for cell infiltration. The measured value of surface roughness of 57.99 ± 17.4 nm is reported to be favourable for protein adhesion and cell adhesion. The elastic modulus was observed to be similar to that of the tunica adventitia of the native artery. Preliminary in vitro and in vivo biocompatibility tests suggest safe applicability as a biomaterial. Minimal cytotoxicity was observed using MTT assay. Subcutaneous implantation of the scaffold demonstrated acute inflammation which decreased by day 15. The findings of this study could enable the fabrication of smooth bead‐free microfibrous gelatin–PCL tubular construct as viable biomaterial which can be included in a bilayer or a trilayer scaffold for vascular tissue engineering. © 2019 Society of Chemical Industry     

Characterization of Extra Virgin Olive Oil from Southern Brazil

Six olive oils extracted from the cultivars Arbequina, Arbosana, Coratina, Frantoio, Koroneiki, and Picual from 2017 and 2018 harvests, cultivated in Pinheiro Machado, Rio Grande do Sul, Brazil, are evaluated for standard oil composition parameters and bioactive constituents (pigments, tocopherols, and phenolic compounds). Multivariate principal component analysis (PCA) and univariate ANOVA and Fisher's LSD test are used to verify the effect of cultivar and harvest year on oil composition. Olive oil composition met extra virgin olive oil (EVOO) standard parameters and is influenced by both cultivar and harvest year. EVOO produced in 2018 has greater chlorophyll, caffeic acid, ligstroside aglycone, hydroxyoleuropein aglycone, syringic acid, and hydroxytyrosol acetate contents than the EVOOs from 2017. Linoleic acid, ferulic acid, ligstroside aglycone, and hydroxytyrosol acetate are the variables whose contents most contributed to the differentiation of oils by cultivar in both harvest years. Chemical characterization analyses allow for the differentiation of oil composition based on harvest year and cultivar. Metabolic quality data obtained here support the establishment of a local EVOO profile and the compounds that most contributed to treatment differentiation may serve as markers that can be utilized in determining origin, cultivar, and harvest year. Practical Applications: Olive production in Brazil is recent and is based on European cultivars which have not been bred for the local environmental conditions. Therefore, the measurement of olive oil metabolic quality will determine cultivar adaptability to local edaphoclimatic conditions as well as assist in the establishment of a standard of identity for the product and promote the development of its market. Olive oil produced in Southern Brazil shows high quality, and is especially rich in phenolic compounds. Although harvest year influences oil composition, oil from both harvests meet EVOO standards and cultivar specific metabolic markers are observed. This study provides the foundation for olive producers in Southern Brazil to seek authentication of the geographical origin of olive oil.