Circular Sponge against miR-21 Enhances the Antitumor Activity of Doxorubicin against Breast Cancer Cells

Breast cancer is the most common type of cancer in women, with chemotherapy being the main strategy. However, its effectiveness is reduced by drug resistance mechanisms. miR-21 is upregulated in breast cancer that has been linked to drug resistance and carcinogenic processes. Our aim was to capture miR-21 with a circular sponge (Circ-21) and thus inhibit the carcinogenic processes and drug resistance mechanisms in which it participates. Proliferation, migration, colony formation, cell cycle, and poly [ADP-ribose] polymerase 1 (PARP-1) and vascular endothelial growth factor (VEGF) detection assays were performed with MCF7 breast cancer cells and MCF10A non-tumor cells. In addition, doxorubicin resistance tests and detection of drug resistance gene expression were performed in MCF7 cells. Reduction in proliferation, as well as migration and colony formation, increased PARP-1 expression, inhibition of VEGF expression and cell cycle arrest in G2/M phase were displayed in the Circ-21 MCF7, which were not observed in the MCF10A cells. Furthermore, in the MCF7 cells, the Circ-21 enhanced the antitumor activity of doxorubicin and decreased the expression of resistance genes: ABCA1, ABCC4, and ABCC5. Based on these results, the use of Circ-21 can be considered a first step for the establishment of an effective gene therapy in the treatment of breast cancer.     

River fragmentation in the northern Sandomierz Basin (SE Poland)

River fragmentation is a process highly detrimental for fish survival by impeding their migrations. Although fragmentation by big dams has been studied, there is still a big deficiency of data related to small barriers. This study was designed as a detailed, local-scale analysis of several chosen river stretches in the Sandomierz Basin, Poland. It aimed to: (1) map all natural and artificial barriers in the study area, (2) assess the impacts of these barriers on fish migration, (3) compare findings to existing databases, and (4) make recommendations for improved barrier management. Ten lowland rivers covering a total 424 km length were surveyed by river walkovers and kayak surveys, with all the barriers mapped and all the artificial structures assessed for fish migration using the ICE protocol protocol for ecological continuity. There were 67 beaver dams and 89 artificial barriers recorded, with only 24% of the latter being included in national databases. The average artificial barrier density in all the surveyed rivers was 0.2 barriers/km and varied from 0.75 barriers/km in first order streams to 0.01 barriers/km in sixth order river. The findings revealed that 18% of the barriers were passable for all fish species, with 35% totally impassable. The analysis of specific barrier parameters indicated that water depth at the barrier had a greater influence on fish passability than the barrier height. Several barriers were proposed for removal to specifically improve the potential for fish migration.     

Guest editorial for the theme section on modeling language engineering

Software and Systems Modeling -     

Engineering of a Plant Isoprenyl Diphosphate Synthase for Development of Irregular Coupling Activity

We performed mutagenesis on a regular isoprenyl diphosphate synthase (IDS), neryl diphosphate synthase from Solanum lycopersicum (SlNPPS), that has a structurally related analogue performing non-head-to-tail coupling of two dimethylallyl diphosphate (DMAPP) units, lavandulyl diphosphate synthase from Lavandula x intermedia (LiLPPS). Wild-type SlNPPS catalyses regular coupling of isopentenyl diphosphate (IPP) and DMAPP in cis-orientation resulting in the formation of neryl diphosphate. However, if the enzyme is fed with DMAPP only, it is able to catalyse the coupling of two DMAPP units and synthesizes two irregular monoterpene diphosphates; their structures were elucidated by the NMR analysis of their dephosphorylation products. One of the alcohols is lavandulol. The second compound is the trans-isomer of planococcol, the first example of an irregular cyclobutane monoterpene with this stereochemical configuration. The irregular activity of SlNPPS constitutes 0.4 % of its regular activity and is revealed only if the enzyme is supplied with DMAPP in the absence of IPP. The exchange of asparagine 88 for histidine considerably enhanced the non-head-to-tail coupling. While still only observed in the absence of IPP, irregular activity of the mutant reaches 13.1 % of its regular activity. The obtained results prove that regular IDS are promising starting points for protein engineering aiming at the development of irregular activities and leading to novel monoterpene structures.     

结构设计的社会价值——若昂·维拉诺瓦·阿蒂加斯承重结构设计中的人性维度

若昂·维拉诺瓦·阿蒂加斯(1915-1985)[1][2]身为巴西20世纪最具影响力的建筑师之一,其独特的建筑作品最近才受到国际上的广泛关注和认可.阿蒂加斯相信人性内容应寓于形式探索,唯有将之融入结构设计,才能赋予其意义.力倡和平与民主但又政治激进的阿蒂加斯,在自己的设计实践中认知到了将结构升格为社会隐喻的永恒潜力.从...     

Impact of silica pore structure on the performance of metallocene catalysts in ethylene gas-phase polymerization

Several commercial silicas were used to support metallocene active centres, and the resulting precatalysts were used to study the impact of the pore size and pore size distribution of the support on the polymerization kinetics and resulting polymer properties. Pore volume distribution played a major role in the fragmentation of silica-supported catalysts, where mesoporous silicas with a narrow distribution in the region obtained higher activities and faster fragmentation than silicas with a broad pore volume distribution. Therefore, it is shown that care must be taken when using standard information on particle porosity, as this quantity can be misleading. It appears that the minimum pore size, particularly on the particle surface, can be a very important parameter even if it does not impact the estimate of the porosity.     

The Protective Effect of Pumpkin and Fermented Whey Mixture against AFB1 and OTA Immune Toxicity In Vitro. A Transcriptomic Approach

Scope

The aim of the study is to investigate in Jurkat cells the possible beneficial effect of pumpkin (P) and fermented milk whey (FW) mixture against aflatoxin B1 (AFB1) and ochratoxin A (OTA) induced alterations in gene expression profile.

Methods and results

Human T cells are exposed for 7 days to digested bread extracts containing P-FW mixture along with AFB1 and OTA, individually and in combination. The results of RNA sequencing show that AFB1 P-FW exposure resulted in 34 differentially expressed genes (DEGs) while 3450 DEGs are found in OTA P-FW exposure and 3264 DEGs in AFB1-OTA P-FW treatment. Gene ontology analysis reveals biological processes and molecular functions related to immune system and inflammatory response. Moreover, PathVisio analysis points to eicosanoid signaling via lipoxygenase as the main pathway altered by AFB1 P-FW exposure whereas interferon signaling is the most affected pathway after OTA P-FW and AFB1-OTA P-FW treatments.

Conclusions

The mitigation of genes and inherent pathways typically associated with the inflammatory response suggest not only the anti-inflammatory and protective role of P-FW mixture but also their possible application in food industry to counteract AFB1 and OTA toxic effects on human and animal health.     

Synthesis of Cyanoethyl Inulin,Aminopropyl Inulin and Carboxyethyl Inulin

Inulin was cyanoethylated by reaction with acrylonitrile in the presence of aqueous sodium hydroxide. Products with a degree of substution (ds) from 0.2 to 1.6 were prepared. The materials were analyzed using NMR spectroscopy and GPC analysis. The nitrile groups of cyanoethyl inulin were converted into amino groups by reduction with sodium borohydride in the presence of a transition metal chloride (CoCl₂.6H₂O). Furthermore, the nitrile groups were hydrolyzed towards carboxylates using hydrogen peroxide in alkaline medium. The polycarboxylate obtained by this means was shown to possess good calcium carbonate crystallization inhibition properties.     

Improving In Vitro Detection of Sensitization to Lipid Transfer Proteins: A New Molecular Multiplex IgE Assay

Scope

LTP-syndrome is characterized by sensitization (IgE) to multiple non-specific lipid transfer proteins (nsLTPs) with a variable clinical outcome. The treatment is primarily based on offending food avoidance. However, the determination of Pru p 3-specific IgE is currently the main diagnostic tool to assess sensitization to nsLTPs. Herein, the study evaluates improvement of LTP-syndrome diagnosis and clinical management using a new IgE multiplex-immunoblot assay with a high diversity of food nsLTPs.

Methods and results

An EUROLINE-LTP strip with 28 recombinant nsLTPs from 18 allergenic sources is designed. In total the study investigates 38 patients with LTP-syndrome and compares results from the nsLTPs (LTP-strip) with the respective food extracts of Prick-by-prick (PbP) testing. The agreement exceeds 70% for most nsLTPs, e.g., Pru p 3 (100%), Mal d 3 (97%), Pru av 3 (89%), Pha v 3 isoforms (87%/84%), Ara h 9 (82%), Cor a 8 (82%), and Jug r 3 (82%). The functionality and allergenic relevance of nine recombinant nsLTPs are proven by Basophil activation testing (BAT).

Conclusions

The new IgE multiplex-immunoblot nsLTP assay shows a good diagnostic performance allowing culprit food assessment. Negative results from LTP-strip may indicate potentially tolerable foods, improving diet intervention and patients’ quality of life.