Cholesterol lowering effect of a soy drink enriched with plant sterols in a French population with moderate hypercholesterolemia

<p>Abstract</p> <p>Background</p> <p>Plant sterols are an established non-pharmacological means to reduce total and LDL blood cholesterol concentrations and are therefore recommended for cholesterol management by worldwide-renown health care institutions. Their efficacy has been proven in many types of foods with the majority of trials conducted in spreads or dairy products. As an alternative to dairy products, soy based foods are common throughout the world. Yet, there is little evidence supporting the efficacy of plant sterols in soy-based foods. The objective of this study was to investigate the effect of a soy drink enriched with plant sterols on blood lipid profiles in moderately hypercholesterolemic subjects.</p> <p>Methods</p> <p>In a randomized, placebo-controlled double-blind mono-centric study, 50 subjects were assigned to 200 ml of soy drink either enriched with 2.6 g plant sterol esters (1.6 g/d free plant sterol equivalents) or without plant sterols (control) for 8 weeks. Subjects were instructed to maintain stable diet pattern and physical activity. Plasma concentrations of lipids were measured at initial visit, after 4 weeks and after 8 weeks. The primary measurement was the change in LDL cholesterol (LDL-C). Secondary measurements were changes in total cholesterol (TC), non-HDL cholesterol (non-HDL-C), HDL cholesterol (HDL-C) and triglycerides.</p> <p>Results</p> <p>Regular consumption of the soy drink enriched with plant sterols for 8 weeks significantly reduced LDL- C by 0.29 mmol/l or 7% compared to baseline (p < 0.05). TC and non-HDL-C concentrations decreased by 0.26 mmol/l and 0.31 mmol/l (each p < 0.05), respectively. Mean reductions in total, LDL and non-HDL cholesterol were significantly greater than in the placebo group (p < 0.05). HDL-C and triglycerides were not affected. Compliance was very high (>96%), and products were well tolerated.</p> <p>Conclusion</p> <p>Daily consumption of a plant sterol-enriched soy drink significantly decreased total, non-HDL and LDL cholesterol and is therefore an interesting and convenient aid in managing mild to moderate hypercholesterolemia.</p

Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease

Peer reviewedPublisher PD

Osteoprogenitor SFRP1 prevents exhaustion of hematopoietic stem cells via PP2A-PR72/130-mediated regulation of p300

Remodeling of the bone marrow microenvironment in chronic inflammation and in aging reduces hematopoietic stem cell (HSC) function. To assess the mechanisms of this functional decline of HSC and find strategies to counteract it, we established a model in which the Sfrp1 gene was deleted in Osterix+ osteolineage cells (OS1Δ/Δ mice). HSC from these mice showed severely diminished repopulating activity with associated DNA damage, enriched expression of the reactive oxygen species pathway and reduced single-cell proliferation. Interestingly, not only was the protein level of Catenin beta-1 (bcatenin) elevated, but so was its association with the phosphorylated co-activator p300 in the nucleus. Since these two proteins play a key role in promotion of differentiation and senescence, we inhibited in vivo phosphorylation of p300 through PP2A-PR72/130 by administration of IQ-1 in OS1Δ/Δ mice. This treatment not only reduced the b-catenin/phosphop300 association, but also decreased nuclear p300. More importantly, in vivo IQ-1 treatment fully restored HSC repopulating activity of the OS1Δ/Δ mice. Our findings show that the osteoprogenitor Sfrp1 is essential for maintaining HSC function. Furthermore, pharmacological downregulation of the nuclear b-catenin/phospho-p300 association is a new strategy to restore poor HSC function

In-depth LCCC-(GELC)-SEC characterization of ABA block copolymers generated by a mechanistic switch from RAFT to ROP

A recently introduced procedure involving a mechanistic switch from reversible addition-fragmentation chain transfer (RAFT) polymerization to ring-opening polymerization (ROP) to form diblock copolymers is applied to synthesize ABA (star) block copolymers. The synthetic steps include the polymerization of styrene with R-group designed RAFT agents, the transformation of the thiocarbonyl thio end groups into OH functionalities, and their subsequent chain extension by ROP. The obtained linear ABA poly(ε- caprolactone)-block-poly(styrene)-block-poly(ε-caprolactone) (pCL-b-pS-b-pCL) (12 500 g mol -1 ≤ M n ≤ 33 000 g mol -1) and the star-shaped poly(styrene)-block-poly(ε- caprolactone) (M n = 36 000 g mol -1) copolymers were analyzed by size exclusion chromatography (SEC), nuclear magnetic resonance (NMR), infrared (IR) spectroscopy, and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. The focus of the current study is on the detailed characterization of the ABA (star) block polymers via multidimensional chromatographic techniques specifically high performance liquid chromatography coupled to size exclusion chromatography (HPLC-SEC). In particular, we demonstrate the first time separation of poly(ε- caprolactone) (pCL) homopolymer and additionally poly(styrene) (pS) from the ABA poly(ε-caprolactone)-b-poly(styrene)-b-poly(ε-caprolactone) and star-shaped poly(styrene)-b-poly(ε-caprolactone) block copolymer utilizing critical conditions (CC) for pCL with concomitant gradient elution liquid chromatography (GELC). © 2011 American Chemical Society

Development of an Artificial 3D Liver Phantom for Analysis of Radiotherapeutic Effects In Vitro

Over recent decades, stereotactic body radiotherapy has garnered increasing popularity. Unfortunately, conventional preclinical 2D in vitro models are often insufficient for studying radiotherapy effects. Therefore, in this study, we developed a novel anthropomorphic in vitro liver phantom, which simulates the relevant hepatocellular carcinoma (HCC) tumor microenvironment and spatial organization. The liver phantom was 3D printed, filled with tissue-mimicking agarose mixture, and designed to fit ten microfluidic chips (MCs), in which HepG2 cells were seeded. Airtight MCs induced hypoxic conditions, as verified by Hif1α staining. Irradiation was conducted with 20 Gy in one fraction using a CyberKnife, in either a 2D setup, or by irradiating MCs arranged in the 3D-printed liver model using an individually calculated treatment plan. Post-irradiation cellular damage was determined via γH2AX staining. Here, we demonstrate a new physiologically relevant approach to model HCC pathology following radiotherapy. Comparing γH2AX staining in normoxic conditions to cells grown in MCs (hypoxic conditions) revealed a reduction in cellular damage of 30.24% (p = 0.0001) in the hypoxic environment. Moreover, we compared the scattering effect of radiation on a conventional 2D in vitro model to our new 3D anthropomorphic liver phantom and observed a significant γH2AX intensity reduction of 9.6% (p = 0.0294) in HepG2 cells irradiated in the phantom. Our approach of utilizing a liver phantom takes into account the hypoxic tumor microenvironment and 3D scattering effects of tissue irradiation, thereby modeling both physical and biological parameters of HCC tumors. The use of tissue phantoms lays the groundwork for future examination of other hypoxic tumors and offers a more comprehensive approach for screening and analysis of novel cancer therapeutics

Development of an Artificial 3D Liver Phantom for Analysis of Radiotherapeutic Effects In Vitro

Over recent decades, stereotactic body radiotherapy has garnered increasing popularity. Unfortunately, conventional preclinical 2D in vitro models are often insufficient for studying radiotherapy effects. Therefore, in this study, we developed a novel anthropomorphic in vitro liver phantom, which simulates the relevant hepatocellular carcinoma (HCC) tumor microenvironment and spatial organization. The liver phantom was 3D printed, filled with tissue-mimicking agarose mixture, and designed to fit ten microfluidic chips (MCs), in which HepG2 cells were seeded. Airtight MCs induced hypoxic conditions, as verified by Hif1&alpha; staining. Irradiation was conducted with 20 Gy in one fraction using a CyberKnife, in either a 2D setup, or by irradiating MCs arranged in the 3D-printed liver model using an individually calculated treatment plan. Post-irradiation cellular damage was determined via &gamma;H2AX staining. Here, we demonstrate a new physiologically relevant approach to model HCC pathology following radiotherapy. Comparing &gamma;H2AX staining in normoxic conditions to cells grown in MCs (hypoxic conditions) revealed a reduction in cellular damage of 30.24% (p = 0.0001) in the hypoxic environment. Moreover, we compared the scattering effect of radiation on a conventional 2D in vitro model to our new 3D anthropomorphic liver phantom and observed a significant &gamma;H2AX intensity reduction of 9.6% (p = 0.0294) in HepG2 cells irradiated in the phantom. Our approach of utilizing a liver phantom takes into account the hypoxic tumor microenvironment and 3D scattering effects of tissue irradiation, thereby modeling both physical and biological parameters of HCC tumors. The use of tissue phantoms lays the groundwork for future examination of other hypoxic tumors and offers a more comprehensive approach for screening and analysis of novel cancer therapeutics

Very High Cycle Fatigue Investigations on the Fatigue Strength of Additive Manufactured and Conventionally Wrought Inconel 718 at 873 K

The fatigue lives of additively manufactured (AM) Inconel 718 (IN718) produced by selective electron beam melting and conventional wrought material as reference conditions were studied in the very high cycle fatigue regime under fully reversed loading (R = −1) at the elevated temperature of 873 K using an ultrasonic fatigue testing system. The fatigue lives of the AM material were significantly reduced compared to the wrought material, which is discussed in relation to the microstructure and a fractographical analysis. The additively manufactured material showed large columnar grains with a favoured orientation to the building direction and porosity, whereas the wrought material showed a fine-grained structure with no significant texture, but had Nb- and Ti-rich non-metallic inclusions. Crystallographic crack initiation as well as crack initiation from the surface or internal defects were observed for the AM and the wrought IN718, respectively

In-Depth LCCC-(GELC)-SEC Characterization of ABA Block Copolymers Generated by a Mechanistic Switch from RAFT to ROP

A recently introduced procedure involving a mechanistic switch from reversible addition–fragmentation chain transfer (RAFT) polymerization to ring-opening polymerization (ROP) to form diblock copolymers is applied to synthesize ABA (star) block copolymers. The synthetic steps include the polymerization of styrene with R-group designed RAFT agents, the transformation of the thiocarbonyl thio end groups into OH functionalities, and their subsequent chain extension by ROP. The obtained linear ABA poly­(ε-caprolactone)-<i>block</i>-poly­(styrene)-<i>block</i>-poly­(ε-caprolactone) (pCL-<i>b</i>-pS-<i>b</i>-pCL) (12 500 g mol^–1 ≤ <i>M</i>_n ≤ 33 000 g mol^–1) and the star-shaped poly­(styrene)-<i>block</i>-poly­(ε-caprolactone) (<i>M</i>_n = 36 000 g mol^–1) copolymers were analyzed by size exclusion chromatography (SEC), nuclear magnetic resonance (NMR), infrared (IR) spectroscopy, and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. The focus of the current study is on the detailed characterization of the ABA (star) block polymers via multidimensional chromatographic techniques specifically high performance liquid chromatography coupled to size exclusion chromatography (HPLC-SEC). In particular, we demonstrate the first time separation of poly­(ε-caprolactone) (pCL) homopolymer and additionally poly­(styrene) (pS) from the ABA poly­(ε-caprolactone)-<i>b</i>-poly­(styrene)-<i>b</i>-poly­(ε-caprolactone) and star-shaped poly­(styrene)-<i>b</i>-poly­(ε-caprolactone) block copolymer utilizing critical conditions (CC) for pCL with concomitant gradient elution liquid chromatography (GELC)