Raw dataset of compression tests on a vegetable oil-based polyurethane foam exposed to different ageing conditions.

The current dataset brings raw compression test information of a vegetable-based polyurethane foam (PUF) exposed to different temperatures over different periods of time. Such experimental dataset can provide researchers with important information in the application of numerical and data-driven simulations. Also, it saves money and time once the experimental part is already available. At total, 90 compression tests were done following the ASTM D1621-16 standard with pictures for digital image correlation (DIC) being simultaneously acquired. The 90 specimens were divided in nine different ageing conditions. The foam was considered transversely isotropic, thus, 10 specimens for each condition were divided in two groups, five specimens for direction 1 and five for direction 3, where direction 3 is the foam expansion direction. The 3D DIC results show longitudinal and transverse strains from virtual extensometers. The results are available in .TRA and .csv files for the tests and DIC outputs, respectively. Also, the dataset brings the pictures used for DIC in .TIF format. It also brings the dimensions of each specimen prior to the test in .txt format. These results provide information for the calculation of major mechanical properties that can be freely used in finite element models for different and creative ways to simulate the ageing process of a vegetable-based PUF.

Numerical Approach to Simulate the Mechanical Behavior of Biodegradable Polymers during Erosion.

Biodegradable polymers find applications in many market segments. The ability to meet mechanical requirements within a certain time range, after which it degrades and is naturally absorbed, can be used to produce short-term use products that can be easily disposable with less environmental impact. In the segment of medical devices used in regenerative medicine, these materials are used to produce temporary implants that are naturally assimilated by the human body, avoiding a removal surgery. However, the design of these temporary devices still presents great challenges, namely in the verification of the main requirement: the lifetime of the device, associated with the progressive loss of mechanical properties, until its complete erosion and assimilation. Thus, in this study, a numerical approach is proposed to simulate the polymeric device's mechanical behavior during its hydrolytic degradation by combining the hydrolysis kinetics, that depends on mechanical factors and promotes a decrease of molecular weight and consequent decrease of mechanical performance, and erosion, when molecular weight reaches a threshold value and the polymer becomes soluble and diffuses outward, resulting in mass loss and decreasing cross-sectional area, which also contributes to the mechanical performance reduction of the device. A phenomenological approach, using the combination of continuum-based hydrolytic damage for the evolution of mechanical properties that depends on the stress field and further removal of the degraded element (to simulate mass loss) was used. Both elastoplastic and hyperelastic constitutive models were applied on this study, where the material model parameters locally depend on the molecular weight.

Accelerated Aging on the Compression Properties of a Green Polyurethane Foam: Experimental and Numerical Analysis.

The aim of this work is to evaluate the changes in compression properties of a bio-based polyurethane foam after exposure to 90 °C for different periods of time, and to propose a method to extrapolate these results and use a numerical approach to predict the compression behaviour after degradation for untested conditions at different degradation times and temperatures. Bio-based polymers are an important sustainable alternative to oil-based materials. This is explained by the foaming process and the density along the material as it was possible to see in a digital image correlation analysis. After 60 days, stiffness was approximately decreased by half in both directions. The decrease in yield stress due to thermo-oxidative degradation had a minor effect in the foaming directions, changing from 352 kPa to 220 kPa after 60 days, and the transverse property was harshly impacted changing from 530 kPa to 265 kPa. The energy absorption efficiency was slightly affected by degradation. The simulation of the compression stress-strain curves were in accordance to the experimental data and made it possible to predict the changes in mechanical properties for intermediate periods of degradation time. The plateau stress for the unaged foam transverse to the foaming direction presented experimental and numerical values of 450 kPa and 470 kPa, respectively. In addition, the plateau stresses in specimens degraded for 40 days present very similar experimental and numerical results in the same direction, at 310 kPa and 300 kPa, respectively. Therefore, this paper presents important information regarding the life-span and degradation of a green PUF. It provides insights into how compression properties vary along degradation time as function of material operation temperature, according to the Arrhenius degradation equation.

Exportin 1-mediated nuclear/cytoplasmic trafficking controls drug sensitivity of classical Hodgkin's lymphoma.

Exportin 1 (XPO1) is the main nuclear export receptor that controls the subcellular trafficking and the functions of major regulatory proteins. XPO1 is overexpressed in various cancers and small inhibitors of nuclear export (SINEs) have been developed to inhibit XPO1. In primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin's lymphoma (cHL), the XPO1 gene may be mutated on one nucleotide and encodes the mutant XPO1E571K . To understand the impact of mutation on protein function, we studied the response of PMBL and cHL cells to selinexor, a SINE, and ibrutinib, an inhibitor of Bruton tyrosine kinase. XPO1 mutation renders lymphoma cells more sensitive to selinexor due to a faster degradation of mutant XPO1 compared to the wild-type. We further showed that a mistrafficking of p65 (RELA) and p52 (NFκB2) transcription factors between the nuclear and cytoplasmic compartments accounts for the response toward ibrutinib. XPO1 mutation may be envisaged as a biomarker of the response of PMBL and cHL cells and other B-cell hemopathies to SINEs and drugs that target even indirectly the NFκB signaling pathway.

Calorie Restriction and SIRT1 Overexpression Induce Different Gene Expression Profiles in White Adipose Tissue in Association with Metabolic Improvement.

INTRODUCTION: Calorie restriction (CR) exerts multiple effects on health, including the amelioration of systemic insulin resistance. Although the precise mechanisms by which CR improves glucose homeostasis remain poorly defined, SIRT1 has been suggested to act as a central mediator of the cellular responses to CR. Here, we aim at identifying the mechanisms by which CR and SIRT1 modulate white adipose tissue (WAT) function, a key tissue in the control of glucose homeostasis. MATERIAL AND METHODS: A gene expression profiling study using DNA microarrays is conducted in WAT of control and SIRT1 transgenic mice fed ad libitum (AL) and mice subjected to 40% CR. RESULTS: Gene expression profiling reveals a relatively low degree of overlap between the transcriptional programs regulated by SIRT1 and CR. Gene networks related to extracellular matrix appear commonly downregulated by SIRT1/CR, whereas mitochondrial biogenesis is enhanced exclusively by CR. Moreover, WAT inflammation is reduced by CR and SIRT1, although their anti-inflammatory effects appeared to be achieved by regulating different gene networks related to the immune system. CONCLUDING REMARKS: In WAT, SIRT1 does not mediate most of the effects of CR on gene expression. Still, gene networks differentially regulated by SIRT1 and CR converge to reduce WAT inflammation.

Diacerein treatment prevents colitis-associated cancer in mice.

BACKGROUND: Inflammation is a well-established enabling factor for cancer development and provides a framework for the high prevalence of colon cancer in inflammatory bowel disease. In accordance, chronic inflammation has recently been implicated in the development of cancer stem cells (CSCs). However, the mechanism whereby anti-inflammatory drugs act in the prevention of colitis-associated cancer (CAC) is only partially understood. AIM: To evaluate the role of diacerein (DAR), an anti-inflammatory drug that mainly acts through the inhibition of interleukin (IL)-1ß expression in the development of CSCs and CAC. METHODS: The effects of DAR on colon inflammation in mice with CAC were evaluated by inflammatory index, reverse real-time transcription polymerase chain reaction and western blot. Cytokine levels were measured by enzyme-linked immunosorbent assay. Cells assays evaluated the effects of DAR on CSCs. Immunohistochemistry and apoptosis assays were also used to evaluate the effects of DAR on tumorigenesis associated with inflammation. RESULTS: DAR treatment reduced colon inflammation as well as the number and size of tumors in azoxymethane plus dextran sulphate sodium-treated animals. Accordingly, DAR treatment was associated with reduced intracellular signals of inflammation (inhibitor of nuclear factor kappa B kinase and c-Jun N-terminal kinase phosphorylation) in the colon. In addition, DAR treatment was associated with a decrease in colon CSC formation, suggesting that besides reducing colonic inflammation, DAR has a direct effect on the inhibition of colon carcinogenesis. CONCLUSION: Together, these data indicate that DAR-mediated IL-1ß suppression attenuates inflammation-induced colon cancer and CSC formation, highlighting DAR as a potential candidate for the chemoprevention of CAC.

Recent Advances in the Targeting of Epigenetic Regulators in B-Cell Non-Hodgkin Lymphoma.

In the last 10 years, major advances have been made in the diagnosis and development of selective therapies for several blood cancers, including B-cell non-Hodgkin lymphoma (B-NHL), a heterogeneous group of malignancies arising from the mature B lymphocyte compartment. However, most of these entities remain incurable and current treatments are associated with variable efficacy, several adverse events, and frequent relapses. Thus, new diagnostic paradigms and novel therapeutic options are required to improve the prognosis of patients with B-NHL. With the recent deciphering of the mutational landscapes of B-cell disorders by high-throughput sequencing, it came out that different epigenetic deregulations might drive and/or promote B lymphomagenesis. Consistently, over the last decade, numerous epigenetic drugs (or epidrugs) have emerged in the clinical management of B-NHL patients. In this review, we will present an overview of the most relevant epidrugs tested and/or used so far for the treatment of different subtypes of B-NHL, from first-generation epigenetic therapies like histone acetyl transferases (HDACs) or DNA-methyl transferases (DNMTs) inhibitors to new agents showing selectivity for proteins that are mutated, translocated, and/or overexpressed in these diseases, including EZH2, BET, and PRMT. We will dissect the mechanisms of action of these epigenetic inhibitors, as well as the molecular processes underlying their lack of efficacy in refractory patients. This review will also provide a summary of the latest strategies being employed in preclinical and clinical settings, and will point out the most promising lines of investigation in the field.

Pharmacological Targeting of BET Bromodomain Proteins in Acute Myeloid Leukemia and Malignant Lymphomas: From Molecular Characterization to Clinical Applications.

Alterations in protein-protein and DNA-protein interactions and abnormal chromatin remodeling are a major cause of uncontrolled gene transcription and constitutive activation of critical signaling pathways in cancer cells. Multiple epigenetic regulators are known to be deregulated in several hematologic neoplasms, by somatic mutation, amplification, or deletion, allowing the identification of specific epigenetic signatures, but at the same time providing new therapeutic opportunities. While these vulnerabilities have been traditionally addressed by hypomethylating agents or histone deacetylase inhibitors, pharmacological targeting of bromodomain-containing proteins has recently emerged as a promising approach in a number of lymphoid and myeloid malignancies. Indeed, preclinical and clinical studies highlight the relevance of targeting the bromodomain and extra-terminal (BET) family as an efficient strategy of target transcription irrespective of the presence of epigenetic mutations. Here we will summarize the main advances achieved in the last decade regarding the preclinical and clinical evaluation of BET bromodomain inhibitors in hematologic cancers, either as monotherapies or in combinations with standard and/or experimental agents. A mention will finally be given to the new concept of the protein degrader, and the perspective it holds for the design of bromodomain-based therapies.

Epigenetic Mechanisms of ATM Activation after Helicobacter pylori Infection.

Gastric cancer (GC) is the second leading cause of cancer-related mortality worldwide. The disease develops from the accumulation of several genetic and epigenetic changes. Among other risk factors, Helicobacter pylori infection is considered the main driving factor of GC development. H. pylori infection increases DNA damage levels and leads to epigenetic dysregulation, which may favor gastric carcinogenesis. An early step in double-strand break repair is the recruitment of ataxia-telangiectasia mutated serine/threonine kinase (ATM) to the damaged site, where it plays a key role in advancing the DNA damage checkpoint process. H. pylori infection has been associated with the introduction of double-strand breaks in epithelial cells, triggering damage signaling and repair response involving ATM. Thus, the current study analyzed the effect of H. pylori infection on the DNA damage response sensor, ATM, in gastric epithelial cells and in biopsy specimens from patients with GC. In this study, we identified that H. pylori infection stimulated DNA damage, and therefore induced ATM in a virulence factor-dependent manner. In addition, we found that H. pylori might activate ATM through histone H3 and H4 hyperacetylation and DNA promoter hypomethylation. Our findings show a mechanism associating ATM signaling induction with H. pylori infection.

Role of Streptococcus pneumoniae Proteins in Evasion of Complement-Mediated Immunity.

The complement system plays a central role in immune defense against Streptococcus pneumoniae. In order to evade complement attack, pneumococci have evolved a number of mechanisms that limit complement mediated opsonization and subsequent phagocytosis. This review focuses on the strategies employed by pneumococci to circumvent complement mediated immunity, both in vitro and in vivo. At last, since many of the proteins involved in interactions with complement components are vaccine candidates in different stages of validation, we explore the use of these antigens alone or in combination, as potential vaccine approaches that aim at elimination or drastic reduction in the ability of this bacterium to evade complement.

Helicobacter pylori infection modulates the expression of miRNAs associated with DNA mismatch repair pathway.

Genetic and epigenetic inactivation of DNA mismatch repair (MMR) genes might lead to modifications in cancer-related gene expression and cancer development. Recently, it has been shown that the infection by Helicobacter pylori, the major causative agent of gastric cancer, induces DNA damage and inhibits MMR DNA repair. Also, it has been reported that microRNAs (miRs) have an important role in regulating genomic stability and MMR DNA repair. Thus, the aim of this study was to identify miRs regulating MMR pathway in H. pylori-associated gastric carcinogenesis. To address this question, a gastric epithelial cell line and AGS cancer gastric cells were infected with several H. pylori strains. MMR gene expression and miRs correlating with H. pylori strain infection were evaluated. The results showed that H. pylori infection significantly down-regulated the expression of all selected MMR genes. Also, H. pylori infection modulated the expression of several miRs (including miR-150-5p, miR-155-5p, and miR-3163), after 4, 8, and 12 h of infection. Computational prediction of candidate miRs and their predicted MMR targeting sites were obtained from TargetScan, mirDB, and MetaCore. The generated data indicated that the selected miRs (miR-150-5p, miR-155-5p, and miR-3163) could possibly target and modulate MMR genes (POLD3, MSH2, and MSH3, respectively). The target validation was performed using mimics and luciferase gene reporter assays. Briefly, this study shows that H. pylori impairs MMR DNA repair pathway and identifies miRs that regulate MMR gene expression in gastric cancer. © 2016 Wiley Periodicals, Inc.

Role of streptococcus pneumoniae proteins in evasion of complement-mediated immunity

The complement system plays a central role in immune defense against Streptococcus pneumoniae. In order to evade complement attack, pneumococci have evolved a number of mechanisms that limit complement mediated opsonization and subsequent phagocytosis. This review focuses on the strategies employed by pneumococci to circumvent complement mediated immunity, both in vitro and in vivo. At last, since many of the proteins involved in interactions with complement components are vaccine candidates in different stages of validation, we explore the use of these antigens alone or in combination, as potential vaccine approaches that aim at elimination or drastic reduction in the ability of this bacterium to evade complement.

Yerba mate (Ilex paraguariensis) inhibits lymphocyte activation in vitro.

Yerba mate (YM) has been shown to have anti-inflammatory properties in several studies. However, this effect has been found mainly in obesity-related inflammation. The aim of this work was to study the effect of YM on cultured peripheral blood mononuclear cells to see whether it has anti-inflammatory properties. We stimulated peripheral blood mononuclear cells in vitro with phytohemagglutinin (PHA) in the presence of yerba mate and determined their activation by measuring the expression of CD25 by flow cytometry. We observed that YM treatment produced a dose-dependent reduction in PBMC activation (CD25 positive cells) when they were stimulated with PHA. This effect was also observed in T cells' (CD3 positive) subpopulation. Microarray analysis revealed the differential expression of 128 genes in YM-treated cells. According to a protein-protein interaction database, these genes were highly connected and they are involved in the inflammatory response. In summary, it was demonstrated that YM produces a reduction in the amount of activated cells under the stimulation of PHA. Therefore, it might be used in diseases with an inflammatory component.

Protective effects of chronic treatment with a standardized extract of Ginkgo biloba L. in the prefrontal cortex and dorsal hippocampus of middle-aged rats.

This study assessed the effects of chronic treatment with a standardized extract of Ginkgo biloba L. (EGb) on short-term and long-term memory as well as on anxiety-like and locomotor activity using the plus-maze discriminative avoidance task (PM-DAT). Additionally, we evaluated the antioxidant and neuroprotective effects of EGb on the prefrontal cortex (PFC) and dorsal hippocampus (DH) of middle-aged rats using the comet assay. Twelve-month-old male Wistar rats were administered vehicle or EGb (0.5mgkg(-1) or 1.0gkg(-1)) for 30days. Behavioural data showed that EGb treatment improved short-term memory. Neither an anti-anxiety effect nor a change in locomotor activity was observed. Twenty-four hours after the behavioural tests, the rats were decapitated, and the PFC and DH were quickly dissected out and prepared for the comet assay. The levels of DNA damage in the PFC were significantly lower in rats that were treated with 1.0gkg(-1) EGb. Both doses of EGb decreased H2O2-induced DNA breakage in cortical cells, whereas the levels of DNA damage in the EGb-treated animals were significantly lower than those in the control animals. No significant differences in the level of DNA damage in hippocampal cells were observed among the experimental groups. EGb treatment was not able to reduce H2O2-induced DNA damage in hippocampal cells. Altogether, our data provide the first demonstration that chronic EGb treatment improved the short-term memory of middle-aged rats, an effect that could be associated with a reduction in free radical production in the PFC. These data suggest that EGb treatment might increase the survival of cortical neurons and corroborate and extend the view that EGb has protective and therapeutic properties.

Paradoxical role of SOX2 in gastric cancer.

Sox2 is a critical regulator of embryogenesis and necessary for cellular reprogramming. It also plays an important role in tissue homeostasis and regeneration, maintaining the population of undifferentiated adult stem cells. Like various developmental and stem cell genes, SOX2 is aberrantly expressed and amplified in several human cancers. Moreover, functional studies have shown that it regulates many biological processes including cell proliferation, apoptosis, self-renewal and invasion. While it is oncogenic in most cancers, SOX2 activity is controversial in gastric cancer, where it might behave as a tumor suppressor in some situations. In this review, we discuss its role in cancer biology, with particular attention to what is known about the involvement of SOX2 in gastric cancer biology.

The positive effects of yerba maté (Ilex paraguariensis) in obesity.

The prevalence of obesity has increased worldwide over the past three decades. Global anti-obesity strategies focus on dietary and lifestyle modifications to slow the development of obesity. Research in the nutrition field has recently aroused considerable interest based on the potential of natural products to counteract obesity. Several studies have identified yerba maté (Ilex paraguariensis) as an excellent candidate. In this review, we evaluated the impact of yerba maté on obesity and obesity-related inflammation. Cellular studies demonstrate that yerba maté suppresses adipocyte differentiation and triglyceride accumulation and reduces inflammation. Animal studies show that yerba maté modulates signaling pathways that regulate adipogenesis, antioxidant, anti-inflammatory and insulin signaling responses. In summary, the data presented here showed that the use of yerba maté might be useful against obesity, improving the lipid parameters in humans and animal models. In addition, yerba maté modulates the expression of genes that are changed in the obese state and restores them to more normal levels of expression. In doing so, it addresses several of the abnormal and disease-causing factors associated with obesity. Protective and ameliorative effects on insulin resistance were also observed. Thus, as a general conclusion, it seems that yerba maté beverages and supplements might be helpful in the battle against obesity.

Thalidomide controls adipose tissue inflammation associated with high-fat diet-induced obesity in mice.

INTRODUCTION: Immunosuppressant agents modulate the activity of the immune system and control adipose tissue inflammatory responses associated with obesity. Controlling adipose tissue inflammation represents an interesting option for inhibiting the low-grade inflammatory state in obese subjects and for preventing obesity-associated pathologies. In this work, we assessed the effects of thalidomide on the inflammatory response in adipose tissue as well as on systemic inflammatory marker expression in the well-established high-fat diet-induced obesity mouse model. METHODS: Swiss male mice were fed a high-fat diet (60% kcal from fat) for 12 weeks and received thalidomide for the last 10 days (100 mg.kg-1). Adipokine levels were measured in serum and adipose tissue by EIA and real-time quantitative PCR, respectively. Adipose tissue infiltrating macrophages were identified by immunohistochemistry and western blot analysis of F4/80 marker expression. Other inflammatory markers, such as c-Jun N-terminal kinase (JNK) phosphorylation and monocyte chemoattractant protein-1 (MCP-1) production, were also evaluated by western blot analysis. In vitro assays using 3T3-L1 adipocytes were also conducted to evaluated adipokine release. RESULTS: In obese mice, thalidomide administration induced a reduction in adiposity accompanied by a reduction of tumor necrosis factor-α (TNF-α), leptin and MCP-1 adipose tissue production, macrophage infiltration and JNK activation. TNF-α and leptin serum levels were also reduced by thalidomide treatment in obese mice. In vitro, the release of basal TNF-α and lipopolysaccharide (LPS)-induced MCP-1 was inhibited in 3T3-L1 cells. SIGNIFICANCE: Our results suggest that drugs that can modulate the inflammatory status as well as control adipose tissue expansion could represent an interesting approach in the management of obesity, highlighting the need for further development of such compounds.

Effects of yerba maté, a plant extract formulation ("YGD") and resveratrol in 3T3-L1 adipogenesis.

We aimed to evaluate the in vitro effects of yerba maté, YGD (a herbal preparation containing yerba maté, guarana and damiana), and resveratrol on adipogenesis. The anti-adipogenic effects of yerba mate, YGD, resveratrol and YGD + resveratrol and yerba mate + resveratrol combinations were evaluated in 3T3-L1 cells by Oil Red staining, cellular triglyceride content, and PCR quantitative array. The results demonstrated that all of the tested compounds inhibited adipogenesis. Yerba maté extract significantly down-regulated the expression of genes that play an important role in regulating adipogenesis, such as Adig, Axin, Cebpa, Fgf10, Lep, Lpl, and Pparγ2. In addition, these genes, YGD also repressed Bmp2, Ccnd1, Fasn, and Srebf1. Resveratrol also modulated the expression of Adig, Bmp2, Ccnd1, C/EBPα, Fasn, Fgf10, Lep, Lpl, and Pparγ2. Moreover, resveratrol repressed Cebpb, Cdk4, Fgf2, and Klf15. The yerba maté extract and YGD up-regulated the expression of genes involved in inhibiting adipogenesis, such as Dlk-1, Klf2, and Ucp1. Resveratrol also induced the expression of Klf2 and Ucp1. In addition resveratrol modulated the Ddit3, Foxo1, Sirt1, and Sirt2. The combined effects of these compounds on gene expression showed similar results observed from individual treatments. Our data indicates that the synergy between the compounds favors the inhibition of adipogenesis.