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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.

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.

Currently, tissue product producers try to meet consumers’ requirements to retain their loyalty. In perforated products, such as toilet paper, these requirements involve the paper being portioned along the perforation line and not outside of it. Thus, it becomes necessary to enhance the behavior of the perforation line in perforated tissue papers. The current study aimed to verify if the perforation line for 0° (the solution found in commercial perforated products) is the best solution to maximize the perforation efficiency. A finite element (FE) simulation was used to validate the experimental data, where the deviations from the experiments were 5.2% for the case with a 4 mm perforation length and 8.8% for a perforation of 2 mm, and optimize the perforation efficiency using the genetic algorithm while considering two different cases. In the first case, the blank distance and the perforation line angle were varied, with the best configuration being achieved with a blank distance of 0.1 mm and an inclination angle of 0.56°. For the second case, the blank distance was fixed to 1.0 mm and the only variable to be optimized was the inclination angle of the perforation line. It was found that the best angle inclination was 0.67°. In both cases, it was verified that a slight inclination in the perforation line will favor partitioning and therefore the perforation efficiency.

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.

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.

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.

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.

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.

It has been hypothesized that genetic variation in base excision repair (BER) might modify colorectal adenoma risk. Thus, we evaluated the influence of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in normal and tumor samples from patients with colorectal cancer. The results indicate a downregulation of OGG1 and an upregulation of XRCC1 expression in tumor tissue. Regarding the anatomical location of APE1, OGG1 and PARP-1, a decrease in gene expression was observed among patients with cancer in the rectum. In patients with or without some degree of tumor invasion, a significant downregulation in OGG1 was observed in tumor tissue. Interestingly, when taking into account the tumor stage, patients with more advanced grades (III and IV) showed a significant repression for APE1, OGG1 and PARP-1. XRCC1 expression levels were significantly enhanced in tumor samples and were correlated with all clinical and histopathological data. Concerning the polymorphism T2197G, GG genotype carriers exhibited a significantly reduced expression of genes of the BER repair system (APE1, XRCC1 and PARP1). In summary, our data show that patients with colorectal cancer present expression changes in several BER genes, suggesting a role for APE1, XRCC1, PARP1 and OGG1 and APE1 polymorphism in colorectal carcinogenesis.

BACKGROUND: Among the various diagnostic methods for the detection of Helicobacter pylori infection, histological examination and microbiological processing of gastric biopsy samples are assumed to be the gold standard techniques. AIMS: Since H. pylori culture can be affected by the presence of non-H. pylori bacteria, we evaluated the efficacy of endoscope disinfection and the influence of endoscopic procedures on culture contamination. PATIENTS AND METHODS: The procedures used during the first two routine endoscopies were evaluated during 28 consecutive days. Endoscopy room, forceps and endoscopic channel were analyzed before and after the beginning of normal procedures. After disinfection, a biopsy simulation was performed to verify the gastric bacteria. RESULTS: Endoscope disinfection removed all organisms from forceps and endoscopic channel with 100% efficacy. The most frequent non-H. pylori bacteria detected were Streptococcus bovis, Enterobacter hormaechei, and Staphylococcus aureus. The sensibility of the H. pylori culture was affected by the presence of non-H. pylori bacteria. CONCLUSION:The risk of transmission of microorganisms was not detectable when sterilized biopsy forceps and stringent disinfection standards were employed. Whilst S. bovis and E. hormaechei may be common in gastric microbial flora, the presence of P. aeruginosa and S. aureus indicated that the manipulation of biopsies could be responsible for culture contamination with these bacteria.RACIONAL E OBJETIVOS: Dentre os vários métodos diagnósticos empregados na detecção da infecção por Helicobacter pylori, o diagnóstico histológico e a análise microbiológica de biopsia gástrica são consideradas as técnicas mais sensíveis. Entretanto, a sensibilidade da cultura de H. pylori pode ser reduzida pela presença de outras bactérias. Desse modo, avaliou-se a eficácia da desinfecção do endoscópio e a influência dos procedimentos endoscópicos na contaminação da cultura bacteriana. Para tal, as duas primeiras endoscopias durante 28 dias consecutivos foram estudadas. A sala de endoscopia, o fórceps e o canal do endoscópio foram analisados antes e depois do início dos procedimentos endoscópicos rotineiros. Depois da desinfecção, uma simulação de coleta de biopsia foi realizada para verificar a presença das bactérias gástricas. RESULTADOS: A desinfecção do endoscópio foi capaz de remover todos os organismos do fórceps e do canal do endoscópio. As bactérias não-H. pylori mais freqüentemente detectadas foram Streptococcus bovis, Enterobacter hormaechei e Staphylococcus aureus. Em alguns casos a sensibilidade da cultura do H. pylori foi reduzida pela presença de bactérias contaminantes. CONCLUSÃO: Não houve risco de transmissão de microorganismos quando fórceps esterilizados e desinfecção adequada foram empregadas. A presença de S. bovis e E. hormaechei parece ser comum na microflora gástrica; por outro lado, a detecção de P. aeruginosa e S. aureus indica que a manipulação de biopsias pode ser responsável pela contaminação da cultura por essas bactérias.

Yerba mate (Ilex paraguariensis) is rich in several bioactive compounds that can act as free radical scavengers. Since oxidative DNA damage is involved in various pathological states such as cancer, the aim of this study was to evaluate the antioxidant activity of mate tea as well as the ability to influence DNA repair in male Swiss mice. Forty animals were randomly assigned to four groups. The animals received three different doses of mate tea aqueous extract, 0.5, 1.0 or 2.0 g/kg, for 60 days. After intervention, the liver, kidney and bladder cells were isolated and the DNA damage induced by H2O2 was investigated by the comet assay. The DNA repair process was also investigated for its potential to protect the cells from damage by the same methodology. The data presented here show that mate tea is not genotoxic in liver, kidney and bladder cells. The regular ingestion of mate tea increased the resistance of DNA to H2O2-induced DNA strand breaks and improved the DNA repair after H2O2 challenge in liver cells, irrespective of the dose ingested. These results suggest that mate tea could protect against DNA damage and enhance the DNA repair activity. Protection may be afforded by the antioxidant activity of the mate teas bioactive compounds. [ABSTRACT FROM AUTHOR]

In order to aid the design of bonded joints, a computational tool named System of Analysis for Joints (SAJ) was developed. The software can analyze single and double lap bonded joint with composite-composite or metal-composite materials as adherent parts. Thus, SAJ can calculate the stress distribution, loads and displacements. Their results were compared to finite element software (ABAQUSTM) and to specific composite analysis software (ESACompTM). After that, a study about the influence of joint design parameters on the mechanical behavior of the bonded joint was carried out. In regards to parametric study, SAJ leads to some conclusions, which can be used as a guide during the product design process. Therefore, aided by the computational tool, it is possible to perform a conceptual and preliminary design of bonded joints with more accuracy and varying many parameters (materials; fiber orientation and stacking sequence of the laminate; thickness; overlap length).