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Open AccessArticle
Targeting the MYC Oncogene in Burkitt Lymphoma through HSP90 Inhibition
by , , , , , and
Cancers 2018, 10(11), 448; https://doi.org/10.3390/cancers10110448 (registering DOI) -
Abstract
Overexpression of the MYC oncogene is a key feature of many human malignancies including Burkitt lymphoma. While MYC is widely regarded to be a promising therapeutic target, a clinically effective MYC inhibitor is still elusive. Here, we report an alternative strategy, targeting MYC
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Overexpression of the MYC oncogene is a key feature of many human malignancies including Burkitt lymphoma. While MYC is widely regarded to be a promising therapeutic target, a clinically effective MYC inhibitor is still elusive. Here, we report an alternative strategy, targeting MYC indirectly through inhibition of the HSP90 machinery. We found that inhibition of HSP90 function reduces MYC expression in human Burkitt lymphoma through suppression of MYC transcription and destabilization of MYC protein, thereby diminishing the proliferation of tumor cells. Consistently, treatment of Burkitt lymphoma cell lines with HSP90 inhibitors (17-AAG or 17-DMAG) was accompanied by downregulation of canonical MYC target genes. Combination treatment with 17-DMAG and the proteasome inhibitor, MG-132, led to accumulation of MYC protein, indicating that upon HSP90 inhibition, MYC is degraded by the proteasome. Using co-immunoprecipitation, we furthermore demonstrated a direct interaction between MYC and HSP90, indicating that MYC is an HSP90 client protein in Burkitt lymphoma. Together, we report here the use of HSP90 inhibitors as an alternative approach to target the MYC oncogene and its network in Burkitt lymphoma. Full article
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Open AccessReview
Descriptive Study of the Different Tools Used to Evaluate the Adherence to a Gluten-Free Diet in Celiac Disease Patients
by , , and
Nutrients 2018, 10(11), 1777; https://doi.org/10.3390/nu10111777 (registering DOI) -
Abstract
Celiac disease (CD) is a genetically conditioned autoimmune process that appears in susceptible people. It can affect people of any age, and slightly predominates in females. It has a fairly homogenous global distribution, with an average prevalence of 1–2%, the frequency having increased
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Celiac disease (CD) is a genetically conditioned autoimmune process that appears in susceptible people. It can affect people of any age, and slightly predominates in females. It has a fairly homogenous global distribution, with an average prevalence of 1–2%, the frequency having increased in recent decades. The only effective treatment is a strict and permanent gluten-free diet (GFD), although the level of compliance is poor, at about 50% of cases. To monitor the effectiveness of the GFD, several procedures involving various approaches are employed: (a) Periodic visits by expert Nutritionists; (b) Clinical follow-up; (c) Serological time controls of specific antibodies; (d) Serial endoscopies with collection of duodenal biopsies; (e) Use of structured questionnaires; and (f) Determination of gluten peptides derived from gluten in faeces and/or urine. All of these procedures are useful when applied, alone or in combination, depending on the cases. Some patients will only need to consult to their doctors, while others will require a multidisciplinary approach to assess their compliance with the GFD. In children, normalization of duodenal mucosa was achieved in 95% of cases within two years, while it is more delayed in adults, whose mucosa take longer time (3–5 years) to heal completely. Full article
Open AccessReview
Insight into Influenza: A Virus Cap-Snatching
by , and
Viruses 2018, 10(11), 641; https://doi.org/10.3390/v10110641 (registering DOI) -
Abstract
The influenza A virus (IAV) genome consists of eight single-stranded RNA segments. Each segment is associated with a protein complex, with the 3′ and 5′ ends bound to the RNA-dependent RNA polymerase (RdRp) and the remainder associated with the viral nucleoprotein. During transcription
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The influenza A virus (IAV) genome consists of eight single-stranded RNA segments. Each segment is associated with a protein complex, with the 3′ and 5′ ends bound to the RNA-dependent RNA polymerase (RdRp) and the remainder associated with the viral nucleoprotein. During transcription of viral mRNA, this ribonucleoprotein complex steals short, 5′-capped transcripts produced by the cellular DNA dependent RNA polymerase II (RNAPII) and uses them to prime transcription of viral mRNA. Here, we review the current knowledge on the process of IAV cap-snatching and suggest a requirement for RNAPII promoter-proximal pausing for efficient IAV mRNA transcription. Full article
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Open AccessArticle
Research on Mixed and Classification Simulation Models of Medical Waste—A Case Study in Beijing, China
by and
Sustainability 2018, 10(11), 4226; https://doi.org/10.3390/su10114226 (registering DOI) -
Abstract
Medical waste has strict classification standards. However, in reality, the process of collection and disposal of most medical waste does not strictly follow the corresponding standards, thus resulting in great potential risks to people’s health. Our research analyzed existing problems with medical waste
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Medical waste has strict classification standards. However, in reality, the process of collection and disposal of most medical waste does not strictly follow the corresponding standards, thus resulting in great potential risks to people’s health. Our research analyzed existing problems with medical waste classification management, optimized the medical waste recycling business model, and then used the simulation software AnyLogic to design mixed and classification simulation models based on current literature regarding the standards of medical waste classification and composition in China. Furthermore, we simulated and calculated the generation of nonrecyclable medical waste, recyclable medical waste, and domestic waste in the three models based on 30,000 tons of medical waste generated in Beijing in 2015. We compared and analyzed the output, generation rate, disposal cost, recycling revenue, and cost–benefit based on the disposal cost standards of the Beijing Municipal Commission of Development and Reform and the China Renewable Resources Price Index in Beijing. The importance of strengthening the classification and recycling of medical waste was further validated by modeling and simulation. The study provides an important reference to hospitals, disposal plants, and government regulatory departments in their decision-making. Full article
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Open AccessArticle
Synthesis of Carvone-Derived 1,2,3-Triazoles Study of Their Antioxidant Properties and Interaction with Bovine Serum Albumin
by , , , , , and
Molecules 2018, 23(11), 2991; https://doi.org/10.3390/molecules23112991 (registering DOI) -
Abstract
Natural L-carvone was utilized as a starting material for an efficient synthesis of some terpenyl-derived 1,2,3-triazoles. Chlorination of carvone, followed by nucleophilic substitution with sodium azide resulted in the preparation of 10-azidocarvone. Subsequent CuAAC click reaction with propargylated derivatives provided an efficient synthetic
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Natural L-carvone was utilized as a starting material for an efficient synthesis of some terpenyl-derived 1,2,3-triazoles. Chlorination of carvone, followed by nucleophilic substitution with sodium azide resulted in the preparation of 10-azidocarvone. Subsequent CuAAC click reaction with propargylated derivatives provided an efficient synthetic route to a set of terpenyl-derived conjugates with increased solubility in water. All investigated compounds exhibit high antioxidant activity, which is comparable with that of vitamin C. It was also found that serum albumin and the terpenyl-1,2,3-triazoles hybrids spontaneously undergo reversible binding driven by hydrophobic interactions, suggesting that serum albumin can transport the target triazoles. Full article
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Open AccessArticle
EEG Waveform Analysis of P300 ERP with Applications to Brain Computer Interfaces
by , and
Brain Sci. 2018, 8(11), 199; https://doi.org/10.3390/brainsci8110199 (registering DOI) -
Abstract
The Electroencephalography (EEG) is not just a mere clinical tool anymore. It has become the de-facto mobile, portable, non-invasive brain imaging sensor to harness brain information in real time. It is now being used to translate or decode brain signals, to diagnose diseases
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The Electroencephalography (EEG) is not just a mere clinical tool anymore. It has become the de-facto mobile, portable, non-invasive brain imaging sensor to harness brain information in real time. It is now being used to translate or decode brain signals, to diagnose diseases or to implement Brain Computer Interface (BCI) devices. The automatic decoding is mainly implemented by using quantitative algorithms to detect the cloaked information buried in the signal. However, clinical EEG is based intensively on waveforms and the structure of signal plots. Hence, the purpose of this work is to establish a bridge to fill this gap by reviewing and describing the procedures that have been used to detect patterns in the electroencephalographic waveforms, benchmarking them on a controlled pseudo-real dataset of a P300-Based BCI Speller and verifying their performance on a public dataset of a BCI Competition. Full article
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Open AccessReview
Moral Judgment: An Overlooked Deficient Domain in Multiple Sclerosis?
by and
Behav. Sci. 2018, 8(11), 105; https://doi.org/10.3390/bs8110105 (registering DOI) -
Abstract
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system through which patients can suffer from sensory, motor, cerebellar, emotional, and cognitive symptoms. Although cognitive and behavioral dysfunctions are frequently encountered in MS patients, they have previously received
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Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system through which patients can suffer from sensory, motor, cerebellar, emotional, and cognitive symptoms. Although cognitive and behavioral dysfunctions are frequently encountered in MS patients, they have previously received little attention. Among the most frequently impaired cognitive domains are attention, information processing speed, and working memory, which have been extensively addressed in this population. However, less emphasis has been placed on other domains like moral judgment. The latter is a complex cognitive sphere that implies the individuals’ ability to judge others’ actions and relies on numerous affective and cognitive processes. Moral cognition is crucial for healthy and adequate interpersonal relationships, and its alteration might have drastic impacts on patients’ quality of life. This work aims to analyze the studies that have addressed moral cognition in MS. Only three works have previously addressed moral judgement in this clinical population compared to healthy controls, and none included neuroimaging or physiological measures. Although scarce, the available data suggest a complex pattern of moral judgments that deviate from normal response. This finding was accompanied by socio-emotional and cognitive deficits. Only preliminary data are available on moral cognition in MS, and its neurobiological foundations are still needing to be explored. Future studies would benefit from combining moral cognitive measures with comprehensive neuropsychological batteries and neuroimaging/neurophysiological modalities (e.g., functional magnetic resonance imaging, tractography, evoked potentials, electroencephalography) aiming to decipher the neural underpinning of moral judgement deficits and subsequently conceive potential interventions in MS patients. Full article
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Open AccessArticle
Development of New Analytical Microwave-Assisted Extraction Methods for Bioactive Compounds from Myrtle (Myrtus communis L.)
by , , , , , , , and
Molecules 2018, 23(11), 2992; https://doi.org/10.3390/molecules23112992 (registering DOI) -
Abstract
The phenolic compounds and anthocyanins present in myrtle berries are responsible for its beneficial health properties. In the present study, a new, microwave-assisted extraction for the analysis of both phenolic compounds and anthocyanins from myrtle pulp has been developed. Different extraction variables, including
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The phenolic compounds and anthocyanins present in myrtle berries are responsible for its beneficial health properties. In the present study, a new, microwave-assisted extraction for the analysis of both phenolic compounds and anthocyanins from myrtle pulp has been developed. Different extraction variables, including methanol composition, pH, temperature, and sample–solvent ratio were optimized by applying a Box–Behnken design and response surface methodology. Methanol composition and pH were the most influential variables for the total phenolic compounds (58.20% of the solvent in water at pH 2), and methanol composition and temperature for anthocyanins (50.4% of solvent at 50 °C). The methods developed showed high repeatability and intermediate precision (RSD < 5%). Both methods were applied to myrtle berries collected in two different areas of the province of Cadiz (Spain). Hierarchical clustering analysis results show that the concentration of bioactive compounds in myrtle is related to their geographical origin. Full article
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Open AccessArticle
Study on Damage Accumulation and Life Prediction with Loads below Fatigue Limit Based on a Modified Nonlinear Model
by , , , , and
Materials 2018, 11(11), 2298; https://doi.org/10.3390/ma11112298 (registering DOI) -
Abstract
Most fatigue theories neglect the loads below fatigue limit in damage accumulation, which leads to inconsistency between the predicted and the actual fatigue lives. In this study, a novel damage model is proposed to take into account the loads below fatigue limit from
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Most fatigue theories neglect the loads below fatigue limit in damage accumulation, which leads to inconsistency between the predicted and the actual fatigue lives. In this study, a novel damage model is proposed to take into account the loads below fatigue limit from two aspects: the strengthening effect and the cumulative damage. The strengthening effect is introduced by an exponential function and the cumulative damage is calculated by fuzzy method with membership functions (MFs). The proposed model is verified against the experimental data under variable amplitude loading conditions. It is found the modified model with Cauchy MF significantly reduces the relative error of predicted life from 35.18% (linear model) and 16.09% (original Chaboche model) to 8.38% (proposed model). As a case study, the proposed damage model is implemented to evaluate the service life of a compressor blade under variable amplitude loading spectrum containing small loads below the fatigue limit. Full article
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Open AccessArticle
Associations among High-Quality Protein and Energy Intake, Serum Transthyretin, Serum Amino Acids and Linear Growth of Children in Ethiopia
by , , , , , , , and
Nutrients 2018, 10(11), 1776; https://doi.org/10.3390/nu10111776 (registering DOI) -
Abstract
Limited evidence is available on the associations of high-quality protein and energy intake, serum transthyretin (TTR), serum amino acids and serum insulin-like growth factor-1 (IGF-1) with linear growth of young children. Data collected during the baseline of a randomized control trial involving rural
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Limited evidence is available on the associations of high-quality protein and energy intake, serum transthyretin (TTR), serum amino acids and serum insulin-like growth factor-1 (IGF-1) with linear growth of young children. Data collected during the baseline of a randomized control trial involving rural Ethiopian children aged 6–35 months (n = 873) were analyzed to evaluate the associations among height/length-for-age z-scores, dietary intakes, and these biomarkers (i.e., serum level of TTR, IGF-1, tryptophan and lysine, and inflammation). The prevalence of stunting was higher for children >23 months (38%) than ≤23 months (25%). The prevalence of inflammation was 35% and of intestinal parasites 48%. Three-quarters of the children were energy deficient, and stunted children had lower daily energy intake that non-stunted children (p < 0.05). Intakes of tryptophan, protein, and energy, and serum levels of tryptophan and IGF-1 were positively correlated with the linear growth of children. Controlling for inflammation, intestinal parasites, and sociodemographic characteristics, daily tryptophan (b = 0.01, p = 0.001), protein (b = 0.01, p = 0.01) and energy (b = 0.0003, p = 0.04) intakes and serum TTR (b = 2.58, p = 0.04) and IGF-1 (b = 0.01, p = 0.003) were positively associated with linear growth of children. Linear growth failure in Ethiopian children is likely associated with low quality protein intake and inadequate energy intake. Nutrition programs that emphasize improved protein quantity and quality and energy intake may enhance the linear growth of young children and need to be further investigated in longitudinal and interventional studies. Full article
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