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Biomolecules, Volume 8, Issue 3 (September 2018)

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Open AccessArticle Intrinsic Iron Release Is Associated with Lower Mortality in Patients with Stable Coronary Artery Disease—First Report on the Prospective Relevance of Intrinsic Iron Release
Biomolecules 2018, 8(3), 72; https://doi.org/10.3390/biom8030072
Received: 9 July 2018 / Revised: 3 August 2018 / Accepted: 3 August 2018 / Published: 9 August 2018
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Abstract
Intrinsic iron release is discussed to have favorable effects in coronary artery disease (CAD). The aim of this study was to evaluate the prognostic relevance of intrinsic iron release in patients with CAD. Intrinsic iron release was based on a definition including hepcidin
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Intrinsic iron release is discussed to have favorable effects in coronary artery disease (CAD). The aim of this study was to evaluate the prognostic relevance of intrinsic iron release in patients with CAD. Intrinsic iron release was based on a definition including hepcidin and soluble transferrin receptor (sTfR). In a cohort of 811 patients with angiographically documented CAD levels of hepcidin and sTfR were measured at baseline. Systemic body iron release was defined as low levels of hepcidin (<24 ng/mL) and high levels of sTfR (≥2 mg/L). A commercially available ELISA (DRG) was used for measurements of serum hepcidin. Serum sTfR was determined by using an automated immunoassay (). Cardiovascular mortality was the main outcome measure. The criteria of intrinsic iron release were fulfilled in 32.6% of all patients. Significantly lower cardiovascular mortality rates were observed in CAD patients with systemic iron release. After adjustment for body mass index, smoking status, hypertension, diabetes, dyslipidemia, sex, and age, the hazard ratio for future cardiovascular death was 0.41. After an additional adjustment for surrogates of the size of myocardial necrosis (troponin I), anemia (hemoglobin), and cardiac function and heart failure severity (N-terminal pro B-type natriuretic peptide), this association did not change (Hazard ratio 0.37 (95% confidence interval 0.14–0.99), p = 0.047). In conclusion, significantly lower cardiovascular mortality rates were observed in CAD patients with intrinsic iron release shown during follow-up. Full article
(This article belongs to the Special Issue Biomolecules for Translational Approaches in Cardiology)
Open AccessArticle On Eccentricity-Based Topological Indices Study of a Class of Porphyrin-Cored Dendrimers
Biomolecules 2018, 8(3), 71; https://doi.org/10.3390/biom8030071
Received: 11 June 2018 / Revised: 29 July 2018 / Accepted: 1 August 2018 / Published: 7 August 2018
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Abstract
It is revealed from the previous studies that there is a strong relation between the chemical characteristic of a chemical compound and its molecular structure. Topological indices defined on the molecular structure of biomolecules can help to gain a better understanding of their
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It is revealed from the previous studies that there is a strong relation between the chemical characteristic of a chemical compound and its molecular structure. Topological indices defined on the molecular structure of biomolecules can help to gain a better understanding of their physical features and biological activities. Eccentricity connectivity indices are distance-based molecular structure descriptors that have been used for the mathematical modeling of biological activities of diverse nature. As the porphyrin has photofunctional properties, such as a large absorption cross-section, fluorescence emission, and photosensitizing properties, due to these properties, porphyrin dendrimers can be used as photofunctional nanodevices. In this paper, we compute the exact formulae of different versions of eccentric connectivity index and their corresponding polynomials for a class of porphyrin-cored dendrimers. The results obtained can be used in computer-aided molecular design methods applied to pharmaceutical engineering. Full article
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Open AccessArticle Functional Annotation of Caenorhabditis elegans Genes by Analysis of Gene Co-Expression Networks
Biomolecules 2018, 8(3), 70; https://doi.org/10.3390/biom8030070
Received: 3 July 2018 / Revised: 30 July 2018 / Accepted: 1 August 2018 / Published: 3 August 2018
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Abstract
Caenorhabditis elegans (C. elegans) is a well-characterized metazoan, whose transcriptome has been profiled in different tissues, development stages, or other conditions. Large-scale transcriptomes can be reused for gene function annotation through systematic analysis of gene co-expression relationships. We collected 2101 microarray
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Caenorhabditis elegans (C. elegans) is a well-characterized metazoan, whose transcriptome has been profiled in different tissues, development stages, or other conditions. Large-scale transcriptomes can be reused for gene function annotation through systematic analysis of gene co-expression relationships. We collected 2101 microarray data from National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO), and identified 48 modules of co-expressed genes that correspond to tissues, development stages, and other experimental conditions. These modules provide an overview of the transcriptional organizations that may work under different conditions. By analyzing higher-order module networks, we found that nucleus and plasma membrane modules are more connected than other intracellular modules. Module-based gene function annotation may help to extend the candidate cuticle gene list. A comparison with other published data validates the credibility of our result. Our findings provide a new source for future gene discovery in C. elegans. Full article
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Open AccessReview The Role of Calcium in Inflammation-Associated Bone Resorption
Biomolecules 2018, 8(3), 69; https://doi.org/10.3390/biom8030069
Received: 28 June 2018 / Revised: 25 July 2018 / Accepted: 27 July 2018 / Published: 1 August 2018
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Abstract
The aim of this mini-review is to discuss the role of calcium in the process of cytokine-mediated bone resorption in an effort to understand the role circulating calcium may play in the resorption of bone. The liberation of calcium and possibly phosphorus and
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The aim of this mini-review is to discuss the role of calcium in the process of cytokine-mediated bone resorption in an effort to understand the role circulating calcium may play in the resorption of bone. The liberation of calcium and possibly phosphorus and magnesium by bone resorption may sustain and intensify the inflammatory response. We used a burn injury setting in humans and a burn injury model in animals in order to examine the effects on the bone of the systemic inflammatory response and identified the parathyroid calcium-sensing receptor as the mediator of increasing bone resorption, hence higher interleukin (IL)-1 production, and decreasing bone resorption, hence the lowering of circulating ionized calcium concentration. Thus, extracellular calcium, by means of the parathyroid calcium-sensing receptor, is able to modulate inflammation-mediated resorption. Full article
(This article belongs to the Special Issue Key Biomolecules in Bone Resorption)
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Open AccessArticle Cytotoxicity of Different Concentrations of Three Root Canal Sealers on Human Mesenchymal Stem Cells
Biomolecules 2018, 8(3), 68; https://doi.org/10.3390/biom8030068
Received: 12 July 2018 / Revised: 27 July 2018 / Accepted: 30 July 2018 / Published: 1 August 2018
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Abstract
This study assessed the dose-dependent effect on the cytotoxicity of BioRoot RCS (BR) and Endosequence BC (BC) sealers in human bone marrow mesenchymal stem cells (hMSCs) compared to those of the AH Plus sealer. Cells were exposed to different dilutions of extracts from
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This study assessed the dose-dependent effect on the cytotoxicity of BioRoot RCS (BR) and Endosequence BC (BC) sealers in human bone marrow mesenchymal stem cells (hMSCs) compared to those of the AH Plus sealer. Cells were exposed to different dilutions of extracts from freshly prepared sealers (1:2, 1:8, 1:32). Unexposed cells acted as the negative control. Cytotoxicity was evaluated by an alamar blue assay. Cell morphology was analyzed by using scanning electron microscopy after exposure to the different sealers’ extracts. Statistical analysis was performed using a one-way analysis of variance and the Bonferroni post hoc test (p < 0.05). The cytotoxicities of BC and BR were less than that of AH Plus. In the presence of 1:2 BR, the cell proliferation was significantly lower than the control. At 1:8 and 1:32 concentrations, both the tricalcium silicate sealers led to similar cellular proliferation. Cells in BC and BR sealers’ extracts spread better than those in AH Plus extract. Full article
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Open AccessArticle Model Senescent Microglia Induce Disease Related Changes in α-Synuclein Expression and Activity
Biomolecules 2018, 8(3), 67; https://doi.org/10.3390/biom8030067
Received: 4 July 2018 / Revised: 24 July 2018 / Accepted: 26 July 2018 / Published: 1 August 2018
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Abstract
Aging is the most prominent risk factor for most neurodegenerative diseases. However, incorporating aging-related changes into models of neurodegeneration rarely occurs. One of the significant changes that occurs in the brain as we age is the shift in phenotype of the resident microglia
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Aging is the most prominent risk factor for most neurodegenerative diseases. However, incorporating aging-related changes into models of neurodegeneration rarely occurs. One of the significant changes that occurs in the brain as we age is the shift in phenotype of the resident microglia population to one less able to respond to deleterious changes in the brain. These microglia are termed dystrophic microglia. In order to better model neurodegenerative diseases, we have developed a method to convert microglia into a senescent phenotype in vitro. Mouse microglia grown in high iron concentrations showed many characteristics of dystrophic microglia including, increased iron storage, increased expression of proteins, such as ferritin and the potassium channel, Kv1.3, increased reactive oxygen species production and cytokine release. We have applied this new model to the study of α-synuclein, a protein that is closely associated with a number of neurodegenerative diseases. We have shown that conditioned medium from our model dystrophic microglia increases α-synuclein transcription and expression via tumor necrosis factor alpha (TNFα) and mediated through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The conditioned medium also decreases the formation of α-synuclein tetramers, associated ferrireductase activity, and increases aggregates of α-synuclein. The results suggest that we have developed an interesting new model of aged microglia and that factors, including TNFα released from dystrophic microglia could have a significant influence on the pathogenesis of α-synuclein related diseases. Full article
(This article belongs to the Special Issue Alpha-Synuclein: From function to Disfunction)
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Open AccessReview Potential Impact of Oral Inflammations on Cardiac Functions and Atrial Fibrillation
Biomolecules 2018, 8(3), 66; https://doi.org/10.3390/biom8030066
Received: 21 June 2018 / Revised: 14 July 2018 / Accepted: 26 July 2018 / Published: 1 August 2018
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Abstract
Inflammation may be a risk factor for atrial fibrillation (AF). Oral infections frequently lead to chronic inflammation, such as gingivitis, periodontitis, and endodontic lesions. In this narrative review, we consider five basic pathogenic mechanisms that involve oral infections and inflammations in the pathogenesis
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Inflammation may be a risk factor for atrial fibrillation (AF). Oral infections frequently lead to chronic inflammation, such as gingivitis, periodontitis, and endodontic lesions. In this narrative review, we consider five basic pathogenic mechanisms that involve oral infections and inflammations in the pathogenesis of AF: (1) low level bacteremia by which oral bacteria enter the blood stream at inflamed sites of the oral cavity and invade the heart; (2) Systemic inflammation induced by inflammatory mediators, which are released from the sites of oral inflammation into the blood stream, affecting cardiac remodeling; (3) autoimmunity against molecular structures expressed in the heart caused by the host immune response to specific components of oral pathogens; (4) potentially arrhythmic effects mediated by activation of the autonomous nervous system triggered by oral inflammations; and (5) arrhythmic effects resulting from specific bacterial toxins that are produced by oral pathogenic bacteria. A number of studies support the involvement of all five mechanisms, suggesting a potentially complex contribution of oral inflammations to the pathogenesis of AF. Full article
(This article belongs to the Special Issue Biomolecules for Translational Approaches in Cardiology)
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Open AccessReview Role of Uric Acid in Semen
Biomolecules 2018, 8(3), 65; https://doi.org/10.3390/biom8030065
Received: 28 June 2018 / Revised: 15 July 2018 / Accepted: 26 July 2018 / Published: 31 July 2018
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Abstract
Since 1963, various research studies and reports have demonstrated the role of uric acid (2,6,8-trihydroxypurine), an end product of adenosine and guanosine catabolism, on semen quality and sperm function. However, this effect has not yet been collectively discussed, even though uric acid has
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Since 1963, various research studies and reports have demonstrated the role of uric acid (2,6,8-trihydroxypurine), an end product of adenosine and guanosine catabolism, on semen quality and sperm function. However, this effect has not yet been collectively discussed, even though uric acid has been a well-recognized constituent in semen. Here, we systematically and comprehensively discuss and summarize the role/effect of uric acid in semen quality by searching the main databases for English language articles considering this topic. Additionally, certain significant and relevant papers were considered to support discussions and perceptions. In conclusion, uric acid contributes to maintaining and enhancing sperm motility, viability, and morphology; therefore, protecting sperm function and fertilizing ability. This contribution is performed mainly by neutralizing the damaging effect of oxidizing (e.g., endogenous free radicals and exogenous toxins) and nitrating agents and enhancing certain bioactive enzymes in spermatozoa. In contrast, high levels of uric acid may induce adverse effects to sperm function, at least in part, by reducing the activity of vital enzymes in spermatozoa. However, further research, mainly clinical, is still required to fully explore the role/effect of uric acid in semen. Full article
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Open AccessArticle Understanding the Positional Binding and Substrate Interaction of a Highly Thermostable GH10 Xylanase from Thermotoga maritima by Molecular Docking
Biomolecules 2018, 8(3), 64; https://doi.org/10.3390/biom8030064
Received: 18 June 2018 / Revised: 24 July 2018 / Accepted: 26 July 2018 / Published: 30 July 2018
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Abstract
Glycoside hydrolase family 10 (GH10) xylanases are responsible for enzymatic cleavage of the internal glycosidic linkages of the xylan backbone, to generate xylooligosaccharides (XOS) and xyloses. The topologies of active-site cleft determine the substrate preferences and product profiles of xylanases. In this study,
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Glycoside hydrolase family 10 (GH10) xylanases are responsible for enzymatic cleavage of the internal glycosidic linkages of the xylan backbone, to generate xylooligosaccharides (XOS) and xyloses. The topologies of active-site cleft determine the substrate preferences and product profiles of xylanases. In this study, positional bindings and substrate interactions of TmxB, one of the most thermostable xylanases characterized from Thermotoga maritima to date, was investigated by docking simulations. XOS with backbone lengths of two to five (X2–X5) were docked into the active-site cleft of TmxB by AutoDock The modeled complex structures provided a series of snapshots of the interactions between XOS and TmxB. Changes in binding energy with the length of the XOS backbone indicated the existence of four effective subsites in TmxB. The interaction patterns at subsites −2 to +1 in TmxB were conserved among GH10 xylanases whereas those at distal aglycone subsite +2, consisting of the hydrogen bond network, was unique for TmxB. This work helps in obtaining an in-depth understanding of the substrate-binding property of TmxB and provides a basis for rational design of mutants with desired product profiles. Full article
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Open AccessArticle Low-Circulating Homoarginine is Associated with Dilatation and Decreased Function of the Left Ventricle in the General Population
Biomolecules 2018, 8(3), 63; https://doi.org/10.3390/biom8030063
Received: 1 June 2018 / Revised: 10 July 2018 / Accepted: 19 July 2018 / Published: 30 July 2018
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Abstract
Low homoarginine is an independent marker of mortality in heart failure patients and incident cardiovascular events. Whether homoarginine is related with healthier cardiac structure and function is currently unclear. We used data of the population-based “Study of Health in Pomerania” (SHIP-Trend) to assess
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Low homoarginine is an independent marker of mortality in heart failure patients and incident cardiovascular events. Whether homoarginine is related with healthier cardiac structure and function is currently unclear. We used data of the population-based “Study of Health in Pomerania” (SHIP-Trend) to assess this relation. Homoarginine was measured in serum using liquid chromatography-tandem mass spectrometry. Linear regression models assessed the relation between homoarginine and several structural as well as functional parameters and N-terminal pro B-type natriuretic peptide (NTproBNP). All models were adjusted for age, sex, body mass index, and renal function. A total of 3113 subjects (median age 48 (25th percentile 37 to 75th percentile 60) years, 46% male) were included. A standard deviation decrease in homoarginine was associated with a larger left ventricular diastolic diameter (0.3; 95%-confidence interval (CI): 0.2 to 0.5 mm; p < 0.001), left ventricular systolic diameter (0.38; 95%-CI: −0.22 to 0.54 mm; p < 0.001) as well as a less relative wall thickness (–0.003 95%-CI: −0.006 to −0.0008; p = 0.01), left ventricular ejection fraction (–0.47; 95%-CI: –0.79 to −0.15%; p < 0.01) and fractional shortening (−0.35; 95%-CI: −0.62 to 0.07%; p = 0.01). Low homoarginine was also related to higher NTproBNP (−0.02 95%-CI: −0.034 to −0.009 log pg/mL; p < 0.01). Lower serum homoarginine is associated with dilatation of the heart and decreased function. Prospective clinical studies should assess if homoarginine supplementation improves cardiac health in subjects with low serum concentrations. Full article
(This article belongs to the Special Issue Biomolecules for Translational Approaches in Cardiology)
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Open AccessArticle The Use of a Molybdenum Polyoxometalated Compound to Increase the Amount of Extractives from Wood Wastes
Biomolecules 2018, 8(3), 62; https://doi.org/10.3390/biom8030062
Received: 20 June 2018 / Revised: 25 July 2018 / Accepted: 25 July 2018 / Published: 28 July 2018
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Abstract
The treatment of wood wastes of Castanea sativa L., Quercus frainetto, Larix decidua, and Paulownia tomentosa S. in autoclave in the presence of micrometric crystals of H3PMo12O40 showed an impressive increase of the amount of extractives.
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The treatment of wood wastes of Castanea sativa L., Quercus frainetto, Larix decidua, and Paulownia tomentosa S. in autoclave in the presence of micrometric crystals of H3PMo12O40 showed an impressive increase of the amount of extractives. The extractives were mainly constituted of insoluble compounds that were analyzed by using gas chromatography-mass spectrometry (GC-MS) after acetylation. The GC-MS analysis of the chloroform soluble fraction of the extractives obtained from sativa showed the presence of methyl hexadecanoate and octadecanoic acid, that of the extractives of frainetto showed the presence of octadecanal and some long chain hydrocarbons. decidua extracts showed the presence of large amounts of sesamin, while the extractives of P tomentosa revealed the presence of 4-hydroxy-3,5-dimethoxybenzaldehyde, 4-hydroxy-3,5-dimethoxycimmanaldehyde, and relevant amounts of long chain hydrocarbons. The insoluble fraction showed the presence of relevant amounts of several carbohydrates and, in the case of C. sativa, of inositol. Full article
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Open AccessFeature PaperArticle Flavonoids as Putative Epi-Modulators: Insight into Their Binding Mode with BRD4 Bromodomains Using Molecular Docking and Dynamics
Biomolecules 2018, 8(3), 61; https://doi.org/10.3390/biom8030061
Received: 22 June 2018 / Revised: 14 July 2018 / Accepted: 18 July 2018 / Published: 23 July 2018
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Abstract
Flavonoids are widely recognized as natural polydrugs, given their anti-inflammatory, antioxidant, sedative, and antineoplastic activities. Recently, different studies showed that flavonoids have the potential to inhibit bromodomain and extraterminal (BET) bromodomains. Previous reports suggested that flavonoids bind between the Z and A loops
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Flavonoids are widely recognized as natural polydrugs, given their anti-inflammatory, antioxidant, sedative, and antineoplastic activities. Recently, different studies showed that flavonoids have the potential to inhibit bromodomain and extraterminal (BET) bromodomains. Previous reports suggested that flavonoids bind between the Z and A loops of the bromodomain (ZA channel) due to their orientation and interactions with P86, V87, L92, L94, and N140. Herein, a comprehensive characterization of the binding modes of fisetin and the biflavonoid, amentoflavone, is discussed. To this end, both compounds were docked with BET bromodomain 4 (BRD4) using four docking programs. The results were post-processed with protein–ligand interaction fingerprints. To gain further insight into the binding mode of the two natural products, the docking results were further analyzed with molecular dynamics simulations. The results showed that amentoflavone makes numerous contacts in the ZA channel, as previously described for flavonoids and kinase inhibitors. It was also found that amentoflavone can potentially make contacts with non-canonical residues for BET inhibition. Most of these contacts were not observed with fisetin. Based on these results, amentoflavone was experimentally tested for BRD4 inhibition, showing activity in the micromolar range. This work may serve as the basis for scaffold optimization and the further characterization of flavonoids as BET inhibitors. Full article
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Open AccessArticle Adverse Outcome Prediction of Iron Deficiency in Patients with Acute Coronary Syndrome
Biomolecules 2018, 8(3), 60; https://doi.org/10.3390/biom8030060
Received: 8 June 2018 / Revised: 9 July 2018 / Accepted: 16 July 2018 / Published: 20 July 2018
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Abstract
Acute myocardial infarction remains a leading cause of morbidity and mortality. While iron deficient heart failure patients are at increased risk of future cardiovascular events and see improvement with intravenous supplementation, the clinical relevance of iron deficiency in acute coronary syndrome remains unclear.
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Acute myocardial infarction remains a leading cause of morbidity and mortality. While iron deficient heart failure patients are at increased risk of future cardiovascular events and see improvement with intravenous supplementation, the clinical relevance of iron deficiency in acute coronary syndrome remains unclear. We aimed to evaluate the prognostic value of iron deficiency in the acute coronary syndrome (ACS). Levels of ferritin, iron, and transferrin were measured at baseline in 836 patients with ACS. A total of 29.1% was categorized as iron deficient. The prevalence of iron deficiency was clearly higher in women (42.8%), and in patients with anemia (42.5%). During a median follow-up of 4.0 years, 111 subjects (13.3%) experienced non-fatal myocardial infarction (MI) and cardiovascular mortality as combined endpoint. Iron deficiency strongly predicted non-fatal MI and cardiovascular mortality with a hazard ratio (HR) of 1.52 (95% confidence interval (CI) 1.03-2.26; p = 0.037) adjusted for age, sex, hypertension, smoking status, diabetes, hyperlipidemia, body-mass-index (BMI) This association remained significant (HR 1.73 (95% CI 1.07–2.81; p = 0.026)) after an additional adjustment for surrogates of cardiac function and heart failure severity (N-terminal pro B-type natriuretic peptide, NT-proBNP), for the size of myocardial necrosis (troponin), and for anemia (hemoglobin). Survival analyses for cardiovascular mortality and MI provided further evidence for the prognostic relevance of iron deficiency (HR 1.50 (95% CI 1.02–2.20)). Our data showed that iron deficiency is strongly associated with adverse outcome in acute coronary syndrome. Full article
(This article belongs to the Special Issue Biomolecules for Translational Approaches in Cardiology)
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Open AccessArticle The Role of Specific Chemokines in the Amelioration of Colitis by Appendicitis and Appendectomy
Biomolecules 2018, 8(3), 59; https://doi.org/10.3390/biom8030059
Received: 13 June 2018 / Revised: 3 July 2018 / Accepted: 16 July 2018 / Published: 20 July 2018
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Abstract
The appendix contains abundant lymphoid tissue and is constantly exposed to gut flora. When completed at a young age, appendicitis followed by appendectomy (AA) prevents or significantly ameliorates Inflammatory Bowel Diseases (IBDs) in later life. Inflammatory bowel disease comprises Crohn’s disease and ulcerative
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The appendix contains abundant lymphoid tissue and is constantly exposed to gut flora. When completed at a young age, appendicitis followed by appendectomy (AA) prevents or significantly ameliorates Inflammatory Bowel Diseases (IBDs) in later life. Inflammatory bowel disease comprises Crohn’s disease and ulcerative colitis. Our murine AA model is the only existing experimental model of AA. In our unique model, AA performed in the most proximal colon limits colitis pathology in the most distal colon by curbing T-helper 17 cell activity, diminishing autophagy, modulating interferon activity-associated molecules, and suppressing endothelin vaso-activity-mediated immunopathology. In the research presented in this paper, we have examined the role of chemokines in colitis pathology with our murine AA model. Chemokines are a family of small cytokines with four conserved cysteine residues. Chemokines induce chemotaxis in adjacent cells with corresponding receptors. All 40 known chemokine genes and 24 chemokine receptor genes were examined for gene expression levels in distal colons three days post-AA and 28 days post-AA. At 28 days post-AA, the chemokine gene CCL5 was significantly upregulated. Furthermore, Gene Set Enrichment Analysis (GSEA) showed upregulation of seven CCL5-associated gene-sets 28 days post-AA in contrast to just one gene-set downregulated at the same time-point. The chemokine gene CXCL11 was significantly upregulated three days post-AA and 28 days post-AA. Evaluation using GSEA showed upregulation of six CXCL11-associated gene sets but no downregulation of any gene set. At 28 days post-AA, CCL17 gene expression was significantly downregulated. There was no expression of any chemokine receptor gene three days post-AA, but CCR10 was the only chemokine receptor gene that displayed differential gene expression (upregulation) 28 days post-AA. No CCR10-associated gene set was upregulated in GSEA in contrast to one downregulated gene set. Our analysis resulted in identifying three new therapeutic targets towards ameliorating colitis: CCL5, CXCL11, and CCL17. While CCL5 and CXCL11 are good therapeutic chemokine candidates to be exogenously administered, CCL17 is a good candidate chemokine to competitively inhibit or limit colitis pathology. Full article
(This article belongs to the Special Issue The Role of Chemokines in Inflammatory Pathologies)
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Open AccessFeature PaperReview Novel Approaches for BAV Aortopathy Prediction—Is There a Need for Cohort Studies and Biomarkers?
Biomolecules 2018, 8(3), 58; https://doi.org/10.3390/biom8030058
Received: 30 May 2018 / Revised: 9 July 2018 / Accepted: 13 July 2018 / Published: 19 July 2018
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Abstract
Bicuspid aortic valve (BAV) disease is the most common congenital malformation of the human heart with a prevalence of 1–2% in the general population. More than half of patients with a BAV present with a dilated proximal aorta (so-called bicuspid aortopathy) which is
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Bicuspid aortic valve (BAV) disease is the most common congenital malformation of the human heart with a prevalence of 1–2% in the general population. More than half of patients with a BAV present with a dilated proximal aorta (so-called bicuspid aortopathy) which is associated with an enhanced risk of life-threatening aortic complications. Up to now, the pathogenesis of bicuspid aortopathy as well as the risk stratification of aortic complications has not yet been sufficiently clarified. Recent findings have shown that bicuspid aortopathy features phenotypic heterogeneity. Two distinct valvulo-aortic phenotypes, the so-called root phenotype, as well as a dilation of the tubular ascending aorta, coincide with a significantly different risk for aortal complications. However, the phenotype-based classification that is only based on these two clinical forms is not sufficient to estimate the risk of aortal complications in a prognostically relevant way. Therefore, there is growing clinical interest to assess novel approaches in BAV research and to introduce circulating biomarkers as an elegant diagnostic tool to improve risk stratification in BAV aortopathy. A large scale epidemiological cohort study, ranking from apparently healthy individuals to disease patients, and comprehensive biobanks provide the opportunity to study BAV disease and its complications and to identify novel biomarkers for BAV aortopathy surveillance and prognosis. Firstly, the data indicate that several protein-based biomarkers and non-coding RNA molecules, in particular circulating microRNAs, can serve as relevant molecular biomarkers to predict the course of BAV-associated aortopathy. Here, we review the current literature and knowledge about BAV from a clinical point of view, and report about novel approaches in BAV biomarker research. Full article
(This article belongs to the Special Issue Biomolecules for Translational Approaches in Cardiology)
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Open AccessReview Calmodulin: A Multitasking Protein in Kv7.2 Potassium Channel Functions
Biomolecules 2018, 8(3), 57; https://doi.org/10.3390/biom8030057
Received: 26 June 2018 / Revised: 13 July 2018 / Accepted: 14 July 2018 / Published: 18 July 2018
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Abstract
The ubiquitous calcium transducer calmodulin (CaM) plays a pivotal role in many cellular processes, regulating a myriad of structurally different target proteins. Indeed, it is unquestionable that CaM is the most relevant transductor of calcium signals in eukaryotic cells. During the last two
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The ubiquitous calcium transducer calmodulin (CaM) plays a pivotal role in many cellular processes, regulating a myriad of structurally different target proteins. Indeed, it is unquestionable that CaM is the most relevant transductor of calcium signals in eukaryotic cells. During the last two decades, different studies have demonstrated that CaM mediates the modulation of several ion channels. Among others, it has been indicated that Kv7.2 channels, one of the members of the voltage gated potassium channel family that plays a critical role in brain excitability, requires CaM binding to regulate the different mechanisms that govern its functions. The purpose of this review is to provide an overview of the most recent advances in structure–function studies on the role of CaM regulation of Kv7.2 and the other members of the Kv7 family. Full article
(This article belongs to the Special Issue Calcium Binding Proteins: Structure, Properties, Functions)
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Open AccessFeature PaperArticle In Silico HCT116 Human Colon Cancer Cell-Based Models En Route to the Discovery of Lead-Like Anticancer Drugs
Biomolecules 2018, 8(3), 56; https://doi.org/10.3390/biom8030056
Received: 11 June 2018 / Revised: 10 July 2018 / Accepted: 11 July 2018 / Published: 17 July 2018
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Abstract
To discover new inhibitors against the human colon carcinoma HCT116 cell line, two quantitative structure–activity relationship (QSAR) studies using molecular and nuclear magnetic resonance (NMR) descriptors were developed through exploration of machine learning techniques and using the value of half maximal inhibitory concentration
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To discover new inhibitors against the human colon carcinoma HCT116 cell line, two quantitative structure–activity relationship (QSAR) studies using molecular and nuclear magnetic resonance (NMR) descriptors were developed through exploration of machine learning techniques and using the value of half maximal inhibitory concentration (IC50). In the first approach, A, regression models were developed using a total of 7339 molecules that were extracted from the ChEMBL and ZINC databases and recent literature. The performance of the regression models was successfully evaluated by internal and external validations, the best model achieved R2 of 0.75 and 0.73 and root mean square error (RMSE) of 0.66 and 0.69 for the training and test sets, respectively. With the inherent time-consuming efforts of working with natural products (NPs), we conceived a new NP drug hit discovery strategy that consists in frontloading samples with 1D NMR descriptors to predict compounds with anticancer activity prior to bioactivity screening for NPs discovery, approach B. The NMR QSAR classification models were built using 1D NMR data (1H and 13C) as descriptors, from 50 crude extracts, 55 fractions and five pure compounds obtained from actinobacteria isolated from marine sediments collected off the Madeira Archipelago. The overall predictability accuracies of the best model exceeded 63% for both training and test sets. Full article
(This article belongs to the Special Issue Machine Learning for Molecular Modelling in Drug Design)
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Open AccessArticle Developments in Cell-Penetrating Peptides as Antiviral Agents and as Vehicles for Delivery of Peptide Nucleic Acid Targeting Hepadnaviral Replication Pathway
Biomolecules 2018, 8(3), 55; https://doi.org/10.3390/biom8030055
Received: 14 June 2018 / Revised: 10 July 2018 / Accepted: 11 July 2018 / Published: 16 July 2018
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Abstract
Alternative therapeutic approaches against chronic hepatitis B virus (HBV) infection need to be urgently developed because current therapies are only virostatic. In this context, cell penetration peptides (CPPs) and their Peptide Nucleic Acids (PNAs) cargoes appear as a promising novel class of biologically
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Alternative therapeutic approaches against chronic hepatitis B virus (HBV) infection need to be urgently developed because current therapies are only virostatic. In this context, cell penetration peptides (CPPs) and their Peptide Nucleic Acids (PNAs) cargoes appear as a promising novel class of biologically active compounds. In this review we summarize different in vitro and in vivo studies, exploring the potential of CPPs as vehicles for intracellular delivery of PNAs targeting hepadnaviral replication. Thus, studies conducted in the duck HBV (DHBV) infection model showed that conjugation of (D-Arg)8 CPP to PNA targeting viral epsilon (ε) were able to efficiently inhibit viral replication in vivo following intravenous administration to ducklings. Unexpectedly, some CPPs, (D-Arg)8 and Decanoyl-(D-Arg)8, alone displayed potent antiviral effect, altering late stages of DHBV and HBV morphogenesis. Such antiviral effects of CPPs may affect the sequence-specificity of CPP-PNA conjugates. By contrast, PNA conjugated to (D-Lys)4 inhibited hepadnaviral replication without compromising sequence specificity. Interestingly, Lactose-modified CPP mediated the delivery of anti-HBV PNA to human hepatoma cells HepaRG, thus improving its antiviral activity. In light of these promising data, we believe that future studies will open new perspectives for translation of CPPs and CPP-PNA based technology to therapy of chronic hepatitis B. Full article
(This article belongs to the Special Issue Cell Penetrating Peptides)
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Open AccessCommunication A Novel Class of tRNA-Derived Small Non-Coding RNAs Respond to Myocardial Hypertrophy and Contribute to Intergenerational Inheritance
Biomolecules 2018, 8(3), 54; https://doi.org/10.3390/biom8030054
Received: 14 April 2018 / Revised: 12 June 2018 / Accepted: 9 July 2018 / Published: 16 July 2018
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Abstract
tRNA-derived fragments (tRFs) are a new class of non-coding RNA that play an important role in regulating cellular RNA processing and protein translation. However, there is currently no study reporting the influence of tRFs on myocardial hypertrophy. In this study, we used an
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tRNA-derived fragments (tRFs) are a new class of non-coding RNA that play an important role in regulating cellular RNA processing and protein translation. However, there is currently no study reporting the influence of tRFs on myocardial hypertrophy. In this study, we used an isoproterenol (ISO)-induced myocardial hypertrophy rat model. Small RNA (<40 nts) transcriptome sequencing was used to select differentially expressed tRFs. We also compared the tRFs expression pattern in F0 sperm and the hearts of F1 offspring between the myocardial hypertrophy group (Hyp) and the control group (Con). Isoproterenol successfully induced a typical cardiac hypertrophy model in our study. Small RNA-seq revealed that tRFs were extremely enriched (84%) in the Hyp heart. Overexpression of tRFs1 and tRFs2 both enlarged the surface area of cardiac cells and increased expression of hypertrophic markers (ANF, BNP, and β-MHC). Luciferase reporter assay identified that tRFs1 directly target 3′UTR of Timp3. tRFs1, tRFs2, tRFs3, and tRFs4 were also highly expressed in Hyp F0 sperm and in Hyp F1 offspring hearts, but there was no differential expression of tRFs7, tRFs9, and tRFs10. Compared to Con F1 offspring, Hyp F1 offspring had elevated expression levels of β-MHC and ANP genes, and they had increased fibrosis and apoptosis in their hearts. These results demonstrated that tRFs are involved in regulating the response of myocardial hypertrophy. Besides, tRFs might serve as novel epigenetic factors that contribute to the intergenerational inheritance of cardiac hypertrophy. Full article
(This article belongs to the Special Issue Biomolecules for Translational Approaches in Cardiology)
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Open AccessArticle The Association between Epidermal Growth Factor Receptor (EGFR) Gene Polymorphisms and Lung Cancer Risk
Biomolecules 2018, 8(3), 53; https://doi.org/10.3390/biom8030053
Received: 2 June 2018 / Revised: 7 July 2018 / Accepted: 10 July 2018 / Published: 13 July 2018
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Abstract
Lung cancer is the leading cause of cancer death globally. The epidermal growth factor receptor (EGFR) plays an important role in cell proliferation and signaling. In this study, we examined the association between EGFR gene polymorphisms and lung cancer risk among the Jordanian
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Lung cancer is the leading cause of cancer death globally. The epidermal growth factor receptor (EGFR) plays an important role in cell proliferation and signaling. In this study, we examined the association between EGFR gene polymorphisms and lung cancer risk among the Jordanian population. A total of 129 patients with primary lung cancer and 129 matched healthy controls were recruited into this study. EGFR rs712829, rs712830, rs2072454, and rs11543848 single nucleotide polymorphisms (SNPs) were genotyped to test for their association with lung cancer risk. A significant association was observed between the rs712829 SNP and lung cancer risk (p < 0.05) where the GG + GT genotypes were higher in lung cancer patients when compared to controls. In addition, no association was detected between rs712830, rs2072454, and rs11543848 SNPs and lung cancer risk. When patients were stratified according to the lung cancer type, a significant association was detected between both rs712829 and rs2072454 and adenocarcinoma lung cancer (p < 0.05). Haplotype analysis of all four SNPs showed a significant association between the TCCG haplotype and both lung cancer and the adenocarcinoma subtype (p < 0.001). In conclusion, EGFR rs712829, rs2072454 SNPs, and TCCG haplotypes are associated with a risk of lung cancer among Jordanians. Since genetic associations are affected by the genetic background of populations, more studies in other Arab populations are required to confirm the present findings. Full article
Open AccessArticle Morin as a Preservative for Delaying Senescence of Banana
Biomolecules 2018, 8(3), 52; https://doi.org/10.3390/biom8030052
Received: 19 June 2018 / Revised: 10 July 2018 / Accepted: 10 July 2018 / Published: 12 July 2018
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Abstract
Banana is a climacteric fruit with desirable palatability and high nutritional value. It ripens rapidly accompanied with metabolite changes during postharvest storage. In this work, morin was applied to treat banana to delay senescence. Nuclear magnetic resonance (NMR) spectroscopy was used to monitor
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Banana is a climacteric fruit with desirable palatability and high nutritional value. It ripens rapidly accompanied with metabolite changes during postharvest storage. In this work, morin was applied to treat banana to delay senescence. Nuclear magnetic resonance (NMR) spectroscopy was used to monitor the changes of metabolite composition and levels in banana. The results showed that morin significantly delayed the changes of color and firmness. 1D and 2D NMR spectra reflected that the levels and composition of metabolites were changed with the senescence initiation. The principal component analysis revealed that the first principal components responsible for banana senescence were carbohydrates, amino acids, lipids and phenolics. Morin treatment delayed the transformation of starch to glucose, fructose and sucrose, accelerated the accumulations of alanine and γ-Amino-butyrate (GABA), postponed the generations of valine and l-aspartic acid, suppressed the degradation of saponin a. It indicated that morin was effective in delaying banana senescence. Full article
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Open AccessArticle β-Lactamase Tools for Establishing Cell Internalization and Cytosolic Delivery of Cell Penetrating Peptides
Biomolecules 2018, 8(3), 51; https://doi.org/10.3390/biom8030051
Received: 11 May 2018 / Revised: 22 June 2018 / Accepted: 29 June 2018 / Published: 11 July 2018
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Abstract
The ability of cell penetrating peptides (CPPs) to deliver biologically relevant cargos into cells is becoming more important as targets in the intracellular space continue to be explored. We have developed two assays based on CPP-dependent, intracellular delivery of TEM-1 β-lactamase enzyme, a
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The ability of cell penetrating peptides (CPPs) to deliver biologically relevant cargos into cells is becoming more important as targets in the intracellular space continue to be explored. We have developed two assays based on CPP-dependent, intracellular delivery of TEM-1 β-lactamase enzyme, a functional biological molecule comparable in size to many protein therapeutics. The first assay focuses on the delivery of full-length β-lactamase to evaluate the internalization potential of a CPP sequence. The second assay uses a split-protein system where one component of β-lactamase is constitutively expressed in the cytoplasm of a stable cell line and the other component is delivered by a CPP. The delivery of a split β-lactamase component evaluates the cytosolic delivery capacity of a CPP. We demonstrate that these assays are rapid, flexible and have potential for use with any cell type and CPP sequence. Both assays are validated using canonical and novel CPPs, with limits of detection from <500 nM to 1 µM. Together, the β-lactamase assays provide compatible tools for functional characterization of CPP activity and the delivery of biological cargos into cells. Full article
(This article belongs to the Special Issue Cell Penetrating Peptides)
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Open AccessReview Efficient Delivery of Macromolecules into Human Cells by Improving the Endosomal Escape Activity of Cell-Penetrating Peptides: Lessons Learned from dfTAT and its Analogs
Biomolecules 2018, 8(3), 50; https://doi.org/10.3390/biom8030050
Received: 23 June 2018 / Revised: 5 July 2018 / Accepted: 6 July 2018 / Published: 11 July 2018
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Abstract
Cell-penetrating peptides (CPPs) are typically prone to endocytic uptake into human cells. However, they are often inefficient at escaping from endosomes, which limits their ability to deliver cargos into cells. This review highlights the efforts that our laboratory has devoted toward developing CPPs
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Cell-penetrating peptides (CPPs) are typically prone to endocytic uptake into human cells. However, they are often inefficient at escaping from endosomes, which limits their ability to deliver cargos into cells. This review highlights the efforts that our laboratory has devoted toward developing CPPs that can mediate the leakage of endosomal membranes, and consequently gain better access to the intracellular milieu. In particular, we have identified a CPP named dimeric fluorescent TAT (dfTAT) with high endosomolytic activity. We describe how we have used this reagent and its analogs to develop efficient cytosolic delivery protocols and learn about molecular and cellular parameters that control the cell permeation process. Specifically, we discuss how late endosomes represent exploitable gateways for intracellular entry. We also describe how certain features in CPPs, including guanidinium content, charge density, multimerization, chirality, and susceptibility to degradation modulate the activity that these peptidic agents take toward endosomal membranes and cytosolic egress. Full article
(This article belongs to the Special Issue Cell Penetrating Peptides)
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Open AccessArticle Protein Phosphatase Sit4 Affects Lipid Droplet Synthesis and Soraphen A Resistance Independent of Its Role in Regulating Elongator Dependent tRNA Modification
Biomolecules 2018, 8(3), 49; https://doi.org/10.3390/biom8030049
Received: 4 June 2018 / Revised: 5 July 2018 / Accepted: 9 July 2018 / Published: 11 July 2018
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Abstract
The protein phosphatase Sit4 has been shown to be required for lipogenesis and resistance against the acetyl-CoA carboxylase inhibitor soraphen A. Since Sit4 is also required for biosynthesis of Elongator dependent tRNA modifications such as 5-methoxycarbonylmethyluridine (mcm5U), we investigated the relevance
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The protein phosphatase Sit4 has been shown to be required for lipogenesis and resistance against the acetyl-CoA carboxylase inhibitor soraphen A. Since Sit4 is also required for biosynthesis of Elongator dependent tRNA modifications such as 5-methoxycarbonylmethyluridine (mcm5U), we investigated the relevance of tRNA modifications in lipogenesis and soraphen A response. While sit4 and Elongator (elp3) mutants copy defects in mcm5U formation and stress sensitivity, they do not share soraphen A sensitivity and low lipid droplet (LD) phenotypes. In contrast to sit4, we found elp3 mutants to display partial soraphen A resistance and a high LD phenotype. Screening a collection of tRNA modification mutants additionally identified the tRNA pseudo-uridine synthase gene DEG1 to be required for soraphen A sensitivity. Since deg1 and elp3 share high LD and soraphen A resistance phenotypes, these are likely caused by translational defects. In support of this notion, we observe overexpression of tRNAGlnUUG suppresses lipolysis defects of deg1 mutants. Hence, the sit4 mutation results in a composite defect including tRNA modification deficiency and loss of Snf1 kinase dephosphorylation, which induce opposite effects on LD regulation. Importantly, however, the Snf1 kinase regulatory defects of the phosphatase mutant dominate over effects on LD regulation imposed by loss of the tRNA modification alone. Full article
(This article belongs to the collection RNA Modifications)
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Open AccessArticle A Novel Cell Penetrating Peptide for the Differentiation of Human Neural Stem Cells
Biomolecules 2018, 8(3), 48; https://doi.org/10.3390/biom8030048
Received: 1 May 2018 / Revised: 22 June 2018 / Accepted: 25 June 2018 / Published: 9 July 2018
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Abstract
Retinoic acid (RA) is a bioactive lipid that has been shown to promote neural stem cell differentiation. However, the highly hydrophobic molecule needs to first solubilize and translocate across the cell membrane in order to exert a biological response. The cell entry of
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Retinoic acid (RA) is a bioactive lipid that has been shown to promote neural stem cell differentiation. However, the highly hydrophobic molecule needs to first solubilize and translocate across the cell membrane in order to exert a biological response. The cell entry of RA can be aided by cell penetrating peptides (CPPs), which are short amino acid sequences that are able to carry bioactive cargo past the cell membrane. In this work, a novel cell penetrating peptide was developed to deliver RA to human neural stem cells and, subsequently, promote neuronal differentiation. The novel CPP consists of a repeating sequence, whose number of repeats is proportional to the efficiency of cell penetration. Using fluorescence microscopy, the mode of translocation was determined to be related to an endocytic pathway. The levels of β-III tubulin (Tubb3) and microtubule associated protein 2 (MAP2) expression in neural stem cells treated with RA conjugated to the CPP were assessed by quantitative immunocytochemistry. Full article
(This article belongs to the Special Issue Cell Penetrating Peptides)
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Open AccessCommentary Genetics of Lipodystrophy: Can It Help in Understanding the Pathophysiology of Metabolic Syndrome?
Biomolecules 2018, 8(3), 47; https://doi.org/10.3390/biom8030047
Received: 24 May 2018 / Revised: 21 June 2018 / Accepted: 22 June 2018 / Published: 6 July 2018
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Abstract
Understanding phenotypes and their genetic determinants for metabolic syndrome (MetS) has been quite challenging. With the advent of systems genomic approaches, there is a need to decipher methods for identification and evaluating the functional role of phenotypic traits associated with complex diseases, such
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Understanding phenotypes and their genetic determinants for metabolic syndrome (MetS) has been quite challenging. With the advent of systems genomic approaches, there is a need to decipher methods for identification and evaluating the functional role of phenotypic traits associated with complex diseases, such as MetS. The monogenic syndromes of lipodystrophy are well understood, but the molecular pathophysiology of insulin resistance (IR) underpinning the obesity, diabetes mellitus, and dyslipidemia is not well deciphered. In this commentary, we argue the role of pathophysiology of MetS, and its effects into possible understanding of genetic determinants associated with lipodystrophy-mediated diabetes mellitus. Full article
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Open AccessConference Report ENABLE 2017, the First European PhD and Post-Doc Symposium. Session 1: Building the Foundations of Biology: Synthetic and Cellular Research
Biomolecules 2018, 8(3), 46; https://doi.org/10.3390/biom8030046
Received: 18 June 2018 / Accepted: 20 June 2018 / Published: 6 July 2018
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Abstract
The European Academy for Biomedical Science (ENABLE) is an initiative funded by the European Union Horizon 2020 program involving four renowned European Research Institutes (Institute for Research in Biomedicine—IRB Barcelona, Spain; Radboud Institute for Molecular Life Sciences—RIMLS, the Netherlands; Novo Nordisk Foundation Center
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The European Academy for Biomedical Science (ENABLE) is an initiative funded by the European Union Horizon 2020 program involving four renowned European Research Institutes (Institute for Research in Biomedicine—IRB Barcelona, Spain; Radboud Institute for Molecular Life Sciences—RIMLS, the Netherlands; Novo Nordisk Foundation Center for Protein Research—NNF CPR, Denmark; European School of Molecular Medicine—SEMM, Italy) and an innovative science communication agency (Scienseed). With the aim of promoting biomedical science of excellence in Europe, ENABLE organizes an annual three-day international event. This gathering includes a top-level scientific symposium bringing together leading scientists, PhD students, and post-doctoral fellows; career development activities supporting the progression of young researchers and fostering discussion about opportunities beyond the bench; and outreach activities stimulating the interaction between science and society. The first European PhD and Postdoc Symposium, entitled “Breaking Down Complexity: Innovative Models and Techniques in Biomedicine”, was hosted by the vibrant city of Barcelona. The scientific program of the conference was focused on the most recent advances and applications of modern techniques and models in biomedical research and covered a wide range of topics, from synthetic biology to translational medicine. Overall, the event was a great success, with more than 200 attendees from all over Europe actively participating in the symposium by presenting their research and exchanging ideas with their peers and world-renowned scientists. Full article
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Open AccessReview The Many Faces of Amphipathic Helices
Biomolecules 2018, 8(3), 45; https://doi.org/10.3390/biom8030045
Received: 30 May 2018 / Revised: 2 July 2018 / Accepted: 2 July 2018 / Published: 5 July 2018
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Abstract
Amphipathic helices (AHs), a secondary feature found in many proteins, are defined by their structure and by the segregation of hydrophobic and polar residues between two faces of the helix. This segregation allows AHs to adsorb at polar–apolar interfaces such as the lipid
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Amphipathic helices (AHs), a secondary feature found in many proteins, are defined by their structure and by the segregation of hydrophobic and polar residues between two faces of the helix. This segregation allows AHs to adsorb at polar–apolar interfaces such as the lipid surfaces of cellular organelles. Using various examples, we discuss here how variations within this general scheme impart membrane-interacting AHs with different interfacial properties. Among the key parameters are: (i) the size of hydrophobic residues and their density per helical turn; (ii) the nature, the charge, and the distribution of polar residues; and (iii) the length of the AH. Depending on how these parameters are tuned, AHs can deform lipid bilayers, sense membrane curvature, recognize specific lipids, coat lipid droplets, or protect membranes from stress. Via these diverse mechanisms, AHs play important roles in many cellular processes. Full article
(This article belongs to the Special Issue Cellular Membrane Domains and Organization)
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Open AccessReview A Review of the Recent Advances Made with SIRT6 and its Implications on Aging Related Processes, Major Human Diseases, and Possible Therapeutic Targets
Biomolecules 2018, 8(3), 44; https://doi.org/10.3390/biom8030044
Received: 10 June 2018 / Revised: 24 June 2018 / Accepted: 26 June 2018 / Published: 29 June 2018
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Abstract
Sirtuin 6 (SIRT6) is a nicotinamide adenine dinucleotide+ (NAD+) dependent enzyme and stress response protein that has sparked the curiosity of many researchers in different branches of the biomedical sciences. A unique member of the known Sirtuin family, SIRT6 has
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Sirtuin 6 (SIRT6) is a nicotinamide adenine dinucleotide+ (NAD+) dependent enzyme and stress response protein that has sparked the curiosity of many researchers in different branches of the biomedical sciences. A unique member of the known Sirtuin family, SIRT6 has several different functions in multiple different molecular pathways related to DNA repair, glycolysis, gluconeogenesis, tumorigenesis, neurodegeneration, cardiac hypertrophic responses, and more. Only in recent times, however, did the potential usefulness of SIRT6 come to light as we learned more about its biochemical activity, regulation, biological roles, and structure Frye (2000). Even until very recently, SIRT6 was known more for chromatin signaling but, being a nascent topic of study, more information has been ascertained and its potential involvement in major human diseases including diabetes, cancer, neurodegenerative diseases, and heart disease. It is pivotal to explore the mechanistic workings of SIRT6 since future research may hold the key to engendering strategies involving SIRT6 that may have significant implications for human health and expand upon possible treatment options. In this review, we are primarily concerned with exploring the latest advances in understanding SIRT6 and how it can alter the course of several life-threatening diseases such as processes related to aging, cancer, neurodegenerative diseases, heart disease, and diabetes (SIRT6 has also shown to be involved in liver disease, inflammation, and bone-related issues) and any recent promising pharmacological investigations or potential therapeutics that are of interest. Full article
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Open AccessArticle Prognostic Value of Iron-Homeostasis Regulating Peptide Hepcidin in Coronary Heart Disease—Evidence from the Large AtheroGene Study
Biomolecules 2018, 8(3), 43; https://doi.org/10.3390/biom8030043
Received: 8 June 2018 / Revised: 25 June 2018 / Accepted: 26 June 2018 / Published: 28 June 2018
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Abstract
Iron is essential in terms of oxygen utilization and mitochondrial function. The liver-derived peptide hepcidin has been recognized as a key regulator of iron homeostasis. Since iron metabolism is crucially linked to cardiovascular health, and low hepcidin was proposed as potential new marker
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Iron is essential in terms of oxygen utilization and mitochondrial function. The liver-derived peptide hepcidin has been recognized as a key regulator of iron homeostasis. Since iron metabolism is crucially linked to cardiovascular health, and low hepcidin was proposed as potential new marker of iron metabolism, we aimed to evaluate the prognostic value of hepcidin in a large cohort of patients with coronary heart disease (CHD). Serum levels of hepcidin were determined at baseline in patients with angiographically documented CHD. The main outcome measure was non-fatal myocardial infarction (MI) or cardiovascular death. During a median follow-up of 4.1 years, 10.3% experienced an endpoint. In Cox regression analyses for hepcidin the hazard ratio for future cardiovascular death or MI was 1.03 (95% confidence interval (CI) 0.91–1.18, p = 0.63) after adjustment for sex and age. This association virtually did not change after additional adjustment for body mass index (BMI), smoking status, hypertension, diabetes, dyslipidemia, and surrogates of cardiac function (NT-proBNP), size of myocardial necrosis (troponin I), and anemia (hemoglobin). In this study, by far the largest evaluating the predictive value of hepcidin, hepcidin levels were not associated with future MI or cardiovascular death. This implicates a limited, if any, role for hepcidin in secondary cardiovascular risk prediction. Full article
(This article belongs to the Special Issue Biomolecules for Translational Approaches in Cardiology)
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