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Open AccessArticle
The Effects of a Novel Series of KTTKS Analogues on Cytotoxicity and Proteolytic Activity
Molecules 2019, 24(20), 3698; https://doi.org/10.3390/molecules24203698 (registering DOI) - 15 Oct 2019
Abstract
KTTKS is a matrikine that originates from the proteolytic hydrolysis of collagen. This peptide stimulates ECM production and types I and III collagen expression in vitro. A more stable form of KTTKS is pal-KTTKS, known as Matrixyl® or palmitoyl pentapeptide-3. A series [...] Read more.
KTTKS is a matrikine that originates from the proteolytic hydrolysis of collagen. This peptide stimulates ECM production and types I and III collagen expression in vitro. A more stable form of KTTKS is pal-KTTKS, known as Matrixyl® or palmitoyl pentapeptide-3. A series of novel pentapeptides, analogues of KTTKS with the general formula X-KTTKS-OH(NH2), where X = acetyl, lipoyl, palmitoyl residues, was designed and synthesized. Their effect on amidolytic activity of urokinase, thrombin, trypsin, plasmin, t-PA, and kallikrein were tested. Cytotoxic tests on fibroblasts, as well as collagen and DNA biosynthesis tests for selected peptides, were also carried out. The test results showed that the most active plasmin inhibitors were palmitoyl peptides, whether in acid or amide form. No biological effects of lysine modification to arginine in the synthesized peptides were found. None of the synthesized peptides was not cytotoxic on fibroblasts, and three of them showed cell growth. These three compounds showed no concentration-activity relationship in the collagen and DNA biosynthesis assays. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessArticle
A Pan-Cancer Approach to Predict Responsiveness to Immune Checkpoint Inhibitors by Machine Learning
Cancers 2019, 11(10), 1562; https://doi.org/10.3390/cancers11101562 (registering DOI) - 15 Oct 2019
Abstract
Immunotherapy by using immune checkpoint inhibitors (ICI) has dramatically improved the treatment options in various cancers, increasing survival rates for treated patients. Nevertheless, there are heterogeneous response rates to ICI among different cancer types, and even in the context of patients affected by [...] Read more.
Immunotherapy by using immune checkpoint inhibitors (ICI) has dramatically improved the treatment options in various cancers, increasing survival rates for treated patients. Nevertheless, there are heterogeneous response rates to ICI among different cancer types, and even in the context of patients affected by a specific cancer. Thus, it becomes crucial to identify factors that predict the response to immunotherapeutic approaches. A comprehensive investigation of the mutational and immunological aspects of the tumor can be useful to obtain a robust prediction. By performing a pan-cancer analysis on gene expression data from the Cancer Genome Atlas (TCGA, 8055 cases and 29 cancer types), we set up and validated a machine learning approach to predict the potential for positive response to ICI. Support vector machines (SVM) and extreme gradient boosting (XGboost) models were developed with a 10×5-fold cross-validation schema on 80% of TCGA cases to predict ICI responsiveness defined by a score combining tumor mutational burden and TGF- β signaling. On the remaining 20% validation subset, our SVM model scored 0.88 accuracy and 0.27 Matthews Correlation Coefficient. The proposed machine learning approach could be useful to predict the putative response to ICI treatment by expression data of primary tumors. Full article
(This article belongs to the Special Issue Application of Next-Generation Sequencing in Cancers)
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Open AccessArticle
Size and Shape-Dependent Solubility of CuO Nanostructures
Materials 2019, 12(20), 3355; https://doi.org/10.3390/ma12203355 (registering DOI) - 15 Oct 2019
Abstract
In our theoretical study, the enhanced solubility of CuO nanoparticles in water saturated by air is predicted based on a simple thermodynamic model. CuO is considered in the form of nanoparticles with various shapes. The interfacial energy of a solid CuO/dilute aqueous solution [...] Read more.
In our theoretical study, the enhanced solubility of CuO nanoparticles in water saturated by air is predicted based on a simple thermodynamic model. CuO is considered in the form of nanoparticles with various shapes. The interfacial energy of a solid CuO/dilute aqueous solution interface was assessed by applying the average CuO surface energy and contact angle of a sessile drop of water. The equilibrium CuO solubility was calculated using Gibbs energy minimization technique. For the smallest spherical nanoparticles considered in this work (r = 2 nm), the solubility is significantly higher than the solubility of bulk material. In the case of cylindrical nanoparticles, the solubility increase is even more considerable. The CuO spherical nanoparticles solubility was also calculated using the Ostwald–Freundlich equation which is known to overestimate the solubility as discussed in this contribution. Full article
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Open AccessArticle
Antimalarial Properties of Dunnione Derivatives as NQO2 Substrates
Molecules 2019, 24(20), 3697; https://doi.org/10.3390/molecules24203697 (registering DOI) - 15 Oct 2019
Abstract
Dunnione, a natural product isolated from the leaves of Streptocarpus dunnii (Gesneriaceae), acts as a substrate for quinone-reductases that may be associated with its antimalarial properties. Following our exploration of reactive oxygen species-producing compounds such as indolones, as possible new approaches for the [...] Read more.
Dunnione, a natural product isolated from the leaves of Streptocarpus dunnii (Gesneriaceae), acts as a substrate for quinone-reductases that may be associated with its antimalarial properties. Following our exploration of reactive oxygen species-producing compounds such as indolones, as possible new approaches for the research of new ways to treat this parasitosis, we explored derivatives of this natural product and their possible antiplasmodial and antimalarial properties, in vitro and in vivo, respectively. Apart from one compound, all the products tested had weak to moderate antiplasmodial activities, the best IC50 value being equal to 0.58 µM. In vivo activities in the murine model were moderate (at a dose of 50 mg/kg/mice, five times higher than the dose of chloroquine). These results encourage further pharmacomodulation steps to improve the targeting of the parasitized red blood cells and antimalarial activities. Full article
(This article belongs to the Section Medicinal Chemistry)
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Open AccessFeature PaperArticle
Comparison of Multivariate Regression Models Based on Water- and Carbohydrate-Related Spectral Regions in the Near-Infrared for Aqueous Solutions of Glucose
Molecules 2019, 24(20), 3696; https://doi.org/10.3390/molecules24203696 (registering DOI) - 15 Oct 2019
Abstract
The predictive power of the two major water bands centered at 6900 cm-1 and 5200 cm-1 in the near-infrared (NIR) region was compared to carbohydrate-related spectral areas located in the first overtone (around 6000 cm-1) and [...] Read more.
The predictive power of the two major water bands centered at 6900 cm - 1 and 5200 cm - 1 in the near-infrared (NIR) region was compared to carbohydrate-related spectral areas located in the first overtone (around 6000 cm - 1 ) and combination (around 4500 cm - 1 ) region using glucose in aqueous solutions as a model substance. For the purpose of optimal coverage of stronger as well as weaker absorbing NIR regions, cells with three different declared optical pathlengths were employed. The sample set consisted of multiple separately prepared batches in the range of 50–200 mmol/L. Moreover, the samples were divided into a calibration set for the construction of the partial least squares regression (PLS-R) models and a test set for the validation process with independent samples. The first overtone and combination region showed relative prediction errors between 0.4–1.6% with only one PLS-R factor required. On the other hand, the errors for the water bands were found between 1.6–8.3% and up to three PLS-R factors required. The best PLS-R models resulted from the cell with 1 mm optical pathlength. In general, the results suggested that the carbohydrate-related regions in the first overtone and combination region should be preferred over the regions of the two dominant water bands. Full article
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Open AccessArticle
Exploring Epidemiological Characteristics of Domestic Imported Dengue Fever in Mainland China, 2014–2018
Int. J. Environ. Res. Public Health 2019, 16(20), 3901; https://doi.org/10.3390/ijerph16203901 (registering DOI) - 15 Oct 2019
Abstract
Epidemiological characteristics of domestic imported dengue fever in mainland China, 2014–2018, including time-series, spatial mobility and crowd features, were analyzed. There existed seasonal characteristics from August to November. The 872 domestic imported cases from 8 provinces, located in the southeastern, southwestern and southern [...] Read more.
Epidemiological characteristics of domestic imported dengue fever in mainland China, 2014–2018, including time-series, spatial mobility and crowd features, were analyzed. There existed seasonal characteristics from August to November. The 872 domestic imported cases from 8 provinces, located in the southeastern, southwestern and southern coastal or border areas, were imported to 267 counties in 20 provinces of mainland China, located in the outer areas along the southwest-northeast line. The 628 domestic imported cases were still imported to the adjacent counties in the provinces themselves, 234 domestic imported cases were imported to 12 other provinces except the 8 original exported provinces, 493 cases in 2014 reached the peak, and 816 domestic imported cases were from Guangdong (675) and Yunnan (141). Domestic imported cases from Guangdong were imported to 218 counties, and 475 cases from Guangdong were imported to the adjacent counties in Guangdong itself. There were more male cases than female cases except in 2016. Domestic imported cases were clustered from 21 to 50 years old. The top three cases were from farmer, worker and housework or unemployed. The findings are helpful to formulate targeted, strategic plans and implement effective public health prevention and control measures. Full article
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Open AccessFeature PaperArticle
Quantitative Immunomorphological Analysis of Heat Shock Proteins in Thyroid Follicular Adenoma and Carcinoma Tissues Reveals Their Potential for Differential Diagnosis and Points to a Role in Carcinogenesis
Appl. Sci. 2019, 9(20), 4324; https://doi.org/10.3390/app9204324 (registering DOI) - 15 Oct 2019
Abstract
Hsp27, Hsp60, Hsp70, and Hsp90 are chaperones that play a crucial role in cellular homeostasis and differentiation, but they may be implicated in carcinogenesis. Follicular neoplasms of the thyroid include follicular adenoma and follicular carcinoma. The former is a very frequent benign encapsulated [...] Read more.
Hsp27, Hsp60, Hsp70, and Hsp90 are chaperones that play a crucial role in cellular homeostasis and differentiation, but they may be implicated in carcinogenesis. Follicular neoplasms of the thyroid include follicular adenoma and follicular carcinoma. The former is a very frequent benign encapsulated nodule, whereas the other is a nodule that infiltrates the capsule, blood vessels and the adjacent parenchyma, with a tendency to metastasize. The main objective was to assess the potential of the Hsps in differential diagnosis and carcinogenesis. We quantified by immunohistochemistry Hsp27, Hsp60, Hsp70, and Hsp90 on thin sections of human thyroid tissue with follicular adenoma or follicular carcinoma, comparing the tumor with the adjacent peritumoral tissue. Hsp60, Hsp70, and Hsp90 were increased in follicular carcinoma compared to follicular adenoma, while Hsp27 showed no difference. Histochemical quantification of Hsp60, Hsp70, and Hsp90 allows diagnostic distinction between follicular adenoma and carcinoma, and between tumor and adjacent non-tumoral tissue. The quantitative variations of these chaperones in follicular carcinoma suggest their involvement in tumorigenesis, for instance in processes such as invasion of thyroid parenchyma and metastasization. Full article
(This article belongs to the Special Issue Immunohistochemical Expression)
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Open AccessBrief Report
Antioxidant Saffron and Central Retinal Function in ABCA4-Related Stargardt Macular Dystrophy
Nutrients 2019, 11(10), 2461; https://doi.org/10.3390/nu11102461 (registering DOI) - 15 Oct 2019
Abstract
Retinal oxidative damage, associated with an ATP-binding cassette, sub-family A, member 4, also known as ABCA4 gene mutation, has been implicated as a major underlying mechanism for Stargardt disease/fundus flavimaculatus (STG/FF). Recent findings indicate that saffron carotenoid constituents crocins and crocetin may counteract [...] Read more.
Retinal oxidative damage, associated with an ATP-binding cassette, sub-family A, member 4, also known as ABCA4 gene mutation, has been implicated as a major underlying mechanism for Stargardt disease/fundus flavimaculatus (STG/FF). Recent findings indicate that saffron carotenoid constituents crocins and crocetin may counteract retinal oxidative damage, inflammation and protect retinal cells from apoptosis. This pilot study aimed to evaluate central retinal function following saffron supplementation in STG/FF patients carrying ABCA4 mutations. Methods: in a randomized, double-blind, placebo-controlled study (clinicaltrials.gov: NCT01278277), 31 patients with ABCA4-related STG/FF and a visual acuity >0.25 were randomly assigned to assume oral saffron (20 mg) or placebo over a six month period and then reverted to P or S for a further six month period. Full ophthalmic examinations, as well as central 18° focal electroretinogram (fERG) recordings, were performed at baseline and after six months of either saffron or placebo. The fERG fundamental harmonic component was isolated by Fourier analysis. Main outcome measures were fERG amplitude (in µV) and phase (in degrees). The secondary outcome measure was visual acuity. Results: supplement was well tolerated by all patients throughout follow-up. After saffron, fERG amplitude was unchanged; after placebo, amplitude tended to decrease from baseline (mean change: −0.18 log µV, p < 0.05). Reverting the treatments, amplitude did not change significantly. fERG phase and visual acuity were unchanged throughout follow-up. Conclusions: short-term saffron supplementation was well tolerated and had no detrimental effects on the electroretinographic responses of the central retina and visual acuity. The current findings warrant further long-term clinical trials to assess the efficacy of saffron supplementation in slowing down the progression of central retinal dysfunction in ABCA4-related STG/FF. Full article
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Open AccessArticle
Blending Insights from Implementation Science and the Social Sciences to Mitigate Inequities in Screening for Hereditary Cancer Syndromes
Int. J. Environ. Res. Public Health 2019, 16(20), 3899; https://doi.org/10.3390/ijerph16203899 (registering DOI) - 15 Oct 2019
Abstract
Genomic screening to identify people at high risk for adult-onset hereditary conditions has potential to improve population health. However, if not equitably accessible, genomics-informed screening programs will exacerbate existing health inequities or give rise to new ones. To realize the disease prevention potential [...] Read more.
Genomic screening to identify people at high risk for adult-onset hereditary conditions has potential to improve population health. However, if not equitably accessible, genomics-informed screening programs will exacerbate existing health inequities or give rise to new ones. To realize the disease prevention potential of these screening tools, we need strategies to broaden their reach. We propose a conceptual framework that merges insights from implementation science and sociological research on health inequities. Our framework does three things: first, it broadens the arenas of action beyond those typically addressed in implementation science frameworks; second, it argues for recruiting more diverse partners to share the work of implementation and dissemination; and third, it shows how implementation activities can be coordinated more effectively among those partners. We use screening for hereditary breast and ovarian cancers (HBOC) as a case to illustrate how this enhanced framework could guide implementation science and distribute the benefits of genomic medicine more equitably. Although our example is specific to genomics, this approach is more broadly applicable to the field of implementation science. Coordinated action among multiple stakeholders could translate a host of new technologies from the bench to the trench without creating new inequities or exacerbating existing ones. Full article
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Open AccessArticle
Efficient Removal of Butachlor and Change in Microbial Community Structure in Single-Chamber Microbial Fuel Cells
Int. J. Environ. Res. Public Health 2019, 16(20), 3897; https://doi.org/10.3390/ijerph16203897 (registering DOI) - 15 Oct 2019
Abstract
Microbial electrochemical technology provides an inexhaustible supply of electron acceptors, allowing electroactive microorganisms to generate biocurrent and accelerate the removal of organics. The treatment of wastewater contaminated by butachlor, which is a commonly used chloroacetamide herbicide in paddy fields, is a problem in [...] Read more.
Microbial electrochemical technology provides an inexhaustible supply of electron acceptors, allowing electroactive microorganisms to generate biocurrent and accelerate the removal of organics. The treatment of wastewater contaminated by butachlor, which is a commonly used chloroacetamide herbicide in paddy fields, is a problem in agricultural production. In this study, butachlor was found to be removed efficiently (90 ± 1%) and rapidly (one day) in constructed single-chamber microbial fuel cells (MFCs). After the addition of sodium acetate to MFCs with butachlor as the sole carbon source, electricity generation was recovered instead of increasing the degradation efficiency of butachlor. Meanwhile, the microbial community structure was changed in anodic and cathodic biofilms after the addition of butachlor, following the bioelectrochemical degradation of butachlor. High-throughput sequencing showed the proliferation of Paracoccus and Geobacter in MFCs with butachlor as the sole carbon source and of Thauera butanivorans in MFCs with butachlor and sodium acetate as concomitant carbon sources. These species possess the ability to oxidize different substituents of butachlor and have important potential use for the bioremediation of wastewater, sediments, and soils. Full article
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Open AccessEditorial
Remote Sensing of Urban Forests
Remote Sens. 2019, 11(20), 2383; https://doi.org/10.3390/rs11202383 (registering DOI) - 15 Oct 2019
Abstract
Urban forests and green infrastructures at large are of critical importance for contemporary cities as they provide a wide range of ecosystem services (ESS) that enhance the quality of life of urban dwellers. Remote sensing technologies have greatly contributed to assessing and mapping [...] Read more.
Urban forests and green infrastructures at large are of critical importance for contemporary cities as they provide a wide range of ecosystem services (ESS) that enhance the quality of life of urban dwellers. Remote sensing technologies have greatly contributed to assessing and mapping the spatial distribution of ESS in urban areas, although more research is needed given the availability of new sensors from multiple satellites and platforms and the particular characteristics of urban environments (e.g., high heterogeneity). This Special Issue hosts papers focusing on the temporal and spatial dynamics of urban forests with special attention given to the most recent remote sensing technologies as well as advanced methods for processing geospatial data and extracting meaningful information. Full article
(This article belongs to the Special Issue Remote Sensing of Urban Forests)
Open AccessAbstract
Novel Formulations of PEG–Silica Phase-Changing Materials (PCMs) with Applications in Passive Storage of Thermal Energy
Proceedings 2019, 29(1), 75; https://doi.org/10.3390/proceedings2019029075 (registering DOI) - 15 Oct 2019
Abstract
The aim of the present study is to design new PEG–silica hybrids (PEGx–Si) as phase changing [...] Full article
Open AccessArticle
Agreement between Fathers’ and Mothers’ Reported Stimulation and Associations with Observed Responsive Parenting in Pakistan
Children 2019, 6(10), 114; https://doi.org/10.3390/children6100114 (registering DOI) - 15 Oct 2019
Abstract
Parental stimulation and responsiveness are associated with improved early child development outcomes. However, the majority of studies have relied on maternal-reported measures of only mothers’ parenting practices. The purpose of this study was to assess the agreement between fathers’ and mothers’ reports of [...] Read more.
Parental stimulation and responsiveness are associated with improved early child development outcomes. However, the majority of studies have relied on maternal-reported measures of only mothers’ parenting practices. The purpose of this study was to assess the agreement between fathers’ and mothers’ reports of their own and their partner’s engagement in stimulation and assess the degree to which parents’ reported stimulation correlated with their observed responsive caregiving behaviors. Data were collected from 33 couples (33 fathers and 32 mothers) who had a child under 5 years of age in rural Pakistan. Paternal and maternal stimulation were measured based on reports of their own and their partner’s practices in play and learning activities with the child. Paternal and maternal responsiveness were observed in a subsample of 18 families. Moderate agreement was found between paternal and maternal reports of their own and their partner’s practices. Moderate associations were also found between self-reported measures of stimulation and observed responsive caregiving for both fathers and mothers. The strengths of agreement and associations were greater among couples who had higher quality coparenting relationships. Findings highlight the feasibility, reliability, and promise of assessing fathers’ parenting in a low-resource setting, using similar methods as for mothers’ parenting, to triangulate measures between reported and observed parenting and gain a deeper understanding of fathers’ and mothers’ unique caregiving contributions. Full article
(This article belongs to the Section Global and Public Health)
Open AccessReview
Prion Protein in Glioblastoma Multiforme
Int. J. Mol. Sci. 2019, 20(20), 5107; https://doi.org/10.3390/ijms20205107 (registering DOI) - 15 Oct 2019
Abstract
The cellular prion protein (PrPc) is an evolutionarily conserved cell surface protein encoded by the PRNP gene. PrPc is ubiquitously expressed within nearly all mammalian cells, though most abundantly within the CNS. Besides being implicated in the pathogenesis and transmission of prion diseases, [...] Read more.
The cellular prion protein (PrPc) is an evolutionarily conserved cell surface protein encoded by the PRNP gene. PrPc is ubiquitously expressed within nearly all mammalian cells, though most abundantly within the CNS. Besides being implicated in the pathogenesis and transmission of prion diseases, recent studies have demonstrated that PrPc contributes to tumorigenesis by regulating tumor growth, differentiation, and resistance to conventional therapies. In particular, PrPc over-expression has been related to the acquisition of a malignant phenotype of cancer stem cells (CSCs) in a variety of solid tumors, encompassing pancreatic ductal adenocarcinoma (PDAC), osteosarcoma, breast cancer, gastric cancer, and primary brain tumors, mostly glioblastoma multiforme (GBM). Thus, PrPc is emerging as a key in maintaining glioblastoma cancer stem cells’ (GSCs) phenotype, thereby strongly affecting GBM infiltration and relapse. In fact, PrPc contributes to GSCs niche’s maintenance by modulating GSCs’ stem cell-like properties while restraining them from differentiation. This is the first review that discusses the role of PrPc in GBM. The manuscript focuses on how PrPc may act on GSCs to modify their expression and translational profile while making the micro-environment surrounding the GSCs niche more favorable to GBM growth and infiltration. Full article
(This article belongs to the Special Issue Molecular Biology of Brain Tumors)
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Open AccessExtended Abstract
Preparation and Characterization of Vegetable Oil-Based Microemulsions
Proceedings 2019, 29(1), 74; https://doi.org/10.3390/proceedings2019029074 (registering DOI) - 15 Oct 2019
Abstract
Microemulsions are thermodynamically stable and transparent systems composed of an aqueous phase, oil, a surfactant, and usually also contain a co-surfactant [1]. [...] Full article

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