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Biomolecules, Volume 10, Issue 5 (May 2020) – 148 articles

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Cover Story (view full-size image) β-Lactamase inhibitors (BLIs) are used in combination with existing β-lactam antibiotics to [...] Read more.
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Open AccessArticle
Hindering of Cariogenic Streptococcus mutans Biofilm by Fatty Acid Array Derived from an Endophytic Arthrographis kalrae Strain
Biomolecules 2020, 10(5), 811; https://doi.org/10.3390/biom10050811 - 25 May 2020
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Abstract
Streptococcus mutans has been considered as the major etiological agent of dental caries, mostly due to its arsenal of virulence factors, including strong biofilm formation, exopolysaccharides production, and high acid production. Here, we present the antivirulence activity of fatty acids derived from the [...] Read more.
Streptococcus mutans has been considered as the major etiological agent of dental caries, mostly due to its arsenal of virulence factors, including strong biofilm formation, exopolysaccharides production, and high acid production. Here, we present the antivirulence activity of fatty acids derived from the endophytic fungus Arthrographis kalrae isolated from Coriandrum sativum against Streptococcus mutans. The chemical composition of the fatty acids was analyzed by gas chromatography–mass spectrometry GC-MS and revealed nine compounds representing 99.6% of fatty acids, where unsaturated and saturated fatty acids formed 93.8% and 5.8 % respectively. Oleic and linoleic acids were the major unsaturated fatty acids. Noteworthy, the fatty acids at the concentration of 31.3 mg L–1 completely inhibited Streptococcus mutans biofilm, and water insoluble extracellular polysaccharide production in both polystyrene plates, and tooth model assay using saliva-coated hydroxyapatite discs. Inhibition of biofilm correlated significantly and positively with the inhibition of water insoluble extracellular polysaccharide (R = 1, p < 0.0001). Furthermore, Arthrographis kalrae fatty acids at a concentration of 7.8 mg L–1 exhibited acidogenesis-mitigation activity. They did not show bactericidal activity against Streptococcus mutans and cytotoxic activity against human oral fibroblast cells at the concentration used. On the other hand, saliva-coated hydroxyapatite discs treated with sub-minimum biofilm inhibitory concentration of fatty acids showed disturbed biofilm architecture with a few unequally distributed clumped matrices using fluorescence microscopy. Our findings revealed that the intracellular fatty acid arrays derived from endophytic Arthrographis kalrae could contribute to the biofilm-preventing alternatives, specifically Streptococcus mutans biofilms. Full article
(This article belongs to the Section Natural and Bio-inspired Molecules)
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Open AccessArticle
Reduced Reverse Cholesterol Transport Efficacy in Healthy Men with Undesirable Postprandial Triglyceride Response
Biomolecules 2020, 10(5), 810; https://doi.org/10.3390/biom10050810 - 25 May 2020
Viewed by 231
Abstract
Elevation of nonfasting triglyceride (TG) levels above 1.8 g/L (2 mmol/L) is associated with increased risk of cardiovascular diseases. Exacerbated postprandial hypertriglyceridemia (PP–HTG) and metabolic context both modulate the overall efficacy of the reverse cholesterol transport (RCT) pathway, but the specific contribution of [...] Read more.
Elevation of nonfasting triglyceride (TG) levels above 1.8 g/L (2 mmol/L) is associated with increased risk of cardiovascular diseases. Exacerbated postprandial hypertriglyceridemia (PP–HTG) and metabolic context both modulate the overall efficacy of the reverse cholesterol transport (RCT) pathway, but the specific contribution of exaggerated PP–HTG on RCT efficacy remains indeterminate. Healthy male volunteers (n = 78) exhibiting no clinical features of metabolic disorders underwent a postprandial exploration following consumption of a typical Western meal providing 1200 kcal. Subjects were stratified according to maximal nonfasting TG levels reached after ingestion of the test meal into subjects with a desirable PP–TG response (GLow, TG < 1.8 g/L, n = 47) and subjects with an undesirable PP–TG response (GHigh, TG > 1.8 g/L, n = 31). The impact of the degree of PP–TG response on major steps of RCT pathway, including cholesterol efflux from human macrophages, cholesteryl ester transfer protein (CETP) activity, and hepatic high-density lipoprotein (HDL)-cholesteryl ester (CE) selective uptake, was evaluated. Cholesterol efflux from human macrophages was not significantly affected by the degree of the PP–TG response. Postprandial increase in CETP-mediated CE transfer from HDL to triglyceride-rich lipoprotein particles, and more specifically to chylomicrons, was enhanced in GHigh vs. GLow. The hepatic HDL-CE delivery was reduced in subjects from GHigh in comparison with those from GLow. Undesirable PP–TG response induces an overall reduction in RCT efficacy that contributes to the onset elevation of both fasting and nonfasting TG levels and to the development of cardiometabolic diseases. Full article
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Open AccessReview
Trehalose for Ocular Surface Health
Biomolecules 2020, 10(5), 809; https://doi.org/10.3390/biom10050809 - 25 May 2020
Viewed by 179
Abstract
Trehalose is a natural disaccharide synthesized in various life forms, but not found in vertebrates. An increasing body of evidence demonstrates exceptional bioprotective characteristics of trehalose. This review discusses the scientific findings on potential functions of trehalose in oxidative stress, protein clearance, and [...] Read more.
Trehalose is a natural disaccharide synthesized in various life forms, but not found in vertebrates. An increasing body of evidence demonstrates exceptional bioprotective characteristics of trehalose. This review discusses the scientific findings on potential functions of trehalose in oxidative stress, protein clearance, and inflammation, with an emphasis on animal models and clinical trials in ophthalmology. The main objective is to help understand the beneficial effects of trehalose in clinical trials and practice, especially in patients suffering from ocular surface disease. The discussion is supplemented with an overview of patents for the use of trehalose in dry eye and with prospects for the 2020s. Full article
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Open AccessArticle
Novel Barbiturate-Nitrate Compounds Inhibit the Upregulation of Matrix Metalloproteinase-9 Gene Expression in Intestinal Inflammation through a cGMP-Mediated Pathway
Biomolecules 2020, 10(5), 808; https://doi.org/10.3390/biom10050808 - 25 May 2020
Viewed by 195
Abstract
Matrix metalloproteinase-9 is upregulated in inflammatory bowel disease. Barbiturate nitrate hybrid compounds have been designed to inhibit MMP secretion and enzyme activity. In this study, we investigated the mechanism of action of barbiturate-nitrate hybrid compounds and their component parts using models of intestinal [...] Read more.
Matrix metalloproteinase-9 is upregulated in inflammatory bowel disease. Barbiturate nitrate hybrid compounds have been designed to inhibit MMP secretion and enzyme activity. In this study, we investigated the mechanism of action of barbiturate-nitrate hybrid compounds and their component parts using models of intestinal inflammation in vitro. Cytokine-stimulated Caco-2 cells were used in all in vitro experiments. The NO donors SNAP and DETA-NONOate were used to study the effect of NO on MMP-9 mRNA. Mechanistic elucidation was carried out using the soluble guanylate cyclase (sGC) inhibitor, ODQ, and the cGMP analogue, 8-Bromo-cGMP. Further experiments were carried out to elucidate the role of NF-κB. NO donors exerted an inhibitory effect on MMP-9 mRNA in cytokine-stimulated cells. While the non-nitrate barbiturates had a limited effect on MMP-9 expression, the hybrid compounds inhibited MMP-9 expression through its NO-mimetic properties. No effect could be observed on mRNA for MMP-1 or MMP-2. The sGC inhibitior, ODQ, abolished the nitrate-barbiturate inhibition of MMP-9 gene expression, an effect which was reversed by 8-Br-cGMP. This study shows that the barbiturate scaffold is suitable for hybrid design as an MMP-9 inhibitor in cytokine-stimulated Caco-2 cells. The inhibition of MMP-9 levels was largely mediated through a reduction in its mRNA by a sGC/cGMP pathway mediated mechanism. Full article
(This article belongs to the Special Issue Matrix Metalloproteinases in Health and Disease)
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Open AccessArticle
ATBF1 Participates in Dual Functions of TGF-β via Regulation of Gene Expression and Protein Translocalization
Biomolecules 2020, 10(5), 807; https://doi.org/10.3390/biom10050807 - 24 May 2020
Viewed by 262
Abstract
TGF-β is a critical cytokine to regulate multiple pathophysiological functions. For tumor development and progression, TGF-β was reported to play dual functions as a tumor suppressor and epithelial-mesenchymal transition (EMT) inducer. The mechanism of the TGF-β signaling pathway is essential for TGF-β/Smad-targeted therapy [...] Read more.
TGF-β is a critical cytokine to regulate multiple pathophysiological functions. For tumor development and progression, TGF-β was reported to play dual functions as a tumor suppressor and epithelial-mesenchymal transition (EMT) inducer. The mechanism of the TGF-β signaling pathway is essential for TGF-β/Smad-targeted therapy in clinic. Here, ATBF1 was demonstrated to participate in dual functions of TGF-β via different ways. On one hand, ATBF1 expression level was associated with EMT and migration induced by TGF-β. After TGF-β treatment, ATBF1 expression was reduced in a dose- and time-dependent manner, along with the alteration of cell morphology and EMT marker expression. Knockdown of ATBF1 by siRNA further promoted EMT progression and cell migration. On the other hand, ATBF1 localization was associated with cell proliferation inhibited by TGF-β. The number of cells with nucleus localization of ATBF1 in TGF-β activation group was much higher than that in control group. After that, knockdown of ATBF1 by siRNA rescued the inhibition of cell proliferation affected by TGF-β. These data revealed that ATBF1 is a key gene for the dual roles of TGF-β, which may contribute to future therapy. Full article
(This article belongs to the Special Issue The Biology of Cell Metastasis)
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Open AccessArticle
Enhanced Biomass Yield of and Saccharification in Transgenic Tobacco Over-Expressing β-Glucosidase
Biomolecules 2020, 10(5), 806; https://doi.org/10.3390/biom10050806 - 23 May 2020
Viewed by 229
Abstract
Here, we report an increase in biomass yield and saccharification in transgenic tobacco plants (Nicotiana tabacum L.) overexpressing thermostable β-glucosidase from Thermotoga maritima, BglB, targeted to the chloroplasts and vacuoles. The transgenic tobacco plants showed phenotypic characteristics that were [...] Read more.
Here, we report an increase in biomass yield and saccharification in transgenic tobacco plants (Nicotiana tabacum L.) overexpressing thermostable β-glucosidase from Thermotoga maritima, BglB, targeted to the chloroplasts and vacuoles. The transgenic tobacco plants showed phenotypic characteristics that were significantly different from those of the wild-type plants. The biomass yield and life cycle (from germination to flowering and harvest) of the transgenic tobacco plants overexpressing BglB were 52% higher and 36% shorter than those of the wild-type tobacco plants, respectively, indicating a change in the genome transcription levels in the transgenic tobacco plants. Saccharification in biomass samples from the transgenic tobacco plants was 92% higher than that in biomass samples from the wild-type tobacco plants. The transgenic tobacco plants required a total investment (US$/year) corresponding to 52.9% of that required for the wild-type tobacco plants, but the total biomass yield (kg/year) of the transgenic tobacco plants was 43% higher than that of the wild-type tobacco plants. This approach could be applied to other plants to increase biomass yields and overproduce β-glucosidase for lignocellulose conversion. Full article
(This article belongs to the Section Natural and Bio-inspired Molecules)
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Open AccessArticle
Viridistratins A−C, Antimicrobial and Cytotoxic Benzo[j]fluoranthenes from Stromata of Annulohypoxylon viridistratum (Hypoxylaceae, Ascomycota)
Biomolecules 2020, 10(5), 805; https://doi.org/10.3390/biom10050805 - 23 May 2020
Viewed by 337
Abstract
During the course of our search for novel biologically active metabolites from tropical fungi, we are using chemotaxonomic and taxonomic methodology for the preselection of interesting materials. Recently, three previously undescribed benzo[j]fluoranthenes (13) together with the known [...] Read more.
During the course of our search for novel biologically active metabolites from tropical fungi, we are using chemotaxonomic and taxonomic methodology for the preselection of interesting materials. Recently, three previously undescribed benzo[j]fluoranthenes (13) together with the known derivatives truncatones A and C (4, 5) were isolated from the stromata of the recently described species Annulohypoxylon viridistratum collected in Thailand. Their chemical structures were elucidated by means of spectral methods, including nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). The new compounds, for which we propose the trivial names viridistratins A−C, exhibited weak-to-moderate antimicrobial and cytotoxic activities in cell-based assays. Full article
(This article belongs to the Special Issue 2020 Feature Papers by Biomolecules’ Editorial Board Members)
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Open AccessArticle
Structure of O-Polysaccharide and Lipid A of Pantoea Agglomerans 8488
Biomolecules 2020, 10(5), 804; https://doi.org/10.3390/biom10050804 - 22 May 2020
Viewed by 252
Abstract
The Pantoea agglomerans 8488 lipopolysaccharide (LPS) was isolated, purified and characterized by monosaccharide and fatty acid analysis. The O-polysaccharide and lipid A components of the LPS were separated by mild acid degradation. Lipid A was studied by electrospray ionization mass spectrometry (ESI-MS) and [...] Read more.
The Pantoea agglomerans 8488 lipopolysaccharide (LPS) was isolated, purified and characterized by monosaccharide and fatty acid analysis. The O-polysaccharide and lipid A components of the LPS were separated by mild acid degradation. Lipid A was studied by electrospray ionization mass spectrometry (ESI-MS) and found to consist of hexa-, penta-, tetra- and tri-acylated species. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy revealed the following structure of the O-polysaccharide repeating unit →3)-α-L-Rhap-(1→6)-α-D-Manp-(1→3)-α-L-Fucp-(1→3)-β-D-GlcNAcp-(1→. The LPS showed a low level of toxicity, was not pyrogenic, and reduced the adhesiveness index of microorganisms to 2.12, which was twofold less than the control. LPS modified by complex compounds of germanium (IV) and tin (IV) were obtained. It was found that six LPS samples modified by Sn compounds and two LPS samples modified by Ge compounds lost their toxic activity when administered to mice in a dose of LD50 (105 µg/mice or 5 mg/kg). However, none of the modified LPS samples changed their serological activity in an Ouchterlony double immunodiffusion test in agar. Full article
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Open AccessArticle
Hemp (Cannabis sativa L.) Protein Hydrolysates Promote Anti-Inflammatory Response in Primary Human Monocytes
Biomolecules 2020, 10(5), 803; https://doi.org/10.3390/biom10050803 - 22 May 2020
Viewed by 229
Abstract
Hemp seeds have a wide variety of chemical compounds which present biological activity. Specifically, the focus on proteins and bioactive peptides are increasing as alternative sources of nutraceutical uses. In the literature, hemp protein products (HPPs) have reported antioxidant and anti-inflammatory properties. This [...] Read more.
Hemp seeds have a wide variety of chemical compounds which present biological activity. Specifically, the focus on proteins and bioactive peptides are increasing as alternative sources of nutraceutical uses. In the literature, hemp protein products (HPPs) have reported antioxidant and anti-inflammatory properties. This study aimed to determine the inflammation-related modulatory effects of HPPs on lipopolysaccharide (LPS)-activated primary human monocytes. CD14+ cells were immunomagnetically isolated from buffy coats and the anti-inflammatory activity of hemp protein isolate (HPI) and hydrolysates (HPHs) was evaluated on LPS-stimulated human primary monocytes. The specific markers of inflammation, polarization, and chemoattraction were measured by RT-qPCR and ELISA assays. Our results showed that HPPs decreased the pro-inflammatory mediators (TNF-α, IL-1β, and IL-6) and increased the anti-inflammatory mediators (IL-10 and IL-4). In addition, M1 polarization marker gene expression (CCR7 and iNOS) was downregulated by HPPs and, M2 polarization marker gene expression (CD200R and MRC1) was upregulated. Finally, the mRNA expression of chemotaxis genes (CCR2 and CCL2) was downregulated by HPPs. In conclusion, this study suggests that HPPs may improve chronic inflammatory states and promote regenerative processes by reprogramming monocytes toward M2 polarization phenotype. Full article
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Open AccessArticle
Effect of Erufosine on Membrane Lipid Order in Breast Cancer Cell Models
Biomolecules 2020, 10(5), 802; https://doi.org/10.3390/biom10050802 - 22 May 2020
Viewed by 273
Abstract
Alkylphospholipids are a novel class of antineoplastic drugs showing remarkable therapeutic potential. Among them, erufosine (EPC3) is a promising drug for the treatment of several types of tumors. While EPC3 is supposed to exert its function by interacting with lipid membranes, the exact [...] Read more.
Alkylphospholipids are a novel class of antineoplastic drugs showing remarkable therapeutic potential. Among them, erufosine (EPC3) is a promising drug for the treatment of several types of tumors. While EPC3 is supposed to exert its function by interacting with lipid membranes, the exact molecular mechanisms involved are not known yet. In this work, we applied a combination of several fluorescence microscopy and analytical chemistry approaches (i.e., scanning fluorescence correlation spectroscopy, line-scan fluorescence correlation spectroscopy, generalized polarization imaging, as well as thin layer and gas chromatography) to quantify the effect of EPC3 in biophysical models of the plasma membrane, as well as in cancer cell lines. Our results indicate that EPC3 affects lipid–lipid interactions in cellular membranes by decreasing lipid packing and increasing membrane disorder and fluidity. As a consequence of these alterations in the lateral organization of lipid bilayers, the diffusive dynamics of membrane proteins are also significantly increased. Taken together, these findings suggest that the mechanism of action of EPC3 could be linked to its effects on fundamental biophysical properties of lipid membranes, as well as on lipid metabolism in cancer cells. Full article
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Open AccessArticle
Effects of Chronic Cannabidiol Treatment in the Rat Chronic Unpredictable Mild Stress Model of Depression
Biomolecules 2020, 10(5), 801; https://doi.org/10.3390/biom10050801 - 22 May 2020
Viewed by 303
Abstract
Several neuropharmacological actions of cannabidiol (CBD) due to the modulation of the endocannabinoid system as well as direct serotonergic and gamma-aminobutyric acidergic actions have recently been identified. The current study aimed to reveal the effect of a long-term CBD treatment in the chronic [...] Read more.
Several neuropharmacological actions of cannabidiol (CBD) due to the modulation of the endocannabinoid system as well as direct serotonergic and gamma-aminobutyric acidergic actions have recently been identified. The current study aimed to reveal the effect of a long-term CBD treatment in the chronic unpredictable mild stress (CUMS) model of depression. Adult male Wistar rats (n = 24) were exposed to various stressors on a daily basis in order to induce anhedonia and anxiety-like behaviors. CBD (10 mg/kg body weight) was administered by daily intraperitoneal injections for 28 days (n = 12). The effects of the treatment were assessed on body weight, sucrose preference, and exploratory and anxiety-related behavior in the open field (OF) and elevated plus maze (EPM) tests. Hair corticosterone was also assayed by liquid chromatography–mass spectrometry. At the end of the experiment, CBD-treated rats showed a higher rate of body weight gain (5.94% vs. 0.67%) and sucrose preference compared to controls. A significant increase in vertical exploration and a trend of increase in distance traveled in the OF test were observed in the CBD-treated group compared to the vehicle-treated group. The EPM test did not reveal any differences between the groups. Hair corticosterone levels increased in the CBD-treated group, while they decreased in controls compared to baseline (+36.01% vs. −45.91%). In conclusion, CBD exerted a prohedonic effect in rats subjected to CUMS, demonstrated by the increased sucrose preference after three weeks of treatment. The reversal of the effect of CUMS on hair corticosterone concentrations might also point toward an anxiolytic or antidepressant-like effect of CBD, but this needs further confirmation. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessArticle
Amaryllidaceae Alkaloids of Belladine-Type from Narcissus pseudonarcissus cv. Carlton as New Selective Inhibitors of Butyrylcholinesterase
Biomolecules 2020, 10(5), 800; https://doi.org/10.3390/biom10050800 - 22 May 2020
Viewed by 316
Abstract
Thirteen known (112 and 16) and three previously undescribed Amaryllidaceae alkaloids of belladine structural type, named carltonine A-C (1315), were isolated from bulbs of Narcissus pseudonarcissus cv. Carlton (Amaryllidaceae) by standard chromatographic methods. Compounds isolated [...] Read more.
Thirteen known (112 and 16) and three previously undescribed Amaryllidaceae alkaloids of belladine structural type, named carltonine A-C (1315), were isolated from bulbs of Narcissus pseudonarcissus cv. Carlton (Amaryllidaceae) by standard chromatographic methods. Compounds isolated in sufficient amounts, and not tested previously, were evaluated for their in vitro acetylcholinesterase (AChE; E.C. 3.1.1.7), butyrylcholinesterase (BuChE; E.C. 3.1.1.8) and prolyl oligopeptidase (POP; E.C. 3.4.21.26) inhibition activities. Significant human BuChE (hBUChE) inhibitory activity was demonstrated by newly described alkaloids carltonine A (13) and carltonine B (14) with IC50 values of 913 ± 20 nM and 31 ± 1 nM, respectively. Both compounds displayed a selective inhibition pattern for hBuChE with an outstanding selectivity profile over AChE inhibition, higher than 100. The in vitro data were further supported by in silico studies of the active alkaloids 13 and 14 in the active site of hBuChE. Full article
(This article belongs to the Special Issue Cholinesterase Research)
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Open AccessArticle
In Vitro Anti-Inflammatory, Anti-Oxidant, and Cytotoxic Activities of Four Curcuma Species and the Isolation of Compounds from Curcuma aromatica Rhizome
Biomolecules 2020, 10(5), 799; https://doi.org/10.3390/biom10050799 - 21 May 2020
Viewed by 283
Abstract
The genus Curcuma is part of the Zingiberaceae family, and many Curcuma species have been used as traditional medicine and cosmetics in Thailand. To find new cosmeceutical ingredients, the in vitro anti-inflammatory, anti-oxidant, and cytotoxic activities of four Curcuma species as well as [...] Read more.
The genus Curcuma is part of the Zingiberaceae family, and many Curcuma species have been used as traditional medicine and cosmetics in Thailand. To find new cosmeceutical ingredients, the in vitro anti-inflammatory, anti-oxidant, and cytotoxic activities of four Curcuma species as well as the isolation of compounds from the most active crude extract (C. aromatica) were investigated. The crude extract of C. aromatica showed 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity with an IC50 value of 102.3 μg/mL. The cytotoxicity effect of C. aeruginosa, C. comosa, C. aromatica, and C. longa extracts assessed with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay at 200 μg/mL were 12.1 ± 2.9, 14.4 ± 4.1, 28.6 ± 4.1, and 46.9 ± 8.6, respectively. C. aeruginosa and C. comosa presented apoptosis cells (57.7 ± 3.1% and 32.6 ± 2.2%, respectively) using the CytoTox-ONE™ assay. Different crude extracts or phytochemicals purified from C. aromatica were evaluated for their anti-inflammatory properties. The crude extract of C. aromatica showed the highest potential to inhibit NF-κB activity, followed by C. aeruginosa, C. comosa, and C. longa, respectively. Among the various purified phytochemicals curcumin, germacrone, curdione, zederone, and curcumenol significantly inhibited NF-κB activation in tumor necrosis factor (TNF) stimulated HaCaT keratinocytes. Of all compounds, curcumin was the most potent anti-inflammatory. Full article
(This article belongs to the Special Issue Phytochemical Omics in Medicinal Plants)
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Open AccessReview
Galectin-3: Roles in Neurodevelopment, Neuroinflammation, and Behavior
Biomolecules 2020, 10(5), 798; https://doi.org/10.3390/biom10050798 - 21 May 2020
Viewed by 312
Abstract
There is a plethora of evidence to suggest that Galectin-3 plays an important role in normal functions of mammalian cells, as well as in different pathogenic conditions. This review highlights recent data published by researchers, including our own team, on roles of Galectin-3 [...] Read more.
There is a plethora of evidence to suggest that Galectin-3 plays an important role in normal functions of mammalian cells, as well as in different pathogenic conditions. This review highlights recent data published by researchers, including our own team, on roles of Galectin-3 in the nervous system. Here, we discuss the roles of Galectin-3 in brain development, its roles in glial cells, as well as the interactions of glial cells with other neural and invading cells in pathological conditions. Galectin-3 plays an important role in the pathogenesis of neuroinflammatory and neurodegenerative disorders, such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. On the other hand, there is also evidence of the protective role of Galectin-3 due to its anti-apoptotic effect in target cells. Interestingly, genetic deletion of Galectin-3 affects behavioral patterns in maturing and adult mice. The results reviewed in this paper and recent development of highly specific inhibitors suggests that Galectin-3 may be an important therapeutic target in pathological conditions including the disorders of the central nervous system. Full article
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Open AccessArticle
Study of Synthesis Pathways of the Essential Polyunsaturated Fatty Acid 20:5n-3 in the Diatom Chaetoceros Muelleri Using 13C-Isotope Labeling
Biomolecules 2020, 10(5), 797; https://doi.org/10.3390/biom10050797 - 21 May 2020
Viewed by 291
Abstract
The present study sought to characterize the synthesis pathways producing the essential polyunsaturated fatty acid (PUFA) 20:5n-3 (EPA). For this, the incorporation of 13C was experimentally monitored into 10 fatty acids (FA) during the growth of the diatom Chaetoceros muelleri for 24 [...] Read more.
The present study sought to characterize the synthesis pathways producing the essential polyunsaturated fatty acid (PUFA) 20:5n-3 (EPA). For this, the incorporation of 13C was experimentally monitored into 10 fatty acids (FA) during the growth of the diatom Chaetoceros muelleri for 24 h. Chaetoceros muelleri preferentially and quickly incorporated 13C into C18 PUFAs such as 18:2n-6 and 18:3n-6 as well as 16:0 and 16:1n-7, which were thus highly 13C-enriched. During the experiment, 20:5n-3 and 16:3n-4 were among the least-enriched fatty acids. The calculation of the enrichment percentage ratio of a fatty acid B over its suspected precursor A allowed us to suggest that the diatom produced 20:5n-3 (EPA) by a combination between the n-3 (via 18:4n-3) and n-6 (via 18:3n-6 and 20:4n-6) synthesis pathways as well as the alternative ω-3 desaturase pathway (via 20:4n-6). In addition, as FA from polar lipids were generally more enriched in 13C than FA from neutral lipids, particularly for 18:1n-9, 18:2n-6 and 18:3n-6, the existence of acyl-editing mechanisms and connectivity between polar and neutral lipid fatty acid pools were also hypothesized. Because 16:3n-4 and 20:5n-3 presented the same concentration and enrichment dynamics, a structural and metabolic link was proposed between these two PUFAs in C. muelleri. Full article
(This article belongs to the Special Issue Lipids of Marine Algae)
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Open AccessFeature PaperArticle
Unstructured Biology of Proteins from Ubiquitin-Proteasome System: Roles in Cancer and Neurodegenerative Diseases
Biomolecules 2020, 10(5), 796; https://doi.org/10.3390/biom10050796 - 21 May 2020
Viewed by 520
Abstract
The 26S proteasome is a large (~2.5 MDa) protein complex consisting of at least 33 different subunits and many other components, which form the ubiquitin proteasomal system (UPS), an ATP-dependent protein degradation system in the cell. UPS serves as an essential component of [...] Read more.
The 26S proteasome is a large (~2.5 MDa) protein complex consisting of at least 33 different subunits and many other components, which form the ubiquitin proteasomal system (UPS), an ATP-dependent protein degradation system in the cell. UPS serves as an essential component of the cellular protein surveillance machinery, and its dysfunction leads to cancer, neurodegenerative and immunological disorders. Importantly, the functions and regulations of proteins are governed by the combination of ordered regions, intrinsically disordered protein regions (IDPRs) and molecular recognition features (MoRFs). The structure–function relationships of UPS components have not been identified completely; therefore, in this study, we have carried out the functional intrinsic disorder and MoRF analysis for potential neurodegenerative disease and anti-cancer targets of this pathway. Our report represents the presence of significant intrinsic disorder and disorder-based binding regions in several UPS proteins, such as extraproteasomal polyubiquitin receptors (UBQLN1 and UBQLN2), proteasome-associated polyubiquitin receptors (ADRM1 and PSMD4), deubiquitinating enzymes (DUBs) (ATXN3 and USP14), and ubiquitinating enzymes (E2 (UBE2R2) and E3 (STUB1) enzyme). We believe this study will have implications for the conformation-specific roles of different regions of these proteins. This will lead to a better understanding of the molecular basis of UPS-associated diseases. Full article
(This article belongs to the Special Issue The Amazing World of IDPs in Human Diseases)
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Open AccessArticle
Characterization of Chenopodin Isoforms from Quinoa Seeds and Assessment of Their Potential Anti-Inflammatory Activity in Caco-2 Cells
Biomolecules 2020, 10(5), 795; https://doi.org/10.3390/biom10050795 - 21 May 2020
Viewed by 245
Abstract
Several food-derived molecules, including proteins and peptides, can show bioactivities toward the promotion of well-being and disease prevention in humans. There is still a lack of information about the potential effects on immune and inflammatory responses in mammalian cells following the ingestion of [...] Read more.
Several food-derived molecules, including proteins and peptides, can show bioactivities toward the promotion of well-being and disease prevention in humans. There is still a lack of information about the potential effects on immune and inflammatory responses in mammalian cells following the ingestion of seed storage proteins. This study, for the first time, describes the potential immunomodulation capacity of chenopodin, the major protein component of quinoa seeds. After characterizing the molecular features of the purified protein, we were able to separate two different forms of chenopodin, indicated as LcC (Low charge Chenopodin, 30% of total chenopodin) and HcC (High charge Chenopodin, 70% of total chenopodin). The biological effects of LcC and HcC were investigated by measuring NF-κB activation and IL-8 expression studies in undifferentiated Caco-2 cells. Inflammation was elicited using IL-1β. The results indicate that LcC and HcC show potential anti-inflammatory activities in an intestinal cell model, and that the proteins can act differently, depending on their structural features. Furthermore, the molecular mechanisms of action and the structural/functional relationships of the protein at the basis of the observed bioactivity were investigated using in silico analyses and structural predictions. Full article
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Open AccessArticle
Crotoxin-Induced Mice Lung Impairment: Role of Nicotinic Acetylcholine Receptors and COX-Derived Prostanoids
Biomolecules 2020, 10(5), 794; https://doi.org/10.3390/biom10050794 - 20 May 2020
Viewed by 400
Abstract
Respiratory compromise in Crotalus durissus terrificus (C.d.t.) snakebite is an important pathological condition. Considering that crotoxin (CTX), a phospholipase A2 from C.d.t. venom, is the main component of the venom, the present work investigated the toxin effects on respiratory failure. Lung mechanics, [...] Read more.
Respiratory compromise in Crotalus durissus terrificus (C.d.t.) snakebite is an important pathological condition. Considering that crotoxin (CTX), a phospholipase A2 from C.d.t. venom, is the main component of the venom, the present work investigated the toxin effects on respiratory failure. Lung mechanics, morphology and soluble markers were evaluated from Swiss male mice, and mechanism determined using drugs/inhibitors of eicosanoids biosynthesis pathway and autonomic nervous system. Acute respiratory failure was observed, with an early phase (within 2 h) characterized by enhanced presence of eicosanoids, including prostaglandin E2, that accounted for the increased vascular permeability in the lung. The alterations of early phase were inhibited by indomethacin. The late phase (peaked 12 h) was marked by neutrophil infiltration, presence of pro-inflammatory cytokines/chemokines, and morphological alterations characterized by alveolar septal thickening and bronchoconstriction. In addition, lung mechanical function was impaired, with decreased lung compliance and inspiratory capacity. Hexamethonium, a nicotinic acetylcholine receptor antagonist, hampered late phase damages indicating that CTX-induced lung impairment could be associated with cholinergic transmission. The findings reported herein highlight the impact of CTX on respiratory compromise, and introduce the use of nicotinic blockers and prostanoids biosynthesis inhibitors as possible symptomatic therapy to Crotalus durissus terrificus snakebite. Full article
(This article belongs to the Special Issue Phospholipases: From Structure to Biological Function)
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Open AccessArticle
Effects of the Positive Allosteric Modulator of Metabotropic Glutamate Receptor 5, VU-29, on Maintenance Association between Environmental Cues and Rewarding Properties of Ethanol in Rats
Biomolecules 2020, 10(5), 793; https://doi.org/10.3390/biom10050793 - 20 May 2020
Viewed by 232
Abstract
Metabotropic glutamate subtype 5 (mGlu5) receptors are implicated in various forms of synaptic plasticity, including drugs of abuse. In drug-addicted individuals, associative memories can drive relapse to drug use. The present study investigated the potential of the mGlu5 receptor positive allosteric modulator (PAM), [...] Read more.
Metabotropic glutamate subtype 5 (mGlu5) receptors are implicated in various forms of synaptic plasticity, including drugs of abuse. In drug-addicted individuals, associative memories can drive relapse to drug use. The present study investigated the potential of the mGlu5 receptor positive allosteric modulator (PAM), VU-29 (30 mg/kg, i.p.), to inhibit the maintenance of a learned association between ethanol and environmental context by using conditioned place preference (CPP) in rats. The ethanol-CPP was established by the administration of ethanol (1.0 g/kg, i.p. ×10 days) using an unbiased procedure. Following ethanol conditioning, VU-29 was administered at various post-conditioning times (ethanol free state at the home cage) to ascertain if there was a temporal window during which VU-29 would be effective. Our experiments indicated that VU-29 did not affect the expression of ethanol-induced CPP when it was given over two post-conditioning days. However, the expression of ethanol-CPP was inhibited by 10-day home cage administration of VU-29, but not by first 2-day or last 2-day injection of VU-29 during the 10-day period. These findings reveal that VU-29 can inhibit the maintenance of ethanol-induced CPP, and that treatment duration contributes to this effect of VU-29. Furthermore, VU-29 effect was reversed by pretreatment with either MTEP (the mGlu5 receptor antagonist), or MK-801 (the N-methyl-D-aspartate-NMDA receptor antagonist). Thus, the inhibitory effect of VU-29 is dependent on the functional interaction between mGlu5 and NMDA receptors. Because a reduction in ethanol-associated cues can reduce relapse, mGlu5 receptor PAM would be useful for therapy of alcoholism. Future research is required to confirm the current findings. Full article
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Open AccessArticle
Antidepressant-Like Effect of Terpineol in an Inflammatory Model of Depression: Involvement of the Cannabinoid System and D2 Dopamine Receptor
Biomolecules 2020, 10(5), 792; https://doi.org/10.3390/biom10050792 - 20 May 2020
Viewed by 320
Abstract
Depression has a multifactorial etiology that arises from environmental, psychological, genetic, and biological factors. Environmental stress and genetic factors acting through immunological and endocrine responses generate structural and functional changes in the brain, inducing neurogenesis and neurotransmission dysfunction. Terpineol, monoterpenoid alcohol, has shown [...] Read more.
Depression has a multifactorial etiology that arises from environmental, psychological, genetic, and biological factors. Environmental stress and genetic factors acting through immunological and endocrine responses generate structural and functional changes in the brain, inducing neurogenesis and neurotransmission dysfunction. Terpineol, monoterpenoid alcohol, has shown immunomodulatory and neuroprotective effects, but there is no report about its antidepressant potential. Herein, we used a single lipopolysaccharide (LPS) injection to induce a depressive-like effect in the tail suspension test (TST) and the splash test (ST) for a preventive and therapeutic experimental schedule. Furthermore, we investigated the antidepressant-like mechanism of action of terpineol while using molecular and pharmacological approaches. Terpineol showed a coherent predicted binding mode mainly against CB1 and CB2 receptors and also against the D2 receptor during docking modeling analyses. The acute administration of terpineol produced the antidepressant-like effect, since it significantly reduced the immobility time in TST (100–200 mg/kg, p.o.) as compared to the control group. Moreover, terpineol showed an antidepressant-like effect in the preventive treatment that was blocked by a nonselective dopaminergic receptor antagonist (haloperidol), a selective dopamine D2 receptor antagonist (sulpiride), a selective CB1 cannabinoid receptor antagonist/inverse agonist (AM281), and a potent and selective CB2 cannabinoid receptor inverse agonist (AM630), but it was not blocked by a nonselective adenosine receptor antagonist (caffeine) or a β-adrenoceptor antagonist (propranolol). In summary, molecular docking suggests that CB1 and CB2 receptors are the most promising targets of terpineol action. Our data showed terpineol antidepressant-like modulation by CB1 and CB2 cannabinoid receptors and D2-dopaminergic receptors to further corroborate our molecular evidence. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessReview
The NRF2/KEAP1 Axis in the Regulation of Tumor Metabolism: Mechanisms and Therapeutic Perspectives
Biomolecules 2020, 10(5), 791; https://doi.org/10.3390/biom10050791 - 20 May 2020
Viewed by 293
Abstract
The NRF2/KEAP1 pathway is a fundamental signaling cascade that controls multiple cytoprotective responses through the induction of a complex transcriptional program that ultimately renders cancer cells resistant to oxidative, metabolic and therapeutic stress. Interestingly, accumulating evidence in recent years has indicated that metabolic [...] Read more.
The NRF2/KEAP1 pathway is a fundamental signaling cascade that controls multiple cytoprotective responses through the induction of a complex transcriptional program that ultimately renders cancer cells resistant to oxidative, metabolic and therapeutic stress. Interestingly, accumulating evidence in recent years has indicated that metabolic reprogramming is closely interrelated with the regulation of redox homeostasis, suggesting that the disruption of NRF2 signaling might represent a valid therapeutic strategy against a variety of solid and hematologic cancers. These aspects will be the focus of the present review. Full article
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Open AccessArticle
Biological Properties of a Novel Multifunctional Host Defense Peptide from the Skin Secretion of the Chaco Tree Frog, Boana raniceps
Biomolecules 2020, 10(5), 790; https://doi.org/10.3390/biom10050790 - 20 May 2020
Viewed by 274
Abstract
In recent years, the number of new antimicrobial drugs launched on the market has decreased considerably even though there has been an increase in the number of resistant microbial strains. Thus, antimicrobial resistance has become a serious public health problem. Amphibian skin secretions [...] Read more.
In recent years, the number of new antimicrobial drugs launched on the market has decreased considerably even though there has been an increase in the number of resistant microbial strains. Thus, antimicrobial resistance has become a serious public health problem. Amphibian skin secretions are a rich source of host defense peptides, which generally are cationic and hydrophobic molecules, with a broad-spectrum of activity. In this study, one novel multifunctional defense peptide was isolated from the skin secretion of the Chaco tree frog, Boana raniceps. Figainin 2 (1FLGAILKIGHALAKTVLPMVTNAFKPKQ28) is cationic and hydrophobic, adopts an α-helical structure in 50% (v/v) trifluoroethanol (TFE), and is thermally stable. This peptide exhibited activity against Gram-negative and Gram-positive pathogenic bacteria arboviruses, T. cruzi epimastigotes; however, it did not show activity against yeasts. Figainin 2 also showed antiproliferative activity on cancer cells, is moderately active on human erythrocytes, and activates the oxidative burst in human neutrophils. Full article
(This article belongs to the Section Natural and Bio-inspired Molecules)
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Open AccessArticle
MARK4 Inhibited by AChE Inhibitors, Donepezil and Rivastigmine Tartrate: Insights into Alzheimer’s Disease Therapy
Biomolecules 2020, 10(5), 789; https://doi.org/10.3390/biom10050789 - 20 May 2020
Viewed by 297
Abstract
Microtubule affinity-regulating kinase (MARK4) plays a key role in Alzheimer’s disease (AD) development as its overexpression is directly linked to increased tau phosphorylation. MARK4 is a potential drug target of AD and is thus its structural features are employed in the development of [...] Read more.
Microtubule affinity-regulating kinase (MARK4) plays a key role in Alzheimer’s disease (AD) development as its overexpression is directly linked to increased tau phosphorylation. MARK4 is a potential drug target of AD and is thus its structural features are employed in the development of new therapeutic molecules. Donepezil (DP) and rivastigmine tartrate (RT) are acetylcholinesterase (AChE) inhibitors and are used to treat symptomatic patients of mild to moderate AD. In keeping with the therapeutic implications of DP and RT in AD, we performed binding studies of these drugs with the MARK4. Both DP and RT bound to MARK4 with a binding constant (K) of 107 M−1. The temperature dependency of binding parameters revealed MARK−DP complex to be guided by static mode while MARK−RT complex to be guided by both static and dynamic quenching. Both drugs inhibited MARK4 with IC50 values of 5.3 μM (DP) and 6.74 μM (RT). The evaluation of associated enthalpy change (ΔH) and entropy change (ΔS) implied the complex formation to be driven by hydrogen bonding making it seemingly strong and specific. Isothermal titration calorimetry further advocated a spontaneous binding. In vitro observations were further complemented by the calculation of binding free energy by molecular docking and interactions with the functionally-important residues of the active site pocket of MARK4. This study signifies the implications of AChE inhibitors, RT, and DP in Alzheimer’s therapy targeting MARK4. Full article
(This article belongs to the Section Natural and Bio-inspired Molecules)
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Open AccessArticle
Different Impacts of MucR Binding to the babR and virB Promoters on Gene Expression in Brucella abortus 2308
Biomolecules 2020, 10(5), 788; https://doi.org/10.3390/biom10050788 - 19 May 2020
Viewed by 293
Abstract
The protein MucR from Brucella abortus has been described as a transcriptional regulator of many virulence genes. It is a member of the Ros/MucR family comprising proteins that control the expression of genes important for the successful interaction of α-proteobacteria with their eukaryotic [...] Read more.
The protein MucR from Brucella abortus has been described as a transcriptional regulator of many virulence genes. It is a member of the Ros/MucR family comprising proteins that control the expression of genes important for the successful interaction of α-proteobacteria with their eukaryotic hosts. Despite clear evidence of the role of MucR in repressing virulence genes, no study has been carried out so far demonstrating the direct interaction of this protein with the promoter of its target gene babR encoding a LuxR-like regulator repressing virB genes. In this study, we show for the first time the ability of MucR to bind the promoter of babR in electrophoretic mobility shift assays demonstrating a direct role of MucR in repressing this gene. Furthermore, we demonstrate that MucR can bind the virB gene promoter. Analyses by RT-qPCR showed no significant differences in the expression level of virB genes in Brucella abortus CC092 lacking MucR compared to the wild-type Brucella abortus strain, indicating that MucR binding to the virB promoter has little impact on virB gene expression in B. abortus 2308. The MucR modality to bind the two promoters analyzed supports our previous hypothesis that this is a histone-like protein never found before in Brucella. Full article
(This article belongs to the Section Molecular Biology)
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Open AccessArticle
A Comparison between Several Response Surface Methodology Designs and a Neural Network Model to Optimise the Oxidation Conditions of a Lignocellulosic Blend
Biomolecules 2020, 10(5), 787; https://doi.org/10.3390/biom10050787 - 19 May 2020
Viewed by 280
Abstract
In this paper, response surface methodology (RSM) designs and an artificial neural network (ANN) are used to obtain the optimal conditions for the oxy-combustion of a corn–rape blend. The ignition temperature (Te) and burnout index (Df) were [...] Read more.
In this paper, response surface methodology (RSM) designs and an artificial neural network (ANN) are used to obtain the optimal conditions for the oxy-combustion of a corn–rape blend. The ignition temperature (Te) and burnout index (Df) were selected as the responses to be optimised, while the CO2/O2 molar ratio, the total flow, and the proportion of rape in the blend were chosen as the influencing factors. For the RSM designs, complete, Box–Behnken, and central composite designs were performed to assess the experimental results. By applying the RSM, it was found that the principal effects of the three factors were statistically significant to compute both responses. Only the interactions of the factors on Df were successfully described by the Box–Behnken model, while the complete design model was adequate to describe such interactions on both responses. The central composite design was found to be inadequate to describe the factor interactions. Nevertheless, the three methods predicted the optimal conditions properly, due to the cancellation of net positive and negative errors in the mathematical adjustment. The ANN presented the highest regression coefficient of all methods tested and needed only 20 experiments to reach the best predictions, compared with the 32 experiments needed by the best RSM method. Hence, the ANN was found to be the most efficient model, in terms of good prediction ability and a low resource requirement. Finally, the optimum point was found to be a CO2/O2 molar ratio of 3.3, a total flow of 108 mL/min, and 61% of rape in the biomass blend. Full article
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Open AccessArticle
Oral Administration of Liquiritigenin Confers Protection from Atopic Dermatitis through the Inhibition of T Cell Activation
Biomolecules 2020, 10(5), 786; https://doi.org/10.3390/biom10050786 - 19 May 2020
Viewed by 228
Abstract
While liquiritigenin, isolated from Spatholobus suberectus Dunn, is known to possess anti-inflammatory activities, it still remains to be known whether liquiritigenin has a suppressive effect on T cell activation and T cell-mediated disease. Here, we used Jurkat T cells to explore an [...] Read more.
While liquiritigenin, isolated from Spatholobus suberectus Dunn, is known to possess anti-inflammatory activities, it still remains to be known whether liquiritigenin has a suppressive effect on T cell activation and T cell-mediated disease. Here, we used Jurkat T cells to explore an underlying mechanism of pre-treatment with liquiritigenin in activated T cell in vitro and used atopic dermatitis (AD) in vivo to confirm it. We found liquiritigenin blocks IL-2 and CD69 expression from activated T cells by PMA/A23187 or anti-CD3/CD28 antibodies. The expressions of surface molecules, including CD40L and CD25, were also reduced in activated T cells pre-treated with liquiritigenin. Western blot analysis indicated repressive effects by liquiritigenin are involved in NFκB and MAPK pathways. To assess the effects of liquiritigenin in vivo, an AD model was applied as T cell-mediated disease. Oral administration of liquiritigenin attenuates AD manifestations, including ear thickness, IgE level, and thicknesses of dermis and epidermis. Systemic protections by liquiritigenin were observed to be declined in size and weight of draining lymph nodes (dLNs) and expressions of effector cytokines from CD4+ T cells in dLNs. These results suggest liquiritigenin has an anti-atopic effect via control of T cell activation and exhibits therapeutic potential for T cell-mediated disorders. Full article
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Open AccessArticle
Green Synthesis of MnO Nanoparticles Using Abutilon indicum Leaf Extract for Biological, Photocatalytic, and Adsorption Activities
Biomolecules 2020, 10(5), 785; https://doi.org/10.3390/biom10050785 - 19 May 2020
Viewed by 270
Abstract
We report the synthesis of MnO nanoparticles (AI-MnO NAPs) using biological molecules of Abutilon indicum leaf extract. Further, they were evaluated for antibacterial and cytotoxicity activity against different pathogenic microbes (Escherichia coli, Bordetella bronchiseptica, Staphylococcus aureus, and Bacillus subtilis [...] Read more.
We report the synthesis of MnO nanoparticles (AI-MnO NAPs) using biological molecules of Abutilon indicum leaf extract. Further, they were evaluated for antibacterial and cytotoxicity activity against different pathogenic microbes (Escherichia coli, Bordetella bronchiseptica, Staphylococcus aureus, and Bacillus subtilis) and HeLa cancerous cells. Synthesized NAPs were also investigated for photocatalytic dye degradation potential against methylene blue (MB), and adsorption activity against Cr(VI) was also determined. Results from Scanning electron microscope (SEM), X-ray powder diffraction (XRD), Energy-dispersive X-ray (EDX), and Fourier-transform infrared spectroscopy (FTIR) confirmed the successful synthesis of NAPs with spherical morphology and crystalline nature. Biological activity results demonstrated that synthesized AI-MnO NAPs exhibited significant antibacterial and cytotoxicity propensities against pathogenic microbes and cancerous cells, respectively, compared with plant extract. Moreover, synthesized AI-MnO NAPs demonstrated the comparable biological activities results to standard drugs. These excellent biological activities results are attributed to the existence of the plant’s biological molecules on their surfaces and small particle size (synergetic effect). Synthesized NAPs displayed better MB-photocatalyzing properties under sunlight than an ultraviolet lamp. The Cr(VI) adsorption result showed that synthesized NAPs efficiently adsorbed more Cr(VI) at higher acidic pH than at basic pH. Hence, the current findings suggest that Abutilon indicum is a valuable source for tailoring the potential of NAPs toward various enhanced biological, photocatalytic, and adsorption activities. Consequently, the plant’s biological molecule-mediated synthesized AI-MnO NAPs could be excellent contenders for future therapeutic applications. Full article
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Open AccessArticle
Exposure of Intestinal Epithelial Cells to 2′-Fucosyllactose and CpG Enhances Galectin Release and Instructs Dendritic Cells to Drive Th1 and Regulatory-Type Immune Development
Biomolecules 2020, 10(5), 784; https://doi.org/10.3390/biom10050784 - 19 May 2020
Viewed by 303
Abstract
Intestinal epithelial cells (IEC) release immunomodulatory galectins upon exposure to CpG DNA (mimicking bacterial triggers) and short-chain galacto- and long-chain fructo-oligosaccharides (GF). This study aims to investigate the immunomodulatory properties of 2′-fucosyllactose (2′-FL), a non-digestible oligosaccharide (NDO) abundantly present in human milk, using [...] Read more.
Intestinal epithelial cells (IEC) release immunomodulatory galectins upon exposure to CpG DNA (mimicking bacterial triggers) and short-chain galacto- and long-chain fructo-oligosaccharides (GF). This study aims to investigate the immunomodulatory properties of 2′-fucosyllactose (2′-FL), a non-digestible oligosaccharide (NDO) abundantly present in human milk, using a co-culture model developed to study the crosstalk between IEC and innate and adaptive immune cells. IECs, co-cultured with αCD3/CD28-activated peripheral blood mononuclear cells (PBMC), were apically exposed to NDOs and CpG, washed and co-cultured with immature monocyte-derived dendritic cells (moDC). Subsequently, moDC were co-cultured with naïve CD4+ T-cells. In the presence of CpG, both 2′-FL or GF-exposed IEC enhanced Th1-type IFNγ and regulatory IL-10 secretion of PBMCs, compared to CpG alone, while Th2-type IL-13 was reduced. Both NDOs increased IEC-derived galectin-3, -4, -9 and TGF-β1 of CpG-exposed IEC. Only galectin-9 correlated with all modified immune parameters and TGF-β1 secretion. MoDCs exposed to 2′-FL and CpG-conditioned IEC instructed IFNγ and IL-10 secretion by CD4+ T-cells, suggesting the development of a regulatory Th1 response. These results reveal that 2′-FL and GF could contribute to the mucosal immune development by supporting the effect of microbial CpG DNA associated with the modulation of epithelial galectin and TGF-β1 secretion. Full article
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Open AccessReview
snoRNPs: Functions in Ribosome Biogenesis
Biomolecules 2020, 10(5), 783; https://doi.org/10.3390/biom10050783 - 18 May 2020
Viewed by 521
Abstract
Ribosomes are perhaps the most critical macromolecular machine as they are tasked with carrying out protein synthesis in cells. They are incredibly complex structures composed of protein components and heavily chemically modified RNAs. The task of assembling mature ribosomes from their component parts [...] Read more.
Ribosomes are perhaps the most critical macromolecular machine as they are tasked with carrying out protein synthesis in cells. They are incredibly complex structures composed of protein components and heavily chemically modified RNAs. The task of assembling mature ribosomes from their component parts consumes a massive amount of energy and requires greater than 200 assembly factors. Among the most critical of these are small nucleolar ribonucleoproteins (snoRNPs). These are small RNAs complexed with diverse sets of proteins. As suggested by their name, they localize to the nucleolus, the site of ribosome biogenesis. There, they facilitate multiple roles in ribosomes biogenesis, such as pseudouridylation and 2′-O-methylation of ribosomal (r)RNA, guiding pre-rRNA processing, and acting as molecular chaperones. Here, we reviewed their activity in promoting the assembly of ribosomes in eukaryotes with regards to chemical modification and pre-rRNA processing. Full article
(This article belongs to the Special Issue Ribonucleoprotein Particles (RNPs): From Structure to Function)
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Open AccessArticle
Lifestyle Characteristics and Gene Expression Analysis of Colletotrichum camelliae Isolated from Tea Plant [Camellia sinensis (L.) O. Kuntze] Based on Transcriptome
Biomolecules 2020, 10(5), 782; https://doi.org/10.3390/biom10050782 - 18 May 2020
Viewed by 297
Abstract
Colletotrichum camelliae is one of the most serious pathogens causing anthracnose in tea plants, but the interactive relationship between C. camelliae and tea plants has not been fully elucidated. This study investigated the gene expression changes in five different growth stages of C. [...] Read more.
Colletotrichum camelliae is one of the most serious pathogens causing anthracnose in tea plants, but the interactive relationship between C. camelliae and tea plants has not been fully elucidated. This study investigated the gene expression changes in five different growth stages of C. camelliae based on transcriptome analysis to explain the lifestyle characteristics during the infection. On the basis of gene ontology (GO) enrichment analyses of differentially expressed genes (DEGs) in comparisons of germ tube (GT)/conidium (Con), appressoria (App)/Con, and cellophane infectious hyphae (CIH)/Con groups, the cellular process in the biological process category and intracellular, intracellular part, cell, and cell part in the cellular component category were significantly enriched. Hydrolase activity, catalytic activity, and molecular_function in the molecular function category were particularly enriched in the infection leaves (IL)/Con group. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the DEGs were enriched in the genetic information processing pathway (ribosome) at the GT stage and the metabolism pathway (metabolic pathways and biosynthesis of secondary metabolism) in the rest of the stages. Interestingly, the genes associated with melanin biosynthesis and carbohydrate-active enzymes (CAZys), which are vital for penetration and cell wall degradation, were significantly upregulated at the App, CIH and IL stages. Subcellular localization results further showed that the selected non-annotated secreted proteins based on transcriptome data were majorly located in the cytoplasm and nucleus, predicted as new candidate effectors. The results of this study may establish a foundation and provide innovative ideas for subsequent research on C. camelliae. Full article
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