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Biomolecules, Volume 9, Issue 12 (December 2019)

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Open AccessArticle
RSM–GA Based Optimization of Bacterial PHA Production and In Silico Modulation of Citrate Synthase for Enhancing PHA Production
Biomolecules 2019, 9(12), 872; https://doi.org/10.3390/biom9120872 (registering DOI) - 12 Dec 2019
Abstract
The inexhaustible nature and biodegradability of bioplastics like polyhydroxyalkanoates (PHAs) make them suitable assets to replace synthetic plastics. The eventual fate of these eco-friendly and non-toxic bioplastics relies upon the endeavors towards satisfying cost and, in addition, execution necessity. In this study, we [...] Read more.
The inexhaustible nature and biodegradability of bioplastics like polyhydroxyalkanoates (PHAs) make them suitable assets to replace synthetic plastics. The eventual fate of these eco-friendly and non-toxic bioplastics relies upon the endeavors towards satisfying cost and, in addition, execution necessity. In this study, we utilized and statistically optimized different food (kitchen-/agro-) waste as a sole carbon/nitrogen source for the production of PHA at a reduced cost, indicating a proficient waste administration procedure. Seven different types of kitchen-/agro-waste were used as unique carbon source and four different types of nitrogen source were used to study their impact on PHA production by Bacillus subtilis MTCC 144. Among four different studied production media, mineral salt medium (MSM) (biomass: 37.7 g/L; cell dry weight: 1.8 g/L; and PHA: 1.54 g/L) was found most suitable for PHA production. Further, carbon and nitrogen components of MSM were optimized using one-factor-at-a-time experiments, and found that watermelon rind (PHA = 12.97 g/L) and pulse peel (PHA = 13.5 g/L) were the most suitable carbon and nitrogen sources, respectively, in terms of PHA (78.60%) recovery. The concentrations of these factors (sources) were statistically optimized using response surface methodology coupled with the genetic algorithm approach. Additionally, in order to enhance microbial PHA production, the interaction of citrate synthase, a key enzyme in the TCA cycle, with different known inhibitors was studied using in silico molecular docking approach. The inhibition of citrate synthase induces the blockage of the tricarboxylic cycle (TCA), thereby increasing the concentration of acetyl-CoA that helps in enhanced PHA production. Molecular docking of citrate synthase with different inhibitors of PubChem database revealed that hesperidin (PubChem compound CID ID 10621), generally present in citrus fruits, is the most efficient inhibitor of the TCA cycle with the binding score of –11.4 and warrants experimental validation. Overall, this study provides an efficient food waste management approach by reducing the production cost and enhancing the production of PHA, thereby lessening our reliance on petroleum-based plastics. Full article
(This article belongs to the Special Issue Biology, Biotechnology and Bioprospecting of Microbial Biomolecules)
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Open AccessArticle
Lagerstroemia speciosa (L.) Pers Leaf Extract Attenuates Lung Tumorigenesis via Alleviating Oxidative Stress, Inflammation and Apoptosis
Biomolecules 2019, 9(12), 871; https://doi.org/10.3390/biom9120871 (registering DOI) - 12 Dec 2019
Abstract
One of the major etiological factors that account for lung cancer is tobacco use. Benzo(a)pyrene [B(a)P], one of the main constituents of tobacco smoke, has a key role in lung carcinogenesis. The present study was conducted to investigate the cytotoxicity of an [...] Read more.
One of the major etiological factors that account for lung cancer is tobacco use. Benzo(a)pyrene [B(a)P], one of the main constituents of tobacco smoke, has a key role in lung carcinogenesis. The present study was conducted to investigate the cytotoxicity of an aqueous ethanolic extract of Lagerstroemia speciosa (L.) Pers leaves (LLE) on human lung adenocarcinoma cells (A549), as well as its in vivo antitumor effect on a lung tumorigenesis mice model. Our results revealed that LLE possesses cytotoxic activity against the A549 cell line. Mice orally administered B(a)P (50 mg/kg body weight) showed an increase in relative lung weight with subsequent decrease in final body weight. Serum levels of tumor marker enzymes AHH, ADA and LDH and the inflammatory mediator NF-κB increased, while total antioxidant capacity (TAC) decreased. In addition, we observed the increased activity of metalloproteinases (MMP-2 and MMP-12) and levels of the tumor angiogenesis marker VEFG and the lipid peroxidation marker MDA, as well as decreased levels of the non-enzymatic antioxidant GSH and enzymatic antioxidants CAT and GSH-Px in lung tissues. Moreover, B(a)P administration up-regulated the expression of the COX-2 gene, pro-inflammatory cytokines TNF-α and IL-6, and an anti-apoptotic gene Bcl-2, and at the same time down-regulated expression of pro-apoptotic genes BAX and caspase-3 and the p53 gene. Pre- and post-treatment with LLE (250 mg/kg body weight) attenuated all these abnormalities. Histopathological observations verified the protective effect of LLE. Overall, the present data positively confirm the potent antitumor effect of L. speciosa leaves against lung tumorigenesis. Full article
(This article belongs to the Special Issue Antitumor Agents from Natural Sources)
Open AccessArticle
Biological Evaluation, Molecular Docking, and SAR Studies of Novel 2-(2,4-Dihydroxyphenyl)-1H- Benzimidazole Analogues
Biomolecules 2019, 9(12), 870; https://doi.org/10.3390/biom9120870 (registering DOI) - 12 Dec 2019
Abstract
In the present study, new 4-(1H-benzimidazol-2-yl)-benzene-1,3-diols, modified in both rings, have been synthesized and their efficacies as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors have been determined. The modified Ellman’s spectrophotometric method was applied for the biological evaluation. The compounds showed strong [...] Read more.
In the present study, new 4-(1H-benzimidazol-2-yl)-benzene-1,3-diols, modified in both rings, have been synthesized and their efficacies as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors have been determined. The modified Ellman’s spectrophotometric method was applied for the biological evaluation. The compounds showed strong (IC₅₀ 80–90 nM) AChE and moderate (IC₅₀ 5–0.2 µM) BuChE inhibition in vitro. Some compounds were effective toward AChE/BuChE, exhibiting high selectivity ratios versus BuChE, while the other compounds were active against both enzymes. The structure–activity relationships were discussed. The compounds inhibited also in vitro self-induced Aβ(1–42) aggregation and exhibited antioxidant properties. The docking simulations showed that the benzimidazoles under consideration interact mainly with the catalytic site of AChE and mimic the binding mode of tacrine. Full article
(This article belongs to the Special Issue Advances in Cholinesterases)
Open AccessArticle
The Integrity of α-β-α Sandwich Conformation Is Essential for a Novel Adjuvant TFPR1 to Maintain Its Adjuvanticity
Biomolecules 2019, 9(12), 869; https://doi.org/10.3390/biom9120869 (registering DOI) - 12 Dec 2019
Abstract
TFPR1 is a novel peptide vaccine adjuvant we recently discovered. To define the structural basis and optimize its application as an adjuvant, we designed three different truncated fragments that have removed dominant B epitopes on TFPR1, and evaluated their capacity to activate bone [...] Read more.
TFPR1 is a novel peptide vaccine adjuvant we recently discovered. To define the structural basis and optimize its application as an adjuvant, we designed three different truncated fragments that have removed dominant B epitopes on TFPR1, and evaluated their capacity to activate bone marrow-derived dendritic cells and their adjuvanticity. Results demonstrated that the integrity of an α-β-α sandwich conformation is essential for TFPR1 to maintain its immunologic activity and adjuvanticity. We obtained a functional truncated fragment TFPR-ta ranging from 40–168 aa of triflin that has similar adjuvanticity as TFPR1 but with 2-log fold lower immunogenicity. These results demonstrated a novel approach to evaluate and improve the activity of protein-based vaccine adjuvant. Full article
Open AccessArticle
Generation of Lamprey Monoclonal Antibodies (Lampribodies) Using the Phage Display System
Biomolecules 2019, 9(12), 868; https://doi.org/10.3390/biom9120868 (registering DOI) - 12 Dec 2019
Abstract
The variable lymphocyte receptors (VLRs) consist of leucine rich repeats (LRRs) and comprise the humoral antibodies produced by lampreys and hagfishes. The diversity of the molecules is generated by stepwise genomic rearrangements of LRR cassettes dispersed throughout the VLRB locus. Previously, target-specific monovalent [...] Read more.
The variable lymphocyte receptors (VLRs) consist of leucine rich repeats (LRRs) and comprise the humoral antibodies produced by lampreys and hagfishes. The diversity of the molecules is generated by stepwise genomic rearrangements of LRR cassettes dispersed throughout the VLRB locus. Previously, target-specific monovalent VLRB antibodies were isolated from sea lamprey larvae after immunization with model antigens. Further, the cloned VLR cDNAs from activated lamprey leukocytes were transfected into human cell lines or yeast to select best binders. Here, we expand on the overall utility of the VLRB technology by introducing it into a filamentous phage display system. We first tested the efficacy of isolating phage into which known VLRB molecules were cloned after a series of dilutions. These experiments showed that targeted VLRB clones could easily be recovered even after extensive dilutions (1 to 109). We further utilized the system to isolate target-specific “lampribodies” from phage display libraries from immunized animals and observed an amplification of binders with relative high affinities by competitive binding. The lampribodies can be individually purified and ostensibly utilized for applications for which conventional monoclonal antibodies are employed. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
Open AccessArticle
The Interplay between Retinal Pathways of Cholesterol Output and Its Effects on Mouse Retina
Biomolecules 2019, 9(12), 867; https://doi.org/10.3390/biom9120867 (registering DOI) - 12 Dec 2019
Abstract
In mammalian retina, cholesterol excess is mainly metabolized to oxysterols by cytochromes P450 27A1 (CYP27A1) and 46A1 (CYP46A1) or removed on lipoprotein particles containing apolipoprotein E (APOE). In contrast, esterification by sterol-O-acyltransferase 1 (SOAT) plays only a minor role in this process. Accordingly, [...] Read more.
In mammalian retina, cholesterol excess is mainly metabolized to oxysterols by cytochromes P450 27A1 (CYP27A1) and 46A1 (CYP46A1) or removed on lipoprotein particles containing apolipoprotein E (APOE). In contrast, esterification by sterol-O-acyltransferase 1 (SOAT) plays only a minor role in this process. Accordingly, retinal cholesterol levels are unchanged in Soat1−/− mice but are increased in Cyp27a1−/−Cyp46a1−/− and Apoe−/− mice. Herein, we characterized Cyp27a1−/−Cyp46a1−/−Soat1−/− and Cyp27a1−/−Cyp46a1−/−Apoe−/− mice. In the former, retinal cholesterol levels, anatomical gross structure, and vasculature were normal, yet the electroretinographic responses were impaired. Conversely, in Cyp27a1−/−Cyp46a1−/−Apoe−/− mice, retinal cholesterol levels were increased while anatomical structure and vasculature were unaffected with only male mice showing a decrease in electroretinographic responses. Sterol profiling, qRT-PCR, proteomics, and transmission electron microscopy mapped potential compensatory mechanisms in the Cyp27a1−/−Cyp46a1−/−Soat1−/− and Cyp27a1−/−Cyp46a1−/−Apoe−/− retina. These included decreased cholesterol biosynthesis along with enhanced formation of intra- and extracellular vesicles, possibly a reserve mechanism for lowering retinal cholesterol. In addition, there was altered abundance of proteins in Cyp27a1−/−Cyp46a1−/−Soat1−/− mice that can affect photoreceptor function, survival, and retinal energy homeostasis (glucose and fatty acid metabolism). Therefore, the levels of retinal cholesterol do not seem to predict retinal abnormalities, and it is rather the network of compensatory mechanisms that appears to determine retinal phenotype. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle
Model of Early Stage Intermediate in Respect to Its Final Structure
Biomolecules 2019, 9(12), 866; https://doi.org/10.3390/biom9120866 (registering DOI) - 12 Dec 2019
Abstract
The model, describing a method of determining the structure of an early intermediate in the process of protein folding to analyze nonredundant PDB protein bases, allows determining the relationship between the sequence of tetrapeptides and their structural forms expressed by structural codes. The [...] Read more.
The model, describing a method of determining the structure of an early intermediate in the process of protein folding to analyze nonredundant PDB protein bases, allows determining the relationship between the sequence of tetrapeptides and their structural forms expressed by structural codes. The contingency table expressing such a relationship can be used to predict the structure of polypeptides by proposing a structural form with a precision limited to the structural code. However, by analyzing structural forms in native forms of proteins based on the fuzzy oil drop model, one can also determine the status of polypeptide chain fragments with respect to the assumptions of this model. Whether the probability distributions for both compliant and noncompliant forms were similar or whether the tetrapeptide sequences showed some differences at a level of a set of structural codes was investigated. The analysis presented here indicated that some sequences in both forms revealed differences in probability distributions expressed as a negative statistically significant correlation coefficient. This meant that the identified sections (tetrapeptides) took different forms against the fuzzy oil drop model. It may suggest that the information of the final status with respect to hydrophobic core formation is already carried by the structure of the early-stage intermediate. Full article
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Open AccessArticle
Long-Lasting Effects of GSPE on Ileal GLP-1R Gene Expression Are Associated with a Hypomethylation of the GLP-1R Promoter in Female Wistar Rats
Biomolecules 2019, 9(12), 865; https://doi.org/10.3390/biom9120865 (registering DOI) - 12 Dec 2019
Abstract
Flavonoids have been shown to modulate GLP-1 in obesity. GLP-1 induces some of its effects through the intestinal GLP-1 receptor (GLP-1R), though no data exist on how flavonoids affect this receptor. Here, we examine how a dose of grape seed proanthocyanidin [...] Read more.
Flavonoids have been shown to modulate GLP-1 in obesity. GLP-1 induces some of its effects through the intestinal GLP-1 receptor (GLP-1R), though no data exist on how flavonoids affect this receptor. Here, we examine how a dose of grape seed proanthocyanidin extract (GSPE) with anti-obesity activity affects intestinal GLP-1R and analyze whether epigenetics play a role in the long-lasting effects of GSPE. We found that 10-day GSPE administration prior to the cafeteria diet upregulated GLP-1R mRNA in the ileum 17 weeks after the GSPE treatment. This was associated with a hypomethylation of the GLP-1R promoter near the region where the SP1 transcription factor binds. In the colon, the cafeteria diet upregulated GLP-1R without showing any GSPE effect. In conclusion, we have identified long-lasting GSPE effects on GLP-1R gene expression in the ileum that are partly mediated by hypomethylation at the gene promoter and may affect the SP1 binding factor. Full article
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Open AccessArticle
Critical Factors in Human Antizymes that Determine the Differential Binding, Inhibition, and Degradation of Human Ornithine Decarboxylase
Biomolecules 2019, 9(12), 864; https://doi.org/10.3390/biom9120864 (registering DOI) - 12 Dec 2019
Abstract
Antizyme (AZ) is a protein that negatively regulates ornithine decarboxylase (ODC). AZ achieves this inhibition by binding to ODC to produce AZ-ODC heterodimers, abolishing enzyme activity and targeting ODC for degradation by the 26S proteasome. In this study, we focused on the biomolecular [...] Read more.
Antizyme (AZ) is a protein that negatively regulates ornithine decarboxylase (ODC). AZ achieves this inhibition by binding to ODC to produce AZ-ODC heterodimers, abolishing enzyme activity and targeting ODC for degradation by the 26S proteasome. In this study, we focused on the biomolecular interactions between the C-terminal domain of AZ (AZ95–228) and ODC to identify the functional elements of AZ that are essential for binding, inhibiting and degrading ODC, and we also identified the crucial factors governing the differential binding and inhibition ability of AZ isoforms toward ODC. Based on the ODC inhibition and AZ-ODC binding studies, we demonstrated that amino acid residues reside within the α1 helix, β5 and β6 strands, and connecting loop between β6 and α2 (residues 142–178), which is the posterior part of AZ95–228, play crucial roles in ODC binding and inhibition. We also identified the essential elements determining the ODC-degradative activity of AZ; amino acid residues within the anterior part of AZ95–228 (residues 120–145) play crucial roles in AZ-mediated ODC degradation. Finally, we identified the crucial factors that govern the differential binding and inhibition of AZ isoforms toward ODC. Mutagenesis studies of AZ1 and AZ3 and their binding and inhibition revealed that the divergence of amino acid residues 124, 150, 166, 171, and 179 results in the differential abilities of AZ1 and AZ3 in the binding and inhibition of ODC. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle
Lemon-Fruit-Based Green Synthesis of Zinc Oxide Nanoparticles and Titanium Dioxide Nanoparticles against Soft Rot Bacterial Pathogen Dickeya dadantii
Biomolecules 2019, 9(12), 863; https://doi.org/10.3390/biom9120863 - 11 Dec 2019
Viewed by 158
Abstract
Edible plant fruits are safe raw materials free of toxicants and rich in biomolecules for reducing metal ions and stabilizing nanoparticles. Zinc oxide nanoparticles (ZnONPs) and titanium dioxide nanoparticles (TiO2NPs) are the most produced consumer nanomaterials and have known antibacterial activities [...] Read more.
Edible plant fruits are safe raw materials free of toxicants and rich in biomolecules for reducing metal ions and stabilizing nanoparticles. Zinc oxide nanoparticles (ZnONPs) and titanium dioxide nanoparticles (TiO2NPs) are the most produced consumer nanomaterials and have known antibacterial activities but have rarely been used against phytopathogenic bacteria. Here, we synthesized ZnONPs and TiO2NPs simply by mixing ZnO or TiO2 solution with a lemon fruit extract at room temperature and showed their antibacterial activities against Dickeya dadantii, which causes sweet potato stem and root rot disease occurring in major sweet potato planting areas in China. Ultraviolet–visible spectrometry and energy dispersive spectroscopy determined their physiochemical characteristics. Transmission electron microscopy, scanning electron microscopy, and X-ray diffraction spectroscopy revealed the nanoscale size and polymorphic crystalline structures of the ZnONPs and TiO2NPs. Fourier-transform infrared spectroscopy revealed their surface stabilization groups from the lemon fruit extract. In contrast to ZnO and TiO2, which had no antibacterial activity against D. dadantii, ZnONPs and TiO2NPs showed inhibitions on D. dadantii growth, swimming motility, biofilm formation, and maceration of sweet potato tuber slices. ZnONPs and TiO2NPs showed similar extents of antibacterial activities, which increased with the increase of nanoparticle concentrations, and inhibited about 60% of D. dadantii activities at the concentration of 50 µg∙mL-1. The green synthetic ZnONPs and TiO2NPs can be used to control the sweet potato soft rot disease by control of pathogen contamination of seed tubers. Full article
Open AccessArticle
Identification of Homeobox Genes Associated with Lignification and Their Expression Patterns in Bamboo Shoots
Biomolecules 2019, 9(12), 862; https://doi.org/10.3390/biom9120862 - 11 Dec 2019
Viewed by 115
Abstract
: Homeobox (HB) genes play critical roles in regulating various aspects of plant growth and development. However, little is known about HB genes in bamboo. In this study, a total of 115 HB genes (PeHB001PeHB115) were identified from moso [...] Read more.
: Homeobox (HB) genes play critical roles in regulating various aspects of plant growth and development. However, little is known about HB genes in bamboo. In this study, a total of 115 HB genes (PeHB001PeHB115) were identified from moso bamboo (Phyllostachys edulis) and grouped into 13 distinct classes (BEL, DDT, HD-ZIP I‒IV, KNOX, NDX, PHD, PINTOX, PLINC, SAWADEE, and WOX) based on the conserved domains and phylogenetic analysis. The number of members in the different classes ranged from 2 to 24, and they usually varied in terms of exon‒intron distribution pattern and length. There were 20 conserved motifs found in 115 PeHBs, with motif 1 being the most common. Gene ontology (GO) analysis showed that PeHBs had diverse molecular functions, with 19 PeHBs being annotated as having xylem development, xylem, and phloem pattern formation functions. Co-expression network analysis showed that 10 of the 19 PeHBs had co-expression correlations, and three members of the KNOX class were hub proteins that interacted with other transcription factors (TFs) such as MYB, bHLH, and OVATE, which were associated with lignin synthesis. Yeast two-hybridization results further proved that PeHB037 (BEL class) interacted with PeHB057 (KNOX class). Transcriptome expression profiling indicated that all PeHBs except PeHB017 were expressed in at least one of the seven tissues of moso bamboo, and 90 PeHBs were expressed in all the tissues. The qRT-PCR results of the 19 PeHBs showed that most of them were upregulated in shoots as the height increased. Moreover, a KNOX binding site was found in the promoters of the key genes involved in lignin synthesis such as Pe4CL, PeC3H, PeCCR, and PeCOMT, which had positive expression correlations with five KNOX genes. Similar results were found in winter bamboo shoots with prolonged storage time, which was consistent with the degree of lignification. These results provide basic data on PeHBs in moso bamboo, which will be helpful for future functional research on PeHBs with positive regulatory roles in the process of lignification. Full article
Open AccessArticle
Evaluating Iso-Mukaadial Acetate and Ursolic Acid Acetate as Plasmodium falciparum Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase Inhibitors
Biomolecules 2019, 9(12), 861; https://doi.org/10.3390/biom9120861 - 11 Dec 2019
Viewed by 121
Abstract
To date, Plasmodium falciparum is one of the most lethal strains of the malaria parasite. P. falciparum lacks the required enzymes to create its own purines via the de novo pathway, thereby making Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase (PfHGXPT) a crucial enzyme [...] Read more.
To date, Plasmodium falciparum is one of the most lethal strains of the malaria parasite. P. falciparum lacks the required enzymes to create its own purines via the de novo pathway, thereby making Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase (PfHGXPT) a crucial enzyme in the malaria life cycle. Recently, studies have described iso-mukaadial acetate and ursolic acid acetate as promising antimalarials. However, the mode of action is still unknown, thus, the current study sought to investigate the selective inhibitory and binding actions of iso-mukaadial acetate and ursolic acid acetate against recombinant PfHGXPT using in-silico and experimental approaches. Recombinant PfHGXPT protein was expressed using E. coli BL21 cells and homogeneously purified by affinity chromatography. Experimentally, iso-mukaadial acetate and ursolic acid acetate, respectively, demonstrated direct inhibitory activity towards PfHGXPT in a dose-dependent manner. The binding affinity of iso-mukaadial acetate and ursolic acid acetate on the PfHGXPT dissociation constant (KD), where it was found that 0.0833 µM and 2.8396 µM, respectively, are indicative of strong binding. The mode of action for the observed antimalarial activity was further established by a molecular docking study. The molecular docking and dynamics simulations show specific interactions and high affinity within the binding pocket of Plasmodium falciparum and human hypoxanthine-guanine phosphoribosyl transferases. The predicted in silico absorption, distribution, metabolism and excretion/toxicity (ADME/T) properties predicted that the iso-mukaadial acetate ligand may follow the criteria for orally active drugs. The theoretical calculation derived from ADME, molecular docking and dynamics provide in-depth information into the structural basis, specific bonding and non-bonding interactions governing the inhibition of malarial. Taken together, these findings provide a basis for the recommendation of iso-mukaadial acetate and ursolic acid acetate as high-affinity ligands and drug candidates against PfHGXPT. Full article
Open AccessReview
New Insights into the Control of Cell Fate Choices and Differentiation by Retinoic Acid in Cranial, Axial and Caudal Structures
Biomolecules 2019, 9(12), 860; https://doi.org/10.3390/biom9120860 - 11 Dec 2019
Viewed by 116
Abstract
Retinoic acid (RA) signaling is an important regulator of chordate development. RA binds to nuclear RA receptors that control the transcriptional activity of target genes. Controlled local degradation of RA by enzymes of the Cyp26a gene family contributes to the establishment of transient [...] Read more.
Retinoic acid (RA) signaling is an important regulator of chordate development. RA binds to nuclear RA receptors that control the transcriptional activity of target genes. Controlled local degradation of RA by enzymes of the Cyp26a gene family contributes to the establishment of transient RA signaling gradients that control patterning, cell fate decisions and differentiation. Several steps in the lineage leading to the induction and differentiation of neuromesodermal progenitors and bone-producing osteogenic cells are controlled by RA. Changes to RA signaling activity have effects on the formation of the bones of the skull, the vertebrae and the development of teeth and regeneration of fin rays in fish. This review focuses on recent advances in these areas, with predominant emphasis on zebrafish, and highlights previously unknown roles for RA signaling in developmental processes. Full article
(This article belongs to the Special Issue Retinoids in Embryonic Development)
Open AccessArticle
Glucose Uptake Stimulatory and PTP1B Inhibitory Activities of Pimarane Diterpenes from Orthosiphon stamineus Benth
Biomolecules 2019, 9(12), 859; https://doi.org/10.3390/biom9120859 - 11 Dec 2019
Viewed by 131
Abstract
Seven pimarane diterpenes (17) were isolated from Orthosiphon stamineus Benth. by assay-guided isolation. All of the isolates possessed a 2-deoxy-2-((7-nitro-2,1,3-benzoxadiazol-4-yl)amino)-d-glucose uptake effect in 3T3-L1 adipocytes at concentrations of 5 and 10 μM. Most of them showed potent inhibition against [...] Read more.
Seven pimarane diterpenes (17) were isolated from Orthosiphon stamineus Benth. by assay-guided isolation. All of the isolates possessed a 2-deoxy-2-((7-nitro-2,1,3-benzoxadiazol-4-yl)amino)-d-glucose uptake effect in 3T3-L1 adipocytes at concentrations of 5 and 10 μM. Most of them showed potent inhibition against protein tyrosine phosphatase 1B with IC50 values ranging from 0.33 to 9.84 μM. In the kinetic study, all inhibition types were exposed for the examined potencies, including mixed-competitive (1), non-competitives (3 and 5), competitive (6), and uncompetitive (7). The results suggested that O. stamineus and its pimarane diterpenes might exert the hypoglycemic effect via the insulin signaling pathway targeting inhibition of protein tyrosine phosphatase 1B (PTP1B) activity. Full article
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Open AccessArticle
Herbal Extracts Incorporated into Shortbread Cookies: Impact on Color and Fat Quality of the Cookies
Biomolecules 2019, 9(12), 858; https://doi.org/10.3390/biom9120858 - 11 Dec 2019
Viewed by 126
Abstract
This study aimed at determining the effect of aqueous ethanolic extracts from lemon balm, hyssop and nettle, and butylated hydroxyanisole (BHA) on properties of shortbread cookies. This was achieved by instrumental measurements of color and sensory properties of the cookies directly after baking [...] Read more.
This study aimed at determining the effect of aqueous ethanolic extracts from lemon balm, hyssop and nettle, and butylated hydroxyanisole (BHA) on properties of shortbread cookies. This was achieved by instrumental measurements of color and sensory properties of the cookies directly after baking and by determination of peroxide (PV) and p-anisidine (p-AnV) values, and specific extinction coefficients (K232 and K268 values) for fat extracted from the cookies stored for 3 months at room temperature. Increase of the herbal extracts’ concentration from 0.02% to 0.2% in the cookies caused a reduction of L* (the brightness) and a* values (the red coordinate), while b* values (the yellow coordinate) increased when the cookies were enriched with lemon balm and nettle extracts. Among the cookies studied, those prepared with BHA and 0.1 and 0.2% addition of lemon balm extracts were characterized by the highest scores for aroma, taste, and overall acceptability. Incorporation of BHA and 0.02% hyssop extract into the cookies caused a decrease of PV values (the peroxide value) for fat extracted from the cookies after 3 months of their storage compared to a (control) sample without additives and produced the lowest K232 values. Changes in the p-AnV values for the fat samples studied occurred gradually and slowly during the storage and the obtained values were lower compared to the control sample. All of the studied fat samples also showed a higher ability to scavenge DPPH radicals than the control sample. Considering both PV and p-AnV values as indicators of fat oxidation, BHA protected fat extracted from cookies against oxidation better than the herbal extracts used. Full article
(This article belongs to the Section Natural and Bio-inspired Molecules)
Open AccessReview
Fatty Acids of Marine Mollusks: Impact of Diet, Bacterial Symbiosis and Biosynthetic Potential
Biomolecules 2019, 9(12), 857; https://doi.org/10.3390/biom9120857 - 11 Dec 2019
Viewed by 107
Abstract
The n-3 and n-6 polyunsaturated fatty acid (PUFA) families are essential for important physiological processes. Their major source are marine ecosystems. The fatty acids (FAs) from phytoplankton, which are the primary producer of organic matter and PUFAs, are transferred into consumers via food [...] Read more.
The n-3 and n-6 polyunsaturated fatty acid (PUFA) families are essential for important physiological processes. Their major source are marine ecosystems. The fatty acids (FAs) from phytoplankton, which are the primary producer of organic matter and PUFAs, are transferred into consumers via food webs. Mollusk FAs have attracted the attention of researchers that has been driven by their critical roles in aquatic ecology and their importance as sources of essential PUFAs. The main objective of this review is to focus on the most important factors and causes determining the biodiversity of the mollusk FAs, with an emphasis on the key relationship of these FAs with the food spectrum and trophic preference. The marker FAs of trophic sources are also of particular interest. The discovery of new symbioses involving invertebrates and bacteria, which are responsible for nutrition of the host, deserves special attention. The present paper also highlights recent research into the molecular and biochemical mechanisms of PUFA biosynthesis in marine mollusks. The biosynthetic capacities of marine mollusks require a well-grounded evaluation. Full article
(This article belongs to the Special Issue Fatty Acids in Natural Ecosystems and Human Nutrition)
Open AccessReview
Medical Therapy of Patients Contaminated with Radioactive Cesium or Iodine
Biomolecules 2019, 9(12), 856; https://doi.org/10.3390/biom9120856 - 11 Dec 2019
Viewed by 118
Abstract
Follow-up studies after the Chernobyl and Fukushima accidents have shown that 137Cs and 131I made up the major amount of harmful contaminants in the atmospheric dispersion and fallout. Other potential sources for such radionuclide exposure may be terrorist attacks, e.g., via [...] Read more.
Follow-up studies after the Chernobyl and Fukushima accidents have shown that 137Cs and 131I made up the major amount of harmful contaminants in the atmospheric dispersion and fallout. Other potential sources for such radionuclide exposure may be terrorist attacks, e.g., via contamination of drinking water reservoirs. A primary purpose of radionuclide mobilization is to minimize the radiation dose. Rapid initiation of treatment of poisoned patients is imperative after a contaminating event. Internal contamination with radioactive material can expose patients to prolonged radiation, thus leading to short- and long-term clinical consequences. After the patient’s emergency conditions are addressed, the treating physicians and assisting experts should assess the amount of radioactive material that has been internalized. This evaluation should include estimation of the radiation dose that is delivered and the specific radionuclides inside the body. These complex assessments warrant the reliance on a multidisciplinary approach that incorporates regional experts in radiation medicine and emergencies. Regional hospitals should have elaborated strategies for the handling of radiation emergencies. If radioactive cesium is a significant pollutant, Prussian blue is the approved antidote for internal detoxification. Upon risks of radioiodine exposure, prophylactic or immediate treatment with potassium iodide tablets is recommended. Chelators developed from calcium salts have been studied for gastrointestinal trapping and enhanced mobilization after strontium exposure. Full article
(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)
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Open AccessArticle
The Environment Is a Key Factor in Determining the Anti-Amyloid Efficacy of EGCG
Biomolecules 2019, 9(12), 855; https://doi.org/10.3390/biom9120855 - 11 Dec 2019
Viewed by 135
Abstract
Millions of people around the world suffer from amyloid-related disorders, including Alzheimer’s and Parkinson’s diseases. Despite significant and sustained efforts, there are still no disease-modifying drugs available for the majority of amyloid-related disorders, and the overall failure rate in clinical trials is very [...] Read more.
Millions of people around the world suffer from amyloid-related disorders, including Alzheimer’s and Parkinson’s diseases. Despite significant and sustained efforts, there are still no disease-modifying drugs available for the majority of amyloid-related disorders, and the overall failure rate in clinical trials is very high, even for compounds that show promising anti-amyloid activity in vitro. In this study, we demonstrate that even small changes in the chemical environment can strongly modulate the inhibitory effects of anti-amyloid compounds. Using one of the best-established amyloid inhibitory compounds, epigallocatechin-3-gallate (EGCG), as an example, and two amyloid-forming proteins, insulin and Parkinson’s disease-related α -synuclein, we shed light on the previously unexplored sensitivity to solution conditions of the action of this compound on amyloid fibril formation. In the case of insulin, we show that the classification of EGCG as an amyloid inhibitor depends on the experimental conditions select, on the method used for the evaluation of the efficacy, and on whether or not EGCG is allowed to oxidise before the experiment. For α -synuclein, we show that a small change in pH value, from 7 to 6, transforms EGCG from an efficient inhibitor to completely ineffective, and we were able to explain this behaviour by the increased stability of EGCG against oxidation at pH 6. Full article
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Open AccessReview
The Role of the Ω-Loop in Regulation of the Catalytic Activity of TEM-Type β-Lactamases
Biomolecules 2019, 9(12), 854; https://doi.org/10.3390/biom9120854 - 11 Dec 2019
Viewed by 136
Abstract
Bacterial resistance to β-lactams, the most commonly used class of antibiotics, poses a global challenge. This resistance is caused by the production of bacterial enzymes that are termed β-lactamases (βLs). The evolution of serine-class A β-lactamases from penicillin-binding proteins (PBPs) is related to [...] Read more.
Bacterial resistance to β-lactams, the most commonly used class of antibiotics, poses a global challenge. This resistance is caused by the production of bacterial enzymes that are termed β-lactamases (βLs). The evolution of serine-class A β-lactamases from penicillin-binding proteins (PBPs) is related to the formation of the Ω-loop at the entrance to the enzyme’s active site. In this loop, the Glu166 residue plays a key role in the two-step catalytic cycle of hydrolysis. This residue in TEM–type β-lactamases, together with Asn170, is involved in the formation of a hydrogen bonding network with a water molecule, leading to the deacylation of the acyl–enzyme complex and the hydrolysis of the β-lactam ring of the antibiotic. The activity exhibited by the Ω-loop is attributed to the positioning of its N-terminal residues near the catalytically important residues of the active site. The structure of the Ω-loop of TEM-type β-lactamases is characterized by low mutability, a stable topology, and structural flexibility. All of the revealed features of the Ω-loop, as well as the mechanisms related to its involvement in catalysis, make it a potential target for novel allosteric inhibitors of β-lactamases. Full article
(This article belongs to the Special Issue Beta-Lactamases: Sequence, Structure, Function, and Inhibition)
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Open AccessArticle
Lipid Membrane Adsorption Determines Photodynamic Efficiency of β-Imidazolyl-Substituted Porphyrins
Biomolecules 2019, 9(12), 853; https://doi.org/10.3390/biom9120853 - 10 Dec 2019
Viewed by 141
Abstract
Photosensitizers (PSs) represent a group of molecules capable of generating reactive oxygen species (ROS), such as singlet oxygen (SO); thus, they are considered to be promising agents for anti-cancer therapy. The enhancement of the photodynamic efficiency of these compounds requires increasing the PS [...] Read more.
Photosensitizers (PSs) represent a group of molecules capable of generating reactive oxygen species (ROS), such as singlet oxygen (SO); thus, they are considered to be promising agents for anti-cancer therapy. The enhancement of the photodynamic efficiency of these compounds requires increasing the PS activity in the cancer cell milieu and exactly at the target cells. In the present work, we report the synthesis, lipid membrane binding and photodynamic activity of three novel cationic PSs based on β-imidazolyl-substituted porphyrin and its Zn(II) and In(III) complexes (1H2, 1Zn and 1In). Comparison of the behavior of the investigated porphyrins at the bilayer lipid membrane (BLM) demonstrated the highest adsorption for the 1In complex and the lowest one for 1Zn. The photodynamic efficiency of these porphyrins was evaluated by determining the oxidation rate of the styryl dye, di-4-ANEPPS, incorporated into the lipid membrane. These rates were proportional to the surface density (SD) of the porphyrin molecules at the BLM and were roughly the same for all three porphyrins. This indicates that the adsorption of these porphyrins at the BLM determines their photodynamic efficiency rather than the extinction or quantum yield of singlet oxygen. Full article
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Open AccessArticle
Molecular Dynamics Simulation of Transmembrane Transport of Chloride Ions in Mutants of Channelrhodopsin
Biomolecules 2019, 9(12), 852; https://doi.org/10.3390/biom9120852 - 10 Dec 2019
Viewed by 129
Abstract
Channelrhodopsins (ChRs) are light-gated transmembrane cation channels which are widely used for optogenetic technology. Replacing glutamate located at the central gate of the ion channel with positively charged amino acid residues will reverse ion selectivity and allow anion conduction. The structures and properties [...] Read more.
Channelrhodopsins (ChRs) are light-gated transmembrane cation channels which are widely used for optogenetic technology. Replacing glutamate located at the central gate of the ion channel with positively charged amino acid residues will reverse ion selectivity and allow anion conduction. The structures and properties of the ion channel, the transport of chloride, and potential of mean force (PMF) of the chimera protein (C1C2) and its mutants, EK-TC, ER-TC and iChloC, were investigated by molecular dynamics simulation. The results show that the five-fold mutation in E122Q-E129R-E140S-D195N-T198C (iChloC) increases the flexibility of the transmembrane channel protein better than the double mutations in EK-TC and ER-TC, and results in an expanded ion channel pore size and decreased steric resistance. The iChloC mutant was also found to have a higher affinity for chloride ions and, based on surface electrostatic potential analysis, provides a favorable electrostatic environment for anion conduction. The PMF free energy curves revealed that high affinity Cl binding sites are generated near the central gate of the three mutant proteins. The energy barriers for the EK-TC and ER-TC were found to be much higher than that of iChloC. The results suggest that the transmembrane ion channel of iChloC protein is better at facilitating the capture and transport of chloride ions. Full article
(This article belongs to the Special Issue Advances in Membrane Proteins)
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Open AccessArticle
Alcohol Metabolism Potentiates HIV-Induced Hepatotoxicity: Contribution to End-Stage Liver Disease
Biomolecules 2019, 9(12), 851; https://doi.org/10.3390/biom9120851 - 10 Dec 2019
Viewed by 115
Abstract
In an era of improved survival due to modern antiretroviral therapy, liver disease has become a major cause of morbidity and mortality, resulting in death in 15–17% of human immunodeficiency virus (HIV)-infected patients. Alcohol enhances HIV-mediated liver damage and promotes the progression to [...] Read more.
In an era of improved survival due to modern antiretroviral therapy, liver disease has become a major cause of morbidity and mortality, resulting in death in 15–17% of human immunodeficiency virus (HIV)-infected patients. Alcohol enhances HIV-mediated liver damage and promotes the progression to advanced fibrosis and cirrhosis. However, the mechanisms behind these events are uncertain. Here, we hypothesize that ethanol metabolism potentiates accumulation of HIV in hepatocytes, causing oxidative stress and intensive apoptotic cell death. Engulfment of HIV-containing apoptotic hepatocytes by non-parenchymal cells (NPCs) triggers their activation and liver injury progression. This study was performed on primary human hepatocytes and Huh7.5-CYP cells infected with HIV-1ADA, and major findings were confirmed by pilot data obtained on ethanol-fed HIV-injected chimeric mice with humanized livers. We demonstrated that ethanol exposure potentiates HIV accumulation in hepatocytes by suppressing HIV degradation by lysosomes and proteasomes. This leads to increased oxidative stress and hepatocyte apoptosis. Exposure of HIV-infected apoptotic hepatocytes to NPCs activates the inflammasome in macrophages and pro-fibrotic genes in hepatic stellate cells. We conclude that while HIV and ethanol metabolism-triggered apoptosis clears up HIV-infected hepatocytes, continued generation of HIV-expressing apoptotic bodies may be detrimental for progression of liver inflammation and fibrosis due to constant activation of NPCs. Full article
(This article belongs to the collection Multi-Organ Alcohol-Related Damage: Mechanisms and Treatment)
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Open AccessReview
Modulatory Mechanisms of the NLRP3 Inflammasomes in Diabetes
Biomolecules 2019, 9(12), 850; https://doi.org/10.3390/biom9120850 - 09 Dec 2019
Viewed by 206
Abstract
The inflammasome is a multiprotein complex that acts to enhance inflammatory responses by promoting the production and secretion of key cytokines. The best-known inflammasome is the NLRP3 (nucleotide-binding oligomerization domain-like receptor [NLR] family pyrin domain-containing 3) inflammasome. The evidence has shown that the [...] Read more.
The inflammasome is a multiprotein complex that acts to enhance inflammatory responses by promoting the production and secretion of key cytokines. The best-known inflammasome is the NLRP3 (nucleotide-binding oligomerization domain-like receptor [NLR] family pyrin domain-containing 3) inflammasome. The evidence has shown that the NLRP3 inflammasome, IL-1β, thioredoxin-interacting protein (TXNIP), and pyroptosis play vital roles in the development of diabetes. This review summarizes the regulation of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) by NLRP3 via modulation of glucose tolerance, insulin resistance, inflammation, and apoptosis mediated by endoplasmic reticulum stress in adipose tissue. Moreover, NLRP3 participates in intestinal homeostasis and inflammatory conditions, and NLRP3-deficient mice experience intestinal lesions. The diversity of an individual’s gut microbiome and the resultant microbial metabolites determines the extent of their involvement in the physiological and pathological mechanisms within the gut. As such, further study of the interaction between the NLRP3 inflammasome and the complex intestinal environment in disease development is warranted to discover novel therapies for the treatment of diabetes. Full article
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Open AccessArticle
Brassinosteroids Induce Strong, Dose-Dependent Inhibition of Etiolated Pea Seedling Growth Correlated with Ethylene Production
Biomolecules 2019, 9(12), 849; https://doi.org/10.3390/biom9120849 - 09 Dec 2019
Viewed by 183
Abstract
We have recently discovered that brassinosteroids (BRs) can inhibit the growth of etiolated pea seedlings dose-dependently in a similar manner to the ‘triple response’ induced by ethylene. We demonstrate here that the growth inhibition of etiolated pea shoots strongly correlates with increases in [...] Read more.
We have recently discovered that brassinosteroids (BRs) can inhibit the growth of etiolated pea seedlings dose-dependently in a similar manner to the ‘triple response’ induced by ethylene. We demonstrate here that the growth inhibition of etiolated pea shoots strongly correlates with increases in ethylene production, which also responds dose-dependently to applied BRs. We assessed the biological activities of two natural BRs on pea seedlings, which are excellent material as they grow rapidly, and respond both linearly and uni-phasically to applied BRs. We then compared the BRs’ inhibitory effects on growth, and induction of ethylene and ACC (1-aminocyclopropane-1-carboxylic acid) production, to those of representatives of other phytohormone classes (cytokinins, auxins, and gibberellins). Auxin induced ca. 50-fold weaker responses in etiolated pea seedlings than brassinolide, and the other phytohormones induced much weaker (or opposite) responses. Following the optimization of conditions for determining ethylene production after BR treatment, we found a positive correlation between BR bioactivity and ethylene production. Finally, we optimized conditions for pea growth responses and developed a new, highly sensitive, and convenient bioassay for BR activity. Full article
(This article belongs to the Special Issue Phytohormones)
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Open AccessArticle
Characterization of the Interaction of Neuropathy Target Esterase with the Endoplasmic Reticulum and Lipid Droplets
Biomolecules 2019, 9(12), 848; https://doi.org/10.3390/biom9120848 - 09 Dec 2019
Viewed by 198
Abstract
: Neuropathy target esterase (NTE) is an endoplasmic reticulum (ER)-localized phospholipase that deacylates phosphatidylcholine (PC) and lysophosphatidylcholine (LPC). Loss-of-function mutations in the human NTE gene have been associated with a spectrum of neurodegenerative disorders such as hereditary spastic paraplegia, ataxia and chorioretinal dystrophy. [...] Read more.
: Neuropathy target esterase (NTE) is an endoplasmic reticulum (ER)-localized phospholipase that deacylates phosphatidylcholine (PC) and lysophosphatidylcholine (LPC). Loss-of-function mutations in the human NTE gene have been associated with a spectrum of neurodegenerative disorders such as hereditary spastic paraplegia, ataxia and chorioretinal dystrophy. Despite this, little is known about structure–function relationships between NTE protein domains, enzymatic activity and the interaction with cellular organelles. In the current study we show that the C-terminal region of NTE forms a catalytically active domain that exhibits high affinity for lipid droplets (LDs), cellular storage organelles for triacylglycerol (TAG), which have been recently implicated in the progression of neurodegenerative diseases. Ectopic expression of the C domain in cultured cells decreases cellular PC, elevates TAG and induces LD clustering. LD interactions of NTE are inhibited by default by a non-enzymatic regulatory (R) region with three putative nucleotide monophosphate binding sites. Together with a N-terminal TMD the R region promotes proper distribution of the catalytic C-terminal region to the ER network. Taken together, our data indicate that NTE may exhibit dynamic interactions with the ER and LDs depending on the interplay of its functional regions. Mutations that disrupt this interplay may contribute to NTE-associated disorders by affecting NTE positioning. Full article
(This article belongs to the Section Biochemistry)
Open AccessReview
The Quest for Phenolic Compounds from Macroalgae: A Review of Extraction and Identification Methodologies
Biomolecules 2019, 9(12), 847; https://doi.org/10.3390/biom9120847 - 09 Dec 2019
Viewed by 137
Abstract
The current interest of the scientific community for the exploitation of high-value compounds from macroalgae is related to the increasing knowledge of their biological activities and health benefits. Macroalgae phenolic compounds, particularly phlorotannins, have gained particular attention due to their specific bioactivities, including [...] Read more.
The current interest of the scientific community for the exploitation of high-value compounds from macroalgae is related to the increasing knowledge of their biological activities and health benefits. Macroalgae phenolic compounds, particularly phlorotannins, have gained particular attention due to their specific bioactivities, including antioxidant, antiproliferative, or antidiabetic. Notwithstanding, the characterization of macroalgae phenolic compounds is a multi-step task, with high challenges associated with their isolation and characterization, due to the highly complex and polysaccharide-rich matrix of macroalgae. Therefore, this fraction is far from being fully explored. In fact, a critical revision of the extraction and characterization methodologies already used in the analysis of phenolic compounds from macroalgae is lacking in the literature, and it is of uttermost importance to compile validated methodologies and discourage misleading practices. The aim of this review is to discuss the state-of-the-art of phenolic compounds already identified in green, red, and brown macroalgae, reviewing their structural classification, as well as critically discussing extraction methodologies, chromatographic separation techniques, and the analytical strategies for their characterization, including information about structural identification techniques and key spectroscopic profiles. For the first time, mass spectrometry data of phlorotannins, a chemical family quite exclusive of macroalgae, is compiled and discussed. Full article
(This article belongs to the Section Natural and Bio-inspired Molecules)
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Open AccessReview
Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer
Biomolecules 2019, 9(12), 846; https://doi.org/10.3390/biom9120846 - 09 Dec 2019
Viewed by 184
Abstract
Interest has grown in studying the possible use of well-known anti-diabetic drugs as anti-cancer agents individually or in combination with, frequently used, chemotherapeutic agents and/or radiation, owing to the fact that diabetes heightens the risk, incidence, and rapid progression of cancers, including breast [...] Read more.
Interest has grown in studying the possible use of well-known anti-diabetic drugs as anti-cancer agents individually or in combination with, frequently used, chemotherapeutic agents and/or radiation, owing to the fact that diabetes heightens the risk, incidence, and rapid progression of cancers, including breast cancer, in an individual. In this regard, metformin (1, 1-dimethylbiguanide), well known as ‘Glucophage’ among diabetics, was reported to be cancer preventive while also being a potent anti-proliferative and anti-cancer agent. While meta-analysis studies reported a lower risk and incidence of breast cancer among diabetic individuals on a metformin treatment regimen, several in vitro, pre-clinical, and clinical studies reported the efficacy of using metformin individually as an anti-cancer/anti-tumor agent or in combination with chemotherapeutic drugs or radiation in the treatment of different forms of breast cancer. However, unanswered questions remain with regards to areas such as cancer treatment specific therapeutic dosing of metformin, specificity to cancer cells at high concentrations, resistance to metformin therapy, efficacy of combinatory therapeutic approaches, post-therapeutic relapse of the disease, and efficacy in cancer prevention in non-diabetic individuals. In the current article, we discuss the biology of metformin and its molecular mechanism of action, the existing cellular, pre-clinical, and clinical studies that have tested the anti-tumor potential of metformin as a potential anti-cancer/anti-tumor agent in breast cancer therapy, and outline the future prospects and directions for a better understanding and re-purposing of metformin as an anti-cancer drug in the treatment of breast cancer. Full article
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Open AccessArticle
Transthyretin Anti-Amyloidogenic and Fibril Disrupting Activities of Bacopa monnieri (L.) Wettst (Brahmi) Extract
Biomolecules 2019, 9(12), 845; https://doi.org/10.3390/biom9120845 - 09 Dec 2019
Viewed by 138
Abstract
The homotetrameric plasma protein transthyretin (TTR), is responsible for a series of debilitating and often fatal disorders in humans known as transthyretin amyloidosis. Currently, there is no cure for TTR amyloidosis and treatment options are rare. Thus, the identification and development of effective [...] Read more.
The homotetrameric plasma protein transthyretin (TTR), is responsible for a series of debilitating and often fatal disorders in humans known as transthyretin amyloidosis. Currently, there is no cure for TTR amyloidosis and treatment options are rare. Thus, the identification and development of effective and safe therapeutic agents remain a research imperative. The objective of this study was to determine the effectiveness of Bacopa monnieri extract (BME) in the modulation of TTR amyloidogenesis and disruption of preformed fibrils. Using aggregation assays and transmission electron microscopy, it was found that BME abrogated the formation of human TTR aggregates and mature fibrils but did not dis-aggregate pre-formed fibrils. Through acid-mediated and urea-mediated denaturation assays, it was revealed that BME mitigated the dissociation of folded human TTR and L55P TTR into monomers. ANS binding and glutaraldehyde cross-linking assays showed that BME binds at the thyroxine-binding site and possibly enhanced the quaternary structural stability of native TTR. Together, our results suggest that BME bioactives prevented the formation of TTR fibrils by attenuating the disassembly of tetramers into monomers. These findings open up the possibility of further exploration of BME as a potential resource of valuable anti-TTR amyloidosis therapeutic ingredients. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle
Pretreatment of Wheat Straw with Phosphoric Acid and Hydrogen Peroxide to Simultaneously Facilitate Cellulose Digestibility and Modify Lignin as Adsorbents
Biomolecules 2019, 9(12), 844; https://doi.org/10.3390/biom9120844 - 08 Dec 2019
Viewed by 246
Abstract
Effective valorization of lignin is crucial to achieve a sustainable, economic and competitive biorefinery of lignocellulosic biomass. In this work, an integrated process was proposed based on a concentrated phosphoric acid plus hydrogen peroxide (PHP) pretreatment to simultaneously facilitate cellulose digestibility and modify [...] Read more.
Effective valorization of lignin is crucial to achieve a sustainable, economic and competitive biorefinery of lignocellulosic biomass. In this work, an integrated process was proposed based on a concentrated phosphoric acid plus hydrogen peroxide (PHP) pretreatment to simultaneously facilitate cellulose digestibility and modify lignin as adsorbent. As a dominant constitutor of PHP pretreatment, H2O2 input and its influence on the overall fractionation/lignin modification performance was thoroughly investigated. Results indicated that wheat straw was fractionated more efficiently by increasing the H2O2 input. H2O2 input had a significant influence on the digestibility of the obtained cellulose-rich fraction whereby almost 100.0% cellulose-glucose conversion can be achieved even with only 0.88% H2O2 input. Besides, the adsorption capacity of lignin on MB was improved (74.3 to 210.1 mg g−1) due to the oxidative-modification in PHP pretreatment with H2O2 inputs. Regression analysis indicated that –COOH groups mainly governed the lignin adsorption (R2 = 0.946), which displayed the considerable adsorption capacities for typical cationic substances. This work shows a promising way to integrate the lignin modification concept into the emerging PHP pretreatment process with the dual goal of both cellulose utilization and lignin valorization. Full article
(This article belongs to the Special Issue Lignocellulosic Biomass Catalysis)
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Open AccessReview
Insights into the Chemical Biology of Childhood Embryonal Solid Tumors by NMR-Based Metabolomics
Biomolecules 2019, 9(12), 843; https://doi.org/10.3390/biom9120843 - 08 Dec 2019
Viewed by 221
Abstract
Most childhood cancers occur as isolated cases and show very different biological behavior when compared with cancers in adults. There are some solid tumors that occur almost exclusively in children among which stand out the embryonal solid tumors. These cancers main types are [...] Read more.
Most childhood cancers occur as isolated cases and show very different biological behavior when compared with cancers in adults. There are some solid tumors that occur almost exclusively in children among which stand out the embryonal solid tumors. These cancers main types are neuroblastoma, nephroblastoma (Wilms tumors), retinoblastoma and hepatoblastomas and tumors of the central nervous system (CNS). Embryonal solid tumors represent a heterogeneous group of cancers supposedly derived from undifferentiated cells, with histological features that resemble tissues of origin during embryogenesis. This key observation suggests that tumorigenesis might begin during early fetal or child life due to the errors in growth or pathways differentiation. There are not many literature data on genomic, transcriptomic, epigenetic, proteomic, or metabolomic differences in these types of cancers when compared to the omics- used in adult cancer research. Still, metabolomics by nuclear magnetic resonance (NMR) in childhood embryonal solid tumors research can contribute greatly to understand better metabolic pathways alterations and biology of the embryonal solid tumors and potential to be used in clinical applications. Different types of samples, such as tissues, cells, biofluids, mostly blood plasma and serum, can be analyzed by NMR to detect and identify cancer metabolic signatures and validated biomarkers using enlarged group of samples. The literature search for biomarkers points to around 20–30 compounds that could be associated with pediatric cancer as well as metastasis. Full article
(This article belongs to the Section Molecular Medicine)
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