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Biomolecules, Volume 10, Issue 7 (July 2020) – 33 articles

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Open AccessReview
UPF1-Mediated RNA Decay—Danse Macabre in a Cloud
Biomolecules 2020, 10(7), 999; https://doi.org/10.3390/biom10070999 (registering DOI) - 04 Jul 2020
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Abstract
Nonsense-mediated RNA decay (NMD) is the prototype example of a whole family of RNA decay pathways that unfold around a common central effector protein called UPF1. While NMD in yeast appears to be a linear pathway, NMD in higher eukaryotes is a multifaceted [...] Read more.
Nonsense-mediated RNA decay (NMD) is the prototype example of a whole family of RNA decay pathways that unfold around a common central effector protein called UPF1. While NMD in yeast appears to be a linear pathway, NMD in higher eukaryotes is a multifaceted phenomenon with high variability with respect to substrate RNAs, degradation efficiency, effector proteins and decay-triggering RNA features. Despite increasing knowledge of the mechanistic details, it seems ever more difficult to define NMD and to clearly distinguish it from a growing list of other UPF1-mediated RNA decay pathways (UMDs). With a focus on mammalian, we here critically examine the prevailing NMD models and the gaps and inconsistencies in these models. By exploring the minimal requirements for NMD and other UMDs, we try to elucidate whether they are separate and definable pathways, or rather variations of the same phenomenon. Finally, we suggest that the operating principle of the UPF1-mediated decay family could be considered similar to that of a computing cloud providing a flexible infrastructure with rapid elasticity and dynamic access according to specific user needs Full article
(This article belongs to the Special Issue Ribonucleoprotein Particles (RNPs): From Structure to Function)
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Open AccessReview
Physiopathology of the Permeability Transition Pore: Molecular Mechanisms in Human Pathology
Biomolecules 2020, 10(7), 998; https://doi.org/10.3390/biom10070998 (registering DOI) - 04 Jul 2020
Viewed by 165
Abstract
Mitochondrial permeability transition (MPT) is the sudden loss in the permeability of the inner mitochondrial membrane (IMM) to low-molecular-weight solutes. Due to osmotic forces, MPT is paralleled by a massive influx of water into the mitochondrial matrix, eventually leading to the structural collapse [...] Read more.
Mitochondrial permeability transition (MPT) is the sudden loss in the permeability of the inner mitochondrial membrane (IMM) to low-molecular-weight solutes. Due to osmotic forces, MPT is paralleled by a massive influx of water into the mitochondrial matrix, eventually leading to the structural collapse of the organelle. Thus, MPT can initiate outer-mitochondrial-membrane permeabilization (MOMP), promoting the activation of the apoptotic caspase cascade and caspase-independent cell-death mechanisms. The induction of MPT is mostly dependent on mitochondrial reactive oxygen species (ROS) and Ca2+, but is also dependent on the metabolic stage of the affected cell and signaling events. Therefore, since its discovery in the late 1970s, the role of MPT in human pathology has been heavily investigated. Here, we summarize the most significant findings corroborating a role for MPT in the etiology of a spectrum of human diseases, including diseases characterized by acute or chronic loss of adult cells and those characterized by neoplastic initiation. Full article
(This article belongs to the Special Issue Mitochondrial Transport Proteins)
Open AccessArticle
Chemopreventive Property of Sencha Tea Extracts towards Sensitive and Multidrug-Resistant Leukemia and Multiple Myeloma Cells
Biomolecules 2020, 10(7), 1000; https://doi.org/10.3390/biom10071000 (registering DOI) - 04 Jul 2020
Viewed by 163
Abstract
The popular beverage green tea possesses chemopreventive activity against various types of tumors. However, the effects of its chemopreventive effect on hematological malignancies have not been defined. In the present study, we evaluated antitumor efficacies of a specific green tea, sencha tea, on [...] Read more.
The popular beverage green tea possesses chemopreventive activity against various types of tumors. However, the effects of its chemopreventive effect on hematological malignancies have not been defined. In the present study, we evaluated antitumor efficacies of a specific green tea, sencha tea, on sensitive and multidrug-resistant leukemia and a panel of nine multiple myelomas (MM) cell lines. We found that sencha extracts induced cytotoxicity in leukemic cells and MM cells to different extents, yet its effect on normal cells was limited. Furthermore, sencha extracts caused G2/M and G0/G1 phase arrest during cell cycle progression in CCRF/CEM and KMS-12-BM cells, respectively. Specifically, sencha-MeOH/H2O extracts induced apoptosis, ROS, and MMP collapse on both CCRF/CEM and KMS-12-BM cells. The analysis with microarray and COMPARE in 53 cell lines of the NCI panel revealed diverse functional groups, including cell morphology, cellular growth and proliferation, cell cycle, cell death, and survival, which were closely associated with anti-tumor effects of sencha tea. It is important to note that PI3K/Akt and NF-κB pathways were the top two dominant networks by ingenuity pathway analysis. We demonstrate here the multifactorial modes of action of sencha tea leading to chemopreventive effects of sencha tea against cancer. Full article
(This article belongs to the Section Biochemistry)
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Open AccessArticle
CMH-Small Molecule Docks into SIRT1, Elicits Human IPF-Lung Fibroblast Cell Death, Inhibits Ku70-deacetylation, FLIP and Experimental Pulmonary Fibrosis
Biomolecules 2020, 10(7), 997; https://doi.org/10.3390/biom10070997 (registering DOI) - 02 Jul 2020
Viewed by 183
Abstract
Regenerative capacity in vital organs is limited by fibrosis propensity. Idiopathic pulmonary fibrosis (IPF), a progressive lung disease linked with aging, is a classic example. In this study, we show that in flow cytometry, immunoblots (IB) and in lung sections, FLIP levels can [...] Read more.
Regenerative capacity in vital organs is limited by fibrosis propensity. Idiopathic pulmonary fibrosis (IPF), a progressive lung disease linked with aging, is a classic example. In this study, we show that in flow cytometry, immunoblots (IB) and in lung sections, FLIP levels can be regulated, in vivo and in vitro, through SIRT1 activity inhibition by CMH (4-(4-Chloro-2-methylphenoxy)-N-hydroxybutanamide), a small molecule that, as we determined here by structural biology calculations, docked into its nonhistone substrate Ku70-binding site. Ku70 immunoprecipitations and immunoblots confirmed our theory that Ku70-deacetylation, Ku70/FLIP complex, myofibroblast resistance to apoptosis, cell survival, and lung fibrosis in bleomycin-treated mice, are reduced and regulated by CMH. Thus, small molecules associated with SIRT1-mediated regulation of Ku70 deacetylation, affecting FLIP stabilization in fibrotic-lung myofibroblasts, may be a useful strategy, enabling tissue regeneration. Full article
Open AccessArticle
SIRT1 Deficiency, Specifically in Fibroblasts, Decreases Apoptosis Resistance and Is Associated with Resolution of Lung-Fibrosis
Biomolecules 2020, 10(7), 996; https://doi.org/10.3390/biom10070996 (registering DOI) - 02 Jul 2020
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Abstract
In contrast to normal regenerating tissue, resistance to Fas- and FasL-positive T cell-induced apoptosis were detected in myofibroblasts from fibrotic-lungs of humans and mice following bleomycin (BLM) exposure. In this study we show, decreased FLIP expression in lung-tissues with resolution of BLM-induced fibrosis [...] Read more.
In contrast to normal regenerating tissue, resistance to Fas- and FasL-positive T cell-induced apoptosis were detected in myofibroblasts from fibrotic-lungs of humans and mice following bleomycin (BLM) exposure. In this study we show, decreased FLIP expression in lung-tissues with resolution of BLM-induced fibrosis and in isolated-lung fibroblasts, with decreased resistance to apoptosis. Using a FLIP-expression vector or a shFLIP-RNA, we further confirmed the critical need for FLIP to regain/lose susceptibility of fibrotic-lung myofibroblast to Fas-induced apoptosis. Our study further show that FLIP is regulated by SIRT1 (Sirtuin 1) deacetylase. Chimeric mice, with SIRT1-deficiency in deacetylase domain (H355Y-Sirt1y/y), specifically in mesenchymal cells, were not only protected from BLM-induced lung fibrosis but, as assessed following Ku70 immunoprecipitation, had also decreased Ku70-deacetylation, decreasedKu70/FLIP complex, and decreased FLIP levels in their lung myofibroblasts. In addition, myofibroblasts isolated from lungs of BLM-treated miR34a-knockout mice, exposed to a miR34a mimic, which we found here to downregulate SIRT1 in the luciferase assay, had a decreased Ku70-deacetylation indicating decrease in SIRT1 activity. Thus, SIRT1 may mediate, miR34a-regulated, persistent FLIP levels by deacetylation of Ku70 in lung myofibroblasts, promoting resistance to cell-death and lung fibrosis. Full article
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Open AccessArticle
Hydrogen Sulfide Alleviates Anxiety, Motor, and Cognitive Dysfunctions in Rats with Maternal Hyperhomocysteinemia via Mitigation of Oxidative Stress
Biomolecules 2020, 10(7), 995; https://doi.org/10.3390/biom10070995 (registering DOI) - 02 Jul 2020
Viewed by 130
Abstract
Hydrogen sulfide (H2S) is endogenously produced from sulfur containing amino acids, including homocysteine and exerts neuroprotective effects. An increase of homocysteine during pregnancy impairs fetal growth and development of the offspring due to severe oxidative stress. We analyzed the effects of [...] Read more.
Hydrogen sulfide (H2S) is endogenously produced from sulfur containing amino acids, including homocysteine and exerts neuroprotective effects. An increase of homocysteine during pregnancy impairs fetal growth and development of the offspring due to severe oxidative stress. We analyzed the effects of the H2S donor—sodium hydrosulfide (NaHS) administered to female rats with hyperhomocysteinemia (hHcy) on behavioral impairments and levels of oxidative stress of their offspring. Rats born from females fed with control or high methionine diet, with or without H2S donor injections were investigated. Rats with maternal hHcy exhibit increased levels of total locomotor activity and anxiety, decreased muscle endurance and motor coordination, abnormalities of fine motor control, as well as reduced spatial memory and learning. Oxidative stress in brain tissues measured by activity of glutathione peroxidases and the level of malondialdehyde was higher in rats with maternal hHcy. Concentrations of H2S and the activity and expression of the H2S generating enzyme—cystathionine-beta synthase—were lower compared to the control group. Administration of the H2S donor to females with hHcy during pregnancy prevented behavioral alterations and oxidative stress of their offspring. The acquisition of behavioral together with biochemical studies will add to our knowledge about homocysteine neurotoxicity and proposes H2S as a potential agent for therapy of hHcy associated disorders. Full article
(This article belongs to the Special Issue Homocysteine: Biochemistry, Molecular Biology, and Role in Disease)
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Open AccessArticle
The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis
Biomolecules 2020, 10(7), 994; https://doi.org/10.3390/biom10070994 (registering DOI) - 02 Jul 2020
Viewed by 137
Abstract
Combining phytochemicals with chemotherapics is an emerging strategy to treat cancer to overcome drug toxicity and resistance with natural compounds. We assessed the effects of indicaxanthin (Ind), a pigment obtained from Opuntia ficus-indica (L. Mill) fruit, combined with cisplatin (CDDP) against cervical cancer [...] Read more.
Combining phytochemicals with chemotherapics is an emerging strategy to treat cancer to overcome drug toxicity and resistance with natural compounds. We assessed the effects of indicaxanthin (Ind), a pigment obtained from Opuntia ficus-indica (L. Mill) fruit, combined with cisplatin (CDDP) against cervical cancer cells (HeLa). Measured cell viability via Trypan blue assay; cell morphology via fluorescence microscopy; apoptosis, cell cycle, mitochondrial membrane potential (MMP) and cell redox balance via flow-cytometry; expression levels of apoptosis-related proteins via western blot. Cell viability assays and Chou-Talalay plot demonstrated that the combination of CDDP and Ind had synergistic cytotoxic effects. Combined treatment had significant effects (p < 0.05) on phosphatidylserine externalization, cell morphological changes, cell cycle arrest, fall in MMP, ROS production and GSH decay compared with the individual treatment groups. Bax, cytochrome c, p53 and p21waf1 were over-expressed, while Bcl-2 was downregulated. Pre-treatment with N-acetyl-l-cysteine abolished the observed synergistic effects. We also demonstrated potentiation of CDDP anticancer activity by nutritionally relevant concentrations of Ind. Oxidative stress-dependent mitochondrial cell death is the basis of the chemosensitizing effect of Ind combined with CDDP against HeLa cancer cells. ROS act as upstream signaling molecules to initiate apoptosis via p53/p21waf1 axis. Ind can be a phytochemical of interest in combo-therapy. Full article
(This article belongs to the Special Issue Biomolecules and Cancer Prevention)
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Open AccessReview
Effects of NAD+ in Caenorhabditis elegans Models of Neuronal Damage
Biomolecules 2020, 10(7), 993; https://doi.org/10.3390/biom10070993 (registering DOI) - 02 Jul 2020
Viewed by 174
Abstract
Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor that mediates numerous biological processes in all living cells. Multiple NAD+ biosynthetic enzymes and NAD+-consuming enzymes are involved in neuroprotection and axon regeneration. The nematode Caenorhabditis elegans has served as [...] Read more.
Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor that mediates numerous biological processes in all living cells. Multiple NAD+ biosynthetic enzymes and NAD+-consuming enzymes are involved in neuroprotection and axon regeneration. The nematode Caenorhabditis elegans has served as a model to study the neuronal role of NAD+ because many molecular components regulating NAD+ are highly conserved. This review focuses on recent findings using C. elegans models of neuronal damage pertaining to the neuronal functions of NAD+ and its precursors, including a neuroprotective role against excitotoxicity and axon degeneration as well as an inhibitory role in axon regeneration. The regulation of NAD+ levels could be a promising therapeutic strategy to counter many neurodegenerative diseases, as well as neurotoxin-induced and traumatic neuronal damage. Full article
(This article belongs to the Special Issue Nicotinamide in Health and Diseases)
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Open AccessArticle
Implication of Opioid Receptors in the Antihypertensive Effect of a Novel Chicken Foot-Derived Peptide
Biomolecules 2020, 10(7), 992; https://doi.org/10.3390/biom10070992 - 02 Jul 2020
Viewed by 141
Abstract
The peptide AVFQHNCQE demonstrated to produce nitric oxide-mediated antihypertensive effect. This study investigates the bioavailability and the opioid-like activity of this peptide after its oral administration. For this purpose, in silico and in vitro approaches were used to study the peptide susceptibility to [...] Read more.
The peptide AVFQHNCQE demonstrated to produce nitric oxide-mediated antihypertensive effect. This study investigates the bioavailability and the opioid-like activity of this peptide after its oral administration. For this purpose, in silico and in vitro approaches were used to study the peptide susceptibility to GI digestion. In addition, AVFQHNCQE absorption was studied both in vitro by using Caco-2 cell monolayers and in vivo evaluating peptide presence in plasma from Wistar rats by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and by ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Both in vivo and in vitro experiments demonstrated that peptide AVFQHNCQE was not absorbed. Thus, the potential involvement of opioid receptors in the BP-lowering effect of AVFQHNCQE was studied in the presence of opioid receptors-antagonist Naloxone. No changes in blood pressure were recorded in rats administered Naloxone, demonstrating that AVFQHNCQE antihypertensive effect is mediated through its interaction with opioid receptors. AVFQHNCQE opioid-like activity would clarify the antihypertensive properties of AVFQHNCQE despite its lack of absorption. Full article
(This article belongs to the Special Issue Metabolomics and Integrated Multi-Omics in Health and Disease)
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Open AccessReview
A Short Review on the Valorization of Green Seaweeds and Ulvan: FEEDSTOCK for Chemicals and Biomaterials
Biomolecules 2020, 10(7), 991; https://doi.org/10.3390/biom10070991 - 02 Jul 2020
Viewed by 179
Abstract
This short review analyzed the recent trend towards, progresses towards the preparation of chemicals of, and value-added biomaterials from marine macroalgae resources, especially green seaweeds and their derived ulvan polysaccharides for various applications. In recent years, ulvan both in pristine and modified forms [...] Read more.
This short review analyzed the recent trend towards, progresses towards the preparation of chemicals of, and value-added biomaterials from marine macroalgae resources, especially green seaweeds and their derived ulvan polysaccharides for various applications. In recent years, ulvan both in pristine and modified forms has gained a large amount of attention for its effective utilization in various areas due to its unique physiochemical properties, lack of exploration, and higher green seaweed production. The pristine form of ulvan (sulfated polysaccharides) is used as a bio-component; food ingredient; or a raw material for the production of numerous chemicals such as fuels, cosmetics, and pharmaceuticals, whereas its modified form is used in the sector of composites, membranes, and scaffolds, among others, because of its physicochemical properties. This review highlights the utilization of green seaweed and its derived ulvan polysaccharides for the preparation of numerous chemicals (e.g., solvents, fuel, and gas) and also value-added biomaterials with various morphologies (e.g., gels, fibers, films, scaffolds, nanomaterials, and composites). Full article
(This article belongs to the Section Biological Materials)
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Open AccessArticle
Interaction between Mesocortical and Mesothalamic Catecholaminergic Transmissions Associated with NMDA Receptor in the Locus Coeruleus
Biomolecules 2020, 10(7), 990; https://doi.org/10.3390/biom10070990 - 01 Jul 2020
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Abstract
Noncompetitive N-methyl-D-aspartate/glutamate receptor (NMDAR) antagonists contribute to the pathophysiology of schizophrenia and mood disorders but improve monoaminergic antidepressant-resistant mood disorder and suicidal ideation. The mechanisms of the double-edged sword clinical action of NMDAR antagonists remained to be clarified. The present study determined the [...] Read more.
Noncompetitive N-methyl-D-aspartate/glutamate receptor (NMDAR) antagonists contribute to the pathophysiology of schizophrenia and mood disorders but improve monoaminergic antidepressant-resistant mood disorder and suicidal ideation. The mechanisms of the double-edged sword clinical action of NMDAR antagonists remained to be clarified. The present study determined the interaction between the NMDAR antagonist (MK801), α1 adrenoceptor antagonist (prazosin), and α2A adrenoceptor agonist (guanfacine) on mesocortical and mesothalamic catecholaminergic transmission, and thalamocortical glutamatergic transmission using multiprobe microdialysis. The inhibition of NMDAR in the locus coeruleus (LC) by local MK801 administration enhanced both the mesocortical noradrenergic and catecholaminergic coreleasing (norepinephrine and dopamine) transmissions. The mesothalamic noradrenergic transmission was also enhanced by local MK801 administration in the LC. These mesocortical and mesothalamic transmissions were activated by intra-LC disinhibition of transmission of γ-aminobutyric acid (GABA) via NMDAR inhibition. Contrastingly, activated mesothalamic noradrenergic transmission by MK801 enhanced intrathalamic GABAergic inhibition via the α1 adrenoceptor, resulting in the suppression of thalamocortical glutamatergic transmission. The thalamocortical glutamatergic terminal stimulated the presynaptically mesocortical catecholaminergic coreleasing terminal in the superficial cortical layers, but did not have contact with the mesocortical selective noradrenergic terminal (which projected terminals to deeper cortical layers). Furthermore, the α2A adrenoceptor suppressed the mesocortical and mesothalamic noradrenergic transmissions somatodendritically in the LC and presynaptically/somatodendritically in the reticular thalamic nucleus (RTN). These discrepancies between the noradrenergic and catecholaminergic transmissions in the mesocortical and mesothalamic pathways probably constitute the double-edged sword clinical action of noncompetitive NMDAR antagonists. Full article
(This article belongs to the Special Issue NMDA Receptor in Health and Diseases)
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Open AccessReview
Cell-Adhesion Properties of β-Subunits in the Regulation of Cardiomyocyte Sodium Channels
Biomolecules 2020, 10(7), 989; https://doi.org/10.3390/biom10070989 - 01 Jul 2020
Viewed by 222
Abstract
Voltage-gated sodium (Nav) channels drive the rising phase of the action potential, essential for electrical signalling in nerves and muscles. The Nav channel α-subunit contains the ion-selective pore. In the cardiomyocyte, Nav1.5 is the main Nav channel α-subunit isoform, with a smaller expression [...] Read more.
Voltage-gated sodium (Nav) channels drive the rising phase of the action potential, essential for electrical signalling in nerves and muscles. The Nav channel α-subunit contains the ion-selective pore. In the cardiomyocyte, Nav1.5 is the main Nav channel α-subunit isoform, with a smaller expression of neuronal Nav channels. Four distinct regulatory β-subunits (β1–4) bind to the Nav channel α-subunits. Previous work has emphasised the β-subunits as direct Nav channel gating modulators. However, there is now increasing appreciation of additional roles played by these subunits. In this review, we focus on β-subunits as homophilic and heterophilic cell-adhesion molecules and the implications for cardiomyocyte function. Based on recent cryogenic electron microscopy (cryo-EM) data, we suggest that the β-subunits interact with Nav1.5 in a different way from their binding to other Nav channel isoforms. We believe this feature may facilitate trans-cell-adhesion between β1-associated Nav1.5 subunits on the intercalated disc and promote ephaptic conduction between cardiomyocytes. Full article
Open AccessReview
Bioactive Natural Compounds and Antioxidant Activity of Essential Oils from Spice Plants: New Findings and Potential Applications
Biomolecules 2020, 10(7), 988; https://doi.org/10.3390/biom10070988 - 01 Jul 2020
Viewed by 206
Abstract
Spice plants have a great influence on world history. For centuries, different civilizations have used them to condiment the foods of kings and nobles and applied them as embalming preservatives, perfumes, cosmetics, and medicines in different regions of the world. In general, these [...] Read more.
Spice plants have a great influence on world history. For centuries, different civilizations have used them to condiment the foods of kings and nobles and applied them as embalming preservatives, perfumes, cosmetics, and medicines in different regions of the world. In general, these plants have formed the basis of traditional medicine and some of their derived substances have been utilized to treat different human diseases. Essential oils (EOs) obtained from these plants have been also used as therapeutic agents and have shown supportive uses in remedial practices. The discovery and development of bioactive compounds from these natural products, based on their traditional uses, play an important role in developing the scientific evidence of their potential pharmaceutical, cosmetic, and food applications. In the present review, using recent studies, we exhibit a general overview of the main aspects related to the importance of spice plants widely used in traditional medicine: Cinnamomum zeylanicum (true cinnamon), Mentha piperita (peppermint), Ocimum basilicum (basil), Origanum vulgare (oregano), Piper nigrum (black pepper), Rosmarinus officinalis (rosemary), and Thymus vulgaris (thyme); and we discuss new findings of the bioactive compounds obtained from their EOs, their potential applications, as well as their molecular mechanisms of action, focusing on their antioxidant activity. We also exhibit the main in vitro methods applied to determine the antioxidant activities of these natural products. Full article
(This article belongs to the Special Issue Perspectives of Essential Oils)
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Open AccessReview
The Alcohol–High-Density Lipoprotein Athero-Protective Axis
Biomolecules 2020, 10(7), 987; https://doi.org/10.3390/biom10070987 - 01 Jul 2020
Viewed by 148
Abstract
Ingestion of alcohol is associated with numerous changes in human energy metabolism, especially that of plasma lipids and lipoproteins. Regular moderate alcohol consumption is associated with reduced atherosclerotic cardiovascular disease (ASCVD), an effect that has been attributed to the concurrent elevations of plasma [...] Read more.
Ingestion of alcohol is associated with numerous changes in human energy metabolism, especially that of plasma lipids and lipoproteins. Regular moderate alcohol consumption is associated with reduced atherosclerotic cardiovascular disease (ASCVD), an effect that has been attributed to the concurrent elevations of plasma high-density lipoprotein-cholesterol (HDL-C) concentrations. More recent evidence has accrued against the hypothesis that raising plasma HDL concentrations prevents ASCVD so that other metabolic processes associated with alcohol consumption have been considered. This review explored the roles of other metabolites induced by alcohol consumption—triglyceride-rich lipoproteins, non-esterified free fatty acids, and acetate, the terminal alcohol metabolite in athero-protection: Current evidence suggests that acetate has a key role in athero-protection but additional studies are needed. Full article
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Open AccessCommunication
Hapten Design and Monoclonal Antibody to Fluoroacetamide, a Small and Highly Toxic Chemical
Biomolecules 2020, 10(7), 986; https://doi.org/10.3390/biom10070986 - 01 Jul 2020
Viewed by 173
Abstract
Fluoroacetamide (FAM) is a small (77 Da) and highly toxic chemical, formerly used as a rodenticide and potentially as a poison by terrorists. Poisoning with FAM has occurred in humans, but few reliably rapid detection methods and antidotes have been reported. Therefore, producing [...] Read more.
Fluoroacetamide (FAM) is a small (77 Da) and highly toxic chemical, formerly used as a rodenticide and potentially as a poison by terrorists. Poisoning with FAM has occurred in humans, but few reliably rapid detection methods and antidotes have been reported. Therefore, producing a specific antibody to FAM is not only critical for the development of a fast diagnostic but also a potential treatment. However, achieving this goal is a great challenge, mainly due to the very low molecular weight of FAM. Here, we design two groups of FAM haptens for the first time, maximally exposing the fluorine or amino groups, with the aid of linear aliphatic or phenyl-contained spacer arms. Interestingly, whereas the hapten with fluorine at the far end of the hapten did not induce an antibody response to FAM, the hapten with an amino group at the far end and phenyl-contained spacer arm triggered a significantly specific antibody response. Finally, a monoclonal antibody (mAb) named 5D11 was successfully obtained with an IC50 value of 97 μg mL−1 and negligible cross-reactivities to the other nine functional and structural analogs. Full article
(This article belongs to the Section Biomacromolecules)
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Open AccessReview
Post-Developmental Roles of Notch Signaling in the Nervous System
Biomolecules 2020, 10(7), 985; https://doi.org/10.3390/biom10070985 - 01 Jul 2020
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Abstract
Since its discovery in Drosophila, the Notch signaling pathway has been studied in numerous developmental contexts in diverse multicellular organisms. The role of Notch signaling in nervous system development has been extensively investigated by numerous scientists, partially because many of the core [...] Read more.
Since its discovery in Drosophila, the Notch signaling pathway has been studied in numerous developmental contexts in diverse multicellular organisms. The role of Notch signaling in nervous system development has been extensively investigated by numerous scientists, partially because many of the core Notch signaling components were initially identified through their dramatic ‘neurogenic’ phenotype of developing fruit fly embryos. Components of the Notch signaling pathway continue to be expressed in mature neurons and glia cells, which is suggestive of a role in the post-developmental nervous system. The Notch pathway has been, so far, implicated in learning and memory, social behavior, addiction, and other complex behaviors using genetic model organisms including Drosophila and mice. Additionally, Notch signaling has been shown to play a modulatory role in several neurodegenerative disease model animals and in mediating neural toxicity of several environmental factors. In this paper, we summarize the knowledge pertaining to the post-developmental roles of Notch signaling in the nervous system with a focus on discoveries made using the fruit fly as a model system as well as relevant studies in C elegans, mouse, rat, and cellular models. Since components of this pathway have been implicated in the pathogenesis of numerous psychiatric and neurodegenerative disorders in human, understanding the role of Notch signaling in the mature brain using model organisms will likely provide novel insights into the mechanisms underlying these diseases. Full article
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Open AccessArticle
Deep Neural Networks for Dental Implant System Classification
Biomolecules 2020, 10(7), 984; https://doi.org/10.3390/biom10070984 - 01 Jul 2020
Viewed by 169
Abstract
In this study, we used panoramic X-ray images to classify and clarify the accuracy of different dental implant brands via deep convolutional neural networks (CNNs) with transfer-learning strategies. For objective labeling, 8859 implant images of 11 implant systems were used from digital panoramic [...] Read more.
In this study, we used panoramic X-ray images to classify and clarify the accuracy of different dental implant brands via deep convolutional neural networks (CNNs) with transfer-learning strategies. For objective labeling, 8859 implant images of 11 implant systems were used from digital panoramic radiographs obtained from patients who underwent dental implant treatment at Kagawa Prefectural Central Hospital, Japan, between 2005 and 2019. Five deep CNN models (specifically, a basic CNN with three convolutional layers, VGG16 and VGG19 transfer-learning models, and finely tuned VGG16 and VGG19) were evaluated for implant classification. Among the five models, the finely tuned VGG16 model exhibited the highest implant classification performance. The finely tuned VGG19 was second best, followed by the normal transfer-learning VGG16. We confirmed that the finely tuned VGG16 and VGG19 CNNs could accurately classify dental implant systems from 11 types of panoramic X-ray images. Full article
(This article belongs to the Special Issue Application of Artificial Intelligence for Medical Research)
Open AccessArticle
Unveiling the Mechanism of Action of 7α-acetoxy-6β-hydroxyroyleanone on an MRSA/VISA Strain: Membrane and Cell Wall Interactions
Biomolecules 2020, 10(7), 983; https://doi.org/10.3390/biom10070983 - 30 Jun 2020
Viewed by 277
Abstract
The number of cases of failure in the treatment of infections associated with resistant bacteria is on the rise, due to the decreasing efficacy of current antibiotics. Notably, 7α-Acetoxy-6β-hydroxyroyleanone (AHR), a diterpene isolated from different Plectranthus species, showed antibacterial activity, namely against Methicillin-resistant [...] Read more.
The number of cases of failure in the treatment of infections associated with resistant bacteria is on the rise, due to the decreasing efficacy of current antibiotics. Notably, 7α-Acetoxy-6β-hydroxyroyleanone (AHR), a diterpene isolated from different Plectranthus species, showed antibacterial activity, namely against Methicillin-resistant Staphylococcus aureus (MRSA) strains. The high antibacterial activity and low cytotoxicity render this natural compound an interesting alternative against resistant bacteria. The aim of this study is to understand the mechanism of action of AHR on MRSA, using the MRSA/Vancomycin-intermediate S. aureus (VISA) strain CIP 106760, and to study the AHR effect on lipid bilayers and on the cell wall. Although AHR interacted with lipid bilayers, it did not have a significant effect on membrane passive permeability. Alternatively, bacteria treated with this royleanone displayed cell wall disruption, without revealing cell lysis. In conclusion, the results gathered so far point to a yet undescribed mode of action that needs further investigation. Full article
(This article belongs to the Special Issue Selected Papers from Bio.Natural Meeting 2019)
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Open AccessArticle
Tumoricidal and Bactericidal Properties of ZnONPs Synthesized Using Cassia auriculata Leaf Extract
Biomolecules 2020, 10(7), 982; https://doi.org/10.3390/biom10070982 - 30 Jun 2020
Viewed by 161
Abstract
In this work, we aimed to synthesize zinc oxide nanoparticles (ZnONPs) using an aqueous extract of Cassia auriculata leaves (CAE) at room temperature without the provision of additional surfactants or capping agents. The formation of as-obtained ZnONPs was analyzed by UV–visible (ultraviolet) absorption [...] Read more.
In this work, we aimed to synthesize zinc oxide nanoparticles (ZnONPs) using an aqueous extract of Cassia auriculata leaves (CAE) at room temperature without the provision of additional surfactants or capping agents. The formation of as-obtained ZnONPs was analyzed by UV–visible (ultraviolet) absorption and emission spectroscopy, X-ray photoemission spectroscopy (XPS), X-ray diffraction analysis (XRD), energy dispersive X-ray diffraction (EDX), thermogravimetric analysis/differential thermal analysis (TGA-DTA), scanning electron microscopy (SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), and selected area electron diffraction (SAED). The XRD results reflect the wurtzite structure of as-prepared ZnONPs, which produced diffraction patterns showing hexagonal phases. The SEM images indicate that the morphology of as-prepared ZnONPs is composed of hexagonal nanostructures with an average diameter of 20 nm. The HR-TEM result shows that the inter-planar distance between two lattice fringes is 0.260 nm, which coincides with the distance between the adjacent (d-spacing) of the (002) lattice plane of ZnO. The fluorescence emission spectrum of ZnONPs dispersed in ethanol shows an emission maximum at 569 nm, revealing the semiconductor nature of ZnO. As-obtained ZnONPs enhanced the tumoricidal property of CAE in MCF-7 breast cancer cells without significant inhibition of normal human breast cells, MCF-12A. Furthermore, we have studied the antibacterial effects of ZnONPs, which showed direct cell surface contact, resulting in the disturbance of bacterial cell integrity. Full article
Open AccessArticle
Prediction Value of Serum NGAL in the Diagnosis and Prognosis of Experimental Acute and Chronic Kidney Injuries
Biomolecules 2020, 10(7), 981; https://doi.org/10.3390/biom10070981 - 30 Jun 2020
Viewed by 166
Abstract
Sensitive and accurate serum biomarkers for monitoring acute and chronic kidney disease progression are more convenient and can better evaluate drug efficiency in pharmacological research. Neutrophil Gelatinase-associated Lipocalin (NGAL) is considered a hopeful early biomarker of acute kidney injury (AKI), but its utility [...] Read more.
Sensitive and accurate serum biomarkers for monitoring acute and chronic kidney disease progression are more convenient and can better evaluate drug efficiency in pharmacological research. Neutrophil Gelatinase-associated Lipocalin (NGAL) is considered a hopeful early biomarker of acute kidney injury (AKI), but its utility in early prediction and prognosis of diabetic nephropathy (DN) and immune-mediated glomerulonephritis is still not clear. Moreover, detailed prognosis studies of NGAL in AKI are lacking, and most studies use a urine source. In the current study, through two experimental AKI and two chronic kidney injury animal models, serum NGAL (sNGAL) prediction values on diagnosis and prognosis of kidney injuries in animal disease models have been investigated thoroughly. Four experimental kidney disease models include cisplatin-induced and lipopolysaccharide (LPS)-induced AKI, streptozocin-induced diabetic nephropathy (DN), and cationized-bovine serum albumin (c-BSA)-induced membranous nephropathy (MN), respectively. The sNGAL concentration was measured at different stages of kidney injury (KI) in each experimental model, and receiver operating characteristic (ROC) analyses were performed to investigate the diagnosis efficiency of sNGAL for KI. Western blot and immunohistochemistry were used to measure the protein levels in the kidneys, and pathological analysis was used as the gold standard to confirm KI. Results suggest that sNGAL can predict early diagnosis of cisplatin-induced AKI accurately but is less powerful in later stages compared to blood urea nitrogen (BUN) and serum creatinine (Scr). sNGAL is sensitive but lacks specificity to evaluate early kidney injury for LPS-induced AKI under low-dosage LPS challenge. sNGAL is not an efficient biomarker for early diagnosis of STZ-induced DN, but sNGAL is an efficient predictor for the early diagnosis and prognosis of immune-mediated MN. In conclusion, application of sNGAL as a kidney injury biomarker to determine the diagnosis and prognosis in pharmacological studies is dependent on experimental animal models. Full article
(This article belongs to the Section Molecular Biology)
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Open AccessReview
Natural Ergot Alkaloids in Ocular Pharmacotherapy: Known Molecules for Novel Nanoparticle-Based Delivery Systems
Biomolecules 2020, 10(7), 980; https://doi.org/10.3390/biom10070980 - 30 Jun 2020
Viewed by 189
Abstract
Several pharmacological properties are attributed to ergot alkaloids as a result of their antibacterial, antiproliferative, and antioxidant effects. Although known for their biomedical applications (e.g., for the treatment of glaucoma), most ergot alkaloids exhibit high toxicological risk and may even be lethal to [...] Read more.
Several pharmacological properties are attributed to ergot alkaloids as a result of their antibacterial, antiproliferative, and antioxidant effects. Although known for their biomedical applications (e.g., for the treatment of glaucoma), most ergot alkaloids exhibit high toxicological risk and may even be lethal to humans and animals. Their pharmacological profile results from the structural similarity between lysergic acid-derived compounds and noradrenalin, dopamine, and serotonin neurotransmitters. To reduce their toxicological risk, while increasing their bioavailability, improved delivery systems were proposed. This review discusses the safety aspects of using ergot alkaloids in ocular pharmacology and proposes the development of lipid and polymeric nanoparticles for the topical administration of these drugs to enhance their therapeutic efficacy for the treatment of glaucoma. Full article
(This article belongs to the Special Issue Pharmacology of Medicinal Plants)
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Open AccessReview
Mechanisms of Resistance to Immunotoxins Containing Pseudomonas Exotoxin A in Cancer Therapy
Biomolecules 2020, 10(7), 979; https://doi.org/10.3390/biom10070979 - 30 Jun 2020
Viewed by 176
Abstract
Immunotoxins are a class of targeted cancer therapeutics in which a toxin such as Pseudomonas exotoxin A (PE) is linked to an antibody or cytokine to direct the toxin to a target on cancer cells. While a variety of PE-based immunotoxins have been [...] Read more.
Immunotoxins are a class of targeted cancer therapeutics in which a toxin such as Pseudomonas exotoxin A (PE) is linked to an antibody or cytokine to direct the toxin to a target on cancer cells. While a variety of PE-based immunotoxins have been developed and a few have demonstrated promising clinical and preclinical results, cancer cells frequently have or develop resistance to these immunotoxins. This review presents our current understanding of the mechanism of action of PE-based immunotoxins and discusses cellular mechanisms of resistance that interfere with various steps of the pathway. These steps include binding of the immunotoxin to the target antigen, internalization, intracellular processing and trafficking to reach the cytosol, inhibition of protein synthesis through ADP-ribosylation of elongation factor 2 (EF2), and induction of apoptosis. Combination therapies that increase immunotoxin action and overcome specific mechanisms of resistance are also reviewed. Full article
(This article belongs to the Special Issue Immunotoxins: From Design to Clinical Application)
Open AccessArticle
An Economic Dilemma Between Molecular Weapon Systems May Explain an Arachno-atypical Venom in Wasp Spiders (Argiope bruennichi)
Biomolecules 2020, 10(7), 978; https://doi.org/10.3390/biom10070978 - 30 Jun 2020
Viewed by 335
Abstract
Spiders use venom to subdue their prey, but little is known about the diversity of venoms in different spider families. Given the limited data available for orb-weaver spiders (Araneidae), we selected the wasp spider Argiope bruennichi for detailed analysis. Our strategy combined a [...] Read more.
Spiders use venom to subdue their prey, but little is known about the diversity of venoms in different spider families. Given the limited data available for orb-weaver spiders (Araneidae), we selected the wasp spider Argiope bruennichi for detailed analysis. Our strategy combined a transcriptomics pipeline based on multiple assemblies with a dual proteomics workflow involving parallel mass spectrometry techniques and electrophoretic profiling. We found that the remarkably simple venom of A. bruennichi has an atypical composition compared to other spider venoms, prominently featuring members of the cysteine-rich secretory protein, antigen 5 and pathogenesis-related protein 1 (CAP) superfamily and other, mostly high-molecular-weight proteins. We also detected a subset of potentially novel toxins similar to neuropeptides. We discuss the potential function of these proteins in the context of the unique hunting behavior of wasp spiders, which rely mostly on silk to trap their prey. We propose that the simplicity of the venom evolved to solve an economic dilemma between two competing yet metabolically expensive weapon systems. This study emphasizes the importance of cutting-edge methods to encompass the lineages of smaller venomous species that have yet to be characterized in detail, allowing us to understand the biology of their venom systems and to mine this prolific resource for translational research. Full article
(This article belongs to the Section Bioinformatics and Systems Biology)
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Open AccessArticle
Survey and Validation of tRNA Modifications and Their Corresponding Genes in Bacillus subtilis sp Subtilis Strain 168
Biomolecules 2020, 10(7), 977; https://doi.org/10.3390/biom10070977 - 30 Jun 2020
Viewed by 245
Abstract
Extensive knowledge of both the nature and position of tRNA modifications in all cellular tRNAs has been limited to two bacteria, Escherichia coli and Mycoplasma capricolum. Bacillus subtilis sp subtilis strain 168 is the model Gram-positive bacteria and the list of the [...] Read more.
Extensive knowledge of both the nature and position of tRNA modifications in all cellular tRNAs has been limited to two bacteria, Escherichia coli and Mycoplasma capricolum. Bacillus subtilis sp subtilis strain 168 is the model Gram-positive bacteria and the list of the genes involved in tRNA modifications in this organism is far from complete. Mass spectrometry analysis of bulk tRNA extracted from B. subtilis, combined with next generation sequencing technologies and comparative genomic analyses, led to the identification of 41 tRNA modification genes with associated confidence scores. Many differences were found in this model Gram-positive bacteria when compared to E. coli. In general, B. subtilis tRNAs are less modified than those in E. coli, even if some modifications, such as m1A22 or ms2t6A, are only found in the model Gram-positive bacteria. Many examples of non-orthologous displacements and of variations in the most complex pathways are described. Paralog issues make uncertain direct annotation transfer from E. coli to B. subtilis based on homology only without further experimental validation. This difficulty was shown with the identification of the B. subtilis enzyme that introduces ψ at positions 31/32 of the tRNAs. This work presents the most up to date list of tRNA modification genes in B. subtilis, identifies the gaps in knowledge, and lays the foundation for further work to decipher the physiological role of tRNA modifications in this important model organism and other bacteria. Full article
(This article belongs to the Section Biomacromolecules)
Open AccessReview
Bioactive Compounds from Hermetia Illucens Larvae as Natural Ingredients for Cosmetic Application
Biomolecules 2020, 10(7), 976; https://doi.org/10.3390/biom10070976 - 29 Jun 2020
Viewed by 248
Abstract
Due to the sustainable organic matter bioconversion process used as substrate for its development, the Hermetia illucens (Linnaeus) larvae biomass is considered a source of compounds with high aggregate value and quite a promising market. The materials that can be extracted from H. [...] Read more.
Due to the sustainable organic matter bioconversion process used as substrate for its development, the Hermetia illucens (Linnaeus) larvae biomass is considered a source of compounds with high aggregate value and quite a promising market. The materials that can be extracted from H. illucens larvae have opened the door to a diverse new field of ingredients, mainly for the feed and food industry, but also with potential applicability in cosmetics. In this review we succinctly describe the larval development and rearing cycle, the main compounds identified from different types of extractions, their bioactivities and focus on possible applications in cosmetic products. A search was made in the databases PubMed, ScienceDirect and Web of Science with the terms ‘Hermetia illucens’, ‘bioactives’, ‘biochemical composition’ and ‘cosmetics ingredients’, which included 71 articles published since 1994. Full article
(This article belongs to the Special Issue Selected Papers from Bio.Natural Meeting 2019)
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Open AccessArticle
Reduced Reelin Expression in the Hippocampus after Traumatic Brain Injury
Biomolecules 2020, 10(7), 975; https://doi.org/10.3390/biom10070975 - 29 Jun 2020
Viewed by 219
Abstract
Traumatic brain injury (TBI) is a relatively common occurrence following accidents or violence, and often results in long-term cognitive or motor disability. Despite the high health cost associated with this type of injury, presently there are no effective treatments for many neurological symptoms [...] Read more.
Traumatic brain injury (TBI) is a relatively common occurrence following accidents or violence, and often results in long-term cognitive or motor disability. Despite the high health cost associated with this type of injury, presently there are no effective treatments for many neurological symptoms resulting from TBI. This is due in part to our limited understanding of the mechanisms underlying brain dysfunction after injury. In this study, we used the mouse controlled cortical impact (CCI) model to investigate the effects of TBI, and focused on Reelin, an extracellular protein that critically regulates brain development and modulates synaptic activity in the adult brain. We found that Reelin expression decreases in forebrain regions after TBI, and that the number of Reelin-expressing cells decrease specifically in the hippocampus, an area of the brain that plays an important role in learning and memory. We also conducted in vitro experiments using mouse neuronal cultures and discovered that Reelin protects hippocampal neuronal cells from glutamate-induced neurotoxicity, a well-known secondary effect of TBI. Together our findings suggest that the loss of Reelin expression may contribute to neuronal death in the hippocampus after TBI, and raise the possibility that increasing Reelin levels or signaling activity may promote functional recovery. Full article
(This article belongs to the Special Issue Reelin, a Hub Protein during Nervous System Development?)
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Open AccessArticle
Transcriptome Based Profiling of the Immune Cell Gene Signature in Rat Experimental Colitis and Human IBD Tissue Samples
Biomolecules 2020, 10(7), 974; https://doi.org/10.3390/biom10070974 - 29 Jun 2020
Viewed by 215
Abstract
Chronic intestinal inflammation is characteristic of Inflammatory Bowel Disease (IBD) that is associated with the exaggerated infiltration of immune cells. A complex interplay of inflammatory mediators and different cell types in the colon are responsible for the maintenance of tissue homeostasis and affect [...] Read more.
Chronic intestinal inflammation is characteristic of Inflammatory Bowel Disease (IBD) that is associated with the exaggerated infiltration of immune cells. A complex interplay of inflammatory mediators and different cell types in the colon are responsible for the maintenance of tissue homeostasis and affect pathological conditions. Gene expression alteration of colon biopsies from IBD patients and an in vivo rat model of colitis were examined by RNA-Seq and QPCR, while we used in silico methods, such as Ingenuity Pathway Analysis (IPA) application and the Immune Gene Signature (ImSig) package of R, to interpret whole transcriptome data and estimate immune cell composition of colon tissues. Transcriptome profiling of in vivo colitis model revealed the most significant activation of signaling pathways responsible for leukocyte recruitment and diapedesis. We observed significant alteration of genes related to glycosylation or sensing of danger signals and pro- and anti-inflammatory cytokines and chemokines, as well as adhesion molecules. We observed the elevated expression of genes that implies the accumulation of monocytes, macrophages, neutrophils and B cells in the inflamed colon tissue. In contrast, the rate of T-cells slightly decreased in the inflamed regions. Interestingly, natural killer and plasma cells do not show enrichment upon colon inflammation. In general, whole transcriptome analysis of the in vivo experimental model of colitis with subsequent bioinformatics analysis provided a better understanding of the dynamic changes in the colon tissue of IBD patients. Full article
(This article belongs to the Section Molecular Biology)
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Open AccessReview
Mesothelin-Targeted Recombinant Immunotoxins for Solid Tumors
Biomolecules 2020, 10(7), 973; https://doi.org/10.3390/biom10070973 - 28 Jun 2020
Viewed by 232
Abstract
Mesothelin (MSLN) is a cell surface glycoprotein normally expressed only on serosal surfaces, and not found in the parenchyma of vital organs. Many solid tumors also express MSLN, including mesothelioma and pancreatic adenocarcinoma. Due to this favorable expression profile, MSLN represents a viable [...] Read more.
Mesothelin (MSLN) is a cell surface glycoprotein normally expressed only on serosal surfaces, and not found in the parenchyma of vital organs. Many solid tumors also express MSLN, including mesothelioma and pancreatic adenocarcinoma. Due to this favorable expression profile, MSLN represents a viable target for directed anti-neoplastic therapies, such as recombinant immunotoxins (iToxs). Pre-clinical testing of MSLN-targeted iTox’s has yielded a strong body of evidence for activity against a number of solid tumors. This has led to multiple clinical trials, testing the safety and efficacy of the clinical leads SS1P and LMB-100. While promising clinical results have been observed, neutralizing anti-drug antibody (ADA) formation presents a major challenge to overcome in the therapeutic development process. Additionally, on-target, off-tumor toxicity from serositis and non-specific capillary leak syndrome (CLS) also limits the dose, and therefore, impact anti-tumor activity. This review summarizes existing pre-clinical and clinical data on MSLN-targeted iTox’s. In addition, we address the potential future directions of research to enhance the activity of these anti-tumor agents. Full article
(This article belongs to the Special Issue Immunotoxins: From Design to Clinical Application)
Open AccessArticle
Evaluation of Resin-Based Material Containing Copaiba Oleoresin (Copaifera Reticulata Ducke): Biological Effects on the Human Dental Pulp Stem Cells
Biomolecules 2020, 10(7), 972; https://doi.org/10.3390/biom10070972 (registering DOI) - 28 Jun 2020
Viewed by 181
Abstract
The purpose of this study was to analyze in vitro the biological effects on human dental pulp stem cells triggered in response to substances leached or dissolved from two experimental cements for dental pulp capping. The experimental materials, based on extracts from Copaifera [...] Read more.
The purpose of this study was to analyze in vitro the biological effects on human dental pulp stem cells triggered in response to substances leached or dissolved from two experimental cements for dental pulp capping. The experimental materials, based on extracts from Copaifera reticulata Ducke (COP), were compared to calcium hydroxide [Ca(OH)2] and mineral trioxide aggregate (MTA), materials commonly used for direct dental pulp capping in restorative dentistry. For this, human dental pulp stem cells were exposed to COP associated or not with Ca(OH)2 or MTA. Cell cytocompatibility, migration, and differentiation (mineralized nodule formation (Alizarin red assay) and gene expression (RT-qPCR) of OCN, DSPP, and HSP-27 (genes regulated in biomineralization events)) were evaluated. The results showed that the association of COP reduced the cytotoxicity of Ca(OH)2. Upregulations of the OCN, DSPP, and HSP-27 genes were observed in response to the association of COP to MTA, and the DSPP and HSP-27 genes were upregulated in the Ca(OH)2 + COP group. In up to 24 h, cell migration was significantly enhanced in the MTA + COP and Ca(OH)2 + COP groups. In conclusion, the combination of COP with the currently used materials for dental pulp capping [Ca(OH)2 and MTA] improved the cell activities related to pulp repair (i.e., cytocompatibility, differentiation, mineralization, and migration) including a protective effect against the cytotoxicity of Ca(OH)2. Full article
(This article belongs to the Special Issue Application and Mechanism of Natural Compounds in Dentistry)
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Open AccessArticle
Validation of a Novel Zebrafish Model of Dengue Virus (DENV-3) Pathology Using the Pentaherbal Medicine Denguenil Vati
Biomolecules 2020, 10(7), 971; https://doi.org/10.3390/biom10070971 - 28 Jun 2020
Viewed by 4126
Abstract
Dengue is a devastating viral fever of humans, caused by dengue virus. Using a novel zebrafish model of dengue pathology, we validated the potential anti-dengue therapeutic properties of pentaherbal medicine, Denguenil Vati. At two different time points (at 7 and 14 days post [...] Read more.
Dengue is a devastating viral fever of humans, caused by dengue virus. Using a novel zebrafish model of dengue pathology, we validated the potential anti-dengue therapeutic properties of pentaherbal medicine, Denguenil Vati. At two different time points (at 7 and 14 days post infection with dengue virus), we tested three translational doses (5.8 μg/kg, 28 μg/kg, and 140 μg/kg). Dose- and time-dependent inhibition of the viral copy numbers was identified upon Denguenil Vati treatment. Hepatocyte necrosis, liver inflammation, and red blood cell (RBC) infiltration into the liver were significantly inhibited upon Denguenil treatment. Treatment with Denguenil Vati significantly recovered the virus-induced decreases in total platelet numbers and total RBC count, and concomitantly increasing hematocrit percentage, in a dose- and time-dependent manner. Conversely, virus-induced white blood cell (WBC) counts were significantly normalized. Virus-induced hemorrhage was completely abrogated by Denguenil after 14 days, at all the doses tested. Gene expression analysis identified a significant decrease in disease-induced endothelial apoptotic marker Angiopoetin2 (Ang-2) and pro-inflammatory chemokine marker CCL3 upon Denguenil treatment. Presence of gallic acid, ellagic acid, palmetin, and berberine molecules in the Denguenil formulation was detected by HPLC. Taken together, our results exhibit the potential therapeutic properties of Denguenil Vati in ameliorating pathological features of dengue. Full article
(This article belongs to the Special Issue Zebrafish: A Model for the Study of Human Diseases)
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