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Biomolecules, Volume 11, Issue 12 (December 2021) – 174 articles

Cover Story (view full-size image): The present article reviews the main therapeutic strategies proposed to treat multisystemic rare diseases named lysosomal storage disorders and determined by genetic variants, which affects proteins involved in lysosomal metabolism.The proposed approaches are based on the physiologic mechanisms that regulates lysosomal function and include enzyme replacement therapy, gene therapy, or small molecules. View this paper.
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14 pages, 2575 KiB  
Article
Sulfated Hyaluronan Modulates the Functional Properties and Matrix Effectors Expression of Breast Cancer Cells with Different Estrogen Receptor Status
by Christos Koutsakis, Anastasia-Gerasimoula Tavianatou, Dimitris Kokoretsis, Georgios Baroutas and Nikos K. Karamanos
Biomolecules 2021, 11(12), 1916; https://doi.org/10.3390/biom11121916 - 20 Dec 2021
Cited by 4 | Viewed by 3065
Abstract
Hyaluronan (HA) is an extracellular matrix glycosaminoglycan (GAG) that plays a pivotal role in breast cancer. While HA is the only GAG not normally substituted with sulfate groups, sulfated hyaluronan (sHA) has previously been used in studies with promising antitumor results. The aim [...] Read more.
Hyaluronan (HA) is an extracellular matrix glycosaminoglycan (GAG) that plays a pivotal role in breast cancer. While HA is the only GAG not normally substituted with sulfate groups, sulfated hyaluronan (sHA) has previously been used in studies with promising antitumor results. The aim of the present study was to evaluate the effects sHA fragments have on breast cancer cells with different estrogen receptor (ER) status. To this end, ERα-positive MCF-7, and ERβ-positive MDA-MB-231 cells were treated with non-sulfated HA or sHA fragments of 50 kDa. The functional properties of the breast cancer cells and the expression of key matrix effectors were investigated. According to the results, sHA attenuates cell proliferation, migration, and invasion, while increasing adhesion on collagen type I. Furthermore, sHA modulates the expression of epithelial-to-mesenchymal transition (EMT) markers, such as e-cadherin and snail2/slug. Additionally, sHA downregulates matrix remodeling enzymes such as the matrix metalloproteinases MT1-MMP, MMP2, and MMP9. Notably, sHA exhibits a stronger effect on the breast cancer cell properties compared to the non-sulfated counterpart, dependent also on the type of cancer cell type. Consequently, a deeper understanding of the mechanism by which sHA facilitate these processes could contribute to the development of novel therapeutic strategies. Full article
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22 pages, 7573 KiB  
Article
Bispecific Antibodies for IFN-β Delivery to ErbB2+ Tumors
by Vladislav S. Rybchenko, Anna A. Panina, Teimur K. Aliev, Olga N. Solopova, Dmitry S. Balabashin, Valery N. Novoseletsky, Dmitry A. Dolgikh, Petr G. Sveshnikov and Mikhail P. Kirpichnikov
Biomolecules 2021, 11(12), 1915; https://doi.org/10.3390/biom11121915 - 20 Dec 2021
Cited by 4 | Viewed by 2802
Abstract
The main aim of our work was to create a full-length bispecific antibody (BsAb) as a vehicle for the targeted delivery of interferon-beta (IFN-β) to ErbB2+ tumor cells in the form of non-covalent complex of BsAb and IFN-β. Such a construct is [...] Read more.
The main aim of our work was to create a full-length bispecific antibody (BsAb) as a vehicle for the targeted delivery of interferon-beta (IFN-β) to ErbB2+ tumor cells in the form of non-covalent complex of BsAb and IFN-β. Such a construct is a CrossMab-type BsAb, consisting of an ErbB2-recognizing trastuzumab moiety, a part of chimeric antibody to IFN-β, and human IgG1 Fc domain carrying knob-into-hole amino acid substitutions necessary for the proper assembly of bispecific molecules. The IFN-β- recognizing arm of BsAb not only forms a complex with the cytokine but neutralizes its activity, thus providing a mechanism to avoid the side effects of the systemic action of IFN-β by blocking IFN-β Interaction with cell receptors in the process of cytokine delivery to tumor sites. Enzyme sandwich immunoassay confirmed the ability of BsAb to bind to human IFN-β comparable to that of the parental chimeric mAb. The BsAb binds to the recombinant ErbB2 receptor, as well as to lysates of ErbB2+ tumor cell lines. The inhibition of the antiproliferative effect of IFN-β by BsAb (IC50 = 49,3 µg/mL) was demonstrated on the HT29 cell line. It can be proposed that the BsAb obtained can serve as a component of the immunocytokine complex for the delivery of IFN-β to ErbB2-associated tumor cells. Full article
(This article belongs to the Special Issue State-of-Art in Protein Engineering)
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46 pages, 1070 KiB  
Review
5-HT Receptors and Temperature Homeostasis
by Irina P. Voronova
Biomolecules 2021, 11(12), 1914; https://doi.org/10.3390/biom11121914 - 20 Dec 2021
Cited by 16 | Viewed by 3912
Abstract
The present review summarizes the data concerning the influence of serotonin (5-HT) receptors on body temperature in warm-blooded animals and on processes associated with its maintenance. This review includes the most important part of investigations from the first studies to the latest ones. [...] Read more.
The present review summarizes the data concerning the influence of serotonin (5-HT) receptors on body temperature in warm-blooded animals and on processes associated with its maintenance. This review includes the most important part of investigations from the first studies to the latest ones. The established results on the pharmacological activation of 5-HT1A, 5-HT3, 5-HT7 and 5-HT2 receptor types are discussed. Such activation of the first 3 type of receptors causes a decrease in body temperature, whereas the 5-HT2 activation causes its increase. Physiological mechanisms leading to changes in body temperature as a result of 5-HT receptors’ activation are discussed. In case of 5-HT1A receptor, they include an inhibition of shivering and non-shivering thermogenesis, as well simultaneous increase of peripheral blood flow, i.e., the processes of heat production and heat loss. The physiological processes mediated by 5-HT2 receptor are opposite to those of the 5-HT1A receptor. Mechanisms of 5-HT3 and 5-HT7 receptor participation in these processes are yet to be studied in more detail. Some facts indicating that in natural conditions, without pharmacological impact, these 5-HT receptors are important links in the system of temperature homeostasis, are also discussed. Full article
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16 pages, 1435 KiB  
Article
Sedimentary Cobalt Protoporphyrin as a Potential Precursor of Prosthetic Heme Group for Bacteria Inhabiting Fossil Organic Matter-Rich Shale Rock
by Robert Stasiuk and Renata Matlakowska
Biomolecules 2021, 11(12), 1913; https://doi.org/10.3390/biom11121913 - 20 Dec 2021
Cited by 1 | Viewed by 2122
Abstract
This study hypothesizes that bacteria inhabiting shale rock affect the content of the sedimentary cobalt protoporphyrin present in it and can use it as a precursor for heme synthesis. To verify this hypothesis, we conducted qualitative and quantitative comparative analyses of cobalt protoporphyrin [...] Read more.
This study hypothesizes that bacteria inhabiting shale rock affect the content of the sedimentary cobalt protoporphyrin present in it and can use it as a precursor for heme synthesis. To verify this hypothesis, we conducted qualitative and quantitative comparative analyses of cobalt protoporphyrin as well as heme, and heme iron in shale rock that were (i) inhabited by bacteria in the field, (ii) treated with bacteria in the laboratory, and with (iii) bacterial culture on synthetic cobalt protoporphyrin. Additionally, we examined the above-mentioned samples for the presence of enzymes involved in the heme biosynthesis and uptake as well as hemoproteins. We found depletion of cobalt protoporphyrin and a much higher heme concentration in the shale rock inhabited by bacteria in the field as well as the shale rock treated with bacteria in the laboratory. Similarly, we observed the accumulation of protoporphyrin in bacterial cells grown on synthetic cobalt protoporphyrin. We detected numerous hemoproteins in metaproteome of bacteria inhabited shale rock in the field and in proteomes of bacteria inhabited shale rock and synthetic cobalt protoporhyrin in the laboratory, but none of them had all the enzymes involved in the heme biosynthesis. However, proteins responsible for heme uptake, ferrochelatase and sirohydrochlorin cobaltochelatase/sirohydrochlorin cobalt-lyase were detected in all studied samples. Full article
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18 pages, 3853 KiB  
Review
Emerging Nanoparticle Strategies for Modulating Tumor-Associated Macrophage Polarization
by Lu Shi and Hongchen Gu
Biomolecules 2021, 11(12), 1912; https://doi.org/10.3390/biom11121912 - 20 Dec 2021
Cited by 11 | Viewed by 4510
Abstract
Immunotherapy has made great progress in recent years, yet the efficacy of solid tumors remains far less than expected. One of the main hurdles is to overcome the immune-suppressive tumor microenvironment (TME). Among all cells in TME, tumor-associated macrophages (TAMs) play pivotal roles [...] Read more.
Immunotherapy has made great progress in recent years, yet the efficacy of solid tumors remains far less than expected. One of the main hurdles is to overcome the immune-suppressive tumor microenvironment (TME). Among all cells in TME, tumor-associated macrophages (TAMs) play pivotal roles because of their abundance, multifaceted interactions to adaptive and host immune systems, as well as their context-dependent plasticity. Underlying the highly plastic characteristic, lots of research interests are focused on repolarizing TAMs from M2-like pro-tumor phenotype towards M1-like antitumoral ones. Nanotechnology offers great opportunities for targeting and modulating TAM polarization to mount the therapeutic efficacy in cancer immunotherapy. Here, this mini-review highlights those emerging nano-approaches for TAM repolarization in the last three years. Full article
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19 pages, 1064 KiB  
Review
The Cross Marks the Spot: The Emerging Role of JmjC Domain-Containing Proteins in Myeloid Malignancies
by Hans Felix Staehle, Heike Luise Pahl and Jonas Samuel Jutzi
Biomolecules 2021, 11(12), 1911; https://doi.org/10.3390/biom11121911 - 20 Dec 2021
Cited by 4 | Viewed by 3194
Abstract
Histone methylation tightly regulates chromatin accessibility, transcription, proliferation, and cell differentiation, and its perturbation contributes to oncogenic reprogramming of cells. In particular, many myeloid malignancies show evidence of epigenetic dysregulation. Jumonji C (JmjC) domain-containing proteins comprise a large and diverse group of histone [...] Read more.
Histone methylation tightly regulates chromatin accessibility, transcription, proliferation, and cell differentiation, and its perturbation contributes to oncogenic reprogramming of cells. In particular, many myeloid malignancies show evidence of epigenetic dysregulation. Jumonji C (JmjC) domain-containing proteins comprise a large and diverse group of histone demethylases (KDMs), which remove methyl groups from lysines in histone tails and other proteins. Cumulating evidence suggests an emerging role for these demethylases in myeloid malignancies, rendering them attractive targets for drug interventions. In this review, we summarize the known functions of Jumonji C (JmjC) domain-containing proteins in myeloid malignancies. We highlight challenges in understanding the context-dependent mechanisms of these proteins and explore potential future pharmacological targeting. Full article
(This article belongs to the Special Issue Jumonji Domain-Containing Proteins in Cancer Progression)
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14 pages, 2955 KiB  
Article
Prototype Foamy Virus Integrase Displays Unique Biochemical Activities among Retroviral Integrases
by Anthony J. Rabe, Yow Yong Tan, Ross C. Larue and Kristine E. Yoder
Biomolecules 2021, 11(12), 1910; https://doi.org/10.3390/biom11121910 - 20 Dec 2021
Cited by 2 | Viewed by 2457
Abstract
Integrases of different retroviruses assemble as functional complexes with varying multimers of the protein. Retroviral integrases require a divalent metal cation to perform one-step transesterification catalysis. Tetrameric prototype foamy virus (PFV) intasomes assembled from purified integrase and viral DNA oligonucleotides were characterized for [...] Read more.
Integrases of different retroviruses assemble as functional complexes with varying multimers of the protein. Retroviral integrases require a divalent metal cation to perform one-step transesterification catalysis. Tetrameric prototype foamy virus (PFV) intasomes assembled from purified integrase and viral DNA oligonucleotides were characterized for their activity in the presence of different cations. While most retroviral integrases are inactive in calcium, PFV intasomes appear to be uniquely capable of catalysis in calcium. The PFV intasomes also contrast with other retroviral integrases by displaying an inverse correlation of activity with increasing manganese beginning at relatively low concentrations. The intasomes were found to be significantly more active in the presence of chloride co-ions compared to acetate. While HIV-1 integrase appears to commit to a target DNA within 20 s, PFV intasomes do not commit to target DNA during their reaction lifetime. Together, these data highlight the unique biochemical activities of PFV integrase compared to other retroviral integrases. Full article
(This article belongs to the Section Enzymology)
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15 pages, 3227 KiB  
Article
Expression, Regulation, and Functions of the Galectin-16 Gene in Human Cells and Tissues
by Jennifer D. Kaminker and Alexander V. Timoshenko
Biomolecules 2021, 11(12), 1909; https://doi.org/10.3390/biom11121909 - 20 Dec 2021
Cited by 15 | Viewed by 3115
Abstract
Galectins comprise a family of soluble β-galactoside-binding proteins, which regulate a variety of key biological processes including cell growth, differentiation, survival, and death. This paper aims to address the current knowledge on the unique properties, regulation, and expression of the galectin-16 gene ( [...] Read more.
Galectins comprise a family of soluble β-galactoside-binding proteins, which regulate a variety of key biological processes including cell growth, differentiation, survival, and death. This paper aims to address the current knowledge on the unique properties, regulation, and expression of the galectin-16 gene (LGALS16) in human cells and tissues. To date, there are limited studies on this galectin, with most focusing on its tissue specificity to the placenta. Here, we report the expression and 8-Br-cAMP-induced upregulation of LGALS16 in two placental cell lines (BeWo and JEG-3) in the context of trophoblastic differentiation. In addition, we provide the results of a bioinformatics search for LGALS16 using datasets available at GEO, Human Protein Atlas, and prediction tools for relevant transcription factors and miRNAs. Our findings indicate that LGALS16 is detected by microarrays in diverse human cells/tissues and alters expression in association with cancer, diabetes, and brain diseases. Molecular mechanisms of the transcriptional and post-transcriptional regulation of LGALS16 are also discussed based on the available bioinformatics resources. Full article
(This article belongs to the Special Issue Cell Biology of Galectins)
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12 pages, 2119 KiB  
Article
Freeform 3D Bioprinting Involving Ink Gelation by Cascade Reaction of Oxidase and Peroxidase: A Feasibility Study Using Hyaluronic Acid-Based Ink
by Shinji Sakai, Ryohei Harada and Takashi Kotani
Biomolecules 2021, 11(12), 1908; https://doi.org/10.3390/biom11121908 - 20 Dec 2021
Cited by 7 | Viewed by 3627
Abstract
Freeform bioprinting, realized by extruding ink-containing cells into supporting materials to provide physical support during printing, has fostered significant advances toward the fabrication of cell-laden soft hydrogel constructs with desired spatial control. For further advancement of freeform bioprinting, we aimed to propose a [...] Read more.
Freeform bioprinting, realized by extruding ink-containing cells into supporting materials to provide physical support during printing, has fostered significant advances toward the fabrication of cell-laden soft hydrogel constructs with desired spatial control. For further advancement of freeform bioprinting, we aimed to propose a method in which the ink embedded in supporting materials gelate through a cytocompatible and rapid cascade reaction between oxidase and peroxidase. To demonstrate the feasibility of the proposed method, we extruded ink containing choline, horseradish peroxidase (HRP), and a hyaluronic acid derivative, cross-linkable by HRP-catalyzed reaction, into a supporting material containing choline oxidase and successfully obtained three-dimensional hyaluronic acid-based hydrogel constructs with good shape fidelity to blueprints. Cytocompatibility of the bioprinting method was confirmed by the comparable growth of mouse fibroblast cells, released from the printed hydrogels through degradation on cell culture dishes, with those not exposed to the printing process, and considering more than 85% viability of the enclosed cells during 10 days of culture. Owing to the presence of derivatives of the various biocompatible polymers that are cross-linkable through HRP-mediated cross-linking, our results demonstrate that the novel 3D bioprinting method has great potential in tissue engineering applications. Full article
(This article belongs to the Special Issue 3D Bioprinting for Biomedicine)
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12 pages, 607 KiB  
Review
Liver Regeneration and Cell Transplantation for End-Stage Liver Disease
by Yan Li, Lungen Lu and Xiaobo Cai
Biomolecules 2021, 11(12), 1907; https://doi.org/10.3390/biom11121907 - 20 Dec 2021
Cited by 13 | Viewed by 4194
Abstract
Liver transplantation is the only curative option for end-stage liver disease; however, the limitations of liver transplantation require further research into other alternatives. Considering that liver regeneration is prevalent in liver injury settings, regenerative medicine is suggested as a promising therapeutic strategy for [...] Read more.
Liver transplantation is the only curative option for end-stage liver disease; however, the limitations of liver transplantation require further research into other alternatives. Considering that liver regeneration is prevalent in liver injury settings, regenerative medicine is suggested as a promising therapeutic strategy for end-stage liver disease. Upon the source of regenerating hepatocytes, liver regeneration could be divided into two categories: hepatocyte-driven liver regeneration (typical regeneration) and liver progenitor cell-driven liver regeneration (alternative regeneration). Due to the massive loss of hepatocytes, the alternative regeneration plays a vital role in end-stage liver disease. Advances in knowledge of liver regeneration and tissue engineering have accelerated the progress of regenerative medicine strategies for end-stage liver disease. In this article, we generally reviewed the recent findings and current knowledge of liver regeneration, mainly regarding aspects of the histological basis of regeneration, histogenesis and mechanisms of hepatocytes’ regeneration. In addition, this review provides an update on the regenerative medicine strategies for end-stage liver disease. We conclude that regenerative medicine is a promising therapeutic strategy for end-stage liver disease. However, further studies are still required. Full article
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13 pages, 2738 KiB  
Article
Exploring the Cell Stemness and the Complexity of the Adipose Tissue Niche
by Nadav Kislev, Roza Izgilov, Raizel Adler and Dafna Benayahu
Biomolecules 2021, 11(12), 1906; https://doi.org/10.3390/biom11121906 - 19 Dec 2021
Cited by 8 | Viewed by 3122
Abstract
Adipose tissue is a complex organ composed of different cellular populations, including mesenchymal stem and progenitor cells, adipocytes, and immune cells such as macrophages and lymphocytes. These cellular populations alter dynamically during aging or as a response to pathophysiology such as obesity. Changes [...] Read more.
Adipose tissue is a complex organ composed of different cellular populations, including mesenchymal stem and progenitor cells, adipocytes, and immune cells such as macrophages and lymphocytes. These cellular populations alter dynamically during aging or as a response to pathophysiology such as obesity. Changes in the various inflammatory cells are associated with metabolic complications and the development of insulin resistance, indicating that immune cells crosstalk with the adipocytes. Therefore, a study of the cell populations in the adipose tissue and the extracellular matrix maintaining the tissue niche is important for the knowledge on the regulatory state of the organ. We used a combination of methods to study various parameters to identify the composition of the resident cells in the adipose tissue and evaluate their profile. We analyzed the tissue structure and cells based on histology, immune fluorescence staining, and flow cytometry of cells present in the tissue in vivo and these markers’ expression in vitro. Any shift in cells’ composition influences self-renewal of the mesenchymal progenitors, and other cells affect the functionality of adipogenesis. Full article
(This article belongs to the Collection Mesenchymal Stem Cell Fate and Potential Therapy)
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16 pages, 5840 KiB  
Article
A Computational Approach to Investigate TDP-43 RNA-Recognition Motif 2 C-Terminal Fragments Aggregation in Amyotrophic Lateral Sclerosis
by Greta Grassmann, Mattia Miotto, Lorenzo Di Rienzo, Federico Salaris, Beatrice Silvestri, Elsa Zacco, Alessandro Rosa, Gian Gaetano Tartaglia, Giancarlo Ruocco and Edoardo Milanetti
Biomolecules 2021, 11(12), 1905; https://doi.org/10.3390/biom11121905 - 19 Dec 2021
Cited by 5 | Viewed by 2782
Abstract
Many of the molecular mechanisms underlying the pathological aggregation of proteins observed in neurodegenerative diseases are still not fully understood. Among the aggregate-associated diseases, Amyotrophic Lateral Sclerosis (ALS) is of relevant importance. In fact, although understanding the processes that cause the disease is [...] Read more.
Many of the molecular mechanisms underlying the pathological aggregation of proteins observed in neurodegenerative diseases are still not fully understood. Among the aggregate-associated diseases, Amyotrophic Lateral Sclerosis (ALS) is of relevant importance. In fact, although understanding the processes that cause the disease is still an open challenge, its relationship with protein aggregation is widely known. In particular, human TDP-43, an RNA/DNA binding protein, is a major component of the pathological cytoplasmic inclusions observed in ALS patients. Indeed, the deposition of the phosphorylated full-length TDP-43 in spinal cord cells has been widely studied. Moreover, it has also been shown that the brain cortex presents an accumulation of phosphorylated C-terminal fragments (CTFs). Even if it is debated whether the aggregation of CTFs represents a primary cause of ALS, it is a hallmark of TDP-43 related neurodegeneration in the brain. Here, we investigate the CTFs aggregation process, providing a computational model of interaction based on the evaluation of shape complementarity at the molecular interfaces. To this end, extensive Molecular Dynamics (MD) simulations were conducted for different types of protein fragments, with the aim of exploring the equilibrium conformations. Adopting a newly developed approach based on Zernike polynomials, able to find complementary regions in the molecular surface, we sampled a large set of solvent-exposed portions of CTFs structures as obtained from MD simulations. Our analysis proposes and assesses a set of possible association mechanisms between the CTFs, which could drive the aggregation process of the CTFs. To further evaluate the structural details of such associations, we perform molecular docking and additional MD simulations to propose possible complexes and assess their stability, focusing on complexes whose interacting regions are both characterized by a high shape complementarity and involve β3 and β5 strands at their interfaces. Full article
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11 pages, 2120 KiB  
Article
A Deep Convolutional Neural Network for Prediction of Peptide Collision Cross Sections in Ion Mobility Spectrometry
by Yulia V. Samukhina, Dmitriy D. Matyushin, Oksana I. Grinevich and Aleksey K. Buryak
Biomolecules 2021, 11(12), 1904; https://doi.org/10.3390/biom11121904 - 19 Dec 2021
Cited by 4 | Viewed by 2765
Abstract
Most frequently, the identification of peptides in mass spectrometry-based proteomics is carried out using high-resolution tandem mass spectrometry. In order to increase the accuracy of analysis, additional information on the peptides such as chromatographic retention time and collision cross section in ion mobility [...] Read more.
Most frequently, the identification of peptides in mass spectrometry-based proteomics is carried out using high-resolution tandem mass spectrometry. In order to increase the accuracy of analysis, additional information on the peptides such as chromatographic retention time and collision cross section in ion mobility spectrometry can be used. An accurate prediction of the collision cross section values allows erroneous candidates to be rejected using a comparison of the observed values and the predictions based on the amino acids sequence. Recently, a massive high-quality data set of peptide collision cross sections was released. This opens up an opportunity to apply the most sophisticated deep learning techniques for this task. Previously, it was shown that a recurrent neural network allows for predicting these values accurately. In this work, we present a deep convolutional neural network that enables us to predict these values more accurately compared with previous studies. We use a neural network with complex architecture that contains both convolutional and fully connected layers and comprehensive methods of converting a peptide to multi-channel 1D spatial data and vector. The source code and pre-trained model are available online. Full article
(This article belongs to the Section Molecular Structure and Dynamics)
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24 pages, 415 KiB  
Review
Prebiotics, Probiotics, Synbiotics, Paraprobiotics and Postbiotic Compounds in IBD
by Adrian Martyniak, Aleksandra Medyńska-Przęczek, Andrzej Wędrychowicz, Szymon Skoczeń and Przemysław J. Tomasik
Biomolecules 2021, 11(12), 1903; https://doi.org/10.3390/biom11121903 - 18 Dec 2021
Cited by 61 | Viewed by 9954
Abstract
The increasing incidence of inflammatory bowel diseases (IBD) and the increasing severity of the course of these diseases create the need for developing new methods of therapy. The gut microbiome is extensively studied as a factor influencing the development and course of IBD. [...] Read more.
The increasing incidence of inflammatory bowel diseases (IBD) and the increasing severity of the course of these diseases create the need for developing new methods of therapy. The gut microbiome is extensively studied as a factor influencing the development and course of IBD. The composition of intestinal microbiota can be relatively easily modified by diet (i.e., prebiotics, mainly dietary fibers) and bacterial supplementation using beneficial bacteria strains called probiotics. Additionally, the effects of the improved microbiome could be enhanced or gained by using paraprobiotics (non-viable, inactivated bacteria or their components) and/or postbiotics (products of bacterial metabolism or equal synthetic products that beneficially modulate immunological response and inflammation). This study summarizes the recent works on prebiotics, probiotics, synbiotics (products merging pre- and probiotics), paraprobiotics and postbiotics in IBD. Full article
(This article belongs to the Special Issue Prebiotics and Probiotics in Health and Disease)
12 pages, 2741 KiB  
Article
The Assignment of the Absolute Configuration of Non-Cyclic Sesquiterpenes by Vibrational and Electronic Circular Dichroism: The Example of Chiliadenus lopadusanus Metabolites
by Giuseppe Mazzeo, Alessio Cimmino, Giovanna Longhi, Marco Masi, Antonio Evidente and Sergio Abbate
Biomolecules 2021, 11(12), 1902; https://doi.org/10.3390/biom11121902 - 18 Dec 2021
Cited by 2 | Viewed by 2234
Abstract
9-Hydroxynerolidol, 9-oxonerolidol, and chiliadenol B are three farnesane-type sesquiterpenoids isolated from Chiliadenus lopadusanus that have shown an interesting activity against human pathogens as Gram+ and Gram− bacteria resistant to antibiotics. However, the absolute configuration (AC) of these interesting sesquiterpenes has not been assigned [...] Read more.
9-Hydroxynerolidol, 9-oxonerolidol, and chiliadenol B are three farnesane-type sesquiterpenoids isolated from Chiliadenus lopadusanus that have shown an interesting activity against human pathogens as Gram+ and Gram− bacteria resistant to antibiotics. However, the absolute configuration (AC) of these interesting sesquiterpenes has not been assigned so far. Vibrational and electronic circular dichroism spectra have been recorded and correlations are pointed out for the three compounds. Density functional theory (DFT) calculations are used in conjunction with Mosher’s method of investigation to assign AC. Statistical analysis is considered to quantitatively define the choice of AC from VCD spectra. Full article
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19 pages, 1151 KiB  
Review
Impact of Food-Derived Bioactive Compounds on Intestinal Immunity
by Christian Zimmermann and Anika E. Wagner
Biomolecules 2021, 11(12), 1901; https://doi.org/10.3390/biom11121901 - 18 Dec 2021
Cited by 13 | Viewed by 4001
Abstract
The gastrointestinal system is responsible for the digestion and the absorption of nutrients. At the same time, it is essentially involved in the maintenance of immune homeostasis. The strongest antigen contact in an organism takes place in the digestive system showing the importance [...] Read more.
The gastrointestinal system is responsible for the digestion and the absorption of nutrients. At the same time, it is essentially involved in the maintenance of immune homeostasis. The strongest antigen contact in an organism takes place in the digestive system showing the importance of a host to develop mechanisms allowing to discriminate between harmful and harmless antigens. An efficient intestinal barrier and the presence of a large and complex part of the immune system in the gut support the host to implement this task. The continuous ingestion of harmless antigens via the diet requires an efficient immune response to reliably identify them as safe. However, in some cases the immune system accidentally identifies harmless antigens as dangerous leading to various diseases such as celiac disease, inflammatory bowel diseases and allergies. It has been shown that the intestinal immune function can be affected by bioactive compounds derived from the diet. The present review provides an overview on the mucosal immune reactions in the gut and how bioactive food ingredients including secondary plant metabolites and probiotics mediate its health promoting effects with regard to the intestinal immune homeostasis. Full article
(This article belongs to the Section Natural and Bio-inspired Molecules)
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30 pages, 8548 KiB  
Review
Keratinases as Versatile Enzymatic Tools for Sustainable Development
by Marcin Sypka, Iga Jodłowska and Aneta M. Białkowska
Biomolecules 2021, 11(12), 1900; https://doi.org/10.3390/biom11121900 - 18 Dec 2021
Cited by 22 | Viewed by 4606
Abstract
To reduce anthropological pressure on the environment, the implementation of novel technologies in present and future economies is needed for sustainable development. The food industry, with dairy and meat production in particular, has a significant environmental impact. Global poultry production is one of [...] Read more.
To reduce anthropological pressure on the environment, the implementation of novel technologies in present and future economies is needed for sustainable development. The food industry, with dairy and meat production in particular, has a significant environmental impact. Global poultry production is one of the fastest-growing meat producing sectors and is connected with the generation of burdensome streams of manure, offal and feather waste. In 2020, the EU alone produced around 3.2 million tonnes of poultry feather waste composed primarily of keratin, a protein biopolymer resistant to conventional proteolytic enzymes. If not managed properly, keratin waste can significantly affect ecosystems, contributing to environmental pollution, and pose a serious hazard to human and livestock health. In this article, the application of keratinolytic enzymes and microorganisms for promising novel keratin waste management methods with generation of new value-added products, such as bioactive peptides, vitamins, prion decontamination agents and biomaterials were reviewed. Full article
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51 pages, 16115 KiB  
Review
H2S Donors and Their Use in Medicinal Chemistry
by Elisa Magli, Elisa Perissutti, Vincenzo Santagada, Giuseppe Caliendo, Angela Corvino, Gianluca Esposito, Giovanna Esposito, Ferdinando Fiorino, Marco Migliaccio, Antonia Scognamiglio, Beatrice Severino, Rosa Sparaco and Francesco Frecentese
Biomolecules 2021, 11(12), 1899; https://doi.org/10.3390/biom11121899 - 18 Dec 2021
Cited by 36 | Viewed by 4435
Abstract
Hydrogen sulfide (H2S) is a ubiquitous gaseous signaling molecule that has an important role in many physiological and pathological processes in mammalian tissues, with the same importance as two others endogenous gasotransmitters such as NO (nitric oxide) and CO (carbon monoxide). [...] Read more.
Hydrogen sulfide (H2S) is a ubiquitous gaseous signaling molecule that has an important role in many physiological and pathological processes in mammalian tissues, with the same importance as two others endogenous gasotransmitters such as NO (nitric oxide) and CO (carbon monoxide). Endogenous H2S is involved in a broad gamut of processes in mammalian tissues including inflammation, vascular tone, hypertension, gastric mucosal integrity, neuromodulation, and defense mechanisms against viral infections as well as SARS-CoV-2 infection. These results suggest that the modulation of H2S levels has a potential therapeutic value. Consequently, synthetic H2S-releasing agents represent not only important research tools, but also potent therapeutic agents. This review has been designed in order to summarize the currently available H2S donors; furthermore, herein we discuss their preparation, the H2S-releasing mechanisms, and their -biological applications. Full article
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15 pages, 3881 KiB  
Communication
Transport and Secretion of the Wnt3 Ligand by Motor Neuron-like Cells and Developing Motor Neurons
by Cristina Pinto, Viviana Pérez, Jessica Mella, Miguel Albistur, Teresa Caprile, Francisca C. Bronfman and Juan Pablo Henríquez
Biomolecules 2021, 11(12), 1898; https://doi.org/10.3390/biom11121898 - 17 Dec 2021
Cited by 4 | Viewed by 2623
Abstract
The vertebrate neuromuscular junction (NMJ) is formed by a presynaptic motor nerve terminal and a postsynaptic muscle specialization. Cumulative evidence reveals that Wnt ligands secreted by the nerve terminal control crucial steps of NMJ synaptogenesis. For instance, the Wnt3 ligand is expressed by [...] Read more.
The vertebrate neuromuscular junction (NMJ) is formed by a presynaptic motor nerve terminal and a postsynaptic muscle specialization. Cumulative evidence reveals that Wnt ligands secreted by the nerve terminal control crucial steps of NMJ synaptogenesis. For instance, the Wnt3 ligand is expressed by motor neurons at the time of NMJ formation and induces postsynaptic differentiation in recently formed muscle fibers. However, the behavior of presynaptic-derived Wnt ligands at the vertebrate NMJ has not been deeply analyzed. Here, we conducted overexpression experiments to study the expression, distribution, secretion, and function of Wnt3 by transfection of the motor neuron-like NSC-34 cell line and by in ovo electroporation of chick motor neurons. Our findings reveal that Wnt3 is transported along motor axons in vivo following a vesicular-like pattern and reaches the NMJ area. In vitro, we found that endogenous Wnt3 expression increases as the differentiation of NSC-34 cells proceeds. Although NSC-34 cells overexpressing Wnt3 do not modify their morphological differentiation towards a neuronal phenotype, they effectively induce acetylcholine receptor clustering on co-cultured myotubes. These findings support the notion that presynaptic Wnt3 is transported and secreted by motor neurons to induce postsynaptic differentiation in nascent NMJs. Full article
(This article belongs to the Special Issue The Neuromuscular Junction in Health and Disease)
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11 pages, 2346 KiB  
Article
Allelic Variation Analysis at the Vernalization Response and Photoperiod Genes in Russian Wheat Varieties Identified Two Novel Alleles of Vrn-B3
by Alina Berezhnaya, Antonina Kiseleva, Irina Leonova and Elena Salina
Biomolecules 2021, 11(12), 1897; https://doi.org/10.3390/biom11121897 - 17 Dec 2021
Cited by 10 | Viewed by 2502
Abstract
Heading time is an important agronomic trait affecting the adaptability and productivity of common wheat. In this study, 95 common wheat varieties from Russia and the late-maturing breeding line ‘Velut’ were tested for allelic diversity of genes having the strongest effect on heading. [...] Read more.
Heading time is an important agronomic trait affecting the adaptability and productivity of common wheat. In this study, 95 common wheat varieties from Russia and the late-maturing breeding line ‘Velut’ were tested for allelic diversity of genes having the strongest effect on heading. In this research, allelic variation at the Ppd-D1, Vrn-A1, Vrn-B1, Vrn-D1, and Vrn-B3 loci was tested. The Vrn-B1 and Vrn-B3 loci provided the largest contribution to genetic diversity. We found two novel allelic variants of the Vrn-B3 gene in the studied varieties. Ten varieties carried a 160 bp insertion in the promoter region, and the breeding line ‘Velut’ carried a 1617 bp insertion. These alleles were designated Vrn-B3e and Vrn-B3d, respectively. The analysis of the sequences showed the recent insertion of a retrotransposon homologous to the LTR retrotransposon (RLX_Hvul_Dacia_ RND-1) in the Vrn-B3d allele. Plants with the Vrn-B3e and the ‘Velut’ line with the Vrn-B3d allele headed later than the plants with the wild-type allele; among these plants, ‘Velut’ is the latest maturing wheat variety. Analysis of the gene expression of two groups of lines differing by the Vrn-B3 alleles (Vrn-B3d or vrn-B3) from the F2 population with ‘Velut’ as a parental line did not reveal a significant difference in the expression level between the groups. Additional research is required to study the reasons for the late maturation of the ‘Velut’ line. However, the studied wheat varieties could be used as a potential source of natural variation in genes controlling heading times. Full article
(This article belongs to the Special Issue Molecular-Genetic Bases of Plant Breeding)
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14 pages, 1347 KiB  
Article
Dexamethasone for Inner Ear Therapy: Biocompatibility and Bio-Efficacy of Different Dexamethasone Formulations In Vitro
by Ziwen Gao, Jana Schwieger, Farnaz Matin-Mann, Peter Behrens, Thomas Lenarz and Verena Scheper
Biomolecules 2021, 11(12), 1896; https://doi.org/10.3390/biom11121896 - 17 Dec 2021
Cited by 9 | Viewed by 3261
Abstract
Dexamethasone is widely used in preclinical studies and clinical trials to treat inner ear disorders. The results of those studies vary widely, maybe due to the different dexamethasone formulations used. Laboratory (lab) and medical grade (med) dexamethasone (DEX, C22H29FO [...] Read more.
Dexamethasone is widely used in preclinical studies and clinical trials to treat inner ear disorders. The results of those studies vary widely, maybe due to the different dexamethasone formulations used. Laboratory (lab) and medical grade (med) dexamethasone (DEX, C22H29FO5) and dexamethasone dihydrogen phosphate-disodium (DPS, C22H28FNa2O8P) were investigated for biocompatibility and bio-efficacy in vitro. The biocompatibility of each dexamethasone formulation in concentrations from 0.03 to 10,000 µM was evaluated using an MTT assay. The concentrations resulting in the highest cell viability were selected to perform a bio-efficiency test using a TNFα-reduction assay. All dexamethasone formulations up to 900 µM are biocompatible in vitro. DPS-lab becomes toxic at 1000 µM and DPS-med at 2000 µM, while DEX-lab and DEX-med become toxic at 4000 µM. Bio-efficacy was evaluated for DEX-lab and DPS-med at 300 µM, for DEX-med at 60 µM, and DPS-lab at 150 µM, resulting in significantly reduced expression of TNFα, with DPS-lab having the highest effect. Different dexamethasone formulations need to be applied in different concentration ranges to be biocompatible. The concentration to be applied in future studies should carefully be chosen based on the respective dexamethasone form, application route and duration to ensure biocompatibility and bio-efficacy. Full article
(This article belongs to the Special Issue Inner Ear Therapeutics)
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2 pages, 652 KiB  
Correction
Correction: Fernandes et al. Stress Granule Assembly Can Facilitate but Is Not Required for TDP-43 Cytoplasmic Aggregation. Biomolecules 2020, 10, 1367
by Nikita Fernandes, Luke Nero, Shawn M. Lyons, Pavel Ivanov, Telsa M. Mittelmeier, Timothy A. Bolger and J. Ross Buchan
Biomolecules 2021, 11(12), 1895; https://doi.org/10.3390/biom11121895 - 17 Dec 2021
Viewed by 1811
Abstract
In the original article [...] Full article
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21 pages, 916 KiB  
Review
Bioactive Antimicrobial Peptides as Therapeutic Agents for Infected Diabetic Foot Ulcers
by Jessica Da Silva, Ermelindo C. Leal and Eugénia Carvalho
Biomolecules 2021, 11(12), 1894; https://doi.org/10.3390/biom11121894 - 17 Dec 2021
Cited by 20 | Viewed by 5465
Abstract
Diabetic foot ulcer (DFU) is a devastating complication, affecting around 15% of diabetic patients and representing a leading cause of non-traumatic amputations. Notably, the risk of mixed bacterial–fungal infection is elevated and highly associated with wound necrosis and poor clinical outcomes. However, it [...] Read more.
Diabetic foot ulcer (DFU) is a devastating complication, affecting around 15% of diabetic patients and representing a leading cause of non-traumatic amputations. Notably, the risk of mixed bacterial–fungal infection is elevated and highly associated with wound necrosis and poor clinical outcomes. However, it is often underestimated in the literature. Therefore, polymicrobial infection control must be considered for effective management of DFU. It is noteworthy that antimicrobial resistance is constantly rising overtime, therefore increasing the need for new alternatives to antibiotics and antifungals. Antimicrobial peptides (AMPs) are endogenous peptides that are naturally abundant in several organisms, such as bacteria, amphibians and mammals, particularly in the skin. These molecules have shown broad-spectrum antimicrobial activity and some of them even have wound-healing activity, establishing themselves as ideal candidates for treating multi-kingdom infected wounds. Furthermore, the role of AMPs with antifungal activity in wound management is poorly described and deserves further investigation in association with antibacterial agents, such as antibiotics and AMPs with antibacterial activity, or alternatively the application of broad-spectrum antimicrobial agents that target both aerobic and anaerobic bacteria, as well as fungi. Accordingly, the aim of this review is to unravel the molecular mechanisms by which AMPs achieve their dual antimicrobial and wound-healing properties, and to discuss how these are currently being applied as promising therapies against polymicrobial-infected chronic wounds such as DFUs. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Wound Healing)
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12 pages, 920 KiB  
Article
Anthelmintic Activity and Cytotoxic Effects of Compounds Isolated from the Fruits of Ozoroa insignis Del. (Anacardiaceae)
by Mthandazo Dube, Mohamad Saoud, Robert Rennert, Ghislain Wabo Fotso, Kerstin Andrae-Marobela, Peter Imming, Cécile Häberli, Jennifer Keiser and Norbert Arnold
Biomolecules 2021, 11(12), 1893; https://doi.org/10.3390/biom11121893 - 17 Dec 2021
Cited by 6 | Viewed by 2709
Abstract
Ozoroa insignis Del. is an ethnobotanical plant widely used in traditional medicine for various ailments, including schistosomiasis, tapeworm, and hookworm infections. From the so far not investigated fruits of Ozoroa insignis, the anthelmintic principles could be isolated through bioassay-guided isolation using Caenorhabditis [...] Read more.
Ozoroa insignis Del. is an ethnobotanical plant widely used in traditional medicine for various ailments, including schistosomiasis, tapeworm, and hookworm infections. From the so far not investigated fruits of Ozoroa insignis, the anthelmintic principles could be isolated through bioassay-guided isolation using Caenorhabditis elegans and identified by NMR spectroscopic analysis and mass spectrometric studies. Isolated 6-[8(Z)-pentadecenyl] anacardic (1), 6-[10(Z)-heptadecenyl] anacardic acid (2), and 3-[7(Z)-pentadecenyl] phenol (3) were evaluated against the 5 parasitic organisms Schistosoma mansoni (adult and newly transformed schistosomula), Strongyloides ratti, Heligmosomoides polygyrus, Necator americanus, and Ancylostoma ceylanicum, which mainly infect humans and other mammals. Compounds 13 showed good activity against Schistosoma mansoni, with compound 1 showing the best activity against newly transformed schistosomula with 50% activity at 1µM. The isolated compounds were also evaluated for their cytotoxic properties against PC-3 (human prostate adenocarcinoma) and HT-29 (human colorectal adenocarcinoma) cell lines, whereby compounds 2 and 3 showed antiproliferative activity in both cancer cell lines, while compound 1 exhibited antiproliferative activity only on PC-3 cells. With an IC50 value of 43.2 µM, compound 3 was found to be the most active of the 3 investigated compounds. Full article
(This article belongs to the Special Issue Bioactive Natural Compounds against Animal and Human Pathogens)
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20 pages, 3249 KiB  
Article
Gut Metabolite Trimethylamine N-Oxide Protects INS-1 β-Cell and Rat Islet Function under Diabetic Glucolipotoxic Conditions
by Emily S. Krueger, Joseph L. Beales, Kacie B. Russon, Weston S. Elison, Jordan R. Davis, Jackson M. Hansen, Andrew P. Neilson, Jason M. Hansen and Jeffery S. Tessem
Biomolecules 2021, 11(12), 1892; https://doi.org/10.3390/biom11121892 - 17 Dec 2021
Cited by 12 | Viewed by 3407
Abstract
Serum accumulation of the gut microbial metabolite trimethylamine N-oxide (TMAO) is associated with high caloric intake and type 2 diabetes (T2D). Impaired pancreatic β-cell function is a hallmark of diet-induced T2D, which is linked to hyperglycemia and hyperlipidemia. While TMAO production via the [...] Read more.
Serum accumulation of the gut microbial metabolite trimethylamine N-oxide (TMAO) is associated with high caloric intake and type 2 diabetes (T2D). Impaired pancreatic β-cell function is a hallmark of diet-induced T2D, which is linked to hyperglycemia and hyperlipidemia. While TMAO production via the gut microbiome-liver axis is well defined, its molecular effects on metabolic tissues are unclear, since studies in various tissues show deleterious and beneficial TMAO effects. We investigated the molecular effects of TMAO on functional β-cell mass. We hypothesized that TMAO may damage functional β-cell mass by inhibiting β-cell viability, survival, proliferation, or function to promote T2D pathogenesis. We treated INS-1 832/13 β-cells and primary rat islets with physiological TMAO concentrations and compared functional β-cell mass under healthy standard cell culture (SCC) and T2D-like glucolipotoxic (GLT) conditions. GLT significantly impeded β-cell mass and function by inducing oxidative and endoplasmic reticulum (ER) stress. TMAO normalized GLT-mediated damage in β-cells and primary islet function. Acute 40µM TMAO recovered insulin production, insulin granule formation, and insulin secretion by upregulating the IRE1α unfolded protein response to GLT-induced ER and oxidative stress. These novel results demonstrate that TMAO protects β-cell function and suggest that TMAO may play a beneficial molecular role in diet-induced T2D conditions. Full article
(This article belongs to the Special Issue The Pancreatic Beta Cell)
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17 pages, 2802 KiB  
Article
Sterol Extraction from Isolated Plant Plasma Membrane Vesicles Affects H+-ATPase Activity and H+-Transport
by Nikita K. Lapshin, Michail S. Piotrovskii and Marina S. Trofimova
Biomolecules 2021, 11(12), 1891; https://doi.org/10.3390/biom11121891 - 16 Dec 2021
Cited by 2 | Viewed by 2176
Abstract
Plasma membrane H+-ATPase is known to be detected in detergent-resistant sterol-enriched fractions, also called “raft” domains. Studies on H+-ATPase reconstituted in artificial or native membrane vesicles have shown both sterol-mediated stimulations and inhibitions of its activity. Here, using sealed [...] Read more.
Plasma membrane H+-ATPase is known to be detected in detergent-resistant sterol-enriched fractions, also called “raft” domains. Studies on H+-ATPase reconstituted in artificial or native membrane vesicles have shown both sterol-mediated stimulations and inhibitions of its activity. Here, using sealed isolated plasma membrane vesicles, we investigated the effects of sterol depletion in the presence of methyl-β-cyclodextrin (MβCD) on H+-ATPase activity. The rate of ATP-dependent ∆µH+ generation and the kinetic parameters of ATP hydrolysis were evaluated. We show that the relative sterols content in membrane vesicles decreased gradually after treatment with MβCD and reached approximately 40% of their initial level in 30 mM probe solution. However, changes in the hydrolytic and H+-transport activities of the enzyme were nonlinear. The extraction of up to 20% of the initial sterols was accompanied by strong stimulation of ATP-dependent H+-transport in comparison with the hydrolytic activity of enzymes. Further sterol depletion led to a significant inhibition of active proton transport with an increase in passive H+-leakage. The solubilization of control and sterol-depleted vesicles in the presence of dodecyl maltoside negated the differences in the kinetics parameters of ATP hydrolysis, and all samples demonstrated maximal hydrolytic activities. The mechanisms behind the sensitivity of ATP-dependent H+-transport to sterols in the lipid environment of plasma membrane H+-ATPase are discussed. Full article
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12 pages, 2014 KiB  
Article
Inhibition of LPMOs by Fermented Persimmon Juice
by Radina Tokin, Johan Ørskov Ipsen, Mahesha M. Poojary, Poul Erik Jensen, Lisbeth Olsson and Katja Salomon Johansen
Biomolecules 2021, 11(12), 1890; https://doi.org/10.3390/biom11121890 - 16 Dec 2021
Cited by 3 | Viewed by 2639
Abstract
Fermented persimmon juice, Kakishibu, has traditionally been used for wood and paper protection. This protective effect stems at least partially from inhibition of microbial cellulose degrading enzymes. The inhibitory effect of Kakishibu on lytic polysaccharide monooxygenases (LPMOs) and on a cocktail of cellulose [...] Read more.
Fermented persimmon juice, Kakishibu, has traditionally been used for wood and paper protection. This protective effect stems at least partially from inhibition of microbial cellulose degrading enzymes. The inhibitory effect of Kakishibu on lytic polysaccharide monooxygenases (LPMOs) and on a cocktail of cellulose hydrolases was studied, using three different cellulosic substrates. Dose dependent inhibition of LPMO activity by a commercial Kakishibu product was assessed for the well-characterized LPMO from Thermoascus aurantiacus TaAA9A, and the inhibitory effect was confirmed on five additional microbial LPMOs. The model tannin compound, tannic acid exhibited a similar inhibitory effect on TaAA9A as Kakishibu. It was further shown that both polyethylene glycol and tannase can alleviate the inhibitory effect of Kakishibu and tannic acid, indicating a likely mechanism of inhibition caused by unspecific tannin–protein interactions. Full article
(This article belongs to the Special Issue Lytic Polysaccharide Monooxygenases: Diversity and Molecular Events)
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14 pages, 1890 KiB  
Article
A Time-Kill Assay Study on the Synergistic Bactericidal Activity of Pomegranate Rind Extract and Zn (II) against Methicillin-Resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa
by Amal Alrashidi, Mohammed Jafar, Niamh Higgins, Ciara Mulligan, Carmine Varricchio, Ryan Moseley, Vildan Celiksoy, David M. J. Houston and Charles M. Heard
Biomolecules 2021, 11(12), 1889; https://doi.org/10.3390/biom11121889 - 16 Dec 2021
Cited by 4 | Viewed by 2807
Abstract
There is a need for new antimicrobial systems due to increased global resistance to current antimicrobials. Pomegranate rind extract (PRE) and Zn (II) ions both possess a level of antimicrobial activity and work has previously shown that PRE/Zn (II) in combination possesses synergistic [...] Read more.
There is a need for new antimicrobial systems due to increased global resistance to current antimicrobials. Pomegranate rind extract (PRE) and Zn (II) ions both possess a level of antimicrobial activity and work has previously shown that PRE/Zn (II) in combination possesses synergistic activity against Herpes simplex virus and Micrococcus luteus. Here, we determined whether such synergistic activity extended to other, more pathogenic, bacteria. Reference strains of methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa were cultured and subjected to challenge by PRE, Zn (II), or PRE + Zn (II), in time-kill assays. Data were obtained independently by two researchers using different PRE preparations. Statistically significant synergistic activity for PRE + Zn (II) was shown for all four bacterial strains tested compared to untreated controls, although the extent of efficacy and timescales varied. Zn (II) exerted activity and at 1 h, it was not possible to distinguish with PRE + Zn (II) combination treatment in all cases. PRE alone showed low activity against all four bacteria. Reproducible synergistic bactericidal activity involving PRE and Zn (II) has been confirmed. Potential mechanisms are discussed. The development of a therapeutic system that possesses demonstrable antimicrobial activity is supported which lends itself particularly to topical delivery applications, for example MRSA infections. Full article
(This article belongs to the Special Issue Bioactive Natural Compounds against Animal and Human Pathogens)
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19 pages, 2872 KiB  
Article
Metformin Treatment or PRODH/POX-Knock out Similarly Induces Apoptosis by Reprograming of Amino Acid Metabolism, TCA, Urea Cycle and Pentose Phosphate Pathway in MCF-7 Breast Cancer Cells
by Thi Yen Ly Huynh, Ilona Oscilowska, Jorge Sáiz, Magdalena Nizioł, Weronika Baszanowska, Coral Barbas and Jerzy Palka
Biomolecules 2021, 11(12), 1888; https://doi.org/10.3390/biom11121888 - 15 Dec 2021
Cited by 6 | Viewed by 3329
Abstract
It has been considered that proline dehydrogenase/proline oxidase (PRODH/POX) is involved in antineoplastic activity of metformin (MET). The aim of this study is identification of key metabolites of glycolysis, pentose phosphate pathway (PPP), tricarboxylic acids (TCA), urea cycles (UC) and some amino acids [...] Read more.
It has been considered that proline dehydrogenase/proline oxidase (PRODH/POX) is involved in antineoplastic activity of metformin (MET). The aim of this study is identification of key metabolites of glycolysis, pentose phosphate pathway (PPP), tricarboxylic acids (TCA), urea cycles (UC) and some amino acids in MET-treated MCF-7 cells and PRODH/POX-knocked out MCF-7 (MCF-7crPOX) cells. MCF-7crPOX cells were generated by using CRISPR-Cas9. Targeted metabolomics was performed by LC-MS/MS/QqQ. Expression of pro-apoptotic proteins was evaluated by Western blot. In the absence of glutamine, MET treatment or PRODH/POX-knock out of MCF-7 cells contributed to similar inhibition of glycolysis (drastic increase in intracellular glucose and pyruvate) and increase in the utilization of phospho-enol-pyruvic acid, glucose-6-phosphate and some metabolites of TCA and UC, contributing to apoptosis. However, in the presence of glutamine, MET treatment or PRODH/POX-knock out of MCF-7 cells contributed to utilization of some studied metabolites (except glucose), facilitating pro-survival phenotype of MCF-7 cells in these conditions. It suggests that MET treatment or PRODH/POX-knock out induce similar metabolic effects (glucose starvation) and glycolysis is tightly linked to glutamine metabolism in MCF-7 breast cancer cells. The data provide insight into mechanism of anticancer activity of MET as an approach to further studies on experimental breast cancer therapy. Full article
(This article belongs to the Section Cellular Biochemistry)
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14 pages, 793 KiB  
Review
Four Seasons for Schwann Cell Biology, Revisiting Key Periods: Development, Homeostasis, Repair, and Aging
by Gabriela Sardella-Silva, Bruno Siqueira Mietto and Victor Túlio Ribeiro-Resende
Biomolecules 2021, 11(12), 1887; https://doi.org/10.3390/biom11121887 - 15 Dec 2021
Cited by 12 | Viewed by 3579
Abstract
Like the seasons of the year, all natural things happen in stages, going through adaptations when challenged, and Schwann cells are a great example of that. During maturation, these cells regulate several steps in peripheral nervous system development. The Spring of the cell [...] Read more.
Like the seasons of the year, all natural things happen in stages, going through adaptations when challenged, and Schwann cells are a great example of that. During maturation, these cells regulate several steps in peripheral nervous system development. The Spring of the cell means the rise and bloom through organized stages defined by time-dependent regulation of factors and microenvironmental influences. Once matured, the Summer of the cell begins: a high energy stage focused on maintaining adult homeostasis. The Schwann cell provides many neuron-glia communications resulting in the maintenance of synapses. In the peripheral nervous system, Schwann cells are pivotal after injuries, balancing degeneration and regeneration, similarly to when Autumn comes. Their ability to acquire a repair phenotype brings the potential to reconnect axons to targets and regain function. Finally, Schwann cells age, not only by growing old, but also by imposed environmental cues, like loss of function induced by pathologies. The Winter of the cell presents as reduced activity, especially regarding their role in repair; this reflects on the regenerative potential of older/less healthy individuals. This review gathers essential information about Schwann cells in different stages, summarizing important participation of this intriguing cell in many functions throughout its lifetime. Full article
(This article belongs to the Special Issue Recent Advances in Schwann Cells)
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