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Biology
Volume 9
Issue 12
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Biology, Volume 9, Issue 12 (December 2020) – 75 articles

Cover Story (view full-size image): Mollusca form an important component of the ecosystem and food chain, with considerable global commercial value. They are affected by anthropogenic changes, pollution, climate change and opportunistic infections. Changes in their immune responses can indicate changes in ocean environments. Therefore, studies on Mollusca immune systems are important to aid in novel biomarker discovery. This study assessed extracellular vesicles and post-translational protein deimination profiles in four economically important Bivalvia: blue mussel, soft shell clam, Eastern oyster and Atlantic jackknife clam. Our findings show regulatory mechanisms via the deimination of key metabolic and immunology related pathways in Mollusca. The findings contribute to current understanding of the diverse functions of these pathways throughout the phylogeny tree and aid in new aquaculture biomarker discovery. View this paper.
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18 pages, 1824 KiB  
Review
Mitochondrial microRNAs: A Putative Role in Tissue Regeneration
by Sílvia C. Rodrigues, Renato M. S. Cardoso and Filipe V. Duarte
Biology 2020, 9(12), 486; https://doi.org/10.3390/biology9120486 - 21 Dec 2020
Cited by 5 | Viewed by 4427
Abstract
The most famous role of mitochondria is to generate ATP through oxidative phosphorylation, a metabolic pathway that involves a chain of four protein complexes (the electron transport chain, ETC) that generates a proton-motive force that in turn drives the ATP synthesis by the [...] Read more.
The most famous role of mitochondria is to generate ATP through oxidative phosphorylation, a metabolic pathway that involves a chain of four protein complexes (the electron transport chain, ETC) that generates a proton-motive force that in turn drives the ATP synthesis by the Complex V (ATP synthase). An impressive number of more than 1000 mitochondrial proteins have been discovered. Since mitochondrial proteins have a dual genetic origin, it is predicted that ~99% of these proteins are nuclear-encoded and are synthesized in the cytoplasmatic compartment, being further imported through mitochondrial membrane transporters. The lasting 1% of mitochondrial proteins are encoded by the mitochondrial genome and synthesized by the mitochondrial ribosome (mitoribosome). As a result, an appropriate regulation of mitochondrial protein synthesis is absolutely required to achieve and maintain normal mitochondrial function. Regarding miRNAs in mitochondria, it is well-recognized nowadays that several cellular mechanisms involving mitochondria are regulated by many genetic players that originate from either nuclear- or mitochondrial-encoded small noncoding RNAs (sncRNAs). Growing evidence collected from whole genome and transcriptome sequencing highlight the role of distinct members of this class, from short interfering RNAs (siRNAs) to miRNAs and long noncoding RNAs (lncRNAs). Some of the mechanisms that have been shown to be modulated are the expression of mitochondrial proteins itself, as well as the more complex coordination of mitochondrial structure and dynamics with its function. We devote particular attention to the role of mitochondrial miRNAs and to their role in the modulation of several molecular processes that could ultimately contribute to tissue regeneration accomplishment. Full article
(This article belongs to the Collection Mitochondria and Stress Responses)
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16 pages, 671 KiB  
Review
The Senescence-Associated Secretory Phenotype (SASP) in the Challenging Future of Cancer Therapy and Age-Related Diseases
by Lorenzo Cuollo, Fabrizio Antonangeli, Angela Santoni and Alessandra Soriani
Biology 2020, 9(12), 485; https://doi.org/10.3390/biology9120485 - 21 Dec 2020
Cited by 142 | Viewed by 14755
Abstract
Cellular senescence represents a robust tumor-protecting mechanism that halts the proliferation of stressed or premalignant cells. However, this state of stable proliferative arrest is accompanied by the Senescence-Associated Secretory Phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment [...] Read more.
Cellular senescence represents a robust tumor-protecting mechanism that halts the proliferation of stressed or premalignant cells. However, this state of stable proliferative arrest is accompanied by the Senescence-Associated Secretory Phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment and contributes to age-related conditions, including, paradoxically, cancer. Novel therapeutic strategies aim at eliminating senescent cells with the use of senolytics or abolishing the SASP without killing the senescent cell with the use of the so-called “senomorphics”. In addition, recent works demonstrate the possibility of modifying the composition of the secretome by genetic or pharmacological intervention. The purpose is not to renounce the potent immunostimulatory nature of SASP, but rather learning to modulate it for combating cancer and other age-related diseases. This review describes the main molecular mechanisms regulating the SASP and reports the evidence of the feasibility of abrogating or modulating the SASP, discussing the possible implications of both strategies. Full article
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21 pages, 386 KiB  
Review
A Descriptive Overview of the Medical Uses Given to Mentha Aromatic Herbs throughout History
by Henrique Silva
Biology 2020, 9(12), 484; https://doi.org/10.3390/biology9120484 - 21 Dec 2020
Cited by 17 | Viewed by 7701
Abstract
Mints have been among the most widely used herbs for medicinal purposes since ancient civilizations. They are still presently used for numerous purposes, including non-medicinal, which makes them economically relevant herbs. Information regarding the medical and scientific uses given to mints throughout history [...] Read more.
Mints have been among the most widely used herbs for medicinal purposes since ancient civilizations. They are still presently used for numerous purposes, including non-medicinal, which makes them economically relevant herbs. Information regarding the medical and scientific uses given to mints throughout history are vastly scattered and/or incomplete. The aim of this paper is to provide an extensive descriptive overview of the medical uses given to these herbs, highlighting both the authors in medical culture responsible for their dissemination, as well as their major galenic formulations. Databases on medical science, reference textbooks on medical history, botanics (aromatic herbs), and pharmacognosy were consulted. The use of mints remotes to Classical Antiquity, with major contributions from Pliny the Elder. In the Middle Ages, the increased knowledge surrounding mints came from Byzantine physicians, while, in the Modern Age, technological developments allowed the production of mint-based products which have become part of elaborate galenic formulas employed by an increasing number of physicians, as well as have also stimulated both scientific and artistic interests alike. In present-day medicine, several mints and mint-based products are being researched as potential therapeutic alternatives for many diseases, while also being vastly employed in food and cosmetic industries. Full article
(This article belongs to the Special Issue Bioactivity of Medicinal Plants and Extracts)
9 pages, 3915 KiB  
Technical Note
Multipath: An R Package to Generate Integrated Reproducible Pathway Models
by Zaynab Hammoud and Frank Kramer
Biology 2020, 9(12), 483; https://doi.org/10.3390/biology9120483 - 21 Dec 2020
Cited by 3 | Viewed by 2821
Abstract
Biological pathway data integration has become a topic of interest in the past years. This interest originates essentially from the continuously increasing size of existing prior knowledge as well as from the many challenges scientists face when studying biological pathways. Multipath is a [...] Read more.
Biological pathway data integration has become a topic of interest in the past years. This interest originates essentially from the continuously increasing size of existing prior knowledge as well as from the many challenges scientists face when studying biological pathways. Multipath is a framework that aims at helping re-trace the use of specific pathway knowledge in specific publications, and easing the data integration of multiple pathway types and further influencing knowledge sources. Multipath thus helps scientists to increase the reproducibility of their code and analysis by allowing the integration of numerous data sources and documentation of their integration steps while doing so. In this paper, we present the package Multipath, and we describe how it can be used for data integration and tracking pathway modifications. We present a multilayer model built from the Wnt Pathway as a demonstration. Full article
(This article belongs to the Special Issue Computational Biology)
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18 pages, 2997 KiB  
Article
Genome Sequences of Serratia Strains Revealed Common Genes in Both Serratomolides Gene Clusters
by Catarina Marques-Pereira, Diogo Neves Proença and Paula V. Morais
Biology 2020, 9(12), 482; https://doi.org/10.3390/biology9120482 - 20 Dec 2020
Cited by 9 | Viewed by 4171
Abstract
Serratia strains are ubiquitous microorganisms with the ability to produce serratomolides, such as serrawettins. These extracellular lipopeptides are described as biocides against many bacteria and fungi and may have a nematicidal activity against phytopathogenic nematodes. Serrawettins W1 and W2 from different strains have [...] Read more.
Serratia strains are ubiquitous microorganisms with the ability to produce serratomolides, such as serrawettins. These extracellular lipopeptides are described as biocides against many bacteria and fungi and may have a nematicidal activity against phytopathogenic nematodes. Serrawettins W1 and W2 from different strains have different structures that might be correlated with distinct genomic organizations. This work used comparative genomics to determine the distribution and the organization of the serrawettins biosynthetic gene clusters in all the 84 publicly available genomes of the Serratia genus. The serrawettin W1 and W2 gene clusters’ organization was established using antiSMASH software and compared with single and short data previously described for YD25TSerratia. Here, the serrawettin W1 gene clusters’ organization is reported for the first time. The serrawettin W1 biosynthetic gene swrW was present in 17 Serratia genomes. Eighty different coding sequence (CDS) were assigned to the W1 gene cluster, 13 being common to all clusters. The serrawettin W2 swrA gene was present in 11 Serratia genomes. The W2 gene clusters included 68 CDS with 24 present in all the clusters. The genomic analysis showed the swrA gene constitutes five modules, four with three domains and one with four domains, while the swrW gene constitutes one module with four domains. This work identified four genes common to all serrawettin gene clusters, highlighting their essential potential in the serrawettins biosynthetic process. Full article
(This article belongs to the Section Genetics and Genomics)
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25 pages, 2484 KiB  
Review
Mitophagy: A New Player in Stem Cell Biology
by George Cairns, Madhavee Thumiah-Mootoo, Yan Burelle and Mireille Khacho
Biology 2020, 9(12), 481; https://doi.org/10.3390/biology9120481 - 19 Dec 2020
Cited by 19 | Viewed by 5308
Abstract
The fundamental importance of functional mitochondria in the survival of most eukaryotic cells, through regulation of bioenergetics, cell death, calcium dynamics and reactive oxygen species (ROS) generation, is undisputed. However, with new avenues of research in stem cell biology these organelles have now [...] Read more.
The fundamental importance of functional mitochondria in the survival of most eukaryotic cells, through regulation of bioenergetics, cell death, calcium dynamics and reactive oxygen species (ROS) generation, is undisputed. However, with new avenues of research in stem cell biology these organelles have now emerged as signaling entities, actively involved in many aspects of stem cell functions, including self-renewal, commitment and differentiation. With this recent knowledge, it becomes evident that regulatory pathways that would ensure the maintenance of mitochondria with state-specific characteristics and the selective removal of organelles with sub-optimal functions must play a pivotal role in stem cells. As such, mitophagy, as an essential mitochondrial quality control mechanism, is beginning to gain appreciation within the stem cell field. Here we review and discuss recent advances in our knowledge pertaining to the roles of mitophagy in stem cell functions and the potential contributions of this specific quality control process on to the progression of aging and diseases. Full article
(This article belongs to the Special Issue Mitophagy Pathways in Health and Disease)
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20 pages, 1508 KiB  
Review
Unravelling the Network of Nuclear Matrix Metalloproteinases for Targeted Drug Design
by Anastasia S. Frolova, Anastasiia I. Petushkova, Vladimir A. Makarov, Surinder M. Soond and Andrey A. Zamyatnin, Jr.
Biology 2020, 9(12), 480; https://doi.org/10.3390/biology9120480 - 19 Dec 2020
Cited by 7 | Viewed by 3467
Abstract
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are responsible for the degradation of a wide range of extracellular matrix proteins, which are involved in many cellular processes to ensure the normal development of tissues and organs. Overexpression of MMPs has been observed to [...] Read more.
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are responsible for the degradation of a wide range of extracellular matrix proteins, which are involved in many cellular processes to ensure the normal development of tissues and organs. Overexpression of MMPs has been observed to facilitate cellular growth, migration, and metastasis of tumor cells during cancer progression. A growing number of these proteins are being found to exist in the nuclei of both healthy and tumor cells, thus highlighting their localization as having a genuine purpose in cellular homeostasis. The mechanism underlying nuclear transport and the effects of MMP nuclear translocation have not yet been fully elucidated. To date, nuclear MMPs appear to have a unique impact on cellular apoptosis and gene regulation, which can have effects on immune response and tumor progression, and thus present themselves as potential therapeutic targets in certain types of cancer or disease. Herein, we highlight and evaluate what progress has been made in this area of research, which clearly has some value as a specific and unique way of targeting the activity of nuclear matrix metalloproteinases within various cell types. Full article
(This article belongs to the Special Issue Proteases—From Basic Structure to Function to Drug Design as Targeted Therapy)
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22 pages, 753 KiB  
Review
The Mitochondrial Proteome of Tumor Cells: A SnapShot on Methodological Approaches and New Biomarkers
by Loredana Moro
Biology 2020, 9(12), 479; https://doi.org/10.3390/biology9120479 - 18 Dec 2020
Cited by 4 | Viewed by 3492
Abstract
Mitochondria are highly dynamic and regulated organelles implicated in a variety of important functions in the cell, including energy production, fatty acid metabolism, iron homeostasis, programmed cell death, and cell signaling. Changes in mitochondrial metabolism, signaling and dynamics are hallmarks of cancer. Understanding [...] Read more.
Mitochondria are highly dynamic and regulated organelles implicated in a variety of important functions in the cell, including energy production, fatty acid metabolism, iron homeostasis, programmed cell death, and cell signaling. Changes in mitochondrial metabolism, signaling and dynamics are hallmarks of cancer. Understanding whether these modifications are associated with alterations of the mitochondrial proteome is particularly relevant from a translational point of view because it may contribute to better understanding the molecular bases of cancer development and progression and may provide new potential prognostic and diagnostic biomarkers as well as novel molecular targets for anti-cancer treatment. Making an inventory of the mitochondrial proteins has been particularly challenging given that there is no unique consensus targeting sequence that directs protein import into mitochondria, some proteins are present at very low levels, while other proteins are expressed only in some cell types, in a particular developmental stage or under specific stress conditions. This review aims at providing the state-of-the-art on methodologies used to characterize the mitochondrial proteome in tumors and highlighting the biological relevance of changes in expression and delocalization of proteins in and out the mitochondria in cancer biology. Full article
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21 pages, 3637 KiB  
Article
Effects of Propranolol on Growth, Lipids and Energy Metabolism and Oxidative Stress Response of Phaeodactylum tricornutum
by Bernardo Duarte, Eduardo Feijão, Ricardo Cruz de Carvalho, Irina A. Duarte, Marisa Silva, Ana Rita Matos, Maria Teresa Cabrita, Sara C. Novais, Marco F. L. Lemos, João Carlos Marques, Isabel Caçador, Patrick Reis-Santos and Vanessa F. Fonseca
Biology 2020, 9(12), 478; https://doi.org/10.3390/biology9120478 - 18 Dec 2020
Cited by 21 | Viewed by 4290
Abstract
Present demographic trends suggest a rise in the contributions of human pharmaceuticals into coastal ecosystems, underpinning an increasing demand to evaluate the ecotoxicological effects and implications of drug residues in marine risk assessments. Propranolol, a non-selective β-adrenoceptor blocker, is used worldwide to treat [...] Read more.
Present demographic trends suggest a rise in the contributions of human pharmaceuticals into coastal ecosystems, underpinning an increasing demand to evaluate the ecotoxicological effects and implications of drug residues in marine risk assessments. Propranolol, a non-selective β-adrenoceptor blocker, is used worldwide to treat high blood pressure conditions and other related cardiovascular conditions. Although diatoms lack β-adrenoceptors, this microalgal group presents receptor-like kinases and proteins with a functional analogy to the animal receptors and that can be targeted by propranolol. In the present work, the authors evaluated the effect of this non-selective β-adrenoceptor blocker in diatom cells using P. tricornutum as a model organism, to evaluate the potential effect of this compound in cell physiology (growth, lipids and energy metabolism and oxidative stress) and its potential relevance for marine ecosystems. Propranolol exposure leads to a significant reduction in diatom cell growth, more evident in the highest concentrations tested. This is likely due to the observed impairment of the main primary photochemistry processes and the enhancement of the mitochondrial respiratory activity. More specifically, propranolol decreased the energy transduction from photosystem II (PSII) to the electron transport chain, leading to an increase in oxidative stress levels. Cells exposed to propranolol also exhibited high-dissipated energy flux, indicating that this excessive energy is efficiently diverted, to some extent, from the photosystems, acting to prevent irreversible photoinhibition. As energy production is impaired at the PSII donor side, preventing energy production through the electron transport chain, diatoms appear to be consuming storage lipids as an energy backup system, to maintain essential cellular functions. This consumption will be attained by an increase in respiratory activity. Considering the primary oxygen production and consumption pathways, propranolol showed a significant reduction of the autotrophic O2 production and an increase in the heterotrophic mitochondrial respiration. Both mechanisms can have negative effects on marine trophic webs, due to a decrease in the energetic input from marine primary producers and a simultaneous oxygen production decrease for heterotrophic species. In ecotoxicological terms, bio-optical and fatty acid data appear as highly efficient tools for ecotoxicity assessment, with an overall high degree of classification when these traits are used to build a toxicological profile, instead of individually assessed. Full article
(This article belongs to the Section Marine Biology)
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21 pages, 2036 KiB  
Article
Epidemic Dynamics via Wavelet Theory and Machine Learning with Applications to Covid-19
by Tô Tat Dat, Protin Frédéric, Nguyen T. T. Hang, Martel Jules, Nguyen Duc Thang, Charles Piffault, Rodríguez Willy, Figueroa Susely, Hông Vân Lê, Wilderich Tuschmann and Nguyen Tien Zung
Biology 2020, 9(12), 477; https://doi.org/10.3390/biology9120477 - 18 Dec 2020
Cited by 11 | Viewed by 4693
Abstract
We introduce the concept of epidemic-fitted wavelets which comprise, in particular, as special cases the number I(t) of infectious individuals at time t in classical SIR models and their derivatives. We present a novel method for modelling epidemic dynamics by [...] Read more.
We introduce the concept of epidemic-fitted wavelets which comprise, in particular, as special cases the number I(t) of infectious individuals at time t in classical SIR models and their derivatives. We present a novel method for modelling epidemic dynamics by a model selection method using wavelet theory and, for its applications, machine learning-based curve fitting techniques. Our universal models are functions that are finite linear combinations of epidemic-fitted wavelets. We apply our method by modelling and forecasting, based on the Johns Hopkins University dataset, the spread of the current Covid-19 (SARS-CoV-2) epidemic in France, Germany, Italy and the Czech Republic, as well as in the US federal states New York and Florida. Full article
(This article belongs to the Special Issue Theories and Models on COVID-19 Epidemics)
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17 pages, 592 KiB  
Review
The Influence of Eggshell on Bone Regeneration in Preclinical In Vivo Studies
by Horia Opris, Cristian Dinu, Mihaela Baciut, Grigore Baciut, Ileana Mitre, Bogdan Crisan, Gabriel Armencea, Daiana Antoaneta Prodan and Simion Bran
Biology 2020, 9(12), 476; https://doi.org/10.3390/biology9120476 - 18 Dec 2020
Cited by 14 | Viewed by 3852
Abstract
The aim of this study is to systemically review the available evidence on the in vivo behavior of eggshell as a guided bone regeneration substitute material. Five databases (PubMed, Cochrane, Web of Science, Scopus, EMBASE) were searched up to October 2020. In vivo [...] Read more.
The aim of this study is to systemically review the available evidence on the in vivo behavior of eggshell as a guided bone regeneration substitute material. Five databases (PubMed, Cochrane, Web of Science, Scopus, EMBASE) were searched up to October 2020. In vivo animal studies with a bone defect model using eggshell as a grafting material were included. Risk of bias was assessed using SYRCLE tool and the quality assessment using the ARRIVE guidelines. Overall, a total of 581 studies were included in the study, 187 after duplicate removal. Using the inclusion and exclusion criteria 167 records were further excluded. The full text of the remaining 20 articles was assessed for eligibility and included in the qualitative and quantitative assessment synthesis. There were different methods of obtaining eggshell grafting materials. Eggshell is a biocompatible grafting material, with osteoconduction proprieties. It forms new bone similar to Bio-Oss and demineralized freeze-dried bone matrix. It can be combined with other materials to enhance its proprieties. Due to the high variability of the procedures, animals, production and assessment methods, no meta-analysis could be performed. Eggshell might be considered a promising biomaterial to be used in bone grafting procedures, though further research is needed. Full article
(This article belongs to the Special Issue Multidisciplinary Insights on Bone Healing)
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22 pages, 5928 KiB  
Article
The Transient Mechanics of Muscle Require Only a Single Force-Producing Cross-Bridge State and a 100 Å Working Stroke
by Carlo Knupp and John M. Squire
Biology 2020, 9(12), 475; https://doi.org/10.3390/biology9120475 - 16 Dec 2020
Cited by 1 | Viewed by 2605
Abstract
An informative probe of myosin cross-bridge behaviour in active muscle is a mechanical transient experiment where, for example, a fully active muscle initially held at constant length is suddenly shortened to a new fixed length, providing a force transient, or has its load [...] Read more.
An informative probe of myosin cross-bridge behaviour in active muscle is a mechanical transient experiment where, for example, a fully active muscle initially held at constant length is suddenly shortened to a new fixed length, providing a force transient, or has its load suddenly reduced, providing a length transient. We describe the simplest cross-bridge mechanical cycle we could find to model these transients. We show using the statistical mechanics of 50,000 cross-bridges that a simple cycle with two actin-attached cross-bridge states, one producing no force and the other producing force, will explain much of what has been observed experimentally, and we discuss the implications of this modelling for our understanding of how muscle works. We show that this same simple model will explain, reasonably well, the isotonic mechanical and X-ray transients under different loads observed by Reconditi et al. (2004, Nature 428, 578) and that there is no need to invoke different cross-bridge step sizes under these different conditions; a step size of 100 Å works well for all loads. We do not claim that this model provides a total mechanical explanation of how muscle works. However, we do suggest that only if there are other observations that cannot be explained by this simple model should something more complicated be considered. Full article
(This article belongs to the Section Biophysics)
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21 pages, 514 KiB  
Review
Lipid Metabolism and Resistance to Anticancer Treatment
by Nicolas Germain, Mélanie Dhayer, Marie Boileau, Quentin Fovez, Jerome Kluza and Philippe Marchetti
Biology 2020, 9(12), 474; https://doi.org/10.3390/biology9120474 - 16 Dec 2020
Cited by 72 | Viewed by 5500
Abstract
Metabolic reprogramming is crucial to respond to cancer cell requirements during tumor development. In the last decade, metabolic alterations have been shown to modulate cancer cells’ sensitivity to chemotherapeutic agents including conventional and targeted therapies. Recently, it became apparent that changes in lipid [...] Read more.
Metabolic reprogramming is crucial to respond to cancer cell requirements during tumor development. In the last decade, metabolic alterations have been shown to modulate cancer cells’ sensitivity to chemotherapeutic agents including conventional and targeted therapies. Recently, it became apparent that changes in lipid metabolism represent important mediators of resistance to anticancer agents. In this review, we highlight changes in lipid metabolism associated with therapy resistance, their significance and how dysregulated lipid metabolism could be exploited to overcome anticancer drug resistance. Full article
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20 pages, 1285 KiB  
Review
Incretin Hormones and Type 2 Diabetes—Mechanistic Insights and Therapeutic Approaches
by Geke Aline Boer and Jens Juul Holst
Biology 2020, 9(12), 473; https://doi.org/10.3390/biology9120473 - 16 Dec 2020
Cited by 68 | Viewed by 14066
Abstract
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is [...] Read more.
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes. Full article
(This article belongs to the Special Issue Mechanistic Insights into the Pathogenesis of Type 2 Diabetes)
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14 pages, 2323 KiB  
Article
Identification of a Novel Thermostable Alkaline Protease from Bacillus megaterium-TK1 for the Detergent and Leather Industry
by Tamilvendan Manavalan, Arulmani Manavalan, Shiyamsundar Ramachandran and Klaus Heese
Biology 2020, 9(12), 472; https://doi.org/10.3390/biology9120472 - 16 Dec 2020
Cited by 26 | Viewed by 4151
Abstract
An increased need by the green industry for enzymes that can be exploited for eco-friendly industrial applications led us to isolate and identify a unique protease obtained from a proteolytic Bacillus megaterium-TK1 strain from a seawater source. The extracellular thermostable serine protease [...] Read more.
An increased need by the green industry for enzymes that can be exploited for eco-friendly industrial applications led us to isolate and identify a unique protease obtained from a proteolytic Bacillus megaterium-TK1 strain from a seawater source. The extracellular thermostable serine protease was processed by multiple chromatography steps. The isolated protease displayed a relative molecular weight (MW) of 33 kDa (confirmed by zymography), optimal enzyme performance at pH 8.0, and maximum enzyme performance at 70 °C with 100% substrate specificity towards casein. The proteolytic action was blocked by phenylmethylsulfonyl fluoride (PMSF), a serine hydrolase inactivator. Protease performance was augmented by several bivalent metal cations. The protease tolerance was studied under stringent conditions with different industrial dispersants and found to be stable with Surf Excel, Tide, or Rin detergents. Moreover, this protease could clean blood-stained fabrics and showed dehairing activity for cow skin with significantly reduced pollution loads. Our results suggest that this serine protease is a promising additive for various eco-friendly usages in both the detergent and leather industries. Full article
(This article belongs to the Section Microbiology)
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18 pages, 4861 KiB  
Article
Different Stages of Alveolar Bone Repair Process Are Compromised in the Type 2 Diabetes Condition: An Experimental Study in Rats
by Letícia Pitol-Palin, Fábio Roberto de Souza Batista, Pedro Henrique Silva Gomes-Ferreira, Gabriel Mulinari-Santos, Edilson Ervolino, Francisley Ávila Souza, Dóris Hissako Matsushita and Roberta Okamoto
Biology 2020, 9(12), 471; https://doi.org/10.3390/biology9120471 - 16 Dec 2020
Cited by 11 | Viewed by 2641
Abstract
The aim of this study was to analyze the stages of the alveolar bone repair in type 2 diabetic rats evaluating the mechanism of mineralization and bone remodeling processes after dental extraction. Forty-eight rats were divided into normoglycemic (NG) and type 2 diabetes [...] Read more.
The aim of this study was to analyze the stages of the alveolar bone repair in type 2 diabetic rats evaluating the mechanism of mineralization and bone remodeling processes after dental extraction. Forty-eight rats were divided into normoglycemic (NG) and type 2 diabetes (T2D) groups. The upper right incisor was extracted and after 3, 7, 14 and 42 days the animals were euthanized. The following analyses were performed: immunolabeling against antibodies TNFα, TGFβ, IL6, WNT, OCN and TRAP, collagen fibers maturation, microtomography and confocal microscopy. Data were submitted to statistical analysis. The immunolabeling analysis showed that the T2D presented a more pronounced alveolar inflammation than NG. Labeling of proteins responsible for bone formation and mineralization was higher in NG than T2D, which presented greater resorptive activity characterized by TRAP labeling. Also, T2D group showed a decrease in the amount of collagen fibers. Micro-CT analysis showed that T2D causes a decrease in bone volume percentage due to deficient trabecular parameters and higher porosity. The T2D bone dynamics show a loss in bone remodeling process. T2D prolongs the local inflammatory process, which impairs the organization and maturation of collagen fibers, delaying bone formation that generates impact on mineralization and bone turnover. Full article
(This article belongs to the Section Cell Biology)
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19 pages, 3503 KiB  
Article
Inhibition of FGF and TGF-β Pathways in hESCs Identify STOX2 as a Novel SMAD2/4 Cofactor
by Peter F. Renz, Daniel Spies, Panagiota Tsikrika, Anton Wutz, Tobias A. Beyer and Constance Ciaudo
Biology 2020, 9(12), 470; https://doi.org/10.3390/biology9120470 - 16 Dec 2020
Cited by 3 | Viewed by 4649
Abstract
The fibroblast growth factor (FGF) and the transforming growth factor-β (TGF-β) pathways are both involved in the maintenance of human embryonic stem cells (hESCs) and regulate the onset of their differentiation. Their converging functions have suggested that these pathways might share a wide [...] Read more.
The fibroblast growth factor (FGF) and the transforming growth factor-β (TGF-β) pathways are both involved in the maintenance of human embryonic stem cells (hESCs) and regulate the onset of their differentiation. Their converging functions have suggested that these pathways might share a wide range of overlapping targets. Published studies have focused on the long-term effects (24–48 h) of FGF and TGF-β inhibition in hESCs, identifying direct and indirect target genes. In this study, we focused on the earliest transcriptome changes occurring between 3 and 9 h after FGF and TGF-β inhibition to identify direct target genes only. Our analysis clearly shows that only a handful of target transcripts are common to both pathways. This is surprising in light of the previous literature, and has implications for models of cell signaling in human pluripotent cells. In addition, we identified STOX2 as a novel primary target of the TGF-β signaling pathway. We show that STOX2 might act as a novel SMAD2/4 cofactor. Taken together, our results provide insights into the effect of cell signaling on the transcription profile of human pluripotent cells Full article
(This article belongs to the Special Issue Pluripotent Stem Cells, Cell Reprogramming and Tissue Modelling)
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12 pages, 2431 KiB  
Article
Evaluation of Metal Tolerance of Fungal Strains Isolated from Contaminated Mining Soil of Nanjing, China
by Fiza Liaquat, Muhammad Farooq Hussain Munis, Urooj Haroon, Samiah Arif, Saddam Saqib, Wajid Zaman, Ali Raza Khan, Jianxin Shi, Shengquan Che and Qunlu Liu
Biology 2020, 9(12), 469; https://doi.org/10.3390/biology9120469 - 15 Dec 2020
Cited by 60 | Viewed by 5588
Abstract
Rapidly increasing industry has resulted in greater discharge of hazardous chemicals in the soil. In the current study, soil samples were collected from Nanjing mine (32°09′19.29″ N 118°56′57.04″ E) and subjected to heavy metal analysis and microbe isolation. A total of 460 fungi [...] Read more.
Rapidly increasing industry has resulted in greater discharge of hazardous chemicals in the soil. In the current study, soil samples were collected from Nanjing mine (32°09′19.29″ N 118°56′57.04″ E) and subjected to heavy metal analysis and microbe isolation. A total of 460 fungi were isolated, and five of these were yeast strains. Most of the strains exhibited tolerance to one metal. Five multimetal tolerant strains were selected and identified as Aspergillus sclerotiorum, Aspergillus aculeatus, Komagataella phaffii, Trichoderma harzianum, and Aspergillus niger. Isolated strains were grown in high concentrations of cadmium (Cd), chromium (Cr) and lead (Pb), for induced-tolerance training. The tolerance index (TI) revealed the highest Cd tolerance of novel K. phaffii strain at 5500 ppm (TI: 0.2). K. phaffii also displayed resistance at 4000 ppm against Cr (TI: 0.32) and Pb (TI: 0.32). In contrast, tolerance training for A. niger was not that successful. K. phaffii also displayed the highest bioaccumulation capacity for Cd (25.23 mg/g), Cu (21.63 mg/g), and Pb (20.63 mg/g) at 200 ppm. Scanning electron microscopy (SEM) explored the morphological changes in the mycelia of stressed fungi. Results of this study describe this delicate approach to be species and metal dependent and suggest a potential utilization of this fungal strain for the bioremediation of contaminated soils. Full article
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25 pages, 5154 KiB  
Article
Time- and Zinc-Related Changes in Biomechanical Properties of Human Colorectal Cancer Cells Examined by Atomic Force Microscopy
by Maria Maares, Claudia Keil, Leif Löher, Andreas Weber, Amsatou Andorfer-Sarr, Hajo Haase, Jagoba Iturri and José L. Toca-Herrera
Biology 2020, 9(12), 468; https://doi.org/10.3390/biology9120468 - 14 Dec 2020
Cited by 2 | Viewed by 3183
Abstract
Monitoring biomechanics of cells or tissue biopsies employing atomic force microscopy (AFM) offers great potential to identify diagnostic biomarkers for diseases, such as colorectal cancer (CRC). Data on the mechanical properties of CRC cells, however, are still scarce. There is strong evidence that [...] Read more.
Monitoring biomechanics of cells or tissue biopsies employing atomic force microscopy (AFM) offers great potential to identify diagnostic biomarkers for diseases, such as colorectal cancer (CRC). Data on the mechanical properties of CRC cells, however, are still scarce. There is strong evidence that the individual zinc status is related to CRC risk. Thus, this study investigates the impact of differing zinc supply on the mechanical response of the in vitro CRC cell lines HT-29 and HT-29-MTX during their early proliferation (24–96 h) by measuring elastic modulus, relaxation behavior, and adhesion factors using AFM. The differing zinc supply severely altered the proliferation of these cells and markedly affected their mechanical properties. Accordingly, zinc deficiency led to softer cells, quantitatively described by 20–30% lower Young’s modulus, which was also reflected by relevant changes in adhesion and rupture event distribution compared to those measured for the respective zinc-adequate cultured cells. These results demonstrate that the nutritional zinc supply severely affects the nanomechanical response of CRC cell lines and highlights the relevance of monitoring the zinc content of cancerous cells or biopsies when studying their biomechanics with AFM in the future. Full article
(This article belongs to the Collection Applied Physics in Cancer Cells)
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11 pages, 1208 KiB  
Article
HLA-DRB1*07:01 and *08:02 Alleles Confer a Protective Effect Against ACPA-Positive Rheumatoid Arthritis in a Latin American Admixed Population
by Patricia Castro-Santos, Jordi Olloquequi, Ricardo A. Verdugo, Miguel A. Gutiérrez, Carmen Pinochet, Luis A. Quiñones and Roberto Díaz-Peña
Biology 2020, 9(12), 467; https://doi.org/10.3390/biology9120467 - 14 Dec 2020
Cited by 8 | Viewed by 2865
Abstract
HLA-DRB1 shared epitope (SE) alleles are important genetic contributors for the risk of developing anti-citrullinated protein antibodies (ACPA)-positive rheumatoid arthritis (RA), particularly in Caucasians. We aimed to analyze the contribution of HLA-DRB1 alleles and single nucleotide polymorphisms (SNPs) within the major histocompatibility complex [...] Read more.
HLA-DRB1 shared epitope (SE) alleles are important genetic contributors for the risk of developing anti-citrullinated protein antibodies (ACPA)-positive rheumatoid arthritis (RA), particularly in Caucasians. We aimed to analyze the contribution of HLA-DRB1 alleles and single nucleotide polymorphisms (SNPs) within the major histocompatibility complex (MHC) region to the susceptibility to develop ACPA-positive RA in a Latin American (LA) population with admixed ancestry. A total of 289 ACPA-positive RA patients and 510 controls were enrolled in this study. The presence of HLA-DRB1*04:01, *09:01 and *10:01 was increased in ACPA-positive RA patients compared with healthy controls (p < 0.0001, p < 0.001 and p < 0.01, respectively), whereas DRB1*07:01 and *08:02 was associated with a decreased risk of ACPA-positive RA (p < 0.001 and p < 0.01, respectively). These results showed a strong correlation with estimates from studies in Asians but not in Caucasian populations. The present study describes the protective effects of the HLA-DRB1*07:01 and *08:02 alleles in ACPA-positive RA patients in a LA population for the first time. Identifying relationships between HLA-DRB1 alleles and RA is important for identifying disease associations in different ethnic groups in order to reach a better understanding of RA worldwide. Full article
(This article belongs to the Section Immunology)
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16 pages, 4758 KiB  
Article
The Cytoplasmic LIM Domain Protein Espinas Contributes to Photoreceptor Layer Selection in the Visual System
by Alejandra Fernández-Pineda, Martí Monge-Asensio, Martín Rios and Marta Morey
Biology 2020, 9(12), 466; https://doi.org/10.3390/biology9120466 - 14 Dec 2020
Viewed by 2494
Abstract
During circuit assembly it is essential that neurons connect with their specific synaptic partners. To facilitate this process, a common strategy in many organisms is the organization of brain regions, including the fly visual system, in layers and columns. The atypical-cadherin Flamingo (Fmi) [...] Read more.
During circuit assembly it is essential that neurons connect with their specific synaptic partners. To facilitate this process, a common strategy in many organisms is the organization of brain regions, including the fly visual system, in layers and columns. The atypical-cadherin Flamingo (Fmi) and the receptor Golden Goal (Gogo) were proposed to regulate both the temporary and final layer selection of the R8 photoreceptor, through the cytoplasmic domain of Gogo. Our data suggests that Fmi intracellular signaling is also relevant for R8 final layer selection. The LIM-domain cytoplasmic molecule Espinas (Esn) binds Fmi, and they cooperatively control dendritic self-avoidance in sensory neurons. We observed defects in R8 layer selection in esn mutants with axons overshooting the final target layer, and we demonstrated that the LIM domain is necessary for layer selection. fmi knockdown in photoreceptors results in most R8 axons stalling at the temporary layer, however, we also detected R8 axons projecting past the final-target layer, and showed that fmi and esn genetically interact. Based on the previously described physical and genetic interactions between Fmi/Esn and the findings presented here, we propose that Esn signals downstream of Fmi to stabilize R8 axons in their final target layer. Full article
(This article belongs to the Section Neuroscience)
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12 pages, 1872 KiB  
Article
Difference between Selenite and Selenate in the Regulation of Growth and Physiological Parameters of Nickel-Exposed Lettuce
by Barbara Hawrylak-Nowak and Renata Matraszek-Gawron
Biology 2020, 9(12), 465; https://doi.org/10.3390/biology9120465 - 12 Dec 2020
Cited by 7 | Viewed by 2564
Abstract
Nickel is an essential plant micronutrient; however, even at low concentrations, it may be phytotoxic. Selenium is a beneficial element with an alleviating effect that has been confirmed in the case of many abiotic stresses, including metal toxicity. The aim of this study [...] Read more.
Nickel is an essential plant micronutrient; however, even at low concentrations, it may be phytotoxic. Selenium is a beneficial element with an alleviating effect that has been confirmed in the case of many abiotic stresses, including metal toxicity. The aim of this study is to assess the effect of two forms of Se (Se(IV) or Se(VI)) on the phytotoxicity, accumulation, and translocation of Ni in lettuce. Nickel causes a reduction in lettuce growth and vitality of roots, probably through increased lipid peroxidation. The application of Se(IV) to a Ni-contaminated medium resulted in a further reduction of growth, especially in the presence of 6 µM Se(IV). The growth-promoting effect of Se was found only in the 2 µM Se(VI)/10 µM Ni treatment. The application of 6 µM Se, regardless of the Se form, to the Ni-containing substrate caused an increase in shoot Ni concentration. In turn, a decrease in root Ni content was found for all Se treatments. The strong aggravation of Ni phytotoxicity in the presence of 6 µM Se(IV) was most likely related to the accumulation of high Se concentration in the roots, and the combination of high root Ni accumulation caused irreversible dysregulation of cell metabolism. Full article
(This article belongs to the Section Plant Science)
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16 pages, 2337 KiB  
Review
The Relationship of the Mechanisms of the Pathogenesis of Multiple Sclerosis and the Expression of Endogenous Retroviruses
by Vera R. Lezhnyova, Ekaterina V. Martynova, Timur I. Khaiboullin, Richard A. Urbanowicz, Svetlana F. Khaiboullina and Albert A. Rizvanov
Biology 2020, 9(12), 464; https://doi.org/10.3390/biology9120464 - 11 Dec 2020
Cited by 7 | Viewed by 3825
Abstract
Two human endogenous retroviruses of the HERV-W family can act as cofactors triggering multiple sclerosis (MS): MS-associated retrovirus (MSRV) and ERVWE1. Endogenous retroviral elements are believed to have integrated in our ancestors’ DNA millions of years ago. Their involvement in the pathogenesis of [...] Read more.
Two human endogenous retroviruses of the HERV-W family can act as cofactors triggering multiple sclerosis (MS): MS-associated retrovirus (MSRV) and ERVWE1. Endogenous retroviral elements are believed to have integrated in our ancestors’ DNA millions of years ago. Their involvement in the pathogenesis of various diseases, including neurodegenerative pathologies, has been demonstrated. Numerous studies have shown a correlation between the deterioration of patients’ health and increased expression of endogenous retroviruses. The exact causes and mechanisms of endogenous retroviruses activation remains unknown, which hampers development of therapeutics. In this review, we will summarize the main characteristics of human endogenous W retroviruses and describe the putative mechanisms of activation, including epigenetic mechanisms, humoral factors as well as the role of the exogenous viral infections. Full article
(This article belongs to the Special Issue Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Applications)
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15 pages, 983 KiB  
Review
Lymphatic Vessels and Their Surroundings: How Local Physical Factors Affect Lymph Flow
by Eleonora Solari, Cristiana Marcozzi, Daniela Negrini and Andrea Moriondo
Biology 2020, 9(12), 463; https://doi.org/10.3390/biology9120463 - 11 Dec 2020
Cited by 36 | Viewed by 8242
Abstract
Lymphatic vessels drain and propel lymph by exploiting external forces that surrounding tissues exert upon vessel walls (extrinsic mechanism) and by using active, rhythmic contractions of lymphatic muscle cells embedded in the vessel wall of collecting lymphatics (intrinsic mechanism). The latter mechanism is [...] Read more.
Lymphatic vessels drain and propel lymph by exploiting external forces that surrounding tissues exert upon vessel walls (extrinsic mechanism) and by using active, rhythmic contractions of lymphatic muscle cells embedded in the vessel wall of collecting lymphatics (intrinsic mechanism). The latter mechanism is the major source of the hydraulic pressure gradient where scant extrinsic forces are generated in the microenvironment surrounding lymphatic vessels. It is mainly involved in generating pressure gradients between the interstitial spaces and the vessel lumen and between adjacent lymphatic vessels segments. Intrinsic pumping can very rapidly adapt to ambient physical stimuli such as hydraulic pressure, lymph flow-derived shear stress, fluid osmolarity, and temperature. This adaptation induces a variable lymph flow, which can precisely follow the local tissue state in terms of fluid and solutes removal. Several cellular systems are known to be sensitive to osmolarity, temperature, stretch, and shear stress, and some of them have been found either in lymphatic endothelial cells or lymphatic muscle. In this review, we will focus on how known physical stimuli affect intrinsic contractility and thus lymph flow and describe the most likely cellular mechanisms that mediate this phenomenon. Full article
(This article belongs to the Section Physiology)
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17 pages, 3444 KiB  
Communication
The Scarcity of Specific Nutrients in Wild Bee Larval Food Negatively Influences Certain Life History Traits
by Zuzanna M. Filipiak and Michał Filipiak
Biology 2020, 9(12), 462; https://doi.org/10.3390/biology9120462 - 11 Dec 2020
Cited by 28 | Viewed by 6251
Abstract
Bee nutrition studies have focused on food quantity rather than quality, and on details of bee biology rather than on the functioning of bees in ecosystems. Ecological stoichiometry has been proposed for studies on bee nutritional ecology as an ecosystem-oriented approach complementary to [...] Read more.
Bee nutrition studies have focused on food quantity rather than quality, and on details of bee biology rather than on the functioning of bees in ecosystems. Ecological stoichiometry has been proposed for studies on bee nutritional ecology as an ecosystem-oriented approach complementary to traditional approaches. It uses atomic ratios of chemical elements in foods and organisms as metrics to ask ecological questions. However, information is needed on the fitness effects of nutritional mismatches between bee demand and the supply of specific elements in food. We performed the first laboratory feeding experiment on the wild bee Osmia bicornis, investigating the impact of Na, K, and Zn scarcity in larval food on fitness-related life history traits (mortality, cocoon development, and imago body mass). We showed that bee fitness is shaped by chemical element availability in larval food; this effect may be sex-specific, where Na might influence female body mass, while Zn influences male mortality and body mass, and the trade-off between K allocation in cocoons and adults may influence cocoon and body development. These results elucidate the nutritional mechanisms underlying the nutritional ecology, behavioral ecology, and population functioning of bees within the context of nutrient cycling in the food web. Full article
(This article belongs to the Section Ecology)
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14 pages, 809 KiB  
Review
Role of BamHI-A Rightward Frame 1 in Epstein–Barr Virus-Associated Epithelial Malignancies
by Rancés Blanco and Francisco Aguayo
Biology 2020, 9(12), 461; https://doi.org/10.3390/biology9120461 - 11 Dec 2020
Cited by 11 | Viewed by 4117
Abstract
Epstein–Barr virus (EBV) infection is associated with a subset of both lymphoid and epithelial malignancies. During the EBV latency program, some viral products involved in the malignant transformation of infected cells are expressed. Among them, the BamHI-A rightward frame 1 (BARF1) is consistently [...] Read more.
Epstein–Barr virus (EBV) infection is associated with a subset of both lymphoid and epithelial malignancies. During the EBV latency program, some viral products involved in the malignant transformation of infected cells are expressed. Among them, the BamHI-A rightward frame 1 (BARF1) is consistently detected in nasopharyngeal carcinomas (NPC) and EBV-associated gastric carcinomas (EBVaGCs) but is practically undetectable in B-cells and lymphomas. Although BARF1 is an early lytic gene, it is expressed during epithelial EBV latency, mainly as a secreted protein (sBARF1). The capacity of sBARF1 to disrupt both innate and adaptive host antiviral immune responses contributes to the immune escape of infected cells. Additionally, BARF1 increases cell proliferation, shows anti-apoptotic effects, and promotes an increased hTERT activity and tumor formation in nude mice cooperating with other host proteins such as c-Myc and H-ras. These facts allow for the consideration of BARF1 as a key protein for promoting EBV-associated epithelial tumors. In this review, we focus on structural and functional aspects of BARF1, such as mechanisms involved in epithelial carcinogenesis and its capacity to modulate the host immune response. Full article
(This article belongs to the Section Microbiology)
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15 pages, 1973 KiB  
Review
Tissue Acidosis Associated with Ischemic Stroke to Guide Neuroprotective Drug Delivery
by Orsolya M. Tóth, Ákos Menyhárt, Rita Frank, Dóra Hantosi, Eszter Farkas and Ferenc Bari
Biology 2020, 9(12), 460; https://doi.org/10.3390/biology9120460 - 11 Dec 2020
Cited by 53 | Viewed by 6643
Abstract
Ischemic stroke is a leading cause of death and disability worldwide. Yet, the effective therapy of focal cerebral ischemia has been an unresolved challenge. We propose here that ischemic tissue acidosis, a sensitive metabolic indicator of injury progression in cerebral ischemia, can be [...] Read more.
Ischemic stroke is a leading cause of death and disability worldwide. Yet, the effective therapy of focal cerebral ischemia has been an unresolved challenge. We propose here that ischemic tissue acidosis, a sensitive metabolic indicator of injury progression in cerebral ischemia, can be harnessed for the targeted delivery of neuroprotective agents. Ischemic tissue acidosis, which represents the accumulation of lactic acid in malperfused brain tissue is significantly exacerbated by the recurrence of spreading depolarizations. Deepening acidosis itself activates specific ion channels to cause neurotoxic cellular Ca2+ accumulation and cytotoxic edema. These processes are thought to contribute to the loss of the ischemic penumbra. The unique metabolic status of the ischemic penumbra has been exploited to identify the penumbra zone with imaging tools. Importantly, acidosis in the ischemic penumbra may also be used to guide therapeutic intervention. Agents with neuroprotective promise are suggested here to be delivered selectively to the ischemic penumbra with pH-responsive smart nanosystems. The administered nanoparticels release their cargo in acidic tissue environment, which reliably delineates sites at risk of injury. Therefore, tissue pH-targeted drug delivery is expected to enrich sites of ongoing injury with the therapeutical agent, without the risk of unfavorable off-target effects. Full article
(This article belongs to the Special Issue Brain Damage and Repair: From Molecular Effects to CNS Disorders)
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20 pages, 2725 KiB  
Article
Impact of Isolation Procedures on the Development of a Preclinical Synovial Fibroblasts/Macrophages in an In Vitro Model of Osteoarthritis
by Cristina Manferdini, Yasmin Saleh, Paolo Dolzani, Elena Gabusi, Diego Trucco, Giuseppe Filardo and Gina Lisignoli
Biology 2020, 9(12), 459; https://doi.org/10.3390/biology9120459 - 10 Dec 2020
Cited by 5 | Viewed by 3967
Abstract
There is a lack ofin vitromodels able to properly represent osteoarthritis (OA) synovial tissue (ST). We aimed to characterize OA ST and to investigate whether a mechanical or enzymatic digestion procedures influence synovial cell functional heterogeneity in vitro. Procedures using mechanical nondigested fragments [...] Read more.
There is a lack ofin vitromodels able to properly represent osteoarthritis (OA) synovial tissue (ST). We aimed to characterize OA ST and to investigate whether a mechanical or enzymatic digestion procedures influence synovial cell functional heterogeneity in vitro. Procedures using mechanical nondigested fragments (NDF), synovial digested fragments (SDF), and filtrated synovial digested cells (SDC) were compared. An immunophenotypic profile was performed to distinguish synovial fibroblasts (CD55, CD73, CD90, CD106), macrophages (CD14, CD68), M1-like (CD80, CD86), and M2-like (CD163, CD206) synovial macrophages. Pro-inflammatory (interleukin 6 IL6), tumor necrosis factor alpha (TNFα), chemokine C-C motif ligand 3 (CCL3/MIP1α), C-X- motif chemokine ligand 10 (CXCL10/IP10) and anti-inflammatory (interleukin 10 (IL10)), transforming growth factor beta 1 (TGFβ1), C-C motif chemokine ligand 18 (CCL18) cytokines were evaluated. CD68 and CD163 markers were higher in NDF and SDF compared to the SDC procedure, while CD80, CD86, and CD206 were higher only in NDF compared to the SDC procedure. Synovial fibroblast markers showed similar percentages. TNFα, CCL3/MIP1α, CXCL10/IP10, and CCL18 were higher in NDF compared to SDC, but not compared to SDF. IL10 and TGFβ1 were higher in NDF than SDC at the molecular level, while IL6 did not show differences among procedures. We demonstrated that NDF isolation procedures better preserved the heterogeneity of specific OA synovial populations (fibroblasts, macrophages), fostering their use for testing new cell therapies or drugs for OA, reducing or avoiding the use of animal models. Full article
(This article belongs to the Special Issue Biology of Osteoarthritis)
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14 pages, 1381 KiB  
Review
Discoveries for Long Non-Coding RNA Dynamics in Traumatic Brain Injury
by Key-Hwan Lim, Sumin Yang, Sung-Hyun Kim, Sungkun Chun and Jae-Yeol Joo
Biology 2020, 9(12), 458; https://doi.org/10.3390/biology9120458 - 10 Dec 2020
Cited by 10 | Viewed by 2996
Abstract
In recent years, our understanding of long non-coding RNAs (lncRNAs) has been challenged with advances in genome sequencing and the widespread use of high-throughput analysis for identifying novel lncRNAs. Since then, the characterization of lncRNAs has contributed to the establishment of their molecular [...] Read more.
In recent years, our understanding of long non-coding RNAs (lncRNAs) has been challenged with advances in genome sequencing and the widespread use of high-throughput analysis for identifying novel lncRNAs. Since then, the characterization of lncRNAs has contributed to the establishment of their molecular roles and functions in transcriptional regulation. Although genetic studies have so far explored the sequence-based primary function of lncRNAs that guides the expression of target genes, recent insights have shed light on the potential of lncRNAs for widening the identification of biomarkers from non-degenerative to neurodegenerative diseases. Therefore, further advances in the genetic characteristics of lncRNAs are expected to lead to diagnostic accuracy during disease progression. In this review, we summarized the latest studies of lncRNAs in TBI as a non-degenerative disease and discussed their potential limitations for clinical treatment. Full article
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15 pages, 491 KiB  
Review
Apoptosis of Eosinophil Granulocytes
by Martina Zustakova, Lucie Kratochvilova and Petr Slama
Biology 2020, 9(12), 457; https://doi.org/10.3390/biology9120457 - 10 Dec 2020
Cited by 5 | Viewed by 3186
Abstract
In the past 10 years, the number of people in the Czech Republic with allergies has doubled to over three million. Allergic pollen catarrh, constitutional dermatitis and asthma are the allergic disorders most often diagnosed. Genuine food allergies today affect 6–8% of nursing [...] Read more.
In the past 10 years, the number of people in the Czech Republic with allergies has doubled to over three million. Allergic pollen catarrh, constitutional dermatitis and asthma are the allergic disorders most often diagnosed. Genuine food allergies today affect 6–8% of nursing infants, 3–5% of small children, and 2–4% of adults. These disorders are connected with eosinophil granulocytes and their apoptosis. Eosinophil granulocytes are postmitotic leukocytes containing a number of histotoxic substances that contribute to the initiation and continuation of allergic inflammatory reactions. Eosinophilia results from the disruption of the standard half-life of eosinophils by the expression of mechanisms that block the apoptosis of eosinophils, leading to the development of chronic inflammation. Glucocorticoids are used as a strong acting anti-inflammatory medicine in the treatment of hypereosinophilia. The removal of eosinophils by the mechanism of apoptosis is the effect of this process. This work sums up the contemporary knowledge concerning the apoptosis of eosinophils, its role in the aforementioned disorders, and the indications for the use of glucocorticoids in their related therapies. Full article
(This article belongs to the Section Cell Biology)
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