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Biology, Volume 9, Issue 6 (June 2020) – 30 articles

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Cover Story (view full-size image) Invertebrates show more variation in muscle organization than vertebrates. The Procambarus clarkii [...] Read more.
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Open AccessReview
Lessons from SARS-CoV-2 Pandemic: Evolution, Disease Dynamics and Future
Biology 2020, 9(6), 141; https://doi.org/10.3390/biology9060141 - 26 Jun 2020
Viewed by 448
Abstract
The COVID-19 pandemic is rising at an unprecedented rate. The surging number of deaths every day, global lockdown and travel restrictions have resulted in huge losses to society. The impact is massive and will leave a historical footprint. The Spanish Flu of 1918, [...] Read more.
The COVID-19 pandemic is rising at an unprecedented rate. The surging number of deaths every day, global lockdown and travel restrictions have resulted in huge losses to society. The impact is massive and will leave a historical footprint. The Spanish Flu of 1918, which was the last pandemic that had a similar impact, was shadowed under the consequences of World War I. All the brilliance, strength and economies of countries worldwide are aimed at fighting the COVID-19 pandemic. The knowledge about coronavirus dynamics, its nature and epidemiology are expanding every day. The present review aims to summarize the structure, epidemiology, symptoms, statistical status of the disease status, intervention strategies and deliberates the lessons learnt during the pandemic. The intervention approaches, antiviral drug repurposing and vaccine trials are intensified now. Statistical interpretations of disease dynamics and their projections may help the decision-makers. Full article
(This article belongs to the Section Microbiology)
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Open AccessReview
Mass Spectrometry to Study Chromatin Compaction
Biology 2020, 9(6), 140; https://doi.org/10.3390/biology9060140 - 26 Jun 2020
Viewed by 412
Abstract
Chromatin accessibility is a major regulator of gene expression. Histone writers/erasers have a critical role in chromatin compaction, as they “flag” chromatin regions by catalyzing/removing covalent post-translational modifications on histone proteins. Anomalous chromatin decondensation is a common phenomenon in cells experiencing aging and [...] Read more.
Chromatin accessibility is a major regulator of gene expression. Histone writers/erasers have a critical role in chromatin compaction, as they “flag” chromatin regions by catalyzing/removing covalent post-translational modifications on histone proteins. Anomalous chromatin decondensation is a common phenomenon in cells experiencing aging and viral infection. Moreover, about 50% of cancers have mutations in enzymes regulating chromatin state. Numerous genomics methods have evolved to characterize chromatin state, but the analysis of (in)accessible chromatin from the protein perspective is not yet in the spotlight. We present an overview of the most used approaches to generate data on chromatin accessibility and then focus on emerging methods that utilize mass spectrometry to quantify the accessibility of histones and the rest of the chromatin bound proteome. Mass spectrometry is currently the method of choice to quantify entire proteomes in an unbiased large-scale manner; accessibility on chromatin of proteins and protein modifications adds an extra quantitative layer to proteomics dataset that assist more informed data-driven hypotheses in chromatin biology. We speculate that this emerging new set of methods will enhance predictive strength on which proteins and histone modifications are critical in gene regulation, and which proteins occupy different chromatin states in health and disease. Full article
(This article belongs to the Special Issue Chromatin Dynamics)
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Open AccessArticle
Spectral Distribution of Ultra-Weak Photon Emission as a Response to Wounding in Plants: An In Vivo Study
Biology 2020, 9(6), 139; https://doi.org/10.3390/biology9060139 - 26 Jun 2020
Viewed by 231
Abstract
It is well established that every living organism spontaneously emits photons referred to as ultra-weak photon emission (synonym biophotons or low-level chemiluminescence) which inherently embodies information about the wellbeing of the source. In recent years, efforts have been made to use this feature [...] Read more.
It is well established that every living organism spontaneously emits photons referred to as ultra-weak photon emission (synonym biophotons or low-level chemiluminescence) which inherently embodies information about the wellbeing of the source. In recent years, efforts have been made to use this feature as a non-invasive diagnostic tool related to the detection of food quality, agriculture and biomedicine. The current study deals with stress resulting from wounding (mechanical injury) on Arabidopsis thaliana and how it modifies the spontaneous ultra-weak photon emission. The ultra-weak photon emission from control (non-wounded) and stressed (wounded) plants was monitored using different modes of ultra-weak photon emission measurement sensors like charge-coupled device (CCD) cameras and photomultiplier tubes (PMT) and the collected data were analyzed to determine the level of stress generated, photon emission patterns, and underlying biochemical process. It is generally considered that electronically excited species formed during the oxidative metabolic processes are responsible for the ultra-weak photon emission. In the current study, a high-performance cryogenic full-frame CCD camera was employed for two-dimensional in-vivo imaging of ultra-weak photon emission (up to several counts/s) and the spectral analysis was done by using spectral system connected to a PMT. The results show that Arabidopsis subjected to mechanical injury enhances the photon emission and also leads to changes in the spectral pattern of ultra-weak photon emission. Thus, ultra-weak photon emission can be used as a tool for oxidative stress imaging and can pave its way into numerous plant application research. Full article
(This article belongs to the Section Plant Science)
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Open AccessArticle
Kinematic Sub-Populations in Bull Spermatozoa: A Comparison of Classical and Bayesian Approaches
Biology 2020, 9(6), 138; https://doi.org/10.3390/biology9060138 - 26 Jun 2020
Viewed by 438
Abstract
The ejaculate is heterogenous and sperm sub-populations with different kinematic patterns can be identified in various species. Nevertheless, although these sub-populations are statistically well defined, the statistical differences are not always relevant. The aim of the present study was to characterize kinematic sub-populations [...] Read more.
The ejaculate is heterogenous and sperm sub-populations with different kinematic patterns can be identified in various species. Nevertheless, although these sub-populations are statistically well defined, the statistical differences are not always relevant. The aim of the present study was to characterize kinematic sub-populations in sperm from two bovine species, and diluted with different commercial extenders, and to determine the statistical relevance of sub-populations through Bayesian analysis. Semen from 10 bulls was evaluated after thawing. An ISAS®v1 computer-assisted sperm analysis (CASA)-Mot system was employed with an image acquisition rate of 50 Hz and ISAS®D4C20 counting chambers. Sub-populations of motile spermatozoa were characterized using multivariate procedures such as principal components (PCs) analysis and clustering methods (k-means model). Four different sperm sub-populations were identified from three PCs that involved progressiveness, velocity, and cell undulatory movement. The proportions of the different sperm sub-populations varied with the extender used and in the two species. Despite a statistical difference (p < 0.05) between extenders, the Bayesian analysis confirmed that only one of them (Triladyl®) presented relevant differences in kinematic patterns when compared with Tris-EY and OptiXcell®. Extenders differed in the proportion of sperm cells in each of the kinematic sub-populations. Similar patterns were identified in Bos taurus and Bos indicus. Bayesian results indicate that sub-populations SP1, SP2, and SP3 were different for PC criteria and these differences were relevant. For velocity, linearity, and progressiveness, the SP4 did not show a relevant difference regarding the other sperm sub-populations. The classical approach of clustering or sperm subpopulation thus may not have a direct biological meaning. Therefore, the biological relevance of sperm sub-populations needs to be reevaluated. Full article
(This article belongs to the Special Issue Factors Affecting In Vitro Assessment of Sperm Quality)
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Open AccessReview
The Role of Mitochondria in Cardiovascular Diseases
Biology 2020, 9(6), 137; https://doi.org/10.3390/biology9060137 - 25 Jun 2020
Viewed by 258
Abstract
The role of mitochondria in cardiovascular diseases is receiving ever growing attention. As a central player in the regulation of cellular metabolism and a powerful controller of cellular fate, mitochondria appear to comprise an interesting potential therapeutic target. With the development of DNA [...] Read more.
The role of mitochondria in cardiovascular diseases is receiving ever growing attention. As a central player in the regulation of cellular metabolism and a powerful controller of cellular fate, mitochondria appear to comprise an interesting potential therapeutic target. With the development of DNA sequencing methods, mutations in mitochondrial DNA (mtDNA) became a subject of intensive study, since many directly lead to mitochondrial dysfunction, oxidative stress, deficient energy production and, as a result, cell dysfunction and death. Many mtDNA mutations were found to be associated with chronic human diseases, including cardiovascular disorders. In particular, 17 mtDNA mutations were reported to be associated with ischemic heart disease in humans. In this review, we discuss the involvement of mitochondrial dysfunction in the pathogenesis of atherosclerosis and describe the mtDNA mutations identified so far that are associated with atherosclerosis and its risk factors. Full article
(This article belongs to the Section Cell Biology)
Open AccessArticle
Termite Societies Promote the Taxonomic and Functional Diversity of Archaeal Communities in Mound Soils
Biology 2020, 9(6), 136; https://doi.org/10.3390/biology9060136 - 25 Jun 2020
Viewed by 266
Abstract
Recent studies involving microbial communities in termite mounds have been more focused on bacteria and fungi with little attention given to archaea, which play significant roles in nutrient cycling. Thus, we aimed at characterizing the archaeal taxonomic and functional diversity in two termite [...] Read more.
Recent studies involving microbial communities in termite mounds have been more focused on bacteria and fungi with little attention given to archaea, which play significant roles in nutrient cycling. Thus, we aimed at characterizing the archaeal taxonomic and functional diversity in two termite mound soils using the shotgun sequencing method with the assumption that termite activities could promote archaeal diversity. Our findings showed that termite mound soils have archaeal groups that are taxonomically different from their surrounding soils, with Euryarchaeota, Korarchaeota, and Nanoarchaeota being predominant while Thaumarchaeota and Crenarchaeota were predominant in the surrounding soils. Additionally, the observed nutrient pathways: phosphorus, nitrogen, and sulfur were all significantly more predominant in termite mound soils than in their comparative surrounding soils. Alpha diversity showed that archaea were not significantly different within termite mound soils and the surrounding soils. The beta diversity revealed significant differences in the archaeal taxonomic composition and their functional categories between the termite mounds and surrounding soils. Our canonical correspondence analysis revealed that the distribution of archaeal communities was likely dependent on the soil properties. Our results suggested that termite activities may promote the diversity of archaea; with some of our sequences grouped as unclassified archaea, there is a need for further research to unveil their identity. Full article
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Open AccessArticle
On a Coupled Time-Dependent SIR Models Fitting with New York and New-Jersey States COVID-19 Data
Biology 2020, 9(6), 135; https://doi.org/10.3390/biology9060135 - 24 Jun 2020
Viewed by 266
Abstract
This article describes a simple Susceptible Infected Recovered (SIR) model fitting with COVID-19 data for the month of March 2020 in New York (NY) state. The model is a classical SIR, but is non-autonomous; the rate of susceptible people becoming infected is adjusted [...] Read more.
This article describes a simple Susceptible Infected Recovered (SIR) model fitting with COVID-19 data for the month of March 2020 in New York (NY) state. The model is a classical SIR, but is non-autonomous; the rate of susceptible people becoming infected is adjusted over time in order to fit the available data. The death rate is also secondarily adjusted. Our fitting is made under the assumption that due to limiting number of tests, a large part of the infected population has not been tested positive. In the last part, we extend the model to take into account the daily fluxes between New Jersey (NJ) and NY states and fit the data for both states. Our simple model fits the available data, and illustrates typical dynamics of the disease: exponential increase, apex and decrease. The model highlights a decrease in the transmission rate over the period which gives a quantitative illustration about how lockdown policies reduce the spread of the pandemic. The coupled model with NY and NJ states shows a wave in NJ following the NY wave, illustrating the mechanism of spread from one attractive hot spot to its neighbor. Full article
(This article belongs to the Special Issue Theories and Models on COVID-19 Epidemics)
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Open AccessArticle
A Brief Theory of Epidemic Kinetics
Biology 2020, 9(6), 134; https://doi.org/10.3390/biology9060134 - 22 Jun 2020
Viewed by 347
Abstract
In the context of the COVID-19 epidemic, and on the basis of the Theory of Dynamical Systems, we propose a simple theoretical approach for the expansion of contagious diseases, with a particular focus on viral respiratory tracts. The infection develops through contacts between [...] Read more.
In the context of the COVID-19 epidemic, and on the basis of the Theory of Dynamical Systems, we propose a simple theoretical approach for the expansion of contagious diseases, with a particular focus on viral respiratory tracts. The infection develops through contacts between contagious and exposed people, with a rate proportional to the number of contagious and of non-immune individuals, to contact duration and turnover, inversely proportional to the efficiency of protection measures, and balanced by the average individual recovery response. The obvious initial exponential increase is readily hindered by the growing recovery rate, and also by the size reduction of the exposed population. The system converges towards a stable attractor whose value is expressed in terms of the “reproductive rate” R0, depending on contamination and recovery factors. Various properties of the attractor are examined, and particularly its relations with R0. Decreasing this ratio below a critical value leads to a tipping threshold beyond which the epidemic is over. By contrast, significant values of the above ratio may bring the system through a bifurcating hierarchy of stable cycles up to a chaotic behaviour. Full article
(This article belongs to the Special Issue Theories and Models on COVID-19 Epidemics)
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Open AccessArticle
Laboratory Diagnostics of Rickettsia Infections in Denmark 2008–2015
Biology 2020, 9(6), 133; https://doi.org/10.3390/biology9060133 - 19 Jun 2020
Viewed by 365
Abstract
Rickettsiosis is a vector-borne disease caused by bacterial species in the genus Rickettsia. Ticks in Scandinavia are reported to be infected with Rickettsia, yet only a few Scandinavian human cases are described, and rickettsiosis is poorly understood. The aim of this [...] Read more.
Rickettsiosis is a vector-borne disease caused by bacterial species in the genus Rickettsia. Ticks in Scandinavia are reported to be infected with Rickettsia, yet only a few Scandinavian human cases are described, and rickettsiosis is poorly understood. The aim of this study was to determine the prevalence of rickettsiosis in Denmark based on laboratory findings. We found that in the Danish individuals who tested positive for Rickettsia by serology, the majority (86%; 484/561) of the infections belonged to the spotted fever group. In contrast, we could confirm 13 of 41 (32%) PCR-positive individuals by sequencing and identified all of these as R. africae, indicating infections after travel exposure. These 13 samples were collected from wound/skin material. In Denmark, approximately 85 individuals test positive for Rickettsia spp. annually, giving an estimated 26% (561/2147) annual prevalence among those suspected of rickettsiosis after tick bites. However, without clinical data and a history of travel exposure, a true estimation of rickettsiosis acquired endemically by tick bites cannot be made. Therefore, we recommend that both clinical data and specific travel exposure be included in a surveillance system of Rickettsia infections. Full article
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Open AccessArticle
Unreported Cases for Age Dependent COVID-19 Outbreak in Japan
Biology 2020, 9(6), 132; https://doi.org/10.3390/biology9060132 - 17 Jun 2020
Viewed by 417
Abstract
We investigate the age structured data for the COVID-19 outbreak in Japan. We consider a mathematical model for the epidemic with unreported infectious patient with and without age structure. In particular, we build a new mathematical model and a new computational method to [...] Read more.
We investigate the age structured data for the COVID-19 outbreak in Japan. We consider a mathematical model for the epidemic with unreported infectious patient with and without age structure. In particular, we build a new mathematical model and a new computational method to fit the data by using age classes dependent exponential growth at the early stage of the epidemic. This allows to take into account differences in the response of patients to the disease according to their age. This model also allows for a heterogeneous response of the population to the social distancing measures taken by the local government. We fit this model to the observed data and obtain a snapshot of the effective transmissions occurring inside the population at different times, which indicates where and among whom the disease propagates after the start of public mitigation measures. Full article
(This article belongs to the Special Issue Theories and Models on COVID-19 Epidemics)
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Open AccessArticle
Oral Microbiota and Immune System Crosstalk: A Translational Research
Biology 2020, 9(6), 131; https://doi.org/10.3390/biology9060131 - 16 Jun 2020
Viewed by 391
Abstract
Background: Oral pathogens may exert the ability to trigger differently the activation of local macrophage immune responses, for instance Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans induce predominantly pro-inflammatory (M1-like phenotypes) responses, while oral commensal microbiota primarily elicits macrophage functions consistent with the anti-inflammatory (M2-like [...] Read more.
Background: Oral pathogens may exert the ability to trigger differently the activation of local macrophage immune responses, for instance Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans induce predominantly pro-inflammatory (M1-like phenotypes) responses, while oral commensal microbiota primarily elicits macrophage functions consistent with the anti-inflammatory (M2-like phenotypes). Methods: In healthy individuals vs. periodontal disease patients’ blood samples, the differentiation process from monocyte to M1 and M2 was conducted using two typical growth factors, the granulocyte/macrophage colony stimulating factor (GM-CSF) and the macrophage colony stimulating factor (M-CSF). Results: In contrast with the current literature our outcomes showed a noticeable increase of macrophage polarization from healthy individuals vs. periodontal patients. The biological and clinical significance of these data was discussed. Conclusions: Our translational findings showed a significant variance between control versus periodontal disease groups in M1 and M2 marker expression within the second group significantly lower skews differentiation of M2-like macrophages towards an M1-like phenotype. Macrophage polarization in periodontal tissue may be responsible for the development and progression of inflammation-induced periodontal tissue damage, including alveolar bone loss, and modulating macrophage function may be a potential strategy for periodontal disease management. Full article
(This article belongs to the Special Issue Microbiota and Immune System Crosstalk 2020)
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Open AccessArticle
Norpa Signalling and the Seasonal Circadian Locomotor Phenotype in Drosophila
Biology 2020, 9(6), 130; https://doi.org/10.3390/biology9060130 - 16 Jun 2020
Viewed by 308
Abstract
In this paper, we review the role of the norpA-encoded phospholipase C in light and thermal entrainment of the circadian clock in Drosophila melanogaster. We extend our discussion to the role of norpA in the thermo-sensitive splicing of the per 3′ UTR [...] Read more.
In this paper, we review the role of the norpA-encoded phospholipase C in light and thermal entrainment of the circadian clock in Drosophila melanogaster. We extend our discussion to the role of norpA in the thermo-sensitive splicing of the per 3′ UTR, which has significant implications for seasonal adaptations of circadian behaviour. We use the norpA mutant-generated enhancement of per splicing and the corresponding advance that it produces in the morning (M) and evening (E) locomotor component to dissect out the neurons that are contributing to this norpA phenotype using GAL4/UAS. We initially confirmed, by immunocytochemistry and in situ hybridisation in adult brains, that norpA expression is mostly concentrated in the eyes, but we were unable to unequivocally reveal norpA expression in the canonical clock cells using these methods. In larval brains, we did see some evidence for co-expression of NORPA with PDF in clock neurons. Nevertheless, downregulation of norpA in clock neurons did generate behavioural advances in adults, with the eyes playing a significant role in the norpA seasonal phenotype at high temperatures, whereas the more dorsally located CRYPTOCHROME-positive clock neurons are the likely candidates for generating the norpA behavioural effects in the cold. We further show that knockdown of the related plc21C encoded phospholipase in clock neurons does not alter per splicing nor generate any of the behavioural advances seen with norpA. Our results with downregulating norpA and plc21C implicate the rhodopsins Rh2/Rh3/Rh4 in the eyes as mediating per 3′ UTR splicing at higher temperatures and indicate that the CRY-positive LNds, also known as ‘evening’ cells are likely mediating the low-temperature seasonal effects on behaviour via altering per 3′UTR splicing. Full article
(This article belongs to the Special Issue Biological Clocks)
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Open AccessReview
Evolution of Allorecognition in the Tunicata
Biology 2020, 9(6), 129; https://doi.org/10.3390/biology9060129 - 16 Jun 2020
Viewed by 285
Abstract
Allorecognition, the ability to distinguish self or kin from unrelated conspecifics, plays several important biological roles in invertebrate animals. Two of these roles include negotiating limited benthic space for colonial invertebrates, and inbreeding avoidance through self-incompatibility systems. Subphylum Tunicata (Phylum Chordata), the sister [...] Read more.
Allorecognition, the ability to distinguish self or kin from unrelated conspecifics, plays several important biological roles in invertebrate animals. Two of these roles include negotiating limited benthic space for colonial invertebrates, and inbreeding avoidance through self-incompatibility systems. Subphylum Tunicata (Phylum Chordata), the sister group to the vertebrates, is a promising group in which to study allorecognition. Coloniality has evolved many times independently in the tunicates, and the best known invertebrate self-incompatibility systems are in tunicates. Recent phylogenomic studies have coalesced around a phylogeny of the Tunicata as well as the Order Stolidobranchia within the Tunicata, providing a path forward for the study of allorecognition in this group. Full article
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Open AccessLetter
COVID-19 Infection Fatality Rate Associated with Incidence—A Population-Level Analysis of 19 Spanish Autonomous Communities
Biology 2020, 9(6), 128; https://doi.org/10.3390/biology9060128 - 16 Jun 2020
Viewed by 828
Abstract
Previous studies have found large variations in the COVID-19 infection fatality rate (IFR). This study hypothesized that IFR would be influenced by COVID-19 epidemic intensity. We tested the association between epidemic intensity and IFR using serological results from a recent large SARS-CoV-2 serosurvey [...] Read more.
Previous studies have found large variations in the COVID-19 infection fatality rate (IFR). This study hypothesized that IFR would be influenced by COVID-19 epidemic intensity. We tested the association between epidemic intensity and IFR using serological results from a recent large SARS-CoV-2 serosurvey (N = 60,983) in 19 Spanish regions. The infection fatality rate for Spain as a whole was 1.15% and varied between 0.13% and 3.25% in the regions (median 1.07%, IQR 0.69–1.32%). The IFR by region was positively associated with SARS-CoV-2 seroprevalence (rho = 0.54; p = 0.0162), cases/100,000 (rho = 0.75; p = 0.002), hospitalizations/100,000 (rho = 0.78; p = 0.0001), mortality/100,000 (rho = 0.77; p = 0.0001) and case fatality rate (rho = 0.49; p = 0.0327). These results suggest that the SARS-CoV-2 IFR is not fixed. The Spanish regions with more rapid and extensive spread of SARS-CoV-2 had higher IFRs. These findings are compatible with the theory that slowing the spread of COVID-19 down reduces the IFR and case fatality rate via preventing hospitals from being overrun, and thus allowing better and lifesaving care. Full article
(This article belongs to the Section Evolutionary Biology)
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Open AccessArticle
Lymphoid Tissue in Teleost Gills: Variations on a Theme
Biology 2020, 9(6), 127; https://doi.org/10.3390/biology9060127 - 15 Jun 2020
Viewed by 387
Abstract
In bony fish, the gill filaments are essential for gas exchanges, but also are vulnerable to infection by water-borne microorganisms. Omnipresent across fish, gill-associated lymphoid tissues (GIALT) regulate interactions with local microbiota and halt infection by pathogens. A special GIALT structure has recently [...] Read more.
In bony fish, the gill filaments are essential for gas exchanges, but also are vulnerable to infection by water-borne microorganisms. Omnipresent across fish, gill-associated lymphoid tissues (GIALT) regulate interactions with local microbiota and halt infection by pathogens. A special GIALT structure has recently been found in Salmonids, the interbranchial lymphoid tissue (ILT). However, the structural variation of GIALT across bony fish remains largely unknown. Here, we show how this critical zone of interaction evolved across fishes. By labeling a conserved T-cell epitope on tissue sections, we find that several basal groups of teleosts possess typical ILT, while modern teleosts have lymphoepithelium of different shape and size at the base of primary gill filaments. Within Cypriniformes, neither body size variation between two related species, zebrafish and common carp, nor morphotype variation, did have a drastic effect on the structure of ILT. Thereby this study is the first to describe the presence of ILT in zebrafish. The ILT variability across fish orders seems to represent different evolutionary solutions to balancing trade-offs between multiple adaptations of jaws and pharyngeal region, and immune responses. Our data point to a wide structural variation in gill immunity between basal groups and modern teleosts. Full article
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Open AccessReview
STAT3 Pathway in Gastric Cancer: Signaling, Therapeutic Targeting and Future Prospects
Biology 2020, 9(6), 126; https://doi.org/10.3390/biology9060126 - 12 Jun 2020
Viewed by 446
Abstract
Molecular signaling pathways play a significant role in the regulation of biological mechanisms, and their abnormal expression can provide the conditions for cancer development. The signal transducer and activator of transcription 3 (STAT3) is a key member of the STAT proteins and its [...] Read more.
Molecular signaling pathways play a significant role in the regulation of biological mechanisms, and their abnormal expression can provide the conditions for cancer development. The signal transducer and activator of transcription 3 (STAT3) is a key member of the STAT proteins and its oncogene role in cancer has been shown. STAT3 is able to promote the proliferation and invasion of cancer cells and induces chemoresistance. Different downstream targets of STAT3 have been identified in cancer and it has also been shown that microRNA (miR), long non-coding RNA (lncRNA) and other molecular pathways are able to function as upstream mediators of STAT3 in cancer. In the present review, we focus on the role and regulation of STAT3 in gastric cancer (GC). miRs and lncRNAs are considered as potential upstream mediators of STAT3 and they are able to affect STAT3 expression in exerting their oncogene or onco-suppressor role in GC cells. Anti-tumor compounds suppress the STAT3 signaling pathway to restrict the proliferation and malignant behavior of GC cells. Other molecular pathways, such as sirtuin, stathmin and so on, can act as upstream mediators of STAT3 in GC. Notably, the components of the tumor microenvironment that are capable of targeting STAT3 in GC, such as fibroblasts and macrophages, are discussed in this review. Finally, we demonstrate that STAT3 can target oncogene factors to enhance the proliferation and metastasis of GC cells. Full article
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Open AccessArticle
Phosphoinositide Lipids in Ocular Tissues
Biology 2020, 9(6), 125; https://doi.org/10.3390/biology9060125 - 12 Jun 2020
Viewed by 313
Abstract
Inositol phospholipids play an important role in cell physiology. The inositol head groups are reversibly phosphorylated to produce seven distinct phosphorylated inositides, commonly referred to as phosphoinositides (PIs). These seven PIs are dynamically interconverted from one PI to another by the action of [...] Read more.
Inositol phospholipids play an important role in cell physiology. The inositol head groups are reversibly phosphorylated to produce seven distinct phosphorylated inositides, commonly referred to as phosphoinositides (PIs). These seven PIs are dynamically interconverted from one PI to another by the action of PI kinases and PI phosphatases. The PI signals regulate a wide variety of cellular functions, including organelle distinction, vesicular transport, cytoskeletal organization, nuclear events, regulation of ion channels, cell signaling, and host–pathogen interactions. Most of the studies of PIs in ocular tissues are based on the PI enzymes and PI phosphatases. In this study, we examined the PI levels in the cornea, retinal pigment epithelium (RPE), and retina using PI-binding protein as probes. We have examined the lipids PI(3)P, PI(4)P, PI(3,4)P2, PI(4,5)P2, and PI(3,4,5)P3, and each is present in the cornea, RPE, and retina. Alterations in the levels of these PIs in mouse models of retinal disease and corneal infections have been reported, and the results of our study will help in the management of anomalous phosphoinositide metabolism in ocular tissues. Full article
(This article belongs to the Section Cell Biology)
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Open AccessReview
Soluble Epoxide Hydrolase Inhibition in Liver Diseases: A Review of Current Research and Knowledge Gaps
Biology 2020, 9(6), 124; https://doi.org/10.3390/biology9060124 - 12 Jun 2020
Viewed by 401
Abstract
Emerging evidence suggests that soluble epoxide hydrolase (sEH) inhibition is a valuable therapeutic strategy for the treatment of numerous diseases, including those of the liver. sEH rapidly degrades cytochrome P450-produced epoxygenated lipids (epoxy-fatty acids), which are synthesized from omega-3 and omega-6 polyunsaturated fatty [...] Read more.
Emerging evidence suggests that soluble epoxide hydrolase (sEH) inhibition is a valuable therapeutic strategy for the treatment of numerous diseases, including those of the liver. sEH rapidly degrades cytochrome P450-produced epoxygenated lipids (epoxy-fatty acids), which are synthesized from omega-3 and omega-6 polyunsaturated fatty acids, that generally exert beneficial effects on several cellular processes. sEH hydrolysis of epoxy-fatty acids produces dihydroxy-fatty acids which are typically less biologically active than their parent epoxide. Efforts to develop sEH inhibitors have made available numerous compounds that show therapeutic efficacy and a wide margin of safety in a variety of different diseases, including non-alcoholic fatty liver disease, liver fibrosis, portal hypertension, and others. This review summarizes research efforts which characterize the applications, underlying effects, and molecular mechanisms of sEH inhibitors in these liver diseases and identifies gaps in knowledge for future research. Full article
(This article belongs to the Special Issue Non-Alcoholic Liver Injury)
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Open AccessArticle
Molecular Aggregation in Immune System Activation Studied by Dynamic Light Scattering
Biology 2020, 9(6), 123; https://doi.org/10.3390/biology9060123 - 12 Jun 2020
Viewed by 313
Abstract
Determination of the concentration and size of the circulating immune complexes in the blood is an essential part of diagnostics of immune diseases. In this work, we suggest using the dynamic light scattering method to determine the sizes of circulating immune complexes in [...] Read more.
Determination of the concentration and size of the circulating immune complexes in the blood is an essential part of diagnostics of immune diseases. In this work, we suggest using the dynamic light scattering method to determine the sizes of circulating immune complexes in blood serum. By the dynamic light scattering spectrometer, we found that for healthy and sick donors, the size and concentration of circulating immune complexes differed significantly. The dynamics of formation of these complexes were also examined in this work. It was shown that the formation of immune complexes in the blood of healthy donors is faster than the same reactions in the blood serum of donors with diseases. The results can be used in the diagnostics of the immune status and detection of chronic inflammation. We can recommend the dynamic light scattering method for implementation in biomedical diagnostics. Full article
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Open AccessReview
Revisiting the Impact of Neurodegenerative Proteins in Epilepsy: Focus on Alpha-Synuclein, Beta-Amyloid, and Tau
Biology 2020, 9(6), 122; https://doi.org/10.3390/biology9060122 - 12 Jun 2020
Viewed by 450
Abstract
Lack of disease-modifying therapy against epileptogenesis reflects the complexity of the disease pathogenesis as well as the high demand to explore novel treatment strategies. In the pursuit of developing new therapeutic strategies against epileptogenesis, neurodegenerative proteins have recently gained increased attention. Owing to [...] Read more.
Lack of disease-modifying therapy against epileptogenesis reflects the complexity of the disease pathogenesis as well as the high demand to explore novel treatment strategies. In the pursuit of developing new therapeutic strategies against epileptogenesis, neurodegenerative proteins have recently gained increased attention. Owing to the fact that neurodegenerative disease and epileptogenesis possibly share a common underlying mechanism, targeting neurodegenerative proteins against epileptogenesis might represent a promising therapeutic approach. Herein, we review the association of neurodegenerative proteins, such as α-synuclein, amyloid-beta (Aβ), and tau protein, with epilepsy. Providing insight into the α-synuclein, Aβ and tau protein-mediated neurodegeneration mechanisms, and their implication in epileptogenesis will pave the way towards the development of new agents and treatment strategies. Full article
Open AccessCommunication
Development of a Pulsatile Flow-Generating Circulatory Assist Device (K-Beat) for Use with Veno-Arterial Extracorporeal Membrane Oxygenation in a Pig Model Study
Biology 2020, 9(6), 121; https://doi.org/10.3390/biology9060121 - 12 Jun 2020
Viewed by 244
Abstract
Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) preserves the life of heart failure patients by providing an adequate oxygen supply and blood flow to vital organs. For patients with severe cardiogenic shock secondary to acute myocardial infarction or acute myocarditis, V-A ECMO is commonly [...] Read more.
Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) preserves the life of heart failure patients by providing an adequate oxygen supply and blood flow to vital organs. For patients with severe cardiogenic shock secondary to acute myocardial infarction or acute myocarditis, V-A ECMO is commonly used as the first choice among cardiac circulatory support devices. While V-A ECMO generates circulatory flow using a centrifugal pump, the provision of pulsatile flow is difficult. We previously reported our development of a new circulatory flow assist device (K-beat) for cardiac management with pulsatile flow. To obtain more efficient pulsatile assist flow (diastolic augmentation), an electrocardiogram (ECG)-analyzing device that can detect R waves and T waves increases the assist flow selectively in the diastole phase by controlling (opening and closing) the magnetic valve of the tamper. Here, we describe the first use of the K-beat on a large animal in combination with a clinical device. In addition, the diastolic augmentation effect of the K-beat as a circulatory flow assist device was examined in a pig V-A ECMO model. The K-beat was stopped every 60 min for a period of a few minutes, and blood pressure waveforms in the pulsatile and non-pulsatile phases were checked. This experiment showed that stable V-A ECMO could be achieved and that hemodynamics were managed in all animals. The pulsatile flow was provided in synchrony with the ECG in all cases. A diastolic augmentation waveform of femoral arterial pressure was confirmed in the pulsatile phase. K-beat could be useful in patients with severe heart failure. Full article
(This article belongs to the Section Medical Biology)
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Open AccessArticle
An Acromegaly Disease Zebrafish Model Reveals Decline in Body Stem Cell Number along with Signs of Premature Aging
Biology 2020, 9(6), 120; https://doi.org/10.3390/biology9060120 - 07 Jun 2020
Viewed by 703
Abstract
In our previous publication, it was shown that growth hormone (GH) excess in acromegaly affects the cell integrity of somatic cells through increased DNA damage throughout the body and impaired DNA repair pathways. Acromegaly is a hormone disorder pathological condition that develops as [...] Read more.
In our previous publication, it was shown that growth hormone (GH) excess in acromegaly affects the cell integrity of somatic cells through increased DNA damage throughout the body and impaired DNA repair pathways. Acromegaly is a hormone disorder pathological condition that develops as a result of growth hormone over-secretion from the pituitary gland. We produced a zebrafish acromegaly model to gain a better understanding of the excess GH effects at the cellular level. Here we show that the acromegaly zebrafish model progressively reduced the number of stem cells in different organs and increased oxidative stress in stem cells. Importantly, the decline in the stem cells was even more apparent than in aged fish. The controversy and debate over the use of GH as an anti-aging therapy have been going on for several years. In this study, excess GH induced aging signs such as increased senescence-associated (SA)-β-galactosidase staining of abdominal skin and similarity of the pattern of gene expression between aged and acromegaly zebrafish. Thus, this study highlights the role of excess GH in acromegaly stem cells. Full article
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Open AccessArticle
Dietary Supplementation with Omega-6 LC-PUFA-Rich Microalgae Regulates Mucosal Immune Response and Promotes Microbial Diversity in the Zebrafish Gut
Biology 2020, 9(6), 119; https://doi.org/10.3390/biology9060119 - 05 Jun 2020
Viewed by 427
Abstract
The effect of dietary omega-6 long-chain polyunsaturated fatty acid (LC-PUFA) on host microbiome and gut associated immune function in fish is unexplored. The effect of dietary supplementation with the omega-6 LC-PUFA-rich microalga Lobosphaera incisa wild type (WT) and its delta-5 desaturase mutant (MUT), [...] Read more.
The effect of dietary omega-6 long-chain polyunsaturated fatty acid (LC-PUFA) on host microbiome and gut associated immune function in fish is unexplored. The effect of dietary supplementation with the omega-6 LC-PUFA-rich microalga Lobosphaera incisa wild type (WT) and its delta-5 desaturase mutant (MUT), rich in arachidonic-acid and dihomo-gamma-linolenic acid (DGLA), respectively, on intestinal gene expression and microbial diversity was analyzed in zebrafish. For 1 month, fish were fed diets supplemented with broken biomass at 7.5% and 15% (w/w) of the two L. incisa strains and a control nonsupplemented commercial diet. Dietary supplementation resulted in elevated expression of genes related to arachidonic acid metabolism-cyclooxygenase 2 (cox-2), lipoxygenase 1(lox-1), anti-inflammatory cytokine-interleukin 10 (il-10), immune defense-lysozyme (lys), intestinal alkaline phosphatase (iap), complement (c3b), and antioxidants-catalase (cat), glutathione peroxidase (gpx). Microbiome analysis of the gut showed higher diversity indices for microbial communities in fish that were fed the supplemented diets compared to controls. Different treatment groups shared 237 operational taxonomic units (OTUs) that corresponded to the core microbiome, and unique OTUs were evident in different dietary groups. Overall, the zebrafish gut microbiome was dominated by the phylum Fusobacteria and Proteobacteria (averaging 38.4% and 34.6%, respectively), followed by Bacteroidetes (12.9%), Tenericutes, Planctomycetes, and Actinobacteria (at 3.1–1.3%). Significant interaction between some of the immune-related genes and microbial community was demonstrated. Full article
(This article belongs to the Special Issue The Path to Sustainable Production and Application of Algae)
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Open AccessArticle
Regional Phenotypic Differences of the Opener Muscle in Procambarus clarkii: Sarcomere Length, Fiber Diameter, and Force Development
Biology 2020, 9(6), 118; https://doi.org/10.3390/biology9060118 - 05 Jun 2020
Viewed by 362
Abstract
The opener muscle in the walking legs of the crayfish (Procambarus clarkii) has three distinct phenotypic regions although innervated by only one excitatory motor neuron. These regions (distal, central, and proximal) have varied biochemistry and physiology, including synaptic structure, troponin-T levels, [...] Read more.
The opener muscle in the walking legs of the crayfish (Procambarus clarkii) has three distinct phenotypic regions although innervated by only one excitatory motor neuron. These regions (distal, central, and proximal) have varied biochemistry and physiology, including synaptic structure, troponin-T levels, fiber diameter, input resistance, sarcomere length, and force generation. The force generated by the central fibers when the excitatory neuron was stimulated at 40 Hz was more than the force generated by the other regions. This increase in force was correlated with the central fibers having longer sarcomeres when measured in a relaxed claw. These data support the idea that the central fibers are tonic-like and that the proximal fibers are phasic-like. The addition of serotonin directly on the fibers was hypothesized to increase the force generated by the central fibers more than in the other regions, but this did not occur at 40-Hz stimulation. We hypothesized that the central distal fibers would generate the most force due to the arrangement on the apodeme. This study demonstrates how malleable the motor unit is with modulation and frequency of stimulation. Full article
(This article belongs to the Section Physiology)
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Open AccessArticle
Hydralazine Sensitizes to the Antifibrotic Effect of 5-Aza-2′-deoxycytidine in Hepatic Stellate Cells
Biology 2020, 9(6), 117; https://doi.org/10.3390/biology9060117 - 03 Jun 2020
Viewed by 364
Abstract
Background: Hepatic stellate cell (HSC) activation is essential for the development of liver fibrosis. Epigenetic machinery, such as DNA methylation, is largely involved in the regulation of gene expression during HSC activation. Although the pharmacological DNA demethylation of HSC using 5-aza-2′-deoxycytidine (5-aza-dC) yielded [...] Read more.
Background: Hepatic stellate cell (HSC) activation is essential for the development of liver fibrosis. Epigenetic machinery, such as DNA methylation, is largely involved in the regulation of gene expression during HSC activation. Although the pharmacological DNA demethylation of HSC using 5-aza-2′-deoxycytidine (5-aza-dC) yielded an antifibrotic effect, this drug has been reported to induce excessive cytotoxicity at a high dose. Hydralazine (HDZ), an antihypertensive agent, also exhibits non-nucleoside demethylating activity. However, the effect of HDZ on HSC activation remains unclear. In this study, we performed a combined treatment with 5-aza-dC and HDZ to obtain an enhanced antifibrotic effect with lower cytotoxicity. Methods: HSC-T6 cells were used as a rat HSC cell line in this study. The cells were cultivated together with 1 µM 5-Aza-dC and/or 10 µg/mL of HDZ, which were refreshed every 24 h until the 96 h treatment ended. Cell proliferation was measured using the WST-1 assay. The mRNA expression levels of peptidylprolyl isomerase A (Ppia), an internal control gene, collagen type I alpha 1 (Cola1), RAS protein activator like 1 (Rasal1), and phosphatase and tensin homolog deleted from chromosome 10 (Pten) were analyzed using quantitative reverse transcription polymerase chain reaction. Results: The percentage cell viability with 5-aza-dC, HDZ, and combined treatment vs. the vehicle-only control was 101.4 ± 2.5, 95.2 ± 5.7, and 79.2 ± 0.7 (p < 0.01 for 5-aza-dC and p < 0.01 for HDZ), respectively, in the 48 h treatment, and 52.4 ± 5.6, 65.9 ± 3.4, and 29.9 ± 1.3 (p < 0.01 for 5-aza-dC and p < 0.01 for HDZ), respectively, in the 96 h treatment. 5-Aza-dC and the combined treatment markedly decreased Cola1 mRNA levels. Accordingly, the expression levels of Rasal1 and Pten, which are antifibrotic genes, were increased by treatment after the 5-aza-dC and combined treatments. Moreover, single treatment with HDZ did not affect the expression levels of Cola1, Rasal1, or Pten. These results suggest that HDZ sensitizes to the antifibrotic effect of 5-aza-dC in HSC-T6 cells. The molecular mechanism underlying the sensitization to the antifibrotic effect of 5-aza-dC by HDZ remains to be elucidated. The expression levels of rat equilibrative nucleoside transporter genes (rEnt1, rEnt2, and rEnt3) were not affected by HDZ in this study. Conclusions: Further confirmation using primary HSCs and in vivo animal models is desirable, but combined treatment with 5-aza-dC and HDZ may be an effective therapy for liver fibrosis without severe adverse effects. Full article
(This article belongs to the Special Issue Non-Alcoholic Liver Injury)
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Open AccessReview
Saline and Arid Soils: Impact on Bacteria, Plants, and Their Interaction
Biology 2020, 9(6), 116; https://doi.org/10.3390/biology9060116 - 02 Jun 2020
Viewed by 415
Abstract
Salinity and drought are the most important abiotic stresses hampering crop growth and yield. It has been estimated that arid areas cover between 41% and 45% of the total Earth area worldwide. At the same time, the world’s population is going to soon [...] Read more.
Salinity and drought are the most important abiotic stresses hampering crop growth and yield. It has been estimated that arid areas cover between 41% and 45% of the total Earth area worldwide. At the same time, the world’s population is going to soon reach 9 billion and the survival of this huge amount of people is dependent on agricultural products. Plants growing in saline/arid soil shows low germination rate, short roots, reduced shoot biomass, and serious impairment of photosynthetic efficiency, thus leading to a substantial loss of crop productivity, resulting in significant economic damage. However, plants should not be considered as single entities, but as a superorganism, or a holobiont, resulting from the intimate interactions occurring between the plant and the associated microbiota. Consequently, it is very complex to define how the plant responds to stress on the basis of the interaction with its associated plant growth-promoting bacteria (PGPB). This review provides an overview of the physiological mechanisms involved in plant survival in arid and saline soils and aims at describing the interactions occurring between plants and its bacteriome in such perturbed environments. The potential of PGPB in supporting plant survival and fitness in these environmental conditions has been discussed. Full article
(This article belongs to the Special Issue Plant–Bacterial Interaction: From Molecule to Ecosystem)
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Open AccessArticle
Notch Inhibition via GSI Treatment Elevates Protein Synthesis in C2C12 Myotubes
Biology 2020, 9(6), 115; https://doi.org/10.3390/biology9060115 - 02 Jun 2020
Viewed by 501
Abstract
The role of Notch signaling is widely studied in skeletal muscle regeneration but little is known about its influences on muscle protein synthesis (MPS). The purpose of this study was to investigate whether Notch signaling is involved in the regulation of MPS. C2C12 [...] Read more.
The role of Notch signaling is widely studied in skeletal muscle regeneration but little is known about its influences on muscle protein synthesis (MPS). The purpose of this study was to investigate whether Notch signaling is involved in the regulation of MPS. C2C12 cells were treated with a γ-secretase inhibitor (GSI), to determine the effect of reduced Notch signaling on MPS and anabolic signaling markers. GSI treatment increased myotube hypertrophy by increasing myonuclear accretion (nuclei/myotube: p = 0.01) and myonuclear domain (myotube area per fusing nuclei: p < 0.001) in differentiating C2C12 cells. GSI treatment also elevated myotube hypertrophy in differentiated C2C12s (area/myotube; p = 0.01). In concert, GSI treatment augmented pmTOR Ser2448 (p = 0.01) and protein synthesis (using SUnSET method) in myotubes (p < 0.001). Examining protein expression upstream of mTOR revealed reductions in PTEN (p = 0.04), with subsequent elevations in pAKT Thr308 (p < 0.001) and pAKT Ser473 (p = 0.05). These findings reveal that GSI treatment elevates myotube hypertrophy through both augmentation of fusion and MPS. This study sheds light on the potential multifaceted roles of Notch within skeletal muscle. Furthermore, we have demonstrated that Notch may modulate the PTEN/AKT/mTOR pathway. Full article
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Open AccessArticle
Anti-Inflammatory and Physicochemical Characterization of the Croton rhamnifolioides Essential Oil Inclusion Complex in β-Cyclodextrin
Biology 2020, 9(6), 114; https://doi.org/10.3390/biology9060114 - 30 May 2020
Viewed by 522
Abstract
Croton rhamnifolioides is used in popular medicine for the treatment of inflammatory diseases. The objective of this study was to characterize and evaluate the anti-inflammatory effect of C. rhamnifolioides essential oil complexed in β-cyclodextrin (COEFC). The physicochemical characterization of the complexes was performed [...] Read more.
Croton rhamnifolioides is used in popular medicine for the treatment of inflammatory diseases. The objective of this study was to characterize and evaluate the anti-inflammatory effect of C. rhamnifolioides essential oil complexed in β-cyclodextrin (COEFC). The physicochemical characterization of the complexes was performed using different physical methods. The anti-inflammatory activity was evaluated in vivo by ear edema, paw edema, cotton pellet-induced granuloma, and vascular permeability by Evans blue extravasation. The mechanism of action was validated by molecular docking of the major constituent into the cyclooxygenase-2 (COX-2 enzyme). All doses of the COEFC reduced acute paw edema induced by carrageenan and dextran, as well as vascular permeability. Our results suggest the lowest effective dose of all samples inhibited the response induced by histamine or arachidonic acid as well as the granuloma formation. The complexation process showed that the pharmacological effects were maintained, however, showing similar results using much lower doses. The results demonstrated an involvement of the inhibition of pathways dependent on eicosanoids and histamine. Complexation of β-cyclodextrin/Essential oil (β-CD/EO) may present an important tool in the study of new compounds for the development of anti-inflammatory drugs. Full article
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Open AccessCorrection
Correction: Stalder, et al.; Value of SUVmax for the Prediction of Bone Invasion in Oral Squamous Cell Carcinoma. Biology 2020, 9, 23
Biology 2020, 9(6), 113; https://doi.org/10.3390/biology9060113 - 29 May 2020
Viewed by 370
Abstract
The authors would like to make a correction to their published paper [...] Full article
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Open AccessArticle
Metabolomic Reprogramming Detected by 1H-NMR Spectroscopy in Human Thyroid Cancer Tissues
Biology 2020, 9(6), 112; https://doi.org/10.3390/biology9060112 - 27 May 2020
Viewed by 441
Abstract
Thyroid cancer cells demonstrate an increase in oxidative stress and decreased antioxidant action, but the effects of this increased oxidative stress on cell function remain unknown. We aimed to identify changes in the metabolism of thyroid cancer cells caused by oxidative stress, using [...] Read more.
Thyroid cancer cells demonstrate an increase in oxidative stress and decreased antioxidant action, but the effects of this increased oxidative stress on cell function remain unknown. We aimed to identify changes in the metabolism of thyroid cancer cells caused by oxidative stress, using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Samples of thyroid cancer and healthy thyroid tissue were collected from patients undergoing thyroidectomy and analyzed with 1H-NMR spectroscopy for a wide array of metabolites. We found a significant increase in lactate content in thyroid cancer tissue compared to healthy tissue. Metabolomic analysis demonstrated significant differences between cancer tissue and healthy tissue, including an increase in aromatic amino acids, and an average decrease in citrate in thyroid cancer tissue. We hypothesize that these changes in metabolism may be due to an oxidative stress-related decrease in activity of the Krebs cycle, and a shift towards glycolysis in cancer tissue. Thus, thyroid cancer cells are able to reprogram their metabolic activity to survive in conditions of high oxidative stress and with a compromised antioxidant system. Our findings, for the first time, suggested a connection between oxidative stress and the alteration of the metabolic profile in thyroid tumors. Full article
(This article belongs to the Section Medical Biology)
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