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Life
Volume 11
Issue 10
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Life, Volume 11, Issue 10 (October 2021) – 116 articles

Cover Story (view full-size image): The combined use of clinical veterinary examinations, such as radiographic techniques and serum chemistry analysis, can obtain information on the health of animals and environmental factors. These examinations provide insight into the spatial, stressful, metabolic, and nutritional conditions of captive animals by deriving morphological and physiological results. These can be especially important in the animals that are raised for ex situ conservation because of severe population decline, for example, amphibians. Subsequently, better breeding conditions will also have positive effects on animal conservation efforts.View this paper
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20 pages, 1689 KiB  
Article
Genetics and Cognitive Vulnerability to Sleep Deprivation in Healthy Subjects: Interaction of ADORA2A, TNF-α and COMT Polymorphisms
by Mégane Erblang, Catherine Drogou, Danielle Gomez-Merino, Arnaud Rabat, Mathias Guillard, Pascal Van Beers, Michael Quiquempoix, Anne Boland, Jean François Deleuze, Robert Olaso, Céline Derbois, Maxime Prost, Rodolphe Dorey, Damien Léger, Claire Thomas, Mounir Chennaoui and Fabien Sauvet
Life 2021, 11(10), 1110; https://doi.org/10.3390/life11101110 - 19 Oct 2021
Cited by 2 | Viewed by 3383
Abstract
Several genetic polymorphisms differentiate between healthy individuals who are more cognitively vulnerable or resistant during total sleep deprivation (TSD). Common metrics of cognitive functioning for classifying vulnerable and resilient individuals include the Psychomotor Vigilance Test (PVT), Go/noGo executive inhibition task, and subjective daytime [...] Read more.
Several genetic polymorphisms differentiate between healthy individuals who are more cognitively vulnerable or resistant during total sleep deprivation (TSD). Common metrics of cognitive functioning for classifying vulnerable and resilient individuals include the Psychomotor Vigilance Test (PVT), Go/noGo executive inhibition task, and subjective daytime sleepiness. We evaluated the influence of 14 single-nucleotide polymorphisms (SNPs) on cognitive responses during total sleep deprivation (continuous wakefulness for 38 h) in 47 healthy subjects (age 37.0 ± 1.1 years). SNPs selected after a literature review included SNPs of the adenosine-A2A receptor gene (including the most studied rs5751876), pro-inflammatory cytokines (TNF-α, IL1-β, IL-6), catechol-O-methyl-transferase (COMT), and PER3. Subjects performed a psychomotor vigilance test (PVT) and a Go/noGo-inhibition task, and completed the Karolinska Sleepiness Scale (KSS) every 6 h during TSD. For PVT lapses (reaction time >500 ms), an interaction between SNP and SDT (p < 0.05) was observed for ADORA2A (rs5751862 and rs2236624) and TNF-α (rs1800629). During TSD, carriers of the A allele for ADORA2A (rs5751862) and TNF-α were significantly more impaired for cognitive responses than their respective ancestral G/G genotypes. Carriers of the ancestral G/G genotype of ADORA2A rs5751862 were found to be very similar to the most resilient subjects for PVT lapses and Go/noGo commission errors. Carriers of the ancestral G/G genotype of COMT were close to the most vulnerable subjects. ADORA2A (rs5751862) was significantly associated with COMT (rs4680) (p = 0.001). In conclusion, we show that genetic polymorphisms in ADORA2A (rs5751862), TNF-α (rs1800629), and COMT (rs4680) are involved in creating profiles of high vulnerability or high resilience to sleep deprivation. (NCT03859882). Full article
(This article belongs to the Section Genetics and Genomics)
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11 pages, 265 KiB  
Review
Psoriasis Therapy and Skin Cancer: A Review
by Beatriz Butrón-Bris, Esteban Daudén and Pedro Rodríguez-Jiménez
Life 2021, 11(10), 1109; https://doi.org/10.3390/life11101109 - 19 Oct 2021
Cited by 24 | Viewed by 3217
Abstract
Introduction: psoriasis is a chronic immune-mediated disease that is associated with several comorbidities, including an increased risk of malignancies, particularly skin cancer. A large number of studies have investigated whether psoriasis itself, psoriasis-associated comorbidities, or psoriasis treatment could lead to an increased risk [...] Read more.
Introduction: psoriasis is a chronic immune-mediated disease that is associated with several comorbidities, including an increased risk of malignancies, particularly skin cancer. A large number of studies have investigated whether psoriasis itself, psoriasis-associated comorbidities, or psoriasis treatment could lead to an increased risk of neoplasms. Methods: we reviewed the literature using the most important databases (PubMed, MEDLINE, ETHERIA). All articles pertaining to skin cancer associated with psoriasis disease and psoriasis therapy were included. In this review, we also discuss some of the potential underlying mechanisms for these associations, particularly regarding the multiple psoriasis therapies currently available, and their possible implications in higher incidences of skin cancer in these patients. Conclusion: evidence suggests that these patients might have a higher risk of cutaneous malignancies, especially for NMSC, compared with psoriasis-free patients. The reasons for this increased risk remain to be determined. However, high dose PUVA therapy, the immunosuppressive treatments used, and the comorbidities and habits frequently described in these patients seem to play a role in the pathogenesis of these tumors. Because of these facts, periodic screening for skin cancer is recommended in this population. Full article
(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)
18 pages, 1599 KiB  
Article
Diagnostic Efficacy of Voxel-Mirrored Homotopic Connectivity in Vascular Dementia as Compared to Alzheimer’s Related Neurodegenerative Diseases—A Resting State fMRI Study
by Eva Y. W. Cheung, Y. F. Shea, Patrick K. C. Chiu, Joseph S. K. Kwan and Henry K. F. Mak
Life 2021, 11(10), 1108; https://doi.org/10.3390/life11101108 - 19 Oct 2021
Cited by 14 | Viewed by 3008
Abstract
Previous studies have demonstrated that functional connectivity (FC) of different brain regions in resting state function MRI were abnormal in patients suffering from mild cognitive impairment (MCI) and Alzheimer’s disease (AD) when comparing to healthy controls (HC) using seed based, independent component analysis [...] Read more.
Previous studies have demonstrated that functional connectivity (FC) of different brain regions in resting state function MRI were abnormal in patients suffering from mild cognitive impairment (MCI) and Alzheimer’s disease (AD) when comparing to healthy controls (HC) using seed based, independent component analysis (ICA) or small world network techniques. A new technique called voxel-mirrored homotopic connectivity (VMHC) was used in the current study to evaluate the value of interhemispheric functional connectivity (IFC) as a diagnostic tool to differentiate vascular dementia (VD) from other Alzheimer’s related neurodegenerative diseases. Eighty-three participants were recruited from the university hospital memory clinic. A multidisciplinary panel formed by a neuroradiologist and two geriatricians classified the participants into VD (13), AD (16), MCI (29), and HC (25) based on clinical history, Montreal Cognitive Assessment Hong Kong version (HK‑MoCA) neuropsychological score, structural MRI, MR perfusion, and 18-F Flutametamol (amyloid) PET-CT findings of individual subjects. We adopted the calculation method used by Kelly et al. (2011) and Zuo et al. (2010) in obtaining VMHC maps. Specific patterns of VMHC maps were obtained for VD, AD, and MCI to HC comparison. VD showed significant reduction in VMHC in frontal orbital gyrus and gyrus rectus. Increased VMHC was observed in default mode network (DMN), executive control network (ECN), and the remaining salient network (SN) regions. AD showed a reduction of IFC in all DMN, ECN, and SN regions; whereas MCI showed VMHC reduction in vSN, and increased VMHC in DMN and ECN. When combining VMHC values of relevant brain regions, the accuracy was improved to 87%, 92%, and 83% for VD, AD, and MCI from HC, respectively, in receiver operating characteristic (ROC) analysis. Through studying the VMHC maps and using VMHC values in relevant brain regions, VMHC can be considered as a reliable diagnostic tool for VD, AD, and MCI from HC. Full article
(This article belongs to the Special Issue A New Era of Multidisciplinary Radiology: Fast Growing of Medical Radiation/Imaging/Artificial Intelligence Research)
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16 pages, 2267 KiB  
Article
The Inhibitory Effect of Noscapine on the In Vitro Cathepsin G-Induced Collagen Expression in Equine Endometrium
by Ana Amaral, Carina Fernandes, Anna Szóstek-Mioduchowska, Karolina Lukasik, Maria Rosa Rebordão, Pedro Pinto-Bravo, Dariusz Jan Skarzynski and Graça Ferreira-Dias
Life 2021, 11(10), 1107; https://doi.org/10.3390/life11101107 - 19 Oct 2021
Cited by 6 | Viewed by 2164
Abstract
Cathepsin G (CAT) is a protease released by neutrophils when forming neutrophil extracellular traps that was already associated with inducing type I collagen (COL1) in equine endometrium in vitro. Endometrosis is a fibrotic condition mainly characterized by COL1 deposition in the equine endometrium. [...] Read more.
Cathepsin G (CAT) is a protease released by neutrophils when forming neutrophil extracellular traps that was already associated with inducing type I collagen (COL1) in equine endometrium in vitro. Endometrosis is a fibrotic condition mainly characterized by COL1 deposition in the equine endometrium. The objective was to evaluate if noscapine (an alkaloid for cough treatment with anti-neoplastic and anti-fibrotic properties) would reduce COL1A2 transcription (evaluated by qPCR) and COL1 protein relative abundance (evaluated by western blot) induced by CAT in equine endometrial explants from follicular and mid-luteal phases treated for 24 or 48 h. The explants treated with CAT increased COL1 expression. Noscapine decreased COL1A2 transcription at both estrous cycle phases, but COL1 relative protein only at the follicular phase, both induced by CAT. Additionally, the noscapine anti-fibrotic action was found to be more effective in the follicular phase. The CAT treatment caused more fibrosis at the longest period of treatment, while noscapine acted better at the shortest time of treatment. Our results showed that noscapine could act as an anti-fibrotic drug in equine endometrosis by inhibiting CAT in vitro. Noscapine offers a new promising therapeutic tool for treating fibrosis as a single non-selective agent to be considered in the future. Full article
(This article belongs to the Section Physiology and Pathology)
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19 pages, 4426 KiB  
Article
Cell Populations Expressing Stemness-Associated Markers in Lung Adenocarcinoma
by Claudia Paterson, Ethan J. Kilmister, Helen D. Brasch, Nicholas Bockett, Josie Patel, Erin Paterson, Gordon Purdie, Sean Galvin, Paul F. Davis, Tinte Itinteang and Swee T. Tan
Life 2021, 11(10), 1106; https://doi.org/10.3390/life11101106 - 18 Oct 2021
Cited by 7 | Viewed by 3463
Abstract
The stemness-associated markers OCT4, NANOG, SOX2, KLF4 and c-MYC are expressed in numerous cancer types suggesting the presence of cancer stem cells (CSCs). Immunohistochemical (IHC) staining performed on 12 lung adenocarcinoma (LA) tissue samples showed protein expression of OCT4, NANOG, SOX2, KLF4 and [...] Read more.
The stemness-associated markers OCT4, NANOG, SOX2, KLF4 and c-MYC are expressed in numerous cancer types suggesting the presence of cancer stem cells (CSCs). Immunohistochemical (IHC) staining performed on 12 lung adenocarcinoma (LA) tissue samples showed protein expression of OCT4, NANOG, SOX2, KLF4 and c-MYC, and the CSC marker CD44. In situ hybridization (ISH) performed on six of the LA tissue samples showed mRNA expression of OCT4, NANOG, SOX2, KLF4 and c-MYC. Immunofluorescence staining performed on three of the tissue samples showed co-expression of OCT4 and c-MYC with NANOG, SOX2 and KLF4 by tumor gland cells, and expression of OCT4 and c-MYC exclusively by cells within the stroma. RT-qPCR performed on five LA-derived primary cell lines showed mRNA expression of all the markers except SOX2. Western blotting performed on four LA-derived primary cell lines demonstrated protein expression of all the markers except SOX2 and NANOG. Initial tumorsphere assays performed on four LA-derived primary cell lines demonstrated 0–80% of tumorspheres surpassing the 50 µm threshold. The expression of the stemness-associated markers OCT4, SOX2, NANOG, KFL4 and c-MYC by LA at the mRNA and protein level, and the unique expression patterns suggest a putative presence of CSC subpopulations within LA, which may be a novel therapeutic target for this cancer. Further functional studies are required to investigate the possession of stemness traits. Full article
(This article belongs to the Special Issue Origins, Properties, and Therapeutic Perspectives of Cancer Stem Cells)
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17 pages, 2495 KiB  
Article
The Circadian Rhythms of STAT3 in the Rat Pineal Gland and Its Involvement in Arylalkylamine-N-Acetyltransferase Regulation
by Simona Moravcová, Eva Filipovská, Veronika Spišská, Irena Svobodová, Jiří Novotný and Zdeňka Bendová
Life 2021, 11(10), 1105; https://doi.org/10.3390/life11101105 - 18 Oct 2021
Cited by 5 | Viewed by 2193
Abstract
In rodents, the melatonin production by the pineal gland is controlled through adrenergic signaling from the suprachiasmatic nuclei and regulation of the principal enzyme in its synthesis, arylalkylamine-N-acetyltransferase (AANAT). In the present study, we identified increased isoprenaline-induced aa-nat expression and nocturnal AANAT activity [...] Read more.
In rodents, the melatonin production by the pineal gland is controlled through adrenergic signaling from the suprachiasmatic nuclei and regulation of the principal enzyme in its synthesis, arylalkylamine-N-acetyltransferase (AANAT). In the present study, we identified increased isoprenaline-induced aa-nat expression and nocturnal AANAT activity in the pineal glands in response to the silencing of the signal transducer and activator of transcription 3 (STAT3) with siRNA or STAT3 inhibitors WP1066 and AZD1480. This AANAT activity enhancement in vivo did not interfere with light-induced AANAT suppression. Systemic or in vitro lipopolysaccharide (LPS) administration markedly increased Stat3 expression and STAT3 phosphorylation, but it did not significantly affect AANAT expression or activity. Simultaneous LPS administration and Stat3 silencing enhanced the aa-nat transcription and AANAT activity to a similar extent as Stat3 inhibition without LPS co-administration. Furthermore, we describe the circadian rhythmicity in Stat3 expression and the phosphorylated form of STAT3 protein in the rat pineal gland. Our data suggest that the higher nocturnal endogenous level of STAT3 in the pineal gland decelerates or hampers the process of NA-induced AANAT activation or affects the AANAT enzyme stability. Full article
(This article belongs to the Section Physiology and Pathology)
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24 pages, 8536 KiB  
Article
The Pupillary Light Reflex as a Biomarker of Concussion
by Frederick Robert Carrick, Sergio F. Azzolino, Melissa Hunfalvay, Guido Pagnacco, Elena Oggero, Ryan C. N. D’Arcy, Mahera Abdulrahman and Kiminobu Sugaya
Life 2021, 11(10), 1104; https://doi.org/10.3390/life11101104 - 18 Oct 2021
Cited by 14 | Viewed by 6741
Abstract
The size of our pupils changes continuously in response to variations in ambient light levels, a process known as the pupillary light reflex (PLR). The PLR is not a simple reflex as its function is modulated by cognitive brain function and any long-term [...] Read more.
The size of our pupils changes continuously in response to variations in ambient light levels, a process known as the pupillary light reflex (PLR). The PLR is not a simple reflex as its function is modulated by cognitive brain function and any long-term changes in brain function secondary to injury should cause a change in the parameters of the PLR. We performed a retrospective clinical review of the PLR of our patients using the BrightLamp Reflex iPhone app. The PLR variables of latency, maximum pupil diameter (MaxPD), minimum pupil diameter (MinPD), maximum constriction velocity (MCV), and the 75% recovery time (75% PRT) were associated with significant differences between subjects who had suffered a concussion and those that had not. There were also significant differences in PLR metrics over the life span and between genders and those subjects with and without symptoms. The differences in PLR metrics are modulated not only by concussion history but also by gender and whether or not the person has symptoms associated with a head injury. A concussive injury to the brain is associated with changes in the PLR that persist over the life span, representing biomarkers that might be used in clinical diagnosis, treatment, and decision making. Full article
(This article belongs to the Special Issue Frontiers in Neuroregeneration)
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20 pages, 561 KiB  
Review
Acute Inflammation in Cerebrovascular Disease: A Critical Reappraisal with Focus on Human Studies
by Rafael Azevedo Dias, Leonor Dias, Elsa Azevedo and Pedro Castro
Life 2021, 11(10), 1103; https://doi.org/10.3390/life11101103 - 17 Oct 2021
Cited by 7 | Viewed by 2863
Abstract
Recent attention has been focused on the field of inflammatory biomarkers associated with vascular disorders, regarding diagnosis, prognosis, and possible therapeutical targets. In this study, we aimed to perform a comprehensive review of the literature regarding the use of inflammatory biomarkers in stroke [...] Read more.
Recent attention has been focused on the field of inflammatory biomarkers associated with vascular disorders, regarding diagnosis, prognosis, and possible therapeutical targets. In this study, we aimed to perform a comprehensive review of the literature regarding the use of inflammatory biomarkers in stroke patients. We searched studies that evaluated inflammation biomarkers associated with Cerebrovascular Disease (CVD), namely, ischemic Stroke (IS), Intracerebral Hemorrhage (ICH) and Cerebral Venous Thrombosis (CVT). As of today, neutrophil–lymphocyte ratio (NLR) seems the be the most widely studied and accepted biomarker for cerebrovascular disease due to its easy access and availability. Although demonstrated as a prognostic risk factor, in IS, ICH and CVT, its diagnostic role is still under investigation. Several other prognostic factors could be used or even combined together into a diagnostic or prognostic index. Multiple inflammatory biomarkers appear to be involved in IS, ICH, and CVT. Blood inflammatory cells, easily measured and accessible at admission may provide information regarding accurate diagnosis and prognosis. Although not yet a reality, increasing evidence exists to suggest that these may become potential therapeutic targets, likely influencing or mitigating complications of CVD and improving prognosis. Nevertheless, further larger, well-designed randomized clinical trials are still needed to follow up this hypothesis. Full article
(This article belongs to the Special Issue Innovative Stroke Diagnostic and Treatment Strategies)
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14 pages, 1494 KiB  
Review
Hearing Loss and Cognitive Impairment: Epidemiology, Common Pathophysiological Findings, and Treatment Considerations
by Antonella Bisogno, Alfonso Scarpa, Stefano Di Girolamo, Pietro De Luca, Claudia Cassandro, Pasquale Viola, Filippo Ricciardiello, Antonio Greco, Marco De Vincentiis, Massimo Ralli and Arianna Di Stadio
Life 2021, 11(10), 1102; https://doi.org/10.3390/life11101102 - 17 Oct 2021
Cited by 19 | Viewed by 6665
Abstract
In recent years, there has been increasing research interest in the correlation between hearing impairment and cognitive decline, two conditions that have demonstrated a strong association. Hearing loss appears as a risk factor for cognitive impairment, especially among certain populations, notably nursing home [...] Read more.
In recent years, there has been increasing research interest in the correlation between hearing impairment and cognitive decline, two conditions that have demonstrated a strong association. Hearing loss appears as a risk factor for cognitive impairment, especially among certain populations, notably nursing home residents. Furthermore, hearing loss has been identified as a modifiable age-related condition linked to dementia, and it has been estimated that midlife hearing loss, if eliminated, might decrease the risk of dementia in the general population. Several mechanisms have been suggested to explain the pathologic connections between hearing loss and dementia; however, clear evidence is missing, and the common pathophysiological basis is still unclear. In this review, we discussed current knowledge about the relationship between hearing loss and dementia, and future perspectives in terms of the effects of hearing rehabilitation for early prevention of cognitive decline. Full article
(This article belongs to the Section Physiology and Pathology)
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26 pages, 4315 KiB  
Review
On Analyzing Capnogram as a Novel Method for Screening COVID-19: A Review on Assessment Methods for COVID-19
by M. B. Malarvili, Mushikiwabeza Alexie, Nadhira Dahari and Anhar Kamarudin
Life 2021, 11(10), 1101; https://doi.org/10.3390/life11101101 - 17 Oct 2021
Cited by 5 | Viewed by 4115
Abstract
In November 2019, the novel coronavirus disease COVID-19 was reported in Wuhan city, China, and was reported in other countries around the globe. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Strategies such as contact tracing and a vaccination [...] Read more.
In November 2019, the novel coronavirus disease COVID-19 was reported in Wuhan city, China, and was reported in other countries around the globe. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Strategies such as contact tracing and a vaccination program have been imposed to keep COVID-19 under control. Furthermore, a fast, noninvasive and reliable testing device is needed urgently to detect COVID-19, so that contact can be isolated and ringfenced before the virus spreads. Although the reverse transcription polymerase chain reaction (RT-PCR) test is considered the gold standard method for the diagnosis of SARS-CoV-2 infection, this test presents some limitations which cause delays in detecting the disease. The antigen rapid test (ART) test, on the other hand, is faster and cheaper than PCR, but is less sensitive, and may limit SARS-CoV-2 detection. While other tests are being developed, accurate, noninvasive and easy-to-use testing tools are in high demand for the rapid and extensive diagnosis of the disease. Therefore, this paper reviews current diagnostic methods for COVID-19. Following this, we propose the use of expired carbon dioxide (CO2) as an early screening tool for SARS-CoV-2 infection. This system has already been developed and has been tested on asthmatic patients. It has been proven that expired CO2, also known as capnogram, can help differentiate between respiratory conditions and, therefore, could be used to detect SARS-CoV-2 infection, as it causes respiratory tract-related diseases. Full article
(This article belongs to the Section Epidemiology)
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18 pages, 1387 KiB  
Article
Biological Invasion of Fish Parasite Neoergasilus japonicus (Harada, 1930) (Copepoda: Ergasilidae) in Lake Grand Laoucien, France: A Field Study on Life Cycle Parameters and Reasons for Unusual High Population Density
by Victor Alekseev, Corinne Cuoc, Dominique Jamet, Jean-Louis Jamet and Remi Chappaz
Life 2021, 11(10), 1100; https://doi.org/10.3390/life11101100 - 16 Oct 2021
Cited by 4 | Viewed by 2153
Abstract
The fish parasite, Neoergasilus japonicus (Harada, 1930), native to Eastern Siberia and the Amur River catchment area, invaded European water bodies in the middle of the last century, possibly due to the human-mediated distribution of fish in the Amur complex (i.e., the genera [...] Read more.
The fish parasite, Neoergasilus japonicus (Harada, 1930), native to Eastern Siberia and the Amur River catchment area, invaded European water bodies in the middle of the last century, possibly due to the human-mediated distribution of fish in the Amur complex (i.e., the genera Hypophthalmichthys and Ctenopharyngodon). In the deep karst lake, Grand Laoucien (Marseille area, France), this species had an unusually high population density (from 1000 ind./ m3 in zooplankton to 4000 ind./ m3 in the nearshore area) during the free-living period of its life cycle. The annual cycle of N. japonicus includes a 5-month overwintering of fertilized females attached to fish fins and, following this, a five- to six-generation chain from March to November, when the free-living stages in the population alternate with parasite females which attach to their hosts for breeding. The population density of the parasites in zooplankton increased exponentially from spring to autumn, which positively correlated with temperature. We found a strong correlation between N. japonicus density and the community development of microphytobenthos, but not between N. japonicus and phyto- or zooplankton dynamics. The local contributing factors included a seasonal three-fold decrease in water levels and the development of anoxia in profundal waters, which led to a high ambient fish density and thus susceptibility to the parasite. Although the free-living parasite represented only 1% of zooplankton production, it consumed up to 25% of small invertebrate productivity. The maximum intensity of infection reached 140 parasites per fish, or 4.14 per g of weight. The high infection of fish with this parasite, in our opinion, indicated the danger it poses to the local ichthyofauna, which first encountered this new parasite. Full article
(This article belongs to the Special Issue Biological Invasions and Biodiversity)
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10 pages, 1202 KiB  
Review
Wnt and β-Catenin Signaling in the Bone Metastasis of Prostate Cancer
by Zachary Kaplan, Steven P. Zielske, Kristina G. Ibrahim and Frank C. Cackowski
Life 2021, 11(10), 1099; https://doi.org/10.3390/life11101099 - 16 Oct 2021
Cited by 25 | Viewed by 3928
Abstract
Wnt family proteins and β-catenin are critical for the regulation of many developmental and oncogenic processes. Wnts are secreted protein ligands which signal using a canonical pathway, and involve the transcriptional co-activator β-catenin or non-canonical pathways that are independent of β-catenin. Bone metastasis [...] Read more.
Wnt family proteins and β-catenin are critical for the regulation of many developmental and oncogenic processes. Wnts are secreted protein ligands which signal using a canonical pathway, and involve the transcriptional co-activator β-catenin or non-canonical pathways that are independent of β-catenin. Bone metastasis is unfortunately a common occurrence in prostate cancer and can be conceptualized as a series of related steps or processes, most of which are regulated by Wnt ligands and/or β-catenin. At the primary tumor site, cancer cells often take on mesenchymal properties, termed epithelial mesenchymal transition (EMT), which are regulated in part by the Wnt receptor FZD4. Then, Wnt signaling, especially Wnt5A, is of importance as the cells circulate in the blood stream. Upon arriving in the bones, cancer cells migrate and take on stem-like or tumorigenic properties, as aided through Wnt or β-catenin signaling involving CHD11, CD24, and Wnt5A. Additionally, cancer cells can become dormant and evade therapy, in part due to regulation by Wnt5A. In the bones, E-selectin can aid in the reversal of EMT, a process termed mesenchymal epithelial transition (MET), as a part of metastatic tumorigenesis. Once bone tumors are established, Wnt/β-catenin signaling is involved in the suppression of osteoblast function largely through DKK1. Full article
(This article belongs to the Special Issue Prostate Cancer)
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15 pages, 1996 KiB  
Article
Short-Term Sleep Fragmentation Dysregulates Autophagy in a Brain Region-Specific Manner
by Yan Cheng, Woong-Ki Kim, Laurie L. Wellman, Larry D. Sanford and Ming-Lei Guo
Life 2021, 11(10), 1098; https://doi.org/10.3390/life11101098 - 16 Oct 2021
Cited by 11 | Viewed by 3182
Abstract
In this study, we investigated autophagy, glial activation status, and corticotropin releasing factor (CRF) signaling in the brains of mice after 5 days of sleep fragmentation (SF). Three different brain regions including the striatum, hippocampus, and frontal cortex were selected for examination based [...] Read more.
In this study, we investigated autophagy, glial activation status, and corticotropin releasing factor (CRF) signaling in the brains of mice after 5 days of sleep fragmentation (SF). Three different brain regions including the striatum, hippocampus, and frontal cortex were selected for examination based on roles in sleep regulation and sensitivity to sleep disruption. For autophagy, we monitored the levels of various autophagic induction markers including beclin1, LC3II, and p62 as well as the levels of lysosomal associated membrane protein 1 and 2 (LAMP1/2) and the transcription factor EB (TFEB) which are critical for lysosome function and autophagy maturation stage. For the status of microglia and astrocytes, we determined the levels of Iba1 and GFAP in these brain regions. We also measured the levels of CRF and its cognate receptors 1 and 2 (CRFR1/2). Our results showed that 5 days of SF dysregulated autophagy in the striatum and hippocampus but not in the frontal cortex. Additionally, 5 days of SF activated microglia in the striatum but not in the hippocampus or frontal cortex. In the striatum, CRFR2 but not CRFR1 was significantly increased in SF-experienced mice. CRF did not alter its mRNA levels in any of the three brain regions assessed. Our findings revealed that autophagy processes are sensitive to short-term SF in a region-specific manner and suggest that autophagy dysregulation may be a primary initiator for brain changes and functional impairments in the context of sleep disturbances and disorders. Full article
(This article belongs to the Section Physiology and Pathology)
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16 pages, 1246 KiB  
Review
CD8 T Cell Vaccines and a Cytomegalovirus-Based Vector Approach
by Marko Šustić, Maja Cokarić Brdovčak, Astrid Krmpotić and Stipan Jonjić
Life 2021, 11(10), 1097; https://doi.org/10.3390/life11101097 - 15 Oct 2021
Cited by 4 | Viewed by 3178
Abstract
The twentieth century witnessed a huge expansion in the number of vaccines used with great success in combating diseases, especially the ones caused by viral and bacterial pathogens. Despite this, several major public health threats, such as HIV, tuberculosis, malaria, and cancer, still [...] Read more.
The twentieth century witnessed a huge expansion in the number of vaccines used with great success in combating diseases, especially the ones caused by viral and bacterial pathogens. Despite this, several major public health threats, such as HIV, tuberculosis, malaria, and cancer, still pose an enormous humanitarian and economic burden. As vaccines based on the induction of protective, neutralizing antibodies have not managed to effectively combat these diseases, in recent decades, the focus has increasingly shifted towards the cellular immune response. There is substantial evidence demonstrating CD8 T cells as key players in the protection not only against many viral and bacterial pathogens, but also in the fight against neoplastic cells. Here, we present arguments for CD8 T cells to be considered as promising candidates for vaccine targeting. We discuss the heterogeneity of CD8 T cell populations and their contribution in the protection of the host. We also outline several strategies of using a common human pathogen, cytomegalovirus, as a vaccine vector since accumulated data strongly suggest it represents a promising approach to the development of novel vaccines against both pathogens and tumors. Full article
(This article belongs to the Special Issue Biology of Cytomegalovirus Infection)
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17 pages, 5384 KiB  
Article
Comprehensive Characterization of Androgen-Responsive circRNAs in Prostate Cancer
by Zhe Kong, Yali Lu, Xuechao Wan, Jun Luo, Dujian Li, Yan Huang, Chenji Wang, Yao Li and Yaoting Xu
Life 2021, 11(10), 1096; https://doi.org/10.3390/life11101096 - 15 Oct 2021
Cited by 5 | Viewed by 2407
Abstract
The androgen receptor (AR) signaling pathway plays an important role in the initiation and progression of prostate cancer. Circular RNAs (circRNAs), the novel noncoding RNAs without 5′ to 3′ polarity or 3′ poly (A), play an important role in multiple [...] Read more.
The androgen receptor (AR) signaling pathway plays an important role in the initiation and progression of prostate cancer. Circular RNAs (circRNAs), the novel noncoding RNAs without 5′ to 3′ polarity or 3′ poly (A), play an important role in multiple diseases. However, the potential roles of androgen-responsive circRNAs in prostate cancer remain unclear. In this study, we identified 3237 androgen-responsive circRNAs and 1954 androgen-responsive mRNAs after dihydrotestosterone (DHT) stimulation using microarray. Among them, the expression of 1296 androgen-responsive circRNAs was consistent with that of their parent genes, and we thought AR might regulate the expression of these circRNAs at the transcriptional level. In addition, 1941 circRNAs expression was not consistent with their parent genes, and we speculated that AR may regulate the expression of those circRNAs at the posttranscriptional level through affecting alternative splicing. Analyzing the androgen-responsive circRNAs regulated at the posttranscriptional level, we identified two key RNA binding proteins (RBPs), WTAP and TNRC6, using the circInteractome database, which may play important role in the biogenesis of androgen-responsive circRNAs. Furthermore, we explored the potential biological functions and predicted the molecular mechanisms of two dysregulated circRNAs (circNFIA and circZNF561) in prostate cancer. In this study, we revealed that circNFIA was upregulated in prostate cancer tissues and plasma samples from patients with prostate cancer; circNFIA may play an oncogenic role in prostate cancer. In contrast, circZNF561 was downregulated and may act as a tumor suppressor in prostate cancer. Our results suggest that androgen-responsive circRNAs might regulate the progression of prostate cancer and could be novel diagnostic biomarkers. Full article
(This article belongs to the Special Issue Androgen Receptor and AR-Related Signaling in Health and Disease)
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21 pages, 7336 KiB  
Review
Bioactive Natural Compounds with Antiplatelet and Anticoagulant Activity and Their Potential Role in the Treatment of Thrombotic Disorders
by Stefania Lamponi
Life 2021, 11(10), 1095; https://doi.org/10.3390/life11101095 - 15 Oct 2021
Cited by 18 | Viewed by 8535
Abstract
Natural anticoagulant drugs can be obtained from plants, rich in secondary bioactive metabolites which, in addition to being effective antioxidants, also possess anticoagulant and antiplatelet properties and, for this reason, can be excellent candidates for the treatment of thrombotic diseases. This review reports [...] Read more.
Natural anticoagulant drugs can be obtained from plants, rich in secondary bioactive metabolites which, in addition to being effective antioxidants, also possess anticoagulant and antiplatelet properties and, for this reason, can be excellent candidates for the treatment of thrombotic diseases. This review reports an overview of the hemostatic process and thrombotic disorders together with data on plants, more and less common from around the world, containing bioactive compounds characterized by antiplatelet and anticoagulant activity. The reported literature was obtained from Medline, PubMed, Elsevier, Web of Science, Google Scholar considering only articles in the English language, published in peer-reviewed journals. The number of citations of the articles and the impact factor of the journals were other parameters used to select the scientific papers to be included in the review. The analysis of the literature data selected demonstrates that many plants’ bioactive compounds show antiplatelet and anticoagulant activity that make them potential candidates to be used as new natural compounds able to interfere with both primary and secondary hemostasis. Moreover, they could be used together with anticoagulants currently administered in clinical practice to increase their efficacy and to reduce complications in the treatment of thrombotic disorders. Full article
(This article belongs to the Special Issue Bioactive Natural Compounds for Pharmaceutical and Nutraceutical Applications)
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16 pages, 7893 KiB  
Article
The Timing and Effects of Low-Dose Ethanol Treatment on Acetaminophen-Induced Liver Injury
by Fu-Chao Liu, Huang-Ping Yu, Chia-Chih Liao, An-Hsun Chou and Hung-Chen Lee
Life 2021, 11(10), 1094; https://doi.org/10.3390/life11101094 - 15 Oct 2021
Cited by 5 | Viewed by 2580
Abstract
Acetaminophen (APAP) overdose is the major cause of drug-induced liver injury and acute liver failure. Approximately 10% of APAP is metabolized by cytochrome P450 (CYP2E1) into toxic N-acetyl-p-benzoquinone imine (NAPQI). CYP2E1 also contributes to ethanol metabolism, especially during conditions of high blood [...] Read more.
Acetaminophen (APAP) overdose is the major cause of drug-induced liver injury and acute liver failure. Approximately 10% of APAP is metabolized by cytochrome P450 (CYP2E1) into toxic N-acetyl-p-benzoquinone imine (NAPQI). CYP2E1 also contributes to ethanol metabolism, especially during conditions of high blood ethanol concentration. Acute and chronic ethanol consumption appears to have opposite effects on APAP-induced liver injury. We determined the effects of different doses, pre- and post-treatment, and various schedules of ethanol exposure in APAP-induced liver injury. Treatment with ethanol (0.5 g/kg) after 1 h of APAP (300 mg/kg) administration decreased serum ALT levels, histopathological features, and inflammatory cell infiltration. Moreover, ethanol treatment 1 h after APAP treatment reduced APAP-induced liver injury compared with later administration. Interestingly, ethanol pretreatment did not provide any protective effect. Furthermore, ethanol treatment was associated with a significant decrease in ERK and AKT phosphorylation during the acute injury phase. Ethanol exposure also increased CYP2E1 expression and decreased PCNA expression during the liver regeneration phase. Full article
(This article belongs to the Special Issue Current Research in Inflammatory Response to Injury and Diseases)
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14 pages, 4316 KiB  
Article
Cryptic Diversity of Isaria-like Species in Guizhou, China
by Wanhao Chen, Jiandong Liang, Xiuxiu Ren, Jiehong Zhao, Yanfeng Han and Zongqi Liang
Life 2021, 11(10), 1093; https://doi.org/10.3390/life11101093 - 15 Oct 2021
Cited by 11 | Viewed by 2819
Abstract
Many Isaria-like species have recently been moved into more appropriate genera. However, more robust molecular phylogenetic analyses are still required for Isaria-like fungi to ensure accurate taxonomic identification. We analyzed these Isaria-like strains using multi-gene phylogenetics. Cryptic diversity was discovered [...] Read more.
Many Isaria-like species have recently been moved into more appropriate genera. However, more robust molecular phylogenetic analyses are still required for Isaria-like fungi to ensure accurate taxonomic identification. We analyzed these Isaria-like strains using multi-gene phylogenetics. Cryptic diversity was discovered in several Isaria farinosa strains, and two new species, Samsoniella pseudogunnii and S. pupicola, are proposed. Our results reveal that more attention needs to be paid to cryptic intraspecific diversity across different isolates and genotypes of the Isaria-like species, some of which will need to be transferred to Samsoniella. Interestingly, S. hepiali, with a very broad host distribution, has been widely used as a medicinal and edible cordycipitoid fungus. Full article
(This article belongs to the Special Issue Biodiversity and Ecology of Fungi in Terrestrial and Marine Ecosystems)
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12 pages, 2358 KiB  
Article
A Soft Voting Ensemble-Based Model for the Early Prediction of Idiopathic Pulmonary Fibrosis (IPF) Disease Severity in Lungs Disease Patients
by Sikandar Ali, Ali Hussain, Satyabrata Aich, Moo Suk Park, Man Pyo Chung, Sung Hwan Jeong, Jin Woo Song, Jae Ha Lee and Hee Cheol Kim
Life 2021, 11(10), 1092; https://doi.org/10.3390/life11101092 - 15 Oct 2021
Cited by 13 | Viewed by 2892
Abstract
Idiopathic pulmonary fibrosis, which is one of the lung diseases, is quite rare but fatal in nature. The disease is progressive, and detection of severity takes a long time as well as being quite tedious. With the advent of intelligent machine learning techniques, [...] Read more.
Idiopathic pulmonary fibrosis, which is one of the lung diseases, is quite rare but fatal in nature. The disease is progressive, and detection of severity takes a long time as well as being quite tedious. With the advent of intelligent machine learning techniques, and also the effectiveness of these techniques, it was possible to detect many lung diseases. So, in this paper, we have proposed a model that could be able to detect the severity of IPF at the early stage so that fatal situations can be controlled. For the development of this model, we used the IPF dataset of the Korean interstitial lung disease cohort data. First, we preprocessed the data while applying different preprocessing techniques and selected 26 highly relevant features from a total of 502 features for 2424 subjects. Second, we split the data into 80% training and 20% testing sets and applied oversampling on the training dataset. Third, we trained three state-of-the-art machine learning models and combined the results to develop a new soft voting ensemble-based model for the prediction of severity of IPF disease in patients with this chronic lung disease. Hyperparameter tuning was also performed to get the optimal performance of the model. Fourth, the performance of the proposed model was evaluated by calculating the accuracy, AUC, confusion matrix, precision, recall, and F1-score. Lastly, our proposed soft voting ensemble-based model achieved the accuracy of 0.7100, precision 0.6400, recall 0.7100, and F1-scores 0.6600. This proposed model will help the doctors, IPF patients, and physicians to diagnose the severity of the IPF disease in its early stages and assist them to take proactive measures to overcome this disease by enabling the doctors to take necessary decisions pertaining to the treatment of IPF disease. Full article
(This article belongs to the Special Issue Disease Prediction and Prevention: From Computational Biology and Artificial Intelligence to Epidemiology and Clinical Sciences)
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7 pages, 384 KiB  
Review
Cytoskeletal Tensegrity in Microgravity
by John Gardiner
Life 2021, 11(10), 1091; https://doi.org/10.3390/life11101091 - 15 Oct 2021
Cited by 3 | Viewed by 2620
Abstract
In order for Man to venture further into Space he will have to adapt to its conditions, including microgravity. Life as we know it has evolved on Earth with a substantial gravitational field. If they spend considerable time away from Earth, astronauts experience [...] Read more.
In order for Man to venture further into Space he will have to adapt to its conditions, including microgravity. Life as we know it has evolved on Earth with a substantial gravitational field. If they spend considerable time away from Earth, astronauts experience physiological, mental, and anatomical changes. It is not clear if these are pathological or adaptations. However, it is true that they experience difficulties on their return to stronger gravity. The cytoskeleton is a key site for the detection of gravitational force within the body, due to its tensegrity architecture. In order to understand what happens to living beings in space, we will need to unravel the role cytoskeletal tensegrity architecture plays in the building and function of cells, organs, the body, and mind. Full article
(This article belongs to the Special Issue Space Flight Factors and Cytoskeleton Organization)
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16 pages, 17579 KiB  
Article
Efficient Isolation of Bacterial RNAs Using Silica-Based Materials Modified with Ionic Liquids
by Patrícia Pereira, Augusto Q. Pedro, Márcia C. Neves, João C. Martins, Inês Rodrigues, Mara G. Freire and Fani Sousa
Life 2021, 11(10), 1090; https://doi.org/10.3390/life11101090 - 15 Oct 2021
Cited by 6 | Viewed by 2671
Abstract
High quality nucleic acids (with high integrity, purity, and biological activity) have become indispensable products of modern society, both in molecular diagnosis and to be used as biopharmaceuticals. As the current methods available for the extraction and purification of nucleic acids are laborious, [...] Read more.
High quality nucleic acids (with high integrity, purity, and biological activity) have become indispensable products of modern society, both in molecular diagnosis and to be used as biopharmaceuticals. As the current methods available for the extraction and purification of nucleic acids are laborious, time-consuming, and usually rely on the use of hazardous chemicals, there is an unmet need towards the development of more sustainable and cost-effective technologies for nucleic acids purification. Accordingly, this study addresses the preparation and evaluation of silica-based materials chemically modified with chloride-based ionic liquids (supported ionic liquids, SILs) as potential materials to effectively isolate RNAs. The investigated chloride-based SILs comprise the following cations: 1-methyl-3-propylimidazolium, triethylpropylammonium, dimethylbutylpropylammonium, and trioctylpropylammonium. All SILs were synthesized by us and characterized by solid-state 13C Nuclear Magnetic Resonance (NMR), Scanning Electron Microscopy (SEM), elemental analysis, and zeta potential measurements, confirming the successful covalent attachment of each IL cation with no relevant changes in the morphology of materials. Their innovative application as chromatographic supports for the isolation of recombinant RNA was then evaluated. Adsorption kinetics of transfer RNA (tRNA) on the modified silica-based materials were investigated at 25 °C. Irrespective to the immobilized IL, the adsorption experimental data are better described by a pseudo first-order model, and maximum tRNA binding capacities of circa 16 µmol of tRNA/g of material were achieved with silica modified with 1-methyl-3-propylimidazolium chloride and dimethylbutylpropylammonium chloride. Furthermore, the multimodal character displayed by SILs was explored towards the purification of tRNA from Escherichia coli lysates, which in addition to tRNA contain ribosomal RNA and genomic DNA. The best performance on the tRNA isolation was achieved with SILs comprising 1-methyl-3-propylimidazolium chloride and dimethylbutylpropylammonium chloride. Overall, the IL modified silica-based materials represent a more efficient, sustainable, and cost-effective technology for the purification of bacterial RNAs, paving the way for their use in the purification of distinct biomolecules or nucleic acids from other sources. Full article
(This article belongs to the Special Issue Recent Trends and Technological Developments in Biopharmaceuticals Manufacturing)
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14 pages, 2129 KiB  
Article
Examination of Physiological and Morphological Differences between Farm-Bred and Wild Black-Spotted Pond Frogs (Pelophylax nigromaculatus)
by Jun-Kyu Park, Jeong Bae Kim and Yuno Do
Life 2021, 11(10), 1089; https://doi.org/10.3390/life11101089 - 15 Oct 2021
Cited by 5 | Viewed by 2994
Abstract
Due to the decline in the population and the difficulty of in situ conservation, several anuran species are being reared in captivity. In this study, we identified physiological and morphological differences between farm-bred and wild frogs. Nine different serum components were used as [...] Read more.
Due to the decline in the population and the difficulty of in situ conservation, several anuran species are being reared in captivity. In this study, we identified physiological and morphological differences between farm-bred and wild frogs. Nine different serum components were used as indicators of osmotic pressure, homeostatic state, organ function, and nutritional status of farm-bred frogs and wild frogs, while radiographic techniques were used to visualize differences in bone mineral density and body composition ratio. Additionally, X-ray skeletal images were used for morphological analysis to estimate differences in locomotory performance between the two groups. Wild frogs harbor traits that aid in better locomotory performance than farm-bred frogs. They also have a relatively lower fat content ratio and higher calcium and phosphorus serum levels than farm-bred frogs, suggesting a difference in nutritional status. However, hepatic stress was higher in wild frogs than in farm-bred frogs. Veterinary clinical examinations allow for the identification of differences in nutritional and morphological conditions between farm-bred and wild frogs. Determining the health of animals can help improve their living conditions, eliminate conditions that can negatively affect them, and effectively manage them on farms, in zoos, and at ex situ conservation institutes. Full article
(This article belongs to the Special Issue Strategies and Approaches for Improvement of Aquaculture)
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17 pages, 2229 KiB  
Review
Molecular and Cellular Mechanisms of Vascular Development in Zebrafish
by Jean Eberlein, Lukas Herdt, Julian Malchow, Annegret Rittershaus, Stefan Baumeister and Christian SM Helker
Life 2021, 11(10), 1088; https://doi.org/10.3390/life11101088 - 15 Oct 2021
Cited by 7 | Viewed by 6145
Abstract
The establishment of a functional cardiovascular system is crucial for the development of all vertebrates. Defects in the development of the cardiovascular system lead to cardiovascular diseases, which are among the top 10 causes of death worldwide. However, we are just beginning to [...] Read more.
The establishment of a functional cardiovascular system is crucial for the development of all vertebrates. Defects in the development of the cardiovascular system lead to cardiovascular diseases, which are among the top 10 causes of death worldwide. However, we are just beginning to understand which signaling pathways guide blood vessel growth in different tissues and organs. The advantages of the model organism zebrafish (Danio rerio) helped to identify novel cellular and molecular mechanisms of vascular growth. In this review we will discuss the current knowledge of vasculogenesis and angiogenesis in the zebrafish embryo. In particular, we describe the molecular mechanisms that contribute to the formation of blood vessels in different vascular beds within the embryo. Full article
(This article belongs to the Special Issue Advances in Zebrafish Genetics and Applications to Study the Cardiovascular System)
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15 pages, 3796 KiB  
Article
A Novel RNA Synthesis Inhibitor, STK160830, Has Negligible DNA-Intercalating Activity for Triggering A p53 Response, and Can Inhibit p53-Dependent Apoptosis
by Akinori Morita, Shintaro Ochi, Hidetoshi Satoh, Shohei Ujita, Yosuke Matsushita, Kasumi Tada, Mihiro Toyoda, Yuichi Nishiyama, Kosuke Mizuno, Yuichi Deguchi, Keiji Suzuki, Yoshimasa Tanaka, Hiroshi Ueda, Toshiya Inaba, Yoshio Hosoi and Shin Aoki
Life 2021, 11(10), 1087; https://doi.org/10.3390/life11101087 - 15 Oct 2021
Cited by 3 | Viewed by 2489
Abstract
RNA synthesis inhibitors and protein synthesis inhibitors are useful for investigating whether biological events with unknown mechanisms require transcription or translation; however, the dependence of RNA synthesis has been difficult to verify because many RNA synthesis inhibitors cause adverse events that trigger a [...] Read more.
RNA synthesis inhibitors and protein synthesis inhibitors are useful for investigating whether biological events with unknown mechanisms require transcription or translation; however, the dependence of RNA synthesis has been difficult to verify because many RNA synthesis inhibitors cause adverse events that trigger a p53 response. In this study, we screened a library containing 9600 core compounds and obtained STK160830 that shows anti-apoptotic effects in irradiated wild-type-p53-bearing human T-cell leukemia MOLT-4 cells and murine thymocytes. In many of the p53-impaired cells and p53-knockdown cells tested, STK160830 did not show a remarkable anti-apoptotic effect, suggesting that the anti-apoptotic activity is p53-dependent. In the expression analysis of p53, p53-target gene products, and reference proteins by immunoblotting, STK160830 down-regulated the expression of many of the proteins examined, and the downregulation correlated strongly with its inhibitory effect on cell death. mRNA expression analyses by qPCR and nascent RNA capture kit revealed that STK160830 showed a decreased mRNA expression, which was similar to that induced by the RNA synthesis inhibitor actinomycin D but differed to some extent. Furthermore, unlike other RNA synthesis inhibitors such as actinomycin D, p53 accumulation by STK160830 alone was negligible, and a DNA melting-curve analysis showed very weak DNA-intercalating activity, indicating that STK160830 is a useful inhibitor for RNA synthesis without triggering p53-mediated damage responses. Full article
(This article belongs to the Section Radiobiology and Nuclear Medicine)
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14 pages, 760 KiB  
Article
Leptin Receptor (rs1137101) and Brain-Derived Neurotrophic Factor (rs925946) Gene Variants Are Associated with Obesity in the Early- but Not in the Late-Onset Population of Hungarian Psoriatic Patients
by Zita Szentkereszty-Kovács, Szilvia Fiatal, Eszter Anna Janka, Dóra Kovács, Andrea Szegedi, Éva Remenyik and Dániel Törőcsik
Life 2021, 11(10), 1086; https://doi.org/10.3390/life11101086 - 14 Oct 2021
Cited by 6 | Viewed by 2344
Abstract
Background: Psoriatic patients have considerably higher odds of being obese compared with the general population; however, the exact pathophysiological link between psoriasis and obesity needs to be elucidated. Methods: To investigate the association of psoriasis with established obesity-related gene variants, we conducted a [...] Read more.
Background: Psoriatic patients have considerably higher odds of being obese compared with the general population; however, the exact pathophysiological link between psoriasis and obesity needs to be elucidated. Methods: To investigate the association of psoriasis with established obesity-related gene variants, we conducted a population-based case-control study including 3541 subjects (574 psoriasis cases and 2967 controls from the general Hungarian population). Genotyping of 20 SNPs at ADIPOQ, BDNF, FTO, GNPDA2, LEPR, MC4R, NEGR1, NPY, PPARG, TMEM18, and UCP2 were determined, and differences in genotype and allele distributions were investigated. Multiple logistic regression analyses were implemented. Results: Analysis revealed an association between the G allele of the rs1137101 polymorphism (LEPR gene) and obesity risk (OR: 3.30 (1.45; 7.50), p = 0.004) in the early-onset group of psoriatic patients. Furthermore, the T allele of rs925946 polymorphism (BDNF gene) was also associated with increased risk of obesity in early-onset psoriasis (OR: 2.26 (1.24; 4.14), p = 0.008). Conclusions: Our results suggest that in psoriatic patients, there are prominent differences in the causes of obesity that should be accounted for, including not only environmental factors but also patient characteristics, such as the time of disease onset as well as genetic factors. Full article
(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)
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14 pages, 1552 KiB  
Article
Modified VMAT Plans for Locally Advanced Centrally Located Non-Small Cell Lung Cancer (NSCLC)
by Eva Y. W. Cheung, Virginia H. Y. Kwong, Fandy Y. C. Chan, Dominic Y. T. Cheng, Janice K. Y. Cheng, Sapphire H. Y. Yung, Kiris T. K. Chan, Kelly T. Y. Cheung, Tracy S. W. Cheung and Janna C. L. Yiu
Life 2021, 11(10), 1085; https://doi.org/10.3390/life11101085 - 14 Oct 2021
Cited by 2 | Viewed by 2733
Abstract
Objectives: This study aimed to find the optimal radiotherapy VMAT plans, that achieved high conformity and homogeneity to the planned target volume (PTV), and minimize the dose to nearby organs at risk including the non-PTV lung, heart and oesophagus for patients with centrally [...] Read more.
Objectives: This study aimed to find the optimal radiotherapy VMAT plans, that achieved high conformity and homogeneity to the planned target volume (PTV), and minimize the dose to nearby organs at risk including the non-PTV lung, heart and oesophagus for patients with centrally located non-small Cell Lung Cancer. Methods: A total of 18 patients who were treated for stage III centrally located non-small Cell Lung Cancer were selected retrospectively for this study. Identical CT datasets, 4D CT and structure dataset were used for radiotherapy planning based on single-planar VMAT (SP-VMAT), dual-planar VMAT (DP-VMAT) and Hybrid VMAT (H-VMAT). For SP-VMAT, one full arc and two half arcs were created on single-plane with couch at 0°. For DP-VMAT, one full arc was created with couch at 0°, and two half arcs with couch rotation of 330° or 30°. For H-VMAT, anterior-posterior opposing fixed beam and two half arcs were planned at couch at 0°. Dose constraints were adhered to the RTOG0617. Dose volumetric parameters were collected for statistical analysis. Results: There were no significant differences for the PTV, HI, CI between the SP-VMAT, DP-VMAT and H-VMAT. For the non-PTV lungs, Dmean, V20, V10, V5, D1500 and D1000 were significantly lower (2.05 Gy, 6.47%, 15.89%, 11.66% 4.17 Gy and 5.47 Gy respectively) in H-VMAT than that of SP-VMAT (all p < 0.001). For the oesophagus, Dmax, Dmean, V30 and V18.8 of H-VMAT were 0.08 Gy, 1.73 Gy, 5.54% and 7.17% lower than that of the SP-VMAT plan. For the heart, Dmean, V34, V28, V20 and V10 of DP-VMAT were lower than that of SP-VMAT by 1.45 Gy, 0.65%, 1.74%, 4.8% and 7.11% respectively. Conclusion: The proposed H-VMAT showed more favourable plan quality than the SP-VMAT for centrally located stage III NSCLC, in particular for non-PTV lungs and the oesophagus. It will benefit patients, especially those who planned for immunotherapy (Durvalumab) after standard chemo-irradiation. The proposed DP-VMAT plan showed significant dose reduction to the heart when compared to the H-VMAT plan. Full article
(This article belongs to the Special Issue Modern Radiotherapy Concepts for Hematological and Solid Malignancies)
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15 pages, 2045 KiB  
Article
Double Recombinant Vaccinia Virus: A Candidate Drug against Human Glioblastoma
by Natalia Vasileva, Alisa Ageenko, Maria Dmitrieva, Anna Nushtaeva, Sergey Mishinov, Galina Kochneva, Vladimir Richter and Elena Kuligina
Life 2021, 11(10), 1084; https://doi.org/10.3390/life11101084 - 14 Oct 2021
Cited by 17 | Viewed by 2708
Abstract
Glioblastoma is one of the most aggressive brain tumors. Given the poor prognosis of this disease, novel methods for glioblastoma treatment are needed. Virotherapy is one of the most actively developed approaches for cancer therapy today. VV-GMCSF-Lact is a recombinant vaccinia virus with [...] Read more.
Glioblastoma is one of the most aggressive brain tumors. Given the poor prognosis of this disease, novel methods for glioblastoma treatment are needed. Virotherapy is one of the most actively developed approaches for cancer therapy today. VV-GMCSF-Lact is a recombinant vaccinia virus with deletions of the viral thymidine kinase and growth factor genes and insertions of the granulocyte–macrophage colony-stimulating factor and oncotoxic protein lactaptin genes. The virus has high cytotoxic activity against human cancer cells of various histogenesis and antitumor efficacy against breast cancer. In this work, we show VV-GMCSF-Lact to be a promising therapeutic agent for glioblastoma treatment. VV-GMCSF-Lact effectively decreases the viability of glioblastoma cells of both immortalized and patient-derived cultures in vitro, crosses the blood–brain barrier, selectively replicates into orthotopically transplanted human glioblastoma when intravenously injected, and inhibits glioblastoma xenograft and metastasis growth when injected intratumorally. Full article
(This article belongs to the Collection Tumor Progression, Microenvironments, and Therapeutics)
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15 pages, 3064 KiB  
Article
Slosh Simulation in a Computer Model of Canine Syringomyelia
by Srdjan Cirovic and Clare Rusbridge
Life 2021, 11(10), 1083; https://doi.org/10.3390/life11101083 - 14 Oct 2021
Cited by 2 | Viewed by 3895
Abstract
The exact pathogenesis of syringomyelia is unknown. Epidural venous distention during raised intrathoracic pressure (Valsalva) may cause impulsive movement of fluid (“slosh”) within the syrinx. Such a slosh mechanism is a proposed cause of syrinx dissection into spinal cord parenchyma resulting in craniocaudal [...] Read more.
The exact pathogenesis of syringomyelia is unknown. Epidural venous distention during raised intrathoracic pressure (Valsalva) may cause impulsive movement of fluid (“slosh”) within the syrinx. Such a slosh mechanism is a proposed cause of syrinx dissection into spinal cord parenchyma resulting in craniocaudal propagation of the cavity. We sought to test the “slosh” hypothesis by epidural excitation of CSF pulse in a computer model of canine syringomyelia. Our previously developed canine syringomyelia computer model was modified to include an epidural pressure pulse. Simulations were run for: cord free of cavities; cord with small syringes at different locations; and cord with a syrinx that was progressively expanding caudally. If small syringes are present, there are peaks of stress at those locations. This effect is most pronounced at the locations at which syringes initially form. When a syrinx is expanding caudally, the peak stress is typically at the caudal end of the syrinx. However, when the syrinx reaches the lumbar region; the stress becomes moderate. The findings support the “slosh” hypothesis, suggesting that small cervical syringes may propagate caudally. However, when the syrinx is large, there is less focal stress, which may explain why a syrinx can rapidly expand but then remain unchanged in shape over years. Full article
(This article belongs to the Special Issue New Horizons in Veterinary Neurology)
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25 pages, 3749 KiB  
Review
Structure, Activity, and Function of the Protein Lysine Methyltransferase G9a
by Coralie Poulard, Lara M. Noureddine, Ludivine Pruvost and Muriel Le Romancer
Life 2021, 11(10), 1082; https://doi.org/10.3390/life11101082 - 14 Oct 2021
Cited by 27 | Viewed by 5660
Abstract
G9a is a lysine methyltransferase catalyzing the majority of histone H3 mono- and dimethylation at Lys-9 (H3K9), responsible for transcriptional repression events in euchromatin. G9a has been shown to methylate various lysine residues of non-histone proteins and acts as a coactivator for several [...] Read more.
G9a is a lysine methyltransferase catalyzing the majority of histone H3 mono- and dimethylation at Lys-9 (H3K9), responsible for transcriptional repression events in euchromatin. G9a has been shown to methylate various lysine residues of non-histone proteins and acts as a coactivator for several transcription factors. This review will provide an overview of the structural features of G9a and its paralog called G9a-like protein (GLP), explore the biochemical features of G9a, and describe its post-translational modifications and the specific inhibitors available to target its catalytic activity. Aside from its role on histone substrates, the review will highlight some non-histone targets of G9a, in order gain insight into their role in specific cellular mechanisms. Indeed, G9a was largely described to be involved in embryonic development, hypoxia, and DNA repair. Finally, the involvement of G9a in cancer biology will be presented. Full article
(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)
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11 pages, 2104 KiB  
Article
Foliar Fungal Endophytes in a Tree Diversity Experiment Are Driven by the Identity but Not the Diversity of Tree Species
by Stephan Kambach, Christopher Sadlowski, Derek Peršoh, Marco Alexandre Guerreiro, Harald Auge, Oliver Röhl and Helge Bruelheide
Life 2021, 11(10), 1081; https://doi.org/10.3390/life11101081 - 13 Oct 2021
Cited by 4 | Viewed by 2317
Abstract
Symbiotic foliar fungal endophytes can have beneficial effects on host trees and might alleviate climate-induced stressors. Whether and how the community of foliar endophytes is dependent on the tree neighborhood is still under debate with contradicting results from different tree diversity experiments. Here, [...] Read more.
Symbiotic foliar fungal endophytes can have beneficial effects on host trees and might alleviate climate-induced stressors. Whether and how the community of foliar endophytes is dependent on the tree neighborhood is still under debate with contradicting results from different tree diversity experiments. Here, we present our finding regarding the effect of the tree neighborhood from the temperate, densely planted and 12-years-old Kreinitz tree diversity experiment. We used linear models, redundancy analysis, Procrustes analysis and Holm-corrected multiple t-tests to quantify the effects of the plot-level tree neighborhood on the diversity and composition of foliar fungal endophytes in Fagus sylvatica, Quercus petraea and Picea abies. Against our expectations, we did not find an effect of tree diversity on endophyte diversity. Endophyte composition, however, was driven by the identity of the host species. Thirteen endophytes where overabundant in tree species mixtures, which might indicate frequent spillover or positive interactions between foliar endophytes. The independence of the diversity of endophytes from the diversity of tree species might be attributed to the small plot size and the high density of tree individuals. However, the mechanistic causes for these cryptic relationships still remain to be uncovered. Full article
(This article belongs to the Special Issue Biodiversity and Ecology of Fungi in Terrestrial and Marine Ecosystems)
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