Life | Editor’s choice Articles

7 pages, 594 KB

Open AccessEditor’s ChoicePerspective

Build-a-Cell: Engineering a Synthetic Cell Community

by Caroline Frischmon, Carlise Sorenson, Michael Winikoff and Katarzyna P. Adamala

Life 2021, 11(11), 1176; https://doi.org/10.3390/life11111176 - 3 Nov 2021

Cited by 19 | Viewed by 3624

Build-a-Cell is a global network of researchers that aims to develop synthetic living cells within the next decade. These cells will revolutionize the biotechnology industry by providing scientists and engineers with a more complete understanding of biology. Researchers can already replicate many cellular [...] Read more.

Build-a-Cell is a global network of researchers that aims to develop synthetic living cells within the next decade. These cells will revolutionize the biotechnology industry by providing scientists and engineers with a more complete understanding of biology. Researchers can already replicate many cellular functions individually, but combining them into a single cell remains a significant challenge. This integration step will require the type of large-scale collaboration made possible by Build-a-Cell’s open, collective structure. Beyond the lab, Build-a-Cell addresses policy issues and biosecurity concerns associated with synthetic cells. The following review discusses Build-a-Cell’s history, function, and goals. Full article

(This article belongs to the Special Issue Trends and Outlooks in Synthetic Biology: A Special Issue for Celebrating 10 Years of Life and Its Landmarks)

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12 pages, 278 KB

Open AccessEditor’s ChoiceReview

Vitamin C Intervention for Critical COVID-19: A Pragmatic Review of the Current Level of Evidence

by Patrick Holford, Anitra C. Carr, Masuma Zawari and Marcela P. Vizcaychipi

Life 2021, 11(11), 1166; https://doi.org/10.3390/life11111166 - 1 Nov 2021

Cited by 19 | Viewed by 12437

Abstract

Severe respiratory infections are characterized by elevated inflammation and generation of reactive oxygen species (ROS) which may lead to a decrease in antioxidants such as vitamin C and a higher requirement for the vitamin. Administration of intravenous vitamin C to patients with pneumonia [...] Read more.

Severe respiratory infections are characterized by elevated inflammation and generation of reactive oxygen species (ROS) which may lead to a decrease in antioxidants such as vitamin C and a higher requirement for the vitamin. Administration of intravenous vitamin C to patients with pneumonia and sepsis appears to decrease the severity of the disease and potentially improve survival rate. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes pneumonia, sepsis and acute respiratory distress syndrome (ARDS) in severe cases, and is referred to as coronavirus disease 2019 (COVID-19). Patients with COVID-19 infection also appear to have depleted vitamin C status and require additional supplementation of vitamin C during the acute phase of the disease. To date there have been 12 vitamin C and COVID-19 trials published, including five randomised controlled trials (RCTs) and seven retrospective cohort studies. The current level of evidence from the RCTs suggests that intravenous vitamin C intervention may improve oxygenation parameters, reduce inflammatory markers, decrease days in hospital and reduce mortality, particularly in the more severely ill patients. High doses of oral vitamin C supplementation may also improve the rate of recovery in less severe cases. No adverse events have been reported in published vitamin C clinical trials in COVID-19 patients. Upcoming findings from larger RCTs will provide additional evidence on vitamin supplementation in COVID-19 patients. Full article

(This article belongs to the Special Issue Antimicrobial Mechanisms of Vitamin C)

12 pages, 1739 KB

Open AccessEditor’s ChoiceArticle

Neuromuscular Activity during Cycling Performance in Hot/Dry and Hot/Humid Conditions

by Michelle Baillot, Olivier Hue, Trong Than Tran and Sophie Antoine-Jonville

Life 2021, 11(11), 1149; https://doi.org/10.3390/life11111149 - 28 Oct 2021

Cited by 5 | Viewed by 2568

Abstract

To determine the relationships between limiting factors and neuromuscular activity during a self-paced 20-km cycling time trial and evaluate the effect of environmental conditions on fatigue indices. Methods: Ten endurance-trained and heat-acclimated athletes performed in three conditions (ambient temperature, relative humidity): HUMID (30 [...] Read more.

To determine the relationships between limiting factors and neuromuscular activity during a self-paced 20-km cycling time trial and evaluate the effect of environmental conditions on fatigue indices. Methods: Ten endurance-trained and heat-acclimated athletes performed in three conditions (ambient temperature, relative humidity): HUMID (30 °C, 90%), DRY (35 °C, 46%) and NEUTRAL (22 °C, 55%). Voluntary muscular contractions and electromagnetic stimulations were recorded before and after the time trials to assess fatigue. The data on performance, temperature, heat storage, electromyogram, heart rate and rating of perceived exertion data were analyzed. Results: Performance was impaired in DRY and HUMID compared with NEUTRAL environment (p < 0.05). The force developed by the vastus lateral muscle during stimulation of the femoral nerve remained unchanged across conditions. The percentage of integrated electromyogram activity, normalized by the value attained during the pre-trial maximal voluntary contraction, decreased significantly throughout the trial only in HUMID condition (p < 0.01). Neuromuscular activity in peripheral skeletal muscle started to fall from the 11th km in HUMID and the 15th km in DRY condition, although core temperature did not reach critical values. Conclusions: These alterations suggest that afferences from core/skin temperature regulate the central neural motor drive, reducing the active muscle recruited during prolonged exercise in the heat in order to prevent the system from hyperthermia. Full article

(This article belongs to the Special Issue Human Thermophysiology)

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15 pages, 1569 KB

Open AccessEditor’s ChoiceArticle

Clostridioides difficile and Vancomycin-Resistant Enterococci in COVID-19 Patients with Severe Pneumonia

by Kateřina Bogdanová, Lenka Doubravská, Iva Vágnerová, Kristýna Hricová, Vendula Pudová, Magdaléna Röderová, Jan Papajk, Radovan Uvízl, Kateřina Langová and Milan Kolář

Life 2021, 11(11), 1127; https://doi.org/10.3390/life11111127 - 22 Oct 2021

Cited by 12 | Viewed by 3485

Abstract

Broad-spectrum antibiotics administered to patients with severe COVID-19 pneumonia pose a risk of infection caused by Clostridioides difficile. This risk is reduced mainly by strict hygiene measures and early de-escalation of antibiotic therapy. Recently, oral vancomycin prophylaxis (OVP) has also been discussed. [...] Read more.

Broad-spectrum antibiotics administered to patients with severe COVID-19 pneumonia pose a risk of infection caused by Clostridioides difficile. This risk is reduced mainly by strict hygiene measures and early de-escalation of antibiotic therapy. Recently, oral vancomycin prophylaxis (OVP) has also been discussed. This retrospective study aimed to assess the prevalence of C. difficile in critical COVID-19 patients staying in an intensive care unit of a tertiary hospital department of anesthesiology, resuscitation, and intensive care from November 2020 to May 2021 and the rates of vancomycin-resistant enterococci (VRE) after the introduction of OVP and to compare the data with those from controls in the pre-pandemic period (November 2018 to May 2019). During the COVID-19 pandemic, there was a significant increase in toxigenic C. difficile rates to 12.4% of patients, as compared with 1.6% in controls. The peak rates were noted in February 2021 (25% of patients), immediately followed by initiation of OVP, changes to hygiene precautions, and more rapid de-escalation of antibiotic therapy. Subsequently, toxigenic C. difficile detection rates started to fall. There was a nonsignificant increase in VRE detected in non-gastrointestinal tract samples to 8.9% in the COVID-19 group, as compared to 5.3% in the control group. Molecular analysis confirmed mainly clonal spread of VRE. Full article

(This article belongs to the Collection Bacterial Infections, Treatment and Antibiotic Resistance)

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12 pages, 282 KB

Open AccessEditor’s ChoiceReview

Using Telemedicine to Monitor the Patient with Chronic Respiratory Failure

by Nicolino Ambrosino and Paola Pierucci

Life 2021, 11(11), 1113; https://doi.org/10.3390/life11111113 - 20 Oct 2021

Cited by 13 | Viewed by 4433

Abstract

Background: Advances in management have improved mortality of individuals with chronic respiratory failure (CRF), leading to an increase in need for long-term oxygen therapy and/or ventilatory support. These individuals require frequent visits and monitoring of their physiological parameters as well as of [...] Read more.

Background: Advances in management have improved mortality of individuals with chronic respiratory failure (CRF), leading to an increase in need for long-term oxygen therapy and/or ventilatory support. These individuals require frequent visits and monitoring of their physiological parameters as well as of the functioning of their devices, such as ventilators or oxygen concentrators. Telemedicine is a clinical application of Information Communication Technology connecting patients to specialised care consultants. This narrative review aims to explore the current available telemonitoring options for individuals with CRF and reported or potential results. Methods: The research focused on EMBASE, CINALH, PubMed, and Scopus databases. Papers published between 2003 and 2021 in English were considered. Results: Different sensors, transmission devices and systems, and interventions are used with promising but not conclusive clinical results. However, legal problems are still unsolved, and economic advantages for health care systems, although potentially high, are still under debate. Conclusions: Telemonitoring systems for individuals with CRF are increasingly used; with promising results still to be clarified, legal, economical and organisational issues must be defined. Full article

(This article belongs to the Special Issue Utilizing Telemedicine as a Tool to Enhance Outcomes in Individuals with Chronic Respiratory Diseases)

15 pages, 1996 KB

Open AccessEditor’s ChoiceArticle

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 19 | Viewed by 4272

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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21 pages, 7336 KB

Open AccessEditor’s ChoiceReview

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 30 | Viewed by 11728

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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11 pages, 2104 KB

Open AccessEditor’s ChoiceArticle

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 7 | Viewed by 2773

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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9 pages, 1939 KB

Open AccessEditor’s ChoiceCommunication

Robust Neutralizing Antibody Responses 6 Months Post Vaccination with BNT162b2: A Prospective Study in 308 Healthy Individuals

by Evangelos Terpos, Vangelis Karalis, Ioannis Ntanasis-Stathopoulos, Maria Gavriatopoulou, Sentiljana Gumeni, Panagiotis Malandrakis, Eleni-Dimitra Papanagnou, Efstathios Kastritis, Ioannis P. Trougakos and Meletios A. Dimopoulos

Life 2021, 11(10), 1077; https://doi.org/10.3390/life11101077 - 12 Oct 2021

Cited by 24 | Viewed by 3295

Abstract

Elucidating long-term immunity following COVID-19 vaccination is essential for decision-making regarding booster shots. The aim of this study was to investigate the kinetics of neutralizing antibodies (Nabs) against SARS-CoV-2 up to six months after the second vaccination dose with the BNT162b2 mRNA vaccine. [...] Read more.

Elucidating long-term immunity following COVID-19 vaccination is essential for decision-making regarding booster shots. The aim of this study was to investigate the kinetics of neutralizing antibodies (Nabs) against SARS-CoV-2 up to six months after the second vaccination dose with the BNT162b2 mRNA vaccine. Nabs levels were measured on days 1 (before the first vaccine shot), 8, 22 (before the second shot), 36, 50, and 3 and 6 months after the second vaccination (NCT04743388). Three hundred and eight healthy individuals without malignant disease were included in this study. At six months, 2.59% of the participants had a Nabs value less than 30%, while 11.9% had Nabs values of less than 50%. Importantly, 58% of the subjects had Nabs values of more than 75%. Nabs were initially eliminated at a relatively slow rate, but after three months their elimination was 5.7 times higher. Older age was inversely associated with Nabs levels at all examined timepoints. Interestingly, a population modeling analysis estimated that half of the subjects will have Nabs values less than 73.8% and 64.6% at 9 and 12 months, respectively, post vaccination completion. In conclusion, we found a persistent but declining anti-SARS-CoV-2 humoral immunity at six months following full vaccination with BNT162b2 in healthy individuals, which was more pronounced among older persons. These data may inform the public health policies regarding the prioritization of booster vaccine shots. Full article

(This article belongs to the Special Issue Virology Applications to COVID-19 Pandemic)

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24 pages, 395 KB

Open AccessEditor’s ChoiceReview

Current Therapeutic Approach to Acute Myocardial Infarction in Patients with Congenital Hemophilia

by Minerva Codruta Badescu, Manuela Ciocoiu, Elena Rezus, Oana Viola Badulescu, Daniela Maria Tanase, Anca Ouatu, Nicoleta Dima, Ana Roxana Ganceanu-Rusu, Diana Popescu, Petronela Nicoleta Seritean Isac, Tudor-Marcel Genes and Ciprian Rezus

Life 2021, 11(10), 1072; https://doi.org/10.3390/life11101072 - 11 Oct 2021

Cited by 13 | Viewed by 3400

Abstract

Advances in the treatment of hemophilia have made the life expectancy of hemophiliacs similar to that of the general population. Physicians have begun to face age-related diseases not previously encountered in individuals with hemophilia. Treatment of acute myocardial infarction (AMI) is particularly challenging [...] Read more.

Advances in the treatment of hemophilia have made the life expectancy of hemophiliacs similar to that of the general population. Physicians have begun to face age-related diseases not previously encountered in individuals with hemophilia. Treatment of acute myocardial infarction (AMI) is particularly challenging because the therapeutic strategies influence both the patient’s thrombotic and hemorrhagic risk. As progress has been made in the treatment of AMI over the last decade, we performed an in-depth analysis of the available literature, highlighting the latest advances in the therapy of AMI in hemophiliacs. It is generally accepted that after the optimal substitution therapy has been provided, patients with hemophilia should be treated in the same way as those in the general population. New-generation stents that allow short dual antiplatelet therapy and potent P2Y₁₂ receptor inhibitors have begun to be successfully used. At a time when specific recommendations and relevant data are scarce, our study provides up-to-date information to physicians involved in the treatment of AMI in hemophiliacs. Full article

(This article belongs to the Special Issue Myocardial Infarction 2021)

13 pages, 2032 KB

Open AccessEditor’s ChoiceArticle

Sorafenib Combined with Chemoembolization for Locally Advanced Hepatocellular Carcinoma with Macroscopic Vascular Invasion: A Propensity Score Analysis

by Gun Ha Kim, Sang Lim Choi, Jin Hyoung Kim, Ju Hyun Shim, Meshari Alali and Nayoung Kim

Life 2021, 11(10), 1066; https://doi.org/10.3390/life11101066 - 10 Oct 2021

Cited by 6 | Viewed by 2448

Abstract

The purpose of this study was to compare the efficacy and safety of transarterial chemoembolization (TACE) plus sorafenib with those of TACE alone in patients with locally advanced hepatocellular carcinoma (HCC). Treatment-naïve patients with preserved hepatic reserve (Child–Pugh score ≤ 7) who received [...] Read more.

The purpose of this study was to compare the efficacy and safety of transarterial chemoembolization (TACE) plus sorafenib with those of TACE alone in patients with locally advanced hepatocellular carcinoma (HCC). Treatment-naïve patients with preserved hepatic reserve (Child–Pugh score ≤ 7) who received TACE plus sorafenib (n = 91) or TACE alone (n = 109) for locally advanced HCC with macrovascular invasion were retrospectively evaluated. Propensity score matching (PSM) was used to correct selection bias, and 63 pairs were created. In the entire study population, the median progression-free survival (PFS) and overall survival (OS) with TACE plus sorafenib were better than those with TACE alone. After PSM, the median PFS (7.0 vs. 4.3 months; p = 0.017) and OS (17.5 vs. 12.8 months; p = 0.049) were again significantly longer with TACE plus sorafenib than with TACE alone. Stratified Cox regression analysis and doubly robust estimation revealed that treatment type was significantly associated with both PFS and OS. In the subgroup analysis, TACE plus sorafenib did not show a significant survival benefit for patients with main portal vein or inferior vena cava invasion. Major complications were similar in both groups (p = 0.330). In conclusion, TACE plus sorafenib showed better survival outcomes than TACE alone in patients with locally advanced HCC. Full article

(This article belongs to the Special Issue Transarterial Chemoembolization for the Treatment of Hepatocellular Carcinoma)

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13 pages, 1361 KB

Open AccessEditor’s ChoiceReview

Cardiac Transplantation and the Use of Cannabis

by Hirak Shah, Meg Fraser, Arianne C. Agdamag, Valmiki Maharaj, Bellony Nzemenoh, Cindy M. Martin, Tamas Alexy and Daniel J. Garry

Life 2021, 11(10), 1063; https://doi.org/10.3390/life11101063 - 9 Oct 2021

Cited by 4 | Viewed by 3426

Abstract

Cardiac transplantation requires the careful allocation of a limited number of precious organs. Therefore, it is critical to select candidates that will receive the greatest anticipated medical benefit but will also serve as the best stewards of the organ. Individual transplant teams have [...] Read more.

Cardiac transplantation requires the careful allocation of a limited number of precious organs. Therefore, it is critical to select candidates that will receive the greatest anticipated medical benefit but will also serve as the best stewards of the organ. Individual transplant teams have established prerequisites pertaining to recreational drug, tobacco, alcohol, and controlled substance use in potential organ recipients and post-transplantation. Legalization of cannabis and implementation of its prescription-based use for the management of patients with chronic conditions have been increasing over the past years. Center requirements regarding abstinence from recreational and medical cannabis use vary due to rapidly changing state regulations, as well as the lack of clinical safety data in this population. This is evident by the results of the multicenter survey presented in this paper. Developing uniform guidelines around cannabis use will be imperative not only for providers but also for patients. Full article

(This article belongs to the Collection Heart Failure and Heart Transplantation)

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25 pages, 8146 KB

Open AccessEditor’s ChoiceReview

Depressive and Neurocognitive Disorders in the Context of the Inflammatory Background of COVID-19

by Eliza Dąbrowska, Beata Galińska-Skok and Napoleon Waszkiewicz

Life 2021, 11(10), 1056; https://doi.org/10.3390/life11101056 - 8 Oct 2021

Cited by 28 | Viewed by 4967

Abstract

The dysfunctional effects of the coronavirus disease 2019 (COVID-19) infection on the nervous system are established. The manifestation of neuropsychiatric symptoms during and after infection is influenced by the neuroinvasive and neurotrophic properties of SARS-CoV-2 as well as strong inflammation characterised by a [...] Read more.

The dysfunctional effects of the coronavirus disease 2019 (COVID-19) infection on the nervous system are established. The manifestation of neuropsychiatric symptoms during and after infection is influenced by the neuroinvasive and neurotrophic properties of SARS-CoV-2 as well as strong inflammation characterised by a specific “cytokine storm”. Research suggests that a strong immune response to a SARS-CoV-2 infection and psychological stressors related to the pandemic may cause chronic inflammatory processes in the body with elevated levels of inflammatory markers contributing to the intensification of neurodegenerative processes. It is suggested that neuroinflammation and associated central nervous system changes may significantly contribute to the etiopathogenesis of depressive disorders. In addition, symptoms after a COVID-19 infection may persist for up to several weeks after an acute infection as a post-COVID-19 syndrome. Moreover, previous knowledge indicates that among SSRI (selective serotonin reuptake inhibitor) group antidepressants, fluoxetine is a promising drug against COVID-19. In conclusion, further research, observation and broadening of the knowledge of the pathomechanism of a SARS-CoV-2 infection and the impact on potential complications are necessary. It is essential to continue research in order to assess the long-term neuropsychiatric effects in COVID-19 patients and to find new therapeutic strategies. Full article

(This article belongs to the Special Issue Depressive Disorders-New Challenges)

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18 pages, 3407 KB

Open AccessEditor’s ChoiceArticle

CXCR4-CCR7 Heterodimerization Is a Driver of Breast Cancer Progression

by Valentina Poltavets, Jessica W. Faulkner, Deepak Dhatrak, Robert J. Whitfield, Shaun R. McColl and Marina Kochetkova

Life 2021, 11(10), 1049; https://doi.org/10.3390/life11101049 - 7 Oct 2021

Cited by 7 | Viewed by 4341

Abstract

Metastatic breast cancer has one of the highest mortality rates among women in western society. Chemokine receptors CXCR4 and CCR7 have been shown to be linked to the metastatic spread of breast cancer, however, their precise function and underlying molecular pathways leading to [...] Read more.

Metastatic breast cancer has one of the highest mortality rates among women in western society. Chemokine receptors CXCR4 and CCR7 have been shown to be linked to the metastatic spread of breast cancer, however, their precise function and underlying molecular pathways leading to the acquisition of the pro-metastatic properties remain poorly understood. We demonstrate here that the CXCR4 and CCR7 receptor ligands, CXCL12 and CCL19, cooperatively bind and selectively elicit synergistic signalling responses in invasive breast cancer cell lines as well as primary mammary human tumour cells. Furthermore, for the first time, we have documented the presence of CXCR4-CCR7 heterodimers in advanced primary mammary mouse and human tumours where number of CXCR4-CCR7 complexes directly correlate with the severity of the disease. The functional significance of the CXCR4-CCR7 association was also demonstrated when their forced heterodimerization led to the acquisition of invasive phenotype in non-metastatic breast cancer cells. Taken together, our data establish the CXCR4-CCR7 receptor complex as a new functional unit, which is responsible for the acquisition of breast cancer cell metastatic phenotype and which may serve as a novel biomarker for invasive mammary tumours. Full article

(This article belongs to the Special Issue Chemokines and Their Receptors)

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12 pages, 541 KB

Open AccessEditor’s ChoiceReview

Is There a Link between COVID-19 Infection, Periodontal Disease and Acute Myocardial Infarction?

by Ioana-Patricia Rodean, Carmen-Ioana Biriș, Vasile-Bogdan Halațiu, Andrei Modiga, Luminița Lazăr, Imre Benedek and Theodora Benedek

Life 2021, 11(10), 1050; https://doi.org/10.3390/life11101050 - 7 Oct 2021

Cited by 12 | Viewed by 3675

Abstract

Both periodontal disease and atherosclerosis are chronic disorders with an inflammatory substrate that leads to alteration of the host’s immune response. In PD, inflammation is responsible for bone tissue destruction, while in atherosclerosis, it leads to atheromatous plaque formation. These modifications result from [...] Read more.

Both periodontal disease and atherosclerosis are chronic disorders with an inflammatory substrate that leads to alteration of the host’s immune response. In PD, inflammation is responsible for bone tissue destruction, while in atherosclerosis, it leads to atheromatous plaque formation. These modifications result from the action of pro-inflammatory cytokines that are secreted both locally at gingival or coronary sites, and systemically. Recently, it was observed that in patients with PD or with cardiovascular disease, COVID-19 infection is prone to be more severe. While the association between PD, inflammation and cardiovascular disease is well-known, the impact of COVID-19-related inflammation on the systemic complications of these conditions has not been established yet. The purpose of this review is to bring light upon the latest advances in understanding the link between periodontal–cardiovascular diseases and COVID-19 infection. Full article

(This article belongs to the Special Issue Myocardial Infarction 2021)

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21 pages, 4786 KB

Open AccessEditor’s ChoiceReview

The Structure, Activity, and Function of the SETD3 Protein Histidine Methyltransferase

by Apolonia Witecka, Sebastian Kwiatkowski, Takao Ishikawa and Jakub Drozak

Life 2021, 11(10), 1040; https://doi.org/10.3390/life11101040 - 2 Oct 2021

Cited by 12 | Viewed by 4885

Abstract

SETD3 has been recently identified as a long sought, actin specific histidine methyltransferase that catalyzes the Nτ-methylation reaction of histidine 73 (H73) residue in human actin or its equivalent in other metazoans. Its homologs are widespread among multicellular eukaryotes and expressed in [...] Read more.

SETD3 has been recently identified as a long sought, actin specific histidine methyltransferase that catalyzes the Nτ-methylation reaction of histidine 73 (H73) residue in human actin or its equivalent in other metazoans. Its homologs are widespread among multicellular eukaryotes and expressed in most mammalian tissues. SETD3 consists of a catalytic SET domain responsible for transferring the methyl group from S-adenosyl-L-methionine (AdoMet) to a protein substrate and a RuBisCO LSMT domain that recognizes and binds the methyl-accepting protein(s). The enzyme was initially identified as a methyltransferase that catalyzes the modification of histone H3 at K4 and K36 residues, but later studies revealed that the only bona fide substrate of SETD3 is H73, in the actin protein. The methylation of actin at H73 contributes to maintaining cytoskeleton integrity, which remains the only well characterized biological effect of SETD3. However, the discovery of numerous novel methyltransferase interactors suggests that SETD3 may regulate various biological processes, including cell cycle and apoptosis, carcinogenesis, response to hypoxic conditions, and enterovirus pathogenesis. This review summarizes the current advances in research on the SETD3 protein, its biological importance, and role in various diseases. Full article

(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)

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19 pages, 8963 KB

Open AccessEditor’s ChoiceReview

Anthropogenic Drivers Leading to Population Decline and Genetic Preservation of the Eurasian Griffon Vulture (Gyps fulvus)

by Monica Pirastru, Paolo Mereu, Laura Manca, Daniela Bebbere, Salvatore Naitana and Giovanni G. Leoni

Life 2021, 11(10), 1038; https://doi.org/10.3390/life11101038 - 1 Oct 2021

Cited by 9 | Viewed by 4654

Abstract

Human activities are having increasingly devastating effects on the health of marine and terrestrial ecosystems. Studying the adaptive responses of animal species to changes in their habitat can be useful in mitigating this impact. Vultures represent one of the most virtuous examples of [...] Read more.

Human activities are having increasingly devastating effects on the health of marine and terrestrial ecosystems. Studying the adaptive responses of animal species to changes in their habitat can be useful in mitigating this impact. Vultures represent one of the most virtuous examples of adaptation to human-induced environmental changes. Once dependent on wild ungulate populations, these birds have adapted to the epochal change resulting from the birth of agriculture and livestock domestication, maintaining their essential role as ecological scavengers. In this review, we retrace the main splitting events characterising the vultures’ evolution, with particular emphasis on the Eurasian griffon Gyps fulvus. We summarise the main ecological and behavioural traits of this species, highlighting its vulnerability to elements introduced into the habitat by humans. We collected the genetic information available to date, underlining their importance for improving the management of this species, as an essential tool to support restocking practices and to protect the genetic integrity of G. fulvus. Finally, we examine the difficulties in implementing a coordination system that allows genetic information to be effectively transferred into management programs. Until a linking network is established between scientific research and management practices, the risk of losing important wildlife resources remains high. Full article

(This article belongs to the Special Issue Evolutionary and Conservation Genetics)

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11 pages, 1266 KB

Open AccessEditor’s ChoiceArticle

Comparison of the Effect of Unfractionated Heparin and Enoxaparin Sodium at Different Doses on the Course of COVID-19-Associated Coagulopathy

by Oleksandr Oliynyk, Wojciech Barg, Anna Slifirczyk, Yanina Oliynyk, Serhij Dubrov, Vitaliy Gurianov and Marta Rorat

Life 2021, 11(10), 1032; https://doi.org/10.3390/life11101032 - 30 Sep 2021

Cited by 30 | Viewed by 3948

Abstract

Background: COVID-19-associated coagulopathy (CAC) exacerbates the course of coronavirus infection and contributes to increased mortality. Current recommendations for CAC treatment include the use of low-molecular weight heparins (LMWH) at prophylactic or therapeutic doses, as well as the use of unfractionated heparin (UFH). Methods: [...] Read more.

Background: COVID-19-associated coagulopathy (CAC) exacerbates the course of coronavirus infection and contributes to increased mortality. Current recommendations for CAC treatment include the use of low-molecular weight heparins (LMWH) at prophylactic or therapeutic doses, as well as the use of unfractionated heparin (UFH). Methods: A randomised, controlled trial enrolled 126 patients hospitalised in the intensive care unit with severe COVID-19 complicated by CAC. The effects of LMWH at preventive and therapeutic doses and UFH at therapeutic doses on mortality and intubation rates were compared. Results: The number of intubations and deaths showed no significant difference depending on the anticoagulant therapy used. However, multivariate logistic regression models revealed an increased risk of intubation (p = 0.026, odds ratio (OR) = 3.33, 95% confidence interval (CI) 1.15–9.59), and an increased risk of death (p = 0.046, OR = 3.01, 95% CI 1.02–8.90), for patients treated with LMWH at a prophylactic dose but not at a therapeutic dose as compared to patients treated with UFH when controlling for other risk factors. Conclusions: The use of unfractionated heparin in the treatment of COVID-19-associated coagulopathy seems to be more effective at reducing the risk of intubation and death than enoxaparin at prophylactic doses. Full article

(This article belongs to the Section Epidemiology)

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12 pages, 2729 KB

Open AccessEditor’s ChoiceArticle

NMR Reveals the Conformational Changes of Cytochrome C upon Interaction with Cardiolipin

by Jianhua Zhan, Guangqing Zhang, Xin Chai, Qinjun Zhu, Peng Sun, Bin Jiang, Xin Zhou, Xu Zhang and Maili Liu

Life 2021, 11(10), 1031; https://doi.org/10.3390/life11101031 - 30 Sep 2021

Cited by 9 | Viewed by 3253

Abstract

Conformational change of cytochrome c (cyt c) caused by interaction with cardiolipin (CL) is an important step during apoptosis, but the underlying mechanism is controversial. To comprehensively clarify the structural transformations of cyt c upon interaction with CL and avoid the unpredictable alias [...] Read more.

Conformational change of cytochrome c (cyt c) caused by interaction with cardiolipin (CL) is an important step during apoptosis, but the underlying mechanism is controversial. To comprehensively clarify the structural transformations of cyt c upon interaction with CL and avoid the unpredictable alias that might come from protein labeling or mutations, the conformation of purified yeast iso–1 cyt c with natural isotopic abundance in different contents of CL was measured by using NMR spectroscopy, in which the trimethylated group of the protein was used as a natural probe. The data demonstrate that cyt c has two partially unfolded conformations when interacted with CL: one with Fe–His33 coordination and the other with a penta–coordination heme. The Fe–His33 coordination conformation can be converted into a penta–coordination heme conformation in high content of CL. The structure of cyt c becomes partially unfolded with more exposed heme upon interaction with CL, suggesting that cyt c prefers a high peroxidase activity state in the mitochondria, which, in turn, makes CL easy to be oxidized, and causes the release of cyt c into the cytoplasm as a trigger in apoptosis. Full article

(This article belongs to the Special Issue Application of Nuclear Magnetic Resonance Method in Protein Research)

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19 pages, 2462 KB

Open AccessEditor’s ChoiceReview

Compendium of Plant-Specific CRISPR Vectors and Their Technical Advantages

by Anshu Alok, Hanny Chauhan, Santosh Kumar Upadhyay, Ashutosh Pandey, Jitendra Kumar and Kashmir Singh

Life 2021, 11(10), 1021; https://doi.org/10.3390/life11101021 - 28 Sep 2021

Cited by 35 | Viewed by 7457

Abstract

CRISPR/Cas mediated genome editing is a revolutionary approach for manipulating the plant genome. However, the success of this technology is highly dependent on selection of a specific vector and the other components. A plant-specific CRISPR/Cas vector usually consists of a Cas gene, target-specific [...] Read more.

CRISPR/Cas mediated genome editing is a revolutionary approach for manipulating the plant genome. However, the success of this technology is highly dependent on selection of a specific vector and the other components. A plant-specific CRISPR/Cas vector usually consists of a Cas gene, target-specific gRNA, leader sequence, selectable marker gene, precise promoters, and other accessories. It has always been challenging to select the specific vector for each study due to a lack of comprehensive information on CRISPR vectors in one place. Herein, we have discussed every technical aspect of various important elements that will be highly useful in vector selection and efficient editing of the desired plant genome. Various factors such as the promoter regulating the expression of Cas and gRNA, gRNA size, Cas variants, multicistronic gRNA, and vector backbone, etc. influence transformation and editing frequency. For example, the use of polycistronic tRNA-gRNA, and Csy4-gRNA has been documented to enhance the editing efficiency. Similarly, the selection of an efficient selectable marker is also a very important factor. Information on the availability of numerous variants of Cas endonucleases, such as Cas9, Cas12a, Cas12b, Casɸ, and CasMINI, etc., with diverse recognition specificities further broadens the scope of editing. The development of chimeric proteins such as Cas fused to cytosine or adenosine deaminase domain and modified reverse transcriptase using protein engineering enabled base and prime editing, respectively. In addition, the newly discovered Casɸ and CasMINI would increase the scope of genetic engineering in plants by being smaller Cas variants. All advancements would contribute to the development of various tools required for gene editing, targeted gene insertion, transcriptional activation/suppression, multiplexing, prime editing, base editing, and gene tagging. This review will serve as an encyclopedia for plant-specific CRISPR vectors and will be useful for researchers. Full article

(This article belongs to the Special Issue Research Advances in Plant Genomics)

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24 pages, 1723 KB

Open AccessEditor’s ChoiceReview

Microfluidic Platforms to Unravel Mysteries of Alzheimer’s Disease: How Far Have We Come?

by Pragya Prasanna, Shweta Rathee, Vedanabhatla Rahul, Debabrata Mandal, Macherla Sharath Chandra Goud, Pardeep Yadav, Susan Hawthorne, Ankur Sharma, Piyush Kumar Gupta, Shreesh Ojha, Niraj Kumar Jha, Chiara Villa and Saurabh Kumar Jha

Life 2021, 11(10), 1022; https://doi.org/10.3390/life11101022 - 28 Sep 2021

Cited by 17 | Viewed by 12711

Abstract

Alzheimer’s disease (AD) is a significant health concern with enormous social and economic impact globally. The gradual deterioration of cognitive functions and irreversible neuronal losses are primary features of the disease. Even after decades of research, most therapeutic options are merely symptomatic, and [...] Read more.

Alzheimer’s disease (AD) is a significant health concern with enormous social and economic impact globally. The gradual deterioration of cognitive functions and irreversible neuronal losses are primary features of the disease. Even after decades of research, most therapeutic options are merely symptomatic, and drugs in clinical practice present numerous side effects. Lack of effective diagnostic techniques prevents the early prognosis of disease, resulting in a gradual deterioration in the quality of life. Furthermore, the mechanism of cognitive impairment and AD pathophysiology is poorly understood. Microfluidics exploits different microscale properties of fluids to mimic environments on microfluidic chip-like devices. These miniature multichambered devices can be used to grow cells and 3D tissues in vitro, analyze cell-to-cell communication, decipher the roles of neural cells such as microglia, and gain insights into AD pathophysiology. This review focuses on the applications and impact of microfluidics on AD research. We discuss the technical challenges and possible solutions provided by this new cutting-edge technique to understand disease-associated pathways and mechanisms. Full article

(This article belongs to the Special Issue Multi-Omics for the Understanding of Brain Diseases)

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11 pages, 851 KB

Open AccessEditor’s ChoiceArticle

Reduced Plasma Ascorbate and Increased Proportion of Dehydroascorbic Acid Levels in Patients Undergoing Hemodialysis

by Yuta Doshida, Mitsuyo Itabashi, Takashi Takei, Yuka Takino, Ayami Sato, Wako Yumura, Naoki Maruyama and Akihito Ishigami

Life 2021, 11(10), 1023; https://doi.org/10.3390/life11101023 - 28 Sep 2021

Cited by 6 | Viewed by 4621

Abstract

Ascorbate functions as an electron donor and scavenges free radicals. Dehydroascorbic acid (DHA), the oxidized form of ascorbate, is generated as a result of these reactions. While low plasma ascorbate levels have been reported in hemodialysis patients worldwide, no studies have measured DHA [...] Read more.

Ascorbate functions as an electron donor and scavenges free radicals. Dehydroascorbic acid (DHA), the oxidized form of ascorbate, is generated as a result of these reactions. While low plasma ascorbate levels have been reported in hemodialysis patients worldwide, no studies have measured DHA because it is not generalized. In this study, we aimed to clarify whether plasma ascorbate levels are low in dialysis patients and whether plasma ascorbate levels fluctuate before and after dialysis. Moreover, we applied our previously established method to measure the plasma ascorbate and DHA levels in chronic kidney disease (CKD) stage G3–G5 non-hemodialysis-dependent patients, and pre- and post-dialysis plasma ascorbate and DHA levels in CKD stage G5D hemodialysis patients. The sample size was calculated using G-power software. The pre-dialysis plasma total ascorbate levels, including DHA, were significantly (56%) lower in hemodialysis patients than in non-hemodialysis-dependent CKD patients. After dialysis, there was a 40% reduction in the plasma total ascorbate levels. Hemodialysis increased the post-dialysis plasma proportions of DHA from 37% to 55%. The study results demonstrated lower plasma total ascorbate levels in hemodialysis patients compared with in non-hemodialysis-dependent CKD patients; these low levels in hemodialysis patients were further reduced by hemodialysis and increased DHA proportion. Full article

(This article belongs to the Special Issue Antimicrobial Mechanisms of Vitamin C)

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12 pages, 2240 KB

Open AccessEditor’s ChoiceArticle

A Novel Real-Time RT-PCR-Based Methodology for the Preliminary Typing of SARS-CoV-2 Variants, Employing Non-Extendable LNA Oligonucleotides and Three Signature Mutations at the Spike Protein Receptor-Binding Domain

by Serafeim C. Chaintoutis, Taxiarchis Chassalevris, Sofia Balaska, Evangelia Mouchtaropoulou, George Tsiolas, Ioannis Vlatakis, Areti Tychala, Dimitris Koutsioulis, Anagnostis Argiriou, Lemonia Skoura and Chrysostomos I. Dovas

Life 2021, 11(10), 1015; https://doi.org/10.3390/life11101015 - 27 Sep 2021

Cited by 7 | Viewed by 2999

Abstract

Mutations resulting in amino-acid substitutions of the SARS-CoV-2 spike protein receptor-binding domain (RBD) have been associated with enhanced transmissibility and immune escape of the respective variants, namely Alpha, Beta, Gamma or Delta. Rapid identification of the aforementioned variants of concern and their discrimination [...] Read more.

Mutations resulting in amino-acid substitutions of the SARS-CoV-2 spike protein receptor-binding domain (RBD) have been associated with enhanced transmissibility and immune escape of the respective variants, namely Alpha, Beta, Gamma or Delta. Rapid identification of the aforementioned variants of concern and their discrimination of other variants is thus of importance for public health interventions. For this reason, a one-step real-time RT-PCR assay employing four locked nucleic acid (LNA) modified TaqMan probes was developed, to target signature mutations associated with amino-acid substitutions at positions 478, 484 and 501 present in the receptor-binding motif (RBM) of the spike protein RBD. This region contains most contacting residues of SARS-CoV-2 that bind to ACE2. A novel strategy employing the use of non-extendable LNA oligonucleotide blockers that can reduce non-specific hybridization of probes increased the number of different mutated sites examined in a multiplex PCR. The combinatory analysis of the different fluorescence signals obtained enabled the preliminary differentiation of SARS-CoV-2 variants of concern. The assay is sensitive with a LOD of 263 copies/reaction for the Delta variant, 170 copies/reaction for the Beta variant, amplification efficiencies > 91% and a linear range of >5 log₁₀ copies/reaction against all targets. Validation of the assay using known SARS-CoV-2-positive and negative samples from humans and animals revealed its ability to correctly identify the targeted mutations and preliminary characterize the SARS-CoV-2 variants. The novel approach for mutation typing using LNA oligonucleotide blockers can be modified to target signature mutations at four different sites in the RBM and further expand the range of variants detected. Full article

(This article belongs to the Special Issue Virology Applications to COVID-19 Pandemic)

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13 pages, 19496 KB

Open AccessEditor’s ChoiceArticle

The Ginsenoside Rg₁ Rescues Mitochondrial Disorders in Aristolochic Acid-Induced Nephropathic Mice

by Chu-Kuang Chou, Yu-Shen Huang, Pei-Yu Lin, Kazuhiro Imai, Shih-Ming Chen and Jen-Ai Lee

Life 2021, 11(10), 1018; https://doi.org/10.3390/life11101018 - 27 Sep 2021

Cited by 3 | Viewed by 3273

Abstract

Chronic exposure to aristolochic acid (AA) leads to renal interstitial fibrosis and nephropathy. In this study, we aimed to investigate the renoprotective effects of Panax ginseng extract (GE) and ginsenoside saponin (GS) on AA-induced nephropathy (AAN) in mice. Eighty female C3H/He mice were [...] Read more.

Chronic exposure to aristolochic acid (AA) leads to renal interstitial fibrosis and nephropathy. In this study, we aimed to investigate the renoprotective effects of Panax ginseng extract (GE) and ginsenoside saponin (GS) on AA-induced nephropathy (AAN) in mice. Eighty female C3H/He mice were randomly divided into eight groups, including normal; AA (3 μg/mL for 56 days); AA with GE (125, 250, or 500 mg/kg/d for 14 days); and AA with important GE ingredients, Rg₁, Rb₁, or Rd (5 mg/kg/d for 14 days). Compared with the AA group, renal injuries were significantly decreased in the GE (250 mg/kg/d), Rb₁, and Rg₁ treatment groups. Rg₁ exhibited the best renoprotection among all GS-treated groups. There were 24 peaks significantly altered among normal, AA, and AA + Rg₁ groups, and four mitochondrial proteins were identified, including acyl-CoA synthetase medium-chain family member 2, upregulated during skeletal muscle growth 5 (Usmg5), mitochondrial aconitase 2 (ACO2), and cytochrome c oxidase subunit Va preprotein (COX5a). We demonstrated for the first time that the AAN mechanism and renoprotective effects of Rg₁ are associated with expression of mitochondrial proteins, especially ACO2, Usmg5, and COX5a. Full article

(This article belongs to the Section Plant Science)

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19 pages, 32478 KB

Open AccessEditor’s ChoiceArticle

COVID-19 and Antimicrobial Resistance: Data from the Greek Electronic System for the Surveillance of Antimicrobial Resistance—WHONET-Greece (January 2018–March 2021)

by Michalis Polemis, Georgia Mandilara, Olga Pappa, Athina Argyropoulou, Efstathia Perivolioti, Nikolaos Koudoumnakis, Spyros Pournaras, Alexandra Vasilakopoulou, Sophia Vourli, Helen Katsifa, Theodoros Karampatakis, Anastasia Papavasiliou, Efthymia Petinaki, Stylianos Xitsas, Lemonia Skoura, Efthymia Protonotariou, Paraskevi Mantzana, Konstantina Gartzonika, Efthalia Priavali, Amalia Kallinteri, Panagiota Giannopoulou, Nikoletta Charalampaki, Meletis Memezas, Zervaki Calina Oana, Marina Papadogianni, Maria Panopoulou, Athanasia Koutsidou, Alkiviadis Vatopoulos and Kyriaki Tryfinopoulou Show full author list Hide full author list

Life 2021, 11(10), 996; https://doi.org/10.3390/life11100996 - 22 Sep 2021

Cited by 46 | Viewed by 6012

Abstract

Changes in hospitals’ daily practice due to COVID-19 pandemic may have an impact on antimicrobial resistance (AMR). We aimed to assess this possible impact as captured by the Greek Electronic System for the Surveillance of Antimicrobial Resistance (WHONET-Greece). Routine susceptibility data of 17,837 [...] Read more.

Changes in hospitals’ daily practice due to COVID-19 pandemic may have an impact on antimicrobial resistance (AMR). We aimed to assess this possible impact as captured by the Greek Electronic System for the Surveillance of Antimicrobial Resistance (WHONET-Greece). Routine susceptibility data of 17,837 Gram-negative and Gram-positive bacterial isolates from blood and respiratory specimens of hospitalized patients in nine COVID-19 tertiary hospitals were used in order to identify potential differences in AMR trends in the last three years, divided into two periods, January 2018–March 2020 and April 2020–March 2021. Interrupted time-series analysis was used to evaluate differences in the trends of non-susceptibility before and after the changes due to COVID-19. We found significant differences in the slope of non-susceptibility trends of Acinetobacter baumannii blood and respiratory isolates to amikacin, tigecycline and colistin; of Klebsiella pneumoniae blood and respiratory isolates to meropenem and tigecycline; and of Pseudomonas aeruginosa respiratory isolates to imipenem, meropenem and levofloxacin. Additionally, we found significant differences in the slope of non-susceptibility trends of Staphylococcus aureus isolates to oxacillin and of Enterococcus faecium isolates to glycopeptides. Assessing in this early stage, through surveillance of routine laboratory data, the way a new global threat like COVID-19 could affect an already ongoing pandemic like AMR provides useful information for prompt action. Full article

(This article belongs to the Special Issue Ecology, Evolution and Epidemiology of Coronaviruses)

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13 pages, 2258 KB

Open AccessEditor’s ChoiceArticle

Narrow Precursor Mass Range for DIA–MS Enhances Protein Identification and Quantification in Arabidopsis

by Huoming Zhang and Dalila Bensaddek

Life 2021, 11(9), 982; https://doi.org/10.3390/life11090982 - 18 Sep 2021

Cited by 11 | Viewed by 4031

Abstract

Data independent acquisition–mass spectrometry (DIA–MS) is becoming widely utilised for robust and accurate quantification of samples in quantitative proteomics. Here, we describe the systematic evaluation of the effects of DIA precursor mass range on total protein identification and quantification. We show that a [...] Read more.

Data independent acquisition–mass spectrometry (DIA–MS) is becoming widely utilised for robust and accurate quantification of samples in quantitative proteomics. Here, we describe the systematic evaluation of the effects of DIA precursor mass range on total protein identification and quantification. We show that a narrow mass range of precursors (~250 m/z) for DIA–MS enables a higher number of protein identifications. Subsequent application of DIA with narrow precursor range (from 400 to 650 m/z) on an Arabidopsis sample with spike-in known proteins identified 34.7% more proteins than in conventional DIA (cDIA) with a wide precursor range of 400–1200 m/z. When combining several DIA–MS analyses with narrow precursor ranges (i.e., 400–650, 650–900 and 900–1200 m/z), we were able to quantify 10,099 protein groups with a median coefficient of variation of <6%. These findings represent a 54.7% increase in the number of proteins quantified than with cDIA analysis. This is particularly important for low abundance proteins, as exemplified by the six-protein mix spike-in. In cDIA only five out of the six-protein mix were quantified while our approach allowed accurate quantitation of all six proteins. Full article

(This article belongs to the Special Issue Plant Proteomics)

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14 pages, 2602 KB

Open AccessEditor’s ChoiceArticle

Sleep Apnea in Idiopathic Pulmonary Fibrosis: A Molecular Investigation in an Experimental Model of Fibrosis and Intermittent Hypoxia

by Liasmine Haine, Juliette Bravais, Céline-Hivda Yegen, Jean-Francois Bernaudin, Dominique Marchant, Carole Planès, Nicolas Voituron and Emilie Boncoeur

Life 2021, 11(9), 973; https://doi.org/10.3390/life11090973 - 15 Sep 2021

Cited by 8 | Viewed by 3337

Abstract

Background: High prevalence of obstructive sleep apnea (OSA) is reported in incident and prevalent forms of idiopathic pulmonary fibrosis (IPF). We previously reported that Intermittent Hypoxia (IH), the major pathogenic element of OSA, worsens experimental lung fibrosis. Our objective was to investigate the [...] Read more.

Background: High prevalence of obstructive sleep apnea (OSA) is reported in incident and prevalent forms of idiopathic pulmonary fibrosis (IPF). We previously reported that Intermittent Hypoxia (IH), the major pathogenic element of OSA, worsens experimental lung fibrosis. Our objective was to investigate the molecular mechanisms involved. Methods: Impact of IH was evaluated on C57BL/6J mice developing lung fibrosis after intratracheal instillation of Bleomycin (BLM). Mice were Pre-exposed 14 days to IH before induction of lung fibrosis or Co-challenged with IH and BLM for 14 days. Weight loss and survival were daily monitored. After experimentations, lungs were sampled for histology, and protein and RNA were extracted. Results: Co-challenge or Pre-exposure of IH and BLM induced weight loss, increased tissue injury and collagen deposition, and pro-fibrotic markers. Major worsening effects of IH exposure on lung fibrosis were observed when mice were Pre-exposed to IH before developing lung fibrosis with a strong increase in sXBP1 and ATF6N ER stress markers. Conclusion: Our results showed that IH exacerbates BLM-induced lung fibrosis more markedly when IH precedes lung fibrosis induction, and that this is associated with an enhancement of ER stress markers. Full article

(This article belongs to the Special Issue Cellular and Functional Response to Hypoxia)

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20 pages, 6851 KB

Open AccessEditor’s ChoiceArticle

Exploring the Impact of Terminators on Transgene Expression in Chlamydomonas reinhardtii with a Synthetic Biology Approach

by Katrin Geisler, Mark A. Scaife, Paweł M. Mordaka, Andre Holzer, Eleanor V. Tomsett, Payam Mehrshahi, Gonzalo I. Mendoza Ochoa and Alison G. Smith

Life 2021, 11(9), 964; https://doi.org/10.3390/life11090964 - 14 Sep 2021

Cited by 9 | Viewed by 4631

Abstract

Chlamydomonas reinhardtii has many attractive features for use as a model organism for both fundamental studies and as a biotechnological platform. Nonetheless, despite the many molecular tools and resources that have been developed, there are challenges for its successful engineering, in particular to [...] Read more.

Chlamydomonas reinhardtii has many attractive features for use as a model organism for both fundamental studies and as a biotechnological platform. Nonetheless, despite the many molecular tools and resources that have been developed, there are challenges for its successful engineering, in particular to obtain reproducible and high levels of transgene expression. Here we describe a synthetic biology approach to screen several hundred independent transformants using standardised parts to explore different parameters that might affect transgene expression. We focused on terminators and, using a standardised workflow and quantitative outputs, tested 9 different elements representing three different size classes of native terminators to determine their ability to support high level expression of a GFP reporter gene. We found that the optimal size reflected the median size of element found in the C. reinhardtii genome. The behaviour of the terminator parts was similar with different promoters, in different host strains and with different transgenes. This approach is applicable to the systematic testing of other genetic elements, facilitating comparison to determine optimal transgene design. Full article

(This article belongs to the Special Issue Plant Synthetic Biology)

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22 pages, 5041 KB

Open AccessEditor’s ChoiceReview

Roles and Mechanisms of Deubiquitinases (DUBs) in Breast Cancer Progression and Targeted Drug Discovery

by Sixuan Li, Hongquan Zhang and Xiaofan Wei

Life 2021, 11(9), 965; https://doi.org/10.3390/life11090965 - 14 Sep 2021

Cited by 10 | Viewed by 4632

Abstract

Deubiquitinase (DUB) is an essential component in the ubiquitin—proteasome system (UPS) by removing ubiquitin chains from substrates, thus modulating the expression, activity, and localization of many proteins that contribute to tumor development and progression. DUBs have emerged as promising prognostic indicators and drug [...] Read more.

Deubiquitinase (DUB) is an essential component in the ubiquitin—proteasome system (UPS) by removing ubiquitin chains from substrates, thus modulating the expression, activity, and localization of many proteins that contribute to tumor development and progression. DUBs have emerged as promising prognostic indicators and drug targets. DUBs have shown significant roles in regulating breast cancer growth, metastasis, resistance to current therapies, and several canonical oncogenic signaling pathways. In addition, specific DUB inhibitors have been identified and are expected to benefit breast cancer patients in the future. Here, we review current knowledge about the effects and molecular mechanisms of DUBs in breast cancer, providing novel insight into treatments of breast cancer-targeting DUBs. Full article

(This article belongs to the Collection Tumor Progression, Microenvironments, and Therapeutics)

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22 pages, 2454 KB

Open AccessEditor’s ChoiceReview

Structure, Activity and Function of the Protein Arginine Methyltransferase 6

by Somlee Gupta, Rajashekar Varma Kadumuri, Anjali Kumari Singh, Sreenivas Chavali and Arunkumar Dhayalan

Life 2021, 11(9), 951; https://doi.org/10.3390/life11090951 - 11 Sep 2021

Cited by 26 | Viewed by 5435

Abstract

Members of the protein arginine methyltransferase (PRMT) family methylate the arginine residue(s) of several proteins and regulate a broad spectrum of cellular functions. Protein arginine methyltransferase 6 (PRMT6) is a type I PRMT that asymmetrically dimethylates the arginine residues of numerous substrate proteins. [...] Read more.

Members of the protein arginine methyltransferase (PRMT) family methylate the arginine residue(s) of several proteins and regulate a broad spectrum of cellular functions. Protein arginine methyltransferase 6 (PRMT6) is a type I PRMT that asymmetrically dimethylates the arginine residues of numerous substrate proteins. PRMT6 introduces asymmetric dimethylation modification in the histone 3 at arginine 2 (H3R2me2a) and facilitates epigenetic regulation of global gene expression. In addition to histones, PRMT6 methylates a wide range of cellular proteins and regulates their functions. Here, we discuss (i) the biochemical aspects of enzyme kinetics, (ii) the structural features of PRMT6 and (iii) the diverse functional outcomes of PRMT6 mediated arginine methylation. Finally, we highlight how dysregulation of PRMT6 is implicated in various types of cancers and response to viral infections. Full article

(This article belongs to the Special Issue Structure, Activity, and Function of Protein Methyltransferases)

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14 pages, 2017 KB

Open AccessEditor’s ChoiceArticle

Hesperidin and Chlorogenic Acid Synergistically Inhibit the Growth of Breast Cancer Cells via Estrogen Receptor/Mitochondrial Pathway

by Pang-Hung Hsu, Wei-Hsuan Chen, Chen Juan-Lu, Shu-Chen Hsieh, Shih-Chao Lin, Ru-Tsun Mai and Shiow-Yi Chen

Life 2021, 11(9), 950; https://doi.org/10.3390/life11090950 - 10 Sep 2021

Cited by 35 | Viewed by 4963

Abstract

Breast cancer is the most common cancer in women worldwide. Hesperidin (Hes) and chlorogenic acid (CA) are traditional medicinal molecules that abundantly exist in natural plants or foods. These compounds have been shown to prevent and suppress various cancers and therefore can be [...] Read more.

Breast cancer is the most common cancer in women worldwide. Hesperidin (Hes) and chlorogenic acid (CA) are traditional medicinal molecules that abundantly exist in natural plants or foods. These compounds have been shown to prevent and suppress various cancers and therefore can be utilized as adjunctive therapies to aid cancer treatment. Here, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays show a greater synergistic inhibitory effect on the growth of breast cancer cells, MCF-7, but not normal breast cells, MCF-10A, than hesperidin or chlorogenic acid alone. We present the possible molecular signaling pathways in MCF-7 cells with or without herbal molecule treatments via proteomic approaches. The data were further analyzed by Ingenuity Pathway Analysis (IPA) and confirmed by quantifying mRNA associated with the estrogen-receptor signaling pathway and mitochondrial functions. We demonstrated that the expression of CYC1, TFAM, ATP5PB, mtATP6, mtDNA, and NRF-1 were decreased upon 12 h treatment, and subsequent ATP production was also significantly decreased at 24 h. These results identified a synergistic effect induced by combinational treatment with hesperidin and chlorogenic acid, which can regulate mitochondria and ATP production through the estrogen receptor pathway in MCF-7 cells. However, none of the treatments induced the generation of reactive oxygen species (ROS), suggesting that ROS likely plays no role in the observed pharmacological activities. Overall, our study sheds light on the adequacy of hesperidin and chlorogenic acid to serve as an adjunctive therapy when co-administrated with chemotherapy drugs in breast cancer patients. Full article

(This article belongs to the Special Issue Regulation of Natural Products to Immunity)

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10 pages, 1536 KB

Open AccessEditor’s ChoiceArticle

Evolution of Thyroglobulin Loop Kinetics in EpCAM

by Serena H. Chen and David R. Bell

Life 2021, 11(9), 915; https://doi.org/10.3390/life11090915 - 3 Sep 2021

Cited by 5 | Viewed by 2770

Abstract

Epithelial cell-activating molecule (EpCAM) is an important cancer biomarker and therapeutic target given its elevated expression in epithelial cancers. EpCAM is a type I transmembrane protein that forms cis-dimers along the thyroglobulin type-1A-like domain (TYD) in the extracellular region. The thyroglobulin loop [...] Read more.

Epithelial cell-activating molecule (EpCAM) is an important cancer biomarker and therapeutic target given its elevated expression in epithelial cancers. EpCAM is a type I transmembrane protein that forms cis-dimers along the thyroglobulin type-1A-like domain (TYD) in the extracellular region. The thyroglobulin loop (TY loop) within the TYD is structurally dynamic in the monomer state of human EpCAM, binding reversibly to a TYD site. However, it is not known if this flexibility is prevalent across different species. Here, we conduct over 17 μs of all-atom molecular dynamics simulations to study EpCAM TY loop kinetics of five different species, including human, mouse, chicken, frog, and fish. We find that the TY loop remains dynamic across evolution. In addition to the TYD binding site, we discover a second binding site for the TY loop in the C-terminal domain (CTD). Calculations of the dissociation rate constants from the simulation trajectories suggest a differential binding pattern of fish EpCAM and other organisms. Whereas fish TY loop has comparable binding for both TYD and CTD sites, the TY loops of other species preferably bind the TYD site. A hybrid construct of fish EpCAM with human TY loop restores the TYD binding preference, suggesting robust effects of the TY loop sequence on its dynamic behavior. Our findings provide insights into the structural dynamics of EpCAM and its implication in physiological functions. Full article

(This article belongs to the Special Issue Computational Modeling of Kinetics in Biological Systems)

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16 pages, 348 KB

Open AccessEditor’s ChoiceReview

Laparoscopy in Emergency: Why Not? Advantages of Laparoscopy in Major Emergency: A Review

by Giuseppe Ietto, Francesco Amico, Giuseppe Pettinato, Valentina Iori and Giulio Carcano

Life 2021, 11(9), 917; https://doi.org/10.3390/life11090917 - 3 Sep 2021

Cited by 16 | Viewed by 5458

Abstract

A laparoscopic approach is suggested with the highest grade of recommendation for acute cholecystitis, perforated gastroduodenal ulcers, acute appendicitis, gynaecological disorders, and non-specific abdominal pain (NSAP). To date, the main qualities of laparoscopy for these acute surgical scenarios are clearly stated: quicker surgery, [...] Read more.

A laparoscopic approach is suggested with the highest grade of recommendation for acute cholecystitis, perforated gastroduodenal ulcers, acute appendicitis, gynaecological disorders, and non-specific abdominal pain (NSAP). To date, the main qualities of laparoscopy for these acute surgical scenarios are clearly stated: quicker surgery, faster recovery and shorter hospital stay. For the remaining surgical emergencies, as well as for abdominal trauma, the role of laparoscopy is still a matter of debate. Patients might benefit from a laparoscopic approach only if performed by experienced teams and surgeons which guarantee a high standard of care. More precisely, laparoscopy can limit damage to the tissue and could be effective for the reduction of the overall amount of cell debris, which is a result of the intensity with which the immune system reacts to the injury and the following symptomatology. In fact, these fragments act as damage-associated molecular patterns (DAMPs). DAMPs, as well as pathogen associated molecular patterns (PAMPs), are recognised by both surface and intracellular receptors of the immune cells and activate the cascade which, in critically ill surgical patients, is responsible for a deranged response. This may result in the development of progressive and multiple organ dysfunctions, manifesting with acute respiratory distress syndrome (ARDS), coagulopathy, liver dysfunction and renal failure. In conclusion, none of the emergency surgical scenarios preclude laparoscopy, provided that the surgical tactic could ensure sufficient cleaning of the abdomen in addition to resolving the initial tissue damage caused by the “trauma”. Full article

(This article belongs to the Special Issue Trauma and Emergency: Beyond Damage Control Surgery)

16 pages, 880 KB

Open AccessEditor’s ChoiceReview

Elevation Mechanisms and Diagnostic Consideration of Cardiac Troponins under Conditions Not Associated with Myocardial Infarction. Part 1

by Aleksey M. Chaulin

Life 2021, 11(9), 914; https://doi.org/10.3390/life11090914 - 2 Sep 2021

Cited by 46 | Viewed by 7807

Abstract

Although cardiac troponins are considered the most specific biomarkers for the diagnosis of acute myocardial infarction (AMI), their diagnostic consideration goes far beyond the detection of this dangerous disease. The mechanisms of cardiac troponin elevation are extremely numerous and not limited to ischemic [...] Read more.

Although cardiac troponins are considered the most specific biomarkers for the diagnosis of acute myocardial infarction (AMI), their diagnostic consideration goes far beyond the detection of this dangerous disease. The mechanisms of cardiac troponin elevation are extremely numerous and not limited to ischemic necrosis of cardiac myocytes. Practitioners should be well aware of the underlying pathological and physiological conditions that can lead to elevated serum levels of cardiac troponins to avoid differential diagnostic errors, which will be greatly increased if clinicians rely on laboratory data alone. This article presents a classification of the main causes of an elevation in cardiac troponins and discusses in detail the mechanisms of such elevation and the diagnostic consideration of cardiac troponins in some conditions not associated with AMI, such as physical exertion, inflammatory heart diseases (myocarditis and endocarditis), pulmonary embolism (PE), renal failure, and systemic inflammation (sepsis). Full article

(This article belongs to the Special Issue Myocardial Infarction 2021)

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14 pages, 1088 KB

Open AccessEditor’s ChoiceReview

3D Printing—A Cutting Edge Technology for Treating Post-Infarction Patients

by Daniel Cernica, Imre Benedek, Stefania Polexa, Cosmin Tolescu and Theodora Benedek

Life 2021, 11(9), 910; https://doi.org/10.3390/life11090910 - 1 Sep 2021

Cited by 5 | Viewed by 4937

Abstract

The increasing complexity of cardiovascular interventions requires advanced peri-procedural imaging and tailored treatment. Three-dimensional printing technology represents one of the most significant advances in the field of cardiac imaging, interventional cardiology or cardiovascular surgery. Patient-specific models may provide substantial information on intervention planning [...] Read more.

The increasing complexity of cardiovascular interventions requires advanced peri-procedural imaging and tailored treatment. Three-dimensional printing technology represents one of the most significant advances in the field of cardiac imaging, interventional cardiology or cardiovascular surgery. Patient-specific models may provide substantial information on intervention planning in complex cardiovascular diseases, and volumetric medical imaging from CT or MRI can be translated into patient-specific 3D models using advanced post-processing applications. 3D printing and additive manufacturing have a great variety of clinical applications targeting anatomy, implants and devices, assisting optimal interventional treatment and post-interventional evaluation. Although the 3D printing technology still lacks scientific evidence, its benefits have been shown in structural heart diseases as well as for treatment of complex arrhythmias and corrective surgery interventions. Recent development has enabled transformation of conventional 3D printing into complex 3D functional living tissues contributing to regenerative medicine through engineered bionic materials such hydrogels, cell suspensions or matrix components. This review aims to present the most recent clinical applications of 3D printing in cardiovascular medicine, highlighting also the potential for future development of this revolutionary technology in the medical field. Full article

(This article belongs to the Section Medical Research)

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12 pages, 2342 KB

Open AccessEditor’s ChoiceArticle

Temperate Air Breathing Increases Cycling Performance in Hot and Humid Climate Environment

by Clovis Chabert, Aurélie Collado and Olivier Hue

Life 2021, 11(9), 911; https://doi.org/10.3390/life11090911 - 1 Sep 2021

Cited by 1 | Viewed by 2884

Abstract

Practicing physical activity in a hot and humid climate (HHC) is becoming increasingly common due to anthropogenic climate change and the growing number of international sports events held in warm countries. The aim of this study was to understand the physiological and psychological [...] Read more.

Practicing physical activity in a hot and humid climate (HHC) is becoming increasingly common due to anthropogenic climate change and the growing number of international sports events held in warm countries. The aim of this study was to understand the physiological and psychological effects of breathing two air temperatures during cycling exercise in HHC. Ten male athletes performed two sessions of exercise in HHC (T°: 32.0 ± 0.5 °C, relative humidity: 78.6 ± 0.7%) during which they breathed hot air (HA, 33.2 ± 0.06 °C) or temperate air (TA, 22.6 ± 0.1 °C). Each session was composed of 30 min of pre-fatigue cycling at constant intensity, followed by a 10 min self-regulated performance. During pre-fatigue, TA induced a better feeling score and a lower rating of perceived effort (respectively, +0.9 ± 0.2, p < 0.05; 1.13 ± 0.21; p < 0.05) with no changes in physiological parameters. During performance, oxygen consumption and mechanical workload were increased by TA (respectively, +0.23 ± 0.1 L min⁻¹, p < 0.05 and +19.2 ± 6.1 W, p < 0.01), whereas no significant differences were observed for psychological parameters. Reducing the breathed air temperature decreased the discomfort induced by HHC during exercise and increased the performance capacity during self-regulated exercise. Thus, breathed air temperature perception is linked to the hardship of training sessions and directly contributes to the performance decrease in HHC. Full article

(This article belongs to the Special Issue Human Thermophysiology)

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21 pages, 758 KB

Open AccessEditor’s ChoiceReview

Influencing Factors and Molecular Pathogenesis of Sarcopenia and Osteosarcopenia in Chronic Liver Disease

by Chisato Saeki and Akihito Tsubota

Life 2021, 11(9), 899; https://doi.org/10.3390/life11090899 - 30 Aug 2021

Cited by 25 | Viewed by 5087

Abstract

The liver plays a pivotal role in nutrient/energy metabolism and storage, anabolic hormone regulation, ammonia detoxification, and cytokine production. Impaired liver function can cause malnutrition, hyperammonemia, and chronic inflammation, leading to an imbalance between muscle protein synthesis and proteolysis. Patients with chronic liver [...] Read more.

The liver plays a pivotal role in nutrient/energy metabolism and storage, anabolic hormone regulation, ammonia detoxification, and cytokine production. Impaired liver function can cause malnutrition, hyperammonemia, and chronic inflammation, leading to an imbalance between muscle protein synthesis and proteolysis. Patients with chronic liver disease (CLD) have a high prevalence of sarcopenia, characterized by progressive loss of muscle mass and function, affecting health-related quality of life and prognosis. Recent reports have revealed that osteosarcopenia, defined as the concomitant occurrence of sarcopenia and osteoporosis, is also highly prevalent in patients with CLD. Since the differentiation and growth of muscles and bones are closely interrelated through mechanical and biochemical communication, sarcopenia and osteoporosis often progress concurrently and affect each other. Osteosarcopenia further exacerbates unfavorable health outcomes, such as vertebral fracture and frailty. Therefore, a comprehensive assessment of sarcopenia, osteoporosis, and osteosarcopenia, and an understanding of the pathogenic mechanisms involving the liver, bones, and muscles, are important for prevention and treatment. This review summarizes the molecular mechanisms of sarcopenia and osteosarcopenia elucidated to data in hopes of promoting advances in treating these musculoskeletal disorders in patients with CLD. Full article

(This article belongs to the Special Issue New Mechanism and Insights into Sarcopenia)

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11 pages, 565 KB

Open AccessEditor’s ChoiceArticle

Metabolic Constellations, Clusters, and Renal Function: Findings from the 2013–2018 National Health and Nutrition Examination Surveys

by Kathleen E. Adair, Kelly R. Ylitalo, Jeffrey S. Forsse, LesLee K. Funderburk and Rodney G. Bowden

Life 2021, 11(9), 904; https://doi.org/10.3390/life11090904 - 30 Aug 2021

Cited by 2 | Viewed by 2473

Abstract

Metabolic syndrome (MetS) is associated with decreased renal function and chronic kidney disease (CKD). To date, no research regarding the sixteen possible constellations resulting in the diagnosis of MetS has been elucidated. The purpose of this study is to report renal function in [...] Read more.

Metabolic syndrome (MetS) is associated with decreased renal function and chronic kidney disease (CKD). To date, no research regarding the sixteen possible constellations resulting in the diagnosis of MetS has been elucidated. The purpose of this study is to report renal function in sixteen metabolic constellations grouped into four metabolic clusters. Individuals (n = 2767; representing 86,652,073 individuals) from the 2013–2018 National Health and Nutrition Examination Surveys who met the criteria for MetS were included. Sixteen possible constellations of three or more risk factors were analyzed for renal function. Four metabolic clusters representing MetS with hyperglycemia (Cluster I), MetS with hypertension (Cluster II), MetS with hyperglycemia and hypertension (Cluster III), or MetS with normoglycemia and normotension (Cluster IV) were assessed for renal function and CKD status. Cluster III had the highest odds of CKD (OR = 2.57, 95% CL = 1.79, 3.68). Clusters II and III had the lowest renal function and were not different from one another (87.82 and 87.28 mL/min/1.73 m², p = 0.71). The constellation with the lowest renal function consisted of hypertension, high triglycerides, and a large waist circumference (82.86 mL/min/1.73 m²), whereas the constellation with the highest renal function consisted of hyperglycemia, low HDL, and a large waist circumference (107.46 mL/min/1.73 m²). The sixteen constellations of MetS do not have the same effects on renal function. More research is needed to understand the relationship between the various iterations of MetS and renal function. Full article

(This article belongs to the Collection Research Updates in Chronic Kidney Disease)

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12 pages, 603 KB

Open AccessEditor’s ChoiceBrief Report

BNT162b2 SARS-CoV-2 Vaccination Elicits High Titers of Neutralizing Antibodies to Both B.1 and P.1 Variants in Previously Infected and Uninfected Subjects

by Ilaria Vicenti, Francesca Gatti, Renzo Scaggiante, Adele Boccuto, Daniela Zago, Monica Basso, Filippo Dragoni, Saverio Giuseppe Parisi and Maurizio Zazzi

Life 2021, 11(9), 896; https://doi.org/10.3390/life11090896 - 29 Aug 2021

Cited by 2 | Viewed by 2832

Abstract

We aimed to investigate neutralizing antibody titers (NtAbT) to the P.1 and B.1 SARS-CoV-2 variants in a cohort of healthy health care workers (HCW), including 20 previously infected individuals tested at baseline (BL_inf, after a median of 298 days from diagnosis) [...] Read more.

We aimed to investigate neutralizing antibody titers (NtAbT) to the P.1 and B.1 SARS-CoV-2 variants in a cohort of healthy health care workers (HCW), including 20 previously infected individuals tested at baseline (BL_inf, after a median of 298 days from diagnosis) and 21 days after receiving one vaccine dose (D1_inf) and 15 uninfected subjects tested 21 days after the second-dose vaccination (D2_uninf). All the subjects received BNT162b2 vaccination. D1_inf NtAbT increased significantly with respect to BL_inf against both B.1 and P.1 variants, with a fold-change significantly higher for P.1. D1_inf NtAbT were significantly higher than D2_uninf NtAbT, against B.1 and P.1. NtAbT against the two strains were highly correlated. P.1 NtAbT were significantly higher than B.1 NtAbT. This difference was significant for post-vaccination sera in infected and uninfected subjects. A single-dose BNT162b2 vaccination substantially boosted the NtAb response to both variants in the previously infected subjects. NtAb titers to B.1 and P.1 lineages were highly correlated, suggesting substantial cross-neutralization. Higher titers to the P.1 than to the B.1 strain were driven by the post-vaccination titers, highlighting that cross-neutralization can be enhanced by vaccination. Full article

(This article belongs to the Special Issue Advances in Immunology of Infectious Diseases)

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12 pages, 1188 KB

Open AccessEditor’s ChoiceReview

Horizontal Gene Transfers in Plants

by Emilie Aubin, Moaine El Baidouri and Olivier Panaud

Life 2021, 11(8), 857; https://doi.org/10.3390/life11080857 - 21 Aug 2021

Cited by 25 | Viewed by 8040

Abstract

In plants, as in all eukaryotes, the vertical transmission of genetic information through reproduction ensures the maintenance of the integrity of species. However, many reports over the past few years have clearly shown that horizontal gene transfers, referred to as HGTs (the interspecific [...] Read more.

In plants, as in all eukaryotes, the vertical transmission of genetic information through reproduction ensures the maintenance of the integrity of species. However, many reports over the past few years have clearly shown that horizontal gene transfers, referred to as HGTs (the interspecific transmission of genetic information across reproductive barriers) are very common in nature and concern all living organisms including plants. The advent of next-generation sequencing technologies (NGS) has opened new perspectives for the study of HGTs through comparative genomic approaches. In this review, we provide an up-to-date view of our current knowledge of HGTs in plants. Full article

(This article belongs to the Collection Feature Review Papers for Life)

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12 pages, 2672 KB

Open AccessEditor’s ChoiceArticle

Gomisin L1, a Lignan Isolated from Schisandra Berries, Induces Apoptosis by Regulating NADPH Oxidase in Human Ovarian Cancer Cells

by Young Hyun Ko, Miran Jeong, Dae Sik Jang and Jung-Hye Choi

Life 2021, 11(8), 858; https://doi.org/10.3390/life11080858 - 21 Aug 2021

Cited by 11 | Viewed by 3530

Abstract

The fruits of Schisandra chinensis (Schisandra berries) are used as health food supplements and popular food ingredients in East Asia. Lignans, major and characteristic polyphenol compounds of Schisandra berries, possess various biological activities, including hepatoprotective and anticancer effects. However, the biological activities of [...] Read more.

The fruits of Schisandra chinensis (Schisandra berries) are used as health food supplements and popular food ingredients in East Asia. Lignans, major and characteristic polyphenol compounds of Schisandra berries, possess various biological activities, including hepatoprotective and anticancer effects. However, the biological activities of gomisin L1, a lignan isolated from Schisandra berries, are less to be investigated. In this study, the antitumor activity of gomisin L1 and its underlying molecular mechanism in human ovarian cancer cells were investigated. Gomisin L1 exhibited potent cytotoxic activity against A2780 and SKOV3 ovarian cancer cells. Flow cytometry analysis revealed that the growth inhibitory effects of gomisin L1 were mediated by the induction of apoptosis. Furthermore, gomisin L1 induced an increase in intracellular reactive oxygen species (ROS) levels, and the antioxidant N-acetyl cysteine significantly negated gomisin L1-induced cell death. Moreover, inhibition of NADPH oxidase (NOX) using an inhibitor and siRNA attenuated gomisin L1-induced death of, and ROS production in, human ovarian cancer cells. Taken together, these data indicate that the lignan gomisin L1 from Schisandra berries induces apoptotic cell death by regulating intracellular ROS production via NOX. Full article

(This article belongs to the Special Issue Bioactive Natural Compounds for Pharmaceutical and Nutraceutical Applications)

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11 pages, 992 KB

Open AccessEditor’s ChoiceHypothesis

Evaluating the Microbial Habitability of Rogue Planets and Proposing Speculative Scenarios on How They Might Act as Vectors for Panspermia

by Dirk Schulze-Makuch and Alberto G. Fairén

Life 2021, 11(8), 833; https://doi.org/10.3390/life11080833 - 14 Aug 2021

Cited by 3 | Viewed by 5159

Abstract

There are two types of rogue planets, sub-brown dwarfs and “rocky” rogue planets. Sub-brown dwarfs are unlikely to be habitable or even host life, but rocky rogue planets may have a liquid ocean under a thick atmosphere or an ice layer. If they [...] Read more.

There are two types of rogue planets, sub-brown dwarfs and “rocky” rogue planets. Sub-brown dwarfs are unlikely to be habitable or even host life, but rocky rogue planets may have a liquid ocean under a thick atmosphere or an ice layer. If they are overlain by an insulating ice layer, they are also referred to as Steppenwolf planets. However, given the poor detectability of rocky rogue planets, there is still no direct evidence of the presence of water or ice on them. Here we discuss the possibility that these types of rogue planets could harbor unicellular organisms, conceivably based on a variety of different energy sources, including chemical, osmotic, thermal, and luminous energy. Further, given the theoretically predicted high number of rogue planets in the galaxy, we speculate that rogue planets could serve as a source for galactic panspermia, transferring life to other planetary systems. Full article

(This article belongs to the Collection Feature Review Papers for Life)

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18 pages, 696 KB

Open AccessEditor’s ChoiceSystematic Review

Association between Diet Quality and Sarcopenia in Older Adults: Systematic Review of Prospective Cohort Studies

by Eun-Hee Jang, Ye-Ji Han, Seong-Eun Jang and Seungmin Lee

Life 2021, 11(8), 811; https://doi.org/10.3390/life11080811 - 10 Aug 2021

Cited by 28 | Viewed by 5447

Abstract

(1) Background: Nutrition is a key determinant of sarcopenia in later life. (2) Methods: A systematic review of prospective cohort studies examining association of diet quality with muscle mass (MM), muscle strength (MS) or physical performance (PP) among older adults was conducted. A [...] Read more.

(1) Background: Nutrition is a key determinant of sarcopenia in later life. (2) Methods: A systematic review of prospective cohort studies examining association of diet quality with muscle mass (MM), muscle strength (MS) or physical performance (PP) among older adults was conducted. A total of 22,885 results were obtained from a literature search in MEDLINE via PubMed and EMBASE up to November 2020. Inclusion criteria included diet quality assessment via dietary indices or statistical approaches, a sample of adults aged 45 years and over at baseline in a longitudinal study design. (3) Results: Of the 22,885 cohort studies, 14 studies were eligible. Meaningful results were obtained for the Mediterranean diet and Nordic diet regarding the decrease of sarcopenia risk, however results from non-European countries were inconsistent. In addition, due to the insufficient number of studies on Japanese Food Guide Spinning Top (JFG-ST), dietary variety score (DVS), and dietary quality index-international (DQI-I), effectiveness was difficult to prove. Studies using factor analysis to examine dietary patterns suggested that the risk of sarcopenia is increased with a high in saturated fat diet such as westernized pattern etc. (4) Conclusion: In this systematic review it was found that various diet qualities are meaningful to a decreased risk of sarcopenia. Full article

(This article belongs to the Special Issue Sarcopenia and Liver Disease: Current and Future Perspectives)

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15 pages, 3327 KB

Open AccessEditor’s ChoiceArticle

Novel Therapies for Tongue Squamous Cell Carcinoma Patients with High-Grade Tumors

by Yinghua Li, Hao Lin, Lu Chen, Zihao Chen and Weizhong Li

Life 2021, 11(8), 813; https://doi.org/10.3390/life11080813 - 10 Aug 2021

Cited by 9 | Viewed by 3242

Abstract

Background: Tongue squamous cell carcinoma (TSCC) patients with high-grade tumors usually suffer from high occurrence and poor prognosis. The current study aimed at finding the biomarkers related to tumor grades and proposing potential therapies by these biomarkers. Methods: The mRNA expression matrix of [...] Read more.

Background: Tongue squamous cell carcinoma (TSCC) patients with high-grade tumors usually suffer from high occurrence and poor prognosis. The current study aimed at finding the biomarkers related to tumor grades and proposing potential therapies by these biomarkers. Methods: The mRNA expression matrix of TSCC samples from The Cancer Genome Atlas (TCGA) database was analyzed to identify hub proteins related to tumor grades. The mRNA expression patterns of these hub proteins between TSCC and adjacent control samples were validated in three independent TSCC data sets (i.e., GSE9844, GSE30784, and GSE13601). The correlation between cell cycle index and immunotherapy efficacy was tested on the IMvigor210 data set. Based on the structure of hub proteins, virtual screening was applied to compounds to find the potential inhibitors. Results: A total of six cell cycle biomarkers (i.e., BUB1, CCNB2, CDC6, CDC20, CDK1, and MCM2) were selected as hub proteins by protein–protein interaction (PPI) analysis. In the validation data sets, the mRNA expression levels of these hub proteins were higher in tumor samples versus normal controls. The cell cycle index was constructed by the mRNA expression levels of these hub proteins, and patients with a high cell cycle index demonstrated favorable drug response to the immunotherapy. Three small molecules (i.e., ZINC100052685, ZINC8214703, and ZINC85537014) were found to bind with hub proteins and selected as drug candidates. Conclusion: The cell cycle index might provide a novel reference for selecting appropriate cancer patient candidates for immunotherapy. The current research might contribute to the development of precision medicine and improve the prognosis of TSCC. Full article

(This article belongs to the Special Issue Molecular Mechanism and Therapeutic Effect of Drugs in Cancer)

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14 pages, 508 KB

Open AccessEditor’s ChoiceReview

The Impact of SNCA Variations and Its Product Alpha-Synuclein on Non-Motor Features of Parkinson’s Disease

by Luca Magistrelli, Elena Contaldi and Cristoforo Comi

Life 2021, 11(8), 804; https://doi.org/10.3390/life11080804 - 9 Aug 2021

Cited by 38 | Viewed by 9780

Abstract

Parkinson’s disease (PD) is a common and progressive neurodegenerative disease, caused by the loss of dopaminergic neurons in the substantia nigra pars compacta in the midbrain, which is clinically characterized by a constellation of motor and non-motor manifestations. The latter include hyposmia, constipation, [...] Read more.

Parkinson’s disease (PD) is a common and progressive neurodegenerative disease, caused by the loss of dopaminergic neurons in the substantia nigra pars compacta in the midbrain, which is clinically characterized by a constellation of motor and non-motor manifestations. The latter include hyposmia, constipation, depression, pain and, in later stages, cognitive decline and dysautonomia. The main pathological features of PD are neuronal loss and consequent accumulation of Lewy bodies (LB) in the surviving neurons. Alpha-synuclein (α-syn) is the main component of LB, and α-syn aggregation and accumulation perpetuate neuronal degeneration. Mutations in the α-syn gene (SNCA) were the first genetic cause of PD to be identified. Generally, patients carrying SNCA mutations present early-onset parkinsonism with severe and early non-motor symptoms, including cognitive decline. Several SNCA polymorphisms were also identified, and some of them showed association with non-motor manifestations. The functional role of these polymorphisms is only partially understood. In this review we explore the contribution of SNCA and its product, α-syn, in predisposing to the non-motor manifestations of PD. Full article

(This article belongs to the Special Issue Alpha-Synuclein and Non-Motor Symptoms of Parkinson’s Disease)

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13 pages, 2351 KB

Open AccessEditor’s ChoiceArticle

Evidence of Long-Lasting Humoral and Cellular Immunity against SARS-CoV-2 Even in Elderly COVID-19 Convalescents Showing a Mild to Moderate Disease Progression

by Bastian Fischer, Christopher Lindenkamp, Christoph Lichtenberg, Ingvild Birschmann, Cornelius Knabbe and Doris Hendig

Life 2021, 11(8), 805; https://doi.org/10.3390/life11080805 - 9 Aug 2021

Cited by 9 | Viewed by 5151

Abstract

We here evaluate the humoral and cellular immune response against SARS-CoV-2 in 41 COVID-19 convalescents. As previous studies mostly included younger individuals, one advantage of our study is the comparatively high mean age of the convalescents included in the cohort considered (54 ± [...] Read more.

We here evaluate the humoral and cellular immune response against SARS-CoV-2 in 41 COVID-19 convalescents. As previous studies mostly included younger individuals, one advantage of our study is the comparatively high mean age of the convalescents included in the cohort considered (54 ± 8.4 years). While anti-SARS-CoV-2 antibodies were still detectable in 95% of convalescents up to 8 months post infection, an antibody-decay over time was generally observed in most donors. Using a multiplex assay, our data additionally reveal that most convalescents exhibit a broad humoral immunity against different viral epitopes. We demonstrate by flow cytometry that convalescent donors show a significantly elevated number of natural killer cells when compared to healthy controls, while no differences were found concerning other leucocyte subpopulations. We detected a specific long-lasting cellular immune response in convalescents by stimulating immune cells with SARS-CoV-2-specific peptides, covering domains of the viral spike, membrane and nucleocapsid protein, and measuring interferon-γ (IFN-γ) release thereafter. We modified a commercially available ELISA assay for IFN-γ determination in whole-blood specimens of COVID-19 convalescents. One advantage of this assay is that it does not require special equipment and can, thus, be performed in any standard laboratory. In conclusion, our study adds knowledge regarding the persistence of immunity of convalescents suffering from mild to moderate COVID-19. Moreover, our study provides a set of simple methods to characterize and confirm experienced COVID-19. Full article

(This article belongs to the Special Issue Virology Applications to COVID-19 Pandemic)

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10 pages, 1602 KB

Open AccessEditor’s ChoiceArticle

Skeletal Effects of Bone-Targeted TGFbeta Inhibition in a Mouse Model of Duchenne Muscular Dystrophy

by Juliana Marulanda, Iris Boraschi-Diaz, Pierre Beauparlant, Philippe Crine and Frank Rauch

Life 2021, 11(8), 791; https://doi.org/10.3390/life11080791 - 5 Aug 2021

Cited by 1 | Viewed by 3232

Abstract

Duchenne muscular dystrophy (DMD) is a severe progressive muscle disease that is frequently associated with secondary osteoporosis. Previous studies have shown that TGFbeta inactivating antibody improves the muscle phenotype in mdx mice, a model of DMD. In the present study, we assessed the [...] Read more.

Duchenne muscular dystrophy (DMD) is a severe progressive muscle disease that is frequently associated with secondary osteoporosis. Previous studies have shown that TGFbeta inactivating antibody improves the muscle phenotype in mdx mice, a model of DMD. In the present study, we assessed the skeletal effects of treatment with a bone-targeted TGFbeta antibody (PCT-011) in mdx mice. Micro-computed tomography showed that 8 weeks of intraperitoneal administration of PCT-011 (10 mg per kg body mass, 3 times per week) was associated with more than twofold higher trabecular bone volume at the distal femur, which was explained by a higher trabecular number. At the femoral midshaft, PCT-011 exposure increased cortical thickness but did not significantly affect the results of three-point bending tests. Histomorphometric analyses of the lumbar vertebra 4 showed that PCT-011 treatment led to a lower bone formation rate. In conclusion, treatment with the TGFbeta antibody PCT-011 had a positive effect on bone development in mdx mice. Inhibiting TGFbeta activity thus appears to be a promising approach to treat bone fragility in the context of DMD. Full article

(This article belongs to the Special Issue Duchenne Muscular Dystrophy: Mechanisms and Therapeutic Strategies)

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21 pages, 2439 KB

Open AccessEditor’s ChoiceArticle

Shared Molecular Mechanisms of Hypertrophic Cardiomyopathy and Its Clinical Presentations: Automated Molecular Mechanisms Extraction Approach

by Mila Glavaški and Lazar Velicki

Life 2021, 11(8), 785; https://doi.org/10.3390/life11080785 - 3 Aug 2021

Cited by 6 | Viewed by 4015

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease with a prevalence of 1 in 500 people and varying clinical presentations. Although there is much research on HCM, underlying molecular mechanisms are poorly understood, and research on the molecular mechanisms of its [...] Read more.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease with a prevalence of 1 in 500 people and varying clinical presentations. Although there is much research on HCM, underlying molecular mechanisms are poorly understood, and research on the molecular mechanisms of its specific clinical presentations is scarce. Our aim was to explore the molecular mechanisms shared by HCM and its clinical presentations through the automated extraction of molecular mechanisms. Molecular mechanisms were congregated by a query of the INDRA database, which aggregates knowledge from pathway databases and combines it with molecular mechanisms extracted from abstracts and open-access full articles by multiple machine-reading systems. The molecular mechanisms were extracted from 230,072 articles on HCM and 19 HCM clinical presentations, and their intersections were found. Shared molecular mechanisms of HCM and its clinical presentations were represented as networks; the most important elements in the intersections’ networks were found, centrality scores for each element of each network calculated, networks with reduced level of noise generated, and cooperatively working elements detected in each intersection network. The identified shared molecular mechanisms represent possible mechanisms underlying different HCM clinical presentations. Applied methodology produced results consistent with the information in the scientific literature. Full article

(This article belongs to the Special Issue Recent Trends in Computational Research on Diseases)

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17 pages, 1014 KB

Open AccessEditor’s ChoiceReview

Dystonia and Cerebellum: From Bench to Bedside

by Ryoma Morigaki, Ryosuke Miyamoto, Taku Matsuda, Kazuhisa Miyake, Nobuaki Yamamoto and Yasushi Takagi

Life 2021, 11(8), 776; https://doi.org/10.3390/life11080776 - 31 Jul 2021

Cited by 18 | Viewed by 5063

Abstract

Dystonia pathogenesis remains unclear; however, findings from basic and clinical research suggest the importance of the interaction between the basal ganglia and cerebellum. After the discovery of disynaptic pathways between the two, much attention has been paid to the cerebellum. Basic research using [...] Read more.

Dystonia pathogenesis remains unclear; however, findings from basic and clinical research suggest the importance of the interaction between the basal ganglia and cerebellum. After the discovery of disynaptic pathways between the two, much attention has been paid to the cerebellum. Basic research using various dystonia rodent models and clinical studies in dystonia patients continues to provide new pieces of knowledge regarding the role of the cerebellum in dystonia genesis. Herein, we review basic and clinical articles related to dystonia focusing on the cerebellum, and clarify the current understanding of the role of the cerebellum in dystonia pathogenesis. Given the recent evidence providing new hypotheses regarding dystonia pathogenesis, we discuss how the current evidence answers the unsolved clinical questions. Full article

(This article belongs to the Special Issue Dystonia and Related Disorders: From Bench to Bedside)

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20 pages, 3406 KB

Open AccessEditor’s ChoiceArticle

Protective Effects of Probiotics on Cognitive and Motor Functions, Anxiety Level, Visceral Sensitivity, Oxidative Stress and Microbiota in Mice with Antibiotic-Induced Dysbiosis

by Alisa Arslanova, Aksiniya Tarasova, Anastasia Alexandrova, Vera Novoselova, Ilnar Shaidullov, Dilyara Khusnutdinova, Tatiana Grigoryeva, Dina Yarullina, Olga Yakovleva and Guzel Sitdikova

Life 2021, 11(8), 764; https://doi.org/10.3390/life11080764 - 29 Jul 2021

Cited by 20 | Viewed by 4824

Abstract

Accumulating clinical and preclinical data indicate a prominent role of gut microbiota in regulation of physiological functions. The gut-brain axis imbalance due to gut dysbiosis is associated with a range of neurodegenerative diseases. Probiotics were suggested not only to restore intestinal dysbiosis but [...] Read more.

Accumulating clinical and preclinical data indicate a prominent role of gut microbiota in regulation of physiological functions. The gut-brain axis imbalance due to gut dysbiosis is associated with a range of neurodegenerative diseases. Probiotics were suggested not only to restore intestinal dysbiosis but also modulate stress response and improve mood and anxiety symptoms. In this study, we assessed the effects of probiotic lactobacilli on behavioral reactions, the level of oxidative stress and microbiota content in mice administered to broad-spectrum antibiotics. Our study demonstrates that antibiotic treatment of adolescent mice for two weeks resulted in higher mortality and lower weight gain and induced significant changes in behavior including lower locomotor and exploratory activity, reduced muscle strength, visceral hypersensitivity, higher level of anxiety and impaired cognitive functions compared to the control group. These changes were accompanied by decreased diversity and total amount of bacteria, abundance of Proteobacteria and Verrucomicrobia phyla, and reduced Firmicutes/Bacteroides ratio in the gut microbiota. Moreover, a higher level of oxidative stress was found in brain and skeletal muscle tissues of mice treated with antibiotics. Oral administration of two Lactobacillus strains prevented the observed changes and improved not only microbiota content but also the behavioral alterations, suggesting a neuroprotective and antioxidant role of probiotics. Full article

(This article belongs to the Special Issue The Emerging Role of Probiotics in Disease)

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