Life | Editor’s choice Articles

17 pages, 1094 KiB

Open AccessEditor’s ChoiceReview

Potential Reasons for Unresponsiveness to Anti-PD1 Immunotherapy in Young Patients with Advanced Melanoma

by Devayani Machiraju, Sarah Schäfer and Jessica C. Hassel

Life 2021, 11(12), 1318; https://doi.org/10.3390/life11121318 - 30 Nov 2021

Cited by 12 | Viewed by 4874

The impact of age on the clinical benefit of anti-PD1 immunotherapy in advanced melanoma patients has been evolving recently. Due to a reduced immune function in elderly patients, young patients with a robust immune system are theoretically expected to benefit more from the [...] Read more.

The impact of age on the clinical benefit of anti-PD1 immunotherapy in advanced melanoma patients has been evolving recently. Due to a reduced immune function in elderly patients, young patients with a robust immune system are theoretically expected to benefit more from the treatment approach. However, in contrast to this hypothesis, recent studies in patients with metastatic melanoma have demonstrated that immunotherapy, especially with anti-PD1 treatment, is less effective in patients below 65 years, on average, with significantly lower responses and reduced overall survival compared to patients above 65 years of age. Besides, data on young patients are even more sparse. Hence, in this review, we will focus on age-dependent differences in the previously described resistance mechanisms to the treatment and discuss the development of potential combination treatment strategies for enhancing the anti-tumor efficacy of anti-PD1 or PDL1 treatment in young melanoma patients. Full article

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

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16 pages, 2406 KiB

Open AccessEditor’s ChoiceArticle

Properties of GABAergic Neurons Containing Calcium-Permeable Kainate and AMPA-Receptors

by Valery Petrovich Zinchenko, Artem Mikhailovich Kosenkov, Sergei Gennadevich Gaidin, Alexander Igorevich Sergeev, Ludmila Petrovna Dolgacheva and Sultan Tuleukhanovich Tuleukhanov

Life 2021, 11(12), 1309; https://doi.org/10.3390/life11121309 - 27 Nov 2021

Cited by 10 | Viewed by 2975

Abstract

Calcium-permeable kainate and AMPA receptors (CP-KARs and CP-AMPARs), as well as NMDARs, play a pivotal role in plasticity and in regulating neurotransmitter release. Here we visualized in the mature hippocampal neuroglial cultures the neurons expressing CP-AMPARs and CP-KARs. These neurons were visualized by [...] Read more.

Calcium-permeable kainate and AMPA receptors (CP-KARs and CP-AMPARs), as well as NMDARs, play a pivotal role in plasticity and in regulating neurotransmitter release. Here we visualized in the mature hippocampal neuroglial cultures the neurons expressing CP-AMPARs and CP-KARs. These neurons were visualized by a characteristic fast sustained [Ca²⁺]_i increase in response to the agonist of these receptors, domoic acid (DoA), and a selective agonist of GluK1-containing KARs, ATPA. Neurons from both subpopulations are GABAergic. The subpopulation of neurons expressing CP-AMPARs includes a larger percentage of calbindin-positive neurons (39.4 ± 6.0%) than the subpopulation of neurons expressing CP-KARs (14.2 ± 7.5% of CB⁺ neurons). In addition, we have shown for the first time that NH₄Cl-induced depolarization faster induces an [Ca²⁺]_i elevation in GABAergic neurons expressing CP-KARs and CP-AMPARs than in most glutamatergic neurons. CP-AMPARs antagonist, NASPM, increased the amplitude of the DoA-induced Ca²⁺ response in GABAergic neurons expressing CP-KARs, indicating that neurons expressing CP-AMPARs innervate GABAergic neurons expressing CP-KARs. We assume that CP-KARs in inhibitory neurons are involved in the mechanism of outstripping GABA release upon hyperexcitation. Full article

(This article belongs to the Special Issue Glutamate Receptors)

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12 pages, 415 KiB

Open AccessEditor’s ChoiceReview

Colorectal Cancer Screening: Impact of COVID-19 Pandemic and Possible Consequences

by Isabelle Harber, Dania Zeidan and Muhammad N. Aslam

Life 2021, 11(12), 1297; https://doi.org/10.3390/life11121297 - 26 Nov 2021

Cited by 24 | Viewed by 7984

Abstract

Colonoscopy procedure has been the key screening method to detect colorectal cancer (CRC). As a fatal disease, CRC needs early detection. The COVID-19 pandemic caused screening tests (colonoscopy) to be halted and delayed. As a result, there could be dire consequences such as [...] Read more.

Colonoscopy procedure has been the key screening method to detect colorectal cancer (CRC). As a fatal disease, CRC needs early detection. The COVID-19 pandemic caused screening tests (colonoscopy) to be halted and delayed. As a result, there could be dire consequences such as later-stage or missed diagnosis or greater mortality. This report will analyze scientific literature pertaining to interrupted CRC screenings due to COVID-19 while drawing historical parallels from the 1918 flu pandemic. We conducted literature searches in the PubMed database as well as in Google Scholar. One of the main lessons learned from the 1918 flu pandemic was to employ social distancing to stop the spread of the virus. So, the global response at the start and peak of the COVID-19 pandemic was decreased hospital visits for any non-emergency cases. That led to a halt and delays in cancer (including CRC) screenings. The Medical community predicted this lag will cause more CRC cases and deaths in the future. However, reorganizing and changing screening method strategies were helpful during the ongoing pandemic. In conclusion, COVID-19 greatly affected CRC screening, including how we view the future of CRC screening. We can learn from this prospect to better prepare for future pandemics or other public health crises. Full article

(This article belongs to the Special Issue Old and New Pandemics: Challenges for Humans)

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12 pages, 5851 KiB

Open AccessEditor’s ChoiceArticle

Comparing Native Crystal Structures and AlphaFold2 Predicted Water-Soluble G Protein-Coupled Receptor QTY Variants

by Michael A. Skuhersky, Fei Tao, Rui Qing, Eva Smorodina, David Jin and Shuguang Zhang

Life 2021, 11(12), 1285; https://doi.org/10.3390/life11121285 - 24 Nov 2021

Cited by 14 | Viewed by 3590

Abstract

Accurate predictions of 3-dimensional protein structures by AlphaFold2 is a game-changer for biology, especially for structural biology. Here we present the studies of several native chemokine receptors including CCR5, CCR9, CXCR2 and CXCR4 determined by X-ray crystallography, and their water-soluble QTY counter parts [...] Read more.

Accurate predictions of 3-dimensional protein structures by AlphaFold2 is a game-changer for biology, especially for structural biology. Here we present the studies of several native chemokine receptors including CCR5, CCR9, CXCR2 and CXCR4 determined by X-ray crystallography, and their water-soluble QTY counter parts predicted by AlphaFold2. In the native structures, there are hydrophobic amino acids leucine (L), isoleucine (I), valine (V) and phenylalanine (F) in the transmembrane helices. These hydrophobic amino acids are systematically replaced by hydrophilic amino acids glutamine (Q), threonine (T), and tyrosine (Y). Thus, the QTY variants become water-soluble. We also present the superimposed structures of native CCR10, CXCR5, CXCR7 and an olfactory receptor OR1D2 and their water-soluble QTY variants. Since the CryoEM structural determinations for the QTY variants of CCR10^QTY and OR1D2^QTY are in progress, it will be of interest to compare them when the structures become available. The superimposed structures show remarkable similarity within RMSD 1Å–2Å despite significant sequence differences (~26%–~33%). We also show the differences of hydrophobicity patches between the native GPCR and their QTY variants. Our study provides insight into the subtle differences between the hydrophobic helices and hydrophilic helices, and may further stimulate designs of water-soluble membrane proteins and other aggregated proteins. Full article

(This article belongs to the Section Cell Biology and Tissue Engineering)

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19 pages, 2599 KiB

Open AccessEditor’s ChoiceSystematic Review

by Yixi Zhang, Bin La, Baosheng Liang and Yangchun Gu

Life 2021, 11(11), 1277; https://doi.org/10.3390/life11111277 - 22 Nov 2021

Cited by 8 | Viewed by 2990

Abstract

Objective: to evaluate the risk of treatment-related adverse events of different severity and different system with PD-1 or PD-L1 inhibitors. Methods: randomized controlled trials (RCTs) that using PD-1/PD-L1 for cancer treatment were searched in the PubMed, Embase, Cochrane Library, and Web of Science [...] Read more.

Objective: to evaluate the risk of treatment-related adverse events of different severity and different system with PD-1 or PD-L1 inhibitors. Methods: randomized controlled trials (RCTs) that using PD-1/PD-L1 for cancer treatment were searched in the PubMed, Embase, Cochrane Library, and Web of Science from 1 January 2019 to 31 May 2021. Adverse events data were extracted from clinical trials website or original article by two authors separately. Meta-analysis was used to determine risk ratio (RR) and 95% confidence interval (95% CI) of adverse events in PD-1/PD-L1 inhibitors groups compared to that of control groups. Subgroup analyses were also performed. Results: a total of 5,807 studies were initially identified and after exclusion, 41 studies were included in meta-analysis. All the trials were international multicenter, randomized, phase II/III clinical trials, with the median follow-up of 27.5 months on average. Analysis of all grade adverse events showed that PD-1/PD-L1 inhibitors treatment significantly increased the risk of immune-related adverse events, including pruritus (RR: 2.34, 95% CI: 1.85–2.96), rash (RR: 1.53, 95% CI: 1.25–1.87), ALT elevation (RR 1.54, 95% CI 1.23–1.92), AST elevation (AST: RR 1.49, 95% CI 1.20–1.85), hepatitis (RR: 3.54, 95% CI: 1.96–6.38) and hypothyroid (RR: 5.29, 95% CI: 4.00–6.99) compared with that of control group. Besides that, PD-1/PD-L1 inhibitors were associated with higher risk of adverse events related to respiratory system including cough (RR: 1.33, 95% CI: 1.21–1.48), dyspnea (RR:1.23, 95% CI: 1.12–1.35) and chest pain (RR: 1.26, 95% CI: 1.07–1.47) compared with that of control groups in our meta-analysis and the dyspnea was taken high risk both in all grade and grade 3 or higher (RR: 1.55, 95% CI: 1.13–2.12). The risk of arthralgia was increased with PD-1/PD-L1 inhibitors (RR: 1.27, 95% CI: 1.10–1.47). Although the risk of myalgia was similar with PD-1/PD-L1 inhibitors and control groups, under subgroup analysis, PD-1/PD-L1 inhibitors decreased the risk of myalgia (RR: 0.56, 95% CI: 0.45–0.70) compared with that of chemotherapy. Conclusions: our results provide clear evidence that the risk of treatment-related adverse events in PD-1 or PD-L1 varies widely in different system. In particular, when using PD-1/PD-L1 inhibitors for oncology treatment, besides the common immune-related adverse events like pruritus, rash, hepatitis, and hypothyroid, the respiratory disorders and musculoskeletal disorders, such as cough, dyspnea, arthralgia, and myalgia, should also be taken into consideration. Full article

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

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19 pages, 2880 KiB

Open AccessEditor’s ChoiceArticle

COVID-19 and Artificial Intelligence: An Approach to Forecast the Severity of Diagnosis

by Anca Loredana Udriștoiu, Alice Elena Ghenea, Ștefan Udriștoiu, Manuela Neaga, Ovidiu Mircea Zlatian, Corina Maria Vasile, Mihaela Popescu, Eugen Nicolae Țieranu, Alex-Ioan Salan, Adina Andreea Turcu, Dragos Nicolosu, Daniela Calina and Ramona Cioboata

Life 2021, 11(11), 1281; https://doi.org/10.3390/life11111281 - 22 Nov 2021

Cited by 14 | Viewed by 3113

Abstract

(1) Background: The new SARS-COV-2 pandemic overwhelmed intensive care units, clinicians, and radiologists, so the development of methods to forecast the diagnosis’ severity became a necessity and a helpful tool. (2) Methods: In this paper, we proposed an artificial intelligence-based multimodal approach to [...] Read more.

(1) Background: The new SARS-COV-2 pandemic overwhelmed intensive care units, clinicians, and radiologists, so the development of methods to forecast the diagnosis’ severity became a necessity and a helpful tool. (2) Methods: In this paper, we proposed an artificial intelligence-based multimodal approach to forecast the future diagnosis’ severity of patients with laboratory-confirmed cases of SARS-CoV-2 infection. At hospital admission, we collected 46 clinical and biological variables with chest X-ray scans from 475 COVID-19 positively tested patients. An ensemble of machine learning algorithms (AI-Score) was developed to predict the future severity score as mild, moderate, and severe for COVID-19-infected patients. Additionally, a deep learning module (CXR-Score) was developed to automatically classify the chest X-ray images and integrate them into AI-Score. (3) Results: The AI-Score predicted the COVID-19 diagnosis’ severity on the testing/control dataset (95 patients) with an average accuracy of 98.59%, average specificity of 98.97%, and average sensitivity of 97.93%. The CXR-Score module graded the severity of chest X-ray images with an average accuracy of 99.08% on the testing/control dataset (95 chest X-ray images). (4) Conclusions: Our study demonstrated that the deep learning methods based on the integration of clinical and biological data with chest X-ray images accurately predicted the COVID-19 severity score of positive-tested patients. Full article

(This article belongs to the Special Issue Old and New Pandemics: Challenges for Humans)

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13 pages, 4748 KiB

Open AccessEditor’s ChoiceArticle

An Episomal CRISPR/Cas12a System for Mediating Efficient Gene Editing

by Nannan Duan, Shuqing Tang, Baitao Zeng, Zhiqing Hu, Qian Hu, Lingqian Wu, Miaojin Zhou and Desheng Liang

Life 2021, 11(11), 1262; https://doi.org/10.3390/life11111262 - 18 Nov 2021

Cited by 5 | Viewed by 3242

Abstract

(1) Background: Gene editing technology, as represented by CRISPR is a powerful tool used in biomedical science. However, the editing efficiency of such technologies, especially in induced pluripotent stem cells (iPSCs) and other types of stem cells, is low which hinders its application [...] Read more.

(1) Background: Gene editing technology, as represented by CRISPR is a powerful tool used in biomedical science. However, the editing efficiency of such technologies, especially in induced pluripotent stem cells (iPSCs) and other types of stem cells, is low which hinders its application in regenerative medicine; (2) Methods: A gene-editing system, COE, was designed and constructed based on CRISPR/Cas12a and Orip/EBNA1, and its editing efficiency was evaluated in human embryonic kidney 293T (HEK-293T) cells with flow cytometry and restriction fragment length polymorphism (RFLP) analysis. The COE was nucleofected into iPSCs, then, the editing efficiency was verified by a polymerase chain reaction and Sanger sequencing; (3) Results: With the extension of time, COE enables the generation of up to 90% insertion or deletion rates in HEK-293T cells. Furthermore, the deletion of a 2.5 kb fragment containing Exon 51 of the dystrophin gene (DMD) in iPSCs was achieved with high efficiency; out of 14 clones analyzed, 3 were positive. Additionally, the Exon 51-deleted iPSCs derived from cardiomyocytes had similar expression profiles to those of Duchenne muscular dystrophy (DMD) patient-specific iPSCs. Moreover, there was no residue of each component of the plasmid in the editing cells; (4) Conclusions: In this study, a novel, efficient, and safe gene-editing system, COE, was developed, providing a powerful tool for gene editing. Full article

(This article belongs to the Section Genetics and Genomics)

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12 pages, 2996 KiB

Open AccessEditor’s ChoiceArticle

Promoter Demethylation Upregulates STEAP1 Gene Expression in Human Prostate Cancer: In Vitro and In Silico Analysis

by Sandra M. Rocha, Inês Sousa, Inês M. Gomes, Patrícia Arinto, Pedro Costa-Pinheiro, Eduarda Coutinho, Cecília R. Santos, Carmen Jerónimo, Manuel C. Lemos, Luís A. Passarinha, Sílvia Socorro and Cláudio J. Maia

Life 2021, 11(11), 1251; https://doi.org/10.3390/life11111251 - 17 Nov 2021

Cited by 5 | Viewed by 2808

Abstract

The Six Transmembrane Epithelial Antigen of the Prostate (STEAP1) is an oncogene overexpressed in several human tumors, particularly in prostate cancer (PCa). However, the mechanisms involved in its overexpression remain unknown. It is well known that epigenetic modifications may result in [...] Read more.

The Six Transmembrane Epithelial Antigen of the Prostate (STEAP1) is an oncogene overexpressed in several human tumors, particularly in prostate cancer (PCa). However, the mechanisms involved in its overexpression remain unknown. It is well known that epigenetic modifications may result in abnormal gene expression patterns, contributing to tumor initiation and progression. Therefore, this study aimed to analyze the methylation pattern of the STEAP1 gene in PCa versus non-neoplastic cells. Bisulfite amplicon sequencing of the CpG island at the STEAP1 gene promoter showed a higher methylation level in non-neoplastic PNT1A prostate cells than in human PCa samples. Bioinformatic analysis of the GEO datasets also showed the STEAP1 gene promoter as being demethylated in human PCa, and a negative association with STEAP1 mRNA expression was observed. These results are supported by the treatment of non-neoplastic PNT1A cells with DNMT and HDAC inhibitors, which induced a significant increase in STEAP1 mRNA expression. In addition, the involvement of HDAC in the regulation of STEAP1 mRNA expression was corroborated by a negative association between STEAP1 mRNA expression and HDAC4,5,7 and 9 in human PCa. In conclusion, our work indicates that STEAP1 overexpression in PCa can be driven by the hypomethylation of STEAP1 gene promoter. Full article

(This article belongs to the Special Issue Prostate Cancer)

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24 pages, 3783 KiB

Open AccessEditor’s ChoiceArticle

A Label-Free Proteomic and Complementary Metabolomic Analysis of Leaves of the Resurrection Plant Xerophyta schlechteri during Dehydration

by Hawwa Gabier, David L. Tabb, Jill M. Farrant and Mohamed Suhail Rafudeen

Life 2021, 11(11), 1242; https://doi.org/10.3390/life11111242 - 16 Nov 2021

Cited by 2 | Viewed by 2536

Abstract

Vegetative desiccation tolerance, or the ability to survive the loss of ~95% relative water content (RWC), is rare in angiosperms, with these being commonly called resurrection plants. It is a complex multigenic and multi-factorial trait, with its understanding requiring a comprehensive systems biology [...] Read more.

Vegetative desiccation tolerance, or the ability to survive the loss of ~95% relative water content (RWC), is rare in angiosperms, with these being commonly called resurrection plants. It is a complex multigenic and multi-factorial trait, with its understanding requiring a comprehensive systems biology approach. The aim of the current study was to conduct a label-free proteomic analysis of leaves of the resurrection plant Xerophyta schlechteri in response to desiccation. A targeted metabolomics approach was validated and correlated to the proteomics, contributing the missing link in studies on this species. Three physiological stages were identified: an early response to drying, during which the leaf tissues declined from full turgor to a RWC of ~80–70%, a mid-response in which the RWC declined to 40% and a late response where the tissues declined to 10% RWC. We identified 517 distinct proteins that were differentially expressed, of which 253 proteins were upregulated and 264 were downregulated in response to the three drying stages. Metabolomics analyses, which included monitoring the levels of a selection of phytohormones, amino acids, sugars, sugar alcohols, fatty acids and organic acids in response to dehydration, correlated with some of the proteomic differences, giving insight into the biological processes apparently involved in desiccation tolerance in this species. Full article

(This article belongs to the Special Issue Plant Proteomics)

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11 pages, 1577 KiB

Open AccessEditor’s ChoiceReview

The Need for Expanding Pulmonary Rehabilitation Services

by Aroub Lahham and Anne E. Holland

Life 2021, 11(11), 1236; https://doi.org/10.3390/life11111236 - 15 Nov 2021

Cited by 36 | Viewed by 7507

Abstract

Pulmonary rehabilitation is a strongly recommended and effective treatment for people with chronic lung disease. However, access to pulmonary rehabilitation is poor. Globally, pulmonary rehabilitation is accessed by less than 3% of people with chronic lung disease. Barriers to referral, uptake and completion [...] Read more.

Pulmonary rehabilitation is a strongly recommended and effective treatment for people with chronic lung disease. However, access to pulmonary rehabilitation is poor. Globally, pulmonary rehabilitation is accessed by less than 3% of people with chronic lung disease. Barriers to referral, uptake and completion of pulmonary rehabilitation are well documented and linked with organizational, practitioner and patient-related factors. Enhancing the knowledge of health care professionals, family carers, and people with chronic lung disease about the program and its benefits produces modest increases in referral and uptake rates, but evidence of the sustainability of such approaches is limited. Additionally, initiatives focusing on addressing organizational barriers to access, such as expanding services and implementing alternative models to the conventional center-based setting, are not yet widely used in clinical practice. The COVID-19 pandemic has highlighted the urgent need for health care systems to deliver pulmonary rehabilitation programs remotely, safely, and efficiently. This paper will discuss the pressing need to address the issue of the low accessibility of pulmonary rehabilitation. It will also highlight the distinctive challenges to pulmonary rehabilitation delivery in rural and remote regions, as well as low-income countries. Full article

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

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40 pages, 10774 KiB

Open AccessEditor’s ChoiceArticle

Co-Evolution of Opioid and Adrenergic Ligands and Receptors: Shared, Complementary Modules Explain Evolution of Functional Interactions and Suggest Novel Engineering Possibilities

by Robert Root-Bernstein and Beth Churchill

Life 2021, 11(11), 1217; https://doi.org/10.3390/life11111217 - 10 Nov 2021

Cited by 5 | Viewed by 2651

Abstract

Cross-talk between opioid and adrenergic receptors is well-characterized and involves second messenger systems, the formation of receptor heterodimers, and the presence of extracellular allosteric binding regions for the complementary ligand; however, the evolutionary origins of these interactions have not been investigated. We propose [...] Read more.

Cross-talk between opioid and adrenergic receptors is well-characterized and involves second messenger systems, the formation of receptor heterodimers, and the presence of extracellular allosteric binding regions for the complementary ligand; however, the evolutionary origins of these interactions have not been investigated. We propose that opioid and adrenergic ligands and receptors co-evolved from a common set of modular precursors so that they share binding functions. We demonstrate the plausibility of this hypothesis through a review of experimental evidence for molecularly complementary modules and report unexpected homologies between the two receptor types. Briefly, opioids form homodimers also bind adrenergic compounds; opioids bind to conserved extracellular regions of adrenergic receptors while adrenergic compounds bind to conserved extracellular regions of opioid receptors; opioid-like modules appear in both sets of receptors within key ligand-binding regions. Transmembrane regions associated with homodimerization of each class of receptors are also highly conserved across receptor types and implicated in heterodimerization. This conservation of multiple functional modules suggests opioid–adrenergic ligand and receptor co-evolution and provides mechanisms for explaining the evolution of their crosstalk. These modules also suggest the structure of a primordial receptor, providing clues for engineering receptor functions. Full article

(This article belongs to the Section Cell Biology and Tissue Engineering)

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7 pages, 594 KiB

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 17 | Viewed by 3143

Abstract

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 KiB

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 16 | Viewed by 11743

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 KiB

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 4 | Viewed by 2253

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 KiB

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 3076

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 KiB

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 11 | Viewed by 3864

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 KiB

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 12 | Viewed by 3459

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 KiB

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 20 | Viewed by 9437

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 KiB

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 4 | Viewed by 2496

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 KiB

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 23 | Viewed by 3044

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 KiB

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 10 | Viewed by 2954

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 KiB

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 4 | Viewed by 2238

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 KiB

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 3080

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 KiB

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 25 | Viewed by 4450

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 KiB

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 6 | Viewed by 3928

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 KiB

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 10 | Viewed by 3303

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 KiB

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 8 | Viewed by 4189

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 KiB

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 8 | Viewed by 4124

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 KiB

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 26 | Viewed by 3542

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 KiB

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 7 | Viewed by 2925

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 KiB

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 32 | Viewed by 6259

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 KiB

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 15 | Viewed by 11649

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 KiB

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 5 | Viewed by 3940

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 KiB

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 5 | Viewed by 2705

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 KiB

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 2862

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 KiB

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 39 | Viewed by 5343

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 KiB

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 10 | Viewed by 3495

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 KiB

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 3 | Viewed by 2986

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 KiB

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 8 | Viewed by 4001

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 KiB

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 4031

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 KiB

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 18 | Viewed by 4776

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 KiB

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 29 | Viewed by 4249

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 KiB

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 3 | Viewed by 2546

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 KiB

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 11 | Viewed by 4455

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 KiB

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 45 | Viewed by 6920

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 KiB

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 3 | Viewed by 4487

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 KiB

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 2589

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 KiB

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 24 | Viewed by 4407

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 KiB

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 2264

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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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 2628

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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