Life | Editor’s choice

15 pages, 269 KiB

Open AccessEditor’s ChoiceReview

Emerging Pharmacological Treatments for Migraine in the Pediatric Population

by Luigi Francesco Iannone, Francesco De Cesaris and Pierangelo Geppetti

Life 2022, 12(4), 536; https://doi.org/10.3390/life12040536 - 5 Apr 2022

Cited by 6 | Viewed by 3582

Headaches in children and adolescents have high incidence and prevalence rates, with consequent elevated disability costs to individuals and the community. Pediatric migraine is a disorder with substantial clinical differences compared to the adult form. Few clinical trials have been performed specifically on [...] Read more.

Headaches in children and adolescents have high incidence and prevalence rates, with consequent elevated disability costs to individuals and the community. Pediatric migraine is a disorder with substantial clinical differences compared to the adult form. Few clinical trials have been performed specifically on primary headache in pediatric populations using acute and preventative treatments, often with conflicting findings. The limited high-quality data on the effectiveness of treatments are also due to the high placebo effect, in terms of reductions in both the frequency and intensity of migraine attacks in the pediatric population. The recent introduction of calcitonin gene-related peptide (CGRP) pathway inhibitors and ditans is changing the treatment of migraine, but the majority of the data are still limited to adulthood. Thus, few drugs have indications for migraine treatment in the pediatric age group, and limited evidence gives guidance as to the choice of pharmacotherapy. Herein, we review the current evidence of pharmacological treatments and ongoing clinical trials on acute and preventative treatments in the pediatric population with migraine. Full article

(This article belongs to the Special Issue Migraine and Headache in Children and Adolescents)

38 pages, 2969 KiB

Open AccessEditor’s ChoiceReview

Personalized Management and Treatment of Alzheimer’s Disease

by Ramón Cacabelos, Vinogran Naidoo, Olaia Martínez-Iglesias, Lola Corzo, Natalia Cacabelos, Rocío Pego and Juan C. Carril

Life 2022, 12(3), 460; https://doi.org/10.3390/life12030460 - 21 Mar 2022

Cited by 9 | Viewed by 4560

Abstract

Alzheimer’s disease (AD) is a priority health problem with a high cost to society and a large consumption of medical and social resources. The management of AD patients is complex and multidisciplinary. Over 90% of patients suffer from concomitant diseases and require personalized [...] Read more.

Alzheimer’s disease (AD) is a priority health problem with a high cost to society and a large consumption of medical and social resources. The management of AD patients is complex and multidisciplinary. Over 90% of patients suffer from concomitant diseases and require personalized therapeutic regimens to reduce adverse drug reactions (ADRs), drug–drug interactions (DDIs), and unnecessary costs. Men and women show substantial differences in their AD-related phenotypes. Genomic, epigenetic, neuroimaging, and biochemical biomarkers are useful for predictive and differential diagnosis. The most frequent concomitant diseases include hypertension (>25%), obesity (>70%), diabetes mellitus type 2 (>25%), hypercholesterolemia (40%), hypertriglyceridemia (20%), metabolic syndrome (20%), hepatobiliary disorder (15%), endocrine/metabolic disorders (>20%), cardiovascular disorder (40%), cerebrovascular disorder (60–90%), neuropsychiatric disorders (60–90%), and cancer (10%). Over 90% of AD patients require multifactorial treatments with risk of ADRs and DDIs. The implementation of pharmacogenetics in clinical practice can help optimize the limited therapeutic resources available to treat AD and personalize the use of anti-dementia drugs, in combination with other medications, for the treatment of concomitant disorders. Full article

(This article belongs to the Special Issue New Trends in Pharmaceutical Science)

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15 pages, 1168 KiB

Open AccessEditor’s ChoiceArticle

When Nothing Goes Right: Risk Factors and Biomarkers of Right Heart Failure after Left Ventricular Assist Device Implantation

by Thomas Schlöglhofer, Franziska Wittmann, Robert Paus, Julia Riebandt, Anne-Kristin Schaefer, Philipp Angleitner, Marcus Granegger, Philipp Aigner, Dominik Wiedemann, Günther Laufer, Heinrich Schima and Daniel Zimpfer

Life 2022, 12(3), 459; https://doi.org/10.3390/life12030459 - 20 Mar 2022

Cited by 4 | Viewed by 2629

Abstract

Right heart failure (RHF) is a severe complication after left ventricular assist device (LVAD) implantation. The aim of this study was to analyze the incidence, risk factors, and biomarkers for late RHF including the possible superiority of the device and implantation method. This [...] Read more.

Right heart failure (RHF) is a severe complication after left ventricular assist device (LVAD) implantation. The aim of this study was to analyze the incidence, risk factors, and biomarkers for late RHF including the possible superiority of the device and implantation method. This retrospective, single-center study included patients who underwent LVAD implantation between 2014 and 2018. Primary outcome was freedom from RHF over one-year after LVAD implantation; secondary outcomes included pre- and postoperative risk factors and biomarkers for RHF. Of the 145 consecutive patients (HeartMate 3/HVAD: n = 70/75; female: 13.8%), thirty-one patients (21.4%) suffered RHF after a mean LVAD support of median (IQR) 105 (118) days. LVAD implantation method (less invasive: 46.7% vs. 35.1%, p = 0.29) did not differ significantly in patients with or without RHF, whereas the incidence of RHF was lower in HeartMate 3 vs. HVAD patients (12.9% vs. 29.3%, p = 0.016). Multivariate Cox proportional hazard analysis identified HVAD (HR 4.61, 95% CI 1.12–18.98; p = 0.03), early post-op heart rate (HR 0.96, 95% CI 0.93–0.99; p = 0.02), and central venous pressure (CVP) (HR 1.21, 95% CI 1.05–1.39; p = 0.01) as independent risk factors for RHF, but no association of RHF with increased all-cause mortality (HR 1.00, 95% CI 0.99–1.01; p = 0.50) was found. To conclude, HVAD use, lower heart rate, and higher CVP early post-op were independent risk factors for RHF following LVAD implantation. Full article

(This article belongs to the Section Medical Research)

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15 pages, 3081 KiB

Open AccessEditor’s ChoiceArticle

The Possible Role of the Type I Chaperonins in Human Insulin Self-Association

by Federica Pizzo, Maria Rosalia Mangione, Fabio Librizzi, Mauro Manno, Vincenzo Martorana, Rosina Noto and Silvia Vilasi

Life 2022, 12(3), 448; https://doi.org/10.3390/life12030448 - 18 Mar 2022

Cited by 2 | Viewed by 2404

Abstract

Insulin is a hormone that attends to energy metabolism by regulating glucose levels in the bloodstream. It is synthesised within pancreas beta-cells where, before being released into the serum, it is stored in granules as hexamers coordinated by Zn²⁺ and further packaged [...] Read more.

Insulin is a hormone that attends to energy metabolism by regulating glucose levels in the bloodstream. It is synthesised within pancreas beta-cells where, before being released into the serum, it is stored in granules as hexamers coordinated by Zn²⁺ and further packaged in microcrystalline structures. The group I chaperonin cpn60, known for its assembly-assisting function, is present, together with its cochaperonin cpn10, at each step of the insulin secretory pathway. However, the exact function of the heat shock protein in insulin biosynthesis and processing is still far from being understood. Here we explore the possibility that the molecular machine cpn60/cpn10 could have a role in insulin hexameric assembly and its further crystallization. Moreover, we also evaluate their potential protective effect in pathological insulin aggregation. The experiments performed with the cpn60 bacterial homologue, GroEL, in complex with its cochaperonin GroES, by using spectroscopic methods, microscopy and hydrodynamic techniques, reveal that the chaperonins in vitro favour insulin hexameric organisation and inhibit its aberrant aggregation. These results provide new details in the field of insulin assembly and its related disorders. Full article

(This article belongs to the Special Issue How Cosolvents and Cosolutes Affect Biomolecules Stability and Activity)

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14 pages, 1948 KiB

Open AccessEditor’s ChoiceArticle

Single-Cell Image-Based Analysis Reveals Chromatin Changes during the Acquisition of Tamoxifen Drug Resistance

by Han Zhao, Li F. Lin, Joshua Hahn, Junkai Xie, Harvey F. Holman and Chongli Yuan

Life 2022, 12(3), 438; https://doi.org/10.3390/life12030438 - 17 Mar 2022

Cited by 7 | Viewed by 2450

Abstract

Cancer drug resistance is the leading cause of cancer related deaths. The development of drug resistance can be partially contributed to tumor heterogeneity and epigenetic plasticity. However, the detailed molecular mechanism underlying epigenetic modulated drug resistance remains elusive. In this work, we systematically [...] Read more.

Cancer drug resistance is the leading cause of cancer related deaths. The development of drug resistance can be partially contributed to tumor heterogeneity and epigenetic plasticity. However, the detailed molecular mechanism underlying epigenetic modulated drug resistance remains elusive. In this work, we systematically analyzed epigenetic changes in tamoxifen (Tam) responsive and resistant breast cancer cell line MCF7, and adopted a data-driven approach to identify key epigenetic features distinguishing between these two cell types. Significantly, we revealed that DNA methylation and H3K9me3 marks that constitute the heterochromatin are distinctively different between Tam-resistant and -responsive cells. We then performed time-lapse imaging of 5mC and H3K9me3 features using engineered probes. After Tam treatment, we observed a slow transition of MCF7 cells from a drug-responsive to -resistant population based on DNA methylation features. A similar trend was not observed using H3K9me3 probes. Collectively, our results suggest that DNA methylation changes partake in the establishment of Tam-resistant breast cancer cell lines. Instead of global changes in the DNA methylation level, the distribution of DNA methylation features inside the nucleus can be one of the drivers that facilitates the establishment of a drug resistant phenotype in MCF7. Full article

(This article belongs to the Special Issue Epigenetics and Nuclear Architecture)

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13 pages, 1578 KiB

Open AccessEditor’s ChoiceReview

Distinguishing Evolutionary Conservation from Derivedness

by Jason Cheok Kuan Leong, Masahiro Uesaka and Naoki Irie

Life 2022, 12(3), 440; https://doi.org/10.3390/life12030440 - 17 Mar 2022

Cited by 1 | Viewed by 3055

Abstract

While the concept of “evolutionary conservation” has enabled biologists to explain many ancestral features and traits, it has also frequently been misused to evaluate the degree of changes from a common ancestor, or “derivedness”. We propose that the distinction of these two concepts [...] Read more.

While the concept of “evolutionary conservation” has enabled biologists to explain many ancestral features and traits, it has also frequently been misused to evaluate the degree of changes from a common ancestor, or “derivedness”. We propose that the distinction of these two concepts allows us to properly understand phenotypic and organismal evolution. From a methodological aspect, “conservation” mainly considers genes or traits which species have in common, while “derivedness” additionally covers those that are not commonly shared, such as novel or lost traits and genes to evaluate changes from the time of divergence from a common ancestor. Due to these differences, while conservation-oriented methods are effective in identifying ancestral features, they may be prone to underestimating the overall changes accumulated during the evolution of certain lineages. Herein, we describe our recently developed method, “transcriptomic derivedness index”, for estimating the phenotypic derivedness of embryos with a molecular approach using the whole-embryonic transcriptome as a phenotype. Although echinoderms are often considered as highly derived species, our analyses with this method showed that their embryos, at least at the transcriptomic level, may not be much more derived than those of chordates. We anticipate that the future development of derivedness-oriented methods could provide quantitative indicators for finding highly/lowly evolvable traits. Full article

(This article belongs to the Special Issue Selected Papers from The 2nd AsiaEvo Conference)

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17 pages, 8142 KiB

Open AccessEditor’s ChoiceArticle

Alkanes as Membrane Regulators of the Response of Early Membranes to Extreme Temperatures

by Loreto Misuraca, Antonino Caliò, Josephine G. LoRicco, Ingo Hoffmann, Roland Winter, Bruno Demé, Judith Peters and Philippe M. Oger

Life 2022, 12(3), 445; https://doi.org/10.3390/life12030445 - 17 Mar 2022

Cited by 6 | Viewed by 2347

Abstract

One of the first steps in the origin of life was the formation of a membrane, a physical boundary that allowed the retention of molecules in concentrated solutions. The proto-membrane was likely formed by self-assembly of simple readily available amphiphiles, such as short-chain [...] Read more.

One of the first steps in the origin of life was the formation of a membrane, a physical boundary that allowed the retention of molecules in concentrated solutions. The proto-membrane was likely formed by self-assembly of simple readily available amphiphiles, such as short-chain fatty acids and alcohols. In the commonly accepted scenario that life originated near hydrothermal systems, how these very simple membrane bilayers could be stable enough in time remains a debated issue. We used various complementary techniques such as dynamic light scattering, small angle neutron scattering, neutron spin-echo spectroscopy, and Fourier-transform infrared spectroscopy to explore the stability of a novel protomembrane system in which the insertion of alkanes in the midplane is proposed to shift membrane stability to higher temperatures, pH, and hydrostatic pressures. We show that, in absence of alkanes, protomembranes transition into lipid droplets when temperature increases; while in presence of alkanes, membranes persist for longer times in a concentration-dependent manner. Proto-membranes containing alkanes are stable at higher temperatures and for longer times, have a higher bending rigidity, and can revert more easily to their initial state upon temperature variations. Hence, the presence of membrane intercalating alkanes could explain how the first membranes could resist the harsh and changing environment of the hydrothermal systems. Furthermore, modulating the quantity of alkanes in the first membranes appears as a possible strategy to adapt the proto-membrane behavior according to temperature fluctuations, and it offers a first glimpse into the evolution of the first membranes. Full article

(This article belongs to the Special Issue Biomolecular Dynamics Explored by Incoherent Neutron Spectroscopy)

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7 pages, 1297 KiB

Open AccessEditor’s ChoiceCommunication

Why Is the UAG (Amber) Stop Codon Almost Absent in Highly Expressed Bacterial Genes?

by Dominique Belin and Pere Puigbò

Life 2022, 12(3), 431; https://doi.org/10.3390/life12030431 - 16 Mar 2022

Cited by 4 | Viewed by 4493

Abstract

The genome hypothesis postulates that genes in a genome tend to conform to their species’ usage of the codon catalog and the GC content of the DNA. Thus, codon frequencies differ across organisms, including the three termination codons in the standard genetic code. [...] Read more.

The genome hypothesis postulates that genes in a genome tend to conform to their species’ usage of the codon catalog and the GC content of the DNA. Thus, codon frequencies differ across organisms, including the three termination codons in the standard genetic code. Here, we analyze the frequencies of stop codons in a group of highly expressed genes from 196 prokaryotes under strong translational selection. The occurrence of the three translation termination codons is highly biased, with UAA (ochre) being the most prevalent in almost all bacteria. In contrast, UAG (amber) is the least frequent termination codon, e.g., only 321 occurrences (7.4%) in E. coli K-12 substr. W3110. Of the 253 highly expressed genes, only two end with an UAG codon. The strength of the selective bias against UAG in highly expressed genes varies among bacterial genomes, but it is not affected by the GC content of these genomes. In contrast, increased GC content results in a decrease in UAA abundance with a concomitant increase in UGA abundance. We propose that readthrough efficiency and context effects could explain the prevalence of UAA over UAG, particularly in highly expressed genes. Findings from this communication can be utilized for the optimization of gene expression. Full article

(This article belongs to the Section Genetics and Genomics)

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25 pages, 869 KiB

Open AccessEditor’s ChoiceReview

Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude Adaptation

by Katie A. O’Brien, Andrew J. Murray and Tatum S. Simonson

Life 2022, 12(3), 437; https://doi.org/10.3390/life12030437 - 16 Mar 2022

Cited by 13 | Viewed by 7093

Abstract

Hypoxia triggers complex inter- and intracellular signals that regulate tissue oxygen (O₂) homeostasis, adjusting convective O₂ delivery and utilization (i.e., metabolism). Human populations have been exposed to high-altitude hypoxia for thousands of years and, in doing so, have undergone natural [...] Read more.

Hypoxia triggers complex inter- and intracellular signals that regulate tissue oxygen (O₂) homeostasis, adjusting convective O₂ delivery and utilization (i.e., metabolism). Human populations have been exposed to high-altitude hypoxia for thousands of years and, in doing so, have undergone natural selection of multiple gene regions supporting adaptive traits. Some of the strongest selection signals identified in highland populations emanate from hypoxia-inducible factor (HIF) pathway genes. The HIF pathway is a master regulator of the cellular hypoxic response, but it is not the only regulatory pathway under positive selection. For instance, regions linked to the highly conserved Notch signaling pathway are also top targets, and this pathway is likely to play essential roles that confer hypoxia tolerance. Here, we explored the importance of the Notch pathway in mediating the cellular hypoxic response. We assessed transcriptional regulation of the Notch pathway, including close cross-talk with HIF signaling, and its involvement in the mediation of angiogenesis, cellular metabolism, inflammation, and oxidative stress, relating these functions to generational hypoxia adaptation. Full article

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

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13 pages, 2168 KiB

Open AccessEditor’s ChoiceArticle

2-Fluorofucose Attenuates Hydrogen Peroxide-Induced Oxidative Stress in HepG2 Cells via Nrf2/keap1 and NF-κB Signaling Pathways

by Mengjue Tu, Xingshuo Fan, Jianan Shi, Shengnan Jing, Xiaole Xu and Yuqin Wang

Life 2022, 12(3), 406; https://doi.org/10.3390/life12030406 - 11 Mar 2022

Cited by 2 | Viewed by 3055

Abstract

Fucosylation is one of the most important glycan terminal modifications that affects multiple biological activities of proteins. 2-Fluorofucose (2FF), its specific inhibitor, has recently been reported to reveal numerous biological effects by blocking fucosylation both in vitro and in vivo. The current study [...] Read more.

Fucosylation is one of the most important glycan terminal modifications that affects multiple biological activities of proteins. 2-Fluorofucose (2FF), its specific inhibitor, has recently been reported to reveal numerous biological effects by blocking fucosylation both in vitro and in vivo. The current study aimed to evaluate the effect of 2FF on hydrogen peroxide (H₂O₂)-induced oxidative damage in vitro. In our study, treatment with H₂O₂ increased the level of fucosylation, and 2FF improved the cell viability in H₂O₂-treated HepG2 cells. Our study also showed that 2FF significantly decreased the overproduction of reactive oxygen species (ROS) induced by H₂O₂ and the activities of catalase, glutathione and Mn-superoxide dismutase were remarkably increased by 2FF pretreatment. Furthermore, 2FF attenuated H₂O₂-induced early mitochondria dysfunction. The second part of the study revealed that 2FF enhanced antioxidant capacity by affecting Nrf2/keap1 and NF-κB signaling pathways in HepG2 cells. Being pretreated with 2FF significantly increased the nuclear translocation of Nrf2 and simultaneously promoted the expression of downstream proteins, such as HO-1 and NQO1. Moreover, 2FF remarkably suppressed the expression of inflammation-associated proteins. Taken together, these data suggest that 2FF might have a potential therapeutic effect for oxidative stress. Full article

(This article belongs to the Section Pharmaceutical Science)

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9 pages, 505 KiB

Open AccessEditor’s ChoiceArticle

Genetic Workup for Charcot–Marie–Tooth Neuropathy: A Retrospective Single-Site Experience Covering 15 Years

by Chiara Gemelli, Alessandro Geroldi, Sara Massucco, Lucia Trevisan, Ilaria Callegari, Lucio Marinelli, Giulia Ursino, Mehrnaz Hamedani, Giulia Mennella, Silvia Stara, Giovanni Maggi, Laura Mori, Cristina Schenone, Fabio Gotta, Serena Patrone, Alessia Mammi, Paola Origone, Valeria Prada, Lucilla Nobbio, Paola Mandich, Angelo Schenone, Emilia Bellone and Marina Grandis Show full author list Hide full author list

Life 2022, 12(3), 402; https://doi.org/10.3390/life12030402 - 10 Mar 2022

Cited by 8 | Viewed by 3229

Abstract

Charcot–Marie–Tooth (CMT) disease is the most commonly inherited neurological disorder. This study includes patients affected by CMT during regular follow-ups at the CMT clinic in Genova, a neuromuscular university center in the northwest of Italy, with the aim of describing the genetic distribution [...] Read more.

Charcot–Marie–Tooth (CMT) disease is the most commonly inherited neurological disorder. This study includes patients affected by CMT during regular follow-ups at the CMT clinic in Genova, a neuromuscular university center in the northwest of Italy, with the aim of describing the genetic distribution of CMT subtypes in our cohort and reporting a peculiar phenotype. Since 2004, 585 patients (447 index cases) have been evaluated at our center, 64.9% of whom have a demyelinating neuropathy and 35.1% of whom have an axonal neuropathy. A genetic diagnosis was achieved in 66% of all patients, with the following distribution: CMT1A (48%), HNPP (14%), CMT1X (13%), CMT2A (5%), and P0-related neuropathies (7%), accounting all together for 87% of all the molecularly defined neuropathies. Interestingly, we observe a peculiar phenotype with initial exclusive lower limb involvement as well as lower limb involvement that is maintained over time, which we have defined as a “strictly length-dependent” phenotype. Most patients with this clinical presentation shared variants in either HSPB1 or MPZ genes. The identification of distinctive phenotypes such as this one may help to address genetic diagnosis. In conclusion, we describe our diagnostic experiences as a multidisciplinary outpatient clinic, combining a gene-by-gene approach or targeted gene panels based on clinical presentation. Full article

(This article belongs to the Special Issue Rare Neurological Diseases)

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12 pages, 1512 KiB

Open AccessEditor’s ChoiceArticle

Dosimetric Comparison of Ultra-Hypofractionated and Conventionally Fractionated Radiation Therapy Boosts for Patients with High-Risk Prostate Cancer

by Tomasz Piotrowski, Slav Yartsev, Jaroslaw Krawczyk, Marta Adamczyk, Agata Jodda, Julian Malicki and Piotr Milecki

Life 2022, 12(3), 394; https://doi.org/10.3390/life12030394 - 9 Mar 2022

Cited by 1 | Viewed by 2441

Abstract

Recent comparison of an ultra-hypofractionated radiotherapy (UF-RT) boost to a conventionally fractionated (CF-RT) option showed similar toxicity and disease control outcomes. An analysis of the treatment plans for these patients is needed for evaluating calculated doses for different organs, treatment beam-on time, and [...] Read more.

Recent comparison of an ultra-hypofractionated radiotherapy (UF-RT) boost to a conventionally fractionated (CF-RT) option showed similar toxicity and disease control outcomes. An analysis of the treatment plans for these patients is needed for evaluating calculated doses for different organs, treatment beam-on time, and requirements for human and financial resources. Eighty-six plans for UF-RT and 93 plans for CF-RT schemes were evaluated. The biologically equivalent dose, EQD2, summed for the first phase and the boost, was calculated for dose-volume parameters for organs at risk (OARs), as well as for the PTV1. ArcCHECK measurements for the boost plans were used for a comparison of planned and delivered doses. Monitor units and beam-on times were recorded by the Eclipse treatment planning system. Statistical analysis was performed with a significance level of 0.05. Dosimetric parameter values for OARs were well within tolerance for both groups. EQD2 for the PTV1 was on average 84 Gy for UF-RT patients and 76 Gy for CF-RT patients. Gamma passing rate for planned/delivered doses comparison was above 98% for both groups with 3 mm/3% distance to agreement/dose difference criteria. Total monitor units per fraction were 647 ± 94 and 2034 ± 570 for CF-RT and UF-RT, respectively. The total delivery time for boost radiation for the patients in the UF-RT arm was, on average, four times less than the total time for a conventional regimen with statistically equal clinical outcomes for the two arms in this study. Full article

(This article belongs to the Special Issue Cancer Radiotherapy: Recent Advances and Challenges)

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11 pages, 726 KiB

Open AccessEditor’s ChoiceSystematic Review

Contribution of Hypoxic Exercise Testing to Predict High-Altitude Pathology: A Systematic Review

by Thomas Georges, Pierre Menu, Camille Le Blanc, Sophie Ferreol, Marc Dauty and Alban Fouasson-Chailloux

Life 2022, 12(3), 377; https://doi.org/10.3390/life12030377 - 5 Mar 2022

Cited by 6 | Viewed by 3107

Abstract

Altitude travelers are exposed to high-altitude pathologies, which can be potentially serious. Individual susceptibility varies widely and this makes it difficult to predict who will develop these complications. The assessment of physiological adaptations to exercise performed in hypoxia has been proposed to help [...] Read more.

Altitude travelers are exposed to high-altitude pathologies, which can be potentially serious. Individual susceptibility varies widely and this makes it difficult to predict who will develop these complications. The assessment of physiological adaptations to exercise performed in hypoxia has been proposed to help predict altitude sickness. The purpose of this review is to evaluate the contribution of hypoxic exercise testing, achieved in normobaric conditions, in the prediction of severe high-altitude pathology. We performed a systematic review using the databases PubMed, Science Direct and Embase in October 2021 to collect studies reporting physiological adaptations under hypoxic exercise testing and its interest in predicting high-altitude pathology. Eight studies were eligible, concerning 3558 patients with a mean age of 46.9 years old, and a simulated mean altitude reaching of 5092 m. 597 patients presented an acute mountain sickness during their altitude travels. Three different protocols of hypoxic exercise testing were used. Acute mountain sickness was defined using Hackett’s score or the Lake Louise score. Ventilatory and cardiac responses to hypoxia, desaturation in hypoxia, cerebral oxygenation, core temperature, variation in body mass index and some perceived sensations were the highlighted variables associated with acute mountain sickness. A decision algorithm based on hypoxic exercise tests was proposed by one team. Hypoxic exercise testing provides promising information to help predict altitude complications. Its interest should be confirmed by different teams. Full article

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

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14 pages, 1133 KiB

Open AccessEditor’s ChoiceReview

Domesticated LTR-Retrotransposon gag-Related Gene (Gagr) as a Member of the Stress Response Network in Drosophila

by Lidia Nefedova, Alexey Gigin and Alexander Kim

Life 2022, 12(3), 364; https://doi.org/10.3390/life12030364 - 3 Mar 2022

Cited by 2 | Viewed by 2645

Abstract

The most important sources of new components of genomes are transposable elements, which can occupy more than half of the nucleotide sequence of the genome in higher eukaryotes. Among the mobile components of a genome, a special place is occupied by retroelements, which [...] Read more.

The most important sources of new components of genomes are transposable elements, which can occupy more than half of the nucleotide sequence of the genome in higher eukaryotes. Among the mobile components of a genome, a special place is occupied by retroelements, which are similar to retroviruses in terms of their mechanisms of integration into a host genome. The process of positive selection of certain sequences of transposable elements and retroviruses in a host genome is commonly called molecular domestication. There are many examples of evolutionary adaptations of gag (retroviral capsid) sequences as new regulatory sequences of different genes in mammals, where domesticated gag genes take part in placenta functioning and embryogenesis, regulation of apoptosis, hematopoiesis, and metabolism. The only gag-related gene has been found in the Drosophila genome—Gagr. According to the large-scale transcriptomic and proteomic analysis data, the Gagr gene in D. melanogaster is a component of the protein complex involved in the stress response. In this work, we consider the evolutionary processes that led to the formation of a new function of the domesticated gag gene and its adaptation to participation in the stress response. We discuss the possible functional role of the Gagr as part of the complex with its partners in Drosophila, and the pathway of evolution of proteins of the complex in eukaryotes to determine the benefit of the domesticated retroelement gag gene. Full article

(This article belongs to the Special Issue Genomic Impact of Transposable Elements)

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14 pages, 1085 KiB

Open AccessEditor’s ChoiceArticle

CRISPR-Cas Systems in Gut Microbiome of Children with Autism Spectrum Disorders

by Natalia V. Zakharevich, Mikhail S. Nikitin, Alexey S. Kovtun, Vsevolod O. Malov, Olga V. Averina, Valery N. Danilenko and Irena I. Artamonova

Life 2022, 12(3), 367; https://doi.org/10.3390/life12030367 - 3 Mar 2022

Cited by 1 | Viewed by 2452

Abstract

The human gut microbiome is associated with various diseases, including autism spectrum disorders (ASD). Variations of the taxonomical composition in the gut microbiome of children with ASD have been observed repeatedly. However, features and parameters of the microbiome CRISPR-Cas systems in ASD have [...] Read more.

The human gut microbiome is associated with various diseases, including autism spectrum disorders (ASD). Variations of the taxonomical composition in the gut microbiome of children with ASD have been observed repeatedly. However, features and parameters of the microbiome CRISPR-Cas systems in ASD have not been investigated yet. Here, we demonstrate such an analysis in order to describe the overall changes in the microbiome CRISPR-Cas systems during ASD as well as to reveal their potential to be used in diagnostics and therapy. For the systems identification, we used a combination of the publicly available tools suited for completed genomes with subsequent filtrations. In the considered data, the microbiomes of children with ASD contained fewer arrays per Gb of assembly than the control group, but the arrays included more spacers on average. CRISPR arrays from the microbiomes of children with ASD differed from the control group neither in the fractions of spacers with protospacers from known genomes, nor in the sets of known bacteriophages providing protospacers. Almost all bacterial protospacers of the gut microbiome systems for both children with ASD and the healthy ones were located in prophage islands, leaving no room for the systems to participate in the interspecies competition. Full article

(This article belongs to the Special Issue Metagenomics: New Trends and Solutions)

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16 pages, 970 KiB

Open AccessEditor’s ChoiceArticle

Pulmonary Complications after COVID-19

by Petr Jakubec, Kateřina Fišerová, Samuel Genzor and Milan Kolář

Life 2022, 12(3), 357; https://doi.org/10.3390/life12030357 - 28 Feb 2022

Cited by 12 | Viewed by 4959

Abstract

Coronavirus disease 2019 (COVID-19) is a threat to patients not only because of its acute course, but also because of various complications occurring in the following period, that is, more than 28 days after the onset of acute infection. The present study identified [...] Read more.

Coronavirus disease 2019 (COVID-19) is a threat to patients not only because of its acute course, but also because of various complications occurring in the following period, that is, more than 28 days after the onset of acute infection. The present study identified a total of 121 patients hospitalized 29 or more days after the first positive result of a PCR test for SARS-CoV-2, of whom 98 patients were included in the study. Patients were divided into two groups by the time interval between the positive COVID-19 test result and hospitalization date. The time intervals were week 5–11 in an ongoing-COVID group (57.1% of patients) and 12 or more weeks in a post-COVID-group (42.9%). The most frequent reason for hospitalization was respiratory tract infection (58.2%). Pneumonia accounted for 77.2% of these cases. Other reasons for hospitalization were interstitial lung disease (22.4%), pulmonary embolism (8.2%), and sarcoidosis (6.1%). The study group was further divided according to the causes of hospitalization into subgroups with infections and other causes. In the group with infectious diseases, there was a shorter time period between PCR positivity and hospitalization and there were significantly more frequent non-respiratory complications. In the entire sample, the in-hospital mortality was 5.1%. Full article

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

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11 pages, 275 KiB

Open AccessEditor’s ChoiceReview

Alcohol Consumption, ALDH2 Polymorphism as Risk Factors for Upper Aerodigestive Tract Cancer Progression and Prognosis

by Che-Hong Chen, Wen-Lun Wang, Ming-Hung Hsu and Daria Mochly-Rosen

Life 2022, 12(3), 348; https://doi.org/10.3390/life12030348 - 27 Feb 2022

Cited by 12 | Viewed by 4094

Abstract

The upper aerodigestive tract (UADT) is highly susceptible to multiple primary cancers originated from squamous epithelia and constitutes a field of cancerization. Patients with head and neck cancer (head and neck squamous cell carcinoma, HNSCC) are at high risk of developing multiple cancers [...] Read more.

The upper aerodigestive tract (UADT) is highly susceptible to multiple primary cancers originated from squamous epithelia and constitutes a field of cancerization. Patients with head and neck cancer (head and neck squamous cell carcinoma, HNSCC) are at high risk of developing multiple cancers in the esophagus (esophageal squamous cell carcinoma, ESCC). Conversely, esophageal cancer patients are prone to develop multiple primary tumors in the head and neck region. The East Asian-specific dysfunctional ALDH2*2 missense mutation is a genetic risk factor for UADT cancer. It is not only associated with increased incidences of UADT cancer, but is also implicated in faster cancer progression and poorer prognosis. Alcohol use is a major lifestyle risk factor which causes UADT cancer among ALDH2*2 carriers. The accumulation of the immediate metabolite of alcohol, acetaldehyde, is likely the genotoxic agents that is involved in the process of tumorigenesis. This review summarizes recent publications on the risk and association of ALDH2*2 mutation, alcohol consumption in synchronous, metachronous UADT cancer. Possible molecular mechanisms involved in cancer initiation, progress and prognosis are discussed. The review also highlights a need for precision medicine-based preventive and therapeutic strategies by integrating lifestyle and genetic risk factors, such as alcohol consumption, genotypes of the alcohol metabolizing genes, ADH1B and ALDH2, into a risk assessment model for better screening, surveillance and treatment outcome. Full article

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

20 pages, 850 KiB

Open AccessEditor’s ChoiceReview

Staphylococcus epidermidis Controls Opportunistic Pathogens in the Nose, Could It Help to Regulate SARS-CoV-2 (COVID-19) Infection?

by Silvestre Ortega-Peña, Sandra Rodríguez-Martínez, Mario E. Cancino-Diaz and Juan C. Cancino-Diaz

Life 2022, 12(3), 341; https://doi.org/10.3390/life12030341 - 25 Feb 2022

Cited by 8 | Viewed by 6624

Abstract

Staphylococcus epidermidis is more abundant in the anterior nares than internal parts of the nose, but its relative abundance changes along with age; it is more abundant in adolescents than in children and adults. Various studies have shown that S. epidermidis is the [...] Read more.

Staphylococcus epidermidis is more abundant in the anterior nares than internal parts of the nose, but its relative abundance changes along with age; it is more abundant in adolescents than in children and adults. Various studies have shown that S. epidermidis is the guardian of the nasal cavity because it prevents the colonization and infection of respiratory pathogens (bacteria and viruses) through the secretion of antimicrobial molecules and inhibitors of biofilm formation, occupying the space of the membrane mucosa and through the stimulation of the host’s innate and adaptive immunity. There is a strong relationship between the low number of S. epidermidis in the nasal cavity and the increased risk of serious respiratory infections. The direct application of S. epidermidis into the nasal cavity could be an effective therapeutic strategy to prevent respiratory infections and to restore nasal cavity homeostasis. This review shows the mechanisms that S. epidermidis uses to eliminate respiratory pathogens from the nasal cavity, also S. epidermidis is proposed to be used as a probiotic to prevent the development of COVID-19 because S. epidermidis induces the production of interferon type I and III and decreases the expression of the entry receptors of SARS-CoV-2 (ACE2 and TMPRSS2) in the nasal epithelial cells. Full article

(This article belongs to the Special Issue Microbiome of the Respiratory Tract)

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11 pages, 592 KiB

Open AccessEditor’s ChoiceReview

Utility of Keratins as Biomarkers for Human Oral Precancer and Cancer

by Milind Vaidya, Crismita Dmello and Saie Mogre

Life 2022, 12(3), 343; https://doi.org/10.3390/life12030343 - 25 Feb 2022

Cited by 20 | Viewed by 3539

Abstract

Human oral cancer is the single largest group of malignancies in the Indian subcontinent and the sixth largest group of malignancies worldwide. Squamous cell carcinomas (SCC) are the most common epithelial malignancy of the oral cavity, constituting over 90% of oral cancers. About [...] Read more.

Human oral cancer is the single largest group of malignancies in the Indian subcontinent and the sixth largest group of malignancies worldwide. Squamous cell carcinomas (SCC) are the most common epithelial malignancy of the oral cavity, constituting over 90% of oral cancers. About 90% of OSCCs arise from pre-existing, potentially malignant lesions. According to WHO, OSCC has a 5-year survival rate of 45–60%. Late diagnosis, recurrence, and regional or lymph nodal metastases could be the main causes of the high mortality rates. Biomarkers may help categorize and predict premalignant lesions as high risk of developing malignancy, local recurrence, and lymph nodal metastasis. However, at present, there is a dearth of such markers, and this is an area of ongoing research. Keratins (K) or cytokeratins are a group of intermediate filament proteins that show paired and differentiation dependent expression. Our laboratory and others have shown consistent alterations in the expression patterns of keratins in both oral precancerous lesions and tumors. The correlation of these changes with clinicopathological parameters has also been demonstrated. Furthermore, the functional significance of aberrant keratins 8/18 expression in the malignant transformation and progression of oral tumors has also been documented. This article reviews the literature that emphasizes the value of keratins as biomarkers for the prognostication of human oral precancers and cancers. Full article

(This article belongs to the Special Issue Biomarkers, Molecular Mechanism, Microenvironments, and Therapeutics in Oral Cancer)

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12 pages, 3958 KiB

Open AccessEditor’s ChoiceArticle

Ethyl P-Methoxycinnamate: An Active Anti-Metastasis Agent and Chemosensitizer Targeting NFκB from Kaempferia galanga for Melanoma Cells

by Subehan Lallo, Besse Hardianti, Sartini Sartini, Ismail Ismail, Dewi Laela and Yoshihiro Hayakawa

Life 2022, 12(3), 337; https://doi.org/10.3390/life12030337 - 24 Feb 2022

Cited by 5 | Viewed by 3087

Abstract

The most common type of skin cancer is melanoma. While significant advances in chemotherapy have occurred in a few instances, only marginal progress has been made in treating metastatic melanoma. Natural medicine has traditionally been used to treat various illnesses, including cancer. The [...] Read more.

The most common type of skin cancer is melanoma. While significant advances in chemotherapy have occurred in a few instances, only marginal progress has been made in treating metastatic melanoma. Natural medicine has traditionally been used to treat various illnesses, including cancer. The purpose of this study was to identify the active compound in Kaempferia galanga, which could be used to treat melanoma as an anti-metastasis and chemosensitizer agent. The active compound in K. galanga was isolated and identified using chromatography and spectroscopy techniques, and given six compounds. Inhibitory activity on NFκB activation and cell viability was determined using reporter assay methods. Among the isolated compounds, ethyl p-methoxycinnamate (EPMC) demonstrated potent NFκB inhibitory activity against melanoma cell B16F10- NFκB Luc2 with an IC50 of 88.7 μM. Further investigation was conducted by evaluating the anti-metastasis effect of EPMC in vitro by using wound-healing assays, invasion tests, and molecular mechanism assays using Western blotting. NFκB has been implicated in tumorigenesis through the PI3K/Akt/NFκB pathway. The results of this study indicated that EPMCs act as inhibitors of p38 and thereby Akt phosphorylation inhibitors at serine 473, inhibiting NFκB-dependent transcription. Further analysis with paclitaxel demonstrated that the combinations could sensitize to apoptosis in response to well-known chemotherapy agents. Additional studies were conducted using the human melanoma cancer cell line SK-Mel 28. Along with the induction of apoptosis, we observed an increase in p-γH2AX expression (a molecular marker for double strand breaks in DNA damage) in response to treatment with paclitaxel and EPMC. The result showed EPMC to be a potential, viable adjuvant for improving the clinical efficacy of anti-metastatic and cancer chemotherapy. Full article

(This article belongs to the Special Issue Molecular Signaling of Natural Compounds in Oncology)

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19 pages, 3042 KiB

Open AccessEditor’s ChoiceReview

MR Imaging in Real Time Guiding of Therapies in Prostate Cancer

by Yvonne Wimper, Jurgen J. Fütterer and Joyce G. R. Bomers

Life 2022, 12(2), 302; https://doi.org/10.3390/life12020302 - 17 Feb 2022

Cited by 4 | Viewed by 2735

Abstract

Magnetic resonance imaging (MRI)-guided therapy for prostate cancer (PCa) aims to reduce the treatment-associated comorbidity of existing radical treatment, including radical prostatectomy and radiotherapy. Although active surveillance has been used as a conservative method to reduce overtreatment, there is a growing demand for [...] Read more.

Magnetic resonance imaging (MRI)-guided therapy for prostate cancer (PCa) aims to reduce the treatment-associated comorbidity of existing radical treatment, including radical prostatectomy and radiotherapy. Although active surveillance has been used as a conservative method to reduce overtreatment, there is a growing demand for less morbidity and personalized (focal) treatment. The development of multiparametric MRI was of real importance in improving the detection, localization and staging of PCa. Moreover, MRI has been useful for lesion targeting within the prostate, as it is used in the guidance of prostate biopsies, by means of cognitive registration, MRI-ultrasound fusion guidance or direct in-bore MRI-guidance. With regard to PCa therapies, MRI is used for precise probe placement into the lesion and to accurately monitor the treatment in real-time. Moreover, advances in MR-compatible thermal ablation allow for noninvasive real-time temperature mapping during treatment. In this review, we present an overview of the current status of MRI-guided therapies in PCa, focusing on cryoablation, focal laser ablation, high intensity focused ultrasound and transurethral ultrasound ablation. We explain the important role of MRI in the evaluation of the completeness of the ablation and during follow-up. Finally, we will discuss the challenges and future development inherent to these new technologies. Full article

(This article belongs to the Special Issue MRI in Cancer: Ongoing Developments and Controversies)

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12 pages, 1814 KiB

Open AccessEditor’s ChoiceArticle

Comparison of Clinical Efficacy and Safety between 70–150 µm and 100–300 µm Doxorubicin Drug-Eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma

by Jung Woo Yi, Hyun Pyo Hong, Myung Sub Kim, Byung Seok Shin, Heon-Ju Kwon, Byung Ik Kim and Won Sohn

Life 2022, 12(2), 297; https://doi.org/10.3390/life12020297 - 16 Feb 2022

Cited by 8 | Viewed by 3078

Abstract

Background: This study aimed to compare the efficacy and safety of 70–150 μm doxorubicin drug-eluting bead (DEB) transarterial chemoembolization (TACE) with those of 100–300 μm DEB-TACE as first-line treatment in patients with hepatocellular carcinoma (HCC). Methods: We retrospectively investigated 72 patients who underwent [...] Read more.

Background: This study aimed to compare the efficacy and safety of 70–150 μm doxorubicin drug-eluting bead (DEB) transarterial chemoembolization (TACE) with those of 100–300 μm DEB-TACE as first-line treatment in patients with hepatocellular carcinoma (HCC). Methods: We retrospectively investigated 72 patients who underwent TACE with 70–150 μm DEBs (n = 40) or 100–300 μm DEBs (n = 32) for HCC in a tertiary center between March 2013 and May 2019. Initial treatment response and adverse events were assessed using the modified Response Evaluation Criteria in Solid Tumors and the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, respectively. Results: At the 2-month post-treatment assessment, the complete and objective response rates were 47.5% and 85.0%, respectively, for the 70–150 μm group and 34.4% and 81.3%, respectively, for the 100–300 μm group; however, the difference was not statistically significant (p > 0.05). In total, 65% patients in the 70–150 μm group and 59.4 % patients in the 100-300 μm group experienced at least one symptom of post-embolization syndrome after TACE; all symptoms were classified as grade 1 or 2. There was no significant difference between the two groups in terms of post-procedural laboratory changes such as changes in liver enzymes and bilirubin levels (p > 0.05). Laboratory toxicity of grade 3 occurred in three patients, all of which were transient elevation of liver enzyme levels. Hepatobiliary adverse events, such as bile duct injury, biloma, liver abscess, and hepatic infarction, were not observed in either treatment group. Conclusion: This study found no significant difference in tumor response between 70–150 μm and 100–300 μm DEB-TACE. Both groups showed favorable safety profiles, and the difference was not significant. Full article

(This article belongs to the Section Radiobiology and Nuclear Medicine)

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14 pages, 3018 KiB

Open AccessEditor’s ChoiceArticle

Objective Perfusion Assessment in Gracilis Muscle Interposition—A Novel Software-Based Approach to Indocyanine Green Derived Near-Infrared Fluorescence in Reconstructive Surgery

by Leonard A. Lobbes, Richelle J. M. Hoveling, Leonard R. Schmidt, Susanne Berns and Benjamin Weixler

Life 2022, 12(2), 278; https://doi.org/10.3390/life12020278 - 13 Feb 2022

Cited by 5 | Viewed by 2386

Abstract

Background: Gracilis muscle interposition (GMI) is an established treatment option for complex perineal fistulas and reconstruction. The outcome is limited by complications such as necrosis, impaired wound healing and fistula persistence or recurrence. Quantifiable methods of assessing muscle flap perfusion intraoperatively are lacking. [...] Read more.

Background: Gracilis muscle interposition (GMI) is an established treatment option for complex perineal fistulas and reconstruction. The outcome is limited by complications such as necrosis, impaired wound healing and fistula persistence or recurrence. Quantifiable methods of assessing muscle flap perfusion intraoperatively are lacking. This study evaluates a novel and objective software-based assessment of indocyanine green near-infrared fluorescence (ICG-NIRF) in GMI. Methods: Intraoperative ICG-NIRF visualization data of five patients with inflammatory bowel disease (IBD) undergoing GMI for perineal fistula and reconstruction were analyzed retrospectively. A new software was utilized to generate perfusion curves for the specific regions of interest (ROIs) of each GMI by depicting the fluorescence intensity over time. Additionally, a pixel-to-pixel and perfusion zone analysis were performed. The findings were correlated with the clinical outcome. Results: Four patients underwent GMI without postoperative complications within 3 months. The novel perfusion indicators identified here (shape of the perfusion curve, maximum slope value, distribution and range) indicated adequate perfusion. In one patient, GMI failed. In this case, the perfusion indicators suggested impaired perfusion. Conclusions: We present a novel, software-based approach for ICG-NIRF perfusion assessment, identifying previously unknown objective indicators of muscle flap perfusion. Ready for intraoperative real-time use, this method has considerable potential to optimize GMI surgery in the future. Full article

(This article belongs to the Special Issue Recent Advances and Applications of Image-Guided Surgery)

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13 pages, 683 KiB

Open AccessEditor’s ChoiceReview

Telocytes in the Female Reproductive System: Up-to-Date Knowledge, Challenges and Possible Clinical Applications

by Martin Klein, Mária Csöbönyeiová, Ľuboš Danišovič, Lenka Lapides and Ivan Varga

Life 2022, 12(2), 267; https://doi.org/10.3390/life12020267 - 10 Feb 2022

Cited by 14 | Viewed by 6893

Abstract

From their initial description in 2005 to this day, telocytes (TCs) have been described in the ovary, uterine tubes, uterus, vagina, mammary gland, and placenta. Their morphological features, immunophenotype, physiological functions, and roles in disease have been thoroughly documented in both animal models [...] Read more.

From their initial description in 2005 to this day, telocytes (TCs) have been described in the ovary, uterine tubes, uterus, vagina, mammary gland, and placenta. Their morphological features, immunophenotype, physiological functions, and roles in disease have been thoroughly documented in both animal models and human subjects. TCs, with their extremely long cytoplasmic processes called telopodes, play a pivotal role in the morphological and functional interconnection of all the components of the interstitial compartment, but also with constituents of the parenchyma. Although there is no specific immunohistochemical marker for their identification, the most cited are CD 117, CD 34, platelet-derived growth factor receptor (PDGFR), vimentin, and specific markers typical for the female reproductive system (FRS)—estrogen and progesterone receptors (ER and PR). This immunophenotype provides important clues to their physiological roles. Their main functions include the regulation of hormone-dependent processes, intercellular signaling, immune surveillance, microenvironmental maintenance, and the nursing of stem cells. In a situation where TCs are functionally or morphologically decimated, many disease entities may develop, including premature ovarian failure, endometriosis, ectopic pregnancy, infertility, preeclampsia, or even breast cancer. The common denominator of many of these conditions is that their etiopathogenesis is either partially known or completely obscure. Even though the exact role of TCs in these conditions is yet to be revealed, multiple lines of research indicate that their future clinical application may enrich diagnostic-therapeutic strategies of countless conditions. TCs are also heavily debated in terms of their possible use in regenerative medicine and tissue engineering. Some of the concepts related to TC research are strongly substantiated by experimental data, while others are highly speculative. Only future research endeavors will clearly distinguish dead-end lines of research from genuine contributions to the field. Full article

(This article belongs to the Special Issue Structural and Functional Characteristics of Telocytes and Interstitial Cajal cells)

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11 pages, 589 KiB

Open AccessEditor’s ChoiceArticle

Ex-Vivo Preservation with the Organ Care System in High Risk Heart Transplantation

by Sebastian V. Rojas, Murat Avsar, Fabio Ius, David Schibilsky, Tim Kaufeld, Christoph Benk, Ilona Maeding, Michael Berchtold-Herz, Christoph Bara, Friedhelm Beyersdorf, Axel Haverich, Gregor Warnecke and Matthias Siepe

Life 2022, 12(2), 247; https://doi.org/10.3390/life12020247 - 7 Feb 2022

Cited by 17 | Viewed by 3534

Abstract

Objective: Ex vivo organ perfusion is an advanced preservation technique that allows graft assessment and extended ex situ intervals. We hypothesized that its properties might be especially beneficial for high-risk recipients and/or donors with extended criteria. Methods: We reviewed the outcomes of 119 [...] Read more.

Objective: Ex vivo organ perfusion is an advanced preservation technique that allows graft assessment and extended ex situ intervals. We hypothesized that its properties might be especially beneficial for high-risk recipients and/or donors with extended criteria. Methods: We reviewed the outcomes of 119 consecutive heart transplant patients, which were divided into two groups: A (OCS) vs. B (conventional). Ex vivo organ perfusion was performed using the Organ Care System (OCS). Indications for OCS-usage were expected ischemic time of >4 h or >2 h plus given extended donor criteria. Results: Both groups included mostly redo cases (A: 89.7% vs. B: 78.4%; p = 0.121). Incidences of donors with previous cardiac arrest (%) (A: 32.4 vs. B: 22.2; p < 0.05) or LV-hypertrophy (%) (A: 19.1 vs. B: 8.3; p = 0.119) were also increased in Group A. Ex situ time (min) was significantly longer in Group A (A: 381 (74) vs. B: 228 (43); p < 0.05). Ventilation time (days) (A: 10.0 (19.9) vs. B: 24.3 (43.2); p = 0.057), postoperative need for ECLS (%) (A: 25.0 vs. B: 39.2; p = 0.112) and postoperative dialysis (chronic) (%) (A: 4.4 vs. B: 27.5; p < 0.001) were numerically better in the OCS group, without any difference in the occurrence of early graft rejection. The 30-d-survival (A: 92.4% vs. B: 90.2%; p = 0.745) and mid-term survival were statistically not different between both groups. Conclusions: OCS heart allowed safe transplantation of surgically complex recipients with excellent one-year outcomes, despite long preservation times and unfavourable donor characteristics. Furthermore, we observed trends towards decreased ventilation times and fewer ECLS treatments. In times of reduced organ availability and increasing recipient complexity, OCS heart is a valuable instrument that enables otherwise infeasible allocations and contributes to increase surgical safety. Full article

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

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16 pages, 1675 KiB

Open AccessEditor’s ChoiceArticle

Whole Body MRI in the Detection of Lymph Node Metastases in Patients with Testicular Germ Cell Cancer

by Vassiliki Pasoglou, Sandy Van Nieuwenhove, Julien Van Damme, Nicolas Michoux, Aline Van Maanen, Laurence Annet, Jean-Pascal Machiels, Bertrand Tombal and Frederic E. Lecouvet

Life 2022, 12(2), 212; https://doi.org/10.3390/life12020212 - 29 Jan 2022

Cited by 4 | Viewed by 3844

Abstract

Whole-Body Magnetic Resonance Imaging (WB-MRI) is increasingly used for metastatic screening in oncology. This prospective single center study assesses the diagnostic value of WB-MRI including diffusion weighted imaging (DWI) and identifies the sufficient protocol for metastatic lymph node detection in patients with testicular [...] Read more.

Whole-Body Magnetic Resonance Imaging (WB-MRI) is increasingly used for metastatic screening in oncology. This prospective single center study assesses the diagnostic value of WB-MRI including diffusion weighted imaging (DWI) and identifies the sufficient protocol for metastatic lymph node detection in patients with testicular germ cell cancer (TGCC). Forty-three patients underwent contrast enhanced thoraco-abdominopelvic CT (TAP-CT) and WB-MRI with DWI for metastatic lymph node screening. Two independent readers reviewed CTs and WB-MRIs. The diagnostic performance of different imaging protocols (CT, complete WB-MRI, T1W + DWI, T2W + DWI), the agreement between these protocols and the reference standard, the reproducibility of findings and the image quality (Signal and contrast to Noise Ratios, Likert scale) were studied. Reproducibility was very good regardless of both lesion locations (retroperitoneal vs distant lymph nodes, other lesions) and the reader. Diagnostic accuracy of MRI was ≥95% (regardless of the locations and imaging protocol); accuracy of CT was ≥93%. There was a strict overlap of 95% CIs associated with this accuracy between complete WB-MRI, T1W + DWI and T2W + DWI, regardless of the reader. Higher Likert score and SNR were observed for DWI, followed by T2W and T1W sequences. In conclusion, a fast WB-MRI protocol including T2W and DWI is a sufficient, accurate, non-irradiating alternative to TAP-CT for metastatic lymph node screening in TGCC. Full article

(This article belongs to the Special Issue MRI in Cancer: Ongoing Developments and Controversies)

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20 pages, 4558 KiB

Open AccessEditor’s ChoiceArticle

Multi-Planar VMAT Plans for High-Grade Glioma and Glioblastoma Targeting the Hypothalamic-Pituitary Axis Sparing

by Eva Y. W. Cheung, Shirley S. H. Ng, Sapphire H. Y. Yung, Dominic Y. T. Cheng, Fandy Y. C. Chan and Janice K. Y. Cheng

Life 2022, 12(2), 195; https://doi.org/10.3390/life12020195 - 28 Jan 2022

Cited by 4 | Viewed by 3287

Abstract

Background: This study aimed to identify the better arc configuration of volumetric modulated arc therapy (VMAT) for high-grade glioma and glioblastoma, focusing on a dose reduction to the hypothalamic–pituitary axis through an analysis of dose-volumetric parameters, as well as a correlation analysis between [...] Read more.

Background: This study aimed to identify the better arc configuration of volumetric modulated arc therapy (VMAT) for high-grade glioma and glioblastoma, focusing on a dose reduction to the hypothalamic–pituitary axis through an analysis of dose-volumetric parameters, as well as a correlation analysis between the planned target volume (PTV) to organs at risk (OAR) distance and the radiation dose. Method: Twenty-four patients with 9 high-grade glioma and 15 glioblastomas were included in this study. Identical CT, MRI and structure sets of each patient were used for coplanar VMAT (CO-VMAT), dual planar VMAT (DP-VMAT) and multi-planar VMAT (MP-VMAT) planning. The dose constraints adhered to the RTOG0825 and RTOG9006 protocols. The dose-volumetric parameters of each plan were collected for statistical analysis. Correlation analyses were performed between radiation dose and PTV-OARs distance. Results: The DP-VMAT and MP-VMAT achieved a significant dose reduction to most nearby OARs when compared to CO-VMAT, without compromising the dose to PTV, plan homogeneity and conformity. For centrally located OARs, including the hypothalamus, pituitary, brain stem and optic chiasm, the dose reductions ranged from 2.65 Gy to 3.91 Gy (p < 0.001) in DP-VMAT and from 2.57 Gy to 4 Gy (p < 0.001) in MP-VMAT. Similar dose reduction effects were achieved for contralaterally located OARs, including the hippocampus, optic nerve, lens and retina, ranging from 1.06 Gy to 4.37 Gy in DP-VMAT and from 0.54 Gy to 3.39 Gy in MP-VMAT. For ipsilaterally located OARs, DP-VMAT achieved a significant dose reduction of 1.75 Gy to D_max for the optic nerve. In the correlation analysis, DP-VMAT and MP-VMAT showed significant dose reductions to centrally located OARs when the PTV-OAR distance was less than 4 cm. In particular, DP-VMAT offered better sparing to the optic chiasm when it was located less than 2 cm from the PTV than that of MP-VMAT and CO-VMAT. DP-VMAT and MP-VMAT also showed better sparing to the contralateral hippocampus and retina when they were located 3–8 cm from the PTV. Conclusion: The proposed DP-VMAT and MP-VMAT demonstrated significant dose reductions to centrally located and contralateral OARs and maintained the high plan qualities to PTV with good homogeneity and conformity when compared to CO-VMAT for high-grade glioma and glioblastoma. The benefit in choosing DP-VMAT and MP-VMAT over CO-VMAT was substantial when the PTV was located near the hypothalamus, pituitary, optic chiasm, contralateral hippocampus and contralateral retina. Full article

(This article belongs to the Special Issue Cancer Radiotherapy: Recent Advances and Challenges)

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17 pages, 1360 KiB

Open AccessEditor’s ChoiceReview

Abdominal Aortic Aneurysm Formation with a Focus on Vascular Smooth Muscle Cells

by Guoqing Qian, Oluwaseun Adeyanju, Ayobami Olajuyin and Xia Guo

Life 2022, 12(2), 191; https://doi.org/10.3390/life12020191 - 27 Jan 2022

Cited by 33 | Viewed by 10756

Abstract

Abdominal aortic aneurysm (AAA) is a lethal degenerative vascular disease that affects, mostly, the elder population, with a high mortality rate (>80%) upon rupture. It features a dilation of the aortic diameter to larger than 30 mm or more than 50%. Diverse pathological [...] Read more.

Abdominal aortic aneurysm (AAA) is a lethal degenerative vascular disease that affects, mostly, the elder population, with a high mortality rate (>80%) upon rupture. It features a dilation of the aortic diameter to larger than 30 mm or more than 50%. Diverse pathological processes are involved in the development of AAA, including aortic wall inflammation, elastin breakdown, oxidative stress, smooth muscle cell (SMC) phenotypic switching and dysfunction, and extracellular matrix degradation. With open surgery being the only therapeutic option up to date, the lack of pharmaceutical treatment approach calls for identifying novel and effective targets and further understanding the pathological process of AAA. Both lifestyle and genetic predisposition have an important role in increasing the risk of AAA. Several cell types are closely related to the pathogenesis of AAA. Among them, vascular SMCs (VSMCs) are gaining much attention as a critical contributor for AAA initiation and/or progression. In this review, we summarize what is known about AAA, including the risk factors, the pathophysiology, and the established animal models of AAA. In particular, we focus on the VSMC phenotypic switching and dysfunction in AAA formation. Further understanding the regulation of VSMC phenotypic changes may provide novel therapeutic targets for the treatment or prevention of AAA. Full article

(This article belongs to the Special Issue Vascular Smooth Muscle Cell (VSMC) Differentiation)

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14 pages, 2052 KiB

Open AccessEditor’s ChoiceArticle

Fetal Membranes Contribute to Drug Transport across the Feto-Maternal Interface Utilizing the Breast Cancer Resistance Protein (BCRP)

by Ananthkumar Kammala, Meagan Benson, Esha Ganguly, Enkhtuya Radnaa, Talar Kechichian, Lauren Richardson and Ramkumar Menon

Life 2022, 12(2), 166; https://doi.org/10.3390/life12020166 - 23 Jan 2022

Cited by 15 | Viewed by 3478

Abstract

During pregnancy, the placenta is established as a primary organ for drug transport at the maternal-fetal interface. The fetal membranes (FM) also form an interface with maternal tissues; however, their role in drug transport has not been previously investigated. Knowledge of drug transport [...] Read more.

During pregnancy, the placenta is established as a primary organ for drug transport at the maternal-fetal interface. The fetal membranes (FM) also form an interface with maternal tissues; however, their role in drug transport has not been previously investigated. Knowledge of drug transport across this feto-maternal interface along with the placenta can improve new drug development and testing for use during pregnancy. We also hypothesize that extracellular vesicles (exosomes 30–160 nm) released from the FM and placental cells may also contain drug transport proteins and might impact drug trafficking across the feto-maternal interfaces. The objectives were to (1) localize the breast cancer resistance protein (BCRP) in human FM; (2) determine the drug transport function of BCRP in chorion trophoblast cells (CTCs) of the FM; and (3) investigate the presence of BCRP in FM cell-derived exosomes, as a paracrine modifier of the tissue environment for transport functions. The gene and protein expressions of ABCG2/BCRP in FMs were determined by quantitative real-time PCR (qRT-PCR) and western blotting (WB) and were localized by immunohistochemistry (IHC). The surface expression of BCRP in FM cells was determined by flow cytometry. The functional role of BCRP was assessed by an EFFLUX dye multidrug resistance assay. The presence of BCRP in exosomes derived from CTCs and BeWo cells was examined using ExoView^®. Data derived from CTCs are compared with placental trophoblast cells (BeWo). BCRP is expressed and localized in the fetal membrane, primarily in the chorion trophoblast cell layer and scarcely in the amnion epithelial layer (AEC), and primarily localized on both AEC and CTC cell surfaces. Efflux assay data showed that FM cells have similar drug resistance activity as BeWo cells, suggesting that FM also have drug transportation capabilities. BeWo- and CTC-derived exosomes expressed limited BCRP protein on the surface, so it was predominantly contained in the exosomal lumen. As far as we are aware, this is the first study to report BCRP expression in fetal membrane cells and as cargo in fetal membrane-derived exosomes. We report that fetal membrane cells are capable of drug transportation. Based on these results, investigational drug trials should include the FM and its exosomes as possible drug transportation routes in pregnancy. Full article

(This article belongs to the Special Issue New Insights into the Placental and Placental Membrane Pathophysiology of Preterm Birth)

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13 pages, 5273 KiB

Open AccessEditor’s ChoiceArticle

Neutrophils in Extravascular Body Fluids: Cytological-Energy Analysis Enables Rapid, Reliable and Inexpensive Detection of Purulent Inflammation and Tissue Damage

by Petr Kelbich, Petr Vachata, Vilem Maly, Tomas Novotny, Jan Spicka, Inka Matuchova, Tomas Radovnicky, Ivan Stanek, Jan Kubalik, Ondrej Karpjuk, Frantisek Smisko, Eva Hanuljakova and Jan Krejsek

Life 2022, 12(2), 160; https://doi.org/10.3390/life12020160 - 21 Jan 2022

Cited by 4 | Viewed by 4745

Abstract

The simultaneous cytological and metabolic investigation of various extravascular body fluids (EBFs) provides clinically relevant information about the type and intensity of the immune response in particular organ systems. The oxidative burst of professional phagocytes with the concomitant production of reactive oxygen species [...] Read more.

The simultaneous cytological and metabolic investigation of various extravascular body fluids (EBFs) provides clinically relevant information about the type and intensity of the immune response in particular organ systems. The oxidative burst of professional phagocytes with the concomitant production of reactive oxygen species consumes a large amount of oxygen and is the cause of switch to the development of anaerobic metabolism. We assessed the relationships between percentages of neutrophils, aerobic and anaerobic metabolism, and tissue damage via the determination of aspartate aminotransferase catalytic activities (AST) in cerebrospinal fluid (CSF), pleural effusions (PE), abdominal effusions (AE), and synovial fluids (SF). EBFs with 0.0–20.0% neutrophils: 83.0% aerobic and 1.3% strongly anaerobic cases with median of AST = 13.8 IU/L in CSF; 68.0% aerobic and 9.0% strongly anaerobic cases with median of AST = 20.4 IU/L in PE; 77.5% aerobic and 10.5% strongly anaerobic cases with median of AST = 18.0 IU/L in AE; 64.1% aerobic and 7.7% strongly anaerobic cases with median of AST = 13.8 IU/L in SF. EBFs with 80.0–100.0% neutrophils: 4.2% aerobic and 73.7% strongly anaerobic cases with median of AST = 19.2 IU/L in CSF; 7.4% aerobic and 77.3% strongly anaerobic cases with median of AST = 145.2 IU/L in PE; 11.8% aerobic and 73.7% strongly anaerobic cases with median of AST = 61.8 IU/L in AE; 25.5% aerobic and 38.2% strongly anaerobic cases with median of AST = 37.2 IU/L in SF. The significant presence of neutrophils, concomitant strong anaerobic metabolism, and elevated AST in various EBFs are reliable signs of damaging purulent inflammation. Full article

(This article belongs to the Special Issue Current Research in Inflammatory Response to Injury and Diseases)

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15 pages, 35950 KiB

Open AccessEditor’s ChoiceArticle

A Novel Anti-B7-H3 × Anti-CD3 Bispecific Antibody with Potent Antitumor Activity

by Yan Feng, Kun Xie, Yanxin Yin, Bingyu Li, Chenyu Pi, Xiaoqing Xu, Tao Huang, Jingming Zhang, Bo Wang, Hua Gu and Jianmin Fang

Life 2022, 12(2), 157; https://doi.org/10.3390/life12020157 - 21 Jan 2022

Cited by 10 | Viewed by 5168

Abstract

B7-H3 plays an important role in tumor apoptosis, proliferation, adhesion, angiogenesis, invasion, migration, and evasion of immune surveillance. It is overexpressed in various human solid tumor tissues. In patients, B7-H3 overexpression correlates with advanced stages, poor clinical outcomes, and resistance to therapy. The [...] Read more.

B7-H3 plays an important role in tumor apoptosis, proliferation, adhesion, angiogenesis, invasion, migration, and evasion of immune surveillance. It is overexpressed in various human solid tumor tissues. In patients, B7-H3 overexpression correlates with advanced stages, poor clinical outcomes, and resistance to therapy. The roles of B7-H3 in tumor progression make it a potential candidate for targeted therapy. Here, we generated a mouse anti-human B7-H3 antibody and demonstrated its binding activity via Tongji University Suzhou Instituteprotein-based and cell-based assays. We then developed a novel format anti-B7-H3 × anti-CD3 bispecific antibody based on the antibody-binding fragment of the anti-B7-H3 antibody and single-chain variable fragment structure of anti-CD3 antibody (OKT3) and demonstrated that this bispecific antibody mediated potent cytotoxic activities against various B7-H3-positive tumor cell lines in vitro by improving T cell activation and proliferation. This bispecific antibody also demonstrated potent antitumor activity in humanized mice xenograft models. These results revealed that the novel anti-B7-H3 × anti-CD3 bispecific antibody has the potential to be employed in treatment of B7-H3-positive solid tumors. Full article

(This article belongs to the Special Issue Bispecific Antibodies: Design, Isolation, Perspectives of Use)

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13 pages, 566 KiB

Open AccessEditor’s ChoiceReview

The Mediating Role of the Gut Microbiota in the Physical Growth of Children

by Magdalena Durda-Masny, Joanna Ciomborowska-Basheer, Izabela Makałowska and Anita Szwed

Life 2022, 12(2), 152; https://doi.org/10.3390/life12020152 - 20 Jan 2022

Cited by 13 | Viewed by 5014

Abstract

Gut microbiota succession overlaps with intensive growth in infancy and early childhood. The multitude of functions performed by intestinal microbes, including participation in metabolic, hormonal, and immune pathways, makes the gut bacterial community an important player in cross-talk between intestinal processes and growth. [...] Read more.

Gut microbiota succession overlaps with intensive growth in infancy and early childhood. The multitude of functions performed by intestinal microbes, including participation in metabolic, hormonal, and immune pathways, makes the gut bacterial community an important player in cross-talk between intestinal processes and growth. Long-term disturbances in the colonization pattern may affect the growth trajectory, resulting in stunting or wasting. In this review, we summarize the evidence on the mediating role of gut microbiota in the mechanisms controlling the growth of children. Full article

(This article belongs to the Section Microbiology)

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51 pages, 1098 KiB

Open AccessEditor’s ChoiceArticle

Pediatric Headache in Primary Care and Emergency Departments: Consensus with RAND/UCLA Method

by Giovanni Prezioso, Agnese Suppiej, Valentina Alberghini, Patrizia Bergonzini, Maria Elena Capra, Ilaria Corsini, Alessandro De Fanti, Elisa Fiumana, Martina Fornaro, Lucia Marangio, Paolo Ricciardelli, Laura Serra, Duccio Maria Cordelli, Susanna Esposito and the Emilia-Romagna Headache Study Group

Life 2022, 12(2), 142; https://doi.org/10.3390/life12020142 - 19 Jan 2022

Cited by 9 | Viewed by 6371

Abstract

Headache is the most frequent neurological symptom in childhood and the main reason for admission to pediatric emergency departments. The aim of this consensus document is to define a shared clinical pathway between primary care pediatricians (PCP) and hospitals for the management of [...] Read more.

Headache is the most frequent neurological symptom in childhood and the main reason for admission to pediatric emergency departments. The aim of this consensus document is to define a shared clinical pathway between primary care pediatricians (PCP) and hospitals for the management of children presenting with headache. For the purposes of the study, a group of hospital pediatricians and a group of PCP from the Emilia Romagna’s health districts were selected to achieve consensus using the RAND/UCLA appropriateness method. Thirty-nine clinical scenarios were developed: for each scenario, participants were asked to rank the appropriateness of each option from 1 to 9. Agreement was reached if ≥75% of participants ranked within the same range of appropriateness. The answers, results, and discussion helped to define the appropriateness of procedures with a low level of evidence regarding different steps of the diagnostic-therapeutic process: primary care evaluation, emergency department evaluation, hospital admission, acute therapy, prophylaxis, and follow-up. The RAND proved to be a valid method to value appropriateness of procedures and define a diagnostic-therapeutic pathway suitable to the local reality in the management of pediatric headache. From our results, some useful recommendations were developed for optimizing the healthcare professionals’ network among primary care services and hospitals. Full article

(This article belongs to the Special Issue Migraine and Headache in Children and Adolescents)

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25 pages, 19211 KiB

Open AccessEditor’s ChoiceArticle

Ritonavir and xk263 Binding-Unbinding with HIV-1 Protease: Pathways, Energy and Comparison

by Jianan Sun, Mark Anthony V. Raymundo and Chia-En A. Chang

Life 2022, 12(1), 116; https://doi.org/10.3390/life12010116 - 13 Jan 2022

Cited by 4 | Viewed by 2233

Abstract

Understanding non-covalent biomolecular recognition, which includes drug–protein bound states and their binding/unbinding processes, is of fundamental importance in chemistry, biology, and medicine. Fully revealing the factors that govern the binding/unbinding processes can further assist in designing drugs with desired binding kinetics. HIV protease [...] Read more.

Understanding non-covalent biomolecular recognition, which includes drug–protein bound states and their binding/unbinding processes, is of fundamental importance in chemistry, biology, and medicine. Fully revealing the factors that govern the binding/unbinding processes can further assist in designing drugs with desired binding kinetics. HIV protease (HIVp) plays an integral role in the HIV life cycle, so it is a prime target for drug therapy. HIVp has flexible flaps, and the binding pocket can be accessible by a ligand via various pathways. Comparing ligand association and dissociation pathways can help elucidate the ligand–protein interactions such as key residues directly involved in the interaction or specific protein conformations that determine the binding of a ligand under certain pathway(s). Here, we investigated the ligand unbinding process for a slow binder, ritonavir, and a fast binder, xk263, by using unbiased all-atom accelerated molecular dynamics (aMD) simulation with a re-seeding approach and an explicit solvent model. Using ritonavir-HIVp and xk263-HIVp ligand–protein systems as cases, we sampled multiple unbinding pathways for each ligand and observed that the two ligands preferred the same unbinding route. However, ritonavir required a greater HIVp motion to dissociate as compared with xk263, which can leave the binding pocket with little conformational change of HIVp. We also observed that ritonavir unbinding pathways involved residues which are associated with drug resistance and are distal from catalytic site. Analyzing HIVp conformations sampled during both ligand–protein binding and unbinding processes revealed significantly more overlapping HIVp conformations for ritonavir-HIVp rather than xk263-HIVp. However, many HIVp conformations are unique in xk263-HIVp unbinding processes. The findings are consistent with previous findings that xk263 prefers an induced-fit model for binding and unbinding, whereas ritonavir favors a conformation selection model. This study deepens our understanding of the dynamic process of ligand unbinding and provides insights into ligand–protein recognition mechanisms and drug discovery. Full article

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

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15 pages, 700 KiB

Open AccessEditor’s ChoiceReview

FGFR Pathway Inhibition in Gastric Cancer: The Golden Era of an Old Target?

by Csongor G. Lengyel, Sadaqat Hussain, Andreas Seeber, Sara Jamil Nidhamalddin, Dario Trapani, Baker S. Habeeb, Essam Elfaham, Syed Ayub Mazher, Fahmi Seid, Shah Z. Khan, Khalid El Bairi, Andrew Odhiambo, Sara C. Altuna and Angelica Petrillo

Life 2022, 12(1), 81; https://doi.org/10.3390/life12010081 - 7 Jan 2022

Cited by 19 | Viewed by 5950

Abstract

Gastric cancer (GC) is the third leading cause of cancer-associated death worldwide. The majority of patients are diagnosed at an advanced/metastatic stage of disease due to a lack of specific symptoms and lack of screening programs, especially in Western countries. Thus, despite the [...] Read more.

Gastric cancer (GC) is the third leading cause of cancer-associated death worldwide. The majority of patients are diagnosed at an advanced/metastatic stage of disease due to a lack of specific symptoms and lack of screening programs, especially in Western countries. Thus, despite the improvement in GC therapeutic opportunities, the survival is disappointing, and the definition of the optimal treatment is still an unmet need. Novel diagnostic techniques were developed in clinical trials in order to characterize the genetic profile of GCs and new potential molecular pathways, such as the Fibroblast Growth Factor Receptor (FGFR) pathway, were identified in order to improve patient’s survival by using target therapies. The aim of this review is to summarize the role and the impact of FGFR signaling in GC and to provide an overview regarding the potential effectiveness of anti-FGFR agents in GC treatment in the context of precision medicine. Full article

(This article belongs to the Special Issue Current and Novel Therapeutic Strategies for Cancers in the Era of Personalized Treatment)

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12 pages, 5917 KiB

Open AccessEditor’s ChoiceArticle

Surveillance of Pathogenicity of Rhizoctonia solani Japanese Isolates with Varied Anastomosis Groups and Subgroups on Arabidopsis thaliana

by Mai Mohsen Ahmed Abdelghany, Maria Kurikawa, Megumi Watanabe, Hidenori Matsui, Mikihiro Yamamoto, Yuki Ichinose, Kazuhiro Toyoda, Yusuke Kouzai and Yoshiteru Noutoshi

Life 2022, 12(1), 76; https://doi.org/10.3390/life12010076 - 6 Jan 2022

Cited by 5 | Viewed by 3146

Abstract

Rhizoctonia solani is a necrotrophic plant pathogen with a wide host range. R. solani is a species complex consisting of thirteen anastomosis groups (AGs) defined by compatibility of hyphal fusion reaction and subgroups based on cultural morphology. The relationship between such classifications and [...] Read more.

Rhizoctonia solani is a necrotrophic plant pathogen with a wide host range. R. solani is a species complex consisting of thirteen anastomosis groups (AGs) defined by compatibility of hyphal fusion reaction and subgroups based on cultural morphology. The relationship between such classifications and host specificity remains elusive. Here, we investigated the pathogenicity of seventeen R. solani isolates (AG-1 to 7) in Japan towards Arabidopsis thaliana using leaf and soil inoculations. The tested AGs, except AG-3 and AG-6, induced symptoms in both methods with variations in pathogenicity. The virulence levels differed even within the same AG and subgroup. Some isolates showed tissue-specific infection behavior. Thus, the AGs and their subgroups are suggested to be not enough to define the virulence (host and tissue specificity) of R. solani. We also evaluated the virulence of the isolates on Arabidopsis plants pretreated with salicylic acid, jasmonic acid, and ethylene. No obvious effects were detected on the symptom formation by the virulence isolates, but ethylene and salicylic acid slightly enhanced the susceptibility to the weak and nonvirulent isolates. R. solani seems to be able to overcome the induced defense by these phytohormones in the infection to Arabidopsis. Full article

(This article belongs to the Collection State of the Art in Plant Science)

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16 pages, 1104 KiB

Open AccessEditor’s ChoiceArticle

COVID-19—A Trigger Factor for Severe Immune-Mediated Thrombocytopenia in Active Rheumatoid Arthritis

by Anca Bobircă, Florin Bobircă, Ioan Ancuța, Anca Florescu, Mihai Bojincă, Alice Muscă, Dan Nicolae Florescu, Lucian Mihai Florescu, Romina Marina Sima, Alesandra Florescu and Anca Emanuela Mușetescu

Life 2022, 12(1), 77; https://doi.org/10.3390/life12010077 - 6 Jan 2022

Cited by 7 | Viewed by 7166

Abstract

Thrombocytopenia is defined as a platelet count below 150,000/mm³ for adults. There is still controversy about whether individuals with platelet counts of 100,000/mm³ to 150,000/mm³ should be classified as having genuine thrombocytopenia or borderline thrombocytopenia. Thrombocytopenia is considered mild when [...] Read more.

Thrombocytopenia is defined as a platelet count below 150,000/mm³ for adults. There is still controversy about whether individuals with platelet counts of 100,000/mm³ to 150,000/mm³ should be classified as having genuine thrombocytopenia or borderline thrombocytopenia. Thrombocytopenia is considered mild when the platelet count is between 70,000 and 150,000/mm³ and severe if the count is less than 20,000/mm³. Thrombocytopenia in rheumatoid arthritis is a rare complication, with an incidence estimated between 3 and 10%. The main etiological aspects include drug-induced thrombocytopenia and immune thrombocytopenic purpura. The most common hematological abnormalities in SARS-CoV-2 infection are lymphopenia and thrombocytopenia. It has been observed that the severity of thrombocytopenia correlates with the severity of the infection, being a poor prognosis indicator and a risk factor for mortality. COVID-19 can stimulate the immune system to destroy platelets by increasing the production of autoantibodies and immune complexes. Autoimmunity induced by viral infections can be related to molecular mimicry, cryptic antigen expression and also spreading of the epitope. During the COVID-19 pandemic, it is of great importance to include the SARS-CoV-2 infection in differential diagnoses, due to the increased variability in forms of presentation of this pathology. In this review, our aim is to present one of the most recently discovered causes of thrombocytopenia, which is the SARS-CoV-2 infection and the therapeutic challenges it poses in association with an autoimmune disease such as rheumatoid arthritis. Full article

(This article belongs to the Special Issue Frontiers in Vascular Biology)

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11 pages, 893 KiB

Open AccessEditor’s ChoiceArticle

Effects of Pre-Term Birth on the Cardio-Respiratory Responses to Hypoxic Exercise in Children

by Benjamin J. Narang, Giorgio Manferdelli, Katja Kepic, Alexandros Sotiridis, Damjan Osredkar, Nicolas Bourdillon, Grégoire P. Millet and Tadej Debevec

Life 2022, 12(1), 79; https://doi.org/10.3390/life12010079 - 6 Jan 2022

Cited by 6 | Viewed by 4311

Abstract

Pre-term birth is associated with numerous cardio-respiratory sequelae in children. Whether these impairments impact the responses to exercise in normoxia or hypoxia remains to be established. Fourteen prematurely-born (PREM) (Mean ± SD; gestational age 29 ± 2 weeks; age 9.5 ± 0.3 years), [...] Read more.

Pre-term birth is associated with numerous cardio-respiratory sequelae in children. Whether these impairments impact the responses to exercise in normoxia or hypoxia remains to be established. Fourteen prematurely-born (PREM) (Mean ± SD; gestational age 29 ± 2 weeks; age 9.5 ± 0.3 years), and 15 full-term children (CONT) (gestational age 39 ± 1 weeks; age 9.7 ± 0.9 years), underwent incremental exercise tests to exhaustion in normoxia (FiO₂ = 20.9%) and normobaric hypoxia (FiO₂ = 13.2%) on a cycle ergometer. Cardio-respiratory variables were measured throughout. Peak power output was higher in normoxia than hypoxia (103 ± 17 vs. 77 ± 18 W; p < 0.001), with no difference between CONT and PREM (94 ± 23 vs. 86 ± 19 W; p = 0.154). VO₂peak was higher in normoxia than hypoxia in CONT (50.8 ± 7.2 vs. 43.8 ± 9.9 mL·kg⁻¹·min⁻¹; p < 0.001) but not in PREM (48.1 ± 7.5 vs. 45.0 ± 6.8 mL·kg⁻¹·min⁻¹; p = 0.137; interaction p = 0.044). Higher peak heart rate (187 ± 11 vs. 180 ± 10 bpm; p = 0.005) and lower stroke volume (72 ± 13 vs. 77 ± 14 mL; p = 0.004) were observed in normoxia versus hypoxia in CONT, with no such differences in PREM (p = 0.218 and >0.999, respectively). In conclusion, premature birth does not appear to exacerbate the negative effect of hypoxia on exercise capacity in children. Further research is warranted to identify whether prematurity elicits a protective effect, and to clarify the potential underlying mechanisms. Full article

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

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13 pages, 7424 KiB

Open AccessEditor’s ChoiceArticle

Ginsenoside F1 Protects the Brain against Amyloid Beta-Induced Toxicity by Regulating IDE and NEP

by Yee-Jin Yun, Bong-Hwan Park, Jingang Hou, Jung-Pyo Oh, Jin-Hee Han and Sun-Chang Kim

Life 2022, 12(1), 58; https://doi.org/10.3390/life12010058 - 1 Jan 2022

Cited by 15 | Viewed by 3475

Abstract

Ginsenoside F1, the metabolite of Rg1, is one of the most important constituents of Panax ginseng. Although the effects of ginsenosides on amyloid beta (Aβ) aggregation in the brain are known, the role of ginsenoside F1 remains unclear. Here, we investigated the [...] Read more.

Ginsenoside F1, the metabolite of Rg1, is one of the most important constituents of Panax ginseng. Although the effects of ginsenosides on amyloid beta (Aβ) aggregation in the brain are known, the role of ginsenoside F1 remains unclear. Here, we investigated the protective effect of ginsenoside F1 against Aβ aggregation in vivo and in vitro. Treatment with 2.5 μM ginsenoside F1 reduced Aβ-induced cytotoxicity by decreasing Aβ aggregation in mouse neuroblastoma neuro-2a (N2a) and human neuroblastoma SH-SY5Y neuronal cell lines. Western blotting, real-time PCR, and siRNA analysis revealed an increased level of insulin-degrading enzyme (IDE) and neprilysin (NEP). Furthermore, liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis confirmed that ginsenoside F1 could pass the blood–brain barrier within 2 h after administration. Immunostaining results indicate that ginsenoside F1 reduces Aβ plaques in the hippocampus of APPswe/PSEN1dE9 (APP/PS1) double-transgenic Alzheimer’s disease (AD) mice. Consistently, increased levels of IDE and NEP protein and mRNA were observed after the 8-week administration of 10 mg/kg/d ginsenoside F1. These data indicate that ginsenoside F1 is a promising therapeutic candidate for AD. Full article

(This article belongs to the Section Pharmaceutical Science)

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22 pages, 1918 KiB

Open AccessEditor’s ChoiceReview

Third-Generation Sequencing: The Spearhead towards the Radical Transformation of Modern Genomics

by Konstantina Athanasopoulou, Michaela A. Boti, Panagiotis G. Adamopoulos, Paraskevi C. Skourou and Andreas Scorilas

Life 2022, 12(1), 30; https://doi.org/10.3390/life12010030 - 26 Dec 2021

Cited by 119 | Viewed by 24153

Abstract

Although next-generation sequencing (NGS) technology revolutionized sequencing, offering a tremendous sequencing capacity with groundbreaking depth and accuracy, it continues to demonstrate serious limitations. In the early 2010s, the introduction of a novel set of sequencing methodologies, presented by two platforms, Pacific Biosciences (PacBio) [...] Read more.

Although next-generation sequencing (NGS) technology revolutionized sequencing, offering a tremendous sequencing capacity with groundbreaking depth and accuracy, it continues to demonstrate serious limitations. In the early 2010s, the introduction of a novel set of sequencing methodologies, presented by two platforms, Pacific Biosciences (PacBio) and Oxford Nanopore Sequencing (ONT), gave birth to third-generation sequencing (TGS). The innovative long-read technologies turn genome sequencing into an ease-of-handle procedure by greatly reducing the average time of library construction workflows and simplifying the process of de novo genome assembly due to the generation of long reads. Long sequencing reads produced by both TGS methodologies have already facilitated the decipherment of transcriptional profiling since they enable the identification of full-length transcripts without the need for assembly or the use of sophisticated bioinformatics tools. Long-read technologies have also provided new insights into the field of epitranscriptomics, by allowing the direct detection of RNA modifications on native RNA molecules. This review highlights the advantageous features of the newly introduced TGS technologies, discusses their limitations and provides an in-depth comparison regarding their scientific background and available protocols as well as their potential utility in research and clinical applications. Full article

(This article belongs to the Special Issue Third-Generation Sequencing: Recent Advances and Applications in the Era of Genomics, Transcriptomics and Epitranscriptomics)

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17 pages, 2648 KiB

Open AccessEditor’s ChoiceArticle

An Interplay between Viruses and Bacteria Associated with the White Sea Sponges Revealed by Metagenomics

by Anastasiia Rusanova, Victor Fedorchuk, Stepan Toshchakov, Svetlana Dubiley and Dmitry Sutormin

Life 2022, 12(1), 25; https://doi.org/10.3390/life12010025 - 24 Dec 2021

Cited by 5 | Viewed by 4140

Abstract

Sponges are remarkable holobionts harboring extremely diverse microbial and viral communities. However, the interactions between the components within holobionts and between a holobiont and environment are largely unknown, especially for polar organisms. To investigate possible interactions within and between sponge-associated communities, we probed [...] Read more.

Sponges are remarkable holobionts harboring extremely diverse microbial and viral communities. However, the interactions between the components within holobionts and between a holobiont and environment are largely unknown, especially for polar organisms. To investigate possible interactions within and between sponge-associated communities, we probed the microbiomes and viromes of cold-water sympatric sponges Isodictya palmata (n = 2), Halichondria panicea (n = 3), and Halichondria sitiens (n = 3) by 16S and shotgun metagenomics. We showed that the bacterial and viral communities associated with these White Sea sponges are species-specific and different from the surrounding water. Extensive mining of bacterial antiphage defense systems in the metagenomes revealed a variety of defense mechanisms. The abundance of defense systems was comparable in the metagenomes of the sponges and the surrounding water, thus distinguishing the White Sea sponges from those inhabiting the tropical seas. We developed a network-based approach for the combined analysis of CRISPR-spacers and protospacers. Using this approach, we showed that the virus–host interactions within the sponge-associated community are typically more abundant (three out of four interactions studied) than the inter-community interactions. Additionally, we detected the occurrence of viral exchanges between the communities. Our work provides the first insight into the metagenomics of the three cold-water sponge species from the White Sea and paves the way for a comprehensive analysis of the interactions between microbial communities and associated viruses. Full article

(This article belongs to the Special Issue Metagenomics: New Trends and Solutions)

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19 pages, 9865 KiB

Open AccessEditor’s ChoiceReview

Pediatric Neuromyelitis Optica Spectrum Disorder: Case Series and Literature Review

by Michela Ada Noris Ferilli, Roberto Paparella, Ilaria Morandini, Laura Papetti, Lorenzo Figà Talamanca, Claudia Ruscitto, Fabiana Ursitti, Romina Moavero, Giorgia Sforza, Samuela Tarantino, Martina Proietti Checchi, Federico Vigevano and Massimiliano Valeriani

Life 2022, 12(1), 19; https://doi.org/10.3390/life12010019 - 23 Dec 2021

Cited by 7 | Viewed by 5135

Abstract

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a central nervous system (CNS) inflammatory demyelinating disease characterized by recurrent inflammatory events that primarily involve optic nerves and the spinal cord, but also affect other regions of the CNS, including hypothalamus, area postrema and periaqueductal gray [...] Read more.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a central nervous system (CNS) inflammatory demyelinating disease characterized by recurrent inflammatory events that primarily involve optic nerves and the spinal cord, but also affect other regions of the CNS, including hypothalamus, area postrema and periaqueductal gray matter. The aquaporin-4 antibody (AQP4-IgG) is specific for NMOSD. Recently, myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) have been found in a group of AQP4-IgG negative patients. NMOSD is rare among children and adolescents, but early diagnosis is important to start adequate therapy. In this report, we present cases of seven pediatric patients with NMOSD and we review the clinical and neuroimaging characteristics, diagnosis, and treatment of NMOSD in children. Full article

(This article belongs to the Special Issue Research Updates in Pediatric Neuroscience)

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15 pages, 2432 KiB

Open AccessEditor’s ChoiceArticle

Major Surgical Trauma Impairs the Function of Natural Killer Cells but Does Not Affect Monocyte Cytokine Synthesis

by Roman M. Müller-Heck, Björn Bösken, Ivo Michiels, Marcel Dudda, Marcus Jäger and Stefanie B. Flohé

Life 2022, 12(1), 13; https://doi.org/10.3390/life12010013 - 22 Dec 2021

Cited by 6 | Viewed by 2828

Abstract

Major traumatic and surgical injury increase the risk for infectious complications due to immune dysregulation. Upon stimulation with interleukin (IL) 12 by monocyte/macrophages, natural killer (NK) cells release interferon (IFN) γ that supports the elimination of the pathogen. In the present study, we [...] Read more.

Major traumatic and surgical injury increase the risk for infectious complications due to immune dysregulation. Upon stimulation with interleukin (IL) 12 by monocyte/macrophages, natural killer (NK) cells release interferon (IFN) γ that supports the elimination of the pathogen. In the present study, we investigated the impact of invasive spine surgery on the relationship between monocytes and NK cells upon exposure to Staphylococcus aureus. Mononuclear cells and serum were isolated from peripheral blood of patients before and up to 8 d after surgery and stimulated with inactivated S. aureus bacteria. NK cell and monocyte function were determined by flow cytometry. NK cells continuously lost their ability to produce IFN-γ during the first week after surgery independently from monocyte-derived IL-12 secretion. IFN-γ synthesis was minimal on day 8 and was associated with decreased expression of the IL-12 receptor and activation of transcription factors required for IFNG gene transcription. Addition of recombinant IL-12 could at least partially restore NK cell function. Pre-operative levels of growth/differentiation factor (GDF) 15 in the serum correlated with the extent of NK cell suppression and with hospitalization. Thus, NK cell suppression after major surgery might represent a therapeutic target to improve the immune defense against opportunistic infections. Full article

(This article belongs to the Special Issue Healing after Trauma)

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9 pages, 538 KiB

Open AccessEditor’s ChoiceArticle

Posterior Circulation Endovascular Thrombectomy for Large Vessels Occlusion in Patients Presenting with NIHSS Score ≤ 10

by Andrea M. Alexandre, Iacopo Valente, Arturo Consoli, Pietro Trombatore, Luca Scarcia, Mariangela Piano, Nicola Limbucci, Joseph Domenico Gabrieli, Riccardo Russo, Antonio Armando Caragliano, Maria Ruggiero, Andrea Saletti, Guido Andrea Lazzarotti, Marco Pileggi, Mirco Cosottini, Fabio Pilato, Artur Slomka, Francesca Colò, Francesca Giubbolini, Giovanni Frisullo, Giacomo Della Marca, Aldobrando Broccolini and Alessandro Pedicelli Show full author list Hide full author list

Life 2021, 11(12), 1423; https://doi.org/10.3390/life11121423 - 17 Dec 2021

Cited by 18 | Viewed by 3232

Abstract

Mechanical thrombectomy (MT) is currently the gold standard treatment for ischemic stroke due to large vessel occlusion (LVO). However, the evidence of clinical usefulness of MT in posterior circulation LVO (pc-LVO) is still doubtful compared to the anterior circulation, especially in patients with [...] Read more.

Mechanical thrombectomy (MT) is currently the gold standard treatment for ischemic stroke due to large vessel occlusion (LVO). However, the evidence of clinical usefulness of MT in posterior circulation LVO (pc-LVO) is still doubtful compared to the anterior circulation, especially in patients with mild neurological symptoms. The database of 10 high-volume stroke centers in Europe, including a period of three year and a half, was screened for patients with an acute basilar artery occlusion or a single dominant vertebral artery occlusion (“functional” BAO) presenting with a NIHSS ≤10, and with at least 3 months follow-up. A total of 63 patients were included. Multivariate analysis demonstrated that female gender (adjusted OR 0.04; 95% CI 0–0.84; p = 0.04) and combined technique (adj OR 0.001; 95% CI 0–0.81; p = 0.04) were predictors of worse outcome. Higher pc-ASPECTS (adj OR 4.75; 95% CI 1.33–16.94; p = 0.02) and higher Delta NIHSS (adj OR 2.06; 95% CI 1.16–3.65; p = 0.01) were predictors of better outcome. Delta NIHSS was the main predictor of good outcome at 90 days in patients with posterior circulation LVO presenting with NIHSS score ≤ 10. Full article

(This article belongs to the Section Physiology and Pathology)

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12 pages, 639 KiB

Open AccessEditor’s ChoiceSystematic Review

Extracellular Vesicles in Pulmonary Fibrosis Models and Biological Fluids of Interstitial Lung Disease Patients: A Scoping Review

by Miriana d’Alessandro, Laura Bergantini, Elena Bargagli and Silvia Vidal

Life 2021, 11(12), 1401; https://doi.org/10.3390/life11121401 - 15 Dec 2021

Cited by 7 | Viewed by 3576

Abstract

Introduction: Interstitial lung diseases (ILDs) are a heterogeneous group of diffuse parenchymal lung disorders characterized by the pathogenetic involvement of interstitium. Therefore, an elucidation of the etiology and pathogenesis as well as the identification of diagnostic and prognostic biomarkers of such diseases is [...] Read more.

Introduction: Interstitial lung diseases (ILDs) are a heterogeneous group of diffuse parenchymal lung disorders characterized by the pathogenetic involvement of interstitium. Therefore, an elucidation of the etiology and pathogenesis as well as the identification of diagnostic and prognostic biomarkers of such diseases is more compelling than ever. It is of note that there is increasing evidence of the involvement of extracellular vesicles (EVs) in the pathogenesis of lung diseases including lung cancer, chronic obstructive pulmonary disease and pulmonary fibrosis. It has been speculated that EVs play a pivotal role as mediators of intercellular communication, as well as the highlighting of the role of EVs as co-operators in the development of lung diseases such as IPF. Methods: The present study aimed to carry out a systematic exploratory search of the literature (through the scoping review approach) to identify and systematize the main results of the pathogenetic role of EVs in pulmonary fibrosis models and biological fluids from ILD patients, including plasma, bronchoalveolar lavage (BAL) and sputum. Conclusion: Fibroblast-to-mesenchymal differentiation, collagen and extracellular matrix deposition are key mechanisms in the development and progression of IPF. EV-coupled miRNA are important modulators of biological processes in terms of intercellular communication as shown in pulmonary fibrosis models as well as biofluids. The helpfulness of EVs as diagnostic and theranostic markers is worth further investigation. The evolving potential of EVs to translate effective EV-based therapies into clinical practice is of growing interest, due to the urgent need for novel therapeutic strategies for IPF patients. Full article

(This article belongs to the Special Issue Advances in Theranostic Biomarkers in Lung Diseases)

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18 pages, 2890 KiB

Open AccessEditor’s ChoiceArticle

Prevalence of Vancomycin-Resistant Enterococci and Antimicrobial Residues in Wastewater and Surface Water

by Kristýna Hricová, Magdaléna Röderová, Petr Fryčák, Volodymyr Pauk, Ondřej Kurka, Kristýna Mezerová, Taťána Štosová, Jan Bardoň, David Milde, Pavla Kučová and Milan Kolář

Life 2021, 11(12), 1403; https://doi.org/10.3390/life11121403 - 15 Dec 2021

Cited by 11 | Viewed by 2836

Abstract

Due to the extensive use of antimicrobial agents in human and veterinary medicine, residues of various antimicrobials get into wastewater and, subsequently, surface water. On the one hand, a combination of processes in wastewater treatment plants aims to eliminate chemical and biological pollutants; [...] Read more.

Due to the extensive use of antimicrobial agents in human and veterinary medicine, residues of various antimicrobials get into wastewater and, subsequently, surface water. On the one hand, a combination of processes in wastewater treatment plants aims to eliminate chemical and biological pollutants; on the other hand, this environment may create conditions suitable for the horizontal transfer of resistance genes and potential selection of antibiotic-resistant bacteria. Wastewater and surface water samples (Morava River) were analyzed to determine the concentrations of 10 antibiotics and identify those exceeding so-called predicted no-effect environmental concentrations (PNECs). This study revealed that residues of five of the tested antimicrobials, namely ampicillin, clindamycin, tetracycline, tigecycline and vancomycin, in wastewater samples exceeded the PNEC. Vancomycin concentrations were analyzed with respect to the detected strains of vancomycin-resistant enterococci (VRE), in which the presence of resistance genes, virulence factors and potential relationship were analyzed. VRE were detected in 16 wastewater samples (11%) and two surface water samples (6%). The PNEC of vancomycin was exceed in 16% of the samples. Since the detected VRE did not correlate with the vancomycin concentrations, no direct relationship was confirmed between the residues of this antimicrobials and the presence of the resistant strains. Full article

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

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21 pages, 3488 KiB

Open AccessEditor’s ChoiceArticle

Diverse Effect of Two Cytokinins, Kinetin and Benzyladenine, on Plant Development, Biotic Stress Tolerance, and Gene Expression

by Zoltán Bozsó and Balázs Barna

Life 2021, 11(12), 1404; https://doi.org/10.3390/life11121404 - 15 Dec 2021

Cited by 9 | Viewed by 3436

Abstract

The plant hormones cytokinins affect a various array of plant growth and development processes as well as responses to biotic and abiotic stresses. In this study, the opposite effect of two different cytokinins kinetin (N⁶-furfuryladenine) and benzyladenine (BA) on development and [...] Read more.

The plant hormones cytokinins affect a various array of plant growth and development processes as well as responses to biotic and abiotic stresses. In this study, the opposite effect of two different cytokinins kinetin (N⁶-furfuryladenine) and benzyladenine (BA) on development and on the tolerance of Arabidopsis and tobacco plants to virus, bacteria, and fungi infection was reported. Treatments of Arabidopsis and tobacco seedlings with saturated solutions of BA inhibited plant progress, while treatments with saturated water solution of kinetin promoted plant development. Furthermore, BA pre-treatments strongly reduced the number of TMV (Tobacco mosaic virus) lesions on tobacco and the tissue damage caused by the incompatible Pseudomonas bacteria on Arabidopsis and tobacco leaves. Similarly, BA pre-treatment significantly reduced the necrotic disease symptoms of Botrytis cinerea infection. Kinetin pre-treatments had a much weaker or no protective effect on the damage caused by the above pathogens. Accordingly, Arabidopsis gene expression profiles after treatments also showed that the two cytokinins have different effects on several plant processes. The gene expression results supported the more robust effect of BA, which up and downregulated more than 2000 genes, while only 436 genes were influenced by kinetin treatment. It is noteworthy that BA and kinetin treatment changed gene expressions in the same direction only in a relatively few cases (73 upregulated and 70 downregulated genes), and even 28 genes were regulated into the opposite directions by BA and kinetin. Both treatments had a strong effect on auxin and gibberellin-related genes, but only BA had a significant effect on cytokinin-induced processes. While kinetin exclusively activated the flavonoid synthesis genes, BA affected more significantly protein synthesis, photosynthesis, and plant defence-related genes. In conclusion, BA solution had sometimes the opposite and generally a much stronger effect than kinetin solution not only on the development and on biotic stress tolerance of tobacco and Arabidopsis plants but also on the gene expressions. The stronger protective effect of BA to necrotic stresses is probably due to its stronger senescence inhibitory effect on plant tissues, as supported by the stronger chlorophyll retardation of the BA-treated leaves. Full article

(This article belongs to the Section Plant Science)

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19 pages, 1427 KiB

Open AccessEditor’s ChoiceReview

From Life in the Sea to the Clinic: The Marine Drugs Approved and under Clinical Trial

by Emiliano Cappello and Paola Nieri

Life 2021, 11(12), 1390; https://doi.org/10.3390/life11121390 - 11 Dec 2021

Cited by 32 | Viewed by 6136

Abstract

In the last decades Blue Growth policy in european and non-european countries produced a great impulse in applied marine sciences, comprehending the research of new bioactive molecules in marine organisms. These organisms are a great source of natural compounds with unique features resulting [...] Read more.

In the last decades Blue Growth policy in european and non-european countries produced a great impulse in applied marine sciences, comprehending the research of new bioactive molecules in marine organisms. These organisms are a great source of natural compounds with unique features resulting from the huge variability of marine habitats and species living in them. Most of the marine compounds in use and in clinical trials are drugs for cancer therapy and many of them are conjugated to antibody to form antibody-drug conjugates (ADCs). Severe pain, viral infections, hypertriglyceridemia, obesity, Alzheimer’s and other CNS diseases are further target conditions for these pharmaceuticals. This review summarizes the state-of-the-art marine drugs focusing on the most successful results in the fast expanding field of marine pharmacology. Full article

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

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15 pages, 736 KiB

Open AccessEditor’s ChoiceArticle

Risk Factors, Treatment and Prognosis of Patients with Lung Cancer after Heart Transplantation

by Karsten M. Heil, Matthias Helmschrott, Fabrice F. Darche, Tom Bruckner, Philipp Ehlermann, Michael M. Kreusser, Andreas O. Doesch, Wiebke Sommer, Gregor Warnecke, Norbert Frey and Rasmus Rivinius

Life 2021, 11(12), 1344; https://doi.org/10.3390/life11121344 - 4 Dec 2021

Cited by 4 | Viewed by 3082

Abstract

Long-term survival after heart transplantation (HTX) is impacted by adverse effects of immunosuppressive pharmacotherapy, and post-transplant lung cancer is a common occurrence. This study aimed to examine the risk factors, treatment, and prognosis of patients with post-transplant lung cancer. We included 625 adult [...] Read more.

Long-term survival after heart transplantation (HTX) is impacted by adverse effects of immunosuppressive pharmacotherapy, and post-transplant lung cancer is a common occurrence. This study aimed to examine the risk factors, treatment, and prognosis of patients with post-transplant lung cancer. We included 625 adult patients who received HTX at Heidelberg Heart Center between 1989 and 2018. Patients were stratified by diagnosis and staging of lung cancer after HTX. Analysis comprised donor and recipient characteristics, medications including immunosuppressive drugs, and survival after diagnosis of lung cancer. A total of 41 patients (6.6%) were diagnosed with lung cancer after HTX, 13 patients received curative care and 28 patients had palliative care. Mean time from HTX until diagnosis of lung cancer was 8.6 ± 4.0 years and 1.8 ± 2.7 years from diagnosis of lung cancer until last follow-up. Twenty-four patients (58.5%) were switched to an mTOR-inhibitor after diagnosis of lung cancer. Multivariate analysis showed recipient age (HR: 1.05; CI: 1.01–1.10; p = 0.02), COPD (HR: 3.72; CI: 1.88–7.37; p < 0.01), and history of smoking (HR: 20.39; CI: 2.73–152.13; p < 0.01) as risk factors for post-transplant lung cancer. Patients in stages I and II had a significantly better 1-year (100.0% versus 3.6%), 2-year (69.2% versus 0.0%), and 5-year survival (53.8% versus 0.0%) than patients in stages III and IV (p < 0.01). Given the poor prognosis of late-stage post-transplant lung cancer, routine reassessment of current smoking status, providing smoking cessation support, and intensified lung cancer screening in high-risk HTX recipients are advisable. Full article

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

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26 pages, 5141 KiB

Open AccessEditor’s ChoiceArticle

Clinical Relevance of Secreted Small Noncoding RNAs in an Embryo Implantation Potential Prediction at Morula and Blastocyst Development Stages

by Angelika V. Timofeeva, Ivan S. Fedorov, Maria A. Shamina, Vitaliy V. Chagovets, Nataliya P. Makarova, Elena A. Kalinina, Tatiana A. Nazarenko and Gennady T. Sukhikh

Life 2021, 11(12), 1328; https://doi.org/10.3390/life11121328 - 1 Dec 2021

Cited by 5 | Viewed by 2949

Abstract

Despite the improvements in biotechnological approaches and the selection of controlled ovarian hyperstimulation protocols, the resulting pregnancy rate from in vitro fertilization (IVF) protocols still does not exceed 30–40%. In this connection, there is an acute question of the development of a non-invasive, [...] Read more.

Despite the improvements in biotechnological approaches and the selection of controlled ovarian hyperstimulation protocols, the resulting pregnancy rate from in vitro fertilization (IVF) protocols still does not exceed 30–40%. In this connection, there is an acute question of the development of a non-invasive, sensitive, and specific method for assessing the implantation potential of an embryo. A total of 110 subfertile couples were included in the study to undergo the IVF/ICSI program. Obtained embryos for transfer into the uterine cavity of patient cohort 1 (n = 60) and cohort 2 (n = 50) were excellent/good-quality blastocysts, and small noncoding RNA (sncRNA) content in the corresponding spent culture medium samples at the morula stage (n = 43) or at the blastocyst stage (n = 31) was analyzed by deep sequencing followed by qRT-PCR in real time. Two logistic regression models were developed to predict the implantation potential of the embryo with 100% sensitivity and 100% specificity: model 1 at the morula stage, using various combinations of hsa_piR_022258, hsa-let-7i-5p, hsa_piR_000765, hsa_piR_015249, hsa_piR_019122, and hsa_piR_008112, and model 2 at the blastocyst stage, using various combinations of hsa_piR_020497, hsa_piR_008113, hsa-miR-381-3p, hsa_piR_022258, and hsa-let-7a-5p. Protein products of sncRNA potential target genes participate in the selective turnover of proteins through the ubiquitination system and in the organization of the various cell cytoskeleton and nucleoskeleton structures, regulating the activity of the Hippo signaling pathway, which determines the fate specification of the blastomers. Full article

(This article belongs to the Special Issue Genomic and Transcriptomic Alterations in Cancer and Aging)

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