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Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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Article

13 pages, 1606 KiB  
Article
The Role of the Precuneus in Human Spatial Updating in a Real Environment Setting—A cTBS Study
by Milos Dordevic, Sonja Hoelzer, Augusta Russo, José C. García Alanis and Notger G. Müller
Life 2022, 12(8), 1239; https://doi.org/10.3390/life12081239 - 15 Aug 2022
Cited by 5 | Viewed by 1794
Abstract
As we move through an environment, we update positions of our body relative to other objects, even when some objects temporarily or permanently leave our field of view—this ability is termed egocentric spatial updating and plays an important role in everyday life. Still, [...] Read more.
As we move through an environment, we update positions of our body relative to other objects, even when some objects temporarily or permanently leave our field of view—this ability is termed egocentric spatial updating and plays an important role in everyday life. Still, our knowledge about its representation in the brain is still scarce, with previous studies using virtual movements in virtual environments or patients with brain lesions suggesting that the precuneus might play an important role. However, whether this assumption is also true when healthy humans move in real environments where full body-based cues are available in addition to the visual cues typically used in many VR studies is unclear. Therefore, in this study we investigated the role of the precuneus in egocentric spatial updating in a real environment setting in 20 healthy young participants who underwent two conditions in a cross-over design: (a) stimulation, achieved through applying continuous theta-burst stimulation (cTBS) to inhibit the precuneus and (b) sham condition (activated coil turned upside down). In both conditions, participants had to walk back with blindfolded eyes to objects they had previously memorized while walking with open eyes. Simplified trials (without spatial updating) were used as control condition, to make sure the participants were not affected by factors such as walking blindfolded, vestibular or working memory deficits. A significant interaction was found, with participants performing better in the sham condition compared to real stimulation, showing smaller errors both in distance and angle. The results of our study reveal evidence of an important role of the precuneus in a real-environment egocentric spatial updating; studies on larger samples are necessary to confirm and further investigate this finding. Full article
(This article belongs to the Section Physiology and Pathology)
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14 pages, 5983 KiB  
Article
Modularity of the Human Musculoskeletal System: The Correlation between Functional Structures by Computer Tools Analysis
by Daniele Della Posta, Jacopo Junio Valerio Branca, Giulia Guarnieri, Cristiana Veltro, Alessandra Pacini and Ferdinando Paternostro
Life 2022, 12(8), 1186; https://doi.org/10.3390/life12081186 - 3 Aug 2022
Cited by 3 | Viewed by 2032
Abstract
Introduction: For many years, anatomical studies have been conducted with a shattered view of the body. Although the study of the different apparatuses provides a systemic view of the human body, the reconstruction of the complex network of anatomical structures is crucial for [...] Read more.
Introduction: For many years, anatomical studies have been conducted with a shattered view of the body. Although the study of the different apparatuses provides a systemic view of the human body, the reconstruction of the complex network of anatomical structures is crucial for the understanding of structural and functional integration. Aim: We used network analysis to investigate the connection between the whole-body osteo-myofascial structures of the human musculoskeletal system. Materials and Methods: The musculoskeletal network was performed using the aNETomy® anatomical network with the implementation of the open-source software Cytoscape for data entry. Results: The initial graph was applied with a network consisting of 2298 body parts (nodes) and 7294 links, representing the musculoskeletal system. Considering the same weighted and unweighted osteo-myofascial network, a different distribution was obtained, suggesting both a topological organization and functional behavior of the network structure. Conclusions: Overall, we provide a deeply detailed anatomical network map of the whole-body musculoskeletal system that can be a useful tool for the comprehensive understanding of every single structure within the complex morphological organization, which could be of particular interest in the study of rehabilitation of movement dysfunctions. Full article
(This article belongs to the Section Physiology and Pathology)
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12 pages, 321 KiB  
Article
Alzheimer’s Disease Risk Variant rs3865444 in the CD33 Gene: A Possible Role in Susceptibility to Multiple Sclerosis
by Juraj Javor, Mária Bucová, Vladimíra Ďurmanová, Dominika Radošinská, Zuzana Párnická, Daniel Čierny, Egon Kurča, Daniela Čopíková-Cudráková, Karin Gmitterová and Ivana Shawkatová
Life 2022, 12(7), 1094; https://doi.org/10.3390/life12071094 - 21 Jul 2022
Cited by 2 | Viewed by 2015
Abstract
Polymorphisms in genes encoding receptors that modulate the activity of microglia and macrophages are attractive candidates for participation in genetic susceptibility to multiple sclerosis (MS). The aims of the study were to (1) investigate the association between Alzheimer’s disease-linked variant rs3865444:C>A in the [...] Read more.
Polymorphisms in genes encoding receptors that modulate the activity of microglia and macrophages are attractive candidates for participation in genetic susceptibility to multiple sclerosis (MS). The aims of the study were to (1) investigate the association between Alzheimer’s disease-linked variant rs3865444:C>A in the CD33 gene and MS risk, (2) assess the effect of the strongest MS risk allele HLA-DRB1*15:01 on this association, and (3) analyze the correlation of rs3865444 with selected clinical phenotypes, i.e., age of onset and disease severity. CD33 rs3865444 was genotyped in a cohort of 579 patients and 1145 controls and its association with MS risk and clinical phenotypes was analyzed by logistic and linear regression analysis, respectively. Statistical evaluation revealed that rs3865444 reduces the risk of MS in the HLA-DRB1*15:01-positive subpopulation but not in the cohort negative for HLA-DRB1*15:01. A significant antagonistic epistasis between rs3865444 A and HLA-DRB1*15:01 alleles in the context of MS risk was detected by the interaction synergy factor analysis. Comparison of allele and genotype distribution between relapsing-remitting MS, secondary progressive MS, and control groups revealed that rs3865444 C to A substitution may also be associated with a decreased risk of transition of MS to its secondary progressive form, irrespective of the HLA-DRB1*15:01 carrier status. On the other hand, no correlation could be found between rs3865444 and the age of disease onset or MS severity score. Future studies are required to shed more light on the role of CD33 in MS pathogenesis. Full article
(This article belongs to the Special Issue Neurological Diseases: From Molecular Mechanisms to Therapy)
11 pages, 1201 KiB  
Article
Finding Emergent Gait Patterns May Reduce Progression of Knee Osteoarthritis in a Clinically Relevant Time Frame
by Dhruv Gupta, Cyril John Donnelly and Jeffrey A. Reinbolt
Life 2022, 12(7), 1050; https://doi.org/10.3390/life12071050 - 14 Jul 2022
Cited by 4 | Viewed by 2303
Abstract
A high contact force between the medial femoral condyle and the tibial plateau is the primary cause of medial compartment knee osteoarthritis (OA). A high medial contact force (MCF) during gait has been shown to be correlated to both the knee adduction moment [...] Read more.
A high contact force between the medial femoral condyle and the tibial plateau is the primary cause of medial compartment knee osteoarthritis (OA). A high medial contact force (MCF) during gait has been shown to be correlated to both the knee adduction moment (KAM) and knee flexion/extension moment (KFM). In this study, we used OpenSim Moco to find gait kinematics that reduced the peaks of the KAM, without increasing the peaks of the KFM, which could potentially reduce the MCF and, hence, the progression of knee OA. We used gait data from four knee OA participants. Our simulations decreased both peaks of the KAM without increasing either peak of the KFM. We found that increasing the step width was the primary mechanism, followed by simulations of all participants to reduce the frontal plane lever arm of the ground reaction force vector about the knee, in turn reducing the KAM. Importantly, each participant simulation followed different patterns of kinematic changes to achieve this reduction, which highlighted the need for participant-specific gait modifications. Moreover, we were able to simulate emerging gait patterns within 15 min, enhancing the relevance and potential for the application of developed methods in clinical settings. Full article
(This article belongs to the Special Issue The Biomechanics of Injury and Rehabilitation)
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14 pages, 1543 KiB  
Article
Combination of Two Manipulative Techniques for the Treatment of Cervicogenic Dizziness: A Randomized Controlled Trial
by Andoni Carrasco-Uribarren, Pilar Pardos-Aguilella, Silvia Pérez-Guillén, Carlos López-de-Celis, Jacobo Rodríguez-Sanz and Sara Cabanillas-Barea
Life 2022, 12(7), 1023; https://doi.org/10.3390/life12071023 - 9 Jul 2022
Cited by 2 | Viewed by 3018
Abstract
Cervicogenic dizziness is clinically associated with upper cervical spine dysfunctions. It seems that manual therapy decreases the intensity of dizziness in these subjects, but what happens to pain measured by pressure pain threshold (PPT) has not been studied. Purpose: analyze the short-term effects [...] Read more.
Cervicogenic dizziness is clinically associated with upper cervical spine dysfunctions. It seems that manual therapy decreases the intensity of dizziness in these subjects, but what happens to pain measured by pressure pain threshold (PPT) has not been studied. Purpose: analyze the short-term effects of combination two manipulation techniques protocol in worst dizziness intensity (wVAS), dizziness and cervical disability, upper cervical spine mobility and mechanosensivity of cervical tissue. Methods: Assessor-blinded randomized controlled trial was developed. A total of 40 patients with cervicogenic dizziness were randomly divided into two groups. The experimental group received three treatments consisting of a functional massage and a manipulation technique, and compared with a control group. The wVAS, dizziness handicap inventory (DHI), neck disability index (NDI), UCS mobility, and PPTs were measured. Measurements were made at the baseline, first follow-up 48 h after intervention and second follow-up 1 month after the intervention. Results: at second follow-up wVAS (p < 0.001), NDI (p < 0.001), DHI (p < 0.001), and upper right trapezius (p < 0.022) and right suboccipital (p < 0.043) PPTs showed a difference between groups in favor of the experimental group. Conclusions: apparently, the proposed intervention protocol decreases the intensity of dizziness and the mechanosensitivity of the cervical tissue and improves the feeling of disability due to neck pain and dizziness. Full article
(This article belongs to the Special Issue The Biomechanics of Injury and Rehabilitation)
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8 pages, 255 KiB  
Article
Fever Correlation with Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) Concentrations in Patients with Isolated Polymyalgia Rheumatica (PMR): A Retrospective Comparison Study between Hospital and Out-of-Hospital Local Registries
by Ciro Manzo, Marcin Milchert, Carlo Venditti, Alberto Castagna, Arvind Nune, Maria Natale and Marek Brzosko
Life 2022, 12(7), 985; https://doi.org/10.3390/life12070985 - 30 Jun 2022
Cited by 1 | Viewed by 2455
Abstract
Background: Polymyalgia rheumatica (PMR) is the most common systemic inflammatory rheumatic disease affecting the elderly. Giant cell arteritis (GCA) is a granulomatous vasculitis affecting the aorta and its branches associated with PMR in up to 20% of cases. In recent studies based on [...] Read more.
Background: Polymyalgia rheumatica (PMR) is the most common systemic inflammatory rheumatic disease affecting the elderly. Giant cell arteritis (GCA) is a granulomatous vasculitis affecting the aorta and its branches associated with PMR in up to 20% of cases. In recent studies based on university hospital registries, fever correlated with the erythrocyte sedimentation rate (ESR) but not with C-reactive protein (CRP) concentrations at the time of diagnosis in patients with isolated PMR. A long delay to a PMR diagnosis was suggested to explain this discrepancy, possibly caused by laboratory alterations (for instance, anemia of chronic disease type) that can influence only ESR. We performed a retrospective comparison study between the university hospital and two out-of-hospital public ambulatory databases, searching for any differences in fever/low-grade fever correlation with ESR and CRP. Methods: We identified all patients with newly diagnosed PMR between 2013 and 2020, only including patients who had a body temperature (BT) measurement at the time of diagnosis and a follow-up of at least two years. We considered BT as normal at <37.2 °C. Routine diagnostic tests for differential diagnostics were performed at the time of diagnosis and during follow-ups, indicating the need for more in-depth investigations if required. The GCA was excluded based on the presence of suggestive signs or symptoms and routine ultrasound examination of temporal, axillary, subclavian, and carotid arteries by experienced ultrasonographers. Patients with malignancies, chronic renal disease, bacterial infections, and body mass index (BMI) > 30 kg/m2 were excluded, as these conditions can increase CRP and/or ESR. Finally, we used the Cumulative Illness Rating Scale (CIRS) for quantifying the burden of comorbidities and excluded patients with a CIRS index > 4 as an additional interfering factor. Results: We evaluated data from 169 (73 from hospital and 96 from territorial registries) patients with newly diagnosed isolated PMR. Among these, 77.7% were female, and 61.5% of patients had normal BT at the time of diagnosis. We divided the 169 patients into two cohorts (hospital and territorial) according to the first diagnostic referral. Age at diagnosis, ESR, CRP, median hemoglobin (HB), and diagnostic delay (days from first manifestations to final diagnosis) were statistically significantly different between the two cohorts. However, when we assessed these data according to BT in the territorial cohort, we found a statistical difference only between ESR and BT (46.39 ± 19.31 vs. 57.50 ± 28.16; p = 0.026). Conclusions: ESR but not CRP correlates with fever/low-grade fever at the time of diagnosis in PMR patients with a short diagnosis delay regardless of HB levels. ESR was the only variable having a statistically significant correlation with BT in a multilevel regression analysis adjusted for cohorts (β = 0.312; p = 0.014). Full article
(This article belongs to the Special Issue Innovative Biomarker and Precision Medicine)
12 pages, 1215 KiB  
Article
How Is CYP17A1 Activity Altered in Autism? A Pilot Study to Identify Potential Pharmacological Targets
by Benedikt Andreas Gasser, Johann Kurz, Bernhard Dick and Markus Georg Mohaupt
Life 2022, 12(6), 867; https://doi.org/10.3390/life12060867 - 10 Jun 2022
Cited by 1 | Viewed by 2098
Abstract
Background: Increasing evidence exists that higher levels of androgens can be found in individuals with autism. Evidence yields to a susceptible role of Cytochrome P450 17A1 (CYP17A1) with its catalyzation of the two distinct types of substrate oxidation by a hydroxylase activity (17-alpha [...] Read more.
Background: Increasing evidence exists that higher levels of androgens can be found in individuals with autism. Evidence yields to a susceptible role of Cytochrome P450 17A1 (CYP17A1) with its catalyzation of the two distinct types of substrate oxidation by a hydroxylase activity (17-alpha hydroxylase) and C17/20 lyase activity. However, to what extent steps are altered in affected children with autism versus healthy controls remains to be elucidated. Methods: Urine samples from 48 boys with autism (BMI 19.1 ± 0.6 kg/m2, age 14.2 ± 0.5 years) and a matched cohort of 48 healthy boys (BMI 18.6 ± 0.3 kg/m2, 14.3 ± 0.5 years) as well as 16 girls with autism (BMI 17.5 ± 0.7 kg/m2, age 13.8 ± 1.0 years) and a matched cohort of 16 healthy girls (BMI 17.2 ± 0.8 kg/m2, age 13.2 ± 0.8 years) were analyzed for steroid hormone metabolites by gas chromatography-mass spectrometry. Results: The activity of 17-alpha Hydroxylase increased by almost 50%, whereas activity of 17/20 Lyase activity increased by around 150% in affected children with autism. Furthermore, the concentration of Cortisol was higher as compared to the average increase of the three metabolites TH-Corticosterone, 5α-TH-Corticosterone and TH-11β-DH-Corticosterone, indicating, in addition, a stimulation by the CRH-ACTH system despite a higher enzymatic activity. Discussion: As it was shown that oxidative stress increases the 17/20-lyase activity via p38α, a link between higher steroid hormone levels and oxidative stress can be established. However, as glucocorticoid as well as androgen metabolites showed higher values in subjects affected with autism as compared to healthy controls, the data indicate, despite higher CYP17A1 activity, the presence of increased substrate availability in line with the Cholesterol theory of autism. Full article
(This article belongs to the Section Physiology and Pathology)
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12 pages, 4381 KiB  
Article
A Seed-Borne Bacterium of Rice, Pantoea dispersa BB1, Protects Rice from the Seedling Rot Caused by the Bacterial Pathogen Burkholderia glumae
by Yusuke Kouzai and Chiharu Akimoto-Tomiyama
Life 2022, 12(6), 791; https://doi.org/10.3390/life12060791 - 26 May 2022
Cited by 8 | Viewed by 3237
Abstract
Seedling rot, caused by the bacterial pathogen Burkholderia glumae, is a major disease of rice. It originates from pathogen-contaminated seeds and is thus mainly controlled by pesticide treatments of seeds. We previously demonstrated that the seed-borne bacteria of rice may be a [...] Read more.
Seedling rot, caused by the bacterial pathogen Burkholderia glumae, is a major disease of rice. It originates from pathogen-contaminated seeds and is thus mainly controlled by pesticide treatments of seeds. We previously demonstrated that the seed-borne bacteria of rice may be a useful and sustainable alternative to pesticides to manage seedling rot, but they are limited in terms of variety. Here, we report that another seed-borne bacterium, Pantoea dispersa BB1, protects rice from B. glumae. We screened 72 bacterial isolates from rice seeds of three genetically different cultivars inoculated or non-inoculated with B. glumae. 16S rRNA gene sequencing revealed that pathogen inoculation affected the composition of culturable seed-borne bacterial communities and increased the presence of Pantoea and Paenibacillus species. Among three Pantoea and Paenibacillus isolates that exhibit tolerance to toxoflavin, a virulence factor of B. glumae, P. dispersa BB1 significantly mitigated the symptoms of rice seedling rot. The culture filtrate of BB1 inhibited the growth of B. glumae in vitro, suggesting that this isolate secretes antibacterial compounds. Seed treatment with BB1 suppressed pathogen propagation in plants, although seed treatment with the culture filtrate did not. Because BB1 did not show pathogenicity in rice, our findings demonstrate that BB1 is a promising biocontrol agent against seedling rot. Full article
(This article belongs to the Collection State of the Art in Plant Science)
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15 pages, 3321 KiB  
Article
Role of SaPCR2 in Zn Uptake in the Root Elongation Zone of the Zn/Cd Hyperaccumulator Sedum alfredii
by Jun Ge, Jiayu Lin, Zhiying Wu, Kuan Xu, Jingyu Tao, Haizhong Lin, Shengke Tian and Lingli Lu
Life 2022, 12(5), 768; https://doi.org/10.3390/life12050768 - 23 May 2022
Viewed by 1852
Abstract
Zn pollution is a potential toxicant for agriculture and the environment. Sedum alfredii is a Zn/Cd hyperaccumulator found in China and has been proven as a useful resource for the phytoremediation of Zn-contaminated sites. However, the molecular mechanism of Zn uptake in S. [...] Read more.
Zn pollution is a potential toxicant for agriculture and the environment. Sedum alfredii is a Zn/Cd hyperaccumulator found in China and has been proven as a useful resource for the phytoremediation of Zn-contaminated sites. However, the molecular mechanism of Zn uptake in S. alfredii is limited. In this study, the function of SaPCR2 on Zn uptake in S. alfredii was identified by gene expression analysis, yeast function assays, Zn accumulation and root morphology analysis in transgenic lines to further elucidate the mechanisms of uptake and translocation of Zn in S. alfredii. The results showed that SaPCR2 was highly expressed in the root elongation zone of the hyperaccumulating ecotype (HE) S. alfredii, and high Zn exposure downregulated the expression of SaPCR2 in the HE S. alfredii root. The heterologous expression of SaPCR2 in yeast suggested that SaPCR2 was responsible for Zn influx. The overexpression of SaPCR2 in the non-hyperaccumulating ecotype (NHE) S. alfredii significantly increased the root uptake of Zn, but did not influence Mn, Cu or Fe. SR-μ-XRF technology showed that more Zn was distributed in the vascular buddle tissues, as well as in the cortex and epidermis in the transgenic lines. Root morphology was also altered after SaPCR2 overexpression, and a severe inhibition was observed. In the transgenic lines, the meristematic and elongation zones of the root were lower compared to the WT, and Zn accumulation in meristem cells was also reduced. These results indicate that SaPCR2 is responsible for Zn uptake, and mainly functions in the root elongation zone. This research on SaPCR2 could provide a theoretical basis for the use of genetic engineering technology in the modification of crops for their safe production and biological enhancement. Full article
(This article belongs to the Special Issue Uptake, Translocation, and Metabolism of Trace Metals in Plants)
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17 pages, 1398 KiB  
Article
SIRT1: Genetic Variants and Serum Levels in Age-Related Macular Degeneration
by Kriste Kaikaryte, Greta Gedvilaite, Alvita Vilkeviciute, Loresa Kriauciuniene, Ruta Mockute, Dzastina Cebatoriene, Reda Zemaitiene, Vilma Jurate Balciuniene and Rasa Liutkeviciene
Life 2022, 12(5), 753; https://doi.org/10.3390/life12050753 - 19 May 2022
Cited by 3 | Viewed by 2144
Abstract
Background: The aim of this paper was to determine the frequency of SIRT1 rs3818292, rs3758391, rs7895833 single nucleotide polymorphism genotypes and SIRT1 serum levels associated with age-related macular degeneration (AMD) in the Lithuanian population. Methods: Genotyping of SIRT1 rs3818292, rs3758391 and rs7895833 was [...] Read more.
Background: The aim of this paper was to determine the frequency of SIRT1 rs3818292, rs3758391, rs7895833 single nucleotide polymorphism genotypes and SIRT1 serum levels associated with age-related macular degeneration (AMD) in the Lithuanian population. Methods: Genotyping of SIRT1 rs3818292, rs3758391 and rs7895833 was performed using RT-PCR. SIRT1 serum level was determined using the ELISA method. Results: We found that rs3818292 and rs7895833 were associated with an increased risk of developing exudative AMD. Additional sex-differentiated analysis revealed only rs7895833 was associated with an increased risk of developing exudative AMD in women after strict Bonferroni correction. The analysis also revealed that individuals carrying rs3818292, rs3758391 and rs7895833 haplotype G-T-G are associated with increased odds of exudative AMD. Still, the rare haplotypes were associated with the decreased odds of exudative AMD. After performing an analysis of serum SIRT1 levels and SIRT1 genetic variant, we found that carriers of the SIRT1 rs3818292 minor allele G had higher serum SIRT1 levels than the AA genotype. In addition, individuals carrying at least one SIRT1 rs3758391 T allele also had elevated serum SIRT1 levels compared with individuals with the wild-type CC genotype. Conclusions: Our study showed that the SIRT1 polymorphisms rs3818292 and rs7895833 and rs3818292-rs3758391-rs7895833 haplotype G-T-G could be associated with the development of exudative AMD. Also, two SNPs (rs3818292 and rs3758391) are associated with elevated SIRT1 levels. Full article
(This article belongs to the Special Issue Age-Related Macular Degeneration: From Mechanisms to Therapy)
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13 pages, 6581 KiB  
Article
Diffusion Tensor Imaging of a Median Nerve by Magnetic Resonance: A Pilot Study
by Kanza Awais, Žiga Snoj, Erika Cvetko and Igor Serša
Life 2022, 12(5), 748; https://doi.org/10.3390/life12050748 - 18 May 2022
Cited by 3 | Viewed by 2156
Abstract
The magnetic resonance Diffusion Tensor Imaging (DTI) is a powerful extension of Diffusion Weighted Imaging (DWI) utilizing multiple bipolar gradients, allowing for the evaluation of the microstructural environment of the highly anisotropic tissues. DTI was predominantly used for the assessment of the central [...] Read more.
The magnetic resonance Diffusion Tensor Imaging (DTI) is a powerful extension of Diffusion Weighted Imaging (DWI) utilizing multiple bipolar gradients, allowing for the evaluation of the microstructural environment of the highly anisotropic tissues. DTI was predominantly used for the assessment of the central nervous system (CNS), but with the advancement in magnetic resonance (MR) hardware and software, it has now become possible to image the peripheral nerves which were difficult to evaluate previously because of their small caliber. This study focuses on the assessment of the human median peripheral nerve ex vivo by DTI microscopy at 9.4 T magnetic field which allowed the evaluation of diffusion eigenvalues, the mean diffusivity and the fractional anisotropy at 35 μm in-plane resolution. The resolution was sufficient for clear depiction of all nerve anatomical structures and therefore further image analysis allowed the obtaining of average values for DT parameters in nerve fascicles (intrafascicular region and perineurium) as well as in the surrounding epineurium. The results confirmed the highest fractional anisotropy of 0.33 and principal diffusion eigenvalue of 1.0 × 10−9 m2/s in the intrafascicular region, somewhat lower values of 0.27 and 0.95 × 10−9 m2/s in the perineurium region and close to isotropic with very slow diffusion (0.15 and 0.05 × 10−9 m2/s) in the epineurium region. Full article
(This article belongs to the Special Issue Imaging in Neurosurgery: State of the Art)
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12 pages, 5462 KiB  
Article
Variations in Strain Distribution at Distal Radius under Different Loading Conditions
by Jonas A. Pramudita, Wataru Hiroki, Takuya Yoda and Yuji Tanabe
Life 2022, 12(5), 740; https://doi.org/10.3390/life12050740 - 16 May 2022
Cited by 3 | Viewed by 3802
Abstract
Distal radial fractures exhibit various fracture patterns. By assuming that the strain distribution at the distal radius affects the diversification of the fracture pattern, a parameter study using the finite element model of a wrist developed from computed tomography (CT) images was performed [...] Read more.
Distal radial fractures exhibit various fracture patterns. By assuming that the strain distribution at the distal radius affects the diversification of the fracture pattern, a parameter study using the finite element model of a wrist developed from computed tomography (CT) images was performed under different loading conditions. The finite element model of the wrist consisted of the radius, ulna, scaphoid, lunate, triquetrum, and major carpal ligaments. The material properties of the bone models were assigned on the basis of the Hounsfield Unit (HU) values of the CT images. An impact load was applied to the scaphoid, lunate, and triquetrum to simulate boundary conditions during fall accidents. This study considered nine different loading conditions that combine three different loading directions and three different load distribution ratios. According to the analysis results, the strain distribution at the distal radius changed with respect to the change in the loading condition. High strain concentration occurred in regions where distal radius fractures are commonly developed. The direction and distribution of the load acting on the radius were considered to be factors that may cause variations in the fracture pattern of distal radius fractures. Full article
(This article belongs to the Special Issue The Biomechanics of Injury and Rehabilitation)
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17 pages, 1115 KiB  
Article
Antimicrobial Properties of Compounds Isolated from Syzygium malaccense (L.) Merr. and L.M. Perry and Medicinal Plants Used in French Polynesia
by Camille Quenon, Thierry Hennebelle, Jean-François Butaud, Raimana Ho, Jennifer Samaillie, Christel Neut, Tamatoa Lehartel, Céline Rivière, Ali Siah, Natacha Bonneau, Sevser Sahpaz, Sébastien Anthérieu, Nicolas Lebegue, Phila Raharivelomanana and Vincent Roumy
Life 2022, 12(5), 733; https://doi.org/10.3390/life12050733 - 14 May 2022
Cited by 8 | Viewed by 3401
Abstract
A preliminary ethnopharmacological survey, achieved in French Polynesia, led to the collection of the most cited plants among 63 species used to treat “infectious” diseases, with a description of their medicinal uses. Bibliographical investigations and antimicrobial screening permitted the selection of the botanical [...] Read more.
A preliminary ethnopharmacological survey, achieved in French Polynesia, led to the collection of the most cited plants among 63 species used to treat “infectious” diseases, with a description of their medicinal uses. Bibliographical investigations and antimicrobial screening permitted the selection of the botanical species Syzygium malaccense (Myrtaceae) for phytochemical analysis. Leaves of Syzygium malaccense were usually used in mixture with rhizomes of Curcuma longa to treat infectious diseases such as cystitis. The methanolic plant extracts were tested in vitro with an agar microdilution method on 33 bacteria strains and 1 yeast to obtain their Minimal Inhibitory Concentration (MIC), and cytotoxicity against HepG2 cells were evaluated. Antimicrobial synergistic effects of methanolic plant extracts from leaves of Syzygium malaccense and rhizomes from Curcuma longa were also evaluated. The bio-guided isolation of leaf extract from Syzygium malaccense led to the identification of seven alkyl-salicylic acids (anacardic acids or ginkgolic acids C15:0, C15:1, C17:0, C17:1, C17:2, C17:3 and C19:1) described for the first time in this species. All compounds were tested against Staphylococcus aureus (18.75 < MIC < 75.0 µg/mL), Streptococcus pyogenes (2.34 < MIC < 18.75 µg/mL) and Pseudomonas aeruginosa (MIC = 150 µg/mL), and their structure–activity relationships were discussed. The methanolic extract and salicylic derivatives from S. malaccense showed an interesting antimicrobial activity against Gram+ bacteria, without toxicity on hepG2 cells at 400 μg/mL. Moreover, these antibacterial compounds have already been studied for their anti-inflammatory activity, which supports the therapeutic interest of S. malaccense against infectious diseases. Full article
(This article belongs to the Section Plant Science)
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15 pages, 2842 KiB  
Article
Data Mining Identifies CCN2 and THBS1 as Biomarker Candidates for Cardiac Hypertrophy
by Markus Johansson, Benyapa Tangruksa, Sepideh Heydarkhan-Hagvall, Anders Jeppsson, Peter Sartipy and Jane Synnergren
Life 2022, 12(5), 726; https://doi.org/10.3390/life12050726 - 12 May 2022
Cited by 4 | Viewed by 3398
Abstract
Cardiac hypertrophy is a condition that may contribute to the development of heart failure. In this study, we compare the gene-expression patterns of our in vitro stem-cell-based cardiac hypertrophy model with the gene expression of biopsies collected from hypertrophic human hearts. Twenty-five differentially [...] Read more.
Cardiac hypertrophy is a condition that may contribute to the development of heart failure. In this study, we compare the gene-expression patterns of our in vitro stem-cell-based cardiac hypertrophy model with the gene expression of biopsies collected from hypertrophic human hearts. Twenty-five differentially expressed genes (DEGs) from both groups were identified and the expression of selected corresponding secreted proteins were validated using ELISA and Western blot. Several biomarkers, including CCN2, THBS1, NPPA, and NPPB, were identified, which showed significant overexpressions in the hypertrophic samples in both the cardiac biopsies and in the endothelin-1-treated cells, both at gene and protein levels. The protein-interaction network analysis revealed CCN2 as a central node among the 25 overlapping DEGs, suggesting that this gene might play an important role in the development of cardiac hypertrophy. GO-enrichment analysis of the 25 DEGs revealed many biological processes associated with cardiac function and the development of cardiac hypertrophy. In conclusion, we identified important similarities between ET-1-stimulated human-stem-cell-derived cardiomyocytes and human hypertrophic cardiac tissue. Novel putative cardiac hypertrophy biomarkers were identified and validated on the protein level, lending support for further investigations to assess their potential for future clinical applications. Full article
(This article belongs to the Special Issue The Molecular Mechanism of Cardiovascular Disease)
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16 pages, 6005 KiB  
Article
Biogas Production Potential of Thermophilic Anaerobic Biodegradation of Organic Waste by a Microbial Consortium Identified with Metagenomics
by Lyudmila Kabaivanova, Penka Petrova, Venelin Hubenov and Ivan Simeonov
Life 2022, 12(5), 702; https://doi.org/10.3390/life12050702 - 8 May 2022
Cited by 15 | Viewed by 2751
Abstract
Anaerobic digestion (AD) is a widespread biological process treating organic waste for green energy production. In this study, wheat straw and corn stalks without any harsh preliminary treatment were collected as a renewable source to be employed in a laboratory-scale digester to produce [...] Read more.
Anaerobic digestion (AD) is a widespread biological process treating organic waste for green energy production. In this study, wheat straw and corn stalks without any harsh preliminary treatment were collected as a renewable source to be employed in a laboratory-scale digester to produce biogas/biomethane. Processes parameters of temperature, pH, total solids, volatile solid, concentration of volatile fatty acids (VFA), and cellulose concentration, were followed. The volume of biogas produced was measured. The impact of organic loading was stated, showing that the process at 55 °C tolerated a higher substrate load, up to 45 g/L. Further substrate increase did not lead to biogas accumulation increase, probably due to inhibition or mass transfer limitations. After a 12-day anaerobic digestion process, cumulative volumes of biogas yields were 4.78 L for 1 L of the bioreactor working volume with substrate loading 30 g/L of wheat straw, 7.39 L for 40 g/L and 8.22 L for 45 g/L. The degree of biodegradation was calculated to be 68.9%, 74% and 72%, respectively. A fast, effective process for biogas production was developed from native wheat straw, with the highest quantity of daily biogas production occurring between day 2 and day 5. Biomethane concentration in the biogas was 60%. An analysis of bacterial diversity by metagenomics revealed that more than one third of bacteria belonged to class Clostridia (32.9%), followed by Bacteroidia (21.5%), Betaproteobacteria (11.2%), Gammaproteobacteria (6.1%), and Alphaproteobacteria (5%). The most prominent genera among them were Proteiniphilum, Proteiniborus, and Pseudomonas. Archaeal share was 1.37% of the microflora in the thermophilic bioreactor, as the genera Methanocorpusculum, Methanobacterium, Methanomassiliicoccus, Methanoculleus, and Methanosarcina were the most abundant. A knowledge of the microbiome residing in the anaerobic digester can be further used for the development of more effective processes in conjunction with theidentified consortium. Full article
(This article belongs to the Special Issue The Role of Renewable Resources for Ecology and Human Health)
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12 pages, 2527 KiB  
Article
Type 2 Diabetes Mellitus Facilitates Shift of Adipose-Derived Stem Cells Ex Vivo Differentiation toward Osteogenesis among Patients with Obesity
by Margarita Agareva, Iurii Stafeev, Svetlana Michurina, Igor Sklyanik, Ekaterina Shestakova, Elizaveta Ratner, Xiang Hu, Mikhail Menshikov, Marina Shestakova and Yelena Parfyonova
Life 2022, 12(5), 688; https://doi.org/10.3390/life12050688 - 6 May 2022
Cited by 6 | Viewed by 2781
Abstract
Objective: Sedentary behavior with overnutrition provokes the development of obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). The main progenitor cells of adipose tissue are adipose-derived stem cells (ADSCs) which can change differentiation, metabolic, and secretory phenotypes under obesity conditions. The purpose [...] Read more.
Objective: Sedentary behavior with overnutrition provokes the development of obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). The main progenitor cells of adipose tissue are adipose-derived stem cells (ADSCs) which can change differentiation, metabolic, and secretory phenotypes under obesity conditions. The purpose of this study was to evaluate ADSC osteogenesis activity among patients with obesity in normal glucose tolerance (NGT) and T2DM conditions. Methods: In the study, ADSCs from donors with obesity were used. After clinical characterization, all patients underwent bariatric surgery and ADSCs were isolated from subcutaneous fat biopsies. ADSCs were subjected to osteogenic differentiation, stained with Alizarin Red S, and harvested for real-time PCR and Western blotting. Cell senescence was evaluated with a β-galactosidase-activity-based assay. Results: Our results demonstrated the significantly increased calcification of ADSC on day 28 of osteogenesis in the T2DM group. These data were confirmed by the statistically significant enhancement of RUNX2 gene expression, which is a master regulator of osteogenesis. Protein expression analysis showed the increased expression of syndecan 1 and collagen I before and during osteogenesis, respectively. Moreover, T2DM ADSCs demonstrated an increased level of cellular senescence. Conclusion: We suggest that T2DM-associated cellular senescence can cause ADSC differentiation to shift toward osteogenesis, the impaired formation of new fat depots in adipose tissue, and the development of insulin resistance. The balance between ADSC adipo- and osteogenesis commitment is crucial for the determination of the metabolic fate of patients and their adipose tissue. Full article
(This article belongs to the Special Issue Diabetes Metabolism: Molecular and Integrative Approaches)
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24 pages, 6365 KiB  
Article
The Antileukemic and Anti-Prostatic Effect of Aeroplysinin-1 Is Mediated through ROS-Induced Apoptosis via NOX Activation and Inhibition of HIF-1a Activity
by Shou-Ping Shih, Mei-Chin Lu, Mohamed El-Shazly, Yu-Hsuan Lin, Chun-Lin Chen, Steve Sheng-Fa Yu and Yi-Chang Liu
Life 2022, 12(5), 687; https://doi.org/10.3390/life12050687 - 5 May 2022
Cited by 13 | Viewed by 2943
Abstract
Aeroplysinin-1 is a brominated isoxazoline alkaloid that has exhibited a potent antitumor cell effect in previous reports. We evaluated the cytotoxicity of aeroplysinin-1 against leukemia and prostate cancer cells in vitro. This marine alkaloid inhibited the cell proliferation of leukemia Molt-4, K562 cells, [...] Read more.
Aeroplysinin-1 is a brominated isoxazoline alkaloid that has exhibited a potent antitumor cell effect in previous reports. We evaluated the cytotoxicity of aeroplysinin-1 against leukemia and prostate cancer cells in vitro. This marine alkaloid inhibited the cell proliferation of leukemia Molt-4, K562 cells, and prostate cancer cells Du145 and PC-3 with IC50 values of 0.12 ± 0.002, 0.54 ± 0.085, 0.58 ± 0.109 and 0.33 ± 0.042 µM, respectively, as shown by the MTT assay. Furthermore, in the non-malignant cells, CCD966SK and NR8383, its IC50 values were 1.54 ± 0.138 and 6.77 ± 0.190 μM, respectively. In a cell-free system, the thermal shift assay and Western blot assay verified the binding affinity of aeroplysinin-1 to Hsp90 and Topo IIα, which inhibited their activity. Flow cytometry analysis showed that the cytotoxic effect of aeroplysinin-1 is mediated through mitochondria-dependent apoptosis induced by reactive oxygen species (ROS). ROS interrupted the cellular oxidative balance by activating NOX and inhibiting HIF-1α and HO-1 expression. Pretreatment with N-acetylcysteine (NAC) reduced Apl-1-induced mitochondria-dependent apoptosis and preserved the expression of NOX, HO-1, and HIF-1a. Our findings indicated that aeroplysinin-1 targeted leukemia and prostate cancer cells through multiple pathways, suggesting its potential application as an anti-leukemia and prostate cancer drug lead. Full article
(This article belongs to the Section Pharmaceutical Science)
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10 pages, 1246 KiB  
Article
N-Methyl-D-Aspartate (NMDA) Receptors in the Prelimbic Cortex Are Required for Short- and Long-Term Memory Formation in Trace Fear Conditioning
by Eui-Ho Park, Nam-Soo Kim, Yeon-Kyung Lee and June-Seek Choi
Life 2022, 12(5), 672; https://doi.org/10.3390/life12050672 - 1 May 2022
Cited by 2 | Viewed by 2925
Abstract
Accumulating evidence suggests that the medial prefrontal cortex (mPFC) has been implicated in the acquisition of fear memory during trace fear conditioning in which a conditional stimulus (CS) is paired with an aversive unconditional stimulus (UCS) separated by a temporal gap (trace interval, [...] Read more.
Accumulating evidence suggests that the medial prefrontal cortex (mPFC) has been implicated in the acquisition of fear memory during trace fear conditioning in which a conditional stimulus (CS) is paired with an aversive unconditional stimulus (UCS) separated by a temporal gap (trace interval, TI). However, little is known about the role of the prefrontal cortex for short- and long-term trace fear memory formation. Thus, we investigated how the prelimbic (PL) subregion within mPFC in rats contributes to short- and long-term trace fear memory formation using electrolytic lesions and d,l,-2-amino-5-phosphonovaleric acid (APV), an N-methyl-D-aspartate receptor (NMDAR) antagonist infusions into PL. In experiment 1, pre-conditioning lesions of PL impaired freezing to the CS as well as TI during the acquisition and retrieval sessions, indicating that PL is critically involved in trace fear memory formation. In experiment 2, temporary blockade of NMDA receptors in PL impaired the acquisition, but not the expression of short- and long-term trace fear memory. In addition, the inactivation of NMDAR in PL had little effect on locomotor activity, pre-pulse inhibition (PPI), or shock sensitivity. Taken together, these results suggest that NMDA receptor-mediated neurotransmission in PL is required for the acquisition of trace fear memory. Full article
(This article belongs to the Special Issue Glutamate Receptors)
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14 pages, 3769 KiB  
Article
Curcumin Protects Diabetic Mice against Isoproterenol-Induced Myocardial Infarction by Modulating CB2 Cannabinoid Receptors
by Harshal D. Pawar, Umesh B. Mahajan, Kartik T. Nakhate, Yogeeta O. Agrawal, Chandragouda R. Patil, M. F. Nagoor Meeran, Charu Sharma, Shreesh Ojha and Sameer N. Goyal
Life 2022, 12(5), 624; https://doi.org/10.3390/life12050624 - 22 Apr 2022
Cited by 17 | Viewed by 3138
Abstract
Molecular docking revealed curcumin as a potent CB2 cannabinoid receptor (CB2R) agonist. Since CB2R is involved in cardioprotective functions, we explored its role in ameliorative actions of curcumin against myocardial damage triggered by isoproterenol in diabetic animals. Mice were kept on a high-fat [...] Read more.
Molecular docking revealed curcumin as a potent CB2 cannabinoid receptor (CB2R) agonist. Since CB2R is involved in cardioprotective functions, we explored its role in ameliorative actions of curcumin against myocardial damage triggered by isoproterenol in diabetic animals. Mice were kept on a high-fat diet (HFD) throughout the experiment (30 days). Following 7 days of HFD feeding, streptozotocin was administered (150 mg/kg, intraperitoneal) to induce diabetes. From day 11 to 30, diabetic mice received either curcumin (100 or 200 mg/kg/day, oral), CB2R antagonist AM630 (1 mg/kg/day, intraperitoneal) or both, with concurrent isoproterenol (150 mg/kg, subcutaneous) administration on day 28 and 29. Diabetic mice with myocardial infarction showed an altered hemodynamic pattern and lipid profile, reduced injury markers, antioxidants with increased lipid peroxidation in the myocardium, and elevated glucose and liver enzymes in the blood. Moreover, an increased pro-inflammatory markers, histological severity, myonecrosis, and edema were observed. Curcumin compensated for hemodynamic fluctuations, restored biochemical markers, preserved antioxidant capacity, decreased cytokines levels, and restored cardiac functionality. However, the AM630 pre-treatment attenuated the effects of curcumin. The data suggest the involvement of CB2R in the actions of curcumin such as in the prevention of myocardial stress and in the improvement of the normal status of the myocardial membrane associated with diabetes. Full article
(This article belongs to the Section Physiology and Pathology)
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16 pages, 4202 KiB  
Article
Dysregulation of the Amniotic PPARγ Pathway by Phthalates: Modulation of the Anti-Inflammatory Activity of PPARγ in Human Fetal Membranes
by Audrey Antoine, Coraline De Sousa Do Outeiro, Coline Charnay, Corinne Belville, Fanny Henrioux, Denis Gallot, Loïc Blanchon, Régine Minet-Quinard and Vincent Sapin
Life 2022, 12(4), 544; https://doi.org/10.3390/life12040544 - 6 Apr 2022
Cited by 1 | Viewed by 1990
Abstract
Phthalates are reprotoxic pollutants that are omnipresent in the environment. Detectable in amniotic fluid, these compounds (with the most concentrated being mono-2-ethylhexyl phthalate (MEHP)) are in direct contact with fetal membranes (FMs). They can lead to the premature rupture of FMs by deregulating [...] Read more.
Phthalates are reprotoxic pollutants that are omnipresent in the environment. Detectable in amniotic fluid, these compounds (with the most concentrated being mono-2-ethylhexyl phthalate (MEHP)) are in direct contact with fetal membranes (FMs). They can lead to the premature rupture of FMs by deregulating cellular and molecular pathways, such as, for example, the nuclear transcription factor peroxysome proliferator-activated receptor gamma (PPARγ) pathway. The objective was to study the impact of MEHP on the PPARγ pathway in FMs using amnion and choriodecidua across the three trimesters of pregnancy and the amniotic epithelial AV3 cell model by analyzing (i) PPARγ expression (mRNA and proteins) using RT-qPCR and Western blot assays; (ii) cytotoxicity and cell viability following MEHP treatment by lactate dehydrogenase (LDH) measurement and using Cell-counting Kit 8; and (iii) modulation by MEHP of PPARγ transcriptional activity (using a reporter gene assay) and PPARγ anti-inflammatory properties (by measuring IL6 and IL8 levels). PPARγ is expressed in the human amnion and choriodecidua during the three trimesters of pregnancy and in amniotic cells. In the AV3 cell line, MEHP is not cytotoxic and does not reduce cell viability, but it reduces PPARγ activity, here induced by a classical agonist without influencing its expression. MEHP also reduces PPARγ’s anti-inflammatory properties. In conclusion, PPARγ signaling is dysregulated by MEHP; this paves the way for future explorations to highlight the hypothesis of phthalates as an amniotic PPARγ disruptor that can explain the premature rupture of FMs. 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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15 pages, 1168 KiB  
Article
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 2491
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  
Article
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 1 | Viewed by 2298
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  
Article
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 6 | Viewed by 2349
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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17 pages, 8142 KiB  
Article
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 2253
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  
Communication
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 4285
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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13 pages, 2168 KiB  
Article
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 2943
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  
Article
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 Grandisadd Show full author list remove Hide full author list
Life 2022, 12(3), 402; https://doi.org/10.3390/life12030402 - 10 Mar 2022
Cited by 7 | Viewed by 3068
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  
Article
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 2344
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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14 pages, 1085 KiB  
Article
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 2343
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  
Article
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 11 | Viewed by 4755
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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12 pages, 3958 KiB  
Article
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 2902
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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12 pages, 1814 KiB  
Article
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 2930
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  
Article
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 2299
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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11 pages, 589 KiB  
Article
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 16 | Viewed by 3333
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  
Article
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 3671
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  
Article
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 3185
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 Dmax 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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14 pages, 2052 KiB  
Article
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 3360
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  
Article
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 4592
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  
Article
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 4951
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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51 pages, 1098 KiB  
Article
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 6118
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  
Article
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 2136
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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16 pages, 1104 KiB  
Article
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 6 | Viewed by 6968
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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12 pages, 5917 KiB  
Article
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 3004
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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11 pages, 893 KiB  
Article
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 5 | Viewed by 4102
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  
Article
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 3322
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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17 pages, 2648 KiB  
Article
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 3994
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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15 pages, 2432 KiB  
Article
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 5 | Viewed by 2755
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  
Article
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 Pedicelliadd Show full author list remove Hide full author list
Life 2021, 11(12), 1423; https://doi.org/10.3390/life11121423 - 17 Dec 2021
Cited by 18 | Viewed by 3098
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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21 pages, 3488 KiB  
Article
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 3264
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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18 pages, 2890 KiB  
Article
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 2714
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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