Life | August 2021 - Browse Articles

28 pages, 5406 KiB

Open AccessArticle

Arf GTPases Are Required for the Establishment of the Pre-Assembly Compartment in the Early Phase of Cytomegalovirus Infection

by Valentino Pavišić, Hana Mahmutefendić Lučin, Gordana Blagojević Zagorac and Pero Lučin

Life 2021, 11(8), 867; https://doi.org/10.3390/life11080867 - 23 Aug 2021

Cited by 6 | Viewed by 2992

Abstract

Shortly after entering the cells, cytomegaloviruses (CMVs) initiate massive reorganization of cellular endocytic and secretory pathways, which results in the forming of the cytoplasmic virion assembly compartment (AC). We have previously shown that the formation of AC in murine CMV- (MCMV) infected cells [...] Read more.

Shortly after entering the cells, cytomegaloviruses (CMVs) initiate massive reorganization of cellular endocytic and secretory pathways, which results in the forming of the cytoplasmic virion assembly compartment (AC). We have previously shown that the formation of AC in murine CMV- (MCMV) infected cells begins in the early phase of infection (at 4–6 hpi) with the pre-AC establishment. Pre-AC comprises membranes derived from the endosomal recycling compartment, early endosomes, and the trans-Golgi network, which is surrounded by fragmented Golgi cisterns. To explore the importance of Arf GTPases in the biogenesis of the pre-AC, we infected Balb 3T3 cells with MCMV and analyzed the expression and intracellular localization of Arf proteins in the early phases (up to 16 hpi) of infection and the development of pre-AC in cells with a knockdown of Arf protein expression by small interfering RNAs (siRNAs). Herein, we show that even in the early phase, MCMVs cause massive reorganization of the Arf system of the host cells and induce the over-recruitment of Arf proteins onto the membranes of pre-AC. Knockdown of Arf1, Arf3, Arf4, or Arf6 impaired the establishment of pre-AC. However, the knockdown of Arf1 and Arf6 also abolished the establishment of infection. Our study demonstrates that Arf GTPases are required for different steps of early cytomegalovirus infection, including the establishment of the pre-AC. Full article

(This article belongs to the Special Issue Biology of Cytomegalovirus Infection)

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12 pages, 1075 KiB

Open AccessArticle

Identification of Targeted Proteins by Jamu Formulas for Different Efficacies Using Machine Learning Approach

by Sony Hartono Wijaya, Farit Mochamad Afendi, Irmanida Batubara, Ming Huang, Naoaki Ono, Shigehiko Kanaya and Md. Altaf-Ul-Amin

Life 2021, 11(8), 866; https://doi.org/10.3390/life11080866 - 23 Aug 2021

Cited by 4 | Viewed by 2791

Abstract

Background: We performed in silico prediction of the interactions between compounds of Jamu herbs and human proteins by utilizing data-intensive science and machine learning methods. Verifying the proteins that are targeted by compounds of natural herbs will be helpful to select natural herb-based [...] Read more.

Background: We performed in silico prediction of the interactions between compounds of Jamu herbs and human proteins by utilizing data-intensive science and machine learning methods. Verifying the proteins that are targeted by compounds of natural herbs will be helpful to select natural herb-based drug candidates. Methods: Initially, data related to compounds, target proteins, and interactions between them were collected from open access databases. Compounds are represented by molecular fingerprints, whereas amino acid sequences are represented by numerical protein descriptors. Then, prediction models that predict the interactions between compounds and target proteins were constructed using support vector machine and random forest. Results: A random forest model constructed based on MACCS fingerprint and amino acid composition obtained the highest accuracy. We used the best model to predict target proteins for 94 important Jamu compounds and assessed the results by supporting evidence from published literature and other sources. There are 27 compounds that can be validated by professional doctors, and those compounds belong to seven efficacy groups. Conclusion: By comparing the efficacy of predicted compounds and the relations of the targeted proteins with diseases, we found that some compounds might be considered as drug candidates. Full article

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

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15 pages, 6579 KiB

Open AccessArticle

Identification of Compound CB-2 as a Novel Late-Stage Autophagy Inhibitor Exhibits Inhibitory Potency against A549 Cells

by Zhihui Liu, Lu Zhang, Yachao Liu, Hanxiao Zhang, Jingxuan Chen, Gaoqing Feng, Peichang Yang, Fangfang Sha, Liuqing Cui and Gangchun Sun

Life 2021, 11(8), 865; https://doi.org/10.3390/life11080865 - 23 Aug 2021

Cited by 3 | Viewed by 2391

Abstract

Autophagy has been recognized as a stress tolerance mechanism that maintains cell viability, which contributes to tumor progression, dormancy, and treatment resistance. The inhibition of autophagy in cancer has the potential to improve the therapeutic efficacy. It is therefore of great significance to [...] Read more.

Autophagy has been recognized as a stress tolerance mechanism that maintains cell viability, which contributes to tumor progression, dormancy, and treatment resistance. The inhibition of autophagy in cancer has the potential to improve the therapeutic efficacy. It is therefore of great significance to search for new autophagy inhibitors. In the present study, after screening a series of curcumin derivatives synthesized in our laboratory, (E)-3-((E)-4-chlorobenzylidene)-5-((5-methoxy-1H-indol-3-yl)methylene)-1-methylpiperidin-4-one (CB-2) was selected as a candidate for further study. We found that CB-2 increased the LC3B-II and SQSTM1 levels associated with the accumulation of autophagosomes in non-small cell lung cancer (NSCLC) A549 cells. The increased level of LC3B-II induced by CB-2 was neither eliminated when autophagy initiation was suppressed by wortmannin nor further increased when autophagosome degradation was inhibited by chloroquine (CQ). CB-2 enhanced the accumulation of LC3B-II under starvation conditions. Further studies revealed that CB-2 did not affect the levels of the key proteins involved in autophagy induction but significantly blocked the fusion of autophagosomes with lysosomes. High-dose CB-2 induced the apoptosis and necrosis of A549 cells, while a lower dose of CB-2 mainly impaired the migrative capacity of A549 cells, which only slightly induced cell apoptosis. CB-2 increased the levels of mitochondrial-derived reactive oxygen species (ROS) while decreasing the mitochondrial membrane potential (MMP). Scavenging ROS via N-acetylcysteine (NAC) reversed CB-2-induced autophagy inhibition and its inhibitory effect against A549 cells. In conclusion, CB-2 serves as a new late-stage autophagy inhibitor, which has a strong inhibitory potency against A549 cells. Full article

(This article belongs to the Special Issue Autophagy and Cancer 2021)

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13 pages, 2765 KiB

Open AccessSystematic Review

Repurposing Colchicine in Treating Patients with COVID-19: A Systematic Review and Meta-Analysis

by Chi-Hone Lien, Ming-Dar Lee, Shun-Long Weng, Chao-Hsu Lin, Lawrence Yu-Min Liu, Yu-Lin Tai, Wei-Te Lei, Jui-Ming Liu, Ya-Ning Huang, Hsin Chi, Nan-Chang Chiu and Chien-Yu Lin

Life 2021, 11(8), 864; https://doi.org/10.3390/life11080864 - 23 Aug 2021

Cited by 21 | Viewed by 4594

Abstract

Coronavirus disease 2019 (COVID-19) had caused huge health losses worldwide. Several drugs had been applied to treat patients with COVID-19, and repurposing colchicine had been proposed for its anti-inflammatory properties via several pathways. In this systematic review, we evaluated the effects of colchicine [...] Read more.

Coronavirus disease 2019 (COVID-19) had caused huge health losses worldwide. Several drugs had been applied to treat patients with COVID-19, and repurposing colchicine had been proposed for its anti-inflammatory properties via several pathways. In this systematic review, we evaluated the effects of colchicine treatment. From inception to May 31, 2021, databases, including PubMed, EMbase, medRxiv, and Research Square were searched, and 11 studies were enrolled. A total of 17,205 COVID-19 patients with male predominance (62.9%) were analyzed. Patients with colchicine treatment had a significantly lower risk of mortality (odds ratio (OR): 0.57, 95% confidence interval (CI): 0.38–0.87, I²: 72%; p < 0.01) and a non-significantly lower rate of mechanical ventilation (OR: 0.67, 95%CI: 0.39–1.15). The side effects were mild and not significantly different (OR: 2.03, 95%CI: 0.51–8.09). Subgroup analysis with randomized controlled trials showed no statistically significant difference in the mortality (OR: 0.80, 95%CI: 0.44–1.46, I²: 33%; p = 0.22). In conclusion, our meta-analysis found that colchicine treatment was associated with a significantly lower risk of mortality in patients with COVID-19. However, this benefit was not observed in the subgroup analysis of randomized controlled trials. Further randomized controlled studies are required to confirm the potential benefits of colchicine treatment. Full article

(This article belongs to the Topic Burden of COVID-19 in Different Countries)

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14 pages, 4695 KiB

Open AccessArticle

Enhanced Expression of Thaumatin-like Protein Gene (LeTLP1) Endows Resistance to Trichoderma atroviride in Lentinula edodes

by Xiaolong Ma, Xiaolin Fan, Gangzheng Wang, Ruiping Xu, Lianlian Yan, Yan Zhou, Yuhua Gong, Yang Xiao and Yinbing Bian

Life 2021, 11(8), 863; https://doi.org/10.3390/life11080863 - 23 Aug 2021

Cited by 16 | Viewed by 3484

Abstract

Lentinula edodes (shiitake mushrooms) is heavily affected by the infection of Trichoderma atroviride, causing yield loss and decreases quality in shiitake mushrooms. The selection and breeding of fungal-resistant L. edodes species are an important approach to protecting L. edodes from T. atroviride [...] Read more.

Lentinula edodes (shiitake mushrooms) is heavily affected by the infection of Trichoderma atroviride, causing yield loss and decreases quality in shiitake mushrooms. The selection and breeding of fungal-resistant L. edodes species are an important approach to protecting L. edodes from T. atroviride infection. Herein, a highly resistant L. edodes strain (Y3334) and a susceptible strain (Y55) were obtained by using a resistance evaluation test. Transcriptome analyses and qRT-PCR detection showed that the expression level of LeTLP1 (LE01Gene05009) was strongly induced in response to T. atroviride infection in the resistant Y3334. Then, LeTLP1-silenced and LeTLP1-overexpression transformants were obtained. Overexpression of LeTLP1 resulted in resistance to T. atroviride. Compared with the parent strain Y3334, LeTLP1-silenced transformants had reduced resistance relative to T. atroviride. Additionally, the LeTLP1 protein (Y3334) exhibited significant antifungal activity against T. atroviride. These findings suggest that overexpression of LeTLP1 is a major mechanism for the resistance of L. edodes to T. atroviride. The molecular basis provides a theoretical basis for the breeding of resistant L. edodes strains and can eventually contribute to the mushroom cultivation industry and human health. Full article

(This article belongs to the Section Microbiology)

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20 pages, 2861 KiB

Open AccessBrief Report

Comparative Analysis of PacBio and Oxford Nanopore Sequencing Technologies for Transcriptomic Landscape Identification of Penaeus monodon

by Zulema Udaondo, Kanchana Sittikankaew, Tanaporn Uengwetwanit, Thidathip Wongsurawat, Chutima Sonthirod, Piroon Jenjaroenpun, Wirulda Pootakham, Nitsara Karoonuthaisiri and Intawat Nookaew

Life 2021, 11(8), 862; https://doi.org/10.3390/life11080862 - 23 Aug 2021

Cited by 13 | Viewed by 8385

Abstract

With the advantages that long-read sequencing platforms such as Pacific Biosciences (Menlo Park, CA, USA) (PacBio) and Oxford Nanopore Technologies (Oxford, UK) (ONT) can offer, various research fields such as genomics and transcriptomics can exploit their benefits. Selecting an appropriate sequencing platform is [...] Read more.

With the advantages that long-read sequencing platforms such as Pacific Biosciences (Menlo Park, CA, USA) (PacBio) and Oxford Nanopore Technologies (Oxford, UK) (ONT) can offer, various research fields such as genomics and transcriptomics can exploit their benefits. Selecting an appropriate sequencing platform is undoubtedly crucial for the success of the research outcome, thus there is a need to compare these long-read sequencing platforms and evaluate them for specific research questions. This study aims to compare the performance of PacBio and ONT platforms for transcriptomic analysis by utilizing transcriptome data from three different tissues (hepatopancreas, intestine, and gonads) of the juvenile black tiger shrimp, Penaeus monodon. We compared three important features: (i) main characteristics of the sequencing libraries and their alignment with the reference genome, (ii) transcript assembly features and isoform identification, and (iii) correlation of the quantification of gene expression levels for both platforms. Our analyses suggest that read-length bias and differences in sequencing throughput are highly influential factors when using long reads in transcriptome studies. These comparisons can provide a guideline when designing a transcriptome study utilizing these two long-read sequencing technologies. Full article

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

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14 pages, 1587 KiB

Open AccessArticle

Analysis of Homozygous-by-Descent (HBD) Segments for Purebred and Crossbred Pigs in Russia

by Siroj Bakoev, Anatoly Kolosov, Faridun Bakoev, Olga Kostyunina, Nekruz Bakoev, Timofey Romanets, Olga Koshkina and Lyubov Getmantseva

Life 2021, 11(8), 861; https://doi.org/10.3390/life11080861 - 22 Aug 2021

Cited by 6 | Viewed by 2394

Abstract

Intensive selection raises the efficiency of pig farming considerably, but it also promotes the accumulation of homozygosity, which can lead to an increase in inbreeding and the accumulation of deleterious variation. The analysis of segments homozygous-by-descent (HBD) and non-HBD segments in purebred and [...] Read more.

Intensive selection raises the efficiency of pig farming considerably, but it also promotes the accumulation of homozygosity, which can lead to an increase in inbreeding and the accumulation of deleterious variation. The analysis of segments homozygous-by-descent (HBD) and non-HBD segments in purebred and crossbred pigs is of great interest. Research was carried out on 657 pigs, of which there were Large White (LW, n = 280), Landrace (LR, n = 218) and F1 female (♂LR × ♀LW) (F1, n = 159). Genotyping was performed using the GeneSeek^® GGP Porcine HD Genomic Profiler v1 (Illumina Inc., USA). To identify HBD segments and estimate autozygosity (inbreeding coefficient), we used the multiple HBD classes model. LW pigs exhibited 50,420 HBD segments, an average of 180 per animal; LR pigs exhibited 33,586 HBD segments, an average of 154 per animal; F1 pigs exhibited 21,068 HBD segments, an average of 132 per animal. The longest HBD segments in LW were presented in SSC1, SSC13 and SSC15; in LR, in SSC1; and in F1, in SSC15. In these segments, 3898 SNPs localized in 1252 genes were identified. These areas overlap with 441 QTLs (SSC1—238 QTLs; SSC13—101 QTLs; and SSC15—102 QTLs), including 174 QTLs for meat and carcass traits (84 QTLs—fatness), 127 QTLs for reproduction traits (100 QTLs—litter traits), 101 for production traits (69 QTLs—growth and 30 QTLs—feed intake), 21 QTLs for exterior traits (9 QTLs—conformation) and 18 QTLs for health traits (13 QTLs—blood parameters). Thirty SNPs were missense variants. Whilst estimating the potential for deleterious variation, six SNPs localized in the NEDD4, SEC11C, DCP1A, CCT8, PKP4 and TENM3 genes were identified, which may show deleterious variation. A high frequency of potential deleterious variation was noted for LR in DCP1A, and for LW in TENM3 and PKP4. In all cases, the genotype frequencies in F1 were intermediate between LR and LW. The findings presented in our work show the promise of genome scanning for HBD as a strategy for studying population history, identifying genomic regions and genes associated with important economic traits, as well as deleterious variation. Full article

(This article belongs to the Special Issue Life: Computational Genomics)

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9 pages, 248 KiB

Open AccessArticle

Metabolic Changes in SARS-CoV-2 Infection: Clinical Data and Molecular Hypothesis to Explain Alterations of Lipid Profile and Thyroid Function Observed in COVID-19 Patients

by Damiano D’Ardes, Ilaria Rossi, Benedetta Bucciarelli, Marco Allegra, Francesco Bianco, Bruna Sinjari, Michele Marchioni, Marta Di Nicola, Francesca Santilli, Maria Teresa Guagnano, Francesco Cipollone and Marco Bucci

Life 2021, 11(8), 860; https://doi.org/10.3390/life11080860 - 22 Aug 2021

Cited by 9 | Viewed by 2992

Abstract

It seems that during SARS-CoV-2 infection, total cholesterol, LDL-C, and HDL-C values decrease and lipids could play a fundamental role in viral replication. Moreover, it has been shown that SARS-CoV-2 infection could influence thyroid function. We performed a retrospective analysis of 118 hospitalized [...] Read more.

It seems that during SARS-CoV-2 infection, total cholesterol, LDL-C, and HDL-C values decrease and lipids could play a fundamental role in viral replication. Moreover, it has been shown that SARS-CoV-2 infection could influence thyroid function. We performed a retrospective analysis of 118 hospitalized patients with COVID-19, comparing pre-infection lipid profile (53 patients) and thyroid-stimulating hormone (TSH) values (45 patients) to those measured on admission. Our aim was to evaluate whether SARS-CoV-2 infection could be involved in thyroid and lipid profile alterations and study possible correlations with disease severity and clinical outcome. Median baseline values at the admission time were: total cholesterol at 136.89 ± 42.73 mg/dL, LDL-C 81.53 ± 30.35 mg/dL, and HDL-C 32.36 ± 15.13 mg/dL; and triglycerides at 115.00 ± 40.45 mg/dL, non-HDL-C 104.53 ± 32.63 md/dL, and TSH 1.15 ± 1.08 μUI/mL. Median values of pre-infection total cholesterol, HDL-C, and TSH were significantly higher than those measured at the admission time (p value < 0.05). The C-reactive protein (CRP) negatively correlated with LDL-C (p = 0.013) and HDL-C (p = 0.05). Our data underline a possible impact of SARS-CoV-2 infection on thyroid function. Moreover it suggests a possible relation between COVID-19 and the lipid profile with a negative correlation between CRP, LDL-C, and HDL-C values, proposing the hypothesis that lipid lowering could follow the rising of the COVID-19 inflammatory state. Full article

(This article belongs to the Collection COVID-19 and Life)

27 pages, 53006 KiB

Open AccessArticle

Endosomal Phosphatidylinositol-3-Phosphate-Associated Functions Are Dispensable for Establishment of the Cytomegalovirus Pre-Assembly Compartment but Essential for the Virus Growth

by Marina Marcelić, Hana Mahmutefendić Lučin, Antonija Jurak Begonja, Gordana Blagojević Zagorac, Vanda Juranić Lisnić and Pero Lučin

Life 2021, 11(8), 859; https://doi.org/10.3390/life11080859 - 22 Aug 2021

Cited by 4 | Viewed by 2971

Abstract

Murine cytomegalovirus (MCMV) initiates the stepwise establishment of the pre-assembly compartment (pre-AC) in the early phase of infection by the expansion of the early endosome (EE)/endosomal recycling compartment (ERC) interface and relocation of the Golgi complex. We depleted Vps34-derived phosphatidylinositol-3-phosphate (PI(3)P) at EEs [...] Read more.

Murine cytomegalovirus (MCMV) initiates the stepwise establishment of the pre-assembly compartment (pre-AC) in the early phase of infection by the expansion of the early endosome (EE)/endosomal recycling compartment (ERC) interface and relocation of the Golgi complex. We depleted Vps34-derived phosphatidylinositol-3-phosphate (PI(3)P) at EEs by VPS34-IN1 and inhibited PI(3)P-associated functions by overexpression of 2xFYVE- and p40PX PI(3)P-binding modules to assess the role of PI(3)P-dependent EE domains in the pre-AC biogenesis. We monitored the accumulation of Rab10 and Evectin-2 in the inner pre-AC and the relocation of GM130-positive cis-Golgi organelles to the outer pre-AC by confocal microscopy. Although PI(3)P- and Vps34-positive endosomes build a substantial part of pre-AC, the PI(3)P depletion and the inhibition of PI(3)P-associated functions did not prevent the establishment of infection and progression through the early phase. The PI(3)P depletion in uninfected and MCMV-infected cells rapidly dispersed PI(3)P-bond proteins and reorganized EEs, including ablation of EE-to-ERC transport and relocation of Rab11 endosomes. The PI(3)P depletion one hour before pre-AC initiation and overexpression of 2xFYVE and p40PX domains neither prevented Rab10- and Evectin-2 accumulation, nor Golgi unlinking and relocation. These data demonstrate that PI(3)P-dependent functions, including the Rab11-dependent EE-to-ERC route, are dispensable for pre-AC initiation. Nevertheless, the virus growth was drastically reduced in PI(3)P-depleted cells, indicating that PI(3)P-associated functions are essential for the late phase of infection. Full article

(This article belongs to the Special Issue Biology of Cytomegalovirus Infection)

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12 pages, 2672 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 9 | Viewed by 2758

Abstract

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

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

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

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12 pages, 1188 KiB

Open AccessEditor’s ChoiceReview

Horizontal Gene Transfers in Plants

by Emilie Aubin, Moaine El Baidouri and Olivier Panaud

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

Cited by 18 | Viewed by 6631

Abstract

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

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

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

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20 pages, 4007 KiB

Open AccessArticle

The Performance of HepG2 and HepaRG Systems through the Glass of Acetaminophen-Induced Toxicity

by Tamás Lőrincz, Veronika Deák, Kinga Makk-Merczel, Dóra Varga, Péter Hajdinák and András Szarka

Life 2021, 11(8), 856; https://doi.org/10.3390/life11080856 - 21 Aug 2021

Cited by 14 | Viewed by 4443

Abstract

Investigation of drug-induced liver injuries requires appropriate in vivo and in vitro toxicological model systems. In our study, an attempt was made to compare the hepatocarcinoma HepG2 and the stem cell-derived HepaRG cell lines both in two- and three-dimensional culture conditions to find [...] Read more.

Investigation of drug-induced liver injuries requires appropriate in vivo and in vitro toxicological model systems. In our study, an attempt was made to compare the hepatocarcinoma HepG2 and the stem cell-derived HepaRG cell lines both in two- and three-dimensional culture conditions to find the most suitable model. Comparison of the liver-specific characteristics of these models was performed via the extent and mechanism of acetaminophen (APAP)-induced hepatotoxicity. Investigating the detailed mechanism of APAP-induced hepatotoxicity, different specific cell death inhibitors were used: the pan-caspase inhibitor zVAD-fmk and dabrafenib significantly protected both cell lines from APAP-induced cell death. However, the known specific inhibitors of necroptosis (necrostatin-1 and MDIVI) were only effective in differentiated HepaRG, which suggest a differential execution of activated pathways in the two models. By applying 3D culture methods, CYP2E1 mRNA levels could be elevated, but we failed to achieve a significant increase in hepatocyte function; hence, the 3D cultivation especially in APAP toxicity studies is not necessarily worth the complicated maintenance. Based on our findings, the hepatocyte functions of HepaRG may stand between the properties of HepG2 cells and primary hepatocytes (PHHs). However, it should be noted that in contrast to PHHs having many limitations, HepaRG cells are relatively immortal, having a stable phenotype and CYP450 expression. Full article

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

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12 pages, 526 KiB

Open AccessReview

The Role of Gut Microbiota in Aging and Aging Related Neurodegenerative Disorders: Insights from Drosophila Model

by Yan Kong, Liyuan Wang and Baichun Jiang

Life 2021, 11(8), 855; https://doi.org/10.3390/life11080855 - 20 Aug 2021

Cited by 11 | Viewed by 4438

Abstract

Aging is characterized by a time dependent impairment of physiological function and increased susceptibility to death. It is the major risk factor for neurodegeneration. Neurodegenerative disorders including Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the main causes of dementia in the old [...] Read more.

Aging is characterized by a time dependent impairment of physiological function and increased susceptibility to death. It is the major risk factor for neurodegeneration. Neurodegenerative disorders including Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the main causes of dementia in the old population. Gut microbiota is a community of microorganisms colonized in the gastrointestinal (GI) tract. The alteration of gut microbiota has been proved to be associated with aging and aging related neurodegeneration. Drosophila is a powerful tool to study microbiota-mediated physiological and pathological functions. Here, we summarize the recent advances using Drosophila as model organisms to clarify the molecular mechanisms and develop a therapeutic method targeting microbiota in aging and aging-related neurodegenerative disorders. Full article

(This article belongs to the Special Issue The Microbiota-Gut-Brain Axis in Neurodegenerative Diseases)

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10 pages, 966 KiB

Open AccessArticle

Is Preterm Birth a Risk Factor for Subsequent Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder in Children with Febrile Seizure?—A Retrospective Study

by Chien-Heng Lin, Wei-De Lin, I-Ching Chou, Inn-Chi Lee and Syuan-Yu Hong

Life 2021, 11(8), 854; https://doi.org/10.3390/life11080854 - 20 Aug 2021

Cited by 3 | Viewed by 2889

Abstract

Febrile seizure (FS) is the most prevalent childhood seizure; it is significantly related to subsequent epilepsy and has possible links to childhood neurodevelopmental disorders. Separately, premature births are believed to increase the risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder [...] Read more.

Febrile seizure (FS) is the most prevalent childhood seizure; it is significantly related to subsequent epilepsy and has possible links to childhood neurodevelopmental disorders. Separately, premature births are believed to increase the risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Therefore, this study investigated whether preterm birth is a risk factor for subsequent epilepsy, ASD, and ADHD in children with FS. We retrospectively collected data for children aged < 5 years with FS from 1 January 2005, to 31 December 2013. We divided these children into two groups—the premature birth group and the full-term group—and compared their incidence rates of epilepsy, ASD and ADHD. The data of 426 patients with history of febrile convulsion were retrospectively collected. The premature birth group (FS+/preterm+) had 108 patients and the full-term group (FS+/preterm−) had 318 patients. The overall epilepsy risk in the FS+/preterm+ group was higher than in the FS+/preterm− group (odds ratio [OR], 2.52; 95% confidence interval [CI], 1.14–5.58; p = 0.02). The overall risk of ADHD in the FS+/preterm+ group was higher than that in the FS+/preterm− group (OR, 6.41; 95% CI, 3.39–12.09; p = 0.0001). In addition, children with FS+/preterm+ had 16.9 times (95% CI, 4.79–59.7; p = 0.0001) higher odds of having ASD compared with those with FS+/preterm−. Preterm birth may be a risk factor for subsequent epilepsy, ASD and ADHD in children with FS. Full article

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

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19 pages, 1366 KiB

Open AccessReview

Post-Transcriptional Control in the Regulation of Polyhydroxyalkanoates Synthesis

by Alexandra Peregrina, João Martins-Lourenço, Filomena Freitas, Maria A. M. Reis and Cecília M. Arraiano

Life 2021, 11(8), 853; https://doi.org/10.3390/life11080853 - 20 Aug 2021

Cited by 4 | Viewed by 3766

Abstract

The large production of non-degradable petrol-based plastics has become a major global issue due to its environmental pollution. Biopolymers produced by microorganisms such as polyhydroxyalkanoates (PHAs) are gaining potential as a sustainable alternative, but the high cost associated with their industrial production has [...] Read more.

The large production of non-degradable petrol-based plastics has become a major global issue due to its environmental pollution. Biopolymers produced by microorganisms such as polyhydroxyalkanoates (PHAs) are gaining potential as a sustainable alternative, but the high cost associated with their industrial production has been a limiting factor. Post-transcriptional regulation is a key step to control gene expression in changing environments and has been reported to play a major role in numerous cellular processes. However, limited reports are available concerning the regulation of PHA accumulation in bacteria, and many essential regulatory factors still need to be identified. Here, we review studies where the synthesis of PHA has been reported to be regulated at the post-transcriptional level, and we analyze the RNA-mediated networks involved. Finally, we discuss the forthcoming research on riboregulation, synthetic, and metabolic engineering which could lead to improved strategies for PHAs synthesis in industrial production, thereby reducing the costs currently associated with this procedure. Full article

(This article belongs to the Special Issue Microbial Biopolymers: From Synthesis to Properties and Applications)

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17 pages, 11973 KiB

Open AccessArticle

Spatial and Species Variations of Bacterial Community Structure and Putative Function in Seagrass Rhizosphere Sediment

by Juan Ling, Weiguo Zhou, Qingsong Yang, Jianping Yin, Jian Zhang, Qiuying Peng, Xiaofang Huang, Yuhang Zhang and Junde Dong

Life 2021, 11(8), 852; https://doi.org/10.3390/life11080852 - 20 Aug 2021

Cited by 6 | Viewed by 3923

Abstract

Seagrasses are an important part of the coral reef ecosystem, and their rhizosphere microbes are of great ecological importance. However, variations in diversity, composition, and potential functions of bacterial communities in the seagrass rhizosphere of coral reef ecosystems remain unclear. This study employed [...] Read more.

Seagrasses are an important part of the coral reef ecosystem, and their rhizosphere microbes are of great ecological importance. However, variations in diversity, composition, and potential functions of bacterial communities in the seagrass rhizosphere of coral reef ecosystems remain unclear. This study employed the high-throughput sequencing based on 16S rDNA gene sequences and functional annotation of prokaryotic taxa (FAPROTAX) analysis to investigate these variations based on seagrass species and sampling locations, respectively. Results demonstrated that the seagrass rhizosphere microbial community was mainly dominated by phylum Proteobacteria (33.47%), Bacteroidetes (23.33%), and Planctomycetes (12.47%), while functional groups were mainly composed of sulfate respiration (14.09%), respiration of sulfur compounds (14.24%), aerobic chemoheterotrophy (20.87%), and chemoheterotrophy (26.85%). Significant differences were evident in alpha diversity, taxonomical composition and putative functional groups based on seagrass species and sampling locations. Moreover, the core microbial community of all investigated samples was identified, accounting for 63.22% of all obtained sequences. Network analysis indicated that most microbes had a positive correlation (82.41%), and two module hubs (phylum Proteobacteria) were investigated. Furthermore, a significant positive correlation was found between the OTUs numbers obtained and the functional groups assigned for seagrass rhizosphere microbial communities (p < 0.01). Our result would facilitate future investigation of the function of seagrass rhizosphere microbes. Full article

(This article belongs to the Section Animal Science)

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12 pages, 2368 KiB

Open AccessArticle

Sphingosine-1-Phosphate Induces ATP Release via Volume-Regulated Anion Channels in Breast Cell Lines

by Kishio Furuya, Hiroaki Hirata, Takeshi Kobayashi and Masahiro Sokabe

Life 2021, 11(8), 851; https://doi.org/10.3390/life11080851 - 19 Aug 2021

Cited by 5 | Viewed by 3356

Abstract

High interstitial level of ATP and its lysate adenosine in the cancer microenvironment are considered a halo mark of cancer. Adenosine acts as a strong immune suppressor. However, the source of ATP release is unclear. We clarified the release of ATP via volume-regulated [...] Read more.

High interstitial level of ATP and its lysate adenosine in the cancer microenvironment are considered a halo mark of cancer. Adenosine acts as a strong immune suppressor. However, the source of ATP release is unclear. We clarified the release of ATP via volume-regulated anion channels (VRACs) in breast cell lines using an ATP luminescence imaging system. We detected a slowly rising diffuse pattern of ATP release that was only observed in undifferentiated cells, not in differentiated primary cultured cells. This was confirmed by suppression with DCPIB, a blocker of VRACs, and shRNA for LRRC8A, an indispensable subunit of VRACs. We herein demonstrated that the inflammatory mediator sphingosine-1-phosphate (S1P), which exists abundantly in the cancer microenvironment, induced a diffuse pattern of ATP release isovolumetrically. The response was dose-dependent and suppressed by the knock-down of LRRC8A. It was also suppressed by blockers of S1P receptor 1 and 2 (W146 and JTE013, respectively). RTqPCR demonstrated the prominent presence of S1PR1 and S1PR2 mRNAs. We discussed the roles of S1P-induced ATP release in the cancer microenvironment. Full article

(This article belongs to the Topic ATP Release in Health and Disease)

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15 pages, 1822 KiB

Open AccessReview

Implicit Memory and Anesthesia: A Systematic Review and Meta-Analysis

by Federico Linassi, David Peter Obert, Eleonora Maran, Paola Tellaroli, Matthias Kreuzer, Robert David Sanders and Michele Carron

Life 2021, 11(8), 850; https://doi.org/10.3390/life11080850 - 19 Aug 2021

Cited by 5 | Viewed by 3768

Abstract

General anesthesia should induce unconsciousness and provide amnesia. Amnesia refers to the absence of explicit and implicit memories. Unlike explicit memory, implicit memory is not consciously recalled, and it can affect behavior/performance at a later time. The impact of general anesthesia in preventing [...] Read more.

General anesthesia should induce unconsciousness and provide amnesia. Amnesia refers to the absence of explicit and implicit memories. Unlike explicit memory, implicit memory is not consciously recalled, and it can affect behavior/performance at a later time. The impact of general anesthesia in preventing implicit memory formation is not well-established. We performed a systematic review with meta-analysis of studies reporting implicit memory occurrence in adult patients after deep sedation (Observer’s Assessment of Alertness/Sedation of 0–1 with spontaneous breathing) or general anesthesia. We also evaluated the impact of different anesthetic/analgesic regimens and the time point of auditory task delivery on implicit memory formation. The meta-analysis included the estimation of odds ratios (ORs) and 95% confidence intervals (CIs). We included a total of 61 studies with 3906 patients and 119 different cohorts. For 43 cohorts (36.1%), implicit memory events were reported. The American Society of Anesthesiologists (ASA) physical status III–IV was associated with a higher likelihood of implicit memory formation (OR:3.48; 95%CI:1.18–10.25, p < 0.05) than ASA physical status I–II. Further, there was a lower likelihood of implicit memory formation for deep sedation cases, compared to general anesthesia (OR:0.10; 95%CI:0.01–0.76, p < 0.05) and for patients receiving premedication with benzodiazepines compared to not premedicated patients before general anesthesia (OR:0.35; 95%CI:0.13–0.93, p = 0.05). Full article

(This article belongs to the Special Issue Frontiers in Anesthesia and Pain Medicine)

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14 pages, 3001 KiB

Open AccessArticle

Evaluating Ocular Response in the Retina and Optic Nerve Head after Single and Fractionated High-Energy Protons

by Xiao-Wen Mao, Seta Stanbouly, Tamako Jones and Gregory Nelson

Life 2021, 11(8), 849; https://doi.org/10.3390/life11080849 - 19 Aug 2021

Cited by 3 | Viewed by 2540

Abstract

There are serious concerns about possible late radiation damage to ocular tissue from prolonged space radiation exposure, and occupational and medical procedures. This study aimed to investigate the effects of whole-body high-energy proton exposure at a single dose on apoptosis, oxidative stress, and [...] Read more.

There are serious concerns about possible late radiation damage to ocular tissue from prolonged space radiation exposure, and occupational and medical procedures. This study aimed to investigate the effects of whole-body high-energy proton exposure at a single dose on apoptosis, oxidative stress, and blood-retina barrier (BRB) integrity in the retina and optic nerve head (ONH) region and to compare these radiation-induced effects with those produced by fractionated dose. Six-month-old C57BL/6 male mice were either sham irradiated or received whole-body high energy proton irradiation at an acute single dose of 0.5 Gy or 12 equal dose fractions for a total dose of 0.5 Gy over twenty-five days. At four months following irradiation, mice were euthanized and ocular tissues were collected for histochemical analysis. Significant increases in the number of apoptotic cells were documented in the mouse retinas and ONHs that received proton radiation with a single or fractionated dose (p < 0.05). Immunochemical analysis revealed enhanced immunoreactivity for oxidative biomarker, 4-hydroxynonenal (4-HNE) in the retina and ONH following single or fractionated protons with more pronounced changes observed with a single dose of 0.5 Gy. BRB integrity was also evaluated with biomarkers of aquaporin-4 (AQP-4), a water channel protein, a tight junction (TJ) protein, Zonula occludens-1 (ZO-1), and an adhesion molecule, the platelet endothelial cell adhesion molecule-1 (PECAM-1). A significantly increased expression of AQP-4 was observed in the retina following a single dose exposure compared to controls. There was also a significant increase in the expression of PECAM-1 and a decrease in the expression of ZO-1 in the retina. These changes give a strong indication of disturbance to BRB integrity in the retina. Interestingly, there was very limited immunoreactivity of AQP-4 and ZO-1 seen in the ONH region, pointing to possible lack of BRB properties as previously reported. Our data demonstrated that exposure to proton radiation of 0.5 Gy induced oxidative stress-associated apoptosis in the retina and ONH, and changes in BRB integrity in the retina. Our study also revealed the differences in BRB biomarker distribution between these two regions. In response to radiation insults, the cellular response in the retina and ONH may be differentially regulated in acute or hyperfractionated dose schedules. Full article

(This article belongs to the Special Issue Space Radiobiology)

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10 pages, 265 KiB

Open AccessArticle

The Association between Low Muscle Mass and Hepatic Steatosis in Asymptomatic Population in Korea

by Goh-Eun Chung, Hyo-Eun Park, Min-Joo Kim, Min-Sun Kwak, Jong-In Yang, Su-Jin Chung, Jeong-Yoon Yim and Ji-Won Yoon

Life 2021, 11(8), 848; https://doi.org/10.3390/life11080848 - 19 Aug 2021

Cited by 3 | Viewed by 1959

Abstract

Background: An association between low muscle mass and nonalcoholic fatty liver disease (NAFLD) has been suggested. We investigated this relationship using controlled attenuation parameter (CAP). Methods: A retrospective cohort of subjects had liver FibroScan^® (Echosens, Paris, France) and bioelectrical impedance analyses during [...] Read more.

Background: An association between low muscle mass and nonalcoholic fatty liver disease (NAFLD) has been suggested. We investigated this relationship using controlled attenuation parameter (CAP). Methods: A retrospective cohort of subjects had liver FibroScan^® (Echosens, Paris, France) and bioelectrical impedance analyses during health screening exams. Low muscle mass was defined based on appendicular skeletal muscle mass/body weight ratios of one (class I) or two (class II) standard deviations below the sex-specific mean for healthy young adults. Results: Among 960 subjects (58.1 years; 67.4% male), 344 (45.8%, class I) and 110 (11.5%, class II) had low muscle mass. After adjusting for traditional metabolic risk factors, hepatic steatosis, defined as a CAP ≥ 248 dB/m, was associated with low muscle mass (class I, odds ratio (OR): 1.96, 95% confidence interval (CI): 1.38–2.78; class II, OR: 3.33, 95% CI: 1.77–6.26). A dose-dependent association between the grade of steatosis and low muscle mass was also found (class I, OR: 1.88, for CAP ≥ 248, <302; OR: 2.19, in CAP ≥ 302; class II, OR: 2.33, for CAP ≥ 248, <302; OR: 6.17, in CAP ≥ 302). High liver stiffness was also significantly associated with an increased risk of low muscle mass (class I, OR: 1.97, 95% CI: 1.31–2.95; class II, OR: 2.96, 95% CI: 1.51–5.78). Conclusion: Hepatic steatosis is independently associated with low muscle mass in a dose-dependent manner. The association between hepatic steatosis and low muscle mass suggests that particular attention should be given to subjects with NAFLD for an adequate assessment of muscle mass. Full article

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

10 pages, 1370 KiB

Open AccessBrief Report

Complex Brines and Their Implications for Habitability

by Nilton O. Renno, Erik Fischer, Germán Martínez and Jennifer Hanley

Life 2021, 11(8), 847; https://doi.org/10.3390/life11080847 - 19 Aug 2021

Cited by 3 | Viewed by 2738

Abstract

There is evidence that life on Earth originated in cold saline waters around scorching hydrothermal vents, and that similar conditions might exist or have existed on Mars, Europa, Ganymede, Enceladus, and other worlds. Could potentially habitable complex brines with extremely low freezing temperatures [...] Read more.

There is evidence that life on Earth originated in cold saline waters around scorching hydrothermal vents, and that similar conditions might exist or have existed on Mars, Europa, Ganymede, Enceladus, and other worlds. Could potentially habitable complex brines with extremely low freezing temperatures exist in the shallow subsurface of these frigid worlds? Earth, Mars, and carbonaceous chondrites have similar bulk elemental abundances, but while the Earth is depleted in the most volatile elements, the Icy Worlds of the outer solar system are expected to be rich in them. The cooling of ionic solutions containing substances that likely exist in the Icy Worlds could form complex brines with the lowest eutectic temperature possible for the compounds available in them. Indeed, here, we show observational and theoretical evidence that even elements present in trace amounts in nature are concentrated by freeze–thaw cycles, and therefore contribute significantly to the formation of brine reservoirs that remain liquid throughout the year in some of the coldest places on Earth. This is interesting because the eutectic temperature of water–ammonia solutions can be as low as ~160 K, and significant fractions of the mass of the Icy Worlds are estimated to be water substance and ammonia. Thus, briny solutions with eutectic temperature of at least ~160 K could have formed where, historically, temperature have oscillated above and below ~160 K. We conclude that complex brines must exist in the shallow subsurface of Mars and the Icy Worlds, and that liquid saline water should be present where ice has existed, the temperature is above ~160 K, and evaporation and sublimation have been inhibited. Full article

(This article belongs to the Special Issue Microbial Life in the Solar System)

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15 pages, 6595 KiB

Open AccessArticle

Establishment of an Intradermal Ear Injection Model of IL-17A and IL-36γ as a Tool to Investigate the Psoriatic Cytokine Network

by David Kluwig, Sebastian Huth, Ali T. Abdallah, Carolina M. Pfaff, Katharina Fietkau, Laura Huth, Yvonne Marquardt, Jens M. Baron and Bernhard Lüscher

Life 2021, 11(8), 846; https://doi.org/10.3390/life11080846 - 19 Aug 2021

Cited by 4 | Viewed by 3414

Abstract

Psoriasis is a chronic skin disease affecting 2–3% of the global population. The proinflammatory IL-17A is a key cytokine in psoriasis. Accumulating evidence has revealed that IL-36γ plays also a pathogenic role. To understand more precisely the role of the IL-17A–IL-36γ cytokine network [...] Read more.

Psoriasis is a chronic skin disease affecting 2–3% of the global population. The proinflammatory IL-17A is a key cytokine in psoriasis. Accumulating evidence has revealed that IL-36γ plays also a pathogenic role. To understand more precisely the role of the IL-17A–IL-36γ cytokine network in skin pathology, we used an ear injection model. We injected IL-17A or IL-36γ alone and in combination into the ear pinnae of mice. This resulted in a significant increase in ear thickness measured over time. Histological evaluation of IL-17A + IL-36γ-treated skin showed a strong acanthosis, hyperparakeratosis and infiltration of neutrophils. The same histological features were found in mice after injection of IL-36γ alone, but to a lesser extent. IL-17A alone was not able to induce psoriasis-like changes. Genes encoding proteins of the S100 family, antimicrobial peptides and chemo-attractants for neutrophils were upregulated in the IL-17A + IL-36γ group. A much weaker expression was seen after the injection of each cytokine alone. These results strengthen the hypothesis that IL-17A and IL-36γ drive psoriatic inflammation via a synergistic interaction. Our established intradermal ear injection model can be utilized in the future to monitor effects of various inhibitors of this cytokine network. Full article

(This article belongs to the Special Issue Psoriasis: New Developments and Concepts in Pathogenesis and Treatment)

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11 pages, 22070 KiB

Open AccessArticle

Immediate Effects of Myofascial Release on the Thoracolumbar Fascia and Osteopathic Treatment for Acute Low Back Pain on Spine Shape Parameters: A Randomized, Placebo-Controlled Trial

by Andreas Brandl, Christoph Egner and Robert Schleip

Life 2021, 11(8), 845; https://doi.org/10.3390/life11080845 - 18 Aug 2021

Cited by 12 | Viewed by 10709

Abstract

Background: Spine shape parameters, such as leg length and kyphotic or lordotic angle, are influenced by low back pain. There is also evidence that the thoracolumbar fascia plays a role in such pathologies. This study examined the immediate effects of a myofascial release [...] Read more.

Background: Spine shape parameters, such as leg length and kyphotic or lordotic angle, are influenced by low back pain. There is also evidence that the thoracolumbar fascia plays a role in such pathologies. This study examined the immediate effects of a myofascial release (MFR) technique on the thoracolumbar fascia and of an osteopathic treatment (OMT) on postural parameters in patients with acute low back pain (aLBP). Methods: This study was a single-blind randomized placebo-controlled trial. Seventy-one subjects (43.8 ± 10.5 years) suffering from aLBP were randomly and blindedly assigned to three groups to be treated with MFR, OMT, or a placebo intervention. Spinal shape parameters (functional leg length discrepancy (fLLD), kyphotic angle, and lordotic angle) were measured before and after the intervention using video raster stereography. Results: Within the MFR group, fLLD reduced by 5.2 mm, p < 0.001 and kyphotic angle by 8.2 degrees, p < 0.001. Within the OMT group, fLLD reduced by 4.5 mm, p < 0.001, and kyphotic angle by 8.4°, p = 0.007. Conclusion: MFR and OMT have an influence on fLLD and the kyphotic angle in aLBP patients. The interventions could have a regulating effect on the impaired neuromotor control of the lumbar muscles. Full article

(This article belongs to the Special Issue Fasciae from a Molecular and Biomechanical Perspective)

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42 pages, 6508 KiB

Open AccessReview

Biologically-Based and Physiochemical Life Support and In Situ Resource Utilization for Exploration of the Solar System—Reviewing the Current State and Defining Future Development Needs

by Ryan J. Keller, William Porter, Karthik Goli, Reece Rosenthal, Nicole Butler and Jeffrey A. Jones

Life 2021, 11(8), 844; https://doi.org/10.3390/life11080844 - 18 Aug 2021

Cited by 12 | Viewed by 12076

Abstract

The future of long-duration spaceflight missions will place our vehicles and crew outside of the comfort of low-Earth orbit. Luxuries of quick resupply and frequent crew changes will not be available. Future missions will have to be adapted to low resource environments and [...] Read more.

The future of long-duration spaceflight missions will place our vehicles and crew outside of the comfort of low-Earth orbit. Luxuries of quick resupply and frequent crew changes will not be available. Future missions will have to be adapted to low resource environments and be suited to use resources at their destinations to complete the latter parts of the mission. This includes the production of food, oxygen, and return fuel for human flight. In this chapter, we performed a review of the current literature, and offer a vision for the implementation of cyanobacteria-based bio-regenerative life support systems and in situ resource utilization during long duration expeditions, using the Moon and Mars for examples. Much work has been done to understand the nutritional benefits of cyanobacteria and their ability to survive in extreme environments like what is expected on other celestial objects. Fuel production is still in its infancy, but cyanobacterial production of methane is a promising front. In this chapter, we put forth a vision of a three-stage reactor system for regolith processing, nutritional and atmospheric production, and biofuel production as well as diving into what that system will look like during flight and a discussion on containment considerations. Full article

(This article belongs to the Collection Space Life Sciences)

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14 pages, 509 KiB

Open AccessReview

Biological Hallmarks and New Therapeutic Approaches for the Treatment of PDAC

by Graziana Digiacomo, Francesco Volta, Ingrid Garajova, Rita Balsano and Andrea Cavazzoni

Life 2021, 11(8), 843; https://doi.org/10.3390/life11080843 - 18 Aug 2021

Cited by 10 | Viewed by 4100

Abstract

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest solid tumors and is estimated to become a leading cause of cancer-related death in coming years. Despite advances in surgical approaches and the emergence of new chemotherapy options, its poor prognosis has not improved [...] Read more.

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest solid tumors and is estimated to become a leading cause of cancer-related death in coming years. Despite advances in surgical approaches and the emergence of new chemotherapy options, its poor prognosis has not improved in the last decades. The current treatment for PDAC is the combination of cytotoxic chemotherapy agents. However, PDAC shows resistance to many antineoplastic therapies with rapid progression. Although PDAC represents a heterogeneous disease, there are common alterations including oncogenic mutations of KRAS, and the frequent inactivation of different cell cycle regulators including the CDKN2A tumor suppressor gene. An emerging field of investigation focuses on inhibiting the function of proteins that suppress the immune checkpoint PD-1/PD-L1, with activation of the endogenous immune response. To date, all conventional immunotherapies have been less successful in patients with PDAC compared to other tumors. The need for new targets, associated with an extended molecular analysis of tumor samples could give new pharmacological options for the treatment of PDAC. It is, therefore, important to push for a broader molecular approach in PDAC research. Here, we provide a selected summary of emerging strategy options for targeting PDAC using CDK4/6 inhibitors, RAS inhibitors, and new drug combinations with immune checkpoint agents. Full article

(This article belongs to the Section Medical Research)

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13 pages, 6252 KiB

Open AccessArticle

Single Cell Cryo-Soft X-ray Tomography Shows That Each Chlamydia Trachomatis Inclusion Is a Unique Community of Bacteria

by Patrick Phillips, James M. Parkhurst, Ilias Kounatidis, Chidinma Okolo, Thomas M. Fish, James H. Naismith, Martin A. Walsh, Maria Harkiolaki and Maud Dumoux

Life 2021, 11(8), 842; https://doi.org/10.3390/life11080842 - 18 Aug 2021

Cited by 4 | Viewed by 4252

Abstract

Chlamydiae are strict intracellular pathogens residing within a specialised membrane-bound compartment called the inclusion. Therefore, each infected cell can, be considered as a single entity where bacteria form a community within the inclusion. It remains unclear as to how the population of bacteria [...] Read more.

Chlamydiae are strict intracellular pathogens residing within a specialised membrane-bound compartment called the inclusion. Therefore, each infected cell can, be considered as a single entity where bacteria form a community within the inclusion. It remains unclear as to how the population of bacteria within the inclusion influences individual bacterium. The life cycle of Chlamydia involves transitioning between the invasive elementary bodies (EBs) and replicative reticulate bodies (RBs). We have used cryo-soft X-ray tomography to observe individual inclusions, an approach that combines 40 nm spatial resolution and large volume imaging (up to 16 µm). Using semi-automated segmentation pipeline, we considered each inclusion as an individual bacterial niche. Within each inclusion, we identifyed and classified different forms of the bacteria and confirmed the recent finding that RBs have a variety of volumes (small, large and abnormal). We demonstrate that the proportions of these different RB forms depend on the bacterial concentration in the inclusion. We conclude that each inclusion operates as an autonomous community that influences the characteristics of individual bacteria within the inclusion. Full article

(This article belongs to the Section Microbiology)

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23 pages, 1800 KiB

Open AccessReview

Impact of Physical Activity and Natural Bioactive Compounds on Endothelial Dysfunction in Chronic Kidney Disease

by Elisa Grazioli, Annalisa Romani, Giulia Marrone, Manuela Di Lauro, Claudia Cerulli, Silvia Urciuoli, Arianna Murri, Cristina Guerriero, Eliana Tranchita, Manfredi Tesauro, Attilio Parisi, Nicola Di Daniele and Annalisa Noce

Life 2021, 11(8), 841; https://doi.org/10.3390/life11080841 - 17 Aug 2021

Cited by 10 | Viewed by 3499

Abstract

Chronic kidney disease (CKD) represents a world-wide public health problem. Inflammation, endothelial dysfunction (ED) and vascular calcifications are clinical features of CKD patients that increase cardiovascular (CV) mortality. CKD-related CV disease pathogenic mechanisms are not only associated with traditional factors such as arterial [...] Read more.

Chronic kidney disease (CKD) represents a world-wide public health problem. Inflammation, endothelial dysfunction (ED) and vascular calcifications are clinical features of CKD patients that increase cardiovascular (CV) mortality. CKD-related CV disease pathogenic mechanisms are not only associated with traditional factors such as arterial hypertension and dyslipidemia, but also with ED, oxidative stress and low-grade inflammation. The typical comorbidities of CKD contribute to reduce the performance and the levels of the physical activity in nephropathic patients compared to healthy subjects. Currently, the effective role of physical activity on ED is still debated, but the available few literature data suggest its positive contribution. Another possible adjuvant treatment of ED in CKD patients is represented by natural bioactive compounds (NBCs). Among these, minor polar compounds of extra virgin olive oil (hydroxytyrosol, tyrosol and oleocanthal), polyphenols, and vitamin D seem to exert a beneficial role on ED in CKD patients. The objective of the review is to evaluate the effectiveness of physical exercise protocols and/or NBCs on ED in CKD patients. Full article

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13 pages, 3385 KiB

Open AccessArticle

Chemoembolization for Single Large Hepatocellular Carcinoma with Preserved Liver Function: Analysis of Factors Predicting Clinical Outcomes in a 302 Patient Cohort

by Gun Ha Kim, Jin Hyoung Kim, Ju Hyun Shim, Heung-Kyu Ko, Hee Ho Chu, Ji Hoon Shin, Hyun-Ki Yoon, Gi-Young Ko and Dong Il Gwon

Life 2021, 11(8), 840; https://doi.org/10.3390/life11080840 - 17 Aug 2021

Cited by 12 | Viewed by 2986

Abstract

The purpose of this study was to define the role of transcatheter arterial chemoembolization (TACE) in patients with a single large hepatocellular carcinoma (HCC) and define the patient groups benefiting from TACE. Treatment-naïve patients with preserved liver function who received TACE as the [...] Read more.

The purpose of this study was to define the role of transcatheter arterial chemoembolization (TACE) in patients with a single large hepatocellular carcinoma (HCC) and define the patient groups benefiting from TACE. Treatment-naïve patients with preserved liver function who received TACE as the first-line treatment for single large (>5 cm) HCC without macrovascular invasion and extrahepatic metastasis between 2007 and 2019 were retrospectively analyzed. Overall survival, progression-free survival, radiologic tumor response, complications, and predictors of survival were analyzed using multivariate analysis, and then a pretreatment risk-prediction model was created using the four predictive factors of tumor size, tumor type, ALBI grade, and ECOG performance status. Patients with scores of 0 (n = 54), 1–2 (n = 170), and 3–6 (n = 78) according to the model were classified as low-, intermediate-, and high-risk, respectively. The corresponding median OS values were 141, 55, and 28 months, respectively. The percentage of major complications increased as tumor size increased (4–21%). Asymptomatic, nodular HCC patients with a tumor size of 5–7 cm and ALBI grade 1 benefited the most from TACE. By contrast, the value of TACE in the treatment of single huge HCC (>10 cm) with high complication rates remains unclear. Full article

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

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19 pages, 4676 KiB

Open AccessReview

Autophagy Modulators in Cancer: Focus on Cancer Treatment

by Hye Jin Nam

Life 2021, 11(8), 839; https://doi.org/10.3390/life11080839 - 17 Aug 2021

Cited by 14 | Viewed by 3276

Abstract

Uncontrolled autophagy has been associated with the development and progression of various cancers that are resistant to cancer therapy. Therefore, many efforts to modulate uncontrolled autophagy as a cancer treatment have been attempted, from basic science to clinical trials. However, it remains difficult [...] Read more.

Uncontrolled autophagy has been associated with the development and progression of various cancers that are resistant to cancer therapy. Therefore, many efforts to modulate uncontrolled autophagy as a cancer treatment have been attempted, from basic science to clinical trials. However, it remains difficult to equally apply autophagy modulators to cancer therapy because autophagy is a double-edged sword in cancer: it can be tumor-suppressive or tumor-protective. Therefore, the precise mechanisms of autophagy modulators and their varied responsiveness to each cancer type should be addressed in detail. This study will describe the precise mechanisms of developing various autophagy modulators, their current therapeutic applications and future perspectives. Full article

(This article belongs to the Special Issue Autophagy and Cancer 2021)

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14 pages, 776 KiB

Open AccessReview

Towards Next Generation Biomarkers in Natural Killer/T-Cell Lymphoma

by Jason Yongsheng Chan, Jing Quan Lim and Choon Kiat Ong

Life 2021, 11(8), 838; https://doi.org/10.3390/life11080838 - 16 Aug 2021

Cited by 5 | Viewed by 3644

Abstract

Natural killer/T-cell lymphoma (NKTCL) is an Epstein–Barr virus-associated non-Hodgkin lymphoma linked to an aggressive clinical course and poor prognosis. Despite an improvement in survival outcomes with the incorporation of novel agents including immune checkpoint inhibitors in the treatment of NKTCL, a significant proportion [...] Read more.

Natural killer/T-cell lymphoma (NKTCL) is an Epstein–Barr virus-associated non-Hodgkin lymphoma linked to an aggressive clinical course and poor prognosis. Despite an improvement in survival outcomes with the incorporation of novel agents including immune checkpoint inhibitors in the treatment of NKTCL, a significant proportion of patients still relapse or remain refractory to treatment. Several clinical prognostic models have been developed for NKTCL patients treated in the modern era, though the optimal approach to risk stratification remains to be determined. Novel molecular biomarkers derived from multi-omic profiling have recently been developed, with the potential to improve diagnosis, prognostication and treatment of this disease. Notably, a number of potential biomarkers have emerged from a better understanding of the tumor immune microenvironment and inflammatory responses. This includes a recently described 3′UTR structural variant in the PD-L1 gene, which confers susceptibility to checkpoint immunotherapy. In this review, we summarize the biomarker landscape of NKTCL and highlight emerging biomarkers with the potential for clinical implementation. Full article

(This article belongs to the Special Issue Updates on Natural Killer/T‐cell Lymphomas)

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