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Life
Volume 12
Issue 9
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Life, Volume 12, Issue 9 (September 2022) – 169 articles

Cover Story (view full-size image): Cutaneous melanoma (CM) is responsible for most skin cancer-related deaths worldwide. Its origin is closely linked to the accumulation of UV-induced somatic mutations in melanocytes present in normal skin, nevi or dysplastic nevi. Mutations in TP53, NOTCH and FAT1 are common in normal skin, while mutations in BRAF and NRAS and in BRAF, TP53, CDKN2A, PTEN and RAS are characteristic of nevi and dysplastic nevi, respectively. However, a higher mutational burden on cancer-driving genes is required to convert normal melanocytes into malignant ones, and boost their progression towards more advanced stages. Mutations in BRAF, NRAS, KIT or NF1 are distinctive of early stages of CM, while CM progression to invasive stages is associated with mutations in TP53, PTEN, CDKN2A and TERT. Metastatic processes also include the dysregulation of genomic integrity. View this paper
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14 pages, 2914 KiB  
Article
Effects of Secretoneurin and Gonadotropin-Releasing Hormone Agonist on the Spawning of Captive Greater Amberjack (Seriola dumerili)
by Song Yanlong, Jiang Yinjun, Chen Ji, Tao Binbin, Xu Wen, Huang Yang, Li Guangli, Chunhua Zhu and Hu Wei
Life 2022, 12(9), 1457; https://doi.org/10.3390/life12091457 - 19 Sep 2022
Cited by 2 | Viewed by 2336
Abstract
The greater amberjack (Seriola dumerili), a pelagic marine species with a global distribution, has considerable worldwide potential as an aquaculture species. However, difficulties have been encountered in inducing spontaneous spawning in cultured fish stocks. In this study, we analysed the key [...] Read more.
The greater amberjack (Seriola dumerili), a pelagic marine species with a global distribution, has considerable worldwide potential as an aquaculture species. However, difficulties have been encountered in inducing spontaneous spawning in cultured fish stocks. In this study, we analysed the key regulatory factors, secretoneurin (SN) and gonadotropin-releasing hormone (GnRH), in greater amberjack. Active peptides of SN and GnRH, SdSNa, and SdGnRH, respectively, were obtained by comparative analysis of homologous proteins from different species. Amino acid substitutions of the SdGnRH decapeptide at position 6 with a dextrorotatory (D) amino acid and at position 10 with an ethylamide group yielded a super-active agonist (SdGnRHa). The injection of SdSNa and SdGnRHa elevated luteinizing hormone, thyroid-stimulating hormone, and oxytocin levels in the sera of sexually mature fish, whereas it reduced the level of follicle-stimulating hormone. Furthermore, in response to the SdSNa and SdGnRHa injections, we detected an increase in the expression of genes associated with oocyte development and spermatogenesis. We established that the greater amberjack cultured along the southern coast of China reached sexual maturity at three years of age, and its reproductive season extended from February to April. Spawning of the cultured greater amberjack was successfully induced with a single injection of SdGnRHa/SdSN/DOM/HCG. Our findings indicate that similar to GnRHa, SNa is a potential stimulator of reproduction that can be used to artificially induce spawning in marine fish. Full article
(This article belongs to the Special Issue Sex Determination and Gonad Development: From Mechanism to Application)
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31 pages, 4597 KiB  
Systematic Review
Identification of Suitable Drug Combinations for Treating COVID-19 Using a Novel Machine Learning Approach: The RAIN Method
by Aliakbar Kiaei, Nader Salari, Mahnaz Boush, Kamran Mansouri, Amin Hosseinian-Far, Hooman Ghasemi and Masoud Mohammadi
Life 2022, 12(9), 1456; https://doi.org/10.3390/life12091456 - 19 Sep 2022
Cited by 2 | Viewed by 2830
Abstract
COVID-19 affects several human genes, each with its own p-value. The combination of drugs associated with these genes with small p-values may lead to an estimation of the combined p-value between COVID-19 and some drug combinations, thereby increasing the effectiveness [...] Read more.
COVID-19 affects several human genes, each with its own p-value. The combination of drugs associated with these genes with small p-values may lead to an estimation of the combined p-value between COVID-19 and some drug combinations, thereby increasing the effectiveness of these combinations in defeating the disease. Based on human genes, we introduced a new machine learning method that offers an effective drug combination with low combined p-values between them and COVID-19. This study follows an improved approach to systematic reviews, called the Systematic Review and Artificial Intelligence Network Meta-Analysis (RAIN), registered within PROSPERO (CRD42021256797), in which, the PRISMA criterion is still considered. Drugs used in the treatment of COVID-19 were searched in the databases of ScienceDirect, Web of Science (WoS), ProQuest, Embase, Medline (PubMed), and Scopus. In addition, using artificial intelligence and the measurement of the p-value between human genes affected by COVID-19 and drugs that have been suggested by clinical experts, and reported within the identified research papers, suitable drug combinations are proposed for the treatment of COVID-19. During the systematic review process, 39 studies were selected. Our analysis shows that most of the reported drugs, such as azithromycin and hydroxyl-chloroquine on their own, do not have much of an effect on the recovery of COVID-19 patients. Based on the result of the new artificial intelligence, on the other hand, at a significance level of less than 0.05, the combination of the two drugs therapeutic corticosteroid + camostat with a significance level of 0.02, remdesivir + azithromycin with a significance level of 0.03, and interleukin 1 receptor antagonist protein + camostat with a significance level 0.02 are considered far more effective for the treatment of COVID-19 and are therefore recommended. Additionally, at a significance level of less than 0.01, the combination of interleukin 1 receptor antagonist protein + camostat + azithromycin + tocilizumab + oseltamivir with a significance level of 0.006, and the combination of interleukin 1 receptor antagonist protein + camostat + chloroquine + favipiravir + tocilizumab7 with corticosteroid + camostat + oseltamivir + remdesivir + tocilizumab at a significant level of 0.009 are effective in the treatment of patients with COVID-19 and are also recommended. The results of this study provide sets of effective drug combinations for the treatment of patients with COVID-19. In addition, the new artificial intelligence used in the RAIN method could provide a forward-looking approach to clinical trial studies, which could also be used effectively in the treatment of diseases such as cancer. Full article
(This article belongs to the Special Issue COVID-19 and Long-COVID-19: Pathogenesis, Clinical Manifestation, and Therapeutic Options)
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18 pages, 2124 KiB  
Review
Recent Advances in the Study of Gas Vesicle Proteins and Application of Gas Vesicles in Biomedical Research
by Felicitas Pfeifer
Life 2022, 12(9), 1455; https://doi.org/10.3390/life12091455 - 19 Sep 2022
Cited by 12 | Viewed by 4086
Abstract
The formation of gas vesicles has been investigated in bacteria and haloarchaea for more than 50 years. These air-filled nanostructures allow cells to stay at a certain height optimal for growth in their watery environment. Several gvp genes are involved and have been [...] Read more.
The formation of gas vesicles has been investigated in bacteria and haloarchaea for more than 50 years. These air-filled nanostructures allow cells to stay at a certain height optimal for growth in their watery environment. Several gvp genes are involved and have been studied in Halobacterium salinarum, cyanobacteria, Bacillus megaterium, and Serratia sp. ATCC39006 in more detail. GvpA and GvpC form the gas vesicle shell, and additional Gvp are required as minor structural proteins, chaperones, an ATP-hydrolyzing enzyme, or as gene regulators. We analyzed the Gvp proteins of Hbt. salinarum with respect to their protein–protein interactions, and developed a model for the formation of these nanostructures. Gas vesicles are also used in biomedical research. Since they scatter waves and produce ultrasound contrast, they could serve as novel contrast agent for ultrasound or magnetic resonance imaging. Additionally, gas vesicles were engineered as acoustic biosensors to determine enzyme activities in cells. These applications are based on modifications of the surface protein GvpC that alter the mechanical properties of the gas vesicles. In addition, gas vesicles have been decorated with GvpC proteins fused to peptides of bacterial or viral pathogens and are used as tools for vaccine development. Full article
(This article belongs to the Collection Feature Review Papers for Life)
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14 pages, 1071 KiB  
Article
Exogenous Nitric Oxide and Silicon Applications Alleviate Water Stress in Apricots
by Asuman Gundogdu Bakır, Ibrahim Bolat, Kubra Korkmaz, Md. Mahadi Hasan and Ozkan Kaya
Life 2022, 12(9), 1454; https://doi.org/10.3390/life12091454 - 19 Sep 2022
Cited by 8 | Viewed by 2234
Abstract
Many plants confront several environmental stresses including heat, water stress, drought, salinity and high-metal concentrations that are crucial in defining plant productivity at different stages of their life cycle. Nitric oxide (NO) and Silicon (Si) are very effective molecules related in most of [...] Read more.
Many plants confront several environmental stresses including heat, water stress, drought, salinity and high-metal concentrations that are crucial in defining plant productivity at different stages of their life cycle. Nitric oxide (NO) and Silicon (Si) are very effective molecules related in most of them and in varied biochemical events that have proven to be protective during cellular injury caused by some stress conditions like water stress. In the current work, we studied the effect of Si and NO alone and NO + Si interactive application on the response of plants exposed to water deficiency and well-watered plants for the Milord apricot variety. Water stress caused a reduce in chlorophyll content, dry and fresh weight, leaf area, stomatal conductivity, leaf relative water content and nutrient elements, while it caused an increase in leaf temperature, leaf proline, leaf malondialdehyde (MDA) content and membrane permeability. Si, NO and Si + NO combination treatments under water stress conditions significantly decreased the adverse effects of water stress on leaf temperature, leaf area, dry and fresh weight, stomata conductivity, relative water content, membrane permeability, L-proline and MDA content. The shoot dry weight, chlorophyll content, stomata conductivity and leaf relative water content in Si + NO treated apricot saplings increased by 59%, 55%, 12% and 8%, respectively. Combined treatment (Si + NO) was detected to be more effective than single applications (Si or NO) on some physiological, biochemical, morphological and nutritional properties of apricot under water stress conditions. Full article
(This article belongs to the Section Plant Science)
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21 pages, 3733 KiB  
Article
Genomic Analysis of LEA Genes in Carica papaya and Insight into Lineage-Specific Family Evolution in Brassicales
by Zhi Zou, Jingyuan Guo, Yujiao Zheng, Yanhua Xiao and Anping Guo
Life 2022, 12(9), 1453; https://doi.org/10.3390/life12091453 - 19 Sep 2022
Cited by 5 | Viewed by 2077
Abstract
Late embryogenesis abundant (LEA) proteins comprise a diverse superfamily involved in plant development and stress responses. This study presents a first genome-wide analysis of LEA genes in papaya (Carica papaya L., Caricaceae), an economically important tree fruit crop widely cultivated in the [...] Read more.
Late embryogenesis abundant (LEA) proteins comprise a diverse superfamily involved in plant development and stress responses. This study presents a first genome-wide analysis of LEA genes in papaya (Carica papaya L., Caricaceae), an economically important tree fruit crop widely cultivated in the tropics and subtropics. A total of 28 members were identified from the papaya genome, which belong to eight families with defined Pfam domains, i.e., LEA_1 (3), LEA_2 (4), LEA_3 (5), LEA_4 (5), LEA_5 (2), LEA_6 (2), DHN (4), and SMP (3). The family numbers are comparable to those present in Ricinus communis (Euphorbiaceae, 28) and Moringa oleifera (Moringaceae, 29), but relatively less than that found in Moringa oleifera (Cleomaceae, 39) and Arabidopsis thaliana (Brassicaceae, 51), implying lineage-specific evolution in Brassicales. Indeed, best-reciprocal-hit-based sequence comparison and synteny analysis revealed the presence of 29 orthogroups, and significant gene expansion in Tarenaya and Arabidopsis was mainly contributed by whole-genome duplications that occurred sometime after their split with the papaya. Though a role of transposed duplication was also observed, tandem duplication was shown to be a key contributor in gene expansion of most species examined. Further comparative analyses of exon-intron structures and protein motifs supported fast evolution of this special superfamily, especially in Arabidopsis. Transcriptional profiling revealed diverse expression patterns of CpLEA genes over various tissues and different stages of developmental fruit. Moreover, the transcript level of most genes appeared to be significantly regulated by drought, cold, and salt stresses, corresponding to the presence of cis-acting elements associated with stress response in their promoter regions. These findings not only improve our knowledge on lineage-specific family evolution in Brassicales, but also provide valuable information for further functional analysis of LEA genes in papaya. Full article
(This article belongs to the Special Issue Plant Biotic and Abiotic Stresses)
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18 pages, 2450 KiB  
Article
Study on Cytotoxic and Genotoxic Potential of Bulgarian Rosa damascena Mill. and Rosa alba L. Hydrosols—In Vivo and In Vitro
by Tsvetelina Gerasimova, Gabriele Jovtchev, Svetla Gateva, Margarita Topashka-Ancheva, Alexander Stankov, Tsveta Angelova, Ana Dobreva and Milka Mileva
Life 2022, 12(9), 1452; https://doi.org/10.3390/life12091452 - 19 Sep 2022
Cited by 7 | Viewed by 2711
Abstract
The Rosa alba L. and Rosa damascena Mill. growing in Bulgaria are known for their extremely fine essential oil and valuable hydrosols. Irrespectively of its wide use in human life, little research exists on the cytotoxic and genotoxic activity of the hydrosols. This [...] Read more.
The Rosa alba L. and Rosa damascena Mill. growing in Bulgaria are known for their extremely fine essential oil and valuable hydrosols. Irrespectively of its wide use in human life, little research exists on the cytotoxic and genotoxic activity of the hydrosols. This set our goal to conduct cytogenetic analyses to study these effects. A complex of classical cytogenetic methods was applied in three types of experimental test systems—higher plant in vivo, ICR mice in vivo, and human lymphocytes in vitro. Mitotic index, PCE/(PCE + NCE) ratio, and nuclear division index were used as endpoints for cytotoxicity and for genotoxicity—induction of chromosome aberrations and micronuclei. Rose hydrosol treatments range in concentrations from 6% to 20%. It was obtained that both hydrosols did not show considerable cytotoxic and genotoxic effects. These effects depend on the type of the tested rose hydrosols, the concentrations applied in the experiments, and the sensitivity and specificity of the test systems used. Human lymphocytes in vitro were the most sensitive to hydrosols, followed by higher plant and animal cells. Chromosomal aberrations and micronucleus assays suggested that R. damascena and R. alba hydrosols at applied concentrations possess low genotoxic risk. Due to the overall low values in terms of cytotoxic and/or genotoxic effects in all test systems, hydrosols are promising for further use in various areas of human life. Full article
(This article belongs to the Special Issue The Role of Renewable Resources for Ecology and Human Health)
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17 pages, 7352 KiB  
Article
Evaluation of the Antihyperglycemic and Antihyperlipidemic Activity of Saussurea hypoleuca Root in Alloxan-Induced Diabetes in Rat Model and Correlation to Its Major Secondary Metabolites
by Numera Arshad, Saiqa Ishtiaq, Sairah Hafeez Kamran, Muhammad Sajid-ur Rehman, Shehla Akbar, Saira Rehman, Sarah Rehman, Rawan H. Hareeri, Sana A. Fadil, Fadia S. Youssef and Sameh S. Elhady
Life 2022, 12(9), 1451; https://doi.org/10.3390/life12091451 - 19 Sep 2022
Viewed by 2558
Abstract
Saussurea hypoleuca belongs to the family Asteraceae, which has previously shown hepatoprotective, anticancer, and antioxidant activity. This study aimed to evaluate the antihyperglycemic and antihyperlipidemic activity of its root methanol extract and various fractions for the first time. This was performed using alloxan-induced [...] Read more.
Saussurea hypoleuca belongs to the family Asteraceae, which has previously shown hepatoprotective, anticancer, and antioxidant activity. This study aimed to evaluate the antihyperglycemic and antihyperlipidemic activity of its root methanol extract and various fractions for the first time. This was performed using alloxan-induced diabetes in the rat model for both short, and long-term periods using different administration doses. Different biochemical parameters were studied and further consolidated by histopathological examination and in silico molecular modeling. The results showed that in the long-term study, at a dose of 400 mg/kg b.wt, the ethyl acetate fraction caused a pronounced reduction in fasting blood glucose level (FBG) and glycated hemoglobin (HbA1c) by 77.2% and 36.8%, respectively, compared to the diabetic group. This was confirmed by the histopathological examination of the animals’ pancreatic sections. The ethyl acetate fraction also showed a reduction in total cholesterol (TC), total glycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels. It improved kidney and liver functions, causing a reduction in aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine transaminase (ALT), urea, and creatinine levels. This is mainly attributed to its richness in secondary metabolites. Molecular docking showed that all the tested compounds showed certain inhibitory potential towards human α-glucosidase (HAG) and ATP citrate lyase (ACL). Thus, Saussurea hypoleuca roots can help in the management of hyperglycemia, hyperlipidemia, and hepatic and kidney dysfunction. Full article
(This article belongs to the Collection The Role of Bioactive Natural Compounds in the Treatment of Diseases)
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9 pages, 882 KiB  
Article
Cordyceps militaris Inhibited Angiotensin-Converting Enzyme through Molecular Interaction between Cordycepin and ACE C-Domain
by Mónica A. Valdez-Solana, Iván A. Corral-Guerrero, Alfredo Téllez-Valencia, Claudia Avitia-Domínguez, Jorge A. Meza-Velázquez, Atahualpa Guzmán de Casa and Erick Sierra-Campos
Life 2022, 12(9), 1450; https://doi.org/10.3390/life12091450 - 19 Sep 2022
Cited by 3 | Viewed by 2771
Abstract
One of the most important therapeutic modalities for the management of hypertension is the inhibition of the angiotensin-converting enzyme (ACE). Cordyceps militaris has received substantial attention because to its therapeutic potential and biological value. To gather information about the antihypertensive properties of C. [...] Read more.
One of the most important therapeutic modalities for the management of hypertension is the inhibition of the angiotensin-converting enzyme (ACE). Cordyceps militaris has received substantial attention because to its therapeutic potential and biological value. To gather information about the antihypertensive properties of C. militaris, the ACE inhibitory activity was evaluated. An ethanolic extract of the fruiting body of C. militaris was obtained, and the extract was separated by UHPLC method with a fluorescence detector for the quantification of cordycepin and adenosine. The ethanolic extract had a considerably higher cordycepin level. Additionally, an in vitro kinetic analysis was carried out to find out how much C. militaris extract inhibited ACE. This extract exhibited non-competitive inhibition on ACE. The Ki value of the C. militaris extract against ACE was found to be 8.7 µg/mL. To the best of our knowledge, this is the first report of the analysis of a protein cavity together with molecular docking carried out to comprehend the intermolecular interactions between cordycepin and the ACE C-domain, which impact the spatial conformation of the enzyme and reduce its capacity to break down the substrate. According to a molecular docking, hydrogen bonding interactions between the chemicals and the ACE S2’ subsite are primarily responsible for cordycepin inhibition at the ACE C domain. All these findings suggest that C. militaris extract are a kind of natural ACE inhibitor, and cordycepin has the potential as an ACE inhibitor. Full article
(This article belongs to the Section Biochemistry, Biophysics and Computational Biology)
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11 pages, 828 KiB  
Article
The Pre-Discharge Oxygen Uptake Efficiency Slope Predicts One-Year Cardiovascular Events in Acute Decompensated Heart Failure Patients
by I-Ching Huang, Yi-Jen Chen, Chia-Hsin Chen, Wei-Chun Huang and Ko-Long Lin
Life 2022, 12(9), 1449; https://doi.org/10.3390/life12091449 - 19 Sep 2022
Cited by 1 | Viewed by 2503
Abstract
(1) Background: Heart failure is a complex disease leading to functional disability. Cardiopulmonary exercise testing (CPET) is the gold standard in assessing aerobic capacity and formulating function-based prognostic stratification; however, patients with acute heart failure after medical treatment usually remain with markedly reduced [...] Read more.
(1) Background: Heart failure is a complex disease leading to functional disability. Cardiopulmonary exercise testing (CPET) is the gold standard in assessing aerobic capacity and formulating function-based prognostic stratification; however, patients with acute heart failure after medical treatment usually remain with markedly reduced exercise capacity, leading to early termination of CPET with submaximal testing results. The current study aimed to assess the cardiorespiratory fitness and characteristics of CPET variables of patients after acute heart failure treatment and determine potential CPET variables with prognostic value. (2) Methods: We recruited patients during hospitalization after management of acute heart failure, and pre-discharge CPET was performed. All enrolled patients were followed for one year for major adverse cardiovascular events (MACE). (3) Results: 85 patients were enrolled, with average left ventricular ejection fraction of 30.52%, and peak oxygen consumption of 10.85 mL/min/kg at baseline. The one-year MACE was 50%. Oxygen uptake efficiency slope (OUES) was a significant event predictor, with lower one-year MACE in those with OUES ≥ 1.25 (p < 0.001). Cox regression analysis showed a 5.421-fold increased risk of MACE in those with OUES < 1.25 (p = 0.004). (4) Conclusions: The current results suggested OUES is a significant prognostic indicator in patients with acute heart failure. This also emphasized the critical role of CPET in patients with heart failure for prognostic stratification. Full article
(This article belongs to the Special Issue Physical Medicine and Rehabilitation: Trends and Applications)
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13 pages, 1254 KiB  
Review
Cardiac Troponins as Biomarkers of Cardiac Myocytes Damage in Case of Arterial Hypertension: From Pathological Mechanisms to Predictive Significance
by Aleksey Michailovich Chaulin
Life 2022, 12(9), 1448; https://doi.org/10.3390/life12091448 - 19 Sep 2022
Cited by 3 | Viewed by 2552
Abstract
Background. Many pathological conditions of both cardiovascular and non-cardiac origin in the course of their development cause damage to contractile cardiac muscle cells—cardiac myocytes (CMCs). One of the most sensitive and specific criteria for detecting CMCs are cardiac troponins (CTs), which are regulatory [...] Read more.
Background. Many pathological conditions of both cardiovascular and non-cardiac origin in the course of their development cause damage to contractile cardiac muscle cells—cardiac myocytes (CMCs). One of the most sensitive and specific criteria for detecting CMCs are cardiac troponins (CTs), which are regulatory protein molecules that are released into the blood serum from CMCs upon their death or damage. New (high-sensitive) methods for detecting CTs allow the detection of minor CMCs damages at the earliest stages of cardiovascular diseases and can therefore change the understanding of disease development mechanisms and open up new diagnostic possibilities. One of the most common and dangerous early diseases of the cardiovascular system is arterial hypertension. The purpose of this paper is to summarize the pathophysiological mechanisms underlying CMCs damage and CTs release into the bloodstream in the case of arterial hypertension and to state the clinical significance of increased CTs levels in patients with arterial hypertension. Materials and methods. This is a descriptive review, which was prepared using the following databases: Embase, Pubmed/Medline and Web of Science. The following key words were used in the literature search: “myocardial injury” and “arterial hypertension” in combination with the terms “cardiac troponins” and “mechanisms of increase”. Conclusions. According to a literature analysis, CMCs damage and CTs release in the case of arterial hypertension occur according to the following pathophysiological mechanisms: myocardial hypertrophy, CMCs apoptosis, damage to the CMC cell membrane and increase in its permeability for CTs molecules, as well as changes in the glomerular filtration rate. Most often, increased CTs serum levels in case of arterial hypertension indicate an unfavorable prognosis. Data on the CTs predictive significance in case of arterial hypertension open the prospects for the use of these biomarkers in the choice of patient management plans. Full article
(This article belongs to the Section Medical Research)
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16 pages, 1215 KiB  
Article
The Predictive Value of Systemic Inflammatory Markers, the Prognostic Nutritional Index, and Measured Vessels’ Diameters in Arteriovenous Fistula Maturation Failure
by Réka Kaller, Emil Marian Arbănași, Adrian Vasile Mureșan, Septimiu Voidăzan, Eliza Mihaela Arbănași, Emőke Horváth, Bogdan Andrei Suciu, Ioan Hosu, Ioana Halmaciu, Klara Brinzaniuc and Eliza Russu
Life 2022, 12(9), 1447; https://doi.org/10.3390/life12091447 - 18 Sep 2022
Cited by 28 | Viewed by 3005
Abstract
Background: An arteriovenous fistula (AVF) is the first-line vascular access pathway for patients diagnosed with end-stage renal disease (ESRD). In planning vascular access, it is necessary to check the diameters of the venous and arterial components for satisfactory long-term results. Furthermore, the mechanism [...] Read more.
Background: An arteriovenous fistula (AVF) is the first-line vascular access pathway for patients diagnosed with end-stage renal disease (ESRD). In planning vascular access, it is necessary to check the diameters of the venous and arterial components for satisfactory long-term results. Furthermore, the mechanism underlying the maturation failure and short-term patency in cases of AVFs is not fully known. This study aims to verify the predictive role of inflammatory biomarkers (the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic inflammatory index (SII), and C-reactive protein (CRP)), Ca-P product, the prognostic nutritional index (PNI), and the diameters of the venous and arterial components in the failure of AVF maturation. Methods: The present study was designed as an observational, analytical, and retrospective cohort study with a longitudinal follow-up, and included all patients with a diagnosis of ESRD that were admitted to the Vascular Surgery Clinic of the Targu Mures Emergency County Hospital, Romania, between January 2019 and December 2021. Results: The maturation of AVF at 6 weeks was clearly lower in cases of patients in the high-NLR (31.88% vs. 91.36%; p < 0.0001), high-PLR (46.94% vs. 85.55%; p < 0.0001), high-SII (44.28% vs. 88.89%; p < 0.0001), high-CRP (46.30% vs. 88.73%; p < 0.0001), high-Ca-P product (40.43% vs. 88.46%; p < 0.0001), and low-PNI (34.78% vs. 91.14%; p < 0.0001) groups, as well as in patients with a lower radial artery (RA) diameter (40% vs. 94.87%; p = 0.0009), cephalic vein (CV) diameter (44.82% vs. 97.14%; p = 0.0001) for a radio-cephalic AVF (RC-AVF), and brachial artery (BA) diameter (30.43% vs. 89.47%; p < 0.0001) in addition to CV diameter (40% vs. 94.59%; p < 0.0001) for a brachio-cephalic AVF (BC-AVF), respectively. There was also a significant increase in early thrombosis and short-time mortality in the same patients. A multivariate analysis showed that a baseline value for the NLR, PLR, SII, CRP, Ca-P product, and PNI was an independent predictor of adverse outcomes for all of the recruited patients. Furthermore, for all patients, a high baseline value for vessel diameter was a protective factor against any negative events during the study period, except for RA diameter in mortality (p = 0.16). Conclusion: Our findings concluded that higher NLR, PLR, SII, CRP, Ca-P product, and PNI values determined preoperatively were strongly predictive of AVF maturation failure, early thrombosis, and short-time mortality. Moreover, a lower baseline value for vessel diameter was strongly predictive of AVF maturation failure and early thrombosis. Full article
(This article belongs to the Section Medical Research)
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15 pages, 1137 KiB  
Article
Variation in Phenolic Profile, Antioxidant, and Anti-Inflammatory Activities of Salvadora oleoides Decene. and Salvadora persica L. Fruits and Aerial Part Extracts
by Arifa Khanam, Ashfaq Ahmad, Neelam Iftikhar, Qasim Ali, Tabinda Fatima, Farhan Khashim Alswailmi, Abdullah Ijaz Hussain, Sulaiman Mohammed Abdullah Alnasser and Jamshaid Akhtar
Life 2022, 12(9), 1446; https://doi.org/10.3390/life12091446 - 18 Sep 2022
Cited by 5 | Viewed by 2557
Abstract
(1) Background: The objective of this study was to investigate the potential of Salvadora oleoides (S. oleoides) and Salvadora persica (S. persica) polyphenols as antioxidant and anti-inflammatory agents. (2) Methods: Aerial parts and fruits of S. oleoides and S. [...] Read more.
(1) Background: The objective of this study was to investigate the potential of Salvadora oleoides (S. oleoides) and Salvadora persica (S. persica) polyphenols as antioxidant and anti-inflammatory agents. (2) Methods: Aerial parts and fruits of S. oleoides and S. persica were collected from the periphery of District Bhakkar, Punjab, Pakistan. Methanol extracts were prepared using the Soxhlet extraction technique. Extract yield varied from 8.15 to 19.6 g/100 g dry plant material. RP-HPLC revealed the detection of thirteen phenolic aids and five flavonoids. Gallic acid, hydroxy benzoic acid, chlorogenic acid, and cinamic acid were the major phenolic acids, whereas catechin, rutin, and myricetin were the flavonoids detected. (3) Results: Maximum total phenolic contents (TPCs) (22.2 mg/g of dry plant material) and total flavonoid contents (TFCs) (6.17 mg/g of dry plant material) were found in the fruit extract of S. persica, and the minimum TPC (11.9 mg/g) and TFC (1.72 mg/g) were found in the aerial part of S. oleoides. The fruit extract of S. persica showed the highest DPPH radical scavenging activity. In vivo anti-inflammatory activity of all the extracts was performed on albumin-induced rat paw edema that was comparable with the standard indomethacin; S. persica fruit extract showed remarkable anti-inflammatory activity. Analgesic activity of aerial part and fruit extracts of S. oleoides and S. persica was investigated using a mouse model, and the results showed that maximum possible analgesia of fruit extracts of S. persica was 53.44%, which is better than the PC group (52.98%). (4) Conclusions: The variations in the antioxidant, anti-inflammatory, and analgesic activities of methanolic extracts of S. oleoides and S. persica were found to be significant, and they have therapeutic potential as antioxidant, analgesic, and anti-inflammatory agents. Full article
(This article belongs to the Special Issue Plants as a Promising Biofactory for Bioactive Compounds)
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11 pages, 1642 KiB  
Article
Structural Insights into Mouse H-FABP
by Lili Wang, Haoran Zhang, Panjing Lv, Yan Li, Maikun Teng, Yahui Liu and Donghai Wu
Life 2022, 12(9), 1445; https://doi.org/10.3390/life12091445 - 16 Sep 2022
Cited by 1 | Viewed by 2238
Abstract
Intracellular fatty acid-binding proteins are evolutionarily highly conserved proteins. The major functions and responsibilities of this family are the regulation of FA uptake and intracellular transport. The structure of the H-FABP ortholog from mouse (Mus musculus) had not been revealed at [...] Read more.
Intracellular fatty acid-binding proteins are evolutionarily highly conserved proteins. The major functions and responsibilities of this family are the regulation of FA uptake and intracellular transport. The structure of the H-FABP ortholog from mouse (Mus musculus) had not been revealed at the time this study was completed. Thus, further exploration of the structural properties of mouse H-FABP is expected to extend our knowledge of the model animal’s molecular mechanism of H-FABP function. Here, we report the high-resolution crystal structure and the NMR characterization of mouse H-FABP. Our work discloses the unique structural features of mouse H-FABP, offering a structural basis for the further development of small-molecule inhibitors for H-FABP. Full article
(This article belongs to the Special Issue Application of Nuclear Magnetic Resonance Method in Protein Research)
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18 pages, 3307 KiB  
Article
Usnic Acid Isolated from Usnea antarctica (Du Rietz) Reduced In Vitro Angiogenesis in VEGF- and bFGF-Stimulated HUVECs and Ex Ovo in Quail Chorioallantoic Membrane (CAM) Assay
by Klaudia Petrová, Miriam Bačkorová, Zuzana Demčišáková, Eva Petrovová, Michal Goga, Mária Vilková, Richard Frenák, Martin Bačkor, Ján Mojžiš and Martin Kello
Life 2022, 12(9), 1444; https://doi.org/10.3390/life12091444 - 16 Sep 2022
Cited by 7 | Viewed by 2703
Abstract
Natural products include a diverse set of compounds of drug discovery that are currently being actively used to target tumor angiogenesis. In the present study, we evaluated the anti-angiogenic activities of secondary metabolite usnic acid isolated from Usena antarctica. We investigated the in [...] Read more.
Natural products include a diverse set of compounds of drug discovery that are currently being actively used to target tumor angiogenesis. In the present study, we evaluated the anti-angiogenic activities of secondary metabolite usnic acid isolated from Usena antarctica. We investigated the in vitro effects on proliferation, migration, and tube formation of VEGF- and bFGF-stimulated HUVECs. Ex ovo anti-angiogenic activity was evaluated using the CAM assay. Our findings demonstrated that usnic acid in the concentration of 33.57 µM inhibited VEGF (25 ng/mL) and bFGF (30 ng/mL)-induced HUVECs proliferation, migration, and tube formation. The ex ovo CAM model was used to confirm the results obtained from in vitro studies. VEGF- and bFGF-induced vessel formation was inhibited by usnic acid after 72 h in over 2-fold higher concentrations compared to in vitro. Subsequently, histological sections of affected chorioallantoic membranes were stained with hematoxylin–eosin and alcian blue to determine the number and diameter of vessels as well as the thickness of the individual CAM layers (ectoderm, mesoderm, endoderm). Usnic acid was able to suppress the formation of VEGF- and bFGF-induced vessels with a diameter of less than 100 μm, which was demonstrated by the reduction of mesoderm thickness as well. Full article
(This article belongs to the Section Physiology and Pathology)
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10 pages, 4915 KiB  
Brief Report
Machine Learning Models for Identification and Prediction of Toxic Organic Compounds Using Daphnia magna Transcriptomic Profiles
by Tae-June Choi, Hyung-Eun An and Chang-Bae Kim
Life 2022, 12(9), 1443; https://doi.org/10.3390/life12091443 - 16 Sep 2022
Cited by 6 | Viewed by 2456
Abstract
A wide range of environmental factors heavily impact aquatic ecosystems, in turn, affecting human health. Toxic organic compounds resulting from anthropogenic activity are a source of pollution in aquatic ecosystems. To evaluate these contaminants, current approaches mainly rely on acute and chronic toxicity [...] Read more.
A wide range of environmental factors heavily impact aquatic ecosystems, in turn, affecting human health. Toxic organic compounds resulting from anthropogenic activity are a source of pollution in aquatic ecosystems. To evaluate these contaminants, current approaches mainly rely on acute and chronic toxicity tests, but cannot provide explicit insights into the causes of toxicity. As an alternative, genome-wide gene expression systems allow the identification of contaminants causing toxicity by monitoring the organisms’ response to toxic substances. In this study, we selected 22 toxic organic compounds, classified as pesticides, herbicides, or industrial chemicals, that induce environmental problems in aquatic ecosystems and affect human-health. To identify toxic organic compounds using gene expression data from Daphnia magna, we evaluated the performance of three machine learning based feature-ranking algorithms (Learning Vector Quantization, Random Forest, and Support Vector Machines with a Linear kernel), and nine classifiers (Linear Discriminant Analysis, Classification And Regression Trees, K-nearest neighbors, Support Vector Machines with a Linear kernel, Random Forest, Boosted C5.0, Gradient Boosting Machine, eXtreme Gradient Boosting with tree, and eXtreme Gradient Boosting with DART booster). Our analysis revealed that a combination of feature selection based on feature-ranking and a random forest classification algorithm had the best model performance, with an accuracy of 95.7%. This is a preliminary study to establish a model for the monitoring of aquatic toxic substances by machine learning. This model could be an effective tool to manage contaminants and toxic organic compounds in aquatic systems. Full article
(This article belongs to the Section Diversity and Ecology)
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17 pages, 511 KiB  
Review
Genomic Approaches to Uncovering the Coevolutionary History of Parasitic Lice
by Kevin P. Johnson
Life 2022, 12(9), 1442; https://doi.org/10.3390/life12091442 - 16 Sep 2022
Cited by 3 | Viewed by 2196
Abstract
Next-generation sequencing technologies are revolutionizing the fields of genomics, phylogenetics, and population genetics. These new genomic approaches have been extensively applied to a major group of parasites, the lice (Insecta: Phthiraptera) of birds and mammals. Two louse genomes have been assembled and annotated [...] Read more.
Next-generation sequencing technologies are revolutionizing the fields of genomics, phylogenetics, and population genetics. These new genomic approaches have been extensively applied to a major group of parasites, the lice (Insecta: Phthiraptera) of birds and mammals. Two louse genomes have been assembled and annotated to date, and these have opened up new resources for the study of louse biology. Whole genome sequencing has been used to assemble large phylogenomic datasets for lice, incorporating sequences of thousands of genes. These datasets have provided highly supported trees at all taxonomic levels, ranging from relationships among the major groups of lice to those among closely related species. Such approaches have also been applied at the population scale in lice, revealing patterns of population subdivision and inbreeding. Finally, whole genome sequence datasets can also be used for additional study beyond that of the louse nuclear genome, such as in the study of mitochondrial genome fragmentation or endosymbiont function. Full article
(This article belongs to the Special Issue Untangling Host-Symbiont Coevolutionary History in the High Throughput Sequencing (HTS) Era)
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16 pages, 3675 KiB  
Article
Comprehensive Transcriptome Analysis Reveals Sex-Specific Alternative Splicing Events in Zebrafish Gonads
by Xing Lin, Fei Liu, Kaifeng Meng, Hairong Liu, Yuanli Zhao, Yuanyuan Chen, Wei Hu and Daji Luo
Life 2022, 12(9), 1441; https://doi.org/10.3390/life12091441 - 16 Sep 2022
Cited by 2 | Viewed by 2619
Abstract
Alternative splicing is an important way of regulating gene functions in eukaryotes. Several key genes involved in sex determination and gonadal differentiation, such as nr5a1 and ddx4, have sex-biased transcripts between males and females, suggesting a potential regulatory role of alternative splicing [...] Read more.
Alternative splicing is an important way of regulating gene functions in eukaryotes. Several key genes involved in sex determination and gonadal differentiation, such as nr5a1 and ddx4, have sex-biased transcripts between males and females, suggesting a potential regulatory role of alternative splicing in gonads. Currently, the sex-specific alternative splicing events and genes have not been comprehensively studied at the genome-wide level in zebrafish. In this study, through global splicing analysis on three independent sets of RNA-seq data from matched zebrafish testes and ovaries, we identified 120 differentially spliced genes shared by the three datasets, most of which haven’t been reported before. Functional enrichment analysis showed that the GO terms of mRNA processing, mRNA metabolism and microtubule-based process were strongly enriched. The testis- and ovary-biased alternative splicing genes were identified, and part of them (tp53bp1, tpx2, mapre1a, kif2c, and ncoa5) were further validated by RT-PCR. Sequence characteristics analysis suggested that the lengths, GC contents, and splice site strengths of the alternative exons or introns may have different influences in different types of alternative splicing events. Interestingly, we identified an unexpected high proportion (over 70%) of non-frameshift exon-skipping events, suggesting that in these cases the two protein isoforms derived from alternative splicing may both have functions. Furthermore, as a representative example, we found that the alternative splicing of ncoa5 causes the loss of a conserved RRM domain in the short transcript predominantly produced in testes. Our study discovers novel sex-specific alternative splicing events and genes with high reliabilities in zebrafish testes and ovaries, which would provide attractive targets for follow-up studies to reveal the biological significances of alternative splicing events and genes in sex determination and gonadal differentiation. Full article
(This article belongs to the Special Issue Sex Determination and Gonad Development: From Mechanism to Application)
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22 pages, 1205 KiB  
Review
The Immune System as a Therapeutic Target for Alzheimer’s Disease
by Tarek Zieneldien, Janice Kim, Darrell Sawmiller and Chuanhai Cao
Life 2022, 12(9), 1440; https://doi.org/10.3390/life12091440 - 16 Sep 2022
Cited by 14 | Viewed by 3480
Abstract
Alzheimer’s disease (AD) is a heterogeneous neurodegenerative disorder and is the most common cause of dementia. Furthermore, aging is considered the most critical risk factor for AD. However, despite the vast amount of research and resources allocated to the understanding and development of [...] Read more.
Alzheimer’s disease (AD) is a heterogeneous neurodegenerative disorder and is the most common cause of dementia. Furthermore, aging is considered the most critical risk factor for AD. However, despite the vast amount of research and resources allocated to the understanding and development of AD treatments, setbacks have been more prominent than successes. Recent studies have shown that there is an intricate connection between the immune and central nervous systems, which can be imbalanced and thereby mediate neuroinflammation and AD. Thus, this review examines this connection and how it can be altered with AD. Recent developments in active and passive immunotherapy for AD are also discussed as well as suggestions for improving these therapies moving forward. Full article
(This article belongs to the Special Issue New Trends in Pharmaceutical Science)
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22 pages, 1100 KiB  
Review
MicroRNA: A Linking between Astrocyte Dysfunction, Mild Cognitive Impairment, and Neurodegenerative Diseases
by Angelica E. Ramírez, Natalia Gil-Jaramillo, María Alejandra Tapias, Yeimy González-Giraldo, Andrés Pinzón, Pedro J. Puentes-Rozo, Andrés Felipe Aristizábal-Pachón and Janneth González
Life 2022, 12(9), 1439; https://doi.org/10.3390/life12091439 - 16 Sep 2022
Cited by 7 | Viewed by 3401
Abstract
The importance of miRNAs in cellular processes and their dysregulation has taken significant importance in understanding different pathologies. Due to the constant increase in the prevalence of neurodegenerative diseases (ND) worldwide and their economic impact, mild cognitive impairment (MCI), considered a prodromal phase, [...] Read more.
The importance of miRNAs in cellular processes and their dysregulation has taken significant importance in understanding different pathologies. Due to the constant increase in the prevalence of neurodegenerative diseases (ND) worldwide and their economic impact, mild cognitive impairment (MCI), considered a prodromal phase, is a logical starting point to study this public health problem. Multiple studies have established the importance of miRNAs in MCI, including astrocyte regulation during stressful conditions. Additionally, the protection mechanisms exerted by astrocytes against some damage in the central nervous system (CNS) lead to astrocytic reactivation, in which a differential expression of miRNAs has been shown. Nevertheless, excessive reactivation can cause neurodegeneration, and a clear pattern defining the equilibrium point between a neuroprotective or detrimental astrocytic phenotype is unknown. Therefore, the miRNA expression has gained significant attention to understand the maintenance of brain balance and improve the diagnosis and treatment at earlier stages in the ND. Here, we provide a comprehensive review of the emerging role of miRNAs in cellular processes that contribute to the loss of cognitive function, including lipotoxicity, which can induce chronic inflammation, also considering the fundamental role of astrocytes in brain homeostasis. Full article
(This article belongs to the Special Issue Non-coding RNAs in Cellular Differentiation, Development, and Diseases)
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42 pages, 7386 KiB  
Review
Forces Driving a Magic Bullet to Its Target: Revisiting the Role of Thermodynamics in Drug Design, Development, and Optimization
by Conceição A. Minetti and David P. Remeta
Life 2022, 12(9), 1438; https://doi.org/10.3390/life12091438 - 15 Sep 2022
Cited by 5 | Viewed by 3456
Abstract
Drug discovery strategies have advanced significantly towards prioritizing target selectivity to achieve the longstanding goal of identifying “magic bullets” amongst thousands of chemical molecules screened for therapeutic efficacy. A myriad of emerging and existing health threats, including the SARS-CoV-2 pandemic, alarming increase in [...] Read more.
Drug discovery strategies have advanced significantly towards prioritizing target selectivity to achieve the longstanding goal of identifying “magic bullets” amongst thousands of chemical molecules screened for therapeutic efficacy. A myriad of emerging and existing health threats, including the SARS-CoV-2 pandemic, alarming increase in bacterial resistance, and potentially fatal chronic ailments, such as cancer, cardiovascular disease, and neurodegeneration, have incentivized the discovery of novel therapeutics in treatment regimens. The design, development, and optimization of lead compounds represent an arduous and time-consuming process that necessitates the assessment of specific criteria and metrics derived via multidisciplinary approaches incorporating functional, structural, and energetic properties. The present review focuses on specific methodologies and technologies aimed at advancing drug development with particular emphasis on the role of thermodynamics in elucidating the underlying forces governing ligand–target interaction selectivity and specificity. In the pursuit of novel therapeutics, isothermal titration calorimetry (ITC) has been utilized extensively over the past two decades to bolster drug discovery efforts, yielding information-rich thermodynamic binding signatures. A wealth of studies recognizes the need for mining thermodynamic databases to critically examine and evaluate prospective drug candidates on the basis of available metrics. The ultimate power and utility of thermodynamics within drug discovery strategies reside in the characterization and comparison of intrinsic binding signatures that facilitate the elucidation of structural–energetic correlations which assist in lead compound identification and optimization to improve overall therapeutic efficacy. Full article
(This article belongs to the Special Issue Biophysics of Nucleic Acids Celebrating the 75th Birthday of Professor Kenneth J. Breslauer)
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15 pages, 6210 KiB  
Article
The Role of MreB, MreC and MreD in the Morphology of the Diazotrophic Filament of Anabaena sp. PCC 7120
by Cristina Velázquez-Suárez, Ignacio Luque and Antonia Herrero
Life 2022, 12(9), 1437; https://doi.org/10.3390/life12091437 - 15 Sep 2022
Cited by 2 | Viewed by 2131
Abstract
The cyanobacterium Anabaena sp. PCC 7120 forms filaments of communicating cells. Under conditions of nitrogen scarcity, some cells differentiate into heterocysts, allowing the oxygen-sensitive N2-reduction system to be expressed and operated in oxic environments. The key to diazotrophic growth is the [...] Read more.
The cyanobacterium Anabaena sp. PCC 7120 forms filaments of communicating cells. Under conditions of nitrogen scarcity, some cells differentiate into heterocysts, allowing the oxygen-sensitive N2-reduction system to be expressed and operated in oxic environments. The key to diazotrophic growth is the exchange of molecules with nutritional and signaling functions between the two types of cells of the filament. During heterocyst differentiation, the peptidoglycan sacculus grows to allow cell enlargement, and the intercellular septa are rebuilt to narrow the contact surface with neighboring cells and to hold specific transport systems, including the septal junction complexes for intercellular molecular transfer, which traverse the periplasm between heterocysts and neighboring vegetative cells through peptidoglycan nanopores. Here we have followed the spatiotemporal pattern of peptidoglycan incorporation during heterocyst differentiation by Van-FL labeling and the localization and role of proteins MreB, MreC and MreD. We observed strong transitory incorporation of peptidoglycan in the periphery and septa of proheterocysts and a maintained focal activity in the center of mature septa. During differentiation, MreB, MreC and MreD localized throughout the cell periphery and at the cell poles. In mreB, mreC or mreD mutants, instances of strongly increased peripheral and septal peptidoglycan incorporation were detected, as were also heterocysts with aberrant polar morphology, even producing filament breakage, frequently lacking the septal protein SepJ. These results suggest a role of Mre proteins in the regulation of peptidoglycan growth and the formation of the heterocyst neck during differentiation, as well as in the maintenance of polar structures for intercellular communication in the mature heterocyst. Finally, as previously observed in filaments growing with combined nitrogen, in the vegetative cells of diazotrophic filaments, the lack of MreB, MreC or MreD led to altered localization of septal peptidoglycan-growth bands reproducing an altered localization of FtsZ and ZipN rings during cell division. Full article
(This article belongs to the Special Issue Molecular Genetics of Cyanobacteria)
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11 pages, 6298 KiB  
Article
H2O2/DEM-Promoted Maft Promoter Demethylation Drives Nrf2/ARE Activation in Zebrafish
by Ce Chen, Mingyue He, Xueting Li, Lidong Yu, Yi Liu, Yan Yang, Li Li, Jianbo Jia and Bingsheng Li
Life 2022, 12(9), 1436; https://doi.org/10.3390/life12091436 - 15 Sep 2022
Cited by 3 | Viewed by 2220
Abstract
The Nrf2/ARE signaling pathway is a cell survival response pathway in response to environmental stresses. The Nrf2/ARE signaling pathway can be activated by stimulating cysteine residues at different positions in the Keap1. However, the epigenetic mechanisms of the Nrf2/ARE pathway under different stimuli [...] Read more.
The Nrf2/ARE signaling pathway is a cell survival response pathway in response to environmental stresses. The Nrf2/ARE signaling pathway can be activated by stimulating cysteine residues at different positions in the Keap1. However, the epigenetic mechanisms of the Nrf2/ARE pathway under different stimuli are still poorly understood. In this study, we found that both hydrogen peroxide (H2O2) and Diethyl Maleate (DEM) activated the Nrf2/ARE signaling pathway at 120 hpf in zebrafish. H2O2 regulated the demethylation of the maft promoter by inhibiting the expression of methyltransferase. This promotes the mRNA expression of the Nrf2 binding factor maft, thereby promoting the downstream antioxidant genes. The methylation of the Nrf2/ARE signaling pathway was not significantly regulated by DEM. However, under oxidative stress, the methyltransferase inhibitors (decitabine and azacitidine) demethylated the promoter region of maft. It activated the expression of the maft, further improving the Nrf2/ARE signal pathway. At last, antioxidant target genes were activated. It was shown that H2O2 and DEM cooperated with methyltransferase inhibitors, providing an important reference for the treatment of oxidative stress-related diseases and breaking new ground for the study of the mechanism of methyltransferase inhibitors in the process of tumor chemotherapy. Full article
(This article belongs to the Topic Oxidative Stress and Inflammation)
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13 pages, 1553 KiB  
Article
Suppression of OCT-1 in Metastatic Breast Cancer Cells Reduces Tumor Metastatic Potential, Hypoxia Resistance, and Drug Resistance
by Alexander G. Stepchenko, Elizaveta V. Bulavkina, Tatiana N. Portseva, Sofia G. Georgieva and Elizaveta V. Pankratova
Life 2022, 12(9), 1435; https://doi.org/10.3390/life12091435 - 15 Sep 2022
Cited by 3 | Viewed by 2197
Abstract
OCT-1/POU2F1 is a ubiquitously expressed transcription factor. Its expression starts at the earliest stage of embryonic development. OCT-1 controls genes involved in the regulation of differentiation, proliferation, cell metabolism, and aging. High levels of OCT-1 transcription factor in tumor cells correlate with tumor [...] Read more.
OCT-1/POU2F1 is a ubiquitously expressed transcription factor. Its expression starts at the earliest stage of embryonic development. OCT-1 controls genes involved in the regulation of differentiation, proliferation, cell metabolism, and aging. High levels of OCT-1 transcription factor in tumor cells correlate with tumor malignancy and resistance to antitumor therapy. Here, we report that suppression of OCT-1 in breast cancer cells reduces their metastatic potential and drug resistance. OCT-1 knockdown in the MDA-MB231 breast cancer cells leads to a fivefold decrease (p < 0.01) in cell migration rates in the Boyden chamber. A decrease in the transcription levels of human invasion signature (HIS) genes (ARHGDIB, CAPZA2, PHACTR2, CDC42, XRCC5, and CAV1) has been also demonstrated by real-time PCR, with high expression of these genes being a hallmark of actively metastasizing breast cancer cells. Transcriptional activity of ATF6 response elements is significantly reduced in the cell lines with decreased OCT-1 expression, which results in lower levels of adaptive EPR stress response. OCT-1 knockdown more than two times increases the MDA-MB231 cell death rate in hypoxia and significantly increases the doxorubicin or docetaxel-treated MDA-MB231 cell death rate. Our findings indicate that OCT-1 may be an important therapeutic target and its selective inhibition may have significant therapeutic effects and may improve prognosis in breast cancer patients. Full article
(This article belongs to the Special Issue Genomic and Transcriptomic Alterations in Cancer and Aging)
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10 pages, 1641 KiB  
Article
Biological Potential of the Main Component, Thymoquinone, of Nigella sativa in Pulp Therapy—In Vitro Study
by Rana A. Alamoudi, Soha A. Alamoudi and Ruaa A. Alamoudi
Life 2022, 12(9), 1434; https://doi.org/10.3390/life12091434 - 15 Sep 2022
Cited by 4 | Viewed by 1892
Abstract
This work is designed to assess the antimicrobial efficacy, chelating efficacy, and dissolving capability of the bioactive agent of the Nigella sativa plant (thymoquinone). Four freeze-dried microorganisms were studied. Each species was treated with either 6% sodium Hypochlorite, thymoquinone, or sterile water. The [...] Read more.
This work is designed to assess the antimicrobial efficacy, chelating efficacy, and dissolving capability of the bioactive agent of the Nigella sativa plant (thymoquinone). Four freeze-dried microorganisms were studied. Each species was treated with either 6% sodium Hypochlorite, thymoquinone, or sterile water. The zone of inhibition was measured. Thirty extracted human premolar teeth were utilized to evaluate the smear layer removal. Root canals were mechanically instrumented and then irrigated with either 6% sodium Hypochlorite, 17% ethylenediaminetetraacetic acid, or thymoquinone for 1 min and scanned under the scanning electron microscopic to evaluate the cleanliness of the root canal and the remainder of the smear layer. To evaluate the tissue dissolving effect, Bovine Pulp Tissue was utilized. Randomly treated samples included: 6% sodium Hypochlorite, thymoquinone, or isotonic saline for 30 min. The remaining pulp tissue was weighed. Thymoquinone reported the highest inhibition of microbial multiplication compared to other irrigants (p < 0.001). Thymoquinone solution had an excellent antibacterial effect on endodontic pathogen and did not affect the inorganic and organic tissue inside the root canal. Meanwhile, it reported weak chelating and dissolving effects. Tissue dissolution was statistically significant with sodium Hypochlorite solution compared to other groups (p < 0.001). Full article
(This article belongs to the Special Issue Biological Activities of Natural Products, Antipsychotics, and Novel Derivatives - Volume II)
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2 pages, 164 KiB  
Editorial
New Paradigms in Pharmaceutical Development
by Ramón Cacabelos
Life 2022, 12(9), 1433; https://doi.org/10.3390/life12091433 - 15 Sep 2022
Cited by 1 | Viewed by 1526
Abstract
The main health problems in developed countries are cardiovascular diseases (25–30%), cancer (20–25%) and nervous system disorders (10–15%), which globally account for more than 80% of the morbidity and mortality in the general population [...] Full article
(This article belongs to the Special Issue New Trends in Pharmaceutical Science)
20 pages, 3795 KiB  
Article
Outcomes of Low-Temperature Stress on Biological Alterations within Pothos (Epipremnum aureum) Leaves
by Yanqing Wu, Xiang Cai and Yuhan Tang
Life 2022, 12(9), 1432; https://doi.org/10.3390/life12091432 - 14 Sep 2022
Cited by 5 | Viewed by 2786
Abstract
Pothos (Epipremnum aureum) is a commonly used indoor ornamental foliage, particularly in the middle and lower regions of the Yangtze River in China. It typically grows in the tropical area, and it is yet unclear whether prolonged winter temperatures cause plant [...] Read more.
Pothos (Epipremnum aureum) is a commonly used indoor ornamental foliage, particularly in the middle and lower regions of the Yangtze River in China. It typically grows in the tropical area, and it is yet unclear whether prolonged winter temperatures cause plant damage and impact its development. In this study, the E. aureum chilling injury response was explored by maintaining it at 1 °C. Based on the acquired results, low-temperature stress (LTS) induced wilting and yellowing of leaves and diminished chloroplast pigment concentrations, particularly the chlorophyll b content. LTS also induced overproduction of reactive oxygen species (ROS) within E. aureum and enhanced the relative electrical conductivity and superoxide dismutase activity. In addition, with prolonged LTS, the anatomical structure of E. aureum was severely damaged, resulting in a marked reduction in the photochemical activity of the photosystem Ⅱ reaction center and suppressed photosynthesis. Moreover, results of the transcriptomic analysis revealed that LTS induced the expression of genes involved in the α-linolenic acid metabolic pathway, plant hormone network, host plant–pathogen association, and MAPK axis, suggesting that LTS would activate its resistant response to cold stress. These results unraveled the physiological and transcriptomical response of E. aureum to chilling injury, which would lay a theoretical foundation for the cultivation of low-temperature-tolerant varieties of E. aureum. Full article
(This article belongs to the Special Issue Updates on Abiotic Stress Signaling and Response in Plants)
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20 pages, 1255 KiB  
Review
The Effects of Blue Light on Human Fibroblasts and Diabetic Wound Healing
by Meesha Purbhoo-Makan, Nicolette Nadene Houreld and Chukuka S. Enwemeka
Life 2022, 12(9), 1431; https://doi.org/10.3390/life12091431 - 14 Sep 2022
Cited by 9 | Viewed by 3787
Abstract
Diabetes is a serious threat to global health and is among the top 10 causes of death. The Diabetic foot ulcer (DFU) is among the most common and severe complications of the disease. Bacterial infections are common; therefore, timely aggressive management, using multidisciplinary [...] Read more.
Diabetes is a serious threat to global health and is among the top 10 causes of death. The Diabetic foot ulcer (DFU) is among the most common and severe complications of the disease. Bacterial infections are common; therefore, timely aggressive management, using multidisciplinary management approaches is needed to prevent complications, morbidity, and mortality, particularly in view of the growing cases of antibiotic-resistant bacteria. Photobiomodulation (PBM) involves the application of low-level light at specific wavelengths to induce cellular photochemical and photophysical responses. Red and near-infrared (NIR) wavelengths have been shown to be beneficial, and recent studies indicate that other wavelengths within the visible spectrum could be helpful as well, including blue light (400–500 nm). Reports of the antimicrobial activity and susceptibility of blue light on several strains of the same bacterium show that many bacteria are less likely to develop resistance to blue light treatment, meaning it is a viable alternative to antibiotic therapy. However, not all studies have shown positive results for wound healing and fibroblast proliferation. This paper presents a critical review of the literature concerning the use of PBM, with a focus on blue light, for tissue healing and diabetic ulcer care, identifies the pros and cons of PBM intervention, and recommends the potential role of PBM for diabetic ulcer care. Full article
(This article belongs to the Special Issue Blue Light and Wound Healing)
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20 pages, 2140 KiB  
Review
Artificial Intelligence in Biological Sciences
by Abhaya Bhardwaj, Shristi Kishore and Dhananjay K. Pandey
Life 2022, 12(9), 1430; https://doi.org/10.3390/life12091430 - 14 Sep 2022
Cited by 41 | Viewed by 14958
Abstract
Artificial intelligence (AI), currently a cutting-edge concept, has the potential to improve the quality of life of human beings. The fields of AI and biological research are becoming more intertwined, and methods for extracting and applying the information stored in live organisms are [...] Read more.
Artificial intelligence (AI), currently a cutting-edge concept, has the potential to improve the quality of life of human beings. The fields of AI and biological research are becoming more intertwined, and methods for extracting and applying the information stored in live organisms are constantly being refined. As the field of AI matures with more trained algorithms, the potential of its application in epidemiology, the study of host–pathogen interactions and drug designing widens. AI is now being applied in several fields of drug discovery, customized medicine, gene editing, radiography, image processing and medication management. More precise diagnosis and cost-effective treatment will be possible in the near future due to the application of AI-based technologies. In the field of agriculture, farmers have reduced waste, increased output and decreased the amount of time it takes to bring their goods to market due to the application of advanced AI-based approaches. Moreover, with the use of AI through machine learning (ML) and deep-learning-based smart programs, one can modify the metabolic pathways of living systems to obtain the best possible outputs with the minimal inputs. Such efforts can improve the industrial strains of microbial species to maximize the yield in the bio-based industrial setup. This article summarizes the potentials of AI and their application to several fields of biology, such as medicine, agriculture, and bio-based industry. Full article
(This article belongs to the Section Biochemistry, Biophysics and Computational Biology)
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12 pages, 2852 KiB  
Review
Origins of Life Research: The Conundrum between Laboratory and Field Simulations of Messy Environments
by David Deamer
Life 2022, 12(9), 1429; https://doi.org/10.3390/life12091429 - 14 Sep 2022
Cited by 7 | Viewed by 2790
Abstract
Most experimental results that guide research related to the origin of life are from laboratory simulations of the early Earth conditions. In the laboratory, emphasis is placed on the purity of reagents and carefully controlled conditions, so there is a natural tendency to [...] Read more.
Most experimental results that guide research related to the origin of life are from laboratory simulations of the early Earth conditions. In the laboratory, emphasis is placed on the purity of reagents and carefully controlled conditions, so there is a natural tendency to reject impurities and lack of control. However, life did not originate in laboratory conditions; therefore, we should take into consideration multiple factors that are likely to have contributed to the environmental complexity of the early Earth. This essay describes eight physical and biophysical factors that spontaneously resolve aqueous dispersions of ionic and organic solutes mixed with mineral particles and thereby promote specific chemical reactions required for life to begin. Full article
(This article belongs to the Special Issue Origin of Life in Chemically Complex Messy Environments)
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13 pages, 1713 KiB  
Article
Is There Any Improvement in Image Quality in Obese Patients When Using a New X-ray Tube and Deep Learning Image Reconstruction in Coronary Computed Tomography Angiography?
by Anne-Sofie Brunebjerg Pfeffer, Svea Deppe Mørup, Thomas Rueskov Andersen, Roda Abdulkadir Mohamed and Jess Lambrechtsen
Life 2022, 12(9), 1428; https://doi.org/10.3390/life12091428 - 13 Sep 2022
Cited by 2 | Viewed by 2091
Abstract
Deep learning image reconstruction (DLIR) is a technique that should reduce noise and improve image quality. This study assessed the impact of using both higher tube currents as well as DLIR on the image quality and diagnostic accuracy. The study consisted of 51 [...] Read more.
Deep learning image reconstruction (DLIR) is a technique that should reduce noise and improve image quality. This study assessed the impact of using both higher tube currents as well as DLIR on the image quality and diagnostic accuracy. The study consisted of 51 symptomatic obese (BMI > 30 kg/m2) patients with low to moderate risk of coronary artery disease (CAD). All patients underwent coronary computed tomography angiography (CCTA) twice, first with the Revolution CT scanner and then with the upgraded Revolution Apex scanner with the ability to increase tube current. Images were reconstructed using ASiR-V 50% and DLIR. The image quality was evaluated by an observer using a Likert score and by ROI measurements in aorta and the myocardium. Image quality was significantly improved with the Revolution Apex scanner and reconstruction with DLIR resulting in an odds ratio of 1.23 (p = 0.017), and noise was reduced by 41%. A total of 88% of the image sets performed with Revolution Apex + DLIR were assessed as good enough for diagnosis compared to 69% of the image sets performed with Revolution Apex/CT + ASiR-V. In obese patients, the combination of higher tube current and DLIR significantly improves the subjective image quality and diagnostic utility and reduces noise. Full article
(This article belongs to the Collection Advances in Coronary Heart Disease)
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