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Life, Volume 10, Issue 10 (October 2020) – 32 articles

Cover Story (view full-size image): Cannabigerol (CBG) and Cannabidiol (CBD), extracted from Cannabis sativa, are the two most studied non-psychoactive cannabinoids. Even if the effects of CBD have already been studied, very little is known about the properties of CBG. Transcriptomic analysis performed through next-generation sequencing (NGS) technology allowed us to evaluate how CBG (1 or 5 µM) and CBD (1 or 5 µM) modulate, in NSC-34 motor neuron-like cells, the genes involved in the excitatory glutamate, inhibitory γ-aminobutyric acid (GABA), and dopamine signaling pathways. It is interesting to observe that the different doses of CBG modulate the transcriptomic profile similarly to CBD. Furthermore, neither CBD nor CBD are cytotoxic and both decrease the expression levels of pro-apoptotic genes. View this paper
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17 pages, 2821 KiB  
Article
Novel Methylation Patterns Predict Outcome in Uveal Melanoma
by Sarah Tadhg Ferrier and Julia Valdemarin Burnier
Life 2020, 10(10), 248; https://doi.org/10.3390/life10100248 - 20 Oct 2020
Cited by 6 | Viewed by 2378
Abstract
Uveal melanoma (UM) is the most common intraocular tumor in adults. Despite effective local treatments, 50% of patients develop metastasis. Better ways to determine prognosis are needed as well as new therapeutic targets. Epigenetic changes are important events driving cancer progression; however, few [...] Read more.
Uveal melanoma (UM) is the most common intraocular tumor in adults. Despite effective local treatments, 50% of patients develop metastasis. Better ways to determine prognosis are needed as well as new therapeutic targets. Epigenetic changes are important events driving cancer progression; however, few studies exist on methylation changes in UM. Our aim was to identify methylation events associated with UM prognosis. Matched clinical, genetic, and methylation data for 80 UM cases were obtained from The Cancer Genome Atlas (TCGA). Top differentially methylated loci were sorted through hierarchical clustering based on methylation patterns, and these patterns were compared to tumor characteristics, genomic aberrations, and patient outcome. Hierarchical clustering revealed two distinct groups. These classifications effectively separated high and low-risk cases, with significant differences between groups in patient survival (p < 0.0001) and correlation with known prognostic factors. Major differences in methylation of specific genes, notably NFIA, HDAC4, and IL12RB2, were also seen. The methylation patterns identified in this study indicate potential novel prognostic indicators of UM and highlight the power of methylation changes in predicting outcome. The methylation events enriched in the high-risk group suggest that epigenetic modulating drugs may be useful in reducing metastatic potential, and that specific differentially methylated loci could act as biomarkers of therapeutic response. Full article
(This article belongs to the Special Issue Melanoma: Dark Tumor with Little Light for Metastasis Treatment)
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19 pages, 2945 KiB  
Article
Right Heart Changes Impact on Clinical Phenotype of Amyloid Cardiac Involvement: A Single Centre Study
by Sebastiano Cicco, Antonio Giovanni Solimando, Roberta Buono, Nicola Susca, Gianfranco Inglese, Assunta Melaccio, Marcella Prete, Roberto Ria, Vito Racanelli and Angelo Vacca
Life 2020, 10(10), 247; https://doi.org/10.3390/life10100247 - 18 Oct 2020
Cited by 8 | Viewed by 2444
Abstract
Amyloidosis is due to deposition of an excessive amount of protein in many parenchymal tissues, including myocardium. The onset of cardiac Amyloidosis (CA) is an inauspicious prognostic factor, which can lead to sudden death. We retrospectively analyzed 135 patients with systemic amyloidosis, admitted [...] Read more.
Amyloidosis is due to deposition of an excessive amount of protein in many parenchymal tissues, including myocardium. The onset of cardiac Amyloidosis (CA) is an inauspicious prognostic factor, which can lead to sudden death. We retrospectively analyzed 135 patients with systemic amyloidosis, admitted to our ward between 1981 and 2019. Among them, 54 patients (46.30% F/53.70% M, aged 63.95 ± 12.82) presented CA at baseline. In 53 patients, it was associated with a multiorgan involvement, while in one there was a primary myocardial deposition. As a control group, we enrolled 81 patients (49.30% F/50.70% M, aged 58.33 ± 15.65) who did not meet the criteria for CA. In 44/54 of patients CA was associated with AL, 5/54 with AA and 3/54 of patients with ATTR, and in 1/54 AL was related to hemodialysis and in 1/54 to Gel-Amyloidosis. The most common AL type was IgG (28/44); less frequent forms were either IgA (7/44) or IgD (2/44), while seven patients had a λ free light chain form. The 32 AL with complete Ig were 31 λ-chain and just one k-chain. CA patients presented normal BP (SBP 118.0 ± 8.4 mmHg; DBP 73.8 ± 4.9 mmHg), while those with nCA had an increased proteinuria (p = 0.02). TnI and NT-proBNP were significantly increased compared to nCA (p = 0.031 and p = 0.047, respectively). In CA patients we found an increased LDH compared to nCA (p = 0.0011). CA patients were also found to have an increased interventricular septum thickness compared to nCA (p = 0.002), a decreased Ejection Fraction % (p = 0.0018) and Doppler velocity E/e’ ratio (p = 0.0095). Moreover, CA patients had an enhanced right atrium area (p = 0.0179), right ventricle basal diameter (p = 0.0112) and wall thickness (p = 0.0471) compared to nCA, and an increased inferior cava vein diameter (p = 0.0495) as well. TAPSE was the method chosen to evaluate systolic function of the right heart. In CA subjects very poor TAPSE levels were found compared to nCA patients (p = 0.0495). Additionally, we found a significant positive correlation between TAPSE and lymphocyte count (r = 0.47; p = 0.031) as well as Gamma globulins (r = 0.43, p = 0.033), Monoclonal components (r = 0.72; p = 0.047) and IgG values (r = 0.62, p = 0.018). Conversely, a significant negative correlation with LDH (r = −0.57, p = 0.005), IVS (r = −0.51, p = 0.008) and diastolic function evaluated as E/e’ (r = −0.60, p = 0.003) were verified. CA patients had very poor survival rates compared to controls (30 vs. 66 months in CA vs. nCA, respectively, p = 0.15). Mean survival of CA individuals was worse also when stratified according to NT-proBNP levels, using 2500 pg/mL as class boundary (174 vs. 5.5 months, for patients with lower vs. higher values than the median, respectively p = 0.013). In much the same way, a decreased right heart systolic function was correlated with a worse prognosis (18.0 months median survival, not reached in subjects with lower values than 18 mm, p = 0.0186). Finally, our data highlight the potential prognostic and predictive value of right heart alterations characterizing amyloidosis, as a novel clinical parameter correlated to increased LDH and immunoglobulins levels. Overall, we confirm the clinical relevance of cardiac involvement suggests that right heart evaluation may be considered as a new marker for clinical risk stratification in patients with amyloidosis. Full article
(This article belongs to the Special Issue Amyloids, Prions, and Related Phenomena)
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16 pages, 4777 KiB  
Article
Alterations of Specific Lymphocytic Subsets with Aging and Age-Related Metabolic and Cardiovascular Diseases
by Ying Jen Chen, Yi Jen Liao, Van Thi Ngoc Tram, Chung Hao Lin, Kuo Chen Liao and Chao Lien Liu
Life 2020, 10(10), 246; https://doi.org/10.3390/life10100246 - 17 Oct 2020
Cited by 6 | Viewed by 1882
Abstract
To investigate the association of immunosenescence with aged-related morbidity in the elderly, a clinical study was conducted to analyze and compare the alterations in peripheral blood (PB) T-cell subsets among young healthy (YH) controls, elderly healthy (EH) controls, and age-matched elderly patients with [...] Read more.
To investigate the association of immunosenescence with aged-related morbidity in the elderly, a clinical study was conducted to analyze and compare the alterations in peripheral blood (PB) T-cell subsets among young healthy (YH) controls, elderly healthy (EH) controls, and age-matched elderly patients with metabolic diseases (E-MDs), with cardiovascular diseases (E-CVDs) or with both (E-MDs/E-CVDs). The frequencies of CD3T, CD8T and invariant natural killer T (iNKT) cells were decreased in the EH, E-MD and E-CVD cohorts, indicating a decline in defense function. Although CD4T and regulatory T (Treg) cell frequencies tended to increase with aging, they were lower in patients with E-MDs and E-CVDs. Subset analyses of T-cells consistently showed the accumulation of senescent T-cell in aging and in patients with E-MDs and E-CVDs, compared with YH volunteers. These accumulated senescent T-cells were undergoing apoptosis upon stimulation due to the replicative senescence stage of T-cells. In addition, serum levels of cytokines, including interferon (IF)-γ, transforming growth factor (TGF)-β and growth differentiation factor (GDF)-15, consistently reflected alterations in T-cell subsets. This study demonstrated that T-cell subset changes with paralleled alterations in cytokines were associated with aging and age-related pathogenesis. These altered T-cell subsets and/or cytokines can potentially serve as biomarkers for the prevention, diagnosis and treatment of age-related morbidities. Full article
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17 pages, 1365 KiB  
Article
Deregulated Serotonin Pathway in Women with Morbid Obesity and NAFLD
by Jessica Binetti, Laia Bertran, David Riesco, Carmen Aguilar, Salomé Martínez, Fàtima Sabench, Jose Antonio Porras, Javier Camaron, Daniel Del Castillo, Cristóbal Richart and Teresa Auguet
Life 2020, 10(10), 245; https://doi.org/10.3390/life10100245 - 16 Oct 2020
Cited by 11 | Viewed by 2669
Abstract
Non-alcoholic fatty liver disease (NAFLD) extends from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH). Peripheral serotonin (5-HT) has become as an important regulator of different metabolic pathways. 5-HT has been related to obesity and lipid accumulation in the liver. The objective of this [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) extends from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH). Peripheral serotonin (5-HT) has become as an important regulator of different metabolic pathways. 5-HT has been related to obesity and lipid accumulation in the liver. The objective of this study was to assess the relationship between the 5-HT signaling pathway and the degree of NAFLD, as well as to investigate whether peripheral 5-HT levels are related to the hepatic and jejunal mRNA abundance of serotonin receptors (HTR) in a cohort of women with morbid obesity (MO) and NAFLD. ELISA was used to quantify the serum 5-HT from normal-weight subjects (n = 26) and patients with MO (n = 58). We used RTq-PCR analysis to evaluate the relative expression of HTR in women with MO with normal liver (n = 22), SS (n = 21), and NASH (n = 15). The 5-HT was diminished in women with MO under a hypocaloric diet, regardless of the presence of NAFLD. Additionally, we report a negative correlation of 5-HT levels with metabolic syndrome criteria, suggesting that serotonin may have a protective role in obesity. Additionally, the hepatic expression of HTR2A and HTR2B were decreased in women with MO and NAFLD, but no significant differences in the HTR jejunal expression according to the presence of NAFLD were found. Full article
(This article belongs to the Special Issue Fatty Liver Syndrome)
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18 pages, 1986 KiB  
Review
Is Malignant Potential of Barrett’s Esophagus Predictable by Endoscopy Findings?
by Yuji Amano, Norihisa Ishimura and Shunji Ishihara
Life 2020, 10(10), 244; https://doi.org/10.3390/life10100244 - 16 Oct 2020
Cited by 2 | Viewed by 5730
Abstract
Given that endoscopic findings can be used to predict the potential of neoplastic progression in Barrett’s esophagus (BE) cases, the detection rate of dysplastic Barrett’s lesions may become higher even in laborious endoscopic surveillance because a special attention is consequently paid. However, endoscopic [...] Read more.
Given that endoscopic findings can be used to predict the potential of neoplastic progression in Barrett’s esophagus (BE) cases, the detection rate of dysplastic Barrett’s lesions may become higher even in laborious endoscopic surveillance because a special attention is consequently paid. However, endoscopic findings for effective detection of the risk of neoplastic progression to esophageal adenocarcinoma (EAC) have not been confirmed, though some typical appearances are suggestive. In the present review, endoscopic findings that can be used predict malignant potential to EAC in BE cases are discussed. Conventional results obtained with white light endoscopy, such as length of BE, presence of esophagitis, ulceration, hiatal hernia, and nodularity, are used as indicators of a higher risk of neoplastic progression. However, there are controversies in some of those findings. Absence of palisade vessels may be also a new candidate predictor, as that reveals degree of intense inflammation and of cyclooxygenase-2 protein expression with accelerated cellular proliferation. Furthermore, an open type of mucosal pattern and enriched stromal blood vessels, which can be observed by image-enhanced endoscopy, including narrow band imaging, have been confirmed as factors useful for prediction of neoplastic progression of BE because they indicate more frequent cyclooxygenase-2 protein expression along with accelerated cellular proliferation. Should the malignant potential of BE be shown predictable by these endoscopic findings, that would simplify methods used for an effective surveillance, because patients requiring careful monitoring would be more easily identified. Development in the near future of a comprehensive scoring system for BE based on clinical factors, biomarkers and endoscopic predictors is required. Full article
(This article belongs to the Section Medical Research)
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9 pages, 2063 KiB  
Article
Quercitrin Ameliorates Hyperlipidemia and Hepatic Steatosis in Ovariectomized Mice
by Haeng Jeon Hur, Yeon-Hui Jeong, Sang Hee Lee and Mi Jeong Sung
Life 2020, 10(10), 243; https://doi.org/10.3390/life10100243 - 15 Oct 2020
Cited by 14 | Viewed by 2629
Abstract
Nonalcoholic fatty liver disease (NAFLD) is associated with progressive metabolic diseases. Estrogen deficiency increases the NAFLD risk among postmenopausal women. Thus, effective agents to prevent and treat NAFLD in postmenopausal women are required. Quercitrin (Quer) is a natural glycosylated flavonoid with antimicrobial, anti-inflammatory, [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is associated with progressive metabolic diseases. Estrogen deficiency increases the NAFLD risk among postmenopausal women. Thus, effective agents to prevent and treat NAFLD in postmenopausal women are required. Quercitrin (Quer) is a natural glycosylated flavonoid with antimicrobial, anti-inflammatory, and hypolipidemic effects. This study investigated whether Quer improves dysregulated lipid metabolism and suppresses hepatic steatosis in ovariectomized (OVX) mice as an experimental model mimicking postmenopausal women. Mice were assigned to the following four groups: SHAM, OVX, OVX + β-estradiol (0.4 mg/kg diet), and OVX + Quer (500 mg/kg diet). Mice were administered a diet with or without Quer for three months. OVX mice displayed significantly higher body mass, epidermal fat, and liver weights than those of SHAM mice. However, these levels were reduced in Quer-treated mice. Quer treatment reduced the levels of serum lipid metabolites, including triglycerides, total cholesterol, and low-density lipoprotein cholesterol. Furthermore, Quer reduced liver lipid steatosis and inhibited the expression of proinflammatory cytokines, such as tumor necrosis factor-α, IL-6, and IL-1β. The results of the present study indicate that Quer improves dysregulated lipid metabolism and reduces hepatic steatosis and inflammation by compensating for estrogen deficiency, suggesting that Quer may potentially exert protective effects during hepatic steatosis in postmenopausal women. Full article
(This article belongs to the Section Plant Science)
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18 pages, 264 KiB  
Article
Clinical Evaluation of a Custom Gene Panel as a Tool for Precision Male Infertility Diagnosis by Next-Generation Sequencing
by Rossella Cannarella, Vincenza Precone, Giulia Guerri, Gian Maria Busetto, Gian Carlo Di Renzo, Sandro Gerli, Elena Manara, Astrit Dautaj, Matteo Bertelli and Aldo Eugenio Calogero
Life 2020, 10(10), 242; https://doi.org/10.3390/life10100242 - 15 Oct 2020
Cited by 12 | Viewed by 2744
Abstract
Background: Up to 15% of couples are infertile and male factor infertility accounts for approximately 50% of these cases. Male infertility is a multifactorial pathological condition. The genetic of male infertility is very complex and at least 2000 genes are involved in its [...] Read more.
Background: Up to 15% of couples are infertile and male factor infertility accounts for approximately 50% of these cases. Male infertility is a multifactorial pathological condition. The genetic of male infertility is very complex and at least 2000 genes are involved in its etiology. Genetic testing by next-generation sequencing (NGS) technologies can be relevant for its diagnostic value in male infertile patients. Therefore, the aim of this study was to implement the diagnostic offer with the use of an NGS panel for the identification of genetic variants. Methods: We developed an NGS gene panel that we used in 22 male infertile patients. The panel consisted of 110 genes exploring the genetic causes of male infertility; namely spermatogenesis failure due to single-gene mutations, central hypogonadism, androgen insensitivity syndrome, congenital hypopituitarism, and primary ciliary dyskinesia. Results: NGS and a subsequent sequencing of the positive pathogenic or likely pathogenic variants, 5 patients (23%) were found to have a molecular defect. In particular, pathogenic variants were identified in TEX11, CCDC39, CHD7, and NR5A1 genes. Moreover, 14 variants of unknown significance and 7 novel variants were found that require further functional studies and family segregation. Conclusion: This extended NGS-based diagnostic approach may represent a useful tool for the diagnosis of male infertility. The development of a custom-made gene panel by NGS seems capable of reducing the proportion of male idiopathic infertility. Full article
(This article belongs to the Special Issue The Increasing Role of Next Generation Sequencing Methods in Mutation Analysis)
16 pages, 776 KiB  
Article
Non-Criteria Antiphospholipid Antibodies: Risk Factors for Endothelial Dysfunction in Women with Pre-Eclampsia
by Lara Belmar Vega, Gema Fernández Fresnedo, Juan Irure Ventura, Victoria Orallo Toural, Milagros Heras Vicario, Juan Carlos Ruiz San Millán, Emilio Rodrigo and Marcos López Hoyos
Life 2020, 10(10), 241; https://doi.org/10.3390/life10100241 - 14 Oct 2020
Cited by 4 | Viewed by 2294
Abstract
The association between unconventional antiphospholipid antibodies and pre-eclampsia in patients without thrombotic manifestations and its relationship with endothelial dysfunction after delivery has been studied poorly. We included 157 pregnant women, 122 of them having developed pre-eclampsia (56 non-severe and 66 severe). The determination [...] Read more.
The association between unconventional antiphospholipid antibodies and pre-eclampsia in patients without thrombotic manifestations and its relationship with endothelial dysfunction after delivery has been studied poorly. We included 157 pregnant women, 122 of them having developed pre-eclampsia (56 non-severe and 66 severe). The determination of classical and unconventional, as well as pulse wave velocity and ankle-brachial index were performed at three months after delivery. The prevalence of unconventional antiphospholipid antibodies was 22.9% and 54.9% in patients included in control and pre-eclampsia groups, respectively (p = 0.001). The most frequent antiphospholipid antibody was IgM anti-phosphatidylserine/prothrombin in both cohorts. The presence of IgM anti-phosphatidylserine/prothrombin showed an association with the development of pre-eclampsia (OR = 5.4; CI 95% (2.0–14.9), p = 0.001) with an AUC of 0.744 (p < 0.001). Likewise, IgM anti-phosphatidylserine/prothrombin exhibited a positive linear correlation with pulse wave velocity values (rho = 0.830; p < 0.001) and an association with the presence of pulse wave velocity altered values (OR = 1.33; CI95% (1.10–1.59), p = 0.002). With regard to ankle braquial index values, the presence of IgM anti-phosphatidylserine/prothrombin displayed a weak negative correlation (rho = −0.466; p < 0.001) and an association with altered ankle braquial index values (OR = 1.08; CI 95% (1.04–1.13), p < 0.001). In patients who developed preeclampsia, the presence of IgM anti-phosphatidylserine/prothrombin could be associated with endothelial dysfunction, causing alteration of cardiovascular parameters. Full article
(This article belongs to the Special Issue Reproductive Health Concerns for Women)
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15 pages, 4936 KiB  
Article
Electroacupuncture on the Scalp over the Motor Cortex Ameliorates Behavioral Deficits Following Neonatal Hypoxia-Ischemia in Rats via the Activation of Neural Stem Cells
by Da Hee Jung, Malk Eun Pak, Hong Ju Lee, Sung Min Ahn, Young Ju Yun, Yong-Il Shin, Hwa Kyoung Shin, Seo-Yeon Lee and Byung Tae Choi
Life 2020, 10(10), 240; https://doi.org/10.3390/life10100240 - 14 Oct 2020
Cited by 1 | Viewed by 2261
Abstract
Electroacupuncture (EA) therapy via alternating current stimulation on the scalp over the motor cortex is used for the treatment of brain disorders. Perinatal hypoxia-ischemia (HI), a brain injury in newborns, leads to long-term neurologic complications. Here, we investigated whether EA could promote functional [...] Read more.
Electroacupuncture (EA) therapy via alternating current stimulation on the scalp over the motor cortex is used for the treatment of brain disorders. Perinatal hypoxia-ischemia (HI), a brain injury in newborns, leads to long-term neurologic complications. Here, we investigated whether EA could promote functional improvements and neurogenesis in a neonatal HI rat model. A neonatal HI rat model was induced by permanent ligation of the left carotid artery in postnatal day 7 pups. EA for neonatal HI rats was performed at 2 Hz (1, 3, or 5 mA; 20 min) from 4–6 weeks after birth. HI rats undergoing EA had improved motor and memory function, with the greatest improvement after 3 mA EA. The corpus callosum was significantly thicker and showed a significant increase in proliferating astrocytes in the 3 mA EA group. We observed proliferating cells and a greater number of newly developed neurons and astrocytes in the subventricular zone and dentate gyrus of the 3 mA EA group than in those of the HI group. These results suggest that EA promotes functional improvements following neonatal HI assault via the proliferation and differentiation of neural stem cells. This effect was the strongest after 3 mA EA, suggesting that this is the optimal treatment dose. Full article
(This article belongs to the Special Issue Stem Cells Therapy)
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10 pages, 1281 KiB  
Article
Markers of Endothelial Injury and Dysfunction in Early- and Late-Onset Preeclampsia
by Jakub Kornacki, Przemysław Wirstlein and Ewa Wender-Ozegowska
Life 2020, 10(10), 239; https://doi.org/10.3390/life10100239 - 14 Oct 2020
Cited by 12 | Viewed by 1832
Abstract
With regard to differences in the clinical symptoms of preeclampsia (PE), the degree of endothelial dysfunction may differ between early and late-onset preeclampsia (EOP and LOP). The authors of this study examined it by assessing the endothelial injury level in women with EOP [...] Read more.
With regard to differences in the clinical symptoms of preeclampsia (PE), the degree of endothelial dysfunction may differ between early and late-onset preeclampsia (EOP and LOP). The authors of this study examined it by assessing the endothelial injury level in women with EOP (20 patients) and LOP (20 patients) and in normotensive pregnant women (20 patients) in their late second and third trimesters of pregnancy, using the two markers—the serum concentration of hyaluronan (HA) and the serum level of soluble vascular cell adhesion molecule-1 (sVCAM-1). The serum concentrations of HA and sVCAM-1 did not differ significantly between the EOP and LOP patients. However, these were statistically higher than that of the control group participants (p < 0.05; p < 0.001). A significant correlation between the levels of HA and sVCAM-1 was found both in the entire group of patients with preeclampsia (p = 0.0277) and in women with late-onset disease (p = 0.0364), but not in the patients with early-onset preeclampsia (p = 0.331). The obtained results indicated a comparable level of endothelial injury in the two types of PE. The presence of a similar degree of endothelial injury in patients with EOP and LOP should create awareness among all clinicians about the possible fatal complications in both groups of patients with PE. Full article
(This article belongs to the Special Issue Reproductive Health Concerns for Women)
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16 pages, 2227 KiB  
Article
Multiple Non-Species-Specific Pathogens Possibly Triggered the Mass Mortality in Pinna nobilis
by Fabio Scarpa, Daria Sanna, Ilenia Azzena, Davide Mugetti, Francesco Cerruti, Sepideh Hosseini, Piero Cossu, Stefania Pinna, Daniele Grech, David Cabana, Viviana Pasquini, Giuseppe Esposito, Nicoletta Cadoni, Fabrizio Atzori, Elisabetta Antuofermo, Piero Addis, Leonardo Antonio Sechi, Marino Prearo, Simone Peletto, Marianna A. Mossa, Tiziana Saba, Vittorio Gazale and Marco Casuadd Show full author list remove Hide full author list
Life 2020, 10(10), 238; https://doi.org/10.3390/life10100238 - 13 Oct 2020
Cited by 31 | Viewed by 4824
Abstract
The fan mussel, Pinna nobilis, represents the largest bivalve endemic to the Mediterranean Sea. Since 2016, dramatic mass mortality of this species has been observed in several areas. The first surveys suggested that Haplosporidium pinnae (currently considered species-specific) was the main etiological [...] Read more.
The fan mussel, Pinna nobilis, represents the largest bivalve endemic to the Mediterranean Sea. Since 2016, dramatic mass mortality of this species has been observed in several areas. The first surveys suggested that Haplosporidium pinnae (currently considered species-specific) was the main etiological agent, but recent studies have indicated that a multifactorial disease may be responsible for this phenomenon. In this study, we performed molecular diagnostic analyses on P. nobilis, P. rudis, and bivalve heterologous host species from the island of Sardinia to shed further light on the pathogens involved in the mass mortality. The results support the occurrence of a multifactorial disease and that Mycobacterium spp. and H. pinnae are not necessarily associated with the illness. Indeed, our analyses revealed that H. pinnae is not species-specific for P. nobilis, as it was present in other bivalves at least three years before the mass mortality began, and species of Mycobacterium were also found in healthy individuals of P. nobilis and P. rudis. We also detected the species Rhodococcus erythropolis, representing the first report in fan mussels of a bacterium other than Mycobacterium spp. and Vibrio spp. These results depict a complicated scenario, further demonstrating how the P. nobilis mass mortality event is far from being fully understood. Full article
(This article belongs to the Section Evolutionary Biology)
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9 pages, 234 KiB  
Article
Premature Adrenarche in Children with Prader-Willi Syndrome Treated with Recombinant Human Growth Hormone Seems to Not Influence the Course of Central Puberty and the Efficacy and Safety of the Therapy
by Agnieszka Lecka-Ambroziak, Marta Wysocka-Mincewicz, Kamila Marszałek-Dziuba, Agnieszka Rudzka-Kocjan and Mieczysław Szalecki
Life 2020, 10(10), 237; https://doi.org/10.3390/life10100237 - 10 Oct 2020
Cited by 7 | Viewed by 1966
Abstract
Puberty in children with Prader-Willi syndrome (PWS) is usually delayed and/or incomplete but in some patients premature/early adrenarche is observed. We assessed the premature adrenarche (PA) in PWS patients during the recombinant human growth hormone (rhGH) therapy and influence of PA on the [...] Read more.
Puberty in children with Prader-Willi syndrome (PWS) is usually delayed and/or incomplete but in some patients premature/early adrenarche is observed. We assessed the premature adrenarche (PA) in PWS patients during the recombinant human growth hormone (rhGH) therapy and influence of PA on the course of central puberty (CP), rhGH efficacy and safety, and patients’ metabolic state. Forty-nine PWS patients were treated with rhGH, 11 presented with PA (group 1) and 14 had normal course of adrenarche (group 2). PA was observed in 22.5% of the PWS children treated with rhGH. The mean time between the rhGH start and the adrenarche, the rhGH dose, the growth velocity and the insulin-like growth factor 1 SD (IGF1 SD) during the treatment, as well as the time of CP, final height SD and BMI SD were similar in both groups. There were also no significant differences in the metabolic assessment—the oral glucose tolerance test (OGTT) and lipid profile results. PA may be a part of the clinical picture of PWS, apart from hypogonadotrophic hypogonadism and it seems to have no influence on CP in PWS patients. The rhGH efficacy and safety were comparable in the patients with PA and the normal course of adrenarche. Full article
(This article belongs to the Section Medical Research)
11 pages, 249 KiB  
Article
Oral Dysplastic Complications after HSCT: Single Case Series of Multidisciplinary Evaluation of 80 Patients
by Stefania Leuci, Noemi Coppola, Andrea Blasi, Elvira Ruoppo, Maria Eleonora Bizzoca, Lorenzo Lo Muzio, Luana Marano, Antonio Maria Risitano and Michele Davide Mignogna
Life 2020, 10(10), 236; https://doi.org/10.3390/life10100236 - 09 Oct 2020
Cited by 8 | Viewed by 1755
Abstract
Oral squamous cell carcinoma (OSCC) is the most common secondary solid malignancy after hematopoietic stem-cell transplantation (HSCT). OSCC following HSCT is frequently preceded by chronic graft-versus-host disease (cGVHD). The aim of this study was to describe a cohort of post-HSCT patients and to [...] Read more.
Oral squamous cell carcinoma (OSCC) is the most common secondary solid malignancy after hematopoietic stem-cell transplantation (HSCT). OSCC following HSCT is frequently preceded by chronic graft-versus-host disease (cGVHD). The aim of this study was to describe a cohort of post-HSCT patients and to evaluate the onset of oral epithelial dysplasia and/or OSCC over time. In this retrospective cohort study, we present a cohort of hematological patients that underwent HSCT. Demographic variables, clinical hematological data, data regarding acute graft-versus-host disease (aGVHD) and cGVHD, and oral clinical features were analyzed. We focused on clinicopathological features of a subgroup of 22 patients with oral cGVHD and OSCC after HSCT. Among 80 included patients, 46 patients (57.5%) developed aGVHD and 39 patients (48.7%) developed cGVHD. Oral mucosa was involved in 17 patients with aGVHD (36.9%) and in 22 patients (56.4%) with cGVHD. Out of a total of 22 oral biopsies, roughly 40% revealed mild to moderate dysplasia, and 32% were OSCC. In the absence of international agreement on the best timing of oral follow-up after HSCT, it is mandatory to establish a close multidisciplinary evaluation in order to prevent the onset of HSCT-related OSCC and to reduce post-transplant mortality due to secondary tumors. Full article
(This article belongs to the Special Issue Oral Cancer—Diagnosis and Therapeutics 2020)
22 pages, 1513 KiB  
Review
Approaching Gravity as a Continuum Using the Rat Partial Weight-Bearing Model
by Marie Mortreux and Megan E. Rosa-Caldwell
Life 2020, 10(10), 235; https://doi.org/10.3390/life10100235 - 08 Oct 2020
Cited by 9 | Viewed by 4080
Abstract
For decades, scientists have relied on animals to understand the risks and consequences of space travel. Animals remain key to study the physiological alterations during spaceflight and provide crucial information about microgravity-induced changes. While spaceflights may appear common, they remain costly and, coupled [...] Read more.
For decades, scientists have relied on animals to understand the risks and consequences of space travel. Animals remain key to study the physiological alterations during spaceflight and provide crucial information about microgravity-induced changes. While spaceflights may appear common, they remain costly and, coupled with limited cargo areas, do not allow for large sample sizes onboard. In 1979, a model of hindlimb unloading (HU) was successfully created to mimic microgravity and has been used extensively since its creation. Four decades later, the first model of mouse partial weight-bearing (PWB) was developed, aiming at mimicking partial gravity environments. Return to the Lunar surface for astronauts is now imminent and prompted the need for an animal model closer to human physiology; hence in 2018, our laboratory created a new model of PWB for adult rats. In this review, we will focus on the rat model of PWB, from its conception to the current state of knowledge. Additionally, we will address how this new model, used in conjunction with HU, will help implement new paradigms allowing scientists to anticipate the physiological alterations and needs of astronauts. Finally, we will discuss the outstanding questions and future perspectives in space research and propose potential solutions using the rat PWB model. Full article
(This article belongs to the Collection Space Life Sciences)
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15 pages, 2684 KiB  
Article
Biochemical Characterization of a Bifunctional Enzyme Constructed by the Fusion of a Glucuronan Lyase and a Chitinase from Trichoderma sp.
by Zeineb Baklouti, Cédric Delattre, Guillaume Pierre, Christine Gardarin, Slim Abdelkafi, Philippe Michaud and Pascal Dubessay
Life 2020, 10(10), 234; https://doi.org/10.3390/life10100234 - 08 Oct 2020
Cited by 8 | Viewed by 2822
Abstract
Bifunctional enzymes created by the fusion of a glucuronan lyase (TrGL) and a chitinase (ThCHIT42) from Trichoderma sp. have been constructed with the aim to validate a proof of concept regarding the potential of the chimera lyase/hydrolase by analyzing the functionality and the [...] Read more.
Bifunctional enzymes created by the fusion of a glucuronan lyase (TrGL) and a chitinase (ThCHIT42) from Trichoderma sp. have been constructed with the aim to validate a proof of concept regarding the potential of the chimera lyase/hydrolase by analyzing the functionality and the efficiency of the chimeric constructions compared to parental enzymes. All the chimeric enzymes, including or nor linker (GGGGS), were shown functional with activities equivalent or higher to native enzymes. The velocity of glucuronan lyase was considerably increased for chimeras, and may involved structural modifications at the active site. The fusion has induced a slightly decrease of the thermostability of glucuronan lyase, without modifying its catalytic activity regarding pH variations ranging from 5 to 8. The biochemical properties of chitinase seemed to be more disparate between the different fusion constructions suggesting an impact of the linkers or structural interactions with the linked glucuronan lyase. The chimeric enzymes displayed a decreased stability to temperature and pH variations, compared to parental one. Overall, TrGL-ThCHIT42 offered the better compromise in terms of biochemical stability and enhanced activity, and could be a promising candidate for further experiments in the field of fungi Cell Wall-Degrading Enzymes (CWDEs). Full article
(This article belongs to the Special Issue Carbohydrate-Active Enzymes: Structure, Activity and Reaction Products 2020)
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16 pages, 6647 KiB  
Article
The Contractile Phenotype of Skeletal Muscle in TRPV1 Knockout Mice Is Gender-Specific and Exercise-Dependent
by Aude Lafoux, Sabine Lotteau, Corinne Huchet and Sylvie Ducreux
Life 2020, 10(10), 233; https://doi.org/10.3390/life10100233 - 06 Oct 2020
Cited by 5 | Viewed by 3049
Abstract
The transient receptor potential vanilloid 1 (TRPV1) belongs to the transient receptor potential superfamily of sensory receptors. TRPV1 is a non-selective cation channel permeable to Ca2+ that is capable of detecting noxious heat temperature and acidosis. In skeletal muscles, TRPV1 operates as [...] Read more.
The transient receptor potential vanilloid 1 (TRPV1) belongs to the transient receptor potential superfamily of sensory receptors. TRPV1 is a non-selective cation channel permeable to Ca2+ that is capable of detecting noxious heat temperature and acidosis. In skeletal muscles, TRPV1 operates as a reticular Ca2+-leak channel and several TRPV1 mutations have been associated with two muscle disorders: malignant hyperthermia (MH) and exertional heat stroke (EHS). Although TRPV1−/− mice have been available since the 2000s, TRPV1’s role in muscle physiology has not been thoroughly studied. Therefore, the focus of this work was to characterize the contractile phenotype of skeletal muscles of TRPV1-deficient mice at rest and after four weeks of exercise. As MS and EHS have a higher incidence in men than in women, we also investigated sex-related phenotype differences. Our results indicated that, without exercise, TRPV1−/− mice improved in vivo muscle strength with an impairment of skeletal muscle in vitro twitch features, i.e., delayed contraction and relaxation. Additionally, exercise appeared detrimental to TRPV1−/− slow-twitch muscles, especially in female animals. Full article
(This article belongs to the Section Physiology and Pathology)
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14 pages, 235 KiB  
Article
The Association of 3-Hydroxy-3-Methylglutaryl-CoA Reductase, Apolipoprotein E, and Solute Carrier Organic Anion Genetic Variants with Atorvastatin Response among Jordanian Patients with Type 2 Diabetes
by Hussam Alhawari, Yazun Jarrar, Mohammad Ahmad AlKhatib, Hussein Alhawari, Munther Momani, Ayman Zayed, Ruba Alkamhawi and Malek Zihlif
Life 2020, 10(10), 232; https://doi.org/10.3390/life10100232 - 05 Oct 2020
Cited by 8 | Viewed by 1924
Abstract
Atorvastatin is commonly used among type 2 diabetic (DM2) patients at the University of Jordan Hospital to prevent cardiovascular complication. However, we noticed that there is a wide inter-individual variation in the efficacy and toxicity of atorvastatin. This study aimed to find out [...] Read more.
Atorvastatin is commonly used among type 2 diabetic (DM2) patients at the University of Jordan Hospital to prevent cardiovascular complication. However, we noticed that there is a wide inter-individual variation in the efficacy and toxicity of atorvastatin. This study aimed to find out the effects of major genetic variants in 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), Apolipoprotein E (APOE), and Solute Carrier Organic Anion (SLCO1B1) genes on atorvastatin response among DM2 patients. A sample of 139 DM2 patients on 20 mg of atorvastatin was included in this study. The lipid and glycemic profile and the levels of hepatic enzymes alanine aminotransferase (ALT) and aspartate transaminase were recorded before and after 3 months of atorvastatin treatment. Additionally, the genetic variants HMGCR rs17244841,APOE rs7412 and rs429357, and SLCO1B1 rs2306283 and rs11045818 were genotyped using an Applied Biosystems DNA sequencing method (ABI3730×1). We found that atorvastatin reduced total cholesterol and low-density lipoprotein (LDL) more significantly (p-value < 0.05) in patients with wild genotype than variant alleles APOE rs7412C > T and SLCO1B1 rs2306283A > G. Furthermore, the ALT level was elevated significantly (p-value < 0.05) by 27% in patients with heterozygous SLCO1B1 rs11045818 G/A genotype, while it was not elevated among wild genotype carriers. Additionally, atorvastatin reduced total cholesterol more significantly (p-value < 0.05) in patients with SLCO1B1 rs2306283A and rs11045818G haplotypes and increased ALT levels by 27% (p-value < 0.05) in patients with SLCO1B1 rs2306283G and rs11045818A haplotypes. In conclusion, it was found in this study that APOE rs7412, SLCO1B1 rs2306283, and rs11045818 genotypes can be considered as potential genetic biomarkers of atorvastatin response among DM2 patients of Jordanian Arabic origin. Further clinical studies with larger sample numbers are needed to confirm these findings. Full article
(This article belongs to the Special Issue Pharmacogenomics)
17 pages, 3052 KiB  
Article
The Impact of a New Interleukin-2-Based Immunotherapy Candidate on Urothelial Cells to Support Use for Intravesical Drug Delivery
by Lisa Schmitz, Belinda Berdien, Edith Huland, Petra Dase, Karin Beutel, Margit Fisch and Oliver Engel
Life 2020, 10(10), 231; https://doi.org/10.3390/life10100231 - 05 Oct 2020
Cited by 3 | Viewed by 2450
Abstract
(1) Background: The intravesical instillation of interleukin-2 (IL-2) has been shown to be very well tolerated and promising in patients with bladder malignancies. This study aims to confirm the use of a new IL-2 containing immunotherapy candidate as safe for intravesical application. IL-2, [...] Read more.
(1) Background: The intravesical instillation of interleukin-2 (IL-2) has been shown to be very well tolerated and promising in patients with bladder malignancies. This study aims to confirm the use of a new IL-2 containing immunotherapy candidate as safe for intravesical application. IL-2, produced in mammalian cells, is glycosylated, because of its unique solubility and stability optimized for intravesical use. (2) Materials and Methods: Urothelial cells and fibroblasts were generated out of porcine bladder and cultured until they reached second passage. Afterwards, they were cultivated in renal epithelial medium (REM) and Dulbecco’s modified Eagles medium (DMEM) with the IL-2 candidate (IMS-Research) and three more types of human interleukin-2 immunotherapy products (IMS-Pure, Natural IL-2, Aldesleukin) in four different concentrations (100, 250, 500, 1000 IU/mL). Cell proliferation was analyzed by water soluble tetrazolium (WST) proliferation assay after 0, 3, and 6 days for single cell culture and co-culture. (3) Results: Proliferation assays showed that all IL-2 products induced very similar cultivation results and none of the IL-2 variants had a negative impact on the proliferation of urothelial cells and fibroblast in either concentration. (4) Conclusion: Human recombinant glycosylated IL-2 as well as human non-glycosylated IL-2 have no negative influence on the tissue cell proliferation of porcine urothelial cells and fibroblasts in vitro and represent a promising and innovative potential intravesical therapy candidate for patients in high need. Full article
(This article belongs to the Section Pharmaceutical Science)
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10 pages, 3112 KiB  
Article
Plasma Long Noncoding RNA LeXis is a Potential Diagnostic Marker for Non-Alcoholic Steatohepatitis
by Jung Gil Park, Gyeonghwa Kim, Se Young Jang, Yu Rim Lee, Eunhye Lee, Hye Won Lee, Man-Hoon Han, Jae Min Chun, Young Seok Han, Jun Sik Yoon, Min Kyu Kang, Young Oh Kweon, Won Young Tak, Soo Young Park and Keun Hur
Life 2020, 10(10), 230; https://doi.org/10.3390/life10100230 - 03 Oct 2020
Cited by 11 | Viewed by 2302
Abstract
Non-invasive diagnostic markers are needed to ease the diagnosis of non-alcoholic steatohepatitis (NASH) among patients with non-alcoholic fatty liver disease (NAFLD). The long noncoding RNA (lncRNA) LeXis is related to cholesterol metabolism and hepatic steatosis in mice, and its batch genome conversion in [...] Read more.
Non-invasive diagnostic markers are needed to ease the diagnosis of non-alcoholic steatohepatitis (NASH) among patients with non-alcoholic fatty liver disease (NAFLD). The long noncoding RNA (lncRNA) LeXis is related to cholesterol metabolism and hepatic steatosis in mice, and its batch genome conversion in humans is TCONS_00016452. Here, we aimed to evaluate the potential of lncRNA LeXis as a non-invasive diagnostic marker for NASH. We analyzed a total of 44 NAFLD patients whose diagnosis was confirmed by a pathologist through analysis of a percutaneous liver biopsy. The expression of LeXis in the plasma of NAFLD patients with and without NASH was compared using quantitative real-time polymerase chain reaction. The expression of plasma LeXis was significantly higher in patients with NASH than in those with NAFL (8.2 (5.0–14.9); 4.6 (4.0–6.6), p = 0.025). The area under the receiver operating characteristic curve was 0.743 (95% CI 0.590–0.895, p < 0.001), and a sensitivity of 54.3% and specificity of 100% could be achieved for NASH diagnosis. Low LeXis was independently associated with NASH diagnosis in patients with NAFLD (p = 0.0349, odds ratio = 22.19 (5% CI, 1.25–395.22)). Therefore, circulating lncRNA LeXis could be a potential non-invasive diagnostic biomarker for NASH. Full article
(This article belongs to the Special Issue Fatty Liver Syndrome)
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12 pages, 834 KiB  
Article
Whole Genome Sequencing and Comparative Genome Analysis of the Halotolerant Deep Sea Black Yeast Hortaea werneckii
by Orazio Romeo, Alessia Marchetta, Domenico Giosa, Letterio Giuffrè, Clara Urzì and Filomena De Leo
Life 2020, 10(10), 229; https://doi.org/10.3390/life10100229 - 02 Oct 2020
Cited by 9 | Viewed by 3354
Abstract
Hortaea werneckii, an extreme halotolerant black yeast in the order of Capnodiales, was recently isolated from different stations and depths in the Mediterranean Sea, where it was shown to be the dominant fungal species. In order to explore the genome characteristics of [...] Read more.
Hortaea werneckii, an extreme halotolerant black yeast in the order of Capnodiales, was recently isolated from different stations and depths in the Mediterranean Sea, where it was shown to be the dominant fungal species. In order to explore the genome characteristics of these Mediterranean isolates, we carried out a de-novo sequencing of the genome of one strain isolated at a depth of 3400 m (MC873) and a re-sequencing of one strain taken from a depth of 2500 m (MC848), whose genome was previously sequenced but was highly fragmented. A comparative phylogenomic analysis with other published H. werneckii genomes was also carried out to investigate the evolution of the strains from the deep sea in this environment. A high level of genome completeness was obtained for both genomes, for which genome duplication and an extensive level of heterozygosity (~4.6%) were observed, supporting the recent hypothesis that a genome duplication caused by intraspecific hybridization occurred in most H. werneckii strains. Phylogenetic analyses showed environmental and/or geographical specificity, suggesting a possible evolutionary adaptation of marine H. werneckii strains to the deep sea environment. We release high-quality genome assemblies from marine H. werneckii strains, which provides additional data for further genomics analysis, including niche adaptation, fitness and evolution studies. Full article
(This article belongs to the Special Issue Advances in Fungal -Omics)
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21 pages, 1119 KiB  
Review
The Application of Next-Generation Sequencing to Define Factors Related to Oral Cancer and Discover Novel Biomarkers
by Soyeon Kim, Joo Won Lee and Young-Seok Park
Life 2020, 10(10), 228; https://doi.org/10.3390/life10100228 - 02 Oct 2020
Cited by 21 | Viewed by 3749
Abstract
Despite the introduction of next-generation sequencing in the realm of DNA sequencing technology, it is not often used in the investigation of oral squamous cell carcinoma (OSCC). Oral cancer is one of the most frequently occurring malignancies in some parts of the world [...] Read more.
Despite the introduction of next-generation sequencing in the realm of DNA sequencing technology, it is not often used in the investigation of oral squamous cell carcinoma (OSCC). Oral cancer is one of the most frequently occurring malignancies in some parts of the world and has a high mortality rate. Patients with this malignancy are likely to have a poor prognosis and may suffer from severe facial deformity or mastication problems even after successful treatment. Therefore, a thorough understanding of this malignancy is essential to prevent and treat it. This review sought to highlight the contributions of next-generation sequencing (NGS) in unveiling the genetic alterations and differential expressions of miRNAs involved in OSCC progression. By applying an appropriate eligibility criterion, we selected relevant studies for review. Frequently identified mutations in genes such as TP53, NOTCH1, and PIK3CA are discussed. The findings of existing miRNAs (e.g., miR-21) as well as novel discoveries pertaining to OSCC are also covered. Lastly, we briefly mention the latest findings in targeted gene therapy and the potential use of miRNAs as biomarkers. Our goal is to encourage researchers to further adopt NGS in their studies and give an overview of the latest findings of OSCC treatment. Full article
(This article belongs to the Special Issue The Increasing Role of Next Generation Sequencing Methods in Mutation Analysis)
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18 pages, 3252 KiB  
Article
The Transcriptomic Analysis of NSC-34 Motor Neuron-Like Cells Reveals That Cannabigerol Influences Synaptic Pathways: A Comparative Study with Cannabidiol
by Agnese Gugliandolo, Serena Silvestro, Luigi Chiricosta, Federica Pollastro, Placido Bramanti and Emanuela Mazzon
Life 2020, 10(10), 227; https://doi.org/10.3390/life10100227 - 01 Oct 2020
Cited by 15 | Viewed by 5368
Abstract
More than 120 cannabinoids were isolated from Cannabis sativa. In particular, Cannabidiol (CBD) and Cannabigerol (CBG) represent the two most studied non-psychoactive cannabinoids. However, CBG is less studied and less data are available on its biological properties and influence on synaptic transmission. [...] Read more.
More than 120 cannabinoids were isolated from Cannabis sativa. In particular, Cannabidiol (CBD) and Cannabigerol (CBG) represent the two most studied non-psychoactive cannabinoids. However, CBG is less studied and less data are available on its biological properties and influence on synaptic transmission. On the contrary, CBD is already known to modulate brain excitatory glutamate, inhibitory γ-aminobutyric acid (GABA) and dopamine neurotransmission. In this study, using Next-Generation Sequencing (NGS) technology, we evaluated how CBG (1 or 5 µM) and CBD (1 or 5 µM) influence the transcriptome of the main neurotransmission pathways in NSC-34 motor neuron-like cells. At first, we evaluated that CBG and CBD were not cytotoxic and decreased the expression of pro-apoptotic genes. CBG and CBD are able to influence the expression of the genes involved in glutamate, GABA and dopamine signaling. Interestingly, the transcriptional changes induced by CBG were similar compared to CBD. Full article
(This article belongs to the Section Pharmaceutical Science)
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19 pages, 3212 KiB  
Article
ITRAQ Proteomic Analysis of Yellow and Black Skin in Jinbian Carp (Cyprinus carpio)
by Xiangchen Ye, Lingling Zhou, Jingyi Jia, Lingjing Wei, Yanhong Wen, Xueyu Yan, Jie Huang, Baojiang Gan, Kang Liu, Yejian Lv and Guangfu Hu
Life 2020, 10(10), 226; https://doi.org/10.3390/life10100226 - 30 Sep 2020
Cited by 3 | Viewed by 2582
Abstract
Colors are important phenotypic traits for fitness under natural conditions in vertebrates. Previous studies have reported several functional genes and genetic variations of pigmentation, but the formation mechanisms of various skin coloration remained ambiguous in fish. Jinbian carp, a common carp variant, displays [...] Read more.
Colors are important phenotypic traits for fitness under natural conditions in vertebrates. Previous studies have reported several functional genes and genetic variations of pigmentation, but the formation mechanisms of various skin coloration remained ambiguous in fish. Jinbian carp, a common carp variant, displays two colors (yellow and black) in the skin, thus, it is a good model for investigating the genetic basis of pigmentation. In the present study, using the Jinbian carp as model, isobaric tags for relative and absolute quantification (ITRAQ) proteomics analysis was performed for yellow and black skin, respectively. The results showed that 467 differentially expressed proteins (DEPs) were identified between the yellow skin and the black skin. Similar to mammals, the up-regulated DEPs in black skin included UV excision repair protein RAD23 homolog A (Rad23a), melanoregulin (mreg), 5,6-dihydroxyindole-2-carboxylic acid oxidase5 (tyrp1) and melanocyte protein PMEL (PMEL), which were mainly grouped into melanogenesis pathway. However, several up-regulated DEPs in yellow skin were mainly enriched in nucleotide metabolism, such as GTPase IMAP family member 5 (GIMAP5), AMP deaminase 1 (AMPD1), adenosylhomocysteinase b (ahcy-b), and pyruvate kinase (PKM). In summary, several candidate proteins and their enrichment pathways for color variation in Jinbian carp were identified, which may be responsible for the formation of different colorations. Full article
(This article belongs to the Special Issue Metabolic Adaptations to Environmental Pressure)
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14 pages, 3328 KiB  
Article
Ephrin Receptors (Eph): EphA1, EphA5, and EphA7 Expression in Uveal Melanoma—Associations with Clinical Parameters and Patient Survival
by Malgorzata Gajdzis, Stamatios Theocharis, Pawel Gajdzis, Nathalie Cassoux, Sophie Gardrat, Piotr Donizy, Jerzy Klijanienko and Radoslaw Kaczmarek
Life 2020, 10(10), 225; https://doi.org/10.3390/life10100225 - 30 Sep 2020
Cited by 10 | Viewed by 2075
Abstract
Uveal melanoma is the most common primary intraocular malignancy in adults. The development of distant metastases is associated with a poor prognosis. Ephrine receptors (Eph) are the largest subpopulation of tyrosine kinase receptors. They play an important role in processes related to the [...] Read more.
Uveal melanoma is the most common primary intraocular malignancy in adults. The development of distant metastases is associated with a poor prognosis. Ephrine receptors (Eph) are the largest subpopulation of tyrosine kinase receptors. They play an important role in processes related to the formation and progression of cancer. The aim of the study was to evaluate the expression of ephrin receptors EphA1, EphA5, and EphA7 in uveal melanoma and its associations with clinicopathological parameters, overall survival, and disease-free survival. The study included 94 previously untreated patients who underwent enucleation due to uveal melanoma. High expression of EphA1 was positively correlated with a smaller tumor size, less frequent extra-scleral extension, lower mitotic activity, and more frequent vitreous hemorrhage. High expression of EphA5 was associated with less frequent chromosome 3 loss, absence of distant metastases, and more frequent vitreous hemorrhage. High expression of EphA7 was associated with a more frequent primary tumor location in the posterior pole. High EphA5 expression was associated with longer overall survival time. The above findings indicate that high expression of EphA1 and EphA5 can be considered a beneficial prognostic factor in uveal melanoma. Full article
(This article belongs to the Special Issue Melanoma: Dark Tumor with Little Light for Metastasis Treatment)
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14 pages, 1122 KiB  
Article
Development of Postoperative Pain in Patients with End-Stage Knee Osteoarthritis Is Associated with Upregulation of Genes Related to Extracellular Matrix Degradation, Inflammation, and Apoptosis Measured in the Peripheral Blood before Knee Surgery
by Elena V. Tchetina, Kseniya E. Glemba, Galina A. Markova, Evgeniy A. Naryshkin, Elena A. Taskina, Maksim A. Makarov and Aleksandr M. Lila
Life 2020, 10(10), 224; https://doi.org/10.3390/life10100224 - 30 Sep 2020
Cited by 8 | Viewed by 3003
Abstract
Osteoarthritis (OA) pain implies an indication for joint replacement in patients with end-stage OA. However, chronic postoperative pain is observed in 10–40% of patients with OA. Here, we identified genes whose expression in the peripheral blood before surgery could denote the risk of [...] Read more.
Osteoarthritis (OA) pain implies an indication for joint replacement in patients with end-stage OA. However, chronic postoperative pain is observed in 10–40% of patients with OA. Here, we identified genes whose expression in the peripheral blood before surgery could denote the risk of postoperative pain development. We examined the peripheral blood of 26 healthy subjects and 50 patients with end-stage OA prior to joint replacement surgery. Pain was evaluated before surgery using the visual analog scale (VAS) index and neuropathic pain questionnaires, Douleur Neuropathique 4 Questions (DN4) and PainDETECT questionnaires. Functional activity was assessed using the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). Three and six months after surgery, pain indices according to VAS of 30% and higher were considered. Metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)1 protein levels were measured using ELISA in the peripheral blood mononuclear cells (PBMCs). Total RNA isolated from whole blood was analysed using quantitative real-time RT-PCR for caspase-3, MMP-9, TIMP1, cathepsins K and S, tumour necrosis factor (TNF)α, interleukin (IL)-1β, and cyclooxygenase (COX)-2 gene expression. Seventeen patients reported post-surgical pain. Expression of cathepsins K and S, caspase-3, TIMP1, IL-1β, and TNFα genes before surgery was significantly higher in these patients compared to pain-free patients with OA. Receiver-operating characteristic (ROC) curve analyses confirmed significant associations between these gene expressions and the likelihood of pain development after arthroplasty. High baseline expression of genes associated with extracellular matrix destruction (cathepsins S and K, TIMP1), inflammation (IL-1β, TNFα), and apoptosis (caspase-3) measured in the peripheral blood of patients with end-stage OA before knee arthroplasty might serve as an important biomarker of postoperative pain development. Full article
(This article belongs to the Special Issue Osteoarthritis Pathology and Treatment)
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16 pages, 2823 KiB  
Article
Kenaf (Hibiscus cannabinus L.) Leaves and Seed as a Potential Source of the Bioactive Compounds: Effects of Various Extraction Solvents on Biological Properties
by Md. Adnan, Ki Kwang Oh, Md Obyedul Kalam Azad, Myung Hwan Shin, Myeong-Hyeon Wang and Dong Ha Cho
Life 2020, 10(10), 223; https://doi.org/10.3390/life10100223 - 28 Sep 2020
Cited by 31 | Viewed by 5123
Abstract
Hibiscus cannabinus (Kenaf) is a potential source of bioactive constituents and natural antioxidant. The current study determined the impact of various solvents on extraction yield, recovery of polyphenol and flavonoid, antioxidant, anticancer, and antibacterial properties of Kenaf leaves and seed. The powder of [...] Read more.
Hibiscus cannabinus (Kenaf) is a potential source of bioactive constituents and natural antioxidant. The current study determined the impact of various solvents on extraction yield, recovery of polyphenol and flavonoid, antioxidant, anticancer, and antibacterial properties of Kenaf leaves and seed. The powder of leaves and seed was separately extracted with n-hexane, ethyl acetate, ethanol, and water solvent. Among them, the ethanol extract of leaves and seed showed the highest extraction yield, and their GC-MS analysis revealed a total of 55 and 14 bioactive compounds, respectively. The total polyphenols (TP) and flavonoids (TF) content were quantified by a spectrophotometric technique where water extracts displayed a noteworthy amount of TP and TF content compared to other extracts. A similar demonstration was noticed in antioxidant activity, evaluated by DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydrogen peroxide scavenging capacity. In addition, cytotoxicity and anti-lung cancer activity were identified against mouse embryonic fibroblast (NIH3T3) and human lung cancer (A549) cells. All extracts of leaves and seed were observed as non-toxic to the NIH3T3 cells, but slight toxicity was expressed by n-hexane extracts at the optimum dose (1000 µg/mL) of treatment. In parallel, n-hexane and ethanol extracts (leaves and seed) exposed promising anti-lung cancer activity at the same concentration. Furthermore, antibacterial activity was assessed using disc diffusion assay, and seed extracts exhibited a significant inhibition zone against Gram-positive and Gram-negative microorganisms. Overall, Kenaf seed extracted with polar solvents was found very potent in terms of important bioactive compounds and pharmacological aspects, which can be an excellent biological matrix of natural antioxidants. Full article
(This article belongs to the Section Pharmaceutical Science)
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1 pages, 170 KiB  
Erratum
Erratum: Pérez-Belmonte, S., et al. Subtypes of Depression: Latent Class Analysis in Spanish Old People with Depressive Symptoms. Life 2020, 10, 70
by Sergio Pérez-Belmonte, Laura Galiana, Patricia Sancho, Amparo Oliver and José M. Tomás
Life 2020, 10(10), 222; https://doi.org/10.3390/life10100222 - 27 Sep 2020
Cited by 1 | Viewed by 1403
Abstract
The authors wish to make the following erratum to this paper [...] Full article
(This article belongs to the Special Issue Mental Health Issues and Quality of Life in Older Individuals)
23 pages, 1021 KiB  
Review
Mobile Elements in Ray-Finned Fish Genomes
by Federica Carducci, Marco Barucca, Adriana Canapa, Elisa Carotti and Maria Assunta Biscotti
Life 2020, 10(10), 221; https://doi.org/10.3390/life10100221 - 25 Sep 2020
Cited by 16 | Viewed by 3961
Abstract
Ray-finned fishes (Actinopterygii) are a very diverse group of vertebrates, encompassing species adapted to live in freshwater and marine environments, from the deep sea to high mountain streams. Genome sequencing offers a genetic resource for investigating the molecular bases of this phenotypic diversity [...] Read more.
Ray-finned fishes (Actinopterygii) are a very diverse group of vertebrates, encompassing species adapted to live in freshwater and marine environments, from the deep sea to high mountain streams. Genome sequencing offers a genetic resource for investigating the molecular bases of this phenotypic diversity and these adaptations to various habitats. The wide range of genome sizes observed in fishes is due to the role of transposable elements (TEs), which are powerful drivers of species diversity. Analyses performed to date provide evidence that class II DNA transposons are the most abundant component in most fish genomes and that compared to other vertebrate genomes, many TE superfamilies are present in actinopterygians. Moreover, specific TEs have been reported in ray-finned fishes as a possible result of an intricate relationship between TE evolution and the environment. The data summarized here underline the biological interest in Actinopterygii as a model group to investigate the mechanisms responsible for the high biodiversity observed in this taxon. Full article
(This article belongs to the Special Issue The Mobilome in Vertebrate Genomes)
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13 pages, 221 KiB  
Review
Nutrient and Dietary Patterns in Relation to the Pathogenesis of Postmenopausal Osteoporosis—A Literature Review
by Bolaji Lilian Ilesanmi-Oyelere and Marlena C. Kruger
Life 2020, 10(10), 220; https://doi.org/10.3390/life10100220 - 25 Sep 2020
Cited by 21 | Viewed by 3872
Abstract
Postmenopausal women tend to be susceptible to primary osteoporosis due to its association with oestrogen deficiency. There is emerging evidence that an unhealthy dietary pattern drives an increase in the risk of postmenopausal osteoporosis (PO), whereas a healthy dietary pattern may decrease its [...] Read more.
Postmenopausal women tend to be susceptible to primary osteoporosis due to its association with oestrogen deficiency. There is emerging evidence that an unhealthy dietary pattern drives an increase in the risk of postmenopausal osteoporosis (PO), whereas a healthy dietary pattern may decrease its occurrence. In this narrative literature review, we sought to review the role of nutrient and dietary patterns in the pathogenesis of PO. Therefore, we searched and reported all research articles from 2001 to May 2020 in Web of Science, Cinahl and Scopus that have researched a relationship between nutrient and/or dietary patterns and postmenopausal osteoporosis. Nutrients such as calcium, phosphorus, magnesium and vitamin D have been proven to be beneficial for bone health. Meanwhile, for the dietary patterns, foods such as dairy products especially milk, fibre and protein-rich foods, e.g., meat were directly linked to a positive association with bone mineral density (BMD). Likewise, fruits, vegetables and probiotic and prebiotic foods were reported for its positive relationship with BMD. Therefore, aside from physical activity, nutrition and diet in adequate proportions are suggested to be an important tool for ameliorating osteoporosis and bone health issues in older age. Full article
(This article belongs to the Section Physiology and Pathology)
25 pages, 1089 KiB  
Review
The Tumor and Host Immune Signature, and the Gut Microbiota as Predictive Biomarkers for Immune Checkpoint Inhibitor Response in Melanoma Patients
by Katarzyna Tomela, Bernadeta Pietrzak, Marcin Schmidt and Andrzej Mackiewicz
Life 2020, 10(10), 219; https://doi.org/10.3390/life10100219 - 25 Sep 2020
Cited by 11 | Viewed by 3374
Abstract
There are various melanoma treatment strategies that are based on immunological responses, among which immune checkpoint inhibitors (ICI) are relatively novel form. Nowadays, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) antibodies represent a standard treatment for metastatic melanoma. Although there are [...] Read more.
There are various melanoma treatment strategies that are based on immunological responses, among which immune checkpoint inhibitors (ICI) are relatively novel form. Nowadays, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) antibodies represent a standard treatment for metastatic melanoma. Although there are remarkable curative effects in responders to ICI therapy, up to 70% of melanoma patients show resistance to this treatment. This low response rate is caused by innate as well as acquired resistance, and some aspects of treatment resistance are still unknown. Growing evidence shows that gut microbiota and bacterial metabolites, such as short-chain fatty acids (SCFAs), affect the efficacy of immunotherapy. Various bacterial species have been indicated as potential biomarkers of anti-PD-1 or anti-CTLA-4 therapy efficacy in melanoma, next to biomarkers related to molecular and genetic tumor characteristics or the host immunological response, which are detected in patients’ blood. Here, we review the current status of biomarkers of response to ICI melanoma therapies, their pre-treatment predictive values, and their utility as on-treatment monitoring tools in order to select a relevant personalized therapy on the basis of probability of the best clinical outcome. Full article
(This article belongs to the Special Issue Melanoma: Dark Tumor with Little Light for Metastasis Treatment)
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