Melatonin-Index as a biomarker for predicting the distribution of presymptomatic and asymptomatic SARS-CoV-2 carriers

2021 ◽  
Vol 4 (1) ◽  
pp. 189-205
Author(s):  
Pedro A Fernandes ◽  
Gabriela S Kinker ◽  
Bruno V Navarro ◽  
Vinicius C Jardim ◽  
Edson D Ribeiro-Paz ◽  
...  

The pandemic dissemination of the SARS-CoV-2 led, on the one hand, to a worldwide effort to develop mechanistic-based therapeutics and vaccines, and on the other hand, the searching for determining the spreaders and the mechanisms of transmission. Melatonin, a multitask molecule, orchestrates defense responses by allowing the proper mounting, duration, and magnitude of innate immune responses. Melatonin is synthesized on demand by immune-competent cells and constitutively by resident macrophages such as alveolar macrophages. Here we investigated whether the expression of genes relevant to virus invasion and infection varies according to a genic index (MEL-Index) that estimates the capacity of the lung to synthesize melatonin. A COVID-19-Signature composed of 455 genes of 288 human lungs (GTEX, UCSD) was correlated with MEL-Index by Pearson correlation test, gene-set enrichment analysis, and networking tool that integrates the connectivity between the most expressed genes, allowing us to compare the same set of genes under different states. The three independent procedures point to a negative relationship between MEL-Index and SARS-CoV-2 infection. The entry in epithelial AT2 cells should be hampered by a positive correlation TMRPSS2  and a negative correlation with the coding gene for furin, suggesting dysfunctional processing in virus spike. Moreover, MEL-Index also negatively correlates with the genes that codify the proteins of multi-molecular receptor complex CD147, the gateway in macrophages, and other immune cells. In summary, the perspective that lung and respiratory tract melatonin could be a natural protective factor opens new epidemiological and pharmacological perspectives, as high MEL-Index scores could be predictive of asymptomatic carriers, and nasal administrated melatonin could prevent evolution of presymptomatic carriers.

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2544
Author(s):  
Ryo Inotsuka ◽  
Miyako Udono ◽  
Atsushi Yamatsu ◽  
Mujo Kim ◽  
Yoshinori Katakura

γ-Aminobutyric acid (GABA) is a potent bioactive amino acid, and several studies have shown that oral administration of GABA induces relaxation, improves sleep, and reduces psychological stress and fatigue. In a recent study, we reported that exosomes derived from GABA-treated intestinal cells serve as signal transducers that mediate brain–gut interactions. Therefore, the purpose of this study was to verify the functionality of GABA-derived exosomes and to examine the possibility of improving memory function following GABA administration. The results showed that exosomes derived from GABA-treated intestinal cells (Caco-2) activated neuronal cells (SH-SY5Y) by regulating genes related to neuronal cell functions. Furthermore, we found that exosomes derived from the serum of GABA-treated mice also activated SH-SY5Y cells, indicating that exosomes, which are capable of activating neuronal cells, circulate in the blood of mice orally administered GABA. Finally, we performed a microarray analysis of mRNA isolated from the hippocampus of mice that were orally administered GABA. The results revealed changes in the expression of genes related to brain function. Gene Set Enrichment Analysis (GSEA) showed that oral administration of GABA affected the expression of genes related to memory function in the hippocampus.


2021 ◽  
Vol 12 ◽  
Author(s):  
Chunxia Zhao ◽  
Yulu Wang ◽  
Famei Tu ◽  
Shuai Zhao ◽  
Xiaoying Ye ◽  
...  

BackgroundSome studies have proven that autophagy and lncRNA play important roles in AML. Several autophagy related lncRNA signatures have been shown to affect the survival of patients in some other cancers. However, the role of autophagy related lncRNA in AML has not been explored yet. Hence, this study aims to find an autophagy related lncRNA signature that can affect survival for AML patients.MethodA Pearson correlation analysis, a Kaplan–Meier survival curve, a univariate cox regression, and a multivariate cox regression were performed to establish an autophagy related lncRNA signature. A univariate cox regression, a multivariate cox regression, a Kaplan–Meier survival curve, and a ROC curve were applied to confirm if the signature is an independent prognosis for AML patients. The relationship between the signature and the clinical features was explored by using a T test. Gene Set Enrichment Analysis (GSEA) was used to investigate the potential tumor related pathways.ResultsA four-autophagy related lncRNA (MIR133A1HG, AL359715.1, MIRLET7BHG, and AL356752.1) signature was established. The high risk score based on signature was related to the short survival time of AML patients. The signature was an independent factor for the prognosis for AML patients (HR = 1.684, 95% CI = 1.324–2.142, P < 0.001). The signature was correlated with age, leukocyte numbers, and FAB (M3 or non-M3). The P53, IL6/JAK/STAT3, TNF-α, INF-γ, and IL2/STAT5 pathways might contribute to the differences between the risk groups based on signature in AML.ConclusionThe four autophagy related lncRNAs and their signature might be novel biomarkers for predicting the survival of AML patients. Some biological pathways might be the potential mechanisms of the signature for the survival of AML patients.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 570-570
Author(s):  
Sebastian Schaaf ◽  
Matthias Froelich ◽  
Thomas Kirchner ◽  
Volker Heinemann ◽  
Andreas Jung ◽  
...  

570 Background: Colorectal cancer (CRC) treatment with the EGFR-inhibitory antibody Cetuximab (CTX) is known to cause skin rashes (SR) of varying degree in most patients. Severity of SR is positively associated with tumor response. The underlying molecular mechanism linking both effects is still unknown. Detangling its genetic background would allow a simultaneous understanding of SR and response. Stratification of patients based on the related polymorphisms (PMs) is of clinical relevance. Methods: A systematic literature review was performed to develop a molecular map which incorporates specific pathways related to cancer, CTX specific mechanisms of action, skin rash, and autoimmunity. Exome data was generated from blood samples of 23 KRAS wild type patients taken prior to CTX treatment. Under CTX, eleven of the 23 patients showed SR of grades 3-4, twelve reacted with a grade 1 SR. Differential somatic PMs were analyzed between both groups. A gene set enrichment analysis for the imbalanced PMs was performed against gene sets of our molecular map. Imbalance was stated if at least seven patients more in the one group compared to the other carried this specific PM. Results: A total of 591 genes containing imbalanced PMs were found. Bioinformatic validation focused on the following findings of potential clinical interest: (1) PMs in genes specifically related to cell adhesion (CDH1, LAMC1, FBN2, NCAM1) or its regulation (WNT9B), (2) to autoimmunity (CXCL16, ADAM12, OS9, DOCK2), (3) in the central regulator TP53, (4) in genes playing a role in immunity and cell adhesion (DOCK2 and THBS2). PMs in the mentioned genes enabled to discriminate patients with and without severe skin rash. Validation of these findings is needed based on new independent CTX treated patients. Conclusions: Our findings suggest that genomic predisposition may exist which interact with CTX treatment by inducing alteration of cell adhesion. Altering adhesion between tumor cells makes them more accessible to the EGFR-inhibitory effect of CTX. Altering cell adhesion between epithelial cells introduces the acne like phenotypes of skin rash, presumably via the mechanism of epithelial activation. This will be the starting point for further research.


2009 ◽  
Vol 38 (3) ◽  
pp. 342-350 ◽  
Author(s):  
Stephen Welle ◽  
Andrew Cardillo ◽  
Michelle Zanche ◽  
Rabi Tawil

There is much interest in developing anti-myostatin agents to reverse or prevent muscle atrophy in adults, so it is important to characterize the effects of reducing myostatin activity after normal muscle development. For assessment of the effect of loss of myostatin signaling on gene expression in muscle, RNA from mice with postdevelopmental myostatin knockout was analyzed with oligonucleotide microarrays. Myostatin was undetectable in muscle within 2 wk after Cre recombinase activation in 4-month-old male mice with floxed myostatin genes. Three months after myostatin depletion, muscle mass had increased 26% (vs. 2% after induction of Cre activity in mice with normal myostatin genes), at which time the expression of several hundred genes differed in knockout and control mice at nominal P < 0.01. In contrast to previously reported effects of constitutive myostatin knockout, postdevelopmental knockout did not downregulate expression of genes encoding slow isoforms of contractile proteins or genes encoding proteins involved in energy metabolism. Several collagen genes were expressed at 20–50% lower levels in the myostatin-deficient muscles, which had ∼25% less collagen than normal muscles as reflected by hydroxyproline content. Most of the other genes affected by myostatin depletion have not been previously linked to myostatin signaling. Gene set enrichment analysis suggested that Smads are not the only transcription factors with reduced activity after myostatin depletion. These data reinforce other evidence that myostatin regulates collagen production in muscle and demonstrate that many of the previously reported effects of constitutive myostatin deficiency do not occur when myostatin is knocked out in mature muscles.


2021 ◽  
Vol 13 (1) ◽  
pp. 133-143
Author(s):  
Ilimdar Yalcin ◽  
Gamze Yildirim Araz ◽  
Laurentiu-Gabriel Talaghir

This study aims to investigate the relationship between amateur football players’ mental readiness and difficulty in dealing with the level of emotion regulation. The study group consisted of 219 volunteer male athletes who actively played amateur league football in Bingol, Turkey during the 2018-2019 season. Along with a consideration of various demographic variables, the “Mental Readiness Scale” and the “Difficulty in Emotion Regulation Scale” have been used in this study. SPSS packaged software has been utilized for data analysis purposes. Descriptive statistics, Pearson Correlation and the One-Way ANOVA test have been utilized in the data analysis. According to the findings, a negative relationship has been determined between mental readiness and difficulty in emotion regulation on the part of the amateur football players. Furthermore, a statistically significant difference has been found between the variable of the football playing year and the total degree of mental readiness, mental preparation, cool-headedness and goals sub-dimensions (p< .05). Moreover, another statistically significant difference has been determined between the variable working period with the current coach and the total degree of mental readiness, mental preparation and cool-headedness sub-dimensions. As a consequence, the results suggest that as the mental readiness levels of the amateur players taking part in the study increase, the difficulty they experience in emotion regulation decreases. Additionally, it has been found out that as the football playing year and working period with the current coach increases, the athletes’ mental readiness levels go up, and the level of difficulty with regard to emotion regulation decreases.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jingyi Chen ◽  
Yuxuan Song ◽  
Mei Li ◽  
Yu Zhang ◽  
Tingru Lin ◽  
...  

Abstract Background Competing endogenous RNA (ceRNA) represents a class of RNAs (e.g., long noncoding RNAs [lncRNAs]) with microRNA (miRNA) binding sites, which can competitively bind miRNA and inhibit its regulation of target genes. Increasing evidence has underscored the involvement of dysregulated ceRNA networks in the occurrence and progression of colorectal cancer (CRC). The purpose of this study was to construct a ceRNA network related to the prognosis of CRC and further explore the potential mechanisms that affect this prognosis. Methods RNA-Seq and miRNA-Seq data from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed lncRNAs (DElncRNAs), microRNAs (DEmiRNAs), and mRNAs (DEmRNAs), and a prognosis-related ceRNA network was constructed based on DElncRNA survival analysis. Subsequently, pathway enrichment, Pearson correlation, and Gene Set Enrichment Analysis (GSEA) were performed to determine the function of the genes in the ceRNA network. Gene Expression Profiling Interactive Analysis (GEPIA) and immunohistochemistry (IHC) were also used to validate differential gene expression. Finally, the correlation between lncRNA and immune cell infiltration in the tumor microenvironment was evaluated based on the CIBERSORT algorithm. Results A prognostic ceRNA network was constructed with eleven key survival-related DElncRNAs (MIR4435-2HG, NKILA, AFAP1-AS1, ELFN1-AS1, AC005520.2, AC245884.8, AL354836.1, AL355987.4, AL591845.1, LINC02038, and AC104823.1), 54 DEmiRNAs, and 308 DEmRNAs. The MIR4435-2HG- and ELFN1-AS1-associated ceRNA subnetworks affected and regulated the expression of the COL5A2, LOX, OSBPL3, PLAU, VCAN, SRM, and E2F1 target genes and were found to be related to prognosis and tumor-infiltrating immune cell types. Conclusions MIR4435-2HG and ELFN1-AS1 are associated with prognosis and tumor-infiltrating immune cell types and could represent potential prognostic biomarkers or therapeutic targets in colorectal carcinoma.


Author(s):  
Sandra I. Jiménez-Gayosso DDS ◽  
Edith Lara-Carrillo DDS, MSc, PhD ◽  
Rogelio J. Scougall-Vilchis DDS, MSc, PhD ◽  
Raúl A. Morales-Luckie BS Chem, PhD ◽  
Carlo E. Medina Solís DDS, MSc ◽  
...  

The aim of this study was to explore the remineralizing effect of toothpastes based on Xilitol, Camellia Sinensis and Juniperus Communis. An in vitro experimental study was carried out in an 18 human premolars sample, which were treated with one of the 3 evaluated toothpastes and a control fluoride one. The atomic percentages of Ca and P were evaluated by Energy Dispersive X-ray Spectroscopy (EDS). In addition, the enamel surface of treated teeth was visualized by Scanning Electron Microscopy (SEM). The evaluations were carried out in three stages: pre-treatment, after an artificial demineralization process and after the treatment with the toothpastes. In the statistical analysis, the one-way ANOVA and Pearson correlation tests were used. Xilitol and Juniperus Communis showed the greatest gain of P ions compared to the control group (p<0.01). As for Ca, the group treated with xylitol-based toothpaste showed more ion gain compared with the control group (p<0.01). In the Pearson correlation test between Ca and P, statistically significant correlations were observed in all groups (p<0.01), ranging between r=0.7413 (Xylitol Group) and r=0.9510 (Control Group). We concluded that Xylitol paste showed the highest remineralizing property, both in the EDS analysis and in the SEM images.


2021 ◽  
Vol 10 ◽  
Author(s):  
Yangyang Wang ◽  
Wenjianlong Zhou ◽  
Shunchang Ma ◽  
Xiudong Guan ◽  
Dainan Zhang ◽  
...  

Glycolysis refers to one of the critical phenotypes of tumor cells, regulating tumor cell phenotypes and generating sufficient energy for glioma cells. A range of noticeable genes [such as isocitrate dehydrogenase (IDH), phosphatase, and tensin homolog (PTEN), or Ras] overall impact cell proliferation, invasion, cell cycle, and metastasis through glycolysis. Moreover, long non-coding RNAs (LncRNAs) are increasingly critical to disease progression. Accordingly, this study aimed to identify whether glycolysis-related LncRNAs have potential prognostic value for glioma patients. First, co-expression network between glycolysis-related protein-coding RNAs and LncRNAs was established according to Pearson correlation (Filter: |r| &gt; 0.5 &amp; P &lt; 0.001). Furthermore, based on univariate Cox regression, the Least Absolute Shrinkage and Selection Operator (LASSO) analysis and multivariate Cox regression, a predictive model were built; vital glycolysis-related LncRNAs were identified; the risk score of every single patient was calculated. Moreover, receiver operating characteristic (ROC) curve analysis, gene set enrichment analysis (GSEA), GO and KEGG enrichment analysis were performed to assess the effect of risk score among glioma patients. 685 cases (including RNA sequences and clinical information) from two different cohorts of the Chinese Glioma Genome Atlas (CGGA) database were acquired. Based on the mentioned methods, the risk score calculation formula was yielded as follows: Risk score = (0.19 × EXPFOXD2-AS1) + (−0.27 × EXPAC062021.1) + (−0.16 × EXPAF131216.5) + (−0.05 × EXPLINC00844) + (0.11 × EXPCRNDE) + (0.35 × EXPLINC00665). The risk score was independently related to prognosis, and every single mentioned LncRNAs was significantly related to the overall survival of patients. Moreover, functional enrichment analysis indicated that the biologic process of the high-risk score was mainly involved in the cell cycle and DNA replication signaling pathway. This study confirmed that glycolysis-related LncRNAs significantly impact poor prognosis and short overall survival and may act as therapeutic targets in the future.


2021 ◽  
Vol 12 (22) ◽  
pp. 23-41
Author(s):  
Omer Akgun Tekin ◽  
Alparslan Abdullah Turhan

The potential relationship between social media addiction and personality traits is an essential topic in tourism studies, though it is rarely examined. Thus, this study aims to examine whether undergraduate tourism students are addicted to social media and, if so, the possible relationship between this addiction and their personality traits. The research used the descriptive method, one of the quantitative research methods. The questionnaire technique and the convenience sampling method were preferred to amass the data. Data were collected from 454 undergraduate tourism students and analyzed with the Pearson correlation test by using SPSS 25. This research has revealed that the students' dominant personality trait is agreeableness with a low-level social media addiction. The research has also found a positive relationship between neuroticism personality traits and social media addiction and a negative relationship between personality traits of extraversion, agreeableness, and conscientiousness, and social media addiction. The research has revealed that tourism students are dependent on social media. Social media addiction is a type of addiction that harms individuals' personal development and business life. Accordingly, theoretical and practical studies should be carried out to combat this addiction. To this end, it is crucial to develop more sophisticated combating methods according to an individual's personality traits and carry out awareness and training studies in the practical field. The literature has scarcely examined the relationship between undergraduate tourism students' personality traits and social media addiction. Therefore, this study is believed to contribute to filling an important gap in the literature.


2021 ◽  
Vol 12 (1) ◽  
pp. 16-20
Author(s):  
Tonmoy Chowdhury ◽  

Before 1990, foreign investors could not extensively invest in Brazil because of its stringent and conservative trade policy. However, in 1990 Brazil took a remarkable shift in its trade policy from its previous trends by taking a liberal stance in terms of FDI inflow. The liberal trade policy that Brazil took in 1990 remove all the trade barriers that previously hindered the free flow of FDI in Brazil, the sign of which had been reflected in the steady and gradual incremental FDI inflow in the country after that. This New opening of trade atmosphere had brought with it two very different repercussions. In one hand, it accelerated the economic growth by bringing in investment in the needed sectors; on the other hand this acceleration spurred industrial activities that are accompanied by air and water pollution and deforestation as a byproduct. Since then, environmental health and ecosystem of Brazil have been facing tremendous threat owing to these pollution problems which may indirectly distress the EPI score of Brazil. Keeping these issues in mind, the present study investigates the relationship between FDI inflow and EPI score in Brazil. With the help of descriptive statistical tools as well as Pearson correlation test, this study finds the negative relationship between FDI inflow and EPI score in Brazil.


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