scholarly journals Candidate genes of SARS-CoV-2 gender susceptibility

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cristina Russo ◽  
Giovanna Morello ◽  
Roberta Malaguarnera ◽  
Salvatore Piro ◽  
Debora Lo Furno ◽  
...  

AbstractThe severe acute respiratory syndrome coronavirus (SARS-CoV-2) initiated a global viral pandemic since late 2019. Understanding that Coronavirus disease (COVID-19) disproportionately affects men than women results in great challenges. Although there is a growing body of published study on this topic, effective explanations underlying these sex differences and their effects on the infection outcome still remain uncertain. We applied a holistic bioinformatics method to investigate molecular variations of known SARS-CoV-2 interacting human proteins mainly expressed in gonadal tissues (testis and ovary), allowing for the identification of potential genetic targets for this infection. Functional enrichment and interaction network analyses were also performed to better investigate the biological differences between testicular and ovarian responses in the SARS-CoV-2 infection, paying particular attention to genes linked to immune-related pathways, reactions of host cells after intracellular infection, steroid hormone biosynthesis, receptor signaling, and the complement cascade, in order to evaluate their potential association with sexual difference in the likelihood of infection and severity of symptoms. The analysis revealed that within the testis network TMPRSS2, ADAM10, SERPING1, and CCR5 were present, while within the ovary network we found BST2, GATA1, ENPEP, TLR4, TLR7, IRF1, and IRF2. Our findings could provide potential targets for forthcoming experimental investigation related to SARS-CoV-2 treatment.

2021 ◽  
Vol 28 (1) ◽  
pp. 20-33
Author(s):  
Lydia-Eirini Giannakou ◽  
Athanasios-Stefanos Giannopoulos ◽  
Chrissi Hatzoglou ◽  
Konstantinos I. Gourgoulianis ◽  
Erasmia Rouka ◽  
...  

Haemophilus influenzae (Hi), Moraxella catarrhalis (MorCa) and Pseudomonas aeruginosa (Psa) are three of the most common gram-negative bacteria responsible for human respiratory diseases. In this study, we aimed to identify, using the functional enrichment analysis (FEA), the human gene interaction network with the aforementioned bacteria in order to elucidate the full spectrum of induced pathogenicity. The Human Pathogen Interaction Database (HPIDB 3.0) was used to identify the human proteins that interact with the three pathogens. FEA was performed via the ToppFun tool of the ToppGene Suite and the GeneCodis database so as to identify enriched gene ontologies (GO) of biological processes (BP), cellular components (CC) and diseases. In total, 11 human proteins were found to interact with the bacterial pathogens. FEA of BP GOs revealed associations with mitochondrial membrane permeability relative to apoptotic pathways. FEA of CC GOs revealed associations with focal adhesion, cell junctions and exosomes. The most significantly enriched annotations in diseases and pathways were lung adenocarcinoma and cell cycle, respectively. Our results suggest that the Hi, MorCa and Psa pathogens could be related to the pathogenesis and/or progression of lung adenocarcinoma via the targeting of the epithelial cellular junctions and the subsequent deregulation of the cell adhesion and apoptotic pathways. These hypotheses should be experimentally validated.


2019 ◽  
Author(s):  
Xian Zou ◽  
Tingting Lu ◽  
Zhifeng Zhao ◽  
Guangbin Liu ◽  
Zhiquan Lian ◽  
...  

Abstract Background Fertility is an important economic trait in production of meat goat, and follicular development plays an important role in fertility. Despite many mRNAs and microRNAs (miRNAs) have been found in playing critical roles in ovarian biological processes, the interactions between mRNAs and miRNAs in follicular development is not yet completely understood. In addition, less attention has been given to the single follicle (dominant or atretic follicle) in goat. The study was aimed to identify mRNAs, miRNAs and signaling pathways as well as their interaction networks in the ovarian follicles (large follicles and small follicles) of multiple and uniparous goats (Chuanzhong Black Goats) at estrus phase by using a deep RNA-sequencing (RNA-seq) method.Results The result showed that there were more large follicles in multiple than in uniparous goats ( P <0.05), while no difference was observed in small follicles between them ( P >0.05). For the small follicles of multiple and uniparous goats at estrus phase, 289 differentially expressed mRNAs (DEmRNAs) and 16 DEmiRNAs were identified; and for the large follicles, 195 DEmRNAs and 7 DEmiRNAs were identified. Ovarian steroidogenesis and steroid hormone biosynthesis were significantly enriched in small follicles, while ABC transporters and steroid hormone biosynthesis in large follicles. The results of qRT-PCR were generally consistent with the RNA-seq data. The mRNA-miRNA interaction network showed that CD36 (miR-122, miR-200a, miR-141), TNFAIP6 (miR-141, miR-200a, miR-182), CYP11A1 (miR-122), SERPINA5 (miR-1, miR-206, miR-133a-3p, miR-133b) and PTGFR (miR-182, miR-122) might be related to fertility, but need further verification.Conclusion This study provides the first identification of the DEmRNAs and DEmiRNAs as well as their interactions in the follicles of multiple and uniparous goats at estrus phase by using RNA-seq technology. These analyses provide new clues to uncover molecular mechanisms and signaling networks of goat reproduction which could be potentially used to increase ovulation rate and kidding rate in goat.


2021 ◽  
Author(s):  
Qi-Shun Geng ◽  
Zhi-Bo Shen ◽  
Li-Feng Li ◽  
Jie Zhao

Abstract Background. Thyroid cancer (THCA) is a malignancy affecting the endocrine system, which currently has no effective treatment due to a limited number of suitable drugs and prognostic markers. Methods. Three Gene Expression Omnibus (GEO) datasets were selected to identify differentially expressed genes (DEGs) between THCA and normal thyroid samples using GEO2R tools of National Center for Biotechnology Information. We identified hub gene FN1 using functional enrichment and protein–protein interaction network analyses. Subsequently, we evaluated the importance of gene expression on clinical prognosis using The Cancer Genome Atlas (TCGA) database and GEO datasets. MEXPRESS was used to investigate the correlation between gene expression and DNA methylation; the correlations between FN1 and cancer immune infiltrates were investigated using CIBERSORT. In addition, we assessed the effect of silencing FN1 expression, using an in vitro cellular model of THCA. Immunohistochemical(IHC) was used to elevate the correlation between CD276 and FN1. Results. FN1 expression was highly correlated with progression-free survival and moderately to strongly correlated with the infiltration levels of M2 macrophages and resting memory CD4 + T cells, as well as with CD276 expression. We suggest promoter hypermethylation as the mechanism underlying the observed changes in FN1 expression, as 20 CpG sites in 507 THCA cases in TCGA database showed a negative correlation with FN1 expression. In addition, silencing FN1 expression suppressed clonogenicity, motility, invasiveness, and expression of CD276 in vitro. The correlation between FN1 and CD276 was further confirmed by immunohistochemical. Conclusion. Our findings show that FN1 expression levels correlate with prognosis and immune infiltration levels in THCA, suggesting that FN1 expression be used as immunity-related biomarker and therapeutic target in THCA.


2020 ◽  
Vol 11 ◽  
Author(s):  
Yang Xu ◽  
Xiaoxia Li ◽  
Wenxing Liang ◽  
Mengjie Liu

Posttranslational modifications (PTMs) of the whole proteome have become a hot topic in the research field of epigenetics, and an increasing number of PTM types have been identified and shown to play significant roles in different cellular processes. Protein lysine 2-hydroxyisobutyrylation (Khib) is a newly detected PTM, and the 2-hydroxyisobutyrylome has been identified in several species. Botrytis cinerea is recognized as one of the most destructive pathogens due to its broad host distribution and very large economic losses; thus the many aspects of its pathogenesis have been continuously studied. However, distribution and function of Khib in this phytopathogenic fungus are not clear. In this study, a proteome-wide analysis of Khib in B. cinerea was performed, and 5,398 Khib sites on 1,181 proteins were identified. Bioinformatics analysis showed that the 2-hydroxyisobutyrylome in B. cinerea contains both conserved proteins and novel proteins when compared with Khib proteins in other species. Functional classification, functional enrichment and protein interaction network analyses showed that Khib proteins are widely distributed in cellular compartments and involved in diverse cellular processes. Significantly, 37 proteins involved in different aspects of regulating the pathogenicity of B. cinerea were detected as Khib proteins. Our results provide a comprehensive view of the 2-hydroxyisobutyrylome and lay a foundation for further studying the regulatory mechanism of Khib in both B. cinerea and other plant pathogens.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhongyuan Lin ◽  
Yimin Wang ◽  
Shiqing Lin ◽  
Decheng Liu ◽  
Guohui Mo ◽  
...  

Abstract Background Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disease characterized by chronic abdominal discomfort and pain. The mechanisms of abdominal pain, as a relevant symptom, in IBS are still unclear. We aimed to explore the key genes and neurobiological changes specially involved in abdominal pain in IBS. Methods Gene expression data (GSE36701) was downloaded from Gene Expression Omnibus database. Fifty-three rectal mucosa samples from 27 irritable bowel syndrome with diarrhea (IBS-D) patients and 40 samples from 21 healthy volunteers as controls were included. Differentially expressed genes (DEGs) between two groups were identified using the GEO2R online tool. Functional enrichment analysis of DEGs was performed on the DAVID database. Then a protein–protein interaction network was constructed and visualized using STRING database and Cytoscape. Results The microarray analysis demonstrated a subset of genes (CCKBR, CCL13, ACPP, BDKRB2, GRPR, SLC1A2, NPFF, P2RX4, TRPA1, CCKBR, TLX2, MRGPRX3, PAX2, CXCR1) specially involved in pain transmission. Among these genes, we identified GRPR, NPFF and TRPA1 genes as potential biomarkers for irritating abdominal pain of IBS patients. Conclusions Overexpression of certain pain-related genes (GRPR, NPFF and TRPA1) may contribute to chronic visceral hypersensitivity, therefore be partly responsible for recurrent abdominal pain or discomfort in IBS patients. Several synapses modification and biological process of psychological distress may be risk factors of IBS.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mingkang Yang ◽  
Liping Wang ◽  
Chumin Chen ◽  
Xu Guo ◽  
Chuanglie Lin ◽  
...  

AbstractAutophagy is a highly conserved process of degradation of cytoplasmic constituents in eukaryotes. It is involved in the growth and development of plants, as well as in biotic and abiotic stress response. Although autophagy-related (ATG) genes have been identified and characterized in many plant species, little is known about this process in Medicago truncatula. In this study, 39 ATGs were identified, and their gene structures and conserved domains were systematically characterized in M. truncatula. Many cis-elements, related to hormone and stress responsiveness, were identified in the promoters of MtATGs. Phylogenetic and interaction network analyses suggested that the function of MtATGs is evolutionarily conserved in Arabidopsis and M. truncatula. The expression of MtATGs, at varied levels, was detected in all examined tissues. In addition, most of the MtATGs were highly induced during seed development and drought stress, which indicates that autophagy plays an important role in seed development and responses to drought stress in M. truncatula. In conclusion, this study gives a comprehensive overview of MtATGs and provides important clues for further functional analysis of autophagy in M. truncatula.


2020 ◽  
Author(s):  
SANGEETA KUMARI

Abstract Objective This study’s primary goal is unraveling the mechanism of action of bioactives of Curcuma longa L. at the molecular level using protein-protein interaction network.Results We used target proteins to create protein-protein interaction network (PPIN) and identified significant node and edge attributes of PPIN. We identified the cluster of proteins in the PPIN, which were used to identify enriched pathways. . We identified closeness centrality and jaccard score as most important node and edge attribute of the PPIN respectively. The enriched pathways of various clusters were overlapped suggesting synergistic mechanism of action. The three pathways found to be common among three clusters were Gonadotropin-releasing hormone receptor pathway, Endothelin signaling pathway, and Inflammation mediated by chemokine and cytokine signaling pathway.


2021 ◽  
Author(s):  
Nana Yang ◽  
Qianghua Wang ◽  
Biao Ding ◽  
Yinging Gong ◽  
Yue Wu ◽  
...  

Abstract Background: The accumulation of ROS resulting from upregulated levels of oxidative stress is commonly implicated in preeclampsia (PE). Ferroptosis is a novel form of iron-dependent cell death instigated by lipid peroxidation likely plays important role in PE pathogenesis. This study aims to investigate expression profiles and functions of the ferroptosis-related genes (FRGs) in early- and late-onset preeclampsia.Methods: The gene expression data and clinical information were downloaded from GEO database. The “limma” R package was used for screening differentially expressed genes. GO(Gene Ontology), Kyoto Encyclopedia of Genes and Genomes(KEGG) and protein protein interaction (PPI) network analyses were conducted to investigate the bioinformatics functions and molecular interactions of significantly different FRGs. Quantitative real-time reverse transcriptase PCR was used to verify the expression of hub FRGs in PE.Results: A total number of 4,215 DEGs were identified between EOPE and preterm cases and 3,356 DEGs were found between EOPE and LOPE subtypes. 20 significantly different FRGs were identified in EOPE, while only 3 in LOPE. Functional enrichment analysis revealed that the differentially expressed FRGs was mainly involved in EOPE and enriched in hypoxia- and iron-related pathways, such as response to hypoxia, iron homeostasis and iron ion binding process. The PPI network analysis and verification by RT-qPCR resulted in the identification of the following six interesting FRGs: FTH1, HIF1A, FTL, IREB2, MAPK8 and PLIN2. Conclusions: EOPE and LOPE owned distinct underlying molecular mechanisms and ferroptosis may be mainly implicated in pathogenesis of EOPE. Further studies are necessary for deeper inquiry into placental ferroptosis and its role in the pathogenesis of EOPE.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yanhong Sun ◽  
Huijie Wei ◽  
Jian Chen ◽  
Pei Li ◽  
Qing Yang ◽  
...  

Certain members of the Actinopterygii class are known to exhibit sexual dimorphism (SD) that results in major phenotypic differences between male and female fishes of a species. One of the most common differences between the two sexes is in body weight, a factor with a high economic value in aquaculture. In this study, we used RNA sequencing (RNA-seq) to study the liver and brain transcriptomes of Ancherythroculter nigrocauda, a fish exhibiting SD. Females attain about fourfold body weight of males at sexual maturity. Sample clustering showed that both sexes were grouped well with their sex phenotypes. In addition, 2,395 and 457 differentially expressed genes (DEGs) were identified in the liver and brain tissues, respectively. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses predicted the association of PPAR signaling, cytochrome P450, and steroid hormone biosynthesis to the differences in sexual size. In addition, weighted gene co-expression network analyses (WGCNA) were conducted, and the green module was identified to be significantly correlated with sexual size dimorphism (SSD). Altogether, these results improve our understanding of the molecular mechanism underlying SSD in A. nigrocauda.


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