scholarly journals Reproductive Toxicity Induced By Benzo[a]pyrene Exposure: First Exploration Highlighting The Multi-stage Molecular Mechanism In Female Scallop Chlamys Farreri

2021 ◽  
Author(s):  
Ruiyi Xu ◽  
Luqing Pan ◽  
Yueyao Zhou ◽  
Zhongyuan Gao ◽  
Jingjing Miao ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Endocrine Disruption ◽  
Molecular Mechanisms ◽  
Reproductive Toxicity ◽  
Chlamys Farreri ◽  
Functional Enrichment ◽  
Expression Data ◽  
Single Strand Break ◽  
Toxic Mechanism ◽  
Multi Stage

Abstract Reproductive toxicity induced by Benzo[a]pyrene (B[a]P) exposure have received great ecotoxicological concerns. However, huge gaps on molecular mechanism still exist in bivalves. In this study, reproduction-related indicators during reproductive periods (proliferative, growth, mature, and spawn stage) were investigated in female scallops Chlamys farreri, which under gradient concentration of B[a]P at 0, 0.04, 0.4 and 4 μg/L. To elucidate the potential molecular mechanisms of reproductive toxicology, a multi-stage ovarian transcriptome analysis under 4 μg/L B[a]P exposure was also conducted. The results indicated that life-cycle exposure to 0.4 and 4 μg/L B[a]P had significantly decreased GSI and sex steroid levels. Even 0.04 μg/L B[a]P could play the wicked role on DNA integrity at mature and spawn stages. Ovarian histological sections showed the inhibitions on oocyte maturation and ovulation of B[a]P with dose-dependent effects. Through the functional enrichment analysis of DEGs from transcriptome data, 18 genes involved in endocrine disruption effects, DNA damage and repair, and oogenesis damage were selected and further determined by qRT-PCR. The down-regulate of steroidogenic and estrogen signaling pathways genes indicated the endocrine disruption mechanisms by B[a]P, which emphasized the functions of receptor independent and dependent pathways under B[a]P exposure. The variation of DNA single strand break and repair gene expressions implied there might exist the similar toxic mechanism with that in vertebrates. Gene expression data involved in cell cycle, apoptosis and cell adhesion exhibited the possibly toxic mechanisms of oogenesis caused by B[a]P. Taken together, this study is a pioneer to take advantage of genome-wide transcriptomic analysis and its corresponding reproductive indicators to explore the toxic mechanism under B[a]P exposure in bivalves. Meanwhile, some selected genes were firstly identified in bivalves, and the expression data might be useful in establishing new hypotheses and discovering new biomarkers for marine biomonitoring.

scholarly journals Analysis of potential genetic biomarkers and molecular mechanism of smoking-related postmenopausal osteoporosis using weighted gene co-expression network analysis and machine learning

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257343
Author(s):  
Shaoshuo Li ◽  
Baixing Chen ◽  
Hao Chen ◽  
Zhen Hua ◽  
Yang Shao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Machine Learning ◽  
Network Analysis ◽  
Postmenopausal Osteoporosis ◽  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Functional Enrichment ◽  
Support Vector ◽  
Hub Genes ◽  
Genetic Biomarkers

Objectives Smoking is a significant independent risk factor for postmenopausal osteoporosis, leading to genome variations in postmenopausal smokers. This study investigates potential biomarkers and molecular mechanisms of smoking-related postmenopausal osteoporosis (SRPO). Materials and methods The GSE13850 microarray dataset was downloaded from Gene Expression Omnibus (GEO). Gene modules associated with SRPO were identified using weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) analysis, and pathway and functional enrichment analyses. Feature genes were selected using two machine learning methods: support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF). The diagnostic efficiency of the selected genes was assessed by gene expression analysis and receiver operating characteristic curve. Results Eight highly conserved modules were detected in the WGCNA network, and the genes in the module that was strongly correlated with SRPO were used for constructing the PPI network. A total of 113 hub genes were identified in the core network using topological network analysis. Enrichment analysis results showed that hub genes were closely associated with the regulation of RNA transcription and translation, ATPase activity, and immune-related signaling. Six genes (HNRNPC, PFDN2, PSMC5, RPS16, TCEB2, and UBE2V2) were selected as genetic biomarkers for SRPO by integrating the feature selection of SVM-RFE and RF. Conclusion The present study identified potential genetic biomarkers and provided a novel insight into the underlying molecular mechanism of SRPO.

scholarly journals Comparative transcriptome profiling reveals cold stress responsiveness in two contrasting Chinese jujube cultivars

2020 ◽  
Author(s):  
Heying Zhou ◽  
Ying He ◽  
Yongsheng Zhu ◽  
Meiyu Li ◽  
Shuang Song ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Freezing Tolerance ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Transcriptome Profiling ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Freezing Stress ◽  
Comparative Transcriptome ◽  
Chinese Jujube

Abstract Background: Low temperature is a major factor influencing the growth and development of Chinese jujube ( Ziziphus jujuba Mill.) in cold winter and spring. Little is known about the molecular mechanisms enabling jujube to cope with different freezing stress conditions. To elucidate the freezing-related molecular mechanism, we conducted comparative transcriptome analysis between ‘Dongzao’ (low freezing tolerance cultivar) and ‘Jinsixiaozao’ (high freezing tolerance cultivar) using RNA-Seq. Results: More than 20,000 genes were detected at chilling (4°C) and freezing (-10°C, -20°C, -30°C and -40°C) stress between the two cultivars. The numbers of differentially expressed genes (DEGs) between the two cultivars were 1831, 2030, 1993, 1845 and 2137 under the five treatments. Functional enrichment analysis suggested that the metabolic pathway, response to stimulus and catalytic activity were significantly enriched under stronger freezing stress. Among the DEGs, nine participated in the Ca 2+ signal pathway, thirty-two were identified to participate in sucrose metabolism, and others were identified to participate in the regulation of ROS, plant hormones and antifreeze proteins. In addition, important transcription factors ( WRKY , AP2 / ERF , NAC and bZIP ) participating in freezing stress were activated under different degrees of freezing stress. Conclusions: Our research first provides a more comprehensive understanding of DEGs involved in freezing stress at the transcriptome level in two Z. jujuba cultivars with different freezing tolerances. These results may help to elucidate the molecular mechanism of freezing tolerance in jujube and also provides new insights and candidate genes for genetically enhancing freezing stress tolerance.

scholarly journals CENPL, ISG20L2, LSM4 and MRPL3 Are Four Novel Hub Genes Involved in Breast Cancer Development and Progression

2020 ◽  
Author(s):  
Jinbao Yin ◽  
Chen Lin ◽  
Meng jiang ◽  
Xinbing Tang ◽  
Danlin Xie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Network Analysis ◽  
Candidate Genes ◽  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Rank Aggregation ◽  
Functional Enrichment ◽  
Hub Genes ◽  
Ppi Networks ◽  
Kaplan Meier

Abstract BackgroundAs a highly prevalent tumor disease worldwide, Further elucidation of the molecular mechanisms of the occurrence, development and prognosis of breast cancer remain an urgent need. Identifying hub genes involved in these pathogenesis and progression can potentially help to unveil its mechanism and provide novel diagnostic and prognostic markers for breast cancer.MethodsIn this study, we systematically integrated multiple bioinformatic methods, including robust rank aggregation (RRA), functional enrichment analysis, protein-protein interaction (PPI) networks construction and analysis, weighted gene co-expression network analysis (WGCNA), ROC and Kaplan-Meier analyses, DNA methylation analyses and genomic mutation analyses, GSEA and GSVA, based on ten mRNA datasets to identify and investigate novel hub genes involved in breast cancer. In parallel, RNA in situ detection technology was applied to validate those novel hub gene.ResultsEZH2 was recognized as a key gene by PPI network analysis. CENPL, ISG20L2, LSM4 and MRPL3 were identified as four novel hub genes through the WGCNA analysis and literate search. Among those five hub genes, many studies on EZH2 gene in breast cancer have been reported, but no studies are related to the roles of CENPL, ISG20L2, MRPL3 and LSM4 in breast cancer. These novel four hub genes were up-regulated in breast cancer tissues and associated with tumor progression. ROC and Kaplan-Meier indicated these four hub genes all showed good diagnostic performance and prognostic values for breast cancer. The preliminary analysis revealed those novel hub genes are four potentially candidate genes for further exploring the molecular mechanism of breast cancer.ConclusionWe identify four novel hub genes (CENPL, ISG20L2, MRPL3, and LSM4) that are likely playing key roles in the molecular mechanism of occurrence and development of breast cancer. Those hub genes are four potentially candidate genes served as promising candidate diagnostic biomarkers and prognosis predictors for breast cancer, and their exact functional mechanisms in breast cancer deserve further in-depth study.

scholarly journals Biomarker MicroRNAs for Diagnosis of Oral Squamous Cell Carcinoma Identified Based on Gene Expression Data and MicroRNA-mRNA Network Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Hui Zhang ◽  
Tangxin Li ◽  
Linqing Zheng ◽  
Xiangya Huang
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Gene Expression Data ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Biomarker Discovery ◽  
Functional Enrichment ◽  
Expression Data

Oral squamous cell carcinoma is one of the most malignant tumors with high mortality rate worldwide. Biomarker discovery is critical for early diagnosis and precision treatment of this disease. MicroRNAs are small noncoding RNA molecules which often regulate essential biological processes and are good candidates for biomarkers. By integrative analysis of both the cancer-associated gene expression data and microRNA-mRNA network, miR-148b-3p, miR-629-3p, miR-27a-3p, and miR-142-3p were screened as novel diagnostic biomarkers for oral squamous cell carcinoma based on their unique regulatory abilities in the network structure of the conditional microRNA-mRNA network and their important functions. These findings were confirmed by literature verification and functional enrichment analysis. Future experimental validation is expected for the further investigation of their molecular mechanisms.

scholarly journals Comparative transcriptome profiling reveals cold stress responsiveness in two contrasting Chinese jujube cultivars

2020 ◽  
Author(s):  
Heying Zhou ◽  
Ying He ◽  
Yongsheng Zhu ◽  
Meiyu Li ◽  
Shuang Song ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Freezing Tolerance ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Transcriptome Profiling ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Freezing Stress ◽  
Comparative Transcriptome ◽  
Chinese Jujube

Abstract Background: Low temperature is a major factor influencing the growth and development of Chinese jujube (Ziziphus jujuba Mill.) in cold winter and spring. Little is known about the molecular mechanisms enabling jujube to cope with different freezing stress conditions. To elucidate the freezing-related molecular mechanism, we conducted comparative transcriptome analysis between ‘Dongzao’ (low freezing tolerance cultivar) and ‘Jinsixiaozao’ (high freezing tolerance cultivar) using RNA-Seq. Results: More than 20,000 genes were detected at chilling (4°C) and freezing (-10°C, -20°C, -30°C and -40°C) stress between the two cultivars. The numbers of differentially expressed genes (DEGs) between the two cultivars were 1831, 2030, 1993, 1845 and 2137 under the five treatments. Functional enrichment analysis suggested that the metabolic pathway, response to stimulus and catalytic activity were significantly enriched under stronger freezing stress. Among the DEGs, nine participated in the Ca2+ signal pathway, thirty-two were identified to participate in sucrose metabolism, and others were identified to participate in the regulation of ROS, plant hormones and antifreeze proteins. In addition, important transcription factors (WRKY, AP2/ERF, NAC and bZIP) participating in freezing stress were activated under different degrees of freezing stress. Conclusions: Our research first provides a more comprehensive understanding of DEGs involved in freezing stress at the transcriptome level in two Z. jujuba cultivars with different freezing tolerances. These results may help to elucidate the molecular mechanism of freezing tolerance in jujube and also provides new insights and candidate genes for genetically enhancing freezing stress tolerance.

Systems Biology Approaches Reveal a Multi-stress Responsive WRKY Transcription Factor and Stress Associated Gene Co-expression Networks in Chickpea

2019 ◽  
Vol 14 (7) ◽  
pp. 591-601 ◽  
Author(s):  
Aravind K. Konda ◽  
Parasappa R. Sabale ◽  
Khela R. Soren ◽  
Shanmugavadivel P. Subramaniam ◽  
Pallavi Singh ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Wrky Transcription Factor ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Callose Deposition ◽  
Significant Probability

Background: Chickpea is a nutritional rich premier pulse crop but its production encounters setbacks due to various stresses and understanding of molecular mechanisms can be ascribed foremost importance. Objective: The investigation was carried out to identify the differentially expressed WRKY TFs in chickpea in response to herbicide stress and decipher their interacting partners. Methods: For this purpose, transcriptome wide identification of WRKY TFs in chickpea was done. Behavior of the differentially expressed TFs was compared between other stress conditions. Orthology based cofunctional gene networks were derived from Arabidopsis. Gene ontology and functional enrichment analysis was performed using Blast2GO and STRING software. Gene Coexpression Network (GCN) was constructed in chickpea using publicly available transcriptome data. Expression pattern of the identified gene network was studied in chickpea-Fusarium interactions. Results: A unique WRKY TF (Ca_08086) was found to be significantly (q value = 0.02) upregulated not only under herbicide stress but also in other stresses. Co-functional network of 14 genes, namely Ca_08086, Ca_19657, Ca_01317, Ca_20172, Ca_12226, Ca_15326, Ca_04218, Ca_07256, Ca_14620, Ca_12474, Ca_11595, Ca_15291, Ca_11762 and Ca_03543 were identified. GCN revealed 95 hub genes based on the significant probability scores. Functional annotation indicated role in callose deposition and response to chitin. Interestingly, contrasting expression pattern of the 14 network genes was observed in wilt resistant and susceptible chickpea genotypes, infected with Fusarium. Conclusion: This is the first report of identification of a multi-stress responsive WRKY TF and its associated GCN in chickpea.

Regulation of microRNAs in Inflammation-Associated Colorectal Cancer: A Mechanistic Approach

2020 ◽  
Vol 20 ◽  
Author(s):  
Sridhar Muthusami ◽  
Ilangovan Ramachandran ◽  
Sneha Krishnamoorthy ◽  
Yuvaraj Sambandam ◽  
Satish Ramalingam ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Colorectal Carcinogenesis ◽  
Model Systems ◽  
Necrosis Factor Alpha ◽  
Multi Stage ◽  
Mechanistic Approach ◽  
Tnf Α ◽  
Factor Alpha

: The development of colorectal cancer (CRC) is a multi-stage process. The inflammation of the colon as in inflammatory bowel disease (IBD) such as ulcerative colitis (UC) or Crohn’s disease (CD) is often regarded as the initial trigger for the development of CRC. Many cytokines such as tumor necrosis factor alpha (TNF-α) and several interleukins (ILs) are known to exert proinflammatory actions, and inflammation initiates or promotes tumorigenesis of various cancers, including CRC through differential regulation of microRNAs (miRNAs/miRs). miRNAs can be oncogenic miRNAs (oncomiRs) or anti-oncomiRs/tumor suppressor miRNAs, and they play key roles during colorectal carcinogenesis. However, the functions and molecular mechanisms of regulation of miRNAs involved in inflammation-associated CRC are still anecdotal and largely unknown. Consolidating the published results and offering perspective solutions to circumvent CRC, the current review is focused on the role of miRNAs and their regulation in the development of CRC. We have also discussed the model systems adapted by researchers to delineate the role of miRNAs in inflammation-associated CRC.

scholarly journals Developmental cannabidiol exposure increases anxiety and modifies genome-wide brain DNA methylation in adult female mice

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Nicole M. Wanner ◽  
Mathia Colwell ◽  
Chelsea Drown ◽  
Christopher Faulk
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Coat Color ◽  
Brain Regions ◽  
Functional Enrichment ◽  
Positive Effects ◽  
Genome Wide ◽  
Nulliparous Female ◽  
The Impact ◽  
The Brain

Abstract Background Use of cannabidiol (CBD), the primary non-psychoactive compound found in cannabis, has recently risen dramatically, while relatively little is known about the underlying molecular mechanisms of its effects. Previous work indicates that direct CBD exposure strongly impacts the brain, with anxiolytic, antidepressant, antipsychotic, and other effects being observed in animal and human studies. The epigenome, particularly DNA methylation, is responsive to environmental input and can direct persistent patterns of gene regulation impacting phenotype. Epigenetic perturbation is particularly impactful during embryogenesis, when exogenous exposures can disrupt critical resetting of epigenetic marks and impart phenotypic effects lasting into adulthood. The impact of prenatal CBD exposure has not been evaluated; however, studies using the psychomimetic cannabinoid Δ9-tetrahydrocannabinol (THC) have identified detrimental effects on psychological outcomes in developmentally exposed adult offspring. We hypothesized that developmental CBD exposure would have similar negative effects on behavior mediated in part by the epigenome. Nulliparous female wild-type Agouti viable yellow (Avy) mice were exposed to 20 mg/kg CBD or vehicle daily from two weeks prior to mating through gestation and lactation. Coat color shifts, a readout of DNA methylation at the Agouti locus in this strain, were measured in F1 Avy/a offspring. Young adult F1 a/a offspring were then subjected to tests of working spatial memory and anxiety/compulsive behavior. Reduced-representation bisulfite sequencing was performed on both F0 and F1 cerebral cortex and F1 hippocampus to identify genome-wide changes in DNA methylation for direct and developmental exposure, respectively. Results F1 offspring exposed to CBD during development exhibited increased anxiety and improved memory behavior in a sex-specific manner. Further, while no significant coat color shift was observed in Avy/a offspring, thousands of differentially methylated loci (DMLs) were identified in both brain regions with functional enrichment for neurogenesis, substance use phenotypes, and other psychologically relevant terms. Conclusions These findings demonstrate for the first time that despite positive effects of direct exposure, developmental CBD is associated with mixed behavioral outcomes and perturbation of the brain epigenome.

Cellular and molecular mechanisms of statins: an update on pleiotropic effects

2015 ◽  
Vol 129 (2) ◽  
pp. 93-105 ◽  
Author(s):  
Mamoru Satoh ◽  
Yuji Takahashi ◽  
Tsuyoshi Tabuchi ◽  
Yoshitaka Minami ◽  
Makiko Tamada ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Chronic Inflammation ◽  
Molecular Mechanism ◽  
Coronary Atherosclerosis ◽  
Molecular Mechanisms ◽  
Cell Injury ◽  
Plaque Instability ◽  
Beneficial Effects ◽  
Reductase Inhibitors ◽  
Artery Disease

Coronary artery disease (CAD) is the leading cause of death worldwide. The efficacy and safety of statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) in primary and secondary prevention of CAD are confirmed in several large studies. It is well known that statins have some pleiotropic, anti-atherosclerotic effects. We review the molecular mechanisms underlying the beneficial effects of statins revealed in recently published studies. Endothelial cell injury is regarded as the classic stimulus for the development of atherosclerotic lesions. In addition, the inflammatory process plays an important role in the aetiology of atherosclerosis. In particular, chronic inflammation plays a key role in coronary artery plaque instability and subsequent occlusive thrombosis. Our previous reports and others have demonstrated beneficial effects of statins on endothelial dysfunction and chronic inflammation in CAD. A better understanding of the molecular mechanism underlying the effectiveness of statins against atherosclerosis may provide a novel therapeutic agent for the treatment of coronary atherosclerosis. The present review summarizes the cellular and molecular mechanism of statins against coronary atherosclerosis.

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