Ocean Acidification Triggers Cell Signaling, Suppress Immune and Calcification in the Pacific Oyster Larvae

Elevated carbon dioxide levels in ocean waters, an anthropogenic stressor, can alter the chemical equilibrium of seawater through a process called ocean acidification (OA). The resultant reduction of pH can be detrimental during the early developmental stages of the commercially important edible Pacific oyster Crassostrea gigas; the ability of larvae to join a population is likely to be compromised by declining ocean pH. Given this threat, it is important to study the molecular mechanisms that these organisms use to overcome OA stress at the gene expression level. Here, we performed transcriptome profiling in oyster larvae following exposure to ambient (8.1) and reduced (7.4) pH during the pre-settlement growth period (i.e., 18 d post fertilization) using RNA-seq with Illumina sequencing technology. In total, 1,808 differentially expressed genes (DEGs) were identified, 1,410 of which were matched by BLAST against the Swiss-Prot database. Gene ontology classification showed that most of these DEGs were related to ribosomal, calcium ion binding, cell adhesion and apoptotic processes. Pathway enrichment analysis revealed that low pH (7.4) enhanced energy production and organelle biogenesis but prominently suppressed several immune response pathways. Moreover, activation of the MAPK signaling pathway was observed along with inhibition of the Wnt, VEGF, and ErbB pathways, highlighting the fact that the initiation of stress responses is given priority over larval development or shell growth when the larvae cope with low pH. In conclusion, our study demonstrated a unique gene expression profiling approach in studying oyster larval responses to OA, which not only provides comprehensive insights into the mechanisms underlying oyster tolerance to CO2-driven decreases in ocean pH but also supplies a valuable genomic resource for further studies in this species.

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Variation in brachiopod microstructure and isotope geochemistry under low pH–ocean acidification–conditions

10.5194/bg-2018-332 ◽

2018 ◽

Author(s):

Facheng Ye ◽

Hana Jurikova ◽

Lucia Angiolini ◽

Uwe Brand ◽

Gaia Crippa ◽

...

Keyword(s):

Stable Isotope ◽

Ocean Acidification ◽

Isotope Geochemistry ◽

Shell Growth ◽

Low Ph ◽

Secondary Layer ◽

Ph Conditions ◽

One Year ◽

The Impact ◽

Δ13c And Δ18o

Abstract. Throughout the last few decades and in the near future CO2–induced ocean acidification is potentially a big threat to marine calcite-shelled animals (e.g., brachiopods, bivalves, corals and gastropods). Despite the great number of studies focusing on the effects of acidification on shell growth, metabolism, shell dissolution and shell repair, the consequences on biomineral formation remain poorly understood, and only few studies addressed contemporarily the impact of acidification on shell microstructure and geochemistry. In this study, a detailed microstructure and stable isotope geochemistry investigation was performed on nine adult brachiopod specimens of Magellania venosa (Dixon, 1789), grown in the natural environment as well as in controlled culturing experiments at different pH conditions (ranging 7.35 to 8.15 ± 0.05) over different time intervals (214 to 335 days). Details of shell microstructural features, such as thickness of the primary layer, density and size of endopunctae and morphology of the basic structural unit of the secondary layer were analysed using scanning electron microscopy (SEM). Stable isotope compositions (δ13C and δ18O) were tested from the secondary shell layer along shell ontogenetic increments in both dorsal and ventral valves. Based on our comprehensive dataset, we observed that, under low pH conditions, M. venosa produced a more organic-rich shell with higher density of and larger endopunctae, and smaller secondary layer fibres, when subjected to about one year of culturing. Also, increasingly negative δ13C and δ18O values are recorded by the shell produced during culturing and are related to the CO2–source in the culture setup. Both the microstructural changes and the stable isotope results are similar to observations on brachiopods from the fossil record and strongly support the value of brachiopods as robust archives of proxies for studying ocean acidification events in the geologic past.

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Bioinformatic analysis identifies potential biomarkers and therapeutic targets of septic-shock-associated acute kidney injury

Hereditas ◽

10.1186/s41065-021-00176-y ◽

2021 ◽

Vol 158 (1) ◽

Author(s):

Yun Tang ◽

Xiaobo Yang ◽

Huaqing Shu ◽

Yuan Yu ◽

Shangwen Pan ◽

...

Keyword(s):

Gene Expression ◽

Septic Shock ◽

Acute Kidney Injury ◽

Molecular Mechanisms ◽

Therapeutic Targets ◽

Kidney Injury ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Blood Samples ◽

Potential Biomarkers

Abstract Background Sepsis and septic shock are life-threatening diseases with high mortality rate in intensive care unit (ICU). Acute kidney injury (AKI) is a common complication of sepsis, and its occurrence is a poor prognostic sign to septic patients. We analyzed co-differentially expressed genes (co-DEGs) to explore relationships between septic shock and AKI and reveal potential biomarkers and therapeutic targets of septic-shock-associated AKI (SSAKI). Methods Two gene expression datasets (GSE30718 and GSE57065) were downloaded from the Gene Expression Omnibus (GEO). The GSE57065 dataset included 28 septic shock patients and 25 healthy volunteers and blood samples were collected within 0.5, 24 and 48 h after shock. Specimens of GSE30718 were collected from 26 patients with AKI and 11 control patents. AKI-DEGs and septic-shock-DEGs were identified using the two datasets. Subsequently, Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate molecular mechanisms of DEGs. We also evaluated co-DEGs and corresponding predicted miRNAs involved in septic shock and AKI. Results We identified 62 DEGs in AKI specimens and 888, 870, and 717 DEGs in septic shock blood samples within 0.5, 24 and 48 h, respectively. The hub genes of EGF and OLFM4 may be involved in AKI and QPCT, CKAP4, PRKCQ, PLAC8, PRC1, BCL9L, ATP11B, KLHL2, LDLRAP1, NDUFAF1, IFIT2, CSF1R, HGF, NRN1, GZMB, and STAT4 may be associated with septic shock. Besides, co-DEGs of VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 coupled with corresponding predicted miRNAs, especially miR-29b-3p, miR-152-3p, and miR-223-3p may be regarded as promising targets for the diagnosis and treatment of SSAKI in the future. Conclusions Septic shock and AKI are related and VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 genes are significantly associated with novel biomarkers involved in the occurrence and development of SSAKI.

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Anticancer Effects of Emodin on HepG2 Cell: Evidence from Bioinformatic Analysis

BioMed Research International ◽

10.1155/2019/3065818 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Rui-sheng Zhou ◽

Xiong-Wen Wang ◽

Qin-feng Sun ◽

Zeng Jie Ye ◽

Jian-wei Liu ◽

...

Keyword(s):

Signaling Pathway ◽

Hepg2 Cells ◽

Molecular Mechanisms ◽

Mapk Signaling ◽

Ion Concentration ◽

Receptor Interaction ◽

Pathway Enrichment Analysis ◽

Mrna Levels ◽

Hub Genes ◽

Positive Regulation

Hepatocellular carcinoma (HCC) is a primary cause of cancer-related death in the world. Despite the fact that there are many methods to treat HCC, the 5-year survival rate of HCC is still at a low level. Emodin can inhibit the growth of HCC cells invitroand invivo. However, the gene regulation of emodin in HCC has not been well studied. In our research, RNA sequencing technology was used to identify the differentially expressed genes (DEGs) in HepG2 cells induced by emodin. A total of 859 DEGs were identified, including 712 downregulated genes and 147 upregulated genes in HepG2 cells treated with emodin. We used DAVID for function and pathway enrichment analysis. The protein-protein interaction (PPI) network was constructed using STRING, and Cytoscape was used for module analysis. The enriched functions and pathways of the DEGs include positive regulation of apoptotic process, structural molecule activity and lipopolysaccharide binding, protein digestion and absorption, ECM-receptor interaction, complement and coagulation cascades, and MAPK signaling pathway. 25 hub genes were identified and pathway analysis revealed that these genes were mainly enriched in neuropeptide signaling pathway, inflammatory response, and positive regulation of cytosolic calcium ion concentration. Survival analysis showed that LPAR6, C5, SSTR5, GPR68, and P2RY4 may be involved in the molecular mechanisms of emodin therapy for HCC. A quantitative real-time PCR (qRT-PCR) assay showed that the mRNA levels of LPAR6, C5, SSTR5, GPR68, and P2RY4 were significantly decreased in HepG2 cells treated with emodin. In conclusion, the identified DEGs and hub genes in the present study provide new clues for further researches on the molecular mechanisms of emodin.

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Whole transcriptome analysis of adrenal glands from prenatal glucocorticoid programmed hypertensive rodents

Scientific Reports ◽

10.1038/s41598-020-75652-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Sujeenthar Tharmalingam ◽

Sandhya Khurana ◽

Alyssa Murray ◽

Jeremy Lamothe ◽

T. C. Tai

Keyword(s):

Gene Expression ◽

Circadian Rhythm ◽

Transcriptome Analysis ◽

Molecular Mechanisms ◽

Adrenal Glands ◽

Genetic Model ◽

Pathway Enrichment Analysis ◽

Wistar Kyoto ◽

Whole Transcriptome Analysis ◽

Whole Transcriptome

Abstract Prenatal glucocorticoid exposure is associated with the development of hypertension in adults. We have previously demonstrated that antenatal dexamethosone (DEX) administration in Wistar-Kyoto dams results in offspring with increased blood pressure coupled with elevated plasma epinephrine levels. In order to elucidate the molecular mechanisms responsible for prenatal DEX-mediated programming of hypertension, a whole-transcriptome analysis was performed on DEX programmed WKY male adrenal glands using the Rat Gene 2.0 microarray. Differential gene expression (DEG) analysis of DEX-exposed offspring compared with saline-treated controls revealed 142 significant DEGs (109 upregulated and 33 downregulated genes). DEG pathway enrichment analysis demonstrated that genes involved in circadian rhythm signaling were most robustly dysregulated. RT-qPCR analysis confirmed the increased expression of circadian genes Bmal1 and Npas2, while Per2, Per3, Cry2 and Bhlhe41 were significantly downregulated. In contrast, gene expression profiling of Spontaneously Hypertensive (SHR) rats, a genetic model of hypertension, demonstrated decreased expression of Bmal1 and Npas2, while Per1, Per2, Per3, Cry1, Cry2, Bhlhe41 and Csnk1D were all upregulated compared to naïve WKY controls. Taken together, this study establishes that glucocorticoid programmed adrenals have impaired circadian signaling and that changes in adrenal circadian rhythm may be an underlying molecular mechanism responsible for the development of hypertension.

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Characteristic Features of the Transcriptome in a Rat Strain with Audiogenic Epilepsy

KnE Life Sciences ◽

10.18502/kls.v7i1.10140 ◽

2022 ◽

Author(s):

Lyubov N. Chuvakova ◽

Sergey Yu. Funikov ◽

Artem I. Davletshin ◽

Irina B. Fedotova ◽

Mikhail B. Evgen'ev ◽

...

Keyword(s):

Gene Expression ◽

Dna Repair ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Mapk Signaling ◽

Repair System ◽

Audiogenic Epilepsy ◽

Rat Strain ◽

Characteristic Features

Audiogenic epilepsy (AE), developing in rodent strains in response to sound, is widely used as the model of generalized convulsive epilepsy, while the molecular mechanisms determining AE are currently poorly understood. The brain region that is crucial for AE development isthe inferior and superior colliculi (IC, SC). We compared IC-SC gene expression profiles in rats with different AE susceptibility using transcriptome analysis.The transcriptomes were obtained from the IC-SC of Wistar rats (with no AE), Krushinsky-Molodkina (KM) strain rats (100% AE susceptible), and ”0” strain rats (with no AE) selected from F2 KM x Wistar hybrids for AE absence. KM gene expression displayed characteristic differences inboth of the strains that were not susceptible to AE. There was increased expression of a number of genes responsible for positive regulation of the MAPK signaling cascade, as well as of genes responsible for the production of interferon and several other cytokines. An increase in the expression levels of theTTR gene was found in KM rats, as well as significantly lower expression of the Msh3 gene (involved in post-replicative DNA repair systems). AE was also describedin the 101/HY mouse strain with a mutation in the locus controlling DNA repair. The DNA repair system defects could be the primary factor leading to the accumulation of mutations, which, in turn, promote AE. Keywords: udiogenic seizure, KM strain, transcriptome, TTR gene, Msh3 gene, DNA repair

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Different RNA splicing mechanisms contribute to diverse infective outcome of classical swine fever viruses of differing virulence: insights from the deep sequencing data in swine umbilical vein endothelial cells

PeerJ ◽

10.7717/peerj.2113 ◽

2016 ◽

Vol 4 ◽

pp. e2113 ◽

Cited By ~ 4

Author(s):

Pengbo Ning ◽

Yulu Zhou ◽

Wulong Liang ◽

Yanming Zhang

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Rna Splicing ◽

Molecular Mechanisms ◽

Computational Study ◽

Umbilical Vein ◽

Classical Swine Fever ◽

Pathway Enrichment Analysis ◽

Splicing Regulation ◽

Umbilical Vein Endothelial Cells

Molecular mechanisms underlying RNA splicing regulation in response to viral infection are poorly understood. Classical swine fever (CSF), one of the most economically important and highly contagious swine diseases worldwide, is caused by classical swine fever virus (CSFV). Here, we used high-throughput sequencing to obtain the digital gene expression (DGE) profile in swine umbilical vein endothelial cells (SUVEC) to identify different response genes for CSFV by using both Shimen and C strains. The numbers of clean tags obtained from the libraries of the control and both CSFV-infected libraries were 3,473,370, 3,498,355, and 3,327,493 respectively. In the comparison among the control, CSFV-C, and CSFV-Shimen groups, 644, 158, and 677 differentially expressed genes (DEGs) were confirmed in the three groups. Pathway enrichment analysis showed that many of these DEGs were enriched in spliceosome, ribosome, proteasome, ubiquitin-mediated proteolysis, cell cycle, focal adhesion, Wnt signalling pathway, etc., where the processes differ between CSFV strains of differing virulence. To further elucidate important mechanisms related to the differential infection by the CSFV Shimen and C strains, we identified four possible profiles to assess the significantly expressed genes only by CSFV Shimen or CSFV C strain. GO analysis showed that infection with CSFV Shimen and C strains disturbed ‘RNA splicing’ of SUVEC, resulting in differential ‘gene expression’ in SUVEC. Mammalian target of rapamycin (mTOR) was identified as a significant response regulator contributed to impact on SUVEC function for CSFV Shimen. This computational study suggests that CSFV of differing virulence could induce alterations in RNA splicing regulation in the host cell to change cell metabolism, resulting in acute haemorrhage and pathological damage or infectious tolerance.

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Bioinformatics Analysis Reveals the Potential Diagnostic Biomarkers for Abdominal Aortic Aneurysm

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.656263 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xinsheng Xie ◽

En ci Wang ◽

Dandan Xu ◽

Xiaolong Shu ◽

Yu fei Zhao ◽

...

Keyword(s):

Gene Expression ◽

Molecular Mechanisms ◽

Bioinformatics Analysis ◽

Inflammatory Responses ◽

Expression Profiles ◽

Enrichment Analysis ◽

Aortic Aneurysms ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Abdominal Aortic

Objectives: Abdominal aortic aneurysms (AAAs) are associated with high mortality rates. The genes and pathways linked with AAA remain poorly understood. This study aimed to identify key differentially expressed genes (DEGs) linked to the progression of AAA using bioinformatics analysis.Methods: Gene expression profiles of the GSE47472 and GSE57691 datasets were acquired from the Gene Expression Omnibus (GEO) database. These datasets were merged and normalized using the “sva” R package, and DEGs were identified using the limma package in R. The functions of these DEGs were assessed using Cytoscape software. We analyzed the DEGs using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Protein–protein interaction networks were assembled using Cytoscape, and crucial genes were identified using the Cytoscape plugin, molecular complex detection. Data from GSE15729 and GSE24342 were also extracted to verify our findings.Results: We found that 120 genes were differentially expressed in AAA. Genes associated with inflammatory responses and nuclear-transcribed mRNA catabolic process were clustered in two gene modules in AAA. The hub genes of the two modules were IL6, RPL21, and RPL7A. The expression levels of IL6 correlated positively with RPL7A and negatively with RPL21. The expression of RPL21 and RPL7A was downregulated, whereas that of IL6 was upregulated in AAA.Conclusions: The expression of RPL21 or RPL7A combined with IL6 has a diagnostic value for AAA. The novel DEGs and pathways identified herein might provide new insights into the underlying molecular mechanisms of AAA.

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Network Pharmacology Identifies the Mechanisms of Sang-Xing-Zhi-Ke-Fang against Pharyngitis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/2421916 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Yinhe Deng ◽

Quanjiang Li ◽

Menglin Li ◽

Tiantian Han ◽

Guixian Li ◽

...

Keyword(s):

Signaling Pathway ◽

Influenza A ◽

Molecular Mechanisms ◽

Mapk Signaling ◽

Venn Diagram ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Ras Signaling ◽

Clinical Effects ◽

Overlapping Genes

Background. Sang-Xing-Zhi-Ke-Fang (SXZKF) demonstrates good therapeutic effect against pharyngitis. Nevertheless, the pharmacological mechanism underlying its effectiveness is still unclear. Objective. To investigate the underlying mechanisms of SXZKF against pharyngitis using network pharmacology method. Methods. Bioactive ingredients of SXZKF were collected and screened using published literature and two public databases. Using four public databases, the overlapping genes between these bioactive compound-related and pharyngitis-related genes were identified by Venn diagram. Protein-protein interaction (PPI) was obtained using “Search Tool for the Retrieval of Interacting Genes (STRING)” database. “Database for Annotation, Visualization, and Integrated Discovery ver. 6.8 (DAVID 6.8)” was used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to explore the molecular mechanisms of SXZKF against pharyngitis. Finally, Cytoscape 3.7.2 software was used to construct and visualize the networks. Result. A total of 102 bioactive compounds were identified. Among them, 886 compounds-related and 6258 pharyngitis-related genes were identified, including 387 overlapping genes. Sixty-three core targets were obtained, including ALB, PPARγ, MAPK3, EGF, and PTGS2. Signaling pathways closely related to mechanisms of SXZKF for pharyngitis were identified, including serotonergic synapse, VEGF signaling pathway, Fc epsilon RI signaling pathway, Ras signaling pathway, MAPK signaling pathway, and influenza A. Conclusion. This is the first identification of in-depth study of SXZKF against pharyngitis using network pharmacology. This new evidence could be informative in providing new support on the clinical effects of SXZKF on pharyngitis and for the development of personalized medicine for pharyngitis.

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Unraveling reno-protective effects of SGLT2 inhibition in human proximal tubular cells

AJP Renal Physiology ◽

10.1152/ajprenal.00431.2018 ◽

2019 ◽

Vol 316 (3) ◽

pp. F449-F462 ◽

Cited By ~ 13

Author(s):

Markus Pirklbauer ◽

Ramona Schupart ◽

Lisa Fuchs ◽

Petra Staudinger ◽

Ulrike Corazza ◽

...

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Cell Lines ◽

Molecular Mechanisms ◽

Mrna Level ◽

Pathway Enrichment Analysis ◽

Protective Effects ◽

Proximal Tubular ◽

Pt Cell ◽

Tgf Β1

Large clinical trials demonstrated that SGLT2 inhibitors (SGLT2i) slow the progression of kidney function decline in type 2 diabetes. Because the underlying molecular mechanisms are largely unknown, we studied the effects of SGLT2i on gene expression in two human proximal tubular (PT) cell lines under normoglycemic conditions, utilizing two SGLT2i, namely empagliflocin and canagliflocin. Genome-wide expression analysis did not reveal substantial differences between these two SGLT2i. Microarray hybridization analysis identified 94 genes that were both upregulated by TGF-β1 and downregulated by either of the two SGLT2i in HK-2 and RPTEC/TERT1 (renal proximal tubular epithelial cells/telomerase reverse transcriptase 1) cells. Extracellular matrix organization showed the highest significance in pathway enrichment analysis. Differential gene expression of three annotated genes of interest within this pathway was verified on mRNA level in both cell lines. Whereas TGF-β1 induced mRNA expression of thrombospondin 1 (THBS1; 4.3-fold), tenascin C (TNC; 8-fold), and platelet-derived growth factor subunit B (PDGF-B; 4.2-fold), SGLT2i downregulated basal mRNA expression of THBS1 (0.2-fold), TNC (0.5 fold), and PDGF-B (0.6-fold). Administration of SGLT2i in the presence of TGF-β1 resulted in a significant inhibition of TGF-β1-induced THBS1 and TNC mRNA expression and TGF-β1-induced THBS1, TNC, and PDGF-BB protein expression. We conclude that SGLT2i block basal and TGF-β1-induced expression of key mediators of renal fibrosis and kidney disease progression in two independent human PT cell lines.

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Identification and Verification of Core Genes in Colorectal Cancer

BioMed Research International ◽

10.1155/2020/8082697 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Houxi Xu ◽

Yuzhu Ma ◽

Jinzhi Zhang ◽

Jialin Gu ◽

Xinyue Jing ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Malignant Neoplasm ◽

Gene Expression Profiles ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Core Genes

Colorectal cancer, a malignant neoplasm that occurs in the colorectal mucosa, is one of the most common types of gastrointestinal cancer. Colorectal cancer has been studied extensively, but the molecular mechanisms of this malignancy have not been characterized. This study identified and verified core genes associated with colorectal cancer using integrated bioinformatics analysis. Three gene expression profiles (GSE15781, GSE110223, and GSE110224) were downloaded from the Gene Expression Omnibus (GEO) databases. A total of 87 common differentially expressed genes (DEGs) among GSE15781, GSE110223, and GSE110224 were identified, including 19 upregulated genes and 68 downregulated genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed for common DEGs using clusterProfiler. These common DEGs were significantly involved in cancer-associated functions and signaling pathways. Then, we constructed protein-protein interaction networks of these common DEGs using Cytoscape software, which resulted in the identification of the following 10 core genes: SST, PYY, CXCL1, CXCL8, CXCL3, ZG16, AQP8, CLCA4, MS4A12, and GUCA2A. Analysis using qRT-PCR has shown that SST, CXCL8, and MS4A12 were significant differentially expressed between colorectal cancer tissues and normal colorectal tissues (P<0.05). Gene Expression Profiling Interactive Analysis (GEPIA) overall survival (OS) has shown that low expressions of AQP8, ZG16, CXCL3, and CXCL8 may predict poor survival outcome in colorectal cancer. In conclusion, the core genes identified in this study contributed to the understanding of the molecular mechanisms involved in colorectal cancer development and may be targets for early diagnosis, prevention, and treatment of colorectal cancer.

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