RESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) has a poor long-term prognosis. The competition of circular RNAs (circRNAs) with endogenous RNA is a novel tool for predicting HCC prognosis. Based on the alterations of circRNA regulatory networks, the analysis of gene modules related to HCC is feasible. METHODS: Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC. Gene function, pathway, and protein interaction analyses were performed for the differentially expressed genes (DEGs) in this regulatory network. In the protein-protein interaction network, hub genes were identified and subjected to regression analysis, producing an optimized four-gene signature for prognostic risk stratification in HCC patients. Anti-HCC drugs were excavated by assessing the DEGs between the low- and high-risk groups. A circRNA-microRNA-hub gene subnetwork was constructed, in which three hallmark genes, KIF4A, CCNA2, and PBK, were subjected to functional enrichment analysis. RESULTS: A four-gene signature (KIF4A, CCNA2, PBK, and ZWINT) that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas (TCGA) cohort and International Cancer Genome Consortium (ICGC) cohort was developed. CDK inhibitors, PI3K inhibitors, HDAC inhibitors, and EGFR inhibitors were predicted as four potential mechanisms of drug action (MOA) in high-risk HCC patients. Subsequent analysis has revealed that PBK, CCNA2, and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion, regulating microsatellite instability (MSI), and exerting an impact on HCC progression. CONCLUSIONS: The present study highlights the role of the circRNA-related regulatory network, identifies a four-gene prognostic signature and biomarkers, and further identifies novel therapy for HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , RNA Circular/genética , Prognóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , RNA Endógeno Competitivo , Fosfatidilinositol 3-Quinases , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , MicroRNAs/genética , Microambiente Tumoral , CinesinasRESUMO
Fear extinction allows for adaptive control of learned fear responses but often fails, resulting in a renewal or spontaneous recovery of the extinguished fear, i.e., forgetting of the extinction memory readily occurs. Using an activity-dependent neuronal labeling strategy, we demonstrate that engram neurons for fear extinction memory are dynamically positioned in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and ventral hippocampus (vHPC), which constitute an engram construct in the term of directional engram synaptic connectivity from the BLA or vHPC to mPFC, but not that in the opposite direction, for retrieval of extinction memory. Fear renewal or spontaneous recovery switches the extinction engram construct from an accessible to inaccessible state, whereas additional extinction learning or optogenetic induction of long-term potentiation restores the directional engram connectivity and prevents the return of fear. Thus, the plasticity of engram construct underlies forgetting of extinction memory.
Assuntos
Complexo Nuclear Basolateral da Amígdala , Extinção Psicológica , Extinção Psicológica/fisiologia , Medo/fisiologia , Córtex Pré-Frontal/fisiologia , Condicionamento Psicológico/fisiologia , Complexo Nuclear Basolateral da Amígdala/fisiologiaRESUMO
Cryptorchidism irritant (CI) infection is a major problem in the culturing process of silver pomfret (Pampus argenteus), which can result in rapid and massive death. However, there is limited information available on the immune response of silver pomfret infected by CI. To address this gap, we sampled naturally infected fish and observed milky white translucent oval CI trophozoites on the gills, body surface, and fin rays. Histological analysis showed that CI infection led to vacuolation of epithelial cells and a decrease in blood cells in the gills. We also performed transcriptome profiling of the gill, kidney complex, and spleen, generating 399,616,194 clean reads that assembled into 101,228 unigenes, which were annotated based on public databases. We detected 14,369 differentially expressed genes, and selected several key immune-related genes for further validation using RT-qPCR. The Graft-versus-host pathway and Allograft rejection pathway were enriched in the gills, leading to inflammation and ulceration. CI infection activated the immune system, increasing levels of interleukin-1 beta and MHC class II antigen, and also activated innate and acquired immune genes in silver pomfret. Furthermore, we measured the activities of five immune-related enzymes (SOD, AKP, CAT, CSH and ACP), which all increased to varying degrees after CI infection. Our findings enhance our understanding of the immune response of fish to parasitic infection and may contribute to the development of strategies to prevent high mortality in CI-stimulated fish in aquaculture.
Assuntos
Criptorquidismo , Doenças dos Peixes , Animais , Masculino , Irritantes , Peixes/genética , Perfilação da Expressão Gênica/veterinária , Imunidade , TranscriptomaRESUMO
BACKGROUND: Inflammatory bowel disease (IBS) is a chronic disorder of the gastrointestinal tract. Exosomes have been involved in various pathological processes including IBS. Apigenin has been reported to suppress inflammatory bowel disease (IBS). However, the regulatory roles of exosomes derived from IBS patients (IBS-exos) on human colon epithelial cells are still unclear. METHODS: Exosomes were collected from IBS patients (IBS-exos) and co-cultured with CACO-2 cells. Apigenin was used to treat IBS-exos-treated CACO-2 cells. By exploring the public data bank, we figured out the regulators control the autophagy of CACO-2 cells. RESULTS: Administration of apigenin dose-dependently abolished the inhibitory effect of IBS-exo on the autophagy of CACO-2 cells. A mechanistic study showed that miR-148b-3p bound to 3'UTR to suppress ATG14 and decrease autophagy. Moreover, results suggested that ATG14 overexpression promoted the autophagy of CACO-2 cells in the presence of miR-148b-3p mimic. CONCLUSION: The current study showed that apigenin dose-dependently abolished the inhibitory effect of IBS-exo on CACO-2 cell autophagy by regulating miR-148b-3p/ATG14 signaling.
Assuntos
Apigenina , Exossomos , Síndrome do Intestino Irritável , MicroRNAs , Humanos , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Apigenina/farmacologia , Autofagia , Proteínas Relacionadas à Autofagia/metabolismo , Células CACO-2 , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/patologia , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
Fish cell lines have become a useful tool to study in resource conservation, genetic breeding, diseases control, and environmental pollutants detection. The silver pomfret (Pampus argenteus) is a high-valued marine fish species in aquaculture, which is seriously threatened by various fish diseases. In this study, a new cell line derived from P. argenteus liver (PaL) was established and characterized. PaL cells mainly consisted of fibroblast-like morphology and multiplied well in Leibovitz's L-15 medium supplemented with 15% foetal bovine serum and 3 ng/mL basic fibroblast growth factor at 22°C. Amplification of the Cyt b gene confirmed that the origin of PaL cells as P. argenteus. Chromosome analysis revealed that PaL cells had a diploid Karyotyp. The PaL cells were efficiently transfected with pEGFP-N3 plasmids, indicating its potential application in foreign gene manipulation studies. The PaL cells were found to be susceptible to red sea bream iridovirus (RSIV) and the expression of immune-related gene (TLR5) and apoptosis-related genes (Bax, Cyt c3, CASP9) were upregulated. Furthermore, lipopolysaccharide and palmitic acid (PA) treatments decreased cell viability and up-regulated the expression of inflammation related genes (IL-8, IL-1ß). Meanwhile, PA incubation induced cell apoptosis by Bcl-2-regulated caspase activation. In conclusion, the newly established PaL cell line will be an appropriate in vitro tool for viral propagation and immune response.
Assuntos
Doenças dos Peixes , Perciformes , Animais , Peixes , Perciformes/genética , Fígado , Linhagem CelularRESUMO
Lycium barbarum polysaccharide (LBP) is one of the main active ingredients in the fruit of L. barbarum L. It has been used as herbal medicine for thousands of years in China. In this study, Nile tilapia (Oreochromis niloticus) was taken as the research object. After feeding tilapia with 5 different doses of LBP (0 mg/kg, 500 mg/kg, 1000 mg/kg, 1500 mg/kg, 2000 mg/kg) for 55 d, it was found that LBP could promote the growth of tilapia, and this effect was the strongest at Group 1500 mg/kg. Apoptosis analysis in the liver and spleen showed that dietary supplementation with 1000 mg/kg LBP had the best protective effect on the spleen and liver in tilapia. Combined transcriptomics and metabolomics of the spleen in tilapia at Group 0 mg/kg and 1000 mg/kg showed that the differentially expressed genes (DEGs) such as NT5C2L1, pmm1, FasL and the differentially metabolites such as xanthine, dGMP, guanine and glutamate were mainly concentrated in signaling pathways such as Purine metabolism and FoxO signaling pathway. In conclusion, LBP regulates the metabolic waste levels of tilapia mainly through Purine metabolism and the FoxO signaling pathway, thereby inhibiting cell apoptosis, improving the utilization of nutrients, and promoting the growth of tilapia. This study not only provides a theoretical basis for the application of LBP in aquatic animals but also provides useful information for the healthy development of the aquaculture.
Assuntos
Ciclídeos , Lycium , Animais , Apoptose , Ciclídeos/genética , Medicamentos de Ervas Chinesas , Lycium/metabolismo , Metabolômica , TranscriptomaRESUMO
BACKGROUND: Ischemic stroke, a common central nervous system disease that seriously threatens human life and health, is characterized by rapid progress and a high disability fatality rate. Ischemic tissue can produce a large amount of vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1 (SDF-1) to promote the mobilization of endothelial progenitor cells (EPCs). SUMMARY: As newly discovered stem cells, EPCs can promote angiogenesis in ischemic tissue, repair the damaged vascular endothelium, and maintain vascular homeostasis. Thus, EPCs have become a new research hotspot in this field. This review focuses on the mechanism of EPCs and the intervention of various novel drugs, including small molecules and biomolecules, which will promote the capture, proliferation, and differentiation of EPCs. Then, we explore the promotion of vascular health and the prospect of its application in the treatment of cerebral ischemic stroke (CIS). KEY MESSAGE: It is clinically significant to study the potential of new drug therapy to target EPCs. More effective cytokines, signal pathways, and other drugs should be explored in the future and their specific mechanisms determined. Research should reveal more biological functions of EPCs and achieve their efficient amplification to improve therapy against CIS stroke.
Assuntos
Células Progenitoras Endoteliais , AVC Isquêmico , Neovascularização Fisiológica , Humanos , Células Progenitoras Endoteliais/efeitos dos fármacos , AVC Isquêmico/tratamento farmacológico , Neovascularização Fisiológica/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Temperature is a major environmental factor influence fish growth, development, metabolism and physiological performance. Silver pomfret (Pampus argenteus) is an economically important fishery species, however, the molecular mechanisms responsive to long-term cold stress are still unclear. Hence, we altered water temperature from 13 °C to 8 °C, a logistic fit curve for the survival rate of P. argenteus under a gradient cold stress were thus achieved, 50% survival rate at a measured temperature of 7 °C-7.5 °C. After stimulation, the gill, liver and muscle tissues were investigated through transcriptome, antioxidant enzymes and histological observation. The results showed that antioxidant enzyme and Na+-k+ ATPase activity in gill tissue was significantly increased, tissue damage and apoptosis were observed in multi-tissues. By high-throughput sequencing, a total of 618,097,404 reads of raw data and 598,855,490 reads of clean data were obtained, containing 12,489 differently expressed genes (DEGs). KEGG pathway enrichment analysis showed that DNA replication, protein digestion and absorption, cardiac muscle contraction, adrenergic signaling in cardiomyocytes, and metabolic pathways were significantly enriched in multi-tissues. Fifteen DEGs were selected for real-time PCR (RT-qPCR) analysis, and the results were consistent with transcriptome profiling. Based on the results, we inferred that P. argenteus survived at low temperatures may be achieved by improving the ability to scavenge oxyradical substance and enhancing cell fluidity. This present study indicated that the effects of long-term cold stress on P. argenteus, which is valuable for breeding cold-tolerant P. argenteus stocks for cultivation.
Assuntos
Antioxidantes/metabolismo , Resposta ao Choque Frio , Perciformes , Transcriptoma , Animais , Temperatura Baixa , Perfilação da Expressão Gênica , Perciformes/genéticaRESUMO
Streptococcus agalactiae is an important pathogenic bacterium causing great economic loss in Nile tilapia (Oreochromis niloticus) culture. Resistant and susceptible groups sharing the same genome showed significantly different resistance to S. agalactiae in the genetically improved farmed tilapia strain of Nile tilapia. The resistance mechanism is unclear. We determined genome-wide DNA methylation profiles in spleen of resistant and susceptible O. niloticus at 5 h postinfection with S. agalactiae using whole-genome bisulfite sequencing. The methylation status was higher in the spleen samples from resistant fish than in the susceptible group. A total of 10,177 differentially methylated regions were identified in the two groups, including 3725 differentially methylated genes (DMGs) (3129 hyper-DMGs and 596 hypo-DMGs). The RNA sequencing showed 2374 differentially expressed genes (DEGs), including 1483 upregulated and 891 downregulated. Integrated analysis showed 337 overlapping DEGs and DMGs and 82 overlapping DEGs and differentially methylated region promoters. By integrating promoter DNA methylation with gene expression, we revealed four immune-related genes (Arnt2, Nhr38, Pcdh10, and Ccdc158) as key factors in epigenetic mechanisms contributing to pathogen resistance. Our study provided systematic methylome maps to explore the epigenetic mechanism and reveal the methylation loci of pathogen resistance and identified methylation-regulated genes that are potentially involved in defense against pathogens.
Assuntos
Ciclídeos/genética , Metilação de DNA/genética , Doenças dos Peixes/genética , RNA/genética , Infecções Estreptocócicas/genética , Streptococcus agalactiae/patogenicidade , Animais , Ciclídeos/microbiologia , Regulação para Baixo/genética , Epigênese Genética/genética , Doenças dos Peixes/microbiologia , Análise de Sequência de RNA/métodos , Infecções Estreptocócicas/microbiologia , Regulação para Cima/genéticaRESUMO
BACKGROUND: The Chinese giant salamander Andrias davidianus is an important amphibian species in China because of its increasing economic value, protection status and special evolutionary position from aquatic to terrestrial animal. Its large genome presents challenges to genetic research. Genetic linkage mapping is an important tool for genome assembly and determination of phenotype-related loci. RESULTS: In this study, we constructed a high-density genetic linkage map using ddRAD sequencing technology to obtain SNP genotyping data of members from an full-sib family which sex had been determined. A total of 10,896 markers were grouped and oriented into 30 linkage groups, representing 30 chromosomes of A. davidianus. The genetic length of LGs ranged from 17.61 cM (LG30) to 280.81 cM (LG1), with a mean inter-locus distance ranging from 0.11(LG3) to 0.48 cM (LG26). The total genetic map length was 2643.10 cM with an average inter-locus distance of 0.24 cM. Three sex-related loci and four sex-related markers were found on LG6 and LG23, respectively. CONCLUSION: We constructed the first High-density genetic linkage map and identified three sex-related loci in the Chinese giant salamander. Current results are expected to be a useful tool for future genomic studies aiming at the marker-assisted breeding of the species.
Assuntos
Locos de Características Quantitativas , Urodelos , Animais , China , Mapeamento Cromossômico , Ligação Genética , Polimorfismo de Nucleotídeo Único , Urodelos/genéticaRESUMO
BACKGROUND: The tilapia aquaculture industry is facing heavy economic losses due to Streptococcus agalactiae (S. agalactiae) infections. While progress has been made in past years, the lack of a high-quality tilapia genome and transcript annotations makes systematic and comprehensive exploration for a non-coding RNA regulatory network associated with the infection process unfeasible, and it stunts further research focused on disease defense and treatment. Herein, single molecular real time sequencing (SMRT-Seq) and RNA-seq data were utilized to generate a high-quality transcript annotation. In addition, Changes in mRNA and non-coding RNA expression were also analyzed during a S. agalactiae infection in tilapia. FINDINGS: In total, 16.79 Gb of clean data were obtained by sequencing on six SMRT cells, with 712,294 inserts (326,645 full-length non-chimeric reads and 354,188 non-full-length reads). A total of 197,952 consensus transcripts were obtained. Additionally, 55,857 transcript sequences were acquired, with 12,297 previously annotated and 43,560 newly identified transcripts. To further examine the immune response in Oreochromis niloticus following a S. agalactiae infection, a total of 470.62 Gb of clean data was generated by sequencing a library containing 18 S. agalactiae infected tilapia samples. Of the identified genes, 9911 were newly exploited, of which 7102 were functional annotated. Furthermore, 7874 mRNAs, 1281 long non-coding RNAs (out of 21,860 long non-coding RNAs), and 61 circular RNAs (out of 1026 circular RNAs) were found to be differentially expressed during infection, with the 1026 circRNAs not previously identified in tilapia. Moreover, k-means clustering and WGCNA analyses revealed that the immune response of tilapia to a S. agalactiae infection can be divided into three stages: cytokines driven rapid immune response, energy metabolism promotion, and the production of lysosomes and phagosomes. During this response, the head kidney and spleen have synergistic effects, while maintaining independent characteristics. Finally, lncRNA-mRNA (trans and cis), lncRNA-miRNA-mRNA, and circRNA-miRNA-mRNA regulatory networks were constructed and revealed that non-coding RNA is involved in the regulation of immune-related genes. CONCLUSIONS: This study generated a greatly-improved transcript annotation for tilapia using long-read PacBio sequencing technology, and revealed the presence of a regulatory network comprised of non-coding RNAs in Nile tilapia infected with S. agalactiae.
Assuntos
Ciclídeos , Doenças dos Peixes/imunologia , RNA Circular/imunologia , RNA Longo não Codificante/imunologia , Infecções Estreptocócicas/veterinária , Animais , Doenças dos Peixes/microbiologia , Redes Reguladoras de Genes , RNA Circular/metabolismo , RNA Longo não Codificante/metabolismo , RNA-Seq/veterinária , Imagem Individual de Molécula/veterinária , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/fisiologiaRESUMO
MicroRNAs (miRNAs) play vital regulatory roles in various biological processes, including in immune responses. Nile tilapia (Oreochromis niloticus) is an important commercial fish species in China. To identify immune-related miRNAs of O. niloticus, 4 libraries from liver during S. agalactiae infection (0â¯h, 5â¯h, 50â¯h, and 7â¯d) were sequenced by high-throughput sequencing technology in tilapia. We obtained 10,703,531, 11,507,163, 11,180,179 and 13,408,414 clean reads per library, respectively. In our results, a total of 482 miRNAs were identified through bioinformatic analysis, including 220 conserved miRNAs and 262 putative novel miRNAs. Moreover, 21 (4.36%), 50 (10.37%), and 46 (9.54%) miRNAs were significantly differentially expressed at 5â¯h, 50â¯h and 7â¯d, respectively. In addition, 6939 target genes regulated by these differentially expressed miRNAs were predicted, and their functional annotations were predicted by Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, which revealed that a majority of differentially expressed miRNAs were involved in apoptotic process, metabolic process, and immune responses. Finally, Real-time quantitative PCR experiments were performed for 7 miRNAs by stem-loop RT-PCR, and a general agreement was confirmed between the sequencing and RT-qPCR data. To our understanding, this is the first report of comprehensive identification of O. niloticus miRNAs being differentially regulated in liver related to S. agalactiae infection. This work provides an opportunity for further understanding of the molecular mechanisms of miRNA regulation in O. niloticus host-pathogen interactions, and genetic resources for molecular assistant selection for disease resistant breeding program.
Assuntos
Ciclídeos/genética , Ciclídeos/imunologia , Doenças dos Peixes/imunologia , MicroRNAs/genética , Transcriptoma/imunologia , Animais , Biologia Computacional , MicroRNAs/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae/fisiologiaRESUMO
In mammals, Galectin-3 has been revealed to be widely expressed in immune cells and played important role in immune reactions. However, Galectin-3 is frequently less reported in teleost. In the present study, a molecular characterization and expression analysis of galectin-3 were conducted in GIFT strain Nile tilapia. The full-length cDNA is 1034 bp with 690 bp of protein coding sequences. The result of qRT-PCR showed that the mRNA of galectin-3 was widely expressed in various tissues (heart, liver, spleen, gill, kidney, brain, intestine, skin, muscle, and ovary), and the higher expression was observed in immune-related tissues (liver and spleen). The time-course expression analysis revealed that galectin-3 was significantly up-regulated in intestine (5â¯h, 50â¯h, and 7â¯d), liver (5â¯h, 50â¯h, and 7â¯d), spleen (5 and 50â¯h), head-kidney (5 and 50â¯h), gill (5â¯h and 7â¯d) after Streptococcus agalactiae challenge, and significantly up-regulated in intestine (18, 24, 36, 72, and 96â¯h), liver (6, 18, 24, 96â¯h, and 6â¯d), spleen (18, 24, 36, 72, and 96â¯h), head-kidney (6, 12, 18, 24, 36, 72, and 96â¯h), and gill (12, 18, 24, and 36â¯h) after Aeromonas hydrophila challenge. Taken together, these data suggest that galectin-3 plays a role in immune responses in Nile tilapia after bacterial challenge.
Assuntos
Ciclídeos , Doenças dos Peixes/microbiologia , Galectina 3/genética , Aeromonas hydrophila/fisiologia , Sequência de Aminoácidos , Animais , DNA Complementar , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Galectina 3/imunologia , Galectina 3/metabolismo , Regulação da Expressão Gênica , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Imunidade Inata/genética , Alinhamento de Sequência , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae/fisiologia , Regulação para CimaRESUMO
A full-length cDNA encoding phosphatidylinositol 3-kinase regulatory subunit gamma b gene in Nile tilapia (Oreochromis niloticus), termed as On-pik3r3b, was identified and characterized in this study. The sequence analysis demonstrated that the full-length cDNA of On-pik3r3b was 2018 bp, containing a 5' untranslated region (UTR) of 171 bp, an open reading frame (ORF) of 1422 bp and a 3' UTR of 425 bp. Its protein sequence displayed a high degree of identity with other fish. Using qPCR, the expression patterns of On-pik3r3b were investigated. In healthy Nile tilapia, the transcripts of On-pik3r3b were detected in all examined tissues, except the skin. Upon the stimulation with Streptococcus agalactiae, the On-pik3r3b expression level in liver, spleen, kidney and gill were significantly increased at 12â¯h after infection. The recombinant On-pik3r3b showed in vitro antibacterial activity, against S. agalactiae and E. coli. Our observation strongly indicates that On-pik3r3b is involved in the innate immune response in Nile tilapia.
Assuntos
Ciclídeos/genética , Ciclídeos/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Fosfatidilinositol 3-Quinase/genética , Fosfatidilinositol 3-Quinase/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Fosfatidilinositol 3-Quinase/química , Filogenia , Alinhamento de Sequência/veterináriaRESUMO
One of the highest priority areas for improvement is the development of effective strategies for decreasing disease mortality levels in aquaculture production, a better understanding of the components of the fish immune system and their functions in the context of pathogen invasion is needed. Tilapia is the most common fish in South China, and Streptococcus agalactiae has become the most serious disease problem for tilapia industry in China. Here, we profiled gene expression differences between tilapia differing in their susceptibility to S. agalactiae both basally (before infection) and at three early timepoints post-infection (5â¯h, 50â¯h, and 7â¯d). Between group comparisons revealed 5756 unique genes differentially expressed greater than 2-fold at one or more timepoints. And the resistant fish showed much more strong ability in pathogen recognition, antigen presentation, immune activation, while the susceptible fish showed fast activation of apoptosis. Taken together, the immune profiles expand our knowledge for molecular mechanisms for disease resistance, as well as provide solid molecular resources for further identification of the candidate markers for disease-resistant selection and evaluation of disease prevention and treatment options for tilapia industry.
Assuntos
Ciclídeos/imunologia , Resistência à Doença/imunologia , Doenças dos Peixes/imunologia , Baço/imunologia , Animais , Ciclídeos/genética , Resistência à Doença/genética , Suscetibilidade a Doenças/imunologia , Infecções Estreptocócicas/imunologia , Streptococcus agalactiae/fisiologiaRESUMO
We have systematically changed the number of atomic layers stacked in 2D SnO nanosheet anodes and studied their sodium ion battery (SIB) performance. The results indicate that as the number of atomic SnO layers in a sheet decreases, both the capacity and cycling stability of the Na ion battery improve. The thinnest SnO nanosheet anodes (two to six SnO monolayers) exhibited the best performance. Specifically, an initial discharge and charge capacity of 1072 and 848 mAh g-1 were observed, respectively, at 0.1 A g-1. In addition, an impressive reversible capacity of 665 mAh g-1 after 100 cycles at 0.1 A g-1 and 452 mAh g-1 after 1000 cycles at a high current density of 1.0 A g-1 was observed, with excellent rate performance. As the average number of atomic layers in the anode sheets increased, the battery performance degraded significantly. For example, for the anode sheets with 10-20 atomic layers, only a reversible capacity of 389 mAh g-1 could be obtained after 100 cycles at 0.1 A g-1. Density functional theory calculations coupled with experimental results were used to elucidate the sodiation mechanism of the SnO nanosheets. This systematic study of monolayer-dependent physical and electrochemical properties of 2D anodes shows a promising pathway to engineering and mitigating volume changes in 2D anode materials for sodium ion batteries. It also demonstrates that ultrathin SnO nanosheets are promising SIB anode materials with high specific capacity, stable cyclability, and excellent rate performance.
RESUMO
Innate immune system is the primary defense mechanism against pathogen infection in teleost, which are living in pathogen-rich aquatic environment. It has been long hypothesized that the disease resistance in teleost are strongly correlated to the activities of innate immune genes. Tilapia is an important economical fish around the world, especially in China, where the production accounts for nearly half of the global production. Recently, S. agalactiae has become one of the most serious bacterial diseases in southern China, resulted in high cumulative mortality and economic loss to tilapia industry. Therefore, we sought here to characterize the expression profiles of tilapia against S. agalactiae infection at whole transcriptome level by RNA-seq technology. A total of 2822 genes were revealed significantly expressed in tilapia spleen with a general trend of induction. Notably, most of the genes were rapidly the most induced at the early timepoint. The significantly changed genes highlighted the function of pathogen attachment and recognition, antioxidant/apoptosis, cytoskeletal rearrangement, and immune activation. Collectively, the induced expression patterns suggested the strong ability of tilapia to rapidly recognize the invasive bacteria, and activation of downstream immune signaling pathways to clear the bacteria and prevent the tissue damage and bacteria triggered cell apoptosis. Our results heighted important roles of novel candidate genes which were often missed in previous tilapia studies. Further studies are needed to characterize the molecular relationships between key immune genes and disease resistance, and to identify the candidate genes for molecular-assistant selection of disease-resistant broodstock and evaluation of disease prevention and treatment measures.
Assuntos
Ciclídeos , Doenças dos Peixes/genética , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae/fisiologia , Transcriptoma , Animais , Doenças dos Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Infecções Estreptocócicas/genética , Infecções Estreptocócicas/imunologiaRESUMO
Functional gastrointestinal disorders (FGIDs) are manifested as digestive symptoms, but relative symptoms cannot be confirmed by traditional inspection methods. In 2015 Rome Foundation put forward the conception of multi-dimensional clinical profile (MDCP) for FGIDs, which emphasized multi-dimensional assessment of disease state and aimed to develop individualized treatment program. Chinese medicine also has multi-dimensional thoughts in diagnosis and treatment and has much in com- mon with MDCP in refining diagnosis, attaching importance to psychological factors and spirits, seeking biomarkers, and so on. The correlation between multi-dimensional diagnostic and therapeutic thoughts in Chinese medicine and MDCP was explored by combining functional dyspepsia as focal point.
Assuntos
Gastroenteropatias , Medicina Tradicional Chinesa , Doenças do Sistema Digestório , Dispepsia/diagnóstico , Dispepsia/terapia , Gastrite , Gastroenteropatias/diagnóstico , Gastroenteropatias/terapia , Humanos , Medicina Tradicional do Leste AsiáticoRESUMO
Streptococcus iniae is the most significant bacterial disease of tilapia throughout the world, and commonly leads to tremendous economic losses. In contrast to other important fish species, our knowledge about the molecular mechanisms of tilapia in response to bacterial infection is still limited. Here, therefore, we utilized RNA-seq to first profiling of host responses in tilapia spleen following S. iniae infection at transcriptome level. A total of 223 million reads were obtained and assembled into 192,884 contigs with average length 844 bp. Gene expression analysis between control and infected samples at 5 h, 50 h, and 7 d revealed 1475 differentially expressed genes. In particular, the differentially expressed gene set was dramatically induced as early as 5 h, and rapidly declined to basal levels at 50 h. Enrichment and pathway analysis of the differentially expressed genes revealed the centrality of the pathogen attachment and recognition, cytoskeletal rearrangement and immune activation/inflammation in the pathogen entry and host inflammatory responses. Understanding of these responses can highlight mechanisms of tilapia host defense, and expand our knowledge of teleost immunology. Our findings will set a foundation of valuable biomarkers for future individual, strain, and family-level studies to evaluate immune effect of vaccine and individual response in host defense mechanisms to S. iniae infection, to select disease resistant families and strains.
Assuntos
Ciclídeos/genética , Ciclídeos/imunologia , Doenças dos Peixes , Infecções Estreptocócicas , Streptococcus , Animais , Doenças dos Peixes/genética , Doenças dos Peixes/imunologia , Perfilação da Expressão Gênica , Análise de Sequência de RNA , Baço/imunologia , Infecções Estreptocócicas/genética , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/veterinária , TranscriptomaRESUMO
BACKGROUND: The pathogenesis of biliary atresia (BA) remains elusive. We aimed to investigate the role of long noncoding RNA (lncRNA) MEG9 in BA. METHODS: LncRNA microarray was conducted to identify differentially expressed lncRNAs in three BA and three para-hepatoblastoma liver tissues. RT-qPCR validated the results. Human intrahepatic bile duct epithelial cells (HIBECs) were stably transfected with lncRNA MEG9 knockdown/overexpression to investigate its cellular localization and function. RNA sequencing (RNA-seq), differentially expressed genes (DEGs) analysis and gene set enrichment analysis were applied to MEG9-overexpresed HIBECs. RNA pull-down and mass spectrometry explored the interacting protein of MEG9, while clinical information was reviewed. RESULTS: 436 differentially expressed lncRNAs were identified, with MEG9 highly upregulated in BA. RT-qPCR further confirmed MEG9's overexpression in BA and diagnostic potential (AUC = 0.9691). MEG9 was predominantly located in the nucleus and significantly promoted cell proliferation and migration. RNA-seq revealed inflammation- and extracellular matrix-related pathways enriched in MEG9-overexpressing HIBECs, with upregulated cytokine genes like CXCL6 and IL6. MMP-7 and collagen I were also overexpressed. Furthermore, 38 proteins were identified to specifically interact with MEG9, and S100A9 was highly expressed in cell models. S100A9 was also significantly upregulated in BA liver tissue and correlated with MEG9 expression (r = 0.313, p < 0.05), albumin level (r = -0.349, p < 0.05), and platelet level (r = -0.324, p < 0.05). CONCLUSION: MEG9 influences cholangiocyte proliferation, migration, and cytokine production, potentially regulating BA inflammation and fibrosis via S100A9 interaction.