Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 42.753
Filtrar
1.
Sci Total Environ ; 783: 147130, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34088150

RESUMO

The effects of global warming and anthropogenic disturbance force animals to migrate from lower to higher elevations to find suitable new habitats. As such migrations increase hypoxic stress on the animals, it is important to understand how plateau- and plain-dwelling animals respond to low-oxygen environments. We used comparative transcriptomics to explore the response of Neodon fuscus, Lasiopodomys brandtii, and Mus musculus skeletal muscle tissues to hypoxic conditions. Results indicate that these species have adopted different oxygen transport and energy metabolism strategies for dealing with a hypoxic environment. N. fuscus promotes oxygen transport by increasing hemoglobin synthesis and reduces the risk of thrombosis through cooperative regulation of genes, including Fga, Fgb, Alb, and Ttr; genes such as Acs16, Gpat4, and Ndufb7 are involved in regulating lipid synthesis, fatty acid ß-oxidation, hemoglobin synthesis, and electron-linked transmission, thereby maintaining a normal energy supply in hypoxic conditions. In contrast, the oxygen-carrying capacity and angiogenesis of red blood cells in L. brandtii are promoted by genes in the CYP and COL families; this species maintains its bodily energy supply by enhancing the pentose phosphate pathway and mitochondrial fatty acid synthesis pathway. However, under hypoxia, M. musculus cannot effectively transport additional oxygen; thus, its cell cycle, proliferation, and migration are somewhat affected. Given its lack of hypoxic tolerance experience, M. musculus also shows significantly reduced oxidative phosphorylation levels under hypoxic conditions. Our results suggest that the glucose capacity of M. musculus skeletal muscle does not provide sufficient energy during hypoxia; thus, we hypothesize that it supplements its bodily energy by synthesizing ketone bodies. For the first time, we describe the energy metabolism pathways of N. fuscus and L. brandtii skeletal muscle tissues under hypoxic conditions. Our findings, therefore, improve our understanding of how vertebrates thrive in high altitude and plain habitats when faced with hypoxic conditions.


Assuntos
Hipóxia , Transcriptoma , Animais , Arvicolinae/genética , Metabolismo Energético , Feminino , Camundongos , Músculo Esquelético/metabolismo
2.
BMC Genomics ; 22(1): 416, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090338

RESUMO

BACKGROUND: Copper was used for many years in aquaculture operations as an effective algaecide or a parasite treatment of fish. It is an essential nutrient with numerous functions in organisms, but is toxic at high concentrations. However, the toxicity of copper to fish remains unclear. In this study, we used the piebald naked carp, Gymnocypris eckloni, as a model. RNA-seq data from different tissues, including gills, kidney, and liver, were used to investigate the underlying mechanism of copper toxicology in G. eckloni. RESULTS: We compared the transcriptomes from different tissues with different time durations of copper ion treatment. After 72 h copper ion treatment, the number of genes with different expression in gills and liver changed dramatically, but not in kidneys. In KEGG functional enrichment, the pattern of differentially expressed genes (DEGs) was also similar in the gills and liver. The most enriched pathway of DEGs was "Ribosome" in both tissues. Furthermore, we analyzed the expression levels of genes involved in oxidative stress response and protein synthesis using qPCR and RNA-seq data. Our results showed that several genes involved in oxidative stress response were up-regulated both in gills and liver. Up-regulation of these genes indicated that copper treatment caused oxidative stress, which is likely to result in ribosome damage. In addition, our results showed that the expression of Eef1b2, a transcription elongation factor, was decreased in the liver under oxidative stress, and the expression of translation initiation factors Eif4ebp1 and eIF2α, and elongation factor eEF2 was up-regulated. These results supported the idea that oxidative stress inhibits protein synthesis in cells. CONCLUSIONS: Our results indicate that copper exposure caused different responses in different tissues, since the gene expression patterns changed substantially either in the gills or liver, while the effect on the kidney was relatively weak. Furthermore, our results indicated that the expression pattern of the genes involved in the ribosome, which is a complex molecular machine orchestrating protein synthesis in the cell, together with translation initiation factor and elongation factors, were affected by copper exposure both in the gills and liver of piebald naked carp. This result leads us to speculate that the downregulation of global protein synthesis is an acute response strategy of fish to metal-induced oxidative stress. Moreover, we speculate that this strategy not only exists in the selective translation of proteins but also exists in the specific translation of functional proteins in tissues and cells.


Assuntos
Carpas , Animais , Carpas/genética , Cobre/toxicidade , Perfilação da Expressão Gênica , Brânquias , Transcriptoma
3.
BMC Plant Biol ; 21(1): 249, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059002

RESUMO

BACKGROUND: Walnut anthracnose induced by Colletotrichum gloeosporioides is a disastrous disease affecting walnut production. The resistance of walnut fruit to C. gloeosporioides is a highly complicated and genetically programmed process. However, the underlying mechanisms have not yet been elucidated. RESULTS: To understand the molecular mechanism underlying the defense of walnut to C. gloeosporioides, we used RNA sequencing and label-free quantitation technologies to generate transcriptomic and proteomic profiles of tissues at various lifestyle transitions of C. gloeosporioides, including 0 hpi, pathological tissues at 24 hpi, 48 hpi, and 72 hpi, and distal uninoculated tissues at 120 hpi, in anthracnose-resistant F26 fruit bracts and anthracnose-susceptible F423 fruit bracts, which were defined through scanning electron microscopy. A total of 21,798 differentially expressed genes (DEGs) and 1929 differentially expressed proteins (DEPs) were identified in F26 vs. F423 at five time points, and the numbers of DEGs and DEPs were significantly higher in the early infection stage. Using pairwise comparisons and weighted gene co-expression network analysis of the transcriptome, we identified two modules significantly related to disease resistance and nine hub genes in the transcription expression gene networks. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the DEGs and DEPs revealed that many genes were mainly related to immune response, plant hormone signal transduction, and secondary metabolites, and many DEPs were involved in carbon metabolism and photosynthesis. Correlation analysis between the transcriptome data and proteome data also showed that the consistency of the differential expression of the mRNA and corresponding proteins was relatively higher in the early stage of infection. CONCLUSIONS: Collectively, these results help elucidate the molecular response of walnut fruit to C. gloeosporioides and provide a basis for the genetic improvement of walnut disease resistance.


Assuntos
Colletotrichum , Juglans/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Frutas/genética , Frutas/microbiologia , Juglans/genética , Proteoma , Transcriptoma
4.
BMC Bioinformatics ; 22(1): 301, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34088262

RESUMO

BACKGROUND: Network models are well-established as very useful computational-statistical tools in cell biology. However, a genomic network model based only on gene expression data can, by definition, only infer gene co-expression networks. Hence, in order to infer gene regulatory patterns, it is necessary to also include data related to binding of regulatory factors to DNA. RESULTS: We propose a new dynamic genomic network model, for inferring patterns of genomic regulatory influence in dynamic processes such as development. Our model fuses experiment-specific gene expression data with publicly available DNA-binding data. The method we propose is computationally efficient, and can be applied to genome-wide data with tens of thousands of transcripts. Thus, our method is well suited for use as an exploratory tool for genome-wide data. We apply our method to data from human fetal cortical development, and our findings confirm genomic regulatory patterns which are recognised as being fundamental to neuronal development. CONCLUSIONS: Our method provides a mathematical/computational toolbox which, when coupled with targeted experiments, will reveal and confirm important new functional genomic regulatory processes in mammalian development.


Assuntos
Genômica , Transcriptoma , Animais , Biologia Computacional , Redes Reguladoras de Genes , Genoma , Humanos
5.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068366

RESUMO

Magnaporthe oryzae (M. oryzae) is a typical cause of rice blast in agricultural production. Isobavachalcone (IBC), an active ingredient of Psoralea corylifolia L. extract, is an effective fungicide against rice blast. To determine the mechanism of IBC against M. oryzae, the effect of IBC on the metabolic pathway of M. oryzae was explored by transcriptome profiling. In M. oryzae, the expression of pyruvate dehydrogenase E1 (PDHE1), part of the tricarboxylic acid (TCA cycle), was significantly decreased in response to treatment with IBC, which was verified by qPCR and testing of enzyme activity. To further elucidate the interactions between IBC and PDHE1, the 3D structure model of the PDHE1 from M. oryzae was established based on homology modeling. The model was utilized to analyze the molecular interactions through molecular docking and molecular dynamics simulation, revealing that IBC has π-π stacking interactions with residue TYR139 and undergoes hydrogen bonding with residue ASP217 of PDHE1. Additionally, the nonpolar residues PHE111, MET174, ILE 187, VAL188, and MET250 form strong hydrophobic interactions with IBC. The above results reveal that PDHE1 is a potential target for antifungal agents, which will be of great significance for guiding the design of new fungicides. This research clarified the mechanism of IBC against M. oryzae at the molecular level, which will underpin further studies of the inhibitory mechanism of flavonoids and the discovery of new targets. It also provides theoretical guidance for the field application of IBC.


Assuntos
Chalconas/farmacologia , Proteínas Fúngicas/metabolismo , Magnaporthe/efeitos dos fármacos , Oryza/enzimologia , Doenças das Plantas/imunologia , Piruvato Desidrogenase (Lipoamida)/antagonistas & inibidores , Transcriptoma/efeitos dos fármacos , Proteínas Fúngicas/genética , Fungicidas Industriais/farmacologia , Perfilação da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Magnaporthe/fisiologia , Simulação de Acoplamento Molecular , Oryza/efeitos dos fármacos , Oryza/microbiologia , Doenças das Plantas/microbiologia , Conformação Proteica , Piruvato Desidrogenase (Lipoamida)/genética , Piruvato Desidrogenase (Lipoamida)/metabolismo
6.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068395

RESUMO

As a crucial step for human reproduction, embryo implantation is a low-efficiency process. Despite rapid advances in recent years, the molecular mechanism underlying embryo implantation remains poorly understood. Here, we used the mouse as an animal model and generated a single-cell transcriptomic atlas of embryo implantation sites. By analyzing inter-implantation sites of the uterus as control, we were able to identify global gene expression changes associated with embryo implantation in each cell type. Additionally, we predicted signaling interactions between uterine luminal epithelial cells and mural trophectoderm of blastocysts, which represent the key mechanism of embryo implantation. We also predicted signaling interactions between uterine epithelial-stromal crosstalk at implantation sites, which are crucial for post-implantation development. Our data provide a valuable resource for deciphering the molecular mechanism underlying embryo implantation.


Assuntos
Blastocisto/fisiologia , Comunicação Celular , Implantação do Embrião , Desenvolvimento Embrionário , Análise de Célula Única/métodos , Transcriptoma , Útero/fisiologia , Animais , Blastocisto/citologia , Feminino , Masculino , Camundongos , Transdução de Sinais , Útero/citologia
7.
World J Gastroenterol ; 27(21): 2850-2870, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34135558

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19), a pandemic contributing to more than 105 million cases and more than 2.3 million deaths worldwide, was described to be frequently accompanied by extrapulmonary manifestations, including liver dysfunction. Liver dysfunction and elevated liver enzymes were observed in about 53% of COVID-19 patients. AIM: To gain insight into transcriptional abnormalities in liver tissue of severe COVID-19 patients that may result in liver dysfunction. METHODS: The transcriptome of liver autopsy samples from severe COVID-19 patients against those of non-COVID donors was analyzed. Differentially expressed genes were identified from normalized RNA-seq data and analyzed for the enrichment of functional clusters and pathways. The differentially expressed genes were then compared against the genetic signatures of liver diseases including cirrhosis, fibrosis, non-alcoholic fatty liver disease (NAFLD), and hepatitis A/B/C. Gene expression of some differentially expressed genes was assessed in the blood samples of severe COVID-19 patients with liver dysfunction using qRT-PCR. RESULTS: Analysis of the differential transcriptome of the liver tissue of severe COVID-19 patients revealed a significant upregulation of transcripts implicated in tissue remodeling including G-coupled protein receptors family genes, DNAJB1, IGF2, EGFR, and HDGF. Concordantly, the differential transcriptome of severe COVID-19 liver tissues substantially overlapped with the disease signature of liver diseases characterized with pathological tissue remodeling (liver cirrhosis, Fibrosis, NAFLD, and hepatitis A/B/C). Moreover, we observed a significant suppression of transcripts implicated in metabolic pathways as well as mitochondrial function, including cytochrome P450 family members, ACAD11, CIDEB, GNMT, and GPAM. Consequently, drug and xenobiotics metabolism pathways are significantly suppressed suggesting a decrease in liver detoxification capacity. In correspondence with the RNA-seq data analysis, we observed a significant upregulation of DNAJB1 and HSP90AB1 as well as significant downregulation of CYP39A1 in the blood plasma of severe COVID-19 patients with liver dysfunction. CONCLUSION: Severe COVID-19 patients appear to experience significant transcriptional shift that may ensue tissue remodeling, mitochondrial dysfunction and lower hepatic detoxification resulting in the clinically observed liver dysfunction.


Assuntos
COVID-19 , Hepatopatia Gordurosa não Alcoólica , Proteínas de Choque Térmico HSP40 , Humanos , Fígado , SARS-CoV-2 , Esteroide Hidroxilases , Biologia de Sistemas , Transcriptoma
8.
J Int Med Res ; 49(6): 3000605211021043, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34111996

RESUMO

OBJECTIVE: Uterine carcinosarcoma (UCS) is a rare, aggressive tumour with a high metastasis rate and poor prognosis. This study aimed to explore potential key genes associated with the prognosis of UCS. METHODS: Transcriptional expression data were downloaded from the Gene Expression Profiling Interactive Analysis database and differentially expressed genes (DEGs) were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses using Metascape. A protein-protein interaction network was constructed using the STRING website and Cytoscape software, and the top 30 genes obtained through the Maximal Clique Centrality algorithm were selected as hub genes. These hub genes were validated by clinicopathological and sequencing data for 56 patients with UCS from The Cancer Genome Atlas database. RESULTS: A total of 1894 DEGs were identified, and the top 30 genes were considered as hub genes. Hyaluronan-mediated motility receptor (HMMR) expression was significantly higher in UCS tissues compared with normal tissues, and elevated expression of HMMR was identified as an independent prognostic factor for shorter survival in patients with UCS. CONCLUSIONS: These results suggest that HMMR may be a potential biomarker for predicting the prognosis of patients with UCS.


Assuntos
Carcinossarcoma , Biologia Computacional , Proteínas da Matriz Extracelular/genética , Receptores de Hialuronatos/genética , Biomarcadores Tumorais/genética , Carcinossarcoma/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Transcriptoma
9.
BMC Genomics ; 22(1): 438, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34112090

RESUMO

BACKGROUND: Myofibrillar myopathy in humans causes protein aggregation, degeneration, and weakness of skeletal muscle. In horses, myofibrillar myopathy is a late-onset disease of unknown origin characterized by poor performance, atrophy, myofibrillar disarray, and desmin aggregation in skeletal muscle. This study evaluated molecular and ultrastructural signatures of myofibrillar myopathy in Warmblood horses through gluteal muscle tandem-mass-tag quantitative proteomics (5 affected, 4 control), mRNA-sequencing (8 affected, 8 control), amalgamated gene ontology analyses, and immunofluorescent and electron microscopy. RESULTS: We identified 93/1533 proteins and 47/27,690 genes that were significantly differentially expressed. The top significantly differentially expressed protein CSRP3 and three other differentially expressed proteins, including, PDLIM3, SYNPO2, and SYNPOL2, are integrally involved in Z-disc signaling, gene transcription and subsequently sarcomere integrity. Through immunofluorescent staining, both desmin aggregates and CSRP3 were localized to type 2A fibers. The highest differentially expressed gene CHAC1, whose protein product degrades glutathione, is associated with oxidative stress and apoptosis. Amalgamated transcriptomic and proteomic gene ontology analyses identified 3 enriched cellular locations; the sarcomere (Z-disc & I-band), mitochondrial complex I and the extracellular matrix which corresponded to ultrastructural Z-disc disruption and mitochondrial cristae alterations found with electron microscopy. CONCLUSIONS: A combined proteomic and transcriptomic analysis highlighted three enriched cellular locations that correspond with MFM ultrastructural pathology in Warmblood horses. Aberrant Z-disc mechano-signaling, impaired Z-disc stability, decreased mitochondrial complex I expression, and a pro-oxidative cellular environment are hypothesized to contribute to the development of myofibrillar myopathy in Warmblood horses. These molecular signatures may provide further insight into diagnostic biomarkers, treatments, and the underlying pathophysiology of MFM.


Assuntos
Proteômica , Sarcômeros , Animais , Matriz Extracelular/genética , Cavalos , Músculo Esquelético , Miopatias Congênitas Estruturais , Transcriptoma
10.
BMC Genomics ; 22(1): 437, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34112105

RESUMO

BACKGROUND: Biomineralization by molluscs involves regulated deposition of calcium carbonate crystals within a protein framework to produce complex biocomposite structures. Effective biomineralization is a key trait for aquaculture, and animal resilience under future climate change. While many enzymes and structural proteins have been identified from the shell and in mantle tissue, understanding biomieralization is impeded by a lack of fundamental knowledge of the genes and pathways involved. In adult bivalves, shells are secreted by the mantle tissue during growth, maintenance and repair, with the repair process, in particular, amenable to experimental dissection at the transcriptomic level in individual animals. RESULTS: Gene expression dynamics were explored in the adult blue mussel, Mytilus edulis, during experimentally induced shell repair, using the two valves of each animal as a matched treatment-control pair. Gene expression was assessed using high-resolution RNA-Seq against a de novo assembled database of functionally annotated transcripts. A large number of differentially expressed transcripts were identified in the repair process. Analysis focused on genes encoding proteins and domains identified in shell biology, using a new database of proteins and domains previously implicated in biomineralization in mussels and other molluscs. The genes implicated in repair included many otherwise novel transcripts that encoded proteins with domains found in other shell matrix proteins, as well as genes previously associated with primary shell formation in larvae. Genes with roles in intracellular signalling and maintenance of membrane resting potential were among the loci implicated in the repair process. While haemocytes have been proposed to be actively involved in repair, no evidence was found for this in the M. edulis data. CONCLUSIONS: The shell repair experimental model and a newly developed shell protein domain database efficiently identified transcripts involved in M. edulis shell production. In particular, the matched pair analysis allowed factoring out of much of the inherent high level of variability between individual mussels. This snapshot of the damage repair process identified a large number of genes putatively involved in biomineralization from initial signalling, through calcium mobilization to shell construction, providing many novel transcripts for future in-depth functional analyses.


Assuntos
Mytilus edulis , Exoesqueleto , Animais , Biomineralização , Perfilação da Expressão Gênica , Mytilus edulis/genética , Transcriptoma
11.
BMC Bioinformatics ; 22(1): 318, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34116627

RESUMO

BACKGROUND: Drug-drug interaction (DDI) is a serious public health issue. The L1000 database of the LINCS project has collected millions of genome-wide expressions induced by 20,000 small molecular compounds on 72 cell lines. Whether this unified and comprehensive transcriptome data resource can be used to build a better DDI prediction model is still unclear. Therefore, we developed and validated a novel deep learning model for predicting DDI using 89,970 known DDIs extracted from the DrugBank database (version 5.1.4). RESULTS: The proposed model consists of a graph convolutional autoencoder network (GCAN) for embedding drug-induced transcriptome data from the L1000 database of the LINCS project; and a long short-term memory (LSTM) for DDI prediction. Comparative evaluation of various machine learning methods demonstrated the superior performance of our proposed model for DDI prediction. Many of our predicted DDIs were revealed in the latest DrugBank database (version 5.1.7). In the case study, we predicted drugs interacting with sulfonylureas to cause hypoglycemia and drugs interacting with metformin to cause lactic acidosis, and showed both to induce effects on the proteins involved in the metabolic mechanism in vivo. CONCLUSIONS: The proposed deep learning model can accelerate the discovery of new DDIs. It can support future clinical research for safer and more effective drug co-prescription.


Assuntos
Aprendizado Profundo , Diabetes Mellitus , Preparações Farmacêuticas , Análise de Dados , Interações Medicamentosas , Humanos , Transcriptoma
12.
BMC Genomics ; 22(1): 441, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118873

RESUMO

BACKGROUND: Lower selection intensities in indigenous breeds of Chinese pig have resulted in obvious genetic and phenotypic divergence. One such breed, the Nanyang black pig, is renowned for its high lipid deposition and high genetic divergence, making it an ideal model in which to investigate lipid position trait mechanisms in pigs. An understanding of lipid deposition in pigs might improve pig meat traits in future breeding and promote the selection progress of pigs through modern molecular breeding techniques. Here, transcriptome and tandem mass tag-based quantitative proteome (TMT)-based proteome analyses were carried out using longissimus dorsi (LD) tissues from individual Nanyang black pigs that showed high levels of genetic variation. RESULTS: A large population of Nanyang black pigs was phenotyped using multi-production trait indexes, and six pigs were selected and divided into relatively high and low lipid deposition groups. The combined transcriptomic and proteomic data identified 15 candidate genes that determine lipid deposition genetic divergence. Among them, FASN, CAT, and SLC25A20 were the main causal candidate genes. The other genes could be divided into lipid deposition-related genes (BDH2, FASN, CAT, DHCR24, ACACA, GK, SQLE, ACSL4, and SCD), PPARA-centered fat metabolism regulatory factors (PPARA, UCP3), transcription or translation regulators (SLC25A20, PDK4, CEBPA), as well as integrin, structural proteins, and signal transduction-related genes (EGFR). CONCLUSIONS: This multi-omics data set has provided a valuable resource for future analysis of lipid deposition traits, which might improve pig meat traits in future breeding and promote the selection progress in pigs, especially in Nanyang black pigs.


Assuntos
Proteômica , Transcriptoma , Animais , Biologia Computacional , Metabolismo dos Lipídeos/genética , Fenótipo , Suínos/genética
13.
Commun Biol ; 4(1): 654, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34079039

RESUMO

SARS-CoV-2 infection of human airway epithelium activates genetic programs leading to progressive hyperinflammation in COVID-19 patients. Here, we report on transcriptomes activated in primary airway cells by interferons and their suppression by Janus kinase (JAK) inhibitors. Deciphering the regulation of the angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2, is paramount for understanding the cell tropism of SARS-CoV-2 infection. ChIP-seq for activating histone marks and Pol II loading identified candidate enhancer elements controlling the ACE2 locus, including the intronic dACE2 promoter. Employing RNA-seq, we demonstrate that interferons activate expression of dACE2 and, to a lesser extent, the genuine ACE2 gene. Interferon-induced gene expression was mitigated by the JAK inhibitors baricitinib and ruxolitinib, used therapeutically in COVID-19 patients. Through integrating RNA-seq and ChIP-seq data we provide an in-depth understanding of genetic programs activated by interferons, and our study highlights JAK inhibitors as suitable tools to suppress these in bronchial cells.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , Antivirais/farmacologia , COVID-19/tratamento farmacológico , Interferons/farmacologia , Inibidores de Janus Quinases/farmacologia , Ativação Transcricional/efeitos dos fármacos , COVID-19/genética , Linhagem Celular , Humanos , Mucosa Respiratória/citologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia , Transcriptoma/efeitos dos fármacos
14.
BMC Gastroenterol ; 21(1): 262, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118888

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) can lead to liver failure which renders to liver transplant. miRNAs might be detected as biomarkers in subclinical stage of several hepatobiliary disorders like HCC. Therefore, in the present study, alterations in miRNAs as biomarkers were detected in LT patients with HCC. METHODS: Fourteen tissue samples composed of 5 rejected and 9 non-rejected ones were used for studying the miRNAs expression pattern using LNA-array probe assay and the result was evaluated by in house SYBR Green Real-time PCR protocols on 30 other tissue samples composed of 10 rejected and 20 non-rejected ones for the selected miRNAs. All samples were collected from liver transplanted patients with HCC. RESULTS: The study results revealed that in rejected patients compared to non-rejected ones, hsa-miR-3158-5p, -4449, -4511, and -4633-5p were up-regulated and hsa-miR-122-3p, -194-5p, 548as-3p, and -4284 were down-regulated. ROC curve analysis also confirmed that miR194-5p and -548as-3p in up-regulated and also, miR-3158-5p, -4449 in down-regulated microRNAs are significantly important molecules in rejection. CONCLUSION: Finally, the tissue levels of specific miRNAs (especially hsa-miR-3158-5p, -4449, -194-5p and -548as-3p) significantly correlated with the development of HCC, which can be present as biomarkers after further completing studies.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , MicroRNAs , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/cirurgia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgia , MicroRNAs/genética , Transcriptoma
15.
Int J Mol Sci ; 22(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071656

RESUMO

The olive tree (Olea europaea L. subsp. europaea) is the most important perennial crop in the Mediterranean region, producing table olives and oil, both appreciated for their nutraceutical value. Although olive oil quality traits have been extensively studied, much less attention has been paid to olive drupe. Olive drupe ripening is an extremely complex process involving numerous physiological and molecular changes that are unique in this fruit crop species. This review underlines the contribution of "-omics" techniques and of the recent advances in bioinformatics and analytical tools, notably next-generation sequencing and mass spectrometry, for the characterization of the olive ripening syndrome. The usage of high-dimensional datasets, such as transcriptomics, proteomics, and metabolomics, will provide a systematical description of the molecular-specific processes regulating olive fruit development and ripening. However, the incomplete sequence of the O. europaea L. reference genome has largely hampered the utilization of omics tools towards olive drupe research. Due to this disadvantage, the most reported -omics studies on fruit trees concern metabolomics and only a few transcriptomics and proteomics. In this review, up-to-date applications of -omics technologies towards olive drupe biology are addressed, and future perspectives in olive fruit research are highlighted.


Assuntos
Frutas/metabolismo , Genômica , Metabolômica , Olea , Biologia Computacional , Frutas/química , Genoma de Planta , Sequenciamento de Nucleotídeos em Larga Escala , Olea/química , Olea/genética , Olea/metabolismo , Proteoma , Proteômica , Transcriptoma
16.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072468

RESUMO

Senescence, sterile inflammation, and infection cause dysfunction of corneal endothelial cells, leading to visual morbidity that may require corneal transplantation. With increasing age, the extracellular matrix is modified by non-enzymatic glycation forming advanced glycation end products (AGEs). The modifications are primarily sensed by the receptors for the AGEs (RAGE) and are manifested as a type I interferon response. Interestingly, in our study, human corneal endothelial cells (HCEn) cells did not respond to the typical RAGE ligands, including the AGEs, high mobility group box 1 (HMGB1), and serum amyloid-A (SAA). Instead, HCEn cells responded exclusively to the CpG DNA, which is possessed by typical corneal pathogen, herpes simplex virus-1 (HSV-1). Upon HSV-1 infection, the surface expression of RAGE was increased, and endocytosed HSV-1 was associated with RAGE and CpG DNA receptor, TLR9. RAGE DNA transfection markedly increased interferon-ß secretion by CpG DNA or HSV-1 infection. HSV-1 infection-induced interferon-ß secretion was abolished by TLR9 inhibition and partially by RAGE inhibition. Global transcriptional response analysis confirmed that RAGE and TLR9 were both significantly involved in type I interferon responses. We conclude that RAGE is a sensor of HSV-1 infection and provokes a type I interferon response.


Assuntos
Epitélio Posterior/metabolismo , Epitélio Posterior/virologia , Herpesvirus Humano 1 , Ceratite Herpética/metabolismo , Ceratite Herpética/virologia , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Biomarcadores , Células Cultivadas , Biologia Computacional/métodos , Ilhas de CpG , Metilação de DNA , Suscetibilidade a Doenças , Células Endoteliais/metabolismo , Células Endoteliais/virologia , Epitélio Posterior/patologia , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Receptor para Produtos Finais de Glicação Avançada/genética , Transcriptoma
17.
Mem Inst Oswaldo Cruz ; 116: e200547, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076041

RESUMO

BACKGROUND: Forty percent of the world's population live in areas where they are at risk from dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Dengue viruses are transmitted primarily by the mosquito Aedes aegypti. In Cali, Colombia, approximately 30% of field collected Ae. aegypti are naturally refractory to all four dengue serotypes. OBJECTIVES: Use RNA-sequencing to identify those genes that determine refractoriness in feral mosquitoes to dengue. This information can be used in gene editing strategies to reduce dengue transmission. METHODS: We employed a full factorial design, analyzing differential gene expression across time (24, 36 and 48 h post bloodmeal), feeding treatment (blood or blood + dengue-2) and strain (susceptible or refractory). Sequences were aligned to the reference Ae. aegypti genome for identification, assembled to visualize transcript structure, and analyzed for dynamic gene expression changes. A variety of clustering techniques was used to identify the differentially expressed genes. FINDINGS: We identified a subset of genes that likely assist dengue entry and replication in susceptible mosquitoes and contribute to vector competence. MAIN CONCLUSIONS: The differential expression of specific genes by refractory and susceptible mosquitoes could determine the phenotype, and may be used to in gene editing strategies to reduce dengue transmission.


Assuntos
Aedes , Vírus da Dengue , Dengue , Aedes/genética , Animais , Colômbia , Vírus da Dengue/genética , Mosquitos Vetores/genética , RNA , Transcriptoma/genética
18.
Science ; 372(6546): 1068-1073, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34083484

RESUMO

Mammalian medial and lateral hippocampal networks preferentially process spatial- and object-related information, respectively. However, the mechanisms underlying the assembly of such parallel networks during development remain largely unknown. Our study shows that, in mice, complementary expression of cell surface molecules teneurin-3 (Ten3) and latrophilin-2 (Lphn2) in the medial and lateral hippocampal networks, respectively, guides the precise assembly of CA1-to-subiculum connections in both networks. In the medial network, Ten3-expressing (Ten3+) CA1 axons are repelled by target-derived Lphn2, revealing that Lphn2- and Ten3-mediated heterophilic repulsion and Ten3-mediated homophilic attraction cooperate to control precise target selection of CA1 axons. In the lateral network, Lphn2-expressing (Lphn2+) CA1 axons are confined to Lphn2+ targets via repulsion from Ten3+ targets. Our findings demonstrate that assembly of parallel hippocampal networks follows a "Ten3→Ten3, Lphn2→Lphn2" rule instructed by reciprocal repulsions.


Assuntos
Orientação de Axônios , Axônios/fisiologia , Região CA1 Hipocampal/fisiologia , Hipocampo/fisiologia , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores de Peptídeos/metabolismo , Animais , Região CA1 Hipocampal/citologia , Córtex Entorrinal/fisiologia , Feminino , Hipocampo/citologia , Ligantes , Masculino , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos , Proteínas do Tecido Nervoso/genética , Vias Neurais , Receptores de Peptídeos/genética , Transcriptoma
19.
J Med Microbiol ; 70(6)2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34115583

RESUMO

Introduction. Leishmaniasis is a neglected tropical and subtropical disease caused by over 20 protozoan species.Hypothesis. Treatment of this complex disease with traditional synthetic drugs is a major challenge worldwide. Natural constituents are unique candidates for future therapeutic development.Aim. This study aimed to assess the in vivo anti-leishmanial effect of the Gossypium hirsutum extract, and its fractions compared to the standard drug (Glucantime, MA) in a murine model and explore the mechanism of action.Methodology. Footpads of BALB/c mice were infected with stationary phase promastigotes and treated topically and intraperitoneally with G. hirsutum extract, its fractions, or Glucantime, 4 weeks post-infection. The extract and fractions were prepared using the Soxhlet apparatus with chloroform followed by the column procedure.Results. The crude extract significantly decreased the footpad parasite load and lesion size compared to the untreated control group (P<0.05), as revealed by dilution assay, quantitative real-time PCR, and histopathological analyses. The primary mode of action involved an immunomodulatory role towards the Th1 response in the up-regulation of IFN-γ and IL-12 and the suppression of IL-10 gene expression profiling against cutaneous leishmaniasis caused by Leishmania major.Conclusion. This finding suggests that the extract possesses multiple combinatory effects of diverse bioactive phytochemical compositions that exert its mechanisms of action through agonistic-synergistic interactions. The topical extract formulation could be a suitable and unique candidate for future investigation and pharmacological development. Further studies are crucial to evaluate the therapeutic potentials of the extract alone and in combination with conventional drugs using clinical settings.


Assuntos
Antiprotozoários/uso terapêutico , Gossypium , Leishmania major/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Administração Tópica , Animais , Antiprotozoários/farmacologia , Feminino , Injeções Intraperitoneais , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-10/genética , Subunidade p40 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/metabolismo , Leishmania major/fisiologia , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/patologia , Leishmaniose Cutânea/fisiopatologia , Linfonodos/patologia , Antimoniato de Meglumina/administração & dosagem , Antimoniato de Meglumina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Baço/parasitologia , Baço/patologia , Células Th1/imunologia , Transcriptoma
20.
Int J Mol Sci ; 22(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34070162

RESUMO

During mRNA transcription, diverse RNA-binding proteins (RBPs) are recruited to RNA polymerase II (RNAP II) transcription machinery. These RBPs bind to distinct sites of nascent RNA to co-transcriptionally operate mRNA processing. Recent studies have revealed a close relationship between transcription and co-transcriptional RNA processing, where one affects the other's activity, indicating an essential role of protein-RNA interactions for the fine-tuning of mRNA production. Owing to their limited amount in cells, the detection of protein-RNA interactions specifically assembled on the transcribing RNAP II machinery still remains challenging. Currently, cross-linking and immunoprecipitation (CLIP) has become a standard method to detect in vivo protein-RNA interactions, although it requires a large amount of input materials. Several improved methods, such as infrared-CLIP (irCLIP), enhanced CLIP (eCLIP), and target RNA immunoprecipitation (tRIP), have shown remarkable enhancements in the detection efficiency. Furthermore, the utilization of an RNA editing mechanism or proximity labeling strategy has achieved the detection of faint protein-RNA interactions in cells without depending on crosslinking. This review aims to explore various methods being developed to detect endogenous protein-RNA interaction sites and discusses how they may be applied to the analysis of co-transcriptional RNA processing.


Assuntos
Imunoprecipitação/métodos , Processamento Pós-Transcricional do RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Sítios de Ligação , Perfilação da Expressão Gênica , Humanos , Imunoprecipitação/tendências , Ligação Proteica , RNA Polimerase II/metabolismo , Transcrição Genética , Transcriptoma
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...