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1.
Sci Rep ; 11(1): 17473, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471195

RESUMO

As for all newly-emergent pathogens, SARS-CoV-2 presents with a relative paucity of clinical information and experimental models, a situation hampering both the development of new effective treatments and the prediction of future outbreaks. Here, we find that a simple virus-free model, based on publicly available transcriptional data from human cell lines, is surprisingly able to recapitulate several features of the clinically relevant infections. By segregating cell lines (n = 1305) from the CCLE project on the base of their sole angiotensin-converting enzyme 2 (ACE2) mRNA content, we found that overexpressing cells present with molecular features resembling those of at-risk patients, including senescence, impairment of antibody production, epigenetic regulation, DNA repair and apoptosis, neutralization of the interferon response, proneness to an overemphasized innate immune activity, hyperinflammation by IL-1, diabetes, hypercoagulation and hypogonadism. Likewise, several pathways were found to display a differential expression between sexes, with males being in the least advantageous position, thus suggesting that the model could reproduce even the sex-related disparities observed in the clinical outcome of patients with COVID-19. Overall, besides validating a new disease model, our data suggest that, in patients with severe COVID-19, a baseline ground could be already present and, as a consequence, the viral infection might simply exacerbate a variety of latent (or inherent) pre-existing conditions, representing therefore a tipping point at which they become clinically significant.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , COVID-19/genética , Perfilação da Expressão Gênica/métodos , Regulação para Cima , COVID-19/imunologia , Linhagem Celular , Bases de Dados Genéticas , Feminino , Humanos , Imunidade Inata , Masculino , Modelos Biológicos , Modelos Teóricos , Caracteres Sexuais
2.
Anticancer Res ; 41(9): 4211-4214, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475040

RESUMO

BACKGROUND: Testicular cancer constitutes 1.0% of male cancer and typically carries a good prognosis. As far as we are aware, the role for hydrogen sulfide in testicular cancer and the level of hydrogen sulfide-synthesizing enzyme have never been addressed. Here we examined cystathionine gamma-lyase (CSE) expression in several germ-cell testicular tumors. MATERIALS AND METHODS: Tissue microarrays were employed to examine CSE expression in 32 benign testicular samples, 88 testicular seminomas, 34 embryonal carcinomas, 4 mature teratomas, and 16 yolk sac tumors, and CSE expression was compared to that seen in benign testicular tissue. RESULTS: Compared to benign testicular tissue, CSE expression was increased in all three types of testicular neoplasm but not in mature teratomas. Highest CSE expression was identified in embryonal carcinomas, which often show a relatively aggressive clinical course. CONCLUSION: For the first time, we show that CSE is increased in several common testicular germ-cell tumor types.


Assuntos
Carcinoma Embrionário/metabolismo , Cistationina gama-Liase/metabolismo , Tumor do Seio Endodérmico/metabolismo , Neoplasias Testiculares/metabolismo , Regulação para Cima , Estudos de Casos e Controles , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Seminoma , Análise Serial de Tecidos
3.
Anticancer Res ; 41(9): 4377-4385, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475057

RESUMO

BACKGROUND/AIM: Expression of pleckstrin homology-like domain family A member 2 (PHLDA2) has been reported to be suppressed or activated in several cases of malignant tumors. However, its apoptotic regulatory mechanism and role in gastric cancer are not understood. This study examined the role of PHLDA2 in apoptosis in gastric cancer. MATERIALS AND METHODS: We used cell culture, western blotting, semiquantitative reverse transcription polymerase chain reaction, MTT assays, and PHLDA2 knockdown with short hairpin RNA (shRNA). RESULTS: To identify the pathway associated with HGF-induced PHLDA2 up-regulation, the cells were treated with PI3-kinase inhibitor (LY294002), MEK inhibitor (PD098059), or p38 inhibitor (SB203580) and then analyzed by western blotting. HGF-mediated changes in PHLDA2 protein levels were only decreased by LY294002. PHLDA2-shRNA cells showed decreased levels of p53 and increased levels of pAKT. Furthermore, HGF-induced cell proliferation and in vitro invasion were increased in PHLDA2 knockdown cells and HGF-induced cell apoptosis was increased in PHLDA2 knockdown cells. CONCLUSION: PHLDA2 plays a role in gastric cancer tumorigenesis by inhibiting apoptosis through the PI3K/AKT pathway.


Assuntos
Fator de Crescimento de Hepatócito/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Gástricas/metabolismo , Regulação para Cima , Apoptose , Linhagem Celular Tumoral , Cromonas/farmacologia , Flavonoides/farmacologia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Imidazóis , Morfolinas/farmacologia , Proteínas Nucleares/genética , Análise de Sequência com Séries de Oligonucleotídeos , Piridinas
4.
Anticancer Res ; 41(9): 4463-4470, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475070

RESUMO

BACKGROUND/AIM: The treatment of advanced clear cell renal cell carcinoma (ccRCC) is based on stratification of patients according to prognosis (favorable, intermediate, and poor). The aim of the study was to improve prognostication by biomarkers involved in angiogenesis. PATIENTS AND METHODS: The study group consisted of 20 patients who underwent surgery for ccRCC. Gene expression analysis was peformed on a set of matched (primary tumor, metastasis, n=20+20) FFPE tissue samples. An additional analysis was done on expression data of 606 patients obtained from the TCGA Kidney Clear Cell Carcinoma (KIRC) database. Quantitative estimation of mRNA of selected genes (TaqMan human Angiogenesis Array, 97 genes) was performed by a real-time RT-PCR method with TaqMan® arrays. RESULTS: Using the Cox regression model, 4 genes (PDGFB, FGF4, EPHB2 and BAI1) were identified whose expression was related to progression-free interval (PFI). Further analysis using the Kaplan Meier method conclusively revealed the relationship of BAI1 expression to prognosis (both datasets). Patients with higher BAI1 expression had significantly shorter PFI and overall survival. CONCLUSION: We showed that tumor tissue BAI1 expression level is a prognostic marker in ccRCC. Therefore, this gene might be involved in a prognostic panel to improve scoring systems on which the management of metastatic ccRCC patients is based.


Assuntos
Proteínas Angiogênicas/genética , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Perfilação da Expressão Gênica/métodos , Neoplasias Renais/genética , Receptores Acoplados a Proteínas G/genética , Regulação para Cima , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/cirurgia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Análise de Regressão , Análise de Sobrevida
5.
Anticancer Res ; 41(9): 4489-4495, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475074

RESUMO

BACKGROUND/AIM: The chemokine receptors C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 7 (CCR7) play an important role in the invasion and metastasis of cancer. This study investigated the relationship between relative expression of CXCR4 and CCR7 mRNA, clinicopathological factors, and outcomes in patients with colorectal cancer (CRC). PATIENTS AND METHODS: We studied 202 patients who underwent surgery for CRC. The expression levels of CXCR4 and CCR7 mRNA in cancerous tissue were measured using quantitative real-time reverse-transcriptase polymerase chain reaction. RESULTS: High CCR7 mRNA expression levels in CRC tissues were positively associated with tumour size and were more frequently associated with cancer of the rectum than of the colon. Moreover, outcomes were significantly poorer in patients with high CCR7 mRNA expression than in those with low expression. On multivariate Cox regression analysis, a higher CCR7 mRNA expression level was a significant independent predictor of poorer overall survival in patients with CRC. CONCLUSION: Overexpression of CCR7 mRNA may be a useful independent prognostic factor in patients with CRC.


Assuntos
Neoplasias Colorretais/cirurgia , Perfilação da Expressão Gênica/métodos , Receptores CCR7/genética , Receptores CXCR4/genética , Regulação para Cima , Idoso , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Carga Tumoral
6.
BMC Plant Biol ; 21(1): 358, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348650

RESUMO

BACKGROUND: The South America pinworm, Tuta absoluta, is a destructive pest of tomato that causes important losses worldwide. Breeding of resistant/tolerant tomato cultivars could be an effective strategy for T. absoluta management but, despite the economic importance of tomato, very limited information is available about its response to this treat. To elucidate the defense mechanisms to herbivore feeding a comparative analysis was performed between a tolerant and susceptible cultivated tomato at both morphological and transcriptome level to highlight constitutive leaf barriers, molecular and biochemical mechanisms to counter the effect of T. absoluta attack. RESULTS: The tolerant genotype showed an enhanced constitutive barrier possibly as result of the higher density of trichomes and increased inducible reactions upon mild infestation thanks to the activation/repression of key transcription factors regulating genes involved in cuticle formation and cell wall strength as well as of antinutritive enzymes, and genes involved in the production of chemical toxins and bioactive secondary metabolites. CONCLUSIONS: Overall, our findings suggest that tomato resilience to the South America pinworm is achieved by a combined strategy between constitutive and induced defense system. A well-orchestrated modulation of plant transcription regulation could ensure a trade-off between defense needs and fitness costs. Our finding can be further exploited for developing T. absoluta tolerant cultivars, acting as important component of integrated pest management strategy for more sustainable production.


Assuntos
Regulação da Expressão Gênica de Plantas , Lycopersicon esculentum/genética , Doenças das Plantas/genética , Folhas de Planta/genética , Transcriptoma , Animais , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Interações Hospedeiro-Parasita , Larva/fisiologia , Lycopersicon esculentum/metabolismo , Lycopersicon esculentum/parasitologia , Mariposas/fisiologia , Doenças das Plantas/parasitologia , Folhas de Planta/metabolismo , Folhas de Planta/parasitologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , RNA-Seq/métodos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Tricomas/genética , Tricomas/metabolismo , Tricomas/parasitologia
7.
Sci Adv ; 7(34)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34407940

RESUMO

Novel coronavirus disease 2019 (COVID-19) severity is highly variable, with pediatric patients typically experiencing less severe infection than adults and especially the elderly. The basis for this difference is unclear. We find that mRNA and protein expression of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19, increases with advancing age in distal lung epithelial cells. However, in humans, ACE2 expression exhibits high levels of intra- and interindividual heterogeneity. Further, cells infected with SARS-CoV-2 experience endoplasmic reticulum stress, triggering an unfolded protein response and caspase-mediated apoptosis, a natural host defense system that halts virion production. Apoptosis of infected cells can be selectively induced by treatment with apoptosis-modulating BH3 mimetic drugs. Notably, epithelial cells within young lungs and airways are more primed to undergo apoptosis than those in adults, which may naturally hinder virion production and support milder COVID-19 severity.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , Apoptose/genética , COVID-19/genética , Perfilação da Expressão Gênica/métodos , Fatores Etários , Idoso , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/metabolismo , COVID-19/virologia , Células Cultivadas , Chlorocebus aethiops , Feminino , Humanos , Lactente , Pulmão/citologia , Pulmão/metabolismo , Pulmão/virologia , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Células Vero , Internalização do Vírus
8.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445112

RESUMO

Brassinosteroids (BRs) are steroid phytohormones that are known to regulate plant growth and nutrient uptake and distribution. However, how BRs regulate nutrient uptake and balance in legume species is not fully understood. Here, we show that optimal BR levels are required for soybean (Glycine max L.) seedling growth, as treatments with both 24-epicastasterone (24-epiCS) and the BR biosynthesis inhibitor propiconazole (PPZ) inhibit root growth, including primary root elongation and lateral root formation and elongation. Specifically, 24-epiCS and PPZ reduced the total phosphorus and potassium levels in the shoot and affected several minor nutrients, such as magnesium, iron, manganese, and molybdenum. A genome-wide transcriptome analysis identified 3774 and 4273 differentially expressed genes in the root tip after brassinolide and PPZ treatments, respectively. The gene ontology (GO) analysis suggested that genes related to "DNA-replication", "microtubule-based movement", and "plant-type cell wall organization" were highly responsive to the brassinolide and PPZ treatments. Furthermore, consistent with the effects on the nutrient concentrations, corresponding mineral transporters were found to be regulated by BR levels, including the GmPHT1s, GmKTs, GmVIT2, GmZIPs, and GmMOT1 genes. Our study demonstrates that optimal BR levels are important for growth and mineral nutrient homeostasis in soybean seedlings.


Assuntos
Brassinosteroides/metabolismo , Homeostase/fisiologia , Minerais/metabolismo , Nutrientes/metabolismo , Soja/crescimento & desenvolvimento , Soja/metabolismo , Colestanóis/metabolismo , Fabaceae/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas/fisiologia , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Plântula/metabolismo , Esteroides Heterocíclicos/metabolismo
9.
Int J Mol Sci ; 22(16)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445782

RESUMO

Spodoptera exigua is a worldwide pest afflicting edible vegetables and has developed varying levels of resistance to insecticides. Methoxyfenozide (MET), an ecdysteroid agonist, is effective against lepidopteran pests such as S. exigua. However, the mechanism of MET to S. exigua remains unclear. In this study, we analyzed the expression patterns of genes related to the ecdysone signaling pathway in transcriptome data treated with sublethal doses of MET and analyzed how expression levels of key genes affect the toxicity of MET on S. exigua. Our results demonstrated that 2639 genes were up-regulated and 2512 genes were down-regulated in S. exigua treated with LC30 of MET. Of these, 15 genes were involved in the ecdysone signaling pathway. qPCR results demonstrated that ecdysone receptor A (EcRA) expression levels significantly increased in S. exigua when treated with different doses of MET, and that the RNAi-mediated silencing of EcRA significantly increased mortality to 55.43% at 72 h when L3 S. exigua larvae were exposed to MET at the LC30 dose. Additionally, knocking down EcRA suppressed the most genes expressed in the ecdysone signaling pathway. The combination of MET and dsEcRA affected the expression of E74 and enhanced the expression of TREA. These results demonstrate that the adverse effects of sublethal MET disturb the ecdysone signaling pathway in S. exigua, and EcRA is closely related to MET toxic effect. This study increases our collective understanding of the mechanisms of MET in insect pests.


Assuntos
Ecdisona/genética , Hidrazinas/farmacologia , Hormônios Juvenis/farmacologia , Interferência de RNA/fisiologia , Transdução de Sinais/efeitos dos fármacos , Spodoptera/efeitos dos fármacos , Transcriptoma/genética , Animais , Perfilação da Expressão Gênica/métodos , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Larva/genética , Receptores de Esteroides/genética , Spodoptera/genética
10.
Int J Mol Sci ; 22(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34445369

RESUMO

Annexin (Ann) is a polygenic, evolutionarily conserved, calcium-dependent and phospholipid-binding protein family, which plays key roles in plant growth, development, and stress response. However, a comprehensive understanding of CaAnn genes of pepper (Capsicum annuum) at the genome-wide level is limited. Based on the available pepper genomic information, we identified 15 members of the CaAnn gene family. Phylogenetic analysis showed that CaAnn proteins could be categorized into four different orthologous groups. Real time quantitative RT-PCR analysis showed that the CaAnn genes were tissue-specific and were widely expressed in pepper leaves after treatments with cold, salt, and drought, as well as exogenously applied MeJA and ABA. In addition, the function of CaAnn9 was further explored using the virus-induced gene silencing (VIGS) technique. CaAnn9-silenced pepper seedlings were more sensitive to salt stress, reflected by the degradation of chlorophyll, the accumulation of reactive oxygen species (ROS), and the decrease of antioxidant defense capacity. This study provides important information for further study of the role of pepper CaAnn genes and their coding proteins in growth, development, and environmental responses.


Assuntos
Anexinas/genética , Capsicum/crescimento & desenvolvimento , Perfilação da Expressão Gênica/métodos , Tolerância ao Sal , Ácido Abscísico/farmacologia , Acetatos/farmacologia , Capsicum/efeitos dos fármacos , Capsicum/genética , Ciclopentanos/farmacologia , Evolução Molecular , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Especificidade de Órgãos , Oxilipinas/farmacologia , Filogenia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/genética , Sequenciamento Completo do Genoma
11.
Int J Mol Sci ; 22(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34445387

RESUMO

Prostate cancer (PCa) is the leading cause of cancer-associated mortality in men, and new biomarkers are still needed. The expression pattern and protein tissue localization of proteoglycans of the syndecan family (SDC 1-4) and syntenin-1 (SDCBP) were determined in normal and prostatic tumor tissue from two genetically engineered mouse models and human prostate tumors. Studies were validated using SDC 1-4 and SDCBP mRNA levels and patient survival data from The Cancer Genome Atlas and CamCAP databases. RNAseq showed increased expression of Sdc1 in Pb-Cre4/Ptenf/f mouse Pca and upregulation of Sdc3 expression and downregulation of Sdc2 and Sdc4 when compared to the normal prostatic tissue in Pb-Cre4/Trp53f/f-;Rb1f/f mouse tumors. These changes were confirmed by immunohistochemistry. In human PCa, SDC 1-4 and SDCBP immunostaining showed variable localization. Furthermore, Kaplan-Meier analysis showed that patients expressing SDC3 had shorter prostate-specific survival than those without SDC3 expression (log-rank test, p = 0.0047). Analysis of the MSKCC-derived expression showed that SDC1 and SDC3 overexpression is predictive of decreased biochemical recurrence-free survival (p = 0.0099 and p = 0.045, respectively), and SDC4 overexpression is predictive of increased biochemical recurrence-free survival (p = 0.035). SDC4 overexpression was associated with a better prognosis, while SDC1 and SDC3 were associated with more aggressive tumors and a worse prognosis.


Assuntos
Perfilação da Expressão Gênica/métodos , Neoplasias da Próstata/patologia , Sindecana-1/genética , Sindecana-3/genética , Sindecana-4/genética , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Transplante de Neoplasias , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Análise Serial de Proteínas , Análise de Sequência de RNA , Análise de Sobrevida , Sindecana-1/metabolismo , Sindecana-3/metabolismo , Sindecana-4/metabolismo , Sinteninas/genética , Sinteninas/metabolismo
12.
Medicine (Baltimore) ; 100(32): e26922, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397934

RESUMO

BACKGROUND: As an anticancer gene, microRNA-145 (miRNA-145) inhibits the growth, migration, and invasion of cancer cells, and inhibits tumorigenesis by targeting various genes that are abnormally expressed in tumors. However, whether miRNA-145 can be applied as a biomarker for potential prognosis of ovarian cancer still remains controversial. Therefore, this study further explored the prognostic value and mechanism of miRNA-145 in ovarian cancer through meta-analysis and bioinformatics analysis. METHODS: Eligible studies were identified by searching the China National Knowledge Infrastructure, Chinese Biomedical literature Database, Chinese Scientific and Journal Database, Wan Fang database, PubMed, EMBASE, and Web of Science up to July 2021. Pooled hazard ratios with 95% confidence intervals for patient survival were calculated to investigate the effects of miRNA-145 on the prognosis of ovarian cancer. Survival curves of differential expression of miRNA-145 were analyzed by Oncomir. The target genes of miRNA-145 were predicted by miRTARbase and Diana-Tarbase V7.0 database. Enrichr database was applied to analyze the target genes by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Protein-protein interaction network of target genes was constructed from STRING database. Cytoscape software was used to screen the hub genes to meet the requirements. The Gene Expression Profiling Interactive Analysis database was applied to analyze the survival outcomes of hub genes. RESULTS: The results of this meta-analysis would be submitted to peer-reviewed journals for publication. CONCLUSION: This study provides high-quality evidence to support the relationship between miRNA-145 expression and ovarian cancer prognosis. Through bioinformatics analysis, we further explored the mechanism of miRNA-145 in ovarian cancer and related pathways.


Assuntos
Carcinoma Epitelial do Ovário/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Ovarianas/genética , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário/metabolismo , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , MicroRNAs/biossíntese , Neoplasias Ovarianas/metabolismo , Prognóstico
13.
Medicine (Baltimore) ; 100(30): e26582, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397688

RESUMO

BACKGROUND: Tuberculosis (TB) is a global health problem that brings us numerous difficulties. Diverse genetic factors play a significant role in the progress of TB disease. However, still no key genes for TB susceptibility have been reported. This study aimed to identify the key genes of TB through comprehensive bioinformatics analysis. METHODS: The series microarray datasets from the gene expression omnibus (GEO) database were analyzed. We used the online tool GEO2R to filtrate differentially expressed genes (DEGs) between TB and health control. Database for annotation can complete gene ontology function analysis as well as Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Protein-protein interaction (PPI) networks of DEGs were established by STRING online tool and visualized by Cytoscape software. Molecular Complex Detection can complete the analysis of modules in the PPI networks. Finally, the significant hub genes were confirmed by plug-in Genemania of Cytoscape, and verified by the verification cohort and protein test. RESULTS: There are a total of 143 genes were confirmed as DEGs, containing 48 up-regulated genes and 50 down-regulated genes. The gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis show that upregulated DEGs were associated with cancer and phylogenetic, whereas downregulated DEGs mainly concentrate on inflammatory immunity. PPI networks show that signal transducer and activator of transcription 1 (STAT1), guanylate binding protein 5 (GBP5), 2'-5'-oligoadenylate synthetase 1 (OAS1), catenin beta 1 (CTNNB1), and guanylate binding protein 1 (GBP1) were identified as significantly different hub genes. CONCLUSION: We conclude that these genes, including TAT1, GBP5, OAS1, CTNNB1, GBP1 are a candidate as potential core genes in TB and treatment of TB in the future.


Assuntos
Tuberculose/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Humanos , Análise em Microsséries
14.
Nature ; 596(7871): 211-220, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34381231

RESUMO

Deciphering the principles and mechanisms by which gene activity orchestrates complex cellular arrangements in multicellular organisms has far-reaching implications for research in the life sciences. Recent technological advances in next-generation sequencing- and imaging-based approaches have established the power of spatial transcriptomics to measure expression levels of all or most genes systematically throughout tissue space, and have been adopted to generate biological insights in neuroscience, development and plant biology as well as to investigate a range of disease contexts, including cancer. Similar to datasets made possible by genomic sequencing and population health surveys, the large-scale atlases generated by this technology lend themselves to exploratory data analysis for hypothesis generation. Here we review spatial transcriptomic technologies and describe the repertoire of operations available for paths of analysis of the resulting data. Spatial transcriptomics can also be deployed for hypothesis testing using experimental designs that compare time points or conditions-including genetic or environmental perturbations. Finally, spatial transcriptomic data are naturally amenable to integration with other data modalities, providing an expandable framework for insight into tissue organization.


Assuntos
Perfilação da Expressão Gênica/métodos , Especificidade de Órgãos/genética , Transcriptoma , Animais , Análise de Dados , Doença/genética , Humanos , Transcrição Genética/genética
15.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445398

RESUMO

Gibberellins (GAs) are an important group of phytohormones associated with diverse growth and developmental processes, including cell elongation, seed germination, and secondary growth. Recent genomic and genetic analyses have advanced our knowledge of GA signaling pathways and related genes in model plant species. However, functional genomics analyses of GA signaling pathways in Panax ginseng, a perennial herb, have rarely been carried out, despite its well-known economical and medicinal importance. Here, we conducted functional characterization of GA receptors and investigated their physiological roles in the secondary growth of P. ginseng storage roots. We found that the physiological and genetic functions of P. ginseng gibberellin-insensitive dwarf1s (PgGID1s) have been evolutionarily conserved. Additionally, the essential domains and residues in the primary protein structure for interaction with active GAs and DELLA proteins are well-conserved. Overexpression of PgGID1s in Arabidopsis completely restored the GA deficient phenotype of the Arabidopsis gid1a gid1c (atgid1a/c) double mutant. Exogenous GA treatment greatly enhanced the secondary growth of tap roots; however, paclobutrazol (PCZ), a GA biosynthetic inhibitor, reduced root growth in P. ginseng. Transcriptome profiling of P. ginseng roots revealed that GA-induced root secondary growth is closely associated with cell wall biogenesis, the cell cycle, the jasmonic acid (JA) response, and nitrate assimilation, suggesting that a transcriptional network regulate root secondary growth in P. ginseng. These results provide novel insights into the mechanism controlling secondary root growth in P. ginseng.


Assuntos
Perfilação da Expressão Gênica/métodos , Giberelinas/farmacologia , Panax/crescimento & desenvolvimento , Receptores de Superfície Celular/genética , Evolução Molecular , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Mutação com Perda de Função , Panax/genética , Proteínas de Plantas/genética , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Domínios Proteicos , Receptores de Superfície Celular/química , Análise de Sequência de RNA , Transdução de Sinais/efeitos dos fármacos , Triazóis/farmacologia
16.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445418

RESUMO

Central pattern generators produce rhythmic behaviors independently of sensory input; however, their outputs can be modulated by neuropeptides, thereby allowing for functional flexibility. We investigated the effects of C-type allatostatins (AST-C) on the cardiac ganglion (CG), which is the central pattern generator that controls the heart of the American lobster, Homarus americanus, to identify the biological mechanism underlying the significant variability in individual responses to AST-C. We proposed that the presence of multiple receptors, and thus differential receptor distribution, was at least partly responsible for this observed variability. Using transcriptome mining and PCR-based cloning, we identified four AST-C receptors (ASTCRs) in the CG; we then characterized their cellular localization, binding potential, and functional activation. Only two of the four receptors, ASTCR1 and ASTCR2, were fully functional GPCRs that targeted to the cell surface and were activated by AST-C peptides in our insect cell expression system. All four, however, were amplified from CG cDNAs. Following the confirmation of ASTCR expression, we used physiological and bioinformatic techniques to correlate receptor expression with cardiac responses to AST-C across individuals. Expression of ASTCR1 in the CG showed a negative correlation with increasing contraction amplitude in response to AST-C perfusion through the lobster heart, suggesting that the differential expression of ASTCRs within the CG is partly responsible for the specific physiological response to AST-C exhibited by a given individual lobster.


Assuntos
Perfilação da Expressão Gênica/métodos , Nephropidae/genética , Neuropeptídeos/farmacologia , Receptores de Neuropeptídeos/genética , Receptores de Neuropeptídeos/metabolismo , Animais , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/metabolismo , Sistema Cardiovascular/metabolismo , Membrana Celular/metabolismo , Clonagem Molecular , Mineração de Dados , Bases de Dados Genéticas , Regulação da Expressão Gênica/efeitos dos fármacos , Miocárdio/metabolismo , Nephropidae/efeitos dos fármacos , Nephropidae/metabolismo , Análise de Sequência de RNA , Células Sf9 , Distribuição Tecidual
17.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445424

RESUMO

Biomarkers for predicting individual response to radiation and for dose verification are needed to improve radiotherapy. A biomarker should optimally show signal fidelity, meaning that its level is stable and proportional to the absorbed dose. miRNA levels in human blood serum were suggested as promising biomarkers. The aim of the present investigation was to test the miRNA biomarker in leukocytes of breast cancer patients undergoing external beam radiotherapy. Leukocytes were isolated from blood samples collected prior to exposure (control); on the day when a total dose of 2 Gy, 10 Gy, or 20 Gy was reached; and one month after therapy ended (46-50 Gy in total). RNA sequencing was performed and univariate analysis was used to analyse the effect of the radiation dose on the expression of single miRNAs. To check if combinations of miRNAs can predict absorbed dose, a multinomial logistic regression model was built using a training set from eight patients (representing 40 samples) and a validation set with samples from the remaining eight patients (15 samples). Finally, Broadside, an explorative interaction mining tool, was used to extract sets of interacting miRNAs. The most prominently increased miRNA was miR-744-5p, followed by miR-4461, miR-34a-5p, miR-6513-5p, miR-1246, and miR-454-3p. Decreased miRNAs were miR-3065-3p, miR-103a-2-5p, miR-30b-3p, and miR-5690. Generally, most miRNAs showed a relatively strong inter-individual variability and different temporal patterns over the course of radiotherapy. In conclusion, miR-744-5p shows promise as a stable miRNA marker, but most tested miRNAs displayed individual signal variability which, at least in this setting, may exclude them as sensitive biomarkers of radiation response.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/radioterapia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , MicroRNAs/genética , Idoso , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Fracionamento da Dose de Radiação , Feminino , Humanos , Pessoa de Meia-Idade , Análise de Sequência de RNA , Resultado do Tratamento , Regulação para Cima
18.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445494

RESUMO

Despite significant advances in treatment of acute coronary syndromes (ACS) many subjects still develop heart failure due to significantly reduced ejection fraction. Currently, there are no commonly available treatment strategies that replace the infarcted/dysfunctional myocardium. Therefore, understanding the mechanisms that control the regeneration of the heart muscle is important. The development of new coronary vessels plays a pivotal role in cardiac regeneration. Employing microarray expression assays and RT-qPCR validation expression pattern of genes in long-term primary cultured cells isolated form the right atrial appendage (RAA) and right atrium (RA) was evaluated. After using DAVID software, it indicated the analysis expression profiles of genes involved in ontological groups such as: "angiogenesis", "blood vessel morphogenesis", "circulatory system development", "regulation of vasculature development", and "vasculature development" associated with the process of creation new blood vessels. The performed transcriptomic comparative analysis between two different compartments of the heart muscle allowed us to indicate the presence of differences in the expression of key transcripts depending on the cell source. Increases in culture intervals significantly increased expression of SFRP2, PRRX1 genes and some other genes involved in inflammatory process, such as: CCL2, IL6, and ROBO1. Moreover, the right atrial appendage gene encoding lysyl oxidase (LOX) showed much higher expression compared to the pre-cultivation state.


Assuntos
Vasos Coronários/crescimento & desenvolvimento , Perfilação da Expressão Gênica/métodos , Desenvolvimento Muscular , Miocárdio/citologia , Animais , Células Cultivadas , Vasos Coronários/química , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Miocárdio/química , Análise de Sequência com Séries de Oligonucleotídeos , Cultura Primária de Células , Suínos , Sequenciamento Completo do Exoma
19.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445522

RESUMO

Crocetin is an apocarotenoid formed from the oxidative cleavage of zeaxanthin, by the carotenoid cleavage enzymes CCD2 (in Crocus species) and specific CCD4 enzymes in Buddleja davidii and Gardenia jasminoides. Crocetin accumulates in the stigma of saffron in the form of glucosides and crocins, which contain one to five glucose molecules. Crocetin glycosylation was hypothesized to involve at least two enzymes from superfamily 1 UDP-sugar dependent glycosyltransferases. One of them, UGT74AD1, produces crocins with one and two glucose molecules, which are substrates for a second UGT, which could belong to the UGT79, 91, or 94 families. An in silico search of Crocus transcriptomes revealed six candidate UGT genes from family 91. The transcript profiles of one of them, UGT91P3, matched the metabolite profile of crocin accumulation, and were co-expressed with UGT74AD1. In addition, both UGTs interact in a two-hybrid assay. Recombinant UGT91P3 produced mostly crocins with four and five glucose molecules in vitro, and in a combined transient expression assay with CCD2 and UGT74AD1 enzymes in Nicotiana benthamiana. These results suggest a role of UGT91P3 in the biosynthesis of highly glucosylated crocins in saffron, and that it represents the last missing gene in crocins biosynthesis.


Assuntos
Carotenoides/metabolismo , Crocus/enzimologia , Perfilação da Expressão Gênica/métodos , Glicosiltransferases/genética , Vias Biossintéticas , Simulação por Computador , Crocus/química , Crocus/genética , Regulação da Expressão Gênica de Plantas , Glicosilação , Proteínas de Plantas/genética , Técnicas do Sistema de Duplo-Híbrido
20.
Sci Rep ; 11(1): 17351, 2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34456333

RESUMO

Coronavirus disease 2019 (COVID-19) is raging worldwide. This potentially fatal infectious disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the complete mechanism of COVID-19 is not well understood. Therefore, we analyzed gene expression profiles of COVID-19 patients to identify disease-related genes through an innovative machine learning method that enables a data-driven strategy for gene selection from a data set with a small number of samples and many candidates. Principal-component-analysis-based unsupervised feature extraction (PCAUFE) was applied to the RNA expression profiles of 16 COVID-19 patients and 18 healthy control subjects. The results identified 123 genes as critical for COVID-19 progression from 60,683 candidate probes, including immune-related genes. The 123 genes were enriched in binding sites for transcription factors NFKB1 and RELA, which are involved in various biological phenomena such as immune response and cell survival: the primary mediator of canonical nuclear factor-kappa B (NF-κB) activity is the heterodimer RelA-p50. The genes were also enriched in histone modification H3K36me3, and they largely overlapped the target genes of NFKB1 and RELA. We found that the overlapping genes were downregulated in COVID-19 patients. These results suggest that canonical NF-κB activity was suppressed by H3K36me3 in COVID-19 patient blood.


Assuntos
COVID-19/genética , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Histonas/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Fator de Transcrição RelA/metabolismo , Sítios de Ligação , COVID-19/metabolismo , Estudos de Casos e Controles , Epigênese Genética , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Aprendizado de Máquina , Transdução de Sinais
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