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1.
J Microbiol ; 57(9): 781-794, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31452043

RESUMO

The phytopathogenic Burkholderia species B. glumae and B. plantarii are the causal agents of bacterial wilt, grain rot, and seedling blight, which threaten the rice industry globally. Toxoflavin and tropolone are produced by these phytopathogens and are considered the most hostile biohazards with a broad spectrum of target organisms. However, despite their nonspecific toxicity, the effects of toxoflavin and tropolone on bacteria remain unknown. RNA-seq based transcriptome analysis was employed to determine the genome-wide expression patterns under phytotoxin treatment. Expression of 2327 and 830 genes was differentially changed by toxoflavin and tropolone, respectively. Enriched biological pathways reflected the down-regulation of oxidative phosphorylation and ribosome function, beginning with the inhibition of membrane biosynthesis and nitrogen metabolism under oxidative stress or iron starvation. Conversely, several systems such as bacterial chemotaxis, flagellar assembly, biofilm formation, and sulfur/taurine transporters were highly expressed as countermeasures against the phytotoxins. In addition, our findings revealed that three hub genes commonly induced by both phytotoxins function as the siderophore enterobactin, an iron-chelator. Our study provides new insights into the effects of phytotoxins on bacteria for better understanding of the interactions between phytopathogens and other microorganisms. These data will also be applied as a valuable source in subsequent applications against phytotoxins, the major virulence factor.


Assuntos
Antibacterianos/toxicidade , Burkholderia/química , Proteínas de Escherichia coli/genética , Escherichia coli/efeitos dos fármacos , Doenças das Plantas/microbiologia , Pirimidinonas/toxicidade , Triazinas/toxicidade , Tropolona/toxicidade , Antibacterianos/metabolismo , Burkholderia/metabolismo , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Oryza/microbiologia , Pirimidinonas/metabolismo , Transcriptoma/efeitos dos fármacos , Triazinas/metabolismo , Tropolona/metabolismo
2.
Cancer Treat Rev ; 77: 57-66, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31279169

RESUMO

One of the major complications that patients experience during pharmacological treatment is the occurrence of adverse drug reactions (ADRs). The most affected organs are the liver, kidney, heart and the gastrointestinal-immune system. In comparison to the other organs, less progress has been made on human-relevant prediction of drug-induced intestinal toxicity, evidencing current large data gaps. The most widely used drugs that are associated with intestinal damage include chemotherapeutics, such as 5-Fluorouracil or Tyrosine Kinase Inhibitors (TKIs), as well as non-steroidal anti-inflammatory drugs (NSAIDs). Chemotherapeutics are regarded as inducers of acute intestinal toxicity whereas NSAIDs are associated with chronic inflammation of the intestine. In view of the fact that only a few studies have been dedicated to studying cellular and genomic responses in relation to drug-induced intestinal ADRs, little is known about how intestinal toxicity develops after exposure to such drugs or which molecular mechanisms are involved. Therefore, new models and experiments are required to establish transcriptomic responses and alterations of molecular markers induced by different medicines. This review summarizes the available information about transcriptomic responses and biomarkers of toxicity induced by 5-FU, NSAIDS or TKIs in different experimental models. Future investigation should address the challenges in predicting intestinal toxicity induced by drugs and unveil specific gene expression profiles that can be applied in the development of safer drugs.


Assuntos
Enteropatias/induzido quimicamente , Enteropatias/genética , Transcriptoma/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/efeitos adversos , Fluoruracila/efeitos adversos , Humanos , Inibidores de Proteínas Quinases/efeitos adversos
3.
Medicine (Baltimore) ; 98(26): e15872, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261495

RESUMO

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer accounts for ∼20% of invasive breast cancers and is associated with poor prognostics. The recent outcome of HER2+ breast cancer treatment has been vastly improved owing to the application of antibody-targeted therapies. Trastuzumab (Herceptin) is a monoclonal antibody designed to target HER2+ breast cancer cells. In addition to improved survival in the adjuvant treatment of HER2+ breast cancer, trastuzumab treatment has also been associated with cardiotoxicity side effect. However, the molecular mechanisms of trastuzumab action and trastuzumab-mediated cardiotoxicity are still not fully understood. Previous research utilized bulk transcriptomics analysis to study the underlining mechanisms, which relied on averaging molecular signals from bulk tumor samples and might have overlooked key expression features within breast cancer tumor. In contrast to previous research, we compared the single cancer cell level transcriptome profile between trastuzumab-treated and nontreated patients to reveal a more in-depth transcriptome profile. A total of 461 significantly differential expressed genes were identified, including previously defined and novel gene expression signatures. In addition, we found that trastuzumab-enhanced MGP gene expression could be used as prognostics marker for longer patient survival in breast invasive carcinoma patients, and validated our finding using TCGA (The Cancer Genome Atlas) breast cancer dataset. Moreover, our study revealed a 48-gene expression signature that is associated with cell death of cardiomyocytes, which could be used as early biomarkers for trastuzumab-mediated cardiotoxicity. This work is the first study to look at single cell level transcriptome profile of trastuzumab-treated patients, providing a new understanding of the molecular mechanism(s) of trastuzumab action and trastuzumab-induced cardiotoxicity side effects.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptor ErbB-2/metabolismo , Transcriptoma/efeitos dos fármacos , Trastuzumab/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/epidemiologia , Proteínas de Ligação ao Cálcio/metabolismo , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Ductal de Mama/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Projetos Piloto , Prognóstico , RNA Mensageiro/metabolismo , Análise de Sequência de RNA , Análise de Célula Única , Análise de Sobrevida
4.
Plant Sci ; 285: 239-247, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203889

RESUMO

Foxtail millet (Setaria italica) is a nutrient-rich food source traditionally grown in arid and semi-arid areas, as it is well adapted to drought climate. Yet there is limited information as how the crop responses to the changing climate. In order to investigate the response of foxtail millet to elevated [CO2] and the underlying mechanism, the crop was grown at ambient [CO2] (400 µmol mol-1) and elevated [CO2] (600 µmol mol-1) in an open-top chamber (OTC) experimental facility in North China. The changes in leaf photosynthesis, chlorophyll fluorescence, biomass, yield and global gene expression in response to elevated [CO2] were determined. Despite foxtail millet being a C4 photosynthetic crop, photosynthetic rates (PN) and intrinsic water-use efficiency (WUEi), were increased under elevated [CO2]. Similarly, grain yield and above-ground biomass also significantly increased (P <  0.05) for the two years of experimentation under elevated [CO2]. Increases in seeds and tiller number, spike and stem weight were the main contributors to the increased grain yield and biomass. Using transcriptomic analyses, this study further identified some genes which play a role in cell wall reinforcement, shoot initiation, stomatal conductance, carbon fixation, glycolysis / gluconeogenesis responsive to elevated [CO2]. Changes in these genes reduced plant height, increased stem diameters, and promote CO2 fixation. Higher photosynthetic rates at elevated [CO2] demonstrated that foxtail millet was not photosynthetically saturated at elevated [CO2] and its photosynthesis response to elevated [CO2] were analogous to C3 plants.


Assuntos
Fotossíntese/efeitos dos fármacos , Setaria (Planta)/efeitos dos fármacos , Biomassa , Dióxido de Carbono/metabolismo , Clorofila/metabolismo , Produção Agrícola , Sequenciamento de Nucleotídeos em Larga Escala , Reação em Cadeia da Polimerase em Tempo Real , Setaria (Planta)/genética , Setaria (Planta)/crescimento & desenvolvimento , Setaria (Planta)/metabolismo , Transcriptoma/efeitos dos fármacos
5.
Nat Commun ; 10(1): 2645, 2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31201315

RESUMO

Lettuce downy mildew caused by Bremia lactucae is the most important disease of lettuce globally. This oomycete is highly variable and rapidly overcomes resistance genes and fungicides. The use of multiple read types results in a high-quality, near-chromosome-scale, consensus assembly. Flow cytometry plus resequencing of 30 field isolates, 37 sexual offspring, and 19 asexual derivatives from single multinucleate sporangia demonstrates a high incidence of heterokaryosis in B. lactucae. Heterokaryosis has phenotypic consequences on fitness that may include an increased sporulation rate and qualitative differences in virulence. Therefore, selection should be considered as acting on a population of nuclei within coenocytic mycelia. This provides evolutionary flexibility to the pathogen enabling rapid adaptation to different repertoires of host resistance genes and other challenges. The advantages of asexual persistence of heterokaryons may have been one of the drivers of selection that resulted in the loss of uninucleate zoospores in multiple downy mildews.


Assuntos
Núcleo Celular/genética , Interações Hospedeiro-Patógeno/genética , Alface/microbiologia , Oomicetos/genética , Doenças das Plantas/microbiologia , Núcleo Celular/efeitos dos fármacos , Resistência à Doença/genética , Fungicidas Industriais/farmacologia , Genômica , Alface/genética , Oomicetos/citologia , Oomicetos/patogenicidade , Seleção Genética/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética , Virulência/genética
6.
Nat Commun ; 10(1): 2691, 2019 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-31217428

RESUMO

The MUSASHI (MSI) family of RNA binding proteins (MSI1 and MSI2) contribute to a wide spectrum of cancers including acute myeloid leukemia. We find that the small molecule Ro 08-2750 (Ro) binds directly and selectively to MSI2 and competes for its RNA binding in biochemical assays. Ro treatment in mouse and human myeloid leukemia cells results in an increase in differentiation and apoptosis, inhibition of known MSI-targets, and a shared global gene expression signature similar to shRNA depletion of MSI2. Ro demonstrates in vivo inhibition of c-MYC and reduces disease burden in a murine AML leukemia model. Thus, we identify a small molecule that targets MSI's oncogenic activity. Our study provides a framework for targeting RNA binding proteins in cancer.


Assuntos
Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Leucemia Experimental/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Pteridinas/farmacologia , Proteínas de Ligação a RNA/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Perfilação da Expressão Gênica , Humanos , Leucemia Experimental/sangue , Leucemia Mieloide Aguda/sangue , Masculino , Camundongos , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-myc/metabolismo , Pteridinas/uso terapêutico , RNA/metabolismo , Motivo de Reconhecimento de RNA/efeitos dos fármacos , RNA Interferente Pequeno/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Transcriptoma/efeitos dos fármacos , Células Tumorais Cultivadas
7.
Toxicol Lett ; 312: 34-44, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31059760

RESUMO

Inflammation is one of the factors that may increase the sensitivity of hepatic cells to acetaminophen (APAP) induced toxicity. To investigate the mechanisms, we exposed 3-dimensional (3D) Human Liver Microtissues, a co-culture of primary human hepatocytes (PHH) and Kupffer cells (KCs), to 0, 0.5 (low), 5 (median) and 10 mM (high dose) APAP for 24 h, with/without lipopolysaccharide (LPS). Microarray-technology was used to evaluate the transcriptome changes. In the presence of LPS, the median-dose of APAP is sufficient to inhibit the expression of respiratory chain- and antioxidant-related genes, suggesting the involvement of reactive oxygen species (ROS) and oxidative stress. Furthermore, the median- and high-dose of APAP inhibited the expression of Fc fragment receptor (FcγR)-coding genes, regardless of the presence of LPS. The toll-like receptor 4 (TLR4) expression, however, was continuously elevated after the LPS/APAP co-exposures, which may result in reduced KC-phagocytosis and unbalanced cytokine patterns. Compared to the treatment with LPS only, LPS/APAP co-exposures induced the production of interleukin (IL)-8, a pro-inflammatory cytokine, but suppressed the secretion of IL-6, a cytokine regulating hepatic regeneration, along with the increase in APAP dosages. In addition to the disrupted mitochondrial functions, the presence of LPS exacerbated APAP toxicity. These findings suggest that 3D Microtissues are a suitable model for the mechanistic exploration of inflammation-associated drug toxicity.


Assuntos
Citocinas/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Técnicas de Cultura de Tecidos/métodos , Acetaminofen/toxicidade , Analgésicos não Entorpecentes/toxicidade , Técnicas de Cocultura , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Humanos , Macrófagos do Fígado/efeitos dos fármacos , Receptores de IgG/genética , Receptores de IgG/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Transcriptoma/efeitos dos fármacos
8.
Environ Toxicol Pharmacol ; 69: 137-142, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31071662

RESUMO

Synthetic sex steroids, like the synthetic progestin norethindrone (NET), can affect a wide variety of biological processes via highly conserved mechanisms. NET is prevalent in surface waters, yet the sub-lethal effects of NET exposure are not are net yet well characterized in aquatic biota. A few targeted gene expression and behavioral studies have concluded that NET affects the vision of adult fish; however, early life stage (ELS) fish are often more sensitive to contaminants. Furthermore, many species of fish rely heavily on visual perception for survival during development. The goal of the present study was to characterize the effects of developmental exposure to environmentally relevant concentrations of NET on the visual system of ELS zebrafish, using transcriptomics and histological methods. Results indicate that exposure to relatively low levels of NET in aquatic systems may be sufficient to affect the visual function of developing fish.


Assuntos
Anticoncepcionais Orais Sintéticos/toxicidade , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Noretindrona/toxicidade , Transcriptoma/efeitos dos fármacos , Visão Ocular/genética , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/genética , Animais , Embrião não Mamífero/efeitos dos fármacos , Olho/anatomia & histologia , Olho/efeitos dos fármacos
9.
Aquat Toxicol ; 212: 222-232, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31136897

RESUMO

Microcystin-LR (MC-LR) is a highly toxic hepatotoxin that poses great hazards to aquatic organisms and even human health. The zebrafish liver cell line (ZFL) is a valuable model for investigating toxicity and metabolism of toxicants. However, the toxicity of MC-LR and its effects on gene transcription of ZFL cells remains to be characterized. In this study, we determined the toxicity of MC-LR for ZFL cells and investigated the effects of MC-LR on cellular transcriptome dynamics. The EC50 of MC-LR for ZFL cells was 80.123 µg/mL. The ZFL cells were exposed to 10 µg/mL MC-LR for 0, 1, 3, 6, 12 or 24 h, and RNA-sequencing was performed to analyze gene transcription. A total of 10,209 genes were found to be regulated by MC-LR. The numbers of up- and down-regulated genes at different time points ranged from 2179 to 3202 and from 1501 to 2597, respectively. Furthermore, 1543 genes underwent differential splicing (AS) upon MC-LR exposure, of which 620 were not identified as differentially expressed gene (DEG). The effects of MC-LR on cellular functions were highly time-dependent. MAPK (mitogen-activated protein kinase) and FoxO (forkhead box O) signaling pathways were the most prominent pathways activated by MC-LR. Steroid biosynthesis and terpenoid backbone biosynthesis were the most enriched for the down-regulated genes. A gene regulatory network was constructed from the expression profile datasets and the candidate master transcription factors were identified. Our results shed light on the molecular mechanisms of MC-LR cellular toxicity and the transcriptome landscapes of ZFL cells upon MC-LR toxicity.


Assuntos
Microcistinas/toxicidade , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Animais , Linhagem Celular , Regulação para Baixo/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Fígado/citologia , Fígado/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia
10.
Aquat Toxicol ; 212: 233-240, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31146055

RESUMO

Crude oil and polycyclic aromatic hydrocarbon (PAH) exposure in early life stage fish has been well-characterized to induce phenotypic malformations such as altered heart development and other morphological impacts. The effects of chemical oil dispersants on toxicity are more controversial. To better understand how chemical dispersion of oil can impact toxicity in pelagic fish, embryos of mahi-mahi (Coryphaena hippurus) were exposed to three concentrations of the chemical dispersant Corexit 9500A, or Corexit 9500A-oil mixtures (chemically enhanced water accommodated fractions: CEWAF) of Deepwater Horizon crude oil for 48 h. RNA sequencing, gene ontology enrichment, and phenotypic measurements were conducted to assess toxicity. Exposure to Corexit 9500A altered expression of less than 50 genes at all concentrations (2.5, 5, and 10 mg/L nominal concentration) and did not induce acute mortality or phenotypic malformations, corroborating other studies showing minimal effects of Corexit 9500A on developing mahi-mahi embryos. CEWAF preparations contained environmentally relevant ∑PAH concentrations ranging from 1.4 to 3.1 µg/L and similarly did not alter larval morphology. Differentially expressed genes and significantly altered pathways related to cardiotoxicity, visual impairments, and Ca2+ homeostasis reinforced previous work that expression of genes associated with the heart and eye are highly sensitive molecular endpoints in oil-exposed early life stage fish. Differential expression and gene ontology pathways were similar across the three CEWAF treatments, indicating that increased chemical dispersion did not alter molecular outcomes within the range tested here. In addition, significant sublethal molecular responses occurred in the absence of observable phenotypic changes to the heart, indicating that effects of oil on early life stage fish may not be completely dependent on cardiac function.


Assuntos
Lipídeos/toxicidade , Perciformes/fisiologia , Petróleo/toxicidade , Transcriptoma/efeitos dos fármacos , Animais , Desenvolvimento Embrionário/efeitos dos fármacos , Coração/efeitos dos fármacos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Poluentes Químicos da Água/toxicidade
11.
BMC Plant Biol ; 19(1): 213, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31117942

RESUMO

BACKGROUND: Atriplex canescens is a typical C4 secretohalophyte with salt bladders on the leaves. Accumulating excessive Na+ in tissues and salt bladders, maintaining intracellular K+ homeostasis and increasing leaf organic solutes are crucial for A. canescens survival in harsh saline environments, and enhanced photosynthetic activity and water balance promote its adaptation to salt. However, the molecular basis for these physiological mechanisms is poorly understood. Four-week-old A. canescens seedlings were treated with 100 mM NaCl for 6 and 24 h, and differentially expressed genes in leaves and roots were identified, respectively, with Illumina sequencing. RESULTS: In A. canescens treated with 100 mM NaCl, the transcripts of genes encoding transporters/channels for important nutrient elements, which affect growth under salinity, significantly increased, and genes involved in exclusion, uptake and vacuolar compartmentalization of Na+ in leaves might play vital roles in Na+ accumulation in salt bladders. Moreover, NaCl treatment upregulated the transcripts of key genes related to leaf organic osmolytes synthesis, which are conducive to osmotic adjustment. Correspondingly, aquaporin-encoding genes in leaves showed increased transcripts under NaCl treatment, which might facilitate water balance maintenance of A. canescens seedlings in a low water potential condition. Additionally, the transcripts of many genes involved in photosynthetic electron transport and the C4 pathway was rapidly induced, while other genes related to chlorophyll biosynthesis, electron transport and C3 carbon fixation were later upregulated by 100 mM NaCl. CONCLUSIONS: We identified many important candidate genes involved in the primary physiological mechanisms of A. canescens salt tolerance. This study provides excellent gene resources for genetic improvement of salt tolerance of important crops and forages.


Assuntos
Atriplex/fisiologia , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Tolerância ao Sal/genética , Plantas Tolerantes a Sal/fisiologia , Transcriptoma , Atriplex/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas/fisiologia , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Plantas Tolerantes a Sal/genética , Transcriptoma/efeitos dos fármacos
12.
Environ Pollut ; 251: 22-29, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31071629

RESUMO

This study evaluated hormetic effect of oxidative stress exerted by fullerene crystals (nC60) on Daphnia pulex, employing transcriptomics and metabolomics. D. pulex were exposed to various concentrations of nC60 for 21 days. Hormetic effect of oxidative stress was most evident after 7 days, with markedly increased L-Glutathione (GSH) concentration and Superoxide Dismutase (SOD) activity at low doses of nC60 exposure, and oppositely at high doses. The transcriptomics and metabolomics were used to elucidate the molecular mechanism underlying the hormesis in oxidative stress. There were significant alterations in major pathways involving oxidative stress and energy metabolism in D. pulex. Some important intermediates and the expression of their regulatory genes coincided with each other with first up-regulated and then down-regulated with the concentration increased, consistent with the hormesis description. The nC60 interfered the TCA cycle of D. pulex. The synthesis of L-cysteine and glutamate was directly affected, and further disturbed the synthesis of GSH. This work is of great significance to provide the molecular-level evidence into the hormetic effect in oxidative stress of D. pulex exposed to nC60.


Assuntos
Daphnia/efeitos dos fármacos , Fulerenos/toxicidade , Hormese/efeitos dos fármacos , Nanopartículas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Daphnia/genética , Daphnia/metabolismo , Perfilação da Expressão Gênica , Glutationa/metabolismo , Metabolômica , Transcriptoma/efeitos dos fármacos
13.
Chemosphere ; 230: 628-639, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31128509

RESUMO

The current study evaluated the synergistic role of Plant growth promoting rhizobacteria (PGPR), Pseudomonas aeruginosa and Burkholderia gladioli on different physiological, biochemical and molecular activities of 10-days old Solanum lycopersicum seedlings under Cd stress. Cd toxicity altered the levels of phenolic compounds (total phenols (30.2%), flavonoids (92.7%), anthocyanin (59.5%), polyphenols (368.7%)), osmolytes (total osmolytes (10.3%), total carbohydrates (94%), reducing sugars (64.5%), trehalose (112.5%), glycine betaine (59%), proline (54.8%), and free amino acids (63%)), and organic acids in S. lycopersicum seedlings. Inoculation of P. aeruginosa and B. gladioli alleviated Cd-induced toxicity, which was manifested through enhanced phenolic compound levels and osmolytes. Additionally, the levels of low molecular weight organic acids (fumaric acid, malic acid, succinic acid, and citric acid) were also elevated. The expression of genes encoding enzymes for phenols and organic acid metabolism were also studied to be modulated that included CHS (chalcone synthase; 138.4%), PAL (phenylalanine ammonia lyase; 206.7%), CS (citrate synthase; 61.3%), SUCLG1 (succinyl Co-A ligase; 33.6%), SDH (succinate dehydrogenase; 23.2%), FH (fumarate hydratase; 12.4%), and MS (malate synthase; 41.2%) and found to be upregulated in seedlings inoculated independently with P. aeruginosa and B. gladioli. The results provide insights into the role of micro-organisms in alleviating Cd-induced physiological damage by altering levels of different metabolites.


Assuntos
Burkholderia gladioli/crescimento & desenvolvimento , Cádmio/toxicidade , Lycopersicon esculentum/metabolismo , Polifenóis/metabolismo , Pseudomonas aeruginosa/crescimento & desenvolvimento , Poluentes do Solo/toxicidade , Perfilação da Expressão Gênica , Genes de Plantas , Lycopersicon esculentum/efeitos dos fármacos , Lycopersicon esculentum/genética , Lycopersicon esculentum/microbiologia , Desenvolvimento Vegetal/efeitos dos fármacos , Desenvolvimento Vegetal/genética , Rizosfera , Transcriptoma/efeitos dos fármacos
14.
Environ Sci Pollut Res Int ; 26(17): 17834-17844, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31037530

RESUMO

Selenium (Se) is a vital element which leads to strong antioxidation in animals and humans. However, the mechanism underlying natural cereal Se-induced biological changes is not well understood. This study intended to explore the gene differential expression in naturally aged mice exposed to selenium by RNA-Seq technique. A total spectrum of 53 differentially expressed genes was quantified in mice heart tissues treated with Se-rich and general rice. The GO functional annotation of differentially expressed genes disclosed the enrichment of cellular process, ionic binding, biological regulation, and catalytic activity. One hundred twenty-three differential pathways (cardiovascular diseases, immune system, transport and catabolism, longevity regulating, and PI3K-AKT signaling) were identified according to KEGG metabolic terms. Afterwards, the effect of Se-rich rice on the antioxidant activity was assessed. The selenium-rich diet increased the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in mice serum and livers while significantly reduces methane dicarboxylic aldehyde (MDA) contents. FOXO1 and FOXO3 genes, which acted as the regulators of apoptosis and the antioxidant enzyme, were significantly enhanced in mice when fed with Se-rich rice. In short, the present findings disclosed the alluring insights of organic and inorganic selenium sources on certain biological processes and antioxidant activity of living bodies. However, long-term trials are still required to draw a definitive conclusion, including risks and benefit analysis for various management strategies.


Assuntos
Antioxidantes/metabolismo , Oryza/metabolismo , Selênio/metabolismo , Animais , Glutationa Peroxidase/metabolismo , Fígado/metabolismo , Camundongos , Oryza/química , Fosfatidilinositol 3-Quinases/metabolismo , Selênio/análise , Superóxido Dismutase/metabolismo , Transcriptoma/efeitos dos fármacos
15.
Chemosphere ; 230: 432-439, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31121507

RESUMO

This study was conducted to investigate the effects of maternal exposure to BPA on testicular development in offspring males. Pregnant Kunming mice were randomly divided into 7 groups with 20 mice in each group. Group A was the control group and the mice were given distilled water orally. Mice in groups B, C, D, E, F, G received BPA orally at a dose of 0.05 mg/kg/d, 0.5 mg/kg/d, 5 mg/kg/d, 10 mg/kg/d, 20 mg/kg/d, 50 mg/kg/d, respectively. F0 mice were exposed to BPA for 40 days from gestation day 0 to lactation day 21. F1 male mice were sacrificed at weaning (postnatal day 21). Histological observations revealed architectural damages in testis in BPA exposed groups. The testicular organ index increased significantly when the BPA oral exposure dose was above 20 mg/kg/d (P < 0.05). BPA contents in serum of F1 male mice increased significantly when BPA was above 5 mg/kg/d (P < 0.05), while the contents significant increased in maternal serum when BPA was higher than 0.5 mg/kg/d. The damage of cell nuclear DNA of testis was significantly aggravated when BPA was above 5 mg/kg/d. The expression of AR in the testis was significantly increased when BPA was above 20 mg/kg/d (P < 0.05). Transcriptome sequencing showed that the Snrnp 40 which encoding U5 snRNA subunit was significantly up-regulated in spliceosome pathway, and the Hnrnpu which encoding splicing universal protein component was significantly down-regulated. The blockage of spliceosome might be one of the reasons why BPA affects testicular development.


Assuntos
Compostos Benzidrílicos/toxicidade , Poluentes Ambientais/toxicidade , Exposição Materna/efeitos adversos , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Processamento de RNA/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Feminino , Perfilação da Expressão Gênica , Lactação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Testículo/embriologia , Testículo/crescimento & desenvolvimento , Testículo/metabolismo , Transcriptoma/efeitos dos fármacos
16.
Ecotoxicol Environ Saf ; 180: 491-500, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31121556

RESUMO

Ammonia, one of the major limiting environment factors in aquaculture, may pose a threat to the shrimp growth, reproduction and survival. In this study, to understand molecular differences of transcriptomic and metabolomic responses and investigate the tolerance mechanisms underlying ammonia stress in Litopenaeus vannamei, ammonia-tolerant family (LV-AT) and ammonia-sensitive family (LV-AS) of these two extreme families were exposed to high-concentration (NH4Cl, 46 mg/L) ammonia for 24 h. The comparative transcriptome analysis between ammonia-treated and control (LV-C) groups revealed involvement of immune defense, cytoskeleton remodeling, antioxidative system and metabolic pathway in ammonia-stress response of L. vannamei. Likewise, metabolomics analysis showed that ammonia exposure could disturb amino acid metabolism, nucleotide metabolism and lipid metabolism, with metabolism related-genes changed according to RNA-seq analysis. The comparison of metabolite and transcript profiles between LV-AT and LV-AS indicated that LV-AT used the enhanced glycolysis and tricarboxylic acid (TCA) cycle strategies for energy supply and ammonia excretion to adapt high-concentration ammonia. Furthermore, some of genes involved in the detoxification and ammonia excretion were highly expressed in LV-AT. We speculate that the higher ability of ammonia excretion and detoxification and the accelerated energy metabolism for energy supplies might be the adaptive strategies for LV-AT relative to LV-AS after ammonia stress. Collectively, the combination of transcriptomics and metabolomics results will greatly contribute to incrementally understand the stress responses on ammonia exposure to L. vannamei and supply molecular level support for evaluating the environmental effects of ammonia on aquatic organisms. The results further constitute new sights on the potential molecular mechanisms of ammonia adaptive strategies in shrimps at the transcriptomics and metabolomics levels.


Assuntos
Amônia/toxicidade , Metabolismo Energético/efeitos dos fármacos , Penaeidae/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Tolerância a Medicamentos , Perfilação da Expressão Gênica , Metabolômica , Penaeidae/genética , Penaeidae/metabolismo
17.
Carbohydr Polym ; 216: 97-106, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047086

RESUMO

Here, we identified inulin-type oligosaccharides with 3-13 degrees of polymerization from Morinda officinalis. Radical-scavenging assays showed that Inulins 4-7 had modest anti-oxidative effects. Inulins 4 and 5 dose-dependently increased human umbilical vein endothelial cell survival during hypoxia/re-oxygenation (H/R)-induced injury, and Inulin 5 promoted angiogenesis. Triplicate assays with the Affymetrix Human Transcriptome Array 2.0 showed that Inulin 5 exposure up-regulated genes associated with cell cycle progression, apoptosis, DNA replication and repair, ubiquitin-mediated proteolysis, the mitogen-activated protein kinase pathway, and the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-signaling pathway. Flow cytometry, reverse transcription-quantitative polymerase chain reaction, and western blot experiments verified the microarray results and demonstrated that Inulin 5 influenced cell cycle progression and the PI3K-protein kinase B (PKB)-endothelial nitric oxide synthase (eNOS) pathway. Thus, inulin-type oligosaccharides from M. officinalis roots may protect against H/R-induced injury, primarily through an anti-oxidative effect, and promote angiogenesis by activating the PI3K-PKB-eNOS-signaling pathway.


Assuntos
Depuradores de Radicais Livres/farmacologia , Hipóxia/tratamento farmacológico , Inulina/farmacologia , Morinda/química , Oligossacarídeos/farmacologia , Indutores da Angiogênese/isolamento & purificação , Indutores da Angiogênese/farmacologia , Sequência de Carboidratos , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Depuradores de Radicais Livres/isolamento & purificação , Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Inulina/isolamento & purificação , Peso Molecular , Óxido Nítrico Sintase Tipo III/metabolismo , Oligossacarídeos/isolamento & purificação , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos
18.
BMC Res Notes ; 12(1): 250, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053168

RESUMO

OBJECTIVE: The objective of this experiment was to identify transcripts in baker's yeast (Saccharomyces cerevisiae) that could have originated from previously non-coding genomic regions, or de novo. We generated this data to be able to compare the transcriptomes of different species of Ascomycota. DATA DESCRIPTION: We generated high-depth RNA sequencing data for 11 species of yeast: Saccharomyces cerevisiae, Saccharomyces paradoxus, Saccharomyces mikatae, Saccharomyces kudriavzevii, Saccharomyces bayanus, Naumovia castelii, Kluyveromyces lactis, Lachancea waltii, Lachancea thermotolerans, Lachancea kluyveri, and Schizosaccharomyces pombe. Using RNA-Seq from yeast grown in rich and oxidative conditions we created genome-guided de novo assemblies of the transcriptomes for each species. We included synthetic spike-in transcripts in each sample to determine the lower limit of detection of the sequencing platform as well as the reliability of our de novo transcriptome assembly pipeline. We subsequently compared the de novo transcripts assemblies to the reference gene annotations and generated assemblies that comprised both annotated and novel transcripts.


Assuntos
Meios de Cultura/farmacologia , Estresse Oxidativo/genética , Transcriptoma/genética , Leveduras/crescimento & desenvolvimento , Leveduras/genética , Estresse Oxidativo/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Leveduras/efeitos dos fármacos
19.
BMC Genomics ; 20(1): 390, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31109305

RESUMO

BACKGROUND: Phytohormones are key regulators of plant growth, development, and signalling networks involved in responses to diverse biotic and abiotic stresses. Transcriptional reference maps of hormone responses have been reported for several model plant species such as Arabidopsis thaliana, Oryza sativa, and Brachypodium distachyon. However, because of species differences and the complexity of the wheat genome, these transcriptome data are not appropriate reference material for wheat studies. RESULTS: We comprehensively analysed the transcriptomic responses in wheat spikes to seven phytohormones, including indole acetic acid (IAA), gibberellic acid (GA), abscisic acid (ABA), ethylene (ET), cytokinin (CK), salicylic acid (SA), and methyl jasmonic acid (MeJA). A total of 3386 genes were differentially expressed at 24 h after the hormone treatments. Furthermore, 22.7% of these genes exhibited overlapping transcriptional responses for at least two hormones, implying there is crosstalk among phytohormones. We subsequently identified genes with expression levels that were significantly and differentially induced by a specific phytohormone (i.e., hormone-specific responses). The data for these hormone-responsive genes were then compared with the transcriptome data for wheat spikes exposed to biotic (Fusarium head blight) and abiotic (water deficit) stresses. CONCLUSION: Our data were used to develop a transcriptional reference map of hormone responses in wheat spikes.


Assuntos
Reguladores de Crescimento de Planta/farmacologia , Transcriptoma , Triticum/genética , Desidratação/genética , Desidratação/metabolismo , Flores/efeitos dos fármacos , Flores/genética , Flores/metabolismo , Fusarium , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Transcriptoma/efeitos dos fármacos , Triticum/efeitos dos fármacos , Triticum/metabolismo , Triticum/microbiologia
20.
Ann Hematol ; 98(8): 1813-1826, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31098739

RESUMO

Pregnant patients with ß-thalassemia are more likely to have progressive anemia which expose them to risk of adverse pregnancy outcomes, blood transfusion, and iron overload. Results from our previous study indicated that Colla corii asini (CCA, E'jiao), a natural ingredient of traditional Chinese medicine, could significantly increase hemoglobin level of pregnant women with ß- thalassemia, but the underlying molecular mechanism was unclear. Thus, we applied high-throughput transcriptome sequencing to study the transcriptomic change before and after the CCA treatment. Twenty eligible pregnant women were recruited and randomized to either the CCA treatment group or the blank control group in a 3:1 ratio. Patients in the treatment group orally received daily 15 g CCA powder for 4 weeks. We analyzed the therapeutic effect indexes and the transcriptomic change in subjects' peripheral blood before and after treatment. We found that ß CD 41-42(-TTCT)/ßA was the main genotype of the subjects. The regulatory impact of CCA treatment became more evident among the subjects of genotype ß CD 41-42(-TTCT)/ßA. Gene ontogenesis analysis revealed that the top five molecular functions of differentially expressed genes were involved in membrane functionality and cellular structure. We further identified two consistent upregulated genes ZNF471 and THOC5 in the effective treatment group, which were engaged in Kruppel-associated box (KRAB) domain-containing zinc-finger protein pathway and THOC5 pathway, respectively. Based on our current findings, we hypothesize that the anti-anemia effect of CCA on pregnant women with ß-thalassemia might be related to translation regulation of spectrin synthesis, membrane stability, and eventually prolonged the life span of erythrocytes.


Assuntos
Gelatina/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Fármacos Hematológicos/uso terapêutico , Medicina Tradicional Chinesa/métodos , Proteínas Nucleares/genética , Proteínas Repressoras/genética , Talassemia beta/tratamento farmacológico , Administração Oral , Adulto , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Eritrócitos/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Proteínas Nucleares/agonistas , Proteínas Nucleares/metabolismo , Gravidez , Proteômica/métodos , Proteínas Repressoras/agonistas , Proteínas Repressoras/metabolismo , Transdução de Sinais , Espectrina/genética , Espectrina/metabolismo , Transcriptoma/efeitos dos fármacos , Talassemia beta/genética , Talassemia beta/metabolismo , Talassemia beta/patologia
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