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1.
Genes (Basel) ; 12(11)2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34828340

RESUMO

Excessive aluminum ions (Al3+) in acidic soil can have a toxic effect on watermelons, restricting plant growth and reducing yield and quality. In this study, we found that exogenous application of nitric oxide (NO) could increase the photochemical efficiency of watermelon leaves under aluminum stress by promoting closure of leaf stomata, reducing malondialdehyde and superoxide anion in leaves, and increasing POD and CAT activity. These findings showed that the exogenous application of NO improved the ability of watermelon to withstand aluminum stress. To further reveal the mitigation mechanism of NO on watermelons under aluminum stress, the differences following different types of treatments-normal growth, Al, and Al + NO-were shown using de novo sequencing of transcriptomes. In total, 511 differentially expressed genes (DEGs) were identified between the Al + NO and Al treatment groups. Significantly enriched biological processes included nitrogen metabolism, phenylpropane metabolism, and photosynthesis. We selected 23 genes related to antioxidant enzymes and phenylpropane metabolism for qRT-PCR validation. The results showed that after exogenous application of NO, the expression of genes encoding POD and CAT increased, consistent with the results of the physiological indicators. The expression patterns of genes involved in phenylpropanoid metabolism were consistent with the transcriptome expression abundance. These results indicate that aluminum stress was involved in the inhibition of the photosynthetic pathway, and NO could activate the antioxidant enzyme defense system and phenylpropane metabolism to protect cells and scavenge reactive oxygen species. This study improves our current understanding by comprehensively analyzing the molecular mechanisms underlying NO-induced aluminum stress alleviation in watermelons.


Assuntos
Alumínio/metabolismo , Alumínio/toxicidade , Citrullus/efeitos dos fármacos , Citrullus/fisiologia , Óxido Nítrico/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Transcriptoma , Fenômenos Biológicos/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Nitrogênio/metabolismo , Fotossíntese/efeitos dos fármacos , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Propanóis/metabolismo , Solo/química
2.
Cell Prolif ; 54(10): e13119, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34435400

RESUMO

OBJECTIVES: Histone deacetylase 8 (HDAC8) is one of the class I HDAC family proteins, which participates in the neuronal disorders, parasitic/viral infections, tumorigenesis and many other biological processes. However, its potential function during female germ cell development has not yet been fully understood. MATERIALS AND METHODS: HDAC8-targeting siRNA was microinjected into GV oocytes to deplete HDAC8. PCI-34051 was used to inhibit the enzyme activity of HDAC8. Immunostaining, immunoblotting and fluorescence intensity quantification were applied to assess the effects of HDAC8 depletion or inhibition on the oocyte meiotic maturation, spindle/chromosome structure, γ-tubulin dynamics and acetylation level of α-tubulin. RESULTS: We observed that HDAC8 was localized in the nucleus at GV stage and then translocated to the spindle apparatus from GVBD to M II stages in porcine oocytes. Depletion of HDAC8 led to the oocyte meiotic failure by showing the reduced polar body extrusion rate. In addition, depletion of HDAC8 resulted in aberrant spindle morphologies and misaligned chromosomes due to the defective recruitment of γ-tubulin to the spindle poles. Notably, these meiotic defects were photocopied by inhibition of HDAC8 activity using its specific inhibitor PCI-34051. However, inhibition of HDAC8 did not affect microtubule stability as assessed by the acetylation level of α-tubulin. CONCLUSIONS: Collectively, our findings demonstrate that HDAC8 acts as a regulator of spindle assembly during porcine oocyte meiotic maturation.


Assuntos
Histona Desacetilases/metabolismo , Meiose/fisiologia , Oócitos/metabolismo , Fuso Acromático/metabolismo , Acetilação/efeitos dos fármacos , Animais , Fenômenos Biológicos/efeitos dos fármacos , Cromossomos/efeitos dos fármacos , Cromossomos/metabolismo , Cromossomos/fisiologia , Feminino , Ácidos Hidroxâmicos/farmacologia , Indóis/farmacologia , Meiose/efeitos dos fármacos , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Microtúbulos/fisiologia , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Fuso Acromático/efeitos dos fármacos , Fuso Acromático/fisiologia , Suínos , Tubulina (Proteína)/metabolismo
3.
Life Sci ; 270: 119079, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33460668

RESUMO

Age-associated memory loss is highly prevalent in the elder population. The inception of neurodegenerative diseases acts as a causative factor for the onset of memory loss in aged individuals. The pathophysiological mechanisms of memory loss associated with the onset of neurodegenerative diseases and normal aging processes share certain similarities as well as differences. The normal age-associated memory loss is attributed to the impairment of calcium metabolism, dysregulated cholesterol metabolism, the prevalence of oxidative stress, inappropriate functioning of hormones as well as genetic factors. Vital information regarding the key biological processes and the druggable targets involved in the onset of memory loss in the elder population has been provided in this article. The genomic and proteomic profiles of key druggable targets retrieved from the experimental evidence, co-expression studies and databases are also presented in this article. The genomic and proteomic information of druggable targets will aid in the identification of therapeutic agents which could effectively regulate the key biological processes involved in the age-associated memory loss.


Assuntos
Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Envelhecimento/metabolismo , Fenômenos Biológicos/efeitos dos fármacos , Cálcio/metabolismo , Colesterol/metabolismo , Genoma , Genômica , Hormônios , Humanos , Doenças Neurodegenerativas/metabolismo , Estresse Oxidativo/fisiologia , Proteômica
4.
PLoS One ; 15(4): e0230944, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32267857

RESUMO

A new species of encyrtid wasp, Metaphycus macadamiae Polaszek & Noyes sp. n., (Hymenoptera: Encyrtidae: Encyrtinae) is described as a solitary endoparasitoid of the invasive macadamia felted coccid, Acanthococcus ironsidei (Hemiptera: Eriococcidae) in Hawaii. This parasitoid is native to Australia, and the species description is based on material collected from a Macadamia integrifolia Maiden & Betche (Proteaceae) plantation in New South Wales, Australia, the native region of the host tree and insect. It is described here because it is a potential biological control agent against this pest where it has recently invaded Hawaii and South Africa.


Assuntos
Hemípteros/efeitos dos fármacos , Macadamia/química , Animais , Austrália , Fenômenos Biológicos/efeitos dos fármacos , Havaí , Himenópteros/efeitos dos fármacos , New South Wales , Controle Biológico de Vetores/métodos , África do Sul , Vespas/efeitos dos fármacos
5.
Technol Cancer Res Treat ; 17: 1533033818809997, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30384806

RESUMO

In recent study, microRNAs have various important functions in diverse biological processes and progression of cancer. In human breast cancer, microRNA-22 has been reported to be downregulated. However, molecular mechanism of microRNA-22 in breast cancer progression and chemosensitivity has not been well studied. In our study, these results demonstrated that microRNA-22 expression levels were significantly reduced in 40 pairs of human breast cancer tissues when compared to normal tissues. Enforced expression of microRNA-22 inhibited activity of cell proliferation and cell migration in breast cancer cells. Furthermore, microRNA-22 targeted NRAS proto-oncogene, GTPase (NRAS) in breast cancer cells. The expression levels of NRAS in human clinical specimens were higher in breast cancer tissues when compared to normal tissues. Moreover, microRNA-22 sensitized breast cancer cells to paclitaxel by regulation of NRAS. Our results then demonstrated that microRNA-22 functioned as a tumor suppressor microRNA and indicated potential application for the diagnosis and treatment of cancer in the future.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Proliferação de Células/genética , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , MicroRNAs/genética , Paclitaxel/farmacologia , Fenômenos Biológicos/efeitos dos fármacos , Fenômenos Biológicos/genética , Mama/efeitos dos fármacos , Mama/patologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor/efeitos dos fármacos , Genes Supressores de Tumor/fisiologia , Células HEK293 , Humanos , Células MCF-7 , Proto-Oncogene Mas
6.
Expert Opin Biol Ther ; 18(sup1): 23-31, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30063863

RESUMO

BACKGROUND: Thymosin alpha 1 (Tα1) is a well-recognized immune response modulator in a wide range of disorders, particularly infections and cancer. The bioinformatic analysis of public databases allows drug repositioning, predicting a new potential area of clinical intervention. We aimed to decipher the cellular network induced by Tα1 treatment to confirm present use and identify new potential clinical applications. RESEARCH DESIGN AND METHODS: We used the transcriptional profile of human peripheral blood mononuclear cells treated in vitro with Tα1 to perform the enrichment network analysis by the Metascape online tools and the disease enrichment analysis by the DAVID online tool. RESULTS: Networked cellular responses reflected Tα1 regulated biological processes including immune and metabolic responses, response to compounds and oxidative stress, ion homeostasis, peroxisome biogenesis and drug metabolic process. Beyond cancer and infections, the analysis evidenced the association with disorders such as kidney chronic failure, diabetes, cardiovascular, chronic respiratory, neuropsychiatric, neurodegenerative and autoimmune diseases. CONCLUSIONS: In addition to the known ability to promote immune response pathways, the network enrichment analysis demonstrated that Tα1 regulates cellular metabolic processes and oxidative stress response. Notable, the analysis highlighted the association with several diseases, suggesting new translational implication of Tα1 treatment in pathological conditions unexpected until now.


Assuntos
Infecções/tratamento farmacológico , Leucócitos Mononucleares/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Timalfasina/uso terapêutico , Transcriptoma/efeitos dos fármacos , Doenças Autoimunes/tratamento farmacológico , Fenômenos Biológicos/efeitos dos fármacos , Fenômenos Biológicos/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Infecções/sangue , Infecções/genética , Leucócitos Mononucleares/metabolismo , Análise em Microsséries , Neoplasias/sangue , Neoplasias/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
7.
Biointerphases ; 13(4): 040801, 2018 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-30049219

RESUMO

The genesis for this topical review stems from the interdisciplinary Biointerfaces International conference 2016 (BI 2016) in Zurich, Switzerland, wherein the need for advances in analytical tools was both expressed and addressed. Pushing the limits of detection for characterizing individual components, such as single proteins, single drug-delivery vehicles, or probing single living cells in a more natural environment, will contribute to the understanding of the complex biomolecular systems central to a number of applications including medical diagnostics, tissue engineering, and drug screening and delivery. Accordingly, the authors begin with an overview of single nanoparticle analytics highlighting two emerging techniques and how they compare with existing techniques. The first is based on single particle tracking of nanoparticles tethered to a mobile supported lipid bilayer, enabling the simultaneous characterization of both size and composition of individual nanoparticles. The second technique is based on probing variations in the ionic conduction across nanoscale apertures for detection of not only nanoparticles but also membrane-tethered proteins, thereby allowing a multiparameter characterization of individual nanoscopic objects, addressing their size, shape, charge, and dipole moment. Subsequently, the authors lead into an example of an area of application that stands to benefit from such advances in bioanalytics, namely, the development of biomimetic lipid- and polymer-based assemblies as stimuli-responsive artificial organelles and nanocarriers designed to optimize delivery of next generation high-molecular-weight biological drugs. This in turn motivates the need for additional advanced techniques for investigating the cellular response to drug delivery, and so the review returns again to bioanalytics, in this case single-cell analysis, while highlighting a technique capable of probing and manipulating the content of individual living cells via fluidic force microscopy. In presenting a concerted movement in the field of bioinspired bioanalytics, positioned in the context of drug delivery, while also noting the critical role of surface modifications, it is the authors' aim to evaluate progress in the field of single component bioanalytics and to emphasize the impact of initiating and maintaining a fruitful dialogue among scientists, together with clinicians and industry, to guide future directions in this area and to steer innovation to successful translation.


Assuntos
Fenômenos Biológicos/efeitos dos fármacos , Técnicas Citológicas/métodos , Nanotecnologia/métodos , Técnicas Citológicas/tendências , Nanotecnologia/tendências
8.
Chem Soc Rev ; 47(4): 1189-1249, 2018 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-29296992

RESUMO

A systematic analysis of all synthetic and chemoenzymatic methodologies for the preparation of aminoglycosides for a variety of applications (therapeutic and agricultural) reported in the scientific literature up to 2017 is presented. This comprehensive analysis of derivatization/generation of novel aminoglycosides and their conjugates is divided based on the types of modifications used to make the new derivatives. Both the chemical strategies utilized and the biological results observed are covered. Structure-activity relationships based on different synthetic modifications along with their implications for activity and ability to avoid resistance against different microorganisms are also presented.


Assuntos
Aminoglicosídeos/química , Aminoglicosídeos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Fenômenos Biológicos/efeitos dos fármacos , Animais , Técnicas de Química Sintética/métodos , Humanos , Estrutura Molecular , Polissacarídeos/química , Relação Estrutura-Atividade
9.
Sci Rep ; 8(1): 958, 2018 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-29343839

RESUMO

Music can improve the efficiency of medical treatment when correctly associated with drug action, reducing risk factors involving deteriorating cardiac function. We evaluated the effect of musical auditory stimulus associated with anti-hypertensive medication on heart rate (HR) autonomic control in hypertensive subjects. We evaluated 37 well-controlled hypertensive patients designated for anti-hypertensive medication. Heart rate variability (HRV) was calculated from the HR monitor recordings of two different, randomly sorted protocols (control and music) on two separate days. Patients were examined in a resting condition 10 minutes before medication and 20 minutes, 40 minutes and 60 minutes after oral medication. Music was played throughout the 60 minutes after medication with the same intensity for all subjects in the music protocol. We noted analogous response of systolic and diastolic arterial pressure in both protocols. HR decreased 60 minutes after medication in the music protocol while it remained unchanged in the control protocol. The effects of anti-hypertensive medication on SDNN (Standard deviation of all normal RR intervals), LF (low frequency, nu), HF (high frequency, nu) and alpha-1 scale were more intense in the music protocol. In conclusion, musical auditory stimulus increased HR autonomic responses to anti-hypertensive medication in well-controlled hypertensive subjects.


Assuntos
Anti-Hipertensivos/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/psicologia , Música/psicologia , Estimulação Acústica/métodos , Sistema Nervoso Autônomo/efeitos dos fármacos , Fenômenos Biológicos/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Descanso/fisiologia , Descanso/psicologia , Fatores de Risco , Sístole/efeitos dos fármacos
10.
Biochim Biophys Acta Gen Subj ; 1861(5 Pt A): 1190-1199, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28286014

RESUMO

BACKGROUND: We have demonstrated that intramyocardial delivery of human mesenchymal stem cells preconditioned with a hyaluronan mixed ester of butyric and retinoic acid (MSCp+) is more effective in preventing the decay of regional myocardial contractility in a swine model of myocardial infarction (MI). However, the understanding of the role of MSCp+ in proteomic remodeling of cardiac infarcted tissue is not complete. We therefore sought to perform a comprehensive analysis of the proteome of infarct remote (RZ) and border zone (BZ) of pigs treated with MSCp+ or unconditioned stem cells. METHODS: Heart tissues were analyzed by MudPIT and differentially expressed proteins were selected by a label-free approach based on spectral counting. Protein profiles were evaluated by using PPI networks and their topological analysis. RESULTS: The proteomic remodeling was largely prevented in MSCp+ group. Extracellular proteins involved in fibrosis were down-regulated, while energetic pathways were globally up-regulated. Cardioprotectant pathways involved in the production of keto acid metabolites were also activated. Additionally, we found that new hub proteins support the cardioprotective phenotype characterizing the left ventricular BZ treated with MSCp+. In fact, the up-regulation of angiogenic proteins NCL and RAC1 can be explained by the increase of capillary density induced by MSCp+. CONCLUSIONS: Our results show that angiogenic pathways appear to be uniquely positioned to integrate signaling with energetic pathways involving cardiac repair. GENERAL SIGNIFICANCE: Our findings prompt the use of proteomics-based network analysis to optimize new approaches preventing the post-ischemic proteomic remodeling that may underlie the limited self-repair ability of adult heart.


Assuntos
Fenômenos Biológicos/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Regulação para Baixo/efeitos dos fármacos , Fibrose/metabolismo , Humanos , Cetoácidos/metabolismo , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Neovascularização Patológica/metabolismo , Proteômica/métodos , Suínos , Tretinoína/farmacologia , Regulação para Cima/efeitos dos fármacos
11.
J Anesth ; 29(6): 912-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26223573

RESUMO

OBJECTIVE: To identify differentially expressed genes (DEGs) and further analyze potential biological processes and pathways involved in isoflurane-induced anesthesia. METHODS: Microarray data (ID: GSE64617) from rat brains treated with exposure to either isoflurane in oxygen (2%) (test group) or oxygen alone (control group) for 15 min were downloaded from Gene Expression Omnibus. Data pre-processing was performed using the Affy package, followed by DEG screening using the limma package. Protein-protein interactions (PPIs) among DEGs were obtained from STRING (Search Tool for the Retrieval of Interacting Genes/Proteins), and then visualized by constructing a network using Cytoscape. Functional and pathway enrichment analyses were further implemented to identify the biological processes and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways enriched by DEGs. RESULTS: A total of 240 DEGs were identified between the test and control groups, including 128 up-regulated DEGs and 112 down-regulated DEGs in the test group, of which 17 DEGs with a connectivity degree >4 were identified as hub genes (e.g., Pik3r1 and Pik3r2) in the constructed PPI network. Additionally, Slc17a7 and Camk4 interacted with Syn1, and Pik3r1 interacted with Pik3r2. Enrichment analysis further revealed the significantly enriched biological processes of 'synaptic transmission', 'cell-cell signaling' and 'transmission of nerve impulse' (e.g., Slc17a7, Camk4, Syn1, Gria1, Prkcg and Lphn1), as well as KEGG pathways including 'focal adhesion', 'Fc γ R-mediated phagocytosis' (e.g., Prkcg, Pik3r1 and Pik3r2), and 'regulation of actin cytoskeleton' (e.g., Pik3r1 and Pik3r2). CONCLUSIONS: The identified DEGs significantly enriched in biological processes and KEGG pathways might be implicated in isoflurane-induced anesthesia.


Assuntos
Biologia Computacional , Regulação para Baixo/efeitos dos fármacos , Isoflurano/farmacologia , Regulação para Cima/efeitos dos fármacos , Anestesia/métodos , Animais , Fenômenos Biológicos/efeitos dos fármacos , Perfilação da Expressão Gênica , Masculino , Ratos , Transdução de Sinais
12.
J Toxicol Sci ; 40(1): 55-69, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25743563

RESUMO

Inorganic phosphate (Pi) plays crucial roles in several biological processes and signaling pathways. Pi uptake is regulated by sodium-dependent phosphate (Na/Pi) transporters (NPTs). Moreover, Pi is used as a food additive in food items such as sausages, crackers, dairy products, and beverages. However, the high serum concentration of phosphate (> 5.5 mg/dL) can cause adverse renal effects, cardiovascular effects including vascular or valvular calcification, and stimulate bone resorption. In addition, Pi can also alter vital cellular signaling, related to cell growth and cap-dependent protein translation. Moreover, intake of dietary Pi, whether high (1.0%) or low (0.1%), affects organs in developing mice, and is related to tumorigenesis in mice. The recommended dietary allowance (RDA) of Pi is the daily dietary intake required to maintain levels above the lower limit of the range of normal serum Pi concentration (2.7 mg/dL) for most individuals (97-98%). Thus, adequate intake of Pi (RDA; 700 mg/day) and maintenance of normal Pi concentration (2.7-4.5 mg/dL) are important for health and prevention of diseases caused by inadequate Pi intake.


Assuntos
Fenômenos Biológicos , Aditivos Alimentares , Fosfatos/efeitos adversos , Fosfatos/toxicidade , Transdução de Sinais , Animais , Fenômenos Biológicos/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Camundongos , Proteínas de Transporte de Fosfato/fisiologia , Fosfatos/metabolismo , Fosfatos/fisiologia , Recomendações Nutricionais , Transdução de Sinais/efeitos dos fármacos , Sódio/fisiologia
13.
BMC Syst Biol ; 8: 55, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24886091

RESUMO

BACKGROUND: The TGF-ß signaling pathway is a fundamental pathway in the living cell, which plays a key role in many central cellular processes. The complex and sometimes contradicting mechanisms by which TGF-ß yields phenotypic effects are not yet completely understood. In this study we investigated and compared the transcriptional response profile of TGF-ß1 stimulation in different cell types. For this purpose, extensive experiments are performed and time-course microarray data are generated in human and mouse parenchymal liver cells, human mesenchymal stromal cells and mouse hematopoietic progenitor cells at different time points. We applied a panel of bioinformatics methods on our data to uncover common patterns in the dynamic gene expression response in respective cells. RESULTS: Our analysis revealed a quite variable and multifaceted transcriptional response profile of TGF-ß1 stimulation, which goes far beyond the well-characterized classical TGF-ß1 signaling pathway. Nonetheless, we could identify several commonly affected processes and signaling pathways across cell types and species. In addition our analysis suggested an important role of the transcription factor EGR1, which appeared to have a conserved influence across cell-types and species. Validation via an independent dataset on A549 lung adenocarcinoma cells largely confirmed our findings. Network analysis suggested explanations, how TGF-ß1 stimulation could lead to the observed effects. CONCLUSIONS: The analysis of dynamical transcriptional response to TGF-ß treatment experiments in different human and murine cell systems revealed commonly affected biological processes and pathways, which could be linked to TGF-ß1 via network analysis. This helps to gain insights about TGF-ß pathway activities in these cell systems and its conserved interactions between the species and tissue types.


Assuntos
Fenômenos Biológicos/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos , Fator de Crescimento Transformador beta1/farmacologia , Animais , Linhagem Celular Tumoral , Análise por Conglomerados , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Proteína 2 de Resposta de Crescimento Precoce/metabolismo , Células Hep G2 , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Especificidade de Órgãos , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
14.
Arch Oral Biol ; 59(9): 928-37, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24907522

RESUMO

OBJECTIVES: The aim of this study was to evaluate the effect of SLPI on the growth and biological processes of Candida albicans. METHODS: Two C. albicans strains were used in this study, a clinical isolate resistant to fluconazole (PRI) and a reference strain ATCC 24433. The minimal inhibitory concentration (MIC) was determined according to the CLSI methodology. The influence of SLPI on secreted serine proteinase activities (SSP) was measured by the cleavage of specific substrate, and surface hydrophobicity was determined by the aqueous-hydrocarbon biphasic separation method. Flow cytometry was performed to investigate receptors for SLPI and variations in the cell wall mannoprotein expression. Interaction between yeast and epithelium was assessed using the MA-104 cells lineage. Ultrastructure was analyzed by transmission electron microscopy (TEM). RESULTS: MIC values were calculated as 18 and 18.9µM for the PRI and ATCC 24433, respectively. SSP activity was reduced by 48.8% by 18µM of SLPI and cell surface hydrophobicity increased by 11.1%. Flow cytometry suggest the existence of SLPI binding sites on the surface of the yeast. Results showed a reduction in the expression of mannoproteins in 20.8% by the cells treated with 80µM of SLPI, and 18µM reduced the adhesion of yeasts to mammalian cells in 60.1%. TEM revealed ultrastructural changes in cells treated with 80µM of SLPI, such as the presence of membrane-like structures within the cytoplasm. CONCLUSIONS: SLPI exerts a significant influence on C. albicans viability and biological processes. Considering its constitutive and physiologic features, SLPI may become a promising tool for the development of new methodologies for the treatment and control of candidiasis.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Inibidor Secretado de Peptidases Leucocitárias/farmacologia , Fenômenos Biológicos/efeitos dos fármacos , Candida albicans/ultraestrutura , Adesão Celular/efeitos dos fármacos , Farmacorresistência Fúngica , Citometria de Fluxo , Fluconazol/farmacologia , Humanos , Técnicas In Vitro , Glicoproteínas de Membrana/metabolismo , Testes de Sensibilidade Microbiana , Microscopia Eletrônica , Nistatina/farmacologia
16.
An. bras. dermatol ; 88(6): 930-936, Nov-Dec/2013. graf
Artigo em Inglês | LILACS | ID: lil-699007

RESUMO

BACKGROUND: The sum of environmental and genetic factors affects the appearance and function of the skin as it ages. The identification of molecular changes that take place during skin aging provides biomarkers and possible targets for therapeutic intervention. Retinoic acid in different formulations has emerged as an alternative to prevent and repair age-related skin damage. OBJECTIVES: To understand the effects of different retinoid formulations on the expression of genes associated with biological processes that undergo changes during skin aging. METHODS: Ex-vivo skin samples were treated topically with different retinoid formulations. The modulation of biological processes associated with skin aging was measured by Reverse Transcription quantitative PCR (RT-qPCR). RESULTS: A formulation containing microencapsulated retinol and a blend of active ingredients prepared as a triple nanoemulsion provided the best results for the modulation of biological, process-related genes that are usually affected during skin aging. CONCLUSION: This association proved to be therapeutically more effective than tretinoin or microencapsulated retinol used singly. .


FUNDAMENTOS: A soma de fatores genéticos e ambientais afeta a aparência e a funcionalidade da pele ao longo do envelhecimento. O conhecimento a respeito das mudanças moleculares durante o envelhecimento fornece biomarcadores e possíveis alvos para intervenções terapêuticas. O ácido retinoico em diferentes formulações surgiu como uma alternativa para prevenir e reparar os danos da pele associados ao envelhecimento. OBJETIVOS: Avaliar comparativamente os efeitos de diferentes formulações contendo retinoides na expressão de genes associados a processos biológicos que são alterados com o envelhecimento da pele. MÉTODOS: Peles ex vivo foram topicamente tratadas com diferentes retinoides, micro e nanoencapsulados. A modulação dos processos biológicos associados ao envelhecimento da pele foi medida por PCR quantitativa, precedida de transcrição reversa (RT-qPCR). RESULTADOS: A formulação contendo uma mistura de princípios ativos incorporados em uma tripla nanoemulsão e retinol microencapsulado apresentou os melhores resultados de modulação de genes relacionados a processos biológicos que são normalmente alterados durante o envelhecimento da pele. CONCLUSÃO: Essa associação demonstrou uma maior eficácia terapêutica quando comparada ao uso isolado de tretinoína ou retinol microencapsulado. .


Assuntos
Humanos , Ceratolíticos/uso terapêutico , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Tretinoína/uso terapêutico , Administração Tópica , Análise de Variância , Fenômenos Biológicos/efeitos dos fármacos , Sinergismo Farmacológico , Emulsões , Expressão Gênica , Ceratolíticos/farmacologia , Nanomedicina , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Envelhecimento da Pele/genética , Tretinoína/farmacologia
17.
An Bras Dermatol ; 88(6): 930-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24474102

RESUMO

BACKGROUND: The sum of environmental and genetic factors affects the appearance and function of the skin as it ages. The identification of molecular changes that take place during skin aging provides biomarkers and possible targets for therapeutic intervention. Retinoic acid in different formulations has emerged as an alternative to prevent and repair age-related skin damage. OBJECTIVES: To understand the effects of different retinoid formulations on the expression of genes associated with biological processes that undergo changes during skin aging. METHODS: Ex-vivo skin samples were treated topically with different retinoid formulations. The modulation of biological processes associated with skin aging was measured by Reverse Transcription quantitative PCR (RT-qPCR). RESULTS: A formulation containing microencapsulated retinol and a blend of active ingredients prepared as a triple nanoemulsion provided the best results for the modulation of biological, process-related genes that are usually affected during skin aging. CONCLUSION: This association proved to be therapeutically more effective than tretinoin or microencapsulated retinol used singly.


Assuntos
Ceratolíticos/uso terapêutico , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Tretinoína/uso terapêutico , Administração Tópica , Análise de Variância , Fenômenos Biológicos/efeitos dos fármacos , Sinergismo Farmacológico , Emulsões , Expressão Gênica , Humanos , Ceratolíticos/farmacologia , Nanomedicina , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Envelhecimento da Pele/genética , Tretinoína/farmacologia
18.
PLoS One ; 7(11): e49292, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23152891

RESUMO

The regulation of cellular copper homeostasis is crucial in biology. Impairments lead to severe dysfunctions and are known to affect aging and development. Previously, a loss-of-function mutation in the gene encoding the copper-sensing and copper-regulated transcription factor GRISEA of the filamentous fungus Podospora anserina was reported to lead to cellular copper depletion and a pleiotropic phenotype with hypopigmentation of the mycelium and the ascospores, affected fertility and increased lifespan by approximately 60% when compared to the wild type. This phenotype is linked to a switch from a copper-dependent standard to an alternative respiration leading to both a reduced generation of reactive oxygen species (ROS) and of adenosine triphosphate (ATP). We performed a genome-wide comparative transcriptome analysis of a wild-type strain and the copper-depleted grisea mutant. We unambiguously assigned 9,700 sequences of the transcriptome in both strains to the more than 10,600 predicted and annotated open reading frames of the P. anserina genome indicating 90% coverage of the transcriptome. 4,752 of the transcripts differed significantly in abundance with 1,156 transcripts differing at least 3-fold. Selected genes were investigated by qRT-PCR analyses. Apart from this general characterization we analyzed the data with special emphasis on molecular pathways related to the grisea mutation taking advantage of the available complete genomic sequence of P. anserina. This analysis verified but also corrected conclusions from earlier data obtained by single gene analysis, identified new candidates of factors as part of the cellular copper homeostasis system including target genes of transcription factor GRISEA, and provides a rich reference source of quantitative data for further in detail investigations. Overall, the present study demonstrates the importance of systems biology approaches also in cases were mutations in single genes are analyzed to explain the underlying mechanisms controlling complex biological processes like aging and development.


Assuntos
Fenômenos Biológicos/genética , Cobre/farmacologia , Perfilação da Expressão Gênica , Genoma Fúngico/genética , Podospora/crescimento & desenvolvimento , Podospora/genética , Fenômenos Biológicos/efeitos dos fármacos , Cobre/metabolismo , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Genes Fúngicos/genética , Ferro/metabolismo , Podospora/citologia , Podospora/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sideróforos/metabolismo
19.
Geobiology ; 10(4): 298-310, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22353368

RESUMO

Earth system climate sensitivity (ESS) is the long-term (>10³ year) response of global surface temperature to doubled CO2 that integrates fast and slow climate feedbacks. ESS has energy policy implications because global temperatures are not expected to decline appreciably for at least 10³ year, even if anthropogenic greenhouse gas emissions drop to zero. We report provisional ESS estimates of 3 °C or higher for some of the Cretaceous and Cenozoic based on paleo-reconstructions of CO2 and temperature. These estimates are generally higher than climate sensitivities simulated from global climate models for the same ancient periods (approximately 3 °C). Climate models probably do not capture the full suite of positive climate feedbacks that amplify global temperatures during some globally warm periods, as well as other characteristic features of warm climates such as low meridional temperature gradients. These absent feedbacks may be related to clouds, trace greenhouse gases (GHGs), seasonal snow cover, and/or vegetation, especially in polar regions. Better characterization and quantification of these feedbacks is a priority given the current accumulation of atmospheric GHGs.


Assuntos
Atmosfera/química , Fenômenos Biológicos/efeitos dos fármacos , Dióxido de Carbono/análise , Planeta Terra , Ecossistema , Sedimentos Geológicos/química , Clima
20.
Aquat Toxicol ; 106-107: 25-31, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-22057252

RESUMO

We investigated how persistent competitive pressure alters toxicant sensitivity and recovery from a pesticide pulse at community level. Interacting populations of Daphnia (Daphnia magna) and Culex larvae (Culex pipiens molestus) were pulse-exposed (48 h) to the pyrethroid fenvalerate. The abundance and biomass of the populations were monitored by non-invasive image analysis. Shortly after exposure, Daphnia showed a concentration-response relationship with the toxicant with an LC50 of 0.9 µg/L. Culex larvae were slightly less sensitive with an LC50 of 1.7 µg/L. For both species, toxicant sensitivity increased with the population biomass of the respective species before exposure, which is explained by intraspecific competition. Several weeks after exposure to the highest treatment concentration of 1 µg/L, the slight differences in sensitivity between the two species were amplified to contrasting long-term effects due to interspecific competition: high interspecific competition impaired the recovery of Daphnia. Subsequently, Culex larvae profited from the slow recovery of Daphnia and showed an increased success of emergence. We conclude that, in natural systems where competition is present, such competitive processes might prolong the recovery of the community structure. Hence, natural communities might be disturbed for a longer period by toxic exposure than predicted from single-species tests alone.


Assuntos
Fenômenos Biológicos/efeitos dos fármacos , Comportamento Competitivo/efeitos dos fármacos , Culex/fisiologia , Daphnia/fisiologia , Poluentes Químicos da Água/toxicidade , Animais , Biodiversidade , Nitrilas/metabolismo , Praguicidas/toxicidade , Dinâmica Populacional , Piretrinas/metabolismo , Medição de Risco , Estresse Fisiológico
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