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1.
Int J Mol Sci ; 25(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339055

RESUMO

MicroRNAs are small regulatory molecules that control gene expression. An emerging property of muscle miRNAs is the cooperative regulation of transcriptional and epitranscriptional events controlling muscle phenotype. miR-155 has been related to muscular dystrophy and muscle cell atrophy. However, the function of miR-155 and its molecular targets in muscular dystrophies remain poorly understood. Through in silico and in vitro approaches, we identify distinct transcriptional profiles induced by miR-155-5p in muscle cells. The treated myotubes changed the expression of 359 genes (166 upregulated and 193 downregulated). We reanalyzed muscle transcriptomic data from dystrophin-deficient patients and detected overlap with gene expression patterns in miR-155-treated myotubes. Our analysis indicated that miR-155 regulates a set of transcripts, including Aldh1l, Nek2, Bub1b, Ramp3, Slc16a4, Plce1, Dync1i1, and Nr1h3. Enrichment analysis demonstrates 20 targets involved in metabolism, cell cycle regulation, muscle cell maintenance, and the immune system. Moreover, digital cytometry confirmed a significant increase in M2 macrophages, indicating miR-155's effects on immune response in dystrophic muscles. We highlight a critical miR-155 associated with disease-related pathways in skeletal muscle disorders.


Assuntos
MicroRNAs , Distrofia Muscular de Duchenne , Humanos , Músculo Esquelético/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Diferenciação Celular/genética , Distrofia Muscular de Duchenne/genética
2.
Environ Geochem Health ; 46(3): 84, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38367079

RESUMO

Heavy metals can play an important biological role as micronutrients but also as potentially toxic elements (PTEs). Understanding the natural concentrations of PTEs-Pb and Zn included-in soils allows for the identification and monitoring of contaminated areas and their role in environmental risk assessment. In this study, we aim to determine semi-total or natural and available concentrations of Pb and Zn in topsoils (0-20 cm depth) from 337 samples under native vegetation in the State of Minas Gerais, Brazil. Additionally, we sought to interpret the spatial geochemical variability using geostatistical techniques and quality reference values for these elements in soils were established. The semi-total concentrations were determined by flame and graphite furnace atomic absorption after microwave-assisted nitric acid digestion method. The available concentrations were extracted using the Mehlich-I extractor and determined by atomic absorption spectrometer. Spatial variability was modeled using semivariance estimators: Matheron's classic, Cressie and Hawkins' robust, and Cressie median estimators, the last two being less sensitive to extreme values. This allowed the construction of digital maps through kriging of semi-total Pb and Zn contents using the median estimator, as well as other soil properties by the robust estimator. The dominance of acidic pH and low CEC values reflects highly weathered low-fertility soils. Semi-total Pb contents ranged from 2.1 to 278 mg kg-1 (median: 9.35 mg kg-1) whereas semi-total Zn contents ranged from 2.7 to 495 mg kg-1 (median: 7.7 mg kg-1). The available Pb contents ranged from 0.1 to 6.92 mg kg-1 (median: 0.54 mg kg-1) whereas available Zn contents ranged from 0.1 to 78.2 mg kg-1 (median: 0.32 mg kg-1). The highest Pb and Zn concentrations were observed near Januária, in the northern part of the territory, probably on limestone rocks from the Bambuí group. Finally, the QRVs for Pb and Zn in natural soils were lower than their background values from other Brazilian region and below the prevention values suggested by Brazilian environmental regulations.


Assuntos
Metais Pesados , Poluentes do Solo , Solo/química , Brasil , Chumbo , Poluentes do Solo/análise , Monitoramento Ambiental/métodos , Metais Pesados/análise , Zinco
3.
Plant Physiol Biochem ; 207: 108324, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38183903

RESUMO

Three genes encoding mitochondrial uncoupling proteins (UCPs) have been described in Arabidopsis thaliana (UCP1 to UCP3). In plants, UCPs may act as an uncoupler or as an aspartate/glutamate exchanger. For instance, much of the data regarding UCP functionality were obtained for the UCP1 and UCP2 isoforms compared with UCP3. Here, to get a better understanding about the concerted action of UCP1 and UCP3 in planta, we investigated the transcriptome and metabolome profiles of ucp1 ucp3 double mutant plants during the vegetative phase. For that, 21-day-old mutant plants, which displayed the most evident phenotypic alterations compared to wild type (WT) plants, were employed. The double knockdown of UCP1 and UCP3, isoforms unequivocally present inside the mitochondria, promoted important transcriptional reprogramming with alterations in the expression of genes related to mitochondrial and chloroplast function as well as those responsive to abiotic stress, suggesting disturbances throughout the cell. The observed transcriptional changes were well integrated with the metabolomic data of ucp1 ucp3 plants. Alterations in metabolites related to primary and secondary metabolism, particularly enriched in the Alanine, Aspartate and Glutamate metabolism, were detected. These findings extend our knowledge of the underlying roles played by UCP3 in concert with UCP1 at the whole plant level.


Assuntos
Arabidopsis , Tecido Adiposo Marrom/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Ácido Aspártico , Glutamatos/metabolismo , Canais Iônicos/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Isoformas de Proteínas/metabolismo , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 3/metabolismo
4.
Biomedicines ; 11(5)2023 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-37239116

RESUMO

Aging causes alterations in body composition. Specifically, visceral fat mass increases with age and is associated with age-related diseases. The pathogenic potential of visceral fat accumulation has been associated with its anatomical location and metabolic activity. Visceral fat may control systemic metabolism by secreting molecules that act in distal tissues, mainly the liver, through the portal vein. Currently, little is known about age-related changes in visceral fat in humans. Aiming to identify molecular and cellular changes occurring with aging in the visceral fat of humans, we analyzed publicly available transcriptomic data of 355 omentum samples from the Genotype-Tissue Expression portal (GTEx) of 20-79-year-old males and females. We identified the functional enrichment of genes associated with aging, inferred age-related changes in visceral fat cellularity by deconvolution analysis, profiled the senescence-associated secretory phenotype of visceral adipose tissue, and predicted the connectivity of the age-induced visceral fat secretome with the liver. We demonstrate that age induces alterations in visceral fat cellularity, synchronous to changes in metabolic pathways and a shift toward a pro-inflammatory secretory phenotype. Furthermore, our approach identified candidates such as ADIPOQ-ADIPOR1/ADIPOR2, FCN2-LPR1, and TF-TFR2 to mediate visceral fat-liver crosstalk in the context of aging. These findings cast light on how alterations in visceral fat with aging contribute to liver dysfunction and age-related disease etiology.

5.
J Transl Med ; 21(1): 116, 2023 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-36774484

RESUMO

BACKGROUND: Computed tomographies (CT) are useful for identifying muscle loss in non-small lung cancer (NSCLC) cachectic patients. However, we lack consensus on the best cutoff point for pectoralis muscle loss. We aimed to characterize NSCLC patients based on muscularity, clinical data, and the transcriptional profile from the tumor microenvironment to build a cachexia classification model. METHODS: We used machine learning to generate a muscle loss prediction model, and the tumor's cellular and transcriptional profile was characterized in patients with low muscularity. First, we measured the pectoralis muscle area (PMA) of 211 treatment-naive NSCLC patients using CT available in The Cancer Imaging Archive. The cutoffs were established using machine learning algorithms (CART and Cutoff Finder) on PMA, clinical, and survival data. We evaluated the prediction model in a validation set (36 NSCLC). Tumor RNA-Seq (GSE103584) was used to profile the transcriptome and cellular composition based on digital cytometry. RESULTS: CART demonstrated that a lower PMA was associated with a high risk of death (HR = 1.99). Cutoff Finder selected PMA cutoffs separating low-muscularity (LM) patients based on the risk of death (P-value = 0.003; discovery set). The cutoff presented 84% of success in classifying low muscle mass. The high risk of LM patients was also found in the validation set. Tumor RNA-Seq revealed 90 upregulated secretory genes in LM that potentially interact with muscle cell receptors. The LM upregulated genes enriched inflammatory biological processes. Digital cytometry revealed that LM patients presented high proportions of cytotoxic and exhausted CD8+ T cells. CONCLUSIONS: Our prediction model identified cutoffs that distinguished patients with lower PMA and survival with an inflammatory and immunosuppressive TME enriched with inflammatory factors and CD8+ T cells.


Assuntos
Neoplasias Pulmonares , Microambiente Tumoral , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Tomografia Computadorizada por Raios X/métodos , Músculos Peitorais/patologia
6.
Environ Res ; 215(Pt 1): 114147, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36063907

RESUMO

Mercury (Hg) toxicity in soils depends on Hg species and other physical and chemical attributes, as selenium (Se) hotspots in soils, particularly relevant in Amazonian soils. The study of Hg species and their relations in representative locations of the Amazon rainforest biome is critical for assessing the potential risks of Hg in this environment. This work aimed to determine the concentration of total Hg and its species (Hg0, Hg22+ and Hg2+), and to correlate Hgtotal concentration with total elemental composition, magnetic susceptibility, and physicochemical attributes of Amazon soils. Nine sites in the Amazon rainforest biome, Brazil, were selected and analyzed for their chemical, physical, and mineralogical attributes. The clay fraction of the studied Amazon soils is dominated by kaolinite, goethite, hematite, gibbsite, and quartz. Mica was also found in soils from the States of Acre and Amazonas. Hgtotal ranged from 21.5 to 208 µg kg-1 (median = 104 µg kg-1), and the concentrations did not exceed the threshold value established for Brazilian soils (500 µg kg-1). The Hg2+ was notably the predominant species. Its occurrence and concentration were correlated with the landscape position and soil attributes. Hgtotal was moderately and positively correlated with TiO2, clay, and Se. The findings showed that geographic location, geological formation, and pedological differences influence the heterogeneity and distribution of Hgtotal in the studied soil classes. Thus, a detailed characterization and knowledgment of the soil classes is very important to clarify the complex behavior of this metal in the Amazon rainforest biome.


Assuntos
Mercúrio , Selênio , Poluentes do Solo , Brasil , Argila , Ecossistema , Monitoramento Ambiental , Caulim , Mercúrio/análise , Quartzo , Floresta Úmida , Selênio/análise , Solo/química , Poluentes do Solo/análise
7.
Cells ; 10(12)2021 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-34944037

RESUMO

Interleukin-6 (IL-6) is a pro-inflammatory cytokine associated with skeletal muscle wasting in cancer cachexia. The control of gene expression by microRNAs (miRNAs) in muscle wasting involves the regulation of thousands of target transcripts. However, the miRNA-target networks associated with IL6-induced muscle atrophy remain to be characterized. Here, we show that IL-6 promotes the atrophy of C2C12 myotubes and changes the expression of 20 miRNAs (5 up-regulated and 15 down-regulated). Gene Ontology analysis of predicted miRNAs targets revealed post-transcriptional regulation of genes involved in cell differentiation, apoptosis, migration, and catabolic processes. Next, we performed a meta-analysis of miRNA-published data that identified miR-497-5p, a down-regulated miRNAs induced by IL-6, also down-regulated in other muscle-wasting conditions. We used miR-497-5p mimics and inhibitors to explore the function of miR-497-5p in C2C12 myoblasts and myotubes. We found that miR-497-5p can regulate the expression of the cell cycle genes CcnD2 and CcnE1 without affecting the rate of myoblast cellular proliferation. Notably, miR-497-5p mimics induced myotube atrophy and reduced Insr expression. Treatment with miR-497-5p inhibitors did not change the diameter of the myotubes but increased the expression of its target genes Insr and Igf1r. These genes are known to regulate skeletal muscle regeneration and hypertrophy via insulin-like growth factor pathway and were up-regulated in cachectic muscle samples. Our miRNA-regulated network analysis revealed a potential role for miR-497-5p during IL6-induced muscle cell atrophy and suggests that miR-497-5p is likely involved in a compensatory mechanism of muscle atrophy in response to IL-6.


Assuntos
Interleucina-6/efeitos adversos , MicroRNAs/metabolismo , Células Musculares/metabolismo , Atrofia Muscular/genética , Animais , Caquexia/etiologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Insulina/metabolismo , Camundongos , MicroRNAs/genética , Modelos Biológicos , Células Musculares/efeitos dos fármacos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Atrofia Muscular/patologia , Neoplasias/complicações , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Reprodutibilidade dos Testes , Transdução de Sinais/efeitos dos fármacos
8.
J Clin Pediatr Dent ; 45(2): 117-122, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33951171

RESUMO

OBJECTIVE: To identify the association of occlusal disorders in patients with sickle cell disease (SCD). STUDY DESIGN: A literature review was conducted, and articles published between 2010 and 2019 were searched on Bireme and PubMed websites and in MEDLINE and LILACS databases, in English, Portuguese, and Spanish, using the keywords "malocclusion," "sickle cell disease," and "cephalometry," combined by Boolean operators AND and OR. One of the criteria for the selection of articles was the presence of adolescents in the sample. This methodology followed the PRISMA recommendations. Seventy-nine articles were found, seven of which were included in the review as they met the inclusion criteria and the study goals. RESULTS: The prevalence of malocclusion in SCD patients ranged from 62.9% to 100%, which was considered very severe in 30.1% to 80.6%. The most common occlusal changes were Angle's class II malocclusion, increased maxillary overjet, and anterior open bite. In addition, class II skeletal pattern was the most prevalent due to mandibular retrusion. CONCLUSION: Malocclusion prevalence in SCD patients is high and considered to be a risk factor, with a significant rate of very severe malocclusion when compared to healthy patients.


Assuntos
Anemia Falciforme , Má Oclusão Classe II de Angle , Má Oclusão , Mordida Aberta , Sobremordida , Adolescente , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Cefalometria , Humanos , Má Oclusão/epidemiologia
9.
Environ Sci Pollut Res Int ; 28(35): 48427-48437, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33909251

RESUMO

Potentially toxic elements (PTEs) are of great concern in steel mill wastes. Therefore, in order to use them as potential fertilizers in soil, risk assessments are needed. Three steel mill wastes were tested as possible amendments for soils at seven different doses (0, 0.5, 1, 2, 4, 8, 16 t ha-1): phosphate mud (PM), metallurgical press residue (MPR), and filter press mud (FPM) during rice cultivation in a pot experiment in a Haplic Gleisol. Analysis on rice tissues, including roots, shoots, husk, and grains, were conducted and contents of Cu, Cd, Ni, Zn, Mn, and Pb were assessed. Translocation and bioaccumulation factors were calculated for each element. In general, PTEs are more accumulated in roots and greater contents of Zn and Mn were found, while the lowest ones were found for Pb, probably due to its lack of functional roles during plants development. Higher translocation was observed for Mn, which is associated to the redox conditions of rice cultivation and the high mobility of this element under this condition. Application of steel mill wastes can increase PTE bioavailability and translocation factors, especially PM, but all of the wastes reveal a high hazard index.


Assuntos
Metais Pesados , Oryza , Poluentes do Solo , Metais Pesados/análise , Solo , Poluentes do Solo/análise , Aço
10.
Environ Sci Pollut Res Int ; 28(20): 25844-25857, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33475922

RESUMO

Zinc deficiency is widespread in cultivated soils, limiting the grain crop production and the adequate human nutrition. Several wastes from metallurgical activity can be used as Zn source, but these materials generally also have other potentially toxic elements, such as Pb, that can be highly toxic for plants and humans. This study aimed to evaluate the efficiency of five chemical extractors (water, citric acid, DTPA, Mehlich 1, and USEPA 3051A) in better correlating with the bioavailable contents of Zn and Pb in soils treated with steel mill wastes (metallurgic press residue (MPR), filter press mud (FPM), and phosphate mud (PM)). Rice plants were cultivated in pots with 4 kg of a Haplic Eutrophic Gleisol and steel mill wastes were applied in soil at increasing doses (0, 0.5, 1, 2, 4, 8, and 16 t ha-1). The availability of the potentially toxic elements Zn and Pb was assessed as total contents in rice shoots, grains, husks, and roots. The results showed that the USEPA 3051A method extracted greater contents of Zn and Pb from soil compared with other extractants. Due to their greater natural Pb and Zn contents, MPR and PM promoted higher contents of these elements in soils, respectively. Doses of PM influenced Zn contents in grains. After adding 16 t ha-1 of PM, Zn content in rice grains was 0.1 mg kg-1. However, at doses 0.5, 1, 2, and 4 t ha-1, the average concentration of Zn in the grains was 40 mg kg-1. The wastes MPR and FPM at 16 t ha-1 promoted Zn concentration in grains of 42 and 45 mg kg-1, respectively. The greatest contents of Pb in grains were found after addition of FPM at doses 0.5, 1, and 2 t ha-1: 6.67, 4.96, and 0.45 mg kg-1, respectively, and above 4 t ha-1 (4, 8, and 16 t ha-1); Pb content in grains was less than 0.3 mg kg-1. The content of Pb in roots at 16 t ha-1 of PM, MPR, and FPM was 18, 25, and 155 mg kg-1, respectively, and for Zn, under the same conditions, 100, 255, and 813 mg kg-1 for MPR, FPM, and PM, respectively. USEPA 3051A can be used to assess Pb and Zn available contents, and positive correlations with bioavailable contents of these elements in roots prove its feasibility. Further studies are necessary to state the safety of using steel mill application, including the use of other crop species, but PM is a promising waste for soil Zn fertilization.


Assuntos
Oryza , Poluentes do Solo , Humanos , Chumbo , Solo , Poluentes do Solo/análise , Aço , Zinco/análise
11.
Environ Sci Pollut Res Int ; 28(9): 11279-11288, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33113065

RESUMO

The heavy metal mercury (Hg) is one of the most complex and toxic pollutants. When present in soils, it may impair plant growth, but the intensity of damage depends on the physical-chemical properties of the soil such as pH, clay, and organic matter content, which in turn affects Hg sorption and bioavailability. Understanding Hg potential damage to staple food crops is of paramount relevance. Here, we evaluated the physiological effects of Hg in Phaseolus vulgaris (common bean) and Avena sativa (oat) cultivated in two Oxisols with contrasting properties: Rhodic Acrudox (RA) and Typic Hapludox (TH). We performed four independent experiments (one per species/soil combination) that lasted 30 days each. Treatments were composed by HgCl2 concentrations in soils (0 to 80 mg kg-1 Hg). At the end of the experiment, we determined the impact of Hg on photosynthesis, nutritional status, and oxidative stress. Cultivation in TH contaminated with Hg resulted in oxidative stress in common bean and decreased photosynthesis/P accumulation in oat. No deleterious effects on physiological variables were detected in both species when cultivated in the RA soil. In general, we conclude that the lower Hg sorption in the TH soil resulted in toxicity-like responses, while acclimation-like responses were observed in plants cultivated in RA, reinforcing soil physical-chemical properties as key features driving Hg toxicity in Oxisols. Graphical abstract.


Assuntos
Mercúrio , Phaseolus , Poluentes do Solo , Avena , Mercúrio/análise , Solo , Poluentes do Solo/análise
12.
Chemosphere ; 254: 126904, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32957297

RESUMO

Estimating bioaccessible content of mercury in soils is essential in evaluating risks that contaminated soils pose. In this study, soil samples spiked with HgCl2 through adsorption were used to test the effects of liming, soil organic matter, soil depth, and Hg concentration on the following bioaccessibility tests: dilute nitric acid at room temperature, dilute nitric acid at body temperature, Simplified Bioaccessibility Extraction Test (SBET) method, and gastric phase of the In vitro Gastrointestinal (IVG) protocol. Soil and sediment samples from Descoberto, Minas Gerais (Brazil), a city with a well-known record of Hg contamination from artisanal mining, were subjected to these bioaccessibility tests for the first time, and the different methods of estimating bioaccessible content were compared. Bioaccessible fractions in spiked samples ranged from 10% to 60%, and this high bioaccessibility was due to the highly soluble species of Hg and the short time under adsorption. In general, clay and organic matter decreased bioaccessible content. Although the soil in Descoberto is undoubtedly polluted, mercury bioaccessibility in that area is low. In general, dilute nitric acid estimated higher bioaccessible content in soil samples, whereas the SBET method estimated higher bioaccessible content in sediment samples. In multivariate analysis, two groups of bioaccessibility tests arise: one with the two nitric acid tests, and the other with SBET and the gastric phase of the IVG protocol. The addition of pepsin and glycine in the last two tests suggests a more reliable test for assessing mercury bioaccessibility.


Assuntos
Argila/química , Substâncias Húmicas/análise , Mercúrio/análise , Mineração , Poluentes do Solo/análise , Solo/química , Adsorção , Disponibilidade Biológica , Brasil , Cidades , Mucosa Gástrica/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Mercúrio/metabolismo , Modelos Biológicos , Ácido Nítrico/química , Poluentes do Solo/metabolismo
13.
Chemosphere ; 257: 127114, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32480084

RESUMO

Problems related to specificity and re-precipitation of metals in sequential chemical extractions can impair their routine use. In order to test the efficiency of a sequential chemical procedure, model compounds composed by soil components commonly found in tropical soils such as goethite, Al-goethite, ferrihydrite, hematite, bauxite, and humic acid were incubated with either Hg(NO3)2 or HgSO4 and submitted to chemical extraction. The procedure aims to assess: (i) water soluble Hg; (ii) bioaccessible Hg at pH near human stomach; (iii) Hg associated with organic matter; (iv) reduced Hg; (v) Hg associated with Fe, Al, and Mn oxides; and, (vi) residual Hg. This procedure was also tested via single and sequential extractions using the surface and subsurface samples of two tropical soils, i.e., a Rhodic Acrudox and a Typic Hapludox, with and without lime application. Soil samples were submitted to an adsorption experiment with HgCl2 and a high adsorption percentage was observed. The majority of Hg at both single and sequential procedure was extracted by an acetic acid solution (pH = 2). Liming, soil depth, and soil type were not determinative on Hg extractability. The sequential extraction applied showed a lack specificity of Hg fractions, confirmed by the model components.


Assuntos
Mercúrio/análise , Poluentes do Solo/análise , Adsorção , Compostos de Cálcio , Fracionamento Químico , Humanos , Óxidos , Solo/química , Água
14.
Cancers (Basel) ; 12(3)2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32197468

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is extremely aggressive, has an unfavorable prognosis, and there are no biomarkers for early detection of the disease or identification of individuals at high risk for morbidity or mortality. The cellular and molecular complexity of PDAC leads to inconsistences in clinical validations of many proteins that have been evaluated as prognostic biomarkers of the disease. The tumor secretome, a potential source of biomarkers in PDAC, plays a crucial role in cell proliferation and metastasis, as well as in resistance to treatments, which together contribute to a worse clinical outcome. The massive amount of proteomic data from pancreatic cancer that has been generated from previous studies can be integrated and explored to uncover secreted proteins relevant to the diagnosis and prognosis of the disease. The present study aimed to perform an integrated meta-analysis of PDAC proteome and secretome public data to identify potential biomarkers of the disease. Our meta-analysis combined mass spectrometry data obtained from two systematic reviews of the pancreatic cancer literature, which independently selected 20 studies of the secretome and 35 of the proteome. Next, we predicted the secreted proteins using seven in silico tools or databases, which identified 39 secreted proteins shared between the secretome and proteome data. Notably, the expression of 31 genes of these secretome-related proteins was upregulated in PDAC samples from The Cancer Genome Atlas (TCGA) when compared to control samples from TCGA and The Genotype-Tissue Expression (GTEx). The prognostic value of these 39 secreted proteins in predicting survival outcome was confirmed using gene expression data from four PDAC datasets (validation set). The gene expression of these secreted proteins was able to distinguish high- and low-survival patients in nine additional tumor types from TCGA, demonstrating that deregulation of these secreted proteins may also contribute to the prognosis in multiple cancers types. Finally, we compared the prognostic value of the identified secreted proteins in PDAC biomarkers studies from the literature. This analysis revealed that our gene signature performed equally well or better than the signatures from these previous studies. In conclusion, our integrated meta-analysis of PDAC proteome and secretome identified 39 secreted proteins as potential biomarkers, and the tumor gene expression profile of these proteins in patients with PDAC is associated with worse overall survival.

15.
Genet Mol Biol ; 43(1): e20180285, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31429857

RESUMO

Duplication of the short arm of chromosome 12 is a rare chromosomal abnormality that may arise de novo or result from malsegregation of a balanced parental translocation. This study comprises the clinical description, cytogenetic and cytogenomic analyses and genotype-phenotype correlation in a patient with facial dysmorphism, developmental delay and intellectual impairment caused by non-mosaic partial duplication and a paracentric inversion 12p. The patient's GTG-banded karyotype was 46,XX,invdup(12)(pter → p13.32::p11.1 → p13.31::p13.31 → qter). A genetic gain of approximately 28 Mb was detected in the chromosomal region arr[GRCh37]12p13.31-p11.1(6914072_34756209)x3. The chromosomal alteration seen in our patient is described as "pure" partial duplication 12p. In most cases, duplication 12p phenotype is characterized by dysmorphic features, multiple congenital anomalies and intellectual disability. A small number of cases in literature have described genes associated with neurodevelopmental disease, such as ING4, CHD4, MFAP5, GRIN2B, SOX5, SCN8A and PIANP. In our patient the duplication 12p was de novo. This study should contribute to the genotype-phenotype correlation in partial duplication 12p cases.

16.
Int J Mol Sci ; 20(8)2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31013615

RESUMO

Cancer cachexia is a multifactorial syndrome that leads to significant weight loss. Cachexia affects 50%-80% of cancer patients, depending on the tumor type, and is associated with 20%-40% of cancer patient deaths. Besides the efforts to identify molecular mechanisms of skeletal muscle atrophy-a key feature in cancer cachexia-no effective therapy for the syndrome is currently available. MicroRNAs are regulators of gene expression, with therapeutic potential in several muscle wasting disorders. We performed a meta-analysis of previously published gene expression data to reveal new potential microRNA-mRNA networks associated with muscle atrophy in cancer cachexia. We retrieved 52 differentially expressed genes in nine studies of muscle tissue from patients and rodent models of cancer cachexia. Next, we predicted microRNAs targeting these differentially expressed genes. We also include global microRNA expression data surveyed in atrophying skeletal muscles from previous studies as background information. We identified deregulated genes involved in the regulation of apoptosis, muscle hypertrophy, catabolism, and acute phase response. We further predicted new microRNA-mRNA interactions, such as miR-27a/Foxo1, miR-27a/Mef2c, miR-27b/Cxcl12, miR-27b/Mef2c, miR-140/Cxcl12, miR-199a/Cav1, and miR-199a/Junb, which may contribute to muscle wasting in cancer cachexia. Finally, we found drugs targeting MSTN, CXCL12, and CAMK2B, which may be considered for the development of novel therapeutic strategies for cancer cachexia. Our study has broadened the knowledge of microRNA-regulated networks that are likely associated with muscle atrophy in cancer cachexia, pointing to their involvement as potential targets for novel therapeutic strategies.


Assuntos
Caquexia/etiologia , Redes Reguladoras de Genes , MicroRNAs/genética , Neoplasias/complicações , Neoplasias/genética , Caquexia/metabolismo , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Humanos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Neoplasias/metabolismo , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Reprodutibilidade dos Testes , Transcriptoma
17.
Biosci. j. (Online) ; 30(5): 1380-1388, sept./oct. 2014.
Artigo em Português | LILACS | ID: biblio-946588

RESUMO

O fósforo é um importante macronutriente, requerido por todas as plantas para crescimento, desenvolvimento e reprodução, sendo o fator de produção mais importante para a agricultura após a calagem em solos sob vegetação de Cerrado. Assim, objetivou-se avaliar o desenvolvimento e produção do feijão guandu submetido à adubação fosfatada, sem inoculação de sementes, em Latossolo Vermelho do Cerrado em primeiro cultivo. O experimento foi conduzido em casa de vegetação no período de agosto a novembro de 2010. Utilizaram-se vasos contendo 3 dm-3 de solo coletado na profundidade de 0-0,20 m em área de Cerrado. O delineamento experimental foi inteiramente casualizado, com seis doses de fósforo (P2O5): 0; 50; 100; 150; 200 e 250 mg dm-3 em quatro repetições. Houve efeito significativo a 5% de probabilidade para todas as variáveis avaliadas com ajuste aos modelos quadrático e linear de regressão. O melhor desenvolvimento e produção de feijão guandu ocorre no intervalo de doses de fósforo de 162 a 225 mg dm-3. O feijão guandu responde de forma positiva a adubação fosfatada, sem a inoculação de sementes em Latossolo Vermelho do Cerrado em área de primeiro cultivo.


Phosphorus is an important macronutrient required by all plants for growth, development and reproduction, and the most important production factor for agriculture after liming in soils under Cerrado vegetation. Thus, the objective was to evaluate the development and production of pigeonpea subjected to fertilization without inoculation of Cerrado Oxisol in first cultivation. The experiment was conducted in a greenhouse in August-November 2010. We used 3 dm3 pots containing soil collected at 0-20 cm depth in the Cerrado. The experimental design was completely randomized design with six levels of phosphorus (P2O5): 0; 50; 100; 150; 200, e 250 mg dm-3 with four replications. There was a significant effect at 5% probability for all variables adjusted for the quadratic and linear regression. The best development and production of pigeonpea occurs within phosphorus levels of 162 the 225 mg dm-3. The pigeonpea respond positively to fertilization, without the inoculation of seeds in the soil of the Cerrado in first cultivation area.


Assuntos
Fósforo , Produção Agrícola , Cajanus/crescimento & desenvolvimento , Esterco
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