Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 559
Filtrar
1.
Blood ; 137(19): 2681-2693, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33529319

RESUMO

Patients with isolated pulmonary embolism (PE) have a distinct clinical profile from those with deep vein thrombosis (DVT)-associated PE, with more pulmonary conditions and atherosclerosis. These findings suggest a distinct molecular pathophysiology and the potential involvement of alternative pathways in isolated PE. To test this hypothesis, data from 532 individuals from the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism Project, a multicenter prospective cohort study with extensive biobanking, were analyzed. Targeted, high-throughput proteomics, machine learning, and bioinformatic methods were applied to contrast the acute-phase plasma proteomes of isolated PE patients (n = 96) against those of patients with DVT-associated PE (n = 276) or isolated DVT (n = 160). This resulted in the identification of shared molecular processes between PE phenotypes, as well as an isolated PE-specific protein signature. Shared processes included upregulation of inflammation, response to oxidative stress, and the loss of pulmonary surfactant. The isolated PE-specific signature consisted of 5 proteins: interferon-γ, glial cell line-derived neurotrophic growth factor, polypeptide N-acetylgalactosaminyltransferase 3, peptidyl arginine deiminase type-2, and interleukin-15 receptor subunit α. These proteins were orthogonally validated using cis protein quantitative trait loci. External replication in an independent population-based cohort (n = 5778) further validated the proteomic results and showed that they were prognostic for incident primary isolated PE in individuals without history of VTE (median time to event: 2.9 years; interquartile range: 1.6-4.2 years), supporting their possible involvement in the early pathogenesis. This study has identified molecular overlaps and differences between VTE phenotypes. In particular, the results implicate noncanonical pathways more commonly associated with respiratory and atherosclerotic disease in the acute pathophysiology of isolated PE.


Assuntos
Proteoma , Embolia Pulmonar/metabolismo , Transcriptoma , Proteínas de Fase Aguda/biossíntese , Adulto , Idoso , Aterosclerose/complicações , Comorbidade , Conjuntos de Dados como Assunto , Feminino , Seguimentos , Regulação da Expressão Gênica , Fator Neurotrófico Derivado de Linhagem de Célula Glial/biossíntese , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Humanos , Interferon gama/biossíntese , Interferon gama/genética , Subunidade alfa de Receptor de Interleucina-15/biossíntese , Subunidade alfa de Receptor de Interleucina-15/genética , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , N-Acetilgalactosaminiltransferases/biossíntese , N-Acetilgalactosaminiltransferases/genética , Estresse Oxidativo , Estudos Prospectivos , Mapas de Interação de Proteínas , Proteína-Arginina Desiminase do Tipo 2/biossíntese , Proteína-Arginina Desiminase do Tipo 2/genética , Embolia Pulmonar/genética , Embolia Pulmonar/fisiopatologia , Surfactantes Pulmonares , Locos de Características Quantitativas , Tromboembolia Venosa/metabolismo , Polipeptídeo N-Acetilgalactosaminiltransferase
2.
Epidemiol Infect ; 148: e164, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32713370

RESUMO

The emergence of 2019 novel coronavirus disease (COVID-19) is currently a global concern. In this study, our goal was to explore the changing expression levels of acute-phase reaction proteins (APRPs) in the serum of COVID-19 patients and to elucidate the immunological characteristics of COVID-19. In the study design, we recruited 72 COVID-19 patients, including 22 cases of mild degree, 38 cases of moderate degree and 12 cases of severe degree. We also recruited 20 patients with community-acquired pneumonia (CAP) and 20 normal control subjects as a comparison. Fasting venous blood was taken to detect the content of complement 3 (C3), complement 4 (C4), C-reactive protein (CRP), serum amyloid A (SAA) and prealbumin (PA). When compared the COVID-19 group with the CAP and normal control groups, respectively, the mean value of CRP and SAA in the COVID-19 group (including mild, moderate and severe patients) had increased significantly (P < 0.01), whereas the mean values of C3, C4 and PA decreased (P < 0.01). For the asymptomatic or mild symptomatic patients with COVID-19, the actual aggravation of disease may be more advanced than the clinical appearances. Meanwhile, the statistical analyses indicated that the development of COVID-19 brought about a significant increase in the content of CRP and SAA (P < 0.01), and a decline in the content of C3, C4 and PA (P < 0.01). These findings suggested that the changes in the level of APRPs could be used as indicators to identify the degree and progression of COVID-19, and the significant changes might demonstrate the aggravation of disease. This study provided a new approach to improve the clinical management plan and prognosis of COVID-19.


Assuntos
Proteínas de Fase Aguda/análise , Proteínas de Fase Aguda/biossíntese , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Adulto , Idoso , Proteína C-Reativa/análise , Proteína C-Reativa/biossíntese , COVID-19 , Estudos de Casos e Controles , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/imunologia , Complemento C3/análise , Complemento C3/biossíntese , Complemento C4/análise , Complemento C4/biossíntese , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia/sangue , Pneumonia/imunologia , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Pré-Albumina/análise , Pré-Albumina/biossíntese , Prognóstico , Proteína Amiloide A Sérica/análise , Proteína Amiloide A Sérica/biossíntese , Índice de Gravidade de Doença , Adulto Jovem
3.
ESC Heart Fail ; 6(1): 89-97, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30367561

RESUMO

AIMS: Cachexia is a severe consequence of cancer. Although cancer-induced heart atrophy leads to cardiac dysfunction and heart failure (HF), biomarkers for their diagnosis have not been identified. Neutrophil gelatinase-associated lipocalin (NGAL) is an aldosterone-responsive gene increased in HF. We studied NGAL and its association with aldosterone levels in a model of cancer cachexia-induced cardiomyopathy. METHODS AND RESULTS: Rats were injected with Yoshida 108 AH-130 hepatoma cells to induce tumour. Cachectic rats were treated daily, for 16 days, with placebo or with 5 or 50 mg/kg/day of spironolactone. Cardiac function was analysed by echocardiography at baseline and at Day 11. Weight loss and atrophy of lean body and fat mass of cachectic rats were significantly attenuated by spironolactone. Cardiac dysfunction of tumour-bearing rats was improved by spironolactone. Plasma aldosterone was up-regulated from 337 ± 7 pg/mL in sham animals to 591 ± 31 pg/mL in the cachectic rats (P < 0.001 vs. sham). Treatment with 50 or 5 mg/kg/day of spironolactone reduced plasma aldosterone to 396 ± 22 and 391 ± 25 pg/mL (P < 0.01 vs. placebo). Plasma levels of NGAL were also increased in cachectic rats (1.462 ± 0.3603 µg/mL) than in controls (0.0936 ± 6 µg/mL, P < 0.001). Spironolactone treatment (50 mg/kg/day) significantly reduced cardiac mRNA and protein NGAL levels (P < 0.05 and P < 0.001 vs. placebo, respectively). NGAL mRNA and protein levels were overexpressed in cachectic animal hearts treated with placebo, compared with control (P < 0.05 and P < 0.01 vs. sham). Spironolactone treatment at 50 mg/kg/day reduced significantly cardiac NGAL (P < 0.05 and P < 0.001 vs. placebo). CONCLUSIONS: Cancer cachexia induced increased levels of aldosterone and NGAL, contributing to worsening cardiac damage in cancer cachexia-induced cardiomyopathy. Spironolactone treatment may greatly attenuate cardiac dysfunction and lean mass atrophy associated with cancer cachexia.


Assuntos
Proteínas de Fase Aguda , Caquexia , Cardiomiopatias , Regulação Neoplásica da Expressão Gênica , Lipocalinas , Miocárdio , Neoplasias Experimentais , Proteínas Proto-Oncogênicas , Animais , Masculino , Ratos , Proteínas de Fase Aguda/biossíntese , Proteínas de Fase Aguda/genética , Western Blotting , Caquexia/complicações , Caquexia/metabolismo , Cardiomiopatias/etiologia , Cardiomiopatias/genética , Cardiomiopatias/metabolismo , Lipocalina-2 , Lipocalinas/biossíntese , Lipocalinas/genética , Miocárdio/metabolismo , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/genética , Distribuição Aleatória , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA Neoplásico/genética
4.
BMC Nephrol ; 19(1): 168, 2018 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-29980183

RESUMO

BACKGROUND: We sought to confirm that neutrophil gelatinase-associated lipocalin (NGAL) protects against apoptosis during endotoxemia. METHODS: Endotoxemia was induced in rats with lipopolysaccharide (LPS; 3.5 mg/kg) and serum creatinine (SCr), urinary NGAL (uNGAL), renal histopathology confirmed acute kidney injury (AKI). Renal caspase 3 and NGAL were assayed with immunohistochemistry 6 h later. A HK-2 cell model was used in which NGAL and caspase 3 mRNA were evaluated by qRT-PCR within 6 h after LPS (50 µM) treatment, and correlations were studied. NGAL and caspase 3 mRNA expression were measured after delivering NGAL siRNA in HK-2 cells and apoptosis was measured with TUNEL and flow cytometry. RESULTS: SCr and uNGAL were significantly increased after LPS treatment and renal morphology data indicated AKI and renal tubular epithelial cell apoptosis. Caspase 3 and NGAL were predominantly expressed in the tubular epithelial cells and there was a correlation between caspase 3 and NGAL protein (r = 0.663, p = 0.01). In vitro, there was a strong correlation between caspase 3 and NGAL mRNA in LPS-injured HK-2 cells within 24 h (r = 0.448, p < 0.05). Suppressing the NGAL gene in HK-2 cells increased caspase 3 mRNA 4.5-fold and apoptosis increased 1.5-fold after LPS treatment. CONCLUSIONS: NGAL is associated with caspase 3 in renal tubular cells with endotoxin-induced kidney injury, and may regulate its expression and inhibit apoptosis.


Assuntos
Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/prevenção & controle , Proteínas de Fase Aguda/biossíntese , Apoptose/fisiologia , Túbulos Renais/metabolismo , Lipocalinas/biossíntese , Lipopolissacarídeos/toxicidade , Proteínas Proto-Oncogênicas/biossíntese , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Humanos , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/patologia , Lipocalina-2 , Masculino , Ratos , Ratos Sprague-Dawley
5.
Epigenomics ; 10(4): 395-408, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29587528

RESUMO

AIM: To examine how enteral feeding affects the intestinal epigenome and gene expression just after preterm birth. MATERIALS & METHODS: Intestinal tissue from preterm pigs, modeling preterm infants, was collected at birth and 5 days after gradual introduction of infant formula or bovine colostrum. The intestinal tissue was analyzed by reduced representation bisulfite sequencing and real-time qPCR. RESULTS: Relative to colostrum, formula increased bacterial epithelial adherence and lipopolysaccharide binding protein (LBP) expression, which was regulated by promoter methylation. Diet-dependent changes in DNA methylation and/or mRNA expression were related to innate immune response, hypoxia, angiogenesis and epithelial-mesenchymal transition pathways (e.g., TTC38, IL8, C3, HIF1A and VEGFR1). CONCLUSION: Epigenetic changes may mediate important effects of the first feeding on intestinal development in preterm neonates.


Assuntos
Metilação de DNA , Dieta , Intestinos , Proteínas de Fase Aguda/biossíntese , Proteínas de Fase Aguda/genética , Animais , Proteínas de Transporte/biossíntese , Proteínas de Transporte/genética , Colostro , Nutrição Enteral , Imunidade Inata/genética , Fórmulas Infantis , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/genética , Regiões Promotoras Genéticas , Transdução de Sinais , Suínos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
Macromol Biosci ; 17(8)2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28508430

RESUMO

A ternary complex comprising plasmid DNA, lipopolysaccharide-binding peptide (LBP), and deoxycholic acid-conjugated polyethylenimine (PEI-DA) is prepared for combinational therapy of acute lung injury (ALI). The LBP is designed as an anti-inflammatory peptide based on the lipopolysaccharide (LPS)-binding domain of HMGB-1. In vitro cytokine assays show that LBP reduces levels of proinflammatory cytokines by inhibiting LPS. PEI-DA is synthesized as the gene carrier by conjugation of deoxycholic acid to low-molecular weight polyethylenimine (2 kDa, PEI2k). PEI-DA has higher transfection efficiency than high-molecular weight polyethylenimine (25 kDa, PEI25k). The ternary complex of an HO-1 plasmid (pHO-1), PEI-DA, and LBP is prepared as a combinational system to deliver the therapeutic gene and peptide. The transfection efficiency of the ternary complex is higher than that of the pHO-1/PEI-DA binary complex. The ternary complex also reduces TNF-α secretion in LPS-activated Raw264.7 macrophage cells. Administration of the ternary complex into the lungs of an animal ALI model by intratracheal injection induces HO-1 expression and reduces levels of proinflammatory cytokines more efficiently than the pHO-1/PEI-DA binary complex or LBP alone. In addition, the ternary complex reduces inflammation in the lungs. Therefore, the pHO-1/PEI-DA/LBP ternary complex may be an effective treatment for ALI.


Assuntos
Lesão Pulmonar Aguda , Proteínas de Fase Aguda , Proteínas de Transporte , Ácido Desoxicólico , Técnicas de Transferência de Genes , Heme Oxigenase-1 , Glicoproteínas de Membrana , Proteínas de Membrana , Polietilenoimina , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/terapia , Proteínas de Fase Aguda/biossíntese , Proteínas de Fase Aguda/genética , Animais , Proteínas de Transporte/biossíntese , Proteínas de Transporte/genética , Ácido Desoxicólico/química , Ácido Desoxicólico/farmacologia , Heme Oxigenase-1/biossíntese , Heme Oxigenase-1/genética , Masculino , Glicoproteínas de Membrana/biossíntese , Glicoproteínas de Membrana/genética , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Polietilenoimina/química , Polietilenoimina/farmacologia , Células RAW 264.7
7.
Alcohol Clin Exp Res ; 41(3): 562-570, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28055129

RESUMO

BACKGROUND: Long-term excessive alcohol intake predisposes to infectious diseases. The hepatic acute-phase response is a component of the innate immune system and is part of the first line of defense against invading pathogens, which may be compromised by alcohol. We aimed to investigate whether an induced acute-phase response is impaired in long-term ethanol (EtOH)-fed rats. METHODS: For 6 weeks, rats were either fed a Lieber-DeCarli EtOH-containing (36% as calories) liquid diet ad libitum or calorically pair-fed. Then, the rats were injected intraperitoneally with a low dose of lipopolysaccharide (LPS) (0.5 mg/kg) to induce an acute-phase response. Two hours after LPS, we measured the plasma concentrations of an array of inflammatory cytokines. Twenty-four hours after LPS, we measured the hepatic mRNA expression and serum concentrations of prominent rat acute-phase proteins. RESULTS: EtOH-fed rats showed either no liver histopathological changes or varying degrees of steatosis. EtOH feeding decreased the spontaneous liver mRNA expression of the prevailing acute-phase protein alpha-2-macroglobulin (α2M) by 30% (p < 0.01). LPS immediately increased plasma tumor necrosis factor-alpha and interleukin-6 more than 100-fold in both feeding groups (p < 0.001, all) and approximately twice as much in the EtOH-fed rats (p < 0.05 and p = 0.08, respectively). LPS also induced a variable but marked amplification of (α2M), haptoglobin, alpha-1-acid glycoprotein, and lipocalin-2 liver mRNA expression levels and serum concentrations in both feeding groups (p ≤ 0.01 to 0.001). However, the LPS-induced increases in serum (α2M) and haptoglobin were less pronounced in the EtOH-fed rats, averaging approximately 60% of the concentrations in the pair-fed rats (p < 0.01 and p < 0.001, respectively). CONCLUSIONS: Long-term EtOH exposure in rats reduces the spontaneous hepatic mRNA expression of (α2M) and markedly impairs the hepatic acute-phase response to endotoxin, despite higher pro-inflammatory cytokine release. The same phenomenon may contribute to the increased susceptibility to infections observed in humans with long-term excessive alcohol intake.


Assuntos
Proteínas de Fase Aguda/biossíntese , Reação de Fase Aguda/metabolismo , Endotoxinas/toxicidade , Etanol/administração & dosagem , Fígado/metabolismo , Reação de Fase Aguda/induzido quimicamente , Reação de Fase Aguda/tratamento farmacológico , Animais , Feminino , Mediadores da Inflamação/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Distribuição Aleatória , Ratos , Ratos Wistar
8.
Ren Fail ; 38(9): 1483-1495, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27756197

RESUMO

Diabetic nephropathy is a serious microvascular complication and one of the main causes of end-stage renal disease. L-Glutamine (LG) is naturally occurring amino acids with antidiabetic and antioxidant potential. The aim of present investigation was to evaluate the potential of LG against streptozotocin (STZ)-induced diabetic nephropathy (DN) in laboratory rats. DN was induced in male Wistar rats (200-220 g) by intraperitoneal administration of STZ (55 mg/kg). Animals were treated orally with either distilled water (10 mg/kg) or LG (250, 500, and 1000 mg/kg) or Sitagliptin (5 mg/kg). Various biochemical, molecular, and histological (hematoxylin-eosin and Masson's trichrome stain) parameters were assessed. Administration of LG (500 and 1000 mg/kg) significantly inhibited (p < .05) STZ-induced alterations in serum and urine biochemistry (urine creatinine, uric acid, albumin, and BUN). It also significantly increased creatinine clearance rate. STZ induced increase in renal oxidonitrosative stress was significantly decreased (p < .05) by LG (500 and 1000 mg/kg) treatment. Upregulated renal KIM-1, NGAL, TGF-ß1, and collagen-1 mRNA expression after STZ administration was significantly inhibited (p < .05) by LG (500 and 1000 mg/kg) treatment. Correlation analysis also revealed that antidiabetic potential of LG attenuates STZ-induced elevated renal KIM-1, NGAL, TGF-ß1, and collagen-1 mRNA expression. Histopathological alteration induced by STZ in renal tissue was ameliorated by LG treatment. In conclusion, results of present investigation suggest that treatment with LG ameliorated STZ-induced DN via the inhibition of oxidonitrosative stress as well as downregulation of KIM-1, NGAL, TGF-ß1, and collagen-1 mRNA expressions.


Assuntos
Proteínas de Fase Aguda/genética , Moléculas de Adesão Celular/genética , Colágeno Tipo I/genética , Nefropatias Diabéticas/tratamento farmacológico , Regulação da Expressão Gênica , Glutamina/farmacologia , Lipocalinas/genética , Proteínas Proto-Oncogênicas/genética , Fator de Crescimento Transformador beta1/genética , Proteínas de Fase Aguda/biossíntese , Animais , Moléculas de Adesão Celular/biossíntese , Colágeno Tipo I/biossíntese , Diabetes Mellitus Experimental , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Modelos Animais de Doenças , Lipocalina-2 , Lipocalinas/biossíntese , Masculino , Proteínas Proto-Oncogênicas/biossíntese , RNA/genética , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta1/metabolismo
9.
J Recept Signal Transduct Res ; 36(4): 429-34, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27087673

RESUMO

INTRODUCTION: Trauma is one of the causes of peripheral nerve injuries. Free radicals increase after tissue damage. Free radicals are usually scavenged and detoxified by antioxidants. In this study, we assessed the antioxidative role of the NGAL molecule in sciatic nerve repair in rats. MATERIALS AND METHODS: The sciatic nerves of 40 rats were crushed and the total mRNA of samples from day 1 and 3 and week 1, 3, 5 post injury was extracted. The expression of the NGAL gene was confirmed by RT-PCR. For immunohistochemistry analysis, the samples were fixed in paraformaldehyde and cut in 20 micrometer slices by cryostat. RESULTS: The expression of NGAL significantly upregulated in day 1, 3 and week 1 following the crushing of sciatic nerves in comparison with the intact nerves. Immunohistochemistry results also confirmed the protein expression of this gene. DISCUSSION: The NGAL molecule showed upregulation in the degeneration process after nerve injury, so it may play an important role in nerve repair.


Assuntos
Proteínas de Fase Aguda/biossíntese , Lipocalinas/biossíntese , Regeneração Nervosa/genética , Nervos Periféricos/metabolismo , Proteínas Proto-Oncogênicas/biossíntese , Nervo Isquiático/metabolismo , Proteínas de Fase Aguda/genética , Animais , Sequestradores de Radicais Livres/metabolismo , Regulação da Expressão Gênica , Humanos , Lipocalina-2 , Lipocalinas/genética , Nervos Periféricos/patologia , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Nervo Isquiático/lesões , Nervo Isquiático/fisiopatologia
10.
Food Nutr Bull ; 37 Suppl 1: S29-36, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26857118

RESUMO

BACKGROUND: Protein quality refers to the amounts and ratios of essential amino acids in a food. Two methods most commonly used for determining protein quality are the protein digestibility-corrected amino acid score (PDCAAS) and the digestible indispensible amino acid score (DIAAS). OBJECTIVE: To use existing literature to compare different amino acid profiles and PDCAAS and DIAAS scores in individuals with acute inflammation and to assess their relationship with weight gain in children with severe acute malnourished (SAM). METHODS: A series stable isotope studies were previously conducted in children with SAM and acute infection, and these data were reviewed with respect to protein synthesis. Eleven published treatment trials for SAM with different therapeutic foods were analyzed to examine the relationship between protein quality scores with weight gain (g/kg/d). Protein scores were calculated with the PDCAAS and DIAAS amino acid reference patterns. A DIAAS score adjusted for the higher weight gain expected in malnourished children was also used. Bivariate correlation analysis was used to examine this relationship. RESULTS: The protein kinetic data supported the hypothesis that a balance of amino acids that matches the composition of acute-phase proteins maximizes amino acid synthesis. Protein quality scores were highly correlated with the rate of weight gain in recovery from SAM, and the DIAAS scoring system adjusted for the higher expected weight gain had the strongest correlation with the observed weight gain. CONCLUSION: Protein quality scores must account for physiologic status so that they better match with needs and thus better promote health.


Assuntos
Transtornos da Nutrição Infantil/dietoterapia , Proteínas Alimentares/administração & dosagem , Valor Nutritivo , Aumento de Peso , Proteínas de Fase Aguda/biossíntese , Aminoácidos/administração & dosagem , Aminoácidos/análise , Criança , Transtornos da Nutrição Infantil/complicações , Transtornos da Nutrição Infantil/metabolismo , Pré-Escolar , Digestão , Alimentos , Humanos , Lactente , Recém-Nascido , Infecções/complicações , Infecções/metabolismo , Inflamação/metabolismo , Necessidades Nutricionais
11.
Hum Mol Genet ; 25(6): 1192-202, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26744329

RESUMO

Muscular dystrophy (MD) is associated with mutations in genes that stabilize the myofiber plasma membrane, such as through the dystrophin-glycoprotein complex (DGC). Instability of this complex or defects in membrane repair/integrity leads to calcium influx and myofiber necrosis leading to progressive dystrophic disease. MD pathogenesis is also associated with increased skeletal muscle protease levels and activity that could augment weakening of the sarcolemma through greater degradation of cellular attachment complexes. Here, we observed a compensatory increase in the serine protease inhibitor Serpina3n in mouse models of MD and after acute muscle tissue injury. Serpina3n muscle-specific transgenic mice were generated to model this increase in expression, which reduced the activity of select proteases in dystrophic skeletal muscle and protected muscle from both acute injury with cardiotoxin and from chronic muscle disease in the mdx or Sgcd(-/-) MD genetic backgrounds. The Serpina3n transgene mitigated muscle degeneration and fibrosis, reduced creatine kinase serum levels, restored running capacity on a treadmill and reduced muscle membrane leakiness in vivo that is characteristic of mdx and Sgcd(-/-) mice. Mechanistically, we show that increased Serpina3n promotes greater sarcolemma membrane integrity and stability in dystrophic mouse models in association with increased membrane residence of the integrins, the DGC/utrophin-glycoprotein complex of proteins and annexin A1. Hence, Serpina3n blocks endogenous increases in the activity of select skeletal muscle resident proteases during injury or dystrophic disease, which stabilizes the sarcolemma leading to less myofiber degeneration and increased regeneration. These results suggest the use of select protease inhibitors as a strategy for treating MD.


Assuntos
Proteínas de Fase Aguda/biossíntese , Proteínas de Fase Aguda/genética , Distrofia Muscular Animal/metabolismo , Distrofia Muscular Animal/terapia , Serpinas/biossíntese , Serpinas/genética , Proteínas de Fase Aguda/metabolismo , Animais , Cálcio/metabolismo , Membrana Celular/metabolismo , Modelos Animais de Doenças , Distrofina/genética , Distrofina/metabolismo , Feminino , Integrinas/genética , Integrinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Camundongos Transgênicos , Músculo Esquelético/metabolismo , Distrofia Muscular Animal/genética , Sarcolema/metabolismo , Serpinas/metabolismo , Transgenes , Regulação para Cima , Utrofina/genética , Utrofina/metabolismo
12.
Int J Oncol ; 48(1): 84-98, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26573874

RESUMO

Tumor initiating cancer stem-like cells (TICSCs) have recently become the object of intensive study. Human-Lipocalin-2 (hLCN2) acts as a biomarker for cancers. The aim of the present study was to explore new insights regarding the potential role of LCN2 in inducing epithelial to mesenchymal transition (EMT) by transfecting LCN2 into CD133+-A549-TICSCs and its cross-talk with the NF-κB signaling pathway in adenocarcinoma of the lung. Furthermore, EMT was confirmed by transcriptomic analysis, immunoblotting and immunocyto/histochemical analyses. Tumorigenesis and metastasis were confirmed by molecular therapeutics tracer 2DG infrared optical probe in BALB/cSIc-nude mice. It was observed that the CD133+-expressing-LCN2-A549 TICSCs population increased in adenocarcinoma of the lung compared to the normal lung tissue. The expressions of genes involved in stemness, adhesion, motility and drug efflux was higher in these cells than in their non-LCN2 expressing counterparts. The present study revealed that elevated expression of LCN2 significantly induced metastasis via EMT. Overexpression of LCN2 significantly increased stemness and tumor metastasis by modulating NF-κB cellular signaling. BRM270, a novel inhibitor of NF-κB plays a significant role in the EMT reversal. BRM270, a naturaceutical induces cell shrinkage, karyorrhexis and programmed cell death (PCD) which were observed by Hoechst 33342 staining while flow cytometry analysis showed significant (P<0.05) decrease in cell population from G0-G1 phases. Also, 2DG guided in vivo model revealed that BRRM270 significantly (P<0.0003) reduced tumor metastasis and increased percent survival in real-time with complete resection. An elaborate study on the novel concept with respect to linking of naturaceutics as selective and potential anticancer agent that eliminates the elevated LCN2 induced EMT and tumor dissemination through cooperation with the NF-κB signaling as the baseline data for the planning of new therapeutic strategies was conducted for the first time. Our results also illustrate a molecular mechanistic approach for 2DG-guided molecular imaging-based cancer therapy using BRM270 as a novel cancer therapeutic drug to enhance the effect of doxorubicin (Dox)-resistant LCN2 induced metastasis of solid tumors in nude mice.


Assuntos
Proteínas de Fase Aguda/genética , Adenocarcinoma/genética , Carcinogênese/genética , Resistencia a Medicamentos Antineoplásicos/genética , Transição Epitelial-Mesenquimal/genética , Lipocalinas/genética , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas/genética , Proteínas de Fase Aguda/biossíntese , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Epigênese Genética/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lipocalina-2 , Lipocalinas/biossíntese , Neoplasias Pulmonares/patologia , Camundongos , NF-kappa B/genética , Metástase Neoplásica , Proteínas Proto-Oncogênicas/biossíntese , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Mol Cell Proteomics ; 15(2): 624-41, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26598643

RESUMO

Site-specific glycosylation analysis is key to investigate structure-function relationships of glycoproteins, e.g. in the context of antigenicity and disease progression. The analysis, though, is quite challenging and time consuming, in particular for O-glycosylated proteins. In consequence, despite their clinical and biopharmaceutical importance, many human blood plasma glycoproteins have not been characterized comprehensively with respect to their O-glycosylation. Here, we report on the site-specific O-glycosylation analysis of human blood plasma glycoproteins. To this end pooled human blood plasma of healthy donors was proteolytically digested using a broad-specific enzyme (Proteinase K), followed by a precipitation step, as well as a glycopeptide enrichment and fractionation step via hydrophilic interaction liquid chromatography, the latter being optimized for intact O-glycopeptides carrying short mucin-type core-1 and -2 O-glycans, which represent the vast majority of O-glycans on human blood plasma proteins. Enriched O-glycopeptide fractions were subjected to mass spectrometric analysis using reversed-phase liquid chromatography coupled online to an ion trap mass spectrometer operated in positive-ion mode. Peptide identity and glycan composition were derived from low-energy collision-induced dissociation fragment spectra acquired in multistage mode. To pinpoint the O-glycosylation sites glycopeptides were fragmented using electron transfer dissociation. Spectra were annotated by database searches as well as manually. Overall, 31 O-glycosylation sites and regions belonging to 22 proteins were identified, the majority being acute-phase proteins. Strikingly, also 11 novel O-glycosylation sites and regions were identified. In total 23 O-glycosylation sites could be pinpointed. Interestingly, the use of Proteinase K proved to be particularly beneficial in this context. The identified O-glycan compositions most probably correspond to mono- and disialylated core-1 mucin-type O-glycans (T-antigen). The developed workflow allows the identification and characterization of the major population of the human blood plasma O-glycoproteome and our results provide new insights, which can help to unravel structure-function relationships. The data were deposited to ProteomeXchange PXD003270.


Assuntos
Proteínas de Fase Aguda/genética , Antígenos Virais de Tumores/genética , Glicopeptídeos/genética , Polissacarídeos/genética , Proteínas de Fase Aguda/biossíntese , Antígenos Virais de Tumores/sangue , Cromatografia de Fase Reversa , Glicopeptídeos/sangue , Glicosilação , Voluntários Saudáveis , Humanos , Interações Hidrofóbicas e Hidrofílicas , Espectrometria de Massas , Mucina-1/sangue , Mucina-1/genética , Polissacarídeos/sangue
14.
Exp Biol Med (Maywood) ; 241(1): 25-30, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26129883

RESUMO

Hypoxia-induced cardiomyocyte apoptosis contributes significantly to the development of numerous cardiac diseases, such as ischemic heart disease, heart failure, etc. Promoting cell survival by inhibiting apoptosis is one of the available strategies to attenuate cardiac dysfunction caused by cardiomyocyte loss. Previous studies have been demonstrated that miR-138 and lipocalin-2 (Lcn2) play important roles in cardiomyocyte apoptosis and survival. We presently determined whether Lcn2 is a target gene of miR-138 involved in hypoxia-induced cardiomyocyte apoptosis. Firstly, mimics of miR-138 were transfected into HL-1 cells to investigate its effect on cell apoptosis. Using 3-(4,5-dimethyl-thiazol-2-y1) 2,5-diphenyl tetrazolium bromide (MTT) and Annexin V-FITC/PI flow cytometer assays, over-expression of miR-138 significantly enhanced the cell growth and significantly attenuated the cell apoptosis in hypoxic conditions. Dual-luciferase reporter gene and western blot results confirmed Lcn2 was a direct target of miR-138. Then, the recombinant plasmid, pcDNA3.1/Lcn2 was transfected into the HL-1 cells that over-expressed miR-138. We further observed that the over-expression of Lcn2 diminished the protection of miR-138 over-expression from hypoxia-induced cell survival and apoptosis. In conclusion, our study demonstrated that up-regulation of miR-138 inhibits the hypoxia-induced cardiomyocyte apoptosis via down-regulating the pro-apoptotic gene expression of Lcn2.


Assuntos
Proteínas de Fase Aguda/antagonistas & inibidores , Proteínas de Fase Aguda/biossíntese , Apoptose , Hipóxia/patologia , Lipocalinas/antagonistas & inibidores , Lipocalinas/biossíntese , MicroRNAs/metabolismo , Miócitos Cardíacos/fisiologia , Proteínas Oncogênicas/antagonistas & inibidores , Proteínas Oncogênicas/biossíntese , Animais , Western Blotting , Sobrevivência Celular , Regulação para Baixo , Perfilação da Expressão Gênica , Genes Reporter , Lipocalina-2 , Luciferases/análise , Luciferases/genética , Camundongos
15.
Int J Clin Exp Pathol ; 8(8): 8857-68, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26464627

RESUMO

To examine the significance of the Neutrophil gelatinase-associated lipocalin (NGAL) in diagnosing head and neck squamous cell carcinoma (HNSCC) and predicting regional metastasis. We first used GEO dataset to analyze the NGAL gene expression in HNSCC. Then, we summarized the characteristics of patients retrospectively selected in clinic. Expression of NGAL protein in human HNSCC tumor, lymph node and normal samples were analyzed using immunohistochemistry. Next, we further investigated the NGAL expression in a tissue microassay to analyze the relationship between NGAL protein expression and TNM stage. Finally, we tested the NGAL protein expression in head and neck cancer cell lines. Analysis of GEO dataset concluded that NGAL gene expression in HNSCC was lower than that in normal tissue (P<0.01). There was no statistically significant difference of NGAL gene expression between T-stage and N-stage (P>0.05). NGAL protein expression in tumor was lower than that in normal tissue (P<0.01). There was no statistically significant difference of NGAL protein expression between metastasis group and non-metastasis group (P>0.05). Expression of NGAL protein was not correlated with TNM stage of HNSCC. Aggressive HNSCC cell lines have lower NGAL protein expression. Our data demonstrated that the expression of NGAL protein was correlated with tumorigenesis of HNSCC, but not with regional metastasis. It may serve as a novel biomarker for prognostic evaluation of patients with HNSCC.


Assuntos
Proteínas de Fase Aguda/biossíntese , Carcinogênese/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Lipocalinas/biossíntese , Invasividade Neoplásica/patologia , Proteínas Proto-Oncogênicas/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Western Blotting , Carcinogênese/genética , Carcinoma de Células Escamosas/genética , Regulação para Baixo , Feminino , Neoplasias de Cabeça e Pescoço/genética , Humanos , Imuno-Histoquímica , Lipocalina-2 , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Análise de Sequência com Séries de Oligonucleotídeos , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Análise Serial de Tecidos , Transcriptoma , Adulto Jovem
16.
Biol Reprod ; 93(4): 100, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26353891

RESUMO

The dysregulation of endometrial immune response to bacterial lipopolysaccharide (LPS) has been implicated in uterine disease and infertility in the postpartum dairy cow, although the mechanisms are not clear. Here, we investigated whole-transcriptomic gene expression in primary cultures of mixed bovine epithelial and stromal endometrial cells. Cultures were exposed to LPS for 6 h, and cellular response was measured by bovine microarray. Approximately 30% of the 1006 genes altered by LPS were classified as being involved in immune response. Cytokines and chemokines (IL1A, CX3CL1, CXCL2, and CCL5), interferon (IFN)-stimulated genes (RSAD2, MX2, OAS1, ISG15, and BST2), and the acute phase molecule SAA3 were the most up-regulated genes. Ingenuity Pathway Analysis identified up-regulation of many inflammatory cytokines and chemokines, which function to attract immune cells to the endometrium, together with vascular adhesion molecules and matrix metalloproteinases, which can facilitate immune cell migration from the tissue toward the uterine lumen. Increased expression of many IFN-signaling genes, immunoproteasomes, guanylate-binding proteins, and genes involved in the intracellular recognition of pathogens suggests important roles for these molecules in the innate defense against bacterial infections. Our findings confirmed the important role of endometrial cells in uterine innate immunity, whereas the global approach used identified several novel immune response pathways triggered by LPS in the endometrium. Additionally, many genes involved in endometrial response to the conceptus in early pregnancy were also altered by LPS, suggesting one mechanism whereby an ongoing response to infection may interfere with the establishment of pregnancy.


Assuntos
Endométrio/imunologia , Perfilação da Expressão Gênica , Imunidade Inata/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Proteínas de Fase Aguda/biossíntese , Proteínas de Fase Aguda/genética , Animais , Bovinos , Moléculas de Adesão Celular/biossíntese , Moléculas de Adesão Celular/genética , Sobrevivência Celular , Células Cultivadas , Quimiocinas/biossíntese , Quimiocinas/genética , Citocinas/biossíntese , Citocinas/genética , Endométrio/efeitos dos fármacos , Feminino , Redes Reguladoras de Genes/genética , Gravidez
17.
J Toxicol Environ Health A ; 78(12): 711-24, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26090557

RESUMO

Nanoparticles (NP) are pervasive in many areas of modern life, with little known about their potential toxicities. One commercially important NP is cadmium oxide (CdO), which is used to synthesize other Cd-containing NP, such as quantum dots. Cadmium (Cd) is a well-known nephrotoxicant, but the nephrotoxic potential of CdO NP remains unknown, particularly when exposure occurs during pregnancy. Therefore, pregnant CD-1 mice were used to examine the effects of inhaled CdO NP (230 µg CdO NP/m(3)) on maternal and neonatal renal function by examining urinary creatinine and urinary biomarkers of kidney injury, including kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL). Inhalation of CdO NP by dams produced a fivefold increase in urinary Kim-1 with no marked effect on urinary creatinine levels. Kim-1 mRNA expression peaked by gestational day (GD) 10.5, and NGAL expression increased from GD 10.5 to 17.5. In addition, histological analyses revealed proximal tubular pathology at GD 10.5. Neonatal Kim-1 mRNA expression rose between postnatal days (PND) 7 and 14, with mammary glands/milk being the apparent source of Cd for offspring. These studies demonstrate that, similar to what is seen with other Cd forms, Cd associated with inhaled CdO NP results in renal injury to both directly exposed dam and offspring. As commercial uses for nanotechnology continue to expand throughout the world, risks for unintentional exposure in the workplace increase. Given the large number of women in the industrial workforce, care needs to be taken to protect these already vulnerable populations.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/congênito , Compostos de Cádmio/toxicidade , Nanopartículas/toxicidade , Óxidos/toxicidade , Injúria Renal Aguda/patologia , Proteínas de Fase Aguda/biossíntese , Proteínas de Fase Aguda/genética , Animais , Animais Recém-Nascidos , Biomarcadores/urina , Compostos de Cádmio/farmacocinética , Creatinina/urina , Feminino , Glicosúria/induzido quimicamente , Glicosúria/urina , Receptor Celular 1 do Vírus da Hepatite A , Exposição por Inalação , Rim/patologia , Lipocalina-2 , Lipocalinas/biossíntese , Lipocalinas/genética , Glândulas Mamárias Animais/metabolismo , Exposição Materna , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Camundongos , Proteínas Oncogênicas/biossíntese , Proteínas Oncogênicas/genética , Óxidos/farmacocinética , Gravidez , RNA Mensageiro/biossíntese
18.
Dev Comp Immunol ; 53(1): 112-22, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26116443

RESUMO

The expression of genes encoding the acute phase proteins (APP) during the course of Trypanasoma carassii infection in the goldfish was determined using quantitative PCR. Significant changes in the mRNA levels of ceruloplasmin (Cp), C-reactive protein (CRP), transferrin (Tf), hemopexin (Hx) and serum amyloid A (SAA) were observed in the kidney, liver and spleen at various days post infection (dpi). Of the five acute phase protein genes examined, CRP and SAA exhibited the highest expression in the tissues during the acute infection. Cp and Tf were up-regulated throughout the acute course of infection in the liver. During the chronic phase of the infection, APP expression in the liver was similar to that in the non-infected control fish. At 7 dpi, Cp, Tf and Hx were down-regulated in the spleen, and Cp and Tf kidney, but their mRNA levels gradually returned to those of control non-infected fish. In contrast, during the chronic phase of the infection, there was an up-regulation of Cp, Hx and Tf in the spleen, and Tf and SAA in the kidney. The goldfish CRP was cloned and functionally characterized. CRP was differentially expressed in normal goldfish immune cells, with highest expression in monocytes and lowest expression in mature macrophages. A recombinant goldfish CRP (rgfCRP) was generated using prokaryotic expression. rgfCRP enhanced complement-mediated killing of trypanosomes in vitro, and the lysis increased after addition of immune serum. rgfCRP did not affect the production of reactive oxygen and nitrogen intermediates by monocytes and macrophages, respectively.


Assuntos
Proteínas de Fase Aguda/biossíntese , Reação de Fase Aguda/imunologia , Carpa Dourada/imunologia , Proteínas Recombinantes/farmacologia , Trypanosoma/imunologia , Proteínas de Fase Aguda/genética , Animais , Proteína C-Reativa/genética , Proteína C-Reativa/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/parasitologia , Carpa Dourada/parasitologia , Rim/imunologia , Fígado/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Baço/imunologia , Tripanossomíase/imunologia , Tripanossomíase/parasitologia
19.
Invest Ophthalmol Vis Sci ; 56(6): 3691-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26047170

RESUMO

PURPOSE: The current study was done to determine the role of lipocalin-2 (LCN2) in the pathogenesis of demyelinating optic neuritis using an experimental autoimmune optic neuritis (EAON) model. METHODS: The EAON was induced by subcutaneous immunization with an emulsified mixture of myelin oligodendrocyte glycoprotein (MOG35-55) peptide in mice. The LCN2 expression was examined in the optic nerve after MOG peptide injection. Degree of demyelination, inflammatory infiltration, glial activation, and expression profile of inflammatory mediators in the optic nerve were compared between LCN2 knockout (KO) animals and wild-type littermates by histological analysis and real-time PCR following EAON induction. Plasma levels of LCN2 in patients with optic neuritis were measured by ELISA. RESULTS: The expression of LCN2 was notably increased in the optic nerve after EAON induction. Expression of LCN2 was colocalized with reactive astrocytes. A significant reduction of demyelination, inflammatory infiltration, and gliosis was demonstrated in the optic nerve of LCN2 KO mice. The LCN2 KO mice also showed markedly reduced gene expression associated with the M1-polarized glia phenotype and toll-like receptor signaling in the optic nerve. The LCN2 levels in plasma were significantly higher in optic neuritis patients (71.6 ± 10.6 ng/mL) compared to healthy controls (37.4 ± 9.1 ng/mL, P = 0.0284). CONCLUSIONS: In this study, we demonstrated a significant induction of LCN2 expression in astrocytes of the optic nerve following EAON induction. Our results imply that astrocyte-derived LCN2 may have a pivotal role in the development of demyelinating optic neuritis, and LCN2 can be a therapeutic target to alleviate immune and inflammatory damage in the optic nerve.


Assuntos
Proteínas de Fase Aguda/fisiologia , Astrócitos , Doenças Desmielinizantes/etiologia , Lipocalinas/fisiologia , Neurite Óptica/etiologia , Proteínas Proto-Oncogênicas/fisiologia , Proteínas de Fase Aguda/biossíntese , Adulto , Animais , Astrócitos/metabolismo , Doenças Desmielinizantes/sangue , Feminino , Humanos , Lipocalina-2 , Lipocalinas/biossíntese , Lipocalinas/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurite Óptica/sangue , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/sangue
20.
Eur J Immunol ; 45(9): 2553-67, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26046550

RESUMO

Orally administrated iron is suspected to increase susceptibility to enteric infections among children in infection endemic regions. Here we investigated the effect of dietary iron on the pathology and local immune responses in intestinal infection models. Mice were held on iron-deficient, normal iron, or high iron diets and after 2 weeks they were orally challenged with the pathogen Citrobacter rodentium. Microbiome analysis by pyrosequencing revealed profound iron- and infection-induced shifts in microbiota composition. Fecal levels of the innate defensive molecules and markers of inflammation lipocalin-2 and calprotectin were not influenced by dietary iron intervention alone, but were markedly lower in mice on the iron-deficient diet after infection. Next, mice on the iron-deficient diet tended to gain more weight and to have a lower grade of colon pathology. Furthermore, survival of the nematode Caenorhabditis elegans infected with Salmonella enterica serovar Typhimurium was prolonged after iron deprivation. Together, these data show that iron limitation restricts disease pathology upon bacterial infection. However, our data also showed decreased intestinal inflammatory responses of mice fed on high iron diets. Thus additionally, our study indicates that the effects of iron on processes at the intestinal host-pathogen interface may highly depend on host iron status, immune status, and gut microbiota composition.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Infecções por Enterobacteriaceae/patologia , Mucosa Intestinal/patologia , Intestinos/patologia , Ferro da Dieta/administração & dosagem , Salmonelose Animal/metabolismo , Proteínas de Fase Aguda/biossíntese , Proteínas de Fase Aguda/imunologia , Animais , Peso Corporal/imunologia , Caenorhabditis elegans/imunologia , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/microbiologia , Citrobacter rodentium/imunologia , Dieta/métodos , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/metabolismo , Infecções por Enterobacteriaceae/microbiologia , Fezes/microbiologia , Feminino , Imunidade Inata , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Intestinos/imunologia , Intestinos/microbiologia , Ferro da Dieta/efeitos adversos , Complexo Antígeno L1 Leucocitário/biossíntese , Complexo Antígeno L1 Leucocitário/imunologia , Lipocalina-2 , Lipocalinas/biossíntese , Lipocalinas/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Oncogênicas/biossíntese , Proteínas Oncogênicas/imunologia , Salmonelose Animal/imunologia , Salmonelose Animal/microbiologia , Salmonelose Animal/mortalidade , Salmonella typhimurium/imunologia , Análise de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA