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1.
Zhonghua Yi Xue Za Zhi ; 99(48): 3808-3813, 2019 Dec 24.
Artigo em Chinês | MEDLINE | ID: mdl-31874519

RESUMO

Objective: To investigate the effect of silencing fatty acid binding protein 3 (FABP3) gene on lipopolysaccharide (LPS)-induced apoptosis and endoplasmic reticulum stress in alveolar epithelial cells A549. Methods: According to the processing method, A549 cells were divided into control group(A549 cells cultured for 24 h), LPS group (10 mg/L LPS treated A549 cells for 24 h), LPS+si-con group (10 mg/L LPS was used to treat A549 cells transfected with si-con for 24 h) and LPS+si-FABP3 group (10 mg/L LPS was used to treat A549 cells transfected with si-FABP3 for 24 h). Then quantitative real-time PCR was used to detect the level of FABP3, methylthiazoletrazolium was used to detect the cell proliferation, flow cytometry was used to detect the apoptosis, and Western Blot was used to detect the levels of FABP3, CyclinD1, cleaved-caspase-3, GRP78, ATF4, CHOP, cleaved-caspase-12 and p-Akt and PI3Kp110α protein expression. Enzyme-linked immunosorbent assay was used to detect the levels of IL-6, IL-8 and TNF-αlevels. Results: In the LPS group, FABP3 protein level (1.00±0.09) and mRNA (2.15±0.22), apoptosis rate [(26.1±2.6)%], inflammatory factor IL-6 [(554.4±55.4) ng/L], IL-8 [(389.3±38.5) ng/L] and TNF-α [(601.3±60.0) ng/L], cleaved-caspase-3 (1.00±0.11), GRP78 (1.05±0.11), ATF4 (1.20±0.12)), CHOP (1.05±0.10), cleaved-caspase-12 (1.10±0.11), p-Akt (0.88±0.08) and PI3Kp110α (0.75±0.08) protein levels were significantly higher than the control group [(0.53±0.05), (1.00±0.10), (4.5±0.5)%, (75.4±7.5) ng/L, (25.2±2.5) ng/L, (66.5±6.7) ng/L, (0.34±0.05), (0.35±0.05), (0.43±0.05), (0.37±0.04), (0.45±0.05), (0.16±0.04), (0.35±0.05)] (all P<0.05). Cell viability [(50.1±5.4)%] and CyclinD1 protein level (0.40±0.05) in LPS group were significantly lower than those in the control group [(100.1±12.4)%, (1.25±0.12)] (both P<0.05). Cell viability [(89.1±8.5)%] and CyclinD1 protein level (1.15±0.11) in LPS+si-FABP3 group were significantly higher than those in LPS+si-con group [(53.1±5.4)%, (0.42±0.05)] (both P<0.05). Apoptosis rate [(10.5±1.1)%], IL-6[(301.3±30.0) ng/L], IL-8[(189.4±19.0) ng/L], TNF-α [(400.1±40.1) ng/L], cleaved-caspase-3 (0.45±0.05), GRP78 (0.48±0.05), ATF4 (0.60±0.06), CHOP (0.55±0.05), cleaved-caspase-12 (0.60±0.06), p-Akt (0.50±0.05) and PI3Kp110α(0.45±0.05) in LPS+si-FABP3 group were significantly lower than those in LPS+si-con group [(28.1±2.8)%, (536.3±53.6) ng/L, (400.2±40.2) ng/L, (623.1±62.3) ng/L, (0.96±0.10), (1.02±0.10), (1.15±0.12), (1.10±0.11), (1.15±0.12), (0.90±0.09), (0.72±0.07)] (all P<0.05). Conclusion: Silencing FABP3 gene can inhibit LPS-induced alveolar epithelial cell apoptosis and endoplasmic reticulum stress, which may act by inhibiting the PI3K/Akt signaling pathway.


Assuntos
Células Epiteliais Alveolares , Estresse do Retículo Endoplasmático , Células A549 , Apoptose , Proteína 3 Ligante de Ácido Graxo , Humanos , Lipopolissacarídeos , Fosfatidilinositol 3-Quinases
2.
Int J Mol Sci ; 20(15)2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31344835

RESUMO

Post-traumatic stress disorder (PTSD) is characterized by an exaggerated response to contextual memory and impaired fear extinction, with or without mild cognitive impairment, learning deficits, and nightmares. PTSD is often developed by traumatic events, such as war, terrorist attack, natural calamities, etc. Clinical and animal studies suggest that aberrant susceptibility of emotion- and fear-related neurocircuits, including the amygdala, prefrontal cortex (PFC), and hippocampus may contribute to the development and retention of PTSD symptoms. Psychological and pharmacological therapy, such as cognitive behavioral therapy (CBT), and treatment with anti-depressive agents and/or antipsychotics significantly attenuate PTSD symptoms. However, more effective therapeutics are required for improvement of quality of life in PTSD patients. Previous studies have reported that ω3 long-chain polyunsaturated fatty acid (LCPUFA) supplements can suppress the development of PTSD symptoms. Fatty acid binding proteins (FABPs) are essential for LCPUFA intracellular trafficking. In this review, we have introduced Fabp3 null mice as an animal model of PTSD with impaired fear extinction. Moreover, we have addressed the neuronal circuits and novel therapeutic strategies for PTSD symptoms.


Assuntos
Proteína 3 Ligante de Ácido Graxo/genética , Neurônios/metabolismo , Transtornos de Estresse Pós-Traumáticos/genética , Animais , Antidepressivos/uso terapêutico , Emoções/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Humanos , Camundongos , Camundongos Knockout , Neurônios/patologia , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Transtornos de Estresse Pós-Traumáticos/patologia
3.
Gene ; 710: 156-160, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31173805

RESUMO

Heart fatty acid-binding protein (H-FABP) belongs to a family of intracellular fatty acid-binding proteins that are involved in the transport of long-chain fatty acids. Previous studies have indicated that H-FABP is significantly associated with intramuscular fat (IMF) content in pig. In this study, we compared the mRNA and protein expression of H-FABP between Tibetan pig (with high IMF) and Large White pig (with low IMF). The expression of H-FABP at both mRNA and protein levels in the tissues of backfat, longissimus dorsi muscle and liver was found to be significantly higher in TP than in LW. Single-nucleotide polymorphisms (SNPs) in a 2 kb region upstream of the start codon of the gene were screened using Sanger sequencing. We accordingly identified three SNPs (C-1375G, C-314T and T-158G) between the TP and LW populations and genotyped these based on PCR-restriction fragment length polymorphisms (PCF-RFLPs) analysis. The results showed that the C-1375G site might regulate H-FABP gene expression and thus be associated with fat deposition in pigs. Our study provides important data for further investigating the regulatory mechanism of H-FABP for fat deposition in pigs.


Assuntos
Músculos do Dorso/metabolismo , Proteína 3 Ligante de Ácido Graxo/genética , Proteína 3 Ligante de Ácido Graxo/metabolismo , Gordura Intra-Abdominal/metabolismo , Fígado/metabolismo , Polimorfismo de Nucleotídeo Único , Animais , Códon de Iniciação , Perfilação da Expressão Gênica , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNA , Especificidade da Espécie , Suínos , Distribuição Tecidual
4.
Neuropharmacology ; 150: 164-174, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30930168

RESUMO

Accumulation and aggregation of α-synuclein (αSyn) triggers dopaminergic (DAergic) neuronal loss in Parkinson's disease (PD). This pathological event is partly facilitated by the presence of long-chain polyunsaturated fatty acids (LC-PUFAs), including arachidonic acid. The intracellular transport and metabolism of LC-PUFAs are mediated by fatty acid-binding proteins (FABPs). We previously reported that heart-type FABP (FABP3) interacts with αSyn, thereby promoting αSyn oligomerization in DAergic neurons in the substantia nigra pars compacta (SNpc) following 1-methyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. This αSyn oligomerization is prevented in Fabp3 gene knock out mice. We document a novel FABP3 ligand, MF1 (4-(2-(1-(2-chlorophenyl)-5-phenyl-1H-pyrazol-3-yl)phenoxy)butanoic acid), that inhibits αSyn accumulation in DA neurons, thereby inhibiting the oligomerization of αSyn, loss of DAergic neurons, and PD-like motor deficits in MPTP-treated mice. Chronic oral administration of MF1 (0.3 or 1.0 mg/kg/day) significantly improved motor impairments and inhibited MPTP-induced accumulation and oligomerization of αSyn in the SNpc, and in turn prevented loss of tyrosine hydroxylase (TH)-positive cells in the SNpc. MF1 administration (0.1, 0.3, or 1.0 mg/kg/day) also restored MPTP-induced cognitive impairments. Although chronic administration of l-DOPA (3,4-dihydroxl-l-phenylalanine; 25 mg/kg/day, i.p.) also improved motor deficits, it failed to improve the cognitive impairments. In addition, l-DOPA failed to inhibit DAergic neuronal loss and αSyn pathologies in the SNpc. In summary, the novel FABP3 ligand MF1 rescues MPTP-induced behavioural and neuropathological features, suggesting that MF1 may be a disease-modifying drug candidate for synucleinopathies.


Assuntos
Neurônios Dopaminérgicos/metabolismo , Proteína 3 Ligante de Ácido Graxo/agonistas , Intoxicação por MPTP/metabolismo , Destreza Motora/efeitos dos fármacos , alfa-Sinucleína/metabolismo , Animais , Neurônios Dopaminérgicos/patologia , Proteína 3 Ligante de Ácido Graxo/efeitos dos fármacos , Intoxicação por MPTP/patologia , Masculino , Camundongos
5.
Iran J Kidney Dis ; 13(2): 120-128, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30988249

RESUMO

INTRODUCTION: Myocardial dysfunction is a leading cause of mortality in chronic kidney disease (CKD) children specially those on regular hemodialysis. Cardiac biomarkers play a key role for early detection of myocardial injury. We aim to clarify the prognostic role of circulating cardiac biomarkers, heart type fatty acid binding protein (H-FABP) and pregnancy associated plasma protein-A (PAPP-A) in CKD children on regular hemodialysis. MATERIAL AND METHODS: This is a prospective case control study over 2 years duration. Initial assessment included 20 CKD children on regular hemodialysis and 20 age- and sex- matched healthy children as a control group. Serum level of H-FABP and PAPP-A were measured and correlated to conventional echocardiographic findings and cardiovascular outcome in CKD children. RESULTS: 60% of CKD children developed cardiovascular comorbidities. H-FABP and PAPP-A levels were significantly elevated especially in those with worse cardiovascular outcome. H-FABP and PASP-A levels were positively correlated with LVM index. At cut off point > 17.65 pg/mL, H-FABP has 91% sensitivity and 87.5% specificity for prediction of cardiac morbidity. Elevated H-FABP (OR = 33; CI 95%: 2.455 - 443.591), LVM indexed to body surface area (OR = 21; CI 95%: 1.777 - 248.103), LVM indexed to lean body mass (OR = 15; CI 95%: 1.652 -136.172), elevated PAPP-A (OR = 9.8; CI 95%: 0.898 - 106.845) and Hypertension (OR = 8.333; CI 95%: 1.034 - 67.142) are the main risk factors for cardiac morbidities in CKD children. CONCLUSIONS: Elevated H-FABP and PAPP-A are valuable prognostic markers for cardiovascular outcome in CKD children on regular hemodialysis.


Assuntos
Doenças Cardiovasculares/etiologia , Proteína 3 Ligante de Ácido Graxo/sangue , Proteína Plasmática A Associada à Gravidez/análise , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Adolescente , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Ecocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertensão/complicações , Masculino , Prognóstico , Estudos Prospectivos , Diálise Renal , Insuficiência Renal Crônica/sangue , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade
6.
Vet J ; 244: 16-22, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30825889

RESUMO

The study objective was to investigate heart-fatty acid binding protein (HFABP) concentrations in dogs with degenerative valvular disease (MVD) and dilated cardiomyopathy (DCM), and its potential as a prognostic factor. Plasma HFABP, N-terminal pro brain natriuretic peptide (NTproBNP) and serum cardiac troponin I (cTnI) levels were measured in 21 control dogs, 23 dogs with MVD and 13 dogs with DCM, with repeated sampling at 1 and 3 months after initial presentation. All dogs were followed up after 6 and 12 months to verify survival. Heart-fatty acid binding protein concentrations were significantly higher in dogs with MVD and DCM than controls at initial presentation, and after 1 month in dogs with MVD. For dogs with DCM, a significant reduction in HFABP levels over time was observed. Comparing ACVIM stages, highest HFABP concentrations were detected in ACVIM stage C dogs compared to stage B, with the lowest levels seen in controls, and a reduction over time in stage C dogs was present. Similarly, cTnI concentrations were higher in DCM and stage C in comparison to control dogs and reduced over time, while NTproBNP concentrations were only higher in diseased dogs at 1 month. Heart-fatty acid binding protein and cTnI levels at initial presentation and ACVIM disease stage were independent predictors of survival in a univariate analysis. The elevation of HFABP in dogs with MVD and DCM in comparison to controls, its association with disease severity, and its potential in predicting reduced survival, suggest that HFABP might be useful as marker for canine MVD and DCM.


Assuntos
Biomarcadores/metabolismo , Cardiomiopatia Dilatada/veterinária , Doenças do Cão/metabolismo , Proteína 3 Ligante de Ácido Graxo/metabolismo , Doenças das Valvas Cardíacas/veterinária , Animais , Biomarcadores/sangue , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/metabolismo , Estudos de Casos e Controles , Doenças do Cão/sangue , Cães , Proteína 3 Ligante de Ácido Graxo/sangue , Feminino , Doenças das Valvas Cardíacas/sangue , Doenças das Valvas Cardíacas/metabolismo , Masculino , Peptídeo Natriurético Encefálico/sangue , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/metabolismo , Valor Preditivo dos Testes , Troponina I/sangue , Troponina I/metabolismo
7.
Bratisl Lek Listy ; 120(2): 124-130, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30793616

RESUMO

OBJECTIVES: We aimed to compare the plasma levels of biomarkers such as: serum Gal-3, H-FABP, cTnI, and CK-MB in patients, who were admitted to the emergency room with chest pain, and to determine whether these biomarkers have early diagnostic value of acute coronary syndrome (ACS). METHODS: The study was performed in 60 patients aged ≥ 18 years, who were admitted to emergency room. These patients were divided into 3 groups: patients with STEMI (group I, n = 20), patients with NSTEMI (group II, n = 20), and patients with USAP (group III, n = 20). Serum Gal-3, H-FABP, cTnI, and CK-MB levels were measured at admission, and at the 2nd and 4th hours. RESULTS: There were statistically significant differences between the groups in terms of Gal-3 levels at admission, and the 2nd and 4th hours (p = 0.007, p = 0.002, and p = 0.001, respectively). There were statistically significant differences between the groups in terms of H-FABP levels at admission, and the 2nd and 4th hours (p = 0.001, p = 0.003, and p = 0.003, respectively).There were statistically significant differences between the groups in terms of cTnI levels at admission, and the 2nd and 4th hours (p < 0.001, p < 0.001, and p < 0.001, respectively). CONCLUSIONS: According to the results of the study, cTnI, H-FABP, and Gal-3 are useful parameters that can be used in the early diagnosis of ACS (Tab. 4, Ref. 36).


Assuntos
Síndrome Coronariana Aguda , Biomarcadores , Proteína 3 Ligante de Ácido Graxo , Fatores de Transcrição , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Diagnóstico Precoce , Proteína 3 Ligante de Ácido Graxo/sangue , Proteínas de Ligação a Ácido Graxo , Humanos , Sensibilidade e Especificidade , Fatores de Transcrição/sangue , Troponina I
8.
ESC Heart Fail ; 6(2): 416-427, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30801997

RESUMO

AIMS: The importance of true worsening renal failure (WRF), which is associated with a poor prognosis, had been suggested in patients with acute heart failure (AHF). The aim of the present study was to establish the biomarker strategy for the prediction of true WRF in AHF. METHODS AND RESULTS: Two hundred eighty-one patients with AHF were analysed. Their biomarkers were measured within 30 min of admission. Patients were assigned to the non-WRF (n = 168), pseudo-WRF (n = 56), or true-WRF (n = 57) groups using the criteria of both acute kidney injury on admission and increasing serum creatinine value during the first 7 days. A Kaplan-Meier curve showed that the survival and heart failure event rate of the true-WRF group within 1000 days was significantly lower than that of the non-WRF and pseudo-WRF groups (P ≤ 0.001). The multivariate Cox regression model also indicated that true WRF was an independent predictor of 1000 day mortality and heart failure events [hazard ratio: 4.315, 95% confidence interval (CI): 2.466-7.550, P ≤ 0.001, and hazard ratio: 2.834, 95% CI: 1.893-4.243, P ≤ 0.001, respectively]. The serum heart-type fatty acid-binding protein (s-HFABP) levels were significantly higher in the true-WRF group than in the non-WRF and pseudo-WRF groups (P ≤ 0.001). The multivariate logistic regression model indicated that the predictive biomarker for the true-WRF group was the s-HFABP level (odds ratio: 5.472, 95% CI: 2.729-10.972, P ≤ 0.001). The sensitivity and specificity for indicating the presence of true WRF were 73.7% and 76.8% (area under the curve = 0.831) for s-HFABP in whole patients, respectively, and 94.7% and 72.7% (area under the curve = 0.904) in non-chronic kidney disease (CKD) patients, respectively. CONCLUSIONS: Cardiac biomarkers, especially the s-HFABP, might predict the development of true WRF in AHF patients. Furthermore, the predictive value was higher in AHF patients without CKD than in those with CKD.


Assuntos
Lesão Renal Aguda/etiologia , Creatinina/metabolismo , Proteína 3 Ligante de Ácido Graxo/metabolismo , Insuficiência Cardíaca/complicações , Lipocalina-2/metabolismo , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores/urina , Progressão da Doença , Feminino , Seguimentos , Taxa de Filtração Glomerular , Insuficiência Cardíaca/metabolismo , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Tempo
9.
Eur J Appl Physiol ; 119(2): 455-464, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30499054

RESUMO

PURPOSE: The tensiomyography (TMG) technique is increasingly used to determine muscle contractile properties in exercise and injury management. The present study investigated the informative value of TMG parameters in correlation with commonly used (creatine kinase, CK; myoglobin, Mb) and novel candidate biomarkers of muscle damage (heart-type fatty acid-binding protein, h-FABP; high-mobility group box 1, HMGB1). METHODS: Ten untrained men performed 6 × 10 eccentric contractions of the elbow flexors at 110% of the concentric one repetition maximum. CK, Mb, h-FABP, HMGB1, arm circumference, pain and TMG data, including maximal displacement (Dm) and temporal outcomes as the contraction time (Tc), sustained time (Ts), delay time (Td), and relaxation time (Tr), were assessed pre-exercise, post-exercise, 20 min, 2 h and on the consecutive 3 days post-exercise. RESULTS: CK and h-FABP significantly increased beginning at 24 h, Mb already increased at 2 h (p < 0.05). HMGB1 was only increased immediately post-exercise (p = 0.02). Tc and Td remained unchanged, whereas Ts and Tr were significantly slower beginning at 24 h (p < 0.05). Dm was decreased within the first 24 h and after 72 h (p < 0.01). The % change from pre-exercise correlated for Dm with CK, Mb, and h-FABP the highest at 48 h (r = - 0.95, - 0.87 and - 0.79; p < 0.01) and for h-FABP with CK and Mb the highest at 24 h (r = 0.96 and 0.94, for all p < 0.001). CONCLUSION: This study supports the correlation of TMG parameters with muscle damage markers after eccentric exercise. Therefore, TMG could represent a non-invasive and cost effective alternative to quantify the degree of muscle damage after exercise interventions.


Assuntos
Articulação do Cotovelo/fisiologia , Proteína 3 Ligante de Ácido Graxo/sangue , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Adulto , Biomarcadores/sangue , Creatina Quinase/sangue , Cotovelo/fisiologia , Proteína HMGB1/sangue , Humanos , Masculino , Mioglobina/sangue , Miografia , Adulto Jovem
10.
Aging Clin Exp Res ; 31(9): 1207-1217, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30456501

RESUMO

BACKGROUND: Our previous research has shown American Society of Anaesthesiologists physical status classification (ASA) score and Americal College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) calculator to have the most accuracy in the prediction of postoperative mortality. AIMS: The aim of our research was to define the most reliable combination of cardiac biomarkers with ASA and ACS NSQIP. METHODS: We have included a total of 78 patients. ASA score has been determined in standard fashion, while we used the available interactive calculator for the ACS NSQIP score. Biomarkers BIRC5, H-FABP, and hsCRP have been measured in specialized laboratories. RESULTS: All of the deceased patients had survivin (BIRC5) > 4.00 pg/ml, higher values of H-FABP and hsCRP and higher estimated levels of ASA and ACS NSQIP (P = 0.0001). ASA and ACS NSQIP alone had AUC of, respectively, 0.669 and 0.813. The combination of ASA and ACS NSQIP had AUC = 0.841. Combination of hsCRP with the two risk scores had AUC = 0.926 (95% CI 0.853-1.000, P < 0.0001). If we add three cardiac biomarkers to this model, we get AUC as high as 0.941 (95% CI 0.876-1.000, P < 0.0001). The correction of statistical models with comorbidities (CIRS-G score) did not change the accuracy of prediction models that we have provided. DISCUSSION: Addition of ACS NSQIP and biomarkers adds to the accuracy of ASA score, which has already been proved by other authors. CONCLUSION: Cardiac biomarker hsCRP can be used as the most reliable cardiac biomarker; however, the "multimarker approach" adds the most to the accuracy of the combination of clinical risk scores.


Assuntos
Proteína C-Reativa/análise , Complicações Pós-Operatórias/mortalidade , Medição de Risco/métodos , Survivina/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Comorbidade , Proteína 3 Ligante de Ácido Graxo/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Melhoria de Qualidade , Curva ROC , Estados Unidos
11.
Anim Sci J ; 90(2): 214-221, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30556368

RESUMO

The aim of this study was to determine the effects of isonitrogenous and isocaloric diets containing different qualities of forages and concentrate content on milk fat composition and genes that encode mammary lipogenic enzymes in dairy cows. A total of 20 Holstein cows were assigned to 1 of 2 treatment diets composed of either mixed forages (MF, starch : 21.50%) or corn stover forage (CS, starch : 25.39%). Mammary tissue biopsies were performed to analyze the mRNA expression of lipogenic enzymes. Dry matter intake, body weight, milk protein, and lactose were not affected by treatments. The milk yield, fat content and saturated fatty acid (SFA) and short- and medium-chain fatty acid (SMFA) contents in milk were lower in the CS diet than in the MF diet, but the unsaturated FA and long-chain FA contents were higher. Genes involved in de novo FA synthesis, FA uptake and transport, and Δ9-desaturation were lower in the CS treatment than in the MF treatment. No effects on the nuclear transcription factors were observed between the two treatments. The data indicated that corn stover diet reduced the milk yield, fat content, SMFA, and SFA contents in milk, as well as the gene expression of mammary lipogenic enzymes in dairy cows.


Assuntos
Ração Animal , Bovinos/metabolismo , Bovinos/fisiologia , Dieta/veterinária , Ácidos Graxos/metabolismo , Lactação , Lipogênese/genética , Glândulas Mamárias Humanas/enzimologia , Glândulas Mamárias Humanas/metabolismo , Leite/metabolismo , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Ração Animal/análise , Animais , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismo , Proteína 3 Ligante de Ácido Graxo/genética , Proteína 3 Ligante de Ácido Graxo/metabolismo , Ácidos Graxos/biossíntese , Feminino , Expressão Gênica , Humanos , Lipase Lipoproteica/genética , Lipase Lipoproteica/metabolismo , Proteínas do Leite/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Amido , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Zea mays
12.
Lipids ; 53(10): 947-960, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30592062

RESUMO

Proteins involved in lipid homeostasis are often regulated through the nuclear peroxisome proliferator-activated receptors (PPAR). PPARα is the target for the fibrate-class of drugs. Fenofibrate has been approved for its lipid-lowering effects in patients with hypercholesterolemia and hypertriglyceridemia. We were interested in understanding the expression of the energy transporters in energy-utilizing tissues like liver, heart, muscle, and adipose tissues in rat with the hypothesis that the change in transporter expression would align with the known lipid-lowering effects of PPARα agonists like fenofibrate. We found that several fatty-acid transporter proteins had significantly altered levels following 8 days of fenofibrate dosing. The mRNA levels of the highly abundant Fatp2 and Fatp5 in rat liver increased approximately twofold and decreased fourfold, respectively. Several fatty-acid-binding proteins and acyl-CoA-binding proteins had a significant increase in mRNA abundance but not the major liver fatty-acid-binding protein, Fabp1. Of particular interest was the increased liver expression of Fabp3 also known as heart-fatty acid binding protein (H-FABP or FABP3). FABP3 has been proposed as a circulating clinical biomarker for cardiomyopathy and muscle toxicity, as well as a preclinical marker for PPARα-induced muscle toxicity. Here, we show that fenofibrate induces liver mRNA levels of Fabp3 ~5000-fold resulting in an approximately 50-fold increase in FABP3 protein levels in the whole liver. This increased liver expression complicates the interpretation and potential use of FABP3 as a specific biomarker for PPARα-induced muscle toxicities.


Assuntos
Biomarcadores Farmacológicos/análise , Biomarcadores Farmacológicos/sangue , Proteína 3 Ligante de Ácido Graxo/análise , Proteína 3 Ligante de Ácido Graxo/sangue , Fenofibrato/efeitos adversos , Hipolipemiantes/efeitos adversos , Fígado/efeitos dos fármacos , Animais , Biomarcadores Farmacológicos/metabolismo , Proteína 3 Ligante de Ácido Graxo/genética , Fenofibrato/toxicidade , Coração/efeitos dos fármacos , Hipolipemiantes/toxicidade , Fígado/metabolismo , Fígado/patologia , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
13.
J Neurosci ; 38(49): 10411-10423, 2018 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-30341178

RESUMO

Polyunsaturated fatty acids (PUFAs) are essential for brain development and function. Increasing evidence has shown that an imbalance of PUFAs is associated with various human psychiatric disorders, including autism and schizophrenia. Fatty acid-binding proteins (FABPs), cellular chaperones of PUFAs, are involved in PUFA intracellular trafficking, signal transduction, and gene transcription. In this study, we show that FABP3 is strongly expressed in the GABAergic inhibitory interneurons of the male mouse anterior cingulate cortex (ACC), which is a component of the limbic cortex and is important for the coordination of cognitive and emotional behaviors. Interestingly, Fabp3 KO male mice show an increase in the expression of the gene encoding the GABA-synthesizing enzyme glutamic acid decarboxylase 67 (Gad67) in the ACC. In the ACC of Fabp3 KO mice, Gad67 promoter methylation and the binding of methyl-CpG binding protein 2 (MeCP2) and histone deacetylase 1 (HDAC1) to the Gad67 promoter are significantly decreased compared with those in WT mice. The abnormal cognitive and emotional behaviors of Fabp3 KO mice are restored by methionine administration. Notably, methionine administration normalizes Gad67 promoter methylation and its mRNA expression in the ACC of Fabp3 KO mice. These findings demonstrate that FABP3 is involved in the control of DNA methylation of the Gad67 promoter and activation of GABAergic neurons in the ACC, thus suggesting the importance of PUFA homeostasis in the ACC for cognitive and emotional behaviors.SIGNIFICANCE STATEMENT The ACC is important for emotional and cognitive processing. However, the mechanisms underlying its involvement in the control of behavioral responses are largely unknown. We show the following new observations: (1) FABP3, a PUFA cellular chaperone, is exclusively expressed in GABAergic interneurons in the ACC; (2) an increase in Gad67 expression is detected in the ACC of Fabp3 KO mice; (3) the Gad67 promoter is hypomethylated and the binding of transcriptional repressor complexes is decreased in the ACC of Fabp3 KO mice; and (4) elevated Gad67 expression and abnormal behaviors seen in Fabp3 KO mice are mostly recovered by methionine treatment. These suggest that FABP3 regulates GABA synthesis through transcriptional regulation of Gad67 in the ACC.


Assuntos
Metilação de DNA/fisiologia , Proteína 3 Ligante de Ácido Graxo/biossíntese , Glutamato Descarboxilase/metabolismo , Giro do Cíngulo/metabolismo , Regiões Promotoras Genéticas/fisiologia , Animais , Linhagem Celular Tumoral , Proteína 3 Ligante de Ácido Graxo/genética , Glutamato Descarboxilase/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Técnicas de Cultura de Órgãos
14.
Mol Biol Rep ; 45(6): 1575-1585, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30288642

RESUMO

This study was designed to screen the crossbred pigs for SNPs in five candidate genes, associated with pork quality traits and to differentiate their genotypes by PCR-RFLP. The results indicated that genotypes of crossbred pigs were NN (90%) and Nn (10%) for RYR1; RR (83%) and QR (17%) for PRKAG3; HH (98%), Hh (1%) and hh (1%) for HFABP; DD (99%) and CD (1%) for MYF-5; and AG (57%), GG (26%) and AA (17%) for MC4R SNPs, respectively. Allelic frequencies for five SNPs {RYR1 (1843C>T), PRKAG3 (c.599G>A), HFABP (c.1322C>T), MYF-5 (c.1205A>C) and MC4R (c.1426A>G)} were 0.95 and 0.05 (N/n), 0.08 and 0.92 (Q/R), 0.99 and 0.01 (H/h), 0.00 and 1.00 (C/D) and 0.45 and 0.55 (A/G), respectively. The effect of RYR1 (1843C>T) SNP was significant on pH45 (P < 0.05), pH24 (P < 0.05) and protein % (P < 0.05). The PRKAG3 (c.599G>A) and MC4R (c.1426A>G) SNP had significant association with dressing percentages. The results revealed that RYR1, PRKAG3 and MC4R SNPs may be used in marker associated selection for pork quality traits in crossbred pigs.


Assuntos
Carne Vermelha/análise , Sus scrofa/genética , Proteínas Quinases Ativadas por AMP/genética , Alelos , Criação de Animais Domésticos/métodos , Animais , Cruzamento , Proteína 3 Ligante de Ácido Graxo/genética , Qualidade dos Alimentos , Frequência do Gene/genética , Estudos de Associação Genética , Genótipo , Haplótipos , Índia , Desequilíbrio de Ligação , Carne/análise , Melanocortinas/genética , Fator Regulador Miogênico 5/genética , Fenótipo , Polimorfismo Genético/genética , Locos de Características Quantitativas , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Suínos/genética
15.
Nihon Yakurigaku Zasshi ; 152(4): 194-201, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30298841

RESUMO

Posttraumatic stress disorder (PTSD) is most often induced by traumatic events and serious public health problems. PTSD is characterized by excessive response to contextual memory and impaired fear extinction and also associated with mild cognitive impairment, attention and learning deficits. Clinical and animal studies suggest that increased susceptibility of emotion- and fear-related neuronal circuits, including those in the amygdala, prefrontal cortex and hippocampus, contributes to development and retention of PTSD symptoms. However, mechanisms underlying this susceptibility to fear are not known and the useful therapeutic approaches are limited. Recently, there have been reports that ω3 LCPUFA supplementation can prevent development of PTSD and significantly ameliorate symptoms in patients with PTSD after accidental injury such as motor vehicle accidents and natural calamities. Importantly, Fabp7 null mice exhibit enhancement of fear memory consolidation and anxiety-related behaviors that resemble PTSD-like behaviors in humans. In this review, we focused behavioral phenotype of PTSD in Fabp3 null mice. The Fabp3 null mice exhibit cognitive deficits, hyperlocomotion and impaired fear extinction, and thus show PTSD-like behaviors. Chronic administration of ramelteon, a melatonin receptor agonist, improved all PTSD-like behaviors tested in Fabp3-/- mice. Relevant to mechanisms underlying impaired fear extinction, we observed that Ca2+/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation increases in the basolateral amygdala (BLA) but remained unchanges in the hippocampus of Fabp3-/- mice. Likewise, the number of c-Fos positive neurons in BLA significantly increased after exposure to contextual fear conditions. Finally, chronic ramelteon administration restored abnormal c-Fos expression and CaMKII autophosphorylation in the BLA of Fabp3-/- mice. Taken together, Fabp3-/- mice show PTSD-like behaviors, and ramelteon is an attractive candidate for PTSD therapeutics in human.


Assuntos
Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/terapia , Tonsila do Cerebelo/fisiopatologia , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína 3 Ligante de Ácido Graxo/genética , Medo , Hipocampo/fisiopatologia , Humanos , Camundongos , Camundongos Knockout , Córtex Pré-Frontal/fisiopatologia
16.
Sci Rep ; 8(1): 14410, 2018 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-30258183

RESUMO

To investigate the prognostic value of heart-type fatty acid binding protein (H-FABP) in patients with stable coronary heart disease (SCHD). A total of 1,071 patients with SCHD were prospectively enrolled in this Taiwan multicenter registry study, followed for 24 months. The cut-off value of H-FABP, 4.143 pg/mL, was determined using receiver operating characteristic curves. The primary cardiovascular (CV) outcome was composite CV events, defined as cardiovascular or cerebrovascular death, myocardial infarction (MI), stroke, angina related-hospitalization, PAOD-related hospitalization and heart failure. Secondary outcomes included CV or cerebrovascular death, nonfatal MI, nonfatal stroke, and acute heart failure-related hospitalization. We found that the high H-FABP group had more than a two-fold higher rate of primary CV outcomes than the low H-FABP group (32.36% vs. 15.78%, p < 0.001). Eleven patients (4.82%) of the high H-FABP group died during the 24 months of follow-up, compared to only one patient (0.12%) in the low H-FABP group. The acute heart failure-related hospitalization rate was also significantly higher in the high H-FABP group (3.5% vs. 0.95%, p < 0.005). The results remained significant after adjusting for baseline covariates. In conclusion, H-FABP was an independent predictor for CV outcomes in the patients with SCHD, mainly in CV death and acute heart failure-related hospitalization.


Assuntos
Doença das Coronárias/sangue , Doença das Coronárias/diagnóstico , Proteína 3 Ligante de Ácido Graxo/sangue , Adulto , Doença das Coronárias/epidemiologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Prognóstico , Estudos Prospectivos , Taiwan/epidemiologia , Adulto Jovem
17.
Dermatology ; 234(5-6): 173-179, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30176661

RESUMO

BACKGROUND: In psoriasis, a common immune-mediated disease affecting 2-3% of the population worldwide, there is an increased prevalence of extracutaneous diseases including obesity, the metabolic syndrome, and cardiovascular disease. This is believed to be linked to systemic inflammation. In previous studies, we have explored various markers in plasma and serum to characterize the ongoing systemic inflammation in psoriasis patients compared to controls. We have identified several markers that were altered in psoriasis patients, but which all were unresponsive to narrowband UVB (NB-UVB) treatment. OBJECTIVE: The objective of the study was to evaluate the effect of NB-UVB treatment on markers of cardiovascular risk and systemic inflammation in psoriasis. METHODS: The levels of 17 potential biomarkers with an association with cardiovascular risk were quantitated in plasma from 37 age- and gender-matched psoriasis patients and controls at baseline and in 21 psoriasis patients after 12 weeks of NB-UVB treatment to identify a systemic treatment response. RESULTS: We identified the mediators endocan-1, CXCL16, and sVEGFR1, which were systemically decreased in psoriasis at baseline, as well as FABP3, FABP4, and sIL-1R1, which showed normal baseline levels. After 10-12 weeks of NB-UVB treatment, endocan-1 and CXCL16 were restored to normal levels, while sVEGFR1, FABP3, FABP4, and sIL-1R1 showed a significant reduction. CONCLUSION: The current study expands the number of potential biomarkers in psoriasis by including a greater number and variety of mediators, approaching the systemic inflammation from additional vantage points, including soluble immune receptors and adipocyte contribution, to provide a more complete picture of the systemic inflammatory state in psoriasis.


Assuntos
Quimiocina CXCL16/sangue , Proteínas de Neoplasias/sangue , Proteoglicanas/sangue , Psoríase/sangue , Psoríase/radioterapia , Terapia Ultravioleta , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Estudos de Casos e Controles , Proteína 3 Ligante de Ácido Graxo/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Humanos , Receptores Tipo I de Interleucina-1/sangue , Terapia Ultravioleta/métodos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue
18.
Alzheimers Res Ther ; 10(1): 98, 2018 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-30253800

RESUMO

BACKGROUND: Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by neuropathologic changes involving beta-amyloid (Aß), tau, neuronal loss, and other associated biological events. While levels of cerebrospinal fluid (CSF) Aß and tau peptides have enhanced the antemortem detection of AD-specific changes, these two markers poorly reflect the severity of cognitive and functional deficits in people with altered Aß and tau levels. While multiple previous studies identified non-Aß, non-tau proteins as candidate neurodegenerative markers to inform the A/T/N biomarker scheme of AD, few have advanced beyond association with clinical AD diagnosis. Here we analyzed nine promising neurodegenerative markers in a three-centered cohort using independent assays to identify candidates most likely to complement Aß and tau in the A/T/N framework. METHODS: CSF samples from 125 subjects recruited at the three centers were exchanged such that each of the nine previously identified biomarkers can be measured at one of the three centers. Subjects were classified according to cognitive status and CSF AD biomarker profiles as having normal cognition and normal CSF (n = 31), normal cognition and CSF consistent with AD (n = 13), mild cognitive impairment and normal CSF (n = 13), mild cognitive impairment with CSF consistent with AD (n = 23), AD dementia (n = 32; CSF consistent with AD), and other non-AD dementia (n = 13; CSF not consistent with AD). RESULTS: Three biomarkers were identified to differ among the AD stages, including neurofilament light chain (NfL; p < 0.001), fatty acid binding protein 3 (Fabp3; p < 0.001), and interleukin (IL)-10 (p = 0.033). Increased NfL levels were most strongly associated with the dementia stage of AD, but increased Fabp3 levels were more sensitive to milder AD stages and correlated with both CSF tau markers. IL-10 levels did not correlate with tau biomarkers, but were associated with rates of longitudinal cognitive decline in mild cognitive impairment due to AD (p = 0.006). Prefreezing centrifugation did not influence measured CSF biomarker levels. CONCLUSION: CSF proteins associated with AD clinical stages and progression can complement Aß and tau markers to inform neurodegeneration. A validated panel inclusive of multiple biomarker features (etiology, stage, progression) can improve AD phenotyping along the A/T/N framework.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico , Idoso , Biomarcadores/líquido cefalorraquidiano , Estudos de Coortes , Progressão da Doença , Proteína 3 Ligante de Ácido Graxo/líquido cefalorraquidiano , Feminino , Humanos , Interleucina-10/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano
20.
PLoS One ; 13(7): e0200394, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29985933

RESUMO

Mild traumatic brain injury (mTBI) patients may have trauma-induced brain lesions detectable using CT scans. However, most patients will be CT-negative. There is thus a need for an additional tool to detect patients at risk. Single blood biomarkers, such as S100B and GFAP, have been widely studied in mTBI patients, but to date, none seems to perform well enough. In many different diseases, combining several biomarkers into panels has become increasingly interesting for diagnoses and to enhance classification performance. The present study evaluated 13 proteins individually-H-FABP, MMP-1, MMP-3, MMP-9, VCAM, ICAM, SAA, CRP, GSTP, NKDA, PRDX1, DJ-1 and IL-10-for their capacity to differentiate between patients with and without a brain lesion according to CT results. The best performing proteins were then compared and combined with the S100B and GFAP proteins into a CT-scan triage panel. Patients diagnosed with mTBI, with a Glasgow Coma Scale score of 15 and one additional clinical symptom were enrolled at three different European sites. A blood sample was collected at hospital admission, and a CT scan was performed. Patients were divided into two two-centre cohorts and further dichotomised into CT-positive and CT-negative groups for statistical analysis. Single markers and panels were evaluated using Cohort 1. Four proteins-H-FABP, IL-10, S100B and GFAP-showed significantly higher levels in CT-positive patients. The best-performing biomarker was H-FABP, with a specificity of 32% (95% CI 23-40) and sensitivity reaching 100%. The best-performing two-marker panel for Cohort 1, subsequently validated in Cohort 2, was a combination of H-FABP and GFAP, enhancing specificity to 46% (95% CI 36-55). When adding IL-10 to this panel, specificity reached 52% (95% CI 43-61) with 100% sensitivity. These results showed that proteins combined into panels could be used to efficiently classify CT-positive and CT-negative mTBI patients.


Assuntos
Concussão Encefálica/sangue , Concussão Encefálica/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Proteína 3 Ligante de Ácido Graxo/sangue , Proteína Glial Fibrilar Ácida/sangue , Tomografia Computadorizada por Raios X , Biomarcadores/sangue , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Humanos , Interleucina-10/sangue , Masculino , Pessoa de Meia-Idade , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Sensibilidade e Especificidade
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