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1.
Int Heart J ; 61(2): 301-307, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32224602

RESUMO

Pulmonary hypertension (PH) caused by left-sided heart disease (LHD-PH) is classified into 2 types: isolated post-capillary PH (Ipc-PH) and combined pre- and post-capillary PH (Cpc-PH). However, the impact of pulmonary vascular resistance (PVR) or diastolic pressure gradient (DPG) on the prognosis of LHD-PH has varied among previous studies. Thus, we verified the significance of PVR or DPG on the prognosis of LHD-PH in our series.We analyzed 243 consecutive LHD-PH patients. The patients were divided into 3 groups: Group A, patients with PVR ≤ 3 Wood unit (WU) and DPG < 7 mmHg; Group B, patients with either PVR > 3 WU or DPG ≥ 7 mmHg; and Group C, patients with PVR > 3 WU and DPG ≥ 7 mmHg.The Kaplan-Meier curve demonstrated that Group B had lower cardiac death-free survival compared with Group A, whereas no significant differences were observed when compared with Group C. In the Cox hazard model, DPG was not associated with cardiac death in the LHD-PH patients. However, only in the ischemic heart disease group, patients with DPG ≥ 7 mmHg had worse prognosis compared with those with normal DPG.The cardiac death-free rate of patients with either increased PVR or DPG was close to that of patients with both increased PVR and DPG. It seems reasonable to define Cpc-PH only by PVR in the new criteria. However, the significance of DPG in LHD-PH might be dependent on the underlying cause of LHD-PH.


Assuntos
Pressão Sanguínea/fisiologia , Diástole/fisiologia , Insuficiência Cardíaca/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Taxa de Sobrevida , Resistência Vascular/fisiologia , Adulto , Idoso , Cardiomiopatias/complicações , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/fisiopatologia , Morte , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/fisiopatologia , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/etiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia , Prognóstico , Modelos de Riscos Proporcionais
2.
Cancer Sci ; 111(3): 807-816, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31908105

RESUMO

Activation-induced cell death (AICD) mediated by the Fas/Fas ligand (FasL) system plays a key role in regulating immune response. Although normal natural killer (NK) cells use this system for their homeostasis, malignant NK cells seem to disrupt the process. Extranodal NK/T-cell lymphoma, nasal type (ENKL) is a rare but fatal disease, for which novel therapeutic targets need to be identified. We confirmed that ENKL-derived NK cell lines NK-YS and Hank1, and primary lymphoma cells expressed procaspase-8/FADD-like interleukin-1ß-converting enzyme (FLICE) modulator and cellular FLICE-inhibitory protein (c-FLIP), along with Fas and FasL. Compared with Fas-sensitive Jurkat cells, NK-YS and Hank1 showed resistance to Fas-mediated apoptosis in spite of the same expression levels of c-FLIP and the death-inducing signaling complex (DISC) formation. Unexpectedly, the long isoform of c-FLIP (c-FLIPL ) was coimmunoprecipitated with Fas predominantly in both ENKL-derived NK cell lines after Fas ligation. Indeed, c-FLIPL was more sufficiently recruited to the DISC in both ENKL-derived NK cell lines than in Jurkat cells after Fas ligation. Knockdown of c-FLIPL per se enhanced autonomous cell death and restored the sensitivity to Fas in both NK-YS and Hank1 cells. Although ENKL cells are primed for AICD, they constitutively express and efficiently utilize c-FLIPL , which prevents their Fas-mediated apoptosis. Our results show that c-FLIPL could be a promising therapeutic target against ENKL.


Assuntos
Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Células Matadoras Naturais/metabolismo , Linfoma/metabolismo , Receptor fas/metabolismo , Apoptose/fisiologia , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 8/metabolismo , Caspases/metabolismo , Morte Celular/fisiologia , Proteína Ligante Fas , Proteína de Domínio de Morte Associada a Fas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Células Jurkat , Isoformas de Proteínas/metabolismo , Transdução de Sinais/fisiologia
3.
Intern Med ; 59(2): 221-227, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31511490

RESUMO

Pulmonary hypertension and hereditary hemorrhagic telangiectasia (HHT) have an association mediated by activin A receptor type II-like 1 (ACVRL1) gene pathogenic variants. A 30-year-old woman was previously admitted to a hospital due to lung hemorrhage, and was diagnosed with pulmonary hypertension, but stopped follow-up visits. At 48 years of age, she was admitted to our hospital and was diagnosed with HHT. Genetic testing revealed an ACVRL1 pathogenic variant. After the initiation of pulmonary vasodilator treatment, the patient's mean pulmonary artery pressure started to decrease from 43 mmHg, declining to 37 mmHg when she was 58 years of age. This is the first report describing the 28-year follow-up of an HHT and pulmonary hypertension patient with an ACVRL1 mutation.

4.
Int Heart J ; 60(6): 1430-1434, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31735783

RESUMO

Pulmonary arterial hypertension is a fatal disease caused by pulmonary arterial vasoconstriction and organic stenosis due to the proliferation of pulmonary smooth muscle cells and endothelial cells. Endothelial dysfunction, including impaired nitric oxide (NO) bioavailability, plays a crucial role in the pathogenesis of pulmonary hypertension, and endothelial nitric oxide synthase (eNOS) is an important modulator of pulmonary vasodilatation. Although senescence marker protein (SMP) 30 is known as an anti-aging protein, the role of SMP30 in pulmonary vessels is still unclear. In this study, we examined the role of SMP30 in pulmonary vasculature using SMP30-deficient mice.We used female SMP30-deficient mice and wild-type littermate (WT) mice at the age of 12 to 18 weeks. The WT and SMP30-deficient mice were exposed to normoxia or hypoxia (10% oxygen for 4 weeks). In normoxia, the right ventricular systolic pressure (RVSP) was not different between the WT and SMP30-deficient mice, but in hypoxia, the RVSP was significantly higher in the SMP30-deficient mice compared to the WT mice (P < 0.05). The hypoxia-induced increases in right ventricular hypertrophy and medial smooth muscle area of the pulmonary artery were comparable between the WT and the SMP30-deficient mice. Western blotting showed that eNOS phosphorylation in lung tissue was reduced in the SMP30-deficient mice compared to the WT mice in normoxia. However, in hypoxic conditions, eNOS phosphorylation was reduced in both the WT and SMP30-deficient mice with no differences in Akt phosphorylation.Our study demonstrated that SMP30 is involved in the development of hypoxia-induced pulmonary hypertension by impairment of eNOS activity.


Assuntos
Proteínas de Ligação ao Cálcio/fisiologia , Hipertensão Pulmonar/etiologia , Hipóxia/complicações , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Animais , Modelos Animais de Doenças , Feminino , Hipertensão Pulmonar/metabolismo , Hipóxia/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo III/metabolismo
5.
Plants (Basel) ; 8(10)2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31575078

RESUMO

As reactive oxygen species (ROS) play critical roles in plants to determine cell fate in various physiological situations, there is keen interest in the biochemical processes of ROS signal transmission. Reactive carbonyl species (RCS), the ,-unsaturated aldehydes and ketones produced from lipid peroxides, due to their chemical property to covalently modify protein, can mediate ROS signals to proteins. Comprehensive carbonyl analysis in plants has revealed that more than a dozen different RCS, e.g., acrolein, 4-hydroxy-(E)-2-nonenal and malondialdehyde, are produced from various membranes, and some of them increase and modify proteins in response to oxidative stimuli. At early stages of response, specific subsets of proteins are selectively modified with RCS. The involvement of RCS in ROS signaling can be judged on three criteria: (1) A stimulus to increase the ROS level in plants leads to the enhancement of RCS levels. (2) Suppression of the increase of RCS by scavenging enzymes or chemicals diminishes the ROS-induced response. (3) Addition of RCS to plants evokes responses similar to those induced by ROS. On these criteria, the RCS action as damaging/signaling agents has been demonstrated for root injury, programmed cell death, senescence of siliques, stomata response to abscisic acid, and root response to auxin. RCS thus act as damage/signal mediators downstream of ROS in a variety of physiological situations. A current picture and perspectives of RCS research are presented in this article.

6.
JCI Insight ; 4(17)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31484823

RESUMO

Sustained therapeutic responses from traditional and next-generation antiandrogen therapies remain elusive in clinical practice due to inherent and/or acquired resistance resulting in persistent androgen receptor (AR) activity. Antisense oligonucleotides (ASO) have the ability to block target gene expression and associated protein products and provide an alternate treatment strategy for castration-resistant prostate cancer (CRPC). We demonstrate the efficacy and therapeutic potential of this approach with a Generation-2.5 ASO targeting the mouse AR in genetically engineered models of prostate cancer. Furthermore, reciprocal feedback between AR and PI3K/AKT signaling was circumvented using a combination approach of AR-ASO therapy with the potent pan-AKT inhibitor, AZD5363. This treatment strategy effectively improved treatment responses and prolonged survival in a clinically relevant mouse model of advanced CRPC. Thus, our data provide preclinical evidence to support a combination strategy of next-generation ASOs targeting AR in combination with AKT inhibition as a potentially beneficial treatment approach for CRPC.

7.
Int Heart J ; 60(5): 1147-1153, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31484872

RESUMO

Heart failure causes increased venous pressure, leading to liver dysfunction. The fibrosis-4 index is a simple index for liver fibrosis and has been reported to be useful for predicting prognosis in heart failure; however, its impact on patients with pulmonary hypertension due to left heart disease (PH-LHD) has not yet been fully elucidated.We enrolled consecutive 230 hospitalized patients who had been diagnosed as having PH-LHD. The fibrosis-4 index was calculated as follows: [aspartate transaminase (U/L) × age]/[alanine transaminase 1/2 (U/L) × platelet count (109/L) ]. We followed patients for all-cause mortality during the follow-up period (mean 1112 ± 822 days).The patients were divided into tertiles based on their fibrosis-4 index: the first tertile 0.335 to 1.381; the second tertile 1.391 to 2.311; and the third tertile 2.323 to 14.339. Compared with the first tertile, the third tertile had lower estimated glomerular filtration rates and hemoglobin levels. All-cause mortality was significantly higher in the third than in the first tertile. In a Cox proportional hazard model, the fibrosis-4 index was a predictor of all-cause mortality in PH-LHD patients (HR 1.212, 95% CI 1.099-1.337, P < 0.001).The fibrosis-4 index is associated with kidney function, anemia, and high mortality in PH-LHD patients.


Assuntos
Causas de Morte , Insuficiência Cardíaca/mortalidade , Hipertensão Pulmonar/mortalidade , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/patologia , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Fibrose/sangue , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Hospitais Universitários , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Análise de Sobrevida , Disfunção Ventricular Esquerda/sangue
9.
Intern Med ; 58(15): 2139-2144, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30996169

RESUMO

Objective Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease that leads to right-sided heart failure with electrocardiographic abnormalities. There are only a few reports about the effects of balloon pulmonary angioplasty for CTEPH on the electrocardiographic criteria of right ventricular hypertrophy. To determine the effect of balloon angioplasty on electrocardiography in patients with CTEPH. Methods We evaluated electrocardiograms in 19 patients (mean age, 64±10 years) who underwent balloon pulmonary angioplasty. Results We compared the hemodynamic parameters after balloon pulmonary angioplasty. The mean pulmonary artery pressure was decreased (p<0.001), and the cardiac index was increased (p=0.025) after balloon pulmonary angioplasty. The level of brain natriuretic peptide was decreased (p=0.001) after balloon pulmonary angioplasty (p<0.001). We applied 15 criteria for right ventricular hypertrophy to the patients, according to the American Heart Association recommendations of the electrocardiogram, after balloon pulmonary angioplasty. Among the criteria, the numbers of patients who met the criteria of deep S in V6 (p=0.005) and max R in V1, 2+max S in I, aVL-S in V1 (p=0.046) were significantly decreased after balloon pulmonary angioplasty. The mean numbers regarding the right ventricular hypertrophic criteria in each patient were significantly decreased after balloon pulmonary angioplasty (4.8±2.6 to 3.1±2.5, p=0.003). Conclusion In addition to improvement in hemodynamics, improvement in right ventricular hypertrophy was also observed using the electrocardiographic criteria in patients with CTEPH after balloon pulmonary angioplasty, suggesting that we should pay more attention to these changes.


Assuntos
Angioplastia com Balão/efeitos adversos , Eletrocardiografia/métodos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/cirurgia , Hipertrofia Ventricular Direita/fisiopatologia , Embolia Pulmonar/complicações , Embolia Pulmonar/cirurgia , Idoso , Feminino , Hemodinâmica/fisiologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade
10.
J Pineal Res ; 66(4): e12564, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30715754

RESUMO

BACKGROUND: Melatonin is a multifunctional indolamine and has a cardioprotective role in a variety of cardiovascular processes via antioxidant, anti-inflammatory, antihypertensive, antithrombotic, and antilipemic effects. It has been reported that lower levels of circulating melatonin are significantly associated with a higher risk of acute myocardial infarction (AMI) and later cardiac remodeling. However, levels of melatonin in patients with dilated cardiomyopathy (DCM) and associations between melatonin levels and cardiac function remain unclear. METHODS AND RESULTS: We measured and compared plasma levels of melatonin in 61 control subjects, 81 AMI patients, and 77 DCM patients. Plasma levels of melatonin were progressively decreased from 71.9 pg/mL in the control group to 52.6 pg/mL in the DCM group and 21.9 pg/mL in the AMI group. Next, we examined associations of melatonin levels with parameters of laboratory data, echocardiography, and right-heart catheterization. In the DCM patients, circulating melatonin showed significant correlations with both high-sensitivity troponin T (R = -0.422, P < 0.001) and cardiac output (R = 0.431, P = 0.003), but not with B-type natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), pulmonary artery wedge pressure, or pulmonary artery pressure. CONCLUSION: Patients with not only AMI but also DCM had lower circulating melatonin levels. Circulating melatonin levels appear to correlate with myocardial injury and cardiac output in DCM patients.


Assuntos
Cardiomiopatia Dilatada/sangue , Melatonina/sangue , Doença Aguda , Idoso , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Peptídeo Natriurético Encefálico/sangue , Troponina/sangue
11.
ESC Heart Fail ; 6(2): 291-296, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30681298

RESUMO

AIMS: It has been reported that circulating soluble neprilysin (sNEP), which catalyses the degradation of several vasodilator peptides such as natriuretic peptides, predicts prognosis in heart failure patients with reduced ejection fraction. Hypoxia-induced decrease in NEP expression in lungs has been reported. However, the associations between sNEP and haemodynamic parameters, as well as the prognostic impact of sNEP in pulmonary hypertension (PH), remain unclear. We aimed to clarify the relationships between sNEP and natriuretic peptide, haemodynamics (e.g. parameters of echocardiography and right heart catheter) or prognosis in PH patients. METHODS AND RESULTS: First, we examined the associations between sNEP levels and natriuretic peptide, echocardiography, or right heart catheter in PH patients (mean pulmonary artery pressure ≥ 25 mmHg and pulmonary artery wedge pressure ≤ 15 mm Hg on the basis of right heart catheterization, n = 79). Next, we followed up the patients for all-cause mortality. Laboratory data revealed no significant correlations between sNEP and B-type natriuretic peptide (R = 0.022, P = 0.872), N-terminal proBNP (R = -0.018, P = 0.872), and high-sensitivity troponin I (R = 0.206, P = 0.107). Regarding the parameters of echocardiography and right heart catheter, there were no significant correlations between sNEP and left ventricular ejection fraction (R = -0.036, P = 0.764), right ventricular fractional area change (R = -0.259, P = 0.064), tricuspid valve pressure gradient (R = -0.037, P = 0.767), and any of the right heart catheter parameters. In the Kaplan-Meier analysis (mean follow-up, 1284 days, log-rank P = 0.531), all-cause mortality rates were comparable between the higher NEP group (sNEP ≥ median levels of 1.45 ng/mL, n = 39) and the lower NEP group (sNEP < 1.45 ng/mL, n = 40). In the Cox proportional hazard analysis, sNEP was not a predictor of all-cause mortality (hazard ratio 0.902, 95% CI 0.674-1.207, P = 0.487) in PH patients. CONCLUSIONS: Circulating sNEP does not correlate with natriuretic peptide, haemodynamic parameters, or prognosis in patients with PH.


Assuntos
Ventrículos do Coração/fisiopatologia , Hipertensão Pulmonar/sangue , Neprilisina/sangue , Pressão Propulsora Pulmonar/fisiologia , Função Ventricular Direita/fisiologia , Biomarcadores/sangue , Cateterismo Cardíaco/métodos , Ecocardiografia , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/mortalidade , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Peptídeos Natriuréticos/sangue , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida/tendências
12.
Fukushima J Med Sci ; 65(3): 109-121, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31915324

RESUMO

An advanced glycation end products (AGE)/a receptor for AGE (RAGE) axis plays a central role in the pathogenesis of diabetic vascular remodeling. This study was conducted to clarify the role of RAGE in nondiabetic atherosclerosis. We used the aortic and coronary atherosclerotic lesions of Watanabe heritable hyperlipidemic (WHHL) rabbits prone to myocardial infarction (WHHLMI) at 1 to 14 months. Immunohistochemistry demonstrated the significant expression of RAGE as early as at 1 month with the stronger expression at 3 and 7 months, which was remarkably diminished at 14 months. RAGE expression was concordant with AGE accumulation. The major original sources of RAGE expression were macrophages and smooth muscle cells in addition to endothelial cells, and RAGE expression was distributed in the areas of phospholipid products, a component of oxidized LDL and nitrotyrosine. The concentrations of serum AGE did not alter significantly with aging. These findings suggested the expression of RAGE was induced by hyperlipidemia and oxidative stress independent of diabetes in WHHLMI rabbits. Additionally, our in vitro study showed that silencing of RAGE tended to attenuate oxidized-LDL-triggered PAI-1 expression in human cultured macrophages, as well as oxidized-LDL-induced tissue factor expression in peritoneal macrophages, suggesting a possible role of RAGE in prothrombogenic molecular regulation. In conclusion, the present study provides in vivo evidence that RAGE plays an integral role in the initiation and progression of nondiabetic atherosclerosis, suggesting that RAGE may be a novel target for treating not only diabetic but also nondiabetic vascular complications.


Assuntos
Aterosclerose/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Aterosclerose/etiologia , Aterosclerose/patologia , Modelos Animais de Doenças , Feminino , Técnicas de Silenciamento de Genes , Produtos Finais de Glicação Avançada/sangue , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Imuno-Histoquímica , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estresse Oxidativo , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Coelhos , Receptor para Produtos Finais de Glicação Avançada/deficiência , Receptor para Produtos Finais de Glicação Avançada/genética , Tirosina/análogos & derivados , Tirosina/metabolismo
13.
Proc Natl Acad Sci U S A ; 115(45): E10768-E10777, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30348775

RESUMO

Plant immune responses mediated by the hormone jasmonoyl-l-isoleucine (JA-Ile) are metabolically costly and often linked to reduced growth. Although it is known that JA-Ile activates defense responses by triggering the degradation of JASMONATE ZIM DOMAIN (JAZ) transcriptional repressor proteins, expansion of the JAZ gene family in vascular plants has hampered efforts to understand how this hormone impacts growth and other physiological tasks over the course of ontogeny. Here, we combined mutations within the 13-member Arabidopsis JAZ gene family to investigate the effects of chronic JAZ deficiency on growth, defense, and reproductive output. A higher-order mutant (jaz decuple, jazD) defective in 10 JAZ genes (JAZ1-7, -9, -10, and -13) exhibited robust resistance to insect herbivores and fungal pathogens, which was accompanied by slow vegetative growth and poor reproductive performance. Metabolic phenotypes of jazD discerned from global transcript and protein profiling were indicative of elevated carbon partitioning to amino acid-, protein-, and endoplasmic reticulum body-based defenses controlled by the JA-Ile and ethylene branches of immunity. Resource allocation to a strong defense sink in jazD leaves was associated with increased respiration and hallmarks of carbon starvation but no overt changes in photosynthetic rate. Depletion of the remaining JAZ repressors in jazD further exaggerated growth stunting, nearly abolished seed production and, under extreme conditions, caused spreading necrotic lesions and tissue death. Our results demonstrate that JAZ proteins promote growth and reproductive success at least in part by preventing catastrophic metabolic effects of an unrestrained immune response.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas/imunologia , Aptidão Genética/imunologia , Isoleucina/análogos & derivados , Doenças das Plantas/genética , Proteínas Repressoras/genética , Animais , Arabidopsis/imunologia , Arabidopsis/microbiologia , Arabidopsis/parasitologia , Carbono/metabolismo , Resistência à Doença/genética , Fungos/crescimento & desenvolvimento , Fungos/patogenicidade , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Insetos/patogenicidade , Insetos/fisiologia , Isoleucina/metabolismo , Redes e Vias Metabólicas/genética , Redes e Vias Metabólicas/imunologia , Família Multigênica , Mutação , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Doenças das Plantas/parasitologia , Imunidade Vegetal/genética , Isoformas de Proteínas/deficiência , Isoformas de Proteínas/genética , Proteínas Repressoras/deficiência , Reprodução/genética , Reprodução/imunologia , Transdução de Sinais
14.
PLoS One ; 13(10): e0205008, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30300400

RESUMO

BACKGROUND: Pulmonary hypertension (PH) is a common complication of chronic respiratory disease. Recent studies have reported diabetes mellitus (DM) to be a poor prognostic factor in patients with chronic respiratory disease, including chronic obstructive pulmonary disease or interstitial pneumoniae. However, the association between DM and PH in chronic respiratory disease remains unclear. In this study, we aimed to investigate whether DM is a predictor of PH in patients with chronic respiratory disease. METHODS: We prospectively analyzed 386 patients in our hospital with chronic respiratory disease. An echocardiographic pressure gradient between the right atrium and the right ventricle of ≥ 40 mmHg was defined as PH. We compared the clinical characteristics and impact of DM between chronic respiratory disease patients with and those without PH. RESULTS: Of the 386 patients, 42 (10.9%) were diagnosed as having PH. The PH group had higher modified medical research council (mMRC) grade and complication rate of DM, but not hypertension and hyperlipidemia, when compared to the non-PH group. Multivariable logistic regression analysis revealed that mMRC scale (odds ratio 1.702, 95% confidence interval, 1.297 to 2.232, P < 0.001) and presence of DM (odd ratio 2.935, 95% confidence interval, 1.505 to 5.725, P = 0.002) were associated with PH in chronic respiratory disease patients. CONCLUSION: DM is potentially associated with PH and is an independent factor for prediction of PH in patients with chronic respiratory disease.


Assuntos
Complicações do Diabetes/patologia , Hipertensão Pulmonar/complicações , Transtornos Respiratórios/complicações , Idoso , Área Sob a Curva , Doença Crônica , Ecocardiografia , Feminino , Hemodinâmica , Humanos , Hipertensão Pulmonar/diagnóstico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Curva ROC , Transtornos Respiratórios/diagnóstico
15.
Plant Physiol ; 178(2): 552-564, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30126866

RESUMO

Green leaf volatiles (GLVs), including six-carbon (C6) aldehydes, alcohols, and esters, are formed when plant tissues are damaged. GLVs play roles in direct plant defense at wound sites, indirect plant defense via the attraction of herbivore predators, and plant-plant communication. GLV components provoke distinctive responses in their target recipients; therefore, the control of GLV composition is important for plants to appropriately manage stress responses. The reduction of C6-aldehydes into C6-alcohols is a key step in the control of GLV composition and also is important to avoid a toxic buildup of C6-aldehydes. However, the molecular mechanisms behind C6-aldehyde reduction remain poorly understood. In this study, we purified an Arabidopsis (Arabidopsis thaliana) NADPH-dependent cinnamaldehyde and hexenal reductase encoded by At4g37980, named here CINNAMALDEHYDE AND HEXENAL REDUCTASE (CHR). CHR T-DNA knockout mutant plants displayed a normal growth phenotype; however, we observed significant suppression of C6-alcohol production following partial mechanical wounding or herbivore infestation. Our data also showed that the parasitic wasp Cotesia vestalis was more attracted to GLVs emitted from herbivore-infested wild-type plants compared with GLVs emitted from chr plants, which corresponded with reduced C6-alcohol levels in the mutant. Moreover, chr plants were more susceptible to exogenous high-dose exposure to (Z)-3-hexenal, as indicated by their markedly lowered photosystem II activity. Our study shows that reductases play significant roles in changing GLV composition and, thus, are important in avoiding toxicity from volatile carbonyls and in the attraction of herbivore predators.


Assuntos
Oxirredutases do Álcool/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Hexobarbital/metabolismo , Oxirredutases/metabolismo , Compostos Orgânicos Voláteis/química , Oxirredutases do Álcool/genética , Álcoois/química , Álcoois/metabolismo , Aldeídos/química , Aldeídos/metabolismo , Arabidopsis/química , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Ésteres/química , Ésteres/metabolismo , Mutação , Oxirredutases/genética , Filogenia , Folhas de Planta/química , Folhas de Planta/enzimologia , Folhas de Planta/genética , Compostos Orgânicos Voláteis/metabolismo
16.
Urol Int ; 101(1): 74-79, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29909414

RESUMO

INTRODUCTION: We investigated whether the change in the neutrophil lymphocyte ratio (NLR) from the first to the last repeat prostate biopsy (ΔNLR) could be the diagnostic tool or not for prostate cancer (PCa) detection. MATERIALS AND METHODS: We retrospectively evaluated medical records of men who had undergone repeat prostate biopsy. The investigated parameters were white blood cell, neutrophil, lymphocyte counts, NLR at the last prostate biopsy, ΔNLR, prostate-specific antigen (PSA), PSA density (PSAD), and PSA velocity. Exclusion criteria were the presence of cancers other than prostate origin, medication, and diseases which induce the change of NLR. RESULTS: A total of 301 men who had undergone repeat prostate biopsy were selected for this study. After applying exclusion criteria, 223 patients were included. Of these patients, 94 were diagnosed with PCa (Group I) and 129 with no malignancy (Group II). Only a single patient had metastasis. On evaluating the area under the receiver operating characteristic curve of all study parameters, ΔNLR was the most accurate marker, followed by PSAD and then NLR measured at the last biopsy. CONCLUSIONS: ΔNLR was the most accurate marker to improve the total predictive value in repeat prostate biopsy for diagnosing PCa.


Assuntos
Carcinogênese , Linfócitos/citologia , Neutrófilos/citologia , Próstata/patologia , Neoplasias da Próstata/patologia , Idoso , Biomarcadores Tumorais/sangue , Biópsia , Progressão da Doença , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Valor Preditivo dos Testes , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Curva ROC , Análise de Regressão , Estudos Retrospectivos
17.
Plant Cell ; 30(7): 1445-1460, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29743197

RESUMO

The evolution of transcriptional regulatory mechanisms is central to how stress response and tolerance differ between species. However, it remains largely unknown how divergence in cis-regulatory sites and, subsequently, transcription factor (TF) binding specificity contribute to stress-responsive expression divergence, particularly between wild and domesticated species. By profiling wound-responsive gene transcriptomes in wild Solanum pennellii and domesticated S. lycopersicum, we found extensive wound response divergence and identified 493 S. lycopersicum and 278 S. pennellii putative cis-regulatory elements (pCREs) that were predictive of wound-responsive gene expression. Only 24-52% of these wound response pCREs (depending on wound response patterns) were consistently enriched in the putative promoter regions of wound-responsive genes across species. In addition, between these two species, their differences in pCRE site sequences were significantly and positively correlated with differences in wound-responsive gene expression. Furthermore, ∼11-39% of pCREs were specific to only one of the species and likely bound by TFs from different families. These findings indicate substantial regulatory divergence in these two plant species that diverged ∼3-7 million years ago. Our study provides insights into the mechanistic basis of how the transcriptional response to wounding is regulated and, importantly, the contribution of cis-regulatory components to variation in wound-responsive gene expression between a wild and a domesticated plant species.


Assuntos
Lycopersicon esculentum/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
Int J Cardiol ; 258: 269-274, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29428236

RESUMO

BACKGROUND: Pulmonary hypertension (PH) causes right ventricular dysfunction and central venous congestion, and may lead to congestive hepatopathy. The serum 7S domain of collagen type IV (P4NP 7S) is an established marker of liver fibrosis in chronic liver disease. We aimed to determine whether P4NP 7S is related to hemodynamic parameters, and assessed the potential values of P4NP 7S to predict mortality. METHODS: Consecutive 76 pre-capillary PH patients were divided into tertiles based on their serum P4NP 7S levels. We compared right-heart catheterization, echocardiographic findings, and mortality among the tertiles, and compared P4NP 7S with other known biomarkers of mortality. RESULTS: Cardiac index, mean pulmonary arterial pressure, pulmonary vascular resistance, and right ventricular fractional area change did not differ among the three groups. In contrast, compared to 1st and 2nd tertiles, the 3rd tertile had higher levels of right atrial pressure, right atrial area, and right ventricular area (P<0.05, respectively). In the Kaplan-Meier analysis, mortality progressively increased from the 1st to 2nd and 3rd tertiles (log-rank, P=0.002). In the Cox proportional hazard analysis, P4NP 7S was a predictor of mortality. ROC analysis demonstrated that a P4NP 7S concentration of 4.75ng/ml predicted mortality (AUC 0.85, 95% CI 0.75-0.94; P<0.001), and that the prognostic value of P4NP 7S was comparable or superior to that of other biomarkers (total bilirubin, creatinine, uric acid, C-reactive protein, B-type natriuretic peptide, and troponin I). CONCLUSIONS: Serum P4NP 7S is associated with higher central venous pressure, right-sided volume overload, and mortality in PH patients.


Assuntos
Capilares/diagnóstico por imagem , Colágeno Tipo IV/sangue , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/diagnóstico por imagem , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico por imagem , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Hipertensão Pulmonar/mortalidade , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Eur J Prev Cardiol ; 24(18): 1979-1987, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29086584

RESUMO

Aims We aimed to determine the differences of impact of cardiopulmonary exercise testing (CPX) parameters on prognosis of heart failure with reduced left ventricular ejection fraction (HFrEF), preserved ejection fraction (HFpEF) and mid-range ejection fraction (HFmrEF). Methods We compared clinical characteristics and CPX parameters among the three groups, and the value of each CPX parameter to predict adverse cardiac events (cardiac deaths and re-hospitalizations for heart failure), cardiac deaths and all-cause deaths. Results Of 1190 patients, 41.9% had HFrEF, 36.8% had HFpEF and 21.3% had HFmrEF. The patients in HFrEF group had higher rates of adverse cardiac events, cardiac death and all-cause death than those of HFpEF and HFmrEF groups. In HFrEF, the independent predictors of adverse cardiac events were peak oxygen consumption and oxygen uptake efficiency slope, predictors of cardiac death were peak oxygen consumption and oxygen uptake efficiency slope, and the predictor of all-cause death was peak oxygen consumption. In HFpEF, the predictor of adverse cardiac events was peak oxygen consumption, predictors of cardiac deaths and all-cause deaths were peak oxygen consumption and exertional oscillatory ventilation. In HFmrEF, predictors of adverse cardiac events were peak oxygen consumption and oxygen uptake efficiency slope, and the predictor of cardiac deaths and all-cause deaths was peak oxygen consumption. Conclusion Peak oxygen consumption is the strong predictor for adverse events in all groups. Oxygen uptake efficiency slope predicts adverse prognosis in HFrEF, but not in HFpEF. In contrast, exertional oscillatory ventilation is the predictor only in HFpEF. Thus, different CPX parameters may be able to differentially predict prognosis in HFrEF and HFpEF. Those for predicting prognosis in HFmrEF may be intermediate between HFrEF and HFpEF.


Assuntos
Teste de Esforço , Tolerância ao Exercício , Insuficiência Cardíaca/diagnóstico , Consumo de Oxigênio , Volume Sistólico , Função Ventricular Esquerda , Idoso , Causas de Morte , Progressão da Doença , Intervalo Livre de Doença , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo
20.
Int Heart J ; 58(5): 828-830, 2017 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-28966328

RESUMO

In heart failure patients, exhaled acetone concentration, a noninvasive biomarker, is increased according to heart failure severity. Moreover, exhaled acetone concentration is also known to be affected by diabetes mellitus. However, there have been no reports on exhaled acetone concentration in heart failure patients with diabetes mellitus. A 77-year old man was admitted to our hospital with acute decompensated heart failure and atrioventricular block. He had controlled diabetes mellitus under insulin treatment with hemoglobin A1c of 6.5%. He underwent treatment of diuretics and permanent pacemaker implantation. His condition improved and he was discharged at Day 12. Due to the heart failure improvement, his levels of exhaled acetone concentration decreased from 1.623 ppm at admission to 0.664 ppm at discharge. This is the first report to reveal a change of exhaled acetone concentration in a diabetic patient with acute decompensated heart failure.


Assuntos
Acetona/análise , Diabetes Mellitus Tipo 2/complicações , Insuficiência Cardíaca/complicações , Doença Aguda , Idoso , Biomarcadores/análise , Testes Respiratórios , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Progressão da Doença , Expiração , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/metabolismo , Humanos , Masculino
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