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1.
Hortic Res ; 8(1): 211, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34593780

RESUMO

Protoplast transient expression is a powerful strategy for gene functional characterization, especially in biochemical mechanism studies. We herein developed a highly efficient transient expression system for apple protoplasts. The abilities of the Arabidopsis thaliana and Malus domestica ubiquitin-10 (AtUBQ10 and MdUBQ10) promoters to drive the expression of multiple genes were compared with that of the CaMV 35S promoter, and the results revealed that the AtUBQ10 and MdUBQ10 promoters were more efficient in apple protoplasts. With this system, we demonstrated that active AtMKK7ac could activate MAPK6/3/4 signaling cascades, which further regulated MdWRKY33 phosphorylation and stability in apple. Furthermore, the ligand-induced interaction between the immune receptor AtFLS2 and the coreceptor AtBAK1 was reconstituted in apple protoplasts. We also found that the stability of the bacterial effector AvrRpt2 was regulated by feedback involving auxin and the immune regulator RIN4. The system established herein will serve as a useful tool for the molecular and biochemical analyses of apple genes.

2.
Front Endocrinol (Lausanne) ; 12: 711540, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603201

RESUMO

Objective: The aim of the study was to investigate the association between the visit-to-visit variability (VVV) of fasting plasma glucose (FPG) and arterial stiffness in Chinese adults. Methods: We performed a cohort study involving 2002 Chinese adults with no history of myocardial infarction or stroke. All the participants attended three visits (the baseline visit in 2008, the 2nd visit in 2009 and the 3rd visit in 2013). We used four measures to define the VVV of FPG across the three visits: the standard deviation (SD), the coefficient of variation (CV), the average successive variability (ASV) and the variability independent of the mean (VIM). We used brachial-ankle pulse wave velocity (ba-PWV) to measure arterial stiffness at the 2nd and the 3rd visits. Results: Compared with the lowest tertile of all the four measurements of VVV of FPG, significantly increased levels of ba-PWV change, ratio of ba-PWV change and the occurrence of the elevated ba-PWV were found in the highest tertile. The odds ratio (OR) and 95% confidence interval (CI) comparing participants in the highest tertile vs. the lowest tertile of FPG-SD was 1.37 (1.01-1.86) for risks of having elevated ba-PWV, even after adjustment for covariates including the mean FPG. Similar results were found for FPG-CV and FPG-VIM. Conclusion: Greater long-term variability of FPG was associated with an increased risk of arterial stiffness, suggesting that the VVV of FPG could be used for an early detection of subclinical atherosclerosis.

3.
J Diabetes ; 13(12): 987-997, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34259386

RESUMO

BACKGROUND: Type 2 diabetes is increasingly diagnosed at a younger age worldwide and in China. Limited data are available regarding the association between age at diabetes diagnosis and risks of albuminuria. This study sought to examine the independent effect of age at diagnosis of type 2 diabetes on the risk of albuminuria. METHODS: We used data from a nationwide multicenter study with 207 961 participants in mainland China. Age, sex, and study site were matched for 31 366 screen-detected type 2 diabetes cases and 31 366 normal controls. Age, sex, study site, and diabetes duration were matched for 7490 self-reported type 2 diabetes cases and 7490 normal controls. Risks of having albuminuria in matched type 2 diabetes vs controls were examined using multivariable logistic regression analysis in strata of age at diabetes diagnosis. RESULTS: Although the absolute rate of albuminuria is higher in older adults, the odds ratio of albuminuria in type 2 diabetes vs matched controls decreased with increasing age at diagnosis. For participants with diabetes diagnosed at an age of <50, 50 to 59, 60 to 69, or ≥70 years, the multivariable adjusted risk of albuminuria increased by 81%, 60%, 45%, and 33% for screen-detected diabetes, and 135%, 121%, 90%, and 58% for self-reported diabetes compared with their normal controls, respectively. CONCLUSIONS: A younger age at diagnosis of type 2 diabetes is associated with a more significantly elevated risk of albuminuria than an older age at diagnosis in Chinese adults.

4.
Aging (Albany NY) ; 13(7): 10075-10086, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33818417

RESUMO

OBJECTIVE: To examine the association between stage 1 hypertension defined by the 2017 American College of Cardiology and American Heart Association (ACC/AHA) guideline and risk of developing arterial stiffness. METHODS: During 2010-2015, 4595 adults aged ≥40 years without cardiovascular disease were followed up for a median of 4.3 years. BP levels at baseline were categorized into normal, elevated, stage 1 hypertension, and stage 2 hypertension. The development of arterial stiffness was defined as a normal brachial-ankle pulse wave velocity (ba-PWV) at baseline and an increased ba-PWV at follow-up. RESULTS: Compared with participants with normal BP, participants with stage 1 hypertension had a 1.48-fold increased risk of developing arterial stiffness [odds ratio (OR) =2.48; 95% confidence interval (CI) =1.59-3.85] after adjustment for cardiovascular risk factors. The association was more evident in adults aged 40-59 years (OR =4.08; 95% CI =2.06-8.08) than that in those aged ≥60 years (OR =1.47; 95% CI =0.81-2.67). A systolic BP 130~139 mmHg was significantly associated with arterial stiffness independent of diastolic BP (OR =2.90; 95% CI =1.86-4.52). Stage 1 hypertension either at baseline or at follow-up was associated with increased risks compared with normal BP at both baseline and follow-up. CONCLUSIONS: The 2017 ACC/AHA stage 1 hypertension was significantly associated with higher risks of arterial stiffness.


Assuntos
Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Rigidez Vascular/fisiologia , Adulto , Idoso , American Heart Association , Índice Tornozelo-Braço , Índice de Massa Corporal , Colesterol/sangue , Feminino , Humanos , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Estados Unidos
5.
Materials (Basel) ; 14(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33804262

RESUMO

The microstructure, precipitates, and austenite grain in high-strength low-alloy steel were characterized by optical microscope, transmission electron microscope, and laser scanning confocal microscopy to investigate the effect of Mo on the toughness of steel. The microstructure was refined and the toughness was enhanced after the addition of 0.07% Mo in steel. The addition of Mo can suppress the Widmanstätten ferrite (WF) formation and promote the transformation of acicular ferrite (AF), leading to the fine transformed products in the heat-affected zone (HAZ). The chemical composition of precipitates changed from Nb(C, N) to (Nb, Mo)(C, N) because of the addition of Mo. The calculated lattice misfit between Nb(C, N) and ferrite was approximately 11.39%, while it was reduced to 5.40% for (Nb, Mo)(C, N), which significantly affected the size and number density of precipitates. A detailed analysis of the precipitates focusing on the chemical composition, size, and number density has been undertaken to understand the contribution of Mo on the improvement of steel toughness.

6.
Metabolism ; 120: 154779, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33895182

RESUMO

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed and diagnosed based on modified criteria. However, evidence for the risks of developing subclinical atherosclerosis with MAFLD transitions according to its new definition has never been reported. METHODS: Using data from a community-based cohort, 6232 participants aged 40 years or older were included and were followed up for a median of 4.3 years during 2010-2015. Participants were categorized into four groups (stable non-MAFLD, MAFLD regressed to non-MAFLD, non-MAFLD progressed to MAFLD, and stable MAFLD). Subclinical atherosclerosis was defined as elevated carotid intima-media thickness (CIMT), elevated brachial-ankle pulse wave velocity (ba-PWV), or microalbuminuria. RESULTS: Compared with the stable non-MAFLD category, participants who progressed to MAFLD at follow-up visit had a 1.356-fold increased risk of developing elevated CIMT [odds ratio (OR) = 1.356; 95% confidence interval (CI) = 1.134-1.620], and a 1.458-fold increased risk of incident microalbuminuria (OR = 1.458; 95% CI = 1.034-2.056) after adjustment for confounders, respectively. In addition, participants with stable MAFLD showed 17.6%, 32.4%, and 35.4% increased risks of developing elevated CIMT, elevated ba-PWV and microalbuminuria, respectively. Compared with the stable MAFLD category, participants with MAFLD and low probability of fibrosis at baseline who regressed to non-MAFLD at follow-up visit had a 29.4% decreased risk of developing elevated CIMT (OR = 0.706; 95% CI = 0.507-0.984), a 43.1% decreased risk of developing elevated ba-PWV (OR = 0.569; 95% CI = 0.340-0.950), but was not significantly associated with incident microalbuminuria (OR = 0.709; 95% CI = 0.386-1.301). The decreased risks attributed to MAFLD regression were more evident in participants without diabetes or dyslipidemia, as well as in those with 0-1 metabolic risk abnormalities, respectively. CONCLUSIONS: MAFLD was significantly associated with higher risks of developing subclinical atherosclerosis. Moreover, the regression of MAFLD might modify the risks of developing subclinical atherosclerosis, especially among those with low probability of fibrosis or less metabolic risk abnormalities. Since 40% of baseline participants with missing data on MAFLD measurement at follow-up were excluded, the conclusions should be speculated with caution.


Assuntos
Aterosclerose/etiologia , Doenças Metabólicas/patologia , Hepatopatia Gordurosa não Alcoólica/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice Tornozelo-Braço , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Aterosclerose/patologia , Espessura Intima-Media Carotídea , China/epidemiologia , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Doenças Metabólicas/complicações , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/epidemiologia , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Remissão Espontânea , Fatores de Risco
7.
BMJ Open ; 11(3): e040890, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658258

RESUMO

OBJECTIVE: We aimed to examine the associations of urinary albumin-to-creatinine ratio (ACR) levels with risks of subclinical atherosclerosis, cardiovascular events and all-cause deaths. METHODS: Data from a large population-based cohort were used, which included 9580 participants aged ≥40 years free from cardiovascular diseases. Carotid intima-media thickness, brachial-ankle pulse wave velocity and ankle-brachial index were measured at baseline to assess subclinical atherosclerosis. After a median of 4.53 years' follow-up, 486 cardiovascular events and 230 all-cause deaths were recorded. RESULTS: The urinary ACR levels were categorised into three groups. Compared with the normal group (0≤ACR <7.82 mg/g), people with low-grade albuminuria (7.82≤ACR <30 mg/g) and albuminuria (ACR ≥30 mg/g) had higher levels of subclinical atherosclerosis. In prospective analysis, people with low-grade albuminuria was not significantly associated with cardiovascular events (HR=1.18; 95% CI 0.95 to 1.46], whereas people with albuminuria had a 50% higher risk of cardiovascular events (HR=1.50; 95% CI 1.11 to 2.03). People with low-grade albuminuria and albuminuria had 43% (HR=1.43; 95% CI 1.05 to 1.93) and 87% (HR=1.87; 95% CI 1.24 to 2.81) higher risks of all-cause deaths during follow-up, respectively. In stratified analysis, the association of higher ACR with risks of cardiovascular events and all-cause deaths was stronger among individuals with concomitant subclinical atherosclerosis, the presence of diabetes and more cardiovascular risk factors, respectively. CONCLUSIONS: ACR levels were positively associated with subclinical atherosclerosis and predicted the risks of cardiovascular events and all-cause deaths. Evaluation of ACR levels should be integrated into risk stratification and prevention of cardiovascular events and all-cause deaths, especially among those with pre-existing subclinical atherosclerosis and cardiometabolic abnormalities.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Adulto , Albuminas , Albuminúria , Índice Tornozelo-Braço , Espessura Intima-Media Carotídea , Creatinina , Humanos , Estudos Prospectivos , Análise de Onda de Pulso , Fatores de Risco
8.
Nanotechnology ; 32(8): 085502, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33202394

RESUMO

The immunochromatographic strip test (ICST) is a powerful on-site detection technology due to its unique advantages of simplicity, rapidity, and readability by the naked eye. Here we illustrate the potential of α-Fe2O3 polyhedrons as a novel visual label, which exhibit advantages of high stability and economy, for the detection of Listeria monocytogenes (L. monocytogenes) as a model foodborne pathogen. A low-cost and simple one-step solvothermal approach was developed for the synthesis of α-Fe2O3 polyhedrons; the average diameter of the α-Fe2O3 polyhedrons is about 200 nm. The crystal structure and morphology of α-Fe2O3 polyhedrons were characterized by x-ray diffraction and transmission electron microscope. α-Fe2O3 polyhedrons were immunized with anti-L. monocytogenes antibody to prepare an antibody-colloidal α-Fe2O3 polyhedron ICST. Visual detection can be obtained directly by the naked eye within 10 min. The detection limit of L. monocytogenes by α-Fe2O3 polyhedron ICST assay was 3.8 × 106 and 5.6 × 106 CFU/ml of pure culture and artificially spiked orange juice drink sample, respectively. Results indicated that the antibody-colloidal α-Fe2O3 polyhedron ICST is a rapid, simple, and low-cost assay. This approach showed great potential in the application of foodborne pathogen detection concerning food safety.


Assuntos
Compostos Férricos/química , Microbiologia de Alimentos/métodos , Listeria monocytogenes/isolamento & purificação , Anticorpos Antibacterianos/química , Anticorpos Imobilizados/química , Coloides , Compostos Férricos/síntese química , Imunoensaio , Limite de Detecção , Listeria monocytogenes/imunologia , Nanoestruturas/química , Fitas Reagentes/química
10.
J Diabetes ; 12(11): 781-790, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32472582

RESUMO

Hypertension is the leading global risk factor for cardiovascular disease and premature death. Recommendations from current guidelines of blood pressure (BP) management differ in many ways; therefore, we did an overview and comparative analysis of major clinical guidelines of BP management in people with and without diabetes, including the definition and classification of hypertension, initiation of antihypertensive drug therapy, BP control targets, and antihypertensive treatment strategies. BP management in patients with diabetes was discussed in great detail using both hypertension and diabetes guidelines. We conclude that high-level evidence from high-quality clinical studies is urgently needed to settle uncertainties on BP management recommendations.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipertensão/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Guias de Prática Clínica como Assunto , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial/métodos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Fatores de Risco
11.
J Ethnopharmacol ; 260: 112962, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32422357

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Grifola frondosa (GF), a high value medicinal mushroom, is popularly consumed as traditional medicines and health foods in China and Japan. It is a herbal medicine traditionally used for treating inflammation, cancer and diabetes. AIM OF THE STUDY: This study aimed to examine the anti-diabetic effects of a GF bioactive compound ergosterol peroxide (EPO), and its mechanism(s) of action in palmitate (PA)-induced C2C12 cells. MATERIALS AND METHODS: EPO was isolated and purified from GF fruiting bodies, and used to test for anti-diabetic activity in PA-induced murine C2C12 skeletal muscle cells through measuring glucose uptake, intracellular ROS production, and expressions of MAPKs, IRS-1, PI3K, Akt and GLUT-4 proteins. RESULTS: EPO significantly up-regulated glucose absorption and increased cell growth. At 5 µM, EPO significantly enhanced glucose uptake and decreased ROS formation, as well as up-regulated the expression of IRS-1, p-IRS-1, PI3K, Akt, p-Akt, and GLUT-4 proteins in PA-induced cells, while their p-JNK and p-p38 expression were down-regulated. GLUT-4 siRNA treatment effectively down-regulated the EPO-induced absorption of glucose and inhibited the expression of GLUT-4. CONCLUSION: These results suggest that the anti-diabetic effect of GF was from its bioactive compound EPO through the inhibition of ROS production, up-regulation of glucose absorption, and modulation of PI3K/Akt, MAPKs and GLUT-4 signaling transduction pathways.


Assuntos
Ergosterol/análogos & derivados , Glucose/metabolismo , Grifola , Hipoglicemiantes/farmacologia , Músculo Esquelético/efeitos dos fármacos , Palmitatos/farmacologia , Animais , Linhagem Celular , Ergosterol/isolamento & purificação , Ergosterol/farmacologia , Carpóforos , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Grifola/química , Hipoglicemiantes/isolamento & purificação , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Músculo Esquelético/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
12.
Hortic Res ; 6: 40, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30854214

RESUMO

Anthocyanins are biosynthesized on the cytosolic surface of the endoplasmic reticulum and then transported into the vacuole for storage. Glutathione S-transferases (GSTs) are considered to be responsible for the transport of anthocyanins into the vacuole. However, the regulatory mechanisms of GSTs in plants are still unclear. Here, we performed a genome-wide analysis and identified 69 GST genes in apple. The expression of MdGSTF6 was positively correlated with the anthocyanin content (r = 0.949) during 'Yanfu 8' fruit development. The overexpression of MdGSTF6 in the Arabidopsis thaliana tt19 mutant resulted in seedlings of 35S::MdGSTF6-GFP/tt19 that could accumulate anthocyanin and rescue its phenotype, suggesting that MdGSTF6 was an anthocyanin transporter. The silencing of MdGSTF6 affected anthocyanin accumulation in apple fruit. Moreover, the knockdown of MdGSTF6 by RNA interference in cultured 'Gala' seedlings inhibited anthocyanin accumulation. The interaction experiments showed that MdMYB1 could bind directly to the MdGSTF6 promoter to transcriptionally activate its expression. Collectively, our results demonstrate that MdGSTF6 encodes an important GST transporter of anthocyanins in apple fruit and provide evidence for the associated regulatory mechanisms. Therefore, MdMYB1 can not only regulate anthocyanin synthesis, but also control the transport of anthocyanin in apples. This information may be useful for further clarifying the regulation of anthocyanin transport in apple.

13.
Autophagy ; 15(8): 1419-1437, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30870073

RESUMO

N6-methyladenosine (m6A) mRNA modifications play critical roles in various biological processes. However, no study addresses the role of m6A in macroautophagy/autophagy. Here, we show that m6A modifications are increased in H/R-treated cardiomyocytes and ischemia/reperfusion (I/R)-treated mice heart. We found that METTL3 (methyltransferase like 3) is the primary factor involved in aberrant m6A modification. Silencing METTL3 enhances autophagic flux and inhibits apoptosis in H/R-treated cardiomyocytes. However, overexpression of METTL3 or inhibition of the RNA demethylase ALKBH5 has an opposite effect, suggesting that METTL3 is a negative regulator of autophagy. Mechanistically, METTL3 methylates TFEB, a master regulator of lysosomal biogenesis and autophagy genes, at two m6A residues in the 3'-UTR, which promotes the association of the RNA-binding protein HNRNPD with TFEB pre-mRNA and subsequently decreases the expression levels of TFEB. Further experiments show that autophagic flux enhanced by METTL3 deficiency is TFEB dependent. In turn, TFEB regulates the expression levels of METTL3 and ALKBH5 in opposite directions: it induces ALKBH5 and inhibits METTL3. TFEB binds to the ALKBH5 promoter and activates its transcription. In contrast, inhibition of METTL3 by TFEB does not involve transcriptional repression but rather downregulation of mRNA stability, thereby establishing a negative feedback loop. Together, our work uncovers a critical link between METTL3-ALKBH5 and autophagy, providing insight into the functional importance of the reversible mRNA m6A methylation and its modulators in ischemic heart disease. Abbreviations: ACTB, actin beta; ALKBH5, alkB homolog 5, RNA demethylase; ANXA5, annexin A5; ATG, autophagy-related; BafA, bafilomycin A1; CASP3, caspase 3; ELAVL1, ELAV like RNA binding protein 1; FTO, FTO, alpha-ketoglutarate dependent dioxygenase; GFP, green fluorescent protein; GST, glutathione S-transferase; HNRNPD, heterogeneous nuclear ribonucleoprotein D; H/R, hypoxia/reoxygenation; I/R, ischemia/reperfusion; LAD, left anterior descending; m6A, N6-methyladenosine; MEFs, mouse embryo fibroblasts; Mer, mutated estrogen receptor domains; METTL3, methyltransferase like 3; METTL14, methyltransferase like 14; mRFP, monomeric red fluorescent protein; MTORC1, mechanistic target of rapamycin kinase complex 1; NMVCs, neonatal mouse ventricular cardiomyocytes; PCNA, proliferating cell nuclear antigen; PE, phosphatidylethanolamine; PI, propidium iodide; PTMs, post-translational modifications; PVDF, polyvinylidenedifluoride; RIP, RNA-immunoprecipitation; siRNA, small interfering RNA; SQSTM1, sequestosome 1; TFEB, transcription factor EB; TUBA: tublin alpha; WTAP, WT1 associated protein; YTHDF, YTH N6-methyladenosine RNA binding protein.


Assuntos
Adenosina/análogos & derivados , Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Metiltransferases/metabolismo , Miócitos Cardíacos/metabolismo , Oxigênio/farmacologia , Adenosina/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Sequência de Bases , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Hipóxia Celular/efeitos dos fármacos , Células HEK293 , Ribonucleoproteínas Nucleares Heterogêneas Grupo D/metabolismo , Humanos , Metilação , Camundongos , Miócitos Cardíacos/efeitos dos fármacos , Regiões Promotoras Genéticas/genética , Precursores de RNA/metabolismo , Estabilidade de RNA/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ativação Transcricional/genética , Regulação para Cima/efeitos dos fármacos
14.
Plant Physiol ; 180(1): 543-558, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30782965

RESUMO

Plants have evolved many receptor-like kinases (RLKs) to sense extrinsic and intrinsic cues. The signaling pathways mediated by multiple Leucine-rich repeat (LRR) RLK (LRR-RLK) receptors require ligand-induced receptor-coreceptor heterodimerization and transphosphorylation with BRI1-ASSOCIATED RECEPTOR KINASE1 (BAK1)/SOMATIC EMBRYOGENESIS RECEPTOR KINASES family LRR-RLKs. Here we reveal an additional layer of regulation of BAK1 via a Ca2+-dependent proteolytic cleavage process that is conserved in Arabidopsis (Arabidopsis thaliana), Nicotiana benthamiana, and Saccharomyces cerevisiae The proteolytic cleavage of BAK1 is intrinsically regulated in response to developmental cues and immune stimulation. The surface-exposed Asp (D287) residue of BAK1 is critical for its proteolytic cleavage and plays an essential role in BAK1-regulated plant immunity, growth hormone brassinosteroid-mediated responses, and cell death containment. BAK1D287A mutation impairs BAK1 phosphorylation on its substrate BOTRYTIS-INDUCED KINASE1 (BIK1), and its plasma membrane localization. Intriguingly, it aggravates BAK1 overexpression-triggered cell death independent of BIK1, suggesting that maintaining homeostasis of BAK1 through a proteolytic process is crucial to control plant growth and immunity. Our data reveal that in addition to layered transphosphorylation in the receptor complexes, the proteolytic cleavage is an important regulatory process for the proper functions of the shared coreceptor BAK1 in diverse cellular signaling pathways.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Arabidopsis/citologia , Arabidopsis/efeitos dos fármacos , Proteínas de Arabidopsis/genética , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Morte Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Ácido Edético/farmacologia , Padrões Moleculares Associados a Patógenos/imunologia , Células Vegetais , Imunidade Vegetal , Plantas Geneticamente Modificadas , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteólise , Pseudomonas syringae/fisiologia , Tabaco/metabolismo
15.
J Food Drug Anal ; 27(1): 240-248, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30648577

RESUMO

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia that can lead to long-term complications including heart diseases, stroke, retinopathy, and renal failure. Treatment strategies include stimulating glucose uptake and controlling blood glucose level. Bofutsushosan (BOF) and Daisaikoto (DAI) are two herb-based kampo medicines that have been demonstrated to improve metabolism-associated disorders including obesity, hyperlipidemia, and nonalcoholic fatty liver. Given their bioactivities against metabolic syndromes, we explored in this study the effect of BOF and DAI extracts on glucose absorption and used them as source to identify phytochemical stimulator of glucose absorption. Glucose uptake and mechanistic studies were evaluated in differentiated C2C12 skeletal muscle cells, and HPLC analysis was used to determine the molecular bioactive constituents. Our results indicated that the ethanolic extracts of BOF and DAI (BOFEE and DAIEE, respectively) enhanced the glucose uptake ratio in the differentiated C2C12 cells, and further analysis identified the flavone baicalin as a major constituent capable of efficiently stimulating glucose absorption. Mechanistic studies revealed that the effect from baicalin involved the activation of IRS-1 and GLUT-4, and implicated the AMPK, PI3K/Akt, and MAPK/ERK signaling cascades. Due to its potency, we suggest that baicalin merit further evaluation as a potential candidate anti-hyperglycemic agent for the treatment and management of T2DM.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Glucose/metabolismo , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Animais , Linhagem Celular , Medicamentos de Ervas Chinesas/química , Flavonoides/análise , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Hipoglicemiantes/química , Camundongos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Nutr Neurosci ; 22(12): 840-849, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29595091

RESUMO

Objectives: This study evaluated the bioactive composition of tempeh products and examined the effects of tempeh on BV-2 microglial cell cytotoxicity, neurotrophic effects, and expression of inflammatory genes.Methods: Tempeh products included soybean fermented by Rhizopus, soybean fermented through cocultivation with Rhizopus and Lactobacillus, and red bean fermented through cocultivation with Rhizopus and Lactobacillus (RT-C). We analyzed the bioactive contents of tempeh extracts and evaluated the effects of tempeh water extract on lipopolysaccharide (LPS)-treated BV-2 cells.Results: The results showed that RT-C water extract had the highest concentrations of γ-aminobutyric acid (GABA) and anthocyanin. The tempeh water extracts, especially RT-C, reduced the formation of LPS-induced reactive oxygen species, downregulated the levels of nitric oxide synthase and phospho-cyclic-AMP response element-binding protein, and upregulated the expression of brain-derived neurotrophic factor (BDNF).Discussion: Our data demonstrate that RT-C has the highest concentrations of GABA and anthocyanin, more effectively reduces oxidative stress and inflammation, and increases the expression of BDNF in LPS-induced BV-2 cells.


Assuntos
Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Extratos Vegetais/farmacologia , Alimentos de Soja , Animais , Antocianinas/análise , Antocianinas/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Fator Neurotrófico Derivado do Encéfalo/análise , Linhagem Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/análise , Fermentação , Lactobacillus/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/análise , Extratos Vegetais/química , Rhizopus/metabolismo , Soja , Ácido gama-Aminobutírico/análise , Ácido gama-Aminobutírico/farmacologia
17.
Phys Chem Chem Phys ; 20(20): 13903-13908, 2018 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-29741176

RESUMO

Surface decoration with alkali metal adatoms has been predicted to be promising for silicene to obtain high hydrogen storage capacity. Herein, we performed a detailed study of the hydrogen storage properties of Li and Na co-decorated silicene (Li-Na-decorated silicene) based on first-principles calculations using van der Waals correction. The hydrogen adsorption behaviors, including the adsorption order, the maximum capacity, and the corresponding mechanism were analyzed in detail. Our calculations show that up to three hydrogen molecules can firmly bind to each Li atom and six for each Na atom, respectively. The hydrogen storage capacity is estimated to be as high as 6.65 wt% with a desirable average adsorption energy of 0.29 eV/H2. It is confirmed that both the charge-induced electrostatic interaction and the orbital hybridizations play a great role in hydrogen storage. Our results may enhance our fundamental understanding of the hydrogen storage mechanism, which is of great importance for the practical application of Li-Na-decorated silicene in hydrogen storage.

18.
Hortic Res ; 5: 24, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29736249

RESUMO

In plants, the vesicle fusion process plays a vital role in pathogen defence. However, the importance of the vesicle fusion process in apple ring rot has not been studied. Here, we isolated and characterised the apple syntaxin gene MdSYP121. Silencing the MdSYP121 gene in transgenic apple calli increased tolerance to Botryosphaeria dothidea infection; this increased tolerance was correlated with salicylic acid (SA) synthesis-related and signalling-related gene transcription. In contrast, overexpressing MdSYP121 in apple calli resulted in the opposite phenotypes. In addition, the results of RNA sequencing (RNA-Seq) and quantitative real-time PCR (qRT-PCR) assays suggested that MdSYP121 plays an important role in responses to oxidation-reduction reactions. Silencing MdSYP121 in apple calli enhanced the expression levels of reactive oxygen species (ROS)-related genes and the activity of ROS-related enzymes. The enhanced defence response status in MdSYP121-RNAi lines suggests that syntaxins are involved in the defence response to B. dothidea. More importantly, we showed that MdSYP121 forms a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex with MdSNAP33, and the complex may participate in regulating resistance to B. dothidea. In conclusion, by regulating the interaction of SA pathway and oxidation-reduction process, MdSYP121 can influence the pathogen infection process in apple.

19.
BMC Cardiovasc Disord ; 18(1): 32, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29433438

RESUMO

BACKGROUND: Molecular hydrogen has been shown to have antioxidant effect and have been used to prevent oxidative stress-related diseases. The goal of this study was to explore if hydrogen-rich saline (HRS) plays a cardioprotective effect on abdominal aortic constriction (AAC) induced cardiac hypertrophy in rats. 60adult Sprague-Dawley rats received surgically the AAC for 6-week. After the surgery, the rats were randomly divided into 4 groups (15 for each):1: sham-operated (sham); 2: AAC-model; 3: AAC + Low HRS (LHRS); and 4: AAC + High HRS (HHRS). The rats in sham and AAC-model groups were treated with normal saline intraperitoneally, while rats in LHRS and HHRS groups were intraperitoneally treated with 3 or 6 mL/kg HRS daily, respectively, for 6-week. RESULTS: The ratios of HW/BW and LVW/BW were shown in an order of Model > LHRS > HHRS > SHAM groups. The cardiac hypertrophy was also manifested with increased expressions of atrial natriuretic peptide (ANP), brain natriuretic peptides (BNP) and fibrosis of cardiac tissues in AAC-model group, which could likewise be restrained in LHRS and HHRS groups. Moreover, the JAK-STAT (Janus Kinase-Signal transducers and activators of transcription) signaling molecule expressions were decreased with HRS treatment. CONCLUSIONS: Our results showed a protective effect of HRS on pressure overload-induced cardiac hypertrophy in rats, which may be associated to a decreasing in JAK-STAT signaling pathway.


Assuntos
Aorta Abdominal/fisiopatologia , Aorta Abdominal/cirurgia , Pressão Arterial , Cardiomegalia/prevenção & controle , Hidratação/métodos , Hidrogênio/administração & dosagem , Janus Quinases/metabolismo , Miocárdio/enzimologia , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Cloreto de Sódio/administração & dosagem , Animais , Apoptose , Fator Natriurético Atrial/metabolismo , Cardiomegalia/enzimologia , Cardiomegalia/etiologia , Cardiomegalia/fisiopatologia , Constrição , Modelos Animais de Doenças , Fibrose , Masculino , Miocárdio/patologia , Peptídeo Natriurético Encefálico/metabolismo , Ratos Sprague-Dawley
20.
Int J Med Mushrooms ; 19(10): 915-924, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29256845

RESUMO

Xylaria nigripes, also known as Wu Ling Shen, is popular for treating insomnia and trauma in traditional Chinese medicine. This study aimed to examine the anti-inflammatory activity and bioactive constituents of cultivated X. nigripes fruiting bodies in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Results showed that among the different extracts, the hexane fraction exhibited the best protection against cell toxicity induced by 1 µg/mL LPS and the strongest inhibitory effect on nitric oxide (NO) production. This fraction led to the isolation of 2 bioactive compounds (namely, XN-CP1 and XN-CP2), which were confirmed to be ergostarien-3ß-ol and ergosterol peroxide, respectively. Although both XN-CP1 and XN-CP2 showed good inhibitory effects on NO, tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and prostaglandin E2 production in LPS-stimulated macrophages, XN-CP2 was shown to have a stronger anti-inflammatory activity; this was further supported by its strong suppressive effects on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and nuclear factor (NF)-κB activation. These results conclude that ergosterol peroxide (XN-CP2) could be the main bioactive compound contributing to the potent anti-inflammatory activity of X. nigripes, and its mechanism of action is mediated through inhibition of iNOS and COX-2 expression via the NF-κB signaling pathway.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Fatores Biológicos/isolamento & purificação , Carpóforos/química , Xylariales/química , Animais , Inibidores Enzimáticos/isolamento & purificação , Ergosterol/análogos & derivados , Ergosterol/isolamento & purificação , Macrófagos/efeitos dos fármacos , Camundongos , Células RAW 264.7
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