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1.
Plant Cell ; 36(4): 881-898, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37941457

RESUMO

Double fertilization in many flowering plants (angiosperms) often occurs during the hot summer season, but the mechanisms that enable angiosperms to adapt specifically to high temperatures are largely unknown. The actin cytoskeleton is essential for pollen germination and the polarized growth of pollen tubes, yet how this process responds to high temperatures remains unclear. Here, we reveal that the high thermal stability of 11 Arabidopsis (Arabidopsis thaliana) actin-depolymerizing factors (ADFs) is significantly different: ADFs that specifically accumulate in tip-growing cells (pollen and root hairs) exhibit high thermal stability. Through ancestral protein reconstruction, we found that subclass II ADFs (expressed specifically in pollen) have undergone a dynamic wave-like evolution of the retention, loss, and regeneration of thermostable sites. Additionally, the sites of AtADF7 with high thermal stability are conserved in ADFs specific to angiosperm pollen. Moreover, the high thermal stability of ADFs is required to regulate actin dynamics and turnover at high temperatures to promote pollen germination. Collectively, these findings suggest strategies for the adaptation of sexual reproduction to high temperature in angiosperms at the cell biology level.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Fatores de Despolimerização de Actina/metabolismo , Actinas/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Temperatura , Germinação/genética , Arabidopsis/metabolismo , Pólen/metabolismo , Tubo Polínico
2.
Small ; : e2406542, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39308242

RESUMO

P2-type Mn-based layered oxides have emerged as one of the most promising cathode materials for sodium-ion batteries owing to their advantages of facile preparation and high theoretical capacity. However, challenges such as phase transition and irreversible oxygen release during cycling often lead to rapid structural distortion and the formation of oxygen vacancies, ultimately resulting in rapid capacity decay. Herein, a covalency modulation strategy is adopted to address these challenges and successfully achieved a stable P2-type Mn-based layered oxide by introducing strong covalent Ni─O bonds. The robust Ni─O motif plays a crucial role in maintaining the rigidity of transition metal (TM) layered frameworks, which efficiently alleviates the structural distortion and degradation of the coordination environments of local TM sites, thereby achieving durable structural stiffness over extended cycles. In addition, the strong covalent Ni─O bonds can also stabilize the local oxygen environment, effectively suppressing the irreversible oxygen release. Benefiting from these advancements, the as-designed Na0.6Mg0.15Mn0.7Ni0.15O2 cathode displays a full solid-solution behavior with a low volume change of only 0.9% and an enhanced reversibility of lattice oxygen redox (OR) reaction. This investigation emphasizes the crucial role of covalency modulation in regulating OR chemistry and structural integrity to achieve high-energy-density Mn-based layered oxides.

3.
Cogn Psychol ; 153: 101683, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39217858

RESUMO

The direct-lexical-control hypothesis stipulates that some aspect of a word's processing determines the duration of the fixation on that word and/or the next. Although the direct lexical control is incorporated into most current models of eye-movement control in reading, the precise implementation varies and the assumptions of the hypothesis may not be feasible given that lexical processing must occur rapidly enough to influence fixation durations. Conclusive empirical evidence supporting this hypothesis is therefore lacking. In this article, we report the results of an eye-tracking experiment using the boundary paradigm in which native speakers of Chinese read sentences in which target words were either high- or low-frequency and preceded by a valid or invalid preview. Eye movements were co-registered with electroencephalography, allowing standard analyses of eye-movement measures, divergence point analyses of fixation-duration distributions, and fixated-related potentials on the target words. These analyses collectively provide strong behavioral and neural evidence of early lexical processing and thus strong support for the direct-lexical-control hypothesis. We discuss the implications of the findings for our understanding of how the hypothesis might be implemented, the neural systems that support skilled reading, and the nature of eye-movement control in the reading of Chinese versus alphabetic scripts.


Assuntos
Eletroencefalografia , Movimentos Oculares , Tecnologia de Rastreamento Ocular , Leitura , Humanos , Movimentos Oculares/fisiologia , Feminino , Masculino , Fixação Ocular/fisiologia , Adulto Jovem , Adulto , Idioma , Potenciais Evocados/fisiologia , China , População do Leste Asiático
4.
Nucleic Acids Res ; 50(D1): D287-D294, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34403477

RESUMO

RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation. Accurate identification of RBP binding sites in multiple cell lines and tissue types from diverse species is a fundamental endeavor towards understanding the regulatory mechanisms of RBPs under both physiological and pathological conditions. Our POSTAR annotation processes make use of publicly available large-scale CLIP-seq datasets and external functional genomic annotations to generate a comprehensive map of RBP binding sites and their association with other regulatory events as well as functional variants. Here, we present POSTAR3, an updated database with improvements in data collection, annotation infrastructure, and analysis that support the annotation of post-transcriptional regulation in multiple species including: we made a comprehensive update on the CLIP-seq and Ribo-seq datasets which cover more biological conditions, technologies, and species; we added RNA secondary structure profiling for RBP binding sites; we provided miRNA-mediated degradation events validated by degradome-seq; we included RBP binding sites at circRNA junction regions; we expanded the annotation of RBP binding sites, particularly using updated genomic variants and mutations associated with diseases. POSTAR3 is freely available at http://postar.ncrnalab.org.


Assuntos
Bases de Dados Genéticas , MicroRNAs/genética , Processamento Pós-Transcricional do RNA , RNA Circular/genética , Proteínas de Ligação a RNA/genética , Software , Animais , Arabidopsis/genética , Arabidopsis/metabolismo , Sítios de Ligação , Linhagem Celular , Conjuntos de Dados como Assunto , Humanos , Internet , MicroRNAs/classificação , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Conformação de Ácido Nucleico , RNA Circular/classificação , RNA Circular/metabolismo , Proteínas de Ligação a RNA/classificação , Proteínas de Ligação a RNA/metabolismo , Análise de Sequência de RNA
5.
J Transl Med ; 21(1): 413, 2023 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-37355631

RESUMO

In recent decades, the incidence of thyroid cancer keeps growing at a shocking rate, which has aroused increasing concerns worldwide. Autophagy is a fundamental and ubiquitous biological event conserved in mammals including humans. Basically, autophagy is a catabolic process that cellular components including small molecules and damaged organelles are degraded for recycle to meet the energy needs, especially under the extreme conditions. The dysregulated autophagy has indicated to be involved in thyroid cancer progression. The enhancement of autophagy can lead to autophagic cell death during the degradation while the produced energies can be utilized by the rest of the cancerous tissue, thus this influence could be bidirectional, which plays either a tumor-suppressive or oncogenic role. Accordingly, autophagy can be suppressed by therapeutic agents and is thus regarded as a drug target for thyroid cancer treatments. In the present review, a brief description of autophagy and roles of autophagy in tumor context are given. We have addressed summary of the mechanisms and functions of autophagy in thyroid cancer. Some potential autophagy-targeted treatments are also summarized. The aim of the review is linking autophagy to thyroid cancer, so as to develop novel approaches to better control cancer progression.


Assuntos
Neoplasias , Neoplasias da Glândula Tireoide , Animais , Humanos , Neoplasias/patologia , Autofagia/fisiologia , Mamíferos
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(2): 128-134, 2023 Feb 15.
Artigo em Zh | MEDLINE | ID: mdl-36854687

RESUMO

OBJECTIVES: To explore a new method for electroencephalography (EEG) background analysis in neonates with hypoxic-ischemic encephalopathy (HIE) and its relationship with clinical grading and head magnetic resonance imaging (MRI) grading. METHODS: A retrospective analysis was performed for the video electroencephalography (vEEG) and amplitude-integrated electroencephalography (aEEG) monitoring data within 24 hours after birth of neonates diagnosed with HIE from January 2016 to August 2022. All items of EEG background analysis were enrolled into an assessment system and were scored according to severity to obtain the total EEG score. The correlations of total EEG score with total MRI score and total Sarnat score (TSS, used to evaluate clinical gradings) were analyzed by Spearman correlation analysis. The total EEG score was compared among the neonates with different clinical gradings and among the neonates with different head MRI gradings. The receiver operating characteristic (ROC) curve and the area under thecurve (AUC) were used to evaluate the value of total EEG score in diagnosing moderate/severe head MRI abnormalities and clinical moderate/severe HIE, which was then compared with the aEEG grading method. RESULTS: A total of 50 neonates with HIE were included. The total EEG score was positively correlated with the total head MRI score and TSS (rs=0.840 and 0.611 respectively, P<0.001). There were significant differences in the total EEG score between different clinical grading groups and different head MRI grading groups (P<0.05). The total EEG score and the aEEG grading method had an AUC of 0.936 and 0.617 respectively in judging moderate/severe head MRI abnormalities (P<0.01) and an AUC of 0.887 and 0.796 respectively in judging clinical moderate/severe HIE (P>0.05). The total EEG scores of ≤6 points, 7-13 points, and ≥14 points were defined as mild, moderate, and severe EEG abnormalities respectively, which had the best consistency with clinical grading and head MRI grading (P<0.05). CONCLUSIONS: The new EEG background scoring method can quantitatively reflect the severity of brain injury and can be used for the judgment of brain function in neonates with HIE.


Assuntos
Lesões Encefálicas , Hipóxia-Isquemia Encefálica , Recém-Nascido , Humanos , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Estudos Retrospectivos , Eletroencefalografia , Curva ROC
7.
Sensors (Basel) ; 23(1)2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36616865

RESUMO

The precise three-dimensional measurement of fuel nozzles is of great significance to assess the manufacturing accuracy and improve the spray and atomization performance. This paper proposes an improved fast shape from focus (SFF) method for three-dimensional measurement of key features of fuel nozzles. In order to ensure the measurement accuracy and efficiency of the SFF, the dispersion of the measured points from a standard flat plane was used to select the optimal combination of the focus measure operator, window size and sampling step size. In addition, an approximate method for the focus measure interval is proposed to improve the measurement efficiency, which uses the peak region of the central pixel to replace the peak region of other pixels. The results show that the proposed method decreased the average computation time of the focus measure by 79.19% for the cone section and by 38.30% for the swirl slot. Compared with a reference laser scanning microscope, the measurement error in length is within 10 µm and the error in angle is within a maximum 0.15°.

8.
Small ; 17(31): e2008177, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34185956

RESUMO

Ultrasound-targeted microbubble destruction (UTMD) mediates gene transfection with high biosafety and thus has been promising toward treatment of type 1 diabetes. However, the potential application of UTMD in type 2 diabetes (T2D) is still limited, due to the lack of systematic design and dynamic monitoring. Herein, an efficient gene delivery system is constructed by plasmid deoxyribonucleic acid (DNA) encoding glucagon-like peptide 1 (GLP-1) in ultrasound-induced microbubbles, toward treatment of T2D in macaque. The as designed UTMD afforded enhancement of cell membrane penetration and GLP-1 expression in macaque, which is characterized by ultrasound-guided biopsy to monitor the dynamic process of islet cells for 6 months. Also, improvement of pancreatic beta cell regeneration, and regulation of plasma glucose in macaque with T2D is achieved. The approach would serve as promising alternatives for the treatment of T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Técnicas de Transferência de Genes , Glucose , Humanos , Microbolhas , Regeneração , Transfecção
9.
Eur J Vasc Endovasc Surg ; 62(3): 358-366, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34266763

RESUMO

OBJECTIVE: Plaque elasticity and intraplaque neovascularisation are strongly suggestive of vulnerable plaque. This study aimed to investigate the relationship between intraplaque neovascularisation and plaque elasticity, and to compare the ultrasound findings with histopathological changes. METHODS: Patients enrolled in this study presented with symptomatic carotid stenosis (> 70%) and later underwent both pre-operative ultrasonography and endarterectomy. Contrast enhanced ultrasound (CEUS) and shear wave elastography (SWE) were used to measure the neovascularisation and elasticity of the plaque, respectively. After removal, plaques were histologically assessed to determine the microvessel density (MVD), matrix metalloproteinase (MMP)-9 expression, and type I/type III collagen ratio using immunohistochemistry staining and morphometry. A correlation analysis was used to establish the relationship among the aforementioned quantitative parameters. Inter- and intra-observer consistency evaluations were performed using the intraclass correlation coefficient and Bland-Altman plots. RESULTS: Ninety-four symptomatic patients with 98 plaques were included. The area under the curve (AUC) of the carotid plaque detected using CEUS correlated with its shear wave velocity (SWV) (r = -.714; p < .001), MVD (r = .842; p < .001), collagen type I/III ratio (r = -.833; p < .001), and MMP-9 (r = .738; p < .001). SWE was positively correlated with the type I/III collagen ratio (r = .805; p < .001). The overall interexaminer consistency of the SWE was acceptable (r = .638; p < .001). The interobserver correlation coefficient of the AUC, time to peak (TP), mean transit time (MTT), and SWV were .719, .756, .733, and .686, respectively. The intra-observer variability values of the AUC, TP, MTT, and SWV were .826, .845, .633, and .748, respectively. CONCLUSION: SWE and CEUS can comprehensively evaluate the vulnerability of the carotid plaque by assessing the elasticity of the plaque and neovascularisation within it. The negative correlation between the intraplaque neovascularisation and elasticity, further validated by histological findings, suggests that the more abundant the neovascularisation, the less elasticity.


Assuntos
Artérias Carótidas/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Técnicas de Imagem por Elasticidade , Elasticidade , Neovascularização Patológica/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Adulto , Idoso , Área Sob a Curva , Artérias Carótidas/patologia , Estenose das Carótidas/patologia , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Variações Dependentes do Observador , Placa Aterosclerótica/patologia , Medição de Risco
10.
Ecotoxicol Environ Saf ; 211: 111893, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33461016

RESUMO

In this study, electric field and ball milling were used to leach Mn2+ from low-grade pyrolusite (LGP). The effects of current density, reaction time, reaction temperature, ball-to-powder weight ratio, and ball milling time on the leaching efficiency of Mn2+ from LGP as well as the leaching mechanism were systematically studied. The results showed that the combined use of electric field and ball milling enhanced the leaching of Mn2+ from LGP. The leaching efficiency of Mn2+ reached 97.79% under the optimum conditions of LGP-to-pyrite mass ratio of 1:0.18, current density of 30 mA/cm2, LGP-to-H2SO4 mass ratio of 1:0.4, liquid-to-solid ratio of 5:1, ball-to-powder weight ratio of 1:1, ball milling time of 2 h, temperature of 80 °C, and leaching duration of 120 min. This value was 25.95% higher than that attained without ball milling and 41.45% higher than that attained when neither ball milling nor electric field was employed. Pyrite was fully oxidized to generate additional SO42- and Fe3+, and was further hydrolyzed to form jarosite (KFe3(SO4)2(OH)6) and hydronium jarosite (Fe3(SO4)2(OH)5·2H2O) via ball milling and electric field application. Moreover, the electric field changed the surface charge distribution of the mineral particles and promoted collisions between them as well as the collapse of the crystal lattice, further improving the leaching efficiency of Mn2+ from LGP. This study provided a new method for leaching Mn from LGP.


Assuntos
Manganês/química , Modelos Químicos , Compostos Férricos , Ferro , Compostos de Manganês , Óxidos , Sulfatos , Sulfetos
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(9): 909-915, 2021.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-34535205

RESUMO

OBJECTIVES: To study the correlation of electroencephalogram (EEG) background evolution with the degree of brain injury in neonates with hypoxic-ischemic encephalopathy (HIE). METHODS: A retrospective analysis was performed for 56 neonates with HIE who underwent continuous video electroencephalogram (cVEEG) and brain magnetic resonance imaging (MRI) examinations. According to clinical symptoms, they were divided into a mild group with 3 neonates, a moderate group with 36 neonates, and a severe group with 17 neonates. EEG background grading and MRI score were determined for each group to analyze the correlation of EEG background evolution with the degree of brain injury. RESULTS: Compared with the moderate group, the severe group had significantly lower gestational age and Apgar score at 5 minutes after birth, a significantly higher resuscitation score, significantly lower base excess in umbilical cord blood or blood gas within 1 hour, a significantly higher proportion of neonates on mechanical ventilation, and a significantly higher incidence rate of short-term adverse outcomes (P<0.05). For the neonates in the mild and moderate groups, MRI mainly showed no brain injury (67%, 2/3) and watershed injury (67%, 16/24) respectively, and EEG showed mild abnormality in 62% (13/21) of the neonates on the 3rd day after birth. For the neonates in the severe group, MRI mainly showed basal ganglia/thalamus + brainstem injury (24%, 4/17) and whole brain injury (71%, 12/17), and EEG showed moderate or severe abnormalities on the 3rd day after birth. EEG background grading was correlated with clinical grading, MRI score, and short-term outcome on days 1, 2, 3 and 7-14 after birth (P<0.01). The highest correlation coefficient between EEG grading and MRI score was observed on the 3rd day after birth (rs=0.751, P<0.001), and the highest correlation coefficients between EEG grading and clinical grading (rs=0.592, P=0.002) and between EEG grading and short-term outcome (rs=0.737, P<0.001) were observed 7-14 days after birth. Among the neonates with severe abnormal EEG, the neonates without brain electrical activity had the highest MRI score, followed by those with status epileptics and persistent low voltage (P<0.05). CONCLUSIONS: There is a good correlation between EEG background grading and degree of brain injury in neonates with HIE, which can help to evaluate the degree and prognosis of brain injury in the early stage.


Assuntos
Lesões Encefálicas , Hipóxia-Isquemia Encefálica , Encéfalo/diagnóstico por imagem , Eletroencefalografia , Humanos , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Imageamento por Ressonância Magnética , Estudos Retrospectivos
12.
J Formos Med Assoc ; 119(7): 1219-1229, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31744647

RESUMO

BACKGROUND/PURPOSE: Sarcopenia is prevalent in chronic hemodialysis patients. This prospective cohort study evaluated the impact of sarcopenia and its diagnostic criteria on hospitalization and mortality in 126 chronic hemodialysis patients. METHODS: Skeletal muscle mass, handgrip strength (HGS), gait speed, and blood parameters were assessed. Sarcopenia was evaluated using the criteria of the European Working Group on Sarcopenia in Older People and the Taiwanese criteria for Sarcopenia. Muscle quality was defined as HGS divided by mid-arm muscle circumference. RESULTS: Prevalences of uremic sarcopenia were 8.7% and 13.5% according to Taiwanese and European criteria, respectively. Low HGS and gait speed were much more prevalent than low muscle mass. Within 3 years, 79 (62.7%) patients were hospitalized and 26 (20.6%) died. Low HGS and slow gait speed were associated with hospitalization and mortality, while sarcopenia was associated with mortality but not with hospitalization. Notably, in our patients without sarcopenia, close associations between increased hospitalization and mortality risk with low HGS and slow gait speed remained unchanged. In Cox proportional hazard analysis, muscle quality [hazard ratio (HR) = 0.42, 95% confidence interval (CI) = 0.19-0.93, p = 0.032] and serum creatinine (HR = 0.82, 95% CI = 0.71-0.95, p = 0.009) were independently associated with composite outcome of hospitalization or death. CONCLUSION: Muscle functionality and quality can predict hospitalization and overall survival in chronic hemodialysis patients, better than muscle mass.


Assuntos
Hospitalização , Músculo Esquelético , Sarcopenia , Idoso , Idoso de 80 Anos ou mais , Força da Mão , Humanos , Estudos Longitudinais , Força Muscular , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Estudos Prospectivos , Diálise Renal , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia
13.
Hum Mol Genet ; 26(6): 1182-1192, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28158561

RESUMO

Fabry disease is caused by deficient activity of α-galactosidase A and subsequent accumulation of glycosphingolipids (mainly globotriaosylceramide, Gb3), leading to multisystem organ dysfunction. Oxidative stress and nitric oxide synthase (NOS) uncoupling are thought to contribute to Fabry cardiovascular diseases. We hypothesized that decreased tetrahydrobiopterin (BH4) plays a role in the pathogenesis of Fabry disease. We found that BH4 was decreased in the heart and kidney but not in the liver and aorta of Fabry mice. BH4 was also decreased in the plasma of female Fabry patients, which was not corrected by enzyme replacement therapy (ERT). Gb3 levels were inversely correlated with BH4 levels in animal tissues and cultured patient cells. To investigate the role of BH4 deficiency in disease phenotypes, 12-month-old Fabry mice were treated with gene transfer-mediated ERT or substrate reduction therapy (SRT) for 6 months. In the Fabry mice receiving SRT but not ERT, BH4 deficiency was restored, concomitant with ameliorated cardiac and renal hypertrophy. Additionally, glutathione levels were decreased in Fabry mouse tissues in a sex-dependent manner. Renal BH4 levels were closely correlated with glutathione levels and inversely correlated with cardiac and kidney weight. In conclusion, this study showed that BH4 deficiency occurs in Fabry disease and may contribute to the pathogenesis of the disease through oxidative stress associated with a reduced antioxidant capacity of cells and NOS uncoupling. This study also suggested dissimilar efficacy of ERT and SRT in correcting pre-existing pathologies in Fabry disease.


Assuntos
Biopterinas/análogos & derivados , Terapia de Reposição de Enzimas , Doença de Fabry/genética , alfa-Galactosidase/genética , Animais , Biopterinas/deficiência , Biopterinas/genética , Biopterinas/metabolismo , Modelos Animais de Doenças , Doença de Fabry/mortalidade , Doença de Fabry/fisiopatologia , Feminino , Glutationa/metabolismo , Glicoesfingolipídeos/metabolismo , Humanos , Rim/metabolismo , Rim/patologia , Camundongos , Miocárdio/metabolismo , Miocárdio/patologia , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Estresse Oxidativo/genética , alfa-Galactosidase/biossíntese , alfa-Galactosidase/metabolismo
14.
BMC Nephrol ; 20(1): 54, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764799

RESUMO

BACKGROUND: Sarcopenia, defined as low muscle mass and strength, is highly prevalent in patients undergoing chronic hemodialysis (HD). However, muscle function and muscle mass do not share the same clinical relevance. In fact, muscle strength was more closely associated with the risk of mortality in chronic HD patients than was muscle mass. Therefore, to identify the risk factors of muscle weakness is vital. Angiotensin II overexpression had been recognized to impair skeletal muscle strength. Accordingly, angiotensin II receptor blockers (ARBs) potentially possess a muscle protective effect. This cross-sectional study aimed to identify the factors associated with low muscle strength and to explore the relationship between ARB use and muscle strength in chronic HD patients. METHODS: A total of 120 chronic HD patients, aged 63.3 ± 13.2 years, were included in this study. Basic characteristics, handgrip strength (HGS), body composition, and nutritional status were assessed, and blood samples for biochemical tests were obtained. We divided these participants into normal- and low HGS groups according to the consensus of the European Working Group on Sarcopenia in Older People (EWGSOP). RESULTS: We observed that 78 (65.0%) patients had low HGS. In our cohort, we found that height (r = 0.653; P <  0.001), weight (r = 0.496; P <  0.001), body mass index (r = 0.215; P = 0.020), skeletal muscle index (r = 0.562; P <  0.001), albumin (r = 0.197; P = 0.032), and serum creatinine (r = 0.544; P <  0.001) were positively and age (r = - 0.506; P <  0.001), subjective global assessment (SGA) score (r = - 0.392; P <  0.001), fractional clearance index for urea (Kt/V) (r = - 0.404; P <  0.001) and urea reduction ratio (URR) (r = - 0.459; P <  0.001) were negatively correlated with HGS. According to our analysis, age (Odds ratio, OR = 1.11, 95% confidence interval, 95% CI = 1.05-1.17, P <  0.001), HD duration (OR = 1.01, 95% CI = 1.00-1.02, P = 0.010), diabetes (OR = 13.33, 95% CI = 3.45-51.53, P <  0.001), Kt/V (OR = 1.61, 95% CI = 1.06-2.46, P = 0.027), and SGA score (OR = 1.19, 95% CI = 1.03-1.38, P = 0.017) were regarded as independent predictors of low HGS. In contrast, ARB use (OR = 0.25, 95% CI = 0.07-0.93, P = 0.039) was independently associated with preserved HGS in chronic HD patients, after adjustment for multiple confounding factors. CONCLUSIONS: Our study is the first report in chronic HD patients to indicate a potentially protective effect of ARB on muscle strength. However, further longitudinal follow-up and intervention studies are needed to confirm this finding.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Força da Mão , Diálise Renal/efeitos adversos , Sarcopenia/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Composição Corporal , Estudos Transversais , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Força Muscular , Estado Nutricional , Sarcopenia/etiologia
15.
Int Heart J ; 60(5): 1154-1160, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31484855

RESUMO

In-stent neoatherosclerosis is an important problem after percutaneous coronary intervention. To explore the mechanisms and treatment of in-stent neoatherosclerosis, an animal model is needed. To avoid the disadvantages of current animal models, such as excessive use of X-rays and a high mortality rate, we attempted to develop an improved animal model. We explored a method that uses a short time interval to establish a rabbit model of in-stent neoatherosclerosis with a high survival rate and to evaluate its indicators. Sixty rabbits were divided into three equal groups: group A, the traditional method; group B, the standard intervention method; and group C, the improved method. In group C, we made two small incisions in each rabbit's neck, separated the common carotid, punctured it, and implanted a stent. The incision was then sutured. Four weeks later, we used optical coherence tomography (OCT) to scan all rabbits for neoatherosclerosis. We found no significant differences in OCT data between our new animal model and the traditional and interventional groups (P > 0.05). The technological success rate was higher in the new animal model (P < 0.001). We developed a new method to establish an animal model of neoatherosclerosis, which had similar results to the traditional and interventional methods.


Assuntos
Reestenose Coronária/diagnóstico por imagem , Estenose Coronária/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Stents/efeitos adversos , Tomografia de Coerência Óptica/métodos , Animais , Reestenose Coronária/mortalidade , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/mortalidade , Modelos Animais de Doenças , Humanos , Masculino , Neointima/diagnóstico por imagem , Neointima/patologia , Variações Dependentes do Observador , Intervenção Coronária Percutânea/métodos , Intervenção Coronária Percutânea/mortalidade , Falha de Prótese , Coelhos , Distribuição Aleatória , Fatores de Risco , Estatísticas não Paramétricas , Taxa de Sobrevida
16.
Hum Mutat ; 39(4): 550-562, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29297599

RESUMO

Rare variants are considered underlying causes of complex diseases. The complex and severe group of disorders called neural tube defects (NTDs) results from failure of the neural tube to close during early embryogenesis. Neural tube closure requires the coordination of numerous signaling pathways, including the precise regulation of retinoic acid (RA) concentration, which is controlled by enzymes involved in RA synthesis and degradation. Here, we used a case-control mutation screen study to reveal rare variants in retinoid-related genes in a Han Chinese NTD population by sequencing six genes in 355 NTD cases and 225 controls. More specific rare variants were found in exonic and upstream regions in NTD cases. The RA-responsive genes CYP26A1, CRABP1, and ALDH1A2 harbored NTD-specific rare variants in their upstream regions. Unexpectedly, the majority of missense variants in NTD cases were found in CYP26B1, which encodes a RA degradation enzyme, whereas no missense variants in this gene were found in controls. Functional analysis indicated that the CYP26B1 NTD variants were inefficient in the degradation of RA using assays of RA-induced transcription and RA-initiated neuronal differentiation. Our study supports the contribution of rare variants in RA-related genes to the etiology of human NTDs.


Assuntos
Defeitos do Tubo Neural/genética , Receptores do Ácido Retinoico/genética , Retinal Desidrogenase/genética , Ácido Retinoico 4 Hidroxilase/genética , Tretinoína/metabolismo , Família Aldeído Desidrogenase 1 , Estudos de Casos e Controles , Criança , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Desenvolvimento Embrionário , Humanos , Lactente , Recém-Nascido , Mutação
17.
Biochemistry ; 57(31): 4663-4674, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-29474059

RESUMO

Protein homeostasis, or proteostasis, is essential for cellular fitness and viability. Many environmental factors compromise proteostasis, induce global proteome stress, and cause diseases. The proteome stress sensor is a powerful tool for dissecting the mechanism of cellular stress and finding therapeutics that ameliorate these diseases. In this work, we present a multicolor HaloTag-based sensor (named AgHalo) to visualize and quantify proteome stresses in live cells. The current AgHalo sensor is equipped with three fluorogenic probes that turn on fluorescence when the sensor forms either soluble oligomers or insoluble aggregates upon exposure to stress conditions, both in vitro and in cellulo. In addition, AgHalo probes can be combined with commercially available always-fluorescent HaloTag ligands to enable two-color imaging, allowing for direct visualization of the AgHalo sensor both before and after cells are subjected to stress conditions. Finally, pulse-chase experiments can be performed to discern changes in the cellular proteome in live cells by first forming the AgHalo conjugate and then either applying or removing stress at any desired time point. In summary, the AgHalo sensor can be used to visualize and quantify proteome stress in live cells, a task that is difficult to accomplish using previous always-fluorescent methods. This sensor should be suited to evaluating cellular proteostasis under various exogenous stresses, including chemical toxins, drugs, and environmental factors.


Assuntos
Proteoma/análise , Técnicas Biossensoriais/métodos , Eletroforese em Gel de Poliacrilamida , Corantes Fluorescentes , Células HEK293 , Humanos , Microscopia de Fluorescência , Agregados Proteicos/fisiologia , Dobramento de Proteína , Proteostase/fisiologia , Espectrometria de Fluorescência
18.
Gene Ther ; 25(7): 497-509, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30072816

RESUMO

Here we present our progress in inducing an ectopic brown adipose tissue (BAT) phenotype in skeletal muscle (SKM) as a potential gene therapy for obesity and its comorbidities. We used ultrasound-targeted microbubble destruction (UTMD), a novel targeted, non-viral approach to gene therapy, to deliver genes in the BAT differentiation pathway into rodent SKM to engineer a thermogenic BAT phenotype with ectopic mUCP-1 overexpression. In parallel, we performed a second protocol using wild-type Ucp-1-null knockout mice to test whether the effects of the gene therapy are UCP-1 dependent. Our main findings were a robust cellular presence of mUCP-1 immunostaining (IHC), significantly higher expression levels of mUCP-1 measured by qRT-PCR, and highest temperature elevation measured by infrared thermography in the treated thigh, achieved in rats after delivering the UTMD-PRDM16/PGC-1a/BMP7/hyPB gene cocktail. Interestingly, the weight loss obtained in the treated rats with the triple gene delivery, never recovered the levels observed in the controls in spite of food intake recovery. Our results establish the feasibility of minimally invasive UTMD gene-based therapy administration in SKM, to induce overexpression of ectopic mUCP-1 after delivery of the thermogenic BAT gene program, and describe systemic effects of this intervention on food intake, weight loss, and thermogenesis.


Assuntos
Tecido Adiposo Marrom/metabolismo , Terapia Genética , Obesidade/terapia , Proteína Desacopladora 1/genética , Tecido Adiposo Marrom/transplante , Animais , Ingestão de Alimentos/genética , Regulação da Expressão Gênica , Camundongos , Camundongos Knockout , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Ratos , Termogênese/genética , Proteína Desacopladora 1/administração & dosagem
19.
J Inherit Metab Dis ; 41(2): 231-238, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29110178

RESUMO

Fabry disease is a glycosphingolipidosis caused by deficient activity of α-galactosidase A; it is one of a few diseases that are associated with priapism, an abnormal prolonged erection of the penis. The goal of this study was to investigate the pathogenesis of Fabry disease-associated priapism in a mouse model of the disease. We found that Fabry mice develop late-onset priapism. Neuronal nitric oxide synthase (nNOS), which was predominantly present as the 120-kDa N-terminus-truncated form, was significantly upregulated in the penis of 18-month-old Fabry mice compared to wild type controls (~fivefold). Endothelial NOS (eNOS) was also upregulated (~twofold). NO level in penile tissues of Fabry mice was significantly higher than wild type controls at 18 months. Gene transfer-mediated enzyme replacement therapy reversed abnormal nNOS expression in the Fabry mouse penis. The penile nNOS level was restored by antiandrogen treatment, suggesting that hyperactive androgen receptor signaling in Fabry mice may contribute to nNOS upregulation. However, the phosphodiesterase-5A expression level and the adenosine content in the penis, which are known to play roles in the development of priapism in other etiologies, were unchanged in Fabry mice. In conclusion, these data suggested that increased nNOS (and probably eNOS) content and the consequential elevated NO production and high arterial blood flow in the penis may be the underlying mechanism of priapism in Fabry mice. Furthermore, in combination with previous findings, this study suggested that regulation of NOS expression is susceptible to α-galactosidase A deficiency, and this may represent a general pathogenic mechanism of Fabry vasculopathy.


Assuntos
Doença de Fabry/complicações , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Ereção Peniana , Pênis/enzimologia , Priapismo/etiologia , Animais , Modelos Animais de Doenças , Terapia de Reposição de Enzimas/métodos , Doença de Fabry/enzimologia , Doença de Fabry/fisiopatologia , Doença de Fabry/terapia , Terapia Genética/métodos , Masculino , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Pênis/fisiopatologia , Priapismo/enzimologia , Priapismo/fisiopatologia , Priapismo/terapia , Fluxo Sanguíneo Regional , Transdução de Sinais , Regulação para Cima , alfa-Galactosidase/biossíntese , alfa-Galactosidase/genética
20.
J Cardiovasc Pharmacol ; 72(4): 167-175, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29979351

RESUMO

During the pathogenesis of early atherosclerosis, lipid-loaded macrophages are involved in plaque development and progression. As a novel adipokine, C1q/tumor necrosis factor-related protein-9 (CTRP9) has beneficial effects in cardiovascular disease. However, previous reports have not studied whether the formation of macrophage foam cell induced by oxidized low-density lipoprotein (ox-LDL) is affected by CTRP9. According to our study, in ox-LDL-induced THP-1 macrophages, CTRP9 could reduce the quantity of lipid droplets, lower the level of cholesteryl ester (CE), promote cholesterol efflux, as well as increase the expression level of the cholesterol transport receptors ATP-binding membrane cassette transporter A1 (ABCA1) and G1 (ABCG1). In addition, the protein of LC3 II is elevated and that of p62 is decreased in CTRP9-treated foam cells by enhancing autophagy. However, using 3-methyladenine (3-MA) abolished the role of CTRP9 by inhibiting autophagy. Mechanistically, the autophagy-promoting effects of CTRP9 on foam cells was reversed by an AMPK inhibitor, Compound C, which inhibited the signaling pathway of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR). These results show that CTRP9 protects against atherosclerosis by promoting cholesterol efflux to reduce the formation of foam cell in virtue of inducing autophagy in an AMPK/mTOR signaling pathway-dependent manner.


Assuntos
Adiponectina/farmacologia , Autofagia/efeitos dos fármacos , Colesterol/metabolismo , Glicoproteínas/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Ésteres do Colesterol/metabolismo , Células Espumosas/metabolismo , Células Espumosas/patologia , Humanos , Gotículas Lipídicas/efeitos dos fármacos , Gotículas Lipídicas/metabolismo , Lipoproteínas LDL/farmacologia , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Recombinantes/farmacologia , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células THP-1 , Serina-Treonina Quinases TOR/metabolismo , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral
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