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1.
Drug Des Devel Ther ; 16: 1273-1287, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35517984

RESUMO

Background: Oxidative stress and inflammatory reaction play critical roles in acute myocardial infarction (AMI). Isoliquiritigenin (ISL), a flavonoid monomer extracted from licorice, has been found to have antioxidant and anti-inflammatory effects in cancer studies. Here, we tested the effect and underlying mechanisms of ISL on ischemia-induced myocardial injury in a mouse AMI model. Methods: Adult C57BL/6 mice were pre-treated by intraperitoneal injection of ISL and/or a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor ML385 for 3 days, respectively. Then, the AMI model was established by ligating the anterior descending branch of the left coronary artery. Myocardial oxidative stress status, inflammatory response, cardiac function and infarction size were assessed after 7th day of surgery. Results: Compared with sham group, the reactive oxygen species (ROS) and malondialdehyde (MDA) level in AMI group were significantly increased. However, the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) level were dramatically decreased. ISL treatment significantly reduced the myocardial infarction area, improved cardiac function, inhibited the production of ROS and MDA and reduced the consumption of SOD and GSH-Px. Interestingly, ISL could significantly increase nuclear Nrf2 and cytosolic heme oxygenase 1 (HO-1) level in the infarcted myocardium and reduce the oxidative stress after AMI. Also, ISL treatment dramatically inhibited the activation of myocardial NF-κB pathway and reduced the expression of pro-inflammatory factors in the AMI group. However, the administration of ML385 not only suppressed the Nrf2/HO-1 activation, the anti-oxidant and anti-inflammatory effects induced by ISL, but also attenuated the beneficial role of ISL on reducing infarct size and improving cardiac function in the mouse with AMI. Conclusion: The results suggested that activation of Nrf2/HO-1 pathway has an essential role in ISL-induced cardiac protection by alleviating myocardial oxidative stress and inflammation response in mice with AMI.


Assuntos
Infarto do Miocárdio , Fator 2 Relacionado a NF-E2 , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Chalconas , Modelos Animais de Doenças , Glutationa Peroxidase/metabolismo , Heme Oxigenase-1/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio , Superóxido Dismutase/metabolismo
2.
Inorg Chem ; 61(8): 3498-3507, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35175752

RESUMO

Nanoparticles exhibit unique properties due to their surface effects and small size, and their behavior at high pressures has attracted widespread attention in recent years. Herein, a series of in situ high-pressure X-ray diffraction measurements with a synchrotron radiation source and Raman scattering have been performed on HfO2 nanocrystals (NC-HfO2) with different grain sizes using a symmetric diamond anvil cell at ambient temperature. The experimental data reveal that the structural stability, phase transition behavior, and equation of state for HfO2 have an interesting size effect under high pressure. NC-HfO2 quenched to normal pressure is characterized by transmission electron microscopy to determine the changing behavior of grain size during phase transition. We found that the rotation of the nanocrystalline HfO2 grains causes a large strain, resulting in the retention of part of an orthorhombic I (OI) phase in the sample quenched to atmospheric pressure. Furthermore, the physical mechanism of the phase transition of NC-HfO2 under high pressure can be well explained by the first-principles calculations. The calculations demonstrate that NC-HfO2 has a strong surface effect, that is, the surface energy and surface stress can stabilize the structures. These studies may offer new insights into the understanding of the physical behavior of nanocrystal materials under high pressure and provide practical guidance for their realization in industrial applications.

3.
Gastrointest Endosc ; 95(1): 172-183.e2, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34224735

RESUMO

BACKGROUND AND AIMS: We previously reported a new and combined EUS-guided intervention in a patient with portal hypertension, consisting of obliteration of varices and partial splenic embolization (PSE). Performing PSE is known to diminish the increase in portal venous pressure after endoscopic intervention for varices. The aim of this study was to use multidetector CT portal venography to evaluate the anatomy of esophagogastric varices (EGV) and the impact on hemodynamics of portosystemic collaterals shortly after the concomitant procedures. METHODS: From October 2019 to December 2020, 5 patients with cirrhosis and with clinically significant portal hypertension who had variceal bleeding history and hypersplenism were treated with combined endoscopic obliteration for varices and EUS-guided PSE. Multidetector CT portal venography was applied to assess the anatomic drainage patterns of the EGV, diameters of feeders and drainage vessels, and splenic embolization rate. RESULTS: Within 5 days after concomitant endoscopic interventions, we observed decreased mean diameters of the left gastric vein, short gastric vein, and azygos vein as .3 mm, 1.0 mm, and 5.2 mm compared with 3.11 mm, 7.1 mm, and 5.4 mm before the procedures, respectively. Patients showed increased white blood cells (mean count of 2.7 × 109/L before vs 5.8 × 109/L after) and platelets (mean count of 52.8 × 109/L before vs 95.8 × 109/L after). The mean splenic embolization rate was 64.5% (range, 28.8%-84.6%). CONCLUSIONS: Our experience may illustrate an alternative technique of combining EUS-guided PSE with endoscopic therapy of varices to treat patients with portal hypertension.


Assuntos
Embolização Terapêutica , Varizes Esofágicas e Gástricas , Hiperesplenismo , Varizes , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Hemodinâmica , Humanos , Hiperesplenismo/etiologia , Hiperesplenismo/terapia
4.
Sci Total Environ ; 806(Pt 4): 150831, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34627884

RESUMO

Peatlands in northeast China are experiencing severe climate warming. Most studies on peatlands focus on the responses of CH4 dynamics to temperature. However, they rarely consider the synchronous changes in the composition of plant communities caused by the expansion of vascular plants. In this study, an experiment combined warming with the manipulation of plants to examine the concentrations of CH4 porewater and its fluxes in the mesocosm. We found that warming increased the concentration of CH4 and its fluxes relative to the control treatments, and it was strongly modulated by plant richness and functional types. The average CH4 fluxes in the warming and non-warming mesocosms varied from 72.10 to 119.44 and 97.95 to 194.43 mg m-2 h-1, respectively. Plant species richness significantly increased CH4 flux at the warming level of 3.2 °C (P < 0.01). The presence of vascular plants, such as Carex globularis and Vaccinium uliginosum, significantly increased the CH4 fluxes after warming had occurred. Our results suggest that the distinct response of CH4 to richness and species primarily stemmed from the direct or indirect effects of plant biomass and functional characteristics. Therefore, more consideration should be given to the diversity changes caused by vascular plant expansion when estimating CH4 flux in boreal peatland, especially in the context of future climate warming.


Assuntos
Metano , Plantas , Clima , Mudança Climática , Solo , Temperatura
5.
Aliment Pharmacol Ther ; 54(3): 329-338, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34157146

RESUMO

BACKGROUND: Obesity is typically associated with metabolic dysfunction, but its impact on hepatocellular carcinoma (HCC) remains unclear in patients with chronic hepatitis B (CHB). AIM: To study the effect of obesity on HCC development in patients with CHB receiving antiviral therapy. METHODS: We included patients from a Chinese multicentre, prospective, observational, treated CHB cohort in this study. General obesity was evaluated by body-mass index (BMI). Central obesity was evaluated by waist circumference, waist-to-hip ratio and waist-to-height ratio. RESULTS: A total of 5754 nucleos(t)ide analogue treated patients were enrolled in the analysis. The 5-year cumulative incidence of HCC was 2.9%. Waist-to-height ratio performed better in predicting HCC development than BMI, waist circumference or waist-to-hip ratio. Patients with central obesity (defined as waist-to-height ratio >0.5) had significantly higher 5-year incidence of HCC than those without central obesity in the overall population (3.9% vs 2.1%, hazard ratio [HR]: 2.06, P = 0.0001) and 745 propensity score matched pairs (4.7% vs 2.3%, HR: 2.04, P = 0.026), respectively. Besides cirrhosis status and aMAP HCC risk score, central obesity was also independently associated with HCC risk (HR: 1.63, P = 0.013). Waist-to-height ratio gain within 1 year was associated with a significantly higher HCC risk with an adjusted HR value of 1.88 (95% confidence interval: 1.12-3.13, P = 0.017). CONCLUSIONS: Central obesity, evaluated by the waist-to-height ratio, was associated with a twofold increase in HCC risk among CHB patients receiving antiviral treatment, highlighting the important role of abnormal metabolic function in the progression of liver disease.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Obesidade Abdominal , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Vírus da Hepatite B , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/epidemiologia , Humanos , Incidência , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/epidemiologia , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos
7.
Inorg Chem ; 60(2): 515-524, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33211969

RESUMO

Hafnium carbide (HfC) is a potential candidate of ultrahigh-temperature ceramics (UHTCs) and has attracted significantly widespread interest in recent years. Here, we have synthesized high-purity HfC samples with NaCl-type structure by using a high-pressure solid-solid reaction. The structural stability, equation of state, plastic deformation, yield strength, and bonding properties under high pressure are investigated by a series of in situ high-pressure synchrotron-radiation angle-dispersive X-ray diffraction experiments combined with first-principles calculations. The yield strength of HfC (∼18 GPa) is obtained from analyzing the plastic deformation behavior under high pressure. In addition, we have successfully prepared bulk HfC ceramics with high density using a high-pressure and high-temperature method. The synthesized sample possesses a desirable Vickers hardness of 24.2 GPa and an excellent fracture toughness of 5.0 MPa·m1/2. The present results offer insights into the achievable application of HfC ceramics under extreme conditions and provide a powerful guide for the further design and synthesis of other high-performance UHTCs.

8.
BMC Cardiovasc Disord ; 20(1): 429, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33003997

RESUMO

BACKGROUND: This study was to explore the influencing factors of atherosclerotic plaque formation and stability in patients with asymptomatic carotid atherosclerotic plaques, so as to identify the vulnerable plaques at early stage, and then find high-risk group of cardio-cerebrovascular events for early clinical intervention to reduce related mortality and disability. METHODS: A total of 302 enrolled patients with asymptomatic carotid atherosclerotic plaques were divided into 3 groups based on the results of carotid artery color Doppler ultrasound: atherosclerotic unstable plaque (UP) group, atherosclerotic stable plaque (SP) group, and control group without plaques. Serum markers were measured by ELISA. χ2 test, t test, Pearson correlation analysis, and Logistic multivariate regression analysis were used in the analysis, and P < 0.05 was considered statistically significant. RESULTS: It revealed that high MMP-9, LOX-1and YKL-40 were independent risk factors for unstable plaque formation. The area under the curve (AUC) of serum markers combined with MMP-9, LOX-1 and YKL-40 was 0.850, with sensitivity 87.67%, specificity 81.13%, and diagnostic accuracy 84.92%, which was significantly better than the individual diagnostic efficacy of other three factors. The accuracy rate of Crouse Plaque Score (CPS) in the diagnosis of vulnerable plaques was 61.90%, the 10-year ICVD diagnosis accuracy rate was 56.75%, and the diagnostic accuracy of serum markers was significantly better than CPS and 10-year ICVD. CONCLUSION: Noninvasive cervical color Doppler ultrasound combined with serum markers MMP-9, LOX-1 and YKL-40 have significant early recognition effect on asymptomatic carotid vulnerable plaque patients.


Assuntos
Doenças das Artérias Carótidas/sangue , Proteína 1 Semelhante à Quitinase-3/sangue , Ensaio de Imunoadsorção Enzimática , Metaloproteinase 9 da Matriz/sangue , Placa Aterosclerótica , Receptores Depuradores Classe E/sangue , Idoso , Doenças Assintomáticas , Biomarcadores/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Ruptura Espontânea , Ultrassonografia Doppler em Cores
9.
J Hepatol ; 73(6): 1368-1378, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32707225

RESUMO

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is the leading cause of death in patients with chronic hepatitis. In this international collaboration, we sought to develop a global universal HCC risk score to predict the HCC development for patients with chronic hepatitis. METHODS: A total of 17,374 patients, comprising 10,578 treated Asian patients with chronic hepatitis B (CHB), 2,510 treated Caucasian patients with CHB, 3,566 treated patients with hepatitis C virus (including 2,489 patients with cirrhosis achieving a sustained virological response) and 720 patients with non-viral hepatitis (NVH) from 11 international prospective observational cohorts or randomised controlled trials, were divided into a training cohort (3,688 Asian patients with CHB) and 9 validation cohorts with different aetiologies and ethnicities (n = 13,686). RESULTS: We developed an HCC risk score, called the aMAP score (ranging from 0 to 100), that involves only age, male, albumin-bilirubin and platelets. This metric performed excellently in assessing HCC risk not only in patients with hepatitis of different aetiologies, but also in those with different ethnicities (C-index: 0.82-0.87). Cut-off values of 50 and 60 were best for discriminating HCC risk. The 3- or 5-year cumulative incidences of HCC were 0-0.8%, 1.5-4.8%, and 8.1-19.9% in the low- (n = 7,413, 43.6%), medium- (n = 6,529, 38.4%), and high-risk (n = 3,044, 17.9%) groups, respectively. The cut-off value of 50 was associated with a sensitivity of 85.7-100% and a negative predictive value of 99.3-100%. The cut-off value of 60 resulted in a specificity of 56.6-95.8% and a positive predictive value of 6.6-15.7%. CONCLUSIONS: This objective, simple, reliable risk score based on 5 common parameters accurately predicted HCC development, regardless of aetiology and ethnicity, which could help to establish a risk score-guided HCC surveillance strategy worldwide. LAY SUMMARY: In this international collaboration, we developed and externally validated a simple, objective and accurate prognostic tool (called the aMAP score), that involves only age, male, albumin-bilirubin and platelets. The aMAP score (ranged from 0 to 100) satisfactorily predicted the risk of hepatocellular carcinoma (HCC) development among over 17,000 patients with viral and non-viral hepatitis from 11 global prospective studies. Our findings show that the aMAP score had excellent discrimination and calibration in assessing the 5-year HCC risk among all the cohorts irrespective of aetiology and ethnicity.


Assuntos
Carcinoma Hepatocelular , Saúde Global/estatística & dados numéricos , Hepatite Crônica , Neoplasias Hepáticas , Medição de Risco/métodos , Antivirais/uso terapêutico , Bilirrubina/análise , Plaquetas/patologia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Feminino , Hepatite Crônica/sangue , Hepatite Crônica/complicações , Hepatite Crônica/diagnóstico , Hepatite Crônica/etnologia , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Albumina Sérica/análise , /estatística & dados numéricos
10.
Phys Chem Chem Phys ; 22(9): 5018-5023, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32073074

RESUMO

As a member of the refractory metal carbide family of materials, TaC is a promising candidate for ultra-high temperature ceramics (UHTC) with desirable mechanical strength. TaC sample quality and therefore mechanical properties are strongly dependent on synthesis method, and atomistic origins of mechanical failure are difficult to assign. Here, we have successfully synthesized high quality densified TaC samples at 5.5 GPa and 1400 °C using the high pressure and high temperature (HPHT) sintering method, with Vickers hardness determined to be 20.9 GPa. First-principles calculations based on the recently developed strain-stress method show that the ideal indentation strength of TaC is about 23.3 GPa in the (11[combining macron]0)[001] direction, in excellent agreement with experimental results. The detailed indentation shear deformation analysis and structural snapshots from the calculations indicate that the slip dislocations of TaC layers are the main structural deformation mode during the Vickers indentation process, and that the strong directional Ta-C bonds are responsible for the high mechanical strength of TaC. HPHT synthesis is shown to produce TaC samples with superior strength, and together with accurate first-principles calculations offers crucial insights for rational design and synthesis of novel and advanced UHTC materials.

11.
Biochim Biophys Acta Mol Cell Res ; 1867(7): 118641, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31893523

RESUMO

Cilia are ubiquitous in mammalian cells. The formation and assembly of cilia depend on the normal functioning of the ciliary transport system. In recent years, various proteins involved in the intracellular transport of the cilium have attracted attention, as many diseases are caused by disorders in cilia formation. Intraflagellar transport 20 (IFT20) is a subunit of IFT complex B, which contains approximately 20 protein particles. Studies have shown that defects in IFT20 are associated with numerous system -related diseases, such as those of the urinary system, cardiovascular system, skeletal system, nervous system, immune system, reproductive system, and respiratory system. This review summarizes current research on IFT20.We describe studies related to the role of IFT20 in cilia formation and discuss new targets for treating diseases associated with ciliary dysplasia.


Assuntos
Transporte Biológico/genética , Proteínas de Transporte/genética , Cílios/genética , Ciliopatias/genética , Proteínas de Transporte/antagonistas & inibidores , Cílios/metabolismo , Ciliopatias/tratamento farmacológico , Ciliopatias/patologia , Humanos
12.
Inorg Chem ; 59(3): 1848-1852, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31829570

RESUMO

Among the transition metal carbides, tantalum carbide (TaC) has gained significant interest due to its attractive mechanical and electronic properties. Here, we have performed high pressure and high temperature (HPHT) measurements on the physical properties of TaC under 5.5 GPa and rhythmically increased temperatures from 1000 to 1500 °C. The microscopic deviatoric strain, Vickers hardness, fracture toughness, grain size, and microstructures are characterized by X-ray diffraction (XRD), scanning electronic microscopy (SEM), transmission electron microscopy (TEM), and microhardness tests. The results reveal that the HPHT sintering causes the densification, which increases the mechanical properties of TaC. At 5.5 GPa and 1300 °C, the Vickers hardness, fracture toughness, relative density, and Young's modulus of TaC are 21.0 GPa, 7.4 MPa m1/2, 457 GPa, and 97.7%, respectively, which are in good agreement with available experimental and theoretical values. It is found that the mechanical properties of TaC are highly impressible to the microstructures and microscopic deviatoric stress. Our cadent HPHT sintering technique will provide powerful guidance for further synthesis and design of other novel ultrahigh temperature ceramics (UHTCs).

13.
Materials (Basel) ; 12(17)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480208

RESUMO

A new mechanism of dynamic phase transformations of α2 ↔ γ in an isothermally forged γ-TiAl-based alloy that occur simultaneously during a short-term exposure at 1000 °C is identified in this study. In the heating process, γ phase significantly decreases through a phase transformation of γ → α2, while new γ lamellae are precipitated in the interior of equiaxed grains of α2 phase through a phase transformation of α2 → γ. The reasons for the presence of these two inverse phase transformations α2 ↔ γ occurring simultaneously are discussed.

14.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(1): 39-45, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30914114

RESUMO

Objective To establish and improve a primary culture method of mouse pulmonary artery smooth muscle cells (PASMCs), and explore the effects of different hypoxic conditions on the proliferation, migration, and apoptosis of PASMCs. Methods Under sterile conditions, pulmonary arteries were isolated from male mice and PASMCs were obtained using an improved method of tissue piece inoculation through digesting with trypsin. Cell morphology was observed under an inverted phase-contrast microscope, and cell growth curve was plotted by cell counting. Immunofluorescence staining of α-smooth muscle actin (α-SMA) was used to assess the cell type and purity of PASMCs. The effect of different oxygen concentrations on the proliferation of PASMCs was detected by CCK-8 assay. Under hypoxia, the migration ability of PASMCs was detected by scratch wound assay, and the expression of BAX protein was detected by Western blot analysis. Results The cells tended to be long spindle and grew in the typical "peak-valley" mode. Cells were confluent after 9 days and the growth curve presented with a sigmoidal shape. The positive expression rate of α-SMA was 96%. Compared with the normoxic group, the proliferation and migration of PASMCs significantly increased under hypoxia at all time points, and the cell proliferation and migration was the most significant under the condition of 10 mL/L oxygen content. Moreover, BAX protein level of the cells was significantly reduced under hypoxia in a time-dependent manner. Conclusion The primary PASMCs with high purity and activity can be obtained by enzyme digestion and tissue mass adherent method. PASMCs exhibit higher proliferation, increased migration, and declined apoptosis under 10 mL/L oxygen concentration.


Assuntos
Miócitos de Músculo Liso , Artéria Pulmonar , Animais , Hipóxia Celular , Proliferação de Células , Células Cultivadas , Masculino , Camundongos
15.
Reprod Fertil Dev ; 31(5): 962-971, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30811962

RESUMO

In this study we identified Elongin B, a regulatory subunit of the trimeric elongation factor Elongin ABC, which increases the overall rate of elongation by RNA polymerase II, as a major binding partner of sperm-associated antigen 16S (SPAG16S), a component of nuclear speckles. Nuclear speckles are nuclear subcompartments involved in RNA maturation. Previously, we showed that SPAG16S is essential for spermatogenesis. In the present study, a specific antibody against mouse Elongin B was generated and reacted with a protein with the predicted size of Elongin B in the testis; immunofluorescence staining revealed that the Elongin B was located in the nuclei and residual bodies. In round spermatids, Elongin B was colocalised with splicing factor SC35 (SC35), a marker of nuclear speckles. During the first wave of spermatogenesis, Elongin B transcripts were initially detected at Postnatal Day (PND) 8, and levels were greatly increased afterwards. However, Elongin B protein was only found from PND30, when germ cells progressed through spermiogenesis. Polysomal gradient analysis of Elongin B transcripts isolated from adult mouse testes revealed that most of the Elongin B mRNA was associated with translationally inactive, non-polysomal ribonucleoproteins. An RNA electrophoretic mobility shift assay demonstrated that the 3' untranslated region of the Elongin B transcript was bound by proteins present in testis but not liver extracts. These findings suggest that post-transcriptional regulation of Elongin B occurs in the testis, which is a common phenomenon during male germ cell development. As a major binding partner of SPAG16S, Elongin B may play an important role in spermatogenesis by modulating RNA maturation.


Assuntos
Elonguina/metabolismo , Espermatogênese/fisiologia , Testículo/metabolismo , Animais , Regulação da Expressão Gênica , Masculino , Camundongos , Espermatozoides/metabolismo , Transcrição Genética
16.
Int J Nanomedicine ; 14: 851-863, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30774338

RESUMO

Purpose: This study was carried out to investigate the effects of a triptolide (TP) nanosuspension and methotrexate (MTX) nanosuspension on left ventricular remodeling and cardiac function for autoimmune myocarditis (EAM) in rats. The regulating effects on inflammatory cytokines in the peripheral serum and related mechanisms are also discussed. Methods: First, TP and MTX were prepared as a nanosuspension, and the EAM model was successfully established in rats with cardiac myosin. Then, the effect of TP and MTX suspensions was tested in an EAM model. Results: Results revealed that both TP and MTX suspensions could reduce the degree of myocardial fibrosis and delay the remodeling process of the left ventricle which could further improve cardiac function. Finally, it was found that inflammatory cytokines in the peripheral serum were regulated by the nonspecific immune system and the inhibition of nuclear factor-κB signaling might have partly occurred due to this mechanism. Conclusion: In summary, this study provided a complete foundation for EAM therapy of profound clinical relevance.


Assuntos
Diterpenos/uso terapêutico , Metotrexato/uso terapêutico , Miocardite/tratamento farmacológico , Miocardite/fisiopatologia , Nanopartículas/química , Fenantrenos/uso terapêutico , Remodelação Ventricular/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Colágeno/metabolismo , Citocinas/sangue , Diterpenos/farmacologia , Compostos de Epóxi/farmacologia , Compostos de Epóxi/uso terapêutico , Testes de Função Cardíaca , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Masculino , Metotrexato/farmacologia , Miocardite/sangue , Miocardite/diagnóstico por imagem , Miocárdio/metabolismo , Miocárdio/patologia , NF-kappa B/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Tamanho da Partícula , Fenantrenos/farmacologia , Fosforilação/efeitos dos fármacos , Ratos Endogâmicos Lew , Transdução de Sinais/efeitos dos fármacos , Suspensões
17.
Medicine (Baltimore) ; 97(39): e12485, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30278536

RESUMO

In chronic heart failure (CHF), new-onset atrial fibrillation (AF) is associated with increased morbidity and mortality. We aimed to evaluate the influence of dyslipidemia on the incidence of new-onset AF in patients with CHF.In this single-center observational study, 308 patients with CHF and no history of AF were followed-up for 3 years. Of the 291 patients who attended the 1-year follow-up, 78 had developed AF (AF group; 10 deaths), while 213 had not (sinus rhythm [SR] group). Changes in lipid profile (ΔTC for total cholesterol and ΔLDLc for low-density lipoprotein cholesterol) were analyzed.The groups differed significantly regarding the decrease in lipid levels from baseline to the 1-year follow-up (AF vs SR: for ΔLDLc, 23.35 vs 7.80 mg/dL, P = .02; for ΔTC, 23.95 vs -2.76 mg/dL, P = .001). At the 3-year follow-up, new-onset AF was noted in 21 of the 188 living patients in the SR group. Cox proportional hazards analysis revealed ΔLDLc and ΔTC as independent risk factors for new-onset AF (hazard ratio, 1.018 and 1.013, respectively, per standard deviation increment), with higher incidence of new-onset AF for ΔTC > 9.65 mg/dL (P = .02) and for ΔLDLc > 9.73 mg/dL (P = .005).In CHF, pronounced decrease in LDLc and TC is associated with new-onset AF.


Assuntos
Fibrilação Atrial/complicações , Dislipidemias/complicações , Insuficiência Cardíaca/fisiopatologia , Lipídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , China/epidemiologia , LDL-Colesterol/sangue , Doença Crônica , Feminino , Seguimentos , Insuficiência Cardíaca/classificação , Insuficiência Cardíaca/complicações , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco
18.
Arterioscler Thromb Vasc Biol ; 38(6): 1309-1320, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29622561

RESUMO

OBJECTIVE: Recently, we have demonstrated that acute glucosamine-induced augmentation of protein O-linked ß-N-acetylglucosamine (O-GlcNAc) levels inhibits inflammation in isolated vascular smooth muscle cells and neointimal formation in a rat model of carotid injury by interfering with NF-κB (nuclear factor-κB) signaling. However, the specific molecular target for O-GlcNAcylation that is responsible for glucosamine-induced vascular protection remains unclear. In this study, we test the hypothesis that increased A20 (also known as TNFAIP3 [tumor necrosis factor α-induced protein 3]) O-GlcNAcylation is required for glucosamine-mediated inhibition of inflammation and vascular protection. APPROACH AND RESULTS: In cultured rat vascular smooth muscle cells, both glucosamine and the selective O-linked N-acetylglucosaminidase inhibitor thiamet G significantly increased A20 O-GlcNAcylation. Thiamet G treatment did not increase A20 protein expression but did significantly enhance binding to TAX1BP1 (Tax1-binding protein 1), a key regulatory protein for A20 activity. Adenovirus-mediated A20 overexpression further enhanced the effects of thiamet G on prevention of TNF-α (tumor necrosis factor-α)-induced IκB (inhibitor of κB) degradation, p65 phosphorylation, and increases in DNA-binding activity. A20 overexpression enhanced the inhibitory effects of thiamet G on TNF-α-induced proinflammatory cytokine expression and vascular smooth muscle cell migration and proliferation, whereas silencing endogenous A20 by transfection of specific A20 shRNA significantly attenuated these inhibitory effects. In balloon-injured rat carotid arteries, glucosamine treatment markedly inhibited neointimal formation and p65 activation compared with vehicle treatment. Adenoviral delivery of A20 shRNA to the injured arteries dramatically reduced balloon injury-induced A20 expression and inflammatory response compared with scramble shRNA and completely abolished the vascular protection of glucosamine. CONCLUSIONS: These results suggest that O-GlcNAcylation of A20 plays a key role in the negative regulation of NF-κB signaling cascades in TNF-α-treated vascular smooth muscle cells in culture and in acutely injured arteries, thus protecting against inflammation-induced vascular injury.


Assuntos
Anti-Inflamatórios/farmacologia , Lesões das Artérias Carótidas/prevenção & controle , Proteínas de Ligação a DNA/metabolismo , Glucosamina/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , NF-kappa B/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Acetilglucosamina/metabolismo , Animais , Anti-Inflamatórios/metabolismo , Lesões das Artérias Carótidas/genética , Lesões das Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/patologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Glucosamina/metabolismo , Glicosilação , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Neointima , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética
19.
Cytoskeleton (Hoboken) ; 75(2): 70-84, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29236364

RESUMO

Intraflagellar transport (IFT) is a conserved mechanism essential for the assembly and maintenance of most eukaryotic cilia and flagella. However, little is known about its role in sperm flagella formation and male fertility. IFT140 is a component of IFT-A complex. In mouse, it is highly expressed in the testis. Ift140 gene was inactivated specifically in mouse spermatocytes/spermatids. The mutant mice did not show any gross abnormalities, but all were infertile and associated with significantly reduced sperm number and motility. Multiple sperm morphological abnormalities were discovered, including amorphous heads, short/bent flagella and swollen tail tips, as well as vesicles along the flagella due to spermiogenesis defects. The epididymides contained round bodies of cytoplasm derived from the sloughing of the cytoplasmic lobes and residual bodies. Knockout of Ift140 did not significantly affect testicular expression levels of selective IFT components but localization of IFT27 and IFT88, two components of IFT-B complex, was changed. Our findings demonstrate that IFT140 is a key regulator for male fertility and normal spermiogenesis in mice. It not only plays a role in sperm flagella assembling, but is also involved in critical assembly of proteins that interface between the germ cell plasma and the Sertoli cell.


Assuntos
Proteínas de Transporte/metabolismo , Fertilidade/fisiologia , Cauda do Espermatozoide/metabolismo , Espermátides/metabolismo , Espermatócitos/metabolismo , Espermatogênese/fisiologia , Animais , Proteínas de Transporte/genética , Masculino , Camundongos , Camundongos Knockout , Células de Sertoli/metabolismo , Espermátides/citologia , Espermatócitos/citologia
20.
Dev Biol ; 432(1): 125-139, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-28964737

RESUMO

Intraflagellar transport (IFT) is an evolutionarily conserved mechanism essential for the assembly and maintenance of most eukaryotic cilia and flagella. In mice, mutations in IFT proteins have been shown to cause several ciliopathies including retinal degeneration, polycystic kidney disease, and hearing loss. However, little is known about its role in the formation of the sperm tail, which has the longest flagella of mammalian cells. IFT27 is a component of IFT-B complex and binds to IFT25 directly. In mice, IFT27 is highly expressed in the testis. To investigate the role of IFT27 in male germ cells, the floxed Ift27 mice were bred with Stra8-iCre mice so that the Ift27 gene was disrupted in spermatocytes/spermatids. The Ift27: Stra8-iCre mutant mice did not show any gross abnormalities, and all of the mutant mice survived to adulthood. There was no difference between testis weight/body weight between controls and mutant mice. All adult homozygous mutant males examined were completely infertile. Histological examination of the testes revealed abnormally developed germ cells during the spermiogenesis phase. The epididymides contained round bodies of cytoplasm. Sperm number was significantly reduced compared to the controls and only about 2% of them remained significantly reduced motility. Examination of epididymal sperm by light microscopy and SEM revealed multiple morphological abnormalities including round heads, short and bent tails, abnormal thickness of sperm tails in some areas, and swollen tail tips in some sperm. TEM examination of epididymal sperm showed that most sperm lost the "9+2″ axoneme structure, and the mitochondria sheath, fibrous sheath, and outer dense fibers were also disorganized. Some sperm flagella also lost cell membrane. Levels of IFT25 and IFT81 were significantly reduced in the testis of the conditional Ift27 knockout mice, and levels of IFT20, IFT74, and IFT140 were not changed. Sperm lipid rafts, which were disrupted in the conditional Ift25 knockout mice, appeared to be normal in the conditional Ift27 knockout mice. Our findings suggest that like IFT25, IFT27, even though not required for ciliogenesis in somatic cells, is essential for sperm flagella formation, sperm function, and male fertility in mice. IFT25 and IFT27 control sperm formation/function through many common mechanisms, but IFT25 has additional roles beyond IFT27.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Espermatogênese/fisiologia , Proteínas rab de Ligação ao GTP/fisiologia , Animais , Axonema/metabolismo , Transporte Biológico , Diferenciação Celular/fisiologia , Cílios/metabolismo , Fertilidade/fisiologia , Flagelos/metabolismo , Flagelos/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Camundongos , Camundongos Knockout , Ligação Proteica , Espermatozoides/metabolismo , Espermatozoides/fisiologia , Testículo/metabolismo , Testículo/fisiologia , Proteínas rab de Ligação ao GTP/metabolismo
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