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1.
J Asian Nat Prod Res ; : 1-9, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38509703

RESUMEN

Thrombosis plays an important role in the occurrence and development of cardiovascular and cerebrovascular diseases that contribute to high mortality and morbidity in patients. L-(-)-Quebrachitol (QCT), a natural product, was first isolated from quebracho bark. It can inhibit PAF receptor and decrease gastric damage induced by indomethacin, as a drug against platelet aggregation. Here, five QCT derivatives were synthesized and investigated for their inhibitory effects on platelet aggregation. Among them, compound 3a showed anticoagulant effects comparable to aspirin, while compound 4b showed dose-independent inhibitory activities in rats that were stronger than aspirin.

2.
Front Neurosci ; 18: 1374567, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38533446

RESUMEN

Objective: To explore the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cognitive impairment in Parkinson's disease (PD-CI). Methods: A case-control study involving 100 hospitalized PD patients and 60 healthy controls was carried out. Serum Lp-PLA2 level was detected by automatic biochemical analyzer. Based on whether Parkinson's patients have cognitive impairment, PD patients were subdivided to analyze the clinical value of Lp-PLA2. Relationship between Lp-PLA2 and PD-CI risk was analyzed by logistic regression. Diagnostic value of Lp-PLA2 in PD-CI patients was investigated using receiver's operator characteristic curves. Results: The levels of serum Lp-PLA2 activity in Parkinson's disease with normal cognition (PD-NC) and PD-CI patients were significantly higher than those in healthy controls (HCs), respectively. Furthermore, compared to the PD-NC group, the serum Lp-PLA2 activity level was significantly higher in PD-CI patients. Multivariable logistic regression analysis indicated that higher Lp-PLA2 level was an independent risk factor for PD patients with cognitive impairment. Moreover, the area under the efficacy curve of Lp-PLA2 for predicting PD-CI is 0.659. Conclusion: Our study shows that higher levels of Lp-PLA2 activity in PD patients are associated with the risk of developing cognitive impairment. Therefore, given the wide availability, safety, and convenience of monitoring serum Lp-PLA2 activity, it may serve as an early biomarker for cognitive impairment in PD patients.

3.
Medicine (Baltimore) ; 102(50): e36608, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38115302

RESUMEN

BACKGROUND: This study aimed to explore the value of tumor-infiltrating Forkhead box P3(FoxP3+) regulatory T cells (Tregs) in evaluating the prognosis of biliary tract cancer. METHODS: Four electronic databases were searched using 2 computers: PubMed, Embase, Web of Science, and Cochrane Library. The vocabulary and syntax were adapted according to the database. Two researchers independently selected the studies, collected information, and assessed the risk of bias. The Meta-analysis was performed using STATA 17.0, and HR and its corresponding 95% CI were used to evaluate the correlation between FoxP3+ Tregs and the overall survival of patients with biliary tract cancer. In addition, the quality of the included studies was evaluated. RESULTS: Ten articles were included in this study. The results of the meta-analysis showed that patients with high FoxP3+ Tregs infiltration had worse overall survival (OS) (HR = 1.34,95% CI 1.16 to 1.71; P < .001). Subgroup analysis of gallbladder carcinoma and cholangiocarcinoma showed that the high infiltration of FoxP3+ Tregs was significantly correlated with the OS of the former (HR = 1.55,95% CI 1.11 to 2.00; P < .001), but not with the OS of the latter (HR = 1.00,95% CI 0.62 to 1.38; P > .05). CONCLUSIONS: Our meta-analysis reveals that high infiltration of FoxP3 + Tregs is significantly associated with reduced overall survival in gallbladder carcinoma, endorsing their use as a prognostic biomarker for this subtype. In contrast, no significant prognostic correlation was identified for FoxP3+ Tregs in cholangiocarcinoma, indicating the need for subtype-specific evaluation of their prognostic relevance in biliary tract cancers.


Asunto(s)
Neoplasias de los Conductos Biliares , Neoplasias del Sistema Biliar , Colangiocarcinoma , Neoplasias de la Vesícula Biliar , Humanos , Pronóstico , Linfocitos T Reguladores , Factores de Transcripción Forkhead , Linfocitos Infiltrantes de Tumor , Conductos Biliares Intrahepáticos
4.
Cell Rep ; 42(9): 113028, 2023 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-37632748

RESUMEN

Biliary epithelial cells (BECs) are a potential source to repair the damaged liver when hepatocyte proliferation is compromised. Promotion of BEC-to-hepatocyte transdifferentiation could be beneficial to the clinical therapeutics of patients with end-stage liver diseases. However, mechanisms underlying the initiation of BEC transdifferentiation remain largely unknown. Here, we show that upon extreme hepatocyte injury, vegfaa and vegfr2/kdrl are notably induced in hepatic stellate cells and BECs, respectively. Pharmacological and genetic inactivation of vascular endothelial growth factor (VEGF) signaling would disrupt BEC dedifferentiation and proliferation, thus restraining hepatocyte regeneration. Mechanically, VEGF signaling regulates the activation of the PI3K-mammalian target of rapamycin complex 1 (mTORC1) axis, which is essential for BEC-to-hepatocyte transdifferentiation. In mice, VEGF signaling exerts conserved roles in oval cell activation and BEC-to-hepatocyte differentiation. Taken together, this study shows VEGF signaling as an initiator of biliary-mediated liver regeneration through activating the PI3K-mTORC1 axis. Modulation of VEGF signaling in BECs could be a therapeutic approach for patients with end-stage liver diseases.


Asunto(s)
Hepatopatías , Factor A de Crecimiento Endotelial Vascular , Humanos , Animales , Ratones , Fosfatidilinositol 3-Quinasas , Regeneración Hepática/fisiología , Hepatocitos , Proliferación Celular , Diana Mecanicista del Complejo 1 de la Rapamicina , Hígado , Mamíferos
5.
Micromachines (Basel) ; 13(9)2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-36144070

RESUMEN

Accelerometers based on outputting amplitude ratios in weakly coupled resonators (WCRs) are attractive because their parametric sensitivity is higher by two or three orders of magnitudes than those based on outputting frequency. However, the impact of temperature on the coupler is a key factor in accelerometer applications. This paper proposed a novel mode-localized WCR accelerometer with a temperature compensation mechanism, with sensitive elements incorporating a double-ended tuning fork (DETF) resonator, clamped-clamped (CC) resonator, and a micro-lever coupler. The DETF out-of-phase mode is utilized, which is only sensitive to temperature, to measure the temperature change of WCRs and complete the temperature compensation using the compensation algorithm. This proposed method has no time delay in measuring the temperature of sensitive elements and no temperature difference caused by the uneven temperature field. The parametric sensitivity in amplitude ratio (AR) to acceleration drifting with temperature was theoretically analyzed, and the novel device was designed and fabricated by a silicon-on-glass process. Both simulation and experiment results demonstrated that the coupling stiffness drifted with temperature, which resulted in the drifts of its sensitivity to acceleration and zero-bias stability. Using the intrinsic mode of WCRs, in terms of the DETF out-of-phase mode, as an in situ thermometer and carrying out the temperature compensation algorithm, the drift of zero bias could be suppressed from 102 mg to 4.5 mg (g is the gravity acceleration), and the drift of the parameter sensitivity in AR was suppressed from 0.74 AR/g to 0.02 AR/g with the temperature range from 330 K to 370 K and acceleration range from 0 g to 0.2 g.

6.
Phys Chem Chem Phys ; 24(23): 14517-14524, 2022 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-35665786

RESUMEN

Electrochemical reduction of nitrogen is considered a promising route for achieving green and sustainable ammonia synthesis under ambient conditions. A transition metal atom loaded on N-doped graphene is commonly used in the nitrogen reduction reaction (NRR), but the effect of the graphene's coordination environment on electron transfer has rarely been studied. Herein, the NRR performance of Fe1/2/3 clusters, anchored on single-vacancy and N-doped graphene, is investigated systematically via density functional theory (DFT). The calculation results show that the Fe2 cluster supported by two N atom-modified single-vacancy graphene displays the highest catalytic performance of NRR with the lowest energy barrier of 0.62 eV among the 12 candidates, and exhibits efficient selectivity. It has superior performance because of the highly asymmetrical distribution of electrons on graphene, the large positive charge of the Fe2, and the strong adsorption of *NNH. This study provides a new strategy to improve the NRR performance by regulating the Fe1/2/3 clusters coordination environment.

7.
Hepatol Int ; 16(4): 954-963, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35729470

RESUMEN

PURPOSE: We aimed to assess the dynamic changing trend of serum matrix metalloproteinase-7 (MMP-7) in biliary atresia (BA) patients from diagnosis to LTx to further elucidate its clinical value in diagnosis and prognoses and its relationship with disease progression. METHODS: In this multicentre prospective study, 440 cholestasis patients (direct bilirubin level of > 17 µmol/L) were enrolled. Serum MMP-7 levels were measured using an enzyme-linked immunosorbent assay at diagnosis, 1 week, 2 weeks, 1 month, 6 weeks, 2 months, 3 months, 6 months and then every 6 months post-KPE. The medical record at each follow-up visit for post-Kasai portoenterostomy patient was collected and analyzed. RESULTS: Using a cut-off value of > 26.73 ng/mL, serum MMP-7 had an AUC of 0.954 in BA neonates and 0.983 in BA infants. A genetic mutation (G137D) was associated with low MMP-7 levels in serum of BA patients. MMP-7 showed a mediation effect on the association between inflammation and liver fibrosis in BA patients. Four dynamic patterns of serum MMP-7 post-KPE were associated with prognosis. Serum MMP-7 was the only significant predictor at 6 weeks post-KPE and the most accurate predictor at 3 months post-KPE of survival with the native liver in 2 years. CONCLUSION: As one of the critical factors associated with BA occurrence and progression, serum MMP-7 can be used for early diagnosis of BA and post-KPE MMP-7 level is the earliest prognostic biomarker so far.


Asunto(s)
Atresia Biliar , Metaloproteinasa 7 de la Matriz , Atresia Biliar/diagnóstico , Progresión de la Enfermedad , Humanos , Lactante , Recién Nacido , Metaloproteinasa 7 de la Matriz/sangre , Portoenterostomía Hepática , Estudios Prospectivos , Resultado del Tratamiento
8.
Micromachines (Basel) ; 13(4)2022 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-35457906

RESUMEN

Nowadays, accurate and robust localization is preliminary for achieving a high autonomy for robots and emerging applications. More and more, sensors are fused to guarantee these requirements. A lot of related work has been developed, such as visual-inertial odometry (VIO). In this research, benefiting from the complementary sensing capabilities of IMU and cameras, many problems have been solved. However, few of them pay attention to the impact of different performance IMU on the accuracy of sensor fusion. When faced with actual scenarios, especially in the case of massive hardware deployment, there is the question of how to choose an IMU appropriately? In this paper, we chose six representative IMUs with different performances from consumer-grade to tactical grade for exploring. According to the final performance of VIO based on different IMUs in different scenarios, we analyzed the absolute trajectory error of Visual-Inertial Systems (VINS_Fusion). The assistance of IMU can improve the accuracy of multi-sensor fusion, but the improvement of fusion accuracy with different grade MEMS-IMU is not very significant in the eight experimental scenarios; the consumer-grade IMU can also have an excellent result. In addition, the IMU with low noise is more versatile and stable in various scenarios. The results build the route for the development of Inertial Navigation System (INS) fusion with visual odometry and at the same time, provide a guideline for the selection of IMU.

9.
Micromachines (Basel) ; 13(3)2022 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-35334729

RESUMEN

Mode-localized sensing paradigms applied to accelerometers have recently become popular research subjects. However, the output of mode-localized accelerometers is influenced by environment temperature due to the difference in the thermal properties of the coupling resonators and the temperature dependence of coupling stiffness. To improve the performance of mode-localized accelerometers against temperature, we proposed an in situ self-temperature compensation method by utilizing the resonant frequency besides of amplitude ratios, which can be implied online. Experimental results showed that there were nearly 79-times and 87-times improvement in zeros bias and scale factor, respectively.

10.
Micromachines (Basel) ; 12(9)2021 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-34577666

RESUMEN

Resonant accelerometers are promising because of their wide dynamic range and long-term stability. With quasi-digital frequency output, the outputs of resonant accelerometers are less vulnerable to the noise from circuits and ambience. Differential structure is usually adopted in a resonant accelerometer to achieve higher sensitivity to acceleration and to reduce common noise at the same time. Ideally, a resonant accelerometer is only sensitive to external acceleration. However, temperature has a great impact on resonant accelerometers, causing unexcepted frequency drift. In order to cancel out the frequency drift caused by temperature change, an improved temperature compensation method for differential vibrating accelerometers without additional temperature sensors is presented in this paper. Experiment results demonstrate that the temperature sensitivity of the prototype sensor is reduced from 43.16 ppm/°C to 0.83 ppm/°C within the temperature range of -10 °C to 70 °C using the proposed method.

11.
Hepatology ; 74(6): 3345-3361, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34320243

RESUMEN

BACKGROUND AND AIMS: Liver regeneration after extreme hepatocyte loss occurs through transdifferentiation of biliary epithelial cells (BECs), which includes dedifferentiation of BECs into bipotential progenitor cells (BPPCs) and subsequent redifferentiation into nascent hepatocytes and BECs. Although multiple molecules and signaling pathways have been implicated to play roles in the BEC-mediated liver regeneration, mechanisms underlying the dedifferentiation-redifferentiation transition and the early phase of BPPC redifferentiation that is pivotal for both hepatocyte and BEC directions remain largely unknown. APPROACH AND RESULTS: The zebrafish extreme liver damage model, genetic mutation, pharmacological inhibition, transgenic lines, whole-mount and fluorescent in situ hybridizations and antibody staining, single-cell RNA sequencing, quantitative real-time PCR, and heat shock-inducible overexpression were used to investigate roles and mechanisms of farnesoid X receptor (FXR; encoded by nuclear receptor subfamily 1, group H, member 4 [nr1h4]) in regulating BPPC redifferentiation. The nr1h4 expression was significantly up-regulated in response to extreme liver injury. Genetic mutation or pharmacological inhibition of FXR was ineffective to BEC-to-BPPC dedifferentiation but blocked the redifferentiation of BPPCs to both hepatocytes and BECs, leading to accumulation of undifferentiated or less-differentiated BPPCs. Mechanistically, induced overexpression of extracellular signal-related kinase (ERK) 1 (encoded by mitogen-activated protein kinase 3) rescued the defective BPPC-to-hepatocyte redifferentiation in the nr1h4 mutant, and ERK1 itself was necessary for the BPPC-to-hepatocyte redifferentiation. The Notch activities in the regenerating liver of nr1h4 mutant attenuated, and induced Notch activation rescued the defective BPPC-to-BEC redifferentiation in the nr1h4 mutant. CONCLUSIONS: FXR regulates BPPC-to-hepatocyte and BPPC-to-BEC redifferentiations through ERK1 and Notch, respectively. Given recent applications of FXR agonists in the clinical trials for liver diseases, this study proposes potential underpinning mechanisms by characterizing roles of FXR in the stimulation of dedifferentiation-redifferentiation transition and BPPC redifferentiation.


Asunto(s)
Regeneración Hepática , Glicoproteínas de Membrana Plaquetaria/fisiología , Células Madre/fisiología , Animales , Sistema Biliar/citología , Diferenciación Celular , Regeneración Hepática/fisiología , Reacción en Cadena en Tiempo Real de la Polimerasa , Pez Cebra
12.
Appl Opt ; 60(2): 291-295, 2021 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-33448951

RESUMEN

A large number of space activities are generating a high amount of undesirable space debris, which causes inevitable damage to spacecraft and satellites. Moreover, the damage assessment of ultrahigh-speed debris is a challenging task that requires both theoretical and ground-level experimental simulations. One should note that the location and damage degree can be preliminarily determined by measuring the impact flash spectrum, which provides basic data for damage assessment. Herein, the radiation spectrum of an ultrahigh-speed collision between plastic projectile and aluminum target is measured by using spectroscopic technology. The surface temperature of the colliding material, electron temperature, and electron density in the plasma are simultaneously retrieved by using a single-frame spectrum. The single-frame spectrum is separated into a continuous spectrum and a line spectrum by using continuous thermal radiation spectrum inversion material interface temperature and line spectrum inversion electron temperature and electron density in the plasma.

13.
BMC Infect Dis ; 20(1): 698, 2020 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-32962655

RESUMEN

BACKGROUND: A new coronavirus disease 2019 (COVID-19) has escalated to a pandemic since its first outbreak in Wuhan, China. A small proportion of patients may have difficulty in generating IgM or IgG antibodies against SARS-CoV-2, and little attention has been paid to them. CASE PRESENTATIONS: We present two cases of confirmed COVID-19 patients and characterize their initial symptoms, chest CT results, medication, and laboratory test results in detail (including RT-PCR, IgM/ IgG, cytokine and blood cell counts). CONCLUSION: Both of patients with confirmed COVID-19 pneumonia failed to produce either IgM or IgG even 40 to 50 days after their symptoms onset. This work provides evidence demonstrating that at least a small proportion of patients may have difficulty in rapidly gaining immunity against SARS-CoV-2.


Asunto(s)
Anticuerpos Antivirales/sangre , Infecciones por Coronavirus/diagnóstico , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Neumonía Viral/diagnóstico , Adulto , Betacoronavirus , COVID-19 , Prueba de COVID-19 , China/epidemiología , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/inmunología , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/inmunología , SARS-CoV-2
14.
Appl Opt ; 59(10): 3102-3108, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32400592

RESUMEN

Accurate measurement of temperature and distance is essential for applications in multiple fields such as air defense, antimissile systems, laser damage, and infrared remote sensing. However, ranging currently relies on either laser or infrared radiation characteristics, neither of which fully utilize the substantial information contained in the spectrum. In this study, we realized the simultaneous inversion of target radiant temperature and distance via spectrum separation based on the distance information from the atmospheric spectrum as well as the temperature information from multispectral radiation thermometry (MRT), by measuring the thermal radiation spectrum of distant high-temperature objects. The study initially involved conducting a theoretical analysis of long-distance MRT in the atmosphere by utilizing the least squares and Newton's iteration methods. Once the thermal radiation spectrum and the long-distance atmospheric spectral transmittance were acquired from nonlinear models, highly precise and accurate radiant temperature and distance information was derived via simultaneous inversion. Subsequently, experimental verifications were performed to measure an explosion spectrum at a temperature of approximately 2000 K and a distance of 9 km. The spectral band was 400-900 nm, and the temperature and distance of the explosion calculated by the inversion was 2004.4 K and 9.9 km, respectively. The inversion distance error was 10%, indicating that the simultaneous inversion of radiant temperature and distance was successful and that the proposed method was effective. The method proposed in this study can be applied to the measurement of radiant temperature and distance of long-distance objects.

15.
J Med Virol ; 92(10): 2050-2054, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32383183

RESUMEN

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019 has spread throughout the world and caused many thousands of deaths. The previous study reported a higher severe status rate and mortality rate in male patients in China. However, the reason underlying this difference has not been reported. The convalescent plasma containing a high level of SARS-CoV-2 immunoglobulin G (IgG) antibody has been used in clinical therapy and achieved good effects in China. In this study, to compare the differences of the SARS-CoV-2 IgG antibody between male and female patients, a total number of 331 patients confirmed SARS-CoV-2 infection were enrolled. The serum of these patients was collected during hospitalization and detected for the SARS-CoV-2 IgG antibody. Our data showed that the concentration of IgG antibody in mild, general, and recovering patients showed no difference between male and female patients. In severe status, compared with male patients, there were more female patients having a relatively high concentration of serum SARS-CoV-2 IgG antibody. In addition, the generation of IgG antibody in female patients was stronger than male patients in disease early phase. Our study identified a discrepancy in the SARS-CoV-2 IgG antibody level in male and female patients, which may be a potential cause leading to a different outcome of Coronavirus Disease 2019 between sex.


Asunto(s)
Anticuerpos Antivirales/sangre , COVID-19/epidemiología , COVID-19/terapia , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Pandemias , SARS-CoV-2/patogenicidad , Adulto , COVID-19/sangre , COVID-19/inmunología , COVID-19/mortalidad , China/epidemiología , Femenino , Hospitalización , Humanos , Inmunización Pasiva , Masculino , Persona de Mediana Edad , SARS-CoV-2/inmunología , Índice de Severidad de la Enfermedad , Factores Sexuales , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Sueroterapia para COVID-19
16.
Clin Infect Dis ; 71(8): 1930-1934, 2020 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-32306047

RESUMEN

BACKGROUND: The coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been rapidly spreading nationwide and abroad. A serologic test to identify antibody dynamics and response to SARS-CoV-2 was developed. METHODS: The antibodies against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19 at 3-40 days after symptom onset. The gold standard for COVID-19 diagnosis was nucleic acid testing for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction (rRT-PCR). The serodiagnostic power of the specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against SARS-CoV-2 was investigated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and consistency rate. RESULTS: The seroconversion of specific IgM and IgG antibodies were observed as early as the fourth day after symptom onset. In the patients with confirmed COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 77.3% (51/66), 100%, 100%, 80.0%, and 88.1%, respectively, and those of IgG were 83.3% (55/66), 95.0%, 94.8%, 83.8%, and 88.9%. In patients with suspected COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 87.5% (21/24), 100%, 100%, 95.2%, and 96.4%, respectively, and those of IgG were 70.8% (17/24), 96.6%, 85.0%, 89.1%, and 88.1%. Both antibodies performed well in serodiagnosis for COVID-19 and rely on great specificity. CONCLUSIONS: The antibodies against SARS-CoV-2 can be detected in the middle and later stages of the illness. Antibody detection may play an important role in the diagnosis of COVID-19 as a complementary approach to viral nucleic acid assays.


Asunto(s)
Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Ensayo de Inmunoadsorción Enzimática/métodos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Neumonía Viral/diagnóstico , Adulto , Anciano , Betacoronavirus/inmunología , COVID-19 , Prueba de COVID-19 , Estudios de Casos y Controles , Infecciones por Coronavirus/sangre , Femenino , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/sangre , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2 , Sensibilidad y Especificidad , Factores de Tiempo
17.
Int Immunopharmacol ; 73: 64-71, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31082724

RESUMEN

It is thought that autoantibody (aAb) production can be caused by (aberrant) protein targeting to the plasma surface of cells. We recently demonstrated the presence of the human cytochrome P450 enzyme CYP4Z1 on the plasma membrane of MCF-7 breast cancer cells and the detection of high titers of anti-CYP4Z1 aAbs in breast cancer patients, but not in healthy controls. In the present study we show that cells of the normal breast cell line MCF-10A do not display CYP4Z1 on their surface. By contrast, we detected CYP19A1 (aromatase) on the plasma membrane of both cell lines. Interestingly, the presence of CYPs on the cell surface did not correlate with their relative expression levels in these cell lines. Indirect ELISA experiments demonstrated the presence of anti-CYP19A1 aAbs in female breast cancer patient sera as well as in male and female controls, respectively; aAb titers in all three groups varied considerably and overall, the results obtained for each group were not significantly different from those of either of the other two groups. Based on these data we propose the hypothesis that CYP translocation to the plasma membrane, but not the intracellular expression level, is the crucial precondition for the generation of anti-CYP aAbs.


Asunto(s)
Aromatasa/inmunología , Aromatasa/metabolismo , Autoanticuerpos/sangre , Neoplasias de la Mama , Membrana Celular/enzimología , Familia 4 del Citocromo P450/metabolismo , Adulto , Anciano , Mama/enzimología , Mama/inmunología , Neoplasias de la Mama/sangre , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/inmunología , Línea Celular , Femenino , Humanos , Masculino , Persona de Mediana Edad
18.
Hepatology ; 70(6): 2092-2106, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31136010

RESUMEN

The liver has a high regenerative capacity. Upon two-thirds partial hepatectomy, the hepatocytes proliferate and contribute to liver regeneration. After severe liver injury, when the proliferation of residual hepatocytes is blocked, the biliary epithelial cells (BECs) lose their morphology and express hepatoblast and endoderm markers, dedifferentiate into bipotential progenitor cells (BP-PCs), then proliferate and redifferentiate into mature hepatocytes. Little is known about the mechanisms involved in the formation of BP-PCs after extreme liver injury. Using a zebrafish liver extreme injury model, we found that mammalian target of rapamycin complex 1 (mTORC1) signaling regulated dedifferentiation of BECs and proliferation of BP-PCs. mTORC1 signaling was up-regulated in BECs during extreme hepatocyte ablation and continuously expressed in later liver regeneration. Inhibition of mTORC1 by early chemical treatment before hepatocyte ablation blocked the dedifferentiation from BECs into BP-PCs. Late mTORC1 inhibition after liver injury reduced the proliferation of BP-PC-derived hepatocytes and BECs but did not affect BP-PC redifferentiation. mTOR and raptor mutants exhibited defects in BEC transdifferentiation including dedifferentiation, BP-PC proliferation, and redifferentiation, similar to the chemical inhibition. Conclusion: mTORC1 signaling governs BEC-driven liver regeneration by regulating the dedifferentiation of BECs and the proliferation of BP-PC-derived hepatocytes and BECs.


Asunto(s)
Sistema Biliar/citología , Desdiferenciación Celular , Regeneración Hepática/fisiología , Diana Mecanicista del Complejo 1 de la Rapamicina/fisiología , Células Madre/citología , Animales , Apoptosis , Proliferación Celular , Células Epiteliales/citología , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Proteínas Nucleares/fisiología , Transducción de Señal/fisiología , Sirolimus/farmacología , Pez Cebra , Proteínas de Pez Cebra/fisiología
19.
Biosci Rep ; 38(6)2018 12 21.
Artículo en Inglés | MEDLINE | ID: mdl-30120100

RESUMEN

Objective: To explore whether aspirin (ASA) enhances the sensitivity of hepatocellular carcinoma (HCC) side population (SP) cells to doxorubicin (Doxo) via miR-491/ATP-binding cassette sub-family G member 2 (ABCG2).Methods: Non-SP and SP cells were isolated from MHCC-97L cell line using flow cytometry analysis and fluorescence-activated cell sorting. Colony formation assay was performed to determine the colony-formation ability of cells. Cell viability of SP cells was determined with the MTT assay. Luciferase reporter assay was applied in confirming the binding between miR-491 and ABCG2.Results: Although the Doxo treatment lowered the colony-formation ability of both non-SP and SP cells, the colony-formation ability of SP cells was 2-fold higher than that of non-SP cells (P<0.05). Doxo slightly inhibited the cell viability of SP cells in a concentration-dependent manner; the addition of ASA dramatically enhanced the inhibitory effect of Doxo on SP cell viability in a concentration-dependent manner (P<0.05). Compared with non-SP cells, the miR-491 expression was significantly decreased in SP cells, which was significantly reversed by ASA (P<0.05). miR-491 directly controlled the ABCG2 expression. In the presence of Doxo, miR-491 inhibitor reduced the inhibitory effect of ASA on the cell viability of SP cells, which was significantly reversed by knockdown of ABCG2 (P<0.05).Conclusion: ASA enhanced the sensitivity of SP cells to Doxo via regulating the miR-491/ABCG2 signaling pathway.


Asunto(s)
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Aspirina/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , MicroARNs/genética , Proteínas de Neoplasias/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Doxorrubicina/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Hepáticas/patología , Células Madre Neoplásicas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
20.
Biochem Biophys Res Commun ; 497(2): 776-782, 2018 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-29470984

RESUMEN

Ribosome biogenesis is a significant process in cells. Dysfunction in this process will result in the defects of protein synthesis and consequently cause the development of specific diseases called ribosomopathies. Mutations in ribosome biogenesis protein Rps19, Rpl5, or Rpl11 can lead to hematopoietic defects in human, thus triggering the disease Diamond Blackfan anemia. However, the regulatory mechanisms of ribosome biogenesis in hematopoiesis remain incompletely understood. In this study, we describe a zebrafish mutant cq42, which carries a nonsense mutation in the gene that encodes ribosome biogenesis 2 homolog (Urb2). Urb2 is strongly expressed in the caudal hematopoietic tissue (CHT) during hematopoietic stem cells (HSCs) expanding. Molecular characterization of urb2cq42 larvae suggest that urb2 deficiency notably decrease the population of HSCs in CHT and early T cells in thymus. Further analysis shows that compromised cell proliferation and superfluous apoptosis are observed in the CHT of urb2cq42 mutant. P53 pathway is upregulated in the urb2cq42 larvae and loss-of-function of P53 can fully rescue the hematopoietic defects in urb2cq42 mutant. These data demonstrate that urb2 is essential for HSCs development through the regulation of P53 pathway.


Asunto(s)
Hematopoyesis , Células Madre Hematopoyéticas/citología , Proteínas Nucleares/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteínas de Pez Cebra/metabolismo , Pez Cebra/fisiología , Animales , Apoptosis , Sistemas CRISPR-Cas , Ciclo Celular , Marcación de Gen , Células Madre Hematopoyéticas/metabolismo , Mutación , Proteínas Nucleares/genética , Transducción de Señal , Pez Cebra/genética , Proteínas de Pez Cebra/genética
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