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1.
Nature ; 626(8001): 999-1004, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38418915

RESUMEN

The advantage of 3D printing-that is, additive manufacturing (AM) of structural materials-has been severely compromised by their disappointing fatigue properties1,2. Commonly, poor fatigue properties appear to result from the presence of microvoids induced by current printing process procedures3,4. Accordingly, the question that we pose is whether the elimination of such microvoids can provide a feasible solution for marked enhancement of the fatigue resistance of void-free AM (Net-AM) alloys. Here we successfully rebuild an approximate void-free AM microstructure in Ti-6Al-4V titanium alloy by development of a Net-AM processing technique through an understanding of the asynchronism of phase transformation and grain growth. We identify the fatigue resistance of such AM microstructures and show that they lead to a high fatigue limit of around 1 GPa, exceeding the fatigue resistance of all AM and forged titanium alloys as well as that of other metallic materials. We confirm the high fatigue resistance of Net-AM microstructures and the potential advantages of AM processing in the production of structural components with maximum fatigue strength, which is beneficial for further application of AM technologies in engineering fields.

2.
J Biol Chem ; 298(11): 102571, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36209822

RESUMEN

The REGγ-20S proteasome is an ubiquitin- and ATP-independent degradation system, targeting selective substrates, possibly helping to regulate aging. The studies we report here demonstrate that aging-associated REGγ decline predisposes to decreasing tau turnover, as in a tauopathy. The REGγ proteasome promotes degradation of human and mouse tau, notably phosphorylated tau and toxic tau oligomers that shuttle between the cytoplasm and nuclei. REGγ-mediated proteasomal degradation of tau was validated in 3- to 12-month-old REGγ KO mice, REGγ KO;PS19 mice, and PS19 mice with forebrain conditional neuron-specific overexpression of REGγ (REGγ OE) and behavioral abnormalities. Coupled with tau accumulation, we found with REGγ-deficiency, neuron loss, dendrite reduction, tau filament accumulation, and microglial activation are much more prominent in the REGγ KO;PS19 than the PS19 model. Moreover, we observed that the degenerative neuronal lesions and aberrant behaviors were alleviated in REGγ OE;PS19 mice. Memory and other behavior analysis substantiate the role of REGγ in prevention of tauopathy-like symptoms. In addition, we investigated the potential mechanism underlying aging-related REGγ decline. This study provides valuable insights into the novel regulatory mechanisms and potential therapeutic targets for tau-related neurodegenerative diseases.


Asunto(s)
Complejo de la Endopetidasa Proteasomal , Tauopatías , Humanos , Animales , Ratones , Lactante , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Tauopatías/genética , Autoantígenos/metabolismo , Citoplasma/metabolismo , Envejecimiento/genética
3.
Sensors (Basel) ; 23(19)2023 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-37837144

RESUMEN

Piezoelectric accurate actuation plays an important role in industrial applications. The intrinsic frequency of previous actuators is invariable. However, variable frequency can approach the range near the low-intrinsic-frequency and realize a high actuation capability. The frequency-variable linear and rotary motion (FVLRM) principle is proposed for rotor-blade-based two-degree-of-freedom driving. Inertial force is generated by frequency-variable piezoelectric oscillators (FVPO), the base frequency and vibration modes of which are adjustable by the changeable mass and position of the mass block. The variable-frequency principle of FVPO and the FVLRM are recognized and verified by the simulations and experiments, respectively. The experiments show that the FVLRM prototype moves the fastest when the mass block is placed at the farthest position and the prototype is at the second-order intrinsic frequencies of 42 Hz and 43 Hz, achieving a linear motion of 3.52 mm/s and a rotary motion of 286.9 mrad/s. The actuator adopts a lower operating frequency of less than 60 Hz and has the function of adjusting the natural frequency. It can achieve linear and rotational motion with a larger working stroke with 140 mm linear movement and 360° rotation.

4.
Zhonghua Nan Ke Xue ; 29(1): 49-53, 2023 Jan.
Artículo en Zh | MEDLINE | ID: mdl-37846832

RESUMEN

OBJECTIVE: To summarize the clinical experience in the treatment of sexual intercourse-related hematuria in males using biopsy forceps, electrocoagulation and holmium laser cauterization. METHODS: From July 2018 to April 2022, we treated 11 male patients with intercourse-related hematuria using biopsy forceps, electrocoagulation and holmium laser cauterization. The patients ranged in age from 29 to 47 years, with clinical manifestations of gross hematuria, blood dripping from the urethral orifice or blood clots in the urine after sexual intercourse or erection, 3 with hemospermia, but none with pain. All the patients received urological imaging examination to exclude lesions in the upper urinary tract and bladder preoperatively. During the operation, varicose vessels were found around the posterior urethral verumontanum under the cystourethroscope in all the cases, 5 with active bleeding in the posterior varicose vessel. The 3 cases with hemospermia first underwent trans-prostatic utricle seminal vesiculoscopy. According to the range and number of varicose vessels, 5 of the patients were treated by electrocoagulation with the resectoscope, 2 by holmium laser cauterization and the other 4 with biopsy forceps to destroy the vascular tissue. After the operation, urinary catheters were retained for 3-7 days, abstinence lasted 30 days, and the patients were followed up for 6 months. RESULTS: The operations were successfully completed in all the cases, 10 with good prognosis and none with recurrence. Occasional postoperative hematuria and blood clots in the urine were observed in 1 of the patients treated by electrocoagulation under the resectoscope, with dysuria at 3 months after operation, who underwent repeated electrocoagulation and experienced no more recurrence thereafter. Different degrees of postoperative urethral irritation and gross hematuria were found in all the cases, which spontaneously disappeared within 1-4 weeks, with no such complications as ED, ejaculation pain, ejaculation difficulty and ejaculation weakness. CONCLUSION: In the absence of other genitourinary diseases, painless hematuria, blood clots in the urine or even dysuria in males after sexual intercourse can be considered as the results of possible varicose veins around the posterior urethral verumontanum, which can be treated satisfactorily by destroying the vascular tissue with biopsy forceps, electrocoagulation with the resectoscope or holmium laser cauterization according to the location, number and degree of varicose veins.


Asunto(s)
Hematospermia , Trombosis , Várices , Humanos , Masculino , Adulto , Persona de Mediana Edad , Hematospermia/etiología , Coito , Hematuria/etiología , Disuria/complicaciones , Várices/complicaciones , Trombosis/complicaciones , Dolor
5.
Zhonghua Nan Ke Xue ; 29(5): 426-429, 2023 May.
Artículo en Zh | MEDLINE | ID: mdl-38602759

RESUMEN

OBJECTIVE: To analyze the causes of skin necrosis after penis lengthening surgery and corresponding treatment measures, and observe the clinical effect of free skin graft repair in the treatment of penile skin defects. METHODS: We retrospectively analyzed the clinical data on 12 cases of extensive penile skin necrosis and defect after penis lengthening surgery performed in our department from January 2017 to January 2022. The patients underwent free skin graft repair with medium- or full-thickness skin grafts from the thigh after wound preparation. RESULTS: The skin grafts survived well in all the 12 patients and the incisions healed in the first stage without any complications. At 6 months after surgery, skin sensation was mostly recovered in the area of penis skin grafting, no obvious skin ulceration or edema was observed, and the appearance of the penis was satisfactory. The IIEF-5 scores, Erectile Hardness Scale (EHS) scores, and the results of penile hardness tests of the patients all indicated normal erectile function. CONCLUSION: Free skin graft repair with autologous medium- or full-thickness skin grafts is a safe and effective surgical option for extensive penile skin necrosis after penis lengthening surgery.


Asunto(s)
Pene , Piel , Humanos , Masculino , Necrosis , Pelvis , Pene/cirugía , Estudios Retrospectivos
6.
Cell Mol Biol (Noisy-le-grand) ; 68(1): 51-58, 2022 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-35809328

RESUMEN

Approximately 85% of stroke patients suffer from ischemic stroke, which has a high incidence and difficult prognosis. It has become one of the leading causes of death in middle-aged and elderly people and seriously threatens human health. This study mainly considers the role of lncRNA tug 1 on the ERK 12 signaling pathway to enhance neuronal damage after acute ischemic stroke. In the experiment, the middle cerebral artery occlusion (MCAO) model was constructed using the thread embolization method. The real-time quantitative RT-CR method was used to detect the relative transcriptional activity of TG1, GAS5 and SM22a genes in tissues. The relative expression level of SM22a protein in tissues was detected by the immune-histochemical method. Twenty-four hours after cerebral infarction, the nerve function, cerebral infarction area and ERK1/2 protein expression level of cerebral cortex on the side of cerebral infarction were detected in each group. The experimental results showed that the successful animal behavior scores of the MCAO model in the normal saline control group and Pepstatin A interference group were 1 point 25, 2 points 17 and 3 points 18. The results show that lncRNA tug1 can enhance the neuronal damage of the ERK12 signaling pathway after acute ischemic stroke. lncRNATUGl plays an important role after OGD/RX and can accelerate cell apoptosis. If the expression of lncRNATUGl is inhibited, the number of apoptosis is significantly reduced.


Asunto(s)
Accidente Cerebrovascular Isquémico , ARN Largo no Codificante , Accidente Cerebrovascular , Anciano , Animales , Apoptosis/genética , Humanos , Infarto de la Arteria Cerebral Media/genética , Infarto de la Arteria Cerebral Media/metabolismo , Accidente Cerebrovascular Isquémico/genética , Persona de Mediana Edad , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Transducción de Señal , Accidente Cerebrovascular/genética
7.
Phytother Res ; 36(8): 3181-3201, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35794729

RESUMEN

Glycolysis is the primary source of energy for cancer growth and metastasis. The shift in metabolism from mitochondrial oxidative phosphorylation to aerobic glycolysis is called the Warburg effect. Cancer progression due to aerobic glycolysis is often associated with the activation of oncogenes or the loss of tumor suppressors. Therefore, inhibition of glycolysis is one of the effective strategies in cancer control. Pyruvate kinase M2 (PKM2) is a key glycolytic enzyme overexpressed in breast, prostate, lung, colorectal, and liver cancers. Here, we discuss published studies regarding PKM2 inhibitors from natural products that are promising drug candidates for cancer therapy. We have highlighted the potential of natural PKM2 inhibitors for various cancer types. Moreover, we encourage researchers to evaluate the combinational effects between natural and synthetic PKM2 inhibitors. Also, further high-quality studies are needed to firmly establish the clinical efficacy of natural products.


Asunto(s)
Productos Biológicos , Neoplasias , Productos Biológicos/metabolismo , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Línea Celular Tumoral , Glucólisis , Humanos , Mitocondrias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Piruvato Quinasa/metabolismo
8.
Can J Infect Dis Med Microbiol ; 2022: 1668703, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35979517

RESUMEN

Background: Infection with syphilis is still a major public health problem. The precise data for syphilis seroprevalence in the populations will help to develop a strategy for prevention and treatment of it. However, the data for syphilis prevalence in continuous years among volunteer blood donors in China is rare. Methods: A retrospective study for Treponema pallidum (TP) antibody in blood donors was conducted from January 2010 to December 2019 at the Blood Center of Zhejiang Province, China. TP antibody was detected with two different reagents using enzyme-linked immunosorbent assay and the only sample which was reactive in the two reagents was defined as seropositive. Results: A total of 992,646 volunteer blood donors were analyzed and the positive rate of TP antibody in the blood donors was 0.43%. From 2010 to 2019, the positive rates of TP antibody were 0.53%, 0.51%, 0.51%, 0.43%, 0.36%, 0.18%, 0.11%, 0.12%, 0.11%, and 0.10%, respectively. The positive rates of TP antibody were significantly different among blood donor age group (p < 0.001), with the highest positive rate in 45-54-years-old group (0.93%). The positive rates of TP antibody in male and female blood donors were 0.44% and 0.41%, respectively. The positive rate was 0.57% among the first-time blood donors, which was significantly higher than that of the repeat blood donors (0.17%). The positive rate of TP antibody in blood donors decreased gradually with the increase of educational level. Conclusion: The syphilis seroprevalence is low in the blood donors of the Hangzhou area, and the positive rate of blood donors is associated with age, educational level, and times of blood donation. Increasing the number of repeat blood donations is helpful to improve blood safety.

9.
BMC Cancer ; 21(1): 1267, 2021 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-34819038

RESUMEN

BACKGROUND: Bladder cancer (BC) is one of the most common malignancies and has a relatively poor outcome worldwide. In this study, we attempted to construct a novel metabolism-related gene (MRG) signature for predicting the survival probability of BC patients. METHODS: First, differentially expressed MRGs between BC and normal samples were identified and used to construct a protein-protein interaction (PPI) network and perform mutation analysis. Next, univariate Cox regression analysis was utilized to select prognostic genes, and multivariate Cox regression analysis was applied to establish an MRG signature for predicting the survival probability of BC patients. Moreover, Kaplan-Meier (KM) survival analysis and receiver operating characteristic (ROC) analysis were performed to evaluate the predictive capability of the MRG signature. Finally, a nomogram based on the MRG signature was established to better predict the survival of BC. RESULTS: In the present study, 27 differentially expressed MRGs were identified, most of which presented mutations in BC patients, and LRP1 showed the highest mutation rate. Next, an MRG signature, including MAOB, FASN and LRP1, was established by using univariate and multivariate Cox regression analysis. Furthermore, survival analysis indicated that BC patients in the high-risk group had a dramatically lower survival probability than those in the low-risk group. Finally, Cox regression analysis showed that the risk score was an independent prognostic factor, and a nomogram integrating age, pathological tumor stage and risk score was established and presented good predictive ability. CONCLUSION: We successfully constructed a novel MRG signature to predict the prognosis of BC patients, which might contribute to the clinical treatment of BC.


Asunto(s)
Perfilación de la Expresión Génica , Mutación , Mapas de Interacción de Proteínas/genética , Transcriptoma , Neoplasias de la Vejiga Urinaria/genética , Factores de Edad , Bases de Datos Genéticas , Acido Graso Sintasa Tipo I/genética , Femenino , Ontología de Genes , Humanos , Estimación de Kaplan-Meier , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Masculino , Persona de Mediana Edad , Monoaminooxidasa/genética , Nomogramas , Modelos de Riesgos Proporcionales , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patología
10.
Opt Express ; 28(11): 17086-17101, 2020 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-32549518

RESUMEN

3D point reconstruction is a crucial component in optical inspection. A direct reconstruction process is proposed by combining two similarity invariants in active vision. A planar reference with an isosceles-right-angle pattern and a coplanar laser are adopted to generate the laser projective point on the measured object. The first invariant is the image of the conic dual to the circular points (ICDCP), which is derived from the lines in two pairs of perpendicular directions on the reference pattern. The invariant provides the transform from the projection space to the similarity space. Then, the ratio of the line segments consisting of the laser projection points and reference points is constructed as the other similarity invariant, by which the laser projection point in the similarity space is converted to Euclidean space. The solution of the laser point is modeled by the ratio invariant of the line segments and improved by a special point selection to avoid nonlinear equations. Finally, the benchmark-camera distance, the benchmark-generator distance, the benchmark length, image noise, and the number of orthogonal lines are experimentally investigated to explore the effectiveness and reconstruction error of the method. The reconstruction error averages of 0.94, 1.22, 1.77, and 2.15 mm are observed from the experiment results with the benchmark-camera distances from 600 mm to 750 mm with a 50 mm interval. This proves the validity and practicability of the reconstruction method.

11.
Am J Physiol Heart Circ Physiol ; 317(6): H1221-H1230, 2019 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-31625780

RESUMEN

Dilated cardiomyopathy (DCM) is the most common cause of heart failure (HF) in children, resulting in high mortality and need for heart transplantation. The pathophysiology underlying pediatric DCM is largely unclear; however, there is emerging evidence that molecular adaptations and response to conventional HF medications differ between children and adults. To gain insight into alterations leading to systolic dysfunction in pediatric DCM, we measured cardiomyocyte contractile properties and sarcomeric protein phosphorylation in explanted pediatric DCM myocardium (N = 8 subjects) compared with nonfailing (NF) pediatric hearts (N = 8 subjects). Force-pCa curves were generated from skinned cardiomyocytes in the presence and absence of protein kinase A. Sarcomeric protein phosphorylation was quantified with Pro-Q Diamond staining after gel electrophoresis. Pediatric DCM cardiomyocytes demonstrate increased calcium sensitivity (pCa50 =5.70 ± 0.0291), with an associated decrease in troponin (Tn)I phosphorylation compared with NF pediatric cardiomyocytes (pCa50 =5.59 ± 0.0271, P = 0.0073). Myosin binding protein C and TnT phosphorylation are also lower in pediatric DCM, whereas desmin phosphorylation is increased. Pediatric DCM cardiomyocytes generate peak tension comparable to that of NF pediatric cardiomyocytes [DCM 29.7 mN/mm2, interquartile range (IQR) 21.5-49.2 vs. NF 32.8 mN/mm2, IQR 21.5-49.2 mN/mm2; P = 0.6125]. In addition, cooperativity is decreased in pediatric DCM compared with pediatric NF (Hill coefficient: DCM 1.56, IQR 1.31-1.94 vs. NF 1.94, IQR 1.36-2.86; P = 0.0425). Alterations in sarcomeric phosphorylation and cardiomyocyte contractile properties may represent an impaired compensatory response, contributing to the detrimental DCM phenotype in children.NEW & NOTEWORTHY Our study is the first to demonstrate that cardiomyocytes from infants and young children with dilated cardiomyopathy (DCM) exhibit increased calcium sensitivity (likely mediated by decreased troponin I phosphorylation) compared with nonfailing pediatric cardiomyocytes. Compared with published values in adult cardiomyocytes, pediatric cardiomyocytes have notably decreased cooperativity, with a further reduction in the setting of DCM. Distinct adaptations in cardiomyocyte contractile properties may contribute to a differential response to pharmacological therapies in the pediatric DCM population.


Asunto(s)
Calcio/metabolismo , Cardiomiopatía Dilatada/metabolismo , Miocitos Cardíacos/metabolismo , Troponina I/metabolismo , Calcio/farmacología , Proteínas Portadoras/metabolismo , Células Cultivadas , Niño , Preescolar , Humanos , Masculino , Contracción Miocárdica , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/fisiología , Fosforilación
12.
J Autoimmun ; 103: 102282, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31171475

RESUMEN

For quite a long time, the 11S proteasome activator REGɑ and REGß, but not REGγ, are known to control immunoproteasome and promote antigen processing. Here, we demonstrate that REGγ functions as an inhibitor for immunoproteasome and autoimmune disease. Depletion of REGγ promotes MHC class I-restricted presentation to prime CD8+ T cells in vitro and in vivo. Mice deficient for REGγ have elevation of CD8+ T cells and DCs, and develop age-related spontaneous autoimmune symptoms. Mechanistically, REGγ specifically interacts with phosphorylated STAT3 and promotes its degradation in vitro and in cells. Inhibition of STAT3 dramatically attenuates levels of LMP2/LMP7 and antigen presentation in cells lacking REGγ. Importantly, treatment with STAT3 or LMP2/7 inhibitor prevented accumulation of immune complex in REGγ-/- kidney. Moreover, REGγ-/- mice also expedites Pristane-induced lupus. Bioinformatics and immunohistological analyses of clinical samples have correlated lower expression of REGγ with enhanced expression of phosphorylated STAT3, LMP2 and LMP7 in human Lupus Nephritis. Collectively, our results support the concept that REGγ is a new regulator of immunoproteasome to balance autoimmunity.


Asunto(s)
Envejecimiento/inmunología , Autoantígenos/metabolismo , Enfermedades Autoinmunes/inmunología , Linfocitos T CD8-positivos/inmunología , Células Dendríticas/inmunología , Complejo de la Endopetidasa Proteasomal/metabolismo , Inhibidores de Proteasoma/metabolismo , Envejecimiento/genética , Animales , Presentación de Antígeno , Autoantígenos/genética , Enfermedades Autoinmunes/genética , Células Cultivadas , Cisteína Endopeptidasas/metabolismo , Antígenos de Histocompatibilidad Clase I/metabolismo , Ratones , Ratones Noqueados , Complejo de la Endopetidasa Proteasomal/genética , Factor de Transcripción STAT3/metabolismo
13.
Opt Express ; 27(26): 38567-38578, 2019 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-31878621

RESUMEN

The active-vision-based reconstruction is an advanced approach to characterize the spatial object. In the active vision, the planar laser is a kind of the moderate structured light for the robustness and adaptivity in the complicated illumination environment. However, as the planar laser is determined by 3 unknown degrees of freedom, the laser sensor should be calibrated in the immovable coordinate frame of reference (CFR), or be pre-calibrated in the coordinate frame of the camera (CFC) and moved with CFC. In the study, as the main improvement, the laser plane is attached to the simple 2D reference without strict constraints of the relative installation position and posture. The laser plane is desired to be flexibly moved and registered in CFC. The calibration is modeled by the closed loop of the camera, the cylindrical object, the planar laser and the 2D reference, in which the camera is twice considered as the bridge between the cylindrical object and the 2D reference. The calibration contributes the planar laser that is determined as a constant vector in CFR. Furthermore, the reconstruction is performed by the calibrated laser plane and refined by the optimization method. The method errors of 1.263, 1.517, 1.633, and 1.803 mm are evaluated by the experiments, which indicate the flexibility of the method and applicable prospects in the spatial reconstruction field.

14.
Appl Opt ; 58(29): 8092-8100, 2019 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-31674368

RESUMEN

Laser-plane-based vision reconstruction is an important approach for 3D profile measurement and optical inspection. This study develops a 3D reconstruction method to measure the object with a flexible method. The active vision reconstruction includes an external camera and a 3D reference with an internal camera and laser projector. The 3D calibration object, the external camera, and the 3D reference constitute a closed loop. The internal camera, the 3D calibration object, and the 3D reference compose the other closed loop. The intrinsic invariants of the 3D reference with an internal camera and laser projector are determined by the two loops above. The benefit of the method is to cancel the position constraint for the active vision system with the cubic LED reference and the monocular external camera. Furthermore, as the external camera captures only the images of the 3D reference, the reconstruction system of the projector and the camera is flexible to observe the occlusion location on the measured object. The methods, including the calibration model and reconstruction model of the measurement system, are verified by experiments to demonstrate the potential applications.

15.
J Pathol ; 241(4): 448-462, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27801498

RESUMEN

Oesophageal squamous cell carcinoma (ESCC), a leading lethal malignancy of the digestive tract, is characterized by marked gender disparity. Clarifying the roles of the function and regulatory pathway of the androgen receptor (AR) will improve our understanding of oesophageal cancer progression, thereby facilitating the personalized management of ESCC. Here we report evidence to show that AR is a key mediator of inflammatory signals in ESCC cancer progression. High AR expression was associated with poor overall survival in tobacco-using ESCC patients but not in ESCC patients not using tobacco. A gain and loss of AR function enhanced and repressed ESCC cell growth, respectively, by altering cell cycle progression. In mice bearing human ESCC xenografts, silencing AR expression attenuated tumour growth, whereas AR overexpression promoted tumour growth in mice of different androgen statuses (male, female, and castrated male). Array assays revealed that the inflammatory cytokine interleukin-6 (IL6) is a prominent AR target gene in ESCC. By directly binding to the IL6 promoter, AR enhances IL6 transcription, and IL6 can in turn activate AR expression, thus forming a reciprocal regulatory circuit to sustain STAT3 oncogenic signalling in ESCC. Moreover, high expression levels of both AR and IL6 in human ESCC predict poor clinical outcome in tobacco users. Together, these data establish that AR promotes ESCC growth and is associated with poor patient prognosis. The discovery of a positive feedback loop between IL6 and AR bridges the knowledge gaps among lifestyle factor-associated inflammation, gender disparity, and oesophageal carcinoma. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/patología , Regulación Neoplásica de la Expresión Génica , Receptores Androgénicos/genética , Receptores de Interleucina-6/genética , Transducción de Señal , Animales , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Línea Celular Tumoral , Proliferación Celular , Estudios de Cohortes , Progresión de la Enfermedad , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago , Femenino , Xenoinjertos , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Ratones , Ratones Desnudos , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Androgénicos/metabolismo , Receptores de Interleucina-6/metabolismo , Análisis de Supervivencia , Nicotiana/efectos adversos
16.
Cell Physiol Biochem ; 41(1): 227-238, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28214845

RESUMEN

BACKGROUND/AIMS: Microgravity leads to hydrodynamic alterations in the cardiovascular system and is associated with increased angiogenesis, an important aspect of endothelial cell behavior to initiate new vessel growth. Given the critical role of Rho GTPase-dependent cytoskeleton rearrangement in cell migration, small GTPase RhoA might play a potential role in microgravity-induced angiogenesis. METHODS: We examined the organization of actin filaments by FITC-conjugated phalloidin staining, as well as the expression and activity of RhoA by quantitative PCR and Western blot, in human umbilical vein endothelial cells (HUVECs) under normal gravity and simulated microgravity. Effect of simulated microgravity on the wound closure and tube formation in HUVECs, and their dependence on RhoA, were also analyzed by cell migration and tube formation assays. RESULTS: We show that in HUVECs actin filaments are disorganized and RhoA activity is reduced by simulated microgravity. Blocking RhoA activity either by C3 transferase Rho inhibitor or siRNA knockdown mimicked the effect of simulated microgravity on inducing actin filament disassembly, followed by enhanced wound closure and tube formation in HUVECs, which closely resembled effects seen on microgravity-treated cells. In contrast, overexpressing RhoA in microgravity-treated HUVECs restored the actin filaments, and decreased wound closure and tube formation abilities. CONCLUSION: These results suggest that RhoA inactivation is involved in the actin rearrangement-associated angiogenic responses in HUVECs during simulated microgravity.


Asunto(s)
Citoesqueleto de Actina/fisiología , Actinas/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Neovascularización Fisiológica/fisiología , Proteína de Unión al GTP rhoA/metabolismo , Movimiento Celular , Células Endoteliales de la Vena Umbilical Humana/citología , Humanos , Microscopía Fluorescente , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Simulación de Ingravidez , Proteína de Unión al GTP rhoA/antagonistas & inhibidores , Proteína de Unión al GTP rhoA/genética
17.
Opt Express ; 25(24): 29746-29760, 2017 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-29221011

RESUMEN

A flexible reconstruction method, which is based on the line re-projection errors of the laser plane, is presented for the profile recovery. The bi-cuboid references are designed to cover the large view-field of the camera. The local intrinsic and extrinsic parameter matrices of the camera are initially contributed by the RQ decomposition. Then the balance model is demonstrated to obtain the global parameter matrices in view of the refined projection in the camera coordinate system. The flexible laser plane is solved by the Plücker matrices of the projection laser lines that are generated from the homographies of the cubical references and the global parameter matrices. Furthermore, the laser plane and global parameter matrices are improved by the cost function that is constructed by the re-projection errors of the parameterized laser lines on the references. The reconstruction experiments are performed to verify the validity and the accuracy of the optimization method and the initial method. The impact factors of the measurement distance, the reference distance and the test distance are investigated in the experiments. The average reconstruction errors are 1.14 mm, 1.13 mm, 1.15 mm and 1.17 mm in the four groups of experiments, which shows the good application prospect of the profile reconstructions.

18.
J Biol Chem ; 290(18): 11729-40, 2015 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-25767119

RESUMEN

Specific p53 mutations abrogate tumor-suppressive functions by gaining new abilities to promote tumorigenesis. Inactivation of p53 is known to distort TGF-ß signaling, which paradoxically displays both tumor-suppressive and pro-oncogenic functions. The molecular mechanisms of how mutant p53 simultaneously antagonizes the tumor-suppressive and synergizes the tumor-promoting function of the TGF-ß pathway remain elusive. Here we demonstrate that mutant p53 differentially regulates subsets of TGF-ß target genes by enhanced binding to the MH2 domain in Smad3 upon the integration of ERK signaling, therefore disrupting Smad3/Smad4 complex formation. Silencing Smad2, inhibition of ERK, or introducing a phosphorylation-defective mutation at Ser-392 in p53 abrogates the R175H mutant p53-dependent regulation of these TGF-ß target genes. Our study shows a mechanism to reconcile the seemingly contradictory observations that mutant p53 can both attenuate and cooperate with the TGF-ß pathway to promote cancer cell malignancy in the same cell type.


Asunto(s)
Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Mutación , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/patología , Ratones , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Factores de Transcripción de la Familia Snail , Factores de Transcripción/metabolismo , Transcripción Genética
19.
Appl Opt ; 55(10): 2653-6, 2016 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-27139669

RESUMEN

A calibration method adopting Plücker matrices is proposed to explore the laser plane in a structured light measurement. The calibration model establishes the geometrical relationship among the camera, 2D target, and laser plane. The laser plane is constructed by multiple Plücker matrices of the dual 3D crossing lines between the laser plane and target planes in the camera coordinate system. Moreover, the validity of this calibration method is experimentally analyzed through the impact factors of noise magnitude and number of images. The mean errors of three directional angles of the normal vector to the laser plane are -0.174°, 0.170°, and -0.022°, respectively. The variances of the errors of three directional angles are 0.069°, 0.046°, and 0.160°, respectively. The maximal absolute errors of three directional angles are 1.362°, 1.351°, and 1.347°, respectively. The experiments prove that the calibration method is available to provide an accurate calibration for the laser plane.

20.
Proc Natl Acad Sci U S A ; 110(16): 6536-41, 2013 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-23550157

RESUMEN

The cytoplasmic RNA-induced silencing complex (RISC) contains dsRNA binding proteins, including protein kinase RNA activator (PACT), transactivation response RNA binding protein (TRBP), and Dicer, that process pre-microRNAs into mature microRNAs (miRNAs) that target specific mRNA species for regulation. There is increasing evidence for important functional interactions between the miRNA and nuclear receptor (NR) signaling networks, with recent data showing that estrogen, acting through the estrogen receptor, can modulate initial aspects of nuclear miRNA processing. Here, we show that the cytoplasmic RISC proteins PACT, TRBP, and Dicer are steroid receptor RNA activator (SRA) binding NR coregulators that target steroid-responsive promoters and regulate NR activity and downstream gene expression. Furthermore, each of the RISC proteins, together with Argonaute 2, associates with SRA and specific pre-microRNAs in both the nucleus and cytoplasm, providing evidence for links between NR-mediated transcription and some of the factors involved in miRNA processing.


Asunto(s)
Proteínas Portadoras/metabolismo , ARN Helicasas DEAD-box/metabolismo , Regulación de la Expresión Génica/genética , MicroARNs/metabolismo , Proteínas de Unión al ARN/metabolismo , Complejo Silenciador Inducido por ARN/metabolismo , Ribonucleasa III/metabolismo , Western Blotting , Fraccionamiento Celular , Inmunoprecipitación de Cromatina , Clonación Molecular , Células HEK293 , Células HeLa , Humanos , Luciferasas , Células MCF-7 , Plásmidos/genética , Interferencia de ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transfección , Técnicas del Sistema de Dos Híbridos
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