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1.
Acta Psychiatr Scand ; 149(2): 133-146, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38057974

RESUMO

BACKGROUND: Neuroticism is a psychological personality trait that has a significant impact on public health and is also a potential predisposing factor for adverse disease outcomes; however, comprehensive studies of the subsequently developed conditions are lacking. The starting point of disease trajectory in terms of genetic variation remains unclear. METHOD: Our study included 344,609 adult participants from the UK Biobank cohort who were virtually followed up from January 1, 1997. Neuroticism levels were assessed using 12 items from the Eysenck Personality Questionnaire. We performed a phenome-wide association analysis of neuroticism and subsequent diseases. Binomial tests and logistic regression models were used to test the temporal directionality and association between disease pairs to construct disease trajectories. We also investigated the association between polygenic risk scores (PRSs) for five psychiatric traits and high neuroticism. RESULTS: The risk for 59 diseases was significantly associated with high neuroticism. Depression, anxiety, irritable bowel syndrome, migraine, spondylosis, and sleep disorders were the most likely to develop, with hazard ratios of 6.13, 3.66, 2.28, 1.74, 1.74, and 1.71, respectively. The disease trajectory network revealed two major disease clusters: cardiometabolic and chronic inflammatory diseases. Medium/high genetic risk groups stratified by the PRSs of four psychiatric traits were associated with an elevated risk of high neuroticism. We further identified eight complete phenotypic trajectory clusters of medium or high genetic risk for psychotic, anxiety-, depression-, and stress-related disorders. CONCLUSION: Neuroticism plays an important role in the development of somatic and mental disorders. The full picture of disease trajectories from the genetic risk of psychiatric traits and neuroticism in early life to a series of diseases later provides evidence for future research to explore the etiological mechanisms and precision management.


Assuntos
Transtornos Mentais , Adulto , Humanos , Neuroticismo , Estudos Prospectivos , Transtornos Mentais/epidemiologia , Transtornos Mentais/genética , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/genética , Transtornos de Ansiedade/psicologia , Ansiedade
2.
Magn Reson Med ; 90(2): 569-582, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37125662

RESUMO

PURPOSE: Conventional 3D Look-Locker inversion recovery (LLIR) T1 mapping requires multi-repetition data acquisition to reconstruct images at different inversion times for T1 fitting. To ensure B1 robustness, sufficient time of delay (TD) is needed between repetitions, which prolongs scan time. This work proposes a novel deep learning-assisted LLIR MRI approach for rapid 3D T1 mapping without TD. THEORY AND METHODS: The proposed approach is based on the fact that T 1 * $$ {\mathrm{T}}_1^{\ast } $$ , the effective T1 in LLIR imaging, is independent of TD and can be estimated from both LLIR imaging with and without TD, while accurate conversion of T 1 * $$ {\mathrm{T}}_1^{\ast } $$ to T1 requires TD. Therefore, deep learning can be used to learn the conversion of T 1 * $$ {\mathrm{T}}_1^{\ast } $$ to T1 , which eliminates the need for TD. This idea was implemented for inversion-recovery-prepared Golden-angel RAdial Sparse Parallel T1 mapping (GraspT1 ). 39 GraspT1 datasets with a TD of 6 s (GraspT1 -TD6) were used for training, which also incorporates additional anatomical images. The trained network was applied for T1 estimation in 14 GraspT1 datasets without TD (GraspT1 -TD0). The robustness of the trained network was also tested. RESULTS: Deep learning-based T1 estimation from GraspT1 -TD0 is accurate compared to the reference. Incorporation of additional anatomical images improves the accuracy of T1 estimation. The technique is also robust against slight variation in spatial resolution, imaging orientation and scanner platform. CONCLUSION: Our approach eliminates the need for TD in 3D LLIR imaging without affecting the T1 estimation accuracy. It represents a novel use of deep learning towards more efficient and robust 3D LLIR T1 mapping.


Assuntos
Aprendizado Profundo , Imageamento por Ressonância Magnética/métodos , Imagens de Fantasmas , Reprodutibilidade dos Testes
3.
Eur Radiol ; 33(9): 6096-6106, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37410111

RESUMO

OBJECTIVE: To investigate the feasibility of using noninvasive neuroimaging methods in visualizing and evaluating the clearance of the glymphatic-meningeal lymphatic system (GMLS) in patients with arteriosclerotic cerebral small-vessel disease (CSVD) and controls. METHODS: This observational study recruited patients with high-burden CSVD and controls (age 50-80 years). At multiple time points before and after intravenous administration of a contrast agent, three-dimensional (3D) brain volume T1-weighted imaging and 3D Cube T2-fluid attenuated inversion recovery imaging were performed to visualize and assess the clearance of the glymphatics and meningeal lymphatic vessels (mLVs). We measured the signal intensity ratio (SIR) of four regions of interest representing the glymphatics and mLVs at each time point. The clearance rate at 24 h (CR24h) and changes in the SIR from baseline to 24 h (∆SIR) were defined as the clearance function. The analysis of variance was used to evaluate the group differences after adjusting for hypertension. RESULTS: A total of 20 CSVD patients and 15 controls were included. Cortical periarterial enhancement and the enhancement of enlarged perivascular spaces in the basal ganglia were respectively observed in 11 (55.00%) and 16 (80.00%) CSVD patients, but in none of controls. All CSVD patients and most of controls (80.00%) showed cortical perivenous enhancement. Para-sinus enhancement was observed in all participants. CSVD patients showed lower CR24h and higher ∆SIR of the glymphatics and mLVs (all p < 0.05). CONCLUSION: The impaired drainage of the GMLS in patients with high-burden CSVD could be visually evaluated using noninvasive neuroimaging methods with intravenous gadolinium-based contrast-enhancement. CLINICAL RELEVANCE STATEMENT: Dynamic intravenous contrast-enhanced MRI could visually evaluate the impaired drainage of the glymphatic-meningeal lymphatic system in patients with high-burden cerebral small-vessel disease and could help to explore a new therapeutic target. KEY POINTS: • Signal intensity changes in regions representing the glymphatic-meningeal lymphatic system (GMLS) can reflect the drainage function based on contrast-enhanced 3D-FLAIR and 3D T1-weighted MRI. • Impaired drainage of the GMLS in patients with high-burden CSVD can be visually evaluated using dynamic intravenous contrast-enhanced MRI. • This direct, noninvasive technique could serve as a basis for further GMLS studies and could help to explore a new therapeutic target in CSVD patients.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Sistema Glinfático , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Sistema Glinfático/diagnóstico por imagem , Gadolínio , Imageamento por Ressonância Magnética/métodos , Meninges , Administração Intravenosa
4.
Cell Mol Life Sci ; 79(5): 268, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35499593

RESUMO

FBXW2 is a poorly characterized F-box protein, as a tumor suppressor that inhibits growth and metastasis of lung cancer by promoting ubiquitylation and degradation of oncogenic proteins, including SKP2 and ß-catenin. However, what the biological functions of FBXW2 in prostate cancer cells and whether FBXW2 targets other substrates to involve in progression of prostate cancer is still unclear. Here, we reported that overexpression of FBXW2 attenuated proliferation and metastasis of PCa models both in vitro and in vivo, while FBXW2 depletion exhibited the opposite effects. Intriguingly, FBXW2 was an E3 ligase for EGFR in prostate cancer. EGFR protein level and its half-life were extended by FBXW2 depletion, while EGFR protein level was decreased, and its half-life was shortened upon overexpression of FBXW2, but not its dominant-negative mutant. Importantly, FBXW2 bond to EGFR via its consensus degron motif (TSNNST), and ubiquitylated and degraded EGFR, resulting in repression of EGF function. Thus, our data uncover a novel that FBXW2 as a tumor suppressor of prostate cancer, inhibits EGFR downstream by promoting EGFR ubiquitination and degradation, resulting in repression of cell proliferation and metastasis.


Assuntos
Proteínas F-Box , Neoplasias da Próstata , Linhagem Celular Tumoral , Proliferação de Células , Receptores ErbB/genética , Receptores ErbB/metabolismo , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Humanos , Masculino , Neoplasias da Próstata/patologia , Ubiquitinação
5.
World J Urol ; 40(2): 513-518, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34766214

RESUMO

OBJECTIVE: To compare the outcomes of mini percutaneous nephrolithotomy (mPNL) and retrograde intrarenal surgery (RIRS) for the management of 2-3 cm lower pole renal calculi (LPC) in obese patients. PATIENTS AND METHODS: 120 obese patients with 2-3 cm LPC were randomly divided into mPNL group and RIRS group. Demography, clinical characteristics, perioperative complications, and stone free rate (SFR) were recorded. Stone-free status means no stone on computed tomography 3 months after surgery, or residual fragments were less than 3 mm. RESULTS: Baseline characteristics were similar between the two groups. The mean stone burden was 585.39 ± 131.06 mm2 in the mPNL group and 548.64 ± 123.55 mm2 in the RIRS group (P = 0.125). The SFR of mPNL group was significantly better than that of RIRS group (86.2% vs 61.4%, P = 0.002). Besides, the overall complication rate was 22.4% in the mPNL group and 7% in the RIRS group (P = 0.02). Patients performed with mPNL required longer length of hospital stay than those with RIRS (P = 0.001). There were no significant differences in operative time and stone composition between the two groups. CONCLUSION: In our study, both mPNL and RIRS are safe and effective techniques for the treatment of 2-3 cm LPC in obese patients. Compared to RIRS, mPNL has better SFR at the expense of the higher incidence of complications and prolonged length of hospital stay.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Humanos , Cálculos Renais/complicações , Cálculos Renais/cirurgia , Tempo de Internação , Nefrolitotomia Percutânea/métodos , Nefrostomia Percutânea/métodos , Obesidade/complicações , Resultado do Tratamento
6.
Mol Cancer ; 20(1): 4, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397425

RESUMO

Circular RNAs (circRNAs), which are single-stranded closed-loop RNA molecules lacking terminal 5' caps and 3' poly(A) tails, are attracting increasing scientific attention for their crucial regulatory roles in the occurrence and development of various diseases. With the rapid development of high-throughput sequencing technologies, increasing numbers of differentially expressed circRNAs have been identified in bladder cancer (BCa) via exploration of the expression profiles of BCa and normal tissues and cell lines. CircRNAs are critically involved in BCa biological behaviours, including cell proliferation, tumour growth suppression, cell cycle arrest, apoptosis, invasion, migration, metastasis, angiogenesis, and cisplatin chemoresistance. Most of the studied circRNAs in BCa regulate cancer biological behaviours via miRNA sponging regulatory mechanisms. CircRNAs have been reported to be significantly associated with many clinicopathologic characteristics of BCa, including tumour size, grade, differentiation, and stage; lymph node metastasis; tumour numbers; distant metastasis; invasion; and recurrence. Moreover, circRNA expression levels can be used to predict BCa patients' survival parameters, such as overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). The abundance, conservation, stability, specificity and detectability of circRNAs render them potential diagnostic and prognostic biomarkers for BCa. Additionally, circRNAs play crucial regulatory roles upstream of various signalling pathways related to BCa carcinogenesis and progression, reflecting their potential as therapeutic targets for BCa. Herein, we briefly summarize the expression profiles, biological functions and mechanisms of circRNAs and the potential clinical applications of these molecules for BCa diagnosis, prognosis, and targeted therapy.


Assuntos
Perfilação da Expressão Gênica , RNA Circular/genética , Neoplasias da Bexiga Urinária/genética , Apoptose/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Prognóstico , RNA Circular/biossíntese , RNA Circular/metabolismo , Neoplasias da Bexiga Urinária/patologia
7.
NMR Biomed ; 34(7): e4531, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33902155

RESUMO

In this work, we propose a free-breathing magnetic resonance fingerprinting (MRF) method that can be used to obtain B1+ -robust quantitative T1 maps of the abdomen in a clinically acceptable time. A three-dimensional MRF sequence with a radial stack-of-stars trajectory was implemented, and its k-space acquisition ordering was adjusted to improve motion-robustness in the context of MRF. The flip angle pattern was optimized using the Cramér-Rao Lower Bound, and the encoding efficiency of sequences with 300, 600, 900 and 1800 flip angles was evaluated. To validate the sequence, a movable multicompartment phantom was developed. Reference multiparametric maps were acquired under stationary conditions using a previously validated MRF method. Periodic motion of the phantom was used to investigate the motion-robustness of the proposed sequence. The best performing sequence length (600 flip angles) was used to image the abdomen during a free-breathing volunteer scan. When using a series of 600 or more flip angles, the estimated T1 values in the stationary phantom showed good agreement with the reference scan. Phantom experiments revealed that motion-related artifacts can appear in the quantitative maps and confirmed that a motion-robust k-space ordering is essential. The in vivo scan demonstrated that the proposed sequence can produce clean parameter maps while the subject breathes freely. Using this sequence, it is possible to generate B1+ -robust quantitative maps of T1 and B1+ next to M0 -weighted images under free-breathing conditions at a clinically usable resolution within 5 min.


Assuntos
Abdome/diagnóstico por imagem , Imageamento por Ressonância Magnética , Respiração , Humanos , Movimento (Física) , Imagens de Fantasmas
8.
Eur Radiol ; 31(9): 6736-6746, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33638020

RESUMO

OBJECTIVE: To compare the safety, effectiveness, and feasibility of contrast-enhanced ultrasound (CEUS) versus conventional ultrasound-guided percutaneous nephrolithotomy (PCNL) in patients with nondilated collecting system. METHODS: Between July 2018 and July 2020, 160 kidney stone patients with nondilated collecting system planned for PCNL were randomly assigned into two groups, CEUS with retrograde ureteral contrast injection and conventional ultrasound with retrograde ureteral normal saline injection. Patient's demographics, the success rate of puncture, success rate of a single-needle puncture, number of punctures, puncture time, perioperative outcomes, stone-free rate, and incidence of complications were compared. RESULTS: The success rate of a single-needle puncture for CEUS-guided PCNL was higher than that in the conventional ultrasound group (88.5% vs. 73.7%, p = 0.02). Patients performed with CEUS-guided PCNL required less needle passes (p = 0.02), shorter needle puncture time (p = 0.031), and shorter channel establishment time (p = 0.04) than those guided with conventional ultrasound. The postoperative hemoglobin decrease in the CEUS-guided PCNL group was less than that of the control group (p = 0.02). There was no significant difference in operating time, length of hospital stays, kidney function change, and complications between the two groups (p > 0.05). The 1-month stone-free rate was 94.9% in the CEUS group and 90.8% in the control group (p > 0.05). CONCLUSIONS: Compared with conventional ultrasound, CEUS-guided PCNL may facilitate ultrasound-guided PCNL for patients without hydronephrosis, and benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800016981 KEY POINTS: • Compared with conventional ultrasound, CEUS-guided PCNL is a safe and efficacious procedure for kidney stone patients with nondilated collecting system. • Compared with conventional ultrasound, CEUS-guided PCNL benefited with a higher success rate of a single-needle puncture, less needle passes, shorter puncture time, and lower postoperative Hb drop. • CEUS-guided PCNL associated with the more accurate needle puncture and acceptable complications.


Assuntos
Cálculos Renais , Nefrolitotomia Percutânea , Nefrostomia Percutânea , Humanos , Cálculos Renais/diagnóstico por imagem , Cálculos Renais/cirurgia , Resultado do Tratamento , Ultrassonografia , Ultrassonografia de Intervenção
9.
Sensors (Basel) ; 21(24)2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34960445

RESUMO

With the widespread application of machine learning methods, the continuous improvement of forecast accuracy has become an important task, which is especially crucial for landslide displacement predictions. This study aimed to propose a novel prediction model to improve accuracy in landslide prediction, based on the combination of multiple new algorithms. The proposed new method includes three parts: data preparation, multi-swarm intelligence (MSI) optimization, and displacement prediction. In the data preparation, the complete ensemble empirical mode decomposition (CEEMD) is adopted to separate the trend and periodic displacements from the observed cumulative landslide displacement. The frequency component and residual component of reconstructed inducing factors that related to landslide movements are also extracted by the CEEMD and t-test, and then picked out with edit distance on real sequence (EDR) as input variables for the support vector regression (SVR) model. MSI optimization algorithms are used to optimize the SVR model in the MSI optimization; thus, six predictions models can be obtained that can be used in the displacement prediction part. Finally, the trend and periodic displacements are predicted by six optimized SVR models, respectively. The trend displacement and periodic displacement with the highest prediction accuracy are added and regarded as the final prediction result. The case study of the Shiliushubao landslide shows that the prediction results match the observed data well with an improvement in the aspect of average relative error, which indicates that the proposed model can predict landslide displacements with high precision, even when the displacements are characterized by stepped curves that under the influence of multiple time-varying factors.

10.
Magn Reson Med ; 84(1): 128-141, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31762101

RESUMO

PURPOSE: To study the effects of magnetization transfer (MT, in which a semi-solid spin pool interacts with the free pool), in the context of magnetic resonance fingerprinting (MRF). METHODS: Simulations and phantom experiments were performed to study the impact of MT on the MRF signal and its potential influence on T1 and T2 estimation. Subsequently, an MRF sequence implementing off-resonance MT pulses and a dictionary with an MT dimension, generated by incorporating a two-pool model, were used to estimate the fractional pool size in addition to the B1+ , T1 , and T2 values. The proposed method was evaluated in the human brain. RESULTS: Simulations and phantom experiments showed that an MRF signal obtained from a cross-linked bovine serum sample is influenced by MT. Using a dictionary based on an MT model, a better match between simulations and acquired MR signals can be obtained (NRMSE 1.3% vs. 4.7%). Adding off-resonance MT pulses can improve the differentiation of MT from T1 and T2 . In vivo results showed that MT affects the MRF signals from white matter (fractional pool-size ~16%) and gray matter (fractional pool-size ~10%). Furthermore, longer T1 (~1060 ms vs. ~860 ms) and T2 values (~47 ms vs. ~35 ms) can be observed in white matter if MT is accounted for. CONCLUSION: Our experiments demonstrated a potential influence of MT on the quantification of T1 and T2 with MRF. A model that encompasses MT effects can improve the accuracy of estimated relaxation parameters and allows quantification of the fractional pool size.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Animais , Encéfalo/diagnóstico por imagem , Bovinos , Humanos , Espectroscopia de Ressonância Magnética , Imagens de Fantasmas , Reprodutibilidade dos Testes
11.
Sensors (Basel) ; 20(17)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32867248

RESUMO

Cyclic wetting and drying processes have been considered as important factors that accelerate the weathering process and have deteriorative effects on rock properties. In the present study, a fully nondestructive and noninvasive testing approach utilizing micro-CT and ultrasonic wave velocity tests was employed to investigate the microstructure of slate under wetting and drying cycles. We studied variations in the physical properties, including the dry weight and the velocities of P- and S-waves versus the number of wetting and drying cycles. The internal microstructural distributions were visualized and quantified by the 3D reconstruction and hybrid image segmentation of CT images. The degree of deterioration caused by wetting and drying cycles was reflected by exponential decreases of physical properties, including dry weight and velocities of the P- and S-waves. Parameters relating to the microfracture diameter, volume, etc. were quantified. The nondestructive and noninvasive testing approach utilizing micro-CT and ultrasonic wave velocity tests has potential for the detection and visualization of the internal microstructure of rock under wetting and drying cycles.

12.
Sensors (Basel) ; 20(15)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32752029

RESUMO

Accurately predicting the surface displacement of the landslide is important and necessary. However, most of the existing research has ignored the frequency component of inducing factors and how it affects the landslide deformation. Therefore, a hybrid displacement prediction model based on time series theory and various intelligent algorithms was proposed in this paper to study the effect of frequency components. Firstly, the monitoring displacement of landslide from the Three Gorges Reservoir area (TGRA) was decomposed into the trend and periodic components by complete ensemble empirical mode decomposition (CEEMD). The trend component can be predicted by the least square method. Then, time series of inducing factors like rainfall and reservoir level was reconstructed into high frequency components and low frequency components with CEEMD and t-test, respectively. The dominant factors were selected by the method of dynamic time warping (DTW) from the frequency components and other common factors (e.g., current monthly rainfall). Finally, the ant colony optimization-based support vector machine regression (ACO-SVR) is utilized for prediction purposes in the TGRA. The results demonstrate that after considering the frequency components of landslide-induced factors, the accuracy of the displacement prediction model based on ACO-SVR is better than that of other models based on SVR and GA-SVR.

13.
J Cell Physiol ; 234(12): 22635-22647, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31102300

RESUMO

Calcium-activated nucleotidase 1 (CANT1, belongs to the apyrase family, is widely expressed in various organs. However, the biological function of CANT1 remains poorly explored. In this study, we aimed to investigate the expression profile and functions of CANT1 in clear cell renal cell carcinoma (ccRCC). Our data show that the protein level of CANT1 was significantly higher in tumor tissues than in adjacent normal tissues. CANT1 silencing suppressed cell proliferation, migration, and invasion obviously in 769-P and 786-O cells, arrested cell cycle in S phase and promoted apoptosis in 769-P cells. In conclusion, the present study shows the different expression mode of CANT1 in human ccRCC tumor tissue and adjacent normal tissue, denotes the function of CANT1 in ccRCC cells and provides potential molecular mechanisms and pathways of CANT1 antitumor function in ccRCC.


Assuntos
Carcinoma de Células Renais/enzimologia , Proliferação de Células , Neoplasias Renais/enzimologia , Nucleotidases/metabolismo , Interferência de RNA , Apoptose , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular , Repressão Enzimática , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Invasividade Neoplásica , Nucleotidases/genética , Pontos de Checagem da Fase S do Ciclo Celular , Transdução de Sinais
14.
Cell Physiol Biochem ; 50(1): 261-276, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30282072

RESUMO

BACKGROUND/AIMS: Treatment options for metastatic castrate-resistant prostate cancer (mCRPC) are limited and typically centered on paclitaxel-based chemotherapy. In this study, we aimed to evaluate whether miR-34a attenuates chemoresistance to paclitaxel by regulating target genes associated with drug resistance. METHODS: We used data from The Cancer Genome Atlas to compare miR-34a expression levels in prostate cancer (PC) tissues with normal prostate tissues. The effects of miR-34a inhibition and overexpression on PC proliferation were evaluated in vitro via Cell Counting Kit-8 (CCK-8) proliferation, colony formation, apoptosis, and cell-cycle assays. A luciferase reporter assay was employed to identify the interactions between miR-34a and specific target genes. To determine the effects of up-regulation of miR-34a on tumor growth and chemo-resistance in vivo, we injected PC cells overexpressing miR-34a into nude mice subcutaneously and evaluated the rate of tumor growth during paclitaxel treatment. We examined changes in the expression levels of miR-34a target genes JAG1 and Notch1 and their downstream genes via miR-34a transfection by quantitative reverse transcription PCR (qRT-PCR) and western blot assay. RESULTS: miR-34a served as an independent predictor of reduced patient survival. MiR-34a was down-regulated in PC-3PR cells compared with PC-3 cells. The CCK-8 assay showed that miR-34a overexpression resulted in increased sensitivity to paclitaxel while miR-34a down-regulation resulted in chemoresistance to paclitaxel in vitro. A study of gain and loss in a series of functional assays revealed that PC cells expressing miR-34a were chemosensitive. Furthermore, the overexpression of miR-34a increased the sensitivity of PC-3PR cells to chemotherapy in vivo. The luciferase reporter assay confirmed that JAG1 and Notch1 were directly targeted by miR-34a. Interestingly, western blot analysis and qRT-PCR confirmed that miR-34a inhibited the Notch1 signaling pathway. We found that miR-34a increased the chemosensitivity of PC-3PR cells by directly repressing the TCF1/ LEF1 axis. CONCLUSION: Our results showed that miR-34a is involved in the development of chemosensitivity to paclitaxel. By regulating the JAG1/Notch1 axis, miR-34a or its target genes JAG1 or Notch1 might serve as potential predictive biomarkers of response to paclitaxel-based chemotherapy and/or therapeutic targets that will help to overcome chemoresistance at the mCRPC stage.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Proteína Jagged-1/metabolismo , MicroRNAs/metabolismo , Paclitaxel/farmacologia , Neoplasias da Próstata/patologia , Receptor Notch1/metabolismo , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Antagomirs/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Humanos , Proteína Jagged-1/genética , Estimativa de Kaplan-Meier , Masculino , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Paclitaxel/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade , Receptor Notch1/genética , Transdução de Sinais/efeitos dos fármacos
15.
Magn Reson Med ; 80(2): 641-647, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29266468

RESUMO

PURPOSE: To demonstrate the feasibility of the so-called quadrupolar jump-and-return (QJR) pulse sequence by assessing its performance on the contrast modification to knee cartilage and quality of fluid suppression in the knee joint in vivo at 7T. METHODS: The right knee joints of five healthy volunteers (3 males: mean age = 32.4 ± 1.3 years; 2 females: mean age = 27.9 ± 1.0 years; mean age = 30.6 ± 2.7 years) were scanned on a 7T scanner with variation of the delay in the QJR sequence from 1 ms to 5 ms. For one healthy volunteer, the QJR scan with the delay of 3 ms and the inversion-recovery (IR) scan were performed. Numerical simulations were conducted to evaluate the effects of B0 - and B1 -field inhomogeneities and residual quadrupolar couplings on fluid suppression and tissue contrast, respectively. RESULTS: The QJR sequence suppressed the fluid signal from the artery and produced the contrast of knee cartilage in vivo. Its performance was comparable to that of the conventional IR sequence. Numerical simulations suggested that the fluid suppression may not be affected much by field inhomogeneities but that a distribution of residual quadrupolar couplings and weak RF pulses may interfere with the clear interpretation of cartilage contrast. CONCLUSION: This preliminary work demonstrated that the QJR pulse sequence produces contrast for knee cartilage while suppressing the fluid signal from the artery. The knee cartilage contrast and quality of fluid suppression obtained from the QJR sequence were comparable to those of the IR sequence. Magn Reson Med 80:641-647, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Assuntos
Articulação do Joelho/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Sódio/química , Adulto , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Articulação do Joelho/irrigação sanguínea , Articulação do Joelho/química , Masculino , Processamento de Sinais Assistido por Computador
16.
Eur Radiol ; 28(1): 133-142, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28687914

RESUMO

OBJECTIVES: To evaluate the potential of sodium MRI to detect changes over time of apparent sodium concentration (ASC) in articular cartilage in patients with knee osteoarthritis (OA). METHODS: The cartilage of 12 patients with knee OA were scanned twice over a period of approximately 16 months with two sodium MRI sequences at 7 T: without fluid suppression (radial 3D) and with fluid suppression by adiabatic inversion recovery (IR). Changes between baseline and follow-up of mean and standard deviation of ASC (in mM), and their rate of change (in mM/day), were measured in the patellar, femorotibial medial and lateral cartilage regions for each subject. A matched-pair Wilcoxon signed rank test was used to assess significance of the changes. RESULTS: Changes in mean and in standard deviation of ASC, and in their respective rate of change over time, were only statistically different when data was acquired with the fluid-suppressed sequence. A significant decrease (p = 0.001) of approximately 70 mM in mean ASC was measured between the two IR scans. CONCLUSION: Quantitative sodium MRI with fluid suppression by adiabatic IR at 7 T has the potential to detect a decrease of ASC over time in articular cartilage of patients with knee osteoarthritis. KEY POINTS: • Sodium MRI can detect apparent sodium concentration (ASC) in cartilage • Longitudinal study: sodium MRI can detect changes in ASC over time • Potential for follow-up studies of cartilage degradation in knee osteoarthritis.


Assuntos
Cartilagem Articular/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Osteoartrite do Joelho/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Reprodutibilidade dos Testes , Sódio
18.
NMR Biomed ; 30(10)2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28632901

RESUMO

The purpose of this study was to demonstrate the feasibility of biexponential T1ρ relaxation mapping of human knee cartilage in vivo. A three-dimensional, customized, turbo-flash sequence was used to acquire T1ρ -weighted images from healthy volunteers employing a standard 3-T MRI clinical scanner. A series of T1ρ -weighted images was fitted using monoexponential and biexponential models with two- and four-parametric non-linear approaches, respectively. Non-parametric Kruskal-Wallis and Mann-Whitney U-statistical tests were used to evaluate the regional relaxation and gender differences, respectively, with a level of significance of P = 0.05. Biexponential relaxations were detected in the cartilage of all volunteers. The short and long relaxation components of T1ρ were estimated to be 6.9 and 51.0 ms, respectively. Similarly, the fractions of short and long T1ρ were 37.6% and 62.4%, respectively. The monoexponential relaxation of T1ρ was 32.6 ms. The experiments showed good repeatability with a coefficient of variation (CV) of less than 20%. A biexponential relaxation model showed a better fit than a monoexponential model to the T1ρ relaxation decay in knee cartilage. Biexponential T1ρ components could potentially be used to increase the specificity to detect early osteoarthritis by the measurement of different water compartments and their fractions.


Assuntos
Cartilagem Articular/diagnóstico por imagem , Joelho/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Animais , Bovinos , Simulação por Computador , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Método de Monte Carlo , Reprodutibilidade dos Testes
19.
J Foot Ankle Surg ; 56(1): 26-29, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27989341

RESUMO

During the previous 2 decades, numerous surgical procedures have become available to treat osteochondral lesions of the talus. The objective of the present study was to use 7 Tesla (7T) magnetic resonance imaging (MRI) to quantify and compare T2 values (a marker of collagen architecture) of native tibiotalar cartilage and cartilage repair tissue in patients treated with a juvenile particulate allograft for osteochondral lesions of the talus. The institutional review board approved the present study, and all subjects provided written informed consent. We scanned the ankles of 7 cartilage repair patients using a 7T MRI scanner with a multi-echo spin-echo sequence to measure the cartilage T2 values. We assessed the cartilage T2 values in the talar repair tissue, adjacent native talar cartilage, and overlying tibial cartilage. We compared the differences between groups using the paired t test. The talar cartilage repair tissue demonstrated greater mean T2 relaxation times compared with the native adjacent talar cartilage (64.88 ± 12.23 ms versus 49.56 ± 7.82 ms; p = .043). The tibial cartilage regions overlying these talar cartilage regions demonstrated a trend toward greater T2 relaxation times (77.00 ± 31.29 ms versus 59.52 ± 7.89 ms; p = .067). 7T MRI can detect differences in T2 values in cartilage repair tissue compared with native cartilage and could be useful for monitoring the status of cartilage health after surgical intervention.


Assuntos
Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/cirurgia , Imagem Ecoplanar/métodos , Tálus/cirurgia , Transplante de Tecidos/métodos , Adulto , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Cartilagem Articular/patologia , Estudos de Viabilidade , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Osteocondrite/diagnóstico por imagem , Osteocondrite/cirurgia , Estudos Retrospectivos , Fatores de Risco , Estudos de Amostragem , Tálus/diagnóstico por imagem , Tálus/patologia , Transplante Homólogo/métodos , Resultado do Tratamento
20.
Magn Reson Med ; 74(1): 225-230, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25078605

RESUMO

PURPOSE: To assess the feasibility of mapping the kinetics and unidirectional fluxes of inorganic phosphate (Pi) to adenosine triphosphate (ATP) reactions in the entire volume of the lower leg muscles using a three-dimensional saturation transfer (ST) phosphorus (31 P) imaging sequence. THEORY AND METHODS: We imaged the lower leg muscles of five healthy subjects at 7.0 Tesla. The total experimental time was 45 min. We quantified muscle-specific forward reaction rate constants (k'f ) and metabolic fluxes (Vf ) of the Pi-to-ATP reaction in the tibialis anterior, the gastrocnemius, and the soleus. RESULTS: In the tibialis anterior, k'f and Vf were 0.11 s-1 ± 0.03 (mean ± standard deviation) and 0.34 mM s-1 ± 0.10, respectively. In the gastrocnemius, k'f was 0.11 s-1 ± 0.04 and Vf was 0.37 mM s-1 ± 0.11, while in the soleus muscle k'f was 0.10 s-1 ± 0.02 and Vf was 0.36 mM s-1 ± 0.14. CONCLUSION: Our results suggest that mapping the kinetics and unidirectional fluxes from Pi-to-ATP in both the anterior and posterior muscles of the lower leg is feasible at ultra-high field and may provide useful insights for the study of insulin resistance, diabetes and aging. Magn Reson Med 74:225-230, 2015. © 2014 Wiley Periodicals, Inc.

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