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1.
JCI Insight ; 6(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622800

RESUMO

The role and mechanisms for upregulating complement factor B (CFB) expression in podocyte dysfunction in diabetic kidney disease (DKD) are not fully understood. Here, analyzing Gene Expression Omnibus GSE30528 data, we identified genes enriched in mTORC1 signaling, CFB, and complement alternative pathways in podocytes from patients with DKD. In mouse models, podocyte mTOR complex 1 (mTORC1) signaling activation was induced, while blockade of mTORC1 signaling reduced CFB upregulation, alternative complement pathway activation, and podocyte injury in the glomeruli. Knocking down CFB remarkably alleviated alternative complement pathway activation and DKD in diabetic mice. In cultured podocytes, high glucose treatment activated mTORC1 signaling, stimulated STAT1 phosphorylation, and upregulated CFB expression, while blockade of mTORC1 or STAT1 signaling abolished high glucose-upregulated CFB expression. Additionally, high glucose levels downregulated protein phosphatase 2Acα (PP2Acα) expression, while PP2Acα deficiency enhanced high glucose-induced mTORC1/STAT1 activation, CFB induction, and podocyte injury. Taken together, these findings uncover a mechanism by which CFB mediates podocyte injury in DKD.

2.
Small ; : e2102016, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34608752

RESUMO

As a favorable candidate for the next-generation anode materials, metallic lithium is faced with two crucial problems: uncontrollable lithium plating/stripping process and huge volume expansion during cycling. Herein, a 3D lithiophilic skeleton modified with nanoscale Bi sheets (Ni@Bi Foam, i.e., NBF) through one-step facile substitution reaction is constructed. Benefiting from the nanoscale modification, smooth and dense lithiophilic Li3 Bi layer is in situ formed, which improves the uniform deposition of Li subsequently. Meanwhile, the 3D structure inhibits the growth of Li dendrites effectively by reducing local areal current density. Consequently, the NBF exhibits outstanding cycling stability with a high average Coulombic efficiency of 98.46% at 1 mA cm-2 with 1 mAh cm-2 (>500 cycles). Symmetrical cell with NBF exhibits a high reversibility at 1 mA cm-2 with 1 mAh cm-2 (>2000 h). Moreover, superior long-term cycling and rate performance of NBF@Li anode are also acquired when assembled with high areal loading of LiFePO4 (10.1 mg cm-2 ) cathode (Negative/Positive ratio: 2.91). Even in anode-free metal lithium batteries, NBF has higher capacity during cycling compared with NF. To conclude, NBF shows excellent electrochemical performance and provides an idea of facile preparation method which can be extend to other metal batteries.

3.
Biomed Eng Online ; 20(1): 101, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627279

RESUMO

BACKGROUND: Neural-network methods have been widely used for the prediction of dose distributions in radiotherapy. However, the prediction accuracy of existing methods may be degraded by the problem of dose imbalance. In this work, a new loss function is proposed to alleviate the dose imbalance and achieve more accurate prediction results. The U-Net architecture was employed to build a prediction model. Our study involved a total of 110 patients with left-breast cancer, who were previously treated by volumetric-modulated arc radiotherapy. The patient dataset was divided into training and test subsets of 100 and 10 cases, respectively. We proposed a novel 'sharp loss' function, and a parameter γ was used to adjust the loss properties. The mean square error (MSE) loss and the sharp loss with different γ values were tested and compared using the Wilcoxon signed-rank test. RESULTS: The sharp loss achieved superior dose prediction results compared to those of the MSE loss. The best performance with the MSE loss and the sharp loss was obtained when the parameter γ was set to 100. Specifically, the mean absolute difference values for the planning target volume were 318.87 ± 30.23 for the MSE loss versus 144.15 ± 16.27 for the sharp loss with γ = 100 (p < 0.05). The corresponding values for the ipsilateral lung, the heart, the contralateral lung, and the spinal cord were 278.99 ± 51.68 versus 198.75 ± 61.38 (p < 0.05), 216.99 ± 44.13 versus 144.86 ± 43.98 (p < 0.05), 125.96 ± 66.76 versus 111.86 ± 47.19 (p > 0.05), and 194.30 ± 14.51 versus 168.58 ± 25.97 (p < 0.05), respectively. CONCLUSIONS: The sharp loss function could significantly improve the accuracy of radiotherapy dose prediction.

5.
Int J Mol Med ; 48(5)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34498713

RESUMO

Investigating the factors that influence the inflammatory response of microglial cells is crucial for understanding the pathogenesis of cryptococcal meningitis (CM). MicroRNAs (miRNAs/miRs) play an important role in inducing host defenses and activating the immune response during microbial infection; however, the regulatory mechanisms of miRNAs in cryptococcal meningitis remain poorly defined. In a previous study, the authors assessed the miRNA profiles of THP­1 (human acute monocytic leukemia cells) cells following Cryptococcus neoformans (C. neoformans) infection. In the present study, it was found that miR­4792 expression was downregulated in BV2 cells infected with C. neoformans, whilst that of its target gene, epidermal growth factor receptor (EGFR), was upregulated. Infected cells in which miR­4792 was overexpressed exhibited a decreased EGFR transcript expression, reduced mitogen­activated protein kinase (MAPK) signaling and a decreased secretion of inflammatory cytokines. In addition, following antifungal treatment in patients with cryptococcal meningitis, the levels of miR­4792 in the cerebrospinal fluid significantly increased, whilst the expression of EGFR significantly decreased. In addition, receiver operator characteristic analysis revealed miR­4792 (AUCROC=0.75) and EGFR (AUCROC=0.79) as potential diagnostic markers in patients with cryptococcal meningitis.

6.
Sci Prog ; 104(3): 368504211038162, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34519556

RESUMO

Fully convolutional networks were developed for predicting optimal dose distributions for patients with left-sided breast cancer and compared the prediction accuracy between two-dimensional and three-dimensional networks. Sixty cases treated with volumetric modulated arc radiotherapy were analyzed. Among them, 50 cases were randomly chosen to conform the training set, and the remaining 10 were to construct the test set. Two U-Net fully convolutional networks predicted the dose distributions, with two-dimensional and three-dimensional convolution kernels, respectively. Computed tomography images, delineated regions of interest, or their combination were considered as input data. The accuracy of predicted results was evaluated against the clinical dose. Most types of input data retrieved a similar dose to the ground truth for organs at risk (p > 0.05). Overall, the two-dimensional model had higher performance than the three-dimensional model (p < 0.05). Moreover, the two-dimensional region of interest input provided the best prediction results regarding the planning target volume mean percentage difference (2.40 ± 0.18%), heart mean percentage difference (4.28 ± 2.02%), and the gamma index at 80% of the prescription dose are with tolerances of 3 mm and 3% (0.85 ± 0.03), whereas the two-dimensional combined input provided the best prediction regarding ipsilateral lung mean percentage difference (4.16 ± 1.48%), lung mean percentage difference (2.41 ± 0.95%), spinal cord mean percentage difference (0.67 ± 0.40%), and 80% Dice similarity coefficient (0.94 ± 0.01). Statistically, the two-dimensional combined inputs achieved higher prediction accuracy regarding 80% Dice similarity coefficient than the two-dimensional region of interest input (0.94 ± 0.01 vs 0.92 ± 0.01, p < 0.05). The two-dimensional data model retrieves higher performance than its three-dimensional counterpart for dose prediction, especially when using region of interest and combined inputs.

7.
Huan Jing Ke Xue ; 42(9): 4246-4256, 2021 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-34414722

RESUMO

Source identification and health risk assessment of heavy metals in groundwater is one of the key issues in China's new era of environmental management. In order to reveal the status, sources, and health risk of pollutants in groundwater of the Leizhou Peninsula, 44 groundwater samples were collected, and the concentrations and spatial distribution of Cr, Mn, Cu, Zn, As, Cd, Hg, and Pb were measured and analyzed. The sources of heavy metals in groundwater were then determined through correlation coefficient and principal component analysis. Finally, the health risk model was used to evaluate the different health risks associated with these heavy metals. The results showed that the average value of heavy metal elements in groundwater of the Leizhou Peninsula does not inferior to the class Ⅱ water quality standard(GB/T 14848-2017). However, As, Mn, and Cd do not meet the standard. The overall spatial distribution indicated obvious spatial differences, with higher values in the south than in the north. Heavy metal sources can be identified as three principal components (PCs). PC1 (Cu, Zn, Cd, and Pb) metals mainly originate from industrial, agricultural, and traffic sources. PC2 (Cr, Mn, and As) sources can be both natural and man-made, and PC3 (Hg) sources are primarily man-made. For the groundwater of the Leizhou Peninsula, the health risks of 8 metals are with the acceptable range, the carcinogenic risk of adults is higher than that of children, and the risk of drinking exposure is higher than that of skin exposure. The study shows that the environmental protection department should encourage the rational exploitation of groundwater resources and control the sources of pollution to reduce health risks.


Assuntos
Poluentes Ambientais , Água Subterrânea , Metais Pesados , Adulto , Criança , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Medição de Risco
8.
Front Biosci (Landmark Ed) ; 26(6): 125-134, 2021 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-34162041

RESUMO

This study aimed to investigate the effects of advanced glycation end products (AGEs) on the calcification of human arterial smooth muscle cells (HASMCs) and to explore whether AGEs can promote the calcification of HASMCs by activating the phosphoinositide 3-kinase (PI3K)/AKT-glycogen synthase kinase 3 beta (GSK3-ß) axis. Cultured HASMCs were divided into five groups: blank control group, dimethyl sulfoxide (vehicle) group, AGEs group, LY294002 (AKT inhibitor) group, and TWS119 (GSK3-ß inhibitor) group. Cells were pretreated with either vehicle, LY294002, or TWS119 for 2 hours followed by incubation with AGEs (25 µg/mL) for 5 days, and the expression levels of proteins in each group were analyzed by western blotting. AGE treatment promoted HASMC calcification, which coincided with increased expression of p-AKT and p-GSK3-ß (serine 9). Also, AGEs upregulated the expression of osteoprotegerin and bone morphogenetic protein, and these effects were suppressed by LY294002 but enhanced by TWS119. In conclusion, AGEs promote calcification of HASMCs, and this effect is ameliorated by inhibition of AKT activity but potentiated by inhibition of GSK3-ß activity. Hence, AGEs trigger HASMC calcification by regulating PI3K/AKT-GSK3-ß signaling.

9.
Food Res Int ; 146: 110454, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34119246

RESUMO

Ascidians are excellent, yet underused, marine sources of unique bioactive compounds of high nutritive content. However, reports regarding the lipid composition of ascidians are rare. In this study, using ultra-high-performance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry, we aimed to characterize the lipid profile of the tunics and inner body tissues of three species of ascidians, including Ciona intestinalis, Halocynthia roretzi, and Styela clava. We identified over 245 molecular species from 13 major lipid subclasses; glycerophospholipids (GP) and glycerolipids were the dominant lipid components in these three ascidian species (accounted for 66.30-90.60% of total lipids). Importantly, GP enriched in polyunsaturated fatty acids mainly existed in the inner body tissues of ascidians, which accounted for 18.17-32.47% of total lipids. Considering the high level of GP, we proposed that ascidians can be potentially used as health-promoting food for humans.


Assuntos
Lipidômica , Urocordados , Animais , Cromatografia Líquida de Alta Pressão , Humanos , Lipídeos , Espectrometria de Massas por Ionização por Electrospray
10.
Cell Death Differ ; 28(9): 2728-2744, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33934104

RESUMO

Macrophage accumulation and activation play an essential role in kidney fibrosis; however, the underlying mechanisms remain to be explored. By analyzing the kidney tissues from patients and animal models with kidney fibrosis, we found a large induction of PP2Acα in macrophages. We then generated a mouse model with inducible macrophage ablation of PP2Acα. The knockouts developed less renal fibrosis, macrophage accumulation, or tubular cell death after unilateral ureter obstruction or ischemic reperfusion injury compared to control littermates. In cultured macrophages, PP2Acα deficiency resulted in decreased cell motility by inhibiting Rap1 activity. Moreover, co-culture of PP2Acα-/- macrophages with tubular cells resulted in less tubular cell death attributed to downregulated Stat6-mediated tumor necrosis factor α (TNFα) production in macrophages. Together, this study demonstrates that PP2Acα promotes macrophage accumulation and activation, hence accelerates tubular cell death and kidney fibrosis through regulating Rap1 activation and TNFα production.

11.
J Altern Complement Med ; 27(9): 750-759, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33979535

RESUMO

Aims and objectives: This study evaluated the effects of a Chinese traditional qigong exercise-monkey frolic in Wuqinxi on depression and quality of life in patients with gastrointestinal cancer undergoing chemotherapy and at high risk for depression. Methods: In this prospective, randomized-controlled clinical trial, 80 patients with gastrointestinal cancer undergoing chemotherapy and at high risk for depression were randomized to an intervention group or a control group. Participants in the intervention group participated in qigong exercise five sessions each week and also received conventional treatment for 4 weeks; whereas participants in the control group received conventional treatment only. The primary outcome was the change in depressive symptoms as obtained through the Self-Rating Depression Scale. Automatic negative thoughts and quality of life were measured by the Automatic Thoughts Questionnaire and the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire-core30, respectively. Analyses were based on analysis of covariance (ANCOVA) with the "intention-to-treat" population, defined as all randomized patients by imputing mean of the column in place of missing data. Results: Seventy-nine participants (98.8%) completed the study, 40 in the intervention group and 39 in the control group. Results of ANCOVA revealed that, compared with the control group, the intervention group reported significantly lower depression scores, fewer negative thoughts, and showed significant improvement in global health status and physical, role, emotional, cognitive, and social functions (p < 0.05) following the intervention. Post-treatment scores for all symptoms in the intervention group were significantly lower than those in the control group (p < 0.05), except for financial difficulties. No significant differences between the two groups were present in the adverse events (all p > 0.05). Conclusions: Qigong exercise may be useful for relieving depression, reducing negative thoughts, and improving the quality of life in patients with gastrointestinal cancer undergoing chemotherapy. Clinical Trial Registry (#ChiCTR2100043417).

12.
Rev Cardiovasc Med ; 22(1): 231-238, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33792267

RESUMO

Trimethylamine N-oxide (TMAO) is reported to accelerate atherosclerosis and the development of adverse cardiac outcomes. Relationship between coronary atherosclerotic burden and TMAO has been examined in stable coronary artery disease and ST-segment elevation myocardial infarction, but not in non-ST-segment elevation myocardial infarction (NSTEMI). We examined the association between TMAO and coronary atherosclerotic burden in NSTEMI. In this prospective cohort study, two groups including NSTEMI (n = 73) and age-sex matched Healthy (n = 35) individuals were enrolled between 2019 and 2020. Coronary atherosclerotic burden was stratified based on the number of diseased coronary vessels and clinical risk scores including SYNTAX and GENSINI. Fasting plasma TMAO was measured by isotope dilution high-performance liquid chromatography. The median plasma TMAO levels were significantly higher in the NSTEMI group than in the Healthy group, respectively (0.59 µM; interquartile range [IQR]: 0.43-0.78 versus 0.42 µM; IQR: 0.33-0.64; P = 0.006). Within the NSTEMI group, higher TMAO levels were observed in the multivessel disease (MVD) versus single vessel disease (P = 0.002), and intermediate-high risk (score ≥ 23) versus low risk (score < 23) of SYNTAX (P = 0.003) and GENSINI (P = 0.005). TMAO level remained an independent predictor of MVD (odds ratio [OR]: 5.94, P = 0.005), intermediate-high risk SYNTAX (OR: 3.61, P = 0.013) and GENSINI scores (OR: 4.60, P = 0.008) following adjustment for traditional risk factors. Receiver operating characteristic curve (AUC) analysis for TMAO predicted MVD (AUC: 0.73, 95% confidence interval [Cl]: 0.60-0.86, P = 0.002), intermediate-high SYNTAX score (AUC: 0.70, 95% Cl: 0.58-0.82, P = 0.003) and GENSINI score (AUC: 0.70, 95% Cl: 0.57-0.83, P = 0.005). In all, TMAO levels are independently associated with high coronary atherosclerotic burden in NSTEMI.

13.
J Am Soc Nephrol ; 32(6): 1323-1337, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33771836

RESUMO

BACKGROUND: Transcriptional programs control cell fate, and identifying their components is critical for understanding diseases caused by cell lesion, such as podocytopathy. Although many transcription factors (TFs) are necessary for cell-state maintenance in glomeruli, their roles in transcriptional regulation are not well understood. METHODS: The distribution of H3K27ac histones in human glomerulus cells was analyzed to identify superenhancer-associated TFs, and ChIP-seq and transcriptomics were performed to elucidate the regulatory roles of the TFs. Transgenic animal models of disease were further investigated to confirm the roles of specific TFs in podocyte maintenance. RESULTS: Superenhancer distribution revealed a group of potential TFs in core regulatory circuits in human glomerulus cells, including FOXC1/2, WT1, and LMX1B. Integration of transcriptome and cistrome data of FOXC1/2 in mice resolved transcriptional regulation in podocyte maintenance. FOXC1/2 regulated differentiation-associated transcription in mature podocytes. In both humans and animal models, mature podocyte injury was accompanied by deregulation of FOXC1/2 expression, and FOXC1/2 overexpression could protect podocytes in zebrafish. CONCLUSIONS: FOXC1/2 maintain podocyte differentiation through transcriptional stabilization. The genome-wide chromatin resources support further investigation of TFs' regulatory roles in glomeruli transcription programs.


Assuntos
Fatores de Transcrição Forkhead/genética , Podócitos/fisiologia , Fatores de Transcrição/genética , Transcrição Genética , Animais , Diferenciação Celular/genética , Mapeamento Cromossômico , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Histonas , Humanos , Nefropatias/genética , Nefropatias/metabolismo , Proteínas com Homeodomínio LIM/genética , Proteínas com Homeodomínio LIM/metabolismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Podócitos/patologia , Fatores de Transcrição/metabolismo , Transcriptoma , Proteínas WT1/genética , Proteínas WT1/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/genética
14.
Ying Yong Sheng Tai Xue Bao ; 32(2): 649-660, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33650375

RESUMO

As one of the extreme climatic events, the frequency and intensity of drought have great impacts on regional water resource. Water is a main limiting factor for plant growth in arid and semi-arid regions. Therefore, it is of great scientific significance to explore the spatiotemporal variations and future tendency of drought for the ecological environment in the Loess Plateau. Based on grid data of monthly precipitation and temperature from 1986 to 2019, we calculated standardized precipitation evapotranspiration index (SPEI) and drought frequency. The spatiotemporal patterns and its variations were analyzed at the seasonal and annual scales in the Loess Plateau using the Mann-Kendall test and Sen's slope estimation method. Finally, the future trend of drought was analyzed in the Loess Plateau by the NAR neural network combined with Hurst index. Results showed that the trend of aridification became more significant in the Loess Plateau, and that the frequency of droughts events exhibited great spatial variations at the interannual and seasonal scales during the study period. Specifically, the highest frequency of drought in the interannual, spring and winter was found in the southeast and west of the Loess Plateau, whereas the frequency of drought in summer and autumn was higher in the northwest. The frequency of moderate drought was the highest in summer compared with other seasons while the frequency of slight drought was the highest in interannual and other seasons. The Loess Plateau showed a trend of aridification in spring and summer, but this trend in autumn and winter became weaker in most areas of the study area. The SPEI value in the interannual, spring, and summer exhibited a decline trend in a future period in the Loess Plateau. The aridification would be enhanced. The Hurst index value was the largest and the persis-tence of its change remained stronger in summer. The possibility of continuous drought in summer would be higher than that in other seasons in the future.


Assuntos
Secas , Ecossistema , China , Mudança Climática , Clima Desértico , Estações do Ano , Recursos Hídricos
15.
BMC Biol ; 19(1): 38, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627123

RESUMO

BACKGROUND: Cell type-specific transcriptional programming results from the combinatorial interplay between the repertoire of active regulatory elements. Disease-associated variants disrupt such programming, leading to altered expression of downstream regulated genes and the onset of pathological states. However, due to the non-linear regulatory properties of non-coding elements such as enhancers, which can activate transcription at long distances and in a non-directional way, the identification of causal variants and their target genes remains challenging. Here, we provide a multi-omics analysis to identify regulatory elements associated with functional kidney disease variants, and downstream regulated genes. RESULTS: In order to understand the genetic risk of kidney diseases, we generated a comprehensive dataset of the chromatin landscape of human kidney tubule cells, including transcription-centered 3D chromatin organization, histone modifications distribution and transcriptome with HiChIP, ChIP-seq and RNA-seq. We identified genome-wide functional elements and thousands of interactions between the distal elements and target genes. The results revealed that risk variants for renal tumor and chronic kidney disease were enriched in kidney tubule cells. We further pinpointed the target genes for the variants and validated two target genes by CRISPR/Cas9 genome editing techniques in zebrafish, demonstrating that SLC34A1 and MTX1 were indispensable genes to maintain kidney function. CONCLUSIONS: Our results provide a valuable multi-omics resource on the chromatin landscape of human kidney tubule cells and establish a bioinformatic pipeline in dissecting functions of kidney disease-associated variants based on cell type-specific epigenome.


Assuntos
Sistemas CRISPR-Cas , Cromatina/metabolismo , Epigenoma , Nefropatias/genética , Animais , Edição de Genes , Humanos , Peixe-Zebra
16.
J Appl Clin Med Phys ; 22(3): 55-62, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33527712

RESUMO

PURPOSE AND BACKGROUND: The magnetic resonance (MR)-only radiotherapy workflow is urged by the increasing use of MR image for the identification and delineation of tumors, while a fast generation of synthetic computer tomography (sCT) image from MR image for dose calculation remains one of the key challenges to the workflow. This study aimed to develop a neural network to generate the sCT in brain site and evaluate the dosimetry accuracy. MATERIALS AND METHODS: A generative adversarial network (GAN) was developed to translate T1-weighted MRI to sCT. First, the "U-net" shaped encoder-decoder network with some image translation-specific modifications was trained to generate sCT, then the discriminator network was adversarially trained to distinguish between synthetic and real CT images. We enrolled 37 brain cancer patients acquiring both CT and MRI for treatment position simulation. Twenty-seven pairs of 2D T1-weighted MR images and rigidly registered CT image were used to train the GAN model, and the remaining 10 pairs were used to evaluate the model performance through the metric of mean absolute error. Furthermore, the clinical Volume Modulated Arc Therapy plan was calculated on both sCT and real CT, followed by gamma analysis and comparison of dose-volume histogram. RESULTS: On average, only 15 s were needed to generate one sCT from one T1-weighted MRI. The mean absolute error between synthetic and real CT was 60.52 ± 13.32 Housefield Unit over 5-fold cross validation. For dose distribution on sCT and CT, the average pass rates of gamma analysis using the 3%/3 mm and 2%/2 mm criteria were 99.76% and 97.25% over testing patients, respectively. For parameters of dose-volume histogram for both target and organs at risk, no significant differences were found between both plans. CONCLUSION: The GAN model can generate synthetic CT from one single MRI sequence within seconds, and a state-of-art accuracy of CT number and dosimetry was achieved.


Assuntos
Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Encéfalo/diagnóstico por imagem , Humanos , Espectroscopia de Ressonância Magnética , Redes Neurais de Computação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
17.
Front Oncol ; 10: 564580, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194640

RESUMO

Purpose: To investigate an implementation method and the results of an inverse dose optimization algorithm, Gradient Based Planning Optimization (GBPO), for three-dimensional brachytherapy. Methods: The GBPO used a quadratic objective function, and a dwell time modulation item was added to the objective function to restrict the dwell time variance. We retrospectively studied 4 cervical cancer patients using different applicators and 15 cervical cancer patients using the Fletcher applicator. We assessed the plan quality of GBPO by isodose lines for the patients using different applicators. For the 15 patients using the Fletcher applicator, we utilized dose-volume histogram (DVH) parameters of HR-CTV (D100%, V150%) and organs at risk (OARs) (D0.1cc, D1cc, D2cc) to evaluate the difference between the GBPO plans and the IPSA (Inverse Planning Simulated Annealing) plans, as well as the GBPO plans and the Graphic plans. Results: For the 4 patients using different applicators, the dose distributions are conformable. For the 15 patients using the Fletcher applicator, when the dwell time modulation factor (DTMF) is less than 20, the dwell time deviation reduces quickly; however, after the DTMF increased to 100, the dwell time deviation has no remarkable change. The difference in dosimetric parameters between the GBPO plans and the IPSA plans is not statistically significant (P>0.05). The GBPO plans have a higher D100% (3.57 ± 0.36, 3.38 ± 0.34; P<0.01) and a lower V150% (55.73 ± 4.06, 57.75 ± 3.79; P<0.01) than those of the Graphic plans. The differences in other DVH parameters are negligible between the GBPO plans and the Graphic plans. Conclusions: The GBPO plans have a comparable quality as the IPSA plans and the Graphic plans for the studied cervical cancer cases. The GBPO algorithm could be integrated into a three-dimensional brachytherapy treatment planning system after studying more sites.

18.
Front Oncol ; 10: 877, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32637354

RESUMO

Objective: The prognostic nutritional index (PNI) is a significant prognostic factor in diffuse large B cell lymphoma, follicular lymphoma, and other malignancies. The current study aimed to explore its prognostic role in extranodal natural killer/T cell lymphoma (ENKTL). Methods: Patients diagnosed with ENKTL and treated during 2002 and 2018 (n = 184) were retrospectively recruited. PNI was calculated from albumin concentration (g/L) and total lymphocyte count (*109/L). The association of PNI and overall survival (OS) or progression-free survival (PFS) was assessed in univariate analysis and multivariate Cox regression validated by the 10-fold cross-validation method. Results: Survival analyses showed that both OS and PFS differed significantly between PNI groups stratified by a cutoff value of 49.0. The 3- and 5-year OS were 42.5 and 36.3% in the low-PNI (PNI < 49) subgroup and 70.6% and 63.9% (P < 0.001) in the high-PNI (PNI ≥ 49) subgroup, respectively. The corresponding PFS showed a similar pattern (38.4, 32.4 vs. 64.8, 54.0%, P < 0.001). Multivariate analysis indicated that PNI was significantly independent for both OS (HR = 0.517, 95% CI = 0.322-0.831, P = 0.006) and PFS (HR = 0.579, 95% CI = 0.373-0.899, P = 0.015). Furthermore, integrating PNI into the models of IPI (International Prognostic Index), KPI (Korean Prognostic Index), and PINK (prognostic index of natural killer lymphoma) could improve the area under the curve (AUC) and reduce the integrated Brier score (IBS) and Akaike Information Criterion (AIC) value of each model. Conclusion: PNI was a significant prognostic indicator for ENKTL.

19.
Cell Death Discov ; 6: 40, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32528729

RESUMO

Our previous study demonstrated that the mammalian target of rapamycin complex 2 (mTORC2) signaling alleviates renal inflammation and protects against cisplatin-induced AKI. However, the underlying mechanisms for mTORC2 in regulating renal inflammation in AKI remain to be determined. In this study, we found that lipopolysaccharide (LPS) could activate mTORC2 signaling in NRK-52E cells, and blockage of mTORC2 signaling led to Yap/Taz degradation, which in turn activated NF-κB signaling and induced inflammatory cytokines secretion. Overexpression of constitutively active Taz (Taz-S89A) could attenuate the inflammation-amplified role of mTORC2 blockage. In mouse models, tubule-specific deletion of Rictor had higher blood urea nitrogen level, severe morphological injury as well as more inflammatory cells accumulation compared with those in their littermate controls. Overall, these results demonstrate that mTORC2 signaling protects against renal inflammation and dictates the outcome of AKI by modulating Yap/Taz degradation.

20.
Cell Death Dis ; 11(5): 364, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404875

RESUMO

Ras homolog enriched in brain (Rheb1), a small GTPase, plays a crucial role in regulating cell growth, differentiation, and survival. However, the role and mechanisms for Rheb1 in tubular cell survival and acute kidney injury (AKI) remain unexplored. Here we found that Rheb1 signaling was activated in kidney tubule of AKI patients and cisplatin-treated mice. A mouse model of tubule-specific deletion of Rheb1 (Tubule-Rheb1-/-) was generated. Compared to control littermates, Tubule-Rheb1-/- mice were phenotypically normal within 2 months after birth but developed more severe kidney dysfunction, tubular cell death including apoptosis, necroptosis and ferroptosis, mitochondrial defect and less PGC-1α expression after cisplatin injection. In primary cultured tubular cells, Rheb1 ablation exacerbated cisplatin-induced cell death and mitochondrial defect. Furthermore, haploinsufficiency for Tsc1 in tubular cells led to Rheb1 activation and mitigated cisplatin-induced cell death, mitochondrial defect and AKI. Together, this study uncovers that Rheb1 may protect against cisplatin-induced tubular cell death and AKI through maintaining mitochondrial homeostasis.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Morte Celular/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Proteína Enriquecida em Homólogo de Ras do Encéfalo/metabolismo , Injúria Renal Aguda/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Cisplatino/farmacologia , Homeostase/fisiologia , Rim/efeitos dos fármacos , Rim/metabolismo , Túbulos Renais/metabolismo , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Substâncias Protetoras/farmacologia
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