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1.
J Mol Cell Cardiol ; 192: 79-93, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38761990

RESUMO

Ferroptosis is an iron-dependent programmed cell death form resulting from lipid peroxidation damage, it plays a key role in organ damage and tumor development from various causes. Sepsis leads to severe host response after infection with high mortality. The long non-coding RNAs (LncRNAs) are involved in different pathophysiological mechanisms of multiple diseases. Here, we used cecal ligation and puncture (CLP) operation to mimic sepsis induced myocardial injury (SIMI) in mouse model, and LncRNAs and mRNAs were profiled by Arraystar mouse LncRNA Array V3.0. Based on the microarray results, 552 LncRNAs and 520 mRNAs were differentially expressed in the sham and CLP groups, among them, LncRNA Lcn2-204 was the highest differentially expressed up-regulated LncRNA. Iron metabolism disorder was involved in SIMI by bioinformatics analysis, meanwhile, myocardial iron content and lipocalin-2 (Lcn2) protein expressions were increased. The CNC network comprised 137 positive interactions and 138 negative interactions. Bioinformatics analysis showed several iron-related terms were enriched and six genes (Scara5, Tfrc, Lcn2, Cp, Clic5, Ank1) were closely associated with iron metabolism. Then, we constructed knockdown LncRNA Lcn2-204 targeting myocardium and found that it ameliorated cardiac injury in mouse sepsis model through modulating iron overload and ferroptosis. In addition, we found that LncRNA Lcn2-204 was involved in the regulation of Lcn2 expression in septic myocardial injury. Based on these findings, we conclude that iron overload and ferroptosis are the key mechanisms leading to myocardial injury in sepsis, knockdown of LncRNA Lcn2-204 plays the cardioprotective effect through inhibition of iron overload, ferroptosis and Lcn2 expression. It may provide a novel therapeutic approach to ameliorate sepsis-induced myocardial injury.

2.
Food Chem ; 449: 139207, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38579655

RESUMO

Tetrastigma hemsleyanum root is a popular functional food in China, and the price varies based on the origin of the product. The link between the origin, metabolic profile, and bioactivity of T. hemsleyanum must be investigated. This study compares the metabolic profiles of 254 samples collected from eight different areas with 49 potential key chemical markers using plant metabolomics. The metabolic pathways of the five critical flavonoid metabolites were annotated and enriched using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Moreover, a random forest model aiding the spectrum-effect relationship analysis was developed for the first time indicating catechin and darendoside B as potential quality markers of antioxidant activity. The findings of this study provide a comprehensive understanding of the chemical composition and bioactive compounds of T. hemsleyanum as well as valuable information on the evaluation of the quality of various samples and products in the market.


Assuntos
Metabolômica , Raízes de Plantas , Vitaceae , Vitaceae/química , Vitaceae/metabolismo , Vitaceae/genética , Raízes de Plantas/química , Raízes de Plantas/metabolismo , China , Extratos Vegetais/química , Flavonoides/análise , Flavonoides/química , Flavonoides/metabolismo , Antioxidantes/metabolismo , Antioxidantes/química , Antioxidantes/análise
3.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38285605

RESUMO

This study was conducted to investigate the effects of sodium butyrate (SB) supplementation on growth performance, intestinal barrier functions, and intestinal bacterial communities in sucking lambs. Forty lambs of 7 d old, with an average body weight (BW) of 4.46 ±â€…0.45 kg, were allocated into the control (CON) or SB group, with each group having five replicate pens (n = 5). Lambs were orally administered SB at 1.8 mL/kg BW in the SB group or the same volume of saline in the CON group. Treatments were administered from 7 to 35 d of age, when one lamb from each replicate was slaughtered to obtain intestinal tissues and contents. The results showed that supplementation with SB tended to increase the BW (P = 0.079) and the starter intake (P = 0.089) of lambs at 35 d of age. The average daily gain of lambs in the SB group was significantly greater than that in the CON group (P < 0.05). The villus height of jejunum in the SB group was markedly higher (P < 0.05) than that in the CON group. In ileum, lambs in the SB group had lower (P < 0.05) crypt depth and greater (P < 0.05) villus-to-crypt ratio than those in the CON group. Compared with the CON group, the mRNA and protein expressions of Claudin-1 and Occludin were increased (P < 0.05) in the SB group. Supplementation with SB decreased the relative abundances of pathogenic bacteria, including Clostridia_UCG-014 (P = 0.094) and Romboutsia (P < 0.05), which were negatively associated with the intestinal barrier function genes (P < 0.05). The relative abundance of Succiniclasticum (P < 0.05) was higher in the SB group, and it was positively correlated with the ratio of villi height to crypt depth in the jejunum (P < 0.05). Compared with the CON group, the function "Metabolism of Cofactors and Vitamins" was increased in the SB group lambs (P < 0.05). In conclusion, SB orally administration during suckling period could improve the small intestine development and growth performance of lambs by inhibiting the harmful bacteria (Clostridia_UCG-014, Romboutsia) colonization, and enhancing intestinal barrier functions.


It is well known that butyrate and its derivatives have various benefits for the rumen development of ruminants, whereas its effects on the small intestine in preweaned lambs have received little attention. Therefore, the present study investigated the effects of sodium butyrate (SB) supplementation on growth performance, intestinal barrier functions, and intestinal bacterial communities in sucking lambs. The results indicated that SB dietary treatment has beneficial effects on the small intestine development and growth performance of suckling lambs.


Assuntos
Intestino Delgado , Intestinos , Animais , Ovinos , Ácido Butírico/farmacologia , Mucosa Intestinal/metabolismo , Carneiro Doméstico , Peso Corporal , Ração Animal/análise , Suplementos Nutricionais , Dieta/veterinária
4.
Shock ; 61(3): 360-366, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38117132

RESUMO

ABSTRACT: Objective : This study aimed to investigate whether changes in carotid artery corrected flow time (ΔFTc bolus ) and carotid artery peak flow velocity respiratory variation (Δ V peak bolus ) induced by the fluid challenge could reliably predict fluid responsiveness in mechanically ventilated patients with a tidal volume < 8 mL/kg Predicted Body Weight while preserving spontaneous breathing. Methods : Carotid artery corrected flow time, Δ V peak, and hemodynamic data were measured before and after administration of 250 mL crystalloids. Fluid responsiveness was defined as a 10% or more increase in stroke volume index as assessed by noninvasive cardiac output monitoring after the fluid challenge. Results : A total of 43 patients with acute circulatory failure were enrolled in this study. Forty-three patients underwent a total of 60 fluid challenges. The ΔFTc bolus and Δ V peak bolus showed a significant difference between the fluid responsiveness positive group (n = 35) and the fluid responsiveness negative group (n = 25). Spearman correlation test showed that ΔFTc bolus and Δ V peak bolus with the relative increase in stroke volume index after fluid expansion ( r = 0.5296, P < 0.0001; r = 0.3175, P = 0.0135). Multiple logistic regression analysis demonstrated that ΔFTc bolus and Δ V peak bolus were significantly correlated with fluid responsiveness in patients with acute circulatory failure. The areas under the receiver operating characteristic curves of ΔFTc bolus and Δ V peak bolus for predicting fluid responsiveness were 0.935 and 0.750, respectively. The optimal cutoff values of ΔFTc bolus and Δ V peak bolus were 0.725 (sensitivity = 97.1%, specificity = 84%) and 4.21% (sensitivity = 65.7%, specificity = 80%), respectively. Conclusion : In mechanically ventilated patients with a tidal volume < 8 mL/kg while preserving spontaneous breathing, ΔFTc bolus and Δ V peak bolus could predict fluid responsiveness. The predictive performance of ΔFTc bolus was superior to Δ V peak bolus .


Assuntos
Respiração Artificial , Choque , Humanos , Respiração Artificial/métodos , Volume de Ventilação Pulmonar , Hidratação/métodos , Hemodinâmica , Volume Sistólico , Artérias Carótidas/diagnóstico por imagem
5.
Opt Lett ; 48(17): 4476-4479, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37656532

RESUMO

This Letter introduces the idea of unsupervised learning into object-independent wavefront sensing for the first time, to the best of our knowledge, which can achieve fast phase recovery of arbitrary objects without labels. First, a fine feature extraction method which only depends on the wavefront aberrations is proposed. Then, a lightweight neural network and an optical feature system are combined to form an unsupervised learning model, and the neural network is promoted to be well trained by reversely outputting fine features. Simulation results prove that the proposed method can effectively overcome the aberrations (static or variable) existing in the optical system and achieve wavefront sensing of different objects with high precision and efficiency.

6.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 35(7): 684-689, 2023 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-37545443

RESUMO

OBJECTIVE: To observe the ferroptosis triggered by in different pathways during cecal ligation and puncture (CLP)-induced liver injury in septic mice, and to investigate whether mitochondrial aldehyde dehydrogenase 2 (ALDH2) can alleviate sepsis-induced liver injury by inhibiting ferroptosis. METHODS: Sixty 8-week-old male C57BL/6J mice were randomly divided into sham operation group (Sham group), CLP group, ferroptosis inhibitor ferrostain-1 (Fer-1) group, ALDH2-specific agonist Alda-1 group, iron chelator deferasirox Fe3+ chelate (DXZ) group and dimethyl sulfoxide (DMSO) group, with 10 mice in each group. The septic liver injury was induced by CLP in mice model. In the Sham group, only laparotomy was performed without ligation and puncture of the cecum. 10 mL/kg 5% DMSO, 5 mg/kg Fer-1, 50 mg/kg DXZ and 10 mg/kg Alda-1 were injected intraperitoneally 1 hour before CLP in the DMSO, Fer-1, DXZ and Alda-1 groups respectively. At 24 hours after operation, eyeball blood and liver tissue were collected from anesthetized mice. The hepatic structure and inflammatory infiltration were observed by hematoxylin-eosin (HE) staining. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in serum, the levels of hepatic malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS) were detected. Western blotting was used to detect the protein expressions of ALDH2, ferroptosis-related proteins glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1) and transferrin receptor 1 (TFR1) in liver tissue. RESULTS: Compared with Sham group, the mice in CLP group showed varying degrees of congestion, disorganized hepatocyte arrangement, inflammatory cell infiltration at 24 hours after operation. Compared with the CLP group, the mice in the Fer-1 group, DXZ group and Alda-1 group liver morphology, liver injury and inflammatory cell infiltration was improved. Compared with Sham group, the serum levels of ALT and AST, the contents of MDA and ROS, and the expression of TFR1 protein in CLP group were significantly increased, while the activity of SOD and the expressions of ALDH2, GPX4 and FSP1 protein in CLP group were significantly decreased. Compared with CLP group, serum ALT and AST levels in Fer-1, DXZ and Alda-1 groups were significantly decreased [ALT (U/L): 45.76±10.81, 37.30±2.98, 36.40±12.75 vs. 73.06±12.20, AST (U/L): 61.57±2.69, 52.41±6.92, 56.05±8.29 vs. 81.59±5.46, all P < 0.05], and the contents of MDA, ROS and TFR1 protein expression in liver tissue were significantly decreased [MDA (µmol/L): 0.60±0.10, 0.57±0.18, 0.83±0.39 vs. 1.61±0.30, ROS (fluorescence intensity): 270.34±9.64, 276.02±62.33, 262.05±18.55 vs. 455.38±36.07, TFR1/GAPDH: 0.90±0.04, 1.01±0.09, 0.55±0.08 vs. 1.18±0.06, all P < 0.05], and the SOD activity and ALDH2, GPX4 and FSP1 protein expressions in liver tissue were significantly increased [SOD (kU/g): 88.77±8.20, 88.37±4.47, 93.43±7.24 vs. 50.27±3.57, ALDH2/GAPDH: 1.10±0.15, 1.02±0.07, 1.14±0.07 vs. 0.70±0.04, GPX4/GAPDH: 1.02±0.12, 0.99±0.08, 1.05±0.19 vs. 0.71±0.10, FSP1/GAPDH: 1.06±0.24, 1.02±0.08, 0.93±0.09 vs. 0.66±0.03, all P < 0.05]. There was no significant difference in the parameters between DMSO group and CLP group. CONCLUSIONS: Both GPX4 and FSP1 mediated ferroptosis are involved in liver injury in septic mice. Activation of ALDH2 and inhibition of ferroptosis can alleviatehepatic injury. ALDH2 may play a protective role by regulating FSP1 and GPX4 mediated ferroptosis.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Ferroptose , Sepse , Camundongos , Masculino , Animais , Aldeído-Desidrogenase Mitocondrial , Espécies Reativas de Oxigênio , Dimetil Sulfóxido , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
7.
Artigo em Inglês | MEDLINE | ID: mdl-37182408

RESUMO

Ultrafiltration-high performance liquid chromatography (UF-HPLC) and high resolution biochromatogram (HR-biochromatogram), have been proven to be effective methods for the rapid discovery of enzyme inhibitors in natural medicines. In attempt to conquer false-positive and false- negative screening results, a new multi-stage strategy based on the complementarity of UF-HPLC and HR-biochromatogram has been proposed for the fast screening of tyrosinase inhibitory components using the fibrous root of Bletilla striata as a case study. For the first two stages, UF- HPLC and HR-biochromatogram, were applied individually for the screening of high-affinity tyrosinase ligands and tyrosinase inhibitors. After that, the inconsistent results, which yielded two potential active fractions, indicated a third stage screening. Thus, a "strengthen" biochromatogram was established to microfractionate the concentrated extract and further evaluate the tyrosinase inhibitors. The complementarity nature of two different screening methods was firstly explored to distinguish tyrosinase inhibitors from the fibrous root of Bletilla striata. As a result, four compounds were screened, isolated and characterized as new potent tyrosinase inhibitors. The screening results were verified by tyrosinase inhibition assays, melanin inhibitory in zebrafish and molecular docking. All compounds possessed much higher tyrosinase inhibition than α-arbutin, especially, 1-(4- Hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene-2,7-diol demonstrated stronger tyrosinase inhibition than kojic acid. This study presented a new screening strategy which had a great potential in rapidly and efficiently exploring tyrosinase inhibitors in complex mixtures. Moreover, it is the first time to reveal the skin-whitening nature of the fibrous root of B. striata, which indicating the promising prospect in the full utilization of B. striata plant.


Assuntos
Monofenol Mono-Oxigenase , Orchidaceae , Animais , Monofenol Mono-Oxigenase/química , Ultrafiltração/métodos , Simulação de Acoplamento Molecular , Peixe-Zebra , Inibidores Enzimáticos/química
8.
PeerJ ; 11: e14767, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36718444

RESUMO

Background: Ferroptosis and long-noncoding RNAs (lncRNAs) play crucial roles in doxorubicin (DOX)-induced myocardial injury (DIMI). Nevertheless, there is no research to construct competing endogenous RNAs (ceRNAs) network between lncRNAs and ferroptosis-related key gene. So our research was designed to screen ferroptosis-related genes from differentially expressed mRNAs in DIMI and construct lncRNAs regulated ferroptosis-related key gene ceRNAs network. Methods: The male mice were injected with DOX intraperitoneally to induce myocardial injury, myocardial injury was evaluated by hematoxylin and eosin (HE) staining, and ferroptosis-related protein-glutathione peroxidase 4 (GPx4) protein expression was detected. The differentially expressed lncRNAs and mRNAs were detected by microarray, and the ferroptosis-related genes were screened to construct a protein-protein associations (PPA) network, the highest maximal clique centrality (MCC) score gene were identified by Cytoscape software, miRNAs bound to key genes and lncRNAs bound to miRNAs were predicted; then, the obtained lncRNAs were intersected with differentially expressed lncRNAs detected by microarray. Finally, the lncRNA/miRNA/mRNA ceRNA network of the highest MCC score gene regulating ferroptosis in DIMI was constructed. The expressions of the key components in ceRNA network were detected by qRT-PCR. Results: Compared with the control group, in the DOX group, myocardial enzymes and HE staining showed that myocardium structure was changed, and GPx4 protein expression was decreased. The differentially expressed 10,265 lncRNAs and 6,610 mRNAs in the DOX group were detected via microarray. Among them, 114 ferroptosis-related genes were obtained to construct PPA networks, and Becn1 was identified as the key gene. Finally, the ceRNA network including Becn1, three miRNAs and four lncRNAs was constructed by predicting data of the Starbase database. The relative expressions of these components in ceRNA net were up-regulated and consistent with microarray results. Conclusions: Based on the microarray detection results and bioinformatics analysis, we screened ferroptosis-related gene Becn1 and constructed the lncRNA/miRNA/mRNA ceRNA network of regulated ferroptosis in DIMI.


Assuntos
Ferroptose , MicroRNAs , Miocárdio , RNA Longo não Codificante , Animais , Masculino , Camundongos , Doxorrubicina/efeitos adversos , Ferroptose/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Miocárdio/patologia
10.
Quant Imaging Med Surg ; 11(7): 2918-2932, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34249623

RESUMO

BACKGROUND: This study classifies lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) using subregion-based radiomics features extracted from positron emission tomography/computed tomography (PET/CT) images. METHODS: In this study, the standard 18F-fluorodeoxyglucose (FDG) PET/CT images of 150 patients with lung ADC and 100 patients with SCC were retrospectively collected from the PET Center of the First Affiliated Hospital, College of Medicine, Zhejiang University. First, the 3D feature vector of each tumor voxel (whose basis is PET value, CT value, and CT local dominant orientation) was extracted. Using K-means individual clustering and population clustering, each tumor was divided into 4 subregions that reflect intratumoral regional heterogeneity. Next, based on each subregion, 385 radiomics features were extracted. Clinical features including age, gender, and smoking history were included. Thus, there were a total of 1,543 features extracted from PET/CT images and clinical reports. Statistical tests were then used to eliminate irrelevant and redundant features, and the recursive feature elimination (RFE) algorithm was used to select the best feature subset to classify SCC and ADC. Finally, 7 types of classifiers were tested to achieve the optimized model for the classification: support vector machine (SVM) with linear kernel, SVM with radial basis function kernel (SVM-RBF), random forest, logistic regression, Gaussian process classifier, linear discriminant analysis, and the AdaBoost classifier. Furthermore, 5-fold cross-validation was applied to obtain the sensitivity, specificity, accuracy, and area under the curve (AUC) for performance evaluation. RESULTS: Our model exhibited the best performance with the subregion radiomics features and SVM-RBF classifier, with a 5-fold cross-validation sensitivity, specificity, accuracy, and AUC of 0.8538, 0.8758, 0.8623, and 0.9155, respectively. The interquartile range feature from subregion 2 of CT and the gender feature from the clinical reports are the 2 optimized features that achieved the highest comprehensive score. CONCLUSIONS: Our proposed model showed that SCC and ADC could be classified successfully using PET/CT images, which could be a promising tool to assist radiologists or medical physicists during diagnosis. The subregion-based method illustrated that non-small cell lung cancer (NSCLC) depicts intratumoral regional heterogeneity on both CT and PET images. By defining these heterogeneities through a subregion-based method, the diagnostic performance was improved. The 3D feature vector (whose basis is PET value, CT value, and CT local dominant orientation) showed superiority in reflecting NSCLC intratumoral regional heterogeneity.

11.
Opt Express ; 29(12): 18669-18687, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34154119

RESUMO

Aberrations degrade the accuracy of quantitative, imaging-based measurements, like particle image velocimetry (PIV). Adaptive optical elements can in principle correct the wavefront distortions, but are limited by their technical specifications. Here we propose an actuator-free correction based on a multiple-input deep convolutional neural network which uses an additional input from a wavefront sensor to correct time-varying distortions. It is applied for imaging flow velocimetry to conduct measurements through a fluctuating air-water phase boundary. Dataset for neural network is generated by an experimental setup with a deformable mirror. Correction performance of trained model is estimated in terms of image quality, which is improved significantly, and flow measurement results, where the errors induced by the distortion from fluctuating phase boundary can be corrected by 82 %. The technique has the potential to replace classical closed-loop adaptive optical systems where the performance of the actuators is not sufficient.

12.
Phys Med Biol ; 66(11)2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-33882466

RESUMO

Positron emission tomography (PET) is a promising medical imaging technology that provides non-invasive and quantitative measurement of biochemical process in the human bodies. PET image reconstruction is challenging due to the ill-poseness of the inverse problem. With lower statistics caused by the limited detected photons, low-dose PET imaging leads to noisy reconstructed images with much quality degradation. Recently, deep neural networks (DNN) have been widely used in computer vision tasks and attracted growing interests in medical imaging. In this paper, we proposed a maximuma posteriori(MAP) reconstruction algorithm incorporating a convolutional neural network (CNN) representation in the formation of the prior. Rather than using the CNN in post-processing, we embedded the neural network in the reconstruction framework for image representation. Using the simulated data, we first quantitatively evaluated our proposed method in terms of the noise-bias tradeoff, and compared with the filtered maximum likelihood (ML), the conventional MAP, and the CNN post-processing methods. In addition to the simulation experiments, the proposed method was further quantitatively validated on the acquired patient brain and body data with the tradeoff between noise and contrast. The results demonstrated that the proposed CNN-MAP method improved noise-bias tradeoff compared with the filtered ML, the conventional MAP, and the CNN post-processing methods in the simulation study. For the patient study, the CNN-MAP method achieved better noise-contrast tradeoff over the other three methods. The quantitative enhancements indicate the potential value of the proposed CNN-MAP method in low-dose PET imaging.


Assuntos
Processamento de Imagem Assistida por Computador , Tomografia por Emissão de Pósitrons , Algoritmos , Encéfalo/diagnóstico por imagem , Humanos , Redes Neurais de Computação
13.
Int Immunopharmacol ; 94: 107459, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33611061

RESUMO

Wear debris-induced osteoclast accumulation around implants plays a crucial role during the progression of periprosthetic osteolysis (PPO). We have confirmed that acetyl-11-keto-ß-boswellic acid (AKBA) promotes bone formation and protects against particle-induced bone destruction in vivo. However, the effect of AKBA on titanium-induced bone resorption is unknown. In this study, we detected the inhibitory effect of AKBA on titanium-induced bone erosion in vivo and used RAW264.7 cells and bone marrow macrophages (BMMs) to investigate the effect and underlying mechanism of AKBA on the differentiation and resorptive function of osteoclasts. Our findings revealed that AKBA inhibited particle-induced bone loss and osteoclast formation in vivo. Furthermore, AKBA exerted inhibitory effects on RANKL-induced osteoclastogenesis, osteoclastic ring-dependent resorption and the expression of osteoclast marker genes via the ERK signaling pathway in vitro. Our data further established the protective effect of AKBA on titanium particle-induced bone erosion from a new perspective of bone erosion prevention, strongly confirming that AKBA is an appropriate agent for protection against PPO.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Triterpenos/uso terapêutico , Animais , Conservadores da Densidade Óssea/farmacologia , Regulação para Baixo/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/efeitos dos fármacos , Osteoclastos/fisiologia , Osteogênese/efeitos dos fármacos , Osteólise/induzido quimicamente , Osteólise/tratamento farmacológico , Células RAW 264.7 , Crânio , Titânio , Triterpenos/farmacologia
14.
Hum Exp Toxicol ; 40(5): 735-741, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33073623

RESUMO

OBJECTIVES: Increasing evidence suggests that heat shock protein 70 (Hsp70) has a protective effect in sepsis-induced cardiomyopathy; however, the protective mechanism remains unclear. METHODS: Previous studies have also implicated autophagy in sepsis-induced cardiomyopathy. The aim of the current study was to reveal the protective mechanisms of Hsp70 in sepsis-induced cardiomyopathy using a cecal ligation and puncture (CLP) rat sepsis model. The roles of Hsp70 and autophagy in sepsis-induced cardiomyopathy were investigated by pretreating rats with the Hsp70 inhibitor quercetin or the autophagy inhibitor 3-methyladenine (3-Ma) before CLP. We also investigated the protective mechanisms of Hsp70 and the relationship between Hsp70 and autophagy in vitro by stimulating H9c2 cells with lipopolysaccharide (LPS) to simulate sepsis. RESULTS: The result show that inhibition of Hsp70 promoted sepsis-induced death in rats, while inhibition of autophagy inhibited sepsis-induced death. These results suggested that both Hsp70 and autophagy were involved in sepsis-induced cardiomyopathy. Overexpression of Hsp70 in H9c2 myocardial cells in vitro suppressed LPS-induced apoptosis, while inhibition of autophagy with 3-Ma also decreased LPS-induced H9c2 cell apoptosis, suggesting that the protective effect of Hsp70 in sepsis-induced cardiomyopathy was related to autophagy regulation. CONCLUSION: Overall, these results suggested that Hsp70 protected against sepsis-induced cardiac impairment by attenuating sepsis-induced autophagy.


Assuntos
Autofagia/efeitos dos fármacos , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP70/uso terapêutico , Sepse/complicações , Adenina/análogos & derivados , Adenina/metabolismo , Animais , Cardiomiopatias/etiologia , Humanos , Masculino , Modelos Animais , Quercetina/metabolismo , Ratos , Ratos Sprague-Dawley , Sepse/metabolismo
15.
Ann Transl Med ; 8(17): 1053, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33145272

RESUMO

BACKGROUND: The aim of the study was to identify the clinical features and the factors associated with burn induced mortality among young adults after exposure to indoor explosion and fire. METHODS: This is an observational study which included burn patients who were admitted to eighteen ICUs after a fire disaster. Epidemiologic and clinical characteristics, as well as therapy were recorded. The primary outcome was 90-day mortality. The mortality-related factors were also analyzed. RESULTS: There were 167 burn patients enrolled in the study, the median age was 38 years, 62 (37.1%) patients died within 90 days. Seventy-one percent of patients had a burn size ≥90% TBSA, and 73.7% of patients had a full-thickness burn area above 50% TBSA. The survivors had lower Baux scores, and received earlier escharectomy and autologous skin grafts. The 50% mortality rates (LA50s) for burn size and full-thickness burn area were 95.8% and 88.6% TBSA, respectively. The multivariate analysis showed that full-thickness burn area over 50% TBSA and residual burned surface area (RBSA)/TBSA at 28 days were strong predictors of mortality among burn patients (odds ratio 2.55; 95% CI, 1.01 to 6.44, P=0.047; odds ratio 1.07; 95% CI, 1.04 to 1.09, P<0.001). The ROC curve-based cut-off values of RBSA/TBSA at 28 days for predicting 90-day mortality were 62.5%. CONCLUSIONS: Burn size and full-thickness burn area were the main risk factors for poor outcome in patients with extensive burns. Earlier escharectomy and autologous skin grafts may improve outcomes.

16.
Comput Methods Programs Biomed ; 197: 105764, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33010702

RESUMO

BACKGROUND AND OBJECTIVES: Attenuation correction is important for PET image reconstruction. In clinical PET/CT scans, the attenuation information is usually obtained by CT. However, additional CT scans for delayed PET imaging may increase the risk of cancer. In this paper, we propose a novel CT generation method for attenuation correction in delayed PET imaging that requires no additional CT scans. METHODS: As only PET raw data is available for the delayed PET scan, routine image registration methods are difficult to use directly. To solve this problem, a reconstruction network is developed to produce pseudo PET images from raw data first. Then a second network is used to generate the CT image through mapping PET/CT images from the first scan to the delayed scan. The inputs of the second network are the two pseudo PET images from the first and delayed scans, and the CT image from the first scan. The labels are taken from the ground truth CT image in the delayed scan. The loss function contains an image similarity term and a regularization term, which reflect the anatomy matching accuracy and the smoothness of the non-rigid deformation field, respectively. RESULTS: We evaluated the proposed method with simulated and clinical PET/CT datasets. Standard Uptake Value was computed and compared with the gold standard (with coregistered CT for attenuation correction). The results show that the proposed supervised learning method can generate PET images with high quality and quantitative accuracy. For the test cases in our study, the average MAE and RMSE of the proposed supervised learning method were 4.61 and 22.75 respectively, and the average PSNR between the reconstructed PET image and the ground truth PET image was 62.13 dB. CONCLUSIONS: The proposed method is able to generate accurate CT images for attenuation correction in delayed PET scans. Experiments indicate that the proposed method outperforms traditional methods with respect to quantitative PET image accuracy.


Assuntos
Processamento de Imagem Assistida por Computador , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Aprendizado de Máquina Supervisionado , Tomografia Computadorizada por Raios X
17.
PLoS One ; 15(9): e0238455, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32886683

RESUMO

PET is a popular medical imaging modality for various clinical applications, including diagnosis and image-guided radiation therapy. The low-dose PET (LDPET) at a minimized radiation dosage is highly desirable in clinic since PET imaging involves ionizing radiation, and raises concerns about the risk of radiation exposure. However, the reduced dose of radioactive tracers could impact the image quality and clinical diagnosis. In this paper, a supervised deep learning approach with a generative adversarial network (GAN) and the cycle-consistency loss, Wasserstein distance loss, and an additional supervised learning loss, named as S-CycleGAN, is proposed to establish a non-linear end-to-end mapping model, and used to recover LDPET brain images. The proposed model, and two recently-published deep learning methods (RED-CNN and 3D-cGAN) were applied to 10% and 30% dose of 10 testing datasets, and a series of simulation datasets embedded lesions with different activities, sizes, and shapes. Besides vision comparisons, six measures including the NRMSE, SSIM, PSNR, LPIPS, SUVmax and SUVmean were evaluated for 10 testing datasets and 45 simulated datasets. Our S-CycleGAN approach had comparable SSIM and PSNR, slightly higher noise but a better perception score and preserving image details, much better SUVmean and SUVmax, as compared to RED-CNN and 3D-cGAN. Quantitative and qualitative evaluations indicate the proposed approach is accurate, efficient and robust as compared to other state-of-the-art deep learning methods.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Tomografia por Emissão de Pósitrons/métodos , Algoritmos , Encéfalo , Aprendizado Profundo , Humanos , Redes Neurais de Computação , Doses de Radiação , Radioterapia Guiada por Imagem , Razão Sinal-Ruído , Aprendizado de Máquina Supervisionado , Tomografia Computadorizada por Raios X/métodos
18.
Biosci Biotechnol Biochem ; 84(12): 2458-2465, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32841583

RESUMO

This study aimed to identify the role of lncRNA TUG1 with miR-221-3p on mice with lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS). Animal model was established, and lung tissue histopathologic status and permeability were detected by hematoxylin-eosin (HE) or Evans blue dye assay respectively. Levels of inflammation cytokines, lncRNA TUG1, miR-221-3p, sprouty related EVH1 domain-containing 2 (SPRED2), and phosphorylated (p)-ERK1/2 were determined by ELISA, qRT-PCR or Western blot. Pulmonary impairment and apoptosis were examined by flow cytometry. We observed that LPS up-regulated levels of tumor necrosis factor-α (TNF-α), Interleukin-1ß (1L-1ß), and ERK1/2 phosphorylation, and reduced SPRED2 levels, which were rescued by overexpressed lncRNA TUG1. StarBase and dual-luciferase reporter assay verified that miR-221-3p was targeted by lncRNA TUG1. MiR-221-3p could reverse the effect of lncRNA TUG1 on cell apoptosis, levels of TNF-α, IL-1ß, SPRED2, and p-ERK1/2. Therefore, overexpressed lncRNA TUG1 attenuated LPS-induced pulmonary impairment in ARDS mice via regulating miR-221-3p/SPRED2 axis.


Assuntos
Apoptose/genética , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , MicroRNAs/genética , RNA Longo não Codificante/genética , Proteínas Repressoras/metabolismo , Animais , Apoptose/efeitos dos fármacos , Contagem de Células , Feminino , Inflamação/genética , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Neutrófilos/citologia , Células RAW 264.7
19.
J Int Med Res ; 48(8): 300060520947916, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32790508

RESUMO

OBJECTIVE: This study investigated whether the CYP11B2 -344T/C polymorphism is correlated with transient ischemic attack (TIA) susceptibility. METHODS: We recruited 100 TIA patients and 100 control subjects and analyzed the CYP11B2 -344T/C polymorphism using restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency in TIA patients and controls was 42% compared with 48% for TT genotypes, 51% compared with 45% for TC genotypes, and 7% compared with 7% for CC genotype, respectively. Allele frequencies in TIA patients and controls were 67.5% compared with 70.5% for T-allele and 32.5% compared with 29.5% for C-allele, respectively. No association between the CYP11B2 -344T/C polymorphism and TIA was observed in all comparisons. CONCLUSION: Our data suggest that there was no association between the CYP11B2 -344T/C polymorphism and TIA in a Chinese population.


Assuntos
Hipertensão , Ataque Isquêmico Transitório , China , Citocromo P-450 CYP11B2/genética , Frequência do Gene , Genótipo , Humanos , Ataque Isquêmico Transitório/genética , Polimorfismo Genético
20.
Neurosci Lett ; : 135199, 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32585254

RESUMO

This article has been withdrawn at the request of the Editor-in-Chief. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

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