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1.
Opt Express ; 30(17): 31381-31395, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36242221

RESUMO

Bifurcation detection in coronary arteries is significant since it influences the treatment strategy selection and optimization. Bifurcations are also reliable landmarks for image registration. Intravascular optical coherence tomography (IVOCT) is a high-resolution imaging modality that is very useful in percutaneous coronary intervention stenting optimization. We present a bifurcation identification method utilizing pullback characteristics for IVOCT, which can effectively identify the bifurcations with a small size. The longitudinal view of the pullback will appear as an outward discontinuity in the bifurcation area. By detecting this discontinuity, bifurcation can be identified with high accuracy. We also use the normal vectors method to extract the ostium of bifurcation. We compare the proposed method with the widely-used distance transformation method by clinical 5302 IVOCT images from 22 pullbacks. The average metrics of true positive rate (TPR), true negative rate (TNR), positive predictive value (PPV), and negative predictive value (NPV) for the proposed method are 86.97%, 98.50%, 85.56%, and 98.67%, respectively. TPR, PPV, and NPV by the proposed method are improved by 40.24%, 9.31%, 3.90%, and TNR is on par compared with the distance transformation method. Especially in the small bifurcation identification, TPR of the proposed method is 64.71% higher than the distance transformation method with a bifurcation area ratio less than 0.2.


Assuntos
Doença da Artéria Coronariana , Tomografia de Coerência Óptica , Vasos Coronários/diagnóstico por imagem , Humanos , Valor Preditivo dos Testes , Stents , Tomografia de Coerência Óptica/métodos
2.
Opt Express ; 30(7): 11130-11149, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35473063

RESUMO

In catheter based polarization sensitive optical coherence tomography (PS-OCT), a optical fiber with a rapid rotation in the catheter can cause low signal-to-noise ratio (SNR), polarization state instability, phase change of PS-OCT signals and then heavy noise-induced depolarization, which has a strong impact on the phase retardation measurement of the sample. In this paper, we analyze the noise-induced depolarization and find that the effect of depolarization can be reduced by polar decomposition after incoherent averaging in the Mueller matrix averaging (MMA) method. Namely, MMA can reduce impact of noise on phase retardation mapping. We present a Monte Carlo method based on PS-OCT to numerically describe noise-induced depolarization effect and contrast phase retardation imaging results by MMA and Jones matrix averaging (JMA) methods. The peak signal to noise ratio (PSNR) of simulated images processed by MMA is higher than about 8.9 dB than that processed by JMA. We also implement experiments of multiple biological tissues using the catheter based PS-OCT system. From the simulation and experimental results, we find the polarization contrasts processed by the MMA are better than those by JMA, especially at areas with high depolarization, because the MMA can reduce effect of noise-induced depolarization on the phase retardation measurement.


Assuntos
Refração Ocular , Tomografia de Coerência Óptica , Catéteres , Tomografia de Coerência Óptica/métodos
3.
Sensors (Basel) ; 22(15)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35957254

RESUMO

In this study, an indoor positioning shift correction architecture was developed with an improved adaptive Kalman filter (IAKF) algorithm for the people interference condition. Indoor positioning systems (IPSs) use ultra-wideband (UWB) communication technology. Triangulation positioning algorithms are generally employed for determining the position of a target. However, environmental communication factors and different network topologies produce localization drift errors in IPSs. Therefore, the drift error of real-time positioning points under various environmental factors and the correction of the localization drift error are discussed. For localization drift error, four algorithms were simulated and analyzed: movement average (MA), least square (LS), Kalman filter (KF), and IAKF. Finally, the IAKF algorithm was implemented and verified on the UWB indoor positioning system. The measurement results showed that the drift errors improved by 60% and 74.15% in environments with and without surrounding crowds, respectively. Thus, the coordinates of real-time positioning points are closer to those of actual targets.


Assuntos
Algoritmos , Movimento , Humanos , Análise dos Mínimos Quadrados
4.
Molecules ; 27(17)2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36080128

RESUMO

Morus alba L. is used in traditional Chinese medicine for its anti-diabetic activity; however, the part of the hypoglycemic activity and related active metabolites are still not fully clarified. In this study, the metabolites in the M. alba roots, leaves, twigs, and fruits extracts (70% ethanol extracts) were systematically identified, and their hypoglycemic activity was evaluated by the high-fat diet/streptozotocin-induced 2 diabetes mellitus (T2D) mouse model. A total of 60 high-level compounds, including 16 polyphenols, 43 flavonoids, and one quinic acid, were identified by high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS) combined with the fragmentation pathways of standards and the self-established database. Among them, 23 metabolites were reported for the first time from this plant. In contrast to the extracts of M. alba leaves and fruits, the extracts of roots and twigs displayed significant hypoglycemic activity The glycemia was significantly reduced from 32.08 ± 1.27 to 20.88 ± 1.82 mmol/L and from 33.32 ± 1.98 to 24.74 ± 1.02 mmol/L, respectively, after 4 weeks of treatment with roots and twigs extracts. Compound 46 (morusin), which is a high-level component identified from the extracts of M. alba roots, also displayed significant activity in decreasing the blood glucose level of T2D mice reduced from 31.45 ± 1.23 to 23.45 ± 2.13 mmol/L. In addition, the extracts of roots and twigs displayed significant activity in reducing postprandial glycemia. This work marks the first comparison of the metabolites and hypoglycemic activity of M. alba roots, leaves, twigs, and fruits extracts, and provides a foundation for further development of M. alba extracts as anti-diabetic drugs.


Assuntos
Diabetes Mellitus Tipo 2 , Morus , Animais , Glicemia/análise , Cromatografia Líquida , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Camundongos , Morus/química , Extratos Vegetais/química , Folhas de Planta/química , Espectrometria de Massas em Tandem
5.
Andrologia ; 53(10): e14198, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34375006

RESUMO

This study aimed to verify that Xuefu Zhuyu decoction (XFZYD) can improve asthenozoospermia caused by asthma, and explore its potential mechanism. Ovalbumin solution is used to induce asthma rat models. Sperm concentration and motility are used to evaluate semen quality. Immunohistochemistry (IHC), Western blotting and real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) are used to detect proteins and mRNA related to rat testis tissue. Haematoxylin and eosin (H&E) staining was used to observe changes in testicular tissues. Through network pharmacology, eriodictyol, 18-ß-glycyrrhetinic acid, naringenin, chrysin and Hispidulin were prominent active ingredients of XFZYD. We found that XFZYD regulates the expression levels of albumin (ALB), vascular endothelial growth factor A (VEGFA), interleukin 6 (IL-6) protein and mRNA, thereby improving the histopathological morphology of the testis, increasing the concentration and motility of spermatozoa. We suggest that future research can increase the detection of hormones and oxidative stress and other related indicators, so as to conduct more in-depth exploration.


Assuntos
Astenozoospermia , Asma , Medicamentos de Ervas Chinesas , Animais , Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Masculino , Ratos , Análise do Sêmen , Fator A de Crescimento do Endotélio Vascular
6.
Andrologia ; 53(7): e14085, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34091926

RESUMO

First, the bioinformatics database was used to predict the potential targets and signaling pathways of pulmonary fibrosis (PF) leading to erectile dysfunction (ED), and bleomycin sulfate was used to create a PF rat model. Then, enzyme-linked immunosorbent assay (ELISA), Western blotting, Real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect the expression of sex hormones and related proteins and mRNA, and Hematoxylin and eosin (H&E) staining was used to compare the pathological changes of penile tissue. The results showed that, compared with group A, cyclic guanosine phosphate (cGMP) content in group B decreased, protein kinase CGMP-dependent 1(PKG1) and nitric oxide synthase 3 (eNOS) protein and mRNA expression were down-regulated, and phosphodiesterase 5A (PDE5A) protein and mRNA expression was up-regulated (p < .05); the penile tissue of rats in group B had pathological damage. And there was no change in sex hormone-related indicators in the two groups (p > .05). Therefore, PF inhibits erectile function by inhibiting the cGMP-PKG pathway and reducing the expression of eNOS and PKG1 protein and mRNA. And by up-regulating the expression of PDE5A to impair erectile function.


Assuntos
Disfunção Erétil , Fibrose Pulmonar , Animais , Biologia Computacional , Humanos , Masculino , Óxido Nítrico Sintase Tipo III , Ereção Peniana , Pênis , Ratos , Ratos Sprague-Dawley
7.
Nucleic Acids Res ; 44(D1): D435-46, 2016 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-26578568

RESUMO

Owing to the importance of the post-translational modifications (PTMs) of proteins in regulating biological processes, the dbPTM (http://dbPTM.mbc.nctu.edu.tw/) was developed as a comprehensive database of experimentally verified PTMs from several databases with annotations of potential PTMs for all UniProtKB protein entries. For this 10th anniversary of dbPTM, the updated resource provides not only a comprehensive dataset of experimentally verified PTMs, supported by the literature, but also an integrative interface for accessing all available databases and tools that are associated with PTM analysis. As well as collecting experimental PTM data from 14 public databases, this update manually curates over 12 000 modified peptides, including the emerging S-nitrosylation, S-glutathionylation and succinylation, from approximately 500 research articles, which were retrieved by text mining. As the number of available PTM prediction methods increases, this work compiles a non-homologous benchmark dataset to evaluate the predictive power of online PTM prediction tools. An increasing interest in the structural investigation of PTM substrate sites motivated the mapping of all experimental PTM peptides to protein entries of Protein Data Bank (PDB) based on database identifier and sequence identity, which enables users to examine spatially neighboring amino acids, solvent-accessible surface area and side-chain orientations for PTM substrate sites on tertiary structures. Since drug binding in PDB is annotated, this update identified over 1100 PTM sites that are associated with drug binding. The update also integrates metabolic pathways and protein-protein interactions to support the PTM network analysis for a group of proteins. Finally, the web interface is redesigned and enhanced to facilitate access to this resource.


Assuntos
Bases de Dados de Proteínas , Processamento de Proteína Pós-Traducional , Sítios de Ligação , Doença , Glicosilação , Redes e Vias Metabólicas , Preparações Farmacêuticas/química , Conformação Proteica , Mapeamento de Interação de Proteínas
8.
J Am Chem Soc ; 137(5): 1746-9, 2015 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-25629796

RESUMO

MnCoGe-based compounds undergo a giant negative thermal expansion (NTE) during the martensitic structural transition from Ni2In-type hexagonal to TiNiSi-type orthorhombic structure. High-resolution neutron diffraction experiments revealed that the expansion of unit cell volume can be as large as ΔV/V ∼ 3.9%. The optimized compositions with concurrent magnetic and structural transitions have been studied for magnetocaloric effect. However, these materials have not been considered as NTE materials partially due to the limited temperature window of phase transition. The as-prepared MnCoGe-based compounds are quite brittle and naturally collapse into powders. By using a few percents (3-4%) of epoxy to bond the powders, we introduced residual stress in the bonded samples and thus realized the broadening of structural transition by utilizing the specific characteristics of lattice softening enforced by the stress. As a result, giant NTE (not only the linear NTE coefficient α but also the operation-temperature window) has been achieved. For example, the average α̅ as much as -51.5 × 10(-6)/K with an operating temperature window as wide as 210 K from 122 to 332 K has been observed in a bonded MnCo0.98Cr0.02Ge compound. Moreover, in the region between 250 and 305 K near room temperature, the α value (-119 × 10(-6)/K) remains nearly independent of temperature. Such an excellent performance exceeds that of most other materials reported previously, suggesting it can potentially be used as a NTE material, particularly for compensating the materials with large positive thermal expansions.

9.
J Orthop Surg Res ; 19(1): 393, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970109

RESUMO

BACKGROUND: To aim of this study is to assess the mechanism through which Desertliving Cistanche modulates the PI3K/AKT signaling pathway in the treatment of hyperlipidemic osteoporosis in ovariectomized rats. METHODS: We randomly assigned specific-pathogen-free (SPF) rats into five groups (n = 10 per group). The normal control group received a standard diet, while the model group, atorvastatin group, diethylstilbestrol group, and treatment group were fed a high-fat diet. Four weeks later, bilateral ovariectomies were conducted, followed by drug interventions. After six weeks of treatment, relevant indicators were compared and analyzed. RESULTS: Compared to the normal control group, rats in the model group exhibited blurred trabecular morphology, disorganized osteocytes, significantly elevated levels of bone-specific alkaline phosphatase (BALP), bone Gla-protein (BGP), total cholesterol (TC), tumor necrosis factor-α (TNF-α), and receptor activator of NF-κB ligand (RANKL). Also, the model group revealed significantly reduced levels of ultimate load, fracture load, estradiol (E2), bone mineral density (BMD), osteoprotegerin (OPG), and phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) in femoral tissue. The atorvastatin group presented with higher TC and TNF-α levels compared to the normal control group. Conversely, the treatment group demonstrated enhanced trabecular morphology, denser structure, smaller bone marrow cavities, and reduced BALP, BGP, TC, TNF-α, and RANKL levels. Furthermore, the treatment group exhibited higher levels of E2, BMD, OPG, and PI3K and Akt in bone tissue compared to the model group. The treatment group also had lower TC and TNF-α levels than the atorvastatin group. Biomechanical analysis indicated that after administration of Desertliving Cistanche, the treatment group had reduced body mass, increased ultimate and fracture load of the femur, denser bone structure, smaller bone marrow cavities, and altered periosteal arrangement compared to the model group. CONCLUSION: Our study revealed that Desertliving Cistanche demonstrated significant efficacy in preventing and treating postmenopausal hyperlipidemic osteoporosis in rats.


Assuntos
Cistanche , Hiperlipidemias , Osteoporose , Ovariectomia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Animais , Ovariectomia/efeitos adversos , Feminino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Hiperlipidemias/complicações , Hiperlipidemias/metabolismo , Osteoporose/etiologia , Osteoporose/metabolismo , Ratos , Ratos Sprague-Dawley , Densidade Óssea/efeitos dos fármacos , Distribuição Aleatória
10.
Phys Med Biol ; 69(15)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38981596

RESUMO

Objective. Bifurcation detection in intravascular optical coherence tomography (IVOCT) images plays a significant role in guiding optimal revascularization strategies for percutaneous coronary intervention (PCI). We propose a bifurcation detection method using vision transformer (ViT) based deep learning in IVOCT.Approach. Instead of relying on lumen segmentation, the proposed method identifies the bifurcation image using a ViT-based classification model and then estimate bifurcation ostium points by a ViT-based landmark detection model.Main results. By processing 8640 clinical images, the Accuracy and F1-score of bifurcation identification by the proposed ViT-based model are 2.54% and 16.08% higher than that of traditional non-deep learning methods, are similar to the best performance of convolutional neural networks (CNNs) based methods, respectively. The ostium distance error of the ViT-based model is 0.305 mm, which is reduced 68.5% compared with the traditional non-deep learning method and reduced 24.81% compared with the best performance of CNNs based methods. The results also show that the proposed ViT-based method achieves the highest success detection rate are 11.3% and 29.2% higher than the non-deep learning method, and 4.6% and 2.5% higher than the best performance of CNNs based methods when the distance section is 0.1 and 0.2 mm, respectively.Significance. The proposed ViT-based method enhances the performance of bifurcation detection of IVOCT images, which maintains a high correlation and consistency between the automatic detection results and the expert manual results. It is of great significance in guiding the selection of PCI treatment strategies.


Assuntos
Aprendizado Profundo , Processamento de Imagem Assistida por Computador , Tomografia de Coerência Óptica , Tomografia de Coerência Óptica/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Vasos Coronários/diagnóstico por imagem
11.
ACS Appl Mater Interfaces ; 16(38): 51229-51240, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39285684

RESUMO

The recent past has witnessed remarkable progress in organic electronics, driven by the quest for flexible, lightweight, and cost-effective electronic devices. Semiconducting polymers (SCPs) have emerged as key materials in this field, offering unique electronic and optoelectronic properties along with mechanical flexibility. This study focuses on designing, synthesizing, and utilizing novel donor-acceptor (D-A) copolymer-based SCPs introducing a difluorothiophene moiety in the polymeric backbone. The importance of fluorine substitution for backbone planarity was verified by density functional theory calculations, comparing it with a nonfluorine substituted counterpart. Through the Unidirectional Floating Film Transfer Method (UFTM), we fabricated highly oriented thin films, resulting in increased optical anisotropy with dichroic ratios reaching 19.3 in PC20-FT thin films, one of the highest optical anisotropy observed for solution processable SCP thin films. X-ray diffraction and atomic force microscopy results validated the increase in the crystallinity and domain size with the increasing alkyl chain length. Finally, we elucidate these findings in the context of electrical applications by fabricating organic field-effect transistors revealing anisotropic charge transport achieving a promising mobility of 1.24 cm2V-1s-1 and mobility anisotropy of 39.5. This study offers insights into the design principles and performance optimization of SCP-based devices, paving the way for advancements in plastic electronics.

13.
J Pharm Anal ; 13(11): 1296-1308, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38174116

RESUMO

Ginsenoside Rg5 is a rare ginsenoside showing promising tumor-suppressive effects. This study aimed to explore its radio-sensitizing effects and the underlying mechanisms. Human lung adenocarcinoma cell lines A549 and Calu-3 were used for in vitro and in vivo analysis. Bioinformatic molecular docking prediction and following validation by surface plasmon resonance (SPR) technology, cellular thermal shift assay (CETSA), and isothermal titration calorimetry (ITC) were conducted to explore the binding between ginsenoside Rg5 and 90 kD heat shock protein alpha (HSP90α). The effects of ginsenoside Rg5 on HSP90-cell division cycle 37 (CDC37) interaction, the client protein stability, and the downstream regulations were further explored. Results showed that ginsenoside Rg5 could induce cell-cycle arrest at the G1 phase and enhance irradiation-induced cell apoptosis. It could bind to HSP90α with a high affinity, but the affinity was drastically decreased by HSP90α Y61A mutation. Co-immunoprecipitation (Co-IP) and ITC assays confirmed that ginsenoside Rg5 disrupts the HSP90-CDC37 interaction in a dose-dependent manner. It reduced irradiation-induced upregulation of the HSP90-CDC37 client proteins, including SRC, CDK4, RAF1, and ULK1 in A549 cell-derived xenograft (CDX) tumors. Ginsenoside Rg5 or MRT67307 (an IKKε/TBK1 inhibitor) pretreatment suppressed irradiation-induced elevation of the LC3-II/ß ratio and restored irradiation-induced downregulation of p62 expression. In A549 CDX tumors, ginsenoside Rg5 treatment suppressed LC3 expression and enhanced irradiation-induced DNA damage. In conclusion, ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma. It interacts with HSP90α and reduces the binding between HSP90 and CDC37, thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.

14.
Phys Med Biol ; 69(1)2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38035376

RESUMO

Objective.Intravascular optical coherence tomography is a useful tool to assess stent adherence and dilation, thus guiding percutaneous coronary intervention and minimizing the risk of surgery. However, each pull-back OCT images may contain thousands of stent struts, which are tiny and dense, making manual stent labeling slow and costly for medical resources.Approach. This paper proposed a multiple attention convolutional model for automatic stent struts detection of OCT images. Multiple attention mechanisms were utilized to strengthen the feature extraction and feature fusion capabilities. In addition, to precisely detect tiny stent struts, the model integrated multiple anchor frames to predict targets in the output.Main results. The model was trained in 4625 frames OCT images of 37 patients and tested in 1156 frames OCT images of 9 patients, and achieved a precision of 0.9790 and a recall of 0.9541, which were significantly better than mainstream convolutional models. In terms of detection speed, the model achieved 25.2 ms per image. OCT images from different collection systems, collection times, and challenging scenarios were experimentally tested, and the model demonstrated stable robustness, achieving precision and recall higher than 0.9630. Meanwhile, clear 3D construction of the stent was achieved.Significance. In conclusion, the proposed model solves the problems of slow manual analysis and occupying a large amount of medical manpower resources. It enhances the detection efficiency of tiny and dense stent struts, thus facilitating the application of OCT quantitative analysis in real clinical scenarios.


Assuntos
Intervenção Coronária Percutânea , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Stents , Vasos Coronários , Resultado do Tratamento
15.
Front Nutr ; 10: 1113875, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36969820

RESUMO

Objectives: It remains controversial whether sarcopenia has any significant impact on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) or immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). Therefore, in this study, we aimed to assess the association between sarcopenia and clinical outcomes in patients with advanced NSCLC receiving EGFR-TKIs or ICIs as a first-line therapy. Methods: We retrospectively enrolled 131 patients with advanced NSCLC treated with first-line EGFR-TKIs or ICIs between 1 March 2019 and 31 March 2021. To estimate sarcopenia, we calculated skeletal muscle index (SMI) as the ratio of skeletal muscle area (cm2) to height squared (m2). Associations between sarcopenia and overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and log-rank tests, respectively. A Cox proportional hazards regression model was used to assess the factors associated with OS and PFS. The Student's t-test or Mann-Whitney U test was used to compare the SMI between patients with or without objective response and disease control. The chi-squared test was used to compare adverse events (AEs) between patients with and without sarcopenia. Results: Among the 131 patients, 35 (26.7%) were diagnosed with sarcopenia. Sarcopenia was an independent predictor of poor OS and PFS (p < 0.05) overall and in the EGFR-TKI- and ICI-treated cohorts. Among all patients, those with sarcopenia showed significantly shorter OS and PFS than those without sarcopenia (median OS and PFS: 13.0 vs. 26.0 months and 6.4 vs. 15.1 months; both p < 0.001). These associations were consistent across the subtypes of most clinical characteristics. Statistically significant differences between the objective response (OR) and non-OR groups were also observed in the mean SMI (OR group, 43.89 ± 7.55 vs. non-OR group, 38.84 ± 7.11 cm2/m2; p < 0.001). In addition, we observed similar results with disease control (DC) and non-DC groups (DC group, 42.46 ± 7.64 vs. non-DCR group, 33.74 ± 4.31 cm2/m2; p < 0.001). The AEs did not differ significantly between the sarcopenia and non-sarcopenia groups. Conclusion: Sarcopenia before treatment might be a significant predictor of poor clinical outcomes (shorter OS and PFS, fewer ORs, less DC) in patients with advanced NSCLC treated with EGFR-TKIs or ICIs as the first-line therapy.

16.
FEBS J ; 290(14): 3664-3687, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36906928

RESUMO

Ferroptosis, featuring an iron-dependent peroxidation of lipids, is a novel form of programmed cell death that may hold great potential in cancer therapy. Our study found that palmitic acid (PA) inhibited colon cancer cell viability in vitro and in vivo, in conjunction with an accumulation of reactive oxygen species and lipid peroxidation. The ferroptosis inhibitor Ferrostatin-1 but not Z-VAD-FMK (a pan-caspase inhibitor), Necrostatin-1 (a potent necroptosis inhibitor), or CQ (a potent inhibitor of autophagy), rescued the cell death phenotype induced by PA. Subsequently, we verified that PA induces ferroptotic cell death through excess iron as cell death was inhibited by iron chelator deferiprone (DFP), while it was exacerbated by a supplement of ferric ammonium citrate. Mechanistically, PA affects intracellular iron content by inducing endoplasmic reticulum (ER) stress leading to ER calcium release and regulating transferrin (TF) transport through increasing cytosolic calcium levels. Furthermore, we observed that cells with high expression of CD36 were more vulnerable to PA-induced ferroptosis. Altogether, our findings reveal that PA engages in anti-cancer properties by activating ER stress/ER calcium release/TF-dependent ferroptosis, and PA might serve as a compound to activate ferroptosis in colon cancer cells with high CD36 expression.


Assuntos
Neoplasias do Colo , Ferroptose , Humanos , Ferro/metabolismo , Cálcio , Ácido Palmítico/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética
17.
Front Nutr ; 9: 1050643, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36532533

RESUMO

Objectives: Although lipids have been assessed for their possible roles in cancer survival prediction, studies on the association between serum triglyceride (TG) levels and the prognosis of esophageal squamous cell carcinoma (ESCC) patients are limited. This study aimed to evaluate whether serum TG is associated with outcomes in patients with ESCC and investigate any interaction between serum TG and clinical parameters, especially body fat mass. Materials and methods: We conducted a prospective case study on patients diagnosed with ESCC between March 2012 and November 2018. We measured patients' serum TG levels before and after treatment. The association between serum TG and overall survival (OS) was evaluated using hazard ratios. We sought to determine a threshold point using optimal stratification. Survival analysis was performed using Kaplan-Meier curves and a Cox proportional hazards model. Results: Of the 257 participants diagnosed with ESCC, 200 (77.8%) were men. Median follow-up time was 22.4 months (range 3.3-92.4 months). Using univariate Cox proportional hazard analysis and subsequent multivariate analysis, post-TG levels, Karnofsky performance scores, T stages, and chemotherapy cycles were shown to be independent prognostic factors for OS (p < 0.05). The post-TG cut-off point to best classify patients with respect to time to mortality was 1.47 mmol/L. A post-TG level of ≥ 1.47 mmol/L could independently predict a better OS (hazard ratio: 0.55, 95% confidence interval: 0.37-0.79). The associations were consistent across the subtypes of clinical parameters. Furthermore, the post-body mass index, post-subcutaneous adipose tissue area, post-visceral adipose tissue area, post-total adiposity tissue area, and post-total adipose density exhibited a strong positive association with post-TG levels. Conclusion: Post-TG levels were found to be a significant positive prognostic biomarker for body fat mass and OS in ESCC patients.

18.
Adv Sci (Weinh) ; 9(29): e2201992, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36031388

RESUMO

Although targeting cancer metabolism is a promising therapeutic strategy, clinical success depends on accurate molecular and metabolic subtyping. Here, this study reports two metabolism-based molecular subtypes associated with the ketogenic treatment of colon cancer: glycolytic (glycolysis+ /ketolysis- ) and ketolytic (glycolysis+ /ketolysis+ ), which are manifested by distinct profiles of metabolic enzymes and mitochondrial dysfunction, and by different responses to ketone-containing interventions in vitro and in vivo. Notably, the glycolytic subtype is able to be transformed into the ketolytic subtype in p53-mutated tumors upon glucose limitation, rendering resistance to ketogenic therapy associated with upregulation of ketolytic enzymes, such as OXCT1 by mutant p53. The allosteric activator of mutant p53 effectively blocks the rewired molecular expression and the reprogrammed metabolism, leading to the suppression of tumor growth. The findings highlight the utility of metabolic subtyping to guide ketogenic therapy in colon cancer and identify mutant p53 as a synthetic lethality target for ketogenic treatment.


Assuntos
Neoplasias do Colo , Proteína Supressora de Tumor p53 , Neoplasias do Colo/genética , Neoplasias do Colo/terapia , Glucose/metabolismo , Humanos , Corpos Cetônicos , Cetonas , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
19.
J Biophotonics ; 14(3): e202000370, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33247508

RESUMO

We present a three-dimensional (3D) spatial reconstruction of coronary arteries based on fusion of intravascular optical coherence tomography (IVOCT) and digital subtraction angiography (DSA). Centerline of vessel in DSA images is exacted by multi-scale filtering, adaptive segmentation, morphology thinning and Dijkstra's shortest path algorithm. We apply the cross-correction between lumen shapes of IVOCT and DSA images and match their stenosis positions to realize co-registration. By matching the location and tangent direction of the vessel centerline of DSA images and segmented lumen coordinates of IVOCT along pullback path, 3D spatial models of vessel lumen are reconstructed. Using 1121 distinct positions selected from eight vessels, the correlation coefficient between 3D IVOCT model and DSA image in measuring lumen radius is 0.94% and 97.7% of the positions fall within the limit of agreement by Bland-Altman analysis, which means that the 3D spatial reconstruction IVOCT models and DSA images have high matching level.


Assuntos
Vasos Coronários , Tomografia de Coerência Óptica , Algoritmos , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Imageamento Tridimensional
20.
J Biophotonics ; 14(10): e202100124, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34185435

RESUMO

We present an automatic lumen segmentation method using uniqueness of connected region for intravascular optical coherence tomography (IVOCT), which can effectively remove the effect on lumen segmentation caused by blood artifacts. Utilizing the uniqueness of vascular wall on A-lines, we detect the A-lines shared by multiple connected regions, identify connected regions generated by blood artifacts using traversal comparison of connected regions' location, shared ratio and area ratio and then remove all artifacts. We compare these three methods by 216 challenging images with severe blood artifacts selected from clinical 1076 IVOCT images. The metrics of the proposed method are evaluated including Dice index, Jaccard index and accuracy of 94.57%, 90.12%, 98.02%. Compared with automatic lumen segmentation based on the previous morphological feature method and widely used dynamic programming method, the metrics of the proposed method are significantly enhanced, especially in challenging images with severe blood artifacts.


Assuntos
Algoritmos , Tomografia de Coerência Óptica , Artefatos
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