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1.
Anal Chem ; 93(46): 15373-15380, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34748327

RESUMO

The improvement of on-tissue chemical derivatization for mass spectrometry imaging (MSI) of low-abundance and/or poorly ionizable functional molecules in biological tissue without delocalization is challenging. Here, we developed a novel hydrogel-assisted chemical derivatization (HCD) approach coupled with airflow-assisted desorption electrospray ionization (AFADESI)-MSI, allowing for enhanced visualization of inaccessible molecules in biological tissues. The derivatization reagent Girard's P (GP) reagent was creatively packaged into a hydrogel to form HCD blocks that have reactivity to carbonyl compounds as well as the feasibility of "cover/uncover" contact mode with tissue sections. The HCD blocks provided a favorable liquid microenvironment for the derivatization reaction and reduced matrix effects from derivatization reagents and tissue without obvious molecular migration, thus improving the derivatization efficiency. With this methodology, unusual carbonyl metabolites, including 166 fatty aldehydes (FALs) and 100 oxo fatty acids (FAs), were detected and visualized in rat brain, kidney, and liver tissue. This study provides a new approach to enhance chemical labeling for in situ tissue submetabolome profiling and improves our knowledge of the molecular histology and complex metabolism of biological tissues.

2.
Biomed Res Int ; 2021: 5522452, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34820455

RESUMO

Objectives: To evaluate the utility of radiomics features in differentiating central lung cancers and atelectasis on contrast-enhanced computed tomography (CT) images. This study is retrospective. Materials and Methods: In this study, 36 patients with central pulmonary cancer and atelectasis between July 2013 and June 2018 were identified. A total of 1,653 2D and 2,327 3D radiomics features were extracted from segmented lung cancers and atelectasis on contrast-enhanced CT. The refined features were investigated for usefulness in classifying lung cancer and atelectasis according to the information gain, and 10 models were trained based on these features. The classification model is trained and tested at the region level and pixel level, respectively. Results: Among all the extracted features, 334 2D features and 1,507 3D features had an information gain (IG) greater than 0.1. The highest accuracy (AC) of the region classifiers was 0.9375. The best Dice score, Hausdorff distance, and voxel AC were 0.2076, 45.28, and 0.8675, respectively. Conclusions: Radiomics features derived from contrast-enhanced CT images can differentiate lung cancers and atelectasis at the regional and voxel levels.

3.
PLoS Negl Trop Dis ; 15(10): e0009801, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34606501

RESUMO

Nifurtimox is indicated in Chagas disease but determining its effectiveness in chronic disease is hindered by the length of time needed to demonstrate negative serological conversion. We manually reviewed long-term follow-up data from hospital records of patients with chronic Chagas disease (N = 1,497) in Argentina diagnosed during 1967-1980. All patients were aged ≥18 years at diagnosis and were either treated with nifurtimox (n = 968) or received no antitrypanosomal treatment (n = 529). The primary endpoint was negative seroconversion (the "event"), defined as a change from positive to negative in the serological or parasitological laboratory test used at diagnosis. Time to event was from baseline visit to date of endpoint event or censoring. The effectiveness of nifurtimox versus no treatment was estimated with Cox proportional hazard regression using propensity scores with overlap weights to calculate the hazard ratio and 95% confidence interval. The nifurtimox group was younger than the untreated group (mean, 32.4 vs. 40.3 years), with proportionally fewer females (47.9% vs. 60.1%), and proportionally more of the nifurtimox group than the untreated group had clinical signs and symptoms of Chagas disease at diagnosis (28.9% vs. 14.0%). Median maximum daily dose of nifurtimox was 8.0 mg/kg/day (interquartile range [IQR]: 8.0-9.0) and median treatment duration was 44 days (IQR: 1-90). Median time to event was 2.1 years (IQR: 1.0-4.5) for nifurtimox-treated and 2.4 years (IQR: 1.0-4.2) for untreated patients. Accounting for potential confounders, the estimated hazard ratio (95% confidence interval) for negative seroconversion was 2.22 (1.61-3.07) favoring nifurtimox. Variable treatment regimens and follow-up duration, and an uncommonly high rate of spontaneous negative seroconversion, complicate interpretation of this epidemiological study, but with the longest follow-up and largest cohort analyzed to date it lends weight to the benefit of nifurtimox in adults with chronic Chagas disease. Trial registration: The study protocol was registered at ClinicalTrials.gov: NCT03784391.

4.
J Mater Chem B ; 9(44): 9116-9122, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34617547

RESUMO

Featuring simultaneous multicolor imaging for multiple targets, a synergistic strategy has become promising for fluorescence imaging applications. Visible and first near infrared (NIR-I, 700-900 nm) fluorophores have been explored for multicolor imaging to achieve good multi-target capacity, but they are largely hampered by the narrow imaging bands available (400-900 nm, bandwidth 500 nm), the broad emission spectra of many fluorophores, shallow tissue penetration and scattering loss. With attractive characteristic emission peaks in the second NIR window (NIR-II, 1000-1700 nm), a narrow emission spectrum, and deeper tissue penetration capability, rare-earth doped nanoparticles (RENPs) have been considered by us to be outstanding candidates for multicolor bioimaging. Herein, two RENPs, NaYF4:Yb20Er2@NaYF4 and NaYF4:Nd5@NaYF4, were prepared and modified with polyethylene glycol (PEG) to explore simultaneous imaging in the NIR-IIb (1530 nm, under 980 nm laser excitation) and the NIR-II (1060 nm, under 808 nm laser excitation) windows. The PEGylated-RENPs (RENPs@PEG) were able to simultaneously visualize the circulatory system, trace the lymphatic system, and evaluate the skeletal system. Our study demonstrates that RENPs have high synergistic imaging capability in multifunctional biomedical applications using their NIR-II fluorescence. Importantly, the two RENPs@PEG are complementary to each other for higher temporal resolution in NaYF4:Nd5@NaYF4@PEG and higher spatial resolution in NaYF4:Yb20Er2@NaYF4@PEG, which may provide more comprehensive and accurate imaging diagnosis. In conclusion, RENPs are highly promising nanomaterials for multicolor imaging in the NIR-II window.

5.
J Mater Chem B ; 9(36): 7447-7460, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34551057

RESUMO

Nowadays, cancer is one of the most serious diseases threatening the health of human beings, and imaging-guided photothermal therapy (PTT) is rapidly emerging as a potent oncotherapy strategy due to its unique advantages of high efficiency, noninvasiveness, visualization, and accuracy. In this study, a multifunctional nanoplatform based on gadolinium ion chelated natural anthocyanins (ACNs) is reported, which can be used not only as an excellent photoacoustic/magnetic resonance (PA/MR) dual-modal contrast agent but also for imaging-guided tumor PTT. The nanoparticles obtained have a suitable size, good dispersity, and physiological stability. The excellent biocompatibility and remarkable photothermal effect of the nanoparticles in vitro were demonstrated by CCK-8 assays and co-staining experiments. Moreover, the magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) results obtained in vivo showed that the nanoparticles were ideal dual-modal contrast agents whether given by intravenous or intratumoral injection. After intratumoral injection, the dual-modal PAI/MRI was used for determining the maximum diffusion time of the probe in the tumor site to guide laser treatment, achieving complete tumor elimination without normal tissue injury. Importantly, ACN is a natural compound extracted from black carrots, possessing native biocompatibility and biodegradability, which was further proved by the results of the detailed safety evaluation. Overall, the as-prepared nanoparticles displayed significant tumor diagnosis and treatment effects while mitigating biosafety concerns, and thus this was found to be a promising nanotherapeutic method for cancer treatment.

6.
Talanta ; 235: 122804, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34517662

RESUMO

Identifying the writing sequence of seals and signatures in documents is often performed and difficult to resolve in forensic determination. Morphological and physical-chemical analysis methods are often limited by the destructive nature of samples, a high signal response strength and specific materials. Mass spectrometry imaging (MSI) has been used as an alternative method because it can generate molecular images from many surfaces and produce rich chemical information. Herein, we developed a sequence identification method by coupling an air flow-assisted desorption electrospray ionization (AFADESI)-MSI system with a chemometric analysis, which can holistically and directly analyse document samples under ambient, moderate and selectable conditions and maintain the original appearance of the paper documents after sampling. By integrating principal component analysis (PCA) and the partial least squares discriminant analysis (PLS-DA), equivocal point analysis can be objectively performed, where knowing the components of the seal or signature is not necessary to identify the sequence. In total, 28 prepared samples with known sequences and two original blind test samples were analysed. One prepared sample was analysed in negative ionization mode, and other samples were inferred in positive ionization mode. All writing sequences were in accordance with the actual case. The writing sequence of the blind testing of the original samples was correctly identified. This study provided a convenient, objective and quasi-nondestructive method to investigate the sequence differences among equivocal document samples and is promising for providing an alternative method for the sequence identification of seals and signatures in questionable documents.


Assuntos
Espectrometria de Massas por Ionização por Electrospray , Redação , Análise Discriminante , Análise dos Mínimos Quadrados , Espectrometria de Massas , Análise de Componente Principal
7.
Front Oncol ; 11: 648187, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490078

RESUMO

Fibroblast activation protein-α (FAP) is a type II integral serine protease that is specifically expressed by activated fibroblasts. Cancer-associated fibroblasts (CAFs) in the tumor stroma have an abundant and stable expression of FAP, which plays an important role in promoting tumor growth, invasion, metastasis, and immunosuppression. For example, in females with a high incidence of breast cancer, CAFs account for 50-70% of the cells in the tumor's microenvironment. CAF overexpression of FAP promotes tumor development and metastasis by influencing extracellular matrix remodeling, intracellular signaling, angiogenesis, epithelial-to-mesenchymal transition, and immunosuppression. This review discusses the basic biological characteristics of FAP and its applications in the diagnosis and treatment of various cancers. We review the emerging basic and clinical research data regarding the use of nanomaterials that target FAP.

8.
Small ; 17(41): e2103252, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34499414

RESUMO

In the second near-infrared (NIR-II) biowindow, multimodal optical imaging-guided precise antitumor therapy is a novel strategy for high-efficiency tumor theranostics, however, the all-in-one dual NIR-II photoacoustic (NIR-II PA) and NIR-II fluorescence (NIR-II FL) nanoprobes have been rarely reported mainly due to the short of a simple and universal design approach. Herein, a NIR-II PA/NIR-II FL imaging-adjustable nanozyme (HSC-2) is designed and developed to guide precise photothermal-catalytic synergistic therapy. Based on the ionic liquids adsorption capacity, the electronic structure of zeolite nano-Beta (three dimensional 12-ring pore system and large surface area) can be turned from the indirect band gap to direct band gap via doping carbon in the framework, resulting in outstanding NIR-II FL emission characteristics. As the silicon etching reaction proceeds, HSC-2 shows superior dual-modal NIR-II PA/NIR-II FL imaging performance facilitated by the optimal silicon-to-carbon ratio, simultaneously ensuring efficient tumor photothermal therapy (PTT) in the NIR-II window. Impressively, the peroxidase-mimic activity of HSC-2 in the tumor microenvironment could be further remarkably enhanced by its photothermal effect, leading to excellent synergistic PTT/catalytic therapy. Moreover, the HSC-2 exhibits dual-enzyme activity, and its catalase-like property could effectively eliminate excessive ROS for protection of the normal cells.


Assuntos
Neoplasias , Técnicas Fotoacústicas , Zeolitas , Carbono , Linhagem Celular Tumoral , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Imagem Óptica , Fototerapia , Nanomedicina Teranóstica , Microambiente Tumoral
9.
J Mol Histol ; 52(5): 1067-1080, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34398360

RESUMO

Lipid metabolism is closely related to the improvement of vascular calcification (VC) in chronic kidney disease (CKD). Globular adiponectin (gAd) has been reported to be involved in the development of VC in CKD, but the detailed regulatory role remains unclear. The present study is aimed to investigate the biological function and the underlying regulation mechanism of gAd in the process of VC during CKD. Vascular smooth muscle cells (VSMCs) calcification was determined by Alizarin Red S staining. Protein signaling related with VC was tested by western blotting. The expression and intracellular localization of runt-related transcription factor 2 (Runx2) was detected by immunofluorescence and uraemic rat with VC was established by a two-step nephrectomy. Combined with the results of Alizarin Red S staining, we discovered that ß-glycerophosphate (ß-Gp)-induced the osteoblastic differentiation of VSMCs was significantly reversed by gAd treatment. Along with the VSMCs calcification and the increase of Runx2 in ß-Gp-exposed VSMCs, the activities of protein kinase B (AKT) and Wnt/ß-catenin pathway were enhanced, but that were counteracted by the exposure of gAd in rat and human VSMCs. After administration with agonists of the Wnt (SKL2001) and AKT (SC79), there appeared more osteoblastic differentiation and higher expression of Runx2 in gAd-treated VSMCs, but showing lower impact in the presence of SC79 than that in the presence of SKL2001. In the in vivo experiments, intravenous injection of gAd also significantly inhibited VC and Runx2 level in uraemic rat in a dose-dependent manner, possibly through regulating Wnt/ß-catenin pathway. This study demonstrates that gAd ameliorates osteoblastic differentiation of VSMCs possibly by blocking PI3K/AKT and Wnt/ß-catenin signaling transduction. The findings provide an important foundation for gAd in treating VC in kidney diseases.

10.
J Affect Disord ; 293: 415-421, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34246950

RESUMO

BACKGROUND: Owing to the widespread use of smartphones, researchers have an increasing interest in smartphone addiction. The purpose of this study is to look into the outcomes of smartphone addiction while answering when and how smartphone addiction may predict university students' depression and anxiety. METHODS: Primary data were collected from 355 students studying in different universities in China. Participants completed Smartphone Addiction Scale-Short Version (SAS-SV), Bedtime Procrastination Scale (BPS), Self-control Scale (SCS) and Depression-Anxiety-Stress Scale (DASS). PROCESS macros in SPSS24.0 were used to examine the moderated mediating effects. RESULTS: Smartphone addiction Scale scores were positively correlated with depression, anxiety among university students through bedtime procrastination. Self-control was found to play the moderating role such that the mediated relationships were weak for students with high self-control. LIMITATIONS: This study is a cross sectional study, so we cannot make causal inferences. CONCLUSIONS: Individuals with smartphone addiction are inclined to postpone their bedtime and further experience more depression and anxiety. Self-control serves as a protective factor for bedtime procrastination, depression and anxiety.


Assuntos
Procrastinação , Autocontrole , Ansiedade , Estudos Transversais , Depressão , Humanos , Transtorno de Adição à Internet , Smartphone
11.
Neurochem Int ; 148: 105110, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34166749

RESUMO

As a subjective mood-related disorder with an unclear mechanism, depression has many problems in its diagnosis, which offers great space and value for research. At present, the methods commonly used to judge whether an animal model of depression has been established are mainly by biochemical index detection and behavioral tests, both of which inevitably cause stress in animals. Stress-induced hair growth inhibition has been widely reported in humans and animals. The simplicity of collecting hair samples and the observable state of hair growth has significant advantages; we tried to explore whether the parameters related to hair growth could be used as auxiliary indicators to evaluate a depression model in animals. The length and weight of the hair were calculated. Correlation analysis was conducted between the depressive behavioral results and the glucocorticoid levels in hair and serum. Learned helplessness combined with chronic restraint stress, and chronic unpredictable stress in the animal were detectable by superficial observation, weight ratio, and length of hair, and follicular development scores were significantly reduced compared to the control. The hair growth parameters of rats with depression, the rise in corticosterone, and the corresponding changes in behavioral parameters were significantly correlated. The neurotrophic factors, glucocorticoid-receptor (GR), brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and fibroblast growth factor 5 (FGF5), are associated with depression and hair growth. Significant differences were detected between the stress and control groups, suggesting that the mechanism underlying the stress-phenomenon inhibition of hair growth may be related to growth factor mediation.

12.
J Colloid Interface Sci ; 603: 17-24, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34186395

RESUMO

Performance of single-atom catalysis largely depends on the interaction between the metal and the supporter. Herein, ethylene glycol (EG) was used as a molecular bridge connecting Palladium (Pd) and bismuth oxybromide (BiOBr) to form atomically dispersed Pd catalyst (Pd-EG-BiOBr) for photocatalytic nitrogen fixation under ambient conditions. Compared with 0.20 wt% Pd-BiOBr, 0.20 wt% Pd-EG-BiOBr greatly promoted the photocatalytic nitrogen fixation activity, affording an ammonia formation rate of 124.63 µmol·h-1. The molecular bridge mechanism during catalyst formation and photocatalysis is speculated based on Transmission electron microscopy, In-situ Fourier transform infrared spectra, Electron spin resonance spectra, UV-vis diffuse reflectance spectra, Photoluminescence spectra and Density Functional Theory calculations. The results show that EG not only induces the formation of atomically dispersed Pd, but also enhances the electron density of Pd and activation capacity of nitrogen molecules. This work opens a new door to applications of atomically dispersed Pd supported catalysts for high efficiency photocatalytic nitrogen fixation.

13.
Front Psychol ; 12: 651612, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122236

RESUMO

Perceived social support is positively related to life satisfaction in infertile women. Whereas, the underlying mechanism of this relationship is unclear. The present study aimed to investigate whether self-compassion mediated the relationship of perceived social support with life satisfaction and whether infertility self-efficacy moderated the relationship between perceived social support and self-compassion in infertile women. A total of 290 infertile women in mainland China undergoing treatment completed an online survey assessing perceived social support, life satisfaction, self-compassion, and infertility self-efficacy. The results supported the mediation model that perceived social support was associated with life satisfaction via self-compassion. Besides, infertility self-efficacy moderated the relationship between perceived social support and self-compassion. Specifically, perceived social support displayed a stronger predictive effect on self-compassion when infertile women had higher level of infertility self-efficacy.

14.
Oncol Lett ; 22(2): 607, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34188709

RESUMO

Tumor-derived exosomal microRNAs (miRNAs/miRs) serve a vital biological role in tumorigenesis and development, but the effects and underlying mechanisms remain unclear. To explore the impact of exosomal miR-433 in non-small cell lung cancer (NSCLC) and understand its mechanism of action in NSCLC progression, the present study isolated the exosomes from the plasma of patients with NSCLC after chemotherapy and found that miR-433 expression was lower in plasma of patients with resistant NSCLC compared with in plasma of patients with sensitive NSCLC and in normal serum. Additionally, miR-433 expression was markedly negatively associated with a large tumor size, distant metastasis, advanced TNM stage and a poor prognosis in patients with NSCLC. miR-433 inhibited tumor growth by blocking the cell cycle in vitro and in vivo, as well as by promoting apoptosis and T-cell infiltration in the tumor microenvironment. Additionally, miR-433 inhibited chemoresistance to cisplatin by regulating DNA damage. Moreover, miR-433 inactivated the WNT/ß-catenin signaling pathway by targeting transmembrane p24 trafficking protein 5 in NSCLC. Overall, the current findings may provide a potential prognostic biomarker and therapeutic target for patients with NSCLC.

15.
Anal Chem ; 93(17): 6746-6754, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33890766

RESUMO

Metabolic networks and their dysfunction in the brain are closely associated with central nervous function and many psychogenic diseases. Thus, it is of utmost importance to develop a high-throughput imaging method for metabolic network mapping. Here, we developed a metabolic network mapping method to discover the metabolic contexts and alterations with spatially resolved information from the microregion of the brain by ambient-air flow-assisted desorption electrospray ionization mass spectrometry imaging and metabolomics analysis, which can be performed without any chemical derivatization, labels, or complex sample pretreatment. This method can map hundreds of different polar functional metabolites involved in multiple metabolic pathways, including not only neurotransmitters but also purines, organic acids, polyamines, cholines, and carbohydrates, in the rat brain. These high-coverage metabolite profile and microregional distribution information constitute complex networks that regulate advanced functions in the central nervous system. Moreover, this methodology was further used to discover not only the dysregulated metabolites but also the brain microregions involved in the pathology of a scopolamine-treated Alzheimer's model. Furthermore, this methodology was demonstrated to be a powerful visualizing tool that could offer novel insight into the metabolic events and provide spatial information about these events in central nervous system diseases.


Assuntos
Metabolômica , Espectrometria de Massas por Ionização por Electrospray , Animais , Encéfalo , Redes e Vias Metabólicas , Neurotransmissores , Ratos
16.
Cell Death Dis ; 12(3): 277, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723244

RESUMO

Glioma stem cells (GSCs) contribute to therapy resistance and poor outcomes for glioma patients. A significant feature of GSCs is their ability to grow in an acidic microenvironment. However, the mechanism underlying the rewiring of their metabolism in low pH remains elusive. Here, using metabolomics and metabolic flux approaches, we cultured GSCs at pH 6.8 and pH 7.4 and found that cells cultured in low pH exhibited increased de novo purine nucleotide biosynthesis activity. The overexpression of glucose-6-phosphate dehydrogenase, encoded by G6PD or H6PD, supports the metabolic dependency of GSCs on nucleotides when cultured under acidic conditions, by enhancing the pentose phosphate pathway (PPP). The high level of reduced glutathione (GSH) under acidic conditions also causes demand for the PPP to provide NADPH. Taken together, upregulation of G6PD/H6PD in the PPP plays an important role in acidic-driven purine metabolic reprogramming and confers a predilection toward glioma progression. Our findings indicate that targeting G6PD/H6PD, which are closely related to glioma patient survival, may serve as a promising therapeutic target for improved glioblastoma therapeutics. An integrated metabolomics and metabolic flux analysis, as well as considering microenvironment and cancer stem cells, provide a precise insight into understanding cancer metabolic reprogramming.


Assuntos
Acidose/metabolismo , Neoplasias Encefálicas/metabolismo , Metabolismo Energético , Glioma/metabolismo , Células-Tronco Neoplásicas/metabolismo , Purinas/metabolismo , Acidose/genética , Acidose/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Desidrogenases de Carboidrato/genética , Desidrogenases de Carboidrato/metabolismo , Linhagem Celular Tumoral , Glioma/genética , Glioma/patologia , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Metabolômica , Células-Tronco Neoplásicas/patologia , Microambiente Tumoral
17.
J Plant Physiol ; 260: 153390, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33667937

RESUMO

To maximize breeding and exploitation of disease resistance traits for managing apple replant disease (ARD), it is of great importance to understand the mechanisms of apple root resistance. Currently, little is known about the functions of the specific genes that confer resistance traits in apple root. In this study, molecular, biochemical, and genetic approaches allowed an in-depth understanding of the role of the MdPR4 gene in the defense response of apple root. The MdPR4 encoding gene showed upregulation following ARD pathogen inoculation in our previous transcriptome data. Subcellular localization analyses revealed that MdPR4 is localized on the plasma membrane, endoplasmic reticulum, and apoplast, which is mainly determined by its signal peptide. Molecular docking analysis between MdPR4 protein with chitin molecule and in vitro MdPR4 chitin affinity assay proved its chitin-binding ability, which provided evidence for its role in chitin-mediated immune responses. Purified MdPR4 protein and MdPR4 overexpressed apple callus inhibited spore germination and mycelial growth of ARD-related Fusarium spp. pathogens. These data support the conclusion that MdPR4 is a chitin-binding protein in apple vegetative tissues that may play an important role in defense activation in response to ARD pathogen infection.


Assuntos
Fusarium/fisiologia , Malus/imunologia , Proteínas de Membrana/genética , Doenças das Plantas/imunologia , Imunidade Vegetal/genética , Proteínas de Plantas/genética , Quitina/metabolismo , Fusarium/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas/imunologia , Malus/genética , Proteínas de Membrana/imunologia , Proteínas de Membrana/metabolismo , Simulação de Acoplamento Molecular , Micélio/crescimento & desenvolvimento , Micélio/fisiologia , Doenças das Plantas/microbiologia , Proteínas de Plantas/imunologia , Proteínas de Plantas/metabolismo , Esporos Fúngicos/crescimento & desenvolvimento
18.
Anal Chim Acta ; 1155: 338342, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33766316

RESUMO

Spatially resolved metabolomics offers unprecedented opportunities for elucidating metabolic mechanisms during cancer progression. It facilitated the discovery of aberrant cellular metabolism with clinical application potential. Here, we developed a novel strategy to discover cancer tissue relevant metabolic signatures by high spatially resolved metabolomics combined with a multicellular tumor spheroid (MCTS) in vitro model. Esophageal cancer MCTS were generated using KYSE-30 human esophageal cancer cells to fully mimic the 3D microenvironment under physiological conditions. Then, the spatial features and temporal variation of metabolites and metabolic pathways in MCTS were accurately mapped by using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) with a spatial resolution at ∼12 µm. Metabolites, such as glutamate, tyrosine, inosine and various types of lipids displayed heterogeneous distributions in different microregions inside the MCTS, revealing the metabolic heterogenicity of cancer cells under different proliferative states. Subsequently, through joint analysis of metabolomic data of clinical cancer tissue samples, cancer tissue relevant metabolic signatures in esophageal cancer MCTS were identified, including glutamine metabolism, fatty acid metabolism, de novo synthesis phosphatidylcholine (PC) and phosphatidylethanolamine (PE), etc. In addition, the abnormal expression of the involved metabolic enzymes, i.e., GLS, FASN, CHKA and cPLA2, was further confirmed and showed similar tendencies in esophageal cancer MCTS and cancer tissues. The MALDI-MSI combined with MCTS approach offers molecular insights into cancer metabolism with real-word relevance, which would potentially benefit the biomarker discovery and metabolic mechanism studies.


Assuntos
Neoplasias Esofágicas , Metabolômica , Humanos , Metaboloma , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Esferoides Celulares , Microambiente Tumoral
19.
Small ; 17(10): e2006508, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33569918

RESUMO

Multi-modality cancer diagnosis techniques based on the second near-infrared window fluorescence (NIR-II FL, 1000-1700 nm) imaging have become the focus of research attention. For such multimodality probes, how to take advantage of the tumor microenvironments (TME) characteristics to better image diseases and combine efficient therapeutics to achieve theranostics is still a big challenge. Herein, a novel TME-activated nanosystem (FMSN-MnO2 -BCQ) employing degradable silica-based nanoplatform is designed, adjusting the ratio of intratumoral hydrogen peroxide (H2 O2 )/glutathione (GSH) for magnetic resonance imaging (MRI)/NIR-II FL imaging and self-reinforcing chemodynamic therapy (CDT). Innovative bovine serum albumin (BSA)-modified fusiform-like mesoporous silica nanoparticles (FMSN) is fabricated as a carrier for NIR-II small molecule (CQ4T) and MRI reporter MnO2 . Remarkably, the BSA modification helped to achieve the dual-functions of high biocompatibility and enhance NIR-II fluorescence. The FMSN-MnO2 -BCQ with FMSN framework featuring a stepwise degradability in tumor interior released MnO2 and BCQ nanoparticles. Through the specific degradation of MnO2 by the TME, the produced Mn2+ ions are effectively exerted Fenton-like activity to generate hydroxyl radical (•OH) from endogenous H2 O2 to eradicate tumor cells. More importantly, the GSH depletion due to the synergistic effect of tetrasulfide bond and MnO2 in turn induced the oxidative cytotoxicity for self-reinforcing CDT.


Assuntos
Nanopartículas , Neoplasias , Humanos , Peróxido de Hidrogênio , Imageamento por Ressonância Magnética , Compostos de Manganês , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Imagem Óptica , Óxidos , Dióxido de Silício , Nanomedicina Teranóstica , Microambiente Tumoral
20.
Adv Mater ; 33(14): e2008061, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33634897

RESUMO

Cell-membrane-coated nanoparticles (CCNPs) that integrate the biophysiological advantages of cell membranes with the multifunctionalities of synthetic materials hold great promise in cancer immunotherapy. However, strategies have yet to be revealed to further improve their immunotherapeutic efficacy. Herein, a polymer multicellular nanoengager (SPNE) for synergistic second-near-infrared-window (NIR-II) photothermal immunotherapy is reported. The nanoengager consists of an NIR-II absorbing polymer as the photothermal core, which is camouflaged with fused membranes derived from immunologically engineered tumor cells and dendritic cells (DCs) as the cancer vaccine shell. In association with the high accumulation in lymph nodes and tumors, the multicellular engagement ability of the SPNE enables effective cross-interactions among tumor cells, DCs, and T cells, leading to augmented T cell activation relative to bare or tumor-cell-coated nanoparticles. Upon deep-tissue penetrating NIR-II photoirradiation, SPNE eradicates the tumor and induces immunogenic cell death, further eliciting anti-tumor T cell immunity. Such a synergistic photothermal immunotherapeutic effect eventually inhibits tumor growth, prevents metastasis and procures immunological memory. Thus, this study presents a general cell-membrane-coating approach to develop photo-immunotherapeutic agents for cancer therapy.


Assuntos
Imunoterapia/métodos , Raios Infravermelhos , Nanomedicina/métodos , Polímeros , Nanomedicina Teranóstica/métodos , Animais , Humanos
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