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1.
Cancers (Basel) ; 13(19)2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34638461

RESUMO

Immune checkpoint inhibitor (ICI) therapy has been a paradigm shift in the treatment of cancer. ICI therapy results in durable responses and survival benefit for a large number of tumor types. Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has shown great efficacy treating EGFR mutant lung cancers; however, all patients eventually develop resistance. ICI therapy has not benefitted EGFR mutant lung cancer. Herein, we employed stable isotope labeling by amino acids in cell culture (SILAC) quantitative mass spectrometry-based proteomics to investigate potential immune escape molecular mechanisms in osimertinib resistant EGFR mutant lung adenocarcinoma by interrogating the alterations in the human leukocyte antigen (HLA) Class I-presented immunopeptidome, Class I-interactome, and the whole cell proteome between isogenic osimertinib-sensitive and -resistant human lung adenocarcinoma cells. Our study demonstrates an overall reduction in HLA class I-presented immunopeptidome and downregulation of antigen presentation core complex (e.g., TAP1 and ERAP1/2) and immunoproteasome in osimertinib resistant lung adenocarcinoma cells. Several key components in autophagy pathway are differentially altered. S100 proteins and SLC3A2 may play critical roles in reduced antigen presentation. Our dataset also includes ~1000 novel HLA class I interaction partners and hundreds of Class I-presented immunopeptides in EGFR mutant lung adenocarcinoma. This large-scale unbiased proteomics study provides novel insights and potential mechanisms of immune evasion of EGFR mutant lung adenocarcinoma.

2.
Front Nutr ; 8: 751010, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660671

RESUMO

Animal antimicrobial peptides (AMPs), known as broad-spectrum and high-efficiency antibacterial activity, are important effector molecules in innate immune system. AMPs not only have antimicrobial, antiviral and antitumor effects but also exhibit important effects in vivo, such as anti-inflammatory response, recruiting immune cells, promoting epithelial damage repair, and promoting phagocytosis of bacteria. However, research on the application of AMPs is incomplete and controversial. This review mainly introduces the classification of AMPs, biological functions, as well as the mechanisms of action, expression rules, and nutrition regulation from three perspectives, aiming to provide important information for the application of AMPs.

3.
ACS Appl Mater Interfaces ; 13(39): 46361-46374, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34579526

RESUMO

Size expansion can effectively improve tumor accumulation of nanocarriers where precise control is required. A dual-responsive nanocarrier stimulated by both endogenous pH and exogenous heat stimuli can change its size. Herein, a nanoparticle composed of poly(N,N-diethyl acrylamide) (PDEAA) and poly(2-(diisopropylamino) ethyl methacrylate) (PDPA) is developed. The antitumor drug celastrol (CLT) and the photosensitizer indocyanine green (ICG) are then loaded in it to form CIPP. ICG generates heat under near-infrared (NIR) stimulation to kill tumor cells and enhance CIPP penetration. Meanwhile, CIPP expands in response to hyperthermia and acid tumor microenvironments, preventing itself from returning to the blood flow, thus accumulating in tumor sites. Ultimately, the acidic lysosomal environment in tumor cells disintegrates CIPP to release CLT, directly inducing immunogenic cell death and sensitizing tumor cells for hyperthermia by disrupting the interaction of heat shock protein 90 and P50cdc37. Most of the tumors in B16F10-bearing mice are eradicated after single laser irradiation. The dual-responsive CIPP with multiple functions and simple design displays a synergistic antitumor effect. This study provides a basis for developing size-expandable stimulus-responsive drug delivery systems against tumors.

4.
Front Oncol ; 11: 721249, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589427

RESUMO

The past two decades witnessed a revolution in our understanding of host-microbiota interactions that led to the concept of the super-organism consisting of a eukaryotic part and a prokaryotic part. Owing to the critical role of gut microbiota in modulating the host immune system, it is not beyond all expectations that more and more evidence indicated that the shift of gut microbiota influenced responses to numerous forms of cancer immunotherapy. Therapy targeting gut microbiota is becoming a promising strategy to improve cancer immunotherapy. In this review, we discuss the role of the gut microbiota in response to cancer immunotherapy, the mechanisms that the gut microbiota influences cancer immunotherapy, and therapeutic strategies targeting gut microbiota to improve cancer immunotherapy.

5.
Oxid Med Cell Longev ; 2021: 9957908, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539976

RESUMO

Background: Pathological changes of the adrenal gland and the possible underlying molecular mechanisms are currently unclear in the case of atherosclerosis (AS) combined with chronic stress (CS). Methods: New Zealand white rabbits were used to construct a CS and AS animal model. Proteomics and bioinformatics were employed to identify hub proteins in the adrenal gland related to CS and AS. Hub proteins were detected using immunohistochemistry, immunofluorescence assays, and Western blotting. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to analyze the expression of genes. In addition, a neural network model was constructed. The quantitative relationships were inferred by cubic spline interpolation. Enzymatic activity of mitochondrial citrate synthase and OGDH was detected by the enzymatic assay kit. Function of citrate synthase and OGDH with knockdown experiments in the adrenal cell lines was performed. Furthermore, target genes-TF-miRNA regulatory network was constructed. Coimmunoprecipitation (IP) assay and molecular docking study were used to detect the interaction between citrate synthase and OGDH. Results: Two most significant hub proteins (citrate synthase and OGDH) that were related to CS and AS were identified in the adrenal gland using numerous bioinformatic methods. The hub proteins were mainly enriched in mitochondrial proton transport ATP synthase complex, ATPase activation, and the AMPK signaling pathway. Compared with the control group, the adrenal glands were larger and more disordered, irregular, and necrotic in the AS+CS group. The expression of citrate synthase and OGDH was higher in the AS+CS group than in the control group, both at the protein and mRNA levels (P < 0.05). There were strong correlations among the cross-sectional areas of adrenal glands, citrate synthase, and OGDH (P < 0.05) via Spearman's rho analysis, receiver operating characteristic curves, a neural network model, and cubic spline interpolation. Enzymatic activity of citrate synthase and OGDH increased under the situation of atherosclerosis and chronic stress. Through the CCK8 assay, the adrenal cell viability was downregulated significantly after the knockdown experiment of citrate synthase and OGDH. Target genes-TF-miRNA regulatory network presented the close interrelations among the predicted microRNA, citrate synthase and OGDH. After Coimmunoprecipitation (IP) assay, the result manifested that the citrate synthase and OGDH were coexpressed in the adrenal gland. The molecular docking study showed that the docking score of optimal complex conformation between citrate synthase and OGDH was -6.15 kcal/mol. Conclusion: AS combined with CS plays a significant role on the hypothalamic-pituitary-adrenal (HPA) axis, promotes adrenomegaly, increases the release of glucocorticoid (GC), and might enhance ATP synthesis and energy metabolism in the body through citrate synthase and OGDH gene targets, providing a potential research direction for future related explorations into this mechanism.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34487891

RESUMO

OBJECTIVE: We compared the in vitro clot-capturing efficiencies (CCEs) of commercially available retrievable inferior vena cava (IVC) filters. METHODS: Four types of commercially available retrievable IVC filters were included in the present study: Denali (BD, Franklin Lakes, NJ), OptEase (Cordis Corp, Hialeah, Fla), Celect (Cook Medical, Bloomington, Ind), and Option (Argon Medical Devices, Frisco, Tex). The CCE of each IVC filter for 10 different size clots, ranging from 2 mm × 10 mm to 6 mm × 20 mm, was analyzed using a venous flow simulator. RESULTS: When ≥4 × 10-mm clots were used, the CCEs were 100% for all four types of IVC filters in a 20-mm-diameter simulated IVC filter. However, when ≤3 × 20-mm clots were used, the CCEs were significantly different among the four types of filters in a 20-mm-diameter simulated IVC, with the Denali showing the highest CCE, followed by the OptEase, Celect, and Option. When ≥6 × 10-mm clots were used, the CCEs were 100% for all four types of IVC filters in the 25-mm-diameter simulated IVC. However, when ≤5 × 20-mm clots were used, the CCEs were significantly different among the four types of filters in the 25-mm-diameter simulated IVC, with the Denali showing the highest CCE. When ≤5 × 10-mm clots were used, the CCEs were significantly lower in the 25-mm-diameter simulated IVC than in the 20-mm-diameter simulated IVC for all four types of IVC filters, with Option showing the greatest change in CCEs, followed by the Celect, OptEase, and Denali. CONCLUSIONS: The CCEs were significantly different among the four IVC filters and were significantly lower for the smaller size clots than for the larger size clots and for the larger diameter simulated IVC than for the smaller diameter simulated IVC.

7.
Nanoscale ; 13(36): 15267-15277, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34477185

RESUMO

Metastasis is a major sign of malignant tumors which plays a vital role in cancer-related death. Suppressing metastasis is an important way to improve the survival rate of cancer patients. Herein, multifunctional PEG-LAM-PPS nanoparticles (nPLPs) are fabricated as both nanocarriers and anti-metastatic agents for tumor treatment. In this system, laminarin sulfate (LAM) suppresses metastasis by reducing heparinase and protecting the extracellular matrix; the ROS-sensitive polypropylene sulfide (PPS) improves the release of the loaded drug in the tumor microenvironment. This is the first time that laminarin sulfate has been used as a carrier to inhibit the expression of heparinase and treat melanoma lung metastasis. The blank nanoparticles are excellently safe and showed high anti-metastatic efficacy in melanoma lung metastatic mouse models, reducing metastatic nodules by 60%. They significantly improved the anti-tumor efficacy of the loaded drug doxorubicin, provided ∼33% further reduction of the tumor volume and 50% further reduction of the metastatic nodule number compared with free doxorubicin. Thus, these simple and versatile micellar nanoparticles composed of biocompatible materials offer a promising vehicle for treating invasive solid tumors and metastases.


Assuntos
Antineoplásicos , Nanopartículas , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Regulação para Baixo , Doxorrubicina/farmacologia , Heparina Liase , Humanos , Camundongos , Micelas , Espécies Reativas de Oxigênio
8.
J Chromatogr Sci ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491317

RESUMO

A simple high performance liquid chromatography (HPLC) method was developed and validated for the determination of coumarin-3-carboxylic acid analogues (C3AA) in rat plasma and a preliminary study on pharmacokinetics. Ferulic acid (FA) was used as the internal standard substance, and coumarin-3-carboxylic acid (C3A) was used as a substitute for quantitative C3AA. After protein precipitation with methanol, the satisfactory separation was achieved on an ODS2 column when the temperature was maintained at 30 ± 2°C. The correlation coefficient r in the C3A linear equation is equal to 0.9990. Pharmacokinetic parameters for t1/2, Tmax, Cmax, area under the curve (AUC)0-t, average residence time (MRT), apparent volume of distribution (V z/F) and clearance (Cl/F) were 1.89 ± 0.03 h, 0.39 ± 0.14 h, 1.81 ± 0.10 g· mL-1 ·h, 7.88 ± 0.24 g·mL-1·h, 3.23 ± 0.14 h, 0.43 ± 0.03 (mg·kg-1)·(g·mL-1)-1·h-1, respectively. The high performance liquid chromatography-photo diode array detector (HPLC-PDA) method established in this study can be used to separate and determine the content of C3AA in plasma of rats after 60% ethanol extraction by gavage. The plasma concentration-time curve and pharmacokinetic parameters reflect the absorption of C3AA in rat blood after oral administration to some extent.

9.
Front Microbiol ; 12: 688839, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484139

RESUMO

Corn germ meal (CGM) and corn gluten feed (CGF) are the two main corn byproducts (CBs) obtained from corn starch extraction. Due to their high fiber content, low protein content, and severe imbalance of amino acid, CBs are unable to be fully utilized by animals. In this study, the effect of microorganism, proteases, temperature, solid-liquid ratio, and time on nutritional properties of CB mixture feed (CMF) was investigated with the single-factor method and the response surface method to improve the nutritional quality and utilization of CBs. Fermentation with Pichia kudriavzevii, Lactobacillus plantarum, and neutral protease notably improved the nutritional properties of CMF under the fermentation conditions of 37°C, solid-liquid ratio (1.2:1 g/ml), and 72 h. After two-stage solid-stage fermentation, the crude protein (CP) and trichloroacetic acid-soluble protein (TCA-SP) in fermented CMF (FCMF) were increased (p < 0.05) by 14.28% and 25.53%, respectively. The in vitro digestibility of CP and total amino acids of FCMF were significantly improved to 78.53% and 74.94%, respectively. In addition, fermentation degraded fiber and provided more organic acids in the CMF. Multiple physicochemical analyses combined with high-throughput sequencing were performed to reveal the dynamic changes that occur during a two-stage solid-state fermentation process. Generally, Ascomycota became the predominant members of the community of the first-stage of fermentation, and after 36 h of anaerobic fermentation, Paenibacillus spp., Pantoea spp., and Lactobacillales were predominant. All of these processes increased the bacterial abundance and lactic acid content (p < 0.00). Our results suggest that two-stage solid-state fermentation with Pichia kudriavzevii, Lactobacillus plantarum, and protease can efficiently improve protein quality and nutrient utilization of CMF.

10.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(4): 410-415, 2021 Jul 30.
Artigo em Chinês | MEDLINE | ID: mdl-34363368

RESUMO

Biodegradable vascular stents have better biocompatibility than drug-eluting stents. The blood vessels are rebuilt and degraded after normal physiological functions are restored. Due to it will not stay in the body for a long time and the patients don't need taking anti-rejection drugs all the time, it becomes the focus of attention in the treatment of coronary heart disease. This article introduced the development history of biodegradable stents and reviewed the research status of several different materials of vascular stents (animals or humans) in vivo and pointed out the existing problems. And it also predicted the research direction of biodegradable vascular stents.


Assuntos
Implantes Absorvíveis , Stents Farmacológicos , Animais , Humanos , Stents
11.
Mol Oral Microbiol ; 36(5): 278-290, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34351080

RESUMO

Zinc (Zn2+ ) is an essential divalent trace metal for living cells. Intracellular zinc homeostasis is critical to the survival and virulence of bacteria. Thus, the frequent fluctuations of salivary zinc, caused by the low physiological level and the frequent exogenous zinc introduction, present a serious challenge for bacteria colonizing the oral cavity. However, the regulation strategies to keep intracellular Zn2+ homeostasis in Streptococcus mutans, an important causative pathogen of dental caries, are unknown. Because zinc uptake is primarily mediated by an ATP-binding ABC transporter AdcABC in Streptococcus strains, we examined the function of AdcABC and transcription factor AdcR in S. mutans in this study. The results demonstrated that deletion of either adcA or adcCB gene impaired the growth but enhanced the extracellular polymeric matrix production in S. mutans, both of which could be relieved after excessive Zn2+ supplementation. Using RNA sequencing analysis, quantitative reverse transcription polymerase chain reaction examination, LacZ-reporter studies, and electrophoretic mobility shift assay, we showed that a MarR (multiple antibiotic resistance regulator) family transcription factor, AdcR, negatively regulates the expression of the genes adcR, adcC, adcB, and adcA by acting on the adcRCB and adcA promoters in response to Zn2+ concentration in their environmental niches. The deletion of adcR increases the sensitivity of S. mutans to excessive Zn2+ supply. Taken together, our findings suggest that Adc regulon, which consists of a Zn2+ uptake transporter AdcCBA and a Zn2+ -responsive repressor AdcR, plays a prominent role in the maintenance of intracellular zinc homeostasis of S. mutans.


Assuntos
Cárie Dentária , Regulon , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Homeostase , Humanos , Regulon/genética , Streptococcus mutans/genética , Streptococcus mutans/metabolismo , Zinco/metabolismo
12.
mSystems ; 6(4): e0078821, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34427509

RESUMO

The ability of Streptococcus mutans to survive and cause dental caries is dependent on its ability to metabolize various carbohydrates, accompanied by extracellular polysaccharide synthesis and biofilm formation. Here, the role of an rel competence-related regulator (RcrR) in the regulation of multiple sugar transportation and biofilm formation is reported. The deletion of the rcrR gene in S. mutans caused delayed growth, decreased biofilm formation ability, and affected the expression level of its multiple sugar transportation-related genes. Transcriptional profiling revealed 17 differentially expressed genes in the rcrR mutant. Five were downregulated and clustered with the sugar phosphotransferase (PTS) systems (mannitol- and trehalose-specific PTS systems). The conserved sites bound by the rcrR promoter were then determined by electrophoretic mobility shift assays (EMSAs) and DNase I footprinting assays. Furthermore, a potential binding motif in the promoters of the two PTS operons was predicted using MEME Suite 5.1.1. RcrR could bind to the promoter regions of the two operons in vitro, and the sugar transporter-related genes of the two operons were upregulated in an rcrR-overexpressing strain. In addition, when RcrR-binding sites were deleted, the growth rates and final yield of S. mutans were significantly decreased in tryptone-vitamin (TV) medium supplemented with different sugars, but not in absolute TV medium. These results revealed that RcrR acted as a transcription activator to regulate the two PTS systems, accompanied by multiple sugar transportation and biofilm formation. Collectively, these results indicate that RcrR is a critical transcription factor in S. mutans that regulates bacterial growth, biofilm formation, and multiple sugar transportation. IMPORTANCE The human oral cavity is a constantly changing environment. Tooth decay is a commonly prevalent chronic disease mainly caused by the cariogenic bacterium Streptococcus mutans. S. mutans is an oral pathogen that metabolizes various carbohydrates into extracellular polysaccharides (EPSs), biofilm, and tooth-destroying lactic acid. The host diet strongly influences the availability of multiple carbohydrates. Here, we showed that the RcrR transcription regulator plays a significant role in the regulation of biofilm formation and multiple sugar transportation. Further systematic evaluation of how RcrR regulates the transportation of various sugars and biofilm formation was also conducted. Notably, this study decrypts the physiological functions of RcrR as a potential target for the better prevention of dental caries.

13.
J Phys Chem Lett ; 12(32): 7866-7877, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34382813

RESUMO

Perovskite solar cells (PSC) are a favorable candidate for next-generation solar systems with efficiencies comparable to Si photovoltaics, but their long-term stability must be proven prior to commercialization. However, traditional trial-and-error approaches to PSC screening, development, and stability testing are slow and labor-intensive. In this Perspective, we present a survey of how machine learning (ML) and autonomous experimentation provide additional toolkits to gain physical understanding while accelerating practical device advancement. We propose a roadmap for applying ML to PSC research at all stages of design (compositional selection, perovskite material synthesis and testing, and full device evaluation). We also provide an overview of relevant concepts and baseline models that apply ML to diverse materials problems, demonstrating its broad relevance while highlighting promising research directions and associated challenges. Finally, we discuss our outlook for an integrated pipeline that encompasses all design stages and presents a path to commercialization.

14.
Aging (Albany NY) ; 13(15): 19529-19541, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34349039

RESUMO

AIMS: Premenstrual dysphoric disorder (PMDD) is a psychiatric condition that is associated with the menstrual cycle. Elucidation of the neural regulation mechanisms of brain reactivity to emotional stimuli among women with PMDD may inform PMDD treatment. METHODS: Eighty-six women (42 PMDD, 44 healthy controls) were allocated into two groups (anger-induced group: 23 PMDD vs. 23 controls; depression-induced group: 19 PMDD vs. 21 controls). During the luteal phases of the menstrual cycle, all the women were subjected to functional magnetic resonance imaging (fMRI). fMRI resting-state scans were performed before and after the study participants had performed an emotional stimuli task. After the emotional stimuli task, emotional status of the participants were evaluated by Self-Rating Depression Scales (SDS) and Trait Anger Expression Inventory-II (STAXI-II). In addition, all the participants were requested to complete the Eysenck Personality Questionnaire (EPQ) and the Twenty-Item Toronto Alexithymia Scale (TAS-20). RESULTS: Compared to healthy controls, all women with PMDD exhibited significantly high scores in Tas-20 (p<0.001), higher neuroticism and psychoticism scores as well as significantly low extraversion and social desirability scores (p<0.05). Compared to the controls, f-MRI revealed that PMDD women had elevated ReHo in the middle frontal gyrus (BA10), temporal lobe (BA42), left cerebellum (BA37), as well as decreased activation in the precuneus (BA7), superior frontal gyrus (BA8), lobulus paracentralis (BA6), and right cerebellum (BA48) (p<0.05). Moreover, depression stimuli showed that women with PMDD had elevated ReHo levels in the middle frontal gyrus (BA11), the middle gyrus (BA47) and in the cingulate gyrus (BA23) vs. healthy controls (p<0.05). CONCLUSIONS: Women with more neuroticism and psychoticism, less extraversion and social desirability tend to report PMDD symptoms. Women with this condition experience difficulties in regulating emotions during the luteal phase of the menstrual cycle. Abnormal ReHo levels in the precuneus, superior frontal gyrus, lobulus paracentralis, and right cerebellum may contribute to anger dysregulation. Hypoactivation in the middle frontal gyrus, the middle gyrus and the cingulate gyrus may be generally associated with depression dysregulation in PMDD.

15.
Neuroimage ; 241: 118430, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34314848

RESUMO

PURPOSE: Heating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites. METHOD: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC). RESULTS: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI. DISCUSSION: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Análise de Dados , Bases de Dados Factuais/normas , Imageamento por Ressonância Magnética/normas , Espectroscopia de Ressonância Magnética/normas , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos
16.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(4): 612-618, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34323039

RESUMO

Objective: To develop a pirarubicin (THP) and vinorelbine (VRL) codelivery nano-micellar system (T+V-CS micelles) of pirarubicin (THP) and vinorelbine (VRL) by using chondroitin sulfate-cholesterol polymers (CS-Chol) and DSPE-mPEG 2000 and to evaluate the therapeutic efficacy of the codelivery nano-micelles in breast cancer treatment. Methods: T+V-CS micelles were prepared by ultrasonic-dialysis method, and the physicochemical characterization were evaluated using multiple technological means. The anti-tumor efficacy of T+V-CS micelles in vitro was evaluated by MTT assay and cell cycle arrest analysis. Evaluation of the therapeutic effect of T+V-CS micelles in vivo was carried out on xenograft 4T1 murine breast cancer bearing BALB/c mice model. Results: T+V-CS micelles displayed a nearly spherical shape when observed through transmission electron microscope. The particle size and polydispersity indexes (PDI) of T+V-CS micelles was (155.5±4.5) nm and 0.170±0.003 respectively, while the Zeta potential was (-23.0±0.9) mV. Meanwhile, T+V-CS micelles demonstrated high encapsulation efficiency of (81.87±2.56)% for THP and (87.54±2.82)% for VRL and a high overall drug loading efficiency of (10.20±1.20)%. In vitro and in vivo studies of the therapeutic efficacy of breast cancer showed that T+V-CS micelles had synergistic anti-tumor effect and induced increased G 2/M cell cycle arrest in 4T1 cells, which could significantly inhibit tumor growth and prolong survival compared with the therapeutic efficacy of micelles loaded with a single kind of drug or free drug solutions. Conclusion: The study showed that T+V-CS micelles had excellent anti-tumor effect, offering a reference to the clinical treatment of breast cancer.


Assuntos
Antineoplásicos , Neoplasias da Mama , Animais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Doxorrubicina/análogos & derivados , Portadores de Fármacos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Micelas , Polietilenoglicóis/uso terapêutico , Vinorelbina/uso terapêutico
17.
Neuroimage Clin ; 31: 102763, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34280836

RESUMO

PURPOSE: Focal cortical dysplasia (FCD) is a major cause of drug-resistant epilepsy; however the underlying epileptogenic mechanisms of FCD metabolism in epilepsy patients remain unclear. The aim of this study is to detect alterations of γ-aminobutyric acid (GABA), glutathione (GSH), and the composite of glutamate and glutamine (Glx) in MRI-typical and neuropathologically confirmed FCD-associated epilepsy using Hadamard Encoding and Reconstruction of Mega-Edited Spectroscopy (HERMES). MATERIALS AND METHODS: Fourteen epileptic patients suspected to be caused by FCD and 14 healthy controls were enrolled prospectively in this study; all subjects underwent a 3 T MRI scan, including 3D T1 weighted imaging and HERMES. The GABA signal detected by HERMES also contains signals from macromolecules and homocarnosine, so it is referred as GABA+. Signals of GABA+, GSH and Glx detected by HERMES from tumor foci, contralateral cerebral regions, and healthy controls were quantified using Gannet. Fitting errors and signal to noise ratios (SNRs) of GABA + signals were also recorded. Differences of GABA+, GSH, Glx, fitting error and SNR of GABA + among three groups were analyzed using linear mixed effects models. RESULTS: Twelve FCD-associated epilepsy patients (7 females, aged 21.9 ± 9.3 years) and 12 matched healthy controls (7 females, aged 22.8 ± 9.8 years) were finally enrolled in this study. ANOVA results indicated that GABA levels were significantly increased in FCD foci compared with contralateral regions (p = 0.008) and with healthy controls (p = 0.003), while no difference was found in GSH and Glx levels. No difference of fitting errors or SNR of GABA + was found among FCD foci, contralateral regions and healthy controls. CONCLUSIONS: Increased GABA levels were found in FCD foci that indicated GABA may play a central role in the pathophysiology of FCD patients with epilepsy.


Assuntos
Epilepsia , Malformações do Desenvolvimento Cortical , Epilepsia/diagnóstico por imagem , Feminino , Glutationa , Humanos , Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical/complicações , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Ácido gama-Aminobutírico
18.
J Inorg Biochem ; 223: 111558, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34329998

RESUMO

Photo-chemotherapy (PCT) reveals great potential in hepatocellular carcinoma (HCC) treatment, therefore the construct of smart PCT nano-agents with high photothermal conversion efficiency and accurate drug delivery is of great significant. Herein, a novel hybrid nanomaterial MGO-TCA-FA has been designed and constructed by grafting the triformyl cholic acid (TCA) and folic acid (FA) on the surface of Fe3O4 modified graphene oxide (MGO). The doxorubicin hydrochloride (DOX) as a model drug could be effectively loaded on the MGO-TCA-FA via hydrogen bonding and π-π stacking (the drug loading amount was 1040 mg/g). The formed MGO-TCA-FA@DOX has been developed to be an effective PCT nanoplatform with the advantages of multiple-targeted drug delivery, near-infrared light (NIR) and pH triggered drug release, and photothermal conversion efficiency. In vitro experiments showed that compared with other cancer cells and normal liver cells, MGO-TCA-FA@DOX could specifically target liver cancer cells and presented significant killing ability to liver cancer cells. More importantly, in vivo experiments indicated that PCT synergistic therapy (MGO-TCA-FA@DOX) revealed the best tumor inhibition (the tumor inhibition rate was about 85%) compared with chemotherapy and photothermal therapy alone. Thus, this study supplied a viable multiple-targeted PCT nano-agent for chemo-photothermal combination therapy of liver cancer.

19.
Biomaterials ; 275: 120902, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34087588

RESUMO

Activated fibroblasts are critical contributors to renal interstitial fibrosis thus becoming the cellular target for fibrosis treatment. Previously, microRNA 29 b (miR-29 b) is shown to be down-regulated in various animal models of renal fibrosis. Herein, we describe a facile strategy to achieve localized and sustained delivery of therapeutic microRNA to the kidney via a host-guest supramolecular hydrogel. Specifically, cationic bovine serum albumin is used to complex with miR-29 b to afford nanocomplexes (cBSA/miR-29 b), which is proven to specifically inhibit fibroblast activation in a dose-dependent manner in vitro. Following unilateral ureteral obstruction in mice, a single injection of the hydrogel loaded with cBSA/miR-29 b in vivo, significantly down-regulated proteins and genes related to fibrosis for up to 21 days without affecting the normal liver or kidney functions. Overall, the localized delivery of cBSA/miR-29 b via a host-guest supramolecular hydrogel represents a safe and effective intervention strategy to delay and reverse the progression of interstitial renal fibrosis.


Assuntos
Hidrogéis , Nefropatias , MicroRNAs , Obstrução Ureteral , Animais , Preparações de Ação Retardada , Fibrose , Rim/patologia , Nefropatias/patologia , Nefropatias/terapia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/uso terapêutico , Obstrução Ureteral/patologia , Obstrução Ureteral/terapia
20.
Quant Imaging Med Surg ; 11(6): 2560-2571, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34079723

RESUMO

Background: Frailty is a geriatric condition characterized by a decreased reserve. The Edmonton frailty scale (EFS) has been widely used as an assessment tool in clinical practice. However, the brain's underlying pathophysiological changes in frailty and their associations with the EFS remain unclear. This study aimed to explore the associations between brain volumetry and relaxometry signatures and the EFS (and each domain score of the EFS) in frailty. Methods: A total of 40 non-demented subjects were enrolled in this prospective study. Frailty assessment was performed for each subject according to the EFS. All subjects underwent synthetic magnetic resonance imaging (MRI) (MAGnetic resonance image Compilation, MAGiC) and three-dimensional fast spoiled gradient-recalled echo (3D-FSPGR) T1-weighted structural image acquisitions on a 3.0 T MR scanner. Brain segmentation was performed based on quantitative values obtained from the MAGiC and 3D-FSPGR images. Volumetry and relaxometry of the global brain and regional gray matter (GM) were also obtained. The associations between the total EFS score (and the score of each domain) and the brain's volumetry and relaxometry were investigated by partial correlation while eliminating the effects of age. Multiple comparisons of regional GM volumetry and relaxometry analyses were controlled by false discovery rate (FDR) correction. All data were analyzed using the SPSS 13.0 statistical package (IBM, Armonk, NY, USA) and MATLAB (MathWorks, Natick, MA, USA). Results: For global volumetry, significant correlations were found between multiple global volumetry parameters and the EFS, as well as the cognition score, functional independence score, nutrition score, and functional performance score (P<0.05). For global relaxometry, notable positive correlations were found between the T2 values of gray and white matter (WM) and the EFS (r=0.357, P=0.026; r=0.357, P=0.026, respectively). Significant correlations were also identified between the T2 value of GM, the T1, T2, and PD values of WM, and the cognition score (r=0.426, P=0.007; r=0.456, P=0.003; r=0.377, P=0.018; r=0.424, P=0.007, respectively), functional independence score (r=-0.392, P=0.014; r=-0.611, P<0.001; r=-0.367, P=0.022; r=-0.569, P<0.001, respectively), and functional performance score (r=0.337, P=0.036; r=0.472, P=0.002; r=0.354, P=0.027; r=0.376, P=0.018, respectively). For regional GM volumetry, multiple regions showed significant negative correlations with the EFS (P<0.05). Notable negative correlations were found between multiple regional GM volume and the functional independence score (P<0.05). For regional GM relaxometry, the T1 and T2 values of several regions showed significant negative correlations with the functional independence score (T1 value of caudate, r=-0.617, P<0.001; T2 value of insula, r=-0.510, P=0.015; T2 value of caudate, r=-0.633, P<0.001, respectively). No significant correlation was found between the domain scores of the EFS and regional GM PD values (P>0.05). Conclusions: In conclusion, brain volumetry and relaxometry signatures showed strong associations with the EFS and some EFS domain scores in frailty. These associations may reveal the possible underlying pathophysiology of the EFS and different domains of the EFS.

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