Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 106
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Mol Syst Biol ; 19(9): e11503, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37602975

RESUMO

Single-cell proteomics aims to characterize biological function and heterogeneity at the level of proteins in an unbiased manner. It is currently limited in proteomic depth, throughput, and robustness, which we address here by a streamlined multiplexed workflow using data-independent acquisition (mDIA). We demonstrate automated and complete dimethyl labeling of bulk or single-cell samples, without losing proteomic depth. Lys-N digestion enables five-plex quantification at MS1 and MS2 level. Because the multiplexed channels are quantitatively isolated from each other, mDIA accommodates a reference channel that does not interfere with the target channels. Our algorithm RefQuant takes advantage of this and confidently quantifies twice as many proteins per single cell compared to our previous work (Brunner et al, PMID 35226415), while our workflow currently allows routine analysis of 80 single cells per day. Finally, we combined mDIA with spatial proteomics to increase the throughput of Deep Visual Proteomics seven-fold for microdissection and four-fold for MS analysis. Applying this to primary cutaneous melanoma, we discovered proteomic signatures of cells within distinct tumor microenvironments, showcasing its potential for precision oncology.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Proteoma , Proteômica , Medicina de Precisão , Microambiente Tumoral
2.
Fish Physiol Biochem ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639895

RESUMO

Identification of specific molecular markers for spermatogonial stem cells in teleost is crucial for enhancing the efficacy of reproductive biotechnologies in aquaculture, such as transplantation and surrogate production in fishes. Since it is not yet possible to distinguish spermatogonial stem cells of European eel (Anguilla anguilla) using specific molecular markers, we isolated spermatogonial cells from immature European eels to find these potential markers. We attempted this by studying three candidate genes: vasa, nanos2, and dnd1. Two vasa (vasa1 and vasa2) genes, nanos2, and dnd1 were identified, characterized, and studied in the muscle, testis, and isolated spermatogonia. Our results showed that vasa1 and vasa2 had the highest levels of expression when measured by qPCR. In situ hybridization and immunochemistry assays showed that the four genes were localized explicitly in type A spermatogonia. However, vasa1 and vasa2 exhibited stronger signals in the immature testicular tissue than the other two potential markers. According to this, vasa1 and vasa2 were found to be the most effective markers for spermatogonial cells in the European eel.

3.
Anal Chem ; 95(50): 18487-18496, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38057291

RESUMO

In situ analysis of biomarkers in the tumor microenvironment (TME) is important to reveal their potential roles in tumor progression and early diagnosis of tumors but remains a challenge. In this work, a bottom-up modular assembly strategy was proposed for a multifunctional protein-nucleic chimeric probe (PNCP) for in situ mapping of cancer-specific proteases. PNCP, containing a collagen anchoring module and a target proteolysis-responsive isothermal amplification sensor module, can be anchored in the collagen-rich TME and respond to the target protease in situ and generate amplified signals through rolling cycle amplification of tandem fluorescent RNAs. Taking matrix metalloproteinase 2 (MMP-2), a tumor-associated protease, as the model, the feasibility of PNCP was demonstrated for the in situ detection of MMP-2 activity in 3D tumor spheroids. Moreover, in situ in vivo mapping of MMP-2 activity was also achieved in a metastatic solid tumor model with high sensitivity, providing a useful tool for evaluating tumor metastasis and distinguishing highly aggressive forms of tumors.


Assuntos
Metaloproteinase 2 da Matriz , Neoplasias , Humanos , Metaloproteinase 2 da Matriz/genética , Peptídeo Hidrolases , Colágeno , Sondas de Ácido Nucleico , Microambiente Tumoral
4.
Eur Radiol ; 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37889272

RESUMO

OBJECTIVES: As a few types of glioma, young high-risk low-grade gliomas (HRLGGs) have higher requirements for postoperative quality of life. Although adjuvant chemotherapy with delayed radiotherapy is the first treatment strategy for HRLGGs, not all HRLGGs benefit from it. Accurate assessment of chemosensitivity in HRLGGs is vital for making treatment choices. This study developed a multimodal fusion radiomics (MFR) model to support radiochemotherapy decision-making for HRLGGs. METHODS: A MFR model combining macroscopic MRI and microscopic pathological images was proposed. Multiscale features including macroscopic tumor structure and microscopic histological layer and nuclear information were grabbed by unique paradigm, respectively. Then, these features were adaptively incorporated into the MFR model through attention mechanism to predict the chemosensitivity of temozolomide (TMZ) by means of objective response rate and progression free survival (PFS). RESULTS: Macroscopic tumor texture complexity and microscopic nuclear size showed significant statistical differences (p < 0.001) between sensitivity and insensitivity groups. The MFR model achieved stable prediction results, with an area under the curve of 0.950 (95% CI: 0.942-0.958), sensitivity of 0.833 (95% CI: 0.780-0.848), specificity of 0.929 (95% CI: 0.914-0.936), positive predictive value of 0.833 (95% CI: 0.811-0.860), and negative predictive value of 0.929 (95% CI: 0.914-0.934). The predictive efficacy of MFR was significantly higher than that of the reported molecular markers (p < 0.001). MFR was also demonstrated to be a predictor of PFS. CONCLUSIONS: A MFR model including radiomics and pathological features predicts accurately the response postoperative TMZ treatment. CLINICAL RELEVANCE STATEMENT: Our MFR model could identify young high-risk low-grade glioma patients who can have the most benefit from postoperative upfront temozolomide (TMZ) treatment. KEY POINTS: • Multimodal radiomics is proposed to support the radiochemotherapy of glioma. • Some macro and micro image markers related to tumor chemotherapy sensitivity are revealed. • The proposed model surpasses reported molecular markers, with a promising area under the curve (AUC) of 0.95.

5.
J Surg Oncol ; 128(2): 207-217, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37036218

RESUMO

BACKGROUND: The aim of this study was to evaluate the safety, efficacy, and oncologic outcomes of neoadjuvant immunotherapy combined with chemotherapy (NICT) group and surgery alone group in the treatment of patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: A series of 232 consecutive patients who underwent surgery with or without NICT from June 2019 to August 2022 were evaluated. We performed propensity score matching between the NICT and surgery alone groups on the basis of estimated propensity scores for each patient. RESULTS: After propensity score matching, data of 137 patients with clinical stages II-IV ESCC, including 85 receiving surgery alone and 52 receiving NICT, were analyzed. Compared with the surgery alone group (301.7 ± 94.4 min), the operation time was significantly longer in the NICT group (333.4 ± 79.7 min). However, there was no significant difference between the two groups in the postoperative complications, intraoperative blood loss, thoracic fluid volume, chest tube duration, lengths of intensive care unit stay and postoperative hospitalization. Additionally, 90-day mortality rate and 30-day readmission were similar in both groups. CONCLUSIONS: Overall, NICT followed by esophagectomy appears to be safe and feasible for locally advanced ESCC. However, further multicenter prospective clinical trials are needed to validate our results.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Neoplasias Esofágicas/cirurgia , Pontuação de Propensão , Carcinoma de Células Escamosas/cirurgia , Terapia Neoadjuvante/métodos , Estudos Prospectivos , Resultado do Tratamento , Imunoterapia , Esofagectomia , Estudos Retrospectivos
6.
Analyst ; 148(8): 1732-1742, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-36938870

RESUMO

Dopamine (DA) plays an essential role in dopaminergic neuronal behavior and disease. However, current detection methods for discriminating the secretion of DA are hampered by the limitations of the requirement for bulky instrumentation and non-intuitive signals. Herein, we have controllably and proportionately integrated molybdenum disulfide (MoS2) with titanium dioxide (TiO2) to prepare MoS2@TiO2 nanocomposites (MoS2@TiO2 NCs) via a facile synthesis method. MoS2@TiO2 NCs with a certain reactant mass ratio have shown a significant enhancement in peroxidase-like activity with superiority of the nanocomposite structure compared to single MoS2 or natural enzyme. The method for catalyzing the decomposition of H2O2 by MoS2@TiO2 NCs and competition for hydroxyl radicals (˙OH) between the chromogenic agent and DA enable a sensitive, specific, and colorimetric DA analysis with a low detection limit of 0.194 µM and a wide linear detection range (0.8 to 100 µM). Because of the favorable detection performance, we were encouraged to explore and finally realize the visual detection of cellular DA secretion that is stimulated in a High-K+ neurocyte environment. Collectively, this method will provide a promising strategy for basic research in neuroscience with its portable, sensitive, and naked-eye detectable performance.


Assuntos
Dopamina , Nanocompostos , Molibdênio/química , Peróxido de Hidrogênio/química , Nanocompostos/química
7.
Org Biomol Chem ; 20(9): 1982-1993, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35179157

RESUMO

A cascade spiroannulation of 2-mercaptoquinoline-3-carbaldehydes with α,α-dicyanoalkenes as well as a cascade spiroannulation of 2-mercaptoquinoline-3-carbaldehydes aldehydes with α-bromocarbonyl compounds was investigated based on a synergistic strategy, providing a series of diverse spiro-fused heterocyclic compounds containing more different functional groups. The features of this strategy directed towards molecular complexity and diversity include step economy, mild conditions, and high bond-forming efficiency, but important polycyclic heterocyclic products, which could be transformed into potential biologically interesting heterocyclic structures.

8.
Appl Opt ; 61(33): 10043-10048, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36606837

RESUMO

Wavefront phase retrieval is one of the most critical problems in adaptive optics. Here, phase retrieval by solving the transport of intensity equation using membrane vibration modes is proposed. Our study shows that the wavefront curvature sensing signal on the pupil can be expanded as a set of corresponding membrane vibration modes. The analytic expressions of the reconstructed phase are given. The coefficients of the functions are obtained by the integral over the pupil and boundary. Several representative Zernike circular and annular polynomials are respectively fitted by eigenfunctions and membrane modes in the absence of noise. In addition, wavefront recovery from noisy curvature data of the simulated atmospheric turbulence phase based on Zernike modes and Kolmogorov spectrum is demonstrated to verify the accuracy and robustness of the proposed method.

9.
Ann Surg ; 273(3): 523-531, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31058700

RESUMO

OBJECTIVE: This study was intended to identify prognostic biomarkers for lymph node (LN)-positive locoregional esophageal squamous cell carcinoma (ESCC) patients. SUMMARY OF BACKGROUND DATA: Surgery is a major treatment for LN-positive locoregional ESCC patients in China. However, patient outcomes are poor and heterogeneous. METHODS: ESCC-associated miRNAs were identified by microarray and validated by quantitative real-time polymerase chain reaction analyses in ESCC and normal esophageal epithelial samples. A multi-miRNA based classifier was established using a least absolute shrinkage and selection operator model in a training set of 145 LN-positive locoregional ESCCs, and further assessed in internal testing and independent validation sets of 145 and 243 patients, respectively. RESULTS: Twenty ESCC-associated miRNAs were identified and validated. A 4-miRNA based classifier (miR-135b-5p, miR-139-5p, miR-29c-5p, and miR-338-3p) was generated to classify LN-positive locoregional ESCC patients into high and low-risk groups. Patients with high-risk scores in the training set had a lower 5-year overall survival rate [8.7%, 95% confidence interval (CI): 0-20.3] than those with low-risk scores (50.3%, 95% CI: 40.0-60.7; P < 0.0001). The prognostic accuracy of the classifier was validated in the internal testing (P < 0.0001) and independent validation sets (P = 0.00073). Multivariate survival analyses showed that the 4-miRNA based classifier was an independent prognostic factor, and the combination of the 4-miRNA based classifier and clinicopathological prognostic factors significantly improved the prognostic accuracy of clinicopathological prognostic factors alone. CONCLUSION: Our 4-miRNA based classifier is a reliable prognostic prediction tool for overall survival in LN-positive locoregional ESCC patients and might offer a novel probability of ESCC treatment individualization.


Assuntos
Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/cirurgia , MicroRNAs/genética , Idoso , Biomarcadores Tumorais/genética , China , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
10.
Small ; 17(46): e2103091, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34643034

RESUMO

Hydrogel electrolytes have attracted enormous attention in flexible and safe supercapacitors. However, the interfacial contact problem between hydrogel electrolyte and electrodes, and the environmental instability are the key factors restricting the development of hydrogel-based supercapacitors. Here, a nucleotide-tackified adhesive organohydrogel electrolyte is successfully constructed and exhibits freezing resistance and water-holding ability based on the water/glycerol binary solvent system. Adenosine monophosphate enables the organohydrogels to possess outstanding adhesion and mechanical robustness. The robust adhesion can ensure close contact between the organohydrogel electrolyte and electrodes for constructing an all-in-one supercapacitor with low interfacial contact resistance. Impressively, the integrated organohydrogel-based supercapacitors display an areal specific capacitance of 163.6 mF cm-2 . Besides, the supercapacitors feature prominent environmental stability with capacitance retention of 90.6% after 5000 charging/discharging cycles at -20 °C. Furthermore, based on the strong interfacial adhesion, the supercapacitors present excellent electrochemical stability without delamination/displacement between electrolyte and electrodes even under severe deformations such as bending and twisting. It is anticipated that this work will provide an encouraging way for developing flexible energy storage devices with electrochemical stability and environmental adaptability.


Assuntos
Eletrólitos , Nucleotídeos , Capacitância Elétrica , Eletrodos , Hidrogéis
11.
Clin Exp Pharmacol Physiol ; 48(12): 1613-1620, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34343357

RESUMO

Cerebral vasospasm (CVS) is a frequent and serious neurosurgical complication, without sufficient therapy. This retrospective study was performed to analyze if nimodipine can improve prognosis and reduce ischaemia secondary to delayed CVS after intracranial tumour surgery. A retrospective review was performed over the years 2011 to 2012 for patients with an anterior cranial fossa tumour and underwent intracranial tumour surgery. The surgical field was soaked with nimodipine solution or normal saline. Transcranial Doppler ultrasonography was used to measure velocity in the middle cerebral artery (MCA) and the distal extracranial internal carotid artery (eICA). Follow-up was performed using the Glasgow Outcome Scale (GOS) after discharge. There were 94 patients that met the inclusion criteria. They included 50 males and 44 females, with a mean age of 49.6 years. In the nimodipine group, CVS occurred in 13 patients; 9 patients had CVS between 4 and 7 days, and 4 had CVS between 8 and 14 days. In the normal saline group, 19 patients had CVS, 3 presented with CVS within 3 days, 11 between 4-7 days and 5 between 8-14 days. A significant difference in the occurrence of CVS was observed between the two groups. Preoperative and postoperative the MCA velocities were compared, revealing a significant change in the normal saline group but not in the nimodipine group. Nimodipine markedly improves prognosis and significantly reduces ischaemia secondary to delayed CVS after intracranial tumour surgery, as well as the risks of mortality and morbidity.


Assuntos
Nimodipina
12.
Angew Chem Int Ed Engl ; 60(50): 26087-26095, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34490693

RESUMO

Synthetic molecular robots can execute sophisticated molecular tasks at nanometer resolution. However, a molecular robot capable of controlling cellular behavior remains unexplored. Herein, we report a self-propelled DNA robot operating on the cell membrane to control the migration of a cell. Driven by DNAzyme catalytic activity, the DNA robot could autonomously and stepwise move on the membrane-floating cell-surface receptors in a stochastic manner and simultaneously trigger the receptor-dimerization to activate downstream signaling for cell motility. The cell membrane-associated continuous motion and operation of a DNA robot allowed for the ultrasensitive regulation of MET/AKT signaling and cytoskeleton remodeling to enhance cell migration. Finally, we designed distinct conditional DNA robots to orthogonally manipulate the cell migration in a coculture of mixed cell populations. We have developed a novel strategy to engineer a cell-driving molecular robot, representing a promising avenue for precise cell manipulation with nanoscale resolution.


Assuntos
Membrana Celular/metabolismo , DNA Catalítico/metabolismo , DNA/metabolismo , Células A549 , Membrana Celular/química , Movimento Celular , DNA/química , Humanos
13.
J Cell Sci ; 131(8)2018 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-29567855

RESUMO

Stress granules are transient cytoplasmic foci induced by various stresses that contain translation-stalled mRNAs and RNA-binding proteins. They are proposed to modulate mRNA translation and stress responses. Here, we show that the deubiquitylases USP5 and USP13 are recruited to heat-induced stress granules. Heat-induced stress granules also contained K48- and K63-linked ubiquitin chains. Depletion of USP5 or USP13 resulted in elevated ubiquitin chain levels and accelerated assembly of heat-induced stress granules, suggesting that these enzymes regulate the stability of the stress granules through their ubiquitin isopeptidase activity. Moreover, disassembly of heat-induced stress granules after returning the cells to normal temperatures was markedly repressed by individual depletion of USP5 or USP13. Finally, overexpression of a ubiquitin mutant lacking the C-terminal diglycine motif caused the accumulation of unanchored ubiquitin chains and the repression of the disassembly of heat-induced stress granules. As unanchored ubiquitin chains are preferred substrates for USP5, we suggest that USP5 regulates the assembly and disassembly of heat-induced stress granules by mediating the hydrolysis of unanchored ubiquitin chains while USP13 regulates stress granules through deubiquitylating protein-conjugated ubiquitin chains.This article has an associated First Person interview with the first author of the paper.


Assuntos
Endopeptidases/metabolismo , Humanos , Hidrólise , Ligação Proteica , Proteases Específicas de Ubiquitina , Ubiquitinação
14.
Anal Chem ; 92(24): 16314-16321, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33259185

RESUMO

Proteases play crucial roles in the malignant progression of tumor and thus have been regarded as biomarkers for many cancers. Although protease assays such as immunoassays and fluorogenic substrate probes have been developed, it remains challenging for them to give consideration to both sensitivity and accuracy. Here, we describe a proteolysis-responsive rolling circle transcription assay (PRCTA) for the ultrasensitive and accurate detection of protease activities by the rational integration of a protease-responsive RNA polymerase and rolling circle transcription. Taking cancer biomarker matrix metalloproteinase-2 (MMP-2) as the model, the PRCTA, which can transduce and amplify each proteolysis event catalyzed by MMP-2 into the output of multiple tandem fluorescent RNAs by in vitro transcription, is constructed for the sensitive analysis of MMP-2 activities. Such a rational integration greatly enhances the signal gain in PRCTA, and it enables the limit of detection of MMP-2 as low as 3 fM. The feasibility of PRCTA has been validated by the sensitive analysis of cellular MMP-2 activities of different cell lines with good accuracy, and the readout can be readily visualized by a fluorescence imaging system. Therefore, PRCTA has achieved the detection of target protease biomarkers with femtomolar sensitivity, exhibiting promising potential in biomedicine research and cancer diagnosis.


Assuntos
Limite de Detecção , Metaloproteinase 2 da Matriz/metabolismo , Técnicas de Amplificação de Ácido Nucleico/métodos , Proteólise , Biomarcadores/metabolismo , Humanos
15.
Anal Chem ; 92(22): 15194-15201, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33136382

RESUMO

Neurotransmitters are essential chemical mediators for neuronal communication in variable neuromodulations. However, the progress of neuroscience is hampered by the shortage of suitable sensors to track neurotransmitters with high spatial and temporal resolution. Here, we introduce a self-assembled DNA-nanoprism fluorescent probe capable of nongenetically engineering the cell surface for ultrasensitive imaging of the neurotransmitter release at a single live-cell level. The DNA-nanoprism structure conjugated with three cholesterol tails enables the probe to rapidly and stably anchor on the cell surface within 10 min. The in situ detection of neurotransmitters is achieved by equipping the DNA-nanoprism with an aptamer-based "turn-on" fluorescent sensory module for the transmitter of interest. In a proof-of-concept study, we directly visualized the transient dopamine (DA) release on the cell surface with selective responsivity and high spatiotemporal precision and further explored the dynamic correlation between DA release and calcium influx triggered by high K+. This study provides a robust and sensitive tool for cell-surface-targeted imaging of neuromodulations, which might open up a new avenue to improve the understanding of neurochemistry and advance neuroscience research.


Assuntos
DNA/química , Corantes Fluorescentes/química , Nanoestruturas/química , Neurotransmissores/química , Neurotransmissores/metabolismo , Imagem Óptica/métodos , Linhagem Celular Tumoral , Sobrevivência Celular , Dopamina/metabolismo , Humanos , Neurônios/citologia
16.
Sensors (Basel) ; 21(1)2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33379408

RESUMO

Bandwidth is the crucial knowledge to sampling, reconstruction or estimation of the graph signal (GS). However, it is typically unknown in practice. In this paper, we focus on detecting the bandwidth of bandlimited GS with a small sample size, where the number of spectral components of GS to be tested may greatly exceed the sample size. To control the significance of the result, the detection procedure is implemented by multi-stage testing. In each stage, a Bayesian score test, which introduces a prior to the spectral components, is adopted to face the high dimensional challenge. By setting different priors in each stage, we make the test more powerful against alternatives that have similar bandwidth to the null hypothesis. We prove that the Bayesian score test is locally most powerful in expectation against the alternatives following the given prior. Finally, numerical analysis shows that our method has a good performance in bandwidth detection and is robust to the noise.

17.
Anal Chem ; 91(15): 9724-9731, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31283184

RESUMO

In the past decade, tandem mass spectrometry (MS/MS)-based bottom-up proteomics has become the method of choice for analyzing post-translational modifications (PTMs) in complex mixtures. The key to the identification of the PTM-containing peptides and localization of the PTM-modified residues is to measure the similarities between the theoretical spectra and the experimental ones. An accurate prediction of the theoretical MS/MS spectra of the modified peptides will improve the similarity measurement. Here, we proposed the deep-learning-based pDeep2 model for PTMs. We used the transfer learning technique to train pDeep2, facilitating the training with a limited scale of benchmark PTM data. Using the public synthetic PTM data sets, including the synthetic phosphopeptides and 21 synthetic PTMs from ProteomeTools, we showed that the model trained by transfer learning was accurate (>80% Pearson correlation coefficients were higher than 0.9), and was significantly better than the models trained without transfer learning. We also showed that accurate prediction of the fragment ion intensities of the PTM neutral loss, for example, the phosphoric acid loss (-98 Da) of the phosphopeptide, will improve the discriminating power to distinguish the true phosphorylated residue from its adjacent candidate sites. pDeep2 is available at https://github.com/pFindStudio/pDeep/tree/master/pDeep2 .

18.
Biomacromolecules ; 20(9): 3340-3351, 2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31356057

RESUMO

Thermoresponsive hydrogels are used for an array of biomedical applications. Lower critical solution temperature-type hydrogels have been observed in nature and extensively studied in comparison to upper critical solution temperature (UCST)-type hydrogels. Of the limited protein-based UCST-type hydrogels reported, none have been composed of a single coiled-coil domain. Here, we describe a biosynthesized homopentameric coiled-coil protein capable of demonstrating a UCST. Microscopy and structural analysis reveal that the hydrogel is stabilized by molecular entanglement of protein nanofibers, creating a porous matrix capable of binding the small hydrophobic molecule, curcumin. Curcumin binding increases the α-helical structure, fiber entanglement, mechanical integrity, and thermostability, resulting in sustained drug release at physiological temperature. This work provides the first example of a thermoresponsive hydrogel comprised of a single coiled-coil protein domain that can be used as a vehicle for sustained release and, by demonstrating UCST-type behavior, shows promise in forging a relationship between coiled-coil protein-phase behavior and that of synthetic polymer systems.


Assuntos
Portadores de Fármacos/química , Hidrogéis/química , Polímeros/química , Proteínas/química , Preparações de Ação Retardada/química , Portadores de Fármacos/síntese química , Hidrogéis/síntese química , Interações Hidrofóbicas e Hidrofílicas , Domínios Proteicos/genética , Engenharia de Proteínas , Temperatura
19.
Pharmacol Res ; 146: 104318, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31228552

RESUMO

Si-Miao-Yong-An decoction (SMYAD), a Chinese herbal formula, has been used in treating ischemic cardiovascular diseases. However, the cardioprotective mechanism of SMYAD treating heart failure (HF) remains unclear. Herein we investigated the effect of SMYAD on isoprenaline (ISO)-induced HF in C57BL/6 mice. Cardiac function and pathological changes in myocardial tissue were evaluated as well as A-type natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression. The underlying mechanism of SMYAD was deciphered using UHPLC MS/MS coupled with bioinformatics and was verified. SMYAD treatment significantly ameliorated cardiac function, reduced collagen deposition and cardiomyocyte apoptosis, reversed cardiac hypertrophy and down-regulated the expression levels of ANP and BNP mRNA compared with those in HF mice. Decipherment analyses based on 138 ingredients prompted that anti-oxidation was the key mechanism of SMYAD treating HF. In vitro and in vivo, SMYAD showed antioxidant activity, significantly up-regulated superoxide dismutase (SOD)-1 and SOD-2 mRNA expression levels and reduced NADP/NADPH ratio. Moreover, the increased expression levels of NADPH oxidase 2 (NOX2), p47phox and Rac family small GTPase 1 (Rac1) were obviously ameliorated after SMYAD treatment. Together, this study reveals that SMYAD can apparently improve heart function of ISO-induced HF mice by inhibiting the myocardial oxidative stress through restoring the equilibrium of SOD and NOX2.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Coração/efeitos dos fármacos , NADPH Oxidase 2/metabolismo , Superóxido Dismutase/metabolismo , Animais , Insuficiência Cardíaca/metabolismo , Isoproterenol/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Peptídeo Natriurético Encefálico , Estresse Oxidativo/efeitos dos fármacos
20.
Int J Hyperthermia ; 36(1): 21-28, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30428744

RESUMO

PURPOSE: We investigated the risk factors influencing MR changes associated with sacral injury from ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for uterine fibroids. METHODS: We retrospectively analyzed a total of 346 patients with symptomatic uterine fibroids who received USgHIFU ablation. All of the patients underwent contrast-enhanced magnetic resonance imaging (CE-MRI) before and after treatment. Injury to the sacrum was set as the dependent variable, while fibroid features and the treatment parameters were set as independent variables. These variables were used to assess respectively their correlation with sacral injury by using univariate and multivariate analyses. RESULTS: The results of univariate analysis revealed that the volume, distance from the fibroid to the skin, maximal diameter, distance from the fibroid to the sacrum, fibroid types, degree of enhancement, therapeutic dosimetry (TD), energy efficiency factor (EEF) and non-perfused volume (NPV) ratio manifested significant correlations with the sacral injury (p < .05). Multivariate analysis showed that the degree of enhancement, TD and EEF were independent risk factors for sacral injury (p < .05), while the distance from fibroid to sacrum and intramural or subserosal types were protective factors (p < .05). The incidence of sacral tail pain and leg pain showed a significant positive correlation with sacral injury (p < .05). CONCLUSION: As important affecting factors, the degree of enhancement, distance from fibroid to sacrum and fibroid types all possess significant correlations with MR changes associated with sacral injury.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Leiomioma/complicações , Leiomioma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Sacro/diagnóstico por imagem , Sacro/fisiopatologia , Adulto , Feminino , Humanos , Leiomioma/patologia , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA