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1.
PLoS One ; 19(4): e0298178, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635558

RESUMO

BACKGROUND: Chronic heart failure (CHF) poses a significant burden on both patients and their family caregivers (FCs), as it is associated with psychological distress and impaired quality of life (QOL). Acceptance and Commitment Therapy (ACT) supports QOL by focusing on value living and facilitates acceptance of psychological difficulties by cultivating psychological flexibility. A protocol is presented that evaluates the effectiveness of a dyad ACT-based intervention delivered via smartphone on QOL and other related health outcomes compared with CHF education only. METHODS: This is a single-center, two-armed, single-blinded (rater), randomized controlled trial (RCT). One hundred and sixty dyads of CHF patients and their primary FCs will be recruited from the Cardiology Department of a hospital in China. The dyads will be stratified block randomized to either the intervention group experiencing the ACT-based intervention or the control group receiving CHF education only. Both groups will meet two hours per week for four consecutive weeks in videoconferencing sessions over smartphone. The primary outcomes are the QOL of patients and their FCs. Secondary outcomes include psychological flexibility, psychological symptoms, self-care behavior, and other related outcomes. All outcomes will be measured by blinded outcome assessors at baseline, immediately post-intervention, and at the three-month follow-up. Multilevel modeling will be conducted to assess the effects of the intervention. DISCUSSION: This study is the first to adopt an ACT-based intervention for CHF patient-caregiver dyads delivered in groups via smartphone. If effective and feasible, the intervention strategy and deliverable approach could be incorporated into clinical policies and guidelines to support families with CHF without geographic and time constraints. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04917159. Registered on 08 June 2021.


Assuntos
Terapia de Aceitação e Compromisso , Insuficiência Cardíaca , Humanos , Cuidadores/psicologia , Qualidade de Vida , Insuficiência Cardíaca/terapia , Comunicação por Videoconferência , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
BMC Plant Biol ; 24(1): 326, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658809

RESUMO

BACKGROUND: Salt stress severely inhibits plant growth, and the WRKY family transcription factors play important roles in salt stress resistance. In this study, we aimed to characterize the role of tobacco (Nicotiana tabacum) NtWRKY65 transcription factor gene in salinity tolerance. RESULTS: This study characterized the role of tobacco (Nicotiana tabacum) NtWRKY65 transcription factor gene in salinity tolerance using four NtWRKY65 overexpression lines. NtWRKY65 is localized to the nucleus, has transactivation activity, and is upregulated by NaCl treatment. Salinity treatment resulted in the overexpressing transgenic tobacco lines generating significantly longer roots, with larger leaf area, higher fresh weight, and greater chlorophyll content than those of wild type (WT) plants. Moreover, the overexpressing lines showed elevated antioxidant enzyme activity, reduced malondialdehyde content, and leaf electrolyte leakage. In addition, the Na+ content significantly decreased, and the K+/Na+ ratio was increased in the NtWRKY65 overexpression lines compared to those in the WT. These results suggest that NtWRKY65 overexpression enhances salinity tolerance in transgenic plants. RNA-Seq analysis of the NtWRKY65 overexpressing and WT plants revealed that NtWRKY65 might regulate the expression of genes involved in the salt stress response, including cell wall component metabolism, osmotic stress response, cellular oxidant detoxification, protein phosphorylation, and the auxin signaling pathway. These results were consistent with the morphological and physiological data. These findings indicate that NtWRKY65 overexpression confers enhanced salinity tolerance. CONCLUSIONS: Our results indicated that NtWRKY65 is a critical regulator of salinity tolerance in tobacco plants.


Assuntos
Regulação da Expressão Gênica de Plantas , Tabaco , Proteínas de Plantas , Plantas Geneticamente Modificadas , Tolerância ao Sal , Fatores de Transcrição , Tabaco/genética , Tabaco/fisiologia , Tolerância ao Sal/genética , Plantas Geneticamente Modificadas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
3.
Oncol Lett ; 27(5): 221, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38586211

RESUMO

MicroRNAs (miRNAs) were previously demonstrated to be involved in the pathogenesis of non-small-cell lung cancer (NSCLC); however, the roles of certain miRNAs in NSCLC remain to be elucidated. The present study aimed to investigate the functions of screened miRNAs in NSCLC and the potential mechanisms. First, expression profiles of miRNAs were downloaded from the Gene Expression Omnibus (dataset no. GSE29248) and the differentially expressed miRNAs were analyzed by bioinformatics methods. Reverse transcription-quantitative PCR was used to validate the differential expression of miR-373 in clinical samples. The association between miR-373 expression levels and clinicopathological characteristics was also investigated. To further examine how miR-373 mediates the emergence of NSCLC, western blot, Cell Counting Kit-8, cell invasion and wound-healing assays, as well as apoptosis detection and a luciferase assay were used. The results indicated significant downregulation of miR-373 in NSCLC tissues and its low expression was closely associated with the degree of differentiation, clinical stage and tumor size, and was indicative of an unfavorable prognosis for patients with NSCLC. A functional study indicated that overexpression of miR-373 inhibited the proliferation, promoted apoptosis, and suppressed invasion and migration of NSCLC cells. Bioinformatics prediction and functional assays suggested that Grb-associated binding protein 2 (GAB2) was a direct target of miR-373. In addition, GAB2 was found to be significantly upregulated in NSCLC tissues, and clinically, miR-373 was negatively associated with GAB2. Furthermore, overexpression of GAB2 blocked the tumor suppressive effects of miR-373 on NSCLC cells. Mechanistically, miR-373 mimics were able to reduce the expression of GAB2 and subsequently decrease the phosphorylation level of AKT and mTOR protein. The present results indicate that miR-373 exerts its anti-tumor effects in NSCLC cells by targeting the GAB2/PI3K/AKT pathway, suggesting that miR-373 may be a potential therapeutic target in NSCLC.

4.
BMC Pulm Med ; 24(1): 167, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589850

RESUMO

BACKGROUND: Cyclin D1 (CCND1) plays a pivotal role in cancer susceptibility and the platinum-based chemotherapy response. This study aims to assess the relationship between a common polymorphism (rs9344 G > A) in CCND1 gene with cancer susceptibility, platinum-based chemotherapy response, toxicities and prognosis of patients with lung cancer. METHODS: This study involved 498 lung cancer patients and 213 healthy controls. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Unconditional logistical regression analysis and meta-analysis were performed to evaluate the associations. RESULTS: The lung adenocarcinoma risk was significantly higher in patients with AA than GG + GA genotype (adjusted OR = 1.755, 95%CI = 1.057-2.912, P = 0.030). CCND1 rs9344 was significantly correlated with platinum-based therapy response in patients receiving PP regimen (additive model: adjusted OR = 1.926, 95%CI = 1.029-3.605, P = 0.040; recessive model: adjusted OR = 11.340, 95%CI = 1.428-90.100, P = 0.022) and in the ADC subgroups (recessive model: adjusted OR = 3.345, 95%CI = 1.276-8.765, P = 0.014). Furthermore, an increased risk of overall toxicity was found in NSCLC patients (additive model: adjusted OR = 1.395, 95%CI = 1.025-1.897, P = 0.034; recessive model: adjusted OR = 1.852, 95%CI = 1.088-3.152, P = 0.023), especially ADC subgroups (additive model: adjusted OR = 1.547, 95%CI = 1.015-2.359, P = 0.043; recessive model: adjusted OR = 2.030, 95%CI = 1.017-4.052, P = 0.045). Additionally, CCND1 rs9344 was associated with an increased risk of gastrointestinal toxicity in non-smokers (recessive model: adjusted OR = 2.620, 95%CI = 1.083-6.336, P = 0.035). Non-significant differences were observed in the 5-year overall survival rate between CCND1 rs9344 genotypes. A meta-analysis of 5432 cases and 6452 control samples did not find a significant association between lung cancer risk and CCND1 rs9344 polymorphism. CONCLUSION: This study suggests that in the Chinese population, CCND1 rs9344 could potentially serve as a candidate biomarker for cancer susceptibility and treatment outcomes in specific subgroups of patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Ciclina D1/genética , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Genótipo , Predisposição Genética para Doença
5.
ACS Nano ; 18(14): 10324-10340, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38547369

RESUMO

A major challenge in using nanocarriers for intracellular drug delivery is their restricted capacity to escape from endosomes into the cytosol. Here, we significantly enhance the drug delivery efficiency by accurately predicting and regulating the transition pH (pH0) of peptides to modulate their endosomal escape capability. Moreover, by inverting the chirality of the peptide carriers, we could further enhance their ability to deliver nucleic acid drugs as well as antitumor drugs. The resulting peptide carriers exhibit versatility in transfecting various cell types with a high efficiency of up to 90% by using siRNA, pDNA, and mRNA. In vivo antitumor experiments demonstrate a tumor growth inhibition of 83.4% using the peptide. This research offers a potent method for the rapid development of peptide vectors with exceptional transfection efficiencies for diverse pathophysiological indications.


Assuntos
Sistemas de Liberação de Medicamentos , Endossomos , Preparações Farmacêuticas , Endossomos/metabolismo , Peptídeos/metabolismo , Concentração de Íons de Hidrogênio
6.
BMC Genomics ; 25(1): 320, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549066

RESUMO

BACKGROUND: Stigma exsertion is an essential agricultural trait that can promote cross-pollination to improve hybrid seed production efficiency. However, the molecular mechanism controlling stigma exsertion remains unknown. RESULTS: In this study, the Nicotiana tabacum cv. K326 and its two homonuclear-heteroplasmic lines, MSK326 (male-sterile) and MSK326SE (male-sterile and stigma exserted), were used to investigate the mechanism of tobacco stigma exsertion. A comparison of the flowers between the three lines showed that the stigma exsertion of MSK326SE was mainly due to corolla shortening. Therefore, the corollas of the three lines were sampled and presented for RNA-seq analysis, which found 338 candidate genes that may cause corolla shortening. These genes were equally expressed in K326 and MSK326, but differentially expressed in MSK326SE. Among these 338 genes, 15 were involved in hormone synthesis or signal transduction pathways. Consistently, the content of auxin, dihydrozeatin, gibberellin, and jasmonic acid was significantly decreased in the MSK326SE corolla, whereas abscisic acid levels were significantly increased. Additionally, seven genes involved in cell division, cell cycle, or cell expansion were identified. Protein-protein interaction network analysis identified 45 nodes and 79 protein interactions, and the largest module contained 20 nodes and 52 protein interactions, mainly involved in the hormone signal transduction and pathogen defensive pathways. Furthermore, a putative hub gene coding a serine/threonine-protein kinase was identified for the network. CONCLUSIONS: Our results suggest that hormones may play a key role in regulating tobacco stigma exsertion induced by corolla shortening.


Assuntos
Tabaco , Transcriptoma , Tabaco/genética , Revelação , Ácidos Indolacéticos/metabolismo , Hormônios/metabolismo , Flores/metabolismo
7.
Langmuir ; 40(13): 7060-7066, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38513212

RESUMO

Nanosheet arrays with stable signal output have become promising photoactive materials for photoelectrochemical (PEC) immunosensors. However, an essential concern is the facile recombination of carriers in one-component nanoarrays, which cannot be readily prevented, ultimately resulting in weak photocurrent signals. In this study, an immunosensor using gold nanoparticle-anchored BiOI/Bi2S3 nanosheet arrays (BiOI/Bi2S3/Au) as a signal converter was fabricated for sensitive detection of cardiac troponin I (cTnI). The ternary nanosheet arrays were prepared by a simple method in which Bi2S3 was well-coated on the BiOI surface by in situ growth, whereas the addition of Au further improved the photoelectric conversion efficiency and could link more antibodies. The three-dimensional (3D) ordered sheet-like network array structure and BiOI/Bi2S3/Au ternary nanosheet arrays showed stable and high photoelectric signal output and no significant difference in signals across different batches under visible light excitation. The fabricated immunosensor has a sensitive response to the target detection marker cTnI in a wide linear range of 500 fg/mL to 50 ng/mL, and the detection limit was 32 fg/mL, demonstrating good stability and selectivity. This work not only shows the great application potential of ternary heterojunction arrays in the field of PEC immunosensors but also provides a useful exploration for improving the stability of immunosensors.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Troponina I , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Ouro/química , Imunoensaio/métodos , Limite de Detecção , Troponina I/química , Troponina I/imunologia , Bismuto/química
8.
J Mol Cell Cardiol ; 189: 38-51, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38387723

RESUMO

Acute aortic dissection (AAD) progresses rapidly and is associated with high mortality; therefore, there remains an urgent need for pharmacological agents that can protect against AAD. Herein, we examined the therapeutic effects of cannabidiol (CBD) in AAD by establishing a suitable mouse model. In addition, we performed human AAD single-cell RNA sequencing and mouse AAD bulk RNA sequencing to elucidate the potential underlying mechanism of CBD. Pathological assays and in vitro studies were performed to verify the results of the bioinformatic analysis and explore the pharmacological function of CBD. In a ß-aminopropionitrile (BAPN)-induced AAD mouse model, CBD reduced AAD-associated morbidity and mortality, alleviated abnormal enlargement of the ascending aorta and aortic arch, and suppressed macrophage infiltration and vascular smooth muscle cell (VSMC) apoptosis. Bioinformatic analysis revealed that the pro-apoptotic gene PMAIP1 was highly expressed in human and mouse AAD samples, and CBD could inhibit Pmaip1 expression in AAD mice. Using human aortic VSMCs (HAVSMCs) co-cultured with M1 macrophages, we revealed that CBD alleviated HAVSMCs mitochondrial-dependent apoptosis by suppressing the BAPN-induced overexpression of PMAIP1 in M1 macrophages. PMAIP1 potentially mediates HAVSMCs apoptosis by regulating Bax and Bcl2 expression. Accordingly, CBD reduced AAD-associated morbidity and mortality and mitigated the progression of AAD in a mouse model. The CBD-induced effects were potentially mediated by suppressing macrophage infiltration and PMAIP1 (primarily expressed in macrophages)-induced VSMC apoptosis. Our findings offer novel insights into M1 macrophages and HAVSMCs interaction during AAD progression, highlighting the potential of CBD as a therapeutic candidate for AAD treatment.


Assuntos
Dissecção Aórtica , Canabidiol , Animais , Humanos , Camundongos , Aminopropionitrilo/farmacologia , Dissecção Aórtica/tratamento farmacológico , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Canabidiol/farmacologia , Canabidiol/metabolismo , Macrófagos/metabolismo , Músculo Liso Vascular/patologia
9.
J Transl Med ; 22(1): 88, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254188

RESUMO

BACKGROUND: Risk stratification and personalized care are crucial in managing osteosarcoma due to its complexity and heterogeneity. However, current prognostic prediction using clinical variables has limited accuracy. Thus, this study aimed to explore potential molecular biomarkers to improve prognostic assessment. METHODS: High-throughput inhibitor screening of 150 compounds with broad targeting properties was performed and indicated a direction towards super-enhancers (SEs). Bulk RNA-seq, scRNA-seq, and immunohistochemistry (IHC) were used to investigate SE-associated gene expression profiles in osteosarcoma cells and patient tissue specimens. Data of 212 osteosarcoma patients who received standard treatment were collected and randomized into training and validation groups for retrospective analysis. Prognostic signatures and nomograms for overall survival (OS) and lung metastasis-free survival (LMFS) were developed using Cox regression analyses. The discriminatory power, calibration, and clinical value of nomograms were evaluated. RESULTS: High-throughput inhibitor screening showed that SEs significantly contribute to the oncogenic transcriptional output in osteosarcoma. Based on this finding, focus was given to 10 SE-associated genes with distinct characteristics and potential oncogenic function. With multi-omics approaches, the hyperexpression of these genes was observed in tumor cell subclusters of patient specimens, which were consistently correlated with poor outcomes and rapid metastasis, and the majority of these identified SE-associated genes were confirmed as independent risk factors for poor outcomes. Two molecular signatures were then developed to predict survival and occurrence of lung metastasis: the SE-derived OS-signature (comprising LACTB, CEP55, SRSF3, TCF7L2, and FOXP1) and the SE-derived LMFS-signature (comprising SRSF3, TCF7L2, FOXP1, and APOLD1). Both signatures significantly improved prognostic accuracy beyond conventional clinical factors. CONCLUSIONS: Oncogenic transcription driven by SEs exhibit strong associations with osteosarcoma outcomes. The SE-derived signatures developed in this study hold promise as prognostic biomarkers for predicting OS and LMFS in patients undergoing standard treatments. Integrative prognostic models that combine conventional clinical factors with these SE-derived signatures demonstrate substantially improved accuracy, and have the potential to facilitate patient counseling and individualized management.


Assuntos
Neoplasias Ósseas , Neoplasias Pulmonares , Osteossarcoma , Humanos , Prognóstico , Estudos Retrospectivos , Osteossarcoma/genética , Neoplasias Pulmonares/genética , Neoplasias Ósseas/genética , Biomarcadores , beta-Lactamases , Proteínas de Membrana , Proteínas Mitocondriais , Proteínas Repressoras , Fatores de Transcrição Forkhead , Fatores de Processamento de Serina-Arginina
10.
Horm Metab Res ; 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38278145

RESUMO

The aim of the work was to systematically evaluate the efficacy and safety of Vandetanib in the treatment of advanced medullary thyroid carcinoma (MTC). MeSH entries to search for randomized controlled trials and clinical research literature on the application of Vandetanib in the treatment of medullary thyroid cancer from PubMed, Chinese national knowledge infrastructure (CNKI), and Web of Science databases since their establishment until March 2023 were used. In terms of efficacy, the analysis results showed that Vandetanib had a significantly higher objective response rate compared to the control group using placebo (OR=2.13, 95% CI: 1.38, 3.29). In terms of side effects, Vandetanib significantly increases the incidence of hypertension, rash, and diarrhea, and has statistical significance (p+<+0.05). Vandetanib has a better therapeutic effect on MTC, but it also increases the incidence of hypertension, rash, and diarrhea. Attention should be paid to the relief of side effects when using it.

11.
Circulation ; 149(14): 1121-1138, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38152931

RESUMO

BACKGROUND: Progressive remodeling of cardiac gene expression underlies decline in cardiac function, eventually leading to heart failure. However, the major determinants of transcriptional network switching from normal to failed hearts remain to be determined. METHODS: In this study, we integrated human samples, genetic mouse models, and genomic approaches, including bulk RNA sequencing, single-cell RNA sequencing, chromatin immunoprecipitation followed by high-throughput sequencing, and assay for transposase-accessible chromatin with high-throughput sequencing, to identify the role of chromatin remodeling complex INO80 in heart homeostasis and dysfunction. RESULTS: The INO80 chromatin remodeling complex was abundantly expressed in mature cardiomyocytes, and its expression further increased in mouse and human heart failure. Cardiomyocyte-specific overexpression of Ino80, its core catalytic subunit, induced heart failure within 4 days. Combining RNA sequencing, chromatin immunoprecipitation followed by high-throughput sequencing, and assay for transposase-accessible chromatin with high-throughput sequencing, we revealed INO80 overexpression-dependent reshaping of the nucleosomal landscape that remodeled a core set of transcription factors, most notably the MEF2 (Myocyte Enhancer Factor 2) family, whose target genes were closely associated with cardiac function. Conditional cardiomyocyte-specific deletion of Ino80 in an established mouse model of heart failure demonstrated remarkable preservation of cardiac function. CONCLUSIONS: In summary, our findings shed light on the INO80-dependent remodeling of the chromatin landscape and transcriptional networks as a major mechanism underlying cardiac dysfunction in heart failure, and suggest INO80 as a potential preventative or interventional target.


Assuntos
Redes Reguladoras de Genes , Insuficiência Cardíaca , Humanos , Animais , Camundongos , Montagem e Desmontagem da Cromatina , Cromatina/metabolismo , Miócitos Cardíacos/metabolismo , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , RNA/metabolismo , Transposases/metabolismo , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Proteínas de Ligação a DNA/metabolismo
12.
Sensors (Basel) ; 23(23)2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38067978

RESUMO

In this work, a flexible electrochemical sensor was developed for the detection of organophosphorus pesticides (OPs). To fabricate the sensor, graphene was generated in situ by laser-induced graphene (LIG) technology on a flexible substrate of polyimide (PI) film to form a three-electrode array, and pralidoxime (PAM) chloride was used as the probe molecule. CeO2 was used to modify the working electrode to improve the sensitivity of the sensor because of its electrocatalytic effect on the oxidation of PAM, and the Ag/AgCl reference electrode was prepared by the drop coating method. The effects of the laser power, laser scanning speed, and CeO2 modification on the electrochemical properties of the sensor were studied in detail. The results prove that the sensor has good repeatability, stability, and anti-interference ability, and it shows an excellent linear response in the chlorpyrifos concentration range from 1.4 × 10-8 M to 1.12 × 10-7 M with the detection limit of 7.01 × 10-10 M.

13.
Analyst ; 148(20): 5210-5220, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37724336

RESUMO

In this study, a simple and portable electrochemical sensor based on laser-induced graphene (LIG) has been developed to systematically investigate the feasibility of LIG as an electrode to detect organophosphorus pesticides (OPs). It proves that the LIG-based electrode has a relatively high electrochemically active surface area (ECSA) and heterogeneous electron transfer (HET) of 0.100 cm2 and 0.000825 cm s-1, respectively. In addition, zirconium dioxide nanoparticles (ZrO2 NPs) have been modified on the electrode with three different binders, ß-cyclodextrin (ß-CD), chitosan (CS) and Nafion, to improve the adsorption capacity of the electrode toward OPs, and the effect of the binders on the performance of the as-fabricated sensor has been investigated in detail. The results show that ß-CD increases not only the electrochemically active surface area of the electrode but also the redox peak current of methyl parathion (MP). To evaluate the sensitivity of the sensor, differential pulse voltammetry (DPV) curves have been tested in solutions containing different concentrations of MP using ZrO2-ß-CD/LIG as an electrode, which shows a detection range of 5-200 ng ml-1 and a detection limit of 0.89 ng ml-1. In summary, the LIG-based sensor has a low detection limit, high sensitivity and good interference resistance, and thus has tremendous potential for the detection of pesticides in the environment.

14.
J Mater Chem B ; 11(37): 8974-8984, 2023 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-37700728

RESUMO

The tumor microenvironment is a very complex and dynamic ecosystem. Although a variety of pH-responsive peptides have been reported to deliver nucleic acid drugs for cancer treatment, these responses typically only target the acidic microenvironment of the tumor or the lysosome, and the carrier suffers from issues such as low transfection efficiency and poor lysosomal escape within the cell. To address this problem, we have developed an ultra pH-responsive peptide nanocarrier that can efficiently deliver siRNA, pDNA, and mRNA into cancer cells by performing progressive dynamic assembly in response to pH changes in the acidic tumor microenvironment (pH 6.5-6.8) and the acidic intracellular lysosomal environment (pH 5.0-6.0). The maximum transfection efficiency was 87.1% for pDNA and 74.9% for mRNA, which is higher than that of peptide-based nanocarrier reported to date. In addition, the targeting sequence on the surface allows the peptide@siRNA complex to efficiently enter cancer cells, causing 96% of cancer cell mortality. The carrier has high biocompatibility and low cytotoxicity, making it highly promising for application in immunotherapy and gene therapy of tumors.


Assuntos
Neoplasias , Microambiente Tumoral , Genes Neoplásicos , Concentração de Íons de Hidrogênio , Neoplasias/tratamento farmacológico , Peptídeos , RNA Mensageiro , RNA Interferente Pequeno/farmacologia
15.
Sensors (Basel) ; 23(18)2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37765870

RESUMO

Denoising remote sensing images is crucial in the application and research of remote sensing imagery. Noise in remote sensing images originates from sensor characteristics, signal transmission, and environmental conditions, among which Gaussian noise is the most common type. In this paper, we proposed a multiple-optimization bilateral filtering (MOBF) algorithm based on edge detection and differential evolution (DE) methods. The proposed algorithm optimizes the spatial domain filtering kernel and the spatial domain Gaussian kernel by using the standard deviation and width of the edge response. By employing the DE algorithm, the individuals in the population based on the standard deviation of the gray value domain are subjected to iterative mutation, crossover, and selection operations to refine the latent solution vectors and determine the optimal color space for optimizing the standard deviation of the pixel range domain kernel. As a result, the MOBF algorithm, which does not require any parameter input, is realized. To verify the feasibility and effectiveness of the proposed algorithm, denoising experiments were conducted on remote sensing images by using evaluation metrics such as the mean squared error, peak signal-to-noise ratio, and structural similarity index. The experimental results revealed that the MOBF algorithm outperforms traditional algorithms for all three evaluation metrics.

16.
J Sport Rehabil ; 32(7): 818-826, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37527818

RESUMO

BACKGROUND: Low-intensity resistance exercise therapy (LIRET) based on myofascial chains, applied to both affected and nonlocal joints, is an effective method for knee osteoarthritis (OA) rehabilitation. This study applied LIRET in a comparison of prevalues and postvalues of lower-limb tension in female patients with knee OA and asymptomatic participants. METHODS: Twenty-four female participants with knee OA and 20 asymptomatic women took part in a 3-month long application of LIRET. Participants' ankle passive torque and ankle range of motion in the sagittal plane were assessed with an isokinetic dynamometer. The collected values were used to estimate the sagittal-plane lower-limb tension. RESULTS: Compared with the asymptomatic group, participants with knee OA presented decreased maximum ankle dorsiflexion (P < .001), decreased ankle plantar flexion range (P = .023), ankle resting position more inclined to dorsiflexion (P = .017), increased ankle dorsiflexion stiffness (P = .005), and lower ankle plantar flexion stiffness (P = .034). After exercise intervention, the knee OA group self-reported less knee pain (P < .001), improved physical function (P < .001), increased maximum dorsiflexion (P = .021), and increased plantar flexion range (P < .001). While plantar flexion stiffness increased (P = .037), dorsiflexion stiffness decreased (P = .015) and ankle resting position moved toward dorsiflexion (P = .002). Results suggest possible decreased anterior leg tension and possible increased posterior leg tension in patients with knee OA. CONCLUSIONS: The results supported that knee OA patients present imbalanced myofascial tension of lower limbs. LIRET based on myofascial chains appears to decrease pain, and stiffness, and improve physical function of patients with knee OA and change their lower-limb tension.


Assuntos
Osteoartrite do Joelho , Treinamento de Força , Humanos , Feminino , Osteoartrite do Joelho/terapia , Extremidade Inferior , Articulação do Tornozelo , Nível de Saúde , Amplitude de Movimento Articular , Exercício Físico
17.
J Xray Sci Technol ; 31(6): 1263-1280, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37599557

RESUMO

BACKGROUND: Preoperative prediction of cervical lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) is significant for surgical decision-making. OBJECTIVE: This study aims to develop a dual-modal radiomics (DMR) model based on grayscale ultrasound (GSUS) and dual-energy computed tomography (DECT) for non-invasive CLNM in PTC. METHODS: In this study, 348 patients with pathologically confirmed PTC at Jiangsu University Affiliated People's Hospital who completed preoperative ultrasound (US) and DECT examinations were enrolled and randomly assigned to training (n = 261) and test (n = 87) cohorts. The enrolled patients were divided into two groups based on pathology findings namely, CLNM (n = 179) and CLNM-Free (n = 169). Radiomics features were extracted from GSUS images (464 features) and DECT images (960 features), respectively. Pearson correlation coefficient (PCC) and the least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation were then used to select CLNM-related features. Based on the selected features, GSUS, DECT, and GSUS combined DECT radiomics models were constructed by using a Support Vector Machine (SVM) classifier. RESULTS: Three predictive models based on GSUS, DECT, and a combination of GSUS and DECT, yielded performance of areas under the curve (AUC) = 0.700 [95% confidence interval (CI), 0.662-0.706], 0.721 [95% CI, 0.683-0.727], and 0.760 [95% CI, 0.728-0.762] in the training dataset, and AUC = 0.643 [95% CI, 0.582-0.734], 0.680 [95% CI, 0.623-0.772], and 0.744 [95% CI, 0.686-0.784] in the test dataset, respectively. It shows that the predictive model combined GSUS and DECT outperforms both models using GSUS and DECT only. CONCLUSIONS: The newly developed combined radiomics model could more accurately predict CLNM in PTC patients and aid in better surgical planning.


Assuntos
Pescoço , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Pescoço/diagnóstico por imagem , Área Sob a Curva , Neoplasias da Glândula Tireoide/diagnóstico por imagem
18.
Chemphyschem ; 24(22): e202300211, 2023 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-37610324

RESUMO

As an exceptional Fenton-like reagent, cerium oxide (CeO2 ) finds applications in biomedical science and organic pollutants treatment. The Fenton-like reaction catalyzed by CeO2 typically encompasses two distinct processes: one resembling the classical Fenton reaction, wherein cerium (Ce3+ ) triggers the decomposition of hydrogen peroxide (H2 O2 ) to yield reactive oxygen species (ROS), and the other involves the complexation of H2 O2 on the Ce3+ surface, leading to the formation of peroxides. However, the influence of diverse CeO2 morphologies on these two reaction pathways has not been comprehensively explored. In this study, CeO2 exhibiting three typical morphologies, rods, cubes, and spheres, were prepared. The generation of ROS and peroxides was evaluated using the 3,3,5,5-tetramethylbenzidine (TMB) oxidation reaction and the reduction current of H2 O2 , respectively. Moreover, the impacts of pH variations and CeO2 /H2 O2 concentrations on the production and conversion of these two reaction products were investigated. To corroborate the distinctions between the resultant products and their applicability, apoptosis assays and acid orange 7 (AO7) degradation analyses were performed. Notably, CeO2 rods exhibited the highest proportion of Ce3+ , predominantly engaging in complexation with H2 O2 to foster peroxide formation, thereby facilitating the robust degradation of AO7. However, the generated peroxides appeared to occupy Ce3+ sites, thereby impeding the H2 O2 decomposition process. Conversely, Ce3+ species on the surface of CeO2 cubes were primarily involved in H2 O2 decomposition, leading to heightened ROS production, and thus showcasing substantial potential for damaging A549 tumor cells. It is worth noting that the ability of these Ce3+ species to form peroxides through complexation with H2 O2 was comparatively reduced. In summation, this study sheds light on the intricate interplay between distinct CeO2 morphologies and their divergent impacts on Fenton-like reactions. These findings expand our comprehension of the influences on its reactivity of CeO2 morphologies and open new insights for applications in diverse domains, from organic dye degradation to tumor therapy.


Assuntos
Cério , Peróxidos , Espécies Reativas de Oxigênio , Catálise , Cério/química
19.
J Colloid Interface Sci ; 652(Pt A): 518-528, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37607414

RESUMO

Inspired by ordered photonic crystals and structural color materials in nature, we successfully prepared hydroxypropyl cellulose (HPC) photonic films with ordered surface arrays by double-imprint soft lithography. Then we introduced another important material of the cellulose family, cellulose nanocrystals (CNC), which has liquid crystal nature and birefringent properties of the particles, into the system to realize the single-point shrinkage of the film array and the control of structural color. Through multi-component doping and concentration control, we further optimized the multi-scale structure of the materials, and obtained HPC/CNCs composite photonic films with excellent properties in color, stability and flexibility, whose elastic modulus and tensile properties are significantly higher than those of single-component. Further loading of SiO2@PDA enhances the color saturation and realizes the in-situ reduction of metal ions on the film surface. This plasma film can track a variety of substances with high sensitivity and long-term stability, showing potential application prospects in the field of surface-enhanced Raman scattering (SERS), which provides a potential possibility for chiral structures to be used in the field of biosensor detection and circularly polarized luminescence.

20.
Genomics ; 115(5): 110685, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37454936

RESUMO

Aortic dissection is a devastating cardiovascular disease with a high lethality. Histone variants maintain the genomic integrity and play important roles in development and diseases. However, the role of histone variants in aortic dissection has not been well identified. In the present study, H3f3b knockdown reduced the synthetic genes expression of VSMCs, while overexpressing H3f3b exacerbated the cellular immune response of VSMCs induced by inflammatory cytokines. Combined RNA-seq and ChIP-seq analyses revealed that histone variant H3.3B directly bound to the genes related to extracellular matrix, VSMC synthetic phenotype, cytokine responses and TGFß signaling pathway, and regulated their expressions. In addition, VSMC-specific H3f3b knockin aggravated aortic dissection development in mice, while H3f3b knockout significantly reduced the incidence of aortic dissection. In term of mechanisms, H3.3B regulated Spp1 and Ccl2 genes, inducing the apoptosis of VSMCs and recruiting macrophages. This study demonstrated the vital roles of H3.3B in phenotypic transition of VSMCs, loss of media VSMCs, and vascular inflammation in aortic dissection.


Assuntos
Dissecção Aórtica , Músculo Liso Vascular , Camundongos , Animais , Músculo Liso Vascular/metabolismo , Histonas/metabolismo , Dissecção Aórtica/genética , Fenótipo , Inflamação/genética , Miócitos de Músculo Liso/metabolismo , Células Cultivadas
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