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1.
Mikrochim Acta ; 191(9): 533, 2024 08 13.
Artículo en Inglés | MEDLINE | ID: mdl-39134753

RESUMEN

A novel functional nucleic acid (FNA) nanomaterial based on hybrid chain reaction (HCR) nanoscaffolds is proposed to solve the problem of time superposition and repeated primer design in sensitive miRND detection using cascade amplification technique. Rolling circle amplification (RCA) was cascaded with the prepared FNA nanomaterials for miRNA let-7a (as a model target) sensitive detection by lateral flow assay (LFA). Under the optimal conditions, the proposed RCA-FNA-LFA assay demonstrated the specificity and accuracy for miRNA let-7a detection with a detection limit of 1.07 pM, which increased sensitivity by nearly 20 times compared with that of RCA -LFA assay. It is worth noting that the non-target-dependent self-assembly process of HCR nanoscaffolds does not take up the whole detection time, thus, less time is taken than that of the conventional cascaded method. Moreover, the proposed assay does not need to consider the system compatibility between two kinds of isothermal amplification techniques. As for detection of different miRNAs, only the homologous arm of the padlock probe of RCA needs to be changed, while the FNA nanomaterial does not need any change, which greatly simplifies the primer design of the cascaded amplification techniques. With further development, the proposed RCA-FNA-LFA assay might achieve more sensitive and faster results to better satisfy the requirements of clinical diagnosis combing with more sensitive labels or small strip reader.


Asunto(s)
Límite de Detección , MicroARNs , Nanoestructuras , Técnicas de Amplificación de Ácido Nucleico , Técnicas de Amplificación de Ácido Nucleico/métodos , MicroARNs/análisis , Humanos , Nanoestructuras/química , Técnicas Biosensibles/métodos
2.
Biosens Bioelectron ; 264: 116656, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39133993

RESUMEN

Human space activities have been continuously increasing. Astronauts experiencing spaceflight are faced with health problems caused by special space environments such as microgravity, and the investigation of cell injury is fundamental. The development of a platform capable of cell culture and injury detection is the prerequisite for the investigation. Constructing a platform suitable for special conditions in space life science research is the key issue. The ground-based investigation is an indispensable part of the research. Accordingly, a simulated microgravity (SMG)-oriented integrated chip platform capable of 3D cell culture and in situ visual detection of superoxide anion radical (O2•-) is developed. SMG can cause oxidative stress in human cells, and O2•- is one of the signaling molecules. Thus, a O2•--responsive aggregation-induced emission (AIE) probe is designed, which shows high selectivity and sensitivity to O2•-. Moreover, the probe exhibits abilities of long-term and wash-free staining to cells due to the AIE behavior, which is precious for space cell imaging. Meanwhile, a chip with a high-aspect-ratio chamber for adequate medium storage for the lack of the perfusion system during the SMG experiment and a cell culture chamber which can integrate the extracellular matrix (ECM) hydrogel for the bioinspired 3D cell culture is fabricated. In addition, a porous membrane is introduced between the chambers to prevent the hydrogel from separating during the SMG experiment. The afforded AIE probe-ECM hydrogel-integrated chip can achieve 3D culturing of U87-MG cells and in situ fluorescent detection of endogenous O2•- in the cells after long-term staining under SMG. The chip provides a powerful and potential platform for ground-based investigation in space life science and biomedical research.


Asunto(s)
Técnicas Biosensibles , Hidrogeles , Superóxidos , Humanos , Superóxidos/análisis , Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Hidrogeles/química , Matriz Extracelular/química , Técnicas de Cultivo de Célula/instrumentación , Simulación de Ingravidez , Diseño de Equipo , Colorantes Fluorescentes/química , Dispositivos Laboratorio en un Chip , Ingravidez , Estrés Oxidativo
3.
Sensors (Basel) ; 24(16)2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39205054

RESUMEN

The practice of auscultation, interpreting body sounds to assess organ health, has greatly benefited from technological advancements in sensing and electronics. The advent of portable and wearable acoustic sensing devices marks a significant milestone in telemedicine, home health, and clinical diagnostics. This review summarises the contemporary advancements in acoustic sensing devices, categorized based on varied sensing principles, including capacitive, piezoelectric, and triboelectric mechanisms. Some representative acoustic sensing devices are introduced from the perspective of portability and wearability. Additionally, the characteristics of sound signals from different human organs and practical applications of acoustic sensing devices are exemplified. Challenges and prospective trends in portable and wearable acoustic sensors are also discussed, providing insights into future research directions.


Asunto(s)
Acústica , Dispositivos Electrónicos Vestibles , Humanos , Acústica/instrumentación , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , Telemedicina/instrumentación , Telemedicina/tendencias
4.
ACS Nano ; 18(35): 23876-23893, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39177073

RESUMEN

Fully integrated theranostic devices are highly esteemed in clinical applications, offering immense potential in real-time disease monitoring and personalized care. Microneedles (MNs), as innovative and wearable devices, boast important advantages in biosensing and therapy, thus holding significant promise in the advancement of diagnostic and therapeutic platforms. Encouragingly, advancements in electrochemical sensing technology, micronano fabrication, and biocompatible materials are propelling momentum for MNs-based closed-loop systems, enhancing detection capabilities, biocompatibility, and cost-effectiveness. Moreover, the notable progress in integrating MN chips with other biochips signifies a frontier for growth. Successful clinical trials in target molecule monitoring and drug delivery domains herald excellent clinical translational prospects for the aforementioned theranostic platform. Finally, we delineate both challenges and opportunities in the development of integrated diagnostic and therapeutic MN systems, including continuous monitoring, intelligent control algorithms, safety, and regulatory considerations.


Asunto(s)
Agujas , Nanomedicina Teranóstica , Humanos , Sistemas de Liberación de Medicamentos , Animales , Técnicas Biosensibles , Materiales Biocompatibles/química
6.
J Nat Med ; 78(4): 1013-1028, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39014275

RESUMEN

Inflammation-induced intestinal epithelial barrier (IEB) dysfunction is one of the important reasons for the occurrence and development of intestinal inflammatory-related diseases, including ulcerative colitis (UC), Crohn's disease and necrotizing enterocolitis (NEC). Dragon's blood (DB) is a traditional Chinese medicine and has been clinically used to treat UC. However, the protective mechanism of DB on intestinal inflammatory-related diseases has still not been elucidated. The present study aimed to explore the protection mechanism of DB on IEB dysfunction in rat ileum and human colorectal adenocarcinoma cells (Caco-2)/human umbilical vein endothelial cells (HUVECs) coculture system induced by lipopolysaccharide (LPS). DB could ameliorate rat ileum mucosa morphological injury, reduce the accumulation of lipid-peroxidation products and increase the expression of junction proteins. DB also alleviated LPS-induced Caco-2 cells barrier integrity destruction in Caco-2/ HUVECs coculture system, leading to increased trans-endothelial electrical resistance (TEER), reduced cell permeability, and upregulation of expressions of F-actin and junction proteins. DB contributed to the assembly of actin cytoskeleton by upregulating the FAK-DOCK180-Rac1-WAVE2-Arp3 pathway and contributed to the formation of intercellular junctions by downregulating TLR4-MyD88-NF-κB pathway, thus reversing LPS-induced IEB dysfunction. These novel findings illustrated the potential protective mechanism of DB on intestinal inflammatory-related diseases and might be useful for further clinical application of DB.


Asunto(s)
Mucosa Intestinal , Lipopolisacáridos , FN-kappa B , Transducción de Señal , Receptor Toll-Like 4 , Humanos , Células CACO-2 , Receptor Toll-Like 4/metabolismo , Animales , FN-kappa B/metabolismo , Lipopolisacáridos/farmacología , Lipopolisacáridos/toxicidad , Ratas , Transducción de Señal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Masculino , Regulación hacia Arriba/efectos de los fármacos , Ratas Sprague-Dawley
7.
FASEB J ; 38(14): e23831, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39037540

RESUMEN

Depression is a significant concern among astronauts, yet the molecular mechanisms underlying spaceflight-induced depression remain poorly understood. MicroRNAs (miRNAs) have emerged as potential regulators of neuropsychiatric disorders, including depression, but their specific role in space-induced depression remains unexplored. This study aimed to elucidate the involvement of candidate miRNAs (miR-455-3p, miR-206-3p, miR-132-3p, miR-16-5p, miR-124-3p, and miR-145-3p) and their interaction with differentially expressed genes (DEGs) in the neurobiology of spaceflight-induced depressive behavior. Using a simulated space environmental model (SCSE) for 21 days, depressive behavior was induced in rats, and candidate miRNA expressions and DEGs in the cortex region were analyzed through qRT-PCR and HPLC, respectively. Results showed that SCSE-exposed rats exhibited depressive behaviors, including anhedonia, increased immobility, and anxiousness compared to controls. Further analysis revealed increased hydrogen peroxide levels and decreased superoxide dismutase levels in the SCSE group, indicating abnormal oxidative stress in the cerebral cortex. Moreover, miRNA analysis demonstrated significant upregulation of miR-455-3p, miR-206-3p, miR-132-3p, and miR-16-5p expression. Among the DEGs identified, the in silico analysis highlighted their involvement in crucial pathways such as glutamatergic signaling, GABA synaptic pathway, and calcium signaling, implicating their role in spaceflight-induced depression. Protein-protein interaction analysis identified hub genes, including DLG4, DLG3, GRIN1, GRIN2B, GRIN2A, SYNGAP1, DLGAP1, GRIK2, and GRIN3A, impacting neuronal dysfunction functions in the cortex region of SCSE depressive rats. DLG4 emerged as a core gene regulated by miR-455-3p and miR-206-3p. Overall, this study underscores the potential of miRNAs as biomarkers for mood disorders and neurological abnormalities associated with spaceflight, advancing health sciences, and space health care.


Asunto(s)
Depresión , MicroARNs , Vuelo Espacial , Animales , MicroARNs/genética , MicroARNs/metabolismo , Ratas , Masculino , Depresión/metabolismo , Depresión/etiología , Depresión/genética , Ratas Sprague-Dawley , Modelos Animales de Enfermedad
8.
Artículo en Inglés | MEDLINE | ID: mdl-39083195

RESUMEN

Cascaded amplification showed promising potential for detection of trace target miRNAs in molecular diagnosis and prevention of many diseases. In this study, miRNA21 was chosen as the target, and rolling circle amplification (RCA)-based DNA nanoscaffold was integrated with target triggered RNA-cleaving DNAzyme for sensitive detection of miRNA21. That is, the H1 probe was bound with the long-chain product of RCA to self-assemble into DNA nanoscaffold. Target miRNA21 triggered the hybridization chain reaction (HCR) located on the nanoscaffold, and led to rapid proximity of DNAzyme fragments modified at both ends of the H2 probe, which realized the cyclic cleavage of self-quenching substrate probe efficiently, and the fluorescence signal was restored. The results demonstrated that the proposed assay was sensitive, 0.76 pM of miRNA21 can be detected. The proposed assay was specific; only one-base mismatched miRNA21 can be effectively recognized, other nucleic acid sequence and the serum matrix did not cause any interference. The proposed assay was accurate; recoveries from 82.1 to 115.0% can be obtained in the spiked fetal bovine serum (FBS). The flexible and programmable characteristics of DNA nanoscaffold and DNAzyme provide a confident and robust strategy for more sensitive nucleic acid detection, and can be developed to be a universal sensing platform for detecting other miRNAs just needing modification on the corresponding sequence of H1 probe in HCR.

9.
Langmuir ; 40(31): 16172-16179, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39042860

RESUMEN

Intestinal flora shows excellent affinity in the gut, and the adhesive property is borrowed for oral drug delivery. A facile strategy for bacteria engineering has been successfully developed by introducing metal-organic framework (MOF) mineralization. The MOF exoskeleton serves as an extendable platform for accommodating various cargoes with good Escherichia coli morphology maintained. The artificial exoskeleton surrounding E. coli is employed for encapsulating macromolecules as a therapeutic cargo, maintaining good bioactivity with high immobilization efficiency (60%) after systematic optimization of the MOF precursor. Leveraging the natural affinity of E. coli in the gut, the in-vivo tracking of MOF-engineered E. coli in the gastrointestinal tract confirmed excellent adhesion to the GI mucosa and a 17.9-fold increase in the gut retention half-time, demonstrating significant advantages in retention capability. In comparison, the control group without E. coli equipment resulted in quick gut passage. Furthermore, the artificially engineered E. coli serves as an effective carrier for macromolecules without notable oral toxicity, as evidenced by biocompatibility evaluations in cells and animals. Overall, the MOF-engineered E. coli provides an extendable platform for loading on-demand cargoes in versatile therapeutic functions with promising clinical transnationality for long-term applications.


Asunto(s)
Escherichia coli , Estructuras Metalorgánicas , Escherichia coli/efectos de los fármacos , Administración Oral , Animales , Estructuras Metalorgánicas/química , Humanos , Sistemas de Liberación de Medicamentos , Portadores de Fármacos/química
10.
Sci Data ; 11(1): 592, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38844753

RESUMEN

The 'Red Fuji' apple (Malus domestica), is one of the most important and popular economic crops worldwide in the fruit industry. Using PacBio HiFi long reads and Hi-C reads, we assembled a high-quality haplotype-resolved genome of 'Red Fuji', with sizes of 668.7 and 668.8 Mb, and N50 sizes of 34.1 and 31.4 Mb. About 97.2% of sequences were anchored in 34 chromosomes. We annotated both haploid genomes, identifying a total of 95,439 protein-coding genes in the two haplotype genomes, with 98% functional annotation. The haplotype-resolved genome of 'Red Fuji' apple stands as a precise benchmark for an array of analyses, such as comparative genomics, transcriptomics, and allelic expression studies. This comprehensive resource is paramount in unraveling variations in allelic expression, advancing quality improvements, and refining breeding efforts.


Asunto(s)
Genoma de Planta , Haplotipos , Malus , Malus/genética
11.
Mol Plant ; 17(8): 1221-1235, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38902921

RESUMEN

Xenia, the phenomenon in which the pollen genotype directly affects the phenotypic characteristics of maternal tissues (i.e., fruit ripening), has applications in crop production and breeding. However, the underlying molecular mechanism has yet to be elucidated. Here, we investigated whether mobile mRNAs from the pollen affect the ripening and quality-related characteristics of the fruit using cross-pollination between distinct Malus domestica (apple) cultivars. We demonstrated that hundreds of mobile mRNAs originating from the seeds are delivered to the fruit. We found that the movement of one of these mRNAs, ACC oxidase 3 (MdACO3), is coordinated with fruit ripening. Salicylic acid treatment, which can cause plasmodesmal closure, blocks MdACO3 movement, indicating that MdACO3 transcripts may move through the plasmodesmata. To assess the role of mobile MdACO3 transcripts in apple fruit, we created MdACO3-GFP-expressing apple seeds using MdACO3-GFP-overexpressing pollen for pollination and showed that MdACO3 transcripts in the transgenic seeds move to the flesh, where they promote fruit ripening. Furthermore, we demonstrated that MdACO3 can be transported from the seeds to fruit in the fleshy-fruited species tomato and strawberry. These results underscore the potential of mobile mRNAs from seeds to influence fruit characteristics, providing an explanation for the xenia phenomenon. Notably, our findings highlight the feasibility of leveraging diverse pollen genomic resources, without resorting to genome editing, to improve fruit quality.


Asunto(s)
Aminoácido Oxidorreductasas , Frutas , Malus , ARN Mensajero , Semillas , Semillas/genética , Semillas/crecimiento & desarrollo , Semillas/metabolismo , Malus/genética , Malus/crecimiento & desarrollo , Malus/metabolismo , Malus/enzimología , Frutas/genética , Frutas/crecimiento & desarrollo , Frutas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Aminoácido Oxidorreductasas/genética , Aminoácido Oxidorreductasas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Polinización
12.
ACS Nano ; 18(22): 14207-14217, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38767706

RESUMEN

Abnormal secretion and dysrhythmias of cortisol (CORT) are associated with various diseases such as sleep disorders, depression, and chronic fatigue. Wearable devices are a cutting-edge technology for point-of-care detection and dynamic monitoring of CORT with inspiring convenience. Herein, we developed a minimally invasive skin-worn device with the advanced integration of both interstitial fluid (ISF) sampling and target molecule sensing for simultaneous detection of CORT via a microneedle-based sensor with high sensitivity, excellent efficiency, and outstanding reproducibility. In the microneedle patch, swellable hydrogel was employed as the adsorption matrix for ISF extraction. Meanwhile, europium metal-organic frameworks (Eu-MOF) wrapped in the matrix played a vital role in CORT recognition and quantitative analysis. The wearable and label-free Eu-MOF-loaded microneedle patch exhibited high sensitivity in CORT detection with the detection limit reaching 10-9 M and excellent selectivity. Molecular dynamics simulation-driven mechanism exploration revealed that the strong interface interaction promoted fluorescence quenching of Eu-MOF. Moreover, in vitro and in vivo investigation confirmed the feasibility and reliability of the sensing method, and excellent biocompatibility was validated. Overall, a sensitive approach based on the wearable Eu-MOF microneedle (MN) patch was established for the simultaneous detection of CORT via visible fluorescence quenching with exciting clinical-translational ability.


Asunto(s)
Hidrocortisona , Estructuras Metalorgánicas , Agujas , Dispositivos Electrónicos Vestibles , Estructuras Metalorgánicas/química , Humanos , Hidrocortisona/análisis , Animales , Europio/química , Técnicas Biosensibles/instrumentación , Ratones
13.
Anal Methods ; 16(20): 3249-3255, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38726641

RESUMEN

The past and present scenario of COVID-19 has revealed the necessity of simple point-of-care tests. When combined with the great advantages of amplification, lateral flow assay nucleic acid analysis represents a more sensitive molecular diagnostic technique compared to universal protein analysis. Room temperature operation, an enzyme-free nature, and in situ elongation make hybrid chain reaction amplification (HCR) a good candidate for amplified combined lateral flow assays (LFAs). Since dual modes of detection can not only satisfy different application scenarios, but also reduce the false-negative rate, in this paper, visual and fluorescent detection based on labelling with colloidal gold nanoparticles and fluorescence labelling were incorporated into a HCR integrated with a LFA. The detection assay was finished in 30 minutes. The linear relationship between the signal and the concentration of the characteristic segment in the COVID-19 ORF gene was demonstrated. The obtained detection limits of as low as 10 fM (6.02 × 103 copies per mL) and 1 fM (6.02 × 102 copies per mL), respectively, were comparable with those in the literature. The multi-site HCR amplification integrated with LFA of a 1053 bp nucleic acid chain was also preliminarily studied, and tri-site amplification was found to exhibit higher signal intensity than single-site amplification. This study provides a promising strategy for simple, sensitive, and wide-ranging detection of pathogenic bacteria.


Asunto(s)
COVID-19 , Técnicas de Amplificación de Ácido Nucleico , SARS-CoV-2 , SARS-CoV-2/genética , Humanos , COVID-19/diagnóstico , Técnicas de Amplificación de Ácido Nucleico/métodos , Límite de Detección , Técnicas de Diagnóstico Molecular/métodos , Prueba de Ácido Nucleico para COVID-19/métodos , Prueba de Ácido Nucleico para COVID-19/instrumentación , Nanopartículas del Metal/química , ARN Viral/análisis , ARN Viral/genética
14.
Sci Data ; 11(1): 552, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811578

RESUMEN

Malus hybrid 'SH6' (M. honanensis × M. domestica)is a commonly used apple interstock in China, known for its excellent dwarfing characteristics and cold tolerance. In this study, a combined strategy utilizing PacBio HiFi, Hi-C and parental resequencing data were employed to assemble two haploid genomes for 'SH6'. After chromosome anchoring, the final hapH genome size was 596.63 Mb, with a contig N50 of 34.38 Mb. The hapR genome was 649.37 Mb, with a contig N50 of 36.84 Mb. Further analysis predicted that repeated sequences made up 59.69% and 62.52% of the entire genome, respectively. Gene annotations revealed 45,435 genes for hapH and 48,261 genes for hapR. Combined with genomic synteny we suggest that the hapR genome originates from its maternal parent M. domestica cv. Ralls Janet, while the hapH genome comes from its paternal parent, M. honanensis. The assembled genome significantly contributes to the discovery of genes associated with apple dwarfing and the molecular mechanisms governing them.


Asunto(s)
Genoma de Planta , Malus , Malus/genética , Cromosomas de las Plantas/genética
15.
Cells ; 13(10)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38786088

RESUMEN

Cellular demise is a pivotal event in both developmental processes and disease states, with mitochondrial regulation playing an essential role. Traditionally, cell death was categorized into distinct types, considered to be linear and mutually exclusive pathways. However, the current understanding has evolved to recognize the complex and interconnected mechanisms of cell death, especially within apoptosis, pyroptosis, and necroptosis. Apoptosis, pyroptosis, and necroptosis are governed by intricate molecular pathways, with mitochondria acting as central decision-makers in steering cells towards either apoptosis or pyroptosis through various mediators. The choice between apoptosis and necroptosis is often determined by mitochondrial signaling and is orchestrated by specific proteins. The molecular dialogue and the regulatory influence of mitochondria within these cell death pathways are critical research areas. Comprehending the shared elements and the interplay between these death modalities is crucial for unraveling the complexities of cellular demise.


Asunto(s)
Muerte Celular , Mitocondrias , Transducción de Señal , Humanos , Mitocondrias/metabolismo , Animales , Apoptosis , Piroptosis , Necroptosis/genética
16.
J Cancer ; 15(10): 3010-3023, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38706909

RESUMEN

Given the heterogeneity of tumors, there is an urgent need for accurate prognostic parameters in prostate cancer (PCa) patients. Lipid metabolism (LM) reprogramming and oxidative stress (OS) play a vital role in the progression of PCa. In this work, we identified five LM-OS-related genes (including ACOX2, PPRAGC1A, PTGS1, PTGS2, and HAO1) associated with the biochemical recurrence (BCR) of PCa. Subsequently, a prognostic signature was established based on these five genes. Kaplan-Meier survival estimates, receiver operating characteristic curves, and relationship analysis between risk score and clinical characters were applied to measure the robustness of the signature in an external cohort. A nomogram of risk score combined with clinical characteristics was constructed for clinical application. Functional enrichment analysis suggested that the underlying mechanism related to the signature included the calcium signaling, lipid transport, and cell cycle signaling pathways. Furthermore, WEE1 inhibitor was identified as a potential agent related to the cell cycle for high-risk patients. The mRNA expression and the prognostic value of the five genes were determined, and ACOX2 was identified as the key gene related to the prognostic signature. The protein expression of ACOX2 was measured in a prostate tissue microarray through an immunohistochemistry assay, confirming the bioinformatics results. By constructing the ACOX2-overexpressing PCa cell lines PC-3 and 22Rv1, the biological function of PCa cells was investigated. The cell viability, colony formation, migration, and invasion ability of PCa cell lines overexpressing ACOX2 were hindered. Decreased cellular lipid content and elevated cellular ROS content were observed in ACOX2-overexpressing PCa cell lines with reduced G2/M phases. In conclusion, this work presents the first prognostic signature specifically focused on LM-OS for PCa. ACOX2 could serve as a favorable indicator for the BCR in PCa. Further experiments are required to identify the potential underlying mechanism.

17.
Int J Nanomedicine ; 19: 3957-3972, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38711614

RESUMEN

Purpose: Current treatment approaches for Prostate cancer (PCa) often come with debilitating side effects and limited therapeutic outcomes. There is urgent need for an alternative effective and safe treatment for PCa. Methods: We developed a nanoplatform to target prostate cancer cells based on graphdiyne (GDY) and a copper-based metal-organic framework (GDY-CuMOF), that carries the chemotherapy drug doxorubicin (DOX) for cancer treatment. Moreover, to provide GDY-CuMOF@DOX with homotypic targeting capability, we coated the PCa cell membrane (DU145 cell membrane, DCM) onto the surface of GDY-CuMOF@DOX, thus obtaining a biomimetic nanoplatform (DCM@GDY-CuMOF@DOX). The nanoplatform was characterized by using transmission electron microscope, atomic force microscope, X-ray diffraction, etc. Drug release behavior, antitumor effects in vivo and in vitro, and biosafety of the nanoplatform were evaluated. Results: We found that GDY-CuMOF exhibited a remarkable capability to load DOX mainly through π-conjugation and pore adsorption, and it responsively released DOX and generated Cu+ in the presence of glutathione (GSH). In vivo experiments demonstrated that this nanoplatform exhibits remarkable cell-killing efficiency by generating lethal reactive oxygen species (ROS) and mediating cuproptosis. In addition, DCM@GDY-CuMOF@DOX effectively suppresses tumor growth in vivo without causing any apparent side effects. Conclusion: The constructed DCM@GDY-CuMOF@DOX nanoplatform integrates tumor targeting, drug-responsive release and combination with cuproptosis and chemodynamic therapy, offering insights for further biomedical research on efficient PCa treatment.


Asunto(s)
Cobre , Doxorrubicina , Grafito , Estructuras Metalorgánicas , Neoplasias de la Próstata , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Doxorrubicina/farmacología , Doxorrubicina/química , Animales , Humanos , Línea Celular Tumoral , Cobre/química , Cobre/farmacología , Grafito/química , Grafito/farmacología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Ratones , Liberación de Fármacos , Especies Reactivas de Oxígeno/metabolismo , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Ratones Desnudos , Nanopartículas/química , Antineoplásicos/farmacología , Antineoplásicos/química , Portadores de Fármacos/química , Ensayos Antitumor por Modelo de Xenoinjerto
18.
J Asian Nat Prod Res ; 26(7): 858-864, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38572987

RESUMEN

A new triterpenoid saponin (1), along with five known compounds (2-6), was isolated from Bupleurum marginatum Wall. ex DC, of which compounds 2-4 were obtained for the first time from this plant. The structures were confirmed by the analysis of 1D, 2D NMR, and HR-ESIMS data, and comparison with previous spectral data. Anti-liver fibrotic activities of the isolates were determined as proliferation inhibition of LPS-induced activation of HSC-T6 in vitro.


Asunto(s)
Bupleurum , Saponinas , Triterpenos , Saponinas/farmacología , Saponinas/química , Saponinas/aislamiento & purificación , Bupleurum/química , Triterpenos/farmacología , Triterpenos/química , Triterpenos/aislamiento & purificación , Estructura Molecular , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Cirrosis Hepática/tratamiento farmacológico , Lipopolisacáridos/farmacología , Animales , Resonancia Magnética Nuclear Biomolecular
19.
Angew Chem Int Ed Engl ; 63(28): e202405971, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38661248

RESUMEN

Aqueous soluble and stable Cu(I) molecular catalysts featuring a catenane ligand composed of two dicationic, mutually repelling but mechanically interlocked macrocycles are reported. The ligand interlocking not only fine-tunes the coordination sphere and kinetically stabilizes the Cu(I) against air oxidation and disproportionation, but also buries the hydrophobic portions of the ligands and prevents their dissociation which are necessary for their good water solubility and a sustained activity. These catenane Cu(I) complexes can catalyze the oxidative C-C coupling of indoles and tetrahydroisoquinolines in water, using H2O2 as a green oxidant with a good substrate scope. The successful use of catenane ligands in exploiting aqueous Cu(I) catalysis thus highlights the many unexplored potential of mechanical bond as a design element for exploring transition metal catalysis under challenging conditions.

20.
Int Immunopharmacol ; 132: 112017, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38599101

RESUMEN

BACKGROUND: Establishment of a reliable prognostic model and identification of novel biomarkers are urgently needed to develop precise therapy strategies for clear cell renal cell carcinoma (ccRCC). Stress response stated T cells (Tstr) are a new T-cell subtype, which are related to poor disease stage and immunotherapy response in various cancers. METHODS: 10 machine-learning algorithms and their combinations were applied in this work. A stable Tstr-related score (TCs) was constructed to predict the outcomes and PD-1 blockade treatment response in ccRCC patients. A nomogram based on TCs for personalized prediction of patient prognosis was constructed. Functional enrichment analysis and TimiGP algorithm were used to explore the underlying role of Tstr in ccRCC. The key TCs-related gene was identified by comprehensive analysis, and the bioinformatics results were verified by immunohistochemistry using a tissue microarray. RESULTS: A robust TCs was constructed and validated in four independent cohorts. TCs accurately predicted the prognosis and PD-1 blockade treatment response in ccRCC patients. The novel nomogram was able to precisely predict the outcomes of ccRCC patients. The underlying biological process of Tstr was related to acute inflammatory response and acute-phase response. Mast cells were identified to be involved in the role of Tstr as a protective factor in ccRCC. TNFS13B was shown to be the key TCs-related gene, which was an independent predictor of unfavorable prognosis. The protein expression analysis of TNFSF13B was consistent with the mRNA analysis results. High expression of TNFSF13B was associated with poor response to PD-1 blockade treatment. CONCLUSIONS: This study provides a Tstr cell-related score for predicting outcomes and PD-1 blockade therapy response in ccRCC. Tstr cells may exert their pro-tumoral role in ccRCC, acting against mast cells, in the acute inflammatory tumor microenvironment. TNFSF13B could serve as a key biomarker related to TCs.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Aprendizaje Automático , Carcinoma de Células Renales/inmunología , Humanos , Neoplasias Renales/inmunología , Pronóstico , Masculino , Femenino , Nomogramas , Biomarcadores de Tumor/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/genética , Persona de Mediana Edad , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Linfocitos T/inmunología
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