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1.
Exp Neurol ; 377: 114805, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38729552

RESUMEN

Staufen-1 (STAU1) is a double-stranded RNA-binding protein (RBP) involved in a variety of pathological conditions. In this study, we investigated the potential role of STAU1 in Alzheimer's disease (AD), in which two hallmarks are well-established as cerebral ß-amyloid protein (Aß) deposition and Tau-centered neurofibrillary tangles. We found that STAU1 protein level was significantly increased in cells that stably express full-length APP and the brain of APP/PS1 mice, an animal model of AD. STAU1 knockdown, as opposed to overexpression, significantly decreased the protein levels of ß-amyloid converting enzyme 1 (BACE1) and Aß. We further found that STAU1 extended the half-life of the BACE1 mRNA through binding to the 3' untranslated region (3'UTR). Transcriptome analysis revealed that STAU1 enhanced the expression of growth arrest and DNA damage 45 ß (GADD45B) upstream of P38 MAPK signaling, which contributed to STAU1-induced regulation of Tau phosphorylation at Ser396 and Thr181. Together, STAU1 promoted amyloidogenesis by inhibiting BACE1 mRNA decay, and augmented Tau phosphorylation through activating GADD45B in relation to P38 MAPK. Targeting STAU1 that acts on both amyloidogenesis and tauopathy may serve as an optimistic approach for AD treatment.

2.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38729344

RESUMEN

INTRODUCTION: The CHA2DS2-VASc score, used to assess the risk of left atrial appendage thrombus (LAAT) formation in patients with atrial fibrillation (AF), has limited predictive value. Moreover, transesophageal echocardiography imaging, the gold standard diagnostic method to identify thrombi, is semi-invasive. Consequently, there is a need for alternative and noninvasive diagnostic methods for LAAT risk assessment. METHODS: Deep proteomic analysis was conducted in plasma samples from 8 patients with nonvalvular AF, divided into thrombus and control groups (4 patients in each group) based on the presence or absence of LAAT. Biomarkers associated with LAAT were validated using an enzyme-linked immunosorbent assay in a cohort of 179 patients with available clinical, transthoracic, and transesophageal echocardiography data. Predictive models were developed to assess the improvement in LAAT identification. RESULTS: The LAAT group had higher CHA2DS2-VASc scores, larger LA diameter, and lower LAA flow velocities. Deep proteomic analysis identified 30 differentially expressed proteins, including myosin light chain 4, prenylcysteine oxidase 1 (PCYOX1), and decorin as potential diagnostic biomarkers of LAAT. The model showed that PCYOX1 and decorin provided an area under the curve (AUC) of 0.970 for LAAT prediction compared with 0.672 in a model including the CHA2DS2-VASc score and LAA cauliflower morphology. The incremental value of proteomic biomarkers for LAAT in patients with nonvalvular AF was further confirmed with the net reclassification improvement and integrated discrimination improvement indices. CONCLUSIONS: Protein levels of PCYOX1 and decorin improve the predictive performance for LAAT in patients with nonvalvular AF.

4.
J Nanobiotechnology ; 22(1): 239, 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38735951

RESUMEN

Widespread distribution of porcine epidemic diarrhea virus (PEDV) has led to catastrophic losses to the global pig farming industry. As a result, there is an urgent need for rapid, sensitive and accurate tests for PEDV to enable timely and effective interventions. In the present study, we develop and validate a floating gate carbon nanotubes field-effect transistor (FG CNT-FET)-based portable immunosensor for rapid identification of PEDV in a sensitive and accurate manner. To improve the affinity, a unique PEDV spike protein-specific monoclonal antibody is prepared by purification, and subsequently modified on FG CNT-FET sensor to recognize PEDV. The developed FET biosensor enables highly sensitive detection (LoD: 8.1 fg/mL and 100.14 TCID50/mL for recombinant spike proteins and PEDV, respectively), as well as satisfactory specificity. Notably, an integrated portable platform consisting of a pluggable FG CNT-FET chip and a portable device can discriminate PEDV positive from negative samples and even identify PEDV and porcine deltacoronavirus within 1 min with 100% accuracy. The portable sensing platform offers the capability to quickly, sensitively and accurately identify PEDV, which further points to a possibility of point of care (POC) applications of large-scale surveillance in pig breeding facilities.


Asunto(s)
Técnicas Biosensibles , Nanotubos de Carbono , Virus de la Diarrea Epidémica Porcina , Virus de la Diarrea Epidémica Porcina/aislamiento & purificación , Animales , Porcinos , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Nanotubos de Carbono/química , Límite de Detección , Inmunoensayo/métodos , Inmunoensayo/instrumentación , Anticuerpos Monoclonales/inmunología , Transistores Electrónicos , Enfermedades de los Porcinos/diagnóstico , Enfermedades de los Porcinos/virología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/análisis , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/virología , Anticuerpos Antivirales/inmunología , Diseño de Equipo
5.
ACS Omega ; 9(17): 19236-19249, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38708219

RESUMEN

The aim of this study is to explore the inhibition of nanocalcium oxalate monohydrate (nano-COM) crystal adhesion and aggregation on the HK-2 cell surface after the protection of corn silk polysaccharides (CSPs) and the effect of carboxyl group (-COOH) content and polysaccharide concentration. METHOD: HK-2 cells were damaged by 100 nm COM crystals to build an injury model. The cells were protected by CSPs with -COOH contents of 3.92% (CSP0) and 16.38% (CCSP3), respectively. The changes in the biochemical indexes of HK-2 cells and the difference in adhesion amount and aggregation degree of nano-COM on the cell surface before and after CSP protection were detected. RESULTS: CSP0 and CCSP3 protection can obviously inhibit HK-2 cell damage caused by nano-COM crystals, restore cytoskeleton morphology, reduce intracellular ROS level, inhibit phosphoserine eversion, restore the polarity of the mitochondrial membrane potential, normalize the cell cycle process, and reduce the expression of adhesion molecules, OPN, Annexin A1, HSP90, HAS3, and CD44 on the cell surface. Finally, the adhesion and aggregation of nano-COM crystals on the cell surface were effectively inhibited. The carboxymethylated CSP3 exhibited a higher protective effect on cells than the original CSP0, and cell viability was further improved with the increase in polysaccharide concentration. CONCLUSIONS: CSPs can protect HK-2 cells from calcium oxalate crystal damage and effectively reduce the adhesion and aggregation of nano-COM crystals on the cell surface, which is conducive to inhibiting the formation of calcium oxalate kidney stones.

6.
Front Neurosci ; 18: 1396917, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38721047

RESUMEN

Background: Sleep plays a critical role in human physiological and psychological health, and electroencephalography (EEG), an effective sleep-monitoring method, is of great importance in revealing sleep characteristics and aiding the diagnosis of sleep disorders. Sleep spindles, which are a typical phenomenon in EEG, hold importance in sleep science. Methods: This paper proposes a novel convolutional neural network (CNN) model to classify sleep spindles. Transfer learning is employed to apply the model trained on the sleep spindles of healthy subjects to those of subjects with insomnia for classification. To analyze the effect of transfer learning, we discuss the classification results of both partially and fully transferred convolutional layers. Results: The classification accuracy for the healthy and insomnia subjects' spindles were 93.68% and 92.77%, respectively. During transfer learning, when transferring all convolutional layers, the classification accuracy for the insomnia subjects' spindles was 91.41% and transferring only the first four convolutional layers achieved a classification result of 92.80%. The experimental results demonstrate that the proposed CNN model can effectively classify sleep spindles. Furthermore, the features learned from the data of the normal subjects can be effectively applied to the data for subjects with insomnia, yielding desirable outcomes. Discussion: These outcomes underscore the efficacy of both the collected dataset and the proposed CNN model. The proposed model exhibits potential as a rapid and effective means to diagnose and treat sleep disorders, thereby improving the speed and quality of patient care.

7.
Angew Chem Int Ed Engl ; : e202406465, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38705847

RESUMEN

The surrounding hydrogen bond (H-bond) interaction around the active sites plays indispensable functions in enabling the organic electrode materials (OEMs) to fulfill their roles as ion reservoirs in aqueous zinc-organic batteries (ZOBs). Despite important, there are still no works could fully shed its real effects light on. Herein, quinone-based small molecules with a H-bond evolution model has been rationally selected to disclose the regulation and equilibration of H-bond interaction between OEMs, and OEM and the electrolyte. It has been found that only a suitable H-bond interaction could make the OEMs fully liberate their potential performance. Accordingly, the 2,5-diaminocyclohexa-2,5-diene-1,4-dione (DABQ) with elaborately designed H-bond structure exhibits a capacity of 193.3 mA h g-1 at a record-high mass loading of 66.2 mg cm-2 and 100% capacity retention after 1500 cycles at 5 A g-1. In addition, the DABQ//Zn battery also possesses air-rechargeable ability by utilizing the chemistry redox of proton. Our results put forward a specific pathway to precise utilization of H-bond to liberate the performance of OEMs.

8.
Food Chem ; 451: 139454, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38703725

RESUMEN

Morphology regulation of heterodimer nanoparticles and the use of their asymmetric features for further practical applications are crucial because of the rich optical properties and various combinations of heterodimers. This work used silicon to asymmetrically wrap half of a gold sphere and grew gold branches on the bare gold surface to form heterogeneous nano pineapples (NPPs) which can effectively improve Surface-enhanced Raman scattering (SERS) properties through chemical enhancement and lightning-rod effect respectively. The asymmetric structures of NPPs enabled them to self-assemble into the monolayer membrane with consistent branch orientation. The prepared substrate had high homogeneity and better SERS ability than disorganized substrates, and achieved reliable detection of malachite green (MG) in clams with a detection limit of 7.8 × 10-11 M. This work provided a guide to further revise the morphology of heterodimers and a new idea for the use of asymmetric dimers for practically photochemical and biomedical sensing.

9.
Neuroimage Clin ; 42: 103612, 2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38692208

RESUMEN

BACKGROUND: Subcortical stroke may significantly alter the cerebral cortical structure and affect attention function, but the details of this process remain unclear. The study aimed to investigate the neural substrates underlying attention impairment in patients with subcortical stroke. MATERIALS AND METHODS: In this prospective observational study, two distinct datasets were acquired to identify imaging biomarkers underlying attention deficit. The first dataset consisted of 86 patients with subcortical stroke, providing a cross-sectional perspective, whereas the second comprised 108 patients with stroke, offering longitudinal insights. All statistical analyses were subjected to false discovery rate correction upon P < 0.05. RESULTS: In the chronic-stage data, the stroke group exhibited significantly poorer attention function compared with that of the control group. The cortical structure analysis showed that patients with stroke exhibited decreased cortical thickness of the precentral gyrus and surface area of the cuneus, along with an increase in various frontal, occipital, and parietal cortices regions. The declined attention function positively correlated with the superior frontal gyrus cortical thickness and supramarginal gyrus surface area. In the longitudinal dataset, patients with stroke showed gradually increasing cortical thickness and surface area within regions of obvious structural reorganization. Furthermore, deficient attention positively correlated with supramarginal gyrus surface area both at the subacute and chronic stages post-stroke. CONCLUSIONS: Subcortical stroke can elicit dynamic reorganization of cortical areas associated with attention impairment. Moreover, the altered surface area of the supramarginal gyrus is a potential neuroimaging biomarker for attention deficits.

10.
Cancer Res Commun ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695555

RESUMEN

Mucosal melanoma exhibits limited responsiveness to anti-PD-1 therapy. However, a subgroup of mucosal melanomas, particularly those situated at specific anatomical sites like primary malignant melanoma of the esophagus (PMME), display remarkable sensitivity to anti-PD-1 treatment. The underlying mechanisms driving this superior response and the DNA methylation patterns in mucosal melanoma have not been thoroughly investigated. We collected tumor samples from 50 mucosal melanoma patients, including 31 PMME and 19 non-esophageal mucosal melanoma (NEMM). Targeted bisulfite sequencing was conducted to characterize the DNA methylation landscape of mucosal melanoma and explore the epigenetic profiling differences between PMME and NEMM. Bulk RNA sequencing and multiplex immunofluorescence staining were performed to confirm the impact of methylation on gene expression and immune microenvironment. Our analysis revealed distinct epigenetic signatures that distinguish mucosal melanomas of different origins. Notably, PMME exhibited distinct epigenetic profiling characterized by a global hypermethylation alteration compared to NEMM. The prognostic model based on the methylation scores of a 7-DMR panel could effectively predict the overall survival of PMME patients and potentially serve as a prognostic factor. PMME displayed a substantial enrichment of immune-activating cells in contrast to NEMM. Furthermore, we observed hypermethylation of the TERT promoter in PMME, which correlated with heightened CD8+ T cell infiltration, and patients with hypermethylated TERT were likely to have improved responses to immunotherapy. Our results indicated that PMME shows a distinct methylation landscape compared with NEMM, and the epigenetic status of TERT might be used to estimate prognosis and direct anti-PD-1 treatment for mucosal melanoma.

11.
Research (Wash D C) ; 7: 0353, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38694203

RESUMEN

Middle infrared stimulation (MIRS) and vibrational strong coupling (VSC) have been separately applied to physically regulate biological systems but scarcely compared with each other, especially at identical vibrational frequencies, though they both involve resonant mechanism. Taking cell proliferation and migration as typical cell-level models, herein, we comparatively studied the nonthermal bioeffects of MIRS and VSC with selecting the identical frequency (53.5 THz) of the carbonyl vibration. We found that both MIRS and VSC can notably increase the proliferation rate and migration capacity of fibroblasts. Transcriptome sequencing results reflected the differential expression of genes related to the corresponding cellular pathways. This work not only sheds light on the synergistic nonthermal bioeffects from the molecular level to the cell level but also provides new evidence and insights for modifying bioreactions, further applying MIRS and VSC to the future medicine of frequencies.

12.
Toxicol Res (Camb) ; 13(3): tfae072, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38737339

RESUMEN

Lead (Pb) is a nonessential heavy metal, which can cause many health problems. Isochlorogenic acid A (ICAA), a phenolic acid present in tea, fruits, vegetables, coffee, plant-based food products, and various medicinal plants, exerts multiple effects, including anti-oxidant, antiviral, anti-inflammatory and antifibrotic functions. Thus, the purpose of our study was to determine if ICAA could prevent Pb-induced hepatotoxicity in ICR mice. An evaluation was performed on oxidative stress, inflammation and fibrosis, and related signaling. The results indicate that ICAA attenuates Pb-induced abnormal liver function. ICAA reduced liver fibrosis, inflammation and oxidative stress caused by Pb. ICAA abated Pb-induced fibrosis and decreased inflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-alpha (TNF-α). ICAA abrogated reductions in activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Masson staining revealed that ICAA reduced collagen fiber deposition in Pb-induced fibrotic livers. Western blot and immunohistochemistry analyses showed ICAA increased phosphorylated AMP-activated protein kinase (p-AMPK) expression. ICAA also reduced the expression of collagen I, α-smooth muscle actin (α-SMA), phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated c-jun N-terminal kinase (p-JNK), p-p38, phosphorylated signal transducer and phosphorylated activator of transcription 3 (p-STAT3), transforming growth factor ß1 (TGF-ß1), and p-Smad2/3 in livers of mice. Overall, ICAA ameliorates Pb-induced hepatitis and fibrosis by inhibiting the AMPK/MAPKs/NF-κB and STAT3/TGF-ß1/Smad2/3 pathways.

13.
Lasers Surg Med ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38738401

RESUMEN

OBJECTIVES: The aim of this study is to investigate the safety and efficacy of excimer laser coronary angioplasty (ELCA) combined with drug-coated balloons (DCBs) in the treatment of in-stent restenosis (ISR), and to explore whether the contrast injection technique would improve the neointimal tissue ablation of ELCA. METHODS: We studied patients diagnosed with ISR between January 2019 and October 2022 at two medical centers. These patients underwent DCB angioplasty guided by optical coherence tomography (OCT). Based on whether ELCA was performed before DCB treatment, patients were categorized into two groups: the ELCA + DCB group and the DCB group. All patients underwent clinical follow-up 1 year after the procedure. The primary endpoint was the 1-year rate of target lesion revascularization (TLR), which was defined as any repeat percutaneous intervention or bypass surgery on the target vessel conducted to address restenosis or other complications related to the target lesion. The secondary endpoints including immediate luminal gain (ΔMLA, defined as the difference in minimum lumen area before and after the intervention). RESULTS: A total of 85 lesions in 75 patients were included. The mean age of the study population was 64.2 ± 12.0 years, with 81.3% male. Baseline clinical characteristics were well-balanced, and procedural success was 100% in both groups. The ELCA + DCB group (n = 24) exhibited a greater ΔMLA compared to the DCB group (n = 61) (3.57 ± 0.79 mm² vs. 2.50 ± 1.06 mm², [95% confidence interval, CI: 0.57-1.69], p < 0.001), The reduction in 1-year TLR was more frequently observed in patients from the ELCA + DCB group compared to the DCB group (hazard ratio 0.33 [95% CI: 0.11-0.99]; log-rank p = 0.048). The exploratory analysis showed that ELCA with contrast infusion is associated with greater acute lumen gain compared to ELCA with saline infusion (p < 0.001). CONCLUSIONS: The combination of ELCA and DCB is a safe and effective treatment strategy for in-stent stenosis. Additionally, compared with saline injection, ELCA with contrast injection is associated with greater acute lumen gain. However, the optimal contrast agent concentration and long-term outcome of the contrast injection technique need confirmation through larger sample sizes and prospective studies.

14.
Ther Adv Neurol Disord ; 17: 17562864241239117, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38616782

RESUMEN

Multiple sclerosis (MS) was defined as a rare disease in China due to its low prevalence. For a long time, interferon ß was the only approved disease-modifying therapy (DMT). Since the first oral DMT was approved in 2018, DMT approval accelerated, and seven DMTs were approved within 5 years. With an increasing number of DMTs being prescribed in clinical practice, it is necessary to discuss the standardized MS treatment algorithms depending on the disease activity and DMT availability. In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country.


Treatment algorithms of relapsing multiple sclerosis in China In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country: 1) CIS and RRMS account for more than 90% of the MS patients and most of them are mild to moderate; 2) MS patients should initiate DMT treatments as soon as the disease has been diagnosed in order to reduce the risk of disease progression; 3) Patients who have been diagnosed with MS should start treatment with fundamental DMTs unless the disease course has been highly active; 4) MAGNIMS score may be a suitable and simplified assessment tool for measuring treatment response to DMTs; 5) Patients treated with corticosteroids and NSIS should be switched to the standardized DMT treatment during remission in accordance with disease activity.

15.
Food Chem ; 449: 139246, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38604035

RESUMEN

The levels of metabolites in honey are influenced by floral origin, production region, and bee species. However, how environmental factors affect honey quality remains unclear. Based on untargeted metabolomics and using UPLC Q-Orbitrap MS, we analyzed 3596 metabolites in 51 honey samples from Yunnan and Shennongjia. Comparative analysis revealed that geniposidic acid, kynurenic acid and caffieine accumulated at significantly different levels between Shennongjia and Yunnan honey. Based on cluster structure analysis, 36 Yunnan honey samples were divided into two distinct groups by altitude. Notably, quercetin, hyperoside, taxifolin, rutin, tryptophan, astragalin and phenylalanine were higher levels in high-altitude honey (>1700 m), whereas abscisic acid was higher levels in low-altitude honey (≤1700 m). Among these, significantly elevated levels of hyperoside, taxfolin, astragalin, and tryptophan were observed in honey collected from high-altitude areas in Shennongjia. Our findings highlight the effect of altitude on honey health-promoting components, providing valuable insights into honey quality.


Asunto(s)
Altitud , Miel , Miel/análisis , Animales , Abejas/metabolismo , China , Metabolómica , Cromatografía Líquida de Alta Presión
16.
Plant Physiol Biochem ; 210: 108615, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38631158

RESUMEN

Magnesium is one of the essential nutrients for plant growth, and plays a pivotal role in plant development and metabolism. Soil magnesium deficiency is evident in citrus production, which ultimately leads to failure of normal plant growth and development, as well as decreased productivity. Citrus is mainly propagated by grafting, so it is necessary to fully understand the different regulatory mechanisms of rootstock and scion response to magnesium deficiency. Here, we characterized the differences in morphological alterations, physiological metabolism and differential gene expression between trifoliate orange rootstocks and lemon scions under normal and magnesium-deficient conditions, revealing the different responses of rootstocks and scions to magnesium deficiency. The transcriptomic data showed that differentially expressed genes were enriched in 14 and 4 metabolic pathways in leaves and roots, respectively, after magnesium deficiency treatment. And the magnesium transport-related genes MHX and MRS2 may respond to magnesium deficiency stress. In addition, magnesium deficiency may affect plant growth by affecting POD, SOD, and CAT enzyme activity, as well as altering the levels of hormones such as IAA, ABA, GA3, JA, and SA, and the expression of related responsive genes. In conclusion, our research suggests that the leaves of lemon grafted onto trifoliate orange were more significantly affected than the roots under magnesium-deficient conditions, further indicating that the metabolic imbalance of scion lemon leaves was more severe.


Asunto(s)
Citrus , Regulación de la Expresión Génica de las Plantas , Magnesio , Plantones , Citrus/metabolismo , Citrus/genética , Plantones/metabolismo , Plantones/genética , Plantones/crecimiento & desarrollo , Magnesio/metabolismo , Raíces de Plantas/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/genética , Deficiencia de Magnesio/metabolismo , Hojas de la Planta/metabolismo , Estrés Fisiológico , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética
17.
J Colloid Interface Sci ; 667: 119-127, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38631250

RESUMEN

The current state of drug delivery systems allows for the resolution of specific issues like inadequate solubility, limited targeting capabilities, and complex preparation processes, requiring tailored designs for different drugs. Yet, the major challenge in clinical application lies in surmounting these obstacles with a universal carrier that is effective for a variety of anticancer drugs. Herein, with the help of computer simulation, we rationally design ultrashort peptides GY and CCYRGD, which can co-assemble with hydrophobic anticancer drugs into nanoparticles with enhanced solubility, targeting ability and anticancer efficacy. Taking 7-ethyl-10-hydroxy camptothecin (SN38) as a model anticancer drug, the co-assembled SN38-GY-CCYRGD nanoparticles significantly enhance the water solubility of SN38 by more than three orders of magnitude. The as-prepared nanoparticles can effectively kill cancer cells, e.g., human small cell lung cancer (A549) cells with a notable cell mortality rate of 71%. Mice experimental results demonstrate the nanoparticles' efficient targeting capability, marked reducing the toxicity to normal tissues while improving antitumor efficacy. This work presents a novel drug delivery method, integrating effective, targeted, and safe strategies into a comprehensive carrier system, designed for the administration of hydrophobic anticancer drugs.


Asunto(s)
Antineoplásicos , Interacciones Hidrofóbicas e Hidrofílicas , Nanopartículas , Péptidos , Solubilidad , Humanos , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Ratones , Nanopartículas/química , Péptidos/química , Péptidos/farmacología , Irinotecán/farmacología , Irinotecán/química , Células A549 , Portadores de Fármacos/química , Supervivencia Celular/efectos de los fármacos , Tamaño de la Partícula , Sistemas de Liberación de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular/efectos de los fármacos , Ratones Endogámicos BALB C , Propiedades de Superficie , Camptotecina/química , Camptotecina/farmacología , Camptotecina/administración & dosificación
18.
Talanta ; 275: 126131, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38663064

RESUMEN

The development of an ultra-sensitive detection method for carbohydrate antigen 19-9 (CA19-9) is very important for the early diagnosis of pancreatic cancer. In this work, we developed a new strategy to achieve a variety of Au-Ag hybrid nanoparticles from janus to core-satellite which is controlled by the volume of AgNO3 and the concentration of benzimidazolecarboxylic acid (MBIA). With the volume of AgNO3 increased, Au-Ag hybrid nanoparticles changed from janus to core-satellite and the characteristic absorption peak showed two opposite trends. The size and number of Ag islands were determined by the concentration of MBIA. Au-Ag core-satellites nanoparticles with a large number of small-sized Ag have the highest SERS intensity. Then we used them as SERS nanotags and Au-Polystyrene nanospheres modified by captured anti-CA19-9 antibody as solid substrates to realize the ultra-sensitive detection of CA19-9 with a low limit of detection of 1.25 × 10-6 IU/mL and a wide linear range of 1.00 × 10-5 -1.00 × 104 IU/mL. This work not only demonstrates that MBIA and AgNO3 were the key factors in the growth of Au-Ag hybrid nanoparticles from 2D to 3D structure but also supplies an ultra-sensitive detection method for CA19-9 which has a potential practicability in the clinical early diagnoses of pancreatic cancer.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38651004

RESUMEN

Radiomics has been widely recognized for its effectiveness in decoding tumor phenotypes through the extraction of quantitative imaging features. However, the robustness of radiomic methods to estimate clinically relevant biomarkers non-invasively remains largely untested. In this study, we propose Cascaded Data Processing Network (CDPNet), a radiomic feature learning method to predict tumor molecular status from medical images. We apply CDPNet to an epigenetic case, specifically targeting the estimation of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation from Magnetic Resonance Imaging (MRI) scans of glioblastoma patients. CDPNet has three components: 1) Principal Component Analysis (PCA), 2) Fisher Linear Discriminant (FLD), and 3) a combination of hashing and blockwise histograms. The outlined architectural framework capitalizes on PCA to reconstruct input image patches, followed by FLD to extract discriminative filter banks, and finally using binary hashing and blockwise histogram module for indexing, pooling, and feature generation. To validate the effectiveness of CDPNet, we conducted an exhaustive evaluation on a comprehensive retrospective cohort comprising 484 IDH-wildtype glioblastoma patients with pre-operative multi-parametric MRI scans (T1, T1-Gd, T2, and T2-FLAIR). The prediction of MGMT promoter methylation status was cast as a binary classification problem. The developed model underwent rigorous training via 10-fold cross-validation on a discovery cohort of 446 patients. Subsequently, the model's performance was evaluated on a distinct and previously unseen replication cohort of 38 patients. Our method achieved an accuracy of 70.11% and an area under the curve of 0.71 (95% CI: 0.65 - 0.74).

20.
Medicine (Baltimore) ; 103(17): e37902, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38669415

RESUMEN

Cinnamon and motherwort are traditional Chinese medicines and are often combined to treat benign prostatic hyperplasia; however, the specific therapeutic mechanisms involved remain unclear. Therefore, in this study, we applied a network pharmacology approach to investigate the potential mechanisms of action of the drug pair cinnamon and motherwort (PCM) for the treatment of benign prostatic hyperplasia. Relevant targets for the use of PCM to treat benign prostatic hyperplasia were obtained through databases. Protein-protein interactions were then identified by the STRING database and core targets were screened. Enrichment analysis was conducted through the Metascape platform. Finally, molecular docking experiments were carried out to evaluate the affinity between the target proteins and ligands of PCM. We identified 22 active ingredients in PCM, 315 corresponding targets and 130 effective targets of PCM for the treatment of benign prostatic hyperplasia. These targets were related to the PI3K-Akt, MAPK, FoxO, TNF, and IL-17 signaling pathways. Network pharmacology was used to identify the effective components and action targets of PCM. We also identified potential mechanisms of action for PCM in the treatment of benign prostatic hyperplasia. Our results provide a foundation for expanding the clinical application of PCM and provide new ideas and directions for further research on the mechanisms of action of PCM and its components for the treatment of benign prostatic hyperplasia.


Asunto(s)
Cinnamomum zeylanicum , Simulación del Acoplamiento Molecular , Farmacología en Red , Hiperplasia Prostática , Hiperplasia Prostática/tratamiento farmacológico , Masculino , Humanos , Farmacología en Red/métodos , Cinnamomum zeylanicum/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Transducción de Señal/efectos de los fármacos , Medicina Tradicional China/métodos
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