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1.
Heliyon ; 10(7): e28450, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38560231

RESUMEN

Fermentation is an effective means of enhancing the nutritional value of natural medicines, however, it is unclear how the metabolites changed during the fermentation of Paeonia lactiflora root (PLR). This study intends to elucidate how the active constituents and antioxidant activity of PLR change during fermentation. The study examined the levels of total glucosides of paeony (TGP), total flavonoids content (TFC), total phenols content (TPC), and antioxidant capability by high performance liquid chromatography (HPLC) and spectrophotometry. The chemical compositions before and after PLR fermentation were compared utilizing ultra-high performance liquid chromatography-mass spectrometry (UHPLC - MS). The findings from this study indicate that TGP, TFC and TPC peaked at Day 2 of fermentation, and the antioxidant capacity increased after fermentation. Of the 109 detected compounds, 18 were discrepant compounds. In summary, fermentation is an essential strategy for enhancing the functional activity of PLR. The current study could establish a scientific basis for future research on the fermentation of PLR, and provides new insights into the influence of fermentation on chemical composition as well as the antioxidant activity of drugs.

2.
Asian J Pharm Sci ; 19(2): 100906, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38595333

RESUMEN

Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.

3.
Support Care Cancer ; 32(5): 300, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38644409

RESUMEN

PURPOSE: We evaluated the efficacy of megestrol in improving chemotherapy-related anorexia by analyzing the related scales of taste alteration. METHODS: We conducted the current study on a group of advanced patients with cancer with two or more chemotherapy cycles. The chemotherapy-induced taste alteration scale (CiTAs) scale helped assess the megestrol effects on basic taste perception, aversive taste changes, unpleasant symptoms, and associated concerns. Furthermore, the Short Nutritional Assessment Questionnaire scale (SNAQ) helped measure the impact of megestrol on malnutrition likelihood in patients experiencing chemotherapy-induced anorexia. The World Health Organization Quality of Life (WHOQOL)-BREF Scale was used to evaluate the quality of life of participants, producing scores related to physical health, psychological well-being, environmental factors, and social relationships. RESULTS: The CiTAs scale assessment indicated that administering megestrol significantly enhanced taste perception among advanced patients with cancer undergoing chemotherapy. Notably, the megestrol group patients showed significantly higher Short Nutritional Assessment Questionnaire (SNAQ) scores than the control group. The megestrol group patients also exhibited higher physiological (PHYS) scores than their control group counterparts. However, this distinction was not statistically significant. The study findings indicate that patients who received megestrol demonstrated significantly higher scores in psychological (PSYCH) and environmental(ENVIR) domains than the control group. Furthermore, megestrol administration was associated with significantly elevated SOCIL and ENVIR levels in patients. CONCLUSION: The proficient efficacy evaluation of megestrol in enhancing appetite, mitigating malnutrition likelihood, and improving the quality of life of chemotherapy-induced anorexic patients can be achieved through taste-related scales.


Asunto(s)
Anorexia , Antineoplásicos , Neoplasias , Calidad de Vida , Humanos , Anorexia/inducido químicamente , Masculino , Femenino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Encuestas y Cuestionarios , Antineoplásicos/efectos adversos , Anciano , Adulto , Acetato de Megestrol/efectos adversos , Acetato de Megestrol/uso terapéutico , Acetato de Megestrol/administración & dosificación , Evaluación Nutricional , Estimulantes del Apetito/uso terapéutico , Estimulantes del Apetito/administración & dosificación , Estimulantes del Apetito/efectos adversos , Gusto/efectos de los fármacos
4.
Front Endocrinol (Lausanne) ; 15: 1308016, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38601207

RESUMEN

In recent years, with the improvement of people's living standards, the incidence of DM has increased year by year in China. DM is a common metabolic syndrome characterized by hyperglycemia caused by genetic, environmental and other factors. At the same time, long-term suffering from DM will also have an impact on the heart, blood vessels, eyes, kidneys and nerves, and associated serious diseases. The human body has a large and complex gut microbiota, which has a significant impact on the body's metabolism. Research shows that the occurrence and development of DM and its complications are closely related to intestinal microbiota. At present, western medicine generally treats DM with drugs. The hypoglycemic effect is fast and strong, but it can have a series of side effects on the human body. Compared with western medicine, Chinese medicine has its unique views and methods in treating DM. TCM can improve symptoms and treat complications by improving the imbalance of microbiota in patients with DM. Its characteristics of health, safety, and reliability are widely accepted by the general public. This article reviews the relationship between intestinal microbiota and DM, as well as the mechanism of TCM intervention in DM by regulating intestinal microbiota.


Asunto(s)
Microbioma Gastrointestinal , Medicina Tradicional China , Humanos , Medicina Tradicional China/métodos , Reproducibilidad de los Resultados , Hipoglucemiantes/farmacología , China
5.
Cancer Lett ; 591: 216871, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38604310

RESUMEN

Chimeric antigen receptor T (CAR-T) cell therapy, as an adoptive immunotherapy, is playing an increasingly important role in the treatment of malignant tumors. CAR-T cells are referred to as "living drugs" as they not only target tumor cells directly, but also induce long-term immune memory that has the potential to provide long-lasting protection. CD19.CAR-T cells have achieved complete response rates of over 90 % for acute lymphoblastic leukemia and over 60 % for non-Hodgkin's lymphoma. However, the response rate of CAR-T cells in the treatment of solid tumors remains extremely low and the side effects potentially severe. In this review, we discuss the limitations that the solid tumor microenvironment poses for CAR-T application and the solutions that are being developed to address these limitations, in the hope that in the near future, CAR-T cell therapy for solid tumors can attain the same success rates as are now being seen clinically for hematological malignancies.

6.
Front Med (Lausanne) ; 11: 1322102, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38606153

RESUMEN

Background: Evidence indicates that chronic non-alcoholic fatty liver disease (NAFLD) can increase the risk of atherosclerosis (AS), but the underlying mechanism remains unclear. Objective: This study is intended for confirming key genes shared between NAFLD and AS, and their clinical diagnostic value to establish a foundation for searching novel therapeutic targets. Methods: We downloaded the Gene Expression Omnibus (GEO) datasets, GSE48452 and GSE89632 for NAFLD and GSE100927, GSE40231 and GSE28829 for AS. The progression of NAFLD co-expression gene modules were recognized via weighted gene co-expression network analysis (WGCNA). We screened for differentially expressed genes (DEGs) associated with AS and identified common genes associated with NAFLD and AS using Venn diagrams. We investigated the most significant core genes between NAFLD and AS using machine learning algorithms. We then constructed a diagnostic model by creating a nomogram and evaluating its performance using ROC curves. Furthermore, the CIBERSORT algorithm was utilized to explore the immune cell infiltration between the two diseases, and evaluate the relationship between diagnostic genes and immune cells. Results: The WGCNA findings associated 1,129 key genes with NAFLD, and the difference analysis results identified 625 DEGs in AS, and 47 genes that were common to both diseases. We screened the core RPS6KA1 and SERPINA3 genes associated with NAFLD and AS using three machine learning algorithms. A nomogram and ROC curves demonstrated that these genes had great clinical meaning. We found differential expression of RPS6KA1 in patients with steatosis and NASH, and of SERPINA3 only in those with NASH compared with normal individuals. Immune infiltration findings revealed that macrophage and mast cell infiltration play important roles in the development of NAFLD and AS. Notably, SERPINA3 correlated negatively, whereas RPS6KA1 correlated positively with macrophages and mast cells. Conclusion: We identified RPS6KA1 and SERPINA3 as potential diagnostic markers for NAFLD and AS. The most promising marker for a diagnosis of NAFLD and AS might be RPS6KA1, whereas SERPINA3 is the most closely related gene for NASH and AS. We believe that further exploration of these core genes will reveal the etiology and a pathological relationship between NAFLD and AS.

7.
ACS Nano ; 18(16): 10818-10828, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38597459

RESUMEN

Rapid advancements in immersive communications and artificial intelligence have created a pressing demand for high-performance tactile sensing gloves capable of delivering high sensitivity and a wide sensing range. Unfortunately, existing tactile sensing gloves fall short in terms of user comfort and are ill-suited for underwater applications. To address these limitations, we propose a flexible hand gesture recognition glove (GRG) that contains high-performance micropillar tactile sensors (MPTSs) inspired by the flexible tube foot of a starfish. The as-prepared flexible sensors offer a wide working range (5 Pa to 450 kPa), superfast response time (23 ms), reliable repeatability (∼10000 cycles), and a low limit of detection. Furthermore, these MPTSs are waterproof, which makes them well-suited for underwater applications. By integrating the high-performance MPTSs with a machine learning algorithm, the proposed GRG system achieves intelligent recognition of 16 hand gestures under water, which significantly extends real-time and effective communication capabilities for divers. The GRG system holds tremendous potential for a wide range of applications in the field of underwater communications.

8.
ArXiv ; 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38659640

RESUMEN

Noninvasive transcranial photoacoustic computed tomography (PACT) of the human brain, despite its clinical potential, remains impeded by the acoustic distortion induced by the human skull. The distortion, which is attributed to the markedly different material properties of the skull relative to soft tissue, results in heavily aberrated PACT images -- a problem that has remained unsolved in the past two decades. Herein, we report the first successful experimental demonstration of the de-aberration of PACT images through an ex-vivo adult human skull using a homogeneous elastic model for the skull. Using only the geometry, position, and orientation of the skull, we accurately de-aberrate the PACT images of light-absorbing phantoms acquired through an ex-vivo human skull, in terms of the recovered phantom features, for different levels of phantom complexity and positions. Our work addresses the longstanding challenge of skull-induced aberrations in transcranial PACT and advances the field towards unlocking the full potential of transcranial human brain PACT.

10.
Sci Adv ; 10(10): eadk1495, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38457506

RESUMEN

Quantum imaging holds potential benefits over classical imaging but has faced challenges such as poor signal-to-noise ratios, low resolvable pixel counts, difficulty in imaging biological organisms, and inability to quantify full birefringence properties. Here, we introduce quantum imaging by coincidence from entanglement (ICE), using spatially and polarization-entangled photon pairs to overcome these challenges. With spatial entanglement, ICE offers higher signal-to-noise ratios, greater resolvable pixel counts, and the ability to image biological organisms. With polarization entanglement, ICE provides quantitative quantum birefringence imaging capability, where both the phase retardation and the principal refractive index axis angle of an object can be remotely and instantly quantified without changing the polarization states of the photons incident on the object. Furthermore, ICE enables 25 times greater suppression of stray light than classical imaging. ICE has the potential to pave the way for quantum imaging in diverse fields, such as life sciences and remote sensing.

11.
Environ Geochem Health ; 46(3): 107, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38446285

RESUMEN

Potentially toxic elements (Pb and Cd) contamination of soil can adversely affect human health. Moreover, these metal ions interact with the gut microbiota after entering the human digestive system. Based on the physiologically based extraction test and the simulator of human intestinal microbial ecosystem, the bioaccessibility of Pb and Cd in soils contaminated with lead-acid power plants was assessed. The gastric stage exhibited the greatest average bioaccessibility of lead and cadmium (63.39% and 57.22%), followed by the small intestinal stage (6.86% and 36.29%); due to gut microorganisms, the bioaccessibility of lead and cadmium was further reduced in the colon stage (1.86% and 4.22%). Furthermore, to investigate soil contamination's effects on gut microbes, 16S rRNA high-throughput sequencing was used to identify the gut microbial species after the colon period. Due to Pb and Cd exposure, the relative abundance of Firmicutes and unidentified_Bacteria decreased, while the relative abundance of Proteobacteria, Synergistota, and Bacteroidota increased. The relationship between environmental factors and the number of microbial species in the gut was also examined using Spearman correlation analysis. Pb and Cd exposure has been found to affect the composition and structure of the gut microbiota.


Asunto(s)
Cadmio , Ecosistema , Humanos , Plomo , ARN Ribosómico 16S/genética , Centrales Eléctricas , Suelo
12.
Med Image Anal ; 94: 103135, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38461654

RESUMEN

Late-life depression (LLD) is a highly prevalent mood disorder occurring in older adults and is frequently accompanied by cognitive impairment (CI). Studies have shown that LLD may increase the risk of Alzheimer's disease (AD). However, the heterogeneity of presentation of geriatric depression suggests that multiple biological mechanisms may underlie it. Current biological research on LLD progression incorporates machine learning that combines neuroimaging data with clinical observations. There are few studies on incident cognitive diagnostic outcomes in LLD based on structural MRI (sMRI). In this paper, we describe the development of a hybrid representation learning (HRL) framework for predicting cognitive diagnosis over 5 years based on T1-weighted sMRI data. Specifically, we first extract prediction-oriented MRI features via a deep neural network, and then integrate them with handcrafted MRI features via a Transformer encoder for cognitive diagnosis prediction. Two tasks are investigated in this work, including (1) identifying cognitively normal subjects with LLD and never-depressed older healthy subjects, and (2) identifying LLD subjects who developed CI (or even AD) and those who stayed cognitively normal over five years. We validate the proposed HRL on 294 subjects with T1-weighted MRIs from two clinically harmonized studies. Experimental results suggest that the HRL outperforms several classical machine learning and state-of-the-art deep learning methods in LLD identification and prediction tasks.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Anciano , Depresión/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Enfermedad de Alzheimer/diagnóstico por imagen , Cognición
13.
Mater Today Bio ; 25: 100978, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38434571

RESUMEN

A life-threatening illness that poses a serious threat to human health is myocardial infarction. It may result in a significant number of myocardial cells dying, dilated left ventricles, dysfunctional heart function, and ultimately cardiac failure. Based on the development of emerging biomaterials and the lack of clinical treatment methods and cardiac donors for myocardial infarction, hydrogels with good compatibility have been gradually applied to the treatment of myocardial infarction. Specifically, based on the three processes of pathophysiology of myocardial infarction, we summarized various types of hydrogels designed for myocardial tissue engineering in recent years, including natural hydrogels, intelligent hydrogels, growth factors, stem cells, and microRNA-loaded hydrogels. In addition, we also describe the heart patch and preparation techniques that promote the repair of MI heart function. Although most of these hydrogels are still in the preclinical research stage and lack of clinical trials, they have great potential for further application in the future. It is expected that this review will improve our knowledge of and offer fresh approaches to treating myocardial infarction.

14.
Nutr J ; 23(1): 33, 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38459491

RESUMEN

BACKGROUND: The relationship between vitamin D status and mortality among adults with hypertension remains unclear. METHODS: This prospective cohort study involved a sample of 19,500 adults with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. We utilized a weighted COX proportional hazard model to assess the association between vitamin D status and mortality. This statistical model calculates hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI). RESULTS: The study indicated that lower serum 25(OH)D concentration was associated with an increased risk of all-cause mortality among individuals with hypertension. Specially. Those with concentrations between 25.0 and 49.9 nmol/L (HR = 1.71, 95%CI = 1.22-2.40) and less than 25.0 nmol/L (HR = 1.97, 95%CI = 1.15-3.39) had higher hazard ratios for all-cause mortality. Individuals with hypertension who took vitamin D supplements had a lower risk of all-cause mortality, but not the risk of CVD mortality (HR 0.75, 95%CI 0.54-1.03), compared to those who did not supplement (HR = 0.76, 95%CI = 0.61-0.94). Subgroup analysis further revealed that vitamin D supplementation was associated with a reduced risk of all-cause mortality among individuals without diabetes (HR = 0.65, 95%CI = 0.52-0.81) and individuals without CVD (HR = 0.75, 95%CI = 0.58-0.97), and a decreased risk of CVD mortality among individuals without diabetes (HR = 0.63, 95%CI = 0.45-0.88) and without CVD (HR = 0.61, 95%CI = 0.40-0.92). Furthermore, higher-dose vitamin D supplementation was also associated with a greater reduction in all-cause mortality among hypertensive individuals, and there was the potential synergistic effect of combining normal-dose calcium and vitamin D supplementation, showing a superior effect on mortality compared to low-dose supplementation in adults with hypertension. CONCLUSIONS: This prospective cohort study demonstrated a significant association between lower serum 25 (OH)D concentration and increased all-cause mortality among adults with hypertension. Furthermore, the study found that vitamin D supplementation had a strong and significantly positive correlation with reduced all-cause and CVD mortality among hypertensive individuals without diabetes or CVD. This positive correlation suggests that vitamin D supplementation could potentially be an effective strategy to reduce the risk of mortality in this specific group of people.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus , Hipertensión , Deficiencia de Vitamina D , Vitamina D/análogos & derivados , Adulto , Humanos , Encuestas Nutricionales , Estudios Prospectivos , Vitaminas , Suplementos Dietéticos
15.
Phys Chem Chem Phys ; 26(12): 9475-9487, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38450519

RESUMEN

Based on the synergistic modulation of electromagnetic parameters and microstructure design, multidimensional porous magnetic carbon-based nanocomposites have become ideal materials with efficient absorption properties. What's more, a carbon-magnetic alloy composite is a commonly used and efficient microwave absorber. In this paper, Co7Fe3/Co@CBC (CFCC) nanocomposites with strong magnetism, a three-phase composition, and a three-dimensional porous structure were synthesized by reducing Fe2+ and Co2+ using chestnut-shell biomass carbon (CBC). Biomass carbon with a higher specific surface area provides numerous active sites for Co7Fe3 nanosheets and Co nanospheres to form three-dimensional ping-pong chrysanthemum-like nanocomposites, which generate rich heterogeneous interfaces and conductive network structures. By adjusting the amount of added biomass, the electromagnetic parameters can be effectively regulated to achieve efficient microwave absorption properties. When the amount of biomass added varies within the range of 1.0 to 2.5 g, all samples exhibit a favorable effective absorption bandwidth (EAB) of over 5.88 GHz. In particular, the CFCC-2.0 composite exhibits optimal microwave absorption properties, with a minimum reflection loss (RLmin) value of -59.25 dB and an EAB of 6.34 GHz at a thickness of 2.8 mm. The simulation and modeling analysis results of radar cross section (RCS) further confirm the exceptional attenuation capability of composite materials at multiple incident angles. The exceptional microwave absorption properties and stability of EAB for the Co7Fe3/Co@CBC nanocomposite make it a promising candidate in the field of absorbing materials. This work also provides some feasible ideas for designing stable broadband wave-absorbing materials.

16.
Oncogene ; 43(13): 931-943, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38341472

RESUMEN

Copy number alterations are crucial for the development of gastric cancer (GC). Here, we identified Transmembrane Protein 65 (TMEM65) amplification by genomic hybridization microarray to profile copy-number variations in GC. TMEM65 mRNA level was significantly up-regulated in GC compared to adjacent normal tissues, and was positively associated with TMEM65 amplification. High TMEM65 expression or DNA copy number predicts poor prognosis (P < 0.05) in GC. Furtherly, GC patients with TMEM65 amplification (n = 129) or overexpression (n = 78) significantly associated with shortened survival. Ectopic expression of TMEM65 significantly promoted cell proliferation, cell cycle progression and cell migration/invasion ability, but inhibited apoptosis (all P < 0.05). Conversely, silencing of TMEM65 in GC cells showed opposite abilities on cell function in vitro and suppressed tumor growth and lung metastasis in vivo (all P < 0.01). Moreover, TMEM65 depletion by VNP-encapsulated TMEM65-siRNA significantly suppressed tumor growth in subcutaneous xenograft model. Mechanistically, TMEM65 exerted oncogenic effects through activating PI3K-Akt-mTOR signaling pathway, as evidenced of increased expression of key regulators (p-Akt, p-GSK-3ß, p-mTOR) by Western blot. YWHAZ (Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase) was identified as a direct downstream effector of TMEM65. Direct binding of TMEM65 with YWHAZ in the cytoplasm inhibited ubiquitin-mediated degradation of YWHAZ. Moreover, oncogenic effect of TMEM65 was partly dependent on YWHAZ. In conclusion, TMEM65 promotes gastric tumorigenesis by activating PI3K-Akt-mTOR signaling via cooperating with YWHAZ. TMEM65 overexpression may serve as an independent new biomarker and is a therapeutic target in GC.


Asunto(s)
Proteínas Proto-Oncogénicas c-akt , Neoplasias Gástricas , Humanos , Proteínas 14-3-3/metabolismo , Carcinogénesis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Transformación Celular Neoplásica , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Factores de Transcripción/metabolismo
17.
Eur J Pharmacol ; 967: 176380, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38311279

RESUMEN

Severe acute pancreatitis-associated acute lung injury (SAP-ALI) remains a significant challenge for healthcare practitioners because of its high morbidity and mortality; therefore, there is an urgent need for an effective treatment. Mesenchymal stem cells (MSCs) have shown significant potential in the treatment of a variety of refractory diseases, including lung diseases. This study aimed to investigate the protective effects of MSCs against SAP-ALI and its underlying mechanisms. Our results suggest that MSCs mitigate pathological injury, hemorrhage, edema, inflammatory response in lung tissue, and lipopolysaccharide (LPS)-induced cell damage in RLE-6TN cells (a rat alveolar epithelial cell line). The results also showed that MSCs, similar to the effects of ferrostatin-1 (ferroptosis inhibitor), suppressed the ferroptosis response, which was manifested as down-regulated Fe2+, malondialdehyde, and reactive oxygen species (ROS) levels, and up-regulated glutathione peroxidase 4 (GPX4) and glutathione (GSH) levels in vivo and in vitro. The activation of ferroptosis by erastin (a ferroptosis agonist) reversed the protective effect of MSCs against SAP-ALI. Furthermore, MSCs activated the nuclear factor erythroid 2 associated factor 2 (Nrf2) transcription factor, and blocking the Nrf2 signaling pathway with ML385 abolished the inhibitory effect of MSCs on ferroptosis in vitro. Collectively, these results suggest that MSCs have therapeutic effects against SAP-ALI. The specific mechanism involves inhibition of ferroptosis by activating the Nrf2 transcription factor.


Asunto(s)
Lesión Pulmonar Aguda , Ferroptosis , Células Madre Mesenquimatosas , Pancreatitis , Animales , Ratas , Enfermedad Aguda , Lesión Pulmonar Aguda/etiología , Antioxidantes/farmacología , Glutatión , Factor 2 Relacionado con NF-E2 , Pancreatitis/complicaciones
18.
PLoS One ; 19(2): e0298974, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38394238

RESUMEN

Relationship Extraction (RE) is a central task in information extraction. The use of entity mapping to address complex scenarios with overlapping triples, such as CasRel, is gaining traction, yet faces challenges such as inadequate consideration of sentence continuity, sample imbalance and data noise. This research introduces an entity mapping-based method CasRelBLCF building on CasRel. The main contributions include: A joint decoder for the head entity, utilizing Bi-LSTM and CRF, integration of the Focal Loss function to tackle sample imbalance and a reinforcement learning-based noise reduction method for handling dataset noise. Experiments on relation extraction datasets indicate the superiority of the CasRelBLCF model and the enhancement on model's performance of the noise reduction method.


Asunto(s)
Almacenamiento y Recuperación de la Información , Refuerzo en Psicología , Lenguaje
19.
Pharm Dev Technol ; 29(3): 143-152, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38353125

RESUMEN

OBJECTIVE: In order to improve the dissolution property of quercetin (QCT), the quercetin nanocrystals (QNCs) were prepared in this study. METHODS: QNCs were prepared by a 100 µm diameter Y-shape microfluidic channel. Some impact factors affecting the generation of QNCs such as concentration and flow rate were investigated. Furthermore, the fluid mixing in the microfluidic channel was simulated by fluid software. RESULTS: XRPD and DSC analyses indicated that the prepared QNCs were amorphous. Stable QNCs with a particle size of 77.9 ± 3.63 nm and polydispersity index of 0.26 ± 0.02 were obtained. TEM showed that the as-prepared QNCs had a uniform spherical shape with an average particle size of about 100-300 nm. In the dissolution medium without cosolvent Tween -80, the dissolution of QCT was poor, its final accumulated dissolution was only 3.95%, while that of QNCs was 66%. CONCLUSION: When QCT was changed to QNCs by microfluidic technology, its dissolution property could be obviously improved. Therefore, microfluidic technology as a new method to prepare nanocrystals has a good applying prospect in improving dissolution property for poorly water-soluble drugs.


Asunto(s)
Nanopartículas , Quercetina , Quercetina/química , Microfluídica , Polisorbatos , Agua , Nanopartículas/química , Tamaño de la Partícula , Solubilidad
20.
Leuk Res ; 138: 107455, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38368721

RESUMEN

OBJECTIVE: To explore the involvement of TFEB-mediated autophagy-lysosomal mechanisms in multiple myeloma (MM) during bortezomib treatment. METHODS: MM cells were exposed to bortezomib or subjected to TFEB knockdown. CCK assay was used to assess the cell proliferation. Western blotting and fluorescent staining were conducted to examine autophagy and lysosomes. The TFEB expression pattern was analyzed, and whole transcriptome sequencing was carried out. Additionally, TFEB target genes were predicted using the GTRD(http://gtrd.biouml.org/) website, and pathway analysis was performed. RESULTS: Bortezomib demonstrated a dose-dependent and time dependent inhibition of cell proliferation. In MM cells treated with bortezomib, LC3B, Beclin-1, TFEB, and Lamp1 exhibited upregulation in a time- and concentration-dependent manner. LysoTracker dye labeling showed an increase in lysosomes in the bortezomib-treated group. Moreover, bortezomib elevated the expression of lysosome-associated factor Lamp1. Bortezomib promoted the nuclear translocation of TFEB, leading to decreased cytoplasmic TFEB and increased nuclear TFEB. TFEB gene silencing reversed bortezomib's inhibitory effect on MM cell lines, significantly reducing autophagosome expression and lysosome numbers. Furthermore, bioinformatic analysis identified the MAPK pathway as a potential downstream target of TFEB. CONCLUSION: Bortezomib effectively inhibits MM cell proliferation and induces autophagy, partly through TFEB-mediated mechanisms, with potential involvement of the MAPK pathway.


Asunto(s)
Mieloma Múltiple , Humanos , Bortezomib/farmacología , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/genética , Mieloma Múltiple/metabolismo , Autofagia , Autofagosomas/metabolismo , Lisosomas/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética
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