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1.
Value Health ; 2024 Jul 06.
Article de Anglais | MEDLINE | ID: mdl-38977183

RÉSUMÉ

OBJECTIVES: Health technology assessment (HTA) is increasingly crucial in medicine price negotiations in China, yet prior appraisals revealed national discrepancies on key economic evaluation issues: willingness-to-pay (WTP) threshold, pricing models for multi-indication medicines, and comparator selection principles. This study aims to collect expert opinions on these issues for future HTA evaluations. METHODS: A nationwide anonymous web-based survey encompassing experts across academia, HTA, consultancy/contract research organization (CRO)/industry, service provider and payer. In 2023, a generic invitation containing a web link to the questionnaire was disseminated via WeChat using convenience and snowball sampling. Agreement rates for questionnaire views were analyzed using descriptive statistics. The relationship between participants' responses and demographics was examined using appropriate logistic models. RESULTS: 303 responses were received from experts in 34 cities. Key expert views include: a suggested base WTP threshold ranging from 0.5 to 1.5 times GDP (52.1% agreement); elevated thresholds for childhood diseases, rare diseases, end-of-life diseases, and first-in-class medicines (FICs) (>78.0% agreement); a single pricing model for multi-indication medicines (60.4% agreement); consideration of multiple medicines as comparators (79.9% agreement); and avoiding the use of centrally procured medicines as comparators for medicines with a time-to-market under three years (71.0% agreement). Participants who are service provider had lower odds of selecting higher thresholds (OR: 0.26; P<0.01) compared with responders from consultancy/CRO/industry. CONCLUSIONS: Expert views indicate the need for substantial changes in China's current HTA methods, highlighting the need for increased investment in HTA processes and expertise cultivation.

2.
Article de Anglais | MEDLINE | ID: mdl-39001735

RÉSUMÉ

Coronary artery disease continues to be the leading cause of death globally. Identifying patients who are at risk of coronary artery disease remains a public health priority. At present, the focus of cardiovascular disease prevention relies heavily on probabilistic risk scoring despite no randomized controlled trials demonstrating their efficacy. The concept of using imaging to guide preventative therapy is not new, but has previously focused on indirect measures such as carotid intima-media thickening or coronary artery calcification. In recent trials, patients found to have coronary artery disease on computed tomography (CT) coronary angiography were more likely to be started on preventative therapy and had lower rates of cardiac events. This led to the design of the SCOT-HEART 2 (Scottish Computed Tomography of the Heart 2) trial, which aims to determine whether screening with the use of CT coronary angiography is more clinically effective than cardiovascular risk scoring to guide the use of primary preventative therapies and reduce the risk of myocardial infarction.

3.
Commun Biol ; 7(1): 807, 2024 Jul 03.
Article de Anglais | MEDLINE | ID: mdl-38961177

RÉSUMÉ

Glaucoma is the leading cause of irreversible blindness and is characterized by progressive retinal ganglion cell (RGC) loss and retinal nerve fiber layer thinning. Currently, no existing treatment is effective for the preservation of RGCs. MicroRNA-22-3p (miR22) and small extracellular vesicles derived from mesenchymal stem cells (MSC-sEVs) have neuroprotective effects. In this study, we apply miR22-overexpressing MSC-sEVs in an N-methyl-D-aspartic acid (NMDA)-induced RGC injury model to assess their short-term therapeutic effects and explore the underlying mechanisms. We find that mice in the miR22-sEVs-treated group have thicker retinas, fewer apoptotic cells, more reserved RGCs, better retinal function, and lower expression levels of Bax and caspase-3. MiR22-sEVs treatment promotes viability, inhibits apoptosis and inhibits Bax and caspase-3 expression in RGC-5 cells. MiR22 targets mitogen-activated protein kinase kinase kinase 12 to inhibit apoptosis by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Collectively, our results suggest that miR22-sEVs ameliorate NMDA-induced RGC injury through the inhibition of MAPK signaling pathway-mediated apoptosis, providing a potential therapy for glaucoma and other diseases that involve RGC damage.


Sujet(s)
Vésicules extracellulaires , Système de signalisation des MAP kinases , Cellules souches mésenchymateuses , microARN , Cellules ganglionnaires rétiniennes , Cellules ganglionnaires rétiniennes/métabolisme , microARN/génétique , microARN/métabolisme , Animaux , Cellules souches mésenchymateuses/métabolisme , Vésicules extracellulaires/métabolisme , Souris , Apoptose , Souris de lignée C57BL , Glaucome/génétique , Glaucome/métabolisme , Glaucome/anatomopathologie , Glaucome/thérapie , Mâle
4.
Sheng Wu Gong Cheng Xue Bao ; 40(7): 2346-2356, 2024 Jul 25.
Article de Chinois | MEDLINE | ID: mdl-39044596

RÉSUMÉ

To achieve rapid detection of enramycin in feed, we employed the competitive inhibition method to develop a colloidal gold immunochromatographic test strip based on the anti-enramycin A monoclonal antibody (anti-Er.A-mAb). Colloidal gold probes were prepared with a laboratory-prepared high-purity anti-Er.A-mAb. The effects of pH, antibody titer, and antigen concentration (test line) on the test strip performance were investigated. The colloidal gold test strip prepared with 8 µL potassium carbonate addition, 4 µg/mL antibody, 1.0 mg/mL antigen (test line), and 3 µL gold-labeled antibody showed acceptable specificity and a low limit of detection. The test strip showed the detection limit of 25 ng/mL for enramycin A, with a linear range of 25-300 ng/mL. The experiments on the feed with positive sample addition proved that the test strip had good repeatability and was more sensitive than high-performance liquid chromatography, being applicable for the rapid detection of enramycin in large batches of feed samples.


Sujet(s)
Aliment pour animaux , Anticorps monoclonaux , Chromatographie d'affinité , Or colloïdal , Or colloïdal/composition chimique , Anticorps monoclonaux/immunologie , Anticorps monoclonaux/composition chimique , Chromatographie d'affinité/méthodes , Aliment pour animaux/analyse , Nébramycine/analyse , Nébramycine/analogues et dérivés , Contamination des aliments/analyse , Résidus de médicaments/analyse
5.
Chemistry ; : e202401935, 2024 Jul 23.
Article de Anglais | MEDLINE | ID: mdl-39042471

RÉSUMÉ

Low temperature has been a major challenge for lithium-ion batteries (LIBs) to maintain satisfied electrochemical performance, and the main reason is the deactivation of electrolyte with the decreasing temperature. To address this point, in present work, we develop a low-temperature resistant electrolyte which includes ethyl acetate (EA) and fluoroethylene carbonate (FEC) as solvent and lithium difluoro(oxalato)borate (LiDFOB) as the primary lithium salt. Due to the preferential decomposition of LiDFOB and FEC, a solid electrolyte interface rich in LiF is formed on the lithium metal anodes (LMAs) and lithium cobalt oxide (LCO) cathodes, contributing to higher stability and rapid desolvation of Li+ ions. The batteries with the optimized electrolyte can undergo cycling tests at -40 °C, with a capacity retention of 83.9 % after 200 cycles. Furthermore, the optimized electrolyte exhibits excellent compatibility with both LCO cathodes and graphite (Gr) anodes, enabling a Gr/LCO battery to maintain a capacity retention of 90.3 % after multiple cycles at -25 °C. This work proposes a cost-effective electrolyte that can activate potential LIBs in practical scenarios, especially in low-temperature environments.

6.
Biol Trace Elem Res ; 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38954322

RÉSUMÉ

This study investigated heavy metal contamination in dried fish sold in Guangzhou, China, and evaluated the resultant non-carcinogenic and carcinogenic health risks. Dried fish samples were purchased from Baiyun, Tianhe, Panyu, and Yuexiu districts in Guangzhou, where the population is substantial. They were randomly acquired in bustling supermarkets and farmers' markets, targeting the most popular dried fish in these areas. Sixty samples from five dried fish types (Stolephorus chinensis, Thamnaconus modestus, Nemipterus-virgatus, river fish, Ctenopharyngodon idella) were analyzed for chromium (Cr), arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg) content. Quantification of the heavy metals were carried out by inductively coupled plasma mass spectrometry (ICP-MS) for Cr, As, Cd, and Pb, and an automatic mercury analyzer for Hg. The median concentration of these heavy metals in dried fish were 0.358 mg/kg, 2.653 mg/kg, 0.032 mg/kg, 0.083 mg/kg, and 0.042 mg/kg, respectively. Pollution severity was ranked as dried Nemipterus-virgatus > dried Stolephorus chinensis > dried Thamnaconus modestus > dried river fish > dried Ctenopharyngodon idella, with As being the most predominant pollutant. All fish types showed severe As pollution. Non-carcinogenic risks were identified in the consumption of dried Nemipterus-virgatus and dried Stolephorus chinensis for both genders, while potential carcinogenic risks were associated with four of the fish types. Women faced higher health risks than men from dried fish consumption. Consequently, we advise consumers to minimize their intake of dried fish and regulatory agencies conduct regular monitoring of heavy metal levels in commercially available dried fish to avert potential health risks.

7.
ACS Sens ; 2024 Jul 06.
Article de Anglais | MEDLINE | ID: mdl-38970501

RÉSUMÉ

The combination of closed bipolar electrodes (cBPE) with electrochemiluminescence (ECL) imaging has demonstrated remarkable capabilities in the field of bioanalysis. Here, we established a cBPE-ECL platform for ultrasensitive detection of alkaline phosphatase (ALP) and two-dimensional imaging of epidermal growth factor receptor (EGFR). This cBPE-ECL system consists of a high-density gold nanowire array in anodic aluminum oxide (AAO) membrane as the cBPE coupled with ECL of highly luminescent cadmium selenide quantum dots (CdSe QDs) luminophores to achieve cathodic electro-optical conversion. When an enzyme-catalyzed amplification effect of ALP with 4-aminophenyl phosphate monosodium salt hydrate (p-APP) as the substrate and 4-aminophenol (p-AP) as the electroactive probe is introduced, a significant improvement of sensing sensitivity with a detection limit as low as 0.5 fM for ALP on the cBPE-ECL platform can be obtained. In addition, the cBPE-ECL sensing system can also be used to detect cancer cells with an impressive detection limit of 50 cells/mL by labeling ALP onto the EGFR protein on A431 human epidermal cancer cell membranes. Thus, two-dimensional (2D) imaging of the EGFR proteins on the cell surface can be achieved, demonstrating that the established cBPE-ECL sensing system is of high resolution for spatiotemporal cell imaging.

8.
Genes Genomics ; 2024 Jul 11.
Article de Anglais | MEDLINE | ID: mdl-38990270

RÉSUMÉ

BACKGROUND: In humans, ACTN2 mutations are identified as highly relevant to a range of cardiomyopathies such as DCM and HCM, while their association with sudden cardiac death has been observed in forensic cases. Although ACTN2 has been shown to regulate sarcomere Z-disc organization, a causal relationship between ACTN2 dysregulation and cardiomyopathies under chronic stress has not yet been investigated. OBJECTIVE: In this work, we explored the relationship between Actn2 dysregulation and cardiomyopathies under dexamethasone treatment. METHODS: Previous cases of ACTN2 mutations were collected and the conservative analysis was carried out by MEGA 11, the possible impact on the stability and function of ACTN2 affected by these mutations was predicted by Polyphen-2. ACTN2 was suppressed by siRNA in H9c2 cells under dexamethasone treatment to mimic the chronic stress in vitro. Then the cardiac hypertrophic molecular biomarkers were elevated, and the potential pathways were explored by transcriptome analysis. RESULTS: Actn2 suppression impaired calcium uptake and increased hypertrophy in H9c2 cells under dexamethasone treatment. Concomitantly, hypertrophic molecular biomarkers were also elevated in Actn2-suppressed cells. Further transcriptome analysis and Western blotting data suggested that Actn2 suppression led to the excessive activation of the MAPK pathway and ERK cascade. In vitro pharmaceutical intervention with ERK inhibitors could partially reverse the morphological changes and inhibit the excessive cardiac hypertrophic molecular biomarkers in H9c2 cells. CONCLUSION: Our study revealed a functional role of ACTN2 under chronic stress, loss of ACTN2 function accelerated H9c2 hypertrophy through ERK signaling. A commercial drug, Ibudilast, was identified to reverse cell hypertrophy in vitro.

9.
Sci Total Environ ; 947: 174512, 2024 Jul 05.
Article de Anglais | MEDLINE | ID: mdl-38972406

RÉSUMÉ

Neonicotinoid pesticides (NNPs) and microplastics (MPs) are two emerging contaminants in agricultural environment. However, the interaction between MPs (especially biodegradable plastics) and NNPs is currently unclear. Therefore, taking thiacloprid (THI) as an example of NNPs, this study explores the adsorption-desorption process and mechanism of NNPs on MPs (traditional and biodegradable plastics), and analyzed the main factors affecting the adsorption (pH, salinity and dissolved organic matter). In addition, by using diffusive gradients in thin-films device, this study assessed the impact of MPs on the bioavailability of NNPs in soil. The results showed that the maximum adsorption capacity of polyamide 6 (96.49 µg g-1) for THI was greater than that of poly (butylene adipate co-terephthalate) (88.78 µg g-1). Aging increased the adsorption amount of THI (5.53 %-15.8 %) due to the higher specific surface area and reduced contact angle of MPs, but the adsorption mechanism remained unchanged. The desorption amount of THI from MPs in simulated intestinal fluid is 1.30-1.36 times. The MPs in soil alter the distribution of THI in the soil, increasing the bioavailability of THI while inhibiting its degradation. The results highlighted the significance of examining the combined pollution caused by MPs and NNPs.

10.
ACS Nano ; 18(29): 19200-19207, 2024 Jul 23.
Article de Anglais | MEDLINE | ID: mdl-38996344

RÉSUMÉ

Simultaneous detection and structural characterization of protein variants on a single platform are highly desirable but technically challenging. Herein, we present a single-molecule spectral system based on a gold plasmonic nanopore for analyzing two peptides and their single-point mutated variants. The gold plasmonic nanopore enabled the high-throughput acquisition of surface-enhanced Raman scattering (SERS) spectra at the single-molecule level by electrically driving analytes into hot spots. Furthermore, a statistical method based on Boolean operations was developed to extract prominent features from fluctuated single-molecule SERS spectra. The effects of the single-amino acid substitutions on both the intramolecular interactions and the peptide conformations were directly characterized by the nanopore system, and the results agreed with the predictions by AlphaFold2. This study highlights the mutual benefits of spectroscopy and nanopore technology, whereby the gold plasmonic nanopore offers a powerful tool for the structural analysis of single-molecule proteins.


Sujet(s)
Substitution d'acide aminé , Or , Nanopores , Peptides , Analyse spectrale Raman , Or/composition chimique , Analyse spectrale Raman/méthodes , Peptides/composition chimique , Propriétés de surface
11.
Anal Chem ; 96(24): 9808-9816, 2024 Jun 18.
Article de Anglais | MEDLINE | ID: mdl-38833718

RÉSUMÉ

Visualization of the mitochondrial state is crucial for tracking cell life processes and diagnosing disease, while fluorescent probes that can accurately assess mitochondrial status are currently scarce. Herein, a fluorescent probe named "SYN" was designed and prepared, which can target mitochondria via the mitochondrial membrane potential. Upon pathology or external stimulation, SYN can be released from the mitochondria and accumulate in the nucleolus to monitor the status of mitochondria. During this process, the brightness of the nucleolus can then serve as an indicator of mitochondrial damage. SYN has demonstrated excellent photostability in live cells as well as an extremely inert fluorescence response to bioactive molecules and the physiological pH environment of live cells. Spectroscopic titration and molecular docking studies have revealed that SYN can be lit up in nucleoli due to the high viscosity of the nucleus and the strong electrostatic interaction with the phosphate backbone of RNA. This probe is expected to be an exceptional tool based on its excellent imaging properties for tracking mitochondrial state in live cells.


Sujet(s)
Nucléole , Colorants fluorescents , Mitochondries , Mitochondries/métabolisme , Mitochondries/composition chimique , Humains , Colorants fluorescents/composition chimique , Nucléole/métabolisme , Cellules HeLa , Simulation de docking moléculaire , Imagerie optique , Potentiel de membrane mitochondriale
12.
Molecules ; 29(12)2024 Jun 19.
Article de Anglais | MEDLINE | ID: mdl-38930980

RÉSUMÉ

Two-dimensional MXenes have become an important material for electrochemical sensing of biomolecules due to their excellent electric properties, large surface area and hydrophilicity. However, the simultaneous detection of multiple biomolecules using MXene-based electrodes is still a challenge. Here, a simple solvothermal process was used to synthesis the Ti3C2Tx coated with TiO2 nanosheets (Ti3C2Tx@TiO2 NSs). The surface modification of TiO2 NSs on Ti3C2Tx can effectively reduce the self-accumulation of Ti3C2Tx and improve stability. Glassy carbon electrode was modified by Ti3C2Tx@TiO2 NSs (Ti3C2Tx@TiO2 NSs/GCE) and was able simultaneously to detect dopamine (DA), ascorbic acid (AA) and uric acid (UA). Under concentrations ranging from 200 to 1000 µM, 40 to 300 µM and 50 to 400 µM, the limit of detection (LOD) is 2.91 µM, 0.19 µM and 0.25 µM for AA, DA and UA, respectively. Furthermore, Ti3C2Tx@TiO2 NSs/GCE demonstrated remarkable stability and reliable reproducibility for the detection of AA/DA/UA.


Sujet(s)
Acide ascorbique , Dopamine , Nanostructures , Titane , Acide urique , Titane/composition chimique , Acide urique/analyse , Acide urique/composition chimique , Dopamine/analyse , Acide ascorbique/analyse , Acide ascorbique/composition chimique , Nanostructures/composition chimique , Limite de détection , Techniques électrochimiques/méthodes , Électrodes , Reproductibilité des résultats , Techniques de biocapteur/méthodes
13.
Sci Data ; 11(1): 687, 2024 Jun 25.
Article de Anglais | MEDLINE | ID: mdl-38918497

RÉSUMÉ

Cardiac magnetic resonance imaging (CMR) has emerged as a valuable diagnostic tool for cardiac diseases. However, a significant drawback of CMR is its slow imaging speed, resulting in low patient throughput and compromised clinical diagnostic quality. The limited temporal resolution also causes patient discomfort and introduces artifacts in the images, further diminishing their overall quality and diagnostic value. There has been growing interest in deep learning-based CMR imaging algorithms that can reconstruct high-quality images from highly under-sampled k-space data. However, the development of deep learning methods requires large training datasets, which have so far not been made publicly available for CMR. To address this gap, we released a dataset that includes multi-contrast, multi-view, multi-slice and multi-coil CMR imaging data from 300 subjects. Imaging studies include cardiac cine and mapping sequences. The 'CMRxRecon' dataset contains raw k-space data and auto-calibration lines. Our aim is to facilitate the advancement of state-of-the-art CMR image reconstruction by introducing standardized evaluation criteria and making the dataset freely accessible to the research community.


Sujet(s)
Apprentissage profond , Imagerie par résonance magnétique , Humains , Algorithmes , Coeur/imagerie diagnostique , Cardiopathies/imagerie diagnostique , Traitement d'image par ordinateur/méthodes
14.
Mater Horiz ; 11(14): 3287-3297, 2024 Jul 15.
Article de Anglais | MEDLINE | ID: mdl-38842407

RÉSUMÉ

Eukaryotic cells regulate various cellular processes through membrane-bound and membrane-less organelles, enabling active signal communication and material exchange. Lysosomes and lipid droplets are representative organelles, contributing to cell lipophagy when their interaction and metabolism are disrupted. Our limited understanding of the interacting behaviours and physicochemical properties of different organelles during lipophagy hinders accurate diagnosis and treatment of related diseases. In this contribution, we report a fluorescent probe, PTZ, engineered for dual-targeting of lipid droplets and lysosomes. PTZ can track liquid-liquid phase separation and respond to polarity shifts through ratiometric fluorescence emission, elucidating the lipophagy process from the perspective of organelle behavior and physicochemical properties. Leveraging on the multifunctionality of PTZ, we have successfully tracked the polarity and dynamic changes of lysosomes and lipid droplets during lipophagy. Furthermore, an unknown homogeneous transition of lipid droplets and lysosomes was discovered, which provided a new perspective for understanding lipophagy processes. And this work is expected to serve as a reference for diagnosis and treatment of lipophagy-related diseases.


Sujet(s)
Colorants fluorescents , Gouttelettes lipidiques , Lysosomes , Humains , Lysosomes/métabolisme , Gouttelettes lipidiques/métabolisme , Transition de phase , Autophagie/physiologie , Cellules HeLa
15.
Environ Sci Technol ; 2024 Jun 11.
Article de Anglais | MEDLINE | ID: mdl-38860911

RÉSUMÉ

Foliar assimilation of elemental mercury (Hg0) from the atmosphere plays a critical role in the global Hg biogeochemical cycle, leading to atmospheric Hg removal and soil Hg insertion. Recent studies have estimated global foliar Hg assimilation; however, large uncertainties remained due to coarse accounting of observed foliar Hg concentrations, posing a substantial challenge in constraining the global Hg budget. Here, we integrated a comprehensive observation database of foliar Hg concentrations and machine learning algorithms to predict the first spatial distribution of foliar Hg concentrations on a global scale, contributing to the first estimate of global Hg pools in foliage. The global average of foliar Hg concentrations was estimated to be 24.0 ng g-1 (7.5-56.5 ng g-1), and the global total in foliar Hg pools reached 4561.3 Mg (1455.2-9062.8 Mg). The spatial distribution showed the hotspots in tropical regions, including the Amazon, Central Africa, and Southeast Asia. A range of 2268.5-2727.0 Mg yr-1 was estimated for annual foliar Hg assimilation accounting for the perennial continuous assimilation by evergreen vegetation foliage. The first spatial maps of foliar Hg concentrations and Hg pools may aid in understanding the global biogeochemical cycling of Hg, especially in the context of climate change and global vegetation greening.

16.
Chem Sci ; 15(22): 8422-8429, 2024 Jun 05.
Article de Anglais | MEDLINE | ID: mdl-38846403

RÉSUMÉ

Designing artificial photocatalysts for CO2 reduction is challenging, mainly due to the intrinsic difficulty of making multiple functional units cooperate efficiently. Herein, three-dimensional metal covalent organic frameworks (3D MCOFs) were employed as an innovative platform to integrate a strong Ru(ii) light-harvesting unit, an active Re(i) catalytic center, and an efficient charge separation configuration for photocatalysis. The photosensitive moiety was precisely stabilized into the covalent skeleton by using a rational-designed Ru(ii) complex as one of the building units, while the Re(i) center was linked via a shared bridging ligand with an Ru(ii) center, opening an effective pathway for their electronic interaction. Remarkably, the as-synthesized MCOF exhibited impressive CO2 photoreduction activity with a CO generation rate as high as 1840 µmol g-1 h-1 and 97.7% selectivity. The femtosecond transient absorption spectroscopy combined with theoretical calculations uncovered the fast charge-transfer dynamics occurring between the photoactive and catalytic centers, providing a comprehensive understanding of the photocatalytic mechanism. This work offers in-depth insight into the design of MCOF-based photocatalysts for solar energy utilization.

17.
J Opt Soc Am A Opt Image Sci Vis ; 41(6): 1082-1088, 2024 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-38856420

RÉSUMÉ

The high sensitivity of photoplethysmography (PPG) spectral signals provides conditions for extracting dynamic spectra carrying nonlinear information. By the idea of spatial conversion precision, this paper uses a spectral camera to collect highly sensitive spectral data of 24 wavelengths and proposes a method for extracting dynamic spectra of three different optical path lengths and their joint modeling. In the experiment, the models of the red blood cells and white blood cells established by the joint spectra achieved good results, with the correlation coefficients above 0.77. This study has great significance for achieving high-precision noninvasive quantitative analysis of human blood components.


Sujet(s)
Dynamique non linéaire , Photopléthysmographie , Photopléthysmographie/instrumentation , Humains , Analyse spectrale , Traitement du signal assisté par ordinateur , Érythrocytes/cytologie
18.
J Cancer ; 15(12): 3766-3780, 2024.
Article de Anglais | MEDLINE | ID: mdl-38911372

RÉSUMÉ

Background: The role of endothelial cells in tumor progression is considerable, yet the effect of endothelial cell immune-related genes (EIRGs) is still unclear. This research aimed to scrutinize the prognostic value of EIRGs in lung adenocarcinoma (LUAD) and provide further insights into the abovementioned uncertainties. Methods: After single-cell RNA sequencing (scRNA-seq) samples were obtained from the Gene Expression Omnibus (GEO) database, they were integrated with bulk RNA sequencing data from The Cancer Genome Atlas (TCGA). Prognostic markers were determined and a prognostic model was developed. From this model, a nomogram was constructed. We analyzed the biological mechanism of the EIRGs in LUAD, including functional enrichment, tumor mutational burden (TMB), tumor microenvironment (TME) analyses and drug sensitivity. We validated the signature by validating the external cohort GSE31210 and RT-qPCR. Results: After analyzing the model constructed from eight EIRGs, we observed that high-risk group (HG) LUAD patients (a risk score exceeding 4.65) exhibited unfavorable outcomes according to Kaplan‒Meier survival curves. This outcome was confirmed by GSE31210. The nomogram based on the model demonstrated significant predictive value. HG was influenced primarily by steroid hormone biosynthesis and ECM receptor interactions. The TMB in HGs was greater than that in the LG. Analysis of drug sensitivity revealed the direction for individualized treatment for both risk cohorts. Variations in the expression of EIRGs have been confirmed via RT-qPCR in several LUAD cell lines. Conclusions: The prognostic model and nomogram above are valuable for determining the survival rate and treatment options for LUAD patients.

19.
Int J Nanomedicine ; 19: 6015-6033, 2024.
Article de Anglais | MEDLINE | ID: mdl-38911504

RÉSUMÉ

Wound healing in diabetic patients is frequently hampered. Adipose-derived stem cell exosomes (ADSC-eoxs), serving as a crucial mode of intercellular communication, exhibit promising therapeutic roles in facilitating wound healing. This review aims to comprehensively outline the molecular mechanisms through which ADSC-eoxs enhance diabetic wound healing. We emphasize the biologically active molecules released by these exosomes and their involvement in signaling pathways associated with inflammation modulation, cellular proliferation, vascular neogenesis, and other pertinent processes. Additionally, the clinical application prospects of the reported ADSC-eoxs are also deliberated. A thorough understanding of these molecular mechanisms and potential applications is anticipated to furnish a theoretical groundwork for combating diabetic wound healing.


Sujet(s)
Tissu adipeux , Exosomes , Cellules souches , Cicatrisation de plaie , Humains , Cicatrisation de plaie/physiologie , Tissu adipeux/cytologie , Animaux , Diabète/thérapie , Transduction du signal , Prolifération cellulaire/effets des médicaments et des substances chimiques
20.
Front Oncol ; 14: 1396339, 2024.
Article de Anglais | MEDLINE | ID: mdl-38912066

RÉSUMÉ

Background: In recent years, the incidence of adenocarcinoma of the esophagogastric junction (AEG) has been rapidly increasing globally. Despite advances in the diagnosis and treatment of AEG, the overall prognosis for AEG patients remains concerning. Therefore, analyzing prognostic factors for AEG patients of Siewert type II and constructing a prognostic model for AEG patients is important. Methods: Data of primary Siewert type II AEG patients from the SEER database from 2004 to 2015 were obtained and randomly divided into training and internal validation cohort. Additionally, data of primary Siewert type II AEG patients from the China Medical University Dandong Central Hospital from 2012 to 2018 were collected for external validation. Each variable in the training set underwent univariate Cox analysis, and variables with statistical significance (p < 0.05) were added to the LASSO equation for feature selection. Multivariate Cox analysis was then conducted to determine the independent predictive factors. A nomogram for predicting overall survival (OS) was developed, and its performance was evaluated using ROC curves, calibration curves, and decision curves. NRI and IDI were calculated to assess the improvement of the new prediction model relative to TNM staging. Patients were stratified into high-risk and low-risk groups based on the risk scores from the nomogram. Results: Age, Differentiation grade, T stage, M stage, and LODDS (Log Odds of Positive Lymph Nodes)were independent prognostic factors for OS. The AUC values of the ROC curves for the nomogram in the training set, internal validation set, and external validation set were all greater than 0.7 and higher than those of TNM staging alone. Calibration curves indicated consistency between the predicted and actual outcomes. Decision curve analysis showed moderate net benefit. The NRI and IDI values of the nomogram were greater than 0 in the training, internal validation, and external validation sets. Risk stratification based on the nomogram's risk score demonstrated significant differences in survival rates between the high-risk and low-risk groups. Conclusion: We developed and validated a nomogram for predicting overall survival (OS) in patients with Siewert type II AEG, which assists clinicians in accurately predicting mortality risk and recommending personalized treatment strategies.

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