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1.
Nat Med ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38839897

RESUMEN

Gene therapy is a promising approach for hereditary deafness. We recently showed that unilateral AAV1-hOTOF gene therapy with dual adeno-associated virus (AAV) serotype 1 carrying human OTOF transgene is safe and associated with functional improvements in patients with autosomal recessive deafness 9 (DFNB9). The protocol was subsequently amended and approved to allow bilateral gene therapy administration. Here we report an interim analysis of the single-arm trial investigating the safety and efficacy of binaural therapy in five pediatric patients with DFNB9. The primary endpoint was dose-limiting toxicity at 6 weeks, and the secondary endpoint included safety (adverse events) and efficacy (auditory function and speech perception). No dose-limiting toxicity or serious adverse event occurred. A total of 36 adverse events occurred. The most common adverse events were increased lymphocyte counts (6 out of 36) and increased cholesterol levels (6 out of 36). All patients had bilateral hearing restoration. The average auditory brainstem response threshold in the right (left) ear was >95 dB (>95 dB) in all patients at baseline, and the average auditory brainstem response threshold in the right (left) ear was restored to 58 dB (58 dB) in patient 1, 75 dB (85 dB) in patient 2, 55 dB (50 dB) in patient 3 at 26 weeks, and 75 dB (78 dB) in patient 4 and 63 dB (63 dB) in patient 5 at 13 weeks. The speech perception and the capability of sound source localization were restored in all five patients. These results provide preliminary insights on the safety and efficacy of binaural AAV gene therapy for hereditary deafness. The trial is ongoing with longer follow-up to confirm the safety and efficacy findings. Chinese Clinical Trial Registry registration: ChiCTR2200063181 .

2.
Eur J Pharmacol ; : 176711, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38839029

RESUMEN

Histone deacetylase (HDAC) inhibitors are potential candidates for treating pulmonary fibrosis. MPT0E028, a novel pan-HDAC inhibitor, has been reported to exhibit antitumor activity in several cancer cell lines. In this study, we investigated the mechanism underlying the inhibitory effects of MPT0E028 on the expression of fibrogenic proteins in human lung fibroblasts (WI-38). Our results revealed that MPT0E028 inhibited transforming growth factor-ß (TGF-ß)-, thrombin-, and endothelin 1-induced connective tissue growth factor (CTGF) expression in a concentration-dependent manner. In addition, MPT0E028 suppressed TGF-ß-stimulated expression of fibronectin, collagen I, and α-smooth muscle actin (α-SMA). Furthermore, MPT0E028 inhibited the TGF-ß-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK). MPT0E028 reduced the increase in SMAD3 and c-Jun phosphorylation, and SMAD3- and activator protein-1 (AP-1)-luciferase activities under TGF-ß stimulation. Transfection with mitogen-activated protein kinase phosphatase-1 (MKP-1) siRNA reversed the suppressive effects of MPT0E028 on TGF-ß-induced increases in CTGF expression; JNK, p38, and ERK phosphorylation; and SMAD3 and AP-1 activation. Moreover, MPT0E028 increased MKP-1 acetylation and activity in WI-38 cells. Pretreatment with MPT0E028 reduced the fibrosis score and fibronectin, collagen, and α-SMA expression in bleomycin-induced pulmonary fibrosis mice. In conclusion, MPT0E028 induced MKP-1 acetylation and activation, which in turn inhibited TGF-ß-stimulated JNK, p38, and ERK phosphorylation; SMAD3 and AP-1 activation; and subsequent CTGF expression in human lung fibroblasts. Thus, MPT0E028 may be a potential drug for treating pulmonary fibrosis.

3.
Am J Otolaryngol ; 45(4): 104342, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38703609

RESUMEN

OBJECTIVE: To develop a multi-instance learning (MIL) based artificial intelligence (AI)-assisted diagnosis models by using laryngoscopic images to differentiate benign and malignant vocal fold leukoplakia (VFL). METHODS: The AI system was developed, trained and validated on 5362 images of 551 patients from three hospitals. Automated regions of interest (ROI) segmentation algorithm was utilized to construct image-level features. MIL was used to fusion image level results to patient level features, then the extracted features were modeled by seven machine learning algorithms. Finally, we evaluated the image level and patient level results. Additionally, 50 videos of VFL were prospectively gathered to assess the system's real-time diagnostic capabilities. A human-machine comparison database was also constructed to compare the diagnostic performance of otolaryngologists with and without AI assistance. RESULTS: In internal and external validation sets, the maximum area under the curve (AUC) for image level segmentation models was 0.775 (95 % CI 0.740-0.811) and 0.720 (95 % CI 0.684-0.756), respectively. Utilizing a MIL-based fusion strategy, the AUC at the patient level increased to 0.869 (95 % CI 0.798-0.940) and 0.851 (95 % CI 0.756-0.945). For real-time video diagnosis, the maximum AUC at the patient level reached 0.850 (95 % CI, 0.743-0.957). With AI assistance, the AUC improved from 0.720 (95 % CI 0.682-0.755) to 0.808 (95 % CI 0.775-0.839) for senior otolaryngologists and from 0.647 (95 % CI 0.608-0.686) to 0.807 (95 % CI 0.773-0.837) for junior otolaryngologists. CONCLUSIONS: The MIL based AI-assisted diagnosis system can significantly improve the diagnostic performance of otolaryngologists for VFL and help to make proper clinical decisions.

5.
Dev Cell ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38776924

RESUMEN

A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells. We find that SMARCA5 is required to maintain aberrant chromatin accessibility for leukemogenesis and then promotes transcriptional activation of AKR1B1, an aldo/keto reductase, by recruiting transcription co-activator DDX5 and transcription factor SP1. Higher levels of AKR1B1 are associated with a poor prognosis in leukemia patients and promote leukemogenesis by reprogramming fructose metabolism. Moreover, pharmacological inhibition of AKR1B1 has been shown to have significant therapeutic effects in leukemia mice and leukemia patient cells. Thus, our findings link the aberrant chromatin state mediated by SMARCA5 to AKR1B1-mediated endogenous fructose metabolism reprogramming and shed light on the essential role of AKR1B1 in leukemogenesis, which may provide therapeutic strategies for leukemia.

6.
Diabetes Metab Syndr Obes ; 17: 2013-2019, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38765470

RESUMEN

Objective: To analyze the correlation between body mass index (BMI) and clinicopathological factors of papillary thyroid cancer (PTC). Methods: The clinical data of patients with PCT who were hospitalized in the Department of Thyroid Surgery of the Affiliated Hospital of Guizhou Medical University from March 2023 to September 2023 were retrospectively collected, including age, gender, height, weight, BMI, v-raf murine sarcoma viral oncogene homolog B (BRAF) gene mutation, tumor size, multifocus, Hashimoto's thyroiditis, lymph node metastasis and other clinicopathological factors. According to the World Health Organization (WHO) definition for Asian population, BMI≥25kg/m2 was obese group, 23≤BMI≤24.9kg/m2 was overweight group, 18.5≤BMI≤22.9kg/m2 was normal weight group, and BMI≤18.5kg/m2 was low weight group. The clinicopathological factors of overweight and obese patients with PTC were analyzed. Results: A total of 164 PTC patients were included, with an average BMI of (24.44±3.57) kg/m2. Age of overweight and obese PTC patients (Z=1.978, p=0.083); Gender of overweight and obese PTC patients (χ2 value: 11.570, p=0.004); Tumor size in overweight and obese PTC patients (Z=0.894, p=0.411); BRAF gene mutation in overweight and obese PTC patients (χ2 value: 1.452, p =0.623); Multifocal lesions were found in overweight and obese patients (χ2 value: 1.653, p =0.201). Hashimoto's thyroiditis was found in overweight and obese PTC patients (χ2 value: 1.147, p=0.298). Overweight and obese patients with PTC had lymph node metastasis (χ2 value: 1.690, p =0.251). Conclusion: Overweight and obesity in PTC patients are correlated with male, but not with age, tumor size, BRAF mutation, multifocality, Hashimoto's thyroiditis and lymph node metastasis.

7.
Laryngoscope ; 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38801129

RESUMEN

OBJECTIVES: Vocal fold leukoplakia (VFL) is a precancerous lesion of laryngeal cancer, and its endoscopic diagnosis poses challenges. We aim to develop an artificial intelligence (AI) model using white light imaging (WLI) and narrow-band imaging (NBI) to distinguish benign from malignant VFL. METHODS: A total of 7057 images from 426 patients were used for model development and internal validation. Additionally, 1617 images from two other hospitals were used for model external validation. Modeling learning based on WLI and NBI modalities was conducted using deep learning combined with a multi-instance learning approach (MIL). Furthermore, 50 prospectively collected videos were used to evaluate real-time model performance. A human-machine comparison involving 100 patients and 12 laryngologists assessed the real-world effectiveness of the model. RESULTS: The model achieved the highest area under the receiver operating characteristic curve (AUC) values of 0.868 and 0.884 in the internal and external validation sets, respectively. AUC in the video validation set was 0.825 (95% CI: 0.704-0.946). In the human-machine comparison, AI significantly improved AUC and accuracy for all laryngologists (p < 0.05). With the assistance of AI, the diagnostic abilities and consistency of all laryngologists improved. CONCLUSIONS: Our multicenter study developed an effective AI model using MIL and fusion of WLI and NBI images for VFL diagnosis, particularly aiding junior laryngologists. However, further optimization and validation are necessary to fully assess its potential impact in clinical settings. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

8.
Crit Pathw Cardiol ; 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38598544

RESUMEN

It is well known that individuals with liver cirrhosis are considered high risk for cardiac surgery, with an increased risk for morbidity and mortality as the liver disease progresses. In the last decade, there have been considerable advances in transcatheter aortic valve implantation (TAVI) as an alternative to surgical aortic valve replacement (SAVR) in individuals deemed to high risk for surgery. However, research surrounding TAVI in the setting of liver cirrhosis has not been as widely studied. In this national population-based cohort study, we evaluated the trends of mortality, complications, and healthcare utilization in liver cirrhotic patients undergoing TAVI, as well as analyze the basic demographics of these individuals. We found that from 2011-2020, the amount of TAVI procedures conducted in cirrhotic patients was increasing annually while the mortality, procedural complications, and healthcare utilization trends in these cirrhotic patients undergoing TAVI decreased. Overall, TAVI does seem to be a reasonable management for aortic stenosis patients with liver cirrhosis who need aortic valve replacement.

9.
Front Oncol ; 14: 1355643, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38651157

RESUMEN

Background: The low rates of durable response against relapsed/refractory multiple myeloma (RRMM) in recent studies prompt that chimeric antigen receptor (CAR)-T cell therapies are yet to be optimized. The combined anti-BCMA and anti-CD19 CAR-T cell therapy showed high clinical efficacy in several clinical trials for RRMM. We here conducted a meta-analysis to confirm its efficacy and safety. Methods: We collected data from Embase, Web of Science, PubMed, CNKI, Wanfang and Cochrane databases up to April 2023. We extracted and evaluated data related to the efficacy and safety of combined anti-BCMA and anti-CD19 CAR-T cell therapies in RRMM patients. The data was then analyzed using RevMan5.4 and StataSE-64 software. PROSPERO number was CRD42023455002. Results: Our meta-analysis included 12 relevant clinical trials involving 347 RRMM patients who were treated with combined anti-BCMA and anti-CD19 CAR-T cell therapies. For efficacy assessment, the pooled overall response rate (ORR) was 94% (95% CI: 91%-98%), the complete response rate (CRR) was 50% (95% CI: 29%-71%), and the minimal residual disease (MRD) negativity rate within responders was 73% (95% CI: 66%-80%). In terms of safety, the pooled all-grade cytokine release syndrome (CRS) rate was 98% (95% CI: 97%-100%), grade≥3 CRS rate was 9% (95% CI: 4%-14%), and the incidence of neurotoxicity was 8% (95% CI: 4%-11%). Of hematologic toxicity, neutropenia was 82% (95% CI: 75%-89%), anemia was 71% (95% CI: 53%-90%), thrombocytopenia was 67% (95% CI: 40%-93%) and infection was 42% (95% CI: 9%-76%). The median progression-free survival (PFS) was 12.97 months (95% CI: 6.02-19.91), and the median overall survival (OS) was 26.63 months (95% CI: 8.14-45.11). Conclusions: As a novel immunotherapy strategy with great potential, the combined anti-BCMA and anti-CD19 CAR-T cell therapy showed high efficacy in RRMM, but its safety needs further improvement. This meta-analysis suggests possible optimization of combined CAR-T therapy. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023455002.

10.
Curr Res Food Sci ; 8: 100727, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38577418

RESUMEN

The favorable inhibitory effect of tea polyphenols on heterocyclic aromatic amines (HAAs) has been confirmed in many past studies. The objective of this study was to investigate the structure-activity relationship of catechins that act as inhibitors of HAA formation in chemical models. Two kinds of quantitative structure-activity relationship models for catechin-inhibiting-HAA were established. We chose two kinds of HAAs including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and five catechins including epigallocatechin gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC), epicatechin (EC), and catechin (C). The inhibitory effect of five catechins were in the following order: EGCG > ECG > EGC > C > EC. Thereinto, EGCG and ECG showed dramatically better inhibition on the formation of PhIP and MeIQx, especially EGCG. Further, the mechanisms of catechin-inhibiting-HAA were speculated by correlation analysis. The free radical-scavenging ability was predicted to be the most relevant to the inhibitory effect of ECG, EGC, EC and C on HAAs. Differently, the phenylacetaldehyde-trapping ability might be the more important mechanism of EGCG inhibiting PhIP in chemical model system. This study may bring a broader idea for controlling the formation of HAAs according to the structure of catechins.

12.
Dev Comp Immunol ; 156: 105176, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38582249

RESUMEN

Due to the ongoing global warming, the risk of heatwaves in the oceans is continuously increasing while our understanding of the physiological response of Litopenaeus vannamei under extreme temperature conditions remains limited. Therefore, this study aimed to evaluate the physiological responses of L. vannamei under heat stress. Our results indicated that as temperature rose, the structure of intestinal and hepatopancreatic tissues was damaged sequentially. Activity of immune-related enzymes (acid phosphatase/alkaline phosphatase) initially increased before decreased, while antioxidant enzymes (superoxide dismutase and glutathione-S transferase) activity and malondialdehyde content increased with rising temperature. In addition, the total antioxidant capacity decreased with rising temperature. With the rising temperature, there was a significant increase in the expression of caspase-3, heat shock protein 70, lipopolysaccharide-induced tumor necrosis factor-α, transcriptional enhanced associate domain and yorkie in intestinal and hepatopancreatic tissues. Following heat stress, the number of potentially beneficial bacteria (Rhodobacteraceae and Gemmonbacter) increased which maintain balance and promote vitamin synthesis. Intestinal transcriptome analysis revealed 852 differentially expressed genes in the heat stress group compared with the control group. KEGG functional annotation results showed that the endocrine system was the most abundant in Organismal systems followed by the immune system. These results indicated that heat stress leads to tissue damage in shrimp, however the shrimp may respond to stress through a coordinated interaction strategy of the endocrine system, immune system and gut microbiota. This study revealed the response mechanism of L. vannamei to acute heat stress and potentially provided a theoretical foundation for future research on shrimp environmental adaptations.


Asunto(s)
Microbioma Gastrointestinal , Respuesta al Choque Térmico , Penaeidae , Transcriptoma , Animales , Penaeidae/inmunología , Penaeidae/microbiología , Penaeidae/genética , Respuesta al Choque Térmico/genética , Respuesta al Choque Térmico/inmunología , Microbioma Gastrointestinal/inmunología , Intestinos/inmunología , Intestinos/microbiología , Sistema Inmunológico/metabolismo , Sistema Inmunológico/inmunología , Perfilación de la Expresión Génica , Hepatopáncreas/inmunología , Hepatopáncreas/metabolismo , Proteínas de Artrópodos/metabolismo , Proteínas de Artrópodos/genética , Antioxidantes/metabolismo
13.
Aging (Albany NY) ; 16(8): 7188-7216, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38643462

RESUMEN

BACKGROUND: This study aims to identify the essential cell cycle-related genes associated with prognosis in breast cancer (BRCA), and to verify the relationship between the central gene and immune infiltration, so as to provide detailed and comprehensive information for the treatment of BRCA. MATERIALS AND METHODS: Gene expression profiles (GSE10780, GSE21422, GSE61304) and the Cancer Genome Atlas (TCGA) BRCA data were used to identify differentially expressed genes (DEGs) and further functional enrichment analysis. STRING and Cytoscape were employed for the protein-protein interaction (PPI) network construction. TPX2 was viewed as the crucial prognostic gene by the Survival and Cox analysis. Furthermore, the connection between TPX2 expression and immune infiltrating cells and immune checkpoints in BRCA was also performed by the TIMER online database and R software. RESULTS: A total of 18 cell cycle-related DEGs were identified in this study. Subsequently, an intersection analysis based on TCGA-BRCA prognostic genes and the above DEGs identified three genes (TPX2, UBE2C, CCNE2) as crucial prognostic candidate biomarkers. Moreover, we also demonstrated that TPX2 is closely associated with immune infiltration in BRCA and a positive relation between TPX2 and PD-L1 expression was firstly detected. CONCLUSIONS: These results revealed that TPX2 is a potential prognostic biomarker and closely correlated with immune infiltration in BRCA, which could provide powerful and efficient strategies for breast cancer immunotherapy.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , Proteínas de Ciclo Celular , Regulación Neoplásica de la Expresión Génica , Proteínas Asociadas a Microtúbulos , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/mortalidad , Femenino , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Biomarcadores de Tumor/genética , Pronóstico , Proteínas Asociadas a Microtúbulos/genética , Mapas de Interacción de Proteínas/genética , Perfilación de la Expresión Génica , Ciclo Celular/genética , Bases de Datos Genéticas
14.
Sci Total Environ ; 923: 171451, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38438027

RESUMEN

This research presents the successful development and optimization of a spiropyran-assisted cellulose aerogel (CNF-SP) aerogel with UV-induced switchable wettability, and the evaluation of its performance as an effective oil sorbent for oil spill cleanup. The aerogel initially exhibited strong hydrophobicity (124°) and showed UV-induced switchable wettability due to the photo-response structure of spiropyran. Upon UV irradiation, the hydrophobicity of the aerogel could be switched to hydrophilicity (31°), while visible light irradiation could restore its hydrophobicity. The three-dimensional (3D) porous structure of the CNF-SP aerogel combined with the hydrophobic properties of spiropyranol led to its great oil adsorption performance (27-30 g/g of oil adsorption ratio). The central composite design (CCD) was applied to optimize the aerogel and investigate the effects of raw material ratio (i.e., carboxymethyl cellulose, carboxyethyl spiropyran, polyvinyl alcohol, and nano zinc oxide) on the oil sorption performance of the aerogel. The optimized CNF-SP aerogel demonstrated a high oil sorption efficiency, particularly in acid and cold environments. Moreover, the switchable function indicated that the aerogel exhibited reusability and renewability, with the added benefit of UV-induced oil recovery.

15.
Foods ; 13(6)2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38540809

RESUMEN

The nonantimicrobial properties and relatively poor mechanical properties of hydroxyethyl cellulose (HEC) limit its use in packaging. Sulfated rice bran polysaccharides (SRBP) possess significant antioxidant and antimicrobial activities. The purpose of this study was to investigate the effect of different concentrations of SRBP on the physical and mechanical properties and the functional characteristics of HEC/SRBP films. The physical properties of the HEC/20% SRBP films, such as water resistance, water vapor barrier, light barrier, and tensile strength, improved significantly (p < 0.05) compared with those of the HEC films. Scanning electron microscopy and Fourier transform infrared spectrometry showed that HEC formed hydrogen bonds with SRBP and exhibited better compatibility. Thermogravimetric analysis revealed that the addition of SRBP was beneficial to the thermal stability of the films. In addition, the antioxidant and bacteriostatic properties of the films were enhanced by the addition of SRBP to HEC, with the 20% SRBP films showing the most significant enhancement in activity. Therefore, the HEC/20% SRBP films show potential for development for use as active food packaging.

16.
Front Med (Lausanne) ; 11: 1349070, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38533316

RESUMEN

The C-reactive protein-to-albumin ratio (CAR) and neutrophil-to-albumin ratio (NAR) serve as established markers for inflammatory diseases. However, limited studies have investigated their potential in predicting response and prognosis following infliximab (IFX) treatment. The objective of this paper was to evaluate feasibility of CAR and NAR as biomarkers to assess response to IFX induction therapy. Additionally, we attempted to determine the capacity to predict clinical remission in ulcerative colitis (UC) after 54 weeks of IFX treatment. We enrolled a total of 157 UC patients diagnosed via endoscopic mucosal biopsy at our hospital between October 2018 and June 2023. Additionally, 199 patients presenting with gastrointestinal symptoms, who underwent physical examinations, constituted the control group. Comprehensive clinical data, laboratory indicators, and endoscopic findings were systematically collected. CAR and NAR values were computed before treatment, post-induction, and subsequently at 8-week intervals. Comparisons between two groups were analyzed using the Wilcoxon rank-sum test or the independent samples t-test, and comparisons between multiple groups were analyzed using the one-way ANOVA (analysis of variance) or the Kruskal-Wallis rank sum test. We found CAR and NAR emerged as sensitive biomarkers for assessing disease activity. Notably, our findings indicated their dual predictive capability: foreseeing response post-IFX induction therapy and prognosticating the likelihood of UC patients achieving clinical remission following 54 weeks on IFX therapy.

17.
Adv Mater ; : e2309770, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38447017

RESUMEN

Percutaneous thermotherapy, a minimally invasive operational procedure, is employed in the ablation of deep tumor lesions by means of target-delivering heat. Conventional thermal ablation methods, such as radiofrequency or microwave ablation, to a certain extent, are subjected to extended ablation time as well as biosafety risks of unwanted overheating. Given its effectiveness and safety, percutaneous thermotherapy gains a fresh perspective, thanks to magnetic hyperthermia. In this respect, an injectable- and magnetic-hydrogel-construct-based thermal ablation agent is likely to be a candidate for the aforementioned clinical translation. Adopting a simple and environment-friendly strategy, a magnetic colloidal hydrogel injection is introduced by a binary system comprising super-paramagnetic Fe3O4 nanoparticles and gelatin nanoparticles. The colloidal hydrogel constructs, unlike conventional bulk hydrogel, can be easily extruded through a percutaneous needle and then self-heal in a reversible manner owing to the unique electrostatic cross-linking. The introduction of magnetic building blocks is exhibited with a rapid magnetothermal response to an alternating magnetic field. Such hydrogel injection is capable of generating heat without limitation of deep penetration. The materials achieve outstanding therapeutic results in mouse and rabbit models. These findings constitute a new class of locoregional interventional thermal therapies with minimal collateral damages.

18.
Biochem Pharmacol ; 223: 116138, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38494062

RESUMEN

Central nervous system lymphoma (CNSL) is a type of hematological tumor. Treatment of CNSL is difficult due to the existence of the blood-brain barrier (BBB). Here, we used exosomes (Exos), a type of extracellular vesicle, and iRGD to construct a new drug carrier system and use it to load doxorubicin (DOX). The results of in vitro and in vivo experiments showed that the iRGD-Exo-DOX system can efficiently and securely transport DOX through the BBB and target tumor cells. The results suggest that iRGD-Exo-DOX may cross the BBB through brain microvascular endothelial cell-mediated endocytosis. Together, our study indicates an impactful treatment of central nervous system tumors.


Asunto(s)
Neoplasias del Sistema Nervioso Central , Linfoma , Humanos , Barrera Hematoencefálica , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Portadores de Fármacos , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Línea Celular Tumoral
19.
J Hazard Mater ; 469: 133832, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38428295

RESUMEN

Effective marine oil spill responses are vital to reduce environmental, societal, and economic damage. This study developed a Multi-Criteria Emergency Response System (MC-ERS) to comprehensively evaluate response efficiency, operational costs, and environmental losses. The proposed system integrates dynamic multiphase simulation of oil weathering and oil cleanup processes and further provides effective planning for multi-stage resource allocation through system optimization. The developed weight-sum model improved the performance of response operations by reducing the complexity of multi-criteria decision-making. Particle Swarm Optimization (PSO) was chosen as the foundational optimization algorithm due to its efficiency in rapid convergence and suitability for complex problems. From extensive comparisons of PSO variants across benchmark functions and inertia strategies, the C-PSO algorithm was developed, demonstrating enhanced optimization performance for MC-ERS. The developed modelling system performance was demonstrated and evaluated through a representative case study. The optimization plan coordinated resource allocation from onshore warehouses to harbors and spill sites, balancing oil recovery efficiency, costs, and ecological losses. Optimized results indicate an oil recovery of up to 76.50% in five days. Additionally, the system cuts costs by 3.45% and environmental losses by 15.75%. The findings enhance the efficiency of marine oil spill emergency response and provide support for such incidents.

20.
Food Chem ; 446: 138849, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38460280

RESUMEN

Polycyclic aromatic hydrocarbons (PAHs), prominent carcinogens formed during food processing, pose health risks through long-term consumption. This study focuses on 16 priority PAHs in the European Union, investigating their formation during pyrolysis. Glucose, amino acids and fatty acids are important food nutrients. To further explore whether these nutrients in food form PAHs during heating, a single chemical model method was used to heat these nutrients respectively, and GC-MS/MS was used to identify and quantify the obtained components. Glucose is the most basic nutrient in food, so the influence of water, pH, temperature and other factors on the formation of PAHs was studied in the glucose model. At the same time, the models of amino acids and fatty acids were used to assist in improving the entire nutrient research system. According to our results, some previously reported mechanisms of PAHs formation by fatty acids heating were confirmed. In addition, glucose and amino acids could also produce many PAHs after heating, and some conclusions were improved by comparing the intermediates of PAHs from three types of nutrients.


Asunto(s)
Aminoácidos , Hidrocarburos Policíclicos Aromáticos , Ácidos Grasos , Glucosa , Modelos Químicos , Espectrometría de Masas en Tándem , Nutrientes
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