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1.
Meat Sci ; 216: 109585, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38959640

RESUMEN

In this study, the effect of sodium alginate and quaternized chitosan bis-polysaccharide-based shell transport curcumin nano-emulsions (Cur@QCS/SA) on the microbiological, physicochemical properties, quality characteristics of Harbin red sausage during storage is investigated. According to the microbiological results, the shelf life of Harbin red sausage is extended from 3 d to 6 d by adding 0.15% Cur@QCS/SA, and Bacillus is the most predominant bacterial before 6 d. Additionally, the physicochemical properties change significantly, the pH, weight loss (WL), water holding capacity (WHC), water activity (aw), L*, and a* of red sausage decrease gradually with the extension of storage time, as well as b*, lipid oxidation, proteolysis increase significantly (P < 0.05). Secondly, it is found that 0.15% treatment group can better maintain the quality characteristics of Harbin red sausage according to texture profile analysis (TPA), electronic nose (E-nose), and electronic tongue (E-tongue) (P < 0.05). This study provides a new way for nano-emulsions in food applications and a new option for the preservation of Harbin red sausage as well as other low-temperature meat products.

2.
Medicine (Baltimore) ; 103(27): e38782, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38968524

RESUMEN

Lumbar spinal stenosis (LSS) can cause a range of cauda equina symptoms, including lower back and leg pain, numbness, and intermittent claudication. This disease affects approximately 103 million people worldwide, particularly the elderly, and can seriously compromise their health and well-being. Ligamentum flavum hypertrophy (LFH) is one of the main contributing factors to this disease. Surgical treatment is currently recommended for LSS caused by LFH. For patients who do not meet the criteria for surgery, symptom relief can be achieved by using oral nonsteroidal anti-inflammatory drugs (NSAIDs) and epidural steroid injections. Exercise therapy and needle knife can also help to reduce the effects of mechanical stress. However, the effectiveness of these methods varies, and targeting the delay in LF hypertrophy is challenging. Therefore, further research and development of new drugs is necessary to address this issue. Several new drugs, including cyclopamine and N-acetyl-l-cysteine, are currently undergoing testing and may serve as new treatments for LSS caused by LFH.


Asunto(s)
Hipertrofia , Ligamento Amarillo , Vértebras Lumbares , Estenosis Espinal , Humanos , Ligamento Amarillo/patología , Estenosis Espinal/terapia , Estenosis Espinal/etiología , Hipertrofia/etiología , Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios no Esteroideos/administración & dosificación , Terapia por Ejercicio/métodos , Tratamiento Conservador/métodos
3.
Front Pharmacol ; 15: 1391399, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38974035

RESUMEN

Objective: JianPiHuaTan Formula (JPHTF), a traditional Chinese medicine (TCM), has been utilized as an adjunctive therapy for colorectal cancer (CRC). The study aims to evaluate the potential clinical benefits of JPHTF and its effectiveness in inhibiting tumor growth. Methods: 300 stage II/III CRC patients and 412 advanced CRC patients were enrolled to verify the clinical value of JPHTF in CRC treatment. Furthermore, CRC patient-derived xenograft (PDX) mice were utilized to investigate the regulatory mechanisms of JPHTF. Results: JPHTF significantly improved abdominal distension, shortness of breath, drowsiness, loss of appetite, sleep, and tiredness in stage II/III CRC patients, thereby improving their quality of life. Simultaneously, JPHTF served as a supportive therapy in extending the overall survival (OS) of stage IV CRC patients with RAS/RAF mutations undergoing chemotherapy. Additionally, JPHTF effectively impeded tumor progression in CRC PDX models with RAS mutation, accompanied by a reduction in tumor cell content in the JPHTF group. Transcriptomic analysis revealed the involvement of the Hippo and Hedgehog signaling pathways in JPHTF-mediated CRC inhibition. Furthermore, mice in the JPHTF group exhibited increased immune cell infiltration. Conclusion: These findings suggested that JPHTF may inhibits tumor growth in CRC with RAS mutation by modulating RAS/RAF downstream signaling pathways, specifically the Hippo and Hedgehog signaling, leading to increased immune cell infiltration.

4.
CNS Neurosci Ther ; 30(7): e14827, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38992878

RESUMEN

AIMS: This multicenter prospective cohort study (registration no. ChiCTR2000032089) aimed to investigate the relationship between saliva and plasma levetiracetam concentrations to determine whether saliva could be used for routine monitoring of levetiracetam during pregnancy. METHODS: The slot concentrations of levetiracetam in simultaneously obtained saliva and plasma samples were measured using UPLC-MS/MS. The correlations between saliva and plasma levetiracetam concentrations and the dose-normalized concentrations were compared among pregnant women in different stages and nonpregnant control participants with epilepsy. RESULTS: In total, 231 patients with 407 plasma and saliva sample pairs were enrolled from 39 centers. Linear relationships between salivary and plasma levetiracetam concentrations were reported in the enrolled population (r = 0.898, p < 0.001), including pregnant (r = 0.935, p < 0.001) and nonpregnant participants (r = 0.882, p < 0.001). Plasma concentrations were moderately higher than saliva concentrations, with ratios of saliva to plasma concentrations of 0.98 for nonpregnant women, 0.98, 1, and 1.12 for pregnant women during the first trimester, the second trimester, the and third trimester, respectively. The effective range of saliva levetiracetam concentration was found to be 9.98 µg/mL (lower limit) with an area under the curve (AUC) of 0.937 (95% confidence intervals, 0.915-0.959), sensitivity of 88.9%, specificity of 86.8%, and p < 0.001, to 24.05 µg/mL (upper limit) with an AUC of 0.952 (0.914-0.99), sensitivity of 100%, specificity of 92.3%, and p = 0.007. CONCLUSION: The saliva/plasma concentration ratio of levetiracetam remains constant during pregnancy and is similar to that in non-pregnant individuals. Monitoring levetiracetam concentration in saliva during pregnancy should be widely promoted.


Asunto(s)
Anticonvulsivantes , Epilepsia , Levetiracetam , Saliva , Humanos , Levetiracetam/farmacocinética , Levetiracetam/sangre , Femenino , Saliva/química , Saliva/metabolismo , Embarazo , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/sangre , Anticonvulsivantes/análisis , Adulto , Epilepsia/tratamiento farmacológico , Epilepsia/sangre , Adulto Joven , Monitoreo de Drogas/métodos , Piracetam/análogos & derivados , Piracetam/análisis , Piracetam/farmacocinética , Piracetam/sangre , Estudios Prospectivos , Estudios de Cohortes , Espectrometría de Masas en Tándem/métodos
5.
Artículo en Inglés | MEDLINE | ID: mdl-39001814

RESUMEN

Objective Lipotoxicity is a well-established contributor to cardiomyocyte death and heart damage, with ferroptosis being identified as a crucial death mode in cardiomyocyte disease. This study aims to explore the potential role and mechanism of ferroptosis in lipotoxicity-induced myocardial injury. Methods Eight-weeks high-fat diet (HFD) SD rat and H9c2 cardiomyocytes treated with palmitic acid (PA) were established for in vivo and in vitro lipotoxic model. Ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) were used to inhibit ferroptosis. Myocardial-specific STING knockdown rat (Stingmyo-KD) with HFD was further introduced. Rat cardiac structure and function, cell viability, the level of lipid peroxidation, malondialdehyde (MDA), glutathione (GSH), mitochondrial function, ferroptosis related proteins and STING pathway related proteins in H9c2 cells/myocardium were detected. Results HFD rats with ferroptosis inhibitor showed improved cardiac structure and function, reduced lipid peroxidation and restored GSH, which was further confirmed in H9c2 cell. The time-dependent activation of the STING pathway following PA stimulation was observed. Knockdown the expression of STING could reduce PA-induced cell death, lipid peroxidation and MDA levels while restoring the GSH. In addition, both HFD Stingmyo-KD rats and HFD rats with systematic inhibited by STING inhibitor exhibited mitigating lipotoxicity-induced myocardial ferroptosis and reducing myocardial injury. Innovation and conclusion These findings suggest that lipotoxicity can induce ferroptosis in cardiomyocytes through the activation of the STING pathway, providing new targets, and strategies for the treatment of lipotoxicity cardiomyopathy.

6.
Drug Resist Updat ; 76: 101095, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38986165

RESUMEN

BACKGROUND: Response to immunotherapy is the main challenge of head and neck squamous cancer (HNSCC) treatment. Previous studies have indicated that tumor mutational burden (TMB) is associated with prognosis, but it is not always a precise index. Hence, investigating specific genetic mutations and tumor microenvironment (TME) changes in TMB-high patients is essential for precision therapy of HNSCC. METHODS: A total of 33 HNSCC patients were enrolled in this study. We calculated the TMB score based on next-generation sequencing (NGS) sequencing and grouped these patients based on TMB score. Then, we examined the immune microenvironment of HNSCC using assessments of the bulk transcriptome and the single-cell RNA sequence (scRNA-seq) focusing on the molecular nature of TMB and mutations in HNSCC from our cohort. The association of the mutation pattern and TMB was analyzed in The Cancer Genome Atlas (TCGA) and validated by our cohort. RESULTS: 33 HNSCC patients were divided into three groups (TMB-low, -medium, and -high) based on TMB score. In the result of 520-gene panel sequencing data, we found that FAT1 and LRP1B mutations were highly prevalent in TMB-high patients. FAT1 mutations are associated with resistance to immunotherapy in HNSCC patients. This involves many metabolism-related pathways like RERE, AIRE, HOMER1, etc. In the scRNA-seq data, regulatory T cells (Tregs), monocytes, and DCs were found mainly enriched in TMB-high samples. CONCLUSION: Our analysis unraveled the FAT1 gene as an assistant predictor when we use TMB as a biomarker of drug resistance in HNSCC. Tregs, monocytes, and dendritic cells (DCs) were found mainly enriched in TMB-high samples.

7.
Animal Model Exp Med ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38988280

RESUMEN

BACKGROUND: Dengue fever, an acute insect-borne infectious disease caused by the dengue virus (DENV), poses a great challenge to global public health. Hepatic involvement is the most common complication of severe dengue and is closely related to the occurrence and development of disease. However, the features of adaptive immune responses associated with liver injury in severe dengue are not clear. METHODS: We used single-cell sequencing to examine the liver tissues of mild or severe dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection, and the immune interaction between macrophages and T cells. Flow cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single-cell sequencing results. RESULTS: Our result showed CTLs were significantly activated in the severe liver injury group but the immune function-related signal pathway was down-regulated. The reason may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type, and the macrophages then inhibit T cell immunity through the TGF-ß signaling pathway. In addition, the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury mice. CONCLUSIONS: In this study, single-cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever mice. Our study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.

8.
Shanghai Kou Qiang Yi Xue ; 33(2): 219-224, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-39005103

RESUMEN

PURPOSE: To summarize the ultrasound, CT and MRI manifestations of Warthin-like mucoepidermoid carcinoma (WT-MEC), and to explore its imaging characteristics, so as to provide reference for clinical and preoperative diagnosis. METHODS: The clinical information and imaging data of ultrasound, CT and MRI of 12 patients with WT-MEC diagnosed by pathology in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2017 to December 2021 were collected, and their specific characteristics were retrospectively summarized. RESULTS: Among the 12 WT-MEC patients, there were 7 males and 5 females, with an average age of (42.7±16) years. Seven cases underwent ultrasound examination, 6 cases underwent CT examination, and 2 cases underwent MRI examination. Radiologically, all the lesions presented as a solitary mass. 11/12 lesions(91.7%) were identified as well-defined margins, and 10/12(83.3%) as solid-cystic masses. All solid-cystic lesions contained multiple cystic areas with variable sizes. On US images, most lesions showed mixed-echoic echogenicity(5/7, 71.4%), poor vascularization (6/7, 85.7%) and acoustic enhancement (6/7, 85.7%). CT revealed all the lesions (6/6, 100%) as a soft-tissue mass with heterogeneous enhancement (5/6, 83.3%). MRI imaging demonstrated the neoplasm with low or iso-signal intensity on plain T1WI and hyperintensity on T2WI. The heterogeneous enhancement was shown on contrast-enhanced T1WI. CONCLUSIONS: Most WT-MECs represent as a solitary, well-defined, solid-cystic mass in the parotid gland. The neoplasm may be characterized by the multiple and variable-sized cystic components within the tumor.


Asunto(s)
Carcinoma Mucoepidermoide , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Ultrasonografía , Humanos , Carcinoma Mucoepidermoide/diagnóstico por imagen , Masculino , Femenino , Adulto , Ultrasonografía/métodos , Estudios Retrospectivos , Adenolinfoma/diagnóstico por imagen , Neoplasias de la Parótida/diagnóstico por imagen , Persona de Mediana Edad
9.
Artículo en Inglés | MEDLINE | ID: mdl-39046129

RESUMEN

Platinum(II) drugs as a first-line anticancer reagent are limited by side effects and drug resistance. Stimuli-responsive nanosystems hold promise for precise spatiotemporal manipulation of drug delivery, with the aim to promote bioavailability and minimize side effects. Herein, a multitargeting octahedral platinum(IV) prodrug with octadecyl aliphatic chain and histone deacetylase inhibitor (phenylbutyric acid, PHB) at axial positions to improve the therapeutic effect of cisplatin was loaded on the upconversion nanoparticles (UCNPs) through hydrophobic interaction. Followed attachment of DSPE-PEG2000 and arginine-glycine-aspartic (RGD) peptide endowed the nanovehicles with high biocompatibility and tumor specificity. The fabricated nanoparticles (UCNP/Pt(IV)-RGD) can be triggered by upconversion luminescence (UCL) irradiation and glutathione (GSH) reduction to controllably release Pt(II) species and PHB, inducing profound cytotoxicity. Both in vitro and in vivo experiments demonstrated that UCNP/Pt(IV)-RGD exhibited remarkable antitumor efficiency, high tumor-targeting specificity, and real-time UCL imaging capacity, presenting an intelligent platinum(IV) prodrug-loaded nanovehicle for UCL-guided dual-stimuli-responsive combination therapy.

10.
Acta Biomater ; 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39038749

RESUMEN

Pathogenic bacteria are closely associated with the occurrence, development and metastasis of oral squamous cell carcinoma (OSCC). Antibacterial therapy has been considered an enhancement strategy to suppress bacteria-associated tumors and promote anti-tumor immune responses. Herein, we developed an injectable adhesive hydrogel, PNIPAM/DL@TIR, for the in situ photothermal ablation and robust stimulation of antitumor immunity against OSCC colonized by Porphyromonas gingivalis (Pg), one of the major oral pathogenic bacteria. PNIPAM/DL@TIR, composed of poly(N-isopropylacrylamide), demethylated lignin, and TAT peptide-conjugated IR820, was prepared using a simple dissolve-dry-swell solvent exchange method. Upon 808 nm laser irradiation, PNIPAM/DL@TIR exerted photothermal effects to ablate Pg-colonized OSCC and generate dual tumor and bacterial antigens. Owing to its large number of catechol groups, PNIPAM/DL@TIR efficiently captured these antigens to form an in situ antigen repository, thereby eliciting robust and durable antitumor immune responses. Proteomic analysis revealed that the captured antigens comprised both tumor neoantigens and bacterial antigens. The catechol groups endowed PNIPAM/DL@TIR with antioxidant activity, which was also conducive to stimulating antitumor immunity. Altogether, this study develops an injectable adhesive hydrogel and provides a combination strategy for treating bacteria-associated OSCC. STATEMENT OF SIGNIFICANCE: In this study, we developed an injectable adhesive hydrogel, PNIPAM/DL@TIR, for in situ photothermal ablation and robust stimulation of antitumor immunity against OSCC colonized by Porphyromonas gingivalis, one of the major oral pathogenic bacteria. PNIPAM/DL@TIR, which consists of poly(N-isopropylacrylamide), demethylated lignin, and TAT peptide-conjugated IR820 exhibited outstanding photothermal performance. Owing to the presence of catechol groups, PNIPAM/DL@TIR has good bioadhesive properties and can capture protein antigens to form in situ antigen repository, thus initiating robust and long-term antitumor immune responses. In addition, PNIPAM/DL@TIR exhibited strong antioxidant activity that is favorable for promoting antitumor immunity. In the mouse model of OSCC with bacterial infection, PNIPAM/DL@TIR not only ablated the primary tumors upon NIR laser irradiation, but also induced tumor and bacterial vaccination in situ to suppress distant tumors and lung metastasis.

11.
Nanomaterials (Basel) ; 14(13)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38998714

RESUMEN

Chemical warfare agents primarily comprise organophosphorus nerve agents, saliva alkaloids, cyanides, and mustard gas. Exposure to these agents can result in severe respiratory effects, including spasms, edema, and increased secretions leading to breathing difficulties and suffocation. Protecting public safety and national security from such threats has become an urgent priority. Porous metal-organic framework (MOF) materials have emerged as promising candidates for the degradation of chemical warfare agents due to their large surface area, tunable pore size distribution, and excellent catalytic performance. Furthermore, combining MOFs with polymers can enhance their elasticity and processability and improve their degradation performance. In this review, we summarize the literature of the past five years on MOF-based composite materials and their effectiveness in degrading chemical warfare agents. Moreover, we discuss key factors influencing their degradation efficiency, such as MOF structure, pore size, and functionalization strategies. Furthermore, we highlight recent developments in the design of MOF-polymer composites, which offer enhanced degradation performance and stability for practical applications in CWA degradation. These composite materials exhibit good performance in degrading chemical warfare agents, playing a crucial role in protecting public safety and maintaining national security. We can expect to see more breakthroughs in the application of metal-organic framework porous materials for degrading chemical warfare agents. It is hoped that these innovative materials will play a positive role in achieving social stability and security.

12.
J Microbiol Methods ; 224: 106990, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39004285

RESUMEN

The pUC-derived plasmid yield from E. coli using polypropylene tubes (PP) was compared among round and conical tubes. The yield from cells grown in a cheaper conical-PP with flat-bottom was 1.5-fold higher (p < 0.001) than other PP. The use of the conical-PP can save research budgets in the current inflationary environment.

13.
JAMA Netw Open ; 7(7): e2422454, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39028670

RESUMEN

Importance: Diagnosing solid lesions in the pancreas via endoscopic ultrasonographic (EUS) images is challenging. Artificial intelligence (AI) has the potential to help with such diagnosis, but existing AI models focus solely on a single modality. Objective: To advance the clinical diagnosis of solid lesions in the pancreas through developing a multimodal AI model integrating both clinical information and EUS images. Design, Setting, and Participants: In this randomized crossover trial conducted from January 1 to June 30, 2023, from 4 centers across China, 12 endoscopists of varying levels of expertise were randomly assigned to diagnose solid lesions in the pancreas with or without AI assistance. Endoscopic ultrasonographic images and clinical information of 439 patients from 1 institution who had solid lesions in the pancreas between January 1, 2014, and December 31, 2022, were collected to train and validate the joint-AI model, while 189 patients from 3 external institutions were used to evaluate the robustness and generalizability of the model. Intervention: Conventional or AI-assisted diagnosis of solid lesions in the pancreas. Main Outcomes and Measures: In the retrospective dataset, the performance of the joint-AI model was evaluated internally and externally. In the prospective dataset, diagnostic performance of the endoscopists with or without the AI assistance was compared. Results: The retrospective dataset included 628 patients (400 men [63.7%]; mean [SD] age, 57.7 [27.4] years) who underwent EUS procedures. A total of 130 patients (81 men [62.3%]; mean [SD] age, 58.4 [11.7] years) were prospectively recruited for the crossover trial. The area under the curve of the joint-AI model ranged from 0.996 (95% CI, 0.993-0.998) in the internal test dataset to 0.955 (95% CI, 0.940-0.968), 0.924 (95% CI, 0.888-0.955), and 0.976 (95% CI, 0.942-0.995) in the 3 external test datasets, respectively. The diagnostic accuracy of novice endoscopists was significantly enhanced with AI assistance (0.69 [95% CI, 0.61-0.76] vs 0.90 [95% CI, 0.83-0.94]; P < .001), and the supplementary interpretability information alleviated the skepticism of the experienced endoscopists. Conclusions and Relevance: In this randomized crossover trial of diagnosing solid lesions in the pancreas with or without AI assistance, the joint-AI model demonstrated positive human-AI interaction, which suggested its potential to facilitate a clinical diagnosis. Nevertheless, future randomized clinical trials are warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT05476978.


Asunto(s)
Inteligencia Artificial , Estudios Cruzados , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Endosonografía/métodos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/diagnóstico por imagen , Adulto , Páncreas/diagnóstico por imagen , China , Estudios Retrospectivos
14.
Food Chem ; 460(Pt 1): 140424, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39033636

RESUMEN

This work investigated the effects of five thawing methods (air thawing (AT), water thawing (WT), plasma-activated water thawing (PT), ultrasound-assisted water thawing (UWT) and ultrasound-assisted plasma-activated water thawing (UPT)) on thawing rate, quality characteristics, lipid and protein oxidation of porcine longissimus dorsi using fresh sample as control. The thawing time of UPT samples was significantly reduced by 81.15% compared to AT treatment (P < 0.05). The thawing loss of UPT samples was 1.55% significantly lower than AT samples (4.51%) (P < 0.05). In addition, UPT samples had the least cooking loss and centrifugal loss. UPT treatment reduced the conversion of bound and immobilized water to free water and resulted in more uniform water distribution. UPT treatment significantly decreased the thiobarbituric acid reactive substances (TBARS) value and carbonyl content and increased the total sulfhydryl content of the samples (P < 0.05). In conclusion, UPT treatment increased the thawing rate and retarded the lipid and protein oxidation, resulting in better maintenance of quality characteristics of porcine longissimus dorsi than other thawing methods.

15.
J Sep Sci ; 47(14): e2400003, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39034895

RESUMEN

Furosemide (FUR), banned in sports events by the World Anti-Doping Agency, is a key target in drug tests, necessitating a pretreatment material capable of selectively, rapidly, and sufficiently separating/enriching analytes from complex matrices. Herein, a metal-mediated magnetic molecularly imprinted polymer (mMIP) was rationally designed and synthesized for the specific capture of FUR. The preparations involved the utilization of chromium (III) as the binding pivot, (3-aminopropyl)triethoxysilane as functional monomer, and Fe3O4 as core, all assembled via free radical polymerization. Both the morphologies and adsorptive properties of the mMIP were characterized using multiple methods. The resulting Cr(III)-mediated mMIP (ChM-mMIP) presented excellent selectivity and specificity toward FUR. Under optimized conditions, the adsorption capacity reached 128.50 mg/g within 10 min, and the imprinting factor was 10.41. Moreover, it was also successfully applied as a dispersive solid-phase extraction material, enabling the detection of FUR concentration as low as 20 ng/mL in human urine samples when coupled with a high-performance liquid chromatography/photodiode array. Overall, this study offers a valuable strategy for the development of novel recognition material.


Asunto(s)
Furosemida , Polímeros Impresos Molecularmente , Humanos , Furosemida/orina , Furosemida/química , Polímeros Impresos Molecularmente/química , Adsorción , Impresión Molecular , Extracción en Fase Sólida , Propiedades de Superficie , Cromatografía Líquida de Alta Presión , Tamaño de la Partícula , Doping en los Deportes/prevención & control , Polímeros/química , Polímeros/síntesis química
16.
ACS Nano ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39018483

RESUMEN

Neovascular age-related macular degeneration (AMD), a leading cause of blindness, requires frequent intravitreal injection of antivascular endothelial growth factor (anti-VEGF), which could generate a succession of complications with poor patient compliance. The current VEGF-targeting therapies often fail in half of patients due to the complex pathologic microenvironment of excessive reactive oxygen species (ROS) production, and increased levels of inflammation are accompanied by choroidal neovascularization (CNV). We herein reported multifunctional nanotherapeutics featuring superior antioxidant and anti-inflammation properties that aim to reverse the pathological condition, alongside its strong targeted antiangiogenesis to CNV and its ability to provide long-term sustained bioactive delivery via the minimally invasive subconjunctival injection, so as to achieve satisfactory wet AMD treatment effects. Concretely, the nanomedicine was designed by coencapsulation of astaxanthin (AST), a red pigmented carotenoid known for its antioxidative, anti-inflammatory and antiapoptotic properties, and axitinib (AXI), a small molecule tyrosine kinase inhibitor that selectively targets the vascular epidermal growth factor receptor for antiangiogenesis, into the Food and Drug Administration (FDA) approved poly(lactic-co-glycolic acid) (PLGA), which forms the nanodrug of PLGA@AST/AXI. Our results demonstrated that a single-dose subconjunctival administration of PLGA@AST/AXI showed a rational synergistic effect by targeting various prevailing risk factors associated with wet AMD, ensuring persistent drug release profiles, maintaining good ocular biocompatibility, and causing no obvious mechanical damage. Such attributes are vital and hold significant potential in treating ocular posterior segment diseases. Moreover, this nanotherapeutic strategy represents a versatile and broad-spectrum nanoplatform, offering a promising alternative for the complex pathological progression of other neovascular diseases.

17.
Mar Pollut Bull ; 206: 116677, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39018823

RESUMEN

The relative importance of each sediment physicochemical property to sediment heavy-metal (HM) contents has not yet been quantitatively evaluated. Differences in the HM contents of mangrove surface sediments among the high, middle, and low intertidal zones, and their quantitative relationships to sediment physicochemical properties, were investigated in Dongzhaigang and Qinglan Harbor reserves, Hainan, China. In both reserves, the Cu and Ni concentrations increased significantly from the low to high intertidal zones; the patterns of change in the Mn and Pb contents were opposite in the two reserves. The Cr concentration was significantly lower and the Pb concentration was significantly higher in the dry season than in the wet season. Ecological risks of HM were higher in Dongzhaigang than in Qinglan Harbor. Regression and redundancy (hierarchical partitioning) analyses showed that the sediment total sulfur, nitrogen and potassium contents and pH were key factors affecting the HM contents of mangrove surface sediments.

18.
Artículo en Inglés | MEDLINE | ID: mdl-39020253

RESUMEN

BACKGROUND AND HYPOTHESIS: The association between superimposed preeclampsia and an elevated risk of long-term kidney function decline or end-stage kidney disease (ESKD) in patients with chronic kidney disease (CKD) has not been determined. This study aimed to analyze the association between preeclampsia and kidney function deterioration in CKD patients. METHODS: This was a retrospective cohort study that included the clinical information of 103 pregnant CKD patients with preeclampsia and 103 matched CKD patients without preeclampsia who were followed-up for a minimum of 1 year after their first pregnancy from January 1, 2009, to May 31, 2022. Robust Cox regression analysis was also conducted to evaluate the effects of preeclampsia on long-term kidney function decline or ESKD in CKD patients. K-M curves were used to compare renal survival within different subgroups via the log-rank test. RESULTS: During the follow-up period, 44 (42.72%) CKD patients with preeclampsia and 20 (19.42%) without preeclampsia had an estimated glomerular filtration rate (eGFR) decrease >30% or developed ESKD. Compared with CKD patients without preeclampsia, the eGFR decreased more significantly in patients with preeclampsia [98.43 (79.48, 116.47) to 81.32 (41.20, 102.97) mL/min/1.73 m2 vs. 99.43 (79.00, 118.50) to 89.44 (63.69, 105.30) mL/min/1.73 m2; P=0.034]. The rate of eGFR decrease was more pronounced in patients with preeclampsia (17.38% vs. 10.05%, p<0.05). Multivariate analysis revealed that early-onset preeclampsia (preeclampsia that developed before 34 weeks of gestation) (HR=2.61, 95% CI=1.32-5.16, P=0.006) and late-onset preeclampsia (HR=2.54, 95% CI=1.34-4.83, P=0.004) were both risk factors for an eGFR decrease >30% or ESKD. CONCLUSION: Preeclampsia was associated with a greater risk of long-term kidney function decline or ESKD among CKD patients, especially in patients with early-onset preeclampsia.

19.
BMC Pulm Med ; 24(1): 343, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014333

RESUMEN

BACKGROUND: Primary ciliary dyskinesia (PCD) is an autosomal recessive hereditary disease characterized by recurrent respiratory infections. In clinical manifestations, DNAH5 (NM_001361.3) is one of the recessive pathogenic genes. Primary familial brain calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcification in the basal ganglia and other brain regions. PFBC can be inherited in an autosomal dominant or recessive manner. A family with PCD caused by a DNAH5 compound heterozygous variant and PFBC caused by a MYORG homozygous variant was analyzed. METHODS: In this study, we recruited three generations of Han families with primary ciliary dyskinesia combined with primary familial brain calcification. Their clinical phenotype data were collected, next-generation sequencing was performed to screen suspected pathogenic mutations in the proband and segregation analysis of families was carried out by Sanger sequencing. The mutant and wild-type plasmids were constructed and transfected into HEK293T cells instantaneously, and splicing patterns were detected by Minigene splicing assay. The structure and function of mutations were analyzed by bioinformatics analysis. RESULTS: The clinical phenotypes of the proband (II10) and his sister (II8) were bronchiectasis, recurrent pulmonary infection, multiple symmetric calcifications of bilateral globus pallidus and cerebellar dentate nucleus, paranasal sinusitis in the whole group, and electron microscopy of bronchial mucosa showed that the ciliary axoneme was defective. There was also total visceral inversion in II10 but not in II8. A novel splice variant C.13,338 + 5G > C and a frameshift variant C.4314delT (p. Asn1438lysfs *10) were found in the DNAH5 gene in proband (II10) and II8. c.347_348dupCTGGCCTTCCGC homozygous insertion variation was found in the MYORG of the proband. The two pathogenic genes were co-segregated in the family. Minigene showed that DNAH5 c.13,338 + 5G > C has two abnormal splicing modes: One is that part of the intron bases where the mutation site located is translated, resulting in early translation termination of DNAH5; The other is the mutation resulting in the deletion of exon76. CONCLUSIONS: The newly identified DNAH5 splicing mutation c.13,338 + 5G > C is involved in the pathogenesis of PCD in the family, and forms a compound heterozygote with the pathogenic variant DNAH5 c.4314delT lead to the pathogenesis of PCD.


Asunto(s)
Calcinosis , Mutación , Linaje , Humanos , Masculino , Calcinosis/genética , Calcinosis/patología , Femenino , Dineínas Axonemales/genética , Adulto , Trastornos de la Motilidad Ciliar/genética , Encefalopatías/genética , Fenotipo , Células HEK293 , China , Empalme del ARN/genética , Persona de Mediana Edad , Glicósido Hidrolasas
20.
Food Chem ; 459: 140430, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39024870

RESUMEN

This study evaluated the effects of five thawing methods (air thawing (AT), water thawing (WT), plasma-activated water thawing (PT), ultrasound-assisted water thawing (UWT) and ultrasound-assisted plasma-activated water thawing (UPT)) on the physicochemical, thermal stability, rheological, and structural properties of porcine longissimus dorsi myofibrillar protein (MP). UPT treatment significantly improved protein solubility (73.10%) and reduced protein turbidity (0.123) compared with AT, WT, and PT treatments (P < 0.05). UPT treatment reduced the MP particle size (635.50 nm) and zeta potential (-6.38 mV) compared with AT and WT treatments (P < 0.05), which was closer to that of the fresh sample. UPT treatment also maintained the MP surface hydrophobicity and thermal stability. UPT treatment improved the MP rheological properties of the sample. In addition, UPT treatment effectively protected the MP secondary and tertiary structures. In conclusion, UPT treatment better maintained the MP physicochemical, thermal stability, rheological, and structural properties of thawed porcine longissimus dorsi. Therefore, UPT treatment can be considered as an effective thawing method.

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