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1.
Inorg Chem ; 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39312639

RESUMEN

Palladium (Pd) capture from high-level liquid waste for subsequent photocatalytic applications is desirable for the development of nuclear energy and the reutilization of valuable resources. Herein, we approach our design with a unique porous organic polymer containing thiazolo[5,4-d]thiazole units (denoted as TzPOP-OH). It possesses two potential soft-hard (N-O and S-O) combined coordination sites for Pd(II) coordination and features strong donor-acceptor repeating units and high planarity of linkage enforced by hydrogen bonds for subsequent photocatalysis. Accordingly, TzPOP-OH with three hydroxyl groups on the linkage exhibits a high Pd(II) capacity of 369 mg g-1 at 3 M HNO3, considerably surpassing those of the controlled polymer TzPOP without hydroxyl groups and most other reported materials. Additionally, TzPOP-OH boasts other merits, including outstanding acid tolerance, extraordinary radiation stability, good reusability, and remarkable selectivity. After palladium adsorption, Pd@TzPOP-OH demonstrates impressive photodegradation efficiency to reduce the concentration of rhodamine B in contaminated urban water from 10 to less than 0.1 ppm. This work provides a feasible approach to designing materials with both suitable coordination microenvironments and semiconductor properties for metal separation and photocatalysis.

2.
Biochem Biophys Res Commun ; 734: 150740, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39342798

RESUMEN

BACKGROUND: Psoriasis, characterized by chronic inflammation, is a persistent skin condition that is notoriously challenging to manage and prone to relapse. Despite significant advancements in its treatment, many adverse reactions still occur. Therefore, exploring the mechanisms behind the occurrence and development of psoriasis is extremely important. METHODS: The weighted correlation network analysis (WGCNA) algorithm was used to identify phenotype-related genes in patients with psoriasis. We recruited clinical samples of patients with psoriasis, and used single-cell RNA sequencing (scRNA-seq) to visualize divergent genes and metabolisms of varied cells for the psoriasis. Various machine-learning methods were used to identify core genes, and molecular docking was used to analyze the stability of leptomycin B targeting pituitary tumor transforming 1 (PTTG1). Immunofluorescence (IHC) analysis, multiplex immunofluorescence (mIF) analysis, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to validate the results. RESULTS: Our results identified 1391 genes associated with the phenotype in patients with psoriasis and highlighted the significant alterations in T-cell functionality observed in the disease by WGCNA. There were nine distinct cellular clusters in psoriasis analyzed with the aid of scRNA-seq data. Each subtype of cell exhibited distinct genetic profiles, functional roles, signaling mechanisms, and metabolic characteristics. Machine-learning methods further demonstrated the potential diagnostic value of T cell-derived PTTG1 and its relationship with T-cell exhaustion in psoriasis. Lastly, the leptomycin B was scrutinized and verified had high stability targeting PTTG1. CONCLUSIONS: This study elucidates the biological basis of psoriasis. At the same time, it was discovered that PTTG1 derived from exhausted T cells serves as a diagnostic biomarker for psoriasis. Leptomycin B could be a potential drug for targeted treatment of psoriasis on PTTG1.

3.
Sensors (Basel) ; 24(18)2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39338876

RESUMEN

Anomaly detection in industrial control system (ICS) data is one of the key technologies for ensuring the security monitoring of ICSs. ICS data are characterized as complex, multi-dimensional, and long-sequence time-series data that embody ICS business logic. Due to its complex and varying periodic characteristics, as well as the presence of long-distance and misaligned temporal associations among features, current anomaly detection methods in ICS are insufficient for feature extraction. This paper proposes an anomaly detection method named TFANet, based on time-frequency fusion feature attention encoding. Considering that periodic variations are more concentrated in the frequency domain, this method first transforms the time-domain data into the frequency domain, obtaining both amplitude and phase data. Then, these data, together with the original time-series data, are used to extract features from two perspectives: long-term temporal changes and long-distance associations. Finally, the six features learned from both the time and frequency domains are fused, and the feature weights are calculated using an attention mechanism to complete the anomaly classification. In multi-classification tasks on three ICS datasets, the proposed method outperforms three popular time-series models-iTransformer, Crossformer, and TimesNet-across five metrics: accuracy, precision, recall, F1 score, and AUC-ROC, with average improvements of approximately 19%, 37%, 31%, 35%, and 22%, respectively.

5.
Front Psychiatry ; 15: 1431837, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39319359

RESUMEN

Introduction: Hyperarousal has been a significant pathophysiological theory related to insomnia disorder (ID), characterized by excessive cortical activation and abnormal electroencephalogram (EEG) power during daytime or sleep. However, there is currently insufficient attention to the EEG power during rapid eye movement (REM) sleep and different stages of non-rapid eye movement (NREM) sleep. Additionally, whether the abnormal sleep EEG power in ID patients can be restored by repetitive transcranial magnetic stimulation (rTMS) remains unclear. Methods>: Data of 26 ID patients and 26 healthy controls (HCs) were included in the current observational study. The comparisons of relative power between patients and HCs at baseline in each band of each sleep stage and the changes in patients before and after rTMS treatment were performed. The correlations between relative power and behavioral measures of the patients were also investigated. Results: Abnormalities in sleep EEG relative power in the delta, beta and gamma bands of the patients were observed in NREM2, NREM3 and REM sleep. Correlations were identified between relative power and behavioral measures in ID group, primarily encompassing sleep efficiency, sleep onset latency and depression scores. Post-treatment improvements in relative power of the delta and beta band were observed in NREM2 sleep. Discussion: The relative power of sleep EEG exhibited a significant correlation with sleep measures in ID patients, and demonstrated notable differences from HCs across the delta, beta, and gamma frequency bands. Furthermore, our findings suggest that rTMS treatment may partially ameliorate relative power abnormalities in patients with ID.

6.
Int J Nurs Stud ; 160: 104910, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39303641

RESUMEN

BACKGROUND: Parental cancer conditions significantly impact the physical, social, and emotional well-being of minor children. Effective illness-related communication is crucial for both parents and their children to mitigate these effects. OBJECTIVE: To systematically summarize the characteristics and effectiveness of interventions aimed at improving illness-related communication between parents with cancer and their minor children. DESIGN: A systematic review. DATA SOURCES: Six databases (CINAHL, Web of Science, PubMed, Embase, the Cochrane Library, and PsycINFO) were searched for articles published in English between 2000 and 2023. METHODS: A three-step review process was employed to select articles. Two reviewers independently screened titles and abstracts, reviewed full texts to include studies aimed at facilitating illness-related communication between parents with cancer and their minor children under the age of 18, and assessed study quality using the Joanna Briggs Institute critical appraisal checklist. RESULTS: The search yielded 9409 articles, of which 21 met the inclusion criteria, 4 were randomized controlled trials and 17 were quasi-experimental studies. These studies involved 213 families, 149 parents, and 192 minor children. The interventions were categorized as family-centered, parent-centered, or children-centered and emphasized disease knowledge, communication skills, emotional management, and future planning in illness-related communication. The synthesized results indicate that family-centered interventions show unique advantages in improving family life; parent-centered interventions bring benefits in enhancing parenting quality, parents' self-efficacy in coping with cancer, and children's social behavior; and children-centered interventions exhibit a significant impact on the psychological well-being of children. CONCLUSION: Parent-centered interventions demonstrated significant potential in promoting illness-related communication, particularly by emphasizing the patient's parental role, enhancing intrinsic motivation to sustain communication, and recognizing that patients themselves may be more suitable targets for clinical oncology practice. High-quality research is recommended to enrich the content of parent-centered interventions and encourage the measurement of intervention effects on communication as well as the mechanism of action. REGISTRATION NUMBER: The review protocol was registered in PROSPERO under the number CRD42023478107.

7.
Abdom Radiol (NY) ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39299988

RESUMEN

OBJECTIVE: To comprehensively evaluate the renal structure and function of patients with renal artery stenosis (RAS) using multiparametric magnetic resonance imaging (MRI), and analyze the correlation between magnetic resonance (MR) parameters and renal function. MATERIALS AND METHODS: Renal multiparametric MRI was conducted on 62 patients with RAS utilizing a Philips Ingenia CX 3.0 T MRI system. The scanning protocols encompassed arterial spin labeling, phase contrast MRI, diffusion weighted imaging, T1 mapping, and blood oxygen level-dependent MRI. All patients underwent radionuclide renal dynamic imaging to calculate the glomerular filtration rate (GFR) for assessing renal function. RESULTS: Most MR parameters were correlated with GFR: renal parenchymal volume (R = 0.603), whole kidney renal blood flow (RBF) (R = 0.192), renal cortical RBF (R = 0.294), renal artery mean velocity (R = 0.593), stroke volume (R = 0.599), mean flux (R = 0.629), renal cortical apparent diffusion coefficient (ADC) (R = 0.466), medullary ADC (R = 0.332), cortical T1 value (R = - 0.206), corticomedullary T1 difference (R = 0.204), cortical T2* value (R = 0.448), and medullary T2* value (R = 0.272). The best prediction model for GFR using multiparametric MRI was obtained, including renal PV, whole kidney RBF, cortical RBF, mean velocity, mean flux, and CMD T1. CONCLUSION: Multiparametric MRI is a novel noninvasive examination method that can effectively and comprehensively assess the renal structure and function of RAS.

8.
Sci Rep ; 14(1): 21410, 2024 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271781

RESUMEN

Acute ischemic stroke (AIS) is a major global health concern due to its high mortality and disability rates. Hemorrhagic transformation, a common complication of AIS, leads to poor prognosis yet lacks effective treatments. Preclinical studies indicate that hyperbaric oxygen (HBO) treatment within 12 h of AIS onset alleviates ischemia/reperfusion injuries, including hemorrhagic transformation. However, clinical trials have yielded conflicting results, suggesting some underlying mechanisms remain unclear. In this study, we confirmed that HBO treatments beginning within 1 h post reperfusion significantly alleviated the haemorrhage and neurological deficits in hyperglycemic transient middle cerebral arterial occlusion (tMCAO) mice, partly due to the inhibition of the NLRP3 inflammasome-mediated pro-inflammatory response in microglia. Notably, reactive oxygen species (ROS) mediate the anti-inflammatory and protective effect of early HBO treatment, as edaravone and N-Acetyl-L-Cysteine (NAC), two commonly used antioxidants, reversed the suppressive effect of HBO treatment on NLRP3 inflammasome-mediated inflammation in microglia. Furthermore, NAC countered the protective effect of early HBO treatment in tMCAO mice with hyperglycemia. These findings support that early HBO treatment is a promising intervention for AIS, however, caution is warranted when combining antioxidants with HBO treatment. Further assessments are needed to clarify the role of antioxidants in HBO therapy for AIS.


Asunto(s)
Oxigenoterapia Hiperbárica , Hiperglucemia , Microglía , Especies Reactivas de Oxígeno , Animales , Microglía/metabolismo , Microglía/efectos de los fármacos , Oxigenoterapia Hiperbárica/métodos , Ratones , Especies Reactivas de Oxígeno/metabolismo , Hiperglucemia/metabolismo , Hiperglucemia/complicaciones , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Modelos Animales de Enfermedad , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/metabolismo , Antioxidantes/farmacología , Ratones Endogámicos C57BL , Infarto de la Arteria Cerebral Media/terapia , Edaravona/farmacología , Daño por Reperfusión/metabolismo
9.
Biomacromolecules ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259212

RESUMEN

Glioblastoma multiforme (GBM) is a highly malignant brain tumor with a poor prognosis and limited treatment options. Drug delivery by stimuli-responsive nanocarriers holds great promise for improving the treatment modalities of GBM. At the beginning of the review, we highlighted the stimuli-active polymeric nanocarriers carrying therapies that potentially boost anti-GBM responses by employing endogenous (pH, redox, hypoxia, enzyme) or exogenous stimuli (light, ultrasonic, magnetic, temperature, radiation) as triggers for controlled drug release mainly via hydrophobic/hydrophilic transition, degradability, ionizability, etc. Modifying these nanocarriers with target ligands further enhanced their capacity to traverse the blood-brain barrier (BBB) and preferentially accumulate in glioma cells. These unique features potentially lead to more effective brain cancer treatment with minimal adverse reactions and superior therapeutic outcomes. Finally, the review summarizes the existing difficulties and future prospects in stimuli-responsive nanocarriers for treating GBM. Overall, this review offers theoretical guidelines for developing intelligent and versatile stimuli-responsive nanocarriers to facilitate precise drug delivery and treatment of GBM in clinical settings.

10.
Proc Natl Acad Sci U S A ; 121(37): e2403421121, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39226350

RESUMEN

Drug-resistant Tuberculosis (TB) is a global public health problem. Resistance to rifampicin, the most effective drug for TB treatment, is a major growing concern. The etiological agent, Mycobacterium tuberculosis (Mtb), has a cluster of ATP-binding cassette (ABC) transporters which are responsible for drug resistance through active export. Here, we describe studies characterizing Mtb Rv1217c-1218c as an ABC transporter that can mediate mycobacterial resistance to rifampicin and have determined the cryo-electron microscopy structures of Rv1217c-1218c. The structures show Rv1217c-1218c has a type V exporter fold. In the absence of ATP, Rv1217c-1218c forms a periplasmic gate by two juxtaposed-membrane helices from each transmembrane domain (TMD), while the nucleotide-binding domains (NBDs) form a partially closed dimer which is held together by four salt-bridges. Adenylyl-imidodiphosphate (AMPPNP) binding induces a structural change where the NBDs become further closed to each other, which downstream translates to a closed conformation for the TMDs. AMPPNP binding results in the collapse of the outer leaflet cavity and the opening of the periplasmic gate, which was proposed to play a role in substrate export. The rifampicin-bound structure shows a hydrophobic and periplasm-facing cavity is involved in rifampicin binding. Phospholipid molecules are observed in all determined structures and form an integral part of the Rv1217c-1218c transporter system. Our results provide a structural basis for a mycobacterial ABC exporter that mediates rifampicin resistance, which can lead to different insights into combating rifampicin resistance.


Asunto(s)
Transportadoras de Casetes de Unión a ATP , Proteínas Bacterianas , Microscopía por Crioelectrón , Farmacorresistencia Bacteriana , Mycobacterium tuberculosis , Rifampin , Rifampin/farmacología , Rifampin/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Transportadoras de Casetes de Unión a ATP/química , Transportadoras de Casetes de Unión a ATP/ultraestructura , Transportadoras de Casetes de Unión a ATP/genética , Mycobacterium tuberculosis/metabolismo , Mycobacterium tuberculosis/efectos de los fármacos , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/ultraestructura , Proteínas Bacterianas/genética , Modelos Moleculares , Adenilil Imidodifosfato/metabolismo
11.
Dalton Trans ; 53(36): 15316-15323, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39224067

RESUMEN

Two o-carborane-hybridized macrocyclic arenes have been synthesized via Friedel-Crafts alkylation of carborane diaryl derivatives. The single-crystal X-ray diffraction analysis clearly revealed their cavity structure and intermolecular interaction force. These novel macrocycles exhibited aggregation-induced luminescence and intramolecular charge transfer properties and also significant selectivity towards nitro explosive compounds. This work provided a method for the synthesis of hybridized macrocyclic arenes.

12.
PeerJ ; 12: e17974, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39308825

RESUMEN

The sugars will eventually be exported transporter (SWEET) family is a novel class of sugar transporters that play a crucial role in plant growth, development, and responses to stress. Cranberry (Vaccinium macrocarpon Ait.) is a nutritious berry with economic importance, but little is known about SWEET gene family functions in this small fruit. In this research, 13 VmSWEET genes belonging to four clades were identified in the cranberry genome for the first time. In the conserved domains, we observed seven phosphorylation sites and four amino acid residues that might be crucial for the binding function. The majority of VmSWEET genes in each clade shared similar gene structures and conserved motifs, showing that the VmSWEET genes were highly conserved during evolution. Chromosomal localization and duplication analyses showed that VmSWEET genes were unevenly distributed in eight chromosomes and two pairs of them displayed synteny. A total of 79 cis-acting elements were predicted in the promoter regions of VmSWEETs including elements responsive to plant hormones, light, growth and development and stress responses. qRT-PCR analysis showed that VmSWEET10.1 was highly expressed in flowers, VmSWEET16 was highly expressed in upright and runner stems, and VmSWEET3 was highly expressed in the leaves of both types of stems. In fruit, the expression of VmSWEET14 and VmSWEET16 was highest of all members during the young fruit stage and were downregulated as fruit matured. The expression of VmSWEET4 was higher during later developmental stages than earlier developmental stages. Furthermore, qRT-PCR results revealed a significant up-regulation of VmSWEET10.2, under osmotic, saline, salt-alkali, and aluminum stress conditions, suggesting it has a crucial role in mediating plant responses to various environmental stresses. Overall, these results provide new insights into the characteristics and evolution of VmSWEET genes. Moreover, the candidate VmSWEET genes involved in the growth, development and abiotic stress responses can be used for molecular breeding to improve cranberry fruit quality and abiotic stress resistance.


Asunto(s)
Frutas , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Estrés Fisiológico , Vaccinium macrocarpon , Vaccinium macrocarpon/genética , Vaccinium macrocarpon/metabolismo , Vaccinium macrocarpon/química , Estrés Fisiológico/genética , Frutas/genética , Frutas/crecimiento & desarrollo , Frutas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Familia de Multigenes , Proteínas de Transporte de Monosacáridos/genética , Proteínas de Transporte de Monosacáridos/metabolismo , Filogenia , Genoma de Planta , Desarrollo de la Planta/genética , Cromosomas de las Plantas/genética , Sintenía/genética
13.
Int J Mol Sci ; 25(18)2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39337329

RESUMEN

Gene expression is orchestrated by a complex array of gene regulatory elements that govern transcription in a cell-type-specific manner. Though previously studied, the ability to utilize regulatory elements to identify disrupting variants remains largely elusive. To identify important factors within these regions, we generated enhancer-promoter interaction (EPI) networks and investigated the presence of disease-associated variants that fall within these regions. Our study analyzed six neuronal cell types across neural differentiation, allowing us to examine closely related cell types and across differentiation stages. Our results expand upon previous findings of cell-type specificity of enhancer, promoter, and transcription factor binding sites. Notably, we find that regulatory regions within EPI networks can identify the enrichment of variants associated with neuropsychiatric disorders within specific cell types and network sub-structures. This enrichment within sub-structures can allow for a better understanding of potential mechanisms by which variants may disrupt transcription. Together, our findings suggest that EPIs can be leveraged to better understand cell-type-specific regulatory architecture and used as a selection method for disease-associated variants to be tested in future functional assays. Combined with these future functional characterization assays, EPIs can be used to better identify and characterize regulatory variants' effects on such networks and model their mechanisms of gene regulation disruption across different disorders. Such findings can be applied in practical settings, such as diagnostic tools and drug development.


Asunto(s)
Elementos de Facilitación Genéticos , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Regiones Promotoras Genéticas , Humanos , Transcripción Genética , Neuronas/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Diferenciación Celular/genética , Sitios de Unión
14.
ACS Appl Mater Interfaces ; 16(33): 44127-44138, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39119797

RESUMEN

The repair of large bone defects poses a significant challenge in orthopedics. Polyetheretherketone (PEEK) is a promising bone substitute, while it suffers a lack of bioactivity. Although several studies have been performed to further improve the bioactivities of PEEK by various surface modifications, PEEK offering long-term, multifaceted biofunctionalities remains still desired. In this study, we introduced metal-organic frameworks (MOFs), specifically ZIF-8 loaded with celecoxib (ZIF-8(CEL)), onto the PEEK surface through dopamine adhesion. The resulting PEEK@ZIF-8(CEL) aims to achieve long-term stable release of Zn ions and CEL for enhanced bone integration. Material characterization and biological experiments confirmed the successful integration of ZIF-8(CEL) onto PEEK and its positive biomedical effects, including creating a positive bone immunological environment and promoting bone growth. This study demonstrates the potential of PEEK@ZIF-8(CEL) as a novel repair material for large bone defects, offering a promising alternative in orthopedic applications.


Asunto(s)
Benzofenonas , Cetonas , Polietilenglicoles , Polímeros , Benzofenonas/química , Polímeros/química , Cetonas/química , Polietilenglicoles/química , Animales , Ratones , Estructuras Metalorgánicas/química , Sustitutos de Huesos/química , Sustitutos de Huesos/uso terapéutico , Sustitutos de Huesos/farmacología , Zinc/química , Osteogénesis/efectos de los fármacos
15.
Ecotoxicol Environ Saf ; 284: 116896, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39159541

RESUMEN

The Guangdong, Hong Kong, and Macao Greater Bay Area (GHMA) has experienced economic development and rapid growth of transportation infrastructure in recent years. However, the economic advancement is also accompanied by serious atmospheric pollution, which threatens the health of the residents, thus, it is of great significance to explore the impact of atmospheric pollution on the health expenditures of residents in the GHMA. The article establishes a spatial econometric model to study the impact of atmospheric pollution on residents' health expenditure in the GHMA based on panel data from 2014 to 2021, using nine prefectures in the GHMA as research objects. The results show that: (1) Atmospheric pollution in the GHMA has an obvious spatial agglomeration phenomenon and spatial spillover effect, and the impact of atmospheric pollution on the health of the residents is still very serious; (2) PM2.5 emissions are positively and significantly related to the actual health care cost per person, and the rise in air pollution is the main reason for the rise in public health spending; (3) Other factors also have different impacts on residents' health expenditures. Based on the above research, the article puts forward corresponding policy recommendations.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Gastos en Salud , Material Particulado , Hong Kong , Material Particulado/análisis , Humanos , Contaminantes Atmosféricos/análisis , China , Macao , Bahías , Monitoreo del Ambiente , Modelos Econométricos , Exposición a Riesgos Ambientales
16.
Cell Death Dis ; 15(8): 600, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39160159

RESUMEN

Crizotinib carries an FDA hepatotoxicity warning, yet analysis of the FAERS database suggests that the severity of its hepatotoxicity risks, including progression to hepatitis and liver failure, might be underreported. However, the underlying mechanism remains poorly understood, and effective intervention strategies are lacking. Here, mRNA-sequencing analysis, along with KEGG and GO analyses, revealed that DEGs linked to Crizotinib-induced hepatotoxicity predominantly associate with the ferroptosis pathway which was identified as the principal mechanism behind Crizotinib-induced hepatocyte death. Furthermore, we found that ferroptosis inhibitors, namely Ferrostatin-1 and Deferoxamine mesylate, significantly reduced Crizotinib-induced hepatotoxicity and ferroptosis in both in vivo and in vitro settings. We have also discovered that overexpression of AAV8-mediated Nrf2 could mitigate Crizotinib-induced hepatotoxicity and ferroptosis in vivo by restoring the imbalance in glutathione metabolism, iron homeostasis, and lipid peroxidation. Additionally, both Stat1 deficiency and the Stat1 inhibitor NSC118218 were found to reduce Crizotinib-induced ferroptosis. Mechanistically, Crizotinib induces the phosphorylation of Stat1 at Ser727 but not Tyr701, promoting the transcriptional inhibition of Nrf2 expression after its entry into the nucleus to promote ferroptosis. Meanwhile, we found that MgIG and GA protected against hepatotoxicity to counteract ferroptosis without affecting or compromising the anti-cancer activity of Crizotinib, with a mechanism potentially related to the Stat1/Nrf2 pathway. Overall, our findings identify that the phosphorylation activation of Stat1 Ser727, rather than Tyr701, promotes ferroptosis through transcriptional inhibition of Nrf2, and highlight MgIG and GA as potential therapeutic approaches to enhance the safety of Crizotinib-based cancer therapy.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Crizotinib , Ferroptosis , Factor 2 Relacionado con NF-E2 , Factor de Transcripción STAT1 , Ferroptosis/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Humanos , Animales , Crizotinib/farmacología , Crizotinib/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT1/genética , Ratones , Transducción de Señal/efectos de los fármacos , Masculino , Fenilendiaminas/farmacología , Ratones Endogámicos C57BL , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacos , Fosforilación/efectos de los fármacos
17.
BMC Med Imaging ; 24(1): 202, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103756

RESUMEN

BACKGROUND: Community-Acquired Pneumonia (CAP) remains a significant global health concern, with a subset of cases progressing to Severe Community-Acquired Pneumonia (SCAP). This study aims to develop and validate a CT-based radiomics model for the early detection of SCAP to enable timely intervention and improve patient outcomes. METHODS: A retrospective study was conducted on 115 CAP and SCAP patients at Southern Medical University Shunde Hospital from January to December 2021. Using the Pyradiomics package, 107 radiomic features were extracted from CT scans, refined via intra-class and inter-class correlation coefficients, and narrowed down using the Least Absolute Shrinkage and Selection Operator (LASSO) regression model. The predictive performance of the radiomics-based model was assessed through receiver operating characteristic (ROC) analysis, employing machine learning classifiers such as k-Nearest Neighbors (KNN), Support Vector Machine (SVM), Logistic Regression (LR), and Random Forest (RF), trained and validated on datasets split 7:3, with a training set (n = 80) and a validation set (n = 35). RESULTS: The radiomics model exhibited robust predictive performance, with the RF classifier achieving superior precision and accuracy compared to LR, SVM, and KNN classifiers. Specifically, the RF classifier demonstrated a precision of 0.977 (training set) and 0.833 (validation set), as well as an accuracy of 0.925 (training set) and 0.857 (validation set), suggesting its superior performance in both metrics. Decision Curve Analysis (DCA) was utilized to evaluate the clinical efficacy of the RF classifier, demonstrating a favorable net benefit within the threshold ranges of 0.1 to 0.8 for the training set and 0.2 to 0.7 for the validation set. CONCLUSIONS: The radiomics model developed in this study shows promise for early SCAP detection and can improve clinical decision-making.


Asunto(s)
Infecciones Comunitarias Adquiridas , Diagnóstico Precoz , Neumonía , Tomografía Computarizada por Rayos X , Humanos , Infecciones Comunitarias Adquiridas/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Femenino , Masculino , Neumonía/diagnóstico por imagen , Persona de Mediana Edad , Anciano , Aprendizaje Automático , Curva ROC , Máquina de Vectores de Soporte , Índice de Severidad de la Enfermedad , Radiómica
18.
Artículo en Inglés | MEDLINE | ID: mdl-39102869

RESUMEN

Community-acquired pneumonia (CAP) is a significant global health concern, responsible for high mortality and morbidity. Recent research has revealed a potential link between disordered microbiome and metabolism in pneumonia, although the precise relationship between these factors and severe CAP remains unclear. To address this knowledge gap, we conducted a comprehensive analysis utilizing 16S sequencing and LC-MS/MS metabolomics data to characterize the microbial profile in sputum and metabolic profile in serum in patients with severe community-acquired pneumonia (sCAP). Our analysis identified 13 genera through LEfSe analysis and 15 metabolites meeting specific criteria (P < 0.05, VIP ≥ 2, and |Log2(FC)| ≥ 2). The findings of this study demonstrate the presence of altered coordination between the microbiome of the lower respiratory tract and host metabolism in patients with sCAP. The observed concentration trends of specific metabolites across different disease stages further support the potential involvement of the serum metabolism in the development of sCAP. These correlations between the airway microbiome and host metabolism in sCAP patients have important implications for optimizing early diagnosis and developing individualized therapeutic strategies.

19.
Sci China Life Sci ; 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39110401

RESUMEN

Increasing evidence suggests that deregulated RNA splicing factors play critical roles in tumorigenesis; however, their specific involvement in colon cancer remains largely unknown. Here we report that the splicing factor RBM25 is overexpressed in colon cancer, and this increased expression correlates with a poor prognosis of patients with colon cancer. Functionally, RBM25 ablation suppresses the growth of colon cancer cells both in vitro and in vivo. Mechanistically, our transcriptome-wide analysis of splicing events revealed that RBM25 regulates a large number of cancer-related alternative splicing events across the human genome in colon cancer. Particularly, RBM25 regulates the splicing of MNK2 by interacting with the poly G rich region in exon 14a, thereby inhibiting the selection of the proximal 3' splice site (ss), resulting in the production of the oncogenic short isoform, MNK2b. Knockdown of RBM25 leads to an increase in the MNK2a isoform and a decrease in the MNK2b isoform. Importantly, re-expression of MNK2b or blocking the 3' ss of the alternative exon 14a with ASO partially reverses the RBM25 knockdown mediated tumor suppression. Moreover, MNK2b levels were significantly increased in colon cancer tissues, which is positively correlated with the expression level of RBM25. Collectively, our findings uncover the critical role of RBM25 as a key splicing factor in colon cancer, suggesting its potential as a prognostic marker and therapeutic target.

20.
Geriatr Nurs ; 59: 471-478, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39141954

RESUMEN

To identify core and bridge nodes in the network structure of alexithymia and cognitive emotion regulation strategies in community-dwelling older adults, and compare network differences among older adults with different health statuses, we recruited 677 participants and network analysis was performed in R 4.2.0. After including the covariates, the nodes Catastrophizing, Difficulty Identifying feelings, and Refocusing on Planning ranked as the top three. The nodes Externally Oriented Thoughts and Difficulty Identifying Feelings were identified as bridge nodes based on bridge strength values. Significant differences were observed between the healthy and comorbidity groups, and also between the single chronic disease and comorbidity groups (p < 0.05). Catastrophizing, Difficulty Identifying Feelings, and Refocusing on Planning were the core nodes, and Externally Oriented Thoughts and Difficulty Identifying Feelings were the key bridge nodes. The network structure of comorbidity in older adults was characterized by stronger ties to non-adaptive cognitive emotion regulation strategies.

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