Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.217
Filtrar
1.
bioRxiv ; 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38826317

RESUMEN

Cancer-associated fibroblasts (CAFs) play a key role in metabolic reprogramming and are well-established contributors to drug resistance in colorectal cancer (CRC). To exploit this metabolic crosstalk, we integrated a systems biology approach that identified key metabolic targets in a data-driven method and validated them experimentally. This process involved high-throughput computational screening to investigate the effects of enzyme perturbations predicted by a computational model of CRC metabolism to understand system-wide effects efficiently. Our results highlighted hexokinase (HK) as one of the crucial targets, which subsequently became our focus for experimental validation using patient-derived tumor organoids (PDTOs). Through metabolic imaging and viability assays, we found that PDTOs cultured in CAF conditioned media exhibited increased sensitivity to HK inhibition. Our approach emphasizes the critical role of integrating computational and experimental techniques in exploring and exploiting CRC-CAF crosstalk.

2.
Carbohydr Polym ; 339: 122174, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38823938

RESUMEN

Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects. In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering. Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications.


Asunto(s)
Regeneración Ósea , Liofilización , Gelatina , Ácido Hialurónico , Hidrogeles , Iridoides , Fibrina Rica en Plaquetas , Animales , Iridoides/química , Iridoides/farmacología , Gelatina/química , Conejos , Hidrogeles/química , Hidrogeles/farmacología , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Regeneración Ósea/efectos de los fármacos , Fibrina Rica en Plaquetas/química , Ingeniería de Tejidos/métodos , Reactivos de Enlaces Cruzados/química , Andamios del Tejido/química , Tibia/efectos de los fármacos , Tibia/cirugía
3.
J Am Geriatr Soc ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38838363

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is a major health issue worldwide. As the population ages, more older patients including octogenarians will require CRC treatment. However, this vulnerable group has decreased functional reserves and increased surgical risks. Enhanced recovery after surgery (ERAS) pathways aim to reduce surgical stress and complications, but concerns remain about applying ERAS protocols to older patients. We assessed whether a modified ERAS (mERAS) protocol combined would improve outcomes in octogenarian CRC patients undergoing minimally invasive surgery. METHODS: In this retrospective cohort study, we compared 360 non-octogenarians aged 50-64 years and 114 octogenarians aged 80-89 years before and after mERAS protocol implementation. Outcomes including postoperative functionary recovery, length of stay, complications, emergency department visits, and readmissions were analyzed. RESULTS: Despite comparable tumor characteristics, octogenarians had poorer nutrition, American Society of Anesthesiologists status, and more comorbidities. After mERAS, octogenarians had reduced complications, faster return of bowel function, and shorter postoperative length of stay, similar to non-octogenarians. mERAS implementation improved recovery in both groups without increasing emergency department visits or readmissions. CONCLUSION: Although less remarkable than in non-octogenarians, mERAS protocols mitigated higher complication rates and improved recovery in octogenarians after minimally invasive surgery for CRC, confirming protocol feasibility and safety in this vulnerable population.

4.
Poult Sci ; 103(7): 103831, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38833958

RESUMEN

The recent emergence of hepatitis-hydropericardium syndrome caused by highly pathogenic fowl adenovirus serotype 4 (FAdV-4) has resulted in significant economic losses to the poultry industry. However, the early innate immune response of immune organs within 24 hpi and the induction of autophagy in vivo after FAdV-4 infection have not been fully elucidated. In this study, 35-day-old specific pathogen-free (SPF) chickens were artificially infected with hypervirulent FAdV-4, which resulted in a mortality rate of up to 90%. The results showed that FAdV-4 infection rapidly triggered the innate immune response in vivo of chickens, with the spleen eliciting a stronger innate immune response than the thymus and bursa. During the early stage of viral infection within 24 hpi, the main receptors TLR3/7/21, MDA5, and cGAS were activated via the NF-κB and TBK1/IRF7-dependent signaling pathways, which up-regulated production of inflammatory cytokines and type I interferons. Additionally, the expression levels of the autophagy-related molecules LC3B, Beclin1, and ATG5 were significantly up-regulated at 24 hpi, while degradation of SQSTM1/p62 was observed, suggesting that FAdV-4 infection elicits a complete autophagy response in the spleen. Besides, the colocalization of Fiber2 and LC3B suggested that FAdV-4 infection induced autophagy which benefits FAdV-4 replication in vivo. This study provides new insights into the immunoregulation signal pathways of the early innate immunity in response to hypervirulent FAdV-4 infection in vivo within 24 hpi and the close relationship between viral replication and autophagy.

5.
Acta Pharmacol Sin ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38834683

RESUMEN

Bruton's tyrosine kinase (BTK) has emerged as a therapeutic target for B-cell malignancies, which is substantiated by the efficacy of various irreversible or reversible BTK inhibitors. However, on-target BTK mutations facilitating evasion from BTK inhibition lead to resistance that limits the therapeutic efficacy of BTK inhibitors. In this study we employed structure-based drug design strategies based on established BTK inhibitors and yielded a series of BTK targeting compounds. Among them, compound S-016 bearing a unique tricyclic structure exhibited potent BTK kinase inhibitory activity with an IC50 value of 0.5 nM, comparable to a commercially available BTK inhibitor ibrutinib (IC50 = 0.4 nM). S-016, as a novel irreversible BTK inhibitor, displayed superior kinase selectivity compared to ibrutinib and significant therapeutic effects against B-cell lymphoma both in vitro and in vivo. Furthermore, we generated BTK inhibitor-resistant lymphoma cells harboring BTK C481F or A428D to explore strategies for overcoming resistance. Co-culture of these DLBCL cells with M0 macrophages led to the polarization of M0 macrophages toward the M2 phenotype, a process known to support tumor progression. Intriguingly, we demonstrated that SYHA1813, a compound targeting both VEGFR and CSF1R, effectively reshaped the tumor microenvironment (TME) and significantly overcame the acquired resistance to BTK inhibitors in both BTK-mutated and wild-type BTK DLBCL models by inhibiting angiogenesis and modulating macrophage polarization. Overall, this study not only promotes the development of new BTK inhibitors but also offers innovative treatment strategies for B-cell lymphomas, including those with BTK mutations.

6.
Poult Sci ; 103(7): 103848, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38843610

RESUMEN

Pigeons infected with aviadenoviruses have been found worldwide. Recently, pigeon adenovirus 2 (PiAdV-2) has been widely distributed in racing pigeons in Germany. However, the epidemiology of this virus remains unclear due to the lack of a specific detection platform for PiAdV-2. In this study, we first detected PiAdV-2 positivity in racing pigeons (designated FJ21125 and FJ21128, which share 100% nucleotide identity with each other based on the fiber 2 gene) in Fujian, Southeast China. These genes shared 99.8% nucleotide identity with PiAdV-2 (GenBank No. NC_031501) but only 54.1% nucleotide identity with PiAdV-1 (GenBank No. NC024474). Then, the TaqMan-qPCR assay for the detection of PiAdV-2 was established based on fiber 2 gene characterization. The established assay had a correlation coefficient of 1.00, with an amplification efficiency of 99.0%. The minimum detection limit was 34.6 copies/µL. Only PiAdV-2 exhibited a positive fluorescent signal, and no signal was detected for other pathogens (including PiCV, FAdV-4, FAdV-8a, EDSV, PPMV-1, RVA and PiHV). The assay has good reproducibility, with a coefficient of variation less than 2.42% both intragroup and intergroup. The distributions of PiAdV-2 in fecal samples from YPDS (35 samples) and healthy (43 samples) racing pigeons from different geographical areas were investigated and were 37.14% (YPDS) and 20.93% (healthy), respectively. In summary, we developed a TaqMan-qPCR platform for the detection of PiAdV-2 infection with high sensitivity, specificity, and reproducibility. We confirmed the presence of PiAdV-2 in China, and our data suggested that there is no indication of a correlation between YPDS and PiAdV-2. This study provides more information on the pathogenesis mechanism and epidemiological surveillance of PiAdV-2.

7.
Heliyon ; 10(11): e31705, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38845982

RESUMEN

Acute myeloid leukemia (AML) is a prevalent hematological malignancy among adults. Recent studies suggest that the length of telomeres could significantly affect both the risk of developing AML and the overall survival (OS). Despite the limited focus on the prognostic value of telomere-related genes (TRGs) in AML, our study aims at addressing this gap by compiling a list of TRGs from TelNet, as well as collecting clinical information and TRGs expression data through the Gene Expression Omnibus (GEO) database. The GSE37642 dataset, sourced from GEO and based on the GPL96 platform, was divided into training and validation sets at a 6:4 ratio. Additionally, the GSE71014 dataset (based on the GPL10558 platform), GSE12417 dataset (based on the GPL96 and GPL570 platforms), and another portion of the GSE37642 dataset (based on the GPL570 platform) were designated as external testing sets. Univariate Cox regression analysis identified 96 TRGs significantly associated with OS. Subsequent Lasso-Cox stepwise regression analysis pinpointed eight TRGs (MCPH1, SLC25A6, STK19, PSAT1, KCTD15, DNMT3B, PSMD5, and TAF2) exhibiting robust predictive potential for patient survival. Both univariate and multivariate survival analyses unveiled TRG risk scores and age as independent prognostic variables. To refine the accuracy of survival prognosis, we developed both a nomogram integrating clinical parameters and a predictive risk score model based on TRGs. In subsequent investigations, associations were emphasized not solely regarding the TRG risk score and immune infiltration patterns but also concerning the response to immune-checkpoint inhibitor (ICI) therapy. In summary, the establishment of a telomere-associated genetic risk model offers a valuable tool for prognosticating AML outcomes, thereby facilitating informed treatment decisions.

8.
Front Vet Sci ; 11: 1374923, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38840641

RESUMEN

Introduction: Avian leukosis, a viral disease affecting birds such as chickens, presents significant challenges in poultry farming due to tumor formation, decreased egg production, and increased mortality. Despite the absence of a commercial vaccine, avian leukosis virus (ALV) infections have been extensively documented, resulting in substantial economic losses in the poultry industry. This study aimed to develop alginate-chitosan composite microspheres loaded with ALV-J Gp85 protein (referred to as aCHP-gp85) as a potential vaccine candidate. Methods: Sodium alginate and chitosan were utilized as encapsulating materials, with the ALV-J Gp85 protein serving as the active ingredient. The study involved 45 specific pathogen-free (SPF) chickens to evaluate the immunological effectiveness of aCHP-gp85 compared to a traditional Freund adjuvant-gp85 vaccine (Freund-gp85). Two rounds of vaccination were administered, and antibody levels, mRNA expression of immune markers, splenic lymphocyte proliferation, and immune response were assessed. An animal challenge experiment was conducted to evaluate the vaccine's efficacy in reducing ALV-J virus presence and improving clinical conditions. Results: The results demonstrated that aCHP-gp85 induced a significant and sustained increase in antibody levels compared to Freund-gp85, with the elevated response lasting for 84 days. Furthermore, aCHP-gp85 significantly upregulated mRNA expression levels of key immune markers, notably TNF-α and IFN-γ. The application of ALV-J Gp85 protein within the aCHP-gp85 group led to a significant increase in splenic lymphocyte proliferation and immune response. In the animal challenge experiment, aCHP-gp85 effectively reduced ALV-J virus presence and improved clinical conditions compared to other groups, with no significant pathological changes observed. Discussion: The findings suggest that aCHP-gp85 elicits a strong and prolonged immune response compared to Freund-gp85, indicating its potential as an innovative ALV-J vaccine candidate. These results provide valuable insights for addressing avian leukosis in the poultry industry, both academically and practically.

9.
iScience ; 27(6): 109979, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38832007

RESUMEN

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized by the Warburg effect, and the dynamic interplay between cancer cells and mitochondria. The role of cancer stem cells (CSCs) in treatment resistance and the regulatory influence of non-coding RNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are studied. The chapter emphasizes future directions, encompassing advancements in immunotherapy, strategies to counter adaptive resistance, integration of artificial intelligence for predictive modeling, and the identification of biomarkers for personalized treatment. The comprehensive exploration of these hallmarks provides a foundation for innovative therapeutic approaches, aiming to navigate the complex landscape of cancer resistance and enhance patient outcomes.

10.
Hortic Res ; 11(5): uhae066, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38725461

RESUMEN

CaWRKY40 coordinately activates pepper immunity against Ralstonia solanacearum infection (RSI) and high temperature stress (HTS), forms positive feedback loops with other positive regulators and is promoted by CaWRKY27b/CaWRKY28 through physical interactions; however, whether and how it is regulated by negative regulators to function appropriately remain unclear. Herein, we provide evidence that CaWRKY40 is repressed by a SALT TOLERANCE HOMOLOG2 in pepper (CaSTH2). Our data from gene silencing and transient overexpression in pepper and epoptic overexpression in Nicotiana benthamiana plants showed that CaSTH2 acted as negative regulator in immunity against RSI and thermotolerance. Our data from BiFC, CoIP, pull down, and MST indicate that CaSTH2 interacted with CaWRKY40, by which CaWRKY40 was prevented from activating immunity or thermotolerance-related genes. It was also found that CaSTH2 repressed CaWRKY40 at least partially through blocking interaction of CaWRKY40 with CaWRKY27b/CaWRKY28, but not through directly repressing binding of CaWRKY40 to its target genes. The results of study provide new insight into the mechanisms underlying the coordination of pepper immunity and thermotolerance.

11.
J Formos Med Assoc ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38729819

RESUMEN

BACKGROUND AND PURPOSE: Patients with hypervascular spinal tumors may have severe blood loss during tumor resection, which increases the risks of perioperative morbidity and mortality. However, the preoperative evaluation of tumor vascularity may be challenging; moreover, the reliability of the data obtained in conventional preoperative noninvasive imaging is debatable. In this study, we compared conventional magnetic resonance imaging (MRI) and subtraction computed tomography angiography (CTA) in terms of their performance in vascularity evaluation. The catheter digital subtraction angiography (DSA) technique was used as a reference standard. METHODS: This study included 123 consecutive patients with spinal tumor who underwent subtraction CTA, catheter DSA, and subsequent surgery between October 2015 and October 2021. Data regarding qualitative and semiquantitative subtraction CTA parameters and conventional MRI signs were collected for comparison with tumor vascularity graded through catheter DSA. The diagnostic performance of qualitative CTA, quantitative CTA, and conventional MRI in assessing spinal tumor vascularity was analyzed. RESULTS: Qualitative subtraction CTA was the best noninvasive imaging modality in terms of diagnostic performance (area under the receiver operating characteristic curve [AUROC], 0.95). Quantitative CTA was relatively inferior (AUROC, 0.87). MRI results had low reliability (AUROC, 0.51 to 0.59). Intratumoral hemorrhage and prominent foraminal venous plexus were found to be the specific signs for hypervascularity (specificity 93.2%). CONCLUSIONS: Qualitative subtraction CTA offers the highest diagnostic value in evaluating spinal tumor vascularity, compared to quantitative CTA and MRI. Although conventional MRI may not be a reliable approach, certain MRI signs may have high specificity, which may be crucial for assessing spinal tumor vascularity.

12.
Eur Radiol ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38724768

RESUMEN

OBJECTIVES: Developing a deep learning radiomics model from longitudinal breast ultrasound and sonographer's axillary ultrasound diagnosis for predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) in breast cancer. METHODS: Breast cancer patients undergoing NAC followed by surgery were recruited from three centers between November 2016 and December 2022. We collected ultrasound images for extracting tumor-derived radiomics and deep learning features, selecting quantitative features through various methods. Two machine learning models based on random forest were developed using pre-NAC and post-NAC features. A support vector machine integrated these data into a fusion model, evaluated via the area under the curve (AUC), decision curve analysis, and calibration curves. We compared the fusion model's performance against sonographer's diagnosis from pre-NAC and post-NAC axillary ultrasonography, referencing histological outcomes from sentinel lymph node biopsy or axillary lymph node dissection. RESULTS: In the validation cohort, the fusion model outperformed both pre-NAC (AUC: 0.899 vs. 0.786, p < 0.001) and post-NAC models (AUC: 0.899 vs. 0.853, p = 0.014), as well as the sonographer's diagnosis of ALN status on pre-NAC and post-NAC axillary ultrasonography (AUC: 0.899 vs. 0.719, p < 0.001). Decision curve analysis revealed patient benefits from the fusion model across threshold probabilities from 0.02 to 0.98. The model also enhanced sonographer's diagnostic ability, increasing accuracy from 71.9% to 79.2%. CONCLUSION: The deep learning radiomics model accurately predicted the ALN response to NAC in breast cancer. Furthermore, the model will assist sonographers to improve their diagnostic ability on ALN status before surgery. CLINICAL RELEVANCE STATEMENT: Our AI model based on pre- and post-neoadjuvant chemotherapy ultrasound can accurately predict axillary lymph node metastasis and assist sonographer's axillary diagnosis. KEY POINTS: Axillary lymph node metastasis status affects the choice of surgical treatment, and currently relies on subjective ultrasound. Our AI model outperformed sonographer's visual diagnosis on axillary ultrasound. Our deep learning radiomics model can improve sonographers' diagnosis and might assist in surgical decision-making.

13.
Innovations (Phila) ; : 15569845241248641, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38725287

RESUMEN

OBJECTIVE: In recent years, there has been an increasing focus on minimally invasive mediastinal surgery using a trans-subxiphoid single-port thoracoscopic approach. Despite its potential advantages, the widespread adoption of this method has been hindered by the intricate surgical maneuvers required within the confined retrosternal space. Robotic surgery offers the potential to overcome the limitations inherent in the thoracoscopic technique. METHODS: This was a clinical trial (NCT05455840) to evaluate the feasibility and safety of utilizing the da Vinci® SP system (Intuitive Surgical, Sunnyvale, CA, USA) for trans-subxiphoid single-port surgery in patients with anterior mediastinal disease. The primary endpoints encompassed conversion rates and the secondary endpoints included the occurrence of perioperative complications. RESULTS: Between August 2022 and April 2023, a total of 15 patients (7 men and 8 women; median age = 56 years, interquartile range [IQR]: 49 to 65 years) underwent trans-subxiphoid robotic surgery using da Vinci SP platform for maximal thymectomy (n = 2) or removal of anterior mediastinal masses (n = 13). All surgical procedures were carried out with success, with no need for conversion to open surgery or the creation of additional ports. The median docking time was 2 min (IQR: 1 to 4 min), while the console time had a median of 152 min (IQR: 95 to 191 min). There were no postoperative complications and patients experienced a median postoperative hospital stay of 2 days with no unplanned 30-day readmission. CONCLUSIONS: This study shows that trans-subxiphoid single-port robotic surgery employing the da Vinci SP system in patients with anterior mediastinal disease is clinically viable with acceptable safety and short-term outcomes.

15.
Int J Med Robot ; 20(3): e2634, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38767083

RESUMEN

BACKGROUND: Reducing the annotation burden is an active and meaningful area of artificial intelligence (AI) research. METHODS: Multiple datasets for the segmentation of two landmarks were constructed based on 41 257 labelled images and 6 different microsurgical scenarios. These datasets were trained using the multi-stage transfer learning (TL) methodology. RESULTS: The multi-stage TL enhanced segmentation performance over baseline (mIOU 0.6892 vs. 0.8869). Besides, Convolutional Neural Networks (CNNs) achieved a robust performance (mIOU 0.8917 vs. 0.8603) even when the training dataset size was reduced from 90% (30 078 images) to 10% (3342 images). When directly applying the weight from one certain surgical scenario to recognise the same target in images of other scenarios without training, CNNs still obtained an optimal mIOU of 0.6190 ± 0.0789. CONCLUSIONS: Model performance can be improved with TL in datasets with reduced size and increased complexity. It is feasible for data-based domain adaptation among different microsurgical fields.


Asunto(s)
Microcirugia , Redes Neurales de la Computación , Humanos , Microcirugia/métodos , Inteligencia Artificial , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos , Procedimientos Quirúrgicos Otorrinolaringológicos/métodos , Aprendizaje Automático , Cirugía Asistida por Computador/métodos , Puntos Anatómicos de Referencia
16.
J Inorg Biochem ; 257: 112615, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38772187

RESUMEN

A series of bis-naphthyl ferrocene derivatives were synthesized and characterized. Based on the results obtained from UV-visible absorption titration and ethidium bromide (EB) displacement experiments, it was observed that the synthesized compounds exhibited a strong binding ability to dsDNA. In comparison to the viscosity curve of EB, the tested compounds demonstrated a bisintercalation binding mode when interacting with CT-DNA. Differential pulse voltammetry (DPV) was employed to assess the binding specificity of these indicators towards ssDNA and dsDNA. All tested indicators displayed more pronounced signal differences before and after hybridization between probe nucleic acids and target nucleic acids compared to Methylene Blue (MB). Among the evaluated compounds, compound 3j containing an ether chain showed superior performance as an indicator, making it suitable for constructing DNA-based biosensors. Under optimized conditions including probe ssDNA concentration and indicator concentration, this biosensor exhibited good sensitivity, reproducibility, stability, and selectivity. The limit of detection was calculated as 4.53 × 10-11 mol/L. Furthermore, when utilizing 3j as the indicator in serum samples, the biosensor achieved satisfactory recovery rates for detecting the BRCA1 gene.

17.
Artículo en Inglés | MEDLINE | ID: mdl-38777778

RESUMEN

BACKGROUND: Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy caused by Aristolochic acid (AA). AAN is associated with the development of nephropathy and urothelial carcinoma. It is estimated that more than 100 million people worldwide are at risk of developing AAN. However, the underlying mechanisms driving renal deterioration in AAN remain poorly understood, and the treatment options are limited. METHODS: We obtained GSE27168 and GSE136276 series matrix data from the Gene Expression Omnibus (GEO) related to AAN. Using the R Studio environment, we applied the limma package and WGCNA package to identify co-differently expressed genes (co-DEGs). By GO/KEGG/GSVA analysis, we revealed common biological pathways. Subsequently, co-DEGs were subjected to the String database to construct a protein-protein interaction (PPI) network. The MCC algorithms implemented in the Cytohubba plugin were employed to identify hub genes. The hub genes were cross-referenced with the transcription factor (TF) database to identify hub TFs. Immune infiltration analysis was performed to identify key immune cell groups by utilizing CIBERSORT. The expressions of AAN-associated hub TFs were verified in vivo and in vitro. Finally, siRNA intervention was performed on the two TFs to verify their regulatory effect in AAN. RESULTS: Our analysis identified 88 co-DEGs through the "limma" and "WGCNA" R packages. A PPI network comprising 53 nodes and 34 edges was constructed with a confidence level >0.4. ATF3 and c-JUN were identified as hub TFs potentially linked to AAN. Additionally, expressions of ATF3 and c-JUN positively correlated with monocytes, basophils, and vessels, and negatively correlated with eosinophils and endothelial cells. We observed a significant increase in protein and mRNA levels of these two hub TFs. Furthermore, it was found that siRNA intervention targeting ATF3, but not c-JUN, alleviated cell damage induced by AA. The knockdown of ATF3 protects against oxidative stress and inflammation in the AAN cell model. CONCLUSION: This study provides novel insights into the role of ATF3 in AAN. The comprehensive analysis sheds light on the molecular mechanisms and identifies potential biomarkers and drug targets for AAN treatment.


Asunto(s)
Ácidos Aristolóquicos , Enfermedades Renales , Factores de Transcripción , Ácidos Aristolóquicos/toxicidad , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Enfermedades Renales/inducido químicamente , Enfermedades Renales/genética , Animales , Ratones , Humanos , Factor de Transcripción Activador 3/genética , Factor de Transcripción Activador 3/metabolismo , Mapas de Interacción de Proteínas
18.
Radiol Cardiothorac Imaging ; 6(3): e230278, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38780426

RESUMEN

Purpose To develop a prediction model combining both clinical and CT texture analysis radiomics features for predicting pneumothorax complications in patients undergoing CT-guided core needle biopsy. Materials and Methods A total of 424 patients (mean age, 65.6 years ± 12.7 [SD]; 232 male, 192 female) who underwent CT-guided core needle biopsy between January 2021 and October 2022 were retrospectively included as the training data set. Clinical and procedure-related characteristics were documented. Texture analysis radiomics features were extracted from the subpleural lung parenchyma traversed by needle. Moderate pneumothorax was defined as a postprocedure air rim of 2 cm or greater. The prediction model was developed using logistic regression with backward elimination, presented by linear fusion of the selected features weighted by their coefficients. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). Validation was conducted in an external cohort (n = 45; mean age, 58.2 years ± 12.7; 19 male, 26 female) from a different hospital. Results Moderate pneumothorax occurred in 12.0% (51 of 424) of the training cohort and 8.9% (four of 45) of the external test cohort. Patients with emphysema (P < .001) or a longer needle path length (P = .01) exhibited a higher incidence of moderate pneumothorax in the training cohort. Texture analysis features, including gray-level co-occurrence matrix cluster shade (P < .001), gray-level run-length matrix low gray-level run emphasis (P = .049), gray-level run-length matrix run entropy (P = .003), gray-level size-zone matrix gray-level variance (P < .001), and neighboring gray-tone difference matrix complexity (P < .001), showed higher values in patients with moderate pneumothorax. The combined clinical-radiomics model demonstrated satisfactory performance in both the training (AUC 0.78, accuracy = 71.9%) and external test cohorts (AUC 0.86, accuracy 73.3%). Conclusion The model integrating both clinical and radiomics features offered practical diagnostic performance and accuracy for predicting moderate pneumothorax in patients undergoing CT-guided core needle biopsy. Keywords: Biopsy/Needle Aspiration, Thorax, CT, Pneumothorax, Core Needle Biopsy, Texture Analysis, Radiomics, CT Supplemental material is available for this article. © RSNA, 2024.


Asunto(s)
Biopsia Guiada por Imagen , Neumotórax , Tomografía Computarizada por Rayos X , Humanos , Neumotórax/etiología , Neumotórax/epidemiología , Neumotórax/diagnóstico por imagen , Masculino , Femenino , Anciano , Biopsia Guiada por Imagen/métodos , Biopsia Guiada por Imagen/efectos adversos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Biopsia con Aguja Gruesa/métodos , Biopsia con Aguja Gruesa/efectos adversos , Persona de Mediana Edad , Radiografía Intervencional/métodos , Pulmón/patología , Pulmón/diagnóstico por imagen , Valor Predictivo de las Pruebas , Radiómica
19.
Curr Issues Mol Biol ; 46(5): 4688-4700, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38785551

RESUMEN

Subarachnoid hemorrhage (SAH) is a type of stroke caused by bleeding into the subarachnoid space. SAH is a medical emergency and requires prompt treatment to prevent complications such as seizures, stroke, or other brain damage. Treatment options may include surgery, medication, or a combination of both. 2-Cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), a compound with anti-inflammatory and antioxidant properties, is currently being investigated as a potential treatment for various diseases, including chronic kidney disease and pulmonary arterial hypertension. In this study, the effects of CDDO on rats subjected to SAH were evaluated. Male Sprague-Dawley rats were divided into four groups (n = 6/group): (1) control group, (2) SAH group, (3) SAH + low-dose CDDO (10 mg/kg injected into the subarachnoid space at 24 h after SAH) group, and (4) SAH + high-dose CDDO (20 mg/kg) group. CDDO improved SAH-induced poor neurological outcomes and reduced vasospasm in the basal artery following SAH. It also decreased the SAH-induced expression of proinflammatory cytokines such as TNF-α, IL-1ß, and IL-6 in both the cerebrospinal fluid and serum samples as determined by ELISA. A Western blot analysis confirmed an increase in the p-NF-κB protein level after SAH, but it was significantly decreased with CDDO intervention. Immunofluorescence staining highlighted the proliferation of microglia and astrocytes as well as apoptosis of the neuronal cells after SAH, and treatment with CDDO markedly reduced the proliferation of these glial cells and apoptosis of the neuronal cells. The early administration of CDDO after SAH may effectively mitigate neuronal apoptosis and vasospasm by suppressing inflammation.

20.
Hu Li Za Zhi ; 71(3): 75-84, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-38817139

RESUMEN

BACKGROUND: Critically ill neonates receive care in the neonatal intensive care unit (NICU). Unfortunately, some neonates pass away in the NICU. Providing comprehensive neonatal palliative care and hospice services is crucial in supporting parents through the loss of their offspring. In our NICU, we identified that only 74.5% of nurses are able to properly recognize the need for palliative care and only 55% are able to implement the necessary procedures. PURPOSE: A project was designed and implemented to enhance the ability of nursing staff to recognize the need for and properly implement palliative care to improve the quality of this care in the NICU. RESOLUTIONS: We organized an on-the-job education and training program within our NICU with the goals of heightening awareness among nursing staff. In addition, a specialist palliative care operation flow chart, process preparation checklist, and palliative-care-related tools were created to facilitate the care process. RESULTS: After program implementation, among nursing staff in our NICU, the palliative care recognition accuracy rate rose to 100% (from 74.5%) and the implementation rate rose to 94.8% (from 55%). The quality of provided neonatal palliative care and hospice services was significantly improved. CONCLUSIONS: The developed program was shown to significantly improve nursing staff recognition and implementation of neonatal palliative care in our NICU. This experience provides a reference for improving palliative care quality and for helping families effectively manage end-of-life challenges.


Asunto(s)
Unidades de Cuidado Intensivo Neonatal , Cuidados Paliativos , Humanos , Recién Nacido
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA