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1.
Insights Imaging ; 15(1): 230, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39311997

RESUMO

OBJECTIVES: To establish superb microvascular imaging (SMI) based thyroid imaging reporting and data system (SMI TI-RADS) for risk stratification of malignancy in thyroid nodules. METHODS: In total, 471 patients, comprising 643 thyroid nodules, who received conventional ultrasound (US), SMI, and a final diagnosis were extensively analyzed. A qualitative assessment of US features of the nodules was performed followed by univariable and multivariable logistic regression analyses, leading to the construction of the SMI TI-RADS, which was further verified using internal and external validation cohorts. RESULTS: Among the stand-alone US, predictive factors were the shape and margins of the nodules, echogenicity and echogenic foci, vascularity, extrathyroidal extension, ring-SMI patterns, penetrating vascularity, flow-signal enlarged, and vascularity area ratio. SMI TI-RADS depicted an enhanced area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI: 0.92, 0.96; p < 0.001 relative to other stratification systems), a 79% biopsy yield of malignancy (BYM, 189/240 nodules), and a 21% unnecessary biopsy rate (UBR, 51/240 nodules). In the verification cohorts, we demonstrated AUCs, malignancy biopsy yields, and unnecessary biopsy rates of 0.88 (95% CI: 0.83, 0.94), 79% (59/75 nodules), and 21% (16/75 nodules) for the internal cohort, respectively, and 0.91 (95% CI: 0.85, 0.96), 72% (31/43 nodules), and 28% (12/43 nodules) for the external cohort, respectively. CONCLUSION: SMI TI-RADS was found to be superior in diagnostic sensitivity, specificity, and efficiency than existing TI-RADSs, showing better stratification of the malignancy risk, and thus decreasing the rate of unnecessary needle biopsy. CRITICAL RELEVANCE STATEMENT: To develop an imaging and data system based on conventional US and SMI features for stratifying the malignancy risk in thyroid nodules. KEY POINTS: SMI features could improve thyroid nodule risk stratification. SMI TI-RADS showed superior diagnostic efficiency and accuracy for biopsy guidance. SMI TI-RADS can provide better guidance for clinical diagnosis and treatment of thyroid nodules.

2.
J Virol ; : e0132224, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39254313

RESUMO

The phosphatidyl-inositol 3-kinase/serine-threonine kinase (PI3K/ AKT) signaling pathway constitutes a classical phosphorylation cascade that integrates tyrosine, lipid, and serine acid-threonine phosphorylation, affecting cell function. The pathway is vulnerable to viral infection. Newcastle disease virus (NDV) poses a significant threat to the global poultry industry; however, its mechanism of early viral cell invasion and pathogenesis remain unclear. Previous in vivo and in vitro studies have shown that NDV infection activates PI3K/AKT signaling; however, it remains unclear whether NDV establishes infection through endocytosis regulated by this pathway. This study aimed to examine whether different genotypes of NDV strains could activate the PI3K/AKT signaling pathway within 2 h of in vitro infection. This activation, which relies on PI3K phosphorylation, remains unaffected by the phosphorylation-phosphatase and tensin homolog/phosphatase and tensin homolog (p-PTEN/PTEN) signaling pathway. Moreover, inhibition of PI3K activity impedes NDV replication. Additionally, interfering with the PI3K regulatory subunit p85 has no significant effect on NDV replication. Conversely, the tyrosine kinase activity upstream of PI3K can influence AKT activation and viral replication, particularly through vascular endothelial growth factor receptor 2 (VEGFR2). Additionally, NDV F protein primarily mediates PI3K and AKT phosphorylation to activate the PI3K/AKT signaling pathway. NDV F and VEGFR2 proteins, along with the PI3K p85α subunit, interact and co-localize at the cell membrane. NDV-induced PI3K/AKT signaling pathway activation impacts clathrin-mediated endocytosis, with VEGFR2 playing a pivotal role. In conclusion, this study shows that NDV infection is established early through F protein binding to VEGFR2, activating the PI3K/AKT signaling pathway and inducing clathrin-mediated endocytosis, supporting infection prevention and control measures. IMPORTANCE: Newcastle disease virus (NDV) is a threat to the global poultry industry; however, the mechanisms of NDV infection remain unclear. NDV affects the phosphatidyl-inositol 3-kinase/serine-threonine kinase (PI3K/ AKT) signaling pathway, requiring endocytosis for successful infection. Based on previous studies, we identified a close correlation between NDV infection and replication and the PI3K/AKT signaling pathway activity. This study examined the molecular mechanisms through which NDV activates the PI3K/AKT signaling pathway to regulate endocytosis and facilitate infection. This study showed that early-stage in vitro NDV infection activated the PI3K/AKT signaling pathway, enhancing clathrin-mediated endocytosis, crucial for infection onset. Notably, this process involves the interaction between NDV F protein and the vascular endothelial growth factor receptor 2 tyrosine kinase, leading to the subsequent binding and phosphorylation of the PI3K p85α regulatory subunit. This activation primes PI3K, initiating a cascade that promotes clathrin-mediated endocytosis. Our findings elucidate how NDV capitalizes on the PI3K/AKT signaling pathway to establish infection through endocytosis.

3.
J Cell Mol Med ; 28(16): e70013, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39199011

RESUMO

Crohn's disease (CD) presents with diverse clinical phenotypes due to persistent inflammation of the gastrointestinal tract. Its global incidence is on the rise. Neutrophil extracellular traps (NETs) are networks released by neutrophils that capture microbicidal proteins and oxidases targeting pathogens. Research has shown that NETs are implicated in the pathogenesis of several immune-mediated diseases such as rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease. The goal of this study was to identify a panel of NET-related genes to construct a diagnostic and therapeutic model for CD. Through analysis of the GEO database, we identified 1950 differentially expressed genes (DEGs) associated with CD. Gene enrichment and immune cell infiltration analyses indicate that neutrophil infiltrates and chemokine-related pathways are predominantly involved in CD, with other immune cells such as CD4 and M1 macrophages also playing a role in disease progression. Utilizing weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) networks, we identified six hub genes (SPP1, SOCS3, TIMP1, IRF1, CXCL2 and CD274). To validate the accuracy of our model, we performed external validation with statistical differences(p < 0.05). Additionally, immunohistochemical experiments demonstrated higher protein expression of the hub genes in colonic tissues from CD patients compared to healthy subjects (p < 0.05). In summary, we identified six effective hub genes associated with NETs as potential diagnostic markers for CD. These markers not only offer targets for future research but also hold promise for the development of novel therapeutic interventions for CD.


Assuntos
Biologia Computacional , Doença de Crohn , Armadilhas Extracelulares , Redes Reguladoras de Genes , Mapas de Interação de Proteínas , Humanos , Doença de Crohn/genética , Doença de Crohn/imunologia , Doença de Crohn/patologia , Biologia Computacional/métodos , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/genética , Mapas de Interação de Proteínas/genética , Perfilação da Expressão Gênica , Neutrófilos/metabolismo , Neutrófilos/imunologia , Regulação da Expressão Gênica , Biomarcadores , Bases de Dados Genéticas
4.
Brain Res Bull ; 217: 111057, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39209069

RESUMO

Epilepsy with recurrent seizures is characterized by neuronal damage and glial proliferation induced by brain inflammation. Recurrent seizures can lead to changes in the microRNA (miRNA) spectrum, significantly influencing the inflammatory response of microglia. MiR-155-5p, as a pro-inflammatory miRNA, is increased in the epileptic brain. However, its specific role in acute seizures remains unknown. The study aimed to develop a new strategy for treating epilepsy by investigating how silencing of miR-155-5p initiated its anticonvulsive mechanism. The level of miR-155-5p was up-regulated in the hippocampus of epileptic immature rats induced by kainic acid (KA). The use of antago-miR-155-5p exerted significant beneficial effects on the seizure scores, brain discharges and cognition in immature rats following KA-induced epilepsy. Antago-miR-155-5p also inhibited neuron damage and microglial activation. Moreover, the silencing of miR-155-5p significantly inhibited the Dual-specificity phosphatase 14 (Dusp14)/ mitogen-activated protein kinase (MAPK) axis in vivo. MiR-155-5p interacted with dusp14 to regulate MAPK signaling way expression, verified by a dual-luciferase reporter assay. The results suggested that the silencing of miR-155-5p might reduce hippocampal damage in epileptic immature rats induced by KA via Dusp14/MAPK signaling way. This implied that miR-155-5p could serve as a therapeutic tool to prevent the development of epilepsy.

5.
Eur J Med Res ; 29(1): 366, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014466

RESUMO

PURPOSE: Our study aimed to develop and validate a homologous recombination deficiency (HRD) scoring algorithm in the Chinese breast cancer population. METHODS AND MATERIALS: Ninety-six in-house breast cancer (BC) samples and 6 HRD-positive standard cells were analyzed by whole-genome sequencing (WGS). Besides, 122 BCs from the TCGA database were down-sampled to ~ 1X WGS. We constructed an algorithm named AcornHRD for HRD score calculated based on WGS at low coverage as input data to estimate large-scale copy number alteration (LCNA) events on the genome. A clinical cohort of 50 BCs (15 cases carrying BRCA mutation) was used to assess the association between HRD status and anthracyclines-based neoadjuvant treatment outcomes. RESULTS: A 100-kb window was defined as the optimal size using 41 in-house cases and the TCGA dataset. HRD score high threshold was determined as HRD score ≥ 10 using 55 in-house BCs with BRCA mutation to achieve a 95% BRCA-positive agreement rate. Furthermore, the HRD status agreement rate of AcornHRD is 100%, while the ShallowHRD is 60% in standard cells. BRCA mutation was significantly associated with a high HRD score evaluated by AcornHRD and ShallowHRD (p = 0.008 and p = 0.003, respectively) in the TCGA dataset. However, AcornHRD showed a higher positive agreement rate than did the ShallowHRD algorithm (70% vs 60%). In addition, the BRCA-positive agreement rate of AcornHRD was superior to that of ShallowHRD (87% vs 13%) in the clinical cohort. Importantly, the high HRD score assessed by AcornHRD was significantly correlated with a residual cancer burden score of 0 or 1 (RCB0/1). Besides, the HRD-positive group was more likely to respond to anthracycline-based chemotherapy than the HRD-negative group (pCR [OR = 9.5, 95% CI 1.11-81.5, p = 0.040] and RCB0/1 [OR = 10.29, 95% CI 2.02-52.36, p = 0.005]). CONCLUSION: Using the AcornHRD algorithm evaluation, our analysis demonstrated the high performance of the LCNA genomic signature for HRD detection in breast cancers.


Assuntos
Algoritmos , Antraciclinas , Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Feminino , Antraciclinas/uso terapêutico , Antraciclinas/administração & dosagem , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , China/epidemiologia , Adulto , Recombinação Homóloga , Mutação , Idoso , Variações do Número de Cópias de DNA , Proteína BRCA1/genética
7.
Front Oncol ; 14: 1388575, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38764572

RESUMO

Background: Multiple primary lung cancer (MPLC) is an increasingly well-known clinical phenomenon. However, its molecular characterizations are poorly understood, and still lacks of effective method to distinguish it from intrapulmonary metastasis (IM). Herein, we propose an identification model based on molecular multidimensional analysis in order to accurately optimize treatment. Methods: A total of 112 Chinese lung cancers harboring at least two tumors (n = 270) were enrolled. We retrospectively selected 74 patients with 121 tumor pairs and randomly divided the tumor pairs into a training cohort and a test cohort in a 7:3 ratio. A novel model was established in training cohort, optimized for MPLC identification using comprehensive genomic profiling analyzed by a broad panel with 808 cancer-related genes, and evaluated in the test cohort and a prospective validation cohort of 38 patients with 112 tumors. Results: We found differences in molecular characterizations between the two diseases and rigorously selected the characterizations to build an identification model. We evaluated the performance of the classifier using the test cohort data and observed an 89.5% percent agreement (PA) for MPLC and a 100.0% percent agreement for IM. The model showed an excellent area under the curve (AUC) of 0.947 and a 91.3% overall accuracy. Similarly, the assay achieved a considerable performance in the independent validation set with an AUC of 0.938 and an MPLC predictive value of 100%. More importantly, the MPLC predictive value of the classification achieved 100% in both the test set and validation cohort. Compared to our previous mutation-based method, the classifier showed better κ consistencies with clinical classification among all 112 patients (0.84 vs. 0.65, p <.01). Conclusion: These data provide novel evidence of MPLC-specific genomic characteristics and demonstrate that our one-step molecular classifier can accurately classify multifocal lung tumors as MPLC or IM, which suggested that broad panel NGS may be a useful tool for assisting with differential diagnoses.

8.
J Cancer ; 15(11): 3452-3465, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38817853

RESUMO

Background: S100A8/S100A9 belong to the S100 calcium-binding protein family and play an essential role in the progression of chronic inflammation in diseases. It also regulates various biological processes such as tumor cell survival, apoptosis, and invasive metastasis. The extracellular form of S100A8/S100A9 functions by modulating cellular oxidative metabolism and facilitating inflammation-to-cancer progression. This modulation occurs through specific binding to receptors like RAGE and TLR4 and activation of signaling pathways including STAT3 and NF-κB. In tumor cells, S100A8 and S100A9 induce phenotypic changes by influencing calcium ion concentrations and other pathways. However, the precise function of high S100A8/S100A9 expression in colorectal cancer cells remains unclear. Methods: To explore the role of S100A8/S100A9 in colorectal cancer, we used immunohistochemistry and data from GEO and TCGA databases to analyze its expression in colorectal cancer cells, normal intestinal mucosa, and adjacent tissues. Functional models of high S100A8/S100A9 expression in colorectal cancer cells were established through transfection with overexpression plasmids. Protein microarrays, enzyme-linked immunosorbent assays (ELISAs), and real-time PCR were employed to assess the expression and secretion of 40 cytokines. MTT and Transwell invasion assays were conducted to evaluate changes in cell proliferation, invasion, and chemotaxis. Finally, tail vein and subcutaneous tumorigenesis assays assessed cell proliferation and migration in vivo. Results: We observed significantly higher expression of S100A8/S100A9 in colorectal cancer epithelial cells compared to normal intestinal mucosa and adjacent tissues. Overexpression of S100A8/S100A9 in mouse colon cancer cells CT26.WT led to differential increases in the secretion levels of various cytokines (CXCL5, CXCL11, GM-CSF, G-CSF, IL1a, IL1b, sTNF RI, and CCL3). Additionally, this overexpression activated signaling pathways such as STAT3, NF-κB, and ERK-MAPK. The synthesis and secretion of inflammatory factors could be inhibited by using NF-κB and ERK-MAPK pathway inhibitors. Moreover, S100A8 promotes the proliferation and invasion of colon cancer cells. Notably, the CXCR2 inhibitor (SB265610) effectively reversed the phenotypic changes induced by the CXCL5/CXCR2 biological axis. Conclusions: Our findings indicate that increased expression of S100A8 and S100A9 in colon cancer epithelial cells enhances the secretion of inflammatory factors by activating NF-κB, ERK-MAPK, and other signaling pathways. S100A8 facilitates colon cancer cell proliferation, invasion, and metastasis through the CXCL5/CXCR2 biological axis.

9.
Cancer Lett ; 596: 216977, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38795759

RESUMO

Adenosis is a benign breast condition whose lesions can mimic breast carcinoma and is evaluated for malignancy with the Breast Imaging-Reporting and Data System (BI-RADS). We construct and validate the performance of modality-specific enhancement (MSE)-Breast Net based on multimodal ultrasound images and compare it to the BI-RADS in differentiating adenosis from breast cancer. A total of 179 patients with breast carcinoma and 229 patients with adenosis were included in this retrospective, two-institution study, then divided into a training cohort (institution I, n = 292) and a validation cohort (institution II, n = 116). In the training cohort, the final model had a significantly greater AUC (0.82; P < 0.05) than B-mode-based model (0.69, 95% CI [0.49-0.90]). In the validation cohort, the AUC of the final model was 0.81, greater than that of the BI-RADS (0.75, P < 0.05). The multimodal model outperformed the individual and bimodal models, reaching a significantly greater AUC of 0.87 (95% CI = 0.69-1.0) (P < 0.05). MSE-Breast Net, based on multimodal ultrasound images, exhibited better diagnostic performance than the BI-RADS in differentiating adenosis from breast cancer and may contribute to clinical diagnosis and treatment.


Assuntos
Neoplasias da Mama , Ultrassonografia Mamária , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Ultrassonografia Mamária/métodos , Adulto , Idoso , Diagnóstico Diferencial , Doença da Mama Fibrocística/diagnóstico por imagem , Doença da Mama Fibrocística/patologia
10.
Int J Biol Macromol ; 271(Pt 2): 132529, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38777010

RESUMO

The poor UV shielding property of PLA limit it further applications on food packaging. The rare-earth complex Eu(DBM)3phen converts absorbed ultraviolet (UV) light to red light, which inspires the development of new UV shielding materials. However, this complex has low photostability and decomposes easily under UV irradiation. Thus, we prepared a long-lasting rare-earth complex transluminant Eu(DBM)2(BP-2)phen by introducing BP-2 into Eu(DBM)3phen, and blended it with PLA to obtain PLA/Eu(DBM)2(BP-2)phen composite films. The test results showed that the complex could reduce the UV transmittance of PLA films by emitting luminescence and heat. The UV transmittance of the composite film with 0.5 % mass fraction decreased from 87.4 % to 7.7 %, compared to pure PLA films, and remained at 11.6 % after 12 days of UV aging. The film had long-lasting UV shielding performance, good transparency and mechanical properties. Finally, In the storage experiments of flaxseed oil, the P/E25 film effectively retarded the oxidation process of the oil.


Assuntos
Európio , Embalagem de Alimentos , Poliésteres , Raios Ultravioleta , Poliésteres/química , Európio/química , Embalagem de Alimentos/métodos , Óleo de Semente do Linho/química
12.
Mol Cancer ; 23(1): 57, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504268

RESUMO

Urine-based testing is promising for noninvasive diagnosis of urothelial carcinoma (UC) but has suboptimal sensitivity for early-stage tumors. Herein, we developed a multitarget urine tumor DNA test, UI-Seek, for UC detection and evaluated its clinical feasibility. The prediction model was developed in a retrospective cohort (n = 382), integrating assays for FGFR3 and TERT mutations and aberrant ONECUT2 and VIM methylation to generate a UC-score. The test performance was validated in a double-blinded, multicenter, prospective trial (n = 947; ChiCTR2300076543) and demonstrated a sensitivity of 91.37% and a specificity of 95.09%. The sensitivity reached 75.81% for low-grade Ta tumors and exceeded 93% in high-grade Ta and higher stages (T1 to T4). Simultaneous identification of both bladder and upper urinary tract tumors was enabled with sensitivities exceeding 90%. No significant confounding effects were observed regarding benign urological diseases or non-UC malignancies. The test showed improved sensitivities over urine cytology, the NMP22 test, and UroVysion FISH alongside comparable specificities. The single-target accuracy was greater than 98% as confirmed by Sanger sequencing. Post-surgery UC-score decreased in 97.7% of subjects. Overall, UI-Seek demonstrated robust performance and considerable potential for the early detection of UC.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/urina , Estudos Retrospectivos , Estudos Prospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , DNA , Biomarcadores Tumorais/genética , Fatores de Transcrição , Proteínas de Homeodomínio
13.
Endoscopy ; 56(5): 334-342, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38412993

RESUMO

BACKGROUND: Inaccurate Forrest classification may significantly affect clinical outcomes, especially in high risk patients. Therefore, this study aimed to develop a real-time deep convolutional neural network (DCNN) system to assess the Forrest classification of peptic ulcer bleeding (PUB). METHODS: A training dataset (3868 endoscopic images) and an internal validation dataset (834 images) were retrospectively collected from the 900th Hospital, Fuzhou, China. In addition, 521 images collected from four other hospitals were used for external validation. Finally, 46 endoscopic videos were prospectively collected to assess the real-time diagnostic performance of the DCNN system, whose diagnostic performance was also prospectively compared with that of three senior and three junior endoscopists. RESULTS: The DCNN system had a satisfactory diagnostic performance in the assessment of Forrest classification, with an accuracy of 91.2% (95%CI 89.5%-92.6%) and a macro-average area under the receiver operating characteristic curve of 0.80 in the validation dataset. Moreover, the DCNN system could judge suspicious regions automatically using Forrest classification in real-time videos, with an accuracy of 92.0% (95%CI 80.8%-97.8%). The DCNN system showed more accurate and stable diagnostic performance than endoscopists in the prospective clinical comparison test. This system helped to slightly improve the diagnostic performance of senior endoscopists and considerably enhance that of junior endoscopists. CONCLUSION: The DCNN system for the assessment of the Forrest classification of PUB showed satisfactory diagnostic performance, which was slightly superior to that of senior endoscopists. It could therefore effectively assist junior endoscopists in making such diagnoses during gastroscopy.


Assuntos
Úlcera Péptica Hemorrágica , Humanos , Úlcera Péptica Hemorrágica/diagnóstico , Úlcera Péptica Hemorrágica/classificação , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Feminino , Inteligência Artificial , Redes Neurais de Computação , Curva ROC , Estudos Prospectivos , Idoso , Gravação em Vídeo , Gastroscopia/métodos , Reprodutibilidade dos Testes , Adulto
14.
Int J Mol Sci ; 25(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38338959

RESUMO

Hydropericardium hepatitis syndrome (HHS) is primarily caused by fowl adenovirus serotype 4 (FAdV-4), causing high mortality in chickens. Although vaccination strategies against FAdV-4 have been adopted, HHS still occurs sporadically. Furthermore, no effective drugs are available for controlling FAdV-4 infection. However, type I and III interferon (IFN) are crucial therapeutic agents against viral infection. The following experiments were conducted to investigate the inhibitory effect of chicken IFN against FadV-4. We expressed recombinant chicken type I IFN-α (ChIFN-α) and type III IFN-λ (ChIFN-λ) in Escherichia coli and systemically investigated their antiviral activity against FAdV-4 infection in Leghorn male hepatocellular (LMH) cells. ChIFN-α and ChIFN-λ dose dependently inhibited FAdV-4 replication in LMH cells. Compared with ChIFN-λ, ChIFN-α more significantly inhibited viral genome transcription but less significantly suppressed FAdV-4 release. ChIFN-α- and ChIFN-λ-induced IFN-stimulated gene (ISG) expression, such as PKR, ZAP, IRF7, MX1, Viperin, IFIT5, OASL, and IFI6, in LMH cells; however, ChIFN-α induced a stronger expression level than ChIFN-λ. Thus, our data revealed that ChIFN-α and ChIFN-λ might trigger different ISG expression levels, inhibiting FAdV-4 replication via different steps of the FAdV-4 lifecycle, which furthers the potential applications of IFN antiviral drugs in chickens.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Doenças das Aves Domésticas , Animais , Masculino , Galinhas , Interferon-alfa/farmacologia , Interferon-alfa/genética , Sorogrupo , Adenoviridae/genética , Antivirais/farmacologia , Doenças das Aves Domésticas/tratamento farmacológico
15.
Vet Microbiol ; 289: 109949, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38128444

RESUMO

Newcastle disease (ND) is a highly pathogenic, contagious, and fatal infectious disease in poultry caused by the Newcastle disease virus (NDV). The PI3K/AKT signaling pathway is a phosphorylation cascade that participates in regulating several cellular functions. Viruses reportedly regulate the course of infection through the PI3K/AKT axis. Here, we aimed to analyze the pathogenesis of NDV infection mediated by the PI3K/AKT signaling pathway activation. We found that NDV infection can phosphorylate AKT to activate the PI3K/AKT axis both in vitro and in vivo. Flow cytometry and Caspase-3 activity assay showed that NDV infection could inhibit cell apoptosis. The activation or inhibition of the PI3K/AKT signaling pathway activity significantly inhibited or promoted NDV-mediated apoptosis. Furthermore, inhibition of cell apoptosis significantly promoted NDV replication. Overall, our results showed that NDV infection activates the PI3K/AKT signaling pathway and inhibits cell apoptosis, thus promoting viral replication. In this context, the reduced expression of PHLPP2 protein mediated by NDV infection could be inhibited by MG132. PHLPP2 expression reversely and positively regulated NDV replication and cell apoptosis, respectively. These results indicated that NDV infection-mediated activation of the PI3K/AKT signaling pathway and the inhibition of apoptosis depend on the ubiquitin-proteasome degradation of the PHLPP2 protein. Co-IP and indirect immunofluorescence results showed that NDV V protein could interact with PHLPP2 protein, indicating that NDV targeted PHLPP2 protein degradation through V protein to activate the PI3K/AKT signaling pathway. This study deepens our understanding of the molecular mechanisms of NDV infection, providing a theoretical basis for ND prevention and control.


Assuntos
Doença de Newcastle , Vírus da Doença de Newcastle , Animais , Vírus da Doença de Newcastle/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Apoptose , Replicação Viral
16.
ACS Appl Bio Mater ; 7(1): 104-113, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-38149377

RESUMO

The pursuit of environmentally friendly and highly effective antifouling materials for marine applications is of paramount importance. In this study, we successfully synthesized novel rare earth-based complexes by coordinating cerium (Ce III), samarium (Sm III), and europium (Eu III) with pyrithione (1-hydroxy-2-pyridinethione; PT). Extensive characterizations were performed, including single-crystal X-ray analysis, which revealed the intriguing binuclear structure of these complexes. This structural motif comprises two rare-earth ions intricately double-bridged by two oxygen atoms from the PT ligand, resulting in a distinctive and intriguing geometry. Furthermore, the central rare earth ion is surrounded by three sulfur atoms and two additional oxygen atoms, forming a unique distorted bicapped trigonal prismatic configuration. Compared with conventional antifouling biocides such as sodium pyrithione (NaPT), copper pyrithione (CuPT), and zinc pyrithione (ZnPT), these newly synthesized rare-earth complexes exhibited a remarkable boost in their in vitro antibacterial efficacy against both Gram-positive and Gram-negative bacteria. Additionally, these complexes demonstrated significant potential as antialgal agents, displaying impressive activity against marine planktonic organisms. These findings underscore the promising application prospects of these rare-earth complexes in the field of marine antifouling.


Assuntos
Antibacterianos , Bactérias Gram-Negativas , Piridinas , Tionas , Antibacterianos/farmacologia , Bactérias Gram-Positivas , Oxigênio
17.
J Mater Chem B ; 11(47): 11222-11227, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-38013489

RESUMO

The development of new cryoprotectants for cryopreservation of cells has attracted considerable interest. Herein, five calixarene-based CPAs (SC4A, S-S-C4A, S-SO2-C4A, SBAC4A, and CAC4A) were developed, and their IRI activity, DIS property and cryoprotective effect were studied. SBAC4A with a sulphobetaine zwitterion and SC4A with sulfo group modification possessed better cryoprotective effects than the other calixarene-based CPAs, especially for SBAC4A with the enhanced cell viabilities of 16.16 ± 1.78%, 12.60 ± 1.15% and 14.90 ± 1.66% against MCF-7, hucMSCs and A549 cells, respectively. This result provides a supramolecular principle for developing novel CPAs with consideration of the factors of hydrogen bonding, the macromolecular crowding principle and the three-dimensional (3D) structure.


Assuntos
Calixarenos , Crioprotetores , Crioprotetores/farmacologia , Crioprotetores/química , Gelo , Calixarenos/farmacologia , Criopreservação/métodos , Sobrevivência Celular
18.
Medicine (Baltimore) ; 102(41): e34513, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37832134

RESUMO

Overweight and obesity among adolescents has become a common public health problem, and both obesity rates and the amount of pocket money among adolescents in China are rising. We investigated to what extent the increase in pocket money could lead to weight gain of junior high school students and how this association may vary by school environment in China. Researchers utilized 3 waves of data from the China Education Panel Survey, a national longitudinal study, to investigate the likelihood of overweight and obesity. The Generalized Estimation Equation was employed to analyze the data. Three Generalized Estimation Equation models were constructed to explore the relationship between pocket money and overweight and obesity in 2 distinct food environments surrounding schools. A total of 8903 individuals (4604 boys and 4299 girls) from the China Education Panel Survey were analyzed. After adjusting for confounding factors, it was found that girls who received 20 to 49 yuan and ≥ 50 yuan per week had a higher risk of overweight and obesity compared to those who received 0 to 9 yuan per week (OR = 1.34, 95% CI: 1.07-1.69, OR = 1.53, 95% CI: 1.22-1.92). However, no significant association was observed between pocket money and overweight and obesity when food around the school was not easily accessible. The prevalence of overweight among Chinese teenagers has steadily increased from Wave1 to Wave3. Moreover, junior high school girls who receive more pocket money are at a greater risk of developing obesity and overweight issues.


Assuntos
Obesidade , Sobrepeso , Masculino , Feminino , Adolescente , Humanos , Sobrepeso/epidemiologia , Estudos Longitudinais , Obesidade/epidemiologia , Instituições Acadêmicas , Estudantes , China/epidemiologia , Prevalência , Índice de Massa Corporal
19.
Front Vet Sci ; 10: 1181916, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841466

RESUMO

Introduction: Newcastle disease virus (NDV) is prevalent worldwide with an extensive host range. Among birds infected with velogenic NDV strains, chickens experience high pathogenicity and mortality, whereas ducks mostly experience mild symptoms or are asymptomatic. Ducks have a unique, innate immune system hypothesized to induce antiviral responses. Circular RNAs (circRNAs) are among the most abundant and conserved eukaryotic transcripts. These participate in innate immunity and host antiviral response progression. Methods: In this study, circRNA expression profile differences post-NDV infection in duck embryo fibroblast (DEF) cells were analyzed using circRNA transcriptome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to reveal significant enrichment of differentially expressed (DE) circRNAs. The circRNA-miRNA-mRNA interaction networks were used to predict the related functions of circRNAs. Moreover, circ-FBXW7 was selected to determine its effect on NDV infection in DEFs. Results: NDV infection altered circRNA expression profiles in DEF cells, and 57 significantly differentially expressed circRNAs were identified post-NDV infection. DEF responded to NDV by forming circRNAs to regulate apoptosis-, cell growth-, and protein degradation-related pathways via GO and KEGG enrichment analyses. circRNA-miRNA-mRNA interaction networks demonstrated that DEF cells combat NDV infection by regulating cellular pathways or apoptosis through circRNA-targeted mRNAs and miRNAs. circ-FBXW7 overexpression and knockdown inhibited and promoted viral replication, respectively. DEF cells mainly regulated cell cycle alterations or altered cellular sensing to combat NDV infection. Conclusion: These results demonstrate that DEF cells exert antiviral responses by forming circRNAs, providing novel insights into waterfowl antiviral responses.

20.
Chemosphere ; 340: 139912, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37611761

RESUMO

Because of the unstable wastewater quantity and quality, the biological treatment efficiency of digested effluent was not as expected. A convenient and effective way was eagerly required to improve the efficiency of biological treatment. By sheet iron addition (R1), the COD and TN removal efficiencies under continuous flow condition increased by 59% and 37% respectively. The bulk pH maintained at around 7.5 which benefited most bacteria, while in the control (R0, without sheet iron addition) the pH decreased to 5.0. Both chemical and bio-removal of COD existed in R1, but the chemical removal dominated (63.71%). The enhanced COD removal efficiency came from the chemical oxidation by Fe3+ (47.43%) and Fe0 (10.86%). For the TN removal, the enhancement mainly came from the improvement of anammox activity by Fe3+ (14.87%), the bio-oxidation of ammonium with Fe3+ as electron acceptor (8.78%), and the bio-reduction of nitrate/nitrite with Fe2+ and H2 as electron donor (35.76%). By the first-order kinetic fitting analysis, the COD and TN removal rate in R1 was higher than that in R0. Thus, for a quick and high COD and TN removal from digested effluent, the addition of Fe0/Fe2+/Fe3+ was suggested, and the best form should be Fe0 (e.g., sheet iron). The addition of sheet iron reduces the cost of nitrogen removal and improves the efficiency of COD and TN removal. Comparing with the combined processes, this novel approach has potential advantages with simple operation and high efficiency. It endows the biological process much broader application in digested effluent treatment.


Assuntos
Ferro , Nitrogênio , Cinética , Oxidantes , Águas Residuárias
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