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1.
Ecotoxicol Environ Saf ; 281: 116661, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38954907

RESUMO

OBJECTIVE: Baicalin has antioxidative, antiviral, and anti-inflammatory properties. However, its ability to alleviate oxidative stress (OS) and DNA damage in liver cells exposed to aflatoxin B1 (AFB1), a highly hepatotoxic compound, remains uncertain. In this study, the protective effects of baicalin on AFB1-induced hepatocyte injury and the mechanisms underlying those effects were investigated. METHODS: Stable cell lines expressing CYP3A4 were established using lentiviral vectors to assess oxidative stress levels by conducting assays to determine the content of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Additionally, DNA damage was evaluated by 8-hydroxy-2-deoxyguanosine (8-OHdG) and comet assays. Transcriptome sequencing, molecular docking, and in vitro experiments were conducted to determine the mechanisms underlying the effects of baicalin on AFB1-induced hepatocyte injury. In vivo, a rat model of hepatocyte injury induced by AFB1 was used to evaluate the effects of baicalin. RESULTS: In vitro, baicalin significantly attenuated AFB1-induced injury caused due to OS, as determined by a decrease in ROS, MDA, and SOD levels. Baicalin also considerably decreased AFB1-induced DNA damage in hepatocytes. This protective effect of baicalin was found to be closely associated with the TP53-mediated ferroptosis pathway. To elaborate, baicalin physically interacts with P53, leading to the suppression of the expression of GPX4 and SLC7A11, which in turn inhibits ferroptosis. In vivo findings showed that baicalin decreased DNA damage and ferroptosis in AFB1-treated rat liver tissues, as determined by a decrease in the expression of γ-H2AX and an increase in GPX4 and SLC7A11 levels. Overexpression of TP53 weakened the protective effects of baicalin. CONCLUSIONS: Baicalin can alleviate AFB1-induced OS and DNA damage in liver cells via the TP53-mediated ferroptosis pathway. In this study, a theoretical foundation was established for the use of baicalin in protecting the liver from the toxic effects of AFB1.


Assuntos
Aflatoxina B1 , Ferroptose , Flavonoides , Hepatócitos , Proteína Supressora de Tumor p53 , Flavonoides/farmacologia , Aflatoxina B1/toxicidade , Ferroptose/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Animais , Proteína Supressora de Tumor p53/metabolismo , Ratos , Estresse Oxidativo/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Masculino , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Humanos , Espécies Reativas de Oxigênio/metabolismo
2.
Acad Radiol ; 31(7): 2775-2783, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38177032

RESUMO

RATIONALE AND OBJECTIVES: The use of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) in assessing inflammatory diseases has shown significant promise. Uptake patterns in perianal fistulas, which may be an incidental finding on PET/CT, have not been purposefully studied. Our aim was to compare FDG uptake of perianal fistulas to that of the liver and anal canal in patients who underwent PET/CT for hematologic/oncologic diagnosis or staging. MATERIALS AND METHODS: We retrospectively identified patients who underwent FDG-PET/CT imaging between January 2011 and May 2023, where the report described a perianal fistula or abscess. PET/CTs of patients included in the study were retrospectively analyzed to record the maximum standardized uptake value (SUVmax) of the fistula, abscess, anal canal, rectum, and liver. Fistula-to-liver and Fistula-to-anus SUVmax ratios were calculated. We statistically compared FDG activity among the fistula, liver, and anal canal. We also assessed FDG activity in patients with vs. without anorectal cancer, as well as across different St. James fistula grades. RESULTS: The study included 24 patients with identifiable fistulas. Fistula SUVmax (mean=10.8 ± 5.28) was significantly higher than both the liver (mean=3.09 ± 0.584, p < 0.0001) and the anal canal (mean=5.98 ± 2.63, p = 0.0005). Abscess fistula SUVmax was 15.8 ± 4.91. St. James grade 1 fistulas had significantly lower SUVmax compared to grades 2 and 4 (p = 0.0224 and p = 0.0295, respectively). No significant differences existed in SUVmax ratios between anorectal and non-anorectal cancer groups. CONCLUSION: Perianal fistulas have increased FDG avidity with fistula SUVmax values that are significantly higher than the anal canal.


Assuntos
Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Fístula Retal , Humanos , Fluordesoxiglucose F18/farmacocinética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Masculino , Feminino , Compostos Radiofarmacêuticos/farmacocinética , Pessoa de Meia-Idade , Fístula Retal/diagnóstico por imagem , Adulto , Idoso , Canal Anal/diagnóstico por imagem , Fígado/diagnóstico por imagem , Fígado/metabolismo
3.
Heliyon ; 10(1): e23923, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38223741

RESUMO

Objective: Pre-treatment enhanced CT image data were used to train and build models to predict the efficacy of non-small cell lung cancer after conventional radiotherapy and chemotherapy using two classification algorithms, Logistic Regression (LR) and Gaussian Naive Baye (GNB). Methods: In this study, we used pre-treatment enhanced CT image data for region of interest (ROI) sketching and feature extraction. We utilized the least absolute shrinkage and selection operator (LASSO) mutual confidence method for feature screening. We pre-screened logistic regression (LR) and Gaussian naive Bayes (GNB) classification algorithms and trained and modeled the screened features. We plotted 5-fold and 10-fold cross-validated receiver operating characteristic (ROC) curves to calculate the area under the curve (AUC). We performed DeLong's test for validation and plotted calibration curves and decision curves to assess model performance. Results: A total of 102 patients were included in this study, and after a comparative analysis of the two models, LR had only slightly lower specificity than GNB, and higher sensitivity, accuracy, AUC value, precision, and F1 value than GNB (training set accuracy: 0.787, AUC value: 0.851; test set accuracy: 0.772, AUC value: 0.849), and the LR model has better performance in both the decision curve and the calibration curve. Conclusion: CT can be used for efficacy prediction after radiotherapy and chemotherapy in NSCLC patients. LR is more suitable for predicting whether NSCLC prognosis is in remission without considering the computing speed.

4.
Int Immunopharmacol ; 127: 111416, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38145599

RESUMO

BACKGROUND: Synovial chondromatosis (SC) primarily affects the major joints and is characterized by the formation of benign cartilaginous nodules. In the present study, we evaluated the differences in the histology and gene expression of SC and normal cartilages and further elucidated the function of hub genes in SC. METHODS: Histological staining and biochemical analysis were performed to measure collagen and glycosaminoglycan (GAG) contents in SC and normal cartilage samples. Then, microarray analysis was performed using knee joint samples (three normal and three SC samples) to identify the differentially expressed genes (DEGs). Subsequently, bioinformatics analysis was performed to identify the hub genes and explore the mechanisms underlying SC. The intersection of the top 10 upregulated DEGs, top 10 downregulated DEGs, and hub genes was validated in SC tissues. Lastly, in vitro experiments and our clinical cohort were used to determine the potential biological functions and diagnostic value, respectively, of the most significant gene. RESULTS: The GAG and collagen contents were comparable to or higher in SC tissues than in normal tissues. Microarray analysis revealed 143 upregulated and 107 downregulated DEGs in SC. Furthermore, functional enrichment analysis revealed an association between immunity and metabolism-related pathways and SC development. Among 20 hub genes, two intersection genes, namely, collagen type III alpha 1 chain (COL3A1) and HSPA8, were notably expressed in SC tissues, with COL3A1 exhibiting a more significant difference in mRNA expression. Furthermore, COL3A1 can promote chondrocyte migration and cell cycle progression. Additionally, clinical data revealed COL3A1 can be a diagnostic marker for primary SC (AUC = 0.82) and be a positive correlation with neutrophil-to-lymphocyte ratio. CONCLUSIONS: These results suggest that SC tissues contained the abundant GAG and collagen. COL3A1 can affect the function of chondrocytes and be a diagnostic marker of primary SC patients. These findings provide a novel approach and a fundamental contribution for diagnosis and treatment in SC.


Assuntos
Condrócitos , Condromatose Sinovial , Humanos , Condrócitos/patologia , Condromatose Sinovial/patologia , Biomarcadores , Ciclo Celular/genética , Colágeno , Biologia Computacional/métodos , Colágeno Tipo III
5.
Cell Cycle ; 21(4): 323-339, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34974804

RESUMO

Intervertebral disc degeneration (IDD) constitutes the pathological foundation of most musculoskeletal disorders of the spine. Previous studies have noted that cell proliferation is a common feature of IDD. Bioinformatics indicated that aberrantly expressed long non-coding RNAs (lncRNAs) were involved in the development of IDD. In this study, we aimed to investigate the function of lncRNA HOTAIR in the proliferation of human nucleus pulposus (NP) cells of IDD in vitro and further clarified its mechanism. The expression of HOTAIR and miR-130b was quantified by qRT-PCR in nucleus pulposus (NP) tissues. Furthermore, NP cells proliferation were assayed by CCK8 and Immunostaining. Dual-luciferase reporter and RIP assay were used to examine the expression of HOTAIR, PTEN, and their co-target gene miR-130b. Western blotting was used to test AKT expression. Our in vitro experiments on human normal NP cells observed that HOTAIR was significantly dysregulated in IDD. Further, HOTAIR can suppress proliferation by directly targeting miR-130b. In addition, Both HOTAIR and PTEN were confirmed to target miR-130b, and miR-130b upregulation reversed the phenomenon of ectopic expression of HOTAIR. More importantly, HOTAIR upregulation significantly reduced CyclinD1 protein expression by PTEN/AKT signaling pathway. Our findings suggest that HOTAIR may bind to miR-130b and subsequently increased CyclinD1 expression via PTEN/Akt pathway. Thereby, HOTAIR could become a potential target for the treatment of IDD.Abbreviations : IDD; intervertebral disc degeneration ncRNAs; non-coding RNAs lncRNAs; long non-coding RNAs miRNAs; microRNAs NP; nucleus pulposus qRT-PCR; quantitative reverse transcription-PCR LBP; Low back pain ORF; open reading frame HOTAIR; Hox transcript antisense intergenic RNA FAF1; Fas-associated protein factor-1 Erk; extracellular signal-regulated kinase TUG1; Taurine Up-regulated Gene 1 HIF1A hypoxia-inducible factor 1-alpha PI3K; phosphoinositide-3 kinase AIS; adolescent idiopathic scoliosis ECM; extracellular matrix LN;lupus nephritis CT;computed tomography MRI; magnetic resonance imaging PBS; phosphate-buffered salin PBS; phosphate-buffered salin PVDF; polyvinylidene fluoride TBST; Tris-buffered saline Tween ECL; enhanced chemiluminescence RIP; RNA immunoprecipitation.


Assuntos
Degeneração do Disco Intervertebral , MicroRNAs , RNA Longo não Codificante/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proliferação de Células/genética , Humanos , Degeneração do Disco Intervertebral/patologia , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosfatos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
6.
Chem Biodivers ; 13(2): 241-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26880438

RESUMO

The aerial parts of Ocimum basilicum L. were collected from four different geographical locations, Sindhuli and Biratnagar (Nepal), Chormaghzak village (Tajikistan), and Sana'a (Yemen). The essential oils were obtained by hydrodistillation and analyzed by gas chromatography/mass spectrometry. A cluster analysis of 179 essential oil compositions revealed six major chemotypes: Linalool, eugenol, estragole, methyl eugenol, 1,8-cineole, and geraniol. All four of the basil oils in this study were of the linalool-rich variety. Some of the basil oils were screened for bioactivity including antimicrobial, cytotoxicity in human cancer cells, brine shrimp lethality, nematicidal, larvicidal, insecticidal, and antioxidant. The basil oils in this study were not notably antibacterial, cytotoxic, antioxidant, nor nematicidal, but were active in the brine shrimp lethality test, and did show larvicidal and insecticidal activities.


Assuntos
Ocimum basilicum/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Componentes Aéreos da Planta/química , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Artemia/efeitos dos fármacos , Linhagem Celular Tumoral , Análise por Conglomerados , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Inseticidas/química , Inseticidas/farmacologia , Nepal , Tadjiquistão , Iêmen
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