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  • Frontiers Media SA  (5)
  • Wu, Tong  (5)
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  • Frontiers Media SA  (5)
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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-2-18)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-2-18)
    Abstract: Background and Purpose: Activation of hepatic stellate cells (HSC) is a central driver of liver fibrosis. 5-lipoxygenase (5-LO) is the key enzyme that catalyzes arachidonic acid into leukotrienes. In this study, we examined the role of 5-LO in HSC activation and liver fibrosis. Main Methods: Culture medium was collected from quiescent and activated HSC for target metabolomics analysis. Exogenous leukotrienes were added to culture medium to explore their effect in activating HSC. Genetic ablation of 5-LO in mice was used to study its role in liver fibrosis induced by CCl 4 and a methionine-choline-deficient (MCD) diet. Pharmacological inhibition of 5-LO in HSC was used to explore the effect of this enzyme in HSC activation and liver fibrosis. Key Results: The secretion of LTB 4 and LTC 4 was increased in activated vs. quiescent HSC. LTB 4 and LTC 4 contributed to HSC activation by activating the extracellular signal-regulated protein kinase pathway. The expression of 5-LO was increased in activated HSC and fibrotic livers of mice. Ablation of 5-LO in primary HSC inhibited both mRNA and protein expression of fibrotic genes. In vivo , ablation of 5-LO markedly ameliorated the CCl 4 - and MCD diet-induced liver fibrosis and liver injury. Pharmacological inhibition of 5-LO in HSC by targeted delivery of the 5-LO inhibitor zileuton suppressed HSC activation and improved CCl 4 - and MCD diet-induced hepatic fibrosis and liver injury. Finally, we found increased 5-LO expression in patients with non-alcoholic steatohepatitis and liver fibrosis. Conclusion: 5-LO may play a critical role in activating HSC; genetic ablation or pharmacological inhibition of 5-LO improved CCl 4 -and MCD diet-induced liver fibrosis.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-5-28)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-5-28)
    Abstract: To develop and validate a simple-to-use prognostic scoring model based on clinical and pathological features which can predict overall survival (OS) of patients with oral squamous cell carcinoma (OSCC) and facilitate personalized treatment planning. Materials and Methods OSCC patients (n = 404) from a public hospital were divided into a training cohort (n = 282) and an internal validation cohort (n = 122). A total of 12 clinical and pathological features were included in Kaplan–Meier analysis to identify the factors associated with OS. Multivariable Cox proportional hazards regression analysis was performed to further identify important variables and establish prognostic models. Nomogram was generated to predict the individual’s 1-, 3- and 5-year OS rates. The performance of the prognostic scoring model was compared with that of the pathological one and the AJCC TNM staging system by the receiver operating characteristic curve (ROC), concordance index (C-index), calibration curve, and decision curve analysis (DCA). Patients were classified into high- and low-risk groups according to the risk scores of the nomogram. The nomogram-illustrated model was independently tested in an external validation cohort of 95 patients. Results Four significant variables (physical examination-tumor size, imaging examination-tumor size, pathological nodal involvement stage, and histologic grade) were included into the nomogram-illustrated model (clinical–pathological model). The area under the ROC curve (AUC) of the clinical–pathological model was 0.687, 0.719, and 0.722 for 1-, 3- and 5-year survival, respectively, which was superior to that of the pathological model (AUC = 0.649, 0.707, 0.717, respectively) and AJCC TNM staging system (AUC = 0.628, 0.668, 0.677, respectively). The clinical–pathological model exhibited improved discriminative power compared with pathological model and AJCC TNM staging system (C-index = 0.755, 0.702, 0.642, respectively) in the external validation cohort. The calibration curves and DCA also displayed excellent predictive performances. Conclusion This clinical and pathological feature based prognostic scoring model showed better predictive ability compared with the pathological one, which would be a useful tool of personalized accurate risk stratification and precision therapy planning for OSCC patients.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2019
    In:  Frontiers in Pharmacology Vol. 10 ( 2019-5-28)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 10 ( 2019-5-28)
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-5-11)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-5-11)
    Abstract: Chromobox family genes (CBXs) are known to play roles in numerous modifications of the chromatin in order to inhibit the transcription of target genes. CBXs have been shown to be expressed at high levels in many types of cancer and can also serve as a target gene for therapeutic purposes. However, little is known about the expression and prognostic value of CBXs in human sarcomas. Methods The transcription level of CBXs was analyzed using the Oncomine dataset, and the differential expression of CBXs in sarcoma was reported by the Gene Expression Profiling Interactive Analysis (GEPIA) dataset. We also used the CCLE dataset to evaluate the expression of CBXs in a sarcoma cell line. The prognostic value of CBXs was analyzed using GEPIA and Kaplan–Meier analysis. In addition, the corrections between CBXs and their co-expressed genes were reported using Oncomine and GEPIA datasets. DAVID was used to perform GO function enrichment analysis for the CBXs and their co-expression genes. Finally, TIMER was used to analyze the immune cell infiltration of CBXs in patients with sarcoma. Results HP1- α/β/γ (CBX1/3/5) and CBX4/6/8 were found to be overexpressed in human sarcoma, and CBXs were upregulated in almost all the sarcoma cell line. The expression levels of HP1- α/β/γ (CBX1/3/5) and CBX7 were associated with overall survival (OS) in patients with sarcoma, while high expression levels of CBX7 were related to disease-free survival (DFS). In addition, the expression levels of CBX2/6/7 were related to recurrence-free survival (RFS). We also found that the CBX family was positively correlated with the infiltration of immune cells, including CD8 + T cells, CD4 + T cells, B cells, macrophages, neutrophils, and dendritic cells, in sarcoma. Conclusions The results from the present study indicated that CBXs were significantly associated with prognosis and immunological status in sarcoma. These data suggest that CBXs could serve as potential biomarkers for prognosis and immune infiltration in human sarcoma.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
    Location Call Number Limitation Availability
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-8-11)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-8-11)
    Abstract: Staphylococcus xylosus ( S. xylosus ) has become an emerging opportunistic pathogen due to its strong biofilm formation ability. Simultaneously, the biofilm of bacteria plays an important role in antibiotic resistance and chronic infection. Here, we confirmed that rutin can effectively inhibit biofilm formation in S. xylosus , of which the inhibition mechanism involves its ability to interact with imidazole glycerol phosphate dehydratase (IGPD), a key enzyme in the process of biofilm formation. We designed experiments to target IGPD and inhibited its activities against S. xylosus . Our results indicated that the activity of IGPD and the amount of histidine decreased significantly under the condition of 0.8 mg/ml rutin. Moreover, the expression of IGPD mRNA ( hisB ) and IGPD protein was significantly down-regulated. Meanwhile, the results from molecular dynamic simulation and Bio-layer interferometry (BLI) technique showed that rutin could bind to IGPD strongly. Additionally, in vivo studies demonstrated that rutin treatment reduced inflammation and protect mice from acute mastitis caused by S. xylosus . In summary, our findings provide new insights into the treatment of biofilm mediated persistent infections and chronic bacterial infections. It could be helpful to design next generation antibiotics to against resistant bacteria.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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