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  • Frontiers Media SA  (181)
  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-4-12)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-4-12)
    Abstract: Idiopathic pulmonary fibrosis is a progressive lung disease with high mortality and limited therapy that is characterized by epithelial cell damage and fibroblast activation. Ellagic acid is a natural polyphenol compound widely found in fruits and nuts that has multiple pharmacological activities. In this study, we explored the potential effects and mechanisms of Ellagic acid on pulmonary fibrosis in vivo and in vitro . In vivo studies showed that Ellagic acid significantly alleviated bleomycin (BLM)-induced pulmonary fibrosis in mice. In vitro experiments indicated that Ellagic acid could suppress Wnt signaling and attenuate Wnt3a-induced myofibroblast activation and the phosphorylation of Erk2 and Akt. Further studies showed that Ellagic acid could induce autophagy formation in myofibroblasts mainly by suppressing mTOR signaling and promoting apoptosis of myofibroblasts. In vivo experiments revealed that Ellagic acid significantly inhibited myofibroblast activation and promoted autophagy formation. Taken together, our results show that Ellagic acid effectively attenuates BLM-induced pulmonary fibrosis in mice by suppressing myofibroblast activation and promoting autophagy and apoptosis of myofibroblasts by inhibiting the Wnt signaling pathway.
    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
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2019
    In:  Frontiers in Plant Science Vol. 10 ( 2019-2-19)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 10 ( 2019-2-19)
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Genetics Vol. 12 ( 2022-1-3)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 12 ( 2022-1-3)
    Abstract: Pancreatic adenocarcinoma is one of the leading causes of cancer-related death worldwide. Since little clinical symptoms were shown in the early period of pancreatic adenocarcinoma, most patients were found to carry metastases when diagnosis. The lack of effective diagnosis biomarkers and therapeutic targets makes pancreatic adenocarcinoma difficult to screen and cure. The fundamental problem is we know very little about the regulatory mechanisms during carcinogenesis. Here, we employed weighted gene co-expression network analysis (WGCNA) to build gene interaction network using expression profile of pancreatic adenocarcinoma from The Cancer Genome Atlas (TCGA). STRING was used for the construction and visualization of biological networks. A total of 22 modules were detected in the network, among which yellow and pink modules showed the most significant associations with pancreatic adenocarcinoma. Dozens of new genes including PKMYT1, WDHD1, ASF1B, and RAD18 were identified. Further survival analysis yielded their valuable effects on the diagnosis and treatment of pancreatic adenocarcinoma. Our study pioneered network-based algorithm in the application of tumor etiology and discovered several promising regulators for pancreatic adenocarcinoma detection and therapy.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606823-0
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-6-22)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-6-22)
    Abstract: Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin lymphoma with a poor prognosis. We aimed to evaluate the prognostic impact of circulating NK cells in PCNSL. Materials and methods Patients diagnosed with PCNSL who were treated at our institution between December 2018 and December 2019 were retrospectively screened. Patient variables including age, sex, Karnofsky performance status, diagnostic methods, location of lesions, lactate dehydrogenase, cerebrospinal fluids (CSF), and vitreous fluids involvement or not were documented. NK cell count and NK cell proportion (NK cell count/lymphocyte count) in the peripheral blood were evaluated by flow cytometry. Some patients underwent two consecutive NK cell tests before and three weeks after chemotherapy (before the next chemotherapy). The fold change in NK cell proportion and NK cell counts were calculated. CD56-positive NK cells in tumor tissue were assessed by immunohistochemistry. NK cell cytotoxicity assay was performed using flow cytometry. Results A total of 161 patients with PCNSL were included in this study. The median NK cell count of all NK cell tests was 197.73/μL (range 13.11–1889.90 cells/μL). The median proportion of NK cells was 14.11% (range 1.68–45.15%) for all. Responders had a higher median NK cell count ( p & lt;0.0001) and NK cell proportion ( p & lt;0.0001) than non-responders. Furthermore, Responders had a higher median fold change in NK cell proportion than non-responders ( p =0.019) or patients in complete remission/partial remission ( p & lt;0.0001). A higher median fold change in NK cell count was observed in responders than in non-responders ( p =0.0224) or patients in complete remission/partial remission ( p =0.0002). For newly diagnosed PCNSL, patients with a high NK cell count ( & gt;165 cells/μL) appeared to have a longer median overall survival than those with a low NK cell count ( p =0.0054). A high fold change in the proportion of NK cells ( & gt;0.1957; p =0.0367) or NK cell count ( & gt;0.1045; p =0.0356) was associated with longer progression-free survival. Circulating NK cells from newly-diagnosed PCNSL demonstrated an impaired cytotoxicity capacity compared to those from patients with PCNSL in complete remission or healthy donors. Conclusion Our study indicated that circulating NK cells had some impact on the outcome of PCNSL.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-6-24)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-6-24)
    Abstract: The MDM2 binding protein (MTBP) has been considered an important regulator of human malignancies. In this study, we demonstrate that the high level of MTBP’s endogenous expression is correlated with poor prognosis of advanced hepatocellular carcinoma (HCC) patients who received sorafenib. MTBP interacted with the Pregnane X receptor (PXR) and enhanced the transcription factor activity of PXR. Moreover, MTBP enhanced the accumulation of PXR in HCC cells’ nuclear and the recruitment of PXR to its downstream gene’s ( cyp3a4’s ) promoter region. Mechanically, the knockdown of MTBP in MHCC97-H cells with high levels of MTBP decelerated the clearance or metabolism of sorafenib in HCC cells and led to the resistance of HCC cells to sorafenib. Whereas overexpression of MTBP in in MHCC97-L cells with low levels of MTBP showed the opposite trend. By establishing the interaction between MTBP and PXR, our results indicate that MTBP could function as a co-activator of PXR and could be a promising therapeutic target to enhance the sensitivity of HCC cells to molecular targeting agents.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 6
    In: Frontiers in Environmental Science, Frontiers Media SA, Vol. 10 ( 2023-1-10)
    Abstract: Most plant‒soil feedback studies have been conducted on the mechanism by which soil directly influences plant growth performance and mostly in indoor pot experiments; however, it is unclear how plant‒soil feedback is influenced by plant, soil and microbial diversity in grassland ecosystems in alpine meadows with high plant diversity. In this study, plant‒soil feedback patterns were investigated by analyzing plant, soil and microbial characteristics across seven gradients in the time series from light degradation to 10-years of recovery, classified into three categories: ecosystem multifunctionality, biotic and abiotic factors, and comparing the strength and magnitude of plant‒soil feedback in alpine meadows of degradation stages and years of recovery. The results showed that the plant-soil feedback relationships in alpine meadows differed significantly in three aspects: ecosystem multifunctionality, biotic and abiotic factors in the degradation stage and recovery years, and under the degradation gradient, ecosystem multifunctionality decreased from 0.34 to −0.99 with the deepening of degradation, biotic factors increased from −0.17 to 0.09, and abiotic factors increased from −0.17 to 0.15, while in the recovery gradient, ecosystem multifunctionality showed a trend of increasing and then decreasing with increasing recovery years, while biotic and abiotic factors showed fluctuating changes. The plant-soil feedback index indicated that the strength and direction of plant-soil interactions during degradation and recovery were different, and the positive feedback effect was 0.34 and 0.38 in the early stage of degradation and recovery, respectively, which were greater than the negative feedback effect. With the deepening of degradation, the negative feedback effect became more and more obvious, and at the stage of extreme degradation, the negative feedback effect reached −0.99, which was much larger than the positive feedback effect. However, with the increase of the recovery years, the positive feedback effect gradually weakened, and finally all of them were negative feedback effects at 10-years of recovery. This study provides a scientific basis for understanding plant-soil feedback in alpine meadow ecosystems and indicates the direction for the next scientific recovery of alpine meadows.
    Type of Medium: Online Resource
    ISSN: 2296-665X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2741535-1
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-11-2)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-11-2)
    Abstract: There are technical obstacles in the safety evaluation of traditional Chinese medicine (TCM) injections due to their complex chemical nature and the lack of rapid and accurate in vitro methods. Here, we established a dual in vitro mitochondrial toxicity approach combing the conventional “glucose/galactose” assay in HepG2 cells with the cytotoxic assay in mitochondrial respiration deficient cells. Using this dual in vitro approach, for the first time, we systematically assessed the mitochondrial toxicity of TCM injections. Four of the 35 TCM injections, including Xiyanping, Dengzhanhuasu, Shuanghuanglian, and Yinzhihuang, significantly reduced cellular ATP production in galactose medium in the first assay, and presented less cytotoxic in the respiration deficient cells in the second assay, indicating that they have mitochondrial toxicity. Furthermore, we identified scutellarin, rutin, phillyrin, and baicalin could be the potential mitochondrial toxic ingredients in the 4 TCM injections by combining molecular docking analysis with experimental validation. Collectively, the dual in vitro approach is worth applying to the safety evaluation of more TCM products, and mitochondrial toxic TCM injections and ingredients found in this study deserve more attention.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 8
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 10 ( 2019-3-8)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2606827-8
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  • 9
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-7-11)
    Abstract: The prognosis of relapsed/refractory (R/R) primary central nervous system lymphoma (PCNSL) is dismal, and there are limited treatment options for these patients. This was a prospective single-arm phase II study of combined pemetrexed and lenalidomide for salvage treatment of R/R PCNSL. Patients with R/R PCNSL (n = 38) who had undergone two or more different therapeutic regimens and experienced disease progression or recurrence were enrolled. The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Patients were followed up for a median of 18 (range, 1–36) months. ORR was 68.4%, with median PFS and OS of 6 and 18 months, respectively. Adverse events (AEs) included myelosuppression, fatigue, nausea, fever, infection, cardiac disease, and thrombogenesis. Commonly observed grade ≥ 3 AEs included neutropenia (5.3%), leukopenia (2.6%), thrombocytopenia (7.9%), and infection (2.6%). Elevated lactate dehydrogenase (LDH) levels (χ 2 = 13.25; P = 0.0003) and bulky disease (P = 0.032; χ 2 = 4.580) were associated with short PFS. Elevated serum LDH level (P = 0.011; χ 2 = 6.560), abnormal lymphoma cells in the cerebrospinal fluid (CSF) [P = 0.011; χ 2 = 6.445], and multiple lesions (P = 0.036; χ 2 = 4.404) were significantly associated with poorer OS. Abnormal lymphoma cells in the CSF were an independent predictor of poor prognosis on multivariate analysis (P = 0.034; hazard ratio (HR) = 2.836; 95% confidence interval, 1.082–7.434). Our results indicate that pemetrexed plus lenalidomide is effective for heavily treated R/R PCNSL, with moderate toxicity. Trial registration: #ChiCTR1900028070.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Plant Science Vol. 12 ( 2021-5-13)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 12 ( 2021-5-13)
    Abstract: Glycerol-3-phosphate acyltransferases (GPATs), critical for multiple biological processes like male fertility, have been extensively characterized. However, their precise functions and underlying regulatory mechanism in cotton anther development are unclear. This research demonstrated the importance of GhGPAT12 / 25 (a paralogs pair on A12/D12 sub-chromosome of cotton) to regulate the degradation of tapetum, anther cuticle formation, and pollen exine development. GhGPAT12 and GhGPAT25 exhibited specifically detected transcripts in tapetum and pollen exine during the early anther developmental stages. GhGPAT12/25 are sn-2 glycerol-3-phosphate acyltransferases and can transfer the acyl group of palmitoyl-CoA to glycerol-3-phosphate (G3P). CRISPR/Cas9-mediated knockout identified the functional redundancy of GhGPAT12 and GhGPAT25 . Knockout of both genes caused completely male sterility associated with abnormal anther cuticle, swollen tapetum, and inviable microspores with defective exine and irregular unrestricted shape. RNA-seq analysis showed that the loss of function of GhGPAT12 / 25 affects the processes of wax metabolic, glycerol monomer biosynthesis, and transport. Consistently, cuticular waxes were dramatically reduced in mutant anthers. Yeast one-hybrid system (Y1H), virus-induced gene silencing (VIGS), and dual-luciferase (LUC) assays illustrated that GhMYB80s are likely to directly activate the expression of GhGPAT12 / 25 . This study provides important insights for revealing the regulatory mechanism underlying anther development in cotton.
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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