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  • Online-Ressource  (11)
  • Frontiers Media SA  (11)
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  • Online-Ressource  (11)
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  • Frontiers Media SA  (11)
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  • 1
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-10-4)
    Kurzfassung: Lung cancer is the most common tumor worldwide, with the highest mortality rate and second highest incidence. Immunotherapy is one of the most important treatments for lung adenocarcinoma (LUAD); however, it has relatively low response rate and high incidence of adverse events. Herein, we explored the therapeutic potential of fibrinogen-like protein 1 (FGL1) for LUAD. Methods Data from GEPIA and ACLBI databases were assessed to explore gene–gene correlations and tumor immune infiltration patterns. A total of 200 patients with LUAD were recruited. FGL1 levels in the serum and cellular supernatant were determined by enzyme-linked immunosorbent assay. In vitro and in vivo experiments were performed to assess the effect FGL1 on the proliferation of LUAD cells. Cocultures were performed to explore the effect of FGL1 knockdown in lung cancer cells on T cells, concerning cytokine secretion and viability. PROMO and hTFtarget databases were used for transcription factor prediction. Quantitative polymerase chain reaction (qPCR), chromatin immunoprecipitation, and dual luciferase reporter assays were performed to validate the identified transcription factor of FGL1. Immunoprecipitation, mass spectrometry and gene ontology analysis were performed to explore the downstream partners of FGL1. Results FGL1 expression in LUAD was positively associated with PDL1 , but not for PD1 expression. Moreover, FGL1 was positively associated with the CD3D expression and negatively associated with FOXP3 , S100A9 , and TPSB2 within the tumor site. FGL1 promotes the secretion of interleukin-2 by T cells in vitro , simultaneously inducing their apoptosis. Indeed, YY1 is the upstream molecule of FGL1 was found to be transcriptionally regulated by YY1 and to directly by to MYH9 to promote the proliferation of LUAD cells in vitro and in vivo . Conclusions FGL1 is involved in the immunological and proliferative regulation of LUAD cells by controlling the secretion of important immune-related cytokines via the YY1–FGL1–MYH9 axis. Hence, targeting FGL1 in LUAD may pave the way for the development of new immunotherapies for tackling this malignancy.
    Materialart: Online-Ressource
    ISSN: 1664-3224
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2606827-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2023
    In:  Frontiers in Neuroscience Vol. 16 ( 2023-1-11)
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 16 ( 2023-1-11)
    Kurzfassung: Most previous studies on acupuncture in the treatment of knee osteoarthritis (KOA) have focused on improving functional efficacy and safety, while related mechanisms have not been systematically reviewed. Acupuncture modulates cytokines to attenuate cartilage extracellular matrix degradation and apoptosis, key to the pathogenesis of KOA, but the mechanisms are complex. Objectives The purpose of this study is to assess the efficacy of acupuncture quantitatively and summarily in animal studies of KOA. Methods Nine databases including PubMed, Embase, Web of Science (including Medline), Cochrane library, Scopus, CNKI, Wan Fang, and VIP were searched to retrieve animal studies on acupuncture interventions in KOA published since the inception of the journal. Relevant literature was screened, and information extracted. Meta-analysis was performed using Revman 5.4 and Stata 17.0 software. Results The 35 included studies involved 247 animals, half of which were in acupuncture groups and half in model groups. The mean quality level was 6.7, indicating moderate quality. Meta-analysis showed that acupuncture had the following significant effects on cytokine levels in p38MAPK and mitochondrial pathways: (1) p38MAPK pathway: It significantly inhibits p38MAPK, interleukin-1beta (IL-1β), tumor necrosis factor alpha (TNF-α), phosphorylated (p)-p38MAPK, matrix metalloproteinase-13 (MMP-13), MMP-1, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMST-5) expression, and significantly increased the expression of collagen II and aggrecan. (2) mitochondrial pathway: It significantly inhibited the expression of Bcl-2-associated X protein (Bax), cysteine protease-3 (caspase-3), caspase-9, and Cytochrome-c (Cyt-c). And significantly increased the expression of B cell lymphocytoma-2 (Bcl-2). In addition, acupuncture significantly reduced chondrocyte apoptosis, Mankin’s score (a measure of cartilage damage), and improved cartilage morphometric characteristics. Conclusion Acupuncture may inhibit cytokine expression in the p38MAPK pathway to attenuate cartilage extracellular matrix degradation, regulate cytokines in the mitochondrial pathway to inhibit chondrocyte apoptosis, and improve cartilage tissue-related phenotypes to delay cartilage degeneration. These findings provide possible explanations for the therapeutic mechanisms and clinical benefits of acupuncture for KOA. Systematic review registration https://inplasy.com , identifier INPLASY20 2290125.
    Materialart: Online-Ressource
    ISSN: 1662-453X
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2023
    ZDB Id: 2411902-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 11 ( 2020-2-4)
    Materialart: Online-Ressource
    ISSN: 1663-9812
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2020
    ZDB Id: 2587355-6
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-5-11)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-5-11)
    Kurzfassung: Sepsis is a leading cause of morbidity and mortality in the intensive care unit, which is caused by unregulated inflammatory response leading to organ injuries. Ulinastatin (UTI), an immunomodulatory agent, is widely used in clinical practice and is associated with improved outcomes in sepsis. But its underlying mechanisms are largely unknown. Our study integrated bulk and single cell RNA-seq data to systematically explore the potential mechanisms of the effects of UTI in sepsis. After adjusting for potential confounders in the negative binomial regression model, there were more genes being downregulated than being upregulated in the UTI group. These down-regulated genes were enriched in the neutrophil involved immunity such as neutrophil activation and degranulation, indicating the immunomodulatory effects of UTI is mediated via regulation of neutrophil activity. By deconvoluting the bulk RNA-seq samples to obtain fractions of cell types, the Myeloid-derived suppressor cells (MDSC) were significantly expanded in the UTI treated samples. Further cell-cell communication analysis revealed some signaling pathways such as ANEEXIN, GRN and RESISTIN that might be involved in the immunomodulatory effects of UTI. The study provides a comprehensive reference map of transcriptional states of sepsis treated with UTI, as well as a general framework for studying UTI-related mechanisms.
    Materialart: Online-Ressource
    ISSN: 1664-3224
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2606827-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-2-17)
    Kurzfassung: Lenvatinib is a first-line treatment for unresectable hepatocellular carcinoma (uHCC). We assessed the value of early alpha-fetoprotein (AFP) response for predicting clinical outcomes with lenvatinib treatment in patients with HBV-related uHCC and elevated AFP levels. Methods This retrospective analysis included patients with HBV-related uHCC and baseline AFP levels ≥20 ng/ml who received lenvatinib for & gt;1 month between November 2018 and May 2021. Early AFP response was defined as a & gt;20% decrease in AFP serum level from baseline after 4 weeks of lenvatinib treatment. Radiological response (Response Evaluation Criteria in Solid Tumors v1.1), progression-free survival, and overall survival were assessed in AFP responders and non-responders. Results Of the 46 patients analyzed, 30 (65.2%) were early AFP responders and 16 (34.8%) were non-responders. Compared to the non-responders, early AFP responders had a significantly higher objective response rate (34.5% vs 6.3%, p=0.0349), disease control rate (82.8% vs 50.0%; p=0.0203) and longer median progression-free survival (13.0 vs 7.0 months; HR, 0.464; 95% CI, 0.222-0.967; p=0.028). A subsequent multivariate analysis confirmed that early AFP response (HR, 0.387; 95% CI, 0.183-0.992; p=0.0154), Eastern Cooperative Oncology Group Performance Status of 0 (HR, 0.890; 95% CI, 0.811-0.976; p=0.0132) and Albumin-Bilirubin grade 1 (HR, 0.457; 95% CI, 0.269-0.963; p=0.0327) were independent prognostic factors for longer progression-free survival. Conclusion AFP is an important prognostic factor and a predictive biomarker for survival benefit with lenvatinib treatment in patients with HBV-related uHCC.
    Materialart: Online-Ressource
    ISSN: 2234-943X
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2649216-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2019
    In:  Frontiers in Neuroscience Vol. 13 ( 2019-5-15)
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 13 ( 2019-5-15)
    Materialart: Online-Ressource
    ISSN: 1662-453X
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2019
    ZDB Id: 2411902-7
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 11 ( 2020-5-5)
    Materialart: Online-Ressource
    ISSN: 1663-9812
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2020
    ZDB Id: 2587355-6
    SSG: 15,3
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2021-11-25)
    Kurzfassung: Background: In recent years, deep learning has been widely used in a variety of ophthalmic diseases. As a common ophthalmic disease, meibomian gland dysfunction (MGD) has a unique phenotype in in-vivo laser confocal microscope imaging (VLCMI). The purpose of our study was to investigate a deep learning algorithm to differentiate and classify obstructive MGD (OMGD), atrophic MGD (AMGD) and normal groups. Methods: In this study, a multi-layer deep convolution neural network (CNN) was trained using VLCMI from OMGD, AMGD and healthy subjects as verified by medical experts. The automatic differential diagnosis of OMGD, AMGD and healthy people was tested by comparing its image-based identification of each group with the medical expert diagnosis. The CNN was trained and validated with 4,985 and 1,663 VLCMI images, respectively. By using established enhancement techniques, 1,663 untrained VLCMI images were tested. Results: In this study, we included 2,766 healthy control VLCMIs, 2,744 from OMGD and 2,801 from AMGD. Of the three models, differential diagnostic accuracy of the DenseNet169 CNN was highest at over 97%. The sensitivity and specificity of the DenseNet169 model for OMGD were 88.8 and 95.4%, respectively; and for AMGD 89.4 and 98.4%, respectively. Conclusion: This study described a deep learning algorithm to automatically check and classify VLCMI images of MGD. By optimizing the algorithm, the classifier model displayed excellent accuracy. With further development, this model may become an effective tool for the differential diagnosis of MGD.
    Materialart: Online-Ressource
    ISSN: 2296-858X
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2021
    ZDB Id: 2775999-4
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    Online-Ressource
    Online-Ressource
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 12 ( 2022-1-17)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2022-1-17)
    Kurzfassung: LAG3 is the most promising immune checkpoint next to PD-1 and CTLA-4. High LAG3 and FGL1 expression boosts tumor growth by inhibiting the immune microenvironment. This review comprises four sections presenting the structure/expression, interaction, biological effects, and clinical application of LAG3/FGL1. D1 and D2 of LAG3 and FD of FGL1 are the LAG3-FGL1 interaction domains. LAG3 accumulates on the surface of lymphocytes in various tumors, but is also found in the cytoplasm in non-small cell lung cancer (NSCLC) cells. FGL1 is found in the cytoplasm in NSCLC cells and on the surface of breast cancer cells. The LAG3-FGL1 interaction mechanism remains unclear, and the intracellular signals require elucidation. LAG3/FGL1 activity is associated with immune cell infiltration, proliferation, and secretion. Cytokine production is enhanced when LAG3/FGL1 are co-expressed with PD-1. IMP321 and relatlimab are promising monoclonal antibodies targeting LAG3 in melanoma. The clinical use of anti-FGL1 antibodies has not been reported. Finally, high FGL1 and LAG3 expression induces EGFR-TKI and gefitinib resistance, and anti-PD-1 therapy resistance, respectively. We present a comprehensive overview of the role of LAG3/FGL1 in cancer, suggesting novel anti-tumor therapy strategies.
    Materialart: Online-Ressource
    ISSN: 1664-3224
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2022
    ZDB Id: 2606827-8
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 8 ( 2017-12-12)
    Materialart: Online-Ressource
    ISSN: 1664-3224
    Sprache: Unbekannt
    Verlag: Frontiers Media SA
    Publikationsdatum: 2017
    ZDB Id: 2606827-8
    Standort Signatur Einschränkungen Verfügbarkeit
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