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  • Frontiers Media SA  (411)
  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-10-4)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-10-4)
    Abstract: Presently, a comprehensive analysis of integrin subunit genes (ITGs) in bladder cancer (BLCA) is absent. This study endeavored to thoroughly analyze the utility of ITGs in BLCA through computer algorithm-based bioinformatics. Methods BLCA-related materials were sourced from reputable databases, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). R software-based bioinformatics analyses included limma-differential expression analysis, survival-Cox analysis, glmnet-Least absolute shrinkage and selection operator (LASSO), clusterProfiler-functional annotation, and gsva-estimate-immune landscape analysis. The expression difference of key genes was verified by quantitative real-time polymerase chain reaction (qRT-PCR). Results Among the 11 ITGs that were abnormally expressed in BLCA, ITGA7, ITGA5, and ITGB6 were categorized as the optimal variables for structuring the risk model. The high-risk subcategories were typified by brief survival, abysmal prognosis, prominent immune and stromal markers, and depressed tumor purity. The risk model was also an isolated indicator of the impact of clinical outcomes in BLCA patients. Moreover, the risk model, specifically the high-risk subcategory with inferior prognosis, became heavily interlinked with the immune-inflammatory response and smooth muscle contraction and relaxation. Conclusion This study determined three ITGs with prognostic values (ITGA7, ITGA5, and ITGB6), composed a novel (ITG-associated) prognostic gene signature, and preliminarily probed the latent molecular mechanisms of the model.
    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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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Cell and Developmental Biology Vol. 9 ( 2021-10-14)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 9 ( 2021-10-14)
    Abstract: In radiation oncology, ionizing radiation is used to kill cancer cells, in other words, the induction of different types of cell death. To investigate this cellular death and the associated iron accumulation, the transfer, release, and participation of iron after radiation treatment was analyzed. We found that radiation-induced cell death varied in different breast cancer cells and autophagy was induced in MDA-MB-231 and BT549 cells (triple negative breast cancer cell line) rather than in MCF-7 and zr-75 cells. Iron chelator deferoxamine (DFO), the autophagy inhibitor 3MA, silencing of the autophagy-related genes ATG5, and Beclin 1 could decrease radiation induced cell death in MDA-MB-231 cells, while inhibitors of apoptosis such as Z-VAD-FMK, ferroptosis inhibitor ferrostatin-1 (Fer-1), and necroptosis inhibitor Necrostatin-1 showed no change. This suggests the occurrence of autophagic cell death. Furthermore, we found that iron accumulation and iron regulatory proteins, including transferrin (Tf), transferrin receptor (CD71), and Ferritin (FTH), increased after radiation treatment, and the silencing of transferrin decreased radiation-induced cell death. In addition, radiation increased lysosomal membrane permeabilization (LMP) and the release of lysosomal iron and cathepsins, while cathepsins silencing failed to change cell viability. Radiation-induced iron accumulation increased Reactive oxygen species (ROS) generation via the Fenton reaction and increased autophagy in a time-dependent manner. DFO, N -acetylcysteine (NAC), and overexpression of superoxide dismutase 2 (SOD2) decreased ROS generation, autophagy, and cell death. To summarize, for the first time, we found that radiation-induced autophagic cell death was iron-dependent in breast cancer MDA-MB-231 cells. These results provide new insights into the cell death process of cancers and might conduce to the development and application of novel therapeutic strategies for patients with apoptosis-resistant breast cancer.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2737824-X
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Plant Science Vol. 13 ( 2022-5-25)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 13 ( 2022-5-25)
    Abstract: Salt stress is one of the most devastating environmental factors threatening soybean growth and yield. However, the molecular link between salt stress and epigenetics has not been well-elucidated in soybean. In this study, from the wild soybean cDNA library, we isolated a GsSnRK1 kinase interacting protein (GsMSTY1) which is phylogenetically homologous with histone acetyltransferase MYST family with unknown function. GsMSTY1 gene is dominantly expressed in wild soybean roots and is highly responsive to abiotic stresses. GsMYST1 was able to be phosphorylated at the Ser44 site by GsSnRK1 and demonstrated in vivo acetyltransferase activity in transgenic soybean roots revealed by an anti-H4ace antibody. A transcription factor protein GsNAC83 was identified to interact with both GsMYST1 and GsSnRK1, and GsNAC83 could recruit the GsMYST1-GsSnRK1 module to COR15B gene promoter determined by ChIP-qPCR assay. To dissect the molecular functions of this ternary complex, we treated the transgenic soybean roots with salt stress and found that the stress could activate GsSnRK1, and the activated GsSnRK1 subsequently phosphorylated GsMYST1 to enhance its acetyltransferase activity which may epigenetically promote the target gene expression. To explore the physiological functions, we coexpressed GsSnRK1 and GsMYST1 genes in soybean hairy roots and found that only GsSnRK1 (wt)/ GsMYST1 (wt) but not the mutant genes could promote soybean resistance to salt stress, implicating that phosphorylation of GsMYST1 is required for it to acetylate histone H4 on the target genes to upregulate expression of the stress-related genes. Our data shed new light on the functions of the GsSnRK1-GsMYST1-GsNAC83 module and its regulatory mechanism on plant tolerance to abiotic stresses.
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-10-13)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-10-13)
    Abstract: Aim: Hepatic ischemia-reperfusion (HIR) induces remote organs injury, including the brain. The homeostasis of the brain is maintained by the blood-brain barrier (BBB); thus, we aimed to investigate whether HIR impaired BBB and attempted to elucidate its underlying mechanism. Methods: Cell viability of human cerebral microvascular endothelial cells (hCMEC/D3) was measured following 24 h incubation with a serum of HIR rat undergoing 1 h ischemia and 4 h reperfusion, liver homogenate, or lysate of primary hepatocytes of the rat. The liver homogenate was precipitated using (NH 4 ) 2 SO 4 followed by separation on three columns and electrophoresis to identify the toxic molecule. Cell activity, apoptosis, proliferation, cell cycle, and expressions of proteins related to cell cycle were measured in hCMEC/D3 cells incubated with identified toxic molecules. HIR rats undergoing 1 h ischemia and 24 h reperfusion were developed to determine the release of an identified toxic molecule. BBB function was indexed as permeability to fluorescein and brain water. Endothelial cell proliferation and expressions of proteins related to the cell cycle in cerebral microvessels were measured by immunofluorescence and western blot. Results: Toxic molecule to BBB in the liver was identified to be arginase. Arginase inhibitor nor-NOHA efficiently attenuated hCMEC/D3 damage caused by liver homogenate and serum of HIR rats. Both arginase and serum of HIR rats significantly lowered arginine (Arg) in the culture medium. Arg addition efficiently attenuated the impairment of hCMEC/D3 caused by arginase or Arg deficiency, demonstrating that arginase impaired hCMEC/D3 via depriving Arg. Both arginase and Arg deficiency damaged hCMEC/D3 cells by inhibiting cell proliferation, retarding the cell cycle to G1 phase, and downregulating expressions of cyclin A, cyclin D, CDK2, and CDK4. HIR notably increased plasma arginase activity and lowered Arg level, increased the BBB permeability accompanied with enhanced brain water, and decreased the proliferative cells (marked by Ki67) in cerebral microvessels (marked by CD31) and protein expressions of cyclin A, cyclin D, CDK2 and CDK4 in isolated brain microvessels. Oral supplement of Arg remarkably attenuated these HIR-induced alterations. Conclusion: HIR leads to substantial release of arginase from the injured liver and then deprives systemic Arg. The Arg deficiency further impairs BBB via inhibiting the proliferation of brain microvascular endothelial cells by cell cycle arrest.
    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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  • 5
    In: Frontiers in Psychology, Frontiers Media SA, Vol. 13 ( 2022-6-10)
    Abstract: Turnover intention, an employee’s intention to voluntarily leave their jobs, affects workforce sustainability. However, scarce data are available about turnover intention and its associated factors among psychiatrists in China, especially during the COVID-19 pandemic. The current research was designed to address this gap. Methods An anonymous, nationwide online survey was disseminated to psychiatrists in 41 psychiatric hospitals in China. We collected demographic data, job-related information (duration of employment, history of participation in the frontline work against COVID-19, job satisfaction), and participants’ turnover intention in the next 12 months. Results In total, 3,973 psychiatrists completed the survey. The sample was predominantly female (58.8%) and married (79.5%), and nearly three-fourths (73.5%) had children. More than one-third (35.6%) had a master’s or doctoral degree in addition to their medical degree. The overall level of job satisfaction was moderate. The rate of turnover intention was 22.0% and was comparable in males and females (22.9% in males and 21.3% in females, respectively). Psychiatrists who had participated in the frontline work of COVID-19 were more likely to report an intention to leave their current job. Multiple regression analyses suggested that turnover intention was significantly associated with having insomnia, longer working hours, and more working days per week. Conclusion During the pandemic period, approximately one-fifth of psychiatrists in China reported turnover intention. Factors associated with turnover intention included high job-related burdens, low job satisfaction, participation in the frontline work against COVID-19, and insomnia. To improve psychiatric workforce sustainability, policymakers and hospital administrators need to be aware of this potential challenge and address the concerns of psychiatrists in China.
    Type of Medium: Online Resource
    ISSN: 1664-1078
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2563826-9
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cell and Developmental Biology Vol. 9 ( 2022-2-16)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 9 ( 2022-2-16)
    Abstract: Radiotherapy is one of the most important treatments for breast cancer. Ferroptosis is a recently recognized form of regulated cell death that is characterized by lipid peroxidation. However, whether ionizing radiation (IR) could induce ferroptosis in breast cancer and how it works remain unknown. Bioinformatics analysis were performed to screen ferroptosis-related genes differentially expressed in breast tumor tissue and normal tissue. Then, breast cancer cell lines with different estrogen receptor (ER) phenotypes were used for studies in vitro , including ER-positive (MCF-7 and ZR-75-1) and ER-negative (MDA-MB-231) cells. The dynamic changes of mRNA and protein levels were examined after x-ray of 8 Gy by qRT-PCR and Western blotting, respectively. Immunoprecipitation (IP) was used to explore the interaction between proteins. Luciferase assay was used to analyze the transcriptional regulation effect of ESR1 on SLC7A11. BODIPY C11 and trypan blue dyes were used to determine lipid peroxidation and cell death, respectively. The result showed that the ferroptosis-related gene SLC7A11 was higher in breast cancer tissues compared with normal tissues and associated with poor survival. A positive correlation exists between ESR1 and SLC7A11 expression. ESR1 promoted SLC7A11 expression at the early stage after IR. ESR1/SLC7A11 knockdown significantly enhanced IR-induced ferroptosis in ER-positive cells. At 12 h after IR, the IP data showed the interaction between E3 ubiquitin ligase NEDD4L and SLC7A11 increased, followed by the ubiquitylation and degradation of SLC7A11. Thus, SLC7A11 expression was regulated by both ESR1 and NEDD4L, in opposite ways. For the first time, we elucidated that ESR1 and NEDD4L functioned together after radiation treatment and finally induced ferroptosis in breast cancer cells, which provides novel insight into the guidance of clinical treatment of breast cancer.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2737824-X
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-6-9)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-6-9)
    Abstract: AI-based clinical decision support system (CDSS) has important prospects in overcoming the current informational challenges that cancer diseases faced, promoting the homogeneous development of standardized treatment among different geographical regions, and reforming the medical model. However, there are still a lack of relevant indicators to comprehensively assess its decision-making quality and clinical impact, which greatly limits the development of its clinical research and clinical application. This study aims to develop and application an assessment system that can comprehensively assess the decision-making quality and clinical impacts of physicians and CDSS. Methods Enrolled adjuvant treatment decision stage early breast cancer cases were randomly assigned to different decision-making physician panels (each panel consisted of three different seniority physicians in different grades hospitals), each physician made an independent “Initial Decision” and then reviewed the CDSS report online and made a “Final Decision”. In addition, the CDSS and guideline expert groups independently review all cases and generate “CDSS Recommendations” and “Guideline Recommendations” respectively. Based on the design framework, a multi-level multi-indicator system including “Decision Concordance”, “Calibrated Concordance”, “ Decision Concordance with High-level Physician”, “Consensus Rate”, “Decision Stability”, “Guideline Conformity”, and “Calibrated Conformity” were constructed. Results 531 cases containing 2124 decision points were enrolled; 27 different seniority physicians from 10 different grades hospitals have generated 6372 decision opinions before and after referring to the “CDSS Recommendations” report respectively. Overall, the calibrated decision concordance was significantly higher for CDSS and provincial-senior physicians (80.9%) than other physicians. At the same time, CDSS has a higher “ decision concordance with high-level physician” (76.3%-91.5%) than all physicians. The CDSS had significantly higher guideline conformity than all decision-making physicians and less internal variation, with an overall guideline conformity variance of 17.5% (97.5% vs. 80.0%), a standard deviation variance of 6.6% (1.3% vs. 7.9%), and a mean difference variance of 7.8% (1.5% vs. 9.3%). In addition, provincial-middle seniority physicians had the highest decision stability (54.5%). The overall consensus rate among physicians was 64.2%. Conclusions There are significant internal variation in the standardization treatment level of different seniority physicians in different geographical regions in the adjuvant treatment of early breast cancer. CDSS has a higher standardization treatment level than all physicians and has the potential to provide immediate decision support to physicians and have a positive impact on standardizing physicians’ treatment behaviors.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 8
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 7 ( 2016-12-16)
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2016
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2019
    In:  Frontiers in Integrative Neuroscience Vol. 13 ( 2019-10-16)
    In: Frontiers in Integrative Neuroscience, Frontiers Media SA, Vol. 13 ( 2019-10-16)
    Type of Medium: Online Resource
    ISSN: 1662-5145
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2452962-X
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  • 10
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-9-16)
    Abstract: The treatment of complex cerebrovascular diseases (CCVDs) at the skull base, such as complex intracranial aneurysms, carotid-cavernous sinus fistulas, and intracranial artery traumatic injuries, is a difficult clinical problem despite advances in endovascular and surgical therapies. Covered stents or stent graft insertion is a new concept for endovascular treatment that focuses on arterial wall defect reconstruction, differing from endovascular lesion embolization or flow diverter therapies. In recent years, covered stents specifically designed for cerebrovascular treatment have been applied in the clinical setting, allowing thousands of patients with CCVDs to undergo intraluminal reconstruction treatment and achieving positive results, even in the era of flow diverters. Since there is no unified reference standard for the application of covered stents for treating CCVDs, it is necessary to further standardize and guide the clinical application of this technique. Thus, we organized authoritative experts in the field of neurointervention in China to write an expert consensus, which aims to summarize the results of covered stent insertion in the treatment of CCVDs and propose suitable standards for its application in the clinical setting. Based on the contents of this consensus, clinicians can use individualized intraluminal reconstruction treatment techniques for patients with CCVDs.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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