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  • Frontiers Media SA  (79)
  • 1
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 14 ( 2023-2-15)
    Abstract: Objectives: Dimeric pyruvate kinase (PK) M2 (PKM2) plays an important role in promoting the accumulation of hypoxia-inducible factor (HIF)-1α, mediating aberrant glycolysis and inducing fibrosis in diabetic kidney disease (DKD). The aim of this work was to dissect a novel regulatory mechanism of Yin and Yang 1 (YY1) on lncRNA-ARAP1-AS2/ARAP1 to regulate EGFR/PKM2/HIF-1α pathway and glycolysis in DKD. Materials and methods: We used adeno-associated virus (AAV)-ARAP1 shRNA to knocked down ARAP1 in diabetic mice and overexpressed or knocked down YY1, ARAP1-AS2 and ARAP1 expression in human glomerular mesangial cells. Gene levels were assessed by Western blotting, RT-qPCR, immunofluorescence staining and immunohistochemistry. Molecular interactions were determined by RNA pull-down, co-immunoprecipitation, ubiquitination assay and dual-luciferase reporter analysis. Results: YY1, ARAP1-AS2, ARAP1, HIF-1α, glycolysis and fibrosis genes expressions were upregulated and ARAP1 knockdown could inhibit dimeric PKM2 expression and partly restore tetrameric PKM2 formation, while downregulate HIF-1α accumulation and aberrant glycolysis and fibrosis in in-vivo and in-vitro DKD models. ARAP1 knockdown attenuates renal injury and renal dysfunction in diabetic mice. ARAP1 maintains EGFR overactivation in-vivo and in-vitro DKD models. Mechanistically, YY1 transcriptionally upregulates ARAP1-AS2 and indirectly regulates ARAP1 and subsequently promotes EGFR activation, HIF-1α accumulation and aberrant glycolysis and fibrosis. Conclusion: Our results first highlight the role of the novel regulatory mechanism of YY1 on ARAP1-AS2 and ARAP1 in promoting aberrant glycolysis and fibrosis by EGFR/PKM2/HIF-1α pathway in DKD and provide potential therapeutic strategies for DKD treatments.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 2
    In: Frontiers in Pediatrics, Frontiers Media SA, Vol. 10 ( 2022-8-23)
    Abstract: PhelanrMcDermid syndrome (PMS) is an uncommon autosomal dominant inherited developmental disorder. The main characteristics are hypotonia, intellectual disability, autism spectrum disorder, autism-like behaviors and tiny facial deformities. Most cases are caused by the deletion of the 22q13 genomic region, including the deletion of SHANK3 . Methods Genetic and phenotype evaluations of ten Chinese pediatric patients were performed. The clinical phenotypes and genetic testing results were collected statistically. We analyzed the deletion of the 22q13 genomic region and small mutations in SHANK3 (GRCh37/hg19) and performed parental genotype verification to determine whether it was related to the parents or was a novel mutation. Results The age of the patients diagnosed with PMS ranged from 0 to 12 years old. Nine of the pediatric patients experienced Intellectual Disability, language motion development delay and hypotonia as prominent clinical features. One subject had autism, two subjects had abnormal electroencephalogram discharge and one subject was aborted after fetal diagnosis. Three patients had a SHANK3 mutation or deletion. All but the aborted fetuses had intellectual disability. Among the ten patients, a deletion in the 22q13 region occurred in seven patients, with the smallest being 60.6 kb and the largest being & gt;5.5 Mb. Three patients had heterozygous mutations in the SHANK3 gene. Conclusion All ten patients had novel mutations, and three of these were missense or frameshift mutations. For the first time reported, it is predicted that the amino acid termination code may appear before protein synthesis. The novel mutations we discovered provide a reference for clinical research and the diagnosis of PMS.
    Type of Medium: Online Resource
    ISSN: 2296-2360
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2711999-3
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-6-29)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-6-29)
    Abstract: Macrophage migration inhibitory factor (MIF) has been shown to promote disease progression in many malignancies, including multiple myeloma (MM). We previously reported that MIF regulates MM bone marrow homing and knockdown of MIF favors the extramedullary myeloma formation in mice. Here, based on MIF immunostaining of myeloma cells in paired intramedullary and extramedullary biopsies from 17 patients, we found lower MIF intensity in extramedullary MM (EMM) versus intramedullary MM (IMM). Flow cytometry and histology analysis in xenograft models showed a portion of inoculated human MM cells lost their MIF expression (MIF Low ) in vivo . Of note, IMM had dominantly MIF High cells, while EMM showed a significantly increased ratio of MIF Low cells. Furthermore, we harvested the extramedullary human MM cells from a mouse and generated single-cell transcriptomic data. The developmental trajectories of MM cells from the MIF High to MIF Low state were indicated. The MIF High cells featured higher proliferation. The MIF Low ones were more quiescent and harbored abundant ribosomal protein genes. Our findings identified in vivo differential regulation of MIF expression in MM and suggested a potential pathogenic role of MIF in the extramedullary spread of disease.
    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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  • 4
    In: Frontiers in Public Health, Frontiers Media SA, Vol. 9 ( 2022-1-5)
    Abstract: Background: The shortage of primary medical staff is a major problem in the management of health human resources across many developing countries. By determining their preferences for various motivational and related factors, we examined the correlation between staff's motivation preference levels and staff turnover and turnover intention. This study aimed to further improve the incentive mechanism and to provide a reference for healthcare managers to formulate management strategies for the primary medical staff team. Methods: A self-reported questionnaire survey was conducted to collect data. The basic survey content included demographic characteristics. The absolute level questionnaire and relative level questionnaire on the factors affecting motivation preference were used as the main assessment scales. A total of 1,112 primary health workers in Anhui Province were investigated. T -test, analysis of variance (ANOVA), exploratory factor analysis, and multiple linear regression analysis were performed to analyze the data. Results: The survey respondents (45.1%) reported being satisfied with their relationship with colleagues, and other social relationships (46.9%). The Kaiser Meyer Olkin (KMO) value for the absolute preference degree for motivational factors was 0.951. Two factors (economic and non-economic factors), after using the maximum variance rotation axis method, explained 81.25% of the total variance. The regression analysis showed that primary medical staff members with low monthly income ( B = −0.157) have a higher preference for non-economic factors; the higher the educational background ( B = 0.133), the higher their preference for economic factors. In addition, with the increase in participants' age ( B = −0.250), the preference for motivational factors gradually decreased. Conclusion: Both economic and non-economic factors play an important role in enhancing the enthusiasm of primary medical workers and improving their work attitude. Managers should use their influence to stabilize the primary medical staff.
    Type of Medium: Online Resource
    ISSN: 2296-2565
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2711781-9
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Plant Science Vol. 13 ( 2022-7-12)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 13 ( 2022-7-12)
    Abstract: Reactive oxygen species (ROS) play important regulatory roles in plant growth and development, as well as in cell differentiation and stress responses. Respiratory burst oxidase homolog (RBOH) is the key enzyme in ROS production. So far, the Rboh family genes in Pyropia yezoensis have not been comprehensively characterized, and whether their function was involved in the formation of archeospores is still unknown. In this study, a total of 11 PyRboh genes were identified from the P. yezoensis genome by homology mining. Through phylogenetic analysis, it is suggested that the PyRboh genes were evolutionarily conserved among the lineages of red algae, but a few genes exhibited a species-specific manner. The treatment of P. yezoensis blades with NADPH oxidase inhibitor diphenylene iodonium (DPI) could significantly inhibit the formation of archeospores, suggesting that RBOH may be involved in the formation of archeospores. According to PyRboh gene expression analysis using the P. yezoensis strains with obvious differences in releasing archeospores, it is showed that the expression trends of most genes were consistent, with no significant difference between strains, whereas the expression pattern of the two P. yezoensis -specific genes ( PyRbohJ and PyRbohK ) was positively correlated with the amount of archeospores. Furthermore, as treatment of blades with allantoin resulted in a significant increase in the release of archeospores, the expression levels of PyRbohJ and PyRbohK were also consistently upregulated, further confirming the relationship between the two genes and archeospore formation. These findings provide insights into the molecular mechanism of P. yezoensis archeospore formation.
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2613694-6
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Nutrition Vol. 10 ( 2023-9-14)
    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 10 ( 2023-9-14)
    Abstract: Although numerous epidemiological studies investigated the association between dietary fat intakes or serum lipid levels and ovarian cancer risk, a consistent and explicit conclusion for specific dietary fats or serum lipids that increase the risk of ovarian cancer is not available. In this study, a systematic review and meta-analysis were conducted to assess the key dietary fats and serum lipids that increased the risk of ovarian cancer. Databases such as PubMed, Web of Science, and EMBASE were searched for observational studies. A total of 41 studies met the inclusion criteria, including 18 cohort and 23 case–control studies (109,507 patients with ovarian cancer and 2,558,182 control/non-ovarian cancer participants). Higher dietary intakes of total fat (RR = 1.19, 95% CI = 1.06–1.33, I 2 = 60.3%), cholesterol (RR = 1.14, 95% CI = 1.03–1.26, I 2 = 19.4%), saturated fat (RR = 1.13, 95% CI = 1.04–1.22, I 2 = 13.4%), and animal fat (RR = 1.21, 95% CI = 1.01–1.43, I 2 = 70.5%) were significantly associated with a higher risk of ovarian cancer. A higher level of serum triglycerides was accompanied by a higher risk of ovarian cancer (RR = 1.33, 95% CI = 1.02–1.72, I 2 = 89.3%). This meta-analysis indicated that a higher daily intake of total fat, saturated fat, animal fat, and cholesterol and higher levels of serum triglycerides were significantly associated with an increased risk of ovarian cancer.
    Type of Medium: Online Resource
    ISSN: 2296-861X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2776676-7
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Neuroscience Vol. 16 ( 2022-5-9)
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 16 ( 2022-5-9)
    Abstract: It has been established that the dipeptidyl peptidase-4 (DPP-4) inhibitor Diprotin A TFA can reduce vascular endothelial (VE)-cadherin disruption by inhibiting the increase in cleaved β-catenin in response to hypoxia, thereby protecting the vascular barrier of human umbilical vein endothelial cells. In this study, we sought to investigate the possible effect of Diprotin A TFA on the VE barrier after cerebral ischemic stroke in mice. Methods C57BL/6J mice were divided into five groups, namely, (1) sham, (2) stroke, (3) stroke + dimethyl sulfoxide (DMSO), (4) stroke + Diprotin A TFA, and (5) stroke + Diprotin A TFA + XAV-939. First, the cerebral ischemia model was established by photothrombotic ischemia, followed by intraperitoneal injection with Diprotin A TFA and XAV-939 at doses of 70 μg/kg and 40 mg/kg 30 min once in the morning and once in the evening for 3 days. Immunofluorescence staining and Western blot methods were used to analyze the expression of vascular and blood-brain barrier (BBB)-associated molecular markers in the peri-infarct area. Results Compared with the vehicle control group, we found that mice injected with Diprotin A TFA exhibited reduced cerebral infarction volume, increased vascular area and length around the brain injury, increased pericyte and basement membrane coverage, upregulated expression of BBB tight junction proteins, and improved their BBB permeability, whereas the group injected with both drug and inhibitor exhibited significantly aggravated vascular injury and BBB permeability. Conclusion Diprotin A TFA can reduce VE-cadherin disruption by inhibiting ischemia-hypoxia-induced β-catenin cleavage to protect blood vessels.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2411902-7
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  • 8
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-3-24)
    Abstract: Yersinia pestis , the cause of plague, is a newly evolved Gram-negative bacterium. Through the acquisition of the plasminogen activator (Pla), Y. pestis gained the means to rapidly disseminate throughout its mammalian hosts. It was suggested that Y. pestis utilizes Pla to interact with the DEC-205 (CD205) receptor on antigen-presenting cells (APCs) to initiate host dissemination and infection. However, the evolutionary origin of Pla has not been fully elucidated. The PgtE enzyme of Salmonella enterica , involved in host dissemination, shows sequence similarity with the Y. pestis Pla. In this study, we demonstrated that both Escherichia coli K-12 and Y. pestis bacteria expressing the PgtE-protein were able to interact with primary alveolar macrophages and DEC-205-transfected CHO cells. The interaction between PgtE-expressing bacteria and DEC-205-expressing transfectants could be inhibited by the application of an anti-DEC-205 antibody. Moreover, PgtE-expressing Y. pestis partially re-gained the ability to promote host dissemination and infection. In conclusion, the DEC-205-PgtE interaction plays a role in promoting the dissemination and infection of Y. pestis , suggesting that Pla and the PgtE of S. enterica might share a common evolutionary origin.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 9
    In: Frontiers in Psychiatry, Frontiers Media SA, Vol. 13 ( 2022-10-24)
    Abstract: Depression often triggers addictive behaviors such as Internet addiction. In this network analysis study, we assessed the association between Internet addiction and residual depressive symptoms in patients suffering from clinically stable recurrent depressive disorder (depression hereafter). Materials and methods In total, 1,267 depressed patients were included. Internet addiction and residual depressive symptoms were measured using the Internet Addiction Test (IAT) and the two-item Patient Health Questionnaire (PHQ-2), respectively. Central symptoms and bridge symptoms were identified via centrality indices. Network stability was examined using the case-dropping procedure. Results The prevalence of IA within this sample was 27.2% (95% CI: 24.7–29.6%) based on the IAT cutoff of 50. IAT15 (“Preoccupation with the Internet”), IAT13 (“Snap or act annoyed if bothered without being online”) and IAT2 (“Neglect chores to spend more time online”) were the most central nodes in the network model. Additionally, bridge symptoms included the node PHQ1 (“Anhedonia”), followed by PHQ2 (“Sad mood”) and IAT3 (“Prefer the excitement online to the time with others”). There was no gender difference in the network structure. Conclusion Both key central and bridge symptoms found in the network analysis could be potentially targeted in prevention and treatment for depressed patients with comorbid Internet addiction and residual depressive symptoms.
    Type of Medium: Online Resource
    ISSN: 1664-0640
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564218-2
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2019
    In:  Frontiers in Pharmacology Vol. 9 ( 2019-1-9)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 9 ( 2019-1-9)
    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
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