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  • Frontiers Media SA  (271)
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  • Frontiers Media SA  (271)
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  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-3-9)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-3-9)
    Abstract: As an important early source of IL-17A and IL-22 in immune responses, type 3 innate lymphoid cells (ILC3s) are critically regulated by the transcription factor retinoic-acid-receptor-related orphan receptor gamma t (RORγt). Previously, we have identified a crucial role of the conserved non-coding sequence 9 (CNS9), located at +5,802 to +7,963 bp of the Rorc gene, in directing T helper 17 differentiation and related autoimmune disease. However, whether cis -acting elements regulate RORγt expression in ILC3s is unknown. Results Here we show that CNS9 deficiency in mice not only decreases ILC3 signature gene expression and increases ILC1-gene expression features in total ILC3s, but also leads to generation of a distinct CD4 + NKp46 + ILC3 population, though the overall numbers and frequencies of RORγt + ILC3s are not affected. Mechanistically, CNS9 deficiency selectively decreases RORγt expression in ILC3s, which thus alters ILC3 gene expression features and promotes cell-intrinsic generation of CD4 + NKp46 + ILC3 subset. Conclusion Our study thus identifies CNS9 as an essential cis -regulatory element controlling the lineage stability and plasticity of ILC3s through modulating expression levels of RORγt protein.
    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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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cell and Developmental Biology Vol. 10 ( 2022-5-12)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 10 ( 2022-5-12)
    Abstract: Metabotropic glutamate receptor subtype 5 (mGluR5) is a G-protein-coupled receptor found widely in the central nervous system. It has been involved in the development and progression of some neurodegenerative diseases, but its role in prion diseases is rarely described. In this study, the changes of mGluR5 and its downstream signaling pathways in prion-infected cell line SMB-S15 and the brains of scrapie-infected experimental rodents were evaluated by various methodologies. We found the levels of mGluR5 were significantly increased in a prion-infected cell line SMB-S15 and the cultured cells transiently express an abnormal form PrP (Cyto-PrP). Using immunoprecipitation tests and immunofluorescent assays (IFA), molecular interaction and morphological colocalization between PrP and mGluR5 were observed in the cultured cells. We identified that the (GPCRs)-IP3-IP3R-Ca 2+ pathway was activated and the levels of the downstream kinases p38, ERK, and JNK were increased in SMB-S15 cells. After treated with mGluR5 antagonist (MTEP) or the removal of prion replication by resveratrol in SMB-S15 cells, the upregulations of mGluR5 and the downstream kinases were restored in a certain degree. Moreover, increased mGluR5 contributes to the cell damage in prion-infected cells. Contrarily, the levels of mGluR5 in the brains of several scrapie-infected rodent models were decreased at terminal stage. IFA of the brain sections of scrapie-infected rodents demonstrated that the signals of mGluR5 were preferentially colocalized with the NeuN-positive cells, accompanying with severe neuron losses in Nissl staining, which might be a reason for the decrease of mGluR5. Our data indicate the different aberrant alterations of mGluR5 and the downstream signaling pathways during prion infection in vivo and in vitro .
    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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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Medicine Vol. 8 ( 2021-9-16)
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2021-9-16)
    Abstract: Background: Previous research suggested that Chinese Medicine (CM) Formula Huashibaidu granule might shorten the disease course in coronavirus disease 2019 (COVID-19) patients. This research aimed to investigate the early treatment effect of Huashibaidu granule in well-managed patients with mild COVID-19. Methods: An unblinded cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. Two cabins were randomly allocated to a CM or control group, with 204 mild COVID-19 participants in each cabin. All participants received conventional treatment over a 7 day period, while the ones in CM group were additionally given Huashibaidu granule 10 g twice daily. Participants were followed up to their clinical endpoint. The primary outcome was worsening symptoms before the clinical endpoint. The secondary outcomes were cure and discharge before the clinical endpoint and alleviation of composite symptoms after the 7 days of treatment. Results: All 408 participants were followed up to their clinical endpoint and included in statistical analysis. Baseline characteristics were comparable between the two groups ( P & gt; 0.05). The number of worsening patients in the CM group was 5 (2.5%), and that in the control group was 16 (7.8%) with a significant difference between groups ( P = 0.014). Eight foreseeable mild adverse events occurred without statistical difference between groups ( P = 0.151). Conclusion: Seven days of early treatment with Huashibaidu granule reduced the likelihood of worsening symptoms in patients with mild COVID-19. Our study supports Huashibaidu granule as an active option for early treatment of mild COVID-19 in similar well-managed medical environments. Clinical Trial Registration: www.chictr.org.cn/showproj.aspx?proj=49408 , identifier: ChiCTR2000029763.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2775999-4
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  • 4
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-7-15)
    Abstract: Patients with early-stage laryngeal cancer, even stage T1-2N0, are at considerable risk of recurrence and death. The genetic and immunologic characteristics of recurrent laryngeal cancer remain unclear. Methods A total of 52 T1-2N0 laryngeal cancer patients were enrolled. Of these, 42 tissue samples were performed by targeted DNA sequencing, and 21 cases were performed by NanoString immuno-oncology targeted RNA sequencing to identify the distinct molecular bases and immunologic features associated with relapse in patients with early laryngeal cancer, respectively. Results To the best to our knowledge, we present for the first time an overview of the genomic mutation spectrum of early-stage laryngeal cancers. A total of 469 genomic alterations were detected in 211 distinct cancer-relevant genes, and the genes found to be mutated in more than five patients ( & gt;10%) included tumor protein p53 ( TP53 , 78.5%), FAT atypical cadherin 1 ( FAT1 , 26%), LDL receptor related protein 1B ( LRP1B , 19%), cyclin dependent kinase inhibitor 2A ( CDKN2A , 17%), tet methylcytosine dioxygenase 2 ( TET2 , 17%), notch receptor 1 ( NOTCH1 , 12%) and neuregulin 1 ( NRG1 , 12%). Recurrent laryngeal cancer demonstrated a higher tumor mutation burden (TMB), as well as higher LRP1B mutation and NOTCH1 mutation rates. Univariate and multivariate analyses revealed that high TMB (TMB-H) and NOTCH1 mutation are independent genetic factors that are significantly associated with shorter relapse-free survival (RFS). Simultaneously, the results of the transcriptome analysis presented recurrent tumors with NOTCH1 mutation displayed upregulation of the cell cycle pathway, along with decreased B cells score, T cells score, immune signature score and tumor-infiltrating lymphocytes (TILs) score. The Cancer Genome Atlas (TCGA)-laryngeal cancer dataset also revealed weakened immune response and impaired adhesion functions in NOTCH1 -mutant patients. Conclusions Genomic instability and impaired immune response are key features of the immunosurveillance escape and recurrence of early laryngeal cancer after surgery. These findings revealed immunophenotypic attenuation in recurrent tumors and provided valuable information for improving the management of these high-risk patients. Due to the small number of patients in this study, these differences need to be further validated in a larger cohort.
    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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  • 5
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 14 ( 2022-7-1)
    Abstract: The real-time quaking-induced conversion (RT-QuIC) assay has been developed and used as an in vitro diagnostic tool for Parkinson’s disease (PD). In this study, we established α-Syn RT-QuIC using recombinant human α-Syn as the substrate. All 5 brain homogenates of neuropathological PD cases and 13 skin homogenates of clinical PD cases showed positive results, whereas all the samples of negative controls remain negative. Meantime, randomly selected 6 skin samples of PD cases and 6 skin samples of sCJD cases showed negative in opposite prion RT-QuIC and α-Syn RT-QuIC. Our α-Syn RT-QuIC showed dose-dependent manner between the lag times and peak ThT fluorescent values. Additionally, the detecting limitation was about 10 –7 dilution for brain tissues and 10 –6 for skins. Those data indicate a reliable specificity and good sensitivity of the established α-Syn RT-QuIC in identifying and amplifying the misfolded α-Syn in brain and skin tissues of patients with PD.
    Type of Medium: Online Resource
    ISSN: 1663-4365
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2558898-9
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Nutrition Vol. 8 ( 2021-5-13)
    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 8 ( 2021-5-13)
    Abstract: Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Folate has been demonstrated to be associated with ASD. However, current studies on the correlation between folate and symptoms of children with ASD have inconsistent conclusions, use mainly small samples, and lack age-stratified analysis. This study aimed to explore the association between serum folate and symptoms of autistic children at different age groups from a multi-center perspective. Methods: We enrolled 1,300 children with ASD and 1,246 typically developing (TD) children under 7 years old from 13 cities in China. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood autism rating scale (CARS) were used to evaluate the symptoms of children with ASD. China neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) scale was used to evaluate the neurodevelopment of children with ASD. Serum folate was measured by chemiluminescence assay in the two groups. Results: The serum folate levels of children with ASD were lower than that of TD children. In terms of core symptoms of ASD, we found that the serum folate levels were not associated with ABC, SRS, and CARS scores in ASD children of all ages but negatively associated with communication warning behavior scores of CNBS-R2016 in ASD children aged three and under. Concerning development quotients, it was at the age of three and under that serum folate levels were positively associated with gross motor, fine motor, language, and general quotient of ASD children. These ASD children aged three and under were further divided into two groups according to the median of serum folate (14.33 ng/mL); we found that compared to ASD children with folate ≤ 14.33 ng/mL, those with folate & gt;14.33 ng/mL had lower communication warning behavior score and higher gross motor, fine motor, adaptive behavior, language, person-social, and general development quotients. Conclusion: We found that serum folate status was primarily associated with the neurodevelopment of children with ASD aged three and under. Furthermore, relatively higher serum folate levels may be more beneficial for children with ASD. Our results suggest that folate level should be paid more attention in ASD children, especially in early life, to better promote the intervention of ASD children.
    Type of Medium: Online Resource
    ISSN: 2296-861X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2776676-7
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Oncology Vol. 10 ( 2020-9-15)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 10 ( 2020-9-15)
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2649216-7
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Cardiovascular Medicine Vol. 8 ( 2021-11-18)
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 8 ( 2021-11-18)
    Abstract: Background: Hypertension is a leading contributor to the global burden of disease and to mortality. The combined effects of sleep factors on the risk of hypertension are unclear. We aimed to evaluate the effect of combined sleep factors on the risk of hypertension and to explore whether this association is independent of genetic risk. Methods: This population-based prospective cohort study included 170,378 participants from the UK Biobank study. We conducted a healthy sleep score based on a combination of major five sleep factors and a genetic risk score based on 118 risk variants. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: A total of 170,378 participants were included. Compared to participants with a healthy sleep score of 0–1, those with healthy sleep scores of 2 (HR, 0.90; 95% CI, 0.83–0.98), 3 (HR, 0.81; 95% CI, 0.75–0.88), 4 (HR, 0.74; 95% CI, 0.68–0.81), or 5 (HR, 0.67; 95% CI, 0.59–0.77) had increasingly lower risks of hypertension ( P for trend & lt;0.001). Participants with high genetic risk and an unfavorable sleep pattern had a 1.80-fold greater risk of hypertension than participants with low genetic risk and a favorable sleep pattern. The association between sleep patterns and hypertension persisted in subgroup analysis, stratified by the genetic risk. Nearly 18.2% of hypertension events in this cohort could be attributed to unfavorable sleep pattern. Conclusions: Favorable sleep pattern was associated with a low risk of hypertension, regardless of genetic risk. These findings highlight the potential of sleep interventions to reduce risk of hypertension across entire populations.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2781496-8
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  • 9
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 14 ( 2022-8-22)
    Abstract: Matrix metalloproteinases (MMPs) are essential for tissue formation, neuronal network remodeling, and blood–brain barrier integrity. MMPs have been widely studied in acute brain diseases. However, the relationship with Parkinson’s disease (PD) remains unclear. The purpose of this study was to evaluate the serum MMP3 and MMP9 levels of PD patients and analyze their correlation with non-motor symptoms. Methods In this cross-sectional study, we recruited 73 patients with idiopathic PD and 64 healthy volunteers. Serum MMP3 and MMP9 levels were measured by enzyme-linked immunosorbent assay (ELISA). Patients with PD were assessed for non-motor symptoms using the Non-motor Symptoms Scale (NMSS) and Parkinson’s disease sleep scale (PDSS) and Mini Mental State Examination (MMSE). Results Serum MMP3 levels were significantly decreased in PD patients, predominantly those with early-stage PD, compared with controls [12.56 (9.30, 17.44) vs. 15.37 (11.33, 24.41) ng/ml; P = 0.004], and the serum MMP9 levels of PD patients were significantly higher than those of healthy controls [522 (419, 729) vs. 329 (229, 473) ng/ml; P & lt; 0.001]. MMP3 levels were positively correlated with the NMSS total score ( r = 0.271, P = 0.020) and the single-item scores for item six, assessing the gastrointestinal tract ( r = 0.333, P = 0.004), and there was an inverse correlation between serum MMP3 levels and PDSS score ( r = –0.246, P = 0.036); meanwhile, MMP9 levels were positively correlated with the NMSS total score ( r = 0.234, P = 0.047), and higher serum MMP9 levels were detected in the cognitive dysfunction subgroup than in the cognitively intact subgroup [658 (504, 877) vs. 502 (397, 608) ng/ml, P = 0.008]. Conclusion The serum MMP3 level of PD patients (especially early-stage patients) was significantly lower than that of the healthy control group, and the MMP9 level was significantly higher than that of the healthy control group. MMP3 and MMP9 levels correlate with sleep disturbance and cognitive function in PD patients, respectively.
    Type of Medium: Online Resource
    ISSN: 1663-4365
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2558898-9
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  • 10
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 7 ( 2021-2-3)
    Abstract: Background: Atrial fibrillation (AF) is increasingly considered an age-related degenerative disease, whose process is associated with the development of impaired left atrial (LA) performance. However, the subtle dynamic changes of LA performance in AF during aging have yet to be fully elucidated. Atrial fibrosis is a key substrate for the development of AF, but the progression of fibrosis during aging and its relationship with LA dysfunction need to be further explored. Methods: A total of 132 control individuals and 117 persistent AF patients were prospectively studied. Subjects were further stratified into three age groups (age group 1: younger than 65 years, age group 2: between 65 and 79 years old, and age group 3: older than 80 years). The two-dimensional speckle tracking imaging was carried out for analyzing the alterations in LA function underlying LA remodeling, whereas electroanatomic mapping was performed to investigate LA fibrosis burden. In animal study, aged mice and young mice served as research subjects. Echocardiography and histological staining were used to assess LA performance and fibrosis burden, respectively. Results: Echocardiography showed progressive increases in LA dimension and LA stiffness index, and progressive decreases in LA global longitudinal strain and LA strain rates with advancing age in both AF and control cohorts, which was more prominent in AF cohort. Electroanatomic mapping showed progressive decrease in mean LA voltage and progressive increases in LA surface area, low-voltage area %, and LA volume with advancing age, whereas more significant alterations were observed in AF patients. Moreover, left atrial global longitudinal strain was positively correlated with mean LA voltage, whereas LA stiffness index was negatively related to mean LA voltage. In animal experiment, increased LA size and pulmonary artery dimension as well as longer P-wave duration and more prominent LA fibrosis were found in aged mice. Conclusions: This study provides new evidence of subtle changes in structure and performance of left atrium and their association with atrial fibrosis in both AF and non-AF subjects during physiological aging. In addition, our study also provides normal values for LA structure and performance in both AF and non-AF conditions during aging. These measurements may provide an early marker for onset of AF and LA adverse remodeling.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2781496-8
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