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  • Frontiers Media SA  (26)
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  • 1
    Online Resource
    Online Resource
    DataSheet_1.zip
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-5-11)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-5-11)
    Abstract: Patients with Prader-Willi syndrome (PWS) have a reduced life expectancy due to inflammation-related disease including cardiovascular disease and diabetes. Abnormal activation of peripheral immune system is postulated as a contributor. However, detailed features of the peripheral immune cells in PWS have not been fully elucidated. Methods Serum inflammatory cytokines were measured in healthy controls (n=13) and PWS patients (n=10) using a 65- multiplex cytokine assays. Changes of the peripheral immune cells in PWS was assessed by single-cell RNA sequencing (scRNA-seq) and high-dimensional mass cytometry (CyTOF) using peripheral blood mononuclear cells (PBMCs) from PWS patients (n=6) and healthy controls (n=12). Results PWS patients exhibited hyper-inflammatory signatures in PBMCs and monocytes were the most pronounced. Most inflammatory serum cytokines were increased in PWS, including IL-1β, IL-2R, IL-12p70, and TNF-α. The characteristics of monocytes evaluated by scRNA-seq and CyTOF showed that CD16 + monocytes were significantly increased in PWS patients. Functional pathway analysis revealed that CD16 + monocytes upregulated pathways in PWS were closely associated with TNF/IL-1β- driven inflammation signaling. The CellChat analysis identified CD16 + monocytes transmitted chemokine and cytokine signaling to drive inflammatory process in other cell types. Finally, we explored the PWS deletion region 15q11–q13 might be responsible for elevated levels of inflammation in the peripheral immune system. Conclusion The study highlights that CD16 + monocytes contributor to the hyper-inflammatory state of PWS which provides potential targets for immunotherapy in the future and expands our knowledge of peripheral immune cells in PWS at the single cell level for the first time.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2023.1153730
    DOI: 10.3389/fimmu.2023.1153730.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
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  • 2
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    Prognostic Value of Coronary CT Angiography-Derived Fractional Flow Reserve in Non-obstructive Coronary Artery Disease: A Prospective Multicenter Observational Study
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 8 ( 2022-1-31)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 8 ( 2022-1-31)
    Abstract: Coronary artery disease (CAD) is a major contributor to morbidity and mortality worldwide. Myocardial ischemia may occur in patients with normal or non-obstructive CAD on invasive coronary angiography (ICA). The comprehensive evaluation of coronary CT angiography (CCTA) integrated with fractional flow reserve derived from CCTA (CT-FFR) to CAD may be essential to improve the outcomes of patients with non-obstructive CAD. China CT-FFR Study-2 (ChiCTR2000031410) is a large-scale prospective, observational study in 29 medical centers in China. The primary purpose is to uncover the relationship between the CCTA findings (including CT-FFR) and the outcome of patients with non-obstructive CAD. At least 10,000 patients with non-obstructive CAD but without previous revascularization will be enrolled. A 5-year follow-up will be performed. The primary endpoint is the occurrence of major adverse cardiovascular events (MACE), including all-cause mortality, non-fatal myocardial infarct, unplanned revascularization, and hospitalization for unstable angina. Clinical characteristics, laboratory and imaging examination results will be collected to analyze their prognostic value.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    DOI: 10.3389/fcvm.2021.778010
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 3
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    Table_1.xlsx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-12-20)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-12-20)
    Abstract: Observational studies have identified associations between smoking, alcohol use, body mass index (BMI), and the levels of vitamin D with primary biliary cholangitis (PBC). However, there was a lack of randomization control studies to estimate the causal relationship. This study was to investigate the causal estimates for the effects of those risk factors on PBC. Methods The genetic instrument variants were extracted from genome-wide association studies in European ancestry. Two-sample mendelian randomization (MR) and multivariable mendelian randomization were used to determine genetically causal estimates. Primary analyses consisted of random-effects and fix-mode inverse-variance-weighted methods, followed by secondary sensitivity analyses to verify the results. Results Our study showed that BMI was a causal factor for PBC (OR 1.35; 95% CI=1.03-1.77; p =0.029). In addition, we found that serum vitamin D levels had a protective effect on PBC after adjusting for BMI (OR 0.51; 95% CI=0.32-0.84; p =0.007). However, we failed to identify evidence supporting that genetic causal effect of smoking and alcohol intake were associated with PBC in European countries. Conclusion Our results enriched findings from previous epidemiology studies and provided evidence from MR that serum vitamin D concentrations and BMI were independent causal factors for PBC, suggesting that ensuing vitamin D sufficiency and healthy lifestyles might be a cost-effective measure for early intervention for PBC.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.1055953
    DOI: 10.3389/fimmu.2022.1055953.s001
    DOI: 10.3389/fimmu.2022.1055953.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 4
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    Table_9.xlsx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 12 ( 2022-1-17)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2022-1-17)
    Abstract: Epstein-Barr virus (EBV) is a human herpesvirus that latently infects approximately 95% of adults and is associated with a spectrum of human diseases including Infectious Mononucleosis and a variety of malignancies. However, understanding the pathogenesis, vaccines and antiviral drugs for EBV-associated disease has been hampered by the lack of suitable animal models. Tree shrew is a novel laboratory animal with a close phylogenetic relationship to primates, which is a critical advantage for many animal models for human disease, especially viral infections. Herein, we first identified the key residues in the CR2 receptor that bind the gp350 protein and facilitate viral entry. We found that tree shrew shares 100% sequence identity with humans in these residues, which is much higher than rabbits (50%) and rats (25%). In vitro analysis showed that B lymphocytes of tree shrews are susceptible to EBV infection and replication, as well as EBV-enhanced cell proliferation. Moreover, results of in vivo experiments show that EBV infection in tree shrews resembles EBV infection in humans. The infected animals exhibited transient fever and loss of weight accompanied by neutropenia and high viremia levels during the acute phase of the viral infection. Thereafter, tree shrews acted as asymptomatic carriers of the virus in most cases that EBV-related protein could be detected in blood and tissues. However, a resurgence of EBV infection occurred at 49 dpi. Nanopore transcriptomic sequencing of peripheral blood in EBV-infected animals revealed the dynamic changes in biological processes occurring during EBV primary infection. Importantly, we find that neutrophil function was impaired in tree shrew model as well as human Infectious Mononucleosis datasets (GSE85599 and GSE45918). In addition, retrospective case reviews suggested that neutropenia may play an important role in EBV escaping host innate immune response, leading to long-term latent infection. Our findings demonstrated that tree shrew is a suitable animal model to evaluate the mechanisms of EBV infection, and for developing vaccines and therapeutic drugs against EBV.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
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    DOI: 10.3389/fimmu.2021.789604
    DOI: 10.3389/fimmu.2021.789604.s001
    DOI: 10.3389/fimmu.2021.789604.s002
    DOI: 10.3389/fimmu.2021.789604.s003
    DOI: 10.3389/fimmu.2021.789604.s004
    DOI: 10.3389/fimmu.2021.789604.s005
    DOI: 10.3389/fimmu.2021.789604.s006
    DOI: 10.3389/fimmu.2021.789604.s007
    DOI: 10.3389/fimmu.2021.789604.s008
    DOI: 10.3389/fimmu.2021.789604.s009
    DOI: 10.3389/fimmu.2021.789604.s010
    DOI: 10.3389/fimmu.2021.789604.s011
    DOI: 10.3389/fimmu.2021.789604.s012
    DOI: 10.3389/fimmu.2021.789604.s013
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 5
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    Table_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-8-21)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-8-21)
    Abstract: An essential fact underlying the severity of Staphylococcus aureus ( S. aureus ) infection is the bicomponent leukocidins released by the pathogen to target and lyse host phagocytes through specific binding cell membrane receptors. However, little is known about the impact of post-transcriptional modification of receptors on the leukocidin binding. Method In this study, we used small interfering RNA library (Horizon/Dharmacon) to screen potential genes that affect leukocidin binding on receptors. The cell permeability was investigated through flow cytometry measuring the internalization of 4′,6-diamidino-2-phenylindole. Expression of C5a anaphylatoxin chemotactic receptor 1 (C5aR1), sulfated C5aR1 in, and binding of 6x-His–tagged Hemolysin C (HlgC) and Panton-Valentine leukocidin (PVL) slow-component to THP-1 cell lines was detected and analyzed via flow cytometry. Bacterial burden and Survival analysis experiment was conducted in WT and myeloid TPST-cko C57BL/6N mice. Results After short hairpin RNA (shRNA) knockdown of TPST2 gene in THP-1, HL-60, and RAW264.7, the cytotoxicity of HlgAB, HlgCB, and Panton–Valentine leukocidin on THP-1 or HL-60 cells was decreased significantly, and the cytotoxicity of HlgAB on RAW264.7 cells was also decreased significantly. Knockdown of TPST2 did not affect the C5aR1 expression but downregulated cell surface C5aR1 tyrosine sulfation on THP-1. In addition, we found that the binding of HlgC and LukS-PV on cell surface receptor C5aR1 was impaired in C5aR1 + TPST2 − and C5aR1 − TPST2 − cells. Phagocyte knockout of TPST2 protects mice from S. aureus infection and improves the survival of mice infected with S. aureus . Conclusion These results indicate that phagocyte TPST2 mediates the bicomponent leukocidin cytotoxicity by promoting cell membrane receptor sulfation modification that facilitates its binding to leukocidin S component.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2023.1242330
    DOI: 10.3389/fimmu.2023.1242330.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
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  • 6
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    A novel germline HAVCR2 (TIM-3) compound heterozygous mutation is related to hemophagocytic lymphohistiocytic syndrome in EBV-positive peripheral T-cell lymphoma (NOS) with down-regulated TIM-3 signaling
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-9-23)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-9-23)
    Abstract: Recently, it have been reported that Hepatitis A Virus-Cellular Receptor 2(HAVCR2,encoding T-cell immunoglobulin and Mucin-Containing Protein 3[TIM3] ) mutations are associated with severe hemophagocytic syndrome(HLH) in subcutaneous panniculitis-like T-cell lymphoma(SPTCL),and there are also frequent mutations in sporadic SPTCL, suggesting the individuals harboring HAVCR2(TIM-3) germline mutations are highly susceptible to familial or sporadic SPTCL. Here, we identify a novel germline compound heterozygous mutation of TIM-3 gene,c.245A & gt;G (p. Tyr82Cys ) and c.265C & gt;T(p. Arg89Cys) variations in a single familial case with EBV-positive peripheral T-cell lymphoma(NOS),accompanied HLH;we also detected Tyr82Cys germline mutation in TIM-3 gene in one sporadic patient with cutaneous T cell lymphoma. We screened the distributive frequencies for TIM-3 mutations in healthy controls(n=87), B-(n=79) or T-cell lymphoma(n=25) not SPTCL, and the results showed that the mutation was found in two out of 25 patients with T-cell lymphoma but was not detected in 79 patients with B-cell lymphoma nor in a group of 87 controls. The mRNA expression of TIM-3 on primary cells and transfected HEK293 cells reduced significantly, indicating Tyr82Cys and Arg89Cys mutations is a loss-of function mutations on TIM-3,resulting in a weakened TIM-3 signaling. Our results suggest Tyr82Cys TIM-3 germline mutations are not only limited in SPTCL, and also occurred in other types of T-cell lymphoma, especially complicated HLH. TIM-3 mutations may be an predisposing factor for T-cell lymphoma and molecular marker for auxiliary diagnosis in T cell lymphoma,especially complicated with HLH.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2022.870676
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 7
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    Survival Benefits for Pulmonary Adenocarcinoma With Malignant Pleural Effusion After Thoracoscopic Surgical Treatment: A Real-World Study
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-5-5)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-5-5)
    Abstract: Malignant cells in the pleural fluid or pleural metastasis are classified as stage IV non-small cell lung cancer. Radical surgery is generally considered not suitable for such patients. The aim of our study was to discuss the effectiveness of video-assisted thoracoscopic surgery (VATS) in such patients. Methods A retrospective analysis of the clinical records of 195 patients was performed. These patients were all diagnosed with locally advanced pulmonary adenocarcinomas with malignant pleural effusion (MPE, M1a) but no distant organ metastasis. The 195 patients included 96 patients who underwent VATS plus chemotherapy and 99 patients who received thoracic drainage plus chemotherapy. The baseline characteristics of the patients included age, gender, smoking history, Eastern Cooperative Oncology Group (ECOG) score, and number of chemotherapy cycles (2–4 cycles or & gt;4 cycles); we also analyzed clinical characteristics including the specific surgical options of the VATS group. Results In multivariate analysis, when compared to the thoracic drainage group, the VATS group remained significantly associated with the overall survival [HR=0.480 (95%CI 0.301-0.765)]; when compared to the lobectomy, the sub-lobectomy and the palliative surgery, remained significantly associated with the overall survival [HR=0.637 (95%CI 0.409-0.993) and HR=0.548 (95%CI 0.435-0.832), respectively] . The median survival time (MST) of patients who underwent VATS (n = 96, 49.2%) was 25 months (95% CI 22.373–27.627) whereas the patients who received thoracic drainage (n = 99, 50.8%) was 11 months (95% CI 9.978–12.022). For patients who underwent VATS, the MST of patients who received a lobectomy (n = 50, 52.1%) was 27 months (95% CI 22.432–31.568), the MST of patients who received a sub-lobectomy plus pleurodesis (n = 26, 27.1%) was 27 months (95% CI 19.157–34.843), and the MST of patients who received only pleurodesis (n = 20, 20.8%) was 12 months (95% CI 7.617–16.383). Conclusion For pulmonary adenocarcinomas with MPE, receiving a lobectomy or sub-lobectomy plus pleurodesis with VATS was associated with improved survival compared with patients who only received thoracic drainage and chemotherapy. Our results and previously published data may justify the use of VATS for treating pulmonary adenocarcinomas with MPE.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2022.843220
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 8
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    Convergent Functional Changes of Default Mode Network in Mild Cognitive Impairment Using Activation Likelihood Estimation
    Frontiers Media SA ; 2021
    In:  Frontiers in Aging Neuroscience Vol. 13 ( 2021-10-5)
    Details
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 13 ( 2021-10-5)
    Abstract: Background: Mild cognitive impairment (MCI) represents a transitional state between normal aging and dementia disorders, especially Alzheimer's disease (AD). The disruption of the default mode network (DMN) is often considered to be a potential biomarker for the progression from MCI to AD. The purpose of this study was to assess MRI-specific changes of DMN in MCI patients by elucidating the convergence of brain regions with abnormal DMN function. Methods: We systematically searched PubMed, Ovid, and Web of science for relevant articles. We identified neuroimaging studies by using amplitude of low frequency fluctuation /fractional amplitude of low frequency fluctuation (ALFF/fALFF), regional homogeneity (ReHo), and functional connectivity (FC) in MCI patients. Based on the activation likelihood estimation (ALE) algorithm, we carried out connectivity modeling of coordination-based meta-analysis and functional meta-analysis. Results: In total, this meta-analysis includes 39 articles on functional neuroimaging studies. Using computer software analysis, we discovered that DMN changes in patients with MCI mainly occur in bilateral inferior frontal lobe, right medial frontal lobe, left inferior parietal lobe, bilateral precuneus, bilateral temporal lobe, and parahippocampal gyrus (PHG). Conclusions: Herein, we confirmed the presence of DMN-specific damage in MCI, which is helpful in revealing pathology of MCI and further explore mechanisms of conversion from MCI to AD. Therefore, we provide a new specific target and direction for delaying conversion from MCI to AD.
    Type of Medium: Online Resource
    ISSN: 1663-4365
    URL: Article
    DOI: 10.3389/fnagi.2021.708687
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2558898-9
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  • 9
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    Data_Sheet_1.zip
    Frontiers Media SA ; 2021
    In:  Frontiers in Aging Neuroscience Vol. 13 ( 2021-7-26)
    Details
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 13 ( 2021-7-26)
    Abstract: Background Mild cognitive impairment (MCI) is an intermediate stage between normal aging and dementia. Amnestic MCI (aMCI) and non-amnestic MCI are the two subtypes of MCI with the former having a higher risk for progressing to Alzheimer's disease (AD). Compared with healthy elderly adults, individuals with MCI have specific functional alterations in the salience network (SN). However, no consistent results are documenting these changes. This meta-analysis aimed to investigate the specific functional alterations in the SN in MCI and aMCI. Methods: We systematically searched PubMed, Embase, and Web of Science for scientific neuroimaging literature based on three research methods, namely, functional connectivity (FC), regional homogeneity (ReHo), and the amplitude of low-frequency fluctuation or fractional amplitude of low-frequency fluctuation (ALFF/fALFF). Then, we conducted the coordinate-based meta-analysis by using the activation likelihood estimation algorithm. Results: In total, 30 functional neuroimaging studies were included. After extracting the data and analyzing it, we obtained specific changes in some brain regions in the SN including decreased ALFF/fALFF in the left superior temporal gyrus, the insula, the precentral gyrus, and the precuneus in MCI and aMCI; increased FC in the thalamus, the caudate, the superior temporal gyrus, the insula, and the cingulate gyrus in MCI; and decreased ReHo in the anterior cingulate gyrus in aMCI. In addition, as to FC, interactions of the SN with other networks including the default mode network and the executive control network were also observed mainly in the middle frontal gyrus and superior frontal gyrus in MCI and inferior frontal gyrus in aMCI. Conclusions: Specific functional alternations in the SN and interactions of the SN with other networks in MCI could be useful as potential imaging biomarkers for MCI or aMCI. Meanwhile, it provided a new insight in predicting the progression of health to MCI or aMCI and novel targets for proper intervention to delay the progression. Systematic Review Registration: [PROSPERO], identifier [No. CRD42020216259] .
    Type of Medium: Online Resource
    ISSN: 1663-4365
    URL: Article
    URL: Article
    DOI: 10.3389/fnagi.2021.695210
    DOI: 10.3389/fnagi.2021.695210.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 10
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    DataSheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 12 ( 2022-1-12)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2022-1-12)
    Abstract: Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection is the deadliest infectious disease and a global health problem. Macrophages (Mφs) and neutrophils that can phagocytose Mtb represent the first line of immune response to infection. Glycogen synthase kinase-3α/β (GSK-3α/β) represents a regulatory switch in host immune responses. However, the efficacy and molecular mechanisms of how GSK-3α/β interacts with Mtb infection in Mφs remain undefined. Here, we demonstrated that Mtb infection downregulated GSK-3α/β activity and promoted matrix metalloproteinase-1 (MMP-1) and MMP-9 expressions in Mφs derived from acute monocytic human leukemia THP-1 cells (THP-1-Mφs). We confirmed the upregulation of MMP-9 expression in tissues of TB patients compared with patients of chronic inflammation (CI). In THP-1-Mφs and C57BL/6 mice, GSK-3α/β inhibitor SB216763 significantly increased MMP-1/9 production and facilitated Mtb load, while MMP inhibitors blocked MMP-1/9 expression and Mtb infection. Consistently, GSK-3α/β silencing significantly increased MMP-1/9 expression and Mtb infection, while overexpression of GSK-3α/β and constitutive activated GSK-3α/β mutants significantly reduced MMP-1/9 expression and Mtb infection in THP-1-Mφs. MMP-1/9 silencing reduced Mtb infection, while overexpression of MMP-1/9 promoted Mtb infection in THP-1-Mφs. We further found that GSK-3α/β inhibition increased Mtb infection and MMP-1/9 expression was blocked by ERK1/2 inhibitor. Additionally, we showed that protein kinase C-δ (PKC-δ) and mammalian target of rapamycin (mTOR) reduced GSK-3α/β activity and promoted MMP-1/9 production in Mtb-infected THP-1-Mφs. In conclusion, this study suggests that PKC-δ-mTOR axis suppresses GSK-3α/β activation with acceleration of MMP-1/9 expression through phospho-ERK1/2. These results reveal a novel immune escape mechanism of Mtb and a novel crosstalk between these critical signaling pathways in anti-TB immunity.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.752466
    DOI: 10.3389/fimmu.2021.752466.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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