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  • Frontiers Media SA  (401)
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  • Frontiers Media SA  (401)
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  • 1
    Online Resource
    Online Resource
    Human Umbilical Cord Mesenchymal Stem Cells to Treat Neuromyelitis Optica Spectrum Disorder (hUC–MSC–NMOSD): A Study Protocol for a Prospective, Multicenter, Randomized, Placebo-Controlled Clinical Trial
    Frontiers Media SA ; 2022
    In:  Frontiers in Neurology Vol. 13 ( 2022-4-25)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-4-25)
    Abstract: Neuromyelitis Optica spectrum disorder (NMOSD) is severe relapsing and disabling autoimmune disease of the central nervous system. Its optimal first-line treatment to reduce relapse rate and ameliorate neurological disability remains unclear. We will conduct a prospective, multicenter, randomized, placebo-controlled clinical trial to study the safety and effectiveness of human umbilical cord mesenchymal stem cells (hUC–MSCs) in treating NMOSD. Methods The trial is planned to recruit 430 AQP4-IgG seropositive NMOSD patients. It consists of three consecutive stages. The first stage will be carried out in the leading center only and aims to evaluate the safety of hUC—MSCs. Patients will be treated with three different doses of hUC–MSCs: 1, 2, or 5 × 10 6 MSC/kg·weight for the low-, medium-, and high-dose group, respectively. The second and third stages will be carried out in six centers. The second stage aims to find the optimal dosage. Patients will be 1:1:1:1 randomized into the low-, medium-, high-dose group and the controlled group. The third stage aims to evaluate the effectiveness. Patients will be 1:1 randomized into the optimal dose and the controlled group. The primary endpoint is the first recurrent time and secondary endpoints are the recurrent times, EDSS scores, MRI lesion numbers, OSIS scores, Hauser walking index, and SF-36 scores. Endpoint events and side effects will be evaluated every 3 months for 2 years. Discussion Although hUC–MSC has shown promising treatment effects of NMOSD in preclinical studies, there is still a lack of well-designed clinical trials to evaluate the safety and effectiveness of hUC–MSC among NMOSD patients. As far as we know, this trial will be the first one to systematically demonstrate the clinical safety and efficacy of hUC–MSC in treating NMOSD and might be able to determine the optimal dose of hUC–MSC for NMOSD patients. Trial registration The study was registered with the Chinese Clinical Trial Registry ( CHICTR.org.cn ) on 2 March 2016 (registration No. ChiCTR-INR-16008037), and the revised trial protocol (Protocol version 1.2.1) was released on 16 March 2020.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    DOI: 10.3389/fneur.2022.860083
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564214-5
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  • 2
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    Online Resource
    DWPPI: A Deep Learning Approach for Predicting Protein–Protein Interactions in Plants Based on Multi-Source Information With a Large-Scale Biological Network
    Frontiers Media SA ; 2022
    In:  Frontiers in Bioengineering and Biotechnology Vol. 10 ( 2022-3-21)
    Details
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 10 ( 2022-3-21)
    Abstract: The prediction of protein–protein interactions (PPIs) in plants is vital for probing the cell function. Although multiple high-throughput approaches in the biological domain have been developed to identify PPIs, with the increasing complexity of PPI network, these methods fall into laborious and time-consuming situations. Thus, it is essential to develop an effective and feasible computational method for the prediction of PPIs in plants. In this study, we present a network embedding-based method, called DWPPI, for predicting the interactions between different plant proteins based on multi-source information and combined with deep neural networks (DNN). The DWPPI model fuses the protein natural language sequence information (attribute information) and protein behavior information to represent plant proteins as feature vectors and finally sends these features to a deep learning–based classifier for prediction. To validate the prediction performance of DWPPI, we performed it on three model plant datasets: Arabidopsis thaliana ( A. thaliana ), mazie ( Zea mays ), and rice ( Oryza sativa ). The experimental results with the fivefold cross-validation technique demonstrated that DWPPI obtains great performance with the AUC (area under ROC curves) values of 0.9548, 0.9867, and 0.9213, respectively. To further verify the predictive capacity of DWPPI, we compared it with some different state-of-the-art machine learning classifiers. Moreover, case studies were performed with the AC149810.2_FGP003 protein. As a result, 14 of the top 20 PPI pairs identified by DWPPI with the highest scores were confirmed by the literature. These excellent results suggest that the DWPPI model can act as a promising tool for related plant molecular biology.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    URL: Article
    DOI: 10.3389/fbioe.2022.807522
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2719493-0
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  • 3
    Online Resource
    Online Resource
    DataSheet_2.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Cellular and Infection Microbiology Vol. 12 ( 2022-3-7)
    Details
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 12 ( 2022-3-7)
    Abstract: Epstein–Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct entity with a conspicuous tumor microenvironment compared with EBV-negative gastric carcinoma. However, the exact role of EBV in gastric carcinogenesis remains elusive. In the present study, we found that EBV upregulated CXCL8 expression, and CXCL8 significantly promoted vasculogenic mimicry (VM) formation of gastric carcinoma (GC) cells. In accordance with these observations, overexpression of CXCL8 increased cell proliferation and migration of AGS and BGC823 cells, while knockdown of CXCL8 with siRNA inhibited cell proliferation and migration of AGS-EBV cells. In addition, activation of NF-κB signaling was involved in VM formation induced by CXCL8, which was blocked by NF-κB inhibitors BAY 11-7082 and BMS345541. Furthermore, EBV-encoded lncRNA RPMS1 activated the NF-κB signaling cascade, which is responsible for EBV-induced VM formation. Both xenografts and clinical samples of EBVaGC exhibit VM histologically, which are correlated with CXCL8 overexpression. Finally, CXCL8 is positively correlated with overall survival in GC patients. In conclusion, EBV-upregulated CXCL8 expression promotes VM formation in GC via NF-κB signaling, and CXCL8 might serve as a novel anti-tumor target for EBVaGC.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fcimb.2022.780416
    DOI: 10.3389/fcimb.2022.780416.s001
    DOI: 10.3389/fcimb.2022.780416.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2619676-1
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  • 4
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    Online Resource
    DataSheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-3-25)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-3-25)
    Abstract: Triple-negative breast cancer (TNBC) is refractory and heterogeneous, comprising various entities with divergent phenotype, biology, and clinical presentation. As an aggressive subtype, Chinese TNBC patients with special morphologic patterns (STs) were restricted to its incidence of 10-15% in total TNBC population. Methods We recruited 89 patients with TNBC at Guangdong Provincial People’s Hospital (GDPH) from October 2014 to May 2021, comprising 72 cases of invasive ductal carcinoma of no-special type (NSTs) and 17 cases of STs. The clinical data of these patients was collected and statistically analyzed. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matched blood samples were collected for targeted next-generation sequencing (NGS) with cancer-related, 520- or 33-gene assay. Immunohistochemical analysis of FFPE tissue sections was performed using anti-programmed cell death-ligand 1(PD-L1) and anti-androgen receptor antibodies. Results Cases with NSTs presented with higher histologic grade and Ki-67 index rate than ST patients (NSTs to STs: grade I/II/III 1.4%, 16.7%,81.9% vs 0%, 29.4%, 58.8%; p & lt;0.05; Ki-67 ≥30%: 83.3% vs. 58.8%, p & lt;0.05), while androgen receptor (AR) and PD-L1 positive (combined positive score≥10) rates were lower than of STs cases (AR: 11.1% vs. 47.1%; PD-L1: 9.6% vs. 33.3%, p & lt;0.05). The most commonly altered genes were TP53 (88.7%), PIK3CA (26.8%), MYC (18.3%) in NSTs, and TP53 (68.8%), PIK3CA (50%), JAK3 (18.8%), KMT2C (18.8%) in STs respectively. Compared with NSTs, PIK3CA and TP53 mutation frequency showed difference in STs (47.1% vs 19.4%, p=0.039; 64.7% vs 87.5%, p=0.035). Conclusions In TNBC patients with STs, decrease in histologic grade and ki-67 index, as well as increase in PD-L1 and AR expression were observed when compared to those with NSTs, suggesting that TNBC patients with STs may better benefit from immune checkpoint inhibitors and/or AR inhibitors. Additionally, lower TP53 and higher PIK3CA mutation rates were also found in STs patients, providing genetic evidence for deciphering at least partly potential mechanism of action.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.830124
    DOI: 10.3389/fonc.2022.830124.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 5
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    Online Resource
    DataSheet3.xlsx
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 12 ( 2022-1-25)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2022-1-25)
    Abstract: Sulfur Angelicae Dahuricae Radix (Baizhi) is a common medicinal herb in Asian countries. A practical protocol combining metabolomics, pharmacology, and cytotoxicity was developed to comprehensively evaluate the influence of sulfur-fumigation on the quality of Baizhi. Furocoumarins could be transformed into sulfur-containing compounds during the sulfuring process, among which 1 and 3 were purified with relatively high abundance and identified as 3,4-dihydrobyakangelicin-4-sulfonic acid and (4 R ,12 S )-3,4-dihydrooxypeucedanin hydrate-4-sulfonic acid (OXH-S), respectively. OXH-S was found to be an addition product of sulfite and oxypeucedanin hydrate (OXH-N). Then, the cytotoxicity and anti-inflammatory activity of OXH-N, OXH-S, and water extracts of sulfured (extraction-S), and unsulfured Baizhi (extraction-N) were evaluated. OXH-S and extraction-S were less toxic than OXH-N and extraction-N, respectively. A comparison of OXH-N with OXH-S and extraction-N with extraction-S showed no significant differences in anti-inflammatory activity. These results suggest that sulfur fumigation can reduce toxicity and does not influence the anti-inflammatory activity of Baizhi, even after chemical composition changes. The proposed protocol based on marker screening, pharmacology, and safety evaluation provides a scientific basis for the standardization and regulation of sulfured Baizhi and other medical materials.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2021.799504
    DOI: 10.3389/fphar.2021.799504.s001
    DOI: 10.3389/fphar.2021.799504.s002
    DOI: 10.3389/fphar.2021.799504.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 6
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    Online Resource
    DataSheet2.xlsx
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-9-6)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-9-6)
    Abstract: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. TNBC exists widely reprogrammed lipid metabolism, and its metabolic-associated proteins and oncometabolites are promising as potential therapeutic targets. Dandelion ( Taraxacum mongolicum ) is a classical herbal medicine used to treat breast diseases based on traditional Chinese medicine theory and was reported to have antitumor effects and lipid regulatory capacities. Our previous study showed that dandelion extract was effective against TNBC. However, whether dandelion extract could regulate the lipid metabolisms of TNBC and exert its antitumor effects via interfering with lipids metabolism remained unclear. In this study, an integrated approach combined with network pharmacology and multi-omics techniques (including proteomics, metabolomics, and lipidomics) was performed to investigate the potential regulatory mechanisms of dandelion extract against TNBC. We first determined the antitumor effects of dandelion extract in vitro and in vivo . Then, network pharmacology analysis speculated the antitumor effects involving various metabolic processes, and the multi-omics results of the cells, tumor tissues, and plasma revealed the changes in the metabolites and metabolic-associated proteins after dandelion extract treatment. The alteration of glycerophospholipids and unsaturated fatty acids were the most remarkable types of metabolites. Therefore, the metabolism of glycerophospholipids and unsaturated fatty acids, and their corresponding proteins CHKA and FADS2, were considered the primary regulatory pathways and biomarkers of dandelion extract against TNBC. Subsequently, experimental validation showed that dandelion extract decreased CHKA expression, leading to the inhibition of the PI3K/AKT pathway and its downstream targets, SREBP and FADS2. Finally, the molecular docking simulation suggested that picrasinoside F and luteolin in dandelion extract had the most highly binding scores with CHKA, indicating they may be the potential CHKA inhibitors to regulate glycerophospholipids metabolisms of TNBC. In conclusion, we confirmed the antitumor effects of dandelion extract against TNBC cells in vitro and demonstrated that dandelion extract could interfere with glycerophospholipids and unsaturated fatty acids metabolism via downregulating the CHKA expression and inhibiting PI3K/AKT/SREBP/FADS2 axis.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.942996
    DOI: 10.3389/fphar.2022.942996.s001
    DOI: 10.3389/fphar.2022.942996.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 7
    Online Resource
    Online Resource
    Table_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Cellular and Infection Microbiology Vol. 11 ( 2021-7-6)
    Details
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 11 ( 2021-7-6)
    Abstract: Filamentous fungi identification by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been challenging due to the lack of simple and rapid protein extraction methods and insufficient species coverage in the database. In this study, we created two rapid protein extraction methods for filamentous fungi: a one-step zirconia-silica beads method (ZSB) and a focused-ultrasonication method (FUS). The identification accuracy of two methods were evaluated with the VITEK MS, as well as number of spectra peaks and signal-to-noise ratio (S/N) with M-Discover 100 MALDI-TOF MS compared to the routine method. The better method was applied to build a filamentous fungi in-house spectra library for the M-Discover 100 MS, and then another one and routine method were performed in parallel to verify the accuracy and commonality of the in-house library. Using the two optimized methods, the dedicated operating time before MALDI-TOF MS analysis was reduced from 30 min to 7 (ZSB) or 5 (FUS) min per sample, with only a few seconds added for each additional strain. And both two methods identified isolates from most mold types equal to or better than the routine method, and the total correct identification rate using VITEK MS was 79.67, 76.42, and 76.42%, respectively. On the other hand, the two rapid methods generally achieved higher maximum and minimum S/N ratios with these isolates tested as compared to the routine method. Besides, the ZSB method produced overall mean of maximum and minimum S/N ratio higher than that by FUS. An in-house library of M-Discover MS was successfully built from 135 isolates from 42 species belonging to 18 genera using the ZSB method. Analysis of 467 isolates resulted in 97.22% correctly identified isolates to the species level by the ZSB method versus 95.50% by the routine method. The two novel methods are time- and cost-effective and allow efficient identification of filamentous fungi while providing a simplified procedure to build an in-house library. Thus, more clinical laboratories may consider adopting MALDI-TOF MS for filamentous fungi identification in the future.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    URL: Article
    URL: Article
    DOI: 10.3389/fcimb.2021.687240
    DOI: 10.3389/fcimb.2021.687240.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2619676-1
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  • 8
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    Online Resource
    Stimulation of α7 Nicotinic Acetylcholine Receptor by Nicotine Suppresses Decidual M1 Macrophage Polarization Against Inflammation in Lipopolysaccharide-Induced Preeclampsia-Like Mouse Model
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-4-28)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-4-28)
    Abstract: Changes in decidual macrophage polarization affect local inflammatory microenvironment and lead to adverse pregnancy outcomes. However, the regulatory mechanism of macrophage polarization in preeclampsia (PE) remains unclear. In this study, we found that α7nAChR expression was significantly down-regulated in decidual macrophages in PE patients compared to normal pregnant women, accompanied by a reduced proportion of M2 phenotype and an increased proportion of M1 phenotype; these results suggested that the reduced α7nAChR activity might contribute to changes in the polarization of decidual macrophages. Then, we further investigated the regulatory role of α7nAChR activation by nicotine on decidual macrophage polarization and placental remodeling in the PE-like mouse model. The PE mice were obtained by i.p. injection of 10 µg/kg lipopolysaccharide (LPS) gestational day (GD) 13, and 40 µg/kg LPS daily until GD16. Subcutaneous injection of 1.0 mg/kg nicotine was administrated from GD14 to GD18. Nicotine treatment increased the decreased M2 phenotype and inhibited the increased M1 phenotype in decidua of pregnant mice induced by LPS. The levels of pro-inflammatory cytokines in decidua were higher but the levels of anti-inflammatory cytokines were lower in PE mice compared to the controls, nicotine reversed these changes. The level of choline acetyltransferase (CHAT) was reduced in the LPS-treated group, it was increased following nicotine treatment. Damage of spiral artery remodeling and down-regulation of markers related to trophoblast invasion in placentas were found in PE mice; nicotine improved these pathological structures of placentas. α-bungarotoxin (α-BGT) which is specific antagonist for α7nAChR could abolish the effects of nicotine on decidual macrophage polarization, trophoblast arrangement and vascular structure in placental tissue in PE mice. These results suggest that α7nAChR plays an important regulatory role in maternal-fetal inflammation and placental remodeling in preeclampsia and may provide a theoretical basis for the discovery of new strategies for preeclampsia.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2021.642071
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 9
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    Online Resource
    Table_1.PDF
    Frontiers Media SA ; 2018
    In:  Frontiers in Neurology Vol. 8 ( 2018-1-19)
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    In: Frontiers in Neurology, Frontiers Media SA, Vol. 8 ( 2018-1-19)
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fneur.2017.00755
    DOI: 10.3389/fneur.2017.00755.s001
    DOI: 10.3389/fneur.2017.00755.s002
    DOI: 10.3389/fneur.2017.00755.s003
    DOI: 10.3389/fneur.2017.00755.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2564214-5
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  • 10
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    Online Resource
    Image_1.pdf
    Frontiers Media SA ; 2020
    In:  Frontiers in Immunology Vol. 11 ( 2020-9-2)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 11 ( 2020-9-2)
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2020.01926
    DOI: 10.3389/fimmu.2020.01926.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2606827-8
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