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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
    Online Resource
    Online Resource
    Honokiol Inhibits Proliferation, Invasion and Induces Apoptosis Through Targeting Lyn Kinase in Human Lung Adenocarcinoma Cells
    Frontiers Media SA ; 2018
    In:  Frontiers in Pharmacology Vol. 9 ( 2018-5-28)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 9 ( 2018-5-28)
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2018.00558
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 3
    Online Resource
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    Table_1.DOCX
    Frontiers Media SA ; 2021
    In:  Frontiers in Pediatrics Vol. 8 ( 2021-1-20)
    Details
    In: Frontiers in Pediatrics, Frontiers Media SA, Vol. 8 ( 2021-1-20)
    Abstract: Objective: This study was conducted to evaluate the potential genetic and non-genetic factors contributing to plasma trough concentration-to-dose ( C 0 / D ) ratio of valproic acid (VPA) in pediatric patients with epilepsy. Study Design: A single-center, retrospective cohort study was performed by collecting data from 194 children aged 1–14 years between May 2018 and November 2018. The oral solution ( n = 135) group and the sustained-release (SR) tablet group ( n = 59) were defined, and the plasma VPA C 0 was measured. Twenty-six single-nucleotide polymorphisms (SNPs) were chosen for genotyping with the MassARRAY system. A multiple logistic regression model was used for data analysis. Results: Body weight (BW) and age were positively correlated with the C 0 / D ratio in 194 patients, but the positive correlation disappeared after the patients were divided into oral solution and SR tablet subgroups. The average C 0 / D ratio was significantly increased by 2.11-fold ( P = 0.000) in children who took VPA SR tablets compared with children who were administered VPA oral solutions. No significant association between genetic variants and the C 0 / D ratio was found, even for the five well-studied SNPs, namely UGT2B7 G211T, C802T, C161T, T125C, and CYP2C9 * 3 A1075C. However, a significant association between the C 0 / D ratio and UGT1A6/9 Del & gt;A (rs144486213) was observed in the VPA oral solution group, but not in the VPA SR tablet group. Conclusions: The dosage forms of sodium valproate, rather than BW, age, or genetic polymorphisms, significantly affected the VPA C 0 / D ratios in pediatric patients with epilepsy. Based on our findings, switching the dosage form between solution and SR tablet should be performed cautiously. Total daily dose adjustment should be considered, and the plasma concentration, seizure-control effect, and adverse drug reaction should also be monitored very closely.
    Type of Medium: Online Resource
    ISSN: 2296-2360
    URL: Article
    URL: Article
    DOI: 10.3389/fped.2020.599044
    DOI: 10.3389/fped.2020.599044.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2711999-3
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  • 4
    Online Resource
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    Table_7.xlsx
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-3-3)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-3-3)
    Abstract: Pyroptosis is an inflammatory form of programmed cell death that is involved in various cancers, including hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) were recently verified as crucial mediators in the regulation of pyroptosis. However, the role of pyroptosis-related lncRNAs in HCC and their associations with prognosis have not been reported. In this study, we constructed a prognostic signature based on pyroptosis-related differentially expressed lncRNAs in HCC. A co-expression network of pyroptosis-related mRNAs–lncRNAs was constructed based on HCC data from The Cancer Genome Atlas. Cox regression analyses were performed to construct a pyroptosis-related lncRNA signature (PRlncSig) in a training cohort, which was subsequently validated in a testing cohort and a combination of the two cohorts. Kaplan–Meier analyses revealed that patients in the high-risk group had poorer survival times. Receiver operating characteristic curve and principal component analyses further verified the accuracy of the PRlncSig model. Besides, the external cohort validation confirmed the robustness of PRlncSig. Furthermore, a nomogram based on the PRlncSig score and clinical characteristics was established and shown to have robust prediction ability. In addition, gene set enrichment analysis revealed that the RNA degradation, the cell cycle, the WNT signaling pathway, and numerous immune processes were significantly enriched in the high-risk group compared to the low-risk group. Moreover, the immune cell subpopulations, the expression of immune checkpoint genes, and response to chemotherapy and immunotherapy differed significantly between the high- and low-risk groups. Finally, the expression levels of the five lncRNAs in the signature were validated by quantitative real-time PCR. In summary, our PRlncSig model shows significant predictive value with respect to prognosis of HCC patients and could provide clinical guidance for individualized immunotherapy.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.794034
    DOI: 10.3389/fonc.2022.794034.s001
    DOI: 10.3389/fonc.2022.794034.s002
    DOI: 10.3389/fonc.2022.794034.s003
    DOI: 10.3389/fonc.2022.794034.s004
    DOI: 10.3389/fonc.2022.794034.s005
    DOI: 10.3389/fonc.2022.794034.s006
    DOI: 10.3389/fonc.2022.794034.s007
    DOI: 10.3389/fonc.2022.794034.s008
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 5
    Online Resource
    Online Resource
    Increases prognostic value of clinical-pathological nomogram in patients with esophageal squamous cell carcinoma
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-2-14)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-2-14)
    Abstract: This study was intended to construct a brand new prognostic nomogram after combine clinical and pathological characteristics to increases prognostic value in patients with esophageal squamous cell carcinoma. Methods A total of 1,634 patients were included. Subsequently, the tumor tissues of all patients were prepared into tissue microarrays. AIPATHWELL software was employed to explore tissue microarrays and calculate the tumor-stroma ratio. X-tile was adopted to find the optimal cut-off value. Univariate and multivariate Cox analyses were used to screen out remarkable characteristics for constructing the nomogram in the total populations. A novel prognostic nomogram with clinical and pathological characteristics was constructed on the basis of the training cohort (n=1,144). What’s more performance was validated in the validation cohort (n=490). Clinical-pathological nomogram were assessed by concordance index, time-dependent receiver operating characteristic, calibration curve and decision curve analysis. Results The patients can divide into two groups with cut-off value of 69.78 for the tumor-stroma ratio. It is noteworthy that the survival difference was noticeable ( P & lt;0.001). A clinical-pathological nomogram was constructed by combining clinical and pathological characteristics to predict the overall survival. In comparison with TNM stage, the concordance index and time-dependent receiver operating characteristic of the clinical-pathological nomogram showed better predictive value ( P & lt;0.001). High quality of calibration plots in overall survival was noticed. As demonstrated by the decision curve analysis, the nomogram has better value than the TNM stage. Conclusions As evidently revealed by the research findings, tumor-stroma ratio is an independent prognostic factor in patients with esophageal squamous cell carcinoma. The clinical-pathological nomogram has an incremental value compared TNM stage in predicting overall survival.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2023.997776
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 6
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    Data_Sheet_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Cellular Neuroscience Vol. 16 ( 2022-5-11)
    Details
    In: Frontiers in Cellular Neuroscience, Frontiers Media SA, Vol. 16 ( 2022-5-11)
    Abstract: Heat stroke is the outcome of excessive heat stress, which results in core temperatures exceeding 40°C accompanied by a series of complications. The brain is particularly vulnerable to damage from heat stress. In our previous studies, both activated microglia and increased neuronal autophagy were found in the cortices of mice with heat stroke. However, whether activated microglia can accelerate neuronal autophagy under heat stress conditions is still unknown. In this study, we aimed to investigate the underlying mechanism that caused neuronal autophagy upregulation in heat stroke from the perspective of exosome-mediated intercellular communication. Methods In this study, BV2 and N2a cells were used instead of microglia and neurons, respectively. Exosomes were extracted from BV2 culture supernatants by ultracentrifugation and then characterized via transmission electron microscopy, nanoparticle tracking analysis and Western blotting. N2a cells pretreated with/without miR-155 inhibitor were cocultured with microglial exosomes that were treated with/without heat stress or miR-155 overexpression and subsequently subjected to heat stress treatment. Autophagy in N2a cells was assessed by detecting autophagosomes and autophagy-related proteins through transmission electron microscopy, immunofluorescence, and Western blotting. The expression of miR-155 in BV2 and BV2 exosomes and N2a cells was measured using real-time reverse transcription polymerase chain reaction. Target binding analysis was verified via a dual-luciferase reporter assay. Results N2a autophagy moderately increased in response to heat stress and accelerated by BV2 cells through transferring exosomes to neurons. Furthermore, we found that neuronal autophagy was positively correlated with the content of miR-155 in microglial exosomes. Inhibition of miR-155 partly abolished autophagy in N2a cells, which was increased by coculture with miR-155-upregulated exosomes. Mechanistic analysis confirmed that Rheb is a functional target of miR-155 and that microglial exosomal miR-155 accelerated heat stress-induced neuronal autophagy mainly by regulating the Rheb-mTOR signaling pathway. Conclusion Increased miR-155 in microglial exosomes after heat stroke can induce neuronal autophagy via their transfer into neurons. miR-155 exerted these effects by targeting Rheb, thus inhibiting the activity of mTOR signaling. Therefore, miR-155 could be a promising target for interventions of neuronal autophagy after heat stroke.
    Type of Medium: Online Resource
    ISSN: 1662-5102
    URL: Article
    URL: Article
    DOI: 10.3389/fncel.2022.865568
    DOI: 10.3389/fncel.2022.865568.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2452963-1
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  • 7
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    Data_Sheet_1.pdf
    Frontiers Media SA ; 2020
    In:  Frontiers in Neurology Vol. 11 ( 2020-9-17)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 11 ( 2020-9-17)
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    URL: Article
    DOI: 10.3389/fneur.2020.01036
    DOI: 10.3389/fneur.2020.01036.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2564214-5
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  • 8
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    DataSheet_8.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Immunology Vol. 12 ( 2021-9-28)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-9-28)
    Abstract: Intestinal ischemia/reperfusion (I/R) injury is a grave condition with high morbidity and mortality. We previously confirmed that intestinal I/R induces intestinal flora disorders and changes in metabolites, but the role of different metabolites in intestinal I/R injury is currently unclear. Based on targeted metabolic sequencing, pravastatin (PA) was determined to be a metabolite of the gut microbiota. Further, intestinal I/R model mice were established through superior mesenteric artery obstruction. In addition, a co-culture model of small intestinal organoids and type II innate lymphoid cells (ILC2s) was subjected to hypoxia/reoxygenation (H/R) to simulate an intestinal I/R model. Moreover, correlation analysis between the PA level in preoperative feces of patients undergoing cardiopulmonary bypass and the indices of postoperative intestinal I/R injury was carried out. IL-33-deficient mice, ILC2-deleted mice, and anti-IL-13 neutralizing antibodies were also used to explore the potential mechanism through which PA attenuates intestinal I/R injury. We demonstrated that PA levels in the preoperative stool of patients undergoing cardiopulmonary bypass were negatively correlated with the indices of postoperative intestinal I/R injury. Furthermore, PA alleviated intestinal I/R injury and improved the survival of mice. We further showed that PA promotes IL-13 release from ILC2s by activating IL-33/ST2 signaling to attenuate intestinal I/R injury. In addition, IL-13 promoted the self-renewal of intestinal stem cells by activating Notch1 and Wnt signals. Overall, results indicated that the gut microbial metabolite PA can attenuate intestinal I/R injury by promoting the release of IL-13 from ILC2s via IL-33/ST2 signaling, revealing a novel mechanism of and therapeutic strategy for intestinal I/R injury.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.704836
    DOI: 10.3389/fimmu.2021.704836.s001
    DOI: 10.3389/fimmu.2021.704836.s002
    DOI: 10.3389/fimmu.2021.704836.s003
    DOI: 10.3389/fimmu.2021.704836.s004
    DOI: 10.3389/fimmu.2021.704836.s005
    DOI: 10.3389/fimmu.2021.704836.s006
    DOI: 10.3389/fimmu.2021.704836.s007
    DOI: 10.3389/fimmu.2021.704836.s008
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 9
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    TREM2 Regulates Heat Acclimation-Induced Microglial M2 Polarization Involving the PI3K-Akt Pathway Following EMF Exposure
    Frontiers Media SA ; 2020
    In:  Frontiers in Cellular Neuroscience Vol. 13 ( 2020-1-15)
    Details
    In: Frontiers in Cellular Neuroscience, Frontiers Media SA, Vol. 13 ( 2020-1-15)
    Type of Medium: Online Resource
    ISSN: 1662-5102
    URL: Article
    DOI: 10.3389/fncel.2019.00591
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2452963-1
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  • 10
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    Table6.DOCX
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-3-7)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-3-7)
    Abstract: Aims: Liver disease has high prevalence, number, and disease burden in China, and polyene phosphatidyl choline (PPC) is a widely used liver protective drug. We aim to explore the effectiveness and economy of PPC in patients with liver diseases based on real-world research and compare with other hepatoprotective drugs. Methods: This is a “three-phase” study from three medical centers, including descriptive study of patients using PPC injection, self-control case study of patients using PPC injection, and specific-disease cohort study of patients using PPC injection or control drugs. The major measurements of liver function for effectiveness analysis were the alanine transaminase (ALT) level changes and recovery rate. The main statistical methods were Wilcoxon signed rank test, χ 2 test, and Mann–Whitney U test. Propensity score matching was applied to reduce bias. Cost-effectiveness analysis, cost minimization analysis, and sensitivity analysis were used for economic evaluation. Results: PPC alone or in combination with glutathione and magnesium isoglycyrrhizinate shows less total hospitalization cost ( p & lt; 0.05) and smaller cost-effectiveness ratio and was effective in protecting liver function, especially in patients with liver transplantation or postoperation of nontumor liver disease (ALT decreased significantly after PPC treatment; p & lt; 0.05). Glutathione and magnesium isoglycyrrhizinate combined with PPC could enhance the protective function of liver. Conclusion: PPC was an effective and economic liver protective drug in patients with specific liver diseases, and PPC could enhance the liver protective function of glutathione and magnesium isoglycyrrhizinate.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.806787
    DOI: 10.3389/fphar.2022.806787.s001
    DOI: 10.3389/fphar.2022.806787.s002
    DOI: 10.3389/fphar.2022.806787.s003
    DOI: 10.3389/fphar.2022.806787.s004
    DOI: 10.3389/fphar.2022.806787.s005
    DOI: 10.3389/fphar.2022.806787.s006
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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