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  • Frontiers Media SA  (16)
  • 1
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    Image_1.tif
    Frontiers Media SA ; 2021
    In:  Frontiers in Molecular Biosciences Vol. 8 ( 2021-5-21)
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    In: Frontiers in Molecular Biosciences, Frontiers Media SA, Vol. 8 ( 2021-5-21)
    Abstract: Osteosarcoma is a frequent bone malignancy in children and young adults. Despite the availability of some prognostic biomarkers, most of them fail to accurately predict prognosis in osteosarcoma patients. In this study, we used bioinformatics tools and machine learning algorithms to establish an autophagy-related long non-coding RNA (lncRNA) signature to predict the prognosis of osteosarcoma patients. Methods We obtained expression and clinical data from osteosarcoma patients in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. We acquired an autophagy gene list from the Human Autophagy Database (HADb) and identified autophagy-related lncRNAs by co-expression analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the autophagy-related lncRNAs were conducted. Univariate and multivariate Cox regression analyses were performed to assess the prognostic value of the autophagy-related lncRNA signature and validate the relationship between the signature and osteosarcoma patient survival in an independent cohort. We also investigated the relationship between the signature and immune cell infiltration. Results We initially identified 69 autophagy-related lncRNAs, 13 of which were significant predictors of overall survival in osteosarcoma patients. Kaplan-Meier analyses revealed that the 13 autophagy-related lncRNAs could stratify patients based on their outcomes. Receiver operating characteristic curve analyses confirmed the superior prognostic value of the lncRNA signature compared to clinically used prognostic biomarkers. Importantly, the autophagy-related lncRNA signature predicted patient prognosis independently of clinicopathological characteristics. Furthermore, we found that the expression levels of the autophagy-related lncRNA signature were significantly associated with the infiltration levels of different immune cell subsets, including T cells, NK cells, and dendritic cells. Conclusion The autophagy-related lncRNA signature established here is an independent and robust predictor of osteosarcoma patient survival. Our findings also suggest that the expression of these 13 autophagy-related lncRNAs may promote osteosarcoma progression by regulating immune cell infiltration in the tumor microenvironment.
    Type of Medium: Online Resource
    ISSN: 2296-889X
    URL: Article
    URL: Article
    DOI: 10.3389/fmolb.2021.615084
    DOI: 10.3389/fmolb.2021.615084.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2814330-9
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  • 2
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Cell and Developmental Biology Vol. 9 ( 2021-5-26)
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    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 9 ( 2021-5-26)
    Abstract: The aim of this study was to construct a new immune-associated long non-coding RNA (lncRNA) signature to predict the prognosis of Ewing sarcoma (ES) and explore its molecular mechanisms. We downloaded transcriptome and clinical prognosis data from the Gene Expression Omnibus (GSE17679, which included 88 ES samples and 18 matched normal skeletal muscle samples), and used it as a training set to identify immune-related lncRNAs with different expression levels in ES. Univariable Cox regression was used to screen immune-related lncRNAs related to ES prognosis, and an immune-related lncRNA signature was constructed based on machine learning iterative lasso regression. An external verification set was used to confirm the predictive ability of the signature. Clinical feature subgroup analysis was used to explore whether the signature was an independent prognostic factor. In addition, CIBERSORT was used to explore immune cell infiltration in the high- and low-risk groups, and to analyze the correlations between the lncRNA signature and immune cell levels. Gene set enrichment and variation analyses were used to explore the possible regulatory mechanisms of the immune-related lncRNAs in ES. We also analyzed the expression of 17 common immunotherapy targets in the high- and low-risk groups to identify any that may be regulated by immune-related lncRNAs. We screened 35 immune-related lncRNAs by univariate Cox regression. Based on this, an immune-related 11-lncRNA signature was generated by machine learning iterative lasso regression. Analysis of the external validation set confirmed its high predictive ability. DPP10 antisense RNA 3 was negatively correlated with resting dendritic cell, neutrophil, and γδ T cell infiltration, and long intergenic non-protein coding RNA 1398 was positively correlated with resting dendritic cells and M2 macrophages. These lncRNAs may affect ES prognosis by regulating GSE17721_CTRL_VS_PAM3CSK4_12H_BMDC_UP, GSE2770_IL4_ACT_VS_ACT_CD4_TCELL_48H_UP, GSE29615_CTRL_VS_DAY3_ LAIV_IFLU_VACCINE_PBMC_UP, complement signaling, interleukin 2-signal transducer and activator of transcription 5 signaling, and protein secretion. The immune-related 11-lncRNA signature may also have regulatory effects on the immunotherapy targets CD40 molecule, CD70 molecule, and CD276 molecule. In conclusion, we constructed a new immune-related 11-lncRNA signature that can stratify the prognoses of patients with ES.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    URL: Article
    URL: Article
    DOI: 10.3389/fcell.2021.651593
    DOI: 10.3389/fcell.2021.651593.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2737824-X
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  • 3
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    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)
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    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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  • 4
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    Data_Sheet_1.PDF
    Frontiers Media SA ; 2023
    In:  Frontiers in Nutrition Vol. 10 ( 2023-2-27)
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    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 10 ( 2023-2-27)
    Abstract: Previous studies have shown that both hand grip strength (HGS) and the modified Glasgow Prognostic Score (mGPS) are associated with poor clinical outcomes in patients with liver cancer. In spite of this, no relevant studies have been conducted to determine whether the combination of HGS and mGPS can predict the prognosis of patients with liver cancer. Accordingly, this study sought to explore this possibility. Methods This was a multicenter study of patients with liver cancer. Based on the optimal HGS cutoff value for each sex, we determined the HGS cutoff values. The patients were divided into high and low HGS groups based on their HGS scores. An mGPS of 0 was defined as low mGPS, whereas scores higher than 0 were defined as high mGPS. The patients were combined into HGS-mGPS groups for the prediction of survival. Survival analysis was performed using Kaplan–Meier curves. A Cox regression model was designed and adjusted for confounders. To evaluate the nomogram model, receiver operating characteristic curves and calibration curves were used. Results A total of 504 patients were enrolled in this study. Of these, 386 (76.6%) were men (mean [SD] age, 56.63 [12.06] years). Multivariate analysis revealed that patients with low HGS and high mGPS had a higher risk of death than those with neither low HGS nor high mGPS (hazard ratio [HR],1.50; 95% confidenc e interval [CI],1.14–1.98; p  = 0.001 and HR, 1.55; 95% CI, 1.14–2.12, p  = 0.001 respectively). Patients with both low HGS and high mGPS had 2.35-fold increased risk of death (HR, 2.35; 95% CI, 1.52–3.63; p   & lt; 0.001). The area under the curve of HGS-mGPS was 0.623. The calibration curve demonstrated the validity of the HGS-mGPS nomogram model for predicting the survival of patients with liver cancer. Conclusion A combination of low HGS and high mGPS is associated with poor prognosis in patients with liver cancer. The combination of HGS and mGPS can predict the prognosis of liver cancer more accurately than HGS or mGPS alone. The nomogram model developed in this study can effectively predict the survival outcomes of liver cancer.
    Type of Medium: Online Resource
    ISSN: 2296-861X
    URL: Article
    URL: Article
    DOI: 10.3389/fnut.2023.1062117
    DOI: 10.3389/fnut.2023.1062117.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2776676-7
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  • 5
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    Perspectives of herbs and their natural compounds, and herb formulas on treating diverse diseases through regulating complicated JAK/STAT signaling
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-10-17)
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    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-10-17)
    Abstract: JAK/STAT signaling pathways are closely associated with multiple biological processes involved in cell proliferation, apoptosis, inflammation, differentiation, immune response, and epigenetics. Abnormal activation of the STAT pathway can contribute to disease progressions under various conditions. Moreover, tofacitinib and baricitinib as the JAK/STAT inhibitors have been recently approved by the FDA for rheumatology disease treatment. Therefore, influences on the STAT signaling pathway have potential and perspective approaches for diverse diseases. Chinese herbs in traditional Chinese medicine (TCM), which are widespread throughout China, are the gold resources of China and have been extensively used for treating multiple diseases for thousands of years. However, Chinese herbs and herb formulas are characterized by complicated components, resulting in various targets and pathways in treating diseases, which limits their approval and applications. With the development of chemistry and pharmacology, active ingredients of TCM and herbs and underlying mechanisms have been further identified and confirmed by pharmacists and chemists, which improved, to some extent, awkward limitations, approval, and applications regarding TCM and herbs. In this review, we summarized various herbs, herb formulas, natural compounds, and phytochemicals isolated from herbs that have the potential for regulating multiple biological processes via modulation of the JAK/STAT signaling pathway based on the published work. Our study will provide support for revealing TCM, their active compounds that treat diseases, and the underlying mechanism, further improving the rapid spread of TCM to the world.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2022.993862
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
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  • 6
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    Cerebral Ischemia-Reperfusion Is Associated With Upregulation of Cofilin-1 in the Motor Cortex
    Frontiers Media SA ; 2021
    In:  Frontiers in Cell and Developmental Biology Vol. 9 ( 2021-3-11)
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    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 9 ( 2021-3-11)
    Abstract: Cerebral ischemia is one of the leading causes of death. Reperfusion is a critical stage after thrombolysis or thrombectomy, accompanied by oxidative stress, excitotoxicity, neuroinflammation, and defects in synapse structure. The process is closely related to the dephosphorylation of actin-binding proteins (e.g., cofilin-1) by specific phosphatases. Although studies of the molecular mechanisms of the actin cytoskeleton have been ongoing for decades, limited studies have directly investigated reperfusion-induced reorganization of actin-binding protein, and little is known about the gene expression of actin-binding proteins. The exact mechanism is still uncertain. The motor cortex is very important to save nerve function; therefore, we chose the penumbra to study the relationship between cerebral ischemia-reperfusion and actin-binding protein. After transient middle cerebral artery occlusion (MCAO) and reperfusion, we confirmed reperfusion and motor function deficit by cerebral blood flow and gait analysis. PCR was used to screen the high expression mRNAs in penumbra of the motor cortex. The high expression of cofilin in this region was confirmed by immunohistochemistry (IHC) and Western blot (WB). The change in cofilin-1 expression appears at the same time as gait imbalance, especially maximum variation and left front swing. It is suggested that cofilin-1 may partially affect motor cortex function. This result provides a potential mechanism for understanding cerebral ischemia-reperfusion.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    URL: Article
    DOI: 10.3389/fcell.2021.634347
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 7
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    Table_1.xlsx
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-9-11)
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    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-9-11)
    Abstract: Advanced intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor of biliary epithelial cells, known for its extremely unfavorable prognosis. In the absence of intervention, patients typically survive for less than 5 months. Current guidelines from the Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO) recommend chemotherapy-based systemic therapy as the standard treatment for advanced ICC. However, the first-line regimen, consisting of gemcitabine in combination with cisplatin, generally results in a median survival of approximately one year, which is considered suboptimal. Significant progress has been made in radiotherapy techniques, molecular diagnostics, and tumor immune microenvironments. The integration of immune and radiation therapies has revolutionized treatment strategies for cholangiocarcinoma. Moreover, combined therapeutic regimens have shown promising results in improving survival rates among patients with advanced ICC. In this study, we present a case report of a 70-year-old male patient diagnosed with stage IV ICC, featuring metastases to the retroperitoneal, left adrenal, and left supraclavicular lymph nodes. The patient exhibited a high tumor mutational load, significant microsatellite instability, and hyper-expression of PD-L1 (90%), along with positive Epstein-Barr virus-encoded RNA (EBER). Pembrolizumab, a programmed cell death 1 (PD-1) inhibitor, was administered in conjunction with radiotherapy. As a result, considerable shrinkage and inactivation of the primary foci were observed, accompanied by the disappearance of metastases. Ultimately, the patient achieved complete remission and maintained progression-free survival for 41 months following the initial treatment. To the best of our knowledge, this represents the longest case of complete remission using a combination of immunotherapy and radiotherapy as a first-line regimen for the high tumor mutational load, microsatellite instability, and PD-L1 expression (90%) subtype of Epstein-Barr virus-associated ICC (EBVaICC). These findings suggest that the combination of PD-1 inhibitors with radiotherapy may serve as a promising therapeutic strategy for treating this particular cancer subtype.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2023.1239168
    DOI: 10.3389/fimmu.2023.1239168.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 8
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    Table_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-8-30)
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    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-8-30)
    Abstract: Limited evidence was available on the association of the integrated effect of multidimensional lifestyle factors with mortality among Chinese populations. This cohort study was to examine the effect of combined lifestyle factors on the risk of mortality by highlighting the number of healthy lifestyles and their overall effects. Methods A total of 11,395 participants from the Guangzhou Heart Study (GZHS) were followed up until 1 January 2020. Individual causes of death were obtained from the platform of the National Death Registry of China. The healthy lifestyle index (HLI) was established from seven dimensions of lifestyle, and lifestyle patterns were extracted from eight dimensions of lifestyle using principal component analysis (PCA). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard regression model. Results During 35,837 person-years of follow-up, 184 deaths (1.61%) were observed, including 64 from cardiovascular disease. After adjustment for confounders, HLI was associated with a 50% (HR: 0.50, 95% CI: 0.25–0.99) reduced risk of all-cause mortality when comparing the high (6–7 lifestyle factors) with low (0–2 lifestyle factors) categories. Three lifestyle patterns were defined and labeled as pattern I, II, and III. Lifestyle pattern II with higher factor loadings of non-smoking and low-level alcohol drinking was associated with a decreased risk of all-cause mortality (HR: 0.63, 95% CI: 0.43–0.92, P –trend = 0.023) when comparing the high with low tertiles of pattern score, after adjustment for confounders. Every 1-unit increment of pattern II score was associated with a decreased risk (HR: 0.97, 95% CI: 0.95–0.99) of all-cause mortality. The other two patterns were not associated with all-cause mortality, and the association of cardiovascular mortality risk was observed with neither HLI nor any lifestyle pattern. Conclusion The results suggest that the more dimensions of the healthy lifestyle the lower the risk of death, and adherence to the lifestyle pattern characterized with heavier loading of non-smoking and low-level alcohol drinking reduces the risk of all-cause mortality. The findings highlight the need to consider multi-dimensional lifestyles rather than one when developing health promotion strategies.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2022.920760
    DOI: 10.3389/fmed.2022.920760.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 9
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    Relationship Between Heart Rate Variability and Pulse Rate Variability Measures in Patients After Coronary Artery Bypass Graft Surgery
    Frontiers Media SA ; 2021
    In:  Frontiers in Cardiovascular Medicine Vol. 8 ( 2021-12-16)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 8 ( 2021-12-16)
    Abstract: Background: Heart rate variability (HRV) and pulse rate variability (PRV) measures are two kinds of physiological indices that can be used to evaluate the autonomic nervous function of healthy subjects and patients with various kinds of illness. Purpose: In this study, we compared the agreement and linear relationship between electrocardiographic signals (ECG)-derived HRV and photoplethysmographic signals (PPG)-derived right hand PRV (R-PRV) and left hand PRV (L-PRV) measures in 14 patients over 1 year after coronary artery bypass graft (CABG) surgery. Method: The ECG and PPG signals of the patient were recorded simultaneously for 10 min in a supine position. The last 512 stationary RR intervals (RRI) and peak-to peak intervals (PPI) of pulse wave were derived for data analysis. Bland-Altman plot was used to assess the agreement among HRV and both hand PRV measures, while linear regression analysis was used to examine the relationship among corresponding measures of HRV, R-PRV, and L-PRV. Result: The results revealed significant differences in total power (TP), very low-frequency power (VLF), low-frequency power (LF), high-frequency power (HF), and normalized VLF (VLFnorm) among HRV, R-PRV, and L-PRV. Bland-Altman plot analysis showed good agreements in almost all measures between R-PRV and L-PRV, except insufficient agreement was found in LF/HF. Insufficient agreements were found in root mean square successive difference (RMSSD), normalized HF (HFnorm), and LF/HF indices between HRV and L-PRV, and in VLFnorm, HFnorm, and LF/HF indices between HRV and R-PRV. Linear regression analysis showed that the HRV, R-PRV, and L-PRV measures were all highly correlated with one another ( r = 0.94 ~ 1; p & lt; 0.001). Conclusion: Though PRV measures of either hand are not surrogates of HRV measures, they might still be used to evaluate the autonomic nervous functions of CABG patients due to the moderate to good agreements in most time-domain and frequency-domain HRV measures and the strong and positive correlations among HRV and both hands PRV measures in CABG patients.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    DOI: 10.3389/fcvm.2021.749297
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2781496-8
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  • 10
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    Transcriptional regulation of macrophages in heart failure
    Frontiers Media SA ; 2023
    In:  Frontiers in Cardiovascular Medicine Vol. 10 ( 2023-3-30)
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    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 10 ( 2023-3-30)
    Abstract: Adverse cardiac remodeling after acute myocardial infarction is the most important pathological mechanism of heart failure and remains a major problem in clinical practice. Cardiac macrophages, derived from tissue resident macrophages and circulating monocyte, undergo significant phenotypic and functional changes following cardiac injury and play crucial roles in inflammatory response and tissue repair response. Currently, numerous studies indicate that epigenetic regulatory factors and transcription factors can regulate the transcription of inflammatory and reparative genes and timely conversion of inflammatory macrophages into reparative macrophages and then alleviate cardiac remodeling. Accordingly, targeting transcriptional regulation of macrophages may be a promising option for heart failure treatment. In this review, we not only summarize the origin and function of cardiac macrophages, but more importantly, describe the transcriptional regulation of macrophages in heart failure, aiming to provide a potential therapeutic target for heart failure.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    DOI: 10.3389/fcvm.2023.1148041
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2781496-8
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