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  • Frontiers Media SA  (10)
  • Deng, Jing  (10)
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  • Frontiers Media SA  (10)
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  • 1
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-10-11)
    Abstract: Targeted therapies such as oral tyrosine kinase inhibitors (TKIs) are the main therapeutic strategy effective for advanced hepatocellular carcinoma (HCC). Currently six tyrosine kinase inhibitors for HCC therapy have been approved. The newly approved first-line drug donafenib represent the major milestones in HCC therapeutics in recent years. However, drug resistance in HCC remains challenging due to random mutations in target receptors as well as downstream pathways. TKIs-based combinatorial therapies with immune checkpoint inhibitors such as PD-1/PD-L1 antibodies afford a promising strategy to further clinical application. Recent developments of nanoparticle-based TKI delivery techniques improve drug absorption and bioavailability, enhance efficient targeting delivery, prolonged circulation time, and reduce harmful side effects on normal tissues, which may improve the therapeutic efficacy of the TKIs. In this review, we summarize the milestones and recent progress in clinical trials of TKIs for HCC therapy. We also provide an overview of the novel nanoparticle-based TKI delivery techniques that enable efficient therapy.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-6-10)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-6-10)
    Abstract: Islet transplantation to treat the late stage of type 1 diabetic patient (T1DM) has recently made inspiring success in clinical trials. However, most patients experience a decline in islet graft function in one to three years due to immune rejection. Although the mechanisms of immune cells, including macrophages, dendritic cells (DCs), neutrophils, natural killer cells (NKs), B cells, and T cells, that mediate immune rejection have been investigated, the overall characteristics of immune infiltrates in islet allografts and syngeneic grafts remain unclear. Single-cell RNA sequencing (scRNA-seq) has provided us with new opportunities to study the complexity of the immune microenvironment in islet transplants. In the present study, we used scRNA-seq to comprehensively analyze the immune heterogeneity in the mouse model of islet transplantation. Our data revealed T lymphocytes and myeloid cells as the main immune components of grafts 7 days post-islet transplantation, especially in allografts. Moreover, our results indicated that allogeneic islet cells were transformed into antigen-presenting cell-like cells with highly expressed MHC class I molecules and genes involved in MHC class I-mediated antigen presentation. This transformation may dramatically facilitate the interaction with cytotoxic CD8 + T cells and promote the destruction of islet allografts. Our study provides insight into the transcriptomics and diverse microenvironment of islet grafts and their impacts on immune rejection.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-9-14)
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-9-14)
    Abstract: Age-related macular degeneration (AMD) causes central vision impairment with increased incidence. In the pathogenesis of AMD, reactive oxygen species (ROS) are associated with RPE cell apoptosis. H 2 O 2 is an oxidative toxicant and is used to establish the AMD in vitro model. However, the mechanisms of ROS in H 2 O 2 -induced AMD are still unclear. Fullerenol, a promising antioxidant of nanomaterials, protects RPE cells from ROS attack. In addition to working as a scavenger, little is known about the antioxidant mechanism of fullerenol in RPE cells. In this study, transcriptome sequencing was performed to examine the global changes in mRNA transcripts induced by H 2 O 2 in human ARPE-19 cells. Moreover, we comprehensively investigated the protective effects of fullerenol against H 2 O 2 -induced oxidative injury by RNA sequencing. Gene Ontology enrichment analysis showed that those pathways related to the release of positive regulation of DNA-templated transcription and negative regulation of apoptotic process were affected. Finally, we found that 12 hub genes were related to the oxidative-protection function of fullerenol. In summary, H 2 O 2 affected these hub genes and signaling pathways to regulate the senescence of RPE cells. Moreover, fullerenol is a potent nanomaterial that protects the RPE and would be a promising approach for AMD prevention.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Endocrinology Vol. 13 ( 2023-1-4)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 13 ( 2023-1-4)
    Abstract: Previous experimental studies have reported an association between microcystin-LR (MC-LR) and glucose homeostasis, but whether exposure to MC-LR is a risk factor for the pathogenesis of gestational diabetes mellitus (GDM) requires further epidemiological study. This study aims to explore the effects of MC-LR on GDM. Methods A prospective nested case-control study was performed in the Hunan Provincial Maternal and Child Health Hospital (HPMCHH) in South China. A total of 119 patients with GDM and 238 controls were enrolled in the study. The two independent samples t-test, or chi-square test was used to compare the difference between the GDM group and the non-GDM group. Binary logistic regression was used to obtain odds ratios (ORs) by controlling for confounders. Results The cumulative incidence of GDM in our sample was 13.7%. The detection rate of MC-LR in the GDM group were significantly higher than those in the control group (44.2% vs. 29.4%; p =0.007). Our results show that an elevated serum MC-LR level in the first trimester of pregnancy was related to an increased risk of GDM (OR: 1.924; 95% CI: 1.092-3.391; p & lt;0.05). When stratified by age, educational level, parity, and passive smoking, significantly relationships were observed among those aged & gt;30 years, lower income, higher education, none passive smoking, and more likely to be multiparous. Conclusions Our data reveals that serum MC-LR level in the first trimester is independently associated with GDM.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2592084-4
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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cell and Developmental Biology Vol. 9 ( 2022-1-4)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 9 ( 2022-1-4)
    Abstract: Abnormal activation of protein kinases and phosphatases is implicated in various tumorigenesis, including hepatocellular carcinoma (HCC). Advanced HCC patients are treated with systemic therapy, including tyrosine kinase inhibitors, which extend overall survival. Investigation of the underlying mechanism of protein kinase signaling will help to improve the efficacy of HCC therapy. Combining single-cell RNA sequencing data and TCGA RNA-seq data, we profiled the protein kinases, phosphatases, and other phosphorylation-related genes (PRGs) of HCC patients in this study. We found nine protein kinases and PRGs with high expression levels that were mainly detected in HCC cancer stem cells, including POLR2G , PPP2R1A , POLR2L , PRC1 , ITBG1BP1 , MARCKSL1 , EZH2 , DTYMK, and AURKA. Survival analysis with the TCGA dataset showed that these genes were associated with poor prognosis of HCC patients. Further correlation analysis showed that these genes were involved in cell cycle-related pathways that may contribute to the development of HCC. Among them, AURKA and EZH2 were identified as two hub genes by Ingenuity Pathway Analysis. Treatment with an AURKA inhibitor (alisertib) and an EZH2 inhibitor (gambogenic) inhibited HCC cell proliferation, migration, and invasion. We also found that both AURKA and EZH2 were highly expressed in TP53 -mutant HCC samples. Our comprehensive analysis of PRGs contributes to illustrating the mechanisms underlying HCC progression and identifying potential therapeutic targets for future clinical trials.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2737824-X
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  • 6
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-4-1)
    Abstract: Pig islet xenotransplantation is a potential treatment for patients with type 1 diabetes. Current efforts are focused on identifying the optimal pig islet source and overcoming the immunological barrier. The optimal age of the pig donors remains controversial since both adult and neonatal pig islets have advantages. Isolation of adult islets using GMP grade collagenase has significantly improved the quantity and quality of adult islets, but neonatal islets can be isolated at a much lower cost. Certain culture media and coculture with mesenchymal stromal cells facilitate neonatal islet maturation and function. Genetic modification in pigs affords a promising strategy to prevent rejection. Deletion of expression of the three known carbohydrate xenoantigens (Gal, Neu5Gc, Sda) will certainly be beneficial in pig organ transplantation in humans, but this is not yet proven in islet transplantation, though the challenge of the ‘4th xenoantigen’ may prove problematic in nonhuman primate models. Blockade of the CD40/CD154 costimulation pathway leads to long-term islet graft survival (of up to 965 days). Anti-CD40mAbs have already been applied in phase II clinical trials of islet allo transplantation. Fc region-modified anti-CD154mAbs successfully prevent the thrombotic complications reported previously. In this review, we discuss (I) the optimal age of the islet-source pig, (ii) progress in genetic modification of pigs, (iii) the immunosuppressive regimen for pig islet xenotransplantation, and (iv) the reduction in the instant blood-mediated inflammatory reaction.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Cell and Developmental Biology Vol. 9 ( 2021-12-13)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 9 ( 2021-12-13)
    Abstract: Gastric cancer (GC) is a malignant disease of the digestive tract and a life-threatening disease worldwide. Ferroptosis, an iron-dependent cell death caused by lipid peroxidation, is reported to be highly correlated with gastric tumorigenesis and immune cell activity. However, the underlying relationship between ferroptosis and the tumor microenvironment in GC and potential intervention strategies have not been unveiled. In this study, we profiled the transcriptome and prognosis data of ferroptosis-related genes (FRGs) in GC samples of the TCGA-STAD dataset. The infiltrating immune cells in GC were estimated using the CIBERSORT and XCELL algorithms. We found that the high expression of the hub FRGs ( MYB , PSAT1 , TP53 , and LONP1 ) was positively correlated with poor overall survival in GC patients. The results were validated in an external GC cohort (GSE62254). Further immune cell infiltration analysis revealed that CD4 + T cells were the major infiltrated cells in the tumor microenvironment of GC. Moreover, the hub FRGs were significantly positively correlated with activated CD4 + T cell infiltration, especially Th cells. The gene features in the high-FRG score group were enriched in cell division, DNA repair, protein folding, T cell receptor, Wnt and NIK/NF-kappaB signaling pathways, indicating that the hub FRGs may mediate CD4 + T cell activation by these pathways. In addition, an upstream transcriptional regulation network of the hub FRGs by lncRNAs was also developed. Three lncRNAs ( A2M-AS1 , C2orf27A , and ZNF667-AS1 ) were identified to be related to the expression of the hub FRGs. Collectively, these results showed that lncRNA A2M-AS1 , C2orf27A , and ZNF667-AS1 may target the hub FRGs and impair CD4 + T cell activation, which finally leads to poor prognosis of GC. Effective interventions for the above lncRNAs and the hub FRGs can help promote CD4 + T cell activation in GC patients and improve the efficacy of immunotherapy. These findings provide a novel idea of GC immunotherapy and hold promise for future clinical application.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2737824-X
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Cellular and Infection Microbiology Vol. 11 ( 2021-8-19)
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 11 ( 2021-8-19)
    Abstract: Proline-glutamic acid (PE)- and proline-proline-glutamic acid (PPE)-containing proteins are exclusive to Mycobacterium tuberculosis ( MTB ), the leading cause of tuberculosis (TB). In this study, we performed global transcriptome sequencing (RNA-Seq) on PPE57-stimulated peripheral blood mononuclear cells (PBMCs) and control samples to quantitatively measure the expression level of key transcripts of interest. A total of 1367 differentially expressed genes (DEGs) were observed in response to a 6 h exposure to PPE57, with 685 being up-regulated and 682 down-regulated. Immune-related gene functions and pathways associated with these genes were evaluated, revealing that the type I IFN signaling pathway was the most significantly enriched pathway in our RNA-seq dataset, with 14 DEGs identified therein including ISG15, MX2, IRF9, IFIT3, IFIT2, OAS3, IFIT1, IFI6, OAS2, OASL, RSAD2, OAS1, IRF7 , and MX1 . These PPE57-related transcriptomic profiles have implications for a better understanding of host global immune mechanisms underlying MTB infection outcomes. However, more studies regarding these DEGs and type I IFN signaling in this infectious context are necessary to more fully clarify the underlying mechanisms that arise in response to PPE57 during MTB infection.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2619676-1
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  • 9
    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 10 ( 2023-6-8)
    Abstract: Chinese college students used to eat in student canteens, making dietary consumption outside the cafeterias the main reason for the difference in sodium intake. This study aims to develop and validate a food frequency questionnaire (Sodium-FFQ) targeting dietary sodium intake outside the canteens among undergraduates in China. Methods This cross-sectional study included 124 and 81 college students from comprehensive universities in the development and validation stage. A 24 h dietary recall and a food frequency questionnaire were used to develop the Sodium-FFQ. Food items were selected according to the foods that contributed more to the total sodium intake. Test–retest correlation coefficients with an interval of 14 days were employed to evaluate reproducibility. Validity was assessed against a single 24 h urine collection and a 3-day dietary record using correlation coefficients, Bland–Altman analyses, and cross-classification analysis of Kappa coefficients. Results The Sodium-FFQ consists of 12 groups of foods with 48 items. The Spearman correlation coefficient of test–retest on sodium intake was 0.654 ( p   & lt; 0.05), and that between the Sodium-FFQ, 3 × 24 h dietary record, and 24-h urinary sodium were 0.393 ( p   & lt; 0.05) and 0.342 ( p   & lt; 0.05), respectively. The Sodium-FFQ was correlated to 24 h urinary sodium-to-potassium ratio, with a Spearman coefficient of 0.370 ( p   & lt; 0.05). The classification agreement of the Sodium-FFQ and 24 h urinary sodium was 68.4%, and the Kappa coefficient was 0.371 ( p   & lt; 0.001). Conclusion The Sodium-FFQ developed in this study presented an acceptable reproducibility, validity, and classification agreement. It indicates that the Sodium-FFQ could be a potential tool for promoting sodium restriction in college students.
    Type of Medium: Online Resource
    ISSN: 2296-861X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2776676-7
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  • 10
    In: Frontiers in Psychology, Frontiers Media SA, Vol. 14 ( 2023-7-14)
    Abstract: The morbidity of thyroid cancer has been increasing in the last decades all over the world. In addition to the more sensitive thyroid nodule screening technology, several social and environmental factors might represent credible candidates for this increase. They include psychological stress, lifestyle-associated risk factors, nutritional deficiencies, and environmental pollutants. Foremost, psychological stress had gained high interest as a possible promoter and a modifiable risk factor for thyroid nodules in recent years. The present study was to investigate the clinical characteristics and psychological status of the population during the peak of coronavirus disease 2019 (COVID-19) and assessed the association of psychosocial determinants and the ultrasonic characteristics of thyroid nodules. Methods In this cross-sectional study, 490 adult subjects who had received at least two doses of COVID-19 vaccine and were not infected with COVID-19, and did not know whether they had thyroid nodules, received thyroid color ultrasound examination and psychological questionnaire survey. Depression, anxiety, and stress were assessed using Depression Anxiety Stress Scales-21 (DASS-21). Sleep quality was rated using the Pittsburgh sleep quality index (PQSI). The characteristics of 243 subjects with thyroid nodules were described and recorded in detail by thyroid color ultrasound, and the correlations between anxiety, depression, sleep quality, clinical indicators, and thyroid nodule ultrasound characteristics were analyzed. Associations between psychological status (mutually adjusted predictors) and ultrasonic characteristics of thyroid nodules (outcome) were modeled using binary logistic regression controlling for sex, age, BMI, TSH, FT3, and FT4. Results Depression was positively correlated with thyroid hypoechoic nodule (OR = 3.720, 95%CI 1.615–8.570), microcalcification of thyroid nodule (OR = 3.638, 95%CI 1.476–8.966), the aspect ratio of thyroid nodule & gt;1 (OR = 3.860, 95%CI 1.052–14.161), the unclear boundary of thyroid nodule (OR = 4.254, 95%CI 1.359–13.312), and the irregular edge of thyroid nodule (OR = 4.134, 95%CI 1.810–9.439). Anxiety was positively correlated with microcalcification of thyroid nodules (OR = 4.319, 95%CI 1.487–11.409). Stress was positively correlated with thyroid hypoechoic nodules (OR = 4.319, 95%CI 1.487–11.409), microcalcification of thyroid nodules (OR = 2.724, 95%CI 1.038–7.151), and the irregular edge of thyroid nodules (OR = 2.478, 95%CI 1.077–5.705). Conclusion This study demonstrates that depression, anxiety, and stress were associated with the morbidity of thyroid nodules and thyroid ultrasound characteristics. During COVID-19, people’s negative emotions increased significantly compared to before. Negative emotions might be harmful to thyroid health. Therefore, during periods of high stress, strategies to prevent psychological problems should be implemented to improve thyroid health.
    Type of Medium: Online Resource
    ISSN: 1664-1078
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2563826-9
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