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  • Frontiers Media SA  (47)
  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-4-28)
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-4-28)
    Abstract: Patients with endometrial cancer (EC) combined with metabolic syndrome (MetS) have a worse prognosis than those without MetS. This study aimed to investigate whether partial metabolic disorder significantly influenced early-stage endometrioid EC (EEC) survival and searched for a more efficient method to evaluate metabolic status. Methods This is a nationwide, multicenter cohort study that included 998 patients with primary early-stage EEC from 2001 to 2018. Patients were divided into different metabolic groups based on the diagnostic criteria of the Chinese Medical Association (CDC). The progression-free survival (PFS) time was compared between various metabolic status. Meanwhile, we established an EC Prognostic-Related Metabolic Score (ECPRM Score) to explore the association of the severity of metabolic status and early-stage EEC PFS. A nomogram was established for predicting PFS, which was externally validated in a testing set that includes 296 patients. Results A partial metabolic disorder, as well as MetS, was an independent risk factor of poor survival of patients with early-stage EEC [hazard ratio (HR) = 7.6, 95% CI = 1.01–57.5, p & lt; 0.05]. A high ECPRM Score was associated with lower PFS (HR = 2.1, 95% CI = 1.05–4.0, p & lt; 0.001). The nomogram, in which the ECPRM Score contributed most to the prognosis, exhibited excellent discrimination of survival supported by the internal and external validations. In addition, the calibration curve supports its robust predicting ability. Conclusion Even though they do not meet the criteria of MetS, partial metabolic disorders were also associated with adverse outcomes in early-stage EEC. The ECPRM Score is beneficial for clinicians to evaluate the severity of metabolic abnormalities and guide patients to ameliorate the poor prognosis of metabolic disorders.
    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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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-4-14)
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-4-14)
    Abstract: The aim of the present study was to determine overall survival (OS) and risk factors associated with early recurrence in patients with FIGO I–II stage endometrial carcinoma (EC). Methods Clinical features were retrospectively extracted from the database of China Endometrial Cancer Consortium from January 2000 to December 2019. A total of 2,974 patients with Federation International of Gynecology and Obstetrics (FIGO) I–II stage endometrial cancer were included. Kaplan-Meier survival analysis was used to assess OS and disease-specific survival. Cox proportional hazard model and Fine-Gray model were used to determine the factors related to OS. Binary logistic regression model was used to determine independent predictors of early relapse patients. Results Of these 2,974 ECs, 189 patients were confirmed to have relapse. The 5-year OS was significantly different between the recurrence and non-recurrence patients ( p & lt; 0.001). Three quarters of the relapse patients were reported in 36 months. The 5-year OS for early recurrence patients was shorter than late recurrence [relapse beyond 36 months, p & lt; 0.001]. The grade 3 [odds ratio (OR) = 1.55, 95%CI 1.17–2.05, p = 0.002], lymphatic vascular infiltration (LVSI; OR = 3.36; 95%CI 1.50–7.54, p = 0.003), and myometrial infiltration (OR = 2.07, 95%CI 1.17—3.65, p = 0.012) were independent risk factors of early relapse. The protective factor of that is progesterone receptor (PR)-positive (OR = 0.50, 95%CI 0.27–0.92, p = 0.02). Bilateral ovariectomy could reduce recurrence risk rate (OR = 0.26, 95%CI 0.14–0.51, p & lt; 0.001). Conclusion The OS of early relapse EC is worse. Grade 3, LVSI, and myometrial infiltration are independent risk factors for early relapse EC. In addition, the protective factor is PR-positive for those people and bilateral salpingo-oophorectomy could reduce the risk of recurrence.
    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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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Cell and Developmental Biology Vol. 8 ( 2021-1-8)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 8 ( 2021-1-8)
    Abstract: Cryptophthalmos is characterized by congenital ocular dysplasia with eyelid malformation. The pathogenicity of mutations in genes encoding components of the FRAS1/FREM protein complex is well established, but the underlying pathomechanisms of this disease are still unclear. In the previous study, we generated mice carrying Frem2 R725X/R2156W compound heterozygous mutations using CRISPR/Cas9 and showed that these mice recapitulated the human cryptophthalmos phenotype. Methods In this study, we tracked changes in the metabolic profile of embryos and expression of metabolism-related genes in Frem2 mutant mice on E13.5 compared with wild-type mice. RNA sequencing (RNA-seq) was utilized to decipher the differentiated expression of genes associated with metabolism. Untargeted metabolomics and targeted metabolomics analyses were performed to detect and verify the shifts in the composition of the embryonic metabolome. Results Differentially expressed genes participating in amino acid metabolism and energy metabolism were observed by RNA-seq. Transcriptomic analysis suggests that 821 (39.89%) up-regulated genes and 320 (32.99%) down-regulated genes were involved in the metabolic process in the enriched GO terms. A total of 92 significantly different metabolites were identified including creatine, guanosine 5′-monophosphate, cytosine, cytidine 5′-monophosphate, adenine, and L -serine. Interestingly, major shifts related to ATP binding cassette transporters (ABC transporters) and the biosynthesis of amino acids in the composition of the embryonic metabolome were observed by KEGG metabolic analysis, indicating that these pathways could also be involved in the pathogenesis of cryptophthalmos. Conclusion We demonstrate that Frem2 mutant fetal mice have increased susceptibility to the disruption of eye morphogenesis in association with distinct transcriptomic and metabolomic signatures. Our findings suggest that the metabolomic signature established before birth may play a role in mediating cryptophthalmos in Frem2 mutant mice, which may have important implications for the pathogenesis of cryptophthalmos.
    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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  • 4
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2021-10-21)
    Abstract: Objective: To systematically evaluate lymph node metastasis (LNM) patterns in patients with endometrial cancer (EC) who underwent complete surgical staging, which included systematic pelvic and para-aortic lymphadenectomy. Methods: Four thousand and one patients who underwent complete surgical staging including systematic pelvic and para-aortic lymphadenectomy for EC were enrolled from 30 centers in China from 2001 to 2019. We systematically displayed the clinical and prognostic characteristics of patients with various LNM patterns, especially the PLN-PAN+ [para-aortic lymph node (PAN) metastasis without pelvic lymph node (PLN) metastasis]. The efficacy of PAN+ (para-aortic lymph node metastasis) prediction with clinical and pathological features was evaluated. Results: Overall, 431 of the 4,001 patients (10.8%) showed definite LNM according to pathological diagnosis. The PAN+ showed the highest frequency (6.6%) among all metastatic sites. One hundred fourteen cases (26.5%) were PLN-PAN+ (PAN metastasis without PLN metastasis), 167 cases (38.7%) showed PLN+PAN-(PLN metastasis without PAN metastasis), and 150 cases (34.8%) showed metastasis to both regions (PLN+PAN+). There was also 1.9% (51/2,660) of low-risk patients who had PLN-PAN+. There are no statistical differences in relapse-free survival (RFS) and disease-specific survival (DSS) among PLN+PAN-, PLN-PAN+, and PLN+PAN+. The sensitivity of gross PLNs, gross PANs, and lymphovascular space involvement (LVSI) to predict PAN+ was 53.8 [95% confidence interval (CI): 47.6–59.9], 74.2 95% CI: 65.6–81.4), and 45.8% (95% CI: 38.7–53.2), respectively. Conclusion: Over one-fourth of EC patients with LMN metastases were PLN-PAN+. PLN-PAN+ shares approximate survival outcomes (RFS and DSS) with other LNM patterns. No effective clinical methods were achieved for predicting PAN+. Thus, PLN-PAN+ is a non-negligible LNM pattern that cannot be underestimated in EC, even in low-risk patients.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2775999-4
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  • 5
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 11 ( 2023-8-28)
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2719493-0
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  • 6
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 14 ( 2020-10-2)
    Type of Medium: Online Resource
    ISSN: 1662-453X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2411902-7
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Bioengineering and Biotechnology Vol. 11 ( 2023-6-29)
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 11 ( 2023-6-29)
    Abstract: Single-cell genomic whole genome amplification (WGA) is a crucial step in single-cell sequencing, yet its low amplification efficiency, incomplete and uneven genome amplification still hinder the throughput and efficiency of single-cell sequencing workflows. Here we introduce a process called Improved Single-cell Genome Amplification (iSGA), in which the whole single-cell sequencing cycle is completed in a high-efficient and high-coverage manner, through phi29 DNA polymerase engineering and process engineering. By establishing a disulfide bond of F137C-A377C, the amplification ability of the enzyme was improved to that of single-cell. By further protein engineering and process engineering, a supreme enzyme named HotJa Phi29 DNA Polymerase was developed and showed significantly better coverage (99.75%) at a higher temperature (40°C). High single-cell genome amplification ability and high coverage (93.59%) were also achieved for commercial probiotic samples. iSGA is more efficient and robust than the wild-type phi29 DNA polymerase, and it is 2.03-fold more efficient and 10.89-fold cheaper than the commercial Thermo Scientific EquiPhi29 DNA Polymerase. These advantages promise its broad applications in large-scale single-cell sequencing.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2719493-0
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Endocrinology Vol. 12 ( 2021-9-9)
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 12 ( 2021-9-9)
    Abstract: It has been demonstrated that activated islet stellate cells (ISCs) play a critical role in islet fibrogenesis and significantly contribute to the progression of type 2 diabetes mellitus. However, the key molecules responsible for ISCs activation have not yet been determined. This study aimed to identify the potential key genes involved in diabetes-induced activation of ISCs. Method Stellate cells were isolated from three 10-week-old healthy male Wistar rats and three Goto-Kakizaki (GK) rats. Cells from each rat were primary cultured under the same condition. A Genome-wide transcriptional sequence of stellate cells was generated using the Hiseq3000 platform. The identified differentially expressed genes were validated using quantitative real-time PCR and western blotting in GK rats, high fat diet (HFD) rats, and their controls. Results A total of 204 differentially expressed genes (DEGs) between GK. ISCs and Wistar ISCs (W.ISCs) were identified, accounting for 0.58% of all the 35,362 genes detected. After the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses, the mRNA levels of these genes were further confirmed by real-time PCR in cultured ISCs. We then selected Fos , Pdpn , Bad as the potential key genes for diabetes-induced activation of ISCs. Finally, we confirmed the protein expression levels of FOS, podoplanin, and Bad by western blotting and immunofluorescence in GK rats, HFD rats, and their controls. The results showed that the expression level of FOS was significantly decreased, while podoplanin and Bad were significantly increased in GK.ISCs and HFD rats compared with controls, which were consistent with the expression of α-smooth muscle actin. Conclusions A total of 204 DEGs were found between the GK.ISCs and W.ISCs. After validating the expression of potential key genes from GK rats and HFD rats, Fos , Pdpn , and Bad might be potential key genes involved in diabetes-induced activation of ISCs.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2592084-4
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  • 9
    In: Frontiers in Behavioral Neuroscience, Frontiers Media SA, Vol. 13 ( 2019-6-25)
    Type of Medium: Online Resource
    ISSN: 1662-5153
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2452960-6
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  • 10
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-9-2)
    Abstract: Radiotherapy plays an important effect on the standard therapy of esophageal squamous cell carcinoma (ESCC). However, the efficacy of the therapy is limited and a few patients do not achieve satisfactory treatment results due to the existence of radiation resistance. Therefore, it is necessary to identify the potential predictive biomarkers and treatment targets for ESCC. Methods We performed the whole-exome sequencing to determine the germline and somatic mutations in ESCC. Functional enrichment and pathway-based protein-protein interaction analyses were used to ascertain potential regulatory networks. Cell survival and cell death after treatment with radiotherapy were determined by CCK-8 and LDH release assays in ESCC cells. The correlations of NOTCH1 and tumor immune infiltration were also analyzed in ESCC. Results Our results showed that 344 somatic and 65 germline differentially mutated genes were detected to be radiosensitivity-related loci. The tumor mutational burdens (TMB) or microsatellite instability (MSI) were not significantly correlated with the response to radiotherapy in ESCC patients. Pathway-based protein-protein interaction analyses implied several hub genes with most nodes (such as PIK3CA, NOTCH1, STAT3 and KDR). The in vitro studies showed that the knockdown of NOTCH1 inhibited cell survival and rendered more cell death after the treatment with radiotherapy in ESCC cells, while NOTCH1 overexpression had the opposite effects. Moreover, NOTCH1, frequently up-regulated in ESCC, was negatively correlated with activated B cell and immature dendritic cell in ESCC. High expression of NOTCH1 was accompanied with the low levels of some immunotherapy-related cells, including CD8(+) T cells and NK cells. Conclusions These results indicate the differences of the germline mutations and somatic mutations between the radiosensitive and radioresistence groups in ESCC and imply that NOTCH1 plays important roles in regulating the radiosensitivity of ESCC. The findings might provide the biomarkers and potential treatment targets for improving the sensitivity to radiotherapy in ESCC.
    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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