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  • Frontiers Media SA  (48)
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  • Frontiers Media SA  (48)
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  • 1
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-5-29)
    Abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide, mostly as a result of the absence of early detection and specific treatment solutions. Consequently, identifying mutational profiles and molecular biomarkers is essential for increasing the viability of precision therapy for pancreatic cancer. Methods We collected blood and tumor tissue samples from 47 Chinese pancreatic cancer patients and used whole-exome sequencing (WES) to evaluate the genetic landscape. Results Our results showed the most frequently somatic alteration genes were KRAS (74.5%), TP53(51.1%), SMAD4 (17%), ARID1A (12.8%), CDKN2A (12.8%), TENM4 (10.6%), TTN (8.5%), RNF43(8.5%), FLG (8.5%) and GAS6 (6.4%) in Chinese PDAC patients. We also found that three deleterious germline mutations (ATM c.4852C & gt;T/p. R1618*, WRN c.1105C & gt;T/p. R369*, PALB2 c.2760dupA/p. Q921Tfs*7) and two novel fusions (BRCA1-RPRML, MIR943 (intergenic)-FGFR3). When compared to the Cancer Genome Atlas (TCGA) database, there is a greater mutation frequency of TENM4 (10.6% vs. 1.6%, p = 0.01), GAS6(6.4% vs. 0.5%, p = 0.035), MMP17(6.4% vs. 0.5%, p = 0.035), ITM2B (6.4% vs. 0.5%, p = 0.035) and USP7 (6.4% vs. 0.5%, p = 0.035) as well as a reduced mutation frequency of SMAD4 (17.0% vs. 31.5%, p = 0.075) and CDKN2A (12.8% vs. 47.3%, p & lt; 0.001) were observed in the Chinese cohort. Among the 41 individuals examined for programmed cell death ligand 1(PD-L1) expression, 15 (36.6%) had positive PD-L1 expression. The median tumor mutational burden (TMB) was found to be 12muts (range, 0124). The TMB index was higher in patients with mutant-type KRAS MUT/TP53 MUT ( p & lt; 0.001), CDKN2A ( p = 0.547), or SMAD4 ( p = 0.064) compared to patients with wild-type KRAS/TP53, CDKN2A, or SMAD4. Conclusions We exhibited real-world genetic traits and new alterations in Chinese individuals with cancer of the pancreas, which might have interesting implications for future individualized therapy and medication development.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Pharmacology Vol. 14 ( 2023-2-16)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 14 ( 2023-2-16)
    Abstract: Objective: To examine the kinetics of B cell subsets and activation markers in the early stage of belimumab treatment and their correction with treatment response. Methods: We enrolled 27 systemic lupus erythematosus (SLE) patients receiving 6 months belimumab treatment. Flow cytometry was used to test their B cell subsets and activation markers (including CD40, CD80, CD95, CD21 low , CD22, p-SYK and p-AKT). Results: During belimumab treatment, SLEDAI-2K declined, the proportions of CD19 + B cells and naïve B cells decreased, whereas the switched memory B cells and non-switched B cells increased. The larger variations of the B cell subsets and the activation markers were in the first 1 month than the other later time frames. The ratio of p-SYK/p-AKT on non-switched B cell at 1 month was associated with the SLEDAI-2K decline rate in the 6 months of belimumab treatment. Conclusion: B cell hyperactivity was rapidly inhibited in the early stage of belimumab treatment, and the ratio of p-SYK/p-AKT may predict SLEDAI-2K decline. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT04893161?term=NCT04893161 & amp;draw=2 & amp;rank=1 ; identifier: NCT04893161.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-5-26)
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-5-26)
    Abstract: Recent studies highlighted that CD8+ T cells are necessary for restraining reservoir in HIV-1-infected individuals who undergo antiretroviral therapy (ART), whereas the underlying cellular and molecular mechanisms remain largely unknown. Here, we enrolled 60 virologically suppressed HIV-1-infected individuals, to assess the correlations of the effector molecules and phenotypic subsets of CD8+ T cells with HIV-1 DNA and cell-associated unspliced RNA (CA usRNA). We found that the levels of HIV-1 DNA and usRNA correlated positively with the percentage of CCL4+CCL5- CD8+ central memory cells (T CM ) while negatively with CCL4-CCL5+ CD8+ terminally differentiated effector memory cells (T EMRA ). Moreover, a virtual memory CD8+ T cell (T VM ) subset was enriched in CCL4-CCL5+ T EMRA cells and phenotypically distinctive from CCL4+ T CM subset, supported by single-cell RNA-Seq data. Specifically, T VM cells showed superior cytotoxicity potentially driven by T-bet and RUNX3, while CCL4+ T CM subset displayed a suppressive phenotype dominated by JUNB and CREM. In viral inhibition assays, T VM cells inhibited HIV-1 reactivation more effectively than non-T VM CD8+ T cells, which was dependent on CCL5 secretion. Our study highlights CCL5-secreting T VM cells subset as a potential determinant of HIV-1 reservoir size. This might be helpful to design CD8+ T cell-based therapeutic strategies for cure of the disease.
    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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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Cell and Developmental Biology Vol. 9 ( 2021-8-17)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 9 ( 2021-8-17)
    Abstract: Thrombocytopenia is closely linked with hemorrhagic diseases, for which induction of thrombopoiesis shows promise as an effective treatment. Polyphenols widely exist in plants and manifest antioxidation and antitumour activities. In this study, we investigated the thrombopoietic effect and mechanism of 3,3′,4′-trimethylellagic acid (TMEA, a polyphenol in Sanguisorba officinalis L.) using in silico prediction and experimental validation. A KEGG analysis indicated that PI3K/Akt signalling functioned as a crucial pathway. Furthermore, the virtual molecular docking results showed high-affinity binding (a docking score of 6.65) between TMEA and mTOR, suggesting that TMEA might target the mTOR protein to modulate signalling activity. After isolation of TMEA, in vitro and in vivo validation revealed that this compound could promote megakaryocyte differentiation/maturation and platelet formation. In addition, it enhanced the phosphorylation of PI3K, Akt, mTOR, and P70S6K and increased the expression of GATA-1 and NF-E2, which confirmed the mechanism prediction. In conclusion, our findings are the first to demonstrate that TMEA may provide a novel therapeutic strategy that relies on the PI3K/Akt/mTOR pathway to facilitate megakaryocyte differentiation and platelet production.
    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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  • 5
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 10 ( 2021-1-29)
    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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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2020
    In:  Frontiers in Oncology Vol. 10 ( 2020-12-2)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 10 ( 2020-12-2)
    Abstract: Many primary tumors have insufficient supply of molecular oxygen, called hypoxia. Hypoxia is one of the leading characteristics of solid tumors resulting in a higher risk of local failure and distant metastasis. It is quite necessary to investigate the hypoxia associated molecular hallmarks in breast cancer. Materials and Methods According to the published studies, we selected 13 hypoxia related gene expression signature to define the hypoxia status of breast cancer using ConsensusClusterPlus package based on the data from The Cancer Genome Atlas (TCGA). Subsequently, we characterized the infiltration of 24 immune cell types under different hypoxic conditions. Furthermore, the differentially expressed hypoxia associated microRNAs, mRNAs and related signaling pathways were analyzed and depicted. On this basis, a series of prognostic markers related to hypoxia were identified and ceRNA co-expression networks were constructed. Results Two subgroups (cluster1 and cluster2) were identified and the 13 hypoxia related gene signature were all up-regulated in cluster1. Thus, we defined the cluster1 as “hypoxic subgroup” compared with cluster2. The infiltration of CD8+ T cell and CD4+ T cell were lower in cluster1 while the nTreg cell and iTreg cell were higher, indicating that there was immunosuppressive status in cluster1. We observed widespread hypoxia-associated dysregulation of microRNAs and mRNAs. Next, a risk signature for predicting prognosis of breast cancer patients was established based on 12 dysregulated hypoxia associated prognostic genes. Two microRNAs, hsa-miR-210-3p and hsa-miR-190b, with the most significant absolute logFC value were related to unfavorable and better prognosis, respectively. Several long non-coding RNAs were predicted to be microRNA targets and positively correlated with two selected mRNAs, CPEB2 and BCL11A. Predictions based on the LINC00899/PSMG3-AS1/PAXIP1-AS1- hsa-miR-210-3p-CPEB2 and SNHG16- hsa-miR-190b-BCL11A ceRNA regulation networks indicated that the two genes might act as tumor suppressor and oncogene, respectively. Conclusion Hypoxia plays an important role in the initiation and progression of breast cancer. Our research provides potential mechanisms into molecular-level understanding of tumor hypoxia.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2649216-7
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2021
    In:  Frontiers in Psychology Vol. 12 ( 2021-10-21)
    In: Frontiers in Psychology, Frontiers Media SA, Vol. 12 ( 2021-10-21)
    Abstract: Previous studies have found that promoting multiple identities can improve children’s creative performance (divergent thinking). The present study employed a priming paradigm to design two experiments and investigate whether promoting a sense of multiple identities in middle school students could enhance their divergent thinking, a key component of creativity. In Experiment 1, 77 junior high school students were divided into multiple identities and physical trait condition groups. They were instructed to think about a child with multiple identities or physical traits. The results showed that there were no differences in divergent thinking (DT) scores between the two groups. In Experiment 2, we modified the priming method by asking participants to think about and write a description of the various identities or physical traits and employed a subjective top-scoring method to make up for shortcomings in the traditional scoring method when applied to originality. The results still showed no significant difference in scores between the identity and physical trait groups. Thus, the results of this study contradict those of previous research, which found that the identity group demonstrated significantly higher scores on a creativity test than did those in the physical trait group. Several potential factors affect this outcome, but it seems that priming to enhance divergent thinking is not particularly effective. Thus, the social priming effect should be pursued with caution regarding both replicability and generalizability.
    Type of Medium: Online Resource
    ISSN: 1664-1078
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2563826-9
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  • 8
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-7-11)
    Abstract: To compare recurrence and survival outcomes between breast-conserving surgery (BCS) and mastectomy after neoadjuvant chemotherapy (NACT). Methods The data of 730 patients who underwent NACT between 2000 and 2014 were retrospectively reviewed. A total of 104 (14.2%) patients received BCS and 626 (85.8%) received mastectomy. Locoregional recurrence (LRR), distant metastases (DM), disease-free survival (DFS), breast cancer–specific survival (BCSS), and overall survival (OS) were analyzed using the Kaplan–Meier method. The impact of BCS versus mastectomy on outcomes was assessed by multivariate Cox models. Inverse probability of treatment weighting (IPTW) was used to balance covariates between the two groups. Results The median follow-up of BCS and mastectomy groups were 86.5 and 87.4 months, respectively. There were significant differences in distribution of most baseline characteristics between two groups. Compared with those who underwent mastectomy, the patients with BCS had similar 5-year LRR, DM, and DFS rates, but had significantly higher 5-year BCSS (98.9% vs. 90.4%, P = 0.005) and OS (98.9% vs. 90.1%, P = 0.003) rates. Multivariate analysis also showed that BCS significantly improved BCSS (HR = 0.27, 95% CI: 0.08-0.85, P = 0.025) and OS (HR = 0.25, 95% CI: 0.08-0.79, P = 0.018). After IPTW adjustment, the LRR, DM, DFS, BCSS and OS between two groups had no significant differences. Conclusions The recurrence and survival outcomes are comparable with BCS and mastectomy. Thus, BCS is a safe treatment option for selected breast cancer patients after NACT.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 9
    In: Frontiers in Behavioral Neuroscience, Frontiers Media SA, Vol. 16 ( 2022-9-8)
    Abstract: To screen and analyze the genetic mutations in the PPP1CB gene in a patient with Noonan syndrome with loose anagen hair-2 (NSLH2) in Yunnan Province, China and explore the possible molecular pathogenesis. Methods After obtaining informed consent, we collected the patient's medical history and carried out physical and laboratory examinations for the NSLH2 proband and the family members. Genomic DNA was extracted from the peripheral blood of all individuals. The coding regions including all pathogenic exons, parts of introns, and promoters of genes were sequenced by next-generation sequencing. Pathogenic mutations, which were detected in the probands and their parents, were verified by Sanger sequencing. Results The clinical manifestations of NSLH2 included prominent forehead, yellowish hair, slightly wide eye distance, sparse eyebrows, bilateral auricle deformity, reduced muscle tension, and cardiac and visual abnormalities. The proband carried a c.371A & gt;G mutation in exon 3 of PPP1CB , which is a missense mutation. This was a de novo mutation as the parents of the proband showed no mutation at this site. Conclusion In this study, we identified a novel mutation of PPP1CB , which enriched the mutation spectrum of the PPP1CB gene and provided a basis for the diagnosis of NSLH2.
    Type of Medium: Online Resource
    ISSN: 1662-5153
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2452960-6
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Genetics Vol. 13 ( 2022-10-4)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2022-10-4)
    Abstract: Long non-coding RNAs (lncRNAs) have been extensively studied as important regulators of tumor development in various cancers. Tumor protein 53 target gene 1 (TP53TG1) is a newly identified lncRNA in recent years, and several studies have shown that TP53TG1 may play oncogenic or anti-oncogenic roles in different cancers. Nevertheless, the role of TP53TG1 in the development of cervical cancer is unclear. In our study, pan-cancer analysis showed that high expression of TP53TG1 was significantly associated with a better prognosis. We then constructed a TP53TG1 overexpression model in HeLa cell line to explore its functions and molecular targets. We found that TP53TG1 overexpression significantly inhibited cell proliferation and induced apoptosis, demonstrating that TP53TG1 may be a novel anti-oncogenic factor in cervical cancer. Furthermore, overexpression of TP53TG1 could activate type I interferon signaling pathways and inhibit the expression of genes involved in DNA damage responses. Meanwhile, TP53TG1 could affect alternative splicing of genes involved in cell proliferation or apoptosis by regulating the expression of many RNA-binding protein genes. Competing endogenous RNA (ceRNA) network analysis demonstrated that TP53TG1 could act as the sponge of several miRNAs to regulate the expression level of target genes. In conclusion, our study highlights the essential role of lncRNA TP53TG1 in the development of cervical cancer and suggests the potential regulatory mechanisms.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606823-0
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