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  • 1
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    Table_1.DOCX
    Frontiers Media SA ; 2021
    In:  Frontiers in Cell and Developmental Biology Vol. 8 ( 2021-1-21)
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    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 8 ( 2021-1-21)
    Abstract: Despite the activation of autophagy may enable residual cancer cells to survive and allow tumor relapse, excessive activation of autophagy may eventually lead to cell death. However, the details of the association of autophagy with primary resistance in hepatocellular carcinoma (HCC) remain less clear. In this study, cohort analysis revealed that HCC patients receiving sorafenib with HBV had higher mortality risk. We found that high epidermal growth factor receptor (EGFR) expression and activity may be linked to HBV-induced sorafenib resistance. We further found that the resistance of EGFR-overexpressed liver cancer cells to sorafenib is associated with low activity of AMP-activated protein kinase (AMPK) and CCAAT/enhancer binding protein delta (CEBPD) as well as insufficient autophagic activation. In response to metformin, the AMPK/cAMP-response element binding protein (CREB) pathway contributes to CEBPD activation, which promotes autophagic cell death. Moreover, treatment with metformin can increase sorafenib sensitivity through AMPK activation in EGFR-overexpressed liver cancer cells. This study suggests that AMPK/CEBPD-activated autophagy could be a potent strategy for improving the efficacy of sorafenib in HCC patients.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    URL: Article
    URL: Article
    DOI: 10.3389/fcell.2020.596655
    DOI: 10.3389/fcell.2020.596655.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2737824-X
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  • 2
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    Table_1.DOCX
    Frontiers Media SA ; 2021
    In:  Frontiers in Cell and Developmental Biology Vol. 8 ( 2021-1-21)
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    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 8 ( 2021-1-21)
    Abstract: Despite the activation of autophagy may enable residual cancer cells to survive and allow tumor relapse, excessive activation of autophagy may eventually lead to cell death. However, the details of the association of autophagy with primary resistance in hepatocellular carcinoma (HCC) remain less clear. In this study, cohort analysis revealed that HCC patients receiving sorafenib with HBV had higher mortality risk. We found that high epidermal growth factor receptor (EGFR) expression and activity may be linked to HBV-induced sorafenib resistance. We further found that the resistance of EGFR-overexpressed liver cancer cells to sorafenib is associated with low activity of AMP-activated protein kinase (AMPK) and CCAAT/enhancer binding protein delta (CEBPD) as well as insufficient autophagic activation. In response to metformin, the AMPK/cAMP-response element binding protein (CREB) pathway contributes to CEBPD activation, which promotes autophagic cell death. Moreover, treatment with metformin can increase sorafenib sensitivity through AMPK activation in EGFR-overexpressed liver cancer cells. This study suggests that AMPK/CEBPD-activated autophagy could be a potent strategy for improving the efficacy of sorafenib in HCC patients.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    URL: Article
    URL: Article
    DOI: 10.3389/fcell.2021.596655
    DOI: 10.3389/fcell.2021.596655.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 3
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    Taiwan Society of Colon and Rectal Surgeons Consensus on mCRC Treatment
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-11-15)
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    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-11-15)
    Abstract: Therapeutic options for metastatic CRC (mCRC) have changed significantly in recent years, greatly increasing the complexity of therapeutic decision-making. Although oncology guidelines have helped improve the care process, guidelines may also limit the flexibility to individualize in-clinic decision-making. This consensus paper addresses specific gaps in the current international guidelines to assist Taiwanese colon and rectal experts make specific therapeutic choices. Over 3 years and three meetings with selected experts on “real-world” Taiwanese practice patterns for mCRC, consensus was achieved. The experts also discussed specific questions during in-depth one-on-one consultation. Outcomes of the discussion were then correlated with published evidence by an independent medical writer. The final consensus includes clinically implementable recommendations to provide guidance in treating Taiwanese mCRC patients. The consensus includes criteria for defining fit and unfit intensive treatment patients, treatment goals, treatment considerations of molecular profiles, treatment consideration, and optimal treatment choices between different patient archetypes, including optimal treatment options based on RAS , BRAF , and microsatellite instability (MSI) status. This consensus paper is the second in the Taiwan Society of Colon and Rectal Surgeons (TSCRS) Consensus series to address unmet gaps in guideline recommendations in lieu of Taiwanese mCRC management. Meticulous discussions with experts, the multidisciplinary nature of the working group, and the final drafting of the consensus by independent medical professionals have contributed to the strong scientific value of this consensus.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2021.764912
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 4
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    Table_1.docx
    Frontiers Media SA ; 2024
    In:  Frontiers in Endocrinology Vol. 15 ( 2024-6-4)
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    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 15 ( 2024-6-4)
    Abstract: To explore the correlation between mitochondrial quantity and the blastocyst development timeline as well as their respective contributions to early pregnancy. Methods A retrospective study was conducted using a dataset comprising 2,633 embryos that underwent preimplantation genetic testing for aneuploidy (PGT-A) between January 2016 and December 2023. The study was divided into three subsets to address distinct aspects: the representativeness of a single trophectoderm (TE) biopsy for mitochondrial quantity (n=43), the correlation between morphokinetic features and mitochondrial quantity (n=307), and the association analysis among mitochondrial quantity, blastocyst timeline factor, and reproductive outcomes (n=2,283). Distribution assessment of mitochondrial quantity across an individual blastocyst involved the identification within multiple biopsies and spent culture media. Timeline evaluation included correlating mitochondrial quantity with time-lapse datasets. Finally, multivariate logistic regression models, incorporating potential effectors alongside mitochondrial quantity, were employed to analyze their respective contributions to early pregnancy endpoints. Results Of distribution assessment, mitochondrial quantity exhibited an even distribution across the entire trophectoderm (Spearman’s ρ=0.82), while no detectable mtDNAs in the corresponding spent culture media. Then the timeline correlation study revealed significant association between mitochondrial quantity and blastocyst features of both the day of expanded blastocyst formation (95% Confidence intervals, CIs: 0.27~4.89, p=0.03) and the timing of expanded blastocyst formation (tEB) (95% CIs: -0.24~-0.01, p=0.04) in the regression model, indicating a strong dependency between mitochondrial quantity and the blastocyst development timeline. For the contribution to early pregnancy, multivariate logistic regression models showed that the day of expanded blastocyst formation contributed to four endpoints persistently: positive for HCG (odd ratio, OR: 0.71, p=0.006), gestational sac (OR: 0.78, p=0.04), fetal heartbeat (OR: 0.71, p=0.004), and progression to 14 weeks (OR: 0.69, p=0.002). Contrastingly, no notable correlation was observed between the mitochondrial quantity and these endpoints. Conclusions Strong interaction was observed between mitochondrial quantity and the blastocyst timeline, particularly the timing of expanded blastocyst formation. It suggests that the primary determinant influencing pregnancy outcomes lies in the time-dependent parameter of blastocyst rather than in the specific mitochondrial quantity.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fendo.2024.1415865
    DOI: 10.3389/fendo.2024.1415865.s001
    DOI: 10.3389/fendo.2024.1415865.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2592084-4
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  • 5
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Cellular Neuroscience Vol. 16 ( 2022-8-9)
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    In: Frontiers in Cellular Neuroscience, Frontiers Media SA, Vol. 16 ( 2022-8-9)
    Abstract: Acupuncture or electroacupuncture (EA) appears to be a potential treatment in acute clinical traumatic brain injury (TBI); however, it remains uncertain whether acupuncture affects post-TBI histone deacetylase (HDAC) expression or impacts other biochemical/neurobiological events. Materials and methods We used behavioral testing, Western blot, and immunohistochemistry analysis to evaluate the cellular and molecular effects of EA at LI4 and LI11 in both weight drop-impact acceleration (WD)- and controlled cortical impact (CCI)-induced TBI models. Results Both WD- and CCI-induced TBI caused behavioral dysfunction, increased cortical levels of HDAC1 and HDAC3 isoforms, activated microglia and astrocytes, and decreased cortical levels of BDNF as well as its downstream mediators phosphorylated-Akt and phosphorylated-GSK-3β. Application of EA reversed motor, sensorimotor, and learning/memory deficits. EA also restored overexpression of HDAC1 and HDAC3, and recovered downregulation of BDNF-associated signaling in the cortex of TBI mice. Conclusion The results strongly suggest that acupuncture has multiple benefits against TBI-associated adverse behavioral and biochemical effects and that the underlying mechanisms are likely mediated by targeting HDAC overexpression and aberrant BDNF-associated Akt/GSK-3 signaling.
    Type of Medium: Online Resource
    ISSN: 1662-5102
    URL: Article
    URL: Article
    DOI: 10.3389/fncel.2022.880267
    DOI: 10.3389/fncel.2022.880267.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2452963-1
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  • 6
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    Table1.DOCX
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-8-5)
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    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-8-5)
    Abstract: The aim of the study was to assess the relationship between prolactin levels and sexual dysfunction in patients with schizophrenia who use olanzapine medication. The potential risk factors of hyperprolactinemia and sexual dysfunction were also investigated. Patients with schizophrenia undergoing olanzapine monotherapy were invited to participate in this cross-sectional study. The Arizona Sexual Experiences Scale (ASEX) and the Positive and Negative Syndrome Scale were used to evaluate subjective sexual dysfunction and psychopathology, respectively. Levels of prolactin and metabolic parameters were also measured. In total, 279 participants with schizophrenia were recruited. The overall incidences of hyperprolactinemia, sexual dysfunction, and metabolic syndrome were 51.6, 53.8, and 43.7%, respectively. Higher ASEX scores, higher insulin levels, female sex, and younger age were associated with hyperprolactinemia. Prolactin level was significantly correlated with ASEX score. Elevated prolactin levels, concomitant antidepressant, increased insulin resistance, longer illness duration, and female sex were associated with sexual dysfunction. Female participants recorded higher levels of sexual dysfunction than their male counterparts did, whereas male participants had comparatively lower prolactin levels and lower rates of spousal partnership. Hyperprolactinemia, metabolic syndrome, and sexual dysfunction are prevalent in patients with schizophrenia treated with olanzapine. Clinicians should maintain awareness of these problems and monitor them regularly with their patients.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2021.718800
    DOI: 10.3389/fphar.2021.718800.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 7
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    Data_Sheet_1.PDF
    Frontiers Media SA ; 2021
    In:  Frontiers in Medicine Vol. 8 ( 2021-12-17)
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    In: Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2021-12-17)
    Abstract: Objective: Sepsis is life threatening and leads to complex inflammation in patients with immunocompromised conditions, such as cancer, and receiving immunosuppressants for autoimmune diseases and organ transplant recipients. Increasing evidence has shown that RNA-Sequencing (RNA-Seq) can be used to define subendotype in patients with sepsis; therefore, we aim to use RNA-Seq to identify transcriptomic features among immunocompromised patients with sepsis. Methods: We enrolled patients who were admitted to medical intensive care units (ICUs) for sepsis at a tertiary referral centre in central Taiwan. Whole blood on day-1 and day-8 was obtained for RNA-Seq. We used Gene Set Enrichment Analysis (GSEA) to identify the enriched pathway of day-8/day-1 differentially expressed genes and MiXCR to determine the diversity of T cell repertoire. Results: A total of 18 immunocompromised subjects with sepsis and 18 sequential organ failure assessment (SOFA) score-matched immunocompetent control subjects were enrolled. The ventilator-day, ICU-stay, and hospital-day were similar between the two groups, whereas the hospital mortality was higher in immunocompromised patients than those in immunocompetent patients (50.0 vs. 5.6%, p & lt; 0.01). We found that the top day-8/day-1 upregulated genes in the immunocompetent group were mainly innate immunity and inflammation relevant genes, namely, PRSS33, HDC, ALOX15, FCER1A , and OLR1 , whereas a blunted day-8/day-1 dynamic transcriptome was found among immunocompromised patients with septic. Functional pathway analyses of day-8/day-1 differentially expressed genes identified the upregulated functional biogenesis and T cell-associated pathways in immunocompetent patients recovered from sepsis, whereas merely downregulated metabolism-associated pathways were found in immunocompromised patients with septic. Moreover, we used MiXCR to identify a higher diversity of T cell receptor (TCR) in immunocompetent patients both on day-1 and on day-8 than those in immunocompromised patients. Conclusions: Using RNA-Seq, we found compromised T cell function, altered metabolic signalling, and decreased T cell diversity among immunocompromised patients with septic, and more mechanistic studies are warranted to elucidate the underlying mechanism.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2021.747263
    DOI: 10.3389/fmed.2021.747263.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2775999-4
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  • 8
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    DataSheet_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-12-8)
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    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-12-8)
    Abstract: Clonality assessment, which can detect neoplastic T cells by identifying the uniquely recombined T-cell receptor (TCR) genes, provides important support in the diagnosis of T-cell lymphoma (TCL). BIOMED-2 is the gold standard clonality assay and has proven to be effective in European TCL patients. However, we failed to prove its sensitivity in Taiwanese TCL patients, especially based on the TCRβ gene. To explore potential impact of genetic background in the BIOMED-2 test, we analyzed TCRβ sequences of 21 healthy individuals and two TCL patients. This analysis suggests that genetic variations in the BIOMED-2 primer sites could not explain the difference in sensitivity. The BIOMED-2 test results of the two TCL patients were positive and negative, respectively. Interestingly, a higher percentage ( & gt;81%) of non-recombined TCRβ sequences was observed in the test-negative patient than those of the test-positive patient and all healthy individuals (13~66%). The result suggests a new TCR target for enhancing TCL diagnosis. To further explore the hypothesis, we proposed a cost-effective digital PCR assay that quantifies the relative abundance of non-recombined TCRβ sequences containing a J2-2P~J2-3 segment. With the digital PCR assay, bone marrow specimens from TCL patients (n=9) showed a positive outcome (i.e., the relative abundance of the J2-2P~J2-3 sequences ≧5%), whereas non-TCL patients (n=6) gave a negative result. As five of nine TCL patients had a negative BIOMED-2 test result, the J2-2P~J2-3 sequences may improve TCL detection. This is the first report showing the capability of characterizing non-recombined TCR sequences as a supplementary strategy for the BIOMED-2 clonality test.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.1014132
    DOI: 10.3389/fonc.2022.1014132.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 9
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    DataSheet_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-8-1)
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    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-8-1)
    Abstract: To investigate the differences between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with autoimmune rheumatic diseases (AIRD), and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) using single-cell RNA sequencing (scRNA-seq). Methods From September 16 to December 10, 2021, we consecutively enrolled 445 participants (389 patients with AIRD and 56 healthy controls), of whom 236 were immunized with AZD1222 and 209 with mRNA-1273. The serum IgG antibodies to the SARS-CoV-2 receptor-binding domain was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients at 4-6 weeks after vaccination for scRNA-seq and further analyzed by CellChat. ScRNA-seq of PBMCs samples from GSE201534 in the Gene Expression Omnibus (GEO) database were also extracted for analysis. Results The anti-SARS-CoV-2 IgG seropositivity rate was 85.34% for AIRD patients and 98.20% for healthy controls. The anti-SARS-CoV-2 IgG level was higher in patients receiving mRNA-1273 than those receiving AZD1222 (β: 35.25, 95% CI: 14.81-55.68, p=0.001). Prednisolone-equivalent dose & gt;5 mg/day and methotrexate use in AIRD patients, and non-anti-tumor necrosis factor-α biologics and Janus kinase inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16 - monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibodies, and enriched pathways related to antigen presentation via MHC class II were found. HLA-DRA and CD4 interaction was enhanced in high anti-SARS-CoV2-IgG group. Conclusions mRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in AIRD patients. Enriched pathways related to antigen presentation via MHC class II in CD16 - monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.920865
    DOI: 10.3389/fimmu.2022.920865.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 10
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    Table_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-9-24)
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    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-9-24)
    Abstract: Lung cancer in never-smokers is a distinct disease associated with a different genomic landscape, pathogenesis, risk factors, and immune checkpoint inhibitor responses compared to those observed in smokers. This study aimed to identify novel single nucleotide polymorphisms (SNPs) of programmed death-1 (encoded by PDCD1 ) and its ligands, programmed death ligand 1 ( CD274 ) and 2 ( PDCD1LG2 ), associated with lung cancer risk in never-smoking women. Materials and Methods During September 2002 and July 2012, we enrolled never-smoking female patients with lung adenocarcinoma (LUAD) (n=1153) and healthy women (n=1022) from six tertiary hospitals in Taiwan. SNP data were obtained and analyzed from the genome-wide association study dataset and through an imputation method. The expression quantitative trait loci (eQTL) analysis was performed in both tumor and non-tumor tissues for the correlation between genetic expression and identified SNPs. Results A total of 12 PDCD1LG2 SNPs related to LUAD risk were identified in never-smoking women, including rs2381282, rs4742103, rs4237162, rs4742104, rs12237624, rs78096119, rs6476988, rs7857315, rs10975178, rs7854413, rs56001683, and rs7858319. Among them, six tagged PDCD1LG2 SNPs rs2381282, rs4742103, rs4237162, rs4742104, rs78096119, and rs56001683 were significantly associated with LUAD risk. Specifically, two PDCD1LG2 SNPs, rs12237624 and rs78096119, were associated with previous pulmonary tuberculosis infection in relation to LUAD susceptibility. Through an eQTL assay, we found that rs2381282 ( p & lt; 0.001), rs12237624 ( p = 0.019), and rs78096119 ( p = 0.019) were associated with the expression levels of programed death ligand 2. Conclusions Novel SNPs of programed death ligand 2 associated with lung adenocarcinoma risk were identified. Among them, two SNPs were associated with pulmonary tuberculosis infection in relation to lung adenocarcinoma susceptibility. These SNPs may help to stratify high-risk populations of never-smokers during lung cancer screening.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.753788
    DOI: 10.3389/fonc.2021.753788.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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