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  • Frontiers Media SA  (189)
  • 1
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    DataSheet_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-11-16)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-11-16)
    Abstract: Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or & lt;5 patients per year, p = 0.12) or age (≥60 or & lt;60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count ( & gt;10 × 10 9 /L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.762653
    DOI: 10.3389/fonc.2021.762653.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 2
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    Table_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-5-10)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-5-10)
    Abstract: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a major strategy to cure patients with acute lymphoblastic leukemia (ALL). The aim of this study was to evaluate whether isolated flow cytometry (FCM)-positive central nervous system (CNS) involvement before allo-HSCT is clinically significant. Methods The effects of isolated FCM-positive CNS involvement prior to transplantation on the outcomes of 1406 ALL patients with complete remission (CR) were retrospectively investigated. Results Patients were classified into isolated FCM-positive CNS involvement (n=31), cytology-positive CNS involvement (n = 43), and negative CNS involvement (n = 1332) groups. Among the three groups, the 5-year cumulative incidence of relapse (CIR) values were 42.3%, 48.8%, and 23.4%, respectively ( P & lt;0.001). The 5-year leukemia-free survival (LFS) values were 44.7%, 34.9%, and 60.8%, respectively ( P & lt;0.001). Compared with the negative CNS group (n=1332), the 5-year CIR of the pre-HSCT CNS involvement group (n=74) was higher (46.3% vs . 23.4%, P & lt;0.001], and the 5-year LFS was inferior (39.1% vs . 60.8%, P & lt;0.001). Multivariate analysis indicated that four variables, T-cell ALL, in second complete remission or beyond (CR2+) at HSCT, pre-HSCT measurable residual disease positivity, and pre-HSCT CNS involvement, were independently associated with a higher CIR and inferior LFS. A new scoring system was developed using the following four variables: low-risk, intermediate-risk, high-risk, and extremely high-risk groups. The 5-year CIR values were 16.9%, 27.8%, 50.9%, and 66.7%, respectively ( P & lt;0.001), while the 5-year LFS values were 67.6%, 56.9%, 31.0%, and 13.3%, respectively ( P & lt;0.001). Conclusion Our results suggest that ALL patients with isolated FCM-positive CNS involvement are at a higher risk of recurrence after transplantation. Patients with pre-HSCT CNS involvement had higher CIR and inferior survival outcomes.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2023.1166990
    DOI: 10.3389/fonc.2023.1166990.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 3
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    Table_1.xlsx
    Frontiers Media SA ; 2022
    In:  Frontiers in Microbiology Vol. 13 ( 2022-4-8)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 13 ( 2022-4-8)
    Abstract: The roles of gut microbiota and metabolomics in women with gestational diabetes mellitus (GDM) are not well understood. This study investigated the gut metabolomic profiling of GDM rats and GDM rats treated with probiotic supplements. Associations between gut metabolites and microbiota were also studied in GDM rats. Liquid chromatography–mass spectrometry was used to detect gut metabolites in GDM rats and GDM rats treated with probiotic supplements of 0.5 g (low-dose group) or 1 g (high-dose group) for 15 days. Each gram of probiotic supplement contained 5 × 10 7 colony-forming units (CFU) of Lactobacillus rhamnosus LGG and 1 × 10 8 CFU of Bifidobacterium animalis subspecies lactis Bb12. The association between gut metabolites and microbiota in GDM rats was investigated using Spearman’s correlation. Finally, 10 rats in the normal pregnant group, eight rats in the GDM model group, eight GDM rats in the low-dose probiotics group, and nine GDM rats in the high-dose probiotics group were further studied. Serum parameters and pancreatic and colon histology were significantly changed in GDM rats, and these were restored using probiotic supplements. In total, 999 gut metabolites were detected in the feces, and GDM rats were distinguished from normal rats. The levels of 44 metabolites were increased in GDM rats, and they were alleviated using probiotic supplements. Changes in metabolites in GDM rats were associated with amino acids and bile acids metabolism signaling pathways. Furthermore, changes in metabolites after probiotic supplementation were associated with porphyrin and chlorophyll metabolism pathways. We found that the Allobaculum genus displayed strong positive correlations, whereas the Bryobacter and Gemmatimonas genera displayed strong negative correlations with metabolisms of amino acids and bile acids in GDM rats. The Lactobacillus and Bifidobacterium genera were positively correlated with gut metabolites. Overall, our results showed that metabolism signaling pathways of amino acids and bile acids are associated with the development of GDM. Probiotic supplements alleviate the pathology of GDM through the metabolism pathways of amino acids, bile acids, porphyrin, and chlorophyll.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmicb.2022.779314
    DOI: 10.3389/fmicb.2022.779314.s001
    DOI: 10.3389/fmicb.2022.779314.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587354-4
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  • 4
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    Table_1.PDF
    Frontiers Media SA ; 2018
    In:  Frontiers in Neurology Vol. 8 ( 2018-1-19)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 8 ( 2018-1-19)
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fneur.2017.00755
    DOI: 10.3389/fneur.2017.00755.s001
    DOI: 10.3389/fneur.2017.00755.s002
    DOI: 10.3389/fneur.2017.00755.s003
    DOI: 10.3389/fneur.2017.00755.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2564214-5
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  • 5
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    Calcium Signaling Regulated by Cellular Membrane Systems and Calcium Homeostasis Perturbed in Alzheimer’s Disease
    Frontiers Media SA ; 2022
    In:  Frontiers in Cell and Developmental Biology Vol. 10 ( 2022-2-25)
    Details
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 10 ( 2022-2-25)
    Abstract: Although anything that changes spatiotemporally could be a signal, cells, particularly neurons, precisely manipulate calcium ion (Ca 2+ ) to transmit information. Ca 2+ homeostasis is indispensable for neuronal functions and survival. The cytosolic Ca 2+ concentration ([Ca 2+ ] CYT ) is regulated by channels, pumps, and exchangers on cellular membrane systems. Under physiological conditions, both endoplasmic reticulum (ER) and mitochondria function as intracellular Ca 2+ buffers. Furthermore, efficient and effective Ca 2+ flux is observed at the ER-mitochondria membrane contact site (ERMCS), an intracellular membrane juxtaposition, where Ca 2+ is released from the ER followed by mitochondrial Ca 2+ uptake in sequence. Hence, the ER intraluminal Ca 2+ concentration ([Ca 2+ ] ER ), the mitochondrial matrix Ca 2+ concentration ([Ca 2+ ] MT ), and the [Ca 2+ ] CYT are related to each other. Ca 2+ signaling dysregulation and Ca 2+ dyshomeostasis are associated with Alzheimer’s disease (AD), an irreversible neurodegenerative disease. The present review summarizes the cellular and molecular mechanism underlying Ca 2+ signaling regulation and Ca 2+ homeostasis maintenance at ER and mitochondria levels, focusing on AD. Integrating the amyloid hypothesis and the calcium hypothesis of AD may further our understanding of pathogenesis in neurodegeneration, provide therapeutic targets for chronic neurodegenerative disease in the central nervous system.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    URL: Article
    DOI: 10.3389/fcell.2022.834962
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2737824-X
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  • 6
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    Table4.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-7-6)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-7-6)
    Abstract: Background: There is a substantial lack of tacrolimus pharmacokinetic information in pediatric hematopoietic stem cell transplant (HSCT) patients. This study aimed to develop population pharmacokinetics (PopPK) of tacrolimus in pediatric HSCT patients and to devise model-guided dosage regimens. Methods: A retrospective analysis was performed on 86 pediatric HSCT patients who received tacrolimus intravenously or orally. A total of 578 tacrolimus trough concentrations (C 0 ) were available for pharmacokinetic analysis using a non-linear mixed-effects modeling method. Demographic and clinical data were included and assessed as covariates via the stepwise method. Bayesian estimators were used to devise pediatric dosage regimens that targeted C 0 of 5–15 ng mL −1 . Results: A one-compartment model with first-order absorption adequately described the tacrolimus pharmacokinetics. Clearance (CL), volume of distribution (V), and typical bioavailability (F) in this study were estimated to be 2.42 L h −1 (10.84%), 79.6 L (16.51%), and 19% (13.01%), respectively. Body weight, hematocrit, post-transplantation days, and caspofungin and azoles concomitant therapy were considered significant covariates for tacrolimus CL. Hematocrit had a significant impact on the V of tacrolimus. In the subgroup cohort of children ( n = 24) with CYP3A5 genotype, the clearance was 1.38-fold higher in CYP3A5 expressers than in non-expressers. Simulation indicated that the initial dosage optimation of tacrolimus for intravenous and oral administration was recommended as 0.025 and 0.1 mg kg −1  d −1 (q12h), respectively. Conclusion: A PopPK model for tacrolimus in pediatric HSCT patients was developed, showing good predictive performance. Model-devised dosage regimens with trough tacrolimus concentrations provide a practical strategy for achieving the therapeutic range.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.891648
    DOI: 10.3389/fphar.2022.891648.s001
    DOI: 10.3389/fphar.2022.891648.s002
    DOI: 10.3389/fphar.2022.891648.s003
    DOI: 10.3389/fphar.2022.891648.s004
    DOI: 10.3389/fphar.2022.891648.s005
    DOI: 10.3389/fphar.2022.891648.s006
    DOI: 10.3389/fphar.2022.891648.s007
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
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  • 7
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    Data_Sheet_4.PDF
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-4-5)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-4-5)
    Abstract: Patients with pulmonary arterial hypertension (PAH) have reduced exercise capacity and poor quality of life. Exercise-based rehabilitation in PAH results in clinically relevant improvements in exercise capacity and hemodynamics. To clarify the mechanism, we will evaluate the effect of aerobic exercise training rehabilitation on right ventricular (RV) remodeling and function as determined measured by cardiac magnetic resonance imaging (CMR). Methods We will conduct a 26-week multicenter randomized controlled trial. Patients on stable and unchanged PAH-targeted medication are randomly assigned (1:1) to the control and training groups. The primary endpoint is the RV stroke volume (RVSV) change from baseline to Week 26, determined by CMR. Comprehensive RV function is also performed using CMR. Other characteristics of the RV and left ventricle, World Health Organization functional class, 6-min walk distance, and N-terminal pro-B-type natriuretic peptide are included in secondary endpoints. We also investigate the proteomic, metabolomic, and transcriptomic changes after exercise training as exploratory endpoints. Ethics and Dissemination The study and protocol were approved by the Ethics Committee of Shanghai Pulmonary Hospital (Approved No. of ethics committee: L20-17). The results will be disseminated at medical conferences and in journal publications. All participants will sign written informed consent. Trial Registration Number ChiCTR2000031650.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2022.835272
    DOI: 10.3389/fmed.2022.835272.s001
    DOI: 10.3389/fmed.2022.835272.s002
    DOI: 10.3389/fmed.2022.835272.s003
    DOI: 10.3389/fmed.2022.835272.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 8
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    NaHS or Lovastatin Attenuates Cyclosporine A–Induced Hypertension in Rats by Inhibiting Epithelial Sodium Channels
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-5-26)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-5-26)
    Abstract: The use of cyclosporine A (CsA) in transplant recipients is limited due to its side effects of causing severe hypertension. We have previously shown that CsA increases the activity of the epithelial sodium channel (ENaC) in cultured distal nephron cells. However, it remains unknown whether ENaC mediates CsA-induced hypertension and how we could prevent hypertension. Our data show that the open probability of ENaC in principal cells of split-open cortical collecting ducts was significantly increased after treatment of rats with CsA; the increase was attenuated by lovastatin. Moreover, CsA also elevated the levels of intracellular cholesterol (Cho), intracellular reactive oxygen species (ROS) via activation of NADPH oxidase p47 phox , serum- and glucocorticoid-induced kinase isoform 1 (Sgk1), and phosphorylated neural precursor cell–expressed developmentally downregulated protein 4–2 ( p -Nedd4-2) in the kidney cortex. Lovastatin also abolished CsA-induced elevation of α-, ß -, and γ-ENaC expressions. CsA elevated systolic blood pressure in rats; the elevation was completely reversed by lovastatin (an inhibitor of cholesterol synthesis), NaHS (a donor of H 2 S which ameliorated CsA-induced elevation of reactive oxygen species), or amiloride (a potent ENaC blocker). These results suggest that CsA elevates blood pressure by increasing ENaC activity via a signaling cascade associated with elevation of intracellular ROS, activation of Sgk1, and inactivation of Nedd4-2 in an intracellular cholesterol-dependent manner. Our data also show that NaHS ameliorates CsA-induced hypertension by inhibition of oxidative stress.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2021.665111
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
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  • 9
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    DataSheet_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-8-17)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-8-17)
    Abstract: Approximately 30% of Chinese individuals with cytogenetically normal acute myeloid leukemia (CN-AML) have biallelic CEBPA (bi CEBPA ) mutations. The prognosis and optimal therapy for these patients are controversial in clinical practice. Methods In this study, we performed targeted region sequencing of 236 genes in 158 individuals with this genotype and constructed a nomogram model based on leukemia-free survival (LFS). Patients were randomly assigned to a training cohort ( N =111) and a validation cohort ( N =47) at a ratio of 7:3. Risk stratification was performed by the prognostic factors to investigate the risk-adapted post-remission therapy by Kaplan–Meier method. Results At least 1 mutated gene other than CEBPA was identified in patients and mutation number was associated with LFS (61.6% vs. 39.0%, P =0.033), survival (85.6% vs. 62.9%, P  =0.030) and cumulative incidence of relapse (CIR) (38.4% vs. 59.5%, P =0.0496). White blood cell count, mutations in CFS3R , KMT2A and DNA methylation related genes were weighted to construct a nomogram model and differentiate two risk subgroups. Regarding LFS, low-risk patients were superior to the high-risk (89.3% vs. 33.8%, P & lt; 0.001 in training cohort; 87.5% vs. 18.2%, P =0.009 in validation cohort). Compared with chemotherapy, allogenic hematopoietic stem cell transplantation (allo-HSCT) improved 5-year LFS (89.6% vs. 32.6%, P & lt; 0.001), survival (96.9% vs. 63.6%, P =0.001) and CIR (7.2% vs. 65.8%, P  & lt; 0.001) in high-risk patients but not low-risk patients (LFS, 77.4% vs. 88.9%, P =0.424; survival, 83.9% vs. 95.5%, P =0.173; CIR, 11.7% vs. 11.1%, P =0.901). Conclusions Our study indicated that bi CEBPA mutant-positive CN-AML patients could be further classified into two risk subgroups by four factors and allo-HSCT should be recommended for high-risk patients as post-remission therapy. These data will help physicians refine treatment decision-making in bi CEBPA mutant-positive CN-AML patients.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.706935
    DOI: 10.3389/fonc.2021.706935.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 10
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    Table4.XLSX
    Frontiers Media SA ; 2023
    In:  Frontiers in Pharmacology Vol. 14 ( 2023-3-20)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 14 ( 2023-3-20)
    Abstract: The vasopressin/oxytocin signaling system is present in both protostomes and deuterostomes and plays various physiological roles. Although there were reports for both vasopressin-like peptides and receptors in mollusc Lymnaea and Octopus, no precursor or receptors have been described in mollusc Aplysia . Here, through bioinformatics, molecular and cellular biology, we identified both the precursor and two receptors for Aplysia vasopressin-like peptide, which we named Aplysia vasotocin (apVT). The precursor provides evidence for the exact sequence of apVT, which is identical to conopressin G from cone snail venom, and contains 9 amino acids, with two cysteines at position 1 and 6, similar to nearly all vasopressin-like peptides. Through inositol monophosphate (IP1) accumulation assay, we demonstrated that two of the three putative receptors we cloned from Aplysia cDNA are true receptors for apVT. We named the two receptors as apVTR1 and apVTR2. We then determined the roles of post-translational modifications (PTMs) of apVT, i.e., the disulfide bond between two cysteines and the C-terminal amidation on receptor activity. Both the disulfide bond and amidation were critical for the activation of the two receptors. Cross-activity with conopressin S, annetocin from an annelid, and vertebrate oxytocin showed that although all three ligands can activate both receptors, the potency of these peptides differed depending on their residue variations from apVT. We, therefore, tested the roles of each residue through alanine substitution and found that each substitution could reduce the potency of the peptide analog, and substitution of the residues within the disulfide bond tended to have a larger impact on receptor activity than the substitution of those outside the bond. Moreover, the two receptors had different sensitivities to the PTMs and single residue substitutions. Thus, we have characterized the Aplysia vasotocin signaling system and showed how the PTMs and individual residues in the ligand contributed to receptor activity.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
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    URL: Article
    DOI: 10.3389/fphar.2023.1132066
    DOI: 10.3389/fphar.2023.1132066.s001
    DOI: 10.3389/fphar.2023.1132066.s002
    DOI: 10.3389/fphar.2023.1132066.s003
    DOI: 10.3389/fphar.2023.1132066.s004
    DOI: 10.3389/fphar.2023.1132066.s005
    DOI: 10.3389/fphar.2023.1132066.s006
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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