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  • Frontiers Media SA  (6)
  • 1
    Online Resource
    Online Resource
    Population pharmacokinetics of voriconazole and initial dosage optimization in patients with talaromycosis
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-9-26)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-9-26)
    Abstract: The high variability and unpredictability of the plasma concentration of voriconazole (VRC) pose a major challenge for clinical administration. The aim of this study was to develop a population pharmacokinetics (PPK) model of VRC and identify the factors influencing VRC PPK in patients with talaromycosis. Medical records and VRC medication history of patients with talaromycosis who were treated with VRC as initial therapy were collected. A total of 233 blood samples from 69 patients were included in the study. A PPK model was developed using the nonlinear mixed-effects models (NONMEM). Monte Carlo simulation was applied to optimize the initial dosage regimens with a therapeutic range of 1.0–5.5 mg/L as the target plasma trough concentration. A one-compartment model with first-order absorption and elimination adequately described the data. The typical voriconazole clearance was 4.34 L/h, the volume of distribution was 97.4 L, the absorption rate constant was set at 1.1 h -1 , and the bioavailability was 95.1%. Clearance was found to be significantly associated with C-reactive protein (CRP). CYP2C19 polymorphisms had no effect on voriconazole pharmacokinetic parameters. ‏Monte Carlo simulation based on CRP levels showed that a loading dose of 250 mg/12 h and a maintenance dose of 100 mg/12 h are recommended for patients with CRP ≤ 96 mg/L, whereas a loading dose of 200 mg/12 h and a maintenance dose of 75 mg/12 h are recommended for patients with CRP & gt; 96 mg/L. The average probability of target attainment of the optimal dosage regimen in CRP ≤ 96 mg/L and CRP & gt; 96 mg/L groups were 61.3% and 13.6% higher than with empirical medication, and the proportion of C min & gt; 5.5 mg/L decreased by 28.9%. In conclusion, the VRC PPK model for talaromycosis patients shows good robustness and predictive performance, which can provide a reference for the clinical individualization of VRC. Adjusting initial dosage regimens based on CRP may promote the rational use of VRC.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2022.982981
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 2
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    Online Resource
    A Novel Adjustable EndoButton Fixation Assisted by 3D Printing Technology for Tibiofibular Syndesmosis Injury: A Biomechanical Study
    Frontiers Media SA ; 2022
    In:  Frontiers in Bioengineering and Biotechnology Vol. 10 ( 2022-3-10)
    Details
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 10 ( 2022-3-10)
    Abstract: Purpose: The recommendations for surgical fixation of tibiofibular syndesmosis injuries are increasingly challenging for many clinical orthopedists, as international consensus has not been published for the optimal treatment of the injury. Thus, we have created a 3D-printed navigation template for a precise bone tunnel and a novel adjustable EndoButton fixation (NAE) for the ideal treatment. The purpose of this research was to evaluate the accuracy of the 3D-printed navigation template and explore the biomechanical performance of the NAE technique by comparing it with the intact syndesmosis, screw technique, and TightRope (TR) technique. Methods: Twenty-four human cadaveric legs were randomly allocated to four groups: the NAE group ( n = 6), TR group ( n = 6), screw group ( n = 6), and intact group ( n = 6). A personalized navigation template based on computed tomography scans was designed, and 3D printing models were generated for the distal tibiofibular syndesmosis. The NAE, TR, and screw group were performed via 3D-printed navigation template, respectively. All groups were tested under increasing loading forces including axial loading (from 100 N to 700 N) and torsional loading (from 1 N to 5 N), which were performed in different ankle positions. The displacements of the tibiofibular syndesmosis were analyzed using the Bose Electroforce 3510-AT biomechanical testing equipment. Results: Surgical fixations were conducted successfully through a 3D-printed navigation template. Both in axial or torsional loading experiments, no statistically significant difference was observed in the displacements among the NAE, TR, and intact groups in most situations ( p & gt; 0.05), whereas the screw group demonstrated obviously smaller displacements than the abovementioned three groups ( p & lt; 0.05). Conclusion: The 3D printing technology application may become beneficial and favorable for locating and making the bone tunnel. Also, the NAE fixation provides the performance of complete ligaments; it also restores physiologic micromotion and avoids insufficient or excessive reduction when compared to the TR and screw technique. This may offer a new fixation for the treatment of tibiofibular syndesmosis injuries that is desirable for clinical promotion.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    URL: Article
    DOI: 10.3389/fbioe.2022.793866
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2719493-0
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  • 3
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    Online Resource
    Leonurine Promotes the Osteoblast Differentiation of Rat BMSCs by Activation of Autophagy via the PI3K/Akt/mTOR Pathway
    Frontiers Media SA ; 2021
    In:  Frontiers in Bioengineering and Biotechnology Vol. 9 ( 2021-2-23)
    Details
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 9 ( 2021-2-23)
    Abstract: Leonurine, a major bioactive component from Herba leonuri , has been shown to exhibit anti-inflammatory and antioxidant effects. The aim of this study was to investigate the effect of leonurine on bone marrow-derived mesenchymal stem cells (BMSCs) as a therapeutic approach for treating osteoporosis. Materials and Methods Rat bone marrow-derived mesenchymal stem cells (rBMSCs) were isolated from 4-weeks-old Sprague–Dawley rats. The cytocompatibility of leonurine on rBMSCs was tested via CCK-8 assays and flow cytometric analyses. The effects of leonurine on rBMSC osteogenic differentiation were analyzed via ALP staining, Alizarin red staining, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. Additionally, autophagy-related markers were examined via qRT-PCR and Western blot analyses of rBMSCs during osteogenic differentiation with leonurine and with or without 3-methyladenine (3-MA) as an autophagic inhibitor. Finally, the PI3K/Akt/mTOR signaling pathway was evaluated during rBMSC osteogenesis. Results Leonurine at 2–100 μM promoted the proliferation of rBMSCs. ALP and Alizarin red staining results showed that 10 μM leonurine promoted rBMSC osteoblastic differentiation, which was consistent with the qRT-PCR and Western blot results. Compared with those of the control group, the mRNA and protein levels of Atg5, Atg7, and LC3 were upregulated in the rBMSCs upon leonurine treatment. Furthermore, leonurine rescued rBMSC autophagy after inhibition by 3-MA. Additionally, the PI3K/AKT/mTOR pathway was activated in rBMSCs upon leonurine treatment. Conclusion Leonurine promotes the osteoblast differentiation of rBMSCs by activating autophagy, which depends on the PI3K/Akt/mTOR pathway. Our results suggest that leonurine may be a potential treatment for osteoporosis.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    URL: Article
    DOI: 10.3389/fbioe.2021.615191
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2719493-0
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  • 4
    Online Resource
    Online Resource
    Presentation_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Neuroscience Vol. 16 ( 2022-12-15)
    Details
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 16 ( 2022-12-15)
    Abstract: This study aimed to identify the neurophysiologic bases of auditory attention deficits in children with attention-deficit/hyperactivity disorder (ADHD), focusing on the electroencephalography component of auditory spatial selective attention [the N2 anterior contralateral component (N2ac)]. EEG data were collected from 7- to 11-year-old children with ADHD ( n = 54) and age-, sex-, and IQ-matched typically developing (TD) children ( n = 61), while they performed an auditory spatial selective task. For behavior, the children with ADHD showed a shorter reaction time (RT) but a higher RT coefficient of variability (RT CV ) than TD children. For ERPs, the TD group showed a significant “adult-like” N2ac component; however, the N2ac component was absent in children with ADHD. More importantly, the smaller N2ac component could predict longer RT in both groups, as well as higher severity of inattentive symptoms in children with ADHD. Our results indicated that 7- to 11-year-old TD children have developed an “adult-like” ability to balance auditory target selection and distractor suppression; the absence of N2ac in children with ADHD provided novel evidence supporting their dysfunctional auditory spatial selective attention.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    URL: Article
    URL: Article
    DOI: 10.3389/fnins.2022.1051585
    DOI: 10.3389/fnins.2022.1051585.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2411902-7
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  • 5
    Online Resource
    Online Resource
    Table1.DOCX
    Frontiers Media SA ; 2022
    In:  Frontiers in Bioengineering and Biotechnology Vol. 9 ( 2022-1-11)
    Details
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 9 ( 2022-1-11)
    Abstract: Object: The aims of the study were to explore the protective effects of S-propargyl-cysteine (SPRC) on periodontitis and to determine the underlying mechanisms. Methods: A rat periodontitis model was constructed by injecting LPS and SPRC (0, 25, and 50 mg/kg/d) was administered intraperitoneally. H2S and CSE level were detected. The alveolar bone level was evaluated by micro-CT, HE staining and methylene blue staining analysis. Inflammation-related factors, Treg and Th17 cells were detected by immunohistochemistry, RT-PCR, immunofluorescence, Western blot and flow cytometry. Phosphorylation levels of ERK1/2 and CREB were analysed. Results: The administration of SPRC significantly increased the expression of CSE in the gingival tissue and the concentration of endogenous H2S in the peripheral blood. Simultaneously, SPRC significantly inhibited the resorption of alveolar bone based on the H & amp;E staining, micro-CT and methylene blue staining analysis. Compared with the periodontitis group, the levels of IL-17A, IL-10 were downregulated and IL-6,TGF-β1 were upregulated in the SPRC groups. In the SPRC group, the percentage of TH17 cells and the expression of ROR-γt were downregulated, while the percentage of Tregs and the expression of Foxp3 were upregulated accompanied with inhibition of phosphorylation ERK1/2 and CREB. Conclusion: SPRC can prevent the progression of periodontitis by regulating the Th17/Treg balance by inhibition of the ERK/CREB signalling pathway.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fbioe.2021.737334
    DOI: 10.3389/fbioe.2021.737334.s001
    DOI: 10.3389/fbioe.2021.737334.s002
    DOI: 10.3389/fbioe.2021.737334.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2719493-0
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  • 6
    Online Resource
    Online Resource
    Image_4.tif
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-3-21)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-3-21)
    Abstract: Urothelial carcinoma of the bladder (UCB) is a major type of bladder cancer with a distinct tumor microenvironment (TME). Although neutrophils are the main component of myeloid cells in the TME, the clinical significance and function of the neutrophils remain unclear in UCB. Here, we observed CD66b+ neutrophils were predominantly enriched in the stroma of UCB tissues and their levels emerged as an independent prognostic factor for overall survival ( P = 0.006, n = 237), and were positively associated with age ( P = 0.033), tumor stage ( P & lt; 0.0001), nodal metastasis ( P = 0.045), and histological grade ( P & lt; 0.0001). Furthermore, we found that CD66b + neutrophils were frequently co-localized with CD4 + T cells (R=0.35, P = 0.0067), CD8 + T cells (R=0.52, P & lt;0.0001) and Cleaved Caspase-3 + apoptosis cells (R=0.44, P = 0.0007) in the stroma of UCB tissue. In addition, better effects of T cells on patients’ survival were markedly reduced by neutrophils and T cells co-infiltration. Moreover, we confirmed bladder tumor cell supernatant treated neutrophils suppressed T cell proliferation and activation, and promoted T cell apoptosis through GM-CSF induced PD-L1 in vitro . The expression of PD-L1 by neutrophils was also detected in fresh UCB tissues by using flow cytometric analysis. These data suggested that stromal CD66b+ neutrophils may potentially represent a reliable marker of poor prognosis for UCB patients, and neutrophils might play an immunosuppressive role on T cell immunity partially via the expression of PD-L1.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.827457
    DOI: 10.3389/fimmu.2022.827457.s001
    DOI: 10.3389/fimmu.2022.827457.s002
    DOI: 10.3389/fimmu.2022.827457.s003
    DOI: 10.3389/fimmu.2022.827457.s004
    DOI: 10.3389/fimmu.2022.827457.s005
    DOI: 10.3389/fimmu.2022.827457.s006
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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