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  • Frontiers Media SA  (1,367)
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  • 1
    Online Resource
    Online Resource
    DataSheet1.PDF
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-6-16)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-6-16)
    Abstract: Background: Presently, colistin is commercially available in two different forms, namely, colistin sulfate and its sulphomethylated derivative, colistimethate sodium (CMS). However, in the currently reported studies, most of the clinical studies on colistin for parenteral use are referred to as CMS. Data on the pharmacokinetics (PK), clinical efficacy, and side effects of colistin sulfate in clinical use have not been reported. Methods: This retrospective study was performed on carbapenem-resistant organism (CRO)-infected patients treated with colistin sulfate for more than 72 h. The population pharmacokinetic model was developed using the NONMEM program. The clinical outcomes including clinical treatment efficacy, microbiological eradication, and nephrotoxicity were assessed. Monte Carlo simulation was utilized to calculate the probability of target attainment (PTA) in patients with normal or decreased renal function. Results: A total of 42 patients were enrolled, of which 25 (59.52%) patients were considered clinical treatment success and 29 (69.06%) patients had successful bacteria elimination at the end of treatment. Remarkably, no patient developed colistin sulfate-related nephrotoxicity. A total of 112 colistin concentrations with a range of 0.28–6.20 mg/L were included for PK modeling. The PK characteristic of colistin was well illustrated by a one-compartment model with linear elimination, and creatinine clearance (CrCL) was identified as a covariate on the clearance of colistin sulfate that significantly explained inter-individual variability. Monte Carlo simulations showed that the recommended dose regimen of colistin sulfate, according to the label sheet, of a daily dose of 1–1.5 million IU/day, given in 2–3 doses, could attain PTA & gt; 90% for MICs ≤ 0.5 μg/mL, and that a daily dose of 1 million IU/day could pose a risk of subtherapeutic exposure for MIC ≥1 μg/ml in renal healthy patients. Conclusion: Renal function significantly affects the clearance of colistin sulfate. A dose of 750,000 U every 12 h was recommended for pathogens with MIC ≤1 μg/ml. The dosage recommended by the label inserts had a risk of subtherapeutic exposure for pathogens with MIC ≥2 μg/ml. Despite higher exposure to colistin in patients with acute renal insufficiency, dose reduction was not recommended.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.915958
    DOI: 10.3389/fphar.2022.915958.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
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  • 2
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    Combination of multi-modal MRI radiomics and liquid biopsy technique for preoperatively non-invasive diagnosis of glioma based on deep learning: protocol for a double-center, ambispective, diagnostical observational study
    Frontiers Media SA ; 2023
    In:  Frontiers in Molecular Neuroscience Vol. 16 ( 2023-5-2)
    Details
    In: Frontiers in Molecular Neuroscience, Frontiers Media SA, Vol. 16 ( 2023-5-2)
    Abstract: 2021 World Health Organization (WHO) Central Nervous System (CNS) tumor classification increasingly emphasizes the important role of molecular markers in glioma diagnoses. Preoperatively non-invasive “integrated diagnosis” will bring great benefits to the treatment and prognosis of these patients with special tumor locations that cannot receive craniotomy or needle biopsy. Magnetic resonance imaging (MRI) radiomics and liquid biopsy (LB) have great potential for non-invasive diagnosis of molecular markers and grading since they are both easy to perform. This study aims to build a novel multi-task deep learning (DL) radiomic model to achieve preoperative non-invasive “integrated diagnosis” of glioma based on the 2021 WHO-CNS classification and explore whether the DL model with LB parameters can improve the performance of glioma diagnosis. Methods This is a double-center, ambispective, diagnostical observational study. One public database named the 2019 Brain Tumor Segmentation challenge dataset (BraTS) and two original datasets, including the Second Affiliated Hospital of Nanchang University, and Renmin Hospital of Wuhan University, will be used to develop the multi-task DL radiomic model. As one of the LB techniques, circulating tumor cell (CTC) parameters will be additionally applied in the DL radiomic model for assisting the “integrated diagnosis” of glioma. The segmentation model will be evaluated with the Dice index, and the performance of the DL model for WHO grading and all molecular subtype will be evaluated with the indicators of accuracy, precision, and recall. Discussion Simply relying on radiomics features to find the correlation with the molecular subtypes of gliomas can no longer meet the need for “precisely integrated prediction.” CTC features are a promising biomarker that may provide new directions in the exploration of “precision integrated prediction” based on the radiomics, and this is the first original study that combination of radiomics and LB technology for glioma diagnosis. We firmly believe that this innovative work will surely lay a good foundation for the “precisely integrated prediction” of glioma and point out further directions for future research. Clinical trail registration This study was registered on ClinicalTrails.gov on 09/10/2022 with Identifier NCT05536024.
    Type of Medium: Online Resource
    ISSN: 1662-5099
    URL: Article
    DOI: 10.3389/fnmol.2023.1183032
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2452967-9
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  • 3
    Online Resource
    Online Resource
    DataSheet1.ZIP
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-4-11)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-4-11)
    Abstract: Background: Linezolid is associated with myelosuppression, which may cause failure in optimally treating bacterial infections. The study aimed to define the pharmacokinetic/toxicodynamic (PK/TD) threshold for critically ill patients and to identify a dosing strategy for critically ill patients with renal insufficiency. Methods: The population pharmacokinetic (PK) model was developed using the NONMEM program. Logistic regression modeling was conducted to determine the toxicodynamic (TD) threshold of linezolid-induced myelosuppression. The dosing regimen was optimized based on the Monte Carlo simulation of the final model. Results: PK analysis included 127 linezolid concentrations from 83 critically ill patients at a range of 0.25–21.61 mg/L. Creatinine clearance (CrCL) was identified as the only covariate of linezolid clearance that significantly explained interindividual variability. Thirty-four (40.97%) of the 83 patients developed linezolid-associated myelosuppression. Logistic regression analysis showed that the trough concentration (C min ) was a significant predictor of myelosuppression in critically patients, and the threshold for C min in predicting myelosuppression with 50% probability was 7.8 mg/L. The Kaplan–Meier plot revealed that the overall median time from the initiation of therapy to the development of myelosuppression was 12 days. Monte Carlo simulation indicated an empirical dose reduction to 600 mg every 24 h was optimal to balance the safety and efficacy in critically ill patients with CrCL of 30–60 ml/min, 450 mg every 24 h was the alternative for patients with CrCL & lt;30 ml/min, and 600 mg every 12 h was recommended for patients with CrCL ≥60 ml/min. Conclusion: Renal function plays a significant role in linezolid PKs for critically ill patients. A dose of 600 mg every 24 h was recommended for patients with CrCL & lt;60 ml/min to minimize linezolid-induced myelosuppression.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.844567
    DOI: 10.3389/fphar.2022.844567.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
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  • 4
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    The Role of Interleukin-6 Family Members in Cardiovascular Diseases
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-3-23)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-3-23)
    Abstract: Cardiovascular disease is one of the main causes of human mortality. Cytokines play crucial roles in the development of cardiovascular disease. Interleukin (IL)-6 family members are a series of cytokines, including IL-6, IL-11, IL-30, IL-31, OSM, LIF, CNTF, CT-1, CT-2, and CLC, that regulate multiple biological effects. Experimental and clinical evidence shows that IL-6 family members are closely related to cardiovascular diseases such as atherosclerosis, hypertension, aortic dissection, cardiac fibrosis, and cardiomyopathy. This review mainly discusses the role of IL-6 family members in cardiovascular disease for the sake of identifying possible intervention targets for cardiovascular disease prevention and treatment.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    DOI: 10.3389/fcvm.2022.818890
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 5
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    Online Resource
    Molecular Screening for Nigericin Treatment in Pancreatic Cancer by High-Throughput RNA Sequencing
    Frontiers Media SA ; 2020
    In:  Frontiers in Oncology Vol. 10 ( 2020-7-31)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 10 ( 2020-7-31)
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2020.01282
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2649216-7
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  • 6
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    The Role of CXC Chemokines in Cardiovascular Diseases
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 12 ( 2022-5-20)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2022-5-20)
    Abstract: Cardiovascular disease (CVD) is a class of diseases with high disability and mortality rates. In the elderly population, the incidence of cardiovascular disease is increasing annually. Between 1990 and 2016, the age-standardised prevalence of CVD in China significantly increased by 14.7%, and the number of cardiovascular disease deaths increased from 2.51 million to 3.97 million. Much research has indicated that cardiovascular disease is closely related to inflammation, immunity, injury and repair. Chemokines, which induce directed chemotaxis of reactive cells, are divided into four subfamilies: CXC, CC, CX3C, and XC. As cytokines, CXC chemokines are similarly involved in inflammation, immunity, injury, and repair and play a role in many cardiovascular diseases, such as atherosclerosis, myocardial infarction, cardiac ischaemia-reperfusion injury, hypertension, aortic aneurysm, cardiac fibrosis, postcardiac rejection, and atrial fibrillation. Here, we explored the relationship between the chemokine CXC subset and cardiovascular disease and its mechanism of action with the goal of further understanding the onset of cardiovascular disease.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2021.765768
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
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  • 7
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    Table_2.DOCX
    Frontiers Media SA ; 2022
    In:  Frontiers in Plant Science Vol. 13 ( 2022-4-25)
    Details
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 13 ( 2022-4-25)
    Abstract: Grain size, grain number per panicle, and grain weight are key agronomic traits that determine grain yield in rice. However, the molecular mechanisms coordinately controlling these traits remain largely unknown. In this study, we identified a major QTL, SMG3 , that is responsible for grain size, grain number per panicle, and grain weight in rice, which encodes a MYB-like protein. The SMG3 allele from M494 causes an increase in the number of grains per panicle but produces smaller grain size and thousand grain weight. The SMG3 is constitutively expressed in various organs in rice, and the SMG3 protein is located in the nucleus. Microscopy analysis shows that SMG3 mainly produces long grains by increasing in both cell length and cell number in the length direction, which thus enhances grain weight by promoting cell expansion and cell proliferation. Overexpression of SMG3 in rice produces a phenotype with more grains but reduces grain length and weight. Our results reveal that SMG3 plays an important role in the coordinated regulation of grain size, grain number per panicle, and grain weight, providing a new insight into synergistical modification on the grain appearance quality, grain number per panicle, and grain weight in rice.
    Type of Medium: Online Resource
    ISSN: 1664-462X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fpls.2022.880919
    DOI: 10.3389/fpls.2022.880919.s001
    DOI: 10.3389/fpls.2022.880919.s002
    DOI: 10.3389/fpls.2022.880919.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 8
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    Data_Sheet_1.PDF
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 8 ( 2022-1-24)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 8 ( 2022-1-24)
    Abstract: Spontaneous intramuscular hemorrhage (SIH) is a rare but life-threatening complication associated with dermatomyositis (DM). This study reported a case series of SIH associated with DM. In addition, the characteristics and prognostic effects for this complication were analyzed based on literature review. Methods We reported seven cases of anti-melanoma differentiation-associated gene five positive dermatomyositis (MDA5 + DM) complicated by SIH in our single-center cohort, and a comprehensive literature review was performed. Clinical characteristics, treatment, and outcome data of all eligible reported cases were summarized. Potential prognostic effects were identified by comparisons between the deceased and survivors. Results Among cumulatively reported patients with DM patients and SIH, the overall mortality was 60.9% (14/23) (including our cases). Fourteen out of nineteen (73.7%) hemorrhagic events occurred within 6 months of disease onset. Anti-MDA5 antibody predominated in those myositis-specific antibodies available cases (8/10), although patients with positive anti-NXP2 and anti-Mi2 have also been documented. Iliopsoas (52.2%, 12/23) was the most frequently involved bleeding location. Bleeding in deep muscles was identified to be associated with poorer prognosis. The mortality of patients with DM and deep muscular hematoma (non-palpable) (80%, 12/15) was significantly higher than that of patients with only superficial muscular hematoma (palpable) (25%, 2/8) ( p =0.023). Conclusion Spontaneous hematoma in non-palpable deep muscles probably leads to excess mortality in dermatomyositis, particularly for those with anti-MDA5 antibody, which often occurs within 6 months of disease onset. Clinicians should be vigilant to this rare but potentially fatal complication and carefully balance the risks and benefits of prophylactic anti-thrombotic treatment.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    URL: Article
    DOI: 10.3389/fmed.2021.802753
    DOI: 10.3389/fmed.2021.802753.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 9
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    DataSheet1.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-7-2)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-7-2)
    Abstract: Cardiac dysfunction is a well-recognized complication of sepsis and is associated with the outcome and prognosis of septic patients. Evidence suggests that Il12a participates in the regulation of various cardiovascular diseases, including heart failure, hypertension and acute myocardial infarction. However, the effects of Il12a in sepsis-induced cardiac dysfunction remain unknown. In our study, lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) model were used to mimic sepsis, and cardiac Il12a expression was assessed. In addition, Il12a knockout mice were used to detect the role of Il12a in sepsis-related cardiac dysfunction. We observed for the first time that Il12a expression is upregulated in mice after LPS treatment and macrophages were the main sources of Il12a. In addition, our findings demonstrated that Il12a deletion aggravates LPS-induced cardiac dysfunction and injury, as evidenced by the increased serum and cardiac levels of lactate dehydrogenase (LDH) and cardiac creatine kinase-myocardial band (CK-MB). Moreover, Il12a deletion enhances LPS-induced macrophage accumulation and drives macrophages toward the M1 phenotype in LPS-treated mice. Il12a deletion also downregulated the activity of AMP-activated protein kinase (AMPK) but increased the phosphorylation levels of p65 (p-p65) and NF-κB inhibitor alpha (p-IκBα). In addition, Il12a deletion aggravates CLP-induced cardiac dysfunction and injury. Treatment with the AMPK activator AICAR abolishes the deterioration effect of Il12a deletion on LPS-induced cardiac dysfunction. In conclusion, Il12a deletion aggravated LPS-induced cardiac dysfunction and injury by exacerbating the imbalance of M1 and M2 macrophages. Our data provide evidence that Il12a may represent an attractive target for sepsis-induced cardiac dysfunction.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2021.632912
    DOI: 10.3389/fphar.2021.632912.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
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  • 10
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    Data_Sheet_1.DOCX
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-5-12)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-5-12)
    Abstract: Obesity is often accompanied by hypertension. Although a large number of studies have confirmed that NLRP3 inhibitors can improve cardiac remodeling in mice with a normal diet, it is still unclear whether NLRP3 inhibitors can improve heart failure (HF) induced by pressure overload in obese mice. The purpose of this study was to explore the role of MCC950, a selective NLRP3 inhibitor, on HF in obese mice and its metabolic mechanism. Obese mice induced with a 10-week high-fat diet (HFD) were used in this study. After 4 weeks of HFD, transverse aortic constriction (TAC) surgery was performed to induce a HF model. MCC950 (10 mg/kg, once/day) was injected intraperitoneally from 2 weeks after TAC and continued for 4 weeks. After echocardiography examination, we harvested left ventricle tissues and performed molecular experiments. The results suggest that in obese mice, MCC950 can significantly improve cardiac hypertrophy and fibrosis caused by pressure overload. MCC950 ameliorated cardiac inflammation after TAC surgery and promoted M2 macrophage infiltration in the cardiac tissue. MCC950 not only restored fatty acid uptake and utilization by regulating the expression of CD36 and CPT1β but also reduced glucose uptake and oxidation via regulating the expression of GLUT4 and p-PDH. In addition, MCC950 affected the phosphorylation of AKT and AMPK in obese mice with HF. In summary, MCC950 can alleviate HF induced by pressure overload in obese mice via improving cardiac metabolism, providing a basis for the clinical application of NLRP3 inhibitors in obese patients with HF.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    URL: Article
    DOI: 10.3389/fcvm.2022.727474
    DOI: 10.3389/fcvm.2022.727474.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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