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  • Frontiers Media SA  (18)
  • Pharmacy  (18)
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  • Pharmacy  (18)
  • 1
    Online Resource
    Online Resource
    DataSheet1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-8-12)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-8-12)
    Abstract: Forsythiae Fructus (FF), the fruit of Forsythia suspensa (Thunb.) Vahl. (Lianqiao), is one of the most fundamental herbs in Traditional Chinese Medicines (TCM), mainly due to its heat-clearing and detoxifying effects. There are two types of FF, the greenish fruits that start to ripen (GF) and the yellow fruits that are fully ripe (RF), called “Qingqiao” and “Laoqiao” referred to the Chinese Pharmacopoeia, respectively. It undergoes a complex series of changes during the maturation of FF. However, the clinical uses and preparation of phytopharmaceuticals of FF have not been distinguished to date. Moreover, there is limited information on the study of the difference in pharmacological activity between RF and GF. In this study, a rat model of bile duct ligation (BDL)-induced cholestasis was used to compare the differences in their effects. RF was found to have better results than GF in addressing toxic bile acids (BAs) accumulation and related pathological conditions caused by BDL. The underlying mechanism may be related to the interventions of gut microbiota. The results of the present study suggest that the better detoxifying effect of RF than GF may be indirectly exerted through the regulation of gut microbiota and thus the improvement of BAs metabolism.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.987695
    DOI: 10.3389/fphar.2022.987695.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
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  • 2
    Online Resource
    Online Resource
    A Risk-Factor Model for Antineoplastic Drug-Induced Serious Adverse Events in Cancer Inpatients: A Retrospective Study Based on the Global Trigger Tool and Machine Learning
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-6-29)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-6-29)
    Abstract: The objective of this study was to apply a machine learning method to evaluate the risk factors associated with serious adverse events (SAEs) and predict the occurrence of SAEs in cancer inpatients using antineoplastic drugs. A retrospective review of the medical records of 499 patients diagnosed with cancer admitted between January 1 and December 31, 2017, was performed. First, the Global Trigger Tool (GTT) was used to actively monitor adverse drug events (ADEs) and SAEs caused by antineoplastic drugs and take the number of positive triggers as an intermediate variable. Subsequently, risk factors with statistical significance were selected by univariate analysis and least absolute shrinkage and selection operator (LASSO) analysis. Finally, using the risk factors after the LASSO analysis as covariates, a nomogram based on a logistic model, extreme gradient boosting (XGBoost), categorical boosting (CatBoost), adaptive boosting (AdaBoost), light-gradient-boosting machine (LightGBM), random forest (RF), gradient-boosting decision tree (GBDT), decision tree (DT), and ensemble model based on seven algorithms were used to establish the prediction models. A series of indicators such as the area under the ROC curve (AUROC) and the area under the PR curve (AUPR) was used to evaluate the model performance. A total of 94 SAE patients were identified in our samples. Risk factors of SAEs were the number of triggers, length of stay, age, number of combined drugs, ADEs occurred in previous chemotherapy, and sex. In the test cohort, a nomogram based on the logistic model owns the AUROC of 0.799 and owns the AUPR of 0.527. The GBDT has the best predicting abilities (AUROC = 0.832 and AUPR = 0.557) among the eight machine learning models and was better than the nomogram and was chosen to establish the prediction webpage. This study provides a novel method to accurately predict SAE occurrence in cancer inpatients.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2022.896104
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
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  • 3
    Online Resource
    Online Resource
    DataSheet2.DOCX
    Frontiers Media SA ; 2023
    In:  Frontiers in Pharmacology Vol. 14 ( 2023-10-10)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 14 ( 2023-10-10)
    Abstract: Background: The Zhuyu pill (ZYP), composed of Coptis chinensis Franch. and Tetradium ruticarpum (A. Jussieu) T. G. Hartley, is an effective traditional Chinese medicine with potential anti-cholestatic effects. However, the underlying mechanisms of ZYP remain unknown. Objective: To investigate the mechanism underlying the interventional effect of ZYP on mRNA-seq analysis in cholestasis rat models. Materials and methods: This study tested the effects of a low-dose (0.6 g/kg) and high-dose (1.2 g/kg) of ZYP on a cholestasis rat model induced by α-naphthyl-isothiocyanate (ANIT, 50 mg/kg). Serum biochemistry and histopathology results were used to evaluate the therapeutic effect of ZYP, and mRNA-Seq analysis was performed and verified using real-time fluorescence quantitative PCR (qRT-PCR). GO, KEGG, and GSEA analyses were integrated to identify the mechanism by which ZYP impacted cholestatic rats. Results: ZYP was shown to significantly improve abnormal changes in the biochemical blood indexes and liver histopathology of cholestasis rats and regulate pathways related to bile and lipid metabolism, including fatty acid metabolism, retinol metabolism, and steroid hormone biosynthesis, to alleviate inflammation, cholestasis, and lipid metabolism disorders. Relative expression of the essential genes Cyp2a1, Ephx2, Acox2, Cyp1a2, Cyp2c11, and Sult2a1 was verified by qRT-PCR and showed the same trend as mRNA-seq analysis. Conclusion: ZYP has a significant anti-cholestatic effect by regulating bile metabolism and lipid metabolism related pathways. These findings indicate that ZYP is a novel and promising prospect for treating cholestasis.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2023.1280864
    DOI: 10.3389/fphar.2023.1280864.s001
    DOI: 10.3389/fphar.2023.1280864.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
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  • 4
    Online Resource
    Online Resource
    Table1.DOCX
    Frontiers Media SA ; 2023
    In:  Frontiers in Pharmacology Vol. 14 ( 2023-2-8)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 14 ( 2023-2-8)
    Abstract: Introduction: Bu-Fei-Huo-Xue capsule (BFHX) has been used to treat pulmonary fibrosis (PF) in clinic. However, the mechanism of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis remains unclear. Recent studies have shown that the changes in gut microbiota were closely related to the progression of pulmonary fibrosis. Modulating gut microbiota provides new thoughts in the treatment of pulmonary fibrosis. Methods: In this study,a mouse model of pulmonary fibrosis was induced using bleomycin (BLM) and treated with Bu-Fei-Huo-Xue capsule. We firstly evaluated the therapeutic effects of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis model mice. Besides,the anti-inflammatory and anti- oxidative effects of Bu-Fei-Huo-Xue capsule were evaluated. Furthermore, 16S rRNA sequencing was used to observe the changes in gut microbiota in pulmonary fibrosis model mice after Bu-Fei-Huo-Xue capsule treatment. Results: Our results showed that Bu-Fei-Huo-Xue capsule significantly reduced the collagen deposition in pulmonary fibrosis model mice. Bu-Fei-Huo-Xue capsule treatment also reduced the levels and mRNA expression of pro-inflammatory cytokines and inhibited the oxidative stress in lung. 16S rRNA sequencing showed that Bu-Fei-Huo-Xue capsule affected the diversity of gut microbiota and the relative abundances of gut microbiota such as Lactobacillus , Lachnospiraceae _NK4A136_group, and Romboutsia . Conclusion: Our study demonstrated the therapeutic effects of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis. The mechanisms of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis may be associated with regulating gut microbiota.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2023.1084617
    DOI: 10.3389/fphar.2023.1084617.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
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  • 5
    Online Resource
    Online Resource
    Structures of the SARS-CoV-2 spike glycoprotein and applications for novel drug development
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-8-9)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-8-9)
    Abstract: COVID-19 caused by SARS-CoV-2 has raised a health crisis worldwide. The high morbidity and mortality associated with COVID-19 and the lack of effective drugs or vaccines for SARS-CoV-2 emphasize the urgent need for standard treatment and prophylaxis of COVID-19. The receptor-binding domain (RBD) of the glycosylated spike protein (S protein) is capable of binding to human angiotensin-converting enzyme 2 (hACE2) and initiating membrane fusion and virus entry. Hence, it is rational to inhibit the RBD activity of the S protein by blocking the RBD interaction with hACE2, which makes the glycosylated S protein a potential target for designing and developing antiviral agents. In this study, the molecular features of the S protein of SARS-CoV-2 are highlighted, such as the structures, functions, and interactions of the S protein and ACE2. Additionally, computational tools developed for the treatment of COVID-19 are provided, for example, algorithms, databases, and relevant programs. Finally, recent advances in the novel development of antivirals against the S protein are summarized, including screening of natural products, drug repurposing and rational design. This study is expected to provide novel insights for the efficient discovery of promising drug candidates against the S protein and contribute to the development of broad-spectrum anti-coronavirus drugs to fight against SARS-CoV-2.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2022.955648
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
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  • 6
    Online Resource
    Online Resource
    Li-Dan-He-Ji Improves Infantile Cholestasis Hepatopathy Through Inhibiting Calcium-Sensing Receptor-Mediated Hepatocyte Apoptosis
    Frontiers Media SA ; 2020
    In:  Frontiers in Pharmacology Vol. 11 ( 2020-2-28)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 11 ( 2020-2-28)
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2020.00156
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2587355-6
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  • 7
    Online Resource
    Online Resource
    Sphingosine 1-phosphate Stimulates Insulin Secretion and Improves Cell Survival by Blocking Voltage-dependent K+ Channels in β Cells
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-7-12)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-7-12)
    Abstract: Recent studies suggest that Sphingosine 1-phosphate (S1P) plays an important role in regulating glucose metabolism in type 2 diabetes. However, its effects and mechanisms of promoting insulin secretion remain largely unknown. Here, we found that S1P treatment decreased blood glucose level and increased insulin secretion in C57BL/6 mice. Our results further showed that S1P promoted insulin secretion in a glucose-dependent manner. This stimulatory effect of S1P appeared to be irrelevant to cyclic adenosine monophosphate signaling. Voltage-clamp recordings showed that S1P did not influence voltage-dependent Ca 2+ channels, but significantly blocked voltage-dependent potassium (Kv) channels, which could be reversed by inhibition of phospholipase C (PLC) and protein kinase C (PKC). Calcium imaging revealed that S1P increased intracellular Ca 2+ levels, mainly by promoting Ca 2+ influx, rather than mobilizing intracellular Ca 2+ stores. In addition, inhibition of PLC and PKC suppressed S1P-induced insulin secretion. Collectively, these results suggest that the effects of S1P on glucose-stimulated insulin secretion (GSIS) depend on the inhibition of Kv channels via the PLC/PKC signaling pathway in pancreatic β cells. Further, S1P improved β cell survival; this effect was also associated with Kv channel inhibition. This work thus provides new insights into the mechanisms whereby S1P regulates β cell function in diabetes.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2021.683674
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 8
    Online Resource
    Online Resource
    TMEM88 Modulates Lipid Synthesis and Metabolism Cytokine by Regulating Wnt/β-Catenin Signaling Pathway in Non-Alcoholic Fatty Liver Disease
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 12 ( 2022-1-4)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2022-1-4)
    Abstract: Objective: To clarify the molecular mechanism of TMEM88 regulating lipid synthesis and metabolism cytokine in NAFLD. Methods: In vivo , NAFLD model mice were fed by a Methionine and Choline-Deficient (MCD) diet. H & amp;E staining and immunohistochemistry experiments were used to analyze the mice liver tissue. RT-qPCR and Western blotting were used to detect the lipid synthesis and metabolism cytokine. In vitro , pEGFP-C1-TMEM88 and TMEM88 siRNA were transfected respectively in free fat acid (FFA) induced AML-12 cells, and the expression level of SREBP-1c, PPAR-α, FASN, and ACOX-1 were evaluated by RT-qPCR and Western blotting. Results: The study found that the secretion of PPAR-α and its downstream target ACOX-1 were upregulated, and the secretion of SREBP-1c and its downstream target FASN were downregulated after transfecting with pEGFP-C1-TMEM88. But when TMEM88 was inhibited, the experimental results were opposite to the aforementioned conclusions. The data suggested that it may be related to the occurrence, development, and end of NAFLD. Additionally, the study proved that TMEM88 can inhibit Wnt/β-catenin signaling pathway. Meanwhile, TMEM88 can accelerate the apoptotic rate of FFA-induced AML-12 cells. Conclusion: Overall, the study proved that TMEM88 takes part in regulating the secretion of lipid synthesis and metabolism cytokine through the Wnt/β-catenin signaling pathway in AML-12 cells. Therefore, TMEM88 may be involved in the progress of NAFLD. Further research will bring new ideas for the study of NAFLD.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2021.798735
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 9
    Online Resource
    Online Resource
    DataSheet1.PDF
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-9-14)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-9-14)
    Abstract: Angiotensin II type 1 (AT1) receptor blockers (ARBs), as antihypertensive drugs, have drawn attention for their benefits to individuals with diabetes and prediabetes. However, the direct effects of ARBs on insulin secretion remain unclear. In this study, we aimed to investigate the insulinotropic effect of ARBs and the underlying electrophysiological mechanism. We found that only telmisartan among the three ARBs (telmisartan, valsartan, and irbesartan) exhibited an insulin secretagogue role in rat islets. Independent of AT1 receptor and peroxisome proliferator-activated receptor γ (PPARγ), telmisartan exerted effects on ion channels including voltage-dependent potassium (Kv) channels and L-type voltage-gated calcium channels (VGCCs) to promote extracellular Ca 2+ influx, thereby potentiating insulin secretion in a glucose-dependent manner. Furthermore, we identified that telmisartan directly inhibited Kv2.1 channel on a Chinese hamster ovary cell line with Kv2.1 channel overexpression. Acute exposure of db/db mice to a telmisartan dose equivalent to therapeutic doses in humans resulted in lower blood glucose and increased plasma insulin concentration in OGTT. We further observed the telmisartan-induced insulinotropic and electrophysiological effects on pathological pancreatic islets or β-cells isolated from db / db mice. Collectively, our results establish an important insulinotropic function of telmisartan distinct from other ARBs in the treatment of diabetes.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2021.739637
    DOI: 10.3389/fphar.2021.739637.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 10
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    Online Resource
    Pregnenolone Inhibits Osteoclast Differentiation and Protects Against Lipopolysaccharide-Induced Inflammatory Bone Destruction and Ovariectomy-Induced Bone Loss
    Frontiers Media SA ; 2020
    In:  Frontiers in Pharmacology Vol. 11 ( 2020-3-27)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 11 ( 2020-3-27)
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2020.00360
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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