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  • 1
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    Online Resource
    Effect of different PD ‐1 inhibitor combination therapies for unresectable intrahepatic cholangiocarcinoma
    Wiley ; 2023
    In:  Alimentary Pharmacology & Therapeutics Vol. 58, No. 6 ( 2023-09), p. 611-622
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 58, No. 6 ( 2023-09), p. 611-622
    Abstract: Immune checkpoint inhibitor (ICI) combination therapy offers a new option for treatment of unresectable intrahepatic cholangiocarcinoma (uICC). Aim To compare the effect of different anti‐PD‐1 combination therapies as the first‐line treatments for uICC. Methods This study included 318 patients who received chemotherapy alone (Chemo), anti‐PD‐1 plus chemotherapy (ICI‐chemo), anti‐PD‐1 plus targeted therapy (ICI‐target) or anti‐PD‐1 plus targeted therapy and chemotherapy (ICI‐target‐chemo) as first line for uICC from 22 centres in China. The primary endpoint was progression‐free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. Results Patients with ICI‐chemo (median PFS [mPFS], 6.3 months; HR: 0.61, 95% CI: 0.42–0.88; p  = 0.008; median OS [mOS], 10.7 months; HR: 0.61, 95% CI: 0.39–0.94; p  = 0.026), ICI‐target (7.2 months; HR: 0.54, 95% CI: 0.36–0.80; p  = 0.002; 15.8 months; HR: 0.54, 95% CI: 0.35–0.84; p  = 0.006) or ICI‐target‐chemo (6.9 months; HR: 0.65, 95% CI: 0.47–0.90; p  = 0.009; 14.4 months; HR: 0.47, 95% CI: 0.31–0.70; p   〈  0.001) achieved better clinical outcomes than those with Chemo (3.8 months; 9.3 months). ICI‐target was not inferior to ICI‐chemo in survival outcomes (HR for PFS: 0.88, 95% CI: 0.55–1.42; p  = 0.614; HR for OS: 0.89, 95% CI: 0.51–1.55; p  = 0.680). ICI‐target‐chemo yielded similar prognoses as ICI‐chemo (HR for PFS: 1.07, 95% CI: 0.70–1.62; p  = 0.764; HR for OS: 0.77, 95% CI: 0.45–1.31; p  = 0.328) and ICI‐target (HR for PFS: 1.20, 95% CI: 0.77–1.88; p  = 0.413; HR for OS: 0.86, 95% CI: 0.51–1.47; p  = 0.583) but resulted in more adverse events ( p   〈  0.001; p  = 0.010). Multivariable and propensity score analyses supported these findings. Conclusions Among patients with uICC, ICI‐chemo or ICI‐target provided more survival benefits than Chemo while achieving comparable prognoses and fewer adverse events than ICI‐target‐chemo.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    URL: Article
    DOI: 10.1111/apt.v58.6
    DOI: 10.1111/apt.17623
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2003094-0
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  • 2
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    Quantitative Identification of Compound‐Dependent On‐Modules and Differential Allosteric Modules From Homologous Ischemic Networks
    Wiley ; 2016
    In:  CPT: Pharmacometrics & Systems Pharmacology Vol. 5, No. 10 ( 2016-10), p. 575-584
    Details
    In: CPT: Pharmacometrics & Systems Pharmacology, Wiley, Vol. 5, No. 10 ( 2016-10), p. 575-584
    Type of Medium: Online Resource
    ISSN: 2163-8306 , 2163-8306
    URL: Issue
    URL: Article
    DOI: 10.1002/psp4.v5.10
    DOI: 10.1002/psp4.12127
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2697010-7
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  • 3
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    Chloroquine is a potent pulmonary vasodilator that attenuates hypoxia‐induced pulmonary hypertension
    Wiley ; 2017
    In:  British Journal of Pharmacology Vol. 174, No. 22 ( 2017-11), p. 4155-4172
    Details
    In: British Journal of Pharmacology, Wiley, Vol. 174, No. 22 ( 2017-11), p. 4155-4172
    Abstract: Sustained pulmonary vasoconstriction and excessive pulmonary vascular remodelling are two major causes of elevated pulmonary vascular resistance in patients with pulmonary arterial hypertension. The purpose of this study was to investigate whether chloroquine induced relaxation in the pulmonary artery (PA) and attenuates hypoxia‐induced pulmonary hypertension (HPH). Experimental Approach Isometric tension was measured in rat PA rings pre‐constricted with phenylephrine or high K + solution. PA pressure was measured in mouse isolated, perfused and ventilated lungs. Fura‐2 fluorescence microscopy was used to measure cytosolic free Ca 2+ concentration levels in PA smooth muscle cells (PASMCs). Patch‐clamp experiments were performed to assess the activity of voltage‐dependent Ca 2+ channels (VDCCs) in PASMC. Rats exposed to hypoxia (10% O 2 ) for 3 weeks were used as the model of HPH or Sugen5416/hypoxia (SuHx) for in vivo experiments. Key Results Chloroquine attenuated agonist‐induced and high K + ‐induced contraction in isolated rat PA. Pretreatment with l ‐NAME or indomethacin and functional removal of endothelium failed to inhibit chloroquine‐induced PA relaxation. In PASMC, extracellular application of chloroquine attenuated store‐operated Ca 2+ entry and ATP‐induced Ca 2+ entry. Furthermore, chloroquine also inhibited whole‐cell Ba 2+ currents through VDCC in PASMC. In vivo experiments demonstrated that chloroquine treatment ameliorated the HPH and SuHx models. Conclusions and Implications Chloroquine is a potent pulmonary vasodilator that may directly or indirectly block VDCC, store‐operated Ca 2+ channels and receptor‐operated Ca 2+ channels in PASMC. The therapeutic potential of chloroquine in pulmonary hypertension is probably due to the combination of its vasodilator, anti‐proliferative and anti‐autophagic effects.
    Type of Medium: Online Resource
    ISSN: 0007-1188 , 1476-5381
    URL: Issue
    URL: Article
    DOI: 10.1111/bph.v174.22
    DOI: 10.1111/bph.13990
    Language: English
    Publisher: Wiley
    Publication Date: 2017
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  • 4
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    Sirtuin 3‐mediated deacetylation of acyl‐ CoA synthetase family member 3 by protocatechuic acid attenuates non‐alcoholic fatty liver disease
    Wiley ; 2020
    In:  British Journal of Pharmacology Vol. 177, No. 18 ( 2020-09), p. 4166-4180
    Details
    In: British Journal of Pharmacology, Wiley, Vol. 177, No. 18 ( 2020-09), p. 4166-4180
    Abstract: Hepatic fatty acid metabolism disorder, a key pathogenic mechanism underlying non‐alcoholic fatty liver disease (NAFLD), is associated with the hyperacetylation of mitochondrial enzymes. Acyl‐CoA synthetase family member 3 (ACSF3), which is involved in the regulation of fatty acid metabolism, was predicted to contain lysine acetylation sites related to the mitochondrial deacetylase sirtuin 3 (SIRT3). The purpose of this study was to explore the underlying mechanism by which SIRT3 deacetylates ACSF3 in NAFLD and the protective effect of the natural phenolic compound protocatechuic acid (PCA) against fatty acid metabolism disorder via the SIRT3/ACSF3 pathway. Experimental Approach The role of protocatechuic acid and its molecular mechanism in NAFLD were detected in rats and SIRT3‐knockout mice fed a high‐fat diet (HFD) and in AML‐12 cells treated with palmitic acid (PA). Key Results Pharmacological treatment with protocatechuic acid significantly attenuated high‐fat diet‐induced fatty acid metabolism disorder in NAFLD. Molecular docking assays showed that protocatechuic acid specifically bound SIRT3 as a substrate and increased SIRT3 protein expression. However, the protective role of protocatechuic acid was abolished by SIRT3 knockdown, which increased ACSF3 expression and exacerbated fatty acid metabolism disorder. Mechanistically, SIRT3 was shown to specifically regulate the acetylation and degradation of ACSF3, which govern the capacity of ACSF3 to mediate fatty acid metabolism disorder during NAFLD. Conclusion and Implications SIRT3‐mediated ACSF3 deacetylation is a novel molecular mechanism in NAFLD therapy and protocatechuic acid confers protection against high‐fat diet‐ and palmitic acid‐induced hepatic fatty acid metabolism disorder through the SIRT3/ACSF3 pathway.
    Type of Medium: Online Resource
    ISSN: 0007-1188 , 1476-5381
    URL: Issue
    URL: Article
    DOI: 10.1111/bph.v177.18
    DOI: 10.1111/bph.15159
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 5
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    ASSOCIATIONS BETWEEN 45T/G POLYMORPHISM OF THE ADIPONECTIN GENE AND PLASMA ADIPONECTIN LEVELS WITH TYPE 2 DIABETES
    Wiley ; 2007
    In:  Clinical and Experimental Pharmacology and Physiology Vol. 34, No. 12 ( 2007-12), p. 1287-1290
    Details
    In: Clinical and Experimental Pharmacology and Physiology, Wiley, Vol. 34, No. 12 ( 2007-12), p. 1287-1290
    Abstract: The purpose of the present study was to investigate the association between the single nucleotide polymorphism (SNP) 45T/G and plasma adiponectin levels and the prevalence of Type 2 diabetes mellitus (T2DM) in Uygurs of the Xinjiang region, China. We performed a cross‐sectional survey in a representative sample of 151 Uygur adults aged 24–80 years. The polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) method was used to determine the distribution of allele and genotype frequency of the SNP45 T/G polymorphism (exon 2) in the adiponectin gene. An ELISA was used to determine plasma adiponectin levels. Logistic regression was used to screen risk factors for T2DM. Compared with the normal glucose tolerance (NGT) group, the T2DM group exhibited a higher distribution of the TG + GG genotype, G allele frequency and lower plasma adiponectin concentrations in TG + GG genotype carriers compared with those with the TT genotype. Compared with SNP45 T carriers, in the NGT group, G carriers had higher levels of systolic and diastolic blood pressure, low density lipoprotein ( P   〈  0.05) and total cholesterol ( P   〈  0.005). In the T2DM group, G carriers had lower levels of homeostasis model assessment (HOMA) of insulin sensitivity ( P   〈  0.05) and higher levels of HOMA of insulin resistance ( P   〈  0.05). Adiponectin SNP 45 is positively correlated with the prevalence of T2DM in Uygurs of Xinjiang. The G allele carriers who have reduced plasma concentrations of adiponectin may have associated insulin resistance.
    Type of Medium: Online Resource
    ISSN: 0305-1870 , 1440-1681
    URL: Issue
    URL: Article
    DOI: 10.1111/cep.2007.34.issue-12
    DOI: 10.1111/j.1440-1681.2007.04713.x
    Language: English
    Publisher: Wiley
    Publication Date: 2007
    detail.hit.zdb_id: 2020033-X
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  • 6
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    Synthesis and evaluation of anticonvulsant activities of 7‐phenyl‐4,5,6,7‐tetrahydrothieno[3,2‐ b ]pyridine derivatives
    Wiley ; 2019
    In:  Archiv der Pharmazie Vol. 352, No. 10 ( 2019-10)
    Details
    In: Archiv der Pharmazie, Wiley, Vol. 352, No. 10 ( 2019-10)
    Abstract: A series of 7‐phenyl‐4,5,6,7‐tetrahydrothieno[3,2‐ b ]pyridine derivatives containing triazole and other heterocycle substituents (methyltriazole, tetrazole, and triazolone) is described. Two experimental methods, maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ), were used to evaluate the anticonvulsant activity of the target compounds. Moreover, the neurotoxicity (NT) was tested using the Rotarod test. 5‐(4‐Chlorophenyl)‐4,5‐dihydrothieno[2,3‐ e ][1,2,4] triazolo[4,3‐ a ]pyridine ( 6c ) showed the best anticonvulsant activity. In the MES and PTZ experiments, the 50% effective dose (ED 50 ) values of compound 6c were 9.5 and 20.5 mg/kg, respectively. From the therapeutic index (PI) values, 6c (MES and PTZ with PI values of 48.0 and 22.2, respectively) showed better safety than the clinical drugs carbamazepine (MES with PI value of 6.4) and ethosuximide (PTZ with PI value of 3.2). The biological activities of the compounds were verified by using molecular docking studies. Compound 6c showed significant interactions with residues at the benzodiazepine‐binding site on gamma‐aminobutyric acid A (GABA A ) receptors. The results of in vivo GABA estimation and bicuculline‐induced seizures showed that 6c may have an effect on the GABA system. The physicochemical and pharmacokinetic properties of the target compounds were predicted.
    Type of Medium: Online Resource
    ISSN: 0365-6233 , 1521-4184
    URL: Issue
    URL: Article
    DOI: 10.1002/ardp.v352.10
    DOI: 10.1002/ardp.201900106
    Language: English
    Publisher: Wiley
    Publication Date: 2019
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  • 7
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    Antioxidant peptides, the guardian of life from oxidative stress
    Wiley ; 2023
    In:  Medicinal Research Reviews
    Details
    In: Medicinal Research Reviews, Wiley
    Abstract: Reactive oxygen species (ROS) are produced during oxidative metabolism in aerobic organisms. Under normal conditions, ROS production and elimination are in a relatively balanced state. However, under internal or external environmental stress, such as high glucose levels or UV radiation, ROS production can increase significantly, leading to oxidative stress. Excess ROS production not only damages biomolecules but is also closely associated with the pathogenesis of many diseases, such as skin photoaging, diabetes, and cancer. Antioxidant peptides (AOPs) are naturally occurring or artificially designed peptides that can reduce the levels of ROS and other pro‐oxidants, thus showing great potential in the treatment of oxidative stress‐related diseases. In this review, we discussed ROS production and its role in inducing oxidative stress‐related diseases in humans. Additionally, we discussed the sources, mechanism of action, and evaluation methods of AOPs and provided directions for future studies on AOPs.
    Type of Medium: Online Resource
    ISSN: 0198-6325 , 1098-1128
    URL: Article
    DOI: 10.1002/med.21986
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2001841-1
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  • 8
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    Investigation of the phase diagrams of chiral praziquantel
    Wiley ; 2006
    In:  Chirality Vol. 18, No. 4 ( 2006-01), p. 259-264
    Details
    In: Chirality, Wiley, Vol. 18, No. 4 ( 2006-01), p. 259-264
    Abstract: In the present work, thermal properties of praziquantel, including melting point phase diagram and solubility, were determined for the purpose of exploration on an integrated enantioseparation process of chromatography and crystallization. The solubility of racemic praziquantel in methanol and 2‐propanol was measured in the temperature range between 0 and 40°C. In agreement with previous conclusions, the resulting phase diagram reveals the racemic compound behavior of praziquantel arising from the existence of eutectics. A ternary phase diagram of praziquantel enantiomers and the methanol system was also determined. Based on the information provided by the ternary solubility phase diagram, an optimized integrated enantioseparation process was suggested. Pure praziquantel crystals were recovered, and the crystal structure was solved by X‐ray crystallography. Chirality, 2006. © 2006 Wiley‐Liss, Inc.
    Type of Medium: Online Resource
    ISSN: 0899-0042 , 1520-636X
    URL: Issue
    URL: Article
    DOI: 10.1002/chir.v18:4
    DOI: 10.1002/chir.20251
    Language: English
    Publisher: Wiley
    Publication Date: 2006
    detail.hit.zdb_id: 2001237-8
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  • 9
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    Shikonin inhibits maturation of bone marrow-derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma : Shikonin inhibits airway inflammation
    Wiley ; 2010
    In:  British Journal of Pharmacology Vol. 161, No. 7 ( 2010-12), p. 1496-1511
    Details
    In: British Journal of Pharmacology, Wiley, Vol. 161, No. 7 ( 2010-12), p. 1496-1511
    Type of Medium: Online Resource
    ISSN: 0007-1188
    URL: Article
    DOI: 10.1111/j.1476-5381.2010.00972.x
    Language: English
    Publisher: Wiley
    Publication Date: 2010
    detail.hit.zdb_id: 2029728-2
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  • 10
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    Nemonoxacin dosage adjustment in patients with severe renal impairment based on population pharmacokinetic and pharmacodynamic analysis
    Wiley ; 2021
    In:  British Journal of Clinical Pharmacology Vol. 87, No. 12 ( 2021-12), p. 4636-4647
    Details
    In: British Journal of Clinical Pharmacology, Wiley, Vol. 87, No. 12 ( 2021-12), p. 4636-4647
    Abstract: To optimize the dosing regimen in patients with severe renal impairment based on population pharmacokinetic (PPK)/pharmacodynamic analysis. Methods The pharmacokinetics and safety of nemonoxacin was evaluated in a single‐dose, open‐label, nonrandomized, parallel‐group study after single oral dose of a 0.5‐g nemonoxacin capsule in 10 patients with severe renal impairment and 10 healthy controls. Both blood and urine samples were collected within 72 hours after admission and determined the concentrations. A PPK model was built using nonlinear mixed effects modelling. The probability of target attainment and the cumulative fraction of response against Streptococcus pneumoniae and Staphylococcus aureus was calculated by Monte Carlo simulation. Results The data best fitted a 2‐compartment model, from which the PPK parameters were estimated, including clearance (8.55 L/h), central compartment volume (80.8 L) and peripheral compartment volume (50.6 L). The accumulative urinary excretion was 23.4 ± 6.5% in severe renal impairment patients and 66.1 ± 16.8% in healthy controls. PPK/pharmacodynamic modelling and simulation of 4 dosage regimens found that nemonoxacin 0.5 g every 48 hours (q48h) was the optimal dosing regimen in severe renal impairment patients, evidenced by higher probability of target attainment (92.7%) and cumulative fraction of response ( 〉 99%) at nemonoxacin minimum inhibitory concentration ≤ 1 mg/L against S. pneumoniae and S. aureus . The alternative regimens (0.25 g q24h; loading dose 0.5 g on Day 1 followed by 0.25 g q24h) were insufficient to cover the pathogens even if minimum inhibitory concentration = 1 mg/L. Conclusion An extended dosing interval (0.5 g q48h) may be appropriate for optimal efficacy of nemonoxacin in case of severe renal impairment.
    Type of Medium: Online Resource
    ISSN: 0306-5251 , 1365-2125
    URL: Issue
    URL: Article
    DOI: 10.1111/bcp.v87.12
    DOI: 10.1111/bcp.14881
    RVK:
    XA 33650
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1498142-7
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