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1.
Infect Drug Resist ; 15: 1687-1694, 2022.
Article in English | MEDLINE | ID: mdl-35422642

ABSTRACT

Purpose: The novel coronavirus disease 2019 (COVID-19) epidemic is the severe global pandemic with large numbers of infected cases and deaths in recent decades. The previous studies were all about the influence of albumin (ALB) for the severity and mortality of in-patients infected with COVID-19. But few studies exist about the influence factors to achieve viral negative conversion. Therefore, this study conducted an exploratory study to investigate the effect of albumin on negative conversion rate. Methods: Among the 190 hospitalized patients with moderate COVID-19 who had a course of disease longer than 30 days, 102 achieved viral negative conversion in 30-45 days and 88 not after 45 days. Taking other variables as concomitant variable, Cox proportional hazard regression model was applied to explore the influence of albumin to negative conversion rate under various factors. Results: By comparing patients who could and could not achieve the finally viral negative conversion, a possible nonlinear relationship between the continuous variables and clinical outcomes was examined by a restricted cubic spline regression model. An association was found between albumin levels and hazard ratio of viral negative conversion rate (P = 0.027). The increase of albumin was accompanied with decreases of hazard ratio of viral negative conversion rate (the value of albumin <38 g/L). But when the value of albumin was higher than 38 g/L, the hazard ratio of viral negative conversion rate approached 1, it means that albumin is not a risk factor for the viral negative conversion rate of COVID-19 disease. Conclusion: For patients with COVID-19, albumin is a common and observed laboratory parameter. It is associated with final viral negative conversion rate although its underlying mechanism and relationship with the viral negative conversion rate still need to be clarified.

2.
Yao Xue Xue Bao ; 49(5): 622-6, 2014 May.
Article in Chinese | MEDLINE | ID: mdl-25151731

ABSTRACT

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.


Subject(s)
Antineoplastic Agents/pharmacology , Hypoxia-Inducible Factor 1/metabolism , Lignans/pharmacology , Animals , Breast Neoplasms/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Heterografts , Humans , Mice, Nude
3.
Chem Pharm Bull (Tokyo) ; 61(8): 877-81, 2013.
Article in English | MEDLINE | ID: mdl-23676628

ABSTRACT

Dasatinib was identified as a potent orally administered Src/Abl kinase inhibitor with excellent antiproliferative activity against Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase. The low bioavailability of Dasatinib may be due to both incomplete oral absorption and first-pass metabolism. A prodrug, JLTN, was synthesized to minimize the first-pass effect of Dasatinib and improve the oral bioavailability following oral administration via targeting intestinal peptide transporter and enhancing chemical stability. Biological evaluation data indicated that there was a 150%-fold increase in oral bioavailability of this prodrug compared to the parent drug Dasatinib in monkeys.


Subject(s)
Prodrugs/chemical synthesis , Prodrugs/pharmacokinetics , Pyrimidines/chemical synthesis , Pyrimidines/pharmacokinetics , Thiazoles/chemical synthesis , Thiazoles/pharmacokinetics , Animals , Dasatinib , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Macaca mulatta , Male , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/pharmacokinetics
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