JOURNAL OF MOLECULAR LIQUIDS
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2021
·
IF 6.165
Jiao Sha,Kaibo Hu,Tingting Li,Zidan Cao,Yameng Wan,Renren Sun,Haixia He,Gaoliang Jiang,Yu Li,Tao Li,Baozeng Ren
The equilibrium solubility and thermodynamic properties of flutamide in eleven organic mono-solvents were reported. Solubility determinations were performed through the laser monitoring method at T = (278.15–323.15) K and p = 101.3 kPa (except DMSO at 293.15–323.15 K and dichloromethane at 278.15–308.15 K). It is found that the mole fraction solubility of flutamide increases apparently with the augmented experimental temperature. The solubility of flutamide in mono-solvents exhibits the following order from minimal to maximum: ethanediol < dichloromethane < methanol < ethanol < methyl acetate < ethyl acetate < 2-methoxyethanol < 2-ethoxyethanol < acetone < DMF < DMSO. The highest value in flutamide solubility profile is related to DMSO at 323.15 K ( x 1 = 5.120*10 −3 ) and the lowest one is obtained for ethanediol (8.900*10 −6 , T = 278.15 K). The results of using the KAT-LSER model to study the solvent effect of flutamide solubility show that the solute-solvent interactions are principally attributed to the hydrogen bonding basicity and solvent's self-cohesiveness. Then, the analysis of solute-solvent interactions using MD simulation shows that the interactions between solute and solvent molecules have an important influence on the solubility of flutamide in selected solvents. In addition, all recorded solubility of flutamide was regressed by λh model, modified Apleblat model, Two-Suffix Margules model, NRTL model and UNIQUAC model. The deviation analysis proves that the λh model obtains the best agreement between the measured data and calculated values, with the minimum mean values of 100ARD (0.275) and RMSD (3.703*10 −4 ). Moreover, apparent thermodynamic properties of flutamide in all mono-solvents studied were also calculated and investigated according to Van't Hoff equation, and it turns out that the dissolution process is an endothermic, non-spontaneous process driven by entropy.
研究领域:
药学
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物理化学
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DOI
高影响因子
SAUDI PHARMACEUTICAL JOURNAL
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2016
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IF 2.233
Jinpu Peng,Lianju Shen,Jinjun Chen,Xining Cao,Yue Zhou,Huali Weng,Chunlan Long,Deying Zhang,Shengfen Tu,Yan Zhang,Dawei He,Tao Lin,Guanghui Wei
This study focuses on investigation of cryptorchidism induced by flutamide (Flu) and its histopathological damage, and detects retinoic acid concentration in testicle tissue, in order to find a new method for clinical treatment to infertility caused by cryptorchidism. Twenty SD (Sprague Dawley) pregnant rats were randomly divided into Flu cryptorchidism group ( n = 10) and normal control group ( n = 10). HE stained for observing morphological difference. Transmission electron microscope (TEM) was used for observing the tight junction structure between Sertoli cells. Epididymal caudal sperms were counted and observed in morphology. The expression of stimulated by retinoic acid gene 8 (Stra8) was detected using immunohistochemistry, western blot, and Q-PCR. High performance liquid chromatography (HPLC) analysis was made on retinoic acid content. Sperm count and morphology observation confirmed cryptorchidism group was lower than normal group in sperm quantity and quality. The observation by TEM showed a loose structure of tight junctions between Sertoli cells. Immunohistochemistry, western blot, and Q-PCR showed that cryptorchidism group was significantly lower than normal group in the expression of Stra8. HPLC showed that retinoic acid content was significantly lower in cryptorchid testis than in normal testis. In the cryptorchidism model, retinoic acid content in testicular tissue has a significant reduction; testicles have significant pathological changes; damage exists in the structure of tight junctions between Sertoli cells; Stra8 expression has a significant reduction, perhaps mainly contributing to spermatogenesis disorder.
研究领域:
生殖生物学
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内分泌学
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组织病理学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2021
·
IF 4.36
Yannan Ding,Honghong Ma,Yasha Xu,Feng Yang,Yi Li,Fuguo Shi,Yuanfu Lu
Ethnopharmacological relevance Xian-Ling-Gu-Bao (XLGB) Fufang is herbal formula widely used to treat osteoporosis and other bone disorders. Because of its commonality in the clinical use, there is a safety concern over the use of XLGB combined with other androgen deprivation therapy (ADT) drugs such as flutamide (FLU) that is associated with reduced bone density. To date, there have been no evaluations on the side effects of the drug-drug interaction between XLGB and FLU. Aim of the study The present study was designed to investigate the hepatotoxicity in the context of the combined treatment of XLGB and FLU in a mouse model, and to determine whether the metabolic activation of FLU through induction of CYP1A2 plays a role in the increased hepatoxicity caused by the combination of XLGB and FLU. Materials and methods C57 mice were administered with either XLGB (6,160 mg/kg), FLU (300 mg/kg), or with the combination of the two drugs. Animals were treated with XLGB for 5 days before the combined administration of XLGB and FLU for another 4 days. The serum of mice from single or the combined administration groups was collected for biochemical analysis. The mouse liver was collected to examine liver morphological changes, evaluate liver coefficient, as well as determine the mRNA expression of P450 isozymes ( Cyp1a2 , Cyp3a11 and Cyp2c37 ). For metabolism analysis, mice were treated with XLGB, FLU, or the combination of XLGB and FLU for 24 h. The urine samples were collected for the analysis of FLU-NAC conjugate by UPLC-Q-Orbitrap MS. The liver microsomes were prepared from fresh livers to determine the activity of metabolizing enzyme CYP1A2. Results The combined treatment of XLGB and FLU caused loss of mice body weight and elicited significant liver toxicity as evidenced by an increased liver coefficient and serum lactate dehydrogenase (LDH) activity as well as pathological changes of fatty lesion of liver tissue. FLU increased hepatic expression of Cyp1a2 mRNA that was further elevated in the liver of mice when administered with both FLU and XLGB. Treatment of FLU resulted in an increase in the expression of Cyp3a 11 mRNA that was negated when mice were co-treated with FLU and XLGB. No significant difference in Cyp2c3 7 mRNA expression was observed among the different treatment groups as compared to the control. Analysis of metabolic activity showed that the combined administration caused a synergic effect in elevating the activity of the CYP1A2 enzyme. Mass spectrometry analysis identified the presence of FLU reactive metabolite derived FLU-NAC conjugate in the urine of mice treated with FLU. Strikingly, about a two-fold increase of the FLU-NAC conjugate was detected when treated with both FLU and XLGB, indicating an elevated amount of toxic metabolite produced from FLU in the present of XLGB. Conclusion FLU and XLGB co-treatment potentiated FLU-induced hepatoxicity. This increased hepatoxicity was mediated through the induction of CYP1A2 activity which in turn enhanced bioactivation of FLU leading to over production of FLU-NAC conjugate and oxidative stress. These results offer warnings about serious side effects of the FLU-XLGB interaction in the clinical practice.
研究领域:
药理学
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毒理学
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民族药理学
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DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2025
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IF 4.7
Ning Li,Canfeng Bian,Jia Guo,Yan Gao,Qin Hu,Zhenquan Yang,Lixia Xiao,Tianzhu Guan
Flutamide, a non-steroidal anti-androgen drug, is commonly used in the treatment of prostate cancer. To understand the interaction between flutamide and blood proteins, we investigated its binding mechanism with bovine serum albumin (BSA) using multi-spectroscopic and theoretical analysis methods. Fluorescence quenching experiments revealed that the intrinsic fluorescence of BSA was reduced by the addition of flutamide through a static quenching mechanism. The formation of the BSA-flutamide complex was further confirmed using UV–visible absorption spectroscopy. The binding site number of BSA and flutamide was close to 1, indicating a single binding site between them. Thermodynamic analyses suggested that hydrophobic interactions and hydrogen bonds were the primary driving forces behind the complex formation. Circular dichroism spectroscopy showed minor conformational changes in the secondary structure of BSA upon flutamide binding. Molecular docking revealed that flutamide binds predominantly in a hydrophobic pocket of BSA, forming stable hydrogen bonds with key residues. MD simulations demonstrated that the BSA-Flutamide complex remained stable throughout the 100 ns simulation without significant structural deviations. This comprehensive analysis provides valuable reference material for understanding the interaction between flutamide and BSA during blood transport.
研究领域:
生物化学
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药物化学
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计算生物学
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DOI
PubMed
高影响因子
JOURNAL OF INVESTIGATIVE SURGERY
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2018
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IF 1.122
Yue Zhou,Jinpu Peng,Xining Cao,Chao Yan,Fangyuan Huang,Lianju Shen,Chunlan Long,Xing Liu,Guanghui Wei
Objective: The aim of this study was to identify a theoretical support for the prevention of urethral fistula following hypospadias repair, by comparing the preputial wound healing process in Sprague-Dawley (SD) rats with and without hypospadias induced by flutamide. Methods: Fifteen pregnant SD rats were randomly divided into three groups. These rats in one group received the androgen receptor antagonist flutamide (25 mg/kg/day) from gestation days 11–17, to establish a rat model of hypospadias for further study of the molecular mechanisms of the hypospadias etiology. The pregnant rats in the control groups were not administered flutamide. The pups from the control and experiment groups underwent an incision on the dorsal prepuce on postnatal day 25 and were sacrificed on postoperative days 3, 7, and 14 to collect penis samples. The penis morphology was examined in all groups. Subsequently, transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMactin), and signal transducers and activators of the transcription 3 (STAT3) expression levels in the different groups were measured at the indicated time points postoperatively using qRT-PCR and Western blot. Results: There was less regeneration of the subcutaneous tissue in hypospadias rats than in the sham-operated group (P < 0.05) on postoperative day 3. No differences were found in the regeneration of the subcutaneous tissue between these groups on postoperative days 7 or 14. Additionally, there were no differences in the epithelial cell regeneration between the control and the hypospadias groups at any postoperative timepoint. Moreover, the expression levels of TGF-β1, α-SMactin, and STAT3 were all significantly lower in hypospadias group than that in the sham-operated group (P < 0.05). Conclusion: The results from the present work suggest that preputial wound healing is retarded in rats with hypospadias induced by flutamide and that this retardation might result from multi-gene regulation.
研究领域:
泌尿外科
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分子生物学
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动物模型
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DOI
PubMed
高影响因子
MICROCHIMICA ACTA
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2025
·Vol. 192
·期 9
·1-16
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IF 5.3
Wang Yilin,Li Zhen,Chen Yinzhi,Liu Zhifang,Li Jiejun,Xie Yixi,Li Xinyi,Zhao Pengcheng,Fei Junjie
Ni@carbon nanoframework-multi-walled carbon nanotubes (Ni@CNF-CNTs) nanomaterials were synthesized through the carbonization of flower-like nickel metal organic framework (Ni-MOF) and multi-walled carbon nanotubes (MWCNTs). Subsequently, a high-performance flutamide (FLT) - an anti-androgen drug - electrochemical sensor was constructed using the nanomaterials. Both Ni@carbon nanoframework (Ni@CNF) and MWCNTs have adsorption capacity for FLT. Importantly, the excellent electrical conductivity of MWCNTs, combined with the multiple metal reactive sites of Ni@CNF, enables the synthesized materials to effectively detect the environmental pollutant FLT. The Ni@CNF-CNTs/glassy carbon electrode (Ni@CNF-CNTs/GCE) sensor demonstrates the capability to detect FLT concentrations ranging from 0.1 to 4.9 μM, with a limit of detection (LOD) of 23.2 nM ( S / N = 3). The manufactured sensor is characterized by remarkable stability and selectivity, with recoveries ranging from 96.7% to 101.6% in actual samples. Furthermore, the detection results were validated using ultraviolet–visible spectroscopy (UV–Vis), indicating its applicability for detecting FLT in real environmental water samples. This work presents a novel approach to developing a sensitive, eco-friendly, and cost-effective FLT detection technique, demonstrating the effectiveness of electrochemical sensors. Graphical
研究领域:
分析化学
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环境科学
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纳米技术
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电化学
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传感器技术
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-16
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IF 10.6
Guo Yiming,Wu Jicheng,Chen Lefan,Liu Lujie,Bi Tianxiang,Pan Yuanwei,Meng Qian-Fang,Wang Chaoliang,Rao Lang,Li Qi
Androgen deprivation therapy (ADT) is a crucial and effective strategy for prostate cancer, while systemic administration may cause profound side effects on normal tissues. More importantly, the ADT can easily lead to resistance by involving the activation of NF-κB signaling pathway and high infiltration of M2 macrophages in tumor microenvironment (TME). Herein, we developed a biomimetic nanotherapeutic platform by deriving cell membrane nanovesicles from cancer cells and probiotics to yield the hybrid cellular nanovesicles (hNVs), loading flutamide (Flu) into the resulting hNVs, and finally modifying the hNVs@Flu with Epigallocatechin-3-gallate (EGCG). In this nanotherapeutic platform, the hNVs significantly improved the accumulation of hNVs@Flu-EGCG in tumor sites and reprogramed immunosuppressive M2 macrophages into antitumorigenic M1 macrophages, the Flu acted on androgen receptors and inhibited tumor proliferation, and the EGCG promoted apoptosis of prostate cancer cells by inhibiting the NF-κB pathway, thus synergistically stimulating the antitumor immunity and reducing the side effects and resistance of ADT. In a prostate cancer mouse model, the hNVs@Flu-EGCG significantly extended the lifespan of mice with tumors and led to an 81.78% reduction in tumor growth compared with the untreated group. Overall, the hNVs@Flu-EGCG are safe, modifiable, and effective, thus offering a promising platform for effective therapeutics of prostate cancer. Graphical Abstract
研究领域:
癌症治疗
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纳米技术
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免疫疗法
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药理学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Cell Reports Physical Science
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2025
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IF 7.3
Junrong Lin,Zetao Dang,Yijing Du,Yanli Gao,Jia Li,Yuewei Zhang,Shoujun Zhu
Assessing the integrity of the blood-testis barrier (BTB) is critical, as it serves to protect developing sperm cells by creating a protective environment against toxins and pathogens. Here, we optimize a near-infrared (NIR) dye for in situ binding of endogenous albumin or constructing NIR-II fluorescent proteins (FPs) based on exogenous albumin, affording non-invasive in vivo imaging of BTB disruption with tunable time windows. To further enhance the targeting capability of FPs, we employ a site-directed mutagenesis (SDM) strategy to develop the mutant albumin with increased binding efficiency to CO-1080 at room temperature, which serves as a specialized exogenous albumin for accelerating the imaging window of BTB disruption. Given the common drawbacks of traditional modalities for assessing BTB integrity, non-invasive and real-time NIR-II imaging is an effective method for investigating the testicular microenvironment as well as understanding testicular physiology and pathology.
研究领域:
生物医学工程
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分子影像
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生殖生物学
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产品关联
DOI
高影响因子
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