JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2025
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IF 3.1
Zhao-liang Hu,Wen-yu Zou,Peng-wei Hu,Ke-ran Chen,Jia-ying Liu,Jie Deng,Ju-cui Yang,Min Song,Yu-ting Lu,Tai-jun Hang
Letrozole, a nonsteroidal aromatase inhibitor of the triazole class, is widely used in breast cancer treatment. Its quality and stability directly influence therapeutic efficacy and safety. However, systematic characterization of its related substances (RSs) remains insufficiently documented. In this study, letrozole RSs were separated by an established HPLC-UV method and identified with LC-Q-TOF/MS determination following the ICH Q1A(R2) guidelines. 27 RSs were detected, including 11 process-related impurities and 16 previously unreported degradation products. Structural elucidation and degradation pathway analysis were performed for all the RSs by using their chromatographic retention behaviors, DAD spectral features, and high-resolution mass spectrometric data. Three main degradation pathways were proposed for them, including substitution on the triazole ring, hydrolysis of the cyano groups, and oxidation of the benzyl moiety. Furthermore, to support impurity risk assessment, the genotoxicities of all the RSs were evaluated using in-silico models according to the ICH M7 (R2) guideline. Most of the RSs were evaluated to be non-mutagenic, however four of them were identified as structurally alerting. These findings contribute to a better understanding of the stability behavior of letrozole and provide a scientific basis for the drug quality risk management from its related substances test and control point of view.
研究领域:
药物化学
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分析化学
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药学
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DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
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2021
·Vol. 45
·期 5
·e13723
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IF 2.72
Yanyuan Zhou,Huan Lan,Zhewen Dong,Wenjing Cao,Zhen Zeng,Jia-Le Song
This study investigated the effects of proanthocyanidins (PCs) on ovarian fibrosis in letrozole-induced polycystic ovary syndrome (PCOS) in rats. The administration of PCs effectively reduced the body weight (BW) and relative ovarian weight in PCOS rats. ELISA results revealed that PCs significantly reduced the level of serum T, LH, LH/FSH in the PCOS group. In addition, qRT-PCR results revealed that treatment with PCs significantly increased the main antioxidant enzymes (Cat, Sod2, Gpx3, Mgst1, Gsta4, Sod1 and Prdx3) in PCOS rats. Also, the expression analysis of proteins by Western blotting revealed that PCs significantly decreased the level of TGF-βR1, p-Smad3, p-Smad2 and Smad4 and reversed the downregulation of Smad7 in PCOS rats. The study suggested that PCs improved ovarian fibrosis in PCOS rats by regulating the serum hormone level, inhibiting oxidative stress and suppressing the activation of the TGF-β1/Smads signaling pathway. Practical applications Currently, plant extracts are being widely used to treat female reproductive and metabolic disorders. Particularly, proanthocyanidins (PCs), the well-known natural polyphenolic compounds, which are a significant source of antioxidants present in many colored fruits, are consumed as fruits as well as a dietary supplement to prevent many disorders. Recent pharmacological studies have reported that PCs have many health beneficial properties, such as antioxidant activity, improving cholesterol homeostasis, blood lipid regulatory properties, microcirculation improvement effect, antitumor activity and anti-aging activity. Despite these properties of PCs, the antifibrosis effect of PCs has not been studied to date. The main purpose of this study was to research the role and the mechanisms of PCs in ovarian fibrosis in PCOS rats.
研究领域:
药理学
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生殖生物学
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内分泌学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Xiao-yu Xu,Jing Chen,Zhong-xi Chen,Zhe-yan Zhang,Le-hao Jin,Jian-chao Luo,Yun-shan Zhong,Qi Zhou,Jian-chang Qian
The interindividual variability of CYP3A4 activity complicates precision pharmacotherapy, particularly for drugs with narrow therapeutic windows. To explore the relationship between CYP3A4 polymorphisms and metabolic phenotypes, this study used abemaciclib as a probe substrate within a translational framework. The in vitro platform combined a reconstituted enzyme catalysis system for high-throughput inhibitor screening with UPLC-MS/MS metabolic profiling. In vivo pharmacokinetic studies were performed in female SD rats, with optimized sampling during the elimination phase. Human CYP3A4 baculosomes were engineered using baculovirus-mediated expression in Sf21 cells to investigate genetic influences on metabolic variability. Molecular docking and dynamics simulations were also performed to investigate structural differences in inhibitory activity. Results showed that letrozole significantly inhibited CYP3A4-mediated abemaciclib metabolism, reduced its clearance and increased its area under the blood concentration-time curve (AUC) and maximum blood concentration (C max ) through mixed inhibition. Moreover, CYP3A4 polymorphisms substantially impacted abemaciclib pharmacokinetics. Kinetic simulations revealed that the CYP3A4.28 variant formed a stable complex with letrozole, enhancing inhibition, while the CYP3A4.30 variant lost catalytic activity. These findings underscored the critical role of CYP3A4 activity and genetic polymorphisms in drug metabolism and highlighted the necessity for personalized treatment approaches.
研究领域:
药理学
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分子生物学
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遗传学
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临床医学
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DOI
PubMed
高影响因子
TALANTA
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2025
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IF 6.1
Panjie Li,Jiaxin Chen,Yalin Xie,Caijun Wu,Yan Zhao,Xiaojun Luo
Surface-enhanced Raman spectroscopy (SERS), an ultrasensitive molecular fingerprinting technique, requires substrates that synergistically integrate electromagnetic field amplification (via plasmonic hotspots) and analyte enrichment (through nanoscale molecular confinement). Although metal nanoparticles (NPs) generate hotspots, their practical utility is hindered by chemical instability, poor reproducibility, and weak analyte affinity. Covalent organic frameworks (COFs), with designable porosity, ultrahigh surface areas, and stability, offer a promising platform to address these limitations. By combining COFs with noble metals, the molecular enrichment capability of COFs and the plasmonic effects of metals can be synergistically exploited. However, conventional synthesis strategies (chemical reduction, pre-synthesis anchoring) suffer from complex multi-step processes, reducing agent dependence, and irregular deposition of metal NPs on the COF matrix, which compromise SERS performance. Our study proposed a sulfur-rich COF leveraging Au–S soft acid-base interactions to achieve in situ reduction of Au 3+ to Au 0 within COF matrices. Three synthesis approaches−chemical reduction, physical adsorption, and in-situ reduction−were systematically compared, with the in-situ method demonstrating superior SERS enhancement and reproducibility due to the confinement of large-area and high-density NPs. The optimized COF/Au composite enabled ultrasensitive detection of letrozole at 6.07 × 10 −8 g/mL, leveraging COF-inherent Raman peaks for internal calibration. This work provides an innovative solution for developing next-generation SERS sensors with acceptable sensitivity, anti-interference capability, and reproducibility.
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高影响因子
Biomaterials Research
·
2023
·Vol. 27
·期 1
·1-16
·
IF 11.3
Tian Wei,Wang Chenyu,Chu Ran,Ge Haiyan,Sun Xiao,Li Mingjiang
Background Endometriosis is a common gynecological disease in women of childbearing age. Commonly used treatment methods, such as endocrine and surgical therapies, display poor therapeutic effects with a high relapse probability. Thus, novel treatments for endometriosis are required. Methods In our study, polydopamine (PDA), letrozole (LTZ), and agarose (AG) hydrogels were combined to construct an injectable hydrogel with near-infrared controlled drug delivery named LTZ-PDA@AG hydrogel for endometriosis treatment. The release of letrozole can be accurately controlled by the near-infrared light intensity, exposure duration, polydopamine concentration, and hydrogel composition. Meanwhile, we isolated endometrial stromal cells from endometrium in patients with endometriosis, and constructed the rats’ model of endometriosis to verify the biological effects of LTZ-PDA@AG hydrogel. Results Owing to the sufficiently deep penetration of near-infrared light, the LTZ-PDA@AG hydrogel displayed a high temperature increase for efficient photothermal therapy. In addition, high local temperatures can further enhance the diffusion and penetration of letrozole, thereby achieving excellent therapeutic effect in vivo. Importantly, the in vivo and vitro test demonstrated the capacity of the nanocomposite hydrogel for endocrine-photothermal synergistic therapy and the biocompatibility. Conclusion Our work proposes a novel concept for precision endometriosis therapy by photothermal-enhanced endocrine therapy for endometriosis, which is proposed for the first time for the treatment of endometriosis and demonstrates excellent potential for further clinical translation. Trial registration Not applicable. Graphical Abstract LTZ-PDA@AG hydrogels were synthesized and displayed a high temperature increase for efficient photothermal therapy under NIR. The present study shows the capacity of the nanocomposite hydrogel for endocrine-photothermal synergistic therapy and the biocompatibility.
研究领域:
妇科学
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生物医学工程
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纳米技术
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药学
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DOI
PubMed
高影响因子
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