VIBRATIONAL SPECTROSCOPY
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2023
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IF 2.5
Xinyu Cheng,Xiuzhi Chen,Chengfeng Liang,Hongjun Jin,Shizhao Ren,Rongrong Xue,Fenghua Chen
Bicalutamide (BIC) is one fluorine-containing drug with poor aqueous solubility, and it is essential to study the polymorphism of BIC, especially the metastable polymorphs and amorphous phase, to improve the oral effect. Selective crystallizations of BIC amorphous phases and solutions were studied and further explained and predicted by using mid-frequency Raman difference spectra (MFRDS) here. The relationships among various polymorphs and solutions of BIC were established by calculating the values of average deviation (a. d., the average value of absolute value of the intensity of MFRDS) and standard deviation (s. d.) of the MFRDS. And the possible routes to obtain metastable Form II and amorphous BIC were proposed based on the MFRDS results. Metastable Form II can be obtained by recrystallization of the amorphous BIC prepared through melt-quenching method. Amorphous BIC without additives can be prepared through a quicky evaporation process of acetone and ethyl acetate solutions, which was reported for the first time. The MFRDS results confirmed the presence of residual acetone and ethyl acetate in amorphous BIC obtained by evaporation, and the residual solvents changed the recrystallization products of amorphous BIC. MFRDS analysis can be a useful tool to guide the preparation and selective crystallization of metastable polymorphs and amorphous phase.
研究领域:
药学
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材料科学
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产品关联
DOI
高影响因子
JOURNAL OF INORGANIC BIOCHEMISTRY
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2019
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IF 3.224
Jian Zhao,Nannan Liu,Shuchen Sun,Shaohua Gou,Xinyi Wang,Zhimei Wang,Xiaoyan Li,Wenjing Zhang
Targeted delivery of clinically approved anticancer drug to tumor sites is an effective way to achieve enhanced drug efficacy as well as reduced side effects and toxicity. Here bicalutamide is caged by the Ru(II) center through the nitrile group, and three photoactive Ru(II) complexes were designed and synthesized. Docking study showed that the ruthenium(II) fragments can effectively block the binding of complexes 1–3 with AR (androgen receptor) owing to the large steric structures , thus bicalutamide in complexes 1–3 could not interact with AR-LBD (ligand binding domain). Once irradiation with blue light (465 nm), complexes 1–3 can release bicalutamide and anticancer Ru(II) fragments, which possesses dual-action of AR binding and DNA interaction simultaneously. In vitro cytotoxicity study on these complexes further confirmed that complexes 1–3 exhibited considerable cytotoxicity upon irradiation with blue light. Significantly, complex 3 could be activated at 660 nm, which greatly increases the scope of complex 3 to treat deeper within tissue. Theoretical calculations showed that the lowest singlet excitation energy of complex 3 is lower than those of complexes 1–2 , which explains the experimental results well. Moreover, the 3 MC (metal centered) states of these complexes are more stable than their 3 MLCT (metal to ligand charge transfer) states, indicating that the photoactive processes of these complexes are likely to result in ligand dissociation.
研究领域:
化学
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药学
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肿瘤学
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光化学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2021
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IF 6.53
Danlan Fu,Junfei Huang,Kaitao Li,Yuxin Chen,Ye He,Yang Sun,Yilong Guo,Lijuan Du,Qian Qu,Yong Miao,Zhiqi Hu
Androgenic alopecia (AGA), also known as male pattern baldness, is one of the most common hair loss diseases worldwide. The main treatments of AGA include hair transplant surgery, oral medicines, and LDL laser irradiation, although no treatment to date can fully cure this disease. Animal models play important roles in the exploration of potential mechanisms of disease development and in assessing novel treatments. The present study describes androgen receptor (AR) in C57BL/6 mouse hair follicles that can be activated by dihydrotestosterone (DHT) and translocate to the nucleus. This led to the design of a mouse model of androgen-induced AGA in vivo and in vitro. DHT was found to induce early hair regression, hair miniaturization, hair density loss, and changes in hair morphology in male C57BL/6 mice. These effects of DHT could be partly reversed by the AR antagonist bicalutamide. DHT had similar effects in an ex vivo model of hair loss. Evaluation of histology, organ culture, and protein expression could explain the mechanism by which DHT delayed hair regrowth.
研究领域:
皮肤科
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药理学
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分子生物学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Xueyi Liu,Pei Zhang,Huijia Song,Xiaoshuang Tang,Yi Hao,Yibing Guan,Tie Chong,Sameer Hussain,Ruixia Gao
Prostate cancer is the most common malignancy diagnosed in men. Androgens are directly related to its pathogenesis. Inhibition of the androgen receptor (AR) is considered to be the most promising therapeutic approach for the treatment of prostate cancer. In this study, a new type of pH-responsive dual androgen-blocking nanodrug (FASC MIPs) based on a molecularly imprinted polymer has been designed and synthesized. The nanodrug could selectively sequester testosterone from the prostate tumor through specific molecular imprinting sites and simultaneously deliver the AR inhibitory drug bicalutamide, which ultimately leads to enhanced synergistic therapy of prostate cancer. FASC MIPs demonstrate excellent pH responsiveness in a simulated tumor microenvironment due to the presence of chitosan and significantly inhibit the growth of prostate cancer cells (LNCaP cells) by blocking the G1 phase of cytokinesis. Additionally, the nanodrug also displayed excellent antitumor properties in a xenograft mouse model of prostate cancer without any sign of detrimental effects on healthy tissues and organs. Both in vitro and in vivo studies verified the augmented and synergistic therapeutic effects of FASC MIPs, and the proposed dual-androgen-blocking strategy could explore novel avenues in prostate cancer treatment.
研究领域:
肿瘤学
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药学
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
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2025
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IF 9.6
Ren Yuanyuan,Cui Yue,Wang Zhen,Luo Yizhi,Jin Junchang,Yuan Yiyi,Li Xuan,Zhang Yaning,Cao Nan,Li Xiaofang,Yu Yi,Xiong Yuyan
Gastric cancer (GC) is a prevalent gastrointestinal malignancy in which ferroptosis, mitochondrial dysfunction, and macrophage reprogramming remarkably contribute to disease progression. However, the molecular interplay among these processes in contributing to GC remains poorly understood. In this study, we identified ferroptosis- and mitochondrial dysfunction-related genes (FMDRGs) implicated in GC through bioinformatics analyses. Among them, aldehyde dehydrogenase 3 family member A2 (ALDH3A2) was identified as a key FMDRG significantly downregulated in GC tissues and cell lines. Functional assays revealed that ALDH3A2 overexpression in GC cell lines suppressed proliferation, migration, and invasion while enhancing ferroptosis, effects that were reversed by GPX4 overexpression. ALDH3A2 also impaired the mitochondrial unfolded protein response (UPR mt ) and induced mitochondrial dysfunction. Restoration of UPR mt ameliorated ALDH3A2-induced mitochondrial dysfunction and ferroptosis. Mechanistically, ALDH3A2 impaired UPR mt by downregulating SLC47A1 through blockade of NRF2 nuclear translocation, leading to mitochondrial dysfunction, GPX4 downregulation, lipid peroxidation, and subsequent ferroptosis. Synergistically, ALDH3A2-induced ferroptosis promoted IL-6 release, which drove macrophage polarization toward the M1 phenotype with elevated IL-1β production. This macrophage reprogramming, in turn, inhibited GC cell progression by downregulating PD-L1 expression. Therapeutically, both genistein treatment and ALDH3A2 overexpression significantly attenuated GC progression in vitro and in vivo. These findings elucidate ALDH3A2 as a dual regulator of tumor-intrinsic ferroptosis and tumor-extrinsic immune remodeling in contributing to GC pathogenesis, highlighting its potential as a promising therapeutic target in GC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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