JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
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2025
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IF 1.8
Jinxingyi Wang,Ruyu Tao,Hanshuai Hu,Xue Lan,Jiejie Gao,Yanping Guan,Qian Liu
Background Busulfan and cyclophosphamide (Bu-Cy) is a widely used conditioning regimen for hematopoietic stem cell transplantation (HSCT) in the treatment of hematologic malignancies. To explore the exposure-efficiency relationships of Bu-Cy regimen and evaluate the necessity of relative therapeutic drug monitoring (TDM), we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to simultaneously quantify the busulfan and cyclophosphamide in human plasma. Methods A simple LC-MS/MS bioassay for simultaneous determination of busulfan and cyclophosphamide using isotope dilution internal standardization has been established. Plasma samples were subjected to protein precipitation prior to their injection into a column for subsequent separation (Thermo Accucore aQ C 18 , 50 × 2.1 mm, 2.6 μm). Positive electrospray ionization (ESI) mode with selected reaction monitoring (SRM) was used for analytes determination. Results Busulfan and cyclophosphamide could be measured within 3 min, with the calibration ranges of 80–4000 ng/mL for busulfan and 25–2000 ng/mL for cyclophosphamide. The validated method showed good sensitivity and linearity. Accuracies and precisions were less than 15 %. The results of stability showed that busulfan and cyclophosphamide were stable in the plasma under room temperature for 16 h, 4 °C for 24 h, −80 °C for 2 weeks, and after three freeze-thaw processes. Conclusion The bioassay was simple, sensitive and successfully implemented in the realm of TDM for Bu-Cy, ultimately leading to improved dosing precision.
研究领域:
药理学
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临床化学
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肿瘤学
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分析化学
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血液学
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DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL THERMODYNAMICS
·
2020
·
IF 2.888
Jiao Sha,Zidan Cao,Zibo Huang,Yi Gong,Yameng Wan,Renren Sun,Haixia He,Gaoliang Jiang,Yu Li,Tao Li,Baozeng Ren
The equilibrium solubility and thermodynamic properties of busulfan in fifteen organic single solvents were reported. Solubility determinations were performed through the laser monitoring method at T = (278.15–323.15) K (except DMSO at 298.15–323.15 K) and p = 101.3 kPa. It can be found that the mole fraction solubility of busulfan increases apparently with the augmented experimental temperature. The solubility of busulfan in single solvents exhibits the following order from maximum to minimal at 303.15 K: NMP (4.870e−2) > DMSO (4.591e−2) > DMF (3.966e−2) > methyl acetate (4.502e−3) > 2-methoxyethanol (3.105e−3) > ethyl acetate (2.090e−3) > n-propyl acetate (1.367e−3) > 2-ethoxyethanol (1.280e−3) > n-butyl acetate (9.618e−4) > 2-propoxyethanol (6.930e−4) > 2-butoxyethanol (5.219 e−4) > methanol (3.787e−4) > ethanol (1.423e−4) > n-propanol (6.680e−5) > n-butanol (6.350e−5). The maximum value in busulfan solubility profile is related to DMSO at 323.15 K ( x 1 = 1.035 e−1) and the minimum one is obtained for n-butanol (6.800e−6, T = 278.15 K). The results of using KAT-LSER model to study the solvent effect of busulfan solubility in fifteen single solvents show that solute-solvent interactions are principally attributed to the dipolarity/polarizability interaction and the hydrogen bonding basicity. And then, the determined solubility values of busulfan have been fitted to five widely used thermodynamic models, namely, λh, modified Apleblat, NRTL, NRTL-SAC and UNIQUAC models. The calculated results via the five models were all consistent with the solubility values, indicating that all models could provide high fitting accuracy. Moreover, according to the results of apparent thermodynamic properties calculated by Van’t Hoff equation, it can be stated that the dissolution process of busulfan in all selected solvents is recorded as an endothermic, non-spontaneous process driven by entropy.
研究领域:
化学工程
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物理化学
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药学
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热力学
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产品关联
DOI
高影响因子
PeerJ
·
2024
·
IF 2.3
Jin Dong,Taowen Ye,Yanli Dong,Jie Hui,Xiaorong Wang
Background Oligospermia is one of the most common reasons for male infertility which is troubling numerous couples of child-bearing age. This investigation scrutinizes the implications and mechanistic underpinnings of ursolic acid’s effect on busulfan-induced oligospermia in mouse models. Methods A singular intraperitoneal injection of busulfan at a dosage of 30 mg/kg induced oligospermia. Two weeks subsequent to this induction, mice were subjected to various dosages of ursolic acid (10, 30, and 50 mg/kg body weight, respectively) on a daily basis for four consecutive weeks. Following this treatment period, a meticulous analysis of epididymal sperm parameters, encompassing concentration and motility, was conducted using a computer-assisted sperm analysis system. The histopathology of the mice testes was performed utilizing hematoxylin and eosin staining, and the cytoskeleton regeneration of the testicular tissues was analyzed via immunofluorescent staining. Serum hormone levels, including testosterone, luteinizing hormone, and follicle-stimulating hormone, as well as reactive oxygen species levels (inclusive of reactive oxygen species and malondialdehyde), were gauged employing specific enzyme-linked immunosorbent assay kits. Differentially expressed genes of testicular mRNA between the oligospermia-induced group and the various ursolic acid treatment groups were identified through RNA sequencing analysis. Results The results revealed that a dosage of 50 mg/kg ursolic acid treatment could increase the concentration of epididymal sperm in oligospermia mice, promote the recovery of testicular morphology, regulate hormone levels and ameliorate oxidative damage. The mechanism research results indicated that ursolic acid increased the expression level of genes related to motor proteins in oligospermia mice.
研究领域:
生殖生物学
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药理学
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分子生物学
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组织病理学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2023
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IF 7.5
Hai-Tao Li,Kun Zhong,Yun-Fei Xia,Jian Song,Xiao-Qing Chen,Wei Zhao,Xu-Hui Zeng,Tian-Xing Chen
Male infertility is a global concern, with a noticeable increase in the decline of spermatogenesis and sperm quality. However, there are limited clinically effective treatments available. This study aimed to investigate the potential effectiveness of puerarin in treating male infertility, which leads to gonadal changes. The results obtained from various analyses such as CASA, immunofluorescence, DIFF-Quick, hematoxylin and eosin (H&E), and periodic acid-Schiff (PAS) staining demonstrated that puerarin supplementation significantly alleviated the busulfan-induced reduction in spermatogenesis and sperm quality in both young and adult mice. Furthermore, puerarin exhibited a marked improvement in the damage caused by busulfan to the architecture of seminiferous tubules, causal epididymis, blood-testicular barrier (BTB), as well as spermatogonia and Sertoli cells. Similarly, puerarin significantly reduced the levels of total antioxidant capacity (T-AOC), malondialdehyde (MDA), and caspase-3 in the testes of busulfan-induced mice, as determined by microplate reader analysis. Additionally, RNA-seq data, RT-qPCR, and western blotting revealed that puerarin restored the abnormal gene expressions induced by busulfan to nearly healthy levels. Notably, puerarin significantly reversed the impact of busulfan on the expression of marker genes involved in spermatogenesis and oxidative stress. Moreover, puerarin suppressed the phosphorylation of p38, ERK1/2, and JNK in the testes, as observed through testicular analysis. Consequently, this study concludes that puerarin may serve as a potential alternative for treating busulfan-induced damage to male fertility by inactivating the testicular MAPK pathways. These findings may pave the way for the use of puerarin in addressing chemotherapy- or other factors-induced male infertility in humans.
研究领域:
生殖生物学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2020
·
IF 4.099
Xi Zhao,Zhenhua Liu,Jie Gao,Hu Li,Xiaorong Wang,Yinchuan Li,Fei Sun
Busulfan is commonly used for cancer chemotherapy, nevertheless it cause male infertility via damaging the germ cells. Therefore, the underlying mechanism should be explored. In the present study, we demonstrated for the first time that ferroptosis was involved in busulfan-induced oligospermia in mice. Mice were given testicular injection of busulfan on both sides at the dose of 4 mg/kg body weight to establish the model of oligospermia. Four weeks later, the results showed that busulfan-treated mice exhibited decreased sperm concentration and motility, along with features of typical ferroptosis in testis, such as increased malondialdehyde (MDA) content and prostaglandin-endoperoxide synthase (PTGS2) mRNA expression, and decreased NADPH content. Inhibition of ferroptosis by ferrostatin-1 (Fer-1) or deferoxamine (DFO) partially alleviated busulfan-induced oligospermia in mice. Additionally, we also revealed that busulfan treatment induced spermatogenic cells ferroptosis by down-regulating nuclear factor-E2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4) expressions, and decreasing iron efflux through reduction of ferroportin 1 (FPN1) expression. Fer-1 or DFO obviously reversed busulfan-induced ferroptosis by increasing Nrf2, GPX4 and FPN1 expressions. Furthermore, after activation of Nrf2 by sulforaphane, sperm concentration and motility in busulfan-treated mice increased, accompanied by enhanced expressions of GPX4 and FPN1. These findings imply that busulfan-induced ferroptosis might be mediated via inhibition of Nrf2-GPX4 (FPN1) signaling pathway, and highlight that targeting ferroptosis serves as a potential strategy for prevention of busulfan-induced damage and male infertility.
研究领域:
药理学
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生殖生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Leilei Gong,Jinli Hou,Hongjun Yang,Xueyan Zhang,Jingxia Zhao,Lan Wang,Xiaojie Yin,Xin Feng,Chenghong Yin
Ethnopharmacological relevance Classical prescriptions are not only a primary method of clinical treatment in traditional Chinese medicine (TCM) but also represent breakthroughs in the inheritance and development of this field. Kuntai capsule (KTC), a formulation based on a classical prescription, comprises six TCMs: Rehmanniae Radix Praeparata, Coptidis Rhizoma , Paeoniae Radix Alba , Scutellariae Radix , Asini Corii Colla, and Poria . This formulation possesses various beneficial effects, such as nourishing yin and blood, clearing heat and purging fire, and calming the nerves and relieving annoyance. The investigation of the efficacy and mechanism of KTC in regulating anti-aging factors in the treatment of premature ovarian insufficiency (POI) is not only a prominent topic in classical prescription research but also a crucial issue in the treatment of female reproductive aging using TCM. Aim of the study To evaluate the therapeutic effect of KTC on POI and its underlying mechanism. Materials and methods Healthy and specific pathogen-free (SPF) female Kunming mice aged 6–8 weeks were selected. After acclimatization, the mice were randomly divided into a control, model, and high, middle, and low dose groups of KTC (1.6, 0.8, and 0.4 mg/kg, respectively). Except for the control group, the animals in the other groups were administered a single intraperitoneal injection of 120 mg/kg cyclophosphamide and 30 mg/kg Busulfan to induce the model of POI. After modeling, the mice were treated with the corresponding drugs for 7 days. Serum and ovarian tissues were collected, and the levels of serum follicle-stimulating hormone (FSH), estradiol (E2), and superoxide dismutase 2 (SOD2) were determined using enzyme-linked immunosorbent assay (ELISA). The chemical composition of KTC was characterized and analyzed using ultra-high-pressure liquid chromatography-linear ion trap-Orbitrap tandem mass spectrometry. A “drug-component-target-pathway-disease” network was constructed using network pharmacology research methods to identify the key active components of KTC in treating POI and to elucidate its potential mechanism. The protein expression of the FOXO3/SIRT5 pathway was detected by western blotting . Results Compared to the model group, the high-dose group of KTC showed a significant increase in ovarian index, significant increase in levels of E2 and SOD2, and a significant decrease in FSH levels. Through systematic analysis of the chemical constituents of KTC, 69 compounds were identified, including 7 organic acids, 14 alkaloids, 28 flavonoids , 15 terpenoids , 2 lignans , 2 phenylpropanoids, and 1 sugar. Based on network pharmacology research methods, it was determined that KTC exerts its therapeutic effect on POI through multiple components (paeoniflorin and malic acid), multiple targets (FOXO3 and SIRT5), and multiple pathways (prolactin signaling pathway, longevity regulating pathway, and metabolic pathways). The accuracy of the network pharmacology prediction was further validated by detecting the protein expression of SIRT5 and FOXO3a, which showed a significant increase in the middle and high-dose groups of KTC compared to the model group. Conclusions KTC may effectively treat POI through a multi-component, multi-target, multi-pathway approach, providing an experimental basis for using KTC based on classical prescriptions in the treatment of POI.
研究领域:
药理学
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中医妇科
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信号传导
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分析化学
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整合药理学
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产品关联
DOI
PubMed
高影响因子
Journal of the American Chemical Society
·
2026
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IF 16.6
Xiaofei Xin,Yifu Lyu,Huanyu Qin,Jinyu Dai,Di Wu,Yu Ding,Qiang Tian,Chao Qin,Na Li,Lifang Yin
The rational design of nonlamellar, multicompartment lipid nanoparticles (LNPs) offers a promising strategy for advancing nucleic acid delivery and immunotherapy. In this study, imidazole-based LNPs (A3-DM/DL-LNPs) with a mesoscopically disordered internal structure resembling the sponge phase were developed, enabling efficient codelivery of mRNA and STAT3-targeting siRNA (siSTAT3). Small-angle scattering analysis revealed a unique quasi-periodic arrangement in A3-DM/DL-LNPs, characterized by broader interdomain spacing and higher membrane heterogeneity compared to benchmark ALC-0315-LNPs, suggesting enhanced endocytosis efficiency and more favorable RNA encapsulation. The “M-shaped” polar headgroup, formed by a piperazine ring flanked by two imidazole moieties, promoted membrane interaction, cellular uptake, and transfection efficiency. In contrast, alternative LNPs with linear polar head structures (A3-SS/SM/SL-LNPs and A4-SS/SM/SL-LNPs) showed inferior delivery performance. Raman spectroscopy revealed that lipid spatial localization correlated with RNA expression in the spleen and lymph nodes, highlighting the importance of LNP structure in immune activation and targeting specific immune organs. Functionally, A3-DM/DL-LNPs restored dendritic cell (DC) antigen presentation, alleviated endoplasmic reticulum (ER) stress, and reversed T cell exhaustion in acute myeloid leukemia (AML), triggering strong immune responses and enhancing natural killer (NK) cell and T cell-mediated antileukemic activity, thereby improving therapeutic outcomes.
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2020
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IF 5.339
Zhixia Yao,Hanmeng Liu,Yaosheng Liu,Yongxing Diao,Guangxing Hu,Qifang Zhang,Zhuang Li
A novel fluorometric strategy is proposed for detecting curcumin by polyvinyl pyrrolidone-templated Cu NCs (PVP–Cu NCs) as a fluorescent probe which exhibits excitation/emission peaks at 380/510 nm. The fluorescent excitation and emission spectra of PVP-Cu NCs have a striking overlap with the UV–vis spectrum of curcumin, and the fluorescence lifetime of PVP-Cu NCs decreases after the addition of curcumin. Curcumin leads to fluorescence quenching based on fluorescence resonance energy transfer . This method allows for the determination of curcumin in the range of 0.1–10 μg mL −1 and the detection limit is 21 ng mL −1 . Furthermore, this method displays good selectivity and is successfully applied for real sample analysis.
研究领域:
分析化学
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生物化学
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产品关联
DOI
PubMed
高影响因子
INORGANIC CHEMISTRY
·
2015
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IF 4.762
De-Yun Ma,Zhi Li,Jun-Xia Xiao,Rong Deng,Pei-Feng Lin,Rui-Qun Chen,Yun-Qiu Liang,Hai-Fu Guo,Bei Liu,Jian-Qiang Liu
By using a strategy of introducing hydrophobic groups to the linkers, a hydrostable MOF was constructed based on 5-nitroisophthalate and 2,2′-dimethyl-4,4′-bipyridine coligands, revealing a 3D dia topology structure with a 1D channel parallel to the c axis. TGA, PXRD, and water vapor sorption results show high thermal and water stability for the framework. The framework is very porous and possesses not only high busulfan payloads with an encapsulation efficiency up to 21.5% (17.2 wt %) but also very high CO2 selective capture compared with that of other small gases (i.e., CH4, N2, O2, CO, and H2) at 298 K based on molecular simulations due to the pore surface being populated by methyl and nitryl groups. Furthermore, in vitro MTT assays were conducted on four different cells lines with increasing concentrations of the framework, and the results showed that the framework was nontoxic (cell viability >80%) in spite of the concentrations up to 500 μg/mL.
研究领域:
材料科学
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生物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
Reproductive Sciences
·
2020
·Vol. 27
·期 7
·1502-1512
·
IF 2.616
Feng Xiushan,Ling Li,Zhang Wenqian,Liu Xiaohan,Wang Yaping,Luo Yanjing,Xiong Zhengai
Human amnion–derived mesenchymal stem cell (hAD-MSC) transplantation can repair ovarian injury and improve ovarian function in rats with chemotherapy-induced primary ovarian insufficiency (POI). However, ensuring that stem cells home to the ovary to improve their effects on ovarian injury is challenging. This research aimed to directly inject ovarian tissue with hAD-MSCs and improve the homing of stem cells to the ovary. The animals were divided into POI, hAD-MSC (tail vein) treatment, hAD-MSC (in situ) treatment, and control groups. POI rat models were established by intraperitoneal injection of cyclophosphamide (CTX) and busulfan (BUS). The hAD-MSCs isolated from the amnion were injected into the tail vein or ovary of POI rats. The estrous cycle, serum sex hormone levels, follicle counts, ovarian pathological changes, and proteome of the ovaries were evaluated. hAD-MSCs were successfully isolated and cultured from the amnion. Both hAD-MSC (tail vein) and hAD-MSC (in situ) transplantation increased body weight, improved the AMH levels and follicle numbers, and reduced reproductive organ injuries in POI rats. Transplantation of hAD-MSCs (in situ) upregulated 24 proteins and downregulated 4 proteins. Both hAD-MSC (tail vein) and hAD-MSC (in situ) transplantations can repair ovarian injury and improve ovarian function in rats with chemotherapy-induced POI. The paracrine proteome of hAD-MSCs in the ovarian microenvironment can protect against chemotherapy-induced damage by reducing apoptosis and promoting angiogenesis, cell proliferation, and gene expression.
研究领域:
干细胞生物学
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生殖医学
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肿瘤学
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蛋白质组学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Yi Xiao,Haomin Yi,Jingzhi Zhu,Suhua Chen,Guofang Wang,Yilong Liao,Yuanyuan Lei,Liyin Chen,Xingcai Zhang,Fangfu Ye
Toxicity assessment is a major problem in pharmaceutical candidates and industry chemicals development. However, due to the lack of practical analytical methods for DNA adduct analysis, the safety evaluation of drug and industry chemicals was severely limited. Here, we develop a DNAzyme-based method to detect DNA adduct damage for toxicity assessment of drugs and chemicals. Among 18 structural variants of G4 DNAzyme, EA2 DNAzyme exhibits an obvious DNA damaging effect of styrene oxide (SO) due to its unstable structure. The covalent binding of SO to DNAzyme disrupts the Hoogsteen hydrogen bonding sites of G-plane guanines and affects the formation of the G4 quadruplex. DNA damage chemicals reduce the peroxidase activity of the G4 DNAzyme to monitor the DNA adduct damage by disrupting the structural integrity of the G4 DNAzyme. Our method for genotoxic assessment of pharmaceutical candidates and industrial chemicals can elucidate the complex chemical pathways leading to toxicity, predict toxic effects of chemicals, and evaluate possible risks to human health.
研究领域:
分子生物学
·
毒理学
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药学
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化学工程
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产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2022
·
IF 4.831
Yi Zhang,Qingbo Deng,Chang Tang,Minglu Zhang,Zilong Huang,Zhifeng Cai
Development of excellent sensors to determine trace concentrations of rifampicin is of intense importance for medicine analysis and human health. Herein, a facile and green fluorescent probe was established for the determination of rifampicin by using folic acid protected copper nanoclusters (FA-Cu NCs). Many characterization methods were applied for the analysis of the as-prepared FA-Cu NCs including UV–visible absorption spectra, fluorescence spectra, Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscope (TEM), fluorescence lifetime and X-ray photoelectron spectroscopy (XPS). The TEM image suggested that the as-prepared FA-Cu NCs were highly dispersed. The as-synthesized FA-Cu NCs emerged blue fluorescence under UV light and demonstrated maximum emission wavelength at 446 nm under the maximum excitation wavelength of 358 nm. After the addition of rifampicin, the FL intensities of FA-Cu NCs were uncommonly quenched. The related experimental data intimated that the quenching mechanisms were assumed to the inner filter effect (IFE) and static quenching. The as-proposed probe platform displayed an obvious linear relationship with rifampicin concentrations varying from 0.5 to 100 µM, and the corresponding detection limit (LOD) was 0.073 µM (S/N = 3). Finally, the as-established detection platform was successfully employed to analyze trace concentrations of rifampicin in real samples.
研究领域:
分析化学
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医学检测
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）