ACS Omega
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2025
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IF 4.3
Liu-Yan Liang,Ting-Yin Lu,Long-Gen Zhong,Wen-Hui Su,Zi-Qi Ren,Meng-Ting Tao,Jian Sun,Xiao-Ping Liao,Dong-Hao Zhao,Yu-Feng Zhou
Shikimic acid, a widely known hydroaromatic compound abundantly found in Illicium verum (commonly known as Chinese star anise), serves as a key intermediate in the synthesis of neuraminidase inhibitors such as oseltamivir. However, its pharmacokinetic (PK) properties and long-term safety profile remain inadequately characterized. This study systematically evaluated its PK behavior following both oral and intravenous administrations, along with its acute toxicity and 28-day subchronic oral toxicity in mice. PK analysis for shikimic acid demonstrated linear and dose-proportional behavior within the intravenous dose range of 4–16 mg/kg. Shikimic acid was rapidly eliminated from plasma, with a short terminal half-life (T1/2) of 0.76–0.85 h. Despite rapid absorption (Tmax, 0.95–1.25 h) following oral administration, a low bioavailability ranging from 11.09 to 20.44% was observed in mice. Acute toxicity testing showed no mortality at oral doses of up to 10,000 mg/kg. In the 28-day subchronic oral toxicity study, mice fed diets containing high (50 g/kg), medium (16.67 g/kg), or low (5.56 g/kg) doses of shikimic acid exhibited no mortality. Hematological assessments revealed slight elevations in neutrophil counts, eosinophil counts, and hematocrit levels in the high-dose group compared to controls. Notably, a significant reduction in triglyceride levels was observed in the high-dose group, suggesting potential hypolipidemic effects for shikimic acid. Collectively, these findings provide foundational data on the PKs, safety, and tolerability of shikimic acid, supporting its further development for potential therapeutic applications.
研究领域:
药理学
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毒理学
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药物代谢
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生物药剂学
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药物化学
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产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
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2022
·Vol. 20
·期 1
·1-14
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IF 8.44
Mu Shuwen,Lin Yinghong,Xu Yongjun,Wei Xianqing,Zeng Zihuan,Lin Kunzhe,Zhu Linghua,Liu Qinghong,Qi Xingfeng,Wei Liangfeng,Liang Shengxiang,Wang Shousen
Background Cerebral venous sinus thrombosis (CVST) is a rare neurovascular disorder with highly variable manifestations and clinical courses. Animal models properly matched to the clinical form of CVST are necessary for elucidating the pathophysiology of the disease. In this study, we aimed to establish a rat model that accurately recapitulates the clinical features of CVST in human patients. Methods This study consisted of a clinical analysis and animal experiments. Clinical data for two centres obtained between January 2016 and May 2021 were collected and analysed retrospectively. In addition, a Sprague–Dawley rat model of CVST was established by inserting a water-swellable rubber device into the superior sagittal sinus, following which imaging, histological, haematological, and behavioural tests were used to investigate pathophysiological changes. Principal component analysis and hierarchical clustering heatmaps were used to evaluate the similarity between the animal models and human patients. Results The imaging results revealed the possibility of vasogenic oedema in animal models. Haematological analysis indicated an inflammatory and hypercoagulable state. These findings were mostly matched with the retrospective clinical data. Pathological and serological tests further revealed brain parenchymal damage related to CVST in animal models. Conclusions We successfully established a stable and reproducible rat model of CVST. The high similarity between clinical patients and animal models was verified via cluster analysis. This model may be useful for the study of CVST pathophysiology and potential therapies.
研究领域:
神经病学
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实验医学
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病理学
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生物统计学
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DOI
PubMed
高影响因子
BIOMATERIALS
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2013
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IF 7.604
Yan Zhang,Yejun Zhang,Guosong Hong,Wei He,Kun Zhou,Kai Yang,Feng Li,Guangcun Chen,Zhuang Liu,Hongjie Dai,Qiangbin Wang
Ag 2 S quantum dots (QDs) have been demonstrated as a promising near-infrared II (NIR-II, 1.0–1.4 μm) emitting nanoprobe for in vivo imaging and detection. In this work, we carefully study the long-term in vivo biodistribution of Ag 2 S QDs functionalized with polyethylene glycol (PEG) and systematically examine the potential toxicity of Ag 2 S QDs over time. Our results show that PEGylated-Ag 2 S QDs are mainly accumulated in the reticuloendothelial system (RES) including liver and spleen after intravenous administration and can be gradually cleared, mostly by fecal excretion. PEGylated-Ag 2 S QDs do not cause appreciable toxicity at our tested doses (15 and 30 mg/kg) to the treated mice over a period of 2 months as evidenced by blood biochemistry , hematological analysis and histological examinations. Our work lays a solid foundation for further biomedical applications of Ag 2 S QDs as an important in vivo imaging agent in the NIR-II region.
研究领域:
生物医学工程
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药理学
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毒理学
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纳米技术
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成像科学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Xueqing He,Songyi Lin,Lei Chen,Yihan Huang,Jinhui Hu,Na Sun
Iron fortification with food supplements remains the primary dietary strategy for improving iron deficiency anemia (IDA). This study used Antarctic krill protein for fibrillar design to form an Antarctic krill protein amyloid fibril (AKAF). The results indicated that peptides generated by proteolysis were a prerequisite for fibril assembly, forming elongated fibril structures and cross-linking upon heating. During this process, hydrogen bonds were rearranged, forming ordered β-sheet conformations (49.36 ± 0.21%); π–π stacking interactions among aromatic residues contributed to fibril formation. Further studies showed that AKAF effectively maintained iron in a bioavailable state and exhibited a high binding capacity (60.67 ± 0.69%). Moreover, the AKAF-iron complex markedly ameliorated hematological abnormalities in IDA mice, enhanced iron storage in the liver and spleen, and positively influenced the expression of iron homeostasis genes. This complex was also effective in alleviating gastric inflammatory responses induced by IDA. Overall, AKAF holds promise as an efficient iron delivery carrier.
研究领域:
营养学
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生物化学
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食品科学
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分子生物学
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医学研究
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产品关联
DOI
PubMed
高影响因子
Nanoscale
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2024
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IF 5.8
Xinru Kong,Yanxi Yang,Xueli Ren,Yandai Lin,Yu Shi,Zhe Liu
The concept of combining external medical stimuli with internal functional biomaterials to serve cancer-oriented treatments is emergingly developed. Optical and acoustical activations have shown special promises as non-invasive regulation modalities in cancer treatment and intervention. It is always challenging to leverage their contributions between optical and acoustical stimuli and find the appropriate biomaterials to optimally match them. Herein, a type of hybrid nanomicelles (ICG@PEP@HA) containing ICG as photo/sonosensitizers, an amphiphilic peptide for membrane penetration and hyaluronic acid for cluster determinant 44 (CD44) targeting were fabricated. Triggered by external stimuli of laser and US irradiations, their photo/sonothermal performances, in vitro reactive oxygen species (ROS) production capabilities and tumor-targeting efficiency have been systematically evaluated. It was interestingly found that the external stimulus of laser induced more quantity of ROS which resulted in a significant cell apoptosis and tumor growth inhibition in the presence of ICG@PEP@HA. The individual analysis and corresponding rationales have been investigated. In the meanwhile, these hybrid nanomicelles were administered into the MDA-MB-231 tumor-bearing nude mice for PDT and SDT therapies and their biocompatibility assessment, and a PDT prevailing efficacy and reliable bio-safety have been evidenced based on the hematological analysis and histochemical stainings. In summary, this study has validated a novel pathway to utilize these hybrid nanomicelles for laser/US-triggered localized tumor treatments, and the treatment efficiency may be leveraged by different external stimuli sources. It is also expected to give birth to full accessibility to clinical translations for human cancer treatments by means of as-reported laser/US-nanomicelles combination strategy.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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药学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
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2024
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IF 4.4
Shuang-Shuang Zhang,Jia-Hui Yu,Si-Si Jiang,Lun Wang,Jiong Chen,Jiao Long,Shuang-Xi Gu,Hui Li
P-glycoprotein (P-gp) overexpressed mutidrug resistance (MDR) is currently a key factor limiting the effectiveness of breast cancer chemotherapy. Systemic administration based on P-gp-associated mechanism leads to severe toxic side effects. Here, we designed a T7 peptide-modified mixed liposome (T7-MLP@DTX/SchB) that, by active targeting co-delivering chemotherapeutic agents and P-gp inhibitors, harnessed synergistic effects to improve the treatment of MDR breast cancer. This study established drug-resistant cell models and animal models. Subsequently, comprehensive evaluations involving cell uptake, cell apoptosis, cellular toxicity assays, in vivo tumor-targeting capability, and anti-tumor activity assays were conducted to assess the drug resistance reversal effects of T7-MLP@DTX/SchB. Additionally, a systematic assessment of the biosafety profile of T7-MLP@DTX/SchB was executed, including blood profiles, biochemical markers, and histopathological examination. It was found that this co-delivery strategy successfully exerted the synergistic effects, since there was a significant tumor growth inhibitory effect on multidrug-resistant breast cancer. Targeted modification with T7 peptide enhanced the therapeutic efficacy remarkably, while vastly ameliorating the biocompatibility compared to free drugs. The intriguing results supported the promising potential use of T7-MLP@DTX/SchB in overcoming MDR breast cancer treatment.
研究领域:
药学
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肿瘤学
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生物技术
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纳米医学
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
Frontiers in Medicine
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2025
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IF 3
Xiaohui Gao,Hui Zeng,Fei Sun,Xiaoyan Zhao,Haibing Wu,Minchao Yan,Yuan Li,Qinyan Fu,Gang Zhang
Purpose: This study aimed to evaluate the underlying mechanisms of decitabine (DAC) in inhibiting acute T-acute lymphoblastic leukemia (T-ALL) cell proliferation and promoting apoptosis.Methods: Human T-ALL cells (CCRF-CEM) were treated with varying concentrations of DAC, and cell proliferation was assessed using a CCK-8 assay. Flow cytometry was used to detect apoptosis and cell cycle alterations. The expression levels of apoptosis-related genes, including PI3K and miR-92b-3p, were quantified using real-time PCR (RT-PCR). Western blotting was used to analyze the expression of apoptotic proteins. Furthermore, we evaluated the in vivo antileukemic activity of DAC using a nude mouse xenograft model, monitored the body weight and tumor volume of mice to calculate inhibition rates, and examined tumor morphological changes in histological sections.Results: DAC significantly inhibited the proliferation of CCRF-CEM cells, accelerated apoptosis, and effectively downregulated the expression of PI3K, AKT, 4EBP1, and mTOR while concurrently upregulating PTEN protein expression. Its regulatory efficacy was markedly enhanced by increasing the dosage. Animal experimental results indicated that both DAC and doxorubicin substantially decreased tumor length, width, volume, and mass; however, DAC demonstrated significantly superior efficacy in inhibiting tumor growth compared to doxorubicin.Conclusion: By selectively targeting the regulation of PTEN and 4EBP1, along with their associated downstream signaling pathways, DAC effectively modulated cellular proliferation, facilitated apoptotic processes, and restrained tumor growth, providing a robust theoretical foundation for clinical treatment strategies in T-ALL.
研究领域:
血液学
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肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
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2025
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IF 4.6
Jin Zhou,Pinpin Sui,Jianxin Zhao,Xiurong Cheng,Tao Yu,Shiwei Cui,Xiangrong Song,Caihong Xing
Patients with benzene-induced leukemia undergo a continuous transformation from myelosuppression to malignant proliferation. However, the underlying mechanisms in this process remain unknown. Our previous studies have shown that the pathways involved in self-renewal capacity of bone marrow (BM) cells in Mll-Af9 mice exposed to benzene for life are significantly activated after severe blood toxicity. In order to investigate the hematotoxicity effects of benzene on the self-renewal capacity of HSCs, Mll-Af9 chimeric mice were exposed to benzene and hematological parameters were dynamically monitored after benzene exposure. Transcriptomic analysis were used to analyze different time points during benzene exposure and after competitive bone marrow transplantation (BMT). Results showed that despite severe hematotoxicity in mice, but the chimerism rate of Mll-Af9 cells in peripheral blood (PB) cells was significantly increased after 10 weeks benzene exposure ( P < 0.001). After competitive BMT, the chimerism rate of Mll-Af9 cells from 10 weeks benzene-exposed mice was gradually increased and significantly surpassed that of the control at 26 weeks of bone marrow reconstruction (benzene group 86 % VS control group 78 %, P = 0.03). Transcriptome analysis revealed that the expression levels of self-renewal related genes, such as Hox genes ( Hoxb4 , Hoxa7 , Hoxa10 ), Mecom and Ms4a in BM cells of 10 weeks benzene-exposed mice were relatively higher compared to those in the control group, but no significant difference were observed. Interestingly, Hoxa7 , Hoxa10 and Mecom were significantly up-regulated at 26 weeks after bone marrow transplantation. In conclusion, our study suggests that abnormal expression of self-renewal-related genes may be potential early biomarkers for benzene-induced hematotoxicity. This hematotoxicity may contribute to the acquisition of evolutionary advantages by leukemic precursor cells and accelerate malignant transformation.
研究领域:
血液学
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毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2025
·
IF 5.1
Kaiji Li,Jinchao Wang,Yalong Gao,Xin Chen,Ruilong Peng,Lei Li,Cong Wang,Tuo Li,Shu Zhang,Guili Yang,Jianning Zhang
Aims Traumatic brain injury-induced coagulopathy (TBI-IC) frequently occurs after TBI, exacerbating the severity of TBI and affecting patient prognosis. Benzbromarone (BBR) is commonly used to treat hyperuricemia; however, its protective effects against TBI-IC remain unknown. Therefore, we explored whether BBR could improve TBI. Materials and methods C57BL/6 wild-type mice were subjected to fluid percussion injury to mimic TBI, and BBR was administered intraperitoneally 30 min after TBI. Magnetic resonance imaging (MRI) and Evans blue dye extravasation were used to assess the prognosis, tail bleeding time, ELISA, and coagulation tests assess coagulation function. We further explored the potential mechanism by which BBR alleviates hypercoagulation after TBI using flow cytometry. Key findings The intraperitoneally injected BBR group showed improved survival and neurological severity scores compared to the TBI group. Subsequently, we found that hypercoagulability developed 3 h after TBI and that the administration of BBR improved this hypercoagulability. BBR also reduced the degree of platelet phosphatidylserine (PS) exposure after TBI, platelet activation, and Ca2+ overload, in addition to inhibition of scramblase activity in procoagulant platelets. Significance Our findings indicate that BBR reduces PS externalization by inhibiting TMEM16F expression, thereby improving blood hypercoagulability after TBI.
研究领域:
神经科学
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药理学
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血液学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
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2025
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IF 14.1
Tong Zhang,Tian Liang,Qichao Pan,Shouyan Zhang,Shuhua Zhang,Zhi Geng,Bo Zhu
Blood-contacting catheters are highly susceptible to thrombus formation, making heparin coating essential for reducing clinical complications. However, the limitations of heparin coatings have spurred significant efforts to develop alternative strategies. This study demonstrates a cost-efficient, mechanically viable, and universal zwitterion coating approach for long and complex catheters with near-zero fouling, super anticoagulation, and selective biocapturing. Leveraging the synergistic action of side groups, a wet-adhesive initiator-bearing polymer rapidly assembles on catheter surfaces in aqueous environments, facilitating the grafting of superhydrophilic and zwitterionic polymers onto catheter inner walls. This strategy demonstrates broad adaptability, successfully applying to ten substrates and showing exceptional versatility in modifying catheters and joints of various shapes and sizes. These coatings exhibit near-zero protein fouling across a broad pH range, and superior resistance to blood cells and bacteria. Furthermore, they maintain excellent stability under simulated bloodstream without compromising anticoagulant performance. Beyond antifouling properties, this method enables the construction of highly selective bio-interaction networks on catheter inner walls, allowing precise capture of circulating tumor cells from blood. This zwitterion coating technique, with its rapid modification, robust anticoagulant properties, and customizable bio-functionality, provides an attractive solution for, beyond catheters, a wide range of medical devices that must perform in challenging biological environments.
研究领域:
生物医学工程
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材料科学
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血液学
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产品关联
DOI
PubMed
高影响因子
Indian Journal of Hematology and Blood Transfusion
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2024
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IF 0.7
Liu Xiaoyu,Yang Lin,Guan Kunping,Chen Zhen,Yang Hua
Purpose This study aims to investigate the increased toxicity of Cytarabine (Ara-c) by knockdown of chromosome segregation 1-like (CSE1L) in acute myeloid leukemia(AML) cells(Kasumi-1, U937, and THP-1 cells) and to explore its possible mechanisms. Methods Target gene silencing was achieved using the shRNA-mediated lentivirus method. Apoptosis was identified using the Annexin V PE/7-AAD double-staining assay. Cell viability was assessed with the Cell Counting Kit-8 (CCK-8) assay. Protein expression was detected by Western blotting. Results In vitro, knocking down CSE1L promoted caspase-3 and caspase-9 proteins expression and induced apoptosis in AML cells. Knockdown of CSE1L enhanced AML cells' sensitivity to Ara-c. knockdown of CSE1L reduced the expression levels of p-JKA2 and p-STAT3 proteins, while no significant difference was observed in the expression levels of total JAK2 and STAT3 proteins. Furthermore, JAK2 overexpression reversed the increase in Ara-c toxicity to AML cells caused by CSE1L knockdown. Conclusion In conclusion, our study reveals that CSE1L is a potential therapeutic target for overcoming Ara-c resistance in AML cells. Thus, we have gained new insights into the oncogenic process of CSE1L in AML cells and raised the prospect of knockdown of CSE1L in AML in combination with cytarabine-targeted therapy.
研究领域:
肿瘤学
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血液学
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分子生物学
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细胞生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
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2024
·Vol. 26
·期 11
·1-14
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IF 2.1
Ma Yuying,Wu Hai,Jia Min,Zhang Zhijun,Wang Jingwei,Yue Zhenggang,Wu Hong,Yang Tiehong
This investigation is aimed to develop a novel iron supplement, iron oxide nanoparticles modified with Angelica sinensis polysaccharide (IONPs-ASP), for the treatment of iron deficiency anemia (IDA). IONPs-ASP was synthesized using the co-precipitation method and characterized for their structural features, physicochemical properties, and biocompatibility by TEM, SEM, FTIR, etc. The therapeutic effects of IONPs-ASP were assessed in a rat IDA model. IONPs-ASP was administered intravenously, and blood parameters were monitored. In addition, the preliminary safety of IONPs-ASP was evaluated by organ coefficients and histopathological staining. IONPs-ASP was successfully constructed, with a small particle size, core–shell structure, hydrophilicity, and good biocompatibility. Compared to unmodified IONPs, IONPs-ASP showed better stability and dispersion. In the IDA rat model, IONPs-ASP exhibited superior therapeutic efficacy than that of ASP or IONPs monotherapy. Furthermore, no abnormalities were observed in the organ coefficients and tissue section. IONPs-ASP not only has a superior therapeutic effect on IDA but also has the effect of the ASP on supplementing blood. Hence, it may be used as a new iron supplementing agent with double therapeutic efficacy on blood supplementation for the treatment of IDA. Graphical Abstract In this study, we constructed Angelica sinensis polysaccharide (ASP)–modified iron oxide nanoparticles (IONPs) and demonstrated the therapeutic effects of IONPs-ASP on iron deficiency anemia (IDA), which was associated with IONPs supplementation and APS-stimulated hematopoietic cell generation.
研究领域:
纳米技术
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药理学
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生物医学工程
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血液学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）