Biology-Basel
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2023
·Vol. 12
·期 9
·1214
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IF 4.2
Ferry Saputra,Yu-Heng Lai,Marri Jmelou M. Roldan,Honeymae C. Alos,Charlaine A. Aventurado,Ross D. Vasquez,Chung-Der Hsiao
Simple SummaryIn recent years, the human population on Earth has increased, leading to a higher demand for food sources. Pesticides have emerged as a breakthrough to enhance crop yields. However, the excessive use of pesticides has raised concerns regarding their potential impact on aquatic animals. Thus, this study aims to assess the potential cardiovascular toxicity of various pesticides, with a specific focus on fenpropathrin. When compared to other pesticides, fenpropathrin causes cardiomegaly, an increased heart rate, a significant rise in blood flow velocity, and an elevated metabolism rate. Furthermore, it has been found to bind to several ion channels, inducing alterations in cardiovascular-related markers. These findings indicate that fenpropathrin induces cardiotoxicity in the zebrafish larvae model.AbstractFenpropathrin, a pyrethroid insecticide, has been widely used for many years in agricultural fields. It works by disturbing the voltage-gated sodium channel, leading to paralysis and the death of the target animal. While past studies have focused on neurodegeneration following fenpropathrin poisoning in humans, relatively few pieces of research have examined its effect on other peripheral organs. This study successfully investigated the potential toxicity of fenpropathrin on the cardiovascular system using zebrafish as an animal model. Zebrafish larvae exposed to varying doses of fenpropathrin underwent an evaluation of cardiac physiology by measuring the heart rate, stroke volume, cardiac output, and shortening fraction. The blood flow velocity and the dorsal aorta diameter were also measured to assess the impact of fenpropathrin exposure on the vascular system. Furthermore, molecular docking was performed to evaluate the pesticide binding affinity to various proteins associated with the cardiovascular system, revealing the potential mechanism of the fenpropathrin cardiotoxic effect. The findings demonstrated a significant dose-dependent increase in the heart rate stroke volume, cardiac output, shortening fraction, and ejection fraction of zebrafish larvae after 24 h of acute treatment with fenpropathrin. Additionally, zebrafish treated at a concentration of 1 ppm exhibited significantly larger blood vessels in diameter and an increased blood flow velocity compared to the control group. According to molecular docking, fenpropathrin showed a high affinity for various voltage-gated sodium channels like scn1lab, cacna1sb, and clcn3. Finally, from the results, we found that fenpropathrin caused cardiomegaly, which may have been induced by the voltage-gated sodium channel disruption. This study highlights the significant disruption of fenpropathrin in the cardiovascular system and emphasizes the need for further research on the health implications of this pesticide.Keywords:fenpropathrin;zebrafish;cardiovascular toxicity;pesticide
研究领域:
毒理学
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环境科学
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心血管生物学
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2023
·
IF 4
Chengcheng Jin,Ting Wang,Tingting Zhao,Wen Jiang,Xiaolan Zhen,Hui Li
Objective To determine the concentrations of nine drugs used in the treatment of cardiovascular diseases in human plasma through QuEChERS pre-treatment combined with ultra-performance liquid chromatography-tandem mass spectrometry. Plasma samples were extracted with 3 mL of acetonitrile, 400 mg of anhydrous magnesium sulfate as a salting agent, and 20 mg of C18 as a sorbent. An Agilent Poroshell 120 EC-C18 column (4.6 × 100 mm, 2.7 μm) was selected and methanol-0.1 % water was used as the mobile phase, and ESI positive ion detection mode was selected. Results: The plasma concentrations of nisoldipine, metoprolol, and prazosin exhibited good linearity within the range of 0.05–4.0 ng/mL (r > 0.99), while atenolol, bisoprolol, propranolol, rosuvastatin, and atorvastatin showed linearity within the range of 0.5–40 ng/mL (r > 0.99). Fluvastatin showed good linearity within the range of 5.0–400 ng/mL. The accuracy of the method ranged from 94.15 to 110.62 %, while the recovery levels were in the range of 85.23 %–115.13 %. The matrix effects were observed between-6.54 % and 12.43 %. The intra-day and inter-day RSD was <15 % for the three concentrations of low, medium, and high. Conclusion The proposed method is rapid, accurate, specific, simple, reproducible, and suitable for the simultaneous measurement of the concentrations of nine drugs used in the treatment of cardiovascular diseases in human plasma.
研究领域:
分析化学
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药理学
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临床医学
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DOI
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
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2020
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IF 6.17
Yao-Dan Liang,Qian Liu,Ming-Hui Du,Zhen Liu,Si-Min Yao,Pei-Pei Zheng,Yu-Hao Wan,Ning Sun,Ying-Ying Li,Jun-Peng Liu,Yao Luo,Jian-Ping Cai,Jie-Fu Yang,Hua Wang
The diagnosis of frailty is usually subjective, which calls for objective biomarkers in clinical medicine . 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGsn) and 8-oxo-7, 8-dihydroguanosine (8-oxoGsn) in urine are two aging biomarkers that have not been explored deeply in cases of frailty. A total of 508 elderly patients with cardiovascular disease (mean age 75.0 ± 6.5 years, 50.8% males) were enrolled consecutively. Frailty was assessed by the Fried phenotype (robust: 0 score; pre-frail: 1–2 scores; frail: 3–5 scores). The concentrations of 8-oxoGsn and 8-oxodGsn in urine were measured by improved ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Urinary creatinine (Cre) was tested to correct the 8-oxoGsn and 8-oxodGsn levels. According to the Fried phenotype score, the proportions of robust, pre-frail, and frail subjects were 20.5% (104/508), 53.9% (274/508), and 25.6% (130/508), respectively. The urinary 8-oxoGsn/Cre (P < 0.001) differed significantly among these 3 groups, but the urinary 8-oxodGsn/Cre (P = 0.600) showed no marked difference. Univariate and multivariate logistic regression showed that the age (odds ratio [OR] = 1.090, P < 0.001), systolic blood pressure (OR = 0.981, P = 0.008), 8-oxoGsn/Cre (OR = 1.203, P = 0.007), hemoglobin (OR = 0.980, P = 0.007), and sodium (OR = 0.915, P = 0.044) were independently associated with frailty. The sensitivity and specificity to identify frailty were 53.08% and 71.96%, respectively, for 8-oxoGsn/Cre at the optimal cut-off value of 3.879 μmol/mol according to the maximal Youden index . Urinary 8-oxoGsn, as a recognized biomarker of RNA oxidation , is independently associated with frailty in elderly patients with cardiovascular disease. However, the urinary 8-oxodGsn shows no obvious correlation with frailty. To obtain a better diagnostic performance for frailty, more biomarkers from different pathophysiological pathways should be explored in the future.
研究领域:
老年医学
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临床医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Inventions
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2019
·Vol. 4
·期 4
·65
·
IF 0
Fiorency Santoso,Bonifasius Putera Sampurna,Yu-Heng Lai,Sung-Tzu Liang,Erwei Hao,Jung-Ren Chen,Chung-Der Hsiao
This study aimed to develop a simple and cost-effective method to measure blood flow in zebrafish by using an image-based approach. Three days post fertilization (dpf) zebrafish embryos were mounted with methylcellulose and subjected to video recording for tracking blood flow under an inverted microscope equipped with a high-speed CCD camera. In addition, Hoffman lens was used to enhance the blood cell contrast. The red blood cell movement was tracked by using the TrackMate plug-in in the ImageJ image processing program. Moreover, Stack Difference and Time Series Analyzer plug-in were used to detect dynamic pixel changes over time to calculate the blood flow rate. In addition to blood flow velocity and heart rate, the effect of drug treatments on other cardiovascular function parameters, such as stroke volume and cardiac output remains to be explored. Therefore, by using this method, the potential side effects on the cardiovascular performance of ethyl 3-aminobenzoate methanesulfonate (MS222) and 3-isobutyl-1-methylxanthine (IBMX) were evaluated. MS222 is a common anesthetic, while IBMX is a naturally occurring methylxanthine. Compared to normal embryos, MS222- and IBMX-treated embryos had a reduced blood flow velocity by approximately 72% and 58%, respectively. This study showed that MS222 significantly decreased the heart rate, whereas IBMX increased the heart rate. Moreover, it also demonstrated that MS222 treatment reduced 50% of the stroke volume and cardiac output. While IBMX decreased the stroke volume only. The results are in line with previous studies that used expensive instruments and complicated software analysis to assess cardiovascular function. In conclusion, a simple and low-cost method can be used to study blood flow in zebrafish embryos for compound screening. Furthermore, it could provide a precise measurement of clinically relevant cardiac functions, specifically heart rate, stroke volume, and cardiac output.Keywords:blood flow tracking;ImageJ;zebrafish;IBMX;MS222;cardiovascular function assessment
研究领域:
发育生物学
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毒理学
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产品关联
DOI
JOURNAL OF BIOMATERIALS APPLICATIONS
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2023
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IF 2.9
Zhixing Wang,Peng Liu,Peng Ye,Sheng Dai,LuYing Liu,Ping Yang
Dopamine has been widely used for surface modification of cardiovascular medical devices as it forms films on most substrates that provide functional groups for surface chemical modification. However, under oxidative stress, the phenolic hydroxyl group on dopamine can undergo reversible transformation into phenol-semiquinone-quinone, which can cause cytotoxicity and immunotoxicity. In this study, we measured the effects of semiquinone on the behavior of vascular wall cells and inflammatory cells under oxidative stress via ultraviolet irradiation with a hydrogen peroxide diluent. Na2S2O3 was used as a stabilizer to obtain a semiquinone-rich poly-dopamine film, then phenol-semiquinone-quinone ratio on its surface was evaluated at three irradiation-oxidation time points. We found that the poly-dopamine film with ultraviolet irradiation in hydrogen peroxide solution for 15 min had the highest semiquinone occupancy of 19.18%. In the experimental group irradiated for 15 min, endothelial cells were cultured statically for 3 days and the number of surface adherent endothelial cells in the group with added semiquinone stabilizer was reduced to 73% of that in the group without stabilizer, indicating that semiquinone rich surface inhibits adhesion and proliferation of endothelial cells; Smooth muscle cells were cultured statically for 3 days, and the number of adherent smooth muscle on surfaces without stabilizer was reduced to 75% of that on surfaces with stabilizer added, indicating that semiquinone rich surfaces promote smooth muscle proliferation. These results demonstrate that semiquinone can adversely affect the repair effect after implantation of cardiovascular materials. Therefore, our study provides a reference for the application and optimization of dopamine in cardiovascular implant materials.
研究领域:
生物医学工程
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细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 19
·11711
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IF 6.208
Huan-Chau Lin,Ferry Saputra,Gilbert Audira,Yu-Heng Lai,Marri Jmelou M. Roldan,Honeymae C. Alos,Charlaine A. Aventurado,Ross D. Vasquez,Guan-Jhe Tsai,Ken-Hong Lim,Chung-Der Hsiao
BCR-ABL, a fusion protein kinase, is a druggable target exclusively expressed in patients with chronic myeloid leukemia (CML). Several anti-leukemia medicines targeting this protein have been developed in recent years. However, therapeutic options are limited for CML patients bearing multiple BCR-ABL1 mutations. Ponatinib (PON), a potent tyrosinase inhibitor, was one of the approved drugs for managing BCR-ABL1 T315I mutant disease. However, treatment of patients with PON reported severe side effects related to cardiovascular events. Asciminib (ASC) was the first allosteric inhibitor approved to target the myristoyl pocket of BCR-ABL protein to inhibit protein activity. The different mechanism of inhibition opens the possibility of co-exposure with both medicines. Reports on cardiovascular side effects due to the combination use of PON + ASC in pre-clinical and clinical studies are minimal. Thus, this study aimed to observe the potential cardiovascular-related side effect after co-exposure to ASC and PON using zebrafish as an animal model. In this study, zebrafish were acutely exposed to both compounds. The cardiovascular physiology parameters and gene expression related to cardiovascular development were evaluated. We demonstrate that combining ASC with PON at no observed effect concentration (NOEC) did not cause any significant change in the cardiac performance parameter in zebrafish. However, a significant increase innkx2.5expression level and a substantial decrease in blood flow velocity were recorded, suggesting that combining these compounds at NOEC can cause mild cardiovascular-related side effects.Keywords:zebrafish;anti-cancer drug;asciminib;ponatinib;cardiovascular toxicity;molecular docking
研究领域:
药理学
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毒理学
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发育生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR MEDICINE-JMM
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2025
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IF 4.2
Wen Xin,Peng Yuefeng,Yang Wenqing,Zhu Yuzhong,Yu Fan,Geng Li,Wang Xianfeng,Wang Xiaoyan,Zhang Xiaodong,Tang Yi,Feng Lei,Zhou Tingting,Jia Hongliang,Yang Liu
Transient receptor potential canonical 1 (TRPC1) channel, a Ca 2+ -permeable ion channel widely expressed in vasculature, has been reported to be involved in various cardiovascular disorders. However, the pathophysiological function of vascular smooth muscle cell (VSMC)-derived TRPC1 in hypertension and hypertensive cardiovascular remodeling remains to be defined. In this study, we found increased TRPC1 expression in both angiotensin II (AngII)-treated VSMCs and aortas from AngII-infused mice. VSMC-specific TRPC1 deficiency strikingly attenuated AngII-induced vasoconstriction, hypertension, vascular remodeling, and cardiac hypertrophy. Mechanistically, AngII activated enhancer of zeste homolog 2 (EZH2) to stimulate TRPC1 expression, induced calcium influx and phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK-ERK), which in turn triggered VSMC proliferation and migration and exacerbated hypertension and cardiovascular remodeling. Treatment with EZH2 inhibitor reduced VSMC proliferation and migration and alleviated vasoconstriction and hypertension in AngII-infused mice. Together, we revealed the pathogenic role of the EZH2-TRPC1-MEK/ERK pathway in AngII-induced hypertension and cardiovascular damage. TRPC1 or EZH2 inhibition may represent a desirable therapeutic target for the treatment of hypertension. Key messages
AngII activates AT1R-EZH2-TRPC1 pathway in VSMCs and aortas of hypertensive mice.
TRPC1 promotes VSMC proliferation and migration via MEK/ERK signaling.
Inhibition of TRPC1 or EZH2 alleviates hypertension and cardiovascular remodeling.
研究领域:
心血管病学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Xiuyan He,Wenji Hu,Yao Zu
The widespread presence of antihistamines such as loratadine in aquatic environments poses emerging ecotoxicological concerns, yet their developmental impacts remain poorly characterized. In this study, zebrafish embryos were exposed to loratadine (35–350 μg/L) to evaluate its developmental effects. By 2–3 days post-fertilization (dpf), exposed larvae exhibited marked cardiac defects, including pericardial edema, reduced heart rate and cardiac output, and fractional area change ( p < 0.05). By 4–6 dpf, a complete failure of swim bladder inflation was observed in the exposed group, confirmed by histological analysis showing significantly reduced bladder area ( p < 0.0001). Behavioral assays revealed impaired locomotion, with decreased total distance and swimming speed ( p < 0.001). Molecular analyses showed that loratadine significantly altered the expression of cardiac genes ( acta1b , atp2a2a , gata4 , hand2 , tbx5a ) and suppressed key regulators of swim bladder development ( fgf10a , smo , gli2a , fzd2 , fzd5 , wnt2bb ) ( p < 0.05), ultimately resulting in abnormal cardiac and swim bladder development. These findings highlight the pronounced ecotoxicological impact of loratadine on aquatic vertebrates and reinforce the urgent need for improved environmental surveillance and wastewater remediation strategies to curb pharmaceutical contamination in freshwater ecosystems.
研究领域:
发育生物学
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生态毒理学
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药理学
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环境科学
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产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
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2025
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IF 8.9
Lingyan Li,Xingjie Wu,Qianqian Guo,Yu'e Wang,Zhiyong He,Guangqiong Zhang,Shaobo Liu,Liping Shu,Babu Gajendran,Ying Chen,Xiangchun Shen,Ling Tao
Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma expression in vascular endothelial cells and estrogen receptor alpha protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with cholesterol metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.
研究领域:
药剂学
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生物医学工程
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
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2020
·
IF 5.778
Yongqi Sun,Yi Cao,Lili Tong,Fangyi Tao,Xiaonan Wang,Huiming Wu,Mengcen Wang
Prothioconazole is a fungicide that has been widely used in general agriculture and livestock husbandry. This study evaluated the acute toxicity of prothioconazole to zebrafish embryos by assessing their hatching rate and malformation when exposed to different concentrations of prothioconazole. The 96 h-LC 50 value of zebrafish embryos was 1.70 mg/L. Upon exposure to 0.85 mg/L, the mortality rate of the embryos significantly increased while their hatching rate decreased significantly. At prothioconazole concentrations higher than 0.43 mg/L, developmental morphologic abnormalities such as heart and yolk-sac edema, spine curvature, tail deformity, shortened body length and decreased eye area were observed. The heart rate of embryos decreased in a dose-dependent fashion during the exposure time. Prothioconazole exposure also resulted in increased rates of cardiac malformation detected by significant increase in the distance between the sinus venosus and bulbus arteriosus and the pericardium area. Moreover, the expression levels of genes related to cardiac development ( amhc, vmhc, fli1, hand2, gata4, nkx2.5, tbx5 and atp2a2a ) were significantly altered after exposure to prothioconazole. Indeed, this study revealed the adverse effects on the developmental and cardiovascular system of zebrafish embryo caused by prothioconazole. It further elucidated the risk of prothioconazole exposure to vertebrate cardiovascular toxicity. As such, it provides a theoretical foundation for pesticide risk management measures.
研究领域:
毒理学
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环境科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2024
·
IF 8
Bo Bao,Xinran Tian,Ridong Wang,Dachao Li
As cardiovascular diseases (CVDs) are the leading cause of death worldwide, it is of great importance to realize a rapid and sensitive diagnosis. Multiple CVD biomarker detection, which holds higher accuracy and speed of early CVD diagnosis, is becoming a promising alternative to single biomarker analysis. Cardiac troponin I (cTnI), C-reactive protein (CRP), brain-type natriuretic peptide (BNP), and heart fatty acid binding protein (H-FABP) are four significant diagnostic biomarkers for CVDs. Among the several methods for biomarker detection, such as optical, magnetic, mechanical, and electrical methods, the magnetic method stands out because of its stability, low toxicity, noninvasive detection, facile manipulation with an external magnetic field, and immunity to the interference of background light. At present, the lack of multiplexing capability, the imprecision of magnetic signal localization, and the agglomeration and non-specific adsorption of magnetic nanoparticles all limit the clinical application of magnetic detection. This paper presented a novel method for multiple CVD biomarker detection using a spin exchange relaxation-free (SERF)-based microfluidic platform. One or more SERF atomic magnetometers were used to scan the remanent field of magnetic labels to detect four CVD biomarkers in 70 min, with a detection limit of 1.88 pg/mL (cTnI), 1.58 pg/mL (CRP), 1.45 pg/mL (BNP), and 1.71 pg/mL (H-FABP). The results showed two-dimensional magnetic fields with a resolution of submillimeter level and a sensitivity of pT level. The measurement technique provides a new magnetic methodology for applications in clinical diagnosis.
研究领域:
医学诊断
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生物医学工程
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产品关联
DOI
高影响因子
MICROCHEMICAL JOURNAL
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2021
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IF 4.821
Wenxiang Xiao,Zhenzhen Yang,Jing Liu,ZhenCheng Chen,Hua Li
As one of the most important biomarkers for cardiovascular disease and high blood pressure, cholesterol quantification is of great importance for clinical diagnosis and health management. In this study, mercapto-β-cyclodextrin capped gold nanoclusters have been used as fluorescent probes for succinct and sensitive determination of cholesterol. Using mercapto-β-cyclodextrin as a reducing and capping agent, gold nanoclusters with bluish-green fluorescence were synthesized by the one-pot hydrothermal method. The cyclodextrin cavities of the capping layer on gold nanoclusters act as selective units for cholesterol recognition, and the gold cores serve as signal reporting units. The host–guest interaction between cholesterol and cyclodextrin directly enhances the fluorescence of gold nanoclusters without the involvement of additional dyes or quenchers. Under the optimal conditions, the probe responds linearly to cholesterol in the concentration range of 10.0 ∼ 100.0 μmol·L -1 with the detection limit of 5.77 ± 0.18 μmol·L -1 (3σ, n = 3). Common coexisting components in the serum did not interfere with the detection of cholesterol. Satisfactory results were obtained for the determination of cholesterol in real serum samples by the proposed method.
研究领域:
分析化学
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生物医学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）