Zebrafish
·
2019
·Vol. 16
·期 5
·434-442
·
IF 1.742
Xiaoyan Zou,Qiuyan Liu,Songchang Guo,Junyi Zhu,Jichun Han,Zhenjiang Xia,Yuzhi Du,Lixin Wei,Jing Shang
Strategies to reduce reperfusion injury after ischemia have been considered in clinical practice, but few interventions have successfully passed the proof-of-concept stage. In this study, we developed a novel zebrafish larvae hypoxia/reoxygenation (H/R) model to simulate myocardial ischemia/reperfusion injury (MIRI), with potential utility as a drug screening tool. After H/R treatment, videos of transgenic [Tg(cmlc:EGFP)] larval zebrafish hearts were captured using a digital high-speed camera, and the heart rate, diastolic area, systolic area, and total fraction of area changed were quantified. The mRNA expression of tnnt2, bnp, and hif1α was quantified, and red blood cells (RBCs) were detected by O-dianisidine staining. We found that a decline in cardiac contractility occurred in zebrafish larvae 48 h after hypoxia treatment. Reoxygenation for 2–5 h after 48 h of hypoxia caused heart dysfunction in zebrafish larvae, and were determined to be the optimum conditions for simulating MIRI similar to mammalian models. Our results indicated that heart dysfunction after reoxygenation in zebrafish larvae was accompanied by an upregulated gene expression of a number of myocardial injury biomarkers and increased numbers of RBCs. In conclusion, the novel larval zebrafish H/R model developed in this study could be used for rapid in vivo screening and efficacy assessment of MIRI therapeutics.
研究领域:
心脏病学
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药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
World Journal of Gastrointestinal Surgery
·
2023
·
IF 2
Fan Ding,Run Guo,Fang Chen,Li-Ping Liu,Zheng-Yu Cui,Yi-Xing Wang,Gang Zhao,Hai Hu
BACKGROUND Impaired interstitial cells of Cajal (ICCs) are central to the pathophysiology of acute cholecystitis (AC). Common bile duct ligation is a common model of AC, producing acute inflammatory changes and decrease in gallbladder contractility. AIM To investigate the origin of slow wave (SW) in the gallbladder and the effect of ICCs on gallbladder contractions during the process of AC. METHODS Methylene blue (MB) with light was used to establish selective impaired ICCs gallbladder tissue. Gallbladder motility was assessed using the frequency of SW and gallbladder muscle contractility in vitro in normal control (NC), AC12h, AC24h, and AC48h groups of guinea pigs. Hematoxylin and eosin and Masson-stained gallbladder tissues were scored for inflammatory changes. ICCs pathological changes alterations were estimated using immunohistochemistry and transmission electron microscopy. The alterations of c-Kit, α-SMA, cholecystokinin A receptor (CCKAR), and connexin 43 (CX43) were assessed using Western blot. RESULTS Impaired ICCs muscle strips resulted in the decrease in gallbladder SW frequency and contractility. The frequency of SW and gallbladder contractility were significantly lower in the AC12h group. Compared with the NC group, the density and ultrastructure of ICCs were remarkably impaired in the AC groups, especially in the AC12h group. The protein expression levels of c-Kit were significantly decreased in the AC12h group, while CCKAR and CX43 protein expression levels were significantly decreased in the AC48h group. CONCLUSION Loss ICCs could lead to a decrease in gallbladder SW frequency and contractility. The density and ultrastructure of ICCs were clearly impaired in the early stage of AC, while CCKAR and CX43 were significantly reduced at end stage.
研究领域:
胃肠病学
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生理学
·
病理生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2023
·
IF 5.8
Xiaoning Han,Lele Xu,Ting Dou,Rong Du,Linhong Deng,Xiang Wang
Cell-generated contraction force is the primary physical drive for fibrotic densification of biological tissues. Previous studies using two-dimensional culture models have shown that epithelial cells inhibit the myofibroblast-derived contraction force via the regulation of the fibroblast/myofibroblast transition (FMT). However, it remains unclear how epithelial cells interact with fibroblasts and myofibroblasts to determine the mechanical consequences and spatiotemporal regulation of fibrosis development. In this study, we established a three-dimensional microtissue model using an NIH/3T3 fibroblast-laden collagen hydrogel, incorporated with a microstring-based force sensor, to assess fibrosis mechanics. When Madin–Darby canine kidney epithelial cells were cocultured on the microtissue’s surface, the densification, stiffness, and contraction force of the microtissue greatly decreased compared to the monocultured microtissue without epithelial cells. The key fibrotic features, such as enhanced protein expression of α-smooth muscle actin, fibronectin, and collagen indicating FMT and matrix deposition, respectively, were also significantly reduced. The antifibrotic effects of epithelial cells on the microtissue were dependent on the intercellular signaling molecule prostaglandin E2 (PGE2) with an effective concentration of 10 μM and their proximity to the fibroblasts, indicating paracrine cellular signaling between the two types of cells during tissue fibrosis. The effect of PGE2 on microtissue contraction was also dependent on the time point when PGE2 was delivered or blocked, suggesting that the presence of epithelial cells at an early stage is critical for preventing or treating advanced fibrosis. Taken together, this study provides insights into the spatiotemporal regulation of mechanical properties of fibrosis by epithelial cells, and the cocultured microtissue model incorporated with a real-time and sensitive force sensor will be a suitable system for evaluating fibrosis and drug screening.
研究领域:
生物医学工程
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细胞生物学
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组织工程
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LAB ON A CHIP
·
2015
·Vol. 15
·期 17
·3481-3494
·
IF 6.115
Hui Zhao,Lyu Zhou,Qiang Zhang,Xiaoying Zhou,Yonghui Zhang,Huijun Chen,Yanan Du
Phenotypic screening has regained momentum in the pharmaceutical industry owing to its success over target-based screening. Most phenotypic screening relies on nonspecific biochemical readouts regarding cellular viability, which hampers the discovery of novel drug mechanisms of action (MOAs). Here we present a Contractility-based bi-Content micro-Collagen Chip (3CChip), which establishes cellular contractility as a biomechanics-related phenotype for drug screening. Bi-content analysis of cell contractility (imaged by iPhone) and viability suggests that the label-free contractility-based analysis exhibits superior sensitivity to compounds targeting contractile elements (e.g. focal adhesion, cytoskeleton), resulting in a enlarged target pool for drug assessment. Six typical readout patterns of drug response are summarized according to the relative positions of the contraction/viability curves, and drug targets are profiled into three categories (biomechanical, biochemical and housekeeping) by 3CChip, which will benefit subsequent target identification. The simple-to-use and effective 3CChip offers a robust platform for micro-tissue-based functional screening and may lead to a new era of mechanism-informed phenotypic drug discovery.
研究领域:
药学
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生物医学工程
·
细胞生物学
·
药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Cardiovascular Translational Research
·
2022
·Vol. 16
·期 1
·127-140
·
IF 3.216
Hao Jiameng,Chang Liping,Wang Dandong,Ji Chuanyuan,Zhang Shaolan,Hou Yunlong,Wu Yiling
Heart failure with preserved ejection fraction (HFpEF) is a common public health problem associated with increased morbidity and long-term mortality. However, effective treatment for HFpEF was not discovered yet. In the present study, we aimed to decipher the effects of Periplocin on DOCA-induced heart failure rats and explore the possible underlying mechanisms. We demonstrated that Periplocin could significantly attenuate cardiac structural remodeling and improve cardiac diastolic function. Of note, Periplocin significantly inhibited the recruitment of inflammatory and immune cells and decreased the expression of serum inflammatory cytokines. Meanwhile, Periplocin had the effect of cardiac glycosides to improve cardiomyocyte contractility and calcium transient amplitude. These findings indicate that Periplocin might be a potential medicine to treat HFpEF in patients. Graphical abstract
研究领域:
心脏病学
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药理学
·
炎症
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
WORLD JOURNAL OF GASTROENTEROLOGY
·
2012
·
IF 2.471
Da-Peng Chen,Yong-Jian Xiong,Ze-Yao Tang,Qi-Ying Yao,Dong-Mei Ye,Sha-Sha Liu,Yuan Lin
AIM: To characterize the dual effects of deslanoside on the contractility of jejunal smooth muscle. METHODS: Eight pairs of different low and high contractile states of isolated jejunal smooth muscle fragment (JSMF) were established. Contractile amplitude of JSMF in different low and high contractile states was selected to determine the effects of deslanoside, and Western blotting analysis was performed to measure the effects of deslanoside on myosin phosphorylation of jejunal smooth muscle. RESULTS: Stimulatory effects on the contractility of JSMF were induced (45.3% ± 4.0% vs 87.0% ± 7.8%, P < 0.01) by deslanoside in 8 low contractile states, and inhibitory effects were induced (180.6% ± 17.8% vs 109.9% ± 10.8%, P < 0.01) on the contractility of JSMF in 8 high contractile states. The effect of deslanoside on the phosphorylation of myosin light chain of JSMF in low (78.1% ± 4.1% vs 96.0% ± 8.1%, P < 0.01) and high contractile state (139.2% ± 8.5% vs 105.5 ± 7.34, P < 0.01) was also bidirectional. Bidirectional regulation (BR) was abolished in the presence of tetrodotoxin. Deslanoside did not affect jejunal contractility pretreated with the Ca 2+ channel blocker verapamil or in a Ca 2+ -free assay condition. The stimulatory effect of deslanoside on JSMF in a low contractile state (low Ca 2+ induced) was abolished by atropine. The inhibitory effect of deslanoside on jejunal contractility in a high contractile state (high Ca 2+ induced) was blocked by phentolamine, propranolol and L-NG-nitro-arginine, respectively. CONCLUSION: Deslanoside-induced BR is Ca 2+ dependent and is related to cholinergic and adrenergic systems when JSMF is in low or high contractile states.
研究领域:
药理学
·
胃肠生理学
✓ 已验证
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2014
·
IF 1.337
Dapeng Chen,Yongjian Xiong,Chunling Jiang,Bochao Lv,Fangfei Liu,Li Wang,Yuan Lin
Context: Ginsenosides are primary active ingredients of ginseng, which are believed to have various health benefits. It is found that the biotransformation of ginsenosides mainly takes place in the gastrointestinal tract and the information about ginsenosides-exerted effects on intestinal contractility is not sufficient.Aims: The present study proposed that ginsenosides could exert stimulatory or inhibitory effects on intestinal motility depending on the assay condition-related intestinal contractile states and was to characterize the effects of ginsenosides on intestinal motility.Methods: Jejunal contractility determination, Western blotting analysis, and real-time polymerase chain reaction were performed to test the effects of total ginsenosides isolated from Panax ginseng C. A. Mey (Araliaceae) root.Results: The results showed that ginsenosides at the fixed concentration of 20 mg/L exerted bidirectional regulation (BR) on the contractility of isolated jejunal segment (IJS), depending on the contractile states. The contractility of IJS was increased by ginsenosides in low contractile states, which were correlated to the cholinergic activation, and the contractility of IJS was decreased by ginsenosides in high contractile states, which were correlated to the adrenergic activation and nitric oxide related mechanisms. Ginsenosides-induced BR was abolished in the absence of Ca2+ or by using tetrodotoxin, implicating the requirement of Ca2+ and the enteric nervous system. Effects of ginsenosides on myosin light chain phosphorylation and the mRNA expression of myosin light chain kinase were also bidirectional.Discussion and conclusion: Results suggest that ginsenosides may have the potential clinical implication for reliving the symptoms of alternative hypo- and hyper-intestinal motility.
研究领域:
药理学
·
胃肠病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
FITOTERAPIA
·
2014
·
IF 2.216
Yong-Jian Xiong,Da-Peng Chen,Bo-Chao Lv,Fang-Fei Liu,Li Wang,Yuan Lin
Nobiletin , a citrus polymethoxylated flavone , exhibits multiple biological properties including anti-inflammatory, anti-carcinogenic, and anti-insulin resistance effects. The present study found that nobiletin exerted significant stimulatory effects on the contractility of isolated rat jejunal segments in all 6 different low contractile states, and meanwhile significant inhibitory effects in all 6 different high contractile states, showing characteristics of bidirectional regulation (BR). Nobiletin-exerted BR on jejunal contractility was abolished in the presence of c-kit receptor tyrosine kinase inhibitor imatinib or Ca 2 + channel blocker verapamil . In the presence of neuroxin tetrodotoxin , nobiletin only exerted stimulatory effects on jejunal contractility in both low and high contractile states. Hemicholinium-3 and atropine partially blocked nobiletin-exerted stimulatory effects on jejunal contractility in low-Ca 2 + -induced low contractile state. Phentolamine or propranolol or l -NG-nitro-arginine significantly blocked nobiletin-exerted inhibitory effects on jejunal contractility in high-Ca 2 + -induced high contractile state respectively. The effects of nobiletin on myosin light chain kinase (MLCK) mRNA expression, MLCK protein content, and myosin light chain phosphorylation extent were also bidirectional. In summary, nobiletin-exerted BR depends on the contractile states of rat jejunal segments. Nobiletin-exerted BR requires the enteric nervous system, interstitial cell of Cajal, Ca 2 + , and myosin phosphorylation-related mechanisms.
研究领域:
药理学
·
胃肠病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2019
·
IF 13.903
Chen Song,Xingying Zhang,Leyu Wang,Feng Wen,Kaige Xu,Weirong Xiong,Chuangkun Li,Bingyun Li,Quan Wang,Malcolm M. Q. Xing,Xiaozhong Qiu
Designing scaffolds with persistent elasticity and conductivity to mimic microenvironments becomes a feasible way to repair cardiac tissue. Injectable biomaterials for cardiac tissue engineering have demonstrated the ability to restore cardiac function by preventing ventricular dilation, enhancing angiogenesis, and improving conduction velocity. However, limitations are still among them, such as poor mechanical stability, low conductivity, and complicated procedure. Here, we developed thermal plastic poly(glycolic acid) surgical suture and mussel-inspired conductive particle’s adhesion into a highly elastic, conductive spring-like coils. The polypyrrole (PPy)-coated biospring acted as an electrode and then was assembled into a solid-state supercapacitor. After being injected through a syringe needle (0.33 mm inner diameter), the tangled coils formed an elastically conductive three-dimensional (3-D) network to modulate cardiac function. We found that cardiomyocytes (CMs) grew along the spring coils’ track with elongated morphologies and formed highly oriented sarcomeres. The biospring enhanced the CMs’ maturation in synchronous contraction accompanied by high expressions of cardiac-specific proteins, α-actinin, and connexin 43 (cx43). After the elastic, conductive biosprings were injected into the myocardial infarction (MI) area, the left ventricular fractional shortening was improved by about 12.6% and the infarct size was decreased by about 34%. Interestingly, the spring can be utilized as a sensor to measure the CMs’ contractile force, which was 1.57 × 10–3 ± 0.26 × 10–3 mN (∼4.1 × 106 cells). Accordingly, this study highlights an injectable biospring to form a tangled conductive 3-D network in vivo for MI repair.
研究领域:
生物医学工程
·
材料科学
·
心脏病学
·
组织工程
✓ 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）