Drug Design Development and Therapy
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2022
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IF 4.319
Deshan Yao,Bo Shi,Sichuan Wang,Liuxiang Bao,Meng Tan,Hui Shen,Zhengang Zhang,Xin Pan,Yi Yang,Yong Wu,Kaizheng Gong
Background Oxidative stress and inflammatory reaction play critical roles in acute myocardial infarction (AMI). Isoliquiritigenin (ISL), a flavonoid monomer extracted from licorice, has been found to have antioxidant and anti-inflammatory effects in cancer studies. Here, we tested the effect and underlying mechanisms of ISL on ischemia-induced myocardial injury in a mouse AMI model. Methods Adult C57BL/6 mice were pre-treated by intraperitoneal injection of ISL and/or a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor ML385 for 3 days, respectively. Then, the AMI model was established by ligating the anterior descending branch of the left coronary artery. Myocardial oxidative stress status, inflammatory response, cardiac function and infarction size were assessed after 7th day of surgery. Results Compared with sham group, the reactive oxygen species (ROS) and malondialdehyde (MDA) level in AMI group were significantly increased. However, the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) level were dramatically decreased. ISL treatment significantly reduced the myocardial infarction area, improved cardiac function, inhibited the production of ROS and MDA and reduced the consumption of SOD and GSH-Px. Interestingly, ISL could significantly increase nuclear Nrf2 and cytosolic heme oxygenase 1 (HO-1) level in the infarcted myocardium and reduce the oxidative stress after AMI. Also, ISL treatment dramatically inhibited the activation of myocardial NF-κB pathway and reduced the expression of pro-inflammatory factors in the AMI group. However, the administration of ML385 not only suppressed the Nrf2/HO-1 activation, the anti-oxidant and anti-inflammatory effects induced by ISL, but also attenuated the beneficial role of ISL on reducing infarct size and improving cardiac function in the mouse with AMI. Conclusion The results suggested that activation of Nrf2/HO-1 pathway has an essential role in ISL-induced cardiac protection by alleviating myocardial oxidative stress and inflammation response in mice with AMI.
研究领域:
药理学
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心脏病学
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分子生物学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
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2024
·Vol. 29
·期 1
·1-10
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IF 2.8
Liu Jianlong,Tian Qingxin,Zhang Mingxiao
Myocardial Infarction (MI) is major cause of heart failure, highlighting the critical need for effective therapeutic strategies to improve cardiac repair. This study investigated the cardioprotective effects of VX765-coated polyethyleneimine (PEI)/sodium alginate (AG) composite nanogels (AG/PEI-VX765 NGs) in a rat model of MI. Additionally, AG-VX765 NGs and PEI-VX765 nanospheres (NPs) were synthesized and tested to compare their efficacy. MI was caused in rats by ligating the left anterior descending branch of the coronary artery, and the rats were grouped and set as Sham, MI, MI + VX765, MI + AG-VX765NGs, MI + PEI-VX765NPs, and MI + AG/PEI-VX765NGs. Results demonstrate that AG/PEI-VX765NGs were non-toxic and exhibited a sustained release of VX765. In vivo, experiments demonstrated that all treatment groups significantly enhanced cardiac function, reduced infarct size, fibrosis, and apoptosis in rats with MI, with the MI + AG/PEI-VX765NGs group exhibiting the most favorable outcomes. Our findings indicate that AG/PEI-VX765NGs represent a promising therapeutic approach for MI treatment.
研究领域:
纳米技术
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心脏病学
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药学
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生物医学工程
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药物递送
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DOI
高影响因子
Frontiers in Pharmacology
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2025
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IF 4.8
Yuming Zhai,Jiamei Fu,Jianfei Yang,Yabin Zhou
Background: Myocardial infarction (MI) is characterized by high morbidity. In this study, we aimed to elucidate potential targets of Shengxian Decoction (SXD) against MI.Methods: Pairing of SXD active ingredients and MI targets was conducted using the Chinese Medicine System Pharmacological Database, Gene Expression Omnibus (GEO), and STRING databases. The effects of SXD on MI were validated in vitro. Molecular docking was verified using cellular thermal shift assay (CETSA).Results: A total of 40 active ingredients and 28 MI-related targets were obtained. Cross-analysis on 28 targets and cell death-related genes identified two crucial ferroptosis-related targets, namely, dipeptidyl peptidase 4 (DPP4) and heme oxygenase 1 (HMOX1). In cobalt chloride (CoCl2)-induced hypoxic H9c2 cells, SXD could remarkably improve cell viability and inhibit cell death. Meanwhile, SXD treatment significantly affected the ferroptosis-related markers in hypoxic H9c2 cells. Molecular docking and CETSA results showed that quercetin had good binding activity with DPP4 and HMOX1.Conclusion: Important active ingredient quercetin in SXD could exert anti-ferroptosis protective roles on MI through targeting ferroptosis-related genes (DPP4/HMOX1), thereby contributing to the protective role of SXD on MI.
研究领域:
药理学
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分子生物学
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心血管病学
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DOI
PubMed
高影响因子
Theranostics
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2019
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IF 8.063
Kaiqi Lv,Qingju Li,Ling Zhang,Yingchao Wang,Zhiwei Zhong,Jing Zhao,Xiaoxiao Lin,Jingyi Wang,Keyang Zhu,Changchen Xiao,Changle Ke,Shuhan Zhong,Xianpeng Wu,Jinghai Chen,Hong Yu,Wei Zhu,Xiang Li,Ben Wang,Ruikang Tang,Jian'an Wang,Jinyu Huang,Xinyang Hu
Bone marrow mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) have been widely used for treating myocardial infarction (MI). However, low retention and short-lived therapeutic effects are still significant challenges. This study aimed to determine whether incorporation of MSC-derived sEVs in alginate hydrogel increases their retention in the heart thereby improving therapeutic effects. Methods: The optimal sodium alginate hydrogel incorporating sEVs system was determined by its release ability of sEVs and rheology of hydrogel. Ex vivo fluorescence imaging was utilized to evaluate the retention of sEVs in the heart. Immunoregulation and effects of sEVs on angiogenesis were analyzed by immunofluorescence staining. Echocardiography and Masson's trichrome staining were used to estimate cardiac function and infarct size. Results: The delivery of sEVs incorporated in alginate hydrogel (sEVs-Gel) enhanced their retention in the heart. Compared with sEVs only treatment (sEVs), sEVs-Gel treatment significantly decreased cardiac cell apoptosis and promoted the polarization of macrophages at day 3 after MI. sEVs-Gel treatment also increased scar thickness and angiogenesis at four weeks post-infarction. Measurement of cardiac function and infarct size were significantly better in the sEVs-Gel group than in the group treated with sEVs only. Conclusion: Delivery of sEVs incorporated in alginate hydrogel provides a novel approach of cell-free therapy and optimizes the therapeutic effect of sEVs for MI.
研究领域:
心脏病学
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干细胞生物学
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组织工程
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治疗递送系统
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DOI
PubMed
高影响因子
Frontiers in Cardiovascular Medicine
·
2021
·
IF 6.05
Aa Nan,Lu Ying,Yu Mengjie,Tang Heng,Lu Zhenyao,Sun Runbing,Wang Liansheng,Li Chunjian,Yang Zhijian,Aa Jiye,Kong Xiangqing,Wang Guangji
Myocardial infarction (MI) is one of the leading causes of death worldwide, and knowing the early warning signs of MI is lifesaving. To expand our knowledge of MI, we analyzed plasma metabolites in MI and non-MI chest pain cases to identify markers for alerting about MI occurrence based on metabolomics. A total of 230 volunteers were recruited, consisting of 146 chest pain patients admitted with suspected MI (85 MIs and 61 non-MI chest pain cases) and 84 control individuals. Non-MI cardiac chest pain cases include unstable angina (UA), myocarditis, valvular heart diseases, etc. The blood samples of all suspected MI cases were collected not longer than 6 h since the onset of chest pain. Gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry were applied to identify and quantify the plasma metabolites. Multivariate statistical analysis was utilized to analyze the data, and principal component analysis showed MI could be clearly distinguished from non-MI chest pain cases (including UA and other cases) in the scores plot of metabolomic data, better than that based on the data constructed with medical history and clinical biochemical parameters. Pathway analysis highlighted an upregulated methionine metabolism and downregulated arginine biosynthesis in MI cases. Receiver operating characteristic curve (ROC) and adjusted odds ratio (OR) were calculated to evaluate potential markers for the diagnosis and prediction ability of MI (MI vs. non-MI cases). Finally, gene expression profiles from the Gene Expression Omnibus (GEO) database were briefly discussed to study differential metabolites' connection with plasma transcriptomics. Deoxyuridine (dU), homoserine, and methionine scored highly in ROC analysis (AUC > 0.91), sensitivity (>80%), and specificity (>94%), and they were correlated to LDH and AST (p < 0.05). OR values suggested, after adjusting for gender, age, lipid levels, smoking, type II diabetes, and hypertension history, that high levels of dU of positive logOR = 3.01, methionine of logOR = 3.48, and homoserine of logOR = 1.61 and low levels of isopentenyl diphosphate (IDP) of negative logOR = −5.15, uracil of logOR = −2.38, and arginine of logOR = −0.82 were independent risk factors of MI. Our study highlighted that metabolites belonging to pyrimidine, methionine, and arginine metabolism are deeply influenced in MI plasma samples. dU, homoserine, and methionine are potential markers to recognize MI cases from other cardiac chest pain cases after the onset of chest pains. Individuals with high plasma abundance of dU, homoserine, or methionine have increased risk of MI, too.
研究领域:
医学
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生物化学
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心血管病学
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DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
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2024
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IF 3.8
Feng-Xia Qu,Xiao Guo,Xiao-Jun Liu,Shu-Wen Zhang,Yue Xin,Jing-Yuan Li,Rong Wang,Chen-Ji Xu,Hai-Ying Li,Chang-Hong Lu
Myocardial infarction (MI) is the primary source of death in cardiovascular diseases. Myricitrin (MYR) is a phenolic compound known for its antioxidant properties. This study aimed to investigate the impact of MYR alone or combined with exercise on a rat model of MI and its underlying mechanism. Sprague-Dawley rats were randomized into 5 groups: sham-operated (Sham), MI-sedentary (MI-Sed), MI-exercise (MI-Ex), MI-sedentary + MYR (MI-Sed-MYR) and MI-exercise + MYR (MI-Ex-MYR). MI was induced through ligation of left anterior descending coronary artery. The treatment with exercise or MYR (30 mg/kg/d) gavage began one week after surgery, either individually or in combination. After 8 weeks, the rats were assessed for cardiac function. Myocardial injuries were estimated using triphenyltetrazolium chloride, sirius red and Masson staining. Changes in reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), apoptosis and Nrf2/HO-1 pathway were analyzed by ROS kit, JC-1 kit, TUNEL assay, western blot and immunohistochemistry. Both MYR and exercise treatments improved cardiac function, reduced infarct size, suppressed collagen deposition, and decreased myocardial fibrosis. Additionally, both MYR and exercise treatments lowered ROS production induced by MI, restored ΔΨm, and attenuated oxidative stress and apoptosis in cardiomyocytes. Importantly, the combination of MYR and exercise showed greater efficacy compared to individual treatments. Mechanistically, the combined intervention activated the Nrf2/HO-1 signaling pathway. These findings suggest that the synergistic effect of MYR and exercise may offer a promising therapeutic approach for alleviating MI.
研究领域:
心脏病学
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药理学
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运动科学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2025
·
IF 5.2
Jing Wang,Congcong Lin,Xiaoyang Li,Junyao Wei,Yihua Wang,Rongtao Li,Yan Ming,Jingling Tang,Jiaxin Liu,Manjie Zhang,Hongyu Ji
Myocardial infarction (MI) is a leading cause of heart failure and death in cardiovascular diseases. Most drug trials currently fail due to inadequate local drug activity and side effects. In this study, we developed a novel polydopamine (PDA) nano delivery system that carries sodium ferulate (SF) and is modified with RGD peptides (SF/RGD-PDA NPs) for precise targeted delivery. SF is a clinical adjuvant for cardiovascular and cerebrovascular diseases but lacks targeting and has a short half-life. PDA, known for its excellent biocompatibility and surface modifiability, serves as an effective carrier. SF was loaded onto PDA through π-π stacking, while RGD was attached via a Michael addition reaction, resulting in stable SF/RGD-PDA NPs with an average particle size of 206.13 nm. In vitro and in vivo studies indicate that this targeted formulation has good safety. Targeting studies showed a 2.19-fold increase in nanoparticle accumulation in the heart and a 5.94-fold increase in cellular uptake efficiency. Pharmacodynamic studies revealed a 1.45-fold increase in endothelial cell proliferation, a 1.46-fold increase in angiogenesis rate, and a significant reduction in MI area. These findings suggest that SF/RGD-PDA NPs can improve endothelial cell function and reduce MI area through targeted delivery.
研究领域:
药学
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心血管病学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL NEUROLOGY
·
2021
·
IF 5.33
Mengmeng Wang,Ying Bai,Haitao Chi,Ping Lin,Yu Wu,Jiahui Cui,Yi Wang,Jing Sun,Ming-Fei Lang
Ischemic stroke still remains a therapeutic challenge due to its complex pathogenesis and implications. By screening biomarkers in the peripheral blood of ischemic stroke patients , miR-451 was identified as a differentially expressed miRNA along the disease course of ischemic stroke. To investigate the role of miR-451, middle cerebral artery occlusion (MCAO) was performed as an ischemic stroke model in mice. Intracerebroventricular administration of miR-451 mimic in the MCAO mice significantly decreased infarct size, while miR-451 inhibitor significantly increased infarct size. To understand the molecular mechanism of the protective effect of miR-451, Phd3 (also Egln3) was validated as a new miR-451 target. Either fewer or more Phd3-positive cells were observed in brain sections from mice receiving miR-451 mimic or inhibitor, respectively. In addition, the levels of p53 (a known Phd3 target) were significantly downregulated when the levels of Phd3 were reduced, suggesting its participation in reducing apoptosis after the miR-451 administration. Indeed, reduced apoptosis upon miR-451 mimic administration was detected by TUNEL staining . In conclusion, this study demonstrated a new protective role of miR-451 in cerebral ischemia and identified Phd3 as a novel miR-451 target, linking the mechanism to the involvement of p53 in the regulation of apoptosis during the pathogenesis of ischemic stroke.
研究领域:
神经科学
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分子生物学
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医学遗传学
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DOI
PubMed
高影响因子
REACTIVE & FUNCTIONAL POLYMERS
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2022
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IF 4.966
Xiao Li Li,Peng Liu,Bin Chu,Jin Mei He,Zhen Wang,Song Wang,Chang Sheng Chen,Xiao Hong Ge,Hui Li,Wei Qiang Liu
Myocardial infarction (MI) is a common heart emergency that potentially causes death. Injectable hydrogels with excellent malleability and filling properties are suitable for myocardial injection and can avoid the need for open surgery. In this study, dopamine grafted hyaluronic acid (HADOPA) was synthesized and combined with sodium alginate (Alg) and Ca 2+ -loaded liposomes (Ca-FVI) to prepare a series of injectable thermosensitive sodium hyaluronate/sodium alginate hydrogels (HADOPA/Ca-FVI/Alg). At 37 °C, the HADOPA/Ca-FVI/Alg solution rapidly changed from liquid to hydrogel because of the crosslinking between sodium alginate and the Ca 2+ released from Ca-FVI at a phase transition time of 100–200 s. The HADOPA/Ca-FVI/Alg scaffolds exhibited a porous 3D network structure, controlled porosity, and connected pore properties. Increasing the proportion of HADOPA increases the elasticity and absorbance of hydrogels. Experimental assessment showed that the hydrogels have good biocompatibility and that Alg1-HADOPA is more conducive to the adhesion, proliferation, and spreading of mouse cardiac myocytes while maintaining the best cell state. These findings suggest that HADOPA/Ca-FVI/Alg hydrogels improve cell proliferation and tissue repair, and that they are a promising therapeutic option for cardiac repair after MI.
研究领域:
生物材料学
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心血管医学
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DOI
高影响因子
BIOMACROMOLECULES
·
2025
·
IF 5.4
Shan Yu,Ling Wang,Mengdie Chen,Yanjun Chen,Zhenbo Peng
Myocardial infarction (MI) remains one of the leading causes of mortality worldwide, necessitating advanced therapeutic strategies to address the resulting electrical disconnection and pathological remodeling. This study developed a conductive hydrogel by covalently cross-linking silk fibroin and hyaluronic acid, integrating MXene nanosheets to mimic the extracellular matrix (ECM). Results demonstrated that the incorporation of MXene significantly enhanced the hydrogel’s conductivity, with SH-M5 exhibiting the highest conductivity of 0.32 S/m. The SH-M5 hydrogel effectively improved electrical signal transmission and enhanced the recovery of the left ventricular function in myocardial infarction. These findings underscore the transformative role of MXene in enhancing the functional properties of hydrogels for myocardial repair. The conductive hydrogel demonstrated a unique capacity to integrate mechanical reinforcement, electrical conductivity, and biocompatibility, presenting a promising platform for treating myocardial infarction and advancing regenerative medicine.
研究领域:
生物材料学
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心血管医学
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再生医学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Wenwu Zhu,Yao Lu,Bin Zong,Ziyi Chen,Yong Ma,Haoran Wang,Peng Cao,Bing Han
The ideal treatment for myocardial infarction should address the critical issues of oxygen supply improvement in the infarcted area and prevention of myocardial cell death. Myocardial necrosis is a reversible process, but the challenge lies in mitigating the irreversible pyroptosis of cardiomyocytes, which significantly impedes the recovery of cardiac function. To tackle these complexities, here we have developed MnO2@INN@Alb (MIA) nanoparticles. MIA nanoparticles possess the unique ability to generate oxygen and release glibenclamide (INN) in response to the acidic and H2O2-rich environments present in the infarcted region. MIA plays a dual role by inhibiting the pyroptosis process of cardiomyocytes through the suppression of NLRP3 and by providing vital oxygen to alleviate hypoxia. The results shows that MIA can effectively reverse cardiomyocyte hypoxia, reduce infarct fibrosis, and aid in the reconstruction of myocardial vessels. Moreover, MIA demonstrates high biocompatibility, making it a promising avenue for the future of myocardial infarction improvement. We anticipate that MIA can pave the way for novel solutions and research paradigms in the field.
研究领域:
生物学
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医学
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药理学
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生物材料
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2024
·
IF 2.3
Yunjie Ni,Yinjian Hua,Zhengfei He,Weilv Hu,Zhiyun Chen,Diqing Wang,Xintong Li,Yanfang Sun,Guohua Jiang
Myocardial infarction (MI) is considered as a significant cause of death globally. Exosomes (EXOs) are essential for intercellular communication and pathophysiology of several cardiovascular diseases. Nevertheless, the short half-life and rapid clearance of EXOs leads to a lack of therapeutic doses delivered to the lesioned area. Therefore, an injectable silk fibroin and alginate (SF/Alg) composite hydrogel was developed to bind folate receptor-targeted EXOs (FA-EXOs) derived from H9C2 cells for the therapy of myocardial injury following myocardial infarction-ischemia/reperfusion (MI-I/R). The resulting composite exhibits a variety of properties, including adjustable gelation kinetics, shear-thinning injectability, soft and dynamic stability that adapts to the heartbeat, and outstanding cytocompatibility. After injected into the damaged rat heart, administration of SF/Alg + FA-EXOs significantly enhanced cardiac function as demonstrated by improved ejection fraction, fractional shortening and decreased fibrosis area. The results of real-time PCR and immunofluorescence staining show a remarkable up-regulation in the expression of proteins (CD31) and genes (VWF and Serca2a) related to the heart. Conversely, expression of fibrosis-related genes (TGF-β1) decreased significantly. Therefore, the obtained SF/Alg + FA-EXOs system remarkably enhanced the intercellular interactions, promoted cell proliferation and angiogenesis, and achieved an outstanding therapeutic effect on MI.
研究领域:
生物材料学
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心血管医学
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再生医学
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DOI
PubMed
高影响因子
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