Stem Cell Research & Therapy
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2025
·Vol. 16
·期 1
·1-17
·
IF 7.3
Du Dongdong,Wang Ting,Sun Yaodong,Zhang Yi,Zhang Bufan,Shao Jingrong,Yang Mengxue,Huang Chuan,Zuo Shengkai,Wu Naishi
Background The poor viability and paracrine function of transplanted mesenchymal stem cells (MSCs) hamper their therapeutic efficacy in ischemic heart injury treatment. Protein arginine methyltransferases (PRMTs) mediate arginine methylation and have important functions in cellular responses. However, the role of PRMTs in MSC-based therapies for ischemic heart injury remains unclear. The aim of this study was to investigate the effect of PRMT1 on MSC function and therapeutic efficacy using a mouse myocardial infarction (MI) model.Methods We isolated, cultured, and identified mouse adipose tissue-derived mesenchymal stromal cells (ADSCs). We used Furamidine, a PRMT1 inhibitor, and adenoviral shPRMT1 to study the effects of PRMT1 inhibition on ADSC proliferation, migration, and viability. We performed RNA sequencing and biochemical experiments to elucidate the molecular mechanisms of PRMT1 in ADSCs. Finally, we infected ADSCs with adenoviral shPRMT1 and administered an intramyocardial injection after MI. Cardiac function was evaluated using echocardiography and pathological staining, and ADSCs survival rates, cardiomyocyte apoptosis, and capillary density were evaluated using immunofluorescence staining.Results We found that PRMT1 was highly expressed in ADSCs and markedly upregulated in response to H2O2 challenge. Inhibition of PRMT1 by Furamidine or adenoviral shPRMT1 promoted ADSC proliferation and migration and reduced H2O2-induced ADSCs apoptosis. Mechanistically, PRMT1 inhibition significantly increased the expression of matrix metallopeptidase (MMP)-10, placenta growth factor (PlGF) and transforming growth factor (TGF)-β2 in ADSCs through transcription factor RUNX1. Blockage of RUNX1 abolished the proliferative and migratory effects of PRMT1 inhibition in ADSCs. Compared to ADSCs infected with the adenovirus-control, PRMT1 knockdown adenovirus markedly increased the survival and retention of transplanted ADSCs in injured hearts after MI. ADSCs with PRMT1 knockdown markedly improved cardiac function and alleviated cardiac fibrosis in mice after MI by reducing cardiomyocyte apoptosis and increasing capillary density.Conclusion sPRMT1 inhibition enhances the cardioprotective effect of ADSCs against MI through RUNX1-mediated production of MMP-10/PlGF/TGF-β2. Overall, PRMT1 inhibition is a promising strategy for augmenting MSCs therapeutic efficacy in ischemic cardiomyopathy.
研究领域:
心血管医学
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分子生物学
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干细胞研究
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Jiazhuo Gong,Yuwei Qiu,Chaojie Yu,Cheng Cao,Xiuqiang Li,Jiajun Lu,Weiqing Zhao,Zhongming Zhao,Haitao Zhang,Fanglian Yao,Hong Sun,Hong Zhang,Junjie Li
Ferroptosis plays a significant role in ischemic heart disease by exacerbating myocardial injury through oxidative stress, iron metabolism disorder, and inflammation. Herein, we develop an injectable hydrogel (HSD/DFO@GMs) with antiferroptosis and antioxidant properties for cardiac repair. The hydrogel is composed of dopamine-grafted oxidized hyaluronic acid, adipic acid dihydrazide grafted hyaluronic acid, and deferoxamine loaded gelatin microsphere, connected via a dynamic Schiff base bond. This hydrogel exhibits a favorable injectability and stable mechanical properties. It effectively chelates Fe2+ and scavenges the reactive oxygen species (ROS), creating a conducive microenvironment for cardiac repair. The dynamic Schiff base bond and gelatin matrix respond to the weakly acidic and MMP-2-rich microenvironment postinjury, enabling on-demand release of DFO in the injured myocardium. In vitro experiments indicate that the hydrogel significantly inhibits the ferroptosis and oxidative stress damage in H9C2 cardiomyocytes under a hypoxia/reoxygenation microenvironment. In an in vivo ischemia–reperfusion model, the HSD/DFO@GMs hydrogel reduces oxidative stress, modulates intracellular labile iron pool levels, and promotes revascularization, ultimately improving cardiac function. Overall, the HSD/DFO@GMs hydrogel provides a new strategy to improve cardiac repair by inhibiting ferroptosis and mitigating oxidative stress damage.
研究领域:
生物材料学
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心血管医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Nan Li,Min Zhou,Ziyu Wu,Yu Chen,Yu Duan,Ziqiang Zhang,Zhuolin Wu,Xue Xia,Jian Shen,Chun Mao,Mimi Wan
Delivering energy in vivo is essential for treating mitochondrial damage-related diseases. Current methods, including natural mitochondrial transplantation and artificial energy delivery systems, lack non-destructive, external energy-free, and clinically viable potential solutions. Here, artificial mitochondrial nanorobots (AMNs) carrying high-energy phosphate bonds rebuild the in vivo energy supply system to provide energy. Using ischemic heart disease (IHD) as an energy-deficient disease model and the oral route, which has high patient compliance and facilitates long-term administration, to investigate the therapeutic efficacy of AMNs. AMNs remain stable in the gastrointestinal tract, cross the intestinal barrier via a barrier-crossing unit, and target damaged heart tissue and cardiomyocytes using a motion unit chemotactically. Intracellularly, their energy-generating unit provides high-energy phosphate bonds for ATP synthesis (duration 12 h), while synergistically reducing inflammation and restoring cell viability. At the same frequency of administration, oral AMNs (50 mg kg −1 ) match intravenous AMNs (10 mg kg −1 ) in therapeutic efficacy, offering a convenient approach to improving cardiac function. Transcriptomics confirm that 200 µg AMNs emulate 5 × 10⁶ natural mitochondria, restoring energy metabolism and structural function in damaged hearts at the genetic level. This innovative design opens a new pathway for the construction of artificial energy delivery systems in vivo.
研究领域:
生物医学工程
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分子生物学
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临床医学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2023
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IF 5.6
Wang Shuai,Bai Jie,Che Yilin,Qu Weikun,Li Jing
Background: Humans with hypertensive heart disease are more likely to experience heart failure, arrhythmia, myocardial infarction, and sudden death, and it is crucial to treat this condition. Fucoidan (FO) is a natural substance derived from marine algae that has antioxidant and immunomodulatory activities. FO has also been shown to regulate apoptosis. However, whether FO can protect against cardiac hypertrophy is unknown.Methods: We investigated the effect of FO in hypertrophic models in vivo and in vitro. C57BL/6 mice were given an oral gavage of FO (300 mg/kg/day) or PBS (internal control) the day before surgery, followed by a 14-day infusion of Ang II or saline. AC-16 cells were treated with si-USP22 for 4 h and then treated with Ang II (100 nM) for 24 h. Systolic blood pressure (SBP) was recorded, echocardiography was used to assess cardiac function, and pathological changes in heart tissues were assessed by histological staining. Apoptosis levels were detected by TUNEL assays. The mRNA level of genes was assessed by qPCR. Protein expression was detected by immunoblotting.Results: Our data showed that USP22 expression was lowered in Ang II-infused animals and cells, which could promote cardiac dysfunction and remodeling. However, treatment with FO significantly upregulated the expression of USP22 and reduced the incidence of cardiac hypertrophy, fibrosis, inflammation, and oxidative responses. Additionally, FO treatment lowered p53 expression and apoptosis while increasing Sirt 1 and Bcl-2 expression.Conclusion: By reducing the level of Ang II-induced apoptosis through the regulation of USP22/Sirt 1 expression, FO treatment might improve cardiac function. According to this study, FO might be potential targeted approach for treating heart failure.
研究领域:
心脏病学
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药理学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Nature Nanotechnology
·
2024
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IF 38.1
Wu Ziyu,Chen Lin,Guo Wenyan,Wang Jun,Ni Haiya,Liu Jianing,Jiang Wentao,Shen Jian,Mao Chun,Zhou Min,Wan Mimi
Mitochondrial transplantation is an important therapeutic strategy for restoring energy supply in patients with ischaemic heart disease (IHD); however, it is limited by the invasiveness of the transplantation method and loss of mitochondrial activity. Here we report successful mitochondrial transplantation by oral administration for IHD therapy. A nitric-oxide-releasing nanomotor is modified on the mitochondria surface to obtain nanomotorized mitochondria with chemotactic targeting ability towards damaged heart tissue due to nanomotor action. The nanomotorized mitochondria are packaged in enteric capsules to protect them from gastric acid erosion. After oral delivery the mitochondria are released in the intestine, where they are quickly absorbed by intestinal cells and secreted into the bloodstream, allowing delivery to the damaged heart tissue. The regulation of disease microenvironment by the nanomotorized mitochondria can not only achieve rapid uptake and high retention of mitochondria by damaged cardiomyocytes but also maintains high activity of the transplanted mitochondria. Furthermore, results from animal models of IHD indicate that the accumulated nanomotorized mitochondria in the damaged heart tissue can regulate cardiac metabolism at the transcriptional level, thus preventing IHD progression. This strategy has the potential to change the therapeutic strategy used to treat IHD.
研究领域:
心脏病学
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纳米技术
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药学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2020
·
IF 3.616
Xichun Qin,Yeqing Zhou,Yuzhuo Wang,Ziyao Wang,Yun Wang,Jiali Chen,Lidong Zhu,Xiaoyu Quan,Zhiwei Liu,Hao Zhang,Liqun Jiang,Hongyan Dong,Zhongming Zhang
In the treatment of heart disease, strategies for the targeted delivery of protein therapeutics to the heart by inhalation are still immature. Perfluorocarbons (PFCs) are inert chemicals with good biocompatibility , and unique physico-chemical properties that have recently led to their applications in numerous fields. In this study, we combined the advantages of protein-phospholipid complexes and PFC emulsions and then synthesized protein-loaded PFC nanoemulsions (PNEs) to test whether, after inhalation, these nanoemulsions could deliver therapeutic proteins to the heart. After preparing protein-phospholipid complexes by lyophilization, we obtained PNEs by extrusion. The particle size and surface charge of PNEs were about 140 nm and -50 mV, respectively. In vitro results showed that the PNEs had a fine particle fraction of 35% and exhibited sustained protein release. Translocation studies were done using three types of pulmonary epithelial cells, and ~7% translocation was observed in the Calu-3 cell line. Further, they were easily absorbed by cells and had therapeutic effects in culture. In vivo results showed that the PNEs successfully delivered proteins to the myocardial tissue of rats and reduced ischemic myocardial injury caused by acute myocardial infarction (AMI). This study suggests that inhalation of PNEs is a new potential strategy to deliver proteins to cardiac tissues for treating heart diseases.
研究领域:
药学
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纳米技术
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心脏病学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Zefeng Jiang,Xiaowei Wen,Qin Mao,Gang Wang,Zhuo Wang,Yu Yan,Shan Gao,Xiaoqian Sun,Miao Zhang,Jiajing Liu,Rong Zhang,Baofeng Yang
Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide, and endoplasmic reticulum stress (ERS) and mitochondrial Ca 2+ overload have been involved in apoptotic cardiomyocyte death during MI. 13-Methylpalmatine (13-Me-PLT) is a natural isoquinoline alkaloid isolated from Coptis chinensis and has not been systematically studied for their potential pharmacological effects in cardiovascular diseases. We conducted the present study to elucidate whether 13-Me-PLT modulates MI pathology in animal MI and cellular hypoxic models, employing state-of-the-art molecular techniques. The results demonstrated that 13-Me-PLT preserved post-ischemic cardiac function and alleviated cardiomyocyte apoptosis. 13-Me-PLT decreased ERS and the communication between ER and mitochondria, which serves as a protective mechanism against mitochondrial Ca 2+ overload and structural and functional injuries to mitochondria. Our data revealed mitigating mitochondrial Ca 2+ overload and apoptosis by inhibiting CHOP-mediated Ca 2+ transfer between inositol 1,4,5-trisphosphate receptor (IP 3 R) in ER and VDAC1 in mitochondria as an underlying mechanism for 13-Me-PLT action. Furthermore, 13-Me-PLT produced superior effects in alleviating cardiac dysfunction and apoptosis post-MI to diltiazem and palmatine. Collectively, our research suggests that the CHOP/IP 3 R/VDAC1 signaling pathway mediates ER-mitochondrial Ca 2+ transfer and 13-Me-PLT activates this axis to maintain cellular and organellar Ca 2+ homeostasis, protecting against ischemic myocardial injury. These findings may offer an opportunity to develop new agents for the therapy of ischemic heart disease.
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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细胞生物学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2017
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IF 2.896
Benhong Xu,Huixing Deng,Xiaojing Zhang,Jingxiong Luo,Gaoxiao Zhang,Zaijun Zhang,Yuqiang Wang,Luchen Shan
ADTM, a previously reported novel Danshensu (DSS)/tetramethylpyrazine (TMP) derivative with cardioprotective and antiplatelet aggregative effects, is a promising therapeutic candidate for ischemic heart diseases . In the present study, ADTM increased coronary blood flow and protected myocardium against ischemic injury in dogs. In addition, the relaxing effect of ADTM on rat thoracic aorta and its underlying mechanisms were examined. ADTM relaxed KCl- and phenylephrine-precontracted arotic rings in a concentration-dependent manner. The relaxation by ADTM was greater than that by DSS, TMP and the mixture of DSS and TMP. ADTM induced endothelium-independent relaxation, which couldn’t be abolished by removal of endothelium and the preincubation with inhibitors of nitric oxide synthase (L-NAME) and guanylate cyclase (ODQ). Potassium channel blockers including tetraethylammonium , BaCl 2 and glibenclamide failed to inhibit the relaxation by ADTM. In addition, cyclooxygenase (COX), muscarine receptor and β-adrenoceptor were not involved in ADTM-induced vasorelaxation. ADTM inhibited contraction induced by CaCl 2 and phenylephrine in Ca 2+ -free buffer, suggesting that ADTM inhibited both extracellular Ca 2+ influx and intracellular Ca 2+ release. Taken together, the vasorelaxation of ADTM may be possibly involved in its cardioprotection. ADTM may serve as a promising candidate for the treatment of ischemic heart diseases.
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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产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2025
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IF 3.8
Xie Baogang,Zhan Dujuan,Wu Le,Wang Lele,Lei Yongrong,Liu Meng,Liu Xiaodan,Li Suping
Congenital heart disease (CHD) poses significant clinical challenges due to limitations in early prenatal diagnosis. This study aimed to identify serum metabolic biomarkers for CHD using a combined metabolomics approach. Serum samples from 55 pregnant women carrying fetuses with confirmed CHD (CHDP group) and 49 healthy controls (ZCP group) were analyzed via non-targeted 1 HNMR metabolomics, revealing distinct metabolic profiles. Six choline pathway metabolites were further quantified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Among these, N,N-dimethylglycine (DMG) exhibited the most significant reduction in the CHDP group (1.07 ± 0.03 vs. 1.55 ± 0.04 µg/mL, p < 0.001), with an area under the ROC curve (AUROC) of 0.883 in the discovery cohort. Validation in an independent cohort (58 CHDP vs. 62 ZCP) confirmed DMG’s diagnostic potential (AUROC = 0.818). While betaine-homocysteine methyltransferase 2 (BHMT2) activity showed no intergroup differences, DMG’s consistent performance highlights its utility as a non-invasive biomarker. This study underscores the clinical value of metabonomics in prenatal CHD screening and establishes DMG as a promising diagnostic marker, potentially improving early detection and perinatal management. Graphical abstract
研究领域:
代谢组学
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儿科心脏病学
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产前诊断
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生物医学研究
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产品关联
DOI
PubMed
高影响因子
ACS Sensors
·
2024
·
IF 8.2
Fangkun Yang,Jie Cao,Xiaoxue Jia,Hailiang Zhu,Jieli Zhou,Zhaocheng Liu,Hanbin Cui,Kai Wang
Cardiovascular diseases (CVDs) pose a serious threat to human health, with atherosclerosis being a leading cause of heart disease and stroke. Elevated cysteine (Cys) levels have been closely linked to an increased risk of cardiovascular diseases, underscoring its significance in cardiovascular health. However, current detection methods for cysteine in serum and atherosclerotic plaques present challenges in sensitivity, specificity, dynamic monitoring, and invasiveness. The development of more sensitive, specific, and noninvasive assays is needed to enable accurate monitoring of cysteine levels. This study introduces the development and characterization of Cys-NPs, a sensitive and selective tool for imaging cysteine in foam cells and atherosclerotic mice. Encapsulation of the HD-probe using DSPE-PEG to obtain Cys-NPs effectively reduced interference from glutathione (GSH), leading to successful preparation and validation of Cys-NPs’s nanoscale structure. At the same time, Cys-NPs was able to use the differences in Hcy and Cys concentrations in vivo to better assess Cys levels in vivo. In vitro and in vivo studies demonstrated Cys-NPs’s effective imaging of cysteine in foam cells and atherosclerotic mice, highlighting its potential for noninvasive assessment of cysteine levels in ischemic heart disease research and clinical practice.
研究领域:
心血管疾病
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医学成像
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纳米技术
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分子生物学
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临床前研究
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2023
·
IF 5
Ning Liu,Xin Jin,Xiaoyu Wang,Yujie Wu,Rui Liu,Zheng Li
Ischemic heart disease (IHD) is a serious threat to human health due to its high incidence, high mortality and difficult treatment. Tanshinone II A (Tan II A ), a significant traditional Chinese medicine monomer that has been shown to have remarkable protective effects against IHD. However, the poor solubility and stability resulted in its low oral bioavailability. In this paper, sulfonated azocalix [4]arene (SAC4A), a deep cavitand calixarene that can bind to hydrophobic drugs, is introduced as a new synthetic material to bind to traditional Chinese medicine monomer Tan II A . Thus, a SAC4A-Tan II A supramolecular drug delivery system with hypoxia reactivity (SAC4A-Tan II A ) was constructed. The complexation of inclusion complexes was confirmed by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Moreover, in vitro drug release and cell experiments indicated that SAC4A-Tan II A had good reductive and hypoxic reaction ability. In vivo pharmacokinetic study showed that AUC (0-∞) of supramolecular drug delivery system was 2.68 times that of control group ( P < 0.01). Tissue distribution showed that the AUC (0-∞) of heart, lung and liver in SAC4A-Tan II A was 5.85 times, 3.69 times and 2.19 times of that in Tan II A , respectively ( P < 0.01). In conclusion, the supramolecular delivery system showed excellent physicochemical properties and improved oral bioavailability. It provides the basis for supramolecular delivery system in the treatment of IHD.
研究领域:
药学
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药物递送系统
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心血管疾病
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超分子化学
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 46
·7634-7642
·
IF 4.776
Dawei Fan,Chunzhu Bao,Xin Liu,Dan Wu,Yong Zhang,Huan Wang,Bin Du,Qin Wei
A unique hierarchical mesoporous SnO2 microflower was utilized for the fabrication of an immunosensor. The modified nitrogen-doped carbon quantum dots (NCQDs) improved the photoelectrochemical (PEC) activity of the SnO2, and contributed to the in situ assembly of Bi2S3 nanoparticles on the surface of the SnO2 materials. Under the stimulation of visible light and ascorbic acid as an efficient electron donor, the NCQDs and Bi2S3 co-sensitized mesoporous SnO2 microflower (SnO2/NCQDs/Bi2S3) modified ITO electrode exhibited an excellent photoelectric signal arriving at around 150 μA. Moreover, a novel label-free PEC sensor based SnO2/NCQDs/Bi2S3 composite was constructed, which enabled the ultrasensitive detection of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The photocurrents decreased linearly with the logarithm of NT-proBNP concentration in the range of 0.01–50 ng mL−1 with a detection limit of 3.7 pg mL−1 (S/N = 3). Furthermore, the novel PEC immunosensor showed perfect selectivity, good stability and reproducibility, which suggest promising applications in the sensing and clinical diagnosis of cardiac disease.
研究领域:
分析化学
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生物传感器
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心脏病学
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光电化学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）