Foods
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2023
·Vol. 12
·期 13
·2471
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IF 5.2
Jinjie Li,Yi Li,Xiangying Suo,Jiangtao Li,Da Huang,Guangning Kou
Bayberry is known to be a rich source of natural flavonoids and has been reported to have various health-promoting abilities. However, its function on regulating skeletal muscle fiber type remains unclear. This study examined whether bayberry extract affects skeletal muscle fiber type by promoting fast myofiber formation, as well as the potential molecular mechanism. After eight weeks, the “Biqi” bayberry extract (BBE) groups mice displayed markedly enhanced grip strength and improved metabolic rate compared to the control group mice. BBE also significantly increased myofibers size, LDH activity, MyHC-IIb (fast-twitch mRNA) expression, and the percentage of fast-twitch myofibers, while decreasing SDH activity, MyHC-I (slow-twitch mRNA) expression, and slow-twitch myofibers percentage in the skeletal muscle of the mice. The effect of BBE on regulating skeletal muscle fiber type remodeling is likely attributed to its activation of the Akt-FoxO1 pathway. Our findings indicated that BBE can effectively regulate the expression and proportion of fast-twitch fibers, making it a potential therapy for improving glucose homeostasis of skeletal muscle.Keywords:bayberry extract;skeletal muscle;fast-twitch fibers;myofiber type;FoxO1
研究领域:
药理学
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分子生物学
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运动生理学
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PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2025
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IF 14.6
Xuewen Yang,Yanwei Zhang,Xiaoping Leng,Yanying Wang,Manyu Gong,Dongping Liu,Haodong Li,Zhiyuan Du,Zhuo Wang,Lina Xuan,Ting Zhang,Han Sun,Xiyang Zhang,Jie Liu,Tong Liu,Tiantian Gong,Zhengyang Li,Shengqi Liang,Lihua Sun,Lei Jiao,Baofeng Yang,Ying Zhang
Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.
研究领域:
心脏病学
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分子生物学
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病理学
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药理学
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DOI
PubMed
高影响因子
Analytical Methods
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2024
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IF 2.7
Luhai Wang,Jiaze Sun,Siwei Dai,Pengfei Zhang,Yefei Zhu,Yu Zhang
Myocardial fibrosis is a pathological condition characterized by the excessive accumulation of extracellular matrix proteins, primarily collagen, within the myocardium. Early symptoms of myocardial fibrosis are often subtle, leading to late detection. As the disease progresses, it is often associated with life-threatening complications. Therefore, myocardial fibrosis urgently demands a diagnostic system that is rapid, effective, and preferably non-invasive. In this study, we developed a highly sensitive microfluidic light-initiated chemiluminescent assay (LICA) for the simultaneous detection of cTnI, NT-proBNP, HA, LN, PICP, and PIIINP, the key biomarkers involved in the occurrence and development of myocardial fibrosis. The system is highly integrated and compact, incorporating reagent lyophilization and whole blood separation technologies, and is suitable for point-of-care testing. By combining advantages of centrifugal microfluidics and LICA, the system effectively shortens the detection time for key biomarkers associated with MACEs. Moreover, the system provides optimal analytical performance, with LoDs of 0.0018 ng mL−1, 0.0127 ng mL−1, 3.52 ng mL−1, 6.88 ng mL−1, 4.68 ng mL−1, and 0.072 ng mL−1 for cTnI, NT-proBNP, HA, LN, PIIINP and PICP, respectively. Ultimately, the system can achieve an AUC of 0.548, 0.670, 0.772, 0.752, 0.833 and 0.713 for cTnI, NT-proBNP, HA, LN, PIIINP, and PICP, respectively, and an overall combined ROC of 0.946 for the detection of myocardial fibrosis, indicating its excellent efficacy and potential for widespread clinical applications.
研究领域:
医学诊断
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生物工程
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心血管病学
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DOI
PubMed
高影响因子
Heliyon
·
2023
·
IF 4
Nanyu Cao,Heyang Wang
Regular insulin therapy is significantly related to worse cardiovascular outcomes in patients with type 2 diabetes and heart failure. However, the mechanisms of the causal relationship remain unclear. In this study, we observed the effect of insulin on cardiac structure and function and found that insulin dramatically augmented angiotensin II (Ang II)-induced cardiac dysfunction, as well as the proliferation and collagen production of primary cardiac fibroblasts. Total STAT3 expression, but not activation was stimulated by insulin; the effect of insulin on Ang II-induced fibrosis disappeared when STAT3 was blocked and could be entirely suppressed by the MEK inhibitor PD0325901. Our findings suggest a noninsulin-dependent glucose-lowering regimen for patients with type 2 diabetes (T2DM) and heart failure (HF).
研究领域:
心血管病学
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内分泌学
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分子生物学
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DOI
高影响因子
Acta Pharmaceutica Sinica B
·
2025
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IF 14.6
Jingyu Wang,Xiangning Liu,Rongxin Zhu,Ying Sun,Boyang Jiao,Keyan Wang,Yong Jiang,Yong Wang,Chun Li,Wei Wang
Myocardial fibrosis (MF) is a common pathological hallmark of cardiovascular diseases, reflecting shared mechanisms in their progression. However, the lack of reliable MF models that accurately mimic its pathogenesis has hindered drug discovery, highlighting the urgent need for more effective therapeutic agents. Herein, a novel contractile three-dimensional (3D) myocardial tissue model integrating cardiomyocytes, cardiac-fibroblasts, and bone marrow-derived macrophages in collagen hydrogel was developed to simulate the fibrotic changes of cardiovascular disease, and facilitate the screening of anti-MF compounds. The 3D myocardial tissue model exhibited precise, visualizable, and quantifiable contractile characteristics under hypoxia and drug interventions. 76 compounds extracted from the resins of Toxicodendron vernicifluum , a traditional Chinese medicine with clear clinical benefits for fibrotic diseases, were screened for anti-fibrotic activity. Using an in vitro 3D oxygen–glucose deprivation (OGD)-treated myocardial tissue model instead of a two-dimensional transforming growth factor- β treated cardiac-fibroblasts model, two candidates including LQ-40 and SQ-3 exert impressive anti-MF activity, which was further validated in left anterior descending coronary artery ligation-induced MF mouse model. The current results demonstrate the feasibility and advantage of the novel contractile 3D tissue model with multi-cell types in discovering candidates for MF, further stressing the great potential of regulating macrophages in the treatment of MF.
研究领域:
心血管病学
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药理学
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生物医学工程
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DOI
PubMed
高影响因子
Aquaculture Reports
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2024
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IF 3.2
Yu-Long Gong,Xiao-Hong Lai,Yao Xiao,Peng Jiang,Yu-Feng Song
To elevate the effects of creatine on muscle growth, flesh quality, lipid metabolism and antioxidant responses of aquatic animals, we set up three diets with dietary creatine levels at 0 % (Control), 1 % and 2 % for juvenile grass carp (4.33 ± 0.02 g). Experimental fish were stocked in nine 300-L tanks (30 fish/tank) and randomly assigned with one of the three diets for 8 weeks. We found that 2 % dietary creatine improved the growth performance (SGR) and feed utilization (FCR) of the experimental grass carp. Dietary creatine supplementation further increased the diameter of muscle fibers through elevating the expression levels of muscle growth-related genes ( pax3 , mrf4, myog , myf5 , mef2a , and mef2d ) and proteins (Pax3, Myog and Mef2a). Furthermore, both 1 % and 2 % creatine supplementation elevated the muscle flesh quality of grass carp, indicated by the enhanced water holding capacity, improved texture properties, increased flavor compounds (flavor nucleotides and amino acids) content and decreased odorants compounds (2-MIB and GSM) content in the muscle. Dietary creatine supplementation also reduced muscle lipid deposition main forced by suppressing lipogenesis and activating fatty acids β-oxidation. Moreover, the increased antioxidant capability and reduced oxidative stress were found in the muscle of creatine supplementation groups, as evaluated by Nrf2 nuclear-translocation, enzymatic activities, antioxidative genes and proteins expression. Therefore, our study suggested that 1 % or 2 % dietary creatine levels not only promoted the muscle growth, but also enhanced the flesh quality of juvenile grass carp.
研究领域:
水产养殖学
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营养学
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分子生物学
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DOI
高影响因子
Chinese Medicine
·
2024
·
IF 5.3
MingShan Zhang,YuFei Zhang,JingGang He,XinRui Wang,YinYin Wang,LinYan Li,Ling Tao,Min Zhang,Xiangchun Shen
Background Diabetic cardiomyopathy (DCM), characterized by myocardial fibrosis, is a major cause of mortality and morbidity in diabetic patients; the inhibition of cardiac fibrosis is a fundamental strategy for treating DCM. Gastrodin (GAS), a compound extracted from Gastrodia elata protects against DCM, but the molecular mechanism underlying its antifibrotic effect has not been elucidated. Methods In vivo, the effects of GAS were investigated using C57BL/6 mice with DCM, which was induced by administering a high-sugar, high-fat (HSF) diet and streptozotocin (STZ). We assessed the cardiac function in these mice and detected histopathological changes in their hearts and the degree of cardiac fibrosis. In vitro, neonatal rat cardiac fibroblasts (CFs) were transformed into myofibroblasts by exposing them to high glucose combined with high palmitic acid (HG-PA), and CFs were induced by pEX-1 (pGCMV/MCS/EGFP/Neo) plasmid-mediated overexpression of KLK8, which contains the rat KLK8 gene. The KLK8 siRNA was knocked down to study the effects of GAS on CF differentiation, collagen synthesis, and cell migration by specific mechanisms of action of GAS. Results GAS attenuated pathological changes in the hearts of DCM mice, rescued impaired cardiac function, and attenuated cardiac fibrosis. Additionally, the results of molecular docking analysis showed that GAS binds to kinin-releasing enzyme-related peptidase 8 (KLK8) to inhibit the increase in protease-activated receptor-1 (PAR-1), thus attenuating myocardial fibrosis. Specifically, GAS attenuated the transformation of neonatal rat CFs to myofibroblasts exposed to HG-PA. Overexpressing KLK8 promoted CF differentiation, collagen synthesis, and cell migration, and KLK8 siRNA attenuated HG-PA-induced CF differentiation, collagen synthesis, and cell migration. Further studies revealed that a PAR-1 antagonist, but not a PAR-2 antagonist, could attenuate CF differentiation, collagen synthesis, and cell migration. Additionally, GAS inhibited KLK8 upregulation and PAR1 activation, thus blocking the differentiation, collagen synthesis, and cell migration of HG-PA-exposed CFs and triggering TGF-β1/Smad3 signaling. Conclusion GAS alleviated pathological changes in the hearts of DCM model mice induced by an HSF diet combined with STZ. KLK8 mediated HG-PA-induced differentiation, collagen synthesis, and the migration of CFs. GAS attenuated the differentiation, collagen synthesis, and migration of CFs by inhibiting the KLK8-PAR1 signaling axis, a process in which TGF-β1 and Smad3 are involved. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1186/s13020-024-01035-4.
研究领域:
医学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Scientific Reports
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2025
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IF 3.9
Xu Qiuling,Liu Zhuoxi,Wang Liyuan,Liu Guoyang,Zhao Long,Yue Hui,Liu Yong
Diabetic cardiomyopathy (DCM) requires a systematic approach for effective management. Focusing on key signaling pathways in myocardial fibrosis could offer novel therapeutic approaches for DCM. The objective of this research is to investigate new biomarker and the underlying mechanisms by which baicalin intervenes in the progression of DCM. Swiss Target Prediction databases and weighted correlation network analysis (WGCNA) were employed to collect and analyze targets of baicalin and DCM. Intersection targets were obtained through venn online website, network visualization was conducted through STRING database and Cytoscape 3.7.2 software. Molecular docking validation was completed via AutoDock Vina software. Western blotting, RT-qPCR and histology were carried out to validate the direct targets of baicalin and explore the molecular mechanism during DCM progression. In mice induced to DCM, we observed that disruptor of telomeric silencing 1-like (DOT1L) was upregulated. Baicalin (BC) reduced myocardial fibrosis in mice as indicated by the reduced expression levels of fibrosis markers COL-1 and TGF-β. The inhibitory effect of BC was reversed by overexpressed DOT1L and further enhanced by silenced DOT1L. Our results indicate that cardiomyocyte DOT1L exerts a pathogenic role in DCM and BC specifically targets DOT1L/COL-1 signaling to reduce myocardial fibrosis in DCM.
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2025
·
IF 2.2
Xiaoyun Yang,Yi Wang,Yujin Feng,Feng Wang,Lijuan Gao,Yueheng Wang
Myocardial infarction is often accompanied by symptoms of myocardial fibrosis, causing myocardial systolic and diastolic dysfunction. High levels of TMAO are considered to be strongly connected to cardiovascular diseases occurrence. The objective of this investigation was to determine whether formal TMAO affects the development of cardiac muscle fibers. The left anterior descending (LAD) coronary artery was ligated to construct myocardial infarction mouse model, while the control group mouse was only operated vessel separation. According to whether or not TMAO intervention is given, mice were divided into control, TMAO, myocardial infarction model(model), and myocardial infarction model + TMAO(model + TMAO). TMAO and model + TMAO group received 0.24 % TMAO in drinking water for one month. After modeling, echocardiography assessed cardiac function, and cardiac tissues were collected for analysis. Masson staining observed collagen deposition, while immunohistochemistry was conducted to identify fibronectin, collagen III, collagen I, and JAK/STAT pathway related proteins levels. In vitro, mouse cardiac fibroblasts were cultured and treated with varying TMAO concentrations (0, 300, 600, 900 μM), and Western blot was carried out to analyse changes in fibronectin, collagen III, and collagen I. Subsequently, the JAK2/STAT3 pathway inhibitor AG490 was utilized to treat cells and further examine the changes of fibronectin and collagen. The in vivo data showed TMAO significantly increases fibrosis and upregulates fibronectin, collagen III, and collagen I. In vitro experiments indicated that TMAO promotes fibronectin, collagen III, and collagen I levels through regulating the JAK2/STAT3 pathway, ultimately accelerating fibrosis.
研究领域:
心血管疾病研究
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分子生物学
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产品关联
DOI
PubMed
高影响因子
DIABETES RESEARCH AND CLINICAL PRACTICE
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2025
·
IF 7.4
Mei He,Weiguang Luo,Shuwei Ning,Yuexin Yu,Bin Yang,Zhikun Guo
Objective Beta-hydroxybutyrate (BHB) has been demonstrated to enhance cardiac function in patients with diabetic cardiomyopathy (DCM), the underlying mechanism remains unclear. Methods A DCM rat model was established, BHB was administered via intraperitoneal injection. The therapeutic effects of BHB were assessed based on cardiac function, fasting glucose levels, myocardial fibrosis markers and myocardial macrophage polarization. To elucidate the mechanism of action, co-culture experiments were conducted using cardiac fibroblasts and peritoneal macrophages to evaluate collagen expression in fibroblasts and macrophage polarization under BHB treatment. Results BHB improved cardiac function in DCM rats, reduced fasting glucose levels, alleviated cardiac fibrosis and modulated macrophage polarization. After BHB treatment, the proportion of M1 macrophages decreased while that of M2 macrophages increased in the myocardium of DCM rats. Cardiac fibroblasts isolated from neonatal rats, when co-cultured with peritoneal macrophages under high-glucose conditions, exhibited altered macrophage polarization and collagen expression. High-glucose conditions promoted an increase in M1 macrophages and a decrease in M2 macrophages. BHB treatment reversed this trend by reducing M1 macrophages and promoting M2 macrophage polarization. Conclusions We show that BHB mitigates cardiac fibrosis in DCM rats by promoting M2 macrophage polarization. BHB may be a useful therapeutic approach for DCM treatment.
研究领域:
心脏病学
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内分泌学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2021
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IF 13.273
Chao Wu,Xiaokang Na,Wuchao Ma,Chao Ren,Qixin Zhong,Tao Wang,Ming Du
High internal phase emulsions (HIPEs) are versatile platforms for various applications owing to the low-density, interconnected structure, and large specific area. The mechanical properties of existing HIPEs, especially those stabilized solely by one naturally-occurring substance, hinder their practical applications. In this study, we disclose strong (up to 1.6 MPa), tough (up to 0.7 MJ m −3 ), and fatigue-resistant HIPEs stabilized solely by cod myofibers (CMs). Unlike conventional Pickering-type HIPEs, intrinsic strengthening and toughening of CMs, resultant from cadmium bridging of actin and myosin, endow the superior mechanical properties of our HIPEs. The HIPEs are conformable to 3D printing, yielding architectures with tailorable rheological properties that are vital for texture of foods. Besides, the network structures of our HIPEs serve the template of aerogels that had the oil absorption capacity of up to 58 g g −1 and maintained properties after repeated uses. The ability of aerogels to absorb petroleum or soy oil spilled on down feathers within 40 s shows the potential applications in fabric cleansing and remediation of oil spillage including rescuing seabirds. Furthermore, the porous structures of aerogels are excellent platforms for osteoblast attachment and proliferation and therefore are potential scaffolds in tissue engineering. The mechanically robust, reusable, and biofriendly HIPEs in this study can be developed as facile and reusable materials for numerous multidisciplinary applications.
研究领域:
食品科学
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材料科学
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环境科学
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生物医学工程
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DOI
高影响因子
Antioxidants
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2023
·Vol. 12
·期 3
·679
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IF 7
Tong Zhu,Jingjing Song,Bin Gao,Junjie Zhang,Yabei Li,Zhaoyang Ye,Yuxiang Zhao,Xiaogang Guo,Feng Xu,Fei Li
Myocardial fibrosis progression and imbalanced redox state are closely associated with increased extracellular matrix (ECM) stiffness. Candesartan (CAN), an angiotensin II (Ang II) receptor inhibitor, has shown promising anti-fibrosis and antioxidant efficacy in previous cardiovascular disease studies. However, the effect of ECM stiffness on CAN efficacy remains elusive. In this study, we constructed rat models with three different degrees of myocardial fibrosis and treated them with CAN, and then characterized the stiffness, cardiac function, and NADPH oxidase-2 (NOX2) expression of the myocardial tissues. Based on the obtained stiffness of myocardial tissues, we used polyacrylamide (PA) gels with three different stiffness to mimic the ECM stiffness of cardiac fibroblasts (CFs) at the early, middle, and late stages of myocardial fibrosis as the cell culture substrates and then constructed CFs mechanical microenvironment models. We studied the effects of PA gel stiffness on the migration, proliferation, and activation of CFs without and with CAN treatment, and characterized the reactive oxygen species (ROS) and glutathione (GSH) levels of CFs using fluorometry and scanning electrochemical microscopy (SECM). We found that CAN has the best amelioration efficacy in the cardiac function and NOX2 levels in rats with medium-stiffness myocardial tissue, and the most obvious anti-fibrosis and antioxidant efficacy in CFs on the medium-stiffness PA gels. Our work proves the effect of ECM stiffness on CAN efficacy in myocardial anti-fibrosis and antioxidants for the first time, and the results demonstrate that the effect of ECM stiffness on drug efficacy should also be considered in the treatment of cardiovascular diseases.Keywords:myocardial fibrosis;candesartan (CAN);extracellular matrix (ECM);oxidative stress;scanning electrochemical microscopy (SECM)
研究领域:
心脏病学
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药理学
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生物医学工程
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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）