MOLECULAR BIOLOGY REPORTS
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2025
·Vol. 52
·期 1
·1-13
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IF 2.8
Wu Wanqi,Wang Jun,Wang Guanglu,Wang Feibiao,Yang Yue,Liu Zhijun,Song Qimei,Chen Si,Chen Huizhen
Background Sepsis can cause severe cardiac damage, and matrix metalloproteinase 9 (MMP9) is involved in the inflammatory response and tissue injury processes. Monotropein is a monoterpene glycoside with anti-inflammatory and antioxidant effects. This study aims to investigate whether monotropein can alleviate sepsis-induced cardiac injury by affecting the activity of MMP9. Methods and results The correlation between MMP9 and septic cardiac injury was explored using differential expression gene analysis from the GEO database and an in vitro lipopolysaccharide (LPS)-stimulated H9c2 cell model. In a cecal ligation and puncture (CLP)-induced mouse sepsis model, the effects of monotropein on myocardial cell apoptosis, inflammatory factor expression, and antioxidant enzyme levels were validated through drug administration. The results showed that MMP9 was significantly upregulated in sepsis patients. In the H9c2 cell model, LPS-induced MMP9 activity was positively correlated with cell damage. Inhibition of MMP9 alleviates LPS-induced myocardial matrix disruption and apoptosis. Monotropein exerts anti-matrix degradation and anti-apoptotic effects through MMP9 in LPS-induced H9c2 cells. Monotropein also reduced the expression of LPS-induced inflammatory factors (TNF-α, IL-1β, IL-6).In the mouse model, monotropein decreased oxidative stress damage (lower MDA levels, increased GSH, T-AOC, CAT enzyme activity), and improved cardiac injury by inhibiting myocardial cell apoptosis-related proteins (Bax, Bcl-2, and Caspase-3 activation). Conclusion Monotropein exerts a protective effect on septic cardiac injury by inhibiting MMP9 activity, reducing inflammatory response, and enhancing antioxidant capacity, thereby ameliorating myocardial cell damage and apoptosis. Graphical abstract
研究领域:
医学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2021
·
IF 5.037
Zhenjie Sun,Qian Chai,Ziying Zhang,Dexue Lu,Ziang Meng,Weihua Wu
Aims Glycemic variability has been shown to be more harmful in the development of diabetic complication than sustained chronic hyperglycemia. In this present study, we tried to reveal the effects of glycemic variability on cardiac damage in diabetic mice and investigate whether sodium-glucose cotransporter 1 (SGLT1), an important cardiac glucose transporter, functions as an important mediator in the process. Materials and methods Type 2 diabetes mellitus (DM) mice were induced by a high-fat diet and intraperitoneal injection of streptozotocin (STZ), and then glycemic variability in type 2 diabetes mellitus (GVDM) was induced by alternately injecting insulin and glucose to DM mice. In order to determine the roles of SGLT1 in GVDM mice, SGLT1 inhibition was performed using shRNA against SGLT1. The blood glucose level, the cardiac function and myocardial injury were assessed. And the expressions of SGLT1 and the activations of NLRP3/caspase-1 pathway and NF-κB in left ventricular tissues were measured. Key findings The results showed that SGLT1 was highly expressed in heart of GVDM mice compared to control and DM groups, and knockdown of SGLT1 reduced glycemic variability in GVDM mice. Moreover, glycemic variability impaired cardiac function, aggravated cardiac injury and induced NLRP3/caspase-1-mediated inflammatory response and pyroptosis. And knockdown of SGLT1 significantly attenuated the cardiac damages that induced by glycemic variability. Significance The results indicated that glycemic variability could cause cardiac damage and induce inflammatory response and pyroptosis of cardiomyocytes in diabetic mice, which could be partially blocked by SGLT1 silence.
研究领域:
内分泌学
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心脏病学
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糖尿病
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2024
·
IF 3.9
Qiao Wang,Shasha Zhang,Jiahao Ding,Zhiqiang Zhang,Xinxuan Li,Yuxin Chen,Yangye Zhu,Danping Zeng,Jingquan Dong,Yi Liu
Avermectin (AVM) is a broad-spectrum antibiotic from the macrolide class, extensively employed in fisheries and aquaculture. Nevertheless, its indiscriminate utilisation has resulted in a substantial accumulation of remnants in the aquatic ecosystem, potentially inflicting significant harm to the cardiovascular system of aquatic species. Ferulic acid (FA) is a naturally occurring compound in wheat grain husks. It possesses potent anti-inflammatory and antioxidant properties, which can help reduce cardiovascular damage. Additionally, its affordability makes it an excellent option for aquaculture usage as a feed additive. This article explored the potential of FA as a feed additive to protect against AVM-induced heart damage in carp. We subjected carp to AVM for 30 days and provided them with a diet of 400 mg/kg of FA. FA substantially reduced the pathogenic damage to heart tissue caused by AVM, as shown through hematoxylin-eosin staining. The biochemical analysis revealed that FA markedly enhanced the activity of antioxidant enzymes catalase (CAT), glutathione (GSH), and total antioxidant capacity (T-AOC) while reducing the malondialdehyde (MDA) content. Furthermore, qPCR analysis demonstrated a substantial increase in the mRNA levels of transforming growth factor-β1 ( tgf-β1 ) and interleukin-10 ( il-10 ) simultaneously, significantly reducing the expression levels of interleukin-10 ( il-6 ), interleukin-1β ( il-1β ), tumor necrosis factor-α ( tnf-α ) and inductible nitric oxide synthase ( inos ). Through the mitochondrial apoptotic route, FA reduced AVM-induced cell death in carp heart cells by upregulating bcl-2 while downregulating the mRNA expression levels of bax , fas , caspase8 and caspase9 . In summary, FA alleviated cardiac injury by inhibiting AVM-induced oxidative stress, inflammatory response, and apoptosis in carp heart tissue.
研究领域:
水产养殖学
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毒理学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2021
·
IF 3.352
Chunlin Yu,Mohan Qiu,Zengrong Zhang,Xiaoyan Song,Huarui Du,Han Peng,Qingyun Li,Li Yang,Xia Xiong,Bo Xia,Chenming Hu,Jialei Chen,Xiaosong Jiang,Chaowu Yang
As a ubiquitous heavy metal, cadmium ( Cd ) is highly toxic to various organs. However, the effects and molecular mechanism of Cd toxicity in the chicken heart remain largely unknown. The goal of our study was to investigate the cardiac injury in chickens' exposure to Cd. We detected the levels of oxidative stress–related molecules in the Cd-induced chicken heart, and assessed the histopathological changes by hematoxylin and eosin staining. RNA sequencing was performed to identify differentially expressed mRNAs between the Cd-induced group and control group. The expression of candidate genes involved in oxidative stress was certified by quantitative reverse transcription PCR. Our results showed that the expression of glutathione, peroxidase, and superoxide dismutase was significantly decreased and malondialdehyde was increased in the heart of chickens by Cd induction. The disorderly arranged cardiomyocytes, swelled and enlarged cells, partial cardiomyocyte necrosis, blurred morphological structure, and notable inflammatory cell infiltration were observed in the Cd-induced chicken heart. RNA sequencing identified 23 upregulated and 11 downregulated mRNAs in the heart tissues of the chicken in the Cd-induced group, and functional pathways indicated that they were associated with oxidative stress. Moreover, CREM, DUSP8, and ITGA11 expressions were significantly reduced, whereas LAMA1 expression was induced in heart tissue of chickens by Cd treatment. Overall, our findings revealed that oxidative stress and pathological changes in the chicken heart could be triggered by Cd. The mRNA transcriptional profiles identified differentially expressed genes in the chicken heart by Cd induction, revealing oxidative stress–related key genes and enhancing our understanding of Cd toxicity in the chicken heart.
研究领域:
毒理学
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分子生物学
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心脏病学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2023
·
IF 7.2
Huihui Wang,Baoping Xie,Shuotao Shi,Rong Zhang,Qi Liang,Zhongqiu Liu,Yuanyuan Cheng
Myocardial infarction (MI) is a common disease with high morbidity and mortality. Curdione is a sesquiterpenoid from Radix Curcumae . The current study is aimed to investigate the protective effect and mechanism of curdione on ferroptosis in MI. Isoproterenol (ISO) was used to induce MI injury in mice and H9c2 cells. Curdione was orally given to mice once daily for 7 days. Echocardiography, biochemical kits, and western blotting were performed on the markers of cardiac ferroptosis. Curdione at 50 and 100 mg/kg significantly alleviated ISO-induced myocardial injury. Curdione and ferrostatin-1 significantly attenuated ISO-induced H9c2 cell injury. Curdione effectively suppressed cardiac ferroptosis, evidenced by decreasing malondialdehyde and iron contents, and increasing glutathione (GSH) level, GSH peroxidase 4 (GPX4), and ferritin heavy chain 1 expression. Importantly, drug affinity responsive target stability, molecular docking, and surface plasmon resonance technologies elucidated the direct target Keap1 of curdione. Curdione disrupted the interaction between Keap1 and thioredoxin1 (Trx1) but enhanced the Trx1/GPX4 complex. In addition, curdione-derived protection against ISO-induced myocardial ferroptosis was blocked after overexpression of Keap1, while enhanced after Keap1 silence in H9c2 cells. These findings demonstrate that curdione inhibited ferroptosis in ISO-induced MI via regulating Keap1/Trx1/GPX4 signaling pathway.
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aquaculture Reports
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2024
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IF 3.2
Shuai Zhang,Xiaomeng Ji,Xiaohui Jin,Weiping Yan,Xuhui Xu,Zibo Dong
Pollution of aquatic environment by difenoconazole (DFZ) significantly affects survival and safety of freshwater aquaculture. Due to its anti-inflammatory and antioxidant properties, plant-derived quercetin (QUE) is often used as a dietary supplement. The main purpose of this study was to explore the protective effect of QUE on heart damage caused by exposure to pesticide DFZ and the potential mechanisms of these effects. This study found that QUE could effectively reduce the myocardial enzyme spectrum index of carp after exposure to DFZ, increase the levels of total antioxidant capacity (T-AOC), glutathione (GSH), and catalase (CAT), inhibit the content of malondialdehyde (MDA), and increase the transcription levels of superoxide dismutase ( sod ), glutathione peroxidase ( gsh-px ), and cat . By reducing the expression of keap1 , QUE increased the transcription levels of nrf2 and nqo-1 , reduced the production of reactive oxygen species (ROS) in the heart after exposure to DFZ, and restored the redox homeostasis of the heart. QUE upregulated the expression of anti-inflammatory cytokines il-10 and tgf-β1 levels, downregulated the transcription levels of pro-inflammatory factor inos, il-1β , il-6 and tnf-α , and alleviated the in vivo redox imbalance caused by exposure to DFZ, leading to myocardial interstitial inflammatory cell infiltration. The results showed that QUE inhibited the apoptosis after exposure to DFZ by affecting the expression of apoptotic factors in the mitochondrial apoptotic pathway. In summary, QUE can effectively decrease myocardial injury caused by exposure to DFZ in aquatic environment.
研究领域:
水生毒理学
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药理学
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环境科学
✓ 已验证
产品关联
DOI
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2015
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IF 6.155
Zhangjian Chen,Yun Wang,Lin Zhuo,Shi Chen,Lin Zhao,Tian Chen,Yang Li,Wenxiao Zhang,Xin Gao,Ping Li,Haifang Wang,Guang Jia
Titanium dioxide nanoparticles (TiO 2 NPs) have a broad application prospect in replace with TiO 2 used as a food additive, especially used in sweets. Understanding the interaction of TiO 2 NPs with sugar is meaningful for health promotion. We used a young animal model to study the toxicological effect of orally administrated TiO 2 NPs at doses of 0, 2, 10 and 50 mg/kg per day with or without daily consumption of 1.8 g/kg glucose for 30 days and 90 days. The results showed that oral exposure to TiO 2 NPs and TiO 2 NPs + glucose both induced liver, kidney, and heart injuries as well as changes in the count of white and red blood cells in a dose, time and gender-dependent manner. The toxicological interactions between orally-administrated TiO 2 NPs and glucose were evident, but differed among target organs. These results suggest that it is necessary to limit dietary co-exposure to TiO 2 NPs and sugar. From the Clinical Editor Nanotechnology has gained entrance in the food industry, with the presence of nanoparticles now in many food items. Despite this increasing trend, the potential toxic effects of these nanoparticles to human remain unknown. In this article, the authors studied titanium dioxide nanoparticles (TiO2 NPs), which are commonly used as food additive, together with glucose. The findings of possible adverse effects on liver, kidney, and heart might point to a rethink of using glucose and TiO2 NPs combination.
研究领域:
毒理学
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食品科学
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生物医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
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2023
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IF 4.7
Baoshi Xu,Jilei Yin,Jingchao Qiang,Jiajie Gan,Xuhui Xu,Xing Li,Zunhan Hu,Zibo Dong
As an important antibiotic, avermectin (AVM) has been widely used in China, but its unreasonable application has caused serious harm to the water environment. In view of the various pharmacological effects of quercetin (QUE), such as anti-inflammatory and antioxidant, the scientific hypothesis that “QUE may cause carp poisoning by inhibiting AVM” was proposed in this study. However, its protective effect in AVM -induced heart damage has not been reported. QUE reduced the symptoms of AVM toxicity and decreased the levels of creatine kinase , lactate dehydrogenase , and creatine kinase in the serum of carp. By histological observation, QUE was found to significantly reduce cardiac fiber swelling in carp. A DHE fluorescence probe study showed that QUE was able to inhibit AVM -induced accumulation of reactive oxygen species (ROS) in carp myocardium . We found that QUE significantly increased the intracellular antioxidant enzymes CAT, T-AOC and GSH enzyme activity and reduced intracellular MDA content. In addition, QUE significantly increased il-10 and tgf-β1 expression, and significantly down-regulated tnf-α , il-6 , il-1β and inos expression. Tunel assay showed that QUE attenuated AVM -induced apoptosis, significantly decreased the transcript levels of pro-apoptosis-related genes, and increased the expression of anti-apoptosis-related genes. We also detected the protein expression of LC3 in the AVM group and QUE + AVM group, and found that the expression of LC3 was significantly increased in both groups compared with the Control group, but after adding QUE, the expression of LC3 was significantly decreased compared with the AVM group. In addition, the transcript levels of p62 and atg5 were also detected by qPCR. QUE significantly increased the expression of p62 and decreased the expression of atg5 , suggesting that QUE could attenuate AVM -induced cardiac autophagy in carp. This study will provide preliminary evidence of the principle of QUE attenuating AVM -induced myocardial injury in carp from four aspects, including oxidative stress , inflammatory response, apoptosis and autophagy, and provide a theoretical basis for its prevention and treatment.
研究领域:
水生毒理学
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药理学
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环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Open Life Sciences
·
2024
·Vol. 19
·期 1
·
IF 1.7
Xiaokeya Yasen,Renaguli Aikebaier,Atiguli Maimaiti,Munire Mushajiang
Radiotherapy for treating breast cancer is associated with cardiac damage. This study aimed to investigate the role of the interleukin (IL)-33/soluble receptor ST2 (sST2) axis in radiation-induced cardiac injury. Expressions of IL-33 and sST2 were detected in breast cancer patients following radiotherapy, radiation-induced cardiac damaged mice model, and cardiomyocytes using quantitative real-time PCR (qRT-PCR) and immunohistochemical assay. Cardiac injury was evaluated through an ultrasound imaging system and hematoxylin & eosin staining. The transcriptional factor was assessed using dual-luciferase reporter assay and chromatin immunoprecipitation. The results indicated that IL-33 and sST2 were highly expressed in breast cancer patients, which further elevated post-6 months but reduced after 12 months of radiotherapy. Radiation induces cardiac dysfunction and elevated IL-33 and sST2 levels in a time-dependent manner. However, silencing of IL-33 decreased sST2 expression to alleviate radiation-induced cardiac dysfunction. The IL-33 could be transcriptional activated by TCF7L2 by binding to IL33 promoter sites, which mutation alleviated cardiomyocyte injury caused by radiation. Additionally, radiation treatment resulted in higher levels of TCF7L2, IL-33, and sST2 in cardiomyocytes, and TCF7L2 knockdown reduced IL-33 and sST2 expression. In conclusion, TCF7L2 transcriptional-activated IL-33 mediated sST2 to regulate radiation-induced cardiac damage, providing novel insights into radiotherapy-induced cardiac damage.
Graphical abstract
研究领域:
肿瘤学
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心脏病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2022
·Vol. 59
·期 11
·7006-7024
·
IF 5.682
Han Chengzhi,Qian Xinyi,Ren Xiaorong,Zhang Shutian,Hu Li,Li Jingyao,Huang Yijun,Huang Renhui,Ooi Kokwin,Lin Hong,Xia Chunmei
Neuroinflammation in the cardiovascular center plays a critical role in the progression of hypertensive heart disease. And microglial autophagy is involved in the regulation of neuroinflammation. Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, senses mitochondrial DNA (mtDNA) and regulates autophagy. The detailed mechanisms of central cGAS affects neuroinflammatory response in hypertensive heart disease via regulating autophagy remain unknown. Angiotensin II (Ang II, 1.5 mg·kg −1 ·12 h −1 , 2 weeks) was intraperitoneally injected to induce hypertension in mice. The cGAS-STING pathway was activated in the paraventricular nucleus (PVN) of Ang II-induced hypertensive mice. The contractile dysfunction of heart was alleviated in Ang II-induced hypertensive cGAS −/− mice. To observe the central effects of cGAS on regulating hypertensive heart disease, the RU.521 (a cGAS inhibitor) was intracisternally infused in hypertensive mice. Intracisternal infusion of the RU.521-alleviated myocardial interstitial fibrosis, cardiomyocyte hypertrophy, and the contractile dysfunction in Ang II-induced hypertensive mice. Intracisternal infusion of RU.521 attenuated the microglial activation, neuroinflammation, sympathetic/parasympathetic activity ratio, and lowered blood pressure. The autophagic flux in the PVN cells was blocked, while intracisternal infusion of RU.521 alleviated this effect in the Ang II-induced hypertensive mice. In vitro, it was found that cGAS-STING activation-induced autophagic flux blockage, while when the impaired autophagic flux was facilitated by rapamycin, an autophagy inducer, the microglial M1 polarization was decreased correspondingly. In conclusion, cGAS induces the inflammatory phenotype of microglia via impairing autophagic flux, thereby participating in neuroinflammation, which leads to sympathetic overactivation in hypertension and further caused hypertensive myocardial injury.
研究领域:
心血管疾病
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神经科学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science China-Life Sciences
·
2023
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IF 9.1
Tang Kegong,Wang Xiaona,Zhao Yu,Li Xiaobei,Jiang Zhenyu,Mei Song,Chen Mingrui,Ma Yiming,Du Xinyi,Qiao Xiangyu,Sun Na,Liu Jiaqi,Jiang Chengyu
Hypertension has become a growing public health concern worldwide. In fact, hypertension is commonly associated with increased morbidity and mortality. Currently, oligonucleotide drugs have proven to be promising therapeutic agents for various diseases. In the present study, we aimed to demonstrate that a herbal small RNA (sRNA), XKC-sRNA-h3 (B55710460, F221. I000082.B11), exhibits potent antihypertensive effects by targeting angiotensin-converting enzyme (ACE) in mice. When compared with captopril, oral administration of the sphingosine (d18:1)-XKC-sRNA-h3 bencaosome more effectively prevented angiotensin II-induced hypertensive cardiac damage and alleviated kidney injury in mice. Such findings indicated that XKC-sRNA-h3 may be a novel orally available ACE inhibitor type oligonucleotide drug for hypertension.
研究领域:
药理学
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分子生物学
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心血管研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2019
·
IF 4.328
Dandan Chen,Zhe Li,Peiqing Bao,Miao Chen,Miao Zhang,Fangrong Yan,Yitao Xu,Caoyu Ji,Xinyue Hu,Daniel Sanchis,Yubin Zhang,Junmei Ye
Background NF-E2-related factor 2 (Nrf2) is a transcription factor playing cytoprotective effects in various pathological processes including oxidative stress and cardiac hypertrophy. Despite being a potential therapeutic target to treat several cardiomyopathies, the signaling underlying Nrf2-dependent cardioprotective action remains largely uncharacterized. Aim This study aimed to explore the signaling mediating the role of Nrf2 in the development of hypertensive cardiac pathogenesis by analyzing the response to Angiotensin II (Ang II) in the presence or absence of Nrf2 expression, both in vivo and in vitro. Results Our results indicated that Nrf2 deficiency exacerbated cardiac damage triggered by Ang II infusion. Mechanistically, our study shows that Ang II-triggered hypertrophy and inflammation is exacerbated in the absence of Nrf2 expression and points to the involvement of the IL-6/STAT3 signaling pathway in this event. Indeed, our results show that IL-6 abundance triggered by Ang II is increased in the absence of Nrf2 and demonstrate the requirement of IL-6 in STAT3 activation and cardiac inflammation induced by Ang II. Conclusion Our results show that Nrf2 is important for the protection of the heart against Ang II-induced cardiac hypertrophy and inflammation by mechanisms involving the regulation of IL-6/STAT3-dependent signaling.
研究领域:
心脏病学
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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
危险品化学品经营许可证（带存储）