المؤلفون: Daquan Wang, Huadong Zhao, Chao Deng, Wangrui Lei, Jun Ren, Shaofei Zhang, Wenwen Yang, Chenxi Lu, Ye Tian, Ying Chen, Yao Qiu, Lingjie Meng, Yang Yang

المصدر: Journal of Advanced Research, Vol 55, Iss , Pp 145-158 (2024)

مصطلحات موضوعية: S-nanoFe, Sepsis, Myocardial injury, Oxidative stress, Inflammatory response, AMPK, Medicine (General), R5-920, Science (General), Q1-390

الوصف: Introduction: Myocardial injury is a serious complication in sepsis with high mortality. Zero-valent iron nanoparticles (nanoFe) displayed novel roles in cecal ligation and puncture (CLP)-induced septic mouse model. Nonetheless, its high reactivity makes it difficult for long-term storage. Objectives: To overcome the obstacle and improve therapeutic efficiency, a surface passivation of nanoFe was designed using sodium sulfide. Methods: We prepared iron sulfide nanoclusters and constructed CLP mouse models. Then the effect of sulfide-modified nanoscale zero-valent iron (S-nanoFe) on the survival rate, blood routine parameters, blood biochemical parameters, cardiac function, and pathological indicators of myocardium was observed. RNA-seq was used to further explore the comprehensive protective mechanisms of S-nanoFe. Finally, the stability of S-nanoFe-1d and S-nanoFe-30 d, together with the therapeutic efficacy of sepsis between S-nanoFe and nanoFe was compared. Results: The results revealed that S-nanoFe significantly inhibited the growth of bacteria and exerted a protective role against septic myocardial injury. S-nanoFe treatment activated AMPK signaling and ameliorated several CLP-induced pathological processes including myocardial inflammation, oxidative stress, mitochondrial dysfunction. RNA-seq analysis further clarified the comprehensive myocardial protective mechanisms of S-nanoFe against septic injury. Importantly, S-nanoFe had a good stability and a comparable protective efficacy to nanoFe. Conclusions: The surface vulcanization strategy for nanoFe has a significant protective role against sepsis and septic myocardial injury. This study provides an alternative strategy for overcoming sepsis and septic myocardial injury and opens up possibilities for the development of nanoparticle in infectious diseases.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2090123223000589Test; https://doaj.org/toc/2090-1232Test

الوصول الحر: https://doaj.org/article/9c4afc913ce64399b4f03ae098f0d10fTest

المؤلفون: Ying Wang, Yuerong Xu, Wangang Guo, Yexian Fang, Lang Hu, Runze Wang, Ran Zhao, Dong Guo, Bingchao Qi, Gaotong Ren, Jun Ren, Yan Li, Mingming Zhang

المصدر: Redox Biology, Vol 58, Iss , Pp 102537- (2022)

مصطلحات موضوعية: Cardiac aging, Mitophagy, Shank3, CaMKII, Oxidative stress, Medicine (General), R5-920, Biology (General), QH301-705.5

الوصف: Compromised mitophagy and mitochondrial homeostasis are major contributors for the etiology of cardiac aging, although the precise underlying mechanisms remains elusive. Shank3, a heart-enriched protein, has recently been reported to regulate aging-related neurodegenerative diseases. This study aimed to examine the role of Shank3 in the pathogenesis of cardiac senescence and the possible mechanisms involved. Cardiac-specific conditional Shank3 knockout (Shank3CKO) mice were subjected to natural aging. Mitochondrial function and mitophagy activity were determined in vivo, in mouse hearts and in vitro, in cardiomyocytes. Here, we showed that cardiac Shank3 expression exhibited a gradual increase during the natural progression of the aging, accompanied by overtly decreased mitophagy activity and a decline in cardiac function. Ablation of Shank3 promoted mitophagy, reduced mitochondria-derived superoxide (H2O2 and O2•−) production and apoptosis, and protected against cardiac dysfunction in the aged heart. In an in vitro study, senescent cardiomyocytes treated with D-gal exhibited reduced mitophagy and significantly elevated Shank3 expression. Shank3 knock-down restored mitophagy, leading to increased mitochondrial membrane potential, decreased mitochondrial oxidative stress, and reduced apoptosis in senescent cardiomyocytes, whereas Shank3 overexpression mimicked D-gal-induced mitophagy inhibition and mitochondrial dysfunction in normally cultured cardiomyocytes. Mechanistically, the IP assay revealed that Shank3 directly binds to CaMKII, and this interaction was further increased in the aged heart. Enhanced Shank3/CaMKII binding impedes mitochondrial translocation of CaMKII, resulting in the inhibition of parkin-mediated mitophagy, which ultimately leads to mitochondrial dysfunction and cardiac damage in the aged heart. Our study identified Shank3 as a novel contributor to aging-related cardiac damage. Manipulating Shank3/CaMKII-induced mitophagy inhibition could thus be an optional strategy for therapeutic intervention in clinical aging-related cardiac dysfunctions.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2213231722003093Test; https://doaj.org/toc/2213-2317Test

الوصول الحر: https://doaj.org/article/e7702b35a3214ff0a428022040e1349dTest

المؤلفون: Hao Zhou, Shuyi Wang, Shunying Hu, Yundai Chen, Jun Ren

المصدر: Frontiers in Physiology, Vol 9 (2018)

مصطلحات موضوعية: ER–mitochondria microdomains, ischemia/reperfusion injury, mitochondrial fission, mitophagy, oxidative stress, calcium signaling, Physiology, QP1-981

الوصف: The mitochondrial and endoplasmic reticulum (ER) homeostasis is pivotal to the maintenance of an array of physiological processes. The physical contact and association between ER and mitochondria, known as the ER–mitochondria microdomains or mitochondria-associated ER membrane (MAM), temporally and spatially regulates the mitochondria/ER structure and function. More evidence suggests a role for MAMs in energy production, cellular contraction and mobility, and normal extracellular signal transmission. In pathological states, such as cardiac ischemia–reperfusion (I/R injury), this ER–mitochondria microdomains may act to participate in the cellular redox imbalance, ER stress, mitochondrial injury, energy deletion, and programmed cell death. From a therapeutic perspective, a better understanding of the cellular and molecular mechanisms of the pathogenic ER–mitochondria contact should help to identify potential therapeutic target for cardiac I/R injury and other cardiovascular diseases and also pave the road to new treatment modalities pertinent for the treatment of reperfusion damage in clinical practice. This review will mainly focus on the possible signaling pathways involved in the regulation of the ER–mitochondria contact. In particular, we will summarize the downstream signaling modalities influenced by ER–mitochondria microdomains, for example, mitochondrial fission, mitophagy, calcium balance, oxidative stress, and programmed cell death in details.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fphys.2018.00755/fullTest; https://doaj.org/toc/1664-042XTest

الوصول الحر: https://doaj.org/article/7ea2fca60bb44d86be2b5fddf5e84439Test

المؤلفون: Cheng Jiang, Ze-Ning Wang, Yu-Chen Kang, Yi Chen, Wei-Xin Lu, Hai-Jun Ren, Bo-Ru Hou

المصدر: Neural Regeneration Research, Vol 17, Iss 1, Pp 137-143 (2022)

مصطلحات موضوعية: apoptosis, colony-stimulating factor-1 receptor, inflammatory response, ischemia/reperfusion, ki20227, microglia, oxidative stress, transient middle cerebral artery occlusion, Neurology. Diseases of the nervous system, RC346-429

الوصف: The survival of microglia depends on the colony-stimulating factor-1 receptor (CSF1R) signaling pathway under physiological conditions. Ki20227 is a highly selective CSF1R inhibitor that has been shown to change the morphology of microglia. However, the effects of Ki20227 on the progression of ischemic stroke are unclear. In this study, male C57BL/6 mouse models of focal cerebral ischemic injury were established through the occlusion of the middle cerebral artery and then administered 3 mg/g Ki20227 for 3 successive days. The results revealed that the number of ionized calcium-binding adaptor molecule 1/bromodeoxyuridine double positive cells in the infarct tissue was reduced, the degree of edema was increased, neurological deficits were aggravated, infarct volume was increased, and the number of peri-infarct Nissl bodies was reduced. The number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells in the peri-infarct tissue was increased. The expression levels of Bax and Cleaved caspase-3 were up-regulated. Bcl-2 expression was downregulated. The expression levels of inflammatory factors and oxidative stress-associated factors were increased. These findings suggested that Ki20227 blocked microglial proliferation and aggravated the pathological progression of ischemia/reperfusion injury in a transient middle cerebral artery occlusion model. This study was approved by the Animal Ethics Committee of Lanzhou University Second Hospital (approval No. D2020-68) on March 6, 2020.

العلاقة: http://www.nrronline.org/article.asp?issn=1673-5374;year=2022;volume=17;issue=1;spage=137;epage=143;aulast=JiangTest; https://doaj.org/toc/1673-5374Test; https://doaj.org/article/6b6b1c84253b48d6a42b6e7296ca9c3dTest

الإتاحة: https://doi.org/10.4103/1673-5374.314318Test
https://doaj.org/article/6b6b1c84253b48d6a42b6e7296ca9c3dTest

المؤلفون: Shi-Yu Lin, Dan Xu, Xia-Xia Du, Chong-Lin Ran, Lu Xu, Shao-Jun Ren, Zi-Ting Tang, Li-Zi Yin, Chang-Liang He, Zhi-Xiang Yuan, Hua-Lin Fu, Xiao-Ling Zhao, Gang Shu

المصدر: International Journal of Molecular Sciences, Vol 20, Iss 13, p 3187 (2019)

مصطلحات موضوعية: Salidroside, CCl 4, liver injury, mitochondria, oxidative stress, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: The antioxidant effect of salidroside has been proven, but its role in liver injury is poorly understood. In this study, we aimed to evaluate the protective effects and mechanism of salidroside on liver injury induced by carbon tetrachloride (CCl 4 ) in vivo. Mice were pretreated with salidroside (60 mg/kg, intraperitoneally injected, i.p.) once per day for 14 consecutive days and then administered with CCl 4 (15.95 g/kg, i.p.) for 24 h to produce a liver injury model. Salidroside attenuated hepatic transaminase elevation in serum and ameliorated liver steatosis and necrosis, thereby suggesting its protective effect on the liver. Salidroside antagonized CCl 4 -induced toxicity by equilibrating antioxidation system, thereby inhibiting reactive oxygen species accumulation, and restoring mitochondrial structure and function. Salidroside exerts antioxidant and liver-protective effects by selectively inhibiting the activation of genes, including growth arrest and DNA -damage-inducible 45 α (Gadd45a), mitogen-activated protein kinase 7 (Mapk7), and related RAS viral oncogene homolog 2 (Rras2), which induce oxidative stress in the mitogen-activated protein kinase pathway. These results revealed that salidroside can protect the liver from CCl 4 -induced injury by resisting oxidative stress and protecting mitochondrial function.

العلاقة: https://www.mdpi.com/1422-0067/20/13/3187Test; https://doaj.org/toc/1422-0067Test; https://doaj.org/article/2c5893d62c764aedad416f44b41864d3Test

الإتاحة: https://doi.org/10.3390/ijms20133187Test
https://doaj.org/article/2c5893d62c764aedad416f44b41864d3Test

المؤلفون: Li, Gang-Min¹ (AUTHOR), Chen, Jun-Ren¹ (AUTHOR), Zhang, Hui-Qiong¹ (AUTHOR), Cao, Xiao-Yu¹ (AUTHOR), Sun, Chen¹ (AUTHOR), Peng, Fu^1,2 (AUTHOR), Yin, Yan-Peng¹ (AUTHOR), Lin, Ziwei¹ (AUTHOR), Yu, Lei¹ (AUTHOR), Chen, Yan¹ (AUTHOR), Tang, Yun-Li^1,3 (AUTHOR), Xie, Xiao-Fang¹ (AUTHOR), Peng, Cheng¹ (AUTHOR)

المصدر: Evidence-based Complementary & Alternative Medicine (eCAM). 8/18/2021, p1-18. 18p. 2 Diagrams, 4 Charts.

مصطلحات موضوعية: *MITOCHONDRIAL physiology, *QUINONE, *BIOAVAILABILITY, *OXIDATIVE stress, *CELLULAR signal transduction, *DNA-binding proteins, *MITOGEN-activated protein kinases, *MOLECULAR structure, *PATIENT safety

مستخلص: Rhein, belonging to anthraquinone compounds, is one of the main active components of rhubarb and Polygonum multiflorum. Rhein has a variety of pharmacological effects, such as cardiocerebral protective effect, hepatoprotective effect, nephroprotective effect, anti-inflammation effect, antitumor effect, antidiabetic effect, and others. The mechanism is interrelated and complex, referring to NF-κB, PI3K/Akt/MAPK, p53, mitochondrial-mediated signaling pathway, oxidative stress signaling pathway, and so on. However, to some extent, its clinical application is limited by its poor water solubility and low bioavailability. Even more, rhein has potential liver and kidney toxicity. Therefore, in this paper, the pharmacological effects of rhein and its mechanism, pharmacokinetics, and safety studies were reviewed, in order to provide reference for the development and application of rhein. [ABSTRACT FROM AUTHOR]

المؤلفون: LI YAN, RUI HU, SONG TU, WEN-JUN CHENG, QIONG ZHENG, JUN-WEN WANG, WU-SHENG KAN, YI-JUN REN

المصدر: Oncology Letters; Sep2016, Vol. 12 Issue 3, p1981-1985, 5p

مصطلحات موضوعية: EMODIN, OXIDATIVE stress, CISPLATIN, OSTEOSARCOMA, REACTIVE oxygen species, CELL proliferation, LUCIFERASES

مستخلص: Previously, the application of cisplatin in chemotherapy was limited due to the significant side effects on normal cell growth. In the present study, the concomitant application of emodin with cisplatin was demonstrated to ameliorate cisplatin-induced oxidative stress and markedly suppress tumor cell proliferation for the first time. Human osteosarcoma MG-63 cells were treated with cisplatin alone or in combination with emodin. The cell viability was determined by MTS assays and the augmentation of reactive oxygen species were determined by fluorogenic probes; in addition, a stable MG-63 subline bearing antioxidant response element (ARE)-driven luciferase expression was developed to monitor the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-ARE signaling pathway. The results indicated that cisplatin or emodin may inhibit MG-63 cell proliferation in a time-or dose-dependent manner, respectively. Concomitant treatment with cisplatin and emodin demonstrated synergic anti-tumor effects. Cisplatin augmented reactive oxygen species in the MG-63 cells, followed by the translocation of Nrf2 from the cytoplasm into the nucleus, which triggered ARE-driven luciferase expression. The addition of emodin diminished the previously described phenomenon, resulting in decreased ROS augmentation, translocation of Nrf2 and ARE-driven luciferase activity. In conclusion, emodin could ameliorate cisplatin-induced oxidative stress and protect the cells from oxidative stress-induced damage. The findings of the present study provide a novel strategy for the treatment of osteosarcoma using emodin and cisplatin. [ABSTRACT FROM AUTHOR]

: Copyright of Oncology Letters is the property of Spandidos Publications UK Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Dongjuan Wang, Peng Luo, Yabin Wang, Weijie Li, Chen Wang, Dongdong Sun, Rongqing Zhang, Tao Su, Xiaowei Ma, Chao Zeng, Haichang Wang, Jun Ren, Feng Cao

المصدر: Diabetes; May2013, Vol. 62 Issue 5, p1697-1708, 12p, 5 Color Photographs, 2 Black and White Photographs, 2 Charts

مصطلحات موضوعية: DIABETES complications, GLUCAGON-like peptides, STREPTOZOTOCIN, LABORATORY rats, REACTIVE oxygen species, OXIDATIVE stress

مستخلص: Impaired cardiac microvascular function contributes to cardiovascular complications in diabetes. Glucagon-like peptide-1 (GLP-1) exhibits potential cardioprotective properties in addition to its glucose-lowering effect. This study was designed to evaluate the impact of GLP-1 on cardiac microvascular injury in diabetes and the underlying mechanism involved. Experimental diabetes was induced using streptozotocin in rats. Cohorts of diabetic rats received a 12-week treatment of vildagliptin (dipeptidyl peptidase-4 inhibitor) or exenatide (GLP-1 analog). Experimental diabetes attenuated cardiac function, glucose uptake, and microvascular barrier function, which were significantly improved by vildagliptin or exenatide treatment. Cardiac microvascular endothelial cells (CMECs) were isolated and cultured in normal or high glucose medium with or without GLP-1. GLP-1 decreased high-glucose-induced reactive oxygen species production and apoptotic index, as well as the levels of NADPH oxidase such as p47^phox and gp91^phox. Furthermore, cAMP/PKA (cAMP-dependent protein kinase activity) was increased and Rho-expression was decreased in high-glucose-induced CMECs after GLP-1 treatment. In conclusion, GLP-1 could protect the cardiac microvessels against oxidative stress, apoptosis, and the resultant microvascular barrier dysfunction in diabetes, which may contribute to the improvement of cardiac function and cardiac glucose metabolism in diabetes. The protective effects of GLP-1 are dependent on downstream inhibition of Rho through a cAMP/PKA-mediated pathway. [ABSTRACT FROM AUTHOR]

: Copyright of Diabetes is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Kandadi, Machender R., Xuejun Yu, Frankel, Arthur E., Jun Ren

المصدر: BMC Medicine; 2012, Vol. 10 Issue 1, p134-149, 16p, 8 Graphs

مصطلحات موضوعية: HEART diseases, CATALASE, OXIDATIVE stress, TOXINS, AUTOPHAGY

مستخلص: Background: Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods: Wild type (WT) and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.)). Cardiomyocyte contractile and intracellular Ca²⁺ properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspaselike activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Results: Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca²⁺ handling), the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Conclusions: Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca²⁺ anomalies, possibly through regulation of autophagy and mitochondrial function. [ABSTRACT FROM AUTHOR]

: Copyright of BMC Medicine is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Shan Wu, Qun Li, Min Du, Shi-Yan Li, Jun Ren

المصدر: Clinical & Experimental Pharmacology & Physiology; Jan/Feb2007, Vol. 34 Issue 1/2, p81-87, 7p, 2 Black and White Photographs, 3 Charts, 3 Graphs

مصطلحات موضوعية: OXIDATIVE stress, AGING, CATALASE, MUSCLE cells, PROTEOMICS, TRANSGENIC mice, EXPERIMENTAL physiology

مستخلص: 1. Oxidative stress plays a role in senescence-associated organ deterioration. This is supported by the beneficial effects of anti-oxidants against ageing-related organ damage, although their role in cardiac ageing has not been elucidated. 2. The aim of the present study was to examine the impact of cardiac-specific overexpression of catalase, an enzyme for H2O2 detoxification, on cardiac contractile function and protein damage in young (3–4 months) and old (26–28 months) male mice. Lifespan was analysed using the Kaplan–Meier survival curve. Cardiomyocyte contractile indices at various stimulus frequencies (0.1–5.0 Hz) were analysed, including peak shortening (PS), time to 90% PS, time to 90% relengthening (TR90) and maximal velocity of shortening/relengthening (±dL/dt). Protein damage was assessed using protein carbonyl formation. Catalase transgenic mice showed longer lifespan than wild-type FVB mice. The catalase transgene itself did not alter bodyweight or organ weight, or myocyte function. Ageing depressed ±dL/dt and prolonged TR90, but had no effect on other indices in FVB mice. Increased frequency triggered decreases in PS amplitude were exaggerated in aged FVB myocytes. Interestingly, ageing-induced mechanical defects were significantly attenuated in myocytes from catalase mice. Protein carbonyl formation was elevated in aged FVB compared with young FVB mice, which was significantly diminished in catalase mice. The proteomes of the myocardium of young or old FVB and catalase mice were compared using two-dimensional gel electrophoresis and mass spectrometry. Six proteins with differential expression between yound and old FVB groups were tentatively identified, some of which were reversed by catalase. 3. In summary, the present data suggest that catalase protects cardiomyocytes from ageing-induced contractile defects and protein damage. [ABSTRACT FROM AUTHOR]

: Copyright of Clinical & Experimental Pharmacology & Physiology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)