Doxorubicin (DOX) is an anthracycline chemotherapy drug used in the treatment of various types of cancer. However, short-term and long-term cardiotoxicity limits the clinical application of DOX. ...Currently, dexrazoxane is the only approved treatment by the United States Food and Drug Administration to prevent DOX-induced cardiotoxicity. However, a recent study found that pre-treatment with dexrazoxane could not fully improve myocardial toxicity of DOX. Therefore, further targeted cardioprotective prophylaxis and treatment strategies are an urgent requirement for cancer patients receiving DOX treatment to reduce the occurrence of cardiotoxicity. Accumulating evidence manifested that Sirtuin 1 (SIRT1) could play a crucially protective role in heart diseases. Recently, numerous studies have concentrated on the role of SIRT1 in DOX-induced cardiotoxicity, which might be related to the activity and deacetylation of SIRT1 downstream targets. Therefore, the aim of this review was to summarize the recent advances related to the protective effects, mechanisms, and deficiencies in clinical application of SIRT1 in DOX-induced cardiotoxicity. Also, the pharmaceutical preparations that activate SIRT1 and affect DOX-induced cardiotoxicity have been listed in this review.
Although it is known that the expression and activity of sirtuin 1 (SIRT1) significantly decrease in doxorubicin (DOX)-induced cardiomyopathy, the role of interaction between SIRT1 and sestrin 2 ...(SESN2) is largely unknown. In this study, we investigated whether SESN2 could be a crucial target of SIRT1 and the effect of their regulatory interaction and mechanism on DOX-induced cardiac injury. Here, using DOX-treated cardiomyocytes and cardiac-specific Sirt1 knockout mice models, we found SIRT1 deficiency aggravated DOX-induced cardiac structural abnormalities and dysfunction, whereas the activation of SIRT1 by resveratrol (RES) treatment or SIRT1 overexpression possessed cardiac protective effects. Further studies indicated that SIRT1 exerted these beneficial effects by markedly attenuating DOX-induced oxidative damage and apoptosis in a SESN2-dependent manner. Knockdown of Sesn2 impaired RES/SIRT1-mediated protective effects, while upregulation of SESN2 efficiently rescued DOX-induced oxidative damage and apoptosis. Most importantly, SIRT1 activation could reduce DOX-induced SESN2 ubiquitination possibly through reducing the interaction of SESN2 with mouse double minute 2 (MDM2). The recovery of SESN2 stability in DOX-impaired primary cardiomyocytes by SIRT1 was confirmed by Mdm2-siRNA transfection. Taken together, our findings indicate that disrupting the interaction between SESN2 and MDM2 by SIRT1 to reduce the ubiquitination of SESN2 is a novel regulatory mechanism for protecting hearts from DOX-induced cardiotoxicity and suggest that the activation of SIRT1-SESN2 axis has potential as a therapeutic approach to prevent DOX-induced cardiotoxicity.
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•DOX-induced cardiotoxicity is based on decreased SIRT1 and SESN2 levels.•SIRT1 activation improves DOX-induced cardiac oxidative stress and apoptosis.•The benefits of SIRT1 in DOX-impaired cardiac function require the activation of SESN2.•SIRT1 reduces ubiquitination and degradation of SESN2 via MDM2.
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Sestrin2 (Sesn2) is a powerful anti-oxidant that can prevent acute and chronic diseases. The role of Sesn2 has been thoroughly reviewed in liver, nervous system, and immune system ...diseases. However, there is a limited number of reviews that have summarized the effects of Sesn2 in heart and vascular diseases, and very less literature-based information is available on involvement of Sesn2 in renal and respiratory pathologies. This review summarizes the latest research on Sesn2 in multi-organ stress responses, with a particular focus on the protective role of Sesn2 in cardiovascular, respiratory, and renal diseases, emphasizing the potential therapeutic benefit of targeting Sesn2 in stress-related diseases.
Diabetes mellitus (DM) has been one of the largest health concerns of the 21st century due to the serious complications associated with the disease. Therefore, it is essential to investigate the ...pathogenesis of DM and develop novel strategies to reduce the burden of diabetic complications. Sirtuin 1 (SIRT1), a nicotinamide adenosine dinucleotide (NAD
)-dependent deacetylase, has been reported to not only deacetylate histones to modulate chromatin function but also deacetylate numerous transcription factors to regulate the expression of target genes, both positively and negatively. SIRT1 also plays a crucial role in regulating histone and DNA methylation through the recruitment of other nuclear enzymes to the chromatin. Furthermore, SIRT1 has been verified as a direct target of many microRNAs (miRNAs). Recently, numerous studies have explored the key roles of SIRT1 and other related epigenetic mechanisms in diabetic complications. Thus, this review aims to present a summary of the rapidly growing field of epigenetic regulatory mechanisms, as well as the epigenetic influence of SIRT1 on the development and progression of diabetic complications, including cardiomyopathy, nephropathy, and retinopathy.
Fibroblast growth factor 1 (FGF1) has a critical regulatory role in the development of the cardiovascular system (CVS) and is strongly associated with the progression or treatment of cardiovascular ...diseases (CVDs). However, the regulatory mechanisms of FGF1 in CVS and CVDs have not yet been fully elucidated. Therefore, this review article summarized the existing literature reports on the role of FGF1 in CVS under physiological and pathological conditions. First, the expression and physiological functions of endogenous FGF1 is fully demonstrated. Then, we analyzed the role of exogenous FGF1 in normal CVS and related pathological processes. Specifically, the potential signaling pathways might be mediated by FGF1 in CVDs treatment is discussed in detail. In addition, the barriers and feasible solutions for the application of FGF1 are further analyzed. Finally, we highlight therapeutic considerations of FGF1 for CVDs in the future. Thus, this article may be as a reference to provide some ideas for the follow-up research.
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A cumulative and progressively developing cardiomyopathy induced by adriamycin (ADR)-based chemotherapy is a major obstacle for its clinical application. However, there is a lack of safe and ...effective method to protect against ADR-induced cardiotoxicity. Here, we found that mRNA and protein levels of FGF1 were decreased in ADR-treated mice, primary cardiomyocytes and H9c2 cells, suggesting the potential effect of FGF1 to protect against ADR-induced cardiotoxicity. Then, we showed that treatment with a FGF1 variant (FGF1ΔHBS) with reduced proliferative potency significantly prevented ADR-induced cardiac dysfunction as well as ADR-associated cardiac inflammation, fibrosis, and hypertrophy. The mechanistic study revealed that apoptosis and oxidative stress, the two vital pathological factors in ADR-induced cardiotoxicity, were largely alleviated by FGF1ΔHBS treatment. Furthermore, the inhibitory effects of FGF1ΔHBS on ADR-induced apoptosis and oxidative stress were regulated by decreasing p53 activity through upregulation of Sirt1-mediated p53 deacetylation and enhancement of murine double minute 2 (MDM2)-mediated p53 ubiquitination. Upregulation of p53 expression or cardiac specific-Sirt1 knockout (Sirt1-CKO) almost completely abolished FGF1ΔHBS-induced protective effects in cardiomyocytes. Based on these findings, we suggest that FGF1ΔHBS may be a potential therapeutic agent against ADR-induced cardiotoxicity.
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•Cardiac expression of FGF1 were decreased by ADR treatment.•FGF1ΔHBS prevented ADR-induced cardiac structural abnormalities and dysfunction.•FGF1ΔHBS inhibited ADR-induced oxidative stress and apoptosis by deacetylating p53.•Deacetylated p53 induced by FGF1ΔHBS accelerated the ubiquitination of p53 by MDM2.
Magnetic fluid hyperthermia(MFH) promises to be a viable alternative in the treatment of localized cancerous tumors.The treatment consists of introducing nanoparticles as energy absorbent agents in ...tumor tissue under an oscillating magnetic field,where nanoparticles dissipate energy in the form of heat,causing a localized rise in the temperature and tumor cell death.Traditional magnetic fluid under study is artificial magnetic nanoparticles.This work seeks to introduce the new natural biologic magnetic material bacterial magnetosomes(BMs) to be used in MFH.Properties of magnetosomes and chemically synthesized magnetic nanoparticles(MNPs),such as morphology,magnetic properties and their heating effects under magnetic field were compared.Cytotoxicity studies using human breast cancer cells MCF-7 indicated that cell viability could be significantly decreased by the heat derived from BMs and MNPs under alternative magnetic field.Biocompatibility of BMs and MNPs was compared in terms of evaluating their acute toxicity in mice and their decomposition abilities in vitro,and it showed that magnetosomes exhibit a lower toxicity.These findings provide evidence for beneficial activities of magnetosomes in MFH and support the continued investigation of it to be applied in biomedicine.
The distribution of oil and gas resources in the South China Sea and adjacent areas is closely related to the structural pattern that helped to define the controlling effect of deep processes on ...oil‐bearing basins. Igneous rocks can record important information from deep processes. Deep structures such as faults, basin uplift and depression, Cenozoic basement and magnetic basement are all the results of energy exchange within the earth. The study of the relationship between igneous rocks and deep structures is of great significance for the study of the South China Sea. By using the minimum curvature potential field separation technique and the correlation analysis technique of gravitational and magnetic anomalies, the fusion of gravitational and magnetic data reflecting igneous rocks can be obtained, through which the igneous rocks with high susceptibility/high density or high susceptibility/low density can be identified. In this study area, igneous rocks do not develop in the Yinggehai basin, Qiongdongnan basin, Zengmu basin and Brunei‐Sabah basin, whilst igneous rocks with high susceptibility/high density or high susceptibility/low density are widely‐developed in other basins. In undeveloped igneous areas, faults are also undeveloped, the Cenozoic thickness is greater, the magnetic basement depth is greater and the Cenozoic thickness is highly positively correlated with the magnetic basement depth. In igneously developed regions, the distribution pattern of the Qiongtai block is mainly controlled by primary faults, while the distribution of the Zhongxisha block, Xunta block and Yongshu‐Taiping block is mainly controlled by secondary faults, the Cenozoic thickness having a low correlation with the depth of the magnetic basement.
Based on the drilling data of the Silurian Longmaxi Formation in the Sichuan Basin and periphery, SW China, the Ro lower limits and essential features of the carbonization of organic matter in ...over-high maturity marine shale were examined using laser Raman, electrical and physical property characterization techniques. Three preliminary conclusions are drawn: (1) The lower limit of Ro for the carbonization of Type I-II1 organic matter in marine shale is 3.5%; when the Ro is less than 3.4%, carbonization of organic matter won't happen in general; when the Ro ranges from 3.4% to 3.5%, non-carbonization and weak carbonization of organic matter may coexist; when the Ro is higher than 3.5%, the carbonization of organic matter is highly likely to take place. (2) Organic-rich shale entering carbonization phase have three basic characteristics: log resistivity curve showing a general “slender neck” with low-ultralow resistance response, Raman spectra showing a higher graphite peak, and poor physical property (with matrix porosity of only less than 1/2 of the normal level). (3) The quality damage of shale reservoir caused by the carbonization of organic matter is almost fatal, which primarily manifests in depletion of hydrocarbon generation capacity, reduction or disappearance of organic pores and intercrystalline pores of clay minerals, and drop of adsorption capacity to natural gas. Therefore, the lower limit of Ro for the carbonization of Type I-II1 organic matter should be regarded as the theoretically impassable red line of shale gas exploration in the ancient marine shale formations. The organic-rich shale with low-ultralow resistance should be evaluated effectively in area selection to exclude the high risk areas caused by the carbonization of organic matter. The target organic-rich shale layers with low-ultralow resistance drilled during exploration and development should be evaluated on carbonization level of organic matter, and the deployment plan should be adjusted according to the evaluation results in time.
Based on the Qiliao section of the Upper Ordovician Wufeng Formation – Lower Silurian Longmaxi Formation in Shizhu, Chongqing city, the development characteristics of bentonite in eastern Sichuan ...Basin was examined systematically, and its geological significance and scientific value were analyzed. The main understandings are as follows: (1) Six bentonite dense layers were found in the Qiliao section, mainly occurring in 6 graptolitic belts of the Katian, Rhuddanian and Aeronian. Most of the bentonite dense layers showed obvious increase in clay, peak response of GR curve, and indistinct relationship between volcanic ash and total organic carbon (TOC). (2) The bentonite dense layers of Longmaxi Formation were widely distributed in eastern Sichuan Basin and its periphery, and generally showed GR peak, which can be an important reference interface for dividing the bottom boundary of the Coronograptus cyphus belt and the top boundary of the Rhuddanian in eastern Sichuan Basin and western Hubei province. (3) Taking the bentonite dense layers as the stratification basis of the Rhuddanian and Aeronian, it was determined that the sediment thickness of the Rhuddanian in the eastern Sichuan depression was generally 10–40 m, but only the upper part of the Coronograptus cyphus belt was deposited in the hinderland of Yichang Uplift, and the sedimentary thickness was only 3–7 m. (4) In the hinderland of the Yichang Uplift, at least five and a half graptolitic belts were missing in Wufeng Formation – Rhuddanian, and the deposition time of Rhuddanian was less than 0.4 Ma. (5) The bentonite dense layers were important sedimentary responses to the strong deflection of the Yangtze basin at the turn of the Ordovician–Silurian, which suggested that four tectonic activity periods existed in the eastern Sichuan depression, including the early stage of the depression, the middle-late stage of the depression, the early stage of the foreland flexure and the development stage of the foreland flexure. The high-quality shale was mainly developed from the early stage to the middle-late stage in the depression.
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