scholarly journals Development of Triiodothyronine Polymeric Nanoparticles for Targeted Delivery in the Cardioprotection against Ischemic Insult

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1713
Author(s):  
Ozlem Ozen Karakus ◽  
Noureldien H. E. Darwish ◽  
Thangirala Sudha ◽  
Taher A. Salaheldin ◽  
Kazutoshi Fujioka ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Hormone Receptors ◽  
Nuclear Translocation ◽  
Polymeric Nanoparticles ◽  
Myocardial Damage ◽  
Protective Role ◽  
Ischemic Heart ◽  
New Strategy

Ischemic heart disease is the main cause of death globally. Cardioprotection is the process whereby mechanisms that reduce myocardial damage, and activate protective factors, contribute to the preservation of the heart. Targeting these processes could be a new strategy in the treatment of post-ischemic heart failure (HF). Triiodothyronine (T3) and thyroxine (T4), which have multiple effects on the heart, prevent myocardial damage. This study describes the formulation, and characterization, of chemically modified polymeric nanoparticles incorporating T3, to target the thyroid hormone receptors. Modified T3 was conjugated to polylactide-co-glycolide (PLGA) to facilitate T3 delivery and restrict its nuclear translocation. Modified T3 and PLGA-T3 was characterized with 1H-NMR. The protective role of synthesized phosphocreatine (PCr) encapsulated PLGA-T3 nanoparticles (PLGA-T3/PCr NPs) and PLGA-T3 nanoparticles (PLGA-T3 NPs) in hypoxia-mediated cardiac cell insults was investigated. The results showed that PLGA-T3/PCr NPs represent a potentially new therapeutic agent for the control of tissue damage in cardiac ischemia and resuscitation.

scholarly journals Development of PLGA-Triiodothyronine Nanoparticles for Targeted Delivery in the Cardioprotection Against Ischemic Insult

2021 ◽  
Author(s):  
Ozlem Ozen Karakus ◽  
Noureldien H. E. Darwish ◽  
Taher Salaheldin ◽  
P. C. Taylor Dickinson ◽  
Brian Weil ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Hormone Receptors ◽  
Polymeric Nanoparticles ◽  
Myocardial Damage ◽  
Protective Role ◽  
Ischemic Heart ◽  
H Nmr ◽  
New Strategy

Abstract Background: Ischemic heart disease is the main cause of death globally. Cardioprotection is the process whereby mechanisms that reduce myocardial damage, and activate protective factors, contribute to the preservation of the heart. Targeting these processes could be a new strategy in the treatment of post-ischemic heart failure (HF). Triiodothyronine (T3) and thyroxine (T4), which have multiple effects on the heart, prevent myocardial damage. Results: This study describes the formulation, and characterization, of chemically modified polymeric nanoparticles incorporating T3, to target the thyroid hormone receptors. Modified T3 was conjugated to polylactide-co-glycolide (PLGA) to facilitate the active targeting of PLGA-T3. Modified T3 and PLGA-T3 was characterized with 1H-NMR. Protective role of synthesized Phosphocreatine (PCr) encapsulated PLGA-T3 nanoparticles (PLGA-T3/PCr NPs) and PLGA-T3 nanoparticles (PLGA-T3 NPs) in hypoxia-mediated cardiac cell insults were investigated. Conclusions: Data demonstrated that PLGA-T3/PCr NPs represent a potentially new therapeutic for the control of tissue damage in cardiac ischemia and resuscitation.

Overexpression of miR-431 attenuates hypoxia/reoxygenation-induced myocardial damage via autophagy-related 3

2020 ◽  
Author(s):  
Kang Zhou ◽  
Yan Xu ◽  
Qiong Wang ◽  
Lini Dong
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Protective Role ◽  
Human Cardiomyocytes ◽  
Hypoxia Reoxygenation

Abstract Myocardial injury is still a serious condition damaging the public health. Clinically, myocardial injury often leads to cardiac dysfunction and, in severe cases, death. Reperfusion of the ischemic myocardial tissues can minimize acute myocardial infarction (AMI)-induced damage. MicroRNAs are commonly recognized in diverse diseases and are often involved in the development of myocardial ischemia/reperfusion injury. However, the role of miR-431 remains unclear in myocardial injury. In this study, we investigated the underlying mechanisms of miR-431 in the cell apoptosis and autophagy of human cardiomyocytes in hypoxia/reoxygenation (H/R). H/R treatment reduced cell viability, promoted cell apoptotic rate, and down-regulated the expression of miR-431 in human cardiomyocytes. The down-regulation of miR-431 by its inhibitor reduced cell viability and induced cell apoptosis in the human cardiomyocytes. Moreover, miR-431 down-regulated the expression of autophagy-related 3 (ATG3) via targeting the 3ʹ-untranslated region of ATG3. Up-regulated expression of ATG3 by pcDNA3.1-ATG3 reversed the protective role of the overexpression of miR-431 on cell viability and cell apoptosis in H/R-treated human cardiomyocytes. More importantly, H/R treatments promoted autophagy in the human cardiomyocytes, and this effect was greatly alleviated via miR-431-mimic transfection. Our results suggested that miR-431 overexpression attenuated the H/R-induced myocardial damage at least partly through regulating the expression of ATG3.

scholarly journals Preparation and Characterization of Water-Based Nano-Perfumes

Nanomaterials ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. 981 ◽  
Author(s):  
Małgorzata Miastkowska ◽  
Elwira Lasoń ◽  
Elżbieta Sikora ◽  
Katarzyna Wolińska-Kennard
Keyword(s):  
Droplet Size ◽  
Interfacial Area ◽  
High Energy ◽  
Protective Role ◽  
Food Industries ◽  
Low Viscosity ◽  
Oil In Water ◽  
Water Based

The application of nanoemulsions as a novel delivery system for lipophilic materials, such as essential oils, flavors, and fragrances is one of the growing technologies used in cosmetic, pharmaceutical, and food industries. Their characteristic properties, like small droplet size with high interfacial area, transparent or semi-transparent appearance, low viscosity, and high kinetic stability, make them a perfect vehicle for fragrances, in the perfume industry. They could be a great alternative to water-based perfumes, without alcohol, and solve problems related to the oxidation and low bioavailability of fragrances with other non-alcoholic vehicles of perfumes like pomades or gels. The aim of our study was to develop stable Oil-in-Water (O/W) nanoemulsions that are compatible with selected fragrance compositions, without ethanol, polyols, and ionic surfactants, and to study their physicochemical, microbiological, and dermatological properties. The nano-perfume systems were obtained with a low-energy (Phase Inversion Composition; PIC) and with a high-energy (ultrasound, US) method, taking into account the possibility of moving from the laboratory scale to an industrial scale. The optimized nano-perfume formulations, prepared with different methods, yielded the same physicochemical properties (stability, medium droplet size of the inner phase, polydispersity, viscosity, surface tension, pH, density). Stable systems were obtained with a fragrance composition concentration within 6–15% range. These formulations had a low viscosity and a pH suitable for the skin. Moreover, the obtained results confirmed the protective role of nanoemulsions. The peroxide number measurement (POV) showed that the tested fragrance compositions had a high chemical stability. The results of the microbiological tests confirmed that the obtained products were free of microbiological contamination and were appropriately preserved. The dermatological test results confirmed the safety of the developed preparations.

scholarly journals Trehalose Alleviates Crystalline Silica-Induced Pulmonary Fibrosis via Activation of the TFEB-Mediated Autophagy-Lysosomal System in Alveolar Macrophages

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 122 ◽  
Author(s):  
Xiu He ◽  
Shi Chen ◽  
Chao Li ◽  
Jiaqi Ban ◽  
Yungeng Wei ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Alveolar Macrophages ◽  
Nuclear Translocation ◽  
Protective Role ◽  
Crystalline Silica ◽  
Autophagic Flux ◽  
Lysosomal System

Silicosis is an occupational lung disease characterized by persistent inflammation and irreversible fibrosis. Crystalline silica (CS) particles are mainly phagocytized by alveolar macrophages (AMs), which trigger apoptosis, inflammation, and pulmonary fibrosis. Previously, we found that autophagy-lysosomal system dysfunction in AMs was involved in CS-induced inflammation and fibrosis. Induction of autophagy and lysosomal biogenesis by transcription factor EB (TFEB) nuclear translocation can rescue fibrotic diseases. However, the role of TFEB in silicosis is unknown. In this study, we found that CS induced TFEB nuclear localization and increased TFEB expression in macrophages both in vivo and in vitro. However, TFEB overexpression or treatment with the TFEB activator trehalose (Tre) alleviated lysosomal dysfunction and enhanced autophagic flux. It also reduced apoptosis, inflammatory cytokine levels, and fibrosis. Both pharmacologically inhibition of autophagy and TFEB knockdown in macrophages significantly abolished the antiapoptotic and anti-inflammatory effects elicited by either TFEB overexpression or Tre treatment. In conclusion, these results uncover a protective role of TFEB-mediated autophagy in silicosis. Our study suggests that restoration of autophagy-lysosomal function by Tre-induced TFEB activation may be a novel strategy for the treatment of silicosis.

scholarly journals Pretreatment with Roxadustat (FG-4592) Attenuates Folic Acid-Induced Kidney Injury through Antiferroptosis via Akt/GSK-3β/Nrf2 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Xue Li ◽  
Yu Zou ◽  
Jia Xing ◽  
Yuan-Yuan Fu ◽  
Kai-Yue Wang ◽  
...  
Keyword(s):  
Renal Function ◽  
Folic Acid ◽  
Nuclear Translocation ◽  
Early Stage ◽  
Kidney Injury ◽  
Protective Role ◽  
Iron Accumulation ◽  
Inflammatory Factors ◽  
Nrf2 Activation

Folic acid- (FA-) induced kidney injury is characterized by the tubule damage due to the disturbance of the antioxidant system and subsequent interstitial fibrosis. FG-4592 is an inhibitor of prolyl hydroxylase of hypoxia-inducible factor (HIF), an antioxidant factor. The present study investigated the protective role of FG-4592 pretreatment at the early stage of the kidney injury and long-term impact on the progression of renal fibrosis. FG-4592 was administrated two days before FA injection in mice. On the second day after FA injection, the mice with FG-4592 pretreatment showed an improved renal function, compared with those without FG-4592 pretreatment, indicated by biochemical and histological parameters; meanwhile, the cellular content of iron, malondialdehyde, and 4-hydroxynonenal histologically decreased, implying the suppression of iron accumulation and lipid peroxidation. Simultaneously, upregulation of HIF-1α was found, along with Nrf2 activation, which was reflected by increased nuclear translocation and high-expression of downstream proteins, including heme-oxygenase1, glutathione peroxidase4, and cystine/glutamate transporter, as well as ferroportin. Correspondingly, the elevated levels of antioxidative enzymes and glutathione, as well as reduced iron accumulation, were observed, suggesting a lower risk of occurrence of ferroptosis with FG-4592 pretreatment. This was confirmed by reversed pathological parameters and improved renal function in FA-treated mice with the administration of ferrostatin-1, a specific ferroptosis inhibitor. Furthermore, a signal pathway study indicated that Nrf2 activation was associated with increased phosphorylation of Akt and GSK-3β, verified by the use of an inhibitor of the PI3K that phosphorylates Akt. Moreover, FG-4592 pretreatment also decreased macrophage infiltration and expression of inflammatory factors TNF-α and IL-1β. On the 14th day after FA injection, FG-4592 pretreatment decreased collagen deposition and expression of fibrosis biomarkers. These findings suggest that the protective role of FG-4592 pretreatment is achieved mainly by decreasing ferroptosis at the early stage of FA-induced kidney injury via Akt/GSK-3β-mediated Nrf2 activation, which retards the fibrosis progression.

scholarly journals Oxidative stress-induced FABP5 S-glutathionylation protects against acute lung injury by suppressing inflammation in macrophages

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuxian Guo ◽  
Yaru Liu ◽  
Shihao Zhao ◽  
Wangting Xu ◽  
Yiqing Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Protein S ◽  
Protective Role ◽  
Fatty Acid Binding ◽  
Proteomics Approach

AbstractOxidative stress contributes to the pathogenesis of acute lung injury. Protein S-glutathionylation plays an important role in cellular antioxidant defense. Here we report that the expression of deglutathionylation enzyme Grx1 is decreased in the lungs of acute lung injury mice. The acute lung injury induced by hyperoxia or LPS is significantly relieved in Grx1 KO and Grx1fl/flLysMcre mice, confirming the protective role of Grx1-regulated S-glutathionylation in macrophages. Using a quantitative redox proteomics approach, we show that FABP5 is susceptible to S-glutathionylation under oxidative conditions. S-glutathionylation of Cys127 in FABP5 promotes its fatty acid binding ability and nuclear translocation. Further results indicate S-glutathionylation promotes the interaction of FABP5 and PPARβ/δ, activates PPARβ/δ target genes and suppresses the LPS-induced inflammation in macrophages. Our study reveals a molecular mechanism through which FABP5 S-glutathionylation regulates macrophage inflammation in the pathogenesis of acute lung injury.

scholarly journals 4R Tau Modulates Cocaine-Associated Memory Through Adult Hippocampal Neurogenesis

2020 ◽  
Author(s):  
Hongchun Li ◽  
Wei Xu ◽  
Denian Wang ◽  
Qiyao Fang ◽  
Liang Wang ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Underlying Mechanism ◽  
Memory Formation ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Self Administration ◽  
New Strategy ◽  
Contextual Stimuli ◽  
Phosphoinositide 3 Kinase

Abstract Background: Drug memory that generally develops with drug-paired contextual stimuli and drug administration is critical for the development, persistence and relapse of drug addiction. Previous studies have suggested that adult hippocampal neurogenesis (AHN) plays a role in cocaine memory formation; however, the underlying mechanism is not fully understood.Methods: Conditioned place preference (CPP), self-administration and locomotor activity were used to investigate the role of Tau in cocaine-associated memory formation. Virus-mediated gene transfer, western blot, immunohistochemistry, flow cytometry analysis, Tau-interacting proteomics, co-immunoprecipitation, and mutation of 4R Tau were performed. Results: Hippocampal expression of Tau was significantly decreased during the cocaine-associated memory formation. Genetic overexpression of four microtubule-binding repeats Tau (4R Tau) in the hippocampus disrupted cocaine memory by suppressing AHN. Furthermore, 4R Tau directly interacted with phosphoinositide 3-kinase (PI3K)-p85 and impaired its nuclear translocation and PI3K-AKT signaling, processes required for hippocampal neuron proliferation. Conclusions: 4R Tau modulates cocaine memory formation by disrupting AHN, suggesting a novel mechanism underlying cocaine memory formation and provide a new strategy for the treatment of cocaine addiction.

The Protective Role of Poly(Borosiloxanes)-Derived Ceramics in Carbon Fiber Composites

2008 ◽  
Vol 587-588 ◽  
pp. 182-186 ◽  
Author(s):  
Renato Luiz Siqueira ◽  
Luiz Claudio Pardini ◽  
Inez Valéria Pagotto Yoshida ◽  
Marco Antônio Schiavon
Keyword(s):  
Carbon Fiber ◽  
Carbon Fibers ◽  
Thermal Protection ◽  
Ceramic Matrix Composites ◽  
Thermal Characterization ◽  
Protective Role ◽  
Carbon Fiber Composites ◽  
Matrix Composites

This work reports the synthesis and thermal characterization of poly(borosiloxanes) (PBS) derived from methyltrietoxysilane (MTES) and vinyltriethoxysilane (VTES), aiming to use these polymers as precursors of ceramic matrices for the protection of carbon fibers in ceramic matrix composites (CMCs). The resulting materials exhibited better thermal stability than the carbon fiber, especially the Cfiber/SiBCO composite derived of the methyltriethoxysilane (MTES) system prepared with a B/Si ratio of 0.5. This study showed that poly(borosiloxanes) are promising materials for the oxidation protection of carbon fibers, and consequently for thermal protection systems.

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