The Bcl2/adenovirus E1B 19-kDa interacting protein 3 (Bnip3) is an atypical BH3-only protein that is associated with mitochondrial dysfunction and cell death. Bnip3 is also a potent inducer of ...mitochondrial autophagy, and in this study we have investigated the mechanisms by which Bnip3 induces autophagy in cardiac myocytes. We found that Bnip3 induced mitochondrial translocation of dynamin-related protein 1 (Drp1), a protein involved in mitochondrial fission in adult myocytes. Drp1-mediated mitochondrial fission correlated with increased autophagy, and inhibition of Drp1 reduced Bnip3-mediated autophagy. Overexpression of Drp1K38E, a dominant negative of Drp1, or mitofusin 1 prevented mitochondrial fission and autophagy by Bnip3. Also, inhibition of mitochondrial fission or autophagy resulted in increased death of myocytes overexpressing Bnip3. Moreover, Bnip3 promoted translocation of the E3 ubiquitin ligase Parkin to mitochondria, which was prevented in the presence of a Drp1 inhibitor. Interestingly, induction of autophagy by Bnip3 was reduced in Parkin-deficient myocytes. Thus our data suggest that induction of autophagy in response to Bnip3 is a protective response activated by the cell that involves Drp1-mediated mitochondrial fission and recruitment of Parkin.
Apoptosis plays a key role in the pathogenesis in a variety of cardiovascular diseases due to loss of terminally differentiated cardiac myocytes. Cardiac myocytes undergoing apoptosis have been ...identified in tissue samples from patients suffering from myocardial infarction, diabetic cardiomyopathy, and end-stage congestive heart failure. Apoptosis is a highly regulated program of cell death and can be mediated by death receptors in the plasma membrane, as well as the mitochondria and the endoplasmic reticulum. The cell death program is activated in cardiac myocytes by various stressors including cytokines, increased oxidative stress and DNA damage. Many studies have demonstrated that inhibition of apoptosis is cardioprotective and can prevent the development of heart failure. This review provides a current overview of the evidence of apoptosis in cardiovascular diseases and discusses the molecular pathways involved in cardiac myocyte apoptosis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The term, "multiple chronic diseases" (MCD), describes a patient with two or more chronic conditions simultaneously at the same time. Compared with general chronic diseases, it is linked to poorer ...health outcomes, more difficult clinical management, and higher medical expenses. Several existing MCD guidelines support a healthy lifestyle including regular physical activities but do not include specific exercise therapy recommendations. This study aimed to understand the prevalence and model of MCD in middle-aged and elderly South Koreans by comparing MCD characteristics with exercise habits, to provide a theoretical basis for the implementation of exercise therapy in these patients.
The data of 8477 participants aged > 45 years from the "2020 Korean Health Panel Survey" were used to analyze the current status of MCD in the middle-aged and elderly. The Chi-square test for categorical variables and the t-test for continuous variables. the used software was IBM SPSS Statistics 26.0 and IBM SPSS Modeler 18.0.
In this study, the morbidity rate of MCD was 39.1%. Those with MCD were more likely to be female (p < 0.001), seniors over 65 years of age (p < 0.001), with low education level, no regular exercise behavior (p < 0.01). Chronic renal failure (93.9%), depression (90.4%), and cerebrovascular disease (89.6%) were the top three diseases identified in patients with MCD. A total of 37 association rules were identified for the group of individuals who did not engage in regular exercise. This equated to 61% more than that of the regular exercise group, who showed only 23 association rules. In the extra association rules, cardiovascular diseases (150%), spondylosis (143%), and diabetes (125%) are the three chronic diseases with the highest frequency increase.
Association rule analysis is effective in studying the relationship between various chronic diseases in patients with MCD. It also effectively helps with the identification of chronic diseases that are more sensitive to regular exercise behaviors. The findings from this study may be used to formulate more appropriate and scientific exercise therapy for patients with MCD.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It is known that loss-of-function mutations in the gene encoding Parkin lead to development of Parkinson disease. Recently, Parkin was found to play an important role in the removal of dysfunctional ...mitochondria via autophagy in neurons. Although Parkin is expressed in the heart, its functional role in this tissue is largely unexplored. In this study, we have investigated the role of Parkin in the myocardium under normal physiological conditions and in response to myocardial infarction. We found that Parkin-deficient (Parkin−/−) mice had normal cardiac function for up to 12 months of age as determined by echocardiographic analysis. Although ultrastructural analysis revealed that Parkin-deficient hearts had disorganized mitochondrial networks and significantly smaller mitochondria, mitochondrial function was unaffected. However, Parkin−/− mice were much more sensitive to myocardial infarction when compared with wild type mice. Parkin−/− mice had reduced survival and developed larger infarcts when compared with wild type mice after the infarction. Interestingly, Parkin protein levels and mitochondrial autophagy (mitophagy) were rapidly increased in the border zone of the infarct in wild type mice. In contrast, Parkin−/− myocytes had reduced mitophagy and accumulated swollen, dysfunctional mitochondria after the infarction. Overexpression of Parkin in isolated cardiac myocytes also protected against hypoxia-mediated cell death, whereas nonfunctional Parkinson disease-associated mutants ParkinR42P and ParkinG430D had no effect. Our results suggest that Parkin plays a critical role in adapting to stress in the myocardium by promoting removal of damaged mitochondria.
Background: The functional importance of Parkin in the heart is unknown.
Results: Parkin deficiency results in increased susceptibility to myocardial infarction.
Conclusion: Parkin is important in adapting to stress.
Significance: Our studies will advance our knowledge of Parkin in cardiovascular disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Copper nanoparticles are being given considerable attention as of late due to their interesting properties and potential applications in many areas of industry. One such exploitable use is as the ...major constituent of conductive inks and pastes used for printing various electronic components. In this study, copper nanoparticles were synthesized through a relatively large-scale (5 l), high-throughput (0.2 M) process. This facile method occurs through the chemical reduction of copper sulfate with sodium hypophosphite in ethylene glycol within the presence of a polymer surfactant (PVP), which was included to prevent aggregation and give dispersion stability to the resulting colloidal nanoparticles. Reaction yields were determined to be quantitative while particle dispersion yields were between 68 and 73%. The size of the copper nanoparticles could be controlled between 30 and 65 nm by varying the reaction time, reaction temperature, and relative ratio of copper sulfate to the surfactant. Field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) images of the particles revealed a spherical shape within the reported size regime, and x-ray analysis confirmed the formation of face-centered cubic (FCC) metallic copper. Furthermore, inkjet printing nanocopper inks prepared from the polymer-stabilized copper nanoparticles onto polyimide substrates resulted in metallic copper traces with low electrical resistivities (≥3.6 µΩ cm, or ≥2.2 times the resistivity of bulk copper) after a relatively low-temperature sintering process (200 °C for up to 60 min).
Conducting and superparamagnetic monodispersed Fe
3O
4–poly(3, 4-ethylenedioxythiophene) core–shell composite nanoparticles with the size about 15
nm, were synthesized via an
in situ chemical ...oxidative polymerization in the micellar solution of lignosulfonic acid (LSA).
Core–shell nanocomposites composed of iron oxide (Fe
3O
4) nanoparticles and conjugated polymer, poly(3, 4-ethylenedioxythiophene) (PEDOT), were successfully synthesized from a simple and inexpensive
in situ chemical oxidative polymerization of EDOT with Fe
3O
4 nanoparticles in the micellar solution of lignosulfonic acid (LSA) which serves as both a surfactant and a dopant. These nanocomposites (Fe
3O
4–PEDOT) were subsequently characterized for morphological, crystalline, structural, electrical and magnetic properties by high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), four-probe meter and superconductor quantum interference device (SQUID), respectively. Results show that the nanocomposites have a spherical core–shell shape, are ∼10
nm in size and are superparamagnetic with good magnetic saturation and good electrical conductivities. Existence of Fe
3O
4 in the nanocomposites was confirmed by using Energy dispersive X-ray photoelectron spectroscopy (EDAX) and X-ray photoelectron microscopy (XPS). We also investigated a possible formation mechanism of the core–shell nanocomposites, and the effect of Fe
3O
4 nanoparticles on the electro-magnetic properties of the nanocomposites. Such novel conducting and superparamagnetic composite nanomaterials can be applied to sensors, magnetic data storage, electro-magnetic resonance wave absorption, etc.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Myeloid cell leukemia-1 (MCL-1) is an anti-apoptotic BCL-2 protein that is up-regulated in several human cancers. MCL-1 is also highly expressed in myocardium, but its function in myocytes has not ...been investigated. We generated inducible, cardiomyocyte-specific Mcl-1 knockout mice and found that ablation of Mcl-1 in the adult heart led to rapid cardiomyopathy and death. Although MCL-1 is known to inhibit apoptosis, this process was not activated in MCL-1-deficient hearts. Ultrastructural analysis revealed disorganized sarcomeres and swollen mitochondria in myocytes. Mitochondria isolated from MCL-1-deficient hearts exhibited reduced respiration and limited Ca(2+)-mediated swelling, consistent with opening of the mitochondrial permeability transition pore (mPTP). Double-knockout mice lacking MCL-1 and cyclophilin D, an essential regulator of the mPTP, exhibited delayed progression to heart failure and extended survival. Autophagy is normally induced by myocardial stress, but induction of autophagy was impaired in MCL-1-deficient hearts. These data demonstrate that MCL-1 is essential for mitochondrial homeostasis and induction of autophagy in the heart. This study also raises concerns about potential cardiotoxicity for chemotherapeutics that target MCL-1.
An efficient synthesis is used for the first time to prepare CaCu3Ti4−xWxO12 (x = 0.01, 0.03, and 0.05) electroceramics for energy storage capacitors. CaCu3Ti4−xWxO12 ceramics are synthesized via ...flame synthesis of metal nitrates precursors in nonaqueous solution using cheap, stable, and insoluble solid TiO2 powder. The pathway yielded a CaCu3Ti4O12 (CCTO) phase with the traces of CuO and CaTiO3 sintered at 1050°C for 30 h. The SEM micrograph shows the grains with smooth surfaces associated with cubical appearance and the size range of 1.5–7, 2.0–7.5, and 2.0–8.0 μm for CCTWO01, CCTWO03, and CCTWO05, respectively. The EDX and XPS analyses show the presence of Ca, Cu, Ti, W, and O elements confirming the purity of these ceramics. The complex impedance and modulus (M) spectroscopy show that the dielectric constant (εr) values of the W‐doped CCTO were dominantly affected by the electrical properties of the grain boundary, which is also evident from the SEM micrographs. The grain‐boundary resistance decreased with increasing tungsten content. The activation energies for the grain boundaries were calculated from the impedance and modulus data using the slope of the ln τ versus 1/T and were found to be in the range 0.62–0.67 eV.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Bnip3 is a pro-apoptotic BH3-only protein which is associated with mitochondrial dysfunction and cell death. Bnip3 is also a potent inducer of autophagy in many cells. In this study, we have ...investigated the mechanism by which Bnip3 induces autophagy in adult cardiac myocytes. Overexpression of Bnip3 induced extensive autophagy in adult cardiac myocytes. Fluorescent microscopy studies and ultrastructural analysis revealed selective degradation of mitochondria by autophagy in myocytes overexpressing Bnip3. Oxidative stress and increased levels of intracellular Ca2+ have been reported by others to induce autophagy, but Bnip3-induced autophagy was not abolished by antioxidant treatment or the Ca2+ chelator BAPTA-AM. We also investigated the role of the mitochondrial permeability transition pore (mPTP) in Bnip3-induced autophagy. Although the mPTP has previously been implicated in the induction of autophagy and selective removal of damaged mitochondria by autophagosomes, mitochondria sequestered by autophagosomes in Bnip3-treated cardiac myocytes had not undergone permeability transition, and treatment with the mPTP inhibitor cyclosporine A did not inhibit mitochondrial autophagy in cardiac myocytes. Moreover, cyclophilin D (cypD) is an essential component of the mPTP and Bnip3 induced autophagy to the same extent in embryonic fibroblasts isolated from wild-type and cypD-deficient mice. These results support a model where Bnip3 induces selective removal of the mitochondria in cardiac myocytes, and that Bnip3 triggers induction of autophagy independent of Ca2+, ROS generation, and mPTP opening.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Luminescent inorganic lead halide perovskite nanoparticles lack stability in aqueous solutions, limiting their application to optical sensors. Here, hybrid CsPbBr
-loaded MIP nanogels were developed ...with enhanced stability in aqueous media. Multifunctional MIP nanogels with antioxidant function and hydrophobic cavities were synthesized from HEMA derivatives in the presence of roxithromycin as a template. The CsPbBr
nanoparticles were loaded into pre-synthesized MIP nanogels via in-situ synthesis with a size distribution of 200 nm. The developed CsPbBr
-nanogel exhibits excellent stability to air/moisture and enhanced stability toward an aqueous solvent. The developed CsPbBr
-loaded MIP nanogels showed a selective and sensitive detection of ROX with a limit of detection calculated to be 1.7 × 10
μg/mL (20.6 pM). The developed CsPbBr
-loaded MIP antioxidant-nanogels were evaluated on practical application for the quantitative determination of ROX antibiotic in animal-derived food products with excellent analytical performance. The detection of ROX in animal-derived food products showed good recovery results, making them an ideal candidate for sensing ROX.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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