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Aims: Cardiac ischaemia/reperfusion (I/R) injury remains a critical issue in the therapeutic management of ischaemic heart failure. Although mild hypothermia has a protective effect on cardiac I/R injury, more rapid and safe methods that can obtain similar results to hypothermia therapy are required. 2‐Methyl‐2‐thiazoline (2MT), an innate fear inducer, causes mild hypothermia resulting in resistance to critical hypoxia in cutaneous or cerebral I/R injury. The aim of this study is to demonstrate the protective effect of systemically administered 2MT on cardiac I/R injury and to elucidate the mechanism underlying this effect. Methods and results: A single subcutaneous injection of 2MT (50 mg/kg) was given prior to reperfusion of the I/R injured 10 week‐old male mouse heart and its efficacy was evaluated 24 h after the ligation of the left anterior descending coronary artery. 2MT preserved left ventricular systolic function following I/R injury (ejection fraction, %: control 37.9 ± 6.7, 2MT 54.1 ± 6.4, P < 0.01). 2MT also decreased infarct size (infarct size/ischaemic area at risk, %: control 48.3 ± 12.1, 2MT 25.6 ± 4.2, P < 0.05) and serum cardiac troponin levels (ng/mL: control 8.9 ± 1.1, 2MT 1.9 ± 0.1, P < 0.01) after I/R. Moreover, 2MT reduced the oxidative stress‐exposed area within the heart (%: control 25.3 ± 4.7, 2MT 10.8 ± 1.4, P < 0.01). These results were supported by microarray analysis of the mouse hearts. 2MT induced a transient, mild decrease in core body temperature (°C: −2.4 ± 1.4), which gradually recovered over several hours. Metabolome analysis of the mouse hearts suggested that 2MT minimized energy metabolism towards suppressing oxidative stress. Furthermore, 18F‐fluorodeoxyglucose‐positron emission tomography/computed tomography imaging revealed that 2MT reduced the activity of brown adipose tissue (standardized uptake value: control 24.3 ± 6.4, 2MT 18.4 ± 5.8, P < 0.05). 2MT also inhibited mitochondrial respiration and glycolysis in rat cardiomyoblasts. Conclusions: We identified the cardioprotective effect of systemically administered 2MT on cardiac I/R injury by sparing energy metabolism with reversible hypothermia. Our results highlight the potential of drug‐induced hypothermia therapy as an adjunct to coronary intervention in severe ischaemic heart disease. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction is a leading cause of death among single organ diseases. Despite successful reperfusion therapy, ischaemia reperfusion injury (IRI) can induce oxidative stress (OS), cardiomyocyte apoptosis, autophagy and release of inflammatory cytokines, resulting in increased infarct size. In IRI, mitochondrial dysfunction is a key factor, which involves the production of reactive oxygen species, activation of inflammatory signalling cascades or innate immune responses, and apoptosis. Therefore, intercellular mitochondrial transfer could be considered as a promising treatment strategy for ischaemic heart disease. However, low transfer efficiency is a challenge in clinical settings. We previously reported uptake of isolated exogenous mitochondria into cultured cells through co‐incubation, mediated by macropinocytosis. Here, we report the use of transactivator of transcription dextran complexes (TAT‐dextran) to enhance cellular uptake of exogenous mitochondria and improve the protective effect of mitochondrial replenishment in neonatal rat cardiomyocytes (NRCMs) against OS. TAT‐dextran–modified mitochondria (TAT‐Mito) showed a significantly higher level of cellular uptake. Mitochondrial transfer into NRCMs resulted in anti‐apoptotic capability and prevented the suppression of oxidative phosphorylation in mitochondria after OS. Furthermore, TAT‐Mito significantly reduced the apoptotic rates of cardiomyocytes after OS, compared to simple mitochondrial transfer. These results indicate the potential of mitochondrial replenishment therapy in OS‐induced myocardial IRI. [ABSTRACT FROM AUTHOR]

Whole organ tissue engineering for various organs, including the heart, lung, liver, and kidney, has demonstrated promising results for end-stage organ failure. However, the sodium dodecyl sulfate (SDS)-based protocol for standard decellularization has drawbacks such as clot formation in vascularized transplantation and poor cell engraftment in recellularization procedures. Preservation of the surface milieu of extracellular matrices (ECMs) might be crucial for organ generation based on decellularization/recellularization engineering. We examined a novel detergent, sodium lauryl ether sulfate (SLES), to determine whether it could overcome the drawbacks associated with SDS using rat heart and kidney. Both organs were perfused in an antegrade fashion with either SLES or SDS. Although immunohistochemistry for collagen I, IV, laminin, and fibronectin showed similar preservation in both detergents, morphological analysis using scanning electron microscopy and an assay of glycosaminoglycan content on ECMs showed that SLES-treated tissues had better-preserved ECMs than SDS-treated tissues. Mesenteric transplantation revealed SLES did not induce significant inflammation, as opposed to SDS. Platelet adhesion to decellularized tissues was significantly reduced with SLES. Overall, SLES could replace older detergents such as SDS in the decellularization process for generation of transplantable recellularized organs. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3364-3373, 2015. [ABSTRACT FROM AUTHOR]

In eukaryotic cells, mitochondrial dysfunction is associated with a variety of human diseases. Delivery of exogenous functional mitochondria into damaged cells has been proposed as a mechanism of cell transplant and physiological repair for damaged tissue. We here demonstrated that isolated mitochondria can be transferred into homogeneic and xenogeneic cells by simple co-incubation using genetically labelled mitochondria, and elucidated the mechanism and the effect of direct mitochondrial transfer. Intracellular localization of exogenous mitochondria was confirmed by PCR, real-time PCR, live fluorescence imaging, three-dimensional reconstruction imaging, continuous time-lapse microscopic observation, flow cytometric analysis and immunoelectron microscopy. Isolated homogeneic mitochondria were transferred into human uterine endometrial gland-derived mesenchymal cells in a dose-dependent manner. Moreover, mitochondrial transfer rescued the mitochondrial respiratory function and improved the cellular viability in mitochondrial DNA-depleted cells and these effects lasted several days. Finally, we discovered that mitochondrial internalization involves macropinocytosis. In conclusion, these data support direct transfer of exogenous mitochondria as a promising approach for the treatment of various diseases. [ABSTRACT FROM AUTHOR]

In wavelength division multiplexing (WDM) technology, high-speed large-capacity communication is realized by transmitting multiple optical signals with different wavelengths in parallel on an optical fiber. In WDM technology, the logical topology of the network can generally be modified by changing the wavelength assignment to the transmitters and receivers. Thus it is important to develop an algorithm that derives the wavelength assignment that maximizes the transmission efficiency of the network. This paper considers a bidirectional Manhattan street network which has a regular topology, and proposes a hierarchical two-stage heuristic algorithm. In the first stage, the initial solution is derived by hierarchical region division and node assignment to the regions. In the second stage, the solution is improved by simulated annealing (SA). The proposed algorithm is evaluated by simulations of random instances and instances for which optimal solutions are already known. The effectiveness of the proposed algorithm is demonstrated through comparisons to the existing one. © 2007 Wiley Periodicals, Inc. Syst Comp Jpn, 38(4): 74–83, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.10534 [ABSTRACT FROM AUTHOR]