Heart on a chip: Micro-nanofabrication and microfluidics steering the future of cardiac tissue engineering

The evolution of micro and nanofabrication approaches significantly spurred the advancements of cardiac tissue engineering over the last decades. Engineering in the micro and nanoscale allows for the rebuilding of heart tissues using cardiomyocytes. The breakthrough of human induced pluripotent stem cells expanded this field rendering the development of human tissues from adult cells possible, thus avoiding the ethical issues of the usage of embryonic stem cells but also creating patient-specific human engineered tissues. In the case of the heart, the combination of cardiomyocytes derived from human induced pluripotent stem cells and micro/nano engineering devices gave rise to new therapeutic approaches of cardiac diseases. In this review, we survey the micro and nanofabrication methods used for cardiac tissue engineering, ranging from clean room-based patterning (such as photolithography and plasma etching) to electrospinning and additive manufacturing. Subsequently, we report on the main approaches of microfluidics for cardiac culture systems, the so-called “Heart on a Chip”, and we assess their efficacy for future development of cardiac disease modeling and drug screening platforms

Vimentin as a target for the treatment of COVID-19

We and others propose vimentin as a possible cellular target for the treatment of COVID-19. This innovative idea is so recent that it requires further attention and debate. The significant role played by vimentin in virus-induced infection however is well established: (1) vimentin has been reported as a co-receptor and/or attachment site for SARS-CoV; (2) vimentin is involved in viral replication in cells; (3) vimentin plays a fundamental role in both the viral infection and the consequent explosive immune-inflammatory response and (4) a lower vimentin expression is associated with the inhibition of epithelial to mesenchymal transition and fibrosis. Moreover, the absence of vimentin in mice makes them resistant to lung injury. Since vimentin has a twofold role in the disease, not only being involved in the viral infection but also in the associated life-threatening lung inflammation, the use of vimentin-targeted drugs may offer a synergistic advantage as compared with other treatments not targeting vimentin. Consequently, we speculate here that drugs which decrease the expression of vimentin can be used for the treatment of patients with COVID-19 and advise that several Food and Drug Administration-approved drugs be immediately tested in clinical trials against SARS-CoV-2, thus broadening therapeutic options for this type of viral infection

0393: Impact of miR-378* and its target desmin intermediate filament on mitochondria distribution in cardiomyocytes

BackgroundMiR-378 and miR-378* microRNAs are derived from an intron of the PGC-1β gene, a regulator of mitochondrial biogenesis. Their expression is either repressed or increased during heart failure depending on the model. Through proteomics approaches, we previously identified new targets of these miRs in H9c2 fetal cardiomyoblasts, among which lactate dehydrogenase for miR-378 and key cytoskeletal proteins for miR-378*.AimsTo better assess its role in energy metabolism and differentiation; we overexpressed miR-378 and miR-378* in primary neonate rat cardiomyocytes (NRC) that are more differentiated and less proliferative than H9c2 cardiomyoblasts.ResultsWe identified desmin as a new target of miR-378* in NRC. Desmin network plays a key role as a structural integrator of myofibrils and mitochondria positioning. MiR-378* overexpression reduced desmin levels and disrupted its organization. Confocal microscopy analysis of NRC stained with the mitochondrial dye MitoTracker revealed that miR-378* overexpression alters mitochondria distribution in the cell. AAV-mediated rescue of desmin expression in presence of miR-378* preserved mitochondria distribution. Mir-378 overexpression had a milder impact on cell organization than miR-378* and did not directly targetted desmin.Conclusion and perspectivesThese results suggest that changes in miR-378* expression level could play an important role in the coupled alteration of cytoskeletal and mitochondrial networks observed in failing myocardium.Abstract 0393 – Figure: Biological functions regulated by miR-378/378

Coexpression of Myosin Heavy Chain 2b with Myosin Heavy Chain 1- Fact or Artefact?

In skeletal muscle, pure fibres expressing one myosin heavy chain (MyHC) isoform, and intermediate fibres, expressing two and exceptionally three MyHCs have been described. When skeletal muscle adapts its fibre type profile to changed functional demands MyHC isoform transformation follows the pathway: MyHC-1 ↔ MyHC-2a ↔ MyHC-2x/d ↔ MyHC-2b. Therefore, in hybrid fibres only successive isoforms from the proposed pathway should coexist. However, jump fibres in which MyHC-1 is co-expressed with MyHC-2x/d have been described recently. The present study describes possible coexpression of MyHC-1 with MyHC-2b in transforming as well as in normal control mouse and rat muscle fibres. The study is only descriptive and provides not sufficient proof to exclude the possible artefact resulting from unknown technical reasons. Key words: coexpression, mouse, myosin heavy chains, rat

Impaired Skeletal Muscle Repair after Ischemia-Reperfusion Injury in Mice

Ischemia/reperfusion (IR) injury can induce skeletal muscle fibre death and subsequent regeneration. By 14 days, absolute and specific maximal forces and fatigue resistance in ischemic/reperfused soleus muscles were still reduced (−89%, −81%, and −75%, resp.) as compared to control muscles (P < .05). The decrease of these parameters in ischemic/reperfused muscle was much greater than that of myotoxic injured muscles (−12%, −11%, and −19%; P < .05). In addition, at 14 days ischemic/reperfused muscle structure was still abnormal, showing small muscle fibres expressing neonatal myosin heavy chain and large necrotic muscle fibres that were not observed in myotoxin treated muscles. By 56 days, in contrast to myotoxin treated muscles, specific maximal force and muscle weight of the ischemic/reperfused muscles did not fully recover (P < .05). This differential recovery between ischemic/reperfused and myotoxin treated muscles was not related to the differences in the initial cell death, loss of satellite cells after injury, expression of growth factors (IGF1, IGF2..), or capillary density in regenerating muscles. In conclusion, our results demonstrate that IR injury in mice induces long term detrimental effects in skeletal muscles and that the recovery following IR injury was delayed for yet unknown reasons as compared to myotoxic injury

Epo Is Relevant Neither for Microvascular Formation Nor for the New Formation and Maintenance of Mice Skeletal Muscle Fibres in Both Normoxia and Hypoxia

Erythropoietin (Epo) and vascular growth factor (VEGF) are known to be involved in the regulation of cellular activity when oxygen transport is reduced as in anaemia or hypoxic conditions. Because it has been suggested that Epo could play a role in skeletal muscle development, regeneration, and angiogenesis, we aimed to assess Epo deficiency in both normoxia and hypoxia by using an Epo-deficient transgenic mouse model (Epo-TAgh). Histoimmunology, ELISA and real time RT-PCR did not show any muscle fiber atrophy or accumulation of active HIF-1α but an improvement of microvessel network and an upregulation of VEGFR2 mRNA in Epo-deficient gastrocnemius compared with Wild-Type one. In hypoxia, both models exhibit an upregulation of VEGF120 and VEGFR2 mRNA but no accumulation of Epo protein. EpoR mRNA is not up-regulated in both Epo-deficient and hypoxic gastrocnemius. These results suggest that muscle deconditioning observed in patients suffering from renal failure is not due to Epo deficiency

Gonad-related factors promote muscle performance gain during postnatal development in male and female mice

To better define the role of male and female gonad-related factors (MGRF, presumably testosterone, and FGRF, presumably estradiol, respectively) on mouse hindlimb skeletal muscle contractile performance/function gain during postnatal development, we analyzed the effect of castration initiated before puberty in male and female mice. We found that muscle absolute and specific (normalized to muscle weight) maximal forces were decreased in 6-mo-old male and female castrated mice compared with age- and sex-matched intact mice, without alteration in neuromuscular transmission. Moreover, castration decreased absolute and specific maximal powers, another important aspect of muscle performance, in 6-mo-old males, but not in females. Absolute maximal force was similarly reduced by castration in 3-mo-old muscle fiber androgen receptor (AR)-deficient and wild-type male mice, indicating that the effect of MGRF was muscle fiber AR independent. Castration reduced the muscle weight gain in 3-mo mice of both sexes and in 6-mo females but not in males. We also found that bone morphogenetic protein signaling through Smad1/5/9 was not altered by castration in atrophic muscle of 3-mo-old mice of both sexes. Moreover, castration decreased the sexual dimorphism regarding muscle performance. Together, these results demonstrated that in the long term, MGRF and FGRF promote muscle performance gain in mice during postnatal development, independently of muscle growth in males, largely via improving muscle contractile quality (force and power normalized), and that MGFR and FGRF also contribute to sexual dimorphism. However, the mechanisms underlying MGFR and FGRF actions remain to be determined

Influences of hydrogen addition from different dual- fuel modes on engine behaviors

Compression ignition (CI) engines have good performance but more exhaust emissions. Dual fuel (DF) engines have better performance and lower emissions compared to CI mode. Also, the scarcity of fossil fuels made the researchers to find alternative fuels to power CI engines. Therefore, the present work aims to use hydrogen (H2) and honne oil biodiesel (BHO) to investigate the performance of CI engines in DF mode. Also, it aims to compare the performance of CI engines in various DF modes, namely induction, manifold injection, and port injection. First, the CI engine was fuelled completely by diesel fuel and BHO. The data were gathered when the engine ran at a constant engine speed of 1500 rpm and at 80% load. Second, the CI engine was operated in various DF modes and data were generated. CI engine operation in DF mode was smooth with biodiesel and H2. The brake thermal efficiency (BTE) of 32% and 31.1% was reported with diesel and biodiesel, respectively, for manifold injection due to low energy content and high viscosity of biodiesel. These values were higher than CI mode and other DF modes. Fuel substitution percentage for DF manifold injection was 60% and 57% with diesel and biodiesel, respectively. Smoke, hydrocarbon (HC), and carbon monoxide (CO) emissions were lower than conventional mode, but a reverse trend was observed for oxides of nitrogen (NOx) emissions. Heat release rate (HRR) and peak pressure (PP) were higher than conventional mode due to the fast combustion rate of hydrogen. The shortest ignition delay (ID) period was noticed for traditional diesel fuel, but it was longer for BHO biodiesel due to its higher viscosity and lower cetane number. On the contrary, the presence of hydrogen led to an increment in the combustion duration (CD) owing to the scarcity of oxygen in CD. Consequently, the paper clearly showed that the injection way of hydrogen plays a respectable role in the engine characteristics.https://wileyonlinelibrary.com/journal/ese3hj2023Mechanical and Aeronautical Engineerin