We have recently reported that tumour necrosis factor-α (TNF-α) increases oxidative stress and apoptosis in cardiomyocytes by upregulating p38 mitogen-activated protein (MAP) kinase (MAPK) phosphorylation. Interleukin-10 (IL-10) blocked these effects of TNF-α by upregulating extracellular signal-regulated kinase 1/2 (ERK 1/2) MAPK phosphorylation. However, the precise site of this IL-10 action is still unknown, and this is investigated in the present study. Cardiomyocytes isolated from adult Sprague–Dawley rats were exposed to TNF-α (10 ng/mL), IL-10 (10 ng/mL), and IL-10+TNF-α (ratio 1) for 4 h. Hydrogen peroxide and antioxidant trolox were used as positive controls. Exposure to TNF-α resulted in an increase in the production of reactive oxygen species, the number of apoptotic cells, caspase-3 activation, and poly-ADP ribose polymerase (PARP) cleavage. Increased oxidative stress by using hydrogen peroxide also caused apoptosis. The changes due to TNF-α were associated with an increase in the inhibitor of κB kinase (IKK) and nuclear factor kappa-B (NFκB) phosphorylation. IL-10 by itself had no effect, but it prevented the above mentioned TNF-α-induced changes. Trolox also mitigated TNF-α induced changes. Pre-exposure of cells to an IKK inhibitor (PS-1145) prevented TNF-α-induced caspase-3 and PARP cleavage. Inhibition of ERK 1/2 MAPK with PD98059 attenuated the protective role of IL-10 against TNF-α-induced activation of IKK and NFκB as well as cardiomyocyte apoptosis. The present study shows that TNF-α-induced activation of the NFκB pathway plays a critical role in cardiomyocyte apoptosis. IL-10 prevents TNF-α-induced NFκB activation and pro-apoptotic changes in cardiomyocytes by inhibiting IKK phosphorylation through the activation of ERK 1/2 MAPK.

Oxidative stress and inflammation are each implicated independently in the development and progression of heart failure. Their interaction, however, is also evident throughout the process from initial injury to cardiac remodeling and failure. In the failing heart, the linkage between excessive reactive oxygen species (ROS) and the cytokine elaboration is manifested in shared elements and cross-promotion within downstream signaling pathways. In spite of this, the failure of anticytokine immunotherapy and antioxidant therapy, which had previously shown promise, suggests that a more complete perspective of ROS-cytokine interaction is required. The present review focuses on two of the major cytokines that are demonstrably connected to oxidative stress--the pro-inflammatory tumor necrosis factor-alpha (TNF-alpha) and the anti-inflammatory interleukin-10 (IL-10)--and their interactions in cardiac remodeling and failure. It is proposed that an optimal balance between TNF-alpha and IL-10 may be of crucial importance in mitigating both inflammation and oxidative stress processes leading to heart failure.

Abnormal conduction and improper electrical impulse propagation are common in heart after myocardial infarction (MI). The scar tissue is non-conductive therefore the electrical communication between adjacent cardiomyocytes is disrupted. In the current study, we synthesized and characterized a conductive biodegradable scaffold by incorporating graphene oxide gold nanosheets (GO-Au) into a clinically approved natural polymer chitosan (CS). Inclusion of GO-Au nanosheets in CS scaffold displayed two fold increase in electrical conductivity. The scaffold exhibited excellent porous architecture with desired swelling and controlled degradation properties. It also supported cell attachment and growth with no signs of discrete cytotoxicity. In a rat model of MI, in vivo as well as in isolated heart, the scaffold after 5 weeks of implantation showed a significant improvement in QRS interval which was associated with enhanced conduction velocity and contractility in the infarct zone by increasing connexin 43 levels. These results corroborate that implantation of novel conductive polymeric scaffold in the infarcted heart improved the cardiac contractility and restored ventricular function. Therefore, our approach may be useful in planning future strategies to construct clinically relevant conductive polymer patches for cardiac patients with conduction defects.

It is known that TNF-α increases the production of ROS and decreases antioxidant enzymes, resulting in an increase in oxidative stress. IL-10 appears to modulate these effects. The present study investigated the role of p38 and ERK1/2 MAPKs in mediating the interplay of TNF-α and IL-10 in regulating oxidative stress and cardiac myocyte apoptosis in Sprague-Dawley male rats. Isolated adult cardiac myocytes were exposed to TNF-α (10 ng/ml), IL-10 (10 ng/ml), and IL-10 + TNF-α ( ratio 1) for 4 h. H₂O₂(100 μM) as a positive control and the antioxidant Trolox (20 μmol/l) were used to confirm the involvement of oxidative stress. H₂O₂treatment increased oxidative stress and apoptosis; TNF-α mimicked these effects. Exposure to TNF-α significantly increased ROS production, caused cell injury, and increased the number of apoptotic cells and Bax-to-Bcl-xl ratio. This change was associated with an increase in the phospho-p38 MAPK-to-total p38 MAPK ratio and a decrease in the phospho-ERK1/2-to-total ERK1/2 ratio. IL-10 treatment by itself had no effect on these parameters, but it prevented the above-listed changes caused by TNF-α. The antioxidant Trolox modulated TNF-α-induced changes in Bax/Bcl-xl, cell injury, and MAPKs. Preexposure of cells to the p38 MAPK inhibitor SB-203580 prevented TNF-α-induced changes. Inhibition of the ERK pathway with PD-98059 attenuated the protective role of IL-10 against TNF-α-induced apoptosis. This study provides evidence in support of the essential role of p38 and ERK1/2 MAPKs in the interactive role of TNF-α and IL-10 in cardiac myocyte apoptosis.

The application of nontoxic 2D transition‐metal carbides (MXenes) has recently gained ground in bioelectronics. In group‐4 transition metals, tantalum possesses enhanced biological and physical properties compared to other MXene counterparts. However, the application of tantalum carbide for bioelectrodes has not yet been explored. Here, fluorine‐free exfoliation and functionalization of tantalum carbide MAX‐phase to synthesize a novel Ta₄C₃T_x MXene‐tantalum oxide (TTO) hybrid structure through an innovative, facile, and inexpensive protocol is demonstrated. Additionally, the application of TTO composite as an efficient biocompatible material for supercapacitor electrodes is reported. The TTO electrode displays long‐term stability over 10 000 cycles with capacitance retention of over 90% and volumetric capacitance of 447 F cm⁻³ (194 F g⁻¹) at 1 mV s⁻¹. Furthermore, TTO shows excellent biocompatibility with human‐induced pluripotent stem cells‐derived cardiomyocytes, neural progenitor cells, fibroblasts, and mesenchymal stem cells. More importantly, the electrochemical data show that TTO outperforms most of the previously reported biomaterials‐based supercapacitors in terms of gravimetric/volumetric energy and power densities. Therefore, TTO hybrid structure may open a gateway as a bioelectrode material with high energy‐storage performance for size‐sensitive applications.