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Myocardial ischemia/reperfusion (MI/R) injury, a complicated pathophysiological process, is regulated by lots of signaling pathways. Here in our present study, we identified TANK-binding kinase 1 (TBK1), an IKK-related serine/threonine kinase, as a protective regulator in MI/R injury. Our results indicated that TBK1 was decreased in MI/R injury in mice. However, after overexpressing TBK1 through an intramyocardial injection of TBK1 adenovirus, TBK1 overexpression improved cardiac function detected by echocardiography, decreased infarct size detected by Evans Blue and TTC staining, reduced cardiomyocyte apoptosis measured by TUNEL staining and alleviated disruption of mitochondria and cardiac muscle fibers detected by TEM in response to MI/R injury. Consistently, TBK1 overexpression ameliorated mitochondrial oxygen consumption rate (OCR) in neonatal rat cardiomyocytes (NRCMs) in response to hypoxia/reoxygenation (H/R) injury. Mechanistically, TBK1 overexpression upregulated Bcl-2 (an anti-apoptotic protein) but downregulated Bax (a pro-apoptotic protein) in vivo and in vitro. Collectively, our findings uncovered a pivotal function of TBK1 in MI/R injury through regulating the levels of apoptotic proteins for the first time, which might represent a promising target in treating MI/R patients in the future. • TBK1 overexpression improved the cardiac function, infarct size and cardiomyocyte apoptosis impaired by I/R injury. • TBK1 overexpression improved mitochondrial respiration OCR impaired by H/R injury. • TBK1 alleviated MI/R injury through regulating the levels of apoptotic proteins. [ABSTRACT FROM AUTHOR]

[Display omitted] Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are the most eminent forms of pulmonary involvement in Scleroderma. In this study we investigate the interaction between cytokines and apoptotic proteins in treatment naive Scleroderma (SSc) patients with and without pulmonary involvement. Newly diagnosed treatment naïve Scleroderma (SSc) patients (n = 100) and healthy controls (n = 100) were enrolled. Patients were classified as ILD-SSc, PAH-SSc and non-pulmonary SSc (np-SSc). Study variables like mRSS score, autoantibody profile, serum cytokines, serum TGF-β (1,2,3) and apoptotic proteins were assessed for these patients. Scleroderma patients showed elevated levels of serum cytokines, but significantly lower IL-22 and TGF- β1 when compared to healthy controls (p < 0.05). Apoptotic proteins were significantly elevated among Scleroderma patients, but the patient groups also showed significant lower caspase 1/3/9 levels when compared to healthy controls (p < 0.05). ILD-SSc patients reported higher mRSS score (p = 0.0436) when compared with PAH-SSc and np-SSc. In ILD-SSc patients, finger tightening (p = 0.0481) and calcinosis/lesions (p = 0.0481) were significant clinical presentations whereas, digital ulcers were significantly prominent in np-SSc patients (p = 0.0132). Elevated TGF-β3 levels (p = 0.02) in SSC-ILD and reduced IL-4 levels (p = 0.02) in SSC-PAH were significant cytokines as compared to np-SSc. Significant correlations were obtained among serum cytokines and apoptotic proteins in Scleroderma patients with and without pulmonary involvement. (p < 0.05) Our study highlights the correlation between mRSS score, cytokines and apoptotic proteins in SSc patients with pulmonary involvement. A longitudinal follow up in these patients with assessment of these immunological parameters may be helpful in monitoring the disease. [ABSTRACT FROM AUTHOR]

Abstract: Heart failure is known to be associated with an increase in cardiomyocyte apoptosis; however, neither its occurrence nor the mechanisms involved in hearts failing due to volume overload are completely understood. This study examined some of the signal pathways, which are known to regulate pro- or anti-apoptotic proteins, in heart failure due to volume overload induced by arteriovenous (AV) shunt in male Sprague–Dawley rats. Animals were assessed for cardiac function at 16 weeks of the operation and the left ventricle was used for studying apoptosis and associated signal transduction mechanisms. Hemodynamic and echocardiographic data indicated the presence of severe heart failure in AV shunt rats. A marked elevation in the amount of tumor necrosis factor-α and increased occurrence of apoptosis were detected in the volume overloaded myocardium. Western blot analysis revealed a significant increase in BAX and caspases 3/9 proteins in the failing hearts whereas the levels of phosphorylated Akt and Bcl-2 proteins were decreased. These data suggest that there is a downregulation in the Akt-dependent survival signal involving anti-apoptotic protein, Bcl-2, whereas the signals for the pro-apoptotic protein, BAX, are upregulated and these alterations may play a role in cardiomyocyte apoptosis in heart failure due to volume overload. [Copyright &y& Elsevier]