Exogenous High-Mobility Group Box 1 Protein Injection Improves Cardiac Function after Myocardial Infarction: Involvement of Wnt Signaling Activation

Exogenous high-mobility group box 1 protein (HMGB1) injection could prevent left ventricular remodeling and enhance left ventricular function during myocardial infarction (MI). However, the mechanism remains unclear. This paper was to investigate in the mechanism of cardioprotection of HMGB1 during MI in rats. Anesthetized male rats were treated once with HMGB1 (200 ng) 4 h after MI and then executed after 7 and 28 days, respectively. Cardiac function, collagen deposition, and dishevelled-1 and β-catenin protein expression were measured. After MI 7 days or 28 days, the left ventricular ejection fraction (LVEF) was significantly decreased compared to that of sham-operated control group (P < 0.05). However, the LVEF HMGB1-treated groups were significantly higher compared to those of the MI group in both 7 days and 28 days (P < 0.05). The collagen volume fraction was significantly reduced in the HMGB1-treated group in infarcted border zone. HMGB1 could activate the expression of dishevelled-1 and β-catenin proteins (P < 0.05). Our study suggested that exogenous high-mobility group box 1 protein injection improves cardiac function after MI, which may be involved in Wnt/β-catenin signaling activation

Beta-1-Adrenergic Receptors Mediate Nrf2-HO-1-HMGB1 Axis Regulation to Attenuate Hypoxia/Reoxygenation-Induced Cardiomyocytes Injury in Vitro

Backgroud/Aims: The aim of the study was to evaluate the effects of beta1-adrenergic receptors (β1-ARs) -mediated nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase-1 (HO-1)-high mobility group box 1 protein (HMGB1) axis regulation in hypoxia/reoxygenation (H/R)-induced neonatal rat cardiomyocytes. Methods: The neonatal cultured cardiomyocytes were concentration-dependently pretreated by dobutamine (DOB), a selective β1-adrenergic receptor agonist, in the absence and/or presence of LY294002 (a phosphatidylinositol 3-kinase (PI3K) inhibitor), SB203580 (a p38mitogen-activated-protein kinase (p38MAPK) inhibitor), Nrf2siRNA and HO-1siRNA, respectively, and then treated by H/R. The effects and mechanisms by which H/R-induced cardiomyocytes injury were evaluated. Results: Significant increase of HO-1 was found in neonatal cultured cardiomyocytes treated with DOB, when compared to the control group. Significant change for Nrf2 translocation was also revealed in neonatal cultured cardiomyocytes treated with DOB. Insignificant decreases of NF-kappaB p65 activation and HMGB1 release were observed in H/R-induced neonatal cultured cardiomyocytes treated with DOB, when compared to the control group. Importantly, DOB treatment significantly increased the cell viability and decreased the levels of LDH and MDA in H/R-induced cardiomyocytes injury. However, DOB failed to increase HO-1, inhibit NF-kappaB p65 activation, prevent HMGB1 release and attenuate H/R-induced cardiomyocytes injury when the cultured cardiomyocytes were pretreated by Nrf2siRNA, HO-1siRNA, PI3K inhibitor (LY294002) and p38MAPK inhibitor (SB203580), respectively. Conclusions: β1-ARs-mediated Nrf2-HO-1-HMGB1 axis regulation plays a critical protective role in H/R-induced neonatal rat cardiomyocytes injury in vitro via PI3K/p38MAPK signaling pathway

Exploring the Spatial Heterogeneity of Rural Development in Laos Based on Rural Building Spatial Database

The countryside is the principal area of population agglomeration with a high incidence of global poverty problems. As a shelter for the daily life of rural inhabitants, the rural buildings constitute the element of rural settlements. Moreover, they can directly characterize the level of rural development. Therefore, in the new stage of the Sustainable Development Goals (SDGs), this study selected Laos as the main study area and investigated the effect of different factors on the spatial heterogeneity of rural development based on the rural building spatial database. With the geodetector, the results are summarized as follows: (1) The spatial pattern of rural buildings in different regions of Laos varies significantly, with hot spots areas of rural buildings mainly located in the central and southern regions, while cold spots areas are mainly concentrated in the northern region. (2) Slope, transport infrastructure, and public service are the dominant elements influencing the spatial differentiation of rural buildings in Laos, but spatial heterogeneity existed in different regions of factors. (3) The interaction detector shows that slope ∩ road is the dominant interaction factor influencing the spatial distribution pattern of rural buildings nationwide, and there are marked divergences in the interaction factors. Finally, this study combines the findings to propose corresponding countermeasures for promoting the development and construction of rural areas in Laos

IL-23 Promotes Myocardial I/R Injury by Increasing the Inflammatory Responses and Oxidative Stress Reactions

Background/Aims: Inflammation and oxidative stress play an important role in myocardial ischemia and reperfusion (I/R) injury. We hypothesized that IL-23, a pro-inflammatory cytokine, could promote myocardial I/R injury by increasing the inflammatory response and oxidative stress. Methods: Male Sprague-Dawley rats were randomly assigned into sham operated control (SO) group, ischemia and reperfusion (I/R) group, (IL-23 + I/R) group and (anti-IL-23 + I/R) group. At 4 h after reperfusion, the serum concentration of lactate dehydrogenase (LDH), creatine kinase (CK) and the tissue MDA concentration and SOD activity were measured. The infarcte size was measured by TTC staining. Apoptosis in heart sections were measured by TUNEL staining. The expression of HMGB1 and IL-17A were detected by Western Blotting and the expression of TNF-α and IL-6 were detected by Elisa. Results: After 4 h reperfusion, compared with the I/R group, IL-23 significantly increased the infarct size, the apoptosis of cardiomyocytes and the levels of LDH and CK (all P 0.05). All these effects were abolished by anti-IL-23 administration. Conclusion: The present study suggested that IL-23 may promote myocardial I/R injury by increasing the inflammatory responses and oxidative stress reaction