Month: April 2024

Abstract

The prevalence of chronic kidney disease (CKD) is increasing globally, especially in elderly patients. Uremic cardiomyopathy is a common cardiovascular complication of CKD, characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and fibrosis. Kisspeptins and their receptor, KISS1R, exert a pivotal influence on kidney pathophysiology and modulate age-related pathologies across various organ systems. KISS1R agonists, including kisspeptin-13 (KP-13), hold promise as novel therapeutic agents within age-related biological processes and kidney-related disorders. Our investigation aimed to elucidate the impact of KP-13 on the trajectory of CKD and uremic cardiomyopathy. Male Wistar rats (300–350 g) were randomized into four groups: (I) sham-operated, (II) 5/6 nephrectomy-induced CKD, (III) CKD subjected to a low dose of KP-13 (intraperitoneal 13 µg/day), and (IV) CKD treated with a higher KP-13 dose (intraperitoneal 26 µg/day). Treatments were administered daily from week 3 for 10 days. After 13 weeks, KP-13 increased systemic blood pressure, accentuating diastolic dysfunction’s echocardiographic indicators and intensifying CKD-associated markers such as serum urea levels, glomerular hypertrophy, and tubular dilation. Notably, KP-13 did not exacerbate circulatory uremic toxin levels, renal inflammation, or fibrosis markers. In contrast, the higher KP-13 dose correlated with reduced posterior and anterior wall thickness, coupled with diminished cardiomyocyte cross-sectional areas and concurrent elevation of inflammatory (Il6, Tnf), fibrosis (Col1), and apoptosis markers (Bax/Bcl2) relative to the CKD group. In summary, KP-13’s influence on CKD and uremic cardiomyopathy encompassed heightened blood pressure and potentially activated inflammatory and apoptotic pathways in the left ventricle.

Abstract

Skeletal muscle adaptation to external stimuli, such as regeneration following injury and hypertrophy in response to resistance exercise, are blunted with advanced age. The accumulation of senescent cells, along with defects in myogenic progenitor cell (MPC) proliferation, have been strongly linked as contributing factors to age-associated impairment in muscle adaptation. p53 plays an integral role in all these processes, as upregulation of p53 causes apoptosis in senescent cells and prevents mitotic catastrophe in MPCs from old mice. The goal of this study was to determine if a novel pharmaceutical agent (BI01), which functions by upregulating p53 through inhibition of binding to MDM2, the primary p53 regulatory protein, improves muscle regeneration and hypertrophy in old mice. BI01 effectively reduced the number of senescent cells in vitro but had no effect on MPC survival or proliferation at a comparable dose. Following repeated oral gavage with 2 mg/kg of BI01 (OS) or vehicle (OV), old mice (24 months) underwent unilateral BaCl₂ injury in the tibialis anterior (TA) muscle, with PBS injections serving as controls. After 7 days, satellite cell number was higher in the TA of OS compared to OV mice, as was the expression of genes involved in ATP production. By 35 days, old mice treated with BI01 displayed reduced senescent cell burden, enhanced regeneration (higher muscle mass and fiber cross-sectional area) and restoration of muscle function relative to OV mice. To examine the impact of 2 mg/kg BI01 on muscle hypertrophy, the plantaris muscle was subjected to 28 days of mechanical overload (MOV) in OS and OV mice. In response to MOV, OS mice had larger plantaris muscles and muscle fibers than OV mice, particularly type 2b + x fibers, associated with reduced senescent cells. Together our data show that BI01 is an effective senolytic agent that may also augment muscle metabolism to enhance muscle regeneration and hypertrophy in old mice.

Abstract

Using selenium (Se) nanoparticles has received attention in recent years because of their therapeutic benefits due to their anticancer, antioxidant, anti-inflammatory, and anti-diabetic effects. This research was conducted to evaluate the possible protective impact of nano-Se on renal unilateral ischemia/reperfusion injury (uIRI) in adult male Wistar rats. Using clamping of the left renal pedicle within 45 min uIRI was induced. The animals were randomly divided into nine groups of control, nano-Se (0.25, 0.5, and 1 mg/kg bw/day) alone, uIRI control, and uIRI rats administrated with nano-Se. At 30 days after treatment, the animals were sacrificed to be assessed biochemically and histopathologically. Nano-Se in uIRI groups have significantly decreased serum creatinine, urea levels, renal histological damage, and increased antioxidant status. Also, our findings demonstrated that the administration of nano-Se caused a significant decrease in the immunoreactivity level of the epidermal growth factor (EGF) and EGFR expression (EGF receptor) in the renal tissue of the uIRI rats. Therefore, nano-Se possesses renoprotective effects, and this effect might be attributable to its antioxidant and free radical scavenger effects. These renoprotective effects may depend on the decreased EGF immunoreactivity level and EGFR expression in the kidney tissue and improve the structure of the kidney tissue. Thus, our research provided biochemical and histological data supporting the potential clinical use of nano-Se for the treatment of certain kidney disorders.

Abstract

Foreign direct investment (FDI) remains a preferred mode for multinational enterprises to access international markets, resources, and technology. However, there are vigorous debates in the academic literature about the magnitude of inward FDI spillovers and their effect on the economic growth of host countries. In this paper, we argue that these empirical inconsistencies arise from the narrow “home-host” bilateral context in which inward FDI spillovers are analyzed. Further, we show that the inconsistencies can be resolved by adopting a broader, multilateral network perspective to estimate the effects of inward FDI. This perspective allows us to account for the differences in inward FDI spillovers from different investing countries and aggregate these to assess the overall impact of inward FDI. We use quantitative network-centric analysis to model the multilateral connectivity amongst nations engendered by inward FDI. Specifically, we use a panel data set of over 200 host countries spanning two decades to demonstrate that (a) the diversity of inward FDI measured by the number of investing countries and (b) the quality of inward FDI measured by the structural position of investing countries in the global inward FDI network is correlated with higher economic growth of host countries.

Abstract

Status is an important intangible asset, yet when firms enter new countries, they lack standing in new social hierarchies as outsiders. Conventional wisdom suggests embeddedness in host-country networks can alleviate newcomers’ liability of outsidership. We complement this with insights from status signaling theory: Newcomers in host countries can address their liability of outsidership through the visual display of social affiliations. We utilize a novel visual qualitative research approach that analyzes annual report photographs of an emerging-market family business, depicting the firm’s leaders with high-status alters. Complementing the international business literature, which emphasizes strong ties to host-country business partners, we identify three signaling mechanisms that are more circuitous: bypass (host-country affiliations beyond the firm’s industry), allusion (global affiliations beyond the host country and industry, often celebrities), and aspiration (global industry affiliations). We also suggest that such diffuse status signaling mechanisms may be especially salient in emerging-market family firms investing in developed markets, which are accorded low status in many developed markets. These firms feature firm/owner identity overlaps, long leader tenures, and a tendency to build reputation through prosocial behavior, facilitating the activation of status signaling tactics through ephemeral affiliations with high-status actors situated in world society.

Abstract

The crucial role and fragility of global supply chains highlight the need for deeper insights into the factors that can promote the establishment of global supply chain relations. We examine the impact of financial statement comparability on firms’ establishment of global supply chain relations. Using a large sample of supply chain relations from 49 non-U.S. economies over the period 2003–2020, we find that non-U.S. firms are more likely to establish and maintain more supply chain relations with U.S. firms when their financial statements are more comparable to industry peers in the U.S. To address endogeneity concerns, we show that our findings are robust to identification strategies exploring the exogenous changes in financial statement comparability associated with IFRS adoption or PCAOB international inspections. Moreover, we find that the effect of financial statement comparability on cross-border supply chain relations is more pronounced when the information barrier is higher between non-U.S. economies and the U.S. Overall, our study provides new insights into the impact of financial statement comparability on firms’ establishment of cross-border supply chain relations and sheds lights on the role of financial statement comparability in promoting international trade.

Abstract

Salinity control, nutrient additions, and sediment supply were directly or indirectly the rationale for a $220 million coastal wetland restoration project (Davis Pond River Diversion) that began in 2002. We sampled Mississippi River water going in and out of the receiving basin from 1999 to 2018 to understand why wetland loss increased after it began. There was a reduction in inorganic sediments, nitrogen (N), and phosphorus (P) concentrations within the ponding area of 77%, 39% and 34%, respectively, which is similar to that in other wetlands. But the average sediment accumulation of 0.6 mm year⁻¹ inadequately balances the present-day 5.6 mm year⁻¹ sea level rise or the 7.9 ± 0.13 mm year⁻¹ accretion rates in these organic soils. Nutrients added likely reduced live belowground biomass and soil strength, and increased decomposition of the organic matter necessary to sustain elevations. The eutrophication of the downstream aquatic system from the diversion, principally by P additions, increased Chl a concentrations to a category of ‘poor’ water quality. We conclude that this diversion, if continued, will be a negative influence on wetland area and will eutrophy the estuary. It is a case history example for understanding the potential effects arising from proposed river diversions.