Prevention and reversal of LV remodeling with neurohormonal inhibitors

Opinion statement Left ventricular (LV) remodeling refers to alterations in ventricular mass, chamber size, and shape that result from myocardial injury, pressure, or volume overload. Numerous studies have demonstrated that LV remodeling correlates with the incidence of heart failure and death, supporting a causative role for remodeling in heart failure progression. Heart failure trials have shown that neurohormonal antagonists, including angiotensin-converting enzyme (ACE) inhibitors and β-adrenergic receptor blockers (β blockers), reduce remodeling in parallel with improved clinical outcomes. Existing data favor using angiotensin II type 1 (AT1) receptor antagonists (or “ARBs”), although their anti-remodeling effects are less well established. Recently, mineralocorticoid receptor antagonists have gained substantial interest based on favorable clinical trial results, although data regarding their effects on remodeling are limited. Thus, an optimal medical regimen to prevent or limit LV remodeling in patients with LV dysfunction should include both an ACE inhibitor and β-adrenergic receptor antagonist, irrespective of the degree of LV dysfunction and symptom status. For patients intolerant to ACE inhibitors, an AT1 receptor antagonist should be substituted. An aldosterone antagonist should be administered to patients with severe, New York Heart Association class III to IV heart failure who have normal or only mildly impaired renal function, or to those patients with depressed LV function following an acute myocardial infarction. Through the aggressive pharmacologic inhibition of both the renin-angiotensin-aldosterone and sympathetic nervous systems, progressive LV remodeling can be prevented or hindered, thereby favorably altering the natural history of the heart failure syndrome.     

Mechanistic insight into the improved Li ion conductivity of solid polymer electrolytes

Polymer based solid electrolytes (SEs) are envisaged as futuristic components of safer solid state energy devices. But the semi-crystalline nature and slow dynamics of the host polymer matrix are found to hamper the ion transport through the solid polymer network and hence solid state devices are still far beyond the scope of practical application. In this study, we unravel the synergistic roles of Li salt (LiClO₄) and two different polymers – polyethylene oxide (PEO) and polydimethyl siloxane (PDMS), in the Li ion transport through their solid blend based electrolyte. A detailed study using dielectric spectroscopy and thermo-mechanical analysis is conducted to understand the tunability of the PEO chain dynamics with LiClO₄ and the mechanism of hopping of Li ions by forming ion pairs with oxygen dipoles on the PEO backbone is established. Despite the lack of PDMS''s capability to solvate ions and promote ion transport directly, its proper mixing within the PEO host matrix is demonstrated to enhance ion transport due to the influence of PDMS on the segmental dynamics of PEO. A detailed molecular dynamics study supported by experimental validation suggests that even inert polymers can affect the dynamics of the active host matrix and increase ion transport, leading to next generation high ionic conductivity solid matrices, and opens new avenues in designing polymer based transparent electrolytes.

The studies shown here prove that both the Li salt and ‘inert-polymer’ mixing have paramount importance in the tunability of Li ion conductivity in solid electrolytes for batteries.     

Digital micromirror device projection printing system for meniscus tissue engineering

Meniscus degeneration due to age or injury can lead to osteoarthritis. Although promising, current cell-based approaches show limited success. Here we present three-dimensional methacrylated gelatin (GelMA) scaffolds patterned via projection stereolithography to emulate the circumferential alignment of cells in native meniscus tissue. Cultured human avascular zone meniscus cells from normal meniscus were seeded on the scaffolds. Cell viability was monitored, and new tissue formation was assessed by gene expression analysis and histology after 2 weeks in serum-free culture with transforming growth factor β1 (10 ng ml^?1). Light, confocal and scanning electron microscopy were used to observe cell–GelMA interactions. Tensile mechanical testing was performed on unseeded, fresh scaffolds and 2-week-old cell-seeded and unseeded scaffolds. 2-week-old cell–GelMA constructs were implanted into surgically created meniscus defects in an explant organ culture model. No cytotoxic effects were observed 3 weeks after implantation, and cells grew and aligned to the patterned GelMA strands. Gene expression profiles and histology indicated promotion of a fibrocartilage-like meniscus phenotype, and scaffold integration with repair tissue was observed in the explant model. We show that micropatterned GelMA scaffolds are non-toxic, produce organized cellular alignment, and promote meniscus-like tissue formation. Prefabrication of GelMA scaffolds with architectures mimicking the meniscus collagen bundle organization shows promise for meniscal repair. Furthermore, the technique presented may be scaled up to repair larger defects.     

颗粒性过敏原对致敏小鼠肥大细胞生成干扰素的影响研究

目的 研究颗粒过敏原诱导过敏性哮喘反应中重要的效应细胞肥大细胞生成干扰素IFN-γ的能力以及可能的作用机制.方法 为模拟环境中附着有过敏原成分的可吸入性颗粒物,将模式过敏原蛋白三硝基苯基结合的卵清蛋白(OVA-TNP)共价偶联于大小均一的微球上形成颗粒状过敏原.肥大细胞首先用识别TNP的IgE致敏,然后用颗粒过敏原进行...