Inhibition of migration and invasion of colorectal cancer cells via deletion of Rac1 with RNA interference

Nucleotides and nucleosides represent an important and ubiquitous class of molecules that interact with specific receptors, regulate a variety of activities within the liver, and play a role in the pathogenesis of hepatic fibrosis. Ecto-nucleotide pyrophosphatase/phosphodiesterases (E-NPPs) are ecto-enzymes that are located on the cell surface. NPP1, NPP2, and NPP3 (abbreviated as NPP1–3 hereafter) have been implicated in the hydrolysis of nucleotides; together with other ecto-nucleotidases, they control the events induced by extracellular nucleotides. We have identified and compared the expression of E-NPP family members in two different phenotypes of the mouse hepatic stellate cell line (GRX). In quiescent-like hepatic stellate cells (HSCs), E-NPP activity was significantly higher, NPP2 mRNA expression decreased and NPP3 mRNA increased. The differential NPP activity and expression in two phenotypes of GRX cells suggests that they are involved in the regulation of extracellular nucleotide metabolism in HSCs. However, the role of E-NPPs in the liver remains to be clarified.     

Prebiotic effects of bovine lactoferrin on specific probiotic bacteria

Bovine lactoferrin (bLf) is a natural iron-binding protein and it has been suggested to be a prebiotic agent, but this finding remains inconclusive. This study explores the prebiotic potential of bLf in 14 probiotics. Initially, bLf (1–32 mg/mL) treatment showed occasional and slight prebiotic activity in several probiotics only during the late experimental period (48, 78 h) at 37 °C. We subsequently supposed that bLf exerts stronger prebiotic effects when probiotic growth has been temperately retarded. Therefore, we incubated the probiotics at different temperatures, namely 37 °C, 28 °C, room temperature (approximately 22–24 °C), and 22 °C, to retard or inhibit their growth. As expected, bLf showed more favorable prebiotic activity in several probiotics when their growth was partially retarded at room temperature. Furthermore, at 22 °C, the growth of Bifidobacterium breve, Lactobacillus coryniformis, L. delbrueckii, L. acidophilus, B. angulatum, B. catenulatum, and L. paraplantarum were completely blocked. Notably, these probiotics started regrowing in the presence of bLf (1–32 mg/mL) in a significant and dose-dependent manner. Accordingly, bLf significantly increased the growth of Pediococcus pentosaceus, L. rhamnosus, and L. paracasei (BCRC 17483; a locally isolated strain) when their growth was retarded by incubation at 22 °C. In conclusion, bLf showed inconsistent prebiotic activity in the 14 probiotics at 37 °C, but revealed strong prebiotic activity in 10 probiotic strains at 22 °C. Therefore, this study enables determining additional roles of Lf in probiotic strains, which can facilitate developing novel combinational approaches by simultaneously using Lf and specific probiotics.     

类囊体腔的酸化与过剩激发能耗散

类囊体腔的酸化可诱导高能态的猝灭。依赖叶黄素循环的能量耗散受到类囊体腔酸化的调控,同时叶黄素循环也可以反馈调控类囊体腔的酸化程度,防止类囊体腔的过度酸化。过度酸化的类囊体腔可导致腔侧一些成分的不稳定,甚至光合器官的破坏,限制蛋白的正常周转,诱导PSⅡ反应中心的失活。     

Spironolactone lowers portal hypertension by inhibiting liver fibrosis, ROCK-2 activity and activating NO/PKG pathway in the bile-duct-ligated rat

Objective

Aldosterone, one of the main peptides in renin angiotensin aldosterone system (RAAS), has been suggested to mediate liver fibrosis and portal hypertension. Spironolactone, an aldosterone antagonist, has beneficial effect on hyperdynamic circulation in clinical practice. However, the mechanisms remain unclear. The present study aimed to investigate the role of spionolactone on liver cirrhosis and portal hypertension.

Methods

Liver cirrhosis was induced by bile duct ligation (BDL). Spironolactone was administered orally (20 mg/kg/d) after bile duct ligation was performed. Liver fibrosis was assessed by histology, Masson''s trichrome staining, and the measurement of hydroxyproline and type I collagen content. The activation of HSC was determined by analysis of alpha smooth muscle actin (α-SMA) expression. Protein expressions and protein phosphorylation were determined by immunohistochemical staining and Western blot analysis, Messenger RNA levels by quantitative real time polymerase chain reaction (Q-PCR). Portal pressure and intrahepatic resistance were examined in vivo.

Results

Treatment with spironolactone significantly lowered portal pressure. This was associated with attenuation of liver fibrosis, intrahepatic resistance and inhibition of HSC activation. In BDL rat liver, spironolactone suppressed up-regulation of proinflammatory cytokines (TNFα and IL-6). Additionally, spironolactone significantly decreased ROCK-2 activity without affecting expression of RhoA and Ras. Moreover, spironolactone markedly increased the levels of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS and the activity of NO effector- protein kinase G (PKG) in the liver.

Conclusion

Spironolactone lowers portal hypertension by improvement of liver fibrosis and inhibition of intrahepatic vasoconstriction via down-regulating ROCK-2 activity and activating NO/PKG pathway. Thus, early spironolactone therapy might be the optional therapy in cirrhosis and portal hypertension.