Feed efficiency and the liver proteome of fattening lambs are modified by feed restriction during the suckling period

The present study was designed to describe the effects of early feed restriction of Merino lambs on feed efficiency during the fattening period by examining ruminal microbiota and fermentation parameters, gastrointestinal morphology, digestibility or liver proteome. In total, 24 male Merino lambs were randomly assigned to two experimental treatments (n=12 per treatment). Lambs of the first group (ad libitum (ADL)) were kept permanently with the dams, whereas the other 12 lambs (restricted (RES)) were milk restricted. When lambs reached a live BW (LBW) of 15 kg, all the animals were offered the same complete pelleted diet (35 g dry matter/kg LBW per day) until slaughter at a LBW of 27 kg. The RES lambs showed poorer feed efficiency during the fattening period when compared with the ADL group (feed to gain ratio, 3.69 v. 3.05, P<0.001). No differences were observed in ruminal microbiota, fermentation parameters or apparent digestibility. However, the proportion of the small intestine and the length of ileal villi were reduced in the RES lambs. In total, 26 spots/proteins were identified in the liver proteomic profile, with significant differences (P<0.05) between experimental treatments, suggesting a higher catabolism of proteins and a reduction in β-oxidation of fatty acids in RES lambs when compared with the ADL animals. In conclusion, early feed restriction of Merino lambs during the suckling period promotes long-term effects on the small intestine and the proteomic profile of the liver, which may influence the metabolic use of nutrients, thus negatively affecting feed efficiency during the fattening phase.     

TACE结合立体定向体部X-刀治疗肝癌的临床疗效研究

目的:探讨经肝动脉化疗栓塞(transarterial chemoembolization,TACE)结合立体定向体部X-刀治疗肝癌的临床疗效和安全性。方法:选取2015年12月至2017年8月在我院接受治疗的原发性肝癌患者120例,并将其随机分为X-刀组、TACE组以及联合组,每组患者各40例。X-刀组患者给予单纯X-刀治疗,TACE组给予单纯TACE治疗,联合组给予X-刀联合TACE治疗。观察并比较三组患者临床疗效、生存期、治疗前后肝功能的变化及治疗过程中毒副反应的发生情况情况。结果:联合组患者临床总有效率为47.5%,明显高于X-刀组和TACE组(P0.05);X-刀组患者临床总有效率为27.5%,显著高于TACE组(P0.05)。X-刀组、TACE组、联合组患者生存时间分别为0.73±0.18年、0.48±0.18年、1.10±0.22年,联合组患者生存时间显著长于X-刀组和TACE组(P0.05),X-刀组患者生存时间长于TACE组(P0.05)。三组患者治疗后血清血清谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)、γ-谷胺酰转肽酶(Gamma-glutamyl transpeptidase,γ-GT)、总胆红素(total bilirubin,TBil水平与本组治疗前比较均显著降低(P0.05);联合组患者治疗后血清ALT、AST水平与TACE组和X-刀组比较差异均无统计学意义(P0.05),而血清γ-GT、TBil水平均显著低于TACE组和X-刀组(P0.05)。三组患者毒副反应情况比较差异无统计学意义(P0.05)。结论:TACE结合立体定向体部X-刀治疗肝癌的临床疗效明显优于单用TACE或X-刀治疗,且三种治疗方法的安全性相当。     

A Single Administration of CRISPR/Cas9 Lipid Nanoparticles Achieves Robust and Persistent In Vivo Genome Editing

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Assessment of hepatoprotective potential of Radix Fici Hirtae on alcohol-induced liver injury in Kunming mice

ObjectiveThe objective of the present study was to investigate the hepatoprotective role of Radix Fici Hirtae on acute alcohol-induced liver injury in mice.MethodsThe component of Radix Fici Hirtae was extracted using petroleum ether, chloroform, ethyl acetate and n-butanol and divided into three dose groups of high, medium and low according to the clinical man's normal dose of the 50 g crude drug/d (0.83 g/kg body weight). Saline in concentration of 10 mg/mL, 5 mg/mL and 2.5 mg/mL and a dose of mouse lavage (0.2 mL/10 g mouse body weight) were added to the solution. Histopathlogical analysis of liver was performed. Finally, liver protection was validated by examining the effect of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AKP), and lactate dehydrogenase (LDH) on the hepatic function of mice in alcohol-induced liver injury model.ResultsExcept for group with saturated n-butyl alcohol, for the rest of the groups, pathological changes of hepatic lipid and inflammatory cells infiltration were alleviated and liver sinus was normal. As compared to model group, the concentrations of AST, ALT, AKP and LDH in chloroform groups and ethyl acetate groups were significantly decreased.ConclusionsExtracts of Radix Fici Hirtae are effective for the prevention of alcohol-induced hepatic damage in mice. The results revealed that extracts of Radix Fici Hirtae could be used as hepatoprotective agent.     

Inside Back Cover: Multiphoton dynamic imaging of the effect of chronic hepatic diseases on hepatobiliary metabolism in vivo (J. Biophotonics 9/2018)

In vivo multiphoton imaging was used to map changes in hepatobiliary metabolism in liver fibrosis (left column) and hepatocellular carcinoma (right column). The top row shows the maps of kinetic rate constant of the uptake and esterase processing while the bottom row shows that of bile canalicular excretion of xenobiotics. Further details can be found in the article by Chih‐Ju Lin, Sheng‐Lin Lee, Wei‐Hsiang Wang, et al. ( e201700338 ).

     

Dynamic L-type CaV1.2 channel trafficking facilitates CaV1.2 clustering and cooperative gating

L-type Ca_V1.2 channels are key regulators of gene expression, cell excitability and muscle contraction. Ca_V1.2 channels organize in clusters throughout the plasma membrane. This channel organization has been suggested to contribute to the concerted activation of adjacent Ca_V1.2 channels (e.g. cooperative gating). Here, we tested the hypothesis that dynamic intracellular and perimembrane trafficking of Ca_V1.2 channels is critical for formation and dissolution of functional channel clusters mediating cooperative gating. We found that Ca_V1.2 moves in vesicular structures of circular and tubular shape with diverse intracellular and submembrane trafficking patterns. Both microtubules and actin filaments are required for dynamic movement of Ca_V1.2 vesicles. These vesicles undergo constitutive homotypic fusion and fission events that sustain Ca_V1.2 clustering, channel activity and cooperative gating. Our study suggests that Ca_V1.2 clusters and activity can be modulated by diverse and unique intracellular and perimembrane vesicular dynamics to fine-tune Ca²⁺ signals.     

Inactivation of glycogen synthase kinase 3β (GSK-3β) enhances mitochondrial biogenesis during myogenesis

Background

Mitochondrial biogenesis is crucial for myogenic differentiation and regeneration of skeletal muscle tissue and is tightly controlled by the peroxisome proliferator-activated receptor-γ co-activator 1 (PGC-1) signaling network. In the present study, we hypothesized that inactivation of glycogen synthase kinase (GSK)-3β, previously suggested to interfere with PGC-1 in non-muscle cells, potentiates PGC-1 signaling and the development of mitochondrial biogenesis during myogenesis, ultimately resulting in an enhanced myotube oxidative capacity.

Pathogenesis of biliary fibrosis

Chronic cholestatic liver diseases such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are associated with active hepatic fibrogenesis, and, ultimately, to the development of cirrhosis. However, the precise relationship between cholestasis, in its broad meaning, and liver tissue fibrosis is still poorly defined. Fibrogenesis is currently viewed as a dynamic process that appears strictly related to the extent and duration of parenchymal injury. This relationship is clearly evident in the presence of reiterative hepatocellular necrosis due to viral infection or alcohol abuse. It appears that “pure” intralobular intrahepatic cholestasis secondary to biliary secretory failure of the hepatocyte, in absence of hepatocellular damage, lobular inflammation and bile duct damage and/or proliferation, is not associated with marked and/or progressive liver tissue fibrosis. In contrast, marked and progressive liver tissue fibrosis always follows liver diseases characterized by chronic inflammatory bile duct damage as seen in PBC and PSC or chronic mechanical obstruction of the biliary tree. Overall, the fibrogenic process in these clinical conditions appears to be related to a more complex interaction between immune/inflammatory mechanisms, cytokine networks and the derangement of the homeostasis between epithelial and mesenchymal cells. The elucidation of these mechanisms is indeed crucial for the identification of potential diagnostic and therapeutic targets.     

Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression

Background and aims

Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangiocyte proliferation. Here, the role of bile acid receptors FXR and TGR5 in CCA progression was evaluated.