scholarly journals Selective HIF stabilization alleviates hepatocellular steatosis and ballooning in a rodent model of 70% liver resection

2021 ◽  
Author(s):  
Samuele Iesari ◽  
Isabelle Leclercq ◽  
Nicolas Joudiou ◽  
Mina Komuta ◽  
Aurélie Daumerie ◽  
...  
Keyword(s):  
Liver Resection ◽  
Liver Function ◽  
Rna Sequencing ◽  
Potential Role ◽  
Successful Outcome ◽  
Cellular Respiration ◽  
Postoperative Phase ◽  
Living Donor Transplantation ◽  
Small For Size

Background: Small-for-size syndrome looms over patients needing liver resection or living-donor transplantation. Hypoxia has been shown to be crucial for the successful outcome of liver resection in the very early postoperative phase. While poorly acceptable as such in real-world clinical practice, hypoxia responses can still be simulated by pharmacologically raising levels of its transducers, the hypoxia-inducible factors (HIF). We aimed to assess the potential role of a selective inhibitor of HIF degradation in 70% hepatectomy (70%Hx). Methods: In a pilot study, we tested the required dose of roxadustat to stabilize liver HIF1α. We then performed 70%Hx in 8-week-old male Lewis rats and administered 25 mg/kg of roxadustat (RXD25) at the end of the procedure. Regeneration was assessed: ki67 and EdU immunofluorescent labeling, and histological parameters. We also assessed liver function via a blood panel and functional gadoxetate-enhanced magnetic resonance imaging, up to 47 hours after the procedure. Metabolic results were analyzed by means of RNA sequencing. Results: Roxadustat effectively increased early HIF1α transactivity. Liver function did not appear to be improved nor liver regeneration to be accelerated by the experimental compound. However, treated livers showed a mitigation in hepatocellular steatosis and ballooning, known markers of cellular stress after liver resection. RNA sequencing confirmed that roxadustat unexpectedly increases lipid breakdown and cellular respiration. Conclusions: Selective HIF stabilization did not result in an enhanced liver function after standard liver resection, but it induced interesting metabolic changes that are worth studying for their possible role in extended liver resections and fatty liver diseases.

scholarly journals An Evidence-Based Multidisciplinary Approach to the Management of Hepatocellular Carcinoma (HCC): The Alberta HCC Algorithm

2010 ◽  
Vol 24 (11) ◽  
pp. 643-650 ◽  
Author(s):  
Kelly W Burak ◽  
Norman M Kneteman
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Liver Function ◽  
Potential Role ◽  
Staging System ◽  
Evidence Based ◽  
Transarterial Radioembolization ◽  
Bclc Staging ◽  
Tumour Characteristics

Hepatocellular carcinoma (HCC) is one of only a few malignancies with an increasing incidence in North America. Because the vast majority of HCCs occur in the setting of a cirrhotic liver, management of this malignancy is best performed in a multidisciplinary group that recognizes the importance of liver function, as well as patient and tumour characteristics. The Barcelona Clinic Liver Cancer (BCLC) staging system is preferred for HCC because it incorporates the tumour characteristics (ie, tumour-node-metastasis stage), the patient’s performance status and liver function according to the Child-Turcotte-Pugh classification, and then links the BCLC stage to recommended therapeutic interventions. However, the BCLC algorithm does not recognize the potential role of radiofrequency ablation for very early stage HCC, the expanding role of liver transplantation in the management of HCC, the role of transarterial chemoembolization in single large tumours, the potential role of transarterial radioembolization with90Yttrium and the limited evidence for using sorafenib in Child-Turcotte-Pugh class B cirrhotic patients. The current review article presents an evidence-based approach to the multidisciplinary management of HCC along with a new algorithm for the management of HCC that incorporates the BCLC staging system and the authors’ local selection criteria for resection, ablative techniques, liver transplantation, transarterial chemoembolization, transarterial radioembolization and sorafenib in Alberta.

scholarly journals Linking Inflammation to Acute Rejection in Small-For-Size Liver Allografts: The Potential Role of Early Macrophage Activation

2004 ◽  
Vol 4 (2) ◽  
pp. 196-209 ◽  
Author(s):  
Zhen-Fan Yang ◽  
David Wing-Yuen Ho ◽  
Andrew Chi-Yuen Chu ◽  
Yan-Qing Wang ◽  
Sheung-Tat Fan
Keyword(s):  
Acute Rejection ◽  
Macrophage Activation ◽  
Potential Role ◽  
Small For Size

scholarly journals New Insights Into the Role of Autophagy in Liver Surgery in the Setting of Metabolic Syndrome and Related Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Ana Isabel Álvarez-Mercado ◽  
Carlos Rojano-Alfonso ◽  
Marc Micó-Carnero ◽  
Albert Caballeria-Casals ◽  
Carmen Peralta ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Liver Resection ◽  
Liver Function ◽  
Liver Surgery ◽  
Metabolic Diseases ◽  
Liver Graft ◽  
Postoperative Results ◽  
Alcoholic Fatty Liver

Visceral obesity is an important component of metabolic syndrome, a cluster of diseases that also includes diabetes and insulin resistance. A combination of these metabolic disorders damages liver function, which manifests as non-alcoholic fatty liver disease (NAFLD). NAFLD is a common cause of abnormal liver function, and numerous studies have established the enormously deleterious role of hepatic steatosis in ischemia-reperfusion (I/R) injury that inevitably occurs in both liver resection and transplantation. Thus, steatotic livers exhibit a higher frequency of post-surgical complications after hepatectomy, and using liver grafts from donors with NAFLD is associated with an increased risk of post-surgical morbidity and mortality in the recipient. Diabetes, another MetS-related metabolic disorder, also worsens hepatic I/R injury, and similar to NAFLD, diabetes is associated with a poor prognosis after liver surgery. Due to the large increase in the prevalence of MetS, NAFLD, and diabetes, their association is frequent in the population and therefore, in patients requiring liver resection and in potential liver graft donors. This scenario requires advancement in therapies to improve postoperative results in patients suffering from metabolic diseases and undergoing liver surgery; and in this sense, the bases for designing therapeutic strategies are in-depth knowledge about the molecular signaling pathways underlying the effects of MetS-related diseases and I/R injury on liver tissue. A common denominator in all these diseases is autophagy. In fact, in the context of obesity, autophagy is profoundly diminished in hepatocytes and alters mitochondrial functions in the liver. In insulin resistance conditions, there is a suppression of autophagy in the liver, which is associated with the accumulation of lipids, being this is a risk factor for NAFLD. Also, oxidative stress occurring in hepatic I/R injury promotes autophagy. The present review aims to shed some light on the role of autophagy in livers undergoing surgery and also suffering from metabolic diseases, which may lead to the discovery of effective therapeutic targets that could be translated from laboratory to clinical practice, to improve postoperative results of liver surgeries when performed in the presence of one or more metabolic diseases.

The potential role of preoperative portal vein embolization for the prevention of small-for-size syndrome

Surgery ◽  
2017 ◽  
Vol 161 (6) ◽  
pp. 1743-1744 ◽  
Author(s):  
Antonios Athanasiou ◽  
Eleftherios Spartalis ◽  
Christos Damaskos ◽  
Demetrios Moris
Keyword(s):  
Portal Vein ◽  
Portal Vein Embolization ◽  
Potential Role ◽  
Small For Size

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

The Effect of Path Length and Display Size on Memory for Spatial Information

2012 ◽  
Vol 59 (3) ◽  
pp. 147-152 ◽  
Author(s):  
Katherine Guérard ◽  
Sébastien Tremblay
Keyword(s):  
Path Length ◽  
Potential Role ◽  
Spatial Information ◽  
Recall Performance ◽  
Minor Role ◽  
Length Effect ◽  
Serial Memory ◽  
Fixed Reference ◽  
A Minor

In serial memory for spatial information, some studies showed that recall performance suffers when the distance between successive locations increases relatively to the size of the display in which they are presented (the path length effect; e.g., Parmentier et al., 2005) but not when distance is increased by enlarging the size of the display (e.g., Smyth & Scholey, 1994). In the present study, we examined the effect of varying the absolute and relative distance between to-be-remembered items on memory for spatial information. We manipulated path length using small (15″) and large (64″) screens within the same design. In two experiments, we showed that distance was disruptive mainly when it is varied relatively to a fixed reference frame, though increasing the size of the display also had a small deleterious effect on recall. The insertion of a retention interval did not influence these effects, suggesting that rehearsal plays a minor role in mediating the effects of distance on serial spatial memory. We discuss the potential role of perceptual organization in light of the pattern of results.

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