Endothelial Tgfbr2 Deficiency Ameliorate Liver Fibrosis Through Regulating Angiocrine Signalling and Macrophage Accumulation.

Background & Aims: Transforming growth factor (TGF)-β signalling plays an indispensable role in promoting the activation of hepatic stellate cells and inducing epithelial-mesenchymal transition of hepatocytes during liver fibrosis. Liver sinusoidal endothelial cells (LSECs) undergo capillarisation and promote inflammatory responses following liver injury. Here, we investigated the role of TGF-β signalling in LSECs during liver fibrosis.

Targeting 5-Hydroxytryptamine Receptor 1A in the Portal Vein to Decrease Portal Hypertension.

Background & Aims: Portal hypertension (PH) is one of the most frequent complications of chronic liver disease. The peripheral 5-hydroxytryptamine (5-HT) level was increased in cirrhotic patients. We aimed to elucidate the function and mechanism of 5-HT receptor 1A (HTR1A) in the portal vein (PV) on PH.

The α-1 Adrenergic Receptor Antagonist Doxazosin Attenuates Liver Fibrosis by Alleviating Sinusoidal Capillarization and Liver Angiogenesis.

Liver fibrosis and cirrhosis, which are caused by chronic liver injury, represent common and intractable clinical challenges of global importance. However, effective therapeutics are lacking. Therefore, the study examines the effect of doxazosin on liver fibrosis.

Depletion of Tgfbr2 in hepatocytes alleviates liver fibrosis and restores hepatic function in fibrotic mice.

Objectives: Previous studies have demonstrated the pivotal role of transforming growth factor (TGF)-β signaling in activating hepatic stellate cells during liver fibrosis. In this study we aimed to demonstrate the effects and underlying mechanism of TGF-β signaling in hepatocytes on hepatic fibrogenesis.

Methods: Hepatocyte-specific Tgfbr2-knockout (Tgfbr2 ) mice were generated by AAV8-TBG-Cre injection via the tail vein of Tgfbr2 mice.

Sulodexide attenuates liver fibrosis in mice by restoration of differentiated liver sinusoidal endothelial cell.

Sulodexide is a heparinoid compound with wide-ranging pharmacological activities. However, the effect of sulodexide on liver fibrogenesis has not been reported. In this study, we aim to evaluate the therapeutic potential of sulodexide in mouse model of liver fibrosis and explore the underlying antifibrotic mechanisms.

Novel therapeutics for portal hypertension and fibrosis in chronic liver disease.

Portal hypertension (PH) is the most common non-neoplastic complication of chronic liver disease, determining clinical complications that lead to death or liver transplantation. PH results from increased resistance to portal blood flow through the cirrhotic liver, which is due to hepatic fibrosis and microcirculatory dysfunction. The present review focuses on the pathophysiology of fibrosis and PH, describes currently used treatments, and critically discusses potential therapeutic options.

Targeting PRMT5 Activity Inhibits the Malignancy of Hepatocellular Carcinoma by Promoting the Transcription of HNF4α.

: Liver cancer stem cells (LCSCs) are responsible for the initiation, progression and chemoresistance of liver cancer. However, no agent targeting LCSC is available in the clinic to date. Here, we investigated the effects of targeting protein arginine methyltransferase 5 (PRMT5), an epigenetic regulator, on LCSCs and HCC using a novel PRMT5 inhibitor DW14800.

FOXA2 suppresses the metastasis of hepatocellular carcinoma partially through matrix metalloproteinase-9 inhibition.

The forkhead box transcription factor A2 (FOXA2) is a member of the hepatocyte nuclear factor family and plays an important role in liver development and metabolic homeostasis, but its role in the metastasis of hepatocellular carcinoma (HCC) has not been evaluated. In this study, we found that the expression of FOXA2 was decreased in 68.1% (49/72) of human HCC tissues compared with their paired non-cancerous adjacent tissues.

The transcription factor FOXA2 suppresses gastric tumorigenesis in vitro and in vivo.

Background And Aims: The transcription factor forkhead box A2 (FOXA2) plays a central role in the development of endoderm-derived organs. It has been reported that FOXA2 acts as a suppressor in many kinds of tumor. However, little is known about the role of FOXA2 in gastric cancer.

Gemcitabine in the chemoradiotherapy for locally advanced pancreatic cancer: a meta-analysis.

Aims: Whether gemcitabine based chemoradiotherapy (GEM-based CRT) is superior to 5-fluorouracil based chemoradiotherapy (5-FU-based CRT) for locally advanced pancreatic cancer (LAPC) remains uncertain. The aim of the present study was to evaluate the effect of GEM-based CRT compared with 5-FU-based CRT.

Methods: Electronic database including Medline, Embase, Cochrane controlled trials register, PubMed (update to December 2010) and manual bibliography searches were carried out.