Differential contributions of G protein- or arrestin subtype-mediated signalling underlie urocortin 3-induced somatostatin secretion in pancreatic δ cells.

Background And Purpose: Pancreatic islets are modulated by cross-talk among different cell types and paracrine signalling plays important roles in maintaining glucose homeostasis. Urocortin 3 (UCN3) secreted by pancreatic β cells activates the CRF receptor (CRFR) and downstream pathways mediated by different G protein or arrestin subtypes in δ cells to cause somatostatin (SST) secretion, and constitutes an important feedback circuit for glucose homeostasis.

Experimental Approach: Here, we used Arrb1, Arrb2, Gs and Gq knockout mice, the G-shRNA-GFP lentivirus, as well as functional assays and pharmacological characterization to study how the coupling of G, G and β-arrestin1 to CRFR contributed to UCN3-induced SST secretion in pancreatic δ cells.

Structure of GPR101-Gs enables identification of ligands with rejuvenating potential.

GPR101 is an orphan G protein-coupled receptor actively participating in energy homeostasis. Here we report the cryo-electron microscopy structure of GPR101 constitutively coupled to Gs heterotrimer, which reveals unique features of GPR101, including the interaction of extracellular loop 2 within the 7TM bundle, a hydrophobic chain packing-mediated activation mechanism and the structural basis of disease-related mutants. Importantly, a side pocket is identified in GPR101 that facilitates in silico screening to identify four small-molecule agonists, including AA-14.

Laparoscopic Double Hepatic Artery Banding/Ligation for Patients With Hepatic Hereditary Haemorrhagic Telangiectasia (HHHT).

Introduction: Hepatic hereditary haemorrhagic telangiectasia (HHHT) is a rare autosomal dominant genetic disease. Some patients may develop cardiac failure, portal hypertension, and biliary ischaemia. To date, there is no standard surgical treatment for HHHT.

circSLC4A7 accelerates stemness and progression of gastric cancer by interacting with HSP90 to activate NOTCH1 signaling pathway.

Gastric cancer stem cells (GCSCs) play critical roles in gastric cancer (GC) initiation and development. Circular RNAs (circRNAs) participate in diverse cancer biological processes and function as tumor suppressors or oncogenes. This study aims to discover the expression profile and functional roles of circRNAs in GCSCs.

subtotal spleen resection combined with selective pericardial devascularization for the treatment of portal hypertension.

Background: Hypersplenism and esophageal varices bleeding are the major complications of portal hypertension (PHT). In recent years, increasing attention has been given to spleen preservation operations. The mode and long-term effects of subtotal splenectomy and selective pericardial devascularization for PHT remain controversial.

NDRG1 facilitates self-renewal of liver cancer stem cells by preventing EpCAM ubiquitination.

Background: Portal vein tumour thrombus (PVTT) is the main pathway of HCC intrahepatic metastasis and is responsible for the poor prognosis of patients with HCC. However, the molecular mechanisms underlying PVTT vascular metastases have not been fully elucidated.

Methods: NDRG1 expression was assessed by immunohistochemistry and immunoblotting in clinical specimens obtained from curative surgery.

Autonomous sensing of the insulin peptide by an olfactory G protein-coupled receptor modulates glucose metabolism.

Along with functionally intact insulin, diabetes-associated insulin peptides are secreted by β cells. By screening the expression and functional characterization of olfactory receptors (ORs) in pancreatic islets, we identified Olfr109 as the receptor that detects insulin peptides. The engagement of one insulin peptide, insB:9-23, with Olfr109 diminished insulin secretion through Gi-cAMP signaling and promoted islet-resident macrophage proliferation through a β cell-macrophage circuit and a β-arrestin-1-mediated CCL2 pathway, as evidenced by β-arrestin-1 mouse models.

Long Noncoding RNA Regulates Expression by Sponging and Promotes Cancer Growth in Hepatocellular Carcinoma.

Objective: The purpose of the study is to explore the potential competing endogenous RNA (ceRNA) network and investigate the molecular mechanism of long noncoding RNA (lncRNA) () in hepatocellular carcinoma (HCC) development.

Methods: By analyzing the data of HCC in The Cancer Genome Atlas (TCGA) database, we included differentially expressed lncRNA and microRNA (miRNA) profiles and constructed ceRNA networks related to the prognosis of HCC patients. qRT-PCR, Western blotting, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), transwell assay, and the nude mouse model were employed to test the effects of and on tumor proliferation and growth and .

Case Report: Incidentally Discovered a Rare Cystic Lesion of Liver: Multicystic Biliary Hamartoma.

Multicystic biliary hamartoma (MCBH) is an extremely rare cystic lesion of the liver. A 37-year old male patient was admitted to our hospital for incidentally discovered hepatic cystic lesions on abdominal ultrasonography. Abdominal contrast-enhanced computed tomography (CT) showed a multilocular cystic lesion in the segment VI, with mild enhancement in the septae and peripheral wall within the lesion.

SHMT2 Overexpression Predicts Poor Prognosis in Intrahepatic Cholangiocarcinoma.

Background And Objective: Serine hydroxymethyltransferase 2 (SHMT2) functions as a key enzyme in serine/glycine biosynthesis and one-carbon metabolism. Recent studies have shown that SHMT2 participated in tumor growth and progression in a variety of cancer types. The objective of the present study is to explore the expression of SHMT2 and evaluate its prognostic value in patients with intrahepatic cholangiocarcinoma (iCCA).

HMGB1 correlates with angiogenesis and poor prognosis of perihilar cholangiocarcinoma via elevating VEGFR2 of vessel endothelium.

Perihilar cholangiocarcinoma (PHCCA) is the most common type of cholangiocarcinoma with low resection rate and high morbidity. The study of PHCCA biomarkers made progresses slowly compared with intrahepatic cholangiocarcinoma because of surgical complexity and low possibility of radical surgery, which resulted in the difficulty of specimen obtainment. To screen and identify new biomarkers in PHCCA, we constructed a retrospective cohort with 121 PHCCA patients and a prospective cohort consisting of 64 PHCCA patients, and screened the candidate biomarkers by immunohistochemistry and quantified PCR.

Sprouty2 suppresses progression and correlates to favourable prognosis of intrahepatic cholangiocarcinoma via antagonizing FGFR2 signalling.

Fibroblast growth factor receptor 2 (FGFR2) was demonstrated to correlate to the progression and prognosis of intrahepatic cholangiocarcinoma (ICC) by numerous evidences. However, as a well-recognized suppressor of FGFR2 signalling, the clinical significance of Sprouty (SPRY) family of ICC has not been investigated. In our study, the expressions of SPRY1-4 in 20 pairs of fresh tumour tissues were detected with qPCR, and in 108 cases of paraffin-embedded tissues with immunohistochemistry.

Ablation of somatostatin cells leads to impaired pancreatic islet function and neonatal death in rodents.

The somatostatin (SST)-secreting cells were mainly distributed in the pancreatic islets, brain, stomach and intestine in mammals and have many physiological functions. In particular, the SST-secreting δ cell is the third most common cell type in the islets of Langerhans. Recent studies have suggested that dysregulation of paracrine interaction between the pancreatic δ cells and β cells results in impaired glucose homeostasis and contributes to diabetes development.

Serine/arginine rich splicing factor 2 expression and clinic pathological features indicating a prognostic factor in human hepatocellular carcinoma patients.

Background: This research was aimed to study the expression of Serine/arginine rich splicing factor 2 (SRSF2) in tissues of hepatocellular carcinoma, and explore the relationship between the expression and the clinic pathological and prognosis of human hepatocellular carcinoma (HCC).

Methods: One hundred and fifty-three pairs HCC tissues and adjacent normal tissue were collected from January 2010 to March 2013. The expression of SRSF2 gene was detected by immunohistochemistry, western blotting and real-time quantitative polymerase chain reaction (PCR), and the relationship between the expression and the clinic pathological and prognosis of HCC being analyzed.

Switching of the substrate specificity of protein tyrosine phosphatase N12 by cyclin-dependent kinase 2 phosphorylation orchestrating 2 oncogenic pathways.

The protein tyrosine phosphatase nonreceptor type 12 (PTPN12) is a multifunctional protein and has elicited much research attention because its decreased protein level has been associated with poor prognosis of several types of cancers. Recently, we have solved the crystal structure of the phosphatase domain of PTPN12, which disclosed a specific PTPN12-insert-loop harboring a cyclin-dependent kinase 2 (CDK2) phosphorylation site. However, the functional significance of this phosphorylation is undefined.

A cullin 4B-RING E3 ligase complex fine-tunes pancreatic δ cell paracrine interactions.

Somatostatin secreted by pancreatic δ cells mediates important paracrine interactions in Langerhans islets, including maintenance of glucose metabolism through the control of reciprocal insulin and glucagon secretion. Disruption of this circuit contributes to the development of diabetes. However, the precise mechanisms that control somatostatin secretion from islets remain elusive.

Prognostic significance of TBL1XR1 in predicting liver metastasis for early stage colorectal cancer.

Background: Liver metastasis is the leading cause of lethal colorectal cancer (CRC). For patients with early stage CRC, metachronous liver metastasis is the primary risk for poor prognosis. Accordingly, identification of prospective biomarkers for metachronous liver metastasis would be invaluable in evaluating patients' clinical outcomes and developing personal treatment therapy.

Correlations between TBL1XR1 and recurrence of colorectal cancer.

More than 25% localized CRC patients died from post-operative metastasis, and risk of metastasis varies among individuals due to the high heterogeneity of CRC. Therefore, figuring out potential biomarkers for disease recurrence would be invaluable to improve the follow-up efficiency and clinical treatment. Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) is a core component of the nuclear receptor corepressor complex, which functions as a repressive coregulatory factor for multiple transcription factors.

TBL1XR1 predicts isolated tumor cells and micrometastasis in patients with TNM stage I/II colorectal cancer.

Background And Aim: A considerable number of early-stage colorectal cancer (CRC) patients may develop cancer relapse or metastasis after curative surgery. Isolated tumor cells (ITC) and micrometastasis in lymph nodes (LNMM), which are undetectable by conventional pathological examination, may be one primary reason. Detection of ITC/LNMM is time-consuming and cost-ineffective; we aimed to find biomarkers in primary CRC tissues to help predicting ITC/LNMM status.

Adaptive Activation of a Stress Response Pathway Improves Learning and Memory Through Gs and β-Arrestin-1-Regulated Lactate Metabolism.

Background: Stress is a conserved physiological response in mammals. Whereas moderate stress strengthens memory to improve reactions to previously experienced difficult situations, too much stress is harmful.

Methods: We used specific β-adrenergic agonists, as well as β-adrenergic receptor (β2AR) and arrestin knockout models, to study the effects of adaptive β2AR activation on cognitive function using Morris water maze and object recognition experiments.

Different downstream signalling of CCK1 receptors regulates distinct functions of CCK in pancreatic beta cells.

Background And Purpose: Cholecystokinin (CCK) is secreted by intestinal I cells and regulates important metabolic functions. In pancreatic islets, CCK controls beta cell functions primarily through CCK1 receptors, but the signalling pathways downstream of these receptors in pancreatic beta cells are not well defined.

Experimental Approach: Apoptosis in pancreatic beta cell apoptosis was evaluated using Hoechst-33342 staining, TUNEL assays and Annexin-V-FITC/PI staining.

[Role of vascular cell adhesion molecule-1 in the mouse model of hepatic ischemia/reperfusion and the hematogenic metastasis].

Objective: To investigate the effect of ischemia/reperfusion (I/R) on tumor metastasis in a experimental mouse model of hematogenous metastasis after I/R and to quantify expression of vascular cell adhesion molecule-1 (VCAM-1) during I/R.

Methods: An experimental mouse model of metastasis after partial hepatic I/R was designed to determine the effects of I/R on tumor metastasis to liver. Tumor loads were valued 14 days after operation.

The catalytic region and PEST domain of PTPN18 distinctly regulate the HER2 phosphorylation and ubiquitination barcodes.

The tyrosine phosphorylation barcode encoded in C-terminus of HER2 and its ubiquitination regulate diverse HER2 functions. PTPN18 was reported as a HER2 phosphatase; however, the exact mechanism by which it defines HER2 signaling is not fully understood. Here, we demonstrate that PTPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination barcodes.

A stress response pathway in mice upregulates somatostatin level and transcription in pancreatic delta cells through Gs and β-arrestin 1.

Aims/hypothesis: Somatostatin secretion from islet delta cells plays an important role in regulating islet function and is tightly controlled by environmental changes. Activation of the adrenergic system promoted somatostatin secretion from islet delta cells; however, the role of the adrenergic system in regulating somatostatin content and transcription has not been defined. An imbalance between the somatostatin content and its secretion may cause dysfunctions in the islet delta cells.