Design and optimization of novel Tetrahydro-β-carboline-based HDAC inhibitors with potent activities against tumor cell growth and metastasis.

Histone deacetylases (HDACs) are validated drug targets for various therapeutic applications. A series of Tetrahydro-β-carboline-based hydroxamate derivatives, designed as HDAC inhibitors (HDACis), were synthesized. Compound 11g exhibited strong inhibitory activity against HDAC1 and the A549 cancer cell line.

Discovery of a novel hybrid coumarin-hydroxamate conjugate targeting the HDAC1-Sp1-FOSL2 signaling axis for breast cancer therapy.

Background: Breast cancer is one of the most lethal cancers in women. Despite significant advances in the diagnosis and treatment of breast cancer, many patients still succumb to this disease, and thus, novel effective treatments are urgently needed. Natural product coumarin has been broadly investigated since it reveals various biological properties in the medicinal field.

Online soft measurement method for chemical oxygen demand based on CNN-BiLSTM-Attention algorithm.

The measurement of chemical oxygen demand (COD) is very important in the process of sewage treatment. The value of COD reflects the effectiveness and trend of sewage treatment to a certain extent, but obtaining accurate data requires high cost and labor intensity. To1 solve this problem, this paper proposes an online soft measurement method for COD based on Convolutional Neural Network-Bidirectional Long Short-Term Memory Network-Attention Mechanism (CNN-BiLSTM-Attention) algorithm.

Targeting the E2F1/Rb/HDAC1 axis with the small molecule HR488B effectively inhibits colorectal cancer growth.

Colorectal cancer (CRC), the third most common cancer worldwide, remains highly lethal as the disease only becomes symptomatic at an advanced stage. Growing evidence suggests that histone deacetylases (HDACs), a group of epigenetic enzymes overexpressed in precancerous lesions of CRC, may represent promising molecular targets for CRC treatment. Histone deacetylase inhibitors (HDACis) have gradually become powerful anti-cancer agents targeting epigenetic modulation and have been widely used in the clinical treatment of hematologic malignancies, while only few studies on the benefit of HDACis in the treatment of CRC.

Enhanced Feature Extraction Network Based on Acoustic Signal Feature Learning for Bearing Fault Diagnosis.

The method of acoustic radiation signal detection not only enables contactless measurement but also provides comprehensive state information during equipment operation. This paper proposes an enhanced feature extraction network (EFEN) for fault diagnosis of rolling bearings based on acoustic signal feature learning. The EFEN network comprises four main components: the data preprocessing module, the information feature selection module (IFSM), the channel attention mechanism module (CAMM), and the convolutional neural network module (CNNM).

YF343, A Novel Histone Deacetylase Inhibitor, Combined with CQ to Inhibit- Autophagy, Contributes to Increased Apoptosis in Triple- Negative Breast Cancer.

Background: Compounds that target tumor epigenetic events are likely to constitute a prominent strategy for anticancer treatment. Histone deacetylase inhibitors (HDACis) have been developed as prospective candidates in anticancer drug development, and currently, many of them are under clinical investigation. We assessed the anticancer efficacy of a now hydroxamate-based HDACi, YF-343, in triple-negative breast cancer development and studied its potential mechanisms.

Clinical value of urinary retinol-binding protein in ascites due to cirrhosis.

The aim of the present study was to explore the clinical value of urinary retinol-binding protein (RBP) level in the prognosis of cirrhotic ascites by assessment of the RBP levels prior to and following ascites treatment. The levels of urinary RBP, urinary microalbumin (mAlb), serum urea nitrogen (urea) and serum creatinine (Cr), and the estimated glomerular filtration rate (eGFR) were measured in 90 patients with cirrhosis and ascites hospitalized in a single institution between May 2011 and January 2012, and in 30 healthy controls. The levels of urinary mAlb, serum urea and serum Cr were higher in the cirrhotic patients compared with the healthy controls (P<0.

Hemodynamic effects of renin-angiotensin-aldosterone inhibitor and β-blocker combination therapy vs. β-blocker monotherapy for portal hypertension in cirrhosis: A meta-analysis.

β-blockers are commonly used for the treatment of acute variceal bleeding in cirrhosis. Renin-angiotensin-aldosterone antagonists (angiotensin I-converting enzyme inhibitors, angiotensin receptor blockers and aldosterone antagonists) are potential therapies for portal hypertension. Several studies have compared the renin-angiotensin-aldosterone system (RAAS) inhibitor and β-blocker combination therapy vs.

Erratum: Oncogenic role of the Notch pathway in primary liver cancer (Review).

[This corrects the article DOI: 10.3892/ol.2016.

Effects of Omega-3 Fatty Acid in Nonalcoholic Fatty Liver Disease: A Meta-Analysis.

A meta-analysis was conducted to assess the effect of omega-3 fatty acid supplementation (n-3 PUFAs) in lowering liver fat, liver enzyme (alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) levels), and blood lipids (triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL), and low density lipoprotein (LDL)) in patients with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). Methods. MEDLINE/PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, Science Citation Index (ISI Web of Science), Chinese Biomedical Literature Database (CBM), and Chinese National Knowledge Infrastructure (CNKI) were searched for relevant randomized controlled trials on the effects of n-3 polyunsaturated fatty acids (PUFAs) in patients with NAFLD from inception to May 2015.

Oncogenic role of the Notch pathway in primary liver cancer.

Primary liver cancer, which includes hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and fibrolamellar HCC, is one of the most common malignancies and the third leading cause of cancer-associated mortality, worldwide. Despite the development of novel therapies, the prognosis of liver cancer patients remains extremely poor. Thus, investigation of the genetic background and molecular mechanisms underlying the development and progression of this disease has gained significant attention.

A meta-analysis of the diagnostic value of detecting K-ras mutation in pancreatic juice as a molecular marker for pancreatic cancer.

Background: K-ras codon 12 mutation is one of the earliest genetic changes in the development of pancreatic cancer (PC) and accurate detection of K-ras mutations is gaining increasing attention in the field of molecular diagnosis.

Methods: Original research articles which evaluated the diagnostic accuracy of K-ras mutation detection in PC were selected. Data were presented as forest plots and summary receiver operating characteristic curve analysis was used to summarize the overall test performance.

Notch Signaling Coordinates Progenitor Cell-Mediated Biliary Regeneration Following Partial Hepatectomy.

Aberrant transcriptional regulation contributes to the pathogenesis of both congenital and adult forms of liver disease. Although the transcription factor RBPJ is essential for liver morphogenesis and biliary development, its specific function in the differentiation of hepatic progenitor cells (HPC) has not been investigated, and little is known about its role in adult liver regeneration. HPCs are bipotent liver stem cells that can self-replicate and differentiate into hepatocytes or cholangiocytes in vitro.

Inhibitive effects of 15-deoxy-Δ(12),(14)-prostaglandin J2 on hepatoma-cell proliferation through reactive oxygen species-mediated apoptosis.

Objective: 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) induces reactive oxygen species (ROS)-mediated apoptosis in many malignant cells, which has not been studied in hepatoma cells. In this study, we investigated whether 15d-PGJ2 induced apoptosis in hepatocellular carcinoma (HCC) associated with ROS.

Materials And Methods: The LM3, SMMC-7721, and Huh-7 HCC cell lines were treated with 15d-PGJ2 (5-40 μM) for 24, 48, and 72 hours.

A meta-analysis of ursodeoxycholic acid therapy versus combination therapy with corticosteroids for PBC-AIH-overlap syndrome: evidence from 97 monotherapy and 117 combinations.

In this study, a meta-analysis of randomised controlled trials that compared ursodeoxycholic acid (UDCA) monotherapy with therapies combining UDCA and corticosteroids was performed. We found that combination therapy with UDCA and corticosteroids was more effective than UDCA monotherapy for primary biliary cirrhosis-autoimmune hepatitis-overlap syndrome.

Systematic review and meta-analysis: bezafibrate in patients with primary biliary cirrhosis.

Background And Aim: Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cirrhosis (PBC), but not all cases respond well. Evidence has shown that combination therapy of UDCA with bezafibrate significantly improved liver function. A meta-analysis was performed to assess the efficacy and safety of UDCA and bezafibrate combination therapy in the treatment of PBC.

Astaxanthin Inhibits Proliferation and Induces Apoptosis of Human Hepatocellular Carcinoma Cells via Inhibition of Nf-Κb P65 and Wnt/Β-Catenin in Vitro.

Hepatocellular carcinoma (HCC) is a malignant tumor that can cause systemic invasion; however, the exact etiology and molecular mechanism are unknown. Astaxanthin (ASX), a powerful antioxidant, has efficient anti-oxidant, anti-inflammatory, and other activities, and has great research prospects in cancer therapy. We selected the human hepatoma cell lines, LM3 and SMMC-7721, to study the anti-tumor effect and related mechanisms of ASX.

The Protective Effect of Resveratrol on Concanavalin-A-Induced Acute Hepatic Injury in Mice.

Pharmacologic Relevance. Resveratrol, an antioxidant derived from grapes, has been reported to modulate the inflammatory process. In this study, we investigated the effects of resveratrol and its mechanism of protection on concanavalin-A- (ConA-) induced liver injury in mice.

Combination therapy of fenofibrate and ursodeoxycholic acid in patients with primary biliary cirrhosis who respond incompletely to UDCA monotherapy: a meta-analysis.

Background: Although the effectiveness of treatment with ursodeoxycholic acid (UDCA) and fenofibrate for primary biliary cirrhosis (PBC) has been suggested by small trials, a systematic review to summarize the evidence has not yet been carried out.

Methods: A meta-analysis of all long-term randomized controlled trials comparing the combination of UDCA and fenofibrate with UDCA monotherapy was performed via electronic searches.

Results: Six trials, which included 84 patients, were assessed.

Astaxanthin Pretreatment Attenuates Hepatic Ischemia Reperfusion-Induced Apoptosis and Autophagy via the ROS/MAPK Pathway in Mice.

Background: Hepatic ischemia reperfusion (IR) is an important issue in complex liver resection and liver transplantation. The aim of the present study was to determine the protective effect of astaxanthin (ASX), an antioxidant, on hepatic IR injury via the reactive oxygen species/mitogen-activated protein kinase (ROS/MAPK) pathway.

Methods: Mice were randomized into a sham, IR, ASX or IR + ASX group.

By reducing hexokinase 2, resveratrol induces apoptosis in HCC cells addicted to aerobic glycolysis and inhibits tumor growth in mice.

Cancer cells exhibit an altered metabolic phenotype known as the aerobic glycolysis. The expression of HK2 changes the metabolic phenotype of cells to support cancerous growth. In the present study, we investigated the inhibitory effect of resveratrol on HK2 expression and hepatocellular carcinoma (HCC) cell glycolysis.

Protective effects of astaxanthin on ConA-induced autoimmune hepatitis by the JNK/p-JNK pathway-mediated inhibition of autophagy and apoptosis.

Objective: Astaxanthin, a potent antioxidant, exhibits a wide range of biological activities, including antioxidant, atherosclerosis and antitumor activities. However, its effect on concanavalin A (ConA)-induced autoimmune hepatitis remains unclear. The aim of this study was to investigate the protective effects of astaxanthin on ConA-induced hepatitis in mice, and to elucidate the mechanisms of regulation.

Combination therapy of ursodeoxycholic acid and budesonide for PBC-AIH overlap syndrome: a meta-analysis.

In this study, a meta-analysis of randomized controlled trials comparing ursodeoxycholic acid (UDCA) monotherapy with combination therapies utilizing UDCA and budesonide was performed. We found that combination therapy with UDCA and budesonide was more effective than UDCA monotherapy for primary biliary cirrhosis-autoimmune hepatitis overlap syndrome. Moreover, compared to prednisone, budesonide has fewer side effects.