A Single Nucleotide Mixture Enhances the Antitumor Activity of Molecular-Targeted Drugs Against Hepatocellular Carcinoma.

New strategies for molecular-targeted drug therapy for advanced hepatocellular carcinoma (HCC) ignore the contribution of the nutritional status of patients and nutritional support to improve physical status and immunity. We aimed to elucidate the role of a single nucleotide mixture (SNM) in the anti-tumor therapy of HCC, and to explore the importance of a SNM as adjuvant therapy for HCC. Compared with a lipid emulsion (commonly used nutritional supplement for HCC patients), the SNM could not induce metabolic abnormalities in HCC cells (Warburg effect), and did not affect expression of metabolic abnormality-related factors in HCC cells.

Polysaccharide extract from Isatidis Radix inhibits multiple inflammasomes activation and alleviate gouty arthritis.

The polysaccharide extract from Isatidis Radix exhibits potent antiinflammatory and antiviral activities, but the mechanism of Isatidis Radix polysaccharide (IRP) remains obscure. Herein, we reported that IRP blocked the activation of nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, leading to the inhibiting of caspase-1 cleavage and IL-1β secretion. Mechanistically, IRP did not inhibit NLRP3 inflammasome through suppressing mitochondrial reactive oxygen species (mtROS) production.

Evodiamine Inhibits Gastric Cancer Cell Proliferation PTEN-Mediated EGF/PI3K Signaling Pathway.

Aims: In this study, the pharmacological effects and potential molecular mechanisms of evodiamine in treating gastric cancer (GC) were investigated.

Methods: GC cells lines of AGS and BGC-823 were treated with evodiamine at various concentrations for different times (24, 48, and 72 h). Inhibition of the proliferation of AGS and BGC-823 cells was assessed using a CCK-8 assay.

Hlf Expression Marks Early Emergence of Hematopoietic Stem Cell Precursors With Adult Repopulating Potential and Fate.

In the aorta-gonad-mesonephros (AGM) region of mouse embryos, pre-hematopoietic stem cells (pre-HSCs) are generated from rare and specialized hemogenic endothelial cells (HECs) endothelial-to-hematopoietic transition, followed by maturation into bona fide hematopoietic stem cells (HSCs). As HECs also generate a lot of hematopoietic progenitors not fated to HSCs, powerful tools that are pre-HSC/HSC-specific become urgently critical. Here, using the gene knockin strategy, we firstly developed an reporter mouse model and detected Hlf-tdTomato expression exclusively in the hematopoietic cells including part of the immunophenotypic CD45 and CD45 pre-HSCs in the embryonic day (E) 10.

Spatiotemporal and Functional Heterogeneity of Hematopoietic Stem Cell-Competent Hemogenic Endothelial Cells in Mouse Embryos.

Hematopoietic stem cells (HSCs) are derived from hemogenic endothelial cells (HECs) during embryogenesis. The HSC-primed HECs increased to the peak at embryonic day (E) 10 and have been efficiently captured by the marker combination CD41CD43CD45CD31CD201KitCD44 (PK44) in the aorta-gonad-mesonephros (AGM) region of mouse embryos most recently. In the present study, we investigated the spatiotemporal and functional heterogeneity of PK44 cells around the time of emergence of HSCs.

Aberrant expression of mA mRNA methylation regulators in colorectal adenoma and adenocarcinoma.

Background: As the most prevalent post-transcriptional mRNA modification in eukaryotes, N6-Methyladenosine (mA) is closely linked to the occurrence and development of colorectal cancer (CRC). However, there is no systematic evaluation of the expression of mA regulatory genes in CRC.

Methods: By analyzing the TCGA database, we identified METTL3, YTHDF1, IGF2BP1, IGF2BP3, EIF3B, HNRNPA2B1 as overexpressed mA regulators in CRC.

Cryptotanshinone specifically suppresses NLRP3 inflammasome activation and protects against inflammasome-mediated diseases.

NLRP3 inflammasome activation is implicated in the pathogenesis of a wide range of inflammatory diseases, but medications targeting the NLRP3 inflammasome are not available for clinical use. Here, we demonstrate that cryptotanshinone (CTS), a major component derived from the traditional medicinal herb Salvia miltiorrhiza Bunge, is a specific inhibitor for the NLRP3 inflammasome. Cryptotanshinone inhibits NLRP3 inflammasome activation in macrophages, but has no effects on AIM2 or NLRC4 inflammasome activation.

Icariside Ⅱ, a main compound in Epimedii Folium, induces idiosyncratic hepatotoxicity by enhancing NLRP3 inflammasome activation.

Idiosyncratic drug-induced liver injury (IDILI) is an infrequent but potentially serious disease that develops the main reason for post-marketing safety warnings and withdrawals of drugs. Epimedii Folium (EF), the widely used herbal medicine, has shown to cause idiosyncratic liver injury, but the underlying mechanisms are poorly understood. Increasing evidence has indicated that most cases of IDILI are immune mediated.

Jinbei Oral Liquid ameliorates bleomycin-induced idiopathic pulmonary fibrosis in rats via reversion of Th1/Th2 shift.

Objective: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal interstitial lung disease with high mortality. The pivotal role of Th1/Th2 immunological balance in the development and progression of IPF has been demonstrated previously. This study aimed to evaluate the effect of Jinbei Oral Liquid (JBOL) on IPF and its relationship with Th1/Th2 shift.

Quantitative examination of the inhibitory activation of molecular targeting agents in hepatocellular carcinoma patient-derived cell invasion via a novel in vivo tumor model.

Background: The outcomes for patients with advanced hepatocellular carcinoma (HCC) receiving sorafenib are far from satisfactory because of treatment resistance to sorafenib. However, the exact mechanism of resistance to sorafenib remains unclear and it is valuable to establish a novel mouse model to quantitatively analyze the inhibition rates of sorafenib on the invasive growth of HCC cells in the liver.

Methods: HCC tissue microblocks derived from patients were cultured and mixed with hydrogel drops.

identification of EP400 and TIA1 as critical transcription factors involved in human hepatocellular carcinoma relapse.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-associated mortality worldwide. Transcription factors (TFs) are crucial proteins that regulate gene expression during cancer progression; however, the roles of TFs in HCC relapse remain unclear. To identify the TFs that drive HCC relapse, the present study constructed co-expression network and identified the Tan module the most relevant to HCC relapse.

Effect of the hyaluronic acid-poloxamer hydrogel on skin-wound healing: in vitro and in vivo studies.

Background: Recent research into skin injury and wound healing has focused mainly on post-trauma hemostasis, infection prevention, dermal regeneration and angiogenesis. However, less attention has been paid to air permeability and moisture loss prevention which also play important roles in injury healing.

Methods: In the present work, we prepared a hyaluronic acid-poloxamer (HA-POL) hydrogel and tested the therapeutic effect of the hydrogel on skin-wound healing.

ETS-1 induces Sorafenib-resistance in hepatocellular carcinoma cells via regulating transcription factor activity of PXR.

Transcription factor E26 transformation specific sequence 1 (ETS-1) is a primary regulator in the metastasis of human cancer cells, especially hepatocellular carcinoma (HCC) cells; and it would affect the prognosis of HCC patients who received chemotherapies. However, the regulatory role of ETS-1 in the resistance of HCC cells to molecular-targeting agent remains poorly understood. In the present work, we demonstrate that high ETS-1 expression correlates with poor prognosis of advanced HCC patients received Sorafenib treatment.

Novel ADAM-17 inhibitor ZLDI-8 enhances the in vitro and in vivo chemotherapeutic effects of Sorafenib on hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the greatest life threats for Chinese people, and the prognosis of this malignancy is poor due to the strong chemotherapy resistance in patients. Notch pathway components mediate cell survival and epithelial-mesenchymal transition (EMT), and also participate in the induction of multi-drug resistance (MDR). In the present study, we demonstrated the discovery of a novel inhibitor for Notch activating/cleaving enzyme ADAM-17, named ZLDI-8; it inhibited the cleavage of NOTCH protein, consequently decreased the expression of pro-survival/anti-apoptosis and EMT related proteins.

[Research progress of Guanxin Danshen formula and its effective components in treating coronary artery heart disease].

Coronary artery heart disease (CHD) is one of the common cardiovascular diseases in clinical. The morbidity and mortality of CHD recently continue increasing in our country, which has aroused wide attention. Many studies confirm that traditional Chinese medicine has better therapeutic effect on CHD.

T cell--associated immunoregulation and antiviral effect of oxymatrine in hydrodynamic injection HBV mouse model.

Although oxymatrine (OMT) has been shown to directly inhibit the replication of hepatitis B virus (HBV) , limited research has been done with this drug . In the present study, the antiviral effect of OMT was investigated in an immunocompetent mouse model of chronic HBV infection. The infection was achieved by tail vein injection of a large volume of DNA solution.

Lower number and decreased function of natural killer cells in hepatitis B virus related acute-on-chronic liver failure.

Background: Hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) refers to acute deterioration occurring in patients with chronic hepatitis B infected liver diseases. An abnormality in NK cells mediated cellular immunity is believed to be a contributing factor. We aimed to evaluate the characteristic of NK cells in the peripheral blood of HBV related ACLF.

Inhibition of Sophocarpine on Poly I: C/D-GalN-Induced Immunological Liver Injury in Mice.

Increasing evidence has suggested that natural killer (NK) cells contribute to the pathogenesis of human immunological liver injury (ILI). Previous studies have demonstrated that Sophocarpine exerts activity in immune modulation. It also has a therapeutic effect on liver protection in that it can alleviate liver fibrosis by suppressing both the activation of hepatic stellate cells and the proliferation of the activated hepatic stellate cells.

Effect of berberine on Escherichia coli, Bacillus subtilis, and their mixtures as determined by isothermal microcalorimetry.

The strong toxicity of pathogenic bacteria has resulted in high levels of morbidity and mortality in the general population. Developing effective antibacterial agents with high efficacy and long activity is in great demand. In this study, the microcalorimetric technique based on heat output of bacterial metabolism was applied to evaluate the effect of berberine on Escherichia coli, Bacillus subtilis, individually and in a mixture of both using a multi-channel microcalorimeter.