EGFR Inhibition Overcomes Resistance to FGFR4 Inhibition and Potentiates FGFR4 Inhibitor Therapy in Hepatocellular Carcinoma.

Aberrant activation of the FGF19-FGFR4 signaling pathway plays an essential role in the tumorigenesis of hepatocellular carcinoma (HCC). As such, FGFR4 inhibition has emerged as a novel therapeutic option for the treatment of HCC and has shown preliminary efficacy in recent clinical trials for patients exhibiting aberrant FGF19 expression. Resistance to kinase inhibitors is common in oncology, presenting a major challenge in the clinical treatment process.

Development of Practical Teaching Model Based on Intelligent Comprehensive Nursing Practice Platform.

To solve the problems existing in the traditional nursing practice teaching and enhance the training quality of nursing baccalaureate students. This article developed a nursing practice teaching model based on the intelligent information platform by integrating the methods of autonomous learning, inquiry learning, blended learning, and action teaching with constructivism learning theory in an attempt to realize the combination of information technology with experimental teaching in nursing baccalaureate program.

Upregulation of CD11b and CD86 through LSD1 inhibition promotes myeloid differentiation and suppresses cell proliferation in human monocytic leukemia cells.

LSD1 (Lysine Specific Demethylase1)/KDM1A (Lysine Demethylase 1A), a flavin adenine dinucleotide (FAD)-dependent histone H3K4/K9 demethylase, sustains oncogenic potential of leukemia stem cells in primary human leukemia cells. However, the pro-differentiation and anti-proliferation effects of LSD1 inhibition in acute myeloid leukemia (AML) are not yet fully understood. Here, we report that small hairpin RNA (shRNA) mediated LSD1 inhibition causes a remarkable transcriptional activation of myeloid lineage marker genes (CD11b/ITGAM and CD86), reduction of cell proliferation and decrease of clonogenic ability of human AML cells.

Aggressive Posterior Retinopathy of Prematurity in a Premature Male Infant.

A premature male infant was born at 30 weeks' gestation with a birth weight of 1,700 g in a rural hospital. He was diagnosed with respiratory distress syndrome and received continuous positive airway pressure treatment for 26 days. At 26 days after birth, the patient was transferred to our hospital for further evaluation and management.

Accuracy of transient elastography in the assessment of chronic hepatitis C-related liver cirrhosis.

Purpose: Staging liver cirrhosis is essential for the management of chronic hepatitis C (CHC). The current meta-analysis evaluated the accuracy of transient elastography for detecting liver cirrhosis in patients with CHC.

Methods: Either prospective or retrospective studies, including cohort and cross sectional studies, in patients diagnosed with chronic hepatitis C, as assessed by transient elastography, were searched from Medline, Cochrane, EMBASE, and Google Scholar databases until March 3, 2015, using the terms "transient elastography, chronic hepatitis C and liver cirrhosis".

Novel matrine derivative MD-1 attenuates hepatic fibrosis by inhibiting EGFR activation of hepatic stellate cells.

Matrine (MT), the effective component of Sophora flavescens Ait, has been shown to have anti-inflammation, immune-suppressive, anti-tumor, and anti-hepatic fibrosis activities. However, the pharmacological effects of MT still need to be strengthened due to its relatively low efficacy and short half-life. In the present study, we report a more effective thio derivative of MT, MD-1, and its inhibitory effects on the activation of hepatic stellate cells (HSCs) in both cell culture and animal models.

Histone methyltransferase SETDB1 regulates liver cancer cell growth through methylation of p53.

SETDB1 is a histone H3K9 methyltransferase that has a critical role in early development. It is located within a melanoma susceptibility locus and facilitates melanoma formation. However, the mechanism by which SETDB1 regulates tumorigenesis remains unknown.

E3 ubiquitin ligase Cbl-b suppresses proallergic T cell development and allergic airway inflammation.

E3 ubiquitin ligase Cbl-b has emerged as a gatekeeper that controls the activation threshold of the T cell antigen receptor and maintains the balance between tolerance and autoimmunity. Here, we report that the loss of Cbl-b facilitates T helper 2 (Th2) and Th9 cell differentiation in vitro. In a mouse model of asthma, the absence of Cbl-b results in severe airway inflammation and stronger Th2 and Th9 responses.

E3 ubiquitin ligase Cbl-b regulates Pten via Nedd4 in T cells independently of its ubiquitin ligase activity.

E3 ubiquitin ligase Cbl-b plays a crucial role in T cell activation and tolerance induction. However, the molecular mechanism by which Cbl-b inhibits T cell activation remains unclear. Here, we report that Cbl-b does not inhibit PI3K but rather suppresses TCR/CD28-induced inactivation of Pten.

Program death-1 regulates peripheral T cell tolerance via an anergy-independent mechanism.

Program death-1 (PD-1) has been documented to negatively regulate immune responses. However, the cellular and molecular mechanisms for PD-1-mediated immune suppression have not been fully elucidated. In this study, we show that loss of PD-1 does not lead to defective induction of CD4(+) T cell anergy in vitro and in vivo.

Syk mediates BCR- and CD40-signaling integration during B cell activation.

CD40 is essential for optimal B cell activation. It has been shown that CD40 stimulation can augment BCR-induced B cell responses, but the molecular mechanism(s) by which CD40 regulates BCR signaling is poorly understood. In this report, we attempted to characterize the signaling synergy between BCR- and CD40-mediated pathways during B cell activation.

TCR-induced Akt serine 473 phosphorylation is regulated by protein kinase C-alpha.

Akt signaling plays a central role in T cell functions, such as proliferation, apoptosis, and regulatory T cell development. Phosphorylation at Ser(473) in the hydrophobic motif, along with Thr(308) in its activation loop, is considered necessary for Akt function. It is widely accepted that phosphoinositide-dependent kinase 1 (PDK-1) phosphorylates Akt at Thr(308), but the kinase(s) responsible for phosphorylating Akt at Ser(473) (PDK-2) remains elusive.

Cutting edge: CTLA-4--B7 interaction suppresses Th17 cell differentiation.

Th cells that produce IL-17 (Th17 cells) are a distinct subset of Th cells implicated in several autoimmune diseases. Although CD28-B7 interaction has been shown to be involved in Th17 differentiation in vitro, the role of CTLA-4 in controlling Th17 development is completely unknown. We report in this paper that blocking the CTLA-4-B7 interaction potentiates Th17 cell differentiation in vitro and in vivo.

T-cell receptor-induced NF-kappaB activation is negatively regulated by E3 ubiquitin ligase Cbl-b.

It has previously been shown that E3 ubiquitin ligase Casitas B-lineage lymphoma-b (Cbl-b) negatively regulates T-cell activation, but the molecular mechanism(s) underlying this inhibition is not completely defined. In this study, we report that the loss of Cbl-b selectively results in aberrant activation of NF-kappaB upon T-cell antigen receptor (TCR) ligation, which is mediated by phosphatidylinositol 3-kinase (PI3-K)/Akt and protein kinase C-theta (PKC-theta). TCR-induced hyperactivation of Akt in the absence of Cbl-b may potentiate the formation of caspase recruitment domain-containing membrane-associated guanylate kinase protein 1 (CARMA1)-B-cell lymphoma/leukemia 10 (Bcl10)-mucosa-associated lymphatic tissue 1(MALT1) (CBM) complex, which appears to be independent of PKC-theta.

Negative regulation of CD40-mediated B cell responses by E3 ubiquitin ligase Casitas-B-lineage lymphoma protein-B.

It has been documented that CD40 is essential for B cell function. Casitas-B-lineage lymphoma protein-b (Cbl-b), an adapter protein and ubiquitin ligase, has been shown to regulate the activation of T and B cells through their Ag receptors. In this study, we report that CD40-induced B cell proliferation is significantly augmented in mice lacking Cbl-b.