Short-term lipopolysaccharide treatment leads to astrocyte activation in LRRK2 G2019S knock-in mice without loss of dopaminergic neurons.

Background: The G2019S mutation of LRRK2, which enhances kinase activity of the protein, confers a substantial risk of developing Parkinson's disease (PD). However, the mutation demonstrates incomplete penetrance, suggesting the involvement of other genetic or environmental modulating factors. Here, we investigated whether LRRK2 G2019S knock-in (KI) mice treated with the inflammogen lipopolysaccharide (LPS) could model LRRK2 PD.

Nrf2, A Target for Precision Oncology in Cancer Prognosis and Treatment.

Activating nuclear factor-erythroid 2-related factor (Nrf2), a master regulator of redox homeostasis, has been shown to suppress initiation of carcinogenesis in normal cells. However, this transcription factor has recently been reported to promote proliferation of some transformed or cancerous cells. In tumor cells, Nrf2 is prone to mutations that result in stabilization and concurrent accumulation of its protein product.

Overactivated NRF2 induces pseudohypoxia in hepatocellular carcinoma by stabilizing HIF-1α.

Hypoxia-inducible factor-1α (HIF-1α) is highly expressed/activated in most hypoxic tumors including hepatocellular carcinoma (HCC). Another key transcription factor, nuclear factor erythroid 2-related factor 2 (NRF2), is also constitutively overactivated in HCC. In an attempt to determine whether HIF-1α and NRF2 could play complementary roles in HCC growth and progression, we investigated the crosstalk between these two transcription factors and underlying molecular mechanisms in cultured HCC cells and experimentally induced hepatocarcinogenesis as well as clinical settings.

Nrf2 Mutagenic Activation Drives Hepatocarcinogenesis.

Nrf2, a master regulator of oxidative stress, is considered a prominent target for prevention of hepatocellular carcinoma (HCC), one of the leading causes of cancer-related deaths worldwide. Here we report that -deficient mice resisted diethylnitrosamine (DEN)-induced hepatocarcinogenesis without affecting P450-mediated metabolic activation of DEN. Nrf2 expression, nuclear translocation, and transcriptional activity were enhanced in liver tumors.

15-Deoxy-Δ-Prostaglandin J Exerts Proresolving Effects Through Nuclear Factor E2-Related Factor 2-Induced Expression of CD36 and Heme Oxygenase-1.

Aims: 15-Deoxy-Δ-prostaglandin J (15d-PGJ) has been shown to rescue cells from inflammatory insults and to participate in the resolution of acute inflammation. In this study, we investigated molecular mechanisms underlying proresolving effects of 15d-PGJ.

Results: 15d-PGJ injected into the peritoneum of mice facilitated the resolution of zymosan A-induced peritonitis.

Helicobacter pylori Activates IL-6-STAT3 Signaling in Human Gastric Cancer Cells: Potential Roles for Reactive Oxygen Species.

Background: Recent studies have shown that Helicobacter pylori (H. pylori) activates signal transducer and activator of transcription 3 (STAT3) that plays an important role in gastric carcinogenesis. However, the molecular mechanism underlying H.

Helicobacter pylori induces Snail expression through ROS-mediated activation of Erk and inactivation of GSK-3β in human gastric cancer cells.

Helicobacter pylori (H. pylori) infection has been known to be implicated in human gastric carcinogenesis. Snail, the zinc-finger transcription factor known as a key inducer of changes in the cell shape and morphogenetic movement, is aberrantly overexpressed and correlates with lymph node metastasis in gastric cancer.

Peptidyl Prolyl Isomerase PIN1 Directly Binds to and Stabilizes Hypoxia-Inducible Factor-1α.

Peptidyl prolyl isomerase (PIN1) regulates the functional activity of a subset of phosphoproteins through binding to phosphorylated Ser/Thr-Pro motifs and subsequently isomerization of the phosphorylated bonds. Interestingly, PIN1 is overexpressed in many types of malignancies including breast, prostate, lung and colon cancers. However, its oncogenic functions have not been fully elucidated.