HO-1 induction ameliorates experimental murine membranous nephropathy: anti-oxidative, anti-apoptotic and immunomodulatory effects.

Background: Therapeutic agents for membranous nephropathy (MN) remain ill-defined. Haeme oxygenase (HO)-1 is considered to play a protective role in various disorders. Here, we assessed the efficacy of HO-1 induction therapy for MN.

Identification and characterization of mouse Gas6 promoter.

In this study, we identify and characterize the promoter of the mouse Gas6 gene, a negative regulator of chondrogenic differentiation. We identified two highly conserved regions within the core Gas6 promoter, which are conserved among mouse, human, and rat Gas6 genes, named A-BOX and B-BOX. Basal transcriptional activity was significantly reduced after deletion of either the A-BOX or the latter half of the B-BOX.

Formic acid induces Yca1p-independent apoptosis-like cell death in the yeast Saccharomyces cerevisiae.

Formic acid disrupts mitochondrial electron transport and sequentially causes cell death in mammalian ocular cells by an unidentified molecular mechanism. Here, we show that a low concentration of formic acid induces apoptosis-like cell death in the budding yeast Saccharomyces cerevisiae, with several morphological and biochemical changes that are typical of apoptosis, including chromatin condensation, DNA fragmentation, externalization of phosphatidylserine, reactive oxygen species (ROS) production, loss of mitochondrial membrane potential and mitochondrion destruction. This process may not be dependent on the activation of Yca1p, the yeast caspase counterpart.

Tetramethylpyrazine inhibits activities of glioma cells and glutamate neuro-excitotoxicity: potential therapeutic application for treatment of gliomas.

We tested the herbal extract 2,3,5,6-tetramethylpyrazine (TMP) for possible therapeutic efficacy against a glioma cell line and against gliomas transplanted into rat brains. In the cultured glioma cells, 50 muM TMP significantly inhibited glutamate-induced increase in intracellular calcium. Significant cell damage (30%) and proliferation suppression (10%), however, occurred only at higher concentrations (200-400 microM).

Hypoxia/Reoxygenation induces nitric oxide and TNF-alpha release from cultured microglia but not astrocytes of the rat.

Hypoxia/reoxygenation (H/R) elicits neuronal cell injury and glial cell activation within the central nervous system (CNS). Neuroinflammation is a process that primarily results from the acute or chronic activation of glial cells. This overactive state of glial cells results in the increased release of nitric oxide (NO) and/or tumor necrosis factor alpha (TNF-alpha), a process which can lead to neuronal damage or death.

Lovastatin improves histological and functional outcomes and reduces inflammation after experimental traumatic brain injury.

Traumatic brain injury (TBI) triggers a complex sequence of inflammatory responses that contribute to secondary injury. Statins have demonstrated neuroprotective effects against brain injury, but the underlying mechanisms remain unclear. This study evaluated the effects of lovastatin on a rat model of controlled cortical impact (CCI) injury.

Rapid glia expression and release of proinflammatory cytokines in experimental Klebsiella pneumoniae meningoencephalitis.

The host immune/inflammatory response following CNS infection by Klebsiella pneumoniae remains poorly understood. Using a rat model of K. pneumoniae meningoencephalitis, we investigated the temporal profiles of brain proinflammatory cytokines and their cellular sources.

Tissue microarray-determined expression profiles of cyclooxygenase-2 in colorectal adenocarcinoma: association with clinicopathological parameters.

Accumulated evidence reveals that increased cyclooxygenase-2 (COX-2) is involved in the development of colorectal cancer. Our purpose was to quantitate COX-2 expression in colorectal cancers using tissue microarray analysis and look for an association with clinicopathological stage. Immunohistochemical analysis of COX-2 was performed in tissue microarray slides containing 90 specimens including 32 well-differentiated, 35 moderately differentiated, and 23 poorly differentiated colorectal adenocarcinomas.

Higher expression of epidermal growth factor receptor is associated with extracellular matrix metalloprotease inducer in colorectal adenocarcinoma: tissue microarray analysis of immunostaining score with clinicopathological parameters.

Aim: Extracellular matrix metalloprotease inducer (EMMPRIN) expression was demonstrated in several cancers, but its expression profile in colorectal cancers remains unclear. Epidermal growth factor receptor (EGFR) was reported to regulate EMMPRIN expression in human epithelial cancers. Our purpose was to determine EMMPRIN expression and its relationship with EGFR in colorectal cancers.

Dual effects of antioxidants in neurodegeneration: direct neuroprotection against oxidative stress and indirect protection via suppression of glia-mediated inflammation.

Oxidative stress, in which production of highly reactive oxygen species (ROS) and reactive nitrogen species (RNS) overwhelms antioxidant defenses, is a feature of many neurological diseases and neurodegeneration. ROS and RNS generated extracellularly and intracellularly by various processes initiate and promote neurodegeneration in CNS. ROS and RNS can directly oxidize and damage macromolecules such as DNA, proteins, and lipids, culminating in neurodegeneration in the CNS.

Increasing expression of extracellular matrix metalloprotease inducer in renal cell carcinoma: tissue microarray analysis of immunostaining score with clinicopathological parameters.

Aim: Renal tumor cell invasion is responsible for both local tissue destruction and distant metastasis. Invasion is largely mediated by matrix metalloproteases that are thought to be induced by tumor cell-derived extracellular matrix metalloprotease inducer (EMMPRIN) in surrounding fibroblasts. We hypothesized that EMMPRIN and matrix metalloproteinase-9 (MMP-9) are over-expressed in renal cell carcinoma.

Ursolic acid protects hippocampal neurons against kainate-induced excitotoxicity in rats.

Ursolic acid is the major component of extracts of the Chinese herb, Souyang. This study determines whether and how ursolic acid protects against kainate-induced excitotoxicity in rat hippocampus. Primary neuronal cultures of cells isolated from the hippocampi of 7-day-old rats were treated with 150 microM kainate.

Mediation of BMP7 neuroprotection by MAPK and PKC IN rat primary cortical cultures.

We have previously demonstrated that pretreatment with bone morphogenetic protein 7 (BMP7), a trophic factor in the TGFbeta superfamily, reduces ischemia-induced brain infarction induced by middle cerebral artery ligation in rats. Since the mitogen-activated protein kinase (MAPK) pathway is involved in many TGFbeta-mediated responses, we examined the interaction of BMP7 and MAPK in primary cultures obtained from the cerebral cortex of E16-17 rat embryos. Lactate dehydrogenase (LDH) in the media was used as an index of cell death.

Nitric oxide inhibition accelerates hypertension and induces perivascular inflammation in rats.

1. Inflammatory changes in peripheral arteries have been reported in animal models of hypertension. Whether they occur in cerebral arteries (CA) with hypertension induced by deprivation of endogenous nitric oxide (NO) remains unknown.

Role of circulating cytokines and chemokines in exertional heatstroke.

Objective: The interplay between inflammatory and anti-inflammatory cytokines, as well as chemokines, has not been well explored in exertional heatstroke.

Design: Prospective, observational study.

Patients: Seventeen military recruits who developed exertional heatstroke and 17 exertional controls who did not develop exertional heatstroke during the same training exercises.

Expression of bone morphogenetic proteins in the brain during normal aging and in 6-hydroxydopamine-lesioned animals.

Bone morphogenetic proteins (BMPs), BMP receptors (BMPRs), and endogenous BMP antagonists have been found to be critically important for the development of the central nervous system (CNS) and peripheral organs in mammals. There is also increasing evidence that this system has significant activity in the adult CNS. Accordingly, we studied the regional distribution of endogenous BMP ligand proteins, receptors, and antagonists during aging and after lesion of the midbrain dopamine pathways produced by 6-hydroxydopamine (6-OHDA).

Dobutamine inhibits monocyte chemoattractant protein-1 production and chemotaxis in human monocytes.

Unlabelled: It has been reported that, in patients with acute myocardial infarction or congestive heart failure, monocyte chemoattractant protein-1 (MCP-1) plays an important role in the development of inflammatory responses and that the level of MCP-1 is correlated with the severity of the disease. We conducted this study to investigate the effects of dobutamine and dopamine on lipopolysaccharide (LPS)-induced MCP-1 production in human monocytic THP-1 cells. Monocytes were incubated in vitro with LPS for 16 h at 37 degrees C in the presence or absence of dobutamine or dopamine.

Midodrine improves chronic hypotension in hemodialysis patients.

Background: The effects of midodrine on chronic hypotension in hemodialysis (HD) patients have not been well investigated.

Methods: We evaluated midodrine's effect on autonomic function and hemodynamics in 12 HD patients who had chronic systolic blood pressure less than 100 mm Hg. Midodrine (5.

Oxidative neurotoxicity in rat cerebral cortex neurons: synergistic effects of H2O2 and NO on apoptosis involving activation of p38 mitogen-activated protein kinase and caspase-3.

Oxidative stress in the brain has been increasingly associated with the development of numerous human neurological diseases. Microglia, activated upon neuronal injury or inflammatory stimulation, are known to release superoxide anion (*O(2) (-)), hydrogen peroxide (H(2)O(2)), and nitric oxide (NO), thereby further contributing to oxidative neurotoxicity. The reaction of NO and *O(2) (-), forming the toxic peroxynitrite (ONOO(-)), has been proposed to play a pathogenic role in neuronal injury.

Hypoxia/reoxygenation induces cell injury via different mechanisms in cultured rat cortical neurons and glial cells.

Hypoxia/reoxygenation (H/R) causes cell injury/death. We examined the protection by drugs intervening at various stages of the injury cascade in cultured neurons and glia. Primary cultures of rat cortical neurons and mixed glia were subjected to H/R.