Angiotensin II (Ang II) is a pro-oxidant and fibrogenic cytokine. We investigated the role of NADPH oxidase in Ang II–induced effects hepatic stellate cells (HSCs), cell type. Human HSCs express mRNAs key components nonphagocytic oxidase. phosphorylated p47phox, regulatory subunit oxidase, induced reactive oxygen species formation via activity. AKT MAPKs increased AP-1 DNA binding redox-sensitive manner. stimulated synthesis, migration, procollagen α1(I) mRNA expression, secretion TGF-β1...

This study assesses the controversial role of mitochondrial permeability transition (MPT) in apoptosis. In primary rat hepatocytes expressing an IκB superrepressor, tumor necrosis factor alpha (TNFα) induced apoptosis as shown by nuclear morphology, DNA ladder formation, and caspase 3 activation. Confocal microscopy showed that TNFα onset MPT depolarization beginning 9 h after treatment. Initially, occurred only a subset mitochondria; however, 12 treatment, virtually all mitochondria were...

Cyclosporin A (CsA) shows cytoprotective properties in many cellular and vivo models that may depend on interference of the interaction cyclophilin with calcineurin or D mitochondrial permeability transition (PT) pore. The nonimmunosuppressive cyclosporin derivative<i>N</i>-methyl-4-valine-cyclosporin (PKF220-384) inhibits (MPT) like CsA but without inactivation. PKF220-384 has been used to discriminate between PT pore- mediated effects is no longer available. Here, we evaluated another...

To simulate ischemia and reperfusion, cultured rat hepatocytes were incubated in anoxic buffer at pH 6.2 for 4 h reoxygenated 7.4. During anoxia, intracellular (pH i ) decreased to 6.3, mitochondria depolarized, ATP &lt;1% of basal values, but the mitochondrial permeability transition (MPT) did not occur as assessed by confocal microscopy from redistribution cytosolic calcein into mitochondria. Moreover, cell viability remained &gt;90%. After reperfusion 7.4, returned 7.2, MPT occurred, most...

We have recently purified a rat brain membrane-bound nonlysosomal ceramidase (El Bawab, S., Bielawska, A., and Y. A. Hannun (1999) <i>J. Biol. Chem.</i> 274, 27948–27955). Using peptide sequences obtained from the enzyme, we report here cloning of human isoform. The deduced amino acid sequence protein did not show any similarity with proteins known function but was homologous to three putative <i>Arabidospis thaliana</i>, <i>Mycobacterium tuberculosi</i>s, <i>Dictyostelium discoideum</i>....

The c-Jun NH2-terminal kinase (JNK) is involved in the regulation of cell death, but its role tumor necrosis factor (TNF)-alpha- and Fas-mediated apoptosis primary cells not well defined. In rat hepatocytes expressing an IkappaB superrepressor, JNK inhibitor SP600125 strongly decreased TNF-alpha-induced caspase 3 activation, DNA laddering. contrast, did rescue mouse from Fas-induced apoptosis. Apoptosis hepatocytes, induced by human TNF-alpha, was blocked SP600125, indicating that...

The endocannabinoid system is an important regulator of hepatic fibrogenesis. In this study, we determined the effects 2-arachidonoyl glycerol (2-AG) on stellate cells (HSCs), main fibrogenic cell type in liver. Culture-activated HSCs were highly susceptible to 2-AG-induced death with >50% at 10 microM after 18 h treatment. HSC showed typical features apoptosis such as PARP- and caspase 3-cleavage depended reactive oxygen species (ROS) formation. Confocal microscopy revealed mitochondria...

In Brief Objective: To determine some of the mechanisms involved in insulin resistance immediately following burn trauma, and to efficacy PPAR-α agonism for alleviating this population. Summary Background Data: Hyperglycemia especially burns, is well documented. However, underlying not understood, there are limited treatment options. Methods: Twenty-one children 4 16 years age with >40% total body surface area burns were enrolled a double-blind, prospective, placebo-controlled randomized...

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a wide range of malignant cells. However, several cancers, including human hepatoma, are resistant to TRAIL. In this study, we analyzed TRAIL-induced pro- and antiapoptotic signaling pathways hepatoma Nuclear k B (NF- B) was found be critical the PLC/PRF/5, HepG2, Hep3B cell lines. NF- activation preceded by I Bα kinase (IKK) degradation depended on TRAF2, B-inducing (NIK), IKK1, IKK2. Accordingly,...

Carbon fiber reinforced plastics (CFRP) sandwich structure with the aluminum honeycomb core (CFRP-SS-AH) is a type of lightweight and energy absorption in mechanical engineering fields. Filling materials hexagon cavity expands characteristics CFRP-SS-AH. In this paper, experimental test numerical analysis are conducted to explore CFRP material-filled (CFRP-SS-RM-AH) under quasi-static transverse loading. The typical load-displacement curves evaluation indicators CFRP-SS-AH, CFRP-SS-RM (CFRP...

Neurofilaments in cerebrospinal fluid (CSF) and blood are considered promising biomarkers of amyotrophic lateral sclerosis (ALS) because their levels can be significantly increased patients with ALS. However, the roles neurofilaments, especially prognosis ALS inconsistent. We performed a meta-analysis to explore prognostic neurofilaments patients.

To institute intensive insulin therapy protocol in an acute pediatric burn unit and study the mechanisms underlying its benefits.Prospective, randomized study.An a tertiary teaching hospital.Children, 4-18 yrs old, with total body surface area burned > or =40% who arrived within 1 wk after injury were enrolled study.Patients to one of two groups. Intensive maintained blood glucose levels between 80 110 mg/dL. Conventional < =215 mg/dL.Twenty patients included data analysis consisting resting...

Metformin (Met) has antitumor effects on various cancers, but it is still unclear whether exerts a reversible effect endocrine resistance in breast cancer (BC) patients. In the present survey, metformin's tamoxifen-resistant MCF cells (The cell line was established at Michigan Cancer Foundation, hence name cell) were evaluated and molecular mechanism explored.We constructed BC MCF-7R, then applied Cell Counting Kit-8 (CCK-8), flow cytometry, EdU assessments to determine growth apoptosis of...

Insulin resistance is often associated with increased levels of intracellular triglycerides, diacylglycerol and decreased fat β-oxidation. It was unknown if this relationship present in patients acute insulin induced by trauma. A double blind placebo controlled trial conducted 18 children severe burn injury. Metabolic studies to assess whole body palmitate oxidation sensitivity, muscle biopsies for mitochondrial oxidation, diacylglycerol, fatty acyl Co-A carnitine concentrations, magnetic...

Lithium has been shown to delay the progression of Alzheimer’s disease reduce prevalence dementia. However, its narrow therapeutic index and numerous toxic effects at conventional dosage limited long-term use older subjects. Here, we tested effect low-dose lithium on cognitive impairment pathology alterations in a mouse model disease, amyloid precursor protein/presenilin-1 (APP/PS1) transgenic mouse. We found that both chronic acute administration dose-dependently increased blood brain...

Abstract Background The epigenetic abnormality of tumor-associated genes contributes to the pathogenesis colorectal carcinoma (CRC). However, methylation in cancer is still poorly characterized. Method By integration DNA data from GEO database and gene expression Cancer Genome Atlas database, aberrantly methylated involved CRC tumorigenesis were identified. Subsequent vitro experiments further validated their role CRC. Results We performed integrative genomic analysis identified HPSE2, a...

Thiamine deficiency is a well-known risk factor for the development of severe encephalopathy, such as Wernicke encephalopathy and Korsakoff syndrome, but underlying mechanism still mysterious. This study aims to investigate expression levels thiamine metabolism genes in different tissues their impact on brain susceptibility deficiency. The mRNA protein four known be associated with metabolism: pyrophosphokinase-1 ( Tpk ), Solute carrier family 19 member 2 Slc19a2 Slc19a3 , Slc25a19 brain,...

Angiotensin II (Ang II) is a pro-oxidant and fibrogenic cytokine. We investigated the role of NADPH oxidase in Ang II–induced effects hepatic stellate cells (HSCs), cell type. Human HSCs express mRNAs key components nonphagocytic oxidase. phosphorylated p47phox, regulatory subunit oxidase, induced reactive oxygen species formation via activity. AKT MAPKs increased AP-1 DNA binding redox-sensitive manner. stimulated synthesis, migration, procollagen α1(I) mRNA expression, secretion TGF-β1...

Inflammation plays an important role in the development and progression of non-alcoholic steatohepatitis (NASH), NASH is a powerful driving force for fibrosis. The neutrophil-to-lymphocyte ratio (NLR) simple emerging indicator inflammation. We aimed to assess potential association between NLR histological severity fatty liver disease (NAFLD).