Efficiency comparison of PGBR extract and γ-oryzanol in antioxidative stress and anti-inflammatory properties against metabolic syndrome.

This research aims to delineate the anti-inflammatory effect of pregerminated brown rice extract (PE) and γ-oryzanol on improving metabolic features of high-fat diet (HFD)-induced metabolic syndrome (MetS) mouse model. C57BL/6 mice were randomly divided into eight groups: regular diet (RD), HFD, HFD-combined treatment of 0.5, 5, or 10 mg kg-1  day-1 oral gavage γ-oryzanol, and 30, 300, or 600 mg kg-1  day-1 PE for 18 weeks. HFD-fed mice showed overweight, hyperglycemia, hyperlipidemia signs of metabolic disorder, and elevation of inflammatory cytokines such as IL-6, TNF-α, IFN-γ, NO, PGE2 in serum and MAPKs, transcription factor p65, iNOS, and MDA in the liver. In contrast, HFD-fed mice showed lower levels of adiponectin in serum and antiperoxidation enzymes GPx, SOD, and catalase in the liver. While HFD-fed mice cotreated with PE or γ-oryzanol, HFD-induced metabolic disorders, ROS, and inflammation were improved. The anti-MetS, antioxidative stress and anti-inflammation properties of PE were more potent than γ-oryzanol. PRACTICAL APPLICATIONS: Our study showed that PE or γ-oryzanol supplement could help control metabolic disorders, oxidative stress, chronic inflammation, and related complications.

Sinulariolide Inhibits Gastric Cancer Cell Migration and Invasion through Downregulation of the EMT Process and Suppression of FAK/PI3K/AKT/mTOR and MAPKs Signaling Pathways.

Cancer metastasis is the main cause of death in cancer patients; however, there is currently no effective method to predict and prevent metastasis of gastric cancer. Therefore, gaining an understanding of the molecular mechanism of tumor metastasis is important for the development of new drugs and improving the survival rate of patients who suffer from gastric cancer. Sinulariolide is an active compound isolated from the cultured soft coral Sinularia flexibilis. We employed sinulariolide and gastric cancer cells in experiments such as MTT, cell migration assays, cell invasion assays, and Western blotting analysis. Analysis of cell migration and invasion capabilities showed that the inhibition effects on cell metastasis and invasion increased with sinulariolide concentration in AGS and NCI-N87 cells. Immunostaining analysis showed that sinulariolide significantly reduced the protein expressions of MMP-2, MMP-9, and uPA, but the expressions of TIMP-1 and TIMP-2 were increased, while FAK, phosphorylated PI3K, phosphorylated AKT, phosphorylated mTOR, phosphorylated JNK, phosphorylated p38MAPK, and phosphorylated ERK decreased in expression with increasing sinulariolide concentration. From the results, we inferred that sinulariolide treatment in AGS and NCI-N87 cells reduced the activities of MMP-2 and MMP-9 via the FAK/PI3K/AKT/mTOR and MAPKs signaling pathways, further inhibiting the invasion and migration of these cells. Moreover, sinulariolide altered the protein expressions of E-cadherin and N-cadherin in the cytosol and Snail in the nuclei of AGS and NCI-N87 cells, which indicated that sinulariolide can avert the EMT process. These findings suggested that sinulariolide is a potential chemotherapeutic agent for development as a new drug for the treatment of gastric cancer.

Heme oxygenase-1 modulates microRNA expression in cultured astroglia: implications for chronic brain disorders.

BACKGROUND: Over-expression of the heme-degrading enzyme, heme oxygenase-1 (HO-1) promotes iron deposition, mitochondrial damage, and autophagy in astrocytes and enhances the vulnerability of nearby neuronal constituents to oxidative injury. These neuropathological features and aberrant brain microRNA (miRNA) expression patterns have been implicated in the etiopathogeneses of various neurodevelopmental and aging-related neurodegenerative disorders. OBJECTIVE: To correlate glial HO-1 overexpression with altered miRNA patterns, which have been linked to the aforementioned "core" neuropathological features. METHODS: miRNA microchip assays were performed on HMOX1- and sham-transfected primary rat astroglia and affected miRNAs were further validated by qPCR. The roles of the heme degradation products, carbon monoxide (CO), iron (Fe) and bilirubin on miRNA expression were assessed and salient mRNA targets of the impacted miRNAs were ascertained. RESULTS: In HMOX1-transfected astrocytes, rno-miR-140*, rno-miR-17, and rno-miR-16 were significantly up-regulated, and rno-miR-297, rno-miR-206, rno-miR-187, rno-miR-181a, rno-miR-138 and rno-miR-29c were down-regulated, compared to sham-transfected controls. CO and Fe were implicated in the HMOX1 effects, whereas bilirubin was inert or counteracted the HMOX1-related changes. mRNA levels of Ngfr, Vglut1, Mapk3, Tnf-α, and Sirt1, known targets of the down-regulated miRNAs and abnormal in various human brain disorders, were significantly increased in the HMOX-1-transfected astrocytes. CONCLUSIONS: In chronic CNS disorders, altered expression of salient miRNAs and their mRNA targets may contribute to the neural damage accruing from the over-expression of glial HO-1.

Schizophrenia-like features in transgenic mice overexpressing human HO-1 in the astrocytic compartment.

Delineation of key molecules that act epigenetically to transduce diverse stressors into established patterns of disease would facilitate the advent of preventive and disease-modifying therapeutics for a host of neurological disorders. Herein, we demonstrate that selective overexpression of the stress protein heme oxygenase-1 (HO-1) in astrocytes of novel GFAP.HMOX1 transgenic mice results in subcortical oxidative stress and mitochondrial damage/autophagy; diminished neuronal reelin content (males); induction of Nurr1 and Pitx3 with attendant suppression of their targeting miRNAs, 145 and 133b; increased tyrosine hydroxylase and α-synuclein expression with downregulation of the targeting miR-7b of the latter; augmented dopamine and serotonin levels in basal ganglia; reduced D1 receptor binding in nucleus accumbens; axodendritic pathology and altered hippocampal cytoarchitectonics; impaired neurovascular coupling; attenuated prepulse inhibition (males); and hyperkinetic behavior. The GFAP.HMOX1 neurophenotype bears resemblances to human schizophrenia and other neurodevelopmental conditions and implicates glial HO-1 as a prime transducer of inimical (endogenous and environmental) influences on the development of monoaminergic circuitry. Containment of the glial HO-1 response to noxious stimuli at strategic points of the life cycle may afford novel opportunities for the effective management of human neurodevelopmental and neurodegenerative conditions.

Unregulated brain iron deposition in transgenic mice over-expressing HMOX1 in the astrocytic compartment.

The mechanisms responsible for pathological iron deposition in the aging and degenerating mammalian CNS remain poorly understood. The stress protein, HO-1 mediates the degradation of cellular heme to biliverdin/bilirubin, free iron, and CO and is up-regulated in the brains of persons with Alzheimer's disease and Parkinson's disease. HO-1 induction in primary astroglial cultures promotes deposition of non-transferrin iron, mitochondrial damage and macroautophagy, and predisposes cocultured neuronal elements to oxidative injury. To gain a better appreciation of the role of glial HO-1 in vivo, we probed for aberrant brain iron deposition using Perls' method and dynamic secondary ion mass spectrometry in novel, conditional GFAP.HMOX1 transgenic mice that selectively over-express human HO-1 in the astrocytic compartment. At 48 weeks, the GFAP.HMOX1 mice exhibited increased deposits of glial iron in hippocampus and other subcortical regions without overt changes in iron-regulatory and iron-binding proteins relative to age-matched wild-type animals. Dynamic secondary ion mass spectrometry revealed abundant FeO⁻ signals in the transgenic, but not wild-type, mouse brain that colocalized to degenerate mitochondria and osmiophilic cytoplasmic inclusions (macroautophagy) documented by TEM. Sustained up-regulation of HO-1 in astrocytes promotes pathological brain iron deposition and oxidative mitochondrial damage characteristic of Alzheimer's disease-affected neural tissues. Curtailment of glial HO-1 hyperactivity may limit iron-mediated cytotoxicity in aging and degenerating neural tissues.

Usefulness of combination of pulmonary ventilation and perfusion scintigraphy on the diagnosis of children with unilateral hyperlucent lung.

OBJECTIVES: Unilateral hyperlucent lung on chest radiograph is uncommon in children. It is often found incidentally and always refers to Swyer-James syndrome, with decrease in pulmonary vascularity and air trapping during expiration. However, it may occasionally mimic other serious lung diseases such as pulmonary hypoplasia/aplasia, defect of pulmonary artery, and other primary pulmonary disorders. In this study, we hypothesized that there would be characteristic patterns in pulmonary ventilation and perfusion scintigraphy (V/Q scan) in children with unilateral hyperlucency on chest film, which could play an important role in differential diagnosis of this disease group explicitly. METHODS: Children with unilateral hyperlucency on chest radiograph had a detailed clinical examination and underwent echocardiography, chest computed tomography, selective pulmonary angiogram, flexible bronchoscopy, and pulmonary V/Q scan. RESULTS: A total of 10 cases were enrolled, including two cases of unilateral pulmonary artery agenesis, three cases of Swyer-James syndrome, two cases of agenesis of the right lung, one case of lobar emphysema, and two cases of tetralogy of fallot with left pulmonary artery stenosis. Besides, an overview of children with unilateral hyperlucent lung is provided, reviewing nine studies (171 patients), including our clinical experience, and finally an algorithm for diagnosis unilateral hyperlucent lung is proposed, based on the characteristics of V/Q scan. CONCLUSION: We chose a descriptive approach to the V/Q scan in children with unilateral hyperlucent lung on chest radiograph. This result enables us to promote the V/Q scan as a first-line tool in evaluating these patients and to avoid further unnecessary procedures.

Ganglioneuroma of posterior mediastinum in a 6-year-old girl: imaging for pediatric intrathoracic incidentaloma.

Intrathoracic tumor is a rare entity in the pediatric population and neurogenic tumors account for 40-50% of childhood intrathoracic tumors. They can cause severe symptoms, such as respiratory distress, neurological dysfunction and metabolic disturbances. Posterior mediastinal ganglioneuroma (GN) usually occurs in children and can be found accidentally. Precise preoperative diagnosis is very difficult and has a great influence on surgical intervention. Here, we report a 6-year-old girl with a posterior mediastinal GN that was found incidentally on chest radiography. Computed tomography and magnetic resonance imaging demonstrated a right paraspinal tumor with punctuate calcification and intraspinal extension. (18)F-fluorodeoxyglucose positron emission tomography revealed low-grade fluorodeoxyglucose avidity of this tumor. Computed tomography and magnetic resonance imaging can characterize GN and positron emission tomography is helpful for differentiating benign or malignant lesions.