High-performance dendritic contrast agents for X-ray computed tomography imaging using potent tetraiodobenzene derivatives.

The use of computed tomography (CT) for vascular imaging is critical in medical emergencies requiring urgent diagnostic decisions, such as cerebral ischemia and many cardiovascular diseases. Small-molecule iodinated contrast media are often injected intravenously as radiopaque agents during CT imaging to achieve high contrast enhancement of vascular systems. The rapid excretion rate of these agents is overcome by injecting a significantly high dose of iodine, which can have serious side effects.

The protective role of NAD(P)H:quinone oxidoreductase 1 on acetaminophen-induced liver injury is associated with prevention of adenosine triphosphate depletion and improvement of mitochondrial dysfunction.

Unlabelled: An overdose of acetaminophen (APAP) causes hepatotoxicity due to its metabolite, N-acetyl-p-benzoquinone imine.

Nad(p)h: quinone oxidoreductase 1 (NQO1) is an important enzyme for detoxification, because it catabolizes endogenous/exogenous quinone to hydroquinone. Although various studies have suggested the possible involvement of NQO1 in APAP-induced hepatotoxicity, its precise role in this remains unclear.

NAD(P)H:quinone oxidoreductase 1 activation reduces blood pressure through regulation of endothelial nitric oxide synthase acetylation in spontaneously hypertensive rats.

Background: Endothelial nitric oxide synthase (eNOS) is involved in blood pressure (BP) regulation through the production of nitric oxide. Sirtuin I (SIRT1), an NAD-dependent protein deacetylase, promotes vascular relaxation through deacetylation and activation of eNOS. β-Lapachone (βL) increases the cellular NAD(+)/NADH ratio by activating

Nad(p)h: quinone oxidoreductase 1 (NQO1).

Ursodeoxycholic acid inhibits liver X receptor α-mediated hepatic lipogenesis via induction of the nuclear corepressor SMILE.

Small heterodimer partner interacting leucine zipper protein (SMILE) has been identified as a nuclear corepressor of the nuclear receptor (NRs) family. Here, we examined the role of SMILE in the regulation of nuclear receptor liver X receptor (LXR)-mediated sterol regulatory element binding protein-1c (SREBP-1c) gene expression. We found that SMILE inhibited T0901317 (T7)-induced transcriptional activity of LXR, which functions as a major regulator of lipid metabolism by inducing SREBP-1c, fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) gene expression.

Enhanced activation of NAD(P)H: quinone oxidoreductase 1 attenuates spontaneous hypertension by improvement of endothelial nitric oxide synthase coupling via tumor suppressor kinase liver kinase B1/adenosine 5'-monophosphate-activated protein kinase-mediated guanosine 5'-triphosphate cyclohydrolase 1 preservation.

Aims: Guanosine 5'-triphosphate cyclohydrolase-1 (GTPCH-1) is a rate-limiting enzyme in de-novo synthesis of tetrahydrobiopterin (BH4), an essential cofactor for endothelial nitric oxide synthase (eNOS) coupling. Adenosine 5'-monophosphate-activated protein kinase (AMPK) is crucial for GTPCH-1 preservation, and tumor suppressor kinase liver kinase B1 (LKB1), an upstream kinase of AMPK, is activated by NAD-dependent class III histone deacetylase sirtuin 1 (SIRT1)-mediated deacetylation. β-Lapachone has been shown to increase cellular NAD/NADH ratio via

Nad(p)h: quinone oxidoreductase 1 (NQO1) activation.

Protection of NAD(P)H:quinone oxidoreductase 1 against renal ischemia/reperfusion injury in mice.

Unlabelled: Ischemia/reperfusion (I/R) is the most common cause of acute renal injury. I/R-induced reactive oxygen species (ROS) are thought to be a major factor in the development of acute renal injury by promoting the initial tubular damage.

Nad(p)h: quinone oxidoreductase 1 (NQO1) is a well-known antioxidant protein that regulates ROS generation.

Protective role of NAD(P)H:quinone oxidoreductase 1 (NQO1) in cisplatin-induced nephrotoxicity.

Although cisplatin is widely used as an anti-cancer agent, its use is significantly limited because of its tendency to induce nephrotoxicity through poorly understood mechanisms. NAD(P)H:quinone oxidoreductase 1 (NQO1) is well known to regulate ROS generation. The purpose of this study was to investigate whether NQO1 modulates cisplatin-induced renal failure associated with NADPH oxidase (NOX)-derived ROS production in an animal model.

Scoparone inhibits adipocyte differentiation through down-regulation of peroxisome proliferators-activated receptor γ in 3T3-L1 preadipocytes.

This study was performed to investigate the effect of scoparone on the differentiation of 3T3-L1 preadipocytes. Scoparone inhibited triglyceride (TG) accumulation in the mature adipocytes, evidenced by Oil-red O staining and intracellular quantification. Real time-PCR analysis showed that scoparone significantly down-regulated the mRNA expression of key adipogenic transcription factors, PPARγ, C/EBPα, compared with mature adipocytes.

Inverse agonist of nuclear receptor ERRγ mediates antidiabetic effect through inhibition of hepatic gluconeogenesis.

Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder with diverse pathological manifestations and is often associated with abnormal regulation of hepatic glucose production. Many nuclear receptors known to control the hepatic gluconeogenic program are potential targets for the treatment of T2DM and its complications. Nevertheless, the therapeutic potential of the estrogen-related receptor γ (ERRγ) in T2DM remains unknown.

NQO1 activation regulates angiotensin-converting enzyme shedding in spontaneously hypertensive rats.

Aims: Angiotensin-converting enzyme (ACE) plays a key role in blood pressure (BP) homeostasis via regulation of angiotensin II. Active ACE ectodomain is enzymatically cleaved and released into body fluids, including plasma, and elevated plasma ACE levels are associated with increased BP. β-lapachone (βL) has been shown to increase cellular NAD(+)/NADH ratio via activation of NAD(P)H:quinone oxidoreductase 1 (NQO1).

The orphan nuclear receptor small heterodimer partner negatively regulates pancreatic beta cell survival and hyperglycemia in multiple low-dose streptozotocin-induced type 1 diabetic mice.

The small heterodimer partner (SHP; NR0B2) regulates the transcription of a variety of target genes and controls a variety of physiological functions in various tissues. However, the role of SHP in beta cell has not been fully determined yet. We used SHP knockout (SHP KO) mice to investigate the role of SHP in multiple low-dose streptozotocin (MLDS)-induced diabetes.

In vivo imaging of islet transplantation using PLGA nanoparticles containing iron oxide and indocyanine green.

Purpose: We determined whether poly(lactic-co-glycolic acid) nanoparticles would be a useful reagent for the successful monitoring of isolated islets by magnetic resonance imaging and optical imaging systems, without clinically relevant toxicity in vitro or in vivo.

Methods: We used iron oxide for MR imaging and a cyanide dye approved by the Food and Drug Administration (indocyanine green) for optical imaging and estimated the in vivo detection of transplanted pancreatic islets.

Results: The poly(lactic-co-glycolic acid) nanoparticles were associated with the islets in vitro and were successfully detected by 4.

Insulin directly regulates steroidogenesis via induction of the orphan nuclear receptor DAX-1 in testicular Leydig cells.

Testosterone level is low in insulin-resistant type 2 diabetes. Whether this is due to negative effects of high level of insulin on the testes caused by insulin resistance has not been studied in detail. In this study, we found that insulin directly binds to insulin receptors in Leydig cell membranes and activates phospho-insulin receptor-β (phospho-IR-β), phospho-IRS1, and phospho-AKT, leading to up-regulation of DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) gene expression in the MA-10 mouse Leydig cell line.

Davallialactone protects against acetaminophen overdose-induced liver injuries in mice.

Oxidative stress is closely associated with acetaminophen (APAP)-induced toxicity. Davallialactone (DAVA), a hispidin analog derived from the mushroom Inonotus xeranticus, has antioxidant properties. This study evaluated whether DAVA plays protective roles against APAP hepatotoxicity in mice.

Increased vulnerability to β-cell destruction and diabetes in mice lacking NAD(P)H:quinone oxidoreductase 1.

NAD(P)H:quinone oxidoreductase 1 (NQO1) has been known to protect cells against stressors, including the diabetogenic reagent streptozotocin (STZ). The present study demonstrated that NQO1 deficiency resulted in increased pancreatic β-cell death induced by multiple low dose of STZ (MLDS) injections. NQO1 knockout (KO) mice showed hyperglycemia, body weight loss, impaired glucose clearance rate and a lower plasma insulin level after MLDS treatment.

Phosphoenolpyruvate carboxykinase and glucose-6-phosphatase are required for steroidogenesis in testicular Leydig cells.

Cyclic AMP (cAMP) induces steroidogenic enzyme gene expression and stimulates testosterone production in Leydig cells. Phosphoenolpyruvate carboxykinase (PEPCK) is expressed in Leydig cells, but its role has not been defined. In this study, we found that PEPCK and glucose-6-phosphatase (Glc-6-Pase) are increased significantly following cAMP treatment of mouse Leydig cells.

Susceptibility to gold nanoparticle-induced hepatotoxicity is enhanced in a mouse model of nonalcoholic steatohepatitis.

Although the safety of gold nanoparticle (AuNP) use is of growing concern, most toxicity studies of AuNPs had focused on their chemical characteristics, including their physical dimensions, surface chemistry, and shape. The present study examined the susceptibility of rodents with healthy or damaged livers to AuNP-induced hepatotoxicity. To induce a model of liver injury, mice were fed a methionine- and choline-deficient (MCD) diet for 4 weeks.

Prevention of salt-induced renal injury by activation of NAD(P)H:quinone oxidoreductase 1, associated with NADPH oxidase.

NADPH oxidase (NOX) is a predominant source of reactive oxygen species (ROS), and the activity of NOX, which uses NADPH as a common rate-limiting substrate, is upregulated by prolonged dietary salt intake. β-Lapachone (βL), a well-known substrate of NAD(P)H:quinone oxidoreductase 1 (NQO1), decreases the cellular NAD(P)H/NAD(P)(+) ratio via activation of NQO1. In this study, we evaluated whether NQO1 activation by βL modulates salt-induced renal injury associated with NOX-derived ROS regulation in an animal model.

Antiatherogenic effect of antioxidant polyphenols from Phellinus baumii in apolipoprotein E-deficient mice.

Aims: The present study was carried out to investigate the antiatherosclerotic effect of antioxidant polyphenols from Phellinus baumii (PBE) in apolipoprotein E-deficient (apoE-/-) mice.

Methods And Results: apoE-/- mice were randomly divided into three groups: mice on a normal chow diet comprised the normal group, mice on an atherogenic diet plus vehicle were the control group, and mice on an atherogenic diet plus PBE (500 mg/kg) comprised the PB500 group. After 8 weeks of treatment, the plasma lipids and cytokine levels were measured.

Hepatoprotective effect of Platycodon grandiflorum against chronic ethanol-induced oxidative stress in C57BL/6 mice.

Aims: This study was carried out to evaluate the hepatoprotective effect of Platycodon grandiflorum (PG) in ethanol (EtOH)-induced liver damage.

Methods And Results: PG treatment (both the total extract and saponin fraction) significantly blocked EtOH-induced oxidative stress through the preservation of activities of antioxidant enzymes in HepG2 cells. Furthermore, while the administration of EtOH to C57BL/6 mice for 6 weeks induced liver damage, along with a significant increase in plasma glutamic oxalacetic transaminase, glutamic pyruvic transaminase, hepatic triglyceride and thiobarbituric acid reactive substance levels, PG treatment significantly decreased glutamic oxalacetic transaminase, glutamic pyruvic transaminase, hepatic triglyceride and thiobarbituric acid reactive substance levels compared with the EtOH-treated control group (p < 0.

Activation of NAD(P)H:quinone oxidoreductase ameliorates spontaneous hypertension in an animal model via modulation of eNOS activity.

Aims: Hypertension is one of the most common human diseases worldwide, and extensive research efforts are focused upon the identification and utilizing of novel therapeutic drug targets. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is an important regulator of blood pressure (BP). β-Lapachone (βL), a well-known substrate of NAD(P)H:quinone oxidoreductase (NQO1), increases the cellular NAD(+)/NADH ratio via the activation of NQO1.

Hepatoprotective effects of chestnut (Castanea crenata) inner shell extract against chronic ethanol-induced oxidative stress in C57BL/6 mice.

This study was carried out to evaluate the protective effects of chestnut inner shell extract (CISE) on chronic ethanol-induced oxidative stress in liver. Mice were fed a control liquid diet (Normal-control), liquid diet containing ethanol alone (EtOH+Vehicle), or were administered CISE and ethanol (EtOH+CISE) for 6 weeks. Administration of ethanol induced liver damage with significant increase of plasma GOT, GPT, hepatic triglyceride (TG) and thiobarbituric acid reactive substance (TBARS) levels.

A Phellinus baumii extract reduces obesity in high-fat diet-fed mice and absorption of triglyceride in lipid-loaded mice.

This study evaluated the anti-obesity effects of Phellinus baumii extract (PBE) in high-fat diet (HFD)-fed mice. Male 8-week-old C57BL/6 mice were randomly divided into four groups: control, normal chow diet plus vehicle; HFD-control, high-fat plus vehicle; HFD plus orlistat (Xenical(®), Roche, Basel, Switzerland) (50 mg/kg); and HFD plus PBE (500 mg/kg). PBE was administered daily by oral gavage for 12 weeks.

Antioxidant effects of the chestnut (Castanea crenata) inner shell extract in t-BHP-treated HepG2 cells, and CCl4- and high-fat diet-treated mice.

The antioxidant effects of chestnut inner shell extract (CISE) were investigated in a tert-butylhydroperoxide (t-BHP)-treated HepG2 cells, and in mice that were administered carbon tetrachloride (CCl(4)) and fed a high-fat diet (HFD). Pre-incubation with CISE significantly blocked the oxidative stress induced by t-BHP treatment in HepG2 cells (P<0.05) and preserved the activities of catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase compared to group treated with t-BHP only.

Differential modulatory effects of rosiglitazone and pioglitazone on white adipose tissue in db/db mice.

Aims: this study was performed to clarify the different action mechanisms through which rosiglitazone and pioglitazone regulate lipogenesis in white adipose tissues of db/db mice, an animal model of diabetes.

Main Methods: male C57BLKS/J-Lepr(db/db) (db/db) mice were used for all experiments. Rosiglitazone or pioglitazone were administered once daily by oral gavage for 4 weeks at concentrations of 20mg/kg and 75 mg/kg, respectively.