Developmental programming of thermonastic leaf movement

Plants exhibit diverse polar behaviors in response to directional and non-directional environmental signals, termed tropic and nastic movements, respectively. The ways in which plants incorporate directional information into tropic behaviors is well understood, but it is less well understood how non-directional stimuli, such as ambient temperatures, specify the polarity of nastic behaviors. Here, we demonstrate that a developmentally programmed polarity of auxin flow underlies thermo-induced leaf hyponasty in Arabidopsis (Arabidopsis thaliana). In warm environments, PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) stimulates auxin production in the leaf. This results in the accumulation of auxin in leaf petioles, where PIF4 directly activates a gene encoding the PINOID (PID) protein kinase. PID is involved in polarization of the auxin transporter PIN-FORMED 3 to the outer membranes of petiole cells. Notably, the leaf polarity-determining ASYMMETRIC LEAVES 1 (AS1) directs the induction of PID to occur predominantly in the abaxial petiole region. These observations indicate that the integration of PIF4-mediated auxin biosynthesis and polar transport, and the AS1-mediated developmental shaping of polar auxin flow, coordinate leaf thermonasty, which facilitates leaf cooling in warm environments. We believe that leaf thermonasty is a suitable model system for studying the developmental programming of environmental adaptation in plants

Hepatocyte growth factor suppresses vascular endothelial growth factor-induced expression of endothelial ICAM-1 and VCAM-1 by inhibiting the nuclear factor-kappaB pathway

Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are potent angiogenic factors that have been used clinically to induce angiogenesis. However, concerns have been raised about VEGF because of its proinflammatory actions, which include enhancing the adhesion of leukocytes to endothelial cells. We have examined the possible antiinflammatory effects of HGF on the vasculature. HGF, unlike VEGF, did not alter leukocyte adhesion to endothelial cells. Instead it inhibited VEGF-induced leukocyte-endothelial cell interactions and the endothelial expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). In a skin inflammation model, VEGF-treated mice showed a significant increase of leukocytes infiltrated or adherent to the luminal surface of blood vessels, as compared with vehicle- or HGF-treated mice. The VEGF effect was markedly suppressed by coadministration of HGF. RT-PCR and promoter analysis revealed that HGF downregulated VEGF-mediated expression of ICAM-1 and VCAM-1 at the transcriptional level. Furthermore, these inhibitory effects coincided with suppression of IkappaB kinase activity, and this in turn prevented the activation of the inflammatory transcription factor NF-kappaB. Taken together, our results demonstrate that HGF suppresses VEGF-induced inflammation presumably by inhibiting the endothelial NF-kappaB pathway. This suggests that combined treatment with HGF and VEGF could be superior to treatment with either factor alone for enhancing therapeutic angiogenesis while avoiding inflammation

Dose-Dependent Neuroprotective Effect of Standardized Bee Venom Phospholipase A2 Against MPTP-Induced Parkinson’s Disease in Mice

Parkinson’s disease (PD) is a chronic progressive neurodegenerative movement disorder characterized by the selective loss of dopaminergic neurons within the substantia nigra (SN). While the precise etiology of dopaminergic neuronal demise is elusive, multiple lines of evidence indicate that neuroinflammation is involved in the pathogenesis of PD. We have previously demonstrated that subcutaneous administration of bee venom (BV) phospholipase A2 (bvPLA2) suppresses dopaminergic neuronal cell death in a PD mouse model. In the present study, we established standardized methods for producing bvPLA2 agent isolated from crude BV at good manufacturing practice (GMP) facility. The therapeutic efficacy of purified bvPLA2 agent was examined in MPTP-induced PD mice. Importantly, administration of purified bvPLA2 in a dose-dependent manner reversed motor deficits in PD mice as well as inhibited loss of dopaminergic neurons within the SN of PD mice. The concentration-dependent action of standardized bvPLA2 appeared to be related to the induction of CD4+CD25+Foxp3+ regulatory T cells (Tregs), which, in part, inhibits T helper 1 (Th1) and Th17 polarization and suppresses microglial activation in PD mice. Taken together, these results suggest that standardized bvPLA2 purified from BV shows a neuroprotective effect against PD and thus has a potential target for treatment of PD

Deficiency of peroxiredoxin 2 exacerbates angiotensin II-induced abdominal aortic aneurysm

Abdominal aortic aneurysm: Potential enzyme biomarker identified An enzyme with antioxidant properties may provide a biomarker and therapeutic agent to help treat abdominal aortic aneurysm (AAA). AAA involves the structural deterioration of the aorta through chronic inflammation and oxidative stress, and can trigger life-threatening artery rupture. An antioxidant enzyme called peroxiredoxin 2 (PRDX2) is increased in patients with ruptures, but whether its role in AAA is beneficial or detrimental is unclear. Goo Taeg Oh at the Ewha Womans University in Seoul, Jong-Gil Park at the Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea, and co-workers examined the effect of PRDX2 on AAA progression. PRDX2 suppressed structural damage in mice, limiting artery dilation and protein degradation. Loss of PRDX2 accelerated AAA development. Measuring levels of PRDX2 may indicate AAA severity in patients, while boosting the enzyme could repair aortic damage

Okanin, a chalcone found in the genus Bidens, and 3-penten-2-one inhibit inducible nitric oxide synthase expression via heme oxygenase-1 induction in RAW264.7 macrophages activated with lipopolysaccharide

Excess production of nitric oxide by activated macrophages via inducible nitric oxide synthase leads to the development of various inflammatory diseases. Heme oxygenase-1 expression via activation of nuclear factor-erythroid 2-related factor 2 inhibits nitric oxide production and inducible nitric oxide synthase expression in activated macrophages. Okanin is one of the most abundant chalcones found in the genus Bidens (Asteraceae) that is used as various folk medications in Korea and China for treating inflammation. Here, we found that okanin (possessing the α-β unsaturated carbonyl group) induced heme oxygenase-1 expression via nuclear factor-erythroid 2-related factor 2 activation in RAW264.7 macrophages. 3-Penten-2-one, of which structure, as in okanin, possesses the α-β unsaturated carbonyl group, also induced nuclear factor-erythroid 2-related factor 2-dependent heme oxygenase-1 expression, while both 2-pentanone (lacking a double bond) and 2-pentene (lacking a carbonyl group) were virtually inactive. In lipopolysaccharide-activated RAW264.7 macrophages, both okanin and 3-penten-2-one inhibited nitric oxide production and inducible nitric oxide synthase expression via heme oxygenase-1 expression. Collectively, our findings suggest that by virtue of its α-β unsaturated carbonyl functional group, okanin can inhibit nitric oxide production and inducible nitric oxide synthase expression via nuclear factor-erythroid 2-related factor 2-dependent heme oxygenase-1 expression in lipopolysaccharide-activated macrophages

Solitary Extramedullary Plasmacytoma of the Liver without Systemic Monoclonal Gammopathy

Extramedullary plasmacytoma of the liver is a very rare tumor. Although a few cases of extramedullary plasmacytoma of the liver have been reported, we could not find any report on truly localized extramedullary plasmacytoma of the liver in the literature. The patient was a 63-yr-old man who exhibited a solitary liver mass on dynamic computed tomography and magnetic resonance imaging. Histologically, the tumor was composed of mature plasma cells with mild atypia. Immunohistochemistry demonstrated monoclonal IgG and Kappa light chain expression. Bone marrow examination revealed no abnormalities. There was no evidence of a monoclonal protein in the serum and urine, lytic bone lesions, anemia, renal insufficiency, and hypercalcemia. The patient was treated with 5,000 cGy of radiotherapy, and the tumor disappeared 6 months after treatment

Ginseng Berry Extract Prevents Atherogenesis via Anti-Inflammatory Action by Upregulating Phase II Gene Expression

Ginseng berry possesses higher ginsenoside content than its root, which has been traditionally used in herbal medicine for many human diseases, including atherosclerosis. We here examined the antiatherogenic effects of the Korean ginseng berry extract (KGBE) and investigated its underlying mechanism of action in vitro and in vivo. Administration of KGBE decreased atherosclerotic lesions, which was inversely correlated with the expression levels of phase II genes to include heme oxygenase-1 (HO-1) and glutamine-cysteine ligase (GCL). Furthermore, KGBE administration suppressed NF-κB-mediated expression of atherogenic inflammatory genes (TNF-α, IL-1β, iNOS, COX-2, ICAM-1, and VCAM-1), without altering serum cholesterol levels, in ApoE-/- mice fed a high fat-diet. Treatment with KGBE increased phase II gene expression and suppressed lipopolysaccharide-induced reactive oxygen species production, NF-κB activation, and inflammatory gene expression in primary macrophages. Importantly, these cellular events were blocked by selective inhibitors of HO-1 and GCL. In addition, these inhibitors reversed the suppressive effect of KGBE on TNF-α-mediated induction of ICAM-1 and VCAM-1, resulting in decreased interaction between endothelial cells and monocytes. These results suggest that KGBE ameliorates atherosclerosis by inhibiting NF-κB-mediated expression of atherogenic genes via upregulation of phase II enzymes and thus has therapeutic or preventive potential for atherosclerosis

Ginkgo biloba extract (GbE) enhances the anti-atherogenic effect of cilostazol by inhibiting ROS generation

In this study, the synergistic effect of 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) and Ginkgo biloba extract (GbE) was examined in apolipoprotein E (ApoE) null mice. Co-treatment with GbE and cilostazol synergistically decreased reactive oxygen species (ROS) production in ApoE null mice fed a high-fat diet. Co-treatment resulted in a significantly decreased atherosclerotic lesion area compared to untreated ApoE mice. The inflammatory cytokines and adhesion molecules such as monocyte chemoattractant-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and VCAM-1 which can initiate atherosclerosis were significantly reduced by the co-treatment of cilostazol with GbE. Further, the infiltration of macrophages into the intima was decreased by co-treatment. These results suggest that co-treatment of GbE with cilostazol has a more potent anti-atherosclerotic effect than treatment with cilostazol alone in hyperlipidemic ApoE null mice and could be a valuable therapeutic strategy for the treatment of atherosclerosis

Physiological Functions of Thiol Peroxidases (Gpx1 and Prdx2) during Xenopus laevis Embryonic Development

Glutathione peroxidase 1 (Gpx1) and peroxiredoxin 2 (Prdx2) belong to the thiol peroxidase family of antioxidants, and have been studied for their antioxidant functions and roles in cancers. However, the physiological significance of Gpx1 and Prdx2 during vertebrate embryogenesis are lacking. Currently, we investigated the functional roles of Gpx1 and Prdx2 during vertebrate embryogenesis using Xenopus laevis as a vertebrate model. Our investigations revealed the zygotic nature of gpx1 having its localization in the eye region of developing embryos, whereas prdx2 exhibited a maternal nature and were localized in embryonic ventral blood islands. Furthermore, the gpx1-morphants exhibited malformed eyes with incompletely detached lenses. However, the depletion of prdx2 has not established its involvement with embryogenesis. A molecular analysis of gpx1-depleted embryos revealed the perturbed expression of a cryba1-lens-specific marker and also exhibited reactive oxygen species (ROS) accumulation in the eye regions of gpx1-morphants. Additionally, transcriptomics analysis of gpx1-knockout embryos demonstrated the involvement of Wnt, cadherin, and integrin signaling pathways in the development of malformed eyes. Conclusively, our findings indicate the association of gpx1 with a complex network of embryonic developmental pathways and ROS responses, but detailed investigation is a prerequisite in order to pinpoint the mechanistic details of these interactions.</p&gt

Hepatoprotective Activity of Licorice Water Extract against Cadmium-induced Toxicity in Rats

Licorice is commonly used as a cure for digestive disorders and as a detoxification agent in East Asia. This study investigated the protective effect of licorice water extract against cadmium (CdCl2, Cd)-induced liver toxicity in rats. To induce acute toxicity, Cd (4 mg/kg body weight) was dissolved in normal saline and intravenously (i.v.) injected into rats. The rats then received either a vehicle or licorice water extract (50, 100 mg/kg/day) for 3 days, and were subsequently exposed to a single injection of Cd 24 h after the last licorice/vehicle treatment. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were significantly increased by Cd treatment. In contrast, pretreatment with licorice reduced ALT, AST and LDH. In histopathological analysis, licorice decreased the central necrosis around central veins, the peripheral hemorrhage around portal triads, the percentage of degenerative hepatic regions (%/mm2 hepatic parenchyma) and the number of degenerative hepatic cells (N/100 hepatic cells). Licorice also inhibited the increment of Bad (a BH3 domain-containing protein) translocation by Cd in liver cells. These results demonstrate that licorice could have a hepatoprotective effect by inhibiting the translocation of Bad to the mitochondria in Cd-intoxificated rats