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3,5-Dimethoxy-4-(3-(2-carbonyl-ethyldisulfanyl)-propionyl)-benzoic acid 4-guanidino-butyl ester: a novel twin drug that prevents primary cardiac myocytes from hypoxia-induced apoptosis.

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Leonurine possesses cardioprotective effects in myocardial ischemia due to its anti-apoptotic properties. However, the process to isolate and purify leonurine is difficult, because of its low content in the Herb Leonuri and its impurity. Moreover, the high dosage used indicates low potency of

(Aryloxyacetylamino)benzoic acid analogues: A new class of hypoxia-inducible factor-1 inhibitors.

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Structural modification of a compound discovered during screening using an HRE-dependent reporter assay has revealed a novel class of HIF-1 inhibitors, which potently inhibit the HIF-1alpha protein accumulation and its target gene expression under hypoxic conditions in human hepatocellular carcinoma

Cancer therapeutic agents targeting hypoxia-inducible factor-1.

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The discovery of hypoxia-inducible factor-1 has led to a rapidly increasing understanding of the molecular mechanism of tumor hypoxia in the past two decades. Today it is generally accepted that HIF-1 plays a pivotal role in the cellular response to tumor hypoxia which represents a major obstacle to

Ischemia but not anoxia evokes vesicular and Ca(2+)-independent glutamate release in the dorsal vagal complex in vitro.

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Whole cell recordings of fura-2 dialyzed vagal neurons of brain stem slices were used to monitor interstitial glutamate accumulation within the dorsal vagal complex. Anoxia produced a sustained outward current (60 pA) and a moderate [Ca(2+)](i) rise (40 nM). These responses were neither mimicked by

Attenuated effects of Neu2000 on hypoxia-induced synaptic activities in a rat hippocampus.

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Neu2000 (NEU; 2-hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino)-benzoic acid), a recently developed derivative of acetylsalicylic acid and sulfasalazine, potently protects against neuronal cell death following ischemic brain injury by antagonizing NMDA receptor-mediated neuronal

Hypoxia attenuate ionic transport in the isolated gill epithelium of Carcinus maenas.

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The gills are osmorespiratory organs of aquatic organisms and the prime target of environmentally induced hypoxia. We have studied the impact of severe hypoxia (0.5 mg O₂/L) on the ionic transport across posterior gills of Carcinus maenas acclimated to 12 ppt seawater (DSW). The

Role of Cl- in cerebral vascular tone and expression of Na+-K+-2Cl- co-transporter after neonatal hypoxia-ischemia.

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Chloride (Cl-) efflux induces depolarization and contraction of vascular smooth muscle cells. In the basilar arteries from the New Zealand white rabbits, the role of Cl- flux in serotonin-induced contraction was demonstrated by (i) inhibition of Na+-K+-2Cl- co-transporter (NKCC1) to decreased Cl-

A novel Ca2+/calmodulin antagonist HBC inhibits angiogenesis and down-regulates hypoxia-inducible factor.

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Recent reports have shown that Ca(2+)/calmodulin (Ca(2+)/CaM) signaling plays a crucial role in angiogenesis. We previously developed a new Ca(2+)/CaM antagonist, HBC (4-{3,5-bis-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-4,5-dihydropyrazol-1-yl}benzoic acid), from a curcumin-based synthetic chemical

ZYZ451 protects cardiomyocytes from hypoxia-induced apoptosis via enhancing MnSOD and STAT3 interaction.

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3,5-dimethoxy-4-(2-amino-3-prop-2-ynylsulfanyl-propionyl)-benzoic acid 4-guanidino-butyl ester (ZYZ451) was found to be an excellent cardio-protective agent in the previous research in our lab. However, its potent therapeutic effects on myocardial infarction and the underlying mechanism remain

A Novel Malate Dehydrogenase 2 Inhibitor Suppresses Hypoxia-Inducible Factor-1 by Regulating Mitochondrial Respiration.

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We previously reported that hypoxia-inducible factor (HIF)-1 inhibitor LW6, an aryloxyacetylamino benzoic acid derivative, inhibits malate dehydrogenase 2 (MDH2) activity during the mitochondrial tricarboxylic acid (TCA) cycle. In this study, we present a novel MDH2 inhibitor compound 7 containing

The Mitochondrial Citrate Carrier (SLC25A1) Sustains Redox Homeostasis and Mitochondrial Metabolism Supporting Radioresistance of Cancer Cells With Tolerance to Cycling Severe Hypoxia.

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Pronounced resistance of lung cancer cells to radiotherapy and chemotherapy is a major barrier to successful treatment. Herein, both tumor hypoxia and the upregulation of the cellular antioxidant defense systems observed during malignant progression can contribute to radioresistance. We recently

Rescue of neurons from ischemic injury by peroxisome proliferator-activated receptor-gamma requires a novel essential cofactor LMO4.

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Activation of peroxisome proliferator-activated receptor-gamma (PPARgamma) signaling after stroke may reduce brain injury, but this effect will depend on the levels of receptor and cofactors. Here, we showed that the direct effect of PPARgamma signaling to protect neurons from ischemic injury

Regulation of proliferation and membrane potential by chloride currents in rat pulmonary artery smooth muscle cells.

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Pulmonary artery smooth muscle cell (PASMC) proliferation contributes to increased pulmonary vascular resistance and pulmonary hypertension. Because proliferation depends on membrane potential (V(m)) and because V(m) is, in part, determined by Cl(-) currents (I(Cl)), we examined the effects of I(Cl)

[Cl-]i modulation of Ca2+-regulated exocytosis in ACh-stimulated antral mucous cells of guinea pig.

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The effects of intracellular Cl- concentration ([Cl-]i) on acetylcholine (ACh)-stimulated exocytosis were studied in guinea pig antral mucous cells by video microscopy. ACh activated Ca2+-regulated exocytosis (an initial phase followed by a sustained phase). Bumetanide (20 microM) or a Cl- -free

Pharmacophore-based 3D-QSAR of HIF-1 inhibitors.

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(Aryloxyamino)benzoic acids and nicotinic/isonicotinic acids represent an important new class of small molecules that inhibit the activation of hypoxia-inducible factor (HIF)-1. In order to understand the factors affecting inhibitory potency of HIF-1 inhibitors, 3 dimensional-quantitative structure

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