Aldo-keto reductases-mediated cytotoxicity of 2-deoxyglucose: A novel anticancer mechanism.

2-Deoxyglucose (2DG) is a non-metabolizable glucose analog currently in clinical trials to determine its efficacy in enhancing the therapeutic effects of radiotherapy and chemotherapy of several types of cancers. It is thought to preferentially kill cancer cells by inhibiting glycolysis because cancer cells are more dependent on glycolysis for their energy needs than normal cells. However, we found that the toxicity of 2DG in cancer cells is mediated by the enzymatic activities of AKR1B1 and/or AKR1B10 (AKR1Bs), which are often overexpressed in cancer cells.

Extract of Zuojin Pill ([characters: see text]) induces apoptosis of SGC-7901 cells via mitochondria-dependent pathway.

Objective: To observe the effects of water extract of Zuojin Pill ([characters: see text], ZJP) on inhibiting the growth of human gastric cancer cell line SGC-7901 and its potential mechanism.

Methods: Effects of ZJP on SGC-7901 cells growth were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, cell apoptosis and cell cycle were determined by flow cytometry, and apoptosis induction was detected by means of DNA gel electrophoresis. The cellular mechanism of drug-induced cell death was unraveled by assaying oxidative injury level of SGC-7901 cell, mitochondrial membrane potentials, expression of apoptosis-related genes, such as B cell lymphoma/lewkmia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cleaved caspase-3 and caspase-9.

Neurokinin-3 peptide instead of neurokinin-1 synergistically exacerbates kainic acid-inducing degeneration of neurons in the substantia nigra of mice.

Neurokinin peptides neurokinin-1 (NK1), neurokinin-3 (NK3), and related receptors are abundantly distributed in the substantia nigra (SN) and evidenced by their possible roles in the Parkinson's disease. Differential intervention roles of NK3 on kainic acid (KA)-induced neuronal injury in the SN of mice were thus in vitro and in vivo studied by Fluoro-Jade C (FJC) staining, immunohistochemistry to tyrosine hydroxylase (TH) or phospho-NMDA receptor, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. It revealed that (i) in contrast to protective effect of NK1 agonist septide that reduced FJC-positive degenerative neurons and lesion volume insulted by KA, NK3 agonist senktide significantly increased FJC-positive ones and lesion volume, and this effect was sufficiently reversed by NK3 antagonist SB218795; (ii) similarly, senktide reduced TH-positive neurons and this effect was antagonized by SB218795, but septide increased TH-positive ones; (iii) mechanistic observation showed differential influences of NK1 and NK3 agonists on phosphorylated-NMDA receptor subunit 1 (phospho-NMDAR1) and glial fibrillary acidic protein-expressing astrocytes, i.

Reactive astrocytes as potential manipulation targets in novel cell replacement therapy of Parkinson's disease.

Parkinson' disease (PD) is a most common and debilitating degenerative disease resulted from massive loss of dopamine neurons in the substantia nigra pars compacta, which is characterized by severe motor symptoms of tremor, bradykinesia, rigidity and postural instability. Protection of nigral dopamine neurons from progressive degenerative death and cell replacement of novel dopamine neurons are hopeful strategies against PD in humans. The reactive astrocytes or functional activation of astrocytes abundantly occurred in brain insults including trauma, ischemia, and 6-OHDA or MPTP-treated PD animal models.

[Changes in cAMP and cGMP levels in neonatal rat histaminergic neurons of tuberomammillary nucleus following 48-hour morphine exposure and effects of sinomenine intervention].

Objective: To explore the effects of long-term morphine exposure on cAMP and cGMP levels in primary cultured tuberomammillary nucleus (TM) neurons of neonatal rats and the effects of sinomenine on morphine-dependent TM cells.

Methods: TM neurons after a 7-day primary culture were further cultured in the medium containing 100 micromol/L morphine for 48 h to prepare the cell model of morphine dependence. Serial doses of histamine or sinomenine were administered 30 min naloxone treatment, the cAMP and cGMP levels of the TM cells were determined by enzyme immunoassay.

[Primary culture of histaminergic neurons in neonatal rat hypothalamus tuberomammillary nucleus].

Objective: To establish primary cell culture conditions for tuberomammillary nucleus (TM) histaminergic neurons of neonatal rats.

Methods: The tuberomammillary nucleus was dissected from the posterior part of the hypothalamus of neonatal rats, and neurobasal medium supplemented with B27 was used for the primary cell culture. The cultured neurons were identified by immunocytochemical method (ICC).