Expression and Function of Long Non-coding RNA CASC19 in Colorectal Cancer.

Objective To investigate the expression, function and significance of long non-coding RNA (lncRNA) CASC19 in colorectal cancer (CRC). Methods Real-time quantitative polymerase chain reaction was employed to determine the expression of CASC19 in 40 paired samples from CRC surgical specimens and 5 CRC cell lines. The correlations of CASC19 expression with clinicopathologic parameters were analyzed. Transwell assay was applied to detect the migration ability of CRC cells after the CASC19 expression was knocked down by small interfering RNA. Results The expression of CASC19 in colorectal cancer was significantly higher than those in adjacent normal mucosa tissues (t=5.527, P<0.000 1) and was associated with metastasis (P=0.044). Knockdown of CASC19 expression in CRC inhibited the migration ability of CRC in vitro. Conclusions The expression of CASC19 increases in CRC. CASC19 expression is not associated with age, gender, or tumor site/differentiation but with tumor size, lymph node metastasis, and distant metastasis, suggesting high CASC19 expression may promote CRC metastasis.

[Peoniflorin activates Nrf2/ARE pathway to alleviate the Abeta(1-42)-induced hippocampal neuron injury in rats].

This study was to investigate the effect of peoniflorin on the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream signal molecules in the hippocampus of Alzheimer's disease (AD) rats for exploring the mechanism of peoniflorin protecting hippocampal neurons. AD model rats were established by bilateral intrahippocampal injection of beta-amyloid(1-42) (Abeta(1-42)) and divided randomly into 3 groups: AD model group, peoniflorin low-dose (15 mg x kg(-1)) group and peoniflorin high-dose (30 mg x kg(-1)) group. The vehicle control rats were given bilateral intrahippocampal injection of solvent with the same volume. After peoniflorin or saline was administered (ip) once daily for 14 days, the hippocampuses of all animals were taken out for measuring the expressions of Nrf2, heme oxygenase-1 (HO-1) and gamma-glutamylcysteine synthethase (gamma-GCS) mRNA by reverse transcription PCR, determining the contents of glutathione (GSH), malondialdehyde (MDA) and carbonyl protein (CP) using colorimetric method, and for assaying the expressions of neuronal apoptosis inhibitory protein (NAIP) and Caspase-3 by immunohistochemical staining method. The results showed that peoniflorin markedly increased the expressions of Nrf2, HO-1 and gamma-GCS mRNA, enhanced the level of GSH and decreased the contents of MDA and CP in the hippocampus, as compared with the model group. Peoniflorin also improved the NAIP expression and reduced the Caspase-3 expression in the hippocampus neurons. In conclusion, peoniflorin protects against the Abeta(1-42)-mediated oxidative stress and hippocampal neuron injury in AD rats by activating the Nrf2/ARE pathway.

[Protective effect of paeonol on neurotoxicity induced by Abeta1-42 and underlying mechanisms].

OBJECTIVE: To investigate the protective effect of paeonol on amyloid beta1-42 (Abeta1-42)-induced neurotoxicity and its mechanism. METHOD: Hippocampal neurons of well-grown newborn SD rats and differentiated SH-SY5Y cell lines were cultured with various concentrations of paeonol (1, 5, 10 micromol x L(-1), respectively) for 6 hours and then incubated with Abeta1-42 oligomer (30 micromol x L(-1)) for 24 hours and 48 hours, respectively. The neuron apoptosis was observed by Heochst33258. Annexin V/PI double stain flow cytometry assay was adopted for determining SH-SY5Y cell apoptosis rate. And the expression of BDNF and Bcl-2 mRNA was detected by RT-PCR. RESULT: Compared with the model group, various concentrations of paeonol (1, 5, 10 micromol x L(-1)) significantly reduced the hippocampal neurons karyopycnosis, decreased the rate of SH-SY5Y cell apoptosis to 22.4%, 18.1% and 16.4%, respectively, and improved the expressions of BDNF and Bcl-2 mRNA. CONCLUSION: Paeonol relieves Abeta1-42 oligomer-induced neuron injury by increasing BDNF and Bcl-2 expressions.

Peoniflorin attentuates Abeta((1-42))-mediated neurotoxicity by regulating calcium homeostasis and ameliorating oxidative stress in hippocampus of rats.

Peoniflorin (PEF), a monoterpene glycoside isolated from the aqueous extract of the dry root of Paeonia, possesses wide pharmacological effects in nervous system. In this study, by using a developed rat model of hippocampal dysfunction induced by intrahippocampal injection of Abeta((1-42)) oligomers, we investigated whether PEF exerted protection against Abeta-induced neurotoxicity. A stereotactic intrahippocampal bilateral injection of Abeta((1-42)) (5 microg per side) was performed in Sprague-Dawley rats (250-280 g). Abeta((1-42))-exposed rats showed remarkable memory impairment in Morris water maze test and neuronal apoptosis by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling in hippocampus. Chronic treatment with PEF (7.5, 15 and 30 mg/(kg day), for 20 days, intraperitoneally) significantly and dose-dependently attenuated cognitive deficit, ameliorated cell apoptosis in Abeta((1-42))-treated rats. The neuroprotective effect of PEF was closely associated with its activities of maintenance of [Ca(2+)](i) homeostasis, increase of reduced glutathione (GSH) content, suppression of NOS activity and nitric oxide (NO) level, decrease of carbonyl protein (CP) and malondialdehyde (MDA) levels. These results suggested that PEF possessed the activity of prevention of the neurotoxicity induced by Abeta((1-42)) and might exert beneficial action for the treatment of Alzheimer's disease (AD).

Paeonol attenuates neurotoxicity and ameliorates cognitive impairment induced by d-galactose in ICR mice.

In the present study, we examined the supplementation of paeonol extracted from Moutan cortex of Paeonia suffruticosa Andrews (MC) or the root of Paeonia lactiflora Pall (PL) on reducing oxidative stress, cognitive impairment and neurotoxicity in d-galactose (D-gal)-induced aging mice. The ICR mice were subcutaneously injected with D-gal (50 mg/(kg day)) for 60 days and administered with paeonol (50, 100 mg/(kg day)) simultaneously. The results showed that paeonol significantly improved the learning and memory ability in Morris water maze test and step-down passive avoidance test in D-gal-treated mice. Further investigation showed that the effect of paeonol on improvement of cognitive deficit was related to its ability to inhibit the biochemical changes in brains of D-gal-treated mice. Paeonol increased acetylcholine (Ach) and glutathione (GSH) levels, restored superoxide dismutase (SOD) and Na(+), K(+)-adenosine triphosphatase (Na(+), K(+)-ATPase) activities, but decreased cholinesterase AChe activity and malondialdehyde (MDA) level in D-gal-treated mice. Furthermore, paeonol ameliorated neuronal damage in both hippocampus and temporal cortex in D-gal-treated mice. These results suggest that paeonol possesses anti-aging efficacy and may have potential in treatment of neurodegenerative diseases.