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Article in English | WPRIM | ID: wpr-764368


BACKGROUND AND PURPOSE: It is essential to develop a reliable predictive serum biomarker for Parkinson's disease (PD). The accumulation of alpha-synuclein (αSyn) and up-regulated expression of Rab35 participate in the etiology of PD. The purpose of this investigation was to determine whether the combined assessment of serum αSyn and Rab35 is a useful predictive biomarker for PD. METHODS: Serum levels of αSyn or Rab35 were determined in serum samples from 59 sporadic PD patients, 19 progressive supranuclear palsy (PSP) patients, 20 multiple system atrophy (MSA) patients, and 60 normal controls (NC). Receiver operating characteristics (ROC) curves were calculated to determine the diagnostic accuracy of αSyn or/and Rab35 in discriminating PD patients from NC or atypical parkinsonian patients. RESULTS: The levels of αSyn and Rab35 were increased in PD patients. The serum level of Rab35 was positively correlated with that of αSyn in PD patients. Compared to analyzing αSyn or Rab35 alone, the combined analysis of αSyn and Rab35 produced a larger area under the ROC curve and performed better in discriminating PD patients from NC, MSA patients, or PSP patients. When age was dichotomized at 55, 60, 65, or 70 years, the combined assessment of αSyn and Rab35 for classifying PD was better in the group below the cutoff age than in the group above the cutoff age. CONCLUSIONS: Combined assessment of serum αSyn and Rab35 is a better biomarker for discriminating PD patients from NC or atypical parkinsonian patients, and is a useful predictive biomarker for younger sporadic PD patients.

alpha-Synuclein , Humans , Multiple System Atrophy , Parkinson Disease , ROC Curve , Supranuclear Palsy, Progressive
Intestinal Research ; : 174-181, 2017.
Article in English | WPRIM | ID: wpr-117645


BACKGROUND/AIMS: Parthenolide (PT), a principle component derived from feverfew (Tanacetum parthenium), is a promising anticancer agent and has been shown to promote apoptotic cell death in various cancer cells. In this study, we focused on its functional role in apoptosis, migration, and invasion of human colorectal cancer (CRC) cells. METHODS: SW620 cells were employed as representative human CRC cells. We performed the MTT assay and cell cycle analysis to measure apoptotic cell death. The wound healing, Transwell migration, and Matrigel invasion assays were performed to investigate the effect of PT on cell migration/invasion. Western blotting was used to establish the signaling pathway of apoptosis and cell migration/invasion. RESULTS: PT exerts antiproliferative effect and induces apoptotic cell death of SW620 cells. In addition, PT prevents cell migration and invasion in a dose-dependent manner. Moreover, PT markedly suppressed migration/invasion-related protein expression, including E-cadherin, β-catenin, vimentin, Snail, cyclooxygenase-2, matrix metalloproteinase-2 (MMP-2), and MMP-9 in SW620 cells. PT also inhibited the expression of antiapoptotic proteins (Bcl-2 and Bcl-xL) and activated apoptosis terminal factor (caspase-3) in a dose-dependent manner. CONCLUSIONS: Our results suggest that PT is a potential novel therapeutic agent for aggressive CRC treatment.

Apoptosis , Blotting, Western , Cadherins , Cell Cycle , Cell Death , Cell Movement , Colorectal Neoplasms , Cyclooxygenase 2 , Humans , Matrix Metalloproteinase 2 , Snails , Tanacetum parthenium , Vimentin , Wound Healing
Intestinal Research ; : 233-241, 2015.
Article in English | WPRIM | ID: wpr-96060


BACKGROUND/AIMS: Balsalazide is an anti-inflammatory drug used in the treatment of inflammatory bowel disease. Balsalazide can reduce inflammatory responses via several mechanisms, including inhibition of nuclear factor-kappaB (NF-kappaB) activity. Parthenolide (PT) inhibits NF-kappaB and exerts promising anticancer effects by promoting apoptosis. The present investigated the antitumor effects of balsalazide, combined with PT, on NF-kappaB in a representative human colorectal carcinoma cell line, HCT116. METHODS: We counted cells and conducted annexin-V assays and cell cycle analysis to measure apoptotic cell death. Western blotting was used investigate the levels of proteins involved in apoptosis. RESULTS: PT and balsalazide produced synergistic anti-proliferative effects and induced apoptotic cell death. The combination of balsalazide and PT markedly suppressed nuclear translocation of the NF-kappaB p65 subunit and the phosphorylation of inhibitor of NF-kappaB. Moreover, PT and balsalazide dramatically enhanced NF-kappaB p65 phosphorylation. Apoptosis, through the mitochondrial pathway, was confirmed by detecting effects on Bcl-2 family members, cytochrome c release, and activation of caspase-3 and -8. CONCLUSIONS: Combination treatment with PT and balsalazide may offer an effective strategy for the induction of apoptosis in HCT116 cells.

Apoptosis , Blotting, Western , Caspase 3 , Cell Cycle , Cell Death , Cell Line , Colorectal Neoplasms , Cytochromes c , HCT116 Cells , Humans , Inflammatory Bowel Diseases , NF-kappa B , Phosphorylation
Article in Chinese | WPRIM | ID: wpr-313813


<p><b>OBJECTIVE</b>To construct Epithelia Membrane Protein 1 gene-deficient in human fetal nucleus pulposus model by lentivirus-mediated RNA interference for building a platform for illustrating the biomechanisms role of EMP-1 during human intervertebral disc degeneration.</p><p><b>METHODS</b>The lentivirus vector with shRNA targeting EMP-1 mRNA was transected into 293FT cells by liposome. Then the lentivirus supernatant was obtained and used for infecting human fetal nucleus pulposus. The expression of GFP was observed under fluorescence microscope after 48 h. The viral particles were collected at 72 h after transfection. The efficacy of gene interference was tested by Western blot and Real-time RT-PCR. Analysis the results of the fluorescent microscope scenes and get the average values of EMP-1/GAPDH by detected the interference efficiency of various interference DNA sequences with western blot and semi quantitative RT-PCR methods.</p><p><b>RESULTS</b>The lentivirns with high titer were obtained and the EMP-1 gene deficient cell strains were obtained. Semi quantitative RT-PCR and Western blot proved the average values of EMP-1/GAPDH decreased from 0.46 to 0.32 and 0.5 to 0.25 (P < 0.01).</p><p><b>CONCLUSION</b>Lentivirus packaging technology can be mastered skillfully. EMP-1 gene-deficient cell models are successfully established.</p>

Fetus , HEK293 Cells , Humans , Intervertebral Disc , Metabolism , Lentivirus , Genetics , Neoplasm Proteins , Genetics , RNA Interference , Receptors, Cell Surface , Genetics , Transfection