Apigenin Inhibits Proliferation, Migration, and Invasion of Human Tongue Carcinoma Tca8113 Cells Through Regulating the MAPK Signaling Pathways.

OBJECTIVE: This study aimed to examine the effects of apigenin (API) on the proliferation, migration, and invasion of human tongue squamous cell carcinoma Tca8113 cells and explore its probable mechanisms. METHODS: After treating Tca8113 cells with API, the cell proliferation, migration, and invasive capacities were identified by tetrazolium salt colorimetry (MTT) assay, cell scratch test, and Transwell chamber test. Cellular immunofluorescence staining was used to localize mitogen-activated protein kinase 1 (MAPK1) and extracellular regulated protein kinase (ERK) 1/2 proteins. Western blot was used to detect the variations of the related protein expression levels. RESULTS: 1)Through the MTT assay, API significantly inhibited cell proliferation (P<0.01). 2) In the cell scratch test, the distance of lateral migration after the API treatment was significantly shorter compared to the control group (P<0.01). 3) The invasion rate in the lower chamber of the Transwell chamber was lower in the API group (P<0.01). 4) Cellular immunofluorescence staining presented that the total-MEKK1 was localized in the cytoplasm, p-MEKK1 was localized in the nuclear membrane and cytoplasm, and p-ERK1/2 was localized in the cytoplasm and nucleus. ⑤ After API was applied to cells, the expressions of p-MEKK1 and p-ERK1/2 proteins significantly reduced (P<0.01). CONCLUSION: Apigenin (API) significantly inhibits the proliferation, migration, and invasion of Tca8113 cells and its mechanism may be associated with the MAPK signaling pathway.

TGF-ß downregulation overcomes gemcitabine resistance in oral squamous cell carcinoma.

OBJECTIVE: The aim of this study was to explore the mechanisms by which oral cancer acquires resistance to gemcitabine. METHODS: Oral squamous cell carcinoma (OSCC) cells were treated with gemcitabine upon infection or with a lentivirus harboring short hairpin RNA (shRNA) targeted to transforming growth factor-ß (TGF-ß). Then, Western blot, ELISA, migration assay, MTT assay, and animal experiments were used to explore the mechanism of resistance to gemcitabine treatment. RESULTS: After the treatment of non-transfected cells with gemcitabine, NF-κB and AKT activities were increased, which may have induced the OSCC resistance to gemcitabine. Then, we found that TGF-ß downregulation effectively reduced NF-κB and AKT phosphorylation levels after the administration of gemcitabine and increased the OSCC sensitivity to gemcitabine, resulting in cell death and the blunting of OSCC resistance to gemcitabine. The EMT was also reduced by TGF-ß downregulation combined with gemcitabine treatment. CONCLUSION: Cellular levels of TGF-ß constitute an important factor in gemcitabine resistance and TGF-ß silencing might represent a novel and potent strategy for overcoming OSCC resistance to gemcitabine.

Correlation Between PPARGC1A Gene Rs8192678 G>A Polymorphism and Susceptibility To Type-2 Diabetes.

OBJECTIVE: To systematically investigate the correlation between the G>A polymorphism of the peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A or PGC-1alpha) gene rs8192678 locus and the susceptibility to type-2 diabetes mellitus (T2DM). METHODS: The inclusion and exclusion criteria and retrieval strategies of original literatures were formulated. Then, subjects and free words "PPARGC1A","gene polymorphism", and "T2DM" were retrieved from the PubMed, EMBASE, and Cochrane Library databases. Case-control studies on the G>A polymorphism of the PPARGC1A gene rs8192678 locus and susceptibility to T2DM were included for the meta-analysis. RESULTS: The number of cases in the T2DM group and control group was 5,607 and 7,596, respectively. The meta-analysis revealed that the PPARGC1A gene rs8192678 locus G>A polymorphism is associated with susceptibility to T2DM. There are differences in each group of genetic models, of which three groups of genetic models are highly significant. In the allele model, OR=1.249, 95% CI: 1.099-1.419, and P=0.001. In the dominant inheritance model, OR=1.364, 95% CI: 1.152-1.614, and P=0.000. In the additive inheritance model, OR=0.828, 95% CI: 0.726-0.945, and P=0.005. And one group is significant, in the recessive inheritance model, OR=1.187, 95% CI: 1.021-1.381, and P=0.026. CONCLUSION: In Western Asian, South Asian, European and African populations, the A allele of the PPARGC1A gene rs8192678 locus may be one of the risk factors for T2DM.

Association of sLR11 gene polymorphism with T2DM and carotid atherosclerosis.

OBJECTIVE: To investigate the association of single nucleotide polymorphisms (SNPs) of soluble low-density lipoprotein receptor 11 (sLR11) genes with type-2 diabetes mellitus (T2DM) and carotid atherosclerosis (CAS) in Korean and Han nationalities in the Yanbian area. METHODS: 530 T2DM patients were divided into two groups according to the intima-media thickness (IMT) of the carotid artery: CAS group (n= 256, T2DM patients with carotid artery IMT ⩾ 1.0 mm and plaque) and non-CAS group (NCAS group, n= 274, T2DM patients with carotid IMT < 1.0 mm). IMT and plaque were measured by color Doppler ultrasound. SNP typing and sequencing were performed by PCR-LDR. RESULTS: 1. Allele frequency and genotype frequency distribution results: Differences in genotype and allele frequency distribution between the CAS and NGT groups, the NCAS and NGT groups, and the CAS and NCAS groups were not statistically significant (P> 0.05). The dominant and recessive modes were analyzed, but the difference in genotype frequency among these three groups was not statistically significant (P> 0.05). Differences in genotype frequency distribution between Korean and Han populations in all three groups were not statistically significant (P> 0.05). 2. Correlation analysis with clinical indicators: LDL-C levels in TT and AT patients in the CAS group were significantly higher than those in AA patients (P> 0.05), representing the dominant mode of inheritance.. CONCLUSION: This study is the first to determine that the sLR11 gene rs3824968 polymorphic of factor T may increase the risk of CAS in T2DM patients by regulating the concentration of LDL-C, showing the dominant mode of inheritance.

[Study of the association between SNP rs7903146(C/T) in TCF7L2 and metabolic syndrome in Chinese Korean and Han populations from Yanbian].

OBJECTIVE: To assess the association between a rs7903146(C/T) polymorphism of TCF7L2 gene and metabolic syndrome (MS), plasma lipoprotein, and plasma adiponectin (PA) in Chinese Korean and Han populations from Yanbian region. METHODS: Polymerase chain reaction and DNA sequencing were used to determine the genotype of rs7903146 in 310 Chinese Korean (190 in case group and 120 in control group) and 344 Chinese Han (255 in case group and 89 in control group). ELIAS was used to test serum insulin (INS) and PA. RESULTS: The frequency of T allele was higher in ethnic Han compared with ethnic Koreans (0.022 vs. 0.008), lower than that of Europeans (0.279) and Africans (0.257), but similar to those of Beijing Chinese and Japanese. For ethnic Korean Chinese, the frequencies of TT and CT genotypes as well as the T allele in patients with EH were significantly higher than those of the control group (P< 0.01), which also showed an increasing trend for both MS and T2DM groups (P=0.09 and P=0.07, respectively). By contrast, for Chinese Han, the frequencies of genotypes and particular allele in patients with MS, T2DM and EH showed no significant difference from those of the control group. For T2DM, EH, and control groups, PA level of individuals with CT or TT genotypes was significantly higher compared with that of the CC genotype (P< 0.05). The TC and LDL-C levels were significantly higher in T2DM, MS and EH groups compared with those of the control group. The PA level was lower in MS group compared with the control group. CONCLUSION: The T allele of SNP rs7903146 of TCF7L2 gene may be a risk factor for EH in Chinese Korean population from Yanbian region. The T allele also affects the PA level; lower PA is a risk factor for MS. The rs7903146 polymorphism showed a racial and ethnic difference.

[Association between single nucleotide polymorphisms (SNPs) at the promoter of adiponectin gene and essential hypertension in Chinese Korean and Han of Yanbian region].

To investigate the association between the single nucleotide polymorphisms (SNPs) in adiponectin gene promoter and essential hypertension (EH) in Chinese Korean and Han of Yanbian area, 220 EH patients and 268 normotensive control individuals were enrolled. PCR and direct DNA sequencing were used to determine the -11426A>G (rs16861194), -11391G>A (rs17300539), -11377C>G (rs62620185), -11156insCA (rs60806105), and -11043C>T (rs76786086) SNPs in the promoter region of adiponectin gene. Total cholesterol (TC), the triglyceride (TG), fasting plasma glucose (FPG), low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C) levels were examined by oxi-dase method. The plasma adiponectin and insulin were measured by enzyme linked immunosorbent assay (ELISA). The results showed that: (1) SNPs of -11426A>G, -11377C>G, and -11156insCA were found and in Hardy-Weinberg equilib-rium (P>0.05), but not the case in -11391G>A and -11043C>T. (2) -11426A>G and -11156insCA were perfectly in link-age disequilibrium (D'=1; r2=1). (3) The allele G frequency of -11426A>G polymorphism in Chinese Korean (21.10%) was significantly higher than that in Chinese Han (12.50%), and also higher in EH group than in the control group of Chinese Han. The genotype and allele frequencies of -11377C>G showed no significant difference between the two groups ob-served. (4) The haplotype -11426G -11377C frequency in EH of Chinese Han was higher than in the control group (P<0.05). (5) The EH showed lower plasma adiponectin level compared with the control group (P<0.001) in both Chinese Korean and Han. Our results indicate that: (1) the perfect linkage disequilibrium of -11426A>G and -11156insCA is first reported, and the SNP of -11426A>G is associated with Chinese Han and Korean. (2) -11426 G and -11426G -11377C are risk factor and risk haplotype in Yanbian Chinese Han, but not in Chinese-Korean. (3) The lower hypoadiponectinemia is the important risk factors for EH in Chinese Korean and Han of Yanbian area. (4) There is no relationship between -11426A>G polymorphism and the plasma adiponectin level.

[The research of basic medical education with clinical practice and culturing of discovering and creative ability for students].

In order to explore the educational model of combined research aidding basic medical education and clinical practice, the educational form of combined research, teaching and clinical practice was adopted and brought into the education of medical genetics for medical students. The consequence of five-year educational practice has revealed that the educational effects and quality have been obviously increased, and the deeply activated studying initiative, self-studying ability, ability of cooperation, discovering and creative ability have been achieved in culturing practical general medical students with in-depth basic knowledge, great ability and high quality.