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1.
Braz J Med Biol Res ; 50(12): e6138, 2017 Oct 02.
Article in English | MEDLINE | ID: mdl-28977119

ABSTRACT

The aim of this study was to investigate the mechanism of propranolol on the regression of hemangiomas. Propranolol-treated hemangioma tissues were collected and the expression of hypoxia inducible factor-1α (HIF-1α) was examined. We also established HIF-1α overexpression and knockdown hemangioma cells, and determined the effects of HIF-1α on the hemangioma cells proliferation, apoptosis, migration and tube formation. Significantly increased HIF-1α level was found in the hemangioma tissues compared to that in normal vascular tissues, whereas propranolol treatment decreased the HIF-1α level in hemangioma tissues in a time- and dose-dependent manner. Moreover, propranolol treatment significantly decreased cell proliferation, migration and tube formation as well as promoted cell apoptosis in HIF-1α overexpression and knockdown hemangioma cells. Propranolol suppressed the cells proliferation, migration and tube formation of hemangioma cells through HIF-1α dependent mechanisms. HIF-1α could serve as a novel target in the treatment of hemangiomas.


Subject(s)
Cell Movement/drug effects , Cell Proliferation/drug effects , Hemangioma/drug therapy , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Propranolol/therapeutic use , Vasodilator Agents/therapeutic use , Apoptosis/drug effects , Hemangioma/metabolism , Humans
2.
Genet Mol Res ; 15(2)2016 Jun 10.
Article in English | MEDLINE | ID: mdl-27323166

ABSTRACT

Mitochondrial DNA mutations that lead to mitochondrial dysfunction have long been proposed to play important roles in the development of pancreatic cancer. Of these, alterations to mitochondrial tRNA genes constitute the largest group. Most recently, a variation at position 12307 in the gene encoding tRNA(Leu(CUN)) has been reported to be associated with this disease. However, the molecular mechanism underlying this relationship remains poorly understood. To assess this association, we evaluated this variant by evolutionary conservation analysis, measurements of allelic frequencies among control subjects, and use of several bioinformatic tools to estimate potential structural and functional alterations. We found this residue to have a high conservation index; however, the presence of the A12307G variation in control subjects revealed by a literature search suggested it to be common in human populations. Moreover, RNAfold results showed that this variant did not alter the secondary structure of tRNA(Leu(CUN)). Through the application of a pathogenicity scoring system, this variant was determined to be a "neutral polymorphism," with a score of only 4 points based on current data. Thus, the contribution of the A12307G variant to pancreatic cancer needs to be addressed in further experimental studies.


Subject(s)
DNA, Mitochondrial/genetics , Genetic Association Studies , Pancreatic Neoplasms/genetics , RNA, Transfer, Leu/genetics , Evolution, Molecular , Genetic Predisposition to Disease , Humans , Mutation , Nucleic Acid Conformation , Pancreatic Neoplasms/pathology , Polymorphism, Single Nucleotide
3.
Genet Mol Res ; 13(3): 6126-34, 2014 Aug 07.
Article in English | MEDLINE | ID: mdl-25117371

ABSTRACT

We examined the influence of the promoter polymorphisms -250G/A (rs2070895) and -514C/T (rs1800588) in the human hepatic lipase (LIPC) gene on dyslipidemia and hypertensive disorders complicating pregnancy (HDCP) in a Chinese population. Clinically defined HDCP patients (N = 321) and healthy pregnant women (N = 331) were recruited and genotyped using polymerase chain reaction-restriction fragment length polymorphism for the two LIPC single nucleotide polymorphisms (SNPs). The results showed significant relationships between HDCP and triglycerides, apolipoprotein A1, and high-density lipoprotein cholesterol (P < 0.05), which confirmed that HDCP was accompanied by dyslipidemia. The results also demonstrated that in gestational hypertension (GH) patients, both total cholesterol (TC) and systolic blood pressure (SBP) levels were related to the two SNPs (P ≤ 0.004), although no significant association was found between HDCP and LIPC genotypes or alleles. Significant linkage disequilibrium of the two SNPs was found in both HDCP patients (R(2) = 0.867) and controls (R(2) = 0.91). Body mass index (BMI) was associated with -250G/A in women with mild preeclampsia (MPE) (P = 0.01). Carriers of the mutant homozygote -250AA genotype presented higher BMI in the MPE group. In conclusion, the LIPC -250G/A and -514C/T variants influenced TC and SBP levels in GH patients and the BMI level in the MPE group, although there was no evidence to validate an association between HDCP and LIPC allele, genotype, or haplotype frequencies.


Subject(s)
Asian People/genetics , Genetic Association Studies , Hypertension, Pregnancy-Induced/genetics , Lipase/genetics , Polymorphism, Single Nucleotide , Adult , Alleles , Blood Pressure , Case-Control Studies , China , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Hypertension, Pregnancy-Induced/diagnosis , Lipids/blood , Lipoproteins/blood , Pregnancy , Risk
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