• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3667-3671
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• 2015

Invasion and metastasis is the major cause of tumor recurrence, difficulty for cure and low survival rate. Excavating key transcription factors, which can regulate tumor invasion and metastasis, are crucial to the development of therapeutic strategies for cancers. PU.1 is a master hematopoietic transcription factor and a vital regulator in life. Here, we report that, compared to adjacent non-cancerous tissues, expression of PU.1 mRNA in metastatic hepatocellular carcinoma (HCC), but not primary HCC, was significantly down-regulated. In addition, levels of PU.1 mRNA in metastatic hepatoma cell lines MHCC97L and MHCC97H were much lower than in non-metastatic Hep3B cells. Transwell invasion assays after PU.1 siRNA transfection showed that the invasion of hepatoma cell lines was increased markedly by PU.1 knockdown. Oppositely, overexpression of PU.1 suppressed the invasion of these cells. However, knockdown and overexpression of PU.1 did not influence proliferation. Finally, we tried to explore the potential mechanism of PU.1 suppressing hepatoma cell invasion. ChIP-qPCR analysis showed that PU.1 exhibited a high binding capacity with miR-615-5p promoter sequence. Overexpression of PU.1 caused a dramatic increase of pri-, pre- and mature miR-615-5p, as well as a marked decrease of miR-615-5p target gene IGF2. These data indicate that PU.1 inhibits invasion of human HCC through promoting miR-615-5p and suppressing IGF2. These findings improve our understanding of PU.1 regulatory roles and provided a potential target for metastatic HCC diagnosis and therapy.

• Journal of Microbiology and Biotechnology
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• 제24권3호
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• pp.363-370
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• 2014

Campylobacter jejuni is a prevalent foodborne pathogen worldwide. Human infection by C. jejuni primarily arises from contaminated poultry meats. Genes expressed in vivo may play an important role in the pathogenicity of C. jejuni. We applied an immunoscreening method, in vivo-induced antigen technology (IVIAT), to identify in vivo-induced genes during human infection by C. jejuni. An inducible expression library of genomic proteins was constructed from sequenced C. jejuni NCTC 11168 and was then screened using adsorbed, pooled human sera obtained from clinical patients. We successfully identified 24 unique genes expressed in vivo. These genes were implicated in metabolism, molecular biosynthesis, genetic information processing, transport, and other processes. We selected six genes with different functions to compare their expression levels in vivo and in vitro using real-time RT-PCR. The results showed that the selected six genes were significantly upregulated in vivo but not in vitro. In short, these identified in vivo-induced genes may contribute to human infection of C. jejuni, some of which may be meaningful vaccine candidate antigens or diagnosis serologic markers for campylobacteriosis. IVIAT may present a significant and efficient method for understanding the pathogenicity mechanism of Campylobacter and for finding targets for its prevention and control.

• Journal of Ginseng Research
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• 제47권6호
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• pp.755-765
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• 2023

Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca²⁺ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca²⁺ ([Ca²⁺]_i) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca²⁺]_i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca²⁺]_i against MI injury in neonatal rat cardiomyocytes and a rat model. Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca²⁺]_i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured. Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca²⁺ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG. Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca²⁺]_i.

• Journal of Nutrition and Health
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• 제40권7호
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• pp.593-600
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• 2007

Recent studies described the ${\varepsilon}4$ allele of apoE confers a two-to fourfold increased risk for late-onset Alzheimer#s disease (LOAD), but LOAD pathology does not all fit neatly around apo E. Therefore, the goal of this study was to find the association between Alzheimer and apo E4 genotype in the 107 elderly between 50 to 64 years old who visited to FHWC of Sungshin Women#s University. We conducted the questionnaire survey (general & 24 hr dietary recall), anthropometerics (BP, waist & BMI) and blood biochemistry (FBS & lipid profiles). LDL-c and HOMA-IR were calculated by Friedwald#s and Matthew#s formulas. The apo E genotyping was performed by PCR-RFLP method and subjects were divided into three allele groups (${\varepsilon}3$; wild, ${\varepsilon}2$ & ${\varepsilon}4;$ mutants). The apo E allele frequencies were 7.0% for the ${\varepsilon}2$, 83.6% for the ${\varepsilon}3$ and 9.3% for the ${\varepsilon}4$. In comparison with biochemistry characteristics by apo E genotype, FBS was significantly higher in ${\varepsilon}4(129.2{\pm}6.8)$ than that in the others (${\varepsilon}2$: $117{\pm}7.4$, ${\varepsilon}3$: $107.3{\pm}2.2)$ (p<0.01). More than forty percents of ${\varepsilon}4$ group shown the dyslipidemia [high TG (>150mg/dl) & low HDL (<40 mg/dl:male or <50 mg/dl: female)]. The cytokines levels such as IL-1 ${\beta}$, IL-6 and $TNF-{\alpha}$ were not different among three apoE alleles. After the adjusting sex, age & dietary fiber, LDL-c level was siginificantly higher in ${\varepsilon}4$ ($108.3{\pm}7.7$) than that in ${\varepsilon}2$ ($100.4{\pm}8.4$) (p<0.05). According to food intake and the recipe on the basis of 24 hr dietary recall, the elder]y with ${\varepsilon}4$ allele took higher intake frequency of the light -colored vegetable (radish, onion & cabbage) and pan-fried foods (sauteed beef and vegetables, stir-fried vienna with vegetables) than the others. We knew that the elderly with ${\varepsilon}4$ allele had been restricted the calories intakes with high dietary fiber (33.6+2.5 g/d) to maintain the normal level of FBS and LDL-c. On next study, the prevalence of Alzheimer#s disease in this population who has ${\varepsilon}4$ allele on the condition of calories restriction will be continually follow-up.