Ribbon-type antisense oligonucleotide to TGF-beta1(TGF-beta1 RiAS) was designed and tested to prevent or resolve the fibrotic changes induced by CCl4 injection. When Hepa1c1c7 cells were transfected with TGF-beta1 RiAS, the level of TGF-beta1 mRNA was effectively reduced. TGF-beta1 RiAS, mismatched RiAS, and normal saline were each injected to mice via tail veins. When examined for the biochemical effects on the liver, TGF-beta1 mRNA levels were significantly reduced only in the TGF-beta1 RiAS-treated group. The results of immunohistochemical studies showed that TGF-beta1 RiAS prevented the accumulation of collagen and alpha-smooth muscle actin, but could not resolve established fibrosis. These results indicate that ribbon antisense to TGF-beta1 with efficient uptake can effectively prevent fibrosis of the liver.
Actins ; Animals ; Collagen ; Fibrosis ; Liver ; Liver Cirrhosis ; Mice ; Muscles ; RNA, Messenger ; Transforming Growth Factor beta1 ; Veins

No abstract available.
Blood Platelets* ; Electrophoresis, Polyacrylamide Gel* ; Flow Cytometry* ; Membrane Glycoproteins* ; Membranes* ; Thrombasthenia*

The purpose of the present study was to determine whether chronic high-fat diet (HF) induces insulin resistance independently of obesity. We randomly divided 40 rats into two groups and fed them either with a HF or with a high-carbohydrate diet (HC) for 8 weeks. Whole body glucose disappearance rate (Rd) was measured using a euglycemic hyperinsulinemic clamp. Firstly, we defined whether insulin resistance by HF was associated with obesity. Plasma glucose and triglyceride concentrations were significantly increased in HF. Rd was decreased (10.6+/-0.2 vs. 9.1+/-0.2 mg/kg/min in HC and HF, respectively) and the hepatic glucose output rate (HGO) was increased in HF (2.2+/-0.3 vs. 4.5+/-0.2 mg/kg/min in HC and HF, respectively). Rd was significantly correlated with %VF (p<0.01). These results implicate that visceral obesity is associated with insulin resistance induced by HF. In addition, to define whether dietary fat induces insulin resistance regardless of visceral obesity, we compared Rd and HGO between groups 1) after matching %VF in both groups and 2) using an ANCOVA to adjust for %VF. After matching %VF, Rd in HF was significantly decreased by 14% (p<0.001) and HGO was significantly increased by 110% (p<0.001). Furthermore, statistical analyses using an ANCOVA also showed Rd for HF was significantly decreased even after adjusting %VF. In conclusion, we suggest that dietary fat per se could induce insulin resistance in rats fed with chronic HF independently of obesity.
Adipose Tissue/*pathology ; Animal ; Dietary Carbohydrates/administration &age ; Dietary Fats/*administration &age ; Fatty Acids, Nonesterified/metabolism ; Female ; *Insulin Resistance ; Obesity/etiology ; Rats ; Rats, Sprague-Dawley ; Viscera

No abstract available.

OBJECTIVE: The aim of this study is to find out the genes which are related to ovarian cancer cell growth using large circular antisense library. METHODS: Clones for antisense library were uni-directionally sub-cloned into pBS SK (-) vector. LC-antisense molecules were then purified from the culture supernatants of the bacterial competent cells superinfected with M13K07 helper bacteriophages. The LC-antisense library to 240 unigene clone was constructed and utilized in the identification of genes functionally involved in the growth of ovarian cancer cells. RESULTS: The 17 numbers out of the 240 numbers of the antisense library exerted a marked inhibitory effect on the growth of SK-OV 3. CONCLUSION: The putative functional categorization of each gene was then conducted via public databases. These candidates may be used as target genes for drug development or adjuvant of conventional chemotherapeutic drugs.
Bacteriophages ; Clone Cells ; Estrone ; Gene Targeting ; Genetic Therapy ; Ovarian Neoplasms

No abstract available.
Factor VII Deficiency* ; Factor VII*

The purpose of this study was to discern the critical point in skeletal muscle fatty acid oxidation by changing plasma free fatty acids (FFA) level in rat. In the study, 3 key steps in lipid oxidation were examined after changing plasma FFA level by acipimox. The rates of both palmitate and palmitoyl- carnitine oxidation were decreased by decrease of plasma FFA level, however, carnitine palmitoyl transferase (CPT) 1 activity was not changed, suggesting CPT1 activity may not be involved in the fatty acid oxidation at the early phase of plasma FFA change. In the fasted rats, beta-hydroxy acyl-CoA dehydrogenase (beta-HAD) activity was depressed to a similar extent as palmitate oxidation by a decrease of plasma FFA level. This suggested that beta-oxidation might be an important process to regulate fatty acid oxidation at the early period of plasma FFA change. Citrate synthase activity was not altered by the change of plasma FFA level. In conclusion, the critical step in fatty acids oxidation of skeletal muscles by the change of plasma FFA level by acipimox in fasting rats might be the beta-oxidation step rather than CPT1 and TCA cycle pathways.
Acyl-CoA Dehydrogenase ; Animals ; Carnitine ; Citrate (si)-Synthase ; Fasting ; Fatty Acids ; Fatty Acids, Nonesterified* ; Muscle, Skeletal ; Plasma* ; Rats* ; Transferases

We examined the effect of leptin on the insulin resistance in skeletal muscles by measuring the glucose transport. Male Wistar rats were fed with chow or high-fat diets for 30 days. Three days before sacrifice, high-fat fed rats were subcutaneously injected with leptin (1 mg/kg body weight) for 3 days. The glucose transports in the epitrochlearis and soleus muscle were not different among the experimental groups under basal state, however these were decreased significantly in the high fat-diet rats under insulin-stimulation (P< 0.01). Leptin treatment recovered the decreased glucose transport in the epitrochlearis (P< 0.05) and soleus (p=0.08). Triglyceride concentration in the soleus muscle was increased significantly in the high fat-fed rats, compared to chow diet rats (P< 0.01), and it was decreased significantly by leptin treatment (P< 0.01). The glucose transport was measured under basal and 60microU/ml of insulin with or without 50 ng/ml of leptin. Leptin had no direct stimulatory effect on glucose transport under both basal and insulin-stimulated conditions in vitro. These results demonstrate that leptin injection to high fat diet fed rats recovered impaired insulin responsiveness of the skeletal muscles and muscle triglyceride concentration. However, there was no direct stimulatory effect of leptin on insulin sensitivity of the skeletal muscle in vitro.
Animals ; Diet ; Diet, High-Fat* ; Glucose ; Humans ; Insulin Resistance* ; Insulin* ; Leptin* ; Male ; Muscle, Skeletal* ; Rats* ; Rats, Wistar ; Triglycerides

Objectives: This study investigates the association between short-term exposure to air pollutants and panic attacks requiring emergency department (ED) visits. Methods: We identified 1926 patients who visited EDs in Seoul with panic attacks as the primary cause during the period from 2008 to 2014. We estimated short-term exposure to particles <2.5 μm (PM2.5), particles <10 μm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO). We applied a time-stratified case-crossover study design and conducted a conditional logistic regression analysis to assess the association between air pollutants levels and ED visits due to panic attacks. Results: Increasing O3 concentration was significantly associated with an increased risk of panic attacks requiring ED visits (odds ratio: 1.15; 95% confidence interval: 1.04–1.27) on the same day of exposure. This association was robust to the sensitivity analysis using two pollutant models. Conclusion Our results show that short-term exposure to elevated O3 concentration is associated with the exacerbation of panic attacks. This finding strongly suggests the detrimental effects of O3 on major public health problems and provides insights for further research to investigate the causal associations between air pollution and poor mental health.

Objectives: This study investigates the association between short-term exposure to air pollutants and panic attacks requiring emergency department (ED) visits. Methods: We identified 1926 patients who visited EDs in Seoul with panic attacks as the primary cause during the period from 2008 to 2014. We estimated short-term exposure to particles <2.5 μm (PM2.5), particles <10 μm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO). We applied a time-stratified case-crossover study design and conducted a conditional logistic regression analysis to assess the association between air pollutants levels and ED visits due to panic attacks. Results: Increasing O3 concentration was significantly associated with an increased risk of panic attacks requiring ED visits (odds ratio: 1.15; 95% confidence interval: 1.04–1.27) on the same day of exposure. This association was robust to the sensitivity analysis using two pollutant models. Conclusion Our results show that short-term exposure to elevated O3 concentration is associated with the exacerbation of panic attacks. This finding strongly suggests the detrimental effects of O3 on major public health problems and provides insights for further research to investigate the causal associations between air pollution and poor mental health.