The small intestine has been called as a dark continent of digestive tract and it had been very difficult to diagnose or treat the disease of small intestine. However recent technological development including video capsule endoscopy or balloon-assisted endoscopy has made us to aware the various diseases of small intestine. By using capsule endoscopy, many researchers reported that more than 70% of patients treated continuously with non-steroidal anti-inflammatory drugs (NSAID) exhibit the mucosal damage of small intestine. In some cases, NSAID not only causes mucosal damage but also results in life threatening bleeding from small intestine, which had not been prevented or cured by gastro-protective drug or anti-gastric acid secretion drug administration. Therefore to investigate and identify the effective drug that protects small intestine from mucosal damage is urgently expected. In spite of extensive investigation in clinical field, only a few drugs such as misoprostol, a synthetic prostaglandin E1 analogue, has been reported as an effective one but is not satisfactory enough to fulfill the requirement of patients who suffer from NSAID-induced mucosal damage of small intestine. And now, extensive study is being performed using several gastro-mucoprotective drugs by many researchers. In this review, we introduce the current clinical situation in small intestinal injury of patients under NSAID treatment, and to summarize the molecular mechanism by which NSAID, including acetyl salicylic acid, cause small intestinal damage. In addition, we present results of clinical trials performed so far, and refer the possible preventive method or treatment in the near future.
The aim of this review was to evaluate whether eating vegetables before carbohydrates could reduce the postprandial glucose, insulin, and improve long-term glycemic control in Japanese patients with type 2 diabetes. We studied the effect of eating vegetables before carbohydrates on postprandial plasma glucose, insulin, and glycemic control for 2.5 y in patients with type 2 diabetes. The postprandial glucose and insulin levels decreased significantly when the patients ate vegetables before carbohydrates compared to the reverse regimen, and the improvement of glycemic control was observed for 2.5 y. We also compared the postprandial glucose and glucose fluctuations assessed by continuous glucose monitoring system for 72-h in patients with type 2 diabetes and subjects with normal glucose tolerance when subjects ate vegetables before carbohydrates and carbohydrates before vegetables in a randomized crossover design. The glycemic excursions and incremental glucose peak were significantly lower when the subjects ate vegetables before carbohydrates compared to the reverse regimen. This evidence supports the effectiveness of eating vegetables before carbohydrates on glucose excursions in the short-term and glycemic control in the long-term in patients with type 2 diabetes.
Tumor invasion is the most important factor to decide patient’s prognosis. The relation between reactive oxygen species and tumor invasion is mainly reported that nicotinamide adenine dinucleotide phosphate oxidase in the cell membrane is a reactive oxygen species producer for formulating an invadopodia. On the other hand, mitochondrion was known as one of the most important reactive oxygen species-producer in the cell via an energy transfer system. However, the relation between mitochondrial reactive oxygen species and the tumor invasion was not well clarified. In this study, we evaluated the relation between mitochondrial reactive oxygen species and tumor invasion using a normal gastric mucosal cell-line (RGM-1) and a cancerous mutant RGM-1 cell-line (RGK-1). Manganese superoxide dismutase-expressing RGK-1 cell-lines were used for a scavenging mitochondrial reactive oxygen species. The cells have been evaluated their movement ability as follows; cellular ruffling frequencies, wound healing assay to evaluate horizontal cellular migration, and invasion assay using matrigel to analyze vertical cellular migration. All cellular movement abilities were inhibited by scavenging mitochondrial reactive oxygen species with manganese superoxide dismutase. Therefore mitochondrial reactive oxygen species was one of factors enhancing the tumor invasion in gastric cancer.
Our previous study showed α-lipoic acid (LA) downregulated cell surface β1-integrin expression of v-H-ras-transformed derivative of rat fibroblast with amelioration of their malignant phenotype. Here, we evaluated the ameliorating effect of LA on the malignant characters in H-ras-transformed bladder cancer cells. H-ras mutated bladder cancer line, T24 cells were incubated with LA to evaluate the inhibitory effect on proliferation, migration, invasion and β1-integrin expression. Fluorescence staining of F-actin and western blotting analyses of the related signaling pathways were also performed. LA inhibited the proliferation of T24 cells. Cell adhesion to collagen IV and fibronectin was strikingly inhibited by LA treatment accompanied by downregulation of cell surface but not whole cell β1-integrin expression. LA clearly inhibited cell migration and invasion of T24 cells, which were mimicked by extracellular signal-regulated kinase (ERK) and Akt pathway inhibition. Actually, LA significantly downregulated the phosphorylated ERK and Akt levels. Moreover, LA downregulated phosphorylated focal adhesion kinase level with disappearance of stress fiber formation. Finally, although LA induced the internalization of cell surface β1-integrin, disruption of the raft did not affect the action of LA. Taken together, LA is a promising agent to improve malignant character of bladder cancer cells through regulation of cellular β1-integrin localization.
The mechanism of tumor-specific porphyrin accumulation is not clear. We investigated the expression of proton-coupled folate transporter SLC46A1 in glioma and aimed to clarify the relationship between tumor fluorescence and SLC46A1 expression.We confirmed the expression of SLC46A1 in surgical specimens from 24 glioma patients by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). We also investigated SLC46A1 expression in glioma cell lines by RT-PCR. The cellular uptake of hematoporphyrin derivative in vitro was measured with a microplate reader and fluorescence microscope. In these experiments, we used three human malignant glioma cell lines: U87, U251 and T98G. Immunohistochemistry showed SLC46A1 positivity in the malignant tumor lesion of each specimen. Strong positive SLC46A1 expression was observed in 33% of grade IV, 22% of grade III and 17% of grade II gliomas. All four randomly obtained malignant glioma frozen sections expressed SLC46A1 mRNA by RT-PCR. In vitro, U87 showed the least SLC46A1 expression, U251 was intermediate, and T98G showed the most expression. The amount of hematoporphyrin derivative (HpD) cellular uptake correlated with SLC46A1 expression. These results suggest that the accumulation of HpD in glioma cells is related to SLC46A1 function and SLC46A1 is involved in the mechanism of glioma fluorescence.
To determine the associations between isoflavone (49.72% genistin, 5.32% daidzin, 34.54% glycitin) and breast cancer risk, 150 rats were given 5 mg 7,12-dimethylbenz(a)anthracene and half of them were ovariectomized. Then normal rats and ovariectomized rats were divided into 5 groups: control group, isoflavone high (HI), middle (MI), or low (LI) dose group consuming 100, 500, or 1000 mg isoflavones/kg diet, estrogen group (2.5 mg stilboestrol/kg diet). After 24 weeks, tumor incidences were 73% in control group, 7% in HI, 7% in MI, 27% in LI, and 80% in estrogen group for normal rats; 60% in control group, 13% in HI, 7% in MI, 13% in LI, and 73% in estrogen group for ovariectomized rats. Isoflavone treatment decreased tumor incidence and mean tumor number per rat and increased mean latent period compared with those in control group and estrogen group group significantly (p<0.05). The mRNA and protein expression of estrogen receptor β were significantly higher in isoflavone treatment groups than those in control group group. Moreover, isoflavone treatment significantly decreased 8-hydroxydeoxyguanosine content and increased superoxide dismutase level in normal rats and decreased malondialdehyde concentrations in ovariectomized rats compared with control group. In conclusions, isoflavone intake significantly inhibited the development of premenopausal and postmenopausal mammary tumors.
Nonalcoholic fatty liver disease (NAFLD) can develop into end-stage disease that includes cryptogenic cirrhosis and hepatocellular carcinoma. Bacterial endotoxin, for example lipopolysaccharide (LPS), plays an important role in the pathogenesis of NAFLD. The aim of this study was to assess the role of LPS in the development of NAFLD. Twenty-one male Zucker (fa/fa) rats were divided into three groups: rats fed for twelve weeks on a diet rich in disaccharide (D12 group), rats similarly managed but treated with LPS (LPS group), and those on the same diet for 24 weeks (D24 group). Histological examination demonstrated that this protocol induced hepatic steatosis in the LPS and D24 groups. Significant, marked accumulation of lipid droplets was observed in the LPS group, compared with the D24 group. Rats from the LPS group showed a decrease in plasma adiponectin levels, an increase in plasma leptin levels, and greater expression of FAS and SREBP-1c mRNA in the liver, compared with rats from the D24 group. These finding coincided with histological findings. We therefore suggest that LPS may accelerate the progression of hepatic steatosis.
The aim of the study was to evaluate the anti-obesity effects of two types of meju in diet induced obese C57BL/6J mice. Animals were randomly divided into 4 dietary group (n = 10); normal diet, high fat diet with 30% soybean, high fat diet with 30% traditional meju, high fat diet with 30% standardized meju. After 16 weeks, after animals were sacrificed. It was observed that the high fat diet with 30% traditional meju and high fat diet with 30% standardized meju significantly reduced body weight gain, epididymal fat weight, serum triglyceride along with serum insulin and leptin levels compared to the high fat diet with 30% soybean. And also, the expression levels of hepatic lipid anabolic genes were significantly decreased in the high fat diet with 30% traditional meju and high fat diet with 30% standardized meju compared to the high fat diet with 30% soybean. In conclusion, the assessment of all the obesity markers strongly advocate the anti-obesity effect of traditional as well as standardized meju in diet induce obesity conditions.
Administration of branched-chain amino acids (BCAA) has been reported to improve liver function, quality of life (QOL). However, in some malnourished patients, serum albumin levels do not improve in response to BCAA granules. In this study, we examined the effects of BCAA-enriched enteral nutrition in patients unresponsive to BCAA granules. Thirty-two decompensated cirrhotic patients at Osaka Medical College were enrolled in this study. Since all patients showed no improvement in serum albumin levels despite 3 months of BCAA granule administration, they were administered 50 g of a flavored BCAA-enriched enteral nutrient twice daily, i.e., during the daytime and late evening. Serum albumin levels and major cirrhotic symptoms were examined 1, 3, and 5 months after treatment initiation. Serum albumin levels improved significantly 3 months after treatment initiation (3.14 ± 0.32 g/dl vs 3.5 ± 0.31 g/dl, p<0.01), and Child–Pugh scores decreased significantly (p<0.01). In the majority (53–80%) of patients, muscles cramps, fatigue, fatigability, edema, and sleep disturbance improved within 3 months after therapy initiation. Moreover, approximately 90% of the patients became symptom-free 5 months after treatment initiation. These results indicate that switching to BCAA-enriched nutrients improves QOL of cirrhotic patients unresponsive to BCAA granules.
Using the small intestine enterocyte Caco-2 cell model, sucrase-isomaltase (SI, the mucosal α-glucosidase complex) expression and modification were examined relative to exposure to different mono- and disaccharide glycemic carbohydrates. Caco-2/TC7 cells were grown on porous supports to post-confluence for complete differentiation, and dietary carbohydrate molecules of glucose, sucrose (disaccharide of glucose and fructose), maltose (disaccharide of two glucoses α-1,4 linked), and isomaltose (disaccharide of two glucoses α-1,6 linked) were used to treat the cells. qRT-PCR results showed that all the carbohydrate molecules induced the expression of the SI gene, though maltose (and isomaltose) showed an incremental increase in mRNA levels over time that glucose did not. Western blot analysis of the SI protein revealed that only maltose treatment induced a higher molecular weight band (Mw ~245 kDa), also at higher expression level, suggesting post-translational processing of SI, and more importantly a sensing of maltose. Further work is warranted regarding this putative sensing response as a potential control point for starch digestion and glucose generation in the small intestine.
The purpose of the study was to evaluate the effects of Lactobacillus pentosus strain b240 (b240) intake and appropriate physical training on salivary secretory immunoglobulin A secretion in elderly adults with low physical fitness. Elderly adults with low physical fitness (daily step count below 3,500 steps) were divided into 2 groups: a b240 intake + exercise group (b240 group) and a placebo intake + exercise group (placebo group). Each subject continued intake of b240 or placebo and moderate-intensity resistance exercise for 12 weeks. Before and 4, 8, and 12 weeks after the start of intervention, each subject underwent saliva sampling. Before and after intervention, physical fitness tests and step count were measured. Our results showed that secretory immunoglobulin A secretion in 57 subjects during the b240/placebo intake period was significantly greater in the b240 group than in the placebo group (p<0.05). There were no significant changes in physical fitness tests before and after intervention in the 2 groups. The daily amount of walking increased significantly after intervention in both groups (p<0.05). These results suggest that in elderly adults with low physical activity and fitness, intake of b240 with appropriate physical exercise elevate salivary secretory immunoglobulin A secretion.
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