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Yuji Naito

Publications and source records attributed to Yuji Naito.

At least 19 recordsLinked to original sources
PubMed2026

Crosstalk mediators implicated in the Stevens-Johnson Syndrome through gene regulatory network analysis.

Stevens-Johnson syndrome (SJS) is a rare and severe mucocutaneous disorder often triggered by medications or infections. Our previous research identified that four key genes, Ikzf1, Ptger3, Mavs, and Tlr3 are involved in SJS susceptibility and the conjunctival epithelial innate immune response, demonstrating their role in regulating interferon-stimulated genes. However, the interplay among these regulatory factors remains unclear. This study aimed to elucidate the crosstalk mechanisms between the pathways regulated by these four genes in conjunctival epithelial cells. We constructed a comprehensive gene regulatory network using transcriptomic data from murine conjunctival epithelial cells under 16 distinct conditions, including polyI:C stimulation across wild-type, knockout, and transgenic backgrounds for the key genes. A targeted network analysis systematically identified numerous candidate genes mediating the crosstalk between the regulatory pathways initiated by Ikzf1, Ptger3, Mavs, and Tlr3. The identified candidates suggest the involvement of diverse signaling pathways previously unlinked to SJS pathology. Our findings suggest that the pathogenesis of SJS may arise not from the dysfunction of isolated genes but from the disruption of a balance maintained by intricate pathway crosstalk.

Animals↗
PubMed2006

Short-term high glucose exposure induces monocyte-endothelial cells adhesion and transmigration by increasing VCAM-1 and MCP-1 expression in human aortic endothelial cells.

Acute, short-term hyperglycemia is becoming recognized as an important risk factor for several diseases. In the present study, using human aortic endothelial cells (HAECs), we investigated whether short-term high glucose exposure, either on the scale of hours, could enhance the monocyte adhesion and migration to the subendothelium via increasing expression of adhesion molecules and release of chemotactic factors. HAECs stimulated with 25mM d(+)glucose (HG) for not more than 12h, exhibited rapid up-regulation of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) mRNA and protein. Although intercellular adhesion molecule-1 (ICAM-1) is considered as a marker of the activation of the atherogenic process, early up-regulation was not observed, and VCAM-1 and MCP-1 protein enhance was sufficient to increase the adhesiveness of human monocytes U-937 to HAECs and their transmigration into the subendothelial space after 4h HG stimulation; both effects were prevented by interfering with monoclonal antibodies against VCAM-1, CD11b, and MCP-1. An increased intracellular oxidative stress, a translocation of NF-kappaB to the nucleus and a prevention of adhesion and transmigration of U-937 by interfering with NF-kappaB inhibitors was also observed after a short HG treatment. Taken together, these results suggest that either acute hyperglycemic spikes could exert an influence on the onset of diabetic complications and on the development of the atherogenic profile on diabetic and non-diabetic subjects.

Blood Glucose↗
PubMed2006

CagA protein of Helicobacter pylori: a hijacker of gastric epithelial cell signaling.

Epidemiological study has shown strong correlation between the Helicobacter pylori (H. pylori) infection and gastric carcinogenesis. However, the mechanism by which H. pylori induces gastric carcinogenesis is not known. In this review, we focused on the product of cytotoxin-associated gene A (CagA), one of the important virulence factors of H. pylori. H. pylori injects CagA protein into the host gastric epithelial cells through its needle-like structure, type IV secretion system. Injected CagA hijacks physiological signal transduction and causes pathological cellular response such as increased cell proliferation, motility, apoptosis and morphological change through different mechanisms. H. pylori has been shown to produce reactive oxygen species (ROS) in infected gastric mucosa. Although the main source of ROS production is possibly host neutrophil, we propose novel source of ROS production in this review; CagA itself can induce ROS production in gastric epithelial cell. Excessive ROS production in gastric epithelial cells can cause DNA damage and thus might involve in gastric carcinogenesis. Understanding the molecular mechanism by which H. pylori-induced carcinogenesis is important for developing new strategies against gastric cancer.

Antigens, Bacterial↗
PubMed2006

Role of the thrombin/protease-activated receptor 1 pathway in intestinal ischemia-reperfusion injury in rats.

CXC chemokines, including human interleukin-8 and rat cytokine-induced neutrophil chemoattractant-1, play a crucial role in the pathogenesis of intestinal inflammation induced by ischemia-reperfusion (I-R). Thrombin and its specific receptor, protease-activated receptor 1 (PAR1), act as important players in inflammation. However, the association between thrombin activation and chemokine production during I-R has not been well studied. We investigated whether thrombin and PAR1 might be involved in the pathophysiology of intestinal I-R, using an in vivo model. Intestinal damage was induced by clamping the superior mesenteric artery for 30 min followed by reperfusion in male Wistar rats. Thrombin-antithrombin complex was measured as an indicator of thrombin activation. PAR1 expression in the intestine was evaluated by real-time PCR. The severity of the intestinal mucosal injury was evaluated on the distal segment of the ileum by several biochemical markers and histological findings. Reperfusion significantly increased the serum levels of thrombin-antithrombin complex and enhanced PAR1 expression in the intestinal mucosa. The levels of both intraluminal hemoglobin and protein were significantly increased in the I-R group. The mucosal myeloperoxidase activity and expressions and/or productions of cytokine-induced neutrophil chemoattractant-1 and TNF-alpha were significantly increased after I-R. These increases were inhibited by the treatment of rat with antithrombin intravenously before I-R at a dose of 30 U/kg. These results suggest that the thrombin/PAR1 pathway plays an important role in the production of these cytokines during I-R and that antithrombin exerts potent anti-inflammatory effects on this injury via inhibition of proinflammatory cytokines.

Animals↗
PubMed2006

A novel potent inhibitor of inducible nitric oxide synthase, ONO-1714, reduces hyperoxic lung injury in mice.

STUDY OBJECTIVES: High-concentration oxygen therapy is used to treat tissue hypoxia, but hyperoxia causes lung injury. Overproduction of nitric oxide by nitric oxide synthase (NOS) is thought to promote hyperoxic lung injury. The present study was conducted to examine the role of inducible nitric oxide synthase (iNOS) in hyperoxic lung injury in mice. MEASUREMENTS AND RESULTS: Mice were exposed to >98% oxygen for 72 h, and ONO-1714 (0.05 mg/kg) (ONO) was subcutaneously administered to block iNOS. Hyperoxia significantly increased total cell count, protein concentration, and nitrites/nitrates in the bronchoalveolar lavage fluid and proinflammatory cytokines in the lung tissue. ONO significantly prevented the increases in all of these variables. ONO suppressed histologic evidence of lung injury. ONO markedly inhibited iNOS protein expression and nitrotyrosine production in lung homogenates. After exposure to hyperoxia, alveolar epithelial cells stained positively for 8-hydroxy-2'-deoxyguanosine, a proper marker of oxidative DNA damage by reactive oxygen species. ONO attenuated this finding. CONCLUSIONS: NOS play important roles in the pathogenesis of hyperoxic lung injury. Selective iNOS inhibitors may be useful for the treatment of hyperoxic lung injury.

Amidines↗
PubMed2006

Methylparaben potentiates UV-induced damage of skin keratinocytes.

For many years, methylparaben (MP) has been used as a preservative in cosmetics. In this study, we investigated the effects of ultraviolet-B (UVB) exposure on MP-treated human skin keratinocytes. HaCaT keratinocyte was cultured in MP-containing medium for 24h, exposed to UVB (15 or 30 mJ/cm(2)) and further cultured for another 24h. Subsequent cellular viability was quantified by MTT-based assay and cell death was qualified by fluorescent microscopy and flow cytometry. Oxidative stress, nitric oxide (NO) production and cellular lipid peroxidation were measured using fluorescent probes. In addition, activation of nuclear factor kappa B and activator protein-1 was assessed by electro-mobility gel-shift assay. Practical concentrations of MP (0.003%) had a little or no effect on cellular viability, oxidative stress, NO production, lipid peroxidation and activation of nuclear transcription factors in HaCaT keratinocytes. Low-dose UVB also had little or no effect on these parameters in HaCaT keratinocytes. However, UVB exposure significantly increased cell death, oxidative stress, NO production, lipid peroxidation and activation of transcription factors in MP-treated HaCaT keratinocytes. These results indicate that MP, which has been considered a safe preservative in cosmetics, may have harmful effects on human skin when exposed to sunlight.

Apoptosis↗
PubMed2006

Azelnidipine, a new calcium channel blocker, inhibits endothelial inflammatory response by reducing intracellular levels of reactive oxygen species.

Oxidized low-density lipoprotein (ox-LDL) plays an important in the development of atherosclerosis by stimulating the production of reactive oxygen species in endothelial cells, and thereby up-regulating vascular cell adhesion molecule-1 (VCAM-1). The objectives of the present study were to determine the effects of azelnidipine, a new calcium channel blocker, on the expression of VCAM-1 induced by 7-ketocholesterol, components of ox-LDL, and tumor necrosis factor-alpha (TNF-alpha). The scavenging activities of azelnidipine against superoxide, hydroxyl, and carbon-centered radicals were determined by electron spin resonance assay. The levels of intracellular reactive oxygen species were determined fluorometrically with the use of dichlorodihydrofluorescein diacetate (H(2)DCF-DA). Human aortic endothelial cells and U937 were used as endothelial cells and monocytic cells, respectively. The surface expression and mRNA levels of VCAM-1 were determined by enzyme immunoassay and RT-PCR performed on endothelial cell monolayers stimulated with 7-ketocholesterol or TNF-alpha. The numbers of monocytic cells adhering on the stimulated endothelial cells were counted in the microscopic fields. Translocation of p65 protein to the nucleus was estimated by fluorescence microscopy. Azelnidipine, but not nifedipine, reduced the signal intensity of 1,1-diphenyl-2-picrylhydrazyl radicals. Azelnidipine scavenged hydroxyl radicals, but not superoxide radicals. Intracellular levels of reactive oxygen species and RelA (p65) nuclear translocation in stimulated endothelial cells were reduced by azelnidipine. Azelnidipine significantly inhibited the expression of protein and mRNA of VCAM-1, and prevented the U937 cell adhesion to endothelial cells treated with 7-ketocholesterol or TNF-alpha. These results suggest that azelnidipine works as an anti-atherogenic agent by inhibiting the reactive oxygen species-dependent expression of VCAM-1 induced by 7-ketocholesterol and TNF-alpha.

Aorta↗
PubMed2006

Gene expression profiles on hypoxia and reoxygenation in rat gastric epithelial cells: a high-density DNA microarray analysis.

Previous investigations have demonstrated that the cellular signaling induced by hypoxia-reoxygenation is a major pathway contributing to gastric mucosal injury induced by stress, non-steroidal anti-inflammatory drugs, and Helicobacter pylori. The aim of the present study was to perform a gene expression analysis of the gastric mucosal cellular response and to define the protective molecules in hypoxia and reoxygenation using a high-density DNA microarray analysis. Normal rat gastric mucosal (RGM-1) cells were subjected to hypoxia for 2 h, and reoxygenation was initiated by placing the cells in an environment of normoxia for 2, 4, or 8 h. Total RNA was extracted, and differences in the gene expression profiles between the normoxia and hypoxia groups or among the different durations of reoxygenation were investigated using a high-density DNA microarray. HIF-1- and apoptosis-related genes were modulated by hypoxia. Moreover, inflammation-, stress-, and wound- healing-related genes were regulated by reoxygenation following hypoxia. In particular, the expression of heat shock protein-70, amphiregulin and cyclooxygenase-2 were upregulated during reoxygenation following hypoxia, suggesting that these upregulations may play an important role in maintaining cell survival and supporting cell function.

Animals↗
PubMed2006

Inhibitory effect of fermented milk on delayed-onset muscle damage after exercise.

Milk fermented with a starter containing Lactobacillus helveticus and Saccharomyces cerevisiae is drunk on a daily basis by many people in Japan and has several beneficial effects. We studied the influence of this fermented milk product on muscle damage after prolonged exercise in rats. Wistar rats were divided into four groups: rested controls, rested rats given fermented milk diet, exercised rats and exercised rats given fermented milk diet. After 3 weeks of acclimatization, both exercise groups were made to run on a treadmill at 26 m/min for 60 min. Exercise increased the serum creatine kinase level, as well as myeloperoxidase activity and the level of thiobarbituric-acid-reactive substances in the gastrocnemius muscle after 24 h. These changes were ameliorated by intake of fermented milk. An increase of CINC-1 was also ameliorated by fermented milk. Furthermore, milk diet increased the mRNA and protein levels of protective proteins such as antioxidants and chaperone proteins. These results indicate that fermented milk can ameliorate delayed-onset muscle damage after prolonged exercise, which is associated with an increased antioxidant capacity of muscles.

Animals↗
PubMed2006

Exercise and functional foods.

Appropriate nutrition is an essential prerequisite for effective improvement of athletic performance, conditioning, recovery from fatigue after exercise, and avoidance of injury. Nutritional supplements containing carbohydrates, proteins, vitamins, and minerals have been widely used in various sporting fields to provide a boost to the recommended daily allowance. In addition, several natural food components have been found to show physiological effects, and some of them are considered to be useful for promoting exercise performance or for prevention of injury. However, these foods should only be used when there is clear scientific evidence and with understanding of the physiological changes caused by exercise. This article describes various "functional foods" that have been reported to be effective for improving exercise performance or health promotion, along with the relevant physiological changes that occur during exercise.

Athletic Injuries↗
PubMed2006

Rosuvastatin reduces rat intestinal ischemia-reperfusion injury associated with the preservation of endothelial nitric oxide synthase protein.

AIM: To investigate the protective effect of rosuvastatin on ischemia-reperfusion (I-R)-induced small intestinal injury and inflammation in rats, and to determine the effect of this agent on the expression of endothelial nitric oxide synthase (eNOS) protein. METHODS: Intestinal damage was induced in male Sprague-Dawley rats by clamping both the superior mesenteric artery and the celiac trunk for 30 min, followed by reperfusion for 60 min. Rosuvastatin dissolved in physiological saline was administered intraperitoneally 60 min before ischemia. The severity of the intestinal mucosal injury and inflammation were evaluated by several biochemical markers, as well as by histological findings. The protein levels of eNOS were determined by Western blot. RESULTS: The levels of both intraluminal hemoglobin and protein, as indices of mucosal damage, were significantly increased in the I-R group compared with those in the sham-operated group. These increases, however, were significantly inhibited by treatment with rosuvastatin in a dose-dependent manner. The protective effects of rosuvastatin were also confirmed by histological findings. Exposure of the small intestine to I-R resulted in mucosal inflammation characterized by significant increases in thiobarbituric acid-reactive substances, tissue-associated myeloperoxidase activity, and the mucosal contents of rat cytokine-induced neutrophil chemoattractant-1 (CINC-1) and tumor necrosis factor-alpha (TNF-alpha). These increases in inflammatory parameters after I-R were significantly inhibited by pretreatment with rosuvastatin at a dose of 10 mg/kg. Furthermore, mRNA expression of CINC-1 and TNF-alpha was increased after I-R, and this increase was also inhibited by rosuvastatin. The mucosal protein levels of eNOS decreased during I-R, but were preserved in rats treated with rosuvastatin. CONCLUSION: Rosuvastatin inhibits rat intestinal injury and inflammation induced by I-R, and its protection is associated with the preservation of eNOS protein.

Animals↗
PubMed2006

CV-11974, angiotensin II type I receptor antagonist, protects against ischemia-reperfusion injury of the small intestine in rats.

BACKGROUND: Angiotensin II has been implicated in the pathogenesis of vascular inflammation in various organs. The aim of the present study was to examine the effect of angiotensin II type I receptor antagonist, CV-11974, on reperfusion-induced small intestinal injury in rats. METHODS: Intestinal damage was induced by clamping both the superior mesenteric artery and the celiac trunk for 30 min followed by reperfusion for 60 min in male Wistar rats. CV-11974 was given to the rats by intravenous injection 1 h before the vascular clamping. The intestinal mucosal injury and inflammation were evaluated by biochemical markers and histological findings. Thiobarbituric acid reactive substances and tissue-associated myeloperoxidase (MPO) activity were measured in the gastric mucosa as indices of lipid peroxidation and neutrophil infiltration. The expressions of pro-inflammatory cytokines (CINC-1) in intestinal mucosa were measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-PCR (RT-PCR). In additional experiments with an in vitro flow system, human neutrophils were perfused on human umbilical vein endothelial cells (HUVEC) pretreated with anoxia-reoxygenation with or without CV-11974 and then the adhesive neutrophils were counted. RESULTS: Reperfusion after ischemia resulted in an increase in luminal protein concentrations, hemoglobin concentrations, thiobarbituric acid reactive substances, and MPO activity. Pretreatment with CV-11974 significantly inhibited the increases in these parameters. CV-11974 also inhibited increases in intestinal CINC-1 protein and mRNA expression induced by ischemia-reperfusion. Moreover, in an in vitro study, CV-11974 significantly inhibited the adherence of neutrophils to HUVEC exposed to reoxygenation after anoxia. CONCLUSIONS: These results suggest that the blockade of angiotensin II type I receptor by treatment with CV-11974 remarkably reduced the reperfusion-induced intestinal injury.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Role of pancreatic trypsin in chronic esophagitis induced by gastroduodenal reflux in rats.

BACKGROUND: Reflux of the duodenal contents with gastric acid has been reported to contribute to the development of esophageal mucosal damage and inflammation. Recent studies show that pancreatic trypsin can stimulate the production of inflammatory mediators, including chemokines and prostaglandins from human esophageal epithelial cells in vitro. The aim of the present study was to investigate the role of pancreatic trypsin in the pathogenesis of chronic esophageal inflammation induced by gastroduodenal reflux in rats. METHODS: Esophagogastroduodenal anastomosis was carried out in male Wistar rats by anastomosing the jejunum to the gastroesophageal junction under diethyl ether inhalation anesthesia. The animals undergoing surgery were treated with the control diet, rabeprazole sodium, nizatidine, ecabet sodium, camostat mesilate (CMM), ONO-1714, a specific inducible nitric oxide synthase (iNOS) inhibitor, or meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor. Esophageal injury was evaluated by macroscopic and microscopic findings, and mRNA expression for CINC-1, COX-2, and iNOS was determined by real-time polymerase chain reaction (PCR). Trypsin activity within the esophageal lumen was measured 2 weeks after surgery, and the expression of protease-activated receptor (PAR)-1 and -2 was confirmed by reverse transcription (RT)-PCR. RESULTS: At 8 weeks after surgery, gastroduodenal reflux induced esophageal erosions and ulcer formation as well as marked thickening of the esophageal wall. Histological study showed an increase of thickness of the esophageal mucosa, hyperplasia of the epidermis and basal cells, ulcer formation, and marked infiltration of inflammatory cells. The macroscopic ulcer score and histological ulcer length were significantly reduced by treatment with rabeprazole or CMM but not by nizatidine or ecabet sodium, compared with each control. Rabeprazole, nizatidine, or ecabet sodium did not affect the severity of mucosal hyperplastic scores or histological parameters in esophagitis. In contrast, the CMM group showed a significant decrease in the mucosal hyperplastic and inflammatory scores. The enhanced expression of CINC-1, COX-2, and iNOS mRNA in the control group was also markedly inhibited in the CMM-treated group. ONO-1714 or meloxicam treatment significantly reduced the macroscopic scores of ulcer and hyperplasia. The trypsin activity in the esophageal lumen was significantly increased in the control diet group, and this increase was significantly inhibited in the CMM-treated group. The expression of PAR-1 and -2 mRNA was confirmed in rat esophageal epithelium. CONCLUSIONS: With this model, we have demonstrated that CMM significantly reduces inflammation and hyperplasia in the esophageal mucosa. These results indicate that trypsin, which is primarily inhibited by CMM, plays an important role in the mucosal damage induced by gastroduodenal reflux and that it can be a therapeutic target in patients with gastroduodenal reflux esophagitis.

Animals↗
PubMed2006

Surgical repair of the common arterial trunk in a neonate with a downsized valve allograft.

In the present report we describe a neonate with the common arterial trunk who underwent reconstruction of the right ventricular outflow tract with a downsized value allograft. Our experience and results suggest that reducing the size of the allograft is a promising surgical option for young infants in whom reconstruction of the nonregurgitant pulmonary circulatory system is absolutely needed for a smooth postoperative recovery.

Child, Preschool↗
PubMed2006

Anti-tryptase treatment using nafamostat mesilate has a therapeutic effect on experimental colitis.

OBJECTIVE: Mast cell tryptase has been proposed to be involved in the pathogenesis of human inflammatory bowel disease (IBD). Recently, it was reported that a low dose of nafamostat mesilate (NM), a serine protease inhibitor that is widely used to treat disseminated intravascular coagulation (DIC) and acute pancreatitis, can selectively inhibit human tryptase activity. The aim of this study was to investigate the anti-inflammatory effects of NM on experimental colitis in rats. MATERIAL AND METHODS: Colitis was induced in male Wistar rats using an enema of trinitrobenzene sulfonic acid (TNBS) dissolved in 50% ethanol. NM or 5-aminosalicylic acid (5-ASA), foundation therapy for mild-to-moderate IBD, was administered via the anus once a day on each of the 6 days after administration of TNBS. Colonic inflammation was assessed 1 week after TNBS administration. RESULTS: Intracolonic administration of TNBS resulted in the infiltration of numerous tryptase-positive cells in the colonic mucosa. The colonic mucosal injury induced by TNBS was significantly decreased by treatment with NM or 5-ASA. The increases in thiobarbituric acid-reactive substances (TBA-RS), myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-alpha and cytokine-induced neutrophil chemoattractants-1 (CINC-1) in the colonic mucosa were inhibited in the NM group and the 5-ASA group, without significant differences between them. CONCLUSIONS: These results indicate that a low dose of NM can inhibit the colonic mucosal inflammation induced by TNBS in rats, which suggests that anti-tryptase therapy using low doses of NM has excellent potential to become a new therapeutic strategy for IBD.

Aminosalicylic Acids↗
PubMed2006

Oxidative stress involvement and gene expression in indomethacin-induced gastropathy.

It has been proposed that neutrophil- and oxygen radical-dependent microvascular injuries are important prime events that lead to gastric mucosal injury induced by indomethacin. Reactive oxygen species (ROS) produced by activated neutrophils after indomethacin treatment cause gastric mucosal injury via ROS-mediated oxidation of important biomolecules such as lipid, protein, and DNA. In addition, it has been revealed that indomethacin-induced gastric mucosal injury occurs via gastric epithelial cell apoptosis. However, there is little known about the mechanism of indomethacin-triggered cellular response and apoptotic signaling in gastric mucosal cells. In the present study, we summarize the evidence that supports the involvement of oxidative stress and apoptosis in indomethacin-induced gastropathy, and review the gene expression profiles of gastric epithelial cells after indomethacin treatment determined by DNA microarray analysis.

Alanine↗
PubMed2006

Contrasting genome-wide distribution of 8-hydroxyguanine and acrolein-modified adenine during oxidative stress-induced renal carcinogenesis.

Oxidative stress is a persistent threat to the genome and is associated with major causes of human mortality, including cancer, atherosclerosis, and aging. Here we established a method to generate libraries of genomic DNA fragments containing oxidatively modified bases by using specific monoclonal antibodies to immunoprecipitate enzyme-digested genome DNA. We applied this technique to two different base modifications, 8-hydroxyguanine and 1,N6-propanoadenine (acrotein-Ade), in a ferric nitrilotriacetate-induced murine renal carcinogenesis model. Renal cortical genomic DNA derived from 10- to 12-week-old male C57BL/6 mice, of untreated control or 6 hours after intraperitoneal injection of 3 mg iron/kg ferric nitrilotriacetate, was enzyme digested, immunoprecipitated, cloned, and mapped to each chromosome. The results revealed that distribution of the two modified bases was not random but differed in terms of chromosomes, gene size, and expression, which could be partially explained by chromosomal territory. In the wild-type mice, low GC content areas were more likely to harbor the two modified bases. Knockout of OGG1, a repair enzyme for genomic 8-hydroxyguanine, increased the amounts of acrolein-Ade as determined by quantitative polymerase chain reaction analyses. This versatile technique would introduce a novel research area as a high-throughput screening method for critical genomic loci under oxidative stress.

Acrolein↗