THE VIBRATIONAL RAMAN SPECTRA AND PHOTON—INDUCED OXIDATION PHENOMENA OF PURIFIED SOLID FILMS OF C_(60)

The vibrational Raman spectra have been obtained for purified solid films C_(60). Three bands were observed out of the total of 10 that were theoretically predicted. Some phenomena which may be due to photon-induced oxidation in the vibrational Raman measuring were observed.

Self-lubrication of tribologically-induced oxidation during dry reciprocating sliding of aged Ti–Ni51.5 at% alloy

The tribological behaviors of Ti–Ni51.5 at%alloy strengthened by finely dispersed Ni_(4)Ti_(3) particles in reciprocating sliding against GCr15,Al_(2)O_(3),and ZrO_(2) at room temperature were studied.Interestingly,the coefficient of friction(COF)suffered a sheer drop(from 0.9 to 0.2)when the aged alloy slid against GCr15 at a frequency of 20 Hz under a 20 N load without lubrication.However,severe‐mild wear transition disappeared when a solutionized alloy was used.Moreover,the COF stabilized at a relatively high level when Al_(2)O_(3) and ZrO_(2) were used as counterparts,although their wear mechanisms showed signs of oxidation.Scanning electron microscopy(SEM)and X‐ray element mappings of the wear scars of the counterparts clearly indicate that the formation of well‐distributed tribo‐layer and material transfer between the ball and disk are pivotal to the severe‐to‐mild wear transition in the aged Ti–Ni51.5 at%alloy/GCr15 friction pair.The higher microhardness and superelasticity of the aged alloy significantly accelerate the material transfer from GCr15 to the disk,forming a glazed protective tribo‐layer containing Fe‐rich oxides.

Expression and activity of inducible nitric oxide synthase and endothelial nitric oxide synthase correlate with ethanolinduced liver injury

AIM： To study the expression and activity of inducible nitric oxide synthase （iNOS） and endothelial nitric oxide synthase （eNOS） in rats with ethanol-induced liver injury and their relation with liver damage, activation of nuclear factor-KB （NF-κB） and tumor necrosis factor-α （TNF-α） expression in the liver. METHODS： Female Sprague-Dawley rats were given fish oil （0.5 mL） along with ethanol or isocaloric dextrose daily via gastrogavage for 4 or 6 wk. Liver injury was assessed using serum alanine aminotransferase （ALT） activity and pathological analysis. Liver malondialdehyde （MDA）, nitric oxide contents, iNOS and eNOS activity were determined. NF-κB p65, iNOS, eNOS and TNF-α protein or mRNA expression in the liver were detected by immunohistochemistry or reverse transcriptase-polymerase chain reaction （RT-PCR）. RESULTS： Chronic ethanol gavage for 4 wk caused steatosis, inflammation and necrosis in the liver, and elevated serum ALT activity. Prolonged ethanol administration （6 wk） enhanced the liver damage. These responses were accompanied with increased lipid peroxidation, NO contents, iNOS activity and reduced eNOS activity. NF-κB p65, iNOS and TNF-α protein or mRNA expression were markedly induced after chronic ethanol gavage, whereas eNOS mRNA expression remained unchanged. The enhanced iNOS activity and expression were positively correlated with the liver damage, especially the necro-inflammation, activation of NF-KB, and TNF-α mRNA expression. CONCLUSION： iNOS expression and activity are induced in the liver after chronic ethanol exposure in rats, which are correlated with the liver damage, especially the necro-inflammation, activation of NF-KB and TNF-α expression, eNOS activity is reduced, but its mRNA expression is not affected.

Homocysteine-induced Enhanced Expression of Tissue Factor in Human Vascular Smooth Muscle Cells

The homocysteine （Hcy）-induced tissue factor （TF） expression in human vascular smooth muscle cells （VSMCs） and the effect of Hcy on the activity of nuclear factor-kappaB （NF-кB） and the expression of inducible nitric oxide synthase （iNOS） were investigated. Human umbilical artery VSMCs were cultured by tissue explanting method, identified by α-actin immunohistochemistry, and incubated with different concentrations of Hcy/PTDC （NF-кB inhibitor）. Semi-quantitative RT-PCR was performed to detect the expression of TF mRNA in VSMCs. Flow cytometry was used to assay the expression of TF protein on the surface of VSMCs and the expression of iNOS in VSMCs. Western blot was carried out to detect the expression of NF-кB protein in nuclei. The results showed that Hcy could induce VSMCs expressing TF mRNA significantly after the VSMCs were incubated with Hcy at concentrations of 10, 100, 500 μmol/L respectively. There was low expression level of TF protein on the surface of the resting VSMCs and Hcy could also induce VSMCs expressing TF pro- tein on the cell surface in different concentrations. Additionally, Hcy could rapidly induce the activation of NF-кB and this effect could be significantly inhibited by PDTC. Hcy alone could not induce the expression of iNOS in VSMCs. It was concluded that Hcy could significantly induce the expression of TF in VSMCs and enhance the activation of NF-ΚB, subsequently mediate TF gene expression and protein synthesis. NF-кB-mediated expression of TF in VSMCs might be the important mechanism of atherosclerosis and thrombosis induced by Hcy.

Tea polyphenols inhibit expressions of iNOS and TNF-a and prevent lipopolysaccharide-induced liver injury in rats

BACKGROUND: Tea polyphenols have been shown to protect against carbon tetrachloride ( CCl4) -induced liver injury, liver fibrosis, hepatic ischemia-reperfusion injury. In this study, we examined the effect of tea polyphenols on lipopolysaccharide ( LPS ) -induced liver injury, and explored its mechanisms. METHODS: Sprague-Dawley rats received tea polyphenols (100 mg · kg-1·d-1) or vehicle (water) intragastrically by gavage for 14 days, followed by LPS (5 mg/kg) or saline injection intraperitoneally. Liver injury was assessed by biochemical assay and pathological analysis. Serum tumor necrosis factor-α (TNF-α) levels and liver malondialdehyde (MOA) contents were determined. Inducible nitric oxide synthase (iNOS) protein and TNF-α, iNOS and en-dothelial nitric oxide synthase (eNOS) mRNA expressions in the liver were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. RESULTS: Administration of LPS resulted in liver injury in rats, evidenced by elevated activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatocellular necrosis, and neutrophil infiltration in the liver. These responses were associated with increased serum TNF-α levels, induced iNOS protein, expressions of TNF-α, iNOS mRNA in the liver and elevated lipid peroxidation at 90 minutes or 6 hours after LPS injection. Pretreatment with tea polyphenols attenuated LPS-induced liver injury, and blunted the rises of serum TNF-α levels and lipid peroxidation and the induction of expressions of TNF-α, iNOS in the liver. CONCLUSION: Tea polyphenols prevent LPS-induced liver injury, and the mechanisms may involve the reduction of serum TNF-α levels and lipid peroxidation and the suppression of TNF-α, iNOS expressions in the liver.

Puerarin antagonizes peroxyntrite-induced injury in retinal pigment epithelial cells

A rat model of diabetes mellitus was established by intraperitoneal injection of streptozotocin. Three days later, the rats were intraperitoneally administered 140 mg puerarin/kg daily, for a total of 60 successive days. DNA ladder results showed increased apoptosis over time in retinal pigment epithelial cells from rats with streptozotocin-induced diabetes mellitus. Western blot analysis, Reverse transcription-PCR, immunohistochemistry, and flow cytometry results showed increased expression of 3-nitrotyrosine, a peroxyntrite marker, as well as inducible nitric synthase and Fas/FasL, in retinal pigment epithelial cells. Puerarin reversed these changes, and results demonstrated that puerarin inhibited Fas/FasL expression and alleviated peroxyntrite injury to retinal pigment epithelial cells. These results suggested that puerarin inhibited production of inducible nitric oxide synthase and directly antagonized peroxyntrite injury in retinal pigment epithelial cells.

Lanthanum Chloride Inhibiting Expression of Inducible Nitric Oxide Synthase in RAW264.7 Macrophages Induced by Lipopolysaccharide

Nitric oxide（NO）and its reaction products were key players in the pathophysiology of sepsis and shock.The present study was designed to explore the effects of lanthanum chloride（LaCl3）on inducible nitric oxide synthase（iNOS）expression,at both gene and protein levels,in RAW264.7 macrophages induced by Lipopolysaccharide（LPS）.Reverse transcription polymerase chain reaction（RT-PCR）,immunofluorescence,and western blot were employed to measure iNOS gene expression,localization,and protein expression respectively.NO production in culture supernatants was detected by the nitrate reductase method.The results showed that LaCl3 significantly attenuated the iNOS gene and protein expression,as well as NO production in RAW264.7cells induced by LPS.

Attenuation of cisplatin induced ototoxicity by sound preonditioning through NO pathway

Objective：To explore the protective effect of sound preconditioning against ototoxicity induced by cisplatin and its possible mechanism with respect to the nitric oxide （NO） pathway. Methods： Albino guinea pigs were divided into silent control, CDDP,sound preconditioning and sound preconditioning＋CDDP groups. The animals of the CDDP group were injected with cisplatin intravenously 8 mg/kg b.w. The animals in the sound preconditioning were exposed to white noise at 85dB SPL, 5h/d, for 10 d （sound preconditioning）. The animals in the sound preconditioning＋CDDP group were treated with sound preconditioning first and then administrated with cisplatin intravenously 8 mg/kg b.w. Hearing thresholds of auditory brainstem responses （ABRs） of all animals were measured to evaluate hearing function. Hair cell loss was estimated via surface preparation. Cochlear tissue was assayed for measurement of NO level and immunohistochemistry method was used for inducible nitric oxide synthase （iNOS） analysis. Results： There was no significant difference between the silent control and sound preconditioning animals with respect to either functional or histological measures. Among the animals in the CDDP group, there was a significant elevation of threshold at the high test frequencies after administration compared with the silent control group （P〈0. 05）. Morphological examination showed that there was obvious loss of the OHC, especially in the third row of the basal turn. The NO level and immunoreactivity to iNOS in this group were higher and more intensive than those of the silent control group （P〈0. 05）. The ABR thresholds in the sound preconditioning ＋ CDDP group were much lower than those of the CDDP group （P〈0.05）. Slight sporadic loss of OHC was found in this group. The immunoreactivity to iNOS and the level of NO in cochlea decreased significantly compared with the CDDP group （P〈 0. 05）. Conclusion： It is suggested that sound preconditioning, to some extent, provides protective effect against ototoxicity of cisplatin. The excess synthesis of NO induced by the over-expressed of iNOS may be involved in the CDDP induced ototoxicity. The possible mechanism is related to suppression of the NO pathway.

Role of p38 MAPK in lipopolysaccharide-induced iNOS expression by endothelial cells

Objective:To examine the role of p38 mitogen-activated protein kinase (MAPK) in NO production and Inos expression in human endothelial cells stimulated by lipopolysaccharide (LPS). Methods: The NO level in the supernatant of the cell culture media was measured with Griess method, expressions of Inos protein and Mrna in vitro cultured endothelial cell line ECV304 were detected with immunofluorescence analysis and reverse transcriptase-PCR respectively. Immunokinase assay was employed to measure P38mapk activity. Results: Compared with the basal level of Inos expression and NO production, the NO level and the expressions of Inos Mrna and protein in the cells were increased after LPS stimulation. P38mapk activity in ECV304 cells exhibited a marked increase at 15 min after LPS stimulation, lasting for about 45 min before gradually decline. The Inos protein and Mrna expressions induced by LPS stimulation was significantly inhibited by SB203580 [4-(4-fluorophenyl)-2-(4- methylsulfinylphenyl)-5-(4-pyridyl) imidazole], a highly specific inhibitor of p38 MAPK. Conclusion: p38 MAPK plays an important role in iNOS expression and NO production in ECV304 cells, and the inhibition of the signal transduction pathway can be effective to reduce the production of iNOS and other cytokines, and therefore constitutes a useful strategy for treating septic shock or inflammation.

Expression of Endothelial Nitric Oxide Synthase Traffic Inducer in the Placenta of Pregnancy Induced Hypertension

The expression of endothelial nitric oxide synthase traffic inducer （NOSTRIN） in the placenta of the patients with pregnancy induced hypertension （PIH） was detected and its role in the pathogenesis of PIH was studied. The pathological changes in placental vessels were observed by HE staining. NO2-/NO3- , the stable metabolic end products of NO, was measured with nitrate reductase. The eNOS activity in placental tissues was assayed by spectrophotometry. Western blot analysis was applied to detect NOSTRIN expression. The incidence of thickening and fibronoid necrosis of placental vessels was significantly higher in women with PIH than in the normal group （P〈 0.01）. The levels of placental NO2-/NO3- in PIH patients （27. 53±7.48 μmol/mg） were significantly lower than in normal group （54. 27±9.53 μmol/mg, P〈0.01）. The activity of eNOS was significantly decreased in PIH group （12. 826±3.61 U/mg） as compared with that in normal group （21. 72±3.83 U/mg, P〈0.01）. Western blot analysis revealed that both groups expressed 58 kD NOSTRIN, but the protein level was significantly higher in women with PIH than in the normal group （P〈0.01）. A significant negative correlation existed between the expression of NOSTRIN protein and the activity of eNOS in placental tissue of women with PIH （r=-0.57, P〈0.01）. It was concluded that the level of NOSTRIN expression in placenta of women with PIH was increased, which may play an important role in the pathogenesis of PIH.

Changes in Human Umbilical Vein Endothelial Cells Induced by Endothelial Nitric Oxide Synthase Traffic Inducer

This study investigated the changes in human umbilical vein endothelial cells （HUVECs） induced by overexpression of endothelial nitric oxide synthase traffic inducer （NOSTRIN） and its role in cellular injury. Recombinant NOSTRIN-expressing and empty vectors were transfected into cultured HUVECs, and factor Ⅷ-related antigen was examined by using immunohistochemical analysis. Growth curves were generated for both transfected and untransfected cells and these indicated that the prolifera- tive ability of cells overexpressing NOSTRIN was significantly decreased. The expression of NOSTRIN and eNOS proteins was detected by using Western blot analysis, endothelial NOS （eNOS） activity was assayed by using spectrophotometry, and NO2-/NO3- levels were measured usin~ nitrate reductase. Immunohistochemical analysis demonstrated that all groups expressed NOSTRIN in the plasma mem- brane and cytoplasm, and Western blot analysis confirmed that NOSTR1N levels were significantly higher in cells transfected with the NOSTR1N plasmid （P〈0.01）. The activity of eNOS and the levels of NO2-/NO3 were significantly decreased in NOSTRIN overexpressing cells as compared with empty vector and untransfected cells （P〈0.01 and P〈0.01, respectively）. Morphological and ultrastructural changes were observed under light and electron microscopy, and it was found that NOS- TRIN-overexpressing cells were elongated with deformities of the karyotheca, injury to the plasma membrane, increased lipids in the cytoplasm, and shortened microvilli. This study showed that overex- pression of NOSTRIN had a significant effect on eNOS activity in HUVECs and resulted in significant cellular damage.

Expressions of inducible nitric oxide synthase and matrix metalloproteinase-9 and their effects on angiogenesis and progression of hepatocellular carcinoma

AIM： To determine the expressions of inducible nitric oxide synthase （iNOS） and matrix metalloproteinase-9 （MMP-9） in hepatocellular carcinoma （HCC） and to investigate the relationship between iNOS and MMP-9 expression and their effects on angiogenesis and progression of HCC.METHODS： In this study, we examined iNOS, MMP-9, and CD34 expression in specimens surgically removed from 32 HCC patients and 7 normal liver tissues by immunohistochemical staining. Meanwhile, microvessel density （MVD） was determined as a marker of angiogenesis by counting CD34-positive cells. RESULTS： The positive rates of iNOS and MMP-9 expression were 71.88% （23/32） and 78.13% （25/32） in HCC. MMP-9 expression was significantly correlated with tumor size, capsule status, TNM stage, and risk of HCC recurrence （P = 0.032, P= 0.033, P= 0.007, and P= 0.001, respectively）. There was also a significant relationship between iNOS expression and capsule status and risk of HCC recurrence （P = 0.049 and P = 0.004, respectively）, but no correlation between iNOS expression and tumor size and TNM stage. There was a positive association between MVD and TNM stage and risk of HCC recurrence （P = 0.037 and P = 0.000, respectively）. The count of MVD was significantly different in different iNOS and MMP-9 immunoreactivity groups （F= 17.713 and 17.097, P= 0.000 and P = 0.000, respectively）. The examination of Spearman＇s rank correlation coefficient showed that there was a significant positive correlation between MVD and iNOS, MMP-9 immunoreactivity （r = 0.754 and 0.751, P= 0.000 and P=-0.000, respectively）. There was also a significant association between MMP-9 and iNOS expression in HCC （P = 0.010）. CONCLUSION： Nitric oxide （NO） produced by iNOS could modulate MMP-9 production and therefore contribute totumor cell angiogenesis and invasion and metastasis in HCC. The strong expression of iNOS and MMP-9 in HCC may be helpful in evaluating the recurrence of HCC, predicting poor prognosis. For patients with strong expression of MMP-9 and iNOS, the optimal treatment scheme needs to be selected.

Role of neuronal nitric oxide synthase and inducible nitric oxide synthase in intestinal injury in neonatal rats

AIM： TO investigate the dynamic change and role of neuronal nitric oxide synthase （nNOS） and inducible nitric oxide synthase （iNOS） in neonatal rat with intestinal injury and to define whether necrotizing enterocolitis （NEC） is associated with the levels of nitric oxide synthase （NOS） in the mucosa of the affected intestine tissue. METHODS： Wistar rats less than 24 h in age received an intraperitoneal injection with 5 mg/kg lipopolysaccharide （LPS）. Ileum tissues were collected at 1, 3, 6, 12 and 24 h following LPS challenge for histological evaluation of NEC and for measurements of nNOS and iNOS. The correlation between the degree of intestinal injury and levels of NOS was determined. RESULTS： The LPS-injected increase in injury scores pups showed a significant versus the control. The expression of nNOS protein and mRNA was diminished after LPS injection. There was a negative significant correlation between the nNOS protein and the grade of median intestinal injury within 24 h. The expression of iNOS protein and mRNA was significantly increased in the peak of intestinal injury. CONCLUSION： nNOS and iNOS play different roles in LPS-induced intestinal injury. Caution should be exerted concerning potential therapeutic uses of NOS inhibitors in NEC.

Anti-oxidant effect of picroside II in a rat model of cerebral ischemia/reperfusion injury

Picroside II,the major active component of picroside,has been shown to induce PC12 cell axonal growth and relieve free radical damage.In vivo experiments have demonstrated that picroside II can improve neurological function in rats with cerebral ischemia/reperfusion injuries.In the present in vivo study,enzyme-linked immunosorbent assay and immunohistochemistry revealed that picroside II increased superoxide dismutase content and reduced inducible nitric oxide synthase content in the ischemic hemisphere.The effects of picroside II were similar to those of salvianic acid A sodium,an active control drug.These results indicate that picroside II exerts a neuroprotective effect,possibly by downregulating inducible nitric oxide synthase expression,increasing superoxide dismutase activity,and inhibiting neuronal apoptosis.

Curcumin protects against ischemic spinal cord injury The pathway effect

Inducible nitric oxide synthase and N-methyI-D-aspartate receptors have been shown to participate in nerve cell injury during spinal cord ischemia. This study observed a protective effect of curcumin on ischemic spinal cord injury. Models of spinal cord ischemia were established by ligating the lumbar artery from the left renal artery to the bifurcation of the abdominal aorta. At 24 hours after model establishment, the rats were intraperitoneally injected with curcumin, Reverse transcrip- tion-polymerase chain reaction and immunohistochemical results demonstrated that after spinal cord ischemia, inducible nitric oxide synthase and N-methyI-D-aspartate receptor mRNA and protein expression significantly increased. However, curcumin significantly decreased inducible nitric oxide synthase and N-methyI-D-aspartate receptor mRNA and protein expression in the ischemic spinal cord. Tadov scale results showed that curcumin significantly improved motor function of the rat hind limb after spinal cord ischemia. The results demonstrate that curcumin exerts a neuroprotective ef- fect against ischemic spinal cord injury by decreasing inducible nitric oxide synthase and N-methyI-D-aspartate receptor expression.

Anti-cancer effect of iNOS inhibitor and its correlation with angiogenesis in gastric cancer

AIM: To observe the anti-cancer effect of iNOS selective inhibitor (aminoguanidine, AG) and investigate the relationship between iNOS inhibitor and angiogenesis, infiltration or metastasis in MFC gastric cancer xenografts.METHODS: Fifty athymic mice xenograft models were established by inoculating gastric cancer cell MFC subcutaneously. Twenty-four hours later, 0.9% sodium chloride solution, mitomycin, low dosage AG, high dosage AG, mitomycin and AG were administered by intraperitoneal injection respectively. Thus these mice were divided into five groups of 10 each randomly: control group, MMC group,AGL group, AGH group, MMC+AGH group. Two weeks later the mice were killed, and the tumor weight, inhibitory rate were evaluated. Greiss assay was used to detect the nitric oxide levels in plasma. HE and immunohistochemistry staining were used to examine microvessel density (MVD)and the expression of iNOS, VEGF, and PCNA. Apoptosis was detected by using TUNEL assay.RESULTS: The inhibitory rates in MMC+AGH group and AGH group were 52.9% and 47.1% respectively, which is significant statistically compared with that of control group (0). In treatment groups, the cell proliferation index (PI)was lower and apoptosis index was higher than those of control group. Microvessel density, iNOS, and VEGF in MMC+ AGH group were 8.8±2.6, 2.4±1.1, and 2.1±1.4respectively, which is significant statistically compared with those of control group (68.3±10.6, 11.3±1.3, and 10.3±1.6). The NO level in plasma of MMC+ AGH and AGH group were 12.7±2.1 and 12.9±2.0 μmol/L. Compared with that of control group (46.6±2.3 μmol/L), the difference is statistically significant.CONCLUSION: AG has anticancer effect on gastric cancer,and it has positive synergistic effect with chemotherapeutic drugs. It may play important inhibitory roles in angiogenesis of gastric cancer. The anticancer effect of iNOS inhibitors may include inducing cell apoptosis, suppressing cell proliferation and reducing angiogenesis.

Neuronal apoptosis and inflammatory reaction in rat models of focal cerebral ischemia following 40-minute suspended moxibustion

The treatment duration of heat-sensitive moxibustion（approximately 40 minutes on average） is longer than that of traditional suspended moxibustion.The present study investigated expression changes of three inflammatory and apoptosis-associated proteins（inducible nitric oxide synthase,cyclooxygenase-2 and caspase-3） in transient middle cerebral artery occlusion model rats following suspended moxibustion for 40 minutes,to explore the mechanisms underlying neuroprotective action of suspended moxibustion.The results indicated that suspended moxibustion at acupoint Dazhui（DU 14） for 40 minutes reduced the cortical expression of caspase-3,cyclooxygenase-2 and inducible nitric oxide synthase proteins of transient middle cerebral artery occlusion model rats,as well as decreasing infarct volume and ameliorating the neurological deficit score.Outcomes with 40 minutes of moxibustion were superior to the outcomes after suspended moxibustion for 15 minutes.

Remote ischemic preconditioning protects liver ischemia-reperfusion injury by regulating eNOS-NO pathway and liver microRNA expressions in fatty liver rats

BACKGROUND: Ischemic preconditioning (IPC) is a strategy to reduce ischemia-reperfusion (I/R) injury. The protective effect of remote ischemic preconditioning (RIPC) on liver I/R injury is not clear. This study aimed to investigate the roles of RIPC in liver I/R in fatty liver rats and the involvement of endothelial nitric oxide synthase-nitric oxide (eNOS-NO) pathway and microRNA expressions in this process. METHODS: A total of 32 fatty rats were randomly divided into the sham group, I/R group, RIPC group and RIPC+I/R group. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and nitric oxide (NO) were measured. Hematoxylin-eosin staining was used to observe histological changes of liver tissues, TUNEL to detect hepatocyte apoptosis, and immunohistochemistry assay to detect heat shock protein 70 (HSP70) expression. Western blotting was used to detect liver inducible NOS (iNOS) and eNOS protein levels and realtime quantitative polymerase chain reaction to detect miR-34a, miR-122 and miR-27b expressions. RESULTS: Compared with the sham and RIPC groups, serum ALT, AST and iNOS in liver tissue were significantly higher in other two groups, while serum NO and eNOS in liver tissue were lower, and varying degrees of edema, degeneration and inflammatory cell infiltration were found. Cell apoptosis number was slightly lower in the RIPC+I/R group than that in I/R group. Compared with the sham group, HSP70 expressions were significantly increased in other three groups (all P<0.05). Compared with the sham and RIPC groups, elevated miR-34a expressions were found in I/R and RIPC+I/R groups (P<0.05). MiR-122 and miR-27b were found significantly decreased in I/R and RIPC+I/R groups compared with the sham and RIPC groups (all P<0.05). CONCLUSION: RIPC can reduce fatty liver I/R injury by affecting the eNOS-NO pathway and liver microRNA expressions.

Inducible nitric oxide synthase polymorphism is associated with the increased risk of differentiated gastric cancer in a Japanese population

AIM： To examine the association of inducible nitric oxide synthase （iNOS） C150T polymorphism with gastric cancer, as well as with gastric atrophy and H pylori seropositivity.METHODS： A single nucleotide polymorphism of iNOS CtSOT was examined for 454 Japanese health checkup examinees （126 males and 328 females） aged 35 to 85 years without a history of cancer and 202 gastric cancer patients （134 males and 68 females） aged 33 to 94 years with pathologically confirmed diagnosis of gastric adenocarcinoma.RESULTS： The iNOS C150T polymorphism was not associated with gastric atrophy or with H pylori seropositivity. The odds ratio （OR） of the C/T ＋T/T for gastric cancer was increased without statistical significance （OR=1.19, 95% confidence interval （CI）： 0.68-2.08）. In the differentiated subgroup （n = 113）, however, the OR of the C/T genotvpe for gastric cancer was significant （OR = 2.02, 95% CI： 1.04-3.92） relative to the C/C genotype. In addition, considering the location of gastric cancer （n = 105）, there were significant differences between the controls and non-cardia group with the ORof 2.13 （95% CI： 1.08-4.18） for C/T and 1.94 （95% CI： 1.00-3.78） for C/T ＋ T/T.CONCLUSION： The iNOS C150T polymorphism is associated with the risk of H pylori-related gastric cancer in a Japanese population. This polymorphism may play an important role in increasing the risk of gastric cancer in Asian countires with the highest rates of gastric cancer.

Pathophysiology of insulin resistance and steatosis in patients with chronic viral hepatitis

Chronic hepatitis due to any cause leads to cirrhosis and end-stage liver disease.A growing body of literature has also shown that fatty liver due to overweight or obesity is a leading cause of cirrhosis.Due to the obesity epidemic,fatty liver is now a significant problem in clinical practice.Steatosis has an impact on the acceleration of liver damage in patients with chronic hepatitis due to other causes.An association between hepatitis C virus (HCV) infection,steatosis and the onset of insulin resistance has been reported.Insulin resistance is one of the leading factors for severe fibrosis in chronic HCV infections.Moreover,hyperinsulinemia has a deleterious effect on the management of chronic HCV.Response to therapy is increased by decreasing insulin resistance by weight loss or the use of thiazolidenediones or metformin.The underlying mechanisms of this complex interaction are not fully understood.A direct cytopathic effect of HCV has been suggested.The genomic structure of HCV (suggesting that some viral sequences are involved in the intracellular accumulation of triglycerides),lipid metabolism,the molecular links between the HCV core protein and lipid droplets (the core protein of HCV and its transcriptional regulatory function which induce a triglyceride accumulation in hepatocytes) and increased neolipogenesis and inhibited fatty acid degradation in mitochondria have been investigated.