Polymorphism in the interleukin-17A promoter contributes to gastric cancer

AIM:To evaluate the contribution of the G-197A polymorphism in the interleukin-17(IL-17)promoter region to gastric cancer risk in an Iranian population.METHODS:We performed a case control study using samples from 161 individuals with gastric cancer and171 healthy controls.For each individual,the G-197A genotype was determined by restriction fragment length polymorphism analysis of polymerase chain reaction-amplified fragments.Statistical analyses were performed to determine whether any demographic or behavioral factors,infection with Helicobacter pylori(H.pylori),or a particular G-197A genotype was associated with gastric cancer risk.RESULTS:We found that the G-197A genotype wassignificantly associated with increased gastric cancer risk(P=0.001).Patients who were homozygous(AA)at position-197 were 2.9 times more likely to develop disease(95%CI:1.56-5.4;P=0.001).Furthermore,logistic regression analysis revealed that the presence of a single A allele increased the risk of gastric cancer up to 1.7-fold(95%CI:1.26-2.369;P=0.001).This association was observed for early stage gastric adenocarcinomas only,and was not linked to H.pylori infection.CONCLUSION:These results suggest that carrying one or more G-197A polymorphisms at position-197 in the IL-17 promoter region significantly increases gastric cancer risk in this patient population.

Inducible nitric oxide synthetase genotype and Helicobacter pylori infection affect gastric cancer risk

AIM:To investigate the association of the inducible nitric oxide synthetase(iNOS) C150T polymorphism with Helicobacter pylori(H.pylori) infection and gastric cancer(GC) risk in Iran.METHODS:In order to determine whether there was a correlation between iNOS genotype and GC in Iran,we conducted a case-control study using samples from 329 individuals.For each sample,the C150T iNOS polymorphism was genotyped by polymerase chain reaction(PCR) and restriction digestion.Patients were grouped by cancer presence,demographic and behavior characteristics,and H.pylori infection status.Statistical tests were conducted to determine whether any behavioral factors or a particular iNOS genotype was associated with GC in the study population.RESULTS:In this population,we found that smoking,hot beverage consumption,a familial history of GC and H.pylori infection status were significantly associated with GC development(P = 0.015,P < 0.001,P = 0.0034,and P < 0.015,respectively).The distribution of the C150T iNOS genotypes among the two study groups was not statistically significant alone,but was impacted by H.pylori infection status.When compared to the non-H.pylori infected group,cancer patients who had a heterozygous CT genotype and were also infected with H.pylori were 2.1 times more at risk of developing GC [odds ratio(OR) = 2.1,P = 0.03] while those with a homozygous TT genotype and infected with H.pylori were 5.0 times more at risk of developing GC(OR = 5.0,P = 0.029).In contrast,this association was not seen in patients in the control group.CONCLUSION:A CT or TT polymorphism at position 150 in the iNOS gene significantly increases the risk of GC and may be a marker for GC susceptibility.

Serum immunoglobulin A concentration is a reliable biomarker for liver fibrosis in non-alcoholic fatty liver disease

AIM:To evaluate the diagnostic accuracy of serum Immunoglobulin A(IgA)for differentiating early stage nonalcoholic fatty liver disease(NAFLD)from nonalcoholic steatohepatitis(NASH).METHODS:All cases had fatty liver change confirmed by ultrasound and aminotransferases of at least twice the normal level.Clinical and biochemical data,including serum IgA,were obtained from 50 histologically proven NAFLD cases and 54 healthy controls.Fasting whole blood samples were obtained from the study population.Immunoturbidimetric methods were used to measure the IgA levels.All NAFLD cases were hospitalized for liver biopsy.Liver specimens were examined for steatosis,steatohepatitis and fibrosis within hepatocytes.Patients were categorized into two groups:NASH and non-NASH.Variables were compared within cases(NASH vs non-NASH)and controls.Cut-off values of serum IgA were evaluated using analysis of receiver operating characteristic(ROC curves).Associations between the variables were tested using calculations of correlation coefficients.Statistical significances were assigned to P values<0.05.RESULTS:The extent of liver fibrosis correlated positively with IgA levels.Subjects with no fibrosis in their liver biopsies had a lower IgA level(301.5±91.2 mg/dL)than subjects with any degree of fibrosis(388.8±140.8 mg/dL),(P=0.01).IgA levels were higher in NASH cases,and its value was significantly higher for higher degrees of fibrosis.Patients with perisinusoidal or pericellular fibrosis had significantly higher levels of IgA(403.5±133.9 mg/dL,418.2±129.5 mg/dL)compared to those without it(301.8±94.9 mg/dL,297.7±91.5 mg/dL),respectively.No significant correlation was found between steatosis grade and serum IgA levels.Based on ROC analysis,the best predictive IgA cutoff value for detecting liver fibrosis was 360mg/dL(61%sensitivity,81%specificity).CONCLUSION:The serum IgA level is useful to evaluate the severity of liver fibrosis and can be used serially for evaluation and follow-up of NAFLD cases.

Effect of land-use changes on chemical and physical properties of soil in western Iran(Zagros oak forests)

The consequence of land-use change from forest to agriculture and other uses has become one of the world’s greatest concerns.The soil,one of the most important components of forests and containing all the required plant nutrients as soluble ions,is highly impacted by these changes.Because vast areas of the Zagros forests in western Iran have changed in use during the last few decades,the present study investigated the effects of landuse changes of forest area to agriculture,orchard,and agroforestry on soil chemical and physical properties.Soil was sampled at four land-use areas:less-disturbed forest areas(control)and agricultural,orchard,and agroforestry areas.Among each of the two forest-use areas(agroforestry and orchard),we selected five trees with similar-sized crowns and sampled under each tree crown at 0-15 and>15-30 cm depths.Five soil samples also were taken in agriculture area at each depth.The findings indicated that during land-use changes,soil sand particles decreased,and clay and silt particles of soil increased,resulting in a fine soil texture.Moreover,the amount of nitrogen(N),phosphorus(P),organic carbon(OC),and electrical conductivity(EC)of soil decreased at both depths due to the decrease in organic matter.Soil pH and magnesium(Mg)level rose during land-use change at both depths except at agricultural sites.Soil potassium(K)content decreased during agricultural use due to the elimination of tree cover.The level of K decreased only at the depth of 0-15 cm because of K dependency on parent materials.Generally,most soil nutrients were affected by plant removal in the conversion.Forest and agricultural soil are distinguishable by their properties,while land-uses such as agroforestry-orchard separated from the others.Soil nutrients were severely affected by the decrease and elimination of tree cover,plowing,and continuous harvesting,resulting in a decline in soil quality and fertility.

Effects of Persian turpentine tree litter and slope aspect on soil chemical properties in a Zagros forest,Iran

For analyzing the effects of forest litter and slope aspect on soil properties eight soil samples were collected at a depth of 0–10 cm near(i.e.,beneath the crown)and away from(i.e.,not influenced by crown)five Persian turpentine trees each on a north and a south slope at the same elevation in a Zagros forest,Iran.The litter beneath tree crowns and slope exposure were found to have significant interactive effects on C,N,P,K,and electrical conductivity of the soils,however,Ca,Mg and the soil pH were not significantly influenced by these factors.The soil beneath the crowns was enriched in cations compared to more distal positions.Generally,Persian turpentine trees have positive impacts on soil properties in the forest.Degrading or killing these trees by sap extraction,extreme grazing,cutting,fire and expansion of agriculture will lead to significant losses in soil fertility and increases in soil erosion.

Structure-activity relationship of pyrazol-4-ylpyridine derivatives and identification of a radiofluorinated probe for imaging the muscarinic acetylcholine receptor M4

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor4(M4)in schizophrenia and dementia with Lewy bodies,however,a clinically validated M4positron emission tomography(PET)radioligand is currently lacking.As such,the aim of this study was to develop a suitable M4PET ligand that allows the non-invasive visualization of M4in the brain.Structure-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12—a subtype-selective positive allosteric modulator(PAM).The radiofluorinated analogue,[18F]12,was synthesized in 28±10%radiochemical yield,>37 GBq/μmol and an excellent radiochemical purity>99%.Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of[18F]12 for the M4-rich striatum.However,in the presence of carbachol,a significant increase in tracer binding was observed in the rat striatum,which was reduced by>60%under blocking conditions,thus indicating that orthosteric ligand interaction is required for efficient binding o f[18F]12 to the allosteric site.Remarkably,however,the presence of carbachol was not required for high specific binding in the non-human primate(NHP)and human striatum,and did not further improve the specificity and selectivity of[18F]12 in higher species.These results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP,where peak brain uptake of[18F]12 was found in the putamen and temporal cortex.In conclusion,we report on the identification and preclinical development of the first radiofluorinated M4PET radioligand with promising attributes.The availability of a clinically validated M4PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.