New immunological investigations on Helicobacter pylori‐induced gastric ulcer in patients

Although Helicobacter pylori (Hp) plays an important role in the pathogenesis of chronic gastritis and gastric ulcer, little is known about the probable mechanisms of these types of gastrointestinal damage. To determine the precise mechanisms involved in ulcer formation, immune responses in patients with gastric ulcer (GUP) caused by Hp infection (Hp⁺) were compared with those of other gastritis patients (GP). The sensitivity and proliferation of peripheral blood mononuclear cells (PBMNCs) obtained from patients were evaluated by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay against exposure with complex Hp crude antigen (HPCA) and mitogen (phytohemagglutinin, PHA). Production of inflammatory cytokines, including interleukin (IL)‐1β and IL‐8, in serum and supernatants of PBMNCs were then measured by ELISA. It was found that, after stimulation with PHA, both IL‐8 and IL‐1β concentrations in sera and supernatants as well as proliferation and sensitivity were statistically greater in GUP Hp⁺ than GP Hp^?. Furthermore, HPCA inhibited the proliferation of PBMNCs dose‐dependently; however, it stimulated IL‐8 and IL‐1β production in supernatants of mononuclear cells. Therefore, the up‐regulated concentrations of IL‐8 and IL‐1β may have been caused by increase in the size of mononuclear cell subpopulations or in their cytokine secretory activity, indicating the greatest cell responsiveness in GUP Hp⁺ patients. These results suggest that tissue damage and ulcers occur in patients who produce more IL‐8 and IL‐1β than patients who do not develop ulcers; the former consequently have more activated immune cells at the site of infection. Therefore, both host responses and Hp virulence factors may be involved in the development of gastric ulcers.

     

Effects of Heracleum persicum ethyl acetate extract on the growth, hyphal ultrastructure and aflatoxin biosynthesis in Aspergillus parasiticus

The ethyl acetate extract of leaves, seeds and flowers of Heracleum persicum, a medicinal plant of Iran (family Apiaceae) inhibited growth and aflatoxin (AF) production of Aspergillus parasiticus. On the basis of total dry weight growth inhibition by the leaf extract ranged from 17.1 to 36.9 %, by the flower extract from 32.2 to 75.6 %, and by the seed extract from 27.5 to 74.9 %. Production of AFB₁ and AFG₁ was inhibited in a dose-dependent manner, with a reduction of 88.5–100 % at the highest concentration of 8,000 μg/ml tested. The flower extract decreased ergosterol content of hyphae most significantly. Electron microscopy further revealed structural defects in the treated A. parasiticus including disruption of cytoplasmic membranous compartments, detachment of plasma membrane from the cell wall, and disorganization of hyphal compartments. Collapsed hyphae without conidiation, shorter branches and undifferentiated hyphal tips were also evident. The results indicate that H. persicum extract exerts antifungal and anti-AF activities by disrupting plasma membrane integrity and permeability mainly through interference with ergosterol biosynthesis. These results show that H. persicum can serve as a potent and safe alternative for inhibiting toxigenic aspergilli growth and thus preventing AF contamination of foods and feeds.     

Effect of bisphenols on telomerase expression and activity in breast cancer cell lines

Molecular Biology Reports - Bisphenol A (BPA), a monomer of polycarbonates and resins, was shown to induce the expression of telomerase enzyme which has been associated with breast cancer...     

Leishmania major: low infection dose causes short-lived hyperalgesia and cytokines upregulation in mice

Neural involvement was traditionally associated with leprosy. However, more recent studies have shown the presence of a persistent hyperalgesia in cutaneous leishmaniasis caused by the infection of BALB/c mice with a high dose of Leishmania major. In this study, we report the presence of hyperalgesia within the first two weeks of infection caused by a low dose of the parasite. Using BALB/c mice, we demonstrate the presence of hyperalgesia during the first 10 days of infection as assessed by thermal pain tests. After 10 days these decreased pain thresholds start to recover resulting in similar levels to those in uninfected controls during the third week of infection. This hyperalgesia is accompanied by a sustained upregulation of interleukin-1beta (IL-1beta) and an early upregulation of interleukin-6 (IL-6) which is restored to normal levels after five days of infection. In conclusion, this study shows that, during early infection, the low dose of L. major causes hyperalgesia accompanied by an upregulation of IL-1beta and IL-6 and that these effects are reversed within the first two weeks of infection.     

The ?4817 G>A (rs2238136) variant of the vitamin D receptor gene: a probable risk factor for colorectal cancer

Vitamin D appears to have anti-tumor activities in the large bowel. Our aim was to investigate whether -4817 G>A (rs2238136) polymorphism located at 5'-untranslated region (5'-UTR) of the human vitamin D receptor (VDR) gene was associated with colorectal cancer (CRC) risk. We conducted a case-control study and VDR genotypes, determined by Bpu10I restriction endonuclease digestion of PCR-amplified DNA, were performed on 327 cases with CRC and 327 controls. The distribution of VDR -4817 G>A genotypes and alleles differed significantly between cases with CRC and controls even after adjustment for confounding factors such as age, BMI, sex, and smoking status. Individuals carrying the "AA" genotype had a 2.09-fold increased risk compared with those with "GG" genotype (P?=?0.016, OR?=?2.09, 95% CI?=?1.15-3.78) and a 1.87-fold increased risk compared with those with "GG and GA" genotypes (P?=?0.033, OR?=?1.87, 95% CI?=?1.05-3.33) for CRC. Furthermore, the VDR "A" allele was significantly overrepresented in cases with CRC than controls (P?=?0.044; OR?=?1.28, 95% CI?=?1.01-1.63). Interestingly, the analysis of the SNP revealed that all these associations were stronger for women subjects than for all subjects combined. These data indicated for the first time a direct association between "AA" genotype of VDR gene -4817 G>A polymorphism and CRC, with a stronger association for female subjects. However, our findings remain to be confirmed in other populations.     

Improving salinity tolerance of plants through conventional breeding and genetic engineering: An analytical comparison

The last century has witnessed a substantial improvement in yield potential, quality and disease resistance in crops. This was indeed the outcome of conventional breeding, which was achieved with little or no knowledge of underlying physiological and biochemical phenomena related to a trait. Also the resources utilized on programs involving conventional breeding were not of great magnitude. Plant breeders have also been successful during the last century in producing a few salt-tolerant cultivars/lines of some potential crops through conventional breeding, but this again has utilized modest resources. However, this approach seems now inefficient due to a number of reasons, and alternatively, genetic engineering for improving crop salt tolerance is being actively followed these days by the plant scientists, world-over. A large number of transgenic lines with enhanced salt tolerance of different crops can be deciphered from the literature but up to now only a very few field-tested cultivars/lines are known despite the fact that considerable resources have been expended on the sophisticated protocols employed for generating such transgenics. This review analytically compares the achievements made so far in terms of producing salt-tolerant lines/cultivars through conventional breeding or genetic engineering.     

Proteomic analysis of plasma from patients with systemic lupus erythematosus: increased presence of haptoglobin alpha2 polypeptide chains over the alpha1 isoforms

In the present study plasma samples from 15 systemic lupus erythematosus (SLE) patients and 16 healthy controls of initially unknown haptoglobin (Hp) phenotype were separated by 2-DE, and tryptic digests of the excised Hpalpha polypeptide chain spots were analyzed by MALDI-TOF-MS. Selected tryptic peptides were sequenced by nano-(n)ESI-IT MS/MS. The six major Hp phenotypes were present, although with distinct frequencies in controls and SLE patients. Thus, there were an increased proportion of SLE patients with Hp 2-2, or Hp 2-1S phenotypes. The Hp phenotype distribution resulted in allele frequencies of 0 625 (Hp(2)), 0.281 (Hp(1S)), and 0.093 (Hp(1F)) in healthy controls, correlating fairly well with the allele frequencies of European populations. In contrast, the Hp allele frequencies of the SLE patients were 0.733 (Hp(2)), 0.233 (Hp(1S)), and 0.033 (Hp1(1F)), which clearly indicated an increased frequency of Hp(2), a similar proportion of Hp(1S) and a diminished proportion of Hp(1F) in SLE patients compared with that in healthy controls. Preferential Hpalpha2 expression in SLE patients may contribute to some of the clinical manifestations of the disease such as hypergammaglobulinemia, systemic vasculitis, and cardiovascular disorders.     

Soil water availability for plants as quantified by conventional available water, least limiting water range and integral water capacity

There are different approaches to define the soil available water (SAW) for plants. The objectives of this study are to evaluate the SAW values of 12 arable soils from Hamadan province (western Iran) calculated by plant available water (PAW), least limiting water range (LLWR) and integral water capacity (IWC) approaches and to explore their relations with Dexter’s index of soil physical quality (i.e., S-value). Soil water retention and mechanical resistance were determined on the intact samples which were taken from the 5–10 cm layer. For calculation of LLWR and IWC, the van Genuchten-Mualem model was fitted to the observed soil water retention data. Two matric suctions (h) of 100 and 330 cm were used for the field capacity (FC). There were significant differences (P?<?0.01) between the SAW values calculated by PAW₁₀₀, PAW₃₃₀, LLWR₁₀₀, LLWR₃₃₀ and IWC. The highest (i.e., 0.210 cm³ cm^?3) and the lowest (i.e., 0.129 cm³ cm^?3) means of SAW were calculated for the IWC and LLWR₃₃₀, respectively. The upper limit of LLWR₃₃₀ for all of the soils was h of 330 cm, and that of LLWR₁₀₀ (except for one soil that was air-filled porosity of 0.1 cm³ cm^?3) was h of 100 cm. The lower limit of LLWR₃₃₀ and LLWR₁₀₀ for five soils was h of 15,000 cm and for seven soils was mechanical resistance of 2 MPa. The IWC values were smaller than those of LLWR₁₀₀ for two soils, equal to those of LLWR₁₀₀ for three soils and greater than those of LLWR₁₀₀ for the rest. There is, therefore, a tendency to predict more SAW using the IWC approach than with the LLWR approach. This is due to the chosen critical soil limits and gradual changes of soil limitations vs. water content in the IWC calculation procedure. Significant relationships of SAW with bulk density or relative bulk density were found but not with the clay and organic matter contents. Linear relations between IWC and LLWR₁₀₀ or LLWR₃₃₀ were found as: IWC?=??0.0514 + 1.4438LLWR₁₀₀, R ²?=?0.83; and IWC?=??0.0405 + 2.0465LLWR₃₃₀, R ²?=?0.84, respectively (both significant at P?<?0.01). Significant relationships were obtained between the SAW values and S indicating the suitability of the index S to explain the availability of soil water for plants even when complicated approaches like IWC are considered. Overall, the results demonstrate the importance of the choice of the approach to be used and its critical limits in the estimation of the soil available water to plants.     

Regulation of protein kinase C Apl II by serotonin receptors in Aplysia

Serotonin (5-hydroxytryptamine, 5HT) is the neurotransmitter that mediates dishabituation in Aplysia. Serotonin mediates this behavioral change through the reversal of synaptic depression in sensory neurons (SNs). However, the 5HT receptors present in SNs and in particular, the receptor important for activation of protein kinase C (PKC) have not been fully identified. Using a recent genome assembly of Aplysia, we identified new receptors from the 5HT(2) , 5HT(4) , and 5HT(7) families. Using RT-PCR from isolated SNs, we found that three 5HT receptors, 5HT(1Apl(a)) , 5HT(2Apl) , and 5HT(7Apl) were expressed in SNs. These receptors were cloned and expressed in a heterologous system. In this system, 5HT(2Apl) could significantly translocate PKC Apl II in response to 5HT and this was blocked by pirenperone, a 5HT(2) receptor antagonist. Surprisingly, pirenperone did not block 5HT-mediated translocation of PKC Apl II in SNs, nor 5HT-mediated reversal of depression. Expression of 5HT(1Apl(a)) in SNs or genistein, an inhibitor of tyrosine kinases inhibited both PKC translocation and reversal of depression. These results suggest a non-canonical mechanism for the translocation of PKC Apl II in SNs.