Comprehensive analysis of 5-aminolevulinic acid dehydrogenase (ALAD) variants and renal cell carcinoma risk among individuals exposed to lead

Background

Epidemiologic studies are reporting associations between lead exposure and human cancers. A polymorphism in the 5-aminolevulinic acid dehydratase (ALAD) gene affects lead toxicokinetics and may modify the adverse effects of lead.

Methods

The objective of this study was to evaluate single-nucleotide polymorphisms (SNPs) tagging the ALAD region among renal cancer cases and controls to determine whether genetic variation alters the relationship between lead and renal cancer. Occupational exposure to lead and risk of cancer was examined in a case-control study of renal cell carcinoma (RCC). Comprehensive analysis of variation across the ALAD gene was assessed using a tagging SNP approach among 987 cases and 1298 controls. Occupational lead exposure was estimated using questionnaire-based exposure assessment and expert review. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression.

Results

The adjusted risk associated with the ALAD variant rs8177796^CT/TT was increased (OR = 1.35, 95%CI = 1.05–1.73, p-value = 0.02) when compared to the major allele, regardless of lead exposure. Joint effects of lead and ALAD rs2761016 suggest an increased RCC risk for the homozygous wild-type and heterozygous alleles (^GGOR = 2.68, 95%CI = 1.17–6.12, p = 0.01; ^GAOR = 1.79, 95%CI = 1.06–3.04 with an interaction approaching significance (p_int = 0.06).. No significant modification in RCC risk was observed for the functional variant rs1800435^(K68N). Haplotype analysis identified a region associated with risk supporting tagging SNP results.

Conclusion

A common genetic variation in ALAD may alter the risk of RCC overall, and among individuals occupationally exposed to lead. Further work in larger exposed populations is warranted to determine if ALAD modifies RCC risk associated with lead exposure.     

Rat lung decellularization using chemical detergents for lung tissue engineering

Although pulmonary diseases account for a large number of deaths in the world, most have no treatment other than transplantation. New therapeutic methods for lung treatment include lung tissue engineering and regenerative medicine. Lung decellularization has been used to produce an appropriate scaffold for recellularization and implantation. We investigated 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) with sodium dodecyl sulfate (SDS) and Triton X-100 detergents for effecting rat lung decellularization. We evaluated using conventional histology, immunofluorescence staining and SEM methods for removing nuclear material while leaving intact extracellular matrix proteins and three-dimensional architecture. We investigated different concentrations of CHAPS, SDS and Triton X-100 for different periods. We found that 2 mM CHAPS + 0/1% SDS for 48 h was the best among the treatments investigated. Our method can be used to produce an appropriate scaffold for recellularization by stem cells and for investigations ex vivo and in vivo.     

Findings on the Phytoextraction and Phytostabilization of Soils Contaminated with Heavy Metals

As a result of human activities such as mining, metal pollution has become one of the most serious environmental problems today. Phytoremediation, an emerging cost-effective, non-intrusive, and aesthetically pleasing technology that uses the remarkable ability of plants to concentrate elements can be potentially used to remediate metal-contaminated sites. The aim of this work was to assess the extent of metal accumulation by plants found in a mining area in Hamedan province with the ultimate goal of finding suitable plants for phytoextraction and phytostabilization (two processes of phytoremediation). To this purpose, shoots and roots of the 12 plant species and the associated soil samples were collected and analyzed by measurement of total concentrations of some elements (Fe, Mn, Zn, and Cu) using atomic absorption spectrophotometer and then biological absorption coefficient, bioconcentration factor, and translocation factor parameters calculated for each element. Our results showed that none of the plants were suitable for phytoextraction and phytostabilization of Fe, Zn, and Cu, while Chenopodium botrys, Stipa barbata, Cousinia bijarensis, Scariola orientalis, Chondrila juncea, and Verbascum speciosum, with a high biological absorption coefficient for Mn, were suitable for phytoextraction of Mn, and C. bijarensis, C. juncea, V. speciosum, S. orientalis, C. botrys, and S. barbata, with a high bioconcentration factor and low translocation factor for Mn, had the potential for the phytostabilization of this element.     

The role of IL15 gene variants in visceral leishmaniasis among Iranian patients

The role of IL-15 in the protection against Leishmania (L) parasites has been clarified in previous studies, in which IL-15 similar to IFN-γ induces IL-12 production and stimulates the leishmaniacidal activity of the macrophages infected with L. infantum. Furthermore, the increased level of IL-15 in acute visceral leishmaniasis patients (VL) can suppress Th2 cytokines such as IL-4. Since different single nucleotide polymorphisms (SNPs) in the IL15 gene have been described, this study aimed to investigate the association of the SNPs at the positions 267, 367, 13,687 and 14,035 with VL. The IL15 gene variants were compared between two groups consisting of 117 VL patients and 146 healthy individuals using polymerase chain reaction-restriction fragment length polymorphism. The results showed that the frequencies of the alleles 267C (83.9 vs. 73.5 %, P = 0.0035), 13687A (22.4 vs. 12.8 %, P = 0.032), genotype 267CC (68.5 vs. 55.6 %, P = 0.031), haplotypes CGCA (16 vs. 8.3 %, P = 0.02) and TACA (11.2 vs. 4.8 %, P = 0.02) were significantly higher in the controls than those in the patients, while the genotypes 267TT (8.5 vs. 0.7 %, P = 0.0016), 13687CC (78.6 vs. 65.5 %, P = 0.015), the haplotypes TGCT (10 vs. 2.5 %, P = 0.00002) and TGCA (5.7 vs. 0.35 %, P = 0.000001) were significantly more frequent in the patients. In conclusion, it may be speculated that these gene variants with probable effects on the IL-15 production can serve as the factors influencing VL among Iranian population. However, to clarify the association of these variants with the level of IL-15, further studies are recommended.     

Enhanced h6h transcript level,antioxidant activity and tropane alkaloid production in Hyoscyamus reticulatus L. hairy roots elicited by acetylsalicylic acid

Hyoscyamine (Hyos) and scopolamine (SCP) are drugs widely used as antimuscarinic to treat diseases such as Parkinson’s or to calm schizoid patients. In this study, with the aim of enhancing tropane alkaloid production in H. reticulatus hairy root cultures, the effects of the signalling molecule acetylsalicylic acid (ASA) were investigated at different concentrations (0, 0.01, 0.1 and 1 mM) and inoculation times (24 and 48 h). As well as reducing biomass production, ASA treatment significantly enhanced the activity of catalase, guaiacol peroxidase and ascorbate peroxidase (p < 0.01), which was highest at 48 h of exposure to 1 mM of ASA. The highest accumulation of Hyos and SCP (1.6- and 3.5-fold more than in the control, respectively) was obtained at 24 h of exposure to 0.1 mM ASA. Additionally, semi-quantitative RT-PCR analysis showed an increased expression of the hyoscyamine-6-beta-hydroxylase (h6h) gene, involved in the last Hyos and SCP biosynthetic step, which correlated with the enhanced level of Hyos and SCP production under ASA elicitation. Our findings suggest that ASA, by stimulating the expression of key biosynthetic genes and enzymes, can be applied to increase commercial tropane alkaloid production in a H. reticulatus hairy root system.     

Evaluation of Oxidative Stress,Apoptosis, and Expression of MicroRNA-208a and MicroRNA-1 in Cardiovascular Patients

Background:MicroRNA expression signature and reactive oxygen species (ROS) production have been associated with the development of cardiovascular diseases (CVDs). This study aimed to evaluate oxidative stress, inflammation, apoptosis, and the expression of miRNA-208a and miRNA-1 in cardiovascular patients.Methods:The study population included four types of patients (acute coronary syndromes (ACS), myocardial infarction (MI), arrhythmia, and heart failure (HF)), with 10 people in each group, as well as a control group. Quantitative real-time PCR was performed to measure mir-208 and miR-1 expression, the mRNAs of inflammatory mediators (TNFα, iNOS/eNOS), and apoptotic factors (Bax and Bcl2). XOX, MDA, and antioxidant enzymes (CAT, SOD, and GPx) were measured by ZellBio GmbH kits by an ELISA Reader.Results:The results showed significant decreases in the activity of antioxidant enzymes (CAT, SOD, and Gpx) and a significant increase in the activity of the MDA and XOX in cardiovascular patients. Significant increases in IL-10, iNos, iNOS / eNOS, and TNF-α in cardiovascular patients were also observed. Also, a significant increase in the expression of miR-208 (HF> arrhythmia> ACS> MI) and a significant decrease in the expression of miR-1 (ACS> arrhythmia> HF> MI) were found in all four groups in cardiovascular patients.Conclusion:The results showed increases in oxidative stress, inflammation, apoptotic factors, and in the expression of miR-208a in a variety of cardiovascular patients (ACS, MI, arrhythmia, and HF). It is suggested that future studies determine the relationships that miR-1, miR-208, and oxidative stress indices have with inflammation and apoptosis.Key Words: Apoptosis, Cardiovascular diseases, Inflammation, microRNA-208a, microRNA-1, Oxidative stress     

Parasitism capacity and searching efficiency of Diaeretiella rapae parasitizing Brevicoryne brassicae on susceptible and resistant canola cultivars

Different cultivars of aplant species can affect the foraging and efficiency of natural enemies, both directly through physical and biochemical properties or indirectly through the herbivore's diet. In this study, the parasitism capacity and functional response of Diaeretiella rapae McIntosh were determined on the cabbage aphid, Brevicoryne brassicae (L.) reared on susceptible (Opera) and resistant (Okapi) canola cultivars under laboratory conditions at 25?±?1?°C, 60?±?5% RH and a16:8?h L:D photoperiod. The parasitoid exhibited Type II and Type III functional responses on the resistant and susceptible cultivars, respectively. The estimated value of searching efficiency (a) was 0.1637?±?0.1095?h^?1 on the resistant cultivar whereas its value was dependent on host density on the susceptible cultivar. The handling times (T_h) on the susceptible and resistant canola cultivars were 0.108?±?0.040 and 0.320?±?0.048?h, respectively. The net parasitism rate (C₀) of the parasitoid wasp varied from 128.09 hosts per parasitoid lifetime on the susceptible to 71.01hosts on the resistant canola cultivar. The transformation rate from host population to parasitoid offspring (Qp) was equal to 1 on both cultivars (C₀?=?R₀). The finite parasitism rate (ω) on the susceptible cultivar (0.819 hosts per parasitoid per day) was significantly higher than that on the resistant one (0.578 hosts per parasitoid per day). In conclusion, canola cultivars affected the performance of D. rapae in controlled small-scale laboratory experiments and compared with the susceptible cultivar, the resistant one had anadverseeffect on the efficiency of the parasitoid.     

LINE1 methylation levels associated with increased bladder cancer risk in pre-diagnostic blood DNA among US (PLCO) and European (ATBC) cohort study participants

Global methylation in blood DNA has been associated with bladder cancer risk in case-control studies, but has not been examined prospectively. We examined the association between LINE1 total percent 5-methylcytosine and bladder cancer risk using pre-diagnostic blood DNA from the United States-based, Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO) (299 cases/676 controls), and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) cohort of Finnish male smokers (391 cases/778 controls). Logistic regression adjusted for age at blood draw, study center, pack-years of smoking, and sex was used to estimate odd ratios (ORs) and 95% confidence intervals (CIs) using study- and sex-specific methylation quartiles. In PLCO, higher, although non-significant, bladder cancer risks were observed for participants in the highest three quartiles (Q2–Q4) compared with the lowest quartile (Q1) (OR = 1.36, 95% CI: 0.96 -1.92). The association was stronger in males (Q2–Q4 vs. Q1 OR = 1.48, 95% CI: 1.00–2.20) and statistically significant among male smokers (Q2–Q4 vs. Q1 OR = 1.83, 95% CI: 1.14–2.95). No association was found among females or female smokers. Findings for male smokers were validated in ATBC (Q2–Q4 vs. Q1: OR = 2.31, 95% CI: 1.62–3.30) and a highly significant trend was observed (P = 8.7 × 10⁻⁷). After determining that study data could be combined, pooled analysis of PLCO and ATBC male smokers (580 cases/1119 controls), ORs were significantly higher in Q2-Q4 compared with Q1 (OR = 2.03, 95% CI: 1.52–2.72), and a trend across quartiles was observed (P = 0.0001). These findings suggest that higher global methylation levels prior to diagnosis may increase bladder cancer risk, particularly among male smokers.