Manijeh Mahdavi

Colorectal cancer (CRC), the third most common cancer in the world, has been recently rising in emerging countries due to environmental and lifestyle factors. Many of these factors are brought up by industrialization, which includes lack of physical activity, poor diet, circadian rhythm disruption, and increase in alcohol consumption. They can increase the risk of CRC by changing the colonic environment and by altering gut microbiota composition, a state referred to as gut dysbiosis. Prebiotics, which are nutrients that can help maintain intestinal microbial homeostasis and mitigate dysbiosis, could be beneficial in preventing inflammation and CRC. These nutrients can hinder the effects of dysbiosis by encouraging the growth of beneficial bacteria involved in short-chain fatty acids (SCFA) production, anti-inflammatory immunity, maintenance of the intestinal epithelial barrier, pro-apoptotic mechanisms, and other cellular mechanisms. This review aims to summarize recent reports about the implication of prebiotics, and probable mechanisms, in the prevention and treatment of CRC. Various experimental studies, specifically in gut microbiome, have effectively demonstrated the protective effect of prebiotics in the progress of CRC. Hence, comprehensive knowledge is urgent to understand the clinical applications of prebiotics in the prevention or treatment of CRC.

Published data on the relationship between pregnancy outcomes of preimplantation genetic diagnosis (PGD) in translocation carriers have implicated inconclusive results. To identify potentially eligible reports, an electronic search was conducted in several databases, including PubMed, Scopus, Web of Knowledge, and Cochrane. Pooled odd ratios (ORs) and 95% confidence intervals (Cis) were estimated based on a random-effect model to evaluate the strength of association between PGD and successful pregnancy outcome in translocation carriers. A total of six cohort studies were included in the current study. The meta-analysis of these studies revealed that the PGD method was associated with an increased successful pregnancy outcome of translocation carriers (OR = 8.58; 95%CI: 1.40–52.76). In subgroup analysis, there was no significant association according to the chromosomal translocation carrier origin and the type of translocated chromosomes, as well as country. In developed countries, the pregnancy outcome of PGD was significantly improved in translocation carriers (OR = 21.79; 95%CI: 1.93–245.52). The current meta-analysis demonstrated that the PGD method is associated with successful pregnancy outcome in both types of reciprocal and Robertsonian translocation carriers, especially in developed countries.

Polymorphisms in the C-reactive protein (CRP) genes might have crucial role in the development of metabolic syndrome (MetS). In the current comprehensive meta-analyses, we aim to provide a quantitative assessment of the association between CRP single-nucleotide polymorphisms (SNPs) and the risk of MetS. An electronic search was performed on several databases. After data extraction, random effect model was used to calculate the pooled odds ratio (OR) and 95% confidence intervals (CIs). Four independent studies including case–control, cohort, and cross-sectional methods were analyzed. Our meta-analysis indicated that CRP polymorphisms are not significantly associated with MetS (OR = 0.92, 95% CI = 0.77–1.10) with significant heterogeneity (I ² = 55.4%; p-value = 0.008). The subgroup analysis revealed that only GG has significant association with MetS (OR = 0.32, 95% CI = 0.13–0.80, p-value = 0.015) without significant heterogeneity (I ² = 0%, p-value > 0.05). In conclusion, this meta-analysis provides strong evidence that only some SNPs of CRP gene are associated with the risk for development of MetS; and this relationship does not exist in different ethnic populations.

Cystinuria is an autosomal recessive defect in reabsorptive transport of cystine and the dibasic amino acids ornithine, arginine, and lysine from renal tubule and small intestine. Mutations in two genes: SLC3A1, encoding the heavy chain rbAT of the renal cystine transport system and SLC7A9, the gene of its light chain b^{0, +} AT have a crucial role in the diseases. In our previous studies from Iranian populations with Cystinuria totally six and eleven novel mutations respectively identified in SLC3A1 and SLC7A9 genes. In this study, we conducted an in silico functional analysis to explore the possible association between these genetic mutations and Cystinuria. MutationTaster, PolyPhen-2, PANTHER, FATHMM. PhDSNP and MutPred was applied to predict the degree of pathogenicity for the missense mutations. Furthermore, Residue Interaction Network (RIN) and Intron variant analyses was performed using Cytoscape and Human Slicing Finder softwares. These genetic variants can provide a better understanding of genotype–phenotype relationships in patients with Cystinuria. In the future, the findings may also facilitate the development of new molecular diagnostic markers for the diseases.

Previous studies have reported the association of GABA receptor subunits B3, A5, and G3 single-nucleotide polymorphisms (SNPs) in chromosome 15q11–q13 with autism spectrum disorders (ASDs). However, the currently available results are inconsistent. This study aimed to investigate the association between ASD and the GABA receptor SNPs in chromosomal region 15q11–q13. The association was calculated by the overall odds ratio (OR) with a 95% confidence interval (CI). We used sensitivity analyses and the assessment of publication bias in our meta-analysis. Eight independent case-control studies involving 1408 cases and 2846 healthy controls were analyzed, namely, 8 studies for GABRB3 SNPs as well as 4 studies for GABRA5 and GABRG3 polymorphisms. The meta-analysis showed that GABRB3 polymorphisms in general are not significantly associated with autism [OR = 0.846 (95% CI): 0.595–1.201, I² = 79.1%]. Further analysis indicated that no associations were found between GABRB3 SNPs and autism on rs2081648 [OR = 0.84 (95% CI) = 0.41–1.72, I² = 89.2%] and rs1426217 [OR = 1.13 (95% CI) = 0.64–2.0, I² = 83%]. An OR of 0.95 (95% CI) = 0.77–1.17 was reported (I² = 0.0%) for GABRA5 SNPs and an OR of 0.96 (95% CI) = 0.24–3.81 was obtained from GABRG3 SNPs (I² = 97.8%). This meta-analysis provides strong evidence that different SNPs of GABA receptor B3, A5, and G3 subunit genes located on chromosome 15q11–q13 are not associated with the development of autism spectrum diseases in different ethnic populations. However, in future research, large-scale and high-quality studies are necessary to confirm the results.

Several epidemiological studies have evaluated the associations between coffee consumption and the risk of skin cancer; however, the results were not conclusive. This systematic review and meta-analysis of the cohort and case–control studies was carried out to determine the association between coffee intake and the risk of nonmelanoma skin cancer. Studies were identified by searching the PubMed and MEDLINE databases (to November 2015). Study-specific risk estimates were pooled under the random-effects model. We separately estimated the relative risk of the three conditions, for exposure to different doses of coffee consumption, kind of study design, and analysis restricted to the basal cell carcinoma type. The summary relative risks for nonmelanoma skin cancer were 0.96 [95% confidence interval (CI): 0.92–0.99] for one cup of coffee, 0.92 (95% CI: 0.88–0.97) for one to two cups of coffee, 0.89 (95% CI: 0.86–0.93) for two to three cups of coffee, and 0.81 (95% CI: 0.77–0.85) for more than three cups of coffee per day, respectively. This meta-analysis suggested that caffeinated coffee might have chemopreventive effects against basal cell carcinoma dose dependently. However, other prospective studies are warranted to confirm these effects.

Allgrove syndrome (triple A syndrome) is a rare autosomal recessive condition with adrenal insufficiency, achalasia and alacrima. This syndrome is caused by mutations in AAAS gene. In this article we introduce six patients of Allgrove syndrome, in whom genetic analysis of the triple A gene was used to identify gene mutation, DNA was extracted from blood samples. Exon 1 to 16 and some introns of the AAAS gene were amplified by polymerase chain reaction (PCR). PCR products were evaluated by complete nucleotide sequence analysis. After sequencing, alignment and analysis were carried out. In one patient we identified a IVS14 + 1 G > A mutation, which is previously reported. In 4 patients, we couldn’t detect any mutation. We determined a new mutation (c.446 + 87del T) in the AAAS gene in a patient that this deletion causes splicing defect in intron 5 which results in a premature termination and non-functional ALADIN protein. In conclusion, since molecular genetic testing results may influence the therapy and prognosis of Allgrove patients, this paper contributes to understanding of the molecular basis of Allgrove syndrome in Iranian patients. Keywords: Allgrove Syndrome; Mutation; Iran; AAAS Gene

The insulin-like growth factor-1 receptor (IGF-1R) is a transmembrane receptor with tyrosine kinase activity. The receptor plays a critical role in cancer. Using monoclonal antibodies (MAbs) against the IGF-1R, typically blocks ligand binding and enhances down-regulation of the cell-surface IGF-1R. Some MAbs such as cixutumumab are under clinical trial investigation. Targeting multiple distinct epitopes on IGF-1R, might be an effective strategy to inhibit IGF-1R pathway in cancer. In this study, new linear B cell epitopes for the extracellular domains of IGF-1R were predicted by in silico methods using a combination of linear B cell epitope prediction web servers such as ABCpred, Bepired, BCPREDs, Bcepred and Elliprro. Moreover, Discotope, B-pred and PEPOP web server tools were employed to predict new conformational B cell epitopes. In contrast to previously reported epitopes from extracellular region of the IGF-1R, we predicted new linear P8: (RQPQDGYLYRHNYCSK) and conformational Pc4: (HYYYAGVCVPACPPNTYRFE), Ppc6: (KMCPSTGKRENNESAPDNDT) and Ppc20: (ANILSAESSDSEFMQEPSGFI) epitopes. These epitopes are useful for further study as peptide antigens to actively immune host animals to develop new MAbs. Furthermore, the epitopes can be used in peptide-based cancer vaccines design.