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The nitric oxide (NO) pathway contributes to the pathogeneses of metabolic syndrome (MetS) and asthma. NOS2 encodes inducible-NO synthase, which is an important enzyme of the pathway, and its variations could affect the risk of asthma and MetS and thereby co-susceptibility to them. This study aims to estimate the association of NOS2-c.1823C>T with risk of asthma, MetS, and asthma with MetS condition (ASMetS), and with asthma stages: intermittent, mild, moderate, and severe asthma. The study included asthmatics ( n = 555), MetS ( n = 334), and ASMetS cases ( n = 232) and 351 controls, which were genotyped by the PCR-RFLP method. The T allele was significantly associated with an increased risk of asthma and MetS in the sample population and females. CT genotype and CT+TT model were significantly associated with increased risk of ASMetS in females. A significant association between CT genotype and increased risk of ASMetS in the sample population and females was found in ASMetS versus MetS. In the sample population and among females, the T allele was significantly associated with severe asthma. The rs2297518 single nucleotide polymorphism of NOS2 contributes to the risk of MetS, asthma, and co-susceptibility to them, and this contribution may be stronger in females compared to males.

Mushrooms in the genus Ganoderma have been collected and used as medicine since ancient times. However, commercial basidiome production has only recently been achieved. The solid substrates for basidiome production usually consist of lignocellulosic materials as the major component and the supplements (e.g., different types of bran and flour) as the minor segment. Research on substrates for solid-state fermentation with the purpose of basidiome production has focused on investigating locally available agrowaste materials, and their suitability is judged by the economic outputs. This review summarizes the formulations of the substrates and discusses their effects on the yield of basidiome or its bioactive compounds. Through a comprehensive look, this review concludes that future research focused on various treatments to modulate extracellular enzyme production may bring more options to the table for innovative solid substrate formulation.

Long non-coding RNAs (lncRNA) have been emerged as a novel class of molecular regulators in cancer. They are dysregulated in many types of cancer; however, there is not enough knowledge available on their expression and functional profiles. Lung cancer is the leading cause of the cancer deaths worldwide. Generally, lncRNAs may be associated with lung tumor pathogenesis and they may act as biomarkers for the cancer prognosis and diagnosis. Compared to other invasive prognostic and diagnostic methods, detection of lncRNAs might be a user-friendly and noninvasive method. In this review article, we selected 27 tumor-associated lncRNAs by literature reviewing to further discussing in detail for using as diagnostic and prognostic biomarkers in lung cancer. Also, in an in silico target analysis, the "Experimentally supported functional regulation" approach of the LncTarD web tool was used to identifying the target genes and regulatory mechanisms of the selected lncRNAs. The reports on diagnostic and prognostic potential of all selected lncRNAs were discussed. However, the target genes and regulatory mechanisms of the 22 lncRNAs were identified by in silico analysis and we found the pathways that are controlled by each target group of lncRNAs. They use epigenetic mechanisms, ceRNA mechanisms, protein interaction and sponge mechanism. Also, 10, 23, 5, and 28 target genes for each of these mechanisms were identified, respectively. Finally, each group of target genes controls 50, 12, 7, and 2 molecular pathways, respectively. In conclusion, LncRNAs could be used as biomarkers in lung cancer due to their roles in control of several signaling pathways related to lung tumors. Also, it seems that lncRNAs, which use epigenetic mechanisms for modulating a large number of pathways, could be considered as important subjects for lung cancer-related diagnostic and prognostic biomarkers.

The photo-physical properties of metal nano clusters are sensitive to their surrounding medium. Fluorescence enhancement, quenching, and changes in the emitted photon properties are usual events in the sensing applications using these nano materials. Combining this sensitivity with unique properties of self-assembled structures opens new opportunities for sensing applications. Here, we synthesized gold nanoclusters by utilizing phenylalanine amino acid as both capping and reducing molecule. Phenylalanine is able to self-assemble to rod-shaped nano structure in which the π-π interaction between the aromatic rings is a major stabilizing force. Any substance as iodide anion or molecule that is able to weaken this interaction influence the fluorescence of metal nano-clusters. Since the building blocks of the self-assembled structure are made through the reaction of gold ions and phenylalanine, the oxidized products and their effect of sensing features are explored.

The photo-physical properties of metal nano clusters are sensitive to their surrounding medium. Fluorescence enhancement, quenching, and changes in the emitted photon properties are usual events in the sensing applications using these nano materials. Combining this sensitivity with unique properties of self-assembled structures opens new opportunities for sensing applications. Here, we synthesized gold nanoclusters by utilizing phenylalanine amino acid as both capping and reducing molecule. Phenylalanine is able to self-assemble to rod-shaped nano structure in which the π–π interaction between the aromatic rings is a major stabilizing force. Any substance as iodide anion or molecule that is able to weaken this interaction influence the fluorescence of metal nano-clusters. Since the building blocks of the self-assembled structure are made through the reaction of gold ions and phenylalanine, the oxidized products and their effect of sensing features are explored.

The health effects of ambient air particulate matter with a diameter of ≤2.5 μm (PM

Objective(s): We investigated whether NOS3-c.894G>T transversion (rs1799983), which causes the substitution of glutamate with aspartate (E298D) in the oxygenase domain of endothelial nitric oxide synthase (eNOS), is associated with susceptibility to metabolic syndrome (MetS) risk in Iranian-Azerbaijanis. Materials and Methods: The frequencies of the alleles and genotypes were compared in the 300 cases and 300 controls using PCR-RFLP assay. Also, higher-order MetS interaction with the genotypes, gender, age, and body mass index (BMI) was evaluated by classification and regression tree (CART) analysis. In silico analysis was done to introduce a hypothesis describing the molecular effects of NOS3-c.894G>T. Results: The T allele (OR:1.46; CI:1.054-2.04; P=0.02), GT genotype (OR:1.44; CI:1.02-2.03; P=0.03), and dominant model (TT+GT vs GG, OR:1.48; CI:1.06-2.06; P=0.01) were found to be associated with increased risk of MetS. In the male subpopulation TT genotype (OR:7.19; CI:1.53-33.70; P=0.01) was discovered to be associated with increased odds of MetS. CART analysis showed that NOS3-c.894G>T genotypes and BMI significantly contribute to modulating MetS risk. Furthermore, in silico investigation revealed that c.894G>T may alter eNOS function through affecting interactions of its oxygenase domain with proteins such as B2R, b-actin, CALM1, CAV1, GIT1, HSP90AA1, NOSIP, and NOSTRIN. Conclusion: We showed that NOS3-c.894G>T was associated with an increased risk of MetS in Iranian-Azerbaijanis, and BMI modulates the effects of NOS3-c.894G>T genotypes on MetS risk. Also, in silico analysis found that NOS3-c.894G>T may affect the interaction of the eNOS oxygenase domain with its several functional partners.

The published version of this article, unfortunately, contains error in the affiliation. The authors express their sincere apology and corrected the affiliations in this article.

A DNA-silver nanocluster with two distinct emissions is devised, in which this unique modality has been exploited to develop a novel nanosensor for transgenic DNA detection. TEM and fluorescence analysis revealed the formation of Ag nanoclusters with a size of around 2 nm, which exhibit dual-emissions at 550 nm (green) and 630 nm (red). Moreover, in the presence of the target sequence (CaMV 35S promoter) from the transgenic plant, the nanoclusters showed an enhancement in the green emission and a reduction in the red emission. This property provided a ratiometric-sensing platform which lacks unavoidable noises. The ratio of green to red fluorescence emission (G/R) of the nanoclusters exhibited a linear relation with the target concentration in the range 10 to 1000 nM. However, the control DNA did not affect this ratio, which clearly confirmed the selective response of the designed nanosensor. This sensing platform had a detection limit of 1.5 nM and identified the DNA of transgenic soybeans within a short time. The mechanistic evaluation of the nanoclusters further revealed the role of protonated cytosine bases in the dual emission behavior. Finally, unique features of the designed nanosensor may improve the current approaches for the development and manufacturing of GMO detection tools.

Methylation of DNA at carbon 5 of cytosines is the most common epigenetic modification of human genome. Due to its critical role in many normal cell processes such as growth and development, any aberrant methylation pattern in a particular locus may lead to abnormal functions and diseases such as cancer. Development of methods to detect methylation state of DNA which may eliminate labor-intensive chemical or enzymatic treatments has received considerable attention in recent years. Herein, we report a DNA methylation detection procedure based on fluorescence turn-on strategy. Target sequence was selected from Sept9 promoter region that has been reported as one of the most frequently methylated sites in colorectal cancer. Probe DNA was designed to be complementary to this sequence with an additional six cytosines in the middle to form an internal loop to host silver nanoclusters. The fluorescence intensity of the synthesized silver nanoclusters with the duplexes of probe-non-methylated target was significantly different from that of probe-methylated target. The fluorescence enhanced with increasing the methylated DNA concentration with a linear relation in the range of 1.0 × 10−8 M to 5.0 × 10−7 M with the detection limit of 8.2 × 10−9 M, and quenched with non-methylated ones. The method was very specific in the presence of non-complementary sequences with maximum similarity of 40%. Circular dichroism spectra indicated that silver ions significantly affected the structure of methylated and non-methylated DNA into different extents which could further influence the nanocluster fluorescence. Finally, a method was introduced to meet the concerns in the applicability of the proposed method in real situation.

Different bioinformatic methods apply various approaches to predict how much the effect of a SNP could be deleterious and therefore their results may differ significantly. However, variation studies often need to consider an integrated prediction result to analyze the effect of SNPs. To address this problem, we used an algorithm to map ordinal predictions to a numeral space and averaging them, and based on it we developed the ISNPranker web-tool ( http://isnpranker.semilab.ir/ ). It takes heterogonous outputs of different predictors and generates integrated numerical predictions and ranks SNPs based on them. Afterward, we used ISNPranker to identify the most deleterious coding SNPs (cSNPs) of the human aryl hydrocarbon receptor (AHR) gene. AHR is a ligand-activated transcription factor that governs many molecular and cellular mechanisms and cSNPs may affect its structure, interactions, and function. Forty validated cSNPs of AHR were initially analyzed using 16 publicly available SNP analyzers and the results were introduced to the ISNPranker and integrated predictions were obtained. The cSNPs were ranked in 34 levels of danger and rs200257782 in the ARNT dimerization domain (ADD121-289) of AHR was identified as the most deleterious cSNP. The rs148360742, which affect ADD40-79 and Hsp90 binding domain (HBD27-79) was in the second rank and the third and fourth ranks were occupied by ADD121-289-located variations rs571123681 and rs141667112 respectively. In conclusion, we introduced ISNPranker, which is a web-tool for integrative ranking of SNPs, and we showed that AHR structure and function may be highly sensitive to the cSNPs in the ARNT dimerization domain.

Silver ions can influence DNA structure. The extent of this structural perturbation is different in methylated and non-methylated DNA. Here, we explored the interaction of eight convenient DNA interacting molecules with methylated and non-methylated short GC rich oligonucleotides in the presence and absence of silver ions. Acridine orange, DAPI, Doxorubicin, Ethidium bromide, Hoechst 33342, Methylene blue, PicoGreen, and Propidium iodide are tested for their ability to distinguish methylated and non-methylated DNA. Among them, Ethidium bromide, Methylene blue, and PicoGreen were able to discriminate between methylated and non-methylated DNA, while DAPI and Hoechst 33342 were only able to discriminate with the aid of silver ions. A detection method is proposed using Ethidium bromide in which the silver-treated sample of DNA exposed different fluorescence intensity from the untreated one on the base of its methylation state. This phenomenon was sequence-dependent and could provide a sensing platform with a detection limit of about 40 nM.

DNA methylation, histone modification, and ncRNA function are the main epigenetic mechanisms involved in the regulation of gene expression and there are single nucleotide polymorphisms (SNPs) that may affect them. Although these SNPs have an important role in connecting genetic and epigenetic levels of gene regulation, they have not been classified in an independent category until now. Therefore, we introduce the EpiPol concept, which abbreviates the epigenetic affecting polymorphism and describes those variations in the regulatory sequences of a gene, which may affect epigenetic regulations of its expression. Aryl hydrocarbon receptor (AHR) is a multifunctional regulator in cell physiology and xenobiotics metabolism and its altered regulation have been shown to result in adverse developmental and physiological outcomes. Recently, the therapeutic potential of modulating the methylation status of the AHR promoter has been discussed. Using Bioinformatics approaches, we aimed to identify the polymorphisms in upstream regulatory sequences of AHR, which may affect the epigenetic regulation of it through the introduction or removal of CpG dinucleotides that act as possible targets for DNA methylation. The 3000 bp upstream regulatory sequences of AHR, −2700 to +300 relative to the ATG codon, were obtained from NCBI. The CpG-island identified and all 105 SNPs located in it were retrieved from dbSNP. After that, 45 SNPs that cause the introduction or removal of CpGs were identified as candidate EpiPols of AHR. Then, the methylation status of these EpiPols analyzed using Bioinformatics servers, and finally, 13 SNPs were reported as predicted methylation-affecting EpiPols of the human AHR gene.

Citrus Tristeza Virus (CTV) was detected by targeting the virus capsid protein, CP25, through a competitive fluorescence anisotropic immunoassay. In this assay, instead of using chromophore labeled tracers, a simple approach in which the target antigen serves both as the main target and tracer was developed. For this, CP25 was expressed in E.coli and the purified recombinant protein was manipulated for copper nanocluster synthesis. The resultant CP25/CuNCs optically showed quantum dot-like behavior and emitted light in a range of 535–715 nm. The CP25/CuNCs could also interact with the anti-CTV antibody and showed polarized emission. In this assay, the CP25 protein competes with the fluorescent CP25/CuNCs used as a tracer for immune-complex formation with the anti-CTV antibody. The results showed that the FA values decreased linearly from 400 pg/mL to 25 ng/mL with an increase in CP25 protein levels and the limit of detection (LOD) was 220 pg/mL. The procedure of this assay can be useful for the detection of low molecular weight proteins or peptides in general, due to the availability of various kinds of metal nanoclusters and synthesis protocols.

Protein misfolding and aggregation into amyloid structures is linked with a number of pathophysiological disorders. In the past decade, significant progresses have been made in the drug discovery strategies against toxic aggregates. Although lack of specificity and high sensitivity for in vitro screening system still seen. Here we demonstrate a new targeting probe based on FF diphenylalanine peptide -protected gold nanoclusters (FF AuNCs). Diphenylalanine peptide has previously been shown to self-assemble into well-ordered fiber like the fibers that are observed in amyloid aggregates. We used of the self-assembly properties along with the ability of FF dipeptide in reduction of gold ions for synthesis of novel Au nanoclusters. We used FF AuNCs for monitoring of effectiveness of anti-amyloid drugs. Fluorescence was considerably diminished when drugs at different concentrations added, due to destruction of the amyloid fibers. Furthermore, the analysis of several components demonstrates significant selectivity against the amyloid disrupting molecules. Prepared FF AuNCs will gain possible strategy for in vitro screening of amyloid disrupting molecules.

Determining methylation state of a particular DNA sequence is an essential task in many epigenetic investigations. Here a facile method based on silver nanocluster (AgNCs) fluorescence enhancement is presented. Target sequences were selected from Sept9 promoter region that its hypermethylation is demonstrated as a reliable biomarker of colorectal cancer. Probe DNA was complementary to a 25 nucleotide of the target region and possessed twelve additional cytosines in the middle to grant the formation of AgNCs. After probe strands were hybridized with methylated and non-methylated targets separately, AgNCs were synthesized, and their fluorescence intensities were recorded. Fluorescence intensity enhanced when the target strands were methylated and quenched when they were non-methylated. The Linear range of fluorescence enhancement was from 1.0 × 10-7 M to 5.0 × 10-7 M with the detection limit of 7.6 × 10-8 M. Sensor specificity was checked with non-complementary strands with the maximum similarity of 40%. Further experiments explored various characteristics of methylated and non-methylated DNAs carrying AgNC and indicated that structure of methylated and non-methylated DNAs was affected differently by silver ions that could then influence AgNC fluorescence. This effect was strongly sequence-dependent, and either fluorescence enhancement or quenching was observed with two different sequences.