Aryl hydrocarbon receptor expression in serum, peripheral blood mononuclear cells, and skin lesions of patients with atopic dermatitis and its correlation with disease severity.

BACKGROUND: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, which is critically involved in the pathogenesis of a variety of skin diseases. The aim of this study was to detect AhR and its downstream regulators including cytochrome P450 (CYP1A1), AhR nuclear translocation (ARNT), and aryl hydrocarbon receptor repressor (AhRR) in serum, peripheral blood mononuclear cells (PBMCs), and skin lesions in patients with atopic dermatitis (AD). METHODS: Twenty-nine AD patients defined according to the criteria of Hanifin and Rajka and Chinese criteria of AD were included. Subjects without allergic and chronic diseases were recruited as controls. Patients and controls were selected from the dermatology outpatient clinic of Peking University People's Hospital from August 1 to December 31 in 2018. Enzyme-linked immunosorbent assay was performed to detect serum AhR level. The mRNA of AhR, AhRR, ARNT, and CYP1A1 in PBMCs were measured by real-time quantitative polymerase chain reaction. AhR expression in skin lesions was measured by immunohistochemistry. RESULTS: AhR was significantly higher expressed in serum (41.26 ±â€Š4.52 vs. 33.73 ±â€Š2.49 pmol/L, t = 6.507, P < 0.001) and skin lesions (0.191 ±â€Š0.041 vs. 0.087 ±â€Š0.017, t = 10.036, P < 0.001) of AD patients compared with those of controls. The mRNA levels of AhR (1.572 ±â€Š0.392 vs. 1.000 ±â€Š0.173, t = 6.819, P < 0.001), AhRR (2.402 ±â€Š1.716 vs. 1.000 ±â€Š0.788, t = 3.722, P < 0.001), CYP1A1 (2.258 ±â€Š1.598 vs. 1.000 ±â€Š0.796, t = 3.400, P = 0.002) in PBMCs of AD patients were higher compared with those of controls. The difference in mRNA levels of ARNT was not statistically significant between the patients and controls (1.383 ±â€Š0.842 vs. 1.000 ±â€Š0.586, t = 1.653, P = 0.105). AhR mRNA levels in PBMCs positively correlated with eczema area and severity index score and serum interleukin-6 levels. CONCLUSION: AhR and its downstream regulators were highly expressed in serum, PBMCs, and skin of AD patients, which might contribute to the pathogenesis of AD.

The Mediterranean diet reduces the genetic risk of chromosome 9p21 for myocardial infarction in an Asian population community cohort.

The interaction of genetic susceptibility and dietary habits in cardiovascular disease (CVD) remains undetermined. The purpose of this study was to investigate whether a Mediterranean dietary style modified the genetic risk of developing CVD in a Chinese cohort. A total of 2098 subjects with dietary information from a Chinese community cohort (CVDFACTS) were enrolled. Candidate genes, including SNP markers rs1333049 (CDKN2B, 9p21.3), rs17465637 (MIA3, 1q41) and rs501120 (CXCL12, 10q11.21), were genotyped to analyze the association with future CVD. The impact of dietary pattern was also analyzed according to adherence to the diet using the Mediterranean Diet Score (MDS). After an average follow-up of 7.8 years, only the C risk allele of rs1333049 at chromosome 9p21.3 was associated with a higher risk of MI with either an additive [HR = 1.78, 95% CI:1.23-2.5] or a recessive model [HR = 2.40, 95% CI: 1.42-4.04], and the CC genotype had a higher risk of developing MI (p = 0.009, log-rank test). There was no significant difference in the association of the lipid profile with future CV outcomes among the MDS tertiles. However, the high MI risk of the CC genotype in individuals consuming a less healthy diet (MDS1) (HR: 6.39, 95% CI: 1.74-23.43) significantly decreased to 2.38 (95% CI: 0.57-10.04) in individuals consuming a healthier diet (MDS3), indicating that a healthier dietary pattern (higher MDS) modified the risk of developing MI in carriers of variants in CDKN2B. In conclusion, genetic variants of CDKN2B at 9p21 were significantly associated with future MI risk in a Chinese cohort, and the genetic risk of MI could be modified by a healthier diet.

GWAS implicated risk variants in different genes contribute additively to increase the risk of coronary artery disease (CAD) in the Pakistani subjects.

BACKGROUND: Coronary artery disease (CAD) remains the single most important cause of mortality worldwide. Many candidate and GWAS genetic variants have been identified in the recent years. In the current study, we selected six SNPs from various genes that have originally been identified in GWAS studies and examined the association of SNPs individually and as a genetic risk score (GRS) with CAD and blood lipid levels in the Pakistani subjects. METHODS: Six hundred twenty-four (404 cases and 219 controls) subjects were genotyped for variants rs10757274 in CDKN2A gene, rs17465637 in MIA3 gene, rs7025486 in DAB2IP gene, rs17228212 in SMAD3 gene, rs981887 in MRAS gene and rs1746048 in CXCL12 gene, by TaqMan and KASPar allele discrimination techniques. Serum lipid parameters were measured using commercially available kits. Statistical analyses were done using SPSS version 22. RESULTS: Individually, the single SNPs were not associated with CAD (p < 0.05). However, the combined GRS of 6 SNPs was significantly higher in cases than controls (4.89 ± 0.11 vs 4.58 ± 0.08, p = 0.024). Among blood lipids, GRS showed significant positive association with serum triglycerides levels (p = 0.022). CONCLUSION: The GRS was quantitatively associated with CAD risk and showed association with serum triglycerides levels, suggesting that the mechanism of these variants is likely to be in part at least through creating an atherogenic lipid profile in subjects carrying high numbers of risk alleles.

A Single Meal Containing Raw, Crushed Garlic Influences Expression of Immunity- and Cancer-Related Genes in Whole Blood of Humans.

BACKGROUND: Preclinical and epidemiologic studies suggest that garlic intake is inversely associated with the progression of cancer and cardiovascular disease. OBJECTIVE: We designed a study to probe the mechanisms of garlic action in humans. METHODS: We conducted a randomized crossover feeding trial in which 17 volunteers consumed a garlic-containing meal (100 g white bread, 15 g butter, and 5 g raw, crushed garlic) or a garlic-free control meal (100 g white bread and 15 g butter) after 10 d of consuming a controlled, garlic-free diet. Blood was collected before and 3 h after test meal consumption for gene expression analysis in whole blood. Illumina BeadArray was used to screen for genes of interest, followed by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) on selected genes. To augment human study findings, Mono Mac 6 cells were treated with a purified garlic extract (0.5 µL/mL), and mRNA was measured by qRT-PCR at 0, 3, 6, and 24 h. RESULTS: The following 7 genes were found to be upregulated by garlic intake: aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT), hypoxia-inducible factor 1α (HIF1A), proto-oncogene c-Jun (JUN), nuclear factor of activated T cells (NFAT) activating protein with immunoreceptor tyrosine-based activation motif 1 (NFAM1), oncostatin M (OSM), and V-rel avian reticuloendotheliosis viral oncogene homolog (REL). Fold-increases in mRNA transcripts ranged from 1.6 (HIF1A) to 3.0 (NFAM1) (P < 0.05). The mRNA levels of 5 of the 7 genes that were upregulated in the human trial were also upregulated in cell culture at 3 and 6 h: AHR, HIF1A, JUN, OSM, and REL. Fold-increases in mRNA transcripts in cell culture ranged from 1.7 (HIF1A) to 12.1 (JUN) (P < 0.01). OSM protein was measured by ELISA and was significantly higher than the control at 3, 6, and 24 h (24 h: 19.5 ± 1.4 and 74.8 ± 1.4 pg/mL for control and garlic, respectively). OSM is a pleiotropic cytokine that inhibits several tumor cell lines in culture. CONCLUSION: These data indicate that the bioactivity of garlic is multifaceted and includes activation of genes related to immunity, apoptosis, and xenobiotic metabolism in humans and Mono Mac 6 cells. This trial is registered at clinicaltrials.gov as NCT01293591.

Immune-relevant and new xenobiotic molecular biomarkers to assess anthropogenic stress in seals.

Harbour seals as top predators and indicators for ecosystem health are exposed to increasing pressure caused by anthropogenic activities in their marine environment. After their lactation period of about 24 days pups are weaned and left to hunt on their own. Little is known about the development of their immune system and a better understanding of anthropogenic impacts on the general health and immune system of harbour seal pups is needed. mRNA transcription of six immuno-relevant biomarkers was analysed in 13 abandoned harbour seal pups from the North Sea, fostered at the Seal Centre Friedrichskoog, Germany. RNAlater blood samples were taken at admission, day 22 and before release and analysed using RT-qPCR. Significant differences in HSP70, cytokine IL-2 and xenobiotic biomarkers AHR, ARNT and PPARα transcription were found between admission, during rehabilitation and before release. Highest levels at admission may result from dehydration, handling, transport and contaminant exposure via lactation. The significant decrease is linked to health improvement, feeding and adaptation. The increase before release is suspected to be due to infection pressure and contaminant exposure from feeding on fish. Molecular biomarkers are a sensitive tool to evaluate health and pollutant exposure and useful to serve as early warning indicators, monitoring and case-by-case tool for marine mammals in human care and the wild.