Genetic variation in salt taste receptors impact salt intake and blood pressure.

So far, few studies have examined the effect of salt taste receptors genetic variation on dietary intake in the Iranian population. We aimed to evaluate associations between single nucleotide polymorphisms (SNPs) in salt taste receptors' genes with dietary salt intake and blood pressure. A cross-sectional study was carried out among 116 randomly selected healthy adults aged ≥ 18 in Isfahan, Iran. Participants underwent sodium intake determination by 24-h urine collection, as well as dietary assessment by semi-quantitative food frequency questionnaire and blood pressure measurement. Whole blood was collected to extract DNA and genotype of SNP rs239345 in SCNN1B and rs224534, rs4790151 and rs8065080 in TRPV1 gene. Sodium consumption and diastolic blood pressure were significantly higher in carriers of the A-allele in rs239345 compared to subjects with the TT genotype (4808.4 ± 824.4 mg/day vs. 4043.5 ± 989.3 mg/day; P = 0.004) and 83.6 ± 8.5 mmHg vs. 77.3 ± 7.3 mmHg; P = 0.011), respectively. The level of sodium intake was lower in the TT genotype of TRPV1 (rs224534) than the CC genotype (3767.0 ± 713.7 mg/day vs. 4633.3 ± 793.5 mg/day; P = 0.012). We could not find any association between genotypes of all SNPs with systolic blood pressure as well as genotypes of rs224534, rs4790151 and rs8065080 with diastolic blood pressure. Genetic variations can relate with salt intake and consequently may associate with hypertension and finally cardiovascular disease risk in the Iranian population.

Anti-inflammatory and -apoptotic effects of a long-term herbal extract treatment on DSS-induced colitis in mice fed with high AGEs-fat diet.

BACKGROUND: Obesity is associated with many comorbidities including inflammatory bowel disease (IBD). We investigated prophylactic effects of an herbal extract (HE) on the DSS-induced colitis mice challenged with high AGEs-fat diet 60% (HFD). METHODS: Six-week-old C57BL/6 male mice were fed with either HFD (8 groups, 6 mice in each group), or normal diet (ND) (8 groups, 6 mice in each group). After 6 weeks, animals received HE (combination of turmeric, ginger, boswellia and cat's claw extract) for 7 weeks in three doses (high dose (0.6 mg/g); low dose (0.15 mg/g) and mid dose (0.3 mg/g)). Next, mice were subjected to 2.5% DSS in drinking water. Control mice received ND and instead of HE and DSS they received distilled water. Obesity index markers were determined, H&E staining and TUNEL assay evaluated apoptosis. Colonic expressions of IL-6, RAGE, AGER1, Sirt1, Bax, Bcl2, ZO-1 and P53 were determined. RESULTS: HE ameliorated colitis in HFD mice by reducing colonic myeloperoxidase activity (by 2.3-fold), macrophage accumulation (by 2.6-fold) and mRNA expression of IL-6 (by 2.3-fold) in HFD mice. Moreover, HE restored ZO-1 (by 2.7-fold), prevented apoptosis and maintained immune homeostasis. HE reduced activation of NF-κB protein (by 1.3-fold) through decreasing RAGE (by 1.93-fold) and up-regulation of Sirt1 (by 7.71-fold) and prevented down-regulation of DDOST (by 6.6-fold) in HFD mice. CONCLUSIONS: HE ameliorated colitis in prophylactic in HFD mice and it was, at least partly, due to the restoration of the gut integrity, suppression of inflammation and apoptosis via modulation of colonic Sirt1, RAGE and DDOST signaling.

Receptor for Advanced Glycation End Products Acts as a Fuel to Colorectal Cancer Development.

Receptor for advanced glycation end-products (RAGE) is a multiligand binding and single-pass transmembrane protein taken in diverse chronic inflammatory conditions. RAGE behaves as a pattern recognition receptor, which binds and is engaged in the cellular response to a variety of damage-associated molecular pattern molecules, as well as HMGB1, S100 proteins, and AGEs (advanced glycation end-products). The RAGE activation turns out to a formation of numerous intracellular signaling mechanisms, resulting in the progression and prolongation of colorectal carcinoma (CRC). The RAGE expression correlates well with the survival of colon cancer cells. RAGE is involved in the tumorigenesis, which increases and develops well in the stressed tumor microenvironment. In this review, we summarized downstream signaling cascade activated by the multiligand activation of RAGE, as well as RAGE ligands and their sources, clinical studies, and tumor markers related to RAGE particularly in the inflammatory tumor microenvironment in CRC. Furthermore, the role of RAGE signaling pathway in CRC patients with diabetic mellitus is investigated. RAGE has been reported to drive assorted signaling pathways, including activator protein 1, nuclear factor-κB, signal transducer and activator of transcription 3, SMAD family member 4 (Smad4), mitogen-activated protein kinases, mammalian target of rapamycin, phosphoinositide 3-kinases, reticular activating system, Wnt/ß-catenin pathway, and Glycogen synthase kinase 3ß, and even microRNAs.

Impact of sodium arsenite on chromosomal aberrations with respect to polymorphisms of detoxification and DNA repair genes.

Arsenic compounds can increase production of reactive oxygen species. Reactive oxygen species can induce double-strand breaks in DNA, which is a cause of chromosome aberrations (CAs). This study was conducted to determine the association between arsenic exposure and polymorphisms of genes involved in detoxification (glutathione S-transferase T1 [GSTT1], glutathione S-transferase M1 [GSTM1], glutathione S-transferase O2 [GSTO2], catalase [CAT], and NAD(P)H quinone oxidoreductase1 [NQO1]) as well as nonhomologous end joining DNA repair genes (XRCC4, XRCC5, and XRCC6) with induction of chromosomal aberrations. The participants consisted of 123 healthy males who were genotyped using polymerase chain reaction-based methods. Primary cultures of whole blood were treated with sodium arsenite (NaAsO(2); iAs(III); at final concentration 1 µmol/L), mitomycin C (at final concentration 60 ηg/mL; as positive control), or untreated. For each culture, mitotic index (MI), chromatid breaks (CBs), CAs, and total percentage of aberrant cells were determined. The levels of CB and percentage of aberrant cells were significantly higher in the TT genotype of CAT (C-262T polymorphism) than the CC genotype. The CB value in samples with GSTM1 active genotype was significantly higher than the null genotype. The MI in samples with TT genotype of NQO1 (C609T polymorphism) was significantly higher than MI in samples having CC and CT genotypes. There was no association between MI, CB, CA, and percentage of aberrant cells and polymorphisms of XRCC4, XRCC5, and XRCC6.