A cyanobiphenyl-based fluorescent ''lighting-up'' sensor for highly selective and sensitive recognition of Al3+: Theoretical, practical and bioimaging studies.

The recognition of toxic Al3+ in foods and biosystems has of great interest to researchers. Herein, a novel cyanobiphenyl-based chemosensor CATH (E)-N'-((4'-cyano-4-hydroxy-[1,1'-biphenyl]-3-yl)methylene)thiophene-2-carbohydrazide was fabricated and shown to recognize Al3+ in HEPES buffer:EtOH (90:10, v:v, pH = 7.4) by ''lighting-up'' fluorescence sensing. The CATH evidenced high sensitivity (LOD = 13.1 nM) and excellent selectivity to Al3+ over competing cations. The Job's plot, TOF-MS and theoretical computation studies were performed to probe the binding mechanism of Al3+ to CATH. Additionally; CATH was successfully utilized to practical applications and employed to recover of Al3+ from different food samples. More importantly, it was employed to intracellular Al3+ detection in living cells including THLE2 and HepG2.

Resveratrol and regular exercise may attenuate hypertension-induced cardiac dysfunction through modulation of cellular stress responses.

AIMS: Hypertension is one of the major causes of cardiac damage. In this study, the effects of resveratrol supplementation and regular exercise on hypertension-induced cellular stress responses of myocardium were compared. MAIN METHODS: Hypertension was induced in male Wistar rats by deoxycorticosterone-acetate + salt administration for 12 weeks. Resveratrol and regular exercise were applied for the last six weeks. In addition to biochemical and molecular examinations, isoprenaline, phenylephrine and, acetylcholine-mediated contractions and sinus rate were recorded in the isolated cardiac tissues. KEY FINDINGS: Resveratrol and regular exercise reduced systolic blood pressure in hypertensive rats. The altered adrenergic and cholinergic responses of the right atrium and left papillary muscles in hypertension were separately improved by resveratrol and regular exercise. Resveratrol and regular exercise decreased plasma and cardiac total antioxidant capacity and, augmented the expression of antioxidant genes in hypertensive rats. While regular exercise restored the increase in p-PERK expression associated with endoplasmic reticulum stress and decrease in mitophagic marker PINK1 expression, resveratrol only ameliorated PINK1 expression in hypertensive rats. Resveratrol and exercise training suppressed hypertension-induced NLRP3 inflammasome activation by reversing the increase in NLRP3, p-NF-κB expression and the mature-IL-1ß/pro-IL-1ß and cleaved-caspase-1/pro-caspase-1 ratio. Resveratrol and exercise enhanced mRNA expression of caspase-3, bax, and bcl-2 involved in the apoptotic pathway, but attenuated phosphorylation of stress-related mitogenic proteins p38 and JNK induced by hypertension. SIGNIFICANCE: Our study demonstrated the protective effect of resveratrol and exercise on hypertension-induced cardiac dysfunction by modulating cellular stress responses including oxidative stress, ER stress, mitophagy, NLRP3 inflammasome-mediated inflammation, and mitogenic activation.

Lactobacillus plantarum improves lipogenesis and IRS-1/AKT/eNOS signalling pathway in the liver of high-fructose-fed rats.

In the present study, we investigated the influence of Lactobacillus plantarum and Lactobacillus helveticus supplementation on lipogenesis, insulin signalling and glucose transporters in liver of high-fructose-fed rats. Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Lactobacillus plantarum and L. helveticus supplementations were performed by gastric gavage once a day during final 6 weeks. Dietary high-fructose increased hepatic weight, lipid accumulation and FASN expression as well as caused a significant reduction in IRS-1 expression, pAKT/total AKT and peNOS/total eNOS ratios, but an elevation in GLUT2 and GLUT5 mRNAs in the liver. Lactobacillus plantarum supplementation decreased hepatic weight, triglyceride content and FASN expression as well as improved IRS-1/AKT/eNOS pathway and GLUT2 expression in the liver of high-fructose-fed rats. However, L. helveticus supplementation exerted a restoring effect on lipid accumulation by decreasing FASN expression, and regulating effect on IRS-1 and GLUT2 expressions.

Masseter muscle and gingival tissue inflammatory response following treatment with high-fructose corn syrup in rats: Anti-inflammatory and antioxidant effects of kefir.

The aim of the study was to evaluate whether high-fructose corn syrup (HFCS) intake (20% beverages) impacts antioxidative structures and inflammation in the gingival tissue and masseter muscle of rats. Kefir was tested for its potential utility on changes induced by HFCS. Animals were randomly divided into four groups as control, kefir, HFCS, and HFCS plus kefir. HFCS was given as 20% solutions in drinking water while kefir supplementations were given by gastric gavage for 8 weeks. It has been clearly determined that the HFCS diet increased expressions of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α proinflammatory structures via lymphocyte infiltration by suppressing antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase in both tissues. Kefir improved these undesirable changes in rats fed with HFCS. The results of this current study, the first investigation to examine the effects of kefir on masseter muscle and gingival tissue, may provide new access to the restorative effects of kefir consumption on oral health disorders caused by high fructose in the diet. PRACTICAL APPLICATIONS: In this study, at an early age, the effects of kefir on improving inflammation via antioxidation in the masseter muscle and gingival tissue were investigated for the first time. We showed that kefir feeding ameliorates lymphocyte infiltration on the high-fructose corn syrup (HFCS)-induced masseter muscle and gingival tissue inflammation in rats. The mRNA expressions of inflammatory parameters measured in the study were supported by protein measurements via ELISA or immunohistochemistry. In the present study, kefir may play an important role in the antioxidation and inflammation process on the masseter muscle and gingival tissue against HFCS.

Potential mechanistic pathways underlying intestinal and hepatic effects of kefir in high-fructose-fed rats.

Excess intake of fructose may contribute to the high prevalence of metabolic disorder. In this study, we investigated the effects of kefir supplementation on the intestine-liver-adipose tissue axis in metabolic disorder induced by high-fructose diet in rats to describe mechanistic action and potential therapeutic value of kefir. Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Kefir was administrated by gastric gavage once a day during the final six weeks. Kefir supplementation improved metabolic parameters, including plasma triglyceride and insulin levels; hepatic weight, triglyceride content and fatty degeneration; omental fat mass in fructose-fed rats. Kefir supplementation decreased the ratio of Firmicutes/Bacteroidetes in feces, as well as necrotic degeneration, expression levels of nuclear factor-kappa B (NF-κB), and inducible nitric oxide synthase (iNOS), but increased expression of tight-junction proteins occludin and claudin-1, in the ileum of the fructose-fed rats. Kefir treatment also reduced the mRNA levels of key lipogenic genes sterol regulatory element-binding protein (SREBP-1c) and fatty acid synthase (FASN) together with a decline in expression of tumor necrosis factor-alpha (TNF-α), NF-κB, and glycosylated glycoprotein (CD68) in the liver. Moreover, kefir treatment improved insulin signaling at the level of insulin receptor substrate 1 (IRS-1) and phospho-endothelial nitric oxide synthase (peNOS) as well as fructose transporters (GLUT2 and GLUT5) in the liver, but not in the adipose tissue, of high-fructose-fed rats. Consequently, kefir supplementation suppresses hepatic lipogenesis and inflammatory status, but promotes insulin signaling, in association with a change of the fecal microbiota and attenuation of the intestinal permeability factors in high-fructose-fed rats. Thus, we propose that kefir has favorable effects on the hepatic and intestinal irregularities induced by fructose overconsumption.

A novel fluorescent probe based on isocoumarin for Hg2+ and Fe3+ ions and its application in live-cell imaging.

Synthesis of the 2-amino-4-phenyl-6- (isocoumarin-3-yl) -3-cyanopyridine (APICP) containing both isocoumarin and pyridine ring in its structure was carried out, and this compound was characterized by ATR-FTIR, 1H NMR, and 13C NMR spectral techniques. A fluorescence sensor determining Hg2+ and Fe3+ ions in DMSO/HEPES buffer solution (9/1 v/v, 5 µM, pH 7.0) was developed using the synthesized compound, and the detection limits of the sensor with exquisite selectivity were calculated as 8.12 nM and 5.51 nM for Hg2+ and Fe3+ ions, respectively. Jobs plot method was used to determine the stoichiometry of APICP-Hg2+/Fe3+ complexes as 2:1 and FT-IR and ESI-MS methods confirmed the results. Besides, cell growth inhibitory potentials of the sensor over HepG2 cells and in vivo fluorescent cell imaging experiments were conducted. Findings revealed the relatively low cytotoxic effects of the synthesized sensor (IC50: 0.541 ±â€¯0.039 mM), and it could be utilized as an intracellular imaging agent for the determination of Fe3+ and Hg2+ ions in biological systems.

Oxidative DNA Damage-Mediated Genomic Heterogeneity Is Regulated by NKX3.1 in Prostate Cancer.

The 8-hydroxy-2'-deoxyguanosine (8-OHdG) damages are base damages induced by reactive oxygen species. We aimed to investigate the role of Androgen Receptor and NKX3.1 in 8-OHdG formation and repair activation by quantitating the DNA damage using Aklides.NUK system. The data demonstrated that the loss of NKX3.1 resulted in increased oxidative DNA damage and its overexpression contributes to the removal of menadione-induced 8-OHdG damage even under oxidative stress conditions. Moreover, 8-oxoguanine DNA glycosylase-1 (OGG1) expression level positively correlates to NKX3.1 expression. Also in this study, first time a reliable cell-based quantitation method for 8-OHdG damages is reported and used for data collection.

Modulation of Renal Insulin Signaling Pathway and Antioxidant Enzymes with Streptozotocin-Induced Diabetes: Effects of Resveratrol.

Background and objectives: Diabetes mellitus is a disease of insulin deficiency or its inability of usage by the target tissues leading to impairment of carbohydrate, lipid, and protein metabolisms. Resveratrol, having robust anti-inflammatory and anti-oxidant properties, has a high potential to treat or prevent the pathogenesis of diseases. This study was conducted to reveal the relationship between diabetes-induced oxidative stress and tissue inflammation with changes in main enzymatic antioxidants (cat, sod, gpx, and gst) and the components of the insulin signaling pathway (insulin Rß, irs-1, pi3k, akt, mtor) in kidney tissues. Additionally, the effects of resveratrol on these parameters were evaluated. Materials and Methods: Male Wistar rats were randomly divided into four groups; (1) control/vehicle; (2) control/20 mg/kg resveratrol; (3) diabetic/vehicle; (4) diabetic/20 mg/kg resveratrol. Gene and protein expressions of antioxidant enzymes and insulin signaling elements were evaluated in renal tissues. Results: Downregulation of antioxidant enzymes' gene expression in the kidney tissues of diabetic rats was demonstrated and this situation was devoted partially to the reduced gene expression of nfκb. Moreover, the components of renal insulin signaling elements were upregulated at both gene and protein expression levels in diabetic rats, and resveratrol treatment decreased this sensitization towards the control state. Conclusion: Resveratrol partially improved diabetes-induced renal oxidative stress and inflammation due to healing action on renal antioxidant enzymes and insulin signaling pathway components.

Automated Cell-Based Quantitation of 8-OHdG Damage.

Detection of 8-OHdG-base damage has been a big challenge for decades, though different analytical methods are developed. The recent approaches that are used for quantitating either the total amount of base damage or the amount of base damage per cell from different sources of samples are not automated. We have developed a method for automated damage detection from a single cell and applied it to 8-OHdG quantitation.