Abstract

Background

Hypertriglyceridemia, insulin resistance and hyperglycemia are risk factors for atherosclerosis in type 2 diabetes. Angiopoietin-like protein 8 (ANGPTL8) is a newly identified liver-derived hormone related to these risk factors. Hence, we aimed to explore the correlations between serum levels of ANGPTL8 and subclinical atherosclerosis in type 2 diabetes.

Methods

We measured serum ANGPTL8, blood lipids, blood glucose, common carotid artery Intima-Media Thickness (c-IMT) and calculated homeostasis model assessment of insulin resistance in (1) control subjects (n?=?100), (2) type 2 diabetic patients without subclinical atherosclerosis (n?=?100), and (3) type 2 diabetic patients with subclinical atherosclerosis (n?=?100).

Results

Serum levels of ANGPTL8 and triglyceride (TG) were significantly increased in type 2 diabetic patients with subclinical atherosclerosis as compared with type 2 diabetic patients without subclinical atherosclerosis and control subjects (P?<?0.001). ANGPTL8 was positively associated with age, TG, diabetes duration, and c-IMT in type 2 diabetes. Logistic regression analysis revealed that ANGPTL8 had higher odds of having subclinical atherosclerosis [odds ratio (OR) 2.90, 95% confidence interval (CI) 1.48–5.70, P?=?0.002] in type 2 diabetes. Mediation analysis indicated that TG acted as a partial mediator in the relationship between ANGPTL8 and c-IMT.

Conclusions

TG partially mediates the positive relationship between ANGPTL8 and c-IMT. Our data provide the first evidence for a strong link between ANGPTL8 and subclinical atherosclerosis, suggesting ANGPTL8 to be a new biomarker for subclinical atherosclerosis in type 2 diabetes.

Keywords

ANGPTL8 Atherosclerosis Type 2 diabetes Triglyceride Insulin resistance Hyperglycemia 

Abstract

Background

The aim of this study was to analyse the effect of pomegranate juice (POM) supplementation on the levels of selected pro-inflammatory cytokines, hepcidin and markers of iron metabolism in well-trained rowers.

Method

The double-blind placebo-controlled study included 19 members of the Polish Rowing Team. The athletes were randomised into the supplemented group (n?=?10), receiving 50 ml of standardised POM daily for two months, or the placebo group (n?=?9). The subjects performed a 2000 m test on the rowing ergometer at the start of the project (baseline) and end of follow-up period. Blood samples from the antecubital vein were obtained three times during each trial: prior to the exercise, one minute after the test, and following a 24 h recovery.

Results

The study documented the beneficial effect of supplementation with pomegranate fruit juice on TAC (P?<?0.002). During the resting period, TAC level in the supplemented group was significantly higher than in the placebo group (x?±?SD, 2.49?±?0.39 vs. 1.88?±?0.45, P?<?0.05). The ergometric test conducted at baseline demonstrated a significant post-exercise increase in the concentrations of soluble transferrin receptors (P?<?0.04), iron (P?<?0.002) and IL-6 (P?<?0.02), and to a significant post-exercise decrease in TAC. A significant increase in IL-6 concentration was also observed 24 h post-exercise. The exercise test conducted at the end of the follow-up period resulted in a significant decrease in TBIC and a significant increase in UIBC (P?<?0.001), observed in both groups, both immediately post-exercise and after the resting period.

Conclusion

Supplementation with POM contributed to a significant strengthening of plasma antioxidant potential in the group of well-trained rowers, but had no effect on iron metabolism markers.

Abstract

Despite the effectiveness of renin-angiotensin blockade in retarding diabetic nephropathy progression, a considerable number of patients still develop end-stage renal disease. The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor of receptor for advanced glycation end products (RAGE), alone and in combination with valsartan, an angiotensin receptor blocker, against glomerular injury parameters in streptozotocin-induced diabetic rats. FPS-ZM1 at 1 mg/kg (i.p.), valsartan at 100 mg/kg (p.o.), and their combination were administered for 4 weeks, starting 2 months after diabetes induction in rats. Tests for kidney function, glomerular filtration barrier, and podocyte slit diaphragm integrities were performed. Combined FPS-ZM1/valsartan attenuated diabetes-induced elevations in renal levels of RAGE and phosphorylated NF-κB p65 subunit. It ameliorated glomerular injury due to diabetes by increasing glomerular nephrin and synaptopodin expressions, mitigating renal integrin-linked kinase (ILK) levels, and lowering urinary albumin, collagen type IV, and podocin excretions. FPS-ZM1 also improved renal function as demonstrated by decreasing levels of serum cystatin C. Additionally, the combination also alleviated indices of renal inflammation as revealed by decreased renal monocyte chemoattractant protein 1 (MCP-1) and chemokine (C-X-C motif) ligand 12 (CXCL12) expressions, F4/80-positive macrophages, glomerular TUNEL-positive cells, and urinary alpha-1-acid glycoprotein (AGP) levels. These findings underline the benefits of FPS-ZM1 added to valsartan in alleviating renal glomerular injury evoked by diabetes in streptozotocin rats and suggest FPS-ZM1 as a new potential adjunct to the conventional renin-angiotensin blockade.

Abstract

Triclocarban is a phenyl ether that has recently been classified as a contaminant of emerging concern. Evidence shows that triclocarban is present in human tissues, but little is known about the impact of triclocarban on the nervous system, particularly at early developmental stages. This study demonstrated that triclocarban that was used at environmentally relevant concentrations induced apoptosis in mouse embryonic neurons, inhibited sumoylation, and changed the epigenetic status, as evidenced by impaired activities of HDAC, sirtuins, and DNMT, global DNA hypomethylation, and alterations of methylation levels of bax, bcl2, Ahr, and Car genes. The use of selective antagonists and specific siRNAs, which was followed by the co-localization of aryl hydrocarbon receptor (AHR) and constitutive androstane receptor (CAR) in mouse neurons, points to the involvement of AHR and CAR in triclocarban-induced neurotoxicity. A 24-h treatment with triclocarban enhanced protein levels of the receptors which was paralleled by Car hypomethylation and Ahr hypermethylation. Car hypomethylation is in line with global DNA hypomethylation and explains the increased mRNA and protein levels of CAR in response to triclocarban. Ahr hypermethylation could reflect reduced Ahr mRNA expression and corresponds to lowered protein levels after 3- and 6-h exposures to triclocarban that is likely related to proteasomal degradation of activated AHR. We hypothesize that the triclocarban-induced apoptosis in mouse neurons and the disruption of epigenetic status involve both AHR- and CAR-mediated effects, which may substantiate a fetal basis of the adult onset of neurological diseases; however, the expression of the receptors is regulated in different ways.

Abstract

Background

Adjuvant trastuzumab improved overall survival and reduced the risk for disease recurrence in women with breast cancers, because of its potential cardiotoxicity, careful monitoring of left ventricular (LV) function during treatment is required.

Methods

This study investigates, whether myocardial strain imaging and level of N-terminal pro-brain natriuretic peptide (NT-pro BNP) could predict subsequent reduction in LVEF in breast cancer patients received adjuvant trastuzumab. 61 women with pathologically proven breast cancer HER-2 positive received AC (Doxorubicin–Cyclophosphamide) for 4 cycles, followed by paclitaxel with Trastuzumab were enrolled. Clinical, conventional echocardiographic parameters, myocardial strain imaging [global longitudinal peak systolic strain (GLS), radial and circumferential systolic strain] and level of NT pro-BNP were measured at baseline, after 3, 6, 9 and 12 months of trastuzumab therapy.

Results

Of 61 patients, 18 patients (29.5%) developed trastuzumab-induced cardiomyopathy (CM) at 6 and 9 months of therapy (LVEF declines?≥?10%), GLS and radial strain significantly decreased in CM group at 3 months of trastuzumab treatment, the value of GLS at 3 months was the strongest predictors of cardiotoxicity its area under the curve (AUC 0.98) with an optimal cut-off for GLS (??18%) having 92.5% sensitivity and 83% specificity. NT-pro BNP levels were not predictive of later trastuzumab-induced cardiac dysfunction.

Conclusion

Myocardial strain imaging has been able to predict pre-clinical changes in LV systolic function and GLS is an independent early predictor of subsequent reduction in EF in breast cancer patients treated with trastuzumab.

Keywords

Breast cancer Trastuzumab Cardiotoxicity Myocardial strain