Abstract

The  aim of the study was to evaluate the hypoglycaemic potential of  supplementary Cr in the form of chromium(III) glycinate (CrGly) in the  diabetic model of rats. The experiment was conducted on 40 male Wistar  rats, of which 30 were made diabetic by injection of a single dose of  streptozotocin (55 mg/kg b.m.), while the remaining 10 rats served as  the healthy control. After inducing hyperglycaemia, 2 groups of diabetic  rats (10 rats each) were supplemented with Cr either as CrGly or  chromium(III) picolinate (CrPic) given orally at a dose of 10 mg/kg diet  (about 0.75 mg Cr/kg b.m.) with adequate AIN-93M diet for 7 weeks. At  the termination of experiment, all animals were sacrificed to collect  blood and internal organs for biochemical assays. Blood biochemical  indices and tissular trace element contents (Fe, Zn, Cu, Cr) were  measured and compared with the values of the untreated groups. It was  found that CrGly significantly decreased blood glucose, total  cholesterol, HDL cholesterol and triacylglycerol levels more efficiently  than CrPic. Furthermore, both Cr compounds normalized disturbed the  serum, renal and cardiac molar Cu/Zn ratio, as well as restored the  kidney Zn and Cu levels in rats with hyperglycaemia. Supplementary Cr  did not increase the tissular Cr levels in diabetic rats. The study  confirmed the hypoglycaemic potential of CrGly in the diabetic model of  rats.

Abstract

Long-term memory impairment is reported in more than 50% of cardiac arrest survivors. Monosialoganglioside (GM1) provided neuroprotection in experimental models of stroke but failed to replicate its promise clinically for unknown reasons. GM1 stimulates the release of nerve growth factor (NGF), which is synthesized as a precursor protein (pro-NGF) that either mediates apoptosis through the p75 neurotrophin receptor (p75NTR) or is cleaved by the protease furin (FUR) to yield mature NGF, the latter supporting survival through tropomyosin kinase receptor (Trk). The flavanol epicatechin (EPI) inhibits p75NTR-mediated signaling and apoptosis by pro-NGF. The aim of the current work is to test whether these two drugs affect, or communicate with, each other in the setting of CNS injuries. Using the two-vessel occlusion model of global ischemia/reperfusion (I/R), we tested if pharmacological modulation of Trk, p75NTR, and NGF balance with GM1, EPI, and their combination, can correct the memory deficit that follows this insult. Finally, we tested if FUR insufficiency and/or p75NTR-mediated apoptosis negatively affect the neurotherapeutic effect of GM1. Key proteins for Trk and p75NTR, FUR, and both forms of NGF were assessed. All treatment regiments successfully improved spatial memory retention and acquisition. A week after the insult, most Trk and p75NTR proteins were normal, but pro/mature NGF ratio remained sharply elevated and was associated with the poorest memory performance. Pharmacological correction of this balance was achieved by reinforcing Trk and p75NTR signaling. GM1 increased FUR levels, while concomitant administration of EPI weakened GM1 effect on pro-survival Trk and p75NTR mediators. GM1 neuroprotection is therefore not limited by FUR but could be dependent on p75NTR.

Abstract

Background

Angiopoietin-like protein 8 (ANGPTL8), a newly identified hormone, has been recently characterized as a metabolic regulator which can affect energy homeostasis and has interesting potentials as a metabolic disease therapy. However, little is as yet known as to whether circulating ANGPTL8 levels are altered in thyroid dysfunction. This study measured serum ANGPTL8 levels in patients with Graves’ disease and explored the correlations between its serum levels and thyroid index in Graves’ disease.

Methods

The concentration of ANGPTL8 was analyzed in blood samples of 128 well-characterized individuals whose anthropometric parameters, biochemical parameters, and thyroid index were measured. The participants were divided into Graves’ disease patients (n?=?60) and healthy control subjects (n?=?68). Logistic regression was used to evaluate the relationship between ANGPTL8 and Graves’ disease.

Results

Serum ANGPTL8 levels were more significantly decreased in Graves’ disease patients than in healthy control subjects (177.67 ±?135.07 vs 326.41?±?194.72 pg/mL; p?<?0.001). Serum ANGPTL8 was negatively correlated with free triiodothyronine (FT3), free thyroxine (FT4), and thyroid peroxidase antibodies (TPOAb) while being positively correlated with thyrotropin (TSH). Logistic regression analyses demonstrated that serum ANGPTL8 was significantly associated with Graves’ disease (p <?0.05).

Conclusions

Circulating concentrations of ANGPTL8 showed a significant reduction in Graves’ disease patients. Thus, it is suggested that thyroid function should be taken into consideration when evaluating the results of ANGPTL8.

Abstract

Mesenchymal stem cell transplantation can regulate neuroinflammation and treat Alzheimer's disease (AD), but its effect is attenuated by in vitro expansion. To solve this problem, we used tanshinone IIA (TIIA)-incubated mesenchymal stem cells (MSCs) to treat neuroinflammation caused by amyloid β-protein (Aβ). Here, we demonstrated that behavioral performance was rescued in rats receiving an intracerebroventricular injection of TIIA-incubated MSCs (TIIA-MSCs), and the TIIA-MSCs protected against neurotoxicity in the rat hippocampus by suppressing Aβ25-35-induced neuroinflammation. The levels of interleukin-1 (IL-1), IL-4, IL-6, IL-10 and tumor necrosis factor α (TNF-α) in Aβ25-35-induced rats were attenuated by TIIA-MSCs treatment, and IL-6 was the key difference between the TIIA-MSCs and MSCs groups. Furthermore, TIIA-MSCs reduced Aβ production-related mRNA (BACE1 and PS1) expression but had no significant effect on clearance (AMDM10). TIIA-MSCs also had the same effects on the protein levels. For the first time, we found that TIIA-MSCs have greater neuroprotective effects and prevent toxic protein production better than MSCs. These effects are related to Aβ modulation via downregulated BACE1 expression that promotes the survival of hippocampal neurons, as well as regulates neuroinflammatory-associated cytokines. These results provide support for the clinical application of MSCs, which will bring new hope for the treatment of AD.

Abstract

Beta-caryophyllene (BCP) is a phytocannabinoid possessing selective agonistic activity to cannabinoid type-2 receptors (CB2R) and peroxisome proliferator-activated receptors-α (PPAR-α). However, few studies reported the contribution of PPAR-γ receptors in BCP effects. The aim of this study was to investigate the BCP effects on diet-induced dyslipidemia and vascular inflammation as well as the involvement of CB2R and PPAR-γ receptors. Wistar rats were fed a high-fat diet and administered 10% fructose for 12 weeks. Treatment with pioglitazone, BCP, BCP + CB2R antagonist, AM630, or BCP + PPAR-γ antagonist, BADGE was started from the 9th week and continued till the 12th week. BCP significantly ameliorated all diet-induced alterations in a CB2R-dependant manner as it improved glycemic parameters, dyslipidemia, and vascular oxidative stress and inflammation. It also downregulated proatherogenic adhesion molecule (VCAM-1) and restored vascular eNOS/iNOS expression balance. PPAR-γ was involved in BCP-evoked suppression of vascular inflammation, VCAM-1 and restoration of normal vascular eNOS/iNOS balance thus normal NO level. Furthermore, part of BCP hypolipidemic effects (lowering total cholesterol, LDL, VLDL) involved both CB2R and PPAR-γ receptors. BCP treatment was superior to pioglitazone in anti-inflammatory and anti-atherosclerotic measures. BCP may represent a more potent alternate to pioglitazone avoiding its side effects in the treatment of insulin resistance and vascular inflammation.