Potential of resveratrol in anticancer and anti-inflammatory therapy

Phytochemicals present in food have shown significant prospects in the treatment and management of a vast array of human diseases. Resveratrol is a stilbene-type aromatic phytoalexin predominantly found in grapes, peanuts, berries, turmeric, and other food products. Resveratrol has been reported to exhibit several physiological activities including anticancer and anti-inflammatory activities in vitro and in experimental animal models, as well as in humans. Anticancer activity of this compound is mainly due to induction of apoptosis via several pathways, as well as alteration of gene expressions, all leading to a decrease in tumor initiation, promotion, and progression. Resveratrol exhibits anti-inflammatory activity through modulation of enzymes and pathways that produce mediators of inflammation and also induction of programmed cell death in activated immune cells. Resveratrol has been shown to produce no adverse effects, even when consumed at high concentrations. Hence, resveratrol possesses good potential to be used as an adjunctive or alternative therapy for cancer and inflammatory diseases.     

Identification of Tibial Malrotation After Nailing Using Unique CT Scan Reference Line,and Influence of Position of Leg for Distal Locking on Rotation

IntroductionTibial torsion can be measured by various clinical and radiological methods. Computed tomography (CT) scan measurement is currently the investigation of choice. The purpose of our study was to compare the clinical and CT scan methods to reveal malrotation after nailing of tibia and also to find out if leg position for distal locking has any influence on incidence of malrotation.Materials and methodsWe have included 106 patients (21–68 years) of tibia nailing, and categorised them as category A (figure of four position n = 54) and category B (knee straight position n = 52) based on limb position for distal locking. The plumb line measurement, Thigh Foot Axis (TFA) and CT scan measurement (using new reference line) were documented and compared with the uninjured limb.ResultsWe observed plumb line measurement to be the most inaccurate method followed by TFA method. CT scan measurement was the most accurate method showing external rotations (> 10º) in 32 cases (30.1%) and internal rotation (> − 10º) in five cases (4.71%). The TFA method had a sensitivity of 44% and specificity of 86% in identifying malrotations. The interobserver reliability for CT scan measurement was 0.96. Even though statistically not significant (P value), figure of four position for distal locking leads to larger number of malrotations (both external and internal rotation).ConclusionCT scan is the most accurate method of measuring malrotation. The new reference line used in our study provides accurate measurement of malrotation. The two different positions of leg for distal locking do not have a statistically significant influence on incidence of malrotation.     

Phytosterols protect against diet-induced hypertriglyceridemia in Syrian golden hamsters

Background

In addition to lowering LDL-C, emerging data suggests that phytosterols (PS) may reduce blood triglycerides (TG), however, the underlying mechanisms are not known.

Methods

We examined the TG-lowering mechanisms of dietary PS in Syrian golden hamsters randomly assigned to a high fat (HF) diet or the HF diet supplemented with PS (2%) for 6 weeks (n?=?12/group). An additional subset of animals (n?=?12) was provided the HF diet supplemented with ezetimibe (EZ, 0.002%) as a positive control as it is a cholesterol-lowering agent with known TG-lowering properties.

Results

In confirmation of diet formulation and compound delivery, both the PS and EZ treatments lowered (p?<?0.05) intestinal cholesterol absorption (24 and 31%, respectively), blood non-HDL cholesterol (61 and 66%, respectively), and hepatic cholesterol (45 and 55%, respectively) compared with the HF-fed animals. Blood TG concentrations were lower (p?<?0.05) in the PS (49%) and EZ (68%)-treated animals compared with the HF group. The TG-lowering response in the PS-supplemented group was associated with reduced (p?<?0.05) intestinal SREBP1c mRNA (0.45 fold of HF), hepatic PPARα mRNA (0.73 fold of HF), hepatic FAS protein abundance (0.68 fold of HD), and de novo lipogenesis (44%) compared with the HF group. Similarly, lipogenesis was lower in the EZ-treated animals, albeit through a reduction in the hepatic protein abundance of ACC (0.47 fold of HF).

Conclusions

Study results suggest that dietary PS are protective against diet-induced hypertriglyceridemia, likely through multiple mechanisms that involve modulation of intestinal fatty acid metabolism and a reduction in hepatic lipogenesis.     

ACE2 Deficiency Worsens Epicardial Adipose Tissue Inflammation and Cardiac Dysfunction in Response to Diet-Induced Obesity

Obesity is increasing in prevalence and is strongly associated with metabolic and cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; angiotensin (Ang)-converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. We studied the role of ACE2 in obesity-mediated cardiac dysfunction. ACE2 null (ACE2KO) and wild-type (WT) mice were fed a high-fat diet (HFD) or a control diet and studied at 6 months of age. Loss of ACE2 resulted in decreased weight gain but increased glucose intolerance, epicardial adipose tissue (EAT) inflammation, and polarization of macrophages into a proinflammatory phenotype in response to HFD. Similarly, human EAT in patients with obesity and heart failure displayed a proinflammatory macrophage phenotype. Exacerbated EAT inflammation in ACE2KO-HFD mice was associated with decreased myocardial adiponectin, decreased phosphorylation of AMPK, increased cardiac steatosis and lipotoxicity, and myocardial insulin resistance, which worsened heart function. Ang 1-7 (24 µg/kg/h) administered to ACE2KO-HFD mice resulted in ameliorated EAT inflammation and reduced cardiac steatosis and lipotoxicity, resulting in normalization of heart failure. In conclusion, ACE2 plays a novel role in heart disease associated with obesity wherein ACE2 negatively regulates obesity-induced EAT inflammation and cardiac insulin resistance.