Cardioprotective role of A-cycloglycosylated derivative of Rubiadin in diabetic cardiomyopathy in rats.

Diabetic cardiomyopathy (DCM) is a kind of idiopathic heart disease, which is one of the main complications of diabetes and seriously threatens the life of diabetic patients. Rubiadin, an anthraquinone compound extracted from the stems and roots of rubiaceae, has been widely discussed for its anti-diabetes, anti-oxidation and other pharmacological effects. However, Rubiadin can cause drug-induced liver injury. Therefore, A-cycloglycosylated derivative of Rubiadin (ACDR) was obtained by modifying its structure. The purpose of this study was to investigate the effect of ACDR on DCM cardiac injury and its mechanism. The DCM animal model was established by streptozotocin, and the success of DCM was verified by blood glucose level, echocardiographic evidence of impaired myocardial functions along with enhanced myocardial fibrosis. We performed liver function tests, morphological staining of the heart and tests for oxidative stress to evaluate cardiac functional and structural changes. Finally, the expression of Na+/H+ exchanger (NHE1) protein was analyzed by immunohistochemistry and western bolt, and the expression of hairy/enhancer-of-split related with YRPW motif 1 (Hey1) and P-p38 protein was detected by immunofluorescence chemistry and western blotting. The results showed that ACDR can improve cardiac dysfunction, reduce myocardial injury, reduce oxidative stress, and protect the liver in DCM rats. Interestingly, all variations were countered by LiCl. Our study suggests that, along with controlling hyperglycemia, ACDR may improve DCM by reducing NHE1 expression, further inhibiting P-p38 activity and increasing Hey1 expression to reduce oxidative stress.

Perillaldehyde improves cognitive function in vivo and in vitro by inhibiting neuronal damage via blocking TRPM2/NMDAR pathway.

BACKGROUND: Vascular cognitive dysfunction in patients with vascular dementia (VD) is a kind of severe cognitive dysfunction syndrome caused by cerebrovascular diseases. At present, effective drugs to improve the cognitive function of VD patients still need to be explored. Transient Receptor Potential Melastatin 2 (TRPM2) channel is a nonspecific cation channel that plays a key role in the toxic death of neurons. Perillaldehyde (PAE) has the protective effect of epilepsy and insomnia and other central nervous system diseases. The aim of this study is to explore whether PAE improves cognitive function in VD rats and to investigate the potential mechanisms in vivo and vitro. METHODS: VD rats were induced by bilateral common carotid arteries occlusion (2-vessel occlusion [2VO]) and treated with PAE for 4 weeks. The neuroprotective effects of PAE was subsequently assessed by the Morris water maze, hematoxylin-eosin (HE) staining, Golgi staining, electron microscopy, Neuron-specific nuclear protein (Neu N) staining, and TdT-mediated dUTP nick end labeling (TUNEL) staining. After primary hippocampal neurons were isolated, cell viability was detected by MTT assay and intracellular Ca2+ concentration was detected by calcium imaging assay. The content of Nitriteoxide (NO), Malondialdehyde (MDA) and Superoxide dismutase (SOD) activity in serum of rats were observed by Enzyme Linked Immunosorbent Assay (ELISA). Immunohistochemistry, Western blot, and Confocal laser scanning were used to detect the expression levels of N-methyl-D-asprtate receptor-2B (NR2B) and TRPM2. RESULTS: The results showed that PAE can improve the number and activity of neurons, increase the length and number of dendrites in hippocampus, decrease the Vv value and PE value of neuronal nucleus and mitochondrial structure significantly, increase the s value and L value in nucleus structure, decrease the s value and L value in mitochondrial structure, and improve the learning and memory ability of rats significantly. And PAE can strengthen the ability of antioxidant stress confirmed by increasing the activity of SOD and reducing the production of MDA. The results of western blot, immunohistochemistry and immunofluorescence showed that PAE could reduce the level of TRPM2 and increase the expression of NR2B. CONCLUSIONS: Taken together, our findings provide evidence that the neuroprotective effects of PAE in VD rats maybe through TRPM2 inhibition and subsequent activation of NMDAR signaling pathway.

Effects of simulated saliva-gastrointestinal digestion on the physicochemical properties and bioactivities of okra polysaccharides.

This study was to investigate the effects of in vitro simulated saliva-gastrointestinal digestion on the physicochemical properties and bioactivities of okra polysaccharides (OPS). Results showed that the digestibilities of OPS were about 5.1%, 37.5%, and 41.3% after saliva digestion (SD), saliva-gastric digestion (SGD), and saliva-gastrointestinal digestion (SGID), respectively. The SGID significantly changed the physicochemical properties of OPS, such as total uronic acids, total flavonoids, monosaccharide composition, rheological properties, and molecular weights (Mw). Especially, Mw changes resulted in the breakdown of glycosidic bonds during SGD, and the degradation of OPS during SGID was mainly caused by disrupting aggregates. Furthermore, the bioactivities of OPS were also affected by SGID. After SGID, OPS still possessed strong antioxidant activities, binding capacities, and prebiotic activities, but the α-glucosidase inhibitory effect was obviously decreased. Overall, results can provide valuable and scientific support on the oral administration of OPS as functional foods and medicines in the future.

Effectiveness of mammography screening in reducing breast cancer mortality in women aged 39-49 years: a meta-analysis.

BACKGROUND: Mammography screening of women >50 years of age significantly reduces breast cancer mortality in randomized controlled trials (RCTs). We sought to evaluate the effectiveness of mammography screening in women aged 39-49 years in reducing breast cancer mortality and to discuss previously published meta-analyses. METHODS: PubMed/MEDLINE, OVID, COCHRANE, and Educational Resources Information Center (ERIC) databases were searched, and extracted references were reviewed. Dissertation abstracts and clinical trials databases available online were assessed to identify unpublished works. All assessments were independently done by two reviewers. All trials included were RCTs, published in English, included data on women aged 39-49, and reported relative risk (RR)/odds ratio (OR) or frequency data. RESULTS: Nine studies were identified: the Kopparberg, Ostergotland (The Two-County study), Health Insurance Plan (HIP), Canada, Stockholm, Gothenburg, Edinburgh, Age, and Malmo trials. The individual trials were quality assessed, and the data were extracted using predefined forms. Using the DerSimonian and Laird random effects model, the results from the seven RCTs with the highest quality score were combined, and a significant pooled RR estimate of 0.83 (95% confidence interval [CI] 0.72-0.97) was calculated. Post hoc sensitivity analyses excluding studies with randomization before 1980 caused a loss of statistical significance (RR 0.87, 95% CI: 0.56, 1.13). CONCLUSIONS: Mammography screenings are effective and generate a 17% reduction in breast cancer mortality in women 39-49 years of age. The quality of the trials varies, and providers should inform women in this age group about the positive and negative aspects of mammography screenings.