Independent and combined effects of liraglutide and aerobic interval training on glycemic control and cardiac protection in diabetic cardiomyopathy rats.

OBJECTIVE: This study intended to explore the hypoglycemic and cardioprotective effects of 8-week aerobic interval training combined with liraglutide and elucidate the underlying mechanisms. METHOD: Male Wistar rats were randomly divided into 5 groups - normal control group (CON), diabetic cardiomyopathy group (DCM), high-dose liraglutide group (DH), low-dose liraglutide group (DL), and aerobic interval training combined with liraglutide group (DLE). High-fat diet and streptozotocin (STZ) were used to induce the DCM model, and both the liraglutide administration group and combination therapy group allocated to 8 weeks of either liraglutide or liraglutide and exercise intervention. Cardiac functions were analyzed by electrocardiography. Blood biochemical parameters were measured to judge glycemic control conditions. Hematoxylin and eosin (HE) staining and Sirus red staining was used to identify cardiac morphology and collagen accumulation, respectively. Advanced glycation end products (AGEs) were determined by enzymatic methods. The mRNA expression of myocardial remodeling genes (BNP, GSK3ß, α-MHC, ß-MHC and PPARα) and the protein expression of GLP-1, GLP-1R were analyzed. RESULTS: DCM rats developed hyperglycemia, impaired cardiac function with accumulation of AGEs and collagen (P < 0.05). The development of hyperglycemia and cardiac dysfunction was significantly attenuated with all interventions, as reduced cardiac fibrosis and improved cardiac function (P < 0.05). Cardiac remodeling genes were normalized after all interventions, these positive modifications were due to increased GLP-1 and GLP-1R expression in DCM heart (P < 0.05). Liraglutide combined with AIT significantly increased the diameters of cardiomyocytes, increased the α-MHC expressionx, reduced PPARαexpression and reduced the fluctuation of blood glucose level, which showed the safety and effective of medicine combined with exercise. CONCLUSION: Liraglutide combined with AIT intervention normalized blood glucose alleviates myocardial fibrosis and improves cardiac contractile function in DCM rats, supporting the efficacy and safety of the combination therapy.

LncRNA SBF2-AS1 inhibits apoptosis and promotes proliferation in lung cancer cell via regulating FOXM1.

PURPOSE: To discover pivotal long non-coding ribonucleic acids (lncRNAs) in lung cancer, and to explore the related molecular mechanism by which the lncRNAs affect lung cancer cells. METHODS: The differentially expressed lncRNAs and messenger RNAs (mRNAs) in cancer tissues and paracancer tissues in lung cancer patients were first excavated via gene chips. Then, the differentially expressed lncRNAs were verified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The key genes were screened from the differentially expressed genes using bioinformatics, and their correlations with the expression levels of lncRNAs were explored using Pearson's correlation coefficient. Finally, overexpression and knockdown techniques were employed to verify the influences of changes in the content of lncRNAs and relevant genes on the proliferation and apoptosis of lung cancer A546 cells. RESULTS: The expression profiles of lncRNAs and mRNAs showed notable differences between cancer and paracancer tissues in lung cancer patients, and 28 differentially expressed lncRNAs and 914 differentially expressed mRNAs were screened. Through the survival analysis, it was found that the expression levels of SBF2-antisense RNA 1 (AS1) and LINC00968 had significant influence on the survival of patients. The Pearson's correlation coefficient analysis results revealed that the expression level of SBF2-AS1 was positively correlated with the core genes forkhead box protein M1 (FOXM1), the cyclin-dependent kinase 1(CDK1), centromere protein F (CENPF), cyclin B2 (CCNB2), and cell division cycle 20 (CDC20). The CCK-8 and EdU assay results showed that the proliferation ability of lung cancer A549 cells was enhanced in lncRNA SBF2-AS1 overexpression group, and that their proliferation rate was substantially lowered, when FOXM1 was knocked down. CONCLUSIONS: Both lncRNA SBF2-AS1 and FOXM1 play crucial roles in the pathological process of lung cancer, and lncRNA SBF2-AS1 up-regulates FOXM1 to inhibit the apoptosis of lung cancer cells, and promote their proliferation.

Correlations between hormone levels and cardiovascular autonomic neuropathy in menopausal patients with diabetes mellitus.

OBJECTIVE: To discuss the correlation between hormone levels and cardiovascular autonomic neuropathy (CAN) in menopausal patients with Type-2 diabetes mellitus (T2DM). METHODS: This clinical research study was conducted at Department of Endocrinology, Baoding No. 1 Hospital from January 2016 to December 2017. In this study a total of 386 menopausal female patients with T2 DM were selected and classified into two groups according to the CAN function test: the CAN group (80 cases) and the DM group (306 cases). The Kupperman score (KI integral) was calculated for all participants in the study, and the following indexes were measured: body mass index (BMI), blood estrogen (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), fasting blood-glucose (FBG), glycosylated hemoglobin (HbA1c), serum lipids, uric acid (SUA), hypersensitive c-reactive protein (CRP), etc. RESULTS: The FBG, HbA1c, TGs, Hs-CRP, SUA, KI score, TSH, FSH and LH of the CAN group were obviously higher than the same parameters in the DM group (P<0.01, P<0.05), while HDL-C, E2, FT3 and FT4 were significantly lower (Pπ.01, Pπ.05). Pearson correlation analysis indicated that CAN presents a positive correlation with HbA1c, TGs, hs-CRP and SUA and a negative correlation with HDL-C and E2, and the difference was statistically significant (P<0.05). The multifactor logistic regression analysis results showed that HbA1c (OR=3.980, 95%CI=1.268~10.319) and E2 (OR=3.075, 95%CI=1.167~7.366) are independent risk factors for CAN. CONCLUSION: The CAN morbidity of menopausal female patients with T2DM is high, and HbA1c and E2 should be mainly monitored to identify and treat CAN early.

An attempt to reverse cardiac lipotoxicity by aerobic interval training in a high-fat diet- and streptozotocin-induced type 2 diabetes rat model.

BACKGROUND: Diabetes mellitus (DM) is an important risk factor for cardiovascular disease. Aerobic interval training (AIT) has been recommended to patients as a non-pharmacological strategy to manage DM. However, little is known about whether AIT intervention at the onset of DM will reverse the process of diabetic cardiomyopathy (DCM). In this study, we sought to evaluate whether AIT can reverse the process of DCM and explore the underlying mechanisms. METHODS: Fifty Wistar rats were randomly divided into a control group (CON), DCM group (DCM) and AIT intervention group (AIT). A high-fat diet and streptozotocin (STZ) were used to induce diabetes in rats in the DCM group and AIT group. Rats in the AIT group were subjected to an 8-week AIT intervention. Fasting blood glucose (FBG), lipid profiles and insulin levels were measured. Haematoxylin and eosin (HE) staining and oil red O staining were used to identify cardiac morphology and lipid accumulation, respectively. Serum BNP levels and cardiac BNP mRNA expression were measured to ensure the safety of the AIT intervention. Free fatty acid (FFA) and diacylglycerol (DAG) concentrations were analysed by enzymatic methods. AMPK, p-AMPK, FOXO1, CD36 and PPARα gene and protein expression were detected by RT-PCR and Western blotting. RESULTS: AIT intervention significantly reduced rat serum cardiovascular disease risk factors in DCM rats (P < 0.05). The safety of AIT intervention was illustrated by reduced serum BNP levels and cardiac BNP mRNA expression (P < 0.05) after AIT intervention in DCM rats histological analysis and FFA and DAG concentrations revealed that AIT intervention reduced the accumulation of lipid droplets within cardiomyocytes and alleviated cardiac lipotoxicity (P < 0.05). CD36 and PPARα gene and protein expression were elevated in the DCM group, and these increases were reduced by AIT intervention (P < 0.01). The normalized myocardial lipotoxicity was due to increased expression of phosphorylated AMPK and reduced FOXO1 expression after AIT intervention. CONCLUSION: AIT intervention may alleviate cardiac lipotoxicity and reverse the process of DCM through activation of the AMPK-FOXO1 pathway.

Occurrence of quaternary ammonium compounds (QACs) and their application as a tracer for sewage derived pollution in urban estuarine sediments.

Particle reactive organic contaminants in estuarine sediments can lead to various environmental problems affecting ecosystem and public health. In this study, the occurrence and homologous distribution pattern of quaternary ammonium compounds (QACs) in the surficial sediments collected from the Pearl River Estuary (PRE), China were examined along with polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs). The composition pattern of the QACs was found to be uniform in most of the sediments analyzed throughout the PRE, and the average composition pattern was identical to that determined in the sewage sludge from Guangzhou, the biggest city in the PRE. Dialkyldimethylammonium compounds, the most abundant type of QACs, positively correlated to the total concentrations of PCBs and PBDEs in most of the sediments with similar composition patterns. Therefore, the QACs are proposed as potential tracers to evaluate the transport of sewage-derived pollution in estuarine environments.

Bioaccumulation of trace metals in farmed fish from South China and potential risk assessment.

Concentrations of trace metals were determined in water, sediment, fish feed and two species of farmed fish, pompano and snapper, collected from Daya Bay and Hailing Bay of South China in July 2007 and January 2008. Total average concentrations of Cu, Pb, Zn, Cd, Cr, Hg and As were 1.6, 2.7, 27.3, 0.025, 0.62, 0.18 and 0.59 µg/g dry wt in pompano and 1.5, 2.6, 23.6, 0.020, 0.55, 0.22 and 0.53 µg/g dry wt in snapper. In general, the concentrations of all target metals except Hg were positively correlated with lipid contents whereas negative correlations were observed between the metal concentrations and fish body weights. Model calculation indicated that dietary uptake of Zn and Cd predominate their accumulation in snapper, accounting for 99.9% and 98.2% of the total inputs. Risk assessments suggested that potential ecological and human health risk may be present due to elevated Pb concentrations in sediment and farmed fish.