Gold Nanobipyramid Hotspot Aggregation-Induced Surface-Enhanced Raman Scattering for the Ultrasensitive Detection of miRNA.

Herein, a surface-enhanced Raman scattering (SERS) biosensor was constructed by gold nanobipyramid (Au NBP) hotspot aggregation-induced SERS (HAI-SERS) for the ultrasensitive detection of microRNA-221 (miRNA-221). Impressively, compared with single Au NBP, the multiple Au NBPs assembled by tetrahedral DNA nanostructures (TDNs) could increase hotspot aggregation to significantly enhance the SERS signal of Raman molecule methylene blue (MB). Meanwhile, in the aid of Exo-III assisted target cycle amplification and TDNs-induced catalytic hairpin assembly (CHA) amplification, the biosensor could achieve the sensitive detection of miRNA-221 with a linear range of 1 fM-10 nM, and the limit of detection (LOD) was 0.59 fM, which could be used for practical application in MHCC-97L and MCF-7 cell lysates. This work provided a method for hotspot aggregation to enhance SERS for the detection of biomarkers and disease diagnosis.

Sirtuins family as a target in endothelial cell dysfunction: implications for vascular ageing.

The vascular endothelium is a protective barrier between the bloodstream and the vasculature that may be disrupted by different factors such as the presence of diseased states. Diseases like diabetes and obesity pose a great risk toward endothelial cell inflammation and oxidative stress, leading to endothelial cell dysfunction and thereby cardiovascular complications such as atherosclerosis. Sirtuins are NAD+-dependent histone deacetylases that are implicated in the pathophysiology of cardiovascular diseases, and they have been identified to be important regulators of endothelial cell function. A handful of recent studies suggest that disbalance in the regulation of endothelial sirtuins, mainly sirtuin 1 (SIRT1), contributes to endothelial cell dysfunction. Herein, we summarize how SIRT1 and other sirtuins may contribute to endothelial cell function and how presence of diseased conditions may alter their expressions to cause endothelial dysfunction. Moreover, we discuss how the beneficial effects of exercise on the endothelium are dependent on SIRT1. These mainly include regulation of signaling pathways related to endothelial nitric oxide synthase phosphorylation and nitric oxide production, mitochondrial biogenesis and mitochondria-mediated apoptotic pathways, oxidative stress and inflammatory pathways. Sirtuins as modulators of the adverse conditions in the endothelium hold a promising therapeutic potential for health conditions related to endothelial dysfunction and vascular ageing.

Lovastatin Prevents Depressive Behaviors and Increased Hippocampal Neurogenesis in Streptozotocin-Induced Diabetic Mice.

Depression is a progressive and chronic syndrome and commonly related to several neuropsychiatric comorbidities, of which depression is the most studied. Population-based studies have suggested a positive role of statins in ameliorating depression risk. However, the role of statins in the treatment of diabetes-related depression has not been well examined. Herein, we investigated the effects of lovastatin (LOV) on depressive phenotypes in streptozotocin-induced diabetic mice. The data suggested that the treatment of LOV at 10 or 20 mg/kg for 3 weeks markedly prevented diabetes-associated depressive behaviors reflected by better performance in the sucrose preference test, tail suspension test, and novelty-suppressed feeding test. The study further showed that these treatments improved the hippocampal neurogenesis as evidenced by increased bromodeoxyuridine-positive cells in the dentate gyrus with higher expression of mature brain-derived neurotrophic factor and increased phosphorylation of cAMP-response element-binding protein. As expected, diabetic mice treated with LOV showed significant improvement of hyperlipidemia rather than hyperglycemia. These results suggest that LOV may be employed as a drug for the treatment of diabetes-related depression.

Simvastatin prevents and ameliorates depressive behaviors via neuroinflammatory regulation in mice.

BACKGROUND: Statins play a beneficial role in the treatment of coronary artery disease and are widely prescribed to prevent hypercholesterolemia. Previous studies have demonstrated that statins also have anti-inflammatory and immunomodulatory properties, and these are being explored for potential benefits in depression. However, the role of statins in the treatment of depression has not been well examined. METHODS: We investigated the effects of simvastatin on depressive behaviors and neuroinflammation in lipopolysaccharide (LPS) and chronic mild stress (CMS) induced depression model in mice. Sucrose preference test (SPT), forced swimming test (FST), novelty-suppressed feeding test (NSFT) were used to detect the depressive behaviors. The microglial activation was detected by immunohistochemistry analysis and the pro-inflammatory cytokines expressions including IL-1ß, TNF-α and IL-6 were examined by Western blot analysis. RESULTS: Our data indicated that oral administration of simvastatin at 20 mg/kg significantly prevented and ameliorated depressive behaviors reflected by better performance in the SPT, FST and NSFT. Moreover, simvastatin markedly prevented and ameliorated LPS and CMS-induced neuroinflammation, as shown by the suppressed activation of microglia in hippocampus and decreased hippocampal pro-inflammatory cytokines expressions including IL-1ß, TNF-α, IL-6, which might be mediated via the inhibition of NF-κB pathway, as shown by the decreased nuclear NF-κB p65 expression. LIMITATIONS: The interpretation of the evidence of a positive treatment effect of simvastatin on the depressive manifestations, multifaceted etiology of depression, and confirmation of this finding from animal models to humans is needed. CONCLUSION: These results suggest that simvastatin has the potential to be employed as a therapy for depression associated with neuroinflammation.

Endothelial dysfunction in diabetes and hypertension: Role of microRNAs and long non-coding RNAs.

The vascular endothelium acts as a barrier between the blood flow and the inner lining of the vessel wall, and it functions as a filtering machinery to filter out any unwanted transfer of materials from both sides (i.e. the blood and the surrounding tissues). It is evident that diseases such as diabetes, obesity, and hypertension disturb the normal endothelial functions in humans and lead to endothelial dysfunction, which may further precede to the development of atherosclerosis. Long non-coding RNAs and micro RNAs both are types of non-coding RNAs which, in the recent years, have increasingly been studied in the pathophysiology of many diseases including diabetes, obesity, cardiovascular diseases, neurological diseases, and others. Recent findings have pointed out important aspects on their relevance to endothelial function as well as dysfunction of the system which may arise from presence of diseases such as diabetes and hypertension. Diabetes or hypertension-mediated endothelial dysfunction show characteristics such as reduced nitric oxide synthesis through suppression of endothelial nitric oxide synthase activity in endothelial cells, reduced sensitivity of nitric oxide in smooth muscle cells, and inflammation - all of which have been either shown to be directly caused by gene regulatory mechanisms of non-coding RNAs or shown to be having a correlation with them. In this review, we aim to discuss such findings on the role of these non-coding RNAs in diabetes or hypertension-associated endothelial dysfunction and the related mechanisms that may pave the way for alleviating endothelial dysfunction and its related complications such as atherosclerosis.

Berberine promotes nerve regeneration through IGFR­mediated JNK­AKT signal pathway.

Berberine presents therapeutic ability for various central nervous system disorders, including Alzheimer's disease and cerebral ischemia. The present study investigated the role of berberine in nerve regeneration and analyzed the potential mechanism mediated by berberine in hippocampal pyramidal neurons. Reverse transcription­quantitative poylmerase chain reaction, western blot, TUNEL assay and immunofluorescence were used to analyze the therapeutic effects of berberine on nerve regeneration. Berberine treatment increased growth and viability of hippocampal pyramidal neurons. Berberine treatment inhibited apoptosis of hippocampal pyramidal neurons and increased apoptosis regulator Bcl­2 and Bcl­w expression. Neuroinflammation of tumor necrosis factor α, interleukin (IL)1ß, IL6 levels and autophagy­related proteins microtubule­associated proteins 1A/1B light chain 3B, autophagy related 16 like 1 and autophagy related 7 were downregulated by berberine treatment in hippocampal pyramidal neurons. Notably, study has found that berberine increased insulin-like growth factor receptor (IGFR) and decreased c­Jun N­terminal kinase (JNK) and protein kinase B (AKT) expression in hippocampal pyramidal neurons. IGFR antagonist abolished berberine­increased growth of hippocampal pyramidal neurons. In conclusion, these results indicate that berberine can promote nerve regeneration through IGFR­mediated JNK­AKT signal pathway.

Betulin inhibits lipopolysaccharide/D-galactosamine-induced acute liver injury in mice through activating PPAR-γ.

Betulin is a phenolic flavonoid which has been reported to possess a mass of pharmacological properties, especially anti-inflammatory activity. The purpose of this study was to explore the protective effects and possible mechanism of betulin against lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced acute liver injury. D-Gal and LPS were intraperitoneally injected to develop acute liver injury animal model. Betulin (2, 4 or 8 mg/kg) were given 1 h before LPS/D-Gal instillation. Liver tissues and plasma samples were collected 9 h after LPS/D-Gal were given. The results indicated that betulin dramatically decreased liver pathologic changes, myeloperoxidase (MPO) activity, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Simultaneously, the levels of interleukin (IL-1ß) and tumor necrosis factor (TNF-α) in serum and liver tissues were both attenuated by betulin. Besides, betulin suppressed NF-κB pathway activation in a dose-dependently manner. Betulin increased the expression of PPAR-γ in a dose-dependent manner. In conclusion, all these results revealed that betulin could possess potential therapeutic effect for LPS/D-Gal-induced acute liver injury.

A one-dimensional silver(I) coordination polymer based on an asymmetric flexible N-donor carboxylate ligand: catena-poly[(µ3-4-{[(1-phenyl-1H-tetrazol-5-yl)sulfanyl]methyl}benzoato-κ(3)O:O':N(4))silver(I)].

The title compound, [Ag(C15H11N4O2S)]n, was synthesized by the reaction of 4-{[(1-phenyl-1H-tetrazol-5-yl)sulfanyl]methyl}benzoic acid (Hptmba) with silver nitrate and triethylamine at room temperature. The asymmetric unit contains one crystallographically independent Ag(I) cation and one ptmba(-) ligand. Each Ag(I) cation is tricoordinated by two carboxylate O atoms and one tetrazole N atom from three different ptmba(-) ligands, displaying a distorted T-shaped geometry. Three Ag(I) cations are linked by tris-monodentate bridging ptmba(-) ligands to form a one-dimensional double chain along the c axis, which is further consolidated by an intrachain π-π contact with an offset face-to-face distance of 4.176 (3) Å between the centroids of two adjacent aromatic rings in neighbouring benzoate groups. The one-dimensional chains are linked into a three-dimensional supramolecular framework by additional π-π interchain interactions, viz. of 3.753 (3) Å between two phenyl substituents of the tetrazole rings and of 4.326 (2) Å between a benzoate ring and a tetrazole ring. Thermogravimetric analysis and the fluorescence spectrum of the title compound reveal its good thermal stability and a strong green luminescence at room temperature.

[Epidemiological survey of the association between non alcoholic fatty liver disease and metabolic syndrome in civil servants of Chongqing city].

OBJECTIVE: To investigate the association between non alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS). METHODS: A cross-sectional multiple-stage stratified survey was performed. A total of 2190 civil servants of Chongqing city were invited to participate in the survey covering physical examination, serum biochemistry-profile and ultrasonographic examination of liver. RESULTS: Of 2176 valid questionnaires, altogether 455 cases were diagnosed as NAFLD and 231 individuals were diagnosed as MS. The prevalence of obesity, hyperglycemia, blood lipid disturbance, primary hypertension, NAFLD and MS was 38.3%, 5.5%, 31.7%, 29.9%, 20.9% and 10.6% respectively, which was increased along with aging (chi2 = 31.775, P = 0.000; chi2 = 25.985, P = 0.000; chi2 = 44.818, P = 0.000; chi2 =149.802, P = 0.000; chi2 = 61.302, P = 0.000; chi2 = 43.508, P = 0.000 a partly). The prevalence of obesity, hyperglycemia, dyslipidemia, primary hypertension, metabolic syndrome was significantly higher than those in control group (chi2 = 384.554, P = 0.000; chi2 = 25.597, P = 0.000; chi2 = 370.849, P = 0.000; chi2 = 40.252, P = 0.000; chi2 = 215.077, P = 0.000 separately), and the level of body mass index (BMI), fasting plasma glucose (FPG), triglyceride (TG), systolic blood pressure (SBP), diastolic blood pressure (DBP) in NAFLD group was remarkably higher than those in control group (t = 26.308, P = 0.000; t = 6.055, P = 0.000; t = 15.980, P = 0.000; t = 10.550, P = 0.000; t = 13.628, P = 0.000 respectively), while the level of high-density lipoprotein cholesterol (HDL-C) was on the opposite (t = 20.067, P = 0.000). Compared with the control group, odds risk for NAFLD was 22.82 folds (95% CI: 12.64-41.19) in obesity, 20.97 folds (95% CI: 11.21-39.24) in hyperglycemia, 24.40 folds (95% CI: 13.51-44.07) in dyslipidemia, 15.73 folds (95% CI: 8.66-28.60) in primary hypertension, while the risk for NAFLD was the highest in MS (OR = 31.06, 95% CI: 17.12-56.35). There were simple or multiple metabolic disorders in 455 individuals diagnosed as NAFLD, and 21 case (4.6%) with obesity, hyperglycemia, dyslipidemia and primary hypertension. CONCLUSION: NAFLD is closely related with MS, which may be considered as a feature of MS.