Overexpressed ski efficiently promotes neurorestoration, increases neuronal regeneration, and reduces astrogliosis after traumatic brain injury.

Traumatic brain injury (TBI) survivors suffer from long-term disability and neuropsychiatric sequelae due to irreparable brain tissue destruction. However, there are still few efficient therapies to promote neurorestoration in damaged brain tissue. This study aimed to investigate whether the pro-oncogenic gene ski can promote neurorestoration after TBI. We established a ski-overexpressing experimental TBI mouse model using adenovirus-mediated overexpression through immediate injection after injury. Hematoxylin-eosin staining, MRI-based 3D lesion volume reconstruction, neurobehavioral tests, and analyses of neuronal regeneration and astrogliosis were used to assess neurorestorative efficiency. The effects of ski overexpression on the proliferation of cultured immature neurons and astrocytes were evaluated using imaging flow cytometry. The Ski protein level increased in the perilesional region at 3 days post injury. ski overexpression further elevated Ski protein levels up to 14 days post injury. Lesion volume was attenuated by approximately 36-55% after ski overexpression, with better neurobehavioral recovery, more newborn immature and mature neurons, and less astrogliosis in the perilesional region. Imaging flow cytometry results showed that ski overexpression elevated the proliferation rate of immature neurons and reduced the proliferation rate of astrocytes. These results show that ski can be considered a novel neurorestoration-related gene that effectively promotes neurorestoration, facilitates neuronal regeneration, and reduces astrogliosis after TBI.

A2A R inhibition in alleviating spatial recognition memory impairment after TBI is associated with improvement in autophagic flux in RSC.

Spatial recognition memory impairment is an important complication after traumatic brain injury (TBI). We previously found that spatial recognition memory impairment can be alleviated in adenosine A2A receptor knockout (A2A R KO) mice after TBI, but the mechanism remains unclear. In the current study, we used manganese-enhanced magnetic resonance imaging and the Y-maze test to determine whether the electrical activity of neurons in the retrosplenial cortex (RSC) was reduced and spatial recognition memory was impaired in wild-type (WT) mice after moderate TBI. Furthermore, spatial recognition memory was damaged by optogenetically inhibiting the electrical activity of RSC neurons in WT mice. Additionally, the electrical activity of RSC neurons was significantly increased and spatial recognition memory impairment was reduced in A2A R KO mice after moderate TBI. Specific inhibition of A2A R in the ipsilateral RSC alleviated the impairment in spatial recognition memory in WT mice. In addition, A2A R KO improved autophagic flux in the ipsilateral RSC after injury. In primary cultured neurons, activation of A2A R reduced lysosomal-associated membrane protein 1 and cathepsin D (CTSD) levels, increased phosphorylated protein kinase A and phosphorylated extracellular signal-regulated kinase 2 levels, reduced transcription factor EB (TFEB) nuclear localization and impaired autophagic flux. These results suggest that the impairment of spatial recognition memory after TBI may be associated with impaired autophagic flux in the RSC and that A2A R activation may reduce lysosomal biogenesis through the PKA/ERK2/TFEB pathway to impair autophagic flux.

NLRC3 silencing accelerates the invasion of hepatocellular carcinoma cell via IL-6/JAK2/STAT3 pathway activation.

Nucleotide-binding domain, leucine-rich repeat family with a caspase activation and recruitment domain 3 (NLRC3) participates in both immunity and cancer. The aim of this study was to determine the role of NLRC3 in human hepatocellular carcinoma (HCC) and the underlying mechanisms. We collected human liver tissues from nonalcoholic steatohepatitis (NASH), HCC, and adjacent normal tissues to characterize the pattern of NLRC3 expression by real-time quantitative polymerase chain reaction and immunohistochemistry. Then, we used the HCC cell line, HuH-7, transfected with small interfering RNA to silence the NLRC3 expression. 5-Ethynyl-2'-deoxyuridine assay, scratch assay, and transwell invasion assay were used for assessing proliferation, migration, and invasion, respectively. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were conducted to assess cell apoptosis. The expression of NLRC3 was reduced in human HCC tissues, compared with normal liver and nonalcoholic steatohepatitis tissues. After knocking down of NLRC3, the proliferation, migration, and invasion were increased in HuH-7 cells. And flow cytometry and TUNEL assay showed that HuH-7 cell apoptosis was suppressed after NLRC3 knockdown. As for the underlying mechanisms, knockdown of NLRC3 in HuH-7 cells was associated with the activation of Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) pathway under interleukin-6 (IL-6) stimulation. NLRC3 expression was downregulated in human HCC tissues. NLRC3 silencing in HuH-7 cells can promote the proliferation, migration, and invasion of hepatocellular carcinoma cells. JAK2/STAT3 pathway activation induced by IL-6 may be the underlying mechanism for HCC when NLRC3 expression is silenced. And the invasion of HuH-7 cells was partially suppressed by the STAT3 specific inhibitor (cryptotanshinone). Therefore, NLRC3 may play a significant role in HCC and might be a therapeutic target for the treatment of HCC.

Pathogenic mechanism of a catecholaminergic polymorphic ventricular tachycardia causing-mutation in cardiac calcium release channel RyR2.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a condition that is characterized by an abnormal heart rhythm in response to physical or emotional stress. The majority CPVT patients carry mutations in the RYR2 gene that encodes the calcium release channel/ryanodine receptor (RyR2) in cardiomyocytes. The pathogenic mechanisms that account for the clinical phenotypes of CPVT are still elusive. We have identified a de novo mutation, A165D, from a CPVT patient. We found that CPVT phenotypes are recapitulated in A165D knock-in mice. The mutant RyR2 channels enhanced sarcoplasmic reticulum Ca2+ release, triggered delayed afterdepolarization in cardiomyocytes. Structural analysis revealed that the A165D mutation is located in a loop that is involved in inter-subunit interactions in the RyR2 tetrameric structure, it disrupted conformational stability of the RyR2, which favored a closed-to-open state transition, resulting in a leaky channel. The loop also harbors several other CPVT mutations, which suggests a common pathogenic molecular mechanism of CPVT-causing mutations. Our data illustrated disease-relevant functional defects and provide a deeper mechanistic understanding of a life-threatening cardiac arrhythmia.

Diosgenin Protects Rats from Myocardial Inflammatory Injury Induced by Ischemia-Reperfusion.

BACKGROUND Diosgenin, a phytosteroid sapogenin, has anti-inflammatory properties shown to reduce myocardial ischemia-reperfusion injury (MIRI). However, the specific mechanism by which this is achieved is not clear. This study investigated the protective effects of diosgenin on myocardial ischemia/reperfusion (I/R) and the potential anti-inflammatory mechanisms. MATERIAL AND METHODS Healthy adult male SD rats, body weight (b.w.) 250-280 g, were used to model ischemia-reperfusion injury (IRI) and were administered diosgenin (50 mg/kg and 100 mg/kg b.w.) intragastrically for 4 consecutive weeks before surgery. The left anterior descending artery (LAD) was ligated to induce myocardial ischemia for 30 min and reperfusion for 30 min, 60 min, and 120 min while relevant indicators were detected. RESULTS Both 50 mg and 100 mg diosgenin oral administration increased left ventricular developed pressure (LVDP) and maximum changing rate of ventricular pressure (±dp/dtmax), decreased left ventricular end-diastolic pressure (LVEDP), and myocardial enzyme markers. TTC staining suggested that diosgenin reduced myocardial infarct size in the rat model. Pathological results showed that myocardial ischemia and inflammation were alleviated by diosgenin. In addition, the increased expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) in serum, and myeloperoxidase (MPO) in myocardium were significantly suppressed by diosgenin administration. Diosgenin further inhibited the phosphorylation of transcription factor NF-κB and modulated the expression of downstream inflammatory cytokines by regulating the activation of p38-MAPK and JNK pathways. CONCLUSIONS Results demonstrate diosgenin plays an anti-inflammatory role in the protection of MIRI through regulation of p38-MAPK and JNK pathways and phosphorylation of NF-κB.

Comparison of various lipid parameters in association of target organ damage: a cohort study.

BACKGROUND: Recommendations of non-HDL amplification varied from different guidelines. We aim to test the relationships between various lipid parameters and target organ damage (TOD) including aortic stiffness, peripheral arterial disease and chronic kidney disease in a community-based elderly cohort. METHODS: 1599 (aged 71.4 ± 6.1 years) participants were recruited. Eight lipid parameters, including total cholesterol (TC), triglycerides (TG), LDL-C, HDL-C, non-HDL-C, TC/HDL ratio, TG/HDL ratio and LDL/HDL ratio, together with other plasma biomarkers like creatinine were measured. Pulse wave velocity (PWV) was measured by the SphygmoCor device, and ankle-brachial index (ABI) was assessed by Omron VP-1000 device. RESULTS: Four individual lipid parameters (TC, TG, LDL-C and HDL-C) significantly correlated with most, but not all, TOD indices. Meanwhile, 4 combined lipid parameters, namely non-HDL-C, TC/HDL, TG/HDL and LCL/HDL, significantly correlated with all TOD (P ≤ 0.033). In multiple linear regression analyses, 4 combined lipid parameters also significantly associated with TOD (P ≤ 0.027), while none of individual lipid parameters significantly associated with all TOD indices. In multiple logistic regression analyses, only non-HDLC and TC/HDL significantly associated with TOD (P ≤ 0.039), and other lipid parameters did not significantly associate with TOD. CONCLUSION: In an elderly community sample, non-HDLC and TC/HDLC were better associated with TOD than other lipid parameters. This finding should be considered in future clinical lipid-lowing therapy. TRIAL REGISTRATION: This trial was retrospectively registered in ClinicalTrials.gov (No. NCT02368938 , registered on 15 Feb 2015).

Dual specific phosphatase 12 ameliorates cardiac hypertrophy in response to pressure overload.

Pathological cardiac hypertrophy is an independent risk factor of heart failure. However, we still lack effective methods to reverse cardiac hypertrophy. DUSP12 is a member of the dual specific phosphatase (DUSP) family, which is characterized by its DUSP activity to dephosphorylate both tyrosine and serine/threonine residues on one substrate. Some DUSPs have been identified as being involved in the regulation of cardiac hypertrophy. However, the role of DUSP12 during pathological cardiac hypertrophy is still unclear. In the present study, we observed a significant decrease in DUSP12 expression in hypertrophic hearts and cardiomyocytes. Using a genetic loss-of-function murine model, we demonstrated that DUSP12 deficiency apparently aggravated pressure overload-induced cardiac hypertrophy and fibrosis as well as impaired cardiac function, whereas cardiac-specific overexpression of DUPS12 was capable of reversing this hypertrophic and fibrotic phenotype and improving contractile function. Furthermore, we demonstrated that JNK1/2 activity but neither ERK1/2 nor p38 activity was increased in the DUSP12 deficient group and decreased in the DUSP12 overexpression group both in vitro and in vivo under hypertrophic stress conditions. Pharmacological inhibition of JNK1/2 activity (SP600125) is capable of reversing the hypertrophic phenotype in DUSP12 knockout (KO) mice. DUSP12 protects against pathological cardiac hypertrophy and related pathologies. This regulatory role of DUSP12 is primarily through c-Jun N-terminal kinase (JNK) inhibition. DUSP12 could be a promising therapeutic target of pathological cardiac hypertrophy. DUSP12 is down-regulated in hypertrophic hearts. An absence of DUSP12 aggravated cardiac hypertrophy, whereas cardiomyocyte-specific DUSP12 overexpression can alleviate this hypertrophic phenotype with improved cardiac function. Further study demonstrated that DUSP12 inhibited JNK activity to attenuate pathological cardiac hypertrophy.

TBX5 loss-of-function mutation contributes to familial dilated cardiomyopathy.

The cardiac T-box transcription factor TBX5 is crucial for proper cardiovascular development, and mutations in TBX5 have been associated with various congenital heart diseases and arrhythmias in humans. However, whether mutated TBX5 contributes to dilated cardiomyopathy (DCM) remains unclear. In this study, the coding exons and flanking introns of the TBX5 gene were sequenced in 190 unrelated patients with idiopathic DCM. The available family members of the index patient carrying an identified mutation and 200 unrelated ethnically matched healthy individuals used as controls were genotyped for TBX5. The functional characteristics of the mutant TBX5 were explored in contrast to its wild-type counterpart by using a dual-luciferase reporter assay system. As a result, a novel heterozygous TBX5 mutation, p.S154A, was identified in a family with DCM inherited in an autosomal dominant pattern, which co-segregated with DCM in the family with complete penetrance. The missense mutation was absent in 400 control chromosomes and the altered amino acid was completely conserved evolutionarily across various species. Functional assays revealed that the mutant TBX5 had significantly decreased transcriptional activity. Furthermore, the mutation markedly diminished the synergistic activation of TBX5 with NKX2-5 or GATA4, other two transcription factors causatively linked to DCM. This study firstly associates TBX5 loss-of-function mutation with enhanced susceptibility to DCM, providing novel insight into the molecular mechanisms of DCM, and suggesting the potential implications in the development of new treatment strategies for this common form of myocardial disorder.

A comparison of 2 devices for radial artery hemostasis after transradial coronary intervention.

BACKGROUND AND OBJECTIVE: Transradial access is an attractive approach for angiography or percutaneous coronary intervention. Different devices have been used to apply pressure locally at the site of arterial entry for achieving hemostasis. The aim of this study was to evaluate the effect of 2 different hemostatic devices on radial artery outcomes after transradial coronary intervention. SUBJECTS AND METHODS: This study included 600 patients who had undergone transradial coronary intervention who were randomized into 2 groups after the procedure: 300 were treated with a radial compression device (TR Band, Terumo Medical, Tokyo, Japan) (CD group) and the other 300 patients were treated using a chitosan-based pad (Anscare, Daxon, Taoyuan, Taiwan) (CS group). Compression time, major and minor access site bleeding complications, and incidence of radial artery occlusion were recorded. RESULTS: There were no statistical differences in the baseline clinical characteristics of the patients between the 2 groups. Compression time in the CS group was significantly shorter than that in the CD group (P < .001). Although no major access site bleeding complications were observed in either group, 6 patients in each group experienced minor access site bleeding complications. At the same time, 61 patients in the CD group and 21 patients in the CS group experienced errhysis (20% vs 7%, respectively; P < .001). Early radial artery occlusion (24 hours) occurred in 11.7% of the patients in the CD group and 5.4% of the patients in the CS group (P < .05). Chronic radial artery occlusion (30 days) occurred in 10% of the patients in the CD group and 5% of the patients in the CS group (P < .05). CONCLUSION: The application of the chitosan-based pad showed better hemostatic efficacy and a lower incidence of radial artery occlusion after transradial coronary intervention compared with the compression device.

Ginkgo biloba extract reducing myocardium cells apoptosis by regulating apoptotic related proteins expression in myocardium tissues.

The Bax, cyt-c and caspase-3 proteins play an important role in regulating the myocardial apoptosis. Although very little is known about the specific signal pathways modulated by Ginkgo biloba extract (GBE), it seems advisable to suppose that GBE-induced antiapoptotic effect might be attributed to the regulation of the expression of these proteins. Our aim was to investigate whether GBE could attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential mechanisms. In the myocardium ischemia reperfusion (IR) rat model, treatment of GBE (400 mg/kg) significantly decreased the cardiomyocyte cell apoptosis and myocardium infarction. Immunohistochemical analysis showed that GBE significantly inhibited I/R-induced increase of myocardial Bax, caspase-3, and cyt-c proteins expression. Western blot analysis confirmed results of immunohistochemical analysis. It is most likely that multiple pathways are involved in IR-induced apoptosis in rat myocardium cells. Therefore, these results demonstrate that GBE exhibits significant protective effect against myocardial I/R injury in rat heart, which is related to down-regulate Bax, cyt-c and caspase-3. Bcl-2 overexpression might prevent IR-induced apoptosis by inhibiting cytochrome c release from the mitochondria and block activation of caspase-3.

Identification of a Hippocampus-to-Zona Incerta Projection involved in Motor Learning.

Motor learning (ML), which plays a fundamental role in growth and physical rehabilitation, involves different stages of learning and memory processes through different brain regions. However, the neural mechanisms that underlie ML are not sufficiently understood. Here, a previously unreported neuronal projection from the dorsal hippocampus (dHPC) to the zona incerta (ZI) involved in the regulation of ML behaviors is identified. Using recombinant adeno-associated virus, the projections to the ZI are surprisingly identified as originating from the dorsal dentate gyrus (DG) and CA1 subregions of the dHPC. Furthermore, projection-specific chemogenetic and optogenetic manipulation reveals that the projections from the dorsal CA1 to the ZI play key roles in the acquisition and consolidation of ML behaviors, whereas the projections from the dorsal DG to the ZI mediate the retrieval/retention of ML behaviors. The results reveal new projections from the dorsal DG and dorsal CA1 to the ZI involved in the regulation of ML and provide insight into the stages over which this regulation occurs.

The protective effects of 6-CySeCD with GPx activity against UVB-induced injury in HaCaT cells.

BACKGROUND: The generation of harmful reactive oxygen species (ROS) induced by UVB irradiation could induce cell apoptosis and change the cell cycle. 6A,6A'-dicyclohexylamine-6B,6B'-diselenide-bis-ß-cyclodextrin (6-CySeCD) is a novel glutathione peroxidase (GPx; EC 1.11.1.9) mimic. The aim of this study was to investigate the anti-oxidative effects of 6-CySeCD in cultured immortalised human keratinocyte cells (HaCaT). METHODS: HaCaT cells were treated with 30 mJ/cm(2) UVB to establish a damage model. The cultured HaCaT cells were randomly assigned to the control, UVB and treatment groups. The treatment group was incubated with 20 µmol/L of GPx mimics before UVB irradiation. Cell viability was detected by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the level of lipid peroxidation was determined by the formation of malondialdehyde (MDA), DNA fragmentation was observed using agarose gel electrophoresis and the levels of intracellular ROS and cell cycle progression were measured by flow cytometry. RESULTS: The levels of cytotoxicity, intracellular ROS, lipid peroxidation and oxidative DNA damage significantly increased after UVB irradiation in the HaCaT cells. UVB irradiation caused pre-G1 -phase arrest in HaCaT cells and significantly reduced the number of HaCaT cells in the S phase. The GPx mimics 6-CySeCD and 2-phenyl-l,2-benzisoselenazol-3(2H)-one (ebselen) significantly blocked UVB-induced apoptosis and changed the cell cycle of the HaCaT cells. The blocked effect of pretreatment 6-CySeCD in UVB-irradiated HaCaT cells was better than that of pretreatment with ebselen. CONCLUSION: 6-CySeCD can relieve the damage induced by UVB irradiation in HaCaT cells.

[Peroxisome proliferator-activated receptor α/γ agonist tesaglitazar stabilizes atherosclerotic plaque in diabetic low density lipoprotein receptor knockout mice].

OBJECTIVE: To investigate the effects of peroxisome proliferator-activated receptor (PPAR) α/γ agonist on atherosclerotic plaque stabilization in diabetic LDL receptor knockout (LDLr-/-) mice. METHODS: Female 4-week-old LDLr-/- mice fed with high-glucose and high-fat diet for 4 weeks were randomly divided into three groups (n = 15 each): control group (only fed with high-glucose and high-fat diet), diabetic group [induced by high-glucose and high-fat diet combined with a low-dose of streptozotocin (STZ)] without tesaglitazar and with tesaglitazar (20 µg/kg oral treatment). After 6 weeks, the mice were sacrificed, body weight, fasting blood glucose (Glu), total cholesterol (TC), triglyceride (TG) levels were measured. The expression of ICAM-1, VCAM-1, MCP-1 in the brachiocephalic atherosclerotic lesions were determined by Western blot and immunohistochemistry, respectively. Brachiocephalic artery was prepared for morphologic study (HE, oil red O, Sirius red staining) and immunohistochemical analysis (macrophage surface molecule-3, α-smooth muscle actin), respectively. RESULTS: Serum TC [(32.34 ± 3.26) mmol/L vs. (16.17 ± 1.91) mmol/L], TG [(3.57 ± 0.99) mmol/L vs. (2.21 ± 0.11) mmol/L] and Glu [(15.21 ± 4.67) mmol/L vs. (6.89 ± 0.83) mmol/L] levels were significantly higher in diabetic group than in the control group (all P < 0.01). The expression of ICAM-1 (2.31 ± 0.35 vs.1.34 ± 0.21), VCAM-1 (1.65 ± 0.14 vs.0.82 ± 0.26), MCP-1 (2.27 ± 0.16 vs.1.56 ± 0.23) were significantly upregulated in diabetic group compared with control group (all P < 0.01). Brachiocephalic atherosclerotic plaque area [(4.597 ± 1.260)×10(3) µm(2) vs. (0.075 ± 0.030)×10(3) µm(2)], lipid deposition [(47.23 ± 2.64)% vs. (9.67 ± 1.75)%], Mac-3 positive area [(19.15 ± 3.51)% vs. (1.72 ± 0.16)%], α-smooth muscle actin [(5.54 ± 1.17)% vs. (2.13 ± 0.41)%] and collagen content [(4.27 ± 0.74)% vs. (0.43 ± 0.09)%] were all significantly larger/higher in diabetic LDLr-/- mice than in the control group (all P < 0.01). While tesaglitazar treatment significantly reduced serum TC [(30.47 ± 3.18) mmol/L], TG [(3.14 ± 0.71) mmol/L] and Glu [(7.92 ± 1.28) mmol/L] levels (all P < 0.01). Similarly, the expression of ICAM-1 [(1.84 ± 0.22)], VCAM-1 [(1.27 ± 0.11)], MCP-1 [(1.83 ± 0.24)], brachiocephalic atherosclerotic lesion area[(1.283 ± 0.410)×10(3) µm(2)], lipid deposition[(23.52 ± 1.39)%] were also significantly reduced by tesaglitazar (all P < 0.05). Moreover, tesaglitazar increased α-smooth muscle actin [(9.46 ± 1.47)%] and collagen content [(6.32 ± 1.15)%] in diabetic LDLr-/- mice (all P < 0.05). In addition, lipid deposition and Mac-3 positive areas [(10.67 ± 0.88)% vs. (15.83 ± 1.01)%] in the aortic root were also reduced in tesaglitazar treated diabetic LDLr-/- mice (P < 0.01). CONCLUSIONS: Tesaglitazar has anti-inflammatory effects in the diabetic LDLr-/- mice. Tesaglitazar could reduce lipid deposition, increase collagen and α-SMA content in the brachiocephalic atherosclerotic lesions, thus, stabilize atherosclerotic plaque in this model.

A meta-analysis of the association of adiponectin gene polymorphisms with coronary heart disease in Chinese Han population.

OBJECTIVE: Variants of adiponectin gene have been reported to be associated with coronary heart disease (CHD), but the available data on this relationship are inconsistent. A meta-analysis was performed to quantitatively analyse the association of adiponectin gene polymorphisms with coronary artery disease using previous case-control studies in Chinese Han populations. METHODS: Several electronic databases were searched for relevant articles up to January 2011. After data collection and gene loci selection, a meta-analysis was performed to assess heterogeneity, combine results and evaluate variations. Publication bias was examined by the Egger's linear regression test. Hardy-Weinberg equilibrium (HWE) test and by omitting one study at a time was employed for the sensitivity analysis. RESULTS: Eleven studies covering 4303 subjects focusing on two polymorphisms [+45T→G (rs2241766) and +276G→T (rs1501299)] in the adiponectin gene and risk of CHD were included in the meta-analysis. Combined analyses of studies of the SNP+45 showed no significant overall association with CHD, yielding ORs of 1·03 (0·80, 1·34) and 1·32 (0·86, 2·03) under a dominant and recessive model, respectively, with strong evidence of heterogeneity. Similar results were also obtained in other genetic models. Concerning SNP+276, a significantly decreased CHD risk was observed under a dominant model, a codominant model and a allele contrast model, with an odds ratio of 0·67 (0·54, 0·83), 0·77 (0·62, 0·94) and 0·69 (0·55, 0·86), respectively. Sensitivity analysis confirmed the reliability and stability of this meta-analysis. CONCLUSIONS: The accumulated evidence suggested that the adiponectin gene polymorphism, SNP+45, is not associated with CHD, but the SNP+276T allele might be associated with decreased risk of CHD in the Chinese Han population. More well-designed large studies are required for the validation of this association.

Serum total adiponectin level and risk of cardiovascular disease in Han Chinese populations: a meta-analysis of 17 case-control studies.

OBJECTIVE: To systematically evaluate low serum adiponectin level as a risk factor for cardiovascular disease (CVD). A meta-analysis was performed to quantitatively analyse the association of serum total adiponectin level with CVD using previous case-control studies in Han Chinese populations. METHODS: Several electronic databases were searched for relevant articles up to July 2011. A total of nine (n = 933), eight (n = 939) articles were included in each meta-analysis regarding the association of serum adiponectin level with coronary heart disease (CHD) and ischaemic stroke, respectively. Publication bias was examined by the Egger's linear regression test. Sensitivity analysis was performed by omitting one study at a time, and the pooled standardized mean difference (SMD) was estimated using fixed-effects model and random-effects model, respectively. RESULTS: Serum total adiponectin concentrations were lower in patients with CHD and ischaemic stroke, with pooled SMD of -1·41 (95% CI -1·69, -1·12, P < 0·00001) and -1·69 (95% CI -2·04, -1·33, P < 0·00001), respectively. By performing a meta-regression analysis, homeostasis model assessment of insulin resistance, study size, adiponectin measurement assays, gender and mean body mass index of cases failed to account for heterogeneity for comparisons between lower adiponectin level and ischaemic stroke. However, study size had significant effect on the association of lower adiponectin level with CHD and accounted for 96·72% of the between-study variance. No publication bias was detected. No single study was found to affect the overall result of each analysis by sensitivity testing. CONCLUSIONS: The accumulated evidence suggested that low serum adiponectin level increased the risk of a first cardiovascular event in the Han Chinese population. Further study is recommended with larger sample size to explore the role of hypoadiponectinemia in the causation of CVD.

Salidroside decreases atherosclerotic plaque formation in low-density lipoprotein receptor-deficient mice.

Salidroside is isolated from Rhodiola rosea and is one of the main active components in Rhodiola species. The present study was designed to evaluate the effects of Salidroside on atherosclerotic plaque formation in high-fat diet-(HFD-) fed female LDL receptor knockout (LDLr(-/-)) mice. LDLr(-/-) mice fed an atherogenic HFD for 12 weeks were divided into two groups. One group was administered Salidroside (50 mg/kg/oral gavage) daily for 8 weeks, while the control group was administered saline. Salidroside treatment reduced serum lipids levels and the plaque area through the arch to the abdominal aorta. Furthermore, Salidroside improved macrophage content and enhanced collagen and smooth muscle cells contents in the aortic sinus. These changes were associated with reduced MCP-1, VCAM-1, and VCAM-1 protein expression in atherosclerotic aortas. All these results suggest that Salidroside decreases atherosclerotic plaques formation via effects on lipid lowering and anti-inflammation in HFD-fed LDLr(-/-) mice.

Increased serum myeloid-related protein 8/14 level is associated with atherosclerosis in type 2 diabetic patients.

BACKGROUND: Myeloid-related protein 8/14 (MRP8/14) is a stable heterodimer formed by two different calcium-binding proteins (MRP8 and MRP14). Studies have identified that MRP8/14 regulates vascular inflammation and serves as a novel marker of acute coronary syndrome. In this study, we evaluated the correlation between serum levels of MRP8/14, hsCRP, endogenous secretory receptor for advanced glycation end-products (esRAGE) and the occurrence of coronary artery disease (CAD), or carotid intima-media thickness (IMT) when CAD was not yet developed in diabetic patients. METHODS: Serum levels of MRP8/14, esRAGE and hsCRP were measured in 375 diabetic patients. Then the results of those who had CAD were compared against who had not. Also, we investigated the associations between above-mentioned indicators and IMT of subjects without CAD in both diabetic group and non-diabetic one. RESULTS: Serum MRP8/14 was significantly higher in CAD than in non-CAD group (9.7 ± 3.6 ug/ml vs. 8.2 ± 3.0 ug/ml, P < 0.001). It was associated with severity of CAD (r = 0.16, P = 0.026). In non-CAD group, MRP8/14 was associated with IMT in patients with (r = 0.30, P < 0.001) or without diabetes (r = 0.26, P = 0.015). The areas under the curves of receiver operating characteristic for CAD were 0.63 (95% CI 0.57-0.68) for MRP8/14, 0.76 (95% CI 0.71-0.81) for hsCRP and 0.62 (95% CI 0.56 -0.67) for esRAGE. CONCLUSION: In summary, we report that diabetic patients with CAD had elevated plasma MRP8/14 levels which were also positively correlated with the severity of CAD and carotid IMT in patients without clinically overt CAD.

Vaspin plasma concentrations and mRNA expressions in patients with stable and unstable angina pectoris.

BACKGROUND: Vaspin was a recently identified adipokine, playing a protective role in many metabolic diseases. The present study aimed to investigate the association between vaspin plasma level and stable angina pectoris (SAP) and unstable angina pectoris (UAP). METHODS: A total of 88 patients with angiographically-proved coronary artery disease (CAD) (SAP 47, UAP 41) and 103 control subjects without cardiovascular diseases were enrolled in this study. Circulating vaspin, mRNA expression of vaspin in peripheral blood mononuclear cells (PBMC), clinical parameters, lipid profile and high-sensitivity C-reactive protein (hsCRP) were assayed. The severity of CAD was also assessed according to the number of vessels diseased. RESULTS: There are significant differences in circulating vaspin levels and mRNA levels of PBMC between SAP and UAP groups (SAP 0.91±0.95 ng/mL and UAP 0.43±0.38 ng/mL, p<0.01 in circulating vaspin level; SAP 1.19±0.85 and UAP 0.82±0.56, p<0.05 in mRNA level of PBMC). An inverse correlation between the number of diseased vessels and plasma vaspin concentration was observed (r=-0.350, p<0.01) in the CAD group. Construction of receiver operating characteristic curves confirmed that vaspin plasma concentrations significantly differentiated CAD patients (area under the curve=0.684, p<0.001), as well as UAP (area under the curve=0.640, p<0.05). CONCLUSION: Decreased vaspin plasma levels and mRNA levels in PBMC were observed in patients with UAP. Low vaspin concentrations correlate with CAD severity. The findings suggested that vaspin could serve as a novel biomarker of CAD as well as UAP.

[A meta-analysis of early percutaneous coronary intervention within 24 hours of thrombolysis in acute ST-elevation myocardial infarction].

OBJECTIVE: To evaluate the efficacy and safety of early percutaneous coronary intervention (PCI) within 24 hours of thrombolysis in acute ST-elevation myocardial infarction. METHODS: The databases of Medline, EMBASE, Elsevier, Cochrane library, Wanfang and CNKI were searched for randomized controlled trials. Quality assessment and data extraction were performed by two independent reviewers. Statistical analyses were conducted with Stata 10.0 and RevMan 5.0 software. RESULTS: Eight studies (NORDI-STEMI, TRANSFER-AMI, WEST, CARESS-AMI, CAPITAL-AMI, GRACIA-I, SIAMI III & PRAGUE-I) involving a total of 3157 patients fulfilled the inclusion criteria. Meta-analysis results showed that, as compared with the control group, (1) the combined endpoint of 30 day mortality, re-infarction and ischemia was significantly lower in early PCI within 24 h of thrombolysis group [relative risk (RR) = 0.52, 95% confidence interval (CI) 0.42 - 0.65, P < 0.001]; (2) 30-day re-infarction decreased in early PCI within 24 h of thrombolysis group (RR = 0.57, 95%CI 0.40 - 0.81, P = 0.002); (3) 30-day ischemia had a significant reduction in early PCI within 24 h of thrombolysis group (RR = 0.27, 95%CI 0.14 - 0.52, P < 0.001); (4) 30-day major hemorrhage or mortality rates were not significantly different between two groups (RR = 1.07, 95%CI 0.78-1.46, P = 0.69; RR = 0.86, 95%CI 0.62 - 1.20, P = 0.38 respectively). CONCLUSION: When primary PCI is not feasible, our meta-analysis favors early PCI within 24 h of thrombolysis for acute ST-elevation myocardial infarction. Early PCI is associated with a lowered recurrence of major adverse cardiac events, ischemia and re-infarction. But there is no elevated risk of major hemorrhage and mortality.