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.

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.

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.

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.

Expression of a short antibody heavy chain peptide effectively antagonizes adenosine 2A receptor in vitro and in vivo.

BACKGROUND: Adenosine 2A receptor (A2AR) is involved in many physiological and pathological functions and serves as an important drug target. Inhibition of A2AR may alleviate symptoms associated with a variety of neuropsychiatric disorders. However, the currently used A2AR antagonists have specificity limitations. RESEARCH DESIGN AND METHODS: A Fab fragment (Fab2838) of an A2AR mouse monoclonal antibody can specifically bind to A2AR to form a complex and inhibit the activity of its receptor. We constructed the vector AntiA2AR, a small-molecule peptide that binds to and inhibits A2AR based on Fab2838. RESULTS: Experiments in HEK293T cells showed that peptide AntiA2AR of 29 peptides was the most effective among the synthesized peptides in inhibiting the A2AR downstream signal cAMP/PKA/CREB. In neurons, the AntiA2AR reversed the calcium flow change induced by the A2AR agonist CGS21680 (1 µM). Furthermore, AntiA2AR expression in the mice striatum weakened the p-PKA/p-CREB signal, enhanced locomotor abilities and increased time spent in the center area in the home-cage observation experiment and increased anxiolytic behavior in the elevated-plus maze test. CONCLUSIONS: Antagonistic peptide AntiA2AR can effectively block the A2AR signaling pathway. This provides a new strategy for the specific inhibition of A2AR and provides information needed for drug development.

CTRP5-Overexpression Attenuated Ischemia-Reperfusion Associated Heart Injuries and Improved Infarction Induced Heart Failure.

Aims: C1q/tumor necrosis factor (TNF)-related protein 5 (CTRP5) belongs to the C1q/TNF-α related protein family and regulates glucose, lipid metabolism, and inflammation production. However, the roles of CTRP5 in ischemia/reperfusion (I/R) associated with cardiac injuries and heart failure (HF) needs to be elaborated. This study aimed to investigate the roles of CTRP5 in I/R associated cardiac injuries and heart failure. Materials and Methods: Adeno-associated virus serum type 9 （AAV9）vectors were established for CTRP5 overexpression in a mouse heart (AAV9-CTRP5 mouse). AAV9-CTRP5, AMPKα2 global knock out （AMPKα2-/-）and AAV9-CTRP5+ AMPKα2-/- mice were used to establish cardiac I/R or infarction associated HF models to investigate the roles and mechanisms of CTRP5 in vivo. Isolated neonatal rat cardiomyocytes (NRCMS) transfected with or without CTRP5 adenovirus were used to establish a hypoxia/reoxygenation (H/O) model to study the roles and mechanisms of CTRP5 in vitro. Key Findings: CTRP5 was up-regulated after MI but was quickly down-regulated. CTRP5 overexpression significantly decreased I/R induced IA/AAR and cardiomyocyte apoptosis, and attenuated infarction area, and improved cardiac functions. Mechanistically, CTRP5 overexpression markedly increased AMPKα2 and ACC phosphorylation and PGC1-α expression but inhibited mTORC1 phosphorylation. In in vitro experiments, CTRP5 overexpression could also enhance AMPKα2 and ACC phosphorylation and protect against H/O induced cardiomyocytes apoptosis. Finally, we showed that CTPR5 overexpression could not protect against I/R associated cardiac injuries and HF in AMPKα2-/- mice. Significance: CTRP5 overexpression protected against I/R induced mouse cardiac injuries and attenuated myocardial infarction induced cardiac dysfunction by activating the AMPKαsignaling pathway.

Exosomes Derived from TIMP2-Modified Human Umbilical Cord Mesenchymal Stem Cells Enhance the Repair Effect in Rat Model with Myocardial Infarction Possibly by the Akt/Sfrp2 Pathway.

Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) are a promising new therapeutic option for myocardial infarction (MI). The tissue matrix metalloproteinase inhibitor 2, also known as TIMP2, is a member of the tissue inhibitor family of metalloproteinases. Since TIMP2-mediated inhibition of matrix metalloproteinases (MMPs) is a key determinant of post-MI remodeling, we analyzed the therapeutic effects of exosomes derived from TIMP2-overexpressing hucMSCs (huc-exoTIMP2) on the MI rat model. The huc-exoTIMP2 significantly improved in vivo cardiac function as measured by echocardiography and promoted angiogenesis in MI injury. It also restricted extracellular matrix (ECM) remodeling, as indicated by the reduced collagen deposition. In addition, huc-exoTIMP2 administration increased the in situ expression of the antiapoptotic Bcl-2 and decreased that of the proapoptotic Bax and pro-caspase-9 in the infracted myocardium. Meanwhile, huc-exoTIMP2 upregulated superoxide dismutase (SOD) as well as glutathione (GSH) and decreased the malondialdehyde (MDA) level in MI models. In vitro huc-exoTIMP2 pretreatment could inhibit H2O2-mediated H9C2-cardiomyocyte apoptosis and promote human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation, as well as decrease TGFß-induced MMP2, MMP9, and α-SMA secretion by cardiac fibroblasts (CFs). Besides that, huc-exoTIMP2 pretreatment also increased the expression of Akt phosphorylation in the infarcted myocardium, which may relate to a high level of secreted frizzled-related protein 2 (Sfrp2) in huc-exoTIMP2, indicating a mechanistic basis of its action. Importantly, Sfrp2 knockdown in huc-exoTIMP2 abrogated the protective effects. Taken together, huc-exoTIMP2 improved cardiac function by alleviating MI-induced oxidative stress and ECM remodeling, partly via the Akt/Sfrp2 pathway.

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.

Translocase of Inner Membrane 50 Functions as a Novel Protective Regulator of Pathological Cardiac Hypertrophy.

BACKGROUND: Translocase of inner membrane 50 (TIM50) is a member of the translocase of inner membrane (TIM) complex in the mitochondria. Previous research has demonstrated the role of TIM50 in the regulation of oxidative stress and cardiac morphology. However, the role of TIM50 in pathological cardiac hypertrophy remains unknown. METHODS AND RESULTS: In the present study we found that the expression of TIM50 was downregulated in hypertrophic hearts. Using genetic loss-of-function animal models, we demonstrated that TIM50 deficiency increased heart and cardiomyocyte size with more severe cardiac fibrosis compared with wild-type littermates. Moreover, we generated cardiomyocyte-specific TIM50 transgenic mice in which the hypertrophic and fibrotic phenotypes were all alleviated. Next, we tested reactive oxygen species generation and the activities of the antioxidant enzymes superoxide dismutase and catalase, and also respiratory chain complexes I, II, and IV, finding that all the activities were regulated by TIM50. Meanwhile, expression of the ASK1-JNK/P38 axis was increased in TIM50-deficient mice, and TIM50 overexpression decreased the activity of the ASK1-JNK/P38 axis. Finally, we treated mice with the antioxidant N-acetyl cysteine to reduce oxidative stress. After N-acetyl cysteine treatment, the deteriorative hypertrophic and fibrotic phenotypes caused by TIM50 deficiency were all remarkably reversed. CONCLUSIONS: These data indicated that TIM50 could attenuate pathological cardiac hypertrophy primarily by reducing oxidative stress. TIM50 could be a promising target for the prevention and therapy of cardiac hypertrophy and heart failure.

Eupatilin inhibits the apoptosis in H9c2 cardiomyocytes via the Akt/GSK-3ß pathway following hypoxia/reoxygenation injury.

Eupatilin, a pharmacologically active flavone derived from the Artemisia plant species, has been reported to have anti-oxidant, anti-inflammatory, anti-allergic, and neuroprotective activities against cerebral ischemia/reperfusion (I/R). However, the role of eupatilin in myocardial I/R injury remains unclear. In the present study, we aimed to investigate the potential molecular mechanisms against hypoxia/reoxygenation (H/R) induced cardiomyocytes apoptosis in vitro. Our results showed that eupatilin markedly improved the cell viability and decreased lactate dehydrogenase (LDH) release. Eupatilin also suppressed oxidative stress and apoptosis in H9c2 cells after myocardial I/R injury. Furthermore, eupatilin obviously increased the phosphorylation of Akt and GSK-3ß in H9c2 cells. Our results suggested that eupatilin could provide significant cardioprotection against myocardial I/R injury, and the potential mechanisms might involve inhibition of cardiomyocyte apoptosis through activating the Akt/GSK-3ß signaling pathway.

Renoprotective effect of alprostadil in combination with statins in patients with mild to moderate renal failure undergoing coronary angiography.

BACKGROUND: The role of alprostadil and statins in contrast-induced acute kidney injury (CI-AKI) is controversial. The purpose of this study was to explore the efficacy of combined therapy with alprostadil and statins in protecting renal function and preventing contrast-induced nephropathy (CIN) in patients undergoing coronary angiography. METHODS: A total of 156 consecutive patients with mild to moderate renal failure who underwent coronary angiography were enrolled in our study, and randomly categorized into two groups. In the statins group, 80 patients were treated with statins before and after coronary angiography. In the alprostadil plus statins group, 76 patients were treated with statins and alprostadil before and after coronary angiography. Serum creatinine (SCr), serum cystatin (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) were detected after administration of contrast media, and adverse events were evaluated within six months. RESULTS: In both groups, the SCr, CysC and NGAL significantly increased after coronary angiography and peaked at 48, 24 and 6 hours, respectively. SCr, CysC and NGAL were significantly lower in the alprostadil plus statins group than in the statins group (P < 0.05). The incidence of CIN in the alprostadil plus statins group was slightly lower than in the statins group. The incidence of adverse events within six months in the alprostadil plus statins group was significantly lower than in the statins group (P = 0.034). CONCLUSIONS: Intravenous alprostadil in combination with oral statins is superior to statins alone for protecting renal function in patients with mild to moderate renal dysfunction who undergo coronary angiography, and can reduce the incidence of adverse events seen within six months.

Comparison of double kissing crush versus Culotte stenting for unprotected distal left main bifurcation lesions: results from a multicenter, randomized, prospective DKCRUSH-III study.

OBJECTIVES: The study aimed to investigate the difference in major adverse cardiac event (MACE) at 1-year after double kissing (DK) crush versus Culotte stenting for unprotected left main coronary artery (UPLMCA) distal bifurcation lesions. BACKGROUND: DK crush and Culotte stenting were reported to be effective for treatment of coronary bifurcation lesions. However, their comparative performance in UPLMCA bifurcation lesions is not known. METHODS: A total of 419 patients with UPLMCA bifurcation lesions were randomly assigned to DK (n = 210) or Culotte (n = 209) treatment. The primary endpoint was the occurrence of a MACE at 1 year, including cardiac death, myocardial infarction, and target vessel revascularization (TVR). In-stent restenosis (ISR) at 8 months was secondary endpoint, and stent thrombosis (ST) served as a safety endpoint. Patients were stratified by SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) and NERS (New Risk Stratification) scores. RESULTS: Patients in the Culotte group had significant higher 1-year MACE rate (16.3%), mainly driven by increased TVR (11.0%), compared with the DK group (6.2% and 4.3%, respectively; all p < 0.05). ISR rate in side branch was 12.6% in the Culotte group and 6.8% in the DK group (p = 0.037). Definite ST rate was 1.0% in the Culotte group and 0% in the DK group (p = 0.248). Among patients with bifurcation angle ≥70°, NERS score ≥20, and SYNTAX score ≥23, the 1-year MACE rate in the DK group (3.8%, 9.2%, and 7.1%, respectively) was significantly different to those in the Culotte group(16.5%, 20.4%, and 18.9%, respectively; all p < 0.05). CONCLUSIONS: Culotte stenting for UPLMCA bifurcation lesions was associated with significantly increased MACEs, mainly due to the increased TVR. (Double Kissing [DK] Crush Versus Culotte Stenting for the Treatment of Unprotected Distal Left Main Bifurcation Lesions: DKCRUSH-III, a Multicenter Randomized Study Comparing Double-Stent Techniques; ChiCTR-TRC-00000151).

Long-term efficacy of transcatheter closure of ventricular septal defect in combination with percutaneous coronary intervention in patients with ventricular septal defect complicating acute myocardial infarction: a multicentre study.

AIMS: To assess the immediate and long-term outcomes of transcatheter closure of ventricular septal defect (VSD) in combination with percutaneous coronary intervention (PCI) in patients with VSD complicating acute myocardial infarction (AMI). METHODS AND RESULTS: Data were prospectively collected from 35 AMI patients who underwent attempted transcatheter VSD closure and PCI therapy in five high-volume heart centres. All the patients who survived the procedures were followed up by chest x-ray, electrocardiogram and echocardiography. Thirteen patients underwent urgent VSD closure in the acute phase (within two weeks from VSD) while the others underwent elective closure at a median of 23 days from VSD occurrence. The percentage of VSD closure device success was 92.3% (36/39) and procedure success was 91.4% (32/35). The incidence of in-hospital mortality was 14.3% (5/35). At a median of 53 months follow-up, only two patients died at 38 and 41 months, respectively, and other patients' cardiac function tested by echocardiography improved significantly compared to that evaluated before discharge. CONCLUSION: The combination of transcatheter VSD closure and PCI for treating VSD complicating AMI is safe and feasible and is a promising alternative to surgery in patients with anatomically suitable VSD and coronary lesion.

High-dose statin pretreatment for the prevention of contrast-induced nephropathy: a meta-analysis.

BACKGROUND: Contrast-induced nephropathy (CIN) is a rare but serious complication following contrast-based procedures. Statins have been postulated to prevent CIN via various mechanisms. However, the outcomes following statin administration to prevent CIN have been inconsistent. METHODS: A meta-analysis of published randomized clinical trials was performed to determine if short-term administration of high-dose statin is superior to conventional-dose statin or placebo among patients undergoing catheterization and interventional procedures in preventing CIN. RESULTS: Data were combined across 8 published clinical trials in which 1423 patients were identified. Pooled analyses showed that short-term high-dose statin treatment can decrease the occurrence of CIN (risk ratio 0.51, 95% confidence interval [CI], 0.34-0.77; P=0.001) and 48-hour serum creatinine level (standardized mean difference [SMD] -0.07 mg/dL; 95% CI, -0.11 to -0.04 mg/dL; P<0.00001). However, subgroup analysis showed that statin pretreatment cannot decrease the occurrence of CIN in patients with preexisting renal impairment (RR 0.90; 95% CI, 0.49-1.65; P=0.73). No evidence of publication bias was detected. CONCLUSIONS: This meta-analysis supports the effectiveness of short-term high-dose statin pretreatment for both decreasing the level of serum creatinine and reducing the rate of CIN in patients undergoing diagnostic and interventional procedures requiring contrast media. However, prospective clinical trials will be needed to draw a definitive conclusion in this area.

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.

Dihydroxyflavonol reduces post-infarction left ventricular remodeling by preventing myocyte apoptosis in the non-infarcted zone in goats.

BACKGROUND: Myocyte apoptosis is considered to be the major causative factor of left ventricular (LV) remodeling following myocardial infarction (MI). We previously reported that 3', 4'-dihydroxyflavonol (DiOHF), was able to suppress oxidative stress and preserve the expression of endothelial nitric oxide synthase during myocardial reperfusion injury, which may benefit the reduction of myocyte apoptosis. We therefore aimed to evaluate the potential actions of DiOHF against myocyte apoptosis and post-infarction LV remodeling in this study. METHODS: Following experimental MI, surgical instrumented goats were randomly assigned into vehicle and DiOHF (2 mg/kg; i.v., daily) groups to receive 4 weeks of reperfusion with corresponding treatments. LV pressure recordings and echocardiogram were performed at baseline, 2 and 4 weeks of reperfusion. Myocardial tissues were collected in the end to determine infarct size and apoptosis related assays. RESULTS: LV end-diastolic volume and diameter were significantly increased 4 weeks after MI in the vehicle group, accompanied by reduced posterior wall thickness, septal thickness and LV mass, whereas those changes were markedly prevented by DiOHF treatment. Similarly, significantly reduced infarct size was found in DiOHF group as compared to vehicle group, and DiOHF dramatically inhibited the increase in LV end-diastolic pressure and the reductions in ejection fraction, fraction shortening and dP/dt(max). Moreover, DiOHF treatment significantly reduced the extent of myocyte apoptosis detected by TUNEL assay, enhanced the protein expression of caspase-3, Fas, Bax and cytochrome c in the non-infarcted myocardium in comparison to vehicle. CONCLUSIONS: Daily DiOHF treatment during the reperfusion period after MI in the ovine hearts markedly reduced the magnitude of post-infarction LV remodeling through the inhibition of myocyte apoptosis in the remote non-infarcted myocardium.

[Prevalence of peripheral arterial disease and correlative risk factors among natural population in China].

OBJECTIVE: To investigate the prevalence of peripheral arterial disease (PAD) and correlative risk factors among natural population in China. METHODS: Ankle brachial index (ABI) was measured by trained doctors and related data were collected in residents from Beijing, Shanghai, Changsha, Guangdong, Neimenggu, and Xinjiang selected through cluster multistage and random sampling method. PAD was defined as an ABI < or = 0.9 in either leg. RESULTS: The prevalence of PAD among 21 152 eligible participants was 3.08%, the standardized prevalence was 3.04%. The prevalence in males and females was 2.52% and 3.66% and the standardized prevalence was 1.84% and 4.31% respectively, the prevalence rate was significantly lower in males than that in females (P < 0.01). The prevalence in both males and females increased significantly in proportion to aging (P < 0.01). The prevalence in Han Chinese was significantly higher than that in non-Han Chinese (P < 0.01). Logistic regression analysis showed that older age, female gender, Han Chinese, waist circumference, smoking, lipid disorder, diabetes mellitus, coronary artery disease and a history of ischemic stroke were associated with the increased prevalence of PAD. Incidence of known PAD was 1.38% in this cohort. CONCLUSIONS: Older age, female gender, Han Chinese, waist circumference, smoking, lipid disorder, diabetes mellitus, coronary artery disease and a history of ischemic stroke were associated with the increased prevalence of PAD in natural Chinese population.