Genome sequences and population genomics reveal climatic adaptation and genomic divergence between two closely related sweetgum species.

Understanding the genetic basis of population divergence and adaptation is an important goal in population genetics and evolutionary biology. However, the relative roles of demographic history, gene flow, and/or selective regime in driving genomic divergence, climatic adaptation, and speciation in non-model tree species are not yet fully understood. To address this issue, we generated whole-genome resequencing data of Liquidambar formosana and L. acalycina, which are broadly sympatric but altitudinally segregated in the Tertiary relict forests of subtropical China. We integrated genomic and environmental data to investigate the demographic history, genomic divergence, and climatic adaptation of these two sister species. We inferred a scenario of allopatric species divergence during the late Miocene, followed by secondary contact during the Holocene. We identified multiple genomic islands of elevated divergence that mainly evolved through divergence hitchhiking and recombination rate variation, likely fostered by long-term refugial isolation and recent differential introgression in low-recombination genomic regions. We also found some candidate genes with divergent selection signatures potentially involved in climatic adaptation and reproductive isolation. Our results contribute to a better understanding of how late Tertiary/Quaternary climatic change influenced speciation, genomic divergence, climatic adaptation, and introgressive hybridization in East Asia's Tertiary relict flora. In addition, they should facilitate future evolutionary, conservation genomics, and molecular breeding studies in Liquidambar, a genus of important medicinal and ornamental values.

Role of miR-211 in a PC12 cell model of Alzheimer's disease via regulation of neurogenin 2.

NEW FINDINGS: What is the central question of this study? What is the mechanism of miR-211 in an Alzheimer's disease cell model? What is the main finding and its importance? miR-211 was upregulated in an Alzheimer's disease cell model. It targeted neurogenin 2, reduced the activation of the phosphoinositide 3-kinase-Akt signalling pathway, inhibited the proliferation of the Alzheimer's disease cell model and promoted apoptosis. ABSTRACT: MicroRNAs (miRs) are aberrantly expressed in Alzheimer's disease (AD) patients. This study was intended to investigate the effect of miR-211 on an AD cell model and the involvement of neurogenin 2 (Ngn2). The appropriate dose and time for the effect of Aß1-42 on PC12 cells were determined to establish an AD cell model. An effect of miR-211 expression on cell viability, proliferation and apoptosis was detected after cell transfection. Online prediction and a dual luciferase reporter gene assay were utilized to confirm the binding sequence of miR-211 and Ngn2. qRT-PCR and western blot analysis were applied to measure Ngn2 expression. A gain and loss of function assay of miR-211 and Ngn2 was performed, and activation of the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway was detected. The AD cell model was induced by Aß1-42 treatment. miR-211 expression was significantly enhanced after miR-211 transfection, leading to suppressed proliferation and promotion of apoptosis in Aß1-42 -treated PC12 cells. In addition, miR-211 could downregulate Ngn2 mRNA and protein expression, while overexpression of Ngn2 could reverse the effects of miR-211 on Aß1-42 -treated PC12 cells and significantly enhance the phosphorylated Akt and PI3K protein levels. miR-211 could inhibit growth of PC12 cells by suppressing Ngn2 expression and inactivating the PI3K-Akt signalling pathway.

Paeoniflorin attenuates early brain injury through reducing oxidative stress and neuronal apoptosis after subarachnoid hemorrhage in rats.

Paeoniflorin is a natural monoterpene glucoside from Paeoniae Radix with neuroprotective properties. However, it is still unclear whether paeoniflorin has neuroprotective effects on subarachnoid hemorrhage (SAH). This study explores the effect of paeoniflorin on early brain injury (EBI) using rat SAH model. We found that paeoniflorin significantly improves neurological deficits, attenuates brain water content and Evans blue extravasation at 72 h after SAH. Paeoniflorin attenuates the oxidative stress following SAH as evidenced by decrease of reactive oxygen species (ROS), malondialdehyde (MDA), 3-Nitrotyrosine, and 8-Hydroxy-2-deoxy guanosine (8-OHDG) level, increase of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase activity, and up-regulates the nuclear factor erythroid­related factor 2 (Nrf2)/heme oxygenase­1 (HO-1) pathway. Inhibition of microglia activation and neuro-inflammatory response both contributed to paeoniflorin's protective effects. Moreover, paeoniflorin treatment significantly reduces the ratio of Bax/Bcl-2, active caspase-3/ neuronal nuclei (NeuN) and TUNEL/DAPI positive cells at 72 h following SAH. Our results indicate that paeoniflorin may attenuate early brain injury after experimental SAH.

Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway.

AIM: Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. METHODS: Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg(-1)·d(-1), po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins. RESULTS: DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine. CONCLUSION: Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway.

Effect of Thrombolysis on Circulating Microparticles in Patients with ST-Segment Elevation Myocardial Infarction.

Objective: We demonstrated that circulating microparticles (MPs) are increased in patients with coronary heart disease (both chronic coronary syndrome (CCS) and acute coronary syndrome). Whether thrombolysis affects MPs in patients with ST-segment elevation myocardial infarction (STEMI) with or without percutaneous coronary intervention (PCI) is unknown. Methods: This study was divided into three groups: STEMI patients with thrombolysis (n = 18) were group T, patients with chronic coronary syndrome (n = 20) were group CCS, and healthy volunteers (n = 20) were the control group. Fasting venous blood was extracted from patients in the CCS and control groups, and venous blood was extracted from patients in the T group before (pre-T) and 2 hours after (post-T) thrombolysis. MPs from each group were obtained by centrifugation. After determining the concentration, the effects of MPs on endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in rat myocardial tissue in vitro were detected by immunohistochemistry and western blotting. Changes in nitric oxide (NO) and oxygen free radicals (O2•-) were also detected. The effect of MPs on vasodilation in isolated rat thoracic aortae was detected. Results: Compared with that in the control group (2.60 ± 0.38 mg/ml), the concentration of MPs was increased in patients with CCS (3.49 ± 0.72 mg/ml) and in STEMI patients before thrombolysis (4.17 ± 0.58 mg/ml). However, thrombolysis did not further increase MP levels (post-T, 4.23 ± 1.01 mg/ml) compared with those in STEMI patients before thrombolysis. Compared with those in the control group, MPs in both CCS and STEMI patients before thrombolysis inhibited the expression of eNOS (both immunohistochemistry and western blot analysis of phosphorylation at Ser1177), NO production in the isolated myocardium and vasodilation in vitro and stimulated the expression of iNOS (immunohistochemistry and western blot analysis of phosphorylation at Thr495), and the generation of O2•- in the isolated myocardium. The effects of MPs were further enhanced by MPs from STEMI patients 2 hours after thrombolysis. Conclusion: Changes in MP function after thrombolysis may be one of the mechanisms leading to ischemia-reperfusion after thrombolysis.

The Alteration of HDL in Patients with AMI Inhibited Angiogenesis by Blocking ERK1/2 Activation.

Objective: High-density lipoprotein (HDL) was found vasoprotective, but numbers of patients with acute myocardial infarction (AMI) have normal or even high levels of pathological HDL (pHDL). So, we investigate the mechanism of pHDL in AMI patients on angiogenesis. Methods: HDL with normal levels from healthy subjects (nHDL, control group, n = 20) and patients with AMI (pHDL, experimental groups, n = 30) were obtained by super high speed centrifugation. Then, effects of HDL on proliferation, migration, angiogenesis, and expression of ERK1/2 and its phosphorylation in human umbilical vein endothelial cells (HUVEC) with or without PD98059 (inhibitor of ERK1/2) preincubation were detected. Results: Compared with the control group (nHDL), HDL from the experimental group (pHDL) significantly inhibited the phosphorylation of ERK1/2, proliferation, migration, and angiogenesis of HUVEC (P < 0.05), while these effects of HDL could substantially be blocked by preincubation of PD98059 (P < 0.05). Conclusion: HDL in AMI patients affects angiogenesis by inhibiting ERK1/2 activation free from HDL levels.

[Effecacy of three-dimensional conformal radiation therapy combined with Tegafur for postoperative recurrent rectal carcinoma].

OBJECTIVE: To observe the local control rate, survival time and side effect of three-dimensional conformal radiation therapy combined with Tegafur for postoperative recurrent rectal carcinoma. METHODS: Forty patients with postoperative recurrent rectal carcinoma received three-dimensional conformal radiation therapy, 1.8 - 2.0 Gy/once, 5 times every week and the total dose was 54 - 65 Gy. At the same time, the patients took Tegafur orally 40 mg/m(2) twice per day for consecutive 28 days, and one cycle lasted for 42 days. The chemotherapy was applied for 2 cycles after radiotherapy. RESULTS: The total effective rate (CR + PR) was 70.0%, improvement rate was 90.0%, 1-year survival rate was 70.0%, and 1-year local control rate was 62.5%. There was only a little side effect. CONCLUSIONS: Three-dimensional conformal radiation therapy combined with Tegafur for postoperative recurrent rectal carcinoma have definite effect, with a high local control rate, and patients well tolerance the treatment without serious side effect. It can apparently improve the life quality of the patients.

Vascular damage effect of circulating microparticles in patients with ACS is aggravated by type 2 diabetes.

As a common factor of both type 2 diabetes mellitus (T2DM) and acute coronary syndrome (ACS), circulating microparticles (MPs) may provide a link between these two diseases. The present study compared the content and function of MPs from patients with ACS with or without T2DM. MPs from healthy subjects (n=20), patients with ACS (n=24), patients with T2DM (n=20) and patients with combined ACS and T2DM (n=24) were obtained. After incubating rat thoracic tissue with MPs, the effect of MPs on endothelial­dependent vasodilatation, expression of caveolin­1 and endothelial nitric oxide synthase (eNOS), phosphorylation of eNOS at the S1177 and T495 sites and its association with heat shock protein 90 (Hsp90), and the generation of NO and superoxide anion (O2˙­) were determined. MP concentrations were higher in patients with T2DM and patients with ACS with or without T2DM than in healthy subjects. Moreover, MPs from patients with T2DM or ACS led to impairment in endothelial­dependent vasodilatation, decreased expression of NO, as well as eNOS and its phosphorylation at Ser1177 and association with Hsp90, but increased eNOS phosphorylation at T495, caveolin­1 expression and O2˙­ generation. These effects were strengthened by MPs from patients with ACS combined with T2DM. T2DM not only increased MP content but also resulted in greater vascular impairment effects in ACS. These results may provide novel insight into the treatment of patients with ACS and T2DM.

Complete chloroplast genome of Prunus fruticosa and its implications for the phylogenetic position within Prunus sensulato (Rosaceae).

Prunus fruticosa is a wild species of Prunus distributed across the central Eurasia. Here, we reported the complete chloroplast (cp) genome of P. fruticosa (GenBank accession number: MT916286). The cp genome was 158,217 bp long, with a large single-copy region (LSC) of 86,322 bp and a small single-copy region (SSC) of 19,153 bp separated by a pair of inverted repeats (IRs) of 26,371 bp. It encodes 129 genes, including 84 protein-coding genes, 37 tRNA genes, and 8 ribosomal RNA genes. We also reconstructed the phylogeny of Prunus sensu lato using maximum likelihood (ML) method, including our data and previously reported cp genomes of related taxa. The phylogenetic analysis indicated that P. fruticosa is closely related with Prunus avium.

The study on analysis of risk factors for severity of white matter lesions and its correlation with cerebral microbleeds in the elderly with lacunar infarction.

This study aimed to explore the risk factors for severity of white matter lesions and its correlation with in the elderly with lacunar infarction.Patients (range, 70-85 years) with lacunar infarction treated in a hospital in China from 2016 to 2017were enrolled. Fazekas rating scale (0-6 points) was used to assess severity of white matter lesions. Risk factors for the severity of white matter lesions and correlation between cerebral microbleeds and white matter lesions in the elderly with lacunar infarction were studied.The elderly (81-85 years' old, odds ratio [OR]: 2.423, 95% confidence interval [CI]: 1.795-3.271, P = .018; 76∼80 years' old, OR: 3.113, 95% CI: 1.723-5.625, P = .043), carotid atherosclerosis (OR: 3.062, 95% CI:1.715-5.468, P < .001), history of hypertension (OR: 3.694, 95% CI: 2.031-6.717, P < .001) were risk factors for the severity of white matter lesions. The white matter lesions score increased corresponding to increase in the cerebral microbleeds grade (P < .001). The white matter lesions score was higher in the cerebral microbleeds combined with the white matter lesions group than in the white matter lesions group (P < .01). After correcting the effects of age, there was a correlation between white matter lesions and cerebral microbleeds (P < .001). Logistic analysis revealed that the patients' age (81-85 years' old, OR: 2.722, 95% CI: 1.985-3.734, P = .019; 76∼80 years' old, OR: 1.857, 95% CI: 1.075-3.207, P = .031), history of hypertension (OR: 2.931, 95% CI: 1.136-7.567, P = 0.0.036), systolic blood pressure (OR: 1.049, 95% CI: 1.015-1.084, P = .007), high-sensitivity C-reactive protein (OR: 1.504, 95% CI: 1.254-1.803, P < .001), homocysteine (OR: 1.076, 95% CI: 1.020-1.136, P = .009), and carotid atherosclerosis (OR: 1.389, 95% CI: 1.103-1.748, P = .010) were significant risk factors for combined cerebral microbleeds with white matter lesions in patients with lacunar infarction.The elderly, carotid atherosclerosis, history of hypertension were risk factors for the severity of white matter lesions. Cerebral microbleeds were positively correlated with the severity of white matter lesions.

The genome of Chinese flowering cherry (Cerasus serrulata) provides new insights into Cerasus species.

Cerasus serrulata is a flowering cherry germplasm resource for ornamental purposes. In this work, we present a de novo chromosome-scale genome assembly of C. serrulata by the use of Nanopore and Hi-C sequencing technologies. The assembled C. serrulata genome is 265.40 Mb across 304 contigs and 67 scaffolds, with a contig N50 of 1.56 Mb and a scaffold N50 of 31.12 Mb. It contains 29,094 coding genes, 27,611 (94.90%) of which are annotated in at least one functional database. Synteny analysis indicated that C. serrulata and C. avium have 333 syntenic blocks composed of 14,072 genes. Blocks on chromosome 01 of C. serrulata are distributed on all chromosomes of C. avium, implying that chromosome 01 is the most ancient or active of the chromosomes. The comparative genomic analysis confirmed that C. serrulata has 740 expanded gene families, 1031 contracted gene families, and 228 rapidly evolving gene families. By the use of 656 single-copy orthologs, a phylogenetic tree composed of 10 species was constructed. The present C. serrulata species diverged from Prunus yedoensis ~17.34 million years ago (Mya), while the divergence of C. serrulata and C. avium was estimated to have occurred ∼21.44 Mya. In addition, a total of 148 MADS-box family gene members were identified in C. serrulata, accompanying the loss of the AGL32 subfamily and the expansion of the SVP subfamily. The MYB and WRKY gene families comprising 372 and 66 genes could be divided into seven and eight subfamilies in C. serrulata, respectively, based on clustering analysis. Nine hundred forty-one plant disease-resistance genes (R-genes) were detected by searching C. serrulata within the PRGdb. This research provides high-quality genomic information about C. serrulata as well as insights into the evolutionary history of Cerasus species.

Complete chloroplast genome of Cerasus kumanoensis (Rosaceae), a wild flowering cherry endemic to Kii Peninsula, Japan.

Cerasus kumanoensis is a recently described wild cherry species from the Kii Peninsula, Japan. Here we determined the first complete chloroplast genome of C. kumanoensis using genome skimming approach. The cp genome was 157,898 bp long, with a large single-copy region (LSC) of 85,926 bp and a small single-copy region (SSC) of 19,070 bp separated by a pair of inverted repeats (IRs) of 26,451 bp. It encodes 129 genes, including 84 protein-coding genes, 37 tRNA genes, and 8 ribosomal RNA genes. Besides, we reconstructed the phylogeny of Prunus using maximum likelihood (ML) method, including our data and previously reported cp genomes of related taxa. The phylogenetic analysis indicated that C. kumanoensis is close related with a group including Prunus takesimensis and P. speciosa.

Complete chloroplast genome of Prunus itosakura (Rosaceae), a wild flowering cherry from Japan.

Prunus itosakura is a flowering tree species with high ornamental and economic values. We determined the first complete chloroplast genome of P. itosakura using genome skimming approach. The cp genome was 157,813 bp long, with a large single-copy region (LSC) of 85,931 bp and a small single-copy region (SSC) of 19,120 bp separated by a pair of inverted repeats (IRs) of 26,381 bp. It encodes 129 genes, including 84 protein-coding genes, 37 tRNA genes, and 8 ribosomal RNA genes. We also reconstructed the phylogeny of Prunus sensu lato using maximum likelihood (ML) method, including our data and previously reported cp genomes of related taxa. The phylogenetic analysis indicated that P. itosakura is closely related with Prunus subhirtella var. subhirtella.

[Geographical characteristics of single nucleotide polymorphism of candidate genes associated with coronary artery disease in Chinese Han population].

OBJECTIVE: To investigate the geographical characteristics of single nucleotide polymorphism (SNP) of candidate genes associated with coronary artery disease in Chinese Han population. METHODS: Study population were Chinese Han nationality recruited from Xi'an, Shiyan and Ningbo districts. Patients with coronary artery disease were defined by coronary angiography with stenosis >or= 50% and control subjects with stenosis < 10%, respectively. The DNA was extracted from peripheral white blood cell by approach comprised proteinase K digestion, phenol and chloroform extraction as well as isopropanol precipitation. The SNP of ATP-binding cassette transporter (ABCA1)-G596A, cholesteryl ester transfer protein (CETP)-Taq1B, Lipoprotein lipase (LPL)-Hind III and LPL-Pvu II were genotyped by PCR-RFLPs, and verified by gene sequencing. RESULTS: A Total of 615 patients undertaken coronary angiography were recruited from cardiac center in Xi'an (220), Ningbo (209) and Shiyan district (186), China (mean age 60 +/- 10 years, 75.9% males). Diabetes mellitus was more prevalent in Xi'an Cohort population than Shiyan and Ningbo cohort (P < 0.01). Plasma total cholesterol, LDL cholesterol and triglyceride levels in Xi'an Cohort population were significantly higher, and HDL-C siginificantly lower than in Shiyan and Ningbo cohort population [HDL-C: (1.17 +/- 0.48) mmol/L vs. (1.25 +/- 0.33) mmol/L and (1.29 +/- 0.44) mmol/L, P < 0.05]. Distribution differences for ABCA1-G596A and CETP-Taq1B genotypes were found in Xi'an Cohort population compared to Ningbo and Shiyan cohorts (for ABCA1, Xi'an: 0.24, 0.53, 0.23 and Shiyan: 0.17, 0.62, 0.21 and Ningbo: 0.34, 0.37, 0.29, for GG, AG, AA, respectively, P < 0.01; and for CETP, Xi'an: 0.29, 0.54, 0.17 and Shiyan: 0.38, 0.40, 0.22 and Ningbo: 0.39, 0.49, 0.12 for B1B1, B1B2, B2B2, respectively, P < 0.01), but not for LPL variants. ABCA1-G596A variant predicted HDL-C [Xi'an: (1.2 +/- 0.3) mmol/L, (1.3 +/- 0.2) mmol/L and (1.4 +/- 0.4) mmol/L, P = 0.01; Shiyan: (1.1 +/- 0.4) mmol/L: (1.2 +/- 0.3) mmol/L and (1.3 +/- 0.4) mmol/L, P = 0.03; Ningbo, (1.2 +/- 0.3) mmol/L, (1.3 +/- 0.4) mmol/L and (1.4 +/- 0.3) mmol/L, across GG, GA to AA genotype, respectively, P = 0.01] and TG levels [Xi'an: (2.4 +/- 1.3) mmol/L, (1.9 +/- 0.9) mmol/L and (1.6 +/- 0.8) mmol/L, P < 0.01; Shiyan: (2.1 +/- 1.0) mmol/L, (1.9 +/- 0.8) mmol/L and (1.8 +/- 0.7) mmol/L, P = 0.03; Ningbo: (1.9 +/- 1.1) mmol/L, (1.8 +/- 0.9) mmol/L and (1.6 +/- 0.7) mmol/L, across GG, GA to AA genotype, P = 0.05] with dose-dependent relationship. LPL-Hind III (+) carriers had higher triglycerides in three cohort population [Xi'an: (2.2 +/- 1.0) mmol/L, (1.8 +/- 0.9) mmol/L, (1.6 +/- 0.7) mmol/L, P = 0.01; Shiyan: (2.1 +/- 0.7) mmol/L, (1.9 +/- 1.0) mmol/L, (1.7 +/- 0.6) mmol/L, P = 0.01; Ningbo: (1.8 +/- 1.0) mmol/L, (1.6 +/- 0.6) mmol/L and (1.4 +/- 0.5) mmol/L, for +/+, +/- and -/- genotypes, respectively, P = 0.001]. SNP of CETP-Taq1B, LPL-Hind III and LPL-Pvu II predicted HDL-C and/or TG levels in different cohort population with different manners. All these SNP were not significantly associated with the development of coronary artery disease (all P > 0.05). CONCLUSION: A geographical heterogeneity of environmental and genetic risk factors related to the development of coronary artery disease exists in Chinese Han population. Irrespective of the different geographical cohort of Chinese Han population, the SNP of candidate genes can partly predict the differences in risk-related plasma HDL-C and/or TG levels rather than angiographic coronary artery disease.

Endothelial damage effects of circulating microparticles from patients with stable angina are reduced by aspirin through ERK/p38 MAPKs pathways.

INTRODUCTION: Platelet activation participates in the development of both coronary artery disease (CAD) and circulating microparticles (MPs). As a commonly used medicine for coronary heart disease, whether aspirin affects the function of MPs remains unclear. AIMS: This study was designed to test MPs from healthy subjects, and stable angina (SA) patients before and after aspirin administration were obtained. MPs origins were tested by flow cytometry. Rat thoracic aortas were incubated with MPs (with or without aspirin) to determine the effects of MPs on expression of ERK1/2, JNKs, and p38 MAPK. Affect on levels of NF-κB, VCAM-1, NO, and O2-. RESULTS: Compared with healthy subjects, MPs concentrations increased in SA patients, but decreased after aspirin administration. According to flow cytometry, aspirin mainly decreased platelet-derived MP. MPs from SA patients decreased the expression of ERK1/2, increased expression of p38 MAPKs, JNKs. Increased NF-κB, VCAM-1, and (O2-) levels decreased NO content. Aspirin therapy significantly inhibited function of MPs from SA patients, and pathway inhibitors (ERK1/2 inhibitor PD98059, p38 MAPKs inhibitor SB203580, NF-kB inhibitor PDTC) show similar effects with aspirin. CONCLUSION: These results indicate that the pro-inflammatory, oxidative stress, procoagulant, and adhesion properties of MPs can be partly blocked by aspirin via the ERK-NO/O2- and p38 -NF-κB-VCAM-1 signal pathway, which clarified other functions beyond anti-atherothrombotic of aspirin.

Prevention of pericardial constriction by transcatheter intrapericardial fibrinolysis with urokinase.

OBJECTIVE: To investigate whether intrapericardial urokinase irrigation along with pericardiocentesis could prevent pericardial constriction in patients with infectious exudative pericarditis. METHODS: A total of 94 patients diagnosed as infectious exudative pericarditis (34 patients with purulent pericarditis and 60 with tuberculous pericarditis, the disease courses of all patients were less than 1 month), 44 males and 50 females, aged from 9 to 66 years (mean 45.4 +/- 14.7 years), were consecutively recruited from 1993 to 2002. All individuals were randomly given either intrapericardial urokinase along with conventional treatment in study group, or conventional treatment alone (including pericardiocentesis and drainage) in control group. The dosage of urokinase ranged from 200000 to 600000 U (mean 320000 +/- 70000 U). The immediate effects were detected by pericardiography with sterilized air and diatrizoate meglumine as contrast media. The long-term investigation depended on the telephonic survey and echocardiographic examination. The duration of following-up ranged from 8 to 120 months (mean 56.8 +/- 29.0 months). RESULTS: Percutaneous intrapericardial urokinase irrigation promoted complete drainage of pericardial effusion, significantly reduced the thickness of pericardium (from 3.1 +/- 1.6 mm to 1.6 +/- 1.0 mm in study group, P < 0.001; from 3.4 +/- 1.6 mm to 3.2 +/- 1.8 mm in control group, P > 0.05, respectively), and alleviated the adhesion. Intrapericardial bleeding related to fibrinolysis was found in 6 of 47 patients with non-blood pericardial effusion and no systemic bleeding and severe puncture-related complication was observed. In follow-up, there was no cardiac death, and pericardial constriction events were observed in 9 (19.1%) of study group and 27 (57.4%) of control group. Cox analysis illustrated that urokinase could significantly reduce the occurrence of pericardial constriction (relative hazard coefficient = 0.185, P < 0.0001). CONCLUSION: The early employment of intrapericardial fibrinolysis with urokinase and pericardiocentesis appears to be safe and effective in preventing the development of pericardial constriction in patients with infectious exudative pericarditis.

Effects of brain IKKß gene silencing by small interfering RNA on P-glycoprotein expression and brain damage in the rat kainic acid-induced seizure model.

Multidrug resistance mediated by over-expression of P-glycoprotein (P-gp) in brain is an important mechanism accounting for the drug-therapy failure in epilepsy. Over-expression of P-gp in epilepsy rat brain may be regulated by inflammation and nuclear factor-kappa B (NF-κB) activation. Inhibitory κ B kinase subunit ß (IKKß) is an up-stream molecular controlling NF-κB activation. With the small interfering RNA (siRNA) technique and kainic acid (KA)-induced rat epileptic seizure model, the present study was aimed to further evaluate the role of NF-κB inhibition, via blocking IKKß gene transcription, in the epileptic brain P-gp over-expression, seizure susceptibility, and post-seizure brain damage. siRNA targeting IKKß was administered to rats via intracerebroventricular injection before seizure induction by KA microinjection; scrambled siRNA was used as control. Brain mRNA and protein levels of IKKß and P-gp were detected by RT-PCR and immunohistochemistry. NF-κB activity was measured by electrophoretic mobility shift assay. Latency to grade III or V seizure onset was recorded, brain damage was evaluated by neuronal cell counting and epileptiform activity was monitored by electroencephalography. IKKß siRNA pre-treatment inhibited NF-κB activation and abolished P-gp over-expression in KA-induced epileptic rat brain, accompanied by decreased seizure susceptibility. These findings suggested that epileptogenic-induced P-gp over-expression could be regulated by IKKß through the NF-κB pathway.

A meta-analysis of pro-inflammatory cytokines in the plasma of epileptic patients with recent seizure.

This review was to assess the concentration changing trends of various cytokines in plasma of epilepsy patients after recent seizure, as well as to assess the differences between temporal lobe epilepsy (TLE) and extra-TLE (XLE) patients. We performed a meta-analysis of studies measuring cytokine concentration in plasma of patients suffering from epilepsy after recent seizure, by searches of the English literature in Pubmed and Embase databases (to July 1st 2010) and a manual search of references. A random-effects model was used to do accumulative analysis for the included studies by RevMan 5.0 software. Eight studies were included and analyzed. We found the plasma concentrations of interleukin-6 (IL-6) within 72h after seizure were significantly increased in epileptic patients compared with control subjects (211 epilepsy patients vs. 564 controls, overall weighted mean difference 1.27pg/ml, 95% confidence interval 0.72-1.82, P<0.0001). There were no significant differences for IL-1 beta and, IL-1 receptor antagonist (IL-1RA) between the two groups. The concentration changes of IL-6 and IL-1RA were not significantly different between TLE patients and XLE patients. The result of this meta-analysis revealed significantly higher concentrations of the pro-inflammatory cytokines IL-6 in epileptic seizure patients compared with control subjects. Further rigorous studies are needed to clarify the precise role of cytokines in epilepsy.