Effects of a Single-Session Cognitive Enhancement Fitness Program on Serum Brain-Derived Neurotrophic Factor Levels and Cognitive Function in Middle-Aged Women.

Few studies have been undertaken to develop cognitive functional improvement-focused exercise programs and determine their effect. The objectives of this study were to evaluate the effects of a cognitive enhancement fitness program (CEFP) on short-term memory and serum brain-derived neurotrophic factor (BDNF) levels according to the cognitive state in middle-aged women. A total of 30 healthy volunteers aged 40-59 years were divided into two groups, that is, a mild cognitive impairment (MCI) group and a non-MCI group based on results from the Korean Dementia Screening Questionnaire. A single-session CEFP was conducted over 50 min and consisted of four parts: warm-up, low intensity interval circulation dance exercises, moderate intensity resistance exercises using elastic bands, and cool-down. Serum BDNF levels were measured by ELISA and short-term memory determined by forward digit/word span test was assessed before and after CEFP. After CEFP, forward digit/word span test scores and BDNF levels increased to median 119.2%/115.1% and 118.7%, respectively. After CEFP, the MCI and non-MCI groups produced higher forward digit span test scores (from 6.7 ± 1.5 to 7.5 ± 1.4 points, p = 0.023 and from 6.2 ± 2.0 to 7.0 ± 2.1 points, P=0.011, respectively). After CEFP, forward word span scores and BDNF levels increased (from 3.5 ± 1.7 to 4.6 ± 1.8 points, p = 0.029 and from 610.8 ± 221.1 to 757.9 ± 267.9 pg/ml, p = 0.017, respectively) in non-MCI group only. No group differences were observed between change in short-term memory and change in BDNF. Short-term memory and BDNF levels after CEFP were found to be negatively correlated with age, but pre- to post-intervention changes in short-term memory and BDNF were not. The present study shows that a single, 50-minute CEFP improved short-term memory and increased serum BDNF levels in healthy middle-aged women, especially those without MCI.

Clinical symptoms associated with suicidality in patients with panic disorder.

BACKGROUND: Patients with panic disorder have higher rates of suicide than the general population. Among panic disorder subjects, early onset, female gender, alcohol abuse, and mood disorder increase the risk of suicidality. However, less is known about the unique relationships between discrete DSM-IV panic symptoms and higher suicidality. Therefore, in the current study we examined the panic symptom profile that is associated with higher suicidality in a sample of outpatients with panic disorder. METHODS: This cross-sectional study included 427 patients diagnosed with current panic disorder on the basis of the DSM-IV-TR. In order to assess the contribution of the clinical variables, a univariate logistic regression was carried out examining the relationships between the demographic variables, suicidality from the suicide module of the Korean version of the MINI International Neuropsychiatric Interview Plus, and DSM-IV panic symptoms. Additionally, a multivariate logistic regression was performed to identify specific panic symptoms that were significant risk factors for suicidality among patients with current panic disorder. RESULTS: We found that 74 (17.33%) panic disorder patients experienced high suicidality. Univariate analyses showed that high suicidality was significantly associated with a younger age (OR = 13.66; 95% CI 2.68-69.70), comorbid depressive disorders (OR = 4.57; 95% CI 2.57-8.11), and the following panic symptoms: palpitations (OR = 2.20; 95% CI 0.90-5.35), trembling (OR = 0.61; 95% CI 0.362-1.18), nausea or abdominal distress (OR = 1.77; 95% CI 0.96-3.27), fear of losing control or going crazy (OR = 2.18; 95% CI 1.12-4.23), and paresthesia (OR = 1.57; 95% CI 0.83-2.98). Multivariate logistic regression analyses demonstrated that specific panic symptoms, such as palpitations (adjusted OR = 2.69; 95% CI 1.08-6.73) and fear of losing control or going crazy (adjusted OR = 2.28; 95% CI 1.21-4.31), were related to suicidality after controlling for confounding factors. CONCLUSION: Some panic symptoms (e.g. palpitations and fear of losing control or going crazy) are associated with a risk of suicidality among patients with panic disorder. A priori identification of high-risk suicidal subjects could lead to effective treatment strategies for panic disorder.

Antiapoptotic effects of Phe140Asn, a novel human granulocyte colony-stimulating factor mutant in H9c2 rat cardiomyocytes.

Granulocyte colony-stimulating factor (G-CSF) is used for heart failure therapy and promotes myocardial regeneration by inducing mobilization of bone marrow stem cells to the injured heart after myocardial infarction; however, this treatment has one weakness in that its biological effect is transient. In our previous report, we generated 5 mutants harboring N-linked glycosylation to improve its antiapoptotic activities. Among them, one mutant (Phe140Asn) had higher cell viability than wild-type hG-CSF in rat cardiomyocytes, even after treatment with an apoptotic agent (H2O2). Cells treated with this mutant significantly upregulated the antiapoptotic proteins, and experienced reductions in caspase 3 activity and PARP cleavage. Moreover, the total number of apoptotic cells was dramatically lower in cultures treated with mutant hG-CSF. Taken together, these results suggest that the addition of an N-linked glycosylation was successful in improving the antiapoptotic activity of hG-CSF, and that this mutated product will be a feasible therapy for patients who have experienced heart failure.

Enhanced biological effects of Phe140Asn, a novel human granulocyte colony-stimulating factor mutant, on HL60 cells.

Granulocyte colony-stimulating factor (G-CSF) is a cytokine secreted by stromal cells and plays a role in the differentiation of bone marrow stem cells and proliferation of neutrophils. Therefore, G-CSF is widely used to reduce the risk of serious infection in immunocompromised patients; however, its use in such patients is limited because of its non-persistent biological activity. We created an N-linked glycosylated form of this cytokine, hG-CSF (Phe140Asn), to assess its biological activity in the promyelocyte cell line HL60. Enhanced biological effects were identified by analyzing the JAK2/STAT3/survivin pathway in HL60 cells. In addition, mutant hG-CSF (Phe140Asn) was observed to have enhanced chemoattractant effects and improved differentiation efficiency in HL60 cells. These results suggest that the addition of N-linked glycosylation was successful in improving the biological activity of hG-CSF. Furthermore, the mutated product appears to be a feasible therapy for patients with neutropenia.

Molecular characterization of rotavirus diarrhea among children in South Korea: detection of an unusual G11 strain.

Among 312 rotavirus-positive samples collected from eight hospitals across South Korea during 2008 and 2009, the most prevalent circulating G genotype was G1 (35.9%), followed by G3 (24.7%), G2 (17.0%), G4 (7.7%), and G9 (2.6%). Notably, one unusual G11 lineage III strain-the first hypoendemic infection case in the world-was found. Of the P genotypes, P[8] (43.9%) was the most common, followed by P[6] (29.5%), P[4] (9.3%) and P[9] (0.6%). Determining G- and P-type combinations showed that G1P[8] was the most prevalent (20.5%), followed by G2P[6] (12.8%) and G3P[8] (12.8%). These findings provide new information concerning the current prevalence and spread of the rare G11 rotavirus.

Improvement of recombinant hGM-CSF production by suppression of cysteine proteinase gene expression using RNA interference in a transgenic rice culture.

Recombinant proteins have been previously synthesized in a transgenic rice cell suspension culture system with the rice amylase 3D promoter, which can be induced via sugar starvation. However, the secreted recombinant proteins have been shown to be rapidly decreased as the result of proteolytic degradation occurring during prolonged incubation. The secreted proteases were identified via two-dimensional electrophoresis (2-DE) and ESI/Q-TOF mass spectrometry analyses. The internal amino acid sequences of 8 of 37 spots corresponded to cysteine proteinase (CysP), which is encoded for by Rep1 and EP3A. This result shows that CysP is a major secreted protease in rice cell suspension cultures following induction via sugar starvation. Intron-containing self-complementary hairpin RNA (ihpRNA)-mediated post-transcriptional gene silencing (PTGS) was applied to suppress the expression of CysP in rice cell suspension cultures. The reduction of rice CysP mRNA and the detection of siRNA specific to CysP, an initiator of RNAi, were verified via Northern blot analysis and RNase protection assays, respectively, thereby indicating that PTGS operated successfully in this system. The analysis of total secreted protease and CysP activities evidenced lower activity than was observed with the wild-type. Furthermore, suspension cultures of rice cells transformed with both hGM-CSF and the gene expressing the ihpRNA of CysP evidenced a reduction in total protease and CysP activities, and an up to 1.9-fold improvement in hGM-CSF production as compared to that observed in a rice cell line expressing hGM-CSF only. These results demonstrate the feasibility of the suppression of CysP via RNA interference to reduce protease activity and to increase target protein accumulation in rice cell suspension cultures.

Asymmetric synthesis of (+)-cis-nemorensic acid from a chiral Diels-Alder adduct of 2,5-dimethylfuran.

(+)-cis-Nemorensic acid was synthesized from a chiral Diels-Alder adduct prepared by a catalytic enantioselective Diels-Alder reaction with 2,5-dimethylfuran and 2,2,2-trifluoroethyl acrylate.

Monoclonal antibody to CD9 inhibits platelet-induced human endothelial cell proliferation.

Platelets are anucleate cytoplasmic fragments derived from bone marrow megakaryocytes, and endothelial cells constitute the barrier between bloodstream and adjacent tissues. Although platelets are thought to regulate the biological functions of endothelial cells, the molecular mechanisms involved are poorly understood. With human umbilical vein endothelial cells and freshly isolated platelets, we established an in vitro model of platelet-induced endothelial cell proliferation. Platelets stimulated endothelial cell proliferation in a dose-dependent manner and transwell experiments with semi-permeable membranes suggested that direct cell-to-cell contacts were required. We developed mAbs against platelets and selected a mAb that blocks their proliferative effect. We purified the antigen by immunoprecipitation and identified it by Q-TOF MS analysis as the tetraspanin CD9. Since both platelets and endothelial cells expressed CD9 strongly on their surfaces we carried out a pre-treatment experiment that showed that CD9 molecules on the endothelial cells participate in the mitogenic effect of the platelets. The inhibitory effect of our mAb was comparable to that of a well-known functional anti-CD9 mAb. These results suggest that the tetraspanin CD9 plays an important role in endothelial regeneration.

Human follicular dendritic cells express prostacyclin synthase: a novel mechanism to control T cell numbers in the germinal center.

Stromal cells in the lymphoid organs provide a microenvironment where lymphocytes undergo various biological processes such as development, homing, clonal expansion, and differentiation. Follicular dendritic cells (FDCs) in the primary and secondary follicles of the peripheral lymphoid tissues interact with lymphocytes by contacting directly or producing diffusible molecules. To understand the biological role of human FDC at the molecular level, we developed a mAb, 3C8, that recognizes FDC but not bone marrow-derived cells. Through expression cloning and proteome analysis, we identified the protein that is recognized by 3C8 mAb, which revealed that FDC expresses prostacyclin synthase. The 3C8 protein purified from FDC-like cells indeed displayed the enzymatic activity of prostacyclin synthase and converted PGH2 into prostacyclin. In addition, prostacyclin significantly inhibited proliferation of T cells but delayed their spontaneous apoptosis. These findings may help explain why T cells constitute only a minor population compared with B cells in the germinal center.

Detection of antibodies against glucose 6-phosphate isomerase in synovial fluid of rheumatoid arthritis using surface plasmon resonance (BIAcore).

We have used a surface plasmon resonance biosensor (SPR, BIACORE 2000) to detect antibodies against glucose 6-phosphate isomerase (GPI) in synovial fluids of rheumatoid arthritis (RA) and osteoarthritis (OA). Recombinant human GPI proteins fused with or without NusA were expressed in E. coli, purified to homogeneity and immobilized in flow cells of CM5 sensor chips. The flow cells immobilized with NusA protein or bovine serum albumin were used to monitor non-specific binding. Synovial fluid samples from RA patients showed a significantly higher level of binding to recombinant GPI proteins than samples from OA patients. Proteins which bound to the recombinant GPI proteins were confirmed to be immunoglobulin through the administration of anti-human immunoglobulin. NusA fusion protein was excellent for this assay because of a low background binding activity in the SPR analysis and its advantage of increased solubility in recombinant protein production. These results suggested a useful utilization of recombinant NusA-GPI fusion protein for the detection of autoantibodies against GPI in RA patients.

Interleukin-4 inhibits the vascular endothelial growth factor- and basic fibroblast growth factor-induced angiogenesis in vitro.

The role of interleukin-4 (IL-4) in the inflammatory process has emerged recently. In this study, we investigated the effect of IL-4 on the angiogenic process in an in vitro experimental system. IL-4 significantly inhibited the proliferation of human umbilical vein endothelial cells (HUVEC) that was induced by the vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). VEGF- or bFGF-induced HUVEC chemotaxis was abrogated by the IL-4 treatment. In addition, the formation of tube-like structures by HUVEC in the presence of VEGF or bFGF was also severely down-regulated by IL-4. The inhibitory effects on the critical steps of angiogenesis were not observed with IL-6 that is abundantly found in the inflamed tissue. Our results suggest that IL-4 may play a regulatory role in normal physiology and provide the potential possibility for IL-4 as a therapeutic agent in the intervention of angiogenesis-related diseases.