Analyzing Complex Problem Solving by Dynamic Brain Networks

Complex problem solving is a high level cognitive task of the human brain, which has been studied over the last decade. Tower of London (TOL) is a game that has been widely used to study complex problem solving. In this paper, we aim to explore the underlying cognitive network structure among anatomical regions of complex problem solving and its subtasks, namely planning and execution. A new computational model for estimating a brain network at each time instant of fMRI recordings is proposed. The suggested method models the brain network as an Artificial Neural Network, where the weights correspond to the relationships among the brain anatomic regions. The first step of the model is preprocessing that manages to decrease the spatial redundancy while increasing the temporal resolution of the fMRI recordings. Then, dynamic brain networks are estimated using the preprocessed fMRI signal to train the Artificial Neural Network. The properties of the estimated brain networks are studied in order to identify regions of interest, such as hubs and subgroups of densely connected brain regions. The representation power of the suggested brain network is shown by decoding the planning and execution subtasks of complex problem solving. Our findings are consistent with the previous results of experimental psychology. Furthermore, it is observed that there are more hubs during the planning phase compared to the execution phase, and the clusters are more strongly connected during planning compared to execution

Flavopiridol Induces Apoptosis via Mitochondrial Pathway in B16F10 Murine Melanoma Cells and a Subcutaneous Melanoma Tumor Model

Flavopiridol is a cyclin-dependent kinase (CDK) inhibitor that promotes cell cycle arrest. We aimed to examine the anti-proliferative effects of the flavopiridol and oxaliplatin combination on p16INK4A deficient melanoma cells B16F10 and also its apoptotic effects on a subcutaneously injected B16F10 allograft melanoma tumor model. Flavopiridol and oxaliplatin treated B16F10 cell viability was determined by MTT assay. C57BL6 mice were injected with B16F10 cells and treated with flavopiridol after tumor implantation. BRAF and BCL2L1 mRNA expression levels were measured using reverse transcription-polymerase chain reaction (RT-PCR). Caspase 9 and caspase 3/7 activity were determined by activity assay kits. Proliferating cell nuclear antigen (PCNA) and B-cell lymphoma 2 (BCL-2) protein expression levels were analyzed immunohistochemically. Flavopiridol and oxaliplatin decreased cell death. Flavopiridol enhanced caspase 3/7 and caspase 9 activities in vitro and in vivo in a dose dependent manner via the mitochondrial apoptotic pathway. Even though there was a significant increase in Bcl-2 staining, PCNA staining was decreased in flavopiridol-administered mice. Decreased PCNA expression showed antiproliferative effects of flavopiridol which might be the result of cell-cycle arrest. Flavopiridol can be used as a cell cycle inhibitor, which induced apoptosis through the mitochondrial pathway, independently from BCL2 in B16F10 cells and B16F10 injected C57BL6 allografts. </p

Inhibition of ErbB2 by Herceptin reduces viability and survival, induces apoptosis and oxidative stress in Calu-3 cell line

Human epidermal growth factor receptor 2 (ErbB2) amplification and overexpression has been seen in many cancer types including non-small cell lung cancer (NSCLC). Thus, ErbB2 is an important target for cancer therapies. Increased ErbB2 expression has been associated with drug resistance in cancer cells. Herceptin is a humanized monoclonal antibody that targets the extracellular domain of ErbB2. In this study, we aimed to block ErbB2 signaling with Herceptin and assess cytotoxicity and effects on apoptosis, oxidative stress, nuclear factor kappa-B (NF-kB), and Survivin expression in Calu-3 cell line. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay were used to assess cell viability as a marker of proliferation. Acridine orange/ethidium bromide (AO/EB) staining and caspase 3/7 activity were measured as the markers of apoptosis. The relative expressions of NF-kB-p50 and Survivin mRNAs were evaluated. Activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), and the levels of glutathione (GSH) and reactive oxygen species (ROS) were determined in a time- and dose-dependent manner. Our results show that Herceptin treatment inhibits cell proliferation and activates apoptosis but without effects on Survivin and NF-kB expression in Calu-3 cell line. Intracellular glutathione levels and SOD and CAT activities were decreased in a time- and dose-dependent manner associated with oxidative stress. Also, ROS were increased at 24 h. These results provide evidence that Herceptin can be used as a cytotoxic and apoptotic agent in NSCLC

Evaluation of Advanced Oxidation Protein Products, Prooxidant-Antioxidant Balance, and Total Antioxidant Capacity in Untreated Vitiligo Patients

Vitiligo is a chronic, common disease of unknown etiology, and oxidative stress is suggested to have a role in its etiopathogenesis. Objective: Advanced oxidation protein products (AOPPs), prooxidant-antioxidant balance (PAB), and ferric-reducing antioxidant power (FRAP) were evaluated regarding their role in the pathogenesis of vitiligo as well as their relationship with clinical presentation and disease severity, and these parameters were compared with those of healthy controls. Methods: The study included 53 patients with vitiligo and 20 healthy volunteers as the control group. AOPP level, PAB, and FRAP were determined by colorimetric methods. Results: PAB and FRAP level were significantly higher in patients with vitiligo than in healthy controls (p < 0.001). The AOPP levels in vitiligo patients were not statistically significantly higher than those in healthy controls. The Vitiligo Area Scoring Index positively correlated with disease duration (r(s): 0.531, p <0.001). Conclusion: To the best of our knowledge, this is the first report of AOPP and PAB status in vitiligo. PAB may be used as an indicator for Oxidative stress in the etiopathogenesis of vitiligo. Our results show that these parameters may play a major role in the melanocyte damage observed in vitiligo. Further studies are required to confirm the mechanisms underlying this effect.WOS:0003526594000092-s2.0-84925684375PubMed: 2583435

Relationship between LPA SNPs and inflammatory burden in patients with preeclampsia to address future cardiovascular risk

Objective: The study tested whether cardiovascular corresponding LPA risk genotypes improve pre-eclampsia and coronary heart disease (CHD) risk prediction beyond conventional risk factors. Background: Studies have shown that women specific risk factors for cardiovascular disease (CVD) have taken an attention recently. It might be possible to identify women who have the highest risk in developing CVD in their further lives. It is well-known that Lp(a) levels have an impact on increased risk of CVD which is affected by LPA gene. Further, LPA risk genotypes are not considered in cardiovascular risk prediction. Methods: We have included 200 pregnant Turkish women into the study. We stratified the preeclamptic (PE) group: early (EOP) (28.7 +/- 3.0 weeks) and late onset (LOP) (36.0 +/- 1.4 weeks). 14 LPA SNPs were evaluated in the study. Rs9355296 and rs3798220 were found as independent risk factors for preeclampsia by logistic regression analysis. A positive correlation was found between rs9355296 and the diagnostic criteria of preeclampsia. Further rs9355296 G/* carriers have higher vascular inflammation rather than AA carriers. Conclusions: The findings reveal that LPA genetic variability with high inflammatory response might be an indication of future cardiovascular events

Serum endocan concentration in women with pre-eclampsia

Purpose To investigate serum endocan levels in pregnant subjects with and without pre-eclampsia

Flavopiridol's antiproliferative effects in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is largely refractory to surgical operation, radiotherapy, and chemotherapy in use today. Remaining lifetime accounting for the GBM-affected patients varies between 12 and 16 months generally. The most frequently altered genes in GBM are p53, epidermal growth factor receptor, PTEN, and cyclin-dependent kinase inhibitor 2A. Our aim is to investigate the antiproliferative and apoptotic effects of flavopiridol, a cyclin-dependent kinases and specific phosphokinase inhibitor, on glioblastoma cell lines having different genetic profiles: U87MG, U118MG, and T98G