Go/No-Go Ratios Modulate Inhibition-Related Brain Activity: An Event-Related Potential Study

(1) Background: Response inhibition refers to the conscious ability to suppress behavioral responses, which is crucial for effective cognitive control. Currently, research on response inhibition remains controversial, and the neurobiological mechanisms associated with response inhibition are still being explored. The Go/No-Go task is a widely used paradigm that can be used to effectively assess response inhibition capability. While many studies have utilized equal numbers of Go and No-Go trials, how different ratios affect response inhibition remains unknown; (2) Methods: This study investigated the impact of different ratios of Go and No-Go conditions on response inhibition using the Go/No-Go task combined with event-related potential (ERP) techniques; (3) Results: The results showed that as the proportion of Go trials decreased, behavioral performance in Go trials significantly improved in terms of response time, while error rates in No-Go trials gradually decreased. Additionally, the NoGo-P3 component at the central average electrodes (Cz, C1, C2, FCz, FC1, FC2, PCz, PC1, and PC2) exhibited reduced amplitude and latency; (4) Conclusions: These findings indicate that different ratios in Go/No-Go tasks influence response inhibition, with the brain adjusting processing capabilities and rates for response inhibition. This effect may be related to the brain's predictive mechanism model

The p38 MAPK-regulated PKD1/CREB/Bcl-2 pathway contributes to selenite-induced colorectal cancer cell apoptosis in vitro and in vivo

AbstractSupranutritional selenite has anti-cancer therapeutic effects in vivo; however, the detailed mechanisms underlying these effects are not clearly understood. Further studies would broaden our understanding of the anti-cancer effects of this compound and provide a theoretical basis for its clinical application. In this study, we primarily found that selenite exposure inhibited phosphorylation of cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), leading to suppression of Bcl-2 in HCT116 and SW480 colorectal cancer (CRC) cells. Moreover, the selenite-induced inhibitory effect on PKD1 activation was involved in suppression of the CREB signalling pathway. Additionally, we discovered that selenite treatment can upregulate p38 MAPK phosphorylation, which results in inhibition of the PKD1/CREB/Bcl-2 survival pathway and triggers apoptosis. Finally, we established a colorectal cancer xenograft model and found that selenite treatment markedly inhibits tumour growth through the MAPK/PKD1/CREB/Bcl-2 pathway in vivo. Our results demonstrated that a supranutritional dose of selenite induced CRC cell apoptosis through inhibition of the PKD1/CREB/Bcl-2 axis both in vitro and in vivo

ATF4 activation by the p38MAPK–eIF4E axis mediates apoptosis and autophagy induced by selenite in Jurkat cells

AbstractPrevious studies have shown that selenite exerts pro-apoptosis and pro-autophagy effects and is associated with the activation of ER stress in T-cell acute lymphoblastic leukemia (T-ALL). Herein we demonstrate the underlying mechanisms by which the activation of p38MAPK plays essential roles in apoptosis and autophagy and the coordination of cellular metabolic processes during leukemia therapy. MKK3/6-dependent activation of p38MAPK is required for the phosphorylation of eIF4E, thus initiating the translation of ER stress-related transcription factor ATF4. Upregulated ATF4 results in the transcriptional initiation of the apoptosis-related chop gene and autophagy-related map1lc3b gene, through which selenite links ER stress to apoptosis and autophagy during leukemia treatment. Moreover, autophagy induction enhances cell apoptosis under this condition

Microphase Separation Induced by Differential Interactions in Diblock Copolymer/Homopolymer Blends

Phase behavior of diblock copolymer/homopolymer blends (AB/C) is investigated theoretically. The study focuses on a special case where all three binary pairs, A/B, B/C and C/A, are miscible. Despite the miscibility of the binary pairs, a closed-loop immiscible region exists in the AB/C blends when the A/C and B/C pair interactions are sufficiently different. Inside the closed-loop, the system undergoes microphase separation, exhibiting different ordered structures. This phenomenon is enhanced when the homopolymer (C) interacts more strongly to one of the blocks (A or B).Comment: 19 pages, 7 figures, submitted to J. Chem. Phy

Sodium selenite alters microtubule assembly and induces apoptosis in vitro and in vivo

BACKGROUND: Previous studies demonstrated that selenite induced cancer-cell apoptosis through multiple mechanisms; however, effects of selenite on microtubules in leukemic cells have not been demonstrated. METHODS: The toxic effect of selenite on leukemic HL60 cells was performed with cell counting kit 8. Selenite effects on cell cycle distribution and apoptosis induction were determined by flow cytometry. The contents of cyclin B1, Mcl-1, AIF, cytochrome C, insoluble and soluble tubulins were detected with western blotting. Microtubules were visualized with indirect immunofluorescence microscopy. The interaction between CDK1 and Mcl-1 was assessed with immunoprecipitation. Decreasing Mcl-1 and cyclin B1 expression were carried out through siRNA interference. The alterations of Mcl-1 and cyclin B1 in animal model were detected with either immunohistochemical staining or western blotting. In situ detection of apoptotic ratio was performed with TUNEL assay. RESULTS: Our current results showed that selenite inhibited the growth of HL60 cells and induced mitochondrial-related apoptosis. Furthermore, we found that microtubule assembly in HL60 cells was altered, those cells were arrested at G2/M phase, and Cyclin B1 was up-regulated and interacted with CDK1, which led to down-regulation of the anti-apoptotic protein Mcl-1. Finally, in vivo experiments confirmed the in vitro microtubule disruption effect and alterations in Cyclin B1 and Mcl-1 levels by selenite. CONCLUSIONS: Taken together, the results from our study indicate that microtubules are novel targets of selenite in leukemic HL60 cells

Elevated plasma levels of pigment epithelium-derived factor correlated with inflammation and lung function in COPD patients

Rationale: Pigment epithelium-derived factor (PEDF) is a 50 kD small secreting glycoprotein that participates in multiple physiological and pathological processes. Recent studies have reported that PEDF plays an important role in inflammatory responses in several diseases. However, the role of PEDF in the pathogenesis of chronic obstructive pulmonary disease (COPD) remains unclear. Objective: The aim of the present study is to explore the potential relationship between PEDF and COPD. Methods: We used differential proteomics – stable isotope labeling with amino acids in cell culture – to investigate protein expression profile changes in cigarette smoke extract-treated pulmonary cells and found that the neurotrophic and antiangiogenic protein PEDF was abnormally expressed. Furthermore, Western blotting was used to detect the expression of PEDF in the lung tissue of rats that were exposed to cigarette smoke. Eighty subjects between the ages of 40–90 years, including 20 healthy nonsmokers, ten smoking volunteers, and 50 COPD patients, were recruited from September 2012 until August 2013 in Sichuan Province, People’s Republic of China. We measured the plasma PEDF concentration and classic proinflammatory cytokines by multiplex enzyme-linked immunosorbent assay. In addition, we performed a spirometry examination to diagnose COPD patients and we also analyzed the correlation between PEDF and lung function. Results: First, we found that the expression of PEDF in cigarette smoke extract-treated cells increased 16.2-fold when compared with the control group. Next, we confirmed that 4 weeks’ exposure to cigarette smoke can upregulate PEDF levels in rat lung tissues. We also discovered that plasma PEDF in COPD patients was significantly increased when compared with either healthy nonsmoking or smoking subjects. Furthermore, circulating PEDF was correlated with inflammatory cytokine and blood neutrophil numbers, but it was reversely associated with a decline in forced expiratory volume in 1 second percent predicted. Conclusion: Our findings provide a novel link between PEDF and COPD. Elevated PEDF levels may be involved in promoting the development of COPD by performing proinflamma-tory functions

Metformin Ameliorates Hepatic Steatosis and Inflammation without Altering Adipose Phenotype in Diet-Induced Obesity

Non-alcoholic fatty liver disease (NAFLD) is closely associated with obesity and insulin resistance. To better understand the pathophysiology of obesity-associated NAFLD, the present study examined the involvement of liver and adipose tissues in metformin actions on reducing hepatic steatosis and inflammation during obesity. C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to induce obesity-associated NAFLD and treated with metformin (150 mg/kg/d) orally for the last four weeks of HFD feeding. Compared with HFD-fed control mice, metformin-treated mice showed improvement in both glucose tolerance and insulin sensitivity. Also, metformin treatment caused a significant decrease in liver weight, but not adiposity. As indicated by histological changes, metformin treatment decreased hepatic steatosis, but not the size of adipocytes. In addition, metformin treatment caused an increase in the phosphorylation of liver AMP-activated protein kinase (AMPK), which was accompanied by an increase in the phosphorylation of liver acetyl-CoA carboxylase and decreases in the phosphorylation of liver c-Jun N-terminal kinase 1 (JNK1) and in the mRNA levels of lipogenic enzymes and proinflammatory cytokines. However, metformin treatment did not significantly alter adipose tissue AMPK phosphorylation and inflammatory responses. In cultured hepatocytes, metformin treatment increased AMPK phosphorylation and decreased fat deposition and inflammatory responses. Additionally, in bone marrow-derived macrophages, metformin treatment partially blunted the effects of lipopolysaccharide on inducing the phosphorylation of JNK1 and nuclear factor kappa B (NF-κB) p65 and on increasing the mRNA levels of proinflammatory cytokines. Taken together, these results suggest that metformin protects against obesity-associated NAFLD largely through direct effects on decreasing hepatocyte fat deposition and on inhibiting inflammatory responses in both hepatocytes and macrophages