Sensitivity to Cisplatin in Head and Neck Cancer Cells Is Significantly Affected by Patient-Derived Cancer-Associated Fibroblasts

Cancer-associated fibroblasts (CAFs) are one of the most abundant and critical components of the tumor stroma. CAFs can impact many important steps of cancerogenesis and may also influence treatment resistance. Some of these effects need the direct contact of CAFs and cancer cells, while some involve paracrine signals. In this study, we investigated the ability of head and neck squamous cell carcinomas (HNSCC) patient-derived CAFs to promote or inhibit the colony-forming ability of HNSCC cells. The effect of cisplatin on this promoting or inhibiting influence was also studied. The subsequent analysis focused on changes in the expression of genes associated with cancer progression. We found that cisplatin response in model HNSCC cancer cells was modified by coculture with CAFs, was CAF-specific, and different patient-derived CAFs had a different “sensitizing ratio”. Increased expression of VEGFA, PGE2S, COX2, EGFR, and NANOG in cancer cells was characteristic for the increase of resistance. On the other hand, CCL2 expression was associated with sensitizing effect. Significantly higher amounts of cisplatin were found in CAFs derived from patients who subsequently experienced a recurrence. In conclusion, our results showed that CAFs could promote and/or inhibit colony-forming capability and cisplatin resistance in HNSCC cells via paracrine effects and subsequent changes in gene expression of cancer-associated genes in cancer cells.     

A large-displacement 65Pb(Mg1/3Nb2/3)O3–35PbTiO3/Pt bimorph actuator prepared by screen printing

In this paper we present a novel approach to preparing large-displacement 65Pb(Mg_1/3Nb_2/3)O₃–35PbTiO₃/Pt (65/35 PMN–PT/Pt) bimorph actuators. These “substrate-free”, bending-type actuators were prepared by screen-printing the 65/35 PMN–PT and Pt thick-film pastes as the electrodes on alumina substrates. After this screen printing and the subsequent firing the 65/35 PMN–PT/Pt composites were peeled off from the substrates. Displacements of nearly 100 μm at 18 V were achieved for actuators with dimensions of 1.8 cm × 2.5 mm × 50 μm for the 65/35 PMN–PT layer. The normalized displacement (the displacement per unit length) was 40 μm/cm at 18 V. The experimental results together with a computation procedure were used to obtain the material parameters for a finite-element analysis of the 65/35 PMN–PT/Pt bimorph actuators.     

融合颜色相关性和纹理差异的阴影检测方法

在雨天交通视频中,车辆同时受阴影和水汽拖尾的干扰。为此,在分析目标车辆、路面、阴影和水汽拖尾区域特性的基础上,提出一种融合颜色相关性和纹理差异的阴影检测方法。由当前点与背景点的HIS向量点积测量颜色相关程度,检测出车辆目标和水汽拖尾区域,利用当前区域和背景区域的纹理差异区分深色车辆和阴影。实验结果表明,该方法能较好地检测雨天交通视频中运动车辆的投射阴影,且能有效去除水汽拖尾,从而保证车辆的正确分割。     

Age effects on social cognition: Faces tell a different story.

The authors administered social cognition tasks to younger and older adults to investigate age-related differences in social and emotional processing. Although slower, older adults were as accurate as younger adults in identifying the emotional valence (i.e., positive, negative, or neutral) of facial expressions. However, the age difference in reaction time was largest for negative faces. Older adults were significantly less accurate at identifying specific facial expressions of fear and sadness. No age differences specific to social function were found on tasks of self-reference, identifying emotional words, or theory of mind. Performance on the social tasks in older adults was independent of performance on general cognitive tasks (e.g., working memory) but was related to personality traits and emotional awareness. Older adults also showed more intercorrelations among the social tasks than did the younger adults. These findings suggest that age differences in social cognition are limited to the processing of facial emotion. Nevertheless, with age there appears to be increasing reliance on a common resource to perform social tasks, but one that is not shared with other cognitive domains. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Identification of Bacterial Membrane Selectivity of Romo1-Derived Antimicrobial Peptide AMPR-22 via Molecular Dynamics

The abuse or misuse of antibiotics has caused the emergence of extensively drug-resistant (XDR) bacteria, rendering most antibiotics ineffective and increasing the mortality rate of patients with bacteremia or sepsis. Antimicrobial peptides (AMPs) are proposed to overcome this problem; however, many AMPs have attenuated antimicrobial activities with hemolytic toxicity in blood. Recently, AMPR-11 and its optimized derivative, AMPR-22, were reported to be potential candidates for the treatment of sepsis with a broad spectrum of antimicrobial activity and low hemolytic toxicity. Here, we performed molecular dynamics (MD) simulations to clarify the mechanism of lower hemolytic toxicity and higher efficacy of AMPR-22 at an atomic level. We found four polar residues in AMPR-11 bound to a model mimicking the bacterial inner/outer membranes preferentially over eukaryotic plasma membrane. AMPR-22 whose polar residues were replaced by lysine showed a 2-fold enhanced binding affinity to the bacterial membrane by interacting with bacterial specific lipids (lipid A or cardiolipin) via hydrogen bonds. The MD simulations were confirmed experimentally in models that partially mimic bacteremia conditions in vitro and ex vivo. The present study demonstrates why AMPR-22 showed low hemolytic toxicity and this approach using an MD simulation would be helpful in the development of AMPs.     

CDDO-Me Attenuates Clasmatodendrosis in CA1 Astrocyte by Inhibiting HSP25-AKT Mediated DRP1-S637 Phosphorylation in Chronic Epilepsy Rats

Clasmatodendrosis is one of the irreversible astroglial degeneration, which is involved in seizure duration and its progression in the epileptic hippocampus. Although sustained heat shock protein 25 (HSP25) induction leads to this autophagic astroglial death, dysregulation of mitochondrial dynamics (aberrant mitochondrial elongation) is also involved in the pathogenesis in clasmatodendrosis. However, the underlying molecular mechanisms of accumulation of elongated mitochondria in clasmatodendritic astrocytes are elusive. In the present study, we found that clasmatodendritic astrocytes showed up-regulations of HSP25 expression, AKT serine (S) 473 and dynamin-related protein 1 (DRP1) S637 phosphorylations in the hippocampus of chronic epilepsy rats. 2-Cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me; bardoxolone methyl or RTA 402) abrogated abnormal mitochondrial elongation by reducing HSP25 upregulation, AKT S473- and DRP1 S637 phosphorylations. Furthermore, HSP25 siRNA and 3-chloroacetyl-indole (3CAI, an AKT inhibitor) abolished AKT-DRP1-mediated mitochondrial elongation and attenuated clasmatodendrosis in CA1 astrocytes. These findings indicate that HSP25-AKT-mediated DRP1 S637 hyper-phosphorylation may lead to aberrant mitochondrial elongation, which may result in autophagic astroglial degeneration. Therefore, our findings suggest that the dysregulation of HSP25-AKT-DRP1-mediated mitochondrial dynamics may play an important role in clasmatodendrosis, which would have implications for the development of novel therapies against various neurological diseases related to astroglial degeneration.     

Cancer Cell Response to Anthracyclines Effects: Mysteries of the Hidden Proteins Associated with These Drugs

A comprehensive proteome map of T-lymphoblastic leukemia cells and its alterations after daunorubicin, doxorubicin and mitoxantrone treatments was monitored and evaluated either by paired comparison with relevant untreated control and using multivariate classification of treated and untreated samples. With the main focus on early time intervals when the influence of apoptosis is minimized, we found significantly different levels of proteins, which corresponded to 1%–2% of the total amount of protein spots detected. According to Gene Ontology classification of biological processes, the highest representation of identified proteins for all three drugs belong to metabolic processes of proteins and nucleic acids and cellular processes, mainly cytoskeleton organisation and ubiquitin-proteasome pathway. Importantly, we observed significant proportion of changes in proteins involved in the generation of precursor metabolites and energy typical for daunorubicin, transport proteins participating in response to doxorubicin and a group of proteins of immune system characterising response to mitoxantrone. Both a paired comparison and the multivariate evaluation of quantitative data revealed daunorubicin as a distinct member of the group of anthracycline/anthracenedione drugs. A combination of identified drug specific protein changes, which may help to explain anti-cancer activity, together with the benefit of blocking activation of adaptive cancer pathways, presents important approaches to improving treatment outcomes in cancer.