225 research outputs found
Inhibition of endogenous SPARC enhances pancreatic cancer cell growth: modulation by FGFR1-III isoform expression
Interface modification of clay and graphene platelets reinforced epoxy nanocomposites: a comparative study
The interface between the matrix phase and dispersed phase of a composite plays a critical role in influencing its properties. However, the intricate mecha-nisms of interface are not fully understood, and polymer nanocomposites are no exception. This study compares the fabrication, morphology, and mechanical and thermal properties of epoxy nanocomposites tuned by clay layers (denoted as m-clay) and graphene platelets (denoted as m-GP). It was found that a chemical modification, layer expansion and dispersion of filler within the epoxy matrix resulted in an improved interface between the filler mate-rial and epoxy matrix. This was confirmed by Fourier transform infrared spectroscopy and transmission electron microscope. The enhanced interface led to improved mechanical properties (i.e. stiffness modulus, fracture toughness) and higher glass transition temperatures (Tg) compared with neat epoxy. At 4 wt% m-GP, the critical strain energy release rate G1c of neat epoxy improved by 240 % from 179.1 to 608.6 J/m2 and Tg increased from 93.7 to 106.4 �C. In contrast to m-clay, which at 4 wt%, only improved the G1c by 45 % and Tg by 7.1 %. The higher level of improvement offered by m-GP is attributed to the strong interaction of graphene sheets with epoxy because the covalent bonds between the carbon atoms of graphene sheets are much stronger than silicon-based clay
The effects of material formulation and manufacturing process on mechanical and thermal properties of epoxy/clay nanocomposites
A holistic study was conducted to investigate the combined effect of three different pre-mixing processes, namely mechanical mixing, ultrasonication and centrifugation, on mechanical and thermal properties of epoxy/clay nanocomposites reinforced with different platelet-like montmorillonite (MMT) clays (Cloisite Na+, Cloisite 10A, Cloisite 15 or Cloisite 93A) at clay contents of 3–10 wt%. Furthermore, the effect of combined pre-mixing processes and material formulation on clay dispersion and corresponding material properties of resulting composites was investigated using X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), flexural and Charpy impact tests, Rockwell hardness tests and differential scanning calorimetry (DSC). A high level of clay agglomeration and partially intercalated/exfoliated clay structures were observed regardless of clay type and content. Epoxy/clay nanocomposites demonstrate an overall noticeable improvement of up to 10 % in the glass transition temperature (Tg) compared to that of neat epoxy, which is interpreted by the inclusion of MMT clays acting as rigid fillers to restrict the chain mobility of epoxy matrices. The impact strength of epoxy/clay nanocomposites was also found to increase by up to 24 % with the addition of 3 wt% Cloisite Na+ clays. However, their flexural strength and hardness diminished when compared to those of neat epoxy, arising from several effects including clay agglomeration, widely distributed microvoids and microcracks as well as weak interfacial bonding between clay particles and epoxy matrices, as confirmed from TEM and SEM results. Overall, it is suggested that an improved technique should be used for the combination of pre-mixing processes in order to achieve the optimal manufacturing condition of uniform clay dispersion and minimal void contents
Nocturnin Expression Is Induced by Fasting in the White Adipose Tissue of Restricted Fed Mice
The relationship between circadian clocks and metabolism is intimate and complex and a number of recent studies have begun to reveal previously unknown effects of food and its temporal availability on the clock and the rhythmic transcriptome of peripheral tissues. Nocturnin, a circadian deadenylase, is expressed rhythmically in a wide variety of tissues, but we report here that Nocturnin expression is arrhythmic in epididymal white adipose tissue (eWAT) of mice housed in 12∶12 LD with ad libitum access to food. However, Nocturnin expression becomes rhythmic in eWAT of mice placed on restricted feeding. We show here that Nocturnin's rhythmic expression pattern is not dependent upon feeding, nor is it acutely induced by feeding in the liver or eWAT of ad libitum fed mice. However, Nocturnin is acutely induced by the absence of the expected meal in eWAT of restricted fed mice. A rise in cAMP levels also induces Nocturnin expression, suggesting that Nocturnin's induction in eWAT by fasting is likely mediated through the same pathways that activate lipolysis. Therefore, this suggests that Nocturnin plays a role in linking nutrient sensing by the circadian clock to lipid mobilization in the adipocytes
Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis
Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies
Synchronization of Circadian Per2 Rhythms and HSF1-BMAL1:CLOCK Interaction in Mouse Fibroblasts after Short-Term Heat Shock Pulse
Circadian rhythms are the general physiological processes of adaptation to daily environmental changes, such as the temperature cycle. A change in temperature is a resetting cue for mammalian circadian oscillators, which are possibly regulated by the heat shock (HS) pathway. The HS response (HSR) is a universal process that provides protection against stressful conditions, which promote protein-denaturation. Heat shock factor 1 (HSF1) is essential for HSR. In the study presented here, we investigated whether a short-term HS pulse can reset circadian rhythms. Circadian Per2 rhythm and HSF1-mediated gene expression were monitored by a real-time bioluminescence assay for mPer2 promoter-driven luciferase and HS element (HSE; HSF1-binding site)-driven luciferase activity, respectively. By an optimal duration HS pulse (43°C for approximately 30 minutes), circadian Per2 rhythm was observed in the whole mouse fibroblast culture, probably indicating the synchronization of the phases of each cell. This rhythm was preceded by an acute elevation in mPer2 and HSF1-mediated gene expression. Mutations in the two predicted HSE sites adjacent (one of them proximally) to the E-box in the mPer2 promoter dramatically abolished circadian mPer2 rhythm. Circadian Per2 gene/protein expression was not observed in HSF1-deficient cells. These findings demonstrate that HSF1 is essential to the synchronization of circadian rhythms by the HS pulse. Importantly, the interaction between HSF1 and BMAL1:CLOCK heterodimer, a central circadian transcription factor, was observed after the HS pulse. These findings reveal that even a short-term HS pulse can reset circadian rhythms and cause the HSF1-BMAL1:CLOCK interaction, suggesting the pivotal role of crosstalk between the mammalian circadian and HSR systems
The Comparison between Circadian Oscillators in Mouse Liver and Pituitary Gland Reveals Different Integration of Feeding and Light Schedules
The mammalian circadian system is composed of multiple peripheral clocks that are synchronized by a central pacemaker in the suprachiasmatic nuclei of the hypothalamus. This system keeps track of the external world rhythms through entrainment by various time cues, such as the light-dark cycle and the feeding schedule. Alterations of photoperiod and meal time modulate the phase coupling between central and peripheral oscillators. In this study, we used real-time quantitative PCR to assess circadian clock gene expression in the liver and pituitary gland from mice raised under various photoperiods, or under a temporal restricted feeding protocol. Our results revealed unexpected differences between both organs. Whereas the liver oscillator always tracked meal time, the pituitary circadian clockwork showed an intermediate response, in between entrainment by the light regimen and the feeding-fasting rhythm. The same composite response was also observed in the pituitary gland from adrenalectomized mice under daytime restricted feeding, suggesting that circulating glucocorticoids do not inhibit full entrainment of the pituitary clockwork by meal time. Altogether our results reveal further aspects in the complexity of phase entrainment in the circadian system, and suggest that the pituitary may host oscillators able to integrate multiple time cues
Targeting the cell cycle for cancer therapy
Most if not all neoplasias show a directly or indirectly deregulated cell cycle. Targeting its regulatory molecules, the cyclin-dependent kinases, as a therapeutic mode to develop new anticancer drugs, is being currently explored in both academia and pharmaceutical companies. The development of new compounds is being focused on the many features of the cell cycle with promising preclinical data in most fields. Moreover, a few compounds have entered clinical trials with excellent results maintaining the high hopes. Thus, although too early to provide a cell cycle target based new commercial drug, there is no doubt that it will be an excellent source of new anticancer compounds
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