Identification of Oxidative Stress Related Proteins as Biomarkers for Lung Cancer and Chronic Obstructive Pulmonary Disease in Bronchoalveolar Lavage

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis.     

Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

In vitro digestibility of phenolic compounds from edible fruits: could it be explained by chemometrics?

The health benefits of phenolic compounds depend on the ingested amount, molecular diversity and gastrointestinal digestibility. The phenolic profile of eight fruits (blackberry, blueberry, strawberry, raspberry, mulberry, pomegranate, green and red globe grapes) was chemometrically associated with their in vitro digestibility (oral, gastric, intestinal). Extractable phenols, flavonoids and anthocyanins strongly correlated with each other (r ≥ 0.84), proanthocyanidins with anthocyanins (r = 0.62) and hydrolysable phenols with both extractable phenols (r = 0.45) and proanthocyanidins (r = ?0.54). Two principal components explained 93% of the variance [61% (free‐phenols), 32% (bounded‐phenols)], and four clusters were confirmed by hierarchical analysis, based in their phenolic richness (CLT 1‐4: low to high) and molecular diversity. In vitro digestibility of extractable phenols and flavonoids was blackberry (CLT‐4)> raspberry (CLT‐2)> red grape (CLT‐1) related to their phenolic richness (r ≥ 0.96; P < 0.001), but anthocyanins’ digestibility was pH‐dependent. Chemometrics is useful to predict the in vitro digestibility of phenolic compounds in the assayed fruits.     

Relative Buoyancy Dominates Thermal-Like Flow Interaction along an Incline

This paper describes laboratory investigations of the motion between two fixed volumes of dense fluid (surge-type gravity currents) with different salt concentrations that interact above an incline in the presence of ambient stratification. The experiments include both large and small density contrasts between the interacting surges. Initially, the propagation of each fluid mass assumes a thermal-like nature, but then the lower density surge is quickly caught up by the denser fluid flow because of its higher velocity. There are two key process regarding the surge interaction. With a large density contrasting the fluid volumes, the denser flow moves to the front of the current as an intrusion with no mixing. With a small density difference, pronounced mixing occurs between the surges with the development of a homogeneous underflow. A simple energy parameterization is developed to evaluate the source conditions under which the different flow dynamics develop.     

Elastomeric Protein Bioactive Eutectogels for Topical Drug Delivery

Therapeutic deep eutectic solvents (THEDES) are an emerging family of eutectic mixtures gaining increasing interest in the biomedical space. The immobilization of THEDES into polymer networks allows bioactive eutectogels to expand their application scope to topical drug delivery. Herein, this work presents the first set of elastomeric eutectogels constructed by supporting a therapeutic eutectic system with skin permeation ability in a protein scaffold dynamically crosslinked by a natural polyphenol. In this ionic eutectic, gelatin undergoes gelation through an unexpected mechanism in striking contrast with classical hydrogels, which is herein thoroughly studied. Interestingly, the polyphenol controls the conformation of the protein structure, enabling tuning up the mechanical and viscoelastic behavior of the dynamic eutectogel networks from elastic to hyperelastic. The resultant protein eutectogels exhibit strain-hardening behavior, thermoreversible gel-to-sol transition, and excellent adhesive performance. Furthermore, these versatile materials retain the bioactivity of the liquid THEDES and favor skin occlusion, assisting the delivery of both hydrophilic and hydrophobic substances in ex vivo porcine skin in a time-dependent penetration process. These ultrastretchable eutectogels show new interplays between protein scaffolds and eutectic mixtures, paving the way for innovative therapeutic soft materials.     

Iron deficiency enhances bioactive phenolics in lemon juice

BACKGROUND This study was designed to describe the phenolic status of lemon juice obtained from fruits of lemon trees differing in iron (Fe) nutritional status. Three types of Fe(III) compound were used in the experiment, namely a synthetic chelate and two complexes derived from natural polymers of humic and lignine nature. RESULTS All three Fe(III) compounds were able to improve the Fe nutritional status of lemon trees, though to different degrees. This Fe(III) compound effect led to changes in the polyphenol content of lemon juice. Total phenolics were decreased (～33% average decrease) and, in particular, flavanones, flavones and flavonols were affected similarly. CONCLUSION Iron‐deficient trees showed higher phenolic contents than Fe(III) compound‐treated trees, though Fe deficiency had negative effects on the yield and visual quality of fruits. However, from a human nutritional point of view and owing to the health‐beneficial properties of their bioavailable phenolic compounds, the nutritional quality of fruits of Fe‐deficient lemon trees in terms of phenolics was higher than that of fruits of Fe(III) compound‐treated lemon trees. Moreover, diosmetin‐6,8‐di‐C‐glucoside in lemon juice can be used as a marker for correction of Fe deficiency in lemon trees. Copyright © 2011 Society of Chemical Industry     

CB1 cannabinoid receptor antagonist-induced opiate withdrawal in morphine-dependent rats

Recent reports have provided evidence of a link between the endogenous brain cannabinoid system and the endogenous central opioid systems. Here we report that the selective CB1 receptor antagonist SR 141716A induced behavioral and endocrine alterations associated with opiate withdrawal in morphine-dependent animals in a dose-dependent manner and that naloxone induced an opiate withdrawal syndrome in animals made cannabinoid-dependent by repeated administration of the potent cannabinoid agonist HU-210. Additionally CB1 and mu-opioid receptor mRNAs were co-localized in brain areas relevant for opiate withdrawal such as the nucleus accumbens, septum, dorsal striatum, the central amygdaloid nucleus and the habenular complex. These results suggest that CB1 cannabinoid receptors may play a role in the neuroadaptive processes associated with opiate dependence, and they lend further support for the hypothesis of a potential role of cannabinoid receptors in the neurobiological changes that culminate in drug addiction.     

Perspectives on allelopathy in mexican traditional agroecosystems: A case study in tlaxcala

Agroecosystems in Tlaxcala, Mexico, are surrounded by trees and water channels and have a great variety of cultivated and noncultivated plants. The main results of a study carried out on a traditional agroecosystem in Santa Inés, Tlaxcala are presented. Some ecological aspects of polycultures, plant covers (dry leaves ofAlnus firmifolia, Berula erecta, andJuncus sp.), and the allelopathic potential of crops and noncultivated plants (fresh and dry material) were analyzed. The main plants (trees, shrubs, and herbs) present in the agroecosystem were identified. The total number of weeds in plots where plant covers were added was reduced. The number of nodules ofRhizobium phaseoli and the production of bean and squash increased with plant covers. Corn, beans, and squash showed a clear allelopathic effect, as well asChenopodium murale, Tradescantia crassifolia, Melilotus indicus, andAmaranthus hybridus, among other weeds. The contribution of allelopathy in studies of traditional agroecosystems is of great importance for the management of species in space and time. Allelopathy can be the basis of biological control of pests and weeds and of the discovery of new useful substances.