Doxorubicin and beta-lapachone release and interaction with micellar core materials: experiment and modeling

Polymer micelles with two different core-forming blocks, poly(d,l -lactide) (PLA) and poly(epsilon-caprolactone) (PCL), but the same coronal material, poly(ethylene glycol) (PEG), were investigated in this study as nanoscopic drug carriers. The release of two different drugs, doxorubicin (DOX) and beta-lapachone (beta-lap), from PEG(5k)-b-PCL(5k) and PEG(5k)-b-PLA(5k) micelles was studied at pH 5.0 and 7.4. Mathematical solutions of both Higuchi's model and Fickian diffusion equations were utilized to elucidate the differences between the micelle core materials for the two drugs. The neutral and smaller of the two drugs tested, beta-lap, demonstrated faster, pH-independent release, suggesting that no substantial changes occurred in either micelle core at lower pH. In contrast, the release rate of DOX was found to noticeably increase at lower pH with a larger cumulative amount of drug released. Different core materials were shown to have considerable influence on the release kinetics of both drugs: in both cases, the more hydrophobic PCL core showed slower drug release rates compared with the less hydrophobic PLA core.     

Protein expression in sputum of smokers and chronic obstructive pulmonary disease patients: a pilot study by CapLC-ESI-Q-TOF

The current report describes the use of CapLC-ESI-Q/TOF-MS for investigating the proteome profiles of hypertonic saline-induced sputum samples from 56 smokers. The severity of their lung disease ranged from normal (healthy smokers) to chronic bronchitis, chronic obstructive pulmonary disease (COPD), and COPD with emphysema. This pilot study examined the hypothesis that there were distinct differences in protein expression profiles that were related to the phenotype and cigarette smoking illness severity. A total of 203 unique proteins were identified. These may represent the most highly expressed proteins in induced sputum. Our results provide evidence that different proteins are expressed, as the disease progresses from health to more advanced stages, and support our contention that a proteomic approach would be beneficial in discovering selective molecules linked to specific COPD stages.     

Comparative proteomic analysis of chronic myelogenous leukemia cells: inside the mechanism of imatinib resistance

Imatinib is the first molecular targeted therapy that has shown clinical success, but imatinib acquired resistance, although a rare event, is critical during the therapy of chronic myelogenous leukaemia (CML). With the aim of better understanding the molecular mechanisms accompanying acquisition of resistance to this drug, a comparative proteomic approach was undertaken on CML cell lines LAMA 84 S (imatinib sensitive) and LAMA 84 R (imatinib resistant). Forty-four differentially expressed proteins were identified and categorized into five main functional classes: (I) heat shock proteins and chaperones; (II) nucleic acid interacting proteins (binding/synthesis/stability); (III) structural proteins, (IV) cell signaling, and (V) metabolic enzymes. Several heat shock proteins known to complex Bcr-Abl were overexpressed in imatinib resistant cells, showing a possible involvement of these proteins in the mechanism of resistance. HnRNPs also resulted in being up-regulated in imatinib resistant cells. These proteins have been shown to be strongly and directly related to Bcr-Abl activity. To our knowledge, this is the first direct proteomic comparison of imatinib sensitive/resistant CML cell lines.     

Identification of the Channelrhodopsin Genes in the Green and Cryptophytic Algae from the White and Black Seas

Biochemistry (Moscow) - Due to the unique capability of modulating cell membrane potential upon photoactivation, channelrhodopsins of green (Chlorophyta) and cryptophytic (Cryptophyta) algae are...     

Effects of the Cc2d1a/Freud-1 Knockdown in the Hippocampus of BTBR Mice on the Autistic-Like Behavior,Expression of Serotonin 5-HT1A and D2 Dopamine Receptors,and CREB and NF-kB Intracellular Signaling

Biochemistry (Moscow) - The mechanisms of autism are of extreme interest due to the high prevalence of this disorder in the human population. In this regard, special attention is given to the...     

Structural Insight into Evolution of the Quinone Binding Site in Complex II

Biochemistry (Moscow) - The Complex II family encompasses membrane bound succinate:quinones reductases and quinol:fumarate reductases that catalyze interconversion of succinate and fumarate coupled...     

Cryptophytes of Lake Shira (Khakassia,Russia): explosive growth during breakdown of meromixis

Hydrobiologia - We conducted a monitoring study on the dynamics of the abundance, biomass, and vertical distribution of the cryptophyte population in meromictic saline Lake Shira (90.11 E,...     

Genetic Improvement in <i>Juglans mandshurica</i> and Its Uses in China: Current Status and Future Prospects

Juglans mandshurica is an economically and ecologically valuable species that is used for various construction purposes, making luxurious furniture, as food and sources of medicinal substances and landscaping because of its excellent wood, edible fruits and rich in various types of chemical compounds. In the past few decades, several genetic improvements of J. mandshurica were made, with a focus on the selection of improved varieties and on breeding technology. Many elite provenances and families were selected based on growth traits or wood properties. In recent years, with the increasing demand for high-quality seedlings in Chinese forestry production, the breeding goals of genetic improvement for J. mandshurica were redefined to include other traits, such as fruit yield and contents of medicinal component. However, the improvement processes were still slow due to the long breeding cycle and the limited use of advanced breeding technologies, resulting in the selection of fewer improved varieties. In this review, we summarized the research progresses on genetic improvements of J. mandshurica and other related works, and discussed research gaps and suggested future directions for genetic improvement of the species. The review provides valuable insight for the selection of improved varieties and production of excellent germplasms.     

Photosynthetic performance in cyanobacteria with increased sulphide tolerance: an analysis comparing wild-type and experimentally derived strains

Sulphide is proposed to have influenced the evolution of primary stages of oxygenic photosynthesis in cyanobacteria. However, sulphide is toxic to most of the species of this phylum, except for some sulphide-tolerant species showing various sulphide-resistance mechanisms. In a previous study, we found that this tolerance can be induced by environmental sulphidic conditions, in which two experimentally derived strains with an enhanced tolerance to sulphide were obtained from Microcystis aeruginosa, a sensitive species, and Oscillatoria, a sulphide-tolerant genus. We have now analysed the photosynthetic performance of the wild-type and derived strains in the presence of sulphide to shed light on the characteristics underlying the increased tolerance. We checked whether the sulphide tolerance was a result of higher PSII sulphide resistance and/or the induction of sulphide-dependent anoxygenic photosynthesis. We observed that growth, maximum quantum yield, maximum electron transport rate and photosynthetic efficiency in the presence of sulphide were less affected in the derived strains compared to their wild-type counterparts. Nevertheless, in ¹⁴C photoincoporation assays, neither Oscillatoria nor M. aeruginosa exhibited anoxygenic photosynthesis using sulphide as an electron donor. On the other hand, the content of photosynthetic pigments in the derived strains was different to that observed in the wild-type strains. Thus, an enhanced PSII sulphide resistance appears to be behind the increased sulphide tolerance displayed by the experimentally derived strains, as observed in most natural sulphide-tolerant cyanobacterial strains. However, other changes in the photosynthetic machinery cannot be excluded.