Metal Binding Antimicrobial Peptides in Nanoparticle Bio-functionalization: New Heights in Drug Delivery and Therapy

Probiotics and Antimicrobial Proteins - Peptides are considered very important due to the diversity expressed through their amino acid sequence, structure variation, large spectrum, and their...     

Effects of curcumin on bleomycin-induced apoptosis in human malignant testicular germ cells

Testicular cancer is the most common cancer among young men of reproductive age. Bleomycin is a frequently used drug for the treatment of several malignancies and is part of the chemotherapy protocols in testicular cancer. Bleomycin causes an increase in oxidative stress which has been shown to induce apoptosis in cancer cells. Curcumin (diferuloylmethane), an active component of the spice turmeric, has attracted interest because of its anti-inflammatory and chemopreventive activities. However, no study has been carried out so far to elucidate its interaction with bleomycin in testicular cancer cells. In this study, we investigated the effects of curcumin and bleomycin on apoptosis signalling pathways and compared the effects of bleomycin with H₂O₂ which directly produces reactive oxygen species. We measured apoptosis markers such as caspase-3, caspase-8, and caspase-9 activities and Bcl-2, Bax, and Cyt-c levels in NCCIT cells incubated with curcumin (5 μM), bleomycin (120 μg/ml), bleomycin + curcumin, H₂O₂ (35 μM), and H₂O₂ + curcumin for 72 h. Curcumin, bleomycin, and H₂O₂ caused apoptosis indicated as increases in caspase-3, caspase-8, and caspase-9 activities and Bax and cytoplasmic Cyt-c levels and a decrease in Bcl-2 level. Concurrent use of curcumin with bleomycin decreased caspase activities and Bax and Cyt-c levels compared to their separate effects in NCCIT cells. Our findings suggest that concurrent use of curcumin during chemotherapy in testis cancer should be avoided due to the inhibitory effect of curcumin on bleomycin-induced apoptosis.     

Patterns of time since last meal revealed by sparse PCA in an observational LC–MS based metabolomics study

In metabolomics studies, liquid chromatography mass spectrometry (LC–MS) provides comprehensive information on biological samples. However, extraction of few relevant metabolites from this large and complex data is cumbersome. To resolve this issue, we have employed sparse principal component analysis (SPCA) to capture the underlying patterns and select relevant metabolites from LC–MS plasma profiles. The study involves a small pilot cohort with 270 subjects where each subject’s time since last meal (TSLM) has been recorded prior to plasma sampling. Our results have demonstrated that both PCA and SPCA can capture the TSLM patterns. Nevertheless, SPCA provides more easily interpretable loadings in terms of selection of relevant metabolites, which are identified as amino acids and lyso-lipids. This study demonstrates the utility of SPCA as a pattern recognition and variable selection tool in metabolomics. Furthermore, amino acids and lyso-lipids are determined as dominating compounds in response to TSLM.     

Development and verification of a three-dimensional (3D) breast cancer tumor model composed of circulating tumor cell (CTC) subsets

Molecular Biology Reports - Breast cancer is one of the most common cancer types among women in which early tumor invasion leads to metastases and death. EpCAM (epithelial cellular adhesion...     

Homology in Trivaline Complex Formation with dsDNA and ssRNA

Abstract

It has been shown by the equilibrium dialysis that at a polyU concentration above the “critical” one, the complete polymer saturation with trivaline reaches approximately 0.7 trivaline molecules per one phosphate group. i.e. at these conditions peptide dimer occupies on polyU a site of three bases (phosphates) in length. The trivaline complex with polyU at a concentration lower than the “critical” one does not reveal any noticeable fluorescence, but has rather significant positive linear dichroism at 265 and 330 nm. The trivaline-nucleic acids complex has a significant fluorescence at any dsDNA concentration while with polyU it is only so at a concentration above the “critical” one. Electron microscopy has shown that at a rather high concentration of dsDNA molecules in solution a “biduplex” structure undergoes an additional stage of compaction, during which the extended particles more than 30 nm in diameter are formed.

Schematic models for the trivaline complexes and compact structures with dsDNA and ssRNA are propose     

Synthesis and antibacterial activity of novel phosphonium salts on the basis of pyridoxine

A series of 13 phosphonium salts on the basis of pyridoxine derivatives were synthesized and their antibacterial activity against clinically relevant strains was tested in vitro. All compounds were almost inactive against gram-negative bacteria and exhibited structure-dependent activity against gram-positive bacteria. A crucial role of ketal protection group in phosphonium salts for their antibacterial properties was demonstrated. Among synthesized compounds 5,6-bis[triphenylphosphonio(methyl)]-2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine dichloride (compound 20) was found to be the most effective towards Staphylococcus aureus and Staphylococcus epidermidis strains (MIC 5 μg/ml). The mechanism of antibacterial activity of this compound probably involves cell penetration and interaction with genomic and plasmid DNA.     

Trisubstituted and tetrasubstituted pyrazolines as a novel class of cell-growth inhibitors in tumor cells with wild type p53

Derivatives with scaffolds of 1,3,5-tri-substituted pyrazoline and 1,3,4,5-tetra-substituted pyrazoline were synthesized and tested for their inhibitory effects versus the p53^+/+ HCT116 and p53^?/? H1299 human tumor cell lines. Several compounds were active against the two cell lines displaying IC₅₀ values in the low micromolar range with a clearly more pronounced effect on the p53^+/+ HCT116 cells. The compound class shows excellent developability due to the modular synthesis, allowing independent optimization of all three to four key substituents to improve the properties of the molecules.     

Climate Change Increases Drought Stress of Juniper Trees in the Mountains of Central Asia

Assessments of climate change impacts on forests and their vitality are essential for semi-arid environments such as Central Asia, where the mountain regions belong to the globally important biodiversity hotspots. Alterations in species distribution or drought-induced tree mortality might not only result in a loss of biodiversity but also in a loss of other ecosystem services. Here, we evaluate spatial trends and patterns of the growth-climate relationship in a tree-ring network comprising 33 juniper sites from the northern Pamir-Alay and Tien Shan mountain ranges in eastern Uzbekistan and across Kyrgyzstan for the common period 1935–2011. Junipers growing at lower elevations are sensitive to summer drought, which has increased in intensity during the studied period. At higher elevations, juniper growth, previously favored by warm summer temperatures, has in the recent few decades become negatively affected by increasing summer aridity. Moreover, response shifts are observed during all seasons. Rising temperatures and alterations in precipitation patterns during the past eight decades can account for the observed increase in drought stress of junipers at all altitudes. The implications of our findings are vital for the application of adequate long-term measures of ecosystem conservation, but also for paleo-climatic approaches and coupled climate-vegetation model simulations for Central Asia.     

Thermally induced cyclization of L‐isoleucyl‐L‐alanine in solid state: Effect of dipeptide structure on reaction temperature and self‐assembly

Thermal treatment of short‐chain oligopeptides is able to initiate the process of their self‐assembly with the formation of organic nanostructures with unique properties. On the other hand, heating can lead to a chemical reaction with the formation of new substances with specific properties and ability to form structures with different morphology. Therefore, in order to have a desired process, researcher needs to find its temperature range. In the present work, cyclization of _L‐isoleucyl‐_L‐alanine dipeptide in the solid state upon heating was studied. Kinetic parameters of this reaction were estimated within the approaches of the nonisothermal kinetics. The correlation between side chain structure of dipeptides and temperature of their cyclization in the solid state was found for the first time. This correlation may be used to predict the temperature, at which dipeptide self‐assembly changes to chemical reaction. The differences in self‐assembly of linear and cyclic dipeptides were demonstrated using atomic force microscopy. The effect of dipeptide concentration in a source solution and an organic solvent used on self‐assembly of dipeptides was shown. The new information obtained on the thermal properties and self‐assembly of linear and cyclic forms of _L‐isoleucyl‐_L‐alanine may be useful for the design of new nanomaterials based on oligopeptides, as well as for the synthesis of cyclic oligopeptides.     

iASPP protects the heart from ischemia injury by inhibiting p53 expression and cardiomyocyte apoptosis

Currently, there remains a great need to elucidate the molecular mechanism of acute myocardial infarction in order to facilitate the development of novel therapy. Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is a member of the ASPP family proteins and an evolutionarily preserved inhibitor of p53 that is involved in many cellular processes, including apoptosis of cancer cells. The purpose of this study was to investigate the possible role of iASPP in acute myocardial infarction. The protein level of iASPP was markedly reduced in the ischemic hearts in vivo and hydrogen peroxide-exposed cardiomyocytes in vitro. Overexpression of iASPP reduced the infarct size and cardiomyocyte apoptosis of mice subjected to 24 h of coronary artery ligation. Echocardiography showed that cardiac function was improved as indicated by the increase in ejection fraction and fractional shortening. In contrast, knockdown of iASPP exacerbated cardiac injury as manifested by impaired cardiac function, increased infarct size, and apoptosis rate. Mechanistically, overexpression of iASPP inhibited, while knockdown of iASPP increased the expressions of p53 and Bax, the key regulators of apoptosis. Taken together, our results suggested that iASPP is an important regulator of cardiomyocyte apoptosis, which represents a potential target in the therapy of myocardial infarction.