Lipopolysaccharide From E. coli Increases Glutamate-Induced Disturbances of Calcium Homeostasis, the Functional State of Mitochondria, and the Death of Cultured Cortical Neurons

Lipopolysaccharide (LPS), a fragment of the bacterial cell wall, specifically interacting with protein complexes on the cell surface, can induce the production of pro-inflammatory and apoptotic signaling molecules, leading to the damage and death of brain cells. Similar effects have been noted in stroke and traumatic brain injury, when the leading factor of death is glutamate (Glu) excitotoxicity too. But being an amphiphilic molecule with a significant hydrophobic moiety and a large hydrophilic region, LPS can also non-specifically bind to the plasma membrane, altering its properties. In the present work, we studied the effect of LPS from Escherichia coli alone and in combination with the hyperstimulation of Glu-receptors on the functional state of mitochondria and Ca2+ homeostasis, oxygen consumption and the cell survival in primary cultures from the rats brain cerebellum and cortex. In both types of cultures, LPS (0.1–10 μg/ml) did not change the intracellular free Ca2+ concentration ([Ca2+]i) in resting neurons but slowed down the median of the decrease in [Ca2+]i on 14% and recovery of the mitochondrial potential (ΔΨm) after Glu removal. LPS did not affect the basal oxygen consumption rate (OCR) of cortical neurons; however, it did decrease the acute OCR during Glu and LPS coapplication. Evaluation of the cell culture survival using vital dyes and the MTT assay showed that LPS (10 μg/ml) and Glu (33 μM) reduced jointly and separately the proportion of live cortical neurons, but there was no synergism or additive action. LPS-effects was dependent on the type of culture, that may be related to both the properties of neurons and the different ratio between neurons and glial cells in cultures. The rapid manifestation of these effects may be the consequence of the direct effect of LPS on the rheological properties of the cell membrane.

Preparation of Cationic Amphiphilic Nanoparticles with Modified Chitosan Derivatives for Doxorubicin Delivery

Polymeric micelle-like nanoparticles have demonstrated effectiveness for the delivery of some poorly soluble or hydrophobic anticancer drugs. In this study, a hydrophobic moiety, deoxycholic acid (DCA) was first bonded on a polysaccharide, chitosan (CS), for the preparation of amphiphilic chitosan (CS-DCA), which was further modified with a cationic glycidyltrimethylammounium chloride (GTMAC) to form a novel soluble chitosan derivative (HT-CS-DCA). The cationic amphiphilic HT-CS-DCA was easily self-assembled to micelle-like nanoparticles about 200 nm with narrow size distribution (PDI 0.08–0.18). The zeta potential of nanoparticles was in the range of 14 to 24 mV, indicating higher positive charges. Then, doxorubicin (DOX), an anticancer drug with poor solubility, was entrapped into HT-CS-DCA nanoparticles. The DOX release test was performed in PBS (pH 7.4) at 37 °C, and the results showed that there was no significant burst release in the first two hours, and the cumulative release increased steadily and slowly in the following hours. HT-CS-DCA nanoparticles loaded with DOX could easily enter into MCF-7 cells, as observed by a confocal microscope. As a result, DOX-loaded HT-CS-DCA nanoparticles demonstrated a significant inhibition activity on MCF-7 growth without obvious cellular toxicity in comparison with blank nanoparticles. Therefore, the anticancer efficacy of these cationic HT-CS-DCA nanoparticles showed great promise for the delivery of DOX in cancer therapy.

A novel biosurfactant producing Kocuria rosea ABR6 as potential strain in oil sludge recovery and lubrication

Biosurfactants are amphiphilic molecules composed of a hydrophilic and hydrophobic moiety and had the ability to penetrate into different phases to reduce the surface tension. This features caused to oil recovery, lubrication and facilities of crude oil in pipeline. In current research Biosurfactant-producing strain was isolated from the storage tanks of the Isfahan Oil Refining Company in Iran, and screened by oil expansion test, droplet collapse, and surface tension reduction measurement. Hydrocarbon recovery from crude oil sludge was measured under constant conditions. The effect of factoring biosource lubrication on crude oil in pipelines was investigated in vitro. Also, the optimization of biosurfactant production in different conditions was measured as a single factor and using Response Surface Method (RSM). The best biosurfactant-producing bacterium was identified as Kocuria rosea ABR6, and its sequence was registered in the gene bank with access number of MK100469. Chemical analysis proved that the produced biosurfactant was a lipopeptide. 7% of crude oil was recovered from petroleum sludge by biosurfactant obtained from Kocuria rosea ABR6. Also, the speed of crude oil transfer in pipelines was upgraded as it could be said that for a certain distance the transfer time reduced from 64 to 35 s. The highest biosurfactant production was measured at pH 9, aeration rate of 120 rpm and 96 h after incubation. The use of biosurfactants produced by Kocuria rosea ABR6 is recommended to remove oil sludge and lubricate oil in pipelines recommended in the oil industry.

Fabrication of Humidity-Resistant Optical Fiber Sensor for Ammonia Sensing Using Diazo Resin-Photocrosslinked Films with a Porphyrin-Polystyrene Binary Mixture

Ammonia gas sensors were fabricated via layer-by-layer (LbL) deposition of diazo resin (DAR) and a binary mixture of tetrakis(4-sulfophenyl)porphine (TSPP) and poly(styrene sulfonate) (PSS) onto the core of a multimode U-bent optical fiber. The penetration of light transferred into the evanescent field was enhanced by stripping the polymer cladding and coating the fiber core. The electrostatic interaction between the diazonium ion in DAR and the sulfonate residues in TSPP and PSS was converted into covalent bonds using UV irradiation. The photoreaction between the layers was confirmed by UV-vis and Fourier transform infrared spectroscopy. The sensitivity of the optical fiber sensors to ammonia was linear when exposed to ammonia gases generated from aqueous ammonia solutions at a concentration of approximately 17 parts per million (ppm). This linearity extended up to 50 ppm when the exposure time (30 s) was shortened. The response and recovery times were reduced to 30 s with a 5-cycle DAR/TSPP+PSS (as a mixture of 1 mM TSPP and 0.025 wt% PSS in water) film sensor. The limit of detection (LOD) of the optimized sensor was estimated to be 0.31 ppm for ammonia in solution, corresponding to approximately 0.03 ppm of ammonia gas. It is hypothesized that the presence of the hydrophobic moiety of PSS in the matrix suppressed the effects of humidity on the sensor response. The sensor response was stable and reproducible over seven days. The PSS-containing U-bent fiber sensor also showed superior sensitivity to ammonia when examined alongside amine and non-amine analytes.

A Conserved Hydrophobic Moiety and Helix–Helix Interactions Drive the Self-Assembly of the Incretin Analog Exendin-4

Exendin-4 is a pharmaceutical peptide used in the control of insulin secretion. Structural information on exendin-4 and related peptides especially on the level of quaternary structure is scarce. We present the first published association equilibria of exendin-4 directly measured by static and dynamic light scattering. We show that exendin-4 oligomerization is pH dependent and that these oligomers are of low compactness. We relate our experimental results to a structural hypothesis to describe molecular details of exendin-4 oligomers. Discussion of the validity of this hypothesis is based on NMR, circular dichroism and fluorescence spectroscopy, and light scattering data on exendin-4 and a set of exendin-4 derived peptides. The essential forces driving oligomerization of exendin-4 are helix–helix interactions and interactions of a conserved hydrophobic moiety. Our structural hypothesis suggests that key interactions of exendin-4 monomers in the experimentally supported trimer take place between a defined helical segment and a hydrophobic triangle constituted by the Phe22 residues of the three monomeric subunits. Our data rationalize that Val19 might function as an anchor in the N-terminus of the interacting helix-region and that Trp25 is partially shielded in the oligomer by C-terminal amino acids of the same monomer. Our structural hypothesis suggests that the Trp25 residues do not interact with each other, but with C-terminal Pro residues of their own monomers.

2-((E)-2-((E)-4-Chloro-5-(2-((E)-5-methoxy-3,3-dimethyl-1-(3-phenylpropyl)indolin-2-ylidene) ethylidene)-1,1-dimethyl-1,2,5,6-tetrahydropyridin-1-ium-3-yl)vinyl)-5-methoxy-3,3-dimethyl-1-(3-phenylpropyl)-3H-indol-1-ium

A heptamethine fluorophore, ERB-60, has been synthesized efficiently in four steps in a good yield. The structure of this fluorophore consists of an electron-donating group (methoxy), a hydrophobic moiety (phenylpropyl) with a rotatable bond, a quaternary ammonium fragment, and indolium rings at the terminal ends connected via polymethine chain. All these inherent chemical features fine-tuned the optical properties of the fluorophore. This compound was characterized by both 1H NMR, 13C NMR and mass spectra. The optical properties, including molar absorptivity, fluorescence, Stokes’s shift, and quantum yield, were measured in different solvents such as DMSO, DMF, MeCN, i-PrOH, MeOH, and H2O. The wavelengths of maximum absorbance of ERB-60 were found to be in the range of 745–770 nm based on the solvents used. In decreasing order, the maximum wavelength of absorbance of ERB-60 in the tested solvents was DMSO > DMF > i-PrOH > MeOH > MeCN > H2O while the decreasing order of the extinction coefficient was found to be MeCN > MeOH > DMSO > i-PrOH > H2O > DMF. ERB-60 was found to be more photostable than IR-786 iodide, a commercially available dye, and brighter than the FDA-approved dye, indocyanine green (ICG).

Hydrophobic Tagging-Mediated Degradation of Transcription Coactivator SRC-1

Steroid receptor coactivator-1 (SRC-1) is a transcription coactivator playing a pivotal role in mediating a wide range of signaling pathways by interacting with related transcription factors and nuclear receptors. Aberrantly elevated SRC-1 activity is associated with cancer metastasis and progression, and therefore, suppression of SRC-1 is emerging as a promising therapeutic strategy. In this study, we developed a novel SRC-1 degrader for targeted degradation of cellular SRC-1. This molecule consists of a selective ligand for SRC-1 and a bulky hydrophobic group. Since the hydrophobic moiety on the protein surface could mimic a partially denatured hydrophobic region of a protein, SRC-1 could be recognized as an unfolded protein and experience the chaperone-mediated degradation in the cells through the ubiquitin–proteasome system (UPS). Our results demonstrate that a hydrophobic-tagged chimeric molecule is shown to significantly reduce cellular levels of SRC-1 and suppress cancer cell migration and invasion. Together, these results highlight that our SRC-1 degrader represents a novel class of therapeutic candidates for targeting cancer metastasis. Moreover, we believe that the hydrophobic tagging strategy would be widely applicable to develop peptide-based protein degraders with enhanced cellular activity.

Xanthone: Potential Acetylcholinesterase Inhibitor for Alzheimer's Disease Treatment

: Alzheimer's disease is a neurodegenerative disorder that results in progressive and irreversible central nervous system impairment, which has become one of the severe issues recently. The most successful approach of Alzheimer’s treatment is the administration of cholinesterase inhibitors to prevent the hydrolysis of acetylcholine and subsequently improve the cholinergic postsynaptic transmission. This review highlights a class of heterocycle, namely xanthone and its remarkable acetylcholinesterase inhibitory activities. Naturally occurring xanthones, including oxygenated, prenylated, pyrano and glycosylated xanthones exhibited promising inhibition effects towards acetylcholinesterase. Interestingly, synthetic xanthone derivatives with complex substituents such as alkyl, pyrrolidine, piperidine and morpholine have shown greater acetylcholinesterase inhibition activities. Structure-activity relationship of xanthones revealed that the type and position of substituent(s) attached to the xanthone moiety influenced their acetylcholinesterase inhibition activities where hydrophobic moiety will lead to an improved activity by contributing the π-π interactions, as well as the hydroxy substituent(s) by forming hydrogen-bond interactions. Thus, further studies including quantitative structure-activity relationship, in vivo and clinical validation studies are crucial for the development of xanthones into novel anti-Alzheimer's disease drugs.

Simultaneous Adsorption of Cation and Anion by Thermosensitive Hydrogels

Simultaneous usage of cationic and anionic thermosensitive hydrogels was shown to positively contribute to adsorption of heavy metal ions. The potential capacity for recovering heavy metal ions from an aqueous solution was enhanced by incorporating relatively hydrophobic moiety to the hydrogels, which was ascribed to the increase in the desorption on elevating the temperature over the lower critical swelling temperature (LCST). N-tert-butylacrilamide was added into the hydrogels to increase its desorption potential. The addition of N-tert-butylacrylamide does not significantly affect hydrogels’ adsorption ability. Moreover, the adsorption-desorption cycle was not diminished by repeating the temperature swing above the critical temperature at which the volume phase transition was induced.