To be or not to be cell autonomous? Autophagy says both.

Although cells are a part of the whole organism, classical dogma emphasizes that individual cells function autonomously. Many physiological and pathological conditions, including cancer, and metabolic and neurodegenerative diseases, have been considered mechanistically as cell-autonomous pathologies, meaning those that damage or defect within a selective population of affected cells suffice to produce disease. It is becoming clear, however, that cells and cellular processes cannot be considered in isolation. Best known for shuttling cytoplasmic content to the lysosome for degradation and repurposing of recycled building blocks such as amino acids, nucleotides, and fatty acids, autophagy serves a housekeeping function in every cell and plays key roles in cell development, immunity, tissue remodeling, and homeostasis with the surrounding environment and the distant organs. In this review, we underscore the importance of taking interactions with the microenvironment into consideration while addressing the cell autonomous and non-autonomous functions of autophagy between cells of the same and different types and in physiological and pathophysiological situations.

Fine-tuning autophagy: from transcriptional to posttranslational regulation.

Macroautophagy (hereafter called autophagy) is a vacuolar lysosomal pathway for degradation of intracellular material in eukaryotic cells. Autophagy plays crucial roles in tissue homeostasis, in adaptation to stress situations, and in immune and inflammatory responses. Alteration of autophagy is associated with cancer, diabetes and obesity, cardiovascular disease, neurodegenerative disease, autoimmune disease, infection, and chronic inflammatory disease. Autophagy is controlled by autophagy-related (ATG) proteins that act in a coordinated manner to build up the initial autophagic vacuole named the autophagosome. It is now known that the activities of ATG proteins are modulated by posttranslational modifications such as phosphorylation, ubiquitination, and acetylation. Moreover, transcriptional and epigenetic controls are involved in the regulation of autophagy in stress situations. Here we summarize and discuss how posttranslational modifications and transcriptional and epigenetic controls regulate the involvement of autophagy in the proteostasis network.

Potentiation of the bactericidal activity of Harungana madagascariensis Lam. ex Poir. (Hypericaceae) leaf extract against oral bacteria using poly (D, L-lactide-co-glycolide) nanoparticles: in vitro study.

Harungana madagascariensis Lam. ex Poir. (Hypericaceae) is known to have biological properties with mainly antibacterial, antifungal, and antiviral effects. The objective of this study was to investigate the in vitro bactericidal activity of the ethyl acetate H. madagascariensis leaf extract (HLE) on the main oral bacterial strains largely implicated in dental caries and gingivitis infections, and the possibility of potentialization of HLE antibacterial effects using the poly (D,L-lactide-co-glycolide) nanoparticles (PLG-NP). The microdilution technique and the interfacial polymer deposition following the solvent diffusion method were used to investigate the in vitro bactericidal activity of ethyl acetate HLE and to prepare nanoparticles, respectively. HLE showed significant bactericidal effects against the bacterial strains tested, with minimal bactericidal concentration (MBC) to 5 x 10(2) mg/l or less, except for Lactobacillus casei with 7.5 x 10(2) mg/l. With the HLE incorporated into PLG nanoparticles (HLE-PLG-NP), we observed diminution of the bactericidal concentration compared to HLE, the upper MBC being of 1.875 x 10(2) mg/l. Incorporation of the HLE into a colloidal carrier optimized its antibacterial performance.

Penetration kinetics of xanthotoxin across human skin and stratum corneum / 药学学报

<p><b>AIM</b>To investigate the penetration kinetics of xanthotoxin in human skin and stratum corneum.</p><p><b>METHODS</b>The penetration experiments were accomplished by the deposit of ethanolic xanthotoxin solution onto human skin and stratum corneum mounted on Franz cells. The diffused xanthotoxin in the receptor solution (1.4% human serum albumin) and the retained amount in the skin and in the stratum corneum after 24 h exposure were quantified by using high performance liquid chromatography.</p><p><b>RESULTS</b>Xanthotoxin flux was increased with the concentration deposited onto the human skin, and when the concentration is above 2.5 mg x mL(-1), there is no influence on the xanthotoxin flux. Similar results were obtained from the stratum corneum. And the peak time for the flux in the stratum corneum was preceded about 6 h earlier than that of the whole human skin. The retained xanthotoxin amount after 24 h exposure in the skin and in the stratum corneum increased according to the concentration deposited and has the tendency to saturate. The lag time of ethanolic xanthotoxin solution in the whole human skin is significantly higher than that in the stratum corneum (P < 0.05).</p><p><b>CONCLUSION</b>The characteristics of penetration kinetics of xanthotoxin will provide the information for concentration choice of topical formulation and give a reference for ultra violet A (UVA) irradiation time confirmation.</p>

Vitamins C and E reverse effect of herbicide-induced toxicity on human epidermal cells HaCaT: a biochemometric approach.

The purpose of this study was to investigate and compare the cytotoxicity of glyphosate alone or included in Roundup 3 plus modulated by the cytoprotective effects of additional antioxidants such as Vitamin C and Vitamin E on the human keratinocytes cell line HaCaT. An experimental design which allows to minimize the number of experiments was carried out to determine the optimal conditions for cytoprotection against herbicide-induced toxicity. It was shown that HaCaT cell line provides a useful model to study components with toxicity or antioxidant activity. Our results indicated that (i) glyphosate-based formulations can be responsible for oxidative damage to human epidermal cells, (ii) antioxidant compounds should be associated to herbicide formulations to decrease their deleterious effects on human skin. The use of an experimental design connected with the simplex method can be consider to be a fast technique to classify, with a limited number of experiments, the respective role of five parameters in the in vitro cytoprotection by antioxidants of herbicide-induced toxicity.

Concentration of sodium ion as the determining factor for the association of dansyl amino acids with the teicoplanin molecule in reversed-phase liquid chromatography.

The mechanism of the binding of D,L dansyl amino acids to teicoplanin was investigated. Na+ was used as an indicator of the interactions between the solutes and teicoplanin. The number (n) of sodium ions, Na+, excluded from the solute-teicoplanin interface when analyte transfer occurred was determined. A thermodynamic study and enthalpy-entropy compensation were performed to further explore the interaction mechanism. From these results, it was shown that teicoplanin was balanced between 2 conformational states characterized by distinct enantioselective properties. This approach indicates that liquid chromatography (LC) is a useful tool to extract physicochemical and molecular information from retention data. Thus, LC can be used as a complementary technique with the conventional techniques of molecular interaction analysis.

Triazine-human serum albumin association: thermodynamic approach and sodium effect.

Human serum albumin (HSA) serves as a carrier protein to transport triazine herbicides to molecular targets. In this paper, a theoretical treatment was developed to describe the HSA-triazine herbicides association. A determination of the association constant, K, as well as the degree of complexation n(c) (the percent of complex guest) was carried out. Enthalpy-entropy compensation was also analyzed in relation to this mathematical model to confirm the herbicide complexation behavior with HSA. The role of the sodium cation (Na(+)) on this association was investigated. It was expected that the sodium ion would act on the herbicide-HSA association process by modifying the surface tension of the bulk solvent and increase the K and n(c) values. The results showed that for patients who suffer from Na(+) desequilibrium, the triazine-HSA binding would change and as well the toxicological effect of these herbicides.

Role of the Na+ ion on phenol derivatives/hydroxypropyl-beta-cyclodextrin complex formation on porous graphitic carbon phase.

The reversed-phase liquid chromatography retention of phenol derivatives was investigated over a concentration range of sodium chloride (0-10(-2) M) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) (0-35x10(-3) M) using a porous graphitic carbon (PGC) stationary phase and a methanol/water mixture (50:50 (v/v)) as the mobile phase. A theoretical treatment was developed to investigate the effect of the sodium chloride and hydroxypropyl-beta-cyclodextrin on the equilibrium between the solutes with the PGC surface and the aqueous medium, respectively. The thermodynamic parameter variations were calculated using van't Hoff plots. It was expected that the sodium ion acted on the solute-PGC association process by modifying the surface tension of both the bulk solvent and the PGC surface. The phenol derivative/HP-beta-cyclodextrin complexation was shown to be entropically controlled for all the solutes except for the one which contained the -NO2 group in its structure, i.e. the nitro phenol derivative. A comparison of the compensation temperature of the solute-PGC association process when sodium chloride and HP-beta-CD concentration changed in the mobile phase led to the conclusion that these two modifiers acted via a variation in the hydrophobic effect.

Supercoiled circular DNA and protein retention in non-equilibrium chromatography temperature and velocity dependence: testimony of a transition.

Non-equilibrium chromatography (NEC) is a chromatographic mode for the rapid separation of polymers. The retention behavior of various proteins (human, chicken, bovine serum albumin) and supercoiled circular double-stranded DNA (plasmids) was investigated using a phosphate buffer as a mobile phase at different velocities and column temperatures with a C1 column with very low-packing particle diameter as a stationary phase. It was shown that the two factors (temperature and velocity) constituted important parameters in the retention mechanism of plasmids and proteins in NEC. The protein was retained more than the plasmid. At all the temperatures (5, 10, 15, 20, 25 degrees C) the plasmid retention increased over the entire flow-rate range (0.02-1.8 ml/min). For the protein, the retention curve presented a decrease in the relative retention time until a critical value of the mobile phase flow-rate, followed by an increase. The transition between the two well known NEC methods, slalom chromatography and hydrodynamic chromatography was clearly visualized for proteins at the lowest temperature, but did not appear for plasmids due to their strong compact structure.

Separation in slalom chromatography: stretching and velocity dependence.

Slalom chromatography (SC) is used for the separation of large double-stranded DNA molecules. In this technique, the progression of the DNA fragments through the closed column packing follows the flow direction and is like a snake edging is way into long grass. A novel mathematical model is developed in this paper to describe this hydrodynamic phenomenon. The results obtained provided a model for the resolution between two adjacent peaks on a chromatogram. As well, a chromatographic response function was used to obtain the most efficient separation conditions for a mixture of DNA fragments with sizes higher than 15 kbp in a minimum analysis time.

Chiral discrimination of phenoxypropionic acid herbicide enantiomers on teicoplanin phase: methanol dependence and eluent pH consideration.

The chiral recognition mechanism for a series of d,l phenoxypropionic acid herbicides (PPAs) on a teicoplanin stationary phase was investigated in reversed phase liquid chromatography (RPLC) over a wide range of mobile phase pH and column temperature. The effect of methanol on the enantiomeric separation was studied by varying its fraction (v/v) in the mobile phase. The thermodynamic data indicated that the chiral recognition was controlled by the interaction between the anionic form of the solute and the teicoplanin phase while those with the neutral form played a minor role. In addition, it was demonstrated that the enhancement of the separation factor observed as the methanol fraction increased in the mobile phase was enthalpically controlled owing to stereoselective binding interactions. Such behavior was used to optimize the chromatographic conditions for separation of PPAs herbicides on teicoplanin.