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To achieve a tumor-targeted drug delivery system for photodynamic therapy, we designed ligand-mediated nanoparticles with stable formulations of a hydrophobic photosensitizer. Folic acid (FA)-conjugated amphiphilic block copolymers of PEG and poly-β-benzyl-L-aspartate with the potential to act as pH-sensitive drug release reservoirs were synthesized. The photosensitizer was conjugated to the copolymers through pH-sensitive hydrazone (Hyd) linkages. The FA-PEG-P(Asp-Hyd)-Pheo nanoparticles had average diameters of 76–217 nm. The pH-dependent photosensitizer release property may ensure intracellular drug release inside tumor cells due to the lower pH inside the endosomes and lysosomes of tumor cells. The FA-PEG-P(Asp-Hyd)-Pheo nanoparticles demonstrated marked phototoxicity and minimal dark toxicity. [ABSTRACT FROM PUBLISHER]

Circadian preference has been considered related with impulsivity. The purpose of the present study was to evaluate the relationship between circadian typology and impulsivity measured by the Barratt Impulsivity Scale (BIS), sensation-seeking measured by the Sensation Seeking Scale - Form V (SSS-V) and response inhibition elicited by the GO/NO-GO paradigm. A total of 503 Korean healthy college students (288 males and 215 females) completed the Composite Scale of Morningness (CSM) for circadian typology and the BIS and SSS-V for impulsivity and risk taking, respectively. A subset of 142 subjects additionally performed the computerized GO/NO-GO task for motor response inhibition. A significant association was found between the circadian typology of the CSM and impulsivity of the BIS and disinhibition of SSS-V. In addition, there was a difference in trend level between the circadian typology and response inhibition elicited by the GO/NO-GO test. Regarding circadian preference, evening types were significantly associated with higher impulsivity on the BIS, disinhibition on the SSS-V and lower rate of successful inhibition on the GO/NO-GO task compared to morning types. The present results showed significant relationships between circadian preference and impulsivity and sensation-seeking personality traits. In particular, our findings suggest that high impulsivity, disinhibition and impaired response inhibition are more related to evening types. Circadian preference might be associated with psychiatric problems interacting with some aspects of personality traits such as inhibitory control. [ABSTRACT FROM AUTHOR]

Iris loczyi is a perennial rhizomatous herb distributed in Central Asia. We examined genomic architecture of the complete chloroplast genome in I. loczyi by assembling the Illumina MiSeq reads using de novo strategy. The chloroplast genome is 150,940 bp in length harboring 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. It exhibits typical quadripartite structure comprising LSC (80,907 bp), SSC (17,853 bp), and a pair of IRs (26,090 bp). Phylogenetic analysis of 20 chloroplast genomes from Asparagales revealed that Iridaceae is a monophyletic group and the I. loczyi is clustered together with the congener, I. sanguinea. [ABSTRACT FROM AUTHOR]

It has been reported that myocardial glutathione content is decreased during ischemia-reperfusion, but the mechanism of glutathione depletion has remained unclear. The present study tested whether osmotic stress is involved in the glutathione depletion during ischemia. Six hours of hypoxic acidosis with either high CO2 tension or low HCO3−− concentration, which simulates the ischemic condition, resulted in a significant decrease of glutathione content and the glutathione depletion was prevented by hyperosmolarity. High-CO2 acidosis alone without hypoxia induced a similar degree of glutathione depletion. Intracellular pH was lowered by high-CO2 acidosis to 6.41 ±± 0.03 in 15 min. Meanwhile, the cell size gradually increased and reached ∼∼110% in 10 min and the increased cell size was maintained for at least 30 min, which was also prevented by hyperosmolarity. Subsequent experiments observed the effects of simulated reperfusion on the glutathione content. Measured in 1 h after the hypoxic acidotic reperfusion, the glutathione content was further decreased compared to the level at the end of ischemia, which was not suppressed by increasing the osmolarity of reperfusion solution. The degree of glutathione depletion during hypoxic reperfusion with normal pH was similar to the hypoxic acidotic reperfusion group. On the other hand, normoxic reperfusion was not accompanied by further depletion of glutathione content. Based on these results, it was concluded that ischemia induces the glutathione depletion via osmotic stress, which results from intracellular acidification, and the glutathione content is further decreased during reperfusion through a mechanism other than oxygen toxicity. [ABSTRACT FROM AUTHOR]

In addition to heme-irons, reactive (β-globin thiols (βCys93s) of hemoglobin (Hb) also have been shown to interact with endogenous nitric oxide (NO) thereby contributing to vascular tone regulation. What relative roles do these NO binding sites contribute to the overall Hb-mediated vasoactivity? Several test Hbs with either or both the NO binding sites preliganded or blocked were prepared and tested in a rat thoracic aortic ring model. Hbs tested were: NEM-Hb (ferrous Hb with masked thiols), HbNO (ferrous Hb preliganded with NO), Hb+CN (ferric Hb liganded with CN−), NEM-HbNO and NEM-Hb+CN (Hbs with both heme-iron and cysteine sites preliganded or blocked). Typically, >0.2 μM control Hb significantly increased isometric tension in agonist stimulated vessel rings (58.1 ±7.0% over baseline). At comparable concentrations, NEM-Hb also caused a significant contraction (50.7±9.5%) while HbNO and Hb+CN did not (−5.5±6.0% and −3.7±4.6%, respectively). For these Hbs, masking thiols as well did not significantly alter respective vascular effects. Ferrous sperm whale myoglobin (Mb), which has no reactive thiol, elicited a significant contraction (55.1±13.2%) while metMb did not (−0.8±3.2%), suggesting the relative importance of heme-iron ligand and oxidation state in Hb vasoactivity. Additionally, ferrous or ferric equine heart cytochrome-C, a heme protein with no readily available heme-iron and cysteine binding sites, did not elicit notable contraction. Human Hb variants in which (βCys93s are deleted or substituted with non-cysteine residues did not reveal any documented significant hemodynamic abnormalities. These results indicate that reactive globin-thiols do not appear to play a prominent role relative to heme-irons in Hb-mediated vasoconstriction. [ABSTRACT FROM AUTHOR]

It has been observed that H9c2 cardiac cells cultured in physiologic solutions exhibit delayed cell death after repeated medium replacements, of which the cause was the relatively mild osmotic challenges during the renewal of the culture medium. Interestingly, the cell damage was associated with altered intracellular GSH homeostasis. Therefore, this study attempted to elucidate the effects of osmotic stress on GSH metabolism. In cells subjected to osmotic stress by lowering the NaCl concentration of the medium, the cell swelling was rapidly counterbalanced, but the intracellular GSH content was significantly lower in 3 h. Meanwhile, the ratio of GSH-to-GSSG was not affected. As expected, osmotic stress also increased the sensitivity to H2O2, which was attributable to the decrease of GSH content. The decrease of GSH content was similarly evident when the synthetic pathways of GSH were blocked by BSO or acivicin. It was concluded that osmotic stress induced the decrease of intracellular GSH content by increased consumption and this loss of GSH rendered the cells susceptible to a subsequent oxidative stress. [ABSTRACT FROM AUTHOR]

In this brief overview, recent progress and current status of blood substitute research and development is summarized. Current blood substitute development efforts are focused on red blood cell substitutes but substitutes for platelets and other blood components are also in progress. Red cell substitutes currently in various stages of development are semi-synthetic or synthetic oxygen carriers that include “stealth” or “masked” red cells, hemoglobin-based oxygen carriers and perfluorocarbon-based oxygen carriers. Artificial platelets (or platelet substitutes) are in early stages of development and include human platelet fragments or particles of synthetic/semi-synthetic materials or recombinant human serum albumin coupled with platelet surface receptor fragments. Of note, some recombinant clotting factors (Factors VII, VIII, IX) have already been successfully developed and licensed for treatment of hemophilia. In addition, some future approaches and prospects of blood component replacement therapeutics are discussed. [ABSTRACT FROM AUTHOR]

A correction to the article "Toward 21st century blood component replacement therapeutics: Artificial oxygen carriers, platelet substitutes, recombinant clotting factors, and others," published in the previous issue of the periodical.