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Membrane-modification effects, induced by ultraviolet (UV) irradiation in diacetylenic liposomes, were analyzed upon contact with cells, biological membranes, and proteins. Liposomes formulated with mixtures of unsaturated 1,2-bis(10,12-tricosadiynoyl)- sn-glycero-3-phosphocholine and saturated 1,2-dimyristoyl- sn-glycero-3-phosphocholine, in a 1:1 molar ratio, were compared with those that were UV-irradiated and analyzed in several aspects. Membrane polymerization inherence on size stability was studied as well as its impact on mitochondrial and microsomal membrane peroxidation induction, hemolytic activity, and cell viability. Moreover, in order to gain insight about the possible irradiation effect on interfacial membrane properties, interaction with bovine serum albumin (BSA), lysozyme (Lyso), and apolipoprotein (apoA-I) was studied. Improved size stability was found for polymerized liposomes after a period of 30 days at 4°°C. In addition, membrane irradiation had no marked effect on cell viability, hemolysis, or induction of microsomal and mitochondrial membrane peroxidation. Interfacial membrane characteristics were found to be altered after polymerization, since a differential protein binding for polymerized or nonpolymerized membranes was observed for BSA and Lyso, but not for apoA-I. The substantial contribution of this work is the finding that even when maintaining the same lipid composition, changes induced by UV irradiation are sufficient to increase size stability and establish differences in protein binding, in particular, reducing the amount of bound Lyso and BSA, without increasing formulation cytotoxicity. This work aimed at showing that the usage of diacetylenic lipids and UV modification of membrane interfacial properties should be strategies to be taken into consideration when designing new delivery systems. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) is a low-grade lymphoid malignancy incurable with conventional modalities of chemotherapy. Strong and constitutive nuclear factor kappa B (NF-kappaB) activation is a characteristic of CLL cells. We examined the effects of a new NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on CLL cells. Dehydroxymethylepoxyquinomicin completely abrogated constitutive NF-kappaB activity and induced apoptosis of CLL cells. Apoptosis induced by DHMEQ was accompanied by downregulation of NF-kappaB-dependent antiapoptotic genes: c-IAP, Bfl-1, Bcl-X(L) and c-FLIP. Dehydroxymethylepoxyquinomicin also inhibited NF-kappaB induced by CD40 and enhanced fludarabine-mediated apoptosis of CLL cells. Results of this study suggest that inhibition of constitutive and inducible NF-kappaB by DHMEQ in combination with fludarabine is a promising strategy for the treatment of CLL. [ABSTRACT FROM AUTHOR]

Contralateral dominance in the activation of the primary sensorimotor cortex (S1/M1) during tongue movements (TMs) has been shown to be associated with a chewing-side preference (CSP). However, little is known about its interaction with chewing-related cortical activation. Functional magnetic resonance imaging was performed before and after gum-chewing in six subjects who exhibited a left CSP to determine the relationship between the CSP and activation patterns in the S1/M1 during TMs. Before the subjects chewed the gum, activation foci were found in the bilateral S1/M1. In the left hemisphere, both signal intensity and the area of activation significantly increased during TMs within 10 min after subjects chewed gum. Moreover, this augmented activation significantly decreased within 20 min during tongue protrusion and leftward movement. In the right hemisphere, there were no marked changes during TMs. These results suggest that bilateral gum-chewing enhances activation of the S1/M1 ipsilateral to the CSP during TMs. [ABSTRACT FROM AUTHOR]

Abstract Background In recent years, increasing attention has been paid to the effects of low-dose irradiation on human health. We examined whether low-dose irradiation affected the functions of mesenchymal stromal/stem cells (MSCs), which are tissue/organ-supportive stem cells, derived from bone marrow (BM). Methods Normal human BM-MSCs from five healthy individuals were used in this study. Culture-expanded BM-MSCs were exposed to 0.1 gray (Gy) of γ-radiation (Cesium-137) at a rate of 0.8 Gy/min (Ir-MSCs), and their expansion, multi-differentiation, and hematopoiesis-supportive capabilities were investigated. Results The expansion of BM-MSCs was transiently delayed after low-dose γ-irradiation compared with that of non-irradiated BM-MSCs (non-Ir-MSCs) in two out of five lots. Adipogenic and osteogenic differentiation capabilities were not significantly affected by low-dose irradiation, although one lot of BM-MSCs tended to have transiently reduced differentiation. When human BM hematopoietic stem/progenitor cells (HPCs) were co-cultured with Ir-MSCs, the generation of CD34+CD38+ cells from HPCs was enhanced compared with that in co-cultures with non-Ir-MSCs in two out of five lots. The mRNA expression level of interleukin (IL)-6 was increased and those of stem cell factor (SCF) and fms-related tyrosine kinase 3 ligand (Flt3L) were decreased in the affected lots of Ir-MSCs. In the other three lots of BM-MSCs, a cell growth delay, enhanced generation of CD34+CD38+ cells from HPCs in co-culture, and a combination of increased expression of IL-6 and decreased expression of SCF and Flt3L were not observed. Of note, the characteristics of these affected Ir-MSCs recovered to a similar level as those of non-Ir-MSCs following culture for 3 weeks. Conclusions Our results suggest that acute exposure to low-dose (0.1 Gy) radiation can transiently affect the functional characteristics of human BM-MSCs.

Abstract The therapeutic effects of mesenchymal stromal/stem cells (MSCs) are mainly based on three characteristics: immunomodulation, tissue regeneration, and hematopoietic support. Cell therapy using culture-expanded MSCs is effective in some intractable bone and hemato-immune disorders; however, its efficacy is limited. In this article, we review the previous efforts to improve the clinical outcomes of cell therapy using MSCs for such disorders. We describe pharmacological targeting of endogenous bone marrow-derived MSCs as a crucial quality-based intervention to establish more effective MSC-based therapies.

Background: Enzymes responsible for cell wall development in Mycobacterium tuberculosis are considered as potential targets of anti-tuberculosis (TB) agents. Mycobacterial cyclopropane mycolic acid synthase 1 (CmaA1) is essential for mycobacterial survival because of its critical role in synthesizing mycolic acids. Materials and Methods: We screened compounds that were capable of interacting with the mycobacterial CmaA1 active site using a virtual compound library with an in silico structure-based drug screening (SBDS). Following the selection of such compounds, their antimycobacterial activity was examined. Results: With the in silico SBDS, for which we also used DOCK-GOLD programs and screening methods that utilized the structural similarity between the selected active compounds, we identified two compounds with potent inhibitory effects on mycobacterial growth. The antimycobacterial effect of the compounds was comparable to that of isoniazid, which is used as a first-line anti-TB drug. Conclusion: The compounds identified through SBDS were expected to be a novel class of anti-TB pharmacophores.

summary The purpose of this investigation was to examine by reverse-transcriptase polymerase chain reaction analysis the osteogenic differentiation of twice-passaged Sprague–Dawley rat bone marrow stromal cells in type I collagen gel cultured for 3 weeks. Two culture media were used here, namely Dulbecco's modified Eagle (DME) medium supplemented with vitamin C [Dex (–)] and those with vitamin C, dexamethasone and β -glycerophosphate [Dex (+)]. Culture with Dex (–) medium in collagen gel for 3 weeks brought about the well-developed cell network and middle-stage osteogenic phenotype expression characterized by mRNA for alkaline phosphatase, osteonectin and osteopontin while those for bone sialo protein and osteocalcin were not detected. On the contrary, culture with Dex (+) medium in collagen gel for 3 weeks lead to necrosis of the cells. These results indicate that culture in collagen gel with Dex (–) DME medium containing vitamin C was useful for three-dimensional culture and middle-stage osteogenic differentiation of twice-passaged bone marrow stromal cells. This study might contribute to tissue engineering therapy to fix bone and periodontal defects in the future. [ABSTRACT FROM AUTHOR]

summary The purpose of this investigation was to examine the effects of the addition of five cytokines such as vitamin C, vitamin D, bone morphogenetic protein (BMP), transforming growth factor-β (TGF-β ) and dexamethasone (Dex) to Dulbecco's modified Eagle (DME) medium on the proliferation of Sprague–Dawley (SD) rats' bone marrow stromal cells and osteoblastic MC3T3-E1 cells by conducting 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. For bone marrow stromal cells, vitamin C was needed for doubling the cell viability. While BMP, TGF-β and vitamin D maintained the growth rate given by vitamin C, Dex with β -glycerophosphate (β -GP) slightly reduced this cell proliferation rate. For MC3T3-E1 cells, the addition of four cytokines examined (vitamin C, vitamin D, TGF-β and BMP) did not significantly increase the cell proliferation while Dex with vitamin C and β -GP slightly enlarged the cell proliferation. It can be pointed out that vitamin C in DME medium is indispensable for rapid proliferation of bone marrow stromal cells that contain many osteo-progenitor cells but is not effective for quick increase of osteoblastic MC3T3-E1 cells. This finding appears to contribute to tissue engineering therapy to fix bone and periodontal defects in dentistry. [ABSTRACT FROM AUTHOR]

summary Polylactide copolymer and collagen are now used as bio-absorbable scaffold materials for restoration of lost oral tissues. Polylactide caprolactone (PLCL) sponge and collagen gel were examined for their cellular reactions when implanted in 8-week-old Sprague–Dawley (SD) rats’ subcutaneous tissues for up to 8 weeks. The PLCL sponges were slowly absorbed by a mild chronic inflammation process in which multinucleated giant cells covered and slowly captivated the sponge surfaces without thick encapsulation. On the other hand, collagen gel was surrounded by thick inflammatory reaction zones and infiltrated by acute inflammation cells including neutrophils, lymphocytes and macrophages, and disappeared more rapidly. Although the bio-absorption process differed, both materials, when combined, appear to be useful scaffold materials for tissue engineering therapy in future dental practice. [ABSTRACT FROM AUTHOR]