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YM-2A directly enhances proliferation from macrophages and DCs.
Colon-26 tumor cells (A), spleen cells (B), peritoneal macrophages (C and D), and bone marrow DCs (E and F) were incubated with YM-2A or indicated compounds for 24 h. (C and E) After incubation, cell proliferation was measured using WST-8 assay. (D and F) For BrdU Assay, cells were incubated with YM-2A in presence of BrdU (10 μM). Representative plots (right) and summarized data (left) were shown as the percentage of cells incorporating BrdU. The data presented are representative of two independent experiments. *p p p < 0.001, compared with control or 0 μg/ml of YM-2A.</p
YM-2A is resistant to digestive enzymes and orally administered YM-2A activates antigen-presenting cells in GALTs.
(A) After treatment with pancreatic α-amylase, glycogens were analyzed using HPLC. #Negative solvent peak (11.84 min). (B) On day 14 after colon-26 inoculation in BALB/c mice, Peyer’s patch cells were stained with specific antibodies. Histograms showing expression level of MHC class II and CD86 were measured by flow cytometry. (C) Mean fluorescence intensity (MFI) expressed by macrophages (F4/80+) or DCs (CD11c+) was analyzed. (D) Whole Peyer’s patch cells and CD11c+ MACS column-enriched Peyer’s patch CD11c+ cells were stained with anti-MHC class II and CD11c. (E) MACS-enriched Peyer’s patch CD11c+ cells were incubated with YM-2A (100 μg/ml) or LPS (1 μg/ml) for 24 h. After incubation, mRNA expression levels of cytokines were determined by real-time PCR. The relative expression level was normalized to the expression level with the control. *p p p < 0.001, compared with the control.</p
YM-2A increases various cytokine production from macrophages and DCs.
Peritoneal macrophages (A-C), and bone marrow DCs (D-F) were incubated with YM-2A for 24 h. After incubation, TNF-α or IL-12 levels in the collected supernatants were measured by ELISA (A, B, D and E) and mRNA expression levels of cytokines were determined by real-time PCR (C and F). The relative expression level was normalized to the expression level with 0 μg/ml control. (G) Morphological change in macrophage. Morphology of macrophage visualized by optical microscopy (×400) (G, left panels). The activation index percentage was expressed as the number of cells with activated morphology relative to the total number of cells, quantified in 3–4 random fields (number of total cells >100) (G, right panels). The data presented are representative of two independent experiments. *p p p < 0.001, compared with 0 μg/ml control.</p
YM-2A provides therapeutic benefit in colon-26 tumor-bearing mice.
(A) Experimental scheme. YM-2A (2.5 mg or 5 mg/mouse) was orally administered (daily, 5 days/week) from day 0 (pre-treatment) or day 8 (post-treatment). (B and C, left) Tumor volume (n = 5 for colon26 model, n = 6~7 for B16 model) represents the means ± S.E. of two separate experiments. **p p p p 3. Survival rates are represented using Kaplan–Meier curves.</p
YM profiles across CXL and control corneas.
<p>A) Corneas dissected in PBS. B) Corneas dissected without any fluid (“DRY”). An increasing YM toward the corneal surface (<i>d</i> = 0) was found in the CXL samples. An exponential function (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088186#pone.0088186.e002" target="_blank">Equation 2</a>) was fit to the YM profiles of CXL samples, giving <i>E</i><sub>max</sub> (YM at the corneal surface) and <i>E</i><sub>0</sub> (YM at the endothelial side). The CXL zone of effective cross-linking was defined as the zone where the YM of the fit exceeded 1.4 <i>E</i><sub>0</sub>. Error bars: geometric standard error interval.</p
Sakurajima-Satsuma (Sz-S) and Noike-Yumugi (N-Ym) tephras: new tephrochronological marker beds for the last deglaciation, southern Kyushu, Japan
Two prominent tephras, Sakurajima-Satsuma (Sz-S) erupted from Sakurajima volcano and Noike-Yumugi (N-Ym) erupted from Kuchierabujima Island, provide new key marker beds for dating and synchronizing palaeoenvironmental and archaeological records in the last deglaciation in southern Japan. These tephras were identified on the basis of glass major-element compositions in two distal areas, a marine core (IMAGES MD98-2195) in the northern part of the East China Sea and on the central part of Tanegashima Island, and related their stratigraphic positions to the marine oxygen isotope-based chronology. In MD98-2195, Sz-S, 0.8 cm in thickness at 9.12 m depth and N-Ym, 3 cm in thickness at 9.30 m depth, are both white, vitric, ash-grade tephras. On Tanegashima Island, Sz-S, 10 cm in thickness and N-Ym, 3 cm in thickness, are stratigraphically constrained by well-characterised marker tephras Kikai-Akahoya (7,300 cal BP) and Aira-Tn (29,000 cal BP). Sz-S is rhyolitic and homogeneous on the basis of glass major-element compositions assayed by electron microprobe. Pumiceous glass shards predominant in distal Sz-S tephra indicate that it derived from pumice fall units that correspond to pumiceous and phreatomagmatic fine ash units constituting proximal Sz-S tephra. N-Ym is rhyolitic and glass major-element analyses reveal compositional diversity between units, suggesting that the lower and middle tephra units dispersed to the east, whereas the upper unit was dispersed north to north-west from the vent.
Stratigraphically, Sz-S occurs at around the start of the late-glacial reversal (cooling) in oxygen isotope records of MD98-2195, corresponding to the end of GI-1 and the start of GS-1 in the ice-core events of NGRIP (GICC05), consistent with a terrestrial age of ˜12,800 cal BP. Based on the oxygen isotope stratigraphy, the tephra identified in the core as N-Ym at 9.30 m depth is close to the end of Greenland GI-1 and hence has an age of ˜13,000 cal BP, but on Kuchierabujima Island it has an age based on ¹⁴C assay of charcoal of c. 14,900 cal BP. Although this age discrepancy (14.9 vs 13.0 cal ka) needs resolution, the occurrence in core MD98-2195 of N-Ym shows that it is more widespread than hitherto demonstrated. The widespread distributions and key stratigraphic positions for the two marker tephras indicate that they are thus critical isochrons for precise correlation of palaeoenvironmental changes and prehistoric cultural events during the last deglaciation in southern Kyushu, and for relating such changes and events to the ice-core chronology via the marine oxygen isotope chronostratigraphy
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