These data indicate a significant role for macrophages in causing acute rejection-related tissue injury that is, at least in part, targeted to the microcirculation.

The present results identify contrasting changes in the microanatomy of vascular and lymphatic beds in endstage renal allografts associated with subpopulations of infiltrating macrophages and B cells that potentially regulate some of these changes. These cells and processes could become a new therapeutic target in chronic allograft failure.

The α2,3‐sialylation of N‐glycans is considered important but complicated because the functions of the three β‐galactoside α2,3‐sialyltransferases, ST3GAL3, ST3GAL4, and ST3GAL6, could be compensating for one another. To distinguish their specific functions, we established each individual knockout (KO) cell line. Loss of either the ST3GAL3 or ST3GAL6 genes decreased cell proliferation and colony formation, as opposed to the effect in the ST3GAL4 KO cells. The phosphorylation levels of ERK and AKT were significantly suppressed in the ST3GAL6 KO and ST3GAL3 KO cells, respectively. The cell aggregations were clearly observed in the KO cells, particularly the ST3GAL3 KO and ST3GAL6 KO cells, and the expression levels of E‐cadherin and claudin‐1 were enhanced in both those cell lines, but were suppressed in the ST3GAL4 KO cells. Those alterations were reversed with an overexpression of each corresponding gene in rescued cells. Of particular interest, the α2,3‐sialylation levels of β1 integrin were clearly suppressed in the ST3GAL4 KO cells, but these were increased in the ST3GAL3 KO and ST3GAL6 KO cells, whereas the α2,3‐sialylation levels of EGFR were significantly decreased in the ST3GAL6 KO cells. The decrease in α2,3‐sialylation increased the α2,6‐sialylation on β1, but not EGFR. Furthermore, a cross‐restoration of each of the three genes in ST3GAL6 KO cells showed that overexpression of ST3GAL6 sufficiently rescued the total α2,3‐sialylation levels, cell morphology, and α2,3‐sialylation of EGFR, whereas the α2,3‐sialylation levels of β1 were greatly enhanced by an overexpression of ST3GAL4. These results clearly demonstrate that the three α2,3‐sialyltransferases modify characteristic target proteins and regulate cell biological functions in different ways.

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Since hypobaric hypoxia significantly affects metabolic characteristics of intestinal flora, which plays an important role in the biotransformation of aspirin, high altitudes may influence the pharmacokinetics and therapeutic effects of aspirin in the intestines. In the present study, to test alterations of intestinal microbiota at high altitude comparing to that at low altitude, we analyzed rat feces from plain group and high-altitude group by 16S rRNA analysis. To detect concentrations of aspirin and salicylic acid, we established a reliable liquid chromatography tandem mass spectrometry method to measure aspirin and salicylic acid concentrations in fecal suspensions and plasma. Our study found that the plateau hypoxic environment caused a significant increase in Bacteroides in rat feces, while Corynebacterium, Prevotella, and Coprococcus were declined. In addition, compared with the plain group, the metabolic activity of fecal suspensions from the plateau group on aspirin was significantly reduced. More importantly, these changes in the intestinal microbiota led to increasing absorption of aspirin in the rats after rapidly ascent to the plateau, and a reduction in the pharmacodynamic index TXB2, which would possibly result in bleeding. In conclusion, our research provides new ideas for changes in plateau pharmacokinetics, and then guide the corresponding reduction in aspirin dose for the population quickly entering the plateau.

Investigation of the cultured mycelia of Cordyceps ophioglossoides resulted in the isolation and characterization of three new unusual spiro[4.5]decane sesquiterpenes, cordycepol A (1), cordycepol B (2), and cordycepol C (3), and a new fumagillol analogue, cordycol (4). Their structures were established by spectroscopic means. The cytotoxic activities were also evaluated, compounds 3 and 4 showing their IC50 values in the range of 12–33 μg/ml against HeLa and HepG2 (Table 3). In addition, 3 and 4 were not obviously harmful towards normal liver cell lines LO2, showing IC50 values above 80 μg/ml.