Loss of B7-H1 expression by recipient parenchymal cells leads to expansion of infiltrating donor CD8+ T cells and persistence of graft-versus-host disease

Previous experimental studies have shown that acute graft-versus-host disease (GVHD) is associated with two waves of donor CD8(+) T cell expansion. In the current studies, we used in vivo bioluminescent imaging, in vivo BrdU labeling, and three different experimental GVHD systems to show that B7-H1 expression by recipient parenchymal cells controls the second wave of alloreactive donor CD8(+) T cell expansion and the associated second phase of GVHD. Loss of B7-H1 expression by parenchymal cells during the course of GVHD was associated with persistent proliferation of donor CD8(+) T cells in GVHD target tissues and continued tissue injury, whereas persistent expression of B7-H1 expression by parenchymal cells led to reduced proliferation of donor CD8(+) T cells in GVHD target tissues and resolution of GVHD. These studies demonstrate that parenchymal cell expression of B7-H1 is required for tolerizing infiltrating T cells and preventing the persistence of GVHD. Our results suggest that therapies designed to preserve or restore expression of B7-H1 expression by parenchymal tissues in the recipient could prevent or ameliorate GVHD in humans.     

The Novel Pro-Osteogenic Activity of NUCB21–83

NUCB2^1–83 has been recently reported as an anorexigenic and anti-hyperglycemic peptide. Here we report that NUCB2^1–83 promotes osteogenesis. It was found after two months of once-a-day intravenous injection of NUCB2^1–83, bone mineral density of femora and lumbar vertebrae were increased in ovariectomized rats. NUCB2^1–83 also increased the alkaline phosphatase activity and promoted mineralization in mouse MC3T3-E1 preosteoblastic cell line. When either both Arg⁶⁰ and Arg⁶³ or Ser⁷² were mutated to Ala, the pro-osteogenic activity was completely lost, indicating that these residues are structurally important for its biological function. Furthermore, it encumbered osteoclastic differentiation of RAW 264.7 macrophage. It also excluded any possibility of the effect caused by contaminants or experimental faults, and demonstrated that the pro-osteogenic activity observed was a specific effect of NUCB2^1–83 itself. These findings warranted that further studies on NUCB2^1–83 would be valuable for the treatment of bone metabolic diseases especially for osteoporosis.     

苏铁白化苗叶片细胞的超微结构

本文系苏铁白化苗研究系列报道之二。应用超薄切片和电镜观察技术对苏铁白化苗叶片细胞的超微结构观察,结果表明,苏铁白化苗叶片细胞的超微结构与绿苗的相比有明显不同,前者的细胞质含量稀少,未见有结构完整的叶绿体和线粒体,但见有呈支解、游离状的类似叶绿体片层的膜结构和内嵴几乎完全消失的退化线粒体存在;后者的细胞结构正常。     

Effect of P-glycoprotein Inhibition on the Penetration of Ceftriaxone Across the Blood–Brain Barrier

Neurochemical Research - Recent studies indicate that inhibition of the efflux transporter P-glycoprotein (P-gp) at the blood–brain barrier (BBB) may represent a putative strategy to increase...