Objective.To investigate the pathological significance of tubuloreticular structure(TRS) and cylindri- cal confronting cisternae(CCC) in patients with lupus nephritis. Methods. An electron microscopical study of 24 re...Objective.To investigate the pathological significance of tubuloreticular structure(TRS) and cylindri- cal confronting cisternae(CCC) in patients with lupus nephritis. Methods. An electron microscopical study of 24 renal biopsy specimens from patients with lupus nephritis was carried out, with particular emphasis on two endoplasmic reticulum(ER)-related structures. Result. TRS was found in 18 cases, and CCC in 10 of them. TRS often appeared in the capillary en- dothelium,and did not correlate well with the activity index of lupus nephritis. CCC appeared frequently in monocyte/macrophage and lymphocyte, and correlated well with both the activity index and the amount of interstitial immune deposits. Conclusion.TRS and CCC derived from inward "budding" of ER membrane were suggested and the morphogenesis and morphologic variations of CCC were discussed. Both TRS and CCC are pathognomonic, though not specific changes. They may be helpful in pathologic diagnosis of lupus nephritis, when properly combined with certain clinical and pathological features.展开更多
Polo-like kinase 1 （Plkl）, a member of a family of serine/threonine kinases, is an attractive target for the development of anti- cancer drugs because it is involved in the regulation of cell-cycle progression and c...Polo-like kinase 1 （Plkl）, a member of a family of serine/threonine kinases, is an attractive target for the development of anti- cancer drugs because it is involved in the regulation of cell-cycle progression and cytokinesis. This kinase provides two pock- ets for developing Plkl inhibitors： the N-terminal catalytic domain （NCD） and the polo-box domain （PBD）. For both of the two pockets, some natural products were identified as Plkl inhibitors and some synthetic Plkl inhibitors were developed by mimicking ATP and phosphopeptides, natural products binding to NCD and PBD respectively. This article not only reviews the progression of Plkl inhibitors binding to these two pockets, but also discusses diversity evolution and jump in the process of drug development using Plkl inhibitors as examples and how they impact on drug design and pharmacopbore modeling.展开更多
文摘Objective.To investigate the pathological significance of tubuloreticular structure(TRS) and cylindri- cal confronting cisternae(CCC) in patients with lupus nephritis. Methods. An electron microscopical study of 24 renal biopsy specimens from patients with lupus nephritis was carried out, with particular emphasis on two endoplasmic reticulum(ER)-related structures. Result. TRS was found in 18 cases, and CCC in 10 of them. TRS often appeared in the capillary en- dothelium,and did not correlate well with the activity index of lupus nephritis. CCC appeared frequently in monocyte/macrophage and lymphocyte, and correlated well with both the activity index and the amount of interstitial immune deposits. Conclusion.TRS and CCC derived from inward "budding" of ER membrane were suggested and the morphogenesis and morphologic variations of CCC were discussed. Both TRS and CCC are pathognomonic, though not specific changes. They may be helpful in pathologic diagnosis of lupus nephritis, when properly combined with certain clinical and pathological features.
基金supported by the Fundamental Research Funds for the Central Universities(2013HGCH0015)
文摘Polo-like kinase 1 （Plkl）, a member of a family of serine/threonine kinases, is an attractive target for the development of anti- cancer drugs because it is involved in the regulation of cell-cycle progression and cytokinesis. This kinase provides two pock- ets for developing Plkl inhibitors： the N-terminal catalytic domain （NCD） and the polo-box domain （PBD）. For both of the two pockets, some natural products were identified as Plkl inhibitors and some synthetic Plkl inhibitors were developed by mimicking ATP and phosphopeptides, natural products binding to NCD and PBD respectively. This article not only reviews the progression of Plkl inhibitors binding to these two pockets, but also discusses diversity evolution and jump in the process of drug development using Plkl inhibitors as examples and how they impact on drug design and pharmacopbore modeling.
