Study of the cytological features of bone marrow mesenchymal stem cells from patients with neuromyelitis optica.

Neuromyelitis optica (NMO) is a refractory autoimmune inflammatory disease of the central nervous system without an effective cure. Autologous bone marrow‑derived mesenchymal stem cells (BM‑MSCs) are considered to be promising therapeutic agents for this disease due to their potential regenerative, immune regulatory and neurotrophic effects. However, little is known about the cytological features of BM‑MSCs from patients with NMO, which may influence any therapeutic effects. The present study aimed to compare the proliferation, differentiation and senescence of BM‑MSCs from patients with NMO with that of age‑ and sex‑matched healthy subjects. It was revealed that there were no significant differences in terms of cell morphology or differentiation capacities in the BM‑MSCs from the patients with NMO. However, in comparison with healthy controls, BM‑MSCs derived from the Patients with NMO exhibited a decreased proliferation rate, in addition to a decreased expression of several cell cycle‑promoting and proliferation‑associated genes. Furthermore, the cell death rate increased in BM‑MSCs from patients under normal culture conditions and an assessment of the gene expression profile further confirmed that the BM‑MSCs from patients with NMO were more vulnerable to senescence. Platelet‑derived growth factor (PDGF), as a major mitotic stimulatory factor for MSCs and a potent therapeutic cytokine in demyelinating disease, was able to overcome the decreased proliferation rate and increased senescence defects in BM‑MSCs from the patients with NMO. Taken together, the results from the present study have enabled the proposition of the possibility of combining the application of autologous BM‑MSCs and PDGF for refractory and severe patients with NMO in order to elicit improved therapeutic effects, or, at the least, to include PDGF as a necessary and standard growth factor in the current in vitro formula for the culture of NMO patient‑derived BM‑MSCs

Protoporphyrinogen Oxidase Inhibitor: An Ideal Target for Herbicide Discovery

As the last common enzyme in the biosynthetic pathway leading to heme and chlorophyll, protoporphyrinogen oxidase (PPO; EC 1.3.3.4) is an ideal target for herbicide development. Currently, about 30 PPO inhibitors have been developed as agricultural herbicides. PPO inhibitors have displayed environmentally benign, but advantageous characteristics, including low toxicity, low effective concentration, broad herbicidal spectrum (active against both monocotyledon and dicotyledon weeds), quick onset of action, and long lasting effect. Over the last several years, great achievements have been made in revealing the structural biology of PPO. Five PPO crystal structures, four isolated in enzyme-inhibitor complexes and one in the native form, have been determined, including those from Nicotiana tabacum, Myxococcus Xanthus, Bacillus subtilis, and human. Although PPO inhibitors have been developed for over forty years, we continue to uncover exciting future prospects for novel PPO-inhibiting herbicides. In this review, we have summarized the structures of PPOs from plants, human, and bacteria; the interactions between PPOs and inhibitors; the quantitative structure–activity relationships of PPO inhibitors; and the molecular design of new PPO inhibitors