Conditioned medium from mesenchymal stem cells (MSC-CM) may represent a promising alternative to MSCs transplantation, however, the low concentrations of growth factors in non-activated MSC-CM hamper its clinical application. Recent data indicated that the paracrine potential of MSCs could be enhanced by inflammatory factors. Herein, we pre-activated bone-marrow-derived MSCs under radiation-induced inflammatory condition (MSCIEC-6(IR)) and investigated the evidence and mechanism for the differential effects of MSC-CMIEC-6(IR) and non-activated MSC-CM on radiation-induced intestinal injury (RIII). Systemic infusion of MSC-CMIEC-6(IR), but not non-activated MSC-CM, dramatically improved intestinal damage and survival of irradiated rats. Such benefits may involve the modulation of epithelial regeneration and inflammation, as indicated by the regeneration of intestinal epithelial/stem cells, the regulation of the pro-/anti-inflammatory cytokine balance. The mechanism for the superior paracrine efficacy of MSCIEC-6(IR) is related to a higher secretion of regenerative, immunomodulatory and trafficking molecules, including the pivotal factor IGF-1, induced by TNF-α, IL-1β and nitric oxide partially via a heme oxygenase-1 dependent mechanism. Together, our findings suggest that pre-activation of MSCs with TNF-α, IL-1β and nitric oxide enhances its paracine effects on RIII via a heme oxygenase-1 dependent mechanism, which may help us to maximize the paracrine potential of MSCs.

SUMMARYGeminiviruses include a large number of single-stranded DNA viruses that are emerging as useful tools to dissect many fundamental processes in plant hosts. However, there have been no reports yet regarding the genetic dissection of the geminivirus-plant interaction. Here, a high-throughput approach was developed to screen Arabidopsis activation-tagged mutants which are resistant to geminivirus Beet severe curly top virus (BSCTV) infection. A mutant, lsb1 (less susceptible to BSCTV 1), was identified, in which BSCTV replication was impaired and BSCTV infectivity was reduced. We found that the three genes closest to the T-DNA were up-regulated in lsb1, and the phenotypes of lsb1 could only be recapitulated by the overexpression of GDU3 (GLUTAMINE DUMPER 3), a gene implicated in amino acid transport. We further demonstrated that activation of LSB1/GDU3 increased the expression of components in the salicylic acid (SA) pathway, which is known to counter geminivirus infection, including the upstream regulator ACD6. These data indicate that up-regulation of LSB1/GDU3 affects BSCTV infection by activating the SA pathway. This study thus provides a new approach to study of the geminivirus-host interaction.