IgAN was the most common primary GN, and MCD was the most common cause of nephrotic syndrome. In the 5-year quartile comparison, the relative frequency of IgAN increased, while the relative frequency of MCD and MPGN decreased significantly during the past 20 years.

The glycolipid antibiotic rhamnolipid B isolated from Pseudomonas aeruginosa strain B5 was evaluated for in vitro antifungal activity and in vivo control against phytophthora blight and anthracnose under glasshouse conditions. Rhamnolipid B showed antifungal activity against Cercospora kikuchii, Cladosporium cucumerinum, Colletotrichum orbiculare, Cylindrocarpon destructans, Magnaporthe grisea and Phytophthora capsici. Microscopic observation revealed that the high level of antifungal activity (10 mg ml À1 ) against P capsici was mainly due to a lytic effect on zoospores. Zoospore lysis began in the presence of 10 mg ml À1 of rhamnolipid B and most of the zoospores were collapsed at 25 mg ml À1 . Rhamnolipid B showed inhibitory activity against the germination of zoospores and hyphal growth of P capsici at concentrations of 50 mg ml À1 . Spore germination of the anthracnose plant pathogen C orbiculare was also inhibited in the presence of 50 mg ml À1 of rhamnolipid B, although hyphal growth was not affected at this concentration. In the glasshouse, the ef®cacy of rhamnolipid B against phytophthora blight was similar to that of metalaxyl on pepper plants when treated just before inoculation with P capsici. Treatment with either at 500 mg ml À1 completely protected pepper plants from phytophthora blight. Rhamnolipid B also suppressed the development of C orbiculare infection on leaves of cucumber plants.

The pikromycin biosynthetic gene cluster contains the pikAV gene encoding a type II thioesterase (TEII). TEII is not responsible for polyketide termination and cyclization, and its biosynthetic role has been unclear. During polyketide biosynthesis, extender units such as methylmalonyl acyl carrier protein (ACP) may prematurely decarboxylate to generate the corresponding acyl-ACP, which cannot be used as a substrate in the condensing reaction by the corresponding ketosynthase domain, rendering the polyketide synthase module inactive. It has been proposed that TEII may serve as an "editing" enzyme and reactivate these modules by removing acyl moieties attached to ACP domains. Using a purified recombinant TEII we have tested this hypothesis by using in vitro enzyme assays and a range of acyl-ACP, malonyl-ACP, and methylmalonyl-ACP substrates derived from either PikAIII or the loading didomain of DEBS1 (6- Polyketides are a large and structurally diverse class of natural products that possess a wide range of biological activities (1). These compounds are used throughout medicinal and agricultural fields as antimicrobials, immunosuppressants, antiparasitics, and anticancer agents. Despite their structural diversity, polyketides are assembled by a common mechanism of decarboxylative condensations of simple malonate derivatives by polyketide synthases (PKSs) 1 in a manner very similar to fatty acid biosynthesis (2, 3). Type I PKSs are a family of PKSs that are analogous to vertebrate fatty acid synthase that catalyze the biosynthesis of the polyketide moieties of various secondary metabolites in Streptomyces (4 -6). They are gigantic multifunctional modular proteins. Each module is responsible for one cycle of polyketide chain elongation and contains a set of discrete catalytic domains of ketosynthase (KS), acyltransferase (AT), and acyl carrier protein (ACP). Ketoreductase, dehydratase (DH), and enoyl reductase domains may also be present, allowing structural variation in the level of processing of the ␤-ketoacyl chain (4, 6). The fully extended polyketide chain bound to the PKS as an acyl-ACP thioester is often released and cyclized by a thioesterase domain (TEI) covalently linked to the last extending module of the PKS (7).In many cases, additional genes encoding a TE have been found within a polyketide biosynthetic gene cluster, for example, the tylosin PKS of Streptomyces fradiae (8), pikromycin PKS of Streptomyces venezuelae (5), rifamycin PKS of Amycolatopsis mediterranei (9), and the erythromycin PKS (DEBS) of Saccharopolyspora erythraea (10). These genes encoding a discrete protein were named as TEII to differentiate from the chain releasing TEI domains in modular polyketide synthases. Discrete TEII enzymes are also associated with bacterial nonribosomal peptide synthases, responsible for the production of macrocyclic peptide compounds (11), and animal fatty acid synthases (12). Sequence analysis has revealed that these thioesterases are probably structurally and evolutionarily related (13). They have a common...

We recently demonstrated the use of in vitro expanded kidney-derived mesenchymal stem cells (KMSC) protected peritubular capillary endothelial cells in acute renal ischemia-reperfusion injury. Herein, we isolated and characterized microparticles (MPs) from KMSC. We investigated their in vitro biologic effects on human endothelial cells and in vivo renoprotective effects in acute ischemia-reperfusion renal injury. MPs were isolated from the supernatants of KMSC cultured in anoxic conditions in serum-deprived media for 24 hours. KMSC-derived MPs demonstrated the presence of several adhesion molecules normally expressed on KMSC membranes, such as CD29, CD44, CD73, α4, 5, and 6 integrins. Quantitative real time PCR confirmed the presence of 3 splicing variants of VEGF-A (120, 164, 188), bFGF and IGF-1 in isolated MPs. MPs labeled with PKH26 red fluorescence dye were incorporated by cultured human umbilical vein endothelial cells (HUVEC) via surface molecules such as CD44, CD29, and α4, 5, and 6 integrins. MP dose dependently improved in vitro HUVEC proliferation and promoted endothelial tube formation on growth factor reduced Matrigel. Moreover, apoptosis of human microvascular endothelial cell was inhibited by MPs. Administration of KMSC-derived MPs into mice with acute renal ischemia was followed by selective engraftment in ischemic kidneys and significant improvement in renal function. This was achieved by improving proliferation, of peritubular capillary endothelial cell and amelioration of peritubular microvascular rarefaction. Our results support the hypothesis that KMSC-derived MPs may act as a source of proangiogenic signals and confer renoprotective effects in ischemic kidneys.

Regulatory T cells (Tregs) can suppress immunologic damage in renal ischemiareperfusion injury (IRI), but the isolation and ex vivo expansion of these cells for clinical application remains challenging. Here, we investigated whether the IL-2/ anti-IL-2 complex (IL-2C), a mediator of Treg expansion, can attenuate renal IRI in mice. IL-2C administered before bilateral renal IRI induced Treg expansion in both spleen and kidney, improved renal function, and attenuated histologic renal injury and apoptosis after IRI. Furthermore, IL-2C administration reduced the expression of inflammatory cytokines and attenuated the infiltration of neutrophils and macrophages in renal tissue. Depletion of Tregs with anti-CD25 antibodies abrogated the beneficial effects of IL-2C. However, IL-2C-mediated renal protection was not dependent on either IL-10 or TGF-b. Notably, IL-2C administered after IRI also enhanced Treg expansion in spleen and kidney, increased tubular cell proliferation, improved renal function, and reduced renal fibrosis. In conclusion, these results indicate that IL-2C-induced Treg expansion attenuates acute renal damage and improves renal recovery in vivo, suggesting that IL-2C may be a therapeutic strategy for renal IRI.

Our study revealed that RRF and diabetes were risk factors for peritonitis. These results suggest that preservation of RRF should be viewed as a protective strategy to reduce peritonitis.

No abstract

IntroductionMicroparticles (MPs) derived from kidney-derived mesenchymal stem cells (KMSCs) have recently been reported to ameliorate rarefaction of peritubular capillaries (PTC) in ischemic kidneys via delivery of proangiogenic effectors. This study aimed to investigate whether KMSC-derived MPs show anti-fibrotic effects by ameliorating endothelial-to-mesenchymal transition (EndoMT) in human umbilical vein endothelial cells (HUVEC) in vitro and by preserving PTC in kidneys with unilateral ureteral obstruction (UUO) in vivo.MethodsMPs isolated from the supernatants of KMSC were co-cultured with HUVEC to assess their in vitro biologic effects on endothelial cells. Mice were treated with MPs via the tail vein after UUO injury to assess their anti-fibrotic and PTC sparing effects. Renal tubulointerstitial damage and inflammatory cell infiltration were examined with Masson’s trichrome, F4/80 and α-smooth muscle actin (α-SMA) staining and PTC rarefaction index was determined by CD31 staining.ResultsKMSC-derived MPs significantly ameliorated EndoMT and improved in vitro proliferation of TGF-β1 treated HUVEC. In vivo administration of KMSC-derived MPs significantly inhibited EndoMT of PTC endothelial cells and improved PTC rarefaction in UUO kidneys. Furthermore, administration of KMSC-derived MPs inhibited inflammatory cell infiltration as well as tubulointerstitial fibrosis in UUO mice as demonstrated by decreased F4/80 and α-SMA-positive cells and Masson’s trichrome staining, respectively.ConclusionsOur results suggest that KMSC-derived MPs ameliorate PTC rarefaction via inhibition of EndoMT and protect against progression of renal damage by inhibiting tubulointerstitial fibrosis.