Objective-Recent studies have illustrated that mesenchymal stem cells possess the potential to differentiate along an endothelial lineage, but the effect of shear on mesenchymal differentiation is unknown. Thus, we developed an in vitro shear stress system to examine the relationship between shear stress and the endothelial differentiation of a murine embryonic mesenchymal progenitor cell line, C3H/10T1/2. Methods and Results-The parallel plate system of fluid shear stress was used. Shear stress significantly induced expression of mature endothelial cell-specific markers in CH3H/10T1/2 cells such as CD31, von Willebrand factor, and vascular endothelial-cadherin at both the mRNA and protein levels with real-time polymerase chain reaction and immunofluorescence analyses, respectively. In addition, shear-induced augmentation of functional markers of the mature endothelial phenotype such as uptake of acetylated low-density lipoproteins and formation of capillary-like structures on Matrigel. Furthermore, shear stress significantly upregulated angiogenic growth factors while downregulating growth factors associated with smooth muscle cell differentiation. T he blood vessel wall is inherently subjected to and affected by the pulsatile hemodynamic stimulus of blood flow within the vascular lumen, and biomechanical forces intrinsically present as a result of this hemodynamic flow are believed to play an important role in vascular development, remodeling, and lesion formation. In particular, cells lining the vascular lumen are constantly subjected to shear stress, a frictional force at the apical endothelial surface exerted by blood flow. 1,2 Shear stress has been recognized as an important modulator of endothelial phenotype, morphology, gene expression, and, especially, differentiation. 3,4 See page 1761 Conclusions-ThisThe ability to influence or control endothelial cell differentiation would have implications for vasculogenesis (neovascularization), understanding the pathogenic physiology behind atherosclerotic lesion formation, use in vascular healing or repair, and use in tissue engineering applications; thus, recent studies have demonstrated the utility of shear stress in provoking endothelial progenitor cell (EPC) differentiation. 4,5 However, these studies have generally used a fairly heterogeneous starting precursor population. Furthermore, the overall small number of EPCs in circulation and the need for ex vivo expansion before use suggests that the EPC may not be the best progenitor for functional application. 6 Recent studies have illustrated that mesenchymal stem cells (MSCs) also possess the potential to differentiate along an endothelial lineage. 7,8 For example, Oswald et al demonstrated endothelial differentiation when MSCs were cultivated in 2% FCS and 50 ng/mL vascular endothelial growth factor (VEGF). 7 Additionally, other studies have revealed the contribution of MSCs to the formation of new vessels and improvements in cardiac function. 9,10 Thus, MSCs may hold the potential to differentiate along end...

Resistin induces human endothelial cell proliferation and migration, promotes capillary-like tube formation, upregulates the expression of VEGFRs and MMPs, and activates ERK1/2 and p38 pathways. Thus, resistin may play an important role in angiogenesis-associated vascular disorders.

The spliceostatin class of natural products was reported to be potent cytotoxic agents via inhibition of the spliceosome, a key protein complex in the biosynthesis of mature mRNA. As part of an effort to discover novel leads for cancer chemotherapy, we re-examined this class of compounds from several angles, including fermentation of the producing strains, isolation and structure determination of new analogues, and semisynthetic modification. Accordingly, a group of spliceostatins were isolated from a culture broth of Burkholderia sp. FERM BP-3421, and their structures identified by analysis of spectroscopic data. Semisynthesis was performed on the major components 4 and 5 to generate ester and amide derivatives with improved in vitro potency. With their potent activity against tumor cells and unique mode of action, spliceostatins can be considered potential leads for development of cancer drugs.

A series of novel antibiotics with activity against methicillin-resistant staphylococci and vancomycin-resistant enterococci has been purified, and their structures have been characterized using spectroscopic analyses and chemical conversions. These antibiotics, designated mannopeptimycins alpha-epsilon (1-5), are glycosylated cyclic hexapeptides containing two stereoisomers of an unprecedented amino acid, alpha-amino-beta-[4'-(2'-iminoimidazolidinyl)]-beta-hydroxypropionic acid (Aiha), as a distinguishing feature. The cyclic peptide core of these antibiotics is attached to a mannosyl monosaccharide moiety in 2 and to mannosyl monosaccharide and disaccharide moieties in 1, 3, 4, and 5. The presence and position of an isovaleryl group in the terminal mannose (Man-B) in 3-5 are critical for retaining antibacterial potency.

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