Biomechanical forces in atherosclerosis-susceptible and -resistant regions of human vasculature differentially regulate endothelial vaso-protective phenotypes

Introduction Atherosclerosis is a potentially life-threatening disease of large arteries that is strongly associated with systemic risk factors such as hypercholesterolemia,hypertension,smoking,and diabetes. However,atherosclerosis develops as a

Anisotropic microtopography surface of chitosan scaffold regulating skin precursor-derived Schwann cells towards repair phenotype promotes neural regeneration

For repairing peripheral nerve and spinal cord defects,biomaterial scaffoid-based cell-therapy was emerged as an effective strategy,requiring the positive response of seed cells to biomaterial substrate and environment signals.Previous work highlighted that the imposed surface properties of scaffold could provide important guidance cues to adhered cells for polarization.However,the insufficiency of native Schwann cells and unclear cellular response mechanisms remained to be addressed.Given that,this study aimed to illuminate the micropatterned chitosan-film action on the rat skin precursor-derived Schwann cells(SKP-SCs).Chitosanfilm with different ridge/groove size was fabricated and applied for the SKP-SCs induction.Results indicated that SKP-SCs cultured on 30μm size microgroove surface showed better oriented alignment phenotype.Induced SKP-sCs presented similar genic phenotype as repair Schwann cells,increasing expression of c-Jun,neural cell adhesion molecule,and neurotrophic receptor p75.Moreover,SKP-SC-secretome was subjected to cytokine array GS67 assay,data indicated the regulation of paracrine phenotype,a panel of cytokines was verifed up-regulated at secreted level and gene expression level in induced SKP-SCs.These up-regulated cytokines exhibit a series of promotive neural regeneration functions,including cell survival,cell migration,cell proliferation,angiogenesis,axon growth,and cellular organization etc.through bioinformatics analysis.Furthermore,the effectively polarized SKP-SCs-sourced secretome,promoted the proliferation and migration capacity of the primarily cultured native rat Schwann cells,and augmented neurites growth of the cultured motoneurons,as well as boosted axonal regrowth of the axotomy-injured motoneurons.Taken together,SKP-SCs obtained pro-neuroregeneration phenotype in adaptive response to the anisotropic topography surface of chitosan-film,displayed the oriented parallel growth,the transition towards repair Schwann cell genic phenotype,and the enhanced paracrine effect on neural regeneration.This study provided novel insights into the potency of anisotropic microtopography surface to Schwann-like cells phenotype regulation,that facilitating to provide promising engineered cell-scaffold in neural injury therapies.

Arabidopsis SUMO protease ASP1 positively regulates flowering time partially through regulating FLC stability

The initiation of flowering is tightly regulated by the endogenous and environment signals, which is crucial for the reproductive success of flowering plants. It is well known that autonomous and vernalization pathways repress transcription of FLOWERING LOCUS C（FLC）, a focal floral repressor, but how its protein stability is regulated remains largely unknown. Here, we found that mutations in a novel Arabidopsis SUMO protease 1（ASP1） resulted in a strong late-flowering phenotype under long-days, but to a lesser extent under short-days. ASP1 localizes in the nucleus and exhibited a SUMO protease activity in vitro and in vivo. The conserved Cys-577 in ASP1 is critical for its enzymatic activity, as well as its physiological function in the regulation of flowering time. Genetic and gene expression analyses demonstrated that ASP1 promotes transcription of positive regulators of flowering, such as FT,SOC1 and FD, and may function in both CO-dependent photoperiod pathway and FLC-dependent pathways.Although the transcription level of FLC was not affected in the loss-of-function asp1 mutant, the protein stability of FLC was increased in the asp1 mutant. Taken together, this study identified a novel bona fide SUMO protease, ASP1,which positively regulates transition to flowering at least partly by repressing FLC protein stability.

SUMO E3 Ligases GmSIZ1a and GmSIZ1b regulate vegetative growth in soybean

SIZ1 is a small ubiquitin-related modifier（SUMO） E3 ligase that mediates post-translational SUMO modification of target proteins and thereby regulates developmental processes and hormonal and environmental stress responses in Arabidopsis. However,the role of SUMO E3 ligases in crop plants is largely unknown. Here, we identified and characterized two Glycine max（soybean） SUMO E3 ligases, GmSIZ1a and GmSIZ1b. Expression of GmSIZ1a and GmSIZ1b was induced in response to salicylic acid（SA）, heat, and dehydration treatment, but not in response to cold, abscisic acid（ABA）, and Na Cl treatment. Although GmSIZ1a was expressed at higher levels than GmSIZ1b, both genes encoded proteins with SUMO E3 ligase activity in vivo.Heterologous expression of GmSIZ1a or GmSIZ1b rescued the mutant phenotype of Arabidopsis siz1-2, including dwarfism, constitutively activated expression of pathogen-related genes, and ABA-sensitive seed germination.Simultaneous downregulation of GmSIZ1a and GmSIZ1b（GmSIZ1a/b） using RNA interference（RNAi）-mediated gene silencing decreased heat shock-induced SUMO conjugation in soybean. Moreover, GmSIZ1 RNAi plants exhibited reduced plant height and leaf size. However,unlike Arabidopsis siz1-2 mutant plants, flowering time and SA levels were not significantly altered in GmSIZ1 RNAi plants. Taken together, our results indicate that GmSIZ1a and GmSIZ1b mediate SUMO modification and positively regulate vegetative growth in soybean.

Expression of Ether à go-go 1 and its molecular mechamism of regulating the malignant phenotype of osteosarcoma

Objective To explore the expression of etheràgo-go1(Eag1)in human osteosarcoma and its molecular mechanisms of regulating the malignant phenotype of osteosarcoma.Methods The expression levels of Eag1 in osteosarcoma cell lines and human osteosarcoma tissues were detected by reverse transcription polymerase chain reaction(RT-PCR),western blot analysis and immunohistochemistry.The small interfering RNA(siRNA)was