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Colon crypts are recognized as a mechanical and biochemical Turing patterning model. Colon epithelial Caco‐2 cell monolayer demonstrated 2D Turing patterns via force analysis of apical tight junction live cell imaging which illuminated actomyosin meshwork linking the actomyosin network of individual cells. Actomyosin forces act in a mechanobiological manner that alters cell/nucleus/tissue morphology. We observed the rotational motion of the nucleus in Caco‐2 cells that appears to be driven by actomyosin during the formation of a differentiated confluent epithelium. Single‐ to multi‐cell ring/torus‐shaped genomes were observed prior to complex fractal Turing patterns extending from a rotating torus centre in a spiral pattern consistent with a gene morphogen motif. These features may contribute to the well‐described differentiation from stem cells at the crypt base to the luminal colon epithelium along the crypt axis. This observation may be useful to study the role of mechanogenomic processes and the underlying molecular mechanisms as determinants of cellular and tissue architecture in space and time, which is the focal point of the 4D nucleome initiative. Mathematical and bioengineer modelling of gene circuits and cell shapes may provide a powerful algorithm that will contribute to future precision medicine relevant to a number of common medical disorders. [ABSTRACT FROM AUTHOR]

Long noncoding RNA SPRY4‐IT1 has been reported to promote melanoma cell growth and invasion, and to block apoptosis. The purpose of this study was to investigate the clinical significance of SPRY4‐IT1 in patients with malignant melanoma. The relative expression levels of SPRY4‐IT1 were measured in plasma samples from 70 patients and 79 healthy controls by quantitative reverse transcriptase polymerase chain reaction. SPRY4‐IT1 expression is high in melanoma patients but low in healthy controls, and is closely associated with tumor site and tumor stage. Elevated SPRY4‐IT1 significantly reduces overall survival rates of patients and is considered as an independent prognostic factor in patients with melanoma. The prognostic nomogram shows a good prediction of the probability of 5‐year overall survival of patients with melanoma (c‐index: 0.72). The calibration curve for the probability of survival presents good agreement between actual outcomes and predictive consequences. In summary, SPRY4‐IT1 may be a potential prognostic marker and a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cryptotanshinone (CTS) is a major bioactive diterpenoid isolated from Danshen, an eminent medicinal herb that is used to treat cardiovascular disorders in Asian medicine. However, it is not known whether CTS can prevent experimental atherosclerosis. The present study was designed to investigate the protective effects of CTS on atherosclerosis and its molecular mechanisms of action.Experimental Approach: Apolipoprotein E-deficient (ApoE(-/-)) mice, fed an atherogenic diet, were dosed daily with CTS (15, 45 mg kg(-1) day(-1)) by oral gavage. In vitro studies were carried out in oxidized LDL (oxLDL)-stimulated HUVECs treated with or without CTS.Key Results: CTS significantly attenuated atherosclerotic plaque formation and enhanced plaque stability in ApoE(-/-) mice by inhibiting the expression of lectin-like oxLDL receptor-1 (LOX-1) and MMP-9, as well as inhibiting reactive oxygen species (ROS) generation and NF-κB activation. CTS treatment significantly decreased the levels of serum pro-inflammatory mediators without altering the serum lipid profile. In vitro, CTS decreased oxLDL-induced LOX-1 mRNA and protein expression and, thereby, inhibited LOX-1-mediated adhesion of monocytes to HUVECs, by reducing the expression of adhesion molecules (intracellular adhesion molecule 1 and vascular cellular adhesion molecule 1). Furthermore, CTS inhibited NADPH oxidase subunit 4 (NOX4)-mediated ROS generation and consequent activation of NF-κB in HUVECs.Conclusions and Implications: CTS was shown to have anti-atherosclerotic activity, which was mediated through inhibition of the LOX-1-mediated signalling pathway. This suggests that CTS is a vasculoprotective drug that has potential therapeutic value for the clinical treatment of atherosclerotic cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Until 30 years ago, it had been considered that D-amino acids were excluded from living systems except for D-amino acids in the cell wall of microorganisms. However, D-amino acids, in the form of free amino acids, peptides and proteins, were recently detected in various living organisms from bacteria to mammals. The extensive distribution of bio-functional D-amino acids challenges the current concept of protein synthesis: more attention should be paid to the stereospecificity of the translation machine. Besides aminoacyl-tRNA synthetases, elongation factor Tu and some other mechanisms, D-Tyr-tRNATyr deacylases provide a novel checkpoint since they specifically recycle misaminoacylated D-Tyr-tRNATyr and some other D-aminoacyl-tRNAs. Their unique structure represents a new class of tRNA-dependent hydrolase. These unexpected findings have far-reaching implications for our understanding of protein synthesis and its origin. [Copyright &y& Elsevier]

Background: Kruppel-like factor 2 (KLF2) is an important zinc-finger transcription factor that maintains endothelial homeostasis by its anti-inflammatory, -thrombotic, -oxidative, and -proliferative effects in endothelial cells. In light of the potent vasoprotective effects of KLF2, modulating KLF2 expression or function could give rise to new therapeutic strategies to treat cardiovascular diseases., Methods and Results: High-throughput drug screening based on KLF2 promoter luciferase reporter assay was performed to screen KLF2 activators. Real-time PCR and western blot were used to detect gene and protein expression. Identified KLF2 activator was orally administered to ApoE -/- mice to evaluate anti-atherosclerotic efficacy. By screening 2400 compounds in the Spectrum library, we identified suberanilohydroxamic (SAHA) acid, also known as vorinostat as a pharmacological KLF2 activator through myocyte enhancer factor 2. We found that SAHA exhibited anti-inflammatory effects and attenuated monocyte adhesion to endothelial cells inflamed with tumor necrosis factor alpha. We further showed that the inhibitory effect of SAHA on endothelial inflammation and ensuing monocyte adhesion was KLF2 dependent using KLF2-deficient mouse lung endothelial cells or KLF2 small interfering RNA- depleted human endothelial cells. Importantly, we observed that oral administration of SAHA reduced diet-induced atherosclerotic lesion development in ApoE -/- mice without significant effect on serum lipid levels., Conclusions: These results demonstrate that SAHA has KLF2-dependent anti-inflammatory effects in endothelial cells and provide the proof of concept that KLF2 activation could be a promising therapeutic strategy for treating atherosclerosis., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)