Ohioensin F suppresses TNF-α-induced adhesion molecule expression by inactivation of the MAPK, Akt and NF-κB pathways in vascular smooth muscle cells

AimsThe expression of cell adhesion molecules on vascular smooth muscle cells is central to leukocyte recruitment and progression of atherosclerotic disease. Ohioensin F, a chemical compound of the Antarctic moss Polyerichastrum alpinum, exhibited inhibitory activity against protein tyrosine phosphatase 1B and antioxidant activity. However, published scientific information regarding other biological activities and pharmacological function of ohioensin F is scarce. In the present study, we aimed to examine the in vitro effects of ohioensin F on the ability to suppress TNF-α-induced adhesion molecule expression in vascular smooth muscle cells (VSMCs).Main methodsThe inhibitory effect of ohioensin F on TNF-α-induced upregulation in expression of adhesion molecules was investigated by enzyme-linked immunosorbent assay, cell adhesion assay, RT-PCR, western blot analysis, immunofluorescence, and transfection and reporter assay, respectively.Key findingsPretreatment of VSMCs with ohioensin F at nontoxic concentrations of 0.1–10 μg/ml dose-dependently inhibited TNF-α-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). In addition, ohioensin F suppressed adhesion of THP-1 monocytes to TNF-α-stimulated VSMCs. Ohioensin F reduced TNF-α-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38, ERK, JNK and Akt. Finally, ohioensin F inhibited TNF-α-induced CAM mRNA expression and NK-κB translocation.SignificanceThese results suggest a new mechanism of ohioensin F's anti-inflammatory action, owing to the negative regulation of TNF-α-induced adhesion molecule expression, monocyte adhesion and ROS production in vascular smooth muscle cells. Our finding also supports ohioensin F as a potential pharmacological, anti-inflammatory molecule that has a protective effect on the atherosclerotic lesion.     

Hwanggeumchal sorghum induces cell cycle arrest, and suppresses tumor growth and metastasis through Jak2/STAT pathways in breast cancer xenografts

Background

Cancer is one of the highly virulent diseases known to humankind with a high mortality rate. Breast cancer is the most common cancer in women worldwide. Sorghum is a principal cereal food in many parts of the world, and is critical in folk medicine of Asia and Africa. In the present study, we analyzed the effects of HSE in metastatic breast cancer.

Methodology/Principal Findings

Preliminary studies conducted on MDA-MB 231 and MCF-7 xenograft models showed tumor growth suppression by HSE. Western blotting studies conducted both in vivo and in vitro to check the effect of HSE in Jak/STAT pathways. Anti-metastatic effects of HSE were confirmed using both MDA-MB 231 and MCF-7 metastatic animal models. These studies showed that HSE can modulate Jak/STAT pathways, and it hindered the STAT5b/IGF-1R and STAT3/VEGF pathways not only by down-regulating the expression of these signal molecules and but also by preventing their phosphorylation. The expression of angiogenic factors like VEGF, VEGF-R2 and cell cycle regulators like cyclin D, cyclin E, and pRb were found down-regulated by HSE. In addition, it also targets Brk, p53, and HIF-1α for anti-cancer effects. HSE induced G1 phase arrest and migration inhibition in MDA-MB 231 cells. The metastasis of breast cancer to the lungs also found blocked by HSE in the metastatic animal model.

Conclusions/Significance

Usage of HS as a dietary supplement is an inexpensive natural cancer therapy, without any side effects. We strongly recommend the use of HS as an edible therapeutic agent as it possesses tumor suppression, migration inhibition, and anti-metastatic effects on breast cancer.     

Intracellular calcium dynamics at the core of endocardial stationary spiral waves in Langendorff-perfused rabbit hearts

In vitro models of sustained monomorphic ventricular tachycardia (MVT) are rare and do not usually show spiral reentry on the epicardium. We hypothesized that MVT is associated with the spiral wave in the endocardium and that this stable reentrant propagation is supported by a persistently elevated intracellular calcium (Ca(i)) transient at the core of the spiral wave. We performed dual optical mapping of transmembrane potential (V(m)) and Ca(i) dynamics of the right ventricular (RV) endocardium in Langendorff-perfused rabbit hearts (n = 12). Among 64 induced arrhythmias, 55% were sustained MVT (>10 min). Eighty percent of MVT showed stationary spiral waves (>10 cycles, cycle length: 128 +/- 14.6 ms) in the endocardial mapped region, anchoring to the anatomic discontinuities. No reentry activity was observed in the epicardium. During reentry, the amplitudes of V(m) and Ca(i) signals were higher in the periphery and gradually decreased toward the core. At the core, maximal V(m) and Ca(i) amplitudes were 42.95 +/- 5.89% and 43.95 +/- 9.46%, respectively, of the control (P < 0.001). However, the trough of the V(m) and Ca(i) signals at the core were higher than those in the periphery, indicating persistent V(m) and Ca(i) elevations during reentry. BAPTA-AM, a calcium chelator, significantly reduced the maximal Ca(i) transient amplitude and prevented sustained MVT and spiral wave formation in the mapped region. These findings indicate that endocardial spiral waves often anchor to anatomic discontinuities causing stable MVT in normal rabbit ventricles. The spiral core is characterized by diminished V(m) and Ca(i) amplitudes and persistent V(m) and Ca(i) elevations during reentry.     

Quantification of emotion by nonlinear analysis of the chaotic dynamics of electroencephalograms during perception of 1/f music

The goal of this study is to quantify and determine the way in which the emotional response to music is reflected in the electrical activities of the brain. When the power spectrum of sequences of musical notes is inversely proportional to the frequency on a log-log plot, we call it 1/f music. According to previous research, most listeners agree that 1/f music is much more pleasing than white (1/f ⁰) or brown (1/f ²) music. Based on these studies, we used nonlinear methods to investigate the chaotic dynamics of electroencephalograms (EEGs) elicited by computer-generated 1/f music, white music, and brown music. In this analysis, we used the correlation dimension and the largest Lyapunov exponent as measures of complexity and chaos. We developed a new method that is strikingly faster and more accurate than other algorithms for calculating the nonlinear invariant measures from limited noisy data. At the right temporal lobe, 1/f music elicited lower values of both the correlation dimension and the largest Lyapunov exponent than white or brown music. We observed that brains which feel more pleased show decreased chaotic electrophysiological behavior. By observing that the nonlinear invariant measures for the 1/f distribution of the rhythm with the melody kept constant are lower than those for the 1/f distribution of melody with the rhythm kept constant, we could conclude that the rhythm variations contribute much more to a pleasing response to music than the melody variations do. These results support the assumption that chaos plays an important role in brain function, especially emotion. Received: 30 December 1996 / Accepted in revised form: 18 December 1997     

Heterologous expression of an RNA-binding protein affects flowering time as well as other developmental processes in <Emphasis Type="Italic">Solanaceae</Emphasis>

Flowering time in members of the Solanaceae plant family, such as pepper (Capsicum spp.) and tomato (Solanum lycopersicum), is an important agronomic trait for controlling shoot architecture and improving yield. To investigate the feasibility of flowering time regulation in tomato, an RNA-binding protein (RBP) encoding gene homologous to human Nucleolar protein interacting with the forkhead-associated (FHA) domain of pKI-67 (NIFK), CaRBP, was isolated from hot pepper. The function of CaRBP was determined in transgenic tomato. The deduced amino acid sequence includes an RNA recognition motif (RRM) and showed most similarity to the RRM present in a putative RBP encoded by human NIFK. CaRBP was highly expressed in the vegetative and reproductive tissues, such as leaves and fruits, respectively. Subcellular localization analysis indicated that CaRBP is a nucleolar protein. Heterologous expression of CaRBP under 35S promoter in tomato plants induced severe alteration of flowering with additional defects of vegetative organs. This floral retardation was associated with the alteration of SFT/SP3D and SlSOC1s as floral integrators. Furthermore, CaRBP reduces the expression levels of SlCOLs/TCOLs via changes in the expression of SlCDF3, SlFBHs, and SlFKF1s. This indicates a repressive effect of CaRBP on the regulation of flowering time in tomato. Overall, these results suggest that alteration in CaRBP expression levels may provide an effective means of controlling flowering time in day-neutral Solanaceae.