Periodic explosive expansion of human retroelements associated with the evolution of the hominoid primate

Five retroelement families, L1 and L2 (long interspersed nuclear element, LINE), Alu and MIR (short interspersed nuclear element, SINE), and LTR (long terminal repeat), comprise almost half of the human genome. This genome-wide analysis on the time-scaled expansion of retroelements sheds light on the chronologically synchronous amplification peaks of each retroelement family in variable heights across human chromosomes. Especially, L1s and LTRs in the highest density on sex chromosomes Xq and Y, respectively, disclose peak activities that are obscured in autosomes. The periods of young L1, Alu, LTR, and old L1 peak activities calibrated based on sequence divergence coincide with the divergence of the three major hominoid divergence as well as early eutherian radiation while the amplification peaks of old MIR and L2 account for the marsupial-placental split. Overall, the peaks of autonomous LINE (young and old L1s and L2s) peaks and non-autonomous SINE (Alus and MIRs) have alternated repeatedly for 150 million years. In addition, a single burst of LTR parallels the Cretaceous-Tertiary (K-T) boundary, an exceptional global event. These findings suggest that the periodic explosive expansions of LINEs and SINEs and an exceptional burst of LTR comprise the genome dynamics underlying the macroevolution of the hominoid primate lineage.     

Effects of black cohosh on the plasminogen activator system in vascular smooth muscle cells

Objective

The rhizome of the Cimicifuga racemosa plant (commonly known as black cohosh) has been used for menopausal complaints. Studies regarding the cardiovascular effects of black cohosh are lacking. We investigated the effect of black cohosh on the plasminogen activator system in cultured vascular smooth muscle cells (VSMCs).

Methods

VSMCs were isolated from rat aortae. Expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) proteins were evaluated by Western blot analysis and enzyme-linked immunosorbent assay, respectively. The activities of PAI-1 and t-PA in the conditioned media were assessed by fibrin overlay zymography. A 40% 2-propanol extract of black cohosh was used.

Results

Black cohosh extract (BcEx) stimulated the protein expression of PAI-1, but it did not affect that of t-PA. Vitamin E, a potent antioxidant, inhibited the BcEx-induced increase in PAI-1 expression, while ICI 182,780, an estrogen receptor antagonist, had no effect. Fibrin overlay zymography revealed that BcEx increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA by inducing a binding to PAI-1.

Conclusions

BcEx induces PAI-1 protein expression in the VSMCs likely via an oxidant mechanism. It also stimulates the enzyme activity of PAI-1 and reduces that of free t-PA. These findings suggest that black cohosh might exert a negative influence on fibrinolysis.     

Assembly of collagen-binding peptide with collagen as a bioactive scaffold for osteogenesis in vitro and in vivo

Bioactive scaffolds inducing cell adhesion, differentiation have been premise for optimal formation of target tissue. Collagen has been employed as a tissue regenerative scaffold especially for bone regeneration and has been chemically surface-modified to present bioactivity. Herein, we show that peptide, denoted as collagen-binding motif (CBM, GLRSKSKKFRRPDIQYPDATDEDITSHM) identified from osteopontin (OPN) protein, was able to specifically bind collagen without chemical conjugation, while presenting apatite forming capability in vitro and in vivo. Collagen surface alone was not able to induce noticeable apatite nucleation however, mineralization was evident when assembled with CBM peptide, implying that the collagen-CBM assembly played a pivotal role in biomineralization. In vivo result further demonstrated that the CBM peptide in complex with material was able to induce bone formation by helping mineralization in the bone defect. Taken together, the CBM peptide herein and its assembly with collagen can be applied as an inducer of biomineralization as well as a bioactive scaffold for bone regeneration.     

Naringenin stimulates cholecystokinin secretion in STC-1 cells

BACKGROUND/OBJECTIVES

Cholecystokinin (CCK), a hormone or neuropeptide, is secreted in response to intraluminal nutrients by enteroendocrine I-cells of the intestine and has important physiological actions related to appetite regulation and satiety. The stimulation on CCK secretion from the intestine is of potential relevance for body weight management. Naringenin (4'',5,7-trihydroxyflavanone) and its glycoside naringin (naringenin 7-rhamnoglucoside) have been reported to have many biological functions. In the current study, we investigated the question of whether naringenin and naringin could stimulate CCK secretion and then examined the mechanisms involved in CCK release.

MATERIALS/METHODS

STC-1 cells were used as a model of enteroendocrine cells. CCK release and changes in intracellular Ca²⁺ ([Ca²⁺]_i) were measured after incubation of cells with naringenin and naringin for 1 h.

RESULTS

Naringenin caused significant (P < 0.05) stimulation of CCK secretion, but naringin did not. In addition, regarding the secretory mechanisms, naringenin-induced CCK secretion involved increases in [Ca²⁺]_i, influx of extracellular Ca²⁺, at least in part, and activation of TRP channels, including TRPA1.

CONCLUSION

Findings of this study suggest that naringenin could have a role in appetite regulation and satiety.     

Cerebral Cortex Changes in Basketball Players

BackgroundPlastic changes to brain structure and function have been reported in elite athletes of various sports. Interestingly, different regions of the brain were engaged according to the type of sports analyzed. Our laboratory reported no difference in total cerebellar volume of basketball players compared to that in the control group using the manual segmentation method. Further detailed analyses showed that elite basketball players had increased volume of the striatum and vermian lobules VI–VII of the cerebellum. We analyzed the brain magnetic resonance imaging (MRI) of basketball players to understand their cerebral cortical plasticity through automatic analysis tools for MRI.MethodsBrain MRI data were collected from 19 male university basketball players and 20 age-, sex-, and height-matched control groups. In order to understand the changes in the cerebral cortices of basketball players, we employed automated MRI brain analysis techniques, including voxel-based morphometry (VBM) and surface-based morphometry (SBM).ResultsVBM showed increased gray and white matter volume in both precentral gyri, paracentral lobules and increased gray matter volume in the right anterior superior temporal gyrus. SBM revealed a left dominant increase in both pericentral gyri. Fractal dimensional analysis showed an increase in the area of both precentral gyri, the left subcallosal gyrus, and the right posterior cingulate gyrus. These results suggest a significant role not only for the primary motor cortex, but also for the cingulate gyrus during basketball.ConclusionPlastic changes of both precentral gyri, the pericentral area, paracentral lobules, and the right superior temporal gyrus were observed in elite basketball players. There was a strong increase of fractal complexity in both precentral gyri and a weak increase in the right posterior cingulate gyrus and left collateral gyrus. In this study, plastic regions linked to functional neuroanatomy were related to the competence required to play basketball.     

Radix angelica elicits both nitric oxide-dependent and calcium influx-mediated relaxation in rat aorta

This study examined the vascular relaxation produced by Radix Angelica (AG; Dong Quai) and its possible mechanisms in isolated rat aortic rings precontracted with norepinephrine. The butanolic fraction (AgBt) of the crude extract of AG causes gradual endothelium-independent relaxation, which was unaffected by five different potassium channel inhibitors. AgBt attenuated the CaCl2-induced vasoconstriction in high-potassium depolarized medium; this required less than one-tenth the concentration needed to elicit vascular relaxation. An aqueous fraction (AgDw) of the crude extract induced transient acute relaxation, which was virtually abolished by endothelial ablation and pretreatment with L-NNA. L-Arginine fully reversed the action of L-NNA. Methylene blue and atropine significantly attenuated the relaxation, but indomethacin did not. Ferulic acid, the main active component in AG, relaxed both endothelium-intact and -denuded rings, while L-NNA, methylene blue, or atropine did not modify the relaxation. Ferulic acid also did not attenuate the CaCl2-induced contraction in high-potassium depolarized medium. In conclusion, Radix Angelica leads to both endothelium-dependent and -independent relaxation of isolated rat aorta. Increased formation of NO might contribute to the endothelium-mediated relaxation, while inhibition of the calcium influx might be an important mechanism in direct smooth muscle relaxation. A substance other than ferulic acid might create these effects.     

(-)-Epicatechin 3-O-gallate ameliorates the damages related to peroxynitrite production by mechanisms distinct from those of other free radical inhibitors

This study was carried out to elucidate whether the protective activity of (-)-epicatechin 3-O-gallate (ECg) against excessive peroxynitrite (ONOO(-)) production, is distinct from the activity of several well-known free radical inhibitors, the ONOO(-) inhibitors ebselen and uric acid, the superoxide anion (O(2)(-)) scavenger copper zinc superoxide dismutase (CuZnSOD) and the selective inducible nitric oxide synthase inhibitor L-N(6)-(1-iminoethyl)lysine hydrochloride (L-NIL). To generate ONOO(-), male Wistar rats (n = 6/group) were subjected to ischaemia-reperfusion process together with lipopolysaccharide (LPS) injection. Although ECg did not scavenge the ONOO(-) precursors nitric oxide (NO) and O(2)(-), it reduced the 3-nitrotyrosine level, a property similar to that of uric acid, but distinct from L-NIL. In addition, the elevation in myeloperoxidase activity was reversed by the administration of ECg, uric acid and SOD, but not by that of L-NIL. Furthermore, ECg was the more potent scavenger of the ONOO(-) decomposition product, the hydroxyl radical (*OH), than any other free radical inhibitor tested. The LPS plus ischaemia-reperfusion process resulted in renal dysfunction, estimated by measuring the parameters of renal function--serum urea nitrogen and creatinine levels. However, administration of ECg ameliorated renal dysfunction more than that of the other free radical inhibitors. Moreover, ECg reduced the excessive uric acid level, while the others did not, suggesting a property of ECg distinct from the others. Furthermore, proteinuria, which was demonstrated by the low- and high-molecular weight (LMW and HMW) protein bands of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis pattern, caused by LPS plus ischaemia-reperfusion, was attenuated by administration of ECg and L-NIL, after which the HMW band intensities decreased and LMW protein bands were absent. This study indicates that, in an in-vivo model of ONOO(-) generation, ECg, L-NIL and uric acid exert stronger protective activity against ONOO(-)-induced oxidative damage than SOD and ebselen, and that the mechanism whereby ECg protects against ONOO(-) is distinct from that of L-NIL or uric acid.     

Protection by the Chinese prescription Wen-Pi-Tang against renal tubular LLC-PK1 cell damage induced by 3-morpholinosydnonimine

We investigated the effects of Wen-Pi-Tang extract on the protective mechanisms of renal tubular LLC-PK1 cells, as renal tubular cells are the most vulnerable renal tissue to oxidative stress. Exposure to 800 microM 3-morpholinosydnonimine (SIN-1) resulted in a marked increase in cellular peroxynitrite (ONOO-), which converted nonfluorescent dihydrorhodamine 123 to fluorescent rhodamine 123, a detectable probe for the long-lived ONOO-. In addition, it resulted in apoptotic cell death, assessed by a DNA fragmentation assay. However, treatment with Wen-Pi-Tang extract, at concentrations of 50 and 100 microg mL(-1) together with SIN-1 protected renal tubular cells against ONOO- through scavenging ONOO- and inhibiting apoptotic cell death in a dose-dependent manner. Moreover, treatment with Wen-Pi-Tang extract both before and after exposure to SIN-1 was also protective: it reduced cellular ONOO- levels, increased cell viability and decreased the DNA fragmentation rate. These results suggest that Wen-Pi-Tang would have protective activity against ONOO- -induced renal tubular injury through the inhibition of ONOO- production and apoptotic cell death by both preventing and treating renal injury. Furthermore, morphological characteristics of apoptosis were observed in SIN-1 treated tubular cells, while the addition of Wen-Pi-Tang extract with SIN-1 attenuated these morphological changes. ONOO- generated by SIN-1 also disturbed the cell cycle by decreasing the cellular G2/M phase ratio, while Wen-Pi-Tang extract regulated the cell cycle by G2/M phase arrest.     

The inhibitory effects of 12 medicinal plants and their component compounds on lipid peroxidation

The antioxidative activities of 12 medicinal plants and the compounds isolated from them were investigated using the thiocyanate method to evaluate inhibitory effects on lipid peroxidation in the linoleic acid system. The peroxide levels gradually increased during incubation in the presence of linoleic acid over 3 days, and most of the plants inhibited lipid peroxidation. In particular, of the plants tested, Cudrania tricuspidata, Zanthoxylum piperitum, Houttuynia cordata and Ulmus parvifolia reduced lipid peroxidation more effectively as lipid peroxidation progressed, resulting in inhibition of about 80% relative to the control value by the 3rd day of incubation. In addition, the polyphenols isolated from the plants also showed marked and dose-dependent inhibitory effects on lipid peroxidation. The compounds with the strongest activities were 3,4-dihydroxylbenzoic acid, quercetin, the quercetin glycosides quercetin-3-O-beta-D-galactoside, quercetin-3-O-alpha-L-rhamnoside, quercetin-3-O-beta-D-glucoside and quercetin-3-O-rutinose, catechin, gallic acid, methyl gallate and rosamultin isolated from Zanthoxylum piperitum, Houttuynia cordata, Rosa rugosa and Cedrela sinensis. Moreover, quercetin glycosides showed stronger activity than quercetin, suggesting that glycosylation increases the antioxidative activity of quercetin. Our results indicate that the medicinal plants and their polyphenols show promise as therapeutic agents for various disorders involving free radical reactions.