Longevity, tumor, and physical vitality in rats consuming ginsenoside Rg1.

Background: Effects of the major ginsenoside Rg1 on mammalian longevity and physical vitality are rarely reported. Purpose: To examine longevity, tumor, and spontaneous locomotor activity in rats consuming Rg1. Methods: A total of 138 Wistar rats were randomized into 2 groups: control (N = 69) and Rg1 (N = 69). Rg1 (0.1 mg/kg per day) were orally supplemented from 6 months of age until natural death. Spontaneous mobility was measured by video-tracking together with body composition (dual energy x-ray absorptiometry) and inflammation markers at 5, 14, 21, and 28 months of age. Results: No significant differences in longevity (control: 706 days; Rg1: 651 days, p = 0.77) and tumor incidence (control: 19%; Rg1: 12%, p = 0.24) were observed between the two groups. Movement distance in the control group declined significantly by ∼60% at 21 months of age, together with decreased TNF-α (p = 0.01) and increased IL-10 (p = 0.02). However, the movement distance in the Rg1 group was maintained ∼50% above the control groups (p = 0.01) at 21 months of age with greater magnitudes of TNF-α decreases and IL-10 increases. Glucose, insulin, and body composition (bone, muscle and fat percentages) were similar for both groups during the entire observation period. Conclusion: The results of the study suggest a delay age-dependent decline in physical vitality during late life by lifelong Rg1 consumption. This improvement is associated with inflammatory modulation. Significant effects of Rg1 on longevity and tumorigenesis were not observed.

Association between serum uric acid level and bone mineral density at multiple skeletal sites in middle-aged and elderly men: a cross-sectional study of a healthy population in Taiwan.

This study revealed that serum uric acid (sUA) levels were not associated with bone mineral density (BMD) at different skeletal sites in middle-aged and elderly men, even adjusting for confounding variables. Nevertheless, a positive association was only found between sUA levels and BMD at all skeletal sites in the normal BMI group. INTRODUCTION: Previous studies have reported an association between serum uric acid (sUA) levels and bone mineral density (BMD). However, their findings are controversial and limited to adult men in the general population. This study was aimed at examining the association between sUA levels and BMD at multiple skeletal sites in middle-aged and elderly men. METHODS: A cross-sectional analysis of BMD at different skeletal sites and sUA levels was conducted on 918 men (age: 50.83 ± 7.95) using data from the Ditmanson Research Database. The participants were categorized into four groups based on quartiles of the sUA level, and BMD were assessed using dual-energy X-ray absorptiometry. Multivariate linear regression models were utilized to investigate the association between sUA levels and BMD. Further, subgroup analyses were performed. RESULTS: After adjusting for potential confounding factors, sUA as a continuous variable was significantly associated with BMD at the femoral neck only (ß, 95% confidence interval: 0.007 [0.001-0.013]). However, in the categorical analysis, no significant differences were detected in terms of BMD at different skeletal sites across the different sUA quartile groups. Moreover, if the body mass index (BMI) was < 24 kg/m2 for each unit increase in sUA level, the spine, femoral neck, and total hip BMD increased by 0.014, 0.013, and 0.015 g/cm2, respectively. CONCLUSION: The sUA level was not associated with BMD at different skeletal sites in middle-aged and elderly men. Nevertheless, a positive association was only found between sUA levels and BMD at all skeletal sites in the normal weight group.

Longitudinal investigation of ischemic stroke using magnetic resonance imaging: Animal model.

BACKGROUND: Arterial embolism is a major cause of ischemic stroke. Currently, digital subtraction angiography (DSA) is the gold standard in clinical arterial embolization examinations. However, it is invasive and risky. OBJECTIVE: This study aims to longitudinally assess the progression of carotid artery embolism in middle cerebral artery occlusion animal model (MCAO) using magnetic resonance imaging (MRI) techniques. METHODS: Turbo spin echo (TSE), time of flight magnetic resonance angiography (TOF-MRA) and diffusion weighted magnetic resonance imaging (DWI) were used to evaluate the image characteristics of cerebral tissues at 1, 2, 3, 7, 14, 21 and 28 days after MCAO microsurgery on Sprague-Dawley (SD) rats. Quantitative analysis was performed and compared in MCAO hemisphere and contralateral normal hemisphere. Furthermore, pathologic section using triphenyl tetrazolium chloride (TTC) stain was performed as well. RESULTS: TOF-MRA showed carotid signal void in the embolism side, which is evidence of artery occlusion. The used MRI techniques showed that edema gradually dissipated within one week, but there was no significant change afterwards. The time-varying signal intensity of MRI techniques in MCAO hemisphere changed significantly, but there were no significant changes in contralateral normal hemisphere. Cerebral injury was also confirmed by analysis of pathology images. CONCLUSIONS: The MCAO animal model was successfully established on SD rats using the microsurgery to assess arterial embolization of intracranial tissue injury.

The SLOW GROWTH3 Pentatricopeptide Repeat Protein Is Required for the Splicing of Mitochondrial NADH Dehydrogenase Subunit7 Intron 2 in Arabidopsis.

Mitochondria play an important role in maintaining metabolic and energy homeostasis in the cell. In plants, impairment in mitochondrial functions usually has detrimental effects on growth and development. To study genes that are important for plant growth, we have isolated a collection of slow growth (slo) mutants in Arabidopsis (Arabidopsis thaliana). One of the slo mutants, slo3, has a significant reduction in mitochondrial complex I activity. The slo3 mutant has a four-nucleotide deletion in At3g61360 that encodes a pentatricopeptide repeat (PPR) protein. The SLO3 protein contains nine classic PPR domains belonging to the P subfamily. The small deletion in the slo3 mutant changes the reading frame and creates a premature stop codon in the first PPR domain. We demonstrated that the SLO3-GFP is localized to the mitochondrion. Further analysis of mitochondrial RNA metabolism revealed that the slo3 mutant was defective in splicing of NADH dehydrogenase subunit7 (nad7) intron 2. This specific splicing defect led to a dramatic reduction in complex I activity in the mutant as revealed by blue native gel analysis. Complementation of slo3 by 35S:SLO3 or 35S:SLO3-GFP restored the splicing of nad7 intron 2, the complex I activity, and the growth defects of the mutant. Together, these results indicate that the SLO3 PPR protein is a splicing factor of nad7 intron 2 in Arabidopsis mitochondria.

The optimal extracting process, manufacturing technique and biological evaluation of Lithospermum erythrorhizon microcapsules.

Lithospermum erythrorhizon has been proved to be anti-inflammatory, by recent studies. This study extracts L. erythrorhizon with ethanol at various solid-liquid ratios (1:4, 1:6, 1:8, and 1:12), extraction temperatures (40°C, 50°C, and 60°C), and extraction times (4, 24 and 36h) in order to determine the optimal parameters. The optimal parameters are extracted and condensed into L. erythrorhizon extract; then the antibacterial property and cell compatibility of L. erythrorhizon extract are evaluated with various concentrations of L. erythrorhizon extract solution and different weights of L. erythrorhizon extract powder, respectively. The concentrations of solution are 0.1mg/ml, 0.5mg/ml, 1.0mg/ml, and 2.0mg/ml and ethanol is chosen as the solvent, and different weights of powder are varied as 0.1mg, 1.0mg, 2.0mg, and 10mg. The cell viability test and animal study are performed on L. erythrorhizon microcapsules. The experiment results show that sodium alginate/pectin L. erythrorhizon (SPL) microcapsules possess a 120-hour drug release. The results of cell viability and animal study show that the L. erythrorhizon microcapsules (SPL) have good cell viability (99%) and can help in the wound healing process (the wound size reduction reaches 91.3% on Day 11).

Genome-Wide Analysis of Heat-Sensitive Alternative Splicing in Physcomitrella patens.

Plant growth and development are constantly influenced by temperature fluctuations. To respond to temperature changes, different levels of gene regulation are modulated in the cell. Alternative splicing (AS) is a widespread mechanism increasing transcriptome complexity and proteome diversity. Although genome-wide studies have revealed complex AS patterns in plants, whether AS impacts the stress defense of plants is not known. We used heat shock (HS) treatments at nondamaging temperature and messenger RNA sequencing to obtain HS transcriptomes in the moss Physcomitrella patens. Data analysis identified a significant number of novel AS events in the moss protonema. Nearly 50% of genes are alternatively spliced. Intron retention (IR) is markedly repressed under elevated temperature but alternative donor/acceptor site and exon skipping are mainly induced, indicating differential regulation of AS in response to heat stress. Transcripts undergoing heat-sensitive IR are mostly involved in specific functions, which suggests that plants regulate AS with transcript specificity under elevated temperature. An exonic GAG-repeat motif in these IR regions may function as a regulatory cis-element in heat-mediated AS regulation. A conserved AS pattern for HS transcription factors in P. patens and Arabidopsis (Arabidopsis thaliana) reveals that heat regulation for AS evolved early during land colonization of green plants. Our results support that AS of specific genes, including key HS regulators, is fine-tuned under elevated temperature to modulate gene regulation and reorganize metabolic processes.

Auditory spectral integration in the perception of static vowels.

PURPOSE: To evaluate potential contributions of broadband spectral integration in the perception of static vowels. Specifically, can the auditory system infer formant frequency information from changes in the intensity weighting across harmonics when the formant itself is missing? Does this type of integration produce the same results in the lower (first formant [F1]) and higher (second formant [F2]) regions? Does the spacing between the spectral components affect a listener's ability to integrate the acoustic cues? METHOD: Twenty young listeners with normal hearing identified synthesized vowel-like stimuli created for adjustments in the F1 region (/Λ/-/α/, /i/-/ε/) and in the F2 region (/Λ/-/æ/). There were 2 types of stimuli: (a) 2-formant tokens and (b) tokens in which 1 formant was removed and 2 pairs of sine waves were inserted below and above the missing formant; the intensities of these harmonics were modified to cause variations in their spectral center of gravity (COG). The COG effects were tested over a wide range of frequencies. RESULTS: Obtained patterns were consistent with calculated changes to the spectral COG, in both the F1 and F2 regions. The spacing of the sine waves did not affect listeners' responses. CONCLUSION: The auditory system may perform broadband integration as a type of auditory wideband spectral analysis.

Auditory spectral integration in the perception of diphthongal vowels.

This study considers an operation of an auditory spectral integration process which may be involved in perceiving dynamic time-varying changes in speech found in diphthongs and glide-type transitions. Does the auditory system need explicit vowel formants to track the dynamic changes over time? Listeners classified diphthongs on the basis of a moving center of gravity (COG) brought about by changing intensity ratio of static spectral components instead of changing an F2. Listeners were unable to detect COG movement only when the F2 change was small (160 Hz) or when the separation between the static components was large (4.95 bark).

The long-distance signaling of mineral macronutrients.

In response to varying nutrient availability in soil, plants display a high degree of physiological and developmental plasticity that relies on both local and systemic signaling pathways to coordinate the expression of genes involved in adaptive responses. The integration of these responses at the whole-plant level requires long-distance signaling mechanisms communicating the information between the two indispensable organs, the shoot and the root, which respectively provide photosynthates and mineral nutrients. Although such long-distance signaling is not well understood at the molecular level, several molecules, including hormones, sugars, and nutrients themselves or their metabolites, have been suggested to function as the systemic signals. Moreover, recent discoveries of the phloem-mobile microRNA399s as key components mediating the plant responses to phosphorus stress reveal a novel biological role of small RNA in the long-distance signaling of nutrient status.

Chloroplast localization of methylerythritol 4-phosphate pathway enzymes and regulation of mitochondrial genes in ispD and ispE albino mutants in Arabidopsis.

Plant isoprenoids are derived from two independent pathways, the cytosolic mevalonate pathway and the plastid methylerythritol 4-phosphate (MEP) pathway. We used green fluorescent fusion protein assays to demonstrate that the Arabidopsis MEP pathway enzymes are localized to the chloroplast. We have also characterized three Arabidopsis albino mutants, ispD-1, ispD-2 and ispE-1, which have T-DNA insertions in the IspD and IspE genes of the MEP pathway. Levels of photosynthetic pigments are almost undetectable in these albino mutants. Instead of thylakoids, the ispD and ispE mutant chloroplasts are filled with large vesicles. Impairments in chloroplast development and functions may signal changes in the expression of nuclear, chloroplast and mitochondrial genes. We used northern blot analysis to examine the expression of photosynthetic and respiratory genes in the ispD and ispE albino mutants. Steady-state mRNA levels of nucleus- and chloroplast-encoded photosynthetic genes are significantly decreased in the albino mutants. In contrast, transcript levels of nuclear and mitochondrial genes encoding subunits of the mitochondrial electron transport chain are increased or not affected in these mutants. Genomic Southern blot analysis revealed that the DNA amounts of mitochondrial genes are not enhanced in the ispD and ispE albino mutants. These results support the notion that the functional state of chloroplasts may affect the expression of nuclear and mitochondrial genes. The up-regulation of mitochondrial genes in the albino mutants is not caused by changes of mitochondrial DNA copy number in Arabidopsis.

Synthesis and anticancer activity of benzyloxybenzaldehyde derivatives against HL-60 cells.

A series of benzyloxybenzaldehyde derivatives were prepared and tested against the HL-60 cell line for anticancer activity. Preliminary structure-activity relationships were established. It was discovered that 2-(benzyloxy)benzaldehyde (17), 2-(benzyloxy)-4-methoxybenzaldehyde (26), 2-(benzyloxy)-5-methoxybenzaldehyde (27), 2-(benzyloxy)-5-chlorobenzaldehyde (28), 2-[(3-methoxybenzyl)oxy]benzaldehyde (29), 2-[(2-chlorobenzyl)oxy]benzaldehyde (30), and 2-[(4-chlorobenzyl)oxy]benzaldehyde (31) exhibited significant activity at 1-10 microM. Among them, compound 29 was the most potent one. The morphological assessment and DNA fragmentation analysis indicated that these compounds arrested cell cycle progression at G2/M phase and induced cell apoptosis. They resulted in the loss of mitochondrial membrane potential after 12h of treatment.

Investigation of the cellular mechanism of inhibition of formyl-methionyl-leucyl-phenylalanine-induced superoxide anion generation in rat neutrophils by 2-benzyloxybenzaldehyde.

The inhibition of formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide anion (O2(.-)) generation by 2-benzyloxybenzaldehyde (CCY1a) was investigated in rat neutrophils, and the underlying mechanism of this inhibition was assessed. CCY1a concentration-dependently inhibited O2(.-) generation (IC(50)=18.5+/-4.3 microM). In cell-free systems, CCY1a failed to alter O2(.-) generation during dihydroxyfumaric acid autoxidation, in phorbol 12-myristate 13-acetate (PMA)-activated neutrophil particulate NADPH oxidase preparations, or during arachidonic acid-induced NADPH oxidase activation. CCY1a increased cellular cyclic AMP (cAMP) levels in a time- and concentration-dependent manner, and this cAMP-elevating effect was inhibited by the adenylyl cyclase inhibitor 9-(tetrahydro-2'-furyl)adenine (SQ22536), adenosine deaminase (ADA), and the adenosine receptor antagonist 8-(p-sulfophenyl)theophylline. In neutrophils, inhibition of O2(.-) generation by CCY1a was partially reversed by the protein kinase A inhibitor (9R,10S,12S)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-l][1,6]benzodiazocine-10-carboxylic acid, hexyl ester (KT5720). CCY1a did not affect fMLP-induced p38 mitogen-activated protein kinase phosphorylation, but concentration-dependently attenuated the phosphorylation of extracellular signal-regulated kinase (ERK) and Akt (IC(50) about 31.3 and 19.4 microM, respectively). The plateau phase, but not the initial spike, of fMLP-induced [Ca2+](i) changes was inhibited by CCY1a in a concentration-dependent manner. CCY1a inhibition of Ca2+ entry, ERK, and Akt phosphorylation was not prevented by SQ22536 or ADA. fMLP-induced phospholipase D (PLD) activation was inhibited by CCY1a (IC(50)=13.9+/-2.0 microM). ADA and KT5720 did not prevent the inhibition of PLD activation by CCY1a. Collectively, these results indicate that the inhibition by CCY1a of fMLP-induced O2(.-) generation in rat neutrophils can probably be attributed to the increase in cAMP levels, and to the blockade of Ca2+ entry, suppression of Akt, and PLD activation via cAMP-independent mechanisms.

Inhibition of Ras-mediated cell proliferation by benzyloxybenzaldehyde.

Excessive proliferation of vascular smooth muscle cells (VSMC) in the intima is an important etiologic factor in vascular proliferative disorders such as atherosclerosis and restenosis after balloon angioplasty. Therefore, control of VSMC growth may be a suitable therapeutic intervention in vascular proliferative disorders. In the present work, we have studied the 2-benzyloxybenzaldehyde (CCY1a)-mediated antiproliferative effect and its mechanisms of action. CCY1a inhibited serum-induced VSMC proliferation in a concentration-dependent manner, as demonstrated using [(3)H]thymidine incorporation and MTT assays; the IC(50) values were calculated to be 7.0 x 10(-6) and 1.2 x 10(-5) M, respectively. Furthermore, it also significantly suppressed serum-induced progression of the cell cycle, as shown by flow cytometric analysis. CCY1a as well as PD98059 almost completely abolished serum-induced activation of p42/44 mitogen-activated protein kinase (MAPK), the downstream effectors of c-fos and c-jun mRNA expression and activator protein-1 (AP-1) DNA binding activity, suggesting the central roles of these signaling cascades. Interestingly, CCY1a also effectively blocked serum-induced Ikappa B-alpha phosphorylation, Ikappa B-alpha degradation and nuclear factor-kappa B (NF-kappa B) binding activity. Based on these observations, we examined the effect of CCY1a on serum-mediated Ras activity, an upstream regulator of the above signaling events. The data demonstrated a marked inhibition of Ras activation by CCY1a. We conclude that CCY1a blocks cell proliferation via inhibition of the upstream effector of Ras and downstream events, including p42/44 MAPK activation and c-fos and c-jun mRNA expression, as well as NF-kappa B and AP-1 DNA binding activities.