Common variants in FLNB/CRTAP, not ARHGEF3 at 3p, are associated with Osteoporosis in southern Chinese women

We performed an association study of five candidate genes within chromosome 3p14-25 in 1,080 Chinese female subjects. Polymorphisms in FLNB/CRTAP are associated with bone mineral density (BMD) in Chinese. Introduction: Chromosomal region 3p14-25 has shown strong evidence of linkage to BMD in genome-wide linkage scans. The variants responsible for this linkage signal, nonetheless, remain obscure. Methods: Thirty SNPs in five positional and functional candidate genes within 3p14-25 (PPARG, CRTAP, TDGF1, PTHR1, and FLNB) and rs7646054 in the ARHGEF3 gene were genotyped in a case-control cohort of 1,080 Chinese females. Allelic and haplotypic association were tested using logistic regression analysis implemented in PLINK software. Potential transcription factor binding sites were predicted with Mat Inspector. Results: Multiple SNPs and haplotypes in FLNB were significantly associated with BMDs, with the strongest association between lumbar spine BMD and rs9828717 (p=0.005). SNP rs7623768 and the haplotype G-C of rs4076086-rs7623768 in CRTAP were associated with femoral neck BMD (p=0.009 and p=0.003, respectively). PTHR1 showed haplotypic associations with lumbar spine and femoral neck BMD (p=0.02 and p=0.044, respectively). Nevertheless, the association between rs7646054 in ARHGEF3 and BMD observed in Caucasians was not replicated in our samples. Comparative genomics analysis indicated that rs9828717 is located within a highly conserved region. The minor T allele at rs9828717 may lead to loss of binding site for nuclear factor of activated T cells which binds and triggers the transcriptional program of osteoblasts. Conclusions: Our data suggest that variants in FLNB and CRTAP at 3p are involved in BMD regulation in southern Chinese. © International Osteoporosis Foundation and National Osteoporosis Foundation 2009.published_or_final_versionSpringer Open Choice, 01 Dec 201

Desensitization of T lymphocyte function by CXCR3 ligands in human hepatocellular carcinoma

Aim: Despite the presence of lymphocyte infiltration, human hepatocellular carcinoma (HCC) is typically a rapidly progressive disease. The mechanism of regulation of lymphocyte migration is poorly understood. In this study, we investigated various factors regulating T cell migration in HCC patients. We examined serum CXC chemokine levels in HCC patients and demonstrated the production of CXC chemokines by HCC cell lines. We determined the effect of both HCC patient serum and tumor cell conditioned supernatant upon lymphocyte expression of chemokine receptor CXCR3 as well as lymphocyte migration. Lastly, we examined the chemotactic responses of lymphocytes derived from HCC patients. Methods: The serum chemokines IP-10 (CXCL10) and Mig (CXCL9) levels were measured by cytometric bead array (CBA) and the tumor tissue IP-10 concentration was measured by ELISA. The surface expression of CXCR3 on lymphocytes was determined by flow cytometry. The migratory function of lymphocytes to the corresponding chemokines was assessed using an in vitro chemotactic assay. Phosphorylation of extracellular signal-regulated kinase (ERK) was determined by Western blot analysis. Results: Increased levels of IP-10 and Mig were detected in HCC patient serum and culture supernatants of HCC cell lines. The IP-10 concentration in the tumor was significantly higher than that in the non-involved adjacent liver tissues. HCC cell lines secreted functional chemokines that induced a CXCR3-specific chemotactic response of lymphocytes. Furthermore, tumor-cell-derived chemokines induced initial rapid phosphorylation of lymphocyte ERK followed by later inhibition of ERK phosphorylation. The culture of normal lymphocytes with HCC cell line supernatants or medium containing serum from HCC patients resulted in a significant reduction in the proportion of lymphocytes exhibiting surface expression of CXCR3. The reduction in T cell expression of CXCR3 resulted in reduced migration toward the ligand IP-10, and both CD4 + and CD8 + T cells from HCC patients exhibited diminished chemotactic responses to IP-10 in vitro compared to T cells from healthy control subjects. Conclusion: This study demonstrates functional desensitization of the chemokine receptor CXCR3 in lymphocytes from HCC patients by CXCR3 ligands secreted by tumor cells. This may cause lymphocyte dysfunction and subsequently impaired immune defense against the tumor. © 2005 The WJG Press and Elsevier Inc. All rights reserved.published_or_final_versio

Use of functional MRI to evaluate correlation between acupoints and brain cortex activites: comparison between conventional and electrical acupuncture

The use of acupuncture therapy in various functional disorders goes back several thousand years in China. Recendy, acupuncture becomes a 'hot' topic in the functional Magnetic Resonance (MR) imaging research studies [1-4]. A majority of these research projects is to study die correlation between the acupuncture points (acupoints) and die corresponding brain cortices, either by conventional acupuncture, electro-acupuncture or laser acupuncture. Cho et al reported mat by stimulating die vision-related acupoints (BL60, BL65, BL66, BL67) at the lateral side of die foot, neural response (i.e. high signal) was obtained at die visual cortex [1]. In this study, we verified Cho et al acupoints using conventional acupuncture and electro-acupuncture.published_or_final_versio

Hepatitis B Virus Core Promoter Double Mutations (A1762T, G1764A) Are Associated with Lower Levels of Serum Dihydrolipoyl Dehydrogenase

Published by S. Karger AG, BaselObjectives: The aim of this study was to identify serum proteins with differential concentrations between hepatocellular carcinoma (HCC) patients and HBsAg asymptomatic carriers among individuals infected with hepatitis B virus (HBV) with basal core promoter (BCP) double mutations (A1762T, G1764A). Methods: iTRAQ and liquid chromatography-tandem mass spectrometry were used to identify differentially expressed protein, and an ELISA test was used for the validation test. Results: The total number of proteins identified was 1,125, of which 239 showed statistically significant differences in their expression. The relative concentrations of serum dihydrolipoyl dehydrogenase (DLD), which showed the most significant correlation with liver diseases and infection, were significantly lower in HCC patients than asymptomatic HBsAg carriers and individuals negative for HBsAg. However, only the difference between HCC patients with BCP double mutations and HBsAg-negative individuals could be confirmed by ELISA. Meanwhile, we found that the concentrations of serum DLD in those infected with HBV with BCP double mutations were significantly lower than in individuals with the wild-type BCP. However, the difference in the concentrations of serum DLD between individuals with wild-type BCP and those negative for HBsAg was not significant. Conclusions: HBV with BCP double mutations are associated with lower concentrations of serum DLD

Synchronous bursts on scale-free neuronal networks with attractive and repulsive coupling

This paper investigates the dependence of synchronization transitions of bursting oscillations on the information transmission delay over scale-free neuronal networks with attractive and repulsive coupling. It is shown that for both types of coupling, the delay always plays a subtle role in either promoting or impairing synchronization. In particular, depending on the inherent oscillation period of individual neurons, regions of irregular and regular propagating excitatory fronts appear intermittently as the delay increases. These delay-induced synchronization transitions are manifested as well-expressed minima in the measure for spatiotemporal synchrony. For attractive coupling, the minima appear at every integer multiple of the average oscillation period, while for the repulsive coupling, they appear at every odd multiple of the half of the average oscillation period. The obtained results are robust to the variations of the dynamics of individual neurons, the system size, and the neuronal firing type. Hence, they can be used to characterize attractively or repulsively coupled scale-free neuronal networks with delays.Comment: 15 pages, 9 figures; accepted for publication in PLoS ONE [related work available at http://arxiv.org/abs/0907.4961 and http://www.matjazperc.com/

Comparative study on microstructure and surface properties of keratin- and lignocellulosic-based activated carbons

© 2015 Elsevier B.V. All rights reserved. The paper probed the preparation of activated carbon by potassium silicate (K2SiO3) activation from keratin waste (cowhair waste, CW) and lignocellulosic materials (Cyperus alternifolius, CA) and the comparisons of physicochemical properties of the resulting carbons. These impregnation conditions were as follows: one impregnated at room temperature for 12 h then dipped at high temperature for 30 min; the other was only impregnated at room temperature for 12 h, producing four activated carbons CWAC-1, CWAC-2, CAAC-1, and CAAC-2. The influence of activation time, K2SiO3/precursor weight ratio, and the pre-process on properties of activated carbons was discussed. The CWAC-1 produced at 700°C with the K2SiO3/precursor weight ratio of 2:1 possessed the Brunauer-Emmet-Teller (BET) surface area of 1965 m2/g and total pore volume of 1.345 cm3/g, while CAAC-1 prepared at the same conditions attained the BET surface area of 1710 m2/g and total pore volume of 0.949 cm3/g. The surface area and total pore volume of CAAC increased with the impregnation ratio. Moreover, CWAC-1, CWAC-2, CAAC-1, and CAAC-2 exhibited high portion of micropores, illustrating the role of K2SiO3. The analysis with a Fourier transform infrared spectrometer indicates that CWAC has more functional groups than CAAC, as well as CWAC-1 and CWAC-2 which possess similar functional groups

Bold signal changes of the visual cortex on stimulation of the vision-related acupoints

We verified Cho and his colleagues' acupoints using conventional acupuncture and electro-acupuncture. Acupuncture was performed with two different techniques - conventional and electro-acupuncture. Functional MR imaging (fMRI) was performed using a 1.5 T MR scanner with standard scan parameters in 13 healthy volunteers. The 30-second activation period was alternated by 30-second rest period. First, the fMRI was performed with visual activation using light-emitting diodes (LED) flashing with a frequency of 8 Hz. The fMRI was then repeated with conventional acupuncture and electro-acupuncture at the following acupoints (BL60, BL 65, BL 66 and BL 67) located in the lateral aspect of the foot. The activated pixels in the visual cortex created by visual activation correlate well with those created by both conventional acupuncture and electro-acupuncture Fig. 1. The results obtained by conventional acupuncture stimulation have relatively more neural responses due to other types of stimulation rather than visual activation. The neural responses obtained by electro-acupuncture at 2 Hz was found to be stronger than those obtained by electro-acupuncture at 64 Hz. The greatest difficulty encountered by the researchers is that only 25 to 30% of the subjects undergoing acupuncture renders expected neural response. Supported by The Hong Kong Jockey Club Charities Trust and The Hong Kong University Foundation.published_or_final_versio

Physiology and cell biology of acupuncture observed in calcium signaling activated by acoustic shear wave

This article presents a novel model of acupuncture physiology based on cellular calcium activation by an acoustic shear wave (ASW) generated by the mechanical movement of the needle. An acupuncture needle was driven by a piezoelectric transducer at 100 Hz or below, and the ASW in human calf was imaged by magnetic resonance elastography. At the cell level, the ASW activated intracellular Ca 2+ transients and oscillations in fibroblasts and endothelial, ventricular myocytes and neuronal PC-12 cells along with frequency-amplitude tuning and memory capabilities. Monitoring in vivo mammalian experiments with ASW, enhancement of endorphin in blood plasma and blocking by Gd 3+ were observed; and increased Ca 2+ fluorescence in mouse hind leg muscle was imaged by two-photon microscopy. In contrast with traditional acupuncture models, the signal source is derived from the total acoustic energy. ASW signaling makes use of the anisotropy of elasticity of tissues as its waveguides for transmission and that cell activation is not based on the nervous system. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

EM23, a natural sesquiterpene lactone, targets thioredoxin reductase to activate JNK and cell death pathways in human cervical cancer cells

Sesquiterpene lactones (SLs) are the active constituents of a variety of medicinal plants and found to have potential anticancer activities. However, the intracellular molecular targets of SLs and the underlying molecular mechanisms have not been well elucidated. In this study, we observed that EM23, a natural SL, exhibited anti-cancer activity in human cervical cancer cell lines by inducing apoptosis as indicated by caspase 3 activation, XIAP downregulation and mitochondrial dysfunction. Mechanistic studies indicated that EM23-induced apoptosis was mediated by reactive oxygen species (ROS) and the knockdown of thioredoxin (Trx) or thioredoxin reductase (TrxR) resulted in a reduction in apoptosis. EM23 attenuated TrxR activity by alkylation of C-terminal redox-active site Sec498 of TrxR and inhibited the expression levels of Trx/TrxR to facilitate ROS accumulation. Furthermore, inhibition of Trx/TrxR system resulted in the dissociation of ASK1 from Trx and the downstream activation of JNK. Pretreatment with ASK1/JNK inhibitors partially rescued cells from EM23-induced apoptosis. Additionally, EM23 inhibited Akt/mTOR pathway and induced autophagy, which was observed to be proapoptotic and mediated by ROS. Together, these results reveal a potential molecular mechanism for the apoptotic induction observed with SL compound EM23, and emphasize its putative role as a therapeutic agent for human cervical cancer.published_or_final_versio