Chinese herbal medicine in the treatment of acute upper respiratory tract infection: a randomised, double blind, placebo-controlled clinical trial.

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Role of street patterns in zone-based traffic safety analysis

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Coiled-coil motif as a structural basis for the interaction of HTLV type 1 Tax with cellular cofactors

Human T lymphotropic virus type 1 (HTLV-1) Tax is a multifunctional protein centrally involved in transcriptional regulation, cell cycle control, and viral transformation. The regulatory functions of Tax are thought to be mediated through protein-protein interaction with cellular cofactors. Previously we have identified several novel binding partners for Tax, including human mitotic checkpoint protein MAD1 (TXBP181), G-protein pathway suppressor GPS2 (TXBP31), and IκB kinase regulatory subunit IKK-γ. Here we described two additional Tax partners, TXBP151 and TXBP121. A closer examination of the sequences of eight independent cellular Tax-binding proteins identified by us and others revealed that all of them share a single characteristic, a highly structured coiled-coil domain. We also noted that Tax and the Tax-binding coiled-coil proteins can homodimerize. Additionally, the same domain in Tax is responsible for interaction with different coiled-coil proteins. Taken together, our findings point to a particular coiled-coil structure as one of the Tax-recognition motifs. The interaction of Tax with a particular subgroup of cellular coiled-coil proteins represents one mechanism by which Tax dysregulates cell growth and proliferation.published_or_final_versio

Epigenetic inactivation of the miR-34a in hematological malignancies

miR-34a is a transcriptional target of p53 and implicated in carcinogenesis. We studied the role of miR-34a methylation in a panel of hematological malignancies including acute leukemia [acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)], chronic leukemia [chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML)], multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). The methylation status of miR-34a promoter was studied in 12 cell lines and 188 diagnostic samples by methylation-specific polymerase chain reaction. miR-34a promoter was unmethylated in normal controls but methylated in 75% lymphoma and 37% myeloma cell lines. Hypomethylating treatment led to re-expression of pri-miR-34a transcript in lymphoma cells with homozygous miR-34a methylation. In primary samples at diagnosis, miR-34a methylation was detected in 4% CLL, 5.5% MM samples and 18.8% of NHL at diagnosis but none of ALL, AML and CML (P = 0.011). In MM patients with paired samples, miR-34a methylation status remained unchanged at progression. Amongst lymphoid malignancies, miR-34a was preferentially methylated in NHL (P = 0.018), in particular natural killer (NK)/T-cell lymphoma. In conclusion, amongst hematological malignancies, miR-34a methylation is preferentially hypermethylated in NHL, in particular NK/T-cell lymphoma, in a tumor-specific manner, therefore the role of miR-34a in lymphomagenesis warrants further study. © The Author 2010. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]

Rho GTPase-activating protein deleted in liver cancer suppresses cell proliferation and invasion in hepatocellular carcinoma

Deleted in liver cancer (DLC1) is a candidate tumor suppressor gene recently isolated from human hepatocellular carcinoma. Structurally, DLC1 protein contains a conserved GTPase-activating protein for Rho family protein (RhoGAP) domain, which has been thought to regulate the activity of Rho family proteins. Previous studies indicated that DLC1 was frequently inactivated in cancer cells. In the present study, we aimed to characterize the tumor suppressor roles of DLC1 in hepatocellular carcinoma. We showed that DLC1 significantly inhibited cell proliferation, anchorage-independent growth, and in vivo tumorigenicity when stably expressed in hepatocellular carcinoma cells. Moreover, DLC1 expression greatly reduced the motility and invasiveness of hepatocellular carcinoma cells. With RhoGAP-deficient DLC1 mutant (DLC1-K714E), we showed that the RhoGAP activity was essential for DLC1-mediated tumor suppressor function. Furthermore, the 292- to 648-amino acid region and the steroidogenic acute regulatory related lipid transfer domain played an auxiliary role to RhoGAP and tumor suppressor function of DLC1. Taken together, our findings showed that DLC1 functions as a tumor suppressor in hepatocellular carcinoma and provide the first evidence to support the hypothesis that DLC1 suppresses cancer cell growth by negatively regulating the activity of Rho proteins. ©2005 American Association for Cancer Research.postprin

Significance of MAD2 expression in mitotic checkpoint control and cellular sensitivity in nasopharyngeal carcinoma cells

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Characterization of human and mouse peroxiredoxin IV: Evidence for inhibition by Prx-IV of epidermal growth factor- and p53-induced reactive oxygen species

The aim of this study was to identify and characterize human and mouse Prx-IV. We identified mouse peroxiredoxin IV (Prx-IV) by virtue of sequence homology to its human ortholog previously called AOE372. Mouse Prx-IV conserves an amino-terminal presequence coding for signal peptide. The amino acid sequences of mature mouse and human Prx-IV share 97.5% identity. Phylogenetic analysis demonstrates that Prx-IV is more closely related to Prx-I/-II/-III than to Prx-V/-VI. Previously, we mapped the mouse Prx-IV gene to chromosome X by analyzing two sets of multiloci genetic crosses. Here we performed further comparative analysis of mouse and human Prx-IV genomic loci. Consistent with the mouse results, human Prx-IV gene localized to chromosome Xp22.135-136, in close proximity to SAT and DXS7178. A bacterial artificial chromosome (BAC) clone containing the complete human Prx-IV locus was identified. The size of 7 exons and the sequences of the splice junctions were confirmed by PCR analysis. We conclude that mouse Prx-IV is abundantly expressed in many tissues. However, we could not detect Prx-IV in the conditioned media of NIH-3T3 and Jurkat cells. Mouse Prx-IV was specifically found in the nucleus-excluded region of cultured mouse cells. Intracellularly, overexpression of mouse Prx-IV prevented the production of reactive oxygen species induced by epidermal growth factor or p53. Taken together, mouse Prx-IV is likely a cytoplasmic or organellar peroxiredoxin involved in intracellular redox signaling.published_or_final_versio

The antioxidative effect of propofol on angiotesin II-induced apoptosis in neonatal rat cardiomyocytes

Theme: New Horizons on Cardiovascular DiseasesPosterOrganizer: International Academy of CardiologyPropofol (2,6-diisopropylphenol), an intravenous sedative Vhypnotic agent popular for sedation, has been found to be effective in protecting against pathological states characterized by an increase in basal rate of reactive oxygen species (ROS) production in hearts, but the cardioprotective mechanism is not well established. Angiotensin-II (Ang-II), an important neurohormonal factor during heart failure, can induce cardiomyocyte apoptosis which has an important role in the transition from compensatory cardiac remodeling to heart failure. In the present study, we evaluated the effects of propofol on Ang-II-mediated cardiomyocyte apoptosis. Cultured cardiomyocytes from neonatal rats were stimulated with Ang-II. Apoptosis was evaluated by measuring caspase 3 activity and by TdT-mediated dUTP nick-end labeling (TUNEL) method. It was found that incubation with Ang-II (0.1 micromolar) for 48 h increased cardiomyocyte apoptosis. Administration of propofol ...postprin

Micro-CT Imaging Reveals Mekk3 Heterozygosity Prevents Cerebral Cavernous Malformations in Ccm2-Deficient Mice.

Mutations in CCM1 (aka KRIT1), CCM2, or CCM3 (aka PDCD10) gene cause cerebral cavernous malformation in humans. Mouse models of CCM disease have been established by deleting Ccm genes in postnatal animals. These mouse models provide invaluable tools to investigate molecular mechanism and therapeutic approaches for CCM disease. However, the full value of these animal models is limited by the lack of an accurate and quantitative method to assess lesion burden and progression. In the present study we have established a refined and detailed contrast enhanced X-ray micro-CT method to measure CCM lesion burden in mouse brains. As this study utilized a voxel dimension of 9.5μm (leading to a minimum feature size of approximately 25μm), it is therefore sufficient to measure CCM lesion volume and number globally and accurately, and provide high-resolution 3-D mapping of CCM lesions in mouse brains. Using this method, we found loss of Ccm1 or Ccm2 in neonatal endothelium confers CCM lesions in the mouse hindbrain with similar total volume and number. This quantitative approach also demonstrated a rescue of CCM lesions with simultaneous deletion of one allele of Mekk3. This method would enhance the value of the established mouse models to study the molecular basis and potential therapies for CCM and other cerebrovascular diseases

Effects of helicobacter pylori treatment on incidence of gastric cancer in older individuals

Background & Aims: Although eradication of Helicobacter pylori infection reduces the risk of gastric cancer, few data are available on its effects in older subjects. We compared the age-specific risk of gastric cancer in a large cohort of subjects who received H pylori eradication therapy vs a matched general population. / Methods: We searched the Hospital Authority database of Hong Kong to identify individuals with H pylori infection who had received a course of clarithromycin-containing eradication therapy from January 2003 through December 2012. We compared the gastric cancer incidence in this cohort with the expected incidence for the local general population by retrieving the gastric cancer incidence of the age- and sex-matched population from 2003 through 2014 (the latest available year) from the Hong Kong Cancer Registry. The primary outcome was the incidence of gastric cancer development in the cohort treated for H pylori infection vs the expected number of gastric cancer cases in the general population. Analyses were conducted by a priori age groups of less than 40 years, 40–59 years, and 60 years or older. / Results: Among 73,237 subjects infected with H pylori who received eradication therapy, 200 (0.27%) developed gastric cancer during a median follow-up time of 7.6 years. Compared with the matched general population, the gastric cancer risk was significantly lower in subjects 60 years or older who had received H pylori treatment (standardized incidence ratio [SIR], 0.82; 95% confidence interval [CI], 0.69–0.97; P = .02) but not in younger groups. When data were stratified based on time from H pylori treatment (less than 5 years, 5–9 years, and 10 or more years), the risk of gastric cancer was significantly lower than the general population 10 or more years after eradication in the group 40–59 years old (SIR 0.32; 95% CI, 0.08–0.88; P = .04) and the group 60 years or older (SIR, 0.42; 95% CI, 0.42–0.84; P = .02) than the other age groups. / Conclusions: In an analysis of data from a public hospital database on Hong Kong, we associated treatment of H pylori infection with a lower risk of gastric cancer, particularly in older subjects, 10 or more years after treatment