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1.
V KW Wong T Li B YK Law E DL Ma N C Yip F Michelangeli C KM Law M M Zhang K YC Lam P L Chan L Liu 《Cell death & disease》2013,4(7):e720
Autophagy is an important cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via the turnover of proteins and damaged organelles. However, persistent activation of autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to caspase-independent autophagic cell death. As such, inducing cell death through this autophagic mechanism could be an alternative approach to the treatment of cancers. Recently, we have identified a novel autophagic inducer, saikosaponin-d (Ssd), from a medicinal plant that induces autophagy in various types of cancer cells through the formation of autophagosomes as measured by GFP-LC3 puncta formation. By computational virtual docking analysis, biochemical assays and advanced live-cell imaging techniques, Ssd was shown to increase cytosolic calcium level via direct inhibition of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump, leading to autophagy induction through the activation of the Ca2+/calmodulin-dependent kinase kinase–AMP-activated protein kinase–mammalian target of rapamycin pathway. In addition, Ssd treatment causes the disruption of calcium homeostasis, which induces endoplasmic reticulum stress as well as the unfolded protein responses pathway. Ssd also proved to be a potent cytotoxic agent in apoptosis-defective or apoptosis-resistant mouse embryonic fibroblast cells, which either lack caspases 3, 7 or 8 or had the Bax-Bak double knockout. These results provide a detailed understanding of the mechanism of action of Ssd, as a novel autophagic inducer, which has the potential of being developed into an anti-cancer agent for targeting apoptosis-resistant cancer cells. 相似文献
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Park SK Kim DH Deung YK Kim HJ Yang EJ Lim SJ Ryang YS Jin D Lee KJ 《The Korean journal of parasitology》2004,42(4):201-203
A survey was conducted to determine the extent of intestinal parasite infection in Bat Dambang, Cambodia in March 2004. A total of 623 fecal specimens was collected from kindergarten and schoolchildren and examined using the formalin-ether sedimentation technique. The overall infection rate of intestinal parasites was 25.7% (boys, 26.2%; girls, 25.1%), and the infection rates of intestinal helminthes by species were as follows: Echinostoma sp. 4.8%, hookworm 3.4%, Hymenolepis nana 1.3%, and Rhabditis sp. 1.3%. The infection rates of intestinal protozoa were; Entamoeba coli 4.8%, Giardia lamblia 2.9%, Iodamoeba butschlii 1.4%, Entamoeba polecki 1.1%, and Entamoeba histolytica 0.8%. There were no egg positive cases of Ascaris lumbricoides or Trichuris trichiura. All children infected were treated with albendazole, praziquantel, or metronidazole according to parasite species. The results showed that intestinal parasites are highly endemic in Bat Dambang, Cambodia. 相似文献
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Katri Lindfors Keijo M Viiri Marjo Niittynen Taisto YK Heinonen Markku M?ki Heikki Kainulainen 《BMC genomics》2003,4(1):53
Background
We have previously set up an in vitro mesenchymal-epithelial cell co-culture model which mimics the intestinal crypt villus axis biology in terms of epithelial cell differentiation. In this model the fibroblast-induced epithelial cell differentiation from secretory crypt cells to absorptive enterocytes is mediated via transforming growth factor-β (TGF-β), the major inhibitory regulator of epithelial cell proliferation known to induce differentiation in intestinal epithelial cells. The aim of this study was to identify novel genes whose products would play a role in this TGF-β-induced differentiation. 相似文献5.
Hugo YK Lam Philip M Kim Janine Mok Raffi Tonikian Sachdev S Sidhu Benjamin E Turk Michael Snyder Mark B Gerstein 《BMC bioinformatics》2010,11(1):243
Background
Many protein interactions, especially those involved in signaling, involve short linear motifs consisting of 5-10 amino acid residues that interact with modular protein domains such as the SH3 binding domains and the kinase catalytic domains. One straightforward way of identifying these interactions is by scanning for matches to the motif against all the sequences in a target proteome. However, predicting domain targets by motif sequence alone without considering other genomic and structural information has been shown to be lacking in accuracy. 相似文献6.
Teng YK Verburg RJ Verpoort KN Diepenhorst GM Bajema IM van Tol MJ Jol-van der Zijde EC Toes RE Huizinga TW van Laar JM 《Arthritis research & therapy》2007,9(5):R106
In order to identify pathogenic correlates of refractory rheumatoid arthritis (RA), antibodies against anti-cyclic citrullinated
protein (ACPAs) were investigated in RA patients in whom the dysregulated immune system had been ablated by high-dose chemotherapy
(HDC) and autologous haematopoietic stem cell transplantation (HSCT). Six patients with refractory RA were extensively characterized
in terms of levels of total immunoglobulins, RA-specific autoantibodies (ACPAs and rheumatoid factor) and antibodies against
rubella, tetanus toxoid (TT) and phosphorylcholine before and after HDC plus HSCT. Additionally, the avidity of ACPAs was
measured before and after treatment and compared with the avidity of TT antibodies following repeated immunizations. Synovial
biopsies were obtained by arthroscopy before HDC plus HSCT, and analyzed by immunohistochemistry. In the three patients with
clinically long-lasting responses to HDC plus HSCT (median 423 days), significant reductions in ACPA-IgG levels after therapy
were observed (median level dropped from 215 to 34 arbitrary units/ml; P = 0.05). In contrast, stable ACPA-IgG levels were observed in three patients who relapsed shortly after HDC plus HSCT (median
of 67 days). Clinical responders had ACPA-IgG of lower avidity (r = 0.75; P = 0.08) and higher degree of inflammation histologically (r = 0.73; P = 0.09). Relapse (after 38 to 530 days) in all patients was preceded by rising levels of low avidity ACPA-IgG (after 30 to
388 days), in contrast to the stable titres of high avidity TT antibodies. In conclusion, humoral autoimmune responses were
differentially modulated by immunoablative therapy in patients with synovial inflammation and low avidity ACPA-IgG autoantibodies
as compared with patients with high levels of high avidity ACPA-IgG. The distinct clinical disease course after immunoablative
therapy based on levels and avidity of ACPA-IgG indicates that refractory RA is not a single disease entity. 相似文献
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Israel T Silva Ricardo ZN Vêncio Thiago YK Oliveira Greice A Molfetta Wilson A SilvaJr 《BMC bioinformatics》2010,11(1):161
Background
The post-genomic era has brought new challenges regarding the understanding of the organization and function of the human genome. Many of these challenges are centered on the meaning of differential gene regulation under distinct biological conditions and can be performed by analyzing the Multiple Differential Expression (MDE) of genes associated with normal and abnormal biological processes. Currently MDE analyses are limited to usual methods of differential expression initially designed for paired analysis. 相似文献8.
Background
Deacetylation of histones plays a fundamental role in gene silencing, and this is mediated by a corepressor complex containing Sin3 as an essential scaffold protein. In this report we examine the evolution of two proteins in this complex, the Sin3-associated proteins SAP30L and SAP30, by using an archive of protein sequences from 62 species. 相似文献9.
Han‐Shin Kim Eunji Cha So‐Young Ham Jeong‐Hoon Park SangJin Nam Hongmok Kwon Youngjoo Byun Hee‐Deung Park 《Biotechnology and bioengineering》2021,118(1):82-93
Bacterial biofilm formation causes serious problems in various fields of medical, clinical, and industrial settings. Antibiotics and biocide treatments are typical methods used to remove bacterial biofilms, but biofilms are difficult to remove effectively from surfaces due to their increased resistance. An alternative approach to treatment with antimicrobial agents is using biofilm inhibitors that regulate biofilm development without inhibiting bacterial growth. In the present study, we found that linoleic acid (LA), a plant unsaturated fatty acid, inhibits biofilm formation under static and continuous conditions without inhibiting the growth of Pseudomonas aeruginosa. LA also influenced the bacterial motility, extracellular polymeric substance production, and biofilm dispersion by decreasing the intracellular cyclic diguanylate concentration through increased phosphodiesterase activity. Furthermore, quantitative gene expression analysis demonstrated that LA induced the expression of genes associated with diffusible signaling factor‐mediated quorum sensing that can inhibit or induce the dispersion of P. aeruginosa biofilms. These results suggest that LA is functionally and structurally similar to a P. aeruginosa diffusible signaling factor (cis‐2‐decenoic acid) and, in turn, act as an agonist molecule in biofilm dispersion. 相似文献
10.
YK Onno Teng Gillian Wheater Vanessa E Hogan Philip Stocks EW Nivine Levarht Tom WJ Huizinga Rene EM Toes Jacob M van Laar 《Arthritis research & therapy》2012,14(2):R57