Albumin fibrillization induces apoptosis via integrin/FAK/Akt pathway

[[abstract]]Background: Numerous proteins can be converted to amyloid-like fibrils to increase cytotoxicity and induce apoptosis, but the methods generally require a high concentration of protein, vigorous shaking, or fibril seed. As well, the detailed mechanism of the cytotoxic effects is not well characterized. In this study, we have developed a novel process to convert native proteins into the fibrillar form. We used globular bovine serum albumin (BSA) as a model protein to verify the properties of the fibrillar protein, investigated its cellular effects and studied the signaling cascade induced by the fibrillar protein. Results: We induced BSA, a non-cytotoxic globular protein, to become fibril by a novel process involving Superdex-200 column chromatography in the presence of anionic or zwittergenic detergent(s). The column pore size was more important than column matrix composite in fibril formation. The fibrillar BSA induced apoptosis in BHK-21 cell as well as breast cancer cell line T47D. Pre-treating cells with anti-integrin antibodies blocked the apoptotic effect. Fibrillar BSA, but not globular BSA, bound to integrin, dephosphorylated focal adhesion kinase (FAK), Akt and glycogen synthase kinase-3β (GSK-3β). Conclusion: We report on a novel process for converting globular proteins into fibrillar form to cause apoptosis by modulating the integrin/FAK/Akt/GSK-3β/caspase-3 signaling pathway. Our findings may be useful for understanding the pathogenesis of amyloid-like fibrils and applicable for the development of better therapeutic agents that target the underlying mechanism(s) of the etiologic agents. ? 2009 Huang et al; licensee BioMed Central Ltd

Apoptotic Cell Death and Inhibition of Wnt/β-Catenin Signaling Pathway in Human Colon Cancer Cells by an Active Fraction (HS7) from Taiwanofungus camphoratus

Aberrant activation of Wnt/β-catenin signaling plays an important role in the development of colon cancer. HS7 is an active fraction extracted from Taiwanofungus camphoratus, which had been widely used as complementary medicine for Taiwan cancer patients in the past decades. In this study, we demonstrated the effects of HS7 on the growth inhibition, apoptosis induction, and Wnt/β-catenin signaling suppression in human colon cancer cells. HS7 significantly inhibited proliferation of HT29, HCT116, and SW480 colon cancer cells in a dose- and time-dependent manner. The apoptosis induction was evidenced by DNA fragmentation and subG1 accumulation, which was associated with increased Bax/Bcl-2 ratio, activation of caspase-3 and cleavage of PARP. By using Tcf-dependent luciferase activity assay, HS7 was found to inhibit the β-catenin/Tcf transcriptional activities. In addition, HS7 strongly suppressed the binding of Tcf complexes to its DNA-binding site shown in electrophoretic mobility shift assay. This inhibition was further confirmed by the decreased protein levels of Tcf-4 and β-catenin. The β-catenin/Tcf downstream target genes, such as survivin, c-myc, cyclin D1, MMP7, and MT1-MMP involved in apoptosis, invasion, and angiogenesis were also diminished as well. These results indicate that Taiwanofungus camphoratus may provide a benefit as integrative medicine for the treatment of colon cancer

Induction of protective immunity in swine by recombinant bamboo mosaic virus expressing foot-and-mouth disease virus epitopes

<p>Abstract</p> <p>Background</p> <p>Plant viruses can be employed as versatile vectors for the production of vaccines by expressing immunogenic epitopes on the surface of chimeric viral particles. Although several viruses, including tobacco mosaic virus, potato virus X and cowpea mosaic virus, have been developed as vectors, we aimed to develop a new viral vaccine delivery system, a bamboo mosaic virus (BaMV), that would carry larger transgene loads, and generate better immunity in the target animals with fewer adverse environmental effects.</p> <p>Methods</p> <p>We engineered the BaMV as a vaccine vector expressing the antigenic epitope(s) of the capsid protein VP1 of foot-and-mouth disease virus (FMDV). The recombinant BaMV plasmid (pBVP1) was constructed by replacing DNA encoding the 35 N-terminal amino acid residues of the BaMV coat protein with that encoding 37 amino acid residues (T¹²⁸-N¹⁶⁴) of FMDV VP1.</p> <p>Results</p> <p>The pBVP1 was able to infect host plants and to generate a chimeric virion BVP1 expressing VP1 epitopes in its coat protein. Inoculation of swine with BVP1 virions resulted in the production of anti-FMDV neutralizing antibodies. Real-time PCR analysis of peripheral blood mononuclear cells from the BVP1-immunized swine revealed that they produced VP1-specific IFN-γ. Furthermore, all BVP1-immunized swine were protected against FMDV challenge.</p> <p>Conclusion</p> <p>Chimeric BaMV virions that express partial sequence of FMDV VP1 can effectively induce not only humoral and cell-mediated immune responses but also full protection against FMDV in target animals. This BaMV-based vector technology may be applied to other vaccines that require correct expression of antigens on chimeric viral particles.</p

Estimation of life expectancy and healthcare cost in rheumatoid arthritis patients with and without depression: a population-based retrospective cohort study

PurposeThis study aimed to estimate the lifetime healthcare costs and loss of life expectancy (loss-of-LE) among patients with incident rheumatoid arthritis (RA) with and without depression.MethodsThis 18 years longitudinal cohort study used data from Taiwan’s National Health Insurance Research Database. In total, 43,311 patients with RA were included. Among them, 1,663 patients had depressive disorders in the year preceding the RA diagnosis. The survival function for patients with RA with or without depression was estimated and extrapolated over a lifetime using the rolling extrapolation algorithm. The loss-of-LE was calculated by comparing the sex, age, and calendar year-matched referents from vital statistics. The average monthly cost was calculated as the sum of the monthly costs for all patients divided by the number of surviving patients. Lifetime healthcare costs were estimated by multiplying the monthly average cost by the monthly survival probability.ResultsThe loss-of-LE for RA patients with and without depression was 5.60 years and 4.76 years, respectively. The lifetime costs of RA patients with and without depression were USD$90,346 and USD$ 92,239, respectively. However, the annual healthcare costs were USD$4,123 for RA patients with depression and USD$ 3,812 for RA patients without depression. Regardless of sex or age, RA patients with depression had higher annual healthcare costs than those without depression.ConclusionPatients with RA and depression have a high loss-of-LE and high annual healthcare costs. Whether treating depression prolongs life expectancy and reduces healthcare costs warrants further investigation

HPV infection and p53 inactivation in pterygium

PurposeOur recent report indicated that tumor suppressor gene (p53) mutations and protein aberrant expression were detected in pterygium. Inactivation of p53 by Human papillomavirus (HPV) 16/18 E6 plays a crucial role in cervical tumorigenesis. In this study, we further speculate that p53 inactivation may be linked with HPV infection in pterygium pathogenesis. To investigate the involvement of HPV 16/18 E6 in p53 inactivation in pterygium, the association between HPV 16 or HPV 18 infection, the HPV E6 oncoprotein, and p53 protein expression was analyzed in this study.MethodsHPV 16/18 infection was detected by nested-polymerase chain reaction (nested-PCR), the p53 mutation was detected by direct sequencing, and the p53 and the HPV 16/18 E6 proteins were studied using immunohistochemistry on 129 pterygial specimens and 20 normal conjunctivas.ResultsThe HPV 16/18 was detected in 24% of the pterygium tissues (31 of 129) but not in the normal conjunctiva, and the HPV16/18 E6 oncoprotein was detected in 48.3% of HPV 16/18 DNA-positive pterygium tissues (15 of 31). In addition, p53 protein negative expression in pterygium was correlated with HPV16/18 E6 oncoprotein expression but not with a p53 mutation.ConclusionsHPV 16/18 E6 contributes to HPV-mediated pterygium pathogenesis as it is partly involved in p53 inactivation and is expressed in HPV DNA-positive pterygium

Interaction between Thalamus and Hippocampus in Termination of Amygdala-Kindled Seizures in Mice

The thalamus and hippocampus have been found both involved in the initiation, propagation, and termination of temporal lobe epilepsy. However, the interaction of these regions during seizures is not clear. The present study is to explore whether some regular patterns exist in their interaction during the termination of seizures. Multichannel in vivo recording techniques were used to record the neural activities from the cornu ammonis 1 (CA1) of hippocampus and mediodorsal thalamus (MDT) in mice. The mice were kindled by electrically stimulating basolateral amygdala neurons, and Racine’s rank standard was employed to classify the stage of behavioral responses (stage 1~5). The coupling index and directionality index were used to investigate the synchronization and information flow direction between CA1 and MDT. Two main results were found in this study. (1) High levels of synchronization between the thalamus and hippocampus were observed before the termination of seizures at stage 4~5 but after the termination of seizures at stage 1~2. (2) In the end of seizures at stage 4~5, the information tended to flow from MDT to CA1. Those results indicate that the synchronization and information flow direction between the thalamus and the hippocampus may participate in the termination of seizures

Lasing on nonlinear localized waves in curved geometry

The use of geometrical constraints opens many new perspectives in photonics and in fundamental studies of nonlinear waves. By implementing surface structures in vertical cavity surface emitting lasers as manifolds for curved space, we experimentally study the impacts of geometrical constraints on nonlinear wave localization. We observe localized waves pinned to the maximal curvature in an elliptical-ring, and confirm the reduction in the localization length of waves by measuring near and far field patterns, as well as the corresponding dispersion relation. Theoretically, analyses based on a dissipative model with a parabola curve give good agreement remarkably to experimental measurement on the transition from delocalized to localized waves. The introduction of curved geometry allows to control and design lasing modes in the nonlinear regime.Comment: 6 pages, 6 figure