Ganoderma lucidum polysaccharides in human monocytic leukemia cells: from gene expression to network construction

<p>Abstract</p> <p>Background</p> <p><it>Ganoderma lucidum </it>has been widely used as a herbal medicine for promoting health and longevity in China and other Asian countries. Polysaccharide extracts from <it>Ganoderma lucidum </it>have been reported to exhibit immuno-modulating and anti-tumor activities. In previous studies, F3, the active component of the polysaccharide extract, was found to activate various cytokines such as IL-1, IL-6, IL-12, and TNF-<it>α</it>. This gave rise to our investigation on how F3 stimulates immuno-modulating or anti-tumor effects in human leukemia THP-1 cells.</p> <p>Results</p> <p>Here, we integrated time-course DNA microarray analysis, quantitative PCR assays, and bioinformatics methods to study the F3-induced effects in THP-1 cells. Significantly disturbed pathways induced by F3 were identified with statistical analysis on microarray data. The apoptosis induction through the DR3 and DR4/5 death receptors was found to be one of the most significant pathways and play a key role in THP-1 cells after F3 treatment. Based on time-course gene expression measurements of the identified pathway, we reconstructed a plausible regulatory network of the involved genes using reverse-engineering computational approach.</p> <p>Conclusion</p> <p>Our results showed that F3 may induce death receptor ligands to initiate signaling via receptor oligomerization, recruitment of specialized adaptor proteins and activation of caspase cascades.</p

Biphasic Effect of Curcumin on Morphine Tolerance: A Preliminary Evidence from Cytokine/Chemokine Protein Array Analysis

The aim of this study was to evaluate the effect of curcumin on morphine tolerance and the corresponding cytokine/chemokine changes. Male ICR mice were made tolerant to morphine by daily subcutaneous injection for 7 days. Intraperitoneal injections of vehicle, low-dose or high-dose curcumin were administered 15 min after morphine injection, either acutely or chronically for 7 days to test the effect of curcumin on morphine-induced antinociception and development of morphine tolerance. On day 8, cumulative dose-response curves were generated and the 50% of maximal analgesic dose values were calculated and compared among groups. Corresponding set of mice were used for analyzing the cytokine responses by antibody-based cytokine protein array. Acute, high-dose curcumin enhanced morphine-induced antinociception. While morphine tolerance was attenuated by administration of low-dose curcumin following morphine injections for 7 days, it was aggravated by chronic high-dose curcumin following morphine injection, suggesting a biphasic effect of curcumin on morphine-induced tolerance. Of the 96 cytokine/chemokines analyzed by mouse cytokine protein array, 14 cytokines exhibited significant changes after the different 7-day treatments. Mechanisms for the modulatory effects of low-dose and high-dose curcumin on morphine tolerance were discussed. Even though curcumin itself is a neuroprotectant and low doses of the compound serve to attenuate morphine tolerance, high-doses of curcumin might cause neurotoxicity and aggravate morphine tolerance by inhibiting the expression of antiapoptotic cytokines and neuroprotective factors. Our results indicate that the effect of curcumin on morphine tolerance may be biphasic, and therefore curcumin should be used cautiously

Significantly Higher Percentage of Circulating CD27high Plasma Cells in Systemic Lupus Erythematosus Patients with Infection than with Disease Flare-Up

∙The authors have no financial conflicts of interest. Purpose: To distinguish lupus flare-up from infection in systemic lupus erythematosus (SLE), we analyze the expression of circulating CD27 high plasma cells in SLE patients with and without infection, in comparison to non-SLE patients with infection. Materials and Methods: The percentage of circulating CD27 high plasma cells was measured by flow cytometry in the following four groups: 36 SLE patients without infection, 23 SLE patients with infection, eight non-SLE patients with infection, and 26 healthy controls. Results: The frequency of CD27 high plasma cells had a correlation with the SLE disease activity index (SLEDAI) (r = 0.866, p &lt; 0.05), level of anti-dsDNA (r = 0.886, p &lt; 0.05), C3 (r =- 0.392, p &lt; 0.05), and C4 (r =- 0.337, p &lt; 0.05) in SLE patients without infection, but there was no correlation with disease activity in SLE patients with infection. Among three groups in particular-SLE without infection, SLE with infection, and non-SLE with infection-the percentages of CD27 high plasma cells were elevated. The percentage o

Macropinocytosis: Possible Mechanisms of Cellular Entry of Arginine-Rich Intracellular Delivery Peptides

Endocytosis, which plays a key role in many different species, is the process that cells take up extracellular materials through plasma membranes. Protein transduction domains (PTDs), also called cell-penetrating peptides (CPPs), are small peptides and contain a large amount of basic amino acids. Several PTDs, including arginine-rich intracellular delivery (AID) peptides, were found to be responsible for cellular uptake of macromolecules. In our previous studies, AID peptides have been proven to either covalently transport proteins or noncovalently internalize proteins, DNAs or RNAs into animal or plant cells. The mechanisms by which PTD enter cells are still in vigorous debate. Our studies indicated that the possible mechanisms of AID peptide-mediated cellular entry might involve a combination of multiple internalization pathways, including at least macropinocytosis. Furthermore, our recent reports demonstrated for the first time that AID peptides could rapidly and efficiently deliver proteins into animal and plant cells in both covalent and noncovalent protein transductions (CNPT) synchronously. Therefore, investigations of cellular uptake mediated by AID peptides facilitate our understanding of endocytosis in more details and reveal nonclassically endocytic pathways

Sialic-Acid-Related Enzymes of B Cells and Monocytes as Novel Markers to Discriminate Improvement Categories and to Fulfill Two Remission Definitions in Rheumatoid Arthritis

The enzymes α-2,6-sialyltransferase 1 (ST6Gal1), neuraminidase 1 (Neu1), α-2,3-sialyltransferase 1 (ST3Gal1), and neuraminidase 3 (Neu3) are known to affect immune cell function. However, it is not known whether the levels of these enzymes relate to remission definitions or differentiate American College of Rheumatology (ACR), European League Against Rheumatism (EULAR), and Simplified Disease Activity Index (SDAI) responses in patients with rheumatoid arthritis (RA). We measured the ST6Gal1, Neu1, ST3Gal1, and Neu3 levels of B cells and monocytes in RA patients and correlated the cells’ enzyme levels/ratios with the improvement in the ACR, EULAR and SDAI responses and with the two remission definitions. The difference in the B-cell Neu1 levels differed between the ACR 70% improvement and non-improvement groups (p = 0.043), between the EULAR good major response (improvement) and non-good response groups (p = 0.014), and also between the SDAI 50% or 70% improvement and non-improvement groups (p = 0.001 and 0.018, respectively). The same held true when the RA patients were classified by positive rheumatoid factor or the use of biologics. The B-cell Neu1 levels significantly indicated 2005 modified American Rheumatism Association and 2011 ACR/EULAR remission definitions (area under the curve (AUC) = 0.674 with p = 0.001, and AUC = 0.682 with p < 0.001, respectively) in contrast to the CRP and ESR (all AUCs < 0.420). We suggest that B-cell Neu1 is superior for discriminating ACR, EULAR, and SDAI improvement and is good for predicting two kinds of remission definitions

A specific tumor-targeting magnetofluorescent nanoprobe for dual-modality molecular imaging

[[abstract]]Poly(acrylic acid) was decorated onto Fe3O4 resulting in a highly water-soluble superparamagnetic iron oxide. The Poly(acrylic acid) iron oxide (PAAIO) complexes possess specific magnetic properties in the presence of an external magnetic field and are attractive contrast agents for magnetic resonance imaging (MRI). The free carboxylic groups of PAAIO exposed on the surface allow for covalent attachment of a fluorescent dye, Rhodamine 123 (Rh123) to form PAAIO-Rh123, which permits applications in fluorescence imaging. PAAIO-Rh123 is therefore a dual-modality molecular probe. In order to endow specific properties to compounds that target cancer cells and to prevent recognition by the reticuloendothelial system (RES), folic acid-linked poly(ethylene glycol) (FA-PEG) was further conjugated onto PAAIO-Rh123. The amounts of Rh123 and FA-PEG on the modified iron oxides were quantitatively determined by elemental analysis. The iron content was determined by inductively coupled plasma-optical emission spectrometer (ICP-OES). The particle diameters were characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). Superparamagnetism was confirmed by the superconducting quantum interference device (SQUID) magnetometer. The cellular internalization efficacy of the modified iron oxides was realized in folate-overexpressed FR(t) and folate-deficient FR(_) KB cells by flow cytometry and confocal laser scanning microscopy (CLSM). The quantitative amount of iron internalized into different harvested KB cells was measured by ICP-OES. The T2-weighted MR images were tested in FR(t) KB cells

Association of Reduced Tumor Necrosis Factor Alpha, Gamma Interferon, and Interleukin-1β (IL-1β) but Increased IL-10 Expression with Improved Chest Radiography in Patients with Pulmonary Tuberculosis▿

Mycobacterium tuberculosis infection is a major world health issue. The early identification of patients at risk for a poor response to anti-M. tuberculosis therapy would help elucidate the key players in the anti-M. tuberculosis response. The objective of the present study was to correlate the modulation of cytokine expression (interleukin-1 [IL-1], IL-6, IL-8, IL-10, IL-12, gamma interferon [IFN-γ], interferon-inducible protein [IP-10], and monocyte chemotactic protein 1 [MCP-1]) with the clinical response to 2 months of intensive therapy. From January to December 2007, 40 M. tuberculosis-infected patients and 40 healthy patients were recruited. After exclusion for diabetes, 32 patients and 36 controls were analyzed. The clinical responses of the M. tuberculosis-infected patients on the basis of the findings of chest radiography were compared to their plasma cytokine levels measured before and after 2 months of intensive anti-M. tuberculosis therapy and 6 months of therapy with human cytokine antibody arrays. Chest radiographs of 20 of 32 M. tuberculosis-infected patients showed improvement after 2 months of intensive therapy (early responders), while the M. tuberculosis infections in 12 of 32 of the patients resolved after a further 4 months (late responders). The levels of expression of TNF-α, MCP-1, IFN-γ, and IL-1β were decreased; and the level of IL-10 increased in early responders. After adjustment for age, gender, and the result of sputum culture for M. tuberculosis, significant differences in the levels of MCP-1 and IP-10 expression were observed between the early and the late responders after 2 months of intensive anti-M. tuberculosis therapy. Due to the interpatient variability in IP-10 levels, intrapatient monitoring of IP-10 levels may provide more insight into the M. tuberculosis responder status than comparison between patients. Plasma MCP-1 levels were normalized in patients who had resolved their M. tuberculosis infections. Further studies to evaluate the association of the modulation in MCP-1 levels with early and late responses are warranted

Complete Genome Sequence of Streptococcus iniae 89353, a Virulent Strain Isolated from Diseased Tilapia in Taiwan

exterior, steps leading up to terrace with mosque portal and minaret, 1981minaret is unusually tapered, almost conical Two kilometers east of the Silk Road town of Turfan stands the Amin Mosque with its monumental minaret, the tallest in China. The mosque was built in 1779 during the Qing Dynasty in memory of the Uygur King Amin Khoja (also known as Imin Khoja, Emin Hejo, or Emin Hedro) by his son King Suleiman. The mosque was alternately known as the Su Gong Ta Mosque, or the Mosque of the Su Minaret with reference to Prince Su. His father, King Amin, who died in 1777, had collaborated with Emperors Yongzheng (1723-1736) and Qianlong (1736-1796) to unify Xinjiang and annexed it to the Chinese between 1756-1759 putting an end to local rebellions. The large fortified mosque, raised on a platform, stands alone outside the city, devoid of any auxiliary buildings. It combines the local Xinjiang hypostyle prayer hall (built of mud brick, with brick patterning and arched niches) with influences from Persia and Central Asia, seen mainly in the domineering pishtaq, or tall projecting portal, and the minaret. The imposing pishtaq stands at the center of the mosque's eastern elevation and has a large, arched portal niche, similar to portals of mosques, madrasas and tombs stretching from Persia across Central Asia. It is preceded by a protected terrace that is accessed by a single set of stairs from the street. The pishtaq is decorated on its main façade, and on its sides with rectangular panels containing arched niches similar to the portal of the Aitika Mosque in Kashi. The top tier of the panels are pierced with arched windows on all sides creating a narrow, partially enclosed, gallery atop the pishtaq. A domed octagonal vestibule leads from the portal to the prayer hall. To the right of this vestibule is a rectangular hall with a stairway giving access to the roof. To its left, is a narrow corridor flanked by two rooms that give access to the minaret steps. The prayer hall mostly borrows from the building traditions of the immediate Turfan region. Poplar beams and stone-based poplar columns support the low, flat roof of the large, covered court, which is enveloped by stone galleries on three sides. Two small apertures in the woven vegetal roof of the court allow light into the dimly lit main prayer hall, creating a somber atmosphere. The mihrab is set in a domed room at the center of the qibla wall, with doors to the side galleries and to the main court. The two-bay deep stone galleries surrounding the court recall the structure of Abbasid mosques. Their domes are carried on pointed arches falling on heavy piers. Some bays along the outer ring of the galleries are enclosed into rooms. Unlike the mosques and mausoleums of Kashi, there is minimal sculptural and chromatic decoration inside the King Amin Mosque, which is simply adorned with arched niches carved into the plain mud brick walls. The floor is paved with square cut stone and partially covered with woven mats. The mihrab chamber is covered with a large conical dome, the drum of which is encircled with windows. The drum sits upon an octagonal base bearing blind arches gracefully aligned with the doorways, corners and the mihrab niche. This western qibla dome is balanced at the eastern end of the prayer hall by the rounded dome of the entry vestibule. A mausoleum in the cemetery adjoining the qibla wall is said to be that of a foreign saint, and is a popular pilgrimage site. Located at the southeast corner of the mosque, the minaret is the tallest in China at forty-four meters. Its circular shaft measures fourteen meters across and tapers down to 2.8 meters in diameter at the top. The spiraling internal support also serves as a stairway with seventy-two steps for the imam to perform the call to prayer from a room with latticed windows at the top. The ornamental brickwork of the tower consists of fifteen bands of various widths and patterns. The fine precision of the bricklaying creates a rich texture that is reminiscent of the fine brickwork of the world renowned Kalyan, or Poi Minaret in Bukhara. A Uygur architect named Ibrahim is said to have designed the minaret of the Great Mosque of King Amin. The Great Mosque of King Amin, like other Uygur mosques of the Xinjiang Province, is closer in style and decoration to Uzbek and other Central Asian building traditions than to those of the Hui. The mosque has been closed to prayer since 1992, when it was placed under protection by the Chinese government.Sources: Chang, Jing Qi. 1982. Islamic Architecture in China. In The Changing Rural Habitat; Volume 2 : Background Papers. Brian Brace Taylor (ed). Singapore: Concept Media/The Aga Khan Award for Architecture, 74. http://archnet.org/library/documents/one-document.tcl?document_id=4279 [Accessed October 22, 2004] Dazhang, Sun. 2003. Ancient Chinese Architecture: Islamic Buildings. New York: Springer-Verlag/Wien, 146, 166. Fiala, Robert D. 2004. "Emin Minaret". Asian Historical Architecture Website. http://www.orientalarchitecture.com/turpan/eminminaretindex.htm [Accessed October 22, 2004] Loubes, Jean-Paul. 1998. Architecture et Urbanisme de Turfan: Une Oasis du Turkestan Chinois. Paris: L'Harmattan, 169. Martin Frishman and Hasan-Uddin Khan, eds. 1994. The Mosque: History, Architectural Development and Regional Diversity. London: Thames and Hudson, 128. Petersen, Andrew. 1996. "China". In Dictionary of Islamic Architecture. London: Routledge, 52-54. http://archnet.org/library/dictionary/entry.tcl?entry_id=DIA0074 [Accessed October 22, 2004] Zhang, Jing-qui. 1982. "Mosques of Northern China". In MIMAR 3: Architecture in Development. Singapore: Concept Media Ltd, 58, 67. http://archnet.org/library/documents/one-document.tcl?document_id=4433 [Accessed October 22, 2004