Impact of Schistosoma japonicum Infection on Collagen-Induced Arthritis in DBA/1 Mice: A Murine Model of Human Rheumatoid Arthritis

BACKGROUND: The hygiene hypothesis suggests that helminth infections prevent a range of autoimmune diseases. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the effects of S. japonicum infection on collagen-induced arthritis (CIA), male DBA/1 mice were challenged with unisexual or bisexual S. japonicum cercariae two weeks prior to bovine type II collagen (CII) immunization or at the onset of CIA. S. japonicum infection prior to CII immunization significantly reduced the severity of CIA. ELISA (enzyme linked immunosorbent assay) showed that the levels of anti-CII IgG and IgG2a were reduced in prior schistosome-infected mice, while anti-CII IgG1 was elevated. Splenocyte proliferation against both polyclonal and antigen-specific stimuli was reduced by prior schistosome infection as measured by tritiated thymidine incorporation ((3)H-TdR). Cytokine profiles and CD4(+) T cells subpopulation analysis by ELISA and flow cytometry (FCM) demonstrated that prior schistosome infection resulted in a significant down-regulation of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β and IL-6) and Th1 cells, together with up-regulation of the anti-inflammatory cytokine IL-10 and Th2 cells. Interestingly, the expansion of Treg cells and the reduction of Th17 cells were only observed in bisexually infected mice. In addition, prior schistosome infection notably reduced the expression of pro-inflammatory cytokines and receptor activator of NF-κB ligand (RANKL) in the inflamed joint. However, the disease was exacerbated at one week after infection when established CIA mice were challenged with bisexual cercariae. CONCLUSION/SIGNIFICANCE: Our data provide direct evidence that the Th2 response evoked by prior S. japonicum infection can suppress the Th1 response and pro-inflammatory mediator and that bisexual infection with egg-laying up-regulates the Treg response and down-regulates the Th17 response, resulting in an amelioration of autoimmune arthritis. The beneficial effects might depend on the establishment of a Th2-dominant response rather than the presence of the eggs. Our results suggest that anti-inflammatory molecules from the parasite could treat autoimmune diseases

Influence of Heat Treatment on the Morphologies of Copper Nanoparticles Based Films by a Spin Coating Method

We have investigated the influence of heat treatment on the morphologies of copper nanoparticles based films on glass slides by a spin coating method. The experiments show that heat treatment can modify the sizes and morphologies of copper nanoparticles based films on glass slides. We suggest that through changing the parameters of heat treatment process may be helpful to vary the scattering and absorbing intensity of copper nanoparticles when used in energy harvesting/conversion and optical devices

Garnierite mineralization from a serpentinite-derived lateritic regolith, Sulawesi Island, Indonesia: Mineralogy, geochemistry and link to hydrologic flow regime

Garnierite represents a significant nickel ore in many lateritic Ni deposits worldwide. To gain a better understanding of its nature and origin, a well-developed garnierite-hosting transect from the Kolonodale area of East Sulawesi, Indonesia, has been investigated using field geology, mineralogy and geochemical data. Garnierite occurs mainly in veins in the lower saprolite of a serpentinite-derived regolith. Mineralogically, it can be determined as an intimate mixture of Ni-rich serpentine-like (lizardite-Nepouite) and talc-like (kerolite-pimelite) phases. Results of EMP analyses indicate that Ni is preferentially enriched in the talc-like phases rather than the serpentine-like phases. A sequential precipitation of mineral phases progressively enriched in Ni and Si to form garnierite during weathering is suggested. The Ni-lizardite (2.63-8.49 wt% Ni) with elevated Fe (4.02-6.44 wt %) may have been inherited from saprolite in a first instance and enriched in Ni by cation exchange processes. Newly precipitated minerals are kerolite-pimelite (7.84-23.54 wt% Ni) and then followed by Ni-free quartz. Minor amount of Nepouite (23.47-28.51 wt% Ni) occur in laths along shrinkage cracks of previously formed minerals, indicating a late stage paragenetic sequence. With emphasis on a hydrologic consideration, indicators of a preferential flow regime are identified in the garnierite-hosting regolith, including: (i) non-uniform pattern of the garnierite field occurrence, (ii) syn-weathering active nature of the garnierite-hosting structures, (iii) close relationship between the garnierite occurrence and vertical FeeMn oxides pipes as well as FeeMn oxides patched areas, and (iv) specific physico-chemical property of the garnierite location with higher organic matter concentrations but lower pH values compared to surroundings. It is proposed that the origin of garnierite is closely linked to a preferential flow of oversaturated solutions through accessible conduits in the regolith. Garnierite features as colloidal nature, high organic matter and low pH are key-parameters in metal transport and deposition

Loss of miR-638 in vitro promotes cell invasion and a mesenchymal-like transition by influencing SOX2 expression in colorectal carcinoma cells

BACKGROUND: Colorectal carcinoma (CRC) is a major cause of cancer mortality. The aberrant expression of several microRNAs is associated with CRC progression; however, the molecular mechanisms underlying this phenomenon are unclear. METHODS: miR-638 and SRY-box 2 (SOX2) expression levels were detected in 36 tumor samples and their adjacent, non-tumor tissues from patients with CRC, as well as in 4 CRC cell lines, using real-time quantitative RT-PCR (qRT-PCR). SOX2 expression levels were detected in 90 tumor samples and their adjacent tissue using immunohistochemistry. Luciferase reporter and Western blot assays were used to validate SOX2 as a target gene of miR-638. The regulation of SOX2 expression by miR-638 was assessed using qRT-PCR and Western blot assays, and the effects of exogenous miR-638 and SOX2 on cell invasion and migration were evaluated in vitro using the HCT-116 and SW1116 CRC cell lines. RESULTS: We found that miR-638 expression was differentially impaired in CRC specimens and dependent on tumor grade. The inhibition of miR-638 by an antagomiR promoted cell invasion and a mesenchymal-like transition (lamellipodium stretching increased and cell-cell contacts decreased, which was accompanied by the suppression of the epithelial cell marker ZO-1/E-cadherin and the upregulation of the mesenchymal cell marker vimentin). A reporter assay revealed that miR-638 repressed the luciferase activity of a reporter gene coupled to the 3′-untranslated region of SOX2. miR-638 overexpression downregulated SOX2 expression, and miR-638 inhibition upregulated SOX2 expression. Moreover, miR-638 expression levels were correlated inversely with SOX2 mRNA levels in human CRC tissues. The RNAi-mediated knockdown of SOX2 phenocopied the invasion-inhibiting effect of miR-638; furthermore, SOX2 overexpression blocked the miR-638-induced CRC cell transition to epithelial-like cells. CONCLUSIONS: These results demonstrate that the loss of miR-638 promotes invasion and a mesenchymal-like transition by directly targeting SOX2 in vitro. These findings define miR-638 as a new, invasion-associated tumor suppressor of CRC

Rheumatoid Arthritis Naive T Cells Share Hypermethylation Sites With Synoviocytes.

ObjectiveTo determine whether differentially methylated CpGs in synovium-derived fibroblast-like synoviocytes (FLS) of patients with rheumatoid arthritis (RA) were also differentially methylated in RA peripheral blood (PB) samples.MethodsFor this study, 371 genome-wide DNA methylation profiles were measured using Illumina HumanMethylation450 BeadChips in PB samples from 63 patients with RA and 31 unaffected control subjects, specifically in the cell subsets of CD14+ monocytes, CD19+ B cells, CD4+ memory T cells, and CD4+ naive T cells.ResultsOf 5,532 hypermethylated FLS candidate CpGs, 1,056 were hypermethylated in CD4+ naive T cells from RA PB compared to control PB. In analyses of a second set of CpG candidates based on single-nucleotide polymorphisms from a genome-wide association study of RA, 1 significantly hypermethylated CpG in CD4+ memory T cells and 18 significant CpGs (6 hypomethylated, 12 hypermethylated) in CD4+ naive T cells were found. A prediction score based on the hypermethylated FLS candidates had an area under the curve of 0.73 for association with RA case status, which compared favorably to the association of RA with the HLA-DRB1 shared epitope risk allele and with a validated RA genetic risk score.ConclusionFLS-representative DNA methylation signatures derived from the PB may prove to be valuable biomarkers for the risk of RA or for disease status

Prevention of post-surgical abdominal adhesions by a novel biodegradable thermosensitive PECE hydrogel.

<p>Abstract</p> <p>Background</p> <p>Post-operative peritoneal adhesions are common and serious complications for modern medicine. We aim to prevent post-surgical adhesions using biodegradable and thermosensitive poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel. In this work, we investigated the effect of PECE hydrogel on preventing post-surgical abdominal adhesions in mouse and rat models.</p> <p>Results</p> <p>The PECE hydrogel in sol state could be transformed into gel in less than 20 s at 37°C. In addition, the PECE hydrogel could be easily adhered to the damaged peritoneal surfaces, and be gradually degraded and absorbed by the body within 14 days along with the healing of peritoneal wounds. A notable efficacy of the PECE hydrogel in preventing peritoneal adhesions was demonstrated in the animal models. In contrast, all untreated animals developed adhesions requiring sharp dissection. Furthermore, no significant histopathological changes were observed in main organs of the hydrogel-treated animals.</p> <p>Conclusion</p> <p>Our results suggested that the thermosensitive PECE hydrogel was an effective, safe, and convenient agent on preventing post-surgical intro-abdominal adhesions.</p