Advanced glycation end products initiate the mutual promoting cycle between centrosome amplification and the release of inflammatory cytokines in human vascular endothelial cells.

Inflammation is implicated in the development of diabetic complications including vascular pathology. Centrosome is known to play a role in cell secretion. We have reported that diabetes can trigger centrosome amplification (CA). Thus, in the present study, we investigated the relationship between CA and the release of proinflammatory cytokines interleukin-1ß, tumor necrosis factor-α and interleukin-6 in hCMEC/D3 human endothelial cells treated with advanced glycation end products (AGEs). We found that AGEs induced CA via PLK4 and increased the biosynthesis of the three cytokines via NF-κB. Importantly, treatment of the cells with AGEs also increased the release of the three cytokines. Inhibiting CA by knockdown of polo like kinase 4 (PLK4) attenuated the cytokine release but not their biosynthesis. Knockdown of the cytokines inhibited the CA, while addition of the cytokines individually to the cell culture increased the protein level of PLK4 and CA to a moderate level. Addition of the three cytokines together into the cell culture markedly enhanced the CA, to a level higher than that in the AGEs-treated group. In conclusion, our results provide the direct evidence that the cytokines can induce CA, and suggest that there is a mutual promoting cycle between CA and cytokine release in the treated samples. It is proposed that the cycle of CA-cytokine release is a candidate biological link between diabetes and its complications such as vascular pathologies.

Th2-related cytokines are associated with Fasciola gigantica infection and evasion in the natural host, swamp buffalo.

The infection of ruminants by Fasciola spp. always induces a non-protective Th2-type immune response. However, little is known about changes in the local and systemic immune environment during F. gigantica migration in buffalo. In this study, native swamp buffaloes were each infected with 500 viable F. gigantica metacercariae. Mesenteric lymph node (MLN), hepatic lymph node (HLN), spleen, and serum samples were collected from control and infected buffaloes at 3, 10, 28, 42, 70, and 98 days post-infection (DPI). The mRNA expression levels of the Th1- and Th2-related cytokines IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IFN-γ, TNF-α, and CD4 were measured during different infection stages in the MLNs, spleens, and HLNs using quantitative real-time PCR (qRT-PCR). Levels of the specific anti-ESP isotype antibodies IgG, IgG1, and IgG2 were used to reflect changes in humoral immunity. The results of this study indicated that swamp buffaloes were susceptible to F. gigantica infection, and that susceptibility to this infection was closely related to the cytokine environment associated with the Th2-type immune response. The MLNs showed a mixed Th1- and Th2-type immune response during the acute infection stages, after which the production of these cytokines returned to normal. Cytokine expression in the HLNs also expressed a mixed Th1- and Th2-type immune response during the early infection stages. When the infection became chronic, the typical Th2 immune response was induced in the HLNs. At the acute infection stages, the spleen exhibited a Th2 immune response. Nevertheless, cytokines associated with the Th1 and Th2 immune responses were upregulated at 98 DPI. In addition, the total IgG and IgG1 of the parasite-specific antibodies increased. This suggested that the Th2-related cytokines and IgG1 induced by F. gigantica infection might mediate successful F. gigantica infection in the natural host, swamp buffalo.

Dietary patterns and the risk of metabolic syndrome in Chinese adults: a population-based cross-sectional study.

OBJECTIVE: Data on dietary patterns in relation to the risk of metabolic syndrome (MetS) in a middle-aged Chinese population are sparse. The present study was performed to determine the major dietary patterns among a population aged 45-59 years and to evaluate their associations with MetS risk in China. DESIGN: Cross-sectional examination of the association between dietary patterns and MetS. Face-to-face interviews were used to assess dietary intake using a validated semi-quantitative FFQ. OR and 95 % CI for MetS were calculated across quartiles of dietary pattern scores using multivariate logistic regression analysis models. SETTING: City of Linyi, Shandong Province, China. SUBJECTS: Adults (n 1918) aged 45-59 years. RESULTS: Three major dietary patterns were identified: traditional Chinese, animal food and high-energy. After adjustment for potential confounders, individuals in the highest quartile of the traditional Chinese pattern had a reduced risk of MetS relative to the lowest quartile (OR=0·72, 95 % CI 0·596, 0·952; P<0·05). Compared with those in the lowest quartile, individuals in the highest quartile of the animal food pattern had a greater risk of MetS (OR=1·28; 95 % CI 1·103, 1·697; P<0·05). No significant association was observed between the high-energy pattern and risk of MetS. CONCLUSIONS: These findings indicate that the traditional Chinese pattern was associated with a reduced risk, while the animal food pattern was associated with increased risk of MetS. Given the cross-sectional nature of our study, further prospective studies are warranted to confirm these findings.

Dynamic expression of cytokine and transcription factor genes during experimental Fasciola gigantica infection in buffaloes.

BACKGROUND: Determining the mechanisms involved in the immune-pathogenesis of the tropical liver fluke, Fasciola gigantica, is crucial to the development of any effective therapeutic intervention. Here, we examined the differential gene expression of cytokines and transcription factors in the liver of F. gigantica-infected buffaloes, over the course of infection. METHODS: Water buffaloes (swamp type) were infected orally with 500 F. gigantica encysted metacercariae. Liver tissue samples were collected 3, 10, 28, 42, 70 and 98 days post-infection (dpi). Levels of gene expression of nine cytokines (IFN-γ, TGF-ß, IL-1ß, IL-4, IL-6, IL-10, IL-12B, IL-13 and IL-17A) and four transcription factors (T-bet, GATA-3, Foxp3 and ROR-γτ) were determined using quantitative real-time PCR (qRT-PCR). We evaluated any correlation between gene expression of these immune-regulatory factors and the severity of liver pathology. RESULTS: Histopathological examination revealed that cellular infiltration, hemorrhage and fibrosis without calcification in the liver parenchyma of infected buffaloes, increased over the course of infection. This progressive pathology was attributed to dysregulated and excessive inflammatory responses induced by infection. The early infection phase (3-10 dpi) was marked by a generalized immunosuppression and elevated TGF-ß expression in order to facilitate parasite colonization. A mixed Th1/Th2 immune response was dominant from 28 to 70 dpi, to promote parasite survival while minimizing host tissue damage. During late infection (98 dpi), the response was biased towards Th1/Treg in order to inhibit the host's Th2 protective response and promote chronic infection. Both IL-10 and IL-17A and the Th17/Treg balance, played key roles in mediating the inflammatory and immunoregulatory mechanisms in the liver during chronic fasciolosis. CONCLUSIONS: Our data showed distinct CD4+ T helper (Th) polarization and cytokine dysregulation in response to F. gigantica infection in water buffaloes over the course of infection. Characterizing the temporal expression profiles for host immune genes during infection should provide important information for defining how F. gigantica adapts and survives in the liver of buffaloes and how host immune responses influence F. gigantica pathogenicity.

Chondrogenic differentiation of ChM-I gene transfected rat bone marrow-derived mesenchymal stem cells on 3-dimensional poly (L-lactic acid) scaffold for cartilage engineering.

We have explored the role of Chondromodulin-I (ChM-I) in chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) in 3-dimensional (3D) scaffold for cartilage tissue engineering. BMSCs of Sprague Dawley (SD) rats were cultured on poly-(L-lactic acid) [PLLA] scaffolds with different pore sizes (80-200 µm, 200-450 µm) with or without surface modification by chitosan. Cell viability, proliferation, and morphology were measured using confocal microscope and the CCK-8 method. Untransfected BMSCs, BMSCs expressing pcDNA3.1(+), BMSCs expressing plasmid pcDNA3.1 (+)/ChM-I were cultured on 3D scaffolds in standard growth medium or transforming growth factor-ß1 (TGF-ß1) supplemented chondrogenic induction medium in vitro for 3 weeks and the expression of collagen type II was determined. Cell-scaffolds constructs were implanted subcutaneously for 3 months in vivo. BMSCs had a higher viability and proliferation in PLLA scaffolds of pore size 200-450 µm than that of 80-200 µm, and surface modification with chitosan did not enhance cell attachment. The ChM-I gene enhanced chondrogenesis and increased collagen type II synthesis. Immunohistochemistry from in vivo study showed enhanced cartilage regeneration in BMSCs expressing pcDNA3.1 (+)/ChM-I on 3D PLLA scaffolds. It also demonstrated that TGF-ß1 might promote chondrogenesis of rat BMSCs by synergizing with the ChM-I gene. ChM-I could be beneficial to future applications in cartilage repair.