Intra-Articular Injection of (-)-Epigallocatechin 3-Gallate (EGCG) Ameliorates Cartilage Degeneration in Guinea Pigs with Spontaneous Osteoarthritis.

Osteoarthritis (OA) is the most prevalent joint disease that causes an enormous burden of disease worldwide. (-)-Epigallocatechin 3-gallate (EGCG) has been reported to reduce post-traumatic OA progression through its anti-inflammatory property. Aging is the most crucial risk factor of OA, and the majority of OA incidences are related to age and not trauma. In this study, we assess whether EGCG can ameliorate cartilage degradation in primary OA. In an in-vitro study, real-time PCR was performed to assess the expression of genes associated with human articular chondrocyte homeostasis. A spontaneously occurring OA model in guinea pigs was used to investigate the effect of EGCG in vivo. OA severity was evaluated using Safranin O staining and Osteoarthritis Research Society International (OARSI) scores, as well as by immunohistochemical (IHC) analysis to determine the protein level of type II collagen (Col II), matrix metalloproteinase 13 (MMP-13), and p16 ink4a in articular cartilage. In the in-vitro study, EGCG increased the gene expression of aggrecan and Col II and decreased the expression of interleukin-1, cyclooxygenase 2, MMP-13, alkaline phosphatase, Col X, and p16 Ink4a; EGCG treatment also attenuated the degraded cartilage with a lower OARSI score. Meanwhile, IHC results showed that EGCG exerted an anti-OA effect by reducing ECM degradation, cartilage inflammation, and cell senescence with a less-immunostained Col II, MMP-13, and p16 Ink4a. In conclusion, these findings suggest that EGCG may be a potential disease-modifying OA drug for the treatment of primary OA.

Antigenemia and cytokine expression in rotavirus gastroenteritis in children.

BACKGROUND: Antigenemia is commonly found in children with rotavirus infection, although its clinical significance is undetermined. The aim of this study was to evaluate the association of antigenemia with clinical manifestations and cytokine profiles in children infected by rotavirus. METHODS: In total, 68 children hospitalized with rotavirus gastroenteritis were enrolled. Serum samples were collected for detection of antigenemia and viremia. Clinical, laboratory and demographic data were analyzed. Proinflammatory, Th1 and Th2 cytokines were evaluated by bead-based flow cytometry. RESULTS: Antigenemia and viremia were found in 45.6% (n = 31) and 5.9% (n = 4) of the 68 rotavirus-infected children, respectively. The mean age of the antigenemia group was significantly greater than that of the non-antigenemia group (43.5 vs. 27.3 months; p = 0.034). The antigenemia group had a significantly shorter length of hospitalization (4.8 vs. 5.8 days; p = 0.0354) in comparison with the non-antigenemia group, and antigenemia was inversely associated with the length of hospitalization (ß = 0.31, p = 0.021). A significantly higher tumor necrosis factor (TNF)-ß level was found in the patients with antigenemia than those without (236.7 vs. 29.2 pg/mL, p = 0.026). The severity of disease and the rate of extra-intestinal manifestations did not differ between the groups. Viremia was associated with a higher fever (p = 0.012). CONCLUSIONS: Antigenemia was positively correlated with shorter hospital stay in children with rotavirus infection. Enhanced innate and T-cell-mediated immunity evidenced by up-regulation of TNF-ß was found in patients with antigenemia.

Transgenic zebrafish line with over-expression of Hedgehog on the skin: a useful tool to screen Hedgehog-inhibiting compounds.

We generated a transgenic line Tg(k18:shh:RFP) with overexpression of Sonic hedgehog in the skin epidermis. By 5 day-post-fertilization (dpf), many epidermal lesions were clearly observed, including a swollen yolk sac, epidermis growth malformation around the eyes and at the basement of the pectoral fins. Skin histology revealed embryos derived from Tg(k18:shh:RFP) displayed an elevated Nuclear/Cytoplasmic ratio and pleomorphic nuclei compared to their wild type littermates, suggesting the abnormal growth pattern on the epidermis of Tg(k18:shh:RFP) embryos were dysplasia. Later (by 7 dpf), Tg(k18:shh:RFP) embryos displayed broader pectoral fins which are similar to the polydactyly phenotypes of Nevoid basal cell carcinoma syndrome (NBCCS)/Gorlin patients and polydactylous mice. In addition, treatment with cyclopamine is able to enhance and prolong the survival rates and survival durations of Tg(k18:shh:RFP) embryos. In conclusion, this unique Tg(k18:shh:RFP) fish line, should be an excellent experimental animal for screening for a lower toxicity level of the new Hh-inhibitor and can even be used as a new anti-cancer drug-screening platform.