Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic mice

OBJECTIVE: To investigate the antifibrotic effects of crocetin in scleroderma fibroblasts and in sclerotic mice. METHODS: Skin fibroblasts that were isolated from three systemic scleroderma (SSc) patients and three healthy subjects were treated with crocetin (0.1, 1 or 10 μM). Cell proliferation was measured with an MTT assay. Alpha-smooth muscle actin was detected via an immunohistochemical method. Alpha 1 (I) procollagen (COL1A1), alpha 1 (III) procollagen (COL3A1), matrix metalloproteinase (MMP)-1 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA levels were measured using real-time PCR. SSc mice were established by the subcutaneous injection of bleomycin. Crocetin (50 mg/kg/d) was injected intraperitoneally for 14 days. Dermal thickness and lung fibrosis were assessed with Masson's trichrome staining. Plasma ET-1 was detected with an enzyme-linked immunosorbent assay (ELISA). Skin and lung ET-1 and COL1A1 mRNA levels were measured via real-time PCR. RESULTS: Crocetin inhibited the proliferation of SSc and normal fibroblasts, an effect that increased with crocetin concentration and incubation time. Crocetin decreased the expression of α-SMA and the levels of mRNA for COL1A1, COL3A1 and matrix metalloproteinase-1, while crocetin increased TIMP-1 mRNA levels in both SSc and normal fibroblasts. Skin and lung fibrosis was induced, and the levels of ET-1 in the plasma, skin and lungs were elevated in bleomycin-injected mice. Crocetin alleviated the thickening of the dermis and lung fibrosis; decreased COL1A1 mRNA levels in the skin and lung; and simultaneously decreased ET-1 concentrations in the plasma and ET-1 mRNA levels in the skin and lungs of the bleomycin-induced sclerotic mice, especially during the early phase (weeks 1-3). CONCLUSION: Crocetin inhibits cell proliferation, differentiation and collagen production in SSc fibroblasts. Crocetin alleviates skin and lung fibrosis in a bleomycin-induced SSc mouse model, in part due to a reduction in ET-1

Common Fixed Point for Self-Mappings Satisfying an Implicit Lipschitz-Type Condition in Kaleva-Seikkala's Type Fuzzy Metric Spaces

We first introduce the new real function class ℱ satisfying an implicit Lipschitz-type condition. Then, by using ℱ-type real functions, some common fixed point theorems for a pair of self-mappings satisfying an implicit Lipschitz-type condition in fuzzy metric spaces (in the sense of Kaleva and Seikkala) are established. As applications, we obtain the corresponding common fixed point theorems in metric spaces. Also, some examples are given, which show that there exist mappings which satisfy the conditions in this paper but cannot satisfy the general contractive type conditions

Two new species of the genus Bothropolys Wood, 1862 (Chilopoda: Lithobiomorpha: Lithobiidae) from China

The present paper deals with two new species of the genus Bothropolys Wood, 1862 (Lithobiomorpha: Lithobiidae), recently discovered in China. Bothropolys stoevi sp. n. was found in Hebei and Shanxi Provinces, and Bothropolys edgecombei sp. n.was found in Sichuan Province.We present a key and distributional map of the Chinese Bothropolys species

Effects of acupuncture on rheumatoid arthritis: a systematic review and meta-analysis

Background: The aim of this study was to evaluate the efficacy of acupuncture for treating rheumatoid arthritis (RA).Materials and Methods: The literature were searched using 6 databases, including Pubmed, Embase, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP and Wanfang database up to December 2013, without language restrictions. All randomized clinical trials (RCTs) comparing acupuncture treatment with non-acupuncture treatment of RA was considered. Methodological quality was assessed using the Jadad score.Results: After strict screening, a total of 21 studies containing 1772 participants were included. The meta-analysis indicated that a significant benefit of acupuncture compared with non-acupuncture on improving the symptoms of RA (pooled RR = 1.19, 95% CI 1.08–1.31, Z = 3.47, P = 0.001). In the subgroup analysis, 9 RCTs showed significant effects of acupuncture for response rate compared with western medicine (RR = 1.26, 95% CI 1.02–1.55, Z = 2.19, P = 0.028); 5 RCTs showed significant effects of acupuncture plus traditional Chinese drug compared with traditional Chinese drug (RR = 1.17, 95% CI 1.07–1.29, Z = 3.31, P = 0.001); 5 RCTs showed beneficial effects of acupuncture plus western medicine compared with western medicine (RR = 1.27, 95% CI 1.06–1.53, Z = 2.56 P = 0.01).Conclusion: This meta-analysis demonstrates that acupuncture may have a favorable effect on treating RA. However, the evidence was limited by the small sample size and the low methodological quality. Considering the potential of acupuncture, more researches and well-designed, rigorous and large clinical trials are needed.Key words: Traditional Chinese Medicine, Acupuncture, Rheumatoid arthritis, Meta-analysi

LAS0811: From Combinatorial Chemistry to Activation of Antioxidant Response Element

The antioxidant response element (ARE) and its transcription factor, nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), are potential targets for cancer chemoprevention. We sought to screen small molecules synthesized with combinatorial chemistry for activation of ARE. By high-throughput screening of 9400 small molecules from 10 combinatorial chemical libraries using HepG2 cells with an ARE-driven reporter, we have identified a novel small molecule, 1,2-dimethoxy-4,5-dinitrobenzene (LAS0811), as an activator of the ARE. LAS0811 upregulated the activity of NAD(P)H:quinone oxidoreductase 1 (NQO1), a representative antioxidative enzyme regulated by ARE. It enhanced production of an endogenous reducing agent, glutathione (GSH). In addition, LAS0811 induced expression of heme oxygenase 1 (HO1), which is an ARE-regulated enzyme with anti-inflammatory activity. Furthermore, LAS0811 reduced cell death due to the cytotoxic stress of a strong oxidant, t-butyl hydroperoxide (t-BOOH). Mechanistically, LAS0811 upregulated the expression of Nrf2 and promoted its translocation into the nuclei leading to subsequent ARE activation. Taken together, LAS0811 is a novel activator of the ARE and its associated detoxifying genes and, thus, a potential agent for cancer chemoprevention