Ulcerative colitis (UC) is a common chronic remitting disease driven through altered immune responses with production of inflammatory cytokines. Oxidant/antioxidant balance is also suggested to be an important factor for the recurrence and progression of UC. Maggots are known as a traditional Chinese medicine also known as “wu gu chong.” NF-E2-related factor-2 (Nrf2) transcription factor regulates the oxidative stress response and also represses inflammation. The aim of this study was to investigate the effects of maggot extracts on the amelioration of inflammation and oxidative stress in a mouse model of dextran sulfate sodium- (DSS-) induced colitis and evaluate if the maggot extracts could repress inflammation and oxidative stress using RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). In the present study, we found that the maggot extracts significantly prevented the loss of body weight and shortening of colon length in UC induced by DSS. Furthermore, DSS-induced expression of proinflammatory cytokines at both mRNA and protein levels in the colon was also attenuated by the maggot extracts. In addition, the maggot extracts could significantly suppress the expression of interleukin- (IL-) 1β, IL-6, TNF-α, NFκB p65, p-IκB, p22-phox, and gp91-phox in LPS-stimulated RAW 264.7 cells and colonic tissues. The maggot extracts increased the level of Nrf2 and prevented the degradation of Nrf2 through downregulating the expression of Keap1, which resulted in augmented levels of HO-1, SOD, and GSH-Px and reduced levels of MPO and MDA. However, after administering an Nrf2 inhibitor (ML385) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of the maggot extracts in mice with colitis and RAW 264.7 cells. Taken together, our data for the first time confirmed that the maggot extracts ameliorated inflammation and oxidative stress in experimental colitis via modulation of the Nrf2/HO-1 pathway. This study sheds light on the possible development of an effective therapeutic strategy for inflammatory bowel diseases.

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Intestinal fibrosis is induced by excessive myofibroblast proliferation and collagen deposition, which has been regarded as a general pathological feature in inflammatory bowel disease (IBD). Therefore, identifying clinical markers and targets to treat and prevent intestinal fibrosis is urgently needed. The traditional Chinese medicine maggot, commonly known as “wu gu chong”, has been shown to reduce oxidative stress and alleviate inflammation in chronic colitis. This study investigated the mechanisms underlying the effects of maggot extract (ME) on inflammation-associated intestinal fibrosis in TGF-β1-stimulated human intestinal fibroblasts (CCD-18Co cells) and dextran sodium sulphate (DSS)-induced chronic colitis murine model. To assess the severity of inflammation and fibrosis, histological and macroscopic evaluation were carried out. The results showed that ME was a significant inhibitor of body weight loss and colon length shortening in mice with chronic colitis. In addition, ME suppressed the intestinal fibrosis by downregulating TGF-β1/SMADs pathway via upregulation of Nrf2 expression at both protein and mRNA levels. ME markedly increased the expression of Nrf2, thus resulting in a higher level of HO-1. After treatment with Nrf2 inhibitor (ML385) or siRNA-Nrf2 for deactivating Nrf2 pathway, the protective effects of ME were abolished both in vitro and in vivo. Moreover, the histopathological results for the major organs of DSS mice treated with ME showed no signs of clinically important abnormalities. Treatment with ME had no effect on the viability of CCD-18Co cells, suggesting its low in vitro cytotoxicity. Furthermore, ME could mediate intestine health by keeping the balance of the gut microbes through the enhancement of beneficial microbes and suppression of pathogenic microbes. In conclusion, this is the first ever report demonstrating that ME ameliorates inflammation-associated intestinal fibrosis by suppressing TGF-β1/SMAD pathway via upregulation of Nrf2 expression. Our findings highlight the potential of Nrf2 as an effective therapeutic target for alleviating intestinal fibrosis.

While few studies have explored library anxiety among international graduate students in the United States, Jiao and Onwuegnuzie's study (1999) of international graduate and undergraduate students identified mechanical barriers as the greatest source of library anxiety among international students. Building on this, the current pilot study investigated the level of library anxiety among 15 international graduate students in the United States, using a modified version of Bostick's (1992) Library Anxiety Scale (LAS) with a proposed Language & Cultural Barriers subscale. Findings from the pilot study revealed that mechanical barriers were the smallest source of library anxiety, and affective and staff barriers were the greatest sources of library anxiety. No significant gender or disciplinary differences were found in terms of the level of library anxiety among international graduate students. The results of this pilot study also provided the basis for the refinement of instrument.

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: Based on three domains of colchicine-site which is conducive to the combination with small molecular compounds, colchicine-site on the tubulin has become a popular target for antitumor, that resulted in a great number of tubulin inhibitors binding to colchicine-site were reported and evaluated over the past years. Here, tubulin inhibitors targeting colchicine-site and their application to antitumor were reviewed from 2015 to 2019. Tubulin inhibitors were classified to ten categories according to structural features, as colchicine derivates, CA-4 analogues, chalcone analogues, coumarin analogs, indole hybrids, quinoline and quinazoline analogs, lignan and podophyllotoxin derivatives, phenothiazine analogs, N-heterocycle hybrids and others. Most of them possessing strong antitumor activity including antiproliferative potential against multi-drug-resistant (MDR) cell lines and anti-vascular properties both in vitro and in vivo. Therefore, in-depth analysis, lots of compounds were listed in tables as multi-target inhibitors, anti-MDR compounds, and inhibitors bearing antitumor activity in vivo. The latest research progress of tubulin inhibitors was demonstrated in this review, providing valuable reference and convenience for the research on tubulin inhibitors in future.