Therapeutic Targeting of Nrf2 Signaling by Maggot Extracts Ameliorates Inflammation-Associated Intestinal Fibrosis in Chronic DSS-Induced Colitis.

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-ß1-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-ß1/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-ß1/SMAD pathway via upregulation of Nrf2 expression. Our findings highlight the potential of Nrf2 as an effective therapeutic target for alleviating intestinal fibrosis.

Building a transgenic sexing strain for genetic control of the Australian sheep blow fly Lucilia cuprina using two lethal effectors.

BACKGROUND: The sterile insect technique (SIT) has been successfully used in many pest management programs worldwide. Some SIT programs release both sexes due to the lack of genetic sexing strains or efficient sex separation methods but sterile females are ineffective control agents. Transgenic sexing strains (TSS) using the tetracycline-off control system have been developed in a variety of insect pests, from which females die by either of two commonly used lethal effectors: overexpression of the transcription factor tetracycline transactivator (tTA) or ectopic expression of a proapoptotic gene, such as head involution defective (hid). The lethality from tTA overexpression is thought to be due to "transcriptional squelching", while hid causes lethality by induction of apoptosis. This study aims to create and characterize a TSS of Lucilia cuprina, which is a major pest of sheep, by combining both lethal effectors in a single transgenic strain. RESULTS: Here a stable TSS of L. cuprina (DH6) that carries two lethal effectors was successfully generated, by crossing FL3#2 which carries a female-specific tTA overexpression cassette, with EF1#12 which carries a tTA-regulated LshidAla2 cassette. Females with one copy of the FL3#2 transgene are viable but up to 99.8% of homozygous females die at the pupal stage when raised on diet that lacks tetracycline. Additionally, the female lethality of FL3#2 was partially repressed by supplying tetracycline to the parental generation. With an additional LshidAla2 effector, the female lethality of DH6 is 100% dominant and cannot be repressed by maternal tetracycline. DH6 females die at the late-larval stage. Several fitness parameters important for mass rearing such as hatching rate, adult emergence and sex ratio were comparable to those of the wild type strain. CONCLUSIONS: Compared to the parental FL3#2 strain, the DH6 strain shows stronger female lethality and lethality occurs at an earlier stage of development. The combination of two tTA-dependent lethal effectors could improve strain stability under mass rearing and could reduce the risk of resistance in the field if fertile males are released. Our approach could be easily adapted for other pest species for an efficient, safe and sustainable genetic control program.

Desenvolvimento pós-embrionário de Chrysomya putoria (Calliphoridae) em carne equina e sua importância para a entomologia e veterinária forenses / [Post embryonic development of Chrysomya putoria (Calliphoridae) using horse meat and its importance for forensic entomology and veterinary]

Devido à importância médica, veterinária, ambiental e forense do califorídeo Chrysomya putoria (Diptera), foi avaliado o desempenho apresentado por estágios imaturos criados em carne de cavalo. Os espécimes foram colocados em câmaras aclimatizadas reguladas a 30 ºC, 60 ± 10% UR e 14 horas de fotofase. Os estágios larval e pupal concluíram seu desenvolvimento em 4,16 e 4,12 dias, respectivamente. As larvas pós-alimentação e pupas com 24h de idade pesaram, em média, 58,06 e 40,10mg, respectivamente. As taxas de emergência registradas foram de 65% nas condições experimentais propostas. Como os compostos orgânicos voláteis são diferentes na decomposição de um animal para outro, este trabalho e outros realizados com a mesma dieta são os mais apropriados para estimativa de intervalo post mortem envolvendo cavalos.(AU)

Due to medical, veterinary, environmental and forensic importance of the calliphorid Chrysomya putoria (Diptera), the performance presented by immature stages, reared on horse meat, was evaluated. The specimens were placed in acclimatized chambers regulated at 30 ºC, 60 ± 10% RU and 14 hours of photo phase. The larval and pupal stages completed their development in 4, 16 and 4, 12 days, respectively. Post-feeding larvae and aged 24h pupae weight on average 58, 06 and 40, 10 mg, respectively. The emergence rates recorded were 65% under the experimental conditions proposed. As volatile organic compounds are different in the decomposition of one animal to another, this work and others carried out with the same diet are the most appropriate for estimating post-mortem interval involving horses.(AU)