Tag: 夜上海论坛YX

Living hydrogel can help heal intestinal wounds

first_img The IBD–gut bug connection Could open the door to new bioactive healing strategies In their new study, the team further built on these findings by introducing the machinery for producing one of the mucoadhesive hydrogels based on TFF3 into an E. coli Nissle strain that is a normal gut bacterium that can thrive in the colon and cecum sections of the intestinal tract affected by IBD, and is currently sold in many commercial probiotic formulations. “We found that the newly engineered Nissle bacteria, when given orally, also populated and resided in the intestinal tract, and that their curli fibers integrated with the intestinal mucus layer,” said first author Pichet Praveschotinunt, who is a graduate student mentored by Joshi.“When we induced colitis in the colons of mice by orally administering the chemical dextran sodium sulfate, animals that had received the PATCH-generating E. coli Nissle strain by daily rectal administration starting three days prior to chemical treatment had significantly faster healing and lower inflammatory responses, which caused them to lose much less weight and recover faster compared to control animals,” said Praveschotinunt. “Their colon epithelial mucosa displayed a more normal morphology and lower numbers of infiltrating immune cells.”Joshi and his team think that their approach could be developed as a companion therapy to existing anti-inflammatory, immuno-suppressant, and antibiotic therapies to help minimize patients’ exposure to the drugs and potentially provide protection against IBD relapses.Additional authors on the study are Wyss Institute researchers Ilia Gelfat, Franziska Bahl, and David B. Chou.The study was supported by a grant from the National Institutes of Health, funds from Harvard’s Wyss Institute for Biologically Inspired Engineering and the Blavatnik Biomedical Accelerator, and a royal Thai government scholarship. New findings reveal how inflammatory bowel disease disrupts the microbiome The Daily Gazette Sign up for daily emails to get the latest Harvard news.center_img Related About 1.6 million people in the U.S.  have an incurable inflammatory bowel disease (IBD) such as Crohn’s or ulcerative colitis, and 70,000 new cases are diagnosed each year.IBD patients suffer from pain, extreme discomfort, and numerous other symptoms caused by continuously relapsing and remitting inflammatory lesions in the layer of cells that lines the intestinal lumen (mucosa). The exact causes for IBD still are poorly understood, but it is clear that a misdirected immune system is at work, and that certain components of the microbial community in our gut, known as the intestinal microbiome, and environmental factors contribute to its destructive forces.While anti-inflammatory drugs can dampen acute inflammation and antibiotics can fight local infections when IBD episodes flare up, their use also comes at a cost. Anti-inflammatory drugs can have severe side effects, and antibiotics can disrupt the beneficial parts of the microbiome. Importantly, there are no wound treatments available that could be applied to inflamed lesions directly from inside the gut lumen in order to speed up healing and minimize use of those drugs.Now, a research team at Harvard’s Wyss Institute for Biologically Inspired Engineering led by Neel Joshi has developed a living-material approach that uses a strain of genetically engineered E.coli Nissle gut bacteria as a locally acting probiotic. The engineered bacteria produce a network of nanofibers that directly binds to mucus to fill inflamed areas like a patch, shielding them from gut microbes and environmental factors. This probiotic-based therapeutic strategy protected mice against the effects of colitis induced by a chemical agent and promoted mucosal healing. Their findings are reported in Nature Communications.“With this ‘living therapeutics’ approach, we created multivalent biomaterials that are secreted by resident engineered bacteria on-site and attach to many mucus proteins at a time — firmly adhering to the viscous and otherwise moving mucus layer, which is a challenging thing to do,” said Joshi. “The Probiotic Associated Therapeutic Curli Hybrids (PATCH) approach, as we named it, creates a biocompatible, mucoadhesive coating that functions as a stable, self-regenerating Band-Aid and provides biological cues for mucosal healing.”,Joshi presently is a core faculty member of the Wyss Institute and associate professor at Harvard’s Paulson School of Engineering and Applied Sciences (SEAS), and will shortly be appointed as a professor at Northeastern University in Boston.In previous work, Joshi’s group demonstrated that self-regenerating bacterial hydrogels firmly attached to mucosal surfaces ex vivo, and, when orally given to mice, withstood the harsh pH and digestive conditions of the stomach and small intestine without affecting the animals’ health. To fabricate them, his team programmed a laboratory E. coli strain to synthesize and secrete a modified CsgA protein, which as part of E. coli’s “curli” system assembles into long nanofibers at the outer surface of the bacteria. “To enable mucus adhesion, we fused CsgA to the mucus-binding domain of different human trefoil factors (TFFs), proteins that occur naturally in the intestinal mucosa and bind to mucins, the major mucus proteins present there. The secreted fusion proteins form a water-storing mesh with tunable hydrogel properties,” said co-author Anna Duraj-Thatte, a postdoctoral fellow working with Joshi. “This turned out to be a simple and robust strategy to produce self-renewing, mucoadhesive materials with long residence times in the mouse intestinal tract.” Probiotic hydrogels heal gut wounds that other treatments can’t reachlast_img read more

Bruce Logan: Same-sex marriage threatens civil liberty

first_imgNZ Herald 29 Aug 2012Same sex marriage is not an issue of equality nor the success of any couple’s marriage. It is not about the value or validity of homosexuality. The issue is about the link between the state and marriage in civil society. Who decides what marriage is and what it’s for?Marriage is neither essentially religious nor a product of tradition. It is not the child of the state.Neither is marriage what Lynne Featherstone the British Equalities Minister claims. “Marriage is a right of passage for couples who want to show they are in a committed relationship, for people who want to show they have found love and wish to remain together until death do them part.” Her historical vision is limited; her logic is deficient and her fusion of the Anglican Prayer Book with modern idiom disingenuous.Marriage is the consequence of who we are. We do not make it; it makes us. Marriage would not exist if there were not two complementary sexes. And that’s why it does exist.We are male and female. In the simple and hopeful business of being alive we have children in a union of consenting responsibility, love and thankfulness.It is the fusing of two opposite halves of the human being through which new life may be created.That some couples decide not to get married does not change the biology. That some cannot have children or decide not to is beside the point.The so-called conservative case for same-sex marriage favoured by the British Prime Minister (and apparently by our own Prime Minister) tumbles out of a category error. “Marriage is a good thing. It stabilises the lives of those who participate; especially men. Therefore they should be able to marry each other if they are committed.”But as soon as same-sex marriage is granted, marriage has been changed to something profoundly different; from an institution prior to the state to one determined by the state.Of course the state has had regulations around marriage for a very long time. But with the advent of same-sex marriage we have given the state a role it never had.If the state defines marriage the family is no longer an independent institution of civil society declaring daily to the state its limitations. While we are a long way from Stalinism in New Zealand this was the kind of power Stalin wanted.If the state passes a law that changes the nature of marriage, and consequently family, then every citizen’s liberty is endangered. Why? That area of most intimate human life that was once outside the power of the state to control will be watered down. In becoming the author of marriage the state must eventually erode religious freedom and then freedom of speech.The ‘new marriage’ will become an institution that the state must enforce. Any exemption given initially to the church will be temporary and dependent only on threatened moral sensitivities. It will not be enough for the church to be good or even right when all the social forces are moving against it.Human rights were once seen as a cornerstone of liberty because they were the consequence of a free society aware of state limits. They protected the independent spheres of authority in civil society (marriage, family and religion and others).If marriage becomes what the state determines citizens will no longer have any legal, or ultimately moral framework independent of the state to argue their case about family form. Families will become what the state decides. In France this is probably the pivotal constitutional issue around which the same sex marriage debate spins.It is doubtful there is any society known to history or anthropology where social order has not been based on marriage between a man and a woman.It has always been an historical and universal understanding of a binding contract to enhance social order and encourage responsible child care. Societies that fail to understand this devalue their children. We should know that. We have plenty of evidence.We have never had such a plethora of data pointing out the fundamental economic, social and psychological benefits of vigorous and enduring married families. Marriage is pivotal to intergenerational order. Without it we have a shambles and increasing poverty.* Bruce Logan is a former Auckland schoolteacher now living in France.http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10829995last_img read more