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Foulks G.N.,University of Louisville | Foulks G.N.,Louisville Veterans Administration Medical Center | Borchman D.,University of Louisville
Eye and Contact Lens | Year: 2010

Objective: To recount the historic evaluation of meibomian gland dysfunction (MGD) and describe new techniques to monitor disease and therapy. Methods: A review of the literature regarding the description of MGD and the role of abnormalities of meibomian gland secretion in health and disease. Results: Meibomian gland dysfunction is a common clinical condition and is a major cause of evaporative dry eye with associated discomfort, visual disturbance, and contact lens intolerance. Despite the early description of the anatomy and physiology of the meibomian gland, recognition of the importance of the MGD and particularly therapeutic options to treat it has been limited. Conclusions: Improved methods of spectroscopic and chemical analysis of the meibomian gland secretion in health and disease are providing a better understanding of the physical and chemical abnormalities of the meibomian gland secretions and are allowing better evaluation of medical therapies. © 2010 Lippincott Williams & Wilkins.

Zhuang X.,Yangzhou University | Zhuang X.,University of Louisville | Xiang X.,University of Louisville | Grizzle W.,University of Alabama at Birmingham | And 10 more authors.
Molecular Therapy | Year: 2011

In this study, exosomes used to encapsulate curcumin (Exo-cur) or a signal transducer and activator of transcription 3 (Stat3) inhibitor, i.e., JSI124 (Exo-JSI124) were delivered noninvasively to microglia cells via an intranasal route. The results generated from three inflammation-mediated disease models, i.e., a lipopolysaccharide (LPS)-induced brain inflammation model, experimental autoimmune encephalitis and a GL26 brain tumor model, showed that mice treated intranasally with Exo-cur or Exo-JSI124 are protected from LPS-induced brain inflammation, the progression of myelin oligodendrocyte glycoprotein (MOG) peptide induced experimental autoimmune encephalomyelitis (EAE), and had significantly delayed brain tumor growth in the GL26 tumor model. Intranasal administration of Exo-cur or Exo-JSI124 led to rapid delivery of exosome encapsulated drug to the brain that was selectively taken up by microglial cells, and subsequently induced apoptosis of microglial cells. Our results demonstrate that this strategy may provide a noninvasive and novel therapeutic approach for treating brain inflammatory-related diseases. © 2011 The American Society of Gene & Cell Therapy.

Zhang H.-G.,University of Louisville | Zhang H.-G.,Louisville Veterans Administration Medical Center | Zhuang X.,University of Louisville | Sun D.,University of Alabama at Birmingham | And 3 more authors.
Biotechnic and Histochemistry | Year: 2012

The immune system has been reported to suppress the development and progression of neoplastic lesions; however, the exact mechanisms by which neoplastic lesions and the immune system interact are not well understood. Within the last decade, tiny membrane bound particles, approximately 30-100 nm in diameter, have been observed in the blood and other body fluids. These particles, currently called exosomes, are released from many types of tissues including tumors, and they contain and carry many proteins, and mRNAs and microRNA species. We review here how tumors suppress the immune system, especially by the formation of exosomes. Exosomes released from tumors are carried in part by the vascular system to distant cells, which phagocytose them. Depending on the proteins, mRNAs or microRNAs in the exosomes and the cell type, phagocytosis of exosomes may provide a modulating signal to the cell. In the case of exosomes from tumors, uptake of the exosomes by cells of the immune system has been reported to have three main effects: 1) suppression of the number and activity of natural killer cells, 2) suppression of the activity of T cells and 3) suppression of the number and maturation of mature dendritic cells. © 2012 The Biological Stain Commission.

Ju S.,University of Louisville | Mu J.,University of Louisville | Dokland T.,University of Alabama at Birmingham | Zhuang X.,University of Louisville | And 13 more authors.
Molecular Therapy | Year: 2013

Food-derived exosome-like nanoparticles pass through the intestinal tract throughout our lives, but little is known about their impact or function. Here, as a proof of concept, we show that the cells targeted by grape exosome-like nanoparticles (GELNs) are intestinal stem cells whose responses underlie the GELN-mediated intestinal tissue remodeling and protection against dextran sulfate sodium (DSS)-induced colitis. This finding is further supported by the fact that coculturing of crypt or sorted Lgr5 + stem cells with GELNs markedly improved organoid formation. GELN lipids play a role in induction of Lgr5 + stem cells, and the liposome-like nanoparticles (LLNs) assembled with lipids from GELNs are required for in vivo targeting of intestinal stem cells. Blocking β-catenin-mediated signaling pathways of GELN recipient cells attenuates the production of Lgr5 + stem cells. Thus, GELNs not only modulate intestinal tissue renewal processes, but can participate in the remodeling of it in response to pathological triggers. © The American Society of Gene & Cell Therapy.

Liu Y.,University of Alabama at Birmingham | Xiang X.,University of Alabama at Birmingham | Xiang X.,University of Louisville | Zhuang X.,University of Alabama at Birmingham | And 9 more authors.
American Journal of Pathology | Year: 2010

In this study we observed that mice pretreated with tumor exosomes had a significant acceleration of tumor metastasis in the lung. Tumor metastasis correlated significantly with an increase in recruitment of more Myeloid-derived suppressor cells (MDSCs) in the lung of C57BL/6j (B6) mice pretreated with tumor exosomes. These effects were blunted when MyD88 knockout (KO) mice were pretreated with tumor exosomes. MDSCs induced by tumor exosomes and isolated from wild-type B6 mice also more potently inhibited T cell activation and induction of interleukin-6 and tumor necrosis factor-α than MDSCs isolated from the lung of MyD88 KO mice. In vitro, addition of tumor exosomes to bone marrow-derived CD11b+ Gr-1+ cells isolated from wild-type B6 mice resulted in more cytokine production, including tumor necrosis factor-α, interleukin-6, and the chemokine CCL2, than CD11b +Gr-1+ cells isolated from MyD88 KO mice. Moreover, lower levels of CCL2 were observed in the lungs in MyD88 KO mice pretreated with tumor exosomes than that in wild-type mice. Together these data demonstrate a pivotal role for MyD88 in tumor exosome-mediated expansion of MDSCs and tumor metastasis. Copyright © American Society for Investigative Pathology.

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