The Cross-Talk between miR-511-3p and C-Type Lectin Receptors on Dendritic Cells Affects Dendritic Cell Function.

MicroRNAs are small, noncoding RNAs that function as posttranscriptional modulators of gene expression by binding target mRNAs and inhibiting translation. They are therefore crucial regulators of several biological as well as immunological events. Recently, miR-511-3p has been implicated in the development and differentiation of APCs, such as dendritic cells (DCs), and regulating several human diseases. Interestingly, miR-511-3p is embedded within the human MRC1 gene that encodes the mannose receptor. In this study, we sought to examine the impact of miR-511-3p up- or downregulation on human DC surface phenotype, cytokine profile, immunogenicity (using IDO activity as a surrogate), and downstream T cell polarization. Using gene silencing and a selection of microRNA mimics, we could successfully suppress or induce the expression of miR-511-3p in DCs. Consequently, we show for the first time, to our knowledge, that inhibition and/or overexpression of miR-511-3p has opposing effects on the expression levels of two key C-type lectin receptors, namely the mannose receptor and DC-specific ICAM 3 nonintegrin at protein and mRNA levels, thereby affecting C-type lectin receptor-induced modulation of IDO activity in DCs. Furthermore, we show that downregulation of miR-511-3p drives an anti-inflammatory DC response characterized by IL-10 production. Interestingly, the miR-511-3plow DCs also promoted IL-4 secretion and suppressed IL-17 in cocultures with autologous T cells. Together, our data highlight the potential role of miR-511 in regulating DC function and downstream events leading to Th polarization and immune modulation.

Report: Unsupervised identification of malaria parasites using computer vision.

Malaria in human is a serious and fatal tropical disease. This disease results from Anopheles mosquitoes that are infected by Plasmodium species. The clinical diagnosis of malaria based on the history, symptoms and clinical findings must always be confirmed by laboratory diagnosis. Laboratory diagnosis of malaria involves identification of malaria parasite or its antigen / products in the blood of the patient. Manual diagnosis of malaria parasite by the pathologists has proven to become cumbersome. Therefore, there is a need of automatic, efficient and accurate identification of malaria parasite. In this paper, we proposed a computer vision based approach to identify the malaria parasite from light microscopy images. This research deals with the challenges involved in the automatic detection of malaria parasite tissues. Our proposed method is based on the pixel-based approach. We used K-means clustering (unsupervised approach) for the segmentation to identify malaria parasite tissues.

Mineralizing Coating on 3D Printed Scaffolds for the Promotion of Osseointegration.

Design and fabrication of implants that can perform better than autologous bone grafts remain an unmet challenge for the hard tissue regeneration in craniomaxillofacial applications. Here, we report an integrated approach combining additive manufacturing with supramolecular chemistry to develop acellular mineralizing 3D printed scaffolds for hard tissue regeneration. Our approach relies on an elastin-like recombinamer (ELR) coating designed to trigger and guide the growth of ordered apatite on the surface of 3D printed nylon scaffolds. Three test samples including a) uncoated nylon scaffolds (referred to as "Uncoated"), b) ELR coated scaffolds (referred to as "ELR only"), and c) ELR coated and in vitro mineralized scaffolds (referred to as "Pre-mineralized") were prepared and tested for in vitro and in vivo performance. All test samples supported normal human immortalized mesenchymal stem cell adhesion, growth, and differentiation with enhanced cell proliferation observed in the "Pre-mineralized" samples. Using a rabbit calvarial in vivo model, 'Pre-mineralized' scaffolds also exhibited higher bone ingrowth into scaffold pores and cavities with higher tissue-implant integration. However, the coated scaffolds ("ELR only" and "Pre-mineralized") did not exhibit significantly more new bone formation compared to "Uncoated" scaffolds. Overall, the mineralizing coating offers an opportunity to enhance integration of 3D printed bone implants. However, there is a need to further decipher and tune their immunologic response to develop truly osteoinductive/conductive surfaces.

Microparticles Decorated with Cell-Instructive Surface Chemistries Actively Promote Wound Healing.

Wound healing is a complex biological process involving close crosstalk between various cell types. Dysregulation in any of these processes, such as in diabetic wounds, results in chronic nonhealing wounds. Fibroblasts are a critical cell type involved in the formation of granulation tissue, essential for effective wound healing. 315 different polymer surfaces are screened to identify candidates which actively drive fibroblasts toward either pro- or antiproliferative functional phenotypes. Fibroblast-instructive chemistries are identified, which are synthesized into surfactants to fabricate easy to administer microparticles for direct application to diabetic wounds. The pro-proliferative microfluidic derived particles are able to successfully promote neovascularization, granulation tissue formation, and wound closure after a single application to the wound bed. These active novel bio-instructive microparticles show great potential as a route to reducing the burden of chronic wounds.