Current Drug Targets - Volume 20, Issue 8, 2019

By interconnecting nanomachines and forming nanonetworks, the capacities of single nanomachines are expected to be enhanced, as the ensuing information exchange will allow them to cooperate towards a common goal. Nowadays, systems normally use electromagnetic signals to encode, send and receive information, however, in a novel communication paradigm, molecular transceivers, channel models or protocols use molecules. This article presents the current developments in nanomachines along with their future architecture to better understand nanonetwork scenarios in biomedical applications. Furthermore, to highlight the communication needs between nanomachines, two applications for nanonetworks are also presented: i) a new networking paradigm, called the Internet of NanoThings, that allows nanoscale devices to interconnect with existing communication networks, and ii) Molecular Communication, where the propagation of chemical compounds like drug particles, carry out the information exchange.

In this mini-review, we highlight the potential of the biopolymer bacterial cellulose to treat damaged epithelial tissues. Epithelial tissues are cell sheets that delimitate both the external body surfaces and the internal cavities and organs. Epithelia serve as physical protection to underlying organs, regulate the diffusion of molecules and ions, secrete substances and filtrate body fluids, among other vital functions. Because of their continuous exposure to environmental stressors, damage to epithelial tissues is highly prevalent. Here, we first compare the properties of bacterial cellulose to the current gold standard, collagen, and then we examine the use of bacterial cellulose patches to heal specific epithelial tissues; the outer skin, the ocular surface, the oral mucosa and other epithelial surfaces. Special emphasis is made on the dermis since, to date, this is the most widespread medical use of bacterial cellulose. It is important to note that some epithelial tissues represent only the outermost layer of more complex structures such as the skin or the cornea. In these situations, depending on the penetration of the lesion, bacterial cellulose might also be involved in the regeneration of, for instance, inner connective tissue.

With the advent of inexpensive and highly accurate 3D printing devices, a tremendous flurry of research activity has been unleashed into new resorbable, polymeric materials that can be printed using three approaches: hydrogels for bioprinting and bioplotting, sintered polymer powders, and solid cured (photocrosslinked) resins. Additionally, there is a race to understand the role of extracellular matrix components and cell signalling molecules and to fashion ways to incorporate these materials into resorbable implants. These chimeric materials along with microfluidic devices to study organs or create labs on chips, are all receiving intense attention despite the limited number of polymer systems that can accommodate the biofabrication processes necessary to render these constructs. Perhaps most telling is the limited number of photo-crosslinkable, resorbable polymers and fabrication additives (e.g., photoinitiators, solvents, dyes, dispersants, emulsifiers, or bioactive molecules such as micro-RNAs, peptides, proteins, exosomes, micelles, or ceramic crystals) available to create resins that have been validated as biocompatible. Advances are needed to manipulate 4D properties of 3D printed scaffolds such as pre-implantation cell culture, mechanical properties, resorption kinetics, drug delivery, scaffold surface functionalization, cell attachment, cell proliferation, cell maturation, or tissue remodelling; all of which are necessary for regenerative medicine applications along with expanding the small set of materials in clinical use. This manuscript presents a review of the foundation of the most common photopolymerizable resins for solidcured scaffolds and medical devices, namely, polyethylene glycol (PEG), poly(D, L-lactide) (PDLLA), poly--caprolactone (PCL), and poly(propylene fumarate) (PPF), along with methodological advances for 3D Printing tissue engineered implants (e.g., via stereolithography [SLA], continuous Digital Light Processing [cDLP], and Liquid Crystal Display [LCD]).

Breast Cancer (BC) is the most common cancer among women and the second cause of female death for cancer. When the tumor is not correctly eradicated, there is a high relapse risk and incidence of metastasis. Breast Cancer Stem Cells (BCSCs) are responsible for initiating tumors and are resistant to current anticancer therapies being in part responsible for tumor relapse and metastasis. The study of BCSCs is limited due to their low percentage within both tumors and established cell models. Hence, three-dimensional (3D) supports are presented as an interesting tool to keep the stem-like features in 3D cell culture. In this review, several 3D culture systems are discussed. Moreover, scaffolds are presented as a tool to enrich in BCSCs in order to find new specific therapeutic strategies against this malignant subpopulation. Anticancer treatments focused on BCSCs could be useful for BC patients, with particular interest in those that progress to current therapies.

Fibroblast growth factors (FGFs) are pleiotropic molecules exerting autocrine, intracrine and paracrine functions via activating four tyrosine kinase FGF receptors (FGFR), which further trigger a variety of cellular processes including angiogenesis, evasion from apoptosis, bone formation, embryogenesis, wound repair and homeostasis. Four major mechanisms including angiogenesis, inflammation, cell proliferation, and metastasis are active in FGF/FGFR-driven tumors. Furthermore, gain-of-function or loss-of-function in FGFRs1-4 which is due to amplification, fusions, mutations, and changes in tumor–stromal cells interactions, is associated with the development and progression of cancer. Although, the developed small molecule or antibodies targeting FGFR signaling offer immense potential for cancer therapy, emergence of drug resistance, activation of compensatory pathways and systemic toxicity of modulators are bottlenecks in clinical application of anti-FGFRs. In this review, we present FGF/FGFR structure and the mechanisms of its function, as well as cross-talks with other nodes and/or signaling pathways. We describe deregulation of FGF/FGFR-related mechanisms in human disease and tumor progression leading to the presentation of emerging therapeutic approaches, resistance to FGFR targeting, and clinical potentials of individual FGF family in several human cancers. Additionally, the underlying biological mechanisms of FGF/FGFR signaling, besides several attempts to develop predictive biomarkers and combination therapies for different cancers have been explored.

Vitamin A and its derivatives (retinoids) act as potent regulators in many aspects of mammalian reproduction, development, repair, and maintenance of differentiated tissue functioning. Unlike other vitamins, Vitamin A and retinoids, which have hormonal actions, present significant toxicity, which plays roles in clinically relevant situations, such as hypervitaminosis A and retinoic acid ("differentiation") syndrome. Although clinical presentation is conspicuous in states of insufficient or excessive Vitamin A and retinoid concentration, equally relevant effects on host resistance to specific infectious agents, and in the general maintenance of immune homeostasis, may go unnoticed, because their expression requires either pathogen exposure or the presence of inflammatory co-morbidities. There is a vast literature on the roles played by retinoids in the maintenance of a tolerogenic, noninflammatory environment in the gut mucosa, which is considered by many investigators representative of a general role played by retinoids as anti-inflammatory hormones elsewhere. However, in the gut mucosa itself, as well as in the bone marrow and inflammatory sites, context determines whether one observes an anti-inflammatory or proinflammatory action of retinoids. Both interactions between specialized cell populations, and interactions between retinoids and other classes of mediators/regulators, such as cytokines and glucocorticoid hormones, must be considered as important factors contributing to this overall context. We review evidence from recent studies on mucosal immunity, granulocyte biology and respiratory allergy models, highlighting the relevance of these variables as well as their possible contributions to the observed outcomes.

Newer classes of medications have been proven useful in glycemic control in type 2 diabetes (T2D), but many do not appear capable to slow down the progressive loss of ß-cell function, or to improve population-level glycemic control. Positive energy balance, e.g. surplus energy intake over expenditure, is at the core for developing metabolic syndrome and T2D. Currently available glycemic control drugs come to the market based on their 1-2 years risk-benefit profiles, but most of them do not correct positive energy balance and lose efficacy in the long-term. This denouement is destined by a positive energy balance of T2D. There is continuous endeavor/investment in new drugs for T2D. In this review, we compared the effects of commonly used oral hypoglycemic agents on energy balance and discussed several novel therapeutic targets/approaches for T2D that could potentially correct positive energy balance: changing the composition of intestinal host-microbiota to alleviate excess caloric consumption, controlling chylomicron uptake into intestinal lacteals to reduce excessive caloric intake, and activating pyruvate kinase M2 (PKM2) to ameliorate glucose metabolism and increase energy expenditure. We further reviewed how nicotine affects body weight and ameliorates positive energy balance, and ways to encourage people to adopt a more healthy lifestyle by exercising more and/or decreasing caloric intake. These potential targets/approaches may hopefully correct positive energy balance, delay disease progression, reverse some pathophysiological changes, and eventually prevent and/or cure the disease. Drug development strategies applying new insights into T2D process and therapeutic index to correct positive energy balance need to be seriously considered.