Latest Results The latest content available from Springer http://fionamettini.com Latest Results http://fionamettini.com/10.1007/978-3-030-44921-6 2021-01-01 10.1007/978-3-030-44921-6 Latest Results http://fionamettini.com/11480 2021-01-01 11480 Latest Results http://fionamettini.com/10.1007/978-1-0716-0916-3 2021-01-01 10.1007/978-1-0716-0916-3 Latest Results http://fionamettini.com/10.1007/978-3-030-44925-4 2021-01-01 10.1007/978-3-030-44925-4 Latest Results http://fionamettini.com/7651 2021-01-01 7651 Latest Results <h3 class="a-plus-plus">Abstract</h3> <p class="a-plus-plus">Xenograft models allow for an in vivo approach to monitor cellular functions within the context of a host microenvironment. Here we describe a protocol to generate a xenograft model of venous malformation (VM) based on the use of human umbilical vein endothelial cells (HUVEC) expressing a constitutive active form of the endothelial tyrosine kinase receptor TEK (TIE2 p.L914F) or patient-derived EC containing TIE2 and/or PIK3CA gene mutations. Hyperactive somatic <em class="a-plus-plus">TIE2</em> and <em class="a-plus-plus">PIK3CA</em> mutations are a common hallmark of VM in patient lesions. The EC are injected subcutaneously on the back of athymic nude mice to generate ectatic vascular channels and recapitulate histopathological features of VM patient tissue histology. Lesion plugs with TIE2/PIK3CA-mutant EC are visibly vascularized within 7–9 days of subcutaneous injection, making this a great tool to study venous malformation.</p> http://fionamettini.com/10.1007/978-1-0716-0916-3_13 2021-01-01 10.1007/978-1-0716-0916-3_13 Latest Results <h3 class="a-plus-plus">Abstract</h3> <p class="a-plus-plus">Several studies are available addressing the mechanisms of vascular morphogenesis in order to unravel how cooperative cell behavior can follow from the underlying, genetically regulated behavior of endothelial cells and from cell-to-cell and cell-to-extracellular matrix interactions. From the morphological standpoint several aspects of the process are of interest. They include the way the pattern of vessels fills the available tissue space and how the network grows during the angiogenic process, namely how a main trunk divides into smaller branches, and how branching occurs at different distances from the root point of a vascular tree. A third morphological aspect of interest concerns the spatial relationship between vessels and tissue cells able to secrete factors modulating endothelial cells self-organization, thus influencing vascular rearrangement.</p> <p class="a-plus-plus">In the present chapter image analysis methods allowing for a quantitative characterization of these morphological aspects will be detailed and discussed. They are almost based on concepts derived from the theoretical framework represented by spatial statistics.</p> http://fionamettini.com/10.1007/978-1-0716-0916-3_7 2021-01-01 10.1007/978-1-0716-0916-3_7 Latest Results <h3 class="a-plus-plus">Abstract</h3> <p class="a-plus-plus">The zebrafish has emerged as a valuable and important model organism for studying vascular development and vascular biology. Here, we discuss some of the approaches used to study vessels in fish, including loss-of-function tools such as morpholinos and genetic mutants, along with methods and considerations for assessing vascular phenotypes. We also provide detailed protocols for methods used for vital imaging of the zebrafish vasculature, including microangiography and long-term time-lapse imaging. The methods we describe, and the considerations we suggest using for assessing phenotypes observed using these methods, will help ensure reliable, valid conclusions when assessing vascular phenotypes following genetic or experimental manipulation of zebrafish.</p> http://fionamettini.com/10.1007/978-1-0716-0916-3_15 2021-01-01 10.1007/978-1-0716-0916-3_15 Latest Results <h3 class="a-plus-plus">Abstract</h3> <p class="a-plus-plus">For more than 2000 years, the avian embryo has helped scientists understand questions of developmental and cell biology. As early as 350 BC Aristotle described embryonic development inside a chicken egg (<span class="a-plus-plus emphasis fontcategory-sans-serif">Aristotle, Generation of animals. Loeb Classical Library (translated), vol. 8, 1943</span>). In the seventeenth century, Marcello Malpighi, referred to as the father of embryology, first diagramed the microscopic morphogenesis of the chick embryo, including extensive characterization of the cardiovascular system (<span class="a-plus-plus emphasis fontcategory-sans-serif">Pearce Eur Neurol 58(4):253–255, 2007; West, Am J Physiol Lung Cell Mol Physiol 304(6):L383–L390, 2016</span>). The ease of accessibility to the embryo and similarity to mammalian development have made avians a powerful system among model organisms. Currently, a unique combination of classical and modern techniques is employed for investigation of the vascular system in the avian embryo. Here, we will introduce the essential techniques of embryonic manipulation for experimental study in vascular biology.</p> http://fionamettini.com/10.1007/978-1-0716-0916-3_9 2021-01-01 10.1007/978-1-0716-0916-3_9 Latest Results <h3 class="a-plus-plus">Abstract</h3> <p class="a-plus-plus">Nanotechnology became a widespread technology in recent years in several medical and pharmaceutical applications. Drug-delivery systems based on nanoparticle technologies have the prospective industrial revolution that could be considered as a landmark of future pharmaceutical industries. The major goals in designing nanoparticles as a delivery system include enhancing bioavailability by enhancing solubility and dissolution rate, targeting the drug to specific organs, and controlling drug release rate. Some other nanoparticles illustrate vast promise in the field of tumor imaging and the early identification of malignant tissue such as fluorescent polymeric nanoparticles. The chapter discusses different classes of pharmaceutical nanoparticles including nanonized drug (API) particles, biodegradable polymeric nanoparticles, and hydrophobic nanoparticles. The nanonized drug (API) particles are mostly applied for enhancing drug solubility and dissolution rate, which, in turn, can improve its bioavailability. These nanosized drugs (API) particles are prepared by either top-down or bottom-up techniques. In addition, the chapter also spots the light on variable polymer classes utilized in polymeric nanoparticles, including hydrophilic, hydrophobic, and biodegradable polymers. Furthermore, different manufacturing techniques adopted for the production of polymeric nanoparticles based on the type of the polymers were described. Also, the nanonization techniques of the polymeric nanoparticles are based on physical methods including primary and multiple emulsion solvent evaporation methods, ionic gelation, spray-drying, supercritical fluid technology, as well as precipitation with a compressed fluid techniques anti-solvent were clarified. Other polymeric nanoparticle manufacturing techniques are based on chemical synthesis schemes such as silica nanoparticles of variable internal structures. Furthermore, the polymeric nanoparticles as targeting system are not only for healthy cells but also diseased cells. The applications of nanoparticles in drug delivery and targeting, focusing the conventional and recent methods of preparation, were briefly specified. At the end of this chapter, final remarks and recommendations on the optimal methods of manufacturing techniques are suggested.</p> http://fionamettini.com/10.1007/978-3-030-44925-4_2 2021-01-01 10.1007/978-3-030-44925-4_2 Latest Results <h3 class="a-plus-plus">Abstract</h3> <p class="a-plus-plus">Cancer is a group of around 100 diseases that has been tormenting mankind since ancient time. Due to cancer, estimated 8.2 million people died globally in 2012, and the toll is expected to reach 13 million in 2030. Despite the improvement of conventional therapeutic modalities, the outcome of cancer patients has not improved significantly. So, alternative therapeutic modalities and new effective anticancer drugs are highly sought for. Different parts of plants and their extracts have been used to cure many diseases and relive from physical agony since ancient times. In the traditional system of medicine, herbal products have been used for treating different types of diseases and alignments globally. Active compounds from herbal medicine, such as curcumin, are found to be effective against cancer. Despite their excellent therapeutic ability, the potential of these herbal compounds or phytochemicals is limited due to their low water solubility and poor bioavailability.</p> <p class="a-plus-plus">Advances in nanomedicines are revolutionizing the healthcare sector. Significant progresses have been made in development of nanocarriers in recent decades. Therapeutic efficacies of conventional drugs are reported to enhance by many folds using these novel nanocarriers through the intervention of nanotechnology. Application of nanotechnology may be effective in overcoming limitations of herbal drugs such as low water solubility, poor bioavailability, toxicity, and poor therapeutic efficacy of the drugs. It greatly helps in achieving higher efficiency of the drugs compared to its molecular form. Development of herbal-based nanocarriers like polymeric nanoparticles, dendrimers, liposomes, and micelles is reported to be more effective in treatment and managements of cancer. Loading of herbal compounds within these nanodrug delivery systems changes their pharmacokinetics profile and increases their bioavailability and therapeutic efficacy.</p> <p class="a-plus-plus">In this review, a comprehensive effort has been made on discovery of herbal drugs, herbal nanocarriers, and their application for cancer therapy. The coverage of this review will also extend to its current status and future prospects with elaborative and graphical examples.</p> http://fionamettini.com/10.1007/978-3-030-44921-6_2 2021-01-01 10.1007/978-3-030-44921-6_2 Latest Results <h3 class="a-plus-plus">Abstract</h3> <p class="a-plus-plus">Nanopharmaceuticals are systems in which therapeutic drug delivery works at the nanoscale. Even though several such systems are developed, most of them possess significant drawbacks. Some noted drawbacks include immunogenicity, cytotoxicity, accessibility to the target tissue, in vivo stability, biocompatibility, and effort in synthesizing procedure composed of complicated chemical reactions or techniques. Therefore, studies concerned with the fabrication of nanostructures based on biomolecules gained wide interest. The unique characteristics of biomolecules like DNA enable them to self-assemble and develop into variable nanostructures having tremendous applications. In this review, we focus on nanostructures fabricated from DNA. Their biocompatibility, structural stability, and unique recognition sites make them most suitable building blocks for the development of smart nanostructures. The first DNA-based nanostructure was a stick cube with a motif-based design. Incorporation of materials like polymers, development of newer technique like DNA origami, and the possibility of further modifications in the developed structures enable its high utility. In this review, we discuss concepts and applications of DNA nanostructures, DNA–polymer assembly, DNA origami technique, and structural modifications of DNA nanostructures.</p> http://fionamettini.com/10.1007/978-3-030-44925-4_4 2021-01-01 10.1007/978-3-030-44925-4_4 Latest Results <h3 class="a-plus-plus">Abstract</h3> <p class="a-plus-plus">Drug discovery has faced many challenges, and the diversity of natural products offers a huge number of opportunities for new drug findings. Most of the potential candidates result from plants since plants have several and interesting biological activities. However, the <em class="a-plus-plus">in vivo</em> efficacy of such candidates is frequently limited due to their low absorption. Thus, enhancing the bioavailability of natural products through the improvement of their pharmacokinetic and biodistribution features, as well as their targeting efficacy, is a crucial step in the development of new therapeutic strategies.</p> <p class="a-plus-plus">Here, we reviewed nanotechnology as a rising approach for drug delivery, presenting smart nanocarriers that can selectively deliver appropriate levels of a therapeutic agent. Moreover, in order to deliver the therapeutic agent to target cells, nanocarriers can also be efficient targeting systems. Another benefit here discussed in the use of nanocarriers to deliver natural products is the controlled drug release.</p> <p class="a-plus-plus">This review describes many types of nanocarriers with structural and functional differences between them which can be chosen accordingly to the encapsulated drug characteristics, to the specific target, or even to the desired release rate. With regard to natural products, we highlight several natural products that are already being commercialized or in clinical study phase with impressive therapeutic improvements using these nanocarriers. On the other hand, there are also a large number of natural products that are being used as encapsulant material in pioneering nanocarriers. This review aims to summarize the development in several key areas relevant to natural products in nanopharmaceuticals. Besides the potential beneficial use, also attention is drawn to the question how we should proceed with the safety and efficacy evaluation of the nanopharmaceuticals for natural product delivery. Nonetheless, research into sophisticated, science-driven solutions is still continuing; expectations related to therapeutic efficacy are high to meet clinical needs, but the progress made has been noticeable.</p> http://fionamettini.com/10.1007/978-3-030-44921-6_4 2021-01-01 10.1007/978-3-030-44921-6_4 Latest Results <h3 class="a-plus-plus">Abstract</h3> <p class="a-plus-plus">Background: The delivery of drugs or actives through the skin provides a convenient route of administration because it is noninvasive and can typically be self-administered. In skin delivery, different strategies have been developed to enhance the rate and extent of drug transport across the skin. These strategies consist in particulate carriers such as nanoparticles generally made of polymers and lipids where some advantages are solubility improvement of poorly water-soluble drugs, increase of skin permeation through different mechanisms, and ability to modify drug pharmacokinetics. Besides polymeric- and lipidic-, metallic-based nanoparticles like silver nanoparticles are recently used as nanocarriers for skin delivery due to their strong and broad-spectrum antimicrobial characteristics. All encapsulant materials (polymers, lipids, and metals) and solvents used in the drug delivery are approved by Food and Drug Administration (FDA) and European Medicines Agency (EMA) (as biocompatible and biodegradable materials). Major advances: In this chapter, a compilation of the type and the therapeutic implications of nanotechnology applied to the skin in pharmaceutical area as well as safety issues, ecotoxicity concerns, and regulatory framework of different nanoparticles for skin delivery over the last 40 years was described.</p> http://fionamettini.com/10.1007/978-3-030-44925-4_6 2021-01-01 10.1007/978-3-030-44925-4_6 Latest Results <h3 class="a-plus-plus">Abstract</h3> <p class="a-plus-plus">Recently dietary and plant-derived phytochemicals are rising into limelight as many people developed a propensity towards opting nature-dependent healthy lifestyle. Scientific advancements highlight the effectiveness of phytochemicals in the treatment of many diseases and for various lifestyle benefits. Traditionally used in medicines, food supplements, and cosmeceutical products, phytochemical compounds are now conjoined with modern science to produce significant health benefits to humans as they possess fiddling risks compared to synthetic chemical entities. Phytochemicals are implemented in different forms and for different purposes such as phyto-, aroma-, and gemmotherapy for their potential health benefits. But the formulation of these phytochemicals for various applications is a major concern primarily owing to their low bioavailability, solubility, and the need to be taken in combination or as whole food. Hence, efficient delivery systems such as nano-engineered formulations are imperative to potentially yield the complete benefits from these phytochemicals. Besides enhancing the solubility and stability of phytochemicals, the nano-delivery systems can also prolong their average blood circulation time. Consequently, the high differential uptake efficiency, enhanced permeation, and retention characteristics in target tissues could prevent phytochemicals from premature interaction with the biological environment, thus resulting in decreased toxicity and favorable dose optimization possibilities. These advanced delivery systems also aid in the targeted delivery approaches. This chapter depicts the major natural products employed for the human benefits, their limitations, and nanotechnological solutions to triumph these limitations.</p> http://fionamettini.com/10.1007/978-3-030-44921-6_6 2021-01-01 10.1007/978-3-030-44921-6_6 Latest Results <h3 class="a-plus-plus">Abstract</h3> <p class="a-plus-plus">Conventional drug discovery and screening processes have important drawbacks particularly in preclinical phase which include in vitro drug screening test, namely, 2D cell culture, and in vivo test on animal models. It is known that 2D cell cultures are insufficient to indicate drug response of real tissues and organs. Animal models also mislead about drug response with the same reason, and there are some ethical issues about animal models as well. These drawbacks lead to failure of drug candidate at later phases or after approved by the Food and Drug Administration (FDA). Since the drug development phases are very costly processes, this failure means time and money consumption to drug companies. More importantly if the drug fails after approval, many patients will be exposed and be affected by its side effects.</p> <p class="a-plus-plus">Recently, three-dimensional (3D) cell culture systems have been started to be used in drug discovery and development in order to develop more realistic and more predictive models for in vivo tests. Advances in tissue engineering, cell biology, biomaterials, microfabrication, and microfluidic technologies have enabled to mimic the functions of varied tissues and organs on a single chip. Recent developments in microfabrication techniques lead to more precise fabrication of microfluidic chips that provides miniaturization of the conventional process. It also leads to development of cell-based high-throughput screening (HTS) platforms that are known as “organ-on-a-chip” systems. Currently, organ-on-a-chip technologies are the most promising experimental platforms to reduce animal tests and to improve the efficiency of preclinical prediction of drugs. Compared to conventional systems, these platforms are used to reduce sample volume. Besides, combination of 3D cell culture with microfluidic platform makes it possible to mimic biochemical and biomechanical microenvironment of real tissues. In other words, more physiologically relevant and realistic models can be created. This potential use of microfluidic systems in drug discovery has created their own market which is estimated to reach $3.6–5.7 billion by 2018, and drug discovery is the second largest market area in microfluidic applications. In this manuscript on-chip drug screening models were reviewed which aim to improve drug discovery and development. On-chip drug screening studies from the nanopharmaceutical point of view were reviewed under the following sections: (1) microfabrication of microfluidics; (2) utilization of microfluidics for drug screening, in particular organ-on-a-chip drug screening technologies; and (3) commercialization, marketing, and challenges of microfluidic drug screening platforms.</p> http://fionamettini.com/10.1007/978-3-030-44925-4_8 2021-01-01 10.1007/978-3-030-44925-4_8 Latest Results <h3 class="a-plus-plus">Abstract</h3> <p class="a-plus-plus">Nanopharmaceuticals are an emerging innovative domain of research that integrates nanotechnology and biotechnology applications. This technological development will permit producing unique nanopharmaceutical compounds used in the medical field, particularly in drug delivery. This book chapter focuses on organic (polymeric and lipid nanoparticles, dendrimers) and inorganic (magnetic nanoparticles and quantum dots) materials used to produce nanopharmaceuticals with different characteristics such as size, structure, chemical composition, and behavior enabling their use in different fields, one of which the drug delivery systems. Within drug delivery systems, special emphasis is given to vesicular (liposomes) and nanoparticulate carriers as they are the most explored at the market level. The biotechnological development, main features, and examples of applications of some types of nanostructures are discussed. Moreover, data available on sources, pathways, and effects of nanopharmaceuticals in the aquatic environment are discussed, with special emphasis on the environmental impact of these nanopharmaceuticals to the aquatic environment. Results indicate that there is no standard protocol for ecotoxicological testing and limited information exists on environmental impact assessment of nanopharmaceuticals. Thus, human and environmental safety guidelines are urgently needed to protect both the human health and the environment.</p> http://fionamettini.com/10.1007/978-3-030-44921-6_8 2021-01-01 10.1007/978-3-030-44921-6_8 Latest Results <h3 class="a-plus-plus">Abstract</h3> <p class="a-plus-plus">Judah Folkman (1933–2008) made seminal discoveries on the mechanisms of angiogenesis which have opened a field of investigation worldwide. This chapter summarizes the fundamental contribution of Folkman in the setting of angiogenesis assays in vivo and in vitro.</p> http://fionamettini.com/10.1007/978-1-0716-0916-3_2 2021-01-01 10.1007/978-1-0716-0916-3_2 Latest Results <h3 class="a-plus-plus">Abstract</h3> <p class="a-plus-plus">Dynamic imaging is a powerful approach to assess the function of a developing organ system. The heart is a dynamic organ that undergoes quick morphological and mechanical changes through early embryonic development. Defining the embyonic mouse heart's normal function is important for our own understanding of human heart development and will inform us on treatments and prevention of congenital heart defects (CHD). Traditional methods such as ultrasound or fluorescence-based microscopy are suitable for live dynamic imaging, are excellent to visualize structure and connect gene expression to phenotypes, but can be of low quality in resolving fine features and lack imaging depth and scale to fully appreciate organ morphogenesis. Additionally, previous methods can be limited in accommodating a live imaging apparatus capable of sustaining whole embryo development for extended periods time. Optical coherence tomography (OCT) is unique in this circumstance because acquisition of three-dimensional images without contrast reagents, at single cell resolution make it a suitable modality to visualize fine structures in the developing embryo. OCT setups are highly customizable for live imaging because of the tethered imaging arm, due to its setup as a fiber-based interferometer. OCT allows for 4D (3D + time) functional imaging of living mouse embryos and can provide functional and mechanical information to ascertain how the heart’s pump function changes through development. In this chapter, we will focus on how we use OCT to visualize live heart dynamics at different stages of development and provide mechanical information to reveal functional properties of the developing heart.</p> http://fionamettini.com/10.1007/978-1-0716-0916-3_10 2021-01-01 10.1007/978-1-0716-0916-3_10 Latest Results <h3 class="a-plus-plus">Abstract</h3> <p class="a-plus-plus">During angiogenesis, endothelial cells must undergo a coordinated set of morphological changes in order to form a new vessel. There is a need for endothelial cells to communicate with each other in order to take up different identities in the sprout and to migrate collectively as a connected chord. Endothelial cells must also interact with a wide range of other cells that contribute to vessel formation. In ischemic disease, hypoxic cells in tissue will generate proangiogenic signals that promote and guide angiogenesis. In solid tumors, this function is co-opted by tumor cells, which make a complex range of interactions with endothelial cells, even integrating into the walls of vessels. In vessel repair, cells from the immune system contribute to the promotion and remodeling of new vessels. The coculture angiogenesis assay is a long-term in vitro protocol that uses fibroblasts to secrete and condition an artificial stromal matrix for tubules to grow through. We show here how the assay can be easily adapted to include additional cell types, facilitating the study of cellular interactions during neovascularization.</p> http://fionamettini.com/10.1007/978-1-0716-0916-3_4 2021-01-01 10.1007/978-1-0716-0916-3_4