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Biomicrofluidics Jul 2020Organ-on-a-chip (OOC) is a very ambitious emerging technology with a high potential to revolutionize many medical and industrial sectors, particularly in... (Review)
Review
Organ-on-a-chip (OOC) is a very ambitious emerging technology with a high potential to revolutionize many medical and industrial sectors, particularly in preclinical-to-clinical translation in the pharmaceutical arena. , the function of the organ(s) is orchestrated by a complex cellular structure and physiochemical factors within the extracellular matrix and secreted by various types of cells. The trend in modeling is to simplify the complex anatomy of the human organ(s) to the minimal essential cellular structure "micro-anatomy" instead of recapitulating the full cellular milieu that enables studying the absorption, metabolism, as well as the mechanistic investigation of drug compounds in a "systemic manner." However, in order to reflect the human physiology and hence to be able to bridge the gap between the and data, simplification should not compromise the physiological relevance. Engineering principles have long been applied to solve medical challenges, and at this stage of organ-on-a-chip technology development, the work of biomedical engineers, focusing on device engineering, is more important than ever to accelerate the technology transfer from the academic lab bench to specialized product development institutions and to the increasingly demanding market. In this paper, instead of presenting a narrative review of the literature, we systemically present a synthesis of the best available organ-on-a-chip technology from what is found, what has been achieved, and what yet needs to be done. We emphasized mainly on the requirements of a "good model that meets the industrial need" in terms of the structure (micro-anatomy), functions (micro-physiology), and characteristics of the device that hosts the biological model. Finally, we discuss the biological model-device integration supported by an example and the major challenges that delay the OOC technology transfer to the industry and recommended possible options to realize a functional organ-on-a-chip system.
PubMed: 32699563
DOI: 10.1063/5.0011583 -
Entropy (Basel, Switzerland) Nov 2020Self-organization in nonequilibrium systems has been known for over 50 years. Under nonequilibrium conditions, the state of a system can become unstable and a transition...
Self-organization in nonequilibrium systems has been known for over 50 years. Under nonequilibrium conditions, the state of a system can become unstable and a transition to an organized structure can occur. Such structures include oscillating chemical reactions and spatiotemporal patterns in chemical and other systems. Because entropy and free-energy dissipating irreversible processes generate and maintain these structures, these have been called dissipative structures. Our recent research revealed that some of these structures exhibit organism-like behavior, reinforcing the earlier expectation that the study of dissipative structures will provide insights into the nature of organisms and their origin. In this article, we summarize our study of organism-like behavior in electrically and chemically driven systems. The highly complex behavior of these systems shows the time evolution to states of higher entropy production. Using these systems as an example, we present some concepts that give us an understanding of biological organisms and their evolution.
PubMed: 33287069
DOI: 10.3390/e22111305 -
Hellenic Journal of Nuclear Medicine 2023Personalized dosimetry is tending to become the "gold standard" in Molecular Radiotherapy (MRT). Setting up carefully all the procedures involved in the workflow is...
INTRODUCTION
Personalized dosimetry is tending to become the "gold standard" in Molecular Radiotherapy (MRT). Setting up carefully all the procedures involved in the workflow is crucial for the final clinical result.
AIM
Individualized MRT dosimetry using a recently installed commercial system, comprising of a dual SPECT/CT camera, a treatment planning software (TPS) and a dose calibrator was implemented on patients undergoing Lu-DOTATATE and Lu-PSMA therapies. The clinical workflow implemented in our department is presented in detail. Measurement and calculation of the Calibration Factor (CF) to translate the count rate into activity concentration (quantitative data), and system's commissioning, was discussed.
MATERIALS AND METHODS
Calibration of the dose calibrator, the SPECT/CT system and the TPS, measured using the clinical acquisition protocol, were analyzed along with potential errors introduced by the procedure and means of future optimization. In addition, image acquisition parameters, image reconstruction and image registration were discussed. Anatomical contouring of the organs at risk (OARs) and functional contouring of the lesions, followed by the dose calculation of the aforementioned structures, with the use of different calculation algorithms, were presented, compared and evaluated.
RESULTS AND DISCUSSION
According to our experience, different fitting of each organ's activity curve, results in differences in the final calculated dose. Use of bi-exponential fitting seems to better approach physical and metabolic decay. Calculated absorbed doses for the OARs were found similar to those expected from literature. Finally, department's future work was discussed, including reproducible patient setup for image acquisition, high dose CT for finer contouring and comparison of the calculated doses with other TPSs.
Topics: Humans; Radiometry; Single Photon Emission Computed Tomography Computed Tomography; Image Processing, Computer-Assisted; Radiotherapy Dosage; Algorithms
PubMed: 37658554
DOI: No ID Found -
Oncology Reports Apr 2021Environmental endocrine disruptor chemicals are substances that can alter the homeostasis of the endocrine system in living organisms. They can be released from several... (Review)
Review
Environmental endocrine disruptor chemicals are substances that can alter the homeostasis of the endocrine system in living organisms. They can be released from several products used in daily activities. Once in the organism, they can disrupt the endocrine function by mimicking or blocking naturally occurring hormones due to their similar chemical structure. This endocrine disruption is the most important cause of the well‑known hormone‑associate types of cancer. Additionally, it is decisive to determine the susceptibility of each organ to these compounds. Therefore, the present review aimed to summarize the effect of different environmental substances such as bisphenol A, dichlorodiphenyltrichloroethane and polychlorinated biphenyls in both the mammary and the prostate tissues. These organs were chosen due to their association with the hormonal system and their common features in carcinogenic mechanisms. Outcomes derived from the present review may provide evidence that should be considered in future debates regarding the effects of endocrine disruptors on carcinogenesis.
Topics: Animals; Benzhydryl Compounds; DDT; Endocrine Disruptors; Environmental Pollutants; Female; Humans; Male; Mammary Glands, Animal; Mammary Glands, Human; Phenols; Polychlorinated Biphenyls; Prostate
PubMed: 33649835
DOI: 10.3892/or.2021.7971 -
Frontiers in Cell and Developmental... 2017The long-term maintenance of an organism's homeostasis and health relies on the accurate regulation of organ-organ communication. Recently, there has been growing... (Review)
Review
The long-term maintenance of an organism's homeostasis and health relies on the accurate regulation of organ-organ communication. Recently, there has been growing interest in using the gastrointestinal tract to elucidate the regulatory programs that underlie the complex interactions between organs. Data obtained in this field have dramatically improved our understanding of how organ-organ communication contributes to the regulation of various aspects of the intestine, including its metabolic and physiological status. However, although research uncovering regulatory programs associated with interorgan communication has provided key insights, the underlying mechanisms have not been extensively explored. In this review, we highlight recent findings describing gut-neighbor and neighbor-neighbor communication models in adults and larvae, respectively, with a special focus on how a range of critical strategies concerning continuous interorgan communication and adjustment can be used to manipulate different aspects of biological processes. Given the high degree of similarity between the and mammalian intestinal epithelia, it can be anticipated that further analyses of the gastrointestinal tract will facilitate the discovery of similar mechanisms underlying organ-organ communication in other mammalian organs, such as the human intestine.
PubMed: 28421183
DOI: 10.3389/fcell.2017.00029 -
Frontiers in Psychology 2020The enactive and ecological approaches to embodied cognitive science are on a collision course. While both draw inspiration from similar views in psychology and... (Review)
Review
The enactive and ecological approaches to embodied cognitive science are on a collision course. While both draw inspiration from similar views in psychology and phenomenology, the two approaches initially held seemingly contradictory views and points of focus. Early enactivists saw value in the ecological approach but insisted that the two schools remain distinct. While ecological psychology challenged the common foes of mental representation and mind-body dualism, it seemingly did so at the cost of the autonomy of the agent. This is evidence that the early enactive and ecological approaches told different stories about how agents and environments interact. Whereas the enactive approach broadly focuses on agency and the organism's resilience to environmental perturbations, the ecological approach insists that organisms are best understood in terms of the organism-environment system and at the ecological scale. Historically, this tension created space for harsh criticisms from both sides and for some ecological psychologists to dismiss enactivism altogether. Despite their differences, both approaches use dynamic systems theory to explain the interactions between embodied agents and the environment or contextual milieu in which they are embedded. This has led some scholars to focus on the complementary elements of each approach and argue that the two schools are allies, thus rejecting the historical disagreements between the two approaches and calling for an ecological-enactive synthesis. The attempts to synthesize the approaches are noteworthy and should be considered steps in the right direction but are potentially problematic. If the two schools are merely synthesized to some form of ecological-enactivism, then something of value from both approaches could be lost. This is analogous to the hasty comparison between two seemingly similar schools of thought found in early attempts at East-West comparative philosophy. I argue that the relationship between the enactive and ecological approaches is both complementary and contrary and is thus best understood in terms of complementarity. Given the complexity of complementarity I will unpack the notion in steps. I will begin with the exploration of analogous concepts in Japanese Philosophy and gradually build a lens through which both agent environment and ecological enactive complementarities can be understood.
PubMed: 32903774
DOI: 10.3389/fpsyg.2020.01347 -
Integrative and Comparative Biology Dec 2023Motility is an essential factor for an organism's survival and diversification. With the advent of novel single-cell technologies, analytical frameworks, and theoretical... (Review)
Review
Motility is an essential factor for an organism's survival and diversification. With the advent of novel single-cell technologies, analytical frameworks, and theoretical methods, we can begin to probe the complex lives of microscopic motile organisms and answer the intertwining biological and physical questions of how these diverse lifeforms navigate their surroundings. Herein, we summarize the main mechanisms of microscale motility and give an overview of different experimental, analytical, and mathematical methods used to study them across different scales encompassing the molecular-, individual-, to population-level. We identify transferable techniques, pressing challenges, and future directions in the field. This review can serve as a starting point for researchers who are interested in exploring and quantifying the movements of organisms in the microscale world.
Topics: Animals; Movement; Single-Cell Analysis; Models, Theoretical; Cell Movement; Bacteria
PubMed: 37336589
DOI: 10.1093/icb/icad075 -
Disease Models & Mechanisms Mar 2016Many of the internal organ systems of Drosophila melanogaster are functionally analogous to those in vertebrates, including humans. Although humans and flies differ... (Review)
Review
Many of the internal organ systems of Drosophila melanogaster are functionally analogous to those in vertebrates, including humans. Although humans and flies differ greatly in terms of their gross morphological and cellular features, many of the molecular mechanisms that govern development and drive cellular and physiological processes are conserved between both organisms. The morphological differences are deceiving and have led researchers to undervalue the study of invertebrate organs in unraveling pathogenic mechanisms of diseases. In this review and accompanying poster, we highlight the physiological and molecular parallels between fly and human organs that validate the use of Drosophila to study the molecular pathogenesis underlying human diseases. We discuss assays that have been developed in flies to study the function of specific genes in the central nervous system, heart, liver and kidney, and provide examples of the use of these assays to address questions related to human diseases. These assays provide us with simple yet powerful tools to study the pathogenic mechanisms associated with human disease-causing genes.
Topics: Animals; Biological Assay; Disease; Drosophila melanogaster; Humans; Organ Specificity
PubMed: 26935102
DOI: 10.1242/dmm.023762 -
Philosophical Transactions of the Royal... Jan 2009An organism's fitness is critically reliant on its immune system to provide protection against parasites and pathogens. The structure of even simple immune systems is...
An organism's fitness is critically reliant on its immune system to provide protection against parasites and pathogens. The structure of even simple immune systems is surprisingly complex and clearly will have been moulded by the organism's ecology. The aim of this review and the theme issue is to examine the role of different ecological factors on the evolution of immunity. Here, we will provide a general framework of the field by contextualizing the main ecological factors, including interactions with parasites, other types of biotic as well as abiotic interactions, intraspecific selective constraints (life-history trade-offs, sexual selection) and population genetic processes. We then elaborate the resulting immunological consequences such as the diversity of defence mechanisms (e.g. avoidance behaviour, resistance, tolerance), redundancy and protection against immunopathology, life-history integration of the immune response and shared immunity within a community (e.g. social immunity and microbiota-mediated protection). Our review summarizes the concepts of current importance and directs the reader to promising future research avenues that will deepen our understanding of the defence against parasites and pathogens.
Topics: Animals; Biological Evolution; Ecosystem; Genetics, Population; Host-Pathogen Interactions; Humans; Immunity
PubMed: 18926970
DOI: 10.1098/rstb.2008.0249 -
Current Medicinal Chemistry 2019Ciliopathies are a class of inherited pleiotropic genetic disorders in which alterations in cilia assembly, maintenance, and/or function exhibit penetrance in the... (Review)
Review
BACKGROUND
Ciliopathies are a class of inherited pleiotropic genetic disorders in which alterations in cilia assembly, maintenance, and/or function exhibit penetrance in the multiple organ systems. Olfactory dysfunction is one such clinical manifestation that has been shown in both patients and model organisms. Existing therapies for ciliopathies are limited to the treatment or management of symptoms. The last decade has seen an increase in potential curative therapeutic options including small molecules and biologics. Recent work in multiciliated olfactory sensory neurons has demonstrated the capacity of targeted gene therapy to restore ciliation in terminally differentiated cells and rescue olfactory function. This review will discuss the current understanding of the penetrance of ciliopathies in the olfactory system. Importantly, it will highlight both pharmacological and biological approaches, and their potential therapeutic value in the olfactory system and other ciliated tissues.
METHODS
We undertook a structured and comprehensive search of peer-reviewed research literature encompassing in vitro, in vivo, model organism, and clinical studies. From these publications, we describe the olfactory system, and discuss the penetrance of ciliopathies and impact of cilia loss on olfactory function. In addition, we outlined the developing therapies for ciliopathies across different organ and cell culture systems, and discussed their potential therapeutic application to the mammalian olfactory system.
RESULTS
One-hundred sixty-one manuscripts were included in the review, centering on the understanding of olfactory penetrance of ciliopathies, and discussing the potential therapeutic options for ciliopathies in the context of the mammalian olfactory system. Forty-four manuscripts were used to generate a table listing the known congenital causes of olfactory dysfunction, with the first ten listed are linked to ciliopathies. Twenty-three manuscripts were used to outline the potential of small molecules for the olfactory system. Emphasis was placed on HDAC6 inhibitors and lithium, both of which were shown to stabilize microtubule structures, contributing to ciliogenesis and cilia lengthening. Seventy-five manuscripts were used to describe gene therapy and gene therapeutic strategies. Included were the implementation of adenoviral, adeno-associated virus (AAV), and lentiviral vectors to treat ciliopathies across different organ systems and application toward the olfactory system. Thus far, adenoviral and AAVmeditated ciliary restoration demonstrated successful proof-of-principle preclinical studies. In addition, gene editing, ex vivo gene therapy, and transplantation could serve as alternative therapeutic and long-term approaches. But for all approaches, additional assessment of vector immunogenicity, specificity, and efficacy need further investigation. Currently, ciliopathy treatments are limited to symptomatic management with no curative options. However, the accessibility and amenability of the olfactory system to treatment would facilitate development and advancement of a viable therapy.
CONCLUSION
The findings of this review highlight the contribution of ciliopathies to a growing list of congenial olfactory dysfunctions. Promising results from other organ systems imply the feasibility of biologics, with results from gene therapies proving to be a viable therapeutic option for ciliopathies and olfactory dysfunction.
Topics: Animals; Cilia; Ciliopathies; Genetic Therapy; Humans; Olfaction Disorders; Small Molecule Libraries
PubMed: 29303074
DOI: 10.2174/0929867325666180105102447