scholarly journals Synthetic biology devices for in vitro and in vivo diagnostics

2015 ◽  
Vol 112 (47) ◽  
pp. 14429-14435 ◽  
Author(s):  
Shimyn Slomovic ◽  
Keith Pardee ◽  
James J. Collins
Keyword(s):  
Synthetic Biology ◽  
Diagnostic Tools ◽  
Emerging Pathogens ◽  
Laboratory Equipment ◽  
Gene Circuits ◽  
Pathological Conditions ◽  
In Vivo Diagnostics ◽  
Production Cycles

There is a growing need to enhance our capabilities in medical and environmental diagnostics. Synthetic biologists have begun to focus their biomolecular engineering approaches toward this goal, offering promising results that could lead to the development of new classes of inexpensive, rapidly deployable diagnostics. Many conventional diagnostics rely on antibody-based platforms that, although exquisitely sensitive, are slow and costly to generate and cannot readily confront rapidly emerging pathogens or be applied to orphan diseases. Synthetic biology, with its rational and short design-to-production cycles, has the potential to overcome many of these limitations. Synthetic biology devices, such as engineered gene circuits, bring new capabilities to molecular diagnostics, expanding the molecular detection palette, creating dynamic sensors, and untethering reactions from laboratory equipment. The field is also beginning to move toward in vivo diagnostics, which could provide near real-time surveillance of multiple pathological conditions. Here, we describe current efforts in synthetic biology, focusing on the translation of promising technologies into pragmatic diagnostic tools and platforms.

scholarly journals Induction of Host Chemotactic Response by Encephalitozoon spp.

2006 ◽  
Vol 75 (4) ◽  
pp. 1619-1625 ◽  
Author(s):  
Jeffrey Fischer ◽  
Jeffrey West ◽  
Nnenaya Agochukwu ◽  
Colby Suire ◽  
Hollie Hale-Donze
Keyword(s):  
Inflammatory Responses ◽  
Kinetic Studies ◽  
Protein Profiling ◽  
Diagnostic Tools ◽  
Emerging Pathogens ◽  
Chemokine Production ◽  
Human Macrophages ◽  
Monocyte Migration

ABSTRACT Microsporidians are a group of emerging pathogens typically associated with chronic diarrhea in immunocompromised individuals. The number of reports of infections with these organisms and the disseminated pathology is growing as diagnostic tools become more readily available. However, little is known about the innate immune response induced by and generated against these parasites. Using a coculture chemotaxis system, primary human macrophages were infected with Encephalitozoon cuniculi or Encephalitozoon intestinalis, and the recruitment of naïve monocytes was monitored. Encephalitozoon spp. induced an average threefold increase in migration of naïve cells 48 h postinfection, which corresponded to optimal infection of monocyte-derived-macrophages. A limited microarray analysis of infected macrophages revealed several chemokines involved in the inflammatory responses whose expression was upregulated, including CCL1, CCL2, CCL3, CCL4, CCL7, CCL15, CCL20, CXCL1, CXCL2, CXCL3, CXCL5, and CXCL8. The levels of 6 of 11 chemokines also present in the microarray were confirmed to be elevated by protein profiling. Kinetic studies confirmed that secreted CCL2, CCL3, and CCL4 were expressed as early as 6 h postinfection, with peak expression at 12 to 24 h and expression remaining until 48 h postinfection. Neutralization of these chemokines, specifically CCL4, significantly reduced the number of migrating cells in vitro, indicating their role in the induction of monocyte migration. This mechanism of recruitment not only supports the evidence that in vivo cellular infiltration occurs but also provides new hosts for the parasites, which escape macrophages by rupturing the host cell. To our knowledge, this is the first documentation that chemokine production is induced by microsporidian infections in human macrophages.

scholarly journals Pharmacological Effects and Potential Clinical Usefulness of Polyphenols in Benign Prostatic Hyperplasia

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 450
Author(s):  
Kensuke Mitsunari ◽  
Yasuyoshi Miyata ◽  
Tomohiro Matsuo ◽  
Yuta Mukae ◽  
Asato Otsubo ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Molecular Mechanisms ◽  
Prostatic Hyperplasia ◽  
Pathological Conditions ◽  
Urinary Tract Symptoms ◽  
Anti Inflammatory ◽  
Lower Urinary

Benign prostatic hyperplasia (BPH) is arguably the most common benign disease among men. This disease is often associated with lower urinary tract symptoms (LUTS) in men and significantly decreases the quality of life. Polyphenol consumption reportedly plays an important role in the prevention of many diseases, including BPH. In recent years, in addition to disease prevention, many studies have reported the efficacy and safety of polyphenol treatment against various pathological conditions in vivo and in vitro. Furthermore, numerous studies have also revealed the molecular mechanisms of the antioxidant and anti-inflammatory effects of polyphenols. We believe that an improved understanding of the detailed pharmacological roles of polyphenol-induced activities at a molecular level is important for the prevention and treatment of BPH. Polyphenols are composed of many members, and their biological roles differ. In this review, we first provide information regarding the pathological roles of oxidative stress and inflammation in BPH. Next, the antioxidant and anti-inflammatory effects of polyphenols, including those of flavonoids and non-flavonoids, are discussed. Finally, we talk about the results and limitations of previous clinical trials that have used polyphenols in BPH, with particular focus on their molecular mechanisms of action.

scholarly journals Application of Volatilome Analysis to the Diagnosis of Mycobacteria Infection in Livestock

2021 ◽  
Vol 8 ◽  
Author(s):  
Pablo Rodríguez-Hernández ◽  
Vicente Rodríguez-Estévez ◽  
Lourdes Arce ◽  
Jaime Gómez-Laguna
Keyword(s):  
Analytical Techniques ◽  
Diagnostic Techniques ◽  
Diagnostic Tools ◽  
Future Research ◽  
Control Programs ◽  
Targeted Analysis ◽  
Low Sensitivity ◽  
And Control

Volatile organic compounds (VOCs) are small molecular mass metabolites which compose the volatilome, whose analysis has been widely employed in different areas. This innovative approach has emerged in research as a diagnostic alternative to different diseases in human and veterinary medicine, which still present constraints regarding analytical and diagnostic sensitivity. Such is the case of the infection by mycobacteria responsible for tuberculosis and paratuberculosis in livestock. Although eradication and control programs have been partly managed with success in many countries worldwide, the often low sensitivity of the current diagnostic techniques against Mycobacterium bovis (as well as other mycobacteria from Mycobacterium tuberculosis complex) and Mycobacterium avium subsp. paratuberculosis together with other hurdles such as low mycobacteria loads in samples, a tedious process of microbiological culture, inhibition by many variables, or intermittent shedding of the mycobacteria highlight the importance of evaluating new techniques that open different options and complement the diagnostic paradigm. In this sense, volatilome analysis stands as a potential option because it fulfills part of the mycobacterial diagnosis requirements. The aim of the present review is to compile the information related to the diagnosis of tuberculosis and paratuberculosis in livestock through the analysis of VOCs by using different biological matrices. The analytical techniques used for the evaluation of VOCs are discussed focusing on the advantages and drawbacks offered compared with the routine diagnostic tools. In addition, the differences described in the literature among in vivo and in vitro assays, natural and experimental infections, and the use of specific VOCs (targeted analysis) and complete VOC pattern (non-targeted analysis) are highlighted. This review emphasizes how this methodology could be useful in the problematic diagnosis of tuberculosis and paratuberculosis in livestock and poses challenges to be addressed in future research.

scholarly journals Gene-Based Antibody Strategies for Prion Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Alessio Cardinale ◽  
Silvia Biocca
Keyword(s):  
Therapeutic Potential ◽  
Prion Diseases ◽  
Recombinant Antibody ◽  
Cellular Protein ◽  
Transmissible Spongiform Encephalopathies ◽  
Diagnostic Tools ◽  
Spongiform Encephalopathies ◽  
Interaction Sites

Prion diseases or transmissible spongiform encephalopathies (TSE) are a group of neurodegenerative and infectious disorders characterized by the conversion of a normal cellular protein PrPCinto a pathological abnormally folded form, termed PrPSc. There are neither available therapies nor diagnostic tools for an early identification of individuals affected by these diseases. New gene-based antibody strategies are emerging as valuable therapeutic tools. Among these, intrabodies are chimeric molecules composed by recombinant antibody fragments fused to intracellular trafficking sequences, aimed at inhibiting,in vivo, the function of specific therapeutic targets. The advantage of intrabodies is that they can be selected against a precise epitope of target proteins, including protein-protein interaction sites and cytotoxic conformers (i.e., oligomeric and fibrillar assemblies). Herein, we address and discussin vitroandin vivoapplications of intrabodies in prion diseases, focussing on their therapeutic potential.

scholarly journals Nutraceuticals in Thyroidology: A Review of in Vitro, and in Vivo Animal Studies

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1337
Author(s):  
Salvatore Benvenga ◽  
Silvia Martina Ferrari ◽  
Giusy Elia ◽  
Francesca Ragusa ◽  
Armando Patrizio ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Animal Studies ◽  
Experimental Studies ◽  
Omega 3 ◽  
Complementary Medicines ◽  
Pathological Conditions ◽  
Potential Risks ◽  
Dietary Components

Nutraceuticals are defined as a food, or parts of a food, that provide medical or health benefits, including the prevention of different pathological conditions, and thyroid diseases, or the treatment of them. Nutraceuticals have a place in complementary medicines, being positioned in an area among food, food supplements, and pharmaceuticals. The market of certain nutraceuticals such as thyroid supplements has been growing in the last years. In addition, iodine is a fundamental micronutrient for thyroid function, but also other dietary components can have a key role in clinical thyroidology. Here, we have summarized the in vitro, and in vivo animal studies present in literature, focusing on the commonest nutraceuticals generally encountered in the clinical practice (such as carnitine, flavonoids, melatonin, omega-3, resveratrol, selenium, vitamins, zinc, and inositol), highlighting conflicting results. These experimental studies are expected to improve clinicians’ knowledge about the main supplements being used, in order to clarify the potential risks or side effects and support patients in their use.

scholarly journals In vivo and in vitro genotoxicity studies of aqueous extract of Xanthium spinosum

2012 ◽  
Vol 48 (3) ◽  
pp. 461-467 ◽  
Author(s):  
Camila Martins Güez ◽  
Emily Pansera Waczuk ◽  
Karina Braccini Pereira ◽  
Marcus Vinícius Morini Querol ◽  
João Batista Teixeira da Rocha ◽  
...  
Keyword(s):  
Aqueous Extract ◽  
Micronucleus Test ◽  
Cell Damage ◽  
Damage Index ◽  
Real Effects ◽  
Pathological Conditions ◽  
Cells With Micronuclei ◽  
In Vitro Genotoxicity

The use of plants as a source of palliative or cure for pathological conditions is quite common worldwide. Xanthium spinosum (Asteraceae), popularly known in Brazil as 'espinho de carneiro', is an annual weed from South America, which has been used by empiric medicine to treat neoplasias. Owing to the extensive use of the above-mentioned plant and to the lack of reports about the real effects of its infusion, current study evaluated the genotoxic potential of its aqueous extract at concentrations 0.02 g L-1, 0.1 g L-1 and 0.2 g L-1 by fish micronucleus test and by comet human leukocytes assay. The micronucleus test featured at least 50 cells with micronuclei to every 2,000 cells scored, as a mutagenic parameter. The comet assay was used as a parameter for assessing the level of cell damage and the damage index. Since no significant changes in strain cells exposed to the aqueous extract in the comet and micronucleus assays were reported, it seems that no genotoxicity evidence is extant at the concentrations and in the assays performed.

scholarly journals Strains, Mechanism, and Perspective:Salmonella-Based Cancer Therapy

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Cheng-Zhi Wang ◽  
Robert A. Kazmierczak ◽  
Abraham Eisenstark
Keyword(s):  
Synthetic Biology ◽  
Tumor Targeting ◽  
Tumor Therapy ◽  
The Other ◽  
Cancer Therapies ◽  
Chemotherapeutic Drugs ◽  
Serovar Typhimurium ◽  
Candidate Strain

Recently, investigation of bacterial-based tumor therapy has regained focus due to progress in molecular, cellular, and microbial biology. Many bacteria such asSalmonella,Listeria,Escherichia, andClostridiumhave proved to have tumor targeting and in some cases even tumor-destroying phenotypes. Furthermore, bacterial clinical treatments for cancer have been improved by combination with other therapeutic methods such as chemotherapeutic drugs and radioactive agents. Synthetic biology techniques have also driven the development of new bacterial-based cancer therapies. However, basic questions about the mechanisms of bacterial-mediated tumor targeting and destruction are still being elucidated. In this review, we focus on three tumor-therapeuticSalmonellamodels, the most intensively studied bacterial genus in this field. One of theseSalmonellamodels is ourSalmonella entericaserovar Typhimurium LT2 derived strain CRC2631, engineered to minimize toxicity but maximize tumor-targeting and destruction effects. The other two are VNP20009 and A1-R. We compare the means by which these therapeutic candidate strain models were selected for study, their tumor targeting and tumor destruction phenotypesin vitroandin vivo, and what is currently known about the mechanisms by which they target and destroy tumors.

scholarly journals Regulating synthetic gene networks in 3D materials

2012 ◽  
Vol 109 (38) ◽  
pp. 15217-15222 ◽  
Author(s):  
Tara L. Deans ◽  
Anirudha Singh ◽  
Matthew Gibson ◽  
Jennifer H. Elisseeff
Keyword(s):  
Synthetic Biology ◽  
Gene Networks ◽  
Materials Science ◽  
Genetic Circuits ◽  
Therapeutic Applications ◽  
Regulatory Processes ◽  
Cellular Events ◽  
The Matrix

Combining synthetic biology and materials science will enable more advanced studies of cellular regulatory processes, in addition to facilitating therapeutic applications of engineered gene networks. One approach is to couple genetic inducers into biomaterials, thereby generating 3D microenvironments that are capable of controlling intrinsic and extrinsic cellular events. Here, we have engineered biomaterials to present the genetic inducer, IPTG, with different modes of activating genetic circuits in vitro and in vivo. Gene circuits were activated in materials with IPTG embedded within the scaffold walls or chemically linked to the matrix. In addition, systemic applications of IPTG were used to induce genetic circuits in cells encapsulated into materials and implanted in vivo. The flexibility of modifying biomaterials with genetic inducers allows for patterned placement of these inducers that can be used to generate distinct patterns of gene expression. Together, these genetically interactive materials can be used to characterize genetic circuits in environments that more closely mimic cells’ natural 3D settings, to better explore complex cell–matrix and cell–cell interactions, and to facilitate therapeutic applications of synthetic biology.

scholarly journals Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering

2016 ◽  
Vol 13 (117) ◽  
pp. 20151046 ◽  
Author(s):  
Fei He ◽  
Ettore Murabito ◽  
Hans V. Westerhoff
Keyword(s):  
Systems Biology ◽  
Synthetic Biology ◽  
Regulatory Networks ◽  
Computational Systems Biology ◽  
Control Engineering ◽  
Trade Offs ◽  
Metabolic Systems ◽  
Analytical Approaches

Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo , not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways.

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