Metabolomics - the stethoscope for the 21st century

Metabolomics offers systematic identification and quantification of all metabolic products from the human body. This field could provide clinicians with new sets of diagnostic biomarkers for disease states in addition to quantifying treatment response to medications at an individualised level. This literature review aims to highlight the technology underpinning metabolic profiling, identify potential applications of metabolomics in clinical practice and discuss the translational challenges that the field faces. We searched PubMed, Medline and Embase for primary and secondary research articles regarding clinical applications of metabolomics. Metabolic profiling can be performed using mass spectrometry and NMR based techniques using a variety of biological samples. This is carried out in vivo or in vitro following careful sample collection, preparation and analysis. The potential clinical applications constitute disruptive innovations in their respective specialities, particularly oncology and metabolic medicine. Outstanding issues currently preventing widespread clinical use centre around scalability of data interpretation, standardisation of sample handling practice and e-infrastructure. Routine utilisation of metabolomics at a patient and population level will constitute an integral part of future healthcare provision.

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Thrombotect: An Optimized Sample Collection System For The Inhibition Of In Vitro Platelet Release

10.1055/s-0038-1652356 ◽

1981 ◽

Author(s):

E F Workman ◽

D M Clark

Keyword(s):

In Vitro Release ◽

Blood Collection ◽

Sample Collection ◽

Collection System ◽

Platelet Factor ◽

Thrombotic Disease ◽

Disease States ◽

Platelet Release

Platelet activation occurs in a variety of thrombotic disease states and may be monitored via measurement of Platelet Factor 4 (PF4) levels in plasma. In order for PF4 levels to reflect in vivo activation, care must be taken to eliminate in vitro α -granule release during the collection and preparation of blood specimens. Thrombotect is an evacuated blood collection tube containing an anticoagulant (EDTA) and two platelet inhibitors (2-chloroadenosine and procaine-HCl). This system is effective in preventing in vitro release under a variety of centrifugation conditions. Subsequent to a 30 minute icing step, whole blood samples may be centrifuged at room temperature and one of three centrifugation speeds - 2500 × g for 20 minutes,1500 × g for 30 minutes, and 1000 × g for 40 minutes. Plasma specimens from normal individuals were assayed after being prepared under the above conditions. PF4 levels were as follows: 2500 × g, *2.79 ± 1.00 (73); 1500 × g, 3.84 ±1.78 (20); 1000 × g, 3.35 ± 1.65 (20). Variations in the temperature of centrifugation had little effect on the ability of Thrombotect to inhibit PF4 release, whereas other commonly used blood collection cocktails became progressively less effective with increasing temperature.*(Mean PF4 in ng/ml ± 1 S.D., “n” values in parenthesis). Results similar to those obtained for EDTA/Theophylline were obtained when EDTA was used in conjunction with adenosine and/or aspirin. The Thrombotect system has been employed in an examination of PF4 levels in a variety of thrombotic disease states. It also provides an excellent collection system for use with other “platelet-release” assays.

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Lentiviral Vectors for Delivery of Gene-Editing Systems Based on CRISPR/Cas: Current State and Perspectives

Viruses ◽

10.3390/v13071288 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1288

Author(s):

Wendy Dong ◽

Boris Kantor

Keyword(s):

Large Scale ◽

Lentiviral Vector ◽

Clinical Applications ◽

Scale Production ◽

Base Editing ◽

Epigenome Editing ◽

Vector Systems ◽

Dividing Cells

CRISPR/Cas technology has revolutionized the fields of the genome- and epigenome-editing by supplying unparalleled control over genomic sequences and expression. Lentiviral vector (LV) systems are one of the main delivery vehicles for the CRISPR/Cas systems due to (i) its ability to carry bulky and complex transgenes and (ii) sustain robust and long-term expression in a broad range of dividing and non-dividing cells in vitro and in vivo. It is thus reasonable that substantial effort has been allocated towards the development of the improved and optimized LV systems for effective and accurate gene-to-cell transfer of CRISPR/Cas tools. The main effort on that end has been put towards the improvement and optimization of the vector’s expression, development of integrase-deficient lentiviral vector (IDLV), aiming to minimize the risk of oncogenicity, toxicity, and pathogenicity, and enhancing manufacturing protocols for clinical applications required large-scale production. In this review, we will devote attention to (i) the basic biology of lentiviruses, and (ii) recent advances in the development of safer and more efficient CRISPR/Cas vector systems towards their use in preclinical and clinical applications. In addition, we will discuss in detail the recent progress in the repurposing of CRISPR/Cas systems related to base-editing and prime-editing applications.

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Characterization of phase I and phase II metabolites of hop (Humulus lupulus L.) bitter acids: In vitro and in vivo metabolic profiling by UHPLC-Q-Orbitrap

Journal of Pharmaceutical and Biomedical Analysis ◽

10.1016/j.jpba.2021.114107 ◽

2021 ◽

pp. 114107

Author(s):

Emanuela Salviati ◽

Eduardo Sommella ◽

Albino Carrizzo ◽

Veronica Di Sarno ◽

Alessia Bertamino ◽

...

Keyword(s):

Phase I ◽

Phase Ii ◽

Metabolic Profiling ◽

Humulus Lupulus ◽

Humulus Lupulus L ◽

Bitter Acids ◽

Phase Ii Metabolites

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Synthesis and Characterization of Polyvinylpyrrolidone-Modified ZnO Quantum Dots and Their In Vitro Photodynamic Tumor Suppressive Action

International Journal of Molecular Sciences ◽

10.3390/ijms22158106 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8106

Author(s):

Tianming Song ◽

Yawei Qu ◽

Zhe Ren ◽

Shuang Yu ◽

Mingjian Sun ◽

...

Keyword(s):

Quantum Dots ◽

Photodynamic Therapy ◽

Inhibitory Effect ◽

Therapeutic Effects ◽

In Vivo Experiments ◽

Potential Applications ◽

Zno Quantum Dots ◽

Zno Qds

Despite the numerous available treatments for cancer, many patients succumb to side effects and reoccurrence. Zinc oxide (ZnO) quantum dots (QDs) are inexpensive inorganic nanomaterials with potential applications in photodynamic therapy. To verify the photoluminescence of ZnO QDs and determine their inhibitory effect on tumors, we synthesized and characterized ZnO QDs modified with polyvinylpyrrolidone. The photoluminescent properties and reactive oxygen species levels of these ZnO/PVP QDs were also measured. Finally, in vitro and in vivo experiments were performed to test their photodynamic therapeutic effects in SW480 cancer cells and female nude mice. Our results indicate that the ZnO QDs had good photoluminescence and exerted an obvious inhibitory effect on SW480 tumor cells. These findings illustrate the potential applications of ZnO QDs in the fields of photoluminescence and photodynamic therapy.

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Production of Human Pluripotent Stem Cell-Derived Hepatic Cell Lineages and Liver Organoids: Current Status and Potential Applications

Bioengineering ◽

10.3390/bioengineering7020036 ◽

2020 ◽

Vol 7 (2) ◽

pp. 36 ◽

Cited By ~ 5

Author(s):

João P. Cotovio ◽

Tiago G. Fernandes

Keyword(s):

Cell Types ◽

In Vitro Models ◽

Hepatic Cell ◽

Current Status ◽

Organ Shortage ◽

Cell Lineages ◽

Potential Applications ◽

Liver Organoids

Liver disease is one of the leading causes of death worldwide, leading to the death of approximately 2 million people per year. Current therapies include orthotopic liver transplantation, however, donor organ shortage remains a great challenge. In addition, the development of novel therapeutics has been limited due to the lack of in vitro models that mimic in vivo liver physiology. Accordingly, hepatic cell lineages derived from human pluripotent stem cells (hPSCs) represent a promising cell source for liver cell therapy, disease modelling, and drug discovery. Moreover, the development of new culture systems bringing together the multiple liver-specific hepatic cell types triggered the development of hPSC-derived liver organoids. Therefore, these human liver-based platforms hold great potential for clinical applications. In this review, the production of the different hepatic cell lineages from hPSCs, including hepatocytes, as well as the emerging strategies to generate hPSC-derived liver organoids will be assessed, while current biomedical applications will be highlighted.

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Cellular and immunological basis of the host-parasite relationship during infection withNeospora caninum

Parasitology ◽

10.1017/s0031182006000485 ◽

2006 ◽

Vol 133 (3) ◽

pp. 261-278 ◽

Cited By ~ 76

Author(s):

A. HEMPHILL ◽

N. VONLAUFEN ◽

A. NAGULESWARAN

Keyword(s):

Host Cell ◽

Cell Biology ◽

Neospora Caninum ◽

Host Cells ◽

Term Survival ◽

Prevention Of Infection ◽

Parasite Relationship ◽

Potential Applications

Neospora caninumis an apicomplexan parasite that is closely related toToxoplasma gondii, the causative agent of toxoplasmosis in humans and domestic animals. However, in contrast toT. gondii, N. caninumrepresents a major cause of abortion in cattle, pointing towards distinct differences in the biology of these two species. There are 3 distinct key features that represent potential targets for prevention of infection or intervention against disease caused byN. caninum. Firstly, tachyzoites are capable of infecting a large variety of host cellsin vitroandin vivo. Secondly, the parasite exploits its ability to respond to alterations in living conditions by converting into another stage (tachyzoite-to-bradyzoite orvice versa). Thirdly, by analogy withT. gondii, this parasite has evolved mechanisms that modulate its host cells according to its own requirements, and these must, especially in the case of the bradyzoite stage, involve mechanisms that ensure long-term survival of not only the parasite but also of the host cell. In order to elucidate the molecular and cellular bases of these important features ofN. caninum, cell culture-based approaches and laboratory animal models are being exploited. In this review, we will summarize the current achievements related to host cell and parasite cell biology, and will discuss potential applications for prevention of infection and/or disease by reviewing corresponding work performed in murine laboratory infection models and in cattle.

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