scholarly journals Real-time nanodiamond thermometry probing in vivo thermogenic responses

2020 ◽  
Vol 6 (37) ◽  
pp. eaba9636 ◽  
Author(s):  
Masazumi Fujiwara ◽  
Simo Sun ◽  
Alexander Dohms ◽  
Yushi Nishimura ◽  
Ken Suto ◽  
...  

Real-time temperature monitoring inside living organisms provides a direct measure of their biological activities. However, it is challenging to reduce the size of biocompatible thermometers down to submicrometers, despite their potential applications for the thermal imaging of subtissue structures with single-cell resolution. Here, using quantum nanothermometers based on optically accessible electron spins in nanodiamonds, we demonstrate in vivo real-time temperature monitoring inside Caenorhabditis elegans worms. We developed a microscope system that integrates a quick-docking sample chamber, particle tracking, and an error correction filter for temperature monitoring of mobile nanodiamonds inside live adult worms with a precision of ±0.22°C. With this system, we determined temperature increases based on the worms’ thermogenic responses during the chemical stimuli of mitochondrial uncouplers. Our technique demonstrates the submicrometer localization of temperature information in living animals and direct identification of their pharmacological thermogenesis, which may allow for quantification of their biological activities based on temperature.

2018 ◽  
Author(s):  
Mahendran Subramanian ◽  
Arkadiusz Miaskowski ◽  
Ajit K. Mahapatro ◽  
Ondrej Hovorka ◽  
Jon Dobson

AbstractHeat dissipation during magnetization reversal processes in magnetic nanoparticles (MNP), upon exposure to alternating magnetic fields (AMF), has been extensively studied in relation to applications in magnetic fluid hyperthermia (MFH). This current paper demonstrates the design, fabrication, and evaluation of an efficient instrument, operating on this principle, for use as (i) a non-contact, in vitro, real-time temperature monitor; (ii) a drug release analysis system (DRAS); (iii) a high flux density module for AMF-mediated MNP studies; and (iv) an in vivo coil setup for real-time, whole body thermal imaging. The proposed DRAS is demonstrated by an AMF-mediated drug release proof-of-principle experiment. Also, the technique described facilitates non-contact temperature measurements of specific absorption rate (SAR) as accurately as temperature measurements using a probe in contact with the sample. Numerical calculations estimating the absolute and root mean squared flux densities, and other MNP – AMF studies suggest that the proposed stacked planar coil module could be employed for calorimetry. Even though the proposed in vivo coil setup could be used for real-time, whole body thermal imaging (within the limitations due to issues of penetration depth), further design effort is required in order to enhance the energy transfer efficiency.


2020 ◽  
Author(s):  
Norimichi Koitabashi ◽  
Riki Ogasawara ◽  
Ryuto Yasui ◽  
Yuki Sugiura ◽  
Hinako Matsuda ◽  
...  

ABSTRACTAnalysis of the dynamics of adenosine triphosphate (ATP) is vital to quantitatively define the actual roles of ATP in biological activities. Here, we applied a genetically encoded Förster resonance energy transfer biosensor “GO-ATeam” and created a transgenic mouse model that allows systemic ATP levels to be quantitatively, sensitively, noninvasively, and spatiotemporally measured under physiological and pathological conditions. We used this model to readily conduct intravital imaging of ATP dynamics under three different conditions: during exercise, in all organs and cells; during myocardial infarction progression; and in response to the application of cardiotoxic drugs. These findings provide compelling evidence that the GO-ATeam mouse model is a powerful tool to investigate the multifarious functions of cellular ATP in vivo with unprecedented spatiotemporal resolution in real-time. This will inform predictions of molecular and morphological responses to perturbations of ATP levels, as well as the elucidation of physiological mechanisms that control ATP homeostasis.One Sentence SummaryIntravital real-time imaging of ATP dynamics in multiple organs using GO-ATeam mice, can be used to quantitatively, sensitively, noninvasively, and spatiotemporally measure systemic ATP levels and provide a platform for preclinical pharmacological studies.


2020 ◽  
Vol 26 (7) ◽  
pp. 772-779 ◽  
Author(s):  
Md. Ataur Rahman ◽  
Md Rezanur Rahman ◽  
Toyfiquz Zaman ◽  
Md. Sahab Uddin ◽  
Rokibul Islam ◽  
...  

Background: Naturally-occurring products derived from living organisms have been shown to modulate various pharmacological and biological activities. Natural products protect against various diseases, which could be used for therapeutic assistance. Autophagy, a lysosome-mediated self-digestion pathway, has been implicated in a range of pathophysiological conditions and has recently gained attention for its role in several neurodegenerative diseases. Methods: In this current review, we emphasized the recent progress made in our understanding of the molecular mechanism of autophagy in different cellular and mouse models using naturally-occurring autophagy modulators for the management of several neurodegenerative diseases. Results: Accumulating evidence has revealed that a wide variety of natural compounds such as alkaloids, polyphenols, terpenoids, xanthonoids, flavonoids, lignans, disaccharides, glycolipoproteins, and saponins are involved in the modulation of the autophagy signaling pathway. These natural products have been used to treat various neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Amyotrophic lateral sclerosis, spinocerebellar ataxia, neuroblastoma, and glioblastoma. Although a number of synthetic autophagy regulators have been recognized as encouraging neurodegenerative therapeutic candidates, natural autophagy- regulating compounds have been of further interest as potential disease therapeutics, as they cause insignificant side effects. Conclusion: Existing in vitro and in vivo data are promising and highlight that naturally-occurring autophagyregulating compounds play an important role in the prevention and treatment of neurodegenerative disorders.


2019 ◽  
Vol 4 (12) ◽  
Author(s):  
Abraham Madariaga-Mazón ◽  
Ricardo Bruno Hernández-Alvarado ◽  
Karla Olivia Noriega-Colima ◽  
Adriana Osnaya-Hernández ◽  
Karina Martinez-Mayorga

Abstract Secondary metabolites, commonly referred to as natural products, are produced by living organisms and usually have pharmacological or biological activities. Secondary metabolites are the primary source for the discovery of new drugs. Furthermore, secondary metabolites are also used as food preservatives, biopesticides or as research tools. Although secondary metabolites are mainly used by their beneficial biological activity, the toxicity of some of them may limit their use. The toxicity assessment of any compound that is prone to be used in direct contact with human beings is of vital importance. There is a vast spectrum of experimental methods for toxicity evaluation, including in vitro and in vivo methodologies. In this work, we present an overview of the different sources, bioactivities, toxicities and chemical classification of secondary metabolites, followed by a sketch of the role of toxicity assessment in drug discovery and agrochemistry.


2021 ◽  
Vol 13 (1) ◽  
pp. 110-126
Author(s):  
Ruchi Sankhwar ◽  
Shilpi Yadav ◽  
Abhishek Kumar ◽  
Ravi Kr. Gupta

Gram-positive bacteria cause various diseases from the superficial skin to deep tissue infections. The capability of causing numerous diseases is due to the production of virulence factors which are tightly regulated by the virulence genes. Various Gram-positive pathogenic bacteria e.g. Staphylococcus, Mycobacterium, and Listeria are capable of causing lethal infections in humans and animals. Conventional antibiotics, targeted antibiotics, and combinatorial drugs are used as therapeutic agents against Gram-positive pathogens. Due to intricate virulence pathway bacteria readily adopt resistance to available drugs. Therefore, there is need to develop some alternative approaches to combat these infections. Various natural extracts are effective against pathogenic bacteria with or without the available drugs. Curcumin is a natural extract of Curcuma longas rhizome, known as turmeric. Curcumin shows various biological activities such as antimicrobial, antioxidant and anti-inflammatory. It also shows strong antibacterial activity against Gram-positive and few Gram-negative bacteria. Besides all these beneficial applications, major drawbacks of curcumin are poor aqueous solubility and less bioavailability. However, drug delivery approaches including nanoformulation are developed to increase its stability in vitro and in vivo settings. The present review article focused on the translation of potential applications of curcumin in various diseases specifically caused by Gram-positive pathogens. Various methods used for the formulations of curcumin nanoparticles, combinatorial strategies with curcumin nanoparticles and their application in the prevention of infections have been discussed. The present article also discusses the future aspects of curcumin-nanoparticles and its use as an alternative therapeutic approach against pathogens.


Author(s):  
Paweł Bakun ◽  
Beata Czarczynska-Goslinska ◽  
Tomasz Goslinski ◽  
Sebastian Lijewski

AbstractAzulene is an aromatic hydrocarbon that possesses a unique chemical structure and interesting biological properties. Azulene derivatives, including guaiazulene or chamazulene, occur in nature as components of many plants and mushrooms, such as Matricaria chamomilla, Artemisia absinthium, Achillea millefolium, and Lactarius indigo. Due to physicochemical properties, azulene and its derivatives have found many potential applications in technology, especially in optoelectronic devices. In medicine, the ingredients of these plants have been widely used for hundreds of years in antiallergic, antibacterial, and anti-inflammatory therapies. Herein, the applications of azulene, its derivatives and their conjugates with biologically active compounds are presented. The potential use of these compounds concerns various areas of medicine, including anti-inflammatory with peptic ulcers, antineoplastic with leukemia, antidiabetes, antiretroviral with HIV-1, antimicrobial, including antimicrobial photodynamic therapy, and antifungal.


Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1084
Author(s):  
Zuzanna Sobańska ◽  
Joanna Roszak ◽  
Kornelia Kowalczyk ◽  
Maciej Stępnik

The expanding applications of nanotechnology seem to be a response to many technological, environmental, and medical challenges. The unique properties of nanoparticles allow for developing new technologies and therapies. Among many investigated compounds is manganese and its oxides, which in the form of nanoparticles, could be a promising alternative for gadolinium-based contrast agents used in diagnostic imaging. Manganese, which is essential for living organisms as an enzyme cofactor, under excessive exposure—for example, due to water contamination or as an occupational hazard for welders—can lead to neurological disorders, including manganism—a condition similar to Parkinson’s disease. This review attempts to summarise the available literature data on the potential applications of manganese and manganese oxide nanoparticles and their biological activity. Some of the published studies, both in vitro and in vivo, show negative effects of exposure to manganese, mainly on the nervous system, whereas other data suggest that it is possible to develop functionalised nanoparticles with negligible toxicity and novel promising properties.


Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 673
Author(s):  
Yan Liu ◽  
Yali Shen ◽  
Yang Song ◽  
Lei Xu ◽  
J. Jefferson P. P. Perry ◽  
...  

Isopeptidase activity of proteases plays critical roles in physiological and pathological processes in living organisms, such as protein stability in cancers and protein activity in infectious diseases. However, the kinetics of protease isopeptidase activity has not been explored before due to a lack of methodology. Here, we report the development of novel qFRET-based protease assay for characterizing the isopeptidase kinetics of SENP1. The reversible process of SUMOylation in vivo requires an enzymatic cascade that includes E1, E2, and E3 enzymes and Sentrin/SUMO-specific proteases (SENPs), which can act either as endopeptidases that process the pre-SUMO before its conjugation, or as isopeptidases to deconjugate SUMO from its target substrate. We first produced the isopeptidase substrate of CyPet-SUMO1/YPet-RanGAP1c by SUMOylation reaction in the presence of SUMO E1 and E2 enzymes. Then a qFRET analyses of real-time FRET signal reduction of the conjugated substrate of CyPet-SUMO1/YPet-RanGAP1c to free CyPet-SUMO1 and YPet-RanGAP1c by the SENP1 were able to obtain the kinetic parameters, Kcat, KM, and catalytic efficiency (Kcat/KM) of SENP1. This represents a pioneer effort in isopeptidase kinetics determination. Importantly, the general methodology of qFRET-based protease isopeptidase kinetic determination can also be applied to other proteases.


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