“…Additionally, it has been shown that molecular sensors based on donor-acceptor energy transfer-have been also used to detect a number of intracellular species such as nitroxyl (HNO) (Ali et al, 2017 ), hydrogen peroxide (H 2 O 2 ) (Albers et al, 2006 ; Wu et al, 2017 ), H 3 O + (Li et al, 2017 ), ions such as Hg 2+ (Singh et al, 2017 ), Pd 2+ (Li et al, 2018 ), Zn 2+ (Hessels and Merkx, 2015 ), and mRNA (Ou et al, 2017 ). Furthermore, several aspects on the use of FRET biosensors for optical signaling of biological processes have been extensively reviewed (Müller et al, 2013 ; Kaestner et al, 2015 ; Stumpf and Hoffmann, 2016 ; Alam et al, 2017 ; Bohórquez-Hernández et al, 2017 ; Zheng et al, 2017 ; Ujlaky-Nagy et al, 2018 ).…”
Section: Optical Sensing Approaches: the Role Of Oxygen Quenchingmentioning
Hypoxia has been identified as one of the hallmarks of tumor environments and a prognosis factor in many cancers. The development of ideal chemical probes for imaging and sensing of hypoxia remains elusive. Crucial characteristics would include a measurable response to subtle variations of pO2 in living systems and an ability to accumulate only in the areas of interest (e.g., targeting hypoxia tissues) whilst exhibiting kinetic stabilities in vitro and in vivo. A sensitive probe would comprise platforms for applications in imaging and therapy for non-communicable diseases (NCDs) relying on sensitive detection of pO2. Just a handful of probes for the in vivo imaging of hypoxia [mainly using positron emission tomography (PET)] have reached the clinical research stage. Many chemical compounds, whilst presenting promising in vitro results as oxygen-sensing probes, are facing considerable disadvantages regarding their general application in vivo. The mechanisms of action of many hypoxia tracers have not been entirely rationalized, especially in the case of metallo-probes. An insight into the hypoxia selectivity mechanisms can allow an optimization of current imaging probes candidates and this will be explored hereby. The mechanistic understanding of the modes of action of coordination compounds under oxygen concentration gradients in living cells allows an expansion of the scope of compounds toward in vivo applications which, in turn, would help translate these into clinical applications. We summarize hereby some of the recent research efforts made toward the discovery of new oxygen sensing molecules having a metal-ligand core. We discuss their applications in vitro and/or in vivo, with an appreciation of a plethora of molecular imaging techniques (mainly reliant on nuclear medicine techniques) currently applied in the detection and tracing of hypoxia in the preclinical and clinical setups. The design of imaging/sensing probe for early-stage diagnosis would longer term avoid invasive procedures providing platforms for therapy monitoring in a variety of NCDs and, particularly, in cancers.
“…Additionally, it has been shown that molecular sensors based on donor-acceptor energy transfer-have been also used to detect a number of intracellular species such as nitroxyl (HNO) (Ali et al, 2017 ), hydrogen peroxide (H 2 O 2 ) (Albers et al, 2006 ; Wu et al, 2017 ), H 3 O + (Li et al, 2017 ), ions such as Hg 2+ (Singh et al, 2017 ), Pd 2+ (Li et al, 2018 ), Zn 2+ (Hessels and Merkx, 2015 ), and mRNA (Ou et al, 2017 ). Furthermore, several aspects on the use of FRET biosensors for optical signaling of biological processes have been extensively reviewed (Müller et al, 2013 ; Kaestner et al, 2015 ; Stumpf and Hoffmann, 2016 ; Alam et al, 2017 ; Bohórquez-Hernández et al, 2017 ; Zheng et al, 2017 ; Ujlaky-Nagy et al, 2018 ).…”
Section: Optical Sensing Approaches: the Role Of Oxygen Quenchingmentioning
Hypoxia has been identified as one of the hallmarks of tumor environments and a prognosis factor in many cancers. The development of ideal chemical probes for imaging and sensing of hypoxia remains elusive. Crucial characteristics would include a measurable response to subtle variations of pO2 in living systems and an ability to accumulate only in the areas of interest (e.g., targeting hypoxia tissues) whilst exhibiting kinetic stabilities in vitro and in vivo. A sensitive probe would comprise platforms for applications in imaging and therapy for non-communicable diseases (NCDs) relying on sensitive detection of pO2. Just a handful of probes for the in vivo imaging of hypoxia [mainly using positron emission tomography (PET)] have reached the clinical research stage. Many chemical compounds, whilst presenting promising in vitro results as oxygen-sensing probes, are facing considerable disadvantages regarding their general application in vivo. The mechanisms of action of many hypoxia tracers have not been entirely rationalized, especially in the case of metallo-probes. An insight into the hypoxia selectivity mechanisms can allow an optimization of current imaging probes candidates and this will be explored hereby. The mechanistic understanding of the modes of action of coordination compounds under oxygen concentration gradients in living cells allows an expansion of the scope of compounds toward in vivo applications which, in turn, would help translate these into clinical applications. We summarize hereby some of the recent research efforts made toward the discovery of new oxygen sensing molecules having a metal-ligand core. We discuss their applications in vitro and/or in vivo, with an appreciation of a plethora of molecular imaging techniques (mainly reliant on nuclear medicine techniques) currently applied in the detection and tracing of hypoxia in the preclinical and clinical setups. The design of imaging/sensing probe for early-stage diagnosis would longer term avoid invasive procedures providing platforms for therapy monitoring in a variety of NCDs and, particularly, in cancers.
“…Most commercial IMS instruments are limited to resolving powers that are insufficient to separate glycan isomers. With these instruments, alternative methods using the incorporation of metal ions [64–66] and ligands [67,68] have been found to effectively improve the separation of glycan isomers. While most studies of glycan–metal ion complexes focus on the incorporation of a single metal ion [64–66,69], a recent investigation into the optimal metal–ion complexes for different types of glycans found that incorporating multiple metal ions with a single glycan can result in a better separation of the glycan isomers [70].…”
Section: Analytical Strategies Employed For the Chromatographic Separmentioning
Changes in the glycome of human proteins and cells are associated with the progression of multiple diseases such as Alzheimer's, diabetes mellitus, many types of cancer, and those caused by viruses. Consequently, several studies have shown essential modifications to the isomeric glycan moieties for diseases in different stages. However, the elucidation of extensive isomeric glycan profiles remains challenging because of the lack of analytical techniques with sufficient resolution power to separate all glycan and glycopeptide iso‐forms. Therefore, the development of sensitive and accurate approaches for the characterization of all the isomeric forms of glycans and glycopeptides is essential to tracking the progression of pathology in glycoprotein‐related diseases. This review describes the isomeric separation achievements reported in glycomics and glycoproteomics in the last decade. It focuses on the mass spectrometry–based analytical strategies, stationary phases, and derivatization techniques that have been developed to enhance the separation mechanisms in liquid chromatography systems and the detection capabilities of mass spectrometry systems.
“…Therefore, it was proposed that FRET would facilitate the imaging of complex cellular systems in whole live organisms [10]. A new ratiometric two-photon fluorescent probe (RN3) was recently synthesized to detect Palladium 2 + (Pd2 + ) in living zebrafish larvae by FRET, with a significant advantage in monitoring Pd2 + due to that RN3 possessed excellent biocompatibility and low cell cytotoxicity [11].…”
Bio-imaging is a tedious task when it concerns exploring cell functions, developmental mechanisms, and other vital processes in vivo. Single-cell resolution is challenging due to different issues such as sample size, the scattering of intact and opaque tissue, pigmentation in untreated animals, the movement of living organs, and maintaining the sample under physiological conditions. These factors might lead researchers to implement microscopy techniques with a suitable animal model to mimic the nature of the living cells. Zebrafish acquired its prestigious reputation in the biomedical research field due to its transparency under advanced microscopes. Therefore, various microscopy techniques, including Multi-Photon, Light-Sheet Microscopy, and Second Harmonic Generation, simplify the discovery of different types of internal functions in zebrafish. In this review, we briefly discuss three recent microscopy techniques that are being utilized because they are non-invasive in investigating developmental events in zebrafish embryo and larvae.
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