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Open AccessEditor’s ChoiceArticle

ACE2 Protein Landscape in the Head and Neck Region: The Conundrum of SARS-CoV-2 Infection

by Géraldine Descamps, Laurine Verset, Anne Trelcat, Claire Hopkins, Jérome R. Lechien, Fabrice Journe and Sven Saussez

Biology 2020, 9(8), 235; https://doi.org/10.3390/biology9080235 - 18 Aug 2020

Cited by 42 | Viewed by 4854

Abstract

The coronavirus pandemic raging worldwide since December 2019 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which invades human cells via the angiotensin-converting enzyme 2 (ACE2) receptor. Although it has already been identified in many organs, ACE2 expression remains largely [...] Read more.

The coronavirus pandemic raging worldwide since December 2019 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which invades human cells via the angiotensin-converting enzyme 2 (ACE2) receptor. Although it has already been identified in many organs, ACE2 expression remains largely unknown in the head and neck (HN) sphere. Thus, this study aims to investigate its protein expression in several sites of the upper aerodigestive tract in order to highlight potential routes of infection. We compared ACE2 immunohistochemical expression between 70 paraffin-embedded specimens with two different antibodies and reported the quantified expression in each histological location. Surprisingly, we obtained different results depending on the antibody, an absence of labeling having been observed with a monoclonal antibody raised against the extracellular domain, whereas the polyclonal, against the cytoplasmic part of the protein, revealed enriched ACE2 expression, particularly in sinuses, vocal cords, salivary glands and oral cavity epithelial cells. The interpretation of these discordant results has brought several exciting lines of reflection. In conclusion, this study provides possible routes of entry for the SARS-CoV-2 in HN region and, above all, has led us to encourage caution when studying the ACE2 expression which is currently at the center of all attention. Full article

(This article belongs to the Special Issue Molecular Targets and Targeting in Biomedical Sciences)

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16 pages, 2711 KiB

Open AccessArticle

Toad Venom Antiproliferative Activities on Metastatic Melanoma: Bio-Guided Fractionation and Screening of the Compounds of Two Different Venoms

by Laura Soumoy, Mathilde Wells, Ahmad Najem, Mohammad Krayem, Ghanem Ghanem, Stéphanie Hambye, Sven Saussez, Bertrand Blankert and Fabrice Journe

Biology 2020, 9(8), 218; https://doi.org/10.3390/biology9080218 - 10 Aug 2020

Cited by 9 | Viewed by 3139

Abstract

Melanoma is the most common cancer in young adults, with a constantly increasing incidence. Metastatic melanoma is a very aggressive cancer with a 5-year survival rate of about 22−25%. This is, in most cases, due to a lack of therapies which are effective [...] Read more.

Melanoma is the most common cancer in young adults, with a constantly increasing incidence. Metastatic melanoma is a very aggressive cancer with a 5-year survival rate of about 22−25%. This is, in most cases, due to a lack of therapies which are effective on the long term. Hence, it is crucial to find new therapeutic agents to increase patient survival. Toad venoms are a rich source of potentially pharmaceutically active compounds and studies have highlighted their possible effect on cancer cells. We focused on the venoms of two different toad species: Bufo bufo and Rhinella marina. We screened the venom crude extracts, the fractions from crude extracts and isolated biomolecules by studying their antiproliferative properties on melanoma cells aiming to determine the compound or the combination of compounds with the highest antiproliferative effect. Our results indicated strong antiproliferative capacities of toad venoms on melanoma cells. We found that these effects were mainly due to bufadienolides that are cardiotonic steroids potentially acting on the Na⁺/K⁺ ATPase pump which is overexpressed in melanoma. Finally, our results indicated that bufalin alone was the most interesting compound among the isolated bufadienolides because it had the highest antiproliferative activity on melanoma cells. Full article

(This article belongs to the Special Issue Molecular Targets and Targeting in Biomedical Sciences)

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26 pages, 5157 KiB

Open AccessArticle

Development of an LDL Receptor-Targeted Peptide Susceptible to Facilitate the Brain Access of Diagnostic or Therapeutic Agents

by Séverine André, Lionel Larbanoix, Sébastien Verteneuil, Dimitri Stanicki, Denis Nonclercq, Luce Vander Elst, Sophie Laurent, Robert N. Muller and Carmen Burtea

Biology 2020, 9(7), 161; https://doi.org/10.3390/biology9070161 - 11 Jul 2020

Cited by 13 | Viewed by 4211

Abstract

Blood-brain barrier (BBB) crossing and brain penetration are really challenging for the delivery of therapeutic agents and imaging probes. The development of new crossing strategies is needed, and a wide range of approaches (invasive or not) have been proposed so far. The receptor-mediated [...] Read more.

Blood-brain barrier (BBB) crossing and brain penetration are really challenging for the delivery of therapeutic agents and imaging probes. The development of new crossing strategies is needed, and a wide range of approaches (invasive or not) have been proposed so far. The receptor-mediated transcytosis is an attractive mechanism, allowing the non-invasive penetration of the BBB. Among available targets, the low-density lipoprotein (LDL) receptor (LDLR) shows favorable characteristics mainly because of the lysosome-bypassed pathway of LDL delivery to the brain, allowing an intact discharge of the carried ligand to the brain targets. The phage display technology was employed to identify a dodecapeptide targeted to the extracellular domain of LDLR (ED-LDLR). This peptide was able to bind the ED-LDLR in the presence of natural ligands and dissociated at acidic pH and in the absence of calcium, in a similar manner as the LDL. In vitro, our peptide was endocytosed by endothelial cells through the caveolae-dependent pathway, proper to the LDLR route in BBB, suggesting the prevention of its lysosomal degradation. The in vivo studies performed by magnetic resonance imaging and fluorescent lifetime imaging suggested the brain penetration of this ED-LDLR-targeted peptide. Full article

(This article belongs to the Special Issue Molecular Targets and Targeting in Biomedical Sciences)

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19 pages, 1934 KiB

Open AccessArticle

A Comparative Study of Rat Urine ¹H-NMR Metabolome Changes Presumably Arising from Isoproterenol-Induced Heart Necrosis Versus Clarithromycin-Induced QT Interval Prolongation

by Matthieu Dallons, Manon Delcourt, Corentin Schepkens, Manuel Podrecca and Jean-Marie Colet

Biology 2020, 9(5), 98; https://doi.org/10.3390/biology9050098 - 13 May 2020

Cited by 1 | Viewed by 4231

Abstract

Cardiotoxicity remains a challenging concern both in drug development and in the management of various clinical situations. There are a lot of examples of drugs withdrawn from the market or stopped during clinical trials due to unpredicted cardiac adverse events. Obviously, current conventional [...] Read more.

Cardiotoxicity remains a challenging concern both in drug development and in the management of various clinical situations. There are a lot of examples of drugs withdrawn from the market or stopped during clinical trials due to unpredicted cardiac adverse events. Obviously, current conventional methods for cardiotoxicity assessment suffer from a lack of predictivity and sensitivity. Therefore, there is a need for developing new tools to better identify and characterize any cardiotoxicity that can occur during the pre-clinical and clinical phases of drug development as well as after marketing in exposed patients. In this study, isoproterenol and clarithromycin were used as prototypical cardiotoxic agents in rats in order to evaluate potential biomarkers of heart toxicity at very early stages using ¹H-NMR-based metabonomics. While isoproterenol is known to cause heart necrosis, clarithromycin may induce QT interval prolongation. Heart necrosis and QT prolongation were validated by histological analysis, serum measurement of lactate dehydrogenase/creatine phosphate kinase and QTc measurement by electrocardiogram (ECG). Urine samples were collected before and repeatedly during daily exposure to the drugs for ¹H-NMR based-metabonomics investigations. Specific metabolic signatures, characteristic of each tested drug, were obtained from which potential predictive biomarkers for drug-induced heart necrosis and drug-induced QT prolongation were retrieved. Isoproterenol-induced heart necrosis was characterized by higher levels of taurine, creatine, glucose and by lower levels of Krebs cycle intermediates, creatinine, betaine/trimethylamine N-oxide (TMAO), dimethylamine (DMA)/sarcosine. Clarithromycin-induced QT prolongation was characterized by higher levels of creatinine, taurine, betaine/TMAO and DMA/sarcosine and by lower levels of Krebs cycle intermediates, glucose and hippurate. Full article

(This article belongs to the Special Issue Molecular Targets and Targeting in Biomedical Sciences)

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25 pages, 8085 KiB

Open AccessArticle

Molecular Imaging of Galectin-1 Expression as a Biomarker of Papillary Thyroid Cancer by Using Peptide-Functionalized Imaging Probes

by Deborah Fanfone, Dimitri Stanicki, Denis Nonclercq, Marc Port, Luce Vander Elst, Sophie Laurent, Robert N. Muller, Sven Saussez and Carmen Burtea

Biology 2020, 9(3), 53; https://doi.org/10.3390/biology9030053 - 14 Mar 2020

Cited by 7 | Viewed by 3755

Abstract

Thyroid cancers are the most frequent endocrine cancers and their incidence is increasing worldwide. Thyroid nodules occur in over 19–68% of the population, but only 7–15% of them are diagnosed as malignant. Diagnosis relies on a fine needle aspiration biopsy, which is often [...] Read more.

Thyroid cancers are the most frequent endocrine cancers and their incidence is increasing worldwide. Thyroid nodules occur in over 19–68% of the population, but only 7–15% of them are diagnosed as malignant. Diagnosis relies on a fine needle aspiration biopsy, which is often inconclusive and about 90% of thyroidectomies are performed for benign lesions. Galectin-1 has been proposed as a confident biomarker for the discrimination of malignant from benign nodules. We previously identified by phage display two peptides (P1 and P7) targeting galectin-1, with the goal of developing imaging probes for non-invasive diagnosis of thyroid cancer. The peptides were coupled to ultra-small superparamagnetic particles of iron oxide (USPIO) or to a near-infrared dye (CF770) for non-invasive detection of galectin-1 expression in a mouse model of papillary thyroid cancer (PTC, as the most frequent one) by magnetic resonance imaging and fluorescence lifetime imaging. The imaging probes functionalized with the two peptides presented comparable image enhancement characteristics. However, those coupled to P7 were more favorable, and showed decreased retention by the liver and spleen (known for their galectin-1 expression) and high sensitivity (75%) and specificity (100%) of PTC detection, which confirm the aptitude of this peptide to discriminate human malignant from benign nodules (80% sensitivity, 100% specificity) previously observed by immunohistochemistry. Full article

(This article belongs to the Special Issue Molecular Targets and Targeting in Biomedical Sciences)

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Review

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22 pages, 2956 KiB

Open AccessReview

VCAM-1 Target in Non-Invasive Imaging for the Detection of Atherosclerotic Plaques

by Kathleen Thayse, Nadège Kindt, Sophie Laurent and Stéphane Carlier

Biology 2020, 9(11), 368; https://doi.org/10.3390/biology9110368 - 29 Oct 2020

Cited by 41 | Viewed by 7391

Abstract

Atherosclerosis is a progressive chronic arterial disease characterised by atheromatous plaque formation in the intima of the arterial wall. Several invasive and non-invasive imaging techniques have been developed to detect and characterise atherosclerosis in the vessel wall: anatomic/structural imaging, functional imaging and molecular [...] Read more.

Atherosclerosis is a progressive chronic arterial disease characterised by atheromatous plaque formation in the intima of the arterial wall. Several invasive and non-invasive imaging techniques have been developed to detect and characterise atherosclerosis in the vessel wall: anatomic/structural imaging, functional imaging and molecular imaging. In molecular imaging, vascular cell adhesion molecule-1 (VCAM-1) is a promising target for the non-invasive detection of atherosclerosis and for the assessment of novel antiatherogenic treatments. VCAM-1 is an adhesion molecule expressed on the activated endothelial surface that binds leucocyte ligands and therefore promotes leucocyte adhesion and transendothelial migration. Hence, for several years, there has been an increase in molecular imaging methods for detecting VCAM-1 in MRI, PET, SPECT, optical imaging and ultrasound. The use of microparticles of iron oxide (MPIO), ultrasmall superparamagnetic iron oxide (USPIO), microbubbles, echogenic immunoliposomes, peptides, nanobodies and other nanoparticles has been described. However, these approaches have been tested in animal models, and the remaining challenge is bench-to-bedside development and clinical applicability. Full article

(This article belongs to the Special Issue Molecular Targets and Targeting in Biomedical Sciences)

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28 pages, 8206 KiB

Open AccessReview

Liposome-Based Bioassays

by Jacopo Sforzi, Lorenzo Palagi and Silvio Aime

Biology 2020, 9(8), 202; https://doi.org/10.3390/biology9080202 - 1 Aug 2020

Cited by 25 | Viewed by 11387

Abstract

This review highlights the potential of using liposomes in bioassays. Liposomes consist of nano- or micro-sized, synthetically constructed phospholipid vesicles. Liposomes can be loaded with a number of reporting molecules that allow a dramatic amplification of the detection threshold in bioassays. Liposome-based sensors [...] Read more.

This review highlights the potential of using liposomes in bioassays. Liposomes consist of nano- or micro-sized, synthetically constructed phospholipid vesicles. Liposomes can be loaded with a number of reporting molecules that allow a dramatic amplification of the detection threshold in bioassays. Liposome-based sensors bind or react with the biological components of targets through the introduction of properly tailored vectors anchored on their external surface. The use of liposome-based formulations allows the set-up of bioassays that are rapid, sensitive, and often suitable for in-field applications. Selected applications in the field of immunoassays, as well as recognition/assessment of corona proteins, nucleic acids, exosomes, bacteria, and viruses are surveyed. The role of magnetoliposomes is also highlighted as an additional tool in the armory of liposome-based systems for bioassays. Full article

(This article belongs to the Special Issue Molecular Targets and Targeting in Biomedical Sciences)

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13 pages, 936 KiB

Open AccessReview

Lymphocyte-Activation Gene 3 (LAG3) Protein as a Possible Therapeutic Target for Parkinson’s Disease: Molecular Mechanisms Connecting Neuroinflammation to α-Synuclein Spreading Pathology

by Efthalia Angelopoulou, Yam Nath Paudel, Chiara Villa, Mohd. Farooq Shaikh and Christina Piperi

Biology 2020, 9(4), 86; https://doi.org/10.3390/biology9040086 - 23 Apr 2020

Cited by 24 | Viewed by 7047

Abstract

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder without any objective biomarker available to date. Increasing evidence highlights the critical role of neuroinflammation, including T cell responses, and spreading of aggregated α-synuclein in PD progression. Lymphocyte-activation gene 3 (LAG3) belongs to [...] Read more.

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder without any objective biomarker available to date. Increasing evidence highlights the critical role of neuroinflammation, including T cell responses, and spreading of aggregated α-synuclein in PD progression. Lymphocyte-activation gene 3 (LAG3) belongs to the immunoglobulin (Ig) superfamily expressed by peripheral immune cells, microglia and neurons and plays a key role in T cell regulation. The role of LAG3 has been extensively investigated in several human cancers, whereas until recently, the role of LAG3 in the central nervous system (CNS) has been largely unknown. Accumulating evidence highlights the potential role of LAG3 in PD pathogenesis, mainly by binding to α-synuclein fibrils and affecting its endocytosis and intercellular transmission, which sheds more light on the connection between immune dysregulation and α-synuclein spreading pathology. Serum and cerebrospinal fluid (CSF) soluble LAG3 (sLAG3) levels have been demonstrated to be potentially associated with PD development and clinical phenotype, suggesting that sLAG3 could represent an emerging PD biomarker. Specific single nucleotide polymorphisms (SNPs) of the LAG3 gene have been also related to PD occurrence especially in the female population, enlightening the pathophysiological background of gender-related PD clinical differences. Given also the ongoing clinical trials investigating various LAG3-targeting strategies in human diseases, new opportunities are being developed for PD treatment research. In this review, we discuss recent preclinical and clinical evidence on the role of LAG3 in PD pathogenesis and biomarker potential, aiming to elucidate its underlying molecular mechanisms. Full article

(This article belongs to the Special Issue Molecular Targets and Targeting in Biomedical Sciences)

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