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Article: Blue marine therapy: Sea as a trove of natural anticancer drugs.

Bettio, Delphine / Page, Guylène / Thoreau, Vincent

2023 Volume 81, Issue 6, Page(s) 935–941

Abstract: The great variability of marine habitats and the species that live there allows the development of organisms with unique characteristics. These represent an excellent source of natural compounds and are therefore interesting in the search for new ... ...

Abstract	The great variability of marine habitats and the species that live there allows the development of organisms with unique characteristics. These represent an excellent source of natural compounds and are therefore interesting in the search for new bioactive molecules. In recent years, many marine-based drugs have been commercialized or are currently under investigation, mainly in the treatment of cancer. This mini-review summarizes the marine-based drugs currently marketed and presents a non-exhaustive list of molecules currently in clinical trials, as monotherapy but also in combination with classical anticancer treatments.
Language	English
Publishing date	2023-06-15
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	307-4
ISSN	0003-4509
ISSN	0003-4509
DOI	10.1016/j.pharma.2023.06.001
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Article: Physiologically-based pharmacokinetic models to predict drug exposure during pregnancy.

Ait-Chikh, Celia / Page, Guylène / Thoreau, Vincent

Annales pharmaceutiques francaises

2023 Volume 82, Issue 2, Page(s) 236–242

Abstract: As pregnant women are constantly exposed to drugs during pregnancy, either to treat long-term conditions or acute illnesses, drug safety is a major concern for the fetus and the mother. Clinical trials are rarely made in this population due to strict ... ...

Abstract	As pregnant women are constantly exposed to drugs during pregnancy, either to treat long-term conditions or acute illnesses, drug safety is a major concern for the fetus and the mother. Clinical trials are rarely made in this population due to strict regulation and ethical reasons. However, drug pharmacokinetic (PK) parameters vary during pregnancy with an increase in distribution volume, renal clearance and more. In addition, the fetal distribution should be evaluated with the importance of placental diffusion, both active and passive. Therefore, there is a recent interest in the use of physiologically-based pharmacokinetic (PBPK) modeling to characterize these changes and complete the sparse data available on drug PK during pregnancy. Indeed, PBPK models integrate drug physicochemical and physiological parameters corresponding to each compartment of the body to estimate drug concentrations. This review establishes an overview on the current use of PBPK models in drug dosage determination for the pregnant woman, fetal exposure and drug interactions in the fetal compartment.
MeSH term(s)	Pregnancy ; Female ; Humans ; Placenta ; Models, Biological ; Fetus
Language	English
Publishing date	2023-09-20
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	307-4
ISSN	0003-4509
ISSN	0003-4509
DOI	10.1016/j.pharma.2023.09.005
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Zs.A 223: Show issues

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Article: Brain tumours: Non-invasive techniques to treat invasive pathologies.

Barbotin, Mathis / Thoreau, Vincent / Page, Guylène

Annales pharmaceutiques francaises

2023 Volume 82, Issue 2, Page(s) 229–235

Abstract: Brain and other central nervous system tumours are cancers of poor prognosis, for which current therapeutic possibilities do not match the expectations regarding a curative objective. If the treatment of central nervous system tumours is so difficult, it ...

Abstract	Brain and other central nervous system tumours are cancers of poor prognosis, for which current therapeutic possibilities do not match the expectations regarding a curative objective. If the treatment of central nervous system tumours is so difficult, it is partly due to the blood-brain barrier and the blood-tumour barrier, which need to be crossed to access the tumour. Driven by these insufficient results, more and more techniques and technologies are being explored and are evolving: the progress of surgery and radiotherapy, the growing place of immunotherapies, or the apparition of new non-invasive techniques. The latter are those which interest us here, where promising advances are taking the leap to clinical trials. Nose-to-brain delivery, receptor-mediated transcytosis and micro-bubbles-associated focused ultrasounds are three therapeutic propositions with encouraging results regarding the improvement of drug access to the brain. Even though they might have their share of limits and adverse effects, benefit-risk balance looks promising, and they may appear as new options to treat patients in the future.
MeSH term(s)	Humans ; Brain Neoplasms/therapy ; Brain Neoplasms/drug therapy ; Blood-Brain Barrier
Language	English
Publishing date	2023-10-20
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	307-4
ISSN	0003-4509
ISSN	0003-4509
DOI	10.1016/j.pharma.2023.10.004
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Article ; Online: Identification of Intron Retention in the Slc16a3 Gene Transcript Encoding the Transporter MCT4 in the Brain of Aged and Alzheimer-Disease Model (APPswePS1dE9) Mice.

El-Seedy, Ayman / Pellerin, Luc / Page, Guylène / Ladeveze, Veronique

Genes

2023 Volume 14, Issue 10

Abstract: The monocarboxylate transporter 4 (MCT4; Slc16a3) is expressed in the central nervous system, notably by astrocytes. It is implicated in lactate release and the regulation of glycolytic flux. Whether its expression varies during normal and/or ... ...

Abstract	The monocarboxylate transporter 4 (MCT4; Slc16a3) is expressed in the central nervous system, notably by astrocytes. It is implicated in lactate release and the regulation of glycolytic flux. Whether its expression varies during normal and/or pathological aging is unclear. As the presence of its mature transcript in the brain of young and old mice was determined, an unexpectedly longer RT-PCR fragment was detected in the mouse frontal cortex and hippocampus at 12 vs. 3 months of age. Cultured astrocytes expressed the expected 516 base pair (bp) fragment but treatment with IL-1β to mimic inflammation as can occur during aging led to the additional expression of a 928 bp fragment like that seen in aged mice. In contrast, cultured pericytes (a component of the blood-brain barrier) only exhibited the 516 bp fragment. Intriguingly, cultured endothelial cells constitutively expressed both fragments. When RT-PCR was performed on brain subregions of an Alzheimer mouse model (APPswePS1dE9), no fragment was detected at 3 months, while only the 928 bp fragment was present at 12 months. Sequencing of MCT4 RT-PCR products revealed the presence of a remaining intron between exon 2 and 3, giving rise to the longer fragment detected by RT-PCR. These results unravel the existence of intron retention for the MCT4 gene in the central nervous system. Such alternative splicing appears to increase with age in the brain and might be prominent in neurodegenerative diseases such as Alzheimer's disease. Hence, further studies in vitro and in vivo of intron 2 retention in the Slc16a3 gene transcript are required for adequate characterization concerning the biological roles of Slc16a3 isoforms in the context of aging and Alzheimer's disease pathology.
MeSH term(s)	Animals ; Mice ; Alzheimer Disease/genetics ; Biological Transport ; Brain ; Endothelial Cells ; Introns/genetics
Chemical Substances	Slc16a4 protein, mouse
Language	English
Publishing date	2023-10-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14101949
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Article ; Online: Chronic intraperitoneal injection of polyethylene glycol 200 in mice induces hippocampal neuroinflammation.

Freyssin, Aline / Fauconneau, Bernard / Chassaing, Damien / Rioux Bilan, Agnès / Page, Guylène

Drug and chemical toxicology

2021 Volume 45, Issue 5, Page(s) 1995–2002

Abstract: ... In ... ...

Abstract	In vivo
MeSH term(s)	Animals ; Astrocytes/metabolism ; Glial Fibrillary Acidic Protein/metabolism ; Glial Fibrillary Acidic Protein/pharmacology ; Hippocampus ; Injections, Intraperitoneal ; Mice ; Microglia ; Neuroinflammatory Diseases ; Polyethylene Glycols/toxicity
Chemical Substances	Glial Fibrillary Acidic Protein ; Polyethylene Glycols (3WJQ0SDW1A)
Language	English
Publishing date	2021-03-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	548368-2
ISSN	1525-6014 ; 0148-0545
ISSN (online)	1525-6014
ISSN	0148-0545
DOI	10.1080/01480545.2021.1894738
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Zs.A 1380: Show issues

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Article ; Online: Pro-inflammatory cytokine secretion induced by amyloid transthyretin in human cardiac fibroblasts.

Magaud, Christophe / Harnois, Thomas / Sebille, Stephane / Chatelier, Aurelien / Faivre, Jean-Francois / Bois, Patrick / Page, Guylene / Gellen, Barnabas

Biochemical and biophysical research communications

2022 Volume 642, Page(s) 83–89

Abstract: Extracellular aggregates of wild-type human transthyretin are associated with heart diseases such as wild-type transthyretin (TTR)-derived amyloidosis (ATTR-wt). Due to their strategic location, cardiac fibroblasts act as sentinel cells that sense injury ...

Abstract	Extracellular aggregates of wild-type human transthyretin are associated with heart diseases such as wild-type transthyretin (TTR)-derived amyloidosis (ATTR-wt). Due to their strategic location, cardiac fibroblasts act as sentinel cells that sense injury and activate the inflammasome. No studies of the effects of TTR amyloid aggregation on the secretion of inflammatory factors by primary human cardiac fibroblasts (hCFs) have been reported yet. The intracellular internalization of TTR aggregates, which correspond to the early stage of ATTR-wt, were determined using immunofluorescence and Western blotting of cell lysates. A further objective of this study was to analyze the secretion of inflammatory factors by hCFs after analysis of TTR amyloid aggregation using X-MAP® Luminex Assay techniques. We show that TTR aggregates are internalized in hCFs and induce the secretion of both Brain Natriuretic Peptide (BNP) and N-terminal pro B-type Natriuretic Peptide(NT-proBNP). Also, pro-inflammatory mediators such as interleukin-6 (IL-6) and IL-8 are secreted without significant changes in the levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). In conclusion, these findings suggest that IL-6 and IL-8 play important roles in the development of ATTR-wt, and indicate that IL-6 in particular could be a potentially important therapeutic target in patients with ATTR-wt.
MeSH term(s)	Humans ; Prealbumin ; Interleukin-6 ; Interleukin-8 ; Amyloid Neuropathies, Familial/drug therapy ; Amyloid ; Fibroblasts
Chemical Substances	Prealbumin ; Interleukin-6 ; Interleukin-8 ; Amyloid
Language	English
Publishing date	2022-12-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2022.12.027
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Zs.A 116: Show issues

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Article: Natural stilbenes effects in animal models of Alzheimer's disease.

Freyssin, Aline / Page, Guylène / Fauconneau, Bernard / Rioux Bilan, Agnès

Neural regeneration research

2019 Volume 15, Issue 5, Page(s) 843–849

Abstract: Alzheimer's disease is one of the most frequent neurodegenerative diseases. This pathology is characterized by protein aggregates, mainly constituted by amyloid peptide and tau, leading to neuronal death and cognitive impairments. Drugs currently ... ...

Abstract	Alzheimer's disease is one of the most frequent neurodegenerative diseases. This pathology is characterized by protein aggregates, mainly constituted by amyloid peptide and tau, leading to neuronal death and cognitive impairments. Drugs currently proposed to treat this pathology do not prevent neurodegenerative processes and are mainly symptomatic therapies. However, stilbenes presenting multiple pharmacological effects could be good potential therapeutic candidates. The aim of this review is to gather the more significant papers among the broad literature on this topic, concerning the beneficial effects of stilbenes (resveratrol derivatives) in animal models of Alzheimer's disease. Indeed, numerous studies focus on cellular models, but an in vivo approach remains of primary importance since in animals (mice or rats, generally), bioavailability and metabolism are taken into account, which is not the case in in vitro studies. Furthermore, examination of memory ability is feasible in animal models, which strengthens the relevance of a compound with a view to future therapy in humans. This paper is addressed to any researcher who needs to study untested natural stilbenes or who wants to experiment the most effective natural stilbenes in largest animals or in humans. This review shows that resveratrol, the reference polyphenol, is largely studied and seems to have interesting properties on amyloid plaques, and cognitive impairment. However, some resveratrol derivatives such as gnetin C, trans-piceid, or astringin have never been tested on animals. Furthermore, pterostilbene is of particular interest, by its improvement of cognitive disorders and its neuroprotective role. It could be relevant to evaluate this molecule in clinical trials.
Language	English
Publishing date	2019-11-12
Publishing country	India
Document type	Journal Article ; Review
ZDB-ID	2388460-5
ISSN	1876-7958 ; 1673-5374
ISSN (online)	1876-7958
ISSN	1673-5374
DOI	10.4103/1673-5374.268970
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Article: Natural polyphenols effects on protein aggregates in Alzheimer's and Parkinson's prion-like diseases.

Freyssin, Aline / Page, Guylène / Fauconneau, Bernard / Rioux Bilan, Agnès

Neural regeneration research

2018 Volume 13, Issue 6, Page(s) 955–961

Abstract: Alzheimer's and Parkinson's diseases are the most common neurodegenerative diseases. They are characterized by protein aggregates and so can be considered as prion-like disease. The major components of these deposits are amyloid peptide and tau for ... ...

Abstract	Alzheimer's and Parkinson's diseases are the most common neurodegenerative diseases. They are characterized by protein aggregates and so can be considered as prion-like disease. The major components of these deposits are amyloid peptide and tau for Alzheimer's disease, α-synuclein and synphilin-1 for Parkinson's disease. Drugs currently proposed to treat these pathologies do not prevent neurodegenerative processes and are mainly symptomatic therapies. Molecules inducing inhibition of aggregation or disaggregation of these proteins could have beneficial effects, especially if they have other beneficial effects for these diseases. Thus, several natural polyphenols, which have antioxidative, anti-inflammatory and neuroprotective properties, have been largely studied, for their effects on protein aggregates found in these diseases, notably in vitro. In this article, we propose to review the significant papers concerning the role of polyphenols on aggregation and disaggregation of amyloid peptide, tau, α-synuclein, synphilin-1, suggesting that these compounds could be useful in the treatments in Alzheimer's and Parkinson's diseases.
Language	English
Publishing date	2018-06-19
Publishing country	India
Document type	Journal Article ; Review
ZDB-ID	2388460-5
ISSN	1876-7958 ; 1673-5374
ISSN (online)	1876-7958
ISSN	1673-5374
DOI	10.4103/1673-5374.233432
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Article ; Online: Differential chemokine expression under the control of peripheral blood mononuclear cells issued from Alzheimer's patients in a human blood brain barrier model.

Vérité, Julie / Page, Guylène / Paccalin, Marc / Julian, Adrien / Janet, Thierry

PloS one

2018 Volume 13, Issue 8, Page(s) e0201232

Abstract: Growing evidence highlights the peripheral blood mononuclear cells (PBMCs) role and the chemokine involvement in the Alzheimer's disease (AD) physiopathology. However, few data are available about the impact of AD PBMCs in the chemokine signature in a ... ...

Abstract	Growing evidence highlights the peripheral blood mononuclear cells (PBMCs) role and the chemokine involvement in the Alzheimer's disease (AD) physiopathology. However, few data are available about the impact of AD PBMCs in the chemokine signature in a brain with AD phenotype. Therefore, this study analyzed the chemokine levels in a human blood brain barrier model. A human endothelial cell line from the immortalized cerebral microvascular endothelial cell line (hCMEC/D3) and a human glioblastoma U-87 MG cell line, both with no AD phenotype were used while PBMCs came from AD at mild or moderate stage and control patients. PBMCs from moderate AD patients decreased CCL2 and CCL5 levels in endothelial, and also CXCL10 in abluminal compartments and in PBMCs compared to PBMCs from mild AD patients. The CX3CL1 expression increased in endothelial and abluminal compartments with PBMCs from mild AD patients compared to controls. AD PBMCs can convert the chemokine signature towards that found in AD brain, targeting some chemokines as new biomarkers in AD.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/blood ; Alzheimer Disease/diagnosis ; Alzheimer Disease/physiopathology ; Biomarkers/blood ; Blood-Brain Barrier/immunology ; Blood-Brain Barrier/physiopathology ; Case-Control Studies ; Cell Line ; Chemokine CCL2/blood ; Chemokine CCL4/blood ; Chemokine CCL5/blood ; Chemokine CX3CL1/blood ; Chemokine CXCL10/blood ; Chemokines/blood ; Chemokines/immunology ; Coculture Techniques ; Female ; Humans ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Male ; Models, Neurological
Chemical Substances	Biomarkers ; CCL2 protein, human ; CCL4 protein, human ; CCL5 protein, human ; CX3CL1 protein, human ; CXCL10 protein, human ; Chemokine CCL2 ; Chemokine CCL4 ; Chemokine CCL5 ; Chemokine CX3CL1 ; Chemokine CXCL10 ; Chemokines
Language	English
Publishing date	2018-08-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0201232
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Article: Trans

Freyssin, Aline / Rioux Bilan, Agnès / Fauconneau, Bernard / Galineau, Laurent / Serrière, Sophie / Tauber, Clovis / Perrin, Flavie / Guillard, Jérôme / Chalon, Sylvie / Page, Guylène

Frontiers in neuroscience

2022 Volume 15, Page(s) 803927

Abstract: In a previous study, we showed that viniferin decreased amyloid deposits and reduced neuroinflammation in APPswePS1dE9 transgenic mice between 3 and 6 months of age. In the present study, wild type and APPswePS1dE9 transgenic mice were treated from 7 to ... ...

Abstract	In a previous study, we showed that viniferin decreased amyloid deposits and reduced neuroinflammation in APPswePS1dE9 transgenic mice between 3 and 6 months of age. In the present study, wild type and APPswePS1dE9 transgenic mice were treated from 7 to 11 or from 3 to 12 months by a weekly intraperitoneal injection of either 20 mg/kg viniferin or resveratrol or their vehicle, the polyethylene glycol 200 (PEG 200). The cognitive status of the mice was evaluated by the Morris water maze test. Then, amyloid burden and neuroinflammation were quantified by western-blot, Enzyme-Linked ImmunoSorbent Assay (ELISA), immunofluorescence, and
Language	English
Publishing date	2022-01-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2021.803927
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