Sylvain Chemtob

Sylvain Chemtob
CHU Sainte-Justine · Department of Paediatric

About

427
Publications
29,859
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13,258
Citations
Citations since 2016
121 Research Items
4821 Citations
20162017201820192020202120220200400600
20162017201820192020202120220200400600
20162017201820192020202120220200400600
20162017201820192020202120220200400600
Introduction

Publications

Publications (427)
Article
Background: Preterm birth is the leading cause of neonatal morbidity and mortality. Studies have shown that interleukin-1 plays a major role in the pathophysiology of preterm birth participating by inducing the production of pro-inflammatory mediators and uterine activating proteins leading to labor. More importantly, uteroplacental inflammation,...
Article
In pursuit of more effective labor delaying tocolytic agents, the prostaglandin F2α (PGF2α) receptor (FP) modulator PDC113.824 [(6S)‐2] represents a potent lead for developing therapy to treat preterm birth. Derivatives of FP modulator (6S)‐2 were synthesized possessing respectively 5‐ and 7‐hydroxyl groups on the indolizidin‐2‐one amino acid (I2aa...
Preprint
The involvement of G-Protein-Coupled Receptors (GPCR) location bias in diverse cellular functions and their misregulation in pathology is an underexplored territory. HCAR1, a GPCR for lactate is linked to cancer progression, mainly due to Warburg effect, but its mechanism of action remains elusive. Here, we show HCAR1 has a nuclear localization, ca...
Article
Full-text available
The GPCR SUCNR1/GPR91 exerts proangiogenesis upon stimulation with the Krebs cycle metabolite succinate. GPCR signaling depends on the surrounding environment and intracellular localization through location bias. Here, we show by microscopy and by cell fractionation that in neurons, SUCNR1 resides at the endoplasmic reticulum (ER), while being full...
Article
Introduction: G-Protein Coupled Receptors (GPCR) are virtually involved in all physiological processes. HCAR1 (GPR81), as a GPCR, is endogenously activated by lactate and has been shown to promote cancer malignancy via higher level of glycolysis due to Warburg effect. Its expression level is highly elevated in many cancers and negatively correlate...
Article
Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness in the elderly worldwide. Wet AMD is characterized by pathologic choroidal neovascularization that invades the RPE and compromises retinal function. Although anti-vascular endothelial growth factor (anti-VEGF) therapy has been shown to improve symptoms of...
Article
Full-text available
Neutrophils and other leukocytes invade the mouse uterus at term birth, which is normal for activating the uterus for labor. To better understand the regulation of this migration at term and interleukin (IL)-1β—induced preterm birth, we developed a mouse leukocyte migration assay (mLMA) and used it with rytvela, an IL-1 receptor allosteric antagoni...
Article
Retinopathy of prematurity (ROP) may have long-term consequences. We studied the visual function of young adults born prematurely; ROP was associated with a lower visual acuity and a reduced contrast sensitivity.
Article
Introduction: Inflammation-induced white matter injury (WMI) in preterm infants is characterized by microglia activation, astrogliosis, oxidative stress and neurodevelopmental impairments. Microglia and astrocytes activation can be described under a broad spectrum of activation profile with extremes described as pro-inflammatory/neurotoxic (M1 mic...
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Dyslipidemia and autophagy have been implicated in the pathogenesis of blinding neovascular age-related macular degeneration (NV-AMD). Very low-density lipoprotein receptor (VLDLR), expressed in photoreceptors with a high metabolic rate, facilitates the uptake of triglyceride-derived fatty acids (FA). Since FA uptake is reduced in Vldlr-/- tissues,...
Article
Perinatal hypoxic/ischemic (HI) brain injury is a major clinical problem with devastating neurodevelopmental outcomes in neonates. During HI brain injury, dysregulated factor production contributes to microvascular impairment. Glycolysis-derived lactate accumulated during ischemia has been proposed to protect against ischemic injury, but its mechan...
Article
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Purpose: The purpose of this study was to develop an in vivo optical coherence tomography (OCT) system capable of imaging the developing mouse retina and its associated morphometric and microstructural changes. Methods: Thirty-four wild-type mice (129S1/SvlmJ) were anesthetized and imaged between postnatal (P) day 7 and P21. OCT instrumentation...
Article
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Background Intraamniotic inflammation is associated with up to 40% of preterm births, most notably in deliveries occurring prior to 32 weeks’ gestation. Despite this, there are few treatment options allowing the prevention of preterm birth and associated fetal injury. Recent studies have shown that the small, non-competitive allosteric interleukin...
Article
Full-text available
In preparation for delivery, the uterus transitions from actively maintaining quiescence during pregnancy to an active parturient state. This transition occurs as a result of the accumulation of pro-inflammatory signals which are amplified by positive feedback interactions involving paracrine and autocrine signaling at the level of each intrauterin...
Article
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During the development of the retina and the nervous system, high levels of energy are required by the axons of retinal ganglion cells (RGCs) to grow towards their brain targets. This energy demand leads to an increase of glycolysis and L-lactate concentrations in the retina. L-lactate is known to be the endogenous ligand of the GPR81 receptor. How...
Article
Full-text available
Preterm birth (PTB) remains the leading cause of infant morbidity and mortality. Despite 50 years of research, therapeutic options are limited and many lack clear efficacy. Tocolytic agents are drugs that briefly delay PTB, typically to allow antenatal corticosteroid administration for accelerating fetal lung maturity or to transfer patients to hig...
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Aim To explore the current literature on prenatal inflammation-associated risk factors for retinopathy of prematurity (ROP). Methods Subjective summary of selected experimental and epidemiological publications that support the authors’ central hypothesis that the etiology of ROP begins before birth. Results Based on current evidence we suggest th...
Article
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Background and Aim Insufficient post-ischemic neovascularization is an initial key step in the pathogenesis of Oxygen-Induced Retinopathy (OIR). During neovascularization, pro-angiogenic cells (PACs) are mobilized from the bone marrow and integrate into ischemic tissues to promote angiogenesis. However, the modulation of PAC paracrine activity duri...
Article
Preterm birth (PTB) and its consequences are a major public health concern as preterm delivery is the main cause of mortality and morbidity at birth. There are many causes of PTB, but inflammation is undeniably associated with the process of premature childbirth and fetal injury. At present, treatments clinically available mostly involve attempt to...
Article
Full-text available
Ischemic retinopathies (IRs), such as retinopathy of prematurity and diabetic retinopathy, are characterized by an initial phase of microvascular degeneration that results in retinal ischemia, followed by exaggerated pathologic neovascularization (NV). Mesenchymal stromal cells (MSCs) have potent pro-angiogenic and anti-inflammatory properties asso...
Article
Traumatic brain injury is one of the leading causes of morbidity and mortality throughout the world. Its increasing incidence, in addition to its fundamental role in the development of neurodegenerative disease, proves especially concerning. Despite extensive preclinical and clinical studies, researchers have yet to identify a safe and effective ne...
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As a key cytokine mediator of inflammation, interleukin-1β (IL-1β) binds to the IL-1 receptor (IL-1R) and activates various downstream signaling mediators, including NF-κB, which is required for immune vigilance and cellular protection. Toward the development of IL-1-targeting therapeutics which exhibit functional selectivity, the all-D-amino acid...
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The coronavirus disease 2019 (COVID-19) pandemic has become the number one health problem worldwide. As of August 2020, it has affected more than 18 million humans and caused over 700,000 deaths worldwide. COVID-19 is an infectious disease that can lead to severe acute respiratory syndrome. Under certain circumstances, the viral infection leads to...
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Background Inflammation and particularly interleukin-1β (IL-1β), a pro-inflammatory cytokine highly secreted by activated immune cells during early AMD pathological events, contribute significantly to retinal neurodegeneration. Here, we identify specific cell types that generate IL-1β and harbor the IL-1 receptor (IL-1R) and pharmacologically valid...
Article
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GPCRs are the largest receptor family that are involved in virtually all biological processes. Pharmacologically, they are highly druggable targets, as they cover more than 40% of all drugs in the market. Our knowledge of biased signaling provided insight into pharmacology vastly improving drug design to avoid unwanted effects and achieve higher ef...
Article
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The blood–brain barrier (BBB) is a major obstacle to the development of effective diagnostics and therapeutics for brain cancers and other central nervous system diseases. Peptide agonist analogs of kinin B1 and B2 receptors, acting as BBB permeabilizers, have been utilized to overcome this barrier. The purpose of the study was to provide new insig...
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Background Classical cardiovascular risk factors (CRFs) are associated with impaired angiogenic activities of bone marrow–derived proangiogenic cells (PACs) related to peripheral artery diseases (PADs) and ischemia-induced neovascularization. MicroRNAs (miRs) are key regulators of gene expression, and they are involved in the modulation of PAC func...
Article
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The innovative development of azapeptide analogues of growth hormone releasing peptide-6 (GHRP-6) has produced selective modulators of the cluster of differentiation 36 receptor (CD36). The azapeptide CD36 modulators curb macrophage-driven inflammation and mitigate atherosclerotic and angiogenic pathology. In macrophages activated with Toll-like re...
Conference Paper
https://www.gotostage.com/channel/6e18e489a7ba4eabbc2d372c93c09318/recording/ea833141a0ff4a1a953dcef81e35505d/watch?source=CHANNEL&fbclid=IwAR3WeygRrlmc10VxGZzV80CvdFpSW-OfwLngP844nO53Xav3vsr_EC7fzzU
Article
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Retinopathy of prematurity (ROP) is the leading cause of blindness in neonates. Inflammation, in particular interleukin-1β (IL-1β), is increased in early stages of the disorder, and contributes to inner and outer retinal vasoobliteration in the oxygen-induced retinopathy (OIR) model of ROP. A small peptide antagonist of IL-1 receptor, composed of t...
Article
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Background and aims: Vascular degeneration is a hallmark in the pathogenesis of oxygen-induced retinopathy (OIR). Dysregulation of microRNAs (miRNAs), key regulators of genes expressions, has been implicated in the regulation of ocular angiogenesis. However, miRNAs specific functions in impaired vascular development during OIR are poorly understoo...
Article
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Background: CD36, a member of the class B scavenger receptor family, participates in Toll-like receptor signaling on mononuclear phagocytes (MP) and can promote sterile pathogenic inflammation. We here analyzed the effect of CD36 deficiency on retinal inflammation and photoreceptor degeneration, the hallmarks of age-related macular degeneration (AM...
Article
Dynamic chirality influences numerous processes in nature from protein folding to catalysis. Azapeptides are peptidomimetics possessing semicarbazide residues that can interconvert between sp2 and sp3 hybridization, resulting in stereo-dynamic interconversions of pseudo-R and -S-configurations by way of a planar intermediate. Cyclic azapeptides hav...
Article
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N-Alkylation and N-acylation of the prostaglandin-F2α allosteric modulator l-PDC31 were performed to install various alkyl, PEG and isoprenoid groups onto the l-enantiomer of the peptide. Among the different bio-conjugates studied, the N-dodecyl analog reduced prostaglandin-F2α-induced mouse myometrium contractions ex vivo. Furthermore, N-dodecyl-l...
Article
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Purpose: Targeting β-adrenergic receptor signaling with propranolol has emerged as a potential candidate to counteract choroidal neovascularization (CNV). Little is known of its effect on macrophages, which play a critical role in CNV. We investigated the effect of propranolol on angiogenic response of mononuclear phagocytes (MPs). Methods: The...
Article
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In subretinal inflammation, activated mononuclear phagocytes (MP) play a key role in the progression of retinopathies. Little is known about the mechanism involved in the loss of photoreceptors leading to vision impairment. Studying retinal damage induced by photo-oxidative stress, we observed that cluster of differentiation 36 (CD36)-deficient mic...
Article
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Retinopathy of prematurity (ROP) is characterized by an initial retinal avascularization, followed by pathologic neovascularization. Recently, choroidal thinning has also been detected in children formerly diagnosed with ROP; a similar sustained choroidal thinning is observed in ROP models. But the mechanism underlying the lack of choroidal revascu...
Article
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Background Ischemic retinopathies (IRs) are leading causes of visual impairment. They are characterized by an initial phase of microvascular degeneration and a second phase of aberrant pre-retinal neovascularization (NV). microRNAs (miRNAs) regulate gene expression, and a number play a role in normal and pathological NV. But, post-transcriptional m...
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Full text available: https://www.sciencedirect.com/science/article/pii/S0002944018311179?dgcid=coauthor Ischemic retinopathies (IRs) are characterized by a progressive microvascular degeneration followed by a post-ischemic aberrant neovascularization. To reinstate vascular supply and metabolic equilibrium to the ischemic tissue during IRs, a dysreg...
Article
Peptide mimicry employing a combination of aza-amino acyl proline and indolizidinone residues has been used to develop allosteric modulators of the prostaglandin F2α receptor. Systematic study of the N-terminal phenylacetyl moiety, and the conformation and side chain functions of the central turn dipeptide residue has demonstrated the sensitive rel...
Article
Full-text available
Interleukin-1β (IL-1β) binds to the IL-1 receptor (IL-1R) and is a key cytokine mediator of inflammasome activation. IL-1β signaling leads to parturition in preterm birth (PTB) and contributes to the retinal vaso-obliteration characteristic of oxygen-induced retinopathy (OIR) of premature infants. Therapeutics targeting IL-1β and IL-1R are approved...
Article
Complex cellular and physiological interactions are required to prepare the uterus for birth. The change from the state of pregnancy to the state of parturition, which we call uterine transitioning, requires the actions of inflammatory mediators and results in an activated uterus capable of performing the physiology of labour. Interleukin (IL)-1β a...
Article
Full-text available
Purpose To determine the neuroprotective effect of estrogen on the structure and function of the retina exposed to an oxidative stress. Methods Male Sprague–Dawley rat pups were exposed to either hyperoxia (O2E: from P8 to P14) or bright light (LE: from P14 to P28) with or without 17 β-estradiol (βE2) treatment. Retinal structure (histology) and f...
Article
Birth is a complex biological event requiring genetic, cellular and physiological changes to the uterus, resulting in a uterus activated for completing the physiological processes of labor. We define the change from the state of pregnancy to the state of parturition as uterine transitioning, which requires the actions of inflammatory mediators and...
Article
Full-text available
Modulation of the cluster of differentiation-36 receptor (CD36) has proven promising for dampening pro-inflammatory macrophage signaling. For example, azapeptides (e.g., 1 and 2) bind CD36 selectively with high affinity, mitigate Toll-like receptor (TLR) agonist-induced overproduction of nitric oxide (NO), and reduce pro-inflammatory cytokine and c...
Article
High nuclear expression of G protein‐coupled receptors, including kinin B1 receptors (B1R), has been observed in several human cancers, but the clinical significance of this is unknown. We put forward the hypothesis that these “nuclearized” kinin B1R contribute to tumorigenicity and can be a new target in anticancer strategies. Our initial immunost...
Article
Full-text available
Antenatal inflammation as seen with chorioamnionitis is harmful to foetal/neonatal organ development including to eyes. Although the major pro-inflammatory cytokine IL-1β participates in retinopathy induced by hyperoxia (a predisposing factor to retinopathy of prematurity), the specific role of antenatal IL-1β associated with preterm birth (PTB) in...