Search results for "LOM"

“Pro-youthful” factors in the “labyrinth” of cardiac rejuvenation

2016

IF 3.350; International audience; The mechanisms of aging and senescence include various endogenous and exogenous factors. Among cardiovascular diseases, heart failure is a typical age-related disease. New strategies to restore cardiomyocyte cells have been reported: endogenous substances that can regenerate the heart's cardiomyocytes have been described: follistatin like 1 (FSTL1), growth-differentiation factor 11 (GDF11) and insulin-like growth factor 1 (IGF-I). Manipulation of the different anti and pro-pathways is essential to discover new approaches to regenerative therapies. (C) 2016 Elsevier Inc. All rights reserved.

Acute telomerase components depletion triggers oxidative stress as an early event previous to telomeric shortening

2018

Loss of function of dyskerin (DKC1), NOP10 and TIN2 are responsible for different inheritance patterns of Dyskeratosis congenita (DC; ORPHA1775). They are key components of telomerase (DKC1 and NOP10) and shelterin (TIN2), and play an important role in telomere homeostasis. They participate in several fundamental cellular processes by contributing to Dyskeratosis congenita through mechanisms that are not fully understood. Presence of oxidative stress was postulated to result from telomerase ablation. However, the resulting disturbed redox status can promote telomere attrition by generating a vicious circle, which promotes cellular senescence. This fact prompted us to study if acute loss of …

Interactive effects of aging and aerobic capacity on energy metabolism-related metabolites of serum, skeletal muscle, and white adipose tissue

2021

ABSTRACTAerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, aging and their interaction on metabolism, we utilized rat models of low and high intrinsic aerobic capacity (LCRs/HCRs) and assessed the metabolomics of serum, muscle, and white adipose tissue (WAT). We compared LCRs and HCRs at two time points: Young rats were sacrificed at 9 months, and old rats were sacrificed at 21 months. Targeted and semi-quantitative metabolomics analysis was performed on ultra-pressure Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS)…

A novel microglial subset plays a key role in myelinogenesis in developing brain.

2017

Microglia are resident macrophages of the central nervous system that contribute to homeostasis and neuroinflammation. Although known to play an important role in brain development, their exact function has not been fully described. Here, we show that in contrast to healthy adult and inflammation-activated cells, neonatal microglia show a unique myelinogenic and neurogenic phenotype. A CD11c(+) microglial subset that predominates in primary myelinating areas of the developing brain expresses genes for neuronal and glial survival, migration, and differentiation. These cells are the major source of insulin-like growth factor 1, and its selective depletion from CD11c(+) microglia leads to impa…

Does telomere length predict decline in physical functioning in older twin sisters during an 11-year follow-up?

2016

Background: Leucocyte telomere length (LTL) is known to be associated with mortality, but its association with age-related decline in physical functioning and the development of disability is less clear. This study examined the associations between LTL and physical functioning, and investigated whether LTL predicts level of physical functioning over an 11- year follow-up. Methods: Older mono- (MZ) and dizygotic (DZ) twin sisters (n=386) participated in the study. Relative LTL was measured by qPCR at baseline. Physical functioning was measured by 6-min walking distance and level of physical activity (PA). Walking distance was measured at baseline and at 3-year follow-up. PA was assessed by q…

Chemoprevention and therapeutic role of essential oils and phenolic compounds: Modeling tumor microenvironment in glioblastoma

2021

Glioblastoma (GBM) is the most common primary tumor of the central nervous system. Current treatments available for GBM entails surgical resection followed by temozolomide chemotherapy and/or radiotherapy, which are associated with multidrug resistance and severe side effects. While this treatment could yield good results, in almost all cases, patients suffer from relapse, which leads to reduced survival rates. Thus, therapeutic approaches with improved efficiency and reduced off-target risks are needed to overcome these problems. Regarding this, natural products appear as a safe and attractive strategy as chemotherapeutic agents or adjuvants in the treatment of GBM. Besides the increasing …

Physicochemical and Preclinical Evaluation of Spermine-Derived Surfactant Liposomes for in Vitro and in Vivo siRNA-Delivery to Liver Macrophages

2016

Herein we report on a liposomal system for siRNA delivery consisting of cholesterol (Chol), distearoylphosphatidylcholine (DSPC), and surfactant TF (1-hydroxy-50-amino-3,4,7,10,13,16,19,22-octaoxa-37,41,45-triaza-pentacontane), a novel spermine derivative (HO-EG8-C12-spermine) which has shown improved siRNA delivery to cells in vitro and in vivo. Predominantly single-walled liposomes with reproducible sizes and moderately broad size distributions were generated with an automated extrusion device. The liposomes remained stable when prepared in the presence of siRNA at N/P ratios of 17-34. However, when mixed with human serum in equal volumes, larger aggregates in the size range of several hu…

Incidentalome in Neurogenetics: Pathogenic Variant of NSD1 in a Patient With Spinocerebellar Ataxia (SCA)

2018

Background: Genetic studies of late-onset sporadic ataxias (>40 years of age) are not routinely indicated. For unresolved cases, next-generation sequencing (NGS) tools, such as whole-exome sequencing (WES), are available for a definitive diagnosis.Case presentation: Our patient is a woman with a usual facial phenotype and anthropometry, who developed ataxia at 45 years of age, with no relevant family history and an initial clinical approach that ruled out common aetiologies. WES was performed when the patient was 54 years old. The results identified the heterozygous pathogenic variant c.248delA (p.N83MfsX4) in the nuclear receptor-binding SET domain protein 1 (NSD1; MIM 606681) gene (rel…

2019

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) leading to CNS inflammation and neurodegeneration. Current anti-inflammatory drugs have only limited efficacy on progressive neurodegenerative processes underlining the need to understand immune-mediated neuronal injury. Cell adhesion molecules play an important role for immune cell migration over the blood-brain barrier whereas their role in mediating potentially harmful contacts between invading immune cells and neurons is incompletely understood. Here, we assess the role of the CNS-specific neuronal adhesion molecule ICAM-5 using experimental autoimmune encephalomyelitis (EAE), an animal model of …

Dextran-based therapeutic nanoparticles for hepatic drug delivery.

2016

Aim: Evaluation of dextran-based nanoparticles (DNP) as a drug delivery system to target myeloid cells of the liver. Materials & methods: DNP were synthesized and optionally PEGylated. Their toxicity and cellular uptake were studied in vitro. Empty and siRNA-carrying DNP were tested in vivo with regard to biodistribution and cellular uptake. Results: In vitro, DNP were taken up by cells of the myeloid lineage without compromising their viability. In vivo, empty and siRNA-carrying DNP distributed to the liver where a single treatment addressed approximately 70% of macrophages and dendritic cells. Serum parameters indicated no in vivo toxicity. Conclusion: DNP are multifunctional liver-s…