A scoping review evaluating the current state of gut microbiota and its metabolites in valvular heart disease physiopathology.

Background: The human microbiome is crucial in regulating intestinal and systemic functions. While its role in cardiovascular disease is better understood, the link between intestinal microbiota and valvular heart diseases (VHD) remains largely unexplored.

Methods: Peer-reviewed studies on human, animal or cell models analysing gut microbiota profiles published up to April 2024 were included.

Gut metabolomic and microbiota analyses in ALS mice reveal specific metabolites despite the absence of significant gut dysbiosis.

Objective: Over the past years, interest in the role of gut microbiota in neurodegenerative diseases has emerged. Despite numerous publications over the past decade, both in human and pre-clinical studies, there is no clear consensus on the microbiota's role or involvement in ALS. Few studies on mouse models of ALS highlighted a correlation between specific bacteria species and the prognostic or severity of the disease.

Dynamic Expression of Genes Encoding Ubiquitin Conjugating Enzymes (E2s) During Neuronal Differentiation and Maturation: Implications for Neurodevelopmental Disorders and Neurodegenerative Diseases.

The ubiquitination process plays a crucial role in neuronal differentiation and function. Numerous studies have focused on the expression and functions of E3 ligases during these different stages, far fewer on E2 conjugating enzymes. In mice, as in humans, these E2s belong to 17 conjugating enzyme families.

Glycolytic activity following anti-CD19 CAR-T cell infusion in non-Hodgkin lymphoma.

Energy metabolism of chimeric antigen receptor-T cells (CAR-T) activation in humans remains unexplored. As a glycolytic activity surrogate, we investigated the dynamics of peripheral blood (PB) lactate in the first weeks post-CAR-T infusion. In 17 patients treated with CD28 harbording anti-CD19 CAR-T for relapsed/refractory non-Hodgkin lymphomas, PB lactate levels increased following CAR-T infusion.

Metabolomics of basal tears in amyotrophic lateral sclerosis: A cross-sectional study.

Purpose: Amyotrophic lateral sclerosis (ALS) clinical variability, along with the lack of conclusive diagnostic instruments, result in average diagnosis delays of 9 months. This study aimed to assess whether metabolomic profiling of basal tears in ALS patients could act as a biological marker for diagnosing ALS, predicting prognosis, and discriminating between endophenotypes.

Methods: A single-center prospective case-control study was conducted in France from September 2021 to March 2023 including patients with ALS according to the revised EI Escorial criteria.

N-Terminal Fragments of TDP-43-In Vitro Analysis and Implication in the Pathophysiology of Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration.

Abnormal cytoplasmic aggregates containing the TDP-43 protein and its fragments are present in the central nervous system of the majority of patients with amyotrophic lateral sclerosis (ALS) and in patients with frontotemporal lobar degeneration (FTLD). Many studies have focused on the C-terminal cleavage products of TDP-43 (CTFs), but few have focused on the N-terminal products (NTFs), yet several works and their protein domain composition support the involvement of NTFs in pathophysiology. In the present study, we expressed six NTFs of TDP-43, normally generated in vivo by proteases or following the presence of pathogenic genetic truncating variants, in HEK-293T cells.

Exploring amyotrophic lateral sclerosis through the visual system: A systematic review.

Background And Purpose: The human visual system relies on neural networks throughout the brain that are easily accessible for tests exploring eye structures and movements. Over the past two decades, investigations have been carried out on both afferent and efferent components of the visual system in people with amyotrophic lateral sclerosis (ALS). This approach might represent an innovative biomarker research strategy to better characterise the phenotypic variability of ALS.

A specific diagnostic metabolome signature in adult IgA vasculitis.

Introduction: IgA vasculitis diagnosis relies primarily on clinical features and is confirmed by pathological findings. To date, there is no reliable noninvasive diagnostic biomarker.

Objective: We aimed to explore the baseline serum metabolome of adult patients with IgA vasculitis to identify potential diagnostic biomarkers.

Pharmacometabolomics applied to low-dose interleukin-2 treatment in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease. The immunosuppressive functions of regulatory T lymphocytes (Tregs) are impaired in ALS, and correlate to disease progression. The phase 2a IMODALS trial reported an increase in Treg number in ALS patients following the administration of low-dose (ld) interleukin-2 (IL-2).

Corneal nerves and amyotrophic lateral sclerosis: an in vivo corneal confocal imaging study.

Objectives: Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disorder. Diagnosis is challenging due to its clinical heterogeneity and the absence of definitive diagnostic tools, leading to delays averaging between 9.1 and 27 months.

The effect of pH alterations on TDP-43 in a cellular model of amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons. The pathophysiology of ALS is not well understood but TDP-43 proteinopathy (aggregation and mislocalization) is one of the major phenomena described. Several factors can influence TDP-43 behavior such as mild pH alterations that can induce conformational changes in recombinant TDP-43, increasing its propensity to aggregate.

Sweet ending: When genetics prevent a dramatic CDG diagnostic mistake.

Herein, we described the case of a newborn male, from consanguineous parents, who developed, at day 11 of life, an obstructive hydrocephalus resulting from bilateral cerebellar hemorrhage without evident cause. Then, at 1 month, he developed a fulminant hepatitis with hyperammonia, hyperlactatemia and metabolic acidosis. Infectious and first line metabolic explorations were normal.

Neutrophil to Lymphocyte Ratio as a Prognostic Marker in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative motor neuron disease and remains misunderstood with a difficult diagnosis and prognosis. The implication of the immune system is recognized in ALS pathophysiology, hence the interest in leucocyte count as lymphocytes and neutrophils. The neutrophil-to-lymphocyte ratio (NLR) has recently been used as a prognosis factor to assess the progression of ALS.

No evidence for systemic low-grade inflammation in adult patients with early-treated phenylketonuria: The INGRAPH study.

The question of an increased cardiovascular risk has been recently raised in adults with phenylketonuria (PKU). As low-grade systemic inflammation increases cardiovascular risk, the INGRAPH study aimed to evaluate low-grade inflammation in adult PKU patients compared to healthy controls and to determine the potential influence of Phe-controlled diet on inflammation. Twenty early-treated adult PKU patients, including a subgroup of 15 classical PKU patients, and 20 healthy volunteers were included.

Increased acylcarnitines in infant heart failure indicate fatty acid oxidation inhibition: towards therapeutic options?

Aims: Heart failure in adults is characterized by reduction of long-chain fatty acid oxidation in favour of carbohydrate metabolism. This adaptive phenomenon becomes maladaptive because energy conversion decreases and lipid toxic derivatives known to impair cardiac function are accumulating. No data are available concerning metabolic modification in heart failure in children.

Joint manifestations revealing inborn metabolic diseases in adults: a narrative review.

Inborn metabolic diseases (IMD) are rare conditions that can be diagnosed during adulthood. Patients with IMD may have joint symptoms and the challenge is to establish an early diagnosis in order to institute appropriate treatment and prevent irreversible damage. This review describes the joint manifestations of IMD that may be encountered in adults.

Implication of Central Nervous System Barrier Impairment in Amyotrophic Lateral Sclerosis: Gender-Related Difference in Patients.

Central nervous system (CNS) barrier impairment has been reported in amyotrophic lateral sclerosis (ALS), highlighting its potential significance in the disease. In this context, we aim to shed light on its involvement in the disease, by determining albumin quotient (QAlb) at the time of diagnosis of ALS in a large cohort of patients. Patients from the university hospital of Tours ( = 307) were included in this monocentric, retrospective study.

Evaluation of arterial blood gas parameters as prognostic markers in amyotrophic lateral sclerosis.

Background: Forced vital capacity (FVC) remains difficult to determine for some patients suffering from amyotrophic lateral sclerosis (ALS) due to the rapid progression of the disease. Arterial blood gas (ABG) parameters could represent a valuable alternative. The aim of this study was therefore to evaluate the correlation between ABG parameters and FVC, along with the prognostic ability of ABG parameters, in a large cohort of ALS patients.

Clinical and biochemical footprints of inherited metabolic diseases. IX. Metabolic ear disease.

Damages to the ear are very diverse and can depend on the type of inherited metabolic diseases (IMD). Indeed, IMDs can affect all parts of the auditory system, from the outer ear to the central auditory process. We have identified 219 IMDs associated with various types of ear involvement which we classified into five groups according to the lesion site of the auditory system: congenital external ear abnormalities, acquired external ear abnormalities, middle ear involvement, inner ear or retrocochlear involvement, and unspecified hearing loss.

Comparison between PFN1 and SOD1 mutations in amyotrophic lateral sclerosis.

Background: The objective of this study was to characterize the prototypical phenotype of patients with amyotrophic lateral sclerosis (ALS) associated with PFN1 mutations in profilin 1 (PFN1) and to determine clinical indications to test for mutations in this gene.

Material And Methods: The phenotype of three relatives carrying the M114V PFN1 mutation are detailed here and are compared with those of patients with ALS linked to PFN1 previously reported in the literature.

Results: In this pedigree and in the literature, the main clinical findings which best describe familial ALS linked to PFN1 might be the following characteristics: pedigrees over five cases, age of onset around 50 years, site of onset systematically lower limbs and the absence of cognitive impairment.

Validation of metabolomic and lipidomic analyses of human tears using ultra-high-performance liquid chromatography tandem mass spectrometry.

To facilitate application in ophthalmological and systemic diseases, there is a need to standardize preanalytical and analytical steps for metabo-lipidomics in human tears. We assessed different methods for each step of the workflow, from sampling to omics profiles acquisition, to provide the largest metabo-lipidomic coverage with the most robust analytical criteria in human tears. We compared reproducibility according to different extraction methods, two sampling techniques, three volumes (2 μL, 5 μL, 10 μL) and eye laterality using ultra-high-performance liquid chromatography coupled with tandem high-resolution mass spectrometry for metabolomic and lipidomic application.