Cancer Stem Cells from Definition to Detection and Targeted Drugs.

Cancers remain the second leading cause of mortality in the world. Preclinical and clinical studies point an important role of cancer/leukaemia stem cells (CSCs/LSCs) in the colonisation at secondary organ sites upon metastatic spreading, although the precise mechanisms for specific actions are still not fully understood. Reviewing the present knowledge on the crucial role of CSCs/LSCs, their plasticity, and population heterogeneity in treatment failures in cancer patients is timely.

Cardiolipin Membranes Promote Cytochrome Transformation of Polycyclic Aromatic Hydrocarbons and Their In Vivo Metabolites.

The catalytic properties of cytochrome (C) have captured great interest in respect to mitochondrial physiology and apoptosis, and hold potential for novel enzymatic bioremediation systems. Nevertheless, its contribution to the metabolism of environmental toxicants remains unstudied. Human exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with impactful diseases, and animal models have unveiled concerning signs of PAHs' toxicity to mitochondria.

Are There Lipid Membrane-Domain Subtypes in Neurons with Different Roles in Calcium Signaling?

Lipid membrane nanodomains or lipid rafts are 10-200 nm diameter size cholesterol- and sphingolipid-enriched domains of the plasma membrane, gathering many proteins with different roles. Isolation and characterization of plasma membrane proteins by differential centrifugation and proteomic studies have revealed a remarkable diversity of proteins in these domains. The limited size of the lipid membrane nanodomain challenges the simple possibility that all of them can coexist within the same lipid membrane domain.

Rafting on the Evidence for Lipid Raft-like Domains as Hubs Triggering Environmental Toxicants' Cellular Effects.

The plasma membrane lipid rafts are cholesterol- and sphingolipid-enriched domains that allow regularly distributed, sub-micro-sized structures englobing proteins to compartmentalize cellular processes. These membrane domains can be highly heterogeneous and dynamic, functioning as signal transduction platforms that amplify the local concentrations and signaling of individual components. Moreover, they participate in cell signaling routes that are known to be important targets of environmental toxicants affecting cell redox status and calcium homeostasis, immune regulation, and hormonal functions.

A Community-Based Participatory Framework to Co-Develop Patient Education Materials (PEMs) for Rare Diseases: A Model Transferable across Diseases.

At least 50% of chronic disease patients don't follow their care plans, leading to lower health outcomes and higher medical costs. Providing Patient Education Materials (PEMs) to individuals living with a disease can help to overcome these problems. PEMs are especially beneficial for people suffering from multisystemic and underrecognized diseases, such as rare diseases.

Stakeholders' views on drug development: the congenital disorders of glycosylation community perspective.

Background: Congenital disorders of glycosylation (CDG) are a large family of rare genetic diseases for which therapies are virtually nonexistent. However, CDG therapeutic research has been expanding, thanks to the continuous efforts of the CDG medical/scientific and patient communities. Hence, CDG drug development is a popular research topic.

Comparison of Laccases and Hemeproteins Systems in Bioremediation of Organic Pollutants.

Aim: Laccases and peroxidases have attracted great interest for industrial and environmental applications. These enzymes have a broad substrate range and a robust oxidizing ability. Moreover, using mediators or co-oxidants makes it possible to increase their catalytic activity and extend their substrate scope to more resistant chemical structures.

A Community-Led Approach as a Guide to Overcome Challenges for Therapy Research in Congenital Disorders of Glycosylation.

Congenital Disorders of Glycosylation (CDG) are a large family of rare genetic diseases for which effective therapies are almost nonexistent. To better understand the reasons behind this, to analyze ongoing therapy research and development (R&D) for CDG, and to provide future guidance, a community-led mixed methods approach was organized during the 4th World Conference on CDG for Families and Professionals. In the quantitative phase, electronic surveys pointed to the prioritization of six therapeutic R&D tools, namely biobanks, registries, biomarkers, disease models, natural history studies, and clinical trials.

Registered human trials addressing environmental and occupational toxicant exposures: Scoping review of immunological markers and protective strategies.

Exposure to pollution is a worldwide societal challenge participating in the etiology and progression of different diseases. However, the scarce information hinders our understanding of the actual level of human exposure and its specific effects. Inadequate and excessive immune responses underlie diverse chronic diseases.

Diabetes and Cannabinoid CB1 receptor deficiency promote similar early onset aging-like changes in the skin.

Background: The cannabinoid receptor type-1 (CBR) is a major regulator of metabolism, growth and inflammation. Yet, its potential role in the skin is not well understood. Our aim was to evaluate the role of CBR in aging-like diabetic skin changes by using a CBR knockout mouse model.

Reassessment of the experimental skin permeability coefficients of polycyclic aromatic hydrocarbons and organophosphorus pesticides.

Human exposure to polycyclic aromatic hydrocarbons (PAHs) and organophosphorus pesticides (OPPs) by dermal route is a continuing concern in environmental and occupational toxicology. Diverse authors have measured in vitro the absorption flux and permeability coefficient (k) of those compounds delivered on skin surface using volatile solvents. However, there isn't a harmonized method to obtain k when the test substance is deposited on the skin as a solid.

International consensus guidelines for phosphoglucomutase 1 deficiency (PGM1-CDG): Diagnosis, follow-up, and management.

Phosphoglucomutase 1 (PGM1) deficiency is a rare genetic disorder that affects glycogen metabolism, glycolysis, and protein glycosylation. Previously known as GSD XIV, it was recently reclassified as a congenital disorder of glycosylation, PGM1-CDG. PGM1-CDG usually manifests as a multisystem disease.

New Insights into Immunological Involvement in Congenital Disorders of Glycosylation (CDG) from a People-Centric Approach.

Congenital disorders of glycosylation (CDG) are rare diseases with variable phenotypes and severity. Immunological involvement remains a largely uncharted topic in CDG, mainly due to lack of robust data. To better characterize immune-related manifestations' prevalence, relevance, and quality-of-life (QoL) impact, we developed electronic questionnaires targeting (1) CDG patients and (2) the general "healthy" population.

Identification of new targets of S-nitrosylation in neural stem cells by thiol redox proteomics.

Nitric oxide (NO) is well established as a regulator of neurogenesis. NO increases the proliferation of neural stem cells (NSC), and is essential for hippocampal injury-induced neurogenesis following an excitotoxic lesion. One of the mechanisms underlying non-classical NO cell signaling is protein S-nitrosylation.

Molecular mechanisms linking environmental toxicants to cancer development: Significance for protective interventions with polyphenols.

Human exposure to environmental toxicants with diverse mechanisms of action is a growing concern. In addition to well-recognized carcinogens, various chemicals in environmental and occupational settings have been suggested to impact health, increasing susceptibility to cancer by inducing genetic and epigenetic changes. Accordingly, in this review, we have discussed recent insights into the pathological mechanisms of these chemicals, namely their effects on cell redox and calcium homeostasis, mitochondria and inflammatory signaling, with a focus on the possible implications for multi-stage carcinogenesis and its reversal by polyphenols.

Keeping an eye on congenital disorders of O-glycosylation: A systematic literature review.

Congenital disorders of glycosylation (CDG) are a rapidly growing family comprising >100 genetic diseases. Some 25 CDG are pure O-glycosylation defects. Even among this CDG subgroup, phenotypic diversity is broad, ranging from mild to severe poly-organ/system dysfunction.

Patient and observer reported outcome measures to evaluate health-related quality of life in inherited metabolic diseases: a scoping review.

Background: Health-related Quality of Life (HrQoL) is a multidimensional measure, which has gained clinical and social relevance. Implementation of a patient-centred approach to both clinical research and care settings, has increased the recognition of patient and/or observer reported outcome measures (PROMs or ObsROMs) as informative and reliable tools for HrQoL assessment. Inherited Metabolic Diseases (IMDs) are a group of heterogeneous conditions with phenotypes ranging from mild to severe and mostly lacking effective therapies.

Methyl-β-Cyclodextrin Impairs the Phosphorylation of the β₂ Subunit of L-Type Calcium Channels and Cytosolic Calcium Homeostasis in Mature Cerebellar Granule Neurons.

The activation of L-type calcium channels (LTCCs) prevents cerebellar granule neurons (CGNs) from entering low-K⁺-induced apoptosis. In previous works, we showed that LTCCs are largely associated with caveolin-1-rich lipid rafts in the CGN plasma membrane. In this work, we show that protein kinase A (PKA) and calmodulin-dependent protein kinase II (CaMK-II) are associated with caveolin-1-rich lipid rafts of mature CGNs, and we further show that treatment with the cholesterol-trapping and lipid raft-disrupting agent methyl-β-cyclodextrin decreases the phosphorylation level of the LTCC β₂ subunit and the steady-state calcium concentration in neuronal somas ([Ca]) to values close to those measured in 5 mM KCl proapoptotic conditions.

CDG Therapies: From Bench to Bedside.

Congenital disorders of glycosylation (CDG) are a group of genetic disorders that affect protein and lipid glycosylation and glycosylphosphatidylinositol synthesis. More than 100 different disorders have been reported and the number is rapidly increasing. Since glycosylation is an essential post-translational process, patients present a large range of symptoms and variable phenotypes, from very mild to extremely severe.

Recognizable phenotypes in CDG.

Pattern recognition, using a group of characteristic, or discriminating features, is a powerful tool in metabolic diagnostic. A classic example of this approach is used in biochemical analysis of urine organic acid analysis, where the reporting depends more on the correlation of pertinent positive and negative findings, rather than on the absolute values of specific markers. Similar uses of pattern recognition in the field of biochemical genetics include the interpretation of data obtained by metabolomics, like glycomics, where a recognizable pattern or the presence of a specific glycan sub-fraction can lead to the direct diagnosis of certain types of congenital disorders of glycosylation.

Stimulation and clustering of cytochrome b5 reductase in caveolin-rich lipid microdomains is an early event in oxidative stress-mediated apoptosis of cerebellar granule neurons.

The apoptosis of cerebellar granule neurons (CGN) induced by low potassium in the extracellular medium is a model of neuronal apoptosis where an overshot of reactive oxygen species (ROS) triggers the neuronal death. In this work, using dihydroethidium and L-012 as specific dyes for superoxide anion detection we show that this ROS overshot can be accounted by an increased release of superoxide anion to the extracellular medium. The amplitude and time course of the increase of superoxide anion observed early during apoptosis correlated with the increase of the content of soluble cytochrome b(5), a substrate of the NADH-dependent oxidase activity of the cytochrome b(5) reductase associated with lipid rafts in CGN.

Early disruption of the actin cytoskeleton in cultured cerebellar granule neurons exposed to 3-morpholinosydnonimine-oxidative stress is linked to alterations of the cytosolic calcium concentration.

Cytoskeleton damage is a frequent feature in neuronal cell death and one of the early events in oxidant-induced cell injury. This work addresses whether actin cytoskeleton reorganization is an early event of SIN-1-induced extracellular nitrosative/oxidative stress in cultured cerebellar granule neurons (CGN). The actin polymerization state, i.

L-type calcium channels and cytochrome b5 reductase are components of protein complexes tightly associated with lipid rafts microdomains of the neuronal plasma membrane.

The presence of cytosolic calcium microcompartments in neurons is well established. L-type voltage calcium channels play a leading role in the rise of cytosolic calcium in the neuronal soma and are sensitive to redox modulation. In a recent work [Samhan-Arias, A.