A bibliometric analysis: Ca fluxes and inflammatory phenotyping by flow cytometry in peripheral blood mononuclear cells.

Background: The immune system, composed of organs, tissues, cells, and proteins, is the key to protecting the body from external biological attacks and inflammation. The latter occurs in several pathologies, such as cancers, type 1 diabetes, and human immunodeficiency virus infection. Immunophenotyping by flow cytometry is the method of choice for diagnosing these pathologies.

Aging is associated with impaired triggering of TRPV3-mediated cutaneous vasodilation: a crucial process for local heat exposure.

Sensing temperature is vitally important to adapt our body to environmental changes. Local warm detection is required to initiate regulation of cutaneous blood flow, which is part of the peripheral thermoregulatory mechanisms, and thus avoid damage to surrounding tissues. The mechanisms mediating cutaneous vasodilation during local heat stress are impaired with aging.

TRPV1 Channels Are New Players in the Reticulum-Mitochondria Ca Coupling in a Rat Cardiomyoblast Cell Line.

The Ca release in microdomains formed by intercompartmental contacts, such as mitochondria-associated endoplasmic reticulum membranes (MAMs), encodes a signal that contributes to Ca homeostasis and cell fate control. However, the composition and function of MAMs remain to be fully defined. Here, we focused on the transient receptor potential vanilloid 1 (TRPV1), a Ca-permeable ion channel and a polymodal nociceptor.

SERCA2 phosphorylation at serine 663 is a key regulator of Ca homeostasis in heart diseases.

Despite advances in cardioprotection, new therapeutic strategies capable of preventing ischemia-reperfusion injury of patients are still needed. Here, we discover that sarcoplasmic/endoplasmic reticulum Ca ATPase (SERCA2) phosphorylation at serine 663 is a clinical and pathophysiological event of cardiac function. Indeed, the phosphorylation level of SERCA2 at serine 663 is increased in ischemic hearts of patients and mouse.

Expression of the Calcium-Binding Protein CALB1 Is Induced and Controls Intracellular Ca Levels in Senescent Cells.

In response to many stresses, such as oncogene activation or DNA damage, cells can enter cellular senescence, a state of proliferation arrest accompanied by a senescence-associated secretory phenotype (SASP). Cellular senescence plays a key role in many physiopathological contexts, including cancer, aging and aging-associated diseases, therefore, it is critical to understand how senescence is regulated. Calcium ions (Ca) recently emerged as pivotal regulators of cellular senescence.

Impaired aerobic capacity and premature fatigue preceding muscle weakness in the skeletal muscle Tfam-knockout mouse model.

Mitochondrial diseases are genetic disorders that lead to impaired mitochondrial function, resulting in exercise intolerance and muscle weakness. In patients, muscle fatigue due to defects in mitochondrial oxidative capacities commonly precedes muscle weakness. In mice, deletion of the fast-twitch skeletal muscle-specific Tfam gene (Tfam KO) leads to a deficit in respiratory chain activity, severe muscle weakness and early death.

Reduced reticulum-mitochondria Ca transfer is an early and reversible trigger of mitochondrial dysfunctions in diabetic cardiomyopathy.

Type 2 diabetic cardiomyopathy features Ca signaling abnormalities, notably an altered mitochondrial Ca handling. We here aimed to study if it might be due to a dysregulation of either the whole Ca homeostasis, the reticulum-mitochondrial Ca coupling, and/or the mitochondrial Ca entry through the uniporter. Following a 16-week high-fat high-sucrose diet (HFHSD), mice developed cardiac insulin resistance, fibrosis, hypertrophy, lipid accumulation, and diastolic dysfunction when compared to standard diet.

The Contractile Phenotype of Skeletal Muscle in TRPV1 Knockout Mice is Gender-Specific and Exercise-Dependent.

The transient receptor potential vanilloid 1 (TRPV1) belongs to the transient receptor potential superfamily of sensory receptors. TRPV1 is a non-selective cation channel permeable to Ca that is capable of detecting noxious heat temperature and acidosis. In skeletal muscles, TRPV1 operates as a reticular Ca-leak channel and several mutations have been associated with two muscle disorders: malignant hyperthermia (MH) and exertional heat stroke (EHS).

Variations in the TRPV1 gene are associated to exertional heat stroke.

Objectives: Exertional Heat Stroke (EHS) is one of the top three causes of sudden death in athletes. Extrinsic and intrinsic risk factors have been identified but the genetic causes still remain unclear. Our aim was to identify genes responsible for EHS, which is a necessary step to identify patients at risk and prevent crises.

Acute Induction of Translocon-Mediated Ca Leak Protects Cardiomyocytes Against Ischemia/Reperfusion Injury.

During myocardial infarction, dysregulation of Ca homeostasis between the reticulum, mitochondria, and cytosol occurs in cardiomyocytes and leads to cell death. Ca leak channels are thought to be key regulators of the reticular Ca homeostasis and cell survival. The present study aimed to determine whether a particular reticular Ca leak channel, the translocon, also known as translocation channel, could be a relevant target against ischemia/reperfusion-mediated heart injury.

Differential Effect of Glucose on ER-Mitochondria Ca Exchange Participates in Insulin Secretion and Glucotoxicity-Mediated Dysfunction of β-Cells.

Glucotoxicity-induced β-cell dysfunction in type 2 diabetes is associated with alterations of mitochondria and the endoplasmic reticulum (ER). Both organelles interact at contact sites, defined as mitochondria-associated membranes (MAMs), which were recently implicated in the regulation of glucose homeostasis. The role of MAMs in β-cells is still largely unknown, and their implication in glucotoxicity-associated β-cell dysfunction remains to be defined.

Highly Variable Sialylation Status of Donor-Specific Antibodies Does Not Impact Humoral Rejection Outcomes.

Clinical outcome in antibody-mediated rejection (AMR) shows high inter-individual heterogeneity. Sialylation status of the Fc fragment of IgGs is variable, which could modulate their ability to bind to C1q and/or Fc receptors. In this translational study, we evaluated whether DSA sialylation influence AMR outcomes.

The Role of the Anti-Aging Protein Klotho in IGF-1 Signaling and Reticular Calcium Leak: Impact on the Chemosensitivity of Dedifferentiated Liposarcomas.

By inhibiting Insulin-Like Growth Factor-1-Receptor (IGF-1R) signaling, Klotho (KL) acts like an aging- and tumor-suppressor. We investigated whether impacts the aggressiveness of liposarcomas, in which IGF-1R signaling is frequently upregulated. Indeed, we observed that a higher expression in liposarcomas is associated with a better outcome for patients.

TRPV1 variants impair intracellular Ca signaling and may confer susceptibility to malignant hyperthermia.

Purpose: Malignant hyperthermia (MH) is a pharmacogenetic disorder arising from uncontrolled muscle calcium release due to an abnormality in the sarcoplasmic reticulum (SR) calcium-release mechanism triggered by halogenated inhalational anesthetics. However, the molecular mechanisms involved are still incomplete.

Methods: We aimed to identify transient receptor potential vanilloid 1 (TRPV1) variants within the entire coding sequence in patients who developed sensitivity to MH of unknown etiology.

HLA-DRB3/4/5 mismatches are associated with increased risk of acute GVHD in 10/10 matched unrelated donor hematopoietic cell transplantation.

Matching for HLA-A, -B, -C, and -DRB1 loci (8/8 match) is currently the gold standard for unrelated donor hematopoietic cell transplantation (HCT). In Europe, patients are also matched at the HLA-DQB1 loci (10/10 match). However, there is increasing evidence that matching at HLA-DRB3/4/5 loci may help to lower transplant-related morbidity and mortality.

Prevalence, Risk Factors, and Impact of Donor-Specific Alloantibodies After Adult Liver Transplantation.

The incidence and impact of anti-human leukocyte antigen donor-specific alloantibodies (DSAs) developing after liver transplantation (LT) remains controversial and not extensively studied. The aim of the present study was to assess the incidence of DSAs, to identify risk factors for the development of DSAs, and to understand the impact of DSAs in a large population of adult LT recipients. This single-center retrospective study included all adult patients who underwent a first LT between 2000 and 2010 in our center.

Deleterious impact of C3d-binding donor-specific anti-HLA antibodies after pediatric liver transplantation.

Background: The prevalence and clinical impact of anti-HLA donor-specific antibodies (DSA) after liver transplantation (LT) have not been extensively studied, especially in pediatric population.

Methods: The present cross-sectional study included 100 patients who underwent a first LT in childhood. Anti HLA immunization study was performed at a single time point during routine follow-up using Luminex® single antigen tests with classical anti-IgG conjugate and anti-C3d conjugate.

Computer-assisted topological analysis of renal allograft inflammation adds to risk evaluation at diagnosis of humoral rejection.

Antibody-mediated rejection is associated with heterogeneous kidney allograft outcomes. Accurate evaluation of risk for graft loss at time of diagnosis is necessary to offer personalized treatment. In contrast with serological and molecular assessment, morpho-histological evaluation of antibody-mediated rejection lesions has not significantly evolved.

Protection of Human Pancreatic Islets from Lipotoxicity by Modulation of the Translocon.

Type 2 diabetes is characterized by peripheral insulin resistance and pancreatic beta cell dysfunction. Elevated free fatty acids (FFAs) may impair beta cell function and mass (lipotoxicity). Altered calcium homeostasis may be involved in defective insulin release.

Exosome-like vesicles released from lipid-induced insulin-resistant muscles modulate gene expression and proliferation of beta recipient cells in mice.

Aims/hypothesis: The crosstalk between skeletal muscle (SkM) and beta cells plays a role in diabetes aetiology. In this study, we have investigated whether SkM-released exosome-like vesicles (ELVs) can be taken up by pancreatic beta cells and can deliver functional cargoes.

Methods: Mice were fed for 16 weeks with standard chow diet (SCD) or with standard diet enriched with 20% palmitate (HPD) and ELVs were purified from quadriceps muscle.