Cannabidiol ameliorates mitochondrial disease via PPARγ activation in preclinical models.

Mutations in mitochondrial energy-producing genes lead to a heterogeneous group of untreatable disorders known as primary mitochondrial diseases (MD). Leigh syndrome (LS) is the most common pediatric MD and is characterized by progressive neuromuscular affectation and premature death. Here, we show that daily cannabidiol (CBD) administration significantly extends lifespan and ameliorates pathology in two LS mouse models, and improves cellular function in fibroblasts from LS patients.

Precise Targeting of Autoantigen-Specific B Cells in Lupus Nephritis with Chimeric Autoantibody Receptor T Cells.

Despite conventional therapy, lupus nephritis (LN) remains a significant contributor to short- and long-term morbidity and mortality. B cell abnormalities and the production of autoantibodies against nuclear complexes like anti-dsDNA are recognised as key players in the pathogenesis of LN. To address the challenges of chronic immunosuppression associated with current therapies, we have engineered T cells to express chimeric autoantibody receptors (DNA-CAART) for the precise targeting of B cells expressing anti-dsDNA autoantibodies.

Assessment of social behavior and chemosensory cue detection in an animal model of neurodegeneration.

Numerous studies have shown that aging in humans leads to a decline in olfactory function, resulting in deficits in acuity, detection threshold, discrimination, and olfactory-associated memories. Furthermore, impaired olfaction has been identified as a potential indicator for the onset of age-related neurodegenerative diseases, including Alzheimer's disease (AD). Studies conducted on mouse models of AD have largely mirrored the findings in humans, thus providing a valuable system to investigate the cellular and circuit adaptations of the olfactory system during natural and pathological aging.

Small-Extracellular-Vesicle-Derived miRNA Profile Identifies miR-483-3p and miR-326 as Regulators in the Pathogenesis of Antiphospholipid Syndrome (APS).

Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disease associated with recurrent thrombosis and/or obstetric morbidity with persistent antiphospholipid antibodies (aPL). Although these antibodies drive endothelial injury and thrombophilia, the underlying molecular mechanism is still unclear. Small extracellular vesicles (sEVs) contain miRNAs, key players in intercellular communication.

Genotype and Phenotype Influence the Personal Response to Prostaglandin Analogues and Beta-Blockers in Spanish Glaucoma and Ocular Hypertension Patients.

Analysis of the genotype that predicts the phenotypic characteristics of a cohort of glaucoma and ocular hypertension patients, and the correlation with their personal pharmacological response to beta-blockers (BB) and prostaglandin analogues (PGA). Prospective study that included 139 eyes from 72 patients under BB and/or PGA treatment, and in some cases other types of ocular hypotensive treatments. Five single-nucleotide polymorphisms were genotyped by real-time PCR assays: prostaglandin-F2α receptor (rs3766355, rs3753380); cytochrome-P450 2D6 (rs16947, rs769258); and beta-2-adrenergic receptor (rs1042714).

AMPA Receptor Function in Hypothalamic Synapses.

AMPA receptors (AMPARs) are critical for mediating glutamatergic synaptic transmission and plasticity, thus playing a major role in the molecular machinery underlying cellular substrates of memory and learning. Their expression pattern, transport and regulatory mechanisms have been extensively studied in the hippocampus, but their functional properties in other brain regions remain poorly understood. Interestingly, electrophysiological and molecular evidence has confirmed a prominent role of AMPARs in the regulation of hypothalamic function.

A retention-release mechanism based on RAB11FIP2 for AMPA receptor synaptic delivery during long-term potentiation.

It is well--established that Rab11-dependent recycling endosomes drive the activity-dependent delivery of AMPA receptors (AMPARs) into synapses during long-term potentiation (LTP). Nevertheless, the molecular basis for this specialized function of recycling endosomes is still unknown. Here, we have investigated RAB11FIP2 (FIP2 hereafter) as a potential effector of Rab11-dependent trafficking during LTP in rat hippocampal slices.

Interferon gamma, an important marker of response to immune checkpoint blockade in non-small cell lung cancer and melanoma patients.

Background: Programmed death-ligand 1 (PD-L1) may be induced by oncogenic signals or can be upregulated interferon gamma (IFN-γ). We have explored whether the expression of IFNG, the gene encoding IFN-γ, is associated with clinical response to the immune checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma patients. The role of inflammation-associated transcription factors STAT3, IKBKE, STAT1 and other associated genes has also been examined.

[Factors determining irregular attendance to follow-up visits among human immunodeficiency virus patients: results of the hospital survey of patients infected with human immunodeficiency virus].

Introduction: To describe the occurrence of non-regular attendance to follow-up visits among HIV patients and to analyze the determining factors.

Methods: One-day survey carried out annually (2002-2012) in public hospitals. Epidemiological, clinical and behavioral data are collected in all HIV-infected inpatients and outpatients receiving HIV-related care on the day of the survey.

The balance between receptor recycling and trafficking toward lysosomes determines synaptic strength during long-term depression.

The strength of excitatory synaptic transmission depends partly on the number of AMPA receptors (AMPARs) at the postsynaptic surface and, thus, can be modulated by membrane trafficking events. These processes are critical for some forms of synaptic plasticity, such as long-term potentiation and long-term depression (LTD). In the case of LTD, AMPARs are internalized and dephosphorylated in response to NMDA receptor activation.

PIP3 controls synaptic function by maintaining AMPA receptor clustering at the postsynaptic membrane.

Despite their low abundance, phosphoinositides are critical regulators of intracellular signaling and membrane compartmentalization. However, little is known of phosphoinositide function at the postsynaptic membrane. Here we show that continuous synthesis and availability of phosphatidylinositol-(3,4,5)-trisphosphate (PIP(3)) at the postsynaptic terminal is necessary for sustaining synaptic function in rat hippocampal neurons.

The tumour suppressor p53 regulates the expression of amyloid precursor protein (APP).

The expression of the APP (amyloid precursor protein), which plays a key role in the development of AD (Alzheimer's disease), is regulated by a variety of cellular mediators in a cell-dependent manner. In this study, we present evidence that p53 regulates the expression of the APP gene in neuroblastoma cells. Transient expression of ectopic p53, activation of endogenous p53 by the DNA-damaging drug camptothecin or Mdm2 (murine double minute 2) depletion decreases the intracellular levels of APP in murine N2abeta neuroblastoma cells.