Autophagy and Protein Quality Control in Parkinson's Disease.

Autophagy is a vital cellular process responsible for the degradation of proteins, organelles, and other cellular components within lysosomes. In neurons, basal autophagy is indispensable for maintaining cellular homeostasis and protein quality control. Accordingly, lysosomal dysfunction has been proposed to be associated with neurodegeneration, and with Parkinson's disease (PD) in particular.

Understanding immune system dysfunction and its context in mood disorders: psychoneuroimmunoendocrinology and clinical interventions.

Mood disorders include a set of psychiatric manifestations of increasing prevalence in our society, being mainly represented by major depressive disorder (MDD) and bipolar disorder (BD). The etiopathogenesis of mood disorders is extremely complex, with a wide spectrum of biological, psychological, and sociocultural factors being responsible for their appearance and development. In this sense, immune system dysfunction represents a key mechanism in the onset and pathophysiology of mood disorders, worsening mainly the central nervous system (neuroinflammation) and the periphery of the body (systemic inflammation).

Family planning and contraception in people with multiple sclerosis: perspectives for obstetricians, gynaecologists, and other health care professionals involved in reproductive planning.

Purpose: Multiple sclerosis (MS) is often diagnosed in people of reproductive age. However, family planning counselling is not always integrated within MS care. Decisions on family planning can be further complicated by potential side effects associated with several disease-modifying therapies.

Regulation of Clusterin in the Heart and Plasma of Mice After Transverse Aortic Constriction.

Chronic pressure overload induces adverse cardiac remodelling characterised by left ventricular (LV) hypertrophy and fibrosis, leading to heart failure (HF). Identification of new biomarkers for adverse cardiac remodelling enables us to better understand this process and, consequently, to prevent HF. We recently identified clusterin (CLU) as a biomarker of cardiac remodelling and HF after myocardial infarction.

Long-term follow-up of hereditary hemorrhagic telangiectasia patients without significant pulmonary right-to-left shunt at screening.

Objectives: To describe the incidence of pulmonary arteriovenous malformations (PAVM)-related complications, right-to-left shunt (RLS) progression at transthoracic contrast echocardiography (TTCE) and development of treatable PAVM during long-term follow-up in hereditary hemorrhagic telangiectasia (HHT) patients with RLS grades 0-1 at screening TTCE.

Methods: Observational prospective study including adult HHT patients with grades 0-1 RLS at screening TTCE. Those requiring previous embolization of PAVM were excluded.

Molecular features of the serological IgG repertoire elicited by egg-based, cell-based, or recombinant haemagglutinin-based seasonal influenza vaccines: a comparative, prospective, observational cohort study.

Background: Egg-based inactivated quadrivalent seasonal influenza vaccine (eIIV4), cell culture-based inactivated quadrivalent seasonal influenza vaccine (ccIIV4), and recombinant haemagglutinin (HA)-based quadrivalent seasonal influenza vaccine (RIV4) have been licensed for use in the USA. In this study, we used antigen-specific serum proteomics analysis to assess how the molecular composition and qualities of the serological antibody repertoires differ after seasonal influenza immunisation by each of the three vaccines and how different vaccination platforms affect the HA binding affinity and breadth of the serum antibodies that comprise the polyclonal response.

Methods: In this comparative, prospective, observational cohort study, we included female US health-care personnel (mean age 47·6 years [SD 8]) who received a single dose of RIV4, eIIV4, or ccIIV4 during the 2018-19 influenza season at Baylor Scott & White Health (Temple, TX, USA).

Emerging role of circulating piRNAs in the diagnosis of heart transplant rejection.

Background: Liquid biopsy offers a potential alternative to decrease or eliminate endomyocardial biopsy for diagnosing allograft rejection. p-element-induced wimpy testis-interacting RNAs (piRNAs) are novel and promising disease biomarkers for their intrinsic characteristics such as stability in body fluids; however, their role in allograft rejection remains unexplored.

Methods: A training set based on small RNA sequencing technology was performed to identify piRNAs in endomyocardial tissue (n = 8) and serum samples (n = 40) from patients following heart transplantation.

Repurposed drugs as PCSK9-LDLR disruptors for lipid lowering and cardiovascular disease therapeutics.

The PCSK9 protein binds to LDL receptors (LDLR), leading to their degradation and reduced expression on cell surfaces. This decreased the clearance of LDL cholesterol from the bloodstream, thereby increasing the risk of coronary artery diseases. Targeting the PCSK9-LDL receptor interaction is crucial for regulating LDL cholesterol levels and preventing cardiovascular disease.

Relevance of recurrent venous thromboembolism according to location of metastasis in patients with cancer-associated thrombosis. A cohort study.

Background: Risk of VTE recurrence (VTEr) in patients with cancer-associated thrombosis (CAT) is high. Cancer-related risk factors for VTEr have been studied, but information about the importance of location of metastasis is scarce.

Objectives: 1) Evaluate rate of VTEr in CAT patients according to location of metastasis, and 2) Identify variables associated to VTEr during long-term follow-up.

Peripheral GABA receptors - Physiological relevance and therapeutic implications.

The role of γ- aminobutyric acid (GABA) and GABA receptors is not only essential for neurotransmission in the central nervous system (CNS), but they are also involved in communication in various peripheral tissues such as the pancreas, liver, kidney, gastrointestinal tract, trachea, immune cells and blood vessels. GABA receptors located outside the CNS ("peripheral GABA receptors") enable both neuronal and non-neuronal GABA-ergic signaling in various physiological processes and are generally thought to have similar properties to the extrasynaptic receptors in the CNS. By activating these peripheral receptors, GABA and various GABA receptor modulators, including drugs such as benzodiazepines and general anesthetics, may contribute to or otherwise affect the maintenance of general body homeostasis.

Impact of Coenzyme Q on Mitochondrial Metabolism: A Complementary Study Using Fluorescence Lifetime Imaging and Electron Microscopy.

Background: Coenzyme Q (CoQ), also known as ubiquinone-10, is an important molecule of the mitochondrial respiratory chain that acts as an electron carrier between complexes I, II, and III and additionally functions as an antioxidant. Due to its bioenergetic properties, CoQ is of high interest for therapeutic and cosmetic use. This study aims to characterize the metabolic impact of CoQ on primary human dermal fibroblasts (HDF) using fluorescence lifetime imaging microscopy (FLIM) and electron microscopy.

Decellularized Extracellular Matrix and Polyurethane Vascular Grafts Have Positive Effects on the Inflammatory and Pro-Thrombotic State of Aged Endothelial Cells.

In vitro assessment of small-diameter synthetic vascular grafts usually uses standard cell culture conditions with early-passage cells. However, these conduits are mainly implanted in elderly patients and are subject to complex cellular interactions influenced by age and inflammation. Understanding these factors is central to the development of vascular grafts tailored to the specific needs of patients.

Immunoinformatic approach to design T cell epitope-based chimeric vaccine targeting multiple serotypes of dengue virus.

The global dengue outbreak is a significant public health concern, with the World Health Organization recording over 3 million cases and a 0.04% case fatality rate until July 2023. The infection rate is anticipated to rise in vulnerable regions worldwide.

Novel Gene Biomarkers Specific to Human Mesenchymal Stem Cells Isolated from Bone Marrow.

In this paper, we present a comparative analysis of the transcriptomic profile of three different human cell types: hematopoietic stem cells (HSCs), bone marrow-derived mesenchymal stem cells (MSCs) and fibroblasts (FIBs). The work aims to identify unique genes that are differentially expressed as specific markers of bone marrow-derived MSCs, and to achieve this undertakes a detailed analysis of three independent datasets that include quantification of the global gene expression profiles of three primary cell types: HSCs, MSCs and FIBs. A robust bioinformatics method, called , is used to assess the specific association between one or more genes expressed in a sample and the outcome variable, that is, the 'cell type' provided as a single univariate response.

Should We Offer Universal Germline Genetic Testing to All Patients with Pancreatic Cancer? A Multicenter Study.

Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a significant percentage of germline pathogenic variants (GPVs). Unlike in the United States, routine universal genetic testing is not performed in Europe. The aim of the study is to evaluate the diagnostic yield of germline genetic testing in all patients with PDAC.