Effects of Heparan Sulfate Trisaccharide Containing Oleanolic Acid in Attenuating Hyperphosphorylated Tau-Induced Cell Dysfunction Associated with Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia, marked by progressive brain degeneration and cognitive decline. A major pathological feature of AD is the accumulation of hyperphosphorylated tau (p-tau) in the form of neurofibrillary tangles (NFTs), which leads to neuronal death and neurodegeneration. P-tau also induces endoplasmic reticulum (ER) stress and activates the unfolded protein response, causing inflammation and apoptosis.

Measuring the impact of hospitalisation for infectious diseases on the quality of life of older patients in four European countries: the AEQUI longitudinal matched cohort study (2020-2023).

Objectives: To evaluate the impact of hospitalisation for infectious diseases on the Health-Related Quality of life (HRQOL), multidimensional frailty, and functioning of older patients, we conducted a longitudinal matched cohort study in four European countries.

Methods: HRQOL, frailty, and functioning were assessed using validated questionnaires at inclusion, at discharge, and up to six months later (M6) in patients aged over 65 years hospitalised for severe acute respiratory or bloodstream infections, and matched controls hospitalised for non-infectious conditions. Comparative analyses employed multilevel mixed-effect linear or logistic models to assess changes from inclusion.

LCAT deficiency promotes hepatocellular carcinoma progression and lenvatinib resistance by promoting triglyceride catabolism and fatty acid oxidation.

Lecithin cholesterol acyltransferase (LCAT), a crucial enzyme in lipid metabolism, plays important yet poorly understood roles in tumours, especially in hepatocellular carcinoma (HCC). In this study, our investigation revealed that LCAT is a key downregulated metabolic gene and an independent risk factor for poor prognosis in patients with HCC. Functional experiments showed that LCAT inhibited HCC cell proliferation, migration and invasion.

The deubiquitinase USP5 prevents accumulation of protein aggregates in cardiomyocytes.

Protein homeostasis is crucial for maintaining cardiomyocyte (CM) function. Disruption of proteostasis results in accumulation of protein aggregates causing cardiac pathologies such as hypertrophy, dilated cardiomyopathy (DCM), and heart failure. Here, we identify ubiquitin-specific peptidase 5 (USP5) as a critical determinant of protein quality control (PQC) in CM.

Deficiency of orexin receptor type 1 in dopaminergic neurons increases novelty-induced locomotion and exploration.

Orexin signaling in the ventral tegmental area and substantia nigra promotes locomotion and reward processing, but it is not clear whether dopaminergic neurons directly mediate these effects. We show that dopaminergic neurons in these areas mainly express orexin receptor subtype 1 (Ox1R). In contrast, only a minor population in the medial ventral tegmental area express orexin receptor subtype 2 (Ox2R).

Smart Mesoporous Silica Nanoparticles in Cancer: Diagnosis, Treatment, Immunogenicity, and Clinical Translation.

In cancer research and personalized medicine, mesoporous silica nanoparticles (MSNs) have emerged as a significant breakthrough in both cancer treatment and diagnosis. MSNs offer targeted drug delivery, enhancing therapeutic effectiveness while minimizing adverse effects on healthy cells. Due to their unique characteristics, MSNs provide targeted drug delivery, maximizing therapeutic effectiveness with minimal adverse effects on healthy cells.

Sphingosine-1-Phosphate, a Marker of Endothelial Injury and Disease Severity in Preeclampsia.

Background: Preeclampsia is a hypertensive pregnancy disorder marked by endothelial damage. Healthy endothelium is covered by a protective glycocalyx layer, which, when degraded, releases detectable products into the blood. Sphingosine-1-phosphate (S1P) is a cardiovascular biomarker involved in glycocalyx preservation, linked to placentation and preeclampsia development.

Detection of clinically relevant variants in the gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL.

In chronic lymphocytic leukemia, the reliability of next-generation sequencing (NGS) to detect variants ≤10% allelic frequency (low-VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.

Single-cell transcriptomics reveals the heterogeneity and function of mast cells in human ccRCC.

Introduction: The role of mast cells (MCs) in clear cell renal carcinoma (ccRCC) is unclear, and comprehensive single-cell studies of ccRCC MCs have not yet been performed.

Methods: To investigate the heterogeneity and effects of MCs in ccRCC, we studied single-cell transcriptomes from four ccRCC patients, integrating both single-cell sequencing and bulk tissue sequencing data from online sequencing databases, followed by validation via spatial transcriptomics and multiplex immunohistochemistry (mIHC).

Results: We identified four MC signature genes (TPSB2, TPSAB1, CPA3, and HPGDS).

Meeting report - Alpine desmosome disease meeting 2024: advances and emerging topics in desmosomes and related diseases.

Desmosomes are adhesive cell contacts abundant in tissues exposed to mechanical strain, such as the stratified and simple epithelia of the epidermis and mucous membranes, as well as the myocardium. Besides their role in mechanical cell cohesion, desmosomes also modulate pathways important for tissue differentiation, wound healing and immune responses. Dysfunctional desmosomes, resulting from pathogenic variants in genes encoding desmosomal components, autoantibodies targeting desmosomal adhesion molecules or inflammation, cause the life-threatening diseases arrhythmogenic cardiomyopathy and pemphigus and contribute to the pathogenesis of inflammatory bowel diseases.

Multifactorial approach is needed to unravel the maturation phases of human neurons derived from induced pluripotent stem cells.

Neurons derived from induced pluripotent stem cells (h-iPSC-Ns) provide an invaluable model for studying the physiological aspects of human neuronal development under healthy and pathological conditions. However, multiple studies have demonstrated that h-iPSC-Ns exhibit a high degree of functional and epigenetic diversity. Due to the imprecise characterization and significant variation among the currently available maturation protocols, it is essential to establish a set of criteria to standardize models and accurately characterize and define the developmental properties of human neurons derived from iPSCs.

Predictive value of myositis antibodies: role of semiquantitative classification and positivity for more than one autoantibody.

Objectives: We assessed the positive predictive value (PPV) of 17 myositis antibodies for having a diagnosis of myositis and other myositis-spectrum conditions (interstitial lung disease (ILD), connective tissue diseases (CTD), malignancy) and evaluated the impact of semiquantitative classification and antibody overlap on the PPVs.

Materials And Methods: We retrospectively identified 1068 individuals ≥18 years who tested positive for ≥1 antibody in the EUROLINE myositis line blot assay or positive for anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) in an ELISA-based test between 2015 and 2020 in 15 out of the 20 hospital districts in Finland. We extracted clinical diagnoses from the Care Register for Health Care between January 2013 and June 2022.

Sex and age-related day-to-day variability in the skin microcirculation during post-occlusive reactive hyperemia.

Introduction: Little is known about the day-to-day variability of different skin microcirculation parameters, and how this variability is influenced by age and sex. The aim was to examine the day-to-day variability of microcirculatory parameters in relation to age and sex.

Methods: The cutaneous microcirculation was measured using a fiber optic probe integrating laser Doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) to measure oxygen saturation, red blood cell (RBC) tissue fraction, speed-resolved and conventional perfusion.

Mitochondrial regulation of obesity by POMC neurons.

Pro-opiomelanocortin (POMC) neurons, nestled in the hypothalamus, play a pivotal role in the intricate coordination of energy homeostasis and metabolic pathways. These neurons' mitochondria, often hailed as the cell's powerhouses, are crucial for maintaining cellular energy equilibrium and metabolic functionality. Recent research has illuminated the complex interplay between mitochondrial dynamics and POMC neuronal activity, underscoring their critical involvement in the pathogenesis of a spectrum of metabolic disorders, notably obesity and diabetes.

Characterizing the regulatory effects of H2A.Z and SWR1-C on gene expression during hydroxyurea exposure in Saccharomyces cerevisiae.

Chromatin structure and DNA accessibility are partly modulated by the incorporation of histone variants. H2A.Z, encoded by the non-essential HTZ1 gene in S.

The Calcium-Sensing Receptor in the Thick Ascending Limb and the Renal Response to Hypercalcemia.

Background: The parathyroid calcium-sensing receptor (CASR) controls the release of parathyroid hormone (PTH) in response to changes in serum calcium levels. Activation of the renal CASR increases urinary calcium excretion and is particularly important when CASR-dependent reductions in PTH fail to lower serum calcium. However, the role of the renal CASR in protecting against hypercalcemia and the direct effects of chronic CASR activation on tubular calcium handling remains to be fully elucidated.

Anterior segment optical coherence tomography (AS-OCT) assisted analysis of characteristics of graft dehiscence after Descemet membrane endothelial keratoplasty (DMEK) for failed penetrating keratoplasty.

Purpose: To analyse anterior segment optical coherence tomography (AS-OCT) parameters of graft dehiscence after Descemet membrane endothelial keratoplasty (DMEK) for graft failure post penetrating keratoplasty (PK).

Methods: Retrospective evaluation of AS-OCT images of 142 dehiscences post-DMEK in 75 eyes. Dehiscences' size, depth, location, correlation with graft-host interface (GHI) override and step at GHI were assessed.

Integrated Network Pharmacology, Machine Learning and Experimental Validation to Identify the Key Targets and Compounds of for the Treatment of Breast Cancer.

Background: TiaoShenGongJian (TSGJ) decoction, a traditional Chinese medicine for breast cancer, has unknown active compounds, targets, and mechanisms. This study identifies TSGJ's key targets and compounds for breast cancer treatment through network pharmacology, machine learning, and experimental validation.

Methods: Bioactive components and targets of TSGJ were identified from the TCMSP database, and breast cancer-related targets from GeneCards, PharmGkb, and RNA-seq datasets.

Current methods for detecting and assessing HIV-1 antibody resistance.

Antiretroviral therapy is the standard treatment for HIV, but it requires daily use and can cause side effects. Despite being available for decades, there are still 1.5 million new infections and 700,000 deaths each year, highlighting the need for better therapies.

Chitosan/γ-PGA nanoparticles and IFN-γ immunotherapy: A dual approach for triple-negative breast cancer treatment.

Interferon-γ (IFN-γ) is a key mediator in antitumor immunity and immunotherapy responses, yet its clinical applications remain restricted to chronic granulomatous disease and malignant osteopetrosis. IFN-γ effectiveness as a standalone treatment has shown limited success in clinical trials and its potential for synergistic effects when combined with immunotherapies is under clinical exploration. A particularly compelling combination is that of IFN-γ with Toll-like receptor (TLR) agonists that holds significant promise for cancer treatment.

Intracellular concentration of ADA2 is a marker for monocyte differentiation and activation.

Adenosine, a critical molecule regulating cellular function both inside and outside cells, is controlled by two human adenosine deaminases: ADA1 and ADA2. While ADA1 primarily resides in the cytoplasm, ADA2 can be transported to lysosomes within cells or secreted outside the cell. Patients with ADA2 deficiency (DADA2) often suffer from systemic vasculitis due to elevated levels of TNF-α in their blood.

Exploring perceived barriers and attitudes in young adults towards antidepressant pharmacotherapy, including the implementation of pharmacogenetic testing to optimize prescription practices.

Introduction: The field of pharmacogenetics (PGx) is experiencing significant growth, with increasing evidence to support its application in psychiatric care, suggesting its potential to personalize treatment plans, optimize medication efficacy, and reduce adverse drug reactions. However, the perceived utility and practicability of PGx for psychiatric treatment in youth remains underexplored. This study investigated perceived barriers and attitudes in Australian young adults towards the implementation of PGx testing to guide antidepressant treatment in primary care.

Deleterious coding variation associated with autism is consistent across populations, as exemplified by admixed Latin American populations.

The past decade has seen remarkable progress in identifying genes that, when impacted by deleterious coding variation, confer high risk for autism spectrum disorder (ASD), intellectual disability, and other developmental disorders. However, most underlying gene discovery efforts have focused on individuals of European ancestry, limiting insights into genetic risks across diverse populations. To help address this, the Genomics of Autism in Latin American Ancestries Consortium (GALA) was formed, presenting here the largest sequencing study of ASD in Latin American individuals (n>15,000).

Decoding Gene Networks Controlling Hypothalamic and Prethalamic Neuron Development.

Neuronal subtypes derived from the embryonic hypothalamus and prethalamus regulate many essential physiological processes, yet the gene regulatory networks controlling their development remain poorly understood. Using single-cell RNA- and ATAC-sequencing, we analyzed mouse hypothalamic and prethalamic development from embryonic day 11 to postnatal day 8, profiling 660,000 cells in total. This identified key transcriptional and chromatin dynamics driving regionalization, neurogenesis, and differentiation.