LBD

BACKGROUND: Alzheimer's disease (AD) and Lewy body disease (LBD), the two most common causes of neurodegenerative dementia with similar clinical manifestations, both show impaired visual attention and altered eye movements. However, prior studies have used structured tasks or restricted stimuli, limiting the insights into how eye movements alter and differ between AD and LBD in daily life. OBJECTIVE: We aimed to comprehensively characterize eye movements of AD and LBD patients on naturalistic complex scenes with broad categories of objects, which would provide a context closer to real-world free viewing, and to identify disease-specific patterns of altered eye movements...

BACKGROUND: The Lateral Organ Boundaries Domain (LBD) gene family is a family of plant-specific transcription factors (TFs) that are widely involved in processes such as lateral organ formation, stress response, and nutrient metabolism. However, the function of LBD genes in maize remains poorly understood. METHODS AND RESULTS: In this study, a total of 49 ZmLBD genes were identified at the genome-wide level of maize, they were classified into nine branches based on phylogenetic relationships, and all of them were predicted to be nuclear localized...

Overexpression of MdLBD3 in Arabidopsis reduced sensitivity to salt and drought stresses and was instrumental in promoting early flowering. Salt and drought stresses have serious effects on plant growth. LATERAL ORGAN BOUNDARY DOMAIN (LBD) proteins are a plant-specific transcription factors (TFs) family and play important roles in plants in resisting to abiotic stress. However, about the function of LBDs in apple and other woody plants is little known. In this study, protein sequences of the LBD family TFs in apples were identified which contained conserved LOB domains...

AIMS: Hirano bodies (HBs) are eosinophilic pathological structures with two morphological phenotypes commonly found in the hippocampal CA1 region in Alzheimer's disease (AD). This study evaluated the prevalence and distribution of HBs in AD and other neurodegenerative diseases. METHODS: This cross-sectional study systematically evaluated HBs in a cohort of 193 cases with major neurodegenerative diseases, including AD (n = 91), Lewy body disease (LBD, n = 87), progressive supranuclear palsy (PSP, n = 36), multiple system atrophy (MSA, n = 14) and controls (n = 26)...

UNLABELLED: The gene family known as the Lateral Organ Boundary Domain ( LBD ) is responsible for producing transcription factors unique to plants, which play a crucial role in controlling diverse biological activities, including their growth and development. This research focused on examining Cerasus humilis ' ChLBD gene, owing to its significant ecological, economic, and nutritional benefits. Examining the ChLBD gene family's member count, physicochemical characteristics, phylogenetic evolution, gene configuration, and motif revealed 41 ChLBD gene family members spread across 8 chromosomes, with ChLBD gene's full-length coding sequences (CDSs) ranging from 327 to 1737 base pairs, and the protein sequence's length spanning 109 ( ChLBD30 )-579 ( ChLBD35 ) amino acids...

The androgen receptor AR antagonists, such as enzalutamide and apalutamide, are efficient therapeutics for the treatment of prostate cancer (PCa). Even though they are effective at first, resistance to both drugs occurs frequently. Resistance is mainly driven by aberrations of the AR signaling pathway including AR gene amplification and the expression of AR splice variants (e.g. AR-V7). This highlights the urgent need for alternative therapeutic strategies. Here, a total of 24 compounds were synthesized and biologically evaluated to disclose compound 20i, exhibiting potent AR antagonistic activities (IC50  = 172...

The production of androst-4-ene-3,17-dione (AD) by the steroidal microbial cell factory requires transcription factors (TFs) to participate in metabolic regulation. However, microbial cell factory lacks effective TFs that can respond to AD in its metabolic pathway. Additionally, finding and obtaining natural TFs that specifically respond to AD is a complex and onerous task. In this study, we devised an artificial TF that responds to AD, termed AdT, based on structure-guided molecular dynamics (MD) simulation...

Cognitive dysfunction and dementia are critical symptoms of Lewy Body dementias (LBD). Specifically, alpha-synuclein (αSyn) accumulation in the hippocampus leading to synaptic dysfunction is linked to cognitive deficits in LBD. Here, we investigated the pathological impact of αSyn on hippocampal neurons. We report that either αSyn overexpression or αSyn pre-formed fibrils (PFFs) treatment triggers the formation of cofilin-actin rods, synapse disruptors, in cultured hippocampal neurons and in the hippocampus of synucleinopathy mouse models and of LBD patients...

Neuropathological assessment was conducted on 1630 subjects, representing 5% of all the deceased that had been sent to the morgue of Uppsala University Hospital during a 15-year-long period. Among the 1630 subjects, 1610 were ≥41 years of age (range 41 to 102 years). Overall, hyperphosphorylated (HP) τ was observed in the brains of 98% of the 1610 subjects, and amyloid β-protein (Aβ) in the brains of 64%. The most common alteration observed was Alzheimer disease neuropathologic change (ADNC) (56%), followed by primary age-related tauopathy (PART) in 26% of the subjects...

BACKGROUND: The GPNMB single-nucleotide polymorphism rs199347 and GBA1 variants both associate with Lewy body disorder (LBD) risk. GPNMB encodes glycoprotein nonmetastatic melanoma protein B (GPNMB), a biomarker for GBA1-associated Gaucher's disease. OBJECTIVE: The aim of this study was to determine whether GPNMB levels (1) differ in LBD with and without GBA1 variants and (2) associate with rs199347 genotype. METHODS: We quantified GPNMB levels in plasma and cerebrospinal fluid (CSF) from 124 individuals with LBD with one GBA1 variant (121 plasma, 14 CSF), 631 individuals with LBD without GBA1 variants (626 plasma, 41 CSF), 9 neurologically normal individuals with one GBA1 variant (plasma), and 2 individuals with two GBA1 variants (plasma)...

4-Nonylphenol (4-NP), a para -substituted phenolic compound with a straight or branched carbon chain, is a ubiquitous environmental pollutant and food contaminant. 4-NP, particularly the branched form, has been identified as an endocrine disruptor (ED) with potent activities on estrogen receptors. Constitutive Androstane Receptor (CAR) is another crucial nuclear receptor that regulates hepatic lipid, glucose, and steroid metabolism and is involved in the ED mechanism of action. An NP mixture has been described as an extremely potent activator of both human and rodent CAR...

Alchemilla vulgaris L., Trifolium pratense L. and Glycyrrhiza glabra L. are important remedies in traditional medicine, known for many usages, including treating gynecological diseases. Despite folkloric use of the plant materials, there is a lack of scientific data to support their therapeutic application. The aims of the present study were to evaluate the relative binding affinities (RBAs) of plant-derived phytoestrogens for estrogen receptor β (ERβ) using fluorescent biosensor in yeast and to apply this assay for the assessment of the potential of plant materials towards ERs and treatment of estrogen-related disorders...

The disease-specific accumulation of pathological proteins has long been the major focus of research in neurodegenerative diseases (ND), including Alzheimer's disease (AD) and related dementias (RD), but the recent identification of a multitude of genetic risk factors for ND in immune-associated genes highlights the importance of immune processes in disease pathogenesis and progression. Studies in animal models have characterized the local immune response to disease-specific proteins in AD and ADRD, but due to the complexity of disease processes and the co-existence of multiple protein pathologies in human donor brains, the precise role of immune processes in ND is far from understood...

Introduction: Low back disorder (LBD) is a major cause of disability worldwide. Inflammation results in proliferation of cytokines or consequent degradation products (collectively known as Inflammatory Biomarkers) that activate pain pathways which can result in non-specific LBD. This systematic review and meta-analysis aim to evaluate the relationship between inflammatory biomarkers and clinical outcomes in patients with LBD. Methods: Three online databases were searched. Four RCTs and sixteen observational studies with 1142 LBD patients were analysed...

Previously, we established a homogeneous assay for membrane progesterone receptor alpha (mPRα) ligands by conjugating semiconductor nanoparticles known as graphene quantum dots (GQDs) to mPRα. When mixed with a progesterone-BSA-fluorescein isothiocyanate conjugate (P4-BSA-FITC), fluorescence occurred by fluorescence resonance energy transfer (FRET) but was reduced by the ligand-receptor binding activity. The established way showed ligand specificity as mPRα protein. In this study, we tried to establish the same way for nuclear progesterone receptor (Pgr)...

Reactive astrogliosis accompanies the two neuropathological hallmarks of Alzheimer's disease (AD)-Aβ plaques and neurofibrillary tangles-and parallels neurodegeneration in AD and AD-related dementias (ADRD). Thus, there is growing interest in developing imaging and fluid biomarkers of reactive astrogliosis for AD/ADRD diagnosis and prognostication. Monoamine oxidase-B (MAO-B) is emerging as a target for PET imaging radiotracers of reactive astrogliosis. However, a thorough characterization of MAO-B expression in postmortem control and AD/ADRD brains is lacking...

BACKGROUND: Parkinson's disease (PD) is a condition that affects movement and is usually seen in those over the age of 50. It is caused by the death of dopaminergic neurons, particularly in the substantia nigra. PD has shifted from being perceived as an uncommon condition to a significant neurological illness, mostly due to the increasing number of elderly individuals and the impact of environmental factors. Parkinson's plus syndromes, such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and vascular Parkinsonism (VaP), provide difficulties in distinguishing them clinically from PD since they have similar characteristics...

Thyroid hormone receptor β (THRβ) is a member of the nuclear receptor superfamily of ligand-modulated transcription factors. Upon ligand binding, THRβ sequentially recruits the components of transcriptional machinery to modulate target gene expression. In addition to regulating diverse physiological processes, THRβ plays a crucial role in hypothalamus-pituitary-thyroid axis feedback regulation. Anomalies in THRβ gene/protein structure are associated with onset of diverse disease states...

The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. Here we develop and validate a method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and use solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise a mixture of single protofilament and two protofilament fibrils with very low twist. The protofilament fold is highly similar to the fold determined by a recent cryo-electron microscopy study for a minority population of twisted single protofilament fibrils extracted from LBD tissue...

The farnesoid X receptor (FXR) has been recognized as a potential drug target for the treatment of non-alcoholic fatty liver disease (NAFLD). FXR agonists benefit NAFLD by modulating bile acid synthesis and transport, lipid metabolism, inflammation, and fibrosis pathways. However, there are still great challenges involved in developing safe and effective FXR agonists. To investigate the critical factors contributing to their activity on the FXR, 3D-QSAR molecular modeling was applied to a series of isoxazole derivatives, using comparative molecular field analysis (CoMFA (q2 = 0...