Telocinobufagin suppresses malignant metastasis of undifferentiated thyroid carcinoma via modulation of the LARP1-mTOR pathway.

Metastasis is the trigger of death in anaplastic thyroid cancer (ATC) patients, yet the specific mechanisms at play are still largely enigmatic. While the involvement of LARP1 in the metastatic process of various cancers has been documented, there is a noticeable gap in the literature regarding its potential influence on ATC metastasis. Molecular studies probed LARP1 expression within ATC cells, with subsequent in vitro experiments examining the effects of LARP1 on ATC cell metastasis and the mTOR signaling cascade.

EZH2-mediated downregulation of miR-155-5p contributes to prostate cancer cell malignancy through SMAD2 and TAB2.

miR-155 exhibits variable expression in different tumors and fulfills diverse biological roles. However, specific molecular mechanisms by which miR-155-5p, which is under-expressed in prostate cancer (PCa), operates are yet to be elucidated. The role of the enhancer of zeste 2 (EZH2)/miR-155-5p axis in PCa was determined by using bioinformatics tools and performing luciferase reporter assay, chromatin immunoprecipitation PCR, CCK-8 assays, cell migration and invasion assays, RNA isolation, reverse transcription quantity (RT-qPCR) and Western blot.

Biomarkers.

Background: Apolipoproteins and cortical morphology are closely associated with memory complaints, and both may contribute to the development of Alzheimer's disease.

Method: A total of 97 patients from the University of Electronic Science and Technology (UESTC) (n=42) and the Fourth People's Hospital of Chengdu (FPHC) (n=55) were grouped based on recruitment location, and underwent neuropsychological tests. ApoB, ApoA1, ApoB/ApoA1, plasma Alzheimer's biomarker, apolipoprotein E (ApoE) genotyping, 3T magnetic resonance imaging.

Biomarkers.

Background: It is challenging to distinguish which subcortical ischemic vascular disease (SIVD) patients will present with cognitive impairment. A blood-based biomarker to distinguish SIVD patients with cognitive impairment would be superior to neuropsychological measures and neuroimaging measures in terms of cost, time, and feasibility for repeated measures. Metabolomics profiling studies could help identify blood-based biomarkers for SIVD patients with cognitive impairment.

Biomarkers.

Background: Existing biomarkers including cerebrospinal fluid and positron emission tomography for Alzheimer's disease (AD) diagnosis are relatively invasive and expensive. Application of exhaled breath collection and volatile organic compound (VOC) detection for AD diagnosis remains unclear.

Method: In this cross-sectional study, high-pressure photon ionization time-of-flight mass spectrometry (HPPI-ToF-MS) was used to detect VOCs from breath in three datasets and patients diagnosed as Parkinson's disease (PD).

Biomarkers.

Background: The heart-brain connection has been proposed to correlate cardiac disorders with brain health. However, the associations between subclinical alterations in cardiac structure or function and Alzheimer's disease (AD) pathologies haven't been fully elucidated. This study aimed to delineate the interrelationships between the subclinical alterations in the left heart, cerebrospinal fluid (CSF) AD biomarkers, and cognition.

Biomarkers.

Background: Previous studies have found that AD-related plasma markers are associated with Aβ deposition, but the specific effects remain unclear.

Method: Data were obtained from the Longitudinal Study of Cognitive Decline in China (SILCODE). Comprehensive neuropsychological assessments, MRI, plasma samples, and amyloid positron-emission tomography (Aβ-PET) data were collected.

Biomarkers.

Background: An urgent need exists for minimally invasive testing for accurate detection of Alzheimer's disease (AD). Circulating microRNAs (miRNAs) have been investigated as a promising candidate biomarker for AD diagnosis and prediction because of their involvement in multiple brain signaling pathways in both health and disease. This study developed and validated a serum miRNA panel in discriminating clinically diagnosed AD from age-matched cognitively healthy controls.

Biomarkers.

Background: Subjective cognitive decline (SCD), in the absence of objective cognitive impairment, may be the first symptomatic manifestation of Alzheimer's disease (AD). Previous studies have suggested that its combination with amyloid-positivity (Aβ+) may represent stage 2 AD, and is associated with a higher risk of future cognitive decline. Here, we aim to (1) confirm this using the plasma Aβ42/40 ratio, and (2) test whether the addition of plasma phospho-tau181 (ptau, a marker of Aβ and tau pathology) could help refine the prediction of future cognitive decline in SCD patients.

Biomarkers.

Background: The regulatory role of Trimethylamine-N-oxide (TMAO) for cognition from the perspective of microbiota-gut-brain (MGB) axis in AD remains unclear.

Method: In clinical cohort study for effects of 24-week computerized cognitive training (CCT), registered on clinicaltrials.gov (NCT06094452), plasma TMAO levels were quantified using ELISA in MCI (n=39) and mild AD patients (n=35).

Biomarkers.

Background: We currently lack in the dementia field accurate, noninvasive, quick, and affordable screening tools for brain dysfunctions associated with early subtle risk of mild cognitive impairment (MCI). Our Kentucky aging cohort demonstrates that asymptomatic older individuals with MCI-like frontal memory-related brainwave patterns convert to MCI within a short 5-year period, as opposed to individuals with NC-like patterns (1) that remain normal 10 years later (2). Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer's disease (3).

Biomarkers.

Background: White matter hyperintensities (WMH) were reported to contribute to the thinning of regional cortex connected to WMH in cerebral small vessel disease. However, the relationship between WMH and regional changes in WMH-connected cortex in Alzheimer's disease (AD) remains unclear. The objective of this study is to investigate the association between WMH and regional cortical thickness, amyloid and tau deposition, and synaptic density changes in the WMH-connected cortex.

Biomarkers.

Background: Alzheimer's disease is a common neurodegenerative disease that affects the lives of millions of people worldwide. In our study, we aim to evaluate the effectiveness and accuracy of the latest automated brain volume analysis method for GM and WM analysis in health control and patients with AD and to compare optimized cut-off values for both regions between subjects.

Method: The original baseline scans from 37 HC (HC) and 39 mild AD patients downloaded from ADNI.

Biomarkers.

Background: In the context of Alzheimer's disease (AD), blood-based biomarkers have become increasingly important for various clinical purposes, such as screening patients and tracking the progression of the disease. Tau is a protein that stabilizes microtubules in nerve cells. In AD, different isoforms of tau become hyperphosphorylated, leading to the formation of neurofibrillary tangles, which are a key pathological feature of the AD.

Biomarkers.

Background: Alzheimer's disease (AD) is associated with substantial synaptic loss potentially due to synaptotoxicity of fibrillar tau, but the association between tau deposition and synaptic loss remains unclear. Based on previous observations that pathology spreads preferentially between closely connected regions, we tested in the current multi-PET tracer study the hypothesis that synaptic loss propagates to regions closely connected to epicenters of high tau accumulation.

Method: We assessed 18F-SynVesT-1 PET as a measure of synaptic vesicle glycoprotein 2A (SV2A), and 18F-flortaucipir tau-PET in fourty-five 18F-florbetapir-PET-positive (Aβ+) subjects with MCI or AD dementia, and 23 cognitivly normal (CN) Aβ- controls.

Biomarkers.

Background: The role of circulating metabolome in cognitive impairment is limited and inconclusive. We aimed to identify plasma metabolites associated with cognitive impairment and evaluate the added predictive capacity of metabolite biomarkers on incident cognitive impairment beyond traditional risk factors.

Method: In the community-based Rugao Longevity and Ageing Study (RuLAS), plasma metabolome was profiled by nuclear magnetic resonance (NMR) spectroscopy.

Biomarkers.

Background: Hypertension is widely prevalent and independently increases the risk of dementia. Advances in high-throughput plasma proteomics analyzed may offer new opportunities to improve risk stratification for these patients.

Method: This study involved a proteomic analysis of plasma samples collected during the baseline recruitment of participants in the UK Biobank.

Biomarkers.

Background: Alzheimer disease (AD) plasma biomarkers change in the preclinical stage of AD. However, the robustness of the discrimination performance of these biomarkers, as well as their association with longitudinal primary pathology (amyloid and tau) changes, is less understood. We aimed to determine the ability of baseline and longitudinal plasma amyloid-β (Aβ)42/40, p-tau181, GFAP and NfL to detect primary pathology in CU individuals at risk of AD.

Biomarkers.

Background: Alzheimer's disease (AD), a complex and polygenic disease with a considerable hereditary component (60-80%), is a progressive neurodegenerative disorder characterized by concealed onset, and individuals often have significant cognitive impairment and histopathological changes in the brain before overt clinical diagnosis. However, the correlations between genetic risk for Alzheimer's disease (AD) with comprehensive brain regions at a regional scale are still not well understood. We aim to explore whether these associations vary across different age stages.

Biomarkers.

Background: The structural brain alterations for subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are poorly defined. We sought to characterize grey matter volume (GMV) and cortical thickness associated with SCD and MCI among rural-dwelling older adults in China.

Method: This population-based cross-sectional study included 1072 dementia-free participants derived from the brain MRI substudy of MIND-China in 2018-2020.

Biomarkers.

Background: Growing evidence indicates that people with neurodegenerative diseases have altered metabolic status, but the association between metabolic age (MetAge), as assessed by circulating plasma metabolomics, and dementia remains unclear. We aimed to investigate the association between MetAge and risk of dementia and to explore whether genetic background plays a role in these associations.

Method: From the UK Biobank, 153,436 dementia-free adults aged ≥55 (mean age 62.

Biomarkers.

Background: Neurofilament light chain protein (NfL) in cerebrospinal fluid (CSF) reflects the severity of neurodegeneration, with its altered concentrations discovered in Parkinson's disease (PD) and Parkinson's disease dementia (PD-D).

Method: A total of 259 people were recruited in this study, including 85 healthy controls (HC) and 174 neonatal PD patients from the Parkinson's Progression Markers Initiative (PPMI). Multiple linear regression and linear mixed effects models were used to examine the associations of baseline/ longitudinal CSF NfL with cognitive decline and other CSF biomarkers.

Tröger's base-embedded macrocycles with chirality.

The birth and development of supramolecular chemistry have heralded a new era, where macrocycles have become an irreplaceable research tool. Therefore, the construction of novel macrocycles has become a hot spot. Tröger's base (TB), as a fragment with both rigidity and chirality, promises tremendous potential in the realm of supramolecular chemistry, and its unique properties continue to motivate researchers to explore its inclusion in macrocycles.

Biomarkers.

Background: About 50-90% people with dementia would develop behavioral disturbances, namely, behavioral and psychological symptoms of dementia (BPSD). Antipsychotic medications are widely used to control severe BPSD symptoms which suffers serious safety risks. It is challenge for individualized precise prediction of antipsychotic drug doses.