Daily Med Bites - 22/05/2025

Dear reader, here are the summaries of some of the latest papers from PubMed.

Cardiovascular Risk Factors:

• Source: The study finds that the triglyceride-glucose index (TyG index) is associated with an increased risk of cardiovascular mortality, even when accounting for non-cardiovascular mortality as a competing risk.

• Source: Higher TyG index levels are associated with increased mortality risk, particularly in metabolically unhealthy obese individuals, regardless of obesity status.

• Source: Higher triglyceride-glucose index (TyG) is associated with worse anthropometric and metabolic profiles, as well as adverse pregnancy outcomes in Chinese women with PCOS.

• Source: TyG-WC index is a significant predictor of NAFLD risk, indicating its potential value in assessing insulin resistance and identifying individuals at risk for developing NAFLD.

• Source: The study finds that higher BMI may be associated with lower mortality risk in CRD patients, potentially mediated by the triglyceride-glucose index.

• Source: The study reveals that Stress Hyperglycemia Ratio (SHR) is associated with both short-term and long-term prognosis in patients undergoing CABG, highlighting its importance as a prognostic indicator across different glucose metabolic states.

• Source: The study found that certain dietary patterns are associated with an increased risk of type 2 diabetes mellitus (T2DM) in Chinese adults, with higher HOMA or TyG indices acting as intermediary factors linking diet to T2DM risk.

• Source: Normal glucose tolerance individuals with elevated 1-hour post-load plasma glucose have lipid profiles associated with increased cardiovascular disease risk, suggesting they are not low-risk despite having normal glucose tolerance.

• Source: The study found that a higher triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) is associated with an increased risk of left ventricular hypertrophy in hypertensive patients among the Han Chinese population.

• Source: The study finds a significant association between higher atherogenic index of plasma (AIP) and increased risk of all-cause and cardiovascular mortality in individuals with Cardiovascular-Kidney-Metabolic (CKM) syndrome, highlighting AIP as a potential biomarker for predicting mortality risk in this population.

• Source: Modified TyG indices are strongly associated with MAFLD in adolescents and can predict MAFLD risk when combined with anthropometric measures.

• Source: Elevated Lp(a) levels modify the association between diabetes and coronary heart disease, increasing the risk in primary prevention settings.

• Source: Obesity increases the risk of adverse cardiovascular outcomes in metabolically healthy individuals with coronary artery disease.

Alzheimer’s Disease:

• Source: Immunomodulatory mechanisms play a crucial role in Alzheimer’s disease pathogenesis, and targeting immune pathways may offer novel therapeutic strategies to mitigate neurodegeneration.

• Source: Development of anti-Aβ immunotherapies marks a breakthrough as the first disease-modifying therapy for Alzheimer’s Disease, advancing both basic research and translational science.

• Source: Genetic evidence elucidates how peripheral immune cells mediate IL-6’s effects on Alzheimer’s disease pathogenesis, offering new insights into AD mechanisms.

• Source: Astrocytes play a critical role in maintaining ion homeostasis, which is disrupted in Alzheimer’s disease, affecting neuronal function and contributing to neurodegeneration.

• Source: The study identifies DDX6 as a protein that binds to Aβ oligomers and promotes their formation, leading to neurotoxicity. Blocking DDX6 reduces Aβ oligomer neurotoxicity both in vitro and in vivo, suggesting it could be a potential therapeutic target for Alzheimer’s disease.

• Source: Non-transgenic rodent models are crucial for preclinical research in Alzheimer’s disease, providing insights into pathophysiology and potential treatments.

• Source: Autophagy modification through mTOR inhibition, AMPK activation, PDE4 inhibition, and TFEB upregulation can improve neuronal survival and cognitive function in Alzheimer’s disease models.

• Source: The study demonstrates that using transferrin-decorated extracellular vesicles to deliver berberine and palmatine can effectively target microglia, reduce neuroinflammation, clear amyloid β-protein aggregates, and improve cognitive functions in Alzheimer’s disease model mice.

• Source: The study shows that long-term treatment with fucoxanthin can prevent cognitive decline in transgenic Alzheimer’s disease models, providing insights into its anti-neuroinflammatory mechanism.

• Source: The study identifies intermediate states of aging in hippocampal microglia and shows that these states can be modulated by specific signaling pathways, providing insights into the progression from homeostasis to dysfunction during aging.

• Source: SGLT2 inhibition with Enavogliflozin improves cognitive function and reduces Alzheimer’s disease pathology by enhancing synaptic plasticity, increasing acetylcholine levels, decreasing Aβ plaques, and mitigating neuroinflammation through microglial activation.

• Source: Nasal-foralumab reduced microglial activation in brain regions with high amyloid deposition in a patient with Alzheimer’s disease, as shown by PET imaging.

• Source: The paper’s main contribution is developing human model systems that replicate both the pathological features and transcriptional landscapes in neurons, astrocytes, and microglia during early Aβ exposure in Alzheimer’s disease, thereby advancing understanding of early disease mechanisms.

• Source: Thioredoxin-1 overexpression inhibits NLRP3-mediated pyroptosis and protects against Aβ-induced neurocytotoxicity in Alzheimer’s disease models.

• Source: The paper highlights the multifaceted roles of apolipoprotein E (apoE) in Alzheimer’s disease pathogenesis and emphasizes recent discoveries that could lead to therapeutic strategies targeting apoE-mediated pathways, particularly for genetically at-risk populations.

• Source: The main contribution of this paper is demonstrating that ZJQ-3F protects against Alzheimer’s disease in APP/PS1/Tau transgenic mice by inhibiting AChE, BACE1, and GSK3β.

• Source: Development of a mouse model that combines epilepsy and Alzheimer’s disease through mitochondrial inhibition, revealing shared neurochemical alterations and potential therapeutic targets.

• Source: Microglia-driven inflammation can initiate and propagate both tauopathy and synucleinopathy, leading to widespread neurodegeneration and behavioral deficits in mice.

• Source: The take-home message of this paper is that Coenzyme Q10 (CoQ10) shows promise as a neuroprotective agent in Alzheimer’s disease by reducing oxidative stress and neuroinflammation, but further human trials are needed to clarify its therapeutic potential due to mixed results from preclinical studies.

• Source: Chronic psychological stress exacerbates neurobehavioral and cognitive impairments in an Alzheimer’s disease mouse model, but supplementation with indole-3-propionate (IPA) mitigates these effects by reducing inflammation through the gut-immune-brain axis.

• Source: Traffic-related air pollution affects Alzheimer’s disease by reducing esterified lipid pools, which are crucial for producing free bioactive pro-resolving lipids needed to resolve brain inflammation.

• Source: Guanidine-rich lipids trigger selective chaperone-mediated autophagy to degrade amyloid precursor protein in neurons, potentially improving Alzheimer’s disease treatment.

• Source: Oxytosis/ferroptosis occurs in Alzheimer’s disease brains, suggesting it may be a therapeutic target for AD.

• Source: ELK1 increases in Alzheimer’s disease and its inhibition reduces amyloid-beta generation and memory impairments by enhancing PS1 degradation through SYVN1.

• Source: Ion channel dysregulation contributes significantly to Alzheimer’s disease pathophysiology, suggesting potential for ion channels as therapeutic targets.

• Source: Quercetin protects against early Alzheimer’s disease by inhibiting the NLRP3 inflammasome pathway in response to stress.

• Source: LINC00672 influences autophagy mechanisms in Alzheimer’s disease, potentially offering new therapeutic targets.

• Source: β-hydroxybutyrate (BHB) improves cognitive function and reduces neurodegeneration in an Alzheimer’s disease-like model by restoring chaperone-mediated autophagy, inhibiting inflammation, and normalizing neurotransmitter levels.

• Source: The paper identifies a novel role for lipid droplets (specifically PLIN3+) in human astrocytes, showing they facilitate the processing and transfer of MHCII molecules, which is relevant to neuroinflammation in Alzheimer’s disease.

• Source: Olfactory neuronal precursors derived from the olfactory neuroepithelium offer a promising, non-invasive model for biomarker discovery in Alzheimer’s disease, enabling early detection and personalized management.

• Source: The study demonstrates that electroacupuncture (EA) improves cognitive function in mice with Alzheimer’s disease by modulating histone deacetylase 3 (HDAC3), enhancing synaptic plasticity, and regulating NMDA receptors in the hippocampus.

• Source: The PSEN1 M139I mutation in early-onset Alzheimer’s disease increases Aβ42/40 levels and apoptosis by downregulating NOTCH-1 through the microRNA-34a pathway.

• Source: Gut-derived propionate reduces reactive astrocytosis and Alzheimer’s disease-associated amyloid plaques by decreasing peripheral Th17 cells and IL-17 release, suggesting potential therapeutic strategies for AD.

• Source: The study identifies common and distinct molecular changes in dopamine and GABA neurons during aging, including increased inflammation, upregulation of pro-survival pathways, and sex-specific differences linked to neurodegenerative disease susceptibility.

• Source: Human Alzheimer’s disease seeds induce more aggressive amyloid pathology compared to mouse seeds, but mouse seeds trigger more tau pathology and impair microglial response around plaques. Different factors influence the progression of amyloid and tau pathology in AD.

• Source: The study identifies distinct MRI patterns of cortical atrophy associated with different clinical phenotypes of Alzheimer’s disease and their relationships to biomarkers like amyloid-beta, phosphorylated tau, neuro-axonal degeneration, and microvascular deterioration.

• Source: The key finding of this paper is that Amyloid β (Aβ) can enhance stress resistance in neurons of C. elegans through heat shock protein activation and neuropeptide signaling, suggesting a beneficial role for Aβ beyond its detrimental effects associated with Alzheimer’s Disease.

• Source: The paper reports the discovery of a novel α4/7-conotoxin (LvID) that targets α7 nicotinic acetylcholine receptors, which are important in cognitive function and implicated in various diseases such as Alzheimer’s disease.

• Source: The study demonstrates that voclosporin can improve neurological outcomes and protect the blood-brain barrier by reducing inflammation and promoting beneficial microglia/macrophage polarization in mice treated with rtPA, suggesting potential for combined therapy to mitigate hemorrhagic transformation.

• Source: VLP-based vaccines targeting phosphorylated tau epitopes can induce effective immune responses and improve cognitive function in a mouse model of FTD, with the Ser396/Ser404 vaccine showing particular efficacy.

• Source: Identification of T1R2/T1R3 as the receptor that regulates voltage-gated sodium channels through interaction with amyloid beta peptides, linking Aβ to neuronal hyperactivity in Alzheimer’s disease.

• Source: The study shows that Taurine combined with LED irradiation improves mitochondrial function in SH-SY5Y cells exposed to oxidative stress, suggesting a potential therapeutic approach for Alzheimer’s disease.

• Source: CGRP plays dual roles in neurodegenerative diseases, acting as both a protective factor and a potential contributor to neuronal damage depending on its context, highlighting the need for targeted therapeutic approaches that harness its benefits while avoiding adverse effects.

• Source: DUBs play critical roles in maintaining BBB integrity and neuroprotection, with potential for therapeutic interventions in neurodegenerative disorders through targeted agonists and inhibitors.

• Source: Characterization of patients initiating lecanemab treatment in real-world settings shows diverse clinical and demographic profiles, indicating varied applicability and challenges in early Alzheimer’s disease management.

• Source: Lipoamide prevents aberrant stress granule condensation and improves symptoms in neurodegenerative disease models by stabilizing specific intrinsically disordered proteins and modulating redox regulation.

• Source: The key takeaway is that age at symptom onset for Autosomal Dominant Alzheimer’s Disease varies among different genetic mutations, with PSEN1 mutations leading to earlier onset compared to PSEN2 and APP mutations. This variability is crucial for understanding disease mechanisms and developing targeted interventions.

• Source: Microglial IKKβ signaling drives pro-inflammatory responses after spinal cord injury, influencing both central and peripheral immune activity, and inhibiting this signaling can mitigate these effects.

That’s enough for today, see you tomorrow!

As always, these extremely reduced summaries may be incomplete or inexact in some aspects. Make sure to always read the papers of interest.

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