Human activities have changed the global concentration of potentially toxic elements (PTEs) and significantly altered the marine ecosystem. Little is known about the concentrations of these PTEs around Hainan Island in China, or their distribution and human health risks. Understanding the variability of PTEs in marine sediments and how they accumulate is important not only for biodiversity and ecological conservation, but also for management of aquatic natural resources and human health risk assessments. This study showed that the concentrations of six PTEs (Cd, Cu, Zn, As, Pb, and Hg), sampled in nine different cities, were linked to human activities. In order to understand the ecological risks associated with PTE pollution, we calculated the contamination factor (CF), enrichment factor (EF), pollution load index (PLI), and geo-accumulation index (Igeo) of each element in each city. These indicators suggest that the pollution of Cd and Zn in the sediments of these cities is higher than that of the other PTEs. We also carried out a human health risk assessment which demonstrated the carcinogenic effects of Zn on children and adults in ChengMai, while Pb showed non-carcinogenic effects at all the studied sites, suggesting that Zn pollution in the sediments of ChengMai may pose human health risks. We would therefore advise that follow-up studies endeavor to monitor the levels of PTEs in the flora and fauna of these cities.
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http://dx.doi.org/10.1016/j.marpolbul.2021.113278 | DOI Listing |
Alzheimers Dement
December 2024
The University of Texas Health Science Center at Houston, Houston, TX, USA.
Background: Developing drugs for treating Alzheimer's disease (AD) has been extremely challenging and costly due to limited knowledge on underlying biological mechanisms and therapeutic targets. Repurposing drugs or their combination has shown potential in accelerating drug development due to the reduced drug toxicity while targeting multiple pathologies.
Method: To address the challenge in AD drug development, we developed a multi-task machine learning pipeline to integrate a comprehensive knowledge graph on biological/pharmacological interactions and multi-level evidence on drug efficacy, to identify repurposable drugs and their combination candidates RESULT: Using the drug embedding from the heterogeneous graph representation model, we ranked drug candidates based on evidence from post-treatment transcriptomic patterns, mechanistic efficacy in preclinical models, population-based treatment effect, and Phase 2/3 clinical trials.
Alzheimers Dement
December 2024
Case Western Reserve University, Cleveland, OH, USA.
Background: Traumatic Brain Injury (TBI) is one of the most common nonheritable causes of Alzheimer's disease (AD). However, there is lack of effective treatment for both AD and TBI. We posit that network-based integration of multi-omics and endophenotype disease module coupled with large real-world patient data analysis of electronic health records (EHR) can help identify repurposable drug candidates for the treatment of TBI and AD.
View Article and Find Full Text PDFBackground: Although investment in biomedical and pharmaceutical research has increased significantly over the past two decades, there are no oral disease-modifying treatments for Alzheimer's disease (AD).
Method: We performed comprehensive human genetic and multi-omics data analyses to test likely causal relationship between EPHX2 (encoding soluble epoxide hydrolase [sEH]) and risk of AD. Next, we tested the effect of the oral administration of EC5026 (a first-in-class, picomolar sEH inhibitor) in a transgenic mouse model of AD-5xFAD and mechanistic pathways of EC5026 in patient induced Pluripotent Stem Cells (iPSC) derived neurons.
Alzheimers Dement
December 2024
National Institute on Aging, NIH, Baltimore, MD, USA.
Background: Epidemiological studies report an elevated risk of neurodegenerative disorders, particularly Parkinson's disease (PD), in patients with type 2 diabetes mellitus (T2DM) that is mitigated in those prescribed incretin mimetics or dipeptidyl peptidase 4 inhibitors (DPP-4Is). Incretin mimetic repurposing appears promising in human PD and Alzheimer's disease (AD) clinical trials. DPP-4Is are yet to be evaluated in PD or AD human studies.
View Article and Find Full Text PDFBackground: Progranulin (PGRN), a glycoprotein secreted by microglia and neurons, regulates lysosomal function, neuroinflammation, and has neurotrophic effects. Variants in the granulin gene (GRN) that cause a reduction of PGRN in plasma and cerebrospinal fluid (CSF) are associated with an increased risk of Alzheimer's disease (AD). The sortilin receptor (SORT1) on neurons and microglia regulates PGRN degradation.
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