All kinds of mutagenic factors may cause physiological, biochemical and genetic changes of all organisms. To characterize their characteristic biology effects, the concept of Relaxation Time (RT) was introduced for the first time, and the specific process was as follows. After mutation of organisms, the offsprings will be continuingly cultured (or cultivated) to the next generation (Rx). Once a biological effect began to show no significant difference compared to the untreated controls, the Rx was defined as the RT of the effect. In this paper, three kinds of mutagenic factors were selected to treat the seeds or seedlings of Astragalus sinicus L., subsequently, the corresponding RT was calibrated. The results showed that the RT was diverse not only among different biological effects but also among different mutagenic factors. For the RT of chemical mutagens and gamma rays, most of which are concentrated on R, whereas the heavy ion beams have significant differences among different tracks. Among biological effects, the SOD activity and superoxide anion free radical content in the Peak region are more prominent, and their RT reaches R and R, respectively. Thus, the RT may characterize the characteristic biological effects from differently mutagenic factors.
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http://dx.doi.org/10.1038/s41598-020-70600-2 | DOI Listing |
Alzheimers Dement
December 2024
Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, North Holland, Netherlands.
The lack of an in-vivo pathology marker for synuclein pathology has been a long standing challenge for dementia for Lewy bodies (DLB) research. This issue is critically important for phase II trials, which are often small, requiring the precise measurement of the biological effects, whether disease modifying or symptomatic. Recent advances have enabled the determination of alpha-synuclein pathology status with CSF measurements, using aggregation assays [RT-QUIC].
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, Beijing, China.
Background: The DL-3-n-butylphthalide (NBP), a multi-target neuroprotective drug, improving cognitive impairment in patient with vascular cognitive impairment has been confirmed. The efficacy of NBP in patients with cognitive impairment due to Alzheimer's disease (AD) remains unknown. This study aimed to evaluate the efficacy and safety of NBP in patients with mild cognitive impairment (MCI) due to AD though a clinical randomized controlled trail.
View Article and Find Full Text PDFAlzheimers 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 PDFAlzheimers Dement
December 2024
Xuanwu Hospital, Capital Medical University, Beijing, Beijing, China.
Background: Effective early intervention of mild cognitive impairment (MCI) is the key for preventing dementia. However, there is currently no drug for MCI. As a multi-targeted neuroprotective agent, butylphthalide has been demonstrated to repair cognition in patients with vascular cognitive impairment, and has the potential to treat MCI due to Alzheimer's disease (AD).
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