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Ligustilide, the main lipophilic component of Radix angelicae sinensis, has been shown to ameliorate cognitive dysfunction in a few Alzheimer's disease mouse models, but its mechanism is not fully understood. In this study, we employed 7-month-old APP/PS1 mice to explore whether LIG is able to protect against Alzheimer's disease progression. The Morris water maze and Y-maze test results showed that eight weeks of intragastric administration of LIG (10 mg/kg, 40 mg/kg) every day improved memory deficit in APP/PS1 mice. The thioflavin-S staining and Western blot results (Aβ1-42 monomer/oligomer, APP, ADAM10, SAPPα, and PreP) showed that LIG reduced Aβ levels in the brain of APP/PS1 mice. Transmission electron microscopy analysis showed that LIG reduced the mitochondria number and increased the mitochondrial length in the hippocampal CA1 area of APP/PS1 mice. A reduced level of Drp1 (fission) and increased levels of Mfn1, Mfn2, and Opa1 (fusion) were found in APP/PS1 mice treated with LIG. An increased ATP level in the brain and increased activities of cytochrome c oxidase (CCO) and succinate dehydrogenase (SDH) in mitochondrion separated from the hippocampus and cortex revealed that LIG alleviated mitochondrial dysfunction. LIG exerts an antioxidation effect via reducing the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) and increasing the activity of Mn-SOD in the brain. Elevated levels of PSD-95, synaptophysin, and synapsin 1 in both the hippocampus and cortex indicated that LIG provided synaptic protection. These findings show that treatment with LIG ameliorates mitochondrial dynamics and morphology issues, improves mitochondrial function, reduces Aβ levels in the brain, restores the synaptic structure, and ameliorates memory deficit in APP/PS1 mice. These results imply that LIG may serve as a potential antidementia drug.

Aging that refers the accumulation of genetic and physiology changes in cells and tissues over a lifetime has been shown a high risk of developing various complex diseases, such as neurodegenerative disease, cardiovascular disease and cancer. Over the past several decades, natural products have been demonstrated as anti-aging interveners via extending lifespan and preventing aging-associated disorders. In this study, we developed an integrated systems pharmacology infrastructure to uncover new indications for aging-associated disorders by natural products. Specifically, we incorporated 411 high-quality aging-associated human genes or human-orthologous genes from mus musculus (MM), saccharomyces cerevisiae (SC), caenorhabditis elegans (CE), and drosophila melanogaster (DM). We constructed a global drug-target network of natural products by integrating both experimental and computationally predicted drug-target interactions (DTI). We further built the statistical network models for identification of new anti-aging indications of natural products through integration of the curated aging-associated genes and drug-target network of natural products. High accuracy was achieved on the network models. We showcased several network-predicted anti-aging indications of four typical natural products (caffeic acid, metformin, myricetin, and resveratrol) with new mechanism-of-actions. In summary, this study offers a powerful systems pharmacology infrastructure to identify natural products for treatment of aging-associated disorders.

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We retrospectively compared the outcomes of children with severe aplastic anemia (SAA) who received immunosuppressive therapy (IST) or who underwent hematopoietic stem cell transplantation (HSCT) from a haploidentical donor (HID), between 2007 and 2016. A total of 52 children with SAA under the age of 17 years were initially treated with IST (n = 24) or haploidentical HSCT (n = 28) as first-line treatment. The estimated 10-year overall survival was 73.4 ± 12.6% and 89.3 ± 5.8% in patients treated with IST or HID-HSCT (P = .806). The failure-free survival was significantly inferior in patients receiving IST than in those undergoing transplantation from an HID (52.6 ± 10.5% vs 89.3 ± 5.8, P = .008). In univariate and multivariate analysis, the choice of first-line immunosuppressive therapy was the only adverse predictor for failure-free survival. At the last follow-up, completely normal blood count was observed in 11 of 20 (55.0%) and 24 of 25 (96.0%) live cases in IST and HID-HSCT cohort (P = .003). These suggest that HSCT from a haploidentical donor could be considered as first-line treatment in children who lack a matched related donor, especially in experienced transplantation centers.

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Background: Pediatric acute myeloid leukemia (AML) with t(8;21) (q22;q22) is classified as a low-risk group. However, relapse is still the main factor affecting survival. We aimed to investigate the effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on reducing recurrence and improving the survival of high-risk pediatric t(8;21) AML based on minimal residual disease (MRD)-guided treatment, and to further explore the prognostic factors to guide risk stratification treatment and identify who will benefit from allo-HSCT. Methods: Overall, 129 newly diagnosed pediatric t(8;21) AML patients were included in this study. Patients were divided into high-risk and low-risk group according to RUNX1-RUNX1T1 transcript levels after 2 cycles of consolidation chemotherapy. High-risk patients were divided into HSCT group and chemotherapy group according to their treatment choices. The characteristics and outcomes of 125 patients were analyzed.