This study was designed to assess the changes in nonlinear properties of heart rate (HR) variability (HRV) during the menstrual cycle by means of complexity measures, including sample entropy (SampEn) and correlation dimension (CD), and explore probable physiological interpretations for them. In 16 healthy women (mean age: 23.8 +/- 2.7 yr), complexity measures along with the spectral components of HRV (sympathovagal markers) were analyzed over 1,500 R-R intervals recorded during both the follicular phase (day 11.9 +/- 1.4) and the luteal phase (day 22.0 +/- 1.4) of each woman's menstrual cycle. Simultaneously, serum ovarian hormone (estradiol-17 and progesterone) and thyroid-related hormone [free triiodothyronine, free thyroxine (T(4)), and thyroid-stimulating hormone] concentrations were measured. With regard to HRV measures, SampEn, CD, and high-frequency (HF) components decreased from the follicular phase to the luteal phase, whereas normalized low-frequency (LF) components and the LF-to-HF ratio as well as resting HR increased. In regard to hormone levels, whereas progesterone was increased, the other hormone concentrations were unchanged. Furthermore, across the menstrual cycle, both SampEn and CD were well correlated with the spectral indexes and free T(4) concentrations, and SampEn also showed significant correlations with the ratio of estradiol-17 to progesterone concentrations. These results suggest that the nonlinear properties in HRV are altered during the regular menstrual cycle and that the autonomic nervous system, ovarian hormone balance, and free T(4) may be involved in nonlinear HR control in healthy women. All of these factors may enrich the physiological meanings of complexity measures.

Glioblastoma (GBM) is the most common type of malignant tumor of the central nervous system. The prognosis of patients with GBM is very poor, with a survival time of ~15 months. GBM is highly heterogeneous and highly aggressive. Surgical removal of intracranial tumors does provide a good advantage for patients as there is a high rate of recurrence. The understanding of this type of cancer needs to be strengthened, and the aim of the present study was to identify gene signatures present in GBM and uncover their potential mechanisms. The gene expression profiles of GSE15824 and GSE51062 were downloaded from the Gene Expression Omnibus database. Normalization of the data from primary GBM samples and normal samples in the two databases was conducted using R software. Then, joint analysis of the data was performed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed using Cytoscape software. Identification of prognostic biomarkers was conducted using UALCAN. In total, 9,341 DEGs were identified in the GBM samples, including 9,175 upregulated genes and 166 downregulated genes. The top 1,000 upregulated DEGs and all of the downregulated DEGs were selected for GO, KEGG and prognostic biomarker analyses. The GO results showed that the upregulated DEGs were significantly enriched in biological processes (BP), including immune response, cell division and cell proliferation, and the downregulated DEGs were also significantly enriched in BP, including cell growth, intracellular signal transduction and signal transduction by protein phosphorylation. KEGG pathway analysis showed that the upregulated DEGs were enriched in circadian entrainment, cytokine-cytokine receptor interaction and maturity onset diabetes of the young, while the downregulated DEGs were enriched in the TGF-β signaling pathway, MAPK signaling pathway and pathways in cancer. All of the downregulated genes and the top 1,000 upregulated genes were selected to establish the PPI network, and the sub-networks revealed that these genes were involved in significant pathways, including olfactory transduction, neuroactive ligand-receptor interaction and viral carcinogenesis. In total, seven genes were identified as good prognostic biomarkers. In conclusion, the identified DEGs and hub genes contribute to the understanding of the molecular mechanisms underlying the development of GBM and they may be used as diagnostic and prognostic biomarkers and molecular targets for the treatment of patients with GBM in the future.

Extracellular aggregation of the β-amyloid (Aβ) peptide into toxic multimers in the brain is a prominent event occurring in the pathogenesis of Alzheimer’s disease (AD), and a large amount of Aβ in the blood is derived from platelets. Thus, we speculated that platelets may play an important role in the process of AD. We first investigated the changes in platelet Aβ secretion with age. Then, we injected platelets from aged amyloid precursor protein APP/PS1 mice into young C57 mice and assessed their memory capacity along with their brain and peripheral blood Aβ expression levels. The Aβ content in mouse platelets increased with age. Exogenously aged APP/PS1 platelets changed the permeability of the blood-brain barrier in vitro , accelerating Aβ deposition in the brain and increasing the Aβ content in peripheral blood, leading to learning and memory deficits in the recipient mice. Subsequently, aspirin was administered to mice as an inhibitor of platelet activation, which effectively alleviated these toxic processes. Finally, we chose an in vitro blood-brain barrier model to explore the possible cytotoxicity of these platelets.

The aging brain with mitochondrial dysfunction and a reduced adenosine 5’-triphosphate (ATP) has been implicated in the onset and progression of β-Amyloid (Aβ)-induced neuronal toxicity in AD. To unravel the function of ATP and the underlying mechanisms on AD development, APP/PS1 double transgenic mice and wild-type (WT) C57 mice at 6 and 10 months of age were studied. We demonstrated a decreased ATP release in the hippocampus and platelet of APP/PS1 mice, comparing to C57 mice at a relatively early age. Levels of Aβ were raised in both hippocampus and platelet of APP/PS1 mice, accompanied by a decrease of α-secretase activity and an increase of β-secretase activity. Moreover, our results presented an age-dependent rise in mitochondrial vulnerability to oxidation in APP/PS1 mice. In addition, we found decreased pSer473-Akt levels, increased GSK3β activity by inhibiting phosphorylation at Ser9 in aged APP/PS1 mice and these dysfunctions probably due to down-regulation of Bcl-2 and up-regulation of cleaved caspase-3. Therefore, we demonstrate that PI3K/Akt/GSK3β signaling pathway could be involved in Aβ-associated mitochondrial dysfunction of APP/PS1 mice and APP abnormal metabolism in platelet might provide potential biomarkers for early diagnosis of AD.

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