Our previous clinical studies demonstrated the synergistic therapeutic effect induced by co-administering recombinant human erythropoietin (rhEPO) in human umbilical cord blood (hUCB) therapy for children with cerebral palsy. However, the cellular mechanism beyond the beneficial effects in this combination therapy still needs to be elucidated. A hypoxic–ischemic encephalopathy (HIE) model of neonates, representing cerebral palsy, was prepared and randomly divided into five groups (hUCB+rhEPO combination, hUCB, and rhEPO treatments over HIE, HIE control, and sham). Seven days after, hUCB was administered intraperitoneally and the rhEPO injections were started. Neurobehavioral tests showed the best outcome in the combination therapy group, while the hUCB and rhEPO alone treatments also showed better outcomes compared with the control (p < 0.05). Inflammatory cytokines were downregulated by the treatments and attenuated most by the combination therapy (p < 0.05). The hUCB+rhEPO treatment also showed remarkable increase in phosphorylation of Akt and potentiation of anti-apoptotic responses with decreased Bax and increased Bcl-2 (p < 0.05). Pre-treatment of MK-2206, an Akt inhibitor, for the combination therapy depressed the anti-apoptotic effects. In conclusion, these findings suggest that the therapeutic effect of hUCB therapy might be potentiated by co-administration of rhEPO via augmentation of anti-inflammatory and anti-apoptotic responses related to the phosphorylation of Akt.

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by memory impairment in patients. Erythropoietin (EPO) has been reported to stimulate neurogenesis. This study was conducted to determine the regenerative effects of EPO in an AD model and to assess its underlying mechanism. Recombinant human EPO was intraperitoneally administered to AD mice induced by intracerebroventricular Aβ oligomer injection. Behavioral assessments with novel object recognition test and passive avoidance task showed improvement in memory function of the EPO-treated AD mice compared to that of the saline-treated AD mice (p < 0.0001). An in vivo protein assay for the hippocampus and cortex tissue indicated that EPO treatment modulated neurotransmitters, including dopamine, serotonin, and adrenaline. EPO treatment also restored the activity of serotonin receptors, including 5-HT4R, 5-HT7R, and 5-HT1aR (p < 0.01), at mRNA levels. Furthermore, EPO seemed to exert an anti-inflammatory influence by downregulating TLR4 at mRNA and protein levels (p < 0.05). Finally, an immunohistochemical assay revealed increments of Nestin(+) and NeuN(+) neuronal cells in the CA3 region in the EPO-treated AD mice compared to those in the saline-treated AD mice. The conclusion is that EPO administration might be therapeutic for AD by activating the serotonergic pathway, anti-inflammatory action, and neurogenic characteristics.

The amyloid- beta (Aβ) protein is a peptide that plays a central role in the development and progression of Alzheimer's disease, originating from the cleavage of the amyloid precursor protein (APP). The peptide's structural variability is linked to different stages and manifestations of Alzheimer's pathology, making it a critical focus for understanding the disease. Current therapeutic strategies primarily involve pharmacological interventions, but they have met with limited success in altering the course of the disease. Our research introduces an innovative approach to address this challenge by employing electromagnetic waves, specifically at a frequency of 900 MHz We performed comprehensive electromagnetic simulations to explore the effects of this frequency on Aβ structures, aiming to offer an alternative non-invasive treatment avenue. Following these electromagnetic simulations, molecular dynamics (MD) simulations were carried out using the Large Scale Atomic/Molecular Massively Parallel Simulation (LAMMPS) software to further investigate the peptide’s response at the atomic and molecular level. These simulations provided insights into the structural dynamics of Aβ under electromagnetic influence, enabling a deeper understanding of the peptide’s behavior. To substantiate the findings from our simulations and the theoretical framework, we conducted a Thioflavin T (ThT) assay and western blot analysis on in vitro Aβ fibril samples which are treated with electromagnetic (EM) wave exposure using a TEM cell device. After 3 hours of EM wave exposure, a noticeable decrease in Aβ fibrils was observed. This experimental validation was essential in confirming the simulation results and reinforcing the theoretical basis of our approach. Together, simulations and experimental evidence provide a strong foundation for exploring electromagnetic-based treatments as a potential therapeutic intervention for Alzheimer’s disease.

Simulation-based functional verification is characterized by two inherently conflicting targets: the signal visibility and simulation performance. Achieving a proper trade-off between these two targets is of paramount importance. Even though HDL simulators are the most widely used verification platform at the RTL and gate level, their major drawback is the low performance in verifying complex SOCs, especially when the high visibility over the design under verification is required. This paper presents a new, fast simulation method as an effective way to achieve both high simulation speed and full signal visibility. It is based on an original two-pass simulation approach. During the 1 ^st pass, with the simulation running at full speed, a set of design states is saved periodically at predetermined checkpoints. During the 2 ^nd pass, another simulation is performed, using any of saved checkpoints and providing 100% signal visibility for debugging. Our method differs from the traditional simulation snapshot approach in the amount and the way the design state is saved. Experimental results show significant speed-up compared to existing traditional simulation methods while maintaining 100% visibility.