Cinnamaldehyde protects cardiomyocytes from oxygen-glucose deprivation/reoxygenation-induced lipid peroxidation and DNA damage via activating the Nrf2 pathway.

Rapid restoration of perfusion in ischemic myocardium is the most direct and effective treatment for coronary heart disease but may cause myocardial ischemia/reperfusion injury (MIRI). Cinnamaldehyde (CA, C9H8O), a key component in the well-known Chinese medicine cinnamomum cassia, has cardioprotective effects against MIRI. This study aimed to observe the therapeutic effect of CA on MIRI and to elucidate its potential mechanism. H9C2 rat cardiomyocytes were pretreated with CA solution at 0, 10, and 100 µM, respectively and subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Then the cell viability, the NF-κB and caspase3 gene levels, the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, superoxide dismutase (SOD) level, reactive oxygen species (ROS) generation, 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) were detected. The severity of DNA damage was assessed by tail moment (TM) values using alkaline comet assay. Besides, the DNA damage-related proteins and the key proteins of the Nrf2 pathway were detected by western blot. CA treatment increased the cell viability, GHS/GSSG ratio, SOD level, PARP1, Nrf2, PPAR-γ, and HO-1 protein levels of H9C2 cardiomyocytes, while reducing NF-κB, caspase3, ROS level, 4-HNE and MDA content, γ-H2AX protein level, and TM values. Inhibition of the Nrf2 pathway reversed the effect of CA on cell viability and apoptosis of OGD/R induced H9C2 cardiomyocytes. Besides, 100 µM CA was more effective than 10 µM CA. In the OGD/R-induced H9C2 cardiomyocyte model, CA can protect cardiomyocytes from MIRI by attenuating lipid peroxidation and repairing DNA damage. The mechanism may be related to the activation of the Nrf2 pathway.

Differential activation of the medial temporal lobe during item and associative memory across time.

Studies have shown that the hippocampus plays a crucial role in associative memory. One central issue is whether the involvement of the hippocampus in associative memory remains stable or declines with the passage of time. In the majority of studies, memory performance declines with delay, confounding attempts at interpreting differences in hippocampal activation over time. To address this issue, we tried to equate behavioral performance as much as possible across time for memory of items and associations separately. After encoding words and word pairs, participants were tested for item and associative memories at four time intervals: 20-min, 1-day, 1-week, and 1-month. The results revealed that MTL activation differed over time for associative and item memories. For associative memory, the activation of the anterior hippocampus decreased from 20-min to 1-day then remained stable, whereas in the posterior hippocampus, the activation was comparable for different time intervals when old pairs were correctly retrieved. The hippocampal activation also remained stable when recombined pairs were correctly rejected. As this condition controls for familiarity of the individual items, correct performance depends only on associative memory. For item memory, hippocampal activation declined progressively from 20-min to 1-week and remained stable afterwards. By contrast, the activation in the perirhinal/entorhinal cortex increased over time irrespective of item and associative memories. Drawing on Tulving's distinction between recollection and familiarity, we interpret this pattern of results in accordance with Trace Transformation Theory, which states that as memories are transformed with time and experience, the neural structures mediating item and associative memories will vary according to the underlying representations to which the memories have been transformed.

Impairment of regulatory T cells in patients with neonatal necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a life-threatening condition that can occur in about 7% of pre-term infants, and approximately 20% to 30% of the cases will end in death. An overactive immune response is thought to be a primary instigator of many symptoms during NEC. Hence, we hypothesized that NEC patients might present impairment in regulatory T (Treg) cells that limited their capacity to contain the excessive inflammation-induced damage. To investigate this, peripheral blood mononuclear cells were collected from NEC and non-NEC infants with matching age and weight. Treg cells, identified as CD3+CD4+CD25+/hiFoxp3+ T cells, were present at significantly lower frequency in NEC infants than in non-NEC infants. We also observed that the frequency of IL­17+ CD4+ T cells was significantly higher in NEC infants, while the frequencies of IL­10+ and TGF­ß+ CD4+ T cells were significantly lower in NEC infants. The CD4+CD25+/hi Treg cells from NEC infants were capable of suppressing CD4+CD25- T conventional cell proliferation, but with significantly reduced potency than the CD4+CD25+/hi Treg cells from non-NEC infants. In addition, the CD4+CD25+/hi Treg cells from non-NEC infants, but not those from NEC infants, were capable of suppressing IL­17 expression. Furthermore, the CD4+CD25+/hi Treg cells from NEC infants displayed reduced expression of CTLA­4, LAG­3, and Helios, compared to those from non-NEC infants. Overall, these results demonstrated that Treg cells from NEC infants displayed a multitude of functional impairments, and suggested that Treg cells might serve as a treatment target in NEC.

Monocyte activation and inflammation can exacerbate Treg/Th17 imbalance in infants with neonatal necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a potentially fatal disease that develops in the intestinal tract of newborn infants. An overactive immune system in the intestinal tract of NEC patients not only propagates inflammation and mediates tissue damage, but may also radiate the disease systemically and impose injury to distant organs. We previously identified impairment in the Treg compartment in NEC patients. Here, we hypothesized that monocytes, which could promote iTreg differentiation both in vitro and in vivo, were dysregulated in NEC infants. In age-, sex-, and weight-matched NEC infants and healthy control infants, the monocytes from PBMCs were investigated. Monocytes from NEC infants presented significantly higher TLR4 expression. With or without LPS stimulation, monocytes from NEC infants presented elevated TNF-α and IL-6 expression, together with reduced expression of TGF-ß. When incubated with autologous CD4+ T cells, monocytes from NEC infants preferentially promoted the differentiation of RORγt-expressing Th17 cells, but not Foxp3-expressing Treg cells. However, using exogenous TGF-ß and IL-10, the development of Foxp3 expression could be significantly elevated. Together, these results demonstrate that monocytes in NEC patients displayed a proinflammatory profile that might contribute to the production of proinflammatory cytokines and the suppression of Treg cells.

Effects of learning experience on forgetting rates of item and associative memories.

Are associative memories forgotten more quickly than item memories, and does the level of original learning differentially influence forgetting rates? In this study, we addressed these questions by having participants learn single words and word pairs once (Experiment 1), three times (Experiment 2), and six times (Experiment 3) in a massed learning (ML) or a distributed learning (DL) mode. Then they were tested for item and associative recognition separately after four retention intervals: 10 min, 1 d, 1 wk, and 1 mo. The contribution of recollection and familiarity processes were assessed by participants' remember/know judgments. The results showed that for both item and associative memories, across different degrees of learning, recollection decreased significantly and was the main source of forgetting over time, whereas familiarity remained relatively stable over time. Learning multiple times led to slower forgetting at shorter intervals, depending on recollection and familiarity processes. Compared with massed learning, distributed learning (six times) especially benefited associative memory by increasing recollection, leading to slower forgetting at longer intervals. This study highlighted the importance of process contribution and learning experiences in modulating the forgetting rates of item and associative memories. We interpret these results within the framework of a dual factor representational model of forgetting (as noted in a previous study) in which recollection is more prone to decay over time than familiarity.

Effects of unconscious processing on implicit memory for fearful faces.

Emotional stimuli can be processed even when participants perceive them without conscious awareness, but the extent to which unconsciously processed emotional stimuli influence implicit memory after short and long delays is not fully understood. We addressed this issue by measuring a subliminal affective priming effect in Experiment 1 and a long-term priming effect in Experiment 2. In Experiment 1, a flashed fearful or neutral face masked by a scrambled face was presented three times, then a target face (either fearful or neutral) was presented and participants were asked to make a fearful/neutral judgment. We found that, relative to a neutral prime face (neutral-fear face), a fearful prime face speeded up participants' reaction to a fearful target (fear-fear face), when they were not aware of the masked prime face. But this response pattern did not apply to the neutral target. In Experiment 2, participants were first presented with a masked faces six times during encoding. Three minutes later, they were asked to make a fearful/neutral judgment for the same face with congruent expression, the same face with incongruent expression or a new face. Participants showed a significant priming effect for the fearful faces but not for the neutral faces, regardless of their awareness of the masked faces during encoding. These results provided evidence that unconsciously processed stimuli could enhance emotional memory after both short and long delays. It indicates that emotion can enhance memory processing whether the stimuli are encoded consciously or unconsciously.