Zinc has been considered as a vital constituent of proteins, including enzymes. Mobile reactive zinc (Zn2+) is the key form of zinc involved in signal transductions, which are mainly driven by its binding to proteins or the release of zinc from proteins, possibly via a redox switch. There has been growing evidence of zinc's critical role in cell signaling, due to its flexible coordination geometry and rapid shifts in protein conformation to perform biological reactions. The importance and complexity of Zn2+ activity has been presumed to parallel the degree of calcium's participation in cellular processes. Whole body and cellular Zn2+ levels are largely regulated by metallothioneins (MTs), Zn2+ importers (ZIPs), and Zn2+ transporters (ZnTs). Numerous proteins involved in signaling pathways, mitochondrial metabolism, and ion channels that play a pivotal role in controlling cardiac contractility are common targets of Zn2+. However, these regulatory actions of Zn2+ are not limited to the function of the heart, but also extend to numerous other organ systems, such as the central nervous system, immune system, cardiovascular tissue, and secretory glands, such as the pancreas, prostate, and mammary glands. In this review, the regulation of cellular Zn2+ levels, Zn2+-mediated signal transduction, impacts of Zn2+ on ion channels and mitochondrial metabolism, and finally, the implications of Zn2+ in health and disease development were outlined to help widen the current understanding of the versatile and complex roles of Zn2+.

Amyloid β (Aβ) deposition is a hallmark of Alzheimer’s disease (AD). Vascular modifications, including altered brain endothelial cell function and structural viability of the blood-brain barrier due to vascular pulsatility, are implicated in AD pathology. Pulsatility of phenomena in the cerebral vasculature are often not considered in in vitro models of the blood-brain barrier. We demonstrate, for the first time, that pulsatile stretch of brain vascular endothelial cells modulates amyloid precursor protein (APP) expression and the APP processing enzyme, β-secretase 1, eventuating increased-Aβ generation and secretion. Concurrent modulation of intercellular adhesion molecule 1 and endothelial nitric oxide synthase (eNOS) signaling (expression and phosphorylation of eNOS) in response to pulsatile stretch indicates parallel activation of endothelial inflammatory pathways. These findings mechanistically support vascular pulsatility contributing towards cerebral Aβ levels.

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Background and PurposeDravet syndrome is a rare and severe type of epilepsy in infants. The heterogeneity in the overall intellectual disability that these patients suffer from has been attributed to differences in genetic background and epilepsy severity.MethodsEighteen Vietnamese children diagnosed with Dravet syndrome were included in this study. SCN1A variants were screened by direct sequencing and multiplex ligation-dependent probe amplification. Adaptive functioning was assessed in all patients using the Vietnamese version of the Vineland Adaptive Behavior Scales, and the results were analyzed relative to the SCN1A variants and epilepsy severity.ResultsWe identified 13 pathogenic or likely pathogenic variants, including 6 that have not been reported previously. We found no correlations between the presence or type of SCN1A variants and the level of adaptive functioning impairment or severity of epilepsy. Only two of nine patients aged at least 5 years had an adaptive functioning score higher than 50. Both of these patients had a low frequency of convulsive seizures and no history of status epilepticus or prolonged seizures. The remaining seven had very low adaptive functioning scores (39 or less) despite the variability in the severity of their epilepsy confirming the involvement of factors other than the severity of epilepsy in determining the developmental outcome.ConclusionsOur study expands the spectrum of known SCN1A variants and confirms the current understanding of the role of the genetic background and epilepsy severity in determining the developmental outcome of Dravet syndrome patients.

This study was conducted to investigate the quality characteristics and changes in isoflavone content of Cheonggukjang with added Chaga mushroom by secondary fermentation at 40℃ for 48 h with or without a starter, Lactobacillus acidophilus KCTC 3925. Cheonggukjang samples were divided into three groups: Control (unsterilized Cheonggukjang fermented without a starter), NS (unsterilized Cheonggukjang inoculated with L. acidophilus KCTC 3925), and YS (heat-sterilized Cheonggukjang inoculated with L. acidophilus KCTC 3925). The approximate composition of the three types of

A phytochemical application of leaves from Ficus erecta var. sieboldii (Miq.) King has not been widely investigated. We determined an anti-inflammatory effect of F. erecta extracts on lipopolysaccharide (LPS)-mediated production through modulation of several pro-inflammatory mediators and prostaglandin E2 (PGE 2). Among the F. erecta extracts, the CH 2 Cl 2 fraction (CFE) most effectively suppressed the LPS-mediated production of nitric oxide (NO) in Raw264.7 cells. As determined by immunoblotting and PCR, CFE was shown to have an inhibitory effect on LPS-induced mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, CFE showed significant inhibitory effects on LPS-mediated production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and PGE 2 (P<0.05), demonstrating its effects on inflammation. The main active compounds that suppressed PGE 2 production were syringaresinol (C1) and 6,7-furano-5-methoxy hydrocoumaric acid (C2). In conclusion, CFE showed an inhibitory effect on LPS-mediated inflammatory responses by suppressing iNOS, COX-2, TNF-α, IL-1β, and IL-6 production. The compounds C1 and C2 showed strong inhibitory effects on LPS-mediated production of PGE 2 and may be applicable as starter compounds for developing anti-inflammatory and anti-nociceptive drugs.

It has been shown that glial cells and macrophages have many both similar and different characteristics including signalings responsible for production of NO. In the present study, we examined the effect of fucoidan on NO and iNOS production induced by TNF‐α and IFN‐γ, comparing between Raw264.7 and C6 cells. Our data shows that fucoidan affects only IFN‐γ‐induced iNOS but not TNF‐α‐induced iNOS in both cells. Elucidating mechanisms underlying effect of fucoidan on IFN‐γ signaling, we found that fucoidan inhibited IFN‐γ‐induced iNOS expression in C6 cells via inhibition of JAK/STAT and p38 activation. In contrast, in Raw264.7, fucoidan increased IFN‐γ‐induced iNOS via increase TNF‐α production which is negatively regulated by p38. We also found that the effect of fucoidan on Raw264.7 was not mediated by SR‐A1, a well‐known receptor of fucoidan, suggesting the involvement of other receptors. Our data, therefore, show the marked difference between glial cells and macrophages in response to fucoidan which should be considered in clinical using of fucoidan (This work was supported by grant No. RTI05‐01‐02 from the Regional Technology Innovation Program of the Ministry of Konwledge Economy(MKE)).

The purpose of this study was to investigate the effect of calcium supplementation combined with fucoidan and chitooligisaccaride (COS) on bone mineral density (BMD) in ovariectomized rats. A total of 48 female Wistar rats (six weeks) were used this study and 40 rats were ovariectomized (OVX), and the rest of rats were sham‐operated. The Sham and one OVX group were fed standard diet, and the remaining OVX groups received either a fucoidan (0.05%) supplemented diet, a COS (0.5%) supplemented diet, a seaweed Ca supplemented diet (Ca 1.5%), or a fucoidan, COS and seaweed Ca supplemented diet for 12 weeks. There was significant difference in final weight, therefore, we analyzed the BMD data as dividing by the final weight. BMDs of lumbar spine, femur and tibia were significantly lower in ovariectomized rat compared to the Sham group. Ca supplementation increased the BMDs of lumbar spine and femur, however, fucoidan or COS alone supplementation didn't increase the BMD of OVX rats. While, complex supplementation of fucoidan, COS and Ca more effectively improved the BMDs of measured all three sites than Ca alone supplementation in OVX rats. To summarize the results, Ca supplementation combined with fucoidan and chitooligosaccaride may have a greater effect improving the BMD compared with Ca alone supplementation in ovariectomized rats.