Glucose attenuates the long-term adverse neurodevelopment effect of neonate pain stimulus via CRF/GR in rats.

BACKGROUND: Neonates undergo numerous painful procedures throughout their hospitalization. Repeated procedural pain may cause adverse long-term effects. Glucose as a non-pharmacological analgesia, is used for neonate pain management. In this study, potential mechanism of attenuate pain induced by glucose in neurodevelopment effect of neonate pain stimulus was investigated. METHODS: Neonatal rats to perform a repetitive injury model and glucose intervention model in the postnatal day 0-7(P0-7). Pain thresholds were measured by von Frey test weekly. The puberty behavioral outcome, tissue loss and protein expression in hippocampus were analyzed. RESULTS: Oral administration of glucose after repeated pain stimulation can maintain the hippocampal structure in, and reduce the expressions of corticotropin releasing factor (CFR) and glucocorticoid receptor (GR), therefore, resulted in long-term threshold of pain and cognitive improvement. CONCLUSION: Exposure to neonatal repeated procedural pain causes persistent mechanical hypersensitivity and the dysfunction of spatial memory retention at puberty. In addition, glucose can relieve these adverse effects, possibly via decreasing CRF/GR levels to change the hypothalamus-pituitary-adrenal (HPA) axis.

Long-chain acyl-CoA synthetase-4 regulates endometrial decidualization through a fatty acid ß-oxidation pathway rather than lipid droplet accumulation.

OBJECTIVE: Lipid metabolism plays an important role in early pregnancy, but its effects on decidualization are poorly understood. Fatty acids (FAs) must be esterified by fatty acyl-CoA synthetases to form biologically active acyl-CoA in order to enter the anabolic and/or catabolic pathway. Long-chain acyl-CoA synthetase 4 (ACSL4) is associated with female reproduction. However, whether it is involved in decidualization is unknown. METHODS: The expression of ACSL4 in human and mouse endometrium was detected by immunohistochemistry. ACSL4 levels were regulated by the overexpression of ACSL4 plasmid or ACSL4 siRNA, and the effects of ACSL4 on decidualization markers and morphology of endometrial stromal cells (ESCs) were clarified. A pregnant mouse model was established to determine the effect of ACSL4 on the implantation efficiency of mouse embryos. Modulation of ACSL4 detects lipid anabolism and catabolism. RESULTS: Through examining the expression level of ACSL4 in human endometrial tissues during proliferative and secretory phases, we found that ACSL4 was highly expressed during the secretory phase. Knockdown of ACSL4 suppressed decidualization and inhibited the mesenchymal-to-epithelial transition induced by MPA and db-cAMP in ESCs. Further, the knockdown of ACSL4 reduced the efficiency of embryo implantation in pregnant mice. Downregulation of ACSL4 inhibited FA ß-oxidation and lipid droplet accumulation during decidualization. Interestingly, pharmacological and genetic inhibition of lipid droplet synthesis did not affect FA ß-oxidation and decidualization, while the pharmacological and genetic inhibition of FA ß-oxidation increased lipid droplet accumulation and inhibited decidualization. In addition, inhibition of ß-oxidation was found to attenuate the promotion of decidualization by the upregulation of ACSL4. The decidualization damage caused by ACSL4 knockdown could be reversed by activating ß-oxidation. CONCLUSIONS: Our findings suggest that ACSL4 promotes endometrial decidualization by activating the ß-oxidation pathway. This study provides interesting insights into our understanding of the mechanisms regulating lipid metabolism during decidualization.

Shape characterization and discrimination of single nanoparticles using solid-state nanopores.

Resistive pulse sensing with nanopores is expected to enable identification and analysis of nanoscale objects in ionic solutions. However, there is currently no remarkable method to characterize the three-dimensional shape of charged biomolecules or nanoparticles with low-cost and high-throughput. Here we demonstrate the sensing capability of solid-state nanopores for shape characterization of single nanoparticles by monitoring the ionic current blockades during their electrophoretic translocation through nanopores. By using nanopores that are a bit larger than the particles, shape characterization of both spherical and cubic silver nanoparticles is successfully realized due to their rapid rotation with respect to the pore axis, which is further validated by our all-atom molecular dynamics simulations. The single-molecule approach based on nanopores will allow people to measure the dimension and to characterize the shape of single nanoparticles or proteins simultaneously in real time, which is significant for its potential application in investigation of structural biology and proteomics in the near future.

Construction of H4x K2x Sn2-x S4+x /TiO2 nanocomposites with enhanced visible light-driven photocatalytic performance.

In this paper, a new photocatalyst with TiO2 nanospheres decorated on ultrathin layered thiostannate H4x K2x Sn2-x S4+x (X = 0.5-0.6, HKTS) nanosheets was successfully synthesized by a facile solvothermal method combined with the hydrolysis of tetrabutyl titanate and it was denoted as HKTS/TiO2. By adjusting the content of tetrabutyl titanate, composites with different Sn/Ti molar ratios were prepared. The composites were applied for RhB degradation under visible light irradiation, and the optimum proportion of HKTS/TiO2 was obtained. The results of X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy and scanning electron microscopy confirmed that TiO2 was successfully decorated on HKTS nanosheets. The combination of TiO2 and HKTS extended the absorption wavelength of TiO2 from UV to visible light range, and the separation efficiency of photoexcited electron-hole pairs was also enhanced. The photocatalytic degradation rate of RhB over HKTS/TiO2-1.0 was almost 97.9% after 60 min illumination, which was higher than those of HKTS and pure TiO2. The photocatalyst exhibited excellent reusability and stability as the degradation rate of RhB was 95.7% even after three cycles. The photocatalytic mechanism experiment indicated that ·O2 - and h+ played a dominant role in the photocatalytic process. All these results indicate that the newly fabricated HKTS/TiO2 composites provide a high-performance photocatalyst for waste water treatment, and the application of thiostannate can be extended to the field of photocatalytic materials.

Emerging Roles of 5-Lipoxygenase Phosphorylation in Inflammation and Cell Death.

5-Lipoxygenase (ALOX5) is an iron-containing and nonheme dioxygenase that catalyzes the peroxidation of polyunsaturated fatty acids such as arachidonic acid. ALOX5 is the rate-limiting enzyme for the biosynthesis of leukotrienes, a family of proinflammatory lipid mediators derived from arachidonic acid. ALOX5 also make great contributions to mediating lipid peroxidation. In recent years, it has been discovered that ALOX5 plays a central role in cell death including apoptosis, pyroptosis, and ferroptosis, a newly discovered type of cell death. According to the previous studies, ALOX5 can regulate cell death in two ways: one is inflammation and the other is lipid peroxidation. Meanwhile, it has been shown that ALOX5 activity is regulated by several factors including protein phosphorylation, ALOX5-interactng protein, redox state, and metal ions such as iron and calcium. In this review, we aim to summarize the knowledge on the emerging roles of ALOX5 protein phosphorylation in the regulation of cell death and inflammation in order to explore a potential target for human diseases.

Baicalein Exerts Neuroprotective Effects in FeCl3-Induced Posttraumatic Epileptic Seizures via Suppressing Ferroptosis.

Posttraumatic epilepsy (PTE) is a prevalent type of acquired epilepsy secondary to traumatic brain injury, and is characterized by repeated seizures. Traditional antiepileptic drugs have minimal response in preventing posttraumatic epileptic seizures. It is essential for the development of new therapeutic strategy. Our previous work disclosed a potent neuroprotective role of baicalein, a flavonoid extracted from Scutellaria baicalensis Georgi, against inherited epilepsy in rats. Whether baicalein has protective potential in posttraumatic epileptic seizures and the possible molecular mechanism remain elusive. Additionally, the brain is vulnerable to lipid peroxidation-induced damage due to high consumption of oxygen and abundant polyunsaturated fatty acids in neuronal membranes. Our present investigation aimed to elucidate whether baicalein exerts neuroprotective effects on posttraumatic epileptic seizures by inhibiting ferroptosis, a newly discovered lipid peroxidation-dependent cell death modality. We found that baicalein significantly reduced seizure score, number of seizures, and average seizure duration in an iron chloride (FeCl3)-induced PTE mouse model. The neuroprotective effect of baicalein was also validated in a ferric ammonium citrate (FAC)-induced HT22 hippocampal neuron damage model. Moreover, in vitro, baicalein could remarkably decrease ferroptotic indices (lipid reactive oxygen species, 4-hydroxynonenal, and prostaglandin endoperoxide synthase 2) and inhibit the expression of 12/15-lipoxygenase (12/15-LOX) in an iron-induced HT22 cell damage model. These findings were also validated in a mouse PTE model. It was concluded that baicalein exerted neuroprotective effects against posttraumatic epileptic seizures via suppressing ferroptosis and 12/15-LOX was likely to be involved in baicalein's neuroprotection.

Collagen I enhances the efficiency and anti-tumor activity of dendritic-tumor fusion cells.

Low fusion efficiency and nominal activity of fusion cells (FCs) restrict the clinical application of dendritic cell (DC)/tumor fusion cells. Collagen I (Col I) is an interstitial collagen with a closely-knit structure used to repair damaged cell membranes. This study evaluated whether Col I could improve the fusion efficiency of polyethylene glycol (PEG)-induction and enhance the immunogenicity of fusion vaccine. DC/B16 melanoma and controlled DC/H22 hepatoma cell fusions were induced by PEG with or without Col I. Col I/PEG treatment increased the levels of DC surface molecules and the secretion of lactate, pro- and anti-inflammatory cytokines in fusion cells. Col I/PEG-treated FCs enhanced T-cell proliferation and cytotoxic T lymphocyte activity. The Col I-prepared fusion vaccine obviously suppressed tumor growth and prolonged mice survival time. Thus Col I treatment could significantly improve the efficiency of PEG-induced DC/tumor fusion and enhance the anticancer activity of the fusion vaccine. This novel fusion strategy might promote the clinical application of DC/tumor fusion immunotherapy.