CaMKII and CaV3.2 T-type calcium channel mediate Connexin-43-dependent inflammation by activating astrocytes in vincristine-induced neuropathic pain.

Vincristine (VCR), an alkaloid isolated from vinca, is a commonly used chemotherapeutic drug. However, VCR therapy can lead to dose-dependent peripheral neurotoxicity, mainly manifesting as neuropathic pain, which is one of the dominant reasons for limiting its utility. Experimentally, we discovered that VCR-induced neuropathic pain (VINP) was accompanied by astrocyte activation; the upregulation of phospho-CaMKII (p-CaMKII), CaV3.2, and Connexin-43 (Cx43) expression; and the production and release of inflammatory cytokines and chemokines in the spinal cord. Similar situations were also observed in astrocyte cultures. Interestingly, these alterations were all reversed by intrathecal injection of KN-93 (a CaMKII inhibitor) or L-Ascorbic acid (a CaV3.2 inhibitor). In addition, KN-93 and L-Ascorbic acid inhibited the increase in [Ca2+]i associated with astrocyte activation. We also verified that knocking down or inhibiting Cx43 level via intrathecal injection of Cx43 siRNA or Gap27 (a Cx43 mimetic peptide) relieved pain hypersensitivity and reduced the release of inflammatory factors; however, they did not affect astrocyte activation or p-CaMKII and CaV3.2 expression. Besides, the overexpression of Cx43 through the transfection of the Cx43 plasmid did not affect p-CaMKII and CaV3.2 expressions in vitro. Therefore, CaMKII and CaV3.2 may activate astrocytes by increasing [Ca2+]i, thereby mediating Cx43-dependent inflammation in VINP. Moreover, we demonstrated that the CaMKII signalling pathway was involved in VCR-induced inflammation, apoptosis, and mitochondrial damage. Collectively, our findings show a novel mechanism by which CaMKII and CaV3.2 mediate Cx43-dependent inflammation by activating astrocytes in neuropathic pain induced by VCR.

Carbon Dots Derived from the Maillard Reaction for pH Sensors and Cr (VI) Detection.

The Maillard reaction involves a series of complex reactions; fluorescent compounds have been considered as vital intermediate products of the reaction. In this article, carbon dots (CDs) based on the Maillard reaction (MR-CDs) were prepared with L-tryptophan and D-glucose, and they had excellent photoluminescence stability. MR-CDs showed stable pH-dependence behavior and exhibited an excellent linear response to pH in the range of 4.0-7.5 and 7.5-13.0, respectively. Under the masking effect of sodium fluoride for Fe(III), MR-CDs showed excellent selectivity and sensitivity for Cr (VI). The linear range of Cr(VI) was 0.2-50 µM and the limit of detection was 20 nM. (S/N ≥ 3). Furthermore, MR-CDs were used to detect Cr(VI) in tap water samples. The recoveries were between 95.8% and 98.94%, and RSDs were less than 3.17%.

Acid sphingomyelinase downregulation alleviates vascular endothelial leptin resistance in rats.

Leptin resistance in endothelial cells leads to vascular endothelial dysfunction, which is the beginning and crucial link of atherosclerosis. However, the mechanism of leptin resistance remains obscure. Acid sphingomyelinase (ASM) catalyzes the hydrolysis of sphingomyelin to produce ceramide, which plays an important role in the progression of metabolic and cardiovascular diseases. In this study, we investigated whether ASM could regulate leptin resistance in vascular endothelial cells. We induced endothelial leptin resistance in rat aortic endothelial cells through treatment with palmitic acid (0.3 mM) or knockdown of leptin receptor (Ob-Rb), which resulted in the increase of suppressor of cytokine signaling 3 expression, the decrease of Ob-Rb expression, and signal transducer and activator of transcription 3 (STAT3) phosphorylation at Tyr705. We found that these indicators of leptin resistance were reversed by knockdown of ASM or by the selective ASM inhibitors amitriptyline (AMI) and imipramine (IMI). Supplementation of ceramide inhibited Ob-Rb expression and STAT3 phosphorylation by inhibiting extracellular signal-regulated kinase 1/2 activation. Furthermore, we found that knockdown of ASM enhanced endothelial nitric oxide (NO) synthase activity and NO production, as well as the Akt phosphorylation at ser473, which was regulated by STAT3. High-fat diet (HFD) feeding-induced leptin resistance in rats in vivo; administration of AMI and IMI (10 mg· kg-1 per day, intraperitoneally, for 2 weeks) increased the release of endothelial NO to relieve the vasodilatory response and improved the endothelial leptin resistance in the aorta of HFD-fed rats. These results suggest that ASM downregulation reverses endothelial leptin resistance, and consequently improves vascular endothelial dysfunction. This study highlighted ASM as a potential therapeutic target for endothelial leptin resistance.

Structure and Functional Properties of Antioxidant Nanoemulsions Prepared with Tea Polyphenols and Soybean Protein Isolate.

In this study, tea polyphenols (TP) was added to a soy protein isolate (SPI) to prepare nanoemulsions by ultra-high pressure homogenization (UHPH). The nanoemulsions were characterized by a confocal laser scanning electron microscopy, infrared spectroscopy, dynamic rheometer and size-potential analyzer. The effects of TP on the hydrophobicity, emulsifiability, particle size, potential and antioxidant capacity of the prepared nanoemulsions were investigated. The properties of the nanoemulsions with different concentrations of TP were analyzed. The results indicated that ultra-high pressure homogenization treatment contributed to the formation of the SPI-TP complex that showed higher antioxidant activity. The nanoemulsions with good emulsifying properties and high DPPH scavenging ability at the concentration of TP ranged from 0.15-0.20g / mL. Furthermore, nanoemulsions prepared in this way also had a uniform particle size. Therefore, this nanoemulsions exhibited a good potential to act as an efficient emulsifier.