Four new alkaloids from the roots of Dactylicapnos scandens.

Four new alkaloids (1 - 4), together with five known ones (5 - 9), were isolated from the bulbs of Dactylicapnos scandens. The structures were determined by analysis of their spectroscopic data and quantum-chemical calculations. All the isolates were tested for their ability to modulate neuronal Ca2+ mobilization in primary cultured neocortical neurons. Compound 8 inhibited spontaneous Ca2+ oscillations at low micromolar concentrations.

Curcumin amends Ca2+ dysregulation in microglia by suppressing the activation of P2X7 receptor.

Curcumin (Cur) is widely used as an anti-inflammation agent and has anti-depression potential. Neuroinflammation mediated by Ca2+ channel activation is closely associated with the progression of post-stroke depression (PSD). In the current study, the role of P2X7 receptor (P2X7R) in the anti-PSD function of Cur was explored. Rats were subjected to middle cerebral artery occlusion (MCAO) surgery and chronic mild stress administration to induce PSD symptoms and then treated with Cur. The behaviors of rats were assessed with sucrose preference and forced swim tests. The accumulation of Ca2+ and the systemic inflammatory response in rats were detected. To determine the role of P2X7R in the anti-PSD function of curcumin, the PSD mice were further administrated with P2X7R agonist and antagonist. The administration of Cur attenuated behavior disorders associated with PSD. Moreover, the Ca2+ accumulation and the inflammatory response associated with PSD were also blocked by Cur. Cur also inhibited the activation of Ca2+ channel. The induced activity of P2X7R blocked the function of Cur by maintaining the symptoms of PSD in Cur-treated rats. Collectively, the anti-PSD function of Cur was dependent on the inhibition of P2X7R, which then deactivated Ca2+ channel-mediated inflammatory response associated with PSD progression.

Nobiletin suppresses high-glucose-induced inflammation and ECM accumulation in human mesangial cells through STAT3/NF-κB pathway.

Diabetic nephropathy (DN) is a complication of chronic diabetes and the main cause of end-stage renal disease all over the world. Inflammation and extracellular matrix (ECM) accumulation play important roles in the pathogenesis of DN. Evidence suggested that nobiletin acts anti-inflammatory role and plays a critical role in diabetes; however, its role in DN remains unclear. In the current study, we promulgated the nobiletin involved in high-glucose-induced glomerular mesangial cell inflammation and ECM accumulation. Nobiletin treatment significantly abrogated high-glucose-induced glomerular mesangial cell proliferation. Nobiletin treatment markedly suppressed inflammation cytokine secretion, including interleukin (IL)-1ß, IL-6, tumor necrosis factor α, and monocyte chemoattractant protein 1 in high-glucose-induced glomerular mesangial cell. Also, exposed nobiletin to high-glucose-induced glomerular mesangial cell considerably reduced ECM accumulation through inhibited ECM-associated protein type 4 collagen and fibronectin expression. Furthermore, nobiletin treatment abolished nuclear factor κB (NF-κB) pathway activation through signal transducer and activator of transcription 3 (STAT3) inhibition. Overexpression STAT3 reversed the effects of nobiletin on high-glucose-induced glomerular mesangial cell proliferation, inflammation, ECM accumulation, and NF-κB pathway activation. Hence, our results suggest that nobiletin play roles in high-glucose-induced glomerular mesangial cells through inhibiting inflammation and ECM accumulation, and the STAT3/NF-κB pathway was involved in the function of nobiletin.

Muscone improves hypoxia/reoxygenation (H/R)-induced neuronal injury by blocking HMGB1/TLR4/NF-κB pathway via modulating microRNA-142.

Previous reports have indicated that natural muscone has neuroprotective effects against cerebral hypoxia injury; however, little is known in regards to its pharmacological mechanism. In this study, we tried to evaluate the neuroprotective effects and mechanisms of muscone against cerebral hypoxia injury using an in vitro model. The cerebral hypoxia injury cell model was produced by hypoxia/reoxygenation (H/R). The cell viability and apoptosis were measured using the cell counting Kit-8 and the Annexin V-FITC/PI Apoptosis Detection kit, respectively. To screen microRNAs regulated by muscone, we analyzed the gene expression datasets of GSE84216 retrieved from gene expression omnibus (GEO). Here, it was demonstrated that muscone treatment significantly alleviated the cell apoptosis, oxidative stress and inflammation in H/R-exposed neurons. Subsequently, through analyzing GSE84216 from the GEO database, miR-142-5p was markedly upregulated by treatment of muscone in this cell model of cerebral hypoxia injury. Further experiments revealed that downregulation of miR-142-5p eliminated the neuroprotective effects of muscone against H/R induced neuronal injury. Additionally, high mobility group box 1 (HMGB1), an important inflammatory factor, was identified as a direct target of miR-142-5p in neurons. Meanwhile, we further demonstrated that muscone could reduce the expression of HMGB1 by upregulating miR-142-5p expression, which subsequently resulted in the inactivation of TLR4/NF-κB pathway, finally leading to the improvement of cell injury in H/R-exposed neurons. Overall, we demonstrate for the first time that muscone treatment alleviates cerebral hypoxia injury in in vitro experiments through blocking activation of the TLR4/NF-κB signaling pathway by targeting HMGB1, suggesting that muscone may serve as a potential therapeutic drug for treating cerebral hypoxia injury.

Baicalin suppresses lung cancer growth phenotypes via miR-340-5p/NET1 axis.

As a malignant disease, lung cancer has a high morbidity and mortality rate. Baicalin is derived from Radix Scutellariae and has anti-tumor effects, however, its role in lung cancer remains unknown. Here, functional assays suggested baicalin suppressed in vitro lung cancer phenotypes. We used micro (mi)RNA array analysis to explore baicalin effects on miRNA expression. We observed baicalin increased miR-340-5p expression, whereas inhibition of this expression abolished anti-tumor effects of baicalin. Furthermore, neuroepithelial cell transforming 1 (NET1) functioned as a miR-340-5p target, and acted in a baicalin-dependent manner to regulate lung cancer progression. Thus, baicalin elicited antitumor activities by affecting the miR-340-5p/NET1 axis, suggesting a new approach to lung cancer clinical management.

Effects of long-term phosphorus application on crop yield, phosphorus absorption, and soil phosphorus accumulation in maize-wheat rotation system.

In this study, we examined the effects of four phosphorus treatments on crop yields, and analyzed crop phosphorus uptake and phosphorus utilization efficiency, as well as changes in soil phosphorus deficit in maize-wheat rotation system, based on a 7-year field experiment in Baoding City, Hebei Province. The results showed that long-term phosphorus application significantly increased the yield and phosphorus uptake of maize and wheat. The yield and phosphorus uptake of maize and wheat showed a parabolic trend that first increased and then decreased with the increases of phosphorus application. The utilization efficiency of phosphorus fertilizer in the corn season was higher than that in the wheat season under various phosphorus application treatments. The cumulative utilization efficiency of phosphorus fertilizer in the wheat season showed a downward trend. The decline rate showed that optimized phosphorus application > 70% optimized phosphorus application >130% optimized phosphorus application. The cumulative utilization efficiency of phosphorus fertili-zer in the corn season showed an upward trend. For the rising rate, the optimized phosphorus application > 70% optimized phosphorus application > 130% optimized phosphorus application. Both the apparent phosphorus surplus and the accumulated phosphorus surplus of the soil without phosphorus application were under phosphorus deficiency. Under the treatment of phosphorus application, soil phosphorus showed a status of phosphorus surplus. The higher the phosphorus application rate, the longer the accumulation period, the higher the soil phosphorus surplus. Under the straw returning condition, phosphorus application rate for wheat of 105-150 kg·hm-2 and the phosphorus application rate for maize of 63-90 kg·hm-2 in Hebei fluvo-aquic soil could ensure the high crop yield, keep the phosphorus utilization efficiency at a high level, and reduce soil phosphorus accumulation and environmental risks.

circFADS2 regulates lung cancer cells proliferation and invasion via acting as a sponge of miR-498.

CircRNAs could play critical functions in tumor progression. However, the expression and underlying mechanism of circRNAs in lung cancer progression remain poorly defined. In the present study, high-throughput microarray assay revealed that hsa_circRNA_100833 (identified as circFADS2) was markedly evaluated in lung cancer tissues, and it was further validated by qRT-PCR. High expression of circFADS2 was correlated with advanced TNM stage, lymph node metastasis, poor differentiation, and shorter overall survival of NSCLC patients. In vitro assays results showed that circFADS2 inhibition suppressed lung cancer cells proliferation and invasion ability. Bioinformatics analysis showed that miR-498 contained the complementary binding region of circFADS2, which was confirmed by Dual-luciferase reporter assay. In addition, the expression of miR-498 was down-regulated and negatively associated with circFADS2 expression in nonsmall cell lung cancer. Furthermore, rescue assays showed that miR-498 inhibitors abolished the effects of circFADS2 inhibition on lung cancer cells progression. Taken together, our findings indicated that circFADS2 was an effective tumor promoter in lung cancer progression, and its functions were performed by regulating the expression of miR-498. These data suggested that circFADS2 could act as a target for lung cancer treatment.