Exploring the mechanisms of neurotoxicity caused by fuzi using network pharmacology and molecular docking.

Safety has always been an important issue affecting the development of traditional Chinese medicine industry, especially for toxic medicinal materials, the establishment of risk prevention and control measures for toxic herbs is of great significance to improving the use of traditional Chinese medicine in clinical. Fuzi is a kind of traditional Chinese medicine and its toxicity has become the most important obstacle of limit in clinical using. In this paper, network pharmacology and molecular docking technology were used to analyze the main toxic components of Fuzi, the key targets and the mechanism of neurotoxicity. We carried out CCK-8 and WB assays, and detected LDH release and SDH activity. It was verified that aconitine caused neurotoxicity through a variety of pathways, including MAPK signaling pathway, pathways related to Akt protein, destruction of cell membrane integrity, damage of mitochondrial function affecting energy metabolism and apoptosis. What's more, this study confirmed that aconitine could produce neurotoxicity by promoting apoptosis of hippocampus neuron and decreasing its quantity through Nissl Staining and TUNEL assay. This paper found and confirmed multiple targets and various pathways causing neurotoxicity of Fuzi, in order to provide reference for clinical application and related research.

Qianliexin capsule exerts anti-inflammatory activity in chronic non-bacterial prostatitis and benign prostatic hyperplasia via NF-κB and inflammasome.

Qianliexin capsule (QLX) is a standardized traditional Chinese herbal preparation that has long been used to treat chronic non-bacterial prostatitis (CNP) and benign prostatic hyperplasia (BPH). This study investigated the anti-inflammatory activity of QLX in improving lower urinary tract symptoms (LUTS) associated with CNP and BPH. Rat models of CNP and BPH were induced by oestradiol or testosterone (hormonal imbalance) or chemical inflammation (carrageenan). QLX significantly relieved LUTS in CNP and BPH rat model by reducing prostate enlargement, epithelial thickness, pain response time, urine volume and bleeding time, and by improving prostatic blood flow. The expression of the pro-inflammatory cytokines interleukin (IL)-1ß and tumour necrosis factor (TNF)-α, the pro-inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and inflammasome components (NLRP3, caspase-1 and ASC) in CNP and BPH tissues was reduced by QLX addition. QLX treatment was followed by reduced cellular malondialdehyde and increased superoxide dismutase, catalase and glutathione peroxidase activity, consistent with antioxidant activity. Increases in Beclin-1 expression and the LC3II/I ratio following QLX treatment indicated that autophagy had been induced. QLX relieved LUTS in CNP and BPH rat models by inhibiting inflammation. The underlying mechanisms included inhibition of inflammasome activation, NF-κB activation, oxidant stress and autophagy.

Identification and Characterization of miRNAs in Self-Rooted and Grafted Malus Reveals Critical Networks Associated with Flowering.

Grafting can improve the agricultural traits of crop plants, especially fruit trees. However, the regulatory networks and differentially expressed microRNAs (miRNAs) related to grafting in apple remain unclear. Herein, we conducted high-throughput sequencing and identified differentially expressed miRNAs among self-rooted Fuji, self-rooted M9, and grafted Fuji/M9. We analyzed the flowering rate, leaf morphology, and nutrient and carbohydrate contents in the three materials. The flowering rate, element and carbohydrate contents, and expression levels of flowering genes were higher in Fuji/M9 than in Fuji. We detected 206 known miRNAs and 976 novel miRNAs in the three materials, and identified those that were up- or downregulated in response to grafting. miR156 was most abundant in Fuji, followed by Fuji/M9, and then self-rooted M9, while miR172 was most abundant in M9, followed by Fuji/M9, and then Fuji. These expression patterns suggest that that these miRNAs were related to grafting. A Gene Ontology (GO) analysis showed that the differentially expressed miRNAs controlled genes involved in various biological processes, including cellular biosynthesis and metabolism. The expression of differentially expressed miRNAs and flowering-related genes was verified by qRT-PCR. Altogether, this comprehensive analysis of miRNAs related to grafting provides valuable information for breeding and grafting of apple and other fruit trees.

A regulatory mutant on TRIM26 conferring the risk of nasopharyngeal carcinoma by inducing low immune response.

The major histocompatibility complex (MHC) is most closely associated with nasopharyngeal carcinoma (NPC), but the complexity of its genome structure has proven challenging for the discovery of causal MHC loci or genes. We conducted a targeted MHC sequencing in 40 Cantonese NPC patients followed by a two-stage replication in 1065 NPC cases and 2137 controls of Southern Chinese descendent. Quantitative RT-PCR analysis (qRT-PCR) was used to detect gene expression status in 108 NPC and 43 noncancerous nasopharyngeal (NP) samples. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to assess the transcription factor binding site. We discovered that a novel SNP rs117565607_A at TRIM26 displayed the strongest association (OR = 1.909, Pcombined = 2.750 × 10-19 ). We also observed that TRIM26 was significantly downregulated in NPC tissue samples with genotype AA/AT than TT. Immunohistochemistry (IHC) test also found the TRIM26 protein expression in NPC tissue samples with the genotype AA/AT was lower than TT. According to computational prediction, rs117565607 locus was a binding site for the transcription factor Yin Yang 1 (YY1). We observed that the luciferase activity of YY1 which is binding to the A allele of rs117565607 was suppressed. ChIP data showed that YY1 was binding with T not A allele. Significance analysis of microarray suggested that TRIM26 downregulation was related to low immune response in NPC. We have identified a novel gene TRIM26 and a novel SNP rs117565607_A associated with NPC risk by regulating transcriptional process and established a new functional link between TRIM26 downregulation and low immune response in NPC.