Targeted drug delivery systems for elemene in cancer therapy: The story thus far.

Elemene (ELE) is a group of broad-spectrum anticancer active ingredients with low toxicity extracted from traditional Chinese medicines (TCMs), such as Curcumae Rhizoma and Curcuma Radix, which can exert antitumour activities by regulating various signal pathways and targets. However, the strong hydrophobicity, short half-life, low bioavailability and weak in vivo targeting ability of ELE restrict its use. Targeted drug delivery systems based on nanomaterials are among the most viable methods to overcome these shortcomings. In this review, we first summarize recent studies on the clinical uses of ELE as an adjunct antitumour drug. ELE-based combination strategies have great promise for enhancing efficacy, reducing adverse reactions, and improving patients' quality of life and immune function. Second, we summarize recent studies on the antitumour mechanisms of ELE and ELE-based combination strategies. The potential mechanisms include inducing pyroptosis and ferroptosis, promoting senescence, regulating METTL3-mediated m6A modification, suppressing the Warburg effect, and inducing apoptosis and cell cycle arrest. Most importantly, we comprehensively summarize studies on the combination of targeted drug delivery systems with ELE, including passively and actively targeted drug delivery systems, stimuli-responsive drug delivery systems, and codelivery systems for ELE combined with other therapies, which have great promise in improving drug bioavailability, increasing drug targeting ability, controlling drug release, enhancing drug efficacy, reducing drug adverse effects and reversing MDR. Our summary will provide a reference for the combination of TCMs such as ELE with advanced targeted drug delivery systems in the future.

Idebenone-Activating Autophagic Degradation of α-Synuclein via Inhibition of AKT-mTOR Pathway in a SH-SY5Y-A53T Model of Parkinson's Disease: A Network Pharmacological Approach.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, which currently lacks disease-modifying therapy to slow down its progression. Idebenone, a coenzyme Q10 (CQ10) analogue, is a well-known antioxidant and has been used to treat neurological disorders. However, the mechanism of Idebenone on PD has not been fully elucidated. This study aims to predict the potential targets of Idebenone and explore its therapeutic mechanism against PD. METHOD: We obtained potential therapeutic targets through database prediction, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Next, we constructed and analyzed a protein-protein interaction network (PPI) and a drug-target-pathway-disease network. A molecular docking test was conducted to identify the interactions between Idebenone and potential targets. Lastly, a PD cell line of SH-SY5Y overexpressing mutant α-synuclein was used to validate the molecular mechanism. RESULT: A total of 87 targets were identified based on network pharmacology. The enrichment analysis highlighted manipulation of MAP kinase activity and the PI3K-AKT signaling pathway as potential pharmacological targets for Idebenone against PD. Additionally, molecular docking showed that AKT and MAPK could bind tightly with Idebenone. In the cell model of PD, Idebenone activated autophagy and promoted α-synuclein degradation by suppressing the AKT/mTOR pathway. Pretreating cells with chloroquine (CQ) to block autophagic flux could diminish the pharmacological effect of Idebenone to clear α-synuclein. CONCLUSION: This study demonstrated that Idebenone exerts its anti-PD effects by enhancing autophagy and clearance of α-synuclein, thus providing a theoretical and experimental basis for Idebenone therapy against PD.

Mechanism of Chaihu Shugansan on Syndrome of Liver Stagnation / 中国实验方剂学杂志

Chaihu Shugansan is a representative prescription for soothing the liver and relieving depression in traditional Chinese medicine(TCM). Chaihu Shugansan is from Jingyue Quanshu.Chaihu Shugansan has been widely used in clinic since Ming dynasty because of its exact curative effect.Chaihu Shugansan has the effect in soothing the liver and relieving depression through multiple components, multiple ways and multiple targets.At present, the mechanism of Chaihu Shugansan has been interpreted based on its multiple effect on neurotransmitters, cytokines, neuronal injury signal pathways, neuroendocrine, oxidative stress and so on.This paper summarizes the progress of clinical studies on source, pharmacology of single herbs and effective components of Chaihu Shugansan, in aspects of cardiovascular system, neuropsychiatric system, digestive system, reproduction-related systems, analyses and summarizes relevant literatures of Chaihu Shugansan published in recent years, and discusses about current development and shortcomings of Chaihu Shugansan, so as to provide ideas for the studies in the future.Beneficial explorations will be conducted in large-sample-size, standardized, clinical and experimental mutual verification.In proteomics research technology, network pharmacology, supramolecular theory of TCM and other fields, Chaihu Shugansan and liver depression syndrome will be organically connected from the microscopic perspective.And comprehensive studies will be conduct to TCM, metabonomics, proteomics, genomics and other disciplines, in order to clarify Chaihu Shugansan prescriptions, syndromes, therapeutics and its mechanism.

[Different aluminum adjuvants significantly enhances the effect of immunization on Brucella Omp31].

Objective To investigate the effect of aluminum phosphate (AP) and aluminum hydroxide (AH) as adjuvants on Brucella outer membrane protein 31 (Omp31) in inducing humoral and cellular immune responses and immune protection. Methods AP and AH adjuvants were prepared and separately mixed with Brucella Omp31 protein to measure the adsorption rates. The AP- and AH-absorbed Omp31 protein were intraperitoneally injected into BLAB/c mice at 0, 2, and 4 weeks, and meanwhile, unabsorbed Omp31 protein and PBS were used as controls. The levels of serum IgG, IgG1, IgG2a and genital tract secretion sIgA were determined by ELISA at 0, 2, 4 and 6 weeks. Spleen cells were collected for culture at 6 weeks, and the cells were stimulated by Omp31 for 48 hours followed by the analysis of IFN-γ and IL-10 levels in the supernatants by ELISA, and the determination of lymphocyte proliferation by CCK-8 assay. The mice were challenged with Brucella at 6 weeks, and bacterial content in spleen tissue was determined 1 and 2 weeks later. Results AP and AH could absorb over 70% and 85% of the Omp31 protein, respectively, for solutions at all the tested concentrations. ELISA suggested that serum IgG, IgG1, IgG2a and genital tract sIgA levels peaked 2 weeks after the last immunization for both AP and AH groups, and antibody level was higher in the AP and AH groups than the control groups, and higher in the AH group than in the AP group. CCK-8 assay showed that the proliferating rate of lymphocytes induced by the AH group was significantly higher than that by the AP group, and the AH group also showed significantly higher IFN-γ level in the supernatant than the AP group, but no significant difference in IL-10 level. The AH group had remarkably lower bacterial load in the spleen than the AP group 2 weeks after challenged by Brucella 16M strain. Conclusion Both AP and AH adjuvants effectively enhanced immunogenicity and immune protection of the Brucella Omp31 protein, and AH was superior to AP in this respect.

[Effects of Serum Containing Qinbai Qinfei Concentrated Pellets on Expressions of NLRP3 Inflammasome in RAW264.7 Cells Infected with Mycoplasma pneumonia].

Objective: To investigate the effects of serum containing Qinbai Qingfei concentrated pellets on expressions of NLRP3 inflammasome in RAW264. 7 cells infected with Mycoplasma pneumoniae( MP) IL-1ß. Methods: RAW264. 7 cells were randomly divided into normal group, MP model group and serum containing Qinbai Qinfei concentrated pellets group. RAW264. 7 cells and MP strain were cultured utilizing normal methods, preparation of serum containing Qinbai,with 1∶ 10 multiplicity of infection( MOI) of MP stimulation on RAW264. 7 cells; cells of each group were collected at 8,16,24 h respectively. The expressions of NLRP3,ASC and Caspase-1 mRNA were detected by the method of FQ-PCR. The expressions of NLRP3,ASC and Caspase-1 p20 protein were detected by Westernblot. The content of IL-1ß in the supernatant was measured by ELISA. Results: Compared with the normal group, he levels of NLRP3,ASC and Caspase-1 mRNA were significantly increased in the model group at 8,16,24 h respectively( P < 0. 05 or P < 0. 01); while the levels of NLRP3,ASC and Caspase-1 p20 protein were increased significantly( P < 0. 05 or P < 0. 01) at 16,24 h, and the levels of IL-1ß were increased at significantly( P < 0. 01) 24 h. Compared with the model group, the levels of NLRP3,ASC and Caspase-1 mRNA were significantly reduced in serum containing Qinbai Qinfei concentrated pellets group at 16,24 h( P < 0. 05 or P < 0. 01); the expressions of NLRP3,ASC,Caspase-1 p20 protein and the content of IL-1ß were all decreased at 24 h.Conclusion: The mechanism of antiMycoplasma pneumoniae action of Qinbai may be related to the down-regulation of NLRP3 inflammasome expressions.

[Diagnosis of phosphorus nutrition in winter wheat based on first derivative spectra and radial basis function neural network].

The hyperspectral leaf reflectance in winter wheat was measured under 4 phosphorus levels at different growth stages, i.e. revival stage, jointing stage, tassel stage and grouting stage. And their first derivative of spectra were calculated and denoised by the threshold denoising method based on wavelet transform. After studying characteristics of the two kinds of spectra resulting from different phosphorus contents levels as well as correlations between leaf phosphorus contents and spectral values, sensitive wavebands and four kinds of absorption areas were extracted. Then the four kinds of absorption areas and their corresponding leaf phosphorus content were normalized and input to RBFNN. Results show that: (1) Sensitive wavebands for monitoring leaf phosphorus contents in original leaf spectra are 426-435 and 669-680 nm. (2) Sensitive wavebands in first derivative of spectra are 481-493 and 685-696 nm. (3) Trained RBFNN can learn and seize the linearity/non-linearity mapping between samples and output targets.