As the primary innate immune cells in the central nervous system, microglia can be activated by external noxious stimulus and in turn interact with astroglia and neurons to induce neuroinflammation and facilitate the transmission of pain signals. This response can help the central nervous system adapt to the changes of the internal environment induced by noxious stimulus, leading to the long-term sensitivity of peripheral and central pain nerve conduction pathways and chronic neuropathic pain. Numerous researches found that activation of microglia participated in the occurrence and maintenance of chronic neuropathic pain, and inhibition of microglial activation in the spinal cord or the brain had analgesic effect in animal experiments. Due to the fact that molecular and cellular mechanisms between the activation of microglia and pain remittence are unclear, there are many difficulties in designing of new drugs selectively targeting to the activation of microglia for treatment of chronic neuropathic pain. We review here the research articles on microglia and chronic neuropathic pain, sorting out the relationship between microglia and chronic neuropathic pain, and provide new ideas for the development of new drugs targeting to microglia for the treatment of chronic neuropathic pain.

Using column chromatographic and preparative HPLC technologies, we isolated a new sesquiterpene glycoside from the stem of Dendrobium nobile. With spectroscopic techniques including NMR and MS, the new compound was identified as cadalene-12-O-β-D-glucopyranoside. This type of compound was dehydrogenated from cadinane sesquiterpene to achieve a naphthalene ring, and it is rare from a natural resource.

This study aims to investigate the effect of down-regulation of miR-205-5p by transfection of miR-205-5p inhibitor on the sensitivity of HNE1/DDP cells to cisplatin (DDP) induced apoptosis and explore the underlying mechanism. qRT-PCR was used to detect the expression of miR-205-5p in HNE1 or HNE1/DDP cells. The expression level of miR-205-5p was analyzed after transfecting HNE1/DDP cells with miR-205-5p inhibitor. MTT assay was used to evaluate the inhibitory effect of DDP alone or in combination with miR-205-5p inhibitor on the proliferation of HNE1/DDP or HNE1 cells. Apoptosis of cells treated with miR-205-5p inhibitor alone or in combination with DDP (8 μmol·L^-1) was assessed using flow cytometry with PI staining, with the nucleus was counterstained with DAPI staining. The expression of Bax, Bak, Mcl-1, or Bcl-2 was analyzed by Western blot. HNE1/DDP cells showed a high level of expression of miR-205-5p, and the expression of miR-205-5p was significantly decreased by transfection of miR-205-5p inhibitor. Down-regulation of miR-205-5p significantly increased the sensitivity of HNE1/DDP cells to DDP (P < 0.05). Transfection of miR-205-5p inhibitor enhanced the sensitivity of HNE1/DDP cells to DDP induced apoptosis. Treatment of HNE1/DDP cells with miR-205-5p inhibitor combined with DDP (8 μmol·L^-1) for 24 h resulted in an apoptotic rate of 28.93% ±2.50%, significantly higher than that treated with miR-205-5p inhibitor (9.83% ±1.31%) or DDP alone (10.83% ±1.70%) (P < 0.05). DAPI staining showed that HNE1/DDP cell nucleus became significantly condensed and fragmented in miR-205-5p inhibitor combined with DDP group. The combined group up-regulated the expression of Bax and down-regulated the expression of Bcl-2 in HNE1/DDP cells. Therefore, down-regulation of miR-205-5p can enhance the sensitivity of HNE1/DDP cells to cisplatin induced apoptosis, and the mechanism may involve up-regulation of Bax and down-regulation of Bcl-2 expression.

In this manuscript, a rapid and simple analysis method for aconitine alkaloids was established. The method was based on the use of direct ionization and wooden tip spray ionization technology to detect the aconite. The aconite tuber slices were wrapped with wet filter paper overnight, cut into triangles, and extracted with a few solvents for direct ionization and wooden tip spray mass spectrometry. The results showed that alkaloids in aconite tuber can be rapid detected by two mass spectrometric methods without tedious sample pretreatment. Both methods are superior to that of traditional capillary electrospray ionization mass spectrometry (ESI-MS). The direct ionization MS is better than the wooden tip spray MS for analysis of aconite except under the condition of methylene chloride as extract or spray solvent. Different types of alkaloids in aconite tuber can be selectively detected when different solvents are used. The experiments provide a rapid and no pretreatment MS spectrometric method for analysis of alkaloids in aconite. These sample methods are important for research on aspects of plant varieties, storage, prescription compatibility, and quality control of aconite.

Foxo-1 plays an important role in development of muscle atrophy, serving as a potential target for therapeutic treatment of the disease. In this study, the Foxo-1 mRNA was targeted by a Foxo-1 specific RNA oligonucleotide modified by 2'-O-methyl and with a butanol tag at the 3'-end. To understand the in vivo significance of new modified RNA oligos, efficacy, pharmacokinetic and safety profiles of the new modified RNA oligonucleotide targeting Foxo-1 were evaluated in mice. All experimental protocols were approved by the Animal Ethics Committee of Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention. The results showed that different doses of the RNA oligonucleotide can reduce the expression of Foxo-1 in mice by two routes of administration, leading to an increase in skeletal muscle mass of the mice. The results of pharmacokinetic evaluation showed that the plasma disappearance curve for the RNA oligonucleotide could be described by a two-compartmental model. The results of safety evaluation showed that no obvious adverse effects on renal and hepatic functions, nor on hematological parameters by intravenous or oral administration of the RNA oligo with a maximum dose of 30 mg·kg^-1. Histopathology also did not reveal any significant changes in the morphology of the organs studied. In conclusion, the new modified RNA oligo is safe and effective in mice, providing experimental evidence supporting the significance for its clinical application.

Codeine-O-demethylase (CODM) is a key enzyme in the biosynthesis of codeine and morphine. In this study, CODM gene sequences were cloned from Papaver somniferum and Papaver rhoeas, and were compared with each other by sequence alignment and bioinformatics analysis. The results showed that there were three genotypes of CODM in Papaver somniferum and five genotypes of CODM in Papaver rhoeas. Bioinformatics analysis showed that all CODM proteins had no signal peptide sequence, and these proteins were predicted to be non-secretory proteins, belonging to the Pcbc supergene family. Although the amino acid sequences of CODM in poppies are the same, the expression levels of CODM in different poppy resources are significantly different. It is speculated that the variation of transcription level of CODM may be related to its non-coding region sequence, which lays a foundation for further research on the synthesis and regulation mechanism of alkaloids in poppies.

To explore the effect of total extract of Chrysanthemum morifolium on lipopolysaccharide (LPS)-induced acute lung injury in mice, we studied the effects of three caffeoyl quinic acids isolated from Chrysanthemum morifolium on vascular endothelial cell injury and their mechanisms of action. All animal experiments were carried out strictly in accordance with the National Animal Welfare Ethics and Protection Regulations. A mouse model of acute lung injury was established by intranasal instillation of LPS. After 6 days of oral administration of chrysanthemum extract, the lung wet weight/dry weight ratio, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured in mouse bronchoalveolar lavage fluid. Human umbilical vein endothelial cells (HUVEC) were serum starved for 12 h and treated with 2.5 μg·mL^-1 LPS for 24 h to establish the in vitro model of vascular endothelial cell injury. After 24 h of treatment of caffeoyl quinic acids from Chrysanthemum morifolium, the levels of TNF-α, IL-6, IL-1β, vascular cell adhesion molecule-1 (VCAM-1) and endothelin-1 (ET-1) were measured by ELISA in the cell culture supernatant, the malondialdehyde (MDA) level was detected by TBA method, the superoxide dismutase (SOD) level was determined by hydroxylamine method, and the nitric oxide (NO) level was assayed by a one-step method. The levels of p-MEK1/2, MEK1/2, p-ERK1/2, ERK1/2, p-JNK, JNK, p-P38 and P38 of mitogen-activated protein kinase (MAPK) signaling pathway were detected by Western blot. The total extract of Chrysanthemum morifolium can significantly reduce the wet weight/dry weight ratio of lung in mice and the levels of TNF-α, IL-6 and IL-1β in alveolar lavage fluid. The caffeoyl quinic acids from Chrysanthemum morifolium significantly increased the levels of SOD and NO, decreased the levels of TNF-α, IL-6, IL-1β, VCAM-1, ET-1 and MDA, and significantly reduced the levels of p-MEK1/2, p-ERK1/2. In conclusion, total extracts of Chrysanthemum morifolium exhibit certain protective effect on mice with acute lung injury, and three caffeoyl quinic acids from Chrysanthemum morifolium may improve LPS-induced vascular endothelial cell injury by inhibiting inflammatory cytokines and oxidative stress, and regulating inter-cellular adhesion molecule and vasomotor factors through ERK/MAPK signaling pathway.

CY-1-4 is a tryptanthrin derivative exhibiting antitumor activity. The solubility of CY-1-4 was poor and the corresponding mechanism needs further study. To solve this problem, we prepared nanoparticles encapsulated with CY-1-4 (CY-1-4 NPs) by nanoprecipitation method using poly(caprolactone) (PCL) and poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-PCL) as carriers to improve solubility. We then explored whether CY-1-4 NPs induced B16-F10 cytotoxicity via ferroptosis by determining the effect of CY-1-4 NPs on reactive oxygen (ROS) levels, repairing efficacy of lipid reactive oxygen inhibitor ferrostatin-1 and iron chelator deferoxamine (DFO), and potentiation of protoporphyrin (PPIX) induced B16-F10 cell death. The results showed that nanoparticlated strategy significantly improved solubility of CY-1-4. With the particle size about 116 nm, encapsulating efficacy was about 83% and the drug loading capacity was about 4.80%. Ferroptosis mechanistic studies indicated that CY-1-4 NPs could improve the ROS level in B16-F10 cells, whereas ferrostatin-1 and DFO could partly inhibited the cytotoxicity and PPIX could potentiated the cytotoxicity of CY-1-4 NPs in B16-F10 cells. These results showed that ferroptosis was one of the cell death mechanisms induced by tryptanthrin derivative CY-1-4 nanoparticle.

The chemical constituents of Viburnum taitoense Hayata were investigated using column chromatography silica gel and Sephadex LH-20, etc. Seven pentacyclic triterpenoids were isolated and their structures were elucidated by spectral data and physicochemical properties as 3β, 6β-dihydroxy olean-11, 13(18)-dien-28-acid (1), 3β-hydroxy olean-11, 13(18)-diene-28-acid (2), 12-ene-olean-28-acid-3β-palmitate (3), 3β-acetylcocodiol (4), corosolic acid (5), uvaol (6) and ursolic acid (7). Among them, compound 1 is a new oleanane type triterpenoid and its absolute configuration was confirmed by single-crystal X-ray diffraction data. Compounds 2-5 were isolated from this genus for the first time. All the compounds were evaluated for their anti-inflammatory activities in vitro, and compound 5 showed significant inhibitory activity against nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells with an IC₅₀ of 25.52 ±0.56 μmol·L^-1 when compared to the positive control, quercetin (IC₅₀ of 25.46 ±0.62 μmol·L^-1).

Immunotherapy is the most active research area for cancer treatment. Tumor vaccine is one of the most developed aspects of cancer immunotherapy. Though tumor vaccine has made many breakthrough, it still faces many challenges. In this study, we coated the black phosphorus quantum dots (BPQDs) with cancer cell membrane to create a nanoparticle named BPQD-CCNVs. The BPQD-CCNVs were incubated with bone marrow-derived dendritic cells and irradiated with 808 nm infrared light. We tested the expression level of CD80, CD86 and MHC Ⅱ of dendritic cells by flow cytometry after irradiation. All animal experiments approved by the Animal Experiments Ethical Committee of Tsinghua University. The results showed that the rise of medium's temperature caused by the photothermal effect of BPQDs could upregulate the expression of CD80, CD86 and MHC-Ⅱ on dendritic cell surface. Based on these, we conclude that near infrared irradiation can stimulate the activation of dendritic cells. Our study may have provided a new strategy for tumor vaccine development.