Paeonol suppresses fibroblast synovitis by increasing MANF expression / 中国药理学通报

Aim To investigate the possible mechanism of paeonol inhibiting the inflammatory response of fibroblast synovial cells (RA-FLSS) in rheumatoid arthritis. Methods CCK-8 assay was used to detect Paeonol's inhibitory level on the abnormal proliferation of arthritis human fibroblast synovial cells (RA-FLSs). The levels of endoplasmic reticulum stress-related proteins MANF and ATF6 were detected by Western blot. Cell localization of transcription factor p65 and Mesencephalic Astrocyte Derived Neurotrophic Factor (MANF) was detected by immunofluorescence. RT-qPCR detected the changes of p65 target genes. Results Paeonol could significantly inhibit the abnormal proliferation of RA-FLSS cells. Paeonol activates ATF6 and increases the expression of MANF. Paeonol promoted the nuclear transfer of MANF protein and inhibited the transcriptional activity of p65. Conclusion Paeonol promotes the expression of MANF and nuclear transfer through the endoplasmic reticulum stress pathway and affects the progression of RA by inhibiting the transcriptional activity of p65.

Resveratrol mediates apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis by down-regulating mnsod / 中国药理学通报

Aim: To investigate the role of manganese superoxide dismutase (MS0D) protein expression in the proliferation and apoptosis of fibroblast-like synoviocyte (RA-FLS) in rheumatoid arthritis mediated by resveratrol(Res). Methods: After RA-FLSs was treated with Res, the expression of MnSOD protein was detected by CCK-8 method, and the expression of Mn- SOD protein was detected by, Western blot. After lentivirus infection with RA-FLSs, 8 mg · L-1 purine mycin was used to screen the infected cells, and three stable cell lines were established; MnSOD overexpression, MnSOD interference and MnSOD control. The mitochondria reactive oxygen species (mtROS) levels of each cell line treated with 5 μmol · L-1 hydrogen peroxide (H2O2) and 200 mol · L-1 Res were detected by laser confocal microscopy, and cell apoptosis was detected by flow cytometry. Results Res could inhibit the proliferation and the expression of MnSOD in RA- FLSs. The lentivirus-mediated MnSOD regulation could significantly increase or decrease the expression of Mn- SOD in RA-FLSs. MnSOD over expression could decrease the level of mtROS and apoptosis of the RA- FLSs treated with 5 μmol · L-1 H2O2 and 200 μmol · L-1 Res. While the MnSOD RNAi showed the opposite results. Conclusions: Res may up-regulate mtROS levels by inhibiting the expression of MnSOD, thus promoting the apoptosis of RA-FLSs.

Preliminary investigation of TIM-3 ligand galectin-9 inducing apoptosis of NK/T cell lymphoma cells / 中国肿瘤生物治疗杂志

@# Objective: To identify the expression pattern of TIM-3 in natural killer/T-cell lymphoma (NK/TCL) cell lines, and to investigate the effect and mechanism of its ligand galectin-9 (GAL-9) inducing apoptosis of NK/TCL cell lines. Methods: Expression of TIM-3 in NK cell of peripheral blood from healthy donors and NK/TCL cell lines (SNK-1、SNK-6、SNT-8) was detected by Western blotting. After being treated with rhGAL-9 at various concentrations for 24h, the cell proliferation ability was analyzed with CCK-8 assay. Apoptosis ratio of the cells was determined by flow cytometry. Expressions of caspase-3, PARP and their cleavages were detected by Western blotting; moreover, phosphorylation levels of proteins in MAPK signaling pathway were also detected by Western blotting. Results: The expression of TIM-3 in SNK-1, SNK-6 and SNT-8 cell lines was significantly higher than that of NK cells from healthy donors (P<0.05). CCK-8 result showed that rhGAL-9 obviously inhibited the proliferation of NK/TCL cell lines in a concentration dependent manner. Flow cytometry showed that rhGAL-9 induced the apoptosis of NK/TCLcells; and Western blotting proved that the expression of cleaved caspase-3, cleaved-PARP, and p-JNK in MAPK signaling pathway were significantly elevated. Conclusion: TIM-3 was over-expressed in NK/TCL cell lines, and its ligand galectin-9 induced cell apoptosis probably through the activation of JNK kinase pathways.

Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals protective roles of RAS-RAF-MEK signaling

Neuronal atrophy is a common pathological feature occurred in aging and neurodegenerative diseases. A variety of abnormalities including motor protein malfunction and mitochondrial dysfunction contribute to the loss of neuronal architecture; however, less is known about the intracellular signaling pathways that can protect against or delay this pathogenic process. Here, we show that the DYNC1I1 deficiency, a neuron-specific dynein intermediate chain, causes neuronal atrophy in primary hippocampal neurons. With this cellular model, we are able to find that activation of RAS-RAF-MEK signaling protects against neuronal atrophy induced by DYNC1I1 deficiency, which relies on MEK-dependent autophagy in neuron. Moreover, we further reveal that BRAF also protects against neuronal atrophy induced by mitochondrial impairment. These findings demonstrate protective roles of the RAS-RAF-MEK axis against neuronal atrophy, and imply a new therapeutic target for clinical intervention.

Study on between magnetic resonance venography and digital subtraction angiography on the inferior vena cava obstructive interface morphology of Budd-Chiari syndrome / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate magnetic resonance venography (MRV) in diagnosing obstructive interface morphology of Budd-Chiari syndrome(BCS).</p><p><b>METHODS</b>MRV examination was performed on 44 cases of BCS, and the images of obstructive interface morphology of the inferior vena cava were reviewed by two radiologists.</p><p><b>RESULTS</b>In all 44 cases, there were 37 cases with complete obstruction and 7 with incomplete obstruction. MRV showed 4 cases with membrane with hole of incomplete obstruction. The morphologies MRV demonstrated that the proximal part of the 37 cases with complete obstruction were mainly divided into the cone type (36 cases) and the planum type (1 case). Besides, the type of distal end of obstruction were the cone type (30 cases), the planum type (4 cases) and the irregular type (3 cases). The overall sensitivity, specificity, positive and negative predictive values for the diagnosis of MRV were respectively 100%%, 57.1%, 92.5% and 100% as compared to the DSA.</p><p><b>CONCLUSION</b>The examination of MRV is capable of revealing the obstructive interface morphology of the inferior vena cava, especially for the distal end of obstruction. MRV can provide guidelines in interventional treatment of Budd-Chiari syndrome.</p>