OBJECTIVE: To explore the correlation between the interleukin-17 (IL-17) level of peripheral blood and aggression of bipolar mania. METHODS: Thirty-six patients of bipolar mania were selected as experimental group by DSM-IV-TR and received treatment with quetiapine and lithium. Thirty-six healthy volunteers with similar age and gender were selected as control group. The level of IL-17 at baseline in each group and the level of IL-17 in the experimental group after treatment for 2, 4 and 8 weeks were detected by ELISA. RESULTS: The level of IL-17 in experimental group at baseline, after treatment for 2 and 4 weeks were all significantly higher than that in control group. After 8 weeks treatment, there was no significant difference between the two groups (P > 0.05). After 2, 4 and 8 weeks treatment, the total score and aggression score of Young Mania Rating Score (YMRS) were significantly lower than the baseline level (P < 0.05). In experimental group, the level of IL-17 was positively correlated with the two scores of YMRS at baseline (P < 0.05). CONCLUSION Bipolar mania may be related to the up-regulation of IL-17. The level of IL-17 is related to the severity of manic symptoms at baseline, especially aggression symptom.
Aggression/drug effects* ; Antipsychotic Agents/therapeutic use* ; Biomarkers/blood* ; Bipolar Disorder/drug therapy* ; Case-Control Studies ; Diagnostic and Statistical Manual of Mental Disorders ; Double-Blind Method ; Humans ; Interleukin-17/metabolism* ; Lithium Compounds/therapeutic use* ; Quetiapine Fumarate/therapeutic use* ; Treatment Outcome

The aim of this study was to investigate whether and how phosphodiesterase (PDE) inhibitors modulate the proliferation, cell cycle and apoptosis in lymphoma cells. The effects of aminophylline (AM), a non-specific PDE inhibitor, on Raji cells were explored in vitro. MTT assay, light and transmission electron microscopy and annexin V staining were used to observe cell proliferation, morphologic changes and apoptosis rate in AM-treated cells, and FCM and RT-PCR techniques were adopted to detect the effect on cell cycle, the expression of cyclin B1 and Bcl-2 and mitochondrial transmembrane potential in AM-treated cells. The results showed that AM inhibited the growth of Raji cells in a concentration-dependent manner. Morphologic observations showed apoptosis changes in AM-treated cells, including cytoplamic shrinkage, cytoplasmic bubbling, karyopyknosis and nuclear fragmentation. FCM and RT-PCR detection showed that AM intervention increased the fraction of annexin V(+) cells, reduced the value of mitochondrial transmembrane potential, induced S phase arrest, and down-regulated the expression of Bcl-2 at both mRNA and protein level and cyclin B1 protein in a concentration-dependent manner. It is concluded that PDE inhibitor aminophylline may induce Raji cell growth inhibition, S phase arrest, apoptosis via down-regulation of Bcl-2 and reduction of mitochondrial transmembrane potential.
Aminophylline ; pharmacology ; Apoptosis ; drug effects ; Burkitt Lymphoma ; drug therapy ; genetics ; pathology ; Cell Division ; drug effects ; Cyclin B ; genetics ; metabolism ; Cyclin B1 ; Dose-Response Relationship, Drug ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Intracellular Membranes ; drug effects ; physiology ; Membrane Potentials ; drug effects ; Mitochondria ; drug effects ; physiology ; Phosphodiesterase Inhibitors ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; RNA, Messenger ; drug effects ; genetics ; metabolism ; S Phase ; Tumor Cells, Cultured ; drug effects ; metabolism ; ultrastructure

In order to investigate the role and the mechanism of protein tyrosine phosphatase (PTPase) signaling pathway in the regulation of proliferation, cell cycle and apoptosis in lymphoma cells, the effects of sodium orthovanadate, Na(3)VO(4), a specific PTPase inhibitor, were explored on Raji lymphoblast-like cell line by MTT assay and CFU-Raji culture, morphologic observation, DNA gel electrophoresis, FCM and RT-PCR. Results showed that MTT assay and CFU-Raji culture demonstrated that sodium or thovanadate inhibited the growth of Raji cells in a concentration-dependent fashion; morphologic observations showed that Raji cells exhibited cytoplasm shrinkage, cytoplasm membrane blebbing, nuclear fragmentation and chromatin condensation forming crescents along nuclear membrane characteristic of apoptosis in the presence of Na(3)VO(4); DNA gel electrophoresis revealed typical DNA ladder reminiscent of DNA cleavage at internucleosomal sites in Na(3)VO(4) treated cells; FCM and RT-PCR indicated that Na(3)VO(4) intervention increased the fraction of annexin V(+) PI(-) cells, reduced the value of mitochondrial transmembrane potential, induced G(2)/M arrest and down-regulated the expression of Bcl-2 and cyclin B1 at both mRNA and protein level in a concentration-dependent manner. It was concluded that PTPase pathway might be implicated in the regulation of cell proliferation, cell cycle and apoptosis, and PTPase specific inhibitor Na(3)VO(4) could induce Raji cell growth inhibition, G(2)/M arrest and apoptosis via down-regulation of Bcl-2 and cyclin B1, and reduction of mitochondrial transmembrane potential.
Apoptosis ; drug effects ; Cell Division ; drug effects ; Cyclin B ; analysis ; Cyclin B1 ; Enzyme Inhibitors ; pharmacology ; Humans ; Leukocyte Common Antigens ; analysis ; Membrane Potentials ; drug effects ; Mitochondria ; drug effects ; physiology ; Protein Tyrosine Phosphatases ; antagonists & inhibitors ; Vanadates ; pharmacology

OBJECTIVE To explore the inhibitory effects of epalrestat (EPS) on platelet-derived growth factor (PDGF)-induced rat pulmonary artery smooth muscle cells proliferation by inhibiting aldose reductase (AR) expression.METHODS Primary rat pulmonary arterial smooth muscle cells (PASMCs) were prepared from the pulmonary artery of male 10-week-old Sprague-Dawley rats using explant method.PDGF 30 mg·L-1was given to induce cell proliferation.After PASMCs grew to 70%-80% conflu?ence, AR small-interferring RNA(ARsiRNA) was transfected with Lipofectamine 3000 into PASMCs. After 24 h,the expression and activity of AR were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR),Western blotting and spectrophotometric method,respectively to investigate EPS on PASMCs proliferation and proliferating cell nuclear antigen (PCNA) and collagenⅠexpression induced by PDGF from in vitro. PASMCs (normal control, PDGF 30 mg·L-1, PDGF+EPS 1, 10 and 100 μmol·L-1,EPS 100 μmol·L-1)were treated according to groups.Cell proliferation was measured by BrdU marking and flow cytometry. The expressions of AR, PCNA and collagenⅠwere analyzed with RT-qPCR and Western blotting.RESULTS In cultured PASMCs,compared with normal control group, the application of exogenous PDGF-induced cell proliferation concomitantly up-regulated AR expres?sion and activity (P<0.01), and such effect was abolished by ARsiRNA. Compared with PDGF group, EPS attenuated PDGF-induced proliferation of PASMCs,expression of PCNA,and collagenⅠ(P<0.05, P<0.01),and the inhibitory effect of EPS was accompanied by inhibition of AR expression(P<0.05,P<0.01).CONCLUSION EPS inhibits PDGF-induced proliferation of PASMCs via inhibiting AR expression.

Praeruptorin C (PC), D (PD) and E (PE) are important compounds extracted from Peucedanum praeruptorum DUNN and have been reported to exert multiple pharmacological activities. The present study is purposed to determine the inhibition of PC, PD and PE on the activity of important phase I metabolic enzymes-carboxylesterases (CES). In vitro human liver microsomes (HLM) incubation system was used to determine the inhibition potential of PC, PD and PE on the activity of CES1 and CES2. Inhibition behaviour was determined, and in vitro-in vivo extrapolation was performed by using the combination of in vitro inhibition kinetic parameter (K_i) and in vivo exposure level of PD. PD exhibited the strongest inhibition on the activity of CES1, with 81.7% activity inhibited by 100 μmol·L^-1 of PD. PD noncompetitively inhibited the activity of CES1 with the K_i to be 122.2 μmol·L^-1, indicating inhibition potential of PD towards CES1 in vivo. Therefore, closely monitoring the endogenous metabolic disorders caused by PD and interaction between PD and drugs mainly undergoing CES1-catalyzed metabolism is very necessary.

OBJECTIVETo identify a novel HLA allele DRB1 * 16:36 from a Uygur woman.

METHODSPCR-SBT technology was applied to the extracted DNA for genotyping, and a possible new gene was sequenced by using sequence specific primers and single stranded SBT. This novel allele was compared with known most homologous gene sequences and their difference was analyzed.

RESULTSThis novel allele was different from HLA alle DRB1 * 16:23, and had highest similarity in 2 nucleotides at position 227 A→T and 236 T→C in exon 2, resulting in 3 amino acid changes from Tyr to Phe at codon 47 and Val to Ala at codon 50. The sequence of this novel allele had been submitted to GenBank.

CONCLUSIONThis HLA allele DRB1 * 16:23 has been confirmed to be a novel allele, and has been officially named DRB1 * 16:36 by the World Health Organization (WHO) Nomenclature Committee in May 2015.

Alleles ; Base Sequence ; DNA Primers ; Exons ; Female ; Genotype ; HLA-DRB1 Chains ; genetics ; Humans ; Polymerase Chain Reaction ; Sequence Analysis, DNA

【Objective】To investigate whether oral administration of probiotics could improve the aluminum-induced hippocampal inflammation in mice.【Methods】Twenty-four 8-week-old male C57BL/6 mice were randomly divided into 4 groups，6 in each. The mice in control（CON）group，AlCl3-treated（Al）group，probiotics-treated（PO）group and treatment-combined（Al+PO）group were treated with sterile water，oral AlCl3，probiotics in sterile water and a combination of oral AlCl3 and probiotics in sterile water ，respectively. After six weeks of treatment，immunofluorescence staining was used to test the numbers of activated microglia（Iba-1+/CD68+ cells） and the expression level of brain-derived neurotrophic factor（BDNF）in hippocampus；enzyme linked immunosorbent assay（ELISA）was employed to determine the levels of interleukin- 1 β（IL- 1 β） and tumor necrosis factor- α（TNF- α）in serum and hippocampus.【Results】 The morphology revealed that compared with those in CON group，in Al group，the numbers of Iba-1+/CD68+ cells increased significantly（P < 0.01）and the BDNF level decreased significantly（P < 0.01）. Compared those in Al group ， in Al+PO group ，the numbers of Iba-1+/CD68+ cells were significantly lower（P < 0.01）and the BDNF level significantly higher（P < 0.01）. ELISA results showed that compared with those in CON group，in Al group，the levels of IL-1β and TNF- α in serum and hippocampus had a significant rise（P < 0.01）. Compared those in Al group，in Al+PO group，the levels of IL- 1 β in serum and hippocampus and TNF-α in hippocampus had a significant reduction （P < 0.01）.【Conclusions】Oral probiotics improves the aluminum-induced hippocampal inflammation in mice.

To investigate whether the protection of rutaecarpine against bleomycin-induced pulmonary fibrosis is mediated by inhibiting Notch1/eukaryotic initiation factor 3a (eIF3a) signaling pathway, and whether these effects are related to the synthesis and release of calcitonin gene-related peptide (CGRP) and inhibition of epithelial-mesenchymal transition (EMT) of alveolar epithelial cells, male Sprague-Dawley rats were randomly divided into five groups (=12), respectively, Control group, bleomycin group, rutaecarpine (100, 300 mg·kg⁻¹) group and capsaicin plus rutaecarpine (300 mg·kg⁻¹) group. Bleomycin (5 mg·kg⁻¹) was used to induce pulmonary fibrosis rat model. Rats were given capsaicin (50 mg·kg⁻¹) by subcutaneous injections 1 days before and 7, 14, 21 days after induce pulmonary fibrosis rat model to deplete endogenous CGRP. At the end of experiments, blood was collected from carotid artery to determinate the plasma levels of CGRP by ELISA. Pulmonary tissue change was observed by HE staining. Masson's trichrome stain was used to demonstration collagen deposition. The collagen I expression in pulmonary tissue was measured by immunohistochemisty. The expression of CGRP, Notch1, eIF3a, collagen I, vimentin, alpha-smooth muscle actin (α-SMA), E-cadherin and zonula occludens-1 (ZO-1) was detected by qPCR or Western blot. Compared with the control group, the pulmonary tissue of the bleomycin group showed significant fibrosis, including significant disturbed alveolar structure, marked thickening of the interalveolar septa and dense interstitial infiltration by inflammatory cells and fibroblasts, and concomitantly with the decrease in plasma CGRP and expression of CGRP. Importantly the expression of E-cadherin and ZO-1 was decreased and expression of Notch1, eIF3a, collagen I, vimentin and α-SMA was increased in bleomycin group (<0.05 or <0.01). Compared with the bleomycin group, rutaecarpine (100, 300 mg·kg⁻¹) group significantly reduced bleomycin-induced pulmonary injury concomitantly with the increase in plasma CGRP and expression of CGRP. Importantly the expression of E-cadherin and ZO-1 was increased and expression of Notch1, eIF3a, collagen I, vimentin and α-SMA was decreased by rutaecarpine treatment (<0.05 or <0.01). All these effects of rutaecarpine were abolished by capsaicin.These results suggest that rutaecarpine protects against bleomycin-induced pulmonary fibrosis by inhibiting Notch1/eIF3a signaling pathway, alleviating EMT process, which is related to the increased synthesis and release of CGRP.