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1.
Inflammopharmacology ; 27(3): 511-520, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30911862

ABSTRACT

OBJECTIVE: To investigate whether glucocorticoids, the hallmark medication for systemic lupus erythematosus (SLE), could prevent the development of neuropsychiatric SLE (NPSLE). METHODS: The protective effects of prednisone on NPSLE were tested using the open field, object recognition/placement, forced swim, tail suspension, and sucrose preference tests in MRL/lpr mice. Auto-antibody titres and the weight of lymph nodes were also measured. RESULTS: MRL/lpr mice exhibited mild depression at the age of 8 weeks before progressing with spatial cognitive impairment and severe depression-like behaviour at the age of 16 weeks. Treating MRL/lpr mice with prednisone (5 mg/kg) from the age of 8 weeks decreased anti-cardiolipin and anti-N-methyl-D-aspartate (NMDA) receptor antibody titres in the brain, reduced the weight of lymph nodes, and prolonged the floating latency in the forced swim test. However, prednisone (3 or 5 mg/kg) had no preventive effect on the development of spatial cognitive impairment and other depression-like behaviours in MRL/lpr mice. The dose of prednisone had a positive correlation with the floating latency in the forced swim test, while it offered no effects on all other behavioural tests. CONCLUSION: Our results provide evidence that early treatment with prednisone had a limited effect on the development of neuropsychiatric symptoms in MRL/lpr mice. Further work is needed in other models beyond NPSLE in MRL/lpr mice before any definitive conclusions are made on the efficacy of prednisone in human NPSLE.


Subject(s)
Lupus Vasculitis, Central Nervous System/drug therapy , Prednisone/pharmacology , Animals , Brain/drug effects , Brain/metabolism , Cardiolipins/metabolism , Depression/metabolism , Disease Models, Animal , Female , Glucocorticoids/pharmacology , Lupus Vasculitis, Central Nervous System/metabolism , Lymph Nodes/metabolism , Mice , Mice, Inbred MRL lpr , Protective Agents/pharmacology , Receptors, N-Methyl-D-Aspartate/metabolism
3.
4.
Front Plant Sci ; 8: 1069, 2017.
Article in English | MEDLINE | ID: mdl-28676814

ABSTRACT

The import of sugar from source leaves and it further accumulation in grape berries are considerably high during ripening, and this process is mediated via sucrose transporters. In this study, a grape sucrose transporter (SUT) gene, VvSUC27, located at the plasma membrane, was transferred to tobacco (Nicotiana tabacum). The transformants were more sensitive to sucrose and showed more rapid development, especially roots, when cultured on MS agar medium containing sucrose, considering that the shoot/root dry weight ratio was only half that of the control. Moreover, all transformed plants exhibited light-colored leaves throughout their development, which indicated chlorosis and an associated reduction in photosynthesis. The total sugar content in the roots and stems of transformants was higher than that in control plants. No significant difference was observed in the leaves between the transformants and control plants. The levels of growth-promoting hormones were increased, and those of stress-mediating hormones were reduced in transgenic tobacco plants. The qRT-PCR analysis revealed that the expression of VvSUC27 was 1,000 times higher than that of the autologous tobacco sucrose transporter, which suggested that the markedly increased growth rate of transformants was because of the heterogeneously expressed gene. The transgenic tobacco plants showed resistance to abiotic stresses. Strikingly, the overexpression of VvSUC27 leaded to the up regulation of most reactive oxygen species scavengers and abscisic acid-related genes that might enable transgenic plants to overcome abiotic stress. Taken together, these results revealed an important role of VvSUC27 in plant growth and response to abiotic stresses, especially in the presence of sucrose in vitro.

5.
Life Sci ; 171: 45-50, 2017 Feb 15.
Article in English | MEDLINE | ID: mdl-28088452

ABSTRACT

AIMS: Extracts of Tripterygium wilfordii Hook F (TwHF), a traditional Chinese herbal medicine, have been widely used for treating rheumatoid arthritis (RA) in combination with methotrexate (MTX) in China for several decades. However, the efficacy and safety of MTX plus TwHF treatment remain unclear. MAIN METHODS: A comprehensive search of databases in both Chinese and English was performed. Data from the selected studies were extracted and analyzed independently by two authors. KEY FINDINGS: Six randomized controlled trials were included in the final analysis with a total of 643 patients. All trials added TwHF (in the form of Tripterygium glycosides) to the MTX-based therapy. For efficacy, the addition of TwHF increased 50% responder rates (RR) (RR 1.337, 95% confidence interval [CI]: 1.188-1.505, P<0.001), and it reduced swollen and tender joint counts, shortened the duration of morning stiffness, decreased the erythrocyte sedimentation rate, and decreased the level of C-reactive protein and rheumatoid factor. For safety, the addition of TwHF did not increase the rate of adverse events (RR 0.824, 95% CI: 0.635-1.068, P=0.143). SIGNIFICANCE: MTX plus TwHF therapy may be a more effective and similar safe strategy for treating RA compared to MTX monotherapy. Further large clinical trials to investigate the TwHF add-on therapy are warranted.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Methotrexate/therapeutic use , Plant Extracts/therapeutic use , Tripterygium/chemistry , Drug Therapy, Combination , Humans , Randomized Controlled Trials as Topic
6.
Neuroscience ; 328: 22-9, 2016 07 22.
Article in English | MEDLINE | ID: mdl-27133574

ABSTRACT

Proinflammatory cytokine interleukin-1 beta (IL-1ß) may accumulate in the brain during status epilepticus, but whether it contributes to the progressive refractoriness of SE remains unclear. By using a kainic acid-induced SE mice model, we tested whether pharmacological blockade or knock-out of interleukin-1 receptor type 1 (IL-1R1) could influence the diazepam-refractory phenomenon of prolonged SE. We confirmed diazepam failed to terminate prolonged SE (allowed to continue for 40min before diazepam administration). The expression level of IL-1ß in the hippocampus during prolonged SE was significantly higher than that of baseline. Interestingly, prolonged SE was not diazepam-refractory in IL-1R1 knock-out mice. Moreover, administration of interleukin-1 receptor antagonist (IL-1RA) combined with diazepam terminated established prolonged SE, while IL-1RA alone is not capable to terminate prolonged SE. On the contrary, administration of recombinant human IL-1ß weakens the efficacy of diazepam by prolonging its latency to terminate non-prolonged SE. Thus, the present study provides direct evidence that accumulated IL-1ß contributed to the diazepam refractoriness of prolonged SE, and suggests that interleukin-1 receptor is a target for adjunctive control of diazepam-refractory SE.


Subject(s)
Anticonvulsants/pharmacology , Diazepam/pharmacology , Drug Resistant Epilepsy/drug therapy , Receptors, Interleukin-1 Type I/antagonists & inhibitors , Receptors, Interleukin-1 Type I/metabolism , Status Epilepticus/drug therapy , Animals , Disease Models, Animal , Drug Resistant Epilepsy/metabolism , Drug Resistant Epilepsy/pathology , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology , Interleukin-1beta/metabolism , Interleukin-1beta/pharmacology , Kainic Acid , Mice, Inbred C57BL , Mice, Knockout , Random Allocation , Receptors, Interleukin-1 Type I/genetics , Recombinant Proteins/pharmacology , Status Epilepticus/metabolism , Status Epilepticus/pathology
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