ABSTRACT
Objective:To investigate the effects of arsenic trioxide combined with dihydroartemisinin on proliferation, cell cycle, and apoptosis of THP-1 cells, and explore the mechanism. Method:The thiazolyl blue （MTT） method was applied to detect the effect of different concentrations of arsenic trioxide, dihydroartemisinin and arsenic trioxide combined with dihydroartemisinin on the proliferation of THP-1 cells. Annexin V/propidium iodide（PI）assay was used to detect the change of THP-1 cell cycle and apoptosis．Western blot was performed to assess the expression of cysteine protease-3（Caspase-3）, cleaved Caspase-3, B-lymphocytoma-2（Bcl-2） and Bcl-2 associated X protein （Bax）. The changes of cell morphology were observed under high intension microscope. Result:Compared with blank group, arsenic trioxide and dihydroartemisinin both exhibited obvious antiproliferative effect on the human acute monocytic leukemia cell line THP-1 in time-dose dependence （P<0.01）. After 48 h, compared with the same dose of arsenic trioxide or that of dihydroartemisinin alone, the inhibition effect of 1 µmol·L-1 arsenic trioxide combined with 2 µmol·L-1 dihydroartemisinin on proliferation of THP-1 cells was significantly stronger （P<0.01）. Compared with the control group, arsenic trioxide combined with dihydroartemisinin significantly arrested the cells in G1 phase （P<0.01）, induced the downregulation of Caspase-3 and Bcl-2 （P<0.01） and upregulation of cleaved Caspase-3 significantly（P<0.05）. Conclusion:Arsenic trioxide combined with dihydroartemisinin can significantly inhibit the proliferation and induce apoptosis of THP-1 cells. The possible mechanism may be related to arrest the cells in G1 phase, reduce the expression of Caspase-3 and Bcl-2, increase the expression of cleaved Caspase-3.
ABSTRACT
Toll-like receptors 4(TLR4),an important member of the TLR family,is considered as gene encoding LPS recep?tors,and major receptors for identifying lipopolysaccharide(LPS).LPS-induced TLR4 signaling pathway plays a key role in endotox?emia.After TLR4 activated by LPS,the mitogen-activated protein kinase(MAPK)signaling pathway and nuclear transcription factor κB(NF-κB)are activated and large amounts of inflammatory factors are released,triggering inflammatory cascade reaction.This arti?cle reviews the mechanisms of endotoxemia in treatment based on TLR4 signal pathway in three perspectives:the effects of LPS-TLR4 signaling pathway on the upstream target proteins,LPS-induced TLR4 signal transduction,and the downstream target proteins regulat?ed by LPS-TLR4 signaling pathway.
ABSTRACT
Alzheimer's disease(AD),the most common form of dementia,it is lack of effective cure or preventive treatment.Dementias in the elder are an increasing medical,social and economic problems and current treatments are only mildly effective.Recently,amyloid-beta protein(A?) has become a major therapeutic target.A? vaccine treatment can improve cognition in the patients with AD,but adverse events,such as meningencephalitis were observed in clinical study.The passive A? immunotherapy in humans is effective with possible safety.However,patients need to be monitored carefully.
ABSTRACT
Objective To investigate the effects of different doses of pituitary adenylate cyclase- activating polypeptide(PACAP)on the functional and morphological outcome in a mice model of Parkinson' s disease(PD)rendered by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Methods Male mice were treated with PACAP 0.02, 0.20 or 2.00 ?g by iv bolus for 7 days after MPTP was administered, and were compared with the saline-treated mice.The immunohistochemistry and Western blot were used to detect the alterations of PD biomarker including tyrosine hydroxylase(TH), dopamine transporter(DAT)and vesicular monoamine transporter2(VAMT2).In addition, monoamine neurotransmitters in the striatum of mice were measured by the high performance liquid chromatography (HPLC).Results TH immunohistochemistry indicated that the number of TH-positive neurons in the substantia nigra was increased in all PACAP-treated mice(PACAP(0.02 ?g/d)group was 93.33?4.87, F=85.85,P