الملخص
This study aimed to investigate the effects of Erxian Decoction(EXD)-containing serum on the proliferation and osteogenic differentiation of MC3T3-E1 cells under oxidative stress through BK channels. The oxidative stress model was induced in MC3T3-E1 cells by H_2O_2, and 3 mmol·L~(-1) tetraethylammonium(TEA) chloride was used to block the BK channels in MC3T3-E1 cells. MC3T3-E1 cells were divided into a control group, a model group, an EXD group, a TEA group, and a TEA+EXD group. After MC3T3-E1 cells were treated with corresponding drugs for 2 days, 700 μmol·L~(-1) H_2O_2 was added for treatment for another 2 hours. CCK-8 assay was used to detect cell proliferation activity. The alkaline phosphatase(ALP) assay kit was used to detect the ALP activity of cells. Western blot and real-time fluorescence-based quantitative PCR(RT-qPCR) were used to detect protein and mRNA expression, respectively. Alizarin red staining was used to detect the mineralization area of osteoblasts. The results showed that compared with the control group, the model group showed significantly blunted cell proliferation activity and ALP activity, reduced expression of BK channel α subunit(BKα), collagen Ⅰ(COL1), bone morphogenetic protein 2(BMP2), osteoprotegerin(OPG), and phosphorylated Akt, decreased mRNA expression levels of Runt-related transcription factor 2(RUNX2), BMP2, and OPG, and declining area of calcium nodules. EXD-containing serum could significantly potentiate the cell proliferation activity and ALP activity, up-regulate the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt, and forkhead box protein O1(FoxO1), promote the mRNA expression of RUNX2, BMP2, and OPG, and enlarge the area of calcium nodules. However, BK channel blockage by TEA reversed the effects of EXD-containing serum in promoting the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt and FoxO1, increasing the mRNA expression of RUNX2, BMP2, and OPG, and enlarging the area of calcium nodules. EXD-containing serum could improve the proliferation activity, osteogenic differentiation, and mineralization ability of MC3T3-E1 cells under oxidative stress, which might be related to the regulation of BK channels and downstream Akt/FoxO1 signaling pathway.
الموضوعات
Osteogenesis , Core Binding Factor Alpha 1 Subunit/pharmacology , Large-Conductance Calcium-Activated Potassium Channels/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Calcium/metabolism , Cell Differentiation , RNA, Messenger/metabolism , Cell Proliferation , Osteoblastsالملخص
<p><b>BACKGROUND</b>Depression related cognitive deficits are frequently considered as simple epiphenomena of the disorder. However, whether or not the depression might directly bring about cognitive deficits is still under investigation. This study was to investigate the distinct pattern of cognitive deficits in patients with depression by comparing the cognitive function before and after anti-depressive drug therapy.</p><p><b>METHODS</b>Sixty cases of patients, first-time diagnosed with depression, were assessed by 17-item Hamilton Rating Scale for Depression (HAMD17scale). The memory ability was tested by quantitatively clinical memory scale, while the attention ability by modified Ruff 2&7 Selective Attention Test. Forty-two healthy volunteers were recruited as controls. The depressive patients were treated with Venlafaxine (75 - 300 mg/d), Fluoxetine (20 - 40 mg/d), Paroxetine (20 - 40 mg/d), and Sertraline (50 - 150 mg/d). After 12 weeks treatment, patients were tested again by HAMD17scale, quantitatively clinical memory scale, and modified Ruff 2&7 selective attention test to assess the effect of anti-depressive drugs on cognitive deficits.</p><p><b>RESULTS</b>The memory quotient (MQ) was significantly lowered in depressive patients. The selection speed was also significantly decreased and the number of missing and error hits increased in the depression group as compared to control. However, there was no significant difference in clinical memory scale and Ruff 2&7 selective attention test between mild-to-moderate and severe depression group. Importantly, after anti-depressive drug therapy, the HAMD17 scale scores in depressive patients were significantly decreased, but the MQ, directional memory (DM), free recall (FR), associative learning (AL), and face recognition were comparable with those before the treatment. Furthermore, the selection speed and the number of missing and error hits were also not significantly different after anti-depressive drugs treatment.</p><p><b>CONCLUSIONS</b>Depressive patients suffer from short-term memory deficits, and attention extent, stability and rearrangement deficiency. Even though anti-depressive drugs sufficiently relieve the cardinal presentation of depression, they could not successfully alleviate the accompanying cognitive deficits. This might indicate a distinct pattern of cognitive deficits in patients with depression.</p>
الموضوعات
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Antidepressive Agents , Therapeutic Uses , Cognition Disorders , Depression , Drug Therapy , Memory , Physiology , Neuropsychological Testsالملخص
Objective To investigate the effect of glucocorticoids of different dosages on mortality and hippocampal neuron apoptosis in rats after traumatic brain injury (TBI).Methods All the adult male Wistar rats were allocated into normal control group,dexamethasone (DXM) treatment group,methylprednisolone (MP) treatment group,injury control group,low-dose DXM treatment group,moderate-dose DXM treatment group,high-dose DXM treatment group,low-dose MP treatment group,moderate-dose MP treatment group,and high-dose MP treatment group (n=22).Rats in the later seven groups (the injuried groups) accepted fluid percussion injury to induce TBI models,and then,treatments were given.The injury severity was evaluated with modified Neurological Severity Scale 24 h after injury.The number ofhippocampal neuron apoptosis was examined using TUNEL after 24 and 48 h,and 7 and 14 d of injury.The mortality of rats in each group was also observed during a 14-day-follow-up period.The changes of brains,pituitaries,hearts and lungs in the dead rats were examined by H.E.staining.Results No significant difference on the scores of modified Neurological Severity Scale was noted in the injuried groups 24 h after the injury (P>0.05).The hippocampal neuron apoptosis began to appear 24 h after inju~,peaked at 48 h,and declined in 7 to 14 d.At 48 h after injury,the number of hippocampal neuron apoptosis in high-dose DXM treatment and high-dose MP treatment groups was significantly higher than that in the injury control group (P<0.05).The mortality of rats in high-dose DXM treatment and high-dose MP treatment was significantly higher than that in the injury control group (P<0.05).The autopsy of dead rats in each group revealed various degrees of interstitial pneumonia and hypophysial congestion in rats receiving high-dose glucocorticoids.Conclusion TBI could induce hippocampal neuron apoptosis,and early administration of high-dose glucocorticoids aggravates the apoptosis and increases the mortality,for which interstitial pneumonia and hypophysial congestion would account.