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1.
Acta Pharmaceutica Sinica ; (12): 1621-1629, 2022.
Article in Chinese | WPRIM | ID: wpr-929457

ABSTRACT

Cystine/glutamate antiporter [system Xc(-)] is a sodium independent amino acid transporter, which is a heterodimer composed of light chain subunit xCT and heavy chain subunit 4F2hc (CD98) through covalent disulfide bond. System Xc(-) typically mediates cystine uptake and glutamate output, helps to maintain the balance of glutamate, cystine and cysteine inside and outside the cell, regulates the level of glutamate inside and outside the membrane and the synthesis of intracellular glutathione, thus affecting oxidative stress and glutamate neurotoxicity. This review expounds the structure and function of system Xc(-), analyzes the role of the transporter in physiology and pathology, discusses the role and mechanism in different diseases, and discusses the specific research progress of system Xc(-) as a drug target. This review summarizes the research status of system Xc(-) and provides theoretical guidance for further research on system Xc(-) and drug discovery.

2.
Biomedical and Environmental Sciences ; (12): 952-962, 2021.
Article in English | WPRIM | ID: wpr-921353

ABSTRACT

Objective@#To our knowledge, no definitive conclusion has been reached regarding the relationship between glucocorticoids and hypertension. Here, we aimed to explore the characteristics of glucocorticoids in participants with dysglycemia and hypertension, and to analyze their association with blood pressure indicators.@*Methods@#The participants of this study were from the Henan Rural Cohort study. A total of 1,688 patients 18-79 years of age were included in the matched case control study after application of the inclusion and exclusion criteria. Statistical methods were used to analyze the association between glucocorticoids and various indices of blood pressure, through approaches such as logistic regression analysis, trend tests, linear regression, and restricted cubic regression.@*Results@#The study population consisted of 552 patients with dysglycemia and hypertension (32.7%). The patients with co-morbidities had higher levels of serum cortisol ( @*Conclusions@#Serum deoxycortisol was positively correlated with systolic blood pressure, pulse pressure, mean arterial pressure, mean blood pressure, and mean proportional arterial pressure. Glucocorticoids (deoxycortisol and cortisol) increase the risk of hypertension in people with dysglycemia, particularly in those with T2DM.


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Blood Pressure , Case-Control Studies , China/epidemiology , Cohort Studies , Glucocorticoids/blood , Glycemic Load , Hydrocortisone/blood , Hypertension/etiology , Prevalence , Risk Factors , Rural Population
3.
Journal of Experimental Hematology ; (6): 1224-1230, 2021.
Article in Chinese | WPRIM | ID: wpr-888542

ABSTRACT

OBJECTIVE@#To analyze the proliferation potential of bone marrow-derived mesenchymal stem cells (MSC) in patients with myelodysplastic syndrome (MDS).@*METHODS@#The MSC derived from the 24 patients with newly diagnosed MDS (MDS-MSC group) and MSC derived from 15 patients with nutritional anemia (control group) in the Affiliated Hospital of Hebei University were used as the research objects. The proliferation potential of MSC was analyzed by colony-forming unit assay, doubling time, cumulative passaging, cell number after 10 days of culture with equal amount of MSC and MTT experiment. The mechanism of abnormal proliferation was analyzed by cell cycle experiment, apoptosis experiment and p21 gene expression assay.@*RESULTS@#In the colony forming unit assay, the number of MDS-MSC colonies was 4.44±2.51, which was significantly lower than that of the control group (12.44±2.55)(P<0.01); the doubling time of MDS-MSC group was significantly longer than that of the control group (7.80±3.26 vs 3.63±0.85) (P<0.01); the number of MDS-MSC in 5×10@*CONCLUSION@#The proliferative capability of MDS-MSC is significantly reduced, which relates with the arrest of cell cycle in G


Subject(s)
Humans , Apoptosis , Bone Marrow Cells , Cell Proliferation , Mesenchymal Stem Cells , Myelodysplastic Syndromes
4.
Journal of Experimental Hematology ; (6): 1002-1006, 2021.
Article in Chinese | WPRIM | ID: wpr-880183

ABSTRACT

Emerging data have demonstrated that bone marrow mesenchymal stem cells (MSCs) play important roles in the progression of myelodysplastic syndrome (MDS). Experiments in vitro have showed that MSCs derived from MDS patients (MDS-MSC) exhibit the biological characteristics of cell senescence. Although the underlying mechanisms that regulate cell senescence need to be further elucidated, existing researches indicate that the mechanisms of MDS-MSC senescence have significant heterogeneity. Depth understanding of the underlying mechanisms involved in cell senescence of MDS-MSC are crucial to explore the potential therapeutic target of MDS. Therefore, this review summarizes research advances related with MSC senescence, such as MDS-MSC intrinsic changes in telomere shortening, DNA methylation status, oxidative stress and signal pathways regulating cell senescence in recent years.


Subject(s)
Humans , Bone Marrow , Bone Marrow Cells , Cellular Senescence , Mesenchymal Stem Cells , Myelodysplastic Syndromes
5.
Journal of Experimental Hematology ; (6): 1561-1567, 2019.
Article in Chinese | WPRIM | ID: wpr-775685

ABSTRACT

OBJECTIVE@#To investigate the phenotype and molecular mechanism of DCA on MDS cell model, and to study the response of chemotherapeutic medicines to MDS cells through multiple dimensions, such as cell proliferation, invasion, migration and apoptosis, thus revealing the molecular mechanism of DCA treatment of MDS and its relationship with SHP-1 gene methylation.@*METHODS@#MTT assay was used to determine the survival rate of MDS cells after treated by different concentrations of DCA. The effect of DCA on the invasion and migration of MDS cells was detected by Transwell assay method. Apoplexin V-FITCPI was used to detect apoptosis, the MDS treatment on the mechanism of DCA was investigated by Western blot and Real-time PCR experiment.@*RESULTS@#According to the experiment, it was found that tumor proliferation could be inhibited when MDS skm-1 cells was treated by DCA, and the absorbance was lower and the inhibitory effect was more obvious in the 2.0, 5.0 μmol/L DCA group than in the 0.5 μmol/L DCA group and the negative control group. Compared with the control group, the number of MDS skm-1 cells crossing through the transwell upper chamber was significantly decreased after DCA application. After treated with 0.5, 2.0 and 5.0 μmol/L DCA, the apoptosis rate of MDS cells was 4.54%, 9.31% and 16.58% respectively, while the apoptosis rate of the control group was 3.20%, which shows the apoptosis rate increased significantly with the concentration of DCA. After treatment of MDS cell lines with different concentration of DCA, the methylation status of SHP-1 gene was decreased with the increase of drug concentration, the expression of SHP-1 was increased, the expression of STAT3 was decreased and the level of phosphorylation was decreased.@*CONCLUSION@#By analyzing the phenotypic response of DCA treatment on MDS cells, it was found that interfere with MDS can be performed by inhibiting proliferation, metastasis, and inducing apoptosis in a dose-dependent way. It revealed that the molecular mechanism by DCA treatment can improve the methylation of SHP-1 gene and inhibit the expression of p-STAT3.


Subject(s)
Humans , Apoptosis , Cell Line , Cell Line, Tumor , Cell Proliferation , Decitabine , Protein Tyrosine Phosphatase, Non-Receptor Type 6
6.
Medical Journal of Chinese People's Liberation Army ; (12): 239-243, 2018.
Article in Chinese | WPRIM | ID: wpr-694106

ABSTRACT

Objective To investigate the relations of absolute lymphocyte counts (ALC) to the therapeutic responses in patients with myelodysplastic syndrome (MDS) after the first course of decitabine (DAC) treatment.Methods Clinical data of 35 patients with MDS and MDS-derived secondary acute myeloid leukemia (AML) who were admitted in the Affiliated Hospital of Hebei University from Jan.2014 to Dec.2016 and treated with DAC were included in the present study.The patients were grouped into high lymphocyte group (H-Lym,ALC ≥ 1.2 × 109/L) and low lymphocyte group (L-Lym,ALC<1.2 × 109/L) based on the ALC in days 28-35 after the first course of DAC treatment.The baseline data of both groups were compared with Pearson x2 analysis,while t test was used to analyze the changes of lymphocyte number before and after the first course of DAC treatment.Progressionfree survival (PFS) was estimated with Kaplan-Meier method,and the cumulative survival (CS) was compared between the two groups using log-rank test.Results Of the 35 patients,15 were in H-Lym group and 20 in L-Lym group.No significant difference existed in the baseline lymphocyte levels between the two groups (P>0.05).The statistically significant differences (P<0.05) existed only in the patients of the two groups who were with the proportion of bone marrow blasts ≥ 10%.The ALC in H-Lym group were slightly higher after the first course of DAC treatment than that at the time of diagnosis,but with no statistically significant (P>0.05).However,the ALC in L-Lym group were significantly lower after the first course of DAC treatment than that at the time of diagnosis (P<0.05).Patients had higher overall response rate (ORR) in H-Lym group than in L-Lym group (80% vs.40%,P<0.05).The median PFS was 10 months in H-Lym group and 7.6 months in L-Lym group (P<0.05).Univariate analysis showed that the low ALC was a poor prognostic factor for the progression ofMDS (P<0.05).Conclusion Patients with ALC ≥ 1.2 × 109/L after the first course of DAC treatment will have better ORR and longer PFS.

7.
Basic & Clinical Medicine ; (12): 255-259, 2018.
Article in Chinese | WPRIM | ID: wpr-693881

ABSTRACT

Myelodysplastic syndrome (MDS) is definded as a group of clonal hematological malignancies characterized by bone marrow (BM) ineffective.hematopoiesis and increases risk for progression to acute myeloid leukemia. The altered BM mesenchymal stem cells (MSCs) play a pivotal role in the evolution and propagation of MDS. Com-pared to normal MSCs, MSCs in MDS often exhibit altered Cytogenetic, epigenetic, differentiation and functional properties, moreover, high MSCs density is associated with poor prognostic factors, which translated into a signifi-cantly diminished ability to support normal hematopoiesis, facilitates survival of malignant hematopoietic cells, ulti-mately promote disease progression and transform to acute myeloid leukemia.Therefore, characterization of key steps in the pathogenesis of MDS will lead to new approaches to treat patients with this disease.

8.
Journal of Experimental Hematology ; (6): 1574-1578, 2018.
Article in Chinese | WPRIM | ID: wpr-689894

ABSTRACT

Hypomethylating agents(HMA) currently are widely used in the treatment of myelodysplastic syndromes (MDS), provide a significant improvement in the treatment of MDS. However, resistance to HMA is an almost universal phenomenon. This review was focused on immune effects related to DNA methylation, and to explore the mechanism underlying HMA resistance involved in immune checkpoint pathways. However, the optimal role of checkpoint blockade therapy (CBT) and immune checkpoint pathways remain in HMA failure questionable. The better understanding of immune checkpoint pathways in resistance of HMA offers a compelling rationale to introduce CBT in patients as a novel treatment option. CBT is an established strategy in solid tumors with potential as an adjunctive therapy in hematologic malignancies, therefore, may alter the treatment landscape in MDS. The suitability and effectiveness of combining HMA with CBT need to be confirmed by the results of ongoing clinical trials, so as to find novel strategies to improve outcome after failure of HMA.

9.
Journal of Experimental Hematology ; (6): 942-946, 2018.
Article in Chinese | WPRIM | ID: wpr-689548

ABSTRACT

Myelodysplastic syndromes (MDS) comprise a group of malignant hematopoietic stem cell (HSC) disorders characterized by ineffective hematopoiesis. The risk of transformation to acute myeloid leukemia (AML) is increasing. The initiating event in HSC of MDS leads to a growth advantage and subsequent clonal expansion, that is still poorly understood. Accumulating data indicate that the mesenchymal stem cells(MSCs) in MDS model display aberrant characteristics contributing to disease initiation and transformation into AML. MSC derived from MDS displayed the alteration in genetics, epigenetics and gene expression, which contribute to altered morphology, impaired proliferative and differentiation capacity and perturbed cytokine secretions, thus destroy in their ability to support normal hematopoiesis and contribute to malignant progression. A number of promising agents that target the interactions of the MDS clone with MSC are currently investigated in various phases of clinical trial, that might ultimately result in novel therapeutic strategies, targeting niche cells to attenuate leukemic progression. In this article, the current status of MDS treatment, the characteristics of MDS-MSC senescence and phenotypes, the changes of hematopoietic function sapported by senescent MDS-MSC, the significane of MDS-MSC in MDS prognosis and the MDS-MSC as potential target for treatment of MDS are summarized.


Subject(s)
Humans , Hematopoiesis , Hematopoietic Stem Cells , Leukemia, Myeloid, Acute , Mesenchymal Stem Cells , Myelodysplastic Syndromes
10.
Journal of Experimental Hematology ; (6): 993-998, 2018.
Article in Chinese | WPRIM | ID: wpr-689540

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of absolute lymphocyte count(ALC) before start of the first cycle of consolidation chemotherapy(CC) on the relapse free survival in the patients with acute myeloid leukemia(AML), so as to explore a simple and easy method for predicting AML relapse.</p><p><b>METHODS</b>The clinical data of 132 patients with newly diagnosed AML (all non-acute promyelotic leukemia) from 2011 to 2017 were analyzed retrospectively. The 132 AML patients were treated with standard induction chemotherapy (IC) and consolidation chemotherapy (CC). According to lymphocyte count of patients before start of the first cycle of CC, the AML patients were divided into 2 group: high lymphocyte count group (H-Lym≥1.2×10/L) and low lymphocyte count group (L-Lym<1.2×10/L). The differences in ralapse rate and relapse-free survival between 2 groups were analyzed.</p><p><b>RESULTS</b>Among 132 patients with AML, patients who could be valuated and were elicible for the study accounted for 65 (49.24%). The absolute leukocyte count, age, chromosome karyotypes before IC of patients did not show statistical difference between H-Lym group (40 cases) and L-Lym group (25 cases). Unvarvate analysis showed that the Low lymphocyte count and unfavorable chromosome karyotypes were poor prognostic factors for the relapse-free survival time, and there was significant difference between 2 groups (P<0.01). The relapse risk in patients of L-Lym group increased, the hazard ratio (HR)=3.01 (95% CI=1.55-4.98) (P<0.01). In multivariate analysis containing unfavorable prognostic karyotypes, this trend still existed (HR=2.52, 95% CI 1.28-9.98)(P<0.01).</p><p><b>CONCLUSION</b>The AML patients with high lymphocyte count before the first CC have more long relapse free survival time suggesting that the lymphocyte count before the first CC may be prognostic factor for relapse free survival of AML patients.</p>


Subject(s)
Humans , Consolidation Chemotherapy , Leukemia, Myeloid, Acute , Lymphocyte Count , Prognosis , Recurrence , Retrospective Studies
11.
Journal of Experimental Hematology ; (6): 1248-1252, 2018.
Article in Chinese | WPRIM | ID: wpr-689496

ABSTRACT

The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal myeloid disorders characterized by ineffective hematopoiesis and increased risk of transformation to acute myelogenous leukemia (AML). The treatment of MDS is highly dependent on the reliability of the prognostic evaluation model. Current clinical prognostic scoring systems are comprised of morphology, pivotal clinical trials and cytogenetic findings. However, none of the available prognostic systems incorporates disease-related molecular abnormalities, such as somatic mutations. Cumulative evidence suggests that genomic data can also be used clinically to assist the diagnosis, prognosis, prediction of response to specific therapies, and the development of novel and accurate targeted therapies. Therefore, it is not possible to predict the response of patients to molecular targeted drugs, such as demethylation drugs. With the recent advance in whole- genome sequencing technologies, cumulative evidence suggests that genomic data can also be associated with the genesis, prognosis, prediction of response to specific therapies, and the development of novel accuvate targeted therapies, the issue of having some mechanism to dissect this heterogeneity and precision treatment is coming to the fore. However, there are still several hindrances to its clinical application. If these problems can be solved, molecular genetics will further provide a theoretical basis for the application of precision medicine in MDS.


Subject(s)
Humans , Genomics , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Prognosis , Reproducibility of Results
12.
Journal of Experimental Hematology ; (6): 1719-1725, 2018.
Article in Chinese | WPRIM | ID: wpr-773030

ABSTRACT

OBJECTIVE@#To investigate a reliable clinical indication for predicting the therapeutic response of decitabine therapy in the patients with myelodysplastic syndromes (MDS).@*METHODS@#The clinical efficacy of decitabine for 55 cases of MDS was analyzed retrospectively. According to the lymphocyte level at d28 after the first time treatment with decitabine, the patients were divided into high lymphocyte level group (H-Lym≥1.2×10/L) and low lymphocyte level group (L-Lym<1.2×10/L), and the overall response rate (ORR) and the progression-free survival (PFS) time in 2 groups were compared.@*RESULTS@#As compared with L-Lym group, the ORR and PFS time in H-Lym group were significantly enhanced [(76.0% vs 50.0%) (P<0.05) and median time (15.7 months vs 8.5 months)(P<0.05), respectively];the ratio of platelet level ≥100×10/L in H-Lym group was very significantly higher than that in L-Lym group (72.0% vs 20.0%)(P<0.01). Multivariat analysis showed that the risk of disease progression in L-Lym group was 4.45-fold of H-Lym group (95% CI:1.58-12.59)(P<0.05).@*CONCLUSION@#The patients with lymphocyte level ≥1.2×10/L at day 28 after the first time treatment with decitabine show the higher ORR and longer PFS time, therefore. the lymphocyte level at day 28 after first time treatment with decitabine can be used as an early clinical indicator for predecting the response to decitabine treatment.


Subject(s)
Humans , Antimetabolites, Antineoplastic , Decitabine , Lymphocytes , Myelodysplastic Syndromes , Retrospective Studies , Treatment Outcome
13.
China Journal of Chinese Materia Medica ; (24): 4605-4609, 2016.
Article in Chinese | WPRIM | ID: wpr-231014

ABSTRACT

To investigate the chemical compounds from the fruit of Cornus officinalis, six compounds were isolated and determined by extensive spectroscopic analysis as 6'-O-acetyl-7α-O-ethyl morroniside (1), (-)-isolariciresinol 3α-O-β-D-glucopyranoside(2), apigenin (3), cirsiumaldehyde(4), p-coumaric acid (5), caffeic acid (6). Compound 1 was a new iridoid glucoside,and compounds 2-4 were obtained from the Cornus genus for the first time. Compounds 2-6 were evaluated for the viability of PC12 cells when exposed in conditions of oxygen and glucose deprivation. The MTT results showed that compound 4 increased cell viability moderately in OGD/R treated PC12 cells at the concentration of 1.0 μmol•L⁻¹.

14.
Acta Pharmaceutica Sinica ; (12): 1240-1245, 2015.
Article in Chinese | WPRIM | ID: wpr-320095

ABSTRACT

This study was conducted to investigate the paclitaxel loaded by hydrazone bonds in poly(ethylene glycol)-poly(caprolactone) micelles (mPEG-PCL-PTX) on proliferation and apoptosis of human lung cancer A549 cells and its possible mechanisms of anti-tumor activity. The cell proliferation was measured with MTT assay. Flow cytometry were used to analyze the cell cycle. The cell apoptosis was analyzed using Hoechst/P staining. The expression levels of apoptotic genes expression in the mitochondrial apoptosis pathway were detected by RT-PCR and Western blotting, respectively. The mPEG-PCL-PTX could inhibit the proliferation of A549 cells and promote the apoptosis. The Bax, caspase-3 protein expression were increased while Bcl-2 protein expression was decreased in A549 cells. Results showed that the polymer containing hydrazone bond is non-toxic in vitro, the mPEG-PCL-PTX micelles can inhibit the proliferation and induce the apoptosis of A549 cells. Key words: paclitaxel; micelle; A549 cell; proliferation; cell cycle; apoptosis


Subject(s)
Humans , Apoptosis , Caspase 3 , Metabolism , Cell Line, Tumor , Cell Proliferation , Lung Neoplasms , Metabolism , Pathology , Micelles , Paclitaxel , Pharmacology , Polyesters , Polyethylene Glycols , Proto-Oncogene Proteins c-bcl-2 , Metabolism , bcl-2-Associated X Protein , Metabolism
15.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 99-107, 2015.
Article in English | WPRIM | ID: wpr-812167

ABSTRACT

The present study was designed to investigate the antithrombotic effects and underlying mechanisms of the effective components group (ECG) of Xiaoshuantongluo recipe (XECG) and to further verify the rationality and feasibility of ECG-guided methodology in traditional Chinese medicine (TCM) research. The arterial thrombosis model induced by ferric chloride (FeCl3) oxidation and the venous thrombosis model induced by inferior vena cava ligation were established to evaluate the antithrombotic potential of XECG. Our results indicated that XECG significantly prolonged the time to occlusion, activated partial thromboplastin time (APTT), and prothrombin time (PT), and markedly inhibited adenosine diphosphate (ADP)-induced platelet aggregation in the 20% FeCl3-induced arterial thrombosis model. The superoxide dismutase (SOD) activity was significantly increased and the levels of malondialdehyde (MDA) and nitric oxide (NO) were dramatically decreased in the plasma of arterial thrombosis rats after XECG treatment for 12 days. Furthermore, XECG markedly reduced the weight of thrombus formed by inferior vena cava ligation. Additionally, XECG exhibited 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity and protective effect on mitochondrial lipid peroxidation. In summary, XECG played an important role in the prevention of thrombosis through interacting with multiple targets, including inhibition of platelet aggregation and coagulation and repression of oxidative stress. The ECG-guided methodology was validated as a feasible tool in TCM research.


Subject(s)
Animals , Humans , Male , Rats , Drugs, Chinese Herbal , Fibrinolytic Agents , In Vitro Techniques , Malondialdehyde , Metabolism , Nitric Oxide , Metabolism , Platelet Aggregation , Prothrombin Time , Superoxide Dismutase , Metabolism , Thrombosis , Drug Therapy , Metabolism
16.
Journal of Experimental Hematology ; (6): 381-385, 2015.
Article in Chinese | WPRIM | ID: wpr-259581

ABSTRACT

<p><b>OBJECTIVE</b>To explore the effects of aptamer-siRNA nucleic acid compound on growth and apoptosis in myeloid leukemia cell line K562.</p><p><b>METHODS</b>the changes of cellular morphology and structure were observed by using fluorescence microscope, laser confocal microscope, JEM-4000EX transmission electron microscopy; MTT assay were performed to evaluate the sensibility of K562 cells to aptamer-siRNA compound, the apoptosis was detected by DNA gel electro-phoresis.</p><p><b>RESULTS</b>The remarkably changes of morphology and structure of K562 cells treated with 200 µmol/L aptamer-siRNA were observed under fluorescence microscopy and electromicroscopy. As compared with control, the aptamer-siRNA compound showed more inhibitory effect on K562 cells and there was significant difference (P<0.05). The MTT assay showed that the IC50 value of aptamer-siRNA compound for K562 cells was 150 µmol/L. According to agarose gel electrophoresis observation, when the aptamer-siRNA compound showed effect on K562 cells, the typical DNA lader could be observed.</p><p><b>CONCLUSION</b>The aptamer-siRNA compound can significantly induce K562 cell apoptosis, and provide reference for gene therapy of patients with chronic myelocytic lenkemia.</p>


Subject(s)
Humans , Apoptosis , Cell Proliferation , K562 Cells , Leukemia, Myeloid , RNA, Small Interfering
17.
Chinese Journal of Tissue Engineering Research ; (53): 4328-4332, 2015.
Article in Chinese | WPRIM | ID: wpr-461974

ABSTRACT

BACKGROUND:Current research data have shown that patients with epilepsy are often accompanied by complications such as cognitive impairment. Recent studies have demonstrated that melatonin has an inhibitory effect on epilepsy, but its underlying mechanism is unknown. OBJECTIVE: To investigate the effects of melatonin on the cognitive function and GluR2 expression in the hippocampus of rat models of epilepsy, and further study the mechanism of melatonin against epilepsy. METHODS: Rat models of chronic epilepsy were established by intraperitoneal injection of lithium chloride-pilocarpine, and intraperitonealy injected with sufficient amount of physiological saline and melatonin respectively. Control group was set for observation. RESULTS AND CONCLUSION:At 4 and 6 weeks after modeling, the GluR2 expression level in the hippocampus of rats in the epilepsy + melatonin group was significantly higher than that in the epilepsy group (P < 0.05); the GluR2 expression level in the synaptic membrane of hippocampal CA1 region of rats in the control and epilepsy + melatonin groups was significantly higher than that in the epilepsy group (P < 0.05). At 4 days after modeling, compared with epilepsy group and epilepsy + physiological saline group, the escape latency, operation time, active avoidance latency, passive avoidance latency of rats in the epilepsy + melatonin group were significantly decreased (P< 0.05), the correct rate and active avoidance number were significantly increased (P < 0.05). These results demonstrate that melatonin can improve the cognitive function of rat models of epilepsy by up-regulating the expression of GluR2 in the synaptic membrane of hippocampal CA1 region.

18.
China Journal of Chinese Materia Medica ; (24): 721-725, 2014.
Article in Chinese | WPRIM | ID: wpr-300161

ABSTRACT

<p><b>OBJECTIVE</b>To discuss the protective effect of Mailuoning injection on ischemia/reperfusion (I/R) injury in rats and its mechanism.</p><p><b>METHOD</b>Healthy male adult Sprague-Dawley (SD) rats were randomly divided into the sham operation group, the model group, the edaravone (3 mg x kg(-1)) control group, and Mailuoning high, middle and low-dose groups (4, 2, 1 mL x kg(-1)), with 10 rats in each group, and administered with drugs through tail intravenous injection. The middle cerebral artery occlusion (MCAO) was adopted to establish the rat ischemia/reperfusion model. After the ischemia for 2 h and reperfusion for 24 h, the pathological changes in neurovascular units (NVU) of brain tissues at the ischemia side was observed by HE staining. The expressions of glialfibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Ibal) were detected by the immunohistochemical method. The expressions of tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were detected by the western blotting technique.</p><p><b>RESULT</b>Mailuoning injection could significantly improve the pathological changes in cortical penumbra brain tissue UVN of (I/R) rats, reduce the number of GFAP and Ibal positive cells, and significantly decrease the expressions of TNF-alpha, IL-1beta, VCAM-1 and ICAM-1 of brain tissues of I/R rats.</p><p><b>CONCLUSION</b>Mailuoning injection shows an obvious protective effect on UVN of I/R rats. Its mechanism may involve the inhibition of the activation of astrocyte and microglia and the secretion and expression of various inflammatory factors.</p>


Subject(s)
Animals , Humans , Male , Rats , Brain , Metabolism , Brain Ischemia , General Surgery , Drugs, Chinese Herbal , Infarction, Middle Cerebral Artery , Genetics , Metabolism , Intercellular Adhesion Molecule-1 , Genetics , Metabolism , Protective Agents , Rats, Sprague-Dawley , Reperfusion Injury , Genetics , Metabolism , Tumor Necrosis Factor-alpha , Genetics , Metabolism , Vascular Cell Adhesion Molecule-1 , Genetics , Metabolism
19.
Acta Pharmaceutica Sinica ; (12): 1130-1135, 2014.
Article in Chinese | WPRIM | ID: wpr-299157

ABSTRACT

This study is to investigate the effect of the effective components group of Xiaoshuantongluo (XECG) on neuronal injury induced by oxygen-glucose deprivation (OGD) in primary cortical cultures isolated from SD rat cortex at day 3 and the possible mechanism. Cells were divided into control group, OGD model group and XECG group (1, 3 and 10 mg x L(-1)). The cell viability was assessed with MTT assay and the LDH release rate was measured by enzyme label kit. The cell apoptosis was analyzed using Hoechst staining. RT-PCR was applied to detect the mRNA levels of JAK2 and STAT3. Western blotting was used to detect the expressions of Bcl-2, Bax, p-JAK2 and p-STAT3 proteins. Results showed that XECG resulted in an obvious resistance to oxygen-glucose deprivation-induced cell apoptosis and decrement of cell viability, decrease the cell LDH release rate. XECG could adjust the expression of Bcl-2 and Bax proteins and increase Bcl-2/Bax ratio, up-regulate the expression of p-JAK2 and p-STAT3. In conclusion, XECG could protect against the neuronal injury cells exposed to OGD, which may be relevant to the promotion of JAK2/STAT3 signaling pathway, and impact the expression of Bax and Bcl-2.


Subject(s)
Animals , Rats , Apoptosis , Cell Survival , Cells, Cultured , Drugs, Chinese Herbal , Pharmacology , Glucose , Janus Kinase 2 , Metabolism , Neurons , Metabolism , Neuroprotective Agents , Pharmacology , Oxygen , Proto-Oncogene Proteins c-bcl-2 , Metabolism , STAT3 Transcription Factor , Metabolism , Signal Transduction , bcl-2-Associated X Protein , Metabolism
20.
Chinese Pharmaceutical Journal ; (24): 195-198, 2014.
Article in Chinese | WPRIM | ID: wpr-859850

ABSTRACT

OBJECTIVE: To investigate the salidroside on proliferation and apoptosis of human hepatocellular carcinoma HepG2 cells and its possible mechanisms of anti-tumor. METHODS: Cultured HepG2 cells in vitro were used as the research object and their cell morphology were observed by inverted microscope. The inhibitory rate of cell proliferation was measured by MTS assay. The cell apoptosis was determined by flow cytometry. The protein expressions of Bcl-2, Bax, caspase-3 and caspase-8 were detected by Western blot analysis. RESULTS: Salidroside could inhibit the proliferation of HepG2 cells and promote its apoptosis. The Bax, caspase-3 and caspase-8 protein expression were increased while Bcl-2 protein expression was decreased in HepG2 cells in a concentration-dependent manner. CONCLUSION: Salidroside can inhibit the proliferation and induce the apoptosis of HepG2 cells, and the mechanism may be associated with regulating protein expression of Bcl-2, Bax, caspase-3 and caspase-8.

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