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1.
Article in Chinese | WPRIM | ID: wpr-996514

ABSTRACT

ObjectiveTo explore the effects of modified Gualou Zhishitang combined with piperacillin sodium and tazobactam sodium on the immune function and serum levels of inflammatory cytokines in the patients with stroke-associated pneumonia (SAP, syndrome of phlegm-heat accumulation in lung). MethodEighty SAP patients with the syndrome of phlegm-heat accumulation in lung were randomized into a control group (40 cases) and a study group (40 cases). The SAP patients in the control group were treated with piperacillin sodium and tazobtam sodium, while those in the study group were treated with modified Gualou Zhishitang on the basis of the treatment in the control group for 2 consecutive weeks. The clinical therapeutic effects, immune function indexes, inflammation indexes, and lung function of SAP patients in the two groups before and after treatment were determined and compared. ResultAfter treatment, the scores of lesion, pulmonary rales, cough, fever, phlegm color, and constipation in both groups decreased (P<0.05). After treatment, the ratio of forced expiratory volume in the first second to forced expiratory volume (FEV1/FVC) and forced expiratory volume in the first second as percentage of predicted value(FEV1%) in both groups improved (P<0.05), and the study group outperformed the control group (P<0.05). The treatment decreased the neutrophil to lymphocyte ratio (NLR) in the two groups (P<0.05), and the study group had lower NLR than the control group after treatment (P<0.05). The serum levels of procalcitonin (PCT) and hypersensitive C-reactive protein (hs-CRP) in both groups declined after treatment (P<0.05), and the declines were more significant in the study group than in the control group (P<0.05). After treatment, the study group was better than the control group (P<0.05). The treatment in both groups elevated the levels of CD3+, CD4+, and CD4+/CD8+ in the peripheral blood and lowered the level of CD8+ (P<0.05), and the changes were more significant in the study group than in the control group (P<0.05). The total response rate of the study group was 95.00% (38/40), which was higher than that (80.00%, 32/40) of the control group (χ2=4.114,P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups. ConclusionModified Gualhou Zhishitang combined with piperacillin sodium and tazobactam sodium demonstrates a significant therapeutic effect on the SAP patients with the syndrome of phlegm-heat accumulation in lung. This therapy can mitigate the clinical symptoms, improve the lung function, lower the serum levels of inflammatory cytokines, and improve the immune capacity, with high safety.

2.
Journal of Clinical Hepatology ; (12): 2125-2129, 2022.
Article in Chinese | WPRIM | ID: wpr-942673

ABSTRACT

Exosomes (EXOs) are formed by intracellular multivesicular bodies and carry a variety of biomacromolecules such as lipids, proteins, encoding and non-coding RNAs, and mitochondrial DNA. EXOs can be released in vivo by different cell types, including hepatocytes, hepatic stellate cells, and immune cells and play the role of intercellular communication. More and more studies have shown that EXOs are involved in the development, progression, and prognosis of chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) infection and are expected to become potential biomarkers for the early diagnosis and prognostic evaluation of HBV-related HCC. This article reviews the role of EXOs in the host infection process of HBV and the importance of EXOs in the development, progression, and prognosis of CHB and HCC, in order to provide new ideas for the basic and clinical research in this field.

3.
Article in Chinese | WPRIM | ID: wpr-921970

ABSTRACT

OBJECTIVE@#To describe a family with intellectual developmental disorder with autism and speech delay (IDDAS) caused by a splice variant of TBR1 gene.@*METHODS@#A pregnant women with mental retardation, who also had a family history of mental retardation, was admitted to Prenatal Diagnosis Center of WanBei Coal and Electricity Group General Hospital Corporation in April 2019. Molecular genetic tests were performed on the pregnant women and ten other family members to analyze the pathogenic genotype. Functional assays of the pathogenic variant was carried out by minigene technology. With the determination of the genotype, prenatal diagnosis was carried out by amniotic fluid sampling.@*RESULTS@#Through whole exome sequencing, a novel splicing variant (c.1129-1G>C) was identified in the TBR1 gene of the proband, which has co-segregated with the disease phenotype in the family. The results of minigene assay showed abnormal splicing of exon 5. The variant was not detected in the fetal amniotic fluid. Fetal growth and development were normal one year after the birth.@*CONCLUSION@#The c.1129-1G>C variant of the TBR1 probably underlay the disease in of the pedigree. Timely prenatal genetic diagnosis and consultation can help to stop the transmission of the pathogenic variant.


Subject(s)
Female , Humans , Infant , Pregnancy , Autistic Disorder/genetics , China , Developmental Disabilities , Intellectual Disability/genetics , Language Development Disorders , Pedigree , T-Box Domain Proteins/genetics
5.
Acta Physiologica Sinica ; (6): 471-481, 2021.
Article in Chinese | WPRIM | ID: wpr-887682

ABSTRACT

Sleep exerts important functions in the regulation of cognition and emotion. Recent studies have found that sleep disorder is one of the important risk factors for Alzheimer's disease (AD), but the effects of chronic sleep deprivation on the cognitive functions of AD model mice and its possible mechanism are still unclear. In the present study, 8-month-old male APP/PS1/tau triple transgenic AD model (3xTg-AD) mice and wild type (WT) mice (n = 8 for each group) were subjected to chronic sleep deprivation by using the modified multiple platform method, with 20 h of sleep deprivation each day for 21 days. Then, open field test, elevated plus maze test, sugar water preference test, object recognition test, Y maze test and conditioned fear memory test were performed to evaluate anxiety- and depression-like behaviors, and multiple cognitive functions. In addition, the immunohistochemistry technique was used to observe pathological characteristics in the hippocampus of mice. The results showed that: (1) Chronic sleep deprivation did not affect anxiety- (P = 0.539) and depression-like behaviors (P = 0.874) in 3xTg-AD mice; (2) Chronic sleep deprivation exacerbated the impairments of object recognition memory (P < 0.001), working memory (P = 0.002) and the conditioned fear memory (P = 0.039) in 3xTg-AD mice; (3) Chronic sleep deprivation increased amyloid β (Aβ) deposition (P < 0.001) and microglial activation (P < 0.001) in the hippocampus of 3xTg-AD mice, without inducing abnormal tau phosphorylation and neurofibrillary tangles. These results indicate that chronic sleep deprivation exacerbates the impairments of recognition memory, working memory and conditioned fear memory in 3xTg-AD mice by aggravating Aβ deposition and the excessive activation of microglia in the hippocampus.


Subject(s)
Animals , Male , Mice , Alzheimer Disease , Amyloid beta-Peptides , Amyloid beta-Protein Precursor/genetics , Cognition , Disease Models, Animal , Mice, Inbred C57BL , Mice, Transgenic , Presenilin-1 , Sleep Deprivation , tau Proteins
6.
Chinese Journal of Urology ; (12): 26-31, 2020.
Article in Chinese | WPRIM | ID: wpr-869586

ABSTRACT

Objective To investigte the efficacy of docetaxel combined with androgen deprivation therapy for the treatment of metastatic hormone-sensitive prostate cancer based on Chinese population.Methods A total of 497 patients were enrolled from January 2004 to July 2018 in the Changhai Hospital.459 patients received androgen deprivation therapy alone and 38 patients received androgen deprivation therapy combined with docetaxel.The mean age was (72.1 ± 8.7)years.The median PSA level was 100.0 ng/ml,ranging 42.3-999.0 ng/ml.Patients of clinical T2,T3,T4 stage were 213 (42.9%),160 (32.2%),124(24.9%),respectively.Patients of clinical N0,N1,Nx stage were 319 (64.2%),144 (29.0%),34 (6.8%),respectively.Patients of clinical M0,M1a,M1b,M1c,Mx stage were 100(20.1%),51 (10.3%),332 (66.8%),9 (1.8%),5 (1.0%),respectively.Gleason scores of biopsy showed that 146 (29.4%) patients was ≤7,103(20.7%) was 8 and 248(49.9%)was ≥9.Propensity score matching was used to match the baseline between groups.Caliper value was set at 0.02.SPSS 22 software was used to achieve a 1:1 match between the two groups.There were no statistical difference in the age(P =0.102),PSA (P =0.713),T stage (P =0.113),N stage (P =0.226),M stage (P =0.514),Gleason score (P =0.612),tumor loading(P =0.812) between the two groups.The castration resistance-free rate and cancer specific survival rate of the two groups were compared by log-rank and breslow-wilcoxon test.Furthermore,forest plots were used to display the analysis results of different subgroups such as age,PSA,clinical stage,Gleason score,tumor load,whether patients had received palliative resection,and the differences in castration resistance-free rate were compared between the subgroups with high tumor load.Results The median follow-up time was 22.6 months in the androgen deprivation therapy group and 13.7 months in the combined therapy group.The number of patients with castration resistance in the two groups was 23 and 17,respectively.There were 3 and 6 deaths,respectively.There was no statistically significant difference in the overall progression time to castration resistance between the two groups (10.3 m vs.16.5 m,P > 0.05),and no statistically significant difference in the prostate cancer specific survival rate (21.9 m vs.14.8 m,P > 0.05).When subgroup analysis was performed,it was found that patients in the high-metastasis-volume subgroup who received the combination therapy had a significantly longer castration resistance free lifetime (10.6 m vs.7.2 m,P =0.044),but there was no significant difference in the low-metastasis-volume subgroup (10.5 m vs.12.6 m,P > 0.05).Conclusion Docetaxel combined with androgen deprivation therapy can improve the castration resistance free rate in patients with high metastasis volume,but not in low metastasis volume group.

7.
Article in Chinese | WPRIM | ID: wpr-863078

ABSTRACT

Tirofiban is a selective non-peptide glycoprotein Ⅱb/Ⅲa receptor inhibitor that reversibly inhibits fibrinogen-dependent platelet aggregation and subsequent thrombosis. Thrombosis caused by platelet activation plays a vital role in the occurrence and development of ischemic cerebrovascular events. Some studies have evaluated the use of tirofiban in intravenous thrombolysis and endovascular therapy. Although the optimal dose, conditions of use, and target patients have not been fully identified, the good tolerability of tirofiban and its efficacy in improving recanalization and long-term functional outcomes have been validated. This article reviews the mechanism of tirofiban and its application in the treatment of acute ischemic stroke reperfusion.

8.
Article in Chinese | WPRIM | ID: wpr-698672

ABSTRACT

BACKGROUND:During the percutaneous vertebroplasty, the optimal dose of bone cement that can bring favorable cement dispersion and remodel the biomechanical balance of the fractured vertebrae remains controversial. OBJECTIVE:To investigate the dispersion degree of small dose of bone cement in vertebroplasty. METHODS: In this experiment, 18 sheep selected with the same condition were randomly divided into three groups (group A, group B, group C), 6 in each group. A model of thoracolumbar vertebral compression fracture (T12, L1, L2) was made in each sheep. The injected volume of bone cement in groups A, B, C was 15%, 20%, 25% of the average volume of adjacent vertebral bodies, respectively. Postoperative CT images were used to evaluate the bone cement dispersion. Dispersion degree of bone cement among the three groups was compared by the Kruskal-Wallis test. RESULTS AND CONCLUSION:There was no statistical difference in the dispersion degree of bone cement among the three groups, and the excellent and good rate of dispersion was over 80%. To conclude, the optimal dose of bone cement injected into the fractured vertebra is 15% of the average volume of adjacent vertebral bodies, which can achieve good dispersion degree and restore the biomechanical stability of the vertebral body.

9.
Article in Chinese | WPRIM | ID: wpr-737200

ABSTRACT

This study was designed to evaluate the effects of drilling through the growth plate and using adipose-derived stem cells (ADSCs) and bone morphogenetic protein-2 (BMP-2) to treat femoral head epiphyseal ischemic necrosis,which can be done in juvenile rabbits.Passage-four bromodeoxyuridine (BrdU)-labeled ADSCs were cultured,assayed with MTT to determine their viability and stained with alizarin red dye to determine their osteogenic ability.Two-month-old,healthy male rabbits (1.2 to 1.4 kg,n=45) underwent ischemic induction and were randomly divided into five groups (group A:animal model control;group B:drilling;group C:drilling & ADSCs;group D:drilling & BMP-2;and group E:drilling & ADSCs & BMP-2).Magnetic resonance imaging (MRI),X-ray imaging,hematoxylin and eosin staining and BrdU immunofluorescence detection were applied 4,6 and 10 weeks after treatment.Approximately 90% of the ADSCs were labeled with BrdU and showed good viability and osteogenic ability.Similar results were observed in the rabbits in groups C and E at weeks 6 and 10.The animals of groups C and E demonstrated normal hip structure and improved femoral epiphyseal quotients and trabecular areas compared with those of the groups A and B (P<0.01).Group D demonstrated improved femoral epiphyseal quotients and trabecular areas compared with those of groups A and B (P<0.05).In summary,drilling through the growth plate combined with ADSC and BMP-2 treatments induced new bone formation and protected the femoral head epiphysis from collapsing in a juvenile rabbit model of femoral head epiphyseal ischemic necrosis.

10.
Article in Chinese | WPRIM | ID: wpr-735732

ABSTRACT

This study was designed to evaluate the effects of drilling through the growth plate and using adipose-derived stem cells (ADSCs) and bone morphogenetic protein-2 (BMP-2) to treat femoral head epiphyseal ischemic necrosis,which can be done in juvenile rabbits.Passage-four bromodeoxyuridine (BrdU)-labeled ADSCs were cultured,assayed with MTT to determine their viability and stained with alizarin red dye to determine their osteogenic ability.Two-month-old,healthy male rabbits (1.2 to 1.4 kg,n=45) underwent ischemic induction and were randomly divided into five groups (group A:animal model control;group B:drilling;group C:drilling & ADSCs;group D:drilling & BMP-2;and group E:drilling & ADSCs & BMP-2).Magnetic resonance imaging (MRI),X-ray imaging,hematoxylin and eosin staining and BrdU immunofluorescence detection were applied 4,6 and 10 weeks after treatment.Approximately 90% of the ADSCs were labeled with BrdU and showed good viability and osteogenic ability.Similar results were observed in the rabbits in groups C and E at weeks 6 and 10.The animals of groups C and E demonstrated normal hip structure and improved femoral epiphyseal quotients and trabecular areas compared with those of the groups A and B (P<0.01).Group D demonstrated improved femoral epiphyseal quotients and trabecular areas compared with those of groups A and B (P<0.05).In summary,drilling through the growth plate combined with ADSC and BMP-2 treatments induced new bone formation and protected the femoral head epiphysis from collapsing in a juvenile rabbit model of femoral head epiphyseal ischemic necrosis.

11.
Chinese Journal of Nephrology ; (12): 122-129, 2018.
Article in Chinese | WPRIM | ID: wpr-711095

ABSTRACT

Objective To investigate whether advanced glycation end products (AGEs) can induce the expression of Ros,JC-1 and its apoptosis-related proteins in glomerular mesangial cells under high glucose environment,induce apoptosis and injury of glomerular mesangial cells.Methods Rat glomerular mesangial cell line HBZY-1 was cultured in vitro.The cells were cultured with different concentrations of AGEs for 0,12,24 and 48 hours respectively.MTT assay was used to observe the cell proliferation ability.After the optimal time and concentration of AGEs were selected,the caspase enzyme inhibitor Z-VAD-fmk and reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC) were cultured and the apoptosis rate was detected by cell death detection apoptosis ELISA plus and Annexin V-FITC/PI kit.JC-1 staining was used to detect the changes of mitochondrial membrane potential (MMP).Cell ROX deep red flow cytometry was used to detect the total ROS level.The expression of anti-apoptotic protein Bcl-2,pro-apoptotic protein BAX,caspase-9,caspase-3 and poly ADP-ribose polymerase (PARP)-activated fragments was detected by Western blotting.Results AGEs could decrease the activity of glomerular mesangial cells in a time and concentration-dependent manner,and induce cell death.The percentage of apoptotic cells in glomerular mesangial cells was significantly increased after treatment with 250 mg/L AGEs for 24 h (P < 0.01),and Z-VAD-fmk could significantly alleviate AGEs-induced glomerular mesangial cell apoptosis (P < 0.01).Compared with the control group,AGEs increased the level of intracellular reactive oxygen species and decreased MMP in a time-dependent manner,and the two time points that AGEs significantly caused the change were 1 h and 2 h (all P < 0.01).AGEs also reduced the expression of antiapoptotic protein Bcl-2 and increased the expression of pro-apoptotic protein Bax,cleaved caspase-9,cleaved caspase-3 and cleaved PARP (all P < 0.01).Compared with AGEs group,NAC could significantly stabilize MMP (P < 0.01),increase Bcl-2 expression (P < 0.01),and decrease the expression of BAX,cleaved caspase-9,cleaved caspase-3 and cleaved PARP (all P < 0.01).Conclusion AGEs induce mitochondrial pathway apoptosis in glomerular mesangial cells by increasing intracellular ROS level and destroying MMP.

12.
Article in Chinese | WPRIM | ID: wpr-708823

ABSTRACT

Objective Using Cerenkov radiation energy transfer (CRET) effect of rare earth nanoparticles (RENPs) to enhance and convert Cerenkov luminescence into Cerenkov luminescence excited fluorescence,and to compare the accuracy of Cerenkov luminescence tomography (CLT) and Cerenkov luminescence excited fluorescence tomography (CLFT).Methods 68Ga (0.74 MBq) was used to respectively excite Y2O3 ∶Eu3+,Er2O3 and Eu2O3(10 mg/ml).Various radioactivities of 68Ga (3.70,1.85,0.92,0.46,0.23 MBq) were used to respectively excite Y2O3 ∶Eu3+ with a fixed concentration (10 mg/ml).A fixed radioactivity of 68Ga (3.70 MBq) was used to excite Y2O3 ∶Eu3+ with different concentrations (10.0,5.0,2.5,1.2,0.6 mg/ml) in order to find the relationships between the optical intensity and the radioactivity of 68Ga or the concentration of Y2O3 ∶Eu3+.Polyethylene tubes containing 68Ga (0.74 MBq) and 68Ga (0.74 MBq) +Y2O3 ∶Eu3+(1 mg) were respectively implanted into two nude mice,then PET/CT and optical imaging were acquired.Three-dimensional reconstruction was proceeded.One-way analysis of variance,two-sample t test,linear correlation analysis were used for data analysis.Results Y2O3 ∶Eu3+ could significantly and stably enhance the Cerenkov optical signal (F=53.35,q =17.03,P<0.001).The enhanced optical signal intensity had linear relationships with the radioactivity of 68Ga or the concentration of Y2O3 ∶Eu3+(r values:0.99and 0.93).Three-dimensional reconstruction result showed that CLFT had significantly higher similarity than CLT (0.43±0.14 vs 0.16±0.06,t =5.090,P<0.05).Conclusion CLFT could reflect the distribution of radiopharmaceuticals more precisely than CLT,and therefore might have potential in biologic optical imaging.

13.
Chinese Journal of Nephrology ; (12): 213-218, 2017.
Article in Chinese | WPRIM | ID: wpr-512122

ABSTRACT

Objective To investigate whether the effect of transient high glucose on inflammatory factors expression could be continuous in rat glomerular mesangial cell,and its relation with histone methylation modification.Methods Rat glomerular mesangial cells (HBZY-l) were divided into three groups:the high glucose group (25.0 mmol/L glucose),the hypertonic group (MA,5.5 mmol/L glucose+ 19.5 mmol/L mannitol) and the normal-glucose control group (5.5 mmol/L glucose),which were cultured for 24 h respectively.All 3 groups were then changed with normal-glucose medium to culture for 24 h,48 h and 72 h.Their protein,mRNA and supernatant were harvested.The protein expressions of mono-methylation of H3 lysine 4 (H3K4mel) was measured by Western blotting,and the mRNA expressions of NF-κB subunit p65 and set7/9 were determined by real timequantitative PCR.The expression of monocyte chemoattractant protein 1 (MCP-1) and vascular cell adhesion molecule 1 (VCAM-1) were detected by enzyme-linked immunosorbent assay.Results (1)Compared with those in normal control group,the expressions of H3K4mel protein and set7/9 mRNA were first up-regulated in high glucose group,then gradually down-regulated in the following 48 h normal-glucose medium (as compared with those at 0 h,all P < 0.05).At 72 h there was no statistic difference between high glucose group and normal control group (all P > 0.05).(2) Compared with those in normal control group,the up-regulated p65 mRNA,VCAM-1 and MCP-1 sustained at least for 72 h in high glucose group.Conclusions Transient high glucose can induce persistent inflammatory factors expression in rat glomerular mesangial cells,which may via histone modification.

14.
Chinese Journal of Nephrology ; (12): 48-54, 2017.
Article in Chinese | WPRIM | ID: wpr-506164

ABSTRACT

Objective To investigate the effects of abated microRNA-21 (miRNA-21) on phosphatase and tensin homologue on chromosome ten protein (PTEN) and PI3K/Akt/mTOR pathway,as well as their further influence on the autophagy in high glucose (HG,25.0 mmol/L) induced rat glomerular mesangial cells.Methods MiRNA-21 inhibitor and negative control were transfected by liposome 2000 into rat glomerular mesangial cells (HBZY-1).The cells were divided into normal glucose (5.5 mmol/L) group,normal glucose + negative control group,normal glucose +miRNA-21 inhibitor group,HG group,HG+negative control group and HG+miRNA-21 inhibitor group.Cell proliferation and hypertrophy were assayed by MTT and the ratio of total protein to cell number respectively.The miRNA-21 expression was detected using real time PCR.The expressions of PTEN/ Akt/mTOR signaling signatures,autophagy-associated protein (p62 and LC3 Ⅱ) and collagen Ⅰ was detected by Western blotting and real time PCR.Autophagosomes were observed using electron microscopy.Results Compared with those in normal glucose group,in HG group cells had hypertrophy and proliferation,up-regulated miRNA-21 expression,and down-regulated PTEN protein and mRNA expressions (all P < 0.01).Also there were and up-regulated p-Akt,p-mTOR,p62 and collagen Ⅰ expression,and lower LC3 Ⅱ expression and autophagosomes (all P < 0.01).Further,compared with those in HG group,cells hypertrophy and proliferation in HG+miRNA-21 inhibitor group were reduced,expressions of p-Akt,p-mTOR,p62 and collagen Ⅰ were down-regulated,while expressions of PTEN and LC3 Ⅱ and autophagosomes were up-regulated (all P < 0.01).Conclusions MiRNA-21 inhibitor up-regulates PTEN expression,which inhibits the activation of Akt/mTOR signaling pathway,ameliorates cell hypertrophy,proliferation and enhances autophagy to reduce extracellular matrix accumulation.

15.
Chinese Journal of Nephrology ; (12): 48-54, 2017.
Article in Chinese | WPRIM | ID: wpr-810890

ABSTRACT

Objective@#To investigate the effects of abated microRNA-21 (miRNA-21) on phosphatase and tensin homologue on chromosome ten protein (PTEN) and PI3K/Akt/mTOR pathway, as well as their further influence on the autophagy in high glucose (HG, 25.0 mmol/L) induced rat glomerular mesangial cells.@*Methods@#MiRNA-21 inhibitor and negative control were transfected by liposome 2000 into rat glomerular mesangial cells (HBZY-1). The cells were divided into normal glucose (5.5 mmol/L) group, normal glucose+negative control group, normal glucose+miRNA-21 inhibitor group, HG group, HG+negative control group and HG+miRNA-21 inhibitor group. Cell proliferation and hypertrophy were assayed by MTT and the ratio of total protein to cell number respectively. The miRNA-21 expression was detected using real time PCR. The expressions of PTEN/Akt/mTOR signaling signatures, autophagy-associated protein (p62 and LC3 Ⅱ) and collagen Ⅰ was detected by Western blotting and real time PCR. Autophagosomes were observed using electron microscopy.@*Results@#Compared with those in normal glucose group, in HG group cells had hypertrophy and proliferation, up-regulated miRNA-21 expression, and down-regulated PTEN protein and mRNA expressions (all P<0.01). Also there were and up-regulated p-Akt, p-mTOR, p62 and collagen Ⅰ expression, and lower LC3 Ⅱ expression and autophagosomes (all P<0.01). Further, compared with those in HG group, cells hypertrophy and proliferation in HG+miRNA-21 inhibitor group were reduced, expressions of p-Akt, p-mTOR, p62 and collagen Ⅰ were down-regulated, while expressions of PTEN and LC3 Ⅱ and autophagosomes were up-regulated (all P<0.01).@*Conclusions@#MiRNA-21 inhibitor up-regulates PTEN expression, which inhibits the activation of Akt/mTOR signaling pathway, ameliorates cell hypertrophy, proliferation and enhances autophagy to reduce extracellular matrix accumulation.

16.
Chinese Journal of Nephrology ; (12): 278-283, 2017.
Article in Chinese | WPRIM | ID: wpr-610009

ABSTRACT

Objective To observe the expression of microRNA-148b (miR-148b) induced by high glucose in rat mesangial cells,and to explore its effect on its target gene AMP-activated protein kinase α1 (AMPKα1) and extracellular matrix excretion.Methods Rat mesangial cells were divided ino 3 groups:normal glucose (NG,5.5 mmol/L glucose) group,hypertonic (MA,5.5 mmol/L glucose+19.5 mmol/L mannitol) group and high-glucose (HG,25.0 mmol/L glucose) group.MiR-148b expression was detected by real time PCR.Then miR-148b inhibitor was transfected to rat mesangial cells.Their protein expressions of AMPKα1,glucose regulated protein 78 (GRP78),C/EBP homologous protein (CHOP),fibronectin (FN) and collagen Ⅳ were detected by Western blotting.The expression of AMPKα1 mRNA was detected by real time PCR.The expression of collagen Ⅳ was also detected by immunofluorescence.Results Compared with NG group,HG group showed up-regulated miR-148bexpression,down-regulated AMPKαl mRNA and protein expressions,and up-regulated CHOP,GRP78,collagen Ⅳ and FN expressions (all P < 0.05).HG-induced mesangial cells with miR-148binhibitor had up-regulated AMPKα1 mRNA and protein expressions,and down-regulated CHOP,GRP78,collagen Ⅳ,FN expressions as compared with HG-induced cells without miR-148b inhibitor (all P < 0.05).Conclusions HG can up-regulate miR-148b expression and down-regulate AMPKα1 expression in rat mesangial cells,then activate endoplasmic reticulum stress to induce extracellular matrix excretion.MiR-148b inhibitor up-regulates AMPKα1 expression,inhibits endoplasmic reticulum stress and reduces extracellular matrix excretion.

17.
Chinese Journal of Nephrology ; (12): 447-452, 2017.
Article in Chinese | WPRIM | ID: wpr-617954

ABSTRACT

Objective To investigate the expression vibration of microRNA-503(miR-503) and its effect on target gene Bcl-2,caspase enzyme activity and apoptosis of human renal tubular epithelial cells (HK-2) induced by high glucose,and to clarify the pathogenesis of renal tubular injury induced by high glucose.Methods HK-2 cells were cultured in normal glucose group (NG),mannitol hypertonic control group (MA),and high glucose group (HG).The morphology of apoptotic cells was observed using inverted microscope.The expression of miR-503 was determined using realtime quantitative PCR.The apoptosis rate of HK-2 cells was detected by Annexin V-FITC double dye using flow cytometry instrument.The expression of Bcl-2 and cleaved caspase-9 were detected by Western blotting.Results In the high glucose and mannitol groups HK-2 cell,an obviously increased apoptotic rate was observed under inverted microscope compared with normal glucose group (P < 0.05).MA and HG up-regulated miR-503 expression (P < 0.01),down-regulated anti-apoptotic protein Bcl-2 expression (P < 0.05) and up-regulated cleaved caspase-9 (P < 0.05).Conclusions The expression of miR-503 increases in HK-2 cells cultured by high glucose and mannitol.MiR-503 promotes apoptosis of HK-2 cells via activating mitochondrial apoptotic pathways and enhancing cleaved caspase-9 for Bcl-2 insufficiency.The tubular toxicity of high glucose is partly due to osmotic pressure.The miR-503 may be involved in diabetic tubular injury and may be a new therapeutic target of DN.

18.
Article in Chinese | WPRIM | ID: wpr-256583

ABSTRACT

<p><b>OBJECTIVE</b>To observe the effect of RITA, a small molecule that targets p53, combined with temozolomide (TMZ) on proliferation, colony formation and apoptosis of human glioblastoma U87 cells and explore the underlying mechanism.</p><p><b>METHODS</b>Cultured U87 cells were treated with RITA (1, 5, 10, 20 µmol/L), TMZ, or RITA+TMZ (half dose) for 24, 48 or 72 h. MTS assay were used to detect the cell proliferation, and the cell proliferation rate and inhibitory rate were calculated. The effect of combined treatments was evaluated by the q value. The expressions of p53, p21 and other apoptosis-associated genes were detected by qRT-PCR and Western blotting; cell apoptosis was assayed using flow cytometry with Annexin V/PI double staining; colony formation of the cells was detected with crystal violet staining.</p><p><b>RESULTS</b>MTS assay showed that RITA at the 4 doses more potently inhibited U87 cell viability than TMZ at 72 h (P=0.000) with inhibitory rates of 25.94%-41.38% and 3.84%-8.20%, respectively. RITA combined with TMZ caused a more significant inhibition of U87 cells (29.21%-52.11%) than RITA (P<0.01) and TMZ (P=0.000) alone. At the doses above 5 µmol/L, the combined treatments with RITA+TMZ for 48 h resulted in q values exceeding 1.2 and showed an obvious synergistic effect of the drugs. Both RITA and TMZ, especially the latter, significantly increased the expressions of p53, p21, puma, and other apoptosis-associated genes to accelerate apoptosis and inhibit the growth and colony formation of U87 cells, and the effect was more obvious with a combined treatment.</p><p><b>CONCLUSION</b>RITA inhibits the growth of human glioblastoma cells and enhance their sensitivity to TMZ by up-regulating p53 expression, and when combined, RITA and TMZ show a synergistic effect to cause a stronger cell inhibition.</p>


Subject(s)
Humans , Apoptosis , Cell Line, Tumor , Cell Proliferation , Cell Survival , Dacarbazine , Pharmacology , Furans , Pharmacology , Glioblastoma , Drug Therapy
19.
Chinese Pharmacological Bulletin ; (12): 131-135, 2015.
Article in Chinese | WPRIM | ID: wpr-462504

ABSTRACT

Aim To determine the plasma protein binding rate of five components of Eucommia ulmoides extract. Methods The equilibrium dialysis method was used to study the plasma protein binding rate. The plasma samples were extracted by protein precipitation with methanol. With the use of puerarin as the internal standard, UPLC-MS/MS was carried out to determine the concentration of the five compounds in and out of the dialysis membrane. Results The average plasma protein binding rates of five compounds on the area of the concentration which was determinate were as fol-lows, respectively: geniposidic acid was ( 25. 77 ± 2. 68 )%, protocatechuic acid was ( 57. 54 ± 3. 79)%, chlorogenic acid was (53. 91 ± 3. 00)%, pinoresinol diglucoside was (24. 15 ± 4. 92)%, and pinoresinol singleglucoside was (49. 78 ± 3. 61)%. Conclusions The results show that the binding percentage of geniposidic acid and pinoresinol diglucoside is relatively low, but the binding rate of the others with rat plasma protein is moderate.

20.
The Journal of Practical Medicine ; (24): 2969-2971, 2015.
Article in Chinese | WPRIM | ID: wpr-481117

ABSTRACT

Objective To investigate the association between the glycated albumin to glycated hemoglobin (GA/A1c) ratio and carotid plaque. Methods Type 2 diabetic (T2DM) patients in endocrine inpatient department of Sichuan Provincial People′s Hospital were chosen whose clinical data were collected. Results Of the recruited 154 T2DM patients , GA/HbA1c ratio was negatively correlated with BMI , blood uric acid and was positively correlated with age, HCY, FBG, PBG, left carotid IMT and right carotid IMT. In terms of carotid plaque, GA, GA/HbA1c ratio and HCY were higher in carotid plaque positive patients than those without carotid plaque. The results of logistic regression analysis showed that GA/HbA1c ratio was significantly associated with the presence of carotid plaque (P=0.008). Conclusions GA/HbA1c ratio was positively correlated with the presence of carotid artery IMT in T2DM This suggests that GA/HbA1c ratio will serve as a useful clinical marker for predicting diabetic cardiovascular complications.

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