1.Effect of propofol on apoptosis of cortical astrocytes isolated from neonatal rats
Shuncui LIU ; Zhenyi CHEN ; Xiaoting HUANG ; Ruizhe LIAO
Chinese Pharmacological Bulletin 2017;33(5):691-695
Aim To study the effects of propofol on apoptosis of cortical astrocytes isolated from neonatal rats.Methods Pure astrocytes(AST)were obtained from the cultured cerebral cortical cells and identified by the GFAP stain technology in neonatal rats.AST cells were treated with different concentrations of propofol(0,10,30,90 μmol·L-1)for 8 hours.Cell viability was measured by MTT method,and the apoptosis was detected by Annexin V/PI double staining.Cytochrome C(cyt-C)leakage was detected by Western blot.Caspase-3 and caspase-9 activities were measured by spectrophotometry.Results AST cells were administered with different concentrations of propofol(0,10,30,90 μmol·L-1)for 8 hours.It decreased the survival rate in a concentration-dependent manner,induced the leakage of cyt-C in mitochondria,up-regulated the expression of pro-apoptotic protein caspase-3 and caspase-9,and induced AST apoptosis.Conclusion Propofol induces the apoptosis of astrocytes in neonatal rat cortex in vitro,which may be related to the activation of mitochondria apoptosis pathway induced by mitochondrial cyt-C release.
2.Interferon-induced protein 44 is correlated with clinical features of patients with systemic lupus erythematosus
Lianjie SHI ; Xiangyang HUANG ; Min LI ; Yang YE ; Zhenyi ZHAO ; Xue ZHONG ; Nanping YANG
Chinese Journal of Rheumatology 2011;15(1):26-29
Objective To investigate the expression of interferon-induced protein 44 (IFI44) gene in the leukocytes of the peripheral blood samples from patients with systemic lupus erythematosus (SLE), and to evaluate the relationship between the expression level and disease activity. Methods Mononuclear cells in the peripheral blood samples from 100 SLE patients were compared with those of 40 disease controls and 40 healthy donors (HD) and the expression of the IFI44 was evaluated by quantitative real-time PCR.Comparisons between groups were performed with ANOVA, and the correlation analysis between the level of expression was higher in SLE patients than disease controls and healthy donors (26.8±5.3, 7.4±2.7, 5.2±2.0,respectively) (P=0.0012, P=0.005), but no difference was found between disease controls and healthy donors. Mild disease activity and the SLE patients with stable disease (63.1±22.4, 28.0±7.2, 9.2±1.8, respectively)and 24 hours urine protein level (r=0.42, P=0.000). Conclusion IFI44 is demonstrated to be highly expressed in SLE patients. The level of IFI44 may be a promising candidate biomarker for identifying SLE activity.
3.Modeling of p53 signaling pathway based on S-system equations.
Shunhui LIU ; Changli TAO ; Zhenyi HUANG ; Shulin HUANG
Journal of Biomedical Engineering 2010;27(3):505-510
p53, as a transcription factor, is an important tumor suppressor gene and plays the key role in the p53-dependent gene regulatory network. Therefore, it is important to understand its biological function at the level of the whole system. In this paper, based on KEGG database and related literatures in English and Chinese, the interaction mode and quantitative relationship of the related molecules involved in p53 signaling pathway were extracted. By using S-system equations and 'Simulink' toolbox of Matlab7.0, a dynamic model of p53 signaling pathway was developed, and the dynamic regulatory characteristics of p53 signaling pathway were analyzed on model simulation. The results were in accord with the literatures and could reflect quantitatively the complex regulatory relationship between the interacting molecules involved in p53 signaling pathway. In addition, model simulation helped us find and identify the key molecules in this signaling pathway. Thus, this model can be used as a basis for the follow-up study of the relationship by precise and quantitative assessment.
Algorithms
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Computer Simulation
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Gene Expression Regulation
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Humans
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Models, Biological
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Signal Transduction
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physiology
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Transcription Factors
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genetics
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metabolism
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Tumor Suppressor Protein p53
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genetics
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physiology
4. Effects of remifentanil combined with propofol on hemodynamics and inflammatory stress in patients with septic shock
Linyang YE ; Yangyang NIE ; Qingxiang WANG ; Xi HUANG ; Weijie CHEN ; Zhenyi CHEN
Chinese Journal of Primary Medicine and Pharmacy 2019;26(11):1325-1330
Objective:
To investigate the effects of remifentanil combined with propofol on hemodynamics, inflammatory stress response and immune function in patients with acute abdomen complicated with septic shock.
Methods:
From June 2017 to August 2018, 112 patients with acute abdomen complicated with septic shock who admitted to the First Affiliated Hospital of Xiamen University were enrolled in the study.They were randomly divided into observation group and control group according to the digital table, with 56 cases in each group.The control group was anesthetized with sevoflurane combined with propofol.The observation group was anesthetized with remifentanil combined with propofol.The hemodynamic parameters of the patients entering the operating room(T0), 0.5h(T1), 1h(T2) and awake(T3) after anesthesia were recorded.The intraoperative norepinephrine dosage was recorded.The inflammatory response, stress response and immune function indicators at T0, T2 and T3 were recorded.
Results:
Compared with T0, T1 and T2, the MAP of the two groups was higher at T3, and the differences were statistically significant(
5.Comprehensive analysis of the functional role of lncRNA GAS5 in triple-negative breast cancer by bioinformatics
Zhenyi HUANG ; Jia SONG ; Zinan LU ; Gang SUN
Chinese Journal of Endocrine Surgery 2020;14(2):119-123
Objective:To study the effect of long noncoding RNA growth arrest-specifific transcript 5 (lncRNA GAS5) on the occurrence and development of triple-negative breast cancer (TNBC) by analyzing the differential expression of lncrna GAS5 in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases.Methods:The expression of GAS5 in each subtype and pathological stage of breast cancer was studied by the TCGA data. The correlation of GAS5 was analyzed by using TNBC data GSE76124 and GSE83937 from the GEO database of the United States. The elated genes were collected and take the intersection. The positive correlation genes were used to analyze the GO function and the enrichment of KEGG pathway. GSEA of GAS5 was analyzed with TCGA database and GEO76124 data. GSE40525 and GSE76250 were selected from GEO data set to screen different miRNA and mRNA of TNBC, and construct the ceRNA network of GAS5-mirna-mrna through prediction.Results:The expression of GAS5 in breast cancer was lower than that in the adjacent tissues. GAS5 was mainly involved in various metabolic processes, including organic metabolism, macromolecular metabolism, nitrogen metabolism, etc. In terms of pathway, GAS5 mainly affected the ribosome biogenesis in eukaryotes, Wnt signaling pathway. By constructing the regulatory network of GAS5 in TNBC, we found that GAS5 was most likely to regulate the expression of 25 genes including SLC7A2 and lLONRF2 by adsorbing hsa-mir-650 and has-mir-532-5p.Conclusion:lncrna GAS5 may play a role of tumor suppressor gene in breast cancer and provide a new therapeutic target for gene therapy of breast cancer.
6.Pharmacokinetics of intravenous arsenic trioxide in the treatment of acute promyelocytic leukemia
Jianhua NI ; Guoqiang CHEN ; Zhixiang SHEN ; Xiushong LI ; Haiwei LIU ; Yanting HUANG ; Zhiwen FANG ; Saijuan CHEN ; Zhenyi WANG ; Zhu CHEN
Chinese Medical Journal 1998;(12):1107-1110
Objective To study the pharmacokinetics and metabolism of arsenic trioixide (As2O3) and its main side effects.Method As2O3 was administered intravenously at the dose of 10 mg per day for the treatment of 8 relapsed acute promyelocytic leukemia (APL) patients. The arsenic content was measured by Gas-phase chromotography. Results The plasma maximal concentration (Cpmax) was 0.94±0.37 mg/L (±s), time to peak concentration (Tp) was 4 hours, plasma distribution half-time (t1/2α) and elimination half-time (t1/2β) were 0.89±0.29 hours and 12.13±3.31 hours, respectively. Apparent distribution volume (Vc) was 3.83±0.45 L, system clearance (CLs) was 1.43±0.17 L/h, and area under curve (AUC) was 7.25±0.97 mg*h/L. The continuous administration of As2O3 did not alter its pharmacokinetic behaviors. During As2O3 treatment, 24-hour arsenic content in urine accounted for 1%-8% of the dialy dose (10 mg). When arsenic accumulation in hair and nail increased continuously, the peak concentration could be five to seven-fold higher than that of pre-treatment. Importantly, arsenic contents in both urine and hair or nail declined gradually after drug withdrawal. No bone marrow suppression or severe organ-impairment was found.Conclusion As2O3 is a relatively safe and effective remedy in the treatment of patients with relapsed APL, in spite of certain degree of arsenic accumulation in some tissues.
7.Randomized controlled trial on application of negative pressure materials of polyvinyl alcohol and polyurethane in full-thickness burn wounds after escharotomy
Zhen HUANG ; Peng WANG ; Zhenyi PAN ; Liang DONG ; Jian SU ; Nengwu XU
Chinese Journal of Burns 2020;36(9):813-820
Objective:To compare the effects and characteristic difference of negative pressure materials of polyvinyl alcohol and polyurethane in the treatment of full-thickness burn wounds after escharotomy.Methods:From January 2018 to December 2019, 60 patients with full-thickness burns who met the inclusion criteria and hospitalized in Xuzhou Renci Hospital were recruited in this prospective randomized controlled trial. According to the random number table, 60 cases were divided into polyvinyl alcohol group ( n =30, 13 males and 17 females) and polyurethane group ( n =30, 14 males and 16 females), aged (34±7) and (35±6) years respectively, with burn area of 4.20% (2.23%, 4.90%) total body surface area (TBSA) and 3.89% (2.18%, 4.76%)TBSA and escharectomy area of 2.70% (1.97%, 3.42%) TBSA and 2.87% (2.12%, 3.34%)TBSA, respectively. After patient′s admission, debridement was immediately performed on the full-thickness burn wound, and the dressing was changed with iodophor once a day. Escharectomy was performed on post injury day 3. After thorough hemostasis and washing the wounds with normal saline, patients of the two groups chose corresponding foam materials and supporting facilities for continuous negative-pressure treatment for 1 week, with the negative pressure value setting at -19.9 kPa. Installation time of negative-pressure material was recorded. After a week of negative-pressure treatment, the maximum pulling force of removing foam material was recorded to evaluate the adhesional degree between foam materials and wounds. The amount of bleeding in the process of removing foam materials was recorded, hyperplasiaof granulation tissue was observed with hematoxylin eosin (HE) staining, and the expression of CD31 was detected by immunohistochemical staining and Western blotting to denote vascularization. The ratio of R1 to R0 of coefficient of restitution of foam material before and one week after negative-pressure treatment and drainage volume of wound exudate within a week of negative-pressure treatment were recorded to denote the drainage ability of foam material to wound exudate. One week after negative-pressure treatment, the bacterial colonization, residual foreign body, and eczema rate of skin edge were recorded. Data were statistically analyzed with chi-square test, independent-sample t test, and Mann-Whitney U test. Results:(1) Installation time of negative-pressure material of patients in polyurethane group was (14±3) min, which was significantly shorter than (18±3) min in polyvinyl alcohol group ( t=2.788, P<0.01). (2) One week after negative-pressure treatment, the maximum pulling force of removing foam material of patients in polyvinyl alcohol group was (6.4±0.4) N, which was significantly lower than (16.7±0.8) N in polyurethane group ( t=12.010, P<0.01). (3) One week after negative-pressure treatment, the volume of wound bleeding of patients in polyvinyl alcohol group was (20±3) mL in the process of removing foam material, which was significantly less than (59±3) mL in polyurethane group ( t=50.200, P<0.01). (4) One week after negative-pressure treatment, HE staining showed that hyperplastic thickness of wound granulation tissue of patients in polyurethane group was (2.3±0.6) mm which was significantly higher than (1.6±0.4) mm in polyvinyl alcohol group ( t=6.667, P<0.01); immunohistochemical staining showed that the number of microvascular lumen in wound granulation tissue of patients in polyurethane group was significantly more than that in polyvinyl alcohol group; Western blotting showed that protein expression of CD31 in wound granulation tissue of patients in polyurethane group (1.00±0.05) was significantly higher than 0.42±0.03 of polyvinyl alcohol group ( t=10.490, P<0.01). (5)The ratio of R1 to R0 of coefficient of restitution of foam material of patients in polyvinyl alcohol group was 0.39±0.19, which was significantly lower than 0.52±0.16 in polyurethane group ( t=2.975, P<0.01). In patients of polyvinyl alcohol group, the drainage volume of wound exudate of foam material during one week after negative-pressure treatment was (1 258±444) mL, significantly less than (1 658±580) mL of polyurethane group ( t=3.003, P<0.01). (6) One week after negative-pressure treatment, the number of residual foreign body in wounds of patients of polyurethane group was (14.14±0.37) particles, which was significantly more than (3.36±0.15) particles in polyvinyl alcohol group ( t=26.200, P<0.01). The level of bacterial colonization of wounds and eczema rate of skin edge of patients between the two groups were close. Conclusions:Polyurethane foam material is easy to install and operate, relatively difficult to dry and shrink, and has strong ability to discharge wound exudation. Polyurethane foam material is better than polyvinyl alcohol foam material in promoting wound angiogenesis and tissue proliferation. Polyurethane foam material can be chosen firstly for the wounds with need of protecting deep tissues and important organs, as well as the wounds with obvious inflammatory edema and serious contamination. Polyvinyl alcohol foam material is less adherent to wounds, which is better than polyurethane foam material in the aspects of reducing wound bleeding and residual foreign body. Polyvinyl alcohol foam material can be firstly selected to fix and promote skin graft survival after skin grafting, wound bed preparation before skin grafting of burn with large area and deep wound cavity or sinus, etc. Both types of foam materials need to be improved in the aspects of bacterial colonization and prevention and treatment of skin eczema.
8.Discussion on mechanism and experimental validation of Bupiwei Xieyinhuo Shengyang Prescription in treatment of gastroesophageal reflux disease based on network pharmacology
Yalin LIANG ; Meizhen HUANG ; Yunyan ZHANG ; Maoguang HUANG ; Liqun LI ; Zhenyi LUO ; Huaying MENG ; Sheng XIE
International Journal of Traditional Chinese Medicine 2023;45(3):315-322
Objective:To explore the possible mechanism of Bupiwei Xieyinhuo Shengyang Prescription on gastroesophageal reflux disease (GERD) based on network pharmacology and molecular docking technology.Methods:The main active components and target information of Bupiwei Xieyinhuo Shengyang Prescription were screened by TCMSP database, and targets were identified by GeneCards, OMIM, TTD and PharmGKB databases. The intersection of active ingredient components and disease targets was selected to construct PPI network by STRING. Cytoscape CytoNCA plug-in was used to extract core targets for analysis. GO function enrichment and KEGG pathway enrichment analysis were performed using Metascape. Cytoscape 3.7.2 was used to construct the "component-target-signal pathway" network, and Autodock was used to complete molecular docking verification. Animal experiments were further used for verification. SPF SD male rats were selected and GERD model was established by esophageal stent implantation. After 14 days of intervention, serum TNF-α and COX-2 levels of rats in each group were detected for verification.Results:A total of 215 effective compounds were screened from Bupiwei Xieyinhuo Shengyang Prescription. The main targets of GERD were TNF, IL6, CASP3, TP53 and PTGS2, which mainly focused on cancer pathway, AGE-RAGE signaling pathway, calcium signaling pathway and NF-κB signaling pathway. The results of molecular docking showed that the binding potential and activity of the key active components of Bupiwei Xieyinhuo Shengyang Prescription and the core target were better. Compared with the model group, Bupiwei Xieyinhuo Shengyang Prescription could reduce the serum expression levels of TNF-α and COX-2 ( P<0.01). Conclusions:By regulating TNF, IL6, CASP3, TP53, PTGS2 and other core targets, Bupiwei Xieyinhuo Shengyang Prescription can regulate NF-κB signaling pathway, calcium signaling pathway and other signaling pathways to play a role in the treatment of GERD.
9.Gait abnormalities among elderly persons with type 2 diabetes and peripheral neuropathy
Jiayu ZHU ; Haiyan YU ; Zhenyi WAN ; Yangfan SUN ; Shuai YAO ; Zhida JIANG ; Lan CHEN ; Yu CHEN ; Guilan HUANG ; Rongzheng YUAN
Chinese Journal of Physical Medicine and Rehabilitation 2022;44(12):1090-1094
Objective:To explore the features the gait of elderly persons with type 2 diabetes and peri-pheral neuropathy.Methods:Twenty patients no less than 60 years old with type 2 diabetes and peripheral neuropathy (DPN) formed a DPN group, while 20 counterparts with type 2 diabetes but without peripheral neuropathy composed the DM group, and another 20 healthy counterparts served as a control group. The three groups were tested using the Swedish Qualisys motion capture system and their walking speed, step length, step width, stride frequency and stride length, bipedal foot support phase time, single foot support phase time, peak plantar pressure, and regional-holding time were collected and compared.Results:The average walking speed, stride length and stepping frequency of the DPN group were all significantly lower than the other 2 groups′ averages. Their bipedal support phase was significantly longer, but their single foot support phase time was significantly shorter. And in the DPN group the average first and second peak plantar pressures and the second peak pressure time were significantly greater than the other groups′ averages.Conclusions:Elderly patients with type 2 diabetes and peripheral neuropathy have significant gait abnormalities, decreased walking stability, as well as increased plantar pressure and plantar compression time.
10.Arsenic trioxide induces multiple myeloma cell apoptosis viadisruption of mitochondrial transmembrane potentials and activation of caspase-3
Peimin JIA ; Guoqiang CHEN ; Xiaojun HUANG ; Xun CAI ; Jie YANG ; Long WANG ; Yuhong ZHOU ; Yulei SHEN ; Li ZHOU ; Yun YU ; Saijuan CHEN ; Xueguang ZHANG ; Zhenyi WANG
Chinese Medical Journal 2001;114(1):19-24
Objective To investigate the response of multiple myeloma (MM) cells to arsenic trioxide (As2O3) and their possible mechanisms. Methods Two MM-derived cell lines RPMI8226 and U266 cells were used as in vitro models. Cell apoptosis was assessed by morphology, flow cytometry, and DNA gel electrophoresis. Mitochondrial transmembrane potentials (△Ψm) were evaluated by measuring cellular Rhodamine 123 staining intensity. Protein expression was analyzed using Western blot. Results Zero point one to 0.5?μmol/L As2O3 inhibited cell proliferation and 2.0?μmol/L As2O3 induced cell apoptosis, while 1.0?μmol/L As2O3 inhibited proliferation with a weak degree of apoptosis induction in RPMI8226 and U266 cell lines. As2O3-induced apoptosis was accompanied by mitochondrial transmembrane potentials (△Ψm) collapse and caspase-3 activation in the presence of intact membrane. Glutathione depleter buthionine sulfoximine enhanced, while disulfide bond-reducing agent dithiothreitol partially antagonized As2O3-induced △Ψm collapse and apoptosis in MM cells. All-trans retinoic acid (ATRA) could also induce apoptosis in RPMI8226 cells, but it did not show any cooperative effects with As2O3. Conclusion As2O3 exerts apoptosis-inducing and growth-inhibiting effects on MM cells, and mitochondrium is a pivotal and common target of As2O3 for apoptosis induction.