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1.
Chinese Pharmacological Bulletin ; (12): 1740-1745, 2023.
Artículo en Chino | WPRIM | ID: wpr-1013952

RESUMEN

Aim To explore the important role of HDAC5 in P-gp expression in rats in high-altitude low oxygen environment and its effect on phenytoin sodium pharmacokinetics. Methods Wistar rats were transported to Batang, Yushu, Qinghai, at an altitude of 4010 m, with 6 rats in each group, divided into 1 d and 3 d groups. Different groups were given phenytoin, phenytoin combined with hypericin, and phenytoin combined with verapamil. Plasma and liver tissues were collected at different time after taking the drug in the plateau area. The concentration of phenytoin sodium in plasma was determined by UFLC-MS method. Changes in protein expression were detected by Western blot. Results The results of UFLC-MS showed that the AUC

2.
Chinese Pharmacological Bulletin ; (12): 65-70, 2023.
Artículo en Chino | WPRIM | ID: wpr-1013879

RESUMEN

Aim To explore the effect of salidroside on the learning and memory ability of mice under high altitude hypoxia. Methods Forty-eight C57BL/6J male mice were randomly divided into plain control group, plateau model group and salidroside group according to their body weight, with 16 mice in each group. The animals in each group were given prophylactic doses for three days and then rushed to a plateau with an altitude of 4 010 m. After one day of hypoxia exposure, Morris water maze was performed to test the learning and memory ability of mice; malondialdehyde(MDA), hydrogen peroxide(H

3.
Acta Physiologica Sinica ; (6): 691-702, 2023.
Artículo en Chino | WPRIM | ID: wpr-1007784

RESUMEN

The plateau environment is characterized by low oxygen, low air pressure, low temperature, and strong ultraviolet rays, etc. Chronic obstructive pulmonary disease (COPD) is a preventable and treatable chronic lung disease. High altitude environment increases COPD prevalence, clinical manifestation and mortality. The therapeutic window of theophylline drugs for COPD is narrow, and the high altitude environment has an influence on the pharmacokinetics of the drugs. This review summarizes the differences in the prevalence, mortality, clinical manifestation and clinical symptoms of COPD in the plateau and plain, providing a basis for identifying the risk factors of COPD in the plateau areas. The effects of plateau hypoxic environment on the pharmacokinetics of COPD drugs were also discussed. It can provide a rationale for more effective prevention and treatment of COPD at high altitude.


Asunto(s)
Humanos , Altitud , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Oxígeno , Hipoxia
4.
Journal of Forensic Medicine ; (6): 262-270, 2023.
Artículo en Inglés | WPRIM | ID: wpr-981859

RESUMEN

OBJECTIVES@#To compare the application value of the likelihood ratio (LR) method and identity by state (IBS) method in the identification involving half sibling relationships, and to provide a reference for the setting of relevant standards for identification of half sibling relationship.@*METHODS@#(1) Based on the same genetic marker combinations, the reliability of computer simulation method was verified by comparing the distributions of cumulated identity by state score (CIBS) and combined full sibling index in actual cases with the distributions in simulated cases. (2) In different numbers of three genetic marker combinations, the simulation of full sibling, half sibling and unrelated individual pairs, each 1 million pairs, was obtained; the CIBS, as well as the corresponding types of cumulative LR parameters, were calculated. (3) The application value of LR method was compared with that of IBS method, by comparing the best system efficiency provided by LR method and IBS method when genetic markers in different amounts and of different types and accuracy were applied to distinguish the above three relational individual pairs. (4) According to the existing simulation data, the minimum number of genetic markers required to distinguish half siblings from the other two relationships using different types of genetic markers was estimated by curve fitting.@*RESULTS@#(1) After the rank sum test, under the premise that the real relationship and the genetic marker combination tested were the same, there was no significant difference between the simulation method and the results obtained in the actual case. (2) In most cases, under the same conditions, the system effectiveness obtained by LR method was greater than that by IBS method. (3) According to the existing data, the number of genetic markers required for full-half siblings and half sibling identification could be obtained by curve fitting when the system effectiveness reached 0.95 or 0.99.@*CONCLUSIONS@#When distinguishing half sibling from full sibling pairs or unrelated pairs, it is recommended to give preference to the LR method, and estimate the required number of markers according to the identification types and the population data, to ensure the identification effect.


Asunto(s)
Humanos , Hermanos , Marcadores Genéticos , Simulación por Computador , Síndrome del Colon Irritable/genética , Reproducibilidad de los Resultados , Genotipo
5.
Journal of Forensic Medicine ; (6): 459-467, 2022.
Artículo en Inglés | WPRIM | ID: wpr-984136

RESUMEN

OBJECTIVES@#To explore the damage effects of chronic restraint stress (CRS) on amygdala cells through the rat CRS model.@*METHODS@#The rat CRS model was established, and the changes in body weight and adrenal mass in control group and CRS group were monitored at 1 d, 7 d, 14 d and 21 d. The behavior changes were evaluated by the percentage of retention time of open arms and open arm entries using the elevated plus maze (EPM). ELISA was used to detect the concentrations of rat's corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol. The changes of expression of glucocorticoid receptor (GR) and glial fibrillary acidic protein (GFAP) in amygdala were determined by immunohistochemistry and Western blotting. Ultrastructure changes of glial cell were observed by transmission electron microscopy. The apoptosis rate of amygdala was measured by flow cytometry.@*RESULTS@#Compared with the control group at the same time points, body weight of CRS 1 d, 7 d, 14 d and 21 d groups increased slowly, but adrenal mass increased significantly; the serum level of CRH, cortisol and ACTH increased significantly at 7 d, 14 d and 21 d respectively; the expression of GR in amygdala was increased while that of GFAP was decreased; EPM test suggested that the percentage of retention time of open arms and open arm entries decreased significantly after 14 d. The CRS group showed different degrees of glial cell damage in amygdala, and the apoptosis rate of glial cell was significantly increased in 21 d group.@*CONCLUSIONS@#This study successfully established a CRS model in rats, and anxiety-like behavioral changes in model rats may be caused by apoptosis of amygdala astrocytes.


Asunto(s)
Ratas , Animales , Hidrocortisona/farmacología , Amígdala del Cerebelo/metabolismo , Hormona Adrenocorticotrópica/farmacología , Apoptosis , Peso Corporal
6.
Journal of International Pharmaceutical Research ; (6): 283-289, 2020.
Artículo en Chino | WPRIM | ID: wpr-845188

RESUMEN

Objective: To prepare graphene oxide(GO)/polycaprolactone(PCL)composite matrix nanomaterials with different concentrations, and investigate effects of the nanomaterials on the myocardial differentiation of rat brown adipose stem cells (BASC)in vitro. Methods: The GO/PCL composite nanofiber materials were prepared by electrospinning technology. The biocompatibility of the nanomaterials was tested by the CCK-8 assay after cultivation of the BASC on the pure PCL and GO/PCL composite nanofibers, and the characterization of the nanofiber materials was performed by the scanning electron microscopy(SEM)and electrical conductivity measurement. The expression of cardiomyocyte-related proteins was examined by the cytological method and immunofluorescence staining. The GO/PCL composite nanofiber materials were systematically evaluated for their effect on the viability, proliferation and myocardial differentiation of BASC. Results: The GO/PCL composite nanofiber materials showed no obvious cytotoxicity at the 0.1 mg/ml GO concentration. The statistical results for the protein fluorescence intensities showed that the expression of the cardiomyocyte specific protein, α-actinin, and the intercalated disc-related protein, connexin-43(CX-43), was significantly increased in the GO/PCL group than in the PCL group(P<0.05). The cytoskeletal staining results showed that, compared with the PCL group, the cells in the GO/PCL group showed a long spindle-like stretch similar to the natural myocardial cell bundle, and the growth direction had a certain polarity. Conclusion: This study successfully prepared GO/PCL composite nanomaterials, which could promote the differentiation of BASCs into cardiomyocytes and the expression of intercalated disc-related proteins.

7.
Chinese Journal of School Health ; (12): 854-857, 2019.
Artículo en Chino | WPRIM | ID: wpr-818669

RESUMEN

Objective@#To investigate the relationships between behavioral problems and family environment in obese children aged 6-15 years to provide a dereference for the analysis of behavioral problems among obese children and the construction of their family environmet .@*Methods@#Family environment dimensions and behavioral problems were investigated among 2 376 obese children and 2 376 non-obese children with Family Environment Scale Symptoms Questionnaire and Achenbach Child Behavior Checklist. Data were analyzed by SPSS 17.0.@*Results@#The incidence of the behavioral problems in obese children (21.12%) was higher than that of non-obese children (15.53%)(χ2=24.93,P<0.01).The scores of Family Environment Scale Symptoms Questionnaire differed between obese children and nonobese children (Z=-2.44, -2.98, -3.38, P<0.05). Binary logistic regression results showed that for obese boys and girls aged 6 to 11 years, high maternal education levels(OR=0.78, 95%CI=0.69-0.88), family cohesion(OR=0.75, 95%CI=0.67-0.84) and less family conflicts(OR=0.81, 95%CI=0.75-0.87) were related to less behavioral problems; for obese boys and girls aged 12 to 15 years, family cohesion(OR=0.79, 95%CI=0.70-0.90) and less family conflicts(OR=0.78, 95%CI=0.71-0.86) were related to less behavioral problems.@*Conclusion@#Family cohesion and less family conflicts might help low the risk of behavioral problems among obese children. The role of family environment on behavioral problems should not be neglected in future mental health promotion and social work service for obese children.

8.
Chinese Journal of Practical Gynecology and Obstetrics ; (12): 985-989, 2019.
Artículo en Chino | WPRIM | ID: wpr-816280

RESUMEN

One of the new requirements for modern standardized management in obsterics is the use of ultrasound in the delivery room.Ultrasound can help clinicians to identify the fetal condition,fetal presentation and placental location,and the circumstances of uterine and abdominal cavity quickly and accurately in managing obstetric emergencies.It can also guide the management of labour progress,the selection of suitable mode of delivery,the appropriate operation to assist delivery,and the interventional operations. In recent years,there have been many progresses in the application of ultrasound in the labor ward,such as new indicators for the evaluation of labor progressing with ultrasonic,ultrasound-guided anesthesia and tracheal intubation,and evaluation of cardiac volume load and cardiac function and so on.So it can provide further protection for maternal and infant safety.

9.
Chinese Journal of Pathophysiology ; (12): 260-266, 2019.
Artículo en Chino | WPRIM | ID: wpr-744237

RESUMEN

AIM:To investigate the effect of CUDC-907, a dual histone deacetylase (HDAC) and phosphatidylinositol 3-kinase (PI3K) inhibitor, on the DNA damage, cell cycle distribution and autophagy in human glioma U251cells.METHODS:U251 cells were treated with CUDC-907 of different concentrations, and the cell viability was detected by MTT assay.The quantitativeγ-H2AX foci were determined by laser scanning confocal microscopy.The cell cycle distribution of U251 cells was examined by flow cytometry.The protein expression was determined by Western blot analysis.RESULTS:CUDC-907 inhibited the cell viability and the phosphorylation of Akt and p70 ribosomal protein S6 kinase (p70s6K) in the U251 cells (P<0.05).In CUDC-907-treated cells, the number ofγ-H2AX foci and protein expression ofγ-H2AX were increased significantly (P<0.05).CUDC-907 also induced cell arrest in theM phase by up-regulating the expression of p21, and inhibiting the protein level of cyclin B1 and the phosphorylation of cell division cycle protein2 (Cdc2).In addition, CUDC-907 triggered cell autophagy, and inhibition of autophagy increased CUDC-907-induced DNA damage of U251 cells.CONCLUSION:CUDC-907 significantly inhibits PI3K/Akt signaling pathway, induces DNA damage and arrests cell cycle inM phase.Blockage of autophagy promotes CUDC-907-induced DNA damage of U251cells.

10.
Journal of Zhejiang University. Science. B ; (12): 610-619, 2018.
Artículo en Inglés | WPRIM | ID: wpr-1010398

RESUMEN

A transgenic maize event ZD12-6 expressing a Bacillus thuringiensis (Bt) fusion protein Cry1Ab/Cry2Aj and a modified 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) protein G10 was characterized and evaluated. Southern blot analysis indicated that ZD12-6 is a single copy integration event. The insert site was determined to be at chromosome 1 by border sequence analysis. Expression analyses of Bt fusion protein Cry1Ab/Cry2Aj and the EPSPS protein G10 suggested that they are both expressed stably in different generations. Insect bioassays demonstrated that the transgenic plants are highly resistant to Asian corn borer (Ostrinia furnacalis), cotton boll worm (Helicoverpa armigera), and armyworm (Mythimna separata). This study suggested that ZD12-6 has the potential to be developed into a commercial transgenic line.


Asunto(s)
Animales , 3-Fosfoshikimato 1-Carboxiviniltransferasa/metabolismo , Toxinas de Bacillus thuringiensis , Proteínas Bacterianas/metabolismo , China , Resistencia a la Enfermedad/genética , Resistencia a Medicamentos/genética , Endotoxinas/metabolismo , Perfilación de la Expresión Génica , Glicina/química , Proteínas Hemolisinas/metabolismo , Insectos , Enfermedades de las Plantas/prevención & control , Plantas Modificadas Genéticamente/genética , Zea mays/genética , Glifosato
11.
Basic & Clinical Medicine ; (12): 512-515, 2018.
Artículo en Chino | WPRIM | ID: wpr-693932

RESUMEN

Objective To investigate the relation between expression of JARID1B/KDM5B in invasive breast cancer tissue and circulating tumor cells of invasive breast patients. Methods The S-P immunohistochemical method was used to observe the expression of JARID1B/KDM5B in lesions.imFISH method was used to detect circulation tumor cells. Results Twenty-seven cases of patients showed CTC positive(the number of CTC was more than or equal to 2) in 35 invasive breast cancer cases,The results of JARID1B/KDM5B expression were as follows:(-) (n=0) and (+) in 1 case,(++) in 3 cases,(+++) in 23 cases,8 cases of negative cases (the number of CTC < 2), JARID1B/KDM5B immune group of results:(-) (n=2),(+) in 2 cases,(++) in 1 case,(+++) in 3 cases, The positive relation was found in expression of JARID1B/KDM5B and circulating tumor cells(P<0.05). Conclu-sions JARID1B/KDM5B positive expression in tumor tissues has a certain significance in predicting the recurrence and metastasis of tumor.

12.
Journal of Sun Yat-sen University(Medical Sciences) ; (6): 349-355, 2018.
Artículo en Chino | WPRIM | ID: wpr-712958

RESUMEN

[Objective] To investigate the molecular mechanism of miR-192/-215 targeting BIVM in human gastric cancer.[Methods] First,BIVM was the target gene of miR-192/-215 screened by the target gene prediction in solico and gene microarrays.Real-time quantitative PCR verified the results of the microarrays.Then the double-luciferase reporter plasmids were constructed to test that BIVM was the target gene of miR-192/-215.Subsequently,BIVM-siRNA was transfected,to know the effects of BIVM-siRNA on proliferation and apoptosis of gastric cancer cells.8 nude mice were randomly divided into two groups:BIVM-siRNA experimental group and NSC-siRNA control group.Gastric cancer cells transfected with BIVM-SiRNA were implanted under the skin of nude mice to observe the effect of BIVM on the tumorigenicity of gastric cancer cells.[Results] BIVM was screened as miR-192/-215 target gene by gene microarrays and quantitative PCR.Double-luciferase reporting assays were performed to identify the BIVM as miR-192/-215 target gene.The cell proliferation assays showed that BIVM promoted the proliferation of gastric cancer cells (P<0.05).Test of flow cytometry showed that BIVM inhibited the apoptosis of gastric cancer cells (P<0.05).Mouse tumorigenesis test confirmed that BIVM could promote gastric cancer cells growth in vivo (P<0.05).[Conclusion] BIVM plays a role in the carcinogenesis of gastric cancer,and miR-192/-215 targeting BIVM promotes the development of gastric cancer.

13.
Journal of Preventive Medicine ; (12): 360-362, 2017.
Artículo en Chino | WPRIM | ID: wpr-792614

RESUMEN

Objective This study was conducted to determine the prognostic factors of cervical adenocarcinoma.Methods Between July 2008 and June 2013, 211 consecutive patients were treated because of International Federation of Gynecology and Obstetrics(FIGO) stage IA-IVB cervical adenocarcinoma.Overall survival was analyzed by the Kaplan-Meier method.Results One-year OS rate was 96.2%,and 3-year OS rate was 88.6%,and 5-year OS rate was 74.7%.Patients'age,FIGO stage,postoperative clinicopathological factors such as depth of stromal invasion,number of pelvic lymph node metastasis and para-aortic lymph node metastasis,were analyzed to discriminate their prognostic role.In the univariate analysis, age,FIGO stge,deep stromal invasion, lymph-vascular space invasion, number of pelvic lymph node metastasis,para-aortic lymph node metastasis were associated with poorer survival(P< 0.05).In the cox analysis, age (RR=4.940,95%CI:1.925-12.678),pelvic lymph node metastasis(RR=2.391,95%CI:1.311-4.360),para-aortic lymph node metastasis (RR=6.344,95%CI:1.007-39.990)and FIGO stage(Ⅲ vs I,RR=5.315,95%CI:2.760-12.203;Ⅳ vs I,RR=9.932,95%CI:2.905-18.846)were independent prognostic factors of invasive cervical adenocarcinoma.Conclusion Early detection and early treatment is very important for cervical adenocarcinoma patients.Give the patient suitable and maybe more aggressive adjuvant therapy according to surgical pathology is helpful for imporving adenocarcinoma treatment.

14.
China Journal of Chinese Materia Medica ; (24): 4631-4635, 2017.
Artículo en Chino | WPRIM | ID: wpr-338226

RESUMEN

This paper describes a study exploring the interaction between gomizine D and α-glucosidase. The inhibitory activity of α-glucosidase by gomizine D was determined using PNPG as substrates Gomizine D gave the IC₅₀ value of 0.59 mmol•L⁻¹, which was higher than that of acarbose (1.95 mmol•L⁻¹). Gomizine D was a reversible and non-competitiveα-glucosidase inhibitor with an inhibition constant Ki=4.026 g•L⁻¹. The binding mode between gomizine D and α-glucosidase was analyzed by AutoDock Vina molecular docking software. The lowest energy of Gomizine D binding to α-glucosidase was -7.7 kcal•mol⁻¹, which was lower than that of acarbose (-6.6 kcal•mol⁻¹). After binding with gomizine D, UV spectroscopy analysis displayed that the microenvironment of aromatic residue in the secondary structure of α-glucosidase was changed, and the polarity of protein was reduced.

15.
China Journal of Chinese Materia Medica ; (24): 4355-4358, 2015.
Artículo en Chino | WPRIM | ID: wpr-279234

RESUMEN

Peroxisome proliferator-activated receptors (PPARs) are nuclear transcriptional factors closely related to glucose and lipid metabolism, insulin sensitivity. Activation of PPARs targets treated type 2 diabetes, obesity, hypertension and other metabolic diseases by insulin resistance. Recently, a variety of active ingredients of traditional Chinese medicines (TCMs) have been proved to activate PPARs targets for improving insulin resistance, which has attracted widespread attention at home and abroad. In this paper, we reviewed the pathological mechanisms between insulin resistance and PPARs, and summarized the active ingredients of TCMs improved insulin resistance based on PPARs targets. This paper may provide some theoretical guidance for the development of new drugs and TCMs.


Asunto(s)
Animales , Humanos , Medicamentos Herbarios Chinos , Farmacología , Resistencia a la Insulina , Enfermedades Metabólicas , Quimioterapia , Genética , Metabolismo , Receptores Activados del Proliferador del Peroxisoma , Genética , Metabolismo
16.
Acta Pharmaceutica Sinica ; (12): 419-426, 2014.
Artículo en Chino | WPRIM | ID: wpr-245067

RESUMEN

To study the antiarrhythmic effect of the newly developed alpha/beta-blocker TJ0711, a variety of animal models of arrhythmia were induced by CaCl2, ouabain and ischemia/reperfusion. Glass microelectrode technique was used to observe action potentials of right ventricular papillary muscle of guinea pig. The onset time of arrhythmia induced by CaCl2 was significantly prolonged by TJ0711 at 0.75, 1.5 and 3 mg x kg(-1) doses. TJ0711 (1.5 and 3 mg x kg(-1)) can significantly shorten the ventricular tachycardia (VT) and ventricular fibrillation (VF) duration, the incidence of VF and mortality were significantly reduced. On ischemia-reperfusion-induced arrhythmic model, TJ0711 (0.25, 0.5, 1 and 2 mg x kg(-1)) can significantly reduce the ventricular premature contraction (PVC), VT, VF incidence, mortality, arrhythmia score with a dose-dependent manner. At the same time, rats serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities decreased significantly by TJ0711 (1 and 2 mg x kg(-1)). Ouabain could cause arrhythmia in guinea pigs, when TJ0711 (0.375, 0.75, 1.5 and 3 mg x kg(-1)) was given, the doses of ouabain inducing a variety of arrhythmia PVC, VT, VF, cardiac arrest (CA) were significantly increased with a dose-dependent manner. In the TJ0711 0.1-30 micromol x L(-1) concentration range, guinea pig right ventricular papillary muscle action potential RP (rest potential), APA (action potential amplitude) and V(max) (maximum velocity of depolarization) were not significantly affected. APD20, APD50 and APD90 had a shortening trend but no statistical difference with the increase of TJ0711 concentration. TJ0711 has antiarrhythmic effect on the sympathetic nerve excitement and myocardial cell high calcium animal arrhythmia model. Myocardial action potential zero phase conduction velocity and resting membrane potential were not inhibited by TJ0711. APD20, APD50 and APD90 were shortened by TJ0711 at high concentration. Its antiarrhythmic action mechanism may be besides the action of blocking beta1 receptor, may also have a strong selective blocking action on alpha1 receptor and reducing intracellular calcium concentration.


Asunto(s)
Animales , Femenino , Masculino , Ratas , Potenciales de Acción , Antagonistas Adrenérgicos alfa , Farmacología , Antagonistas Adrenérgicos beta , Farmacología , Antiarrítmicos , Farmacología , Arritmias Cardíacas , Sangre , Patología , Cloruro de Calcio , Creatina Quinasa , Sangre , Relación Dosis-Respuesta a Droga , Cobayas , Ventrículos Cardíacos , Biología Celular , Lactato Deshidrogenasas , Sangre , Daño por Reperfusión Miocárdica , Miocitos Cardíacos , Fisiología , Ouabaína , Músculos Papilares , Biología Celular , Fenoxipropanolaminas , Farmacología , Distribución Aleatoria , Ratas Sprague-Dawley
17.
China Journal of Chinese Materia Medica ; (24): 1157-1162, 2014.
Artículo en Chino | WPRIM | ID: wpr-321346

RESUMEN

Four different extracts of Oxytropis falcata, including the aerial aqueous extract, and the underground aqueous extract, the aerial lipophilic extract, and the underground lipophilic extract were prepared and then administrated orally to mice at the maximum dose (50 g x kg(-1) x d(-1) calculated by raw material) for fifteen days respectively. Compared with the control group, which was administrated of 1.0% tween-80, the treatment groups did not show significant differences in appearance and behavior. However, the organcoefficient, blood biochemical indicator and pathological section results showed that the lipophilic extracts of the aerial and underground parts of O. flacata showed mild injury to the liver of mice, while the aerial and underground aqueous extracts and the underground lipophilic extract showed mild toxicity to the kidney of male mice. Chemical analysis showed that the lipophilic extracts of the aerial and underground parts, especially aerial lipophilic extract, consisted of large amount of flavonoid aglycones with little amount of polysaccharides and proteins, while the aqueous extracts contained much polysaccharides and proteins with almost no flavonoid aglycones detected.


Asunto(s)
Animales , Femenino , Masculino , Ratones , Peso Corporal , Hígado , Medicina Tradicional Tibetana , Estructura Molecular , Tamaño de los Órganos , Oxytropis , Química , Extractos Vegetales , Química , Toxicidad , Espectrometría de Masa por Ionización de Electrospray
18.
Chinese Journal of Oncology ; (12): 181-186, 2013.
Artículo en Chino | WPRIM | ID: wpr-284212

RESUMEN

<p><b>OBJECTIVE</b>To study the molecular mechanism of epidermal growth factor receptor (EGFR) signaling pathway in mediating paclitaxel-resistance and improving paclitaxel sensitivity in human melanoma A375 cells.</p><p><b>METHODS</b>Human melanoma cell line A375 cells were treated with different concentrations of paclitaxel with or without 20 µmol/L AG1478 (EGFR inhibitor), 40 µmol/L PD98059 (extracellular signal conditioning kinase (ERK) 1/2 blockers) or 10 µmol/L LY294002 (PI3K inhibitor). MTT method was used to measure the proliferation of A375 cells. Flow cytometry was used to detect cell cycle and apoptosis in the A375 cells. The expressions of P-EGFR, P-ERK and P-AKT proteins were determined by Western blot analysis.</p><p><b>RESULTS</b>Paclitaxel (0.001 µmol/L to 0.1 µmol/L) inhibited the growth of A375 cells (P < 0.01) and induced apoptosis (P < 0.05) in a dose- and time-dependent manner. AG1478 (20 µmol/L) increased the 0.01 µmol/L paclitaxel-induced inhibition rate from 38.5% to 62.6% at 72 h. Different doses of paclitaxel induced apoptosis in A375 cells by different ways, in which G0/G1 phase cells were decreased and mitotic phase was prolonged at 0.01 µmol/L, and cell cycle arrest at G2/M phase by 0.1 µmol/L paclitaxel. When DNA damage occurred in A375 cells exposed to paclitaxel, expression of P-EGFR, P-ERK and P-AKT proteins was increased. When EGFR signaling pathway was blocked, paclitaxel did not activate MAPK signaling pathway or PI3K/AKT signaling pathway and did not change its effect on cell cycle in vitro. When EGFR was inhibited by 20 µmol/L tyrophostin AG1478, the 0.001 and 0.01 µmol/L paclitaxel-induced early apoptosis rate in A375 cells was increased by 1.73- and 1.80-fold, respectively. When the ERK signaling was blocked by 40 µmol/L PD98059, the 0.001 and 0.01 µmol/L paclitaxel-induced early apoptosis rate in A375 cells was increased by 2.73- and 2.25-fold, respectively. When the AKT signaling was blocked by 10 µmol/L LY294002, the 0.001 and 0.01 µmol/L paclitaxel-induced early apoptosis rate in A375 cells was increased by 2.02- and 1.46-fold, respectively.</p><p><b>CONCLUSIONS</b>Human melanoma A375 cells produce resistance to paclitaxel (0.001 to 0.1 µmol/L) by activating MAPK signaling and PI3K/AKT signaling pathways. Targeting EGFR, ERK and AKT signaling pathways significantly enhances the cytotoxic effect of paclitaxel on human melanoma cells.</p>


Asunto(s)
Humanos , Antineoplásicos Fitogénicos , Farmacología , Apoptosis , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Cromonas , Farmacología , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos , Quinasas MAP Reguladas por Señal Extracelular , Metabolismo , Flavonoides , Farmacología , Melanoma , Metabolismo , Patología , Morfolinas , Farmacología , Paclitaxel , Farmacología , Fosfatidilinositol 3-Quinasas , Metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt , Metabolismo , Quinazolinas , Farmacología , Receptores ErbB , Metabolismo , Transducción de Señal , Tirfostinos , Farmacología
19.
Chinese Journal of Industrial Hygiene and Occupational Diseases ; (12): 730-734, 2012.
Artículo en Chino | WPRIM | ID: wpr-324175

RESUMEN

<p><b>OBJECTIVE</b>To investigate the effect of lead exposure on the gene expression of fibroblast growth factor 3 (Fgf3) in zebrafish embryonic development and the mechanism of lead-induced embryonic developmental toxicity.</p><p><b>METHODS</b>The embryos of zebrafish (wild types A and B) were exposed to lead acetate (PbAc) at the doses of 0, 0.1, 0.5, 2.5, and 12.5 µmol/L separately. Total RNA was extracted from each treatment group of zebrafish embryos at 8, 12, 16, 24, 36, 48, and 72 hours post fertilization (hpf). The total mRNA expression of Fgf3 was measured by real-time quantitative PCR. The spatial expression of Fgf3 in zebrafish embryos was determined by whole-mount in situ hybridization using synthesized Fgf3 RNA probe.</p><p><b>RESULTS</b>The mRNA expression of Fgf3 in each group peaked at 12 hpf (P < 0.01). With the increase in PbAc concentration, the mRNA expression of Fgf3 rose. Compared with the mRNA expression level of Fgf3 in the control group, the relative mRNA expression levels of Fgf3 in the 0.1, 0.5, 2.5, and 12.5 µmol/L PbAc exposure groups were 1.02 ± 0.24, 1.05 ± 0.26, 1.22 ± 0.46, and 1.25 ± 0.38, respectively, and the 2.5 and 12.5 µmol/L PbAc exposure groups showed significantly higher Fgf3 expression than the control group (P < 0.05). The whole-mount in situ hybridization results showed that Fgf3 expression occurred mainly in the head and tail in the early stage of embryonic development and in the midbrain, fin bud, and pharyngeal arch in the middle/late stage of embryonic development; there were the most significant regions and intensities of positive hybridization signals at 12 hpf; but no significant differences were found between the control group and exposure groups in the location and intensity of Fgf3 expression</p><p><b>CONCLUSION</b>Lead exposure can result in the upregulation of Fgf3 expression in zebrafish embryonic development, which might contribute to lead-induced embryonic developmental toxicity.</p>


Asunto(s)
Animales , Desarrollo Embrionario , Factor 3 de Crecimiento de Fibroblastos , Genética , Metabolismo , Expresión Génica , Compuestos Organometálicos , Transducción de Señal , Pez Cebra , Embriología , Genética , Metabolismo , Proteínas de Pez Cebra , Genética , Metabolismo
20.
Chinese Journal of Medical Genetics ; (6): 103-107, 2011.
Artículo en Chino | WPRIM | ID: wpr-326981

RESUMEN

<p><b>OBJECTIVE</b>To investigate the polymorphisms of 9 non-DNA combined index system (CODIS) short tandem repeats (STRs), i.e., D7S3048, D8S1132, D11S2368, D2S1772, D6S1043, D13S325, D12S391, GATA198B05, D18S1364 in Hebei Han population, and evaluate the usage of them in paternity testing.</p><p><b>METHODS</b>One hundred and forty-seven unrelated healthy individuals from the Han population of Hebei province were genotyped using STRtyper10G kit including 9 STR loci on ABI 3130 Genetic Analyzer. Hardy-Weinberg equilibrium and population genetic parameters were calculated. Fourteen cases of motherless paternity testing and 2 cases of standard trios with mutation in 1 locus were detected using STRtyper10G.</p><p><b>RESULTS</b>(1) Ninety-nine alleles and 336 genotypes were observed in the 9 STR loci in the population. The cumulative discrimination power(DP) was higher than 0.999,999,999. The cumulative probability of exclusion (PE) for trios and duos were 0.999,974 and 0.998,759 respectively. Departure from Hardy-Weinberg equilibrium was not observed in any of the 9 loci. (2) The combined paternity index (PI) of the 14 cases of motherless paternity testing ranged from 10³-10⁶ for 15 STR loci in ID, whereas it reached 10⁵-10⁹ for 22 independent STR loci included in ID and STRtyper 10G. Possible mutation in FGA and vWA was observed in 2 cases of trios, and the combined PI was 5945 and 1840 respectively for 15 STR loci in ID. Adding STRtyper 10G to detect these 2 cases, the combined PI reached 2.76 × 10⁷ and 4.88 × 10⁷ respectively.</p><p><b>CONCLUSION</b>The genetic polymorphism of the 9 non-CODIS STR loci included in STRtyper 10G was quite high in Chinese Hebei Han population, indicating the 9 STR loci are valuable as complement markers for ID and PP16 kit in motherless paternity testing, paternity testing with mutation and other kinds of complicated paternity testing.</p>


Asunto(s)
Humanos , China , Etnología , Frecuencia de los Genes , Genética de Población , Repeticiones de Microsatélite , Mutación , Paternidad , Polimorfismo Genético
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