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1.
Acta Physiologica Sinica ; (6): 390-402, 2023.
Article in Chinese | WPRIM | ID: wpr-981015

ABSTRACT

Heart failure with preserved ejection fraction (HFpEF) is a type of heart failure characterized by left ventricular diastolic dysfunction with preserved ejection fraction. With the aging of the population and the increasing prevalence of metabolic diseases, such as hypertension, obesity and diabetes, the prevalence of HFpEF is increasing. Compared with heart failure with reduced ejection fraction (HFrEF), conventional anti-heart failure drugs failed to reduce the mortality in HFpEF due to the complex pathophysiological mechanism and multiple comorbidities of HFpEF. It is known that the main changes of cardiac structure of in HFpEF are cardiac hypertrophy, myocardial fibrosis and left ventricular hypertrophy, and HFpEF is commonly associated with obesity, diabetes, hypertension, renal dysfunction and other diseases, but how these comorbidities cause structural and functional damage to the heart is not completely clear. Recent studies have shown that immune inflammatory response plays a vital role in the progression of HFpEF. This review focuses on the latest research progress in the role of inflammation in the process of HFpEF and the potential application of anti-inflammatory therapy in HFpEF, hoping to provide new research ideas and theoretical basis for the clinical prevention and treatment in HFpEF.


Subject(s)
Humans , Heart Failure , Stroke Volume/physiology , Hypertrophy, Left Ventricular/metabolism , Ventricular Dysfunction, Left/metabolism , Inflammation/complications , Obesity , Hypertension
2.
International Journal of Cerebrovascular Diseases ; (12): 912-916, 2022.
Article in Chinese | WPRIM | ID: wpr-989173

ABSTRACT

Objective:To investigate the predictive value of triglyceride-glucose (TyG) index for the overall burden of cerebral small vessel disease (CSVD).Methods:Consecutive patients with CSVD admitted to Jiaxing First Hospital from July 2019 to January 2021 were enrolled. MRI was used to conduct the overall burden score of CSVD. The difference of TyG index and other risk factors between high burden group (3-4 points) and low burden group (0-2 points) was analyzed. The independent predictors of the high burden of CSVD were determined by the multivariate logistic regression analysis, and the predictive value of TyG index for the high burden of CSVD was evaluated by the receiver operating characteristic (ROC) curve. Results:A total of 165 patients with CSVD were enrolled, including 103 patients (62.4%) in the low burden group and 62 (37.6%) in the high burden group. The proportion of patients with previous stroke or transient ischemic attack, as well as age, fasting blood glucose, glycosylated hemoglobin and TyG index in the high burden group were significantly higher than those in the low burden group ( P<0.05). Multivariate logistic regression analysis showed that TyG index (odds ratio [ OR] 4.584, 95% confidence interval [ CI] 2.180-8.887; P=0.001) and age ( OR 1.075, 95% CI 1.025-1.128; P=0.003) were the independent predictors of high burden of CSVD. The ROC curve showed that the area under the curve of TyG index for predicting the high burden of CSVD was 0.69 (95% CI 0.60-0.77). The optimal cutoff value was 8.5, and its sensitivity and specificity for predicting the high burden of CSVD were 72.6% and 64.1%, respectively. Conclusion:TyG index is associated with the overall burden of CSVD and has certain predictive value for the high burden of CSVD.

3.
Chinese journal of integrative medicine ; (12): 524-530, 2022.
Article in English | WPRIM | ID: wpr-939771

ABSTRACT

OBJECTIVE@#To explore the mechanisms underlying the proliferative inhibition of Chinese herbal medicine Kang-Ai injection (KAI) in gastric cancer cells.@*METHODS@#Gastric cancer cell lines MGC803 and BGC823 were treated by 0, 0.3%, 1%, 3% and 10% KAI for 24, 48 and 72 h, respectively. The cell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The apoptosis and cell cycle were evaluated by flow cytometry. Interleukin (IL)-6 mRNA and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA), respectively. The protein expression levels of cyclin A, cyclin E, cyclin B1, cyclin D1, p21, retinoblastoma (RB), protein kinase B (AKT), extracellular regulated protein kinases (ERK), signal transducer and activator of transcription (STAT) 1 and STAT3 were detected by Western blot.@*RESULTS@#KAI inhibited the proliferation of MGC803 and BGC823 gastric cancer cells in dose- and time-dependent manner. After treated with KAI for 48 h, the proportion of G1 phase was increased, expression level of cyclin D1 and phosphorylation-RB were down-regulated, whereas the expression of p21 was up-regulated (all P<0.01). Furthermore, 48-h treatment with KAI decreased the phosphorylation level of STAT3, inhibited the mRNA and protein expressions of IL-6 (all P<0.01). IL-6 at dose of 10 ng/mL significantly attenuated the proliferative effect of both 3% and 10% KAI, and recovered KAI-inhibited STAT3 phosphorylation and cyclin D1 expression level (all P<0.01).@*CONCLUSION@#KAI exerted an anti-proliferative function by inhibiting IL-6/STAT3 signaling pathway followed by the induction of G1 phase arrest in gastric cancer cells.


Subject(s)
Humans , Apoptosis , Cell Line, Tumor , Cell Proliferation , Cyclin D1/pharmacology , Interleukin-6/metabolism , RNA, Messenger/metabolism , STAT3 Transcription Factor/metabolism , Stomach Neoplasms/genetics
4.
Acta Anatomica Sinica ; (6): 55-59, 2021.
Article in Chinese | WPRIM | ID: wpr-1015517

ABSTRACT

Objective To construct the recombinant plasmids of knocking down Rho guanine dissociation inhibitor α (GDIα ) gene by using clustered regularly interspaced short palindromic repeats/associated protein 9 (CRISPR/Cas9) technique, and investigate the effect of Rho GDIα interference on the migration of Hepa 1-6 cells of mouse in order to provide the method of prevention and treatment of liver cancer. Methods To construct and identify the PX458-Rho GDIα-single guide (sg) RNAs by using CRISPR/Cas9 technique. And the Hepa 1-6 cells were transfected by liposomes with PX458-Rho GDIα-sgRNAs for 48 hours respectively, and cells treated with PX458 plasmids were used as control. The migration ability of Hepa 1-6 was checked by wound healing assay and Transwell assay, respectively. Results The expression of Rho GDIα was depressed in group of PX458-Rho GDIα-sgRNAl transfection which was detected by using RT-PCR. The migration distance of Hepa 1-6 in PX458-Rho GDIα-sgRNAl transfection group was significantly promoted comparing with the control group which was transfected with PX458 only, and the cell number of PX458-Rho GDIα-sgRNAl group was more than that in control group by using transwell assay, indicating concluded that knocking down of Rho GDIα promoted the migration ability of Hepal-6 cells. Conclusion The result is explicit that in vivo, Rho GDIα may inhibit the migration of Hepal-6 partially. Overexpression of Rho GDIα might be used as an important method to prevent the metastasize of carcinoma.

5.
Acta Anatomica Sinica ; (6): 231-235, 2021.
Article in Chinese | WPRIM | ID: wpr-1015475

ABSTRACT

Objective To construct the clustered regularly interspaced short palindromic repeats / associated protein 9 (CRISPR/ Cas9) plasmid targeting forkhead box J2 (FOXJ2) gene and investigate the effects of FOXJ2 interference on the expression of transforming growth factor-β(TGF-β) / Smads and proliferation in hepatocellular carcinoma cells of mouse. Methods Small guide RNA(sgRNA) sequence of FOXJ2 was designed, linked with PX458 vector and transfected into competent E. coli for proliferation. The recombinant plasmids were sent for sequencing to confirm the accuracy of the sgRNA sequence. The PX458-FOXJ2-sgRNAs plasmids were transfected into Hepa1-6 cells by liposome transfection, respectively. The empty vectors of PX458 were transfected as control group. After 48 hours, the expression of FOXJ2, TGF-β and Smads were obtained by RT-PCR and agarose gel electrophoresis, respectively. The cell proliferation was detected by methylthio tetrazole (MTT) method . Results The CRISPR/ Cas9 plasmids of PX458-FOXJ2-sgRNAs were successfully constructed. The recombinant plasmid of PX458-FOXJ2-sgRNA2 could effectively inhibit FOXJ2 gene expression which induced increasing expression of TGF-β, Smad2 and Smad4 in Hepa1-6 cells comparing to the control group transfected with PX458 only. And the proliferation of Hepa1-6 was promoted in PX458-FOXJ2-sgRNA2 interference group. Conclusion In hepatocellular carcinoma cells of mouse, FOXJ2 gene inhibits the expression of TGF-β, Smad2, Smad4 and cell proliferation partially, which indicates the relationship between FOXJ2 and TGF-β signal pathway. The result provides the target molecule of FOXJ2 for the prevention and treatment of hepatocellular carcinoma.

6.
Journal of Experimental Hematology ; (6): 1929-1934, 2021.
Article in Chinese | WPRIM | ID: wpr-922226

ABSTRACT

OBJECTIVE@#To explore the role and significance of blood group genotyping and gene sequencing technology in the identification of blood group subtypes.@*METHODS@#Blood type of the proband and his son were identified by blood type serology, and ABO genotyping and DNA sequencing were performed according to the results of serological expression pattern.@*RESULTS@#The weak B antigen expression was found in the proband and his son by serological test, and was preliminarily identified as B3 subtype. The ABO blood group genotyping confirmed that the genotype of the proband and his son was B/O1 and B/O2, respectively. Finally, through gene sequencing, it was confirmed that the B101 allele of the proband and his son showed a heterozygous mutation of 5873CT.@*CONCLUSION@#The combination of serology, genotyping and sequencing showed find new blood group gene mutation sites, which is important strategic significance for accurate blood group identification, personalized blood use and trasfusion safety, which is beneficial to clarify the molecular biological basis of ABO blood group subtypes.


Subject(s)
Humans , ABO Blood-Group System/genetics , Alleles , Genotype , Mutation , Sequence Analysis, DNA
7.
West China Journal of Stomatology ; (6): 102-105, 2019.
Article in Chinese | WPRIM | ID: wpr-772690

ABSTRACT

Epigenetics is defined as a change in gene expression without the alteration of the genetic sequence. Such a change would be inherited by offspring. Histone acetylation is a type of epigenetics. Existing studies proposed that chronic periodontitis is related to epigenetic modification. In this review, we summarised the influence of chronic periodontitis on periodontal ligament stem cells by histone acetylation.


Subject(s)
Acetylation , Cell Differentiation , Cells, Cultured , Histones , Metabolism , Osteogenesis , Periodontal Ligament , Stem Cells , Physiology
8.
Chinese Journal of Clinical and Experimental Pathology ; (12): 14-18, 2019.
Article in Chinese | WPRIM | ID: wpr-743332

ABSTRACT

Purpose To investigate the value of application of D2-40/CD34-CK cocktail antibodies by double immunohistochemical staining for assessment of lymphovascular invasion (LVI) and to determine its prognostic significance in colorectal cancer with insufficient lymph node harvest. Methods Specimens from 133 cases of colorectal cancer with less than 12 lymph nodes were selected. HE staining and double immunohistochemical staining of the cocktail antibodies were performed to compare the difference of the two methods in screening for LVI. The The relationship between LVI confirmed by cocktail antibody immunohistochemical staining and clinicopathological characteristics and overall survival (OS) of patients was analyzed. Results (1) The detection rates of cocktail antibody double immunohistochemical staining and HE staining for LVI were 42.9% (57/133) and 21.8% (29/133) with statistically significant difference (P < 0.001). (2) The presence of LVI confirmed by double staining was significantly associated with Dukes staging, depth of invasion, clinical stages, lymph node metastasis and tumor budding (P < 0.05). (3) The presence of LVI, the location and extent of LVI, and the number of tumor cells in thrombus ≥5.5 for cases with LVI ≤2 clusters, were significantly associated with OS (P < 0.05). Conclusion D2-40/CD34-CK cocktail antibodies double staining is superior to routine HE staining in assessing LVI. LVI is intimately associated with tumor stage, lymph nodes metastasis and tumor budding, and it is an independent prognostic factor for CRC patients. It should be a supplementary examination for these patients with insufficient lymph node harvest.

9.
Chinese Journal of Infection Control ; (4): 1019-1021,1025, 2018.
Article in Chinese | WPRIM | ID: wpr-701640

ABSTRACT

Objective To understand the status of hand hygiene(HH)of health care workers(HCWs)in a tertiary hospital in Zhuhai.Methods HH compliance of doctors,nurses,and cleaners randomly selected from 15 clinical de-partments in the whole hospital was observed through concealed observation by medical interns in October-Novem-ber 2016.Results HH compliance rate and correct rate of clinical departments in the whole hospital were 33.44%(1 131/3 382)and 59.86%(677/1 131)respectively,there was a significant difference in the compliance rate of HH among different types of HCWs (χ2 =12.610,P=0.002),HH compliance rate from high to low was nurses (35.85%),cleaners (32.28%),and doctors (29.50%).Of five HH moments,HCWs’HH compliance rate after patient’s body fluid exposure was the highest (69.74%),while after touching patient surroundings was the worst (25.03%).HH compliance rates of HCWs with different occupations at different HH moments were all significant-ly different (all P<0.05),HH compliance rates of doctors before aseptic procedure and after patient’s body fluid exposure were higher than nurses(71.25% vs 32.44%;82.86% vs 69.78%,respectively),HH compliance rate of nurses was highest after touching a patient(40.06%).Conclusion HH status in this hospital is not optimistic,HH compliance rate and correct rate are low,HH compliance rates of HCWs with different occupations and at different HH moments are both different,which need to be improved.

10.
Basic & Clinical Medicine ; (12): 610-615, 2018.
Article in Chinese | WPRIM | ID: wpr-693951

ABSTRACT

Objective To investigate the effect of hypoxia on the expression of IL-1βin macrophages.Methods RAW264.7 cells were treated with normoxia(21%O2),hypoxia(2%O2), normoxia(21%O2)plus LPS and hypoxia(2%O2)plus LPS.RT-qPCR was used to detect the mRNA expression of Vegf,Nlrp3 and Il1b.Western blot was used to detect the protein expression of HIF-1α,NLRP3,caspase-1,cleaved caspase-1,Pro-IL-1βand IL-1β.The peritoneal macrophages of Vhlfl/fl/Apoe-/-mice and VhlΔMac/Apoe-/-mice were treated with or without LPS.RT-qPCR was used to detect the mRNA expression of Vhl,Nlrp3,Il1b and Il6.Results Compared with nor-moxia, hypoxia significantly increased mRNA of Vegf, Nlrp3 and Il1b in RAW264.7(P<0.01).Hypoxia increased mRNA and protein of NLRP 3 and IL-1βin RAW264.7 induced with LPS comparing with normoxia(P<0.01).Hypoxia had no effects on the activation of caspase-1 and the subsequent maturation of Pro-IL-1βinduced with LPS in RAW264.7.Compared with Vhlfl/fl/Apoe-/-peritoneal macrophages,VhlΔMac/Apoe-/-peritoneal macro-phages showed significantly increased mRNA levels of Nlrp3,Il1b and Il6 induced with LPS(P<0.05).Conclu-sions Hypoxia amplifies lipopolysaccharide-induced IL-1βexpression in macrophages.

11.
National Journal of Andrology ; (12): 17-22, 2015.
Article in Chinese | WPRIM | ID: wpr-319549

ABSTRACT

<p><b>OBJECTIVE</b>To explore the molecular mechanism of dutasteride inhibiting fertility by studying its effects on the expressions of the epididymal epithelial junction proteins Claudin1 and β-catenin in rats.</p><p><b>METHODS</b>Sixteen 3-month-old SD male rats were equally divided into an experimental and a negative control group to be treated intragastrically with dutasteride at 40 mg/kg per day and the same dose of solvent, respectively, for 14 consecutive days. Then, the sperm motility and morphology of the rats were detected by computer-assisted sperm analysis, the serum levels of testosterone (T) and dihydrotestosterone (DHT) measured by ELISA, changes in the tight junction of epididymal cells observed under the transmission electron microscope, the protein and gene expressions of Claudin1 and β-catenin determined by RT-PCR and immunohistochemistry, and the conception rate of the mated female rats calculated.</p><p><b>RESULTS</b>Dutasteride significantly suppressed the serum DHT level, sperm motility, and fertility of the rats (P <0.05). Interspaces between epididymal epithelial cell tight junctions were observed, the volume of epididymal fluid obviously increased, and the expressions of Claudin1 and β-catenin gene and protein remarkably downregulated in the experimental rats (P <0.05).</p><p><b>CONCLUSION</b>Dutasteride can significantly inhibit the fertility of male rats by reducing the serum DHT level, suppressing Claudin1 and β-catenin expressions, and damaging epididymal epithelial cell junctions.</p>


Subject(s)
Animals , Female , Humans , Male , Rats , Azasteroids , Pharmacology , Claudin-1 , Metabolism , Dihydrotestosterone , Blood , Dutasteride , Epididymis , Metabolism , Fertility , Intercellular Junctions , Rats, Sprague-Dawley , Sperm Motility , Testosterone , Blood , Urological Agents , Pharmacology , beta Catenin , Metabolism
12.
Biomedical and Environmental Sciences ; (12): 308-311, 2015.
Article in English | WPRIM | ID: wpr-264583

ABSTRACT

To evaluate the efficacy of changing grains on the prevention and treatment of Kashin-Beck Disease (KBD) in children, community-based trials were acquired from seven electronic databases (up to July 2014). As a result, the methodological quality of the six trials that have been included into our analysis was low. The pooled ORs favoring the prevention and treatment effects of changing grains were 0.15 (95% CI: 0.03-0.70) and 2.13 (95% CI: 1.44-3.16) respectively by meta-analysis. Subgroup analysis demonstrated the pooled OR favoring treatment effect of exchanging grains rather than drying grains both compared with endemic grains. The results showed that changing grains had obvious effects on the prevention and treatment of KBD in children. However, the evidences were limited by the potential biases and confounders. Large and well-designed trials are still needed.


Subject(s)
Adolescent , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Community-Based Participatory Research , Edible Grain , Physiology , Kashin-Beck Disease , Therapeutics
13.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 447-51, 2013.
Article in English | WPRIM | ID: wpr-636456

ABSTRACT

The purpose of this study was to evaluate the value of multi-detector computed tomography (MDCT) angiography for the diagnosis of congenital aortic arch anomalies and present the radiological images of congenital aortic arch anomalies in Chinese children. MDCT angiography and transthoracic echocardiography (TTE) were applied for the diagnosis of congenital aortic arch anomalies in 362 Chinese children between May 2006 and December 2011 (age ranges from 5 days to 12 years; mean age, 3.3 years). Surgery and/or catheter angiography (CA) were conducted in all patients to confirm the final diagnosis. In the 362 Chinese children with congenital heart anomalies, congenital aortic arch anomalies were definitely diagnosed in 198 children and 164 children ruled out by operation and/or (CA). Among the 198 children with anomalies, coarctation of aorta (CoA), interruption of aortic arch (IAA), right aortic arch, aberrant right subclavian artery and double aortic arch were diagnosed in 134, 32, 20, 10 and 2 children respectively, and there were 6 cases with uncommon congenital aortic arch anomalies: 2 had double aortic arch including 1 with five branches of the aortic arch, 2 had isolation of the right subclavian artery with two patent ductus arteriosus (PDA), 1 had an isolation of the common carotid artery with a PDA, and 1 had double PDA with a single ventricle and pulmonary artery atresia. Among the 32 children with IAA, 28 were of type A, and 4 were of type B. The diagnostic sensitivity, specificity and accuracy of MDCT angiography for congenital aortic arch anomalies were 100% (198/198), 98% (161/164) and 99% (359/362), respectively. The diagnostic sensitivity, specificity and accuracy of TTE were 92% (182/198), 81% (133/164) and 87% (315/362), respectively. In conclusion, MDCT angiography is a reliable, noninvasive imaging technique for the diagnosis of congenital aortic arch anomalies in children. Sometimes, even more information can be obtained from this technique than from conventional angiography.

14.
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 447-451, 2013.
Article in English | WPRIM | ID: wpr-251450

ABSTRACT

The purpose of this study was to evaluate the value of multi-detector computed tomography (MDCT) angiography for the diagnosis of congenital aortic arch anomalies and present the radiological images of congenital aortic arch anomalies in Chinese children. MDCT angiography and transthoracic echocardiography (TTE) were applied for the diagnosis of congenital aortic arch anomalies in 362 Chinese children between May 2006 and December 2011 (age ranges from 5 days to 12 years; mean age, 3.3 years). Surgery and/or catheter angiography (CA) were conducted in all patients to confirm the final diagnosis. In the 362 Chinese children with congenital heart anomalies, congenital aortic arch anomalies were definitely diagnosed in 198 children and 164 children ruled out by operation and/or (CA). Among the 198 children with anomalies, coarctation of aorta (CoA), interruption of aortic arch (IAA), right aortic arch, aberrant right subclavian artery and double aortic arch were diagnosed in 134, 32, 20, 10 and 2 children respectively, and there were 6 cases with uncommon congenital aortic arch anomalies: 2 had double aortic arch including 1 with five branches of the aortic arch, 2 had isolation of the right subclavian artery with two patent ductus arteriosus (PDA), 1 had an isolation of the common carotid artery with a PDA, and 1 had double PDA with a single ventricle and pulmonary artery atresia. Among the 32 children with IAA, 28 were of type A, and 4 were of type B. The diagnostic sensitivity, specificity and accuracy of MDCT angiography for congenital aortic arch anomalies were 100% (198/198), 98% (161/164) and 99% (359/362), respectively. The diagnostic sensitivity, specificity and accuracy of TTE were 92% (182/198), 81% (133/164) and 87% (315/362), respectively. In conclusion, MDCT angiography is a reliable, noninvasive imaging technique for the diagnosis of congenital aortic arch anomalies in children. Sometimes, even more information can be obtained from this technique than from conventional angiography.


Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Abnormalities, Multiple , Diagnostic Imaging , Aorta, Thoracic , Congenital Abnormalities , Diagnostic Imaging , Aortic Arch Syndromes , Diagnostic Imaging , Aortography , Methods , China , Multidetector Computed Tomography , Methods , Reproducibility of Results , Sensitivity and Specificity , Tomography, X-Ray Computed , Methods
15.
Chinese Journal of Otorhinolaryngology Head and Neck Surgery ; (12): 926-930, 2012.
Article in Chinese | WPRIM | ID: wpr-262443

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the detrimental effects of ouabain on cochlear spiral ganglion neurons (SGCs) in vivo and in vitro.</p><p><b>METHODS</b>Seventy-five male SD rats were randomly divided into 5 groups. In addition to the normal control group, rats in other 4 groups received 0.01, 0.02, 0.05 mmol/L of Ouabain or saline through cochlear scala tympani drilling. Seven days after surgery, the hearing threshold was measured by distortion product otoacoustic emissions (DPOAE) and auditory brainstem response (ABR) in rats. In the in vitro study, SGNs were isolated from SD rats (E14) and treated with 1 × 10(-8) mmol/L of Ouabain. The damaged of SGCs were detected after ouabain treatment using immunohistochemistry, transmission electron microscope and scanning electron microscope in vitro.</p><p><b>RESULTS</b>After administration of Ouabain, DPOAE did not change significantly. No significant difference in the amplitude of DPOAE could be observed among all the groups (P > 0.05). Compared with saline and normal control, ABR threshold was significantly increased in the Ouabain treated groups (P < 0.05), which correlated with the concentration of Ouabain. Electron microscopy showed that after treated with Ouabain, SGCs presented degenerative changes, including collapse of organelle structures, the karyotheca dissolved, myelin sheath disintegrating. Ouabain could damage type I SGCs but not type II SGNs.</p><p><b>CONCLUSIONS</b>Ouabain can damage SGCs, either in the in vivo or in vitro conditions.</p>


Subject(s)
Animals , Male , Rats , Cells, Cultured , Cochlea , Cell Biology , Ouabain , Toxicity , Rats, Sprague-Dawley , Spiral Ganglion
16.
Chinese Journal of Oncology ; (12): 484-488, 2011.
Article in Chinese | WPRIM | ID: wpr-320189

ABSTRACT

<p><b>OBJECTIVE</b>Gastric cancer cells are insensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). To sensitize gastric cancer cells to TRAIL, we treated gastric cancer MGC803 cells with TRAIL and cisplatin.</p><p><b>METHODS</b>Cell proliferation was measured using MTT assay. Cell apoptosis was determined by flow cytometry. Expression of proteins was analyzed by Western blot. The distribution of lipid rafts and death receptors was analyzed by immunofluorescence microscopy. MGC803 cells were pretreated with 50 mg/L nystatin for 1 h, and followed by the treatment of cisplatin and TRAIL.</p><p><b>RESULTS</b>100 µg/L TRAIL resulted in (8.51 ± 3.45)% inhibition of cell proliferation and caused (3.26 ± 0.89)% cell apoptosis in MGC803 cells. Compared with the treatment with cisplatin alone, treatment with TRAIL (100 µg/L) and cisplatin (8.49 mg/L, IC(50) dose of 24 h) led to a dramatic increase in both inhibition of cell proliferation [(52.58 ± 4.57)% vs. (76.43 ± 5.35)%, P < 0.05] and cell apoptosis [(23.10 ± 3.41)% vs. (42.56 ± 4.11)%, P < 0.05]. Moreover, cleavage of caspase-8 and caspase-3 was detected. TRAIL (100 µg/L) did not induce obvious lipid rafts aggregation and death receptor 4 (DR4) clustering, while cisplatin (8.49 mg/L) significantly promoted the localization of DR4 in aggregated lipid rafts. Pretreatment with 50 mg/L nystatin, a cholesterol-sequestering agent, triggered (3.66 ± 0.52)% cell apoptosis after 24 h. Pretreatment with nystatin for 1 h before the addition of 8.49 mg/L cisplatin for 24 h caused a decreased tendency to cell apoptosis [(25.74 ± 3.28)% vs. (22.76 ± 2.97)%]. While, pretreatment with nystatin before the addition of cisplatin and TRAIL, the proportion of apoptotic cells decreased from (43.16 ± 4.26)% to (31.52 ± 3.99)% (P < 0.05).</p><p><b>CONCLUSION</b>Cisplatin enhances TRAIL-induced apoptosis in gastric cancer MGC803 cells through clustering death receptors into lipid rafts.</p>


Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Apoptosis , Caspase 3 , Metabolism , Caspase 8 , Metabolism , Cell Line, Tumor , Cell Proliferation , Cisplatin , Pharmacology , Dose-Response Relationship, Drug , Membrane Microdomains , Metabolism , Nystatin , Pharmacology , Receptors, TNF-Related Apoptosis-Inducing Ligand , Metabolism , Stomach Neoplasms , Metabolism , Pathology , TNF-Related Apoptosis-Inducing Ligand , Pharmacology
17.
Chinese Journal of Cancer ; (12): 490-496, 2011.
Article in English | WPRIM | ID: wpr-294497

ABSTRACT

Oxaliplatin-based chemotherapy is used for treating gastric cancer. Autophagy has been extensively implicated in cancer cells; however, its function is not fully understood. Our study aimed to determine if oxaliplatin induce autophagy in gastric cancer MGC803 cells and to assess the effect of autophagy on apoptosis induced by oxaliplatin. MGC803 cells were cultured with oxaliplatin. Cell proliferation was measured using MTT assay, and apoptosis was determined by flow cytometry. Protein expression was detected by Western blot. Autophagy was observed using fluorescent microscopy. Our results showed that the rate of apoptosis was 9.73% and 16.36% when MGC803 cells were treated with 5 and 20 μg/mL oxaliplatin for 24 h, respectively. In addition, caspase activation and poly ADP-ribose polymerase (PARP) cleavage were detected. Furthermore, when MGC803 cells were treated with oxaliplatin for 24 h, an accumulation of punctate LC3 and an increase of LC3-II protein were also detected, indicating the activation of autophagy. Phosphorylation of Akt and mTOR were inhibited by oxaliplatin. Compared to oxaliplatin alone, the combination of autophagy inhibitor chlorochine and oxaliplatin significantly enhanced the inhibition of cell proliferation and the induction of cell apoptosis. In conclusion, oxaliplatin-induced protective autophagy partially prevents apoptosis in gastric cancer MGC803 cells. The combination of autophagy inhibitor and oxaliplatin may be a new therapeutic option for gastric cancer.


Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Apoptosis , Autophagy , Caspase 3 , Metabolism , Caspase 8 , Metabolism , Cell Line, Tumor , Cell Proliferation , Organoplatinum Compounds , Pharmacology , Phosphatidylinositol 3-Kinase , Metabolism , Poly(ADP-ribose) Polymerases , Metabolism , Proto-Oncogene Proteins c-akt , Metabolism , Signal Transduction , Stomach Neoplasms , Metabolism , Pathology , TOR Serine-Threonine Kinases , Metabolism
18.
Journal of Clinical Otorhinolaryngology Head and Neck Surgery ; (24): 293-296, 2010.
Article in Chinese | WPRIM | ID: wpr-748013

ABSTRACT

OBJECTIVE@#To retrospectively analysis the clinical data of facial nerve defects repair with greater auricular nerve graft.@*METHOD@#The transmastoid approach was adopted to repair the facial nerve defects by means of nerve grafting. Preoperative and postoperative facial nerve functions were graded according to the House-Brackmann scale.@*RESULT@#The patterns of temporal bone fracture in the 8 patients were longitudinal, most lesions occurred in the region of the second genu and its surrounding, preoperatively, all patients had Grade VI function. In 3 patients of facial nerve tumors, the tumors involved multiple nerve segments, and histologic results were all schwannomas, preoperatively, 1 case had Grade III function, 2 cases had Grade V function. In 2 patients of iatrogenic trauma of the facial nerve, the primary disease was chronic otitis media with cholesteatoma, the lesions were localized at the mastoid segment and the second genu respectively. In 1 patient of molten steel burn, the lesions was localized at the tympanic segment, preoperative facial nerve function was Grade VI. In addition to 3 cases lost to follow-up, the remaining patients, 4 recovered to a Grade III, 3 to a Grade VI, 2 to a Grade V and 2 remained at Grade VI.@*CONCLUSION@#In present study, the most common cause of facial nerve transection was temporal bone fracture. Facial nerve reconstruction by means of greater auricular nerve grafting was a practical and effective method, the best postoperative recovery of facial nerve function was Grade III.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Cranial Nerves , Transplantation , Ear , Facial Nerve Injuries , General Surgery , Facial Paralysis , General Surgery , Mastoid , General Surgery , Nerve Regeneration , Neurosurgical Procedures , Methods , Retrospective Studies , Temporal Bone , Wounds and Injuries , General Surgery
19.
Chinese Journal of Cancer ; (12): 59-64, 2010.
Article in English | WPRIM | ID: wpr-292639

ABSTRACT

<p><b>BACKGROUND AND OBJECTIVE</b>c-Cbl and Cbl-b are two ubiquitous members of the Casitas B-lineage lymphoma (Cbl) family, which play important roles in the downregulation of epidermal growth factor receptor (EGFR) by acting as E3 ubiquitin ligases and multiadaptor proteins. This study investigated the expression of c-Cbl, Cbl-b, and EGFR in gastric carcinoma and its clinical significance.</p><p><b>METHODS</b>The expressions of c-Cbl, Cbl-b, and EGFR were detected by immunohistochemistry using tissue microarrays consisting of 124 specimens of gastric carcinoma and 16 specimens of normal gastric mucosa. The relationship between the expressions of c-Cbl, Cbl-b, and EGFR and clinicopathologic factors of gastric carcinoma were analyzed statistically.</p><p><b>RESULTS</b>The positive rates of c-Cbl, Cbl-b, and EGFR were higher in the gastric carcinoma group than in the normal group (71.0% vs. 18.0%, P<0.01; 82.3% vs. 25.0%, P<0.01; 56.5% vs. 12.5%, P<0.01, respectively). The expression of c-Cbl was positively correlated with depth of invasion (r=0.219, P=0.015), and TNM staging (r=0.266, P=0.003). The expression of Cbl-b was positively correlated with lymph node metastasis (r=0.190, P<0.034) and TNM staging (r=0.298, P<0.001). The expression of EGFR was positively correlated with depth of invasion (r=0.286, P<0.001) and TNM staging (r=0.362, P=0.000). The expression of both c-Cbl and Cbl-b was positively correlated with EGFR (r=0.241, P=0.007; r=0.183, P=0.042, respectively). Synchronous strong-positive expressions of c-Cbl, Cbl-b, and EGFR were observed in 27 specimens of gastric carcinoma, most of which were at advanced stage.</p><p><b>CONCLUSIONS</b>Overexpressions of c-Cbl, Cbl-b, and EGFR are closely related to the invasion and progression of gastric carcinoma. c-Cbl and Cbl-b may serve as novel molecular markers for gastric carcinoma.</p>


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Adaptor Proteins, Signal Transducing , Metabolism , Adenocarcinoma , Metabolism , Pathology , Biomarkers, Tumor , Metabolism , Disease Progression , Lymphatic Metastasis , Neoplasm Invasiveness , Neoplasm Staging , Proto-Oncogene Proteins c-cbl , Metabolism , ErbB Receptors , Metabolism , Stomach Neoplasms , Metabolism , Pathology
20.
Journal of Experimental Hematology ; (6): 1448-1452, 2009.
Article in Chinese | WPRIM | ID: wpr-328623

ABSTRACT

The objective of study was to investigate the origin and to classify the subtype of N-methyl-N-nitrosourea (MNU)-induced thymic lymphomas in mice. Histopathologic, immunohistochemical and ultrastructural studies were performed to analyze the pathological features of the neoplasms. The results showed that the thymus in all cases became totally replaced by sheets of cells of the lymphoid series. All the tumors coexpressed CD3 and TdT. Transmission electron microscopic study showed the plasma membranes of malignant lymphoma cells were smooth. The nuclear profiles were usually regular, with varying percentage of convoluted nuclei. Few cell organoids were observed in cytoplasm. In conclusion, all the MNU-induced tumor classified by histopathologic, immunohistochemical and ultrastructural studies as precursor lymphoblastic lymphoma that were unquestionably related to the thymus origin and T-cell lineage.


Subject(s)
Animals , Female , Male , Mice , Lymphoma , Pathology , Methylnitrosourea , Mice, Inbred C57BL , Thymus Gland , Pathology , Thymus Neoplasms , Pathology
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