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Objective:To detect gene mutations in 1 patient with Vohwinkel syndrome who presented with palmoplantar keratoderma, pseudo-ainhum and deafness.Methods:Clinical data were collected from the proband, and a genetic test was performed to identify mutation sites.Results:Clinical manifestations of the proband were consistent with classical Vohwinkel syndrome. The genetic test revealed a heterozygous mutation c.160A>C (p.N54H) in the GJB2 gene, which was not detected in her parents or healthy controls.Conclusion:The heterozygous mutation c.160A>C (p.N54H) in the GJB2 gene was first identified in a patient with classical Vohwinkel syndrome, and there were overlaps in mutation sites between classical Vohwinkel syndrome and palmoplantar keratoderma with deafness.
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The detection technology based on micro-nanofluidics has been developed fast with wide applications in biochemical analysis and clinical diagnostics because of its small sample volume requirement, rapid detection and portability. Recently, nanofluidics emerges for DNA sequencing and biomarker detection. With nanopore technology,whole genome sequence in 24 hours with a cost of lower than$1000 could be realized. However, improvement in the detection accuracy and repeatability are still desired for clinic diagnostics. Nanopore technology could be powerful tools for clinical diagnostics, providing new opportunities for laboratory medicine.
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The detection technology based on micro-nanofluidics has been developed fast with wide applications in biochemical analysis and clinical diagnostics because of its small sample volume requirement, rapid detection and portability. Recently, nanofluidics emerges for DNA sequencing and biomarker detection. With nanopore technology,whole genome sequence in 24 hours with a cost of lower than $1000 could be realized. However, improvement in the detection accuracy and repeatability are still desired for clinic diagnostics. Nanopore technology could be powerful tools for clinical diagnostics, providing new opportunities for laboratory medicine.
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Based on the results of previous data mining,the mechanism of high frequency use of Tibetan medicine in the treatment of high altitude polycythemia(HAPC) was analyzed in this study by network pharmacology. The author obtained the high frequency use data on Tibetan medicine Terminalia chebula,Aucklandia lappa,Crocus sativus and Myristica fragrans for the treatment of HAPC by data mining in the previous period. The first five main active ingredients of each high frequency Tibetan medicine were screened out by reviewing comprehensive literature and TCMSP database. The potential targets of each medicine were screened by PharmMapper and Drug Bank database,and then the targets were imported into MAS 3. 0 database to obtain the corresponding path information. The KEGG database was used for path annotation and GO function enrichment analysis. Finally,Cystoscope 3. 4. 0 software was used to construct " compound-target-path" network for four high-frequency Tibetan medicines. Among them,the target points of four herbs related to HAPC were 16(T. chebula),20(A. lappa),20(C. sativus),and 15(M. fragrans). The common target points included BHMT,F2,ADH5,AKR1 C2,GSK3 B,INSR and PDE4 B,involving pathways related to T. chebula(17),A. lappa(17),C. sativus(24) and M. fragrans(14),and the common pathway was metabolism of xenobiotics by cytochrome P450. The results showed that high-frequency Tibetan medicine had common pathways and targets in treating HAPC,such as T. chebula,A. lappa,C. sativus and M. fragrans.The medicines could reduce hemoglobin and enhance immunity by mediating cell proliferation and oxidative stress,exerting anti-inflammatory effects and participating in regulating blood vessels,showing therapeutic effects for HAPC. In this study,the multi-component,multi-target and multi-pathway mechanism of Tibetan medicine in preventing and treating HAPC was analyzed from the information level,providing a useful reference for further study of Tibetan medicine in preventing and treating plateau diseases from the multi-dimensional perspective.
Subject(s)
Humans , Data Mining , Glycogen Synthase Kinase 3 , Medicine, Chinese Traditional , Medicine, Tibetan Traditional , Polycythemia摘要
Xiaochaihu decoction is a classic prescription of traditional Chinese medicine. Modern research has proved its anti-depression effect. However, its pharmacological mechanism for anti-depression effect is difficult to be unveiled because of the complexity of compound Chinese medicines. Bupleuri Radix and Scutellariae Radix is the core drug pair of Xiaochaihu decoction. In this research, Bupleuri Radix and Scutellariae Radix were analyzed by the integrative pharmacology platform to study its molecular mechanism for anti-depression. One hundred and sixteen active ingredients were predicted, 62 for Bupleuri Radix, mainly including saikosaponins, acids, alcohols, and 54 for Scutellariae Radix, mainly including flavonoids and glycosides. Its anti-depression effect was relevant to 118 core targets, including 22 known disease targets, such as serotonin receptor(HTR2C), activating transcription factor(ATF1, ATF2), δ opioid receptor(OPRD1), μ opioid receptor (OPRM1), κ opioid receptor(OPRK1), inositol monophosphatase(IMPA1), Toll-like receptor 4 (TLR4), histamine H1 receptor(HRH1), neurotrophic factor tyrosine kinase receptor1 (NTRK1), Glycogen synthetase kinase 3β(GSK3β), etc. The antidepressant effect involved positive regulation of transcription from RNA polymerase Ⅱ promoter, transcription factor binding, cytosol, transcriptional regulation of DNA template, enzyme binding, endocrine system, nervous system, neurotrophin signaling pathway, cell growth and death, signal transduction, thyroid hormone signaling pathway and other related biological processes and metabolic pathways. This study provides a scientific evidence for further study of the anti-depression mechanism of this drug pair.
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OBJECTIVE@#To investigate the effects of Birinapant on hepatocellular carcinoma cells and its related molecular mechanisms.@*METHODS@#Human hepatocellular carcinoma cells QGY-7701 were treated with 0, 1, 5, 25 and 125 nmol/L Birinapant for 24, 48 and 72 hours respectively, each experiment 3 wells.The proliferation activity of cells, the apoptosis levels, the cells nuclear type, the mitochondrial membrane potential, the transcription and expression levels of genes and the cytotoxicity of Birinapant were analyzed.At the same time, 4-week-old male BALB/C mice were randomly divided into 5 groups, with 20 mice in each group.The mice were inguinal injected with QGY-7701 cells, and then subcutaneous injected with Birinapant (concentrations ranging from 0, 1, 5, 25, 125 μg/kg) in each group after two days, once every other day.On 18 day since first Birinapant injection, 10 mice were killed in each group to weigh tumor tissue and survival time was recorded from the remaining 10 mice.The effects of Birinapant on the growth of the tumor and the survival time of tumor-bearing mice were observed.@*RESULTS@#Compared with the negative control (NC) group, the proliferation activity of QGY-7701 was inhibited significantly after Birinapant treatment and the apoptosis levels were increased significantly (<0.01).The cell mitochondrial membrane potential was decreased and the karyotype was changed (<0.01).At the same time, the transcription and expression levels of genes cellular inhibitor of apoptosis protein 1(cIAP-1), cellular inhibitor of apoptosis protein 2(cIAP-2), ras, raf, mek and erk were significantly decreased (<0.01), while the expression levels of caspase-3 and caspase-9 genes were up-regulated (<0.01).Compared with the model group (MG), the growth of the tumor was inhibited significantly and the survival time of the tumor-bearing mice was prolonged after Birinapant treatment (<0.01).@*CONCLUSIONS@#Birinapant can inhibit the expression of cIAP-1, cIAP-2 and the proteins of Ras-Raf-MEK-ERK signal pathways, so as to activate the mitochondria mediated endogenous apoptosis pathway.Birinapant shows a certain inhibitory effect on liver cancer.
Subject(s)
Animals , Humans , Male , Mice , Apoptosis , Carcinoma, Hepatocellular , Cell Line, Tumor , Dipeptides , Indoles , Liver Neoplasms , Mice, Inbred BALB C , Mitochondrial Proteins摘要
Objective@#To explore the effect of the AXL expression on the chemosensitivity of prostate cancer PC-3 and DU145 cells to docetaxel and possible mechanisms.@*METHODS@#Using Western blot, we examined the expressions of the AXL protein, p-AXL and Gas6 in the docetaxel-resistant PC-3 (PC-3-DR) and DU145 (DU145-DR) cells stimulated with gradually increased concentrations of docetaxel. We transfected the PC-3 and DU145 cells with negative NC ShRNA and AXL-ShRNA, respectively, which were confirmed to be effective, detected the proliferation, apoptosis and cycle distribution of the cells by CCK8, MTT and flow cytometry after treated with the AXL-inhibitor MP470 and/or docetaxel, and determined the expression of the ABCB1 protein in the PC-3-DR and DU145-DR cells after intervention with the AXL-inhibitor R428 and/or docetaxel.@*RESULTS@#The expression of the AXL protein in the PC-3 and DU145 cells was significantly increased after docetaxel treatment (P <0.05). The expressions AXL and p-AXL were remarkably higher (P <0.05) while that of Gas6 markedly lower (P <0.05) in the PC-3 and DU145 than in the PC-3-DR and DU145-DR cells. The inhibitory effect of docetaxel on the proliferation and its enhancing effect on the apoptosis of the PC-3 and DU145 cells were significantly decreased at 48 hours after AXL transfection (P <0.05). MP470 obviously suppressed the growth and promoted the apoptosis of the PC-3-DR and DU145-DR cells, with a higher percentage of the cells in the G2/M phase when combined with docetaxel than used alone (P <0.05). R428 markedly reduced the expression of ABCB1 in the PC-3-DR and DU145-DR cells, even more significantly in combination with docetaxel than used alone (P <0.05).@*CONCLUSIONS@#The elevated expression of AXL enhances the docetaxel-resistance of PC-3 and DU145 prostate cancer cells and AXL intervention improves their chemosensitivity to docetaxel, which may be associated with the increased cell apoptosis in the G2/M phase and decreased expression of ABCB1.
Subject(s)
Humans , Male , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Metabolism , Antineoplastic Agents , Pharmacology , Apoptosis , Cell Count , Cell Cycle , Cell Line, Tumor , Cell Proliferation , Docetaxel , Drug Resistance, Neoplasm , Intercellular Signaling Peptides and Proteins , Metabolism , Prostatic Neoplasms , Drug Therapy , Metabolism , Pathology , Proto-Oncogene Proteins , Genetics , Metabolism , Pyrimidines , Pharmacology , RNA, Small Interfering , Receptor Protein-Tyrosine Kinases , Genetics , Metabolism , Taxoids , Pharmacology摘要
This study using traditional Chinese medicine inheritance support software(TCMISS) to analyze the prescription rules of Tibetan medicine containing Terminalia chebula in the Encyclopedia of Chinese Medicine-Tibetan Medicine, Tibetan Medicine Composition Preparation of Modern Research and Clinical Application and Common Interpretation of Tibetan Medicine and so on. TCMISS(V2.5) was used to build a prescription database of Tibetan medicine containing T. chebula.The software statistical statement module, association rules and improved mutual information method and other data mining technologies were adopted to analyze the common herbs, combination rules and core combination of prescriptions containing T. chebula.Total 502 prescriptions containing T. chebula were analyzed and 14 common herbal combinations were summarized, whose ingredients mostly had the functions of clearing heat and detoxicating, promoting blood circulation and stopping pain, warming the middle-jiao and promoting the circulation of Qi. Prescriptions containing T. chebula were commonly used to treat 640 kinds of diseases, there are 22 kinds with high frequency(≥12) in which the representative "Tripa" disease, antiquated febrile symptoms, food poisoning had the highest frequency.T. chebula had different therapeutic effects through different compatibility.The complex composing and medication regularities of Tibetan medicine containing T. chebula have been clarified by TCMISS. That will provide reference for the clinical application of T. chebula and the new development.
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Tibetan medicine "Dida" isoccasionally misused due to its complex origins, which ultimately affects its clinical efficacy. The accurate name, origin, property, and efficacy of "Dida"are highly important for its further research and development. In the present study, by viewing the classic Tibetan medicine and modern literature, and combining the clinical practice of Tibetan medicine, the origins, properties and the clinic effects of "Dida" were defined. "Dida" originated from multiple plant species of Swertia, Gentianopsis, Halenia, Lomatogonium, Comastoma(Gentianaceae), Hedyotis (Saxifragaceae) and Erysimum (Cruciferae). The medicinal properties of "Dida" is mainly bitter and cold. It has been commonly used to treat febrile diseases and hepatic and gall diseases. This study suggested that the relevant herbalogical study, species identification and pharmacological effects of "Dida" should be taken based on the Tibetan medicine theories and clinical practice. Thus the medicine can be better used and ensure its safety and quality simultaneously.
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Objective To study the serum levels of melatonin,tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) in multiple sclerosis (MS) patients and the correlation with disability.Methods Forty patients with multiple sclerosis were collected as MS group and 30 healthy participants were collected as control group.Serum levels of melatonin and cytokines,including IFN-γ and TNF-,were detected in all participants by the enzyme-linked immunosorbent assay (ELISA) method;disability status of patients with MS was evaluated by EDSS scale.The relevant analysis between serum melatonin,TNF-α,IFN-γ levels and EDSS score in patients with MS was conducted.Results The concentration of serum melatonin in MS group was significantly lower than control group (P<0.01).TNF-α levels were higher than control group (P<0.05) and the difference was statistically significant between MS patients and control group.Among MS group and control group,no significant correlation with the serum levels of IFN-γ was seen.The serum melatonin level was inversely correlated with EDSS score in MS patients (r =-0.76,P<0.01),and positively correlated with TNF-α (r =0.83,P<0.01) and as compared to IFN-γ,no significant correlation was found (r =0.17,P>0.05).Conclusion The decrease of melatonin and increase of TNF-α can be a factor in the inflammatory reaction in patients with MS,and is closely related with dysfunction occurring in multiple sclerosis.Serum melatonin and TNF-α can be used as laboratory indicators to monitor clinical curative effect and evaluate prognosis of MS.
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Objective To investigate the clinical features and pathogenic genes of a familial hypokalemic periodic paralysis ( HOKPP).Methods PCR amplification and DNA sequencing were used to screen candidate genes of the HOKPP family members (CACNA1S, SCN4A, KCNE3), and the clinical features were carefully analyzed at the same time.Results The sequencing analyses of the SCN4A gene in the proband identified three nucleotide sequence mutations, which influenced the amino acid sequence of the skeletal sodium channel.One of the mutations was identified as a C/T heterozygous pattern at the 2111th nucleotide position in exon 13, resulting in a change from Thr to Met at the 704th amino acid position of the sodium channel protein.All affected patients carried the Thr704Met mutation, whereas unaffected family members did not.Clinical symptoms in this family followed an autosomal dominant inheritance pattern.Muscles weakness, pain and hypokalemia in the period between attacks were seen in all patients.Paralytic symptoms occurred early, lasted longer and recurred frequently, while cold was the main predisposing factor.With the progress of the disease, patients represented persistent weakness and atrophy in proximal muscles.Conclusions Mutation (Thr704Met) in the SCN4A gene should be responsible for this family.This mutation causes severe HOKPP and progressive muscle atrophy.
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<p><b>OBJECTIVE</b>To investigate the prevalence of respiratory syncytial virus (RSV) infection in hospitalized children and the relationship between the prevalence and the climate change in Suzhou, China.</p><p><b>METHODS</b>A total of 42 664 nasopharyngeal secretions from hospitalized children with acute respiratory infection at the Suzhou Children's Hospital were screened for RSV antigens using direct immunofluorescence. Monthly meteorological data (mean monthly air temperature, monthly relative humidity, monthly rainfall, total monthly sunshine duration, and mean monthly wind velocity) in Suzhou between 2001 and 2011 were collected. The correlations between RSV detection rate and climatic factors were evaluated using correlation and stepwise regression analysis.</p><p><b>RESULTS</b>The annual RSV infection rate in hospitalized children with respiratory infection in the Suzhou Children's Hospital varied between 11.85% and 27.30% from 2001 to 2011. In the 9 epidemic seasons, each spanning from November to April of the next year, from 2001 to 2010, the RSV detection rates were 40.75%, 22.72%, 39.93%, 27.37%, 42.71%, 21.28%, 38.57%, 19.86%, and 29.73%, respectively; there were significant differences in the detection rate between the epidemic seasons. The monthly RSV detection rate was negatively correlated with mean monthly air temperature, total monthly sunshine duration, monthly rainfall, monthly relative humidity, and mean monthly wind velocity (P<0.05). Stepwise regression analysis showed that mean monthly air temperature fitted into a linear model (R(2)=0.64, P<0.01).</p><p><b>CONCLUSIONS</b>From 2001 to 2011, RSV infection in Suzhou was predominantly prevalent between November and April of the next year. As a whole, the infection rate of RSV reached a peak every other year. Air temperature played an important role in the epidemics of RSV infection in Suzhou.</p>
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Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Child, Hospitalized , China , Epidemiology , Climate Change , Prevalence , Respiratory Syncytial Virus Infections , Epidemiology摘要
<p><b>OBJECTIVE</b>To investigate the effect of the Uremic Clearance Granule (UCG, ), a Chinese patent medicine, on tubular epithelial-to-mesenchymal transition (EMT) in a unilateral ureteral obstruction (UUO) model in vivo and transforming growth factor (TGF)-β1 induced EMT of HK-2 cells in vitro.</p><p><b>METHODS</b>In vivo study, 50 Sprague Dawley rats were divided into three groups: a sham operation group (n=10), a UUO group (n=20), and a UUO with UCG treatment group (n=20). The UCG was given at a dose of 4.5 g/kg body weight per day by gavage after surgery. In vitro study, HK-2 cells were cultured in 10% fetal bovine serum (FBS), 10% healthy rat serum, 10% FBS and TGF-β1 (10 ng/mL), 10% healthy rat serum and TGF-β1, or 10% rat serum containing the uremic clearance granule and TGF-β1. The expression of the epithelial marker E-cadherin and the mesenchymal markers vimentin and α-smooth muscle actin (α-SMA) in kidney tissues and HK-2 cells were investigated by Western blot analysis and immunofluorescence staining.</p><p><b>RESULTS</b>The rats of the UUO group showed obvious tubulointerstitial fibrosis, compared with the sham operation group rats. Tubulointerstitial fibrosis score was reduced by 17.5%±1.1% at day 7 and by 20.0%±1.2% at day 14 in the UCG-treated group, compared with the UUO group. The UCG could maintained expression of E-cadherin and suppressed expression of vimentin and α-SMA in kidney tissues of UUO rats at days 7 and 14, as determined by Western blot analysis and immunofluorescence staining. Rat serum containing the UCG partially inhibited TGF-β1-induced fibroblast phenotype of HK-2 cells and maintained the epithelial morphology of HK-2 cells in vitro. This occurred partially through a reduction of vimentin expression and an increase of E-cadherin expression.</p><p><b>CONCLUSION</b>These results suggest that the UCG prevents tubular EMT and may be a promising agent for treating tubulointerstitial fibrosis.</p>
Subject(s)
Animals , Male , Rats , Blood , Blotting, Western , Cell Line , Culture Media , Epithelial-Mesenchymal Transition , Fluorescent Antibody Technique , In Vitro Techniques , Kidney Tubules , Pathology , Rats, Sprague-Dawley , Uremia , Pathology摘要
Background Pupillary light reflex has been widely used in the diagnosis and evaluation of visual system and nervous system diseases.However,in animal experiments,functional evaluation of the visual system and nervous system needs more advanced technology and are affected by many factors.Objective This study was to explore the use of the dynamic pupillometer in evaluating pupillary light reflex and to discuss the influence of brightness of stimulate on relevant curve parameters in C57BL/6 mouse.Methods Ten healthy SPF male C57BL/6 mice were collected in this experiment.White light of five luminance levels (2,8,32,128,256 cd/m2) was used to stimulate the mice following a 2-hour dark adaptation.The stimulation was given at the 60-second intervals,for a duration of 100 ms at every stimulation.An infrared camera and video capture card were used to capture digital images during the measuring process in a scotopic environment,at a speed of 60 frames per second.Measuring outcome was saved in the*.AVI format.A software that was developed by our group was used to determine pupil diameter and output pupillary light reflex curve offline.Pupil initial diameter (R1),constriction amplitude (CA),constriction velocity (CV),latency (T1),time for maximum velocity (T2),time for maximum constriction (T3),time for maximun con-striction to 10.1% R1 re-dilation (RT)and re-dilation velocity (RV)were assessed,and the correlations between luminosity and measuring parameters were analyzed using the Spearman rank correlation.The use of animals followed the Regulations for thd Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.Results R1 values showed no statistically significant difference among the 5 different luminosity groups(F=1.117,P=0.361).A positive linear correlation was found between stimulating luminosity and CA(r=0.508,P< 0.01),but negative correlations were seen between stimulating luminosity and CV or RV (r=-0.625,-0.609,P<0.01).T1 and T2 values in the 5 different luminosity groups were not statistically significant (F =0.202,P =0.936 ; F =1.584,P =0.195).The different levels of stimulating luminosity showed positive linear correlations with T3 and RT values (r =0.791,0.609,P< 0.01).Conclusions The dynamic pupillometer can quantitatively measure the pupillary light reflex of C57BL/6 mice.The pupillary light reflex dynamic curve parameters of mouse were affected by stimulus luminosity levels.These outcomes offer a basis for the application of the dynamic pupillometer system for measuring pupillary light reflex in animal models.
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<p><b>OBJECTIVE</b>To observe the renal protection effects of Compound Shenhua Tablet (CST) on diabetic nephropathy (DN) rats.</p><p><b>METHODS</b>DN rats were given a normal diet for 9 months after they were induced by intraperitoneal injection of STZ at the dose of 65 mg/kg after uninephrectomized. They were randomly divided into 4 groups, i. e., the normal control group, the model control group, the CST group, and the Irbesartan group. The intervention was given by gastrogavage for 6 weeks. The general state, 24 h urine protein, urine micro-albumin (mAlb), serum creatinine (SCr), blood urea nitrogen (BUN), glucose (GLU), triglyceride (TG), total cholesterol (TC), total protein (TP), and albumin (ALB) levels were observed before and after intervention. Renal pathological changes were observed by PAS staining and transmission electron microscope.</p><p><b>RESULTS</b>After 6 weeks of drug intervention, when compared with the model control group, the general state was improved in the CST group and the Irbesartan group. The levels of 24 h urine protein, urine mAlb, SCr, BUN, GLU, TG, and TC were obviously lower in the CST group and the Irbesartan group than in the model group as well as in the same group before treatment (P<0.05, P<0.01). There was no statistical difference between the two treatment groups (P>0.05). The renal pathological changes and the renal ultrastructure were improved to some degree in the two groups when compared with those in the model control group.</p><p><b>CONCLUSIONS</b>CST could attenuate the renal damage of diabetes and delay renal deterioration process. Its effectiveness was equivalent to that of Irbesartan.</p>
Subject(s)
Animals , Male , Rats , Diabetes Mellitus, Experimental , Drug Therapy , Diabetic Nephropathies , Drug Therapy , Drugs, Chinese Herbal , Pharmacology , Kidney , Phytotherapy , Rats, Sprague-Dawley摘要
<p><b>BACKGROUND</b>Cisplatin (DDP) is one of most effective and most commonly used therapeutic agent in treating tumors, it can accumulate in the kidney and lead to acute renal failure. MicroRNA-181a can induce cell apoptosis by suppressing the expression of Bcl-2 family. In the present study, we investigated the role of microRNA-181a in the apoptosis of tubular epithelial cell induced by DDP.</p><p><b>METHODS</b>HK-2 cells were cultured, transfected with microRNA-181a inhibitor for 48 hours, and stimulated with 50 µmol/L cisplatin for 24 hours. MicroRNA-181a expression was analyzed by real time PCR, and cell apoptosis was detected by flow cytometry. Moreover, Bcl-2 and Bcl-2-associated X protein (Bax) expression were measured by Western blotting.</p><p><b>RESULTS</b>MicroRNA-181a expression significantly down-regulated in cells transfected with microRNA-181a inhibitor, compared with that in untransfectd cells (21.19 ± 2.01 vs. 38.87 ± 1.97, P < 0.05). Cell apoptosis induced by DDP significantly decreased in cells transfected with MicroRNA-181a inhibitor. Compared with DDP treated cells alone, Bcl-2 expression strikingly was up-regulated and Bax expression was down-regulated in cells transfected with microRNA-181a inhibitor.</p><p><b>CONCLUSION</b>One pathway of DDP induces apoptosis of tubular epithelial cell by suppressing Bcl-2 expression is achieved by regulating the target gene of MicroRNA-181a.</p>
Subject(s)
Humans , Apoptosis , Genetics , Blotting, Western , Cell Line , Cisplatin , Pharmacology , Flow Cytometry , MicroRNAs , Genetics , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Metabolism , RNA, Small Interfering , Genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Transfection , bcl-2-Associated X Protein , Metabolism摘要
Background Light-induced retinal damage models vary as many influence factors,herein the modeling method is difficult to copy.It is necessary to establish the grading standardization of retinal damage after retinal light exposure.Objective This study was to improve the modeling method and establish a grading standardization for light-induced retinal damage in rat.Methods Twenty-four SPF 8-10 week-old male SD rats were randomly divided into 4 groups and 6 eyes for each group.The rats were exposed to light intense of 5000 lx for 1,2,3 hours respectively in 3 groups,and other 6 rats served as the normal group.Full-field light exposure experiment was performed for each individual rat separately,and an annular illumination box was used tO ensure the experimental rat moving in a single direction and exposing the right eye in 5000 lx light surrounding during experimental duration.Ganzfeid electroretinogram(ERG)was recorded from the experimental rats at the fifth day after light exposure,and the animals were then sacrificed for histopathology observation to evaluate the retinal thickness change.All procedures which involved animals adhered to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.Results After exposing to intensity light for 1,2,3 hours,the b-wave amplitudes of rod response,maximal mixed response,oscillatory potential in scotopic ERG as well as cone response,20 Hz flicker response of photopic ERG were significant declined as lapse of light exposure time(F=71.690,P=0.000;F=56.250,P=0.000;F=23.610,P=0.000:F=27.130,P=0.000;F=27.030,P=0.000)and lowed by 26.2%,52.5%,70.7%,24.4%,39.3%,58.1%respectively at the end of experiment.Meanwhile,the b-wave latencies of rod response,maximal mixed response in scotopic ERG as well as cone response of photopic ERG were evidently different among different groups (F=1.370,P=0.282;F:0.800,P=0.508;F=11.840,P=0.000;F=2.080,P=0.136).Light induced retinal damage located mainly at the temporal retina area.After intensity light exposure for 1,2,3 hours,the thickness of outer nuclear layer at the superior temporal retina attenuated by 11.3%,25.6%and 72.5%,respectively(P<0.05).A significant difference was seen in mean thickness of outer nuclear layer at superior temporal retina among different groups(F=410.27,P=0.000). Conclusion A standardized grading method for light-induced retinal damage is recommended.The continuous illumination in a intensity of 5000 Ix for 1,2,3 hours can induce the mild,moderate or severe retinal damage respectively at temporal retina.
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Objective To investigate the expression of kai1 and nm23 mRNA in esophageal carcinoma, and to explore the clinicopathological significance of kail and nm23 mRNA in the progression of esophageal carcinoma. Methods To detect mRNA expression of kai1 and nm23 in 46 cases of esophageal carcinoma and 34 cases normal esophageal tissues closely adjacent to carcinoma by in situ hybridization.Results The incidence of kai1 (91.3 %>64.7 %, χ2 =8.65, P =0.003) and nm23 (43.5 %>5.9 %, χ2=13.86,P <0.001) in esophageal carcinoma was significantly higher than in normal esophageal tissues . The expression of nm23 was correlated with the pathological stages (r =-0.379, P =0.009) and lymph node metastasis (χ2 =6.47, P =0.011). The expression of mRNA had positive correlation between kai1and nm23 in esophageal carcinoma (r =0.298, P =0.007). Conclusion The expression of nm23 may play an important role in the occurrence, development and clinicopathological features of esophageal carcinoma. Combined detection of kai1 and nm23 may be helpful in further directing the clinical therapy of esophageal carcinoma.
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<p><b>OBJECTIVE</b>To investigate the effect of PI-3K and p38MAPK signal pathways on the cyclooxygenase-2 (COX-2) expression induced by the epidermal growth factor (EGF) in PC-3 cells.</p><p><b>METHODS</b>PC-3 cell proliferation was detected by methylthiazolyl tetrazolium (MTT) assay after stimulated by EGF (0 microg/L), EGF (10 microg/L), EGF (10 microg/L) + LY294002 (20 micromol/L) and EGF (10 microg/L) + SC203580 (20 micromol/L), and so was the COX-2 expression in the PC-3 cells by RT-PCR and Western blot assay after stimulated the same way for 24 hours. ELISA was used to determine the changes of PGE2 in the culture medium.</p><p><b>RESULTS</b>LY294002 and SC203580 signficantly inhibited PC-3 cell proliferation (P < 0.05), COX-2 expression and PGE2 production after EGF stimulation (P < 0.05).</p><p><b>CONCLUSION</b>EGF can stimulate PC-3 cells into proliferation and induce COX-2 mRNA and the upregulation of its protein expression, while LY294002 and SC203580 can inhibit EGF from the above effects on PC-3 cells.</p>
Subject(s)
Humans , Male , Blotting, Western , Cell Line, Tumor , Cell Proliferation , Cyclooxygenase 2 , Genetics , Metabolism , Dinoprostone , Metabolism , Enzyme-Linked Immunosorbent Assay , Epidermal Growth Factor , Pharmacology , Gene Expression , Phosphatidylinositol 3-Kinases , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction , p38 Mitogen-Activated Protein Kinases , Metabolism摘要
<p><b>OBJECTIVE</b>To evaluate the early operative treatment and clinical results of pelvic fractures associated with urethra disruption.</p><p><b>METHODS</b>From January 1995 to January 2005, 25 patients suffered from pelvic fractures combined urethra disruption treated by operation were retrospectively analyzed. According to Tile's classification, 1 case was stable pelvic fracture, 17 rotational unstable fractures, and 7 rotational combined vertical unstable fractures. The complete urethra rupture were in 23 cases and incomplete in 2 cases. The operative methods included: (1) emergency open reduction and internal fixation of the pelvis combined primary urethra suturing in 2 cases, partial suturing after realignment in 4 cases, realignment in 2 cases, and urethrovaginal penetrating wound repairing in 1 case; (2) primary urethra realignment only and delayed (range, 7 to 21 days) pelvic internal fixation in 10 cases; (3) early cystostomy and delayed (range, 3 to 21 days) urethra realignment and pelvic internal fixation in 6 cases.</p><p><b>RESULTS</b>The mean follow-up time of all patients was 34 months (range from 6 to 120 months). According to Majeed's evaluation, 17 cases of pelvic injury showed excellent results, 5 good, and 3 fare. After urinary catheter removed, the mean maximal urine flow rate of 19 (76%) patients was 18.6 ml/s and the mean scar length between both disrupted ends on the film of excretion urethrography was 0.51 cm. Five (20%) cases suffered in dysuria needed urethral dilatation or further surgery. One (4%) female could not control urination who need a second-look operation. The primary suprapubic soft tissue avulsion wound infection secondary to retropubic abscess was found in 1 case, posterior urethra-stenosis in 5 cases, sexual impotence in 3 cases, and incontinence in 1 case.</p><p><b>CONCLUSIONS</b>The satisfactory reduction and effective fixation of the pelvic fractures is an anatomical basis for receiving "tension-free urethral anastomosis".</p>