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Objective To investigate the mechanism of HSP90 inhibitor AUY-922 reversing the resistance of human neuroblastoma cells to the second generation ALK inhibitor TAE684. Methods The effect of AUY-922 on the proliferation of human neuroblastoma cells SH-SY5Y and KELLY carrying ALK F1174L gene was detected by MTT method. The effect of AUY-922 on cell cycle of SH-SY5Y and KELLY cells was detected by flow cytometry. The effects of AUY-922 on cyclin Cdc2, ALK protein and downstream signal pathways p-Akt, p-Erk, p-stat3 in SH-SY5Y and KELLY cells were detected by Western blot. Results AUY-922 could significantly inhibit the proliferation of SH-SY5Y and KELLY cells, and the IC50 were about 0.30 μmol/L and 0.12 μmol/L, respectively. AUY-922 could induce cell cycle arrest of SH-SY5Y and KELLY cells in G2/M phase in a dose-dependent manner. AUY-922 could degrade Cdc2 and ALK proteins in SH-SY5Y and KELLY cells in a dose-dependent manner, and reduce the levels of p-Akt, p-Erk and p-stat3. Conclusion The reversal effect of HSP90 inhibitor AUY-922 on drug resistance of human neuroblastoma to ALK inhibitor may be related to its induction of G2/M cell cycle arrest, the degradation of ALK protein and the inhibition of downstream signal pathway.
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ObjectiveTo understand the incidence and change trend of thyroid cancer in Qingpu District， Shanghai from 2007 to 2016， and to provide a reference for formulating relevant prevention and treatment strategies. MethodsThe incidence data of thyroid cancer among residents in Qingpu District from 2007 to 2016 were collected using the Shanghai Malignant Tumor Registration System， and the crude incidence rate was calculated for different gender and age groups. The age-standardized incidence rate was calculated using the world standard population， and the annual percentage change （APC） was calculated using Joinpoint software to analyze the time trend of the incidence of thyroid cancer. ResultsThe incidence of thyroid cancer changed from 8.97/105 in 2007 to 52.02/105 in 2016， with an increase of 479.93% （APC=23.60， P<0.05）. The standardized incidence rate of thyroid cancer in men and women was 11.21/105 and 32.11/105， respectively， Male to female incidence ratio was 1∶3. Thyroid cancer in Qingpu District was mainly concentrated in the 25‒64 age group， accounting for 88.03% of the total incidence. ConclusionFrom 2007 to 2016， the incidence of thyroid cancer in Qingpu District， Shanghai has a significant upward trend. The age of high incidence tends to be younger and the incidence of women is significantly higher than that of men. Corresponding prevention and treatment measures should be formulated in consideration of the discovered incidence characteristics.
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Objective@#To analyze the alterations and clinical significance of serum calcium binding protein S100A8/A9 and soluble receptor for advanced glycation end products (sRAGE) levels in patients with chronic obstructive pulmonary disease(COPD).@*Methods@#Enzyme-linked immonosorbent assay was established to detect serum levels of S100A8/A9 and sRAGE in 203 patients with COPD[male166, female 37, aged 52-92 years, average years(69.72±9.079)] and in 41 smoking elderly non-COPD patients[male 35,female 6, aged 55-89 years, average years(68.66±8.74)], and 167 non-smoking healthy subjects as the control group[male 132, female 35, aged 57-92 years, average years(69.13±7.21)] from April 2018 to January 2019. The relationship between the S100A8/A9, sRAGE and clinical biomarkers [the percentage of fored expiratory volume in one second(FEV1) in the predicted value, FEV1/fored vital capacity(FVC), neutrophile granulocyte(NEU)%, pack-year] were investigated. The diagnostic value of S100A8/A9, sRAGE and their combined detection for COPD was analyzed using the subject operating characteristic curve.@*Results@#The serum S100A8/A9 level [(2.70±1.11)μg/ml] in COPD patients was significantly higher than that in the smoking control group [(1.65±0.63) μg/ml] and the non-smoking control group[(0.99±0.48)μg/ml], t=5.807, P<0.000 1; t=18.45, P<0.000 1. The serum S100A8/A9 levels in patients with COPD[GOLD Ⅰ(2.08±1.08) μg/ml, GOLDⅡ (2.58±1.06) μg/ml, GOLD Ⅲ (2.69±1.12) μg/ml, GOLDⅣ (2.95±1.10)μg/ml] were significantly higher than the non-smoking control group(0.99±0.48)μg/ml, t=6.616, P<0.000 1; t=14.56, P<0.000 1; t=17.10, P<0.000 1; t=18.09, P<0.000 1.The serum sRAGE level [(0.29±0.25)ng/ml] in COPD patients was significantly higher than that in the smoking control group[(0.60±0.24)ng/ml] and the non-smoking control group[(0.85±0.35)ng/ml], t=7.367, P<0.000 1; t=18.14, P<0.000 1. The serum sRAGE levels in patients with COPD[GOLD Ⅰ(0.46±0.40),GOLDⅡ (0.28±0.25),GOLD Ⅲ (0.29±0.25),GOLD Ⅳ (0.25±0.19)ng/ml] were significantly lower compared with non-smoking control group[(0.85±0.35)ng/ml], t=3.459, P=0.000 5; t=10.23, P<0.000 1; t=13.95, P<0.000 1; t=11.70, P<0.000 1. Serum S100A8/A9 levels were positively correlated with smoking amount and NEU% (r=0.458 5, P<0.000 1; r=0.228 3, P=0.001 1), negatively correlated with FEV1/FVC, the percentage of FEV1 in the predicted value, and sRAGE(r=-0.190 6, P=0.006 4; r=-0.186 3, P=0.007 8; r=-0.201 7, P=0.003 9). sRAGE levels were negatively correlated with NEU% (r=-0.155 9, P=0.026 4). In the ROC curve, the area under the curve of S100A8/A9, sRAGE and combined detection were 0.922[95%CI(0.897-0.947)], 0.926[95%CI(0.899-0.952)]and 0.966 [95%CI(0.950-0.983)], respectively.@*Conclusion@#S100A8/A9 and sRAGE are closely correlated with the degree of airflow constrains and the levels of serum inflammatory mediators, which are expected to be as potential biomarkers of COPD.
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Objective:To analyze the alterations and clinical significance of serum calcium binding protein S100A8/A9 and soluble receptor for advanced glycation end products (sRAGE) levels in patients with chronic obstructive pulmonary disease(COPD).Methods:Enzyme-linked immonosorbent assay was established to detect serum levels of S100A8/A9 and sRAGE in 203 patients with COPD[male166, female 37, aged 52-92 years, average years(69.72±9.079)] and in 41 smoking elderly non-COPD patients[male 35,female 6, aged 55-89 years, average years(68.66±8.74)], and 167 non-smoking healthy subjects as the control group[male 132, female 35, aged 57-92 years, average years(69.13±7.21)] from April 2018 to January 2019. The relationship between the S100A8/A9, sRAGE and clinical biomarkers [the percentage of fored expiratory volume in one second(FEV 1) in the predicted value, FEV 1/fored vital capacity(FVC), neutrophile granulocyte(NEU)%, pack-year] were investigated. The diagnostic value of S100A8/A9, sRAGE and their combined detection for COPD was analyzed using the subject operating characteristic curve. Results:The serum S100A8/A9 level [(2.70±1.11)μg/ml] in COPD patients was significantly higher than that in the smoking control group [(1.65±0.63) μg/ml] and the non-smoking control group[(0.99±0.48)μg/ml], t=5.807, P<0.000 1; t=18.45, P<0.000 1. The serum S100A8/A9 levels in patients with COPD[GOLD Ⅰ(2.08±1.08) μg/ml, GOLDⅡ (2.58±1.06) μg/ml, GOLD Ⅲ (2.69±1.12) μg/ml, GOLDⅣ (2.95±1.10)μg/ml] were significantly higher than the non-smoking control group(0.99±0.48)μg/ml, t=6.616, P<0.000 1; t=14.56, P<0.000 1; t=17.10, P<0.000 1; t=18.09, P<0.000 1.The serum sRAGE level [(0.29±0.25)ng/ml] in COPD patients was significantly higher than that in the smoking control group[(0.60±0.24)ng/ml] and the non-smoking control group[(0.85±0.35)ng/ml], t=7.367, P<0.000 1; t=18.14, P<0.000 1. The serum sRAGE levels in patients with COPD[GOLD Ⅰ(0.46±0.40),GOLDⅡ (0.28±0.25),GOLD Ⅲ (0.29±0.25),GOLD Ⅳ (0.25±0.19)ng/ml] were significantly lower compared with non-smoking control group[(0.85±0.35)ng/ml], t=3.459, P=0.000 5; t=10.23, P<0.000 1; t=13.95, P<0.000 1; t=11.70, P<0.000 1. Serum S100A8/A9 levels were positively correlated with smoking amount and NEU% ( r=0.458 5, P<0.000 1; r=0.228 3, P=0.001 1), negatively correlated with FEV 1/FVC, the percentage of FEV 1 in the predicted value, and sRAGE( r=-0.190 6, P=0.006 4; r=-0.186 3, P=0.007 8; r=-0.201 7, P=0.003 9). sRAGE levels were negatively correlated with NEU% ( r=-0.155 9, P=0.026 4). In the ROC curve, the area under the curve of S100A8/A9, sRAGE and combined detection were 0.922[95 %CI(0.897-0.947)], 0.926[95 %CI(0.899-0.952)]and 0.966 [95 %CI(0.950-0.983)], respectively. Conclusion:S100A8/A9 and sRAGE are closely correlated with the degree of airflow constrains and the levels of serum inflammatory mediators, which are expected to be as potential biomarkers of COPD.
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Non-small-cell lung cancer (NSCLC), the most common type of lung cancer accounting for 85% of the cases, is often diagnosed at advanced stages owing to the lack of efficient early diagnostic tools. 5-Hydroxymethylcytosine (5hmC) signatures in circulating cell-free DNA (cfDNA) that carries the cancer-specific epigenetic patterns may represent the valuable biomarkers for discriminating tumor and healthy individuals, and thus could be potentially useful for NSCLC diagnosis. Here, we employed a sensitive and reliable method to map genome-wide 5hmC in the cfDNA of Chinese NSCLC patients and detected a significant 5hmC gain in both the gene bodies and promoter regions in the blood samples from tumor patients compared with healthy controls. Specifically, we identified six potential biomarkers from 66 patients and 67 healthy controls (mean decrease accuracy >3.2, P < 3.68E-19) using machine-learning-based tumor classifiers with high accuracy. Thus, the unique signature of 5hmC in tumor patient's cfDNA identified in our study may provide valuable information in facilitating the development of new diagnostic and therapeutic modalities for NSCLC.
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Female , Humans , Male , Middle Aged , 5-Methylcytosine , Blood , Biomarkers, Tumor , Blood , Genetics , Carcinoma, Non-Small-Cell Lung , Blood , Diagnosis , Genetics , Case-Control Studies , Circulating Tumor DNA , Blood , DNA Methylation , Epigenomics , Lung Neoplasms , Blood , Diagnosis , GeneticsABSTRACT
Aim To investigate the anti-tumor effects of FS-108 an Hsp90 inhibitor, on oncogene addicted EBC-1 and A375 cells. Methods SRB assay was performed to investigate cell proliferation. Immunoblot was conducted to investigate the specific proteins. FACS was conducted to test cell cycle distribution and apoptosis. Transwell assay was conducted to investigate cell motility. Results FS-108 significantly suppressed cell proliferation of EBC-1 and A375 cancer cells with IC50 at 25. 53 nmol · L-1 and 30. 02 nmol · L-1 re-spectively. FS-108 treatment triggered the degradation of key client proteins such as c-Met and B-Raf and thereby reduced their downstream AKT and ERK signa-ling pathways. The FACS analysis results demonstrated that FS-108 treatment induced G2/M phase arrest and apoptosis significantly. Furthermore, FS-108 inhibited the migration of EBC-1 and A375 cells. Conclusion As a potent Hsp90 inhibitor, FS-108 can inhibit onco-gene addicted cancer cells proliferation through induc-tion of G2/M phase arrest and apoptosis.
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Objective:To explore the relation of mobile phone addiction to perceived social support and sub-jective well-being in college students. Methods:Totally 4000 college students were selected from 2 colleges,and they were assessed with the Mobile Phone Addiction Inventory (MPAI),Perceived Social Support Scale (PSSS) and subjective well-being scale (SWB). Results:The college students of mobile phone addiction were 1420 cases, accounting for 37. 9%. Except the dimension of negative emotion,the PSSS total scores and its factor scores,the SWB total scores and its factor scores were lower in the Mobile Phone Addiction (MPA)group than in the non-MPA group (Ps<0. 00 1 ). Regression analysis indicated significant negatively predictability of MPAI to subjective well-being and PSSS had significant positively predictability to SWB. The test of mediating effect found that PSSS and its 3 dimensions played a partly mediating role between MPAI and SWB,and the mediation effect account for the total effect 24. 89%,16. 1 1%,17. 33%,17. 78% respectively. Conclusion:There may be a close relation of mobile phone addiction to perceived social support and subjective well-being. Mobile phone addiction could directly affect subjective well-being and indirectly affect subjective well-being through perceived social support.
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BACKGROUND: High-strength titanium alloy can be prepared bY using powder metallurgy technique, but there are still some problems such as containing toxic elements or high elastic modulus in prepared alloys.OBJECTIVE: A new Ti-Mg alloy with non-toxic and elastic modulus which is close to human bones and strengths satisfy the requirements for human body implants was successfully prepared by means of powder metallurgy technology, and the effects of magnesium content on the microstructure and mechanical properties of Ti-Mg alloy were systematically studied.METHODS: The Mg powder and 17 powder in different mass ratios were prepared by powder metallurgy process to get a new integrated medical Ti-Mg alloy with excellent comprehensive properties. The porosity, fracture surface morphology and phase constituents of samples were observed by optical microscopy, scanning electron microscopy and X-ray diffraction, and the mechanical properties including bending strength, impact toughness and hardness of the alloys were measured,RESULTS AND CONCLUSION: Magnesium mass increasing firstly decreased and then increased admissible strain. When magnesium mass was 10%, admissible strain was 0.97%, which was highly closed to 0.67% of cortical bone. The porosity decreased from 18.3% to 3.8%, the holes became more tact and distributes more uniform, with the increased of mass ratio of magnesium. And with the increased of mass ratio of magnesium, the hardness, bending strength and elastic modulus of alloys with similar pattern of change, there were little changed when the mass fraction of magnesium less than 10%, they decreased significantly and then tended to stable with the continued to increased of magnesium mass fraction. While the admissible strain firstly decreased and then increased, with the increased of the mass fraction of magnesium. When the mass fraction of magnesium was 10%, the hardness, bending strength, impact toughness satisfied the mechanical requirements for human body implants, and the bending strength and admissible strain were close to human bones, which indicated well biomechanical compatibility.
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To evaluate the acute lung toxicity of intratracheally instilled nano-TiO2 in Kunming mice, healthy adult male Kunming mice were randomly grouped by their body weight (5 mice in each group). The lungs of mice were intratracheally instilled with 1 or 10 mg/kg x bw of nano-TiO2. The control group was intratracheally instilled with the same volume of physiological saline. After 1 d, 7 d, 14 d and 28 d of exposure, the bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The indices of BALF were examined. Lung tissues were assess histopathologically. The results showed that all indices of 10 mg/kg x bw groups were obviously higher than those of the control group and the group of nano-1 mg/kg x bw, respectively. Activities of lactate dehydrogenase (LDH) on the 1st, 7th, 14th and 28th day post-exposure (pe), the amounts of malodialdehyde (MDA) on the 1st, 7th and, 14th day pe and total protein (TP) on the 1st and 7th day pe as well as the amounts of leukocyte on the 1st and 7th day pe of 10 mg/kg x bw groups were significantly different as compared with controls (P < 0.05). There were no obvious changes observed in the activity of alkaline phosphatase (ALP) within groups (P > 0.05). Histopathological examination revealed that the lungs of 10 mg/kg x bw groups presented marked increase in pulmonary inflammation. Many TiO2 particles were still clearly found in the interstitium at 28 days pe. In contrast, low-dose instillation put forward a low risk potential for producing adverse effects on pulmonary health. We conclude that the inflammatory reaction gradually ceased after 28 days. Under the same experimental condition, the effect of lung injury was severer in high-dose nano-TiO2 than in low-dose nano-TiO2.
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Animals , Male , Mice , Bronchoalveolar Lavage Fluid , Cell Biology , Lung , Pathology , Metal Nanoparticles , Toxicity , Random Allocation , Titanium , Toxicity , Toxicity Tests, AcuteABSTRACT
High density, well ordered and uniform titanium oxide nanotube arrays were fabricated on the surface of titanium substrate by anodic oxidation in 0.5 mol/L H3P04 + 0. 138 mol/L NaF solution. Then hydroxyapatite coatings were deposited in a simulated body fluid (SBF). The morphology of titanium oxide nanotubes and the coatings was observed by means of scanning electron microscope (SEM). The phase composition of the coatings was determined by X-ray diffractometer (XRD). The phenomenon of polarization was studied by the CHI660A Electrochemical Workstation. The titanium oxide nanotube was found to be about 100 nm in diameter. The result of the samples soaked in SBF showed that the hydroxyapatite coatings were precipitated on the nanotube of titanium oxide.