Celecoxib enhances the response of tumor cells to cisplatin through upregulating PUMA in non–small cell lung cancer carrying wild-type p53

Celecoxib,a cyclooxygenase-2 inhibitor,can enhance the efficacy of chemotherapy;however,its effect seems inconsistent.In this study,we investigated whether celecoxib would increase the antiproliferative effects of cisplatin in human lung cancer cells.Our data demonstrated the synergistic effects of celecoxib with cisplatin in wild-type p53 cells and their antagonistic effects inmutated or deleted p53 cells.Combination indices of 0.82 to 0.93 reflected a synergistic effect between celecoxib and cisplatin in lung cancer cells with wild-type p53.Combination indices of 1.63 to 3.00 reflected antagonism between celecoxib and cisplatin in lung cancer cells with mutated or deleted p53.Compared with that in cells with mutated or deleted p53,apoptosis significantly increased with the addition of celecoxib and cisplatin in wild-type p53 cells(P<0.05).Moreover,the results in vivo were similar to those in vitro:celecoxib combinedwith cisplatin slowed tumor growth in wild-type p53 groups and not in mutated or deleted p53 groups.In addition,celecoxib promoted p53 translocation into the nucleus and upregulated active p53 expression in wild-type p53 cells.Celecoxib combined with cisplatin upregulated PUMA(PUMA is a downstream gene of p53)after active p53 increased in wild-type p53 cells.In summary,the combination of celecoxib and cisplatin demonstrates clear synergistic effects in wild-type p53 cells and antagonistic effects inmutated or deleted p53 cells.The synergistic effect was achieved by apoptosis,induced by upregulating PUMA.Our results will provide a new treatment strategy for patients carrying wild-type p53,insensitive to cisplatin.

The expression of vascular endothelial growth factor(VEGF)/endostatin(ES)and VEGF receptor 2(VEGFR2)/ES is associated with NSCLC prognosis

Objective The aim of our study was to detect the expression of angiogenesis inhibitory proteins and angiogenesis promotive proteins in the postoperative tumor tissue of non-small cell lung cancer(NSCLC)patients.We also investigated the relationship of protein expression with clinical characteristics and prognosis.Methods We examined the expression of vascular endothelial growth factor(VEGF),VEGF receptor 2(VEGFR2),and endostatin(ES)proteins in 255 specimens resected from NSCLC patients,using immune histochemistry(IHC).We then evaluated the relationships between the expression of the three proteins and clinical characteristics such as stage,histological type,differentiation,gender,tobacco use,and age.According to the value of VEGF/ES,we divided the cohort into angiogenesis-promoting group A,angiogenesis-inhibiting group A,and balance group A.The survival differences in the three groups were evaluated to determine the prognostic value of VEGF/ES.Similarly,we tested the prognostic value of VEGFR2/ES.Results VEGF-positive expression was observed in 93 patients(36.4%).VEGF expression was not correlated with the clinical characteristics.VEGFR2-positive expression was observed in 103 patients(40.4%).The expression of VEGFR2 was correlated with the clinical stage(χ^(2)=21.414,P=0.045)and histological type(χ^(2)=26.911,P=0.008).ES-positive expression was observed in 140 patients(54.9%).The expression of ES was correlated with the clinical stage(χ^(2)=26.504,P=0.009).When evaluating the prognostic values of VEGF/ES and VEGFR2/ES,the prognosis of the angiogenesis balance group was similar to that of the angiogenesis-inhibiting group.The minimum survival time was observed in the angiogenesis-promoting group.Conclusion VEGF/ES and VEGFR2/ES in resected tumors have prognostic value in postoperative NSCLC patients.The survival time of the population with predominant angiogenic factors was short.

Trifunctional Cu-Mesh/Cu_(2)O@FeO Nanoarrays for Highly Efficient Degradation of Antibiotic, Inactivation of Antibiotic-Resistant Bacteria, and Damage of Antibiotics Resistance Genes

Trifunctional Cu-mesh/Cu_(2)O@FeO nanoarrays heterostructure is designed and fabricated by integrating CuCu_(2)O@FeO nanoarrays onto Cu-mesh(CM)via an in situ growth and phase transformation process.It is successfully applied to efficiently mitigate the antibiotic pollution,including degradation of antibiotics,inactivation of antibiotic-resistant bacteria(ARB),and damage of antibiotics resistance genes(ARGs).Under visible-light irradiation,CM/CuCu_(2)O@FeO nanoarrays exhibit a superior degradation efficiency on antibiotics(e.g.,up to 99%in 25 min for tetracycline hydrochloride,TC),due to the generated reactive oxygen species(ROS),especially the dominant·O^(2−).It can fully inactivate E.coli(HB101)with initial number of~108 CFU mL^(−1) in 10 min,which is mainly attributed to the synergistic effects of 1D nanostructure,dissolved metal ions,and generated ROS.Meanwhile,it is able to damage ARGs after 180 min of photodegradation,including tetA(vs TC)of 3.3 log 10,aphA(vs kanamycin sulfate,KAN)of 3.4 log 10,and tnpA(vs ampicillin,AMP)of 4.4 log 10,respectively.This work explores a green way for treating antibiotic pollution under visible light.

Association of genetic polymorphisms of GSTM1 and smoking status with lung cancer risk

Objective Long-term cigarette smoke exposure damages the airway epithelium.However,the correlation among GSTM1 gene polymorphism,smoking status,and lung cancer susceptibility remains unclear.This study aimed to identify the genetic polymorphism of GSTM1 and examine the association of GSTM1 polymorphism and smoking history with lung cancer susceptibility.Methods The genetic polymorphism of GSTM1 was genotyped by polymerase chain reaction(PCR) in 217 lung cancer patients and 198 controls.The demographic data and smoking history of the patients were collected.The age,sex,and residence of the two groups were also obtained.Results Significant differences in GSTM1 polymorphism were observed between the case and control groups(P=0.024).Smoking time and smoking index were significantly different between the case and control groups.With the increase in smoking time and smoking index,the differences became more obvious.There was a synergistic effect between GSTM1 and smoking(S=3.35).The risk of developing lung cancer increased 4.82 fold in smokers carrying deficient-type GSTM1.Compared with patients carrying wild-type GSTM1,the risk of developing lung cancer was higher in those carrying deficient-type GSTM1 with the increase in smoking time and smoking index.In different pathological types,no significant differences were observed in GSTM1 polymorphism.In different pathological types,the proportions of patients increased with the increase in smoking time and smoking index,especially the proportion of patients with squamous cell carcinoma.Compared with wild-type GSTM1,the proportion of patients with deficient-type GSTM1 increased with the increase in smoking time and smoking index(P=0.003 and 0.017).This trend was mainly observed in those with squamous cell carcinoma.Conclusion GSTM1 mutation is associated with lung cancer susceptibility.Smokers carrying deficienttype GSTM1 are more likely to develop lung cancer.Compared with patients carrying wild-type GSTM1,smokers with deficient-type GSTM1 are more likely develop lung cancer when smoking time is more than 30 years and smoking index is more than 400.In patients carrying deficient-type GSTM1,the risk of developing squamous cell carcinoma increases with an increase in smoking time and smoking dose.

Cisplatin selects for CD133+cells in lung cancer cells

Objective Platinum-based chemotherapy is the first-line treatment for non-small cell lung cancer,but the chemoresistance of tumor cells continues to be a considerable challenge in the management of NSCLCs,leading to recurrence of most patients.CD133(prominin-1)is a five-transmembrane glycoprotein,and recent evidence suggests that CD133+cells are the cause of drug resistance and tumor recurrence.In this study,the correlation between cisplatin and CD133+cells was investigated systematically.Methods Four lung cancer cell lines,including A549,H460,801D and H1299,were treated with different concentrations of cisplatin.Cell viability was determined by MTT assay.Sphere-forming assay was performed to detect the capability of sphere-forming.CD133+cells was detected by BD FACScaliber flow cytometer.Results The results showed that cisplatin could increase the number of CD133+cells in both time-and dose-dependent manner.The enrichment would weaken but the proportion of CD133+cells was still higher than the basic level as incubation time extended after cisplatin was withdrawn.Compared with adherent culture,the proportion of CD133+cells was higher when the cells were maintained suspension culture.The proportion of CD133+cells significantly increased when cisplatin was provided in suspension culture.Conclusion These results revealed that cisplatin induces the enrichment of CD133+cells and CD133 is a new therapeutic target.Our data partially explained drug resistance to second-line chemotherapy in cisplatin-treated patients with NSCLCs.

环氧化酶-2在人肺癌中的表达及其意义(英文)

Objective: We aimed to examine the expression of cyclooxygenase-2 and the relationship with the pathological types, TNM stage, lymph node metastasis, the degree of differentiation, smoking and the survival. Methods: Immunohistochemical staining method was used to examine the expression of cyclooxygenase-2 of 121 cases of lung cancer and three control groups. The data were statistically analyzed. Results: Compared with the health group, cyclooxygenase-2 was over expressed in the inflammatory tissue(P = 0.036), lung adenocarcinoma(P = 0.005) and squamous carcinoma(P = 0.047). Compared with patients without lymph node metastasis, cyclooxygenase-2 was over expressed(P = 0.033) in patients with lymph node metastasis. Compared with high differentiation group, cyclooxygenase-2 was over expressed(P = 0.004) in low differentiation group. Compared with non-smokers, the expression of cyclooxygenase-2 increased in smokers(P = 0.000). The median survival time of patients that the expression of cyclooxygenase-2 were negative was 9 months(95% CI, 5.6–12.4 months). The median survival time of patients that the expression of cyclooxygenase-2 were positive was 5 months(95% CI, 3–7 months). They was statistical difference(P = 0.001). Conclusion: Overexpression of cyclooxygenase-2 is associated with pathological types, TNM stage, lymph node metastasis, degrees of differentiation, smoking and prognosis in lung cancer.

Preparation and characterization of poly （vinylidene fluoride）/ Ti02 hybrid membranes

Poly（vinylidene fluoride） （PVDF）/titanium dioxide （TiO2） hybrid membranes were prepared using nano-TiO2 as the modifier, and characterized by Transmis- sion Electron Microscope （TEM）, Fourier transform infrared spectroscopy （FT-IR）, scanning electron micro- scope （SEM）, atomic force microscope （AFM）, X-ray diffraction （XRD） and X-ray photoelectron spectroscopy （XPS）. The characterization results demonstrated that nano-sized TiO2 particles dispersed homogeneously within the PVDF matrix, contributing to more hydroxyls and smoother surfaces. Moreover, permeate flux, retention factor, porosity, contact angle and anti-fouling tests were carried out to evaluate the effect of TiO2 concentration on the performance of PVDF membranes. Among all the prepared membranes, PVDF/TiO2 membrane containing 10 vol.% TiO2 exhibited the best hydrophilicity with an average pure water flux up to 237 L.mE.h1, higher than that of unmodified PVDF membranes （155L.m2.h ）. Besides, the bovine serum albumin rejection of the hybrid membrane was improved evidently from 52.3% to 70.6%, and the contact angle was significantly lowered from 83° to 60°, while the average pore size and its distribution became smaller and narrower.

Presence, dissemination and removal of antibiotic resistant bacteria and antibiotic resistance genes in urban drinking water system: A review

Antibiotic resistance in aquatic environment has become an important pollution problem worldwide. In recent years, much attention was paid to antibiotic resistance in urban drinking water systems due to its close relationship with the biosafety of drinking water. This review was focused on the mechanisms of antibiotic resistance, as well as the presence, dissemination and removal of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in the urban drinking water system. First, the presence of ARB and ARGs in the drinking water source was discussed. The variation of concentration of ARGs and ARB during coagulation, sedimentation and filtration process were provided subsequently, in which filtration was proved to be a promising technology to remove ARGs. However, biological activated carbon (BAC) process and drinking water distribution systems (DWDSs) could be incubators which promote the antibiotic resistance, due to the enrichment of ARGs and ARB in the biofilms attached to the active carbon and pipe wall. Besides, as for disinfection process, mechanisms of the inactivation of ARB and the promotion of conjugative transfer of ARGs under chlorine, ozone and UV disinfection were described in detail. Here we provide some theoretical support for future researches which aim at antibiotic resistance controlling in drinking water.

Effect of biological activated carbon filter depth and backwashing process on transformation of biofilm community

The biological activated carbon (BAC) is a popular advanced water treatment to the provision of safe water supply. A bench-scale device was designed to gain a better insight into microbial diversity and community structure of BAC biofilm by using high-throughput sequencing method. Both samples of BAC biofilm (the first, third and fifth month) and water (inlet water and outlet water of carbon filter, outlet water of backwashing) were analyzed to evaluate the impact of carbon filter depth, running time and backwash process. The results showed that the microbial diversity of biofilm decreased generally with the increase of carbon filter depth and biofilm reached a steady-state at the top layer of BAC after three months' running. Proteobacteria (71.02%-95.61%) was found to be dominant bacteria both in biofilms and water samples. As one of opportunistic pathogen, the Pseudomonas aeruginosa in the outlet water of device (1.20%) was about eight times higher than that in the inlet water of device (0.16%) at the genus level after five-month operation. To maintain the safety of drinking water, the backwash used in this test could significantly remove Sphingobacteria (from 8.69% to 5.09%, p < 0.05) of carbon biofilm. After backwashing, the operational taxonomic units (OTUs) number and the Shannon index decreased significantly (p <0.05) at the bottom of carbon column and we found the Proteobacteria increased by about 10% in all biofilm samples from different filter depth. This study reveals the transformation of BAC biofilm with the impact of running time and backwashing.

Layered CuNi-Cu_(2)O/NiAlO_(x) nanocatalyst for rapid conversion of p-nitrophenol to p-aminophenol

In order to well arrange active sites and avoid byproducts, the reasonable structured carrier nanocatalyst plays a crucial role in high catalytic performance, but still remains a challenge. Herein, the layered CuNi-Cu_(2)O/NiAlO_(x) nanosheets have been constructed through hydrothermal synthesis followed by calcination and H_(2) reduction treatment process. The in-situ formed CuNi nanoalloys (NAs) and nano-Cu_(2)O were evenly distributed on the bilateral surface of layered NiAlOx nanosheets. Based on the planar structure of nanosheet, the synergy between catalytic active CuNi NAs and photocatalytic active nano-Cu_(2)O endows CuNi-Cu_(2)O/NiAlO_(x) nanosheets with rapid conversion efficiency for catalyzing p-nitrophenol (p-NP, 14 mg·L^(−1)) to p-aminophenol (p-AP) in 32 s with the reaction rate constant k up to 0.1779 s−1, and no obvious performance decay can be observed even over 27 cycles. Moreover, high concentration of p-NP at 10 and 20 g·L^(−1) could be reduced to p-AP within 14 and 20 min, respectively. Such designed nanoalloy/bimetal-oxide heterostructure can provide a solution for rapid conversion of aminoaromatics from nitroaromatics wastewater even at a large concentration range.

Synergistic effects of sodium hypochlorite disinfection and iron-oxidizing bacteria on early corrosion in cast iron pipes

Corrosion in drinking water distribution systems(DWDSs)may lead to pipe failures and water quality deterioration;biocorrosion is the most common type.Chlorine disinfectants are widely used in DWDSs to inhibit microorganism growth,but these also promote electrochemical corrosion to a certain extent.This study explored the independent and synergistic effects of chlorine and microorganisms on pipeline corrosion.Sodium hypochlorite(NaOCl)at different concentrations(0,0.25,0.50,and 0.75 mg/L)and iron-oxidizing bacteria(IOB)were added to the reaction system,and a biofilm annular reactor(BAR)was employed to simulate operational water supply pipes and explain the composite effects.The degree of corrosion became severe with increasing NaOCl dosage.IOB accelerated the corrosion rate at an early stage,after which the reaction system gradually stabilized.When NaOCl and IOB existed together in the BAR,both synergistic and antagonistic effects occurred during the corrosion process.The AOC content increased due to the addition of NaOCl,which is conducive to bacterial regrowth.However,biofilm on cast iron coupons was greatly influenced by the disinfectant,leading to a decrease in microbial biomass over time.More research is needed to provide guidelines for pipeline corrosion control.

Molecular analysis of bacterial community in the tap water with different water ages of a drinking water distribution system

Bacterial community in the drinking water distribution system （DWDS） was regulated by multiple environmental factors, many of which varied as a function of water age. In this study, four water samples with different water ages, including finished water （FW, 0 d） and tap water （TW） [TWI （1 d）, TW2（2 d） and TW3（3 d）], were collected along with the mains of a practical DWDS, and the bacterial community was investigated by high-throughput sequencing technique. Results indicated that the residual chlorine declined with the increase of water age, accompanied by the increase of dissolved organic matter, total bacteria counts and bacterial diversity （Shannon）. For bacterial community composition, although Proteobacteria phylum （84.12%-97.6%） and Alphaproteobacteria class （67.42c/,~93.09%） kept dominate, an evident regular was observed at the order level. In detail, the relative abundance of most of other residual orders increased with different degrees from the start to the end of the DWDS, while a downward trend was uniquely observed in terms of Rhizobiales, who was inferred to be chlorine-resistant and be helpful for inhibiting pipes corrosion. Moreover, some OTUs were found to be closely related with species possessing pathogenicity and chlorine-resistant ability, so it was recommended that the use of agents other than chlorine or agents that can act synergically with chlorine should be developed for drinking water disinfection. This paper revealed bacterial community variations along the mains of the DWDS and the result was helpful for understanding bacterial ecology in the DWDS.