PLCE1 inhibits apoptosis of non-small cell lung cancer via promoting PTEN methylation.

OBJECTIVE: To explore the role of phospholipase C epsilon 1 (PLCE1) in regulating cell apoptosis of non-small cell lung cancer (NSCLC) and its underlying mechanism. PATIENTS AND METHODS: The mRNA and protein levels of PLCE1 in NSCLC tissues, adjacent normal tissues and NSCLC cell lines (A549 and H1299) were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. Methylation status in the promoter region of PTEN in NSCLC cells was accessed using the relative commercial kit. Cell apoptosis after transfection of PLCE1 siRNA in NSCLC cells was detected by flow cytometry. Protein expressions of apoptosis-related genes in NSCLC cells after altering PLCE1 expression were detected by Western blot. RESULTS: PLCE1 was highly expressed in NSCLC tissues and cell lines than that of controls. PLCE1 knockdown promoted PTEN expression and inhibited methylation in H1299 cells. Transfection of PLCE1 siRNA in NSCLC cells remarkably induced cell apoptosis. CONCLUSIONS: PLCE1 inhibits cell apoptosis of NSCLC by promoting PTEN methylation.

Effects of Linc00460 on cell migration and invasion through regulating epithelial-mesenchymal transition (EMT) in non-small cell lung cancer.

OBJECTIVE: To detect the relative expression of long intergenic non-protein coding RNA 460 (linc00460) in non-small cell lung cancer (NSCLC) tissues and cells, to investigate the effects of linc00460 on proliferation, migration and invasion of NSCLC and to preliminarily explore its potential molecular action mechanisms. PATIENTS AND METHODS: The relative expression of cancer tissues from 52 patients with NSCLC compared with that of para-carcinoma normal tissues was detected through Real-time quantitative polymerase chain reaction (qRT-PCR). qRT-PCR was also used to test the relative expressions of linc00460 in 4 strains of NSCLC cells. Effects of knockdown of linc00460 expression on the cell proliferation ability were detected by cell counting kit-8 (CCK-8) assay through transfection of small interfering linc00460 (si-linc00460) interference sequence in A549 cells and PC-9 cells. Transwell assay was used to detect the effects of lic00460 on the migration and invasion abilities of NSCLC cells. Western blot was applied to observe the changes of epithelial-mesenchymal transition (EMT)-related proteins. The expression changes of EMT-related proteins were detected by immunofluorescence assay. RESULTS: qRT-PCR results showed that there were 40 cases (76.9%) with up-regulated linc00460 expressions in tissues from 52 patients with NSCLC. The linc00460 expressions in 5 strains of NSCLC cells were higher than those of human bronchial epithelial (16HBE) cells. Interference in linc00460 expression could inhibit the proliferation, invasion and migration of NSCLC cells. Results of Western blot and immunofluorescence found that interfering with the linc00460 expression could affect the expression changes of EMT-related proteins. CONCLUSIONS: The relative expression of linc00460 is upregulated in NSCLC tissues. Cells and linc00460 can promote the tumor invasion and migration through affecting EMT.

Phenotype standardization of angioedema in the head and neck region caused by agents acting on the angiotensin system.

Angioedema is a potentially life-threatening adverse reaction to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. To study the genetic etiology of this rare adverse event, international consortia and multicenter recruitment of patients are needed. To reduce patient heterogeneity, we have standardized the phenotype. In brief, it comprises swelling in the head and neck region that first occurs during treatment. It should not coincide with urticaria or have another likely cause such as hereditary angioedema.

Phenotype standardization for statin-induced myotoxicity.

Statins are widely used lipid-lowering drugs that are effective in reducing cardiovascular disease risk. Although they are generally well tolerated, they can cause muscle toxicity, which can lead to severe rhabdomyolysis. Research in this area has been hampered to some extent by the lack of standardized nomenclature and phenotypic definitions. We have used numerical and descriptive classifications and developed an algorithm to define statin-related myotoxicity phenotypes, including myalgia, myopathy, rhabdomyolysis, and necrotizing autoimmune myopathy.

Preparation and characterization of novel polytitanium tetrachloride coagulant for water purification.

Polymeric metal coagulants are increasingly being used to improve coagulation efficiency, yet the research on the development of titanium and particularly polytitanium salts remains limited. This study is the first attempt in the synthesis, characterization, and application of polytitanium salts as coagulants. Polytitanium tetrachloride (PTC) solutions with different basicity values B (OH/Ti molar ratio) were prepared using a slow alkaline titration method. Jar tests were conducted to assess coagulation performance using both synthetic and real raw water samples, and the floc characteristics were monitored online using a laser diffraction particle size analyzer. Electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) was utilized to identify various Ti species, with the results providing strong evidence of the presence of various hydrolyzed Ti species in the titanium aqueous phase. Compared to titanium tetrachloride (TiCl4), higher or comparable turbidity and organic matter removal efficiency could be achieved by PTC with improved floc characteristics in terms of size, growth rate, and structure. Besides, the water pH after PTC coagulation was significantly improved toward neutral pH. This study indicates that PTC is an effective and promising coagulant for water purification. Besides, the PTC flocculated sludge was able to recycle and produce functional TiO2 photocatalyst.

Applicability of agricultural waste and by-products for adsorptive removal of heavy metals from wastewater.

This critical review discusses the potential use of agricultural waste based biosorbents (AWBs) for sequestering heavy metals in terms of their adsorption capacities, binding mechanisms, operating factors and pretreatment methods. The literature survey indicates that AWBs have shown equal or even greater adsorption capacities compared to conventional adsorbents. Thanks to modern molecular biotechnologies, the roles of functional groups in biosorption process are better understood. Of process factors, pH appears to be the most influential. In most cases, chemical pretreatments bring about an obvious improvement in metal uptake capacity. However, there are still several gaps, which require further investigation, such as (i) searching for novel, multi-function AWBs, (ii) developing cost-effective modification methods and (iii) assessing AWBs under multi-metal and real wastewater systems. Once these challenges are settled, the replacement of traditional adsorbents by AWBs in decontaminating heavy metals from wastewater can be expected in the future.

Cationic polyacrylamide as coagulant aid with titanium tetrachloride for low molecule organic matter removal.

This is the first attempt to use cationic polyacrylamide (PAM) as coagulant aid with titanium tetrachloride (TiCl4) to improve the coagulation performance and floc properties. Coagulation-flocculation treatment was applied to simulated water (with fulvic acid (FA) as model organic matter) for both coagulation behavior investigation and floc characterization. The effect of PAM on floc reformation properties after cyclic breakage/regrowth was also investigated. Ultrafiltration experiments were performed to investigate the influence of PAM aided TiCl4 coagulation on the membrane fouling. The results showed that organic removal was enhanced by PAM addition at low TiCl4 doses. Floc growth rate and floc size were significantly affected by dosing sequence. TiCl4-PAM significantly improved the floc strength factors (Sf) and recovery factors (Rf). The dosing sequence of TiCl4 and PAM significantly influenced the floc structure. Characterization of the flocculated sludge indicated that TiO2 with anatase structure and high photocatalytic activity could be obtained from the TiCl4-PAM flocculated sludge.

Anionic polymer compound bioflocculant as a coagulant aid with aluminum sulfate and titanium tetrachloride.

The objectives of this study are to investigate the impacts of anionic polymer compound bioflocculant (CBF) as a coagulant aid on coagulation performance and floc characteristics with titanium tetrachloride (TiCl(4)) and aluminum sulfate (Al(2)(SO(4))(3)). The effect of dosing sequence was also investigated. Floc size, breakage, regrowth and floc fractal dimension were examined using a laser diffraction instrument. The results showed that CBF with TiCl(4) or Al(2)(SO(4))(3) coagulants exhibited synergistic effects by promoting dissolved organic carbon (DOC) removal. For both TiCl(4) and Al(2)(SO(4))(3), the floc recoverability was improved by CBF addition, and the flocs formed by TiCl(4) and the corresponding dual-coagulants showed weaker recovery ability than those by Al(2)(SO(4))(3) and the corresponding dual-coagulants. Fractal dimension analysis demonstrated that the floc fractal dimension values increased with the increasing coagulant dose. The effect of CBF on fractal dimension of the flocs generated by TiCl(4) was different from that of Al(2)(SO(4))(3).

The effect of second coagulant dose on the regrowth of flocs formed by charge neutralization and sweep coagulation using titanium tetrachloride (TiCl4).

Characteristics of flocs formed by charge neutralization and sweep coagulation using titanium tetrachloride (TiCl(4)) were investigated with humic acid-kaolin suspension by continuous optical monitoring. This paper focused on the regrowth ability of broken flocs after addition of second TiCl(4) dose. Variation of floc size and the fractal dimension of flocs versus second TiCl(4) dose after regrowth were investigated. Second TiCl(4) dose was added during the floc breakage period, and addition time of second TiCl(4) dose was also investigated. The results showed that, when coagulated by charge neutralization at pH 6, an appropriate second TiCl(4) dose improved regrowth ability of broken flocs at low initial TiCl(4) doses. While for high initial TiCl(4) doses, second TiCl(4) dose lowered floc re-growth ability. When coagulated by sweep coagulation at pH 10, second TiCl(4) dose made regrown flocs larger than those without second TiCl(4) dose. Floc structure analysis showed that it was determined by not only the fractal dimension of flocs, but also the chemical characteristics of floc surface. Addition time of second TiCl(4) dose had a great effect on floc regrowth ability, suggesting that the broken flocs had better regrowth when second TiCl(4) dose was added at the end of the breakage period.

Effect of shear force, solution pH and breakage period on characteristics of flocs formed by Titanium tetrachloride (TiCl4) and Polyaluminum chloride (PACl) with surface water treatment.

The growth, breakage and regrowth nature of flocs formed by Titanium tetrachloride (TiCl(4)) and polyaluminum chloride (PACl) was comparatively evaluated with surface water treatment. A series of jar experiments were conducted to investigate the impacts of different operating parameters such as shear force, solution pH and a breakage period on floc strength and re-aggregation potential. Results indicated that the responses of flocs to different operating parameters depend on the coagulant used. The ability of floc to resist breakage decreased with the increase of shear force and breakage period. Floc strength properties were also measured in response to increasing shear force, with the results suggesting that the order of floc strength was TiCl(4)>PACl. Floc regrowth of the two coagulants after exposure to high shear was limited, and flocs formed by TiCl(4) displayed weaker recoverability. The flocs generated in acid conditions were more recoverable than those generated in alkaline conditions no matter which coagulant was used.

Clinically significant CYP2C inhibition by noscapine but not by glucosamine.

Noscapine and glucosamine reportedly interact with warfarin. We investigated the effects of these drugs on various cytochrome P450 (CYP) activity markers. Twelve healthy subjects were phenotyped at baseline and during separate treatments with noscapine and glucosamine. Whereas glucosamine had no significant effect on CYP activity, noscapine caused marked inhibition of CYP2C9 (4.9-fold increase in urinary losartan/E3174 ratio) and CYP2C19 (3.6-fold increase in the plasma omeprazole/5-hydroxyomeprazole ratio). Noscapine-dependent inhibition of CYP2C9 may explain the interaction with warfarin.

Strength and regrowth properties of polyferric-polymer dual-coagulant flocs in surface water treatment.

The floc strength and regrowth properties of three polyferric-cationic polymer dual-coagulants were comparatively evaluated using surface water sample. The first dual-coagulant PFC-PD was prepared by premixing of polyferric chloride (PFC) and polydiallyldimethylammonium (PDADMAC) before dosing. The other two, PFCF (PFC dosed firstly) and PDF (PDADMAC dosed firstly), were achieved by dosing PFC and PDADMAC in different order. Floc strength properties were measured in response to increasing shear levels in the long period and high shear level in the short or long period. For the given optimum dose (3.0 mg L(-1)) and water pH (6.5) condition, the order of floc strength was PFCF>PDF>PFC-PD. The dual-coagulant which gave stronger flocs also gave a lower absolute value of zeta potential. The floc regrowth properties of all three dual-coagulants after short and long period high shear level were also investigated. The floc recoverability was in the following order: PFCF>PFC-PD>PDF.

Performance and mechanism of polyferric-quaternary ammonium salt composite flocculants in treating high organic matter and high alkalinity surface water.

A series of composite flocculants PFC-PD with different basicity (B) of polyferric chloride (PFC), different weight percentage (w(P)) and intrinsic viscosity (eta) of polydimethyl diallylammonium chloride (PDMDAAC) were prepared by prepolymerization. The turbidity, dissolved organic carbon (DOC) and specific ultraviolet absorbance (SUVA) removal efficiency as well as flocculation mechanism of PFC-PD were compared with that of PFC, PDMDAAC and successive addition of PFC and PDMDAAC in treating high DOC and high alkalinity surface water by jar tests. The effect of B, w(P) and eta on coagulation efficiency and mechanisms were also studied. The experimental results showed that PFC-PD was more efficient and more applicable for turbidity, DOC and SUVA removal than PFC, PDMDAAC and successive addition of PFC and PDMDAAC. Further, the water pH was slightly depressed by PFC-PD. Coagulation efficiency of PFC-PD was improved at lower B, larger w(P) and larger eta. Charge neutralization was dominant mechanism of PFC-PD.

Synthesis of polyamine flocculants and their potential use in treating dye wastewater.

Polyamine flocculants were synthesized by the polycondensation of dimethylamine and epichlorohydrin, in which organic amines, e.g. 1,2-diaminoethane, were used as modifying agents. Different products were obtained by varying the reaction parameters, such as the molar ratio of epichlorohydrin to dimethylamine, the amount of 1,2-diaminoethane and reaction temperature. The polyamine flocculants were characterized by transmission electron microscope (TEM). Their flocculation performance was evaluated with simulated dye liquor and actual printing and dyeing wastewater. The behavior of the flocculants was compared with that of inorganic coagulant, polyaluminum chloride (PAC). The experimental results show that polyamine with the highest viscosity and cationicity could be prepared under following conditions: an epichlorohydrin to dimethylamine molar ratio of 1.5, a reaction temperature of 70 degrees C, a 3% content of 1,2-diaminoethane in the total reaction monomers and a reaction time of 7h. Polyamine polymers can, as flocculants for treating simulated and actual dye wastewater, remove color and COD efficiently. The rate of color removal from reactive red liquor, reactive blue liquor and reductive yellow liquor reached as high as 96%, 97% and 96%, respectively. The highest efficiency of color removal and COD removal from polyamine for treating dye wastewater was 90% and 89%, respectively.

Color removal from textile industry wastewater using composite flocculants.

In this study, the decolorization of textile wastewater using composite flocculants was examined. It was composed of Fe(III) flocculants and polydimethyldiallylammonium chloride (PDMDAAC). The color removal efficiency of the composite flocculants was compared with that of individual flocculants, ferric chloride (FeCl3), polyferric chloride (PFC) and PDMDAAC, respectively. The results showed that the composite flocculants were more efficient than individual ones in color removal. The color removal efficiency of the composite flocculants was found to be related to the weight percentage of PDMDAAC (Wp), basicity (B) of PFC and molecular weight (MW) of PDMDAAC. The removal rate is higher at a larger Wp and MW value and lower B value. Chemical oxygen demand (COD) removal from textile wastewater was also investigated in this study. During color removal by the composite flocculants, only up to 20% COD could be removed from the textile wastewater. FeCl3 was then used to further remove the remaining COD from the decolorized wastewater. This two-step treatment of textile wastewater could achieve a 91.6% reduction in COD and an 88.9% reduction in color.

The performance and application of fly ash modified by PDMDAAC.

Fly ash modification by polydimethydiallylammonium chloride (PDMDAAC) in laboratory scale was explored in this work and the adsorption performance of modified fly ash and its application in dyeing wastewater treatment were also studied. The key factors (concentration and temperature) for PDMDAAC to affect the adsorption properties of fly ash (FA) were revealed using the orthogonal test with four factors. The results indicated that the adsorption magnitude of fly ash to PDMDAAC increased due to its favorable specific surface causing the change of the surface charge nature. Hence, adsorption performance of modified fly ash on organic molecules and its ion exchange capacity are strengthened. The maximum color removal efficiency was obtained as 88.2% by modified fly ash with 2.0 g/100 mL dosage in dyeing wastewater, which is much higher than 12.5% color removal efficiency by raw fly ash with the same dosage. And, the used modified fly ash could be used for cement production as additive agent. The intensity of cement produced with 15% the modified fly ash in weight reached the Chinese Cement Standard (GB/T17671-1999), blazing a promising novel way in fly ash utilization.

Warfarin sensitivity related to CYP2C9, CYP3A5, ABCB1 (MDR1) and other factors.

The required dose of the oral anticoagulant warfarin varies greatly, and overdosing often leads to bleeding. Warfarin is metabolised by cytochrome P450 enzymes CYP2C9, CYP1A2 and CYP3A. The target cell level of warfarin may be dependent on the efflux pump P-glycoprotein, encoded by the adenosine triphosphate-binding cassette gene ABCB1 (multidrug resistance gene 1). Genetic variability in CYP2C9, CYP3A5 and ABCB1 was analysed in 201 stable warfarin-treated patients using solid-phase minisequencing, pyrosequencing and SNaPshot. CYP2C9 variants, age, weight, concurrent drug treatment and indication for treatment significantly influenced warfarin dosing in these patients, explaining 29% of the variation in dose. CYP3A5 did not affect warfarin dosing. An ABCB1 haplotype containing the exon 26 3435T variant was over-represented among low-dose patients. Thirty-six patients with serious bleeding complications had higher prothrombin time international normalised ratios than 189 warfarin-treated patients without serious bleeding, but there were no significant differences in CYP2C9, CYP3A5 or ABCB1 genotypes and allelic variants.

St John's wort (Hypericum perforatum): drug interactions and clinical outcomes.

AIMS: The aim of this work is to identify the medicines which interact with the herbal remedy St John's wort (SJW), and the mechanisms responsible. METHODS: A systematic review of all the available evidence, including worldwide published literature and spontaneous case reports provided by healthcare professionals and regulatory authorities within Europe has been undertaken. RESULTS: A number of clinically significant interactions have been identified with prescribed medicines including warfarin, phenprocoumon, cyclosporin, HIV protease inhibitors, theophylline, digoxin and oral contraceptives resulting in a decrease in concentration or effect of the medicines. These interactions are probably due to the induction of cytochrome P450 isoenzymes CYP3A4, CYP2C9, CYP1A2 and the transport protein P-glycoprotein by constituent(s) in SJW. The degree of induction is unpredictable due to factors such as the variable quality and quantity of constituent(s) in SJW preparations. In addition, possible pharmacodynamic interactions with selective serotonin re-uptake inhibitors and serotonin (5-HT(1d)) receptor-agonists such as triptans used to treat migraine were identified. These interactions are associated with an increased risk of adverse reactions. CONCLUSIONS: In Sweden and the UK the potential risks to patients were judged to be significant and therefore information about the interactions was provided to health care professionals and patients. The product information of the licensed medicines involved has been amended to reflect these newly identified interactions and SJW preparations have been voluntarily labelled with appropriate warnings.

Distribution of aluminum species and the characteristics of structure of poly-aluminum-chloride-sulfate(PACS).

A series of poly-aluminum-chloride-sulfate (PACS), which has different basicities (gamma) and Al3+/SO4(2-) molar ratio, has been prepared and dried at 105 degrees C and 65 degrees C, respectively. The distribution of aluminum species of PACS was examined, and the effect of gamma value, Al3+/SO4(2-) molar ratio, dilution on the distribution of aluminum species of PACS was also investigated by using Alferron timed complex colorimetric method. The IR spectroscopy and X-ray diffraction were used to study the effect of gamma value, Al3+/SO4(2-) molar ratio and the drying temperature on the structure of PACS. The experimental results show that Al3+/SO4(2-) molar ratio has a great effect on the distribution of aluminum species, but the dilution has a little effect on the distribution of aluminum species. The lower the Al3+/SO4(2-) molar ratio, the higher the proportions of the polymer and colloidal species in PACS. The polymeric degree of PACS was related to gamma value and Al3+/SO4(2-) molar ratio. Drying temperature has an influence on the structure and the solubility of solid PACS products.