Improved visible light triggered photocatalytic activities of BiOCl photocatalysts via a synergistic effect of doping and heterojunction engineering.

To manipulate the photocatalytic activities of BiOCl photocatalysts, doping and heterojunction engineering are simultaneously adopted. Herein, the photocatalysts Sm3+-doped BiOCl and BiOCl:Sm3+@yg-C3N4 were designed, in which their phase structure, morphology, optical properties and photocatalytic activities were systematically discussed. Excited at 408 nm, red emissions are seen from Sm3+-doped BiOCl microplates and their intensities were impacted by doping content, reaching the maximum value when the Sm3+ content was 1 mol% and the involved concentration mechanism was dominated by quadrupole-quadrupole interaction. Through analyzing the degradation of TC, the visible light triggered photocatalytic behaviors of the resultant compounds were studied. Compared with BiOCl microplates, an improved TC removal ability was seen in Sm3+-doped BiOCl microplates and the products with a Sm3+ content of 0.5 mol% show the best performance. Moreover, through constructing the heterojunction with g-C3N4, the TC removal capacity was further enhanced and the BiOCl:Sm3+@60%g-C3N4 exhibits the optimal photocatalytic activity, which was also much better than that of the commercial SnO2 and TiO2. Accordingly, the ˙O2-, h+ and ˙OH active species were proven to contribute to the involved visible light driven photocatalytic mechanism. Furthermore, the separation and recombination of photogenerated carries via the Z-scheme transfer process in the designed heterojunction composites, led to splendid photocatalytic properties. Additionally, it was verified that the TC solution treated with synthesized compounds was nontoxic toward plant growth. Our findings may propose an available route to regulate the photocatalytic performance of the visible light driven photocatalysts.

Analgesic Effects of Repetitive Transcranial Magnetic Stimulation in Patients With Advanced Non-Small-Cell Lung Cancer: A Randomized, Sham-Controlled, Pilot Study.

Objective: Current pharmacological intervention for the cancer-related pain is still limited. The aim of this study was to explore whether repetitive transcranial magnetic stimulation (rTMS) could be an effective adjuvant therapy to reduce pain in patients with advanced non-small cell lung cancer (NSCLC). Methods: This was a randomized, sham-controlled study. A total of 41 advanced NSCLC patients with uncontrolled pain (score≥4 on pain intensity assessed with an 11-point numeric rating scale) were randomized to receive active (10 Hz, 2000 stimuli) (n = 20) or sham rTMS (n = 20) for 3 weeks. Pain was the primary outcome and was assessed with the Numeric Rating Scale (NRS). Secondary outcomes were oral morphine equivalent (OME) daily dose, quality of life (WHO Quality of Life-BREF), and psychological distress (the Hospital Depression and Anxiety Scale). All outcomes were measured at baseline, 3 days, 1 week, 2 weeks, and 3 weeks. Results: The pain intensity in both groups decreased gradually from day 3 and decreased to the lowest at the week 3, with a decrease rate of 41.09% in the rTMS group and 23.23% in the sham group. The NRS score of the rTMS group was significantly lower than that of the sham group on the week 2 (p < 0.001, Cohen's d =1.135) and week 3 (p=0.017, Cohen's d = -0.822). The OME daily dose, physiology and psychology domains of WHOQOL-BREF scores, as well as the HAM-A and HAM-D scores all were significantly improved at week 3 in rTMS group. Conclusion: Advanced NSCL patients with cancer pain treated with rTMS showed better greater pain relief, lower dosage of opioid, and better mood states and quality of life. rTMS is expected to be a new effective adjuvant therapy for cancer pain in advanced NSCLC patients.

N-{2-[(2-chlorothieno[3,2-d]pyrimidin-4-yl)amino]ethyl}-3-methoxybenzamide: design, synthesis, crystal structure, antiproliferative activity, DFT, Hirshfeld surface analysis and molecular docking study.

The compound N-{2-[(2-chlorothieno[3,2-d]pyrimidin-4-yl)amino]ethyl}-3-methoxybenzamide (8) was synthesized by the condensation of 3-methoxybenzoic acid (7) with N1-(2-chlorothieno[3,2-d]pyrimidin-4-yl)ethane-1,2-diamine (6). This intermediate was prepared from methyl 3-aminothiophene-2-carboxylate (1) by the condensation with urea, chlorination with phosphorus oxychloride and then condensation with ethane-1,2-diamine. The crystal structure of the title compound was determined and the crystal of the title compound belongs to the tetragonal system, space group P4(3) with a = 9.4694(10) Å, b = 9.4694(10) Å, c = 18.886(3) Å, α = 90°, ß = 90°, γ = 90°. The optimized geometric bond lengths and bond angles obtained by using density functional theory (DFT) have been compared with X-ray diffraction values. The calculated HOMO and LUMO energies showed the character of the title compound. The molecular electrostatic potential (MEP) surface map of the related molecule was investigated with theoretical calculations at the B3LYP/6-311 + G(d,p) levels. A quantitative analysis of the intermolecular interactions in the crystal structures has been performed using Hirshfeld surface analysis. In addition, the title compound possesses marked inhibition against the proliferation of human colon cancer cell line HT-29 (IC50 = 1.76 µM), human lung adenocarcinoma cell line A549 (IC50 = 1.98 µM) and human gastric cancer cell line MKN45 (IC50 = 2.32 µM), displaying promising anticancer activitiy. The molecular docking studies revealed that the title compound may exhibit activity inhibiting PDB:3D15.Communicated by Ramaswamy H. Sarma.

Alterations of the rhizosphere soil microbial community composition and metabolite profiles of Zea mays by polyethylene-particles of different molecular weights.

Polyethylene film is the most widely used plastic film in agricultural production activities, and its depolymerization products are mainly polyethylene-particles (PE-particles) of different molecular weights. However, the impact of the molecular weights of the PE-particles on soil-crop microenvironment has not been elucidated. In this study, a potted microcosmic simulation system was used to evaluate the impact of low, medium and high molecular weight PE-particles on soil metabolism, microbial community structure, and crop growth. There were obvious differences in the shape and surface microstructure of PE-particles with different molecular weights. Soil sucrase and peroxidase had significant responses to PE-particles of different molecular weights. In the rhizosphere, the number of microorganisms and the microbial alpha diversity index increased with increasing PE-particles molecular weight. Rhizobacter, Nitrospira, and Sphingomonas were the dominant microorganisms induced by PE-particles to regulate the metabolism of elements. Carbohydrate and amino acid contents in rhizosphere soils were the key factors affecting the species abundance of Lysobacter, Polyclovorans, Rhizobacter, and Sphingomonas. In plants, PE-particles treatment reduced the plant biomass and photosynthetic rate and disrupted normal mineral nutrient metabolism. Different molecular weight PE-particles may therefore have adverse effects on the soil-plant system.

Phytotoxicity mechanism of the natural radionuclide thorium in Vicia faba.

Elucidation of the phytotoxic mechanisms of thorium (Th) is important for controlling Th accumulation in crops and improving the efficiency of phytoremediation. Here, we analyzed the subcellular distribution of Th in Vicia faba seedlings and the toxic reaction of seedlings to Th (5-40 µmol·L-1) at the subcellular and cellular levels. Increasing the phosphate level in the culture medium from 0.01 to 0.1 mmol·L-1 decreased the Th accumulation by the roots by 47-57%. Th was mainly distributed in the root cell walls (94-96%) and existed mainly in the form of residue (92-94%). Th accumulation in the root was similar to the changes observed for P, Ni, Cu, and Fe. High concentrations of Th (40 µmol·L-1) induced abnormal root growth and leaf photosynthetic metabolism. At the cellular level, Th (40 µmol·L-1) induced root edge cell death and inhibited root respiration and cell mitosis. SOD, POD and CAT activities were involved in the regulation of reactive oxygen species accumulation in the roots. Untargeted metabolomics identified 580 and 262 differentially expressed metabolites in roots and leaves. At the metabolic level, its toxicological mechanism involved a severe inhibition of the expression of nucleotides in roots and leaves.

Unraveling response mechanism of photosynthetic metabolism and respiratory metabolism to uranium-exposure in Vicia faba.

As a natural radionuclide, uranium (U) has obvious phytotoxicity, the purpose of this study is to unravel the response mechanism of U on photosynthetic and respiratory metabolism in plants. Therefore, 14-day-old Vicia faba seedlings were exposed to 0-25 µM U during 72 h. U effects on growth parameters, physiological parameters of plants, and potential phytotoxicity mechanism were investigated by physiological analysis, and metabolome and transcriptome data. U significantly inhibited photosynthesis and respiration of plants. In metabolome analysis, 53 metabolites related to carbohydrate metabolism were identified (13 up-regulated, 12 down-regulated). In transcriptome analysis, U significantly inhibited the expression of photoreactive electron transport chain (up: 0; down: 31), Calvin cycle (up: 0; down: 12) and photorespiration pathway genes (up: 0; down: 8). U significantly inhibited the expression of cellular energy metabolic pathways genes (e.g., glycolysis, TCA cycle, and oxidative phosphorylation pathways) (up 8, down 18). We concluded that U inhibited the expression of genes involved in the photosynthetic metabolic pathway, which caused the decrease of photosynthetic rate. Meanwhile, U inhibited the expression of the electron transport chain genes in the mitochondrial oxidative phosphorylation pathway, which leads to the abnormal energy supply of cells and the inhibition of root respiration rate.

Assessment of cyto- and genotoxic effects of Cesium-133 in Vicia faba using single-cell gel electrophoresis and random amplified polymorphic DNA assays.

The aim of this study was to evaluate the ecotoxic effect of high concentration cesium (Cs) exposure on plant root growth and its toxicological mechanism. The radicle of broad bean (Vicia faba) was selected as experimental material. The cytotoxic and genotoxic effects of plants exposed to different Cs levels (0.19-1.5 mM) for 48 h were evaluated using scanning electron microscopy (SEM), X-ray fluorescence (XRF) analysis, single-cell gel electrophoresis (SCGE) and random amplified polymorphic DNA (RAPD) assays. The results showed that radicle elongation decreased clearly after 48 h of exposure treatment with different concentrations of Cs solution. The root cell structure was obviously damaged in the Cs treatment groups (0.19-1.5 mM). At a Cs concentration of 1.5 mM, the percentages of viable non-apoptotic cells, viable apoptotic cells, non-viable apoptotic cells, and non-viable cells were 40.09%, 20.67%, 28.73%, and 10.52%, respectively. SCGE showed DNA damage in radicle cells 48 h after Cs exposure. Compared with the control group, the percentage of tail DNA in Cs exposed group (0.38-1.5 mM) increased by 0.56-1.12 times (P < 0.05). RAPD results showed that the genomic stability of V. faba radicles decreased by 4.44%-15.56%. This study confirmed that high concentration Cs exposure had cytotoxicity and genotoxicity effects on plants.

Apatinib is effective as third-line and more treatment of advanced metastatic non-small-cell lung cancer: A retrospective analysis in a real-world setting.

No standard methods are recommended for patients with advanced metastatic non-small-cell lung cancer (NSCLC) experiencing progression after 2 or more lines treatment now. The aim of this retrospective study was to assess the efficacy and safety of apatinib in metastatic NSCLC patients after second-line or more treatments failure in a real-world setting.A total of 52 advanced NSCLC patients who experienced progression after second-line and more treatments and received apatinib from March 2016 to February 2018 were retrospectively reviewed. Patients were treated with oral apatinib 500 mg QD (take the medicine once a day), every 4 weeks for a cycle. Responding and stable patients continued the treatment until progression or intolerable toxicity. The overall survival (OS), progression-free survival (PFS), objective remission rate (ORR) and disease control rate (DCR), and side effects of the drug were collected and reviewed.The ORR and the DCR were 6.9% and 67.4%. The median PFS and median OS of all patients were 3.8 months and 5.8 months, respectively. The Eastern Cooperative Oncology Group score was the independent influencing factor of PFS and OS for the advanced NSCLC patients who were treated with apatinib after second-line and above standard regimens (PFS: hazard ratio [HR] = 4.446, 95% confidence interval [CI]: 1.185-16.678, P = .027 and OS: HR = 8.149, 95% CI: 1.173-56.596, P = .034). The most common adverse events apatinib-related included hypertension (19.2%), hand-foot syndrome (11.5%), and mucous membrane reaction (17.3%). And treatment-related grade 3/4 toxicities were low.Apatinib showed favorable efficacy and safety and could be a treatment option in patients with advanced NSCLC experiencing progression after second-line and more treatment.

[Process optimization for extraction and purification of polysaccharides from Cistanche deserticola].

In this study, taking Cistanche deserticola in Xinjiang as the experimental material, the optimal process for extracting polysaccharides from C. deserticola with water extraction was studied by using single factor and orthogonal experiment. Its effects on protein removal and polysaccharides retaining were investigated by using Sevag, enzymatic method or combination of these two methods, so as to determine the optimal method for protein removal from polysaccharides of C. deserticola; the decolorization and purification methods such as macroporous resin of AB-8 and activated Carbon were used to determine the optimal process. The results showed that the extraction rate of polysaccharides from C. deserticola was 18.40% during the optimal process of the water extraction as follows: extraction temperature 75 ℃, extraction time 165 min and solid-liquid ratio 1∶55. The protein removal rate can reach 31.40% and polysaccharide retention rate can reach 96.00% under the optimal protein removal process: temperature 50 ℃, time 2 h, and papain dosage 0.2%. The decolorization rate of activated Carbon and macroporous resin called AB-8 was 80.37% and 86.43%, and the recovery rate of polysaccharides was 77.05% and 91.93%, respectively, suggesting that macroporous resin was more suitable for decoloration. Macroporous resin named AB-8 increased the purity of the polysaccharide crude extract from 67.70% to 84.80% under the following conditions: concentration of the sample 4 g·L~(-1), concentration of the eluent 60% ethanol, and the flow rate 1 mL·min~(-1), showing significant purification effect.

Analysis of differential gene expression by RNA-seq data in ABCG1 knockout mice.

AIMS: The previous studies on ABCG1 using genetically modified mice showed inconsistent results on atherosclerosis. The aim of this study was to determine whether accurate target knockout of ABCG1 would result in transcriptional changes of other atherosclerosis-related genes. METHODS: ABCG1 knockout mouse model was obtained by precise gene targeting without affecting non-target DNA sequences in C57BL/6 background. The wildtype C57BL/6 mice were regarded as control group. 12-week-old male mice were used in current study. We performed whole transcriptome analysis on the peripheral blood mononuclear cells obtained from ABCG1 knockout mice (n = 3) and their wildtype controls (n = 3) by RNA-seq. RESULTS: Compared with wildtype group, 605 genes were modified at the time of ABCG1 knockout and expressed differentially in knockout group, including 306 up-regulated genes and 299 down-regulated genes. 54 genes were associated with metabolism regulation, of which 13 were related to lipid metabolism. We also found some other modified genes in knockout mice involved in cell adhesion, leukocyte transendothelial migration and apoptosis, which might also play roles in the process of atherosclerosis. 7 significantly enriched GO terms and 19 significantly enriched KEGG pathways were identified, involving fatty acid biosynthesis, immune response and intracellular signal transduction. CONCLUSIONS: ABCG1 knockout mice exhibited an altered expression of multiple genes related to many aspects of atherosclerosis, which might affect the further studies to insight into the effect of ABCG1 on atherosclerosis with this animal model.

Pathological significance and regulatory mechanism of lymphotoxin ß receptor overexpression in T cells of patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a typical autoimmune disease. Lymphotoxin ß receptor (LTßR) signaling plays an important role in autoimmune inflammations. LTßR-Ig fusion protein, LTßR blocking agent, has been used to treat SLE, while its mechanism remains to be fully elucidated. In this study, to investigate the expression of LTßR in the T cells of SLE patients and its roles in the pathogenesis of SLE, we isolated the peripheral blood T cells of SLE patients and normal controls to detect expression of LTßR by flow cytometry and RNA assay. T cells were also stimulated with LIGHT, a ligand of LTßR, and then detected for their LTßR expressions and apoptosis by flow cytometry. Also, their expressions of inflammatory factors and receptors were determined by RNA assay. The results showed that LTßR positive cells were 22.75%±6.98% in CD3+ cells of SLE patients, while there were almost no LTßR positive cells in CD3+ cells of normal persons. Moreover, LTßR expression was remarkably higher in CD3, CD4 and CD8 positive T cells of active SLE patients than non/low active patients (all P<0.05), and positively correlated with increased Ig level, decreased complement level and renal damage. Moreover, the stimulation of SLE T cells with LIGHT promoted higher expression of LTßR, IL-23R and IL-17A, and apoptosis of T cells. In conclusion, we demonstrated a high expression of LTßR in the T cells of SLE patients which may be associated with pathogenesis of SLE.

Lactobacillus paracasei modulates LPS-induced inflammatory cytokine release by monocyte-macrophages via the up-regulation of negative regulators of NF-kappaB signaling in a TLR2-dependent manner.

The application of the probiotic lactobacillus is suggested in the treatment of some inflammatory diseases of intestines due to its potential ability to attenuate inflammation. However, the mechanism is not completely understood. In PBMCs, Lactobacillus paracasei (L. Paracasei) down-regulated the LPS-induced production of TNF-α and IL-6. Using a macrophage-like differentiated THP-1 cell line induced by PMA, we investigated the effect of L. paracasei on the production of pro-inflammatory cytokines by monocyte-macrophages. Treatment of the differentiated THP-1 cells with L. paracasei either concurrently with or before LPS challenge attenuated the LPS-induced secretion of TNF-α and IL-1ß. This effect was due to a decrease in IκB phosphorylation and NF-κB nuclear translocation. Furthermore, treatment of the differentiated THP-1 cells with L. paracasei induced the expression of negative regulators of the NF-κB signaling pathway, including the deubiquitinating enzyme A20, suppressor of cytokine signaling (SOCS) 1, SOCS3, and IL-1 receptor-associated kinase (IRAK) 3. Pretreatment with an IRAK4 inhibitor suppressed the L. paracasei-induced expression of these negative regulators and further increased the LPS-mediated expressions of TNF-α and IL-1ß. Moreover, treatment with an antibody against Toll-like receptor (TLR) 2 reversed the effect of L. paracasei on inducing negative regulators and inhibiting TNF-α and IL-1ß productions. Our findings suggest that L. paracasei inhibits the production of pro-inflammatory cytokines by monocyte-macrophages via the induction of negative regulators of the NF-κB signaling pathway in a TLR2-IRAK4-dependent manner.

A new ent-kaurane diterpene from Euphorbia stracheyi Boiss.

The chemical investigation of whole plants Euphorbia stracheyi Boiss from China led to the isolation of one new ent-kaurane diterpene, ent-Kaurane-16ß,17,19-triol-3-one (1), along with three known ent-kaurane diterpenoids (2-4) as ent-Kaurane-3α,16ß,17-triol (2)，ent-16S,17-dihydroxy-kaurane-3-one (3) and ent-3S,16S,17-trihydroxy-kaurane-2-one (4). Their structures were elucidated by extensive spectroscopic analyses including 1D, 2D NMR, HR-ESI-MS, and by comparison with the literature. Compound 2 was a new natural product and firstly isolated from nature, while compounds (3-4) were isolated from E. stracheyi for the first time. All isolated compounds (1-4) were evaluated for their cytotoxic activities against five human cancer cell lines (including A-549, SMMC-7721, HL-60, MCF-7 and SW-480).

[Induction of monocyte-derived dendritic cell differentiation by asthmatic serum in a transendothelial trafficking model].

OBJECTIVE: To explore the effect of asthmatic and healthy serum on differentiation and function of monocyte-derived dendritic cells (MDDC) in a transendothelial trafficking model. METHODS: The sera and peripheral blood mononuclear cells (PBMC) were separated from 12 asthmatic patients and 12 healthy volunteers, and monocytes were selected from PBMC using magnetic beads. The trypsin-digested human umbilical vein endothelial cells (HUVEC) at passage 2 from 5 healthy lying-in women were used to construct the transendothelial trafficking model under asthmatic or healthy serum, wherein MDDC were identified by silver nitrate staining and scanning electron microscopy. Nuclear factor κB (NF-κB) activity was determined by electrophoretic mobility shift assay. Flow cytometry, ELISA and mixed leukocyte reaction were relevantly utilized to detect the phenotype, cytokine and T cell proliferation. RESULTS: (1) Monocytes traversed through HUVEC monolayer after 2 h, and reverse-transmigrated to develop into DC 48 h later. (2) The healthy serum stimulated monocytes into immature MDDC with lower CD(14) [(20 ± 5)%] (F = 49.01, P < 0.05), and higher HLA-DR, CD(80), CD(86) and CD(83) [(43 ± 4)%, (17.9 ± 3.5)%, (43 ± 11)% and (6.7 ± 1.8)%, respectively] (F = 10.35 - 40.17, all P < 0.05) than monocytes did before transmigration at 0 h [CD(14) (81 ± 6)%, HLA-DR (24 ± 5)%, CD(80) (2.8 ± 2.0)%, CD(86) (14 ± 4)% and CD(83) (0.9 ± 0.8)%, respectively]. (3) The asthmatic serum stimulated monocytes into mature MDDC, characteristic of dendrites, with similar HLA-DR and CD(86) [(55 ± 6)% and (59 ± 12)%] (F = 15.29 and 35.97, all P > 0.05), higher CD(80) and CD(83) [(49.7 ± 10.2)% and (30.2 ± 6.8)%] (F = 4.01 and 20.68, all P < 0.05), accompanied by increased levels of NF-κB activity, IL-12 p70 and T cell proliferation [(100 ± 11)%, (568 ± 43) ng/L and (2033 ± 198) cpm, respectively] (F = 49.23 - 350.84, all P < 0.05) relative to the healthy serum-stimulated immature MDDC [(12 ± 3)%, (220 ± 35) ng/L and (952 ± 64) cpm, respectively]. CONCLUSION: The asthmatic serum induces mature MDDC in association with NF-κB overactivation in the transendothelial trafficking model, which provides a promising experimental platform for both investigation of immunological mechanisms in asthma and screening of novel anti-asthma drugs in vitro.

4-Hy-droxy-N'-[1-(2-hy-droxy-phen-yl)ethyl-idene]benzohydrazide.

In the title compound, C(15)H(14)N(2)O(3), there is an intra-molecular O-H⋯N hydrogen bond and the dihedral angle between the two aromatic rings is 13.9 (3)°. In the crystal structure, mol-ecules are stabilized by inter-molecular O-H⋯O and N-H⋯O hydrogen bonds.

Bis[2-(cyclo-pentyl-imino-meth-yl)-5-meth-oxy-phenolato]copper(II).

The title compound, [Cu(C(13)H(16)NO(2))(2)], is a mononuclear copper(II) complex derived from the Schiff base ligand 2-(cyclo-pentyl-imino-meth-yl)-5-meth-oxy-phenol and copper acetate. The Cu(II) atom is four-coordinated by the phenolate O atoms and imine N atoms from two Schiff base ligands, in a highly distorted square-planar geometry. The O- and N-donor atoms are mutually trans and the dihedral angle between the two benzene rings is 55.8 (3)°.

Bis{1-[3-(diethyl-ammonio)-propyl-imino-meth-yl]naphthalen-2-olato}nickel(II) dinitrate.

The asymmetric unit of the title compound, [Ni(C(18)H(24)N(2)O)(2)](NO(3))(2), consists of one half of the centrosymmetric nickel(II) complex cation and a nitrate anion. The Ni(II) atom, lying on an inversion center, is four-coordinated by the phenolate O atoms and imine N atoms of two Schiff base ligands, forming a square-planar geometry. The O- and N-donor atoms are mutually trans. In the crystal structure, the nitrate anions are linked to the complex cations by inter-molecular N-H⋯O hydrogen bonds.

Targeted NF-kappaB inhibition of asthmatic serum-mediated human monocyte-derived dendritic cell differentiation in a transendothelial trafficking model.

Transendothelial trafficking model mimics in vivo differentiation of monocytes into dendritic cells (DC). The serum from patients with systemic lupus erythematosus promotes the differentiation of monocytes into mature DC. We have shown that selective inhibition of NF-kappaB by adenoviral gene transfer of a novel mutated IkappaBalpha (AdIkappaBalphaM) in DC contributes to T cell tolerance. Here we demonstrated for the first time that asthmatic serum facilitated human monocyte-derived DC (MDDC) maturation associated with increased NF-kappaB activation in this model. Furthermore, selective blockade of NF-kappaB by AdIkappaBalphaM in MDDC led to increased apoptosis, and decreased levels of CD80, CD83, CD86, and IL-12 p70 but not IL-10 in asthmatic serum-stimulated MDDC, accompanied by reduced proliferation of T cells. These results suggest that AdIkappaBalphaM-transferred MDDC are at a more immature stage which is beneficial to augment the immune tolerance in asthma.

Adenovirus-mediated suicide gene therapy under the control of Cox-2 promoter for colorectal cancer.

Colorectal cancer is a most frequent type of gastrointestinal tract cancers. The prognosis of patients with colorectal cancer remains poor despite intensive interventions. Tumor specific promoter-directed gene therapy and adenoviral technology can be promising strategies for such advanced disease. This study was conducted to explore the possible therapeutic approach of Cox-2 promoter-directed suicide gene therapy with herpes simplex virus thymidine kinase (HSV-tk) in combination with adenoviral technology for advanced colorectal cancer. Firstly, the activity of Cox-2 promoter was assessed by dual luciferase and enhanced green fluorescent protein reporter gene assays in colorectal cancer cell lines and normal human intestinal epithelial cell line. Then, the expression of coxsackievirus and adenovirus receptor (CAR) was detected in colorectal cancer cell lines. The Cox-2 promoter-directed HSV-tk/ganciclovir (GCV) system mediated by adenovirus (Ad-Cp-TK) was developed (Ad-CMVp-TK, Ad-null and no Ad as controls). In vitro cytoxicity, colony formation and apoptosis assays were performed using Ad-Cp-TK. An animal study was carried out in which BALB/C nude mice bearing tumors were treated with Ad-Cp-TK and GCV treatments. Results showed that Cox-2 promoter possessed high transcriptional activity in a tumor-specific manner. All colorectal cancer cells were detected CAR-positive. In vitro cytotoxic and colony formation assays showed that colorectal cancer cells infected with Ad-Cp-TK became more sensitive to GCV but the sensitivity of normal cells infected with Ad-Cp-TK to GCV were not altered. Moreover, the Ad-Cp-TK system combined with GCV treatment could significantly induce apoptosis of colorectal cancer cells but not normal intestinal epithelial cells. Furthermore, this system also significantly inhibited the growth of subcutaneous tumors and prolonged survival of mice. Thus, adenovirus primary receptor was positive in colorectal cancer cells and adenovirus-mediated suicide gene therapy under the control of Cox-2 promoter could provide a promising treatment modality for advanced colorectal cancer with tumor specificity.

N'-(5-Bromo-2-hydr-oxy-3-methoxy-benzyl-idene)-4-hydr-oxy-3-methoxy-benzohydrazide dihydrate.

In the title compound, C(16)H(15)BrN(2)O(5)·2H(2)O, the dihedral angle between the two aromatic rings is 2.9 (2)° and an intra-molecular O-H⋯N hydrogen bond is observed. One of the water mol-ecule is disordered over two positions, with occupancies of 0.83 (3) and 0.17 (3). In the crystal structure, mol-ecules are linked into a three-dimensional network by inter-molecular O-H⋯O, O-H⋯(O,O), O-H⋯N and N-H⋯O hydrogen bonds. π-π inter-actions involving Br-substituted benzene rings, with a centroid-centroid distance of 3.552 (3) Šare also observed.