Induction of Antiphytopathogenic Metabolite and Squalene Production and Phytotoxin Elimination by Adjustment of the Mode of Fermentation in Cocultures of Phytopathogenic Nigrospora oryzae and Irpex lacteus.

The investigation of the metabolites from different cocultures of Nigrospora oryzae and Irpex lacteus in solid medium revealed two new squalenes (1 and 2); one new azaphilone (3); two new tremulane sesquiterpenes (4 and 5); and three known compounds, conocenol B (6), conocenol C (7), and 4-(4-dihydroxymethylphenoxy)benzaldehyde (8). The antagonistic relationship was examined by studying metabolite production. The production of compounds 6 and 8 by I. lacteus after the induction of coculture indicated significant selectivity for antifungal activity against phytopathogenic N. oryzae, with MICs of 16 µg/mL; compounds 6 and 8 also exhibited antifungal activities in vivo against Cerasus cerasoides infected by N. oryzae at concentrations of 100 µg/mL. New compounds 2 and 4 showed antifungal activities against Colletotrichum gloeosporioides, with MICs of 8 µg/mL, and compound 4 showed antifungal activity against Didymella glomerata with an MIC of 1 µg/mL. These results indicate that the mutually antagonistic relationship in the coculture of the phytopathogen and the endophyte can result in antibiotics that inhibit the phytopathogen and downregulate the production of phytotoxins by phytopathogenic N. oryzae. New compound 5 from I. lacteus showed weak activity against acetylcholinesterase (AChE), with an inhibition ratio of 16% at a concentration of 50 µM.

Fabrication of magnetically separable fluorescent terbium-based MOF nanospheres for highly selective trace-level detection of TNT.

In this work, we present novel kinds of Fe3O4@Tb-BTC magnetic metal-organic framework (MOF) nanospheres which possess both magnetic characteristics and fluorescent properties using a layer by layer assembly technique. The structure and morphology of the as-prepared Fe3O4@Tb-BTC were systematically characterized and it was applied in detection of nitroaromatic explosives, such as 2,4-dinitrotoluene (2,4-DNT), 2,6-dinitrotoluene (2,6-DNT), 2-nitrotoluene (2-NT), 4-nitrotoluene (4-NT), nitrobenzene (NB) and picric acid (PA). The results indicate that the fluorescence intensity of Fe3O4@Tb-BTC can be quenched by all analytes studied in the present work. Remarkably, the as-synthesized nanospheres exhibit high sensitivity for 2,4,6-trinitrotoluene (TNT) detection with Ksv value of (94 800 M(-1)). Besides, the magnetic nanospheres can be easily recycled, which makes it more convenient for reutilization and friendly to the environment. The results show that it has broad application prospects in the detection of nitroaromatic explosives.

[The protective effect of photochromic intraocular lens on visible light-induced lesion in cultured retinal pigment epithelium].

OBJECTIVE: To evaluate the protective effect of photochromic intraocular lens (IOL) on visible light-induced lesion in cultured retinal pigment epithelium (RPE). METHODS: It was a experimental study. A human retinal pigment epithelium cell line (ARPE-19) was used to study the protective role. Cells from the same passage were divided into the control, light exposure only, light exposure plus colorless IOL (FV-60A), light exposure plus photochromic IOL (BV-60A), light exposure plus yellow IOL (Acrysof Natural IOL) groups. The treatments were performed when the cells grew to 90% confluency. All cells were irradiated with visible light at an illumination intensity of 60 000-61 000 lux. After the treatments, we assessed 1: cells' viability by methyl thiazolyl tetrazolium (MTT) assay; 2: the extent of apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), observing changes in the ultrastructure by transmission electron microscopy (TEM), and performing Hoechst staining to measure the apoptosis index (AI); 3: examining vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) levels in the culture medium by enzyme linked immunosorbent assay (ELISA). RESULTS: Measurements of the cell viability of the five groups were (0.61 ± 0.01), (0.39 ± 0.01), (0.46 ± 0.01), (0.57 ± 0.01), and (0.58 ± 0.02), respectively. Apoptosis was significantly activated by visible light as observed in TUNEL staining and TEM. The AIs of the five groups were (0.99 ± 0.65)%, (9.28 ± 0.59)%, (6.54 ± 0.37)%, (4.69 ± 0.74)%, and (2.72 ± 0.67)%, respectively. The levels of VEGF in the five groups were (3931.64 ± 25.26) ng/L, (5459.38 ± 42.69) ng/L, (4800.55 ± 42.12) ng/L, (4561.21 ± 46.27) ng/L, and (4420.35 ± 28.66) ng/L, respectively. The levels of PEDF in the five groups were (182.85 ± 1.68) µg/L, (156.52 ± 0.64) µg/L, (155.57 ± 3.43) µg/L, (167.57 ± 2.88) µg/L, and (170.90 ± 2.99) µg/L, respectively. Comparing the photochromic IOL group with the yellow IOL group, there was no difference in cell viability (q = 0.94) and PEDF levels (q = 1.51) (P > 0.05), but there was a significant difference between the AI (q = 5.04) and VEGF levels (q = 6.78) (P < 0.05). Comparing the photochromic IOL group with the colorless IOL group, there were significant differences in cell viability (q = 18.92) , AI (q = 4.78) , VEGF (q = 11.52) and PEDF levels (q = 4.96) (P < 0.05). CONCLUSIONS: Photochromic IOL can abate the degree of acute photodamage of RPE. The protective efficiency was the highest when using the yellow Acrysof Natural IOL, followed by photochromic IOL and colorless IOL.

[Curcumin inhibits iron overload-induced hepatocytic apoptosis and nuclear factor-κB activity].

OBJECTIVE: Iron is an essential micronutrient for human beings but its overload induces various diseases of liver, the main body storage site for iron, such as liver fibrosis. Curcumin is a natural polyphenol derived from turmeric and has been used widely. Its pharmacological action has attracted great attention in recent years. The apoptosis of rat cultured hepatocytes was induced by FeNTA (ferric nitrilotriacetate)-induced Iron overload. The present study was to examine the effect of curcumin at low concentrations on FeNTA-induced apoptosis of hepatocytes and elucidate the underlying mechanisms. METHODS: After the incubation of hepatocytes with 100 µmol/L FeNTA in the presence or absence of 1 - 10 µmmol/L of curcumin, a series of analyses were performed, including the analyses of hepatocytic apoptosis, the expressions of proteins relating with the regulations of cell apoptosis, caspase-3 activity, the production of reactive oxygen species (ROS) and nuclear factor NF-κB activity. RESULTS: Curcumin reduced the FeNTA-induced hepatocytic apoptosis by 46.65% and significantly down-regulated the protein levels of Bcl-2 and Bcl-XL. In contrast, it had no effect on the protein levels of Bax and Bad. The curcumin treatment reduced FeNTA-caused production of ROS and caspase-3 activity by 45.01% and 59.71% respectively. And the NF-κB activity was also inhibited. CONCLUSION: Curcumin at low concentrations reduces iron overload-caused hepatocytic apoptosis and NF-κB activity, the key regulatory transcription factor for the inflammation-related gene expression in cultured hepatocyte.

Quetiapine N-oxide-fumaric acid (2/1).

THE TITLE COMPOUND (SYSTEMATIC NAME: 2-{2-[4-(dibenzo[b,f][1,4]thia-zepin-11-yl)piperazin-1-yl 1-oxide]eth-oxy}ethanol-fumaric acid (2/1)), C(21)H(25)N(3)O(3)S·0.5C(4)H(4)O(4), is one of the oxidation products of quetiapine hemifumaric acid. In the tricyclic fragment, the central thia-zepine ring displays a boat conformation and the benzene rings are inclined to each other at a dihedral angle of 72.0 (2)°. The piperazine ring adopts a chair conformation with its eth-oxy-ethanol side chain oriented equatorially. In addition to the main mol-ecule, the asymmetric unit contains one-half mol-ecule of fumaric acid, the complete mol-ecule being generated by inversion symmetry. In the crystal, O-H⋯O hydrogen bonds link the components into corrugated layers parallel to bc plane.

Marbofloxacin.

IN THE TITLE COMPOUND, [SYSTEMATIC NAME: 9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-piperazin-1-yl)-7-oxo-7H-pyrido[1,2,3-ij][1,2,4]benzoxadiazine-6-carb-oxy-lic acid], C(17)H(19)FN(4)O(4), the carbonyl and carboxyl groups are coplanar with the quinoline ring, making a dihedral angle of 2.39 (2)°. The piperazine ring adopts a chair conformation and the oxadiazinane ring displays an envelope conformation with the CH(2) group at the flap displaced by 0.650 (2) Šfrom the plane through the other five atoms. The mol-ecular structure exhibits an S(6) ring motif, owing to an intra-molecular O-H⋯O hydrogen bond. In the crystal, weak C-H⋯F hydrogen bonds link mol-ecules into layers parallel to the ab plane.

Endoscopic ultrasonography for the diagnosis and selecting treatment of esophageal leiomyoma.

BACKGROUND AND AIM: To investigate the clinical value of endoscopic ultrasonography (EUS) with miniature ultrasonic probes (MUP) for the diagnosis and treatment of esophageal leiomyoma. METHODS: A total of 229 patients with esophageal leiomyoma, diagnosed using EUS, with 12-MHz MUP and a double-cavity electronic endoscope, were enrolled. The clinical characteristics of the patients were analyzed, and those who had therapeutic indications received endoscopic resection or surgical excision. Postoperative histological diagnostic results were compared with the preoperative diagnosis of EUS. All patients, including those with or without endoscopic resection or surgical excision were periodically followed up with EUS. RESULTS: Of the 229 patients, 118 received endoscopic resection, and seven received surgical excision. Postoperative histology showed that 110 patients were completely consistent with the preoperative diagnosis of EUS, and the diagnostic accuracy of EUS was 88.6%. No treatment-related complications occurred among the patients who received endoscopic resection or surgical excision, and no recurrence was observed during the follow-up examinations. CONCLUSIONS: Esophageal leiomyoma is a benign tumor of the esophagus. EUS is a useful technique for the diagnosis of esophageal leiomyoma and for making treatment-related decisions.

Moxifloxacinium chloride monohydrate.

The title compound {systematic name: 7-[(1S,6S)-8-aza-2-azonia-bicyclo-[4.3.0]non-8-yl]-1-cyclo-propyl-6-fluoro-8-meth-oxy-4-oxo-1,4-dihydro-quinoline-3-carb-oxy-lic acid chloride monohydrate}, C(21)H(25)FN(3)O(4) (+)·Cl(-)·H(2)O, crystallizes with two moxi-floxa-cinium cations, two chloride ions and two uncoordinated water mol-ecules in the unit cell. The crystal structure has a pseudo-inversion center except for the chloride ions. In both moxi-floxa-cinium cations, the quinoline rings are approximately planar, the maximum atomic deviations being 0.107 (3) and 0.118 (3) Å. The piperidine rings adopt a chair conformation while the pyrrolidine rings display a half-chair conformation. In the crystal, the carboxyl groups, the protonated piperidyl groups, the uncoordinated water mol-ecule and chloride anions participate in O-H⋯O, O-H⋯Cl and N-H⋯Cl hydrogen bonding; weak inter-molecular C-H⋯O and C-H⋯Cl hydrogen bonding is also present in the crystal structure.

Eprosartan mesylate, an angiotensin II receptor antagonist.

The title compound, eprosartan mesylate {systematic name: 2-butyl-1-(4-carb-oxy-benz-yl)-5-[(E)-2-carb-oxy-3-(thio-phen-2-yl)prop-1-en-yl]-1H-imidazol-3-ium methane-sulfonate}, C(23)H(25)N(2)O(4)S(+)·CH(3)O(3)S(-), one of the angiotensin II-receptor antagonists, is effective in regulating hypertension, induced or exacerbated by angiotensin II, and in the treatment of congestive heart failure, renal failure and glaucoma. In the eprosartan residue, which appears in this crystal in the cationic imidazolium form, the benzene ring plane is almost orthogonal to that of the imidazole ring, making a dihedral angle of 87.89 (2)°. The thio-phene ring forms dihedral angles of 66.54 (2) and 67.12 (2)° with the benzene and imidazole rings, respectively. The imidazolium NH group and the H atom of the aromatic carboxyl group participate in hydrogen bonds with the the O atoms of the anion, thus forming centrosymmetric aggregates made up of two cations and two anions each. The second carboxyl group further links the above-mentioned aggregates through a conventional centrosymmetric hydrogen-bonding motif into infinite chains along [011].

Febuxostat methanol solvate.

In the title compound {systematic name: [2-(3-cyano-4-isobutyl-oxyphen-yl)-4-methyl-1,3-thia-zole-5-carb-oxy-lic acid (febuxostat) methanol monosolvate}, C(16)H(16)N(2)O(3)S·CH(4)O, the benzene and thia-zole rings in the febuxostat mol-ecule are twisted at 5.3 (1)°. In the crystal structure, inter-molecular O-H⋯O and O-H⋯N hydrogen bonds link the febuxostat and methanol mol-ecules into helical chains along the 2(1) screw axis.

Ultrasonographic characteristics of urolithiasis in children exposed to melamine-tainted powdered formula.

BACKGROUND: Since the outbreak of renal diseases among children who had consumed melamine-tainted powdered formula in 2008, urinary system ultrasound examination was carried out for these children at our hospital. This study aimed to investigate the ultrasonographic characteristics of urolithiasis caused by melamine-tainted powdered formula. METHODS: From September 12 to October 9, 2008, urinary system ultrasound examination for children after consumption of melamine-tainted powdered formula was carried out at the Children's Hospital of Zhejiang University, China. A total of 15,577 infants and children were subjected to the examination. A questionnaire with items including demographic characteristics, history of exposure and clinical symptoms were completed before examination. RESULTS: Among the 15,577 children, 7988 were boys and 7,589 girls with age ranging from 1 month to 15 years (mean age, 22 months). Urolithiasis was found in 562 patients with an identification rate of 3.6%. Urolithiasis was identified mainly in the children aged 36 months or younger (88.6%). Unilateral kidney calculi were found in 431 children and bilateral kidney calculi in 131 children. Eleven of these children also had ureteric calculi, 1 had bladder calculi, 2 had urethral calculi, and 2 had gallbladder calculi. Fifteen children had urinary tract obstruction. Ultrasonographic characteristics of these melamine calculi were different from the calcium oxalate calculi, i.e., the lesions were less echogenic, had a more "sandy" appearance and were less dense. The posterior portion of the calculi could be observed and was accompanied with a feeble or absent acoustic shadow. CONCLUSIONS: Melamine-induced calculi were ultrasonographically less echogenic, sand-like and discrete; the posterior portion of the calculi was accompanied with a feeble or absent acoustic shadow. It might be a new type of urolithiasis in children.

[Clinical research on angiogenesis in colorectal carcinoma and expression of CK20 mRNA in peripheral blood].

OBJECTIVE: To investigate the correlation between microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in tissues of colorectal carcinoma and the micrometastasis of tumor cells in these patients' peripheral blood. METHODS: The MVD and expression of VEGF were evaluated immunohistochemically while the micrometastasis of tumor cells in these patients' peripheral blood was detected by RT-PCR method. RESULTS: The average count of MVD in high and middle differentiation grade was 30.2 +/- 12.7, while in low differentiation grade 86.6 +/- 19.1. The expression of VEGF was positive in 26 patients (44.8%). The MVD and positive expression of VEGF were correlated to differentiations. stage and metastasis of colorectal carcinoma. CK(20) mRNA was found in peripheral blood of 32 patients (55.2%) and the positive rate was up to 60.4% 48 hours after operation, among which positive rate in the radical resection group was 47.7% and in the non-radical resection group 85.7%. 11 out of 21 patients positive in CK(20) mRNA turned to negative 7-14 d after radical resection, while 11 out of 12 patients remained positive at the same time after non-radical resection. The expression of CK(20) mRNA was correlated to the stage and metastasis of the cancer. The MVD and positive expression of VEGF were higher in patients with positive expression of CK(20) mRNA. CONCLUSIONS: The MVD and positive expression of VEGF were correlated to differentiation, stage and metastasis of colorectal carcinoma. The angiogenesis in tissues of colorectal carcinoma was closely related to the micrometastasis of tumor cells in these patients' peripheral blood. The detecting of CK(20)mRNA by RT-PCR may be a sensitive method for evaluating the micrometastasis colorectal carcinoma in peripheral blood and help in prognosis prediction, effect assessment and guidance of multipurpose therapy.

Stable antibody expression at therapeutic levels using the 2A peptide.

Therapeutic monoclonal antibodies (mAbs) are currently being developed for the treatment of cancer and other diseases. Despite clinical success, widespread application of mAb therapies may be limited by manufacturing capabilities. In this paper, we describe a mAb delivery system that allows continuous production of a full-length antibody at high-concentrations in vivo after gene transfer. The mAb is expressed from a single open reading frame by linking the heavy and light chains with a 2A self-processing peptide derived from the foot-and-mouth disease virus. Using this expression system, we generated a recombinant adeno-associated virus vector encoding the VEGFR2-neutralizing mAb DC101 (rAAV8-DC101). A single dose of rAAV8-DC101 resulted in long-term expression of >1,000 microg/ml of DC101 in mice, demonstrating significant anti-tumor efficacy. This report describes the first feasible gene therapy approach for stable delivery of mAbs at therapeutic levels, which may serve as an attractive alternative to direct injection of mAbs.

Enhanced cell attachment and osteoblastic activity by P-15 peptide-coated matrix in hydrogels.

The cells in bone grow on a composite matrix made up of mineral and organic (mainly type-I collagen) components. In this study, anorganic bone mineral (ABM) particles were coated with a cell-binding domain of type-I collagen (P-15 peptide) to mimic the bone matrix components and suspended in injectable hyaluronate (Hy) hydrogels. The ABM/P-15/Hy was compared to ABM/Hy-the same matrix without P-15 peptide. Osteoblast-like HOS cells migrated through the hydrogels around ABM/P-15 or ABM particles; however, more cells adhered to ABM/P-15/Hy particles, and the cells formed better surface coverage and had more stress fibers on ABM/P-15/Hy. HOS cells cultured on ABM/P-15/Hy had increased osteogenic gene expression for alkaline phosphatase and bone morphogenetic proteins, and deposited more mineralized matrix. Studies with two different hydrogels (carboxymethylcellulose and sodium alginate) showed similar enhanced cell attachment and mineralization. The studies suggest that the ABM/P-15 in hydrogels can be used as an injectable biomimetic matrix to facilitate bone repair.