Occurrence, spatial distribution and risk assessment of organophosphate esters in surface water from the lower Yangtze River Basin.

Organophosphate esters (OPEs) are extensively used as flame retardants and plasticizers in China; however, their potential carcinogenicity causes great concern. To date, their environmental distribution in water samples from the lower Yangtze River Basin still remains uncharacterized. This study systematically investigated the occurrence and spatial distribution of 13 OPEs, as well as their associated potential risks, in water samples from the lower Yangtze River and its 88 major inflowing rivers. The total OPE (ΣOPEs) concentrations ranged from 55.6 to 5071 ng/L, with a median of 144 ng/L. Among them, halogenated OPEs were the dominant group with an average of 61.6%, and tris(1-chloro-2-propyl) phosphate (12.6-450 ng/L, median: 53.38 ng/L) and tris(2-choroethyl) phosphate (11.0-1202 ng/L, median: 36.4 ng/L) were the most abundant OPEs. Significantly different concentrations were found with spatial variations (p < 0.01), and were higher in southern cities than in northern cities of the lower Yangtze River Basin. Principal component analysis with multiple linear regression and Spearman correlations showed that the main sources were likely emission of vehicular and marine traffic. Ecological risk analysis showed that the risk quotient (RQ) values of samples remained below 1, but the percentage of 0.1 < RQ ≤ 1 was 26.9%, indicating a medium risk of OPEs in water samples. Moreover, ethylhexyl diphenyl phosphate predominantly contributed to the ecological risk, accounting for >89.2% of the total ecological risk of ΣOPEs. However, the total non-carcinogenic and carcinogenic risks of ΣOPEs were negligible at the detected concentrations, even in a high exposure scenario. The risks from major inflowing rivers of the lower Yangtze River were almost one order of magnitude higher than those of the mainstream lower Yangtze River.

Synthesis, biological evaluation and molecular docking of benzimidazole grafted benzsulfamide-containing pyrazole ring derivatives as novel tubulin polymerization inhibitors.

Tubulin-targeting drugs have increasingly become the focus of anticancer drugs research. Twenty-five novel benzimidazole grafted benzsulfamide-containing pyrazole ring derivatives were synthesized and evaluated for bioactivity as potential tubulin polymerization inhibitors. Among them, compound 30 showed the most excellent inhibition against tubulin assembly (IC50 = 1.52 µM) and in vitro growth inhibitory activity against a panel of four human cancer cell lines (IC50 = 0.15, 0.21, 0.33 and 0.17 µM, respectively for A549, Hela, HepG2 and MCF-7). It could also validly induce A549 cell apoptosis, cause cell cycle arrest in G2/M phase and disrupt the cellular microtubule network. These results, along with molecular docking data, provided an important basis for further optimization of compound 30 as a potential anticancer agent.

MicroRNA-4458 suppresses the proliferation of human lung cancer cells in vitro by directly targeting Lin28B.

Previous studies have shown that the expression of microRNA-4458 (miR-4458) is dysregulated in hepatocellular carcinoma and colon cancer. In this study, we investigated the direct target of miR-4458 and its biological functions in human lung cancer cells. By using the database TargetScan, we identified Lin28B, an oncogene, as a direct target gene of miR-4458. In dual-luciferase reporter assay, we found that miR-4458 mimics dose-dependently inhibited the luciferase activity of the wild-type 3'UTR of Lin28B in human lung cancer A549 and NCI-H1299 cell lines without affecting its mutant forms, whereas anti-miR-4458, an inhibitor of miR-4458, dose-dependently promoted the luciferase activity of the wild-type 3'UTR of Lin28B in A549 and NCI-H1299 cell lines without affecting its mutant forms. Overexpression of miR-4458 significantly decreased the protein levels of Lin28B in the cells, and inhibited the cell growth and colony formation. Conversely, knockdown of miR-4458 with anti-miR-4458 significantly increased the protein levels of Lin28B, and promoted the cell proliferation, which could be reverted by knockdown of Lin28B expression. In addition, we detected the expression of Lin28B using RT-PCR in 40 human lung cancer tissues and matched peritumoral tissues, and found that Lin28B was overexpressed in lung cancer tissues and negatively correlated with miR-4458 expression (r=-0.694, P<0.05). We conclude that miR-4458 is a tumor suppressor, and Lin28B is the direct target of miR-4458. These results suggest the modulation of miR-4458/Lin28B expression offers a potential therapeutic strategy for lung cancer.

Cell cycle protein Bora serves as a novel poor prognostic factor in multiple adenocarcinomas.

Cell cycle protein Bora has been identified to integrate the functions of three major mitotic kinases: Cyclin-dependent kinase-1, Polo-like kinase-1, and Aurora A kinase. Overexpression of Bora disrupts spindle assembly and causes genomic instability. However, the clinical relevance of Bora in cancer remains unclear. In this study, we examined the expression of Bora and its association with clinical characteristics in breast (n = 538), lung (n = 144) and gastric (n = 77) adenocarcinomas. We found that Bora was overexpressed in primary breast cancer tissues compared to paired non-cancerous tissues. Bora overexpression was observed at a higher proportion in triple-negative breast cancer (TNBC, 77.63%) compared with non-TNBC subtypes (42.76%, P < 0.0001). Kaplan-Meier survival analysis indicated that Bora overexpression was associated with unfavourable overall survival (OS, P < 0.0001) and disease-free survival (DFS, P = 0.007) in breast cancer. In addition, Bora subclassified patients with distinct clinical outcomes in both stages (II/III) and subtypes (HR+, HER2+) of breast cancer. Consistently, Bora was associated with adverse prognosis in lung (P = 0.005 for OS and DFS P = 0.001 for DFS) and gastric adenocarcinomas (P < 0.0001 for OS, and P < 0.0001 for DFS). Moreover, Bora was positively correlated with proliferation index Ki67 in breast and gastric cancer (P < 0.001, P = 0.005, respectively). Multivariate analyses further revealed that Bora was an independent prognostic parameter for OS and DFS in all three types of adenocarcinomas. In conclusion, our findings demonstrated that Bora was overexpressed and served as an independent biomarker for poor prognosis in multiple adenocarcinomas.

Synthesis, molecular docking and biological evaluation of 1-phenylsulphonyl-2-(1-methylindol-3-yl)-benzimidazole derivatives as novel potential tubulin assembling inhibitors.

A series of new 1-phenylsulphonyl-2-(1-methylindol-3-yl)-benzimidazole derivatives were designed, synthesized and evaluated as potential inhibitors of tubulin polymerization and anthropic cancer cell lines. Among them, compound 33 displayed the most potent tubulin polymerization inhibitory activity in vitro (IC50  = 1.41 µM) and strong antiproliferative activities against A549, Hela, HepG2 and MCF-7 cell lines in vitro with GI50 value of 1.6, 2.7, 2.9 and 4.3 µM, respectively, comparable with the positive control colchicine (GI50 value of 4.1, 7.2, 9.5 and 14.5 µM, respectively) and CA-4 (GI50 value of 2.2, 4.3, 6.4 and 11.4 µM, respectively). Simultaneously, we evaluated that compound 33 could effectively induce apoptosis of A549 associated with G2/M phase cell cycle arrest. Immunofluorescence microscopy also clearly indicated compound 33 a potent antimicrotubule agent. Docking simulation showed that compound 33 could bind tightly with the colchicine-binding site and act as a tubulin inhibitor. Three-dimensional-QSAR model was also built to provide more pharmacophore understanding that could be used to design new agents with more potent tubulin assembling inhibitory activity in the future.

Fatty acid binding protein (FABP) inhibitors: a patent review (2012-2015).

INTRODUCTION: Obesity, diabetes, atherosclerosis, hypertension, dyslipidemia, and metabolic syndrome are synergistically operating diseases that endanger human health. Many studies provide evidence for excessive free fatty acid (FFA) as the pathogenic factor of these diseases. Fatty acid binding proteins (FABPs), which are responsible for the transfer of FFA to different cell compartments, play a key role in cellular functions. Therefore, the discovery and application of FABP inhibitors may be a potential strategy to control obesity, atherosclerosis, diabetes, and metabolic syndrome diseases in humans. AREAS COVERED: This review focuses on the applications of FABP inhibitors in the prevention and treatment of obesity, atherosclerosis, diabetes, and metabolic syndromes. A comprehensive description of patents related to FABP inhibitors from 2012 to 2015 is included. EXPERT OPINION: FABP has proven to be a promising target for the treatment of obesity, atherosclerosis, diabetes, and metabolic syndrome, and there have been major advances in the development of FABP inhibitors for this purpose. However, there continue to be new claims for novel FABP inhibitors with higher activity and specificity. Moreover, FABP inhibitors are potential drugs for other applications involving anti-cancer and neurological regulatory functions.

A Brief Review of Bioactive Metabolites Derived from Deep-Sea Fungi.

Deep-sea fungi, the fungi that inhabit the sea and the sediment at depths of over 1000 m below the surface, have become an important source of industrial, agricultural, and nutraceutical compounds based on their diversities in both structure and function. Since the first study of deep-sea fungi in the Atlantic Ocean at a depth of 4450 m was conducted approximately 50 years ago, hundreds of isolates of deep-sea fungi have been reported based on culture-dependent methods. To date more than 180 bioactive secondary metabolites derived from deep-sea fungi have been documented in the literature. These include compounds with anticancer, antimicrobial, antifungal, antiprotozoal, and antiviral activities. In this review, we summarize the structures and bioactivities of these metabolites to provide help for novel drug development.

Synthesis, biological evaluation, and molecular docking studies of novel 1-benzene acyl-2-(1-methylindol-3-yl)-benzimidazole derivatives as potential tubulin polymerization inhibitors.

A series of 1-benzene acyl-2-(1-methylindol-3-yl)-benzimidazole derivatives were designed, synthesized and evaluated as potential tubulin polymerization inhibitors and for the cytotoxicity against anthropic cancer cell lines. Among the novel compounds, compound 11f was demonstrated the most potent tubulin polymerization inhibitory activity (IC50 = 1.5 µM) and antiproliferative activity against A549, HepG2 and MCF-7 (GI50 = 2.4, 3.8 and 5.1 µM, respectively), which was compared with the positive control colchicine and CA-4. We also evaluated that compound 11f could effectively induce apoptosis of A549 associated with G2/M phase cell cycle arrest. Docking simulation and 3D-QSAR model in these studies provided more information that could be applied to design new molecules with more potent tubulin inhibitory activity.

[Effects of cetylpyridinium chloride buccal tablets on halitosis induced by oral conditions].

OBJECTIVE: To investigate the effect of cetylpyridinium chloride buccal tablets on halitosis induced by oral conditions. METHODS: With Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum as the testing bacteria, the minimal inhibitory concentration (MIC) of cetylpyridinium chloride buccal tablets was determined using minute amount serial dilution test. The production of volatile sulfur compounds (VSCs) was measured using sulfide detector halimeter in the anaerobic bacteria culture at 4 and 8 h after addition of the tablets. The effect of the tablets in suppressing odor production by mouth-borne halitosis bacteria was assessed using cysteine challenge test in healthy volunteers, and the effectiveness was evaluated by measuring the reduction in VSCs production and the duration of the effect. RESULTS: Cetylpyridinium chloride buccal tablets inhibited the growth of all the 3 bacteria. The tablets obviously inhibited VSCs production by the 3 bacteria with a effect similar to chlorhexidine. Compared with distilled water gargle, the buccal tablets significantly reduced cysteine-induced VSCs production level in the healthy volunteers (P<0.05), and the effect lasted for 230 min. CONCLUSION: Cetylpyridinium chloride tablets can obviously suppress bacteria responsible for oral halitosis and produce good effects in the treatment of halitosis induced by oral conditions.

Hepatocellular carcinoma that arose from primary Sjögren's syndrome.

Hepatocellular carcinoma (HCC) typically originates from HBV or HCV associated liver cirrhosis. Primary Sjögren's syndrome (pSS) is a kind of autoimmune disease. A sixty-two year old female patient with mild liver damage was diagnosed with pSS after excluding viral, alcoholic and drug-induced hepatitis according to serum immunological detection and liver biopsy. But when she was hospitalized for a second time two years later, a CT scan revealed liver neoplasm. Surgery confirmed HCC and liver cirrhosis by pathology. The elevated level of AFP recovered to normal after tumorectomy. In conclusion, HCC might be a candidate outcome in patients with pSS; it is the doctors' responsibility to keep this kind of patient under surveillance.

Modestobacter roseus sp. nov., an endophytic actinomycete isolated from the coastal halophyte Salicornia europaea Linn., and emended description of the genus Modestobacter.

A novel actinomycete, designated strain KLBMP 1279(T), was isolated from surface-sterilized roots of a coastal halophyte, Salicornia europaea Linn., collected from Jiangsu Province, in the east of China. The taxonomic status of this organism was established using a polyphasic approach. 16S rRNA gene sequence analysis indicated that strain KLBMP 1279(T) was closely related to Modestobacter marinus 42H12-1(T) (99.5% 16S rRNA gene sequence similarity), Modestobacter versicolor CP153-2(T) (98.4%) and Modestobacter multiseptatus AA-826(T) (97.5%). Chemotaxonomic characteristics were consistent with its assignment to the genus Modestobacter in that the isolate had meso-diaminopimelic acid as the diagnostic diamino acid in the cell wall, MK-9(H4) as major menaquinone and a polar lipid profile containing diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannosides, two unknown aminophospholipids and an unknown phospholipid. The predominant fatty acids were iso-C16:0, iso-C15:0 and C17:1ω8c. The DNA G+C content was 71.7 mol%. However, DNA-DNA hybridization assays as well as physiological and biochemical analyses differentiated strain KLBMP 1279(T) from its closest phylogenetic relatives. On the basis of phenotypic, chemotaxonomic and phylogenetic evidence, the isolate KLBMP 1279(T) represents a novel species of the genus Modestobacter, for which the name Modestobacter roseus sp. nov. is proposed; the type strain is KLBMP 1279(T) (=KCTC 19887(T)=NBRC 108673(T)=DSM 45764(T)). An emended description of the genus Modestobacter is also proposed.

[Influence of surface modification of titanium on OPG/RANKL mRNA expression in MG-63 human osteoblast-like cells].

OBJECTIVE: To investigate the influence of surface modification of titanium on OPG/RANKL mRNA expression in human osteoblast-like cells. METHODS: MG-63 osteoblast-like cells were seeded on the titanium plates with surface polishing and with surface modification by sandblasting plus acid-base treatment, with the cells on glass slides as the control. On days 2, 4, 6, and 8 following cell seeding, the cells were harvested for examination of OPG/RANKL mRNA expression using RT-PCR and real-time PCR. RESULTS: The expression of OPG/RANKL mRNA was sensitive to the surface microphotography. Compared with the other groups, the cells on the titanium plates with sandblasting plus acid-base treatment, which resulted in a porous micro-structure and high roughness, showed significantly up-regulated expression of OPG mRNA. OPG mRNA expression also showed a time-dependent up-regulation, and was the highest on day 8. The expression of the RANKL mRNA in cells on both of the titanium plates was higher than that in the control cells. The peak level of RANKL mRNA expression occurred on day 6 followed by a gradual decrease. CONCLUSION: A rough and porous surface of the culture plates and prolonged culture time can synergistically up-regulate the ratio of OPG/RANKL mRNA.

Synthesis, molecular modeling and biological evaluation of PSB as targeted antibiotics.

We described here the design, synthesis, molecular modeling, and biological evaluation of a series of peptide and Schiff bases (PSB) small molecules, inhibitors of Escherichia coli beta-Ketoacyl-acyl carrier protein synthase III (ecKAS III). The initial lead compound was reported by us previously, we continued to carry out structure-activity relationship studies and optimize the lead structure to potent inhibitors in this research. The results demonstrated that both N-(2-(3,5-dichloro-2-hydroxybenzylideneamino)propyl)-2-hydroxybenzamide (1f) and 2-hydroxy-N-(2-(2-hydroxy-5-iodobenzylideneamino)propyl)-4-methylbenzamide (3e) posses good ecKAS III inhibitory activity and well binding affinities by bonding Gly152/Gly209 of ecKAS III and fit into the mouth of the substrate tunnel, and can be as potential antibiotics agent, displaying minimal inhibitory concentration values in the range 0.20-3.13microg/mL and 0.39-3.13microg/mL against various bacteria.

[Value of diffusion weighted imaging in diagnosis of nodular lesions of thyroid: a preliminary study].

OBJECTIVE: To investigate the value of magnetic resonance diffusion weighted imaging (DWI) in the differential diagnoses of malignant and benign thyroid lesions. METHODS: Using echo planner imaging sequence with b value of 0, 100, 200, 300 and 400 s/mm(2) respectively, DWI was performed in 60 patients of focal thyroid lesions. The diagnosis was confirmed by pathological examination (benign, n = 30; malignant, n = 30). Apparent diffusion coefficient (ADC) values were measured. The differences were analyzed between two groups. RESULTS: With b value of 0, 100, 200, 300 and 400 s/mm(2) respectively, there were statistical differences in ADC values between benign and malignant lesions. The ADC value of malignant lesions was smaller than that of benign lesions (P < 0.05). Among different b values, 400 s/mm(2) was the most optimal one to diagnose thyroid nodular lesions. DWI with a b value of 400 s/mm(2) had a proper signal-to-noise ratio (SNO). And ADC value could be measured correctly. With a b value of 400 s/mm(2) and ADC of 1.475 × 10(-3) mm(2)/s, receiver operating characteristic curve was plotted. In the diagnosis of malignant lesions, the sensitivity and specificity were 93.3% and 96.7% respectively. CONCLUSIONS: The ADC value of malignant thyroid nodular lesions is smaller than that of benign lesions. The values of DWI and ADC are important in the differential diagnoses of nodular thyroid lesions.

Tris[4-chloro-2-(2-furylmethyl-imino-meth-yl)phenolato-κO,N]iron(III).

The title complex, [Fe(C(12)H(9)ClNO(2))(3)], is a mononuclear Schiff base iron(III) compound. The Fe atom is six-coordinated by three phenolic O and three imine N atoms from three Schiff base ligands in an octa-hedral geometry.

[Stringent RNA polymerase of E. coli and its in vivo transcriptional activity].

Several spontaneous E. coli mutants with the similar phenotype as that in the condition of amino acid deficiency were obtained on the selective media. One of the mutants (LCH001) showing slow growth phenotype on LB agar plate and pink or white colonies on MacConkey agar plate was mapped at rpoC gene encoding the beta' subunit of RNA polymerase by phage P1 transduction and transformation assays and found to be a new site mutation from G to T at 3406bp in the rpoC gene, which resulted in the amino acid change from Glycine (GGT) to Cysteine (TGT). The effect of the mutation on transcriptional activity of both stringent and non-stringent controlled promoters in vivo was measured by determining the beta-galactolactase activity of the growing cells. Results showed that the transcriptional activity of the mutant LCH001 reduced greatly on the stringent promoter, but increased significantly on the non-stringent promoter. The beta-galactolactase activity of the mutant LCH001 transcribed on stringent promoter was 18% lower, but 5-fold higher on the non-stringent controlled promoter than that of the wild-type strain CLT5034. This finding may give insights into future studies of the structure-function relationship of RNA polymerase as well as its role in the stringent response of bacteria.