Genome sequencing and transcriptome analyses provide insights into the origin and domestication of water caltrop (Trapa spp., Lythraceae).

Humans have domesticated diverse species from across the plant kingdom; however, our current understanding of plant domestication is largely founded on major cereal crops. Here, we examine the evolutionary processes and genetic basis underlying the domestication of water caltrop (Trapa spp., Lythraceae), a traditional, yet presently underutilized non-cereal crop that sustained early Chinese agriculturalists. We generated a chromosome-level genome assembly of tetraploid T. natans, and then divided the allotetraploid genome into two subgenomes. Based on resequencing data from 57 accessions, representing cultivated diploid T. natans, wild T. natans (2x and 4x) and diploid T. incisa, we showed that water caltrop was likely first domesticated in the Yangtze River Valley as early as 6300 yr BP, and experienced a second improvement c. 800 years ago. We also provided strong support for an allotetraploid origin of T. natans within the past 230 000-310 000 years. By integrating selective sweep and transcriptome profiling analyses, we identified a number of genes potentially selected and/or differentially expressed during domestication, some of which likely contributed not only to larger fruit sizes but also to a more vigorous root system, facilitating nutrient uptake, environmental stress response and underwater photosynthesis. Our results shed light on the evolutionary and domestication history of water caltrop, one of the earliest domesticated crops in China. This study has implications for genomic-assisted breeding of this presently underutilized aquatic plant, and improves our general understanding of plant domestication.

Calcitriol inhibits migration and invasion of renal cell carcinoma cells by suppressing Smad2/3-, STAT3- and ß-catenin-mediated epithelial-mesenchymal transition.

Low vitamin D status is associated with progression in patients with renal cell carcinoma (RCC). The present study found that vimentin, a mesenchymal marker, was accordingly upregulated, and E-cadherin, an epithelial marker, was downregulated in RCC patients with low vitamin D status. Thus, we investigated the effects of calcitriol or vitamin D3, an active form of vitamin D, on epithelial-mesenchymal transition (EMT) in RCC cells. RCC cells were treated by two models. In model 1, three RCC cell lines, ACHN, 786-O and CAKI-2, were incubated with either LPS (2.0 µg/mL) or transforming growth factor (TGF)-ß1 (10 ng/mL) in the presence or absence of calcitriol (200 nmol/L). In model 2, two RCC cell lines, ACHN and CAKI-2, were incubated with calcitriol (200 nmol/L) only. Calcitriol inhibited migration and invasion not only in TGF-ß1-stimulated but also in TGF-ß1-unstimulated RCC cells. Moreover, calcitriol suppressed E-cadherin downregulation and vimentin upregulation not only in TGF-ß1-stimulated but also in TGF-ß1-unstimulated ACHN and CAKI-2 cells. Calcitriol attenuated LPS-induced upregulation of MMP-2, MMP-7, MMP-9, MMP-26 and urokinase-type plasminogen activator (u-PA) in ACHN cells. In addition, calcitriol blocked TGF-ß1-induced nuclear translocation of ZEB1, Snail and Twist1 in ACHN and CAKI-2 cells. Mechanistically, calcitriol suppressed EMT through different signaling pathways: (i) calcitriol suppressed Smad2/3 phosphorylation by reinforcing physical interaction between vitamin D receptor (VDR) and Smad3 in TGF-ß1-stimulated RCC cells; (ii) calcitriol inhibited signal transducer and activator of transcription (STAT)3 activation in LPS-stimulated RCC cells; (iii) calcitriol inhibited ß-catenin/TCF-4 activation by promoting integration of VDR with ß-catenin in TGF-ß1-unstimulated RCC cells. Taken together, calcitriol inhibits migration and invasion of RCC cells partially by suppressing Smad2/3-, STAT3- and ß-catenin-mediated EMT.

Tumor-suppressor Fbxw7 targets SIK2 for degradation to interfere with TORC2-AKT signaling in pancreatic cancer.

The tumor suppressor F-box/WD repeat-containing protein 7 (Fbxw7) is a substrate-recognition subunit of a ubiquitin ligase complex. We have previously proposed that Fbxw7 inhibited pancreatic cancer cell proliferation and invasion by targeting ß-catenin. To identify other targets of Fbxw7 involved in pancreatic carcinogenesis, we screened the human protein database for Fbxw7 target candidates using the conserved Fbxw7-recognizing sequences. Twenty-three candidates are identified, including five known Fbxw7 targets and two cancer-related genes (salt inducible kinase 2 [SIK2] and ZMIZ1). We identified SIK2 as an Fbxw7 target for degradation by binding to the "TPPPS" motif of SIK2 in pancreatic cancer cells. We also demonstrated that SIK2 promoted proliferation and mitotic progression of pancreatic cancer cells. Moreover, endogenous Fbxw7 downregulates SIK2 protein level for controlling cell cycle progression, possibly by interfering the SIK2/TORC2/AKT signaling pathway to modulate p21 expression. Collectively, these data demonstrate that Fbxw7 targets the cell cycle controller, SIK2, for degradation, thereby leading to the disruption of downstream TORC2/AKT signaling to inhibit pancreatic cancer cell proliferation and cell cycle progression.

Nomograms for predicting survival in patients with metastatic gastric adenocarcinoma who undergo palliative gastrectomy.

BACKGROUND: Recently, evidence has emerged that palliative gastrectomy in patients with stage IV gastric cancer may offer some survival benefits. However, the decision whether to perform primary tumor surgery remains challenging for surgeons, and investigations into models that are predictive of prognosis are scarce. Current study aimed to develop and validate prognostic nomograms for patients with metastatic gastric adenocarcinoma treated with palliative gastrectomy. METHODS: The development dataset comprised 1186 patients from the Surveillance, Epidemiology, and End Results Program who were diagnosed with metastatic gastric adenocarcinoma in 2004-2011, while the validation dataset included 407 patients diagnosed in 2012-2015. Variables were incorporated into a Cox proportional hazards model to identify independent risk factors for survival. Both pre- and postoperative nomograms for predicting 1- or 2-year survival probabilities were constructed using the development dataset. The concordance index (c-index) and calibration curves were plotted to determine the accuracy of the nomogram models. Finally, the cut-off value of the calculated total scores based on preoperative nomograms was set and validated by comparing survival with contemporary cases without primary tumor surgery. RESULTS: Age, tumor size, location, grade, T stage, N stage, metastatic site, scope of gastrectomy, number of examined lymph node(s), chemotherapy and radiotherapy were risk factors of survival and were included as variables in the postoperative nomogram; the c-indices of the development and validation datasets were 0.701 (95% confidence interval [CI]: 0.693-0.710) and 0.699 (95% CI: 0.682-0.716), respectively. The preoperative nomogram incorporated age, tumor size, location, grade, depth of invasion, regional lymph node(s) status, and metastatic site. The c-indices for the internal (bootstrap) and external validation sets were 0.629 (95% CI: 0.620-0.639) and 0.607 (95% CI: 0.588-0.626), respectively. Based on the preoperative nomogram, patients with preoperative total score > 28 showed no survival benefit with gastrectomy compared to no primary tumor surgery. CONCLUSIONS: Our survival nomograms for patients with metastatic gastric adenocarcinoma undergoing palliative gastrectomy can assist surgeons in treatment decision-making and prognostication.

Efficacy and safety of recombinant human lymphotoxin-α derivative with cisplatin and fluorouracil in patients with metastatic esophageal squamous cell carcinoma: A randomized, multicenter, open-label, controlled, phase 2b trial.

BACKGROUND: Recombinant human lymphotoxin-α derivative (rhLTα-Da) is a lymphotoxin-α derivative that is missing 27 N-terminal amino acid residues. Previous studies indicated a benefit from the addition of rhLTα-Da to cisplatin-based treatment in patients with metastatic esophageal squamous cell carcinoma. The current study was conducted to evaluate the efficacy and safety of rhLTα-Da plus cisplatin and fluorouracil (PF) in patients with mESCC. METHODS: Patients from 15 centers in China were randomly assigned (1:1:1) to 3 arms (arm A, PF plus 10 µg/m2 daily rhLTα-Da; arm B, PF plus 20 µg/m2 daily rhLTα-Da; arm C, PF alone). The primary endpoints included progression-free survival (PFS) and the confirmed overall response rate (ORR). An exploratory analysis was performed to evaluate the role of serum tumor necrosis factor receptor II (TNFR II) in predicting the efficacy of rhLTα-Da. RESULTS: Between September 2010 and May 2013, 150 patients were enrolled. No significant differences in either PFS or ORR were observed between the 3 arms. However, in a small subset of patients who had low serum TNFR II levels, the median PFS was significantly longer for those in arm B than for these in other 2 arms (7.2 months [95% confidence interval, 5.1-8.6 months] for arm B vs 3.5 months [95% confidence interval, 1.7-5.5 months] for arm A [P = .022] and 4.0 months [95% confidence interval, 3.2-6.3 months] for arm C [P = .027]). The addition of rhLTα-Da significantly increased the incidence of chills (P < .001). CONCLUSIONS: rhLTα-Da combined with the PF regimen failed to improve PFS and ORR in patients with mESCC, except in a small subset that had low serum TNFR II concentrations. Cancer 2017;123:3986-94. © 2017 American Cancer Society.

The Effects of Molecular Properties on Ready Biodegradation of Aromatic Compounds in the OECD 301B CO2 Evolution Test.

Ready biodegradation is the primary biodegradability of a compound, which is used for discriminating whether a compound could be rapidly and readily biodegraded in the natural ecosystems in a short period and has been applied extensively in the environmental risk assessment of many chemicals. In this study, the effects of 24 molecular properties (including 2 physicochemical parameters, 10 geometrical parameters, 6 topological parameters, and 6 electronic parameters) on the ready biodegradation of 24 kinds of synthetic aromatic compounds were investigated using the OECD 301B CO2 Evolution test. The relationship between molecular properties and ready biodegradation of these aromatic compounds varied with molecular properties. A significant inverse correlation was found for the topological parameter TD, five geometrical parameters (Rad, CAA, CMA, CSEV, and N c), and the physicochemical parameter K ow, and a positive correlation for two topological parameters TC and TVC, whereas no significant correlation was observed for any of the electronic parameters. Based on the correlations between molecular properties and ready biodegradation of these aromatic compounds, the importance of molecular properties was demonstrated as follows: geometrical properties > topological properties > physicochemical properties > electronic properties. Our study first demonstrated the effects of molecular properties on ready biodegradation by a number of experiment data under the same experimental conditions, which should be taken into account to better guide the ready biodegradation tests and understand the mechanisms of the ready biodegradation of aromatic compounds.

A comparative study of biodegradability of a carcinogenic aromatic amine (4,4'-diaminodiphenylmethane) with OECD 301 test methods.

4,4'-Diaminodiphenylmethane (MDA) is a widely used compound in industries. Studies on the biodegradability of MDA are necessary for environmental hazard identification and risk assessment. Previous studies have suggested that MDA was not readily biodegradable. In the present study, three batches of biodegradation tests (OECD 301A, B, D and F tests) were performed on MDA in June, August and December of 2012. MDA was found to be readily biodegradable and produced colored intermediates in the 301A, B and F test systems. MDA biodegradation measurements were consistent among the three batches of tests. Differences in the extent of biodegradation determined in different methods originated from different test conditions and assessment endpoints. The 301D test has stringent test conditions and is usually performed on chemicals that are toxic to microorganisms, so the test results obtained from 301D tests are less meaningful for evaluating the biodegradability of MDA. The low MDA biodegradation measurements in the 301B tests compared to the 301A and F tests were due to the assessment method, which did not account for MDA incorporation into biomass in its calculation of CO2 formation rate. The differences in the biodegradation rates, as measured by the different OECD 301 test systems, could also be related to the structure and properties of the chemical. For test substances that can be assessed by all OECD 301 test methods, the highest biodegradation values may be obtained from the 301A and F test methods. This study provides new information to assess the environmental fate in the risk assessment of MDA.

Emission of odorous volatile organic compounds from a municipal manure treatment plant and their removal using a biotrickling filter.

Odorous volatile organic compounds (VOCs) from municipal manure treatment facilities are considered as a major nuisance issue for operators and nearby residents. In this study, up to 71 odorous VOCs were detected by gas chromatography-mass spectrometry at the manure treatment plant. These compounds can be classified into five different categories, including alkanes, olefins, aromatics, volatile organosulphur compounds and terpenes. Toluene, dimethyl disulphide, dimethyl sulphide, xylene and ethylbenzene were the five most abundant pollutants. A pilot-scale biotrickling filter (BTF) was employed to treat the complex odorous gases. Correlation analysis showed that the removal efficiency (RE) of the BTF was related with the molecular weight and chemical structure of contaminants. Higher than 85% of REs could be reached for aromatic, terpenes and most alkanes compounds after 180 days of operation. Comparatively, most olefins and partial alkanes compounds with a molecular weight lower than 70 were not removed easily. The REs of these compounds ranged from 0% to 94%, and the average removal efficiency (RE) was only about 33.3%.

Quantitative assessment of the association between miR-196a2 rs11614913 polymorphism and gastrointestinal cancer risk.

Published data on the association between miR-196a2 rs11614913 polymorphism and risk of gastrointestinal (GI) cancers are inconsistent among studies. To clarify the association, we performed a comprehensive literature search and a meta-analysis. We searched multiple databases to identify genetic association studies investigating the effect of miR-196a2 rs11614913 polymorphism on GI cancers with the last report up to January 18, 2012. The odds ratio (OR) and its 95 % confidence interval (95 % CI) were calculated to assess the strength of association. A total of 13 studies including 4,947 cases and 5,642 controls based on the search criteria were involved in this meta-analysis. In the overall analysis, it was suggested that variant C allele of miR-196a2 rs11614913 polymorphism could significantly increase risk of GI cancers in different genetic models (C vs T: OR = 1.17, 95 % CI = 1.07-1.28, P = 0.0008; CT + CC vs TT: OR = 1.26, 95 % CI = 1.08-1.48, P = 0.004; CC vs CT + TT: OR = 1.23, 95 % CI = 1.08-1.39, P = 0.002; CC vs TT: OR = 1.55, 95 % CI = 1.24-1.94, P = 0.0001; CT vs TT: OR = 1.20, 95 % CI = 1.02-1.40, P = 0.03). When stratified by ethnicity, we found a significant association in Asian population, as well as Caucasian population. When stratified by cancer types, we found a significant association in colorectal cancer, as well as esophageal cancer. We did not find a significant association between miR-196a2 rs11614913 polymorphism and hepatocellular carcinoma risk. For gastric cancer, a significantly increased cancer risk was observed only in homozygote comparison. This meta-analysis demonstrates that miR-196a2 rs11614913 polymorphism is significantly associated with risk of GI cancers.

Microchip-based immunoassays with application of silicon dioxide nanoparticle film.

Highly sensitive detection of proteins offers the possibility of early and rapid diagnosis of various diseases. Microchip-based immunoassay integrates the benefits from both immunoassays (high specificity of target sample) and microfluidics (fast analysis and low sample consumption). However, direct capture of proteins on bare microchannel surface suffers from low sensitivity due to the low capacity of microsystem. In this study, we demonstrated a microchip-based heterogeneous immunoassay using functionalized SiO(2) nanoparticles which were covalently assembled on the surface of microchannels via a liquid-phase deposition technique. The formation of covalent bonds between SiO(2) nanoparticles and polydimethylsiloxane substrate offered sufficient stability of the microfluidic surface, and furthermore, substantially enhanced the protein capturing capability, mainly due to the increased surface-area-to-volume ratio. IgG antigen and FITC-labeled anti-IgG antibody conjugates were adopted to compare protein-enrichment effect, and the fluorescence signals were increased by ~75-fold after introduction of functionalized SiO(2) nanoparticles film. Finally, a proof-of-concept experiment was performed by highly efficient capture and detection of inactivated H1N1 influenza virus using a microfluidic chip comprising highly ordered SiO(2) nanoparticles coated micropillars array. The detection limit of H1N1 virus antigen was 0.5 ng mL(-1), with a linear range from 20 to 1,000 ng mL(-1) and mean coefficient of variance of 4.71%.

A Novel Nomogram Combining Alternative Splicing Events and Clinical Factors for Prognosis Prediction in Head and Neck Squamous Cell Carcinoma.

Due to limitations of sensitive biomarkers, the clinical prognosis of patients with head and neck squamous cell carcinoma (HNSCC) remains poor. Alternative splicing (AS) is the basis of both transcriptome and proteome richness, so more and more evidence indicates an important relationship between AS and tumor progression. The aim of this study was to offer a comprehensive analysis on AS events and then investigate its potentials as a new biomarker for patients with squamous cell carcinoma of the head and neck. In this study, univariate assays were conducted to examine the prognosis-associated AS events, and we screened 4068 survival-related AS events in 2573 genes. Then, the AS events related to survival were further determined and analyzed using LASSO regression and multivariate assays, and an eleven-AS signature was developed. Kaplan-Meier assays indicated patients with high-risk scores exhibited a shorter OS than those with low-risk scores. Multivariate assays further demonstrated that the signature's risk score was independent of HNSCC survivals. Meanwhile, we analyzed the clinical association of AS-based prognostic signature in HNSCC patients and observed that tumor specimens with advanced stages and grades exhibited a high risk score. In addition, the results of survival nomogram revealed that predicted outcomes and actual outcomes were highly consistent. Overall, our group showed an eleven-AS signature of HNSCC, which could be regarded as a separate prognostic factor.

Rhizobium borbori sp. nov., aniline-degrading bacteria isolated from activated sludge.

Three aniline-degrading bacteria, strains DN316(T), DN316-1 and DN365, were isolated from activated sludge. According to 16S rRNA gene sequence-based phylogenetic analysis, the isolates belonged to the genus Rhizobium, with Rhizobium ( = Agrobacterium) radiobacter LMG 140(T) as the closest relative, with 96.5 % sequence similarity. Phylogenetic analysis of the representative strain DN316(T) using sequences of the glnA, thrC and recA genes and the 16S-23S intergenic spacer region confirmed the phylogenetic arrangement obtained from analysis of the 16S rRNA gene. DNA-DNA relatedness between DN316(T) and R. radiobacter LMG 140(T) was 43.7 %, clearly indicating that the representative strain DN316(T) represents a novel species. Phenotypic and biochemical characterization of the isolates and insertion sequence-PCR fingerprinting patterns showed several distinctive features that differentiated them from closely related species. The major components of the cellular fatty acids were C(18 : 1)ω7c (57.10 %), C(16 : 0) (11.31 %) and C(19 : 0) cyclo ω8c (10.13 %). Based on our taxonomic analysis, the three isolates from activated sludge represent a novel species of the genus Rhizobium, for which the name Rhizobium borbori sp. nov. is proposed. The type strain is DN316(T) ( = CICC 10378(T)  = LMG 23925(T)).

[Efficacy and safety of palonosetron versus tropisetron in the prevention of highly emetogenic chemotherapy-induced acute and delayed vomiting in Chinese cancer patients].

OBJECTIVE: To explore the efficacy and safety of palonosetron in the prevention of acute and delayed chemotherapy-induced nausea and vomiting after moderate to severe emetogenic chemotherapy. METHODS: From November 2008 to November 2009, a multicenter, randomized, double-blind and self-crossover phase II clinical trial with a total planned enrollment of 160 patients was carried out to compare palonosetron (drug A) with tropisetron (drug B). The subjects were randomized divided into groups AB and BA. The dosing sequence in the group AB was drug A the first cycle and drug B the second cycle while the BA group was administered reversely. The efficacy was evaluated within a period of 5 days after cisplatin or adriamycin-based regimen chemotherapy. Adverse effects were assessed by CTCAE 3.0. RESULTS: Among 155 enrolled cases, 132 cases were assessable for efficacy. The complete control rate of acute chemotherapy-induced nausea and vomiting was 54.55% vs 51.52% for drug A vs drug B (P > 0.05), but that of delayed reaction was 53.03% vs 38.64% respectively. There were significant differences (P = 0.01). Meanwhile, the rate of adverse effects was 4.90% for investigational agent without severe adverse events. The main adverse reactions were headache and dizziness. CONCLUSION: With a high safety profile, palonosetron is an effective agent for the prevention of acute and delayed chemotherapy-induced nausea and vomiting.

[Study on optimization of formulation of Danggui Liuhuang effervescent granules].

OBJECTIVE: To optimize the formulation of Danggui Liuhuang effervescent granules. METHODS: By means of quadratic regression rotation-orthogonal combination design, the effect of the proper proportion between citric acid and sodium bicarbonate, as well as the proper quantity of polyethylene glycol 6000 and sodium cyclamate on the dissolubility and pH of effervescent granules was studied. RESULTS: The best formulation was as follows: citric acid: sodium bicarbonate = 0.75: 1, the percentage of polyethylene glycol 6000 and cyclamate was 3.25% and 0.89%, respectively. CONCLUSION: The dissolubility and pH of the effervescent granules are better and the taste is satisfactory.

Design and synthesis of 7-O-1,2,3-triazole hesperetin derivatives to relieve inflammation of acute liver injury in mice.

Based on the previous research results of our research group, to further improve the anti-inflammatory activity of hesperetin, we substituted triazole at the 7-OH branch of hesperetin. We also evaluated the anti-inflammatory activity of 39 new hesperetin derivatives. All compounds showed inhibitory effects on nitric oxide (NO) and inflammatory factors in lipopolysaccharide-induced RAW264.7 cells. Compound d5 showed a strong inhibitory effect on NO (half maximal inhibitory concentration = 2.34 ± 0.7 µM) and tumor necrosis factor-α, interleukin (IL)-1ß, and (IL-6). Structure-activity relationships indicate that 7-O-triazole is buried in a medium-sized hydrophobic cavity that binds to the receptor. Compound d5 can also reduce the reactive oxygen species production and significantly inhibit the expression of inducible NO synthase and cyclooxygenase-2 through the nuclear factor-κB signaling pathway. In vivo results indicate that d5 can reduce liver inflammation in mice with acute liver injury (ALI) induced by CCI4. In conclusion, d5 may be a candidate drug for treating inflammation associated with ALI.

Application of Paclitaxel-loaded EGFR Peptide-conjugated Magnetic Polymeric Liposomes for Liver Cancer Therapy.

Developing the methodologies that allow for safe and effective delivery of therapeutic drugs to target sites is a very important research area in cancer therapy. In this study, polyethylene glycol (PEG)-coated magnetic polymeric liposome (MPL) nanoparticles (NPs) assembled from octadecyl quaternized carboxymethyl chitosan (OQC), PEGylated OQC, cholesterol, and magnetic NPs, and functionalized with epithelial growth factor receptor (EGFR) peptide, were successfully prepared for in-vivo liver targeting. The two-step liver targeting strategy, based on both magnetic force and EGFR peptide conjugation, was evaluated in a subcutaneous hepatocellular carcinoma model of nude mouse. The results showed that EGFR-conjugated MPLs not only accumulated in the liver by magnetic force, but could also diffuse into tumor cells as a result of EGFR targeting. In addition, paclitaxel (PTX) was incorporated into small EGFR-conjugated MPLs (102.0±0.7 nm), resulting in spherical particles with high drug encapsulation efficiency (>90%). The use of the magnetic targeting for enhancing the transport of PTX-loaded EGFR-conjugated MPLs to the tumor site was further confirmed by detecting PTX levels. In conclusion, PTX-loaded EGFR-conjugated MPLs could potentially be used as an effective drug delivery system for targeted liver cancer therapy.

Reactive oxygen species-mediated cellular genotoxic stress is involved in 1-nitropyrene-induced trophoblast cycle arrest and fetal growth restriction.

1-nitropyrene (1-NP) is a key component of diesel exhaust-sourced fine particulate matter (PM2.5). Our recent study demonstrated that gestational 1-NP exposure caused placental proliferation inhibition and fetal intrauterine growth restriction (IUGR). This study aimed to investigate the role of genotoxic stress on 1-NP-induced placental proliferation inhibition and fetal IUGR. Human trophoblasts were exposed to 1-NP (10 µM). Growth index was reduced and PCNA was downregulated in 1-NP-exposed placental trophoblasts. More than 90% of 1-NP-exposed trophoblasts were arrested in either G0/G1 or G2/M phases. CDK1 and cyclin B, two G2/M cycle-related proteins, and CDK2, a G0/G1 cycle-related protein, were reduced in 1-NP-exposed trophoblasts. Phosphorylated Rb, a downstream molecule of CDK2, was inhibited in 1-NP-exposed trophoblasts. Moreover, DNA double-strand break was observed and γ-H2AX, another indicator of DNA double-strand break, was upregulated in 1-NP-exposed trophoblasts. Phosphorylated ATM, a key molecule of genotoxic stress, and its downstream molecule Chk2 were elevated. By contrast, Cdc25A, a downstream target of Chk2, was reduced in 1-NP-exposed trophoblasts. Phenyl-N-t-butylnitrone (PBN), a free radical scavenger, inhibited 1-NP-induced genotoxic stress and trophoblast cycle arrest. Animal experiment showed that N-acetylcysteine (NAC), an antioxidant, rescued 1-NP-induced placental proliferation inhibition and fetal IUGR in mice. These results provide evidence that reactive oxygen species (ROS)-mediated cellular genotoxic stress partially contributes to 1-NP-induced placental proliferation inhibition and fetal IUGR.

Energy generation coupled to azoreduction by membranous vesicles from Shewanella decolorationis S12.

Previous studies have demonstrated that Shewanella decolorationis S12 can grow on the azo compound amaranth as the sole electron acceptor. Thus, to explore the mechanism of energy generation in this metabolism, membranous vesicles (MVs) were prepared and the mechanism of energy generation investigated. The membrane, which was fragmentized during preparation, automatically formed vesicles ranging from 37.5-112.5 nm in diameter under electron micrograph observation. Energy was conserved when coupling the azoreduction by the MVs of an azo compound or Fe(III) as the sole electron acceptor with H2, formate, or lactate as the electron donor. The amaranth reduction by the vesicles was found to be inhibited by specific respiratory inhibitors, including Cu(2+) ions, dicumarol, stigmatellin, and metyrapone, indicating that the azoreduction was indeed a respiration reaction. This finding was further confirmed by the fact that the ATP synthesis was repressed by the ATPase inhibitor N,N'-dicyclohexylcarbodiimide (DCCD). Therefore, this study offers solid evidence of a mechanism of microbial dissimilatory azoreduction on a subcell level.

Cumulative Score Based on Preoperative Fibrinogen and Pre-albumin Could Predict Long-term Survival for Patients with Resectable Gastric Cancer.

Background: To investigate the prognostic significance of the cumulative score based on preoperative fibrinogen and pre-albumin (FP score) in patients with gastric cancer after radical gastrectomy. Methods: Baseline characteristics, preoperative fibrinogen and pre-albumin levels were retrospectively reviewed in patients who underwent radical gastrectomy. The optimal cut-off values for fibrinogen and pre-albumin were defined as 4.0 g/L and 230.0 mg/L, respectively. Patients with elevated fibrinogen (≥ 4.0 g/L) and decreased pre-albumin (< 230.0 mg/L) levels were allocated an FP score of 2, those with only one of these two abnormalities were assigned a score of 1, and those with neither of the two abnormalities were allocated a score of 0. The prognostic value was examined by univariate and multivariate regression analyses. Results: The preoperative FP score was significantly correlated with age, tumor size, fibrinogen level, pre-albumin level and white blood cell count. No significant differences based on sex, tumor location, degree of differentiation, depth of invasion, lymph node status, tumor-node-metastasis (TNM) stage or adjuvant chemotherapy were identified between the groups. In addition, univariate survival analysis revealed that a high preoperative FP score was significantly associated with unfavorable disease-free survival (DFS) [hazard ratio (HR), 1.482; 95% confidence interval (CI), 1.222-1.796; P < 0.001] and overall survival (OS) (HR, 1.623; 95% CI, 1.315-2.002; P < 0.001). Moreover, after adjusting for other factors, a high preoperative FP score remained an independent predictor for impaired DFS (HR, 1.434; 95% CI, 1.177-1.747; P < 0.001) and OS (HR, 1.413; 95% CI, 1.136-1.758; P = 0.002) in multivariate Cox regression analysis. Conclusions: The preoperative FP score significantly predicts long-term survival for gastric cancer patients who have undergone radical gastrectomy.

The Vitamin D status is associated with serum C-reactive protein and adhesion molecules in patients with renal cell carcinoma.

Low vitamin D status is associated with an increased risk of renal cell carcinoma (RCC). This study investigated the association of vitamin D status with serum C-reactive protein (CRP) and adhesion molecules among RCC patients. Fifty newly diagnosed RCC patients and 100 age- and sex-matched controls were recruited. As expected, serum 25(OH)D level was lower in RCC patients than in controls. By contrast, serum levels of CRP, an inflammatory molecule, and ICAM, LAMA4 and EpCAM, three adhesion molecules, were higher in RCC patients than in controls. All RCC patients were divided into two groups: H-VitD (>20 ng/ml) or L-VitD (<20 ng/ml). Interestingly, the levels of serum CRP and all adhesion molecules were higher in RCC patients with L-VitD than those with H-VitD. Nuclear vitamin D receptor (VDR) was downregulated and nuclear factor kappa B (NF-κB) was activated in cancerous tissues. The in vitro experiments found that VitD3 suppressed NF-κB activation and adhesion molecules in RCC cells. Moreover, VitD3 suppressed NF-κB through reinforcing physical interaction between VDR and NF-κB p65 subunit in RCC cells. These results provide a mechanistic explanation for the association among low vitamin D status, local inflammation and increased expression of adhesion molecules among RCC patients.