Protein Kinase N1 Level Predicts Acute Kidney Injury in Patients Undergoing Cardiac Surgery: A Prospective Cohort Study.

INTRODUCTION: The objective of this study was to examine the utility of protein kinase N1 (PKN1) as a biomarker of cardiac surgery-associated AKI (CSA-AKI). METHODS: A prospective cohort study of 110 adults undergoing on-pump cardiac surgery was conducted. The associations between post-operative PKN1 and CSA-AKI, AKI severity, need for renal replacement therapy (RRT), duration of AKI, length of ICU stay, and post-operative hospital stay were evaluated. RESULTS: Patients were categorized into three groups according to PKN1 tertiles. The incidence of CSA-AKI in the third tertile was 3.4-fold higher than that in the first. PKN1 was an independent risk factor for CSA-AKI. The discrimination of PKN1 to CSA-AKI assessed by ROC curve indicated that the AUC was 0.70, and the best cutoff was 5.025 ng/mL. This group (>5.025 ng/mL) was more likely to develop CSA-AKI (p < 0.001). The combined AUC of EuroSCORE, aortic cross-clamp time, and PKN1 was 0.82 (p < 0.001). A higher level of PKN1 was related to increased need for RRT, longer duration of AKI, and length of ICU and post-operative hospital stays. CONCLUSIONS: PKN1 could be a potential biomarker for the prediction of CSA-AKI. The combination of PKN1, EuroSCORE, and aortic cross-clamp time was likely to predict the occurrence of CSA-AKI.

Integrative analysis of chloroplast genome, chemicals, and illustrations in Bencao literature provides insights into the medicinal value of Peucedanum huangshanense.

The genus Peucedanum L. (Apiaceae) is a large group comprising more than 120 species distributed worldwide. Many plants of the genus Peucedanum have been studied and used in traditional Chinese medicine. In 2020, a new species, Peucedanum huangshanense Lu Q. Huang, H. S. Peng & S. S. Chu, was found in the Huangshan Mountains of Anhui Province, China. However, little is known about its medicinal properties. Thus, the objective of this study is to explore the potential medicinal value of P. huangshanense and its relationship with other Peucedanum species. Through textual research on illustrations of Qianhu in Bencao literature, it can be inferred that at least five species of genus Peucedanum have been used in Chinese medicine. Therefore, we chose these five species of Peucedanum and P. huangshanense together for subsequent research. We conducted morphological, chloroplast genome, and chemical analyses of six Peucedanum species, including the newly discovered P. huangshanense. The chloroplast genomes of Peucedanum showed a typical tetrad structure, and the gene structure and content were similar and conservative. There were significant differences in genome size and the expansion of the inverted repeat boundary. Through nucleotide polymorphism analysis, we screened 14 hotspot mutation regions that have the potential to be used as specific molecular markers for the taxonomy of Peucedanum. Our results showed an inversion of the trnD-trnY-trnE gene in the P. huangshanense chloroplast genome, which can be developed as a specific molecular marker for species identification. Phylogenetic analysis showed that the phylogenetic trees had high support and resolution, which strongly supports the view that Peucedanum is not a monophyletic group. P. huangshanense had the closest genetic relationship to P. ampliatum K. T. Fu, followed by P. harry-smithii Fedde ex Wolff. Furthermore, the main coumarins of P. huangshanense were most similar to those of P. japonicum Thunb. and P. harry-smithii. In summary, our research lays a foundation for the systematic classification of Peucedanum and sheds light on the medicinal value of P. huangshanense.

Laccase encapsulation immobilized in mesoporous ZIF-8 for enhancement bisphenol A degradation.

Endocrine disruptors (EDCs) such as bisphenol A (BPA) have many adverse effects on environment and human health. Laccase encapsulation immobilized in mesoporous ZIF-8 was prepared for efficient degradation of BPA. The ZIF-8 (PA) with highly ordered mesopores was synthesized using trimethylacetic acid (PA) as a template agent. On account of the improvement of skeletal stability by cross-linking agent glutaraldehyde, ZIF-8 (PA) realized laccase (FL) immobilization within the mesopores through encapsulation strategy. By replacing the template agent, the effect of pore size on the composite activity and immobilization efficiency by SEM characterization and kinetic analysis were investigated. Based on the physical protection of ZIF-8(PA) on laccase, as well as electrostatic interactions between substances and changes in surface functional groups (e.g. -OH, etc.), multifaceted enhancement including activity, stability, storability were engendered. FL@ZIF-8(PA) could maintain high activity in complex systems at pH 3-11, 10-70 °C or in organic solvent containing system, which exhibited an obvious improvement compared to free laccase and other reported immobilized laccase. Combined with TGA, FT-IR and Zeta potential analysis, the intrinsic mechanism was elaborated in detail. On this basis, FL@ZIF-8(PA) achieved efficient removal of BPA even under adverse conditions (removal rates all above 55% and up to 90.28%), and was suitable for a wide range of initial BPA concentrations. Combined with the DFT calculations on the adsorption energy and differential charge, the mesoporous could not only improve the enrichment performance of BPA on ZIFs, but also enhance the interaction stability. Finally, FL@ZIF-8(PA) was successfully applied to the degradation of BPA in coal industry wastewater. This work provides a new and ultra-high performances material for the organic pollution treatment in wastewater.

Water-stable metal organic framework-199@polyaniline with high-performance removal of copper II.

Metal organic frameworks (MOFs)-based adsorbents for copper ion (Cu2+) generally have the disadvantages of instability in water, low adsorption capacity, and selectivity. Aimed at such problems, we fabricated MOF-199 coated with polyaniline (MOF-199@PANI, core@shell) composite for specific adsorption of Cu2+ in water efficiently. Combined with the characterization by SEM, XRD, and FT-IR, the comprehensively excellent performance probably derived from porous structures of MOF-199, as well as the complexation between Cu2+ and the N atoms of imine moieties in PANI. In addition, the coating process by PANI perfectly protected the MOF skeleton. The isothermal data fitted well to Langmuir isotherm model, of which the calculated adsorption capacity reached 7831.34 mg/g. It was one or two orders of magnitude higher than some other new absorbent for Cu2+ including some carbon-based or organic adsorbents. On the basis of the optimization including pH value, temperature, and ratio of raw materials, the fabricated composite has realized the removal of the spiked Cu2+ in actual fresh water and industrial wastewater samples.

Investigation of microplastics in sludge from five wastewater treatment plants in Nanjing, China.

Municipal wastewater treatment plants (WWTPs) have been regarded as the main receptors of microplastics in industrial and domestic wastewater. The excess sludge they generate is an important carrier for the microplastics to enter the environment. In China, relevant regional studies are still in an initial phase. In this work, microplastics in the sewage sludges at different sampling points of five WWTPs in Nanjing City (an important city in the Yangtze River basin) were investigated, including their abundance, morphology and chemical composition. Furthermore, the influence factors such as population density, economic development level, wastewater source and treatment process were also discussed. The analysis results through optical microscope and FT-IR showed that the detected microplastics were divided into fragments, films, fibers and granules. Their chemical component reached up to 19 species, including small amounts of petroleum resins which was scarcely detected in other studies. Wastewater source was the primary factor influencing the microplastic abundance and size in sludge. And the microplastic shape and chemical components were closely related to the industrial type. Furthermore, because the removal effect on the microplastics with different morphologies were varied with the treatment process, the preliminary suggestions on the technology for particular wastewater were proposed. This study provides partial regional data and analysis for the microplastics contained in the sludge of WWTPs, expecting to provide a certain theoretical support for the operations management of WWTPs and standardized sludge treatment.

A translational study of Galectin-3 as an early biomarker and potential therapeutic target for ischemic-reperfusion induced acute kidney injury.

PURPOSE: We evaluated Galectin-3 (Gal-3) as a potential early biomarker of acute kidney disease (AKI), and the effect of Gal-3 inhibition by modified citrus pectin (P-MCP) on renal ischemia/reperfusion (I/R) induced AKI. METHODS: Among fifty-two post-cardiac surgery patients, serum and urine Gal-3 levels were examined on intensive care unit (ICU) admission. In a rat renal I/R injury model, Gal-3 levels, renal function, and histopathology were evaluated in rats pretreated with P-MCP for one week (n = 16) compared to controls (n = 16). RESULTS: Among post-cardiac surgery patients, median serum and urine Gal-3 levels on ICU admission were higher in patients who developed AKI than those who did not (AKI vs non-AKI serum: 18.37 vs. 8.08 ng/ml, p < 0.001; AKI vs non-AKI urine:13.27 vs. 6.27 ng/ml, p < 0.001). Serum and urine Gal-3 levels were reliable biomarkers for detecting AKI (AUC: 0.88 and 0.87). In the rat renal I/R injury model, I/R caused an increase of Gal-3 at 0.5 h after reperfusion (p < 0.05). Gal-3 inhibition by P-MCP significantly decreased Gal-3 release and expression (p < 0.05), reduced interleukin (IL-6) release (p < 0.05), decreased renal dysfunction, and reduced renal tubular injury. CONCLUSIONS: Gal-3 is a potential early biomarker in the diagnosis of AKI. Inhibition of Gal-3 may provide therapeutic utility in the treatment of I/R-induced AKI.

Galectin-3 in septic acute kidney injury: a translational study.

BACKGROUND: Galectin-3 (Gal-3) is a pleiotropic glycan-binding protein shown to be involved in sepsis and acute kidney injury (AKI). However, its role has never been elucidated in sepsis-associated AKI (S-AKI). We aimed to explore Gal-3's role and its potential utility as a therapeutic target in S-AKI. METHODS: In 57 patients admitted to the intensive care unit (ICU) with sepsis, serum Gal-3 was examined as a predictor of ICU mortality and development of AKI. In a rat model of S-AKI induced by cecal ligation and puncture (CLP), 7-day mortality and serum Gal-3, Interleukin-6 (IL-6), and creatinine were examined at 2, 8, and 24 hours (h) post-CLP. Two experimental groups received the Gal-3 inhibitor modified citrus pectin (P-MCP) at 400 mg/kg/day and 1200 mg/kg/day, while the control group received water only (n = 18 in each group). RESULTS: Among 57 patients, 27 developed AKI and 8 died in the ICU. Serum Gal-3 was an independent predictor of AKI (OR = 1.2 [95% CI 1.1-1.4], p = 0.01) and ICU mortality (OR = 1.4 [95% CI 1.1-2.2], p = 0.04) before and after controlling for age, AKI, and acute physiology and chronic health evaluation (APACHE II) score. In the CLP rat experiment, serum Gal-3 peaked earlier than IL-6. Serum Gal-3 was significantly lower in both P-MCP groups compared to control at 2 h post-CLP (400 mg: p = 0.003; 1200 mg: p = 0.002), and IL-6 was significantly lower in both P-MCP groups at all time points with a maximum difference at 24 h post-CLP (400 mg: p = 0.015; 1200 mg: p = 0.02). In the Gal-3 inhibitor groups, 7-day mortality was significantly reduced from 61% in the control group to 28% (400 mg P-MCP: p = 0.03) and 22% (1200 mg P-MCP: p = 0.001). Rates of AKI per RIFLE criteria were significantly reduced from 89% in the control group to 44% in both P-MCP groups (400 mg: p = 0.007; 1200 mg: p = 0.007). CONCLUSIONS: This translational study demonstrates the importance of Gal-3 in the pathogenesis of S-AKI, and its potential utility as a therapeutic target.

Abundance, morphology, and removal efficiency of microplastics in two wastewater treatment plants in Nanjing, China.

Municipal wastewater treatment plants (WWTPs) are considered to be major contributors of microplastics to the aquatic environment. Detailed research in China, which is relevant to the local situation, remains in the initial stage. Herein, the microplastic abundance, morphology, and removal efficiency of two WWTPs (C and P) equipped with tertiary treatment processes in different districts of Nanjing, an important city in the Yangtze River Basin, were investigated. The influence of technology, operational parameters, daily capacity, and sewage source and its proportion were discussed. Observations by optical microscope and FT-IR analysis and systematic calculation revealed that the microplastics have four shapes, including fragments, granules, film, and fibers, with various sizes and proportions, which were dependent on wastewater source. The total removal rates of 97.67% and 98.46% for WWTP C and WWTP P, respectively, indicated their highly efficient reduction of microplastics. Treatment technology had a considerable influence on the removal rate, especially the secondary and tertiary processes. However, a large number of microplastics from WWTPs were still released into the environmental waters due to the huge daily capacity. Sewage source determined the concentration, morphology feature, and chemical composition of microplastics to a certain extent. Compared with industrial wastewater, domestic wastewater possibly contained smaller microplastics of polyethylene and polypropylene with lower abundance. Furthermore, additional attention was provided on the flocculation process, drainage system, and treatment efficiency of microplastics with different shapes. This work is expected to provide some technical supports to guide the operation and management of WWTPs.

Transcriptome and metabolite profiling reveals the effects of Funneliformis mosseae on the roots of continuously cropped soybeans.

BACKGROUND: Arbuscular mycorrhizal fungi are the most widely distributed mycorrhizal fungi, which can form mycorrhizal symbionts with plant roots and enhance plant stress resistance by regulating host metabolic activities. In this paper, the RNA sequencing and ultra-performance liquid chromatography (UPLC) coupled with tandem mass spectrometry (MS/MS) technologies were used to study the transcriptome and metabolite profiles of the roots of continuously cropped soybeans that were infected with F. mosseae and F. oxysporum. The objective was to explore the effects of F. mosseae treatment on soybean root rot infected with F. oxysporum. RESULTS: According to the transcriptome profiles, 24,285 differentially expressed genes (DEGs) were identified, and the expression of genes encoding phenylalanine ammonia lyase (PAL), trans-cinnamate monooxygenase (CYP73A), cinnamyl-CoA reductase (CCR), chalcone isomerase (CHI) and coffee-coenzyme o-methyltransferase were upregulated after being infected with F. oxysporum; these changes were key to the induction of the soybean's defence response. The metabolite results showed that daidzein and 7,4-dihydroxy, 6-methoxy isoflavone (glycine), which are involved in the isoflavone metabolic pathway, were upregulated after the roots were inoculated with F. mosseae. In addition, a substantial alteration in the abundance of amino acids, phenolic and terpene metabolites all led to the synthesis of defence compounds. An integrated analysis of the metabolic and transcriptomic data revealed that substantial alterations in the abundance of most of the intermediate metabolites and enzymes changed substantially under pathogen infection. These changes included the isoflavonoid biosynthesis pathway, which suggests that isoflavonoid biosynthesis plays an important role in the soybean root response. CONCLUSION: The results showed that F. mosseae could alleviate the root rot caused by continuous cropping. The increased activity of some disease-resistant genes and disease-resistant metabolites may partly account for the ability of the plants to resist diseases. This study provides new insights into the molecular mechanism by which AMF alleviates soybean root rot, which is important in agriculture.

Transcriptomic and Proteomic Analysis Revealed the Effect of Funneliformis mosseae in Soybean Roots Differential Expression Genes and Proteins.

Glycine max is easily infected with root rot in continuous cropping systems, which can severely affect crop yield. Arbuscular mycorrhizal fungi (AMF) can reduce the incidence of root rot and increase plant height and biomass indices. However, the molecular changes that occur during soybean symbiosis with AMF remain largely unknown. To better understand the molecular mechanism underlying soybean symbiosis with AMF, we performed transcriptomic and proteomic analyses to explore the changes in protein expression during a high-incidence period (79 days) in asymbiotic and symbiotic plants and to identify the key proteins that regulate the mechanism of soybean symbiosis with AMF. A total of 10 104 genes were identified in the CK-vs-F comparison, and 11 562 genes were significantly differentially expressed in the AF group compared with the F group. A total of 9488 proteins were identified, with 256 differentially expressed proteins (DEPs) in the CK-vs-F comparison and 651 DEPs in the F-vs-AF comparison. Key pathways and DEPs were found to be involved in processes associated with "phenylalanine metabolism", "plant hormone signal transduction", "plant-pathogen interaction", and "metabolic pathways". The expression of phenylalanine ammonia-lyase (PAL), calcium-dependent protein kinase (CPK), and other defense-related proteins was upregulated by Funneliformis mosseae, indicating that inoculation promotes the development of soybean and increases disease resistance. Our results suggest that symbiosis promotes the growth and development of soybean and increases disease resistance. This study provides new insight into the molecular basis of the mechanism by which AMF affect plant disease resistance.

iTRAQ Proteomic Analysis of Continuously Cropped Soybean Root Inoculated With Funneliformis mosseae.

Soybean (Glycine max) is susceptible to root rot when subjected to continuous cropping, and this disease can seriously diminish the crop yield. Proteomics analyses can show the difference of protein expression in different treatment samples. Herein, isobaric tag for relative and absolute quantitation (iTRAQ) labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were employed for proteomic analysis of continuously cropped soybean inoculated with the arbuscular mycorrhizal fungus (AMF) Funneliformis mosseae. The AMF can reduce the incidence of root rot and increase plant height, biomass index in 1, 2, and 4 year of continuous cropping. Differential expression of proteins in soybean roots was determined following 1 year of continuous cropping. A total of 131 differentially expressed proteins (DEPs) were identified in F. mosseae-treated samples, of which 49 and 82 were up- and down-regulated, respectively. The DEPs were annotated with 117 gene ontology (GO) terms, with 48 involved in biological processes, 31 linked to molecular functions, and 39 associated with cell components. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis mapped the DEPs to 113 mainly metabolic pathways including oxidative phosphorylation, glycolysis, and amino acid metabolism. Expression of glucan 1,3-beta-glucosidase, chalcone isomerase, calcium-dependent phospholipid binding and other defense-related proteins was up-regulated by F. mosseae, suggesting inoculation promotes the growth and development of soybean and increases disease resistance. The findings provide an experimental basis for further research on the molecular mechanisms of AMF in resolving problems associated with continuous soybean cropping.

Regulation of ROS-NF-κB axis by tuna backbone derived peptide ameliorates inflammation in necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is the most common life-threatening gastrointestinal disease encountered in the premature infant. It has been shown that the intercellular reactive oxygen species (ROS) generation activated by lipopolysaccharide involved in the nuclear factor kappa B (NF-κB) activation and pathogenesis of NEC. Here, we report that an antioxidant peptide from tuna backbone protein (APTBP) reduces the inflammatory cytokines transcription and release. APTBP directly scavenges the free radical through 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) assay. In addition, APTBP reduces the intracellular ROS level, exhibiting an antioxidant activity within cells. Remarkably, gavage with APTBP attenuates the phenotype of NEC in the mice model. Mechanically, the NF-κB activation, together with the expression of inflammatory cytokines are decreased significantly when intracellular ROS are eliminated by APTBP. Therefore, our findings demonstrated that an antioxidant peptide, APTBP, ameliorates inflammation in NEC through attenuating ROS-NF-κB axis.

Does Fenoldopam Protect Kidney in Cardiac Surgery? A Systemic Review and Meta-Analysis With Trial Sequential Analysis.

PURPOSE: To assess the benefits and harms of fenoldopam for nephroprotective effects in adult patients undergoing cardiac surgery. METHODS: We conducted a systematic review with meta-analysis of randomized controlled trials (RCTs) comparing fenoldopam with placebo in cardiac surgery. Trials were systematically searched from PubMed, EMBASE, CENTRAL, and CNKI databases, up to July 30, 2018. A trial sequential analysis (TSA) was used to determine whether the present evidence was valid and conclusive for the primary outcomes. RESULTS: A total of seven randomized controlled trials involving 1,107 adult patients undergoing cardiac surgery fulfilled the inclusion criteria. The pooled analysis suggested that the use of fenoldopam was associated with a reduction in the incidence of AKI (18 of 216 [8.3%] in the fenoldopam group versus 45 of 222 [20.3%] in the placebo group, RR = 0.42 [0.26, 0.69], P = 0.0006) and with a higher rate of hypotension (92/357 [25.8%] versus 51/348 [14.7%], RR = 1.76 [1.29, 2.39], P = 0.0003). There was no significant effect on renal replacement therapy requirement (77 of 540 [14.3%] versus 75 of 536 [14.0%], P = 0.96) or hospital mortality (87/392 [22.2%] versus 83/383 [21.7%], P = 0.86). TSA supported the results of the conventional analysis on AKI. CONCLUSIONS: Low-dose dopamine offers transient improvements in renal physiology, but no good evidence shows that it offers important clinical benefits to patients with or at risk for acute renal failure.Among patients treated with fenoldopam, there was a decrease in AKI and an increased incidence of hypotension, had no significant effect on RRT or mortality. Given that most studies were small and the definition of AKI was variable between studies, there is not enough evidence to support the systematic use of fenoldopam in cardiac surgery.

Effects of Funneliformis mosseae on Root Metabolites and Rhizosphere Soil Properties to Continuously-Cropped Soybean in the Potted-Experiments.

Continuous cropping in soybean is increasingly practiced in Heilongjiang Province, leading to substantial yield reductions and quality degradation. Arbuscular mycorrhizal fungi (AMF) are soil microorganisms that form mutualistic interactions with plant roots and can restore the plant rhizosphere microenvironment. In this study, two soybean lines (HN48 and HN66) were chosen as experimental materials, which were planted in different years of continuous cropping soybean soils and were inoculated or not with Funneliformis mosseae in potted-experiments. Ultimately, analysis of root tissue metabolome and root exudates, soil physicochemical properties, plant biomass, as well as rhizosphere soil properties in different experimental treatments, inoculated or not with F. mosseae, was performed. Experimental results showed that: (a) The disease index of soybean root rot was significantly lower in the treatment group than in the control group, and there were differences in disease index and the resistance effect of F. mosseae between the two cultivars; (b) compared with the control, the root tissue metabolome and root exudates remained unchanged, but there were changes in the relative amounts in the treatment group, and the abundant metabolites differed by soybean cultivar; (c) soybean biomass was significantly higher in the treatment group than in the control group, and the effect of F. mosseae on biomass differed with respect to the soybean cultivar; and (d) there were differences in the physiochemical indexes of soybean rhizosphere soil between the treatment and control groups, and the repairing effect of F. mosseae differed between the two cultivars. Therefore, F. mosseae can increase the biomass of continuously cropped soybean, improve the physicochemical properties of the rhizosphere soil, regulate the root metabolite profiles, and alleviate barriers to continuous cropping in potted-experiments of soybean.

Reversible switching of magnetic states by electric fields in nitrogenized-divacancies graphene decorated by tungsten atoms.

Magnetic graphene-based materials have shown great potential for developing high-performance electronic devices at sub-nanometer such as spintronic data storage units. However, a significant reduction of power consumption and great improvement of structural stability are needed before they can be used for actual applications. Based on the first-principles calculations, here we demonstrate that the interaction between tungsten atoms and nitrogenized-divacancies (NDVs) in the hybrid W@NDV-graphene can lead to high stability and large magnetic anisotropy energy (MAE). More importantly, reversible switching between different magnetic states can be implemented by tuning the MAE under different electric fields, and very low energy is consumed during the switching. Such controllable switching of magnetic states is ascribed to the competition between the tensile stain and orbital magnetic anisotropy, which originates from the change in the occupation number of W-5d orbitals under the electric fields. Our results provide a promising avenue for developing high-density magnetic storage units or multi-state logical switching devices with ultralow power at sub-nanometer.

miR­494 is an independent prognostic factor and promotes cell migration and invasion in colorectal cancer by directly targeting PTEN.

Accumulating evidence has shown that micro-RNAs (miRNAs) are involved in multiple processes in cancer development and progression. Upregulation of miRNA-494 (miR-494) has been identified as an oncogenic miRNA and is associated with poor prognosis in several types of human cancer. However, the specific function of miR-494 in colorectal cancer remains unclear. In this study we found that the expression of miR-494 in colorectal cancer tissues and cell lines was much higher than in normal control tissues and cells, respectively. In addition, upregulation of miR-494 more frequently occurred in tissue specimens with adverse clinical stage and the presence of distant metastasis. Moreover, multivariate survival analyses demonstrated that overexpression of miR-494 is an independent prognostic factor for both progression-free and overall survival. In addition miR-494 promoted invasion and migration in colorectal cancer cells, and miR-494 directly inhibited the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression by targeting its 3'-untranslated region (3'-UTR). Moreover, PTEN is down regulated and inversely correlated with miR-494 expression in tissues. Thus, for the first time, we provided convincing evidence that upregulation of miR-494 was associated with tumor aggressiveness and tumor metastasis and promoted cell migration and invasion by targeting PTEN gene in colorectal cancer, and miR-494 is an independent prognostic marker for colorectal cancer patients.

Oxidative stress upregulates PDCD4 expression in patients with gastric cancer via miR-21.

Reactive oxygen species (ROS) plays a key role in carcinogenesis by aberrantly inducing signaling networks that initiatiate tumorigenesis and stimulate tumor progression. MicroRNAs (miRNAs) comprise a novel class of endogenous, small, noncoding RNAs that negatively regulate approximately 30% of the genes in a cell via degradation or translational inhibition of their target mRNAs. However, the effects of ROS on miRNAs expression and the role of miRNAs in ROS-mediated injury on carcinogenesis are uncertain. Using UV spectrophotometry and enzyme-linked immunosorbent assay (ELISA), we examined tissues from human gastric cancers and tissues adjascent to gastric cancer and normal gastric tissues and found that total anti-oxidation competence (T-AOC), superoxide dismutase (SOD) and catalase (CAT) concentrations were lower in gastric cancer patients compared to the control subjects, while the concentrations of DNA oxidative damage product 8-oxo-deoxyguanosine (8-OHdG) was higher. To determine the potential role of miRNA in gastric carcinogenesis, real-time quantitative polymerase chain reaction (QPCR) analysis was performed. We found that human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) mRNA and miR-21 expression were significantly upregulated in gastric cancer tissues than in the adjacent normal gastric tissues. Furthermore, the expression of programmed cell death 4 protein (PDCD4) in gastric cancer tissues was significantly lower than in adjacent normal gastric tissues. The expression of miR-21 and PDCD4 was highly correlated with the degree of differentiation, tumor staging, local lymphatic node metastasis and remote metastasis. Expression of miR-21 was negatively correlated with T-AOC, SOD and CAT, but positively correlated with 8-OHdG and hOGG1mRNA. In addition, the relative expression of PDCD4 was negatively correlated with miR-21. These results suggest that the defensive balance of oxidation and antioxidant system in patients with GC was impaired, resulting in enhanced oxidative tissue injury, which may directly contribute to gastric carcinogenesis. Thus we conclude that ROS promotes gastric carcinogenesis via upregulating miR-21 expression which in turn down-regulates the expression of PDCD4 in gastric cancer cells.

[Expressions of COX-2, PKC-α and miR-101 in gastric cancer and their correlations].

OBJECTIVE: To investigate the expressions of miR-101, protein kinase C-α (PKC-α), and cyclooxygenase-2 (COX-2) in gastric cancer (GC) tissue and their correlations. METHODS: RT-qPCR was used to examine miR-101 expression and Western blotting employed to detect PKC-α and COX-2 expressions in 57 cases of gastric cancer tissues and paired normal gastric mucosal tissues. RESULTS: The gastric cancer tissues showed a significantly lower miR-101 expression (Z=6.102, P<0.05) but significantly higher expressions of COX-2 (Z=14.436, P<0.05) and PKC-α (Z=6.955, P<0.05) than the normal gastric tissues. The expression of COX-2 protein was significantly correlated with the degree of differentiation, invasion depth, lymph node metastasis and TNM stage (P<0.05); PKC-α protein expression was associated with lymph node metastasis and TNM stage (P<0.05). PKC-α expression was positively correlated (r=0.531, P<0.05) and miR-101 expression negatively correlated (r=-0.627, P<0.05) with COX-2 expression in gastric cancer tissues. CONCLUSIONS: miR-101, PKC-α and COX-2 all play a role in the tumorigenesis and progression of gastric cancer. miR-101 and PKC-α might be new potential therapeutic targets for inhibiting COX-2 in gastric cancer.

Angiotensin II receptor type 1 blockers suppress the cell proliferation effects of angiotensin II in breast cancer cells by inhibiting AT1R signaling.

Chronic stress and a high-fat diet are well-documented risk factors associated with the renin-angiotensin system in the development of breast cancer. The angiotensin II type 1 receptor (AT1R) is a novel component of the renin-angiotensin system. Several recent studies have focused on the function of AT1R in cell proliferation during cancer development. Thus, we hypothesized that angiotensin II (Ang Ⅱ) can promote proliferation of breast cancer via activated AT1R; the activation of AT1R may play an important role in promoting breast cancer growth, and AT1R blocker (ARB) may suppress the promotional effect on proliferation by antagonizing AT1R. The expression level of AT1R was found to be significantly upregulated in breast cancer cells by immunohistochemistry, but no correlation between AT1R expression and ER/PR/Her-2 expression was observed. The AT1R(+)-MCF-7 cell line exhibited high expression of AT1R protein, and we generated the AT1R(-)-MCF-7 cell line using RNA interference. ARBs, and in particular irbesartan, effectively inhibited the effects of Ang II on cell proliferation, cell cycle development and downstream AT1R signaling events, including the activation of the Ras-Raf-MAPK pathway and the transcription factors NF-κB and CREB. Irbesartan also significantly altered p53, PCNA and cyclin D1 expression, which was also influenced by activated AT1R in AT1R(+)-MCF-7 cells. These results suggest that ARBs may be useful as a novel preventive and therapeutic strategy for treating breast cancer.

[Role of oxidative stress and thioredoxin in gastric cancer].

OBJECTIVE: To explore the role of oxidative stress and the antioxidant protein thioredoxin in the tumorigenesis and progression of gastric cancer. METHODS: The plasma levels of adenosine deaminase (ADA), glutathione peroxidase (GPX), superoxide dismutase (SOD), and advanced oxidation protein products (AOPP) were determined by colorimetry, and the plasma levels of thioredoxin were determined by enzyme-linked immunosorbent assay (ELISA) in 48 gastric cancer patients and 30 healthy subjects. RT-PCR assay was employed to examine the expression levels of thioredoxin mRNA in the tissue samples of the patients. RESULTS: Compared with the healthy controls, patients with gastric cancer had significantly increased plasma levels of ADA and AOPP (P<0.05), decreased plasma GPX level (P<0.05), and similar plasma SOD levels. The plasma levels of thioredoxin were significantly higher in patients with gastric cancer than in the healthy controls (P<0.05). Thioredoxin levels was not associated with gender, age, degree of tumor cell differentiation, invasion depth, or lymph node metastasis (P>0.05), but was correlated to distant tumor metastasis (P<0.05). The expression of Trx mRNA was significantly higher in gastric carcinoma than in normal gastric tissue (P<0.05). CONCLUSION: Gastric cancer patients have high levels of oxidative stress and thioredoxin expression, and the latter is related to distant metastasis of the tumor.