Comparative Analysis on the Duodenal Microbiota Community in Geese Fed with the All-grass or Basal Diet

Geese (Anser cygnoides) possess stronger ability of roughage digestion and utilization than other poultries, hence, it has become the focus of attention of scientists. Duodenal, jejunum and ileum were mainly participated in food digestion and nutrient absorption, while the cecum was responsible for biological fermentation. Effects on the geese's cecal microbiota community by feeding with the all-grass diet have been investigated, however, whether it had an influence on the geese's duodenal microbiota community remains unexplored. To address this problem, geese feeding with the basal diet for 28 days (G1), the basal diet for 28 days and the all-grass diet for the following 14 days (G2), the basal diet for 42 days (G3) were selected, respectively. The duodenal segments of geese were collected and the hypervariable V3-V4 region of the bacterial 16S rRNA gene was sequencing. A total of 4 main phyla and 16 main genera were identified. Moreover, we also successfully identified that two taxa including the Helcococcus and Clostridium could be used as distinguishing biomarkers specific to G2. The functional profiles of the duodenum microbiota were mainly involved in the membrane transport (e.g. ABC transporters), amino acid metabolism, energy metabolism, metabolism of cofactors and vitamins, and cellular processes and signaling pathways in geese feeding with the all-grass diet. In conclusion, the all-grass diet could impact the composition of duodenal microbiota. However, to resolve the underlying mechanism of the fiber digesting and utilization in geese's gut microbiota, the whole intestinal system needs to be assessed by further studies.(AU)

Enhanced anticancer activity and endocytic mechanisms by polymeric nanocarriers of n-butylidenephthalide in leukemia cells.

PURPOSE: The purpose of this study was to investigate the antitumor mechanisms of n-butylidenephthalide (BP) and to further examine the delivery efficacy of polycationic liposome containing PEI and polyethylene glycol complex (LPPC)-encapsulated BP in leukemia cells. METHODS: MTS, flow cytometric and TUNEL assays were performed to assess cell viability and apoptosis. BP and BP/LPPC complex delivery efficiency was analyzed by full-wavelength fluorescent scanner and fluorescence microscope. The expressions of cell cycle- and apoptosis-related proteins were conducted by Western blotting. RESULTS: The results showed that BP inhibited leukemia cell growth by inducing cell cycle arrest and cell apoptosis. LPPC-encapsulated BP rapidly induced endocytic pathway activation, resulting in the internalization of BP into leukemia cells, causing cell apoptosis within 1 h. CONCLUSIONS: LPPC encapsulation enhanced the cytotoxic activity of BP and did not influence the effects of BP induction that suggested LPPC-encapsulated BP might be developed as anti-leukemia drugs in future.

Research progress of tumor microenvironment and tumor-associated macrophages.

Cancer is a health issue causing utmost concern and continuing to be one of the leading causes of mortality worldwide. Effective tumor eradication methods that will improve the prognosis and prolong human life are an important topic in modern medicine. Increasing amounts of evidence indicate that the tumor microenvironment plays a significant role in tumor development and migration. Macrophages are important immune cells that commonly infiltrate the tumor microenvironment. Several studies found that macrophages play different roles in the process of cancer development. This article focuses on the tumor microenvironment and the generation, classification, and function of tumor-associated macrophages as well as their significance for tumor immunotherapy and other aspects, it summarizes nearly 10 years of tumor microenvironment and tumor-associated macrophage research, providing a novel insight for tumor immunotherapy.

Orphan nuclear receptor COUP-TFII is an oncogenic gene in renal cell carcinoma.

BACKGROUND: Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) may be an oncogenic gene in renal cell carcinoma (RCC). However, the direct association between COUP-TFII expression and patient survival has not been investigated in patients with RCC, and the molecular oncogenesis of COUP-TFII in RCC remains unclear. METHODS: The mRNA expression levels of COUP-TFII in the tumors of 283 patients with RCC were determined by RT-qPCR. The remaining 266 patients were categorized into low- and high-expression groups according to the cut off value generated by receiver operating curve (ROC) analysis. The function of COUP-TFII in RCC cells was tested by knockdown experiments in vitro. RESULTS: In the present study, it was revealed that the mRNA expression levels of COUP-TFII were significantly higher in tumors compared with those in adjacent non-cancerous tissues, and that the overexpression of COUP-TFII was strongly associated with poor patient survival. It was further demonstrated that knockdown of COUP-TFII suppressed proliferation, and induced apoptosis and cell cycle arrest in RCC cells in vitro. This also resulted in the activation of the mitochondria-mediated apoptosis pathway, impaired migration and invasion of RCC cells through epithelial-mesenchymal transition in vitro, and suppressed tumor growth in vivo. In addition, it was revealed that the induction of cell migration and invasion by COUP-TFII was mediated, at least in part, by integrin subunit ß1. CONCLUSIONS: In summary, the present study indicated that COUP-TFII is an oncogenic gene in RCC, and a potential therapeutic target for the treatment of the disease.

Intraoperative blood loss does not independently affect the survival outcome of gastric cancer patients who underwent curative resection.

BACKGROUND: Whether intraoperative blood loss (IBL) was independently associated with poor prognosis of gastric cancer (GC) patients remains controversial. In the present study, we evaluated the impact of IBL on the disease-free survival (DFS) of GC patients. METHODS: A total of 1669 patients who underwent curative gastrectomy for GC were reviewed retrospectively. All patients were classified as IBL < 400 mL and IBL ≥ 400 mL group according to the amount of IBL. The prognostic difference between two patient groups was compared and clinicopathologic factors associated with the prognosis of GC patients were analyzed. RESULTS: The 5-year DFS rate of the patients with IBL < 400 mL and those with IBL ≥ 400 mL was 52.1% and 41.5%, respectively (P < 0.001). The 5-year DFS rate of the patients who did and did not receive intraoperative blood transfusion was 36.9% and 53.2%, respectively (P < 0.001). However, the similar survival outcomes were not observed in the subgroup analysis based on the TNM stage. The multivariate analysis indicated that IBL (HR 1.021, 95% CI 0.875-1.191, P > 0.05) and intraoperative blood transfusion (HR 1.111, 95% CI 0.943-1.309, P > 0.05) were not independent prognostic factors for GC patients. In addition, the patients with IBL ≥ 400 mL had a higher risk of postoperative complications than those with IBL < 400 mL, especially for intraabdominal infection and wound infection. The tumor located in upper 1/3 stomach, total gastrectomy, combined organ resection and advanced tumor stage (stage III) were independent risk factors for intraoperative massive hemorrhage. CONCLUSION: Intraoperative blood loss was significantly associated with tumor-related and surgery-related factors. Intraoperative blood loss itself could not independently affect survival outcome of GC patients after curative gastrectomy.

The effects of threonine on performance parameters, carcass traits, visceral organ indices and serum biochemical parameters of Linwu ducks, aged 4 to 8 weeks

This study was conducted to establish dietary threonine (Thr) levels for Linwu ducks, aged 4 to 8 wk. Experimental diets formulated to contain 0.56, 0.61, 0.66, 0.71, 0.76, and 0.81% Thr fed to Linwu ducks. A total of 360 healthy Linwu female ducks with similar body weight (1183.89±3.83 g) were randomly divided into six groups, with five replicates in each group, and 12 ducks in each replicate. Samples were collected at 8 wk for the determination of growth performance, carcass traits, visceral organ indices, and serum biochemical parameters. As a result of this study, Thr level had no significant influence on the final weight, the daily gain, feed/gain ratio, and average daily intake (p>0.05). Similarly, there were no significant effects of dietary Thr on carcass traits and visceral organ indices (p>0.05). The pancreatic index was highest among all the treatments when the dietary Thr level was 0.66%. The different dietary Thr levels had no significant effect (p>0.05) on the concentration of total protein (TP), triglyceride (TG), total cholesterol (TC), glucose (GLU), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and glutathione (GSH). However, the serum MDA concentration in the 0.66% treatment was lower (P=0.068) than in the other treatments. In conclusion, Thr at 0.66% concentration may have an antioxidant activity and exert positive effect on Linwu ducks.(AU)

The effects of threonine on performance parameters, carcass traits, visceral organ indices and serum biochemical parameters of Linwu ducks, aged 4 to 8 weeks

This study was conducted to establish dietary threonine (Thr) levels for Linwu ducks, aged 4 to 8 wk. Experimental diets formulated to contain 0.56, 0.61, 0.66, 0.71, 0.76, and 0.81% Thr fed to Linwu ducks. A total of 360 healthy Linwu female ducks with similar body weight (1183.89±3.83 g) were randomly divided into six groups, with five replicates in each group, and 12 ducks in each replicate. Samples were collected at 8 wk for the determination of growth performance, carcass traits, visceral organ indices, and serum biochemical parameters. As a result of this study, Thr level had no significant influence on the final weight, the daily gain, feed/gain ratio, and average daily intake (p>0.05). Similarly, there were no significant effects of dietary Thr on carcass traits and visceral organ indices (p>0.05). The pancreatic index was highest among all the treatments when the dietary Thr level was 0.66%. The different dietary Thr levels had no significant effect (p>0.05) on the concentration of total protein (TP), triglyceride (TG), total cholesterol (TC), glucose (GLU), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and glutathione (GSH). However, the serum MDA concentration in the 0.66% treatment was lower (P=0.068) than in the other treatments. In conclusion, Thr at 0.66% concentration may have an antioxidant activity and exert positive effect on Linwu ducks.

Comparative study of 13 candidate genes applying multi-reference normalization to detect the expression of different fineness in skin tissues of wool sheep.

Fiber diameter is a useful indicator of wool traits and it is the main determinant of wool quality and value. A comparative study was conducted to analyze the abundance and expression of 13 candidate genes using expression profile microarray analysis and to identify novel molecular markers associated with wool traits to provide a molecular basis for improving wool quality in sheep. Genes associated with fineness of skin tissue were identified using a real-time reverse transcriptase-polymerase chain reaction method with 18SrRNA, ß-Actin, and GAPDH used for multi-reference normalization. The results indicated that the expression levels of TXNIP, TFDP1, and FAIM genes in super-fine type wool sheep were higher than those in fine-type wool sheep; the corresponding expression ratios of super-fine to fine wool sheep were 1.45, 1.57, and 2.55, respectively. The expression levels of PIK3CA, ADAM9, and FZD3 genes were lower in super-fine wool sheep compared with fine-type wool sheep; the corresponding expression ratios were 0.61, 0.65, and 0.52, respectively. The other genes tested (RPS6KA, ABCG2, GSTA1, PTPN13, GJB3, PPARD, and LAMB1) were similarly expressed in both types of wool sheep. These results infer that lower expression of PIK3CA, ADAM9, and FZD3 genes was associated with lower fiber diameter, whereas lower expression of TXNIP, TFDP1, and FAIM genes was associated with higher fiber diameter.

Propofol inhibits invasion and growth of ovarian cancer cells via regulating miR-9/NF-κB signal.

Propofol is one of the most commonly used intravenous anesthetic agents during cancer resection surgery. A previous study has found that propofol can inhibit invasion and induce apoptosis of ovarian cancer cells. However, the underlying mechanisms are not known. miR-9 has been reported to be little expressed in ovarian cancer cells, which has been related to a poor prognosis in patients with ovarian cancer. Studies have also demonstrated that propofol could induce microRNAs expression and suppress NF-κB activation in some situations. In the present study, we assessed whether propofol inhibits invasion and induces apoptosis of ovarian cancer cells by miR-9/NF-κB signaling. Ovarian cancer ES-2 cells were transfected with anti-miR-9 or p65 cDNA or p65 siRNA for 24 h, after which the cells were treated with different concentrations of propofol (1, 5, and 10 µg/mL) for 24 h. Cell growth and apoptosis were detected using MTT assay and flow cytometry analysis. Cell migration and invasion were detected using Transwell and Wound-healing assay. Western blot and electrophoretic mobility shift assay were used to detect different protein expression and NF-κB activity. Propofol inhibited cell growth and invasion, and induced cell apoptosis in a dose-dependent manner, which was accompanied by miR-9 activation and NF-κB inactivation. Knockdown of miR-9 abrogated propofol-induced NF-κB activation and MMP-9 expression, reversed propofol-induced cell death and invasion of ES-2 cells. Knockdown of p65 inhibited NF-κB activation rescued the miR-9-induced down-regulation of MMP-9. In addition, overexpression of p65 by p65 cDNA transfection increased propofol-induced NF-κB activation and reversed propofol-induced down-regulation of MMP-9. Propofol upregulates miR-9 expression and inhibits NF-κB activation and its downstream MMP-9 expression, leading to the inhibition of cell growth and invasion of ES-2 cells.

Orthogonal design in the optimization of a start codon targeted (SCoT) PCR system in Roegneria kamoji Ohwi.

Roegneria kamoji Ohwi is an excellent forage grass due to its high feeding value and high resistance to some biotic and abiotic stresses. However, the start codon targeted (SCoT) polymorphism has not been conducted on R. kamoji. In this study, an orthogonal L16 (45) design was employed to investigate the effects of five factors (Mg2+, dNTPs, Taq DNA polymerase, primer, and template DNA) on the polymerase chain reaction (PCR) to determine the optimal SCoT-PCR system for R. kamoji. The results showed that the most suitable conditions for SCoT-PCR in R. kamoji included 1.5 mM Mg2+, 0.15 mM dNTPs, 1.0 U Taq DNA polymerase, 0.4 pM primer, and 40 ng template DNA. SCoT primers 39 and 41 were used to verify the stability of the optimal reaction system, and amplification bands obtained from diverse samples were found to be clear, rich, and stable in polymorphisms, indicating that this reaction system can be used for SCoT-PCR analysis of R. kamoji. We have developed a simple and rapid way to study the mutual effects of factors and to obtain positive results through the use of an orthogonal design L16 (45) to optimize the SCoT-PCR system. This method may provide basic information for molecular marker-assisted breeding and analyses of genetic diversity in R. kamoji.

Genetic association of sequence variation in exon 3 of the swine leukocyte antigen-DQA gene with piglet diarrhea in Large White, Landrace, and Duroc piglets.

Piglet diarrhea is one of the primary factors that affects the benefits of the swine industry. Recent studies have shown that exon 2 of the swine leukocyte antigen-DQA gene is associated with piglet resistance to diarrhea; however, the contributions of additional exon coding regions of this gene remain unclear. Here, we detected and sequenced variants in the exon 3 region and examined their associations with diarrhea infection in 425 suckling piglets using the polymerase chain reaction-single-strand conformational polymorphism and sequencing analysis. The results revealed that exon 3 of the swine leukocyte antigen-DQA gene is highly polymorphic and pivotal to both diarrhea susceptibility and resistance in piglets. We identified 14 genotypes (AA, AB, BB, BC, CC, EE, EF, BE, BF, CF, DD, DH, GG, and GF) and eight alleles (A-H) that were generated by 14 nucleotide variants, eight of which were novel, and three nucleotide deletions. Statistical analyses revealed that the genotypes AB and EF were associated with resistance to diarrheal disease (P < 0.05), and the genotype DD may contribute to diarrhea susceptibility but was unique to Large White pigs (P > 0.05). These results elucidate the genetic and immunological background to piglet diarrhea, and provide useful information for resistance breeding programs.

Detection of quantitative trait loci for kernel oil and protein concentration in a B73 and Zheng58 maize cross.

Maize (Zea mays L.) is one of the most important food crops throughout the world, and provides oil and proteins to humans and livestock. Kernel oil and protein content in maize are two complex quantitative traits. In order to identify quantitative trait loci (QTL) controlling oil and protein concentration in maize kernels, and to evaluate their genetic effects, QTL analysis was conducted on an F3:4 population derived from a cross between an inbred line with a low oil and protein concentration (Zheng58) and an inbred line with a higher oil and protein concentration (B73). A total of 189 polymorphic simple sequence repeat markers were used to construct a linkage map. Eleven QTLs for kernel oil concentration were detected on nine chromosomes, except for chromosome 9. A single QTL explained 4.6 to 11.1% of the phenotypic variance. Ten QTLs for kernel protein concentration were also detected on nine chromosomes, except for chromosome 9. A single QTL explained 4.2 to 11.4% of the phenotypic variance. Interestingly, novel QTLs for oil concentration (qOIL08-01 and qOIL10-01) and QTLs for protein concentration (qPRO01-01 and qPRO05-01) were specific to the population studied, which could explain 7.1 to 11.1% of the phenotypic variance. These results will provide better understanding of the genetic basis of oil and protein concentrations in maize. The markers closely linked with the QTLs will facilitate breeding of maize varieties with high oil and protein concentrations through molecular marker-assisted selection.

Association between IL-17A and IL-17F gene polymorphisms and risk of gastric cancer in a Chinese population.

We conducted a case-control study to investigate the role of interleukin-17A (IL-17A) rs2275913 G > A and IL-17F rs763780 T > C polymorphisms in the development of gastric cancer. A hospital-based case-control design was performed, and 153 patients and 207 control subjects were consecutively selected from the Third Affiliated Hospital between May 2013 and December 2014. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype for IL-17A rs2275913 G > A and IL-17F rs763780 T > C. The genotypes of IL-17A rs2275913 G > A and IL-17F rs763780 T > C did not deviate from Hardy-Weinberg equilibrium (P values were 0.44 and 0.11, respectively). By unconditional logistic regression analysis, we observed that the GG genotype of rs2275913 was associated with an increased risk of gastric cancer compared to the AA genotype [odds ratio (OR) = 2.66; 95% confidence interval (CI) = 1.26-5.66]. The AG + GG genotype of rs2275913 increased the susceptibility to gastric cancer compared to the AA genotype, and the adjusted OR (95%CI) was 2.66 (1.26-5.66). Moreover, the GG genotype of rs2275913 was correlated with an elevated risk of gastric cancer when compared with the AA + AG genotype (OR = 2.15; 95%CI = 1.08-4.34). In conclusion, we found that the IL-17A rs2275913 G > A gene polymorphism was significantly associated with an increased risk of gastric cancer in co-dominant, dominant, and recessive models.

Whole-transcriptome sequencing of Pinellia ternata using the Illumina platform.

Pinelliae rhizoma is the dried tuber of Pinellia ternata (Thunb.) Breit., and has been used for thousands of years as a traditional Chinese medicine. However, its genomic background is little known. With the development of high-throughput genomic sequencing, it is now easy and cheap to obtain genomic information. In this study, 193,032,910 high-quality clean reads were generated using the Illumina Hiseq 2000 platform. A total of 53,544 unigenes were identified from the contigs assembled. Functional annotation analysis annotated 37,318, 27,697, 23,043, 22,869, 23,328, and 27,415 unigenes. KEGG analysis revealed that five pathways (169 genes) were associated with alkaloid synthesis, 201 unigenes were related to fatty acid biosynthesis (ko00061), and 133 unigenes were involved in the biosynthesis of unsaturated fatty acids (ko01040). In addition, 6703 simple sequence repeats were designed based on the unigene sequences for screening germplasm resources in the future. These data are a valuable resource for genomic studies on Pinellia plants.

Identification of robust adaptation gene regulatory network parameters using an improved particle swarm optimization algorithm.

Robust adaptation is a critical ability of gene regulatory network (GRN) to survive in a fluctuating environment, which represents the system responding to an input stimulus rapidly and then returning to its pre-stimulus steady state timely. In this paper, the GRN is modeled using the Michaelis-Menten rate equations, which are highly nonlinear differential equations containing 12 undetermined parameters. The robust adaption is quantitatively described by two conflicting indices. To identify the parameter sets in order to confer the GRNs with robust adaptation is a multi-variable, multi-objective, and multi-peak optimization problem, which is difficult to acquire satisfactory solutions especially high-quality solutions. A new best-neighbor particle swarm optimization algorithm is proposed to implement this task. The proposed algorithm employs a Latin hypercube sampling method to generate the initial population. The particle crossover operation and elitist preservation strategy are also used in the proposed algorithm. The simulation results revealed that the proposed algorithm could identify multiple solutions in one time running. Moreover, it demonstrated a superior performance as compared to the previous methods in the sense of detecting more high-quality solutions within an acceptable time. The proposed methodology, owing to its universality and simplicity, is useful for providing the guidance to design GRN with superior robust adaptation.

Relationship between the expression of Notch1 and EZH2 and the prognosis of breast invasive ductal carcinoma.

We determined whether the coexpression of Notch1 and EZH2 influences the progression and prognosis of breast invasive ductal carcinoma. Using the χ(2) test, a significant difference was found between high and low expression of Notch1 in terms of lymph node, hormone receptor, and p53 expression (P < 0.05). Moreover, a significant difference was found between high and low expression of EZH2 in terms of tumor size, histologic grade, hormone receptor, and expression of Ki67 (P < 0.05). Using Pearson correlation analysis, we found a significant positive correlation between Notch1 and EZH2 expression in the tissue samples of breast invasive ductal carcinoma (P = 0.038). High Notch1 and EZH2 expression was associated with poor progression-free survival compared with low expression (PNotch1 = 0.000, 40.3 vs 48.9 months; PEZH2 = 0.000, 40.2 vs 49.9 months). Moreover, we found that high Notch1 and EZH2 expression was associated with poor overall survival compared with low expression (PNotch1 = 0.000, 51.2 vs 56.2 months; PEZH2 = 0.002, 51.7 vs 56.4 months). In conclusion, Notch1 and EZH2 coexpression contributes to the progression and prognosis of breast invasive ductal carcinoma.

Vasculogenic mimicry and hypoxia-inducible factor-1α expression in cervical squamous cell carcinoma.

In this study, the existence of vasculogenic mimicry (VM) in cervical squamous cell carcinoma was investigated. To this end, the relationship between hypoxia-inducible factor 1α (HIF-1α) and the development, infiltration, and metastasis of cervical squamous cell carcinoma was studied. Between January 2010 and December 2010, 67 human cervical squamous carcinoma tissue samples were collected and stained by CD34/periodic acid-Schiff double staining to detect the existence of VM. HIF-1α expression was analyzed by immunohistochemistry. The relationship between VM and HIF-1α was also analyzed. Normal cervical tissues (20 cases) from patients who had uterine surgeries in the same period were collected as controls. In the cervical squamous carcinoma tissues, positive rates of VM and HIF-1α were 38.81% (26/67) and 64.18% (43/67), respectively. This was significantly higher than those in the normal cervical tissues [0 (0/20); P < 0.05]. VM rates in cervical squamous carcinoma tissues from patients with different pathological grades, Federation of Gynecology and Obstetrics (FIGO) stages, and lymph node metastasis states were also significantly different (P < 0.05). In addition, significant differences in HIF-1α positivity rates were observed among patients with varying tumor sizes and lymph node metastasis states (P < 0.05). Positive correlation was found between VM and HIF-1α (r = 0.339, P < 0.05). To summarize, we found VM in cervical squamous carcinoma; high expression of HIF-1α may promote VM formation, as well as cervical squamous cell infiltration and metastasis.

Paclitaxel induces apoptosis in leukemia cells through a JNK activation-dependent pathway.

Paclitaxel (PTX) is a mitotic inhibitor widely used in chemotherapy for many types of cancers, including solid tumors and hematological malignancies. However, the molecular basis of the anti-proliferation activity of PTX is not fully understood. In this paper, we focused on the role of c-Jun N-terminal kinase (JNK) pathways in PTX-induced apoptosis and proliferation inhibition. The effects of PTX were examined in human leukemia cell lines and patients' chronic lymphocytic leukemia (CLL) cells in relation to mitochondrial events, apoptosis, and perturbation of JNK activation using flow cytometry, siRNA, mitochondrial membrane potential determination, and western blotting. Exposure of cells to PTX at concentrations ≥ 10 nM for 18 or 24 h resulted in a significant release of cytochrome c from mitochondria to the cytosol, cleavages of procaspase 3 and poly (ADP-ribose) polymerase (PARP), and JNK activation, leading to apoptosis. The pan-caspase inhibitor BOC-D-FMK blocked the PTX-induced apoptosis but had no effect on cytochrome c release, suggesting that cytochrome c had been released before caspase activation. Moreover, both pharmacological JNK inhibitors SP600125 and JNK siRNA dramatically blocked PTX-induced apoptosis, cytochrome c release, caspase 3, and PARP cleavage. These findings demonstrate that JNK activation plays a critical role in the induction of apoptosis mediated by PTX in human leukemia cell lines and CLL patient-derived primary cancer cells, and this event is upstream of cytochrome c release, caspase 3, and PARP cleavage.

A functional insertion/deletion polymorphism in the IL1A gene is associated with decreased risk of breast cancer.

The insertion/deletion polymorphism (rs3783553 TTCA/-) in the 3' untranslated region of interleukin-1A (IL1A) has been studied intensively and has been shown to affect tumor risk. We studied the frequency of the IL1A gene polymorphism rs3783553 and evaluated its relationship with breast cancer (BC). A hospital-based case-control study comprising 228 patients with histologically confirmed BC and 241 healthy subjects was conducted. Polymerase chain reaction was used to detect the IL1A rs3783553 polymorphism. The ins/ins (ttca/ttca) genotype was significantly associated with a decreased risk of BC compared with the del/del (-/-) genotype (OR = 0.48, 95% CI = 0.27-0.85). Moreover, the ins (ttca) allele distribution between cases and controls was significantly different from the del (-) allele distribution (OR = 0.74, 95% CI = 0.57-0.96). Thus, the rs3783553 polymorphism is associated with a decreased incidence of breast cancer.

Propofol inhibits invasion and growth of ovarian cancer cells via regulating miR-9/NF-kappaB signal

Propofol is one of the most commonly used intravenous anesthetic agents during cancer resection surgery. A previous study has found that propofol can inhibit invasion and induce apoptosis of ovarian cancer cells. However, the underlying mechanisms are not known. miR-9 has been reported to be little expressed in ovarian cancer cells, which has been related to a poor prognosis in patients with ovarian cancer. Studies have also demonstrated that propofol could induce microRNAs expression and suppress NF-κB activation in some situations. In the present study, we assessed whether propofol inhibits invasion and induces apoptosis of ovarian cancer cells by miR-9/NF-κB signaling. Ovarian cancer ES-2 cells were transfected with anti-miR-9 or p65 cDNA or p65 siRNA for 24 h, after which the cells were treated with different concentrations of propofol (1, 5, and 10 μg/mL) for 24 h. Cell growth and apoptosis were detected using MTT assay and flow cytometry analysis. Cell migration and invasion were detected using Transwell and Wound-healing assay. Western blot and electrophoretic mobility shift assay were used to detect different protein expression and NF-κB activity. Propofol inhibited cell growth and invasion, and induced cell apoptosis in a dose-dependent manner, which was accompanied by miR-9 activation and NF-κB inactivation. Knockdown of miR-9 abrogated propofol-induced NF-κB activation and MMP-9 expression, reversed propofol-induced cell death and invasion of ES-2 cells. Knockdown of p65 inhibited NF-κB activation rescued the miR-9-induced down-regulation of MMP-9. In addition, overexpression of p65 by p65 cDNA transfection increased propofol-induced NF-κB activation and reversed propofol-induced down-regulation of MMP-9. Propofol upregulates miR-9 expression and inhibits NF-κB activation and its downstream MMP-9 expression, leading to the inhibition of cell growth and invasion of ES-2 cells.