An esculentin-1 homolog from a dark-spotted frog (Pelophylax nigromaculatus) possesses antibacterial and immunoregulatory properties.

BACKGROUND: Esculentin-1, initially discovered in the skin secretions of pool frogs (Pelophylax lessonae), has demonstrated broad-spectrum antimicrobial activity; however, its immunomodulatory properties have received little attention. RESULTS: In the present study, esculentin-1 cDNA was identified by analysing the skin transcriptome of the dark-spotted frog (Pelophylax nigromaculatus). Esculentin-1 from this species (esculentin-1PN) encompasses a signal peptide, an acidic spacer peptide, and a mature peptide. Sequence alignments with other amphibian esculentins-1 demonstrated conservation of the peptide, and phylogenetic tree analysis revealed its closest genetic affinity to esculentin-1P, derived from the Fukien gold-striped pond frog (Pelophylax fukienensis). Esculentin-1PN transcripts were observed in various tissues, with the skin exhibiting the highest mRNA levels. Synthetic esculentin-1PN demonstrated antibacterial activity against various pathogens, and esculentin-1PN exhibited bactericidal activity by disrupting cell membrane integrity and hydrolyzing genomic DNA. Esculentin-1PN did not stimulate chemotaxis in RAW264.7, a murine leukemic monocyte/macrophage cell line. However, it amplified the respiratory burst and augmented the pro-inflammatory cytokine gene (TNF-α and IL-1ß) expression in RAW264.7 cells. CONCLUSIONS: This novel finding highlights the immunomodulatory activity of esculentin-1PN on immune cells.

EDIII-Fc induces protective immune responses against the Zika virus in mice and rhesus macaque.

Zika virus can infect the fetus through the placental barrier, causing ZIKV congenital syndrome and even miscarriage, which can cause great harm to pregnant women and infants. Currently, there is no vaccine and drug available to combat the Zika virus. In this study, we designed a fusion protein named EDIII-Fc, including the EDIII region of Zika E protein and human IgG Fc fragment, and obtained 293T cells that stably secreted EDIII-Fc protein using the lentiviral expression system. Mice were immunized with the EDIII-Fc protein, and it was observed that viral replication was significantly inhibited in the immunized mice compared to non-immunized mice. In rhesus macaques, we found that EDIII-Fc effectively induce the secretion of neutralizing antibodies and T cell immunity. These experimental data provide valid data for further use of Zika virus E protein to prepare an effective, safe, affordable Zika vaccine.

In situ effects of microplastics on the decomposition of aquatic macrophyte litter in eutrophic shallow lake sediments, China.

The toxicity of microplastics (MPs) to aquatic organisms has been extensively studied recently. However, few studies have investigated the effects of MPs in sediments on aquatic ecosystem functioning. In the present study, we conducted an in situ experiment to explore the concentration-dependent effects (0.025%, 0.25%, 2.5%) and size-dependent effects (150-300 µm and 500-1000 µm) of polypropylene microplastics (PP MPs) on Vallisneria natans litter decomposition dynamics, in particular, the process associated with macroinvertebrates, microorganisms, as well as microalgae and/or cyanobacteria. The results showed that exposure to high concentrations and large sizes of PP MPs can accelerate leaf litter biomass loss and nutrition release. Moreover, microbial respiration, microalgal and/or cyanobacteria chlorophyll-a were also significantly affected by PP MPs. However, PP MPs have no effect on the abundance of associated macroinvertebrate during the experiment, despite the collection of five macroinvertebrate taxa from two functional feeding groups (i.e., collectors and scrapers). Therefore, our experiment demonstrated that PP MPs may enhance leaf litter decomposition through effected microbial metabolic activity, microalgal and/or cyanobacteria biomass in the sedimentary lake. Overall, our findings highlight that PP MPs have the potential to interfere with the basic ecological functions such as plant litter decomposition in aquatic environments.

Luteolin improves vasoconstriction function and survival of septic mice via AMPK/NF-κB pathway.

Septic shock, the leading cause of death in sepsis, is related to vasoconstriction dysfunction. To investigate the effects of Luteolin (LTL), a flavonoid polyphenol compound, on vasoconstriction dysfunction in septic mice and the underlying mechanism, cecal ligation and puncture (CLP) surgery was performed on wild-type C57BL/6 mice to induce septic shock. Mice were intraperitoneally injected with 0.2 mg/kg LTL within 10 min after CLP surgery with or without 20 mg/kg Compound C (AMPK inhibitor) (CC) 1 h before CLP surgery, and re-administrated every 12 h. The survival rate, systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) were explored. After the mice were sacrificed, the vasoconstriction function, inflammatory indicators, and possible regulatory signaling pathways were examined. Our data showed that CLP decreased the survival rate, SAP, DAP, MAP, vasoconstriction function, and expression of ADRA1A and p-AMPK/AMPK, as well as increased the mRNA expression of inflammatory cytokines and iNOS, the serum levels of inflammatory cytokines, and the levels of iNOS, p-p65/p65, and p-IκBα/IκBα in aortas (P < 0.05), which could be reversed by LTL treatment (P < 0.05). However, inhibition of AMPK could abolish the protective effects of LTL (P < 0.05). In conclusion, our study manifested that LTL could prevent vasoconstriction dysfunction and increase survival of septic mice via activating AMPK, which suggested that LTL could be a novel therapeutic option for patients with sepsis.

Exo-III Enzyme and DNAzyme-Assisted Dual Signal Recycles for Sensitive Analysis of Exosomes by Using Personal Glucose Meter.

Exosome plays a crucial role in regulating intercellular communication during atherosclerosis development. However, sensitive and portable exosome detection remains a huge challenge. Herein, a personal glucose meter (PGM)-based exosomes detection approach has been proposed that allows detection of exosomes with a high sensitivity and reproducibility. In this method, a catch probe, which is composed of CD63 aptamer and blocker sequence, is utilized for the specific identification of exosomes. The blocker sequence binds with H probe to initiate the Exo-III-assisted signal recycles to generate numerous DNAzyme sequences. Under the assistance of the substrate, DNAzyme forms its active secondary structure to generate gap site in substrate, releasing a linker to conjugate sucrase to streptavidin magnetic beads (SMBs). After removing unbound sucrase, the SMB-linker-sucrase complex is used to catalyze sucrose to glucose, which can be read by PGMs. Based on this, the method exhibits a wide detection range and a low limit of detection, holding a promising prospect for the analysis of exosomes and screening atherosclerosis.

Effect of Ultrasonic Pretreatment on Flocculation Filtration of Low-Rank Coal Slurry.

The efficient filtration of low-rank coal (LRC) slurry was significantly beneficial to the production process of wet coal beneficiation. However, relatively few studies have been reported on novel pretreatment methods for the efficient filtration of LRC slurry. In this paper, the mechanism of ultrasonic pretreatment to promote flocculation and filtration of slurry was studied. The hydrophobic variation of the slurry surface was measured by contact angle and XPS. The flocculation properties of slurry were characterized using zeta potential and FBRM. The effects of filter cake porosity and ultrasonic pretreatment on slurry filtration resistance were calculated by L-F NMR and Darcy's theory. The results showed that the ultrasonic pretreatment promoted the flocculation and filtration performance of LRC slurry, increased the filtration rate, and decreased the cake moisture content. Meanwhile, the contact angle of LRC increased significantly from 50.1° to 67.8° after ultrasonic pretreatment, and the surface tension of the filtrate decreased from 69.5 to 53.31 mN/m. Ultrasonic pretreatment reduced the absolute value of the zeta potential of coal slurry from 24.8 to 21.0 mV, and the average chord length of flocs increased from 5-10 µm to 25-30 µm, thus weakening the electrostatic repulsion between coals to promote floc formation. In addition, the pore tests and filtration theory calculations showed that the ultrasonic pretreatment significantly improved the permeability of the filter cake to water and reduced the resistance to slurry during filtration. In particular, the mesopore porosity increased by 9.18%, and the permeability increased by 2.937 × 108 m2. Therefore, this contributed to the reduction of slurry filtration resistance. This research provides an efficient method for promoting the efficient filtration of slurry.

HIF1A-AS2 Promotes the Proliferation and Metastasis of Gastric Cancer Cells Through miR-429/PD-L1 Axis.

BACKGROUND: Gastric cancer (GC) is a common leading cause of cancer-related mortality of all malignancies. LncRNA hypoxia-inducible factor-1 alpha antisense RNA-2 (HIF1A-AS2) has been identified to involve in the development of GC. Therefore, we further explored the detailed molecular mechanism of HIF1A-AS2 in GC progression. METHODS: The expression of HIF1A-AS2, microRNA-429 (miR-429), and programmed cell death ligand 1 (PD-L1) was measured using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell proliferation, migration, and invasion abilities were detected by Cell Counting Kit-8 (CCK-8) or transwell assay. The interaction between miR-429 and HIF1A-AS2 or PD-L1 was confirmed by luciferase reporter assay. Murine xenograft model was established to investigate the role of HIF1A-AS2 in vivo. RESULTS: HIF1A-AS2 was elevated in GC tissues and cell lines. Functional experiments showed that HIF1A-AS2 knockdown inhibited GC cell proliferation, migration, and invasion in vitro, as well as hindered tumor growth in vivo. Moreover, HIF1A-AS2 directly bound to miR-429 based on bioinformatics prediction and luciferase assay, and inhibition of miR-429 abolished the effects of HIF1A-AS2 knockdown on GC cells. Furthermore, miR-429 directly targeted PD-L1, and overexpression of miR-429 suppressed GC tumorigenesis via PD-L1. Besides that, PD-L1 also performed an oncogenic role in GC cell proliferation and metastasis. Additionally, HIF1A-AS2 could indirectly regulate PD-L1 expression via sponging miR-429. CONCLUSION: HIF1A-AS2 is a dependable predictor of malignancy and prognosis in GC and functions as an oncogene to promote GC cell proliferation and metastasis by regulating miR-429/PD-L1 axis, indicating a new insight into the search for novel biomarkers and therapeutic strategies.

A Robust Thermal Infrared Vehicle and Pedestrian Detection Method in Complex Scenes.

In complex scenes, it is a huge challenge to accurately detect motion-blurred, tiny, and dense objects in the thermal infrared images. To solve this problem, robust thermal infrared vehicle and pedestrian detection method is proposed in this paper. An important weight parameter ß is first proposed to reconstruct the loss function of the feature selective anchor-free (FSAF) module in its online feature selection process, and the FSAF module is optimized to enhance the detection performance of motion-blurred objects. The proposal of parameter ß provides an effective solution to the challenge of motion-blurred object detection. Then, the optimized anchor-free branches of the FSAF module are plugged into the YOLOv3 single-shot detector and work jointly with the anchor-based branches of the YOLOv3 detector in both training and inference, which efficiently improves the detection precision of the detector for tiny and dense objects. Experimental results show that the method proposed is superior to other typical thermal infrared vehicle and pedestrian detection algorithms due to 72.2% mean average precision (mAP).

Detailed studies on the anticancer action of rosmarinic acid in human Hep-G2 liver carcinoma cells: evaluating its effects on cellular apoptosis, caspase activation and suppression of cell migration and invasion.

PURPOSE: Oral cancer is one among the devastating types of malignancies and imposes tremendous disease burden on humans. This study was undertaken to investigate the anticancer properties of a plant-derived flavanone, Blumeatin, against human oral cancer cells. Additionally, this study also attempted to unreveal the molecular mechanisms responsible for the anticancer properties of this molecule. METHODS: MTT assay was used for the assessment of cell viability. Transwell and wound healing assays were used for the determination of cell invasion and migration, respectively. Comet assay was used for the determination of cell viability. Transmission electron microscopy (TEM) analysis was done to assess the induction of autophagy. The protein expression was determined by western blot analysis. RESULTS: Blumeatin inhibited the growth of SCC-4 oral cancer cells with minimal cytotoxic effects against the normal hTRET-OME cells. The flow cytometric analysis showed that Blumeatin triggers DNA damage in the SCC-4 cells. Blumeatin also activated autophagy in SCC-4 cells which was accompanied with upregulation of LC3B and Beclin 1. This molecule also increased ROS and decreased the MMP levels in human SCC-4 cells. The effects of Blumeatin were also examined on the migration and invasion of the SCC-4 cells and it was revealed that the molecule suppresses both migration and invasion of the SCC-4 oral cancer cells. CONCLUSION: This study indicates that Blumeatin exhibits potent anticancer effects and points towards its use in the development of a new systemic therapy for oral cancer.

Thrombopoietin is associated with a prognosis of gastric adenocarcinoma.

OBJECTIVE Thrombopoietin (THPO) is well-known as a megakaryocyte growth and development factor (MGDF) involved in megakaryocyte proliferation and maturation. To explore the biological effects of THPO in gastric adenocarcinoma, we conducted this study. Methods: By accessing the TCGA database, the expression level of THPO was determined in tumor tissues. The association between THPO expression and clinical features, or prognostic significance was described by Cox regression analysis and Kaplan-Meier. The SiRNA method was used to decline the THPO expression; then cell viability, invasion, and migration were detected to verify the effects of the knockdown of THPO. qPCR and western blotting were implemented to examine the expression level of THPO. Results: The expression of THPO was increased in tumor tissue and cells, its high-regulation was associated with a poor prognosis in patients with gastric adenocarcinoma. Cell viability, invasion, and migration were suppressed in AGS with the down-regulation of THPO. Furthermore, on the basis of si-THPO transfection, E-cadherin was promoted while N-cadherin and Vimentin were attenuated. CONCLUSION Our results revealed that THPO may be a potent marker of gastric adenocarcinoma, providing a novel potential screening method for gastric adenocarcinoma.

Effect of the selection pressure of vaccine antibodies on evolution of H9N2 avian influenza virus in chickens.

H9N2 avian influenza virus has spread worldwide, and vaccination with an inactivated virus is currently the major prevention method in China. To further understand the effect of the selection pressure from antibodies on the evolution of H9N2 avian influenza virus, F/98 (A/Chicken/Shanghai/F/98), which is the vaccine representative of H9N2 avian influenza virus in East China, was used for serial passaging for 20 generations in chickens with and without vaccination. After plaque purification from trachea and lung tissues, 390 quasispecies were obtained. The second-generation quasispecies under the selection pressure of vaccine antibodies had undergone 100% antigen variation, while after passaging to the fifth generation, only 30-40% of the quasispecies displayed antigen variation when there was no selection pressure of vaccine antibodies, implying that the selection pressure of vaccine antibodies promotes the antigen variation of F/98. We found for the first time that there were three mutation hotspots in the HA genes of the quasispecies under the selection pressure of vaccine antibodies, which were K131R, A168T, and N201D. Moreover, under the selection pressure of vaccine antibodies, 10 amino acids (67-76) of the NA protein of all quasispecies were deleted, and PB2 of the quasispecies had undergone a high-frequency R355K mutation. However, without selection pressure of vaccine antibodies, NP had undergone two high-frequency mutations, namely, V186I and L466I, and a high-frequency mutation of L77I appeared in the NS gene. This result shows that the vaccine antibody selection pressure could control and regulate gene variation of the F/98 virus. Compared to that of the parental virus F/98, the EID50 of the twentieth passaged virus under the selection pressure of vaccine antibodies did not change, while the EID50 of the twentieth passaged virus without selection pressure of vaccine antibodies was significantly enhanced by 794 times. Furthermore, the twentieth passaged virus with selection pressure from vaccine antibodies lost its lethal ability in embryonated chicken eggs, whereas the EID50 of the twentieth passaged virus without selection pressure of vaccine antibodies increased to 6.3 times that of the F/98 strain. All the above results show that the selection pressure of vaccine antibodies promotes the antigen variation of H9N2 avian influenza virus and plays a role in regulating and controlling gene mutation of H9N2 avian influenza virus.

MiR-616 plays oncogenic role in hepatocellular carcinoma progression through suppressing PTEN expression and activating PI3K/AKT pathway.

Aims: Given their regulatory roles in gene expression, microRNAs play an important role in tumorigenesis. The current study aimed to explore the function and the related mechanisms of miR-616 in hepatocellular carcinoma (HCC).Methods: The expression of miR-616 was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Chi-square test was applied to estimate the association of miR-616 with clinical characteristics of HCC patients. Cell transfection was performed by Lipofectamine® 2000. MTT assay was used to detect cell proliferation, whereas cell motility was estimated using Transwell assay. The protein expression was detected using western blot.Results: MiR-616 was significantly up-regulated in HCC tissues and cells (p < .05 for all). Moreover, its elevated expression was positively correlated with lymph node metastasis (p = .008) and TNM stage (p = .012). Knockdown of miR-616 resulted in decreased cell proliferation, migration and invasion. Moreover, the inhibition of miR-616 significantly suppressed PI3K/AKT pathway. The bioinformatics analysis and luciferase reporter assay suggested that PTEN was a targeted gene of miR-616. PTEN had the capacity to reverse the oncogenic function of miR-616 in HCC.Conclusion: MiR-616 activates PI3K/AKT pathway through suppressing PTEN expression, thus promoting the progression of HCC.

The impact of APC polymorphisms on the transition from polyps to colorectal cancer (CRC).

OBJECTIVE: The purpose of this study was to investigate the function of APC polymorphisms (D1822V and E1317Q) on the transition from polyps to colorectal cancer (CRC). METHODS: 259 patients with polyps were included in the study. APC polymorphisms were genotyped via polymerase chain reaction (PCR) and subsequent sequencing. χ2 test was performed to analyze the relationship of APC polymorphisms or CRC occurrence with clinical features. COX regression was used to find out risk factors for CRC. Hazard ratio (HR) and 95% confidence interval (CI) represented the risk of CRC. RESULTS: Clinical information on sex, regular physical activity, smoking history, alcohol use and polyps types was recorded. Neither D1822V nor E1317Q polymorphism was associated with these factors. In following analysis, we found significant difference in the frequency of males between CRC and non-CRC patients (87.4% vs. 58.7%, P < 0.001). Distinct difference in the distribution of D1822V polymorphism was also observed between CRC and non-CRC patients (P = 0.001). In COX analysis, sex was identified as a risk factor for transition from polyps to CRC (HR = 2.442, 95%CI = 1.281-4.654). D1822V polymorphism tended to inhibit the transition process (HR = 0.286, 95%CI = 0.170-0.480). However, E1317Q seemed to have no significant effect on this process (HR = 1.042, 95%CI = 0.676-1.606). CONCLUSION: In a word, APC D1822V polymorphism has strong effect on the transition from polyps to CRC.

Thrombopoietin is associated with a prognosis of gastric adenocarcinoma

SUMMARY OBJECTIVE Thrombopoietin (THPO) is well-known as a megakaryocyte growth and development factor (MGDF) involved in megakaryocyte proliferation and maturation. To explore the biological effects of THPO in gastric adenocarcinoma, we conducted this study. Methods: By accessing the TCGA database, the expression level of THPO was determined in tumor tissues. The association between THPO expression and clinical features, or prognostic significance was described by Cox regression analysis and Kaplan-Meier. The SiRNA method was used to decline the THPO expression; then cell viability, invasion, and migration were detected to verify the effects of the knockdown of THPO. qPCR and western blotting were implemented to examine the expression level of THPO. Results: The expression of THPO was increased in tumor tissue and cells, its high-regulation was associated with a poor prognosis in patients with gastric adenocarcinoma. Cell viability, invasion, and migration were suppressed in AGS with the down-regulation of THPO. Furthermore, on the basis of si-THPO transfection, E-cadherin was promoted while N-cadherin and Vimentin were attenuated. CONCLUSION Our results revealed that THPO may be a potent marker of gastric adenocarcinoma, providing a novel potential screening method for gastric adenocarcinoma.

RESUMO OBJETIVO Trombopoetina (THPO) é um conhecido fator de desenvolvimento e crescimento megacariócito (MGDF) envolvido na proliferação e maturação de megacariócitos. Realizamos este estudo para explorar os efeitos biológicos do THPO no adenocarcinoma gástrico. Metodologia: O nível de expressão do THPO em tecidos tumorais foi determinado acessando a banco de dados TCGA. A associação entre a expressão de THPO e características clínicas ou relevância no prognóstico foi descrita através da análise de Kaplan-Meier e regressão de Cox. O método SiRNA foi utilizado para reduzir a expressão da THPO e, em seguida, a viabilidade, invasão, e migração celular foram detectadas para verificar os efeitos da redução do THPO. qPCR e western blotting foram utilizados para examinar o nível de expressão do THPO. Resultados: A expressão do THPO estava aumentada em tecido e células tumorais, esse aumento estava associado com um prognóstico negativo para pacientes com adenocarcinoma gástrico. A invasão e migração celular foram suprimidos em AGS com a redução do THPO. Além disso, com base na transfecção de si-THPO, a E-caderina foi promovida, enquanto a N-caderina e Vimentina foram atenuadas. Conclusão nossos resultados demonstram que o thpo pode ser um potente marcador de adenocarcinoma gástrico, com potencial para ser um novo tipo de triagem para adenocarcinoma gástrico.

Correlation Between MTHFR Polymorphisms and Hepatocellular Carcinoma: A Meta-analysis.

The correlation between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and hepatocellular carcinoma (HCC) remains controversial. Therefore, we performed this study to better assess the relationship between MTHFR polymorphisms and the likelihood of HCC. A systematic research of PubMed, Medline, and Embase was performed to retrieve relevant articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. A total of 15 studies with 8,378 participants were analyzed. In overall analyses, a significant association with the likelihood of HCC was detected for the rs1801131 polymorphism with fixed-effect models in recessive comparison (P = 0.002, OR = 0.62, 95% CI 0.43-0.82). However, no positive results were detected for the rs1801133 polymorphism in any comparison. Further subgroup analyses revealed that the rs1801131 polymorphism was significantly associated with the likelihood of HCC in Asians with both FEMs (recessive model: P < 0.0001, OR = 0.42, 95% CI 0.29-0.62; allele model: P = 0.004, OR =1.20, 95% CI 1.06-1.35) and random-effect models (recessive model: P = 0.002, OR = 0.47, 95% CI 0.29-0.75). Nevertheless, we failed to detect any significant correlation between the rs1801133 polymorphism and HCC. In conclusion, our findings indicated that the rs1801131 polymorphism may serve as a genetic biomarker of HCC in Asians.

Relationship between the expressions of PD-L1 and tumour-associated fibroblasts in gastric cancer.

Previous studies have focused on the changes of tumour cells in immune escape, and less is known about the effect of tumour microenvironment (TME) on immune escape. Tumour-associated fibroblasts (TAF) is an important part of the TME and has special physiological and biochemical characteristics, but the specific mechanism has not been clarified. In order to investigate the effect of TAF on the expression of PD-L1 in gastric cancer cells, gastric cancer cell lines MNK45, SGC7901 were non-contact co-culturing with TAF 1, 3 and 7 d via transwell. PD-L1 mRNA and protein expression were detected using qRT-PCR and FCM. Then, 95 cases of gastric cancer tissues were selected and evaluated PD-L1 and TAF expressions by immunohistochemical examination. The results showed that the mRNA and protein expression of PD-L1 in the experiment group were significantly higher than that in the control group. PD-L1 expression was associated with massive lymphocyte infiltration, diffuse/mixed histology and intratumoral TAFs in gastric cancers. In conclusion, TAFs promoted the growth in gastric cancer cell lines by increased the PD-L1 expression.

Correlation between Methylenetetrahydrofolate Reductase Polymorphisms and Hepatocellular Carcinoma: A Meta-Analysis.

BACKGROUND: The correlation between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and hepatocellular carcinoma (HCC) remains controversial. OBJECTIVES: We performed this study to better assess the relationship between MTHFR gene polymorphisms and the likelihood of HCC. METHODS: A systematic research of PubMed, Medline, and Embase was performed to retrieve relevant articles. ORs and 95% CIs were calculated. RESULTS: A total of 15 studies with 8,378 participants were analyzed. In overall analyses, a significant association with the likelihood of HCC was detected for the rs1801131 polymorphism with fixed-effect models (FEMs) in recessive comparison (p = 0.002, OR 0.62, 95% CI 0.43-0.82). However, no positive results were detected for the rs1801133 polymorphism in any comparison. Further subgroup analyses revealed that the rs1801131 polymorphism was significantly associated with the likelihood of HCC in Asians with both FEMs (recessive model: p < 0.0001, OR 0.42, 95% CI 0.29-0.62; allele model: p = 0.004, OR 1.20, 95% CI 1.06-1.35) and random-effect models (recessive model: p = 0.002, OR 0.47, 95% CI 0.29-0.75). Nevertheless, we failed to detect any significant correlation between the rs1801133 polymorphism and HCC. CONCLUSIONS: Our findings indicated that the rs1801131 polymorphism may serve as a genetic biomarker of HCC in Asians.

Androgen attenuates antitumor effects of gastric cancer cells by bone marrow mesenchymal stem cells via restricting the JNK signaling activation.

BACKGROUND: Researches on bone marrow mesenchymal stem cells (BMMSCs) have generated controversial results in tumor research. In the present study, we aimed to explore the functions of BMMSCs on gastric cancer and the possible mechanism in a mimicking microenvironment of the stomach. METHODS: Transwell co-cultured system was used to co-culture BMMSCs and gastric cancer SGC-7901 cells. In some experiments, androgen and its antagonist were added into the cells as required. Cell viability, cell apoptosis, mRNA and protein expressions of apoptosis- and JNK signaling- associated genes were respectively determined by performing cell counting kit-8, flow cytometry, quantitative real-time PCR and western blot. RESULTS: Androgen contributed to the growth of BMMSCs and SGC-7901 cells. In co-cultured system, BMMSCs not only suppressed SGC-7901 cell viability, induced cell apoptosis and promoted tumor necrosis factor (TNF)-α release, but also regulated the level of Bax/Bcl-2 and elevated the expressions of phosphorylation (p)-JNK and p53. After adding androgens, the anti-tumor effects of BMMSCs were weakened. Meanwhile, the antagonists of androgens could partially recover BMMSCs in vitro inhibitory effects on gastric cancer cells by activation of JNK signaling. CONCLUSIONS: This study demonstrated the important roles of BMMSCs on the growth and apoptosis of gastric cancer cells in vitro. Additionally, in the mimicking microenvironment of the stomach, androgen weakened the antitumor effects of BMMSCs by limiting JNK signaling activation, suggesting that androgen antagonist may be a promising adjuvant drug to BMMSCs in gastric cancer therapy.

MicroRNA-539 inhibits the progression of Wilms' Tumor through downregulation of JAG1 and Notch1/3.

BACKGROUND: Previous studies demonstrated that miR-539 play an important role in the carcinogenesis of some cancers. The aim of the present study was to determine the role of miR-539 in the pathogenesis of Wilms' Tumor (WT). METHODS: The expression level of miR-539 was measured by qRT-PCR in 42 WT tissues and SK-NEP-1 cell line. Protein expression of genes (E-cadherin, N-cadherin, Vimentin, Notch 1, Notch 3 and JAG1) was assessed by Western blot. The function of miR-539 was investigated in SK-NEP-1 cells by MTT and Transwell assays. The relationship between miR-539 and JAG1 was verified by a dual luciferase assay in SK-NEP-1 cells. RESULTS: The expression level of miR-539 was significantly decreased in WT tissues. Downregulation of miR-539 was closely related to NWTS-5 stage, lymph node metastasis and histological type of WT patients. Furthermore, low miR-539 expression was associated with a shorter overall survival rate in WT patients. In vitro, overexpression of miR-539 suppressed proliferation, migration and invasion of SK-NEP-1 cells. In addition, JAG1 was a direct target of miR-539. MiR-539 inhibited the development of WT by inhibiting JAG1-Notch1/3 expressing and blocking EMT. CONCLUSION: MiR-539 inhibited the progression of WT through downregulation of JAG1 and Notch1/3.

Effect of annexin II-mediated conversion of plasmin from plasminogen on airborne transmission of H9N2 avian influenza virus.

Airborne transmission plays an important role in dissemination of H9N2 subtype avian influenza virus. Annexin II (A2)-mediated activation of plasminogen (PLG) promotes cleavage of the influenza virus HA protein and viral replication, resulting in enhanced pathogenesis. In this study, airborne transmission competent and defective strains of H9N2 influenza virus, SH7 and SH14, respectively, were used to investigate the effect of A2 on airborne spread. The results showed that A2 protein was increased in SH7 virions compared with SH14 particles, the binding ability of the SH7-infected MDCK cells to PLG was significantly higher than the SH14-infected cells, and influence efficiency of the PLG on replicated ability of SH7 virus was significantly stronger than that of SH14 virus, who spread without airborne route, indicating that the annexin 2 (A2) can bind PLG and contributes to SH7 with high replication ability. Furthermore, the copies of SH7 in the airborne infected chickens under inhibited by 6-AHA were significantly decreased, suggesting that the release of H9N2 avian influenza virus were reduced by inhibiting the conversion of PLG to PL, ultimately resulting in reduced airborne transmission of H9N2 avian influenza virus. In summary, A2-mediated conversion of PLG to PL plays a role in the airborne transmission capacity of H9N2 avian influenza viruses, and this interaction may represent potential targets for prevention and treatment of influenza virus infection.