Reproductive traits associated with invasiveness in Conyza sumatrensis

Conyza sumatrensis （Retz.） E. Walker, a member of Asteraceae, is a highly invasive species. However, its reproduction biology remains poorly known. To understand the role of reproductive traits in successful invasion of the species, we studied several traits of its reproductive system： the miniature capitulum and gynomonoecious sexual system, the biology and phenology of capitula and florets, pollen/ovule ratio, the mating system （selfcompatibility）, flower visitors, physical traits and dispersal potential of achenes, germination potential of achenes from manually pollinated capitula, and the association of these traits with invasiveness. Our study showed that the reproductive traits of autonomous seed production, versatile mating system of self- and cross-pollination, and generalized pollination system might contribute to the species＇ successful invasive capability. The invasiveness was further enhanced by the high and rapid production of achenes, as well as the high percentage, rapid germination rate and high dispersal capability of achenes. It was concluded that in annual or winter-annual weeds, autonomous seed production contributed significantly to the invasiveness of the species.

Association of Expression of Leucine-rich Repeats and Immunoglobulin-like Domains 2 Gene with Invasiveness of Pituitary Adenoma

The Leucine-rich repeats and immunoglobulin-like domains-2（LRIG2） gene expression in pituitary adenoma and its correlation with tumor invasiveness were studied.The expression of LRIG2 mRNA and protein in human pituitary adenoma obtained surgically was detected by RT-PCR（39 cases） and immunohistochemical staining（30 cases）.It was found that LRIG2 was mostly localized at the nucleus of the pituitary adenoma cells.Its expression was significantly higher in the invasive cases than in the non-invasive cases.LRIG2 protein was positive in 14 cases out of 21 cases of invasive adenoma,but only 2 cases were positive in 9 cases of non-invasive adenoma.The positive expression rate of LRIG2 mRNA was 91.3% in invasive cases（total 23 cases） and 62.5% in non-invasive cases（total 16 cases）,respectively.LRIG2 gene is overexpressed in invasive pituitary adenoma.It may play an important role in pituitary adenoma invasiveness and further studies are necessary to elucidate the mechanism under this phenomenon.

UROKINASE-TYPE PLASMINOGEN ACTIVATOR,ITS RECEPTOR AND INHIBITOR EXPRESSION IN HEPATOCELLULAR CARCINOMA RELATION TO CANCER INVASIVENESS AND PROGNOSIS

Objective: To study the relevance of uPA, uPAR and PAI 1 to hepatocellular carcinoma (HCC) Methods: The expression at protein level of uPA, uPAR and PAI 1 was determined in 48 cases of HCC and 12 cases of benign tumors of liver (as control) by immunohistochemistry Results: When compared to cancer adjacent liver tissue and the control, positive rate of immune staining for uPA, uPAR and PAI 1 on cell membrane were significantly higher in HCC cells ( P <0 05) Positive staining of uPA and uPAR was seen in 16 of 22 and 19 of 22 cases of HCC with invasion, respectively ( P <0 01 and P <0 001) In 8 of 8 cases with cancer embolus, and in 6 of 6 cases with lymph node metastasis was the expression of positive uPAR Compared with 2 of 17 cases without recurrence, uPAR was positive in 15 of 17 recurrent cases ( P <0 01) In 36 cases who survived, 17 was positive uPAR and 15 positive PAI 1, while in 12 cases who died 2 years after surgery, 12 were positive for uPAR and 9 positive PAI 1, respectively ( P <0 01 and P <0 05) In 15 positive cases for all three parameters, 11 had cancer invasion and 7 died within 2 years, while in negative cases, 2 had invasion and none died within 2 years ( P <0 05) Conclusion: Expression of uPA, uPAR and PAI 1 is increased in HCC, uPA and uPAR may contribute significantly to HCC invasion and metastasis uPAR and PAI 1 are associated with poor prognosis of HCC

The Expression of Integrinβ1 and FAK in Pituitary Adenomas and Their Correlation with Invasiveness

The expression and possible role of integrin-focal adhesion kinase signal pathway in invasive pituitary adenomas were explored. Forty-nine human pituitary adenomas were detected for the expression of integrinβ1 （INTβ1） and focal adhesion kinase （FAK） by immunohistochemistry, and their correlation with the invasiveness of pituitary adenomas as well as between themselves was ana- lyzed. The results showed that INTβ1 was expressed in 46 cases （93.9%） and FAK in 36 cases （73.5%）, respectively, and their expression levels were highly correlated with tumor invasiveness, but not with the tumor types. It was suggested that the integrin-focal adhesion kinase signal pathway plays a role in the invasiveness of pituitary adenomas.

Effect of ERBB2 expression on invasiveness of glioma TJ905 cells

Objective:To investigate the influence and possible mechanism of ERBB2 expression on the invasiveness of glioma cells.Methods:Glioma TJ905 cells were separated and cultured.ERBB2shRNA and overexpressing vectors were constructed,which were then transfected.The ERBB2expression was up-regulated or down-regulated.Changes of invasiveness of TJ905 cells were detected by Transwell assay,and the expressions of matrix metalloprotease(MMP)-2 and MMP-9were measured by Western bolt.Results:ERBB2 shRNA transfection vector could effectively inhibit expression of ERBB2:while ERBB2 overexpressing vector transfection could significantly improve the expression of ERBB2 in TJ905 cells.Transwell assay showed that when ERBB2expression was down-regulated,the invasiveness of TJ905 cells was notably decreased;when ERBB2 expression was up-regulated,the invasiveness of TJ905 cells was markedly increased.Meanwhile.Western blot indicated that down-regulating ERBB2 inhibited the expression of MMP-2 and MMP-9,while up-regulating ERBB2 enhanced their expressions.Conclusions:ERBB2 expression is closely related in the invasiveness of glioma TJ905 cells.

Assessment for the minimal invasiveness of laparoscopic liver resection by interleukin-6 and thrombospondin-1

BACKGROUND Laparoscopic surgery has been introduced as a minimally invasive technique for the treatment of various field.However,there are few reports that have scientifically investigated the minimally invasive nature of laparoscopic liver resection(LLR).AIM To investigate whether LLR is scientifically less invasive than open liver resection.METHODS During December 2011 to April 2015,blood samples were obtained from 30 patients who treated with laparoscopic(n=10,33%)or open(n=20,67%)partial liver resection for liver tumor.The levels of serum interleukin-6(IL-6)and plasma thrombospondin-1(TSP-1)were measured using ELISA kit at four time points including preoperative,immediate after operation,postoperative day 1(POD1)and POD3.Then,we investigated the impact of the operative approaches during partial hepatectomy on the clinical time course including IL-6 and TSP-1.RESULTS Serum level of IL-6 on POD1 in laparoscopic hepatectomy was significantly lower than those in open hepatectomy(8.7 vs 30.3 pg/mL,respectively)(P=0.003).Plasma level of TSP-1 on POD3 in laparoscopic hepatectomy was significantly higher than those in open hepatectomy(1704.0 vs 548.3 ng/mL,respectively)(P=0.009),and have already recovered to preoperative level in laparoscopic approach.In patients with higher IL-6 Levels on POD1,plasma level of TSP-1 on POD3 was significantly lower than those in patients with lower IL-6 Levels on POD1.Multivariate analysis showed that open approach was the only independent factor related to higher level of IL-6 on POD1[odds ratio(OR),7.48;95%confidence interval(CI):1.28-63.3;P=0.02].Furthermore,the higher level of serum IL-6 on POD1 was significantly associated with lower level of plasm TSP-1 on POD3(OR,5.32;95%CI:1.08-32.2;P=0.04)in multivariate analysis.CONCLUSION In partial hepatectomy,laparoscopic approach might be minimally invasive surgery with less IL-6 production compared to open approach.

IN VIVO COMPARATIVE OBSERVATION ON THE INVASIVENESS OF VARIOUS ORGANS BY DIFFERENT LEUKEMIA CELLS

Using patho-morphological method and transplantation bio-assay, the in vivo invasiveness of leukemia cells is three transplantable mouse T cell leukemia models was comparatively studied. The results showed that the invasion to the liver was consistent, but that to other organs was obviously different. L615 and L7212 leukemia cells preferred to the bone marrow and spleen than to the peritoneum while L7811 leukemia cells were just the opposite. Transplantation bio-assay demonstrated that leukemia cells were present in the bone marrow of L615 mice as early as 6 hours after leukemic cell inoculation, but no leukemia cells was detected in bone marrow of L7811 mice 2 days after inoculation. In the terminal phase, L615 mice bone marrow became filled with leukemia cells, but L7811 mice bone marrow contained only a few leukemia cells. The difference of invasiveness of leukemia cells among organs is probably related to "homing" receptor. The same type of leukemia cells may possess multiple "homing" receptor.

Vibramycin inhibits the expression of MMP-2 and the invasiveness of PC-3 cells in vitro

Objective To study the inhibition of vibramycin on the expression of matrix metalloproteinase-2 (MMP-2) and the invasiveness of androgen-independent prostatic carcinoma cell line PC - 3 in vitro. Methods Immunohistochemistry stain and transwell chamber were used to investigate the expression of MMP-2 in different concentration of vibramycin treated PC-3 cells and the invasive ability of different concentration of vibramycin treated PC-3 cell. Results The positive rate of MMP-2 inJune 2003 Vol12 No2 PC-3 cells was decreased at a concentration of 5 mg/L of vibramycin and decreased dramatically at the concentration of 10 mg/L. The cells moved throuth the membrane was(82. 0 ± 4.6)/field in the control group, while decreased to(26.1 ±3.6),(7.2 ±2.2) and(3.3± 0.7)/field in 5,10 and 20 mg/L vibramycin treated PC-3 cell respectively. Conclusion Vibramycin can inhibit the invasiveness and metastatasis of PC-3 cells, the mechanism of which is related to the inhibition of MMP-2 in PC-3 cell.10refs.

Lower serum folate is associated with development and invasiveness of gastric cancer

AIM: To evaluate the associations of serum folate levelwith development, invasiveness and patient survival of gastric cancer. METHODS: In this nested case-control study, patients with newly diagnosed gastric cancer undergoing gastrectomy were enrolled, and patients receiving chemotherapy prior to surgery, with other concurrent malignancy, or of the aboriginal and alien populations were excluded. In total, 155 gastric cancer patients and 149 healthy controls were enrolled for determination of serum folate levels and their correlation with gastric cancer. Using the median value of serum folate computed among the overall population as the cutoff value, the associations between serum folate and gastric cancer in all cases and different age and gender subgroups were analyzed by multivariate logistic regression analysis. In the patient cohort of gastric cancer, receiver-operating characteristic analyses were performed to calculate the best cutoff values of serum folate, and the associations between serum folate levels and clinicopathological features were further analyzed by multivariate regression analysis. Survival analyses were conducted using the Cox proportional hazards model.RESULTS: The mean serum folate level was significantly lower in gastric cancer patients than that in controls(3.71 ± 0.30 ng/mL vs 8.00 ± 0.54 ng/mL, P < 0.01), and folate levels were consistently lower in gastric cancer patients regardless of age and gender(all P < 0.01). Using the median serum folate value as the cutoff value, low serum folate was significantly associated with gastric cancer risk in the whole population(OR = 19.77, 95%CI: 10.54-37.06, P < 0.001) and all strata(age < 60 years OR = 17.39, 95%CI: 7.28-41.54, age ≥ 60 years(OR = 21.67, 95%CI: 8.27-56.80), males(OR = 17.95, 95%CI: 7.93-40.62), and females(OR = 20.95, 95%CI: 7.66-57.31); all P < 0.001. In the patient cohort of gastric cancer, the respective cutoff values showed that low serum folate levels were significantly associated with serosal invasion(OR = 2.54, 95%CI: 1.23-5.23), lymphatic invasion(OR = 2.23, 95%CI: 1.17-4.26), and liver metastasis(OR =6.67, 95%CI: 1.28-34.91) of gastric cancer(all P < 0.05). Serum folate level below 1.90 ng/mL was associated with poor patient survival(HR = 1.84, 95%CI: 1.04-3.27, P < 0.05) in univariate analysis.CONCLUSION: Lower serum folate levels were significantly associated with gastric cancer development and invasive phenotypes. The role of folate depletion in gastric cancer invasion warrants further study.

Silencing MTA1 by RNAi Reverses Adhesion, Migration and Invasiveness of Cervical Cancer Cells (SiHa) via Altered Expression of p53, and E-cadherin/β-catenin Complex

It has been reported that metastasis-associated gene 1 （Mta1） is overexpressed in many malignant tumors with high metastatic potential. In addition, some studies indicated that MTA1 participated in invasion, metastasis, and survival of cancer cells by regulating cell migration, adhesion and proliferation. But the role of MTA1 is unclear in vitro in the development of cervical cancer cells. This study investigated whether and how MTA1 mediated cell proliferation, migration, invasion and adhesion in cervical cancer. MTA1 expression level was detected by Western blot in two cervical cancer cell lines of different invasion potentials. The effects of MTA1 expression on SiHa cell apoptosis, cycle, proliferation, migration, invasion and adhesion were tested by flow cytometry, MTT, wound-healing assay, Transwell assay and adhesion assay, respectively. The expression levels of p53, E-cadherin, and β-catenin activity were evaluated in untreated and treated cells. The results showed that MTA1 protein expression was significantly higher in SiHa than in HeLa, which was correlated well with the potential of migration and invasion in both cell lines. Furthermore, the cell invasion, migration and adhesion capabilities were decreased after inhibition of MTA1 expression mediated by Mta1-siRNA transfection in SiHa. However, no significant differences were found in cell apoptosis, cycle, and proliferation. In addition, E-cadherin and p53 protein levels were significantly up-regulated, while β-catenin was significantly down-regulated in SiHa transfected with the siRNA. These results demonstrated that MTA1 played an important role in the migration and invasion of cervical cancer cells. It was speculated that the decreased migration and invasion capability by inhibiting the MTA1 expression in the SiHa cell line may be mediated through the altered expression of p53, and E-cadherin/β-catenin complex. MTA1 could serve as a potential therapeutic target in cervical cancer.

Targeted Silencing of Heparanase Gene by Small Interfering RNA Inhibits Invasiveness and Metastasis of Osteosarcoma Cells

The effects of targeted silencing of heparanase gene by small interfering RNA（siRNA） on invasiveness and metastasis of osteosarcoma cells（MG63 cells） were investigated in the present study.Two complementary oligonucleotide strands were synthesized and inserted into pGenesil-1 vector based on the mRNA sequence of heparanase gene.The expression vector containing short hairpin RNA（pGenesil-shRNA） was constructed successfully.MG63 cells were randomly allocated into 3 groups：blank group,empty vector（pGenesil） transfected group and expression vector（pGenesil-shRNA） transfected group.Under the induction of Lipofectamine 2000,the recombinants were transfected into MG63 cells.Heparanase gene expression level was detected by RT-PCR and Western blotting.Cell prolifera-tion was measured by MTT assay.Cell invasiveness and metastasis were examined by cell adhesion and Transwell-ECM assays.HUVECs migration assay was applied for the detection of angiogenesis.As compared with negative controls,the mRNA and protein expression levels of heparanase were down-regulated by 76.1%（P0.01） and 75.3%（P0.01） respectively in the pGenesil-shRNA transfected group.Meanwhile,the proliferation,adhesiveness,invasiveness and angiogenesis properties of MG63 cells were all significantly inhibited.It was suggested that targeted silencing of heparanase gene by siRNA could dramatically inhibit the invasiveness and metastasis of osteosarcoma cells.

Methanol extract of Codium fragile inhibits tumor necrosis factor-ɑ-induced matrix metalloproteinase-9 and invasiveness of MDA-MB-231 cells by suppressing nuclear factor-κB activation

Objective:To evaluate whether the methanol extract of Codium fragile(MECF) regulates tumor necrosis factor-α(TNF-α)-induced invasion of human breast cancer MDA-MB-231 cells by suppressing matrix metalloproteinase-9(MMP-9).Methods:Reverse transcriptionpolymerase chain reaction(RT-PCR) and western blot analysis were performed to analyze the expression of MMP-9 and nuclear factor-κB(NF-κB) subunits,p65 and p50,and IκB in MDA-MB-231 cells.3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide(MTT) assay was used for cell viability.MMP-9 activity and invasion were measured by gelatin zymography and a matrigel invasion assay,respectively.NF- κB activity was measured by an electrophoretic mobility shift assay and luciferase activity.Results:MECF had no effects on cell viability up to a concentration of 100 μg/mL in human breast cancer MDA-MB-231 cells regardless of the presence of TNF-α.MDA-MB-231 cells that were stimulated with TNF-α showed a marked increase of invasion compared to the untreated control,whereas pretreatment with MECF downregulated the TNF-α-induced invasion of MDA-MB-231 cells.Additionally,zymography,western blot analysis,and reverse transcriptase-polymerase chain reaction(RT-PCR) confirmed that MECF decreased TNF-α-induced MMP-9 expression and activity which is a key regulator for cancer invasion.According to an electrophoretic morbidity shift assay,pretreatment with MECF in MDA-MB-231 cells significantly decreased the TNF-α-induced DNA-binding activity of nuclear factor- κB(NF- κB),which is an important transcription factor for regulating cancer invasion-related genes such as MMP-9.Furthermore,treatment with MECF sustained the expression of p65 and p50 in response to TNF-α in the cytosolic compartment.The luciferase assay demonstrated that MECF attenuated TNF-α-induced NF- κB luciferase activity.Conclusion:MECF exhibited its antiinvasive capability by downregulating TNF-α-induced MMP-9 expression,resulting from the suppression of NF- κB activity in the human breast cancer cell line MDA-MB-231.

Priming the seed:Helicobacter pylori alters epithelial cell invasiveness in early gastric carcinogenesis

Helicobacter pylori(H. pylori) infection is a wellestablished risk factor for the development of gastric cancer(GC), one of the most common and deadliest neoplasms worldwide. H. pylori infection induces chronic inflammation in the gastric mucosa that, in the absence of treatment, may progress through a series of steps to GC. GC is only one of several clinical outcomes associated with this bacterial infection, which may be at least partially attributed to the high genetic variability of H. pylori. The biological mechanisms underlying how and under what circumstances H. pylori alters normal physiological processes remain enigmatic. A key aspect of carcinogenesis is the acquisition of traits that equip preneoplastic cells with the ability to invade. Accumulating evidence implicates H. pylori in the manipulation of cellular and molecular programs that are crucial for conferring cells with invasive capabilities. We present here an overview of the main findings about the involvement of H. pylori in the acquisition of cell invasive behavior, specifically focusing on the epithelial-to-mesenchymal transition, changes in cell polarity, and deregulation of molecules that control extracellular matrix remodeling.

The Effect of RhoC siRNA on the Invasiveness and Proliferation of Human Cervical Cancer Cell Line SiHa Cells

This study investigated the effect of RhoC GTPase on the proliferation and metastasis of cervical cancer cells, SiHa cells, in vitro. RhoC siRNA was introduced into SiHa cells to silence the RhoC gene. The mRNA and protein expression of RhoC, before and after RhoC siRNA transfection, was examined by RT-PCR and Western blotting, respectively. The proliferation and apoptosis of SiHa cells were examined by MTT assay and flow cytometry （FACS）, respectively. Adhesive rate was evaluated by Matrigel adhesive assay, and the invasive capability and migration capability were assessed by transwell invasive assay and migration assay, respectively. The results showed that after the RhoC siRNA transfection, the mRNA and protein expression of RhoC was down-regulated in SiHa cells. The down-regulation of RhoC GTPase did not affect the cell proliferation and apoptosis （P〉0.05）, but it did suppress SiHa cells＇ adhesion to matrigel （P〈0.01）, the invasive capability （P〈0.01） and the migration capability （P〈0.01）. It was concluded that RhoC obviously promotes the adhesion, invasion and migration of SiHa cells in vitro, but not proliferation and apoptosis, suggesting that RhoC plays an important role in the progression in cervical cancer.

Chasing the queens of the alien predator of honeybees: A water drop in the invasiveness ocean

The Yellow-legged hornet, Vespa velutina , was accidentally introduced in France in 2004, and then spread rapidly through the French territory but also to adjacent European countries (Spain, Portugal, and Belgium). During summer and autumn, V. velutina workers hunt domestic honeybees, Apis mellifera, for feeding their larvae. The impact of this alien species is mainly economic, beekeepers experiencing heavy colony losses, but also ecological, V. velutina hunting other pollinators. In their year-round life cycle, nest initiation by single queen during spring is the critical stage. In invaded areas, spring queen trapping using food baits has been promoted by apicultural unions in order to limit V. velutina population expansion. The goals of this work were 1) to evaluate the yield of this method, 2) to identify appropriate sites for trapping, 3) to identify potential optimal climatic windows of capture, and 4) to quantify the impact on local entomofauna. Our results showed that water proximity enhances trapping but not beehives proximity, and that trapping is inefficient if average week temperatures are below 10°C. Although the trapping effect on biodiversity should be studied more carefully, spring queen trapping is highly questionable unless specific attractants could be proposed.

Germination Biology and Occurrence of Polyembryony in Two Forms of Cats Claw Creeper Vine, Dolichandra unguis-cati (Bignoniaceae): Implications for Its Invasiveness and Management

Cat’s claw creeper vine, Dolichandra unguis-cati (L.) Lohmann (syn. Macfadyena unguis-cati (L.) Gentry), is a major environmental weed in Australia. Two forms (“long” and “short” pod) of the weed occur in Australia. This investigation aimed to evaluate and compare germination behavior and occurrence of polyembryony (production of multiple seedlings from a single seed) in the two forms of the weed. Seeds were germinated in growth chambers set to 10/20&deg;C, 15/25&deg;C, 20/30&deg;C, 30/45&deg;C and 25&deg;C, representing ambient temperature conditions of the region. Germination and polyembryony were monitored over a period of 12 weeks. For all the treatments in this study, seeds from the short pod form exhibited significantly higher germination rates and higher occurrence of polyembryony than those from the long pod form. Seeds from the long pod form did not germinate at the lowest temperature of 10/20&deg;C;in contrast, those of the short pod form germinated under this condition, albeit at a lower rate. Results from this study could explain why the short pod form of D. unguis-cati is the more widely distributed form in Australia, while the long pod form is confined to a few localities. The results have implication in predicting future ranges of both forms of the invasive D. unguis-cati, as well as inform management decisions for control of the weed.

Hypoxia-induced enhancement of cell invasiveness in SMMC7721 hepatocellular carcinoma cells

Objective To explore the effects of hypoxia(1% O2)on the ability of cell invasiveness and expression of KAI1/CD82 in SMMC7721 hepatocellular carcinoma cells.Methods SMMC7721 hepatocellular carcinoma cells were cultured by hypoxia(1% O2)in vitro,and the ability of cell invasiveness was analyzed by cell invasion assay.Immunohistochemistry staining technique was used to evaluate the protein expression of KAI1/CD82.Results Cell invasion assay revealed that hypoxia enhanced the ability of invasiveness of hepatocellular carcinoma cells.In addition,KAI1/CD82 protein expression was positive in cultured SMMC7721 hepatocellular carcinoma cells,and it was located diffusedly in the cytoplasm and on the membrane.KAI1/CD82 protein expression was down-regulated when mediated by hypoxia;at the same time,it showed a time-effect relationship.Conclusion Hypoxia can enhance invasiveness of hepatocellular carcinoma cells.The down-regulation of KAI1/CD82 expression may play a certain role in those courses.

Global warming scenarios for the Eastern Adriatic Sea indicate a higher risk of invasiveness of non-native marine organisms relative to current climate conditions

Globally,marine bioinvasions threaten marine ecosystem structure and function,with the Mediterranean Sea being one of the most affected regions.Such invasions are expected to increase due to climate change.We conducted a risk screening of marine organisms(37 fishes,38 invertebrates,and 9 plants),both extant and‘horizon’(i.e.,not present in the area but likely to enter it).Based on expert knowledge for the Eastern Adriatic Sea coasts of Slovenia,Croatia,and Montenegro,screenings were conducted under both current and predicted climate conditions indicating with an increase in sea surface temperature and salinity of the Adriatic Sea together with changes in precipitation regime.Our aims were to:(1)identify non-native extant and horizon marine species that may pose threats to native biodiversity and(2)evaluate the risk of invasiveness of the selected species under current and predicted climate conditions.Of the 84 species screened,there was an increase in those ranked as‘high risk’from 33(39.3%)under current climate conditions and to 47(56.0%)under global warming scenarios.For those ranked as‘very high’risk,the increase was from 6(7.1%)to 21(25.0%).Amongst the screened species,the already established high-risk species Pacific oyster Magallana gigas and Atlantic blue crab Callinectes sapidus represent a threat to ecosystem services.Given the under-representation of marine species in the current European Union List,the species we have ranked as high to very high risk should be included.

Abnormal regulation of chemokine TECK and its receptor CCR9 in the endometriotic milieu is involved in pathogenesis of endometriosis by way of enhancing invasiveness of endometrial stromal cells

The chemokine thymus-expressed chemokine(TECK),which regulates T-cell development and tissue-specific homing,has been identified as a potential contributor to the pathogenesis and progression of endometriosis.Dioxin(2,3,7,8-tetrachlorodibenzo-p-dioxin,TCDD),an air pollutant,and estrogen also appear to be involved in endometriosis.Both endometrial stromal cells(ESCs)and the combination of 17b-estradiol and TCDD increase the secretion of TECK in the endometriosis-associated cells and promote the invasiveness of ESCs by increasing expression of matrix metalloproteinase(MMP)-2 and MMP-9.Anti-TECK neutralizing antibodies can effectively inhibit the invasiveness of ESCs and the expression of MMP-2 and MMP-9 in the cells.Interestingly,the expression of chemokine C receptor 9(CCR9)and its ligand TECK increases significantly in the endometriotic milieu of patients with endometriosis.Therefore,the over-expressed TECK interacts with CCR9 on the ESCs in the endometriotic milieu,which may contribute to the onset and progression of endometriosis.

Dexamethasone enhances invasiveness ofAspergillusfumigatus conidia and fibronectin expression in A549 cells

Background The efficacies of current treatments for invasive aspergillus （IA） are unsatisfactory and new therapeutic targets or regimens to treat IA are urgently needed. Previous studies have indicated that the ability of conidia to invade host cells is critical in IA development and fibronectin has a hand in the conidia adherence process. In the clinical setting, many patients who receive glucocorticoid for extended periods are susceptible to Aspergillus fumigatus （A. fumigatus） infection, for this reason we investigated the effect of glucocorticoid on conidia invasiveness by comparing the invasiveness of A. fumigatus conidia in the type II human alveolar cell line （A549） cultured with different concentrations of dexamethasone. We also explored the relationships between dexamethasone and fibronectin expression. Methods Following culture with anti-fibronectin antibodies and/or dexamethasone, type II human alveolar A549 cells were infected with conidia of A. fumigatus. After 4 hours, the extracellular free conidia were washed away and the remaining immobilized conidia were released using Triton-X 100 and quantified by counting the colony-forming units. The invasiveness of conidia was measured by calculating the invasion rate （%）. The transcription of the fibronectin gene in cells cultured with different concentrations of dexamethasone for 24 hours was tested by fluorogenic quantitative RT-PCR while the expression of fibronectinin cells cultured for 48 hours was tested by Western blotting and immunocytochemistry. Results A significant reduction in the invasiveness of conidia was seen in the cells cultured with anti-fibronectin antibody （（14.42±1.68）% vs. （19.17±2.53）%, P 〈0.05）, but no significant difference was observed in cells cultured with a combination of anti-fibronectin antibody and dexamethasone （6.37×10^-5 mol/L）. There was no correlation between the dexamethasone concentration and the invasiveness of conidia after dexamethasone pretreatment of cells for 4 hours. In contrast, after pretreated for 24 hours, the invasiveness of conidia in the presence of 6.37×10^-5 mol/L dexamethasone （（24.66±2.41）%） was higher than for the control （（19.17±2.53）%） and the 0.25×10^-5 mol/L group （（19.93±3.06）%）, and the invasiveness in the 1.27×10^-5 mol/L group （（22.47±2.46）%） was also higher than in the control, P 〈0.05. The relative transcripts of the fibronectin gene after exposure to 6.37× 10^-5 mol/L dexamethasone （9.19×10^-3±1.2×10^-3） was higher than for the control （4.61 ± 10^-3±1.54× 10^-3） and the 0.25× 10^-5 mol/L group （6.20× 10^-3±1.93× 10^-3）, and expression in the 1.27× 10^-5 mol/L group （7.94× 10^-3±2.24×10^3） was also higher than for the control, P 〈0.05. High concentrations of dexamethasone promoted fibronectin production after culture for 48 hours. Conclusions Dexamethasone can increase invasiveness of A. fumigatus conidia by promoting fibronectin expression. This may partially explain why patients who are given large doses of glucocorticoids for extended periods are more susceptible to A. fumigatus infection.