Induction of uPA gene expression by the blockage of E-cadherin via Src- and Shc-dependent Erk signaling

Loss of E-cadherin-mediated cell-cell adhesion and expression of proteolytic enzymes characterize the transition from benign lesions to invasive, metastatic tumor, a rate-limiting step in the progression from adenoma to carcinoma in vivo. A soluble E-cadherin fragment found recently in the serum and urine of cancer patients has been shown to disrupt cell-cell adhesion and to drive cell invasion in a dominant-interfering manner. Physical disruption of cell-cell adhesion can be mimicked by the function-blocking antibody Decma. We have shown previously in MCF7 and T47D cells that urokinase-type plasminogen activator (uPA) activity is up-regulated upon disruption of E-cadherin-dependent cell-cell adhesion. We explored the underlying molecular mechanisms and found that blockage of E-cadherin by Decma elicits a signaling pathway downstream of E-cadherin that leads to Src-dependent Shc and extracellular regulated kinase (Erk) activation and results in uPAgene activation. siRNA-mediated knockdown of endogenous Src-homology collagen protein (Shc) and subsequent expression of single Shc isoforms revealed that p46(Shc) and p52(Shc) but not p66(Shc) were able to mediate Erk activation. A parallel pathway involving PI3K contributed partially to Decma-induced Erk activation. This report describes that disruption of E-cadherin-dependent cell-cell adhesion induces intracellular signaling with the potential to enhance tumorigenesis and, thus, offers new insights into the pathophysiological mechanisms of tumor development.     

Natural compounds of Palestine flora. Comparison analysis by static headspace and steam distillation GC-MS of semivolatile secondary metabolites from leaves of cultivated Palestinian Majorana syriaca

BACKGROUND: A comparative analysis by using static headspace (HS) and steam distillation (SD) GC-MS of the volatile and the semi-volatile secondary metabolites from leaves of cultivated Majorana syriaca. METHODS: The essential oils endogenous to cultivated thyme were isolated and identified by HS-GC-MS technology and compared to those from SD-GC-MS. RESULTS: The HS-GC-MS results showed that the Palestinian cultivated thyme is rich in monoterpene hydrocarbons and phenolic monoterpenes such as alpha-phellandrene, alpha-pinene, beta-myrcene, m-cymene, p-cymene, gamma-terpinene, thymol and carvacrol. In all the samples gamma-terpinene, p-cymene, thymol and carvacrol were the most abundant compounds. CONCLUSIONS: HS and SD-GC-MS have proved that most of the cultivated thyme samples examined has thymol isomer as the major phenolic constituent.     

Synthesis and biological evaluation of benzoisothiazole derivatives possessing N,N-dimethylformimidamide group as 5-HT₆ receptor antagonists

A series of novel N,N-dimethyl-N'-(5-(Ar-sulfonamido) benzo[d]isothiazol-3-yl)formimidamides was designed and synthesized as 5-HT(6) ligands. Here N,N-dimethyl formimidamides was used as a replacement for an aminoethyl moiety. In vitro functional assays demonstrated compounds 9b and 9i significantly inhibited the 5-HT-induced Ca(2+) increases (9b; IC(50)=0.36 μM and 9i; IC(50)=0.44 μM), indicating that 9b and 9i were potent 5-HT(6) receptor antagonists. Compounds 9i also showed good selectivity on the 5-HT(6) over 5-HT(4) and 5-HT(7) receptors.     

Targeting N-acyl-homoserine-lactones to mitigate membrane biofouling based on quorum sensing using a biofouling reducer

Exploring novel biological anti-quorum sensing (QS) agents to control membrane biofouling is of great worth in order to allow sustainable performance of membrane bioreactors (MBRs) for wastewater treatment. In recent studies, QS inhibitors have provided evidence of alternative route to control membrane biofouling. This study investigated the role of Piper betle extract (PBE) as an anti-QS agent to mitigate membrane biofouling. Results demonstrated the occurrence of the N-acyl-homoserine-lactone (AHL) autoinducers (AIs), correlate QS activity and membrane biofouling mitigation. The AIs production in bioreactor was confirmed using an indicator strain Agrobacterium tumefaciens (NTL4) harboring plasmid pZLR4. Moreover, three different AHLs were found in biocake using thin layer chromatographic analysis. An increase in extracellular polymeric substances (EPS) and transmembrane pressure (TMP) was observed with AHL activity of the biocake during continuous MBR operation, which shows that membrane biofouling was in close relationship with QS activity. PBE was verified to mitigate membrane biofouling via inhibiting AIs production. SEM analysis further confirmed the effect of PBE on EPS and biofilm formation. These results exhibited that PBE could be a novel agent to target AIs for mitigation of membrane biofouling. Further work can be carried out to purify the active compound of Piper betle extract to target the QS to mitigate membrane biofouling.     

Growth stimulatory effect of Ochrobactrum intermedium and Bacillus cereus on Vigna radiata plants

AIMS: This study assessed the plant growth-promoting ability of the bacterial strains Ochrobactrum intermedium (isolate CrT-1) and Bacillus cereus (isolate S-6). METHODS AND RESULTS: Two chromium resistant bacterial strains isolated from chromium-contaminated wastewater and soils were identified as O. intermedium CrT-1 and B. cereus S-6. These strains were inoculated on seeds of mungbean Vigna radiata var NM-92, which were germinated and grown under chromate salts (300 microg ml(-1) of CrCl(3)or K(2)CrO(4)). The data show that Cr(VI) was more toxic because of its better availability to plants roots when compared with Cr(III). The major part of Cr(VI) supplied to the seedlings was reduced to Cr(III) in the rhizosphere by the bacterial strains, thus lowering the toxicity of chromium to seedlings. CONCLUSIONS: Strains have significant Cr(VI) resistance and reduction potential and have ability to enhance mungbean plant growth under chromium stress. SIGNIFICANCE AND IMPACT OF THE STUDY: These strains could be utilized for the growth of economically important cash crops as well as for the bioremediation of chromium-polluted soils.     

Influence of weather on the moth catches of Helicoverpa armigera at various cotton-based agro-ecological sites

Pheromones are innate products, exploited for direct population manipulation in the trapping of precise pest density. They demonstrate feasibility and efficiency against Helicopverpa armigera at five different cotton-based agro-ecological sites: river site, vegetable farm, orchard, clean cultivation site, and forest. The data were recorded at 15–20 day intervals from 8 September 2004 to 1 December 2006. The Number of moths caught during the study period demonstrated that the vegetable farm showed the maximum population of moths per trap (0.54), followed by the orchard (0.29), forest (0.19), river (0.15), and clean cultivation site (0.12). During 2004, rainfall (in the orchard and clean cultivation site) and relative humidity (in the clean cultivation site) showed positive and significant correlation with the number of moths caught. During 2005, temperatures played a significant and positive role in population fluctuation of the pest almost at all the selected sites; the minimum temperature was recorded at the vegetable farm and the average temperature was found at the forest site. Rainfall also showed a significant and positive correlation with trapped moths in the vegetable farm, orchard, and clean cultivation site. During 2006, relative humidity showed a significant and negative correlation with the trapped population at all the sites except the river site. Rainfall showed a negative and significant correlation with the pest at the forest site. Relative humidity was the most important aspect at 8.93% causing variation in the trapped population followed by maximum temperature (5.7%), rainfall (1.63%), average temperature (0.74%), and minimum temperature (0.56%).     

Seasonal distribution and species composition of daytime biting mosquitoes

Adults and immatures of Aedes mosquito populations were collected at temperatures between 40 and 44°C (summer), while larvae were collected at 0°C (winter). Major mosquito activities were observed from February to mid-December at various collection sites that yielded high populations of Aedes spp. from May to September, and high populations of Culex spp. and Anopheles spp. from March to September. In June to July, mosquito activity was suspended because the relative humidity was high (70%); a result of the monsoon rains. In August, with temperature ranging from 38 to 42°C, the populations of Culex , Anopheles and Aedes began to increase (36.8, 32.1 and 26.3%, respectively). Population estimates (through standard prototype Centers for Disease Control (CDC) and Biogents (BG)-sentinel) and species composition of Aedes in forest habitats indicated a rapid increase in the populations of Ae. albopictus (52.3%), Ae. aegypti (19.1%) and Ae. vittatus (28.5%) following the rainy season in July. Areas positive for Ae. albopictus had identical population levels and distribution ranges of Ae. vittatus , however, there were no Ae. aegypti in Ae. albopictus areas from August to September. The population level, seasonal distribution, habitat and areas of adult activity marked by global positioning system (GPS) coordinates are being used for reference and for species composition data of Anopheles spp. (2), Culex spp. (10) and Aedes spp. (5) in addition to associated temperature, relative humidity and physico-chemical factors of larval habitat. Global meteorological changes have caused an expansion of the active period, leading to the mosquito's possibility of being a vector of disease increasing, resulting in the spread of dengue fever.     

Modulation of Activation-Induced Cytidine Deaminase by Curcumin in Helicobacter pylori-Infected Gastric Epithelial Cells

Background: Anomalous expression of activation‐induced cytidine deaminase (AID) in Helicobacter pylori‐infected gastric epithelial cells has been postulated as one of the key mechanisms in the development of gastric cancer. AID is overexpressed in the cells through nuclear factor (NF)‐κB activation by H. pylori and hence, inhibition of NF‐κB pathway can downregulate the expression of AID. Curcumin, a spice‐derived polyphenol, is known for its anti‐inflammatory activity via NF‐κB inhibition. Therefore, it was hypothesized that curcumin might suppress AID overexpression via NF‐κB inhibitory activity in H. pylori‐infected gastric epithelial cells. Materials and Methods: MKN‐28 or MKN‐45 cells and H. pylori strain 193C isolated from gastric cancer patient were used for co‐culture experiments. Cells were pretreated with or without nonbactericidal concentrations of curcumin. Apoptosis was determined by DNA fragmentation assay. Enzyme‐linked immunosorbent assay was performed to evaluate the anti‐adhesion activity of curcumin. Real‐time polymerase chain reaction was employed to evaluate the expression of AID mRNA. Immunoblot assay was performed for the analysis of AID, NF‐κB, inhibitors of NF‐κB (IκB), and IκB kinase (IKK) complex regulation with or without curcumin. Results: The adhesion of H. pylori to gastric epithelial cells was not inhibited by curcumin pretreatment at nonbactericidal concentrations (≤10 μmol/L). Pretreatment with nonbactericidal concentration of curcumin downregulated the expression of AID induced by H. pylori. Similarly, NF‐κB activation inhibitor (SN‐50) and proteasome inhibitor (MG‐132) also downregulated the mRNA expression of AID. Moreover, curcumin (≤10 μmol/L) has suppressed H. pylori‐induced NF‐κB activation via inhibition of IKK activation and IκB degradation. Conclusion: Nonbactericidal concentrations of curcumin downregulated H. pylori‐induced AID expression in gastric epithelial cells, probably via the inhibition of NF‐κB pathway. Hence, curcumin can be considered as a potential chemopreventive candidate against H. pylori‐related gastric carcinogenesis.     

Pregnant Women in and Around Dhaka City: Are Their Children at Risk of Developing Congenital Rubella Syndrome?

Rubella Virus (RUBV) is a common cause of childhood rash and fever in non-immunized populations, and its public health importance relates to teratogenic effects of primary rubella infection in women with early pregnancy. Infection of the fetus may lead to congenital rubella syndrome (CRS). This work aimed to assess the degree of risk associated in acquiring rubella virus infection by the women during pregnancy and developing CRS among their children in Bangladesh. The study population (n = 275) included pregnant mothers (15–38 years) from various socioeconomic backgrounds attending a women health care based hospital. All subjects were personally interviewed, clinically examined and a standardized questionnaire was filled up for each of them. From each participant 3 ml blood was taken and serum was separated. Commercially available ELISA kit was used for the qualitative and quantitative determination of IgM and IgG class antibodies against RUBV in collected serum samples. 209 women were found to contain detectable level of antiRUBV IgG antibodies, but did not possess IgM antibodies against rubella. Only 9% participants were vaccinated previously against rubella virus among the whole antenatal population studied. Ninety-two percent of these vaccinated pregnant women contained serum anti-rubella IgG antibody which was significantly (P = 0.05) higher than that of the nonvaccinated study population (75%). Pregnant women from lower middle and poor socioeconomic class had significantly (P = 0.05) more intra uterine growth retardation (IUGR) of fetus than the upper middle class. 20% of the women of child bearing age examined in this work were not yet exposed to RUBV and at risk of acquiring this virus during pregnancy and subsequently transmitting the virus to the fetus. Our work demonstrates rubella attack rate among antenatal population in Bangladesh as 14.5 in 1000 during pregnancy. A proper and reliable vaccination policy against rubella virus is not yet adopted at the national level in many developing countries including Bangladesh. This work identifies the requirement of detailed study for the identification of intrauterine rubella infection and its related influence on perinatal morbidity and mortality. Thorough epidemiological studies are also considered necessary prior to the development and acceptance of national immunization program against rubella virus in Bangladesh.