Increased metastasis and a precipitous recurrence contribute to the lethality of ovarian cancer (OC). Several molecular mechanisms including aberrant-splicing have been closely associated with the extent of cancer progression. Numerous gene transcripts are differentially spliced in cancer cells, CD44 being one of them. CD44 splice isoforms contribute to the aggressiveness and gain of stem-like properties in different cancer types, but their role in ovarian cancer remains to be elucidated. We observed augmented CD44 levels in human ovarian cancer patient samples correlated with enhanced expression of the mesenchymal spliced variant CD44s (standard) and a concurrent decrease in the epithelial variants (CD44v). Moreover, CD44s was upregulated upon TGFβ1-induced EMT, which was mediated through the downregulation of the splicing factor, ESRP1. Furthermore, overexpression of this mesenchymal isoform in the OC cells induced EMT and invasion, followed by the gain of stem-like characteristics and chemoresistance. Since all these phenomena render lethality to this disease type, CD44s can be attributed for playing a major role in deregulated-splicing mediated ovarian cancer progression.
Summary The healing activity of the ethanol extracts of Piper betel, Emblica officinalis, Terminalia bellerica, and Terminalia chebula against the indomethacin-induced stomach ulceration has been studied and compared with that of misoprostol. Compared to autohealing, all the drugs accelerated the healing process, albeit to different extents. The relative healing activities of the extracts was P. betel>E. officinalis>T. bellerica~T. chebula, that correlated well with their in vivo antioxidant and mucin augmenting activities. The excellent healing activity of the extracts of P. betel and E. officinalis indicated a major role of mucin protection and regeneration in the healing of nonsteroidal anti-inflammatory drugs mediated stomach ulceration.
Gram-negative bacteria are inherently impermeable to hydrophobic compounds, due to the synergistic activity of the permeability barrier imposed by the outer membrane and energy dependent efflux systems. The gram-negative, enteric pathogen Vibrio cholerae appears to be deficient in both these activities; the outer membrane is not an effective barrier to hydrophobic permeants, presumably due to the presence of exposed phospholipids on the outer leaflet of the outer membrane, and efflux systems are at best only partially active. When V. cholerae was grown in the presence of bile, entry of hydrophobic compounds into the cells was significantly reduced. No difference was detected in the extent of exposed phospholipids on the outer leaflet of the outer membrane between cells grown in the presence or absence of bile. However, in the presence of energy uncouplers, uptake of hydrophobic probes was comparable between cells grown in the presence or absence of bile, indicating that energy-dependent efflux processes may be involved in restricting the entry of hydrophobic permeants into bile grown cells. Indeed, an efflux system(s) is essential for survival of V. cholerae in the presence of bile. Expression of acrAB, encoding an RND family efflux pump, was significantly increased in V. cholerae cells grown in vitro in the presence of bile and also in cells grown in rabbit intestine.Vibrio cholerae, a noninvasive enteric bacterium, is the causative agent of the diarrheal disease cholera. Cholera remains a major cause of human mortality in developing countries, where conditions of poor sanitation, war, famine, and malnourishment contribute to regular episodes of cholera epidemics. For successful infection of its human host, V. cholerae must colonize the small intestine and produce copious amounts of cholera toxin (CT), a potent enterotoxin that causes the massive fluid loss characteristic of the disease. In addition to obvious virulence factors like CT, other toxins, toxin-coregulated pilus, hemolysins, and hemagglutinins (factors essential for survival of the bacteria in vivo and evasion of the host defense system) also contribute to the pathogenecity of V. cholerae (for a review, see references 12 and 24).Enteric pathogens and normal intestinal flora must necessarily survive and colonize the intestine in the presence of bile. Bile salts are surface-active, amphipathic compounds with pronounced detergent-like activity that can cause disaggregation of the lipid bilayer structure of cellular membranes (11). However, gram-negative enteric bacteria are inherently resistant to bile, partly due to the basic, asymmetric structure of their outer membranes (OMs). Although the inner surface of the OM contains phospholipids, a characteristic lipopolysaccharide (LPS) is present on the outer leaflet that significantly retards diffusion of hydrophobic compounds across the OM. The OM thus functions as an effective permeability barrier and gives protection to enteric bacteria from potentially noxious agents present in the intestine, particula...
The purpose of the present research is to identify the trends in the concentrations of few atmospheric pollutants and meteorological parameters over an urban station Kolkata (22° 32' N; 88° 20' E), India, during the period from 2002 to 2011 and subsequently develop models for precise forecast of the concentration of the pollutants and the meteorological parameters over the station Kolkata. The pollutants considered in this study are sulphur dioxide (SO2), nitrogen dioxide (NO2), particulates of size 10-μm diameters (PM10), carbon monoxide (CO) and tropospheric ozone (O3). The meteorological parameters considered are the surface temperature and relative humidity. The Mann-Kendall, non-parametric statistical analysis is implemented to observe the trends in the data series of the selected parameters. A time series approach with autoregressive integrated moving average (ARIMA) modelling is used to provide daily forecast of the parameters with precision. ARIMA models of different categories; ARIMA (1, 1, 1), ARIMA (0, 2, 2) and ARIMA (2, 1, 2) are considered and the skill of each model is estimated and compared in forecasting the concentration of the atmospheric pollutants and meteorological parameters. The results of the study reveal that the ARIMA (0, 2, 2) is the best statistical model for forecasting the daily concentration of pollutants as well as the meteorological parameters over Kolkata. The result is validated with the observation of 2012.
Ovarian cancer (OC) is the fourth most common gynecological malignancy due to its highly aggressive, recurrent, and drug-resistant nature. The last two features are rendered by the presence of cancer stem cells (CSCs). Factors like TGFβ1 and their downstream signaling pathways are upregulated in most cancers and are known to induce EMT and stemness, but the exact mechanisms underlying the process remain unelucidated. In our study, TGFβ1 induced enhanced stem-like properties like high expression of the pluripotent markers SOX2, OCT4a, and NANOG, along with CD44, and CD117 in the OC cells. In addition, increased activity of the aldehyde dehydrogenase enzyme, formation of compact spheroids, and a quiescent phenotype were observed. In deciphering the mechanism behind it, our data propose ZEB1 transcription factor to play a substantial role in inducing the EMT-mediated stemness and chemoresistance. Further, in our study, we elucidated the significant contribution of both Smad and non-Smad pathways like ERK, JNK, and P38 MAPK pathways in the induction of stem-like characteristics. The novelty of the study also resides with the fact in the expression of different lineage-specific markers, like CD31, CD45, and CD117 along with CD44 in the TGFβ1-induced epithelial ovarian cancer spheroids. This suggests a tendency of the spheroidal cells towards differentiating into heterogenic populations, which is a distinctive feature of a stem cell. Taken together, the present study provides an insight to the molecular cues involved in the acquisition of stemness and chemoresistance along with tumor heterogeneity in TGFβ1-induced OC cells.
Oral administration of ethanol extract of the rhizome of Pirothiza kurroa at a dose,of 20mg/kg body weight, for 10 consecutive days , was found to enhance the rate of healing on Indomethacin-induced gastric ulcer in rats . compared to the ulcerated group without treatment.The level of peroxidised lipid ,in terms of thiobarbituric acid reactive species (TBARS), in gastric tissue, was increased in ulcerated rats which was restored to near normalcy on treatment with ethanol extract. The specific activity of in wvo antioxidant enzymes, viz SOD and catalase and total tissue sulfhydryl (thiol) group ,which were markedly decreased in ulcerated group ,were found to be significantly elevated (p< 0.05), on treatment with the above extract, at the specified dose ,compared to the indomethacin -induced ulcerated group without any supporting treatment. The present study thus suggests that the ethanol extract of rhizome of Picrorhiza kurroa, at the dose of 20mg/kg body weight, accelerated the healing of stomach wall of indomethacin induced gastric ulcerated rats by an in vivo free radical scavenging action.
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