Gastrin-releasing peptide (GRP) is typically viewed as a growth factor in cancer. However, we have suggested that in colon cancer, GRP acts primarily as a morphogen when it and its receptor (GRP-R) are aberrantly upregulated. As such, GRP/GRP-R act(s) primarily to modulate processes contributing to the assumption or maintenance of tumor differentiation. One of the most important such processes is the ability of tumor cells to achieve directed motility in the context of tissue remodeling. Yet the cellular conditions affecting GRP/GRP-R expression, and the biochemical pathways involved in mediating its morphogenic properties, remain to be established. To study this, we evaluated the human colon cancer cell lines Caco-2 and HT-29 cells. We found that confluent cells do not express GRP/GRP-R. In contrast, disaggreation and plating at subconfluent densities results in rapid GRP/GRP-R upregulation followed by their progressive decrease as confluence is achieved. GRP/GRP-R coexpression correlated with that of focal adhesion kinase (FAK) phosphorylation of Tyr(397), Tyr(407), Tyr(861), and Tyr(925) but not Tyr(576) or Tyr(577). To more specifically evaluate the kinetics of GRP/GRP-R upregulation, we wounded confluent cell monolayers. At t = 0 h GRP/GRP-R were not expressed, yet cells immediately began migrating into the gap created by the wound. GRP/GRP-R were first detected at approximately 2 h, and maximal levels were observed at approximately 6 h postwounding. The GRP-specific antagonist [d-Phe(6)]-labeled bombesin methyl ester had no effect on cell motility before GRP-R expression. In contrast, this agent increasingly attenuated cell motility with increasing GRP-R expression such that from t = 6 h onward no further cell migration into the gap was observed. Overall, these findings indicate the existence of GRP-independent and -dependent phases of tumor cell remodeling with the latter mediating colon cancer cell motility during remodeling via FAK.
Protecting the water resources will be a formidable challenge in the study area, which requires modernization of tannery industry, thereby improving the recovery and recycling of TW. Moreover, PIXE analysis presented here as a successful tool, could serve as landmark for the contemporary research in environmental toxicology.
The hepatoprotective effects of a Foeniculum vulgare extract was determined in male rabbits (Oryctolagus cuniculus). The Foeniculum vulgare extract was used in different doses in Paracetamol induced toxicity in rabbits. Foeniculum vulgare seeds were obtained from market and identified by Punjab University. Extract was prepared by maceration method. Foeniculum vulgare seeds 100 gm were weighed after grinding then added in flask. 80% ethanol solution was added four times more than the weight of Foeniculum vulgare powder and then kept for 4 days on shaker and filtered through Whatman filter paper. Solvent extract was evaporated at temperature of 25°C. Extract powder was obtained. Powder extract 250 mg/kg/BW and 500 mg/kg/BW was filled in capsule of 2 & 0 size respectively. 16 rabbits, with an average age of 3-4 months, were taken. They were provided standard diet and water. Animals were kept at light/dark cycle (12/12 h) at a temperature (25 ± 2°C) and relative humidity (60 ± 5%). Animals were kept at Laboratory environment for one week. Study designed animal were divided randomly into 4 group, having 4 animal in each group. Group A served as positive control, given no medicine. Group B was intoxicated with a single dose of Paracetamol (Par-cm) 2 g/kg per oral (P.O.) using carboxymethyl cellulose (CMC) 1% as a vehicle. Group C received Foeniculum vulgare seeds hydroalcoholic extract (250 mg/Kg) P.O. daily for 9 days, followed by a single dose of Paracetamol 2 g/kg P.O. on 9th day using carboxymethyl cellulose 1% as a vehicle. Group D was pretreated with Foeniculum vulgare seeds hydroalcoholic extract (500 mg /Kg) P.O. for 9 days, and then a single dose of Paracetamol 2 g/kg P.O. on 9 th day using carboxymethyl cellulose 1% as a vehicle. Animals were slaughtered after 24 hours of the last treatment. Blood and liver sample were collected from all controlled and treated rabbits for Liver Function Tests and Histopathological studies. Serum Liver enzymes AST (Aspartate Aminotransferase), ALT (Alanine Aminotransferase), ALP (Alkaline Phosphatase) and bilirubin were used as indicators to monitor the status of the liver either healthy or damaged. Serum liver enzymes and bilirubin level increased in Group B as compared to Group A. The values of indicators were almost decreased in Group C and Group D. Histopathological studies were used for further confirmation of biochemical analysis. Histopathological study of Group A showed a normal hepatic cell structure. While Group B showed sinusoids congestion and ballooning degeneration. These parameters were found mild and moderate in Group C and Group D. These histopathological findings also supported the biochemical results. Thus the study concluded that the Foeniculum vulgare extract was effective against Paracetamol induced toxicity in rabbits.
Introduction: Motor-function modulation through Pyridine-3-carboxylic acid was assessed against. Haloperidol induced Parkinson’s disease (PD) in albino-mice. The objectives of this study were to test the effect of Haloperidol in development of PD, effectiveness of Pyridine-3-carboxylic acid in mice and evaluation of the motor-function changes in mice before and after treatment.
Methods: The study was divided into 3 phases: During Phase-I (randomization), all the subjects were randomly divided into 4 groups and trained for wire-hanging, grip strength, vertical rod and swim tests for 1 week. During Phase-II (disease induction), PD was induced by intra-peritoneal (ip) administration of Haloperidol (HP) in a dose of 1 mg/kg/d for 7 days. Group-A comprised of healthy controls, Group-B (Diseased), Group-C (HP+Pyridine-3-carboxylic acid 7.15 mg/kg/d) and Group-D (HP+Pyridine-3-carboxylic acid15 mg/kg/d).
Results: Pyridine-3-carboxylic acid treatment continued for 5 weeks. During Phase-III the above mention tests were performed and the effects of Pyridine-3-carboxylic acid were recorded. However, in swim test Group D is statistically insignificant as compared to Group B (p=0.284). In recent study, haloperidol is found to be effective in inducing motor function anomalies likewise in Parkinson’s disease including movement slowness, difficulties with gait and balance.
Conclusion: oral administration of Pyridine-3-carboxylic acid improved Motor-function changes in diseased mice. Therefore, it is concluded that Pyridine-3-carboxylic acid may help to alleviate PD symptoms.
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