Nitric Oxide (NO) and Cyclooxygenase-2 (COX-2) Cross-Talk in Co-Cultures of Tumor Spheroids with Normal Cells

Cyclooxygenases (COX), prostaglandin E2 (PGE2) and nitric oxide (NO) are believed to be some of the most important factors related to colon cancer growth and metastasis. In this study, we aimed to investigate the associations between COX-2, PGE2 and NO in co-cultures of human colon cancer spheroids obtained from different tumor grades with normal human colonic epithelium and myofibroblast monolayers. L-arginine (2 mM), a substrate for nitric oxide synthases (NOS), decreased COX-2 and PGE2 levels, while NG-nitro-L-arginine methyl ester (L-NAME) (2 mM), a NOS inhibitor, had no influence on COX-2 and PGE2 levels but limited tumor cell motility. NS398 (75 μM), a selective COX-2 inhibitor, had no significant influence on NO level but decreased motility of tumor cells. COX-2, PGE2 and NO levels depended on the tumor grade of the cells, being the highest in Duke’s stage III colon carcinoma. Summing up, we showed that addition of L-arginine at doses which did not stimulate NO level caused a significant decrease in COX-2 and PGE2 amounts in co-cultures of colon tumor spheroids with normal epithelial cells and myofibroblasts. Any imbalances in NO level caused by exogenous factors influence COX-2 and PGE2 amounts depending on the kind of cells, their reciprocal interactions and the local microenvironmental conditions. The knowledge of these effects may be useful in limiting colon carcinoma progression and invasion

The role of the muscarinic system in regulating estradiol secretion varies during the estrous cycle: the hemiovariectomized rat model

There is evidence that one gonad has functional predominance. The present study analyzed the acute effects of unilateral ovariectomy (ULO) and blocking the cholinergic system, by injecting atropine sulfate (ATR), on estradiol (E(2)) serum concentrations during the estrous cycle. The results indicate that ULO effects on E(2 )concentrations are asymmetric, vary during the estrous cycle, and partially depend on the cholinergic innervation. Perforation of the left peritoneum resulted in lower E(2 )serum concentrations in the three stages of the estrous cycle. At proestrus, unilateral or bilateral perforation of the peritoneum resulted in lower E(2 )serum concentrations. ULO of the right ovary (left ovary in situ) resulted in significantly higher E(2 )concentrations than animals with ULO of the left ovary (right ovary in situ). ATR treatment to ULO rats on D1 resulted in a significant drop of E(2 )serum concentrations. ULO rats treated with ATR on D2 or P, resulted in an asymmetrical E(2) secretion response; when the right ovary remained in situ an increase in E(2) was observed, and a decrease when the left ovary remained in situ. The results obtained in the present study suggest that each ovary's ability to compensate the secretion of E(2 )from the missing ovary is different and varies during the estrous cycle. The results also suggest that the cholinergic system participates in regulating ovarian E(2 )secretion. Such participation varies according to the ovary remaining in situ and the stage of the estrous cycle of the animal. The results agree with previously stated hypothesis of a neural pathway arising from the peritoneum that participates in regulating E(2 )secretion, and also supports the idea of cross-talk between the ovaries, via a neural communication, that modulates E(2 )secretion

Amelioration effects against N-nitrosodiethylamine and CCl4-induced hepatocarcinogenesis in Swiss albino rats by whole plant extract of Achyranthes aspera

Objective: The prevalence of oxidative stress may be implicated in the etiology of many pathological conditions. Protective antioxidant action imparted by many plant extracts and plant products make them a promising therapeutic drug for free-radical-induced pathologies. In this study, we assessed the antioxidant potential and suppressive effects of Achyranthes aspera by evaluating the hepatic diagnostic markers on chemical-induced hepatocarcinogenesis. Materials and Methods: The in vivo model of hepatocarcinogenesis was studied in Swiss albino rats. Experimental rats were divided into five groups: control, positive control (NDEA and CCl 4 ), A. aspera treated (100, 200, and 400 mg/kg b.w.). At 20 weeks after the administration of NDEA and CCl 4 , treated rats received A. aspera extract (AAE) at a dose of 100, 200, and 400 mg/kg once daily route. At the end of 24 weeks, the liver and relative liver weight and body weight were estimated. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and reduced glutathione (GSH) were assayed. The hepatic diagnostic markers namely serum glutamic oxaloacetic transminase (AST), serum glutamic pyruvate transminase (ALT), serum alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), and bilirubin (BL) were also assayed, and the histopathological studies were investigated in control, positive control, and experimental groups. Results: The extract did not show acute toxicity and the per se effect of the extract showed decrease in LPO, demonstrating antioxidant potential and furthermore no change in the hepatic diagnosis markers was observed. Administration of AAE suppressed hepatic diagnostic and oxidative stress markers as revealed by decrease in NDEA and CCl 4 -induced elevated levels of SGPT, SGOT, SALP, GGT, bilirubin, and LPO. There was also a significant elevation in the levels of SOD, CAT, GPx, GST, and GSH as observed after AAE treatment. The liver and relative liver weight were decreased after treatment with AAE in comparison to positive control group. The architecture of hepatic tissue was normalized upon treatment with extract at different dose graded at 100, 200, and 400 mg/kg. b.w. in comparison to positive control group. Conclusion: These results suggest that A. aspera significantly alleviate hepatic diagnostic and oxidative stress markers which signify its protective effect against NDEA and CCl 4 -induced two-stage hepatocarcinogenesis

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Not AvailablePhosphorus (P) is an essential macronutrient to all crops including rice and it plays a key role in various plant activities and development. Low availability of P in the soils negatively, influences rice crop growth and causes significant yield loss. In the present study, we characterized a set of 56 germplasm lines for their tolerance to low soil P by screening them at low soil P and optimum soil P levels along with low soil P tolerant and sensitive check varieties. These lines were genotyped for the presence/absence of tolerant allele with respect to the major low soil P tolerance QTL, Pup1, using a set of locus specific PCR-based markers, viz., K46-1, K46-2, K52 and K46CG-1. High genetic variability was observed for various traits associated with low soil P tolerance. The yield parameters from normal and low soil P conditions were used to calculate stress tolerance indices and classify the genotypes according to their tolerance level. Out of the total germplasm lines screened, 15 lines were found to be tolerant to low soil P condition based on the yield reduction in comparison to the tolerant check, but most of them harbored the complete or partial Pup1 locus. Interestingly, two tolerant germplasm lines, IC216831 and IC216903 were observed to be completely devoid of Pup1 and hence they can be explored for new loci underlying low soil P tolerance.Council for Scientific and Industrial Research (CSIR), Government of IndiaICAR-Indian Institute of Rice Researc