BackgroundIntegrins are used as prognostic indicators in breast cancer. Following engagement with extracellular matrix proteins, their signaling influences numerous cellular processes including migration, proliferation, and death. Integrin signaling varies between cell types through differential expression of integrin subunits, and changes within a given cell upon exposure to a cell agonist or through changes in its surroundings. These variations in signaling can profoundly affect the phenotypic, tumorogenecity and metastatic properties of cancer cells. In the present study, we investigated if there were differences in the expression of integrins, integrin structures, and integrin co-receptors within three breast cancer cells and if these differences effected integrin signaling.MethodsExpression of integrins, urokinase receptor and vascular endothelial cell growth factor receptor (VEGFR) in metastatic MDA-MB-435 and MDA-MB-231, non-metastatic MCF7 and non-breast cancer Hek-293 cells was measured by flow cytometry. Cell adhesion was assessed using collagen, fibrinogen, fibronectin and vitronectin coated plates. Changes in kinase levels following PMA stimulation, and cell adhesion-induced activation of kinases were determined by western blot analysis. Distribution of actin stress fibers and focal adhesions was assessed by immunocytochemistry.ResultsAll cells expressed αv integrins, while high β5 and αvβ5 expression was restricted to the cancer cells and high β3 and αvβ3 expression was restricted to MDA-MB-435 cells. The two metastatic cells were the least adhesive, but all cells adhered well to most proteins in the absence of PMA. All proliferating cells expressed activated pSrc, but only proliferating metastatic cells expressed high pMEK levels. PMA treatment resulted in time-dependent changes in activated kinase levels, and only MDA-MB-231 cells constitutively expressed high levels of activated pMEK. MDA-MB-435 cells formed more stress fibers and focal adhesions and only exhibited adhesion-induced activation of pMEK and pFAK. All cells expressed the urokinase receptor, but MCF7 cells had markedly higher VEGFR expression. Adhesion induced differential expression of pFAK, pMEK and pERK.ConclusionsThis study demonstrates that breast cancers vary in their expression of integrins, their capacity to form focal adhesion and to signal through integrins. These differences likely contribute to phenotypic variations between cancer lines and account for some of the heterogeneity of breast cancer.
Aims/IntroductionOxidative stress has a key role in the pathogenesis of diabetes. Propolis and its constituents have a wide range of medicinal properties against oxidative stress. In the present study, we evaluated the anti‐oxidant effects of ethanolic extracts of propolis on kidneys in diabetes mellitus rats.Materials and MethodsA total of 40 male Wistar rats were randomly divided into the following five groups: control, diabetes mellitus, diabetes mellitus with vehicle treatment, diabetes mellitus with propolis treatment (100 mg/kg) and diabetes mellitus with propolis treatment (200 mg/kg). Diabetes mellitus in rats was induced by intraperitoneal injection of streptozotocin (60 mg/kg). Diabetic groups were treated with vehicle or ethanolic extracts of Iranian propolis for 6 weeks. Serum concentration of malondialdehyde, superoxide dismutase and glutathione peroxidase were measured.ResultsThe results showed that Iranian propolis significantly inhibited bodyweight loss in diabetes mellitus rats. The propolis extracts significantly reduced serum glucose levels and kidney weight in diabetes mellitus rats (P < 0.001). Furthermore, propolis extracts significantly reduced the malondialdehyde content, and increased the activity of superoxide dismutase and glutathione peroxidase (P < 0.001) along with the total anti‐oxidant activity in the kidney tissue of diabetes mellitus rats. In the kidneys of the diabetes mellitus and vehicle group, the glomerular basement membrane thickness and glomerular area were significantly increased. Treatment of diabetes mellitus rats with the propolis extract significantly reduced the glomerular basement membrane thickness and glomerular area.ConclusionsThe present study results showed that the Iranian propolis extract could enhance the anti‐oxidant levels and histopathological changes in the kidneys of rats. The final results showed that most of the favorable effects of propolis are mediated by a reduction of blood glucose levels in diabetic animals.
Decreasing the side effects of chemotherapy in testis has been the subjects of many studies. In this study, the protective effects of Zingiber officinale extract on rat testis were investigated after chemotherapy with cyclophosphamide. Histological and biochemical parameters were compared in cyclophosphamide-treated rats with or without ginger extract intake. Wistar male rats were randomly divided into four groups each 10. The control group received a single injection of 1 ml isotonic saline intraperitoneally. The Cyclophosphamide (CP) group received a single dose of cyclophosphamide (100 mg kg(-1) BW) intraperitoneally. CP + 300 and CP + 600 groups received orally 300 or 600 mg of ginger extract, respectively, for a period of 6 weeks after cyclophosphamide injection. The morphologic and histological structure of the testis was compared in different groups of the rats. Also, factors like malondialdehyde, reactive oxygen species, total antioxidant capacity and testosterone level were assessed in blood serum as well. Our results showed that although ginger extract could not change testis weight, malondialdehyde (MDA) and ROS, but antioxidant and testosterone levels in serum were increased significantly. Also, an obvious improved histological change was seen in CP + 300 and CP + 600 groups in comparison with CP group. These protective effects of ginger on rat testis after cyclophosphamide treatment could be attributed to the higher serum level of antioxidants.
Cadaver dissection stands as a crucial component in medical curricula around the world, although computer-based multimedia programs have been introduced in order to replace the need for cadaver donations. Due to a decrease in the number of unclaimed bodies and rather few donations, there is an insufficient number of cadavers for anatomical studies in Iran. This study was carried out to evaluate medical students' awareness and willingness regarding body donation in Kashan University of Medical Sciences, Iran. In this study, a questionnaire was designed to focus on the cultural acceptability and personal willingness to donate one's body after death. Students from the university's anatomy classes (n = 331) participated in this study. Seventy-seven percent of the students expressed their agreement toward the idea of utilizing body donation services, though only 25.4% of participants were willing to donate their own bodies. None of the demographic factors were associated with cultural acceptability or personal willingness towards body donation. These findings indicated that besides "payment", other factors were associated with students' willingness to become donors. All factors of awareness except "previous awareness of organization" were associated with cultural acceptability. In this study, students suggested that encouraging people to register for body donation using mass media (25.6%) and teaching students to respect cadavers in the dissection environment (24.8%) were the best solutions for addressing the lack of cadavers. These findings indicated that a lack of awareness about body donation might be the main factor responsible for unwillingness towards body donation; therefore, improving the public's awareness and addressing the willingness of students regarding body donation may help overcome the current lack of donated cadavers. Anat Sci Educ 10: 120-126. © 2016 American Association of Anatomists.
Hsp90 chaperone complexes function in assembly, folding, and activation of numerous substrates. The 2 vertebrate homologues encoded by the genes hsp90a and hsp90b are differentially expressed in embryonic and adult tissues and during stress; however, it is not known whether they possess identical functional activities in chaperone complexes. This question was addressed by examining potential differences between the Hsp90 isoforms with respect to both cochaperone and substrate interactions. Epitope-tagged proteins were expressed in mammalian cells or Xenopus oocytes and subjected to immunoprecipitation with an array of co-chaperones. Both isoforms were shown to participate equally in multichaperone complexes, and no significant differences in cochaperone distribution were observed. The substrates Raf-1, HSF1, Cdc37, and MEK1 interacted with both Hsp90alpha and Hsp90beta, and the relative patterns of these interactions were not affected by heat shock. The substrate kinases c-Src, CKIIB, A-raf, and Erk interacted with both isoforms; however, significantly more Hsp90alpha was recovered after heat shock. The data demonstrate that Hsp90alpha and Hsp90beta exhibit similar interactions with co-chaperones, but significantly different behaviors with respect to substrate interactions under stress conditions. These results reveal both functional similarities and key functional differences in the individual members of this protein family.
Rosa canina L. (Rosaceae) has been traditionally used as a medicinal plant. This study was undertaken to evaluate the antidiabetic and antihyperlipidemic effects of Rosa canina fruit extract in streptozotocin induced diabetic rats. The results showed oral administration of Rosa canina fruit extract significantly ameliorated the high levels of blood glucose compared with the control group. Serum triglyceride levels significantly decreased by the administration of Rosa canina extract compared with control. Histopathological examinations showed that the Rosa canina extract improved islets necrotic and regenerated pancreatic islet cells. Rosa canina extract has the antihyperglycemic and antihyperlipidemic effects in streptozotocin-induced diabetic rats.
In this investigation, the effect of Matricaria chamomilla extract on linear incisional wound healing was studied. Thirty male Wistar rats were subjected to a linear 3 cm incision made over the skin of the back. The animals were randomly divided into three experimental groups, as control, olive oil, and treatment. Control group did not receive any drug or cold cream. Olive oil group received topical olive oil once a day from beginning of experiments to complete wound closure. Treatment group were treated topically by M. chamomilla extract dissolved in olive oil at the same time. For computing the percentage of wound healing, the area of the wound measured at the beginning of experiments and the next 2, 5, 8, 11, 14, 17, and 20 days. The percentage of wound healing was calculated by Walker formula after measurement of the wound area. Results showed that there were statistically significant differences between treatment and olive oil animals (p < 0.05) in most of the days. We conclude that the extract of M. chamomilla administered topically has wound healing potential in linear incisional wound model in rats.
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