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Boroushaki MT 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2003,136(4):367-375
Hexachlorobutadiene (HCBD) is a potent nephrotoxin in rodents that can cause degeneration, necrosis and regeneration in renal tubular epithelial cells. Its toxicity is due to its conjugation by glutathione (GSH) to form glutathione S-conjugate, by the enzyme glutathione S-transferase and finally to the related cysteine-conjugate. This metabolite is then actively taken up by kidney and cleared in the renal tubular epithelial cells, rich in beta-lyase, to a reactive thiol derivative that covalently binds to the macromolecules. In this study, different groups of 28-day male Wistar albino (W/A) rats were dosed daily with 25 mg/kg HCBD for 2, 3, 4 and 7 days; control group dosed with corn oil. Data showed that in the 2- and 3-day treated groups there was substantial necrosis to the straight portion of the proximal tubules (pars recta or S3 segment), rich in glutamine transaminase K (GTK/beta-lyase). In the 4-day treated group, the renal proximal tubules had regenerated and showed a basophilic appearance. In animals treated for 7 days, it was observed that the kidney appeared to have returned to normal and had become resistant to further doses of HCBD. To define the time for the kidney to regain susceptibility to HCBD, 18- and 25-day studies with both low (25 mg/kg) and high (100 mg/kg) doses of HCBD (following two initial doses of 25 mg/kg) were performed. In the 18-day study, histopathological examination of the kidneys in animals of this group and also animals in the 25-day study, which received two further doses of HCBD, showed that the severity of kidney damage is much less than in the 2-day treated animals, a clear indication that the tubular cells were still resistant to the low dose of HCBD. Concentration of blood urea nitrogen, as a marker of kidney damage, in these two groups also confirmed the results. In animals re-exposed to the high dose of HCBD, data showed that the susceptibility to HCBD was starting to return. 相似文献
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Jake K Nikota Fernando M Botelho Carla MT Bauer Manel Jordana Anthony J Coyle Alison A Humbles Martin R Stampfli 《Respiratory research》2011,12(1):39
Background
While the presence of the chitinase-like molecule YKL40 has been reported in COPD and asthma, its relevance to inflammatory processes elicited by cigarette smoke and common environmental allergens, such as house dust mite (HDM), is not well understood. The objective of the current study was to assess expression and function of BRP-39, the murine equivalent of YKL40 in a murine model of cigarette smoke-induced inflammation and contrast expression and function to a model of HDM-induced allergic airway inflammation.Methods
CD1, C57BL/6, and BALB/c mice were room air- or cigarette smoke-exposed for 4 days in a whole-body exposure system. In separate experiments, BALB/c mice were challenged with HDM extract once a day for 10 days. BRP-39 was assessed by ELISA and immunohistochemistry. IL-13, IL-1R1, IL-18, and BRP-39 knock out (KO) mice were utilized to assess the mechanism and relevance of BRP-39 in cigarette smoke- and HDM-induced airway inflammation.Results
Cigarette smoke exposure elicited a robust induction of BRP-39 but not the catalytically active chitinase, AMCase, in lung epithelial cells and alveolar macrophages of all mouse strains tested. Both BRP-39 and AMCase were increased in lung tissue after HDM exposure. Examining smoke-exposed IL-1R1, IL-18, and IL-13 deficient mice, BRP-39 induction was found to be IL-1 and not IL-18 or IL-13 dependent, while induction of BRP-39 by HDM was independent of IL-1 and IL-13. Despite the importance of BRP-39 in cellular inflammation in HDM-induced airway inflammation, BRP-39 was found to be redundant for cigarette smoke-induced airway inflammation and the adjuvant properties of cigarette smoke.Conclusions
These data highlight the contrast between the importance of BRP-39 in HDM- and cigarette smoke-induced inflammation. While functionally important in HDM-induced inflammation, BRP-39 is a biomarker of cigarette smoke induced inflammation which is the byproduct of an IL-1 inflammatory pathway. 相似文献15.
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Development and characterization of highly polymorphic long TC repeat microsatellite markers for genetic analysis of peanut 总被引:4,自引:0,他引:4
Selma E Macedo Márcio C Moretzsohn Soraya C M Leal-Bertioli Dione MT Alves Ediene G Gouvea Vania CR Azevedo David J Bertioli 《BMC research notes》2012,5(1):1-10
Background
The immune system has paradoxical roles during cancer development and the prognostic significance of immune modulating factors is controversial. The aim of this study was to determine the expression of cyclooxygenase 2 (COX-2), transforming growth factor-beta (TGF- beta), interleukin-10 (IL-10) and their prognostic significance in breast cancers. Ki67 was included as a measure of growth fraction of tumor cells.Methods
On immunohistochemical stained slides from 38 breast cancer patients, we performed digital video analysis of tumor cell areas and adjacent tumor stromal areas from the primary tumors and their corresponding lymph node metastases. COX-2 was recorded as graded staining intensity.Results
The expression of TGF-beta, IL-10 and Ki67 were recorded in tumor cell areas and adjacent tumor stromal areas. In both primary tumors and metastases, the expression of COX-2 was higher in the tumor stromal areas than in the tumor cell areas (both P < 0.001). High stromal staining intensity in the primary tumors was associated with a 3.9 (95% CI 1.1-14.2) times higher risk of death compared to the low staining group (P = 0.036). The expression of TGF-beta was highest in the tumor cell areas of both primary tumors and metastases (both P < 0.001). High stromal expression of TGF-beta was associated with increased mortality. For IL-10, the stromal expression was highest in the primary tumors (P < 0.001), whereas in the metastases the expression was highest in tumor cell areas (P < 0.001). High IL-10 expression in tumor- and stromal cell areas of primary tumors predicted mortality. Ki67 was higher expressed in tumor stromal areas of the metastases, and in tumor cell areas of the primary tumors (P < 0.001). Ki67 expression in tumor cell areas and stromal areas of the metastases was independently associated with breast cancer mortality.Conclusions
Stromal expression of COX-2, TGF-beta and Ki67 may facilitate tumor progression in breast cancer. 相似文献17.
Ewa Przybytkowski Elizabeth Lenkiewicz Michael T Barrett Kathleen Klein Sheida Nabavi Celia MT Greenwood Mark Basik 《BMC genomics》2014,15(1)
Background
Chromosomal breakage followed by faulty DNA repair leads to gene amplifications and deletions in cancers. However, the mere assessment of the extent of genomic changes, amplifications and deletions may reduce the complexity of genomic data observed by array comparative genomic hybridization (array CGH). We present here a novel approach to array CGH data analysis, which focuses on putative breakpoints responsible for rearrangements within the genome.Results
We performed array comparative genomic hybridization in 29 primary tumors from high risk patients with breast cancer. The specimens were flow sorted according to ploidy to increase tumor cell purity prior to array CGH. We describe the number of chromosomal breaks as well as the patterns of breaks on individual chromosomes in each tumor. There were differences in chromosomal breakage patterns between the 3 clinical subtypes of breast cancers, although the highest density of breaks occurred at chromosome 17 in all subtypes, suggesting a particular proclivity of this chromosome for breaks. We also observed chromothripsis affecting various chromosomes in 41% of high risk breast cancers.Conclusions
Our results provide a new insight into the genomic complexity of breast cancer. Genomic instability dependent on chromosomal breakage events is not stochastic, targeting some chromosomes clearly more than others. We report a much higher percentage of chromothripsis than described previously in other cancers and this suggests that massive genomic rearrangements occurring in a single catastrophic event may shape many breast cancer genomes.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-579) contains supplementary material, which is available to authorized users. 相似文献18.
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Arezoo Rajabian Hamid Reza Sadeghnia Azar Hosseini Seyed Hadi Mousavi Mohammad Taher Boroushaki 《Journal of cellular biochemistry》2020,121(2):1778-1789
3-Acetyl-11-keto-β-boswellic acid (AKBA), a pentacyclic triterpenic acid present in gum resin of Boswellia serrata, has been found to possess antioxidant and neuroprotective properties. In this study, we aimed to examine protective properties of AKBA against glutamate-induced neuronal injury. To investigate the effects of AKBA (2.5-10 µM) on glutamate injury in neuron-like cells PC12 and N2a, two treatment regimens (incubation for 2 or 0 hours before glutamate exposure) were used. Then, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method was used to determine viability of the cells. Cellular redox status was evaluated using fluorimetry and comet assays. Annexin V/propidium iodide double staining and Western blot analysis of relative apoptotic proteins were conducted. Based on the results, 24 hours incubation with glutamate (8 mM) increased the cell mortality of PC12 and N2a (P < .001). However, AKBA (2.5-10 µM) enhanced the cell viability in both treatment regimens (P < .001). Also co- and pretreatment with AKBA significantly attenuated lipid peroxidation, reactive oxygen species production, and DNA injury (P < .05 and P < .001). AKBA also restored the activity of cellular superoxide dismutase under glutamate toxicity; this effect was seen to be more significant during the pretreatment regimen (P < .001). Moreover, Western blot analysis indicated that AKBA inhibited glutamate-induced programmed cell death through depressing the elevation of the expression ratio of Bax/Bcl-2 and cleaved-caspase-3 proteins, concentration-dependently. Overall, the present findings suggest the neuroprotective activities of AKBA against glutamate-induced cell injury probably by inhibiting oxidative damage and reducing apoptotic cell death. 相似文献