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Sarcoids are the most commonly diagnosed skin tumours in equines. Bovine papillomaviruses (BPVs) are the primary causative agent of sarcoids. There has been intensive research to discover the molecular mechanisms that may contribute to the aetiopathogenesis of this disease and tumour suppressors and proto-oncogenes known to play a role in human neoplastic conditions have been investigated in equine sarcoids. Current approaches include the identification of gene expression profiles, characterising sarcoid and normal skin tissues, and an assessment of epigenetic alterations such as microRNA differential expression and DNA methylation status. This review focuses on selected groups of genes that contribute to the molecular mechanisms of sarcoid formation. These genes have the potential to complement current clinical examinations of equine sarcoid disease in diagnosis, prognosis, therapeutic response and screening.  相似文献   

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OBJECTIVE: To determine expression of a transforming gene (E5) of bovine papillomavirus in sarcoids, other tumors, and normal skin samples collected from horses with and without sarcoids. SAMPLE POPULATION: 23 sarcoids and 6 samples of normal skin obtained from 16 horses with sarcoids, 2 samples of normal skin and 2 papillomas obtained from horses without sarcoids, and 1 papilloma obtained from a cow. PROCEDURE: Protein was extracted from tissue samples collected from horses and incubated with agarose beads covalently coupled to Staphylococcus aureus protein A and an anti-E5 polyclonal antibody. Following incubation, proteins were eluted from the beads and electrophoresed on a 14% polyacrylamide gel and transferred to a polyvinylidene difluoride membrane. The E5 protein was detected by use of western blot analysis, using a chemiluminescence detection system. RESULTS: All 23 sarcoids had positive results for expression of E5 protein. Quantity of viral protein appeared to vary among sarcoids. All other tissues examined had negative results for E5 protein. Highest expression for E5 protein was observed in biologically aggressive fibroblastic variants of sarcoids, compared with expression in quiescent tumors. CONCLUSIONS AND CLINICAL RELEVANCE: This study documented that activation and expression of the E5 gene is evident in sarcoids obtained from horses. These data support the conclusion that infection with bovine papillomavirus is important in the initiation or progression of sarcoids in horses. Treatment strategies designed to increase immune recognition of virally infected cells are warranted.  相似文献   

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In pig, the histological profile of muscle tissue, especially the proportion of individual fiber types, is one of the main factors affecting meat quality properties. In the present research, RNA sequencing (RNA‐seq) by using next generation sequencing method was applied to estimate the whole gene expression profile of Longissimus lumborum muscle of pigs (Large White breed) differing in the percentage of two fiber types (slow‐twitch (type I) fibers and fast‐twitch glycolytic (type IIB) fibers). The RNA‐seq approach allowed us to identify 355 differentially expressed genes (DEGs) indicated as significant (false discovery rate‐adjusted P < 0.05) using three types of software: DESeq2, edgeR and baySeq. Detected genes and pathways deregulated in muscle depending on tissue microstructure were associated with: metabolic processes – 158 genes; cellular processes – 122; biological regulation – 62; localization – 51; and 35 genes with developmental processes. The DEGs were included in: PI3K‐Akt; FoxO and MAPK signaling pathways, regulation of actin cytoskeleton, lysine degradation and insulin signaling pathway as well as mTOR and Hippo signaling pathways. These results highlight the mainly metabolic pathways related to glucose metabolism and contraction processes of muscle cells. Detection of genes involved in variation of fiber‐type distribution will be useful in understanding of the genetic factors affecting muscle structure, metabolic process and indirectly, meat quality traits.  相似文献   

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Daidzein has been reported to be effective in regulating lipid metabolism in animals. However, the molecular mechanisms of daidzein on adipogenesis in beef cattle are not yet reported and the results of daidzein on affecting lipid metabolism in other species have been conflicting. High-throughput sequencing of mRNA (RNA-Seq) technology was performed to elucidate the underlying molecular mechanisms of daidzein on adipogenesis in subcutaneous adipose tissue of finishing Xianan beef cattle. A total of 893 differentially expressed genes (DEGs) were identified by differential expression analysis, among which 405 genes were upregulated and 488 genes were downregulated. Bioinformatics analysis suggested that these DEGs were significantly enriched to the pathways related to lipid metabolism including ECM–receptor interaction, Glycolysis/Gluconeogenesis and Hedgehog signalling pathway. Daidzein significantly affected the candidate genes (Shh, Pec, Gli, Wnt6, DLK, IGFBP2, ID3 and C/EBPE) related to adipocyte differentiation. Besides, daidzein improved the ability of subcutaneous adipocytes in synthesizing triglycerides by directly using the long-chain fatty acids and enhanced the efficiency of triglyceride synthesis of subcutaneous adipocytes in Xianan steers. In conclusion, daidzein plays a positive role not only in adipogenic differentiation, but also in triglyceride synthesis in subcutaneous adipose tissue of Xianan beef cattle.  相似文献   

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In human cancer cells, BAG3 protein is known to sustain cell survival. Here, for the first time, we demonstrate the expression of BAG3 protein both in equine sarcoids in vivo and in EqS04b cells, a sarcoid-derived fully transformed cell line harbouring bovine papilloma virus (BPV)-1 genome. Evidence of a possible involvement of BAG3 in equine sarcoid carcinogenesis was obtained by immunohistochemistry analysis of tumour samples. We found that most tumour samples stained positive for BAG3, even though to a different grade, while normal dermal fibroblasts from healthy horses displayed very weak staining pattern for BAG3 expression. By siRNA technology, we demonstrate in EqS04b the role of BAG3 in counteracting basal as well as chemical-triggered pro-death signals. BAG3 down-modulation was indeed shown to promote cell death and cell cycle arrest in G0/G1. In addition, we found that BAG3 silencing sensitized EqS04b cells to phenethylisothiocyanate (PEITC), a promising cancer chemopreventive/chemotherapeutic agent present in edible cruciferous vegetables. Notably, such a pro-survival role of BAG3 was less marked in E. Derm cells, an equine BPV-negative fibroblast cell line taken as a normal counterpart. Altogether our findings might suggest a mutual cooperation between BAG3 and viral oncoproteins to sustain cell survival.  相似文献   

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文章旨在研究绒山羊皮肤生物钟基因clock、tim、per1和cry1的表达模式,进而分析其在绒山羊皮肤组织中的作用及相互关系。生物钟基因形成一个转录-翻译反馈环,通过钟基因在绒山羊皮肤生长周期进行高表达,激活per1和cry1基因的转录-转化过程,从而在mRNA和蛋白水平的调控下进行有节律的表达。结果表明,这些生物钟基因在绒山羊皮肤中的表达量依次为:clocktimper1cry1;皮肤次级毛囊兴盛期,高振幅clock、per1、tim、cry1的节律表达分别出现在一天中的04∶00、08∶00、08∶00、16∶00;皮肤次级毛囊休止期,这些基因的高振幅节律表达分别出现在一天中的08∶00、04∶00、04∶00、16∶00。另外,cry1、per1基因的表达在生物钟基因正反馈循环中被激活,tim基因的表达在生物钟基因的负反馈循环中被激活。因此,clock、tim、per1和cry1调控下运行的钟基因反馈环是绒毛生长呈周期性现象的基础。  相似文献   

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To determine the causative variations associated with two chicken comb phenotypes, pendulous comb (PC) or upright comb (UC), two pooled genomic DNA samples from PC and UC chickens were re‐sequenced by Next‐Generation Sequencer, and genome‐wide Single nucleotide polymorphisms (SNPs) were detected. Using three selective sweep approaches, FST, θπ, and Tajima's D, with top 5% window values serving as the threshold, a total of 84 positively selective genes (PSGs) were identified. There were no SNPs in exons of the PSGs with significant differences in allele frequencies between the two comb phenotype groups. Then, 515 differentially expressed genes (DEGs) between the PC and UC were identified by RNA‐seq. Three genes including CD36 (CD36 molecule), ADAMTSL3 (ADAMTS‐like 3), and AOX1 (aldehyde oxidases 1) are overlapped between PSGs and DEGs. After genotyping seven candidate SNPs in the regulatory regions of the three overlapping genes in 120 chickens from two other breeds, two variants (rs14607046 and rs731818051) in the regulatory regions of AOX1 and ADAMTSL3 were found to have significant differences in allele frequency between the PC and UC, suggesting that the two variants may be causative mutations for PC. Overall, our study shed light on the genetic basis underlying the PC phenotype in chickens.  相似文献   

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OBJECTIVE: To determine the incidence of bovine papillomavirus (BPV) type 1 or 2 in sarcoids and other samples of cutaneous tissues collected from horses in the western United States. ANIMALS: 55 horses with sarcoids and 12 horses without sarcoids. PROCEDURE: Tissue samples (tumor and normal skin from horses with sarcoids and normal skin, papillomas, and nonsarcoid cutaneous neoplasms from horses without sarcoids) were collected. Tissue samples were analyzed for BPV-1 or -2 DNA, using a polymerase chain reaction (PCR) and restriction fragment length polymorphism. The PCR products from 7 sarcoid-affected horses were sequenced to evaluate percentage homology with expected sequences for BPV-1 or-2. RESULTS: Most (94/96, 98%) sarcoids contained BPV DNA. Sixty-two percent of the tumors examined had restriction enzyme patterns consistent with BPV-2. Thirty-one of 49 (63%) samples of normal skin obtained from horses with sarcoids contained BPV DNA. All samples subsequently sequenced had 100% homology with the expected sequences for the specific viral type. All tissues from healthy horses, nonsarcoid neoplasms, and papillomas were negative for BPV DNA. CONCLUSIONS AND CLINICAL RELEVANCE: Bovine papillomaviral DNA was detected in essentially all sarcoids examined. There appears to be regional variation in the prevalence of viral types in these tumors. The fact that we detected viral DNA in normal skin samples from horses with sarcoids suggests the possibility of a latent viral phase. Viral latency may be 1 explanation for the high rate of recurrence following surgical excision of sarcoids.  相似文献   

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In equids, bovine papillomaviruses of type 1 (BPV-1) and less frequently type 2 induce common, locally aggressive skin tumours termed sarcoids. Whereas BPV infection in cattle usually involves the epidermis and is productive in this skin layer, infection in equids is currently thought to be abortive, with virus solely residing as multiple episomes in dermal fibroblasts. Based on recent observations that do not agree with this assumption, we hypothesised that BPV also infects equid epidermis and is active in this skin layer. To test this hypothesis, we conducted a proof-of-principle study on eight distinct sarcoids. Presence of viral DNA was addressed by qualitative and quantitative BPV-1 PCR from microdissected sarcoid epidermis, and by subsequent amplicon sequencing. Viral activity was assessed by screening sarcoid epidermis for BPV-1 protein expression using immunohistochemistry (IHC) or immunofluorescence (IF). Virus-free equine skin served as negative control throughout the assays. BPV-1 DNA was demonstrated in all sarcoid epidermis samples, with viral DNA loads ranging between 2 and 195 copies/cell. Identical BPV-1 E5 genes were identified in epidermis and dermis of each of two sarcoids, yet different E5 variants were found in individual lesions. IHC/IF revealed the presence of E5 and E7 protein in sarcoid epidermis, and L1 capsomers in the squamous layer of one lesion. These findings indicate that BPV infection also involves the epidermis, where it may occasionally be productive.  相似文献   

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Spatial/temporal controls of development are regulated by the homeotic (HOX) gene complex and require integration with oncogenes and tumour suppressors regulating cell cycle exit. Spontaneously derived neoplastic canine mammary carcinoma cell models were investigated to determine if HOX expression profiles were associated with neoplasia as HOX genes promote neoplastic potential in human cancers. Comparative assessment of human and canine breast cancer expression profiles revealed remarkable similarity for all four paralogous HOX gene clusters and several unlinked HOX genes. Five canine HOX genes were overexpressed with expression profiles consistent with oncogene‐like character (HOXA1, HOXA13, HOXD4, HOXD9 and SIX1) and three HOX genes with underexpressed profiles (HOXA11, HOXC8 and HOXC9) were also identified as was an apparent nonsense mutation in HOXC6. This data, as well as a comparative analysis of similar data from human breast cancers suggested expression of selected HOX genes in canine mammary carcinoma could be contributing to the neoplastic phenotype.  相似文献   

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The purpose of the present study was to examine whether bovine papillomavirus (BPV) DNA can be detected on the normal skin and in the habitual surroundings of horses with and without equine sarcoids by means of superficially taken swabs. In affected horses, no significant difference in presence of BPV-DNA could be observed between samples obtained from the equine sarcoid surface, from normal skin close to the tumour and from a normal skin site in direct contact with the tumour. From the group of healthy horses living in contact with affected horses, 44% were BPV-DNA positive. The surroundings of affected and non-affected horses are probably not a major source of BPV-DNA contamination. It can be concluded that BPV-DNA is present on the normal skin of horses affected by equine sarcoid and to a lesser degree, on the normal skin of horses living in contact with affected horses.  相似文献   

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Reasons for performing study: Sarcoids are the commonest form of equine skin tumour. Several therapeutic measures have been described but none is considered to be universally effective. Electrochemotherapy (ECT) is a new anticancer therapy that utilises electrical field pulses to induce increased cell membrane permeability to antitumour hydrophilic drugs, such as cisplatin. The increased intracellular concentration of the drugs has a significant therapeutic benefit. The procedure has not been previously reported in a large number of horses. Objective: To validate ECT as a novel alternative treatment for equine sarcoids. Methods: A retrospective study evaluating the efficacy of cisplatin ECT in the treatment of equine sarcoids was performed. Electrochemotherapy treatments were applied under general anaesthesia at 2 week intervals with or without prior excision or debulking. Electric pulses were directly applied to the lesions following intra‐tumoural injections of an aqueous solution of cisplatin. Results: One‐hundred‐and‐ninety‐four sarcoids on 34 horses, 2 ponies, 11 donkeys and one mule were treated with ECT. The 4 year nonrecurrence rate was 97.9% for animals (47/48) and 99.5% (193/194) for tumours. When ECT was used as a single treatment, a significant influence of tumour size (ρ= 0.55) on the number of treatments required for cure was shown. When prior surgery was performed, there was a significant influence (P<0.001) of the excision quality (complete or incomplete) and the healing mode (closed or open wound) on the number of treatments. The most common adverse effect was a slight oedematous reaction for lesions located on thin skin regions. Conclusion and clinical relevance: Results demonstrate that ECT, with or without concurrent tumour debulking, is an effective alternative for treatment of equine sarcoids.  相似文献   

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