The role of expression and activity of 15-Lipoxygenase isoforms and related cytokines in patients with Multiple Sclerosis and healthy controls

Safizadeh, Banafsheh; Hoshyar, Reyhane; Mehrpour, Masoud; Eftekhar, Mehrdad; Salimi, Vahid; Yazdani, Shaghayegh; Bijari, Bita; Khodakhah, Farshad; Tavakoli-Yaraki, Masoumeh

doi:10.1016/j.jneuroim.2018.10.009

Cited by 11 publications

(6 citation statements)

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“…Despite extensive efforts, the molecular mechanisms underlying pituitary tumor pathogenesis is uncertain and has yet to be determined [26]. Recently, the involvement of bioactive lipids and arachidonic acid-related mediators in regulating diseases outcomes likewise diabetes mellitus [27], autoimmune diseases [17], asthma [14] and aging [28] has been attended. Moreover, the aberrant lipid signaling and metabolism considered as a hallmark of different types of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Recent evidences provided insights into the implication of 15-Lox enzymes and mediators in pathogenesis of multiple diseases including asthma [14], viral infection [15], arthritis [12], cardiovascular diseases [16], autoimmune diseases [17] and cancer [18]. Recently, 15-Lox pathway has attained remarkable interests for its involvement in different cancer cell growth, proliferation, death and development [19].…”

Section: Introductionmentioning

confidence: 99%

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Up-regulation of 15-lipoxygenase enzymes and products in functional and non-functional pituitary adenomas

et al. 2019

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Background Pituitary adenoma accounts as a complex and multifactorial intracranial neoplasm with wide range of clinical symptoms which its underlying molecular mechanism has yet to be determined. The bioactive lipid mediators received attentions toward their contribution in cancer cell proliferation, progression and death. Amongst, 15-Lipoxygense (15-Lox) enzymes and products display appealing role in cancer pathogenesis which their possible effect in pituitary adenoma tumor genesis is perused in the current study. Methods The 15-Lipoxygenses isoforms expression level was evaluated in tumor tissues of prevalent functional and non-functional pituitary adenomas and normal pituitary tissues via Real-Time PCR. The circulating levels of 15(S) HETE and 13(S) HODE as 15-Lox main products were assessed in serum of patients and healthy subjects using enzyme immunoassay kits. Results Our results revealed that 15-Lox-1 and 15-Lox-2 expression levels were elevated in tumor tissues of pituitary adenomas comparing to normal pituitary tissues. The elevated levels of both isoforms were accompanied with 15(S) HETE and 13(S) HODE elevation in the serum of patients. The 15-Lox-1 expression and activity was higher in invasive tumors as well as tumors with bigger size indicating the possible pro-tumorigenic role of 15-Lox-1, more than 15-Lox-2 in pituitary adenomas. The diagnostic value of 15-Lipoxygense isoforms and products were considerable between patients and healthy groups. Conclusion The possible involvement of 15-Lipoxygense pathway especially 15-Lox-1 in the regulation of pituitary tumor growth and progression may open up new molecular mechanism regarding pituitary adenoma pathogenesis and might shed light on its new therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Up-regulation of 15-lipoxygenase enzymes and products in functional and non-functional pituitary adenomas

et al. 2019

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“…This gene codes for a 5-lipoxigenase activating protein and is thus involved in the synthesis of leukotrienes, implicated in a variety of inflammatory responses, including asthma, arthritis, and psoriasis. A recent study of the effect of inflammatory mediators belonging to the lipoxygenase family on the pathogenesis of MS showed higher levels of 15-lipoxygenase in patients with MS [ 47 ]. Furthermore, a study showed that GA may induce inflammation and immediate hypersensitivity through ALOX5AP [ 48 ].…”

Section: Pharmacogenetics Of Glatiramer Acetate In Msmentioning

confidence: 99%

Influence of Genetic Polymorphisms on Clinical Outcomes of Glatiramer Acetate in Multiple Sclerosis Patients

Zarzuelo

Pérez-Ramírez

Cura

et al. 2021

JPM

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Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of autoimmune origin, in which inflammation and demyelination lead to neurodegeneration and progressive disability. Treatment is aimed at slowing down the course of the disease and mitigating its symptoms. One of the first-line treatments used in patients with MS is glatiramer acetate (GA). However, in clinical practice, a response rate of between 30% and 55% is observed. This variability in the effectiveness of the medication may be influenced by genetic factors such as polymorphisms in the genes involved in the pathogenesis of MS. Therefore, this review assesses the impact of genetic variants on the response to GA therapy in patients diagnosed with MS. The results suggest that a relationship exists between the effectiveness of the treatment with GA and the presence of polymorphisms in the following genes: CD86, CLEC16A, CTSS, EOMES, MBP, FAS, TRBC1, IL1R1, IL12RB2, IL22RA2, PTPRT, PVT1, ALOX5AP, MAGI2, ZAK, RFPL3, UVRAG, SLC1A4, and HLA-DRB1*1501. Consequently, the identification of polymorphisms in these genes can be used in the future as a predictive marker of the response to GA treatment in patients diagnosed with MS. Nevertheless, there is a lack of evidence for this and more validation studies need to be conducted to apply this information to clinical practice.

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“…[3,4] It was considered that the occurrence and progression of MS may attribute to the virus infection, vitamin deficiency, mitochondrial dysfunction, and oxidative stress. [5] However, up to now, the exact reason for MS has not been determined.…”

Section: Introductionmentioning

confidence: 99%

Meta-analysis of FOXP3 gene rs3761548 and rs2232365 polymorphism and multiple sclerosis susceptibility

Zhang

Liu

et al. 2019

Medicine

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BackgroundMultiple sclerosis (MS) is a common autoimmune disease of the central nervous system (CNS), and is associated with genetic factors. FOXP3 gene polymorphism has been reported as the risk factor for MS, however, previous studies have showed conflicting results. The purpose of this study is to investigate the association between FOXP3 gene polymorphism and the susceptibility to MS.MethodsPubmed, Embase, library of Cochrane, and Web of Science were used to search the eligible articles from January 1980 up to October 2018. The odds ratio (ORs) and its 95% confidence intervals (CI) were used to evaluate the strength of association. Allele model, homozygote model, heterozygote model, dominant model, and recessive model were used to evaluate the association between FOXP3 gene polymorphism and MS.ResultsA total of 5 studies contained 1276 MS patients and 1447 controls (for rs3761548) and 600 MS patients and 640 controls (for rs2232365) were enrolled in this meta-analysis. The association showed significant differences in allele and dominant model for rs3761548 polymorphism. In addition, a clear tendency to significance was detected in homozygote and recessive model for rs3761548 (P = .052). Subgroup analysis indicated a significant risk of MS in all genotype models but heterozygotes in Asians.ConclusionFOXP3 gene polymorphism rs3761548 was associated with a higher MS risk, especially in Asians. This conclusion needs to be validated in more large samples and multiracial studies.Level of evidenceLevel III diagnostic study.

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The role of expression and activity of 15-Lipoxygenase isoforms and related cytokines in patients with Multiple Sclerosis and healthy controls

Cited by 11 publications

References 39 publications

Up-regulation of 15-lipoxygenase enzymes and products in functional and non-functional pituitary adenomas

Up-regulation of 15-lipoxygenase enzymes and products in functional and non-functional pituitary adenomas

Influence of Genetic Polymorphisms on Clinical Outcomes of Glatiramer Acetate in Multiple Sclerosis Patients

Meta-analysis of FOXP3 gene rs3761548 and rs2232365 polymorphism and multiple sclerosis susceptibility

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