MS14 Down-regulates Lipocalin2 Expression in Spinal Cord Tissue in an Animal Model of Multiple Sclerosis in female C57BL/6

Ebrahimi-Kalan, Abbas; Rad, Jafar Soleimani; Kafami, Laya; Mohammadnejad, Daryoush; Roudkenar, Mehryar Habibi; Khaki, Arash; Serej, Zeynab Aliyari; Roushandeh, Amaneh Mohammadi

doi:10.6091/ibj.1375.2014

Cited by 5 publications

(1 citation statement)

References 27 publications

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“…Not only is MS a disabling disease but it is also the leading cause of acquired neurological disability in young adults (Carvalho, 2013[ 9 ]; Ebrahimi-Kalan et al, 2014[ 13 ]). Even though focal inflammatory plaques and axonal loss are found to be the main pathological features of MS; however, the precise etiology of the disease is yet unknown (Loma and Heyman, 2011[ 29 ]; Koch et al, 2013[ 26 ]).…”

Section: Discussionmentioning

confidence: 99%

Toxic heavy metal concentrations in multiple sclerosis patients: a systematic review and meta-analysis

Sarihi

Niknam

Mahjour

et al. 2021

EXCLI Journal; 20:Doc1571; ISSN 1611-2156

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The present meta-analysis was performed to assess the association between MS patients and control subjects in terms of their circulating levels of arsenic (As), lead (Pb), mercury (Hg), and cadmium (Cd). We searched Medline/PubMed, Scopus, Web of Science, and Embase up until June 2020 to identify all studies that examined the concentrations of heavy metals in MS patients. Statistical tests used to assess inter-study heterogeneity were Cochrane's Q test and the I 2 statistic. Given the observed significant heterogeneity, the random-effects model was employed to pool the weighted mean differences (WMDs) and the corresponding 95 % confidence intervals (CIs). Out of a total of 1181 articles, 16 studies with 1650 participants (772 patients with MS and 878 controls) were included in this review meta-analysis. Pooled results using random-effects model showed that the levels of Pb (WMD= 0.73 µg/L, 95 % CI= 0.33 to 1.12, P< 0.001), As (WMD= 2.48 μg/L, 95 % CI= 1.44 to 3.53, P <0.001; I 2 = 98.9 %, P <0.001), and Cd (WMD= 0.17 μg/L, 95 % CI= 0.09 to 0.26, P <0.001) were significantly higher in MS patients than those of the controls. However, there were no significant differences in the levels of Hg (WMD= -0.14 µg/L, 95 % CI= -0.77 to 0.49, P= 0.658) among both groups. Sensitivity analysis indicated that after excluding one-by-one study, the overall pooled WMD of Pb was changed. This meta-analysis showed that patients with MS had significantly higher levels of circulatory As and Cd compared to the controls. Yet, there was no statistically significant difference between circulating levels of Hg and Pb among MS patients and controls. See also Figure 1 (Fig. 1) .

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Section: Discussionmentioning

confidence: 99%

Toxic heavy metal concentrations in multiple sclerosis patients: a systematic review and meta-analysis

Sarihi

Niknam

Mahjour

et al. 2021

EXCLI Journal; 20:Doc1571; ISSN 1611-2156

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Ectopic Expression of Innate Immune Protein, Lipocalin-2, in Lactococcus lactis Protects Against Gut and Environmental Stressors

Saha

Chassaing

Yeoh

et al. 2017

Inflammatory Bowel Diseases

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Background Lipocalin 2 (Lcn2) is a multifunctional innate immune protein that exhibits antimicrobial activity by the sequestration of bacterial siderophores, regulates iron homeostasis, and augments cellular tolerance to oxidative stress. Studies in the murine model of colitis have demonstrated that Lcn2 deficiency exacerbates colitogenesis, however, the therapeutic potential of Lcn2 supplementation has yet to be elucidated. In light of its potential mucoprotective functions, we herein investigated whether expression of Lcn2 in the probiotic bacterium can be exploited to alleviate experimental colitis. Methods Murine Lcn2 was cloned into the pT1NX plasmid and transformed into Lactococcus lactis to generate L. lactis expressing Lcn2 (LactisLcn2) or the empty plasmid (LactisCon). LactisLcn2 was characterized by immunoblot and ELISA, and tested for its antimicrobial efficacy on Escherichia coli. The capacity of LactisLcn2 and LactisCon to withstand adverse conditions were tested using in vitro viability assays. Dextran sodium sulfate colitis model was employed to investigate the colonization ability and therapeutic potential of LactisLcn2 and LactisCon. Results Lcn2-derived from LactisLcn2 inhibited the growth of E. coli and reduced the bioactivity of enterobactin (E. coli-derived siderophore) in vitro. LactisLcn2 displayed enhanced tolerance to adverse pH, high concentration of bile acids and oxidative stress in vitro, and survived better in the inflamed gut than LactisCon. Consistent with these features, LactisLcn2 displayed better mucoprotection against intestinal inflammation than LactisCon when administered into mice with DSS-induced acute colitis. Conclusions Our findings suggest that Lcn2 expression can be exploited to enhance the survivability of probiotic bacteria during inflammation, which could further improve its efficacy to treat experimental colitis.

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Marine-derived protein kinase inhibitors for neuroinflammatory diseases

et al. 2018

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Neuroinflammation is primarily characterized by overexpression of proinflammatory mediators produced by glial activation or immune cell infiltration. Several kinases have been shown to be critical mediators in neuroinflammation. One of the largest groups of kinases is protein kinases, which have been the second most studied group of drug targets after G-protein-coupled receptors. Thus far, most of the approved kinase inhibitor drugs are adenosine triphosphate-competitive inhibitors with various off-target liabilities because of cross-reactivities; however, marine-derived compounds provide opportunities for discovering allosteric kinase inhibitors. This review summarizes the potential of marine-derived protein kinase inhibitors in the field of neuroinflammatory diseases, such as Parkinson disease, Alzheimer disease, multiple sclerosis, and pain. The previous studies from 1990 to 2017 in this review have shown that marine-derived protein kinase inhibitors have great potential to elicit anti-neuroinflammatory or neuroprotective responses in in vitro and in vivo models of neuroinflammatory diseases. This suggests that further exploration and investigation of these marine-derived protein kinase inhibitors on neuroinflammatory diseases are warranted. Therefore, this review may inspire further discovery of new protein kinase inhibitors from a marine origin and additional neuroscience studies focusing on these valuable marine-derived protein kinase inhibitors.

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MS14 Down-regulates Lipocalin2 Expression in Spinal Cord Tissue in an Animal Model of Multiple Sclerosis in female C57BL/6

Cited by 5 publications

References 27 publications

Toxic heavy metal concentrations in multiple sclerosis patients: a systematic review and meta-analysis

Toxic heavy metal concentrations in multiple sclerosis patients: a systematic review and meta-analysis

Ectopic Expression of Innate Immune Protein, Lipocalin-2, in Lactococcus lactis Protects Against Gut and Environmental Stressors

Marine-derived protein kinase inhibitors for neuroinflammatory diseases

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