Ulinastatin attenuates experimental autoimmune encephalomyelitis by enhancing anti-inflammatory responses

Ming, Feng; Shu, Yaqing; Yang, Yu; Zheng, Xueping; Li, Rui; Wang, Yuge; Dai, Yongqiang; Qiu, Wei; Lu, Zhengqi

doi:10.1016/j.neuint.2013.11.007

Cited by 29 publications

(22 citation statements)

References 55 publications

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“…This is certainly true of paroxonase 1 (PON1), a lipoprotein-binding enzyme responsible for reducing oxidative stress levels in the circulation [65,66]. AMBP, another significantly down-regulated vascular panel marker, serves as a precursor for the lipid transporter, bikunin, which has also been implicated in inflammation suppression and neuroprotection [80,81].…”

Section: Discussionmentioning

confidence: 99%

Integrated Proteomics Reveals Brain-Based Cerebrospinal Fluid Biomarkers in Asymptomatic and Symptomatic Alzheimer’s Disease

Higginbotham

Ping

Dammer

et al. 2019

Preprint

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Our results used an integrative proteomic approach to identify panels of CSF AD protein biomarkers with strong links to a variety of pathological mechanisms in the diseased brain.Abstract: Alzheimer's disease (AD) features a complex web of pathological processes beyond amyloid accumulation and tau-mediated neuronal death. To meaningfully advance AD therapeutics, there is an urgent need for novel biomarkers that comprehensively reflect these disease mechanisms. Here we applied an integrative proteomics approach to identify cerebrospinal fluid (CSF) biomarkers linked to a diverse set of pathophysiological processes in the diseased brain. Using multiplex proteomics, we identified >3,500 proteins across 40 CSF samples from control and AD patients and >12,000 proteins across 48 postmortem brain tissues from control, asymptomatic AD (AsymAD), AD, and other neurodegenerative cases. Co-expression network analysis of the brain tissues resolved 44 protein modules, nearly half of which significantly correlated with AD neuropathology. Fifteen modules robustly overlapped with proteins quantified in the CSF, including 271 CSF markers highly altered in AD. These 15 overlapping modules were collapsed into five panels of brain-linked fluid markers representing a variety of cortical functions. Neuron-enriched synaptic and metabolic panels demonstrated decreased levels in the AD brain but increased levels in diseased CSF. Conversely, glial-enriched myelination and immunity panels were highly increased in both the brain and CSF. Using high-throughput proteomic analysis, proteins from these panels were validated in an independent CSF cohort of control, AsymAD, and AD samples. Remarkably, several validated markers were significantly altered in AsymAD CSF and appeared to stratify subpopulations within this cohort. Overall, these brain-linked CSF biomarker panels represent a promising step toward a physiologically comprehensive tool that could meaningfully enhance the prognostic and therapeutic management of AD.

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Section: Discussionmentioning

confidence: 99%

Integrated Proteomics Reveals Brain-Based Cerebrospinal Fluid Biomarkers in Asymptomatic and Symptomatic Alzheimer’s Disease

Higginbotham

Ping

Dammer

et al. 2019

Preprint

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“…NFκB is essential for both innate and adaptive immunity (Feng et al, 2014). The factor is an inducible latent gene regulatory protein which is detected in most cell types and is involved in a range of inflammatory processes.…”

Section: Discussionmentioning

confidence: 99%

Involvement of AMPK, IKβα-NFκB and eNOS in the sildenafil anti-inflammatory mechanism in a demyelination model

et al. 2015

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“…MMP, particularly MMP-9, is an important factor involved in acute spinal cord injury (9). Feng et al reported that ulinastatin protects against experimental autoimmune encephalomyelitis through downregulation of the expression of MMP-9 (10), and Zhang et al indicated that nutrient mixture attenuated SCI-induced impairment by negatively affecting the promoter activity of MMP-2 and MMP-9 in mice (11).…”

Section: Introductionmentioning

confidence: 99%

Effect of rutin on spinal cord injury through inhibition of the expression of MIP-2 and activation of MMP-9, and downregulation of Akt phosphorylation

Zhang

2015

Molecular Medicine Reports

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Rutin has extensive pharmacological activities, including antibacterial and anti-inflammatory activities, cooling of the blood to inhibit bleeding, reducing capillary wall fragility and anti-influenza activities. However, whether rutin can ameliorate neuropathic function in spinal cord injury (SCI) in constriction-induced peripheral nerve injury remains to be elucidated. In the present study, the potential protective effects of rutin on SCI rats were investigated. Neurological function was examined using the Basso, Beattie and Bresnahan (BBB) scoring system and by measuring the water content of the spinal cord tissue in SCI rats. SCI-induced programmed cell death was measured using hematoxylin and eosin staining. In addition, the expression of macrophage inflammatory protein-2 (MIP-2) and the activation of matrix metalloproteinase-9 (MMP-9) in the SCI rats were evaluated using ELISA assay kits and zymographic analysis, respectively. The phosphorylation of protein kinase B (p-Akt) was analyzed using a western blot assay. The results demonstrated that administrating rutin began to increase BBB scores and attenuate the spinal cord water content of the SCI rats. Administrating rutin prevented SCI-induced programmed cell death. The SCI rats of in the rutin-treated group were found to exhibit lower expression levels of MIP-2 and p-Akt, reduced MMP-9 activation, compared with the SCI model rats. In conclusion, rutin was demonstrated as a potential protective agent in SCI and enhances the neurotrophic effect by inhibiting the expression of MIP-2 and activation of MMP-9, and downregulating the expression of p-Akt.

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Ulinastatin attenuates experimental autoimmune encephalomyelitis by enhancing anti-inflammatory responses

Cited by 29 publications

References 55 publications

Integrated Proteomics Reveals Brain-Based Cerebrospinal Fluid Biomarkers in Asymptomatic and Symptomatic Alzheimer’s Disease

Integrated Proteomics Reveals Brain-Based Cerebrospinal Fluid Biomarkers in Asymptomatic and Symptomatic Alzheimer’s Disease

Involvement of AMPK, IKβα-NFκB and eNOS in the sildenafil anti-inflammatory mechanism in a demyelination model

Effect of rutin on spinal cord injury through inhibition of the expression of MIP-2 and activation of MMP-9, and downregulation of Akt phosphorylation

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