mimetic peptide
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2022 ◽  
Author(s):  
Caryn E Plummer ◽  
Timothy Polk ◽  
Jatin Sharma ◽  
Sarah Bae ◽  
Olivia Barr ◽  
...  

Abstract Equine recurrent uveitis (ERU) is a painful and debilitating autoimmune disease, and represents the only spontaneous model of human recurrent uveitis (RU). Despite the efficacy of existing treatments, RU remains a leading cause of visual handicap in horses and humans. Cytokines, which utilize Janus kinase 2 (Jak2) for signaling, drive the inflammatory processes in ERU that promote blindness. Notably, suppressor of signaling-1 (SOCS1), which naturally limits the activation of Jak2 through binding interactions, is often deficient in autoimmune disease patients. Significantly, we previously showed that topical administration of a SOCS1 peptide mimic (SOCS1-KIR) mitigated induced rodent uveitis. In this pilot study, we test the potential to translate the therapeutic efficacy observed in experimental rodent uveitis to equine patient disease. Through bioinformatics and peptide binding assays we demonstrate putative binding of the SOCS1-KIR peptide to equine Jak2. We also show that topical, or intravitreal injection of SOCS1-KIR was well tolerated within the equine eye through physical and ophthalmic examinations. Finally, we show that topical SOCS1-KIR administration was associated with significant clinical ERU improvement. Together, these results provide a scientific rationale, and supporting experimental evidence for the therapeutic use of a SOCS1 mimetic peptide in RU.


2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Yongfa Zhang ◽  
Baocheng Gao ◽  
Jingsong Ouyang ◽  
Bai Tai ◽  
Shuai Zhou

Subarachnoid hemorrhage (SAH) is a kind of severe hemorrhagic stroke, and early brain injury acted as one of the main causes of death and delayed neurological deficit in patients with subarachnoid hemorrhage. In this process, the function and structural integrity of the blood-brain barrier play an important role. In this study, we have observed whether the apolipoprotein E (apoE) mimetic peptide, COG133, can alleviate early brain injury after subarachnoid hemorrhage. For this purpose, an experimental subarachnoid hemorrhage model was constructed in mice and treated by intravenous injection of COG133 at a dosage of 1 mg/kg. Then, the function and integrity of the blood-brain barrier were detected, and the pyroptosis level of the neuron was determined. The results showed that COG133 could protect blood-brain barrier function and structure integrity, reduce early brain injury, and ameliorate neurological function after subarachnoid hemorrhage. In terms of molecular mechanism, COG133 inhibits blood-brain barrier destruction through the proinflammatory CypA-NF-κB-MMP9 pathway and reduces neuronal pyroptosis by inhibiting NLRP3 inflammasome activation. In conclusion, this study demonstrated that apoE-mimetic peptide, COG133, can play a neuroprotective role by protecting blood-brain barrier function and inhibiting brain cell pyroptosis to reduce early brain injury after subarachnoid hemorrhage.


Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3170
Author(s):  
Ana Paula Girol ◽  
Caroline de Freitas Zanon ◽  
Ícaro Putinhon Caruso ◽  
Sara de Souza Costa ◽  
Helena Ribeiro Souza ◽  
...  

Uveitis is one of the main causes of blindness worldwide, and therapeutic alternatives are worthy of study. We investigated the effects of piperlongumine (PL) and/or annexin A1 (AnxA1) mimetic peptide Ac2-26 on endotoxin-induced uveitis (EIU). Rats were inoculated with lipopolysaccharide (LPS) and intraperitoneally treated with Ac2-26 (200 µg), PL (200 and 400 µg), or Ac2-26 + PL after 15 min. Then, 24 h after LPS inoculation, leukocytes in aqueous humor, mononuclear cells, AnxA1, formyl peptide receptor (fpr)1, fpr2, and cyclooxygenase (COX)-2 were evaluated in the ocular tissues, along with inflammatory mediators in the blood and macerated supernatant. Decreased leukocyte influx, levels of inflammatory mediators, and COX-2 expression confirmed the anti-inflammatory actions of the peptide and pointed to the protective effects of PL at higher dosage. However, when PL and Ac2-26 were administered in combination, the inflammatory potential was lost. AnxA1 expression was elevated among groups treated with PL or Ac2-26 + PL but reduced after treatment with Ac2-26. Fpr2 expression was increased only in untreated EIU and Ac2-26 groups. The interaction between Ac2-26 and PL negatively affected the anti-inflammatory action of Ac2-26 or PL. We emphasize that the anti-inflammatory effects of PL can be used as a therapeutic strategy to protect against uveitis.


2021 ◽  
Vol 116 ◽  
pp. 105379
Author(s):  
Lucia De Rosa ◽  
Donatella Diana ◽  
Rossella Di Stasi ◽  
Alessandra Romanelli ◽  
Michele F.M. Sciacca ◽  
...  
Keyword(s):  

Biomaterials ◽  
2021 ◽  
Vol 277 ◽  
pp. 121078
Author(s):  
Christopher M. Baehr ◽  
Lu Zhang ◽  
Yi Wu ◽  
Andras Domokos ◽  
Wenwu Xiao ◽  
...  

ACS Nano ◽  
2021 ◽  
Author(s):  
Michelle W. Lee ◽  
Elizabeth Wei-Chia Luo ◽  
Carlos Silvestre-Roig ◽  
Yashes Srinivasan ◽  
Kiyotaka Akabori ◽  
...  

2021 ◽  
Author(s):  
Sayani Chattopadhyay ◽  
Leandro B. C. Teixeira ◽  
Laura L. Kiessling ◽  
Jonathan F. McAnulty ◽  
Ronald T. Raines

ABSTRACTTransforming growth factor-β (TGF-β) plays important roles in wound healing. The activity of TGF-β is initiated upon binding of the growth factor to extracellular domains of its receptors. We sought to facilitate activation by clustering these extracellular domains. To do so, we used a known peptide that binds to TGF-β receptors without diminishing their affinity for TGF-β. We conjugated this peptide to a collagen-mimetic peptide that can anneal to damaged collagen in a wound bed. We find that the conjugate enhances collagen deposition and wound closure in mice in a manner consistent with the clustering of TGF-β receptors. This strategy provides a means to upregulate the TGF-β signaling pathway without adding exogenous TGF-β and could inspire means to treat severe wounds.TOC Graphic


2021 ◽  
Vol 174 ◽  
pp. 53-62
Author(s):  
Tárika Gonçalves do Carmo Oliveira ◽  
Ana Cláudia Moreira dos Santos ◽  
Alex Dias Assis ◽  
Raphael Teixeira Borges ◽  
Jéssica Regina da Costa Silva ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4888
Author(s):  
Jeremy Gleaton ◽  
Ryan W. Curtis ◽  
Jean Chmielewski

Here, the hierarchical assembly of a collagen mimetic peptide (CMP) displaying four bipyridine moieties is described. The CMP was capable of forming triple helices followed by self-assembly into disks and domes. Treatment of these disks and domes with metal ions such as Fe(II), Cu(II), Zn(II), Co(II), and Ru(III) triggered the formation of microcages, and micron-sized cup-like structures. Mechanistic studies suggest that the formation of the microcages proceeds from the disks and domes in a metal-dependent fashion. Fluorescently-labeled dextrans were encapsulated within the cages and displayed a time-dependent release using thermal conditions.


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