Specific in vitro binding of a new 99mTc-radiolabeled derivative of the C-terminal decapeptide of prothymosin alpha on human neutrophils

Karachaliou, Chrysoula-Evangelia; Liolios, Christos; Triantis, Charalampos; Zikos, Christos; Samara, Pinelopi; Tsitsilonis, Ourania E.; Kalbacher, Hubert; Voelter, Wolfgang; Papadopoulos, Minas; Pirmettis, Ioannis; Livaniou, Evangelia

doi:10.1016/j.ijpharm.2015.03.031

Cited by 11 publications

(13 citation statements)

References 51 publications

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“…Intracellularly, PTMA is associated with cell proliferation, apoptosis, and chromatin remodeling [Eschenfeldt and Berger, 1986;Gomez-Marquez and Rodriguez, 1998;Jiang et al, 2003]; extracellularly, PTMA and its fragment can stimulate the immune response, treat malignances, and promote angiogenesis [Pineiro et al, 2000;Koutrafouri et al, 2001]. Different regions of PTMA sequence have different biological functions: the region of 2-29aa produces active thymus hormone; the region of 42-101aa is Asp/Glu-rich region that maintain the acidic property, and the 49-82aa fragment is Zinc-binding region [Yi et al, 2007]; the Cterminal fragment (100-109aa), via targeting Toll-like receptor-4 (TLR 4), can be recognized and bound with neutrophils [Skopeliti et al, 2006;Karachaliou et al, 2015]. In addition, Caspase-3 cleaves human-PTMA at one C-terminal DDVD 99 to disrupt the nuclear localization signal of prothymosin, which is a profound alteration in subcellular localization of the truncated protein [Evstafieva et al, 2003].…”

Section: Discussionmentioning

confidence: 99%

Peptidomics Analysis of Transient Regeneration in the Neonatal Mouse Heart

Fan

Zhang

et al. 2017

J. Cell. Biochem.

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Neonatal mouse hearts have completely regenerative capability after birth, but the ability to regenerate rapidly lost after 7 days, the mechanism has not been clarified. Previous studies have shown that mRNA profile of adult mouse changed greatly compared to neonatal mouse. So far, there is no research of peptidomics related to heart regeneration. In order to explore the changes of proteins, enzymes, and peptides related to the transient regeneration, we used comparative petidomics technique to compare the endogenous peptides in the mouse heart of postnatal 1 and 7 days. In final, we identified 236 differentially expressed peptides, 169 of which were upregulated and 67 were downregulated in the postnatal 1 day heart, and also predicted 36 functional peptides associated with transient regeneration. The predicted 36 candidate peptides are located in the important domains of precursor proteins and/or contain the post-transcriptional modification (PTM) sites, which are involved in the biological processes of cardiac development, cardiac muscle disease, cell proliferation, necrosis, and apoptosis. In conclusion, for the first time, we compared the peptidomics profiles of neonatal heart between postnatal 1 day and postnatal 7 day. This study provides a new direction and an important basis for the mechanism research of transient regeneration in neonatal heart. J. Cell. Biochem. 118: 2828-2840, 2017. © 2017 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Peptidomics Analysis of Transient Regeneration in the Neonatal Mouse Heart

Fan

Zhang

et al. 2017

J. Cell. Biochem.

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“…Using as control a scrambled decapeptide with the same amino acid composition but a different primary structure, the immunoenhancing activity of proTα(100-109) was shown to be sequence-specific and comparable to that of intact proTα. Most recently, we reported that proTα(100-109) radiolabeled with (99m)Tc binds on the surface of human neutrophils via a complex involving TLR4 (Karachaliou et al, 2015) and selectively accumulates in sites of experimentally induced inflammation (C.E. Karachaliou et al, personal communication).…”

Section: The Carboxy-terminal Protα Peptides Exhibit Improved Immune mentioning

confidence: 99%

Prothymosin Alpha and Immune Responses

Samara

Ioannou

Tsitsilonis

2016

Vitamins and Hormones

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The thymus gland produces soluble molecules, which mediate significant immune functions. The first biologically active thymic extract was thymosin fraction V, the fractionation of which led to the isolation of a series of immunoactive polypeptides, including prothymosin alpha (proTα). ProTα displays a dual role, intracellularly as a survival and proliferation mediator and extracellularly as a biological response modifier. Accordingly, inside the cell, proTα is implicated in crucial intracellular circuits and may serve as a surrogate tumor biomarker, but when found outside the cell, it could be used as a therapeutic agent for treating immune system deficiencies. In fact, proTα possesses pleiotropic adjuvant activity and a series of immunomodulatory effects (eg, anticancer, antiviral, neuroprotective, cardioprotective). Moreover, several reports suggest that the variable activity of proTα might be exerted through different parts of the molecule. We first reported that the main immunoactive region of proTα is the carboxy-terminal decapeptide proTα(100-109). In conjunction with data from others, we also revealed that proTα and proTα(100-109) signal through Toll-like receptor 4. Although their precise molecular mechanism of action is yet not fully elucidated, proTα and proTα(100-109) are viewed as candidate adjuvants for cancer immunotherapy. Here, we present a historical overview on the discovery and isolation of thymosins with emphasis on proTα and data on some immune-related new activities of the polypeptide and smaller immunostimulatory peptides thereof. Finally, we propose a compiled scenario on proTα's mode of action, which could eventually contribute to its clinical application.

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“…However, oral solid formulations are gaining support from regulatory authorities, based on their better stability profile, lower number of (potentially hazardous) excipients and suitability for taste-masking and controlled-release via film coating 1 , 3 . This paradigm shift in the selection of the most appropriate dosage form has been reinforced by recent studies supporting acceptability of solid medicines in children, including the youngest populations of preschool children and neonates 4 – 9 .…”

Section: Introductionmentioning

confidence: 99%

Acceptability of placebo multiparticulate formulations in children and adults

Lopez

Mistry

Batchelor

et al. 2018

Sci Rep

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Patient acceptability is an important consideration in the design of medicines for children. The aim of this study was to investigate acceptability of multiparticulates in healthy children and adults. A randomised, single-blind acceptability testing was performed involving 71 children (4–12 years) and 61 adults (18–37 years). Each participant received three 500 mg samples of microcrystalline cellulose pellets administered on a medicine spoon with water at 5–10 minutes intervals. Acceptability was measured based on voluntary intake of the samples, facial expressions, ratings on hedonic scales and reported willingness to take multiparticulates everyday as a medicine. Multiparticulates were voluntarily swallowed by 92% of children and 100% of adults. However, palatability issues were identified, with emphasis on textural aspects. Grittiness perception received negative ratings on hedonic scales by 60% of children and 51% of adults. Researcher observations revealed that 72% of children and 42% of adults displayed negative facial expressions towards the samples. Children reported their willingness to take multiparticulates as a medicine in 30% of the cases, compared to 74% in adults. This study demonstrates that multiparticulates may be a suitable formulation platform for children and adults, although palatability concerns have been highlighted. Additional work is required to define acceptability criteria and to standardise methodologies.

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Specific in vitro binding of a new 99mTc-radiolabeled derivative of the C-terminal decapeptide of prothymosin alpha on human neutrophils

Cited by 11 publications

References 51 publications

Peptidomics Analysis of Transient Regeneration in the Neonatal Mouse Heart

Peptidomics Analysis of Transient Regeneration in the Neonatal Mouse Heart

Prothymosin Alpha and Immune Responses

Acceptability of placebo multiparticulate formulations in children and adults

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