Thymopentin

Endogenous L-Carnosine Level in Diabetes Rat Cardiac Muscle.[Pubmed:27190533]

Evid Based Complement Alternat Med. 2016;2016:6230825.

A novel method for quantitation of cardiac muscle carnosine levels using HPLC-UV is described. In this simple and reliable method, carnosine from the rat cardiac muscle and the internal standard, Thymopentin, were extracted by protein precipitation with acetonitrile. The method was linear up to 60.96 mug.mL(-1) for L-carnosine. The calibration curve was linear in concentration ranges from 0.5 to 60.96 mug.mL(-1). The relative standard deviations obtained for intra- and interday precision were lower than 12% and the recoveries were higher than 90% for both carnosine and internal standard. We successfully applied this method to the analysis of endogenous carnosine in cardiac muscle of the diabetes rats and healthy control rats. The concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats. These results support the usefulness of this method as a means of quantitating carnosine and illustrate the important role of L-carnosine in cardiac muscle.

The Immunoendocrine Thymus as a Pacemaker of Lifespan.[Pubmed:27352969]

Acta Microbiol Immunol Hung. 2016 Jun;63(2):139-58.

The thymus develops from an endocrine area of the foregut, and retains the ancient potencies of this region. However, later it is populated by bone marrow originated lymphatic elements and forms a combined organ, which is a central part of the immune system as well as an influential element of the endocrine orchestra. Thymus produces self-hormones (thymulin, thymosin, Thymopentin, and thymus humoral factor), which are participating in the regulation of immune cell transformation and selection, and also synthesizes hormones similar to that of the other endocrine glands such as melatonin, neuropeptides, and insulin, which are transported by the immune cells to the sites of requests (packed transport). Thymic (epithelial and immune) cells also have receptors for hormones which regulate them. This combined organ, which is continuously changing from birth to senescence seems to be a pacemaker of life. This function is basically regulated by the selection of self-responsive thymocytes as their complete destruction helps the development (up to puberty) and their gradual release in case of weakened control (after puberty) causes the erosion of cells and intercellular material, named aging. This means that during aging, self-destructive and non-protective immune activities are manifested under the guidance of the involuting thymus, causing the continuous irritation of cells and organs. Possibly the pineal body is the main regulator of the pacemaker, the neonatal removal of which results in atrophy of thymus and wasting disease and its later corrosion causes the insufficiency of thymus. The co-involution of pineal and thymus could determine the aging and the time of death without external intervention; however, external factors can negatively influence both of them.

A Novel MS-Cleavable Azo Cross-Linker for Peptide Structure Analysis by Free Radical Initiated Peptide Sequencing (FRIPS).[Pubmed:28717933]

J Am Soc Mass Spectrom. 2017 Oct;28(10):2039-2053.

The chemical cross-linking/mass spectrometry (MS) approach is a growing research field in structural proteomics that allows gaining insights into protein conformations. It relies on creating distance constraints between cross-linked amino acid side chains that can further be used to derive protein structures. Currently, the most urgent task for designing novel cross-linking principles is an unambiguous and automated assignment of the created cross-linked products. Here, we introduce the homobifunctional, amine-reactive, and water soluble cross-linker azobisimidoester (ABI) as a prototype of a novel class of cross-linkers. The ABI-linker possesses an innovative modular scaffold combining the benefits of collisional activation lability with open shell chemistry. This MS-cleavable cross-linker can be efficiently operated via free radical initiated peptide sequencing (FRIPS) in positive ionization mode. Our proof-of-principle study challenges the gas phase behavior of the ABI-linker for the three amino acids, lysine, leucine, and isoleucine, as well as the model peptide Thymopentin. The isomeric amino acids leucine and isoleucine could be discriminated by their characteristic side chain fragments. Collisional activation experiments were conducted via positive electrospray ionization (ESI) on two Orbitrap mass spectrometers. The ABI-mediated formation of odd electron product ions in MS/MS and MS(3) experiments was evaluated and compared with a previously described azo-based cross-linker. All cross-linked products were amenable to automated analysis by the MeroX software, underlining the future potential of the ABI-linker for structural proteomics studies. Graphical Abstract .

Coupling Microchip Electrospray Ionization Devices with High Pressure Mass Spectrometry.[Pubmed:29151340]

Anal Chem. 2017 Dec 19;89(24):13320-13325.

A microchip electrospray ionization source was coupled with high pressure mass spectrometry (HPMS). A continuous atmospheric inlet consisting of a stainless steel capillary and DC ion optics was designed to conduct ions into the mass spectrometer. Infusions of amino acids and peptides were performed and detected with a miniature cylindrical ion trap (mini-CIT)-based mass spectrometer operated at >/=1 Torr with air as the buffer gas. Detection of glycine and Thymopentin (separately) demonstrated the mass range of the mini-CIT detector could span from m/z 75 to 681. A microchip capillary electrophoresis (CE) separation with mini-CIT detection was performed, and the results were compared with detection using a commercial instrument (Waters Synapt G2). Comparable separation efficiencies were observed with both mass spectrometers as detectors, with about 6 times better signal-to-noise observed on the Synapt G2. Comparison of mass spectra in the two systems reveals similar features observed, but with wider peak widths in the mini-CIT than on the Synapt G2 as expected due to high-pressure operation.

Myristic acid-modified thymopentin for enhanced plasma stability and immune-modulating activity.[Pubmed:28365509]

Int Immunopharmacol. 2017 Jun;47:88-94.

Natural albumin ligand (fatty acids)-conjugated peptides can rapidly bind to circulating albumin and form complexes to control the release of peptides. The purpose of this study was to prolong the half-life and immune-modulating effects of Thymopentin (TP5) by using the albumin binding strategy. We synthesized myristic acid-modified TP5 (TP5-MA) by conjugating a myristic acid-acylated lysine to a permissive site of TP5, which improved the albumin binding affinity of TP5-MA and dramatically enhanced its stability in human plasma. We observed well-preserved bioactivities of TP5-MA in RAW264.7 macrophages using a tumor necrosis factor (TNF)-alpha stimulation assay. Moreover, the prolonged immune-modulating effect of TP5-MA was confirmed by the normalized CD4(+)/CD8(+) ratio in immune-depressed rat models, which resulted in a reduced administration frequency (twice per week). In general, the enhanced pharmacokinetic and pharmacodynamic properties of TP5-MA make it a promising product for the treatment of immunodeficiency diseases.

A 6-year treatment experience for pemphigus: retrospective study of 69 Chinese patients.[Pubmed:27060935]

Dermatol Ther. 2016 Mar-Apr;29(2):84-7.

There is a lack of data on treatment and prognosis of pemphigus in China. The aim of this study was to evaluate long-term follow-up and prognosis of pemphigus. Forty-seven inpatients with pemphigus vulgaris (PV) and 22 with pemphigus foliaceus (PF) were recruited in this retrospective study. The average age at onset was 51.6 and 54.9 years in PV and PF, respectively. High-dose systemic steroids were administered in 47 PV and 21 PF, of which 18 PV and 8 PF with adjuvant therapies. CD4 lymphocytopenia was found in 5 PV and 2 PF patients at admission and successfully treated by intravenous Thymopentin daily. During a mean follow-up of 37.1 months, 41 PV and 19 PF reached remission, 30 PV and 9 PF relapsed, 4 PV and 2 PF died. Major causes of death were relapse of pemphigus due to discontinuation of oral steroids by the patients themselves (four cases) and severe infections (two cases, one with severe CD4 lymphocytopenia). The 1-year mortality rate of PV and PF was 8.5% and 4.5%, respectively. Cox regression analysis indicated that age at onset of pemphigus was an independent risk factor related to the elevated mortality. Our report confirmed the high mortality rate of pemphigus in a Chinese population and stressed that patient education was urgently needed to prevent relapses and deaths.

Thymopentin is a biologically active peptide secreted mainly by the epithelial cells of thymic cortex and medulla. Thymopentin is an effective immunomodulatory agent with a short plasma half-life of 30 seconds. Thymopentin enhances the generation of T-cell lineage derived from human embryonic stem cells (hESCs).

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