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Seung Yun Lee, Mee Ja Park, Hye Kyung Lee, Hyun Jin Son, Chang Nam Kim, Joo Heon Kim, Dong Wook Kang
Background: Thymosin β4 is a multi-functional hormone-like polypeptide, being involved in cell migration, angiogenesis, and tumor metastasis. This study was undertaken to clarify the clinico-pathologic implications of thymosin β4 expression in human colorectal carcinomas (CRCs). Materials and Methods: We investigated tissue sections from 143 patients with CRC by immunohistochemistry. In addition, we evaluated the expression patterns and the clinico-pathological significance of thymosin β4 expression in association with hypoxia inducible factor-1α (HIF-1α) expression in the CRC series...
October 16, 2016: Journal of Pathology and Translational Medicine
Silvia Bosello, Giusy Peluso, Federica Iavarone, Barbara Tolusso, Irene Messana, Gavino Faa, Massimo Castagnola, Gianfranco Ferraccioli
BACKGROUND: In the present study, we investigated whether thymosin β (Tβ) in saliva and in minor salivary glands is differentially expressed in patients with primary Sjögren's syndrome (pSS) and patients with autoimmune diseases (systemic sclerosis [SSc], systemic lupus erythematosus [SLE], and rheumatoid arthritis [RA], with and without sicca syndrome [ss]). METHODS: Saliva specimens of nine patients with pSS, seven with ss/SSc, seven with ss/SLE, seven with ss/RA, seven with SSc, seven with SLE, and seven with RA, as well as ten healthy subjects, were analyzed using a high-performance liquid chromatograph coupled with a mass spectrometer equipped with an electrospray ionization source to investigate the presence and levels of Tβ4, Tβ4 sulfoxide, and Tβ10...
October 6, 2016: Arthritis Research & Therapy
E M Weissinger, C Human, J Metzger, L Hambach, D Wolf, H T Greinix, A M Dickinson, W Mullen, D Jonigk, Z Kuzmina, H Kreipe, P Schweier, O Böhm, I Türüchanow, D Ihlenburg-Schwarz, J Raad, A Durban, M Schiemann, C Könecke, H Diedrich, E Holler, G Beutel, J Krauter, A Ganser, M Stadler
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be curative, but is associated with significant morbidity and mortality. Chronic graft-versus-host disease (cGvHD), characterized by inflammation and fibrosis of multiple target organs, considerably contributes to the morbidity and mortality even years after allo-HSCT. Diagnosis of cGvHD is based on clinical features and histology of biopsies. Here, we report the generation of a urinary cGvHD-specific proteome-pattern (cGvHD_MS14) established by capillary electrophoresis-mass spectrometry to predict onset and severity of cGvHD as an unbiased laboratory test...
September 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
E V Navolotskaya, D V Zinchenko, Y A Zolotarev, A A Kolobov, V M Lipkin
The synthetic peptide LKEKK corresponding to sequence 16-20 of human thymosin-α1 and 131-135 of human interferon-α2 was labeled with tritium to specific activity 28 Ci/mol. The [3H]LKEKK bound with high affinity (Kd = 3.7 ± 0.3 nM) to donor blood T-lymphocytes. Treatment of cells with trypsin or proteinase K did not abolish [3H]LKEKK binding, suggesting the non-protein nature of the peptide receptor. The binding was inhibited by thymosin-α1, interferon-α2, and cholera toxin B subunit (Ki = 2.0 ± 0.3, 2...
August 2016: Biochemistry. Biokhimii︠a︡
Sing Wan Wong, Yifei Yao, Ye Hong, Zhiyao Ma, Stanton H L Kok, Shan Sun, Michael Cho, Kenneth K H Lee, Arthur F T Mak
High oxidative stress can occur during ischemic reperfusion and chronic inflammation. It has been hypothesized that such oxidative challenges could contribute to clinical risks such as deep tissue pressure ulcers. Skeletal muscles can be challenged by inflammation-induced or reperfusion-induced oxidative stress. Oxidative stress reportedly can lower the compressive damage threshold of skeletal muscles cells, causing actin filament depolymerization, and reduce membrane sealing ability. Skeletal muscles thus become easier to be damaged by mechanical loading under prolonged oxidative exposure...
September 20, 2016: Annals of Biomedical Engineering
Fang Liu, Hong-Mei Wang, Tiansheng Wang, Ya-Mei Zhang, Xi Zhu
BACKGROUND: Thymosin α1 (Tα1) as immunomodulatory treatment is supposed to be beneficial for the sepsis patients by regulating T cell subsets and inflammatory mediators. However, limited by the small sample size and the poor study design, the persuasive power of the single clinical studies is weak. This meta-analysis aimed to investigate the impact of Tα1 on the sepsis patients. METHODS: We searched for the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CBM, VIP, CNKI, WANFANG, Igaku Chuo Zasshi (ICHUSHI) and Korean literature databases reporting the effects of Tα1 on outcomes in sepsis patients...
2016: BMC Infectious Diseases
Z Y Wang, W Zhang, J J Yang, D K Song, J X Wei, S Gao
The clinical significance of thymosin β4 (Tβ4) expression in bladder transitional cell carcinoma (BTCC) remains unclear. The present study assessed the relationship between the expression of Tβ4 protein and the clinicopathological features, as well as the prognosis of bladder cancer patients. Tβ4 protein expression in 24 normal bladder and 138 primary BTCC tissue specimens was detected by immunohistochemistry, and the association of this expression with BTCC clinicopathological features and recurrence as well as patient survival was analyzed...
September 6, 2016: Neoplasma
Elisavet Vasilopoulou, Maria Kolatsi-Joannou, Maja T Lindenmeyer, Kathryn E White, Michael G Robson, Clemens D Cohen, Neil J Sebire, Paul R Riley, Paul J Winyard, David A Long
Glomerular disease is characterized by morphologic changes in podocyte cells accompanied by inflammation and fibrosis. Thymosin β4 regulates cell morphology, inflammation, and fibrosis in several organs and administration of exogenous thymosin β4 improves animal models of unilateral ureteral obstruction and diabetic nephropathy. However, the role of endogenous thymosin β4 in the kidney is unknown. We demonstrate that thymosin β4 is expressed prominently in podocytes of developing and adult mouse glomeruli...
November 2016: Kidney International
Dayu Huang, Shaohua Wang, An Wang, Xiaofeng Chen, Huijun Zhang
Thymosin beta 4 (Tβ4), a pleiotropic actin-sequestering polypeptide that is involved in wound healing and developmental processes, has been reported to be strongly associated with tumorigenesis. A recent tissue microarray analysis showed that Tβ4 was highly expressed in certain tumor cells, including lung cancer. However, the exact expression pattern and the role of Tβ4 in non-small cell lung cancer (NSCLC) have not to our knowledge been investigated. In the present study, we confirmed that Tβ4 expression was increased in NSCLC tissues and cell lines...
September 2016: Acta Biochimica et Biophysica Sinica
Rylosona Janarthini, Xiaolei Wang, Lulu Chen, Lei Gao, Lingxia Zhao
Thymosin β4 (Tβ4) is a peptide that is known to play important roles in protection, regeneration, and remodeling of injured tissues in humans, and that shows great promise in a range of clinical applications. However, current strategies to Tβ4 are insufficient to meet growing demand and have a number of limitations. In this current study we investigated whether expression of recombinant Tβ4 in plants, specifically in tobacco (Nicotiana tabacum) leaves, represents an effective approach. To address this question, a 168 bp Tβ4 gene optimized for tobacco codon usage bias was constitutively expressed in tobacco as a 4-unit repeat concatemer, fused to a polyhistidine tag...
2016: BioMed Research International
Giuseppina Maccarrone, Sandra Nischwitz, Sören-Oliver Deininger, Joachim Hornung, Fatima Barbara König, Christine Stadelmann, Christoph W Turck, Frank Weber
Multiple sclerosis is a disease of the central nervous system characterized by recurrent inflammatory demyelinating lesions in the early disease stage. Lesion formation and mechanisms leading to lesion remyelination are not fully understood. Matrix Assisted Laser Desorption Ionisation Mass Spectrometry imaging (MALDI-IMS) is a technology which analyses proteins and peptides in tissue, preserves their spatial localization, and generates molecular maps within the tissue section. In a pilot study we employed MALDI imaging mass spectrometry to profile and identify peptides and proteins expressed in normal-appearing white matter, grey matter and multiple sclerosis brain lesions with different extents of remyelination...
July 1, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
G Sosne, D Rimmer, H K Kleinman, G Ousler
Chronic ocular surface diseases such as dry eye, blepharitis, and neurotrophic keratopathies represent a significant and a growing therapeutic challenge. The basis of this expanding prevalence is multifactorial and may due to issues such as an aging population, an increasing use of video display terminals, and increases in frequency of refractive surgeries. The growing incidence of diseases such as diabetes may also be a contributing factor. Current treatments for ocular surface disease include artificial tears, lubricants, tear duct plugs, steroids, antibiotics, cyclosporine, scleral lenses, and serum tears...
2016: Vitamins and Hormones
H K Kleinman, G Sosne
No agent has been identified that significantly accelerates the repair of chronic dermal wounds in humans. Thymosin beta 4 (Tβ4) is a small, abundant, naturally occurring regenerative protein that is found in body fluids and inside cells. It was found to have angiogenic and antiinflammatory activity and to be high in platelets that aggregate at the wound site. Thus we used Tβ4 initially in dermal healing. It has since been shown to have many activities important in tissue protection, repair, and regeneration...
2016: Vitamins and Hormones
E D Marks, A Kumar
The burden of cardiovascular disease is a growing worldwide issue that demands attention. While many clinical trials are ongoing to test therapies for treating the heart after myocardial infarction (MI) and heart failure, there are few options doctors able to currently give patients to repair the heart. This eventually leads to decreased ventricular contractility and increased systemic disease, including vascular disorders that could result in stroke. Small peptides such as thymosin β4 (Tβ4) are upregulated in the cardiovascular niche during fetal development and after injuries such as MI, providing increased neovasculogenesis and paracrine signals for endogenous stem cell recruitment to aid in wound repair...
2016: Vitamins and Hormones
G T Pipes, J Yang
Treatment with thymosin beta 4 (Tβ4) reduces infarct volume and preserves cardiac function in preclinical models of cardiac ischemic injury. These effects stem in part from decreased infarct size, but additional benefits are likely due to specific antifibrotic and proangiogenic activities. Injected or transgenic Tβ4 increase blood vessel growth in large and small animal models, consistent with Tβ4 converting hibernating myocardium to an actively contractile state following ischemia. Tβ4 and its degradation products have antifibrotic effects in in vitro assays and in animal models of fibrosis not related to cardiac injury...
2016: Vitamins and Hormones
P Samara, K Ioannou, O E Tsitsilonis
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...
2016: Vitamins and Hormones
R King, C Tuthill
Thymosin alpha 1 (Ta1) is a peptide originally isolated from thymic tissue as the compound responsible for restoring immune function to thymectomized mice. Ta1 has a pleiotropic mechanism of action, affecting multiple immune cell subsets that are involved in immune suppression. Ta1 acts through Toll-like receptors in both myeloid and plasmacytoid dendritic cells, leading to activation and stimulation of signaling pathways and initiation of production of immune-related cytokines. Due to the immune stimulating effects of Ta1, the compound would be expected to show utility for treatment of immune suppression, whether related to aging or to diseases such as infection or cancer...
2016: Vitamins and Hormones
J Kim, Y Jung
Liver fibrosis, a major characteristic of chronic liver disease, is inappropriate tissue remodeling caused by prolonged parenchymal cell injury and inflammation. During liver injury, hepatic stellate cells (HSCs) undergo transdifferentiation from quiescent HSCs into activated HSCs, which promote the deposition of extracellular matrix proteins, leading to liver fibrosis. Thymosin beta 4 (Tβ4), a major actin-sequestering protein, is the most abundant member of the highly conserved β-thymosin family and controls cell morphogenesis and motility by regulating the dynamics of the actin cytoskeleton...
2016: Vitamins and Hormones
M Freire, C S Sarandeses, G Covelo, C Díaz-Jullien
Prothymosin α (ProTα), the precursor of the thymosin α1 and thymosin α11, is a 109-111 amino acids protein widely distributed in the mammalian tissues that is essential for the cell proliferation and survival through its implication on chromatin remodeling and in the proapoptotic activity. ProTα is phosphorylated at Thr residues by the M2 isoenzyme of the pyruvate kinase in a process that is dependent on the cell proliferation activity, which constitutes a novel dual functionality of this enzyme. The Thr residues phosphorylated are apparently dependent on the carcinogenic transformation of the cells...
2016: Vitamins and Hormones
B Xue, R C Robinson
Thymosin β4 (Tβ4) is a 43-amino acid signature motif peptide that defines the beta-thymosin (βT) family of proteins. βTs are intrinsically unstructured in their free states and undergo disorder-to-order transitions in carrying out their biological functions. This property poses challenges in determining their 3D structures, mainly favoring structural studies on the complexes formed between βTs and their interaction partners. One of the βTs' primary binding partners is monomeric actin, a major component of the cytoskeleton in eukaryotic cells...
2016: Vitamins and Hormones
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