Thymosin alpha 1: A comprehensive review of the literature

Dominari, Asimina; Hathaway, Donald; Pandav, Krunal; Matos, Wanessa; Biswas, Sharmi; Reddy, G. Narasimha; Thevuthasan, Sindhu; Khan, Muhammad Adnan; Mathew, Anoopa; Makkar, Sarabjot Singh; Zaidi, Madiha; Fahem, Michael Maher Mourad; Beas, Renato; Castaneda, Valeria; Paul, Trissa; Halpern, John H.; Baralt, Diana

doi:10.5501/wjv.v9.i5.67

Cited by 35 publications

(27 citation statements)

References 39 publications

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“…Thymalfasin is a synthetic analog of thymosin alpha 1 and is used for the treatment of chronic hepatitis B and C and as an immune enhancer for treating several other diseases [ 64 ]. Thymosin alpha 1 has a wide range of biological activities, which may explain its classification as a peptide hormone [ 64 ]. Further, MultiPep predictions indicate that the Thymalfasin may have minor neuropeptide properties.…”

Section: Resultsmentioning

confidence: 99%

MultiPep: a hierarchical deep learning approach for multi-label classification of peptide bioactivities

2021

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Peptide-based therapeutics are here to stay and will prosper in the future. A key step in identifying novel peptide-drugs is the determination of their bioactivities. Recent advances in peptidomics screening approaches hold promise as a strategy for identifying novel drug targets. However, these screenings typically generate an immense number of peptides and tools for ranking these peptides prior to planning functional studies are warranted. Whereas a couple of tools in the literature predict multiple classes, these are constructed using multiple binary classifiers. We here aimed to use an innovative deep learning approach to generate an improved peptide bioactivity classifier with capacity of distinguishing between multiple classes. We present MultiPep: a deep learning multi-label classifier that assigns peptides to zero or more of 20 bioactivity classes. We train and test MultiPep on data from several publically available databases. The same data are used for a hierarchical clustering, whose dendrogram shapes the architecture of MultiPep. We test a new loss function that combines a customized version of Matthews correlation coefficient with binary cross entropy (BCE), and show that this is better than using class-weighted BCE as loss function. Further, we show that MultiPep surpasses state-of-the-art peptide bioactivity classifiers and that it predicts known and novel bioactivities of FDA-approved therapeutic peptides. In conclusion, we present innovative machine learning techniques used to produce a peptide prediction tool to aid peptide-based therapy development and hypothesis generation.

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Section: Resultsmentioning

confidence: 99%

MultiPep: a hierarchical deep learning approach for multi-label classification of peptide bioactivities

2021

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“…C10, a phenyl derivative of MMI ( 17 ), is a more potent anti-inflammatory agent both in vitro and in vivo ( 17 , 45 ). Thymosin-α1 is a drug used to stimulate the immune response ( 46 ) and one of its mechanisms of action is the increase of MHC class I expression ( 20 , 47 ). The increased expression of MHC class I molecules on thyroid cells induced by the high glucose levels can be involved in the higher incidence of thyroid autoimmunity associated with hyperglycemia ( 48 , 49 ).…”

Section: Discussionmentioning

confidence: 99%

Hormonal Regulation of the MHC Class I Gene in Thyroid Cells: Role of the Promoter “Tissue-Specific” Region

et al. 2021

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In previous studies we have demonstrated that the expression of the Major Histocompatibility Complex (MHC) class I gene in thyrocytes is controlled by several hormones, growth factors, and drugs. These substances mainly act on two regions of the MHC class I promoter a “tissue-specific” region (−800 to −676 bp) and a “hormone/cytokines-sensitive” region (−500 to −68 bp). In a previous study, we have shown that the role of the “tissue-specific” region in the MHC class I gene expression is dominant compared to that of the “hormone/cytokines-sensitive” region. In the present report we further investigate the dominant role of the “tissue-specific” region evaluating the effect of thyroid stimulating hormone (TSH), methimazole (MMI), phenylmethimazole (C10), glucose and thymosin-α1. By performing experiments of electrophoretic mobility shift assays (EMSAs) we show that TSH, MMI and C10, which inhibit MHC class I expression, act on the “tissue-specific” region increasing the formation of a silencer complex. Glucose and thymosin-α1, which stimulate MHC class I expression, act decreasing the formation of this complex. We further show that the silencer complex is formed by two distinct members of the transcription factors families activator protein-1 (AP-1) and nuclear factor-kB (NF-kB), c-jun and p65, respectively. These observations are important in order to understand the regulation of MHC class I gene expression in thyroid cells and its involvement in the development of thyroid autoimmunity.

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“…Being a naturally occurring thymic peptide, it acts as an endogenous regulator of both innate and adaptive immune responses. It has a wide range of biological activities, including antitumor to immune-modulating activities [50]. Two meta-analyses of 12 and 10 RCTs identified significantly lower mortality in critically ill septic patients treated with Tα1-based immunotherapy [51,52].…”

Section: Thymosin Alpha-1mentioning

confidence: 99%

“…[56]. In addition to COVID-19, Tα1 has shown potential benefits in treating viral infections such as hepatitis C, hepatitis B, and human immunodeficiency virus, and has also been used as an influenza vaccine adjuvant [50].…”

Section: Thymosin Alpha-1mentioning

confidence: 99%

Therapeutic Approaches in Modulating the Inflammatory and Immunological Response in Patients With Sepsis, Acute Respiratory Distress Syndrome, and Pancreatitis: An Expert Opinion Review

Mehta¹,

Dixit²,

Zirpe³

et al. 2021

Cureus

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Immunomodulation has long been an adjunct approach in treating critically ill patients with sepsis, acute respiratory distress syndrome (ARDS), and acute pancreatitis (AP). Hyperactive immune response with immunopathogenesis leads to organ dysfunction and alters the clinical outcomes in critically ill. Though the immune response in the critically ill might have been overlooked, it has gathered greater attention during this novel coronavirus disease 2019 (COVID-19) pandemic. Modulating hyperactive immune response, the cytokine storm, especially with steroids, has shown to improve the outcomes in COVID-19 patients. In this review, we find that immune response pathogenesis in critically ill patients with sepsis, ARDS, and AP is nearly similar. The use of immunomodulators such as steroids, broad-spectrum serine protease inhibitors such as ulinastatin, thymosin alpha, intravenous immunoglobulins, and therapies such as CytoSorb and therapeutic plasma exchange may help in improving the clinical outcomes in these conditions. As the experience of the majority of physicians in using such therapeutics may be limited, we provide our expert comments regarding immunomodulation to optimize outcomes in patients with sepsis/septic shock, ARDS, and AP.

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Thymosin alpha 1: A comprehensive review of the literature

Cited by 35 publications

References 39 publications

MultiPep: a hierarchical deep learning approach for multi-label classification of peptide bioactivities

MultiPep: a hierarchical deep learning approach for multi-label classification of peptide bioactivities

Hormonal Regulation of the MHC Class I Gene in Thyroid Cells: Role of the Promoter “Tissue-Specific” Region

Therapeutic Approaches in Modulating the Inflammatory and Immunological Response in Patients With Sepsis, Acute Respiratory Distress Syndrome, and Pancreatitis: An Expert Opinion Review

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