Thymalin: Activation of Differentiation of Human Hematopoietic Stem Cells.

Thymalin is a polypeptide complex isolated from the thymus and regulating the functions of the immune system. Thymalin is effective in therapy of acute respiratory syndrome, chronic obstructive bronchitis, and other immunopathology. Thymalin increases functional activity of T lymphocytes, but the targeted molecular mechanism of its biological activity requires further study. We studied the influence of thymalin on differentiation of human hematopoietic stem cells (HSC) and expression of CD28 molecule involved in the implementation of antiviral immunity in COVID-19 infection. It was found that thymalin reduced the expression of CD44 (stem cell marker) and CD117 (molecule of the intermediate stage of HSC differentiation) by 2-3 times and increased the expression of CD28 (marker of mature T lymphocytes) by 6.8 times. This indirectly indicates that thymalin stimulated differentiation of CD117+ cells into mature CD28+T lymphocytes. It is known that in patients with severe COVID-19, the number of CD28+, CD4+, CD8+T lymphocytes in the blood decreased, which attested to a pronounced suppression of immunity. It is possible that the antiviral effect of thymalin consists in compensatory stimulation of HSC differentiation into CD28+T lymphocytes at the stage of immunity suppression in unfavorable course of viral infection. Thymalin can be considered as an immunoprotective peptide drug for the prevention of COVID-19.

Chrono- and Immunocorrection of Inflammatory Disorders of Internal Reproductive Organs in Women of Reproductive Age.

We compared the effectiveness of immunomodulators used in the treatment of patients with chronic salpingitis and oophoritis with or without changes in succinate dehydrogenase (SDH) activity in blood lymphocytes at incubation with the drug. Diurnal variations in individual reaction of SDH in blood lymphocytes to thymalin or ridostin were revealed. In the groups of women receiving ridostin or thymalin during the reaction of lymphocyte SDH to it, improvement of clinical laboratory and immunological parameters was observed in the majority of the patients and no effect was found in a lesser group of patients than in the groups treated with drugs during the absence of lymphocyte SDH reaction thereto. The timing of the presence of SDH reaction to drugs in the immunocompetent cells makes it possible to set the optimal daily regime of their application and to select a drug that would be most effective in each particular case.

[Comparative study of immunomodulatory activity of peptides, tinrostim and thymalin].

The immunomodulatory activity of peptide drugs i.e. tinrostim (dosage form) prepared of squid optical ganglia and pharmacopoeia thymain was studied. Tinrostim showed a stimulating effect on the humoral and cellular nimmune responses when administered parenterally in experimental animals, as well as on the phagocytic activity of neutrophils, comparable to the effect of thymalin. It was demonstrated that both the peptide drugs increased the production of pro-(TNFa, IL-1) and antiinflammatory (IL- 10) cytokines in the culture of intact cells of peripheral blood in vitro. It is essential that when tinrostim was used in 10-fold different doses (0.005 mg / kg and 0.05 mg /kg) in mice, the effect of the lower dose was comparable to the effect of the higher dose.

[Thymus and adaptive changes of bone marrow cell composition in animals of different age].

The influence of thymus removal or administration of thymalin, thymic peptide factor, on number of cells-precursors for colonies of fibroblasts (CFC-F) and for granulocyte-macrophageal colonies (CFC-GM), CD(4+)-cells in bone marrow in CBA mice of different age in some seasons was investigated. It was shown that in adult mice the orientation of influence thymic activity modulation on amount of these types cells is dependent from seasons. It was shown the season possibility of direct effect of thymic stroma supernatant, in which was thymic serum factor (FTS), or the synthetic FTS on the amount of CFC-F and CFC-GM in bone marrow of adult mice; in old mice thymic supernatant increased in vitro the amount of CD(4+)-cells. FTS level in old mice increased after administration of thymalin, the rhythm of CD(4+)-cells number in bone marrow and of corticosterone serum content restored.

Protective effect of thymic humoral factor on porcine serum-induced hepatic fibrosis and liver damage in Wistar rats.

INTRODUCTION: Immunomodulatory drugs have been reported to have anti-inflammatory and anti-fibrotic properties. Thymic humoral factor (THF), a peptide produced in the thymus, causes a potent immunomodulatory effect on different components of the immune system. OBJECTIVE: To evaluate the effect of THF on different stages of liver damage and fibrosis induced in rats through the administration of porcine serum (PS). MATERIAL AND METHODS: PS-induced liver fibrosis models serve as a primarily immunological mechanism in the development of liver damage and fibrosis. RESULTS: The intraperitoneal administration of THF in rats with PS-induced liver damage produced a reduction of ALT and AST after 60 days. Histopathological changes in liver sections showed an improved histological appearance and lower % of fibrosis after 60 days in liver damaged rats that received THF treatment. Serum IL-6 levels were visibly reduced by THF administration after 60 days and in comparison with rats that did not receive the treatment. This was due to an increment in serum IL-10 levels caused by the administration of THF, which appears to reduce the inflammatory process by decreasing immune response. CONCLUSION: THF had beneficial effects in combating liver damage and fibrosis processes in an autoimmune model of PS-induced liver fibrosis in rats.

[Characteristics of the pineal gland and thymus relationship in aging].

The review presents the interference between thymus and pineal gland during their involution. The research data of thymus peptides influence on pineal gland and pineal peptides on thymus are summarized. Analysis of these data showed that pineal peptides (Epithalamin, Epitalon) had more effective geroprotective effect on thymus involution in comparison with geroprotective effect of thymic peptides (Thymalin, Thymogen) on involution of pineal gland. The key mechanisms of pineal peptides effect on thymus dystrophy is immunoendocrine cooperation, which is realized as transcription's activation of various proteins.

[Age- and sex-related differences of neuroendocrine center reactions in the hypothalamus on preparation thymalin and alpha-tocopherol acetate].

In experiment the action of Thymalin, alpha-tocopherol and stress on the centers of hypothalamus related to the regulation of the gonadotropic function has been investigated and the age-specific features of such influence as well. The results of experiments indicate the presence of neuron's reaction of the rostra preoptical area and arcuate nucleus for experimental influences. As a stress exposure and alpha-tocopherol injection to the young animals a reduction of neuron's kernels of the arcuate nucleus was observed, a sexual distinction wasn't revealed in the process. The response age-specific feature for alpha-tocopherol injection of the nucleus neuron's rostra preoptical and arcuate area of the hypothalamus of white rats is a reduction in a degree of response. Thymalin reduces a threshold of sensitivity of the neuron's arcuate center to action of stress.

Human thymic hormones increase in vitro IL-4 production in atopic patients.

BACKGROUND: There is little information about the relationship between thymic hormones and atopy. METHODS: Human thymostimulin was obtained from thymus of children who died in car crashes. These polypeptides were purified by a Sephadex G-50 column fractionation and incubated in vitro with human lymphocytes obtained from atopic and non-atopic subjects of different ages. The SDS-PAGE revealed at least the presence of three broad bands of proteins with 20, 30 and 60 kDa of molecular weight approximately. Levels of IL-4 from lymphocytic cultures were measured by ELISA and correlated with atopic and non-atopic status and with age. The non-atopic controls showed 5.20 UI/ml +/- 1.14 UI/ml of IL-4 meanwhile the non-atopic cells stimulated showed 8.15 UI/ml +/- 2.438 UI/ml. On the other hand, the atopic cells revealed a spontaneous release of 12 +/- 1.812 UI/ml meanwhile those stimulated by the thymostimulin showed 18.53 UI/ml +/- 1.40 UI/ml. RESULTS: Thymic polypeptides were able to increase the levels of IL-4 in both groups although the atopic subjects showed the greater increase (p > 0.001) independently of their age. CONCLUSIONS: As it has been suggested that these hormones could be used therapeutically in atopic subjects, our results warn about the adverse effects that could be produced with them.

[Thymic factors influence on melatonin-producing pineal function in mice of different age: the possible mechanisms].

The aging peculiarities of thymic factors influence on pineal gland function in CBA mice were investigated. Significant increase of melatonin serum level in 3 h and decrease in 24 h after one injection of thymic preparation "thymalin" in adult mice was shown. The activating influence of thymalin was depended on season and linked with increase of thymic serum factor (FTS, thymulin) level and decrease of corticosterone blood level. Thymic stroma supernatant of adult mice, which had high level of FTS, intensified in vitro melatonin-producing pineal function. The activating influence of thymic factors in vivo and in vitro on pineal function in old mice was not revealed. FTS content increased and cortocosterone level did not change in old mice after injection of thymalin. The mechanisms of thymic factors influence on melatonin level in adult organism and their peculiarities in aging were discussed.

Unfolding of higher DNA structures formed by the d(CGG) triplet repeat by UP1 protein.

Fragile X syndrome is caused by expansion of a d(CGG) triplet repeat in the 5'-untranslated region of the first exon of the FMR1 gene resulting in silencing of the gene. The d(CGG) repeat has been reported to form hairpin and quadruplex structures in vitro, and formation of these higher structures could be responsible for its unstable expansion in the syndrome, although molecular mechanisms underlying the repeat expansion still remain elusive. We have previously proved that UP1, a proteolytic product of hnRNP A1, unfolds the intramolecular quadruplex structures of d(GGCAG)5 and d(TTAGGG)4 and abrogates the arrest of DNA synthesis at d(GGG)n sites. Here, we demonstrate that the d(CGG) repeat forms a peculiar DNA structure, which deviates from the canonical B-form structure. In addition, UP1 was demonstrated by CD spectrum analysis to unfold this characteristic higher structure of the d(CGG) repeat and to abrogate the arrest of DNA synthesis at the site. This ability of UP1 suggests that unfolding of unusual DNA structures of a triplet repeat is required for DNA synthesis processes.

[Age-related characteristics of the thymus and adrenal cortex function in CBA mice immunized by T-dependent antigen].

The thymic serum factor (FTS) titer and corticosterone level in blood of adult and old CBA mice after immunization by T-dependent antigen was investigated. It has been revealed that in adult mice these indices influenced by phase changes in dynamics of immunization whereas in old mice fluctuations of FFS and corticosterone levels were monotonous. In both adult and old mice the correlation exists between thymic hormone and corticosterone. The increasing of thymic function by thymaline administration did not improve the dynamics of FTS titer and corticosterone level in immunized old mice.

[The functional condition of the immune system and the lymphocytes' hemopoiesis-modulating properties]. / Funktsional'noe sostoianie immunnoi sistemy i gemopoézmoduliruiushchie svoistva limfotsitov.

Donor splenocytes and timocytes have an ability to stimulate erythropoesis after massive blood-letting. Changing of functional state of the immune system by means of immune modulators action affects the character and expressiveness of hemopoiesis regulation function of lymphocytes. Splinocytes and thymocytes depress granulocytopoiesis in the recipients' bone marrow after activation by T- and B-lymphocytes. The activation of B-lymphocytes determines the cells' capacity to increase concentration of thrombocytes in the blood. Donor thymocytes can activate erythropoiesis and granulocytopoiesis after macrophages stimulation.

[Effect of thyroxin and thymalin on proliferation and apoptosis of thymocytes in rats after thyroidectomy]. / Vplyv tyroksynu i tymalinu na proliferatsiiu ta apoptoz tymotsytiv u shchuriv pislia tyreoïdektomiï.

It is found that 3 months after removal of thyroid gland in rats, a suppression of thymic endocrine function, loss of weight and cellularity occurs. These changes are mainly caused by a weakening of index of proliferative activity. In animals that postoperatively received substitutive thyroxin hormonotherapy and courses of thymulin these disorders don't occur or they are not expressed significantly.

Peptides of pineal gland and thymus prolong human life.

OBJECTIVES AND DESIGN: Researchers of the St. Petersburg Institute of Bioregulation and Gerontology of the North-Western Branch of the Russian Academy of Medical Sciences and the Institute of Gerontology of the Ukrainian Academy of Medical Sciences (Kiev) clinically assessed the geroprotective effects of thymic (Thymalin) and pineal (Epithalamin) peptide bioregulators in 266 elderly and older persons during 6-8 years. The bioregulators were applied for the first 2-3 years of observation. RESULTS: The obtained results convincingly showed the ability of the bioregulators to normalize the basic functions of the human organism, i.e. to improve the indices of cardiovascular, endocrine, immune and nervous systems, homeostasis and metabolism. Homeostasis restoration was accompanied by a 2.0-2.4-fold decrease in acute respiratory disease incidence, reduced incidence of the clinical manifestations of ischemic heart disease, hypertension disease, deforming osteoarthrosis and osteoporosis as compared to the control. Such a significant improvement in the health state of the peptide-treated patients correlated with decreased mortality rate during observation: 2.0-2.1-fold in the Thymalin-treated group; 1.6-1.8-fold in the Epithalamin-treated group; 2.5-fold in the patients treated with Thymalin plus Epithalamin as compared to the control. A separate group of patients was treated with Thymalin in combination with Epithalamin annually for 6 years and their mortality rate decreased 4.1 times as compared to the control. CONCLUSIONS: The obtained data confirmed the high geroprotective efficacy of Thymalin and Epithalamin and the expediency of their application in medicine and social care for health maintenance and age-related pathology prevention in persons over 60 to prolong their active longevity.

[Optimization of cardiovascular function by peptide bio-regulators]. / Optimizatsiia funktsii serdechno-sosudistoi sistemy peptidnymi bioreguliatorami.

Effects of peptide bioregulators (thymaline, epithalamine, cortexine) on systemic hemodynamics in cardiovascular and cerebrovascular affections were studied. Assessment of functional stability and quality of cardiovascular system regulation was made according to methodological principles of automatic regulation theory. Peptide bioregulators showed high effectiveness in the above patients who markedly improved their hemodynamic parameters.

[Effect of thymic peptides on the functional activity of phagocytic cells of donor peripheral blood]. / Vliianie timicheskikh peptidov na funktsional'nuiu aktivnost' fagotsitarnykh kletok perifericheskoi krovi donorov.

The direct action of synthetic peptide preparations, analogous to thymic hormones, on the functions of phagocytic cells was studied. The preparations Thymogen, Neogen and Thymodepressin in a dose of 10 mM produced a stimulating effect on the ingestive activity of the neutrophil, but not monocytic, population. All three preparations also enhanced the formation of oxygen metabolites registered in the luminol-dependent chemiluminescent analysis. The characteristics of spontaneous chemiluminescence (CL) reflecting the basal level of the synthesis of the active forms of oxygen and CL induced by opsomized zymosan significantly increased also in those cases when the preparations were used in a dose of 10 mM. The level of the synthesis of hydrogen peroxide in individual cells could be appraised by the intensity of the luminescence of dichlorofluorescein diacetate (DCF-DA), evaluated with the use of flow cytometry. All preparations produced a stimulating effect on the formation of hydrogen peroxide in monocytes. The reaction of neutrophils was even more active: Neogen (10 mM) produced the twofold change in the intensity of the luminescence of DCF-DA) in neutrophils, Thymogen and Thynodepressin increased the average intensity of the luminescence of DCF-DA by 80% and 60%, respectively.