The Influence of KE and EW Dipeptides in the Composition of the Thymalin Drug on Gene Expression and Protein Synthesis Involved in the Pathogenesis of COVID-19.

Thymalin is an immunomodulatory drug containing a polypeptide extract of thymus that has demonstrated efficacy in the therapy of acute respiratory distress syndrome and chronic obstructive pulmonary disease, as well as in complex therapy related to severe COVID-19 in middle-aged and elderly patients.. KE and EW dipeptides are active substances of Thymalin.

Peptide Regulation of Chondrogenic Stem Cell Differentiation.

The search for innovative ways to treat osteoarthritis (OA) is an urgent task for molecular medicine and biogerontology. OA leads to disability in persons of middle and older age, while safe and effective methods of treating OA have not yet been discovered. The directed differentiation of mesenchymal stem cells (MSCs) into chondrocytes is considered one of the possible methods to treat OA.

Feasibility of Transport of 26 Biologically Active Ultrashort Peptides via LAT and PEPT Family Transporters.

The aim of this work is to verify the possibility of transport of 26 biologically active ultrashort peptides (USPs) into cells via LAT and PEPT family transporters. Molecular modeling and computer-assisted docking of peptide ligands revealed that the size and structure of ligand-binding sites of the amino acid transporters LAT1, LAT2, and of the peptide transporter PEPT1 are sufficient for the transport of the 26 biologically active di-, tri-, and tetra-peptides. Comparative analysis of the binding of all possible di- and tri-peptides (8400 compounds) at the binding sites of the LAT and PEPT family transporters has been carried out.

Senescence-Associated Secretory Phenotype of Cardiovascular System Cells and Inflammaging: Perspectives of Peptide Regulation.

A senescence-associated secretory phenotype (SASP) and a mild inflammatory response characteristic of senescent cells (inflammaging) form the conditions for the development of cardiovascular diseases: atherosclerosis, coronary heart disease, and myocardial infarction. The purpose of the review is to analyze the pool of signaling molecules that form SASP and inflammaging in cells of the cardiovascular system and to search for targets for the action of vasoprotective peptides. The SASP of cells of the cardiovascular system is characterized by a change in the synthesis of anti-proliferative proteins (p16, p19, p21, p38, p53), cytokines characteristic of inflammaging (IL-1α,β, IL-4, IL-6, IL-8, IL-18, TNFα, TGFβ1, NF-κB, MCP), matrix metalloproteinases, adhesion molecules, and sirtuins.

Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers.

Ultrashort peptides (USPs), consisting of 2-7 amino-acid residues, are a group of signaling molecules that regulate gene expression and protein synthesis under normal conditions in various diseases and ageing. USPs serve as a basis for the development of drugs with a targeted mechanism of action. The purpose of this review is to systematize the available data on USP transport involving POT and LAT transporters in various organs and tissues under normal, pathological and ageing conditions.

Neuroepigenetic Mechanisms of Action of Ultrashort Peptides in Alzheimer's Disease.

Epigenetic regulation of gene expression is necessary for maintaining higher-order cognitive functions (learning and memory). The current understanding of the role of epigenetics in the mechanism of Alzheimer's disease (AD) is focused on DNA methylation, chromatin remodeling, histone modifications, and regulation of non-coding RNAs. The pathogenetic links of this disease are the misfolding and aggregation of tau protein and amyloid peptides, mitochondrial dysfunction, oxidative stress, impaired energy metabolism, destruction of the blood-brain barrier, and neuroinflammation, all of which lead to impaired synaptic plasticity and memory loss.

Peptides Regulating Proliferative Activity and Inflammatory Pathways in the Monocyte/Macrophage THP-1 Cell Line.

This study evaluates the effects of five different peptides, the Epitalon tetrapeptide, the Vilon dipeptide, the Thymogen dipeptide, the Thymalin peptide complex, and the Chonluten tripeptide, as regulators of inflammatory and proliferative processes in the human monocytic THP-1, which is a human leukemia monocytic cell line capable of differentiating into macrophages by PMA in vitro. These peptides (Khavinson Peptides), characterized by Prof. Khavinson from 1973 onwards, were initially isolated from animal tissues and found to be organ specific.

Peptide Regulation of Gene Expression: A Systematic Review.

Peptides are characterized by their wide range of biological activity: they regulate functions of the endocrine, nervous, and immune systems. The mechanism of such action of peptides involves their ability to regulate gene expression and protein synthesis in plants, microorganisms, insects, birds, rodents, primates, and humans. Short peptides, consisting of 2-7 amino acid residues, can penetrate into the nuclei and nucleoli of cells and interact with the nucleosome, the histone proteins, and both single- and double-stranded DNA.

Homology between SARS CoV-2 and human proteins.

An extremely high contagiousness of SARS CoV-2 indicates that the virus developed the ability to deceive the innate immune system. The virus could have included in its outer protein domains some motifs that are structurally similar to those that the potential victim's immune system has learned to ignore. The similarity of the primary structures of the viral and human proteins can provoke an autoimmune process.

Neuroprotective Effects of Tripeptides-Epigenetic Regulators in Mouse Model of Alzheimer's Disease.

KED and EDR peptides prevent dendritic spines loss in amyloid synaptotoxicity in in vitro model of Alzheimer's disease (AD). The objective of this paper was to study epigenetic mechanisms of EDR and KED peptides' neuroprotective effects on neuroplasticity and dendritic spine morphology in an AD mouse model. Daily intraperitoneal administration of the KED peptide in 5xFAD mice from 2 to 4 months of age at a concentration of 400 μg/kg tended to increase neuroplasticity.

EDR Peptide: Possible Mechanism of Gene Expression and Protein Synthesis Regulation Involved in the Pathogenesis of Alzheimer's Disease.

The EDR peptide (Glu-Asp-Arg) has been previously established to possess neuroprotective properties. It activates gene expression and synthesis of proteins, involved in maintaining the neuronal functional activity, and reduces the intensity of their apoptosis in in vitro and in vivo studies. The EDR peptide interferes with the elimination of dendritic spines in neuronal cultures obtained from mice with Alzheimer's (AD) and Huntington's diseases.

Peptides: Prospects for Use in the Treatment of COVID-19.

There is a vast practice of using antimalarial drugs, RAS inhibitors, serine protease inhibitors, inhibitors of the RNA-dependent RNA polymerase of the virus and immunosuppressants for the treatment of the severe form of COVID-19, which often occurs in patients with chronic diseases and older persons. Currently, the clinical efficacy of these drugs for COVID-19 has not been proven yet. Side effects of antimalarial drugs can worsen the condition of patients and increase the likelihood of death.

Towards realization of longer life.

The current demographic situation in the world is characterized by an increase in average life expectancy, low birth rate, as well as an increase in the number of older and senior people, which is why our epoch is referred to as «the age of ageing». [..

Gene expression in human mesenchymal stem cell aging cultures: modulation by short peptides.

Effects of the short peptides Ala-Glu-Asp (AED), Lys-Glu-Asp (KED) and Lys-Glu (KE) on the expression of IGF1, FOXO1, TERT, TNKS2, and NFκB genes were studied in human embryo bone marrow mesenchymal stem cells (line FetMSCs) variously aged in "passages" or "stationary" cultures. Both cell aging models were similar in gene expression. The main difference was in the TERT gene expression level, which showed an eightfold increase at the "stationary" aging.

AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism.

It was shown that AEDG peptide (Ala-Glu-Asp-Gly, Epitalon) regulates the function of the pineal gland, the retina, and the brain. AEDG peptide increases longevity in animals and decreases experimental cancerogenesis. AEDG peptide induces neuronal cell differentiation in retinal and human periodontal ligament stem cells.

Peptide Regulation of Cell Differentiation.

Short peptides are molecules with small molecular weight, capable of penetrating the cell membrane and nuclear membrane for epigenetic regulation of gene expression, including the genes responsible for cell differentiation. The direction of cell differentiation induction depends on the peptide structure and concentration. AEDG and AEDP peptides induce differentiation of pluripotent cells in the epidermis, mesenchyme and nervous tissue.

Short Peptides Protect Oral Stem Cells from Ageing.

Primary stem cells, after several cell divisions, enter into a senescence state, that is characterized by alterations to spindle-shape typical morphology. This concern is one of the main problems in the use of human mesenchymal stem cells (hMSCs) in clinical applications which demand cells in large numbers. Short peptides had geroprotective properties and stimulated stem cell differentiation.

Systematic search for structural motifs of peptide binding to double-stranded DNA.

A large variety of short biologically active peptides possesses antioxidant, antibacterial, antitumour, anti-ageing and anti-inflammatory activity, involved in the regulation of neuro-immuno-endocrine system functions, cell apoptosis, proliferation and differentiation. Therefore, the mechanisms of their biological activity are attracting increasing attention not only in modern molecular biology, biochemistry and biophysics, but also in pharmacology and medicine. In this work, we systematically analysed the ability of dipeptides (all possible combinations of the 20 standard amino acids) to bind all possible combinations of tetra-nucleotides in the central part of dsDNA in the classic B-form using molecular docking and molecular dynamics.

Effect of short peptides on neuronal differentiation of stem cells.

It has been demonstrated that short peptides play an important role in the transmission of biological information, modulation of transcription, and restoring genetically conditioned alterations occurring with age. Peptidergic regulation of homeostasis occupies an important place in physiological processes, which lead to the aging of cells, tissues, and organs, consisting in the involution of major regulatory systems-the nervous, the endocrine, and the immune. The effect of AED (Ala-Glu-Asp), KED (Lys-Glu-Asp), KE (Lys-Glu), AEDG (Ala-Glu-Asp-Gly) peptides and their compound on neuronal differentiation of human periodontal ligament stem cells (hPDLSCs) was studied by immunofluorescence and western blot analysis.

"I think that the small peptides are the best for healthy ageing...", an interview with Vladimir Khavinson. Interview by Suresh I. S. Rattan.

Since its inception in 2000, Biogerontology has published interviews with some of the most renowned and intellectually influential biogerontologists, including Len Hayflick, Robin Holliday, Denham Harman, Vincent Cristofalo, Claudio Franceschi, Leslie Robert, Ken Kitani, Geroge Martin, Zhores Medvedev and John Maynard Smith. These interviews have explored the minds of these scientists in all aspects of their lives combining the private and the professional. Together, this series is a remarkable document providing an insight into the history of ideas in modern biogerontology.

Pinealon protects the rat offspring from prenatal hyperhomocysteinemia.

The offspring of rats with experimental hyperhomocysteinemia caused by alimentary loading with dietary methionine within pregnancy has been studied. Using pinealon (Glu-Asp-Arg) under these conditions was found to result in the offspring cognitive function being improved significantly and their cerebellum neurons becoming more resistant to oxidative stress. This may be proved by the fact that the administration of pinealon to pregnant rats loaded with methionine improved their offspring spatial orientation and learning ability and decreased both reactive oxygen species accumulation and the number of necrotic cells in the population of the neurons isolated from the cerebellum of the offspring developed under the prenatal hyperhomocysteinemia.

Biogerontology in Russia: from past to future.

The paper presents major steps of gerontology development in Russia. The issues of training in gerontology and geriatrics, institutional infrastructure within the Gerontological Society of the Russian Academy of Sciences and its activities have been considered therein. Some results of Russian researchers obtained during 2005-2010 have been summarized as well.

Peptide bioregulation of aging: results and prospects.

The review comprises the results of author's long-term investigation in the mechanisms of aging and a role of peptide bioregulators in prevention of age-related pathology. A number of small peptides have been isolated from different organs and tissues and their analogues (di-, tri-, tetrapeptides) were synthesized from the amino acids. It was shown that long-term treatment with some peptide preparations increased mean life span by 20-40%, slow down the age-related changes in the biomarkers of aging and suppressed development of spontaneous and induced by chemical or radiation carcinogens tumorigenesis in rodents.

DNA double-helix binds regulatory peptides similarly to transcription factors.

Problem: Gerontology observations show that ageing of organism is accompanied by the decrease of the chromatin activity and slowing down of the protein synthesis. Natural regulatory oligopeptides and their synthetic analogues take part in the activation of chromatin and normalise rate of the protein synthesis in cultured tissues. Regulatory peptides significantly enhance longevity.