ARID1A, Prostaglandin E2, and Its Receptor as Possible Predictors of Malignant Transformation of the Endometrium in Endometriosis.

We studied the expression of ARID1A, prostaglandin E2 synthase, and prostaglandin E2 receptor in the endometrium and ovarian, peritoneal, and intestinal endometrioid heterotopies in women with endometriosis of young and middle reproductive age. ARID1A protein is a tumor suppressor, its expression reduced in different types of cancer. Prostaglandin E2 synthase and prostaglandin E2 receptor are involved in the signaling cascade of inflammatory reactions presumably underlying the development of endometriosis. In endometrioid heterotopies, expression of ARID1A was reduced in 1.2-4.0 times, the expression of prostaglandin E2 synthase and prostaglandin E2 receptor was reduced in 2.9-5.2 times These findings suggest that ARID1A, prostaglandin E2 synthase, and prostaglandin E2 receptor can be used as predictors of malignant transformation of endometrioid heterotopies in women with endometriosis.

[Epigenetic Mechanisms of Peptide-Driven Regulation and Neuroprotective Protein FKBP1b].

Cortexin is a clinically approved cerebral cortex polypeptide complex in calves. The mechanism of cortexin action is not understood well. Two cortexin derivatives, short peptides EDR and DS with neuroprotective activity, were synthesized. According to the data of molecular modeling, these peptides are able to bind to the histone H1.3 protein. This can affect the conformation of histone H1.3, which leads to a change in the chromatin structure in the loci of some genes, in particular Fkbp1b encoding the FK506-binding protein. Electrophysiological processes associated with the Ca^(2+) exchange are disturbed in the pyramidal neurons of the hippocampus during aging of the brain. The Fkbp1b gene encodes peptidyl-prolyl cis-trans isomerase, regulating the release of calcium ions from the sarcoplasmic and endoplasmic reticulum of neurons. The activation of the Fkbp1b gene transcription under treatment with short peptides can promote the synthesis of its protein product and the activation of the Ca^(2+) release from organelles of the sarcoplasmic and endoplasmic reticulum of neurons, which, in turn, can lead to an increase in the functional activity of neurons.

Expression of Aß42, τ-Protein, p16, p53 in Buccal Epithelium: Prospects for Use in the Diagnostics of Alzheimer's Disease and Rate of Aging.

The expression of Aß42, and τ-protein, and p16 and p53 proteins was analyzed in the buccal epithelium of elderly and senile patients with Alzheimer's disease. We revealed enhanced synthesis of Alzheimer's disease markers Aß42 (by 15-30 times) and τ-protein (by 5 times) in comparison with the corresponding values in people without neurodegenerative pathology of the same age groups. In addition, increased synthesis of proteins of cell aging and apoptosis p16 (by 6-10 times) and p53 (by 2-3 times) was observed in patients in comparison with age-matched persons without neuropathology. These data suggest that complex analysis of the expression of Aß42, τ-protein, p16, and p53 in the buccal epithelium is a promising method for in vivo diagnosis of Alzheimer's disease and assessment of the rate of aging during the development of this pathology.

Identification of Peptide AEDG in the Polypeptide Complex of the Pineal Gland.

The polypeptide complex of the epiphysis and the peptide AEDG, constructed on the basis of its amino acid analysis, exert similar biological effects. Both bioregulators normalize melatonin synthesis in the pineal gland, functioning of the brain, eye retina, cardiovascular, endocrine, and immune systems; they also act as antioxidants, stress-protectors, and geroprotectors. Within the epiphysis polypeptide complex, free amino acids (3.26%), dipeptides (23.19%), tripeptides (50.72%), tetrapeptides (22.10%), and pentapeptides (0.72%) were revealed by mass spectrometry and HPLC. Peptide AEDG was detected among the tetrapeptides of the epiphysis polypeptide complex by selective reaction monitoring method. The biological effects of the epiphysis polypeptide complex are determined by the effect of its component AEDG.

Role of LIF Cytokine and CD34 Angiogenesis Marker in Non-Developing Pregnancy.

The expression of cytokine LIF (leukemia inhibiting factor) in the endometrium of women of young reproductive age with non-developing pregnancy of unknown genesis is higher than in older women and women with infection-related miscarriages by 1.26 and 1.43 times, respectively. The expression of angiogenesis marker CD34 in the endometrium of young women with non-developing pregnancy of unknown origin is 1.59 times higher and in case of endometrial inflammation 1.31 times higher than in women of the older reproductive age with the same disease. Correlation between the endometrial expression of LIF and CD34 is detected in women of the younger reproductive age with non-developing pregnancy of unknown etiology. The expression of LIF and CD34 can be used for endometrial function evaluation in women of different age with first trimester non-developing pregnancy.

Tripeptides Restore the Number of Neuronal Spines under Conditions of In Vitro Modeled Alzheimer's Disease.

In primary culture of mouse hippocampal neurons, peptide EDR (200 ng/ml) under conditions of amyloid synaptotoxicity (a model of Alzheimer's disease) increased the number of mushroom spines by 71% and returned this parameter to the normal level. Under the same conditions, tripeptide KED (200 ng/ml) increased the number of mushroom spines in hippocampal neurons by 20%. Tripeptide EDR can be recommended for further experimental study as a candidate neuroprotective agent for prevention and treatment of Alzheimer's disease.

Nephroprotective Effect of EDL Peptide at Acute Injury of Kidneys of Different Genesis.

EDL peptide produced a nephroprotective effect on experimental models gentamycin-induced nephropathy and ischemia/reperfusion kidney injury in rats. The nephroprotective effect of EDL peptide manifested in prevention of oliguria and retention azotemia, a decrease in proteinuria and sodium excretion, prevention of critical decrease in activities of antioxidant enzymes, suppression of LPO, and normalization of energy supply to kidneys cells. Our findings confirm the prospects of further studies of the nephroprotective properties of peptide EDL in various pathologies of the kidneys.

Effect of Polypeptides on Cell Proliferation and Apoptosis during Aging.

Polypeptide complexes derived from the bronchi, blood vessels, muscles, kidneys, ovaries, testes, and retina stimulated the processes of cell renewal in organotypic cultures of the corresponding organs of young and old animals. A correlation between the intensity of regeneration and animal' age was revealed. The polypeptide complexes reduced the expression of apoptotic factors p53 and caspase 3 and increased the expression of proliferation protein Ki-67. These results provide the basis for further study of the polypeptide complexes as stimulators of regenerative processes in different tissues during ageing.

Short Peptides Regulate Gene Expression.

Short peptides constitute the system of signal molecules regulating the functions of the organism at the molecular, genetic, subcellular, cellular, and tissue levels. One short peptide can regulate dozens of genes, but the molecular mechanism of this process remains unclear. We suppose that short peptides penetrate through the cytoplasmic and nuclear membrane and bind to DNA. Spatial models of DNA-peptide complexes are constructed for 19 short peptides by the docking method. Some peptides have the same binding sites. Peptides KE and EDP bind agat sequence, peptides KEDW and AED to acct sequence, and peptides AEDL and EDL to ctcc sequence.

Short Peptides and Telomere Length Regulator Hormone Irisin.

Irisin produced by muscles during exercise and promoting fat burning also exhibits geroprotective effect and induces telomere elongation in normal somatic cells. Special attention is paid to studies of the role of peptides Lys-Glu, Glu-Asp-Arg, and Ala-Glu-Asp-Gly in epigenetic regulation of irisin content. The data suggest that the immunomodulatory peptide Lys-Glu and neuroprotective peptide Glu-Asp-Arg modulate the life span by modulating irisin gene expression.

Peptides Restore Functional State of the Kidneys During Cisplatin-Induced Acute Renal Failure.

The effects of polypeptide complex from the kidney and short peptides AED, EDL, and AEDG on renal functions were studied in rats with cisplatin-induced acute renal failure. AED peptide decreased protein excretion and electrolyte concentration in the urine. Polypeptide complex from the kidney and peptides EDL and AEDG normalized diuresis, creatinine concentration in the urine and its excretion, glomerular filtration rate, and absolute resorption of sodium ions and reduced protein concentration in the urine and its excretion, the concentrations of sodium and potassium ions in the urine, and other parameters. EDL peptide produced was potent nephroprotective effect. It is known that the polypeptide complex of the kidney and short peptides restore the expression of signal molecules (marker of functional state of the kidneys), so these peptide substances can have nephroprotective effect during various renal pathologies.

[INFLUENCE OF MILLIMETER-WAVE ELECTROMAGNETIC EMISSION ON NITRIC OXIDE SYNTHESIS DURING VESSEL ENDOTHELIUM AGING IN VITRO].

The applying of millimeter-wave electromagnetic emission (EHF-therapy) is an effective method for various age-related pathologies treatment, among other cardio-vascular diseases. During the EHF-emission of aging human endothelial cell cultures it was obtained changing of NO-synthase (eNOS), endothelin-1, angiotensin-2 and vasopressin expression dependence of irradiation exposition. These data have shown that EHF-emission has activated endothelium functional activity, which can play the important role to search for approaches to treatment of arterial hypertension and atherosclerosis.

[POLYPEPTIDES INFLUENCE ON TISSUE CELL CULTURES REGENERATION OF VARIOUS AGE RATS].

A comparative study of polypeptides extracted from the tissues of calves: Cortexin (from brain cortex), Epinorm (from pineal gland), Ventvil (from liver), Prostatilen (from prostate), Thymalin (from thymus), Chelohart (from heart), Chondrolux (from cartilage) on the relevant organotypic tissue cultures of young and old rats, in concentration 0,01-100 ng/ml was performed. Polypeptides specifically stimulated "young" and "old" cell cultures growth in concentration 20-50 ng/ml. This effect correlates with increasing of PCNA and decreasing of p53 expression in brain cortex, pineal gland, liver, prostate, heart, cartilage. Moreover, Thymalin activated CD5, CD20 expression--markers of B-cells differentiation. These data show that polypeptides isolated from different tissues have selective molecular activity on the regeneration of suitable tissues in aging.

Peptide Regulation of Cells Renewal Processes in Kidney Tissue Cultures from Young and Old Animals.

Polypeptide complex isolated from calf kidneys stimulates the processes of cell renewal in organotypic kidney tissue cultures from young and old rats. The polypeptide complex enhances expression of proliferation marker Ki-67 and reduces expression of proapoptotic peptide p53 in kidney explants obtained from young and old animals. Short peptides T-31 (AED) and T-35 (EDL) also stimulate proliferation and reduce apoptosis of the kidney cells, but to a lesser degree than the polypeptide complex. The results provide the basis for further investigation of the polypeptide complex as a preparation for the therapy of kidney diseases, including age-related pathologies.

[Molecular-physiological aspects of peptide regulation of function of the retina in retinitis pigmentosa].

Peptide's bioregulators promotes restoration of the physiological activity of the retina in retinitis pigmentosa in older adults and in animal models. The molecular mechanism of physiological activity of peptides is connected with its ability to regulate synthesis of protein markers of differentiation of neurons and retinal pigment epithelium epigenetically.

Peptides stimulate expression of signal molecules in neuronal cultures from animals of different age.

Molecular mechanisms of the neuroprotective effect of peptide T-33 and cortexin were studied on organotypic cultures of the brain from young and old Wistar rats. The effective concentration of peptide T-33 stimulating proliferative activity of neurons considerably surpassed that of cortexin. Cortexin and peptide T-33 stimulated the expression of serotonin, Ki-67, and vimentin in cells of the brain cortex; peptide T-33 was most effective in this respect.

[Epigenetic aspects of peptidergic regulation of vascular endothelial cell proliferation during aging].

Short peptides vesugen and D-7 have stimulated proliferation-associated protein Ki-67 decreased during aging in tissue-specific cell cultures received from young and old animals and in dissociated vascular endothelial cell cultures. Peptides vesugen and D-7 have interacted with promoter region of MKI67 gene coding protein Ki-67 that was obtained using methods of molecular docking. Both peptides have contacted with core promoter 5'-agcctcaaccatcaggaaaacaagagt-3' located in MKI67 gene from -14 to +12 base pairs relative to the transcriptional initiation site through sequence CATC(ENSG00000148773). Thus, vasoprotective effect of peptide vesugen revealed previously in elder people could be realized through epigenetic regulation of Ki-67 gene expression.

Peptides regulate expression of signaling molecules in kidney cell cultures during in vitro aging.

We studied the effect of polypeptide complex isolated from calf kidney and short peptides T-31 (AED) and T-35 (EDL) on the expression of signaling molecules, markers of cell renewal (Ki-67, p53), remodeling of the extracellular matrix (MMP-14), and immune response (IL-8) in primary kidney cell cultures during aging. The complex of renal polypeptides and T-31 peptide activate cell renewal processes during aging of the renal epithelium, while gelatinase MMP-14 is the target of T-35 peptide.

[Molecular aspects of renal desease].

The review considers molecular mechanisms of chronic renal failure and cancer kidney disease. The most important molecules inducing inflammation are cytokines (MCP-1, TNFalpha, IFN-gamma, IL-1,6,8,18), matrix metalloproteinases MMP-2,3,9,14, tissue inhibitors of metalloproteinases (TIMPs) and grow factors (VEGF PDGE FGF). This signal molecules regulate the activity of immune cells and remodeling extracellular matrix (ECM) components taken place in inflammatory reactions, proliferation, apoptosis and also in the differentiation of kidney cells. On the basis of these data nowadays developed new highly selective approaches to diagnosis, prediction, estimation of efficiency of treatment of renal disease and creating of target drugs.

[Tripeptides slow down aging process in renal cell culture].

The mechanism of geroprotective effect of peptides AED and EDL was studied in ageing renal cell culture. Peptide AED and EDL increase cell proliferation, decreasing expression of marker of aging p16, p21, p53 and increasing expression of SIRT-6 in young and aged renal cell culture. The reduction of SIRT-6 synthesis in cell is one of the causes of cell senescence. On the basis of experimental data models of interaction of peptides with various sites of DNA were constructed. Both peptides form most energetically favorable complexes with d(ATATATATAT)2 sequences in minor groove of DNA. It is shown that interaction of peptides AED and EDL with DNA is the cause of gene expression, encoded marker of ageing in renal cells.