Toll like receptors TLR1/2, TLR6 and MUC5B as binding interaction partners with cytostatic proline rich polypeptide 1 in human chondrosarcoma.

Metastatic chondrosarcoma is a bone malignancy not responsive to conventional therapies; new approaches and therapies are urgently needed. We have previously reported that mTORC1 inhibitor, antitumorigenic cytostatic proline rich polypeptide 1 (PRP-1), galarmin caused a significant upregulation of tumor suppressors including TET1/2 and SOCS3 (known to be involved in inflammatory processes), downregulation of oncoproteins and embryonic stem cell marker miR-302C and its targets Nanog, c-Myc and Bmi-1 in human chondrosarcoma. To understand better the mechanism of PRP-1 action it was very important to identify the receptor it binds to.

Stroke burden in adults in Armenia.

We investigated around 100 patients for one-year and then registered the information about the possible etiology of the stroke, type of disease, treatment, localization of the clot, age, as well as gender distribution of stroke patients' population. This general overview of risk factors, ways of treatment, diagnostics, care and monitoring of the stroke patients in Armenia might serve as a cornerstone work for further highlighting of new avenues for stroke treatment.

mTORC1 inhibition and ECM-cell adhesion-independent drug resistance via PI3K-AKT and PI3K-RAS-MAPK feedback loops.

Mammalian target of rapamycin (mTOR) serine threonine kinase is the enzyme that regulates cancer cell growth by altering nutrient supplies to cancer cells. The neuropeptide (proline-rich peptide 1 (PRP-1)), galarmin, produced by the brain neurosecretory cells is a mTOR kinase inhibitor with powerful 80% antiproliferative cytostatic effect in a high-grade chondosarcoma and other mesenchymal tumors. However, the negative feedback loop of phosphatidylinositol 3 kinase-Protein kinase B (PKB), PI3K-AKT and PI3K-rat sarcoma (RAS)-mitogen-activated protein kinase (MAPK) activation is well documented for mTOR inhibitors.

The influence of hypothalamic cytokine PRP on protein synthesis in brain subcellular compartments in crush syndrome.

Crush-syndrom (CS) was characterized by Bywaters E.G.L.

Neuroprotective action of proline-rich polypeptide-1 in β-amyloid induced neurodegeneration in rats.

It is recognized that the main trigger of Alzheimer disease related neurodegeneration is β-amyloid peptide, which subsequently generates different metabolic disorders in neuron and finally leads to neuronal death. Several biologically active products were tested as neuroprotectors, but only few of them demonstrated any efficiency. Proline-rich polypeptide-1 was tested as a neuroprotective agent on Aβ25-35 animal model of Alzheimer disease.

Cytostatic effect of novel mTOR inhibitor, PRP-1 (galarmin) in MDA 231 (ER-) breast carcinoma cell line. PRP-1 inhibits mesenchymal tumors.

Activation of the PI3K-Akt-mTOR pathway is implicated both in the establishment of tumors and as well as a target for therapy in many types of solid malignancy, its blockade represents an opportunity to improve outcomes in patients with tumors that are associated with poor prognosis. Our experimental data indicates that proline-rich polypeptide-1 (PRP-1, galarmin) is immunomodulator cytokine, produced by hypothalamic neurosecretory cells and exerts its antiproliferative effect on the tumor cells of mesenchymal origin via inhibiting mTOR kinase activity and repressing cell cycle progression. The goal of these investigations was to elucidate the antiproliferative action of PRP-1 on the breast carcinoma cell line MDA 231 (ER-) and to compare PRP-1 action previously reported on other mesenchymal tumors.

Cytostatic effect of the hypothalamic cytokine PRP-1 is mediated by mTOR and cMyc inhibition in high grade chondrosarcoma.

This study aimed to further elucidate the molecular mechanisms of antiproliferative action of proline rich polypeptide 1 (PRP-1) cytokine, produced by neurosecretory cells of the hypothalamus to be considered as alternative adjuvant therapy for metastatic chondrosarcoma, which does not respond to chemotherapy or radiation and currently without any effective treatment. Rapid cell proliferation assay of human primary cultures from high grade chondrosarcoma patients biopsies and human chondrosarcoma JJ012 cell line indicated 50 and 80% inhibition in PRP-1 treated samples correspondingly. Videomicroscopy detected that despite the treatment there are still dividing cells, meaning that cells are not in the state of dormancy, rather PRP-1 repressed the cell cycle progression, exhibited cytostatic effect.

Concepts of neuroendocrine cardiology and neuroendocrine immunology, chemistry and biology of signal molecules.

Discovery of neurosecretion of cardioactive neurohormones produced by hypothalamic nuclei (NSO and NPV), as well as the biosynthesis of several immunomodulators (signal molecules of the neuroendocrine immune system of brain), deciphering of their chemical structure and study of their biological properties led to the foundation of two important trends of neurobiology: neuroendocrine immunology and cardiology. Hormone formation by atrium ganglionary nerve cells and auriculum establishment of neurohumoral interactions between hypothalamic and atrium neurosecretion indicated the existence of the system neuroendocrine hypothalamus--endocrine heart. Study of their biological properties promoted creation of powerful neurohormonal preparations for the treatment of immune, cardio-vascular, neurodegenerative, infectious and tumor diseases.

Proline-rich cytokine from neurosecretory granules: a new natural substrate for dipeptidyl peptidase IV.

A proline-rich cytokine from neurosecretory granules of bovine neurohypophysis, 15 amino acids containing PRP-1 (Ala-Gly-Ala-Pro-Glu-Pro-Ala-Glu-Pro-Ala-Gln-Pro-Gly-Val-Tyr), had been demonstrated as a unique regulator of activity of neurons, strong antibacterial agent, and mediator of the hypothalamus-neurohypophysis-bone marrow-thymus axis, which participates in hematopoietic stem cells differentiation. In the present work it was shown that this neuropeptide represents a new natural substrate for Dipeptidyl Peptidase IV (DPPIV). The time-dependent increase of primary amines quantity in the assay mixture of PRP-1 and DPPIV has been observed allowing to conclude, that DPPIV catalyses the enzymatic reaction of PRP-1 cleavage.

Protective effects of hypothalamic proline-rich peptide and cobra venom Naja Naja Oxiana on dynamics of vestibular compensation following unilateral labyrinthectomy.

We tested the action of proline-rich peptide (PRP-1) and cobra venom Naja Naja Oxiana (NOX) on Deiters' nucleus neurons at 3rd, 15th and 35th days after unilateral labyrinthectomy (UL). Early and late tetanic, post-tetanic potentiation and depression of Deiters'neurons to bilateral high frequency stimulation of hypothalamic supraoptic and paraventricualar nuclei was studied. The analysis of spike activity was carried out by mean of on-line selection and special program.

Proline-rich hypothalamic polypeptide has opposite effects on the proliferation of human normal bone marrow stromal cells and human giant-cell tumour stromal cells.

In the present study we carried out experiments in vitro and in vivo and investigated the effect of proline-rich polypeptide (PRP) on the proliferation and effectiveness of colony formation of MMSCs in vitro. Various routes and doses of PRP administration to rats increased the number of MMSCs in bone marrow and spleen. Our research revealed opposite effects of PRP on the proliferation of bone marrow stromal cells obtained from normal humans and stromal cells isolated from a human giant-cell tumour.

Hypothalamic proline rich polypeptide regulates hematopoiesis.

The AGAPEPAEPAQPGVY proline-rich polypeptide (PRP-1) was isolated from neurosecretory granules of the bovine neurohypophysis; it is produced by N. supraopticus and N. paraventricularis.

Antitumorigenic effect of brain proline rich polypeptide-1 in human chondrosarcoma.

Proline rich polypeptide (PRP-1) produced by neurosecretory cells of the hypothalamus is one of the fragments of neurophysin-vasopressin-associated glycoprotein. The primary structure of the neuropeptide PRP-1 isolated from neurosecretory granules of bovine neurohypophysis. We investigated PRP-1 action on chondrosarcoma, the second most common malignancy in bone, which primarily affects the cartilage cells.

Comparative effects of atrial polypeptide and neurohormone C on the interaction of factor Xa with antithrombin III.

The effects of atrial polypeptide and neurohormone C upon the interaction of human factor Xa (FXa) and human antithrombin III (ATIII) were followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. A pattern of bands consisting of a 1 degree duplex complex (FXaalpha-ATIII band of 109 kDa, FXabeta-ATIII band of 104 kDa), a 2 degree duplex complex (alpha band of 99 kDa, beta band of 95 kDa), a 3 degree duplex complex (alpha band of 66 kDa, beta band of 62 kDa), modified ATIII (ATIIIM, 58 kDa), native ATIII (55 kDa), FXaalpha (52 kDa), FXabeta (47 kDa), and a FXa degradation product (FXagamma, 35 kDa) was detected and quantitated. Preincubation of FXa, ATIII, or mixtures thereof with atrial polypeptide produced a shift from FXaalpha-ATIII to FXabeta-ATIII complexes and increases in both ATIIIM and FXagamma, reflecting degradation of the 1 degree and 2 degree complex to form the 3 degree complex.

Neuroprotection by hypothalamic peptide proline-rich peptide-1 in Abeta25-35 model of Alzheimer's disease.

Background: This work sought to determine the effects of hypothalamic proline-rich peptide (PRP)-1 in a rat model of Alzheimer's disease.

Methods: Complex histochemical, electrophysiologic, and behavioral analyses were performed on intact or diseased Wistar rats (n = 28). Pathologic conditions were induced by bilateral intracerebroventricular injection of amyloid peptide Abeta25-35.

Myc-oncogene inactivating effect by proline rich polypeptide (PRP-1) in chondrosarcoma JJ012 cells.

Proline rich polypeptide (PRP-1) produced by NPV and NSO cells is released into the general circulation and exerts its effect on the activity of immunocompetent and neuronal cells. PRP-1 is a unique regulator of hematopoiesis, stimulator of bone-marrow hematogenesis. Taking into consideration our preliminary data on antitumor and unique diverse biological properties of PRP-1 previously described by Galoyan et al.

Effect of hypothalamic proline-rich peptide (PRP-1) on neuronal and bone marrow cell apoptosis.

The AGAPEPAEPAQPGVY proline-rich peptide (PRP-1) was isolated from neurosecretory granules of the bovine neurohypophysis; it is produced by N. supraopticus and N. paraventricularis.

Synthetic bovine proline-rich-polypeptides generate hydroxyl radicals and fail to protect dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity in mice.

Proline-rich-polypeptides (PRPs) isolated from bovine hypothalamus have been shown to render protection against neuronal injury of the brain and spinal cord. We examined two PRPs containing 15 and 10 amino acid residues (PRP-1 and PRP-4 synthetic polypeptide) for their effect, if any, on dopaminergic neuronal damage caused by the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Effects of these PRPs on hydroxyl radical ((*)OH) generation in a Fenton-like reaction as well as from isolated mitochondria were monitored, employing a sensitive salicylate hydroxylation procedure.

Hypothalamic proline-rich polypeptide is a regulator of oxidative burst in human neutrophils and monocytes.

Objective: The effects of proline-rich polypeptide (PRP) isolated from neurosecretory granules of bovine neurohypophysis produced by nuclei supraopticus and paraventricularis on phagocytosis, bacterial intracellular killing and oxidative burst induction in normal human cells and inflammatory cells from patients with Behçet's disease (BD), i.e. peripheral blood neutrophils and monocytes, were investigated.

Neuroprotective action of hypothalamic peptide PRP-1 at various time survivals following spinal cord hemisection.

The purpose of the present study was to evaluate the neuroprotective action of proline-rich peptide-1 (PRP-1) produced by hypothalamic nuclei cells (nuclei paraventricularis and supraopticus) following lateral hemisection of spinal cord (SC). The dynamics of rehabilitative shifts were investigated at various periods of postoperative survival (1-2, 3, and 4 weeks), both with administration of PRP-1 and without it (control). We registered evoked spike flow activity in both interneurons and motoneurons of the same segment of transected and symmetric intact sides of SC and below it on the stimulation of mixed (n.

PRP-1 protective effect against central and peripheral neurodegeneration following n. ischiadicus transection.

We investigated the action of the new hypothalamic proline-rich peptide (PRP-1), normally produced by neurosecretory cells of hypothalamic nuclei (NPV and NSO), 3 and 4 weeks following rat sciatic nerve transection. The impulse activity flow of interneurons (IN) and motoneurons (MN) on stimulation of mixed (n. ischiadicus), flexor (n.

Hypothalamic proline-rich polypeptide is an oxidative burst regulator.

The AGAPEPAEPAQPGVY proline-rich polypeptide (PRP) was isolated from neurosecretory granules of the bovine neurohypophysis; it is produced by N. supraopticus and N. paraventricularis.

A synthetic human proline-rich-polypeptide enhances hydroxyl radical generation and fails to protect dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced toxicity in mice.

Some of the proline-rich-polypeptides (PRPs) are shown to afford protection against spinal cord transection or crush syndrome-induced neurodegeneration in the brain. In the present study a synthetic proline-rich-polypeptide of human hypothalamus origin (h-PRP) has been examined for its potency to protect against dopaminergic neuronal damage caused by the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Effect of h-PRP on hydroxyl radical (*OH) generation in a Fenton-like reaction was monitored, employing a sensitive salicylate hydroxylation procedure.

Survival of trauma-injured neurons in rat brain by treatment with proline-rich peptide (PRP-1): an immunohistochemical study.

The objective of this immunohistochemical research was to reveal the distribution of a proline-rich peptide-1 (PRP-1) in various brain structures of intact and trauma-injured rats and to identify the mechanisms of promotion of neuronal recovery processes following PRP-1 treatment. PRP-1, produced by bovine hypothalamic magnocellular cells and consisting of 15 amino acid residues, is a fragment of neurophysin vasopressin associated glycoprotein isolated from bovine neurohypophysis neurosecretory granules. PRP-1-immunoreactivity (PRP-1-IR) was detected in the brain of intact rats in the neurons of paraventricular (PVN) and supraoptic (SON) nuclei in the hypothalamus, in almost all cell groups in the medulla oblongata, in Purkinje and some cerebellar nuclei cells, and in nerve fibers.