Features of Intracellular Signal Transduction in Neural Stem Cells under the Influence of Alkaloid Songorine, an Agonist of Fibroblast Growth Factor Receptors.

We performed a comparative in vitro study of the involvement of NF-κB, PI3K, cAMP, ERK1/2, p38, JAKs, STAT3, JNK, and p53-dependent intracellular signaling in the functioning of neural stem cells (NSC) under the influence of basic fibroblast growth factor (FGF) and FGF receptor agonist, diterpene alkaloid songorine. The significant differences in FGFR-mediated intracellular signaling in NSC were revealed for these ligands. In both cases, stimulation of progenitor cell proliferation occurs with the participation of NF-κB, PI3K, ERK1/2, JAKs, and STAT3, while JNK and p53, on the contrary, inhibit cell cycle progression. However, under the influence of songorin, cAMP- and p38-mediated cascades are additionally involved in the transmission of the NSC division-activating signal. In addition, unlike FGF, the alkaloid stimulates progenitor cell differentiation by activating ERK1/2, p38, JNK, p53, and STAT3.

Antitoxic Activity of Extract from Salix Viminalis Leaves under Conditions of 5-Fluorouracil Treatment.

Injection of 5-fluorouracil to animals caused a pronounced toxic effect. Therapeutic and preventive treatment with Salix viminalis leaf extract significantly reduced the negative effects of the antitumor drug: promoted recovery of the bone marrow, peripheral blood, and visceral parameters and prevented ulceration. Combined use of the cytostatic and Salix viminalis extract increased the efficiency of antitumor therapy.

Role of cAMP- and IKK-2-Dependent Signaling Pathways in Functional Stimulation of Mesenchymal Progenitor Cells with Alkaloid Songorine.

The role of cAMP- and IKK-2-dependent pathways in stimulation of the growth capacity of mesenchymal progenitor cells with alkaloid songorine was studied in vitro. Inhibitors of adenylate cyclase and IKK-2 were shown to abolish the increase in proliferative activity of progenitor cells. Moreover, blockade of the inhibitory kinase complex was accompanied by a decrease in the intensity of progenitor cell differentiation.

Role of receptors to fibroblast growth factor (FGF) on mesenchymal precursor cells in the realization of regenerative effects of alkaloid songorine.

We studied the mechanisms of regenerative (wound healing) effects of songorine associated with functional activation of mesenchymal progenitor cells. The key role of FGF receptors on these progenitor cells in the stimulation of realization of their growth potential under the effect of the alkaloid was demonstrated. Under in vitro conditions, the antibodies to FGF receptor abolished the songorine-induced increase in the number of fibroblast colony-forming units in bone marrow cell culture. The intensity of differentiation of mesenchymal precursors remained unchanged.

Mechanisms of hemostimulating effect of Aconitum baicalense diterpene alkaloids.

A mixture of diterpene alkaloids of Aconitum baicalense exhibited pronounced regenerative hemostimulating properties on the model of cytostatic myelosuppression. The therapeutic effect is based on activation of hemopoietic progenitor cells against the background of increased feeder capacity of stromal compartment of the hemopoiesis-inducing microenvironment and decreased count of mesenchymal stem cells in the bone marrow.

Mechanisms of napelline action stimulating the regeneration of hemopoietic tissue in cytostatic myelosuppression.

Pronounced regenerative effects of alkaloid napelline extracted from Aconitum baicalense on granulocytic hemopoiesis were revealed in the model of cytostatic myelosuppression. Activation of functions of hemopoietic progenitor cells along with increased feeder capacity of the stromal elements in the hemopoiesis inducing microenvironment with decreased levels mesenchymal progenitor cells in the bone marrow are the mechanisms underlying the hemostimulating action of this substance.

[Effect of Scutellaria baicalensis root extract on cytogenetic damage induced by paclitaxel and cisplatin in mice].

The effect of root extract of Baikal skullcap (Scutellaria baicalensis) cultivated in vitro, on the gene structure of CBA/CaLac mice bone marrow cells damaged by anticancer drugs paclitaxel and cisplatin has been studied. It is established that the root extract exhibits gene protective property upon both single and chronic administration.

Mechanisms of regeneratory effects of baikal aconite diterpene alkaloids.

Regeneratory activities of Baikal aconite alkaloids were studied on the excision skin wound model. Manifest wound healing effects of songorine, napelline, and hypaconitine were detected. The therapeutic efficiency was based on activation of residual mesenchymal progenitor elements. The development of this phenomenon was explained by the direct effects of alkaloids on precursors and by higher production of growth factors by the skin stromal cells. Songorine exhibited the most pronounced specific activity due to more significant stimulation of progenitor cell differentiation associated with maximum activation of the secretory function of the microenvironment cells.

[Local mechanisms of the regulatory action of Scutellaria baicalensis and ginseng extracts on the erythropoiesis after paradoxical sleep deprivation].

The influence of ginseng and skullcap (Scutellaria baicalensis) extracts on the local mechanisms of erythropoiesis control under the conditions paradoxical sleep deprivation has been studied. The regulatory action of both preparations on the bone marrow erythropoiesis is based on their ability to influence the proliferation and differentiation in erythroid cells-precursors via modulation of the functional activity of cellular hemopoiesis-inducing microenvironment elements. In particular, the drugs induce changes in the structural and functional organization of the bone marrow and in the production of short-range humoral erythropoiesis regulatory elements.

Neurosis-associated changes in the granulocytic hemopoietic stem in mice with different learning capacity.

We studied the local mechanisms of neurosis-associated changes in the granulocytic hemopoietic stem in CBA/CaLac mice with different learning capacity. It was found that in good learners hyperplasia of the bone marrow granulocytopoiesis during neurosis was related to enhanced proliferative activity and accelerated maturation of granulocyte-macrophage precursors resulting from increased formation of granulocytic and erythrogranulocytic hemopoietic islets. In poor learners primary suppression of the bone marrow granulocytopoiesis was associated with impaired formation of hemopoietic islets (conflict situation) and inhibition of differentiation of granulocyte-macrophage precursors (paradoxical sleep deprivation followed by T-maze learning). Then, recovered ability of bone marrow cells to form granulocyte complexes even against the background of inhibition of precursor differentiation (conflict situation) and accelerated maturation of granulocytic cells (paradoxical sleep deprivation and maze learning) lead to hyperplasia of the granulocytic hemopoietic stem.

Mechanisms of regulation of erythropoiesis during experimental neuroses.

We studied the mechanisms of erythropoiesis regulation in a conflict situation and during paradoxical sleep deprivation. Plastic reconstruction of the erythroid hemopoietic stem during experimental neuroses is regulated by a complex multicomponent and multilevel system. This system consists of central adrenergic structures, sympathetic part of the autonomic nervous system, and alpha- and beta-adrenoceptors on erythroid precursors and cells of the hemopoietic microenvironment. Erythroid cells receive instructive information from the central nervous system via adrenoceptors on cells of the hemopoiesis-inducing microenvironment and erythroid precursors. Hyperplasia (conflict situation) and suppression of erythropoiesis (paradoxical sleep deprivation) are associated with specificity of central adrenergic regulatory mechanisms.

Role of Thy 1,2+ cells in the regulation of hemopoiesis during experimental neuroses.

We studied the direct and stromal cell-mediated effects of bone marrow Thy 1,2+ cells on the growth of granulocyte-macrophage and erythroid colonies from the bone marrow of CBA/CaLac mice with experimental neuroses (conflict situation and paradoxical sleep deprivation). Proliferation and differentiation of hemopoietic precursors during neuroses are controlled by regulatory T cells. In conflict situation Thy 1,2+ cells stimulate the growth of hemopoietic precursors, which is associated with their direct effect and interaction with adherent cells of the hemopoiesis-inducing microenvironment. The interaction of Thy 1,2+ cells with adherent bone marrow cells during paradoxical sleep deprivation stimulates the formation of only granulocyte-macrophage colonies.

Role of stem cells in adaptation to hypoxia and mechanisms of neuroprotective effect of granulocytic colony-stimulating factor.

The role of regional cerebral neural precursor cells in restoration of the CNS activity during the development of hypoxic encephalopathy and the participation of the bone marrow mesenchymal stem cells in the formation of blood system reactions in hypoxia are shown. The mechanisms of neuroprotective effect of granulocytic colony-stimulating factor in severe oxygen insufficiency are studied. The specific psychopharmacological effect of granulocytic colony-stimulating factor is due to mobilization and determined homing of the bone marrow mesenchymal stem cells in damaged CNS zones with subsequent differentiation of these cells into specialized elements and due to activation of erythropoiesis.

Mechanisms of changes in the erythroid hemopoietic stem during hypoxias of different severity.

Brain pathology (acute hypoxia and posthypoxic encephalopathy) is associated with less pronounced hyperplasia of the bone marrow erythroid stem (due to decreased count of proliferating committed precursors) and hemolytic anemia, while secretory activity of stromal cells of the hemopoiesis-inducing microenvironment is not impaired. Severe oxygen deficiency affects erythroid precursors and impairs production of functionally normal erythrocytes in the posthypoxic period.

Mechanisms underling the effects of adaptogens on erythropoiesis during paradoxical sleep deprivation.

We studied the effects of adaptogens extracts of Siberian ginseng, Rhodiola rosea, bergenia, and ginseng and pantohematogen, on erythropoiesis after paradoxical sleep deprivation. Adaptogens stimulated bone marrow erythropoiesis in the early stage, but decreased the count of bone marrow erythrokaryocytes 3-7 days after treatment. The effect of adaptogens on erythropoiesis is associated with modulation of the state of brain neurotransmitter systems followed by changes in functional activity of cells in the hemopoiesis-inducing microenvironment.

Local regulation of proliferation and differentiation of hemopoietic precursors during experimental neuroses.

Intensive formation of hemopoietic islets and secretion of humoral hemopoiesis stimulators by cells of the hemopoietic microenvironment underlie activation of proliferation and differentiation of erythroid and granulocyte-macrophage precursors in conflict situation. Stimulation of division and maturation of committed granulomonocytic precursors during paradoxical sleep deprivation is primarily related to intensive secretion of humoral factors by hemopoietic elements. The inhibition of proliferative activity and differentiation of erythroid precursors is associated with the impaired formation of erythroid hemopoietic islets and suppressed secretion of humoral erythropoiesis stimulators by nonadherent fractions of the hemopoietic microenvironment.

[Hemostimulating properties of cropanol during cytostatics-induced myelosuppression]. / Gemostimuliruiushchie svoistva kropanola pri tsitostaticheskoi mielosupressii.

The granulocyte lineage reaction and its mechanism were studied in the bone marrow of patients with breast cancer in stage III-IV treated according to a specific CAF scheme including cropanol, an antitumor drug of the animal origin. It was found that the bone marrow cytopoiesis suppressed by the cytostatics is stimulated by cropanol on the level of committed precursors, morphologically differentiated bone marrow elements, and peripheral blood.

Reactions of hemopoietic granulocytic stem in hypoxia of different severity.

We studied the reactions of granulocytic hemopoietic stem after acute hypoxia and during the development of posthypoxic encephalopathy. Damage to brain structures was associated with intensification of the bone marrow hemopoiesis due to activation of hemopoiesis-inducing microenvironment and more intense formation of hemopoietic islets, despite reduced proliferative capacity of granulocytic precursors.

Role of the central nervous system in hemopoiesis regulation during experimental neuroses.

Pharmacological blockade of dopamine- and serotoninergic structures with haloperidol and cyproheptadine, respectively, attenuated hyperplasia of bone marrow granulocytopoiesis and erythropoiesis (cyproheptadine) caused by conflict situation. At the same time, haloperidol and, especially, cyproheptadine normalized suppressed erythropoiesis and modulated activated granulocytopoiesis under conditions of paradoxical sleep deprivation. These results indicate that central regulation of hemopoietic stems is mediated by different neurotransmitter mechanisms. Erythropoiesis depends on the state of serotoninergic structures, while granulocytopoiesis is regulated both by the dopamine- and serotoninergic systems.

Mechanisms of myelopoiesis stimulation with pantohematogen and granulocyte colony-stimulating factor during cytostatic myelosuppression.

We compared hemopoiesis-stimulating activities of dry pantohematogen and recombinant granulocyte colony-stimulating factor under conditions of cyclophosphamide-induced myelosuppression. These preparations stimulated regeneration of bone marrow granulomonocytopoiesis by various mechanisms.