T-Lymphocyte proliferative activity in early pregnancy and outside pregnancy state.

T-lymphocytes are present in the endometrium before pregnancy and their number varies depending on menstrual cycle stage. Despite T-lymphocyte population heterogeneity, there is no clear vision of general mechanisms of decidua T-lymphocyte pool formation. One of the assumed variants is T-lymphocyte proliferation in situ. The study objective is to evaluate variations of peripheral blood T-lymphocyte proliferative activity in the presence of trophoblast cells. The peripheral blood was sampled from healthy nonpregnant women in the proliferative (n = 29) and secretory (n = 32) menstrual cycle phases and also from women on 6-7 weeks stage of physiological pregnancy (n = 30). Jeg-3 (ATCC) line cells were applied as trophoblast cells within in vitro model system. T-lymphocyte proliferation was determined by estimating the Ki-67 expression and T-lymphocyte relative number. It was established that trophoblast cells perform inhibiting effect on Ki-67 by T-lymphocytes in all groups of examined women both in course of PBMC cultivation and in case of preliminarily isolated T-lymphocytes. During cultivation in the presence of IL-2 and trophoblasts, PBMC T-lymphocytes in pregnant women are more resistant to trophoblast cells inhibition than in nonpregnant women. In case of isolated T-lymphocytes, decreased T-lymphocyte proliferation during pregnancy was observed as compared to the proliferative cycle phase hence pointing to necessity of T-lymphocyte contact with microenvironment cells for self-support.

NK and trophoblast cells interaction: cytotoxic activity on recurrent pregnancy loss.

The trial objective was to determine the peripheral blood NK cells cytotoxic activity effect on trophoblast cells at recurrent pregnancy loss (RPL). The investigation involved non-pregnant women with PRL in proliferating and secretory menstrual cycle phases (PMCPh and SMCPh, respectively); women of 6-7 weeks pregnancy with RPL in past medical history; healthy fertile non-pregnant women in PMCPh and SMCPh, women of 6-7 weeks physiological pregnancy, nulliparity healthy women with regular menstrual function in PMCPh and SMCPh. NK cells cytotoxic activity was determined using peripheral blood mononuclear cells. The target cells were JEG-3 line trophoblasts. It has been established that NK cells cytotoxic activity effect on trophoblasts is lower in SMCPh than in PMCPh in non-pregnant fertile women. The NK cells cytotoxic activity was higher in SMCPh than in PMCPh in non-pregnant women with PRL and also higher than the same value in SMCPh in non-pregnant fertile women. The increased NK cells cytotoxic activity values in SMCPh in women with RPL may be the reason for miscarriage.

Receptor expression by JEG-3 trophoblast cells in the presence of placenta secreted factors.

Preeclampsia still remains one of the most severe pregnancy complications and is an actual problem in the obstetrics practice. At present, the joint impact of cytokines and other placenta secreted factors on trophoblast cell functional activity during preeclampsia complicated pregnancy remains unclear. The aim of the study is to estimate the surface receptors expression by trophoblast cells in the presence of placenta secreted factors during physiological pregnancy and at preeclampsia. Trophoblast cells of the JEG-3 line were incubated in the presence of supernatants obtained by cultivation of placentas from women with physiological pregnancy and with preeclampsia. Surface receptors expression by trophoblast cells was estimated by FACS Canto II flow cytometer. It was established that in the third trimester both under normal and pathological conditions, the placenta secreted factors impact on the cytokine receptor expression by trophoblast differs while the trophoblast response capacity to the migration and proliferation stimulating and inhibiting signals remains stable. JEG-3 line cells enhanced the expression of CD186, CD140a, Integrin ß6, VE-cadherin, CD29, and CD140a in the case of incubation in the presence of placenta supernatants from the third-trimester pregnancy complicated with preeclampsia compared to incubation in the presence of placenta supernatants form the third trimester of physiological pregnancy.

The effect of solvent relaxation time constants on free energy gap law for ultrafast charge recombination following photoinduced charge separation.

To elucidate the regularities inherent in the kinetics of ultrafast charge recombination following photoinduced charge separation in donor-acceptor dyads in solutions, the simulations of the kinetics have been performed within the stochastic multichannel point-transition model. Increasing the solvent relaxation time scales has been shown to strongly vary the dependence of the charge recombination rate constant on the free energy gap. In slow relaxing solvents the non-equilibrium charge recombination occurring in parallel with solvent relaxation is very effective so that the charge recombination terminates at the non-equilibrium stage. This results in a crucial difference between the free energy gap laws for the ultrafast charge recombination and the thermal charge transfer. For the thermal reactions the well-known Marcus bell-shaped dependence of the rate constant on the free energy gap is realized while for the ultrafast charge recombination only a descending branch is predicted in the whole area of the free energy gap exceeding 0.2 eV. From the available experimental data on the population kinetics of the second and first excited states for a series of Zn-porphyrin-imide dyads in toluene and tetrahydrofuran solutions, an effective rate constant of the charge recombination into the first excited state has been calculated. The obtained rate constant being very high is nearly invariable in the area of the charge recombination free energy gap from 0.2 to 0.6 eV that supports the theoretical prediction.

Verification of Nonequilibrium Mechanism of Ultrafast Charge Recombination in Excited Donor-Acceptor Complexes.

Control of charge transfer requires knowledge of its detailed mechanism. Due to the large number of known mechanisms, the identification of the mechanism in specific systems is a challenge so far. In this article we propose the idea of how to distinguish between thermal and nonequilibrium modes of charge recombination in excited donor-acceptor complexes. Simulations of the effect of solvent relaxation time scale on ultrafast charge recombination kinetics in photoexcited donor-acceptor complexes within the framework of the multichannel stochastic model have shown that a series of regularities inherent to the thermal and nonequilibrium charge transfer can strongly differ. Among them there are opposite regularities, for example, the dependence of the dynamic solvent effect on the free energy gap. In particular, theory predicts that in ultrafast charge recombination of excited donor-acceptor complexes the dynamic solvent effect is weak in the area of weak exergonicity and becomes stronger in the area of stronger exergonicity whereas for the thermal reactions an opposite trend is expected. Comparison of such trends with experimental data implemented in this article allowed establishing the regime in which the reaction proceeds. It is shown that observation of dynamic solvent effect in the region of strong exergonicity for ultrafast charge recombination is decisive evidence in favor of nonequilibrium mechanism.

Dynamic Solvent Effect on Ultrafast Charge Recombination Kinetics in Excited Donor-Acceptor Complexes.

Manifestation of the dynamic solvent effect (DSE) on the charge recombination (CR) kinetics of photoexcited donor-acceptor complexes in polar solvents has been investigated within the framework of the multichannel stochastic model. The model takes into account the reorganization of both the solvent and a number of intramolecular high-frequency vibration modes as well as their relaxation. The non-Markovian solvent dynamics is described in terms of two relaxation modes. The similarities and differences inherent to ultrafast charge transfer reactions occurring in the nonequilibrium and thermal regimes have been identified. The most important differences are as follows: (1) the DSE is strong in the area of weak exergonicity and is weak in the area of strong exergonicity for thermal reactions, whereas for the nonequilibrium reactions, the regions of strong and weak DSEs are reversed; (2) an increase in the electronic coupling value results in a decrease in the magnitude of DSE for nonequilibrium electron transfer and in its increase for the thermal reactions; and (3) the two-staged regime most clearly manifests if the reorganization energy of the relaxation modes noticeably exceeds the CR free-energy gap. With an increase in electronic coupling, the kinetics approaches the exponential regime because in the limit of strong electronic coupling, the reaction includes only single, nonequilibrium, stage.

Reorganization of intramolecular high frequency vibrational modes and dynamic solvent effect in electron transfer reactions.

The possibility of the multichannel stochastic model to adequately describe all principal regularities observed in thermal electron transfer kinetics has been demonstrated. The most important are as follows: (i) the model predicts the solvent controlled regime in the Marcus normal region and its almost full suppression in the Marcus inverted region as well as a continuous transition between them in the vicinity of the activationless region; (ii) the suppression of dynamic solvent effect (DSE) is principally caused by the reorganization of high frequency vibrational modes; (iii) an additional factor of the DSE suppression stems from fast solvent relaxation component; (iv) in the inverted region, the multichannel stochastic model predicts the apparent activation energy to be much less than that calculated with Marcus equation. The exploration of the multichannel stochastic model has allowed one to conclude that the reorganization of high frequency vibrational modes can (i) raise the maximum rate constant above the solvent controlled limit by 2 and more orders of magnitude, (ii) shift the rate constant maximum to larger values of the free energy gap, and (iii) approach the electron transfer kinetics to the nonadiabatic regime.

Nonequilibrium phenomena in charge recombination of excited donor-acceptor complexes and free energy gap law.

The charge recombination dynamics of excited donor-acceptor complexes in polar solvents has been investigated within the framework of the stochastic approach. The model involves the excited state formation by the pump pulse and accounts for the reorganization of a number of intramolecular high-frequency vibrational modes, for their relaxation as well as for the solvent reorganization following nonexponential relaxation. The hot transitions accelerate the charge recombination in the low exergonic region and suppress it in the region of moderate exothermicity. This straightens the dependence of the logarithm of the charge recombination rate constant on the free energy gap to the form that can be fitted to the experimental data. The free energy dependence of the charge recombination rate constant can be well fitted to the multichannel stochastic model if the donor-acceptor complexes are separated into a few groups with different values of the electronic coupling. The model provides correct description of the nonexponential charge recombination dynamics in excited donor-acceptor complexes, in particular, nearly exponential recombination in perylene-tetracyanoethylene complex in acetonitrile. It appears that majority of the initially excited donor-acceptor complexes recombines in a nonthermal (hot) stage when the nonequilibrium wave packet passes through a number of term crossings corresponding to transitions toward vibrational excited states of the electronic ground state in the area of the low and moderate exothermicity.

Three-centered model of ultrafast photoinduced charge transfer: continuum dielectric approach.

A theoretical description of photoinduced charge transfer involves explicit treating both the optical formation of the nuclear wave packet on the excited free energy surface and its ensuing dynamics. The reaction pathway constitutes two-stage charge transfer between three centers. Manifestations of fractional charge transfer at first stage are explored. An expression for time dependent rate constant of photoinduced charge transfer is found in the framework of the linear dielectric continuum model of the medium. The model involves both the intramolecular vibrational reorganization and the Coulombic interaction of the transferred charge with the medium polarization fluctuations and allows to express the rate in terms of intramolecular reorganization parameters and complex dielectric permittivity. The influence of the vibrational coherent motion in the locally excited state on the charge transfer dynamics has been explored. The dependence of the ultrafast photoinduced charge transfer dynamics on the excitation pulse carrier frequency (spectral effect) has been investigated. The spectral effect has been shown to depend on quantity of the fractional charge.

Nonequilibrium charge recombination from the excited adiabatic state of donor-acceptor complexes.

A model of nonequilibrium charge recombination from an excited adiabatic state of a donor-acceptor complex induced by the nonadiabatic interaction operator is considered. The decay of the excited state population prepared by a short laser pulse is shown to be highly nonexponential. The influence of the excitation pulse carrier frequency on the ultrafast charge recombination dynamics of excited donor-acceptor complexes is explored. The charge recombination rate constant is found to decrease with increasing excitation frequency. The variation of the excitation pulse carrier frequency within the charge transfer absorption band of the complex can alter the effective charge recombination rate by up to a factor 2. The magnitude of this spectral effect decreases strongly with increasing electronic coupling.