The Role of Hydroxyeicosatetraenoic Acids in the Regulation of Inflammation in Bronchial Asthma.

Hydroperoxyeicosatetraenoic acids (HETEs) are metabolites of arachidonic acid that are oxidized by a family of enzymes including cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes. These enzymes are widely present in various organs and tissues, and the HETEs they synthesize perform an important function in the regulation of immune reactions and haemostasis processes under physiological and pathophysiological conditions. More researchers confirm the role of these oxidized metabolites in modulating inflammation in asthma. The high production of HETEs in allergic and severe asthma indicates their involvement in the processes of an acute inflammatory response. On the other hand, disturbance of the metabolic transformation of arachidonic acid contributes to the development of chronic inflammation due to insufficient synthesis of mediators that resolve inflammatory processes. Several HETEs have both pro-inflammatory and anti-inflammatory effects, which underscores the ongoing interest in their involvement in the pathogenesis of asthma. At the same time, research results are scarce. Based on an analysis of the literature, the pathways of metabolic transformation of 5-HETE, 12-HETE, and 15-HETE with the participation of cyclooxygenases, lipoxygenases, and cytochrome P-450, as well as their role in asthma pathogenesis, were discussed. The PubMed database was searched for information covering the last five years using selected inclusion criteria. Information queries included the following set of keywords: "bronchial asthma, hydroxyeicosatetraenoic acids, 5-HETE, 12-HETE, 15-HETE." Literature data indicate that the role of HETEs in human physiology and pathology, including the modulation of inflammation in asthma, requires comprehensive study to selectively modulate the enzymatic pathways of arachidonic acid metabolism leading to the production of these mediators.

Temporal evolution of bacterial species and their antimicrobial resistance characteristics in wound infections of war-related injuries in Ukraine from 2014 to 2023.

BACKGROUND: This study continues surveillance of antimicrobial resistance associated with combat injuries in Ukraine. AIM: To compare species composition, antibiotic resistance profiles, and emergence of new resistance genes between 2014-2020 and 2022-2023. METHODS: This was a retrospective multi-centre microbiological survey in Ukrainian hospitals. Antibiotic susceptibility, whole-genome sequencing and multi-locus sequence typing were conducted on 154 organisms obtained from 125 casualties between 2022 and 2023. FINDINGS: The data revealed a predominance of Gram-negative bacteria, particularly Acinetobacter baumannii (35.7%), Pseudomonas aeruginosa (14.9%) and Klebsiella pneumoniae (20.7%). High levels of carbapenem resistance were observed among A. baumannii {meropenem 72.2% [39/54, 95% confidence interval (CI) 58.4-83.5]; imipenem 66.7% (36/54, 95% CI 52.5-78.9)}, K. pneumoniae [meropenem 90.6% (29/32, 95% CI 75.0-98.0); imipenem 81.2% (26/32, 95% CI 63.6-92.8)] and P. aeruginosa [meropenem 47.8% (11/23, 95% CI 26.8-69.4); imipenem 60.8% (14/23, 95% CI 38.5-80.3)] strains. A. baumannii sequence type (ST)-78 and ST-400 were prevalent from 2014 to 2020, while five strains of ST-1077 were newly identified in 2022-2023. P. aeruginosa strains showed diversity across 16 STs, with ST-773 increasing in frequency and new STs emerging, but lacking carbapenemase genes. K. pneumoniae exhibited increased genetic diversity over time, with three STs from 2014 to 2020 and six new STs, including blaNDM-1, blaOXA-48 and blaKPC2 carriers, in 2022-2023. CONCLUSION: The prevalence of multi-drug-resistant isolates with STs associated with a high risk of global dissemination is increasing.

Correlations of Expression Levels of Lung Cancer Marker Gene Eno2 and Genes of Carcinogenesis and Apoptosis in the Hypothalamus of Mice with Depression-Like Behavior.

We experimentally demonstrated that chronic social stress during the development of a depression-like state enhances lung metastasis and modifies the expression of many carcinogenesis- and apoptosis-related genes in the hypothalamus of mice, including genes involved in lung cancer pathogenesis in humans. Analysis of the expression of genes encoding the major clinical markers of lung cancer in the hypothalamus of mice with depression-like behavior revealed increased expression of the Eno2 gene encoding neuron-specific enolase, a blood marker of lung cancer progression in humans. It was shown that the expression of this gene in the hypothalamus correlated with the expression of many carcinogenesis- and apoptosis-related genes. The discovered phenomenon may have a fundamental significance and requires further studies.

Theory-based cryopreservation mode of mesenchymal stromal cell spheroids.

Cryopreservation of spheroids requires development of new improved methods. The plasma membranes permeability coefficients for water and cryoprotectants determine time characteristics of mass transfer through the cell membranes, and therefore the optimal modes of cells cryopreservation. Here we proposed an approach to cryopreservation of multicellular spheroids which considers their generalized characteristics as analogues of the membranes' permeability coefficients of the individual cells. We have determined such integral characteristics of spheroids from mesenchymal stromal cells (MSCs) as osmotically inactive volume; permeability coefficients for water and Me2SO molecules and the activation energy of their penetration. Based on these characteristics, we calculated the osmotic behavior of multicellular spheroids under cooling conditions to select the optimal cooling rate. We also determined the optimal cooling rate of spheroids using the probabilistic model developed based on the two-factor theory of cryodamage. From the calculation it follows that the optimal cooling rate of the MSC-based spheroids is 0.75°Ð¡/min. To verify the obtained theoretical estimates, we conducted experiments on freezing MSC-based spheroids under different modes. The obtained results of primary viability screening indicate that freezing at a constant linear cooling rate of 0.75-1.0°Ð¡/min gives a good result. Theoretical prediction of the spheroid osmotic behavior during cooling provided the basis for experimental verification of varying the temperature to which slow cooling should be carried out before immersion in liquid nitrogen. Slow freezing of spheroids to -40 °C followed by immersion in liquid nitrogen was shown to preserve cells better than slow freezing to -80 °C. Obtained data allow more effective use of MSC-based spheroids in drug screening and regenerative medicine.

Factors influencing the increased 90Sr radioisotope migration in highly alkaline groundwater at Chornobyl NPP site.

This paper analyses the formation of high Sr2+ concentration in strong alkaline (pH = 9.5-12.5) groundwater using data of the 27 years of observations around the destroyed Chernobyl NPP Unit 4. It appears that the formation of strong alkaline groundwater in different monitoring wells is consistent with the distribution of 90Sr, pH and main ions. The reason for the increase in 90Sr concentrations is the process of its migration from the sources of contamination - leaks of highly active water localized in certain premises inside the «Shelter ¼ object. These computational experiments showed that for the groundwater in pH range 9.5-12.4, the concentration of strontium in the form of SrOH + increases and in the form of Sr2+ - decreases. In addition, the fraction of 90Sr in the form of a soluble neutral complex compound SrCO30, which is not sorbed, reaches 14-35%. Increased fractions of 90Sr in forms of SrOH+ and SrCO3 are factors which reduce the isotope ability to be sorbed by soils and therefore increase its migration ability. In strongly alkaline groundwater a sharp increase in 90Sr volumetric activity may also be caused by ionic strength (IS) increase above 5 mmol/L. Thus, the factors that influence the increase in 90Sr volumetric activity in strongly alkaline groundwater are the formation of its complex compounds and an increase in ionic strength (IS), which reduces the thickness of the double electric layer and, as a result, reduces the sorption capacity of soils.

Determination of cell membrane permeability coefficients: Comparison of models in the case of oocytes.

Values of cell membranes permeability coefficients for water and molecules of cryoprotective agents (CPAs) are the necessary characteristics for developing physical-mathematical models describing mass transfer processes through cell membranes in order to predict optimal cell cooling rates. We carried out a comparative analysis of the permeability coefficients of mouse oocyte membranes for molecules of water, ethylene glycol (EG), propane-1,2-diol (1,2-PD) and dimethyl sulfoxide (Me2SO), determined by applying the classical Kedem-Katchalsky model, which considers only the penetration of non-electrolyte molecules (water and CPA) through the membrane, and the model developed by us, which takes into account the transmembrane transfer of ions and the associated changes in the transmembrane electric potential. We shown that calculations based on the developed modified model provide lower values of the permeability coefficients of the oocyte membrane for water and CPA molecules. What is important that the obtained by our modified model permeability coefficients for water molecules do not depend on the type of cryoprotectant, while the application of the classical model both in our studies and works of other authors always gave different values of these coefficients in solutions with different cryoprotectants. Our modified model also makes it possible to determine the dynamics of the transmembrane electric potential of the cell under the conditions of transmembrane mass transfer and the duration of the membrane being influenced by the changes in electric potential, that is a parameter that can directly affect the viability of cells.

Isotope composition of groundwater and surface waters in the area of the Dombrovsky quarry of Kalush-Golinsk deposit of potassium salts.

Enrichment of heavy isotopes of hydrogen (D, 3H) and oxygen (18О) is observed in water samples collected from open brine storage of Kalush-Golinsky deposit. The brine storage facilities were formed during the operation of the Kalush-Golynsky deposit of potassium salts and after its decommissioning. Enrichment of isotopes is also observed in groundwater samples, collected from wells located along with downstream groundwater from brine storage facilities. The analysis of levels of influence of possible sources of chemical pollution of groundwater (waters of the Dombrovsky quarry, tailings and sludge storage, salt dumps, saline soils) and correlation relationships between isotopes and groundwater mineralization have been determined by statistical processing of geochemical data.

Possibilities of Endovascular Hemostasis in Treatment of Pancreatic Bleeding.

Pancreatic hemorrhage is one of the most severe complications of various pancreatic diseases that are difficult to treat even in multidisciplinary hospitals. Mortality from pancreatic hemorrhage can reach up to 80%. This study aimed to evaluate the possibility of maintaining endovascular homeostasis in the treatment of patients with pancreatic hemorrhage. This retrospective multicenter study included 45 patients (33 men and 12 women) in the age range of 27-84 years. More than 50% (n=23) of the patients were diagnosed with chronic pancreatitis. Malignant pancreatic lesions were observed in 22 patients; of whom11 patients had acute necrotizing pancreatitis. Acute bleeding was observed in 39 (86.6%) patients, and 6 (13.3%) patients showed chronic symptoms. Single-shot and recurrent bleeding was recorded in 22(48.9%) and 23 (51.1%) patients. In total, 57 patients underwent endovascular surgery. Moreover, 45 patients underwent primary surgery and another 12 (2.2%) underwent reoperation due to recurrent bleeding. Intraoperative complications occurred in 1 (2.2%) patient, and postoperative complications occurred in another. Out of all 45 patients, seven patients had 15 episodes of recurrent bleeding, of whom four patients showed recurrent bleeding at the in-hospital period, and the other three were under local supervision after the previous endovascular intervention. Out of the 45 patients, 35 (77.7%) survived and another 10 (22.2%) died due to multiple organ failure (n=8) and recurrent bleeding and hemorrhagic shock (n=2). Out of 10 patients who died, 4, 3, and 3patients showed malignant pancreatic lesions after surgery, acute pancreatitis, and chronic pancreatitis, respectively. Endovascular hemostatic interventions can significantly increase the survival rate in severe groups of patients with pancreatic bleeding. Endovascular hemostasis is a safe procedure and may be called the "method of choice" in the treatment of pancreatic bleeding, especially in combination with percutaneous draining, aspiration, and injection of liquid embolic agents into leakage of pancreatic juice.

[Fatty acid epoxides in the regulation of the inflammation]. / Époksidy polinenasyshchennykh zhirnykh kislot v reguliatsii vospaleniia.

Cyclooxygenase and lipoxygenase derived lipid metabolites of polyunsaturated fatty acids (PUFAs), as well as their role in the inflammation, have been studied quite thoroughly. However, cytochrome P450 derived lipid mediators, as well as their participation in the regulation of the inflammation, need deeper understanding. In recent years, it has become known that PUFAs are oxidized by cytochrome P450 epoxygenases to epoxy fatty acids, which act as the extremely powerful lipid mediators involved in resolving inflammation. Recent studies have shown that the anti-inflammatory mechanisms of ω-3 PUFAs are also mediated by their conversion to the endocannabinoid epoxides. Thus, it is clear that a number of therapeutically relevant functions of PUFAs are due to their conversion to PUFA epoxides. However, with the participation of cytochrome P450 epoxygenases, not only PUFA epoxides, but also other metabolites are formed. They are further are converted by epoxide hydrolases into pro-inflammatory dihydroxy fatty acids and anti-inflammatory dihydroxyeicosatrienoic acids. The study of the role of PUFA epoxides in the regulation of the inflammation and pharmacological modeling of the activity of epoxide hydrolases are the promising strategies for the treatment of the inflammatory diseases. This review systematizes the current literature data of the fatty acid epoxides, in particular, the endocannabinoid epoxides. Their role in the regulation of inflammation is discussed.

Tofacitinib for the treatment of refractory pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a rare, debilitating, inflammatory skin disease associated with a variety of systemic diseases. Because of its rarity, PG is treated with miscellaneous immunosuppressive agents as there is no US Food and Drug Administration-approved standardized treatment approach. We present four patients with PG treated with tofacitinib in the context of the six existing cases in the literature. Tofacitinib appeared to be beneficial in the small sample of patients (n = 10) who failed an average of four other systemic therapies. The majority of patients had classic PG located on the legs (80%, 8/10), while 20% of cases (2/10) were peristomal. The most common comorbidity was inflammatory bowel disease (78%, 7/9). There were no negative treatment results and 40% (4/10) of patients had complete healing of their ulcers, while the other 60% (6/10) had marked clinical improvement. From our observation, tofacitinib appears to be a promising steroid-sparing adjuvant treatment in patients with refractory PG who have failed on other systemic therapies.

Phenotypic and genotypic characterization of antibiotic resistance in military hospital-associated bacteria from war injuries in the Eastern Ukraine conflict between 2014 and 2020.

BACKGROUND: Infections from the recent conflict in Ukraine have been poorly investigated. AIM: To describe the phenotypic and genotypic mechanisms of antibiotic resistance in pathogens associated with war injuries in the Ukraine conflict. METHODS: This report describes a retrospective multi-centre microbiological survey conducted in four Ukrainian military hospitals between 2014 and 2020. The phenotypes of 813 organisms obtained from 1061 tests of 162 patients were analysed. Fifty-two isolates underwent whole-genome sequencing. FINDINGS: Resistance was highest in Acinetobacter baumannii, with 92.5% ((48/52) 95% confidence interval (CI) 81.8-97.9) resistant to fluoroquinolones, 83.0% ((43/52) 95% CI 70.2-91.9) resistant to aminoglycosides, and 67.9% ((37/52) 95% CI 53.7-80.1) resistant to carbapenems. In contrast, resistance to carbapenems was 55.6% ((30/52) 95% CI 41.4-69.1) in Pseudomonas aeruginosa, 42.9% in Escherichia coli ((12/28) 95% CI 24.5-62.8), and 32.8% in Klebsiella pneumoniae ((20/34) 95% CI 21.3-46.0). Multi-drug-resistant strains harboured an abundance of antibiotic resistance genes. K. pneumoniae co-produced class A and D ß-lactamases, in one case with blaNDM-1 and rmtC 16S rRNA methyltransferase. A. baumannii carried class A and D ß-lactamases but not metallo-ß-lactamases; in four isolates, carbapenemases were present with the RmtASE gene armA. P. aeruginosa harboured a wide range of class A and D ß-lactamases along with metallo-ß-lactamases, as well as the RmtB4 RmtASE gene. Gram-positive cocci were generally sensitive to the tested antibiotics. CONCLUSION: The incidence of resistance among the studied pathogens was higher than that in Ukrainian civilian hospitals and European countries. The discovery of P. aeruginosa, A. baumannii, and K. pneumoniae co-producing carbapenemases and RmtASEs is of particular importance, and hospitals should be vigilant for their emergence.

Cationic Antiseptics Facilitate Pore Formation in Model Bacterial Membranes.

Antiseptics are an essential line of defense against bacterial and viral infections in modern medical practice. Many of them are supposed to act on microbial membranes. However, the detailed mechanisms of their action are still elusive. Here, we utilized coarse-grained molecular dynamics simulations to investigate interactions of different types of cationic antiseptics (CAs) with a model bacterial membrane. The simulations revealed qualitatively distinct patterns of dynamic and structural alterations of membrane induced by different types of antiseptics although none of them caused disintegration or solubilization of the bilayer even at the highest explored concentration. At the same time, the adsorption of antiseptics rendered membranes more vulnerable to poration under exposure to the external electric field. We further discuss the possible relation of the enhanced pore formation induced by CAs to their cytotoxic action.

[The remote results of treatment of ischemic stroke conditioned by atherosclerotic affection of carotid arteries].

The ischemic stroke is a disease that leads to dysfunctions in life of any individual. The mortality rate of cerebral infarcts reaches up to 39%. Besides, the most acute period of an ischemic stroke, which lasts up to 5-7 days, is especially problematic and is characterized by the highest mortality. The first day of disease results in 21.74% of deaths (out of the total annual number of deaths). The article presents the results of the analysis of treatment of the patients with ischemic stroke caused by the atherosclerosis of brachiocephalic arteries. The role of endovascular technologies in the treatment of the acute cerebrovascular cases has not been fully revealed. The retrospective analysis of treatment of 171 patients with atherosclerotic subtype of ischemic stroke was carried out. The patients were distributed in two groups: in the first group (83 patients) the applied conservative therapy was supplemented by endovascular intervention during the acute period of ischemic insult; in the second group (88 patients) the conservative therapy alone was applied. Both groups were comparable in terms of gender, age and associated diseases. The risk factors of ischemic insult were analyzed such as IHD that requires surgery; hypertensive disease; hypercholesterolemia; ischemic insult in medical history; heart dysrhythmia; diabetes mellitus. All patients had more than one risk factor. There mortality, incapacitation, degree of neurological impairment, frequency of symptoms of hemorrhagic suffusion and of hemorrhagic transformation were analyzed. The remote results were analyzed in sampling of 54 patients: 32 patients from the first group, 22 patients from the second group. The quality of life was measured using technique of non-specific survey SF-36 when its 36 items were grouped into eight scales: physical functioning, role activity, body pain, general health, vitality, social functioning, emotional state, psychological health. The degree of incapacitation was measured with the modified Rankin scale, the quality of life was examined with the SF-36 survey, the survival rate was measured with the Kaplan-Meier estimator. The statistical analysis was carried out with the help of the Statistica 6.0 software.

Theoretical Estimation of the Optimum Cooling Rate of a Cell Suspension at Linear Freezing Modes Based on a Two Factor Theory of Cryodamage.

BACKGROUND: According to the two-factor theory cryodamage arises from intracellular crystallization and solution effects due to freeze concentration. OBJECTIVE: The study aims to evaluate the contribution of two types of cryodamages that are related to extra- and intracellular crystallization. METHODS: The probability of intracellular crystal formation during cooling of cell suspension in cryoprotective solution has been determined based on general thermodynamics theory. RESULTS: According to the obtained correlations and taking into account of the individual characteristics of yeast cells and murine enterocytes, the optimal cooling rates during freezing of these cells in cryoprotectant solutions were determined. CONCLUSION: The proposed algorithm for the estimation of the optimal cooling rates at linear freezing mode of a particular cellular suspension can be utilized to develope methods for cryopreservation of different cell suspensions.

[Serotonergic genes in the development of anxiety/depression-like state and pathology of aggressive behavior in male mice: RNA-seq data].

In course of daily agonistic interactions, mice tend to stratify into those with chronic social defeats and those that repeatedly display aggression, which lead to the development of mixed anxiety/depression-like state and the pathology of aggressive behavior, respectively. Using the data of whole transcriptome analysis (RNA-seq), the changes in the expression of serotonergic genes involved in the synthesis, inactivation, and reception of serotonin, as well as of the Creb1 (transcription factor) gene and the Bdnf (brain-derived neurotrophic factor) gene were detected in the striatum (STR), ventral tegmental area (VTA), midbrain raphe nuclei (MRN), hypothalamus (HYP), and hippocampus (HIP) of defeated and aggressive male mice. In mice of both groups, the Tph2, Ddc, Slc6a4, Htr2a, Htr3a, Htr5b, Slc18a2, and Bdnf genes were downregulated in the MRN and the Tph2, Ddc, and Slc6a4 genes were upregulated in the VTA. These changes were more significant in defeated mice. The Htr5b gene has first been shown to be involved in mechanisms of depression and pathology of aggressive behavior. In the defeated mice, the expression levels of the Htr4 and Aldh1b1 genes were increased in the MRN, and expression levels of the Maob, Htr4, Htr1a, and Slc18a2 genes were increased in the VTA, while the expression level of the Htr3a gene was decreased. In the HYP of aggressive mice the Maoa, Htr2a, Htr2c, and Creb1 genes were downregulated and the Htr6 gene was upregulated. In the defeated mice, the Maoa and Creb1 genes were downregulated and the Htr6 and Aldh1b1 genes were upregulated in the HYP. In the STR, the Htr1a gene was downregulated and the Htr7 and Bdnf genes were upregulated. The Htr1b gene was upregulated in the HIP. The coexpression of dopaminergic and serotonergic genes in the MRN and VTA in the control of pathological behaviors is discussed. Thus, the complex pattern of differential expression of serotonergic genes in brain regions developing under repeated agonistic interactions in mice in dependence on behavioral pathology have been observed.

[Altered Expression of Neurotransmitters Systems' Genes in the Ventral Tegmental Area of Depressive Male Mice: Data of RNA-Seq].

Chronic social defeat stress (CSDS) leads to the development of mixed anxiety/depression-like state in male mice similar to those in humans. It has been shown that, under CSDS, the adult brain undergoes changes in the functioning neurotransmitter systems in different brain regions. In this experiment we are focused on the analysis of expression of genes encoding proteins related with the metabolism and receptors of serotonin, catecholamines, GABA and glutamate in the ventral teg- mental area which is important for regulation of motivations, emotions and is involved into mech- anisms of affective disorders. Mixed anxiety/depression-like state was generated in male mice by exposure to CSDS during 20 days. The collected samples of the ventral tegmental area were se-- quenced at JSC Genoanalytica,(http://genoanalytica.ru/, Moscow, Russia).'We found that genes, related with serotonin (Tph2, Maob, SIc6a4, Htr4, Htr1a) were upregulated but expression of Htr3a gene was downregulated in the ventral tegmental area of depressive mice in comparison with the control. Besides, upregulation of dopaminergic Th, Ddc, Slc6a3, Sic18a2, Drd2, and Maob genes was found while noradrenergic Dbh, Slc6a2, Adra2c, and Adra2a genes were downregulated. Ex- pression of GABAergic Gabral, Gabra2, Gabrg2, Gabrg], Gabrq, Gad], and Gad genes as well as glutamatergic Grial, Gria2, Grik2, Grm2, Grm5, and Slc 7a8 genes were increased under CSDS. Development of mixed anxiety/depression-like state under CSDS in male mice is accompanied by increased expression of genes coding the proteins participating in the metabolism and receptions of serotonergic, dopaminergic, glutamatergic and GABAergic systems. Expression of genes coding the adrenergic reception is decreased. It is supposed that Drd2 H Htr3a genes may play the key role in the synchronization of other genes of neurotransmitter systems.

Influence of pH and ionic strength on electrostatic properties of ferredoxin, FNR, and hydrogenase and the rate constants of their interaction.

Ferredoxin (Fd) protein transfers electrons from photosystem I (PSI) to ferredoxin:NADP+-reductase (FNR) in the photosynthetic electron transport chain, as well as other metabolic pathways. In some photosynthetic organisms including cyanobacteria and green unicellular algae under anaerobic conditions Fd transfers electrons not only to FNR but also to hydrogenase-an enzyme which catalyzes reduction of atomic hydrogen to H2. One of the questions posed by this competitive relationship between proteins is which characteristics of thylakoid stroma media allow switching of the electron flow between the linear path PSI-Fd-FNR-NADP+ and the path PSI-Fd-hydrogenase-H2. The study was conducted using direct multiparticle simulation approach. In this method protein molecules are considered as individual objects that experience Brownian motion and electrostatic interaction with the surrounding media and each other. Using the model we studied the effects of pH and ionic strength (I) upon complex formation between ferredoxin and FNR and ferredoxin and hydrogenase. We showed that the rate constant of Fd-FNR complex formation is constant in a wide range of physiologically significant pH values. Therefore it can be argued that regulation of FNR activity doesn't involve pH changes in stroma. On the other hand, in the model rate constant of Fd-hydrogenase interaction dramatically depends upon pH: in the range 7-9 it increases threefold. It may seem that because hydrogenase reduces protons it should be more active when pH is acidic. Apparently, regulation of hydrogenase's affinity to both her reaction partners (H+ and Fd) is carried out by changes in its electrostatic properties. In the dark, the protein is inactive and in the light it is activated and starts to interact with both Fd and H+. Therefore, we can conclude that in chloroplasts the rate of hydrogen production is regulated by pH through the changes in the affinity between hydrogenase and ferredoxin.

Serum Levels of 8-Hydroxy-2'-Deoxyguanosine DNA in Patients with Breast Cancer and Endometrial Cancer with and without Diabetes Mellitus.

Blood levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured by enzyme immunoassay after overnight fasting in untreated breast cancer and endometrial cancer patients (N=170) of mainly postmenopausal age with and without type 2 diabetes mellitus. The concentrations of 8-OHdG in patients with breast cancer were higher than in patients with endometrial cancer and in patients with breast cancer and diabetes in comparison with patients with breast cancer without diabetes. No correlations of blood 8-OHdG levels with glycemia, age, and clinical stage of disease were detected. In cancer patients with diabetes, the concentration of 8-OHdG increases proportionally to the increase in body mass index, though this does not lead to disappearance of the above differences between patients with breast cancer and endometrial cancer by the level of 8-OHdG. The causes of the trend to a less favorable course of tumor process in patients with breast cancer and diabetes in comparison with endometrial cancer and diabetes deserve further studies.

[Relationship of Anxiety and Depression in the Development of Mixed Anxiety/Depression Disorder. An Experimental Study of Comorbidity Mechanisms (Review)].

As clinical practice and experimental studies show, symptoms of depression and anxiety often accompany each other. It is well known that combination of anxiety and depression in patients is treated more slowly, requires large doses of drugs, increases the likelihood of suicide and often leads to relapse. Furthermore, antidepressants and anxiolytics exert its therapeutic effect in limited cases even in monopolar anxiety or depression state. In this review of literature and our own data the relationship of anxiety and depression is analyzed. It has been shown with using the model of mixed anxiety/depression disorder caused by chronic social defeat stress, that the anxiety and depression are changed under the influence of psychotropic drugs independently.

The role of electrostatic interactions in the process of diffusional encounter and docking of electron transport proteins.

Electrostatic interaction of plastocyanin and cytochrome f in the process of protein-protein complex formation was investigated by computer simulation methods. It was shown that long-range electrostatic interaction promotes energetically favorable mutual orientation of protein molecules at distances between their cofactors shorter than 5 nm. At distances shorter than 3 nm, these electrostatic interactions lead to a significantly detectable increase in the rate of convergence of the cofactors.