Biomeditsinskaia Khimiia[JOURNAL]
Sun
200 papers
The search for potential hypotensive peptides in the amino acid sequence of human renalase and their identification in proteolytic fragments of this protein.
Fedchenko VI, Veselovsky AV, Kopylov AT … +1 more , Medvedev AE
Biomed Khim · 2023 Dec · PMID 38153055 · Publisher ↗
Renalase (RNLS) is a secretory protein discovered in 2005. It plays an important role in the regulation of blood pressure. Studies by two independent laboratories have shown that administration of purified recombinant RN...
Renalase (RNLS) is a secretory protein discovered in 2005. It plays an important role in the regulation of blood pressure. Studies by two independent laboratories have shown that administration of purified recombinant RNLS reduced blood pressure in experimental animals. However, the mechanisms of the antihypertensive effect of RNLS still remain unclear, especially in the context of the shift in the catalytic paradigm of this protein. In addition, there is growing evidence that endogenous plasma/serum RNLS, detected by enzyme immunoassay, is not an intact protein secreted into the extracellular space, and exogenous recombinant RNLS is effectively cleaved during short-term incubation with human plasma samples. This suggests that the antihypertensive effect of RNLS may be due to peptides formed during proteolytic processing. Based on the results of a bioinformatics analysis of potential RNLS cleavage sites (Fedchenko et al., Medical Hypotheses, 2022; DOI: 10.1016/j.mehy.2022.110895), a number of short peptides have been identified in the RNLS sequence that show similarity to fragments of known peptide inhibitors of angiotensin-converting enzyme. Some of them were found as a part of larger RNLS peptides, formed during RNLS cleavage by chymotrypsin and, and to a lesser extent, by trypsin.
The effect of hyperglycemia on the activation of peritoneal macrophages of albino rats.
Golyako IA, Kuzmin VS, Gorbacheva LR
Biomed Khim · 2023 Dec · PMID 38153054 · Publisher ↗
Hyperglycemia is one of the main damaging factors of diabetes mellitus (DM). The severity of this disease is most clearly manifested under conditions of the inflammatory process. In this work, we have studied the activat...
Hyperglycemia is one of the main damaging factors of diabetes mellitus (DM). The severity of this disease is most clearly manifested under conditions of the inflammatory process. In this work, we have studied the activation features of rat peritoneal macrophages (MPs) under conditions of high glucose concentration in vitro. Comparison of the independent and combined effects of streptozotocin-induced DM and hyperglycemia on proliferation and accumulation of nitrites in the MPs culture medium revealed similarity of their effects. Elevated glucose levels and, to a lesser extent, DM decreased basal proliferation and NO production by MPs in vitro. The use of the protein kinase C (PKC) activator, phorbol ester (PMA), abolished the proinflammatory effect of thrombin on PMs. This suggests the involvement of PKC in the effects of the protease. At the same time, the effect of thrombin on the level of nitrites in the culture medium demonstrates a pronounced dose-dependence, which was not recognized during evaluation of proliferation. Proinflammatory activation of MPs is potentiated by hyperglycemia, one of the main pathological factors of diabetes. Despite the fact that high concentrations of glucose have a significant effect on proliferation and NO production, no statistically significant differences were found between the responses of MPs obtained from healthy animals and from animals with streptozotocin-induced DM. This ratio was observed for all parameters studied in the work, during analysis of cell proliferation and measurement of nitrites in the culture medium. Thus, the results obtained indicate the leading role of elevated glucose levels in the regulation of MPs activation, which is comparable to the effect of DM and even "masks" it.
System analysis of surface CD markers during the process of granulocytic differentiation.
Novikova SE, Tolstova TV, Soloveva NA … +5 more , Farafonova TE, Tikhonova OV, Kurbatov LK, Rusanov AL, Zgoda VG
Biomed Khim · 2023 Dec · PMID 38153053 · Publisher ↗
Plasma membrane proteins with extracellular-exposed domains are responsible for transduction of extracellular signals into intracellular responses, and their accessibility to therapeutic molecules makes them attractive t...
Plasma membrane proteins with extracellular-exposed domains are responsible for transduction of extracellular signals into intracellular responses, and their accessibility to therapeutic molecules makes them attractive targets for drug development. In this work, using omics technologies and immunochemical methods, we have studied changes in the content of markers of clusters of differentiation (CD markers) of neutrophils (CD33, CD97, CD54, CD38, CD18, CD11b, CD44, and CD71) at the level of transcripts and proteins in NB4, HL-60 and K562 cell lines, induced by the treatment with all-trans-retinoic acid (ATRA). Transcriptomic analysis revealed the induction of CD38, CD54, CD11b, and CD18 markers as early as 3 h after the addition of the inducer in the ATRA-responsive cell lines HL-60 and NB4. After 24 h, a line-specific expression pattern of CD markers could be observed in all cell lines. Studies of changes in the content of CD antigens by means of flow cytometry and targeted mass spectrometry (MS) gave similar results. The proteomic profile of the surface markers (CD38, CD54, CD11b, and CD18), characteristic of the NB4 and HL-60 lines, reflects different molecular pathways for the implementation of ATRA-induced differentiation of leukemic cells into mature neutrophils.
Secondary metabolites of plants and their possible role in the "age of superbugs".
Nesterovich VM, Belykh DA, Gorokhovets NV … +3 more , Kurbatov LK, Zamyatnin AA, Ikryannikova LN
Biomed Khim · 2023 Dec · PMID 38153052 · Publisher ↗
Bacterial infections are a serious cause of high morbidity and mortality worldwide. Over the past decades, the drug resistance of bacterial pathogens has been steadily increasing, while the rate of development of new eff...
Bacterial infections are a serious cause of high morbidity and mortality worldwide. Over the past decades, the drug resistance of bacterial pathogens has been steadily increasing, while the rate of development of new effective antibacterial drugs remains consistently low. The plant kingdom is sometimes called a bottomless well for the search for new antimicrobial therapies. This is due to the fact that plants are easily accessible and cheap to process, while extracts and components of plant origin often demonstrate a high level of biological activity with minor side effects. The variety of compounds obtained from plant raw materials can provide a wide choice of various chemical structures for interaction with various targets inside bacterial cells, while the rapid development of modern biotechnological tools opens the way to the targeted production of bioactive components with desired properties. The objective of this review is to answer the question, whether antimicrobials of plant origin have a chance to play the role of a panacea in the fight against infectious diseases in the "post-antibiotic era".
Problems and prospects for finding new pharmacological agents among adenosine receptor agonists, antagonists, or their allosteric modulators for the treatment of cardiovascular diseases.
Perfilova VN, Muzyko EA, Taran AS … +2 more , Shevchenko AA, Naumenko LV
Biomed Khim · 2023 Dec · PMID 38153051 · Publisher ↗
A1-adenosine receptors (A1AR) are widely distributed in the human body and mediate many different effects. They are abundantly present in the cardiovascular system, where they control angiogenesis, vascular tone, heart r...
A1-adenosine receptors (A1AR) are widely distributed in the human body and mediate many different effects. They are abundantly present in the cardiovascular system, where they control angiogenesis, vascular tone, heart rate, and conduction. This makes the cardiovascular system A1AR an attractive target for the treatment of cardiovascular diseases (CVD). The review summarizes the literature data on the structure and functioning of A1AR, and analyzes their involvement in the formation of myocardial hypertrophy, ischemia-reperfusion damage, various types of heart rhythm disorders, chronic heart failure, and arterial hypertension. Special attention is paid to the role of some allosteric regulators of A1AR as potential agents for the CVD treatment.
Redox regulation of the NLRP3-mediated inflammation and pyroptosis.
Rusetskaya NY, Loginova NY, Pokrovskaya EP … +2 more , Chesovskikh YS, Titova LE
Biomed Khim · 2023 Dec · PMID 38153050 · Publisher ↗
The review considers modern data on the mechanisms of activation and redox regulation of the NLRP3 inflammasome and gasdermins, as well as the role of selenium in these processes. Activation of the inflammasome and pyrop...
The review considers modern data on the mechanisms of activation and redox regulation of the NLRP3 inflammasome and gasdermins, as well as the role of selenium in these processes. Activation of the inflammasome and pyroptosis represent an evolutionarily conserved mechanism of the defense against pathogens, described for various types of cells and tissues (macrophages and monocytes, microglial cells and astrocytes, podocytes and parenchymal cells of the kidneys, periodontal tissues, osteoclasts and osteoblasts, as well as cells of the digestive and urogenital systems, etc.). Depending on the characteristics of redox regulation, the participants of NLRP3 inflammation and pyroptosis can be subdivided into 2 groups. Members of the first group block the mitochondrial electron transport chain, promote the formation of reactive oxygen species and the development of oxidative stress. This group includes granzymes, the mitochondrial antiviral signaling protein MAVS, and others. The second group includes thioredoxin interacting protein (TXNIP), erythroid-derived nuclear factor-2 (NRF2), Kelch-like ECH-associated protein 1 (Keap1), ninjurin (Ninj1), scramblase (TMEM16), inflammasome regulatory protein kinase NLRP3 (NEK7), caspase-1, gasdermins GSDM B, D and others. They have redox-sensitive domains and/or cysteine residues subjected to redox regulation, glutathionylation/deglutathionylation or other types of regulation. Suppression of oxidative stress and redox regulation of participants in NLRP3 inflammation and pyroptosis depends on the activity of the antioxidant enzymes glutathione peroxidase (GPX) and thioredoxin reductase (TRXR), containing a selenocysteine residue Sec in the active site. The expression of GPX and TRXR is regulated by NRF2 and depends on the concentration of selenium in the blood. Selenium deficiency causes ineffective translation of the Sec UGA codon, translation termination, and, consequently, synthesis of inactive selenoproteins, which can cause various types of programmed cell death: apoptosis of nerve cells and sperm, necroptosis of erythrocyte precursors, pyroptosis of infected myeloid cells, ferroptosis of T- and B-lymphocytes, kidney and pancreatic cells. In addition, suboptimal selenium concentrations in the blood (0.86 μM or 68 μg/l or less) have a significant impact on expression of more than two hundred and fifty genes as compared to the optimal selenium concentration (1.43 μM or 113 μg/l). Based on the above, we propose to consider blood selenium concentrations as an important parameter of redox homeostasis in the cell. Suboptimal blood selenium concentrations (or selenium deficiency states) should be used for assessment of the risk of developing inflammatory processes.
The prediction of main protease SARS-CoV-2 inhibition based on models of enzyme-inhibitor complexes.
Ivanova YO, Skvortsov VS
Biomed Khim · 2023 Nov · PMID 37937435 · Publisher ↗
A set of linear regression equations predicting the IC50 values for SARS-CoV-2 main protease inhibitors was analyzed. For 180 competitive inhibitors, we have simulated the molecular dynamics of enzyme-inhibitor complexes...
A set of linear regression equations predicting the IC50 values for SARS-CoV-2 main protease inhibitors was analyzed. For 180 competitive inhibitors, we have simulated the molecular dynamics of enzyme-inhibitor complexes with known structures or modeled using molecular docking. In the docking procedure, the selection of final poses was restricted by similarity to known structural analogs. The values of the energy contributions obtained by means of calculation of the free energy change of the enzyme-inhibitor complex performed by two variants of the MMPBSA (MMGBSA) method and a number of physicochemical characteristics of the inhibitors were used as independent variables. During the learning process, indicator variables were used for inhibitor subsets obtained from various literature sources to compensate the existing systematic deviations from the target value. A leave one out and leave 20% out cross validation procedures were used to evaluate the prediction quality. For the total logarithmic range width of 3.71, the mean error in predicting the lg(IC50) value was 0.45 log units. The stability of the prediction depending on the variability of the complex in molecular dynamics was investigated.
Contribution of the gasotransmitter nitric oxide to the structural and functional organization of erythrocytes under conditions of hypoxia/reoxygenation.
Akulich NV, Zinchuk VV
Biomed Khim · 2023 Nov · PMID 37937434 · Publisher ↗
Hypoxia is accompanied by changes in metabolism and cell functioning. Erythrocyte hemoglobin can be involved in adaptation to hypoxia by acting as an oxygen sensor, providing a link between oxygen content and blood circu...
Hypoxia is accompanied by changes in metabolism and cell functioning. Erythrocyte hemoglobin can be involved in adaptation to hypoxia by acting as an oxygen sensor, providing a link between oxygen content and blood circulation. The mechanisms providing this function have not been completely established. The purpose of this study was to evaluate the effect of the gasotransmitter nitric oxide on the structural and functional organization of erythrocytes under conditions of hypoxia/reoxygenation. NO participated in adaptive reactions under hypoxia/reoxygenation conditions by changing hemoglobin conformation, followed by changes in hemoprotein spectral characteristics and hemoglobin affinity to oxygen together with increasing anisocytosis, volume and cell surface. The increase in intracellular NO concentrations under hypoxic conditions was provided by extracellular fluid nitrites. Molsidomine (a NO donor) induced a higher NO increase without involvement of the nitrite reductase mechanism, it caused an increase in the average erythrocyte volume, anisocytosis, and an increase in the cell surface.
Serum miR-181a and miR-25 in patients with malignant and benign breast diseases.
Perepechaeva ML, Studenikina AA, Grishanova AY … +4 more , Glushkov AN, Polenok EG, Bajramov PV, Autenshlyus AI
Biomed Khim · 2023 Nov · PMID 37937433 · Publisher ↗
Breast tumor diseases include a wide range of pathologies that require different approaches to their treatment. MicroRNA (miR) levels, reflecting regulation of the gene expression involved in tumorigenesis, can be diagno...
Breast tumor diseases include a wide range of pathologies that require different approaches to their treatment. MicroRNA (miR) levels, reflecting regulation of the gene expression involved in tumorigenesis, can be diagnostic and prognostic markers of breast diseases. The levels of circulating miR-181a and miR-25 were measured in patients with benign breast diseases (BBD), patients with invasive carcinoma of a nonspecific type (ICNT) and also in conditionally healthy women. Expression of both miRs was higher in patients of both groups as compared to controls; at the same time, the content of serum miR-181a and miR-25 was higher in BBD patients than in ICNT patients. The detected changes may be of interest in the context of precancerous changes in BBD. It seems possible to use them in the future as markers of the pathological process as a part of a large diagnostic panel.
Interleukin-1β and TNF-α are elevated in the amygdala of adult rats prenatally exposed to ethanol.
Kokhan VS, Anokhin PK, Proskuryakova TV … +3 more , Shokhonova VA, Ageldinov RA, Shamakina IY
Biomed Khim · 2023 Nov · PMID 37937432 · Publisher ↗
Affective disorders, including anxiety and depression, developed in adult offspring of the mothers who consumed alcohol during pregnancy could be associated with an imbalance in neuroimmune factors in the amygdala (corpu...
Affective disorders, including anxiety and depression, developed in adult offspring of the mothers who consumed alcohol during pregnancy could be associated with an imbalance in neuroimmune factors in the amygdala (corpus amygdaloideum) resulted in impaired emotional stimulus processing. The aim of this study was to compare the content of cytokines TNF-α, IL-1α, IL-1β, IL-10, and IL-17 in the amygdala of adult female rats exposed to alcohol in utero and control rats. Cytokine levels were evaluated using a multiplex immunoassay system; mRNA expression was investigated using a real-time reverse transcription-polymerase chain reaction (RT-qPCR) assay. Prenatal alcohol exposure led to the increase in the content of TNF-α and IL-1β without significant changes in the mRNA expression level. Our data suggest that ethanol exposure to the fetus during pregnancy can result in long-term alterations in the content of the key neuroinflammatory factors in the amygdala, which in turn can be a risk factor for affective disorders in the adulthood.
Neuroprotective effects of isatin and afobazole in rats with rotenone-induced Parkinsonism are accompanied by increased brain levels of Triton X-100 soluble alpha-synuclein.
Buneeva OA, Kapitsa IG, Zgoda VG … +1 more , Medvedev AE
Biomed Khim · 2023 Nov · PMID 37937431 · Publisher ↗
Effects of the endogenous neuroprotector isatin and the pharmacological drug afobazole (exhibiting neuroprotective properties) on behavioral reactions and quantitative changes in the brain proteomic profile have been inv...
Effects of the endogenous neuroprotector isatin and the pharmacological drug afobazole (exhibiting neuroprotective properties) on behavioral reactions and quantitative changes in the brain proteomic profile have been investigated in rats with experimental rotenone Parkinsonism. A single dose of isatin (100 mg/kg subcutaneously on the last day of a 7-day course of rotenone administration) improved the motor activity of rats with rotenone-induced Parkinsonism in the open field test (horizontal movements) and the rotating rod test. Afobazole (10 mg/kg intraperitoneally, daily during the 7-day course of rotenone administration) reduced the manifestations of rigidity and postural instability. Proteomic analysis, performed using brain samples obtained the day after the last administration of rotenone and neuroprotectors, revealed similar quantitative changes in the brain of rats with rotenone Parkinsonism. An increase in the relative content of 65 proteins and a decrease in the relative content of 21 proteins were detected. The most pronounced changes - an almost ninety-fold increase in the alpha-synuclein content - were found in the brains of rats treated with isatin. In animals of the experimental groups treated with "Rotenone + Isatin", as well as "Rotenone + Afobazole", the increase in the relative content of this protein in the brain was almost 60 and 50 times higher than the control values. Taking into consideration the known data on the physiological role of alpha-synuclein, an increase in the content of this protein in the brain upon administration of neuroprotectors to animals with rotenone Parkinsonism may represent a compensatory reaction, at least in the early stages of this disease and the beginning of its treatment.
The flavonoids fisetin, apigenin, kaempferol, naringenin, naringin regulate respiratory activity and membrane potential of rat liver mitochondria and inhibit oxidative processes in erythrocytes.
Savko AI, Ilyich TV, Veiko AG … +3 more , Kovalenia TA, Lapshina EA, Zavodnik IB
Biomed Khim · 2023 Nov · PMID 37937430 · Publisher ↗
Flavonoids, secondary plant metabolites, represent the most abundant heterogeneous group of phytochemicals. The aim of this study to compare antioxidant activity and regulatory properties of several representatives of di...
Flavonoids, secondary plant metabolites, represent the most abundant heterogeneous group of phytochemicals. The aim of this study to compare antioxidant activity and regulatory properties of several representatives of different classes of flavonoids, fisetin, apigenin, kaempferol, naringenin, naringin, using liver mitochondria and erythrocytes as research objects. In the concentration range of 2.5-25 μM fisetin, apigenin, kaempferol, naringenin, and naringin dose-dependently prevented oxidative damage of erythrocytes induced by 700 μM tert-butyl hydroperoxide: accumulation of lipid peroxidation (LPO) products and oxidation of glutathione GSH. The IC50 values corresponding to the flavonoid concentration inhibiting the LPO process in erythrocyte membranes by 50%, were 3.9±0.8 μM in the case of fisetin, 6.5±1.6 μM in the case of kaempferol, 8.1±2.1 μM in the case of apigenin, 37.8±4.4 μM in the case of naringenin, and 64.7±8.6 μM in the case of naringin. The antioxidant effect of flavonoids was significantly higher in the membrane structures compared to the cytoplasm of cells. All flavonoids studied (10-50 μM) effectively inhibited the respiratory activity of isolated rat liver mitochondria and, with the exception of kaempferol, stimulated Ca²⁺-induced dissipation of the mitochondrial membrane potential. Cyclosporine A and ruthenium red inhibited flavonoid-stimulated Ca²⁺-dependent membrane depolarization, thus indicating that the mitochondrial calcium uniporter and the mitochondrial permeability transition pore opening were involved in the flavonoid effects. Flavonoids, as the redox-active compounds with antioxidant properties, are able to regulate mitochondrial potential and respiratory activity, and prevent mitochondrial oxidative stress. They can be considered as effective pharmacological agents or nutraceuticals.
Perspectives for the creation of a new type of vaccine preparations based on pseudovirus particles using polio vaccine as an example.
Zhdanov DD, Ivin YY, Shishparenok AN … +9 more , Kraevskiy SV, Kanashenko SL, Agafonova LE, Shumyantseva VV, Gnedenko OV, Pinyaeva AN, Kovpak AA, Ishmukhametov AA, Archakov AI
Biomed Khim · 2023 Nov · PMID 37937429 · Publisher ↗
Traditional antiviral vaccines are currently created by inactivating the virus chemically, most often using formaldehyde or β-propiolactone. These approaches are not optimal since they negatively affect the safety of the...
Traditional antiviral vaccines are currently created by inactivating the virus chemically, most often using formaldehyde or β-propiolactone. These approaches are not optimal since they negatively affect the safety of the antigenic determinants of the inactivated particles and require additional purification stages. The most promising platforms for creating vaccines are based on pseudoviruses, i.e., viruses that have completely preserved the outer shell (capsid), while losing the ability to reproduce owing to the destruction of the genome. The irradiation of viruses with electron beam is the optimal way to create pseudoviral particles. In this review, with the example of the poliovirus, the main algorithms that can be applied to characterize pseudoviral particles functionally and structurally in the process of creating a vaccine preparation are presented. These algorithms are, namely, the analysis of the degree of genome destruction and coimmunogenicity. The structure of the poliovirus and methods of its inactivation are considered. Methods for assessing residual infectivity and immunogenicity are proposed for the functional characterization of pseudoviruses. Genome integrity analysis approaches, atomic force and electron microscopy, surface plasmon resonance, and bioelectrochemical methods are crucial to structural characterization of the pseudovirus particles.
Alpha-2 macroglobulin activity in SARS-CoV-2 induced infection and in the post-COVID-19 period.
Akbasheva OE, Mitrofanova DK, Spirina LV … +4 more , Samoilova YG, Matveeva MV, Podchinenova DV, Oleynik OA
Biomed Khim · 2023 Sep · PMID 37705485 · Publisher ↗
The universal proteinase inhibitor α2-macroglobulin (α₂-MG) exhibiting antiviral and immunomodulatory activities, is considered as an important participant in the infectious process. The activity of α₂-MG in the new coro...
The universal proteinase inhibitor α2-macroglobulin (α₂-MG) exhibiting antiviral and immunomodulatory activities, is considered as an important participant in the infectious process. The activity of α₂-MG in the new coronavirus infection and post-covid syndrome (long COVID) has not been studied yet. We examined 85 patients diagnosed with community-acquired bilateral polysegmental pneumonia developed under conditions of a new coronavirus infection SARS-CoV-2. For assessment of the post-COVID period, 60 patients were examined 5.0±3.6 months after the coronavirus infection. Among these patients, 40 people had complications, manifested in the form of neurological, cardiological, gastroenterological, dermatological, bronchopulmonary symptoms. The control group included 30 conditionally healthy individuals with a negative PCR result for SARS-CoV-2 RNA and lack of antibodies to the SARS-CoV-2 virus. The α₂-MG activity in serum samples of patients with coronavirus infection dramatically decreased, up to 2.5% of the physiological level. This was accompanied by an increase in the activity of the α₁-proteinase inhibitor, elastase- and trypsin-like proteinases by 2.0-, 4.4- and 2.6-fold respectively as compared with these parameters in conditionally healthy individuals of the control. In the post-COVID period, despite the trend towards normalization of the activity of inhibitors, the activity of elastase-like and especially trypsin-like proteinases in serum remained elevated. In overweight individuals, the increase in the activity of trypsin-like proteinases was most pronounced and correlated with an increase in the antibody titer to the SARS-CoV-2 virus. In the post-COVID period, the α₂-MG activity not only normalized, but also exceeded the control level, especially in patients with dermatological and neurological symptoms. In patients with neurological symptoms or with dermatological symptoms, the α₂-MG activity was 1.3 times and 2.1 times higher than in asymptomatic persons. Low α₂-MG activity in the post-COVID period persisted in overweight individuals. The results obtained can be used to monitor the course of the post-COVID period and identify risk groups for complications.
Prolonged alcohol consumption influences microRNA expression in the nucleus accumbens of the rat brain.
Airapetov MI, Eresko SO, Shamaeva SA … +4 more , Matveev NM, Bychkov ER, Lebedev AA, Shabanov PD
Biomed Khim · 2023 Sep · PMID 37705484 · Publisher ↗
The microRNA (miR) species analyzed in this study are involved in molecular mechanisms of TLR4 and TLR7 signaling, mediating the development of neuroinflammation and neurodegeneration. We have investigated the expression...
The microRNA (miR) species analyzed in this study are involved in molecular mechanisms of TLR4 and TLR7 signaling, mediating the development of neuroinflammation and neurodegeneration. We have investigated the expression levels of miR-let7b, miR-96, miR-182, miR-155, and the mRNA content of HMGB1, TLR3, TLR4 in the nucleus accumbens (NAc) of the brain of rats exposed to long-term alcoholization. The long-term alcoholization caused a decrease in miR-let7b, miR-96, miR-182, and TLR7 mRNA levels; this was accompanied by an increase in miR-155, TLR4, and Hmgb1 mRNA levels in the NAc of rat brain. TLR7 is functionally linked to miR-let7b. The data of a simultaneous decrease in miR-let7b and TLR7 mRNA are of interest for further studies; they may indicate on the lack of functionally significant links between Hmgb1 and the miR-let7b-TLR7 system in NAc. The existing evidence of a functional relationship between TLR4 with miR-155 and miR-182 and our observations on their expression changes during chronic alcoholization are very interesting and require further investigation. The suggestion about the development of neuroinflammatory process in NAc under prolonged alcohol exposure are relevant for studying the level of TLR gene expression in NAc, as well as the expression of miR species, which may have a functional relationship with the TLR system.
The effect of rifampicin on expression of the toll-like receptor system genes in the forebrain cortex of rats prenatally exposed to alcohol.
Airapetov MI, Eresko SO, Ignatova PD … +6 more , Skabelkin DA, Mikhailova AA, Ganshina DA, Lebedev AA, Bychkov ER, Shabanov PD
Biomed Khim · 2023 Sep · PMID 37705483 · Publisher ↗
Ethanol causes long-term changes in the toll-like receptor (TLR) system, promoting activation of neuroinflammation pathways. Alcohol use during pregnancy causes neuroinflammatory processes in the fetus; this can lead to...
Ethanol causes long-term changes in the toll-like receptor (TLR) system, promoting activation of neuroinflammation pathways. Alcohol use during pregnancy causes neuroinflammatory processes in the fetus; this can lead to the development of symptoms of fetal alcohol spectrum disorder (FASD). Our study has shown that prenatal alcohol exposure (PAE) induced long-term changes in the TLR system genes (Tlr3, Tlr4, Ticam, Hmgb1, cytokine genes) in the forebrain cortex of rat pups. Administration of rifampicin (Rif), which can reduce the level of pro-inflammatory mediators in various pathological conditions of the nervous system, normalized the altered expression level of the studied TLR system genes. This suggests that Rif can prevent the development of persistent neuroinflammatory events in the forebrain cortex of rat pups caused by dysregulation in the TLR system.
The immunomodulatory activity of the betulonic acid based compound.
Mosalev KI, Ivanov ID, Miroshnichenko SM … +4 more , Tenditnik MV, Bgatova NP, Shults EE, Vavilin VA
Biomed Khim · 2023 Sep · PMID 37705482 · Publisher ↗
The immunomodulatory activity of a betulonic acid-based compound with furocoumarin (BABCF; 2-azido, 9-N-methylpiperazinomethyl oreozelone) has been investigated. Male C57BL/6 mice (aged 3 months) treated with the cytosta...
The immunomodulatory activity of a betulonic acid-based compound with furocoumarin (BABCF; 2-azido, 9-N-methylpiperazinomethyl oreozelone) has been investigated. Male C57BL/6 mice (aged 3 months) treated with the cytostatic agent cyclophosphamide (CP) and intact individuals served as experimental models. The expression of genes was studied in bone marrow (IL-12, IL-10, IL-1β, TNF-α, TGF-β, M-CSF, GM-CSF) or in the suspension of peritoneal cells (IL-12, IL-10; as the injection site). The surface markers of T-lymphocytes (CD3, CD4, and CD8) in fractions of venous blood mononuclear cells (MNCs) were determined by means of flow cytometry using antibodies. Histological and morphometric studies were performed to assess the impact of CP and BABCF on the thymus. BABCF caused a pronounced (about 3-fold) increase in relative expression of the GM-KSF gene. BABCF caused a local increase in the expression of IL-12 in the peritoneal cavity cells and restored the relative content of T-lymphocytes in the blood of CP-treated mice treated affecting mainly CD3⁺CD4⁺ lymphocytes. This substance reduced the tissue density of the thymic cortex and thymic medulla in CP-treated mice. Thus, results of this study suggest that BABCF exhibits a stimulating effect on the cellular link of immunity and promotes maintenance of the number of T-lymphocytes in the blood due to their migration from the central organs of the immune system.
Iron metabolism in the cell as a target in the development of potential antimicrobial and antiviral agents.
Blagodarov SV, Zheltukhina GA, Nebolsin VE
Biomed Khim · 2023 Sep · PMID 37705481 · Publisher ↗
The search and creation of innovative antimicrobial drugs, acting against resistant and multiresistant strains of bacteria and fungi, are one of the most important tasks of modern bioorganic chemistry and pharmaceuticals...
The search and creation of innovative antimicrobial drugs, acting against resistant and multiresistant strains of bacteria and fungi, are one of the most important tasks of modern bioorganic chemistry and pharmaceuticals. Since iron is essential for the vital activity of almost all organisms, including mammals and bacteria, the proteins involved in its metabolism can serve as potential targets in the development of new promising antimicrobial agents. Such targets include endogenous mammalian biomolecules, heme oxygenases, siderophores, protein 24p3, as well as bacterial heme oxygenases and siderophores. Other proteins that are responsible for the delivery of iron to cells and its balance between bacteria and the host organism also attract certain particular interest. The review summarizes data on the development of inhibitors and inducers (activators) of heme oxygenases, selective for mammals and bacteria, and considers the characteristic features of their mechanisms of action and structure. Based on the reviewed literature data, it was concluded that the use of hemin, the most powerful hemooxygenase inducer, and its derivatives as potential antimicrobial and antiviral agents, in particular against COVID-19 and other dangerous infections, would be a promising approach. In this case, an important role is attributed to the products of hemin degradation formed by heme oxygenases in vitro and in vivo. Certain attention has been paid to the data on the antimicrobial action of iron-free protoporphyrinates, namely complexes with Co, Ga, Zn, Mn, their advantages and disadvantages compared to hemin. Modification of the well-known antibiotic ceftazidime with a siderophore molecule increased its effectiveness against resistant bacteria.
Quantitative changes of brain isatin-binding proteins of rats with the rotenone-induced experimental parkinsonism.
Buneeva OA, Kapitsa IG, Kazieva LS … +2 more , Vavilov NE, Zgoda VG
Biomed Khim · 2023 Jun · PMID 37384911 · Publisher ↗
Isatin (indoldione-2,3) is an endogenous regulator found in humans and animals. It exhibits a broad range of biological activity mediated by numerous isatin-binding proteins. Isatin produces neuroprotective effects in se...
Isatin (indoldione-2,3) is an endogenous regulator found in humans and animals. It exhibits a broad range of biological activity mediated by numerous isatin-binding proteins. Isatin produces neuroprotective effects in several experimental models of diseases, including Parkinsonism induced by the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine).Rotenone (a neurotoxin used to modeling Parkinson's disease in rodents) causes significant changes in the profile of isatin-binding proteins of rat brain. Comparative proteomic identification of brain proteins of control rats and the rats with the rotenone-induced Parkinsonian syndrome (PS) revealed significant quantitative changes of 86 proteins under the influence of rotenone. This neurotoxin mainly caused the increase of the quantity of proteins involved in signal transduction and regulation of enzyme activity (24), proteins involved in cytoskeleton formation and exocytosis (23), and enzymes involved in energy generation and carbohydrate metabolism (19). However, only 11 of these proteins referred to isatin-binding proteins; the content of eight of them increased while the content of three proteins decreased. This suggests that the dramatic change of the profile of isatin-binding proteins, found in the development of the rotenone-induced PS, comes from changes in the state of the pre-existing molecules of proteins, rather than altered expression of corresponding genes.
The effect of renalase-derived peptides on viability of HepG₂ and PC3 cells.
Fedchenko VI, Morozevich GE, Medvedev AE
Biomed Khim · 2023 Jun · PMID 37384910 · Publisher ↗
Renalase (RNLS) is a recently discovered protein, which plays different roles inside and outside cells. Intracellular RNLS is a FAD-dependent oxidoreductase (EC 1.6.3.5), while extracellular RNLS lacks its N-terminal pep...
Renalase (RNLS) is a recently discovered protein, which plays different roles inside and outside cells. Intracellular RNLS is a FAD-dependent oxidoreductase (EC 1.6.3.5), while extracellular RNLS lacks its N-terminal peptide, FAD cofactor, and exhibits various protective effects in a non-catalytic manner. Certain evidence exists, that plasma/serum RNLS is not an intact protein secreted into the extracellular space, and exogenous recombinant RNLS is effectively degraded during short-term incubation with human plasma samples. Some synthetic analogues of the RNLS sequence (e.g. the Desir's peptide RP-220, a 20-mer peptide corresponding to the RNLS sequence 220-239) have effects on cell survival. This suggests that RNLS-derived peptides, formed during proteolytic processing, may have own biological activity. Based on results of a recent bioinformatics analysis of potential cleavage sites of RNLS (Fedchenko et al., Medical Hypotheses, 2022) we have investigated the effect of four RNLS-derived peptides as well as RP-220 and its fragment (RP-224) on the viability of two cancer cell lines: HepG₂ (human hepatoma) and PC3 (prostate cancer). Two RNLS-derived peptides (RP-207 and RP-220) decreased the viability of HepG₂ cells in a concentration dependent manner. The most pronounced and statistically significant effect (30-40% inhibition of cell growth) was observed at 50 μM concentration of each peptide. In the experiments with PC3 cells five of six RNLS-derived peptides had a significant impact on the cell viability. RP-220 and RP-224 decreased cell viability; however, no concentration dependence of this effect was observed in the range of concentrations studied (1-50 μM). Three other RNLS-derived peptides (RP-207, RP-233, and RP-265) increased viability of PC3 cells by 20-30%, but no concentration-dependence of this effect was found. Data obtained suggest that some RNLS-derived peptides may influence the viability of various cells and manifestation and direction of the effect (increase of decrease of the cell viability) is cell-type-specific.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe