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Role of Caspases in the Cytotoxicity of NK-92 Cells in Various Models of Coculturing with Trophoblasts
In this study, we examined changes in the content of caspases and studied activation of these enzymes in Jeg-3 trophoblasts in various models of their coculturing with NK-92 cells and demonstrated the necessity of direct contact between these cell populations for the activation of caspase-8 and caspase-3 in the trophoblasts. Contact coculturing of the two cell lines resulted in the appearance of the cytotoxic protein granzyme B in Jeg-3 cells that was accompanied by a decrease in the content of this enzyme in NK-92 cells. Distant coculturing of NK-92 and Jeg-3 cells did not trigger initiator and effector caspases character...
Source: Biochemistry (Moscow) - October 1, 2019 Category: Biochemistry Source Type: research

Enhanced Platelet Sensitivity to IGF-1 in Patients with Type 2 Diabetes Mellitus
AbstractDiabetes mellitus is characterized by increased platelet activation which is determined by many factors including changes in the expression of membrane proteins. The aim of this study was to investigate the sensitivity of human platelets to the insulin-like growth factor (IGF) system in patients with poorly controlled type 2 diabetes mellitus (DM2). Ligand binding was analyzed using125I-labelled IGF-1 and insulin, and relative expression of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) was evaluated by Western blotting. Platelet aggregation in the presence of IGF-1 was studied by the plat...
Source: Biochemistry (Moscow) - October 1, 2019 Category: Biochemistry Source Type: research

Changes in the Receptor-Binding Properties of H3N2 Viruses during Long-Term Circulation in Humans
In this study, we demonstrated that the ability to bind the Neu5Gc-terminated receptor is related to the amino acid 145: viruses of years 1972 –1999 with Lysl45bindto the receptor, whereas viruses with Asnl 45 do not. Sporadic appearance and disappearance of the ability to bind Neu5Gc oligosaccharides and the absence of Neu5Gc in the composition of human glycoconjugates indicate the non-adaptive nature of this ability. It was previously shown that unlike H1N1 viruses, H3N2 viruses of years 1968–1989 did not distinguish between Neu5Acα2-6Galβ1-4Glc (6′SL) and Neu5Acα2-6Galβ1-4GlcNAc (...
Source: Biochemistry (Moscow) - October 1, 2019 Category: Biochemistry Source Type: research

The Mechanisms of Regulation of Aerobic Glycolysis (Warburg Effect) by Oncoproteins in Carcinogenesis
AbstractAccording to modern concepts, tumor formation is associated with impairments in the structure of protooncogenes and/or deactivation of suppressor genes, regardless of the nature of carcinogenic factor. As a consequence, unregulated onco-proteins activate extracellular proteases, resulting in the destruction of the extracellular matrix, which facilitates cell invasion, deterioration of the cell-cell contacts, and metastasis. Tumor development requires activation of certain transcription factors; however, many oncoproteins are not transcription factors. It can be assumed that these oncoproteins are not the ultimate e...
Source: Biochemistry (Moscow) - October 1, 2019 Category: Biochemistry Source Type: research

Changes in the Metabolism of Sphingoid Bases in the Brain and Spinal Cord of Transgenic FUS(1-359) Mice, a Model of Amyotrophic Lateral Sclerosis
AbstractThe aim of this study was to evaluate changes in the content of sphingoid bases - sphingosine (SPH), sphinga-nine, and sphingosine-1-phosphate (SPH-1-P) - and in expression of genes encoding enzymes involved in their metabolism in the brain structures (hippocampus, cortex, and cerebellum) and spinal cord of transgenic FUS(1-359) mice. FUS(1-359) mice are characterized by motor impairments and can be used as a model of amyotrophic lateral sclerosis (ALS). Lipids from the mouse brain structures and spinal cord after 2, 3, and 4 months of disease development were analyzed by chro-matography/mass spectrometry, while ch...
Source: Biochemistry (Moscow) - October 1, 2019 Category: Biochemistry Source Type: research

Prolactin Signaling Pathways Determining Its Direct Effects on Kidneys in the Cholestasis of Pregnancy Model
AbstractCholestasis of pregnancy is a pathology associated with disruptions in the bile flow and dysregulation of salt and water homeostasis. Prolactin is one of the most important regulators of salt and water balance. Changes in the expression of long and short isoforms of the prolactin receptor (PrlR) and mediators of prolactin signaling were studied by immunoblotting and RT-qPCR in the rat kidney cortex and outer medulla in the model of cholestasis of pregnancy. Both PrlR isoforms were shown to participate in the effects of prolactin in cholestasis of pregnancy. Direct impact of prolactin on the kidney has been demonstr...
Source: Biochemistry (Moscow) - October 1, 2019 Category: Biochemistry Source Type: research

Modern Perspective on Metabolic Reprogramming in Malignant Neoplasms
AbstractMetabolic reprogramming is one of the central features of transformed cells. Elucidation of interactions between oncogenic signaling and cell metabolic processes has become the basis for extensive studies of metabolism reprogramming in tumor tissue. The review summarizes the key results of studies on the catabolic and anabolic rearrangements in tumor cells with special emphasis on carbohydrate, lipid, amino acid, and acetate metabolism determining the cancer phenotype of cells. (Source: Biochemistry (Moscow))
Source: Biochemistry (Moscow) - October 1, 2019 Category: Biochemistry Source Type: research

Protonophoric and Photodynamic Effects of Fluorescein Decyl(triphenyl)phosphonium Ester on the Electrical Activity of Pond Snail Neurons
AbstractUncouplers of oxidative phosphorylation in mitochondria, which have been essential in elucidating the basic principles of cell bioenergetics, have recently attracted a considerable interest as compounds with therapeutic, e.g., neuro-protective, properties. Here, we report the effect of mitofluorescein (mitoFluo), a new protonophoric uncoupler representing a conjugate of fluorescein with decyl(triphenyl)phosphonium, on the electrical activity of neurons fromLymnaea stagnalis. Incubation with mitoFluo in the dark led to a decrease in the absolute value of the resting membrane potential of the neurons and alterations ...
Source: Biochemistry (Moscow) - October 1, 2019 Category: Biochemistry Source Type: research

Effect of Benzo(a)pyrene on the Expression of miR-483-3p in Hepatocyte Primary Culture and Rat Liver
AbstractHere, we suggested that the epigenetic mechanism of benzo(a)pyrene (BP) action might be based on the aryl hydrocarbon receptor (AhR)-mediated transcription of the target genes, including miRNAs, that have the dioxin response element (DRE) in their promoters. The effect of BP on the expression of the oncogenic miR-483-3p, its host geneIGF2, and target geneIGF1 in primary hepatocytes and in the liver of Wistar female rats was investigated. The activation of AhR was confirmed using selective AhR inhibitor CH-223191 and by evaluating expression of the targetCYP1A1 gene. The lack of coordination between the expression o...
Source: Biochemistry (Moscow) - October 1, 2019 Category: Biochemistry Source Type: research

Mitochondrial Translation Initiation Factor 3: Structure, Functions, Interactions, and Implication in Human Health and Disease
AbstractMitochondria are essential organelles of eukaryotic cell that provide its respiratory function by means of the electron transfer chain. Expression of mitochondrial genes is organized in a bacterial-like manner; however multiple evolutionary differences are observed between the two systems, including translation initiation machinery. This review is dedicated to the mitochondrial translation initiation factor 3 (IF3mt), which plays a key role in the protein synthesis in mitochondria. Involvement of IF3mt in human health and disease is discussed. (Source: Biochemistry (Moscow))
Source: Biochemistry (Moscow) - October 1, 2019 Category: Biochemistry Source Type: research

Comparative Whole-Transcriptome Profiling of Liver Tissue from Wistar Rats Fed with Diets Containing Different Amounts of Fat, Fructose, and Cholesterol
AbstractDifferential expression of 30,003 genes was studied in the liver of female Wistar rats fed with isocaloric diets with the excess of fat, fructose, or cholesterol, or their combinations for 62 days using the method of whole-transcriptome pro-filing on a microchip. Relative mRNA expression levels of theAsah2,Crot,Crtc2,Fmo3,GSTA2,LOC1009122026,LOC102551184,NpY,NqO1,Prom1,Retsat,RGD1305464,Tmem104, andWhsc1 genes were also determined by RT-qPCR. All the tested diets affected differently the key metabolic pathways (KEGGs). Significant changes in the expression of steroid metabolism gene were observed in the liver of an...
Source: Biochemistry (Moscow) - September 1, 2019 Category: Biochemistry Source Type: research

Receptor Functions of Semaphorin 4D
AbstractSemaphorin 4D (Sema4D) is a multifunctional protein widely expressed in an organism that plays an important role in the control of many physiological and pathological processes, including immunoregulation, neurogenesis, angiogenesis, and tumor progression. It was first described almost 30 years ago and has been actively studied since then. However, with rare exceptions, all studies of the Sema4D activity proceed from the assumption that semaphorin is a ligand that acts through specific receptors (CD72 and plexins) and that the main targets of Sema4D in different tissues are cells that carry these receptors on the m...
Source: Biochemistry (Moscow) - September 1, 2019 Category: Biochemistry Source Type: research

Electron Transfer on the Donor Side of Manganese-Depleted Photosystem 2
AbstractAfter removal of manganese ions responsible for light-driven water oxidation, redox-active tyrosine YZ (tyrosine 161 of the D1 subunit) still remains the dominant electron donor to the photooxidized chlorophyll P680 ($${\rm{P}}_{680}^+$$) in the reaction center of photosystem 2 (PS2). Here, we investigated$${\rm{P}}_{680}^+$$ reduction by YZ under single-turnover flashes in Mn-depleted PS2 core complexes in the presence of weak acids and NH4Cl. Analysis of changes in the light-induced absorption at 830 nm (reflecting P680 redox transitions) at pH 6.0 showed that$${\rm{P}}_{680}^+$$ reduction is well approximated by...
Source: Biochemistry (Moscow) - September 1, 2019 Category: Biochemistry Source Type: research

Spectral and Photochemical Properties of Rhodobacter sphaeroides R-26 Reaction Center Films in Vacuum
AbstractUsing absorption spectroscopy in the visible/near-IR and mid-IR regions, spectral and photochemical properties of isolated reaction centers (RCs) fromRhodobacter sphaeroides R-26 were studied in dried films on the inorganic support surface (quartz or CaF2 plates) under vacuum dehydration conditions (10−2 or 7 ·10−5 mm Hg). Three detergents,N,N-dimethyldodecylamineN-oxide (LDAO), Triton X-100 (TX100), andn-dodecyl- β-D-maltoside (DM), were tested for their ability to stabilize the RC–detergent complexes in the vacuum-dried state. It was shown that in the presence of LDAO, RC complexes u...
Source: Biochemistry (Moscow) - September 1, 2019 Category: Biochemistry Source Type: research

Low Ouabain Doses and AMP-Activated Protein Kinase as Factors Supporting Electrogenesis in Skeletal Muscle
AbstractMany motor disorders are associated with depolarization of the membrane of skeletal muscle fibers due to the impaired functioning of Na,K-ATPase. Here, we studied the role of ouabain (specific Na,K-ATPase ligand) and AMP-activated protein kinase (key regulator of muscle metabolism) in the maintenance of muscle electrogenesis; the levels of these endogenous factors are directly related to the motor activity. After 4-day intraperitoneal administration of ouabain (1 μg/kg daily), a hyperpolarization of sarcolemma was registered in isolated rat diaphragm muscles due to an increase in the electrogenic activity of Na,...
Source: Biochemistry (Moscow) - September 1, 2019 Category: Biochemistry Source Type: research

Post-translational Modifications of Nucleotide Excision Repair Proteins and Their Role in the DNA Repair
AbstractNucleotide excision repair (NER) is one of the major DNA repair pathways aimed at maintaining genome stability. Correction of DNA damage by the NER system is a multistage process that proceeds with the formation of multiple DNA-protein and protein-protein intermediate complexes and requires precise coordination and regulation. NER proteins undergo post-translational modifications, such as ubiquitination, sumoylation, phosphorylation, acetylation, and poly(ADP-ribosyl)ation. These modifications affect the interaction of NER factors with DNA and other proteins and thus regulate either their recruitment into the compl...
Source: Biochemistry (Moscow) - September 1, 2019 Category: Biochemistry Source Type: research

Jasmonic Acid Induces Endoplasmic Reticulum Stress with Different Outcome in Cultured Normal and Tumor Epidermal Cells
AbstractPlant hormones produce cytotoxic effect on human cells and can trigger the processes unrelated to cell death, e.g., biosynthetic system stress. The goal of this study was to investigate activation of the endoplasmic reticulum (ER) stress by jasmonic acid (JA) and to distinguish between the responses of cultured immortalized non-tumorigenic HaCaT cells and epidermoid carcinoma A431 cells to this plant hormone. JA was used in the concentration of 2 mM, as it suppressed cell proliferation in both cell lines. We analyzed expression of genes associated with the activation of ER stress (GRP78,ATF4,CHOP), the structure of...
Source: Biochemistry (Moscow) - September 1, 2019 Category: Biochemistry Source Type: research

Methods for Correction of the Single-Nucleotide Substitution c.840C & gt;T in Exon 7 of the SMN2 Gene
The objective of this study was to create and test gene-editing systems for correction of the single-nucleotide substitution c.840C>T in exon 7 of theSMN2 gene in fibroblasts, induced pluripotent stem cells, and motor neuron progenitors derived from a SMA patient. For this purpose, we used plasmid vectors expressing CRISPR/Cas9 and CRISPR/Cpf1, plasmid donor, and 90-nt single-stranded oligonucleotide templates that were delivered to the target cells by electroporation. Although sgRNA_T2 and sgRNA_T3 guiding RNAs were more efficient than sgRNA_T1 in fibroblasts (p
Source: Biochemistry (Moscow) - September 1, 2019 Category: Biochemistry Source Type: research

Mechanisms of Antiphospholipid Syndrome Induction: Role of NKT Cells
AbstractThe review discusses the mechanisms of participation of natural killer T cells (NKT cells) in the induction of antiphospholipid antibodies (APA) that play a major pathogenetic role in the formation of antiphospholipid syndrome (APS), summarizes the data on APS pathogenesis, and presents modern concepts on the antibody formation involving follicular helper type II NK cells. (Source: Biochemistry (Moscow))
Source: Biochemistry (Moscow) - September 1, 2019 Category: Biochemistry Source Type: research

Polymorphism of the IL-1 β, TNF, IL-1RA and IL-4 Cytokine Genes Significantly Increases the Risk of Preterm Birth
The objective of our study was to find the association between polymorphic markers in the cytokine IL- β, TNF-α, IL-1Ra, and IL-4 genes and development of preterm labor. The prospective study was conducted in 108 pregnant women with the risk of preterm birth. The main group consisted of 66 women whose pregnancy ended with preterm delivery despite the ongoing therapy. The comparison group included 4 2 women with the full-term delivery. The dominant T allele of the cytokine IL-1β gene polymorphism rs1143634 (3953C→T) was 7.6 times more common in women with preterm delivery vs. the comparison group (36.4 ...
Source: Biochemistry (Moscow) - September 1, 2019 Category: Biochemistry Source Type: research

The Role of Plasminogen Activator System in the Pathogenesis of Epilepsy
AbstractNeurodegenerative disorders and ischemic conditions leading to the development of Alzheimer ’s and Parkinson’s diseases, vascular dementia, etc. have attracted attention of many researchers studying the mechanisms of abnormalities in the central nervous system (CNS). The genetic predisposition for these diseases has been reported in the studies of the last few decades. Current achievem ents in biochemistry and molecular biology have revealed the relationships between risk factors contributing to the development of these pathologies and target proteins controlled by the genome. It has been demonstrated t...
Source: Biochemistry (Moscow) - September 1, 2019 Category: Biochemistry Source Type: research

Cancer Stem Complex, Not a Cancer Stem Cell, Is the Driver of Cancer Evolution
AbstractHere, we put forward the hypothesis on the mechanism of functioning of cancer stem cells, provided that they exist. The hypothesis is based on the following postulates. 1) Paracrine exchange between cancer and stromal cells is efficient only if they are in a close contact and form a synapse-like cleft between them for the cell –cell crosstalk. The concentration of paracrine signaling molecules in the cleft is high because of the cleft small volume. 2) Cancer stem cellsper se do not exist. Instead, there are cancer stem complexes formed by cancer cells tightly bound to stromal cells (portable niches) that exch...
Source: Biochemistry (Moscow) - September 1, 2019 Category: Biochemistry Source Type: research

Comparison of State Transitions of the Photosynthetic Antennae in Arabidopsis and Barley Plants upon Illumination with Light of Various Intensity
AbstractChanges in the light energy distribution between the photosystems 1 and 2 (PS1 and PS2, respectively) due to the reversible migration of a part of the light-harvesting complex (LHC2) between the photosystems (state transitions, ST) have been studied in leaves of barley (Hordeum vulgare) andArabidopsis thaliana plants upon short-term illumination with light of various intensity that excited predominantly PS2. Changes in the ratio of fluorescence maxima at 745 and 685 nm in the low-temperature (77 K) fluorescence spectrum of chlorophylla (Chla) characterizing energy absorption by the PS1 and PS2, respectively, were i...
Source: Biochemistry (Moscow) - September 1, 2019 Category: Biochemistry Source Type: research

Photophysical Properties of Upconverting Nanoparticle –Phthalocyanine Complexes
AbstractInteraction between upconverting nanoparticles and aluminum octacarboxyphthalocyanine was studied. The efficiency of non-radiative energy transfer from the nanoparticles to phthalocyanine increased with the number of phthalocyanine molecules adsorbed on the nanoparticle, but only up to a certain limit. Further increase in the phthalocyanine concentration resulted in a decrease of its sensitized fluorescence due to the dimerization of dye molecules on the nanoparticle surface. When subjected to infrared irradiation, phthalocyanine molecules in the hybrid complex generated singlet oxygen. The observed effects are of ...
Source: Biochemistry (Moscow) - August 1, 2019 Category: Biochemistry Source Type: research

Role of TGF- β1 and C-Kit Mutations in the Development of Hepatocellular Carcinoma in Hepatitis C Virus-Infected Patients: in vitro Study
AbstractTransforming growth factor beta (TGF- β) acts as a tumor-suppressing cytokine in healthy tissues and non-malignant tumors. Yet, in malignancy, TGF-β can exert the opposite effects that can promote proliferation of cancer cells. C-Kit plays a prominent role in stem cell activation and liver regeneration after injury. However, little is known about the cross-talk between TGF-β and C-Kit and its role in the progression of hepatocellular carcinoma (HCC). Here, we studied the effect of increasing doses of TGF-β1 on CD44+CD90+ liver stem cells (LSCs) andC-Kit gene expression in malignant and adjacent ...
Source: Biochemistry (Moscow) - August 1, 2019 Category: Biochemistry Source Type: research

Comparison of the Size and Properties of the Cytochrome c /Cardiolipin Nanospheres in a Sediment and Non-polar Medium
AbstractApoptosis, as the major type of programmed cell death, plays an important role in the organism renewal and removal of defective and transformed cells, including cancer cells. One of the earliest apoptotic events is lipid peroxidation in the inner mitochondrial membrane catalyzed by a complex of cytochromec (CytC) with the mitochondrial phospholipid cardiolipin (CL). It was shown that mixing CytC and CL solutions results in the formation of CytC/CL complexes (Cyt-CL nanospheres) with a diameter of 11 –12 nm composed of the molten globule protein molecule and a CL monolayer. Using the methods of dynamic light s...
Source: Biochemistry (Moscow) - August 1, 2019 Category: Biochemistry Source Type: research

RNA (C5-cytosine) Methyltransferases
AbstractThe review summarizes the data on pro- and eukaryotic RNA (C5-cytosine) methyltransferases. The structure, intracellular location, RNA targets, and catalytic mechanisms of these enzymes, as well as the functional role of methylated cytosine residues in RNA are presented. The functions of RNA (C5-cytosine) methyltransferases unassociated with their methylation activity are discussed. Special attention is given to the similarities and differences in the structures and mechanisms of action of RNA and DNA methyltransferases. The data on the association of mutations in the RNA (C5-cytosine) methyltransferases genes and ...
Source: Biochemistry (Moscow) - August 1, 2019 Category: Biochemistry Source Type: research

Expression of mRNAs for IL-1 β, IL-6, IL-10, TNFα, CX3CL1, and TGFβ1 Cytokines in the Brain Tissues: Assessment of Contribution of Blood Cells with and without Perfusion
AbstractCytokines are important regulators of brain function under both normal and pathological conditions. Cytokines can be synthesized by resident cells of the central nervous system (CNS) (vascular endothelium, cells of the blood-brain barrier, parenchymal cells of the CNS) or cells in the lumen of blood vessels, as well as introduced with the bloodstream. The ratio between the quantity of cytokines synthesized in the CNS and those entering it from external sources under various conditions remains poorly understood. In this work, we studied the contribution of mRNAs from non-resident cells to the common pool of cytokine...
Source: Biochemistry (Moscow) - August 1, 2019 Category: Biochemistry Source Type: research

Analysis of Direct Effects of the CB1 Receptor Antagonist Rimonabant on Fatty Acid Oxidation and Glycogenolysis in Liver and Muscle Cells in vitro
AbstractRecent pharmacological findings regarding rimonabant, an anorectic and cannabinoid type 1 receptor (CB1R) antagonist, strongly suggest that some of its effects on the metabolic parameters and energy balance in rats are not related to the centrally mediated reduction in caloric intake. Instead, they may be associated with acute induction of glycogenolysis in the liver, in combination with transient increase in glucose oxidation and persistent increase in fat oxidation. It is possible that rimonabant produced direct shortor long-term stimulatory effect on these processes in primary and cultured rat cells. Rimonabant ...
Source: Biochemistry (Moscow) - August 1, 2019 Category: Biochemistry Source Type: research

Mechanisms of Non-coenzyme Action of Thiamine: Protein Targets and Medical Significance
AbstractThiamine (vitamin B1) is a precursor of the well-known coenzyme of central metabolic pathways thiamine diphosphate (ThDP). Highly intense glucose oxidation in the brain requires ThDP-dependent enzymes, which determines the critical significance of thiamine for neuronal functions. However, thiamine can also act through the non-coenzyme mechanisms. The well-known facilitation of acetylcholinergic neurotransmission upon the thiamine and acetylcholine co-release into the synaptic cleft has been supported by the discovery of thiamine triphosphate (ThTP)-dependent phosphorylation of the acetylcholine receptor-associated ...
Source: Biochemistry (Moscow) - August 1, 2019 Category: Biochemistry Source Type: research

RNA Editing by ADAR Adenosine Deaminases: From Molecular Plasticity of Neural Proteins to the Mechanisms of Human Cancer
AbstractRNA editing by adenosine deaminases of the ADAR family attracts a growing interest of researchers, both zoologists studying ecological and evolutionary plasticity of invertebrates and medical biochemists focusing on the mechanisms of cancer and other human diseases. These enzymes deaminate adenosine residues in the double-stranded (ds) regions of RNA with the formation of inosine. As a result, some RNAs change their three-dimensional structure and functions. Adenosine-to-inosine editing in the mRNA coding sequences may cause amino acid substitutions in the encoded proteins. Here, we reviewed current concepts on the...
Source: Biochemistry (Moscow) - August 1, 2019 Category: Biochemistry Source Type: research

Thermostable Lichenase from Clostridium thermocellum as a Host Protein in the Domain Insertion Approach
AbstractClostridium thermocellum lichenase (endo- β-1,3;1,4-glucan-D-glycosyl hydrolase, EC 3.2.1.73 (P29716)) has been tested for the insertion of two model fluorescent proteins (EGFP and TagRFP) into two regions of this enzyme. Functional folding of the resulting proteins was confirmed by retention of lichenase activity and EGFP and TagRFP fluor escence. These results convincingly demonstrate that (i) the two experimentally selected lichenase loop regions may serve as the areas for domain insertion without disturbing enzyme foldingin vivo; (ii) lichenase permits not only single but also tandem insertions of large pr...
Source: Biochemistry (Moscow) - August 1, 2019 Category: Biochemistry Source Type: research

Analysis of Protein Synthesis in Cucumber Leaves after Inoculation with Corynespora cassiicola : A Proteomic Approach
AbstractCucumber target leaf spot (TLS) disease caused byCorynespora cassiicola has become one of the most important fungal foliar diseases of cultivated cucumbers. However, the defense mechanisms of cucumber plants (Cucumis sativus) againstC. cassiicola are still poorly understood. Here, proteins from resistant cucumber plants were analyzed using iTRAQ (isobaric tags for relative and absolute quantification) method. A total of 286 differentially expressed proteins were identified (p 1.2 or
Source: Biochemistry (Moscow) - August 1, 2019 Category: Biochemistry Source Type: research

DNA Replication in Human Mitochondria
AbstractDNA replication in human mitochondria has been studied for several decades; however, its mechanism still remains unclear. During the last 15 years, many new experimental data on the mitochondrial replication have appeared, although extremely contradictory. Two asynchronous (strand displacement andRITOLS) and one synchronous (strand coupled) replication models have been proposed. In the asynchronous models, replication from the origin in the H-chain starts earlier, so that the replication of the two chains ends at different times. The synchronous model is more traditional and implies two replication forks with leadi...
Source: Biochemistry (Moscow) - August 1, 2019 Category: Biochemistry Source Type: research

The Role of Reverse Transcriptase in the Origin of Life
AbstractIt has been suggested that RNA polymerase ribozyme displaying reverse transcriptase and integrase activities has played a vital role in the origin of life on Earth. Here, we present a hypothesis that formation of universal ancestral units of all living organisms — retroelements — in the evolution was mediated by reverse transcriptase. The propensity of retroelements to mutations and their insertion capacity have formed a basis for the origin of complex DNA structures — primary genomes — that have given rise to archaea, eukaryotes, bacteria, and viru ses. Conserved properties of retroelements...
Source: Biochemistry (Moscow) - August 1, 2019 Category: Biochemistry Source Type: research

Advances and Challenges of Nanoparticle-Based Macrophage Reprogramming for Cancer Immunotherapy
AbstractDespite the progress of modern medicine, oncological diseases are still among the most common causes of death of adult populations in developed countries. The current therapeutic approaches are imperfect, and the high mortality of oncological patients under treatment, the lack of personalized strategies, and severe side effects arising as a result of treatment force seeking new approaches to therapy of malignant tumors. During the last decade, cancer immunotherapy, an approach that relies on activation of the host antitumor immune response, has been actively developing. Cancer immunotherapy is the most promising tr...
Source: Biochemistry (Moscow) - July 1, 2019 Category: Biochemistry Source Type: research

Carcinogenesis Associated with Human Papillomavirus Infection. Mechanisms and Potential for Immunotherapy
AbstractHuman papillomavirus (HPV) infection is responsible for approximately 5% of all cancers and is associated with 30% of all pathogen-related cancers. Cervical cancer is the third most common cancer in women worldwide; about 70% of cervical cancer cases are caused by the high-risk HPVs (HR HPVs) of genotypes 16 and 18. HPV infection occurs mainly through sexual contact; however, viral transmission via horizontal and vertical pathways is also possible. After HPV infection of basal keratinocytes or ecto-endocervical transition zone cells, viral DNA persists in the episomal form. In most cases, infected cells are elimina...
Source: Biochemistry (Moscow) - July 1, 2019 Category: Biochemistry Source Type: research

Cysteine Cathepsins: Potential Applications in Diagnostics and Therapy of Malignant Tumors
AbstractCysteine cathepsins are proteolytic enzymes involved in protein degradation in lysosomes and endosomes. Cysteine cathepsins have been also found in the tumor microenvironment during carcinogenesis, where they are implicated in proliferation, invasion and metastasis of tumor cells through the degradation of extracellular matrix, suppression of cell –cell interactions, and promotion of angiogenesis. In this regard, cathepsins can have a diagnostic value and represent promising targets for antitumor drugs aimed at inhibition of these proteases. Moreover, cysteine cathepsins can be used as activators of novel tar...
Source: Biochemistry (Moscow) - July 1, 2019 Category: Biochemistry Source Type: research

Immunotherapeutic Approaches for the Treatment of Colorectal Cancer
AbstractColorectal cancer (CRC) originating from the cells of the colon or rectum has a high mortality rate worldwide. Numerous attempts have been made to raise the overall survival rates of CRC patients. It is well-known that the development of malignant neoplasms is accompanied by suppression of the immune system, which is likely the cause for the failure of standard treatment methods. Immune response has long been an issue of great interest in cancer therapy and anti-tumor immunity that consider the development of immunotherapeutic antitumor methods resulting in the immune system activation as an important issue. This r...
Source: Biochemistry (Moscow) - July 1, 2019 Category: Biochemistry Source Type: research

MUC1 in Cancer Immunotherapy — New Hope or Phantom Menace?
AbstractUnderstanding of the functioning of MUC1 (human mucin) has advanced significantly over 40 years of its investigation. The anti-adhesive properties of the extracellular domain, which were the main focus of early studies initially explaining overexpression of MUC1 in progressing oncological diseases, were gradually put on the back burner. Researchers became more interested in its regulatory and signaling functions in cells rather in its anti-adhesive properties. The found the ability of MUC1 for signal transduction, and its ability to participate in cell metabolism opened new possibilities for improved control over c...
Source: Biochemistry (Moscow) - July 1, 2019 Category: Biochemistry Source Type: research

DNA Import into Plant Mitochondria: Complex Approach for in organello and in vivo Studies
The objective of this work was to improve and standardize the existing approaches for investigating DNA import into plant mitochondria in anin organello system. A method for detecting the import of fluorescently labeled DNA substrates has been developed. Based on the features of DNA import into the mitochondria, we suggested an efficient method for the evaluation of the DNA import efficiency by quantitative PCR. We also developed and characterized thein vivo system that allows to detect DNA transport from the cytoplasm to the mitochondrial matrix inArabidopsis thaliana protoplasts. A combination of the proposed techniques ...
Source: Biochemistry (Moscow) - July 1, 2019 Category: Biochemistry Source Type: research

T-Cell Engagers Based Bioassay for Evaluation of PD-1/PD-L1 Inhibitors Activity
In this study, we developed a cell-based bioassay for analyzing the activity of anti-PD-1 and anti-PD-L1 antibodies. We chose reporter system consisting of two cell lines and compared several approaches for activation of effector cell line based on superantigens, soluble anti-CD3 antibodies, transmembrane anti-CD3 antibodies, chimeric antigenic receptors (CARs) and bispecific T-cell engager antibodies. The bispecific T-cell engager antibodies offer several advantages over the other approaches. We characterized the bioassay and demonstrated its applicability for analyzing the activity of anti-PD-1 and anti-PD-L1 antibodies....
Source: Biochemistry (Moscow) - July 1, 2019 Category: Biochemistry Source Type: research

Intravasation as a Key Step in Cancer Metastasis
AbstractIntravasation is a key step in cancer metastasis during which tumor cells penetrate the vessel wall and enter circulation, thereby becoming circulating tumor cells and potential metastatic seeds. Understanding the molecular mechanisms of intravasation is critically important for the development of therapeutic strategies to prevent metastasis. In this article, we review current data on the mechanisms of cancer cell intravasation into the blood and lymphatic vessels. The entry of mature thymocytes into the circulation and of dendritic cells into the regional lymph nodes is considered as examples of intravasation unde...
Source: Biochemistry (Moscow) - July 1, 2019 Category: Biochemistry Source Type: research

Therapeutic Vaccines Against Human Papilloma Viruses: Achievements and Prospects
AbstractHuman papillomaviruses of high carcinogenic risk (HR HPVs) are major etiological agents of malignant diseases of the cervix, vulva, penis, anal canal, larynx, head, and neck. Prophylactic vaccination against HPV, which mainly covers girls and women under 25, does not prevent vertical and horizontal HPV transmission in infants and children and does not have a therapeutic effect. As a result, a significant proportion of the population is not protected from the HPV infection and development of HPV-associated neoplastic transformation and cancer, which indicates the need for development and intro- duction of therapeuti...
Source: Biochemistry (Moscow) - July 1, 2019 Category: Biochemistry Source Type: research

The Role of Checkpoint Inhibitors and Cytokines in Adoptive Cell-Based Cancer Immunotherapy with Genetically Modified T Cells
AbstractThis review focuses on the structure and molecular action mechanisms of chimeric antigen receptors (CARs) and major aspects of the manufacturing and clinical application of products for the CAR-T (CAR-modified T lymphocyte) therapy of hematological and solid tumors with special emphasis on the strategies for combined use of CAR-T therapy with immuno-oncological monoclonal antibodies (checkpoint inhibitors) and cytokines to boost survival, persistence, and anti-tumor efficacy of CAR-T therapy. The review also summarizes preclinical and clinical data on the additive effects of the combined use of CAR-T therapy with i...
Source: Biochemistry (Moscow) - July 1, 2019 Category: Biochemistry Source Type: research

Thematic Issue: Immuno-Oncology and Immunotherapy
AbstractCurrently, the use of immunotherapeutic approaches for creating new efficient therapeutic agents for cancer treatment is considered as one of the most promising areas in oncology. Despite significant advances in immuno-oncology during the recent years, some unresolved problems remain. The articles included in this thematic issue highlight the topical aspects of cancer immunotherapy by presenting different viewpoints of scientists, physicians, and drug developers. (Source: Biochemistry (Moscow))
Source: Biochemistry (Moscow) - July 1, 2019 Category: Biochemistry Source Type: research

A New Efficient Method for Production of Recombinant Antitumor Cytokine TRAIL and Its Receptor-Selective Variant DR5-B
AbstractThe cytokine TRAIL induces apoptosis in tumor cells of various origin without affecting normal cells. Clinical trials of TRAIL-receptor (DR4 and DR5) agonists (recombinant TRAIL or death receptors antibodies) have largely failed because most human tumors were resistant to them. Currently, a second generation of agents targeted at TRAIL-R with increased efficiency has been developed. To this end, we have developed DR5-B, a variant of TRAIL selectively interacting with DR5. We have developed a new efficient method for production of TRAIL and DR5-B using expression of these proteins inEscherichia coli strain SHuffle B...
Source: Biochemistry (Moscow) - June 1, 2019 Category: Biochemistry Source Type: research

The Opposite Effects of ROCK and Src Kinase Inhibitors on Susceptibility of Eukaryotic Cells to Invasion by Bacteria Serratia grimesii
AbstractBacterial internalization into eukaryotic cells is ensured by a sophisticated interplay of bacterial and host cell factors. Being a part of cell environment, opportunistic intracellular bacteria have developed various mechanisms providing their interaction with cell surface receptors (E-cadherin, integrins, epidermal growth factor receptor), activation of components of eukaryotic signaling pathways, and facilitation of bacterial uptake, survival, and intracellular replication. Our previous studies on the mechanisms underlying penetration of the opportunistic bacteriaSerratia grimesii into cultured eukaryotic cells ...
Source: Biochemistry (Moscow) - June 1, 2019 Category: Biochemistry Source Type: research

Myeloperoxidase-Induced Oxidation of Albumin and Ceruloplasmin: Role of Tyrosines
AbstractNeutrophil myeloperoxidase (MPO) plays an important role in protecting the body against infections. MPO products –hypohalous acids and phenoxyl radicals–are strong oxidants that can damage not only foreign intruders but also host tissues, including blood plasma proteins. Here, we compared the MPO-induced oxidation of two plasma proteins with antioxidant properties–human serum albumin (HSA) and ceruloplas min (CP). Incubation of both proteins with hypochlorite (NaOCl) or catalytically active MPO (MPO + H2O2), which synthesizes hypochlorous acid (HOCl) in the presence of chloride ions, resulted in t...
Source: Biochemistry (Moscow) - June 1, 2019 Category: Biochemistry Source Type: research

Resveratrol Promotes in vitro Differentiation of Osteoblastic MC3T3-E1 Cells via Potentiation of the Calcineurin/NFATc1 Signaling Pathway
AbstractResveratrol has been shown to stimulate differentiation of osteoblastic MC3T3-E1 cellsin vitro; however, the mechanisms underlying the anabolic effect of resveratrol on osteoblasts remain largely unknown. Our study was aimed to investigate the molecular mechanism of resveratrol-induced differentiation of MC3T3-E1 cells. MC3T3-E1 cells were treated for 8 days with different concentrations of resveratrol (10−8-10−6 M) and 10−6 M cyclosporine A (CsA), a specific inhibitor of the calcineurin/NFAT pathway. According to the results of pilot studies of cell proliferation and alkaline phos-phatase activit...
Source: Biochemistry (Moscow) - June 1, 2019 Category: Biochemistry Source Type: research