Termination Mechanism Research Articles

P53/miR-34a/SIRT1 positive feedback loop regulates the termination of liver regeneration.

The capacity of the liver to restore its architecture and function assures good prognoses of patients who suffer serious hepatic injury, cancer resection, or living donor liver transplantation. Only a few studies have shed light on the mechanisms involved in the termination stage of LR. Here, we attempt to further verify the role of the p53/miR-34a/SIRT1 positive feedback loop in the termination of liver regeneration and its possible relationship with liver cancer. We performed partial hepatectomy (PH) in mice transfected with adenovirus (Ade) overexpressing P53 and adenovirus-associated virus (AAV) overexpressing miR-34a. LR was analyzed by liver weight/body weight, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and cell proliferation, and the related cellular signals were investigated. Bile acid (BA) levels during LR were analyzed by metabolomics of bile acids. We found that the P53/miR-34a/SIRT1 positive feedback loop was activated in the late phase of LR. Overexpression of P53 or miR-34a terminated LR early and enhanced P53/miR-34a/SIRT1 positive feedback loop expression and its proapoptotic effect. T-β-MCA increased gradually during LR and peaked at 7 days after PH. T-β-MCA inhibited cell proliferation and promoted cell apoptosis via facilitating the P53/miR-34a/SIRT1 positive feedback loop during LR by suppressing FXR/SHP. The P53/miR-34a/SIRT1 positive feedback loop was abolished in HCC patients with P53 mutations. The P53/miR-34a/SIRT1 positive feedback loop plays an important role in the termination of LR. Our findings showed the molecular and metabolic mechanisms of LR termination and provide a potential therapeutic alternative for treating P53-wild-type HCC patients.

Optogenetic termination of atrial tachyarrhythmias by brief pulsed light stimulation

AimsThe most efficient way to acutely restore sinus rhythm from atrial fibrillation (AF) is electrical cardioversion, which is painful without adequate sedation. Recent studies in various experimental models have indicated that optogenetic termination of AF using light-gated ion channels may provide a myocardium-specific and potentially painless alternative future therapy. However, its underlying mechanism(s) remain(s) incompletely understood. As brief pulsed light stimulation, even without global illumination, can achieve optogenetic AF termination, besides direct conduction block also modulation of action potential (AP) properties may be involved in the termination mechanism. We studied the relationship between optogenetic AP duration (APD) and effective refractory period (ERP) prolongation by brief pulsed light stimulation and termination of atrial tachyarrhythmia (AT). Methods and resultsHearts from transgenic mice expressing the H134R variant of channelrhodopsin-2 in atrial myocytes were explanted and perfused retrogradely. AT induced by electrical stimulation was terminated by brief pulsed blue light stimulation (470 nm, 10 ms, 16 mW/mm2) with 68% efficacy. The termination rate was dependent on pulse duration and light intensity. Optogenetically imposed APD and ERP changes were systematically examined and optically monitored. Brief pulsed light stimulation (10 ms, 6 mW/mm2) consistently prolonged APD and ERP when light was applied at different phases of the cardiac action potential. Optical tracing showed light-induced APD prolongation during the termination of AT. ConclusionOur results directly demonstrate that cationic channelrhodopsin activation by brief pulsed light stimulation prolongs the atrial refractory period suggesting that this is one of the key mechanisms of optogenetic termination of AT.

Unique Initiation and Termination Mechanisms Involved in the Biosynthesis of a Hybrid Polyketide-Nonribosomal Peptide Lyngbyapeptin B Produced by the Marine Cyanobacterium Moorena bouillonii.

Lyngbyapeptin B is a hybrid polyketide-nonribosomal peptide isolated from particular marine cyanobacteria. In this report, we carried out genome sequence analysis of a producer cyanobacterium Moorena bouillonii to understand the biosynthetic mechanisms that generate the unique structural features of lyngbyapeptin B, including the (E)-3-methoxy-2-butenoyl starter unit and the C-terminal thiazole moiety. We identified a putative lyngbyapeptin B biosynthetic (lynB) gene cluster comprising nine open reading frames that include two polyketide synthases (PKSs: LynB1 and LynB2), four nonribosomal peptide synthetases (NRPSs: LynB3, LynB4, LynB5, and LynB6), a putative nonheme diiron oxygenase (LynB7), a type II thioesterase (LynB8), and a hypothetical protein (LynB9). In vitro enzymatic analysis of LynB2 with methyltransferase (MT) and acyl carrier protein (ACP) domains revealed that the LynB2 MT domain (LynB2-MT) catalyzes O-methylation of the acetoacetyl-LynB2 ACP domain (LynB2-ACP) to yield (E)-3-methoxy-2-butenoyl-LynB2-ACP. In addition, in vitro enzymatic analysis of LynB7 revealed that LynB7 catalyzes the oxidative decarboxylation of (4R)-2-methyl-2-thiazoline-4-carboxylic acid to yield 2-methylthiazole in the presence of Fe2+ and molecular oxygen. This result indicates that LynB7 is responsible for the last post-NRPS modification to give the C-terminal thiazole moiety in lyngbyapeptin B biosynthesis. Overall, we identified and characterized a new marine cyanobacterial hybrid PKS-NRPS biosynthetic gene cluster for lyngbyapeptin B production, revealing two unique enzymatic logics.

Head-on and co-directional RNA polymerase collisions orchestrate bidirectional transcription termination

Genomic DNA is a crowded track where motor proteins frequently collide. It remains underexplored whether these collisions carry physiological function. In this work, we develop a single-molecule assay to visualize the trafficking of individual E.coli RNA polymerases (RNAPs) on DNA. Based on transcriptomic data, we hypothesize that RNAP collisions drive bidirectional transcription termination of convergent gene pairs. Single-molecule results show that the head-on collision between two converging RNAPs is necessary to prevent transcriptional readthrough but insufficient to release the RNAPs from the DNA. Remarkably, co-directional collision of a trailing RNAP into the head-on collided complex dramatically increases the termination efficiency. Furthermore, stem-loop structures formed in the nascent RNA are required for collisions to occur at well-defined positions between convergent genes. These findings suggest that physical collisions between RNAPs furnish a mechanism for transcription termination and that programmed genomic conflicts can be exploited to co-regulate the expression of multiple genes.

Rho-dependent transcription termination is the dominant mechanism in Mycobacterium tuberculosis

Intrinsic and Rho-dependent transcription termination mechanisms regulate gene expression and recycle RNA polymerase in bacteria. Both the modes are well studied in Escherichia coli, and a few other organisms. The understanding of Rho function is limited in most other bacteria including mycobacteria. Here, we highlight the dominance of Rho-dependent termination in mycobacteria and validate Rho as a key regulatory factor. The lower abundance of intrinsic terminators, high cellular levels of Rho, and its genome-wide association with a majority of transcriptionally active genes indicate the pronounced role of Rho-mediated termination in Mycobacterium tuberculosis (Mtb). Rho modulates the termination of RNA synthesis for both protein-coding and stable RNA genes in Mtb. Concordantly, the depletion of Rho in mycobacteria impact its growth and enhances the transcription read-through at 3′ ends of the transcription units. We demonstrate that MtbRho is catalytically active in the presence of RNA with varied secondary structures. These properties suggest an evolutionary adaptation of Rho as the efficient and preponderant mode of transcription termination in mycobacteria.

A unified hypothesis of SUDEP: Seizure-induced respiratory depression induced by adenosine may lead to SUDEP but can be prevented by autoresuscitation and other restorative respiratory response mechanisms mediated by the action of serotonin on the periaqueductal gray.

Sudden unexpected death in epilepsy (SUDEP) is a major cause of death in people with epilepsy (PWE). Postictal apnea leading to cardiac arrest is the most common sequence of terminal events in witnessed cases of SUDEP, and postconvulsive central apnea has been proposed as a potential biomarker of SUDEP susceptibility. Research in SUDEP animal models has led to the serotonin and adenosine hypotheses of SUDEP. These neurotransmitters influence respiration, seizures, and lethality in animal models of SUDEP, and are implicated in human SUDEP cases. Adenosine released during seizures is proposed to be an important seizure termination mechanism. However, adenosine also depresses respiration, and this effect is mediated, in part, by inhibition of neuronal activity in subcortical structures that modulate respiration, including the periaqueductal gray (PAG). Drugs that enhance the action of adenosine increase postictal death in SUDEP models. Serotonin is also released during seizures, but enhances respiration in response to an elevated carbon dioxide level, which often occurs postictally. This effect of serotonin can potentially compensate, in part, for the adenosine-mediated respiratory depression, acting to facilitate autoresuscitation and other restorative respiratory response mechanisms. A number of drugs that enhance the action of serotonin prevent postictal death in several SUDEP models and reduce postictal respiratory depression in PWE. This effect of serotonergic drugs may be mediated, in part, by actions on brainstem sites that modulate respiration, including the PAG. Enhanced activity in the PAG increases respiration in response to hypoxia and other exigent conditions and can be activated by electrical stimulation. Thus, we propose the unifying hypothesis that seizure-induced adenosine release leads to respiratory depression. This can be reversed by serotonergic action on autoresuscitation and other restorative respiratory responses acting, in part, via the PAG. Therefore, we hypothesize that serotonergic or direct activation of this brainstem site may be a useful approach for SUDEP prevention.

Efficient systematic turbo polar decoding based on optimized scaling factor and early termination mechanism

In this paper, an efficient early termination (ET) mechanism for systematic turbo-polar code (STPC) based on optimal estimation of scaling factor (SF) is proposed. The gradient of the regression line which best fits the distance between a priori and extrinsic information is used to estimate the SF. The multiplication of the extrinsic information by the proposed SF presents effectiveness in resolving the correlation issue between intrinsic and extrinsic reliability information traded between the two typical parallel concatenated soft-cancellation (SCAN) decoders. It is shown that the SF has improved the conventional STPC by about 0.3 dB with an interleaver length of 64 bits, and about 1 dB over the systematic polar code (SPC) at a bit error rate (BER) of . A new scheme is proposed as a stopping criterion, which is mainly based on the estimated value of SF at the second component decoder and the decoded frozen bits for each decoding iteration. It is shown that the proposed ET results in halving the average number of iterations (ANI) without adding considerable complexity. Moreover, the modified codes present comparable results in terms of BER to the codes that utilize fix number of iterations.

RTEL1 and MCM10 overcome topological stress during vertebrate replication termination.

Topological stress can cause converging replication forks to stall during termination of vertebrate DNA synthesis. However, replication forks ultimately overcome fork stalling, suggesting that alternative mechanisms of termination exist. Using proteomics in Xenopus egg extracts, we show that the helicase RTEL1 and the replisome protein MCM10 are highly enriched on chromatin during fork convergence and are crucially important for fork convergence under conditions of topological stress. RTEL1 and MCM10 cooperate to promote fork convergence and do not impact topoisomerase activity but do promote fork progression through a replication barrier. Thus, RTEL1 and MCM10 play a general role in promoting progression of stalled forks, including when forks stall during termination. Our data reveal an alternate mechanism of termination involving RTEL1 and MCM10 that can be used to complete DNA synthesis under conditions of topological stress.

Structural basis for intrinsic transcription termination.

Efficient and accurate termination is required for gene transcription in all living organisms1,2. Cellular RNA polymerases in both bacteria and eukaryotes can terminate their transcription through a factor-independent termination pathway3,4-called intrinsic termination transcription in bacteria-in which RNA polymerase recognizes terminator sequences, stops nucleotide addition and releases nascent RNA spontaneously. Here we report a set of single-particle cryo-electron microscopy structures of Escherichia coli transcription intrinsic termination complexes representing key intermediate states of the event. The structures show how RNA polymerase pauses at terminator sequences, how the terminator RNA hairpin folds inside RNA polymerase, and how RNA polymerase rewinds the transcription bubble to release RNA and then DNA. These macromolecular snapshots define a structural mechanism for bacterial intrinsic termination and a pathway for RNA release and DNA collapse that isrelevant for factor-independent termination by all RNA polymerases.

Mechanism of Sen1 translocation

Transcription termination is a critical step for gene regulation and genome integrity among all kingdoms of life. In <i>Saccharomyces cerevisiae</i>, one of the major termination pathways is accomplished by Sen1 helicase, a homolog to human Senataxin (SETX), defection of which raises the diseases for the central nervus system of human. Although it has been proposed that Sen1 translocates along nucleic acids by consuming adenosine triphosphates (ATPs) during termination, the mechanism for this translocation activity of Sen1 has not been well understood. In this work, our aim is to investigate the mechanism of Sen1 translocation by measuring the interactions between Sen1 and different types of nucleic acids by polyacrylamide gel electrophoresis (PAGE) assay or single-molecule Fӧrster resonance energy transfer (FRET) assay. We firstly observe the unwinding activity of Sen1 on a tailed duplex DNA in the presence of 1 mM ATP via PAGE assay, where the translocation activity of Sen1 is involved. As the binding activity is crucial for translocation, then we examine the binding affinity of Sen1 to the single-stranded DNA via PAGE assay, revealing a stable binding of Sen1 with an occupied length of nucleic acids of less than 24 nt. In the presence of 1 µM ATP, we observe that Sen1 dynamically binds to and dissociates from the tailed duplex DNA in the single-molecule FRET assay. By titrating ATP concentrations from 1–500 µM, we observe a gradual decrease in the mean durations of Sen1 binding, suggesting an ATP-dependent binding affinity of Sen1 to single-stranded DNA. We then fit these mean durations to the classical Michaelis-Menten model and obtain a minimum binding duration of (0.18 ± 0.01) s at saturating ATP concentrations and <i>K</i><sub>m</sub> of (13.1 ± 0.1) µM for the ATP-dependent binding of Sen1. This result is consistent with that from a translocation activity of Sen1. Taking into account the translocation length of the half of the single-stranded tail, i.e. 13 nt, a mean rate of 70 nt/s is estimated. Reversing the translocation direction, we observe an increase in the duration of Sen1 binding to the single-stranded tail, which suggests an impediment of DNA duplex in front of Sen1 translocation or the possible duplex DNA unwinding activity of Sen1. Our quantitative measurements on Sen1 translocation are helpful in deepening our understanding of the mechanism of eukaryotic transcription termination by Sen1.

Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106

The antiviral pseudo-base T705 and its de-fluoro analog T1106 mimic adenine or guanine and can be competitively incorporated into nascent RNA by viral RNA-dependent RNA polymerases. Although dispersed, single pseudo-base incorporation is mutagenic, consecutive incorporation causes polymerase stalling and chain termination. Using a template encoding single and then consecutive T1106 incorporation four nucleotides later, we obtained a cryogenic electron microscopy structure of stalled influenza A/H7N9 polymerase. This shows that the entire product-template duplex backtracks by 5 nt, bringing the singly incorporated T1106 to the+1 position, where it forms an unexpected T1106:U wobble base pair. Similar structures show that influenza B polymerase also backtracks after consecutive T1106 incorporation, regardless of whether prior single incorporation has occurred. These results give insight into the unusual mechanism of chain termination by pyrazinecarboxamide base analogs. Consecutive incorporation destabilizes the proximal end of the product-template duplex, promoting irreversible backtracking to a more energetically favorable overall configuration.

Experimental study on the effects of local sediment accumulation on a debris flow surge in a steep channel

Debris flow surges can terminate in a steep channel of > 15°. However, the termination process and mechanisms remain unknown. This study conducted small-scale flume experiments to investigate the effects of local sediment accumulation on debris-flow surges in a steep channel. The experiments demonstrated that local accumulation of bed sediment terminates a debris flow surge owing to abrupt changes in bed gradients and infiltration of debris flow interstitial water. Subsequently, the mass of the terminated debris-flow surge and bed sediment began to move, triggering a larger debris-flow surge. This result suggests that predicting the scale of a debris flow arriving downstream requires measuring the distribution of bed sediment in the debris flow initiation zone.

Raspuštanje parlamenta prema Ustavu Republike Srbije od 2006. godine - neka otvorena pitanja

This article covers four parts. In the first part of the paper, they are explained in the most important paragraphs of the powers to dissolve the parliament in order to form the basic theoretical framework of this constitutional mechanism of termination of the mandate of the parliament before the expiry of the mandate of its members, with special reference to its legal regulations in the Republic of Serbia. In the following parts of the paper, based on the previously established theoretical frameworks of the mechanism of dissolution of the parliament, it was pointed out the legal nature of the dissolved parliament and its limitations, and then discussed some open issues relating to the dissolved parliament in the Constitution of the Republic of Serbia since 2006 in order to give our opinion on the reasons for the dissolution of the parliament and what are the ongoing and urgent tasks that the dissolved parliament performs, what should be more clearly defined in some future revision of the constitution and laws in order to avoid in practice different interpretations and misinterpretations.

LEGAL PROBLEMATICS OF CREDIT SETTLEMENT IN INDONESIAN BANKING CRIME

Based on Article 37D of the Law of the Republic of Indonesia Number 4 of 2023 Concerning the Development and Strengthening of the Financial Sector (UUPPSK), OJK can stop investigations into alleged tipibanks. The termination of the investigation is contrary to the terms of termination of the investigation as specified in Article 109 of the Criminal Procedure Code which states that a crime can only be stopped if there is insufficient evidence, the case is not a criminal case and is due to legal interests and Article 1 of the Criminal Code regarding the principle of legality. Tipibank termination conditions are; there is a request from the perpetrator of the suspected bank crime against which the OJK approves and the perpetrator pays all losses and costs incurred as a result of the banking crime. there is a request from the suspected perpetrator of bank fraud that is given to OJK and OJK accepts and approves the said application, whether or not there is settlement of losses arising from tipibank, the amount of the loss and the impact on the banking sector, banks, the interests of customers and/or society. Meanwhile, the investigation termination mechanism is; the application of the alleged perpetrator of the tipibank was approved by the OJK and the perpetrator of the alleged tipibank paid compensation. Some of the problems in solving the alleged bank crime by stopping the investigation include; The condition for terminating a tipibank investigation is contrary to the Criminal Procedure Code and the Criminal Code, the concept of resolving allegations of tipibank through termination of investigation is not in line with the principles of restorative justice and the concept of settlement out of court (mediation). Typical bank generalizations that can be resolved through termination of investigations can eliminate the function and purpose of law. Ambiguity regarding the meaning of violations and bank tipi in the UUPPSK and PP-UUPPSK can cause its own problems in its application.

Rapidly achieving a reliable full-ceramic interface of ZrC-SiC composite using Ti interlayer via pulsed electric current joining

A reliable full-ceramic interface of ZrC-SiC composite was achieved rapidly at low temperature via pulsed electric current joining. Using a Ti foil as joining interlayer, the Zr and Si atoms reacted with Ti to form Ti3Zr3Si3, while the dissolved C precipitated in form of TiC. The current delivering during joining promoted the atomic diffusion and caused the preferential growth of TiC, rapidly achieving a full-ceramic interface at 1300 ℃. Evaluating the reliability by Weibull distribution, the full-ceramic interface exhibited a considerable characteristic strength of 178 MPa, and its reliability was better than the raw ZrC-SiC composite. The in-situ formed ceramic interface toughened the joint via the mechanism of multi-cracking, crack deflection and termination. The proposed method provides a practical technology for the rapid joining of ultra-high temperature composites or the construction of layered composites with high toughness at low temperature.

Tuning the Magnetic Properties of Cr2TiC2Tx through Surface Terminations: A Theoretical Study.

Recently, magnetic two-dimensional Cr2TiC2Tx MXenes with promising applications in spin electronics have been experimentally confirmed. However, the underlying magnetic mechanism needs to be further investigated. Along these lines, in this work, the magnetic properties of Cr2TiC2On/4F2-n/4 and Cr2TiC2On/4 structures were simulated through first-principle calculations using the GGA+U approach. The values of 4.1 and 3.1 eV were calculated for the Hubbard U of Cr and Ti, respectively, by applying the linear response method. Interestingly, the Cr2TiC2On/4F2-n/4-based configurations with low O content (n ≤ 4) exhibit antiferromagnetic behavior, while the majority of the respective configurations with high O content (n ≥ 5) are ferromagnetic. As far as the Cr2TiC2O5/4F3/4 structure (n = 5) is concerned, the value of about 2.64 μB was estimated for the magnetic moment of the Cr atom. On top of that, the Curie temperature lies within the range of 10~47 K. The extracted theoretical results are in good agreement with experimental outcomes of the Cr2TiC2O1.3F0.8-based structure. From the simulated results, it can be also argued that the magnetic moment of Cr atoms and the Neel temperature can be directly tuned by the active content of O atoms. The conductivity of both Cr2TiC2On/4F2-n/4 and Cr2TiC2On/4 configurations can be regulated by the externally applied magnetic field, while the density of states around the Fermi level shifted significantly between ferromagnetic and antiferromagnetic arrangements. The acquired results provide important theoretical insights to tuning the magnetic properties of Cr2TiC2Tx-based structures through surface termination mechanisms, which are quite significant for their potential applications in spin electronics.

Early Termination Mechanism of Public–Private Partnership Transportation Projects with Government Guarantee

Early Termination Mechanism of Public–Private Partnership Transportation Projects with Government Guarantee

Double antiglutamatergic treatment in patients with status epilepticus: A case series

IntroductionStatus epilepticus (SE) continues to be a challenging neurological emergency with high morbidity and mortality. During treatment, different regimens are practiced encompassing all known seizure termination mechanisms. To our knowledge, this is the first case series report describing EEG patterns and clinical outcomes in patients treated with ketamine and perampanel (PER) concomitantly. ObjectiveTo assess clinical and electrographic outcomes in patients receiving dual antiglutamatergic therapy in SE. ResultsTwenty-one out of twenty five patients were treated with ketamine, and four patients with ketamine were associated with PER. In the ketamine plus PER group, three out of four patients had convulsive SE, and one had non-convulsive status epilepticus (NCSE), whereas eight patients in the ketamine group had NCSE. The incidence of beta pattern appearance on EEG after starting patients on ketamine and PER was achieved in all four patients (100%) compared to (61.9%) in the other group. A burst suppression pattern was recorded in 75% of patients treated with ketamine and PER, in comparison to 28.5% of patients in patients treated with a different regimen. The time to resolution of SE was significantly shorter in the ketamine group (median 24 (24–64) h vs. 6 (05–144) h p > 0.05). Moreover, the average number of days on IV anesthetic was slightly lower in a patient treated with PER concomitantly. In terms of morbidity, the average increase in mRS was also lower in the ketamine and PER group, although it was not statistically significant. ConclusionsDual anti-glutamatergic therapy could provide a favorable approach to treating SE, which yet needs to be further investigated through larger randomized control studies.

Glycolysis regulates neuronal excitability via lactate receptor, HCA1R.

Repetitively firing neurons during seizures accelerate glycolysis to meet energy demand, which leads to the accumulation of extracellular glycolytic by-product lactate. Here, we demonstrate that lactate rapidly modulates neuronal excitability in times of metabolic stress via the hydroxycarboxylic acid receptor type 1 (HCA1R) to modify seizure activity. The extracellular lactate concentration, measured by a biosensor, rose quickly during brief and prolonged seizures. In two epilepsy models, mice lacking HCA1R (lactate receptor) were more susceptible to developing seizures. Moreover, HCA1R deficient (knockout) mice developed longer and more severe seizures than wild-type littermates. Lactate perfusion decreased tonic and phasic activity of CA1 pyramidal neurons in genetically encoded calcium indicator 7 imaging experiments. HCA1R agonist 3-chloro-5-hydroxybenzoic acid (3CL-HBA) reduced the activity of CA1 neurons in HCA1R WT but not in knockout mice. In patch-clamp recordings, both lactate and 3CL-HBA hyperpolarized CA1 pyramidal neurons. HCA1R activation reduced the spontaneous excitatory postsynaptic current frequency and altered the paired-pulse ratio of evoked excitatory postsynaptic currents in HCA1R wild-type but not in knockout mice, suggesting it diminished presynaptic release of excitatory neurotransmitters. Overall, our studies demonstrate that excessive neuronal activity accelerates glycolysis to generate lactate, which translocates to the extracellular space to slow neuronal firing and inhibit excitatory transmission via HCA1R. These studies may identify novel anticonvulsant target and seizure termination mechanisms.

Structural, functional, and molecular mechanisms of endometrial transformation in habitual pregnancy failure

Introduction. Habitual pregnancy failure (HPF) has long been a pressing problem of modern medicine and is characterized by multiple pathogenetic mechanisms of early pregnancy termination. The aim of the study was to examine the expression of estrogen, progesterone, progesterone-induced blocking factor and stromal cell factor-1 receptors in endometrial biopsy specimens from patients with HPF. Materials and methods. Histological and immunohistochemical studies were performed on 75 endometrial biopsies: 50 endometrial biopsies were taken from patients with HPF and chronic endometritis with no more than three pregnancies, and 25 endometrial biopsies were taken from conditionally healthy patients. Endometrial biopsy was performed on days 19 to 22 of the menstrual cycle. Histological examination of endometrial biopsy specimens was performed according to the standard technique with hematoxylin and eosin staining. The expression of estrogen receptor (ER), progesterone receptor (PR), progesterone-induced blocking factor (anti-PIBF), and stromal cell factor-1 (anti- SDF-1) was assessed by immunohistochemistry. Results. In patients with HPF, the endometrium corresponded to the middle stage of the secretion phase in 32 % of cases. Immunohistochemical study in patients with HPF verified multifocal decrease of estrogen and progesterone receptor expression in the stromal component in 82 % of cases. Assessment of PIBF and SDF-1 expression in the glands and stroma of the endometrial mid-stage secretion phase in patients with HPF revealed a statistically significant decrease compared to the control group. Discussion. The presence of chronic endometritis in patients with HPF leads to impaired endometrial secretory transformation, decreased expression of estrogen and progesterone receptors in the endometrial stroma, and decreased expression of PIBF and SDF-1 in the glands and endometrial stroma. The results of the study suggest the need for pathogenetic therapy of chronic endometritis and pregravidarial preparation in patients with HPF. Conclusion. Regardless of the completeness of endometrial transformation, desynchronosis of the receptor profile, altered expression of immunological markers (PIBF and SDF-1) against the background of chronic endometritis, and structural and molecular disturbances serve as factors of early pregnancy loss.