[Molecular Ion Channel Blockers of Influenza A and SARS-CoV-2 Viruses].

Molecules were proposed to block the functional cycles of the influenza virus A and SARS-CoV- 2. The blocker molecules efficiently bind inside the M2 and E channels of influenza A and SARS-CoV-2 viruses and block diffusion of H^(+)/K^(+) ions, thus distorting the virus functional cycle. A family of positively charged (+2 e.

Thermodynamic parameters obtained for the formation of the Cas12a-RNA/DNA complex.

The thermodynamics of interactions between Cas12a, RNA, and DNA are important to understanding the molecular mechanisms governing CRISPR-Cas12a's specificity and function. In this study, we employed isothermal titration calorimetry (ITC) and molecular dynamics (MD) simulations to investigate the binding properties and energetic contributions of Cas12a-crRNA complexes with single-stranded (ssDNA) and double-stranded (dsDNA) DNA substrates. ITC analyses revealed significant thermal effects during the interaction of Cas12a-crRNA with ssDNA but no detectable effects with dsDNA.

[Ossification of the gum over intraosseal implant].

In a patient after implantation of a metal screw implant into the bone with suturing of the soft tissues above it after 6 months there was a spontaneous delimitation of the product by a thin strip of compact bone tissue, most likely formed from the bone structures damaged during the operation. Small bone fragments formed during the preparation of the implantation bed were found in the tissues as homogeneous eosinophilic deposits without inflammation and macrophage reactions.

[Endometrial adenocarcinoma with mutations in POLE, TP53 genes and microsatellite instability].

The molecular classification of endometrial cancer developed by The Cancer Genome Atlas project (TCGA, 2013) is currently actively used in gynecological oncology. According to it, endometrial carcinoma is divided into four molecular subtypes: -mutated, MMR deficient (dMMR), -aberrant and unspecified. Endometrial cancer samples belonging to the dMMR and -mutant types are characterized by specific genetic profiles reflecting the hyper- and ultramutant phenotypes of the tumor.

Generation of Isogenic iPSC Lines for Studying the Effect of the p.N515del (c.1543_1545delAAC) Variant on MYBPC3 Function and Hypertrophic Cardiomyopathy Pathogenesis.

The clinical significance of numerous cardiovascular gene variants remains to be determined. CRISPR/Cas9 allows for the introduction and/or correction of a certain variant in induced pluripotent stem cells (iPSCs). The resulting isogenic iPSC lines can be differentiated into cardiomyocytes and used as a platform to assess the pathogenicity of the variant.

Aminomethylmorpholino Nucleosides as Novel Inhibitors of PARP1 and PARP2: Experimental and Molecular Modeling Analyses of Their Selectivity and Mechanism of Action.

Poly(ADP-ribose) polymerases 1 and 2 (PARP1 and PARP2) play a key role in DNA repair. As major sensors of DNA damage, they are activated to produce poly(ADP-ribose). PARP1/PARP2 inhibitors have emerged as effective drugs for the treatment of cancers with BRCA deficiencies.

The Photomodification Method Allows for Determining the Composition of the Full and Soft Protein Corona on the Lipid Surface of Composite Nanoparticles.

A protein corona (PC) is formed and maintained on the surface of any nanoparticle (NP) introduced into biological media. The full PC is formed by a hard and soft corona, and the latter determines the nature of the interaction of NPs with cells and the body's liquids. Nanomedicines are becoming increasingly important in modern health services, making information about the composition of PCs on the surface of NPs critically important for "managing" the behavior of nano-objects in the body.

Using Computer Modeling and Experimental Methods to Screen for Aptamers That Bind to the VV-GMCSF-LACT Virus.

Oncolytic virotherapy is a promising approach for cancer treatment. However, when introduced into the body, the virus provokes the production of virus-neutralizing antibodies, which can reduce its antitumor effect. To shield viruses from the immune system, aptamers that can cover the membrane of the viral particle are used.

Amphiphilic Oligonucleotide Derivatives-Promising Tools for Therapeutics.

Recent advances in genetics and nucleic acid chemistry have created fundamentally new tools, both for practical applications in therapy and diagnostics and for fundamental genome editing tasks. Nucleic acid-based therapeutic agents offer a distinct advantage of selectively targeting the underlying cause of the disease. Nevertheless, despite the success achieved thus far, there remain unresolved issues regarding the improvement of the pharmacokinetic properties of therapeutic nucleic acids while preserving their biological activity.

Phase Separation of FUS with Poly(ADP-ribosyl)ated PARP1 Is Controlled by Polyamines, Divalent Metal Cations, and Poly(ADP-ribose) Structure.

Fused in sarcoma (FUS) is involved in the formation of nuclear biomolecular condensates associated with poly(ADP-ribose) [PAR] synthesis catalyzed by a DNA damage sensor such as PARP1. Here, we studied FUS microphase separation induced by poly(ADP-ribosyl)ated PARP1 [PAR-PARP1] or its catalytic variants PARP1 and PARP1, respectively, synthesizing (short PAR)-PARP1 or (short hyperbranched PAR)-PARP1 using dynamic light scattering, fluorescence microscopy, turbidity assays, and atomic force microscopy. We observed that biologically relevant cations such as Mg, Ca, or Mn or polyamines (spermine or spermidine) were essential for the assembly of FUS with PAR-PARP1 and FUS with PAR-PARP1 in vitro.

Photocleavable Guide crRNAs for a Light-Controllable CRISPR/Cas9 System.

The design of controllable and precise RNA-targeted CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats) systems is an important problem of modern molecular biology and genetic technology. Herein, we have designed a series of photocleavable guide CRISPR RNAs (crRNA) and their 2'-modified (2'-fluoro and locked nucleic acid) analogs containing one or two 1-(2-nitrophenyl)-1,2-ethanediol photolabile linkers (PL). We have demonstrated that these crRNAs can be destroyed by relatively mild UVA irradiation with the rate constants 0.

The Trajectory of Damaged-Base Eversion into the Active Site of Apurinic/Apyrimidinic Endonuclease APE1 Regulates This Enzyme's Substrate Specificity.

Apurinic/apyrimidinic endonuclease 1 (APE1) is responsible for the hydrolysis of the phosphodiester bond on the 5' side of an apurinic/apyrimidinic site during base excision repair. Moreover, in DNA, this enzyme can recognize nucleotides containing such damaged bases as 5,6-dihydro-2'-deoxyuridine (DHU), 2'-deoxyuridine (dU), alpha-2'-deoxyadenosine (αA), and 1,6-ethenoadenosine (εA). Previously, by pulsed electron-electron double resonance spectroscopy and pre-steady-state kinetic analysis, we have revealed multistep DNA rearrangements during the formation of the catalytic complex.

Kinetic Features of Degradation of R-Loops by RNase H1 from .

R-loops can act as replication fork barriers, creating transcription-replication collisions and inducing replication stress by arresting DNA synthesis, thereby possibly causing aberrant processing and the formation of DNA strand breaks. RNase H1 (RH1) is one of the enzymes that participates in R-loop degradation by cleaving the RNA strand within a hybrid RNA-DNA duplex. In this study, the kinetic features of the interaction of RH1 from with R-loops of various structures were investigated.

Novel DNA Aptamers to Dickkopf-1 Protein and Their Application in Colorimetric Sandwich Assays for Target Detection in Patients with Axial Spondyloarthritis.

Chronic immunoinflammatory rheumatic diseases, such as axial spondyloarthritis (AxSpA), are accompanied by a dysregulation of bone remodeling. Among potential biomarkers of bone metabolism, the Wnt pathway antagonist, Dickkopf-1 (DKK-1), is of particular interest because of its potential to reflect a shift towards joint ossification or osteoporosis, but its diagnostic value needs validation. There is still a lack of stable and efficient methods of measuring serum DKK-1 levels suitable for longitude studies.

Role of R-Loop Structure in Efficacy of RNA Elongation Synthesis by RNA Polymerase from .

The mechanism of transcription proceeds through the formation of R-loop structures containing a DNA-RNA heteroduplex and a single-stranded DNA segment that should be placed inside the elongation complex; therefore, these nucleic acid segments are limited in length. The attachment of each nucleotide to the 3' end of an RNA strand requires a repeating cycle of incoming nucleoside triphosphate binding, catalysis, and enzyme translocation. Within these steps of transcription elongation, RNA polymerase sequentially goes through several states and is post-translocated, catalytic, and pre-translocated.

Novel Core Gene Signature Associated with Inflammation-to-Metaplasia Transition in Influenza A Virus-Infected Lungs.

Respiratory infections caused by RNA viruses are a major contributor to respiratory disease due to their ability to cause annual epidemics with profound public health implications. Influenza A virus (IAV) infection can affect a variety of host signaling pathways that initiate tissue regeneration with hyperplastic and/or dysplastic changes in the lungs. Although these changes are involved in lung recovery after IAV infection, in some cases, they can lead to serious respiratory failure.

and Are Appropriate Reference Genes for Splenic Neutrophils Isolated from Healthy or Tumor-Bearing Mice.

/: Neutrophils have recently gained significant attention due to their heterogeneity in tumor settings. The gene expression profiles of neutrophils from different tumor types are of great interest. Murine splenic neutrophils reflect the immune status of the organism and could be a source of tumor-associated neutrophils in tumor-bearing mice.

Properties of phosphoramide benzoazole oligonucleotides (PABAOs). II. Structure and hybridization efficiency of N-benzoxazole derivatives.

New phosphate-modified nucleic acid derivatives are of great significance in basic research and biomedical applications. We have recently developed a new class of phosphoramide benzoazole oligonucleotides (PABAOs). In this work, th properties of N-benzoxazole oligodeoxyribonucleotides have been thoroughly examined.

Synthetic Lesions with a Fluorescein Carbamoyl Group As Analogs of Bulky Lesions Removable by Nucleotide Excision Repair: A Comparative Study on Properties.

Mammalian nucleotide excision repair (NER), known for its broad substrate specificity, is responsible for removal of bulky lesions from DNA. Over 30 proteins are involved in NER, which includes two distinct pathways: global genome NER and transcription-coupled repair. The complexity of these processes, the use of extended DNA substrates, and the presence of bulky DNA lesions induced by chemotherapy have driven researchers to seek more effective methods by which to assess NER activity, as well as to develop model DNAs that serve as efficient substrates for studying lesion removal.

Complex Inhibitory Activity of Pentacyclic Triterpenoids against Cutaneous Melanoma In Vitro and In Vivo: A Literature Review and Reconstruction of Their Melanoma-Related Protein Interactome.

Pentacyclic triterpenoids (PTs) are a class of plant metabolites with a wide range of pharmacological activities, including strong antitumor potential against skin malignancies. By acting on multiple signaling pathways that control key cellular processes, PTs are able to exert complex effects on melanoma progression in vitro and in vivo. In this review, we have analyzed the works published in the past decade and devoted to the effects of PTs, both natural and semisynthetic, on cutaneous melanoma pathogenesis, including not only their direct action on melanoma cells but also their influence on the tumor microenvironment and abberant melanogenesis, often associated with melanoma aggressiveness.

Study of Hard Protein Corona on Lipid Surface of Composite Nanoconstruction.

The composition of the protein corona covering any nanoparticle (NP) when it enters a biological fluid determines the parameters of the NP's interaction with the body. To "control" these parameters, it is important to know the composition of the protein corona, the determination of which is a complex task associated with the two-layer organization of the corona (hard and soft coronas). In a previous publication, we reported obtaining lipid-coated NPs with a full protein corona, isolating them, and proving the presence of the corona on the surface of the NPs.