The association of rs25487 of the XRCC1 gene and rs13181 of the ERCC2 gene polymorphisms with the ovarian cancer risk.

Ovarian cancer (OC) is the most lethal gynecological cancer worldwide. DNA damage plays an important role in cancer development, and the proteins encoded by XRCC1 and ERCC2 are important components of the DNA repair system. This study aimed to examine the relationship between the rs25487 XRCC1 and rs13181 ERCC2 polymorphisms and the risk of OC development in women from the Moscow region.

Biologics-based technologies for highly efficient and targeted RNA delivery.

The demand for RNA-based therapeutics is increasing globally. However, their use is hampered by the lack of safe and effective delivery vehicles. Here, we developed technologies for highly efficient delivery of RNA cargo into programmable extracellular vesicle-mimetic nanovesicles (EMNVs) by fabricating hybrid EMNV-liposomes (Hybs).

Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy Individuals.

Background/objectives: The development of blood tests for the early detection of individual predisposition to socially significant diseases remains a pressing issue.

Methods: In this pilot study, multiple reaction monitoring mass spectrometry (MRM-MS) with a BAK-270 assay was applied for protein concentrations analysis in blood plasma from 21 healthy volunteers of the European cohort.

Results: The levels of 138 plasma proteins were reliably and precisely quantified in no less than 50% of samples.

Saponin is Essential for the Isolation of Proteins and RNA from Biological Nanoparticles.

Extracellular vesicles (EVs), biomimetics, and other biological nanoparticles (BNs) produced from human cells are gaining increasing attention in the fields of molecular diagnostics and nanomedicine for the delivery of therapeutic cargo. In particular, BNs are considered prospective delivery vehicles for different biologics, including protein and RNA therapeutics. Moreover, EVs are widely used in molecular diagnostics for early detection of disease-associated proteins and RNA.

Regulatory Role and Cytoprotective Effects of Exogenous Recombinant SELENOM under Ischemia-like Conditions and Glutamate Excitotoxicity in Cortical Cells In Vitro.

Despite the successes in the prevention and treatment of strokes, it is still necessary to search for effective cytoprotectors that can suppress the damaging factors of cerebral ischemia. Among the known neuroprotectors, there are a number of drugs with a protein nature. In the present study, we were able to obtain recombinant SELENOM, a resident of the endoplasmic reticulum that exhibits antioxidant properties in its structure and functions.

Zinc for GNAO1 encephalopathy: Preclinical profiling and a clinical case.

Background: De novo pathogenic variants in GNAO1-the gene encoding the major neuronal G protein Gαo-cause pediatric encephalopathies and other neurological deficiencies largely refractory to available therapies. Zn emerged to restore guanosine triphosphate hydrolysis and cellular interactions of pathogenic Gαo; dietary zinc salt supplementation improves lifespan and motoric function in a Drosophila disease model.

Methods: Using biochemical, animal, and first-in-human studies, we provide support for the patient stratification and application of zinc acetate in GNAO1-associated disorders.

Polymicrobial consortia in the pathogenesis of biofilm vaginosis visualized by FISH. Historic review outlining the basic principles of the polymicrobial infection theory.

The manuscript disputes the exclusive mono-infectious way of thinking, which presumes that for every infection only one pathogen is responsible and sufficient, when infectious vectors, close contact and reduced immunity meet. In situations involving heavily colonized anatomical sites such an approach often ends in insoluble contradictions. Upon critical reflection and evaluation of 20 years research on spatial organization of vaginal microbiota it is apparent, that in some situations, pathogens may act and operate in permanent, structurally organized consortia, whereas its individual components may be innocuous and innocent, failing to express any pathogenic effect.

Effects of Lithium Ions on tPA-Induced Hemorrhagic Transformation under Stroke.

Thrombolytic therapy with the tissue plasminogen activator (tPA) is a therapeutic option for acute ischemic stroke. However, this approach is subject to several limitations, particularly the increased risk of hemorrhagic transformation (HT). Lithium salts show neuroprotective effects in stroke, but their effects on HT mechanisms are still unknown.

Swelling, Rupture and Endosomal Escape of Biological Nanoparticles Per Se and Those Fused with Liposomes in Acidic Environment.

Biological nanoparticles (NPs), such as extracellular vesicles (EVs), exosome-mimetic nanovesicles (EMNVs) and nanoghosts (NGs), are perspective non-viral delivery vehicles for all types of therapeutic cargo. Biological NPs are renowned for their exceptional biocompatibility and safety, alongside their ease of functionalization, but a significant challenge arises when attempting to load therapeutic payloads, such as nucleic acids (NAs). One effective strategy involves fusing biological NPs with liposomes loaded with NAs, resulting in hybrid carriers that offer the benefits of both biological NPs and the capacity for high cargo loads.

Changes in the Transcription of Proliferation- and Apoptosis-Related Genes in Embryos in Women of Different Ages under the Influence of Extracellular Vesicles from Donor Follicular Fluid In Vitro.

We studied the influence of extracellular vesicles from the follicular fluid of a young donor on gene expression (MKI67, MYBL2, CCNB1, CCND1, CCNE1, CALM2, BAX, NDRG1, TP53I3, VEGF, VCAN, HAS2, CTSL2, PIBF1, RPL37, PFKP, GPX3, and AQP3) in embryos of women of different ages. According to nanoparticle tracking analysis data, the concentration of extracellular vesicles was 3.75±0.

Targeting Mitochondria for Cancer Treatment.

There is an increasing accumulation of data on the exceptional importance of mitochondria in the occurrence and treatment of cancer, and in all lines of evidence for such participation, there are both energetic and non-bioenergetic functional features of mitochondria. This analytical review examines three specific features of adaptive mitochondrial changes in several malignant tumors. The first feature is characteristic of solid tumors, whose cells are forced to rebuild their energetics due to the absence of oxygen, namely, to activate the fumarate reductase pathway instead of the traditional succinate oxidase pathway that exists in aerobic conditions.

Mitocentricity.

Worldwide, interest in mitochondria is constantly growing, as evidenced by scientific statistics, and studies of the functioning of these organelles are becoming more prevalent than studies of other cellular structures. In this analytical review, mitochondria are conditionally placed in a certain cellular center, which is responsible for both energy production and other non-energetic functions, without which the existence of not only the eukaryotic cell itself, but also the entire organism is impossible. Taking into account the high multifunctionality of mitochondria, such a fundamentally new scheme of cell functioning organization, including mitochondrial management of processes that determine cell survival and death, may be justified.

Diagnostic Role of Cell-Free miRNAs in Identifying Placenta Accreta Spectrum during First-Trimester Screening.

Placenta accreta spectrum (PAS) is a severe complication of pregnancy associated with excessive invasion of cytotrophoblast cells at the sites of the endometrial-myometrial interface and the myometrium itself in cases of adherent (creta) and invasive (increta and percreta) forms, respectively. This leads to a high risk of massive blood loss, maternal hysterectomy, and preterm birth. Despite advancements in ultrasound protocols and found associations of alpha-fetoprotein, PAPP-A, hCG, PLGF, sFlt-1, IL-8, and IL-33 peripheral blood levels with PAS, there is a high need for an additional non-invasive test to improve the diagnostic accuracy and to select the real PAS from the suspected ones in the first-trimester screening.

A Novel Anti-CD47 Nanobody Tetramer for Cancer Therapy.

CD47 acts as a defense mechanism for tumor cells by sending a "don't eat me" signal via its bond with SIRPα. With CD47's overexpression linked to poor cancer outcomes, its pathway has become a target in cancer immunotherapy. Though monoclonal antibodies offer specificity, they have limitations like the large size and production costs.

Lactate protects neurons and astrocytes against ischemic injury by modulating Ca homeostasis and inflammatory response.

Lactate is now considered an additional fuel or signaling molecule in the brain. In this study, using an oxygen-glucose deprivation (OGD) model, we found that treatment with lactate inhibited the global increase in intracellular calcium ion concentration ([Ca]) in neurons and astrocytes, decreased the percentage of dying cells, and caused a metabolic shift in astrocytes and neurons toward aerobic oxidation of substrates. OGD resulted in proinflammatory changes and increased expression of cytokines and chemokines, whereas incubation with lactate reduced these changes.

Different Patterns of Vascularization in Preinvasive States and at the Initial Stages of Invasive Growth of the Neoplasms.

Tissue samples obtained during surgery from 90 patients with malignant neoplasms of various localizations were studied (the presence of precancerous dysplastic alterations and their transition to invasive cancer in the slides were obligatory condition). In addition to traditional histological methods, immunohistochemical reactions for detection of HIF-1α, GLUT1, CAIX, and CD31 were performed. At the precancerous stage including cancer in situ, progressive signs of reduced blood vessel density and hypoxia were observed.

The effects of antibiotic therapy on neonatal sepsis-associated acute kidney injury.

Aim: Neonatal sepsis remains one of the most dangerous conditions in the neonatal intensive care units. One of the organs affected by sepsis is the kidney, making acute kidney injury (AKI) a common complication of sepsis. Treatment of sepsis almost always involves antibiotic therapy, which by itself may cause some adverse effects, including nephrotoxicity.

Biomarkers of the End-Stage Renal Disease Progression: Beyond the GFR.

Chronic kidney disease can progress to the end-stage renal disease (ESRD) characterized by a high risk of morbidity and mortality. ESRD requires immediate therapy or even dialysis or kidney transplantation, therefore, its timely diagnostics is critical for many patients. ESRD is associated with pathological changes, such as inflammation, fibrosis, endocrine disorders, and epigenetic changes in various cells, which could serve as ESRD markers.

Mitochondrial Network: Electric Cable and More.

Mitochondria in a cell can unite and organize complex, extended structures that occupy the entire cellular volume, providing an equal supply with energy in the form of ATP synthesized in mitochondria. In accordance with the chemiosmotic concept, the oxidation energy of respiratory substrates is largely stored in the form of an electrical potential difference on the inner membrane of mitochondria. The theory of the functioning of extended mitochondrial structures as intracellular electrical wires suggests that mitochondria provide the fastest delivery of electrical energy through the cellular volume, followed by the use of this energy for the synthesis of ATP, thereby accelerating the process of ATP delivery compared to the rather slow diffusion of ATP in the cell.

Circulating Tumor DNA Is a Variant of Liquid Biopsy with Predictive and Prognostic Clinical Value in Breast Cancer Patients.

This paper introduces the reader to the field of liquid biopsies and cell-free nucleic acids, focusing on circulating tumor DNA (ctDNA) in breast cancer (BC). BC is the most common type of cancer in women, and progress with regard to treatment has been made in recent years. Despite this, there remain a number of unresolved issues in the treatment of BC; in particular, early detection and diagnosis, reliable markers of response to treatment and for the prediction of recurrence and metastasis, especially for unfavorable subtypes, are needed.

Extracellular vesicles of human glial cells exert neuroprotective effects via brain miRNA modulation in a rat model of traumatic brain injury.

Stem cell-based therapeutic approaches for neurological disorders are widely studied. Paracrine factors secreted by stem cells in vitro and delivered intranasally might allow bypassing the disadvantages associated with a surgical cell delivery procedure with likely immune rejection of a transplant. In this study, we investigated the therapeutic effect of the extracellular vesicles secreted by glial progenitor cells (GPC-EV) derived from human induced pluripotent stem cell in a traumatic brain injury model.

Novel Approaches to Possible Targeted Therapies and Prophylaxis of Uterine Fibroids.

Uterine leiomyomas are the most common benign tumors in women of childbearing age. They may lead to problems of conception or complications during the gestational period. The methods of treatment include surgical (myomectomy and hysterectomy, embolization of arteries) and therapeutic treatment (ulipristal acetate, leuprolide acetate, cetrorelix, goserelin, mifepristone).