Citologiâ

Breast cancer ranks first in terms of cancer incidence and mortality among the female population. The main cause of death from breast cancer, as with other malignant neoplasms, is tumor dissemination and the development of resistance to treatment. Chemokines have been found to play an important role in the progression of malignant neoplasms. In this short review, we describe the current understanding of the role of the most studied chemokine, CXCL12 and its receptors, CXCR4 and CXCR7 in the progression of breast cancer.

Mutations in the human KCNV2 gene cause a rare hereditary disease — cone dystrophy with supernormal rod response (CDSRR), characterized by progressive vision loss and impaired color discrimination. The KCNV2 gene encodes the Kv8.2 subunit of a potassium channel that is critical for the normal function of retinal photoreceptors. Gene therapy offers a promising treatment approach for this condition. To test the efficacy of gene therapy, an appropriate experimental disease model, such as a knockout mouse model, is required. This study focused on selecting optimal guide RNAs for knocking out the Kcnv2 gene using the CRISPR/Cas9 system and testing their efficiency in a mouse cell line. The selected guide RNAs can be utilized to generate a Kcnv2-/- mouse model.

A number of point mutations has been identified in the genes of contractile and regulatory proteins of skeletal muscle that can lead to dysfunction of muscle tissue. The molecular mechanisms of muscle contraction in the presence of mutant muscle proteins in the sarcomere remain poorly understood. In the current study, we examined the impact of the glutamate-to-alanine substitution at position 150 (Glu150Ala) of γ-tropomyosin associated with cap disease and fiber-type disproportion in humans on the molecular mechanisms of troponin-tropomyosin-related regulation of muscle contraction in a single muscle fiber. It is believed that tropomyosin residue Glu150 is not directly involved in the interaction of tropomyosin with actin and myosin interactions; however, according to structural models of thin filaments under low Ca²⁺ conditions, this residue is located close to site of binding with the C-terminal domain of troponin I. To assess the performance of myosin heads in the presence of Glu150Ala mutant tropomyosin, we measured the polarized fluorescence of 1,5-IAEDANS probe bound to the SH1-helix of myosin. The obtained results indicate an abnormal increase in the number of myosin heads strongly bound to actin during relaxation of muscle fibres containing Glu150Ala mutant tropomyosin. It has been shown that the green tea catechin epigallocatechin gallate (EGCG), known as a modulator of troponin function, inhibits the premature transition of myosin heads into a state of strong actin binding, and thus weakens the damaging effect of the mutation. However, EGCG does not completely restore the effective behavior of myosin cross-bridges during the ATPase cycle.

Hypochlorous acid and hypochlorite ions are formed in the halogenating cycle of myeloperoxidase, localized mainly in neutrophils, and play a primary role in antimicrobial protection. The paper presents the results of a study of the effect of exogenous HOCl/OCl^– in micromolar concentrations on the mechanisms of the “respiratory burst” formation by neutrophils stimulated to phagocytosis. It is shown that this oxidizer is capable of stimulating the functional activity of neutrophils, which is expressed in an increase in the yield of reactive oxygen and chlorine species (ROСS) and secretory degranulation of cells. Enhancement of the “respiratory burst” is associated with activation of NADPH oxidase, PI-3K, MAP kinase ERK1/2 and a decrease in the contribution of intracellular myeloperoxidase to ROСS production by neutrophils. It was found that HOCl/OCl^– in the studied concentrations is capable of inhibiting myeloperoxidase activity. It is suggested that hypochlorous acid should be considered as a new potential secondary messenger regulating neutrophil functions.

A study was conducted of the dynamics of changes in the population of GABAergic neurons and the protein content of the α1 subunit, which is included in of the GABA_A receptor (GABA_Aα1) in the CA1 and CA3 fields of the hippocampus during the neonatal period under normal conditions and after exposure to perinatal hypoxia. The study used a model of human premature pregnancy. Exposure to hypoxia was carried out on the 2nd day after birth, in a special chamber with oxygen content in the respiratory mixture of 7.8%. Immunohistochemical research methods were used to detect GABA and the α1 GABA_A receptor subunit protein. The hippocampus was studied on days 5 and 10. It was shown that in control animals during the neonatal period, in fields CA1 and CA3, there is a gradual increase in the population of GABAergic neurons, an increase in the content of GABA itself and the protein of the α1 GABA_A receptor subunit. Asphyxia during the perinatal period leads to a reduction in the number of GABAergic neurons in both fields CA1 and CA3, a decrease in the content of GABA itself, the protein of the α1 subunit of the GABA_A receptor and a delay in the development of the neuropil. Thus, in animals that have experienced asphyxia, by the end of the neonatal period, changes in the organization of the GABAergic system are already expressed in parts of the hippocampus, which can lead to dysfunction of the inhibitory system already at the earliest stages of development.