Moonlight functions of glycolytic enzymes in cancer.

Since an extensive genome research has started, basic principle "one gene-one protein-one function" was significantly revised. Many proteins with more than one function were identified and characterized as "moonlighting" proteins, which activity depend not only on structural peculiarities but also on compartmentation and metabolic environment. It turned out that "housekeeping" glycolytic enzymes show important moonlight functions such as control of development, proliferation, apoptosis, migration, regulation of transcription and cell signaling. Glycolytic enzymes emerged very early in evolution and because of the limited content of genomes, they could be used as ancient regulators for intercellular and intracellular communication. The multifunctionality of the constitutively expressed enzymes began to serve cancer cell survival and growth. In the present review we discuss some moonlight functions of glycolytic enzymes that important for malignant transformation and tumor growth.

Cytogenetic Damage Induced by Radioiodine Therapy: A Follow-Up Case Study.

The risk of toxicity attributable to radioiodine therapy (RIT) remains a subject of ongoing research, with a whole-body dose of 2 Gy proposed as a safe limit. This article evaluates the RIT-induced cytogenetic damage in two rare differentiated thyroid cancer (DTC) cases, including the first follow-up study of a pediatric DTC patient. Chromosome damage in the patient's peripheral blood lymphocytes (PBL) was examined using conventional metaphase assay, painting of chromosomes 2, 4, and 12 (FISH), and multiplex fluorescence in situ hybridization (mFISH). Patient 1 (female, 1.6 y.o.) received four RIT courses over 1.1 years. Patient 2 (female, 49 y.o.) received 12 courses over 6.4 years, the last two of which were examined. Blood samples were collected before and 3-4 days after the treatment. Chromosome aberrations (CA) analyzed by conventional and FISH methods were converted to a whole-body dose accounting for the dose rate effect. The mFISH method showed an increase in total aberrant cell frequency following each RIT course, while cells carrying unstable aberrations predominated in the yield. The proportion of cells containing stable CA associated with long-term cytogenetic risk remained mostly unchanged during follow-up for both patients. A one-time administration of RIT was safe, as the threshold of 2 Gy for the whole-body dose was not exceeded. The risk of side effects projected from RIT-attributable cytogenetic damage was low, suggesting a good long-term prognosis. In rare cases, such as the ones reviewed in this study, individual planning based on cytogenetic biodosimetry is strongly recommended.

Assessment of Proliferation and Apoptosis in Testes of Rats after Experimental Localized Electron Irradiation.

BACKGROUND AND PURPOSE: With the emergence of linear accelerators in radiotherapy, it becomes necessary to accurately select new dosing regimens. The purpose of this study was to assess the morphological changes of spermatogenesis after radiation exposure. MATERIALS AND METHODS: Male Wistar rats (n = 40) were subjected to targeted ionizing radiation on a pulsed electron accelerator "NOVAC-11" with doses of 2, 8 and 12 Gy. Spermatogenesis was assessed a week later using light microscopy and immunohistochemical method (antibodies to Ki-67, Bcl-2, p53, Caspase 3). RESULTS: A decrease in the number of normal germ cells was seen in all experimental groups, while radioresistant Sertoli and Leydig cells were barely affected. The most serious damage to the tubules and germ cells was observed in 8 and 12 Gy irradiation groups. IHC analysis of testes after irradiation showed a shift in the proliferative-apoptotic balance toward apoptosis of germ cells: a decrease in the expression levels of Ki-67 and Bcl-2, an increase in p53-positive and caspase 3-positive cells by the end of the experiment. CONCLUSION: Dose-dependent progressive pathomorphological changes in histoarchitectonics of the testes are traced, and a decrease in the number of germ cells is seen on the seventh day after irradiation with a pulsed electron accelerator "NOVAC-11".

Evolutionary View on Lactate-Dependent Mechanisms of Maintaining Cancer Cell Stemness and Reprimitivization.

The role of lactic acid (lactate) in cell metabolism has been significantly revised in recent decades. Initially, lactic acid was attributed to the role of a toxic end-product of metabolism, with its accumulation in the cell and extracellular space leading to acidosis, muscle pain, and other adverse effects. However, it has now become obvious that lactate is not only a universal fuel molecule and the main substrate for gluconeogenesis but also one of the most ancient metabolites, with a signaling function that has a wide range of regulatory activity. The Warburg effect, described 100 years ago (the intensification of glycolysis associated with high lactate production), which is characteristic of many malignant tumors, confirms the key role of lactate not only in physiological conditions but also in pathologies. The study of lactate's role in the malignant transformation becomes more relevant in the light of the "atavistic theory of carcinogenesis," which suggests that tumor cells return to a more primitive hereditary phenotype during microevolution. In this review, we attempt to summarize the accumulated knowledge about the functions of lactate in cell metabolism and its role in the process of carcinogenesis and to consider the possible evolutionary significance of the Warburg effect.

Angiotensin-Converting Enzyme 2 and Furin Expression in the Appendix of Children with COVID-19.

Background: The sudden outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in more than 261 million infections and an estimated 5.1 million deaths. Some vital organs such as the kidneys, heart, intestines, and lungs could be damaged by SARS-CoV-2. Questions remain regarding the effect of SARS-CoV-2 on the mucous membrane of the appendix in children. The aim of this study was to evaluate the knowledge of cytologic processes in appendix tissue in children with coronavirus disease 2019 (COVID-19). Patients and Methods: Fragments of the appendices of children with confirmed COVID-19 (n = 42) were studied by real-time polymerase chain reaction (PCR) to determine the expression of SARS-CoV-2 RNA and genes encoding protein complexes: ACE-2 and Furin. Results: We found traces of coronavirus genetic material in the appendices of children with COVID-19. We also found increased expression of ACE-2 and Furin in the tissue, which indicates favorable conditions for coronavirus infection. Conclusions: Viral load in the appendices of children can be reported based on the results of real-time PCR for SARS-CoV-2 and the expression of ACE-2 and Furin.