DNA Methylation in Cancer Epigenetics

DNA methylation is one of the most important epigenetic modifications next to acetylation or histone modifications, as it has a role in the homeostatic control of the cell and is strongly involved in the control of genome expression. DNA methylation, which is catalyzed by DNA methyltransferases (DNMTs), is one of the primary epigenetic mechanisms that control cell proliferation, apoptosis, differentiation, cell cycle, and transformation in eukaryotes. Hypomethylation and hypermethylation result in the activation or repression of genes and in a normal cell there is a strict balance between these processes. Abnormal DNA methylation is a well-known feature of cancer development and progression and can turn normal stem cells into cancer stem cells. Studies clearly show that DNA methylation regulates gene transcription functions in cancer pathogenesis. In cancer cells, DNA methylation patterns are largely modified, and therefore, methylation is used to distinguish cancer cells from normal, healthy cells. However, the mechanisms underlying changes in DNA methylation remain unexplored. However, it is known that oxidative stress (OS) is a key mechanism of carcinogenesis, and DNA methylation of genes that are active at OS may play a role in cancer development. Studies also show that DNA methylation is mediated by long noncoding RNA (lncRNA) under both physiological and pathological conditions. How cell-specific DNA methylation patterns are established or disrupted is a key question in developmental biology and cancer epigenetics

Regulation of Seed Dormancy and Germination Mechanisms in a Changing Environment

Environmental conditions are the basis of plant reproduction and are the critical factors controlling seed dormancy and germination. Global climate change is currently affecting environmental conditions and changing the reproduction of plants from seeds. Disturbances in germination will cause disturbances in the diversity of plant communities. Models developed for climate change scenarios show that some species will face a significant decrease in suitable habitat area. Dormancy is an adaptive mechanism that affects the probability of survival of a species. The ability of seeds of many plant species to survive until dormancy recedes and meet the requirements for germination is an adaptive strategy that can act as a buffer against the negative effects of environmental heterogeneity. The influence of temperature and humidity on seed dormancy status underlines the need to understand how changing environmental conditions will affect seed germination patterns. Knowledge of these processes is important for understanding plant evolution and adaptation to changes in the habitat. The network of genes controlling seed dormancy under the influence of environmental conditions is not fully characterized. Integrating research techniques from different disciplines of biology could aid understanding of the mechanisms of the processes controlling seed germination. Transcriptomics, proteomics, epigenetics, and other fields provide researchers with new opportunities to understand the many processes of plant life. This paper focuses on presenting the adaptation mechanism of seed dormancy and germination to the various environments, with emphasis on their prospective roles in adaptation to the changing climate

Can Forest Trees Cope with Climate Change?—Effects of DNA Methylation on Gene Expression and Adaptation to Environmental Change

Epigenetic modifications, including chromatin modifications and DNA methylation, play key roles in regulating gene expression in both plants and animals. Transmission of epigenetic markers is important for some genes to maintain specific expression patterns and preserve the status quo of the cell. This article provides a review of existing research and the current state of knowledge about DNA methylation in trees in the context of global climate change, along with references to the potential of epigenome editing tools and the possibility of their use for forest tree research. Epigenetic modifications, including DNA methylation, are involved in evolutionary processes, developmental processes, and environmental interactions. Thus, the implications of epigenetics are important for adaptation and phenotypic plasticity because they provide the potential for tree conservation in forest ecosystems exposed to adverse conditions resulting from global warming and regional climate fluctuations

Regulation of Seed Dormancy and Germination Mechanisms in a Changing Environment

Environmental conditions are the basis of plant reproduction and are the critical factors controlling seed dormancy and germination. Global climate change is currently affecting environmental conditions and changing the reproduction of plants from seeds. Disturbances in germination will cause disturbances in the diversity of plant communities. Models developed for climate change scenarios show that some species will face a significant decrease in suitable habitat area. Dormancy is an adaptive mechanism that affects the probability of survival of a species. The ability of seeds of many plant species to survive until dormancy recedes and meet the requirements for germination is an adaptive strategy that can act as a buffer against the negative effects of environmental heterogeneity. The influence of temperature and humidity on seed dormancy status underlines the need to understand how changing environmental conditions will affect seed germination patterns. Knowledge of these processes is important for understanding plant evolution and adaptation to changes in the habitat. The network of genes controlling seed dormancy under the influence of environmental conditions is not fully characterized. Integrating research techniques from different disciplines of biology could aid understanding of the mechanisms of the processes controlling seed germination. Transcriptomics, proteomics, epigenetics, and other fields provide researchers with new opportunities to understand the many processes of plant life. This paper focuses on presenting the adaptation mechanism of seed dormancy and germination to the various environments, with emphasis on their prospective roles in adaptation to the changing climate

Diagnosis of <i>Hymenoptera</i> Venom Allergy: State of the Art, Challenges, and Perspectives

Hymenoptera venom allergy is the most common cause of anaphylaxis in adults and the second-most frequent in children. The proper diagnosis of this life-threatening allergy remains a challenge. This review focuses on the current knowledge regarding diagnostics of Hymenoptera venom allergy. The paper includes a brief description of the representatives of Hymenoptera order and the composition of their venoms. Then, diagnostic tests for allergy to Hymenoptera venom are described. Common diagnostic problems, especially double positivity in tests for IgE antibodies specific to honeybee and wasp venom, are also discussed. Special attention is paid to the search for new diagnostic capabilities using modern methodologies. Multidimensional molecular analysis offers an opportunity to characterize changes in body fluids associated with Hymenoptera venom allergy and yields a unique insight into the cell status. Despite recent developments in the diagnostics of Hymenoptera venom allergy, new testing methodologies are still needed to answer questions and doubts we have

Tricyclic Derivative of Acyclovir and Its Esters in Relation to the Esters of Acyclovir Enzymatic Stability: Enzymatic Stability Study

The 3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-6-(4-methoxyphenyl)-9-oxo-5H-imidazo[1,2-a]&ndash;purine (6-(4-MeOPh)-TACV) was selected to assess the enzymatic stability of the tricyclic acyclovir derivatives from the imidazo[1,2-a]-purine group. The parent compound and its esters (acetyl, isobutyryl, pivaloyl, nicotinic, ethoxycarbonyl) were subjected to kinetic studies and compared with the stability of analogous acyclovir (ACV) esters. The enzymatic hydrolysis was observed in vitro in a medium of 80% human plasma in the absence and presence of porcine liver esterase (PLE). The tests were carried out at 37 &deg;C. To determine the kinetic parameters (kobs., t0.5) of the observed reaction, the validated HPLC-UV method in the reversed phase was used. The HPLC-MS/MS method was used to identify the degradation products under the tested conditions. In summary, it was found that 6-(4-MeOPh)-TACV esters are more susceptible to esterase metabolism than ACV esters. It was confirmed by HPLC-MS/MS that in the plasma, the main product of their hydrolysis is 6-(4-MeOPh)-TACV and not ACV, which confirms that their antiviral activity observed in vitro does not result from ring degradation

Mitochondrial Peroxiredoxin-IIF (PRXIIF) Activity and Function during Seed Aging

Klupczyńska EA, Dietz K-J, Małecka A, Ratajczak E. Mitochondrial Peroxiredoxin-IIF (PRXIIF) Activity and Function during Seed Aging. Antioxidants. 2022;11(7): 1226.Mitochondria play a major role in energy metabolism, particularly in cell respiration, cellular metabolism, and signal transduction, and are also involved in other processes, such as cell signaling, cell cycle control, cell growth, differentiation and apoptosis. Programmed cell death is associated with the production of reactive oxygen species (ROS) and a concomitant decrease in antioxidant capacity, which, in turn, determines the aging of living organisms and organs and thus also seeds. During the aging process, cell redox homeostasis is disrupted, and these changes decrease the viability of stored seeds. Mitochondrial peroxiredoxin-IIF (PRXIIF), a thiol peroxidase, has a significant role in protecting the cell and sensing oxidative stress that occurs during the disturbance of redox homeostasis. Thioredoxins (TRXs), which function as redox transmitters and switch protein function in mitochondria, can regulate respiratory metabolism. TRXs serve as electron donors to PRXIIF, as shown in Arabidopsis. In contrast, sulfiredoxin (SRX) can regenerate mitochondrial PRXIIF once hyperoxidized to sulfinic acid. To protect against oxidative stress, another type of thiol peroxidases, glutathione peroxidase-like protein (GPXL), is important and receives electrons from the TRX system. They remove peroxides produced in the mitochondrial matrix. However, the TRX/PRX and TRX/GPXL systems are not well understood in mitochondria. Knowledge of both systems is important because these systems play an important role in stress sensing, response and acclimation, including redox imbalance and generation of ROS and reactive nitrogen species (RNS). The TRX/PRX and TRX/GPXL systems are important for maintaining cellular ROS homeostasis and maintaining redox homeostasis under stress conditions. This minireview focuses on the functions of PRXIIF discovered in plant cells approximately 20 years ago and addresses the question of how PRXIIF affects seed viability maintenance and aging. Increasing evidence suggests that the mitochondrial PRXIIF plays a major role in metabolic processes in seeds, which was not previously known

Amino Acids in Cerebrospinal Fluid of Patients with Aneurysmal Subarachnoid Haemorrhage: An Observational Study

BackgroundThe authors are aware of only one article investigating amino acid concentrations in cerebrospinal fluid (CSF) in patients with ruptured intracranial aneurysms, and this was published 31 years ago. Since then, both management of subarachnoid haemorrhage (SAH) and amino acid assay techniques have seen radical alterations, yet the pathophysiology of SAH remains unclear.ObjectiveTo analyse the pattern of concentrations of amino acids and related compounds in patients with different outcomes following aneurysmal SAH.Methods49 CSF samples were collected from 23 patients on days 0–3, 5, and 10 post-SAH. Concentrations of 33 amino acids and related compounds were assayed by liquid chromatography tandem mass spectrometry in patients with good [Glasgow Outcome Scale (GOS) 1–3] and poor (GOS 4–5) outcome.ResultsOf the 33 compounds assayed, only hydroxyproline and 3-aminoisobutyric acid appeared not to increase significantly following SAH. In poor outcome patients, we found significantly higher concentrations of aspartic acid (p = 0.038), glutamic acid (p = 0.038), and seven other compounds on days 0–3 post-SAH; glutamic acid (p = 0.041) on day 5 post-SAH, and 2-aminoadipic acid (p = 0.033) on day 10 post-SAH. The most significant correlation with GOS at 3 months was found for aminoadipic acid on day 10 post-SAH (cc = −0.81).ConclusionAneurysmal rupture leads to a generalised increase of amino acids and related compounds in CSF. The patterns differ between good and poor outcome cases. Increased excitatory amino acids are strongly indicative of poor outcome

Effects of a Honeybee Sting on the Serum Free Amino Acid Profile in Humans

<div><p>The aim of this study was to assess the response to a honeybee venom by analyzing serum levels of 34 free amino acids. Another goal of this study was to apply complex analytic-bioinformatic-clinical strategy based on up-to-date achievements of mass spectrometry in metabolomic profiling. The amino acid profiles were determined using hybrid triple quadrupole/linear ion trap mass spectrometer coupled with a liquid chromatography instrument. Serum samples were collected from 27 beekeepers within 3 hours after they were stung and after a minimum of 6 weeks following the last sting. The differences in amino acid profiles were evaluated using MetaboAnalyst and ROCCET web portals. Chemometric tests showed statistically significant differences in the levels of L-glutamine (Gln), L-glutamic acid (Glu), L-methionine (Met) and 3-methyl-L-histidine (3MHis) between the two analyzed groups of serum samples. Gln and Glu appeared to be the most important metabolites for distinguishing the beekeepers tested shortly after a bee sting from those tested at least 6 weeks later. The role of some amino acids in the response of an organism to the honeybee sting was also discussed. This study indicated that proposed methodology may allow to identify the individuals just after the sting and those who were stung at least 6 weeks earlier. The results we obtained will contribute to better understanding of the human body response to the honeybee sting.</p></div