Nucleic Acid Damage Research Articles

Bacteria and RNA virus inactivation with a high-irradiance UV-A source

AbstractDisinfection with LED lamps is a promising ecological and economical substitute for mercury lamps. However, the optimal time/dose relationship needs to be established. Pathogen inactivation by UV-A primarily relies on induced reactive oxygen species (ROS) formation and subsequent oxidative damage. While effective against bacteria and enveloped viruses, non-enveloped viruses are less sensitive. In this study, we explored the disinfection properties of 10 W UV-A LED, emitting in the 365–375 nm range. UV-A at high values of irradiance (~ 0.46 W/cm2) can potentially induce ROS formation and direct photochemical damage of the pathogen nucleic acids, thus improving the disinfection. The UV-A inactivation was evaluated for the bacterium Escherichia coli (E. coli), non-enveloped RNA bacteriophage MS2, and enveloped mammalian RNA virus—Semliki Forest virus (SFV). The 4 log10 reduction doses for E. coli and SFV were 268 and 241 J/cm2, respectively. Furthermore, in irradiated E. coli, ROS production positively correlated with the inactivation rate. In the case of MS2 bacteriophage, the 2.5 log10 inactivation was achieved by 679 J/cm2 within 30 min of irradiation. The results demonstrate significant disinfection efficiency of non-enveloped virus MS2 using high-irradiance UV-A. This suggests a potential strategy for improving the inactivation of UV-A-unsusceptible pathogens, particularly non-enveloped viruses. Additionally, the direct UV-A irradiation of self-replicating viral RNA from SFV led to a significant loss of viral gene expression in cells transfected with the irradiated RNA. Therefore, the virus inactivation mechanism of high-irradiance UV-A LED can be partially determined by the direct damage of viral RNA. Graphical abstract

Bioaccumulation and Translocation of Heavy Metals in Solanum elaeagnifolium

Heavy metal pollution is becoming an increasingly common problem. Heavy metals including Chromium, Cadmium, Mercury, Copper, and lead are hazardous environmental pollutants, especially in high anthropogenic activity areas. Heavy metals accretion in soil is a serious concern for agricultural productivity due to its negative influence on food safety, market potential, and the phytotoxicity it causes in crops. Plant ascendancy and metabolic processes affect the geological and biological re-distribution of heavy metals through air, soil, and water pollution. The typical result of heavy metals toxicity is excessive accumulation of reactive methylglyoxal and oxygen species, which lead to lipid peroxidation, enzyme inactivation, nucleic acid damage, and protein oxidation in plants. In this study, bioaccumulation and Translocation of Heavy Metals in Solanum elaeagnifolium was conducted by using standard biological techniques. Twenty-four samples of both shoot and root systems collected ‎from the study sites and Three replications of soil samples from each habitat, including topsoil (0-50 cm depth) were studied.our results showed that the quantitative concentration of heavy metals in the shoots of S. elaeagnifolium for each metal indicated a high enrichment value for (Cr), (Fe), and (Mn), on the other hand, it showed low enrichment values for (Ni) & (Pb). In addition, the concentration of heavy metals in the roots of the plant was differentiated.

The Role of PGPB-Microalgae interaction in Alleviating Salt Stress in Plants.

Plant development and yield are severely hampered by climate change. Plants are very prone to a variety of abiotic stressors during growth, making them susceptible to destruction which can reduce the productivity by 20-60%. These stresses generate reactive oxygen species (ROS), which damage lipids, proteins, and nucleic acids. Microalgae and plant growth-promoting bacteria (PGPB) are remarkably effective at reducing the effects of salt stress and promoting plant growth, thereby increasing agricultural yield, and helping ensure global food security. Through a variety of mechanisms, including the production of phytohormones, 1-aminocyclopropane-1-carboxylic acid deaminase, exopolysaccharide, siderophores, hydrogen cyanide, extracellular polymeric substances, volatile organic compounds, and modulation of antioxidants defense machinery under abiotic stresses promote plant growth after inoculation of PGPB and microalgae. These microorganisms also maintain ion homeostasis, offer osmotic balance, stimulate genes that respond to salt and drought, rewire the metabolism, modify the transcription of ion transporter genes, and more. To counteract the negative consequences of salinity stress, this study summarizes the effects of PGPB- microalgae along with a tentative protective mechanism during salinity stress for sustainable agriculture.

The Effect of Oxidative Stress and Antioxidants Treatment on Gestational Diabetes Mellitus Outcome: A Scoping Review.

Diagnosing a pregnant woman's glucose intolerance is referred to as gestational diabetes mellitus (GDM). Diabetes has been linked to enhanced oxidative stress. In this condition, oxidative stress may damage nucleic acids, fats, and proteins, which in turn affects cell and tissue functions. The present study highlights the relationship between oxidative stress and GDM, with a particular focus on the role of hyperglycemia-induced processes during reactive oxygen species (ROS) oversupply, followed by it discusses the oxidative stress biomarkers and assesses the effects of antioxidant supplements on glycemic control, inflammatory processes, and oxidative stress among individuals with GDM. Two reviewers conducted a comprehensive literature search utilizing the PubMed®, Web of Science™, and Scopus® databases. Only items published in the English language up until June 2024 were taken into account. We conducted a thorough search of research databases to identify articles that had the terms "oxidative stress" or "antioxidant" and "GDM". From this search, we selected 55 relevant papers to be included in this narrative review. Pregnancy-induced hypertension, postpartum bleeding, lower birth weight, a higher risk of hyperbilirubinemia in their neonates, fetal growth retardation, and birth asphyxia were revealed to be outcomes of women enduring major oxidative stress during pregnancy. Furthermore, tight glycemic control both before and throughout pregnancy as well as oxidative stress treatment may help women highly prone to GDM.

Unveiling the crucial role of oxidative stress on steroid hormone receptors

ABSTRACT Oxidative stress is widely recognized as a major contributor to male infertility. Reactive oxygen species (ROS) can interact with various cellular components, causing irreversible damage to the male reproductive system. This damage results in several adverse effects, including impaired sperm motility, abnormal spermatogenesis, sperm deoxyribonucleic acid (DNA) damage, and altered steroidogenesis. Furthermore, oxidative damage to steroid hormone receptors contributes to their functional impairment. These factors, individually or collectively, lead to infertility or subfertility in men. ROS can damage proteins, lipids, and nucleic acids, with oxidative DNA damage potentially causing mutations, particularly in germ cells, as studies have shown. Such damage is also observed in steroid hormones and their receptors in men. Understanding the relationship between oxidative stress and its impact on genes is crucial for the accurate diagnosis, recognition, and treatment of male infertility. High-dose antioxidant supplementation, a beacon of hope, may eliminate, scavenge, or neutralize ROS, thereby mitigating ROS-induced genomic damage and oxidative harm to steroid hormones. Consequently, this approach may be considered the primary remedy against oxidative stress-induced male infertility.

The ribotoxic stress response drives UV-mediated cell death

While ultraviolet (UV) radiation damages DNA, eliciting the DNA damage response (DDR), it also damages RNA, triggering transcriptome-wide ribosomal collisions and eliciting a ribotoxic stress response (RSR). However, the relative contributions, timing, and regulation of these pathways in determining cell fate is unclear. Here we use time-resolved phosphoproteomic, chemical-genetic, single-cell imaging, and biochemical approaches to create a chronological atlas of signaling events activated in cells responding to UV damage. We discover that UV-induced apoptosis is mediated by the RSR kinase ZAK and not through the DDR. We identify two negative-feedback modules that regulate ZAK-mediated apoptosis: (1) GCN2 activation limits ribosomal collisions and attenuates ZAK-mediated RSR and (2) ZAK activity leads to phosphodegron autophosphorylation and its subsequent degradation. These events tune ZAK's activity to collision levels to establish regimes of homeostasis, tolerance, and death, revealing its key role as the cellular sentinel for nucleic acid damage.

Abstract 3760: The importance of optimizing DNA extraction conditions for formalin fixed paraffin embedded tissues

Abstract The pre-analytic extraction of Formalin Fixed Paraffin Embedded Tissues (FFPETs) appears to have a profound effect on the ability to obtain meaningful data from the DNA therein. FFPETs represent important materials in Pathology that are used to diagnose and analyze cancer. As part of preparing FFPETs, the formalin fixation step preserves the structure of tissues through covalent modifications but can also damage nucleic acids through that same process. Over the last decade, the emergence of Molecular Pathology, which benefits from gentler fixation compared to Histopathology and especially Immunohistopathology, has led to changes in how FFPETs are prepared. However, the remnant FFPETs from over a decade ago may be far from representative of what is now prepared for Molecular Pathology by many laboratories. Here we discuss our optimization of FFPET extraction for gently fixed samples. When we prepared our Seraseq FFPE Homologous Recombination Deficiency (HRD) reference standards using fixation conditions that are recommended for Molecular Pathology and extracted the resulting FFPETs using generic conditions, our initial coverage data from Whole Genome Shotgun (WGS) sequencing was difficult to analyze for changes in copy number across the genome. A major contributor to nonuniform coverage was identified as the formalin reversal step, where deparaffinized proteinase K-digested tissue is heated in water to near boiling to attempt to detach formaldehyde from nucleic acids through hydrolysis. Given the gentler fixation conditions, this step was found to be mostly unnecessary, and omitting it improved the resulting data substantially. A reason for this appears to be that the gentler fixation conditions that are now in use may not protect the DNA from the effects of near-boiling water, where the lack of salt lowers the melting temperature of double stranded DNA fragments and causes them to denature unless they have a higher GC content. Different kits used for the extraction of nucleic acids from FFPETs may benefit from different optimizations to obtain improved sequencing data from today’s Molecular pathology samples, and reference standards that represent such samples provide a useful tool for such optimizations. Citation Format: Matthew G. Butler, Benedicta Forson, Maria Cowen, Jayanthi Ramprakash, Dana Ruminski Lowe, Yves Konigshofer. The importance of optimizing DNA extraction conditions for formalin fixed paraffin embedded tissues [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3760.

5-Chloro-2'-deoxycytidine Induces a Distinctive High-Resolution Mutational Spectrum of Transition Mutations In Vivo.

The biomarker 5-chlorocytosine (5ClC) appears in the DNA of inflamed tissues. Replication of a site-specific 5ClC in a viral DNA genome results in C → T mutations, which is consistent with 5ClC acting as a thymine mimic in vivo. Direct damage of nucleic acids by immune-cell-derived hypochlorous acid is one mechanism by which 5ClC could appear in the genome. A second, nonmutually exclusive mechanism involves damage of cytosine nucleosides or nucleotides in the DNA precursor pool, with subsequent utilization of the 5ClC deoxynucleotide triphosphate as a precursor for DNA synthesis. The present work characterized the mutagenic properties of 5ClC in the nucleotide pool by exposing cells to the nucleoside 5-chloro-2'-deoxycytidine (5CldC). In both Escherichia coli and mouse embryonic fibroblasts (MEFs), 5CldC in the growth media was potently mutagenic, indicating that 5CldC enters cells and likely is erroneously incorporated into the genome from the nucleotide pool. High-resolution sequencing of DNA from MEFs derived from the gptΔ C57BL/6J mouse allowed qualitative and quantitative characterization of 5CldC-induced mutations; CG → TA transitions in 5'-GC(Y)-3' contexts (Y = a pyrimidine) were dominant, while TA → CG transitions appeared at a much lower frequency. The high-resolution mutational spectrum of 5CldC revealed a notable similarity to the Catalogue of Somatic Mutations in Cancer mutational signatures SBS84 and SBS42, which appear in human lymphoid tumors and in occupationally induced cholangiocarcinomas, respectively. SBS84 is associated with the expression of activation-induced cytidine deaminase (AID), a cytosine deaminase associated with inflammation, as well as immunoglobulin gene diversification during antibody maturation. The similarity between the spectra of AID activation and 5CldC could be coincidental; however, the administration of 5CldC did induce some AID expression in MEFs, which have no inherent expression of its gene. In summary, this work shows that 5CldC induces a distinct pattern of mutations in cells. Moreover, that pattern resembles human mutational signatures induced by inflammatory processes, such as those triggered in certain malignancies.

Catalytic nanomedicine for chronic wounds in diabetic patients: physiology, pathophysiology, and a success story

Chronic wounds, especially in diabetes patients, severely impact quality of life. Catalytic Nanomedicine offers hope by designing bionanocatalysts, nanostructures that selectively damage nucleic acids. These nanostructures excel in disinfection, harming microorganisms while preserving healthy tissue. They've been used for chronic wound healing, and this study explores their mechanisms and potential in tissue regeneration. The article underscores their significance in broad-spectrum disinfection, even against biofilms. It provides context by comparing glucose regulation in both healthy and diabetic states, with a focus on diabetic foot pathology. Lastly, it highlights a successful case of a diabetic chronic wound treated with Catalytic Nanomedicine to demonstrate its efficacy in promoting wound healing.

Deoxyribose Nucleic Acid Damage and Its Association With Plasma Malondialdehyde Levels Among Patients With Cervical Cancer: A Case-Control Study.

Purpose The objective of this research project was to estimate DNA damage in patients diagnosed with cervical cancer using the comet assay, establish a correlation between this quantification and the oxidative stress marker malondialdehyde (MDA; plasma MDA), and compare the resulting parameters between the cases and age-matched controls. Materials and methods This study included 49 cervical cancer cases and 49 age-matched controls to measure DNA damage parameters such as comet length, head diameter, percentage of DNA in the comet head, tail length, percentage of DNA in the comet tail, and oxidative stress marker (plasma MDA) using the thiobarbituric acid reactive substance (TBARS) enzyme-linked immunosorbent assay (ELISA) method. Results Comet metrics suggesting DNA damage, such as comet length, tail length, and percentage of DNA in the comet tail, were considerably higher in cervical cancer cases than in age-matched controls. The proportion of DNA in the comet head, representing undamaged/mild DNA damage, was significantly higher in age-matched controls than in cervical cancer patients. Plasma MDA and comet tail length were shown to have a positive correlation. Compared to the age-matched controls, those between the ages of 30 and 39, with a parity of two to four, who had a history of early age at first pregnancy and a positive family history of cervical cancer, had the highest level of DNA damage. Conclusion The elevated levels of comet parameters and their positive correlation with plasma MDA suggest that individuals diagnosed with cervical cancer have a higher degree of DNA damage compared to the control group. In conjunction with established methods like the PAP smear, this predictive test comprising comet assay and estimation of plasma MDA may be utilized to identify and assess the risk of cervical cancer in individuals aged 30-39 years, with a parity between two and four pregnancies and a prior history of early age at first pregnancy, accompanied by a positive family history of the disease.

Virus-like damaged nucleic acids are important causative agents and therapeutic targets in sporadic Alzheimer's disease

Virus-like damaged nucleic acids are important causative agents and therapeutic targets in sporadic Alzheimer's disease

DNA lesions triggered by visible light in skin cells: In the search for comprehensive sun protection

Skin cells present many endogenous photosensitizers (ePS) that interact with light, generating oxidizing species, causing molecular damage in proteins, lipids, and nucleic acids, and consequently triggering cellular and organelle malfunction. Several cell lines with terminal differentiation are susceptible to accumulating non-digestible pigments, such as lipofuscin or melanin-lipofuscin. Besides being hallmarks of aging, both pigments can work as photosensitizers, increasing and expanding the toxicity of sunlight to the range of visible light (VL, 400–700 nm). In here we review the literature to describe the mechanisms by which the photosensitized oxidation reactions induced by VL cause DNA damage. We aim to provide the mechanistic background needed to improve the current strategies of photoprotection.

Could Bioluminescent Bacteria be Used in the Search for New Plant-derived Antibacterial Substances?

Introduction. Currently, the search for new antibacterial substances is an urgent task due to the growing resistance of pathogens to existing antibiotics. One of the key directions in this area is the expansion of scientific research of medicinal plants, as new sources of therapeutic agents. This article examines the possibility of using highly sensitive bioluminescent test bacteria for these purposes, which can quickly detect non-specific antimicrobial activity and can be adapted to highly effective pharmaceutical screening technologies.Aim. To study the applicability of bioluminescent bacteria for the analysis of the antibacterial activity of biologically active substances (BAS) of plant origin.Materials and methods. BAS quercetin, 8-hydroxyquinoline, gallic acid and thymoquinone, which are often found in medicinal plant raw materials and with which its antibacterial properties are associated, were used in the work. Bacteria with constitutive bioluminescence Aliivibrio fischeri F1 and Escherichia coli (pXen7), as well as recombinant bioreporter strains with inducible luminescence were used as test-objects: E. coli (pRecA-lux), E. coli (pColD-lux), reacting to nucleic acid damage; E. coli (pKatG-lux) and E. coli (pSoxS-lux), sensitive to oxidative stress.Results and discussion. It was found that the nonspecific antimicrobial activity of the studied BAS is manifested in the inhibition of bacterial bioluminescence of test-strains with constitutive glowing. It was noted that the marine test-bacteria A. fischeri F1 have significantly greater sensitivity to the action of BAS, compared with the recombinant strain of E. coli (pXen7). It has been shown that their inhibitory effect begins at concentrations of 2 mcg/ml, and bactericidal activity occurs at concentrations of more than 20 mcg/ml. The results obtained are compared with the data on MIC and MBC of gram(+) and gram(–) pathogens. The study of the induction of bioluminescence of recombinant bioreporter strains showed that the antibacterial effect of the BAS is accompanied by oxidative stress. Also, quercetin caused activation of luminescence in E. coli (pRecA-lux) and E. coli (pColD-lux), which may indicate its participation in damage to nucleic acids. Analysis of the induction factors of bioreporter strains indicates that the revealed mechanisms of antibacterial activity are not major, but may be of a secondary nature.Conclusion. It has been shown that the intensity of the glow of natural and recombinant bioluminescent bacteria can be an indicator of the antibacterial activity of BAS of natural origin. The high sensitivity of A. fischeri F1 bacteria to the action of substances such as quercetin, 8-hydroxyquinoline, gallic acid and thymoquinone has been shown. Considering that bioluminescence analysis is a quantitative instrumental method, it can be easily adapted for high-throughput pharmaceutical screening. It has been shown that the luminescence intensity of natural and recombinant bioluminescent bacteria can be an indicator of the antibacterial activity of BAS of natural origin. The high sensitivity of A. fischeri F1 to the action of substances such as quercetin, 8-hydroxyquinoline, gallic acid and thymoquinone has been established. Taking in an account that bioluminescent analysis is a quantitative instrumental method, it can be easily adapted for high-throughput pharmaceutical screening.

Exoribonuclease RNase R protects Antarctic Pseudomonas syringae Lz4W from DNA damage and oxidative stress.

Bacterial exoribonucleases play a crucial role in RNA maturation, degradation, quality control, and turnover. In this study, we have uncovered a previously unknown role of 3'-5' exoribonuclease RNase R of Pseudomonas syringae Lz4W in DNA damage and oxidative stress response. Here, we show that neither the exoribonuclease function of RNase R nor its association with the RNA degradosome complex is essential for this function. Interestingly, in P. syringae Lz4W, hydrolytic RNase R exhibits physiological roles similar to phosphorolytic 3'-5' exoribonuclease PNPase of E. coli. Our data suggest that during the course of evolution, mesophilic E. coli and psychrotrophic P. syringae have apparently swapped these exoribonucleases to adapt to their respective environmental growth conditions.

Centrosomal protein of 192 kDa (Cep192) fragment possesses bactericidal and parasiticidal activities in Larimichthys crocea

A novel AMP Lc1773, derived from centrosomal protein of 192 kDa (Cep192), was isolated from Larimichthys crocea using a Bacillus subtilis system. After cDNA libraries construction, repeating selection of B. subtilis system, extraction of extracellular protein, and expression of recombinant protein, we found that B. subtilis 1773, extracellular protein, and rLc1773 had a strong potential to kill Vibrio. parahaemolyticus and V. vulnificus. Further analysis of the antibacterial mechanism revealed that rLc1773 not only disrupted the integrity of bacterial membrane (as confirmed by SEM, TEM, and confocal microscopy observation, and flow cytometry assays), resulting in bacterial cell membrane pore conformation, bacterial rupture, and leakage of cellular contents, but also targeted to block protein synthesis rather than damage nucleic acids (as confirmed by SDS-PAGE, enzyme expression, and gel retardation assays). In addition, rLc1773 had the ability to kill parasite Scuticociliatida in a high rate and low concentration. Critically, the antibacterial activity of rLc1773 had good thermal stability and UV radiation tolerance, but it was affected by pH 9–11 and diverse enzyme to some extent. Lc1773 had neither hemolysis on fish, shrimp, and rabbit erythrocytes，nor significant cytotoxicity. To our knowledge, Cep192 fragment was first demonstrated to possess bactericidal and parasiticidal activities.

Recent advances and future directions in etiopathogenesis and mechanisms of reactive oxygen species in cancer treatment.

A class of exceptionally bioactive molecules known as reactive oxygen species (ROS) have been widely studied in the context of cancer. They play a significant role in the etiopathogenesis for cancer. Implication of ROS in cancer biology is an evolving area, considering the recent advances; insights into their generation, role of genomic and epigenetic regulators for ROS, earlier thought to be a chemical process, with interrelations with cell death pathways- Apoptosis, ferroptosis, necroptosis and autophagy has been explored for newer targets that shift the balance of ROS towards cancer cell death. ROS are signal transducers that induce angiogenesis, invasion, cell migration, and proliferation at low to moderate concentrations and are considered normal by-products of a range of biological activities. Although ROS is known to exist in the oncology domain since time immemorial, its excessive quantities are known to damage organelles, membranes, lipids, proteins, and nucleic acids, resulting in cell death. In the last two decades, numerous studies have demonstrated immunotherapies and other anticancer treatments that modulate ROS levels have promising in vitro and in vivo effects. This review also explores recent targets for therapeutic interventions in cancer that are based on ROS generation or inhibition to disrupt the cell oxidative stress balance. Examples include-metabolic targets, targeted therapy with biomarkers, natural extracts and nutraceuticals and targets developed in the area of nano medicine. In this review, we present the molecular pathways which can be used to create therapy plans that target cancer by regulating ROS levels, particularly current developments and potential prospects for the effective implementation of ROS-mediated therapies in clinical settings. The recent advances in complex interaction with apoptosis especially ferroptosis and its role in epigenomics and modifications are a new paradigm, to just mechanical action of ROS, as highlighted in this review. Their inhibition by nutraceuticals and natural extracts has been a scientific challenging avenue that is explored. Also, the inhibition of generation of ROS by inhibitors, immune modulators and inhibitors of apoptosis and ferroptosis is explored in this review.

A-040 Night Shift Work Could Induce Oxidatively Generated Damage to DNA: A Pilot Study

Abstract Background Currently, specific effects of different night shift modes on human oxidative stress still need to be explored in a realistic cohort study. We aimed to evaluate the effect of night shift on human nucleic acid damage status. Methods We recruited 16 healthy volunteers (aged, 33 ± 5 years) working the night shifts at the Department of Laboratory Medicine at Peking Union Medical College Hospital. Their matched serum and urine samples were collected at four time points: before, during (twice), and after the night shift period. The levels of 8-oxo-7,8-dihydroguanosine (8-oxoG) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), two important nucleic acid damage markers, were accurately determined based on a robust self-established LC-MS/MS method. The Mann–Whitney U or Kruskal-Wallis test was used for comparisons. Results The levels of serum 8-oxodG, estimated glomerular filtration rate corrected serum 8-oxodG, and 8-oxodG in serum to urine ratio significantly increased during the night shift period. These levels were significantly higher than at baseline even after 1 month of discontinuing; but no such significant change was found for 8-oxoG. Moreover, 8-oxoG and 8-oxodG levels revealed a significantly positive association with many routine biomarkers such as total bilirubin and urea levels, and significantly negative association with serum lipids such as total cholesterol levels. Conclusion The results of our cohort study suggested that working the night shifts may increase the oxidatively generated damage to DNA even after a month of discontinuing night shift work. Further studies with large-scale cohorts, different night shift modes, and longer follow-up times are needed to clarify the short- and long-term effect of night shifts on DNA damage, and find effective solutions to combat the negative effects.

Role of Melatonin in Directing Plant Physiology

Melatonin (MT), a naturally occurring compound, is found in various species worldwide. In 1958, it was first identified in the pineal gland of dairy cows. MT is an “old friend” but a “new compound” for plant biology. It brings experts and research minds from the broad field of plant sciences due to its considerable influence on plant systems. The MT production process in plants and animals is distinct, where it has been expressed explicitly in chloroplasts and mitochondria in plants. Tryptophan acts as the precursor for the formation of phyto-melatonin, along with intermediates including tryptamine, serotonin, N-acetyl serotonin, and 5-methoxy tryptamine. It plays a vital role in growth phases such as the seed germination and seedling growth of crop plants. MT significantly impacts the gas exchange, thereby improving physio-chemical functions in plant systems. During stress, the excessive generation and accumulation of reactive oxygen species (ROS) causes protein oxidation, lipid peroxidation, nucleic acid damage, and enzyme inhibition. Because it directly acts as an antioxidant compound, it awakens the plant antioxidant defense system during stress and reduces the production of ROS, which results in decreasing cellular oxidative damage. MT can enhance plant growth and development in response to various abiotic stresses such as drought, salinity, high temperature, flooding, and heavy metals by regulating the antioxidant mechanism of plants. However, these reactions differ significantly from crop to crop and are based on the level and kind of stress. The role of MT in the physiological functions of plants towards plant growth and development, tolerance towards various abiotic stresses, and approaches for enhancing the endogenous MT in plant systems are broadly reviewed and it is suggested that MT is a steering compound in directing major physiological functions of plants under the changing climate in future.

The study on the residential radon concentration in the rooms in the areas of the Republic of Moldova

Natural radioactivity is still a topic addressed at the international level with multiple segments interspersed in the upward pace of technological and economic development at the local level. The intensity of concerns in the aspect of radioprotection starts from a series of factors that condition the level and doses of exposure of the population to sources of ionizing radiation, thus determining the medical, social, economic and demographic effects in the characteristic of a medico-social problem. Radon, through its contribution to the creation of the natural radioactive background, has a crucial role in the etiology of oncological diseases of broncho-pulmonary origin, leukemias and other pathologies. Long-term exposure to increased concentrations of radon and the association of other risk factors, such as tobacco consumption, causes the alteration of cellular metabolism processes, the damage of DNA and RNA nucleic acids, the formation of free radicals and the appearance of mutations that can constantly trigger lung cancer. The continuous monitoring of residential radon concentrations is a primary objective within the strategy to control and reduce the long-term negative effects of radon, being a main element of the action plan of the EURATOM Directive 59/2013.

Alzheimer's Disease and Green Tea: Epigallocatechin-3-Gallate as a Modulator of Inflammation and Oxidative Stress.

Alzheimer's disease (AD) is the most common cause of dementia, characterised by a marked decline of both memory and cognition, along with pathophysiological hallmarks including amyloid beta peptide (Aβ) accumulation, tau protein hyperphosphorylation, neuronal loss and inflammation in the brain. Additionally, oxidative stress caused by an imbalance between free radicals and antioxidants is considered one of the main risk factors for AD, since it can result in protein, lipid and nucleic acid damage and exacerbate Aβ and tau pathology. To date, there is a lack of successful pharmacological approaches to cure or even ameliorate the terrible impact of this disease. Due to this, dietary compounds with antioxidative and anti-inflammatory properties acquire special relevance as potential therapeutic agents. In this context, green tea, and its main bioactive compound, epigallocatechin-3-gallate (EGCG), have been targeted as a plausible option for the modulation of AD. Specifically, EGCG acts as an antioxidant by regulating inflammatory processes involved in neurodegeneration such as ferroptosis and microglia-induced cytotoxicity and by inducing signalling pathways related to neuronal survival. Furthermore, it reduces tau hyperphosphorylation and aggregation and promotes the non-amyloidogenic route of APP processing, thus preventing the formation of Aβ and its subsequent accumulation. Taken together, these results suggest that EGCG may be a suitable candidate in the search for potential therapeutic compounds for neurodegenerative disorders involving inflammation and oxidative stress, including Alzheimer's disease.