Destruction Of DNA Research Articles

The assessment of aristida adscensionis and rumex hypogaeus comparative and combine antioxidant potential

Exogenous substances and cellular metabolism both produce free radicals in cells. The produced free radicals react with cell biomolecules, including DNA. The ensuing destruction of DNA, also known as oxidative DNA damage, which is connected to aging, carcinogenesis, and mutagenesis. The Aristida adscensionis plays an essential role in the modulation of free radicals. We examined the antioxidant therapy of individual or combined forms of the Aristida adscensionis and Rumex hypogaeus plant extracts. We noticed that Aristida adscensionis showed scavenging activity at various concentrations i.e. 50, 100, 250, 500, and 1000 ?g/ml was 42%, 50%, 62%, 69% and 75% respectively. The scavenging activity of Rumex hypogaeus at various concentrations was 43%, 52%, 58%, 66% and 75% against the standard of ascorbic acid. We noticed that the combined mixture of both plant extracts elucidated a significant antioxidant potential at different concentrations of 100 ?g/ml, 500 ?g/ml, and 1000 ?g/ml which were 58%, 70%, 74%, 81% and 86 %. Our research study demonstrates that combinaion of both plants' extract mixtures had a more substantial antioxidant capacity than each extract individually. This property of these plants can be used for cancer treatment, however further robust data is required.

Bleomycin‐dependent DNA damage, erythrocyte hemolysis, antitumor MTT assay, and antimicrobial activity studies for Cd (II), Mn (II), Zn (II), Cr (III), and Fe (III) complexes of a multidentate carbohydrazone ligand

Cd (II), Mn (II), Zn (II), Cr (III), and Fe (III) complexes of a carbohydrazone ligand H4EBC, prepared by the reaction of ethyl acetate and carbohydrazide, have been prepared and fully characterized. The ligand H4EBC acted as a bidentate carbohydrazone with Cd (II) and coordinated through the nitrogen of both (‐NH) and (C=N)azomethine groups, while with Mn (II) and Zn (II), it acted as a neutral NN bidentate ligand. In complexes with Fe (III) and Cr (III), H4EBC acts a bi‐negative tetra‐dentate, coordinating through the oxygen atoms of both enolized (C=O)ester groups and the nitrogen of both (C=N)azomethine groups. To illustrate the proposed geometries and chemical reactivity of the compounds, we employed DFT calculations. Additionally, thermal studies provided insights into the stability of the isolated compounds. Interestingly, the prepared complexes demonstrated emission broad bands at various wavelengths, indicating ligand to metal charge transfer. Based on the inhibition of DNA destruction, the complexes can be ranked in the following order: [Cd(H4EBC)Cl2].2H2O] (1) > H4EBC > [Mn(H4EBC)Cl2)].(H2O)2] (2) > [Zn(H4EBC)Cl2].2H2O] (3) > [Fe(H2EBC)Cl(H2O)].H2O (5) > [Cr(H2EBC)Cl (H2O)].H2O (4). Regarding erythrocyte hemolysis, the order of effectiveness can be arranged as follows: (2) > (1) > H4EBC > (5) > (3) > (4). We further investigated the compounds for their potential in antitumor activity against two cell lines and antimicrobial behavior.

REVIEW OF PHYTO-MEDICAL EXTRACTS’ AND COMPOUNDS’ ANTI-RADIATION PROPERTIES

Humans are routinely exposed to radiation when receiving cancer treatment, fighting nuclear weapons, exploring space, and flying. Radiation exposure damages biological components such as protein, lipids, and cell membranes because it causes oxidative stress and inflammatory mediators, which can lead to DNA destruction even at low concentrations. Protecting people from the harmful effects of radiation is a challenging task due to the plethora of side effects of the chemical compounds used to mitigate DNA damage in normal cells. Hospitals continue to utilize radiotherapy for cancer treatment; yet, the adverse effects of the radiation they emit have outweighed the benefits. Plant phytochemicals and their derivatives exhibit diverse biological functions, often perceived as innocuous due to their non-toxic nature within subcellular and cellular environments. Moreover, they possess the capability to mitigate radiation-induced damage. This review aims to delineate the radioprotective attributes of plant polyphenols and extracts, elucidating their mechanisms of action across various models.

Evaluation of phytotoxicity, biochemical profiles, bioaccumulation hazard, and toxicity implications of battery manufacturing industrial discharge using a soilless cultivation system

This study has been devoted to the compositional evaluation of battery manufacturing industrial discharge (ID) and comprehensive assessment of: (i) plant vigor, chlorophylls contents, oxidative stress biomarkers; (ii) antioxidant defense system; (iii) non-enzymatic antioxidant responses; (iv) bioaccumulative profiles of toxic pollutants; and (v) in vitro genotoxicity and cytotoxicity of the four weeks ID-irrigated Ipomoea aquatica. Pb was identified as the dominating pollutant (5.35 mg/L) in the ID, with the accumulative profiles ranging from 0.002 to 1.36 mg/kg dry weight, in the descending order of root > shoot > leaf within Ipomoea aquatica. Profound inhibition of roots (26.60%) and shoots growth (20.53%), reduction of chlorophylls contents (39.81%), excessive-generation of superoxide anion (53.33%), hydrogen peroxide (55%), and lipid peroxidation (26.15%) were recorded. Antioxidant enzymes were up-regulated while the ferric reducing antioxidant power and radicals scavenging activities were concurrently enhanced. The in vitro toxicity of ID was verified by the significant dose-dependent increase in the mitochondrial respiratory inhibition associated-cell death and DNA destruction in the HepG2 cell (p < 0.05). These acquired findings have signified the threatening implications of Pb-contaminated ID-assisted irrigation on the sustainability of environmental and public health, and food security management.

Abstract 7025: Advancing methylation analysis: TAPS v1.0: A fast, scalable, and non-destructive sequencing method

Abstract In the pursuit of advancing multi-cancer early detection, the exploration of cell-free DNA (cfDNA) through methylation profiling has emerged as a promising avenue. However, the realization of its full potential is impeded by limitations inherent in conventional methodologies, notably the 'gold standard' bisulfite conversion methods. These approaches pose challenges such as DNA destruction and the generation of low-complexity sequences resulting from the conversion of unmethylated cytosines to thymine. TET Assisted Pyridine-Borane Sequencing (TAPS) holds the potential as a non-destructive, rapid, and scalable alternative for base-level methylation analysis. In this context, we introduce TET Assisted Pyridine-Borane Sequencing version 1.0 (TAPS v1.0), showcasing advancements to the technology originally introduced by Schuster-Böckler, Song, and their collaborators. TAPS v1.0 transforms 5mC into dihydrouracil (DHU) through a series of oxidation and reduction reactions. Ultimately, DHU is recognized as dU during PCR resulting in C-to-T conversions at 5mC sites, leaving unmethylated cytosines, the majority of cytosines, unchanged. The nondestructive nature of 5mC conversion yields significantly higher library yield and complexity compared to BS-seq. By leveraging Watchmaker's proprietary polymerase evolution platform, a DNA polymerase tolerant to DHU was selected for library amplification post DHU conversion, enabling unimpeded detection of 5mC, particularly in densely packed CpG repeats. Coupled with an optimized End Repair and A-tailing chemistry preceding TAPS v1.0, clinically relevant cfDNA samples of low quality and/or quantity can be analyzed in methylation detection pipelines. To evaluate the performance of TAPS v1.0, human genomic DNA with control spike-ins featuring varying methylation statuses were employed. TAPS v1.0 exhibited significantly higher final library yield and greater complexity compared to BS-seq. Similar outcomes were observed in clinically relevant cfDNA samples. Citation Format: Josh Haimes, Craig Marshall, Travis Sanders, Sam Vogel, Martin Ranik, Eduard Casas, Doug Wendel, Leo Karamanof, Bjarne Faurholme, Abre de Beer, Lee French, Ross Wadsworth, Kristina Giordia, Eric van der Walt, Brian Kudlow. Advancing methylation analysis: TAPS v1.0: A fast, scalable, and non-destructive sequencing method [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 7025.

Induction of Gynogenetic Diploids the Tropical Oyster, Crassostrea belcheri 1873 (Ostreids: Ostreoidea)

The induction of diploid gynogenesis in the Tropical oyster, Crassostrea belcheri 1873, was carried out through two main experiments: 1) the destruction of spermatozoa DNA using ultraviolet (UV) irradiation, and 2) the induction of gynogenetic diploids. UV light source was placed 30 cm over the sperm for various durations, including 0 (control), 30, 60, 90, and 120 seconds. The study revealed that the highest survival rate was observed in trochophore at 90 minutes (42.5 ± 2.50%) compared to the normal control C. belcheri (p&gt;0.05). Based on cytogenetic study, haploid (n=10), diploid (2n=20), and aneuploid were observed in all trials, while only diploid (2n=20) could be seen in the control group. Diploid gynogenesis was induced using 100 µmol 6-DMAP for 10 minutes. The study found that the survival rate and developmental stages in both trochophore and D-shape were gradually decreasing as the duration of UV rays increased. The highest survival rate of trochophore in the control group was 75.20 ± 4.84%, while survival rates in other experimental groups ranged from 52.22 ± 4.82% to 59.33 ± 13.57%. However, regarding the survival rate of D-shape larvae, their survival rates were relatively low across all trials. They displayed abnormal embryo development, distorted shape, unnatural swimming, and were smaller than normal (40-50 µm). Moreover, haploid (n=10), diploid (2n=20), triploid (3n=30), tetraploid (4n=40), and aneuploid were observed in all trials, while only diploid (2n=20) could be discovered in the control group. However, gynogenesis in this tropical oyster is still limited at this time. Therefore, suitable conditions for inducing gynogenesis in oysters should be further developed.

Retention of the RNA ends provides the molecular memory for maintaining the activation of the Csm complex.

The type III CRISPR-Cas effector complex Csm functions as a molecular Swiss army knife that provides multilevel defense against foreign nucleic acids. The coordinated action of three catalytic activities of the Csm complex enables simultaneous degradation of the invader's RNA transcripts, destruction of the template DNA and synthesis of signaling molecules (cyclic oligoadenylates cAn) that activate auxiliary proteins to reinforce CRISPR-Cas defense. Here, we employed single-molecule techniques to connect the kinetics of RNA binding, dissociation, and DNA hydrolysis by the Csm complex from Streptococcus thermophilus. Although single-stranded RNA is cleaved rapidly (within seconds), dual-color FCS experiments and single-molecule TIRF microscopy revealed that Csm remains bound to terminal RNA cleavage products with a half-life of over 1 hour while releasing the internal RNA fragments quickly. Using a continuous fluorescent DNA degradation assay, we observed that RNA-regulated single-stranded DNase activity decreases on a similar timescale. These findings suggest that after fast target RNA cleavage the terminal RNA cleavage products stay bound within the Csm complex, keeping the Cas10 subunit activated for DNA destruction. Additionally, we demonstrate that during Cas10 activation, the complex remains capable of RNA turnover, i.e. of ongoing degradation of target RNA.

A TME-activated nano-catalyst for triple synergistic therapy of colorectal cancer

Colorectal cancer cells are highly heterogeneous and exhibit various drug resistances, making personalized treatment necessary. This typically involves a combination of different treatment modalities such as surgery, radiation, and chemotherapy to increase patient survival. Inspired by this, synergistic therapy, which combines multiple modalities into a single nanotherapeutic drug, shows promise in treating cancer. In this study, a nano-catalyst based on calcium peroxide (CaO2) and the chemotherapeutic drug doxorubicin hydrochloride (DOX) co-loaded into HPB nanoparticles (HPB@CaO2/DOX-PAA) was developed to achieve synergistic cancer treatment through chemodynamic/chemo/photothermal (CDT/CT/PTT) mechanisms. After being endocytosed by cancer cells, the nano-catalyst decomposes, releasing cargo. During near-infrared light irradiation, HPB induces a photothermal effect, DOX exhibits significant RNA and DNA destruction capabilities, meanwhile CaO2 produces a large amount of H2O2 in the moderately acidic TME, which combines with Fe2+ ions derived from HPB to form the highly toxic •OH in a Fenton-like reaction, enhancing the chemodynamic treatment. Assays conducted ex vivo and in vivo have exhibited the efficacy of this triple synergistic therapeutic regimen, indicating its potential clinical application.

Activation of CBASS Cap5 endonuclease immune effector by cyclic nucleotides.

The bacterial cyclic oligonucleotide-based antiphage signaling system (CBASS) is similar to the cGAS-STING system in humans, containing an enzyme that synthesizes a cyclic nucleotide on viral infection and an effector that senses the second messenger for the antiviral response. Cap5, containing a SAVED domain coupled to an HNH DNA endonuclease domain, is the most abundant CBASS effector, yet the mechanism by which it becomes activated for cell killing remains unknown. We present here high-resolution structures of full-length Cap5 from Pseudomonas syringae (Ps) with second messengers. The key to PsCap5 activation is a dimer-to-tetramer transition, whereby the binding of second messenger to dimer triggers an open-to-closed transformation of the SAVED domains, furnishing a surface for assembly of the tetramer. This movement propagates to the HNH domains, juxtaposing and converting two HNH domains into states for DNA destruction. These results show how Cap5 effects bacterial cell suicide and we provide proof-in-principle data that the CBASS can be extrinsically activated to limit bacterial infections.

Toxicity of Polymeric Nanodrugs as Drug Carriers

The ambiguity of certain diseases and the potential toxicity of many medications have sparked demand for the incorporation and enhancement of drug delivery systems (DDSs). Nanomedicine has received renewed attention in modern medical advancements with therapeutic uses. Therefore, the development of nanomedicines for enhanced bioaccessibility, long drug administration, and dose reduction has advanced as a unique concept. Nanocapsules, nanoemulsions, drug nanocrystals, micelles, solid lipid nanoparticles (SLNs), and polymeric nanoparticles (poly-NPs) are among the most effective nanomedicine techniques. Poly-NPs have emerged as a potential method to enhance drug pharmacokinetics. Pharmaceutical potency can be increased by using nanocarriers and medication formulations. The potential of poly-NPs to alter contemporary medicine has attracted significant interest; polymer adaptability makes them suitable for site-specific drug delivery requirements. However, little is known about their safety in long-term studies using high-pitched doses. These cells exhibit some extrapyramidal symptoms (EPS) because of the reactivity and size reduction of the polymers chosen by using living cells other than the target. With an increased understanding of polymers and their properties, it is equally important to emphasize the safety and toxicity of DDSs. Some of the toxic effects of polymeric nanodrugs include an increase in the cytotoxicity of the cell, reduction in the feasibility of the cell, increase in the rate of programmed cell death (apoptosis), precursors for tumor formation, DNA destruction, gene toxicity, rupture of the cell membrane, and lipid peroxidation reactions. In this article, we discuss the toxicity of nanoparticles (NPs) used in DDSs, including polylactide-co-glycolide, polylactic acid, polycaprolactone, and poly(alkyl cyanoacrylates), used in DDSs.

Probiotic Lactobacillus Species and Their Biosurfactants Eliminate Acinetobacter baumannii Biofilm in Various Manners.

Acinetobacter baumannii is a critical biofilm-forming pathogen that has presented great challenges in the clinic due to multidrug resistance. Thus, new methods of intervention are needed to control biofilm-associated infections. In this study, among three tested Lactobacillus species, Lactobacillus rhamnosus showed significant antimaturation and antiadherence effects against A. baumannii biofilm. Lactic acid (LA) and acetic acid (AA) were the most effective antibiofilm biosurfactants (BSs) produced by L. rhamnosus. This antibiofilm phenomenon produced by LA and AA was due to the strong bactericidal effect, which worked from very early time points, as determined by colony enumeration and confocal laser scanning microscope. The cell destruction of A. baumannii appeared in both the cell envelope and cytoplasm. A discontinuous cell envelope, the leakage of cell contents, and the increased extracellular activity of ATPase demonstrated the disruption of the cell membrane by LA and AA. These effects also demonstrated the occurrence of protein lysis. In addition, bacterial DNA interacted with and was damaged by LA and AA, resulting in significantly reduced expression of biofilm and DNA repair genes. The results highlight the possibility and importance of using probiotics in clinical prevention. Probiotics can be utilized as novel biocides to block and decrease biofilm formation and microbial contamination in medical equipment and during the treatment of infections. IMPORTANCE A. baumannii biofilm is a significant virulence factor that causes the biofilm colonization of invasive illnesses. Rising bacterial resistance to synthetic antimicrobials has prompted researchers to look at natural alternatives, such as probiotics and their derivatives. In this study, L. rhamnosus and its BSs (LA and AA) demonstrated remarkable antibiofilm and antimicrobial characteristics, with a significant inhibitory effect on A. baumannii. These effects were achieved by several mechanisms, including the disruption of the cell envelope membrane, protein lysis, reduced expression of biofilm-related genes, and destruction of bacterial DNA. The results provide support for the possibility of using probiotics and their derivatives in the clinical prevention and therapy of A. baumannii infections.

Enhancement of photocatalytic-based processes by mono- and bimetallic (CuPd) rutile loaded nanoparticles for antibiotic resistance genes and facultative pathogenic bacteria removal

The aim of the study was the strong reduction of facultative pathogenic bacteria (FPB), and clinically relevant antibiotic resistance genes (ARGs) from secondary effluent. To evaluate the ARGs removal efficiency comparative study ofindividual unit processes and combined AOPs has been performed. The present work investigated: i) removal of selected ARGs, namely blaTEM, ermB, qnrS, tetM, five FPB as well as 16S rDNA and the integrase gene intl1 involved in horizontal gene transfer; ii) bacterial regrowth potential after treatment; (iii) the removal of the total genomic DNA content, by mono- and bimetallic TiO2-CuPd rutile photocatalysts under visible light radiation in real secondary effluent.The nanoparticles were characterized by UV–vis, XRD, HRTEM, Raman and XPS. TiO2-CuPd/VIS inactivation gives the highest (more than 2 log units removal) efficiency for almost all targets (blaTEM, ermB, tetM, intl 1, and 16S rRNA) compared to monometallic catalysts. The highest efficiency toward blaTEM was achieved after ozonation and TiO2-CuPd/O3/VIS (3.22 and 3.23 LRV, respectively). It was found that despite similar FPB inactivation, lower DNA destruction was found after O3 compared to TiO2-CuPd/O3/VIS treatment. The blaTEM and enterococci were completely removed during TiO2-CuPd/O3/Vis and TiO2-Cu/O3/Vis. While, catalytic ozonation leads to only slightly blaTEM removal (0.64 and 0.44 LRV for TiO2-CuPd/O3 and TiO2-Cu/O3, respectively). Photocatalytic ozonation with the application of TiO2-CuPd leads to significant removal of FPB and ARGs due to synergistic effect between Pd and Cu, which leads to acceleration of ozone – catalysts reaction. Photocatalytic ozonation has the greatest potential giving promising possibilities for eliminating AMR.

Mitochondrial DNA Enrichment for Sensitive Next-Generation Sequencing.

Mitochondrial DNA (mtDNA) encodes components essential for cellular respiration. Low levels of point mutations and deletions accumulate in mtDNA during normal aging. However, improper maintenance of mtDNA results in mitochondrial diseases, stemming from progressive loss of mitochondrial function through the accelerated formation of deletions and mutations in mtDNA. To better understand the molecular mechanisms underlying the creation and propagation of mtDNA deletions, we developed the LostArc next-generation DNA sequencing pipeline to detect and quantify rare mtDNA species in small tissue samples. LostArc procedures are designed to minimize PCR amplification of mtDNA and instead achieve enrichment of mtDNA by selective destruction of nuclear DNA. This approach leads to cost-effective, high-depth sequencing of mtDNA with a sensitivity sufficient to identify one mtDNA deletion per million mtDNA circles. Here, we describe detailed protocols for isolation of genomic DNA from mouse tissues, enrichment of mtDNA through enzymatic destruction of linear nuclear DNA, and preparation of libraries for unbiased next-generation sequencing of mtDNA.

Влияние длины молекул и природы среды на фрагментацию ДНК ультразвуком

Fragmentation of DNA by ultrasound is the most optimal method of artificial degradation of DNA molecules. It requires no reagents and makes it possible to obtain "pure" DNA samples for further use. However, despite an active usage of ultrasonic fragmentation in studies, a number of issues related to the applicability of mechanically degraded DNA for standard molecular biological operations remain poorly studied. This report presents data on the effect of the size of DNA molecules (on DNA amplicons) and the composition of aqueous solutions on the efficiency of DNA destruction by ultrasound. It has been shown that the rate of DNA fragmentation positively correlates with an increase in the length of molecules. In solutions with high ionic strength, the rate of fragmentation increases dramatically. The presence of organic solvents that do not affect hybridization slightly reduces the rate of ultrasonic destruction. With an increase in the length of DNA molecules, the influence of denaturing agents changes and leads to an increase in the rate of fragmentation. dsDNA molecules smaller than one persistent length (about 150 bp) are not fragmented.

Gallic acid a flavonoid isolated from Euphorbia hirta antagonizes gamma radiation induced radiotoxicity in lymphocytes in vitro.

The current study was executed to isolate and evaluate gallic acid from Euphorbia hirta for in vitro radioprotective potentials against gamma irradiation caused radiotoxicity in human lymphocytes. The defatted E.hirta plant material was treated to methanol extraction using the soxhlet device. Bioflavonoids were isolated from the E.hirta methanol extract using column chromatography. In human cells exhibited to gamma radiation, separated flavonoid gallic acid was examined for in vitro radioprotective potentials using the micronucleus test, DNA fragmentation assay, superoxide free radical scavenging method, and apoptic assay. The frequency of micronuclei was considerably declined when cells were preprocessed with gallic acid (25g/mL) before being exhibited to 2Gy gamma radiation, as determined by the cytokinesis blocked micronucleus test. Similarly, pre-gamma radiation treatment of human cells with gallic acid led in markedly less DNA injury, as assessed by comet metrics like olive tail moment and percent tail DNA. Gallic acid (25g/mL) given to lymphocytes prior to gamma irradiation considerably decreased the percentage of apoptotic bodies. Gallic acid also considerably lowered the reactive oxygen species concentrations elicited by gamma radiation. Our findings showed that gallic acid protects lymphocytes isolated from human blood from gamma radiation-induced DNA destruction and anti-apoptotic activity, which could be because of inhibition of free radicals formed by gamma radiation as well as the decline of gamma radiation-induced oxidative stress.

Structure and mechanism of the type I-G CRISPR effector.

Type I CRISPR systems are the most common CRISPR type found in bacteria. They use a multisubunit effector, guided by crRNA, to detect and bind dsDNA targets, forming an R-loop and recruiting the Cas3 enzyme to facilitate target DNA destruction, thus providing immunity against mobile genetic elements. Subtypes have been classified into families A-G, with type I-G being the least well understood. Here, we report the composition, structure and function of the type I-G Cascade CRISPR effector from Thioalkalivibrio sulfidiphilus, revealing key new molecular details. The unique Csb2 subunit processes pre-crRNA, remaining bound to the 3' end of the mature crRNA, and seven Cas7 subunits form the backbone of the effector. Cas3 associates stably with the effector complex via the Cas8g subunit and is important for target DNA recognition. Structural analysis by cryo-Electron Microscopy reveals a strikingly curved backbone conformation with Cas8g spanning the belly of the structure. These biochemical and structural insights shed new light on the diversity of type I systems and open the way to applications in genome engineering.

Carbonil stress parameters and DNA oxidative modification in Russian and Buryat women with age-related menopause

BACKGROUND: Menopause is a risk factor for oxidative stress. Previous study results indicate the lipid peroxidation ethnospecificity, suggesting differences in the metabolism of different ethnic groups of women, associated with the oxidation of not only lipids but proteins and DNA.&#x0D; AIM: To determine advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), and DNA oxidative modification levels in the blood of Russian and Buryat peri- and postmenopausal women.&#x0D; MATERIAL AND METHODS: The study involved 86 women of two ethnic groups Russians (n=52) and Buryats (n=34) aged 45 to 60 years with peri- and postmenopausal status, which participated as volunteers. The basis for the exclusion in this study was the use of hormone replacement therapy, antioxidant drugs, diseases of endocrine origin, exacerbation of chronic diseases, premature early menopause, and surgical menopause. The concentration of 8-hydroxy-2'-deoxyguanosine (ng/ml) and AGEs (ng/ml) was determined in blood serum by enzyme immunoassay. The content of AOPP (nmol/l) was determined in blood plasma using the photometric method.&#x0D; RESULTS: An increase of AOPP levels in postmenopause as compared to perimenopause was found in women of both ethnic groups (36.90 [27.09; 42.72] and 19.80 [17.03; 23.78] in the Russian ethnic group (p 0.001) and 31.16 [29.45; 33.99] and 26.30 [23.44; 30.91] in the Buryat ethnic group (p=0.020). Regardless of the menopausal phase, the AGEs levels in Buryat women were higher than the Russian ethnic group: (5015.0 [4584.49; 5486.96] and 3685.87 [3376.11; 4318.0] in perimenopause (p=0.002) and 4970 [4710; 5660] and 4274.59 [3440.67; 4813.05] in postmenopause (p=0.040)) and 8-hydroxy-2'-deoxyguanosine (1.58 [0.66; 4.36] and 0.82 [0.42; 1.09] in perimenopause (p=0.032) and 1.52 [1.06; 4.21] and 0.85 [0.49; 1.34] in postmenopause (p=0.018)). Differences in the AOPP level were revealed only in the perimenopause toward a higher level in Buryat women.&#x0D; CONCLUSION: Protein oxidation depends on the menopausal phase and is more pronounced in postmenopausal women. The carbonyl stress parameters and DNA destruction levels are higher in Buryat women than Russian ethnic group.

Reactive Nitrogen Species Mediated Inactivation of Pathogenic Microorganisms during UVA Photolysis of Nitrite at Surface Water Levels.

UVA photolysis of nitrite (NO2-) occurs in a number of natural and engineered aquatic systems. This study reports for the first time that pathogenic microorganisms can be effectively inactivated during the coexposure of UVA irradiation and NO2- under environmentally relevant conditions. The results demonstrated that more than 3 log inactivation of Escherichia coli K-12, Staphylococcus aureus, and Spingopyxis sp. BM1-1 was achieved by UVA photolysis of 2.0 mg-N L-1 of NO2- in synthetic drinking water and real surface water. The inactivation was mainly attributed to the reactive species generated from UVA photolysis of NO2- rather than UVA irradiation or NO2- oxidation alone. The inactivation was predominantly contributed by the reactive nitrogen species (NO2• and ONOO-/HOONO) instead of the reactive oxygen species (HO• or O2•-). A kinetic model to simulate the reactive species generation from UVA photolysis of NO2- was established, validated, and used to predict the contributions of different reactive species to the inactivation under various environmental conditions. Several advanced tools (e.g., D2O - labeling with Raman spectroscopy) were used to demonstrate that the inactivation by the UVA/NO2- treatment was attributed to the DNA destruction by the reactive nitrogen species, which completely suppressed the viable but nonculturable (VBNC) states and the reactivation of bacteria. This study highlights a novel process for the inactivation of pathogenic microorganisms in water and emphasizes the critical role of reactive nitrogen species in water disinfection and purification.

In vivo study of beta-glucan-based biogenic synthesis of silver nanocomposite using Schizophyllum commune for wound dressings in a rat burn model

Bacterial infection is a significant barrier to the natural wound healing process. Silver nanoparticles have antibacterial activity through the destruction of DNA and bacterial membranes. In the present study, a green method was introduced to synthesize silver nanoparticles produced by the Schizophyllum commune. The antibacterial mat loaded with 0.5, 1, and 3% (w/w) of bioactive silver nanoparticles were produced in polyvinyl alcohol (PVA) and schizophyllan (SPG) solution (20:80) with electrospun (PVA/SPG). Then the physicochemical properties of silver nanoparticles and the mats PVA/SPG containing silver nanoparticles were investigated. An animal model also examined antimicrobial activity, cytotoxicity, adhesion, and grade II burn ulcers. The results showed that spherical silver nanoparticles with a diameter of about 40 nm were produced and completely scattered on the nanofibers according to TEM images. A non-covalent interaction was revealed between SPG and AgNPs; the nanofibers were hydrophilic. Nanofibers containing silver nanoparticles had intense antimicrobial activity against E. coli and S. aureus. This inhibition increases with increasing concentration. The cytotoxicity and adhesion results showed that the PVA/SPG-AgNPs 1% sample had the best effect on fibroblast cells. The 1% sample was tested for the animal model, and after 14 days, it had a practical effect on the control. At 14 days post-treatment, a skinny epithelial layer was formed and covered the wound area, and these nanofibers were suitable for wound dressing. Consequently, PVA/SPG-AgNPs nanofibers could be a good option to cover burn wounds by speeding up the wound healing process and treatment costs.

Gallic Acid Enhances the Anti-Cancer Effect of Temozolomide in Human Glioma Cell Line via Inhibition of Akt and p38-MAPK Pathway

(1) Background: Temozolomide (TMZ), an oral alkylating agent, is used to treat malignant gliomas and other difficult-to-treat tumors. TMZ can enter the cerebrospinal fluid p.o. (per os) and does not need hepatic metabolism for activation of its use as a standard chemotherapeutic regimen after surgical resection of malignant glioma of the brain. However, the prognosis remains poor for most patients, and the survival rate is still unsatisfactory. Gallic acid (Ga) is a secondary metabolite existent in numerous plants. Ga shows various bioactivities, including antioxidant, anti-inflammatory, anticancer and antimicrobial effects. In this study, the latent enhanced anti-cancer efficacy of Ga in TMZ-treated U87MG cells (a human glioma line) was evaluated. (2) Methods: The U87MG cell line was cultured for 24 h. The cells were incubated with Ga alone, TMZ alone, or their combination for various time points. Cell viability and the drug combination index were evaluated by an XTT-based analysis and isobologram analysis, respectively. DNA destruction and intracellular reactive oxygen species (ROS) generation were analyzed by flow cytometer. The expression of various proteins was assessed via Western blotting. (3) Results: Compared with the action of TMZ alone or Ga alone, TMZ/Ga combination augmented the inhibition of cellular viability and apoptotic level in the U87MG glioma cell line. This enhanced anti-cancer effect correlated with the decreased expression of Bcl-2 and p-Akt, and corresponded with the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. In addition, Ga suppressed the TMZ-promoted ROS generation. (4) Conclusions: Ga can augment the anti-cancer effect of TMZ via the repression of Bcl-2 expression and Akt activation and the enhancement of the p38 MAPK pathway. Our results offer a novel probable approach for the medical treatment of malignant glioma.