Deoxyribonucleic Acid Damage Research Articles

Cold Atmospheric Plasma in Cancer Therapy: Molecular Insights, Novel Concepts, and Future Opportunities

Over the past 2 decades, cold atmospheric plasma (CAP) has been playing increasingly pivotal roles in cutting edge biomedical applications and has developed into an innovative field of research of growing importance. One promising new medical application of CAP is cancer treatment. Being able to richly induce both reactive oxygen and nitrogen species, CAP has been shown to effectively control events critical to cancer initiation/progression; selectively inducing Deoxyribonucleic acid (DNA) damage and apoptotic cell deaths, reducing tumor volume and vasculature, halting metastasis and conferring anti-tumor effects by taking advantage of e.g., synergies among and between chemotherapeutic drugs and nanoparticles. This paper discusses molecular and immunological mechanisms of CAP treatment as a potential tool against cancers, with a focus on the novel mechanisms by which CAP interacts with chemotherapeutic drugs and nanotechnology. We then attempt to draw parallels between what is already known about the mechanisms of CAP activity, some novel concepts and attempts of CAP synergy, and the knowledge we would need to develop CAP as a potential therapeutic strategy in oncotherapy. HIGHLIGHTS This article focused on critical review of cold atmospheric plasma’s (CAP) application in cancer therapy. CAP technology in cancer treatment has been expected to cause a medical and therapeutic implications. CAP has strong anticancer efficacy and has been reported about the cell migration and apoptosis. The major role of reactive oxygen and nitrogen species of plasma discharge is to control the core state of cancer transition. GRAPHICAL ABSTRACT

Significant role of secondary electrons in the formation of a multi-body chemical species spur produced by water radiolysis.

Scientific insights into water photolysis and radiolysis are essential for estimating the direct and indirect effects of deoxyribonucleic acid (DNA) damage. Secondary electrons from radiolysis intricately associated with both effects. In our previous paper, we simulated the femtosecond (1 × 10- 15s) dynamics of secondary electrons ejected by energy depositions of 11-19eV into water via high-energy electron transport using a time-dependent simulation code. The results contribute to the understanding of simple "intra-spur" chemical reactions of tree-body chemical species (hydrated electrons, hydronium ion and OH radical) in subsequent chemical processes. Herein, we simulate the dynamics of the electrons ejected by energy depositions of 20-30eV. The present results contribute to the understanding of complex "inter-spur" chemical reactions of the multi-body chemical species as well as for the formation of complex DNA damage with redox site and strand break on DNA. The simulation results present the earliest formation mechanism of an unclear multi-body chemical species spur when secondary electrons induce further ionisations or electronic excitations. The formation involves electron-water collisions, i.e. ionisation, electronic excitation, molecular excitation and elastic scattering. Our simulation results indicate that (1) most secondary electrons delocalise to ~ 12nm, and multiple collisions are sometimes induced in a water molecule at 22eV deposition energy. (2) The secondary electrons begin to induce diffuse band excitation of water around a few nm from the initial energy deposition site and delocalise to ~ 8nm at deposition energies ~ 25eV. (3) The secondary electron can cause one additional ionisation or electronic excitation at deposition energies > 30eV, forming a multi-body chemical species spur. Thus, we propose that the type and density of chemical species produced by water radiolysis strongly depend on the deposition energy. From our results, we discuss formation of complex DNA damage.

The Impact of Exercise on DNA Damage in Athletes: Causes, Mechanisms, and Case Studies

Although physical activity is important for the athlete’s health and performance, it may also lead to Deoxyribonucleic Acid (DNA) damage, which may have long-term health consequences and affect performance. This article summarizes different types of DNA damage that may occur in athletes, including their potential risk causes, such as mechanical stress, heat stress, and oxidative stress. Furthermore, several mechanisms by which physical activity might lead to DNA damage and affect health and performance are also discussed. Various strategies such as diet and nutrition, antioxidant supplements, cooling strategies, and recovery modalities are also presented to mitigate, prevent, and minimize the potential DNA damage upon physical activities. This article also highlights case studies of athletes who have experienced DNA damage and the effects on their performance and health. In summary, this article offers valuable perspectives on the intricate relationship between physical activity and DNA damage as well as the importance of addressing this issue in the context of athletic performance and health. Keywords: athlete, DNA damage, exercise, RONS

Effects of Pervari Honey from Türkiye on Proliferation, Oxidative Stress, and Apoptosis of Human Breast Cancer Cells

Breast cancer is one of the most common causes of deaths worldwide. Major obstacles to treatment have contributed to the increasing popularity of complementary or alternative therapies. Although recent results support the mechanism that honey induces cell death, the full mechanisms are still unknown. This study investigates the potential use of Pervari honey (PH) as an in vitro therapeutic agent in breast cancer. Firstly, the antioxidant capacity and total phenolic content of PH were tested. In addition, MCF-7 and MDA-MB-231 breast cancer cells treated with PH were examined for cell viability, reactive oxygen species production, oxidative deoxyribonucleic acid (DNA) damage, and apoptosis. Our results show that PH treatment decreased cell viability dose-dependently and increased reactive oxygen species (ROS) levels, oxidative DNA damage, and apoptosis rate. The present study suggests that honey is a promising source to produce pharmaceuticals and nutraceuticals for breast cancer therapy.

Enhanced skin benefits of EGCG loaded in nonapeptide-1-conjugated mesoporous silica nanoparticles to reverse skin photoaging

Epigallocatechin-3-gallate (EGCG), a catechin present in green tea, has been studied extensively for its potential as a cosmetic ingredient due to its various biological properties. However, the low stability and bioavailability of EGCG have hindered its effective utilization in cosmetic applications. This study, to improve the stability and bioavailability of EGCG for reversing skin photo-aging, nonapeptide-1-conjugated mesoporous silica nanoparticles (EGCG@NP-MSN) were fabricated to load EGCG. MSNs can regulate the EGCG release and provide ultraviolet light (UV) protection to possess excellent photostability. Nonapeptide-1 exhibits melanin transfer interference properties and reduces the melanin content in treated skin areas. In vitro and in vivo results confirmed that the EGCG-loaded MSNs retained antioxidant properties, effectively scavenged the melanin and significantly reduced the deoxyribonucleic acid (DNA) damage in skin cells exposed to UV irradiation. The melanin inhibition rate is 5.22 times and the tyrosinase inhibition rate is 1.57 times that of free EGCG. The utilization of this innovative platform offers the potential for enhanced stability, controlled release, and targeted action of EGCG, thereby providing significant advantages for skin application.This delivery system combines the advantages of antioxidant, anti-aging, and anti-UV radiation properties, paving the way for the cosmetics development with improved efficacy and better performance in promoting skin health and appearance.

Liquid water radiolysis induced by secondary electrons generated from MeV-energy carbon ions.

Fast ion beams induce damage to deoxyribonucleic acid (DNA) by chemical products, including secondary electrons, produced from interaction with liquid water in living cells. However, the production process of these chemical products in the Bragg peak region used in particle therapy is not fully understood. To investigate this process, we conducted experiments to evaluate the radiolytic yields produced when a liquid water jet in vacuum is irradiated with MeV-energy carbon beams. We used secondary ion mass spectrometry to measure the products, such as hydronium cations (H3O+) and hydroxyl anions (OH-), produced along with ·OH radicals, which are significant inducers of DNA damage formation. In addition, we simulated the ionization process in liquid water by incident ions and secondary electrons using a Monte Carlo code for radiation transport. Our results showed that secondary electrons, rather than incident ions, are the primary cause of ionization in water. We found that the production yield of H3O+ or OH- was linked to the frequency of ionization by secondary electrons in water, with these electrons having energies between 10.9 and 550eV. These electrons are responsible for ionizing the outer-shell electrons of water molecules. Finally, we present that the elementary processes contribute to advancing radiation biophysics and biochemistry, which study the formation mechanism of DNA damage.

A narrative review of mitochondrial dysfunction and male infertility.

Recent investigations have highlighted mitochondrial dysfunction as a major component in reduced sperm function and male infertility. The creation of energy, control of reactive oxygen species (ROS), apoptosis, and sperm motility are all critically dependent on mitochondria. The health of the male reproductive system may be significantly impacted by any alteration of mitochondrial structure, function, or integrity. This review intends to open the door to better diagnostic methods, novel therapy strategies, and improved reproductive outcomes for infertile couples by clarifying the crucial function of mitochondria. We searched PubMed, Google Scholar, and others for articles related to male infertility and mitochondrial dysfunction from 2014 to 2023. The articles related to the theme were preliminarily screened by abstract, and then the selected literature was read and summarized. In this essay, we examine the research on male infertility and mitochondrial malfunction. We investigate the intricate connection between sperm quality, deoxyribonucleic acid damage, oxidative stress (OS), and mitochondrial bioenergetics. We discuss about how spermatogenesis and sperm function are affected by mitochondrial mutations, deletions, and single nucleotide polymorphisms. We also explore the impact of age-related changes, lifestyle choices, and environmental factors on mitochondrial function and male fertility. This review also clarifies the mechanisms by which mitochondrial dysfunction impacts the viability, morphology, and capacitation of sperm, among other aspects of male reproductive health. Furthermore, we go over the recently developed field of mitochondrial treatments and possible therapeutic approaches that target mitochondrial malfunction to enhance male fertility. Mitochondria are important for sperm: The control of sperm motility, capacitation, and general quality is largely dependent on mitochondria. Deterioration of sperm motility and male infertility may result from disruption of the structure, function, or integrity of the mitochondria. Future studies should focus on figuring out the processes underlying mitochondrial dysfunction as fertility and reproductive health are significantly impacted by it. We discuss the evaluation of infertile men mitochondrial function defects and difficulties, and make recommendations for further study in this area. This article provides a thorough resource for clinicians, researchers, and reproductive biologists to understand the underlying mechanisms of male infertility and explore potential therapeutic interventions.

The Impact of Oleuropein on Cisplatin-Induced Toxicity in Cochlear Cells in Relation to the Expression of Deoxyribonucleic Acid Damage-Associated Genes.

Different organs respond differently to cisplatin (CDDP)-induced toxicity. Oleuropein (OLE) is a natural phenolic antioxidant. The purpose of this study was to determine the potential protective effect of OLE against CDDP-induced ototoxicity by evaluating expression of genes associated with deoxyribonucleic acid (DNA) damage and repair in cochlear cells. House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were treated using CDDP, OLE, and OLE-CDDP. The water-soluble tetrazolium salt assay was used for monitoring cell viability. Deoxyribonucleic acid damage in cells due to the CDDP, OLE, and combination treatments was determined using a flow-cytometric kit. The change in the expression of 84 genes associated with CCDP, OLE, and OLE-CDDP treatments that induced DNA damage was tested using the reverse transcription polymerase chain reaction array. Changes ≥3-fold were considered significant. House Ear Institute-Organ of Corti 1 cell viability was significantly reduced by CDDP. The OLE-CDDP combination restored the cell viability. Cisplatin increased the H2AX ratio, while OLE-CDDP combination decreased it. Some of the DNA damage-associated genes whose expression was upregulated with CDDP were downregulated with OLE-CDDP, while the expression of genes such as Gadd45g and Rev1 was further downregulated. The expression of DNA repair-related Abl1, Dbd2, Rad52, and Trp53 genes was downregulated with CDDP, whereas their expression was upregulated with OLE-CDDP treatment. In cochlear cells, the OLE-CDDP combination downregulated DNA damage-associated gene expression relative to that upregulated mainly by CDDP. The results revealed that OLE has a potential protective effect on CDDP-induced ototoxicity in cochlear cells by altering the expression of DNA damage-related genes.

Nuclear Chloride Ion-Selective Fluorescent Probe and Its Biological Applications.

Owing to the biological significance of Cl- in cells, several chemical fluorescent probes and biosensors have been constructed to monitor this anion in the cytosol and subcellular organelles. However, a fluorescent probe for the selective detection of nuclear Cl- has not been described thus far. In the current study, we developed the first nuclear Cl--selective biosensor, Cl-YFP-NLS, whose fluorescence was effectively quenched by this anion, and demonstrated that it is an efficient and powerful tool for determining the levels of nuclear Cl-. The results of cell studies using Cl-YFP-NLS as the probe suggested that the level of Cl- in the nucleus is lower than that in the cytosol. In addition, Cl-YFP-NLS along with lysosomal (Lyso-MQAE) and mitochondrial Cl--selective fluorescent probes (Mito-MQAE) were utilized to determine the effects of various substances on the levels of Cl- in subcellular organelles. The results showed that lysosomotropic agents decrease the lysosomal Cl- concentration and increase the levels of mitochondrial and nuclear Cl-. Also, observations suggested that substances capable of inducing mitochondrial outer membrane permeabilization without inducing lysosomal membrane permeabilization increase mitochondrial and nuclear Cl- concentrations but they do not affect the level of lysosomal Cl-. Moreover, a substance directly disrupting nuclear pore complexes increased the level of nuclear Cl- and did not change the levels of lysosomal and mitochondrial Cl-. Finally, nucleus-affecting substances that cause deoxyribonucleic acid damage and activate p53 and Bax increased the levels of mitochondrial and nuclear Cl- without influencing the level of lysosomal Cl-.

A pan-cancer interrogation of intronic polyadenylation and its association with cancer characteristics.

3'UTR-APAs have been extensively studied, but intronic polyadenylations (IPAs) remain largely unexplored. We characterized the profiles of 22260 IPAs in 9679 patient samples across 32 cancer types from the Cancer Genome Atlas cohort. By comparing tumor and paired normal tissues, we identified 180 ~ 4645 dysregulated IPAs in 132 ~ 2249 genes in each of 690 patient tumors from 22 cancer types that showed consistent patterns within individual cancer types. We selected 2741 genes that showed consistently patterns across cancer types, including 1834 pan-cancer tumor-enriched and 907 tumor-depleted IPA genes; the former were amply represented in the functional pathways such as deoxyribonucleic acid damage repair. Expression of IPA isoforms was associated with tumor mutation burden and patient characteristics (e.g. sex, race, cancer stages, and subtypes) in cancer-specific and feature-specific manners, and could be a more accurate prognostic marker than gene expression (summary of all isoforms). In summary, our study reveals the roles and the clinical relevance of tumor-associated IPAs.

Gallium complex K6 inhibits colorectal cancer by increasing ROS levels to induce DNA damage and enhance phosphatase and tensin homolog activity.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. In the clinical realm, platinum-based drugs hold an important role in the chemotherapy of CRC. Nonetheless, a multitude of patients, due to tumor protein 53 (TP53) gene mutations, experience the emergence of drug resistance. This phenomenon gravely impairs the effectiveness of therapy and long-term prognosis. Gallium, a metallic element akin to iron, has been reported that has the potential to be used to develop new metal anticancer drugs. In this study, we screened and established the gallium complex K6 as a potent antitumor agent in both in vitro and in vivo. K6 exhibited superior efficacy in impeding the growth, proliferation, and viability of CRC cells carrying TP53 mutations compared to oxaliplatin. Mechanistically, K6 escalated reactive oxygen species levels and led deoxyribonucleic acid (DNA) damage. Furthermore, K6 effectively suppressed the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB)/glycogen synthase kinase 3 beta (GSK3β) pathway, leading to the degradation of its downstream effectors myelocytomatosis (c-Myc) and Krueppel-like factor 5 (KLF5). Conversely, K6 diminished the protein expression of WW domain-containing protein 1 (WWP1) while activating phosphatase and tensin homolog (PTEN) through c-Myc degradation. This dual action further demonstrated the potential of K6 as a promising therapeutic compound for TP53-mutated CRC.

Specificity of DNA damage formation induced by femtosecond near-infrared laser filamentation in water

We investigated the deoxyribonucleic acid (DNA) damage induced by laser filamentation, which was generated by focusing femtosecond near-infrared Ti:Sapphire laser light in water at several repetition rates ranging from 1000 Hz to 10 Hz. Using plasmid DNA (pUC19), the single-strand break, double-strand break, nucleobase lesions, and the fragmented DNA were analyzed and quantified by agarose gel electrophoresis. Additionally, the H2O2 concentration after irradiation was determined. We observed that (1) the DNA damage per laser shot and (2) the enzyme-sensitive base lesions per total DNA damage decreased as the laser repetition rate increased. Furthermore, (3) extraordinarily short DNA fragments were likely to be produced, compared with those produced using X-rays, and (4) most OH radicals could be eliminated by recombination to generate H2O2, preventing them from damaging the DNA. The Monte-Carlo simulation of the strand break formation implies that the observed dependency of strand break efficiency on the laser repetition rate is mainly due to diffusion of DNA molecules. These findings quantitatively and qualitatively revealed that an intense laser pulse induces a specific DNA damage profile that is not induced by X-rays, a sparsely ionizing radiation source.

Oxidative Stress, DNA Damage, Inflammation and Endothelial Dysfunction in Snakebite-Induced Acute Kidney Injury

Background Snakebite-induced acute kidney injury (SAKI) is a life-threatening complication. Despite its impact on public health, the understanding of the underlying cellular and molecular mechanisms remains limited. There is a lack of studies investigating the role of oxidative stress, oxidative deoxyribonucleic acid (DNA) damage, inflammation, and endothelial dysfunction in SAKI. This study aims to address this knowledge gap. Materials and Methods Biomarkers of oxidative stress, including oxidative DNA damage, inflammation, and endothelial dysfunction were assessed in 30 patients with SAKI and 30 healthy controls. Malondialdehyde (MDA), protein carbonyl content (PCC), advanced glycation end products (AGEs), 8-hydroxy-2’-deoxyguanosine (8-OHdG), ferric reducing ability of plasma (FRAP), high-sensitivity C-reactive protein (hs-CRP), and nitric oxide (NO) were used as biomarkers. Results We found significantly elevated levels of MDA (2.1590±0.68221 µmol/L vs 0.8769±0.2958 µmol/L, p = <0.001), PCC (0.0905±0.040 nmol/L vs 0.0501±0.024 nmol/L, p = <0.001) and 8-OHdG (47.0757±37.09105 ng/mL vs 18.8450±9.31479 ng/mL, p = <0.001) in SAKI patients compared to controls, indicating increased oxidative damage to lipids, proteins, and DNA respectively. Although AGEs showed higher levels in SAKI patients, the difference was not significant. FRAP levels were significantly reduced [0.214 (0.051-0.489) mmol/L vs 0.470 (0.136-0.564) mmol/L, p = 0.024], indicating compromised antioxidant capacity. Significantly elevated levels of hs-CRP [40.18 (16.96-77.56) mg/L vs 1.44 (0.5-4.45) mg/L, p = <0.001] and NO [25.59 (22.75-28.43) µmol/L vs 14.218 (11.37-16.35) µmol/L, p = <0.001] confirmed the presence of inflammation and endothelial dysfunction in these patients. Conclusion Our study demonstrated oxidative stress, including oxidative DNA damage, inflammation, and endothelial dysfunction, in SAKI patients. Understanding these intricate mechanisms could lead to the development of novel diagnostic tools and therapeutic strategies.

Structure, Functions And Clinical Significance Of DNA: A Review Article

The deoxyribonucleic acid (DNA) carries hereditary codes which is translated by the cells to synthesize the ribonucleic acid (RNA) and polypeptides which can generate and perform vital function. The double helix structure is the most studied model of the DNA that was proposed by Watson and Crick. The capability of DNA to work as a genetic material can be stored and conducted during cell division to permit this information to be doubled and transmitted to the incoming generation. Any damage in the structure of DNA is an essential direct cause for the progression of cancer and other disorders. The factors for DNA damage can be classified as exogenous and endogenous factors. In this review article, we highlight the evidence-supported information about the structure, functions and clinical significance of DNA.

Assessment of Carcinogenic/Mutagenic Potential of Different Series of Synthetic Compounds

The new drug research is usually based on synthesis medicine. The use of these medications has created problems such as tolerance in humans, for a long time and due to legitimate use of anti-infection, microbial defense against branded medication is growing. A mutagensis study by Ames in the early 1970's, used worldwide by drug and chemicals companies to diagnose mutagens carcinogenes, making it possible for them to be detected, and to be added to the mutagenic synthesis portion or radiation source triggering irreversible changes, and to the genetic material transmitted from the parent. deoxyribonucleic acid (DNA). The purpose of this study was to assessment of carcinogenicity of synthetic compounds series by hemolytic, Ames and Damaged DNA protection assay. The cytotoxicity was determined with hemolytic assay and DNA Damage protection assay while mutagenicity was resolute by using S. typhimurium TA100 and TA98 strains. It is concluded that the compounds with less hemolytic compounds are good for uses in drugs. Synthetic compounds were determined to be non- mutagenic in nature. Analysis of variance (ANOVA) was applied to compare the hemolysis percent between different concentrations.

Gastrointestinal Polyps and Polyposis in Individuals Harboring Germline CHEK2 Mutations.

Checkpoint kinase 2 is a tumor suppressor gene in the deoxyribonucleic acid damage checkpoint system that may be mutated in several cancers. Patients with germline checkpoint kinase 2 mutations and multiple colon polyps were noted during routine care, and genetic testing is recommended for patients with as few as 10 lifetime polyps. This study assessed whether checkpoint kinase 2 is associated with attenuated or oligopolyposis and characterized the gastrointestinal clinicopathologic profile. Retrospective observational study. Records from patients harboring germline checkpoint kinase 2 mutations from 1999-2020 were reviewed. A total of 45 patients with germline checkpoint kinase 2 mutations with endoscopic examinations. Description of clinicopathologic variables. Twenty-five of 45 patients had polyps: 3 with only upper gastrointestinal polyps, 17 with only lower gastrointestinal polyps and 5 with both upper and lower gastrointestinal polyps. The most common germline checkpoint kinase 2 mutations in patients with polyps were p.S428F (n = 10), p.I157T (n = 4) and p.T476M (n = 2), with other mutations present in 1 patient each. Among patients with lower gastrointestinal polyps, 9 had adenomas, 6 had serrated polyps, 1 had an inflammatory polyp and 6 had both adenomatous and serrated polyps. Three patients (p.I157T, n = 2; p.R117G, n = 1) had >10 adenomas, and 1 (p.G259fs) had 18 serrated polyps. Five patients (11.1%) developed colorectal adenocarcinoma, including 2 with >10 adenomas. Five patients with p.S428F (50%) exclusively had right- sided adenomas. Single-center descriptive study. Germline checkpoint kinase 2 mutations should be considered in patients with polyposis. The preponderance of right- sided adenomas in patients with p.S428F mutations suggests the importance of right-sided colonoscopy in these patients. See Video Abstract.

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.

A REVIEW ON THE CHEMICAL-INDUCED EXPERIMENTAL MODEL OF CARDIOTOXICITY

Drug-induced cardiotoxicity is a major concern during drug development, prompting the need for reliable experimental models to thoroughly assess potential cardioprotective drugs. The review delves into the intricacies of various models for drug-induced cardiotoxicity in experimental animals, with a specific focus on streptozotocin, isoprenaline, and antineoplastic drugs like cisplatin, doxorubicin, and 5-fluorouracil in rats and mice. Streptozotocin-induced cardiotoxicity is characterized by oxidative stress, inflammation, and mitochondrial dysfunction, resulting in myocardial damage and impaired cardiac function. Preclinical studies employing streptozotocin-induced cardiotoxicity models have revealed crucial pathways related to diabetic cardiomyopathy, aiding the evaluation of potential cardioprotective interventions. Isoprenaline, a beta-adrenergic agonist, is known for inducing acute myocardial injury resembling cardiac ischemia and heart failure in animals. Its mechanism involves overstimulation of beta-adrenergic receptors, calcium overload, oxidative stress, and apoptosis. Isoprenaline-induced models have offered insights into acute myocardial injury pathophysiology and facilitated the screening of cardioprotective agents against Myocardial Infarction (MI) and injury. Antineoplastic drugs, such as cisplatin, doxorubicin, and 5-fluorouracil, are linked to significant cardiotoxic effects, including cardiomyopathy and heart failure. Animal models have revealed dose-dependent cardiomyopathy, shedding light on underlying mechanisms like oxidative stress, Deoxyribonucleic Acid (DNA) damage, and mitochondrial dysfunction. The article aims to consolidate the current understanding of the pathophysiology and mechanisms behind drug-induced cardiac damage. Additionally, it underscores the importance of using animal models in preclinical evaluations to assess drug safety and efficacy and to develop potential cardioprotective therapies.

Monte Carlo-Based Nanoscale Dosimetry Holds Promise for Radiopharmaceutical Therapy Involving Auger Electron Emitters.

Radiopharmaceutical therapy (RPT) is evolving as a promising strategy for treating cancer. As interest grows in short-range particles, like Auger electrons, understanding the dose-response relationship at the deoxyribonucleic acid (DNA) level has become essential. In this study, we used the Geant4-DNA toolkit to evaluate DNA damage caused by the Auger-electron-emitting isotope I-125. We compared the energy deposition and single strand break (SSB) yield at each base pair location in a short B-form DNA (B-DNA) geometry with existing simulation and experimental data, considering both physical direct and chemical indirect hits. Additionally, we evaluated dosimetric differences between our high-resolution B-DNA target and a previously published simple B-DNA geometry. Overall, our benchmarking results for SSB yield from I-125 decay exhibited good agreement with both simulation and experimental data. Using this simulation, we then evaluated the SSB and double strand break (DSB) yields caused by a theranostic Br-77-labeled poly ADP ribose polymerase (PARP) inhibitor radiopharmaceutical. The results indicated a predominant contribution of chemical indirect hits over physical direct hits in generating SSB and DSB. This study lays the foundation for future investigations into the nano-dosimetric properties of RPT.

Evaluasi Kerusakan DNA Spermatozoa Semen Cair Babi Menggunakan Pewarnaan Toluidine Blue

The integrity of the deoxyribonucleic acid (DNA) in sperm plays a crucial role in the fertilization process and embryonic development. This study aimed to evaluate the level of the DNA fragmentation of boar sperm in tris-citrate-fructose extender preserved at temperatures between 16-18°C for 3 days. The level of sperm DNA damage was analysed using toluidine blue (TB) staining. Pig semen collected from 4 male pigs aged 1.3-1.8 years was used as the research sample. Semen collected was conducted twice a week. The experimental method using a Completely Randomized Design with 4 storage duration groups as follows: Group I (0 hours of storage), Group II (24 hours of storage), Group III (48 hours of storage), and Group IV (72 hours of storage), each with 5 replications. The data were analysed using analysis of variance (ANOVA) and, if significant differences were found, Duncan's test was performed. The results of the evaluation of the percentage of DNA damage during the storage process at 16-180C at 0 hours, 24 hours, 48 hours and 72 hours was: 0.33 ± 1.66%, 0.80 ± 0.447%, 1.60 ± 1.14% and 2.80 ± 0.447%, respectively. These results demonstrate that liquid boar semen preserved with tris citrate fructose extender at 16-18 °C for 3 days has spermatozoa DNA damage levels within the normal range, making it suitable for artificial insemination and ensuring optimal AI success.