Prevent DNA Damage Research Articles

α-Terpineol Induces Shelterin Components TRF1 and TRF2 to Mitigate Senescence and Telomere Integrity Loss via A Telomerase-Independent Pathway.

Cellular senescence is a hallmark of aging characterized by irreversible growth arrest and functional decline. Progressive telomeric DNA shortening in dividing somatic cells, programmed during development, leads to critically short telomeres that trigger replicative senescence and thereby contribute to aging. Therefore, protecting telomeres from DNA damage is essential in order to avoid entry into senescence and organismal aging. In several organisms, including mammals, telomeres are protected by a protein complex named shelterin that prevents DNA damage at the chromosome ends through the specific function of its subunits. Here, we reveal that the nuclear protein levels of shelterin components TRF1 and TRF2 decline in fibroblasts reaching senescence. Notably, we identify α-terpineol as an activator that effectively enhances TRF1 and TRF2 levels in a telomerase-independent manner, counteracting the senescence-associated decline in these crucial proteins. Moreover, α-terpineol ameliorates the cells' response to oxidative DNA damage, particularly at the telomeric regions, thus preserving telomere length and delaying senescence. More importantly, our findings reveal the significance of the PI3K/AKT pathway in the regulation of shelterin components responsible for preserving telomere integrity. In conclusion, this study deepens our understanding of the molecular pathways involved in senescence-associated telomere dysfunction and highlights the potential of shelterin components to serve as targets of therapeutic interventions, aimed at promoting healthy aging and combating age-related diseases.

Nucleic acid binding affinity and antioxidant activity of N-m-Tolyl-4-Chlorophenoxyacetohydroxamicacid.

Hydroxamic acids represent a group of weak organic acids, both naturally occurring and synthetically derived, characterized by the general formula RC(= O)N(R'OH). In this study, we investigated the binding behavior of N-m-tolyl-4-chlorophenoxyaceto hydroxamic acid with calf thymus DNA (ct-DNA) and torula yeast RNA (t-RNA) through a combination of techniques including UV-visible spectroscopy, fluorescence emission analysis, viscometry, and computational simulations using AutoDock4 software. Our findings reveal that the mode of binding between the compound and the nucleic acids is consistent with intercalation. Competitive binding experiments demonstrated that the complex competes effectively with ethidium bromide (EB) for binding to ct-DNA/t-RNA, displacing EB from its binding sites. Additionally, the introduction of the compound into the DNA-EB system resulted in a quenching of fluorescence emission peaks. Analysis of absorption spectra indicated a red shift and hypochromic shift when the compound interacted with DNA, further supporting the intercalative binding mode. The calculated binding constant (Kb) value for the compound is 6.62 × 104M-1 and 5.40 × 103M-1 indicating a strong interaction with ct-DNA and t-RNA respectively. We determined the Stern-Volmer constants for ct-DNA and t-RNA as 9.96 × 104M-1 and 8.13 × 105M-1, respectively. The binding free energy values for ct-DNA/t-RNA were calculated to be -3.741 × 107 and -5.425 × 108kcal/mol, respectively. Viscometric studies corroborated the UV results, showing a continuous increase in relative viscosity of ct-DNA/t-RNA solutions with the addition of the optimal hydroxamic acid concentration. Furthermore, we assessed the antioxidant activity of the compound using DPPH-radical scavenging and β-carotene linoleic acid assays. Gel electrophoresis results demonstrated the compound's remarkable efficacy in preventing DNA damage. Collectively, all experimental evidence supports the conclusion that N-m-tolyl-4-chlorophenoxyaceto hydroxamic acid binds to ct-DNA/t-RNA through an intercalative mechanism, which is consistent with our molecular docking simulations.

Sea conch (Rapana venosa) peptide hydrolysate regulates NF‐κB pathway and restores intestinal immune homeostasis in DSS‐induced colitis mice

AbstractInflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract. Sea conch peptide hydrolysate (CPH) was produced by enzymatic digestion of fresh conch meat with trypsin enzyme. To analyze the molecular composition, functional groups, and structural morphology of the hydrolysate, we employed liquid chromatography–mass spectrometry (LC–MS), Fourier‐transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Results confirmed that crude protein could be effectively digested by enzymes to generate peptides. In this study, we evaluated the bioactivities of CPH on dextran sulfate solution (DSS)‐induced colitis in mice. The findings demonstrated that CPH supplementation improved body weight, food and water intake, and colon length. The therapeutic efficacy and immunoregulatory effect of CPH were further determined. Our results exhibited that CPH treatment significantly ameliorated pathological symptoms by enhancing intestinal integrity, mucin production, and goblet cell count. Moreover, the immunoregulatory effect of CPH on mRNA expression levels of different pro‐ and anti‐inflammatory cytokines was determined. Results exhibited a decrease in the expression of pro‐inflammatory cytokines and an increase in anti‐inflammatory cytokines in the colon. Additionally, the CPH administration modulates the nuclear factor kappa B (NF‐κB) pathway, preventing DNA damage and cell death. Assays for apoptosis and DNA damage revealed that CPH reduced oxidative DNA damage and apoptosis. These findings highlight the immunomodulatory and treatment amelioration effect of CPH in reducing the severity of colitis.

TP53 Gene Polymorphism (Rs1042522) in Rheumatoid Arthritis and Systemic Lupus Erythematosus: An Updated Systematic Review and Meta-Analysis.

The p53 protein has important roles in apoptosis, proliferation, and prevention of DNA damage. Several studies have reported that TP53 gene polymorphism is associated with various autoimmune diseases, including Rheumatoid arthritis (RA) and Systemic lupus erythematosus (SLE). Evaluation of the correlation between TP53 gene rs1042522 polymorphism and RA and SLE risk by meta-analysis. Databases, including PubMed and Scopus, were searched to find studies assessing the association between TP53 gene polymorphism and RA and SLE risk in different populations up to August 2022. The protocol of this article was registered on the International Prospective Register Of Systematic Reviews (PROSPERO number: CRD42022309655). Herein, 7 case-control studies, including 2498 cases and 3799 controls in the SLE group, and 6 case-control studies comprising 1593 cases and 4460 controls in the RA group that investigated rs1042522 SNP were included in the meta-analysis. Herein, CG genotypes were more frequent in healthy participants compared to SLE patients and may associated with a decreased SLE risk (OR=0.85, CI: 0.76-0.95, P-value <0.006). Besides, dominant and recessive models of CC+ CG vs. GG were also protective for SLE risk (OR=0.85, CI: 0.76-0.95, P-value <0.004). In summary, this study discloses a weak correlation between rs1042522 and a decreased risk of SLE. However, no significant association was found in RA.

Chemoproteomic profiling unveils binding and functional diversity of endogenous proteins that interact with endogenous triplex DNA.

Triplex DNA structures, formed when a third DNA strand wraps around the major groove of DNA, are key molecular regulators and genomic threats. However, the regulatory network governing triplex DNA dynamics remains poorly understood. Here we reveal the binding and functional repertoire of proteins that interact with triplex DNA through chemoproteomic profiling in living cells. We develop a chemical probe that exhibits exceptional specificity towards triplex DNA. By employing a co-binding-mediated proximity capture strategy, we enrich triplex DNA interactome for quantitative proteomics analysis. This enables the identification of a comprehensive list of proteins that interact with triplex DNA, characterized by diverse binding properties and regulatory mechanisms in their native chromatin context. As a demonstration, we validate DDX3X as an ATP-independent triplex DNA helicase to unwind substrates with a 5' overhang to prevent DNA damage. Overall, our study provides a valuable resource for exploring the biology and translational potential of triplex DNA.

Effects of alfa lipoic acid and coenzyme Q10 treatment on AFB1-induced oxidative, inflammatory, and DNA damages in rats

Food contamination with Aflatoxin B1 (AFB1) is a worldwide concern that adversely affects animal and human health. The study aimed to evaluate the protective effect of alpha lipoic acid (ALA) and/or co-enzyme Q10 (CQ10) against the harmful effects of AFB1 on the liver and kidneys. Fifty-six mature male Wistar Albino rats (180–200 g) were divided into seven groups, each with eight rats: (1) saline was given as a control, (2) ALA (100 mg/kg bw/day) was given by stomach gavage for fifteen days, and (3) CQ10 (10 mg/kg bw/day) was given by stomach gavage for fifteen days. Group (4) orally given AFB1 (2.5 mg/kg bw) on days 12th and 14th, (5) received AFB1 and ALA, (6) received AFB1 and CQ10, and (7) received AFB1, ALA, and CQ10, as previously described in the ALA, CQ10, and AFB1 groups. After the exposure to AFB1, a significant increase in liver markers (AST, ALT, ALP, and LDH) and renal function tests (BUN and creatinine) was observed compared with the control. ALA and/or CQ10 significantly reduced enzymes of liver and renal functions, as compared with AFB1. AFB1 exposure threw off the balance between oxidants and antioxidants. Still, ALA and/or CQ10 made oxidative stress (MDA, NO, and 8-OHdG) much lower and antioxidant activities (GSH, GSH-Px, SOD, and CAT) much higher. When we used the two together, the activities matched the control levels. Interestingly, this study shows that ALA and CQ10 significantly lowered IL-1β, IL-6, and TNF-α levels compared to the control values when used together after AFB1 exposure caused robust inflammation. Some CQ10 treatment parameters significantly outperformed those of ALA. ALA and CQ10 together worked better than either one alone to protect against AFB1-induced toxicity in the hepatic and renal parenchyma in terms of reducing inflammation, preventing DNA damage, and fighting free radicals.

A manganese-doped layered double hydroxide loaded with lactate oxidase and DNA repair inhibitors for synergistically enhanced tumor immunotherapy

Tumor immunotherapy has gained more and more attention in tumor treatment. However, the accumulation of lactic acid in tumor tissue inhibits the response of immune cells to form an immunosuppressive microenvironment (ISME). To reverse the ISME, an acid-responsive nanoplatform (termed as MLLN@HA) is reported for synergistically enhanced tumor immunotherapy. MLLN@HA is constructed by the co-loading of lactate oxidase (LOX) and DNA repair inhibitor (NU7441) in a manganese-doped layered double hydroxide (Mn-LDH), and then modified with hyaluronic acid (HA) for tumor-targeted delivery. After endocytosis by tumor cells, MLLN@HA decomposes and releases LOX, NU7441 and Mn2+ ions in the acidic tumor microenvironment. The released LOX catalyzes the conversion of lactic acid into hydrogen peroxide (H2O2), which not only alleviates the ISME, but also provides reactants for the Mn2+-mediated Fenton-like reaction to enhance chemodynamic therapy (CDT). Released NU7441 prevents CDT-induced DNA damage from being repaired, thereby increasing double-stranded DNA (dsDNA) fragments within tumor cells. Importantly, the released Mn2+ ions enhance the sensitivity of cyclic GMP-AMP synthase (cGAS) to dsDNA fragments, and activate the stimulator of interferon genes (STING) to induce an anti-tumor immune response. Such an orchestrated immune-boosting strategy ultimately achieves effective tumor growth inhibition and prevents tumor lung metastasis. Statement of significanceTo improve the efficacy of tumor immunotherapy, an innovative acid-responsive MLLN@HA nanoplatform was developed for synergistically enhanced tumor immunotherapy. The MLLN@HA actively targets to tumor cells through the interaction of HA with CD44, and then degrades to release LOX, NU7441 and Mn2+ ions in the acidic tumor microenvironment. The released LOX generates H2O2 for the Mn2+-mediated Fenton reaction and reverses the ISME by consuming lactate. NU7441 prevents DNA damage repair, leading to an increased concentration of free DNA fragments, while Mn2+ ions activate the cGAS-STING pathway, enhancing the systemic anti-tumor immune response. The orchestrated immune-boosting nanoplatform effectively inhibits tumor growth and lung metastasis, presenting a promising strategy for cancer treatment.

Increased DNA damage of adipose tissue-derived mesenchymal stem cells under inflammatory conditions

Cells have evolved various DNA repair mechanisms to prevent DNA damage from building up. Malfunctions during DNA repair can influence cellular homeostasis because they can bring on genomic instability through the improper recognition of DNA damage or dysregulation of the repair process. Maintaining proper DNA repair is also essential for stem cells (SCs), as they provide a differentiated cell population to the living organism. SCs are regularly used in personalized stem cell therapy. Patients must be treated with specific activators to produce these SCs effectively. This report investigated the impact of treating mesenchymal stem cells (MSC) with lipopolysaccharide, tumor necrosis factor, interferon-gamma, polyinosinic acid, interleukin 1 beta, while monitoring their transcription-related response using next-generation sequencing. RNA sequencing revealed robust gene expression changes, including those of specific genes encoding proteins implicated in DNA damage response. Stem cells can effectively repair specific DNA damages; moreover, they fail to undergo senescence or cell death when genetic lesions accumulate. Here, we draw attention to an elevated DNA repair activation following MSC induction, which may be the main reason for the ineffective stem cell transplantation and may also contribute to the genetic drift that can initiate tumor formation.

HLTF resolves G4s and promotes G4-induced replication fork slowing to maintain genome stability

G-quadruplexes (G4s) form throughout the genome and influence important cellular processes. Their deregulation can challenge DNA replication fork progression and threaten genome stability. Here, we demonstrate an unexpected role for the double-stranded DNA (dsDNA) translocase helicase-like transcription factor (HLTF) in responding to G4s. We show that HLTF, which is enriched at G4s in the human genome, can directly unfold G4s invitro and uses this ATP-dependent translocase function to suppress G4 accumulation throughout the cell cycle. Additionally, MSH2 (a component of MutS heterodimers that bind G4s) and HLTF act synergistically to suppress G4 accumulation, restrict alternative lengthening of telomeres, and promote resistance to G4-stabilizing drugs. In a discrete but complementary role, HLTF restrains DNA synthesis when G4s are stabilized by suppressing primase-polymerase (PrimPol)-dependent repriming. Together, the distinct roles of HLTF in the G4 response prevent DNA damage and potentially mutagenic replication to safeguard genome stability.

DNA fork remodeling proteins, Zranb3 and Smarcal1, are uniquely essential for aging hematopoiesis.

Over a lifetime, hematopoietic stem and progenitor cells (HSPCs) are forced to repeatedly proliferate to maintain hematopoiesis, increasing their susceptibility to DNA damaging replication stress. However, the proteins that mitigate this stress, protect HSPC replication, and prevent aging-driven dysregulation are unknown. We report two evolutionarily conserved, ubiquitously expressed chromatin remodeling enzymes with similar DNA replication fork reversal biochemical functions, Zranb3 and Smarcal1, have surprisingly specialized roles in distinct HSPC populations. While both proteins actively mitigate replication stress and prevent DNA damage and breaks during lifelong hematopoiesis, the loss of either resulted in distinct biochemical and biological consequences. Notably, defective long-term HSC function, revealed with bone marrow transplantation, caused hematopoiesis abnormalities in young mice lacking Zranb3. Aging significantly worsened these hematopoiesis defects in Zranb3-deficient mice, including accelerating the onset of myeloid-biased hematopoietic dysregulation to early in life. Such Zranb3-deficient HSPC abnormalities with age were driven by accumulated DNA damage and replication stress. Conversely, Smarcal1 loss primarily negatively affected progenitor cell functions that were exacerbated with aging, resulting in a lymphoid bias. Simultaneous loss of both Zranb3 and Smarcal1 compounded HSPC defects. Additionally, HSPC DNA replication fork dynamics had unanticipated HSPC type and age plasticity that depended on the stress and Zranb3 and/or Smarcal1. Our data reveal both Zranb3 and Smarcal1 have essential HSPC cell intrinsic functions in lifelong hematopoiesis that protect HSPCs from replication stress and DNA damage in unexpected, unique ways.

Role of senataxin in R-loop-mediated neurodegeneration.

Senataxin is an RNA:DNA helicase that plays an important role in the resolution of RNA:DNA hybrids (R-loops) formed during transcription. R-loops are involved in the regulation of biological processes such as immunoglobulin class switching, gene expression and DNA repair. Excessive accumulation of R-loops results in DNA damage and loss of genomic integrity. Senataxin is critical for maintaining optimal levels of R-loops to prevent DNA damage and acts as a genome guardian. Within the nucleus, senataxin interacts with various RNA processing factors and DNA damage response and repair proteins. Senataxin interactors include survival motor neuron and zinc finger protein 1, with whom it co-localizes in sub-nuclear bodies. Despite its ubiquitous expression, mutations in senataxin specifically affect neurons and result in distinct neurodegenerative diseases such as amyotrophic lateral sclerosis type 4 and ataxia with oculomotor apraxia type 2, which are attributed to the gain-of-function and the loss-of-function mutations in senataxin, respectively. In addition, low levels of senataxin (loss-of-function) in spinal muscular atrophy result in the accumulation of R-loops causing DNA damage and motor neuron degeneration. Senataxin may play multiple functions in diverse cellular processes; however, its emerging role in R-loop resolution and maintenance of genomic integrity is gaining attention in the field of neurodegenerative diseases. In this review, we highlight the role of senataxin in R-loop resolution and its potential as a therapeutic target to treat neurodegenerative diseases.

Ionizing Radiation-Induced Oxidative Stress in Computed Tomography-Effect of Vitamin C on Prevention of DNA Damage: PREVIR-C Randomized Controlled Trial Study Protocol.

Exposure to ionizing radiation (IR) is inevitable in various X-ray imaging examinations, with computed tomography (CT) being a major contributor to increased human radiation exposure. Ionizing radiation may cause structural damage to macromolecules, particularly DNA, mostly through an indirect pathway in diagnostic imaging. The indirect pathway primarily involves the generation of reactive oxygen species (ROS) due to water radiolysis induced by IR, leading to DNA damage, including double-strand breaks (DSB), which are highly cytotoxic. Antioxidants, substances that prevent oxidative damage, are proposed as potential radioprotective agents. This Study Protocol article presents the rationale for selecting vitamin C as a preventive measure against CT-associated IR-induced DNA damage, to be investigated in a randomized placebo-controlled trial, with a full in vivo design, using an oral easy-to-use schedule administration in the outpatient setting, for the single CT examination with the highest total global IR dose burden (contrast-enhanced abdomen and pelvis CT). The study also aims to explore the mediating role of oxidative stress, and it has been written in adherence to the Standard Protocol Items recommendations.

Role of Vitamin C in Skin Aging Mechanism-A Narrative Review

Background: The cosmetics industry has seen significant growth due to the pursuit of beauty and the increasing demand for anti-aging agents. These agents, derived from active ingredients like polyphenols, retinol, and pro-xylane, are categorized into synthetic, plant, and fermentation components. Among these, synthetic components such as vitamins A, B, and C are widely used. Vitamin C has long been utilized in food and medicine for its beneficial effects, including its crucial role in collagen formation. The aging process, while slow and prolonged, is significantly influenced by vitamin C, making it an indispensable component for skin health. Objective: This study aimed to determine how vitamin C helps reduce aging and controls the mechanisms associated with skin aging. Methods: A comprehensive narrative review was conducted by synthesizing existing literature from electronic databases such as PubMed, Scopus, and Google Scholar. The search included keywords like "Vitamin C," "skin aging," "collagen synthesis," "oxidative stress," and "melanogenesis." Studies included were peer-reviewed, written in English, and published within the last 20 years. Both in vivo and in vitro studies were considered to assess the biochemical functions of vitamin C, its protective roles against UV radiation, and its therapeutic potential in various skin conditions. Data were critically analyzed, focusing on study designs, sample sizes, and statistical analyses. Results: Vitamin C was found to enhance collagen synthesis, with studies showing a significant increase in collagen production (Makrantonaki &amp; Zouboulis, 2007). Its antioxidant properties effectively neutralized reactive oxygen species, reducing oxidative stress and preventing DNA damage, with a reduction of ROS levels by 30-50% in UV-exposed skin cells (Rinnerthaler et al., 2015). Inhibitory effects on melanogenesis were observed, with vitamin C reducing melanin synthesis by 25% (Shimada et al., 2009). Additionally, therapeutic benefits were noted in treating acne, psoriasis, and hyperpigmentation, with a 40% improvement in acne scars (Chawla, 2014) and a 35% reduction in psoriasis symptoms (Soodgupta et al., 2014). Conclusion: Vitamin C plays a crucial role in maintaining skin health and combating aging through various mechanisms, including enhancing collagen synthesis, providing antioxidant protection, inhibiting melanogenesis, and treating skin diseases. Its consistent findings across multiple studies support its continued use in clinical and cosmetic dermatology. Further research with standardized methodologies is recommended to optimize its application and fully understand its potential.

PHF2-mediated H3K9me balance orchestrates heterochromatin stability and neural progenitor proliferation

Heterochromatin stability is crucial for progenitor proliferation during early neurogenesis. It relays on the maintenance of local hubs of H3K9me. However, understanding the formation of efficient localized levels of H3K9me remains limited. To address this question, we used neural stem cells to analyze the function of the H3K9me2 demethylase PHF2, which is crucial for progenitor proliferation. Through mass-spectroscopy and genome-wide assays, we show that PHF2 interacts with heterochromatin components and is enriched at pericentromeric heterochromatin (PcH) boundaries where it maintains transcriptional activity. This binding is essential for silencing the satellite repeats, preventing DNA damage and genome instability. PHF2’s depletion increases the transcription of heterochromatic repeats, accompanied by a decrease in H3K9me3 levels and alterations in PcH organization. We further show that PHF2’s PHD and catalytic domains are crucial for maintaining PcH stability, thereby safeguarding genome integrity. These results highlight the multifaceted nature of PHF2’s functions in maintaining heterochromatin stability and regulating gene expression during neural development. Our study unravels the intricate relationship between heterochromatin stability and progenitor proliferation during mammalian neurogenesis.

Low magnesium in conjunction with high homocysteine increases DNA damage in healthy middle aged Australians

PurposeMagnesium is one of the most common elements in the human body and plays an important role as a cofactor of enzymes required for DNA replication and repair and many other biochemical mechanisms including sensing and regulating one-carbon metabolism deficiencies. Low intake of magnesium can increase the risk of many diseases, in particular, chronic degenerative disorders. However, its role in prevention of DNA damage has not been studied fully in humans so far. Therefore, we tested the hypothesis that magnesium deficiency either on its own or in conjunction with high homocysteine (Hcy) induces DNA damage in vivo in humans.MethodsThe present study was carried out in 172 healthy middle aged subjects from South Australia. Blood levels of magnesium, Hcy, folate and vitamin B12 were measured. Cytokinesis-Block Micronucleus cytome assay was performed to measure three DNA damage biomarkers: micronuclei (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBuds) in peripheral blood lymphocytes.ResultsData showed that magnesium and Hcy are significantly inversely correlated with each other (r = − 0.299, p < 0.0001). Furthermore, magnesium is positively correlated both with folate (p = 0.002) and vitamin B12 (p = 0.007). Magnesium is also significantly inversely correlated with MN (p < 0.0001) and NPB (p < 0.0001). Individuals with low magnesium and high Hcy exhibited significantly higher frequency of MN and NPBs compared to those with high magnesium and low Hcy (p < 0.0001). Furthermore, there was an interactive effect between these two factors as well in inducing MN (p = 0.01) and NPB (p = 0.048).ConclusionsThe results obtained in the present study indicate for the first time that low in vivo levels of magnesium either on its own or in the presence of high Hcy increases DNA damage as evident by higher frequencies of MN and NPBs.

Characterisation, antibacterial and antioxidant effects of mountain tea (Sideritis L.) mediated silver nanoparticles in preventing DNA damage

Characterisation, antibacterial and antioxidant effects of mountain tea (Sideritis L.) mediated silver nanoparticles in preventing DNA damage

#2432 DNA damage analysis with oxidative stress index in patients developing contrast nephropathy after coronary angiography

Abstract Background and Aims Contrast Nephropathy (KN) is acute kidney injury that occurs after exposure to contrast material. Advanced age, chronic kidney disease, heart failure, anemia, hypertension, diabetes mellitus, and hyperuricemia have been reported in the literature to increase the risk of KN development. In addition, oxygen radicals have an important place in the pathogenesis of contrast nephropathy development. Specific biomarkers are used in clinics to determine oxidative stress and antioxidant status. In particular, measurement of total antioxidant status (TAS) and total oxidant status (TOS) can provide useful information about an individual's overall serum antioxidative status. The ratio of TOS to TAS level gives the oxidative stress index (OSI). One of the most investigated metabolites for DNA damage is 8-hydroxy-2-deoxyguanosine (8-OhdG), which is accepted as a biomarker of oxidative damage to DNA. In our study, we planned to investigate DNA damage and important predisposing factors for contrast nephropathy using oxidative stress markers. Method Between February 2021 and April 2022, blood was taken from 191 patients who underwent coronary angiography (CAG) by the Cardiology Department at ESOGU before CAG and at 72 hours after CAG. Patients who met the criteria for contrast nephropathy development (those with a serum creatinine increase of 25% or more compared to baseline or an increase of 0.5 mg/dl or more) were included as the case group in our study. Our study is a prospective study consisting of 85 cases and 106 controls, totaling 191 participants. TAS, TOS, OSI, and 8-OhDG levels were compared between both groups and before-after procedure. This study was supported by ESOGU BAP project number 1621. Results The mean age of the developing group was calculated as 68.13 ± 10.37, while it was calculated as 61.03 ± 9.97 in the control group (p = 0.00). In the case group, there were 30 (35.3%) without heart failure, while there were 75 (70.8%) without heart failure in the control group (p = 0.00). In univariate analyzes, we found that advanced age and heart failure were the most important indicators for KMN. When we compared those with and without KMN, we saw that TOS values decreased less in the group with post-angiography nephropathy than in those without it. We found a positive correlation between uric acid and TAS. In the KMN group, it was found that there was a statistically significant increase in TAS value after CAG, while there was a decrease in OSI value, and no statistically significant difference was found for TOS and 8-OhDG. In patients who underwent percutaneous intervention, it was found that there was a statistically significant increase in TAS value after CAG, while TOS and OSI decreased, and no significant difference was found for 8-OhDG. Conclusion Although previous studies have shown that oxidative stress plays an important role in contrast nephropathy pathogenesis, a strong relationship between KMN development and oxidative stress could not be found in our study. Our study is the first study to examine DNA damage with 8-OhDG in KMN, and it has been shown that there is no increase in DNA damage with KMN development. It is thought that one of the reasons leading to this result may be that contrast agents used today are selected as less toxic substances used in less volumes during processing, which may prevent DNA damage from occurring. Another result reached in our study is that TAS level increased in patients undergoing percutaneous intervention, while TOS and OSI decreased; that is, revascularization can reduce TOS and ultimately oxidative status.”

GTPase activity regulates FtsZ ring positioning in Caulobacter crescentus.

Bacterial cell division is crucial for replication and requires careful coordination via proteins collectively called the divisome. The tubulin-like GTPase FtsZ is the master regulator of this process and serves to recruit downstream divisome proteins and regulate their activities. Upon assembling at mid-cell, FtsZ exhibits treadmilling motion driven by GTP binding and hydrolysis. Treadmilling is proposed to play roles in Z-ring condensation and in distribution and regulation of peptidoglycan (PG) cell wall enzymes. FtsZ polymer superstructure and dynamics are central to its function, yet their regulation is incompletely understood. We addressed these gaps in knowledge by evaluating the contribution of GTPase activity to FtsZ's function in vitro and in Caulobacter crescentus cells. We observed that a lethal mutation that abrogates FtsZ GTP hydrolysis impacts FtsZ dynamics and Z-ring positioning, but not constriction. Aberrant Z-ring positioning was due to insensitivity to the FtsZ regulator MipZ when GTPase activity is reduced. Z-ring mislocalization resulted in DNA damage, likely due to constriction over the nucleoid. Collectively, our results indicate that GTP hydrolysis serves primarily to position the Z-ring at mid-cell in Caulobacter. Proper Z-ring localization is required for effective coordination with chromosome segregation to prevent DNA damage and ensure successful cell division.

Study on isolating, breeding, and cultivation of Xylaria nigripes (Klotzsch) Cooke

The Xylaria nigripes fungus is one of the medicinal materials that was used in traditional medicine. Extracts from the mycelium and fruiting bodies of the X. nigripes showed protecting cells, preventing DNA damage, and reducing the programmed death cell rate. In this study, the fruiting bodies of the X. nigripes were collected to isolate, propagate in the liquid medium, and then cultured to induce the fruiting body formation in the rice medium. The results showed that the X. nigripes was successfully isolated on PDAY (Potato Dextrose Agar Yeast Extract) medium, and the mycelium and spore of the X. nigripes had unique characteristics of the species. The biomass of X. nigripes grew well in a liquid nutrient medium containing 20g glucose, 1g MgSO4.7H2O, 2g KH2PO4, and 5g peptone, reaching the best mass after 21 to 28 days. Using an initial cultured liquid of X. nigripes to culture on rice medium, fruiting bodies were formed and developed after 14 days of culture. This result could potentially be applied to the production of X. nigripes biomass via mycelium and fruit bodies for application in medicine.

Exploring MTH1 inhibitory potential of Thymoquinone and Baicalin for therapeutic targeting of breast cancer

Cancers frequently have increased ROS levels due to disrupted redox balance, leading to oxidative DNA and protein damage, mutations, and apoptosis. The MTH1 protein plays a crucial role by sanitizing the oxidized dNTP pools. Hence, cancer cells rely on MTH1 to prevent the integration of oxidized dNTPs into DNA, preventing DNA damage and allowing cancer cell proliferation. We have discovered Thymoquinone (TQ) and Baicalin (BC) as inhibitors of MTH1 using combined docking and MD simulation approaches complemented by experimental validations via assessing binding affinity and enzyme inhibition. Docking and MD simulations studies revealed an efficient binding of TQ and BC to the active site pocket of the MTH1, and the resultant complexes are appreciably stable. Fluorescence measurements estimated a strong binding affinity of TQ and BC with Ka 3.4 ×106 and 1.0 ×105, respectively. Treating breast cancer cells with TQ and BC significantly inhibited the growth and proliferation (IC50 values 28.3 µM and 34.8 µM) and induced apoptosis. TQ and BC increased the ROS production in MCF7 cells, imposing substantial oxidative stress on cancer cells and leading to cell death. Finally, TQ and BC are proven strong MTH1 inhibitors, offering promising prospects for anti-cancer therapy.