Oxidative DNA Damage Research Articles

Astaxanthin‐S‐Allyl Cysteine Ester Protects Pancreatic β‐Cell From Glucolipotoxicity by Suppressing Oxidative Stress, Endoplasmic Reticulum Stress and mTOR Pathway Dysregulation

ABSTRACTGlucolipotoxicity (GLT) has emerged as established mechanism in the progression of diabetes. Identifying compounds that mitigate GLT‐induced deleterious effect on β‐cells are considered important strategy to overcome diabetes. Hence, in the present study, astaxanthin‐s‐allyl cysteine (AST‐SAC) diester was studied against GLT in β‐cells. Mus musculus pancreatic β‐cell line (βTC‐tet) was treated with high glucose (25 mM; HG) and 95 μM palmitate (PA) for 24 h to induce GLT. AST‐SAC at various concentrations (5, 10, and 15 μg/ml) were treated to understand the protective effect against HG + PA exposure in β‐cells. Under HG + PA exposure conditions oxidative stress, deregulation of mTOR pathway and endoplasmic reticulum (ER) stress are witnessed. AST‐SAC treatment eased oxidative stress, mitochondrial depolarization, DNA damage, calcium overload and accumulation of autophagosome against HG + PA exposure conditions thereby protected the cell viability of β‐cells. AST‐SAC maintained the level of proteins involved in mTOR pathway under HG + PA exposure conditions. Also, AST‐SAC treatment has mitigated the increased expression of genes and proteins such as IRE1 and PERK involved in ER stress‐mediated unfolded protein response (UPR) signaling pathways. In correspondence to it, the expression of genes involved in insulin secretion was preserved by AST‐SAC. Due to these protective effects of AST‐SAC the insulin secretion was well‐maintained in β‐cells under HG + PA exposure conditions. AST‐SAC through normalizing antioxidant status and mTOR axis as well as preventing the harmful effect of ER‐stress mediated UPR pathway has promoted the β‐cell survival and insulin secretion against GLT. Simultaneously targeting oxidative stress/mTOR axis/ER stress is required to efficiently overcome GLT in β‐cells.

Abstract A017: HER2 overexpression initiates breast tumorigenesis non-cell-autonomously by altering energy metabolism in the tissue microenvironment

Abstract Breast cancer is the most common cancer globally, with approximately 70% of pre-malignant breast tumors, known as ductal carcinoma in situ (DCIS), and 20% of invasive breast tumors overexpressing human epidermal growth factor receptor 2 (HER2). While the biological role of HER2 in invasive breast cancer has been extensively studied, its impact on breast cancer stem cells (BCSCs) and early-stage tumorigenesis, particularly within the tumor microenvironment, remains unclear. Here, we explore the role of HER2 overexpression in driving cellular events within the tumor microenvironment during the premalignant stage of breast tumorigenesis, using in vitro, in vivo, and ex vivo models. We conducted multi-omics analyses on mammary ducts from a HER2+ breast cancer mouse model at the pre-cancerous stage. Our results showed that HER2/Neu overexpression alters glucose and lipid metabolism and pentose phosphate pathway in mammary epithelial cells. Ex vivo organ culture of mammary ducts confirmed that these metabolic changes lead to increased reactive oxygen species (ROS) levels within the tumor microenvironment suggesting that oxidative stress and subsequent DNA damage are early events in HER2-driven tumorigenesis. Immunostaining of histological sections from mouse mammary glands further revealed that elevated oxidative stress and DNA damage not only in HER2+ cells but also in neighboring HER2- cells. Moreover, whole genome sequencing of tumor cells confirmed that both HER2+ and HER2- tumor cells have similar mutational burden. This suggests a non-cell-autonomous effect, where HER2 overexpression in one cell population affects the tumor microenvironment and adjacent cells, contributing to early-stage cancer development. To investigate the involvement of BCSCs during tumor initiation, we performed mammosphere assays on primary cells from HER2+ mouse models and clinical DCIS samples. Our findings showed that neither BCSCs nor their cells of origin express HER2 in both DCIS samples and murine mammary glands and tumors. This suggests that HER2 overexpression may not directly drive BCSC formation but rather creates a genotoxic microenvironment that facilitates the transformation of HER2- cell populations through a non-cell-autonomous mechanism. In summary, our findings indicate that HER2 overexpression contributes to the creation of a genotoxic tumor microenvironment by altering cellular energy metabolism and increasing ROS levels. This, in turn, may lead to the transformation of BCSCs in HER2- cell populations during early breast tumorigenesis. Understanding the role of HER2 overexpression in shaping the tumor microenvironment could provide new insights into therapeutic and preventive strategies against breast cancer. Citation Format: Sevim B. Gurler, Oliver Wagstaff, Lili Dimitrova, Fuhui Chen, Robert Pedley, William Weston, Ian J. Donaldson, Brian A. Telfer, David Novo, Kyriaki Pavlou, George Taylor, Yaqing Ou, Kaye Williams, Andrew Gilmore, Keith Brennan, Ahmet Ucar. HER2 overexpression initiates breast tumorigenesis non-cell-autonomously by altering energy metabolism in the tissue microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A017.

A multi-scale integrative approach to study the impact of a common pesticide, the dimethoate, on a mangrove fiddler crab Tubuca urvillei.

At land-sea interface, mangroves are likely to be exposed to pesticides due to agricultural run-offs. In Mayotte Island (Comoros archipelago, Mozambique Channel), dimethoate (DMT) is found in high concentrations in tomatoes, but no data confirm its presence in mangroves. We aimed at screening the presence of DMT in three mangroves of Mayotte at different levels (highest point above crops, village, upstream mangrove, downstream mangrove) and assessing the impact of DMT coupled with reduced salinity on mangrove crab physiology. To do so, we performed 24-h exposures at sublethal concentrations (10 and 100µg L-1) corresponding to 100 × and 1000 × the environmental standard (no data exist on environmental concentrations), in seawater (SW) and diluted SW (dSW). We exposed male fiddler crab Tubuca urvillei, one of the most common fiddler crabs living in mangrove areas regularly flooded and exposed to agricultural run-offs. Different physiological endpoints were considered: behaviour, acetylcholinesterase (AChE) activity, muscle energy metabolism, DNA oxidative damage and osmoregulatory capacity using hemolymph samples, posterior gills and claw muscle. We confirmed the presence of DMT in one mangrove and the effect of pesticide exposure at the different endpoints. Changes in behavioural and physiological parameters highlighted in this study could warn us of recent pesticide use upstream and help us understand past or future community-level changes in mangrove ecosystems affected by pesticide inputs.

Mitochondrial reactive oxygen species-mediated fibroblast activation has a role in tumor microenvironment formation in radiation carcinogenesis.

Cancer risks attributable to low-dose and low-dose-rate radiation are a serious concern for public health. Radiation risk assessment is based on lifespan studies among Hiroshima-Nagasaki A-bomb survivors; however, there are statistical limitations due to a small sample size for low-dose radiation. Therefore, basic biological studies are helpful in understanding the mechanism of radiation carcinogenesis. The detrimental effects of ionising radiation (IR) are caused by reactive oxygen species (ROS)-mediated oxidative DNA damage. IR-induced delayed ROS are produced in the electron transport chain reaction of the mitochondrial complex. Thus, mitochondria are a source of ROS and a primary target for ROS attacks. Consequently, mitochondrial dysfunction is thought to be a key event in the metabolic changes of cancer cells and is important in radiation-induced carcinogenesis. In this paper, we present recent findings on radiation carcinogenesis effect assessment, focusing on mitochondrial function as stress sensors.

Abstract 4137913: Role of serial evaluation of myocardial inflammatory activity and oxidative stress in determining the therapeutic efficacy of immunosuppression and clinical outcome in patients with cardiac sarcoidosis

Background: Cardiac sarcoidosis (CS) was characterized by formation of granulomas in the heart. Enhancement in myocardial inflammatory activity and oxidative stress is a crucial cause of major cardiovascular adverse events (MACE). Although immunosuppressive therapy is recommended for active CS, there is no established markers for treatment and prognosis. Hypothesis: We hypothesized that the inflammation and oxidative stress in heart were associated with MACE after steroid therapy. Aims: We identified prognostic markers for MACE in patients with CS after steroid therapy. Methods: This study was a prospective observational cohort study. Patients with CS diagnosed according to Japanese criteria were enrolled in this study. Patients with abnormal accumulation of 18 F-FDG in heart were treated with steroids with standard guideline-recommended protocol. 18 F-FDG PET were performed after more than 6 months of induction. Urinary 8-hydroxy-2'-deoxyguanosine (U-8-OHdG), a marker of oxidative DNA damage, and indices of cardiac and renal function were measured. The major outcome was a composite of the first sustained ventricular tachycardia (sVT) /sudden cardiac death (SCD), hospitalization for heart failure, and radiological relapse with exacerbation of clinical manifestation. Results: Fifty consecutive patients with CS underwent steroid therapy and followed up (median follow-up period of 58 months). 39 of 50 patients underwent 18F-FDG PET/CT more than 6 months after steroid therapy. During the follow-up period, 17 of 39 patients showed MACE, consisting of sVT/SCD (N= 11), hospitalization (N= 2) and radiological relapse (N= 4). A Cox proportional-hazard model showed that the U-8-OHdG and SUV max value of FDG-PET were independent predictors of MACE. ROC analysis revealed that the cut-off values of U-8-OHdG and SUV max for predicting the MACE were 11.6 ng/mg Cr (AUC 0.913, sensitivity 86.7%, specificity 90.0%) and 4.64 (AUC 0.878, sensitivity 76.5%, specificity 91.0%), respectively (Fig.1). Patients with a U-8-OHdG ≧11.6 ng/mg Cr or SUV max ≧4.64 had a significantly higher MACE risk (P values for U-8-OHdG and SUV max were both 0.001 by Log Rank analysis) (Fig.2). It is noted that U-8-OHdG <11.6 ng/mg Cr and SUV max <4.64 after steroid therapy indicate the good responses to the immunosuppressive therapy and better prognosis (Fig.3). Conclusion: U-8-OHdG and SUV max may be useful markers in determining the therapeutic efficacy and clinical outcome in patients with CS.

L-Tryptophan improves the sperm quality of threatened Abant trout (Salmo abanticus) against glyphosate toxicity: impact on oxidative stress and DNA damage

The current study focused on the ameliorating impact of TRP (5 mM) on Salmo abanticus spermatozoa exposed to sub‑lethal concentrations of GLY (2.5, 5, and 10 mg/L). Sperm quality parameters, oxidative stress indices, and DNA damage were analyzed in the post‑exposure sperm. Our data reveal that GLY has an adverse effect on motility rate and duration, sperm kinetics parameters, antioxidant status and DNA damage, and triggers antioxidant defense mechanisms at the highest dose (10 mg/L) and it has insufficient therapeutic effect. Overall, GLY poses potential hazards to male reproductive cells and may adversely affect subsequent generations of natural populations.

Assessing the effects of cadmium on antioxidant enzymes and histological structures in rainbow trout liver and kidney

Cadmium contamination in aquatic environments poses severe risks to aquatic organisms, particularly fish, where cadmium accumulation in tissues can lead to compromised organ functionality and reproductive issues. The present study aimed to assess the effects of cadmium (Cd) exposure on key biomarkers of oxidative stress, DNA damage, apoptosis, and enzyme activity in the liver and kidney tissues of rainbow trout (Oncorhynchus mykiss). Specifically, the study measured 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, caspase-3 activation, acetylcholinesterase (AChE) activity, and oxidative stress indicators (ONOO−, MDA, GSH, SOD, and CAT) following exposure to three Cd concentrations (1, 3, and 5 mg/L) over three time points (24, 48, and 96 h). Tissue samples were collected post-exposure, and the analysis revealed a significant decrease in MDA levels in both tissues. GSH concentrations declined with prolonged exposure, while SOD activity increased, indicating a response to oxidative stress, contrasted by a reduction in CAT activity. An initial increase in ONOO− levels was observed at 24 h, followed by a subsequent decrease at the 48 and 96 h marks. These results suggest that cadmium induces oxidative stress in the liver and kidney tissues of fish. Cadmium exposure also significantly elevated 8-OHdG levels, signaling DNA damage, and increased caspase-3 activity, indicative of apoptosis, across all doses and time points (p < 0.05). The histological examination of liver and kidney showed tissue injury. Additionally, a negative correlation between AChE activity and exposure duration was noted, with prolonged exposure resulting in substantial AChE inhibition. Given the role of AChE in behavior regulation, these findings underscore the importance of exploring time-dependent, tissue-specific changes in AChE activity to further elucidate the mechanisms underlying cadmium-induced behavioral abnormalities.

Domoic Acid: A Review of Its Cytogenotoxicity Within the One Health Approach

In this review, we toxicologically assessed the naturally occurring toxin domoic acid. We used the One Health approach because the impact of domoic acid is potentiated by climate change and water pollution on one side, and reflected in animal health, food security, human diet, and human health on the other. In a changing environment, algal blooms are more frequent. For domoic acid production, the growth of Pseudo-nitzschia diatoms is of particular interest. They produce this toxin, whose capability of accumulation and biomagnification through the food web impacts other organisms in the ecosystem. Domoic acid targets nervous system receptors inducing amnestic shellfish poisoning, among other less severe health-related problems. However, the impact of domoic acid on non-target cells is rather unknown, so we reviewed the currently available literature on cytogenetic effects on human and animal cells. The results of different studies indicate that domoic acid has the potential to induce early molecular events, such as oxidative imbalance and DNA damage, thus posing an additional threat which needs to be thoroughly addressed and monitored in the future.

Evaluation of the cell death markers for aberrated cell free DNA release in high altitude pulmonary edema.

The effect of high altitude (HA, altitude >2500 m) can trigger a maladaptive response in unacclimatized individuals, leading to various HA illnesses such as high altitude pulmonary edema (HAPE). The present study investigates circulating cell free (cf) DNA, a minimally invasive biomarker that can elicit a pro-inflammatory response. Our earlier study observed altered cfDNA fragment patterns in HAPE patients and the significant correlation of these patterns with peripheral oxygen saturation levels. However, the unclear release mechanisms of cfDNA in circulation limit its characterization and clinical utility. The present study not only observed a significant increase in cfDNA levels in HAPE patients (27.03 ± 1.37 ng/ml; n = 145) compared to healthy HA sojourners (controls, 14.57 ± 0.74 ng/ml; n = 65) and highlanders (HLs, 15.50 ± 0.8 ng/ml; n = 34) but also assayed the known cell death markers involved in cfDNA release at HA. The study found significantly elevated levels of the apoptotic marker, annexin A5, and secondary necrosis or late apoptotic marker, High mobility group box 1, in HAPE patients. In addition, we observed ahigher oxidative DNA damage marker, 8-hydroxy-2'-deoxyguanosine, in HAPE compared to controls, suggestive of the role of oxidative DNA status in promoting the inflammatory potential of cfDNA fragments and their plausible role in manifesting HAPE pathophysiology. Extensive in vitro future assays can confirm theimmunogenic role of cfDNA fragments that may act as a danger-associated molecular pattern and associate with markers of cellular stresses in HAPE.

Upregulation of ACSL, ND75, Vha26 and sesB genes by antiepileptic drugs resulted in genotoxicity in drosophila.

Clobazam (CLB) and Vigabatrin (VGB) are commonly used antiepileptic drugs (AEDs) in the treatment of epilepsy. Here, we have examined the genotoxic effect of these AEDs in Drosophila melanogaster. The Drosophila larvae were exposed to different concentrations of CLB and VGB containing food media. The assessment encompassed oxidative stress, DNA damage, protein levels, and gene expression profiles. In the CLB-treated group, a reduction in reactive oxygen species (ROS) and lipid peroxidation (LPO) levels was observed, alongside increased levels of superoxide dismutase (SOD), catalase (CAT), and nitric oxide (NO). Conversely, the VGB-treated group displayed contrasting results, with increased ROS and LPO and decreased SOD, CAT, and NO levels. However, both CLB and VGB induced DNA damage in Drosophila. Proteomic analysis (SDS-PAGE and OHRLCMS) in the CLB and VGB groups identified numerous proteins, including Acyl-CoA synthetase long-chain, NADH-ubiquinone oxidoreductase 75kDa subunit, V-type proton ATPase subunit E, ADP/ATP carrier protein, malic enzyme, and DNA-binding protein modulo. These proteins were found to be associated with pathways like growth promotion, notch signaling, Wnt signaling, neuromuscular junction (NMJ) signaling, bone morphogenetic protein (BMP) signaling, and other GABAergic mechanisms. Furthermore, mRNA levels of ACSL, ND75, Vha26, sesB, and Men genes were upregulated in both CLB and VGB-treated groups. These findings suggest that CLB and VGB could have the potential to induce genotoxicity and post-transcriptional modifications in humans, highlighting the importance of monitoring their effects when used as AEDs.

Protective Effect of Biochanin A on Gamma Radiation-Induced Oxidative Stress, Antioxidant Status, Apoptotic, and DNA Repairing Molecules in Swiss Albino Mice.

Radiation therapy is indispensable in medical practice but often causes adverse effects on healthy tissues, necessitating the search for natural radioprotectors. This study investigates the protective effect of Biochanin A (BCA) against gamma radiation-induced oxidative stress and DNA damage in Swiss albino mice. Gamma radiation, a potent ionizing source, generates reactive oxygen species (ROS) that damage cellular biomolecules, including DNA. Antioxidants play a crucial role in neutralizing ROS and preventing oxidative damage. Swiss albino mice were divided into control, BCA control (10 mg/kg body weight), radiation alone (7 Gy), and radiation+ BCA pretreatment groups. BCA, a natural isoflavone with known antioxidant and cytoprotective properties, was administered intraperitoneally before radiation exposure. After irradiation, lipid peroxidation levels, antioxidant enzyme activities/level (superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione), expression levels of DNA repair genes (P53, P21, GADD45α), apoptotic markers (Bax, Bcl-2, Caspase-3, -9 and Cytochrome-C), and inflammatory marker (NF-κB) were analyzed in small intestine tissue. Our findings indicate that gamma radiation significantly elevated lipid peroxidation levels and altered antioxidant enzyme activities, indicating oxidative stress. However, BCA pretreatment mitigated these effects by bolstering antioxidant defences, reducing radiation-induced oxidative damage. Additionally, BCA altered apoptotic markers, NF-κB expression, promoting cell survival mechanisms. At the molecular level, BCA pretreatment upregulated key DNA repair genes (P53, P21, GADD45α), crucial for repairing radiation-induced DNA damage and maintaining genomic stability. These results underscore BCA potential as a radioprotector, suggesting its efficacy in mitigating radiation-induced oxidative stress and preserving cellular integrity. In conclusion, BCA demonstrates promising radioprotective properties by attenuating oxidative stress, enhancing antioxidant defences, modulating apoptotic pathways, and promoting DNA repair mechanisms following gamma radiation exposure. Further research is necessary to elucidate its precise mechanisms of action and explore its potential therapeutic applications in radiation oncology and environmental radioprotection.

Assessing the Potential Dangers of Cell Phone Use to Human Health: A Review of the Evidence on Cancer Risk

Cell phones have become ubiquitous in modern life, leading to concerns about potential health risks associated with prolonged exposure to radiofrequency electromagnetic fields (RF-EMF) emitted by these devices. This review examines the current scientific evidence on the potential link between cell phone use and cancer risk, focusing on epidemiological studies, experimental research, and mechanistic investigations. Epidemiological studies, including large-scale cohort studies and case-control studies, have produced mixed results, with some indicating possible associations between cell phone use and specific cancers such as glioma and acoustic neuroma, while others find no significant link. Experimental research has explored potential biological mechanisms, such as oxidative stress and DNA damage, but definitive connections to cancer remain elusive. Regulatory perspectives and public health recommendations emphasize cautious use, particularly among vulnerable populations. Despite extensive research, significant gaps remain, including limited long-term data and inadequate exploration of new technologies like 5G. Future research should address these gaps through long-term, interdisciplinary studies and improved exposure assessment methods. This review highlights the complexity of the issue and underscores the need for ongoing research to provide clearer insights and inform public health guidelines. Keywords: Cell phone use, cancer risk, radiofrequency electromagnetic fields (RF-EMF), epidemiological studies.

Quercetin has a protective impact on human umbilical vein endothelial cells against tungsten carbide cobalt nanoparticle-induced cytotoxicity, oxidative stress, apoptosis

Oxidative stress is a pivotal factor in the pathogenesis of various cancer diseases. In fact, oxidative DNA damage is described as the type of damage probably to occur in cancer cells. This study examined the protective impact of the polyphenolic compound quercetin on human umbilical vein endothelial (HUVEC) cells against tungsten carbide cobalt nanoparticles (WC-Co NPs)-induced oxidative stress, cytotoxicity, and apoptosis. One of the most often used models for studying endothelial cells in vitro is the human umbilical vein epithelial cell. Scanning electron microscope (SEM) and transmission electron microscopy (TEM) were used to measure the size of the NPs prior to WC-Co NPs treatment. WC-Co NPs had a polygonal form and measured 45.26 ± 1 nm in size. Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT),neutral red uptake(NRU) and lactate dehydrogenase (LDH) assays, the cytotoxicity of WC-Co NPs on HUVECs cells was assessed. The cytotoxicity of NPs increased in a concentration-dependent way. The MTT result was used to calculate the median inhibitory concentration (IC50) for HUVEC cells at 24 h, which came out to be 23.14 μg/ml. Intracellular reactive oxygen species(ROS) and lipid peroxidation(LPO) levels were elevated at 17 g/ml WC-Co NPs and then reduced in HUVECs cells upon immediate exposure to 150 µM quercetin (QR). Using JC-1 staining, the loss of mitochondrial membrane potential(MMP) in control, WC-Co NPs alone and WC-Co NPs plus QR exposed cell were evaluated. In HUVECs cells, maximum apoptotic cells were seen at increasing NPs concentrations. Based on the impacts of NPs on HUVECs cells, the data suggests that QR may work on the process of scavenging ROS, which is responsible for DNA repair. Consequently, the above findings highlight the significance of these QR as defenses against DNA damage brought on by oxidative stress, which frequently happens in a number of cancer disorders.

OGG1: An emerging multifunctional therapeutic target for the treatment of diseases caused by oxidative DNA damage.

Oxidative DNA damage-related diseases, such as incurable inflammation, malignant tumors, and age-related disorders, present significant challenges in modern medicine due to their complex molecular mechanisms and limitations in identifying effective treatment targets. Recently, 8-oxoguanine DNA glycosylase 1 (OGG1) has emerged as a promising multifunctional therapeutic target for the treatment of these challenging diseases. In this review, we systematically summarize the multiple functions and mechanisms of OGG1, including pro-inflammatory, tumorigenic, and aging regulatory mechanisms. We also highlight the potential of OGG1 inhibitors and activators as potent therapeutic agents for the aforementioned life-limiting diseases. We conclude that OGG1 serves as a multifunctional hub; the inhibition of OGG1 may provide a novel approach for preventing and treating inflammation and cancer, and the activation of OGG1 could be a strategy for preventing age-related disorders. Furthermore, we provide an extensive overview of successful applications of OGG1 regulation in treating inflammatory, cancerous, and aging-related diseases. Finally, we discuss the current challenges and future directions of OGG1 as an emerging multifunctional therapeutic marker for the aforementioned challenging diseases. The aim of this review is to provide a robust reference for scientific researchers and clinical drug developers in the development of novel clinical targeted drugs for life-limiting diseases, especially for incurable inflammation, malignant tumors, and age-related disorders.

Bioactive fraction of Musa balbisiana seed mitigates D-galactose-induced brain aging via SIRT1/PGC-1α/FoxO3a activation and intestinal barrier dysfunction by modulating gut microbiota and core metabolites

Aging is an inevitable biological process, and emerging research has highlighted the potential of dietary and pharmacological interventions to decelerate the trajectory of age-related diseases and prolong the health span. This study evaluates the protective effects of Musa balbisiana seed on healthy aging using D-galactose-induced accelerated aging rats. The results suggested that the bioactive ethyl acetate fraction of Musa balbisiana seed extract (BF) exhibited protective effects against aging-induced oxidative stress by reducing oxidative DNA damage, advanced glycation end-product formation, and malondialdehyde levels while restoring antioxidant and glyoxalase enzyme activities. BF also ameliorated neurodegeneration by decreasing acetylcholinesterase enzyme activity and amyloid beta plaque formation. Histopathological analysis demonstrated the protective effects of BF against brain aging, liver disruption, renal damage, and intestinal barrier dysfunction. BF further restored intestinal permeability by upregulating the tight junctions (zonula occludens 1 and 2, claudin 1,2,3 and 4, and occludin) and mucin (mucin 2 and mucin 5ac) gene expression while downregulating the expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α). BF significantly induced the phosphorylation of FoxO3a proteins and upregulated the gene expression of SIRT1, PGC-1α, and TFAM in the hippocampus. Next-generation sequencing (NGS) of 16s rRNA amplicons of fecal metagenomics DNA and metabolites profiling showed that BF intervention restructured the gut microbiota and altered core metabolites related to cholesterol metabolism. Overall, our findings demonstrated the multifaceted protective effects of Musa balbisiana seed against D-galactose-induced aging.

Sulfur-Doped g-C3N4/Polycaprolactone Nanofibers Based Smart Sensor for 8-hydroxy-2-deoxyguanosine Biomarker Monitoring

8-Hydroxy-2′-deoxyguanosine (8-OHdG) signifies one of the primary byproducts of oxidative DNA damage, thereby being a valuable DNA biomarker. This study presents a label-free, low-cost, smart sensor that could improve evaluation, tracking, and survival rates by allowing for an early assessment of cancer. Herein, we fabricated sulfur-doped graphitic carbon nitride (S-gC₃N₄) embedded in polycaprolactone (PCL) for highly efficient monitoring of 8-OHdG, offering functional groups such as sulfur and nitrogen that facilitate strong binding against 8-OHdG. FTIR, XRD, and SEM techniques were utilized to investigate the S-gC3N4/PCL nanocomposite. Interestingly, the nanocomposite demonstrates strong electrochemical responses to the oxidation of 8-OHdG, with a detection limit of 0.24 nM across a wide dynamic concentration range (1 nM–50 μM). Additionally, it exhibits exceptional durability, selectivity, reusability, and repeatability. Additionally, the designed sensor has the potential to measure 8-OHdG levels in individuals and could be used to evaluate early cancer indicators. Furthermore, the S-gC₃N₄/PCL sensor was successfully tested to determine 8-OHdG levels in human samples.

Investigation of the acute effect of the synthetic hemodialysis membrane on the expression of XRCC1 and PARP1 in chronic hemodialysis patients.

The interaction between blood from end-stage renal failure patients undergoing hemodialysis treatment and the hemodialysis (HD) membranes used may lead to DNA damage, contingent upon the biocompatibility of the membranes. Given that this process could impact the disease's course, it is crucial to assess the efficacy of DNA repair mechanisms. In our study, we investigated the gene expression levels of XRCC1 and PARP1 enzymes, which are involved in the base excision repair (BER) repair mechanism crucial for repairing oxidative DNA damage, in 20 end-stage renal disease (ESRD) patients undergoing HD treatment both before and after dialysis sessions. Additionally, we compared our findings with those from 20 healthy controls. We assessed gene expression levels using real-time polymerase chain reaction (qRT-PCR). We observed that the HD process utilizing a polysulfone membrane did not impact the expression levels of genes. However, we noted a lower expression level of the PARP1 gene in ESRD patients undergoing HD compared to the control group (0.021 ± 0.005 vs 0.0019 ± 0.0013, p = 0.0001). Although our study findings indicate that HD membranes do not affect gene expression overall, the specific decrease in PARPI gene expression suggests that the effectiveness of the BER DNA repair mechanism is impaired in ESRD patients, which may play a significant role in the progression of the disease.

Evaluation of Some Immunological and DNA Damage Parameters among Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) can cause permanent joint damage and disability through inflammation in the joints. Other organs, such as blood vessels, lungs, heart, eyes and skin may also get affected. This study aimed to evaluate the changes of some oxidative stress markers including oxidative DNA damage and the clinical outcomes that are associated with Iraqi rheumatoid arthritis patients. Commercial enzyme linked immunosorbent assay (ELISA) kits were applied to evaluate malondialdehyde (MDA), DNA damage marker 8-hydroxy-2-deoxyguanosine (8-OHDG), and glutathione peroxidase 3 (GPX3) levels in serum of 60 patients having RA with ages ranging between 20-70 years and 30 age-matched healthy controls. The results showed a significant increase in MDA levels in RA patients compared with the control group. Also, the levels of GPX3 decreased in RA patients with highly significant differences as compared with healthy control. Highly significant serum levels of oxidative DNA damage in RA patients were observed compared to the control group. Body Mass Index (BMI) results indicted significant differences between RA patients and healthy control. It can, therefore, be concluded that there is a potential role if malondialdehyde, oxidative DNA damage and GPX3 are used as biomarkers for progression of in patients with RA.

Rewiring the nexus between urban traffic pollution-derived polycyclic aromatic hydrocarbon exposure and DNA injury via urinary metabolomics

Urban road traffic environmental stress impacts outdoor population health, with oxidative damage serving as an early indicator of xenobiotic exposure. Polycyclic aromatic hydrocarbons (PAHs) as priority carcinogens pose significant public health burden, yet knowledge remains limited regarding the endogenous metabolic alternations associated with oxidative DNA injury. This cross-sectional study focused on the cohort consisting of 109 sanitation workers (“traffic exposure group”) and 112 demographics-matched common residents (“controls”) in South China. The goal was to elucidate the occurrence of internal exposure to nine hydroxyl PAHs, and the interrelations with oxidative DNA damage (indicated by 8-hydroxy-2′-deoxyguanosine, 8-OHdG) by linear mixed-effect regression model. T-test and orthogonal partial least squares discriminant analysis were used to determine differential metabolites in non-targeted metabolomics. Results revealed outdoor workers suffered from the heavier PAH exposure burden and exhibited a stronger dose-dependent correlation with 8-OHdG, evidenced by the higher regression coefficient (0.244, 95% CI: 0.154–0.334) than controls (0.203, 95% CI: 0.079–0.328). In total 42 differential endogenous metabolites witnessed significant expression under traffic emission scenario, mainly implicated in phenylalanine, tyrosine and tryptophan biosynthesis. The down-expressed uric acid was the unique metabolite that inversely correlated with the increased intake of ∑8PAH especially in cases. Partially attributed to the traffic-derived PAHs, the dysregulated amino acid, nicotinamide, purine, and steroid hormones metabolic pathways encompassing 11 metabolites were determined as underlying biomarkers in mediating DNA damage. Notably, our findings proposed uric acid may act as a potential antioxidant, as evidenced by the negative correlation with 8-OHdG. The study illustrates outcomes of metabolomics can collaboratively indicate DNA oxidative damage caused by PAHs linked to urban traffic exposure, which holds significant implications for future toxicological research.

Human adipose and umbilical cord mesenchymal stem cell-derived extracellular vesicles mitigate photoaging via TIMP1/Notch1

UVB radiation induces oxidative stress, DNA damage, and inflammation, leading to skin wrinkling, compromised barrier function, and an increased risk of carcinogenesis. Addressing or preventing photoaging may offer a promising therapeutic avenue for these conditions. Recent research indicated that mesenchymal stem cells (MSCs) exhibit significant therapeutic potential for various skin diseases. Given that extracellular vesicles (EV) can deliver diverse cargo to recipient cells and elicit similar therapeutic effects, we investigated the roles and underlying mechanisms of both adipose-derived MSC-derived EV (AMSC-EV) and umbilical cord-derived MSC-derived EV (HUMSC-EV) in photoaging. Our findings indicated that in vivo, treatment with AMSC-EV and HUMSC-EV resulted in improvements in wrinkles and skin hydration while also mitigating skin inflammation and thickness alterations in both the epidermis and dermis. Additionally, in vitro studies using human keratinocytes (HaCaTs), human dermal fibroblast cells (HDFs), and T-Skin models revealed that AMSC-EV and HUMSC-EV attenuated senescence, reduced levels of reactive oxygen species (ROS) and DNA damage, and alleviated inflammation induced by UVB. Furthermore, EV treatment enhanced cell viability and migration capacity in the epidermis and promoted extracellular matrix (ECM) remodeling in the dermis in photoaged cell models. Mechanistically, proteomics results showed that TIMP1 was highly expressed in both AMSC-EV and HUMSC-EV and could exert similar effects as MSC-EV. In addition, we found that EV and TIMP1 could inhibit Notch1 and downstream targets Hes1, P16, P21, and P53. Collectively, our data suggests that both AMSC-EV and HUMSC-EV attenuate skin photoaging through TIMP1/Notch1.