Search Results (44)

Background/Objectives: Emerging evidence implicates impaired DNA repair mechanisms in the pathogenesis of Parkinson’s disease (PD), particularly in the context of oxidative stress and environmental exposures. This study investigated the association between five polymorphisms in nucleotide excision repair (NER) pathway genes and PD susceptibility in a northern Mexican mestizo population. Methods: We conducted a case–control study including 137 patients with clinically diagnosed PD and 137 age- and sex-matched controls. Genomic DNA was isolated from peripheral blood, and genotyping of ERCC1 (rs11615), ERCC2 (rs13181), XPA (rs1800975), XPC (rs2228001), and XPF (rs1799801) was performed using TaqMan real-time PCR assays. Associations between genotype frequencies and PD were evaluated using logistic regression models adjusted for age, sex, and pesticide exposure. Results: A significantly higher prevalence of pesticide exposure was observed in PD patients than in controls (OR 2.08, 95% CI 1.18–3.68; p = 0.01). The XPC rs2228001 C/C genotype was independently associated with increased PD risk in males (OR 3.25, 95% CI 1.07–9.85; p = 0.042), even after adjusting for uric acid, pesticide exposure, and cognitive status (MMSE score). No significant associations were found for other NER-related polymorphisms. Male PD patients also exhibited significantly lower serum uric acid levels than controls (p = 0.046), supporting a link between oxidative stress and disease vulnerability. Conclusions: Our findings suggest a sex-specific genetic contribution to PD susceptibility involving the XPC rs2228001 variant, particularly in the context of pesticide exposure. These results underscore the relevance of DNA repair pathways in PD pathogenesis and highlight the importance of integrated models incorporating genetic and environmental risk factors. Full article

Biogas plants for sewage and organic waste treatment are rapidly expanding. While these facilities provide valuable benefits, such as renewable energy production and the promotion of circular economy practices, they also emit airborne particles of biological origin, which may pose potential health risks. This study aims to evaluate, by in vitro assay, the cytotoxic and genotoxic potential of PM₁₀ sub-fractions (0.49–10 µm and <0.49 µm) generated in eight different plants, also assessing the endotoxin component using the Limulus Amebocyte Lysate (LAL) assay. Human embryonic lung fibroblasts (HELF) were exposed to organic extracts of particulate matter (PM). Cytotoxic effects (XTT assay) were analyzed, along with the modulation of gene expression involved in DNA repair (ERCC1, XRCC1, XPA, and XPF) and IL-8 production as a marker of inflammatory response. PM₁₀ and endotoxin concentrations varied significantly among the plants (ANOVA, p < 0.01), with PM₁₀ levels ranging from 14 to 18,000 µg/m³ and endotoxin content from 1 to 138 EU/m³. Exposure significantly increased ERCC1 and IL-8 expression by 25% and 53%, respectively (paired t-test, p < 0.01). IL-8 expression correlated with endotoxin exposure (Spearman’s rho = 0.35; p < 0.01). A deeper understanding of the biological component of airborne PM₁₀ can enhance risk assessments for occupational and nearby resident communities’ safety. Full article

New materials are actively being developed for use in various fields of electronics, as they can significantly improve the performance of electronic devices and prevent adverse effects. Such materials include nanocomposites, which include nanoparticles of magnetic metals and alloys in a non-magnetic polymer or carbon matrix. For the first time, we synthesized FeCoSm/C nanocomposites and studied the effect of synthesis conditions on their structure, composition, and electromagnetic properties. Thermogravimetric (TG) analysis and differential scanning calorimetry (DSC) analysis of the heating processes of nanocomposite precursors allowed optimizing the mode of IR processing of precursors. X-ray phase analysis (XPA) showed that nanoparticles of a solid-metal solution based on the FeCo structure are formed, and at temperatures above 700 °C, the formation of SmCo5-x alloy nanoparticles is also possible. As the synthesis temperature increases, the average size of nanoparticles of alloys containing Sm increases. The effect of the metal ratio in the precursor on the structure, composition, and electromagnetic properties of FeCoSm/C nanocomposites is analyzed. It has been established that the most promising of all the studied materials are those obtained at a temperature of 700 °C with a metal ratio of Fe:Co:Sm = 50:40:10. Full article

In this paper, we propose the XPaC (XGBoost Prediction and Cumulative Prospect Theory (CPT)) model to minimize the operational losses of the power grid, taking into account both the prediction of electric vehicle (EV) charging demand and the associated uncertainties, such as when customers will charge, how much electric energy they will need, and for how long. Given that power utilities supply electricity with limited resources, it is crucial to efficiently control EV charging peaks or predict charging demand during specific periods to maintain stable grid operations. While the total amount of EV charging is a key factor, when and where the charging occurs can be even more critical for the effective management of the grid. Although numerous studies have focused on individually predicting EV charging patterns or demand and evaluating the effectiveness of EV charging control, comprehensive assessments of the actual operational benefits and losses resulting from charging control based on predicted charging behavior remain limited. In this study, we firstly compare the performance of LSTM (Long Short-Term Memory), GRU (Gated Recurrent Unit), and decision tree-based XGBoost regression models in predicting hourly charging probabilities and the need for grid demand control. Using the predicted results, we applied the CPT algorithm to analyze the optimal operational scenarios and assess the expected profit and loss for the power grid. Since the charging control optimizer with XPaC incorporates real-world operational data and uses actual records for analysis, it is expected to provide a robust solution for managing the demand arising from the rapid growth of electric vehicles, while operating within the constraints of limited energy resources. Full article

Background/Objective: Ultraviolet (UV) B radiation leads to DNA damage by generating cyclobutane pyrimidine dimers (CPDs). UVB-induced CPDs can also result in immune suppression, which is a major risk factor for non-melanoma skin cancer (NMSC). UVB-induced CPDs are repaired by nucleotide repair mechanisms (NER) mediated by xeroderma pigmentosum complementation group A (XPA). The purpose of this study was to investigate the use of TH as a chemopreventive agent against the development of skin cancer. Method: SKH-1 hairless mice were exposed were fed with TH (0.1% v/v) for two weeks and exposed to a single dose of UVB (180 mJ/cm²). Dorsal skin was harvested 24 h post-UVB exposure for evaluation of DNA damage and repair. Lymph nodes were also harvested to prepare single cell suspension for flow cytometric evaluation. For carcinogenesis experiments, SKH-1 hairless mice were given TH (0.1% v/v) ad libitum and exposed to UVB (180 mJ/cm²) thrice a week for 30 weeks. Results: Feeding SKH-1 hairless mice with TH (0.1% v/v) for two weeks prior to a single dose of UVB (180 mJ/cm²) led to a significant increase in XPA in skin and DNA repair cytokines IL-12 and IL-23 in draining lymph nodes. Furthermore, when subjected to the photocarcinogenesis protocol; mice fed with TH developed significantly fewer tumors in comparison to mice fed on drinking water. Conclusions: Our data demonstrate that TH has a protective effect against UVB-induced DNA damage, immune suppression, and skin cancer. Future studies will further investigate the potential of TH as a preventive treatment for NMSC. Full article

Pyrrolizidine alkaloids (PAs) are common phytotoxins that are found worldwide. Upon hepatic metabolic activation, the reactive PA metabolites covalently bind to DNAs and form DNA adducts, causing mutagenicity and tumorigenicity in the liver. However, the molecular basis of the formation and removal of PA-derived DNA adducts remains largely unexplored. In the present study, Sprague Dawley (SD) rats were exposed to retrorsine (RTS), a representative PA, at a human-relevant dose of 3.3 mg/kg/day for 28 days. The rats were divided into three groups: control, RTS-28 (sacrificed after continuous RTS exposure), and RTS-161 (sacrificed at 133 days post-RTS-exposure). The multi-omics analyses demonstrated the involvement of homologous recombination (HR) and non-homologous end joining (NHEJ) repair pathways as a response to PA-induced DNA damage. Additionally, the characteristic guanine adducts induced by RTS exposure were in accordance with the higher expression of XPA and XPC, indicating that nucleotide excision repair (NER) and base excision repair (BER) also contributed to repairing RTS-induced DNA damage. Furthermore, we also showed that DNA damage persisted after PA exposure, and mutagenically related repair errors might occur due to the prolonged genotoxic effects. The present study lays the foundation for bridging PA-derived DNA adducts, DNA damage, DNA repair, and the follow-up mutagenesis and carcinogenesis associated with PA exposure. Full article

The Chinese Tan sheep is a unique breed of sheep that is typical throughout China, mainly used for fur and meat production. They are widely distributed in northwestern China and are famous for their lambskin and shiny white curly wool. In this study, the phenotypic traits of wool length, birth weight, and head coat color were evaluated in 256 Chinese Tan sheep breeds. Whole genome sequencing generated 23.67 million high-quality SNPs for genome-wide association studies (GWAS). We identified 208 significant SNPs associated with birth wool length, implicating RAD50, MACROD2, SAMD5, SASH1, and SPTLC3 as potential candidate genes for this trait. For birth weight, 1056 significant SNPs, with 76.89% of them located on chromosome 2, were identified by GWAS, and XPA, INVS, LOC121818504, GABBR2, LOC101114941, and LOC106990096 were identified as potential candidate genes for birth weight. The GWAS for head coat color identified 1424 significant SNPs across three chromosomes, with 99.65% on chromosome 14, and SPIRE2, TCF25, and MC1R as candidate genes were found to be possibly involved in the development of the black-headed coat color in sheep. Furthermore, we selected head coat color as a representative trait and performed an independent test of our GWAS findings through multiplex PCR SNP genotyping. The findings validated five mutation sites in chromosome 14 (14,251,947 T>A, 14,252,090 G>A, 14,252,158 C>T, 14,252,329 T>G, and 14,252,464 C>T) within the exon1 of the MC1R gene (517 bp), as identified by GWAS in an additional 102 Tan sheep individuals, and revealed that black-headed sheep predominantly exhibited heterozygous genotypes, possibly contributing to their color change. Our results provide a valuable foundation for further study of these three economically important traits, and enhance our understanding of genetic structure and variation in Chinese Tan sheep. Full article

Nucleotide excision repair (NER) is the most universal repair pathway, which removes a wide range of DNA helix-distorting lesions caused by chemical or physical agents. The final steps of this repair process are gap-filling repair synthesis and subsequent ligation. XPA is the central NER scaffolding protein factor and can be involved in post-incision NER stages. Replication machinery is loaded after the first incision of the damaged strand that is performed by the XPF–ERCC1 nuclease forming a damaged 5′-flap processed by the XPG endonuclease. Flap endonuclease I (FEN1) is a critical component of replication machinery and is absolutely indispensable for the maturation of newly synthesized strands. FEN1 also contributes to the long-patch pathway of base excision repair. Here, we use a set of DNA substrates containing a fluorescently labeled 5′-flap and different size gap to analyze possible repair factor–replication factor interactions. Ternary XPA–FEN1–DNA complexes with each tested DNA are detected. Furthermore, we demonstrate XPA–FEN1 complex formation in the absence of DNA due to protein–protein interaction. Functional assays reveal that XPA moderately inhibits FEN1 catalytic activity. Using fluorescently labeled XPA, formation of ternary RPA–XPA–FEN1 complex, where XPA accommodates FEN1 and RPA contacts simultaneously, can be proposed. We discuss possible functional roles of the XPA–FEN1 interaction in NER related DNA resynthesis and/or other DNA metabolic processes where XPA can be involved in the complex with FEN1. Full article

The recurrence of diffuse large B-cell lymphoma (DLBCL) has been observed in 40% of cases. The standard of care for refractory/relapsed DLBCL (RR-DLBCL) is platinum-based treatment prior to autologous stem cell transplantation; however, the prognosis for RR-DLBCL patients remains poor. Thus, to identify genes affecting the cisplatin response in DLBCL, cisplatin-based whole-genome CRISPR-Cas9 knockout screens were performed in this study. We discovered DNA damage response (DDR) pathways as enriched among identified sensitizing CRISPR-mediated gene knockouts. In line, the knockout of the nucleotide excision repair genes XPA and ERCC6 sensitized DLBCL cells to platinum drugs irrespective of proliferation rate, thus documenting DDR as essential for cisplatin sensitivity in DLBCL. Functional analysis revealed that the loss of XPA and ERCC6 increased DNA damage levels and altered cell cycle distribution. Interestingly, we also identified BTK, which is involved in B-cell receptor signaling, to affect cisplatin response. The knockout of BTK increased cisplatin sensitivity in DLBCL cells, and combinatory drug screens revealed a synergistic effect of the BTK inhibitor, ibrutinib, with platinum drugs at low concentrations. Applying local and external DLBCL cohorts, we addressed the clinical relevance of the genes identified in the CRISPR screens. BTK was among the most frequently mutated genes with a frequency of 3–5%, and XPA and ERCC6 were also mutated, albeit at lower frequencies. Furthermore, 27–54% of diagnostic DLBCL samples had mutations in pathways that can sensitize cells to cisplatin. In conclusion, this study shows that XPA and ERCC6, in addition to BTK, are essential for the response to platinum-based drugs in DLBCL. Full article

In this study, a method for producing nitrogen-modified graphene oxide (NMGO) using hydrothermal synthesis in the presence of triethanolamine is presented. The composition and structure of NMGO are characterized using X-ray phase analysis (XPA), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and Raman spectroscopy. Ni-based metal matrix coatings (MMCs) modified with NMGO were obtained from a sulfate-chloride electrolyte in the galvanostatic mode. The process of electrochemical deposition of these coatings was studied using chronovoltammetry. The microstructure of Ni–NMGO MMCs was studied using the XPA and SEM methods. It has been established that the addition of NMGO particles into the Ni matrix results in an increase in the microhardness of the resulting coatings by an average of 1.30 times. This effect is a consequence of the refinement of crystallites and high mechanical properties of NMGO phase. The corrosion-electrochemical behavior of studied electrochemical deposits in 0.5 M sulfuric acid was analyzed. It has been shown that the corrosion rate of Ni–NMGO MMCs in a 3.5% sodium chloride environment decreases by approximately 1.50–1.70 times as compared to unmodified Ni coatings. This is due to NMGO particles that act as a barrier preventing the propagation of the corrosion and form corrosive galvanic microelements with Ni, promoting anodic polarization. Full article

Background and Objectives: Nucleotide Excision Repair (NER), the most extensively researched DNA repair mechanism, is responsible for repairing a variety of DNA damages, and Xeroderma Pigmentosum (XP) genes participate in NER. Herein, we aimed to update the previous results with a meta-analysis evaluating the association of XPA, XPB/ERCC3, XPF/ERCC4, and XPG/ERCC5 polymorphisms with the susceptibility to HNC. Materials and Methods: PubMed/Medline, Web of Science, Scopus, and Cochrane Library databases were searched without any restrictions until 18 November 2023 to find relevant studies. The Review Manager 5.3 (RevMan 5.3) software was utilized to compute the effect sizes, which were expressed as the odds ratio (OR) with a 95% confidence interval (CI). Results: Nineteen articles were involved in the systematic review and meta-analysis that included thirty-nine studies involving ten polymorphisms. The results reported that the CC genotype of rs17655 polymorphism showed a significantly decreased risk of HNC in the recessive model (OR: 0.89; 95%CI: 0.81, 0.99; p-value is 0.03). In addition, the CT genotype (OR: 0.65; 95%CI: 0.48, 0.89; p-value is 0.008) of the rs751402 polymorphism was associated with a decreased risk, and the T allele (OR: 1.28; 95%CI: 1.05, 1.57; p-value is 0.02), the TT (OR: 1.74; 95%CI: 1.10, 2.74; p-value is 0.02), and the TT + CT (OR: 2.22; 95%CI: 1.04, 4.74; p-value is 0.04) genotypes were associated with an increased risk of HNC. Conclusions: The analysis identified two polymorphisms, rs17655 and rs751402, as being significantly associated with the risk of HNC. The study underscored the influence of various factors, such as the type of cancer, ethnicity, source of control, and sample size on these associations. Full article

The landscape of chromosomal aberrations in the tumor cells of the patients with B-ALL is diverse and can influence the outcome of the disease. Molecular karyotyping at the onset of the disease using chromosomal microarray (CMA) is advisable to identify additional molecular factors associated with the prognosis of the disease. Molecular karyotyping data for 36 patients with Ph-negative B-ALL who received therapy according to the ALL-2016 protocol are presented. We analyzed copy number alterations and their prognostic significance for CDKN2A/B, DMRTA, DOCK8, TP53, SMARCA2, PAX5, XPA, FOXE1, HEMGN, USP45, RUNX1, NF1, IGF2BP1, ERG, TMPRSS2, CRLF2, FGFR3, FLNB, IKZF1, RUNX2, ARID1B, CIP2A, PIK3CA, ATM, RB1, BIRC3, MYC, IKZF3, ETV6, ZNF384, PTPRJ, CCL20, PAX3, MTCH2, TCF3, IKZF2, BTG1, BTG2, RAG1, RAG2, ELK3, SH2B3, EP300, MAP2K2, EBI3, MEF2D, MEF2C, CEBPA, and TBLXR1 genes, choosing t(4;11) and t(7;14) as reference events. Of the 36 patients, only 5 (13.8%) had a normal molecular karyotype, and 31 (86.2%) were found to have various molecular karyotype abnormalities—104 deletions, 90 duplications or amplifications, 29 cases of cnLOH and 7 biallelic/homozygous deletions. We found that 11q22-23 duplication involving the BIRC3, ATM and MLL genes was the most adverse prognostic event in the study cohort. Full article

Within the framework of this study, Ni-based composite electrochemical coatings (CECs) modified with multilayer graphene oxide (GO) processed using microwave radiation have been deposited. The process of these coatings’ electrodeposition in the potentiodynamic mode has been studied. The structure of Ni–GO and Ni–GO (MW) CECs has been studied using X-ray phase analysis (XPA) and scanning electron microscopy (SEM).It has been shown that the addition of GO into a nickel deposit contributes to the formation of uniform fine-grained coatings. As a result, the microhardness of the Ni–GO (MW) CECs increases by 1.40 times compared to Ni without GO. The corrosion–electrochemical behavior of nickel CECs in 0.5 M H₂SO₄ solution was researched. It was established that the corrosion rate of the nickel–GO (MW) CEC in 3.5% NaCl decreases by about 1.70 times in contrast to unmodified nickel coatings. This effect is due to the absence of agglomeration of the graphene oxide in the volume of the nickel matrix and the impermeability of GO particles to the corrosive environment. Full article

Cigarette smoking (CS) is a major cause of various serious diseases due to tobacco chemicals. There is evidence suggesting that CS has been linked with the DNA damage repair system, as it can affect genomic stability, inducing genetic changes in the genes involved in the repair system, specifically the nucleotide excision repair (NER) pathway, affecting the function and/or regulation of these genes. Single nucleotide polymorphism (SNP), along with CS, can affect the work of the NER pathway and, therefore, could lead to different diseases. This study explored the association of four SNPs in both XPA and XPC genes with CS in the Saudi population. The Taq Man genotyping assay was used for 220 healthy non-smokers (control) and 201 healthy smokers to evaluate four SNPs in the XPA gene named rs10817938, rs1800975, rs3176751, and rs3176752 and four SNPs in the XPC gene called rs1870134, rs2228000, rs2228001, and rs2607775. In the XPA gene, SNP rs3176751 showed a high-risk association with CS-induced diseases with all clinical parameters, including CS duration, CS intensity, gender, and age of smokers. On the other hand, SNP rs1800975 showed a statistically significant low-risk association with all clinical parameters. In addition, rs10817938 showed a high-risk association only with long-term smokers and a low-risk association only with younger smokers. A low-risk association was found in SNP rs3176752 with older smokers. In the XPC gene, SNP rs2228001 showed a low-risk association only with female smokers. SNP rs2607775 revealed a statistically significant low-risk association with CS-induced diseases, concerning all parameters, except for male smokers. However, SNP rs2228000 and rs1870134 showed no association with CS. Overall, the study results demonstrated possible significant associations (effector/and protector) between CS and SNPs polymorphisms in DNA repair genes, such as XPA and XPC, except for rs2228000 and rs1870134 polymorphisms. Full article

The hormonal form of vitamin D₃, 1,25(OH)₂D₃, reduces UV-induced DNA damage. UV exposure initiates pre-vitamin D₃ production in the skin, and continued UV exposure photoisomerizes pre-vitamin D₃ to produce “over-irradiation products” such as lumisterol₃ (L₃). Cytochrome P450 side-chain cleavage enzyme (CYP11A1) in skin catalyzes the conversion of L₃ to produce three main derivatives: 24-hydroxy-L₃ [24(OH)L₃], 22-hydroxy-L₃ [22(OH)L₃], and 20,22-dihydroxy-L₃ [20,22(OH)L₃]. The current study investigated the photoprotective properties of the major over-irradiation metabolite, 24(OH)L₃, in human primary keratinocytes and human skin explants. The results indicated that treatment immediately after UV with either 24(OH)L₃ or 1,25(OH)₂D₃ reduced UV-induced cyclobutane pyrimidine dimers and oxidative DNA damage, with similar concentration response curves in keratinocytes, although in skin explants, 1,25(OH)₂D₃ was more potent. The reductions in DNA damage by both compounds were, at least in part, the result of increased DNA repair through increased energy availability via increased glycolysis, as well as increased DNA damage recognition proteins in the nucleotide excision repair pathway. Reductions in UV-induced DNA photolesions by either compound occurred in the presence of lower reactive oxygen species. The results indicated that under in vitro and ex vivo conditions, 24(OH)L₃ provided photoprotection against UV damage similar to that of 1,25(OH)₂D₃. Full article