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Oncology Research 2024Chimeric antigen receptor T (CAR-T) cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies. However, there is an extant void in...
BACKGROUND
Chimeric antigen receptor T (CAR-T) cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies. However, there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T (CAR-T) cell therapy, as well as the optimal timing for CAR-T cell infusion post-chemotherapy.
MATERIALS AND METHODS
We employed cell-derived tumor xenograft (CDX) murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment. Furthermore, transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.
RESULTS
Our preclinical evaluation determined that a combination of cyclophosphamide and fludarabine, followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy, exerts the most efficacious therapeutic effect in B-cell hematological malignancies. Concurrently, RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism, primarily through the inhibition of key mitochondrial targets, such as C-Jun Kinase enzyme (C-JUN).
CONCLUSION
In summary, the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.
Topics: Vidarabine; Cyclophosphamide; Animals; Mice; Humans; Immunotherapy, Adoptive; Antigens, CD19; Xenograft Model Antitumor Assays; Receptors, Chimeric Antigen; Hematologic Neoplasms; Cell Line, Tumor; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy
PubMed: 38827326
DOI: 10.32604/or.2024.049792 -
Antiviral Research Jul 2024Hepatitis E is an underestimated disease, leading to estimated 20 million infections and up to 70,000 deaths annually. Infections are mostly asymptomatic, but can reach...
Hepatitis E is an underestimated disease, leading to estimated 20 million infections and up to 70,000 deaths annually. Infections are mostly asymptomatic, but can reach mortality rates up to 25% in pregnant women or become chronic in immunocompromised patients. Hepatitis E virus (HEV) infection have been associated with a range of extrahepatic manifestations, including a spectrum of neurological symptoms. Current therapy options are limited to non-specific antivirals like ribavirin, but recently, repurposed viral polymerase inhibitors like sofosbuvir and NITD008 were described to inhibit HEV replication. Here, we evaluated the efficacy of these drugs in various neuronal-derived cell lines to determine their potency outside the liver. Our findings indicate that both drugs, especially sofosbuvir, exhibited reduced efficacy in neuronal cells compared to hepatic cells. These results should be taken into account in the development of direct-acting antivirals for HEV and their potency at extrahepatic replication sites.
Topics: Sofosbuvir; Antiviral Agents; Humans; Hepatitis E virus; Virus Replication; Neurons; Cell Line; Hepatitis E; Adenosine
PubMed: 38825018
DOI: 10.1016/j.antiviral.2024.105922 -
Journal of Pharmaceutical and... Sep 2024GS-441524 is an adenosine nucleoside antiviral demonstrating significant efficacy in the treatment of feline infectious peritonitis (FIP), an otherwise fatal illness,...
GS-441524 is an adenosine nucleoside antiviral demonstrating significant efficacy in the treatment of feline infectious peritonitis (FIP), an otherwise fatal illness, resulting from infection with feline coronavirus. However, following the emergence of COVID-19, veterinary development was halted, and Gilead pursued clinical development of a GS-441524 pro-drug, resulting in the approval of Remdesivir under an FDA emergency use authorization. Despite lack of regulatory approval, GS-441524 is available without a prescription through various unlicensed online distributors and is commonly purchased by pet owners for the treatment of FIP. Herein, we report data obtained from the analytical characterization of two feline renal calculi, demonstrating the propensity for GS-441524 to cause renal toxicity through drug-induced crystal nephropathy in vivo. As definitive diagnosis of drug-induced crystal nephropathy requires confirmation of the lithogenic material to accurately attribute a mechanism of toxicity, renal stone composition and crystalline matrix were characterized using ultra-performance liquid chromatography photodiode array detection (UPLC-PDA), ultra-performance liquid chromatography mass spectrometry (LCMS), nuclear magnetic resonance (NMR) spectroscopy, X-ray powder diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). This work serves to provide the first analytical confirmation of GS-441524-induced crystal nephropathy in an effort to support toxicologic identification of adverse renal effects caused by administration of GS-441524 or any pro-drug thereof.
Topics: Animals; Adenosine Monophosphate; Alanine; Antiviral Agents; Cats; Kidney Calculi; COVID-19 Drug Treatment; Adenosine; Cat Diseases; Chromatography, High Pressure Liquid; Magnetic Resonance Spectroscopy
PubMed: 38823223
DOI: 10.1016/j.jpba.2024.116248 -
Iranian Journal of Allergy, Asthma, and... Apr 2024Asthma is a chronic respiratory disease that is characterized by airway inflammation, excessive mucus production, and airway remodeling. Prevention and treatment for...
Asthma is a chronic respiratory disease that is characterized by airway inflammation, excessive mucus production, and airway remodeling. Prevention and treatment for asthma is an urgent issue in clinical studies. In recent years, N6-methyladenosine methylation (m6A) has emerged as a promising regulatory approach involved in multiple diseases. ALKBH5 (alkB homolog 5) is a demethylase widely studied in disease pathologies. This work aimed to explore the regulatory mechanisms underlying the ALKBH5-regulated asthma. We established an interleukin-13 (IL-13)-stimulated cell model to mimic the in vitro inflammatory environment of asthma. ALKBH5 knockdown in bronchial epithelial cells was performed using siRNAs, and the knockdown efficacy was analyzed by quantitative PCR (qPCR). Cell viability and proliferation were measured by cell counting kit 8 (CCK-8) and colony formation assay. The ferroptosis was assessed by measuring the total iron, Fe2+, lipid reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) levels. The enrichment of N6-methyladenosine methylation (m6A) modification was detected by the MeRIP assay. Knockdown of ALKBH5 significantly elevated the survival and colony formation ability of bronchial epithelial cells in the IL-13 induction model. The levels of total iron, Fe2+, lipid ROS, and MDA were remarkedly elevated, and the SOD level was reduced in IL-13-induced bronchial epithelial cells, and depletion of ALKBH5 reversed these effects. Knockdown of ALKBH5 elevated the enrichment of m6A modification and expression of glutathione peroxidase 4 (GPX4). Knockdown of GPX4 abolished the pro-proliferation and anti-ferroptosis effects of siALKBH5. Knockdown of ALKBH5 improved the proliferation of bronchial epithelial cells and alleviated cell ferroptosis.
Topics: AlkB Homolog 5, RNA Demethylase; Asthma; Humans; Adenosine; Cell Proliferation; Methylation; Disease Progression; Cell Line; Ferroptosis; Epithelial Cells; Down-Regulation; Bronchi; Gene Knockdown Techniques; Cell Survival
PubMed: 38822515
DOI: 10.18502/ijaai.v23i2.15326 -
Molecular Cancer May 2024Elevated evidence suggests that the SENPs family plays an important role in tumor progression. However, the role of SENPs in AML remains unclear.
N6-methyladenosine-modified SENP1, identified by IGF2BP3, is a novel molecular marker in acute myeloid leukemia and aggravates progression by activating AKT signal via de-SUMOylating HDAC2.
BACKGROUND
Elevated evidence suggests that the SENPs family plays an important role in tumor progression. However, the role of SENPs in AML remains unclear.
METHODS
We evaluated the expression pattern of SENP1 based on RNA sequencing data obtained from OHSU, TCGA, TARGET, and MILE datasets. Clinical samples were used to verify the expression of SENP1 in the AML cells. Lentiviral vectors shRNA and sgRNA were used to intervene in SENP1 expression in AML cells, and the effects of SENP1 on AML proliferation and anti-apoptosis were detected using in vitro and in vivo models. Chip-qPCR, MERIP-qPCR, CO-IP, RNA pulldown, and dual-luciferase reporter gene assays were used to explore the regulatory mechanisms of SNEP1 in AML.
RESULTS
SENP1 was significantly upregulated in high-risk AML patients and closely related to poor prognosis. The AKT/mTOR signaling pathway is a key downstream pathway that mediates SENP1's regulation of AML proliferation and anti-apoptosis. Mechanistically, the CO-IP assay revealed binding between SENP1 and HDAC2. SUMO and Chip-qPCR assays suggested that SENP1 can desumoylate HDAC2, which enhances EGFR transcription and activates the AKT pathway. In addition, we found that IGF2BP3 expression was upregulated in high-risk AML patients and was positively correlated with SENP1 expression. MERIP-qPCR and RIP-qPCR showed that IGF2BP3 binds SENP1 3-UTR in an m6A manner, enhances SENP1 expression, and promotes AKT pathway conduction.
CONCLUSIONS
Our findings reveal a distinct mechanism of SENP1-mediated HDAC2-AKT activation and establish the critical role of the IGF2BP3/SENP1signaling axis in AML development.
Topics: Animals; Female; Humans; Male; Mice; Adenosine; Apoptosis; Biomarkers, Tumor; Cell Line, Tumor; Cell Proliferation; Cysteine Endopeptidases; Disease Progression; Gene Expression Regulation, Leukemic; Histone Deacetylase 2; Leukemia, Myeloid, Acute; Prognosis; Proto-Oncogene Proteins c-akt; RNA-Binding Proteins; Signal Transduction; Sumoylation; Xenograft Model Antitumor Assays
PubMed: 38822351
DOI: 10.1186/s12943-024-02013-y -
The Lancet. Oncology Jun 2024In the primary analysis report of the GAIA/CLL13 trial, we found that venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib improved undetectable measurable... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
First-line venetoclax combinations versus chemoimmunotherapy in fit patients with chronic lymphocytic leukaemia (GAIA/CLL13): 4-year follow-up from a multicentre, open-label, randomised, phase 3 trial.
BACKGROUND
In the primary analysis report of the GAIA/CLL13 trial, we found that venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib improved undetectable measurable residual disease (MRD) rates and progression-free survival compared with chemoimmunotherapy in patients with previously untreated chronic lymphocytic leukaemia. However, to our knowledge, no data on direct comparisons of different venetoclax-based combinations are available.
METHODS
GAIA/CLL13 is an open-label, randomised, phase 3 study conducted at 159 sites in ten countries in Europe and the Middle East. Eligible patients were aged 18 years or older, with a life expectancy of at least 6 months, an Eastern Cooperative Oncology group performance status of 0-2, a cumulative illness rating scale score of 6 or lower or a single score of 4 or lower, and no TP53 aberrations. Patients were randomly assigned (1:1:1:1), with a computer-generated list stratified by age, Binet stage, and regional study group, to either chemoimmunotherapy, venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. All treatments were administered in 28-day cycles. Patients in the chemoimmunotherapy group received six cycles of treatment, with patients older than 65 years receiving intravenous bendamustine (90 mg/m, days 1-2), whereas patients aged 65 years or younger received intravenous fludarabine (25 mg/m, days 1-3) and intravenous cyclophosphamide (250 mg/m, days 1-3). Intravenous rituximab (375 mg/m, day 1 of cycle 1; 500 mg/m, day 1 of cycles 2-6) was added to chemotherapy. In the experimental groups, patients received daily venetoclax (400 mg orally) for ten cycles after a 5-week ramp-up phase starting on day 22 of cycle 1. In the venetoclax-rituximab group, intravenous rituximab (375 mg/m, day 1 of cycle 1; 500 mg/m, day 1 of cycles 2-6) was added. In the obinutuzumab-containing groups, obinutuzumab was added (cycle 1: 100 mg on day 1, 900 mg on day 2, and 1000 mg on days 8 and 15; cycles 2-6: 1000 mg on day 1). In the venetoclax-obinutuzumab-ibrutinib group, daily ibrutinib (420 mg orally, from day 1 of cycle 1) was added until undetectable MRD was reached in two consecutive measurements (3 months apart) or until cycle 36. The planned treatment duration was six cycles in the chemoimmunotherapy group, 12 cycles in the venetoclax-rituximab and the venetoclax-obinutuzumab group and between 12 and 36 cycles in the venetoclax-obinutuzumab-ibrutinib group. Coprimary endpoints were the undetectable MRD rate in peripheral blood at month 15 for the comparison of venetoclax-obinutuzumab versus standard chemoimmunotherapy and investigator-assessed progression-free survival for the comparison of venetoclax-obinutuzumab-ibrutinib versus standard chemoimmunotherapy, both analysed in the intention-to-treat population (ie, all patients randomly assigned to treatment) with a split α of 0·025 for each coprimary endpoint. Both coprimary endpoints have been reported elsewhere. Here we report a post-hoc exploratory analysis of updated progression-free survival results after a 4-year follow-up of our study population. Safety analyses included all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT02950051, recruitment is complete, and all patients are off study treatment.
FINDINGS
Between Dec 13, 2016, and Oct 13, 2019, 1080 patients were screened and 926 were randomly assigned to treatment (chemoimmunotherapy group n=229; venetoclax-rituximab group n=237; venetoclax-obinutuzumab group n=229; and venetoclax-obinutuzumab-ibrutinib group n=231); mean age 60·8 years (SD 10·2), 259 (28%) of 926 patients were female, and 667 (72%) were male (data on race and ethnicity are not reported). At data cutoff for this exploratory follow-up analysis (Jan 31, 2023; median follow-up 50·7 months [IQR 44·6-57·9]), patients in the venetoclax-obinutuzumab group had significantly longer progression-free survival than those in the chemoimmunotherapy group (hazard ratio [HR] 0·47 [97·5% CI 0·32-0·69], p<0·0001) and the venetoclax-rituximab group (0·57 [0·38-0·84], p=0·0011). The venetoclax-obinutuzumab-ibrutinib group also had a significantly longer progression-free survival than the chemoimmunotherapy group (0·30 [0·19-0·47]; p<0·0001) and the venetoclax-rituximab group (0·38 [0·24-0·59]; p<0·0001). There was no difference in progression-free survival between the venetoclax-obinutuzumab-ibrutinib and venetoclax-obinutuzumab groups (0·63 [0·39-1·02]; p=0·031), and the proportional hazards assumption was not met for the comparison between the venetoclax-rituximab group versus the chemoimmunotherapy group (log-rank p=0·10). The estimated 4-year progression-free survival rate was 85·5% (97·5% CI 79·9-91·1; 37 [16%] events) in the venetoclax-obinutuzumab-ibrutinib group, 81·8% (75·8-87·8; 55 [24%] events) in the venetoclax-obinutuzumab group, 70·1% (63·0-77·3; 84 [35%] events) in the venetoclax-rituximab group, and 62·0% (54·4-69·7; 90 [39%] events) in the chemoimmunotherapy group. The most common grade 3 or worse treatment-related adverse event was neutropenia (114 [53%] of 216 patients in the chemoimmunotherapy group, 109 [46%] of 237 in the venetoclax-rituximab group, 127 [56%] of 228 in the venetoclax-obinutuzumab group, and 112 [48%] of 231 in the venetoclax-obinutuzumab-ibrutinib group). Deaths determined to be associated with study treatment by the investigator occurred in three (1%) patients in the chemoimmunotherapy group (n=1 due to each of sepsis, metastatic squamous cell carcinoma, and Richter's syndrome), none in the venetoclax-rituximab and venetoclax-obinutuzumab groups, and four (2%) in the venetoclax-obinutuzumab-ibrutinib group (n=1 due to each of acute myeloid leukaemia, fungal encephalitis, small-cell lung cancer, and toxic leukoencephalopathy).
INTERPRETATION
With more than 4 years of follow-up, venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib significantly extended progression-free survival compared with both chemoimmunotherapy and venetoclax-rituximab in previously untreated, fit patients with chronic lymphocytic leukaemia, thereby supporting their use and further evaluation in this patient group, while still considering the higher toxicities observed with the triple combination.
FUNDING
AbbVie, Janssen, and F Hoffmann-La Roche.
Topics: Humans; Bridged Bicyclo Compounds, Heterocyclic; Sulfonamides; Antineoplastic Combined Chemotherapy Protocols; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Female; Aged; Middle Aged; Follow-Up Studies; Piperidines; Vidarabine; Rituximab; Adenine; Antibodies, Monoclonal, Humanized; Progression-Free Survival; Cyclophosphamide; Pyrazoles; Pyrimidines; Immunotherapy; Adult
PubMed: 38821083
DOI: 10.1016/S1470-2045(24)00196-7 -
International Journal of Medical... 2024This study aims to explore the molecular mechanisms and associated pathways of myocardial infarction (MI). We employed a variety of analytical methods, including...
This study aims to explore the molecular mechanisms and associated pathways of myocardial infarction (MI). We employed a variety of analytical methods, including Mendelian Randomization (MR) analysis, transcriptome microarray data analysis, gene function and pathway enrichment analysis, untargeted metabolomic mass spectrometry analysis, and gene-metabolite interaction network analysis. The MR analysis results revealed a significant impact of mitochondrial DNA copy number on MI and coronary artery bypass grafting. Transcriptome analysis unveiled numerous differentially expressed genes associated with myocardial ischemia, with enrichment observed in cardiac function and energy metabolism pathways. Metabolomic analysis indicated a significant downregulation of mitochondrial regulation pathways in ischemic myocardium. T500 metabolite quantification analysis identified 90 differential metabolites between MI and Sham groups, emphasizing changes in metabolites associated with energy metabolism. Gene-metabolite interaction network analysis revealed the significant roles of key regulatory molecules such as HIF1A, adenosine, TBK1, ATP, NRAS, and EIF2AK3, in the pathogenesis of myocardial ischemia. In summary, this study provides important insights into the molecular mechanisms of MI and highlights interactions at multiple molecular levels, contributing to the establishment of new theoretical foundations for the diagnosis and treatment of MI.
Topics: Myocardial Infarction; Humans; Adenosine; Energy Metabolism; Gene Regulatory Networks; Gene Expression Profiling; Mendelian Randomization Analysis; DNA, Mitochondrial; Mitochondria; Metabolomics; Transcriptome
PubMed: 38818463
DOI: 10.7150/ijms.97066 -
Scientific Reports May 2024Pulmonary arterial hypertension (PAH) is a fatal disease featured by high morbidity and mortality. Although Cordycepin is known for its anti-inflammatory, antioxidant...
Pulmonary arterial hypertension (PAH) is a fatal disease featured by high morbidity and mortality. Although Cordycepin is known for its anti-inflammatory, antioxidant and immune-enhancing effects, its role in PAH treatment and the underlying mechanisms remain unclear. The therapeutic effects of Cordycepin on rats with PAH were investigated using a monocrotaline (MCT)-induced rat model. The metabolic effects of Cordycepin were assessed based on the plasma metabolome. The potential mechanisms of Cordycepin in PAH treatment were investigated through transcriptome sequencing and validated in pulmonary artery smooth muscle cells (PASMC). Evaluations included hematoxylin and eosin staining for pulmonary vascular remodeling, CCK-8 assay, EDU, and TUNEL kits for cell viability, proliferation, and apoptosis, respectively, and western blot for protein expression. Cordycepin significantly reduced right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) in PAH rats, and mitigated pulmonary vascular remodeling. Plasma metabolomics showed that Cordycepin could reverse the metabolic disorders in the lungs of MCT-induced PAH rats, particularly impacting linoleic acid and alpha-linolenic acid metabolism pathways. Transcriptomics revealed that the P53 pathway might be the primary pathway involved, and western blot results showed that Cordycepin significantly increased P53 and P21 protein levels in lung tissues. Integrated analysis of transcriptomics and metabolomics suggested that these pathways were mainly enriched in linoleic acid metabolism and alpha-linolenic acid metabolism pathway. In vitro experiments demonstrated that Cordycepin significantly inhibited the PDGFBB (PD)-induced abnormal proliferation and migration of PASMC and promoted PD-induced apoptosis. Meanwhile, Cordycepin enhanced the expression levels of P53 and P21 proteins in PD-insulted PASMC. However, inhibitors of P53 and P21 eliminated these effects of Cordycepin. Cordycepin may activate the P53-P21 pathway to inhibit abnormal proliferation and migration of PASMC and promote apoptosis, offering a potential approach for PAH treatment.
Topics: Animals; Deoxyadenosines; Rats; Male; Apoptosis; Pulmonary Arterial Hypertension; Cell Proliferation; Transcriptome; Metabolomics; Myocytes, Smooth Muscle; Monocrotaline; Pulmonary Artery; Rats, Sprague-Dawley; Disease Models, Animal; Vascular Remodeling; Tumor Suppressor Protein p53; Linoleic Acid; Hypertrophy, Right Ventricular; Gene Expression Profiling
PubMed: 38816406
DOI: 10.1038/s41598-024-62163-3 -
Turkish Journal of Medical Sciences 2023Temporomandibular Disorders (TMD), as in the occurrence of many diseases, have been associated with oxidative stress (OS) resulting from the disruption of antioxidant...
BACKGROUND/AIM
Temporomandibular Disorders (TMD), as in the occurrence of many diseases, have been associated with oxidative stress (OS) resulting from the disruption of antioxidant mechanisms and the accumulation of reactive oxygen species in tissues. This study was designed to compare salivary and serum OS and inflammation markers of individuals with TMD and healthy subjects.
MATERIALS AND METHODS
A prospective cross-sectional study was conducted. Twenty-seven TMD patients diagnosed with disc displacement (DD) according to Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and 17 healthy subjects were enrolled in the study. Prior to any treatment, serum, and saliva samples were taken from the patients and centrifuged, and stored at -80 °C until analyzed. All samples were examined for Interleukin-6 (IL-6), Malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) concentrations.
RESULTS
There was no significant difference between the groups regarding median values of 8-OHdG, IL-6, and MDA (p > 0.05). When the relationship between serum and salivary 8-OHdG, IL-6, and MDA levels in all subjects was evaluated, there was a strong positive correlation between the levels of 8-OHdG and IL-6 in the serum (r = 0.752, p <0.001). In the study group, when the relationship between pain levels and serum and saliva 8-OHdG, IL-6, and MDA levels was assessed, a positive and strong correlation was found between the levels of 8-OHdG and IL-6 in serum.
CONCLUSION
Although the strong correlation between pain scores and serum 8-OHdG and MDA levels supports the hypothesis that inflammation and OS mechanisms may be interrelated, according to the results of the study, inflammatory and OS markers in patients with TMD were not different from healthy individuals.
Topics: Humans; Oxidative Stress; Saliva; Temporomandibular Joint Disorders; Female; Adult; Male; Cross-Sectional Studies; Biomarkers; Interleukin-6; Prospective Studies; Malondialdehyde; Inflammation; 8-Hydroxy-2'-Deoxyguanosine; Young Adult; Middle Aged
PubMed: 38813510
DOI: 10.55730/1300-0144.5737 -
Turkish Journal of Medical Sciences 2023Titanium dioxide nanoparticles are widely used in a variety of products, including sunscreens, paints, and ceramics. However, their increasing use has raised concerns...
BACKGROUND/AIM
Titanium dioxide nanoparticles are widely used in a variety of products, including sunscreens, paints, and ceramics. However, their increasing use has raised concerns about their potential health risks. Titanium dioxide nanoparticles have been shown to have the ability to enter the bloodstream and accumulate in various tissues, reaching the fetus via the placenta. The aim of this study was to investigate the cytotoxic effects of titanium dioxide nanoparticles on a human embryonic lung cell line (HEL 299/An1) and the formation of oxidative DNA damage.
MATERIALS AND METHODS
The cytotoxic effects of brookite-based titanium dioxide nanoparticles (<100 nm) were assessed using the 3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay for 24 and 48 h. Cell titanium levels were determined using inductively coupled plasma mass spectrometry. Oxidative DNA damage was assessed by measuring the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) as a biomarker.
RESULTS
Titanium dioxide nanoparticles caused dose-dependent cytotoxicity in HEL 299/An1 cells. The IC values were 25.93 μM and 0.054 μM after 24 h and 48 h of exposure, respectively. Cell titanium levels were found to be 25,967 ppb after 24 h and 210,353 ppb after 48 h (p < 0.01). 8-OHdG was detected at 32.96 ng/mL after 24 h of exposure and 17.89 ng/mL after 48 h of exposure.
CONCLUSION
In our study, it was shown that titanium nanoparticles caused dose-dependent cytotoxicity and oxidative DNA damage in human embryonic lung cells. The nanoparticles also accumulated in cells and were taken up in higher amounts after 48 h of exposure. These findings suggest that titanium dioxide nanoparticles may pose a health risk, especially for pregnant women who may not be aware of their pregnancy. Therefore, it is important to take preventive measures to reduce exposure to these nanoparticles.
Topics: Titanium; Humans; DNA Damage; Cell Line; Lung; Oxidative Stress; Nanoparticles; 8-Hydroxy-2'-Deoxyguanosine; Cell Survival; Metal Nanoparticles
PubMed: 38813501
DOI: 10.55730/1300-0144.5733