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1.
Cytogenet Genome Res ; 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37906989

RESUMO

BACKGROUND: Development of resistance upon exposure to small doses of ionizing radiation followed by higher doses is known as radiation-induced adaptive response (RIAR). Traditionally, the induction of the RIAR phenomenon at the cellular level has been examined in cell lines, animal models, and epidemiological studies where people live in high natural background radiation. SUMMARY: The primary intention of the earlier studies was to corroborate the existence of RIAR and the mechanism involved in mediating the response surveyed by exposure to a low dose of radiation (<500 mGy) as priming dose towards the radiation protection point of view. However, the investigation has shifted the focus to understand the relevance of this phenomenon at clinically relevant set-ups (high doses in the order of Gy) and can be exploited during radiotherapy as RIAR is considered a mechanism for the development of radioresistance. Although the knowledge of molecular mechanisms at the cellular level has evolved significantly in multi-fractionated radiotherapy regimes, its relevance in developing radioresistance at low doses remains elusive. The authors recapitulate the existing knowledge on RIAR at cellular levels, specifically after low-dose exposure as an adaptive dose, and discussed its potential implications in clinical radiotherapy outcomes. KEY MESSAGES: Recent studies contributed to understand the signaling molecules, pathways, and inhibitors to mitigate RIAR-mediated radiation resistance and persistent radio-tolerance at the cellular level. Monitoring the disease progression in tumor samples or liquid biopsies before, during, and after therapy with suitable biomarkers has been proposed as a strategy to translate the phenomena into clinical scenario.

2.
Cytogenet Genome Res ; 163(3-4): 210-222, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37253332

RESUMO

Quantification of gene expression signatures has been substantiated as a potential and rapid marker for radiation triage and biodosimetry during nuclear emergencies. Similar to the established biodosimetry assays, the gene expression assay has drawbacks such as being highly dynamic and transient, not specific to ionizing radiation, and also influenced by confounding factors such as gender, health status, lifestyle, and inflammation. In view of that, prior knowledge of baseline expression of certain candidate genes in a population could complement the discrimination of the unexposed from the exposed individuals without the need for individual pre-exposure controls. We intended to establish a baseline expression of reported radiation-responsive genes such as CDKN1A, DDB2, FDXR, and PCNA in the blood samples of healthy human participants and then compare it with diabetic/hypertension participants (as a chronic inflammatory condition) drawn from south Indian population. Further, we have examined the appropriateness of the assay for radiation triage-like situations; i.e., the expression profiles of those genes were examined in the participants who underwent X-ray-based medical imaging. Acute inflammation induced by lipopolysaccharide exposure in the blood significantly increased the fold expression of those genes (p < 0.0001) compared to the control. Whereas the basal expression level of those genes among the participants with the inflammatory condition is marginally higher than those observed in the healthy participants; despite the excess, the fold increase in those genes between the groups did not differ significantly. Consistent with the inflammatory participants, the basal expression level of those genes in the blood sample of participants who received X-radiation during neuro-interventional and computed tomography imaging is marginally higher than those observed in the pre-exposure of respective groups. Nevertheless, the fold increase in those genes did not differ significantly as the fold change fell within the two folds. Thus, overall results suggest that the utility of CDKN1A, DDB2, FDXR, and PCNA gene expression for radiation triage specific after very low-dose radiation exposure needs to be interpreted with caution for a much more reliable triage.


Assuntos
Povo Asiático , Triagem , Humanos , Antígeno Nuclear de Célula em Proliferação , Inflamação , Expressão Gênica
3.
Mol Biol Rep ; 50(5): 4239-4252, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36905404

RESUMO

BACKGROUND: Endometriosis is a complex gynaecological disorder that contributes to infertility, dysmenorrhea, dyspareunia, and other chronic issues. It is a multifactorial disease involving genetic, hormonal, immunological and environmental components. Endometriosis's pathogenesis remains unclear. AIM OF THE STUDY: was to analyse the polymorphisms in Interleukin 4, Interleukin 18, FCRL3 and sPLA2IIa genes to identify any significant association with the risk of endometriosis. MATERIAL AND METHODS: This study evaluated the polymorphism of -590 C/T in interleukin- 4(IL-4) gene, C607A in Interleukin - 18(IL-18) gene, -169T > C in FCRL3 gene and 763 C > G in sPLA2IIa gene in women with endometriosis. The case-control study included 150 women with endometriosis and 150 apparently healthy women as control subjects. DNA was extracted from peripheral blood leukocytes and endometriotic tissue of cases and blood samples for controls and further analysed by PCR amplification and then sequencing was carried out to find the allele and genotypes of the subjects and then to analyse the relationship between the gene polymorphisms and endometriosis. To evaluate the association of the different genotypes, 95% confidence intervals (CI) were calculated. RESULTS: Interleukin - 18 and FCRL3 gene polymorphisms of endometriotic tissue and blood samples of endometriosis (cases) showed significantly associated (OR = 4.88 [95% CI = 2.31-10.30], P > 0.0001) and (OR = 4.00 [95% CI = 2.2-7.33], P > 0.0001) when compared with normal blood samples. However, there was no significant difference in Interleukin - 4 and sPLA2IIa gene polymorphisms between control women and patients with endometriosis. CONCLUSIONS: The present study suggests that the IL-18 and FCRL3 gene polymorphisms are associated with a higher risk for endometriosis, which delivers valuable knowledge of endometriosis's pathogenesis. However, a larger sample size of patients from various ethnic backgrounds is necessary to evaluate whether these alleles have a direct effect on disease susceptibility.


Assuntos
Endometriose , Interleucina-18 , Interleucina-4 , Receptores Imunológicos , Feminino , Humanos , Estudos de Casos e Controles , Endometriose/genética , Frequência do Gene/genética , Predisposição Genética para Doença , Genótipo , Interleucina-18/genética , Interleucina-4/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores Imunológicos/genética
4.
J Cell Biochem ; 120(4): 5722-5728, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30320915

RESUMO

In vitro human lymphocyte culture methodology is well established yet certain confounding factors such as age, medical history as well as individual's blood type may potentially modulate in vitro proliferation response. These factors have to be carefully evaluated to release reliable test report in routine cytogenetic evaluation for various genetic conditions, radiation biodosimetry, etc. With this objective, the current study was focused on analyzing the proliferation response of lymphocytes drawn from 90 individuals (21-29 years) with different blood types. The proliferation response was assessed in the cultured lymphocytes by cell cycle, mitotic index (MI), and nuclear division index (NDI) after stimulation with phytohaemagglutinin (PHA). To investigate the toxic effect on proliferation, MI was calculated in representative samples of each blood type were X-irradiated. The results showed that there was no significant difference among the cell cycle phases of lymphocytes in different blood types (P > 0.05). Similarly, both MI and NDI of lymphocytes derived from different blood types also did not show significant difference ( P > 0.05). The extensive interindividual variation within and among the blood types is likely responsible for the lack of significant difference in lymphocyte proliferation. Although spontaneous proliferation efficiency of lymphocytes of different blood types after PHA stimulation was grossly similar, the MI observed after radiation exposure showed a significant difference ( P < 0.05) indicating a differential proliferation response among the blood types. Our results suggest that the blood types did not have any impact on PHA-induced proliferation; however, a specific differential lymphocyte proliferation observed after radiation exposure needs to be considered.


Assuntos
Antígenos de Grupos Sanguíneos/classificação , Antígenos de Grupos Sanguíneos/metabolismo , Divisão do Núcleo Celular , Proliferação de Células , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/citologia , Mitose , Adulto , Ciclo Celular , Células Cultivadas , Feminino , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Masculino , Fito-Hemaglutininas/farmacologia , Adulto Jovem
5.
Clin Exp Nephrol ; 21(1): 127-133, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26820844

RESUMO

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is found in 10-20 % of children with idiopathic nephrotic syndrome (INS). In SRNS patients, common histopathological subtypes are Focal segmental glomerulosclerosis (FSGS) (53 %) and minimal change disease (MCD) (27 %). Familial forms of FSGS constitute podocyte diseases with varying severity and age of onset. Podocin gene (NPHS2) mutations cause childhood-onset steroid-resistant FSGS and MCD to adult-onset FSGS. In view of genetic variations and susceptibility to the disease, the present investigation was undertaken to study the pattern of genetic mutation in children from South India. METHODS: Mutation analysis was carried out by direct sequencing of the entire NPHS2 gene (eight exons) using specific primers in 200 INS (100 SRNS and 100 steroid sensitive) children and 100 healthy controls. The allele and genotype frequencies of NPHS2 gene were calculated for both cases and controls as per Hardy-Weinberg equilibrium. RESULTS: Among the SRNS patients, 18 % revealed both heterozygous and homozygous mutations. Out of 12 mutations, 8 were homozygous and 4 were heterozygous. Interestingly, we found two novel SNPs in exon 4 of NPHS2 gene, which are documented and submitted to dbsnp database (Ref rs12401711 and rs12401708). CONCLUSION: Mutational analysis of NPHS2 would be advisable at the start of treatment. The genetic variations detected in the study would serve as the important molecular marker in treating the children's at early stage, which also enables to detect carriers, prenatal diagnosis and provide genetic counseling to couples at risk.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Mutação , Síndrome Nefrótica/congênito , Polimorfismo de Nucleotídeo Único , Adolescente , Idade de Início , Estudos de Casos e Controles , Criança , Pré-Escolar , Análise Mutacional de DNA , Éxons , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Testes Genéticos/métodos , Heterozigoto , Homozigoto , Humanos , Índia , Lactente , Masculino , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/genética , Fenótipo , Prognóstico
6.
Pediatr Cardiol ; 36(7): 1470-5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25981563

RESUMO

Conotruncal heart defects (CTHDS) are a subgroup of congenital heart malformations that are considered to be a folate-sensitive birth defect. It has been hypothesized that polymorphisms in genes that code for key enzymes in the folate pathway may alter enzyme activity, leading to disruptions in folate metabolism and thus may influence the risk of such heart defects. This study was designed to investigate the association of six selected folate-metabolizing gene polymorphisms with the risk of non-syndromic CTHDs in an Indian population. This was a case-control study involving 96 cases of CTHDs and 100 control samples, ranging in age from birth to 18 years. Genotyping using Sanger sequencing was performed for six single nucleotide polymorphisms of genes involved in folate metabolism. Logistic regression analyses revealed that for the 5,10-methylenetetrahydrofolate (MTHFR) A1298C polymorphism, the CC variant homozygote genotype was associated with a significantly increased risk of CTHDs. The results of this study support an association between the inherited MTHFR A1298C genotype and the risk of CTHDs in an Indian population.


Assuntos
Cardiopatias Congênitas/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Adolescente , Povo Asiático , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Humanos , Índia , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Risco
7.
Food Chem ; 457: 140107, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39032479

RESUMO

Bacillus stercoris PSSR12 (B. stercoris PE), an isolate from rice field soils, was identified via 16s rRNA sequencing. The synthesis of the inulin and inulin producing enzyme (IPE) in B. stercoris PE was verified using SDS-PAGE and FTIR. This study aimed to assess the impact of B. stercoris PE treatment on in vitro inhibition of α-amylase and α-glucosidase from traditional and commercial rice varieties of South India. Additionally, the study investigated enzymatic inhibition and mRNA expression of starch synthesis genes (RAmy1a, GBSSIa, SBEIIa, and SBEIIb). Glucose transporter gene expression (GLUT1 and GLUT4) patterns were analyzed in 3T3-L1 adipocytes to evaluate glucose uptake in B. stercoris PE treated rice varieties. The application of B. stercoris PE enhanced grain quality by imparting starch ultra-structural rigidity, inhibiting starch metabolizing enzymes, and inducing molecular changes in starch synthesis genes. This approach holds promise for managing type II diabetes mellitus and potentially reducing insulin dependence.


Assuntos
Glucose , Inulina , Oryza , Amido , alfa-Amilases , Oryza/metabolismo , Oryza/química , Oryza/microbiologia , Inulina/metabolismo , Inulina/química , Glucose/metabolismo , Amido/metabolismo , Amido/química , alfa-Amilases/metabolismo , alfa-Amilases/genética , Bacillus/metabolismo , Bacillus/genética , Bacillus/química , Camundongos , alfa-Glucosidases/metabolismo , alfa-Glucosidases/genética , Animais
8.
Nucl Med Mol Imaging ; 58(6): 341-353, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39308490

RESUMO

Purpose: Ionizing radiation-based technologies are extensively used in the diagnosis and treatment of diseases. While utilizing the technologies, exposure to a certain amount of radiation is unavoidable. Data can be obtained from participants who received radiation during medical imaging and therapeutic purposes to predict the effects of low-dose radiation. Methods: To understand the effects of low-dose radiation, participants (n = 22) who received radioactive I-131 for scan/therapy were used as a model in this study. Blood samples were drawn pre- and post-administration of I-131. Biological effects were measured using markers of DNA damage (γ-H2AX, micronucleus (MN), and chromosomal aberrations (CA)) and response to damage through gene expression changes (ATM, CDKN1A, DDB2, FDXR, and PCNA) in blood samples. Results: Mean frequency of γ-H2AX foci in pre-samples was 0.28 ± 0.16, and post-samples were 1.03 ± 0.60. γ-H2AX foci frequency obtained from post-samples showed significant (p < 0.0001) and a heterogeneous increase in all the participants (received I-131 for scan/therapy) when compared to pre-samples. A significant increase (p < 0.0001) in MN and CA frequency was also observed in participants who received the I-131 therapy. Gene expression analysis indicates that all genes (ATM, CDKN1A, DDB2, FDXR, and PCNA) were altered in post-samples, although with varying degrees, suggesting that the cellular responses to DNA damage, such as damage repair, cell cycle regulation to aid in repair and apoptosis are increased, which priority is given to repair, followed by apoptosis. Conclusion: The results of this study indicate that the participants who received I-131 (low doses of ß- and γ-radiation) can produce substantial biological effects.

9.
Int J Biol Macromol ; 273(Pt 1): 132954, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38852726

RESUMO

This study explores the potential of liposome encapsulated silica immobilized cytochrome P450 monooxygenase (LSICY) for bioremediation of mercury (Hg2+). Current limitations in Hg2+ reduction, including sensitivity to factors like pH and cost, necessitate alternative methods. We propose LSICY as a solution, leveraging the enzymatic activities of cytochrome P450 monooxygenase (CYPM) for Hg2+ reduction through hydroxylation and oxygenation. Our investigation employs LSICY to assess its efficacy in mitigating Hg2+ toxicity in Oryza sativa (rice) plants. Gas chromatography confirmed gibberellic acid (GA) presence in the Hg2+ reducing bacteria Priestia megaterium RP1 (PMRP1), highlighting a potential link between CYP450 activity and plant health. This study demonstrates the promise of LSICY as a sustainable and effective approach for Hg2+ bioremediation, promoting a safer soil environment.


Assuntos
Biodegradação Ambiental , Sistema Enzimático do Citocromo P-450 , Giberelinas , Lipossomos , Mercúrio , Oryza , Sistema Enzimático do Citocromo P-450/metabolismo , Giberelinas/metabolismo , Giberelinas/farmacologia
11.
World J Radiol ; 14(7): 219-228, 2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-36160628

RESUMO

Coronaviruses are a diverse group of viruses that infect both animals and humans. Even though the existence of coronavirus and its infection to humans is not new, the 2019-novel coronavirus (nCoV) caused a major burden to individuals and society i.e., anxiety, fear of infection, extreme competition for hospitalization, and more importantly financial liability. The nCoV infection/disease diagnosis was based on non-specific signs and symptoms, biochemical parameters, detection of the virus using reverse-transcription polymerase chain reaction (RT-PCR), and X-ray-based imaging. This review focuses on the consolidation of potentials of X-ray-based imaging modality [chest-X radiography (CXR) and chest computed tomography (CT)] and low-dose radiation therapy (LDRT) for screening, severity, and management of COVID-19 disease. Reported studies suggest that CXR contributed significantly toward initial rapid screening/diagnosis and CT- imaging to monitor the disease severity. The chest CT has high sensitivity up to 98% and low specificity for diagnosis and severity of COVID-19 disease compared to RT-PCR. Similarly, LDRT compliments drug therapy in the early recovery/Less hospital stays by maintaining the physiological parameters better than the drug therapy alone. All the results undoubtedly demonstrated the evidence that X-ray-based technology continues to evolve and play a significant role in human health care even during the pandemic.

12.
Artigo em Inglês | MEDLINE | ID: mdl-36462795

RESUMO

Redox modulated pathways play important roles in out-of-field effects of ionizing radiation. We investigated how the redox environment impacts the magnitude of propagation of stressful effects from irradiated to bystander cells. Normal human fibroblasts that have incorporated [3H]-thymidine were intimately co-cultured with bystander cells in a strategy that allowed isolation of bystander cells with high purity. The antioxidant glutathione peroxidase (GPX) was maintained either at wild-type conditions or overexpressed in the bystanders. Following 24 h of coculture, levels of stress-responsive p21Waf1, p-Hdm2, and connexin43 proteins were increased in bystander cells expressing wild-type GPX relative to respective controls. These levels were significantly attenuated when GPX was ectopically overexpressed, demonstrating by direct approach the involvement of a regulator of intracellular redox homeostasis. Evidence of participation of pro-oxidant compounds was generated by exposing confluent cell cultures to low fluences of 3.7 MeV α particles in presence or absence of t-butyl hydroperoxide. By 3 h post-exposure to fluences wherein only ∼2% of cells are traversed through the nucleus by a particle track, increases in chromosomal damage were greater than expected in absence of the drug (p < 0.001) and further enhanced in its presence (p < 0.05). While maintenance and irradiation of cell cultures at low oxygen pressure (pO2 3.8 mm Hg) to mimic in vivo still supported the participation of bystander cells in responses assessed by chromosomal damage and stress-responsive protein levels (p < 0.001), the effects were attenuated compared to ambient pO2 (155 mm Hg) (p < 0.05). Together, the results show that bystander effects are attenuated at below ambient pO2 and when metabolic oxidative stress is reduced but increased when the basal redox environment tilts towards oxidizing conditions. They are consistent with bystander effects being independent of radiation dose rate.


Assuntos
Efeito Espectador , Fibroblastos , Oxirredução , Estresse Oxidativo , Oxigênio , Exposição à Radiação , Humanos , Efeito Espectador/efeitos da radiação , Glutationa Peroxidase/metabolismo , Oxirredução/efeitos da radiação , Estresse Oxidativo/efeitos da radiação , Pressão Parcial , Exposição à Radiação/efeitos adversos , Oxigênio/efeitos adversos , Oxigênio/análise , Técnicas de Cocultura , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/efeitos da radiação
13.
Mutat Res Rev Mutat Res ; 787: 108350, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34083048

RESUMO

Radiation triage and biological dosimetry are two initial steps in the medical management of exposed individuals following radiological accidents. Well established biodosimetry methods such as the dicentric (DC) assay, micronucleus (MN) assay, and fluorescence in-situ hybridization (FISH) translocation assay (for residual damage) have been used for this purpose for several decades. Recent advances in scoring methodology and networking among established laboratories have increased triage capacity; however, these methods still have limitations in analysing large sample numbers, particularly because of the ∼ 48 h minimum culture time required prior to analysis. Hence, there is a need for simple, and high throughput markers to identify exposed individuals in case of radiological/nuclear emergencies. In recent years, a few markers were identified, one being phosphorylated histone 2AX (γ-H2AX), which measured a nuclear foci or nuclear staining intensity that was found to be suitable for triage. Measurement of γ-H2AX foci formed at and around the sites of DNA double-strand breaks is a rapid and sensitive biodosimetry method which does not require culturing and is thus promising for the analysis of a large number of samples. In this review, we have summarized the recent developments of γ-H2AX assay in radiation triage and biodosimetry, focusing chiefly on: i) the importance of baseline frequency and reported values among different laboratories, ii) the influence of known and unknown variables on dose estimation, iii) quality assurance such as inter-laboratory comparison between scorers and scoring methods, and iv) current limitations and potential for future development.


Assuntos
Histonas/metabolismo , Triagem/métodos , Biodiversidade , Relação Dose-Resposta à Radiação , Histonas/genética , Humanos , Testes para Micronúcleos/métodos , Radiação Ionizante , Radiometria
14.
Environ Sci Pollut Res Int ; 28(30): 41207-41223, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33782825

RESUMO

This study demonstrates a simple protocol for phytofabrication of titanium dioxide nanoparticles (TiO2NPs) wrapped with bioactive molecules from Ludwigia octovalvis leaf extract and their characterization by UV-visible absorption spectroscopy, Fourier transform spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), X-ray photoelectron spectrum (XPS), and diffuse reflectance spectrum (DRS). The bandgap energy of pure green engineered TiO2 nanoparticles was determined by DRS analysis. The XPS analysis confirmed the purity of the TiO2 nanoparticles. Results show that the synthesized TiO2NPs were spherical in shape with the size ranged from 36 to 81 nm. The green engineered titanium oxide nanocatalyst exhibited enhanced rate of photocatalytic degradation of important textile toxic dyes namely crystal violet (93.1%), followed by methylene blue (90.6%), methyl orange (76.7%), and alizarin red (72.4%) after 6-h exposure under sunlight irradiation. Besides, this study determines the antimicrobial efficiency of TiO2NPs (25 µl and 50 µl), leaf extract (25 µl), and antibiotic (25 µl) against clinically isolated human pathogenic bacterial strains namely Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus vulgaris, Staphylococcus epidermidis, and Escherichia coli. Results show that maximum antibacterial activity with nanotitania treatment noticed was 21.6 and 18.3-mm inhibition in case of S. epidermis and P. aeruginosa, respectively. Enhanced rate of antibiofilm activity towards S. aureus and K. pneumoniae was also observed with TiO2NPs exposure. The biomolecule loaded TiO2NPs exhibited the fastest bacterial deactivation dynamics towards gram-negative bacteria (E. coli), with a complete bacterial inactivation within 105-min exposure. Interestingly, anticancer activity result indicates that percentage of human cervical carcinoma cell (HeLa) viability was negatively correlated with TiO2NPs doses used. The AO/EtBr fluorescent staining result exhibited the occurrence of more apoptosis (dead cells) of HeLa cells due to the exposure of TiO2NPs. Altogether, the present study clearly showed that biomolecules wrapped nanotitania could be used as effective and promising compound for enhanced photocatalytic and biomedical applications in the future.


Assuntos
Nanopartículas Metálicas , Staphylococcus aureus , Antibacterianos/farmacologia , Escherichia coli , Células HeLa , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier , Titânio , Difração de Raios X
15.
Artigo em Inglês | MEDLINE | ID: mdl-34583824

RESUMO

Even though the medical uses of ionizing radiation are well-acknowledged globally as vital tools for the improvement of human health, they also symbolize the major man-made sources of radiation exposure to the population. Estimation of absorbed dose and biological changes after radiation-based imaging might help to better understand the effects of low dose radiation. Because of this, we measured the Entrance Surface Dose (ESD) at different anatomical locations using Lithium tetraborate doped with manganese (Li2B4O7: Mn), recorded Dose Length Product (DLP) and Dose Area Product (DAP), analyzed Chromosomal Aberration (CA), Micronucleus (MN), gamma-H2AX (γ-H2AX), and p53ser15 proteins in the blood lymphocytes of patients (n = 267) underwent Computed Tomography (CT), Positron Emission Tomography-CT (PET/CT), and interventional procedures and healthy volunteers (n = 19). The DLP and effective doses obtained from PET/CT procedures were significantly higher (p < 0.05) when compared to CT. Fluoroscopic time and DAP were significantly higher (p < 0.05) in therapeutic compared to diagnostic interventional procedures. All the anatomical locations registered a significant amount of ESD, the ESD obtained from CT and interventional procedures were significantly (p < 0.05) higher when compared to PET/CT. Fluoroscopic time did not correlate with the ESD (eye, head, thyroid, and shoulder; R2 = 0.03). CA frequency after PET/CT was significantly higher (p < 0.001) when compared to CT and interventional procedures. MN frequency was significantly higher in 24-hs (p < 0.001) post-interventional procedure compared to 2-hs. The mean ± SD of mean fluorescence intensity of γ-H2AX and p53ser15 obtained from all subjects underwent PET/CT and interventional procedures did not show a significant difference (p > 0.05) between pre- and post-procedure. However, the relative fluorescence intensity of γ-H2AX and p53ser15 was >1 in 58.5 % and 65.8 % of subjects respectively. Large inter-individual variation and lack of correlation between physical dose and biomarkers suggest the need for robust dosimetry with a large sample size to understand the health effects of low dose radiation.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Estudos de Casos e Controles , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Artigo em Inglês | MEDLINE | ID: mdl-32928370

RESUMO

Radiation has widespread applications in medicine. However, despite the benefits of medical radiation exposures, adverse long-term health effects are cause for concern. Protein and gene biomarkers are early indicators of cellular response after low-dose exposure. We examined DNA damage by quantifying γ-H2AX foci and expression of twelve candidate genes in the blood lymphocytes of patients exposed to low doses of X-radiation during neuro-interventional procedures. Entrance surface dose (ESD; 10.92-1062.55 mGy) was measured by thermoluminescence dosimetry (TLD). Absorbed dose was estimated using γ-H2AX focus frequency and gene expression, with in vitro dose-response curves generated for the same biomarkers. γ-H2AX foci in post-exposure samples were significantly higher than in pre-exposure samples. Among the genes analysed, FDXR, ATM, BCL2, MDM2, TNFSF9, and PCNA showed increased expression; CDKN1A, DDB2, SESN1, BAX, and TNFRSF10B showed unchanged or decreased expression. Absorbed dose, estimated based on γ-H2AX focus frequency and gene expression changes, did not show any correlation with measured ESD. Patients undergoing interventional procedures receive considerable radiation doses, resulting in DNA damage and altered gene expression. Medical procedures should be carried out using the lowest radiation doses possible without compromising treatment.


Assuntos
Histonas/efeitos da radiação , Linfócitos/efeitos da radiação , Imagem por Ressonância Magnética Intervencionista/efeitos adversos , Exposição à Radiação/efeitos adversos , Dano ao DNA/efeitos da radiação , Relação Dose-Resposta à Radiação , Feminino , Regulação da Expressão Gênica/efeitos da radiação , Histonas/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes , Doses de Radiação , Raios X/efeitos adversos
17.
Artigo em Inglês | MEDLINE | ID: mdl-31326035

RESUMO

Interventional radiology-based imaging is the preferred choice for diagnosis and therapy of many complex diseases, despite possible adverse effects of the radiation exposures. We have measured induced DNA damage and changes in gene expression in relation to entrance surface dose (ESD) in peripheral blood samples of patients (n = 51) who underwent neuro-interventional radiological procedures. The ESD values, measured by thermoluminescence dosimetry, were 4.9-273 mGy (forehead), 14-398 mGy (eyes), 8-433.3 mGy (shoulders), and 4.7-242.5 mGy (thyroid). The in-built recorded Dose Area Product (DAP) values were 74.61-558.55 and 13.17-2825.12 Gy*cm2 for diagnostic and therapeutic procedures, respectively. The mean fluorescence intensity (MFI) on the phosphorylation of γ-H2AX and p53ser-15 was higher in samples obtained post-exposure vs. pre-exposure. However, the increase was statistically significant only for p53ser-15 (P < 0.01). Consistent with γ-H2AX, CDKN1A, FDXR, BAX, DDB2, SESN1, BCL2, MDM2, TNFSF10B, and PCNA showed (non-significant) decreased expression while GADD45A, ATM, and TNFSF9 showed (non-significant) increased expression. Our results suggest that most of the patients had increased DNA damage and altered gene expression after receiving relatively low doses of ionising radiation. This implies that these procedures should be carried out at the lowest possible doses of radiation that do not compromise image quality.


Assuntos
Dano ao DNA , Expressão Gênica/efeitos da radiação , Radiografia Intervencionista/efeitos adversos , Ligante 4-1BB/biossíntese , Ligante 4-1BB/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Mutadas de Ataxia Telangiectasia/biossíntese , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas de Ciclo Celular/biossíntese , Proteínas de Ciclo Celular/genética , Relação Dose-Resposta à Radiação , Feminino , Histonas/genética , Humanos , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Exposição à Radiação , Reação em Cadeia da Polimerase em Tempo Real , Proteína Supressora de Tumor p53/biossíntese , Proteína Supressora de Tumor p53/genética , Adulto Jovem
18.
Artigo em Inglês | MEDLINE | ID: mdl-30678829

RESUMO

Positron Emission Tomography/Computed Tomography (PET/CT), a combination of PET and CT, is used in tumor staging, therapy planning, and treatment response monitoring. During PET imaging, patients receive low doses of radiation, which can induce an adaptive response and necessitate higher doses for therapeutic efficacy. Higher doses may augment toxicity to normal cells. We are examining the effects of short-term, low-dose exposures to ionizing radiation. Entrance Surface Dose (ESD) to head, shoulders, and pelvis regions were measured using Li2B4O7: Mn thermoluminescent dosimeters. Induced DNA damage in lymphocytes was measured using γ-H2AX, p53Ser-15, chromosome aberrations, and micronucleus formation in subjects (n = 25) who underwent 18F-FDG PET/CT. The mean ESD ± SD value obtained were 32.40 ± 16.86, 32.58 ± 14.22, 32.02 ± 15.42, 43.55 ± 18.25 and 42.80 ± 24.67 mGy for the head, right shoulder, left shoulder, right pelvic, and left pelvic regions, respectively. The effective doses of PET and CT ranged from 4.01 to 6.61 and 16.40-72.18 mSv, respectively, and the obtained Dose Length Product (DLP) varied from 1093 to 4812 mGy*cm. There was no correlation between DLP and ESD (r2 = 0.1). The chromosome aberration assay showed a significant increase (p < 0.05), post-scanning vs. pre-scanning; the γ-H2AX, p53Ser-15, and micronucleus assays did not show significant increases. Induced DNA damage showed inter-individual variation among the study subjects. Our results imply that the patients received a biologically significant dose during 18F-PET/CT scanning and precautions may be needed to reduce any long-term risk of exposure.


Assuntos
Aberrações Cromossômicas/efeitos da radiação , Dano ao DNA/efeitos da radiação , Fluordesoxiglucose F18/efeitos adversos , Linfócitos/efeitos da radiação , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/efeitos adversos , Doses de Radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , Radiação Ionizante
19.
Appl Radiat Isot ; 131: 1-7, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29080427

RESUMO

The γ-H2AX assay was investigated as an alternative to the time-consuming dicentric chromosome assay (DCA). Radiation doses to 25 radiotherapy patients were estimated in parallel by DCA and the γ-H2AX assay. The γ-H2AX assay yielded doses in line with the calculated equivalent whole body doses in 92% of the patients, whereas the success rate of DCA was only 76%. The result shows that the γ-H2AX assay can be effectively used as a rapid and more precise alternative to DCA.


Assuntos
Aberrações Cromossômicas , Histonas/genética , Radiometria/métodos , Dosagem Radioterapêutica , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Histonas/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/radioterapia , Reprodutibilidade dos Testes , Irradiação Corporal Total , Adulto Jovem
20.
J Photochem Photobiol B ; 178: 496-504, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29241121

RESUMO

Textile industries release tonnes of harmful toxic dyes into the environment, causing severe effects on living organisms, including humans. Mosquitoes vectors spread important diseases which cause millions of human deaths worldwide. To control mosquitoes a number of synthetic mosquitocidal agents have been employed but all these pesticides pose harmful effects to human health and non-target species and also led to resistance development in treated vectors. Microbial strains are also developing resistance to the available antibiotics, this currently represents a major public health challenge. The current study is focused on the green synthesis of titanium dioxide nanoparticles (TiO2 NPs) using aqueous leaf extracts of Euphorbia hirta. Results suggested an efficient remedy for the above mentioned problems using TiO2 NPs against the dye degradation, mosquito larvae and bacterial pathogens. The fabrication of TiO2 NPs was confirmed by UV-visible spectroscopy, the biomolecules involved in the synthesis process were evidenced by Fourier transform infra-red spectroscopy (FT-IR), the crystalline structure was observed by using X-ray powder diffraction (XRD) analysis. Spherical shaped TiO2NPs were recorded using field emission scanning electron microscopy (FESEM). Energy dispersive X-ray spectroscopy (EDX) results showed the elemental composition of TiO2 NPs. Enhanced rate of photocatalytic dye degradation efficacy was recorded in in methylene blue (95.8%) followed by crystal violet (86.7%). Antibacterial activity assays indicated growth inhibition was highest in Staphylococcus epidermidis and Proteus vulgaris. The LC50 of TiO2 NPs and E. hirta extract on Aedes aegypti larvae were 13.2mg/l and 81.2mg/l, while on Culex quinquefasciatus they were 6.89mg/l and 46.1mg/l respectively. Overall, based on the results of the present study, the green engineered nanotitania could be considered as novel and promising photocatalytic, antibacterial, and mosquitocidal agent.


Assuntos
Anti-Infecciosos/química , Corantes/química , Nanopartículas Metálicas/química , Titânio/química , Aedes/efeitos dos fármacos , Aedes/crescimento & desenvolvimento , Animais , Anti-Infecciosos/farmacologia , Compostos Azo/química , Catálise , Escherichia coli/efeitos dos fármacos , Euphorbia/química , Euphorbia/metabolismo , Química Verde , Larva/efeitos dos fármacos , Luz , Nanopartículas Metálicas/toxicidade , Azul de Metileno/química , Fotólise/efeitos dos fármacos , Fotólise/efeitos da radiação , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos
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