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1.
Life Sci ; 357: 122975, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39142508

RESUMO

Animal models, mainly murine, stay as a fundamental resource in diverse research pursuits, notably contributing to significant strides in discovering novel treatments for therapeutic applications. Preclinical assays must consider the existence of self-recovery mechanisms in the murine species to achieve a well-designed control group. This study focuses on unveiling the innate rapid regenerative capacity of rat liver by utilizing the thioacetamide-induced sub-chronic liver injury model. Employing histopathological, biochemical, and molecular liver function tests, we assessed the recovery of liver tissue functionality. Moreover, animals were housed with voluntary running wheels and locomotory activity was recorded and employed as an indirect index of overall animal recuperation. Remarkably, basal locomotory activity reestablished to normal levels only two weeks post-thioacetamide exposure. Our results raise vital considerations about the importance of temporal synchronicity in comparative assays to validate the real action of treatments, emphasizing the role of the rapid rat liver endogenous self-recovery.

2.
Inflammopharmacology ; 32(5): 3327-3345, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39133352

RESUMO

Wounds or chronic injuries are associated with high medical costs so, develop healing-oriented drugs is a challenge for modern medicine. The identification of new therapeutic alternatives focuses on the use of natural products. Therefore, the main goal of this study was to evaluate the healing potential and anti-inflammatory mechanism of action of extracts and the main compounds derived from Myrciaria plinioides D. Legrand leaves. The antimicrobial activity of leaf extracts was analyzed. Cell viability, cytotoxicity and genotoxicity of plant extracts and compounds were also assessed. Release of pro- and anti-inflammatory cytokines and TGF-ß by ELISA, and protein expression was determined by Western Blot. The cell migration and cell proliferation of ethanol and aqueous leaf extracts and p-coumaric acid, quercetin and caffeic acid compounds were also evaluated. The aqueous extract exhibited antibacterial activity and, after determining the safety concentrations in three assays, we showed that this extract induced p38-α MAPK phosphorylation and the same extract and the p-coumaric acid decreased COX-2 and caspase-3, -8 expression, as well as reduced the TNF-α release and stimulated the IL-10 in RAW 264.7 cells. In L929 cells, the extract and p-coumaric acid induced TGF-ß release, besides increasing the process of cell migration and proliferation. These results suggested that the healing properties of Myrciaria plinioides aqueous extract can be associated to the presence of phenolic compounds, especially p-coumaric acid, and/or glycosylated metabolites.


Assuntos
Anti-Inflamatórios , Movimento Celular , Extratos Vegetais , Folhas de Planta , Cicatrização , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Cicatrização/efeitos dos fármacos , Camundongos , Células RAW 264.7 , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular , Citocinas/metabolismo , Myrtaceae/química , Ácidos Cumáricos/farmacologia , Ácidos Cumáricos/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/isolamento & purificação
3.
Environ Monit Assess ; 196(8): 773, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39090345

RESUMO

Rodents are considered good models for investigating genotoxic damage and mutagenic alterations caused by xenobiotic agents, due to their occupation of a wide variety of habitats. However, relatively few in situ studies have focused on DNA damage in wild rodents associated with environmental exposure. In this review, we investigate trends in the application of the micronucleus test and comet assay in in situ studies of wild rodents. A total of 33 papers were identified, distributed across 14 different countries. Brazil and Spain had the most published studies (six each), followed by Bulgaria (n = 5), Mexico (n = 4) and Italy (n = 3). Only 24 of the 2,652 recognized rodent species have been the subject of in situ studies, which have most frequently focus on species of the genus Mus. The protocols used for the micronucleus test and comet assay varied widely, although blood and bone marrow were the primary types of tissue used. Given the paucity of studies on wild rodents, we recommend further research, particularly focusing on the use of this group as bioindicators of environmental quality and the standardization of protocols.


Assuntos
Ensaio Cometa , Dano ao DNA , Monitoramento Ambiental , Testes para Micronúcleos , Roedores , Ensaio Cometa/métodos , Testes para Micronúcleos/métodos , Animais , Monitoramento Ambiental/métodos , Animais Selvagens , Poluentes Ambientais/toxicidade
4.
Environ Int ; 190: 108907, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39121825

RESUMO

Environmental exposures and gene-exposure interactions are the major causes of some diseases. Early-life exposome studies are needed to elucidate the role of environmental exposures and their complex interactions with biological mechanisms involved in childhood health. This study aimed to determine the contribution of early-life exposome to DNA damage and the modifying effect of genetic polymorphisms involved in air pollutants metabolism, antioxidant defense, and DNA repair. We conducted a cohort study in 416 Colombian children under five years. Blood samples at baseline were collected to measure DNA damage by the Comet assay and to determine GSTT1, GSTM1, CYP1A1, H2AX, OGG1, and SOD2 genetic polymorphisms. The exposome was estimated using geographic information systems, remote sensing, LUR models, and questionnaires. The association exposome-DNA damage was estimated using the Elastic Net linear regression with log link. Our results suggest that exposure to PM2.5 one year before the blood draw (BBD) (0.83, 95 %CI: 0.76; 0.91), soft drinks consumption (0.94, 0.89; 0.98), and GSTM1 null genotype (0.05, 0.01; 0.36) diminished the DNA damage, whereas exposure to PM2.5 one-week BBD (1.18, 1.06; 1.32), NO2 lag-5 days BBD (1.27, 1.18; 1.36), in-house cockroaches (1.10, 1.00; 1.21) at the recruitment, crowding at home (1.34, 1.08; 1.67) at the recruitment, cereal consumption (1.11, 1.04; 1.19) and H2AX (AG/GG vs. AA) (1.44, 1.11; 1.88) increased the DNA damage. The interactions between H2AX (AG/GG vs. AA) genotypes with crowding and PM2.5 one week BBD, GSTM1 (null vs. present) with humidity at the first year of life, and OGG1 (SC/CC vs. SS) with walkability at the first year of life were significant. The early-life exposome contributes to elucidating the effect of environmental exposures on DNA damage in Colombian children under five years old. The exposome-DNA damage effect appears to be modulated by genetic variants in DNA repair and antioxidant defense enzymes.


Assuntos
Poluentes Atmosféricos , Dano ao DNA , Exposição Ambiental , Interação Gene-Ambiente , Humanos , Pré-Escolar , Colômbia , Masculino , Feminino , Lactente , Expossoma , Estudos de Coortes , Glutationa Transferase/genética , Material Particulado , Polimorfismo Genético , Poluição do Ar/efeitos adversos , Poluição do Ar/estatística & dados numéricos
5.
Neotrop Entomol ; 53(5): 1168-1171, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38995502

RESUMO

We report for the first time that larvae of the genus Bothynus Hope (Coleoptera: Melolonthidae) caused economic damage to lucerne (Medicago sativa L., Fabaceae) crops in General Acha, province of La Pampa, Argentina. In two consecutive years (2021 and 2022), this insect infested 150 ha of lucerne, causing seedling losses of 80 ha. Based on soil sampling and laboratory insect rearing, the species was identified as Bothynus striatellus (Faimaire) (Coleoptera: Melolonthidae). Information is given here on the damage recorded in this forage crop, the density of the larvae observed at the time of damage assessment and the morphological characteristics of the third instar larvae reported in this crop in Argentina.


Assuntos
Besouros , Produtos Agrícolas , Larva , Medicago sativa , Animais , Argentina
6.
Saf Health Work ; 15(2): 236-241, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39035798

RESUMO

Background: Gasoline, a complex mixture of volatile organic compounds is classified as possibly carcinogenic to humans. Gasoline station attendants, consistently exposed to its hazardous components, may face genotoxic effects. This study aimed to assess the influence of varying work shift durations on DNA damage in gasoline station attendants. Methods: Ninety individuals from three locations in southern México were studied. Peripheral blood mononuclear cells (PBMCs) were isolated, and DNA damage was assessed using the comet assay. Demographic, occupational, and lifestyle data were collected. Statistical analyses included t-tests, ANOVA, and Pearson correlation. Results: Significant differences in DNA damage parameters were observed between exposed and unexposed groups. The impact of tobacco, alcohol, and exercise on DNA damage was negligible. Extended work shifts (12 and 24 hours) showed heightened DNA damage compared to 8-hour shifts and the unexposed group. A novel finding revealed a modest but significant correlation between DNA damage and job seniority. Conclusion: The study highlights the intricate relationship between occupational exposure to gasoline components, DNA damage, and work shift lengths. Extended shifts correlate with heightened genotoxic effects, emphasizing the importance of personalized safety measures. The significant correlation between DNA damage and job seniority introduces occupational longevity as a determinant in the genetic health of gasoline station attendants. This discovery has implications for implementing targeted interventions and preventive strategies to safeguard workers' genetic integrity throughout their years of service. The study calls for further exploration of unconsidered factors in understanding the multifactorial nature of DNA damage in this occupational setting.

7.
Biology (Basel) ; 13(7)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39056661

RESUMO

BACKGROUND: Human beings consume different chemical forms of iodine in their diet. These are transported by different mechanisms in the cell. The forms of iodine can be part of thyroid hormones, bind to lipids, be an antioxidant, or be an oxidant, depending on their chemical form. The excessive consumption of iodine has been associated with pancreatic damage and diabetes mellitus type 2, but the association between disease and the chemical form consumed in the diet is unknown. This research analyzes the effect of excessive iodine consumption as Lugol (molecular iodine/potassium iodide solution) and iodate on parameters of pancreatic function, thyroid and lipid profiles, antioxidant and oxidant status, the expression of IR/Akt/P-Akt/GLUT4, and transcription factors PPAR-γ and CEBP-ß. METHODS: Three groups of Wistar rats were treated with 300 µg/L of iodine in drinking water: (1) control, (2) KIO3, and (3) Lugol. RESULTS: Lugol and KIO3 consumption increased total iodine levels. Only KIO3 increased TSH levels. Both induced high serum glucose levels and increased oxidative stress and pancreatic alpha-amylase activity. Insulin levels and antioxidant status decreased significantly. PPAR-γ and C/EBP-ß mRNA expression increased. CONCLUSION: The pancreatic damage, hypertriglyceridemia, and oxidative stress were independent of the chemical form of iodine consumed. These effects depended on PPAR-γ, C/EBP-ß, GLUT-4, and IR.

8.
Am J Physiol Endocrinol Metab ; 327(3): E302-E312, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39018175

RESUMO

Acute kidney injury (AKI) is a public health concern associated with high rates of mortality, even in milder cases. One of the reasons for the difficulty in managing AKI in patients is due to its association with pre-existing comorbidities, such as diabetes. In fact, diabetes increases the susceptibility to develop more severe AKI after renal ischemia. However, the long-term effects of this association are not known. Thus, an experimental model was designed to evaluate the chronic effects of renal ischemia/reperfusion (IR) in streptozotocin (STZ)-treated mice. We focused on the glomerular and tubulointerstitial damage, as well as kidney function and metabolic profile. It was found that pre-existing diabetes may potentiate progressive kidney disease after AKI, mainly by exacerbating proinflammatory and sustaining fibrotic responses and altering renal glucose metabolism. To our knowledge, this is the first report that highlights the long-term effects of renal IR on diabetes. The findings of this study can support the management of AKI in clinical practice.NEW & NOTEWORTHY This study demonstrated that early diabetes potentiates progressive kidney disease after ischemia/reperfusion (IR)-induced acute kidney injury, mainly by exacerbating pro-inflammatory and sustaining fibrotic responses and altering renal glucose metabolism. Thus, these findings will contribute to the therapeutic support of patients with type 1 diabetes with eventual renal IR intervention in clinical practice.


Assuntos
Injúria Renal Aguda , Diabetes Mellitus Experimental , Nefropatias Diabéticas , Progressão da Doença , Rim , Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/patologia , Camundongos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Masculino , Rim/metabolismo , Rim/patologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/etiologia , Camundongos Endogâmicos C57BL , Estreptozocina , Fibrose
9.
Plant J ; 119(4): 2021-2032, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38963754

RESUMO

DNA glycosylases initiate the base excision repair (BER) pathway by catalyzing the removal of damaged or mismatched bases from DNA. The Arabidopsis DNA glycosylase methyl-CpG-binding domain protein 4 like (MBD4L) is a nuclear enzyme triggering BER in response to the genotoxic agents 5-fluorouracil and 5-bromouracil. To date, the involvement of MBD4L in plant physiological processes has not been analyzed. To address this, we studied the enzyme functions in seeds. We found that imbibition induced the MBD4L gene expression by generating two alternative transcripts, MBD4L.3 and MBD4L.4. Gene activation was stronger in aged than in non-aged seeds. Seeds from mbd4l-1 mutants displayed germination failures when maintained under control or ageing conditions, while 35S:MBD4L.3/mbd4l-1 and 35S:MBD4L.4/mbd4l-1 seeds reversed these phenotypes. Seed nuclear DNA repair, assessed by comet assays, was exacerbated in an MBD4L-dependent manner at 24 h post-imbibition. Under this condition, the BER genes ARP, APE1L, and LIG1 showed higher expression in 35S:MBD4L.3/mbd4l-1 and 35S:MBD4L.4/mbd4l-1 than in mbd4l-1 seeds, suggesting that these components could coordinate with MBD4L to repair damaged DNA bases in seeds. Interestingly, the ATM, ATR, BRCA1, RAD51, and WEE1 genes associated with the DNA damage response (DDR) pathway were activated in mbd4l-1, but not in 35S:MBD4L.3/mbd4l-1 or 35S:MBD4L.4/mbd4l-1 seeds. These results indicate that MBD4L is a key enzyme of a BER cascade that operates during seed imbibition, whose deficiency would cause genomic damage detected by DDR, generating a delay or reduction in germination.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , DNA Glicosilases , Reparo do DNA , Germinação , Sementes , Sementes/genética , Sementes/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , DNA Glicosilases/metabolismo , DNA Glicosilases/genética , Regulação da Expressão Gênica de Plantas , Dano ao DNA
10.
Environ Sci Pollut Res Int ; 31(34): 47116-47131, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38985418

RESUMO

Mining is a major economic activity in many developing countries. However, it disturbs the environment, producing enormous quantities of waste, known as mine tailings, which can have deleterious environmental impact, due to their high heavy metals (HM) content. Often, foundation species that establish on mine tailings are good candidates to study the effects of HM bioaccumulation at different levels of biological organization. Prosopis laevigata is considered a HM hyperaccumulator which presents attributes of a foundation species (FS) and establishes naturally on mine tailings. We evaluated the bioaccumulation of Cu, Pb, and Zn in P. laevigata foliar tissue, the leaf micro- and macro-morphological characters, DNA damage, and population genetic effects. In total, 80 P. laevigata individuals (20/site) belonging to four populations: The individuals from both sites (exposed and reference) bioaccumulated HMs (Pb > Cu > Zn). However, in the exposed individuals, Pb and Cu bioaccumulation was significantly higher. Also, a significant effect of macro- and micro-morphological characters was registered, showing significantly lower values in individuals from the exposed sites. In addition, we found significant differences in genotoxic damage in P. laevigata individuals, between the exposed and reference sites. In contrast, for the micro-morphological characters, none of the analyzed metals had any influence. P. laevigata did not show significant differences in the genetic structure and diversity between exposed and reference populations. However, four haplotypes and four private alleles were found in the exposed populations. Since P. laevigata is a species that establishes naturally in polluted sites and bioaccumulates HM in its foliar tissues, the resulting genetic, individual and population effects have not been severe enough to show detrimental effects; hence, P. laevigata can be a useful tool in phytoremediation strategies for soils polluted with Pb and Cu, maintaining its important ecological functions.


Assuntos
Bioacumulação , Metais Pesados , Prosopis , Poluentes do Solo , Metais Pesados/metabolismo , Prosopis/metabolismo , Poluentes do Solo/metabolismo , Biomarcadores/metabolismo , Mineração , Monitoramento Ambiental/métodos
11.
J Therm Biol ; 123: 103923, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39067196

RESUMO

Skin temperature responses have been advocated to indicate exercise-induced muscle soreness and recovery status. While the evidence is contradictory, we hypothesize that the presence of muscle damage and the time window of measurement are confounding factors in the skin temperature response. The objective was to determine whether skin temperature is influenced by different workloads and the time course of temperature measurements over the following 24 h. 24 trained male military were assigned to one of three groups: GC group (n = 8) serving as control not performing exercises, GE group (n = 8) performing a simulated military combat protocol in an exercise track with different obstacles but designed not to elicit muscle damage, and the GEMD group (n = 8) performing the simulated military combat protocol plus 5 sets of 20 drop jumps, with 10-sec between repetitions and with 2-min of rest between sets aiming to induce muscle damage. Skin temperature was measured using infrared thermography before exercise (Pre) and 4 (Post4h), 8 (Post8h) and 24h (Post24h) post-exercise. Perception of pain (DOMS) was evaluated Pre, Post24h, and Post48h, and countermovement jump height was evaluated at Pre and Post24h. DOMS did not differ between groups in the Pre and Post24h measures but GEMD presented higher DOMS than the other groups at Post48h (p < 0.001 and large effect size). Jump height did not differ for GEMD and GC, and GE presented higher jump height at Post24h than GC (p = 0.02 and large effect size). Skin temperature responses of GEMD and GG were similar in all measurement moments (p > 0.22), and GE presented higher skin temperature than the GC and the GEMD groups at Post24h (p < 0.01 and large effect sizes). In conclusion, although physical exercise elicits higher skin temperature that lasts up to 24 h following the efforts, muscle soreness depresses this response.


Assuntos
Exercício Físico , Mialgia , Temperatura Cutânea , Humanos , Masculino , Adulto , Mialgia/fisiopatologia , Adulto Jovem , Militares
12.
Neurotox Res ; 42(4): 33, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963434

RESUMO

The white matter is an important constituent of the central nervous system, containing axons, oligodendrocytes, and its progenitor cells, astrocytes, and microglial cells. Oligodendrocytes are central for myelin synthesis, the insulating envelope that protects axons and allows normal neural conduction. Both, oligodendrocytes and myelin, are highly vulnerable to toxic factors in many neurodevelopmental and neurodegenerative disorders associated with disturbances of myelination. Here we review the main alterations in oligodendrocytes and myelin observed in some organic acidurias/acidemias, which correspond to inherited neurometabolic disorders biochemically characterized by accumulation of potentially neurotoxic organic acids and their derivatives. The yet incompletely understood mechanisms underlying the high vulnerability of OLs and/or myelin in glutaric acidemia type I, the most prototypical cerebral organic aciduria, are particularly discussed.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Encefalopatias Metabólicas , Glutaril-CoA Desidrogenase , Oligodendroglia , Substância Branca , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Erros Inatos do Metabolismo dos Aminoácidos/patologia , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Glutaril-CoA Desidrogenase/deficiência , Glutaril-CoA Desidrogenase/metabolismo , Humanos , Animais , Substância Branca/patologia , Substância Branca/metabolismo , Encefalopatias Metabólicas/patologia , Encefalopatias Metabólicas/metabolismo , Bainha de Mielina/metabolismo , Bainha de Mielina/patologia
13.
J Infect Dis ; 230(1): e60-e64, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39052712

RESUMO

In 2018 there was a large yellow fever outbreak in São Paulo, Brazil, with a high fatality rate. Yellow fever virus can cause, among other symptoms, hemorrhage and disseminated intravascular coagulation, indicating a role for endothelial cells in disease pathogenesis. Here, we conducted a case-control study and measured markers related to endothelial damage in plasma and its association with mortality. We found that angiopoietin 2 is strongly associated with a fatal outcome and could serve as a predictive marker for mortality. This could be used to monitor severe cases and provide care to improve disease outcome.


Assuntos
Angiopoietina-2 , Biomarcadores , Febre Amarela , Vírus da Febre Amarela , Humanos , Estudos de Casos e Controles , Febre Amarela/mortalidade , Febre Amarela/sangue , Febre Amarela/virologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Angiopoietina-2/sangue , Biomarcadores/sangue , Brasil/epidemiologia , Idoso , Adulto Jovem
14.
J Clin Med ; 13(13)2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38999430

RESUMO

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

15.
Int J Mol Sci ; 25(13)2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-39000531

RESUMO

Epitranscriptomics is a field that delves into post-transcriptional changes. Among these modifications, the conversion of adenosine to inosine, traduced as guanosine (A>I(G)), is one of the known RNA-editing mechanisms, catalyzed by ADARs. This type of RNA editing is the most common type of editing in mammals and contributes to biological diversity. Disruption in the A>I(G) RNA-editing balance has been linked to diseases, including several types of cancer. Drug resistance in patients with cancer represents a significant public health concern, contributing to increased mortality rates resulting from therapy non-responsiveness and disease progression, representing the greatest challenge for researchers in this field. The A>I(G) RNA editing is involved in several mechanisms over the immunotherapy and genotoxic drug response and drug resistance. This review investigates the relationship between ADAR1 and specific A>I(G) RNA-edited sites, focusing particularly on breast cancer, and the impact of these sites on DNA damage repair and the immune response over anti-cancer therapy. We address the underlying mechanisms, bioinformatics, and in vitro strategies for the identification and validation of A>I(G) RNA-edited sites. We gathered databases related to A>I(G) RNA editing and cancer and discussed the potential clinical and research implications of understanding A>I(G) RNA-editing patterns. Understanding the intricate role of ADAR1-mediated A>I(G) RNA editing in breast cancer holds significant promise for the development of personalized treatment approaches tailored to individual patients' A>I(G) RNA-editing profiles.


Assuntos
Adenosina Desaminase , Neoplasias da Mama , Edição de RNA , Proteínas de Ligação a RNA , Humanos , Adenosina Desaminase/genética , Adenosina Desaminase/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Feminino , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Adenosina/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Inosina/metabolismo , Inosina/genética , Animais , Guanosina/metabolismo , Dano ao DNA
16.
Artigo em Inglês | MEDLINE | ID: mdl-39054010

RESUMO

The presence of arsenic in the environment is a public health problem. Groundwater of certain regions of Argentina contains arsenic of natural origin in concentrations that exceed the guide level recommended by World Health Organization (WHO, 10 µg/L). Pathologies derived from chronic arsenic consumption justify the planning of human biomonitoring. Hence, the aim of this study was to evaluate oxidative damage and genotoxicity and its relationship with nutritional variables in populations exposed to arsenic through drinking water in Santa Fe province, Argentina. A total of 322 participants were analyzed for arsenic in urine together with biomarkers of genotoxicity (Comet assay in blood and frequency of Micronuclei and other Nuclear Abnormalities in exfoliated buccal cells) and oxidative stress (modified Comet assay with Endonuclease III, Lipid peroxidation and antioxidant enzyme activity), as well as nutritional and biochemical variables. Results showed that 45 % of participants excreted arsenic in the urine. Consumption of water with arsenic, whether currently or previously, was associated with statistically significant increase of oxidative DNA damage and lipid peroxidation. MN in exfoliated buccal cells serve as an early biomarker of genotoxicity and showed significant differences in the current exposed group. Biochemical results indicate dyslipidemias potentially linked to dietary choices, and insufficient intake of fruits and vegetables rich in antioxidants, was also noted. This study advocates risk communication to the population, educators, and health authorities, emphasizing the need for preventive health strategies and improved food education.


Assuntos
Arsênio , Dano ao DNA , Água Potável , Estresse Oxidativo , Poluentes Químicos da Água , Humanos , Argentina/epidemiologia , Arsênio/toxicidade , Arsênio/urina , Água Potável/análise , Água Potável/química , Estresse Oxidativo/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Feminino , Masculino , Adulto , Poluentes Químicos da Água/toxicidade , Pessoa de Meia-Idade , Ensaio Cometa , Peroxidação de Lipídeos/efeitos dos fármacos , Adulto Jovem , Adolescente , Idoso , Testes para Micronúcleos , Exposição Ambiental/efeitos adversos
17.
Artigo em Inglês | MEDLINE | ID: mdl-39054011

RESUMO

The extraction and burning of coal release genotoxic pollutants, and understanding the relationship between genetic damage and the spatial distribution of residences in coal-using regions is crucial. The study aimed to conduct a spatial analysis of genotoxic damage through the of micronuclei (MNs) number and their proximity to coal mining/burning in the largest coal exploration region in Brazil. In this study, the detection of genotoxic damage was performed using the MN assay in oral cells of residents exposed to coal mining activities. Spatial analysis was conducted using QGIS 3.28.10 based on information obtained from a questionnaire administered to the population. Multiple linear regression analysis was carried out to assess the influence of the distance from residential areas to polluting sources on the number of MNs found. Additionally, Spearman's correlation was performed to identify the strength and direction of the association between the frequency of MNs and each of the polluting sources. A total of 147 MNs were quantified among all participants in the coal mining region. Notably, residents living within 2 km and 10 km of pollution sources exhibited the highest prevalence of MNs. The analysis demonstrated a significant correlation between closer proximity to pollution sources and increased MN frequency, underscoring the spatial relationship between these sources and genotoxic damage. Environmental pollutants from anthropogenic sources present a major health risk, potentially leading to irreversible damage. The spatial analysis in this study highlights the importance of targeted public policies. These policies should aim for a sustainable balance between economic development and public health, promoting effective measures to mitigate environmental impacts and protect community health.


Assuntos
Minas de Carvão , Micronúcleos com Defeito Cromossômico , Testes para Micronúcleos , Mucosa Bucal , Brasil , Humanos , Mucosa Bucal/citologia , Micronúcleos com Defeito Cromossômico/estatística & dados numéricos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Adulto , Masculino , Exposição Ambiental/efeitos adversos , Feminino , Pessoa de Meia-Idade , Dano ao DNA , Análise Espacial , Adulto Jovem
18.
Environ Res ; 258: 119282, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823611

RESUMO

The Villa Victoria dam is one of the most important storage reservoirs in Mexico since it distributes water to more than 20 million inhabitants in the Metropolitan Zone of Mexico City. In this dam, the common carp (Cyprinus carpio) is an important food resource for the inhabitants, so the aim of this work was to evaluate the oxidative damage (lipoperoxidation, oxidized proteins, antioxidant enzymes activity and gene expression), AChE, embryotoxicity and behavioral changes in C. carpio embryos and larvae exposed to water from Villa Victoria dam for 24, 48, 72 and 96 h. The embryotoxicity was evaluated trough the General Morphology Score (GMS) and the teratogenic index. Behavioral changes in basal locomotor activity and thigmotaxis were evaluated in a DanioVision, Noldus ™. An increase in lipid and protein oxidation as well as modification of CAT, SOD and GPx enzymatic activity was observed during the exposure times. The GMS indicated a low development in the embryos, the teratogenic index was less than 1, however teratogenic effects as yolk edema, fin malformation, head malformation and scoliosis were observed. In parallel, an increase in AChE activity and gene expression was observed reflecting changes in distance traveled of the basal locomotor activity and thigmotaxis at the sampling points. In conclusion, pollutants in water from Villa Victoria dam caused oxidative damage, changes in SOD, CAT, GPx and AChE activity as well as embryotoxicity and modifications in the behavior of C. carpio larvae. This study demonstrates the need to implement restoration programs for this reservoir since, contamination in the Villa Victoria dam could eventually endanger aquatic life and human health.


Assuntos
Acetilcolinesterase , Carpas , Embrião não Mamífero , Larva , Estresse Oxidativo , Poluentes Químicos da Água , Animais , Poluentes Químicos da Água/toxicidade , Estresse Oxidativo/efeitos dos fármacos , México , Acetilcolinesterase/metabolismo , Carpas/embriologia , Carpas/metabolismo , Larva/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos
19.
Neotrop Entomol ; 53(4): 1002-1008, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38833136

RESUMO

This is the first record of Melanoloma viatrix Hendel as well as in its host (pineapple) in Brazil. Previously, M. viatrix had been found in pineapple plantations in Peru, Colombia, Venezuela, and Ecuador. In Brazil, this fly was initially reported in pineapple purchased from a commercial establishment in the municipality of Porto Grande, Amapá State, in 2020. Subsequently, M. viatrix was found in a commercial pineapple plantation, Ananas comosus (L.) Merr. cv. Pérola, also in Porto Grande, Amapá State. In the pineapple samples, 2,320 specimens of M. viatrix were collected on a single day on that rural property (approximately 2 ha). The larvae open galleries in the pulp that cause the pineapple to rot, making it unviable for consumption and commercial sale. This communication aims to alert phytosanitary authorities of the need to establish control strategies to prevent the spread of the pineapple fly to other states in Brazil.


Assuntos
Ananas , Dípteros , Larva , Brasil , Animais
20.
Per Med ; 21(4): 243-255, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38940364

RESUMO

Aim: Compare two vancomycin dosing strategies in critical patients with methicillin-resistant Staphylococcus aureus (MRSA) infections, considering the heterogeneity of the dosing regimens administered and their implications for toxicity and efficacy. Materials & methods: Longitudinal retrospective observational study in two patient cohorts (standard dosing vs dosing via Bayesian algorithms). Results: The group of Bayesian algorithms received substantially higher and significantly heterogeneous doses, with an absence of nephrotoxicity. The speed of decrease observed in CRP and PCT was greater for the Bayesian strategy (p = 0.045 and 0.0009, respectively). Conclusion: Applying Bayesian algorithms to vancomycin dosage individualization allows for administering much higher doses than with standard regimens, facilitating a quicker clinical response in the absence of nephrotoxicity.


[Box: see text].


Assuntos
Algoritmos , Antibacterianos , Teorema de Bayes , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Vancomicina , Humanos , Vancomicina/administração & dosagem , Estudos Retrospectivos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Longitudinais , Idoso , Medicina de Precisão/métodos , Estado Terminal , Adulto
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