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New generation of nanomaterials with organelle-level precision provide significant promise for targeted attacks on mitochondria, exhibiting remarkable therapeutic potency. Here, we report a novel amphiphilic phenolic polymer (PF) for the mitochondria-targeted photodynamic therapy (PDT), which can trigger excessive mitochondrial DNA (mtDNA) damages by the synergistic action of oxidative stress and furan-mediated DNA cross-linking. Moreover, the phenolic units on PF enable further self-assembly with Mn2+ via metal-phenolic coordination to form metal-phenolic nanomaterial (PFM). We focus on the synergistic activation of the cGAS-STING pathway by Mn2+ and tumor-derived mtDNA in tumor-associated macrophages (TAMs), and subsequently repolarizing M2-like TAMs to M1 phenotype. We highlight that PFM facilitates the cGAS-STING-dependent immunity at the organelle level for potent antitumor efficacy.
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When an ultrasonic pulse propagates in a thin plate, nonlinear Lamb waves with higher harmonics and a zero-frequency component (ZFC) will be generated because of the nonlinearity of materials. The ZFC, also known as the static displacement or static component, has its unique application on the evaluation of early-stage damages in the elastic symmetrical undulated plate. In this study, analysis of the excitation mechanism of the ZFC and the second harmonic component (SHC) was theoretically and numerically investigated, and the material early-stage damage of a symmetrical undulated was characterized by studying the propagation of nonlinear Lamb waves. Both the ZFC and SHC can be effectively employed in monitoring the material damages of the undulated plate in its early stage. However, several factors must be considered for the propagation of the SHC in an undulated plate because of the geometric curvature and interference between the second harmonics during propagation, preventing efficient application of this technique. If the fundamental wave can propagate in the plate regardless of the plate boundary conditions, an accumulative effect always exists for the ZFC in a thin plate, indicating that the ZFC is independent of the structural geometry. This study reveals that the ZFC-based inspection technique is more efficient and powerful in characterizing the damages of a symmetrical undulated plate in the early stage of service compared to the second harmonic method.
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Exposure to ionizing radiation can induce genetic aberrations via unrepaired DNA strand breaks. To investigate quantitatively the dose-effect relationship at the molecular level, we irradiated dry pBR322 plasmid DNA with 3 MeV protons and assessed fragmentation yields at different radiation doses using long-read sequencing from Oxford Nanopore Technologies. This technology applied to a reference DNA model revealed dose-dependent fragmentation, as evidenced by read length distributions, showing no discernible radiation sensitivity in specific genetic sequences. In addition, we propose a method for directly measuring the single-strand break (SSB) yield. Furthermore, through a comparative study with a collection of previous works on dry DNA irradiation, we show that the irradiation protocol leads to biases in the definition of ionizing sources. We support this scenario by discussing the size distributions of nanopore sequencing reads in the light of Geant4 and Geant4-DNA simulation toolkit predictions. We show that integrating long-read sequencing technologies with advanced Monte Carlo simulations paves a promising path toward advancing our comprehension and prediction of radiation-induced DNA fragmentation.
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Fragmentação do DNA , Método de Monte Carlo , Plasmídeos , Plasmídeos/genética , Fragmentação do DNA/efeitos da radiação , Relação Dose-Resposta à Radiação , Análise de Sequência de DNA/métodos , Quebras de DNA de Cadeia Simples/efeitos da radiação , DNA/genéticaRESUMO
In clinics, chemotherapy is often combined with surgery and radiation to increase the chances of curing cancers. In the case of glioblastoma (GBM), patients are treated with a combination of radiotherapy and TMZ over several weeks. Despite its common use, the mechanism of action of the alkylating agent TMZ has not been well understood when it comes to its cytotoxic effects in tumor cells that are mostly non-dividing. The cellular response to alkylating DNA damage is operated by an intricate protein network involving multiple DNA repair pathways and numerous checkpoint proteins that are dependent on the type of DNA lesion, the cell type, and the cellular proliferation state. Among the various alkylating damages, researchers have placed a special on O6-methylguanine (O6-mG). Indeed, this lesion is efficiently removed via direct reversal by O6-methylguanine-DNA methyltransferase (MGMT). As the level of MGMT expression was found to be directly correlated with TMZ efficiency, O6-mG was identified as the critical lesion for TMZ mode of action. Initially, the mode of action of TMZ was proposed as follows: when left on the genome, O6-mG lesions form O6-mG: T mispairs during replication as T is preferentially mis-inserted across O6-mG. These O6-mG: T mispairs are recognized and tentatively repaired by a post-replicative mismatched DNA correction system (i.e., the MMR system). There are two models (futile cycle and direct signaling models) to account for the cytotoxic effects of the O6-mG lesions, both depending upon the functional MMR system in replicating cells. Alternatively, to explain the cytotoxic effects of alkylating agents in non-replicating cells, we have proposed a "repair accident model" whose molecular mechanism is dependent upon crosstalk between the MMR and the base excision repair (BER) systems. The accidental encounter between these two repair systems will cause the formation of cytotoxic DNA double-strand breaks (DSBs). In this review, we summarize these non-exclusive models to explain the cytotoxic effects of alkylating agents and discuss potential strategies to improve the clinical use of alkylating agents.
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Quebras de DNA de Cadeia Dupla , Reparo do DNA , Humanos , Reparo do DNA/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Alquilação , Temozolomida/farmacologia , DNA/metabolismo , Antineoplásicos Alquilantes/farmacologia , Animais , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioblastoma/genética , O(6)-Metilguanina-DNA Metiltransferase/metabolismo , O(6)-Metilguanina-DNA Metiltransferase/genéticaRESUMO
Until the discovery of the gene for cystic fibrosis (CF) in 1989, diagnostic developments were limited, and treatment focused on symptom alleviation. However, following the genetic breakthrough, some 2,000 mutations of the gene have been identified. More recently CF transmembrane conductance regulator modulator triple therapy (CFTRm) has been introduced in the form of triple therapy with ivacaftor, lumacaftor and tezacaftor (ETI), in the United States from 2019, Europe from 2020 and then Australia from 2021. The new treatment option has revolutionised both the quality of life and life expectancy of many persons diagnosed with CF. This editorial reviews major developments in the clinical care that can now be provided to patients, and reflects on the legal and ethical ramifications of the improved situation for many patients in the contexts of medical negligence, damages assessment, family law and criminal law. It also considers the difficult issues of access and equity caused by the limited availability of the triple therapy in low- and middle-income countries.
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Aminofenóis , Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Quinolonas , Humanos , Quinolonas/uso terapêutico , Aminofenóis/uso terapêutico , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Aminopiridinas/uso terapêutico , Benzodioxóis/uso terapêutico , Indóis/uso terapêutico , Austrália , Imperícia/legislação & jurisprudência , Estados UnidosRESUMO
The stingless bee Frieseomelitta varia Lepeletier 1836 (Hymenoptera: Apidae) is an essential pollinator in natural and agricultural ecosystems in the Neotropical region. However, these bees may be exposed to pesticides during foraging, which can affect both individuals and their colonies. One example comes from the use of pyraclostrobin (a fungicide) and thiamethoxam (an insecticide) for pest control in pepper crops, which F. varia visits. This study aimed to evaluate the isolated and combined sublethal effects of thiamethoxam (TMX) (0.000543 ng a.i./µL) and pyraclostrobin (PYR) (1.5 ng i.a./µL) on the morphology of the midgut and Malpighian tubules of F. varia workers. Results showed that both pesticides, regardless of the exposure time (through feeding during 48 h or 96 h), disturbed the morphology of the analyzed organs. Specifically, F. varia exposed orally to sublethal concentrations of thiamethoxam and pyraclostrobin, either alone or in combination, exhibited a higher rate of damage to the midgut (e.g., vacuolization, apocrine secretion, and cellular elimination) compared to the bees in the control groups, both after 48 h and 96 h of exposure. In Malpighian tubules, vacuolation is the only damage present. As the observed morphological alterations likely compromise the excretion and absorption functions, exposure to pyraclostrobin and thiamethoxam may lead to disturbances at both the individual and colony levels. These results highlight the urgent need for a future reassessment of the safety of fungicides and insecticides regarding their potential effects on bee populations.
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Introduction: Olive cultivation, like other evergreen fruit crops worldwide, is limited by the occurrence of frost episodes in different times of the year, mainly in winter or early spring. Some contradictory results are reported about cultivars' response to frost, which depends on the physiological stage of the tissues (acclimated or not acclimated) when the cold or frost episode occurs. This work aimed to implement a user-friendly and reliable lab method for discerning frost tolerance. Methods: Our methodology considered both detached leaves and potted plantlets. The optimal temperature at which damage differentiated between cultivars was evaluated, as well as the time of exposure to cold and the recovery time for the correct evaluation of the symptoms. Furthermore, a comparative analysis of damage on both young and mature leaves was conducted. To validate the efficacy of the methodology, assessments were conducted on the cultivars 'Arbequina' (tolerant), 'Picual' (moderately tolerant), and 'Frantoio' (susceptible) under acclimated and non-acclimated conditions. Results and discussion: The results indicated that, when detached leaves were used for frost evaluation, a temperature of -10°C ± 1°C for 30 min and a recovery time at 26°C for 24-48 h after exposure to cold are enough to induce damages on the leaves and discriminate between cultivar susceptibility. Under these conditions, a precise assessment of symptoms can be made, facilitating the categorization of frost tolerance level in various olive cultivars. Notably, no significant differences were observed between young and mature leaves during the evaluation process. On the other hand, the critical temperature to assess damages on potted plantlets was determined to be -7°C ± 1°C. In addition, it was observed that acclimated plants exhibited fewer symptoms compared to non-acclimated ones, with 'Frantoio' being the most affected alongside 'Picual' and 'Arbequina'. Conclusion: The implemented methodology will allow the assessment of frost tolerance in several olive cultivars within a short timeframe, and it is proven to be user-friendly and reliable.
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Traumatic Brain Injury (TBI) cases often involve both medical and legal issues, litigation and prolonged recovery timelines. As TBI cases are often complex, and can have a significant impact on the lives of the patients and their families/caregivers, having a comprehensive understanding of the causes, diagnoses, treatments and long term outcomes will be valuable in understanding the medical and legal aspects of this type of injury. Patients, families, and health care professionals will all benefit from a deeper understanding of the medical and legal aspects of TBI, which should help improve rehabilitation and recovery outcomes.
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Lesões Encefálicas Traumáticas , Humanos , Lesões Encefálicas Traumáticas/reabilitaçãoRESUMO
This paper presents a literature review on the economic valuation of Harmful Algal Bloom (HAB) impacts, identifying methodological challenges, policy implications, and gaps. Unlike previous literature reviews, we are particularly interested in determining whether the economic valuations of HABs have included a policy analysis. Our paper provides a conceptual framework that allows us to evaluate whether applications of economic studies of HABs are consistent with a well-defined economic welfare analysis. It links methodologies and techniques with welfare measures, data types, and econometric methods. Based on this literature review, we present an example of economic valuation that closes the gap between policy analysis and valuation methodology. We use a stated preferences study to estimate a "seafood price premium" to create a fund to support monitoring systems and for damage compensation to producers in the presence of HABs. Results show that most economic studies on HAB valuation do not consider any cost-benefit analysis of a defined policy intervention. The predominant economic valuation methodology uses market information to estimate a proxy for welfare measure of the impact of HABs (loss revenue, sales, exports). Moreover, nonuse and indirect use values are ignored in the literature, while stated preference methodologies are underrepresented. Finally, results from 1293 surveys found that people are willing to pay an increase in the price of mussels to support a policy that informs on HAB. However, the lack of institutional trust affects the probability of paying negatively.
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Proliferação Nociva de Algas , Análise Custo-Benefício , Política Ambiental/economiaRESUMO
Numerous natural antioxidants have been developed into agents for neurodegenerative diseases (NDs) treatment. Rosmarinic acid (RA), an excellent antioxidant, exhibits neuroprotective activity, but its anti-NDs efficacy remains puzzling. Here, Caenorhabditis elegans models were employed to systematically reveal RA-mediated mechanisms in delaying NDs from diverse facets, including oxidative stress, the homeostasis of neural and protein, and mitochondrial disorders. Firstly, RA significantly inhibited reactive oxygen species accumulation, reduced peroxide malonaldehyde production, and strengthened the antioxidant defense system via increasing superoxide dismutase activity. Besides, RA reduced neuronal loss and ameliorated polyglutamine and É-synuclein-mediated dyskinesia in NDs models. Further, in combination with the data and molecular docking results, RA may bind specifically to Huntington protein and É-synuclein to prevent toxic protein aggregation and thus enhance proteostasis. Finally, RA ameliorated mitochondrial dysfunction including increasing adenosine triphosphate and mitochondrial membrane potential levels and rescuing mitochondrial membrane proteins' expressions and mitochondrial structural abnormalities via regulating mitochondrial dynamics genes and improving the mitochondrial kinetic homeostasis. Thus, this study systematically revealed the RA-mediated neuroprotective mechanism and promoted RA as a promising nutritional intervention strategy to prevent NDs.
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This article aims to provide theoretical predictions for the thermal reactions of human tissues during tumor thermotherapy when exposed to laser irradiation and an external heat source. For the construction of a theoretical study of bioheat transfer, the selection of a suitable thermal model capable of accurately predicting the required thermal responses is essential. The effect of heat production by heat treatment on a spherical multilayer tumor tissue is evaluated using this approach. Analytical solution for the non-homogenous differential equations is derived in the Laplace domain. The study examines the impact of thermal relaxation time on tissue temperature and the subsequent thermal damage. The numerical findings of thermal damage and temperatures are depicted in a graphical representation. This model explains laser treatment, physical events, metabolic support, and blood perfusion. The numerical outcomes of the recommended model are validated by comparing them to the literatures.
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This study reviews the latest progress on the research of electrical stimulationï¼ESï¼ in peripheral nerve regeneration, summarizes the parameters in preclinical experiments and discusses the effect on nerve regeneration. A detailed description is given in the study of conditioning electrical stimulation and nerve conduit scaffolding technology combined with ES, which have been hotly researched in recent years.
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Estimulação Elétrica , Regeneração Nervosa , Nervos Periféricos , Estimulação Elétrica/métodos , Nervos Periféricos/fisiologia , Animais , Traumatismos dos Nervos Periféricos/terapia , Humanos , Alicerces Teciduais , Terapia por Estimulação Elétrica/métodosRESUMO
Biological invasions are increasingly recognised as a major global change that erodes ecosystems, societal well-being, and economies. However, comprehensive analyses of their economic ramifications are missing for most national economies, despite rapidly escalating costs globally. Türkiye is highly vulnerable to biological invasions owing to its extensive transport network and trade connections as well as its unique transcontinental position at the interface of Europe and Asia. This study presents the first analysis of the reported economic costs caused by biological invasions in Türkiye. The InvaCost database which compiles invasive non-native species' monetary costs was used, complemented with cost searches specific to Türkiye, to describe the spatial and taxonomic attributes of costly invasive non-native species, the types of costs, and their temporal trends. The total economic cost attributed to invasive non-native species in Türkiye (from 202 cost reporting documents) amounted to US$ 4.1 billion from 1960 to 2022. However, cost data were only available for 87 out of 872 (10%) non-native species known for Türkiye. Costs were biased towards a few hyper-costly non-native taxa, such as jellyfish, stink bugs, and locusts. Among impacted sectors, agriculture bore the highest total cost, reaching US$ 2.85 billion, followed by the fishery sector with a total cost of US$ 1.20 billion. Management (i.e., control and eradication) costs were, against expectations, substantially higher than reported damage costs (US$ 2.89 billion vs. US$ 28.4 million). Yearly costs incurred by non-native species rose exponentially over time, reaching US$ 504 million per year in 2020-2022 and are predicted to increase further in the next 10 years. A large deficit of cost records compared to other countries was also shown, suggesting a larger monetary underestimate than is typically observed. These findings underscore the need for improved cost recording as well as preventative management strategies to reduce future post-invasion management costs and help inform decisions to manage the economic burdens posed by invasive non-native species. These insights further emphasise the crucial role of standardised data in accurately estimating the costs associated with invasive non-native species for prioritisation and communication purposes.
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Espécies Introduzidas , Ecossistema , Conservação dos Recursos Naturais/economia , Agricultura/economia , Animais , Pesqueiros/economiaRESUMO
BACKGROUND: Store-operated Ca2+ entry (SOCE) mediated by ORAI1 channel plays a crucial role in acute pancreatitis (AP). Macrophage is an important regulator in amplifying pancreatic tissue damage, but little is known about the role of ORAI1 in macrophages. In this study, we examined the effects of macrophage-specific ORAI1 on pancreatic tissue damage in AP. METHOD: Myeloid-specific Orai1 deficient mice was generated by crossing a LysM-Cre mouse line with Orai1f/f mice. Bone marrow-derived macrophages (BMDMs) were isolated, cultured, and stimulated to induce M1 or M2 macrophage polarization. Intracellular Ca2+ signals were measured by time-lapse confocal microscope imaging, with a Ca2+ indicator (Fluo 4). Experimental AP was induced by hourly intraperitoneal injections of caerulein or retrograde biliopancreatic infusion of sodium taurocholate. Pancreatic tissue damage was assessed by histopathological scoring and immunostaining. Sepsis was induced by intraperitoneal injection of lipopolysaccharide; organ damage and serum pro-inflammatory cytokines were measured. RESULT: Myeloid-specific Orai1 deletion exhibited minimal effect on SOCE in M0 macrophages and promoted M2 macrophage polarization ex vivo. Myeloid-specific Orai1 deletion did not affect pancreatic tissue damage, nor neutrophil or macrophage infiltration in two models of AP. Similarly, myeloid-specific Orai1 deletion did not influence overall survival rate in a model of sepsis, nor lung, kidney, and liver damage; while serum pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1ß were higher in Orai1ΔLysM mice, but were largely reduced in mice with Orai1 inhibitor. CONCLUSION: Our data suggest that ORAI1 may not be a predominant SOCE channel in macrophages and play a limited role in mediating pancreatic tissue damage in AP.
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Macrófagos , Proteína ORAI1 , Pâncreas , Pancreatite , Animais , Proteína ORAI1/metabolismo , Proteína ORAI1/genética , Pancreatite/patologia , Pancreatite/metabolismo , Pancreatite/induzido quimicamente , Pancreatite/genética , Camundongos , Macrófagos/metabolismo , Pâncreas/patologia , Pâncreas/metabolismo , Camundongos Endogâmicos C57BL , Células Mieloides/metabolismo , Camundongos Knockout , Modelos Animais de Doenças , Deleção de GenesRESUMO
Neuronal damage resulting from traumatic brain injury (TBI) causes disruption of neuronal projections and neurotransmission that contribute to behavioral deficits. Cellular generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is an early event following TBI. ROS often damage DNA, lipids, proteins, and carbohydrates while RNS attack proteins. The products of lipid peroxidation 4-hydroxynonenal (4-HNE) and protein nitration 3-nitrotyrosine (3-NT) are often used as indicators of oxidative and nitrosative damages, respectively. Increasing evidence has shown that striatum is vulnerable to damage from TBI with a disturbed dopamine neurotransmission. TBI results in neurodegeneration, oxidative stress, neuroinflammation, neuronal apoptosis, and autophagy in the striatum and contribute to motor or behavioral deficits. Pomalidomide (Pom) is a Food and Drug Administration (FDA)-approved immunomodulatory drug clinically used in treating multiple myeloma. We previously showed that Pom reduces neuroinflammation and neuronal death induced by TBI in rat cerebral cortex. Here, we further compared the effects of Pom in cortex and striatum focusing on neurodegeneration, oxidative and nitrosative damages, as well as neuroinflammation following TBI. Sprague-Dawley rats subjected to a controlled cortical impact were used as the animal model of TBI. Systemic administration of Pom (0.5 mg/kg, intravenous [i.v.]) at 5 h post-injury alleviated motor behavioral deficits, contusion volume at 24 h after TBI. Pom alleviated TBI-induced neurodegeneration stained by Fluoro-Jade C in both cortex and striatum. Notably, Pom treatment reduces oxidative and nitrosative damages in cortex and striatum and is more efficacious in striatum (93% reduction in 4-HNE-positive and 84% reduction in 3-NT-positive neurons) than in cerebral cortex (42% reduction in 4-HNE-positive and 55% reduction in 3-NT-positive neurons). In addition, Pom attenuated microgliosis, astrogliosis, and elevations of proinflammatory cytokines in cortical and striatal tissue. We conclude that Pom may contribute to improved motor behavioral outcomes after TBI through targeting oxidative/nitrosative damages and neuroinflammation.
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Lesões Encefálicas Traumáticas , Doenças Neuroinflamatórias , Talidomida/análogos & derivados , Ratos , Animais , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Estresse Oxidativo , Citocinas/metabolismo , Córtex Cerebral/metabolismo , Modelos Animais de DoençasRESUMO
Insulin-mechanistic target of rapamycin (mTOR) signaling drives anabolic growth during organismal development; its late-life dysregulation contributes to aging and limits lifespans. Age-related regulatory mechanisms and functional consequences of insulin-mTOR remain incompletely understood. Here, we identify LPD-3 as a megaprotein that orchestrates the tempo of insulin-mTOR signaling during C. elegans aging. We find that an agonist insulin, INS-7, is drastically overproduced from early life and shortens lifespan in lpd-3 mutants. LPD-3 forms a bridge-like tunnel megaprotein to facilitate non-vesicular cellular lipid trafficking. Lipidomic profiling reveals increased hexaceramide species in lpd-3 mutants, accompanied by up-regulation of hexaceramide biosynthetic enzymes, including HYL-1. Reducing the abundance of HYL-1, insulin receptor/DAF-2 or mTOR/LET-363, normalizes INS-7 levels and rescues the lifespan of lpd-3 mutants. LPD-3 antagonizes SINH-1, a key mTORC2 component, and decreases expression with age. We propose that LPD-3 acts as a megaprotein brake for organismal aging and that its age-dependent decline restricts lifespan through the sphingolipid-hexaceramide and insulin-mTOR pathways.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Envelhecimento , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Insulina/metabolismo , Longevidade/fisiologia , Serina-Treonina Quinases TOR/metabolismoRESUMO
The present investigation dealt with harmful effects of hexavalent chromium (Cr [VI]) on liver of Swiss albino mice. This variant exhibited cytotoxicity, mutagenicity, and carcinogenicity. Our study focused on elucidating the hepatotoxic effects of chronic low-dose exposure to Cr (VI) (2, 5, and 10 ppm) administered via drinking water for 4 and 8 months. The observed elevation in SGPT, ALP, and SGOT and increased oxidative stress markers unequivocally confirmed the severe disruption of liver homeostasis at these low treatment doses. Noteworthy alterations in histoarchitecture, body weight, and water intake provided further evidences of the harmful effects of Cr (VI). Production of reactive oxygen species (ROS) during metabolism led to DNA damages. Immunohistochemistry and qRT-PCR analyses revealed that chronic low-dose exposure of Cr (VI) induced apoptosis in liver tissue. Our study exhibited alterations in the expression pattern of DNA repair genes (Rad51, Mutyh, Mlh1, and Ogg1), coupled with promoter hypermethylation of Mutyh and Rad51, leading to transcriptional inhibition. Our findings underscored the potential of low-dose Cr (VI) exposure on hepatotoxicity by the intricate interplay between apoptosis induction and epigenetic alterations of DNA repair genes.
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Apoptose , Cromo , Metilação de DNA , Reparo do DNA , Fígado , Estresse Oxidativo , Regiões Promotoras Genéticas , Animais , Cromo/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Camundongos , Apoptose/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Regiões Promotoras Genéticas/efeitos dos fármacos , Masculino , Espécies Reativas de Oxigênio/metabolismo , DNA Glicosilases/genética , Relação Dose-Resposta a Droga , Dano ao DNA/efeitos dos fármacos , Rad51 Recombinase/genéticaRESUMO
Cyanobacterium Nostoc commune has long been used to alleviate various diseases. This research examines the effects of Nostoc commune extract (NCE) against behavioral disorders, cerebral oxidative stress, and inflammatory damage in the ketamine-induced schizophrenia model. Oral NCE administration (70 and 150 mg/kg/d) is performed after intraperitoneal ketamine injection (20 mg/kg) for 14 consecutive days. The forced swimming and open field tests are used to assess schizophrenia-like behaviors. After the behavioral test, dopamine (DA) level, oxidative stress markers, as well as the interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expression are measured in the cerebral cortex. The results show that NCE treatment ameliorates KET-induced anxiety and depressive-like behaviors in OFT and FST, respectively. NCE considerably decreases the malondialdehyde (MDA) and DA levels and IL-6 and TNF-α expressions in mice with schizophrenia-like symptoms. Also, a significant increase is observed in the glutathione (GSH) level and catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GRx) activity in cerebral tissue. The present study shows that NCE treatment effectively improves KET-induced schizophrenia-like behaviors and oxidative and inflammatory damage. Therefore, NCE, via its bioactive constituents, could have strong neuroprotective effects in the schizophrenia-like model.
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The adverse environmental impacts on mangrove ecosystems due to anthropogenic marine debris contamination have attracted public attention not only in Sri Lanka but worldwide. Therefore, quantification of marine debris in sensitive ecosystems like mangroves is critical to assess the impacts on ecosystem vitality and services. We conducted this study to assess the abundance and density of marine debris in Negombo lagoon, Western Province, Sri Lanka. We selected two sites (n = 2) using the purposive sampling technique. Marine debris cover and concentration were calculated to explore the extent of pollution from marine debris. The findings revealed that 9.83 ± 1.05 % of the substrate of the mangrove ecosystem is covered by debris. Nine types of marine debris were recorded, and a higher abundance belonged to single-use plastic items. A significantly higher debris cover was found in Kadolkele (18.80 ± 1.74 %, n = 120) than in Molekadolwetiya (0.85 ± 0.03 %, n = 120) (One-way ANOVA, p < 0.05). The study indicated that the mangroves in lagoon are highly polluted with marine debris and act as "litter catchers." Correlation coefficient analysis was used to find the impact of debris cover on physical damage to roots, seedlings, and undergrowth vegetation. Correlation analysis revealed that physical damage to seedlings and branches/barks have a positive correlation with debris cover. To conserve these valuable coastal habitats in Negombo lagoon, it is recommended to take remedial measures to reduce arriving debris loads and to remove the debris present in mangroves.
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Ecossistema , Poluição Ambiental , Sri Lanka , Poluição Ambiental/análise , Plásticos/análise , Monitoramento AmbientalRESUMO
Telomeres are located at the ends of linear chromosomes and play a critical role in maintaining genomic stability by preventing premature activation of DNA repair mechanisms. Because of exposure to various genotoxic agents, telomeres can undergo shortening and genetic changes. In mammalian cells, the basic DNA repair mechanisms, including base excision repair, nucleotide excision repair, double-strand break repair, and mismatch repair, function in repairing potential damages in telomeres. If these damages are not repaired correctly in time, the unfavorable results such as apoptosis, cell cycle arrest, and cancerous transition may occur. During lifespan, mammalian somatic cells, male and female germ cells, and preimplantation embryos experience a number of telomeric damages. Herein, we comprehensively reviewed the crosstalk between telomeres and the DNA repair mechanisms in the somatic cells, germ cells, and embryos. Infertility development resulting from possible defects in this crosstalk is also discussed in the light of existing studies.