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1.
Expert Rev Mol Med ; 26: e16, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557638

RESUMO

Epigenetic modifications, such as DNA methylation, are enzymatically regulated processes that directly impact gene expression patterns. In early life, they are central to developmental programming and have also been implicated in regulating inflammatory responses. Research into the role of epigenetics in neonatal health is limited, but there is a growing body of literature related to the role of DNA methylation patterns and diseases of prematurity, such as the intestinal disease necrotizing enterocolitis (NEC). NEC is a severe intestinal inflammatory disease, but the key factors that precede disease development remain to be determined. This knowledge gap has led to a failure to design effective targeted therapies and identify specific biomarkers of disease. Recent literature has identified altered DNA methylation patterns in the stool and intestinal tissue of neonates with NEC. These findings provide the foundation for a new avenue in NEC research. In this review, we will provide a general overview of DNA methylation and then specifically discuss the recent literature related to methylation patterns in neonates with NEC. We will also discuss how DNA methylation is used as a biomarker for other disease states and how, with further research, methylation patterns may serve as potential biomarkers for NEC.


Assuntos
Metilação de DNA , Enterocolite Necrosante , Animais , Humanos , Biomarcadores , Enterocolite Necrosante/genética , Enterocolite Necrosante/metabolismo , Epigênese Genética
2.
Mol Carcinog ; 63(5): 817-833, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38299738

RESUMO

Chronic exposure to arsenic (As) promotes skin carcinogenesis in humans and potentially disturbs resident stem cell dynamics, particularly during maternal and early life exposure. In the present study, we demonstrate how only prenatal arsenic exposure disturbs keratinocyte stem cell (KSC) conditioning using a BALB/c mice model. Prenatal As exposure alters the normal stemness (CD34, KRT5), differentiation (Involucrin), and proliferation (PCNA) program in skin of offspring with progression of age as observed at 2, 10, and 18 weeks. Primary KSCs isolated from exposed animal at Day-2 showed increased survival (Bax:Bcl-xL, TUNEL assay), proliferation (BrdU), and differentiation (KRT5, Involucrin) potential through the activation of pro-carcinogenic IGF2R-MAPK cascade (IGF2R-G(α)q-MEK1-ERK1/2). This was associated with reduced enrichment of histone H3K27me3 and its methylase, EZH2 along with increased binding of demethylase, KDM6A at Igf2r promoter. Altered KSCs conditioning through disturbed Igf2r imprint contributed to impaired proliferation and differentiation and an aggravated tumor response in offspring.


Assuntos
Arsênio , Queratinócitos , Neoplasias Cutâneas , Animais , Feminino , Camundongos , Gravidez , Arsênio/toxicidade , Carcinogênese/efeitos dos fármacos , Carcinogênese/metabolismo , Carcinogênese/patologia , Queratinócitos/metabolismo , Queratinócitos/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células-Tronco/metabolismo , Células-Tronco/patologia , Receptor IGF Tipo 2/efeitos dos fármacos , Receptor IGF Tipo 2/metabolismo , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
3.
J Contemp Dent Pract ; 25(2): 156-159, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38514413

RESUMO

AIM: The purpose of the present study was to evaluate the smear layer removal efficacy of three various agents on periodontally compromised tooth. MATERIALS AND METHODS: The current study included 75 molar teeth that were extracted due to periodontal disease. After that, 25 samples were randomly assigned using a simple random technique to the three different agent groups, group A: Scaling and root planing (SRP) and application of SofScale agent, group B: SRP and application of QMix agent, group C: SRP and application of MTAD agent. Using a diamond circular saw, the treated portions were divided into horizontal and vertical halves. All samples were viewed under Scanning Electron Microscope. Every tooth was focused at the coronal third, middle third, and apical third portion with a magnification of 1000×. Data were recorded and statistically analyzed. RESULTS: The smear layer removal efficacy was more in the QMix agent (3.06 ± 0.04) group followed by MTAD agent (3.28 ± 0.09) and SofScale agent (4.14 ± 0.10) group on the root surface. On intra group comparison, there was a statistically significant difference found in all the intra group agents with all the three levels. On inter group evaluation, at coronal third, there was no significant difference found between the different agents. There was a significant difference found between the different agents at middle and coronal third. CONCLUSION: On conclusion, the current investigation found that, the root surfaces treated with QMix shown a greater ability to remove smear layers compared to tooth surfaces treated with MTAD and SofScale agent. CLINICAL SIGNIFICANCE: Conventional therapies such as SRP effectively eliminate calculus, plaque, and necrosed cementum; nevertheless, they leave behind a smear layer that could impede normal healing. In an effort to overcome this, root conditioning agents were applied on the root surface to remove the smear layer. The traditional root conditioning agents such as citric acid have certain disadvantages, though, such as an acidic pH that could harm the root surface. As a result, researchers have been looking for biocompatible root conditioning treatments that are more effective. How to cite this article: Singh DK, BS Raj H, Soans CR, et al. Assessment of the Smear Layer Removal Efficacy of Three Different Agents on Periodontally Compromised Tooth: An In Vitro Study. J Contemp Dent Pract 2024;25(2):156-159.


Assuntos
Doenças Periodontais , Camada de Esfregaço , Humanos , Aplainamento Radicular , Raiz Dentária , Raspagem Dentária , Doenças Periodontais/tratamento farmacológico , Microscopia Eletrônica de Varredura , Ácido Edético/uso terapêutico
4.
J Contemp Dent Pract ; 25(1): 68-71, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38514434

RESUMO

AIM: The aim of the present study was to assess the stain removal ability and color stability of three distinct dentifrices on artificially stained enamel surface. MATERIALS AND METHODS: This study included 75 intact, healthy premolars free of dental caries that were extracted during orthodontic therapy. The samples were allowed to dry for 6 hours after being submerged in the prepared tea solution for roughly 18 hours every day. Then this procedure was repeated for seven successive days. All samples were randomly divided into three experimental groups with 25 samples in each group. Group I: control dentifrice, group II: dentifrice containing hydrogen peroxide, group III: dentifrice containing papain and bromelain. A specially designed toothbrushing simulator was used to brush every sample in the relevant group. Using a spectrophotometer and a measurement program, color measurement was evaluated after staining process after 4 weeks and 8 weeks of teeth cleaning. Using a profilometer, the surface roughness values (Ra) were assessed. RESULTS: After 8 weeks of brushing of stained samples, the color stability was better in dentifrice containing hydrogen peroxide (1.14 ± 0.11) followed by dentifrice containing papain and bromelain (1.22 ± 0.08) and control group (1.30 ± 0.09). And after 8 weeks of brushing of stained samples, the surface roughness was more in dentifrice containing hydrogen peroxide (0.237 ± 0.02) followed by dentifrice containing papain and bromelain (0.229 ± 0.13) and control group (0.207 ± 0.05). CONCLUSION: The present study concluded that the dentifrice containing hydrogen peroxide showed a superior whitening effect on the stained enamel surface than dentifrice containing papain and bromelain and control dentifrice. CLINICAL SIGNIFICANCE: The development of various dentifrice products has been greatly aided by the increased demand for an improved esthetic appearance. Teeth's natural color and any external stains that could accumulate on the tooth surface combine to determine a tooth's color. Additionally, the use of whitening dental pastes to remove external stains has grown in favor. With the development of these whitening toothpastes, dentifrices' ability to lessen or eliminate extrinsic dental stains has increased. How to cite this article: Mishra D, Kamath DG, Alagla M, et al. Evaluation of Stain Removal Efficacy and Color Stability of Three Different Dentifrices on Artificially Stained Enamel Surface-An In Vitro Study. J Contemp Dent Pract 2024;25(1):68-71.


Assuntos
Cárie Dentária , Dentifrícios , Clareamento Dental , Descoloração de Dente , Humanos , Dentifrícios/uso terapêutico , Bromelaínas/uso terapêutico , Peróxido de Hidrogênio/uso terapêutico , Corantes , Descoloração de Dente/tratamento farmacológico , Papaína/uso terapêutico , Cárie Dentária/tratamento farmacológico , Escovação Dentária , Esmalte Dentário
5.
Mol Pharm ; 20(9): 4714-4728, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37523676

RESUMO

This work focuses on developing nanoemulsions using a low-energy emulsification method for the codelivery of donepezil and memantine in one dosage form intended to be administered via the intranasal route for enhanced brain delivery. The nanoemulsion formulation was prepared using a low emulsification technique and characterized using various microscopy and nasal ciliotoxicity studies. The safe nanoemulsion was intended for preclinical pharmacokinetics with brain distribution and pharmacodynamics in a scopolamine-induced murine model. The formulated nanoemulsion was 16 nm in size, with a zeta potential of -7.22 mV, and exhibited a spherical shape. The brain concentration of IN-administered NE for DPZ and MEM was ∼678 and 249 ng/mL after 15 min. This concentration is more than 2 times higher in amount when compared with NE administered via PO, free drug solution administered via IN and PO route both. However, the plasma concentration of IN-administered NE for DPZ and MEM was ∼3 and 28 ng/mL after 15 min. In pharmacodynamic studies, the efficacy of NE administered via the IN route was higher when compared with other groups in neurobehavioral, biochemical estimation, and gene expression studies. The results suggest that the IN route can be explored in the future for the delivery of actives via nanocolloidal carriers in the brain for neurological disorders and can serve as promising alternatives for conventional dosage forms and routes.


Assuntos
Memantina , Nanopartículas , Camundongos , Animais , Donepezila , Administração Intranasal , Encéfalo/metabolismo , Escopolamina , Emulsões/metabolismo , Nanopartículas/química , Tamanho da Partícula
6.
Mol Biol Rep ; 50(2): 1033-1044, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36383337

RESUMO

BACKGROUND: Inorganic arsenic [As(III)] and hexavalent chromium [Cr(VI)] can potentially affect metabolic functions. These heavy metal(s)/metalloids can also affect the gut microbial architecture which affects metabolic health. Here, we assessed the effects of short-term exposure of As(III) and Cr(VI) on key transcription factors in adipose tissues and on selected gut microbial abundances to understand the possible modulatory role of these toxicants on host metabolic health. METHODS AND RESULTS: qRT-PCR based relative bacterial abundance studies in cecal samples, gene expression analysis for gut wall integrity in ileum and colon and adipogenesis, lipolysis, and thermogenic genes in gonadal white and brown adipose tissue (gWAT and BAT), along with tissue oxidative stress parameters have been performed. As(III) and Cr(VI) exposure reduced beneficial Lactobacilli, Bifidobacteria, Akkermansia, Lachenospiraceae, Fecalibacterium, Eubacterium, and clostridium coccoid group while increasing lipopolysaccharides producing Enterobacteriaceae abundances. It also impaired structural features and expression of key tight junction and mucin production genes in ileum and colon (Cld-2, Cld-4, ZO-1, ZO-2, MUC-2 and - 4). In gWAT it inhibited adipogenesis (PPARγ, FASN, SREBP1a), lipolysis (HSL, ACOX-1), and thermogenesis (UCP-1, PGC1a, PRDM-16, PPARa) related genes expression, whereas in BAT, it enhanced adipogenesis and reduced thermogenesis. These exposures also reduces the endogenous antioxidants levels in these tissues and promote pro-inflammatory cytokines genes expression (TLRs, IL-6, MCP-1). The combinatorial exposure appears to have more deleterious effects. CONCLUSION: These effects of As(III) and Cr(VI) may not directly be linked to their known toxicological effects, instead, more intriguing crosstalk with gut microbial ecosystem hold the key.


Assuntos
Arsênio , Camundongos , Animais , Arsênio/metabolismo , Ecossistema , Disbiose/metabolismo , Cromo/toxicidade , Cromo/metabolismo , Tecido Adiposo Branco/metabolismo , Termogênese
7.
Phys Chem Chem Phys ; 25(25): 16712-16717, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37338042

RESUMO

The vibrationally structured 3pz Rydberg excitation is identified and assigned in the VUV absorption spectrum of fenchone with an origin at 6.31 eV, below the prominent 6.4 eV C̃ (nominally 3p) band onset. This feature cannot, however, be observed in (2+1) REMPI spectra, as its relative excitation cross-section is much reduced in a two-photon transition. The 3py and 3px excitation thresholds, found to differ by only 10-30 meV, lie around 6.4 eV corresponding to the first intense C̃ band peak in both VUV and REMPI spectra. Calculations of vertical and adiabatic Rydberg excitation energies, photon absorption cross-sections, and vibrational profiles are used to support these interpretations.

8.
J Biochem Mol Toxicol ; 37(4): e23292, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36527247

RESUMO

Bisphenol A (BPA) is an omnipresent environmental pollutant. Despite being restrictions in-force for its utilization, it is widely being used in the production of polycarbonate plastics and epoxy resins. Direct, low-dose, and long-term exposure to BPA is expected when they are used in the packaging of food products and are used as containers for food consumption. Occupationally, workers are typically exposed to BPA at higher levels and for longer periods during the manufacturing process. BPA is a known endocrine disruptor chemical (EDC), that causes male infertility, which has a negative impact on human life from emotional, physical, and societal standpoints. To minimize the use of BPA in numerous consumer products, efforts and regulations are being made. Despite legislative limits in numerous nations, BPA is still found in consumer products. This paper examines BPA's overall male reproductive toxicity, including its impact on the hypothalamic-pituitary-testicular (HPT) axis, hormonal homeostasis, testicular steroidogenesis, sperm parameters, reproductive organs, and antioxidant defense system. Furthermore, this paper highlighted the role of non-monotonic dose-response (NMDR) in BPA exposure, which will help to improve the overall understanding of the harmful effects of BPA on the male reproductive system.


Assuntos
Disruptores Endócrinos , Masculino , Humanos , Disruptores Endócrinos/toxicidade , Sêmen , Genitália Masculina , Testículo , Compostos Benzidrílicos/toxicidade
9.
Med Vet Entomol ; 37(2): 209-212, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35822871

RESUMO

There are at least three known knockdown resistance (kdr) mutations reported globally in the human head louse Pediculus humanus capitis De Geer (Phthiraptera: Anoplura) that are associated with reduced sensitivity to pyrethroids. However, the prevalence of kdr mutation in head lice is not known in the Indian subcontinent. To identify kdr mutations in the Indian head lice population, the genomic region of the voltage-gated sodium channel gene encompassing IIS1-2 linker to IIS6 segments was PCR-amplified and sequenced from P. humanus capitis samples collected from different geographic localities of India. DNA sequencing revealed the presence of four kdr mutations: M827I, T929I, L932F and L1014F. The presence of a classical kdr mutation L1014F, the most widely reported mutation across insect-taxa associated with the kdr-trait, is being reported for the first time in P. humanus capitis.


Assuntos
Inseticidas , Infestações por Piolhos , Pediculus , Piretrinas , Humanos , Animais , Pediculus/genética , Resistência a Inseticidas/genética , Infestações por Piolhos/veterinária , Mutação , Inseticidas/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética
10.
Anim Biotechnol ; 34(2): 375-383, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34487479

RESUMO

Brucellosis is a widely prevalent zoonotic disease of major public health significance. A collection of Brucella melitensis and Brucella abortus field isolates of animal and human origin were subjected to MLVA-15 typing followed by phylogeography studies. The MLVA-15 analysis of B. melitensis (n = 65) field isolates resulted in 48 different profiles. The panel I marker bruce45 was found to be most conserved, while the rest of the panel I markers showed low to moderate length polymorphism. Among the panel II markers, bruce04, bruce16 and bruce30 showed a high discriminatory index. The MLVA-15 typing of 13 B. abortus field isolates revealed 13 different genotypes with panel II markers showing higher discriminatory ability vis-à-vis panel I. The minimum spanning tree analysis (MST) in comparison with isolates from the international database revealed that all B. melitensis and B. abortus isolates from this study belonged to the 'Eastern Mediterranean' and the 'abortus C' lineage, respectively. The MLVA-15 typing could differentiate field isolates of B. abortus and B. melitensis originating from different regions, reaffirming the technique's potential of high resolution and suitability for local epidemiological studies. The MLVA scheme also has the advantage of comparison of local isolates with a worldwide database, allowing for phylogeographical studies.


Assuntos
Brucella melitensis , Humanos , Animais , Brucella melitensis/genética , Filogenia , Tipagem de Sequências Multilocus , Repetições Minissatélites , Índia
11.
Int J Mol Sci ; 24(22)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38003466

RESUMO

The continuum of antioxidant response dysregulation in aging/oxidative stress-driven Nlrp3 inflammasome activation-mediated inflammatory response is associated with age-related diseases. Peroxiredoxin (Prdx) 6 is a key antioxidant that provides cytoprotection by regulating redox homeostasis. Herein, using lens epithelial cells (LECs) derived from the targeted inactivation of Prdx6 gene and aging lenses, we present molecular evidence that Prdx6-deficiency causes oxidative-driven Nlrp3 inflammasome activation, resulting in pyroptosis in aging/redox active cells wherein Prdx6 availability offsets the inflammatory process. We observed that Prdx6-/- and aging LECs harboring accumulated reactive oxygen species (ROS) showed augmented activation of Nlrp3 and bioactive inflammatory components, like Caspase-1, IL-1ß, ASC and Gasdermin-D. Similar to lipopolysaccharide treatment, oxidative exposure led to further ROS amplification with increased activation of the Nlrp3 inflammasome pathway. Mechanistically, we found that oxidative stress enhanced Kruppel-like factor 9 (Klf9) expression in aging/Prdx6-/- mLECs, leading to a Klf9-dependent increase in Nlrp3 transcription, while the elimination of ROS by the delivery of Prdx6 or by silencing Klf9 prevented the inflammatory response. Altogether, our data identify the biological significance of Prdx6 as an intrinsic checkpoint for regulating the cellular health of aging or redox active LECs and provide opportunities to develop antioxidant-based therapeutic(s) to prevent oxidative/aging-related diseases linked to aberrant Nlrp3 inflammasome activation.


Assuntos
Antioxidantes , Inflamassomos , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/metabolismo , Inflamassomos/metabolismo , Estresse Oxidativo , Peroxirredoxina VI/genética , Peroxirredoxina VI/metabolismo , Células Epiteliais/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
12.
J Contemp Dent Pract ; 24(8): 556-559, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38193177

RESUMO

AIM: The purpose of the current study was to evaluate the impact of three different denture cleansers on the strength and surface roughness of heat-polymerizing resin. MATERIALS AND METHODS: A total of 120 resin discs (10 mm in diameter and 2 mm thick) were created using a stainless steel mold for surface roughness testing and flexural strength testing (in accordance with the American Dental Association (ADA) Specification No.12). Samples were divided into one of three groups (40 samples in each group): group I: Clanden, group II: Clinsodent, group III: Fittydent. Samples were immersed in denture-cleansing solutions for 30 minutes every day, and this process was repeated over a period of 15 days. Samples were stored in distilled water at room temperature in between the immersions. A surface analyzer was utilized to compare the surface roughness of each sample before and after immersion treatments. For recording flexural strength, each sample was subjected to three-point bending test by mounting samples on Universal testing machine. Comparing mean values between groups using one-way ANOVA and the Tukeys honest significant difference (HSD) post hoc test. A significance level of 0.05 was used for all statistical calculations Results: After 15 days, the maximum change of mean surface roughness of heat-polymerizing resin was found in Clanden denture cleanser group (2.64 ± 0.12) followed by Clinsodent group (2.26 ± 0.09) and Fittydent group (1.92 ± 0.06). After 15 days, the maximum change of mean flexural strength changes of heat-polymerizing resin was found in Clanden denture cleanser group (94.78 ± 0.14), followed by Fittydent group (98.64 ± 0.03) and Clinsodent group (99.26 ± 0.21). CONCLUSION: Within the limitation, the current study concluded that changes were observed in surface roughness and flexural strength of all heat-polymerizing resin samples after immersion in all three denture cleansers; but least surface roughness and flexural strength changes were observed with the Fittydent cleanser group and Clinsodent group, respectively. CLINICAL SIGNIFICANCE: Cleaning dentures is crucial for maintaining both the prosthesis and oral health; therefore, it is necessary to select a cleanser that is effective without negatively affecting the base resin's qualities over time.


Assuntos
Higienizadores de Dentadura , Temperatura Alta , Estados Unidos , Higienizadores de Dentadura/farmacologia , Projetos de Pesquisa , Análise de Variância
13.
J Contemp Dent Pract ; 24(10): 739-742, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38152905

RESUMO

AIM: The purpose of the current study was to evaluate the impact of three various mouthwashes on the effectiveness of fluoride dentifrices in preventing enamel erosion. MATERIALS AND METHODS: A total of 120 sound intact human premolar teeth which were extracted for orthodontic treatment were selected for the study. A 3 × 3 mm window section was positioned in the middle of the coronal surface of the tooth in order to define the study area. Each sample was placed in a solution of 1% citric acid (pH 3.5) for 10 minutes in order to produce an eroded surface. All samples were divided into two main groups (60 samples each) as follows: Group A for sodium fluoride dentifrices and group B for stannous fluoride dentifrices, again it is subdivided into: CHX: Chlohex ADS®, EO: Listerine®, CPC: Colgate® Plax (20 samples in each subgroup). After that, samples underwent the pH cycling model for 5 days. Samples were examined for surface loss using a scanning electron microscope. RESULTS: In sodium fluoride dentifrices group, before intervention, the surface loss was 3.12 ± 1.03 in CHX group, 3.08 ± 1.20 in EO group, and 3.09 ± 0.96 in CPC group. After intervention, the less surface loss found with CHX group (2.18 ± 0.84), followed by CPC (2.34 ± 0.74) and EO group (2.46 ± 0.97). In stannous fluoride dentifrices group, before intervention, the surface loss in CHX group was 3.26 ± 1.19, in EO group, it was 3.18 ± 1.31, and in CPC group, it was 3.22 ± 1.06. After intervention, the less surface loss found with CHX: group (1.90 ± 0.54), followed by CPC (2.24 ± 0.28) and EO group (2.38 ± 0.20). CONCLUSION: The present study concluded that the fluoride dentifrices' preventive effects against tooth surface loss were unaffected by a different mouthwashes with varying compositions and major constituents. In terms of erosion, fluoridated toothpaste containing stannous fluoride was found to provide better surface loss protection than sodium fluoride. CLINICAL SIGNIFICANCE: Primary prevention and the eradication of contributing causes are the greatest strategies for preventing erosion. Simultaneously, antibacterial agent in the mouthwashes may help in enhancing the effect of fluoride in the enamel, owing to their high affinity for teeth structures. Therefore, in addition to cause-related treatment, further efforts to reduce tooth tissue loss are also necessary.


Assuntos
Dentifrícios , Doenças Dentárias , Erosão Dentária , Humanos , Fluoretos/uso terapêutico , Fluoreto de Sódio/farmacologia , Fluoreto de Sódio/uso terapêutico , Antissépticos Bucais/farmacologia , Antissépticos Bucais/uso terapêutico , Dentifrícios/uso terapêutico , Dentifrícios/química , Fluoretos de Estanho/farmacologia , Fluoretos de Estanho/uso terapêutico , Erosão Dentária/prevenção & controle , Esmalte Dentário
14.
Toxicol Appl Pharmacol ; 443: 116004, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35364107

RESUMO

Prenatal and postnatal life stress could be a potent programmer of phenotype or disease state of an individual in the later life. Prenatal arsenic exposure has been shown to promote developmental defects, low birth weight, immunotoxicity and is associated with various cancers including skin cancer in adulthood. To investigate the association between prenatal arsenic exposure and adult life skin carcinogenesis, we used a two-stage cutaneous carcinogenesis model in which BALB/c mice were prenatally exposed to 0.04 mg/kg and 0.4 mg/kg arsenic (As). Exposure to arsenic was sufficient to shorten the tumor latency period and promote epidermal hyperplasia in the offspring upon challenge with dimethylbenz[a]/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA). The levels of inflammatory and tissue microenvironment remodeling factors such as IL-1α and TNF-α were persistently elevated in the skin, and their inhibition through diacerein led to a significant decrease in the tumor response, suggesting their role in tumorigenesis. While there was overexpression of multiple epigenetic regulators at tissue level, we found decreased enrichment of Polycomb repressive complex 2 (PRC2) member EZH2 and H3K27me3 mark at the upstream of the affected inflammatory genes. The higher expression of the inflammatory genes suggests the gene specific selective nature of EZH2 repression which was also associated with increased binding of the activator KDM6a (demethylase). Further, arsenic conditioned basal keratinocytes cells (BKCs) showed increased migration and proliferation along with higher expression of tumor associated cytokines. Inhibition of EZH2 in the BKCs lead to their further upregulation suggesting that BKCs might be the potential cell type for the interaction of EZH2 and inflammatory cytokines. The present study provides new evidence for the role of PRC2 group regulators in inflammatory conditioning and development of skin cancer in offspring prenatally exposed to arsenic.


Assuntos
Arsênio , Efeitos Tardios da Exposição Pré-Natal , Neoplasias Cutâneas , Adulto , Animais , Arsênio/toxicidade , Carcinogênese/induzido quimicamente , Carcinogênese/genética , Citocinas , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Feminino , Humanos , Inflamação/induzido quimicamente , Camundongos , Camundongos Endogâmicos BALB C , Complexo Repressor Polycomb 2/metabolismo , Gravidez , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Microambiente Tumoral
15.
Environ Res ; 213: 113689, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35718163

RESUMO

A preponderance of recent evidence indicates that oxybenzone and other personal-care product chemicals threaten the biota inhabiting various ecological niches. What is understudied is the ecotoxicological impact of oxybenzone, a UV filter in sunscreens and anti-aging products, to terrestrial/soil organisms that are keystone species in these habitats. In the present study, acute exposure (14-day) to oxybenzone resulted in earthworm mortality (LC50 of 364 mg/kg) and growth rate inhibition. Environmentally relevant concentration of oxybenzone (3.64, 7.28 and 36.4 mg/kg) at exposures of 7-day, 14-day, 28-day induced oxidative stress and neurotoxicity followed by perturbations in reproduction processes and changes in vital organs. Decreased levels of superoxide dismutase (SOD) and catalase (CAT) activity were statistically lower than controls (p < 0.05) on day 14 for all three concentrations, while glutathione-s-transferase (GST) activity was significantly elevated from controls on days 7 and 14. On day 28, SOD and CAT activities were either not significantly different from the control or were higher, demonstrating a temporal multiphasic response of anti-oxidant enzymes. GST activity on day 28 was significantly reduced compared to controls. Acetylcholinesterase levels across the three-time points exhibited a complicated behaviour, with every exposure concentration being significantly different from the control. Chronic exposure negatively influences earthworm health status with elevated biomarker values analysed using IBRv2 index. This, in turn, impacted higher levels of hierarchical organization, significantly impairing reproduction and organismal homeostasis at the histological level and manifesting as decreasing cocoon formation and successful hatching events. Thus, the overall findings demonstrate that oxybenzone is toxic to Eisenia fetida at low-level, long-term exposure. Based on the concentration verification analysis and application of the EPA PestDF tool, oxybenzone undergoes single first-order kinetics degradation in OECD soil with DT50 and DT90 as 8.7-28.9 days, respectively.


Assuntos
Oligoquetos , Poluentes do Solo , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/metabolismo , Benzofenonas , Catalase/metabolismo , Oligoquetos/metabolismo , Estresse Oxidativo , Solo/química , Poluentes do Solo/metabolismo , Poluentes do Solo/toxicidade , Superóxido Dismutase/metabolismo
16.
Toxicol Ind Health ; 38(3): 139-150, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35230206

RESUMO

Blood lead level (BLL) is the primary biomarker for lead-exposure monitoring in occupationally exposed workers. We evaluated occupational lead-exposure (OE) impact on cardiopulmonary functions in lead-acid battery recycling unit workers. Seventy-six OE cases and 30 control subjects were enrolled for questionnaire-based socio-demographic, dietary, tobacco usage, and medical history data. Anthropometric measurements, systolic and diastolic blood pressure (SBP and DBP), and pulmonary function tests were performed. Venous blood was collected for BLL, hematological analysis, and biochemical analysis. OE caused a significant increase in BLL, SBP, DBP, and small airways obstruction in lung function tests. It also impaired platelet indices, affected renal and liver biochemical measurements, and promoted oxidative stress and DNA damage. Multilinear regression analysis suggested that BLL affected SBP (ß = 0.314, p = .034) and increased small airways obstruction (FEV1/FVC, ß = -0.37, p = .05; FEV25-75%, ß = -0.351, p = .016). Higher BLL appears to be an independent modulator of hypertension and poor pulmonary function upon occupational lead exposure in lead-acid battery recyclers.


Assuntos
Hipertensão , Exposição Ocupacional , Pressão Sanguínea/fisiologia , Estudos Transversais , Humanos , Hipertensão/etiologia , Chumbo , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise
17.
Sensors (Basel) ; 22(16)2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36015996

RESUMO

The management of water resources is a priority problem in agriculture, especially in areas with a limited water supply. The determination of crop water requirements and crop coefficient (Kc) of agricultural crops helps to create an appropriate irrigation schedule for the effective management of irrigation water. A portable smart weighing lysimeter (1000 × 1000 mm and 600 mm depth) was developed at CPCT, IARI, New Delhi for real-time measurement of Crop Coefficient (Kc) and water requirement of chrysanthemum crop and bulk data storage. The paper discusses the assembly, structural and operational design of the portable smart weighting lysimeter. The performance characteristics of the developed lysimeter were evaluated under different load conditions. The Kc values of the chrysanthemum crop obtained from the lysimeter installed inside the greenhouse were Kc ini. 0.43 and 0.38, Kc mid-1.27 and 1.25, and Kc end-0.67 and 0.59 for the years 2019-2020 and 2020-2021, respectively, which apprehensively corroborated with the FAO 56 paper for determination of crop coefficient. The Kc values decreased progressively at the late-season stage because of the maturity and aging of the leaves. The lysimeter's edge temperature was somewhat higher, whereas the center temperature closely matched the field temperature. The temperature difference between the center and the edge increased as the ambient temperature rose. The developed smart lysimeter system has unique applications due to its real-time measurement, portable attribute, and ability to produce accurate results for determining crop water use and crop coefficient for greenhouse chrysanthemum crops.


Assuntos
Chrysanthemum , Transpiração Vegetal , Irrigação Agrícola/métodos , Agricultura , Produtos Agrícolas , Água
18.
Cancer Metastasis Rev ; 39(3): 989-998, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32519151

RESUMO

Lung cancer is one of the most common diseases among humans and one of the major causes of growing mortality. Medical experts believe that diagnosing lung cancer in the early phase can reduce death with the illustration of lung nodule through computed tomography (CT) screening. Examining the vast amount of CT images can reduce the risk. However, the CT scan images incorporate a tremendous amount of information about nodules, and with an increasing number of images make their accurate assessment very challenging tasks for radiologists. Recently, various methods are evolved based on handcraft and learned approach to assist radiologists. In this paper, we reviewed different promising approaches developed in the computer-aided diagnosis (CAD) system to detect and classify the nodule through the analysis of CT images to provide radiologists' assistance and present the comprehensive analysis of different methods.


Assuntos
Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/diagnóstico por imagem , Diagnóstico por Computador/métodos , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Tomografia Computadorizada por Raios X/métodos
19.
Biomed Microdevices ; 23(4): 56, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34705117

RESUMO

Non-invasive collection of biological sample such as sweat, urine, saliva, hairs and, stool and onsite detection of anlaytes in those samples is an interesting and viable approach for rapid screening of various toxicants in body. Environmental exposure/presence of lead (82Pb) and its rapid detection provide one such opportunity. A chemical spot based colorimetric method and a transdermal patch device based on this spot test, is developed for rapid and qualitative assessment of inorganic lead (Pb2+) in non-coloured biological or environmental liquid samples. The transdermal patch system contains two important parts, a chemical spot prepared on a thin glass sheet and, an absorbent paper (11 µm pore size). A one step colour development reaction is able to identify the presence or absence of Pb2+. In-vitro evaluation for sensitivity and cut-off value determination, within run and between run precision testing, specificity testing were done. In-vivo evaluation of the developed patch system was performed in occupationally lead-exposed subjects and in control volunteers. In-vivo field testing results were further validated with gold standard test for lead detection. Blood lead levels and patch lead levels were found to be positively correlated (r = 0.57, P < 0.0001). In addition, the sensitivity and specificity of device in identification of Pb2+ was found to be 75.93% (95% CI = 62.36%-86.51%) and 95.24% (95% CI = 76.18%-99.88%). The developed system appears as a reliable, non-invasive rapid test with minimum step involve for identification of Pb2+ in a given system.


Assuntos
Chumbo , Sistemas Automatizados de Assistência Junto ao Leito , Colorimetria , Humanos , Saliva , Sensibilidade e Especificidade
20.
Cell Biol Toxicol ; 37(4): 531-553, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33146789

RESUMO

Cigarette smoking is the chief etiological factor for chronic obstructive pulmonary disease (COPD). Oxidative stress induced by cigarette smoke (CS) causes protein degradation, DNA damage, and cell death, thereby resulting in acute lung injury (ALI). In this regard, autophagy plays a critical role in regulating inflammatory responses by maintaining protein and organelle homeostasis and cellular viability. Expression of autophagy-related proteins (ARPs) is regulated by the fork head box class O (FOXO) transcription factors. In the current study, we examined the role of FOXO family proteins-FOXO1 and FOXO3a-in regulating CS extract (CSE)-induced autophagy. Using human lung adenocarcinoma cells with type II alveolar epithelial characteristics (A549), we observed CSE-mediated downregulation of FOXO3a. In contrast, there was a pronounced increase in the expression of FOXO1 at both the transcriptional and translational levels in the CSE-challenged cells compared with controls. Interestingly, knockdown of FOXO3a heightened the CSE-mediated increase in expression of cytokines/chemokines (IL-6, IL-8, and MCP-1), ARPs, and the FOXO1 transcription factor. Moreover, FOXO1 knockdown rescued CSE-mediated upregulation of ARPs in A549 cells. In addition, using the ROS inhibitor N-acetyl-L-cysteine (NAC), we observed abrogated mRNA expression of several ARPs and production of inflammatory cytokines/chemokines (IL-6, IL-8, MCP-1, and CCL-5) in the CSE-challenged cells suggesting an important role of ROS in regulating CSE-induced autophagy. Chromatin immunoprecipitation of FOXO1 and FOXO3a demonstrated increased binding of the former to promoter regions of autophagy genes- BECLIN1, ATG5, ATG12, ATG16, and LC3 in CSE challenged cells. These findings suggest the role of FOXO1 in regulating the expression of these genes during CSE exposure. Overall, our findings provide evidence for FOXO3a-dependent FOXO1-mediated regulation of autophagy in the CSE-challenged cells. Graphical abstract.


Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Autofagia , Fumar Cigarros/efeitos adversos , Células Epiteliais , Humanos , Fumaça/efeitos adversos , Nicotiana , Fatores de Transcrição
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