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1.
J Eur Acad Dermatol Venereol ; 38(7): 1432-1438, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38483241

RESUMO

BACKGROUND: The detection of cutaneous metastases (CMs) from various primary tumours represents a diagnostic challenge. OBJECTIVES: Our aim was to evaluate the general characteristics and dermatoscopic features of CMs from different primary tumours. METHODS: Retrospective, multicentre, descriptive, cross-sectional study of biopsy-proven CMs. RESULTS: We included 583 patients (247 females, median age: 64 years, 25%-75% percentiles: 54-74 years) with 632 CMs, of which 52.2% (n = 330) were local, and 26.7% (n = 169) were distant. The most common primary tumours were melanomas (n = 474) and breast cancer (n = 59). Most non-melanoma CMs were non-pigmented (n = 151, 95.6%). Of 169 distant metastases, 54 (32.0%) appeared on the head and neck region. On dermatoscopy, pigmented melanoma metastases were frequently structureless blue (63.6%, n = 201), while amelanotic metastases were typified by linear serpentine vessels and a white structureless pattern. No significant difference was found between amelanotic melanoma metastases and CMs of other primary tumours. CONCLUSIONS: The head and neck area is a common site for distant CMs. Our study confirms that most pigmented melanoma metastasis are structureless blue on dermatoscopy and may mimic blue nevi. Amelanotic metastases are typified by linear serpentine vessels and a white structureless pattern, regardless of the primary tumour.


Assuntos
Dermoscopia , Melanoma , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico por imagem , Estudos Transversais , Pessoa de Meia-Idade , Feminino , Masculino , Estudos Retrospectivos , Idoso , Melanoma/patologia , Melanoma/secundário , Melanoma/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Adulto , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/secundário
2.
Int J Mol Sci ; 23(11)2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35682790

RESUMO

Diabetes mellitus is a frequent endocrine disorder characterized by hyperglycemia. Acrylamide (AA) is food contaminant formed during the high-temperature processing of food rich in carbohydrates and low in proteins. Recent human epidemiological studies have shown a potential association between AA exposure and the prevalence of diabetes in the general population. In male rats, AA treatment promoted pancreatic islet remodeling, which was determined by alpha-cell expansion and beta-cell reduction, while in female rats AA caused hyperglycemia and histopathological changes in pancreatic islets. In vitro and in vivo rodent model systems have revealed that AA induces oxidative stress in beta cells and that AA impairs glucose metabolism and the insulin signaling pathway. Animal studies have shown that diabetic rodents are more sensitive to acrylamide and that AA aggravates the diabetic state. In this review, we provide an overview of human epidemiological studies that examined the relation between AA exposure and glucose disorders. In addition, the effects of AA treatment on pancreatic islet structure, beta-cell function and glucose metabolism in animal models are comprehensively analyzed with an emphasis on sex-related responses. Furthermore, oxidative stress as a putative mechanism of AA-induced toxicity in beta cells is explored. Finally, we discuss the effects of AA on diabetics in a rodent model system.


Assuntos
Diabetes Mellitus , Hiperglicemia , Ilhotas Pancreáticas , Acrilamida/metabolismo , Acrilamida/toxicidade , Animais , Diabetes Mellitus/metabolismo , Feminino , Glucose/metabolismo , Humanos , Hiperglicemia/metabolismo , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Masculino , Ratos
3.
Int J Mol Sci ; 23(11)2022 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-35682741

RESUMO

Acrylamide (AA) toxicity is associated with oxidative stress. During detoxification, AA is either coupled to gluthatione or biotransformed to glycidamide by the enzyme cytochrome P450 2E1 (CYP2E1). The aim of our study was to examine the hepatotoxicity of AA in vivo and in vitro. Thirty male Wistar rats were treated with 25 or 50 mg/kg b.w. of AA for 3 weeks. Qualitative and quantitative immunohistochemical evaluation of inducible nitric oxide synthase (iNOS), CYP2E1, catalase (CAT), superoxide dismutase 1 (SOD1), and SOD2 expression in liver was carried out. Bearing in mind that the liver is consisted mainly of hepatocytes, in a parallel study, we used the rat hepatoma cell line H4IIE to investigate the effects of AA at IC20 and IC50 concentrations on the redox status and the activity of CAT, SOD, and glutathione-S-transferase (GST), their gene expression, and CYP2E1 and iNOS expression. Immunohistochemically stained liver sections showed that treatment with AA25mg induced a significant decrease of CYP2E1 protein expression (p < 0.05), while treatment with AA50mg led to a significant increase of iNOS protein expression (p < 0.05). AA treatment dose-dependently elevated SOD2 protein expression (p < 0.05), while SOD1 protein expression was significantly increased only at AA50mg (p < 0.05). CAT protein expression was not significantly affected by AA treatments (p > 0.05). In AA-treated H4IIE cells, a concentration-dependent significant increase in lipid peroxidation and nitrite levels was observed (p < 0.05), while GSH content and SOD activity significantly decreased in a concentration-dependent manner (p < 0.05). AA IC50 significantly enhanced GST activity (p < 0.05). The level of mRNA significantly increased in a concentration-dependent manner for iNOS, SOD2, and CAT in AA-treated H4IIE cells (p < 0.05). AA IC50 significantly increased the transcription of SOD1, GSTA2, and GSTP1 genes (p < 0.05), while AA IC20 significantly decreased mRNA for CYP2E1 in H4IIE cells (p < 0.05). Obtained results indicate that AA treatments, both in vivo and in vitro, change hepatocytes; drug-metabolizing potential and disturb its redox status.


Assuntos
Acrilamida , Citocromo P-450 CYP2E1 , Acrilamida/metabolismo , Acrilamida/toxicidade , Animais , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Glutationa Transferase/metabolismo , Hepatócitos/metabolismo , Peroxidação de Lipídeos , Masculino , Estresse Oxidativo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase-1/metabolismo
4.
Microsc Microanal ; 27(2): 437-449, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33586646

RESUMO

The aim of the present study was to determine and elaborate on all changes in old-aged (OA) versus young-aged (YA) rat thyroids by using stereological, ultrastructural, hormonal, and gene expression analyses. We used 4- and 24-month-old male Wistar rats in our evaluation, presenting all changes in comparison with YA rats. Results showed that the thyroid parenchyma was characterized by higher absolute volumes of the gland, colloid, epithelium, and interstitium by 135, 135, 140, and 142% (p < 0.05) respectively, while the relative volumes of colloid and glands were unchanged. Ultrastructural analysis revealed less active glands, with smaller amounts of lysosomes, thyroglobulin (Tg) granules, and microvilli in the luminal colloid. Optical density values for thyroid peroxidase (TPO), Tg, and vascular-endothelial growth factor immunostaining remained unchanged; however, TPO and Tg exhibited visually stronger expression in small active follicles. Thyroxine (T4)-Tg, the relative intensity of fluorescence (RIF), serum T4, and the sodium-iodide symporter immunohistochemical and gene expressions decreased by 20, 40, 29, and 31% (p < 0.05), respectively, in OA thyroids. Pituitary thyroid-stimulating hormone (TSH) RIF increased by 44% (p < 0.05), but the TSH serum concentration remained unchanged. In conclusion, the obtained results indicate depression of the thyroid gland synthetic and secretory capacity with advanced age.


Assuntos
Glândula Tireoide , Tireotropina , Animais , Expressão Gênica , Masculino , Ratos , Ratos Wistar , Tireoglobulina/genética
5.
Int Heart J ; 62(5): 1164-1170, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34544975

RESUMO

There is emerging evidence of prolonged recovery in survivors of coronavirus disease 2019 (COVID-19), even in those with mild COVID-19. In this paper, we report a case of a 39-year-old male with excessive body weight and a history of borderline values of arterial hypertension without therapy, who was mainly complaining of progressive dyspnea after being diagnosed with mild COVID-19. According to the recent guidelines on the holistic assessment and management of patients who had COVID-19, all preferred diagnostic procedures, including multidetector computed tomography (CT), CT pulmonary angiogram, and echocardiography, should be conducted. However, in our patient, no underlying cardiopulmonary disorder has been established. Therefore, considering all additional symptoms our patient had beyond dyspnea, our initial differential diagnosis included anxiety-related dysfunctional breathing. However, psychiatric evaluation revealed that our patient had only a mild anxiety level, which was unlikely to provoke somatic complaints. We decided to perform further investigations considering that cardiopulmonary exercise test (CPET) represents a reliable diagnostic tool for patients with unexplained dyspnea. Finally, the CPET elucidated the diastolic dysfunction of the left ventricle, which was the most probable cause of progressive dyspnea in our patient. We suggested that, based on uncontrolled cardiovascular risk factors our patient had, COVID-19 triggered a subclinical form of heart failure (HF) with preserved ejection fraction (HFpEF) to become clinically manifest. Recently, the new onset, exacerbation, or transition from subclinical to clinical HFpEF has been associated with COVID-19. Therefore, in addition to the present literature, our case should warn physicians on HFpEF among survivors of COVID-19.


Assuntos
COVID-19/complicações , Dispneia/diagnóstico , Dispneia/etiologia , Teste de Esforço , Adulto , Humanos , Masculino
6.
Phys Chem Chem Phys ; 22(24): 13721-13728, 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32529195

RESUMO

Stacking interactions between six-membered resonance-assisted hydrogen-bridged (RAHB) rings and C6-aromatic rings were systematically studied by analyzing crystal structures in the Cambridge Structural Database (CSD). The interaction energies were calculated by quantum-chemical methods. Although the interactions are stronger than benzene/benzene stacking interactions (-2.7 kcal mol-1), the strongest calculated RAHB/benzene stacking interaction (-3.7 kcal mol-1) is significantly weaker than the strongest calculated RAHB/RAHB stacking interaction (-4.7 kcal mol-1), but for a particular composition of RAHB rings, RAHB/benzene stacking interactions can be weaker or stronger than the corresponding RAHB/RAHB stacking interactions. They are also weaker than the strongest calculated stacking interaction between five-membered saturated hydrogen-bridged rings and benzene (-4.4 kcal mol-1) and between two five-membered saturated hydrogen-bridged rings (-4.9 kcal mol-1). SAPT energy decomposition analyses show that the strongest attractive term in RAHB/benzene stacking interactions is dispersion, however, it is mostly canceled by a repulsive exchange term; hence the geometries of the most stable structures are determined by an electrostatic term.

7.
Dermatol Ther ; 33(5): e13829, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32542964

RESUMO

For the last two decades, the outbreaks of diseases caused by coronaviruses and intermittent worldwide public health emergences have reminded us that they still represent a severe threat to global health. The recent outbreak of corona virus disease 19 (COVID-19) highlighted the urgent need for effective treatment, and initiated rapid search for therapies, able to counter the most severe disease effects. Many aspects of COVID-19 pathogenesis are unknown, but complex interplay of direct viral damage and immune response dysregulation is underline. Intensive research is undergoing for therapeutic targets of virus and high-efficiency and low toxicity targeted drugs. There is no available specific antiviral treatment of this disease, therefore repurposing of drugs already available for the treatment of other viral and autoimmune diseases has been a part of research efforts. Well known anti-inflammatory properties of chloroquine and hydroxychloroquine, agents widely used in dermatology, made them potential candidates for the treatment of COVID-19. We review pathogenesis and clinical characteristic of COVID-19, as well as treatment options that have been under evaluation in past several months. In addition, we focus more on chloroquine and hydroxychloroquine, their pharmacological properties, clinical utility, and current recommendations for their use in COVID-19.


Assuntos
Tratamento Farmacológico da COVID-19 , Dermatologia , Reposicionamento de Medicamentos , SARS-CoV-2 , Antivirais/uso terapêutico , COVID-19/complicações , Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico
8.
Dermatol Ther ; 33(3): e13285, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32105384

RESUMO

Annular lichenoid dermatitis of youth (ALDY), first described in 2003, represents an uncommon entity whose etiopathogenesis is still debated. Futhermore, the optimal treatment for ALDY is yet to be established. We report a 9-year-old girl who presented with annular and oval erythematous lesions mostly on her trunk, with several lesions on the neck, groin, flanks, and upper extremities. The lesions had histological and immunohistochemical features characteristic for ALDY. Treatment with H1-antihistamines, topical corticosteroid, and UVB therapy was unsuccessful, while systemic treatment with cyclosporine induced complete remission.


Assuntos
Erupções Liquenoides , Neurodermatite , Administração Cutânea , Adolescente , Criança , Ciclosporina/uso terapêutico , Feminino , Humanos , Erupções Liquenoides/induzido quimicamente , Erupções Liquenoides/diagnóstico , Erupções Liquenoides/tratamento farmacológico , Pele
9.
Exp Mol Pathol ; 100(3): 378-85, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27019369

RESUMO

p300 and p300/CBP-associated factor (PCAF) are histone modifiers and transcriptional co-factors involved in a number of cell processes. We investigated their expression patterns in 79 actinic keratoses (AK), 45 cases of Bowen's disease (BD), and 168 invasive squamous cell carcinomas of the skin (SCC). Using tissue microarray and immunohistochemistry, we evaluated p300 and PCAF expression in relation to the type of the lesion and SCC prognostic parameters (grade, diameter, thickness and level of invasion). High nuclear expression of p300 (>60% of positive cells) (p=0.001) and absent cytoplasmic expression (p=0.026) were more frequent in SCC compared to AK and BD, respectively. Cytoplasmic expression of p300 was associated with the SCC invasion of subcutaneous fat and deeper tissues (p=0.049). Diffuse distribution of cells with p300 nuclear expression was more commonly seen in BD and SCC compared to AK (p<0.001), in moderately- and poorly-differentiated SCC compared to well-differentiated SCC (p<0.001), in tumors thicker than 6mm (p<0.001), and in deeply invading tumors (p=0.001). More frequent loss of PCAF nuclear expression was observed in SCC than in AK and BD (p<0.001). Diffuse distribution of cells with PCAF cytoplasmic expression was more common in BD and SCC compared to AK (p<0.001), and in poorly-differentiated SCC compared to well- and moderately-differentiated SCC (p<0.001). Our results suggest that increase in nuclear expression of p300, as well as the presence of cytoplasmic but loss of nuclear expression of PCAF, could play an important role in the development and progression of cutaneous SCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteína p300 Associada a E1A/biossíntese , Ceratose Actínica/metabolismo , Neoplasias Cutâneas/metabolismo , Fatores de Transcrição de p300-CBP/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Pele/metabolismo , Pele/patologia , Análise Serial de Tecidos
10.
J Cutan Pathol ; 43(3): 200-10, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26349899

RESUMO

BACKGROUND: Actinic keratosis (AK) and Bowen's disease (squamous cell carcinoma in situ, SCCIS) are pre-invasive stages in the development of squamous cell carcinoma (SCC). METHODS: Immunohistochemical study of cyclin D1, cyclin E, p16(INK4a) and p21(Cip1) (/Waf1) in AK (53 cases), SCCIS (16 cases) and SCC (40 cases), in relation to the type of the lesion and SCC prognostic parameters (grade, diameter and thickness). RESULTS: Diffuse cyclin D1 distribution was more frequent in SCCIS and SCC than in AK (p = 0.03) and similar pattern was observed for p16(INK4a) . For cyclin E, central distribution dominated in SCC compared with the AK (p = 0.001) and SCCIS (p = 0.03). p21(Cip1) (/Waf1) displayed suprabasal distribution more frequently in AK than in SCCIS (p = 0.001) and SCC (p = 0.0004). Semiquantitative assessment showed more positive cells in AK (p = 0.04) and SCCIS (p = 0.04) than in SCC for cyclin E. SCC with diameter over 20 mm and those thicker than 6 mm revealed higher labeling index with p16(INK4a) and p21(Cip1) (/Waf1) , respectively. CONCLUSIONS: Our results suggest different alterations for p16(INK4a) and p21(Cip1) (/Waf1) in AK, SCCIS and SCC. Immunostaining distribution showed closer correlation with the type of the lesion, whereas percentage of positive cells displayed better association with the SCC prognostic parameters.


Assuntos
Carcinoma de Células Escamosas , Proteínas Inibidoras de Quinase Dependente de Ciclina/biossíntese , Ciclinas/biossíntese , Fase G1 , Regulação Neoplásica da Expressão Gênica , Ceratose Actínica , Proteínas de Neoplasias/biossíntese , Fase S , Neoplasias Cutâneas , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Ceratose Actínica/metabolismo , Ceratose Actínica/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
11.
Regul Toxicol Pharmacol ; 76: 94-101, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26828024

RESUMO

The aim of this study was to identify palatable additives which have a significant protective action against soft tissue changes in the oral cavity caused by Swedish smokeless tobacco ("snus"), and that satisfy existing legal requirements. Although the cancer risk from snus is extremely low, long term use may result in highly undesirable keratotic lesions and associated epithelial abnormalities in the oral cavity. The rat forestomach, which is vulnerable to the irritative action of non-genotoxic compounds like butylated hydroxyanisole, propionic acid as well as snus, was chosen as an experimental model. Studied toxicological endpoints included histopathology and cellular proliferation based on DNA incorporation of bromodeoxyuridine. After 6 weeks' exposure, blueberries (bilberries) and an extract from the common milk thistle were found to exert a highly significant inhibition of cell proliferation induced by snus in the rat forestomach epithelium, indicating a potential protection with respect soft tissue changes in the human oral cavity.


Assuntos
Mirtilos Azuis (Planta)/química , Proliferação de Células/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Silybum marianum/química , Silimarina/farmacologia , Estômago/efeitos dos fármacos , Tabaco sem Fumaça/toxicidade , Animais , Citoproteção , Replicação do DNA/efeitos dos fármacos , Frutas , Hiperplasia , Masculino , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Substâncias Protetoras/isolamento & purificação , Ratos Wistar , Silimarina/isolamento & purificação , Estômago/patologia , Fatores de Tempo
12.
J Dtsch Dermatol Ges ; 12(6): 467-72, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24825465

RESUMO

Amelanotic melanoma is a subtype of cutaneous melanoma without pigment. The clinical diagnosis is challenging because it may mimic benign or malignant melanocytic and non-melanocytic neoplasms and inflammatory skin diseases. In synchrony with the improvement of the diagnosis of pigmented lesions, dermatoscopy may assist the clinician in the diagnosis of non-pigmented skin neoplasms in general and of amelanotic melanoma in particular. We have searched the literature to extract the most relevant dermatoscopic clues to diagnose amelanotic and hypomelanotic melanomas by dermatoscopy. In addition we present eight consecutive cases and discuss their clinical and dermatoscopic characteristics in the light of published data.


Assuntos
Dermoscopia , Melanoma Amelanótico/diagnóstico , Melanoma Amelanótico/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Diagnóstico Diferencial , Humanos , Pele/patologia , Dermatopatias/diagnóstico , Dermatopatias/patologia
13.
Foods ; 13(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38928882

RESUMO

In the present study, the nutritional and sensory properties of spelt cookies without wild garlic, cookies with fresh wild garlic, cookies with osmodehydrated wild garlic in sugar beet molasses, and cookies with osmodehydrated wild garlic in an aqueous solution of sucrose and salt were evaluated and compared. The tested cookie samples were characterized in terms of total antioxidative activity, the total content of phenols, flavonoids, and thiosulfates, the presence of dominant phenols, the content of betaine and dietary fiber, antioxidant activity after in vitro digestion, and sensory attributes for appearance, taste, smell, and texture. The results proved that the addition of wild garlic leaves osmodehydrated in molasses provided the cookies with the best nutritional and bioactive properties: 1.75 times higher total phenols content, 2.4 times higher total flavonoids content, 1.52 times higher total thiosulfates content, and 1.56 times higher betaine content, and a total quality increase of 54% compared to the control cookies. The cookies enriched with osmodehydrated wild garlic in molasses were rated as pleasant and acceptable, but also more complex compared to other cookies. The production of this nutritionally and sensory-improved cookie would contribute to expanding the assortment of flour confectionery products, especially for consumers who care about health and nutrition.

14.
Foods ; 13(17)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39272478

RESUMO

Combined drying, an energy-efficient method that includes osmotic pretreatment in molasses and shortened successive lyophilization, was used to obtain celery root powder and incorporate it in the formulation of cookies, with the aim of obtaining a new product. Wheat flour was substituted with combinedly dehydrated celery root powder at levels from 0 to 30%, and optimization of the amount of wheat flour substitution regarding technological, sensory and nutritive characteristics was performed. The optimal level of 20% substitution was determined using Z-score analysis, from the aspect of the best nutritive improvement and the mildest adverse impact on the technological and sensory quality. In the second research phase, comparison of the cookies with the 20% celery root powder substitution, dehydrated by different methods, indicated that combined dehydration showed upgraded results in terms of the overall quality of the final product, for 28.85 percentile points higher than cookies with lyophilized and for 65.24 percentile points higher than cookies with the addition of convectively dried celery root powder. The cookie containing celery powder previously osmodehydrated in molasses had higher contents of analyzed minerals (1.2-3.3 times), total phenols (10.8%) and antioxidant activities (14% for DPPH and 4% for ABTS) compared to the cookie with lyophilized powder.

15.
Food Chem Toxicol ; 188: 114663, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38631435

RESUMO

The effect of endothelial cells' exposure to dibutyl phthalate (DBP) on monocyte adhesion is largely unknown. We evaluated monocyte adhesion to DBP-exposed endothelial cells by combining three approaches: short-term exposure (24 h) of EA.hy926 cells to 10-6, 10-5, and 10-4 M DBP, long-term exposure (12 weeks) of EA.hy926 cells to 10-9, 10-8, and 10-7 M DBP, and exposure of rats (28 and 90 days) to 100, 500, and 5000 mg DBP/kg food. Monocyte adhesion to human EA.hy926 and rat aortic endothelial cells, expression of selected cellular adhesion molecules and chemokines, and the involvement of extracellular signal-regulated kinase 1/2 (ERK1/2) were analyzed. We observed increased monocyte adhesion to DBP-exposed EA.hy926 cells in vitro and to rat aortic endothelium ex vivo. ERK1/2 inhibitor prevented monocyte adhesion to DBP-exposed EA.hy926 cells in short-term exposure experiments. Increased ERK1/2 phosphorylation in rat aortic endothelium and transient decrease in ERK1/2 activation following long-term exposure of EA.hy926 cells to DBP were also observed. In summary, exposure of endothelial cells to DBP promotes monocyte adhesion, thus suggesting a possible role for this phthalate in the development of atherosclerosis. ERK1/2 signaling could be the mediator of monocyte adhesion to DBP-exposed endothelial cells, but only after short-term high-level exposure.


Assuntos
Adesão Celular , Dibutilftalato , Células Endoteliais , Monócitos , Dibutilftalato/toxicidade , Animais , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Adesão Celular/efeitos dos fármacos , Humanos , Ratos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Masculino , Aorta/efeitos dos fármacos , Aorta/citologia , Linhagem Celular , Fosforilação/efeitos dos fármacos
16.
Chem Biol Interact ; 399: 111120, 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-38944327

RESUMO

Dibutyl phthalate (DBP) is widely used in many consumer and personal care products. Here, we report vascular endothelial response to DBP in three different exposure scenarios: after short-term exposure (24 h) of human endothelial cells (ECs) EA.hy926 to 10-6, 10-5, and 10-4 M DBP, long-term exposure (12 weeks) of EA.hy926 cells to 10-9, 10-8, and 10-7 M DBP, and exposure of rats (28 and 90 days) to 100, 500, and 5000 mg DBP/kg food. We examined different vascular functions such as migration of ECs, adhesion of ECs to the extracellular matrix, tube formation, the morphology of rat aorta, as well as several signaling pathways involved in controlling endothelial function. Short-term in vitro exposure to DBP increased migration of ECs through G protein-coupled estrogen receptor, extracellular signal-regulated kinase 1/2, and nitric oxide (NO) signaling and decreased adhesion to gelatin. Long-term in vitro exposure to DBP transiently increased EC migration and had a bidirectional effect on EC adhesion to gelatin and tube formation. These effects were accompanied by a sustained increase in NO production and endothelial NO synthase (eNOS) and Akt activity. In vivo, exposure to DBP for 90 days decreased the aortic wall-to-lumen ratio and increased eNOS and Akt phosphorylation in ECs of rat aorta. This comparative investigation has shown that exposure to DBP may affect vascular function by altering EC migration, adhesion to gelatin, and tube formation after short- and long-term in vitro exposure and by decreasing the aortic wall-to-lumen ratio in vivo. The eNOS-NO and Akt signaling could be important in mediating the effects of DBP in long-term exposure scenarios.


Assuntos
Adesão Celular , Movimento Celular , Dibutilftalato , Células Endoteliais , Animais , Dibutilftalato/toxicidade , Humanos , Ratos , Movimento Celular/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Transdução de Sinais/efeitos dos fármacos , Óxido Nítrico/metabolismo , Aorta/efeitos dos fármacos , Linhagem Celular , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo
17.
Toxicology ; 502: 153737, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38311099

RESUMO

Aryl hydrocarbon receptor (AHR) is one of the main mediators of the toxic effects of benzo[a]pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, a vast number of BaP- and TCDD-affected genes may suggest a more complex transcriptional regulatory network driving common adverse effects of these two chemicals. Unlike TCDD, BaP is rapidly metabolized in the liver, yielding products with a questionable ability to bind and activate AHR. In this study, we used transcriptomics data from the BaP- and TCCD-exposed human liver cell line HepG2, and performed differential eigengene network analysis to understand the correlation among genes and to untangle the common regulatory mechanism in the action of BaP and TCDD. The genes were grouped into 11 meta-modules with an overall preservation of 0.72 and were also segregated into three consensus time clusters: 12, 24, and 48 h. The analysis showed that the consensus genes in each time cluster were either directly regulated by the AHR or the AHR-TF interactions. Some TFs form a direct physical interaction with AHR such as ESR1, FOXA1, and E2F1, whereas others, including CTCF, RXRA, FOXO1, CEBPA, CEBPB, and TP53 show an indirect interaction with AHR. The analysis of biological processes (BPs) identified unique and common BPs in BaP and TCDD samples, with DNA damage response detected in all three time points. In summary, we identified a consensus transcriptional regulatory network common for BaP and TCDD consisting of direct AHR targets and AHR-TF targets. This analysis sheds new light on the common mechanism of action of a genotoxic (BaP) and non-genotoxic (TCDD) chemical in liver cells.


Assuntos
Benzo(a)pireno , Dibenzodioxinas Policloradas , Humanos , Benzo(a)pireno/toxicidade , Dibenzodioxinas Policloradas/toxicidade , Consenso , Fígado/metabolismo , Linhagem Celular Tumoral , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo
18.
Foods ; 13(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38472895

RESUMO

This study focuses on predicting and optimizing the quality parameters of cookies enriched with dehydrated peach through the application of Support Vector Machine (SVM) and Artificial Neural Network (ANN) models. The purpose of the study is to employ advanced machine learning techniques to understand the intricate relationships between input parameters, such as the presence of dehydrated peach and treatment methods (lyophilization and lyophilization with osmotic pretreatment), and output variables representing various quality aspects of cookies. For each of the 32 outputs, including the parameters of the basic chemical compositions of the cookie samples, selected mineral contents, moisture contents, baking characteristics, color properties, sensorial attributes, and antioxidant properties, separate models were constructed using SVMs and ANNs. Results showcase the efficiency of ANN models in predicting a diverse set of quality parameters with r2 up to 1.000, with SVM models exhibiting slightly higher coefficients of determination for specific variables with r2 reaching 0.981. The sensitivity analysis underscores the pivotal role of dehydrated peach and the positive influence of osmotic pretreatment on specific compositional attributes. Utilizing established Artificial Neural Network models, multi-objective optimization was conducted, revealing optimal formulation and factor values in cookie quality optimization. The optimal quantity of lyophilized peach with osmotic pretreatment for the cookie formulation was identified as 15%.

19.
Foods ; 13(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38890887

RESUMO

This study investigates the applicability of the Peleg model to the osmotic dehydration of various sweet potato variety samples in sugar beet molasses, addressing a notable gap in the existing literature. The osmotic dehydration was performed using an 80% sugar beet molasses solution at temperatures of 20 °C, 35 °C, and 50 °C for periods of 1, 3, and 5 h. The sample-to-solution ratio was 1:5. The objectives encompassed evaluating the Peleg equation's suitability for modeling mass transfer during osmotic dehydration and determining equilibrium water and solid contents at various temperatures. With its modified equation, the Peleg model accurately described water loss and solid gain dynamics during osmotic treatment, as evidenced by a high coefficient of determination value (r2) ranging from 0.990 to 1.000. Analysis of Peleg constants revealed temperature and concentration dependencies, aligning with previous observations. The Guggenheim, Anderson, and de Boer (GAB) model was employed to characterize sorption isotherms, yielding coefficients comparable to prior studies. Effective moisture diffusivity and activation energy calculations further elucidated the drying kinetics, with effective moisture diffusivity values ranging from 1.85 × 10-8 to 4.83 × 10-8 m2/s and activation energy between 7.096 and 16.652 kJ/mol. These findings contribute to understanding the complex kinetics of osmotic dehydration and provide insights into the modeling and optimization of dehydration processes for sweet potato samples, with implications for food processing and preservation methodologies.

20.
Int J Dermatol ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39021235

RESUMO

The skin of newborns is classified as sensitive, with a higher risk of skin barrier disruption and irritation of a diapered area. Despite dermatologist recommendations to use only water and a cloth for cleaning, most of the population still relies on the comforts of modern parenting, which includes intensive daily usage of baby wet wipes. Novel baby formulations are designed following the concept of infant skin health, containing a gentle cleanser, suitable emollient, and buffer system enabling a slightly acidic pH value and they are free of ethyl alcohol. Thus, it is important to understand the chemical background of such a complex liquid formulation, with emphasis on its safety. In line with this, the present paper discusses the scientific background of various chemical compounds found in baby wipe formulations to improve the understanding of wet wipe designs and direct them toward more skin-friendly solutions.

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