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1.
BMC Public Health ; 23(1): 1178, 2023 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-37337137

RESUMO

BACKGROUND: Knowing what to eat and realizing the significance of healthful eating habits are among the important steps to promoting eating behavior. The current study aims to assess the nutrition knowledge (NK) among a convenient sample in four different countries, determine the association between different demographic factors and NK, and investigate the need for future interventions on nutrition in the four selected countries. METHODS: A cross-sectional multi-national survey study among a convenient sample of 8,191 subjects from Egypt, Syria, Saudi Arabia, and Jordan who undertook surveys between January 2019 and January 2020. A pre-tested interview questionnaire was utilized for data collection from study participants. It included three sections: i) Sociodemographic characteristics:. ii). Section two included twenty-one questions related to NK.. iii). Section three included one question about NK sources. RESULTS: About three-quarters showed inadequate nutrition knowledge (73.1%). Youth (15-24 yrs.) were more dependent on social media, with 87% using it as a primary source of NK, while adults (≥ 25 yrs.) demonstrated that 43% of them used social media. In contrast, TV was more prominent among them, with participants' characteristics such as living with parents, body mass index, and country of residence showing no association with NK. However, female sex, education, and reading nutrition articles are significantly correlated with adequate knowledge (p < 0.001). Significant predictors of satisfactory knowledge were age, sex, education, living with parents, and reading nutrition articles. CONCLUSION: The study revealed low levels of NK indicating an urgent need to implement educational programs to promote nutrition knowledge. As NK is a modifiable determinant of diet intake and can positively impact the need for developing strategies in counselling and raising awareness among the general population to improve their health status.


Assuntos
Árabes , Estado Nutricional , Adulto , Adolescente , Humanos , Feminino , Estudos Transversais , Oriente Médio , Egito , Inquéritos e Questionários , Conhecimentos, Atitudes e Prática em Saúde
2.
Toxicol Mech Methods ; 32(3): 224-232, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34651546

RESUMO

Atopic dermatitis (AD) is characterized by progressive skin inflammation. In addition, sulforaphane is an isothiocyanate organosulfur compound from cruciferous vegetables. Sulforaphane was reported to ameliorate inflammatory responses. Therefore, this study was conducted to evaluate the protective effects of sulforaphane in AD through affecting the balance between pro-inflammatory and anti-inflammatory cytokines and to evaluate its effect on AD-induced activation of the apoptotic pathway. The method of repeated rubbing of 2,4-dinitrochlorobenzene (DNCB) on shaved dorsal skin and ears of mice was used for induction of AD. After the development of AD, part of the mice was injected with 1 mg/kg sulforaphane, subcutaneously three times weekly. Samples of skin were isolated for assessment of gene and protein expression of 8-hydroxy2'-deoxyguanosine, IgE, NFκB, TNF-α, IL-1ß, IL-4, IL-10, Nrf2, and caspase-3. In addition, skin sections from different groups were stained with anti-caspase-3 antibodies. Mice in the AD group were characterized by increased gene and protein expression of 8-hydroxy2'-deoxyguanosine, IgE, NFκB, TNF-α, IL-1ß, and caspase-3 associated with reduced expression of Nrf2, IL-4, and IL-10. Treatment of AD mice with sulforaphane significantly reduced the number of scratches, dermatitis score, and ear thickness. In addition, sulforaphane significantly attenuated the gene and protein expressions produced by AD. Therefore, sulforaphane alleviated AD induced in mice through inhibition of oxidative stress, oxidative DNA damage, inflammation, and apoptosis. HIGHLIGHTSAtopic dermatitis is a chronic relapsing inflammatory disease.Sulforaphane is an isothiocyanate organosulfur compound obtained from cruciferous vegetables.Sulforaphane alleviated AD induced in mice.Sulforaphane inhibits oxidative stress, oxidative DNA damage, inflammation, and apoptosis.


Assuntos
Dermatite Atópica , Animais , Apoptose , Citocinas/metabolismo , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Modelos Animais de Doenças , Inflamação/metabolismo , Isotiocianatos/metabolismo , Isotiocianatos/uso terapêutico , Isotiocianatos/toxicidade , Camundongos , Camundongos Endogâmicos BALB C , Pele , Sulfóxidos
3.
Pharm Dev Technol ; 25(9): 1139-1149, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32729753

RESUMO

The objective of the study was to explore the potential of a novel nicotinamide extrudate as an anti-aging platform compared to the conventional gel. Nicotinamide extrudates were prepared by hot melt extrusion and characterized pharmaceutically for their thermal behavior, mositure uptake, skin adhesion, and deposition in different skin layers. The pharmacological potential of the extrudates was explored in terms of induction of skin amino acids, cellular energy estimation, 8-hydroxy-2-deoxyguanosine content, Nitrate + nitrite content and histological chacaterization of collagen area percent. Results revealed that the extrusion technique managed to amorphize nicotinamide and enhance its skin deposition (46%) compared to the gel form which only showed about 10% deposition, owing to the mucoadhesive nature of the former. Extrudates were also found superior to the gel form as demonstrated by the increased amino acids level (glycine, proline, hydroxyproline), increased cellular energy, decreased oxidative stress and increased collagen formation. Nictotinamide extrudates were proven to be a scalable promising anti-aging platform which are worthy of entering the cosmeceutical market as products.


Assuntos
Envelhecimento/efeitos dos fármacos , Colágeno/farmacologia , Cosmecêuticos/farmacologia , Géis/farmacologia , Niacinamida/farmacologia , Envelhecimento/metabolismo , Aminoácidos/metabolismo , Animais , Colágeno/química , Cosmecêuticos/química , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Feminino , Géis/química , Masculino , Niacinamida/química , Estresse Oxidativo/efeitos dos fármacos , Polímeros/química , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/metabolismo , Solubilidade/efeitos dos fármacos
4.
Exp Dermatol ; 28(1): 28-34, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30315662

RESUMO

Although there are many treatment options for skin cancer, the chemotherapeutic agents for skin cancer are linked with many adverse effects as well as the development of multidrug resistance. Sulforaphane is an isothiocyanate, which is found in cruciferous vegetables. Consumption of sulforaphane-rich diet has been linked to inhibition of UV-exposed skin carcinogenesis. Therefore, the goal of this study was to determine the ability of sulforaphane to reduce skin cancer in mice through inhibition of sulfatase-2 enzyme. Epicutaneous application of 7,12-dimethylbenz (a) anthracene was performed on the shaved dorsal skin of mice followed by croton oil. Sulforaphane (9 µmol/mouse/day) was administered to mice orally. Skin was removed from the dorsal area for assessment of sulfatase-2, glypican-3, heparan sulphate proteoglycans (HSPGs), nuclear factor (NF)κB, nuclear factor E2-related factor 2 (Nrf2), tumor necrosis factor (TNF)-α, IL-1ß and caspase-3. In addition, skin sections were stained with haematoxylin/eosin, Mallory and cytokeratin immunostaining. We found that, sulforaphane blocked sulfatase-2 activity, leading to significant elevation in HSPGs as well as significant reduction in glypican-3. In addition, sulforaphane significantly activated Nrf2 and reduced both the gene and protein expression of NFκB, TNF-α, IL-1ß and caspase-3. In parallel, stained sections obtained from skin cancer mice treated with sulforaphane showed significant reduction in hyperkeratosis, acanthosis and epithelial dysplasia. The collective results indicate that sulforaphane suppresses skin cancer via blocking sulfatase-2 with subsequent elevation in HSPGs and reduction in glypican-3. Moreover, sulforaphane attenuated skin cancer-induced activation of inflammatory and apoptotic pathways.


Assuntos
Anticarcinógenos/uso terapêutico , Isotiocianatos/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Sulfatases/antagonistas & inibidores , Animais , Antracenos , Antioxidantes/metabolismo , Apoptose , Carcinógenos , Caspase 3/metabolismo , Modelos Animais de Doenças , Glipicanas/metabolismo , Proteoglicanas de Heparan Sulfato/metabolismo , Interleucina-1beta/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Sulfatases/metabolismo , Sulfóxidos , Fator de Necrose Tumoral alfa/metabolismo
5.
Cytokine ; 106: 45-53, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29549723

RESUMO

Animals with impaired transforming growth factor (TGF)-ß1 signaling developed spontaneous lethal autoimmune inflammationand autoimmune diseases. Moreover, evidence for modified TGF-ß signaling in atopic dermatitis (AD) exists. Therefore, the goal of this study was to determine whether SB-431542, a potent and selective inhibitor of the TGF-ß type 1 receptor (TGF-ßR1), could attenuate such a severe reaction in mice. In addition, the molecular underpinnings the possible protective effects were also investigated. Repeated epicutaneous application of DNCB was performed on the ear and shaved dorsal skin of miceto induce AD-like symptoms and skin lesions. SB-431542 (1 mg/kg) was given by intra-peritoneal injection three times weekly for 3 weeks to assess the anti-pruritic effects. Serum levels of TGF-ß1, TGF-ßR1, latency-associated peptide (LAP), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 were assessed by ELISA. Moreover, the gene expression of TNF-α, IL-1ß and IL-6 were determined. Apoptotic pathway was evaluated by measuring the activity of caspase-3 and by staining skin sections with anti-caspase-3 antibodies. We found that SB-431542 alleviated DNCB-induced AD-like symptoms as quantified by skin lesion,dermatitisscore, ear thickness and scratching behavior. In parallel, SB-431542 blocked DNCB-induced elevation in serum levels of TNF-α, TGF-ß1, TGF-ßR1, LAP, IL-1ß, IL-6 and IgE. The collective results indicate that SB-431542 partially suppresses DNCB-induced AD in micevia reduction of TGF-ß1 signaling pathway associated with inhibition of inflammation and apoptosis.


Assuntos
Dermatite Atópica/induzido quimicamente , Dermatite Atópica/patologia , Receptor do Fator de Crescimento Transformador beta Tipo I/antagonistas & inibidores , Pele/patologia , Animais , Antioxidantes/metabolismo , Benzamidas/farmacologia , Biomarcadores/sangue , Caspase 3/metabolismo , Dermatite Atópica/sangue , Dermatite Atópica/genética , Dinitroclorobenzeno , Dioxóis/farmacologia , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Fibrose , Regulação da Expressão Gênica/efeitos dos fármacos , Hipersensibilidade/patologia , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Camundongos Endogâmicos BALB C , Receptor do Fator de Crescimento Transformador beta Tipo I/sangue , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Pele/efeitos dos fármacos , Fator de Crescimento Transformador beta/sangue
6.
Pharm Dev Technol ; 22(4): 545-550, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26895257

RESUMO

Indocyanine green (ICG) is a near-IR fluorescent dye with a great potential for application as photosensitizer in topical photodynamic therapy (PDT) of skin diseases. Despite its merits, its use has been hampered by its high degradation rate. Therefore, in the current article, ICG was encapsulated in a vesicular colloidal nanocarrier (transfersomes), with the aim of enhancing its therapeutic efficacy. Transfersomes were characterized for their entrapment efficiency, particle size, zeta potential, morphology, in vitro release and histopathological effect on mice skin. A pilot clinical study was conducted to test its therapeutic potential for PDT of basal cell carcinoma (BCC). Transfersomal ICG displayed particle size (∼125 nm) and a negative zeta potential (∼-31 mV). Transfersomes were also able to sustain the release of ICG >2 h. Upon incorporation of transfersomal ICG in gel form, it was found to maintain the normal histology of mice skin post-irradiation with diode laser 820 nm. Moreover, ICG transfersomal PDT achieved 80% clearance rate for BCC patients with minimal pain reported during treatment. The previous findings suggest that transfersomal nanoencapsulated ICG is a promising treatment modality for BCC.


Assuntos
Carcinoma Basocelular/tratamento farmacológico , Coloides/química , Corantes/uso terapêutico , Preparações de Ação Retardada/química , Verde de Indocianina/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Pele/efeitos dos fármacos , Administração Tópica , Animais , Carcinoma Basocelular/patologia , Corantes/administração & dosagem , Humanos , Verde de Indocianina/administração & dosagem , Masculino , Camundongos , Pessoa de Meia-Idade , Fotoquimioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Projetos Piloto , Pele/patologia , Neoplasias Cutâneas/patologia
7.
Cytokine ; 83: 64-74, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27038016

RESUMO

Scientific evidence illustrated the health hazards of exposure to nitrites for prolonged time. Nitrites affected several body organs due to oxidative, inflammatory and apoptosis properties. Furthermore, thymoquinone (TQ) had curative effects against many diseases. We tried to discover the impact of both sodium nitrite and TQ on inflammatory cytokines contents in testicular tissues and hormonal balance both in vivo and in vitro. Fifty adult male SD rats received 80mg/kg sodium nitrite and treated with either 25 or 50mg/kg TQ daily by oral-gavage for twelve weeks. Testis were removed for sperms' count. Testicular tissue homogenates were used for assessment of protein and gene expression of IL-1ß, IL-6, TNF-α, Nrf2 and caspase-3. Serum samples were used for measurement of testosterone, LH, FSH and prolactin. Moreover, all the parameters were measured in human normal testis cell-lines, CRL-7002. Sodium nitrite produced significant decrease in serum testosterone associated with raised FSH, LH and prolactin. Moreover, sodium nitrite significantly elevated TNF-α, IL-1ß, IL-6, caspase-3 and reduced Nrf2. TQ significantly reversed all these effects both in vivo and in vitro. In conclusion, TQ ameliorated testicular tissue inflammation and restored the normal balance of sex hormones induced by sodium nitrite both in vivo and in vitro.


Assuntos
Citocinas/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Nitrito de Sódio/efeitos adversos , Testículo/metabolismo , Animais , Caspase 3/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Ratos Sprague-Dawley , Nitrito de Sódio/farmacologia , Testículo/patologia
8.
Cureus ; 16(1): e51563, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38313941

RESUMO

Acne vulgaris is a common skin condition that affects millions of people worldwide. While the exact cause of acne is not fully understood, it is believed to be influenced by various factors such as the skin microbiome, host immunity, hormones, genetics, and possibly diet. There are several treatment options for acne, including antibiotics and vitamin A derivatives (retinoids). However, these treatments can have side effects, such as dryness, redness, and peeling of the skin. The relationship between diet and acne remains somewhat controversial. Studies have found that Western societies have a higher incidence of acne than non-Western societies, which is believed to be due to dietary differences. Several experiments were conducted to target the skin microbiome and treat acne with the hope of using probiotics orally or topically to regulate the immune response and reduce inflammation in acne. In addition, studies have shown that a plant-based diet can benefit individuals with acne. Avoiding dairy consumption is one of the most effective dietary changes for reducing acne. As part of our investigation, we conducted a review to determine the effect of probiotics and vegetarian diets on acne.

9.
Cureus ; 15(5): e38596, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37284388

RESUMO

Background The Wnt pathway is a major pathway in the pathogenesis of skin cancer. Moreover, crocin is one of the carotenoid compounds present in the flowers of gardenia and crocus. Crocin is responsible for the characteristic color of saffron. Aims This study was conducted to discover the therapeutic effects of crocin against skin cancer induced in mice by blocking the Wnt pathway with subsequent effects on inflammation and fibrosis. Methods For the induction of skin cancer in mice, the application of DMBA and Croton oil was used. The dorsal skin was used for the evaluation of the gene and protein expression of TGF-ß, SMAD, Wnt, ß-catenin, TNF-α, and NFκB. Part of the skin is stained with Mallory trichrome. Results The use of crocin for treating skin cancer mice significantly reduced both the number of tumors and the number of scratches. In addition, crocin inhibited epidermal hyperplasia. Finally, crocin reduced the gene expression and protein levels of Wnt, ß-catenin, SMAD, NFκB; TGF-ß and TNF-α. Conclusions Crocin produced therapeutic effects against skin cancer induced in mice by blocking the expression of Wnt followed by blocking the pro-inflammatory pathway through downregulation of NFκB and TNF-α. In addition, crocin blocked the fibrosis pathway via the downregulation of TGF-ß.

10.
Cureus ; 15(12): e50249, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38196435

RESUMO

Psoriasis is a chronic, autoinflammatory skin disease that affects approximately 100 million people worldwide. It is a systemic disease characterized by scaly, red patches on the skin and can also affect the joints. Psoriasis can significantly affect a person's physical and mental health. The prevalence rate of psoriasis may vary depending on the specific population studied and the diagnostic criteria used. Phototherapy is a safe and effective treatment for psoriasis that involves exposing the affected skin to specific wavelengths of light. It can be used alone or with other treatments for severe psoriasis. However, clinicians must choose the right light source for each type of psoriasis and monitor the patient closely during treatment to avoid adverse events. The 308 nm excimer laser is a widely used device in dermatology for treating several skin conditions, including psoriasis. Although the excimer laser can treat various dermatologic diseases, this study will focus only on its effectiveness in treating psoriasis. This study will review the use of an excimer laser, its protocol, and its side effects.

11.
J Dermatolog Treat ; 32(7): 803-811, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31868059

RESUMO

BACKGROUND AND OBJECTIVES: The incidence of skin cancer has raised in the last few years. One of the important growth factors found in the skin layers is insulin-like growth factor (IGF)-1. It is directly linked with many cancers in different organs. Therefore, we aimed to explore the therapeutic effects of blocking IGF-1 receptor (IGF-R1) pathway by PQ401 in skin cancer as well as studying its effect on tumor invasion markers. MATERIALS AND METHODS: We experimentally induced skin cancer in mice by the application of 7,12-dimethylbenz (a) anthracene. Skin samples were removed for determination of gen and protein expression of IGF-1, IGF-R1, glypican-3, MMP9, syndecan-1 and fascin-1 by Western blot and PCR. Moreover, skin sections were stained with hematoxylin/eosin and Mallory. RESULTS: Treatment with PQ401 blocked the expression of IGF-R1 in the skin, which is associated with reduction in the skin cancer-induced tumors and scratches. In addition, PQ401 ameliorated skin cancer induced formation of epidermal atypia and hyperplasia. PQ401 reduced both gene and protein expression of the tumor invasion markers, MMP9, syndecan-1 and fascin-1, without affecting gene and protein expression of glypican-3 and IGF-1 in skin cancer group. CONCLUSION: Blocking IGF-R1 has therapeutic effects against experimental skin cancer induced in mice. In addition, blocking IGF = R1 attenuated skin cancer-induced activation of tumor invasion markers.Key pointsIGF-1/IGF-R1is highly expressed in different cancers as skin cancer.Blocking IGF-R1 production ameliorated skin cancer.Blocking IGF-R1 attenuated skin cancer-induced activation of tumor invasion markers.


Assuntos
Receptor IGF Tipo 1/antagonistas & inibidores , Neoplasias Cutâneas , Animais , Epiderme , Camundongos , Pele , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/tratamento farmacológico
12.
Arch Dermatol Res ; 313(4): 263-273, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32638071

RESUMO

Glypican-3 (GPC3) is considered as a cell surface heparan sulfate proteoglycan. It is overexpressed in skin cancer and promotes tumor progression and pathogenicity. Therefore, we aimed to find out the therapeutic effects of immuno-suppressing GPC3 in skin cancer experimentally induced in mice as well as to underline molecular mechanisms especially inflammatory and apoptotic pathways. Skin cancer was experimentally induced in mice by repeated rubbing of mice skin with 7,12-dimethylbenz (a) anthracene. Mice were injected with anti-GPC3. Skin samples were isolated to investigate the gene and protein expression of GPC3, Wnt-1, NFκB, TNF-α, IGF-1, p38 MAPK and caspase-3 using PCR, Western blot and ELISA. Moreover, skin sections were stained with hematoxylin and eosin. Treating skin cancer mice with anti-GPC3 significantly blocked GPC3, which is accompanied by amelioration of skin cancer-induced increase in the numbers of tumors and scratching behavior. Moreover, anti-GPC3 attenuated skin cancer-induced increase in the expression of Wnt-1, NFκB, TNF-α, IGF-1, p38 MAPK and caspase-3. In parallel, anti-GPC3 reduced degeneration of melanocyte cells and reduced phagocytic cells epidermal hyperplasia and dysplasia in skin sections stained with hematoxylin and eosin stain. In conclusion, anti-GPC3 produced anti-tumor effects against skin cancer, which can be explained by reduction in both inflammatory and apoptotic pathways. Targeting GPC3 is a promising therapeutic approach for skin cancer.


Assuntos
Antineoplásicos/farmacologia , Carcinogênese/efeitos dos fármacos , Glipicanas/antagonistas & inibidores , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , 9,10-Dimetil-1,2-benzantraceno/administração & dosagem , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Antineoplásicos/uso terapêutico , Carcinogênese/induzido quimicamente , Carcinógenos/administração & dosagem , Carcinógenos/toxicidade , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Neoplasias Experimentais/etiologia , Pele/efeitos dos fármacos , Pele/patologia , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/patologia
13.
Dermatol Reports ; 12(2): 8651, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-33408832

RESUMO

Herbal products and home remedies, especially those used as cosmetics, are widely used worldwide. Therefore, we conducted this study to discover the pattern of use of remedies in treating hair and scalp disorders in Tabuk, North West area of Saudi Arabia. A survey about use of herbal products and home remedies was prepared to evaluate their in hair and scalp. The questionnaire was distributed to 149 female hairdressers, hair products sellers and traditional healers as well as female customers in these places. We found about forty-one plants and eleven home remedies used for hair and scalp in Tabuk area. The most widely used plants were Henna (15.01%), coconut (10.22%) and olive (8.14%). They were widely used in hair damage (32.01%), hair endings (21.95%) and hair loss (21.94%). In parallel, the most widely used home remedies were yogurt (32.42%), eggs (26.91%) and honey (23.85%). They were widely used in hair damage (45.57%), hair endings (26.91%) and hair loss (19.88%). There were no differences between participants in the pattern of use of remedies regarding their education level of age group. In conclusion, many natural herbal medicine and home remedies are still in use in North West region of Saudi Arabia for hair and scalp. There is a great shortage in medical sources of information. Finally, many of used remedies lacks important scientific information about their usage and safety.

14.
Arch Dermatol Res ; 311(8): 595-605, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31165240

RESUMO

Wnt pathway plays an important role in controlling metabolism in cancer cells. It acts as positive modulator for both cell inflammation, through activation of NFκB, and fibrosis, through activation of TGF-ß. Therefore, the aim of this study is to investigate the therapeutic effects of blocking Wnt pathway by IWP12 on skin cancer by studying its effects on skin cancer-induced inflammation and fibrosis in a mice model of skin cancer. Skin cancer was induced by application of 7,12-dimethylbenz[a]anthracene (DMBA) and croton oil on the dorsal skin of mice. Dorsal skin was removed for estimation of gene and protein expression of Wnt, ß-catenin, SMAD, TGF-ß, NFκB, TNF-α, IL-4 and IL-10. Part of the skin is stained with hematoxylin/eosin for assessment of cell structure. Treatment of mice with IWP12 completely blocked Wnt in skin cancer mice without affecting the control mice. Skin of tumorigenic mice showed marked skin hyperkeratosis, parakeratosis, acanthosis and dysplasia. Treatment with IWP12 markedly attenuated epidermal atypia and hyperplasia. In addition, IWP12 reduced expression of ß-catenin, SMAD, TGF-ß, NFκB and TNF-α associated with increase in the expression of IL-4 and IL-10. In conclusion, blocking Wnt production ameliorated skin cancer via blocking pro-inflammatory cytokines and enhancing the anti-inflammatory cytokines. Moreover, blocking Wnt attenuated skin cancer-induced activation of fibrosis pathway.


Assuntos
Antineoplásicos/farmacologia , Carcinogênese/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Proteínas Wnt/antagonistas & inibidores , Via de Sinalização Wnt/efeitos dos fármacos , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Antineoplásicos/uso terapêutico , Carcinogênese/induzido quimicamente , Óleo de Cróton/toxicidade , Citocinas/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Epiderme/efeitos dos fármacos , Epiderme/patologia , Fibrose , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , NF-kappa B/metabolismo , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/patologia , Proteínas Wnt/metabolismo
15.
Biomed Pharmacother ; 103: 362-372, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29669302

RESUMO

Hepatocellular carcinoma (HCC) is characterized by elevation in the activity of sulfatase-2, an extracellular enzyme that catalyzes removal of 6-O-sulfate groups from heparan sulfate. Therefore, we conducted this study to investigate the cytotoxic activity of the strong water-soluble antioxidant, sodium ascorbate, against HCC both in vivo and in vitro. Sodium ascorbate enhanced animal survival in vivo and reduced HepG2 cells survival. The protein levels of heparan sulfate proteoglycans (HSPGs), insulin like growth factor (IGF)-2, sulfatase-2 and glypican-3 were assessed. Inflammation was evaluated by measuring the gene and protein expression of NFκB, TNF-α, IL-1ß, IL-4, IL-6 and IL-10. We found that sodium ascorbate blocked HCC-induced activation of sulfatase-2 leading to restoration of HSPGs receptors associated with reduction in IGF-2 and glypican-3. Sodium ascorbate exerts anti-inflammatory activity by reducing the expression of NFκB, CRP, TNF-α, IL-1ß and IL-6 associated with enhanced expression of the anti-inflammatory cytokines, IL-4 and IL-10. In conclusion, cytotoxic effects of sodium ascorbate against HCC can be partially explained by inhibition of sulfatase-2, restoration of HSPGs receptors and deactivation of the inflammatory pathway.


Assuntos
Ácido Ascórbico/farmacologia , Carcinoma Hepatocelular/enzimologia , Citotoxinas/farmacologia , Neoplasias Hepáticas Experimentais/enzimologia , Sulfotransferases/antagonistas & inibidores , Sulfotransferases/biossíntese , Animais , Ácido Ascórbico/uso terapêutico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/prevenção & controle , Citotoxinas/uso terapêutico , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Neoplasias Hepáticas Experimentais/patologia , Neoplasias Hepáticas Experimentais/prevenção & controle , Masculino , Ratos , Ratos Sprague-Dawley , Sulfatases
16.
Curr Drug Deliv ; 14(3): 426-432, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27174314

RESUMO

BACKGROUND: Nanotechnology has provided substantial benefits in drug delivery, especially in the treatment of dermatological diseases. Psoriasis is a chronic inflammatory skin disease in which topical delivery of antipsoriatic agents is considered the first line treatment. OBJECTIVE: To investigate whether the encapsulation of the synthetic retinoid tazarotene in a nanocarrier based on jojoba oil would decrease its irritation potential and clinically improve its therapeutic outcome in psoriatic patients. METHOD: A microemulsion system based on jojoba wax and labrasol/plurol isostearique was prepared and characterized. RESULTS: The selected formula displayed spherical morphology, particle size of 15.49±2.41 nm, polydispersity index of 0.20 ±0.08, negative charge and low viscosity. The microemulsion provided two folds increase in skin deposition of tazarotene, correlating with higher reduction in psoriatic patients PASI scores after treatment (68% reduction in PASI scores versus 8.96% reduction with the marketed gel). No irritation was encountered in patients using microemulsion, with redness and inflammation reported with the marketed gel-treated patients. CONCLUSION: Jojoba oil microemulsion proved to be advantageous in reducing the irritancy of tazarotene, enhancing its skin deposition and achieving better therapeutic outcome in psoriatic patients.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Portadores de Fármacos/química , Psoríase/tratamento farmacológico , Retinoides/administração & dosagem , Ceras/química , Adulto , Idoso , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Nanopartículas , Resultado do Tratamento , Adulto Jovem
17.
Redox Rep ; 21(2): 50-60, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26221999

RESUMO

OBJECTIVES: Sodium nitrite, a food preservative, has been reported to increase oxidative stress indicators such as lipid peroxidation, which can affect different organs including the kidney. Here, we investigated the toxic effects of oral sodium nitrite on kidney function in rats and evaluated potential protective effects of Nigella sativa oil (NSO). METHODS: Seventy adult male Sprague-Dawley rats received 80 mg/kg sodium nitrite orally in the presence or absence of NSO (2.5, 5, and 10 ml/kg) for 12 weeks. Morphological changes were assessed by hematoxylin and eosin, Mallory trichome, and periodic acid-Schiff staining. Renal tissues were used for measurements of oxidative stress markers, C-reactive protein, cytochrome C oxidase, transforming growth factor (TGF)-beta1, monocyte chemotactic protein (MCP)-1, pJNK/JNK, and caspase-3. RESULTS: NSO significantly reduced sodium nitrite-induced elevation in serum urea and creatinine, as well as increasing normal appearance of renal tissue. NSO also prevented reductions in glycogen levels caused by sodium nitrite alone. Moreover, NSO treatment resulted in dose-dependent significant reductions in fibrosis markers after sodium nitrite-induced 3- and 2.7-fold increase in MCP-1 and TGF-beta1, respectively. Finally, NSO partially reduced the elevated caspase-3 and pJNK/JNK. DISCUSSION: NSO ameliorates sodium nitrite-induced nephrotoxicity through blocking oxidative stress, attenuation of fibrosis/inflammation, restoration of glycogen level, amelioration of cytochrome C oxidase, and inhibition of apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Nigella sativa/química , Óleos de Plantas/uso terapêutico , Nitrito de Sódio/toxicidade , Animais , Antioxidantes/metabolismo , Proteína C-Reativa/metabolismo , Caspase 3/metabolismo , Quimiocina CCL2/metabolismo , Creatinina/sangue , Fibrose/tratamento farmacológico , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/metabolismo , Ureia/sangue
18.
Eur Cytokine Netw ; 26(2): 38-45, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26553587

RESUMO

PURPOSE: Atopic dermatitis (AD) is a chronically relapsing, pruritic, eczematous skin disorder accompanying allergic inflammation. AD is triggered by oxidative stress and immune imbalance. The effect of oral arjunolic acid (AA) on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in mice was investigated. METHODS: Repeated epicutaneous application of DNCB to the ear and shaved dorsal skin of mice was performed to induce AD-like symptoms and skin lesions: 250mg/kg AA was given orally for three weeks to assess its anti-pruritic effects. Serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-10, immunoglobulin (Ig)E and caspase-3 were assessed by ELISA. RESULTS: We found that AA alleviated DNCB-induced AD-like symptoms as quantified by skin lesions, dermatitis score, ear thickness and scratching behavior. Levels of reactive oxygen species in the AA group were significantly inhibited compared with those in the DNCB group. In parallel, AA blocked a DNCB-induced reduction in serum levels of IL-4 and IL-10 associated with an attenuation of DNCB-induced increases in serum TNF-α, IL-6, IgE and caspase-3. CONCLUSIONS: The results indicate that AA suppresses DNCB-induced AD in mice via redox balance and immune modulation, and could be a safe clinical treatment for AD.


Assuntos
Citocinas/metabolismo , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Substâncias Protetoras/farmacologia , Triterpenos/farmacologia , Animais , Caspase 3/metabolismo , Citocinas/sangue , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/etiologia , Dinitroclorobenzeno/efeitos adversos , Modelos Animais de Doenças , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Contagem de Leucócitos , Camundongos , Estresse Oxidativo , Pele/imunologia , Pele/metabolismo , Pele/patologia
19.
Inflamm Allergy Drug Targets ; 13(6): 406-10, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26021324

RESUMO

Atopic dermatitis (AD) is a skin disease that is characterized by inflammation. Skin barrier dysfunction is commonly seen in AD leading to commonly seen infectious lesions in the skin of AD. Most people develop the skin inflammation condition first, before any skin lesions become visible. Suramin is potent competitive inhibitor of reverse transcriptase and blocks the infectivity and cytopathic effects. Therefore, the following study was performed to illustrate if suramin could produce protection against AD in-vivo. AD like symptoms were introduced in mice by epicutaneous application of DNCB on shaved dorsal skin and ears. 20 mg/kg suramin was taken by intra-peritoneal injection twice weekly for 3 weeks to assess their anti-pruritic effects. Serum levels of inflammatory cytokine, interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-αwere assessed by using ELISA kits. We found that suramin alleviated DNCB-induced AD-like symptoms as quantified by skin lesion, dermatitis score, ear thickness and scratching behavior. Levels of reactive oxygen species in the suramin group were significantly inhibited as compared with that in the DNCB group. In parallel, suramin blocked DNCB-induced elevation in serum TNF-α, IL-1ß, IL-6 and IgE. The collective results indicate that suramin suppresses DNCB-induced AD in mice via reduction of inflammatory mediators.


Assuntos
Anti-Inflamatórios/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Pele/patologia , Suramina/uso terapêutico , Animais , Comportamento Animal/efeitos dos fármacos , Citocinas/sangue , Dinitroclorobenzeno , Orelha Externa/patologia , Mediadores da Inflamação/metabolismo , Irritantes , Camundongos , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo
20.
Curr Pharm Biotechnol ; 16(4): 371-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25658381

RESUMO

Transcutaneous vaccination has become a widely used technique for providing immunity against several types of pathogens, taking advantage of the immune components found in the skin. The success in the field of vaccination has not only relied on the type of antigen and adjuvant delivered, but also on how they are delivered. In this regard, particulate carriers, especially nanoparticles have evoked considerable interest, owing to the desirable properties that they impart to the substance being delivered. The presentation of antigens by the nanoparticles mimics the presentation of the immunogen by the pathogen; hence, it creates a similar immune response. Furthermore, nanoparticles protect the antigen from degradation and allow its prolonged release, which maximizes its exposure to the immune cells. The most commonly used materials for the formulation of nanoparticles are either polymer-based or lipid based. This review will focus on the lipid based nanocarriers, either vesicular such as liposomes, transfersomes, and ethosomes, or non-vesicular such as cubosomes, solid lipid nanoparticles, nano-structured lipid carriers, solid in oil nanodispersions, lipoplexes, and hybrid polymeric-lipidic systems. The applications of these carriers in the field of transcutaneous immunization will be discussed in this review as well.


Assuntos
Antígenos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Imunização/métodos , Nanopartículas/administração & dosagem , Administração Cutânea , Animais , Antígenos/química , Portadores de Fármacos/química , Lipídeos/química , Nanopartículas/química , Pele/imunologia
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