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1.
J Investig Med ; 70(7): 1443-1451, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35768141

RESUMO

The prolactin hormone (PRL) is often secreted by lactotrophic cells of the anterior pituitary and has been shown to play a role in various biological processes, including breast feeding and reproduction. The predominant form of this hormone is the 23 kDa form and acts through its receptor (PRLR) on the cell membrane. This receptor is a member of the superfamily of hematopoietic/cytokine receptors. PRL also has a 16 kDa subunit with anti-angiogenic, proapoptotic, and anti-inflammatory effects which is produced by the proteolytic breakdown of this hormone under oxidative stress. Although the common side effects of hyperprolactinemia are exerted on the reproductive system, new studies have shown that hyperprolactinemia has a wide variety of effects, including playing a role in the development of autoimmune diseases and increasing the risk of cardiovascular disease, peripartum cardiomyopathy, and diabetes among others. The range of PRL functions is increasing with the discovery of multiple sites of PRL secretion as well as PRLR expression in various tissues. This review summarizes current knowledge of the biology of PRL and its receptor, as well as the role of PRL in human pathophysiology.


Assuntos
Hiperprolactinemia , Anti-Inflamatórios , Humanos , Prolactina/metabolismo , Receptores de Citocinas , Receptores da Prolactina/metabolismo , Transdução de Sinais
2.
Artif Cells Nanomed Biotechnol ; 47(1): 1642-1652, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31027431

RESUMO

AIM: The aim of the present study was to produce chrysin-curcumin-loaded PCL-PEG nanofibres by an electrospinning technique and to evaluate the biological activity of the chrysin-curcumin-loaded PCL-PEG fibres for wound healing and its related genes using in vivo methods. MATERIALS AND METHODS: The electrospinning method was carried out for the preparation of the chrysin, curcumin and chrysin-curcumin-loaded PCL-PEG nanofibres with different concentrations. FTIR and SEM were performed to characterize the chemical structures and morphology of the nanofibres. In vitro drug release, as well as in vivo wound-healing studies were investigated in male rats. The expressions of genes related to the wound-healing process were also evaluated by real-time PCR. RESULTS: Our study showed that the chrysin-curcumin-loaded nanofibres have anti-inflammatory properties in several stages of the wound-healing process by affecting the IL-6, MMP-2, TIMP-1, TIMP-2 and iNOS gene expression. Our results demonstrated that the effect of the chrysin-loaded nanofibre, the curcumin-loaded nanofibre and the chrysin-curcumin-loaded nanofibre in the wound-healing process is dose dependent and in accordance with the obtained results in that it might affect the inflammation phase more than the other stages of the wound-healing process. CONCLUSION: We have introduced chrysin-curcumin-loaded PCL-PEG nanofibres as a novel compound for shortening the duration of the wound-healing process.


Assuntos
Curcumina/química , Curcumina/farmacologia , Portadores de Fármacos/química , Flavonoides/química , Flavonoides/farmacologia , Nanofibras/química , Cicatrização/efeitos dos fármacos , Animais , Liberação Controlada de Fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Interleucina-6/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Poliésteres/química , Polietilenoglicóis/química , Ratos , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo
3.
Chem Biol Drug Des ; 90(6): 1106-1114, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28388004

RESUMO

Wound healing is an inflammatory process. Chrysin, a natural flavonoid found in honey, has been recently investigated to have anti-inflammatory and antioxidant effects. In this work, the effects of chrysin-loaded nanofiber on the expressions of genes that are related to wound healing process such as P53, TIMPs, MMPs, iNOS, and IL-6 in an animal model study were evaluated. The electrospinning method was used for preparation the different concentrations of chrysin-loaded PCL-PEG nanofiber (5%, 10%, and 20% [w/w]) and characterized by FTIR and SEM. The wound healing effects of chrysin-loaded PCL-PEG nanofiber were in vivo investigated in rats, and the expressions of genes related to wound healing process were evaluated by real-time PCR. The study results showed chrysin-loaded PLC-PEG compared to chrysin ointment and control groups significantly increase IL-6, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 (p < .05). On the other hand, nanofibers containing chrysin significantly decreased p53 and iNOS expression compared to chrysin ointment and control groups (p < .05). According to the results, chrysin-loaded PCL-PEG-PCL nanofibers have positive effects on the expression of the genes that have pivotal role in wound healing.


Assuntos
Portadores de Fármacos/química , Flavonoides/farmacologia , Nanofibras/química , Cicatrização/efeitos dos fármacos , Animais , Flavonoides/química , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 8 da Matriz/genética , Metaloproteinase 8 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Microscopia Eletrônica de Varredura , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Poliésteres/química , Polietilenoglicóis/química , Ratos , Espectroscopia de Infravermelho com Transformada de Fourier , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
4.
Drug Res (Stuttg) ; 67(4): 211-216, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28166590

RESUMO

Despite the advances in medicine, cancer remains as one of the leading causes of the death worldwide. Through our previous study, the Chrysin loaded PGLA/PEG has been synthesized, and its physico-chemical properties were characterized. The aim of the present study was to evaluate the Chrysin loaded PGLA/PEG nanoparticle therapeutic effects on TIMP-1, TIMP-2, MMP-2, MMP-9 and PI3k expression in Mouse 4T1 breast tumor model.30 mice were enrolled in the current study, and the mice were randomly divided into 3 groups: untreated (n=10), Chrysin treatment (n=10) and Chrysin-loaded PLGA/PEG-based treatment (n=10). 1064T1 mammary carcinoma cells subcutaneously inoculated in the flank on mice orthotopically. After the treatments, the primary tumors were isolated from the Mice under anesthesia. For RNA extraction, the isolated tissues were frozen in -70°C. RNA extraction was performed by using RNA extraction kit. The expression of TIMP-1, TIMP-2, MMP-2 and MMP-9 were measured by the real time PCR.The study results showed the expression of TIMP-1 and TIMP-2 in Chrysin-loaded PLGA/PEG treatment groups was higher than Chrysin receiving one. Also, the results showed that the MMP-9 and MMP-2 expressions were reduced after Chrysin loaded PLGA/PEG treatment. The reduction of the mentioned genes was greater in Chrysin-loaded PLGA/PEG treatment group in comparison with Chrysin receiving group.According to our present study, expression of the mentioned genes after treatments, Chrysin; especially, Chrysin-loaded PLGA/PEG could be proposed as a new component in the cancer therapy for reducing the progression and metastasis.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Flavonoides/uso terapêutico , Ácido Láctico/química , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Ácido Poliglicólico/química , Animais , Antineoplásicos/administração & dosagem , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Portadores de Fármacos/química , Feminino , Flavonoides/administração & dosagem , Humanos , Neoplasias Mamárias Experimentais/patologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Nanopartículas/química , Fosfatidilinositol 3-Quinases/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo
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