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1.
Eur J Pharmacol ; 868: 172881, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31866405

RESUMO

Psoriasis is a chronic, inflammatory skin disease with high incidence and high rates of relapse, for which no satisfactory treatments are currently available. Yes-associated protein (YAP) is highly expressed in psoriasis and may regulate the proliferation and apoptosis of keratinocytes. Danshen is a traditional Chinese medicine, commonly used in the treatment of psoriasis. Danshensu is the most abundant water-soluble component of Danshen, but its therapeutic mechanism is still unclear. In this study, MTT was used to detect the effects of different danshensu concentrations (0.125, 0.25, 0.5 mmol/l) on the proliferation of an M5-based psoriasis cell model. The effects of danshensu on cell cycle and apoptosis were detected by flow cytometry. Cyclins and apoptosis-related proteins were evaluated by Western blot. Danshensu (20, 40, 80 mg/kg/day) was administered intraperitoneally to the imiquimod (IMQ) psoriasis mouse model. After 7 days, the expression of YAP in the lesions was detected by immunohistochemistry and Western blot. We found that danshensu reduced the expression of YAP in the M5 psoriasis cell model, inhibited cell proliferation, induced cell cycle arrest in G0/G1 phase, and promoted cell apoptosis. All these effects were partly reverted by YAP overexpression. The skin lesions of IMQ mice were thinned and the scales reduced after intragastric administration of danshensu, which also resulted in dose-dependent inhibition of YAP expression. We concluded that danshensu prevents abnormal epidermis proliferation in psoriasis possibly by modulating YAP expression. Our work can provide a theoretical basis for the clinical application of Danshen in the treatment of psoriasis.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31368453

RESUMO

Necrolytic migratory erythema is most commonly associated with glucagonoma syndrome. We report a rare case of glucagonoma syndrome with necrolytic migratory erythema presenting as pruritic papules and follicular pustules in a 57-year-old woman; showing eosinophilic infiltration on histology. However, the final diagnosis was confirmed by demonstrating neuroendocrine tumour on histopathological examination of the liver metastases. Nutrition therapy was administered as a palliative treatment. This case also highlights the atypical clinical features and nonspecific histology of necrolytic migratory erythema which makes the diagnosis difficult.

3.
BMC Infect Dis ; 19(1): 506, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182059

RESUMO

BACKGROUND: Scalp mycosis is often caused by dermatophytes and was so called tinea capitis. There is no published report caused by Aspergillus protuberus. We report a rare case of kerion-type scalp mycosis caused by A. protuberus. CASE PRESENTATION: A 5-year-old girl developed pyogenic mass with pain for 8 days and got a fever for 2 days prior to admission. Surgical incision and drainage of the mass, intravenous cefuroxime and metronidazole in the local hospital aggravated the skin lesions. Species identification was performed by observation of morphologic and biochemical characteristicsand sequencing of the internal transcribed spacer (ITS) and ß-tubulin (BT2). Treatment with oral and topical antifungal agents was effective with no relapse during the six months of clinical follow-up. CONCLUSIONS: Aspergillusis a opportunistic pathogenic fungus and its infection occurs mostly in patients with underlying conditions and immunocompromised statuses. So far no report of kerion-type scalp infection has been reported. The first case of kerion-type scalp mycosis caused by A. protuberus was described to highlight the importance of mycological examination that helps to recognize rare pathogenic fungi. Any boggy lesion with hair loss over the scalp and non-responsive to antibiotics should be suspected as resulting from fungal infection, and mycological examination should be performed, especially in children.


Assuntos
Aspergillus/isolamento & purificação , Micoses/diagnóstico , Couro Cabeludo/patologia , Antifúngicos/uso terapêutico , Aspergillus/classificação , Pré-Escolar , Feminino , Humanos , Hospedeiro Imunocomprometido , Micoses/tratamento farmacológico , Micoses/microbiologia , Filogenia , Couro Cabeludo/microbiologia
4.
Cancer Chemother Pharmacol ; 84(3): 453-470, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31079220

RESUMO

PURPOSE: Cancer, a major public health problem, exhibits significant redox alteration. Thioredoxin (Trx) system, including Trx and Trx reductase (TrxR), as well as Trx-interacting protein (TXNIP) play important roles in controlling the cellular redox balance in cancer cells. In most cancers, Trx and TrxR are usually overexpressed and TXNIP is underexpressed. In recent years, some agents targeting Trx, TrxR, and TXNIP were used to explore a therapy approach for cancer patients. METHODS: A systematic search of PMC and the PubMed Database was conducted to summarize the potential of Trx system inhibitors for cancer treatment. RESULTS: In this article, we first summarize the functions of Trx, TrxR, and TXNIP in cancers. We also review some small molecule inhibitors of Trx/TrxR and D-allose (TXNIP inducer) and discuss their antitumor mechanisms. We highlight the combined inhibition of Trx system and GSH system in cancer therapy. We expect that a highly specific and selective antitumor agent with no cytotoxicity on human normal cells could be developed in the future. CONCLUSION: In conclusion, Trx system may be very promising for clinical therapy of cancer in the future.

5.
J Invest Dermatol ; 139(8): 1798-1808.e5, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30738056

RESUMO

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Several previous studies have shown that fibulin-3 participates in the occurrence and development of various tumors; however, its role in cSCC remains unknown. In the present study, we observed that the expression of fibulin-3 was downregulated in cSCC tissues compared with normal skin tissues, which was due to fibulin-3 promoter methylation. In vitro, knockdown of fibulin-3 in cSCC cell lines A431 and SCL-1 cells promoted cell proliferation, protected cells against apoptosis and enhanced migration and invasion abilities. Conversely, overexpression of fibulin-3 inhibited cell proliferation by promoting growth arrest during the G1/S phase transition, induced apoptosis, and reduced migration and invasion abilities. These anticarcinogenic effects of fibulin-3 were associated with inhibition of the AKT signaling pathway. Through a mouse xenograft model, we found that fibulin-3 overexpression inhibited the cSCC tumor growth in vivo. Our results suggest that fibulin-3 has anti-tumorigenic activities in cSCC. Downregulation of fibulin-3 is involved in cSCC development and it may serve as a novel therapeutic target of this disease.

7.
J Invest Dermatol ; 139(1): 71-80, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30009832

RESUMO

Psoriasis is a chronic inflammatory skin disease characterized by abnormal proliferation of epidermal keratinocytes and infiltration of inflammatory cells. CRNN is a major component of the cornified cell envelope and implicated in several epithelial malignancies. Here, we show that CRNN expression was increased in the lesioned epidermis from the patients with psoriasis vulgaris and skin lesions from the imiquimod (IMQ)-treated mice. Expression of CRNN in cultured keratinocytes (HEKa and HaCaT) was also induced by M5, a mixture of five pro-inflammatory cytokines (i.e., IL-17A, IL-22, IL-1α, oncostatin M, and TNF-α). Lentiviral expression of CRNN increased cell proliferation by inducing cyclin D1. Conversely, knockdown of CRNN by small interfering RNA suppressed G1/S transition and attenuated the M5-induced proliferation. In addition, CRNN overexpression increased the phosphorylation and activation of phosphoinositide 3-kinase and Akt. Inactivation of the phosphoinositide 3-kinase and Akt pathways using small interfering RNA or selective inhibitors (LY294002 and MK2206) reduced the proliferative effects of CRNN. Furthermore, topical use of anti-psoriatic calcipotriol effectively decreased expression of CRNN, inhibited the Akt activation and improved the IMQ-stimulated psoriasis-like pathologies. Taken together, these results suggest that induced expression of CRNN may contribute to the pathogenesis of psoriasis.


Assuntos
Regulação da Expressão Gênica , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Psoríase/genética , RNA/genética , Pele/fisiopatologia , Animais , Western Blotting , Proliferação de Células , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Imiquimode/toxicidade , Queratinócitos/metabolismo , Queratinócitos/patologia , Proteínas de Membrana/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Neoplasias/biossíntese , Psoríase/metabolismo , Psoríase/patologia , Transdução de Sinais , Pele/metabolismo
8.
Sci Rep ; 8(1): 14513, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30323299

RESUMO

Psoriasis is a chronic inflammatory skin disease with high morbidity, poor treatment methods and high rates of relapse. Keratinocyte hyperproliferation and shortened cell cycles are important pathophysiological features of psoriasis. As a known oncogene, Yes-associated protein (YAP) plays a role in promoting cell proliferation and inhibiting cell apoptosis; however, whether YAP is involved in the pathogenesis of psoriasis remains to be determined. Amphiregulin (AREG), a transcriptional target of YAP, was found to be upregulated in psoriasis, and overexpression of AREG promoted keratinocyte proliferation. In the present study, immunohistochemistry showed that YAP expression was elevated in the skin of psoriasis patients and in the Imiquimod (IMQ) mouse model of psoriasis. Knockdown of YAP in HaCaT cells inhibited cell proliferation, caused cell cycle arrest in G0/G1 phase and promoted apoptosis. These changes in YAP-knockdown HaCaT cells were related to changes in AREG expression. We concluded that YAP may play an important role in the regulation of abnormal keratinocyte proliferation via an AREG-dependent pathway and that YAP could be a new target in the treatment of psoriasis.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Anfirregulina/genética , Proliferação de Células/genética , Fosfoproteínas/genética , Psoríase/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose/genética , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular , Criança , Feminino , Regulação da Expressão Gênica/genética , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Psoríase/patologia , Transdução de Sinais/genética , Pele/metabolismo , Pele/patologia , Fatores de Transcrição , Adulto Jovem
9.
Curr Pharm Des ; 24(25): 2986-2992, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30124144

RESUMO

BACKGROUND: Cerebral ischemia is a common cause of disability and death. Ischemic brain injury results from complex pathological processes, including oxidative stress, inflammation, and apoptosis. Thioredoxin( Trx) is an important multifunctional protein, which regulates cellular redox status. Increasing studies have demonstrated that Trx provides a neuroprotective role against cerebral ischemia-induced injury. METHODS: A systematic search of PMC and the PubMed Database was conducted to summarize the protective effects of Trx against cerebral ischemia. RESULTS: This article reviews the understanding of potential effects and mechanisms of Trx against cerebral ischemia, including the anti-oxidant, anti-apoptotic and anti-inflammatory effects, as well as the activation of prosurvival pathway. We also summarize that some natural compounds induce the expression of Trx, which is involved in their anti-ischemic effects. CONCLUSION: In conclusion, Trx has a potential neuroprotection in cerebral ischemia and may be very promising for clinical therapy of ischemic stroke in the future.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/metabolismo , Isquemia Encefálica/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Tiorredoxinas/metabolismo , Animais , Anti-Inflamatórios não Esteroides/metabolismo , Apoptose/efeitos dos fármacos , Isquemia Encefálica/metabolismo , Humanos , Fármacos Neuroprotetores/metabolismo
10.
Front Aging Neurosci ; 10: 109, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29719505

RESUMO

It has been 200 years since Parkinson disease (PD) was described by Dr. Parkinson in 1817. The disease is the second most common neurodegenerative disease characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Although the pathogenesis of PD is still unknown, the research findings from scientists are conducive to understand the pathological mechanisms. It is well accepted that both genetic and environmental factors contribute to the onset of PD. In this review, we summarize the mutations of main seven genes (α-synuclein, LRRK2, PINK1, Parkin, DJ-1, VPS35 and GBA1) linked to PD, discuss the potential mechanisms for the loss of dopaminergic neurons (dopamine metabolism, mitochondrial dysfunction, endoplasmic reticulum stress, impaired autophagy, and deregulation of immunity) in PD, and expect the development direction for treatment of PD.

11.
ASN Neuro ; 10: 1759091418777438, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29809058

RESUMO

Parkinson disease (PD) is the second most common neurodegenerative movement disorder. Pharmacological animal models are invaluable tools to study the pathological mechanisms of PD. Currently, invertebrate and vertebrate animal models have been developed by using several main neurotoxins, such as 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, paraquat, and rotenone. These models achieve to some extent to reproduce the key features of PD, including motor defects, progressive loss of dopaminergic neurons in substantia nigra pars compacta, and the formation of Lewy bodies. In this review, we will highlight the pathogenic mechanisms of those neurotoxins and summarize different neurotoxic animal models with the hope to help researchers choose among them accurately and to promote the development of modeling PD.


Assuntos
Modelos Animais de Doenças , Neurotoxinas/toxicidade , Doença de Parkinson/etiologia , Doença de Parkinson/patologia , Animais , Caenorhabditis elegans , Drosophila , Vias de Administração de Medicamentos , Camundongos , Doença de Parkinson/fisiopatologia , Ratos , Caramujos , Peixe-Zebra
12.
Medicine (Baltimore) ; 96(49): e9047, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29245305

RESUMO

RATIONALE: Amelanotic malignant melanoma (AMM) is a rare subtype of malignant melanoma (MM) that manifests atypically and is easily misdiagnosed or missed altogether. The keloid type of AMM has rarely been reported. Herein, we provide information to improve the clinical diagnosis of AMM types and raise awareness to ensure early diagnosis and timely treatment. PATIENT CONCERNS: A 20-year old woman presented with a mass on her left shoulder of 1 year's duration that had been treated surgically. The lesion recurred 1 month before the present case, along with lymph node enlargement on the left supraclavicular fossa. DIAGNOSES: Histopathology and immunohistochemistry findings suggested AMM. INTERVENTIONS: The original tumor recurred 1 month later after chemotherapy, and an extended resection and a second round of chemotherapy were performed. However, the patient exhibited suspected epileptic symptoms during chemotherapy and was required to return to the local hospital for treatment. OUTCOMES: No tumor recurrence occurred within a 6-month follow-up period. LESSONS: Early AMM diagnosis has a very significant effect on prognosis. For some persistent and growing proliferative lesions, obliterative treatments should be avoided before a definitive histopathological diagnosis has been made.


Assuntos
Queloide/diagnóstico , Melanoma Amelanótico/diagnóstico , Neoplasias Cutâneas/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Ombro , Adulto Jovem
13.
Front Pharmacol ; 8: 834, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29209211

RESUMO

Diabetes mellitus is considered as a risk factor of Alzheimer's disease (AD), the front runner of neurodegenerative disorders. Streptozotocin (STZ) is a toxin for pancreatic ß-cell, which can construct a model of insulin deficient diabetes through intraperitoneal or intravenous injection. A model generated by intracerebroventricular STZ (icv-STZ) also shows numerous aspects of sporadic AD. The protective roles of tea polyphenols epigallocatechin-3-gallate (EGCG) on both two diseases were researched by some scientists. This review highlights the link between diabetes and AD and recent studies on STZ injection-induced models, and also discusses the protection of EGCG to clarify its treatment in STZ-induced diabetes and AD.

14.
Adv Exp Med Biol ; 996: 27-40, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29124688

RESUMO

There are three major types of skin cancer: melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC and SCC are often referred to as non-melanoma skin cancer (NMSC). NMSCs are relatively non-lethal and curable by surgery, hence are not reportable in most cancer registries all over the world. Melanoma is the deadliest skin cancer. Its incidence rate (case number) is about 1/10th of that for NMSC, yet its death toll is ~8 fold higher than NMSC.Melanomas arise from melanocytes which are normally located on the basement membrane with dendrites extending into the epidermal keratinocytes. A major known function of melanocytes is to produce pigments which are enclosed by lipid membrane (termed melanosomes) and distribute them into keratinocytes, thus give different shade of skin colors. BCCs arise from basal cells, which are a layer of cells located at the deepest part of epidermis. Basal cells are recently considered to be skin stem cells as they are constantly proliferating and generating keratinocytes which are continuously pushed to the surface and eventually become a dead layer of stratum corneum. Squamous cells are the keratinocytes which resembles fish scale shape, ie, those initiated from basal cells and differentiated into squamous cells. Both basal cells and squamous cells belong to keratinocytes, therefore sometimes BCC and SCC are termed keratinocyte cancer.These three types of cancer share many characteristics, yet they are very different from etiology to progression. One shared characteristic of skin cancer is that, according to the current views, they all are caused by solar or artificial ultraviolet radiation (UVR). UVA and UVB from solar UVR are the major UV bands reaching the earth surface. Both UV types cause DNA damage and immune suppression which play crucial roles in skin carcinogenesis. UVB can be directly absorbed by DNA molecules and thus causes UV-signature DNA damages; UVA, on the other hand, may function through inducing cellular ROS which then causes oxidative DNA damages [1-4]. This chapter will discuss the molecular signaling differences of UVR in melanoma and NMSC.


Assuntos
Carcinoma Basocelular/etiologia , Carcinoma de Células Escamosas/etiologia , Melanoma/etiologia , Neoplasias Induzidas por Radiação/etiologia , Transdução de Sinais/efeitos da radiação , Neoplasias Cutâneas/etiologia , Pele/efeitos da radiação , Luz Solar/efeitos adversos , Raios Ultravioleta/efeitos adversos , Animais , Carcinoma Basocelular/genética , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Dano ao DNA , Reparo do DNA/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologia , Queratinócitos/efeitos da radiação , Melanócitos/metabolismo , Melanócitos/patologia , Melanócitos/efeitos da radiação , Melanoma/genética , Melanoma/metabolismo , Melanoma/patologia , Neoplasias Induzidas por Radiação/genética , Neoplasias Induzidas por Radiação/metabolismo , Neoplasias Induzidas por Radiação/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/efeitos da radiação , Pele/metabolismo , Pele/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
15.
Exp Ther Med ; 14(1): 499-506, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28672959

RESUMO

Antimicrobial peptide LL-37 serves a function in the host defense against microbial invasion, and also regulates cell proliferation, immune activity and angiogenesis. Previous studies have reported that LL-37 participates in the development of numerous tumour types, such as ovarian cancer, lung cancer, melanoma and breast cancer. However, the function of LL-37 in the development of skin squamous cell carcinoma (SCC) has not yet been fully elucidated. The aim of the current study was to investigate how LL-37 promotes the expression of Y-box binding protein 1 (YB-1) in SCC. Short interfering RNA (siRNA) was used to inhibit the expression of YB-1, and in vitro MTT and Transwell migration assays were used to evaluate the effect of reduced YB-1 on the viability and invasion of A431 cells. A431 cells were stimulated with LL-37, and quantitative polymerase chain reaction, immunofluorescence and western blot analyses were used to detect changes in YB-1 expression. Mitogen-activated protein kinase kinase, mitogen-activated protein kinase and nuclear factor (NF)-κB signaling pathway inhibitors were also used to evaluate the mechanism of LL-37-induced YB-1 protein expression. It was found that YB-1 expression was increased in SCC tissue compared with normal tissue. Inhibiting YB-1 expression using siRNA significantly reduced the viability and suppressed the invasion of tumour cells (P<0.05 for both). LL-37 treatment at 0.05 µg/ml for 24 or 48 h significantly promoted YB-1 protein expression (P<0.05), and this was dependent on the NF-κB signaling pathway. In conclusion, the current study demonstrated that by upregulating the expression of YB-1, LL-37 can promote the occurrence and development of SCC, and this process involves the NF-κB signaling pathway.

17.
Medicine (Baltimore) ; 96(8): e6161, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28225499

RESUMO

RATIONALE: The occurrence of primary cutaneous diffuse large B cell lymphoma-other (PCDLBCL-O) has been rarely reported in the literature. Its diagnosis is based on histopathological and immunohistochemical examinations. To improve the clinical diagnosis and treatment for PCDLBCL-O, we report a case of PCDLBCL-O successfully treated by the combination of R-CHOP (A chemotherapy protocol consists of cyclophosphamide, doxorubicin, vincristine, prednisone plus Rituximab) chemotherapy and surgery. The clinical manifestations, pathological characteristics, treatment and prognosis of the case were analyzed. PATIENT CONCERNS: The patient was a 56-year-old female, presenting with red plaques and nodules in her left breast for 6 months. DIAGNOSES: Based on the clinical manifestation, histopathological and immunohistochemical results, the patient was diagnosed with PCDLBCL-O. INTERVENTIONS: She was treated with 6 courses of R-CHOP chemotherapy combined with surgical resection. OUTCOMES: In the present case, fairly good curative effect was appeared with no recurrence within the 3 years' follow-up. LESSONS: Primary cutaneous diffuse large B cell lymphoma commonly occurs on the legs (leg type), rarely on other sites of the body. The clinical manefestations are so variant that its diagnosis depends on histopathological and immunohistochemical examinations. Like systemic diffuse large B cell lymphoma, patients should be treated with systemic chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/cirurgia , Anticorpos Monoclonais Murinos/uso terapêutico , Terapia Combinada/métodos , Ciclofosfamida/uso terapêutico , Erros de Diagnóstico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Rituximab , Vincristina/uso terapêutico
18.
Mol Med Rep ; 15(1): 240-248, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27922666

RESUMO

The cathelicidin antimicrobial peptide, LL-37, is a multifunctional peptide with a broad spectrum of antimicrobial activities, such as chemotaxis and neutralizing endotoxins. Previous studies have demonstrated that it LL­37 serves a functional role in the development of numerous types of cancer including ovarian, breast, prostate and lung cancer. However, its role in the development of malignant melanoma (MM) remains unclear. To determine the role of LL­37 and the potential interaction with Y-box binding protein 1 (YB­1) in MM, RNA interference, western blot, reverse transcription-quantitative polymerase chain reaction, MTT and Transwell assays were performed. The current study demonstrated that LL­37 induced YB­1 expression, and increased tumor cell proliferation, migration and invasion of A375 and A875 MM cell lines. In addition, inhibition of nuclear factor­κB (NF­κB) attenuated LL­37­induced YB­1 expression. These results demonstrate that, through the upregulation of YB­1 expression and the activation of the NF­κB signaling pathway, LL­37 may promote the malignant progression of MM cells in vitro.


Assuntos
Catelicidinas/metabolismo , Melanoma/genética , Melanoma/patologia , Invasividade Neoplásica/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Proteína 1 de Ligação a Y-Box/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Melanoma/metabolismo , NF-kappa B/metabolismo , Invasividade Neoplásica/patologia , Interferência de RNA , RNA Interferente Pequeno/genética , Transdução de Sinais , Pele/metabolismo , Pele/patologia , Neoplasias Cutâneas/metabolismo
19.
Oncol Lett ; 12(3): 1745-1752, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27588122

RESUMO

The antimicrobial peptide LL-37 not only contributes to the host defence against microbial invasion but also regulates immune activity, angiogenesis and cell proliferation. Studies have shown that LL-37 participates in the development of a variety of tumours, such as lung cancer, ovarian cancer, breast cancer and melanoma. However, the role of LL-37 in the development of skin squamous cell carcinoma (SCC) is not clear. The present study used immunohistochemistry to confirm that the expression of human DNA-binding protein A (dbpA) was increased in SCC tissues. After stimulating SCC A341 cells, LL-37 was shown promote the proliferation, migration and invasion of these malignant cells. LL-37 also promoted the upregulation of dbpA mRNA and protein expression. In addition, after using small interfering RNA to silence the normal dbpA expression in these malignant cells, the proliferation and invasion of the tumor cells were significantly reduced. When the NF-κB inhibitor PDTC was used to inhibit the process of LL-37-stimulated cells, it was found that the original upregulated expression of dbpA was downregulated. Overall, the present demonstrated that by upregulating the expression of dbpA, LL-37 can promote the proliferation and invasion of tumour cells, and that this process depends on the NF-κB signalling pathway.

20.
Cell Stress Chaperones ; 21(5): 935-41, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27511023

RESUMO

Stress, a state of perceived threat to homeostasis, regulates a panel of important physiological functions. The human mind and body respond to stress by activating the sympathetic nervous system and secreting the catecholamines epinephrine and norepinephrine in the "fight-or-flight" response. However, the protective mechanism of acute stress is still unknown. In the present study, an acute stress mouse model was constructed by intraperitoneal injection of epinephrine (0.2 mg kg(-1)) for 4 h. Epinephrine treatment induced heat shock 70(Hsp70) expression in the stress responsive tissues, such as the cortex, hippocampus, thymus, and kidney. Further, the expression of thioredoxin-1(Trx-1), a cytoprotective protein, was also upregulated in these stress responsive tissues. In addition, the phosphorylation of cAMP-response element binding protein (CREB), a transcription factor of Trx-1, was increased after treatment with epinephrine. The block of CREB activation by H89 inhibited the acute epinephrine stress-induced Trx-1 and Hsp70 expression. Taken together, our data suggest that acute stimuli of epinephrine induced Trx-1 expression through activating CREB and may represent a protective role against stress.


Assuntos
Epinefrina/fisiologia , Expressão Gênica , Tiorredoxinas/genética , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Epinefrina/farmacologia , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Especificidade de Órgãos , Células PC12 , Ratos , Estresse Psicológico/metabolismo , Tiorredoxinas/metabolismo , Ativação Transcricional
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