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1.
Exp Dermatol ; 33(3): e15048, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38439204

RESUMO

As the largest organ, the skin provides the first line of defence against environmental pollutants. Different pollutants have varied damage to the skin due to their own physical-chemical properties. A previous epidemiological study by our team revealed that eczema was positively correlated with different air pollutants. However, the mechanism of action from different pollutants on the skin is less known. In this work, the differences among the genotoxicity, intracellular reactive oxygen species, and barrier-related parameters caused by two kinds of air pollutants, that is, S1650b and carbon black (CB) were investigated by Western blot, TUNEL, comet assay and RNA-sequences. The results indicated that both S1650b and CB caused DNA damage of keratinocytes. With the content of lipophilic polycyclic aromatic hydrocarbons (PAH), S1650b leaked into the keratinocytes easily, which activated the aromatic hydrocarbon receptor (AhR) in keratinocytes, leading to worse damage to barrier-related proteins than CB. And CB-induced higher intracellular ROS than S1650b due to the smaller size which make it enter the keratinocytes easier. RNA-sequencing results revealed that S1650b and CB both caused DNA damage of keratinocytes, and the intervention of S1650b significantly upregulated AhR, cytochrome oxidase A1 and B1 (CYP1A1 and CYP1B1) genes, while the results showed oppositely after CB intervention. The mechanism of keratinocyte damage caused by different air particle pollutants in this study will help to expand our understanding on the air pollutant-associated skin disease at cell levels.


Assuntos
Poluentes Atmosféricos , Poluentes Ambientais , Fuligem , Material Particulado/toxicidade , Queratinócitos , Dano ao DNA , Estresse Oxidativo , Poluentes Atmosféricos/toxicidade , RNA
2.
Dermatol Surg ; 49(9): 825-831, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37384896

RESUMO

BACKGROUND: Limited information is available regarding survival outcomes and risk factors of dermatofibrosarcoma protuberans (DFSP). OBJECTIVE: To investigate the clinicopathologic characteristics and survival outcomes of DFSP. MATERIALS AND METHODS: The study cohort (7,567 patients) was selected from the Surveillance, Epidemiology, and End Results Program (2000-2018). Demographic and clinicopathologic variables, survival outcomes, and prognostic factors were analyzed. RESULTS: A total of 5,640 (74.53%) and 1,927 (25.47%) tumors were located in the skin and soft tissue, respectively. The median follow-up duration was 92 months. Median follow-up times were similar between patients with lymph node (107 months) and distant (102 months) metastases; the median survival time of the 89 patients (1.18%) who died of DFSP was significantly short (41 months, p < .001). Independent risk factors for cancer-specific mortality included age at diagnosis, histologic grade, and tumor size. Patients with tumors ≥10 cm in size or histologic grade III had significantly higher DFSP-specific mortality (7.07% and 10.08%, respectively, p < .001). Tumor locations and surgical procedures did not significantly influence survival. CONCLUSION: Dermatofibrosarcoma protuberans has a favorable survival prognosis, even in patients with node-positive or distant metastases. Dermatofibrosarcoma protuberans-specific mortality is significantly higher in patients with grade III or large (≥10 cm) tumors.


Assuntos
Dermatofibrossarcoma , Neoplasias Cutâneas , Humanos , Prognóstico , Estudos Retrospectivos , Dermatofibrossarcoma/cirurgia , Dermatofibrossarcoma/patologia , Neoplasias Cutâneas/cirurgia , Estudos de Coortes , Recidiva Local de Neoplasia/epidemiologia
3.
Front Nutr ; 10: 1121498, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36969816

RESUMO

Introduction: Dairy products have long been regarded as a controversial nutrient for the skin. However, a clear demonstration of donkey milk (DM) on skincare is required. Methods: In this study, spectrum and chemical component analyses were applied to DM. Then, the effects of DM on UVB-induced skin barrier damage and melanin pigmentation were first evaluated in vitro and in vivo. Cell survival, animal models, and expression of filaggrin (FLG) were determined to confirm the effect of DM on UVB-induced skin barrier damage. Melanogenesis and tyrosinase (TYR) activity were assessed after UVB irradiation to clarify the effect of DM on whitening activities. Further, a network pharmacology method was applied to study the interaction between DM ingredients and UVB-induced skin injury. Meanwhile, an analysis of the melanogenesis molecular target network was developed and validated to predict the melanogenesis regulators in DM. Results: DM was rich in cholesterols, fatty acids, vitamins and amino acids. The results of evaluation of whitening activities in vitro and in vivo indicated that DM had a potent inhibitory effect on melanin synthesis. The results of effects of DM on UVB­induced skin barrier damage indicated that DM inhibited UVB-induced injury and restored skin barrier function via up-regulation expression of FLG (filaggrin). The pharmacological network of DM showed that DM regulated steroid biosynthesis and fatty acid metabolism in keratinocytes and 64 melanin targets which the main contributing role of DM might target melanogenesis, cell adhesion molecules (CAMs), and Tumor necrosis factor (TNF) pathway. Discussion: These results highlight the potential use of DM as a promising agent for whitening and anti-photoaging applications.

4.
Int J Nanomedicine ; 16: 6183-6202, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522095

RESUMO

Extracellular vesicles (EVs), as nanoscale membranous vesicles containing DNAs, RNAs, lipids and proteins, have emerged as promising diagnostic and therapeutic agents for skin diseases. Here, we summarize the basic physiology of the skin and the biological characteristic of EVs. Further, we describe the applications of EVs in the treatment of dermatological conditions such as skin infection, inflammatory skin diseases, skin repair and rejuvenation and skin cancer. In particular, plant-derived EVs and clinical trials are discussed. In addition, challenges and perspectives related to the preclinical and clinical applications of EVs are highlighted.


Assuntos
Vesículas Extracelulares
5.
Biomed Pharmacother ; 138: 111534, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311532

RESUMO

Particulate matter (PM) is a common indirect indicator of air pollution and threatens public health upon prolonged exposure, leading to oxidative stress, increasing the risk of develop respiratory and cardiovascular, as well as several autoimmune diseases and cancer. Nowadays, as a first line defense against PM, skin health attracted much attention. Our review summarized the skin damage mechanism induced by PM, including damage skin barrier directly, reactive oxygen species (ROS) accumulation, autophagy, and two canonical signaling pathways. Furthermore, ROS and oxidative stress have been considered pathogenesis centers, with essential skin damage roles. Extracts from plants and natural compounds which present high antioxidant capacity could be used to treat or protect against air pollution-related skin damage. We conclude the extracts reported in recent studies with protective effects on PM-mediated skin damage. Besides, the mechanism of extracts' positive effects has been revealed partially.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Antioxidantes/farmacologia , Produtos Biológicos/farmacologia , Exposição Ambiental/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/efeitos adversos , Dermatopatias/prevenção & controle , Pele/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Pele/metabolismo , Pele/patologia , Dermatopatias/epidemiologia , Dermatopatias/metabolismo , Dermatopatias/fisiopatologia
6.
Oxid Med Cell Longev ; 2021: 6652086, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33986916

RESUMO

Together with nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H2S) is now recognized as a vital gaseous transmitter. The ubiquitous distributions of H2S-producing enzymes and potent chemical reactivities of H2S in biological systems make H2S unique in its ability to regulate cellular and organ functions in both health and disease. Acting as an antioxidant, H2S can combat oxidative species such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) and protect the skin from oxidative stress. The aberrant metabolism of H2S is involved in the pathogenesis of several skin diseases, such as vascular disorders, psoriasis, ulcers, pigment disorders, and melanoma. Furthermore, H2S donors and some H2S hybrids have been evaluated in many experimental models of human disease and have shown promising therapeutic results. In this review, we discuss recent advances in understanding H2S and its antioxidant effects on skin pathology, the roles of altered H2S metabolism in skin disorders, and the potential value of H2S as a therapeutic intervention in skin diseases.


Assuntos
Sulfeto de Hidrogênio/uso terapêutico , Dermatopatias/tratamento farmacológico , Humanos , Sulfeto de Hidrogênio/farmacologia
7.
Food Chem ; 349: 129164, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33550022

RESUMO

Premna microphylla turcz leaf juice with polysaccharides (PMPs) as its main component, are raw material of jelly-like Chinese traditional food "Guanyin tofu", which were also experiencedly used to relieve inflammation-related symptoms. Here three kinds of PMPs were extracted in alkaline (APMP), water (WPMP) and acidic (HPMP) conditions, being characteristic of RG I, high- and low-methoxyl HG pectin, respectively, in amorphous form with diverse surface microstructures, among which APMP predominantly composed of Glucose instead of galacturonic acid, showing wider molecular weight distribution and more branched chains. PMPs showed remarkable radical scavenging capability, and especially APMP at concentrations above 50 µg/mL effectively inhibited the reactive oxygen species and malondialdehyde production in LPS-stimulated RAW 264.7 macrophages, by enhancing enzymatic activities of endogenous superoxide dismutase, glutathione peroxidase and catalase, and accordingly alleviated inflammatory cytokines. Thus, PMPs could be promising non-toxic natural dietary supplement to improve chronic inflammation-induced diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Lamiaceae/química , Macrófagos/efeitos dos fármacos , Pectinas/farmacologia , Folhas de Planta/química , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Citocinas/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/enzimologia , Macrófagos/metabolismo , Camundongos , Pectinas/química , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo
8.
Photodermatol Photoimmunol Photomed ; 37(5): 395-403, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33565151

RESUMO

BACKGROUND: ΔNp63α and c-Myc are key transcription factors controlling proliferation and senescence in epithelial cells. We previously reported that the c-Myc modulator MM1 and its E3 ligase, HERC3, together with the transcription factor ΔNp63α, compose a feedback loop, which regulates proliferative senescence in MCF-10A mammary epithelial cells. However, it is unknown whether this loop is involved in skin ageing. On the other hand, ultraviolet B (UVB) rays are assumed to be the main culprits for photoageing of the epidermis, but the underlying mechanisms are obscure. AIMS: To investigate whether MM1/ΔNp63α axis is involved in UVB-induced photoageing of the epidermis. MATERIALS AND METHODS: HaCaT human immortalized keratinocytes overexpressed with MM1, knocked down with c-Myc or irradiated with UVB, were subjected to MTT assays to measure cell proliferation, as well as RT-qPCR or immunoblot to detect the members of MM1/ΔNp63α loop and the cellular senescence markers. Meanwhile, primary normal human keratinocytes (NHKs) or mice were irradiated with UVB, followed by immunoblot analysis, SA-ß-gal, haematoxylin-eosin or immunohistochemistry staining. RESULTS: Overexpression of MM1 down-regulated ΔNp63α and induced proliferative senescence in the HaCaT cells. In the HaCaT cells, NHKs and the mouse epidermis, UVB irradiation increased MM1 mRNA level and led to a down-regulation of ΔNp63α, HERC3 and c-Myc, concomitant with cellular senescence or photoageing. Additionally, knock-down of c-Myc induced proliferative senescence in the HaCaT cells and abrogated UVB-induced cellular senescence. CONCLUSIONS: UVB up-regulates MM1 and consequently modulates ΔNp63α and c-Myc, which may account for the proliferative senescence of keratinocytes and photoageing of the epidermis.


Assuntos
Epiderme , Envelhecimento da Pele , Animais , Linhagem Celular , Humanos , Queratinócitos , Camundongos , Transativadores , Fatores de Transcrição , Proteínas Supressoras de Tumor , Raios Ultravioleta
9.
Sci Rep ; 11(1): 2017, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479397

RESUMO

The experiment of inertial confinement fusion by the "ShengGuang (SG)-III" prototype laser facility is a transient and extreme reaction process within several nanoseconds, which could form a very complicated and intense electromagnetic field around the target chamber of the facility and may lead to harmful effect on people around. In particular, the biological effects arising from such specific environment field could hardly be ignored and have never been investigated yet, and thus, we reported on the investigation of the biological effects of radiation on HaCat cells and PC12 cells to preliminarily assess the biological safety of the target range of the "SG-III" prototype laser facility. The viability revealed that the damage of cells was dose-dependent. Then we compared the transcriptomes of exposed and unexposed PC12 cells by RNA-Seq analysis based on Illumina Novaseq 6000 platform and found that most significantly differentially expressed genes with corresponding Gene Ontology terms and pathways were strongly involved in proliferation, transformation, necrosis, inflammation response, apoptosis and DNA damage. Furthermore, we find increase in the levels of several proteins responsible for cell-cycle regulation and tumor suppression, suggesting that pathways or mechanisms regarding DNA damage repair was are quickly activated. It was found that "SG-III" prototype radiation could induce DNA damage and promote apoptotic necrosis.


Assuntos
Radiação Eletromagnética , Perfilação da Expressão Gênica , Lasers/efeitos adversos , Transcriptoma/genética , Animais , Apoptose/genética , Apoptose/efeitos da radiação , Pontos de Checagem do Ciclo Celular/genética , Pontos de Checagem do Ciclo Celular/efeitos da radiação , Dano ao DNA/genética , Dano ao DNA/efeitos da radiação , Reparo do DNA/genética , Reparo do DNA/efeitos da radiação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Células PC12 , Ratos , Transcriptoma/efeitos da radiação
10.
Biomed Pharmacother ; 134: 111161, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33360043

RESUMO

Artificial sunscreens are already gaining traction in order to protect the skin from sunburns, photoaging and photocarcinogenesis. However, the efficacy and safety of most artificial sunscreen constituents are hindered by their photostability, toxicity and damage to marine ecosystems. Natural selection and evolution have ensured that plants and animals have developed effective protective mechanisms against the deleterious side effects of oxidative stress and ultraviolet radiation (UV). Hence, natural antioxidants such as sun blockers are drawing considerable attention. The exact mechanism by which natural components act as sunscreen molecules has not been clearly established. However, conjugated π system is reported to play an important role in protecting the vital genetic material within the organism. Compared to artificial sunscreens, natural sunscreens with strong UV absorptive capacities are largely limited by low specific extinction value and by their inability to spread in large-scale sunscreen cosmetic applications. Previous studies have documented that natural components exert their photoprotective effects (such as improved skin elasticity and hydration, skin texture, and wrinkles) through their antioxidant effects, and through the regulation of UV-induced skin inflammation, barrier impairment and aging. This review focuses on natural antioxidant topical formulations with sun protection factor (SPF). Lignin, melanin, silymarin and other ingredients have been added to high sun protection nature sunscreens without any physical or chemical UV filters. This paper also provides a reference for adopting novel technical measures (extracting high content components, changing the type of solution, optimizing formulation, applying Nano technology, et al) to design and prepare nature sunscreen formulations equated with commercial sunscreen formulations. Another strategy is to add natural antioxidants from plants, animals, microorganisms and marine organisms as special enhancer or modifier ingredients to reinforce SPF values. Although the photoprotective effects of natural components have been established, their deleterious side effects have not been elucidated.


Assuntos
Antioxidantes/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Queimadura Solar/prevenção & controle , Protetores Solares/administração & dosagem , Administração Cutânea , Animais , Antioxidantes/efeitos adversos , Antioxidantes/isolamento & purificação , Humanos , Extratos Vegetais/efeitos adversos , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Pele/metabolismo , Pele/patologia , Pele/efeitos da radiação , Queimadura Solar/etiologia , Queimadura Solar/metabolismo , Queimadura Solar/patologia , Protetores Solares/efeitos adversos , Protetores Solares/isolamento & purificação , Raios Ultravioleta/efeitos adversos
11.
Biosci Trends ; 14(2): 104-114, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32321899

RESUMO

Transcultured human skin derived precursors (tSKPs) from adherent monolayer culture system have similar characteristics as traditional skin derived precursors (SKPs), making tSKPs a suitable candidate for regenerative medicine. tSKPs can differentiate into fibroblasts. However, little is known about the molecular mechanism of the transition from tSKPs to fibroblasts. Here, we compared the transcriptional profiles of human tSKPs and tSKPs-derived fibroblasts (tFBs) by RNA-Sequence aiming to determine the candidate genes and pathways involving in the differentiation process. A total of 1042 differentially expressed genes (DEGs) were identified between tSKPs and tFBs, with 490 genes up-regulated and 552 genes down-regulated. Our study showed that these DEGs were significantly enriched in tumor necrosis factor signaling pathway, focal adhesion, extracellular matrix-receptor interaction and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway. A further transcription factors (TFs) analysis of DEGs revealed the significantly down-expressed TFs (p21, Foxo1and Foxc1) in tFBs were mostly the downstream nodes of PI3K-Akt signaling pathway, which suggested PI3K-Akt signaling pathway might play an important role in tSKPs differentiation. The results of our study are useful for investigating the molecular mechanisms in tSKPs differentiation into tFBs, making it possible to take advantage of their potential application in regenerative medicine.


Assuntos
Células-Tronco Adultas/fisiologia , Diferenciação Celular/genética , Fibroblastos/fisiologia , Transcriptoma/fisiologia , Técnicas de Cultura de Células , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Derme/citologia , Derme/fisiologia , Proteína Forkhead Box O1/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA-Seq , Transdução de Sinais/genética
12.
Biomed Pharmacother ; 121: 109600, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707352

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: UVB is a high energy source that causes the major risk factor for sunburn and skin tumor. However, photochemical interactions lead to beneficial effects such as synthesis of vitamin D and corticosteroids. Therefore, a reasonable therapeutic regime is advocated to reduce UVB injuries but makes use of synthesizing sunlight metabolite. Many natural compounds improving plant cells resistant to oxidative stress by the harnessing of solar energy may be also used to protect human cells. Although many nature plants have shown photoprotective effects on skin, the mechanisms underlying of the effects are still ambiguous. AIM OF THE STUDY: This study evaluates the protective effects of cultivated Cordyceps against UVB-induced damage in human keratinocytes and identifies the photoprotective mechanisms using a transcriptomic network approach. MATERIALS AND METHODS: Cordyceps extract compositions were investigated by HPLC analysis. Cell survival, reactive oxygen species (ROS) generation, H2O2 content, aquaporin 3 (AQP3) level and DNA damage were determined upon UVB irradiation in the presence of Cordyceps extract. In addition, next-generation sequencing was used to profile transcriptomic alteration of 20 mJ/cm2 UVB and non-UV. Finally, a network pharmacology method was applied to study Cordyceps extract-related natural compounds and their UVB-induced differentially change targets using the Cytoscape 3.7.1 software. RESULTS: Adenosine and mannitol were the major contents in Cordyceps extract. Cordyceps caused a significant diminished in intracellular UVB-induced oxidative stress, including ROS production and intracellular H2O2 content. Besides, AQP3 which mediated intracellular signal transmission and transported H2O2 into cells was significantly increased in the presence of Cordyceps extract against UVB irradiation. In addition, DNA repair effect of Cordyceps extract after UV irradiation was proven to be effective by comet assay. Moreover, KEGG analysis showed steroid hormone biosynthesis, ovarian steroidogenesis, fat digestion and absorption were enriched in top 3 between 20 mJ/cm2 UVB and non-UV. Gene ontology (Go) analysis showed that steroid metabolic process, sterol metabolic process, and cholesterol metabolic process were enriched in top3 biology process. By using network analysis, 125 potential bioactive ingredients in Cordyceps and 201 targets were identified. Finally, signal pathway analyses suggested that the protective effects of Cordyceps compounds against low dose UVB­induced changes might target PPAR signaling pathway, cholesterol metabolism, and ovarian steroidogenesis. CONCLUSION: Cordyceps extract may be an ideal product for external use of skin which could not only avoid UVB-induced adverse effects, but also could application of metabolite products by UVB such us steroid hormone and vitamin D3.


Assuntos
Cordyceps , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Protetores contra Radiação/farmacologia , Raios Ultravioleta/efeitos adversos , Administração Tópica , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Ensaio Cometa/métodos , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Relação Dose-Resposta a Droga , Previsões , Humanos , Queratinócitos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Protetores contra Radiação/isolamento & purificação , Reprodutibilidade dos Testes
13.
Biomed Res Int ; 2019: 7039802, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781635

RESUMO

BACKGROUND: Nowadays, atmospheric pollutants, ultraviolet rays, and other factors cause the imbalance of cell redox, resulting in skin oxidative damage. There is an interaction between inflammatory response and oxidative stress, which often involve networks of reactions and serve to amplify each other. Quercetin and quercitrin, with strong antioxidant and anti-inflammatory properties, were widely applied in cardiovascular disease, osteoporsis, pulmonary disease, etc. However, the regulation mechanism of quercetin and quercitrin on various inflammatory skin diseases is still not clear. PURPOSE: In this study, quercetin and quercitrin were used to investigate whether they had anti-inflammatory and anti-ROS effects. Besides, theoretical calculation method was also adopted to preliminarily explore the mechanism of the anti-inflammatory and antioxidant effects of these two substances. METHODS: CCK-8 assay was employed to investigate the cytotoxicity. The concentration of NO measured by Griess Reaction System. Moreover, the inflammatory factors (TNF-α, IL-1ß, and IL-6) were reduced in LPS-stimulated RAW264.7 cells were tested by ELISA kits. The trend of ROS changes was detected by DCFH-DA method. Finally, the mechanism of the anti-inflammatory and antioxidant effects of these two substances was carried out by DMol3 package in Materials Studio. RESULTS: CCK-8 assay results guided that the safe concentration of quercetin and quercitrin was lower than 15.0 µg/mL and 22.4 µg/mL, respectively. Also, the concentration of NO could significantly be inhibited by quercetin and quercitrin. Besides, the ELISA results showed that TNF-α, IL-1ß, and IL-6 were reduced in LPS-stimulated RAW264.7 cells after interfering with quercetin and quercitrin. The trend of ROS changes was similar to that of inflammatory factors. Finally, the theoretical calculation illustrated that the oxygen atom on B rings may be the main site of electron cloud density changes, which may suggest a possible mechanism for the anti-inflammatory and ROS scavenging effects of quercetin and quercitrin. CONCLUSIONS: This experiment shows that LPS can induce the overactivating of macrophages and the activated macrophages can subsequently induce inflammatory storms and oxidative stress. Both quercetin and quercitrin can inhibit LPS-induced macrophage inflammation and oxidative stress by experiment and theoretical calculations.


Assuntos
Lipopolissacarídeos/efeitos adversos , Modelos Teóricos , Estresse Oxidativo/efeitos dos fármacos , Quercetina/análogos & derivados , Quercetina/farmacologia , Células RAW 264.7/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Quercetina/química , Células RAW 264.7/metabolismo , Dermatopatias/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo
14.
Stem Cells Int ; 2019: 9194560, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531027

RESUMO

BACKGROUND: Skin-derived precursors (SKPs) are promising candidates for regenerative medicine. Several studies have transcultured human SKPs (termed tSKPs) from fibroblasts (FBs) expanded in monolayer culture. Herein, we optimized the procedure by treating flasks with poly-2-hydroxyethyl methacrylate (poly-HEMA). METHODS: tSKPs generated from our adherent monolayer culture system were investigated for protein expression and differentiation capacity. The aggregated cells and the proliferative cells within tSKP spheres were detected by mix-culturing FBs expressing two different fluorescent proteins and BrdU- or EdU-positive cells, respectively. To distinguish tSKPs from FBs, we compared their phenotypes and transcriptomes. The tumorigenicity of tSKPs and FBs was also assessed in our study. RESULTS: tSKPs expressed Versican, Fibronectin, Vimentin, Sox2, and Nestin. Under appropriate stimuli, tSKPs could differentiate to mesenchymal or neural lineages. While these spheres were heterogeneous populations consisting of both proliferative and aggregated cells, the rate of proliferative cells correlated with a seeding density. tSKPs, isolated from FBs, were distinctive from FBs in cell cycle, marker expression, neural differentiation potential, and transcript profiles despite the two sharing partial similarity in certain properties. As for tumorigenesis, both tSKPs and FBs could be considered as nontumorigenic ex vivo and in vivo. CONCLUSION: tSKPs were heterogeneous populations presenting similar characteristics as traditional SKPs, while being different from FBs. The potential mixture of FBs in spheres did not affect the biosafety of tSKPs, as both of which had normal karyotype and nontumorigenicity. Taken together, we suggested tSKPs had potential applications in regenerative medicine.

15.
Curr Genomics ; 20(1): 49-60, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31015791

RESUMO

BACKGROUND: Skin-derived precursors (SKPs) display the characteristics of self-renewal and multilineage differentiation. OBJECTIVE: The study aimed to explore the molecular mechanisms of mouse SKPs differentiation into SKP-derived fibroblasts (SFBs). METHODS: We compared the microRNA (miRNA) profile in mouse SKPs and SFBs by RNA sequenc-ing. Real-time quantitative reverse transcription PCR (qRT-PCR) was performed to validate the miRNA expression. The integrated analysis of miRNA and mRNA expression data was performed to explore the potential crosstalk of miRNA-mRNA in SKP differentiation. RESULTS: 207 differentially expressed miRNAs and 835 miRNA target genes in the gene list of integrated mRNA expression profiling were identified. Gene Ontology (GO) enrichment analysis revealed that cell differentiation and cell proliferation process were significantly enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the target genes were significantly most enriched in the cytokine-cytokine receptor interaction, cancer pathways and axon guidance signaling pathway. The most upregulated and downregulated target genes were involved in the Wnt, Notch, cytokine-cytokine receptor interaction, TGF-ß, p53 and apoptotic signaling pathway. The miRNA-mRNA regulatory net-works and 507 miRNA-mRNA pairs were constructed. Seven miRNAs (miR-486-3p, miR-504-5p, miR-149-3p, miR-31-5p, miR-484, miR-328-5p and miR-22-5p) and their target genes Wnt4, Dlx2, Se-ma4f, Kit, Kitl, Inpp5d, Igfbp3, Prdm16, Sfn, Irf6 and Clu were identified as miRNA-mRNA crosstalk pairs. CONCLUSION: These genes and signaling pathways might control SKPs proliferation and SKPs differen-tiation into SFBs during the process of SKPs differentiation, which might promote the application of SKPs in the clinical treatment of skin-related diseases by regulating SKPs proliferation and SKPs differ-entiation.

16.
Stem Cells Int ; 2018: 8637812, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30123295

RESUMO

Skin-derived precursors (SKPs) are an adult stem cell source with self-renewal and multipotent differentiation. Although rodent SKPs have been discussed in detail in substantial studies, human SKPs (hSKPs) are rarely reported. Understanding the biological properties and possible mechanisms underlying hSKPs has important implications for regenerative medicine particularly clinical applications, as human-derived sources are more suitable for clinical transplantation. The finding that hSKPs derivatives, such as neural and mesodermal progeny, have both in vitro and in vivo function without any genetical modification makes hSKPs a trustable, secure, and accessible resource for cell-based therapy. Here, we provide an overview of hSKPs, describing their characteristics, originations and niches, and potential applications. A comparison between traditional and innovative culture methods used for hSKPs is also introduced. Furthermore, we discuss the challenges and the future perspectives towards the field of hSKPs. With this review, we hope to point out the current stage of hSKPs and highlight the problems that remain in this field.

17.
Differentiation ; 102: 30-39, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30056221

RESUMO

Both skin-derived precursors (SKPs) and dermal mesenchymal stem cells (dMSCs) are promising candidates for cellular therapy and regenerative medicine. To date the comparison of phenotypes and transcriptomes of mouse SKPs (mSKPs) and dMSCs has never been reported. Here we characterized and compared the biological properties and transcriptomes of mSKP and dMSCs from the same mouse dermis sample. Firstly, we analyzed mSKPs and dMSCs by use of immunocytochemistry, cell cycle analysis, and CD antigen expression. Then we conducted the osteogenic, adipogenic, and chondrogenic induced differentiation for both cell types. Lastly, we compared their genomic profiles by RNA-sequencing (RNA-Seq), and verified the results of RNA-Seq by quantitative real time reverse transcription PCR (qRT-PCR). The results suggested that mSKPs and dMSCs shared similarities in certain positive stem cells markers expression, but demonstrated difference in Nanog and Oct4 expression. mSKPs and dMSCs demonstrated similar cell cycle distribution and CD antigen expression. Both types of cells could be induced differentiated into osteocytes, adipocytes, and chondrocytes. However, RNA-Seq and qRT-PCR results indicated that mSKPs and dMSCs had distinct transcriptome profiles. The majority of enriched differentially expressed genes (DEGs) from mSKPs was immune-related, while the majority of enriched DEGs from dMSCs was differentiation/development/disease-related. Transcriptome profiles suggested that mSKPs and dMSCs might have potential usage in the relevant morbidity management. These results may indicate a molecular basis for novel stem cell-based therapeutic strategies.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Mesenquimais/citologia , Pele/citologia , Células-Tronco/citologia , Transcriptoma , Adipócitos/citologia , Animais , Linhagem da Célula , Células Cultivadas , Condrócitos/citologia , Condrogênese/fisiologia , Camundongos , Fenótipo
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