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1.
Ann Dermatol ; 31(5): 530-537, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33911645

RESUMO

BACKGROUND: Androgenic alopecia (AGA) is the most common type of hair loss. It is likely inherited genetically and is promoted by dihydrotestosterone. 5α-reductase has been proven a good target through finasteride use. However, the pathogenesis of AGA cannot be fully explained based only on dihydrotestosterone levels. OBJECTIVE: To identify similar hairloss inhibition activity of RE-ORGA with mode of action other than finasteride. METHODS: We prepared RE-ORGA from Korean herb mixtures. We performed MTT assays for cytotoxicity, Cell Counting Kit-8 assays for cell proliferation, and western blot to identify expression levels of 5α-reductase and Bax. RNA-sequencing was performed for the expression patterns of genes in dihydrotestosterone-activated pathways. Anti-inflammatory activity was also assessed by the expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6. RESULTS: REORGA could promote the proliferation of human dermal papilla cells and showed low cytotoxicity. It also inhibited the expression of 5α-reductases and Bax in the cells. RNA-sequencing results verified that the mRNA expressions of SRD5A1, Bax, transforming growth factor-beta 1 (TGF-ß1), and TGF-ß1 induced transcript 1 (TGFß1I1) were decreased, whereas expression of protein tyrosine kinase 2 beta (PTK2ß) was more elevated. REORGA also showed anti-inflammatory activity through decreased mRNA levels of TNF-α. CONCLUSION: Transcriptionally, up-regulation of PTK2ß and concomitant down-regulation of TGFß1I1 imply that RE-ORGA can modulate androgen receptor sensitivity, decreasing the expression of 5α-reductase type II and Bax together with TGF-ß1 transcripts; RE-ORGA also showed partial anti-inflammatory activity. Overall, RE-ORGA is expected to alleviate hair loss by regulating 5α-reductase activity and the receptor's androgen sensitivity.

2.
Carbohydr Polym ; 184: 342-353, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29352928

RESUMO

The use of injectable hydrogel formulations have been suggested as a promising strategy for the treatment of degenerative disc disease to both restore the biomechanical function and reduce low back pain. In this work, a new thermo-sensitive injectable hydrogels with tunable thermo-sensitivity and enhanced stability were developed with N-hexanoylation of glycol chitosan (GC) for treatment of degenerative disc disease, and their physico-chemical and biological properties were evaluated. The sol-gel transition temperature of the hydrogels was controlled in a range of 23-56 °Ð¡, depending on the degree of hexanoylation and the polymer concentration. In vitro and in vivo tests showed no cytotoxicity and no adverse effects in a rat model. The hydrogel filling of the defective IVD site in an ex vivo porcine model maintained its stability for longer than 28 days. These results suggest that the hydrogel can be used as an alternative material for treatment of disc herniation.


Assuntos
Quitosana/química , Hidrogéis/química , Degeneração do Disco Intervertebral/tratamento farmacológico , Deslocamento do Disco Intervertebral/tratamento farmacológico , Animais , Linhagem Celular , Quitosana/uso terapêutico , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Ratos , Suínos , Temperatura
3.
Tissue Eng Part A ; 23(7-8): 323-334, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28051358

RESUMO

Although bone morphogenetic protein-2 (BMP-2) has been frequently used to stimulate bone formation, it has several side effects to be addressed, including the difficulty in optimization of clinically relevant doses and unwanted induction of cancerous signaling processes. In this study, an osteogenic peptide (OP) derived from BMP-2 was investigated as a substitute for BMP-2. In vitro studies showed that OP was able to enhance the osteogenic differentiation and mineralization of human mesenchymal stem cells (hMSCs). The peptides were then conjugated onto biocompatible poly-ι-lactide electrospun nanofibers through polydopamine chemistry. Surface chemical analysis proved that more than 80% of the peptides were stably retained on the nanofiber surface after 8 h of polydopamine coating during at least 28 days, and the amount of peptides that was retained increased depending on the polydopamine coating time. For instance, about 65% of the peptides were retained on nanofibers after 4 h of polydopamine coating. Also, a relatively small dose of peptides could effectively induce bone formation in in vivo critical-sized defects on the calvarial bones of mice. More than 50.4% ± 16.9% of newly formed bone was filled within the defect after treatment with only 10.5 ± 0.6 µg of peptides. Moreover, these groups had similar elastic moduli and contact hardnesses with host bone. Taken together, our results suggest that polydopamine-mediated OP immobilized on nanofibers can modulate the retention of relatively short lengths of peptides, which might make this an effective therapeutic remedy to guide bone regeneration using a relatively small amount of peptides.


Assuntos
Indóis/química , Células-Tronco Mesenquimais/citologia , Nanofibras/química , Peptídeos/química , Peptídeos/farmacologia , Polímeros/química , Animais , Proteína Morfogenética Óssea 2 , Regeneração Óssea/efeitos dos fármacos , Células Cultivadas , Feminino , Humanos , Camundongos , Alicerces Teciduais
4.
J Periodontol ; 84(10): 1434-44, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23305145

RESUMO

BACKGROUND: Human periodontal ligament stem cells (hPDLSCs) are promising mesenchymal stem cells that are readily accessible. However, there is as yet no consensus as to the optimal culture medium for hPDLSCs. Thus, the purpose of the present study is to determine the optimal culture medium for long-term expansion of hPDLSCs. METHODS: hPDLSCs were isolated from healthy third molars, and the most widely used medium formulations in previous studies were used: 1) an α minimum essential medium-based medium formulation (MBM); and 2) a Dulbecco's minimum essential medium-based medium formulation. Passage 5 (P5) and P8 were evaluated with the two media for cell proliferation, differentiation, and immunophenotype. RESULTS: hPDLSCs that were primarily cultured in MBM were far more proliferated than those grown in DBM. In general, application of the MBM for longer periods produced greater cell growth and osteogenic differentiation. Furthermore, MBM-precultured hPDLSCs exhibited a greater degree of cell proliferation and a greater production of mineralized tissue and alkaline phosphatase (ALP) activity in vitro, although the levels of both were dependent on the culture medium used. With respect to long-term expansion, the P5 hPDLSCs grew and produced the largest amount of mineralized nodules faster than the P8 hPDLSCs, but both passages exhibited a similar phenotype for stemness and ALP activity. CONCLUSION: The present study indicates that the inherent capacity of hPDLSCs could be maintained until a later passage, P8 in MBM, and MBM appears to be an optimal choice for manipulating the finest and most stable hPDLSCs.


Assuntos
Técnicas de Cultura de Células , Meios de Cultura/química , Células-Tronco Mesenquimais/fisiologia , Ligamento Periodontal/citologia , Adulto , Fosfatase Alcalina/análise , Antígenos CD/análise , Antígenos CD19/análise , Antígenos de Superfície/análise , Antígeno CD146/análise , Calcificação Fisiológica/fisiologia , Contagem de Células , Diferenciação Celular/fisiologia , Proliferação de Células , Forma Celular/fisiologia , Sobrevivência Celular/fisiologia , Química Farmacêutica , Endoglina , Feminino , Citometria de Fluxo , Humanos , Receptores de Hialuronatos/análise , Imunofenotipagem , Osteogênese/fisiologia , Fenótipo , Receptores de Superfície Celular/análise , Fatores de Tempo
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