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1.
Inflamm Res ; 73(8): 1311-1332, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38839628

RESUMO

BACKGROUND: Regulatory T cells (Tregs) play vital roles in controlling immune reactions and maintaining immune tolerance in the body. The targeted destruction of epidermal melanocytes by activated CD8+T cells is a key event in the development of vitiligo. However, Tregs may exert immunosuppressive effects on CD8+T cells, which could be beneficial in treating vitiligo. METHODS: A comprehensive search of PubMed and Web of Science was conducted to gather information on Tregs and vitiligo. RESULTS: In vitiligo, there is a decrease in Treg numbers and impaired Treg functions, along with potential damage to Treg-related signaling pathways. Increasing Treg numbers and enhancing Treg function could lead to immunosuppressive effects on CD8+T cells. Recent research progress on Tregs in vitiligo has been summarized, highlighting various Treg-related therapies being investigated for clinical use. The current status of Treg-related therapeutic strategies and potential future directions for vitiligo treatment are also discussed. CONCLUSIONS: A deeper understanding of Tregs will be crucial for advancing Treg-related drug discovery and treatment development in vitiligo.


Assuntos
Linfócitos T Reguladores , Vitiligo , Vitiligo/imunologia , Vitiligo/terapia , Humanos , Linfócitos T Reguladores/imunologia , Animais , Linfócitos T CD8-Positivos/imunologia
2.
Comput Struct Biotechnol J ; 23: 2623-2636, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39021583

RESUMO

The rapid advancement of sequencing technologies has enabled the generation of vast datasets, allowing for the in-depth analysis of sequencing data. This analysis has facilitated the validation of novel pathogenesis hypotheses for understanding and treating diseases through ex vivo and in vivo experiments. Androgenetic alopecia (AGA), a common hair loss disorder, has been a key focus of investigators attempting to uncover its underlying mechanisms. Abnormal changes in mRNA, proteins, and metabolites have been identified in individuals with AGA, and future developments in sequencing technologies may reveal new biomarkers for AGA. By integrating multiple omics analysis datasets such as genomics, transcriptomics, proteomics, and metabolomics-along with clinical phenotype data-we can achieve a comprehensive understanding of the molecular underpinnings of AGA. This review summarizes the data-mining studies conducted on various omics analysis datasets as related to AGA that have been adopted to interpret the biological data obtained from different omics layers. We herein discuss the challenges of integrative omics analyses, and suggest that collaborative multi-omics studies can enhance the understanding of the complete pathomechanism(s) of AGA by focusing on the interaction networks comprising DNA, RNA, proteins, and metabolites.

3.
Ann N Y Acad Sci ; 1537(1): 155-167, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38922711

RESUMO

This study aimed to investigate the protective effect of NAcM-OPT, a small molecule inhibitor of defective in cullin neddylation 1 (DCN1), on H2O2-induced oxidative damage in keratinocytes. Immortalized human keratinocytes (HaCaT cells) were treated with NAcM-OPT and exposed to oxidative stress. CCK-8 assays were used to measure cell viability. The mGFP-RFP-LC3 dual fluorescent autophagy indicator system was utilized to evaluate changes in autophagic flux. Western blotting was used to measure the expression of the autophagy-related proteins LC3 and Beclin 1. Keratinocytes were treated with the autophagy activator rapamycin, and HaCaT cell supernatant was added to PIG1 cells (immortalized human melanocytes), followed by evaluation of tyrosinase (TYR) expression via qRT-PCR. NAcM-OPT increased cell viability and cell proliferation. Furthermore, this molecule promoted autophagic flux through increased expression of autophagy-related proteins under H2O2-induced oxidative stress. Additionally, rapamycin increased the mRNA levels of TYR in PIG1 cells. Moreover, NAcM-OPT alleviated mitochondrial damage, restored mitochondrial function, and upregulated the expression of NFE2L2, HO1, NQO1, and GCLM. Importantly, NAcM-OPT also increased epidermal thickness, follicle length, and melanin synthesis under oxidative stress in vivo. These findings suggest that NAcM-OPT may be a promising small molecule antioxidant drug for the treatment of vitiligo.


Assuntos
Autofagia , Sobrevivência Celular , Peróxido de Hidrogênio , Queratinócitos , Estresse Oxidativo , Humanos , Autofagia/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/toxicidade , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células HaCaT
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