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1.
Sci Adv ; 8(15): eabg8335, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35417243

RESUMO

Osteonecrosis of the femoral head (ONFH) commonly occurs after glucocorticoid (GC) therapy. The gut microbiota (GM) participates in regulating host health, and its composition can be altered by GC. Here, this study demonstrates that cohousing with healthy mice or colonization with GM from normal mice attenuates GC-induced ONFH. 16S rRNA gene sequencing shows that cohousing with healthy mice rescues the GC-induced reduction of gut Lactobacillus animalis. Oral supplementation of L. animalis mitigates GC-induced ONFH by increasing angiogenesis, augmenting osteogenesis, and reducing cell apoptosis. Extracellular vesicles from L. animalis (L. animalis-EVs) contain abundant functional proteins and can enter the femoral head to exert proangiogenic, pro-osteogenic, and antiapoptotic effects, while its abundance is reduced after exposure to GC. Our study suggests that the GM is involved in protecting the femoral head by transferring bacterial EVs, and that loss of L. animalis and its EVs is associated with the development of GC-induced ONFH.


Assuntos
Vesículas Extracelulares , Microbioma Gastrointestinal , Osteonecrose , Animais , Vesículas Extracelulares/metabolismo , Glucocorticoides/metabolismo , Glucocorticoides/farmacologia , Camundongos , Osteonecrose/metabolismo , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo
2.
Theranostics ; 10(8): 3779-3792, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32206122

RESUMO

Healing of the chronic diabetic ulceration and large burns remains a clinical challenge. Therapeutic fasting has been shown to improve health. Our study tested whether fasting facilitates diabetic and burn wound healing and explored the underlying mechanism. Methods: The effects of fasting on diabetic and burn wound healing were evaluated by analyzing the rates of wound closure, re-epithelialization, scar formation, collagen deposition, skin cell proliferation and neovascularization using histological analyses and immunostaining. In vitro functional assays were conducted to assess fasting and refeeding on the angiogenic activities of endothelial cells. Transcriptome sequencing was employed to identify the differentially expressed genes in endothelial cells after fasting treatment and the role of the candidate genes in the fasting-induced promotion of angiogenesis was demonstrated. Results: Two times of 24-h fasting in a week after but especially before wound injury efficiently induced faster wound closure, better epidermal and dermal regeneration, less scar formation and higher level of angiogenesis in mice with diabetic or burn wounds. In vitro, fasting alone by serum deprivation did not increase, but rather reduced the abilities of endothelial cell to proliferate, migrate and form vessel-like tubes. However, subsequent refeeding did not merely rescue, but further augmented the angiogenic activities of endothelial cells. Transcriptome sequencing revealed that fasting itself, but not the following refeeding, induced a prominent upregulation of a variety of pro-angiogenic genes, including SMOC1 (SPARC related modular calcium binding 1) and SCG2 (secretogranin II). Immunofluorescent staining confirmed the increase of SMOC1 and SCG2 expression in both diabetic and burn wounds after fasting treatment. When the expression of SMOC1 or SCG2 was down-regulated, the fasting/refeeding-induced pro-angiogenic effects were markedly attenuated. Conclusion: This study suggests that fasting combined with refeeding, but not fasting solely, enhance endothelial angiogenesis through the activation of SMOC1 and SCG2, thus facilitating neovascularization and rapid wound healing.


Assuntos
Diabetes Mellitus Experimental/dietoterapia , Jejum , Neovascularização Fisiológica , Osteonectina/metabolismo , Reepitelização , Secretogranina II/metabolismo , Animais , Queimaduras/terapia , Linhagem Celular , Proliferação de Células , Cicatriz/metabolismo , Células Endoteliais , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pele/metabolismo , Pele/patologia
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