251 research outputs found
Carnosol Modulates Th17 Cell Differentiation and Microglial Switch in Experimental Autoimmune Encephalomyelitis
Medicinal plants as a rich pool for developing novel small molecule therapeutic medicine have been used for thousands of years. Carnosol as a bioactive diterpene compound originated from Rosmarinus officinalis (Rosemary) and Salvia officinalis, herbs extensively applied in traditional medicine for the treatment of multiple autoimmune diseases (1). In this study, we investigated the therapeutic effects and molecule mechanism of carnosol in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Carnosol treatment significantly alleviated clinical development in the myelin oligodendrocyte glycoprotein (MOG35–55) peptide-induced EAE model, markedly decreased inflammatory cell infiltration into the central nervous system and reduced demyelination. Further, carnosol inhibited Th17 cell differentiation and signal transducer and activator of transcription 3 phosphorylation, and blocked transcription factor NF-κB nuclear translocation. In the passive-EAE model, carnosol treatment also significantly prevented Th17 cell pathogenicity. Moreover, carnosol exerted its therapeutic effects in the chronic stage of EAE, and, remarkably, switched the phenotypes of infiltrated macrophage/microglia. Taken together, our results show that carnosol has enormous potential for development as a therapeutic agent for autoimmune diseases such as MS
Induction of lncRNA MALAT1 by hypoxia promotes bone formation by regulating the miR-22-3p/CEBPD axis
Adaptation to hypoxia promotes fracture
healing. However, the underlying molecular mechanism
remains unknown. Increasing evidence has indicated that
long non-coding RNAs (lncRNAs) play crucial roles in
several diseases, including fracture healing. In the
present study, lncRNA microarray analysis was
performed to assess the expression levels of different
lncRNAs in MC3T3-E1 cells cultured under hypoxic
conditions. A total of 42 lncRNAs exhibited significant
differences in their expression, including metastasis
associated lung adenocarcinoma transcript 1 (MALAT1),
maternally expressed 3, AK046686, AK033442, small
nucleolar RNA host gene 2 and distal-less homeobox 1
splice variant 2. Furthermore, overexpression of
MALAT1 promoted osteoblast differentiation, alkaline
phosphatase (ALP) activity and matrix mineralization of
MC3T3-E1 cells, whereas its knockdown diminished
hypoxia-induced cell differentiation, ALP activity and
matrix mineralization in these cells. Moreover,
functional analysis indicated that MALAT1 regulated the
mRNA and protein expression levels of CCAAT/
enhancer binding protein δ by competitively binding to
microRNA-22-3p. Adenoviral-mediated MALAT1
knockdown inhibited fracture healing in a mouse model.
Taken together, the results indicated that MALAT1 may
serve a role in hypoxia-mediated osteogenesis and bone
formation
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