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Exp Ther Med ; 18(6): 4811-4819, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31798707


The production of lactate under hypoxic conditions or by cancer cells was reported to promote the M2 polarization of tumor-associated macrophages. However, the exact effect of lactate on macrophages, particularly under hypoxic conditions, has remained largely elusive. In the present study, an in-depth bioinformatics analysis of previously published transcriptome data of macrophages was performed. A total of 6, 101 and 764 upregulated genes were identified in the lactate, hypoxia and hypoxia-lactate groups, respectively, whereas 4, 41 and 588 genes were downregulated in the same respective groups. Furthermore, differentially expressed genes (DEGs) of the hypoxia and hypoxia-lactate groups were significantly enriched in the hypoxia-inducible factor 1 (HIF-1) signaling pathway and the Hedgehog pathway. Upregulation of the mTOR and Hedgehog pathways in the hypoxia-lactate group was identified by gene set enrichment analysis. Furthermore, a set of HIF-1 pathway-associated genes was identified to be positively correlated with hypoxia using weighted gene co-expression network analysis. Lactate was indicated to inhibit the cell cycle in a hypoxia-independent manner. The DEGs of the hypoxia and hypoxia-lactate groups, including C-C motif chemokine receptor type 1 and 5, were enriched in the cytokine-cytokine receptor interaction pathway. In conclusion, under normoxic conditions, lactate exerted a weak effect on macrophages, while the combination of lactate and hypoxia markedly promoted the M2-polarization of macrophages via the HIF-1, Hedgehog and mTOR pathways. Lactate and hypoxia may also contribute to the formation of the spatial structure of tumor niches by inhibiting the proliferation of resident macrophages and by regulating the recruitment of peripheral macrophages.

Int J Biol Macromol ; 62: 291-5, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24012699


Water-soluble polysaccharides (DCCP, DCPP) were extracted from the stems of Dendrobium chrysotoxum using boiling water and ultrasound. DCPP were successively purified by chromatography on DEAE-Cellulose-52 and Sephadex G-200 column, giving three major polysaccharide fractions termed DCPP-I, DCPP-I-a and DCPP-II. Among these fractions, DCPP-I-a exhibited the highest abundance (79.5%). The number-average molecular weight and weight-average molecular weight of DCPP-I-a were 67 kDa and 122 kDa, respectively. Monosaccharide components analysis indicated that DCPP-I-a were composed of xylose, glucose, galactose in a molar ratio of 1.44:6.93:12.79. Infrared spectra (IR) and (1)H NMR showed that DCPP-I-a was composed of a ß-D pyran ring with a ß-configuration. The evaluation of anti-proliferation activity suggested that DCPP-I-a and DCPP-II had a higher inhibitory effect on the SPC-A-1 cells than DCCP as determined with in vitro anti-proliferation test.

Dendrobium/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Peso Molecular , Monossacarídeos/análise , Polissacarídeos/isolamento & purificação