Gastric cancer-derived exosomes facilitate pulmonary metastasis by activating ERK-mediated immunosuppressive macrophage polarization.

Gastric cancer (GC) with pulmonary metastasis is one of the deadliest diseases in the world; however, the underlying pathological mechanisms and potential therapeutic targets remain to be elucidated. As exosomes play indispensable roles in the formation of premetastatic niches (PMN) and cancer metastasis. Therefore, investigating the underlying mechanisms of exosome-mediated pulmonary metastasis of GC may shed new light on identifying novel therapeutic targets for GC treatment. GC-derived exosomes were isolated from the conditioned medium of mouse forestomach carcinoma (MFC) cell line. The effects of MFC-derived exosomes on pulmonary macrophage polarization were analyzed by reverse- transcription polymerase chain reaction and flow cytometry. Expression of PD-L1 and other proteins was evaluated by Western blot. Exosomal microRNAs (miRNAs) were analyzed by microarray. GC-derived exosomes (GC-exo) accumulated in high numbers in the lungs and were ingested by macrophages. The extracellular-signal-regulated kinase (ERK) signaling pathway was activated by GC-exo, inducing macrophage immunosuppressive-phenotype differentiation and increased PD-L1 expression. miRNA-sequencing identified 130 enriched miRNAs in GC-exo. Among the enriched miRNAs, miR-92a-3p plays a major role in activating ERK signaling via inhibition of PTEN expression. In addition, inhibiting ERK signaling with PD98059 significantly reduced the expression of PD-L1 in macrophages and, therefore, reversed the immunosuppressive PMN and inhibited the colonization of GC cells in the lungs. This study identified a novel mechanism of GC-exo mediated PD-L1 expression in lung macrophages that facilitates lung PMN formation and GC pulmonary metastasis, which also provided a potential therapeutic target for GC with pulmonary metastasis treatment.

[Effect of forchlorfenuron on fruit morphology and lignans content of Schisandra chinensis].

The effect of plant growth regulator forchlorfenuron (CPPU) 1 x 10(-6), 0.67 x 10(-6), 0.5 x 10(-6) on fruit morphology and effective components lignans was studied. Those morphologies were the combination of four basic morphological changes. The result showed, diametre were increased and longitudinal diametre of fruits were inhibited by foliage fertilizers including CPPU. At the same time, 1 000-grain weight and yield showed the varying degrees increase under CPPU. The order of the degree was 0.5 x 10(-6) > 1 x 10(-6) > 0.67 x 10(-6). Six lignans content of Schisandra chinensis of different harvest time and different CPPU processing groups were determined, the results showed that lignans accumulation occurred mainly in periods of premature the half mature fruiting stages. Under the 0.67 x 10(-6) CPPU treatment, schisandrol B, schisandrin B, schisandrin C content of S. chinensis showed different increase.

[Identification of Schisandra chinensis with white fruits based on ITS2 sequences].

OBJECTIVE: To analyse a special kind of Schisandra chinensis with the white fruit using ITS2 barcode at molecular levels. METHOD: ITS2 regions were sequenced bidirectionally. Sequence assembly and consensus sequence generation were performed using the CodonCode Aligner, MEGA 5.0 software was used to align the sequences. The ITS2 secondary structure was predicted using ITS2 web server, BLAST 1 method was used to identify the S. chinensis with the white fruit. RESULT: The length of the ITS2 sequence was 231 bp. And the sample was identified as S. chinensis using the method of BLAST 1. Their mean interspecific genetic distance (K2P distance) among the populations of the S. chinensis with the white fruit and S. chinensis was far lower than the mean interspecific genetic distance between the S. chinensis and S. sphenanthera. CONCLUSION: By using ITS2 the S. chinensis with the white fruit was identified as S. chinensis, and the ITS2 barcode could be used to identify S. chinensis and S. sphenanthera.

[HPLC determination of six lignans in different parts of Schisandra chinensis].

OBJECTIVE: To compare the content of six lignans of different parts of Schisandra chinensis. METHOD: Agilent TC-C18 (4.6 mm x 250 mm, 5 microm) was used with acetonitrile-water gradient system as mobile phase. Wave length was 250 nm. The flow rate was 1 mL x min(-1). Column temperature was 30 degrees C. RESULT: The total lignans content of wild Schisandra chinensis was higher than that of the cultivated varieties. The total lignans content of different parts varied significantly, wherein the root > main branch > side branches > leaf. CONCLUSION: This method is stable, reliable, can be used for the quality evaluation of different parts of Schisandra.