Effect of Doxycycline on Intrinsic Apoptosis of Myeloma Cell Line H929 and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the mechanism of the in vitro toxicity of doxycycline to myeloma cell line H929 and also the possible pathway involved its toxicity.@*METHODS@#Myeloma cell line H929 was treated with DOX, MEK inhibitor U0126 or RAS agonist ML-098, either alone or in combination. Then, the expression of p-MEK, caspase-3, caspase-9 and c-Jun in H929 were used to detected by Western blot; the cells proliferation and apoptosis were detected by CCK-8 assay and flow cytometry, respectively.@*RESULTS@#DOX significantly increased the levels of cleaved caspase-3 and caspase-9, and down-regulated the level of p-MEK in H929 (P<0.05). MEK antagonist U0126 significantly increased the levels of cleaved caspase-3 and caspase-9, and down-regulated the level of p-MEK (P<0.05). After Dox combined with ML-098 treatment of H929 cells, the apoptosis rate of H929 cells was lower than that of DOX alone treatment group(P<0.05). Compared with DOX alone treatment group, the expressions of p-MEK and p-ERK1/2 in DOX+ML-098 combined treatment group were increased, and the levels of cleaved caspase-3,9 in H929 cells were decreased (P<0.05). The levels of c-Jun mRNA and protein increased in H929 when treated by DOX alone (P<0.05).@*CONCLUSION@#DOX can induce apoptosis of H929 via intrinsic apoptosis pathway, and MEK/ERK pathway and c-Jun possibly play a role in this process.

Gut flora and gut-derived endotoxin in minimal hepatic encephalopathy / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the relationship of gut flora and gut-derived endotoxin with minimal hepatic encephalopathy (MHE).</p><p><b>METHODS</b>Patients with hepatitis B virus-related liver cirrhosis (HBV-LC) were screened for MHE using the number connect test-A (NCT-A) and digital symbol test (DST) and divided into the following groups: HBV-LC with (+) MHE (n = 26) and HBV-liver cirrhosis without (-) MHE (n = 25); in addition, one healthy immediate family member of each patient in the HBV-LC + MHE group was enrolled as a control. Each participant provided fecal and blood samples. PCR amplification and 454 pyrosequencing were used to detect bacterial 16S rRNA in feces. Turbidimetric Limulus amebocyte lysate assay was used to detect level of endotoxin in serum. The significance of inter-group differences was assessed by one-way ANOVA or Student's t-test.</p><p><b>RESULTS</b>The three groups showed different distributions of gut flora. The differences in the microbial communities' members and distributions were related to disease or health status, but not to the patient's genetic makeup or diet. In particular, the HBV-LC + MHE patients showed significantly lower amounts of different bacterial species and abundance of these species than the other two (non-MHE) groups (P less than 0.05). The healthy control family members had a richer diversity of gut flora than their counterparts with HBV-LC + MHE (P less than 0.05). The HBV-LV + MHE patients also had higher serum levels of endotoxin.</p><p><b>CONCLUSION</b>Development of minimal hepatic encephalopathy in patients with HBV-LC may be related to a gut flora disorder or higher levels of endotoxin in serum.</p>