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Wang Qi,Dai Huajie,Hou Tianzhichao,Hou Yanan,Wang Tiange,Lin Hong,Zhao Zhiyun,Li Mian,Zheng Ruizhi,Wang Shuangyuan,Lu Jieli,Xu Yu,Liu Ruixin,Ning Guang,Wang Weiqing,Bi Yufang,Zheng Jie,Xu Min 대한뇌졸중학회 2023 Journal of stroke Vol.25 No.3
Background and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). Methods We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. Results Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, <i>Bifidobacteriales</i> order, <i>Bifidobacteriaceae</i> family, <i>Desulfovibrio</i> genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all <i>P</i><0.044). The causal associations between <i>Bifidobacteriales</i> order, <i>Bifidobacteriaceae</i> family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas <i>Desulfovibrio</i> genus was negatively associated with ApoB/ApoA1 (all <i>P</i><0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between <i>Bifidobacteriales</i> order, <i>Bifidobacteriaceae</i> family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (<i>P</i>=0.028) and 4.6% (<i>P</i>=0.033); the association between <i>Desulfovibrio</i> genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (<i>P</i>=0.019), 4.2% (<i>P</i>=0.035), and 9.1% (<i>P</i>=0.013), respectively. Conclusion The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.
( Xue Wang ),( Qiao-li Yang ),( Yu-zhu Shi ),( Bi-yu Hou ),( Sheng-qian Yang ),( Hua Huang ),( Li Zhang ),( Guan-hua Du ) 한국미생물생명공학회(구 한국산업미생물학회) 2017 Journal of microbiology and biotechnology Vol.27 No.9
Viola tianshanica Maxim, belonging to the Violaceae plant family, is traditionally used in Uighur medicine for treating pneumonia, headache, and fever. There is, however, a lack of basic understanding of its pharmacological activities. This study was designed to observe the effects of the ethanol extract (TSM) from Viola tianshanica Maxim on the inflammation response in acute lung injury (ALI) induced by LPS and the possible underlying mechanisms. We found that TSM (200 and 500 mg/kg) significantly decreased inflammatory cytokine production and the number of inflammatory cells, including macrophages and neutrophils, in bronchoalveolar lavage fluid. TSM also markedly inhibited the lung wet-to-dry ratio and alleviated pathological changes in lung tissues. In vitro, after TSM (12.5-100 μg/ml) treatment to RAW 264.7 cells for 1 h, LPS (1 μg/ml) was added and the cells were further incubated for 24 h. TSM dose-dependently inhibited the levels of proinflammatory cytokines, such as NO, PGE<sub>2</sub>, TNF-α, IL-6, and IL-1β, and remarkably decreased the protein and mRNA expression of TNF-α and IL-6 in LPS-stimulated RAW 264.7 cells. TSM also suppressed protein expression of p-IκBa and p-ERK1/2 and blocked nuclear translocation of NF-κB p65. The results indicate that TSM exerts anti-inflammatory effects related with inhibition on NF-κB and MAPK (p-ERK1/2) signaling pathways. In conclusion, our data demonstrate that TSM might be a potential agent for the treatment of ALI.