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Statistical modeling and optimization for enhanced hyaluronic acid production by batch culture of Sreptococcus

Long LIU, Haiquan YANG, Guocheng DU, Miao WANG, Jian CHEN,

《化学科学与工程前沿（英文）》 2009年第3卷第4期页码 351-356 doi: 10.1007/s11705-009-0248-8

摘要： This work is aimed to achieve the optimal hyaluronic acid (HA) production by batch culture of via the supplement of nucleotide bases using response surface methodology (RSM). First, the influence of nucleotide bases (adenine, guanine, cytosine, thymine, and uracil) on microbial HA production was investigated using fractional factorial design (FFD). By a 2 FFD, uracil was found to be the most significant factor for cell growth and HA production, while the other nucleotide bases were shown to have no significant effects on cell growth and HA production. Also, the impact of uracil on cell growth and HA production was further investigated by RSM, where two variables were considered: uracil concentration and supplement time. The optimal uracil concentration and supplement time were found to be 0.051g/L and 7h, respectively, and the predicted maximal HA production reached 6.42g/L. The maximal HA production increased from 5.0g/L of the control without uracil supplement to 6.31g/L at the optimal conditions in validation experiments.

关键词： control microbial HA thymine influence culture

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Bioactive hyaluronic acid fragments inhibit lipopolysaccharide-induced inflammatory responses via the

Na You, Sasa Chu, Binggang Cai, Youfang Gao, Mizhou Hui, Jin Zhu, Maorong Wang

《医学前沿（英文）》 2021年第15卷第2期页码 292-301 doi: 10.1007/s11684-020-0806-5

摘要： The high- and the low-molecular weight hyaluronic acids (HMW-HA and LMW-HA, respectively) showed different biological activities in inflammation. However, the role of LMW-HA in inflammatory response is controversial. In this study, we aimed to investigate the effect of bioactive hyaluronan (B-HA) on lipopolysaccharide (LPS)-induced inflammatory responses in human macrophages and mice. B-HA was produced from HA treated with glycosylated recombinant human hyaluronidase PH20. Human THP-1 cells were induced to differentiate into macrophages. THP-1-derived macrophages were treated with B-HA, LPS, or B-HA+LPS. The mRNA expression and the production of inflammatory cytokines were determined using quantitative real-time PCR and enzyme-linked immunosorbent assay. The phosphorylation levels of proteins in the nuclear factor- B (NF- B), mitogen-activated protein kinase (MAPK), and IRF-3 signaling pathways were measured using Western blot. The efficacy of B-HA was assessed in a mouse model of LPS-induced inflammation. Results showed that B-HA inhibited the expression of TNF-α, IL-6, IL-1, and IFN-β, and enhanced the expression of the anti-inflammatory cytokine IL-10 in LPS-induced inflammatory responses in THP-1-derived macrophages and . B-HA significantly suppressed the phosphorylation of the TLR4 signaling pathway proteins p65, IKKα/β, I Bα, JNK1/2, ERK1/2, p38, and IRF-3. In conclusion, our results demonstrated that the B-HA attenuated the LPS-stimulated inflammatory response by inhibiting the activation of the TLR4 signaling pathway. B-HA could be a potential anti-inflammatory drug in the treatment of inflammatory disease.

关键词： bioactive hyaluronan lipopolysaccharide inflammatory cytokines TLR4 human macrophages

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Paeoniflorin prevents hepatic fibrosis of by inhibiting TGF-β1 production from macrophages in mice

CHU Deyong, LI Conglei, SHEN Jilong, WU Qiang

《医学前沿（英文）》 2008年第2卷第2期页码 154-165 doi: 10.1007/s11684-008-0029-7

摘要： In order to investigate the effect of paeoniflorin (PAE) on hepatic fibrosis of mice with and , a model of hepatic fibrosis caused by schistosomiasis was established in mice infected with cercariae of . Then, PAE was orally administered before and after praziquantel treatment and both therapeutics were given simultaneously at different time points after the infection. The concentration of serum hyaluronic acid (HA) was determined by radioimmunoassay (RIA). Hepatic granuloma and fibrosis were evaluated via HE and Masson staining. The expression of ?-smooth muscle actin (?-SMA), transforming growth factor ?1 (TGF-?1) and collagen I (Col I) protein was detected by immunohistochemistry. The effect of soluble egg antigen (SEA) and PAE on the production of TGF-?1 from mouse peritoneal macrophages (PM?s) was investigated by RT-PCR, Western blotting and ELISA. The effect of TGF-?1 in optimum macrophage-conditioned medium (OPMCM) on the proliferation of hepatic stellate cells (HSCs) and collagen secretion from HSCs with anti-TGF-?1 antibody was explored by MTT assay and ELISA. The results show that PAE could significantly reduce the concentration of serum HA, the size of egg granuloma, the severity of hepatic fibrosis and the expression of ?-SMA, TGF-?1 and Col I protein in the pre-treatment group. However, in sim- or post-treatment group, PAE did not have any significant therapeutic effect. TGF-?1 could be secreted from PM?s stimulated by SEA. Meanwhile, the production of TGF-?1 from PM?s could be depressed significantly by PAE in a concentration-dependent manner. TGF-?1 could promote the proliferation of HSCs and the secretion of collagens. In a word, PAE can prevent hepatic granuloma and fibrosis caused by schistosomiasis japonica through the inhibition of the secretion of TGF-?1 from PM?s, the proliferation and activation of HSCs and the secretion of collagens from HSCs.

关键词： cercariae collagen hyaluronic OPMCM soluble