Nonalcoholic fatty liver disease (NAFLD) is a hepatic ailment with a rapidly increasing incidence in the human population due largely to dietary hyper nutrition and subsequent obesity. Discovering effective natural compounds and herbs against NAFLD can provide alternative and complementary medical treatments to current chemical pharmaceuticals. In this study, ICR male mice were fed a high-fat diet (HFD) in vivo and the AML12 cells were treated with palmitic acid (PA) in vitro. We explore the protective effect and potential mechanism of Chinese Herbal Formula (CHF03) against NAFLD by HE staining, transmission Electron Microscopy assay, Western blotting, and gene expression. In vivo, oxidative stress markers (GSH, GSH-px, MDA, SOD, and CAT) confirmed that CHF03 alleviated oxidative stress and abundance of NF-κB proteins indicating a reduction in inflammation and oxidative stress. The lower protein abundance of ACACA and FASN indicated a preventive effect on lipogenesis. Histological and ultrastructural observations revealed that CHF03 inhibited NAFLD. Expression of Srebf1, Fasn, and Acaca, which are associated with lipogenesis, were downregulated. In vitro, genes and proteins are expressed in a dose-dependent manner, consistent with those in the liver. CHF03 inhibited lipid accumulation and expression of NF-κB, nuclear transfer, and transcriptional activity in AML12 cells. The CHF03 might have a beneficial role in the prevention of hepatic steatosis by altering the expression of lipogenic genes and attenuating oxidative stress.
In this paper, we investigate the group consensus for leaderless multi-agent systems. The group consensus protocol based on the position information from neighboring agents is designed. The network may be subjected to frequent cyber-attacks, which is close to an actual case. The cyber-attacks are assumed to be recoverable. By utilizing algebraic graph theory, linear matrix inequality (LMI) and Lyapunov stability theory, the multi-agent systems can achieve group consensus under the proposed control protocol. The sufficient conditions of the group consensus for the multi-agent networks subjected to cyber-attacks are given. Furthermore, the results are extended to the consensus issue of multiple subgroups with cyber-attacks. Numerical simulations are performed to demonstrate the effectiveness of the theoretical results.
This paper studies the node‐to‐node consensus problem for multi‐agent networks possessing a leaders' layer and a followers' layer via the pinning control. In order to realize the consensus and reduce the update frequency of the controller, a suitable event‐triggered mechanism is introduced into the control strategy. Furthermore, the phenomenon of packet loss is considered in the designed controller. Based on the M‐matrix theory and Lyapunov stability theory, this paper presents the sufficient conditions for the node‐to‐node consensus of networks. Meanwhile, it is proved that the Zeno behaviour is excluded. Finally, two numerical simulations are provided to demonstrate the effectiveness of the theoretical results.
Friedelin, the most rearranged pentacyclic triterpene, also exhibits remarkable pharmacological and anti-insect activities. In particular, celastrol with friedelin as the skeleton, which is derived from the medicinal plant Tripterygium wilfordii, is a promising drug due to its anticancer and antiobesity activities. Although a previous study achieved friedelin production using engineered Saccharomyces cerevisiae, strains capable of producing high-level friedelin have not been stably engineered. In this study, a combined strategy was employed with integration of endogenous pathway genes into the genome and knockout of inhibiting genes by CRISPR/Cas9 technology, which successfully engineered multiple strains. After introducing an efficient TwOSC1T502E, all strains with genetic integration (tHMG1, ERG1, ERG20, ERG9, POS5, or UPC2.1) showed a 3.0∼6.8-fold increase in friedelin production compared with strain BY4741. Through further double knockout of inhibiting genes, only strains GD1 and GD3 produced higher yields. Moreover, strains GQ1 and GQ3 with quadruple mutants (bts1; rox1; ypl062w; yjl064w) displayed similar increases. Finally, the dominant strain GQ1 with TwOSC1T502E was cultured in an optimized medium in shake flasks, and the final yield of friedelin reached 63.91 ± 2.45 mg/L, which was approximately 65-fold higher than that of the wild-type strain BY4741 and 229% higher than that in ordinary SD-His-Ura medium. It was the highest titer for friedelin production to date. Our work provides a good example for triterpenoid production in microbial cell factories and lays a solid foundation for the mining, pathway analysis, and efficient production of valuable triterpenoids with friedelin as the skeleton.
Panax notoginseng is one of the
most famous valuable medical plants in China, and its broad application
in clinical treatment has an inseparable relationship with the active
molecules, ginsenosides. Ginsenosides are glycoside compounds that
have varied structures for the diverse sugar chain. Although extensive
work has been done, there are still unknown steps in the biosynthetic
pathway of ginsenosides. Here, we screened candidate glycosyltransferase
genes based on the previous genome and transcriptome data of P. notoginseng and cloned the full length of 27 UGT
genes successfully. Among them, we found that PnUGT33
could catalyze different ginsenoside substrates to produce higher
polarity rare ginsenosides by extending the sugar chain. We further
analyzed the enzymatic kinetics and predicted the catalytic mechanism
of PnUGT33 by simulating molecular docking. After
that, we reconstructed the biosynthetic pathway of rare ginsenoside
Rg3 and gypenoside LXXV in yeast. By combining the Golden
Gate method and overexpressing the UDPG biosynthetic genes, we further
improved the yield of engineering yeast strain. Finally, the shake-flask
culture yield of Rg3 reached 51 mg/L and the fed-batch
fermentation yield of gypenoside LXXV reached 94.5 mg/L, which was
the first and highest record.
Objective To investigate Changweishu’s clinical effect on gastrointestinal dysfunction in patients with sepsis. Methods Fifty patients with gastrointestinal dysfunction and sepsis were randomly divided into treatment and control groups. The control group patients received routine Western medicine treatments (meropenem, noradrenaline, glutamine glue, Bifidobacterium lactis triple-strain tablet), and the treatment group patients received routine Western medicine treatment combined with Changweishu. Treatments in both groups lasted 7 days. Changes in APACHE II score, gastrointestinal dysfunction score, serum levels of diamine oxidase (DAO), D-lactic acid, inflammatory factors (tumor necrosis factor (TNF)-α, interleukin (IL)-6, and high-mobility group box 1 (HMGB-1)), and the incidence of multiple organ dysfunction syndrome (MODS) and mortality were observed. Results After treatment, APACHE II score, gastrointestinal dysfunction score, and DAO, D-lactic acid, TNF-α, IL-6, and HMGB-1 levels decreased significantly in both groups, but the decrease was more significant in the treatment group than in the control group. The incidence of MODS and mortality were significantly lower in the treatment group than in the control group. Conclusion The addition of Changweishu to routine Western treatments can improve gastrointestinal function in patients with sepsis and gastrointestinal dysfunction, as well as decreasing the incidence of MODS and mortality and improving patient prognosis.
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