Identification of a new C-23 metabolite in sterol degradation of Mycobacterium neoaurum HGMS2 and analysis of its metabolic pathways / 生物工程学报

Mycobacterium neoaurum has the ability to produce steroidal intermediates known as 22-hydroxy-23, 24-bisnorchol-4-en-3-one (BA) upon the knockout of the genes for either the hydroxyacyl-CoA dehydrogenase (Hsd4A) or acyl-CoA thiolase (FadA5). In a previous study, we discovered a novel metabolite in the fermentation products when the fadA5 gene was deleted. This research aims to elucidate the metabolic pathway of this metabolite through structural identification, homologous sequence analysis of the fadA5 gene, phylogenetic tree analysis of M. neoaurum HGMS2, and gene knockout. Our findings revealed that the metabolite is a C23 metabolic intermediate, named 24-norchol-4-ene-3, 22-dione (designated as 3-OPD). It is formed when a thioesterase (TE) catalyzes the formation of a β-ketonic acid by removing CoA from the side chain of 3, 22-dioxo-25, 26-bisnorchol-4-ene-24-oyl CoA (22-O-BNC-CoA), followed by spontaneously undergoing decarboxylation. These results have the potential to contribute to the development of novel steroid intermediates.

Curative efficacy and safety of Kangfuxin liquid in treating patients of upper gastrointestinal hemorrhage caused by non-steroid drugs treated with somatostatin / 中国免疫学杂志

Objective:To investigate the curative efficacy and safety of Kangfuxin liquid in treating patients of upper gastrointestinal hemorrhage caused by non-steroid drugs treated with somatostatin.Methods:90 patients with upper gastrointestinal hemorrhage caused by non-steroid drugs meeting the inclusion criteria were collected as observational objects to be randomly divided into the control group and the observation group with 45 cases in each group.Besides conventional treatments,the control group was given somatostatin,while the observation group was given Kangfuxin liquid in combination with somatostatin.Then,the curative efficiency,hemostatic time,recurrent bleeding rate,levels of serum inflammatory factors and adverse reactions were observed and compared.Results:Assessment of curative efficacy showed that the total therapeutic efficiency ratio in the observation group was statistically higher than that in the control group(95.6％ vs 82.2％,P＜0.05).In comparison with the control group,the hemostatic time in the observation group was statistically shorter[(1.4±0.5)d vs (2.6±0.7)d,P＜0.05],while the recurrent bleeding rate in the two groups was statistically same(4.4％ vs 11.1％,P＞0.05).As to inflammatory factors,the observation group had statistically lower levels of serum TNF-α and IL-6 than those in the control group [(5.46±0.93)ng/L vs (8.37± 1.08)ng/L,(19.37±3.43)ng/L vs (38.22±8.14)ng/L,both P＜0.05].During the treatment,there was no case of severe adverse reactions.And the incidences of adverse reactions in the observation group and the control group were statistically same (22.2％ vs 15.6％,P＞0.05).Conclusion:Besides treatment of somatostatin,adjuvant therapy of Kangfuxin liquid has well application effect in patients of upper gastrointestinal hemorrhage caused by non-steroid drugs.And it can significantly increase curative efficacy,shorten hemostatic time,alleviate inflammatory reaction with minor adverse reactions.