ABSTRACT
@#Nosiheptide is a typical thiopeptide antibiotic displaying potent activity toward various drug-resistant strains of Gram-positive pathogens.Although nosiheptide lacks in vivo activity, and good water-solubility with a series of uncontrollable analogues, which may limit its clinical application, glycosylated analogues may overcome problem of low activity and may improve its druggability.In search of novel glycosylated nosiheptide producers, we applied a genome mining strategy that identified Actinoalloteichus sp.AHMU CJ021 that contains all genes required.However, despite the presence of a predicted glycosyltransferase, glycosylated derivatives of nosiheptide were not detected, after following one strain many compounds (OSMAC) strategy and heterologous expression of a regulatory protein NocP.Nevertheless, nosiheptide produced by this strain was remarkably pure, and further experiments were conducted to improve its production by optimization of the culture medium.Under optimal conditions, 58.73 mg/L nosiheptide was produced, representing an almost 6-fold improvement compared to the original fermentation medium.Therefore, we consider Actinoalloteichus sp.AHMU CJ021 a suitable potential candidate for industrial production of nosiheptide, which provides the basis for solving the problem of nosiheptide structural analogues.
ABSTRACT
Objective:To explore the clinical value of arterial partial pressure of carbon dioxide (PaCO 2) combined with Wells score in predicting acute pulmonary embolism (PE). Methods:Patients with suspected acute PE admitted to Emergency Department of Beijing Chaoyang Hospital, Capital Medical University from January 1, 2016 to August 31, 2021 were screened. Patients with positive computed tomography pulmonary angiography (CTPA) results were classified as the PE group, and those with negative CTPA results were classified as the non-PE group. Demographic characteristics, symptoms, vital signs, underlying diseases, risk factors for venous thrombosis, arterial blood gas analysis and Wells scores were statistically analyzed and compared between the two groups, and the clinical efficacy of PaCO 2 combined with Wells score in predicting acute PE was evaluated. Results:A total of 1 869 patients with suspected acute PE were screened, and 1 492 patients were finally selected. There were 537 cases in the PE group and 955 cases in the non-PE group. The frequency of chest pain, dyspnea, unilateral lower limb edema, history of PE or deep venous thrombosis, history of surgery or immobilization within 3 months, history of fracture within 3 months, active malignant tumor, elevated Wells score and reduced PaCO 2 in the PE group was significantly higher than that in the non-PE group (all P< 0.05). The area under receiver operating characteristic (ROC) curve (AUC) of Wells score was 0.784 (95% CI: 0.758-0.810), and the sensitivity and specificity of predicting acute pulmonary embolism were 61.64% and 88.48%, respectively. The AUC of reduced PaCO 2 was 0.679 (95% CI: 0.651-0.707), and the sensitivity and specificity of predicting acute pulmonary embolism were 79.89% and 55.92%, respectively. The AUC of reduced PaCO 2 combined with Wells score was 0.837 (95% CI: 0.816-0.858), and the sensitivity and specificity of predicting acute pulmonary embolism were 74.12% and 77.07%, respectively. The AUC of reduced PaCO 2 combined with Wells score was significantly greater than the AUC of Wells score ( P<0.001) and the AUC of reduced PaCO 2 ( P<0.001). Conclusions:The efficacy of PaCO 2 reduction combined with Wells score in predicting acute PE was superior to that of either of them alone. This was a beneficial supplement to the screening of patients with acute PE, and would also help reduce the abuse of CTPA in the emergency department.
ABSTRACT
<p><b>OBJECTIVE</b>To compare the toxicity on normal liver cells LO2 before and after Kansui Radix stir-baked with vinegar, and make a preliminary study on the mechanism of detoxication of Kansui Radix stir-baked with vinegar.</p><p><b>METHOD</b>The MTT method was adopted to detect the cell activity, with normal liver cells LO2 as the study object. The morphology of cells were observed, and the level or content of AST, ALT, LDH, SOD, Na+-K+-ATPase, Ca2+-Mg2+ -ATPase, GSH and MDA were determined in cell culture supernatant and splitting supernatant.</p><p><b>RESULT</b>Compared with the control group, Kansui can obviously inhibit the cell activity (P < 0.01) and morphology, and increase the levels of ALT, AST, and LDH (P < 0.01) in the supernatant fluid of cell incubation, and decrease the level of SOD and the content of GSH (P < 0.01). Besides, it significantly increased the content of MDA (P < 0.01) and significantly decreased the level of Na+-K+-ATPase and Ca2+-Mg2+ -ATPase (P < 0.01) in the supernatant fluid of cell dissociation. Compared with Kansui group of various doses, Kansui Radix stir-baked with vinegar can significantly decrease the cell proliferation inhibition and the trend of morphological variation, and obviously decrease the levels of ALT, AST, and LDH (P < 0.01) in the supernatant fluid of cell incubation, and significantly increase the level of SOD and the content of GSH (P < 0.01), and significantly decrease the content of MDA (P < 0.01). Additionally, it significantly increased the level of Na+-K+-ATPase and Ca2+-Mg2+ ATPase (P < 0.01) in the supernatant fluid of cell dissociation, and showed a certain dose-effect relationship.</p><p><b>CONCLUSION</b>Stir-baking with rice vinegar can release the hepatotoxicity of Kansui Radix. Its possible mechanism was that Kansui Radix stir-baked with vinegar can decrease the influence of Kansui Radix on the permeability of liver cells LO2 membrane and oxidative damage, in order to provide basis for further exploration of the detoxication mechanism of Kansui Radix stir-baked with vinegar.</p>
Subject(s)
Humans , Acetic Acid , Chemistry , Cell Line , Cell Proliferation , Chemistry, Pharmaceutical , Drugs, Chinese Herbal , Chemistry , Toxicity , Euphorbia , Chemistry , Liver , Cell Biology , Oxidative Stress , Plant Roots , Chemistry , Sodium-Potassium-Exchanging ATPase , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To analyze and identify the chemical ingredients in Sini San by LC-MS.</p><p><b>METHOD</b>These compounds were analyzed with an ACQUITY UPLC BEH C18 (2.1 mm x 100 mm, 1.7 microm) by gradient elution of methyl cyanides and 0.1% formic acid. ESI source was used and data were collected in positive and negative mode.</p><p><b>RESULT</b>Seventeen compounds of Sini San were identified by direct comparison in both positive and negative modes of Q-TOF-MS, the elemental compositions analysis, the standard substance and the data of the literature.</p><p><b>CONCLUSION</b>It is a rapid and accurate method that the composition of compound prescription of traditional Chinese medicine can be identified in terms of the separation of ultra high performance liquid chromatography, the accurate molecurlar weights measured by MS and other information, which can trace to the source of compounds in Sinisan.</p>