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Fusidane-type antibiotics, represented by helvolic acid, fusidic acid and cephalosporin P
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Biotransformation of α-asarone by Alternaria longipes CGMCC 3.2875 yielded two pairs of new neolignans, (+) (7S, 8S, 7'S, 8'R) iso-magnosalicin (1a)/(-) (7R, 8R, 7'R, 8'S) iso-magnosalicin (1b) and (+) (7R, 8R, 7'S, 8'R) magnosalicin (2a)/(-) (7S, 8S, 7'R, 8'S) magnosalicin (2b), and four known metabolites, (±) acoraminol A (3), (±) acoraminol B (4), asaraldehyde (5), and 2, 4, 5-trimethoxybenzoic acid (6). Their structures, including absolute configurations, were determined by extensive analysis of NMR spectra, X-ray crystallography, and quantum chemical ECD calculations. The cytotoxic activity and Aβ
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Organic carbonates (OCs) are a class of compounds featured by a carbonyl flanked by two alkoxy/aryloxy groups. They exist in either linear or cyclic forms, of which the majority encountered in nature adopt a pentacyclic structure. However, the enzymatic basis for pentacyclic carbonate ring formation remains elusive. Here, we reported that a four-protein metabolon (AlmUII-UV) assembled by a small peptide protein (AlmUV) appends a reactive
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An eco-friendly and fast HPLC method was developed for the determination of adenosine, inosine, guanosine and uridine in Cordyceps and related products (fermented mycelia of Hirsutella sinensis andPaecilomyces hepiali). The sample was ultrasonically extracted using 0.5% phosphoric acid solutions for 2.5 min. Sample separation was performed on a Poroshell SB-Aq column (50 mm × 4.6 mm, 2.7 μm) using eco-friendly mobile phase consisting of formic acid and ammonium formate aqueous solution at a flow rate of 1.0 mL·min
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Adenosine , Chromatography, High Pressure Liquid , Cordyceps , NucleosidesABSTRACT
A chemical investigation on
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Objective:To summarize the development of a patient with complex regional pain syndrome (CRPS) after distal radius fracture and the effect of repetitive transcranial magnetic stimulation (rTMS) combined with conventional rehabilitation on it. Methods:One patient with CRPS after left distal radius fracture was treated with rTMS combined with conventional rehabilitation for three weeks. The pain degree was evaluated with Visual Analogue Score (VAS), the edema was assessed with volume of hand and circumference of finger, and motion of joint was measured with passive range of motion. The activities of daily living was assessed with modified Barthel Index (MBS). Results:Before treatment, the VAS score was 8, the volume of left hand was 330 ml, the temperature of skin was 36.8 ℃. The activity of flexion and extension of left elbow joint, pronation and supination of left forearm, the flexion, extension, ulnar deviation and temporal deviation of left wrist, and metacarpophalangeal joints (MCP), proximal interphalangeal joint (PIP) and distal interphalangeal joint (DIP) of left hand were all limited. The circumference of left finger was larger than right finger, and the score of MBI was 85. After three weeks of treatment, the VAS score was 2, the volume of the left hand was 310 ml, the temperature of the skin was 33.8 ℃. The activities of left elbow joint, left wrist joint and left MCP, PIP, and DIP were better than before. The score of MBI was 100. Conclusion:rTMS combined with conventional rehabilitation is effective on CRPS after distal radius fracture, in the range of motion and edema of upper extremity, and activities of daily living.
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, a widely used Chinese herbal medicine, was considered as central nervous system (CNS) drug for years. Both ethanol extracts (EES) and water extracts (WES) of it were applied clinically. Unfortunately, the difference of their efficacy and even effective material foundation of remains obscure. In this study, to explore the active constituents of , we compared pharmacodynamics and chemical profiles / of EES/WES for the first time using multiple chemical analysis, pharmacological and data processing approaches. It was proved that there was no significant difference in the anti-depressive effects between WES and EES. However, the contents of most components and in plasma were higher in EES than those in WES, which was unconvincing for their similar efficacy. Therefore, we further explored components of targeted onto brain and the results showed that 5 lignans were identified with definite absorptivity respectively both in EES and WES caused by the limitation of blood-brain barrier. Moreover, bioinformatic analysis predicted their anti-depressive action. Above all, the systematic strategy screened 5 brain-targeted effective substances of and it was suggested that exploring the components into nidi would promote the studies on herbs effective material basis.
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A pair of new tirucallane triterpenoid epimers, picraquassins M and N (1> and 2), were isolated from the stems of Picrasma quassioides (D. Don) Benn. Their structures were determined based on comprehensive spectroscopic and X-ray crystallographic analyses. In addition, their AChE inhibitory activity, cytotoxicity against five human tumour cell lines (SW480, MCF-7, HepG2, Hela, and PANC-1), and antimicrobial activity against two bacteria (Staphylococcus. aureus 209P and Escherichia coli ATCC0111) and two fungi (Candida albicans FIM709 and Aspergillus niger R330) were evaluated.
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Objective:To analyze the known mechanism of toxicology and predict the unknown toxicity in Asari Radix et Rhizoma sinensis by establishing the network relationship of compound, protein, gene and toxicant reaction. Method:After comparing the Asari Radix et Rhizoma candidate compounds obtained from the traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database and the toxicological information obtained from the Comparative Toxicogenomics Database(CTD) database, we screened out 13 toxic components from Asari Radix et Rhizoma. And use the Pharm Mapper Server website to find the detailed information of target proteins of the 13 components. The network structure of these 13 chemical components and their corresponding target proteins were drawn by using Cytospace software, and several target proteins with the highest degree of association were found. ClueGO+CluePedia plug-in of Cytospace software was applied in gene ontology(GO) enrichment analysis of genes and kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis, so as to determine the pathways through which toxic substances in Asari Radix et Rhizoma might be harmful to human body. Result:The toxic substances in Asari Radix et Rhizoma may induce tumor and cancer formation through p53 signaling pathway, interleukin(IL)-17 signaling pathway, nuclear factor(NF)-kappa B signaling pathway, tumor necrosis factor(TNF)-signaling pathway. Asari Radix et Rhizoma could inhibit the central nervous system by regulating apoptosis pathways and neurons, and may also cause other autoimmune diseases by IL-17, TNF-α pathway and apoptosis regulation. Conclusion:This study preliminarily explores related mechanisms of toxicity of Asari Radix et Rhizoma,this method can be used to predict toxicity and explain toxicity mechanism of traditional Chinese medicine.
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Objective: To explore the mechanism of renal toxicity of Tripterygii Radix et Rhizoma by establishing the active component-target, protein interaction, biological function and pathway network corresponding to the target, and using molecular docking technology. Method: The traditional Chinese medicine(TCM) systems pharmacology database(TCMSP) and the comparative toxicogenomics database (CTD) were used to screen The toxic candidate compounds.In PubChem database, convert all candidate compounds into standard Canonical SMILES format, SMILES format file import SwissTargetPrediction platform, target prediction, will be the target of the corresponding compounds in TCMSP supplement with uniprot converts protein antipodal gene name, and from the human genome database (GeneCards) seek to compare the renal related gene protein,overlapping proteins were screened as potential renal toxicity targets of Tripterygii Radix et Rhizoma.Cytoscape software was used to construct the candidate components-target network of Tripterygii Radix et Rhizoma.Cytoscape software was combined with String database to draw the protein interaction network, DAVID platform was used to analyze the biological function of the target and the pathways involved, and Glide software was used to verify the combination of the key protein and the candidate components of tripterygiumwildiitoxicity. Result: The screening of 30 kinds of candidates for toxic ingredients of Tripterygii Radix et Rhizoma, involving 209 renal toxicity targets, network analysis results showed that Tripterygii Radix et Rhizoma by amino acid metabolism,phospholipid metabolism, catecholamine metabolism, inhibiting renal organic anion transporter Oatl, Oat2, Oat3 function, and inducing apoptosis, and participate in the mitogen-activated protein kinase(MAPK) signaling pathways, JAK-STAT signaling pathway,vascular endothelial growth factor(VEGF)signaling pathways,Toll-like receptor signaling pathway,ERBB signaling pathway, FcεRI signaling pathway, peroxisome proliferators-activated receptors(PPAR) signaling pathway such as toxic to the kidneys. Conclusion: The mechanism of kidney toxicity of Tripterygii Radix et Rhizoma was explored by using the characteristics of multi-component, multi-target and multi-pathway of TCM, which provided new ideas and methods for further research on the mechanism of kidney toxicity of Tripterygii Radix et Rhizoma.
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Objective:The mechanism of action of cardiac toxicity of Radix Aconiti Agrestis was explored by establishing the active components-targets network of Radix Aconiti Agrestis, protein interaction network, the biological function and pathway network of targets, and using molecular docking technology. Methods:The Traditional Chinese Medicine Systems Pharmacology(TCMSP) database and the Comparative Toxicogenomics Database(CTD) were used to filtrate the toxic candidates of Radix Aconiti Agrestis. Predicting the functional targets of toxic candidates of Radix Aconiti Agrestis by PharmMapper and compared with the cardiac related gene proteins found in the human gene database (GeneCards), and the overlapping proteins were selected as potential cardiac toxicity targets of Radix Aconiti Agrestis. The Cytoscape software was used to construct the network between toxic candidate components and targets. The protein interaction network was mapped by the String database combined with Cytoscape software. The biological functions of the targets and the involved pathways were analyzed with the DAVID platform.The binding of the key proteins with certain toxic candidate components of Radix Aconiti Agrestis was verified by Discover Studio software finally. Results:There were six candidates for toxic ingredients, which involving 27 cardiac toxicity targets. Network analysis results show that the targets were mainly by participating in the heart of phosphorus metabolism, regulation and other related phosphorus metabolism and regulation of phosphorylation and FKBP1A,TGF4-β2, INSR targets to have an important impact on the metabolism,development and form of the heart,and further to have cardiac toxicity. Conclusion:Based on the characteristics of the multi-component, multi-target and multi-pathway of traditional Chinese medicine, the mechanism of cardiac toxicity of Radix Aconiti Agrestis was explored and its possible toxicity was predicted, which provided a new idea and method for further research on the mechanism of cardiac toxicity of Radix Aconiti Agrestis.
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Fusidic acid is the only fusidane-type antibiotic that has been clinically used. However, biosynthesis of this important molecule in fungi is poorly understood. We have recently elucidated the biosynthesis of fusidane-type antibiotic helvolic acid, which provides us with clues to identify a possible gene cluster for fusidic acid ( cluster). This gene cluster consists of eight genes, among which six are conserved in the helvolic acid gene cluster except and . Introduction of the two genes into the NSAR1 expressing the conserved six genes led to the production of fusidic acid. A stepwise introduction of and revealed that the two genes worked independently without a strict reaction order. Notably, we identified two short-chain dehydrogenase/reductase genes and in the cluster, which showed converse stereoselectivity in 3-ketoreduction. This is the first report on the biosynthesis and heterologous expression of fusidic acid.
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<p><b>OBJECTIVE</b>To investigate the safety and efficacy of high dose tigecycline for treatment of fibric neutrope-nia in acute leukemia patients after ineffectiveness of carbapenems chemotherapy of acute leukemia.</p><p><b>METHODS</b>The clinical data of 41 acute leukemia patients with febrile ncutropenia received high dose tigecycline (100 mg q12h), who showed ineffectiveness of treatment with carbapenems, from 20151.30-2017.1. 29 in our hospital were collected and analyzed retrospectively. The temperature, inflammatory indicators as well as hepatic and renal function before and after treatment with tigecycline were compared.</p><p><b>RESULTS</b>Among 41 patients treated with tigecycline due to ineffectiveness of treatment with carbapenems, the infection had been controled in 34 cases, 7 patients died due to ineffectiveness of anti-infective treatment, these patients all were patients with relapse/refractory leukemia. 41 patients were examined etialogically, as a result, 22 patients showed possitive, among them the gram-negative bacill was found in 11(11/22) cases. The average deferves counce time of tigecycline was 28.2±12.0 hours. The temperature of patients treated with tigecycline for 48 hours decreased significantly (P<0.05). There were no significant differences in calcitonin and C-reactive protein levels after treatment with tigecycline (P>0.05), but cacitonin level displayed decrease tread. There was no hepatic and renal impairment after treatment with tigecycline, but levels of as partate aminotransferase, total bilirubin and blood area nitrogen in blood significantly increased as compared with levels before treatment with tigecycline (P<0.05).</p><p><b>CONCLUSION</b>The application of high dose tigecycline for treatment of febrile neutropenia is safety and effective. The high dose tigecycline can decrease the temperature, calcitonin and C-reactive protein levels, and can control infection without the hepatic and renal impairment, but it needs to be confimed by more prospective studies.</p>
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Humans , Anti-Bacterial Agents , Carbapenems , Febrile Neutropenia , Minocycline , Retrospective Studies , TigecyclineABSTRACT
Whether and how garlic-derived -allylmercaptocysteine (SAMC) inhibits hepatocellular carcinoma (HCC) is largely unknown. In the current study, the role of low-density lipoprotein receptor (LDLR)-related protein 6 (LRP6) in HCC progression and the anti-HCC mechanism of SAMC was examined in clinical sample, cell model and xenograft/orthotopic mouse models. We demonstrated that SAMC inhibited cell proliferation and tumorigenesis, while induced apoptosis of human HCC cells without influencing normal hepatocytes. SAMC directly interacted with Wnt-pathway co-receptor LRP6 on the cell membrane. LRP6 was frequently over-expressed in the tumor tissue of human HCC patients (66.7% of 48 patients) and its over-expression only correlated with the over-expression of -catenin, but not with age, gender, tumor size, stage and metastasis. Deficiency or over-expression of LRP6 in hepatoma cells could partly mimic or counteract the anti-tumor properties of SAMC, respectively. administration of SAMC significantly suppressed the growth of Huh-7 xenograft/orthotopic HCC tumor without causing undesirable side effects. In addition, stable down-regulation of LRP6 in Huh-7 facilitated the anti-HCC effects of SAMC. In conclusion, LRP6 can be a potential therapeutic target of HCC. SAMC is a promising specific anti-tumor agent for treating HCC subtypes with Wnt activation at the hepatoma cell surface.
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Fourier transform infrared spectroscopic imaging (FTIRSI) technology can simultaneously obtain microstructure information and infrared spectral information of the samples. The method of FTIRSI combined with chemometric algorithms can be used for quantitative analysis of sample spectral information and tissue discrimination research. Based on this, FTIRSI and support vector machine classification (SVC) for the first time were used in this work to discriminate healthy and degenerated articular cartilage, with high accuracies of 100％ and 95. 4％ , respectively, and sum accuracy of 97. 7％ . The support vector regression (SVR) model was used to quantitatively study the contents and distribution of two biomacromolecules, collagen and proteoglycan, in articular cartilage. The proteoglycan loss occurred in the degenerated articular cartilage, especially in the superficial area. This study indicates that the combination of FTIRSI and support vector machine (SVM) is expected to become a new diagnostic tool for osteoarthritis, which is of great significance for the early diagnosis and research of osteoarthritis.
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Objective To investigate whether the metabolite of benzene, 1, 4-benzoquinone (1, 4-BQ) , can activate PINK1/Parkin-mediated mitocphagy and the role of reactive oxygen species (ROS) in 1, 4-BQ induced mitophagy in vitro. Methods Human promyelocytic leukemia cells HL60 were used as the test cells, and were divided into control group, 1, 4-BQ group (10 μM 1, 4-BQ treated cells for 24 h), NAC group (5 mM antioxidant N-acetyl cysteine treated cells for 24 h) and 1, 4-BQ+NAC group (5 mM NAC preincubated for 1 h prior to the treatment with 10 μM 1, 4-BQ for 24 h) . The ultra structure of the cells were observed by transmission electron microscopy (TEM), and the expression of mitophagy related protein LC3, PINK1 and Parkin were detected by Western blot, and the intracellular ROS content was determined by DCFH-DA staining. Results The mitochondria in the control group showed a normal rod-shaped structure with clear mitochondrial cristae, while in the 1, 4-BQ group, the mitochondria showed a swollen structure with less mitochondrial cristae, and typical double-membrane mitophagosomes were observed. LC3-Ⅱ/LC3-Ⅰ ratio, the expression of PINK1, Parkin protein and ROS content in 1, 4-BQ group were increased compared with the control group (P <0.05) , and this increase was markedly blocked by the co-treatment of 1, 4-BQ and NAC (P <0.05) . Conclusion The 1, 4-BQ can induce PINK1/Parkin-mediated mitophagy and ROS plays a significant role in 1, 4-BQ-induced mitophagy.
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Objective To investigate if anesthetic sensitivity to propofol will be restored after biliary decompression.Methods Twenty-four adult male SD rats were randomly assigned into 3 groups:sham group (group S),irreversible obstructive jaundice group (group Ⅰ) and reversible obstructive jaundice group (group R).The serum total bilirubin (TBL) and total bile acid (TBA) concentratins were detected in the rat blood samples collected from the caudal vein before and after the operation,3,7,14,21 d respectively.Propofol was administered to measure the time of loss of righting reflex and recovery pre or 7th and 21th day post ligation.Results Serum TBL and TBA in group Ⅰ and serum TBA in group R were significantly higher than that in group S on 3rd,7th,14th,21th day post surgery(P＜0.05).Compared with group S,seum TBL in group R were significantly high on 3rd,7th,14th day post-surgery.Serm TBL and TBA in group R were significantly lower than group Ⅰ on 14th,21th day post-surgery (P＜0.05).Compared with group S,the time to loss of righting reflex in group I and group R were significantly shortened and the time to recovery were significantly increased on 7th day post-surgery (P＜0.05).Conclusion Obstructive jaundice could significantly potentiate the ability of propofol to induce a loss of righting reflex,and the increased anesthesia sensitivity will be restored after biliary decompression.
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Objective To evaluate the influence of dosage,operation method,adverse reaction of endoscopic photodynamic therapy (EPDT) on its therapeutic efficacy in rabbit models of in-situ rectal cancer,so as to provide preclinical basis of photodynamic therapy for rectal cancer.Methods 20 rabbits with in-situ VX2 rectal cancer were randomly divided into control group,PDT low dose group,intermediate dose group,and high dose group.At 24 h before PDT,photosensitizer (hermimether) was intravenously injected into rabbits.630 nm semiconductor laser was used as light source.The growth of the tumor was observed by conventional endoscopy and endoscopic ultrasonography,and the survival time,general conditions and adverse reactions were recorded.The histopathological changes were observed by hematoxylin-eosin staining.Results At 7 d after PDT,the total response rates of low dose,intermediate dose and high dose group respectively were 40％ (slight),80％ (60％ remarkable and 20％ slight),100％ (20％ remarkable and 80％ slight).The average survival times of the three groups were 14 d,10 d and 5 d,respectively.The main adverse reactions were inflammation,intestinal obstruction,intestinal peristalsis loss and death.Conclusions The dosage of PDT is an important factor to influence the curative effect.The appropriate dose of PDT will have a better effect on the treatment of rectal cancer.A thorough study of these problems is helpful to the clinical application of PDT in the treatment of rectal cancer.
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Objective:To better understand the pathogenesis of obstructive jaundice (O J),a variety of rat OJ and biliary drainage models have been tried;however,complications are still common.We aimed to establish a stable rat model of OJ using microsurgical techniques,and to assess its reversal by internal bile drainage(IBD).Methods:After the pilot study,we developed a standardized surgical procedure.All operations were carried out under an operating microscope.In the first laparotomy,the proximal common bile duct (CBD) of the rat was ligated and transected.A tube was introduced into the distal end of the duct,and the other end of the tube was sealed and fixed.In the second laparotomy,the drainage tube was inserted into the (by now markedly dilated) proximal CBD,and ligated into position.We evaluated the general condition of the rats,the status of the liver and pancreas before and after IBD.Results:Complications such as intestinal reflux and bile duct blockage,were not found.Pancreatic injury was not evident by day 4 after the first laparotomy.After biliary drainage,the serum glucose and albumin concentration rapidly returned to normal levels.Liver weight/body weight ratio increased.The biochemical indicators and ultrasonographic elastography results for the liver gradually returned to normal.Conclusion:Using microsurgical techniques,we have developed a stable rat model of OJ reversed by IBD.
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<p><b>OBJECTIVE</b>To investigate the clinical manifestation, features of laboratorial examination results and prognosis of patients with Ph/BCR-ABLacute myelogenous leukemia(AML).</p><p><b>METHODS</b>The clinical data of 5 AML patients with Ph/BCR-ABLadmitted in Department of Hematology of Chinese PLA general hospital from July 2007 to May 2015 were collected and their clinical characteristics, laboatorial examination results and long-term survival were analyzed.</p><p><b>RESULTS</b>The median age of 5 cases was 39 years old, and 2 cases with splenomegaly. All the cases were assayed for BCR-ABL fusion gene, and 2 of them were accompanied with other molecular abnormalities. In 4 cases, Ph chromosome was not found in one case, and one was with complex karyotype. 3 cases still are live till now and are treated by traditional chemotherapy combined with TKI, and consolidated by allo-HSCT. One case treated by traditional chemotherapy survived for 6 months. And one case treated by traditional chemotherapy combined with TKI survives till to now.</p><p><b>CONCLUSION</b>The survival time of Ph/BCR-ABLacute myelogenous leukemia is improved by the traditional chemotherapy combined with TKI and the consolidation with allo-HSCT.</p>