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Targeted therapeutic drugs for acute myeloid leukemia (AML) are showing immense development, thereby laying a solid foundation for the precise treatment of AML patients. The paper reviews four types of targeted drugs that have progressed rapidly for AML treatment (by targeting genes or signaling-pathway alterations, targeting apoptosis-related pathways, targeting cell-surface antigens, and targeting immune-related substances). We look forward to the future development directions of targeted drugs, providing references for hematologists and developers of new drugs for AML.
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Tetraacetyl phytosphingosine (TAPS) is an excellent raw material for natural skin care products. Its deacetylation leads to the production of phytosphingosine, which can be further used for synthesizing the moisturizing skin care product ceramide. For this reason, TAPS is widely used in the skin care oriented cosmetics industry. The unconventional yeast Wickerhamomyces ciferrii is the only known microorganism that can naturally secrete TAPS, and it has become the host for the industrial production of TAPS. This review firstly introduces the discovery, functions of TAPS, and the metabolic pathway for TAPS biosynthesis is further introduced. Subsequently, the strategies for increasing the TAPS yield of W. ciferrii, including haploid screening, mutagenesis breeding and metabolic engineering, are summarized. In addition, the prospects of TAPS biomanufacturing by W. ciferrii are discussed in light of the current progresses, challenges, and trends in this field. Finally, guidelines for engineering W. ciferrii cell factory using synthetic biology tools for TAPS production are also presented.
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Sphingosine , Ceramides , Metabolic Engineering , Synthetic BiologyABSTRACT
Objective To establish a druggability evaluation method for new targets of anti-tumor drugs by analyzing the mutation genes of common tumors in the digestive system. Methods We collected the mutant gene data of the five common tumors of the digestive system (esophageal cancer, gastric cancer, colorectal cancer, liver cancer and pancreatic cancer) in the Integrative Onco Genomics database, and screened out the genes with higher mutation rates in each tumor. We evaluated the druggability of these genes or their encoded proteins, and discovered the potential targets for the new anti-tumor drugs. Results A total of five tumors, 35 cohorts and 5445 tumor samples were collected in this study. The top 10 mutation genes were selected for further analysis. The canSAR database was used to analyze the druggability of unpublished mutant genes or their encoded proteins, and a total of 17 potential therapeutic drug targets were screened out. Conclusion A method for evaluating druggability of targets based on mutant genes or their encoded protein is established in this study. The application of this method can provide a reference for discovering new anti-tumor therapeutic target, saving the cost and time of target screening in new drug development.
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Objective To evaluate different inflammation markers for predicting the risk of acute kidney injury (AKI) in sepsis patients. Methods A retrospective observational study was conducted. The adult patients with sepsis for more than 24 hours admitted to intensive care unit (ICU) of Beijing Friendship Hospital, Capital Medical University from March 1st, 2010 to November 1st, 2017 were enrolled. Inflammatory markers such as white blood cell count (WBC), erythrocyte sedimentation rata (ESR), neutrophil and lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin (PCT), etc. were collected at ICU admission. The patients were divided into different groups according to the 24-hour AKI, and subgroup analysis was conducted according to the criteria of the Global Renal Disease Prognostic Organization (KDIGO)-AKI staging. The receiver operating characteristic curve (ROC) was plotted with statistically significant inflammatory markers to assess the predictive value of AKI for patients with systemic infection. Results A total of 753 patients with sepsis were enrolled. 405 AKI patients were diagnosed within 24 hours, with a prevalence of 53.8%. There were 118 cases (15.7%) in AKI stage 1, 48 cases (6.4%) in stage 2 and 239 cases (31.7%) in stage 3. PCT in AKI group was significantly higher than that in non-AKI group [μg/L: 4.98 (1.51, 32.75) vs. 3.00 (0.37, 11.40), P < 0.01]. PCT of AKI stage 2 group was significantly higher than that of AKI stage 1 and 3 groups [μg/L: 27.86 (4.80, 37.26) vs. 3.00 (0.98, 16.10), 4.98 (1.51, 42.55), both P < 0.01]. Although ESR in AKI group was lower than that of non-AKI group (mm/1 h: 45.25±37.42 vs. 52.28±34.89, P < 0.01), there was no significant difference among the subgroups. CRP in AKI group was slightly higher than the non-AKI group [mg/L: 96.00 (42.20, 160.00) vs. 73.60 (21.01, 157.50)], but the difference was not statistically significant (P > 0.05). There was no significant difference in WBC or NLR between AKI group and non-AKI group. It was shown by ROC curve analysis that the area under ROC curve (AUC) of PCT in predicting the occurrence of septic AKI was 0.619, with the 95% confidence interval (95%CI) of 0.545-0.689 (P < 0.01). When the cut-off value of PCT > 0.4 μg/L, the sensitivity was 94.2%, the specificity was 26.5%, the accuracy was 64.2%, the positive predictive value was 61.6%, and the negative predictive value was 78.6%. Conclusion PCT could be a marker to predict AKI with sepsis patients.
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Objective To investigate the analysis of collateral circulation in patients with acute symptomatic internal carotid artery occlusion (ICAO)and its clinical significance. Methods Seventy-two consecutive patients with symptomatic ICAO diagnosed by digital subtraction angiography (DSA)were enrolled retrospectively. The American Society of Intervention and Treatment Neuroradiology / Society of Interventional Radiology (ASITN/ SIR)scores were used to evaluate the collateral circulation in the region of ICAO,and the collateral circulation of the patients with different causes,different clinical manifestations, and different types of infarcts were compared. Results Of the 72 patients with ICAO,61(84. 7%)had atherosclerotic occlusion,8(11. 1%)had cervical dissection,and 3 (4. 2%)had cardioembolism;55 patients (76. 4%)had cerebral infarction and 17(23. 6%)had transient ischemic attack. There were no significant differences in the ASITN/ SIR scores among the different causes (P > 0. 05). The ASITN/ SIR scores in patients with cerebral infarction and transient ischemic attack were 2. 64 ± 0. 80 and 3. 29 ± 0. 69 respectively. There was significant difference (P < 0. 05). In patients with cerebral infarction,the ASITN/SIR scores in patients with internal watershed infarction and regional cerebral infarction only were 2. 43 ± 0. 68 and 2. 36 ±0. 51 respectively,they were lower than the patients with only external watershed infarction only and/ or cerebral infarction in cortical territory (3. 42 ±0. 90,P <0. 05). Conclusion Atherosclerotic occlusion is the most common cause of ICAO. ASITN / SIR scores may reflect the conditions of collateral circulation in patients with ICAO. The occurrence of internal watershed infarction and regional infarction indicates the collateral circulation is poor,and need for further therapeutic intervention.
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We studied the effects of three inorganic carbon sources, Na2CO3, NaHCO3 and CO2, and their initial concentrations on lipid production of Chlorella vulgaris. Chlorella vulgaris could utilize Na2CO3, NaHCO3 and CO2 to produce lipids. After 10-day cultivation with each of the three inorganic carbon sources, lipid yield of Chlorella vulgaris reached its peak with the concentration increase of the inorganic carbon source, but dropped again by further increase of the concentration. The pH value of the culture medium for Chlorella vulgaris increased after the cultivation on inorganic carbon source. The optimal concentration of both Na2CO3 and NaHCO3 was 40 mmol/L, and their corresponding biomass dry weight was 0.52 g/L and 0.67 g/L with their corresponding lipid yield 0.19 g/L and 0.22 g/L. When the concentration of CO2 was 6%, Chlorella vulgaris grew the fastest and its biomass dry weight was 2.42 g/L with the highest lipid yield of 0.72 g/L. When the concentration of CO2 was too low, the supply of inorganic carbon was insufficient and lipid yield was low. A too high concentration of CO2 caused a low pH and lipid accumulation was inhibited. Na2CO3 and NaHCO3 were more favorable for Chlorella vulgaris to accumulate unsaturated fatty acids than that of CO2.
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Biofuels , Carbon , Metabolism , Carbon Dioxide , Pharmacology , Carbonates , Pharmacology , Chlorella vulgaris , Metabolism , Culture Media , Culture Techniques , Methods , Lipids , Sodium Bicarbonate , PharmacologyABSTRACT
Docosahexenoic acid (DHA) is an important polyunsaturated fatty acid which is beneficial to human health. Compared with the DHA derived from fish oil, DHA by microbial production possesses many advantages, and has a bright prospect. In this article, we reviewed strains, metabolic pathway, key enzymes and mechanism of lipid accumulation for microbial production of DHA. Those information would be greatly helpful for further improving DHA production by metabolic engineering.
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Docosahexaenoic Acids , Eukaryota , Metabolism , Fermentation , Industrial Microbiology , Methods , Metabolic Engineering , MethodsABSTRACT
Arachidonic acid, as an important polyunsaturated fatty acid, is identified as potential food additives or pharmaceuticals for their biological activities. In recent years, arachidonic acid production by Mortierella alpina is becoming a research highlight. The prophase relevant researches focused on the mutagenic breeding and fermentation optimization. With the depth of investigation, the advancement concerning pathway for the biosynthesis of arachidonic acid in Mortierella alpina has been made. In this review, we summarized the prophase work briefly. Mainly, we discussed the biosynthesis pathway of arachidonic acid, the key enzymes, the construction of transformation system and the genetic modification. In addition, the prospect of microorganism arachidonic acid production is put forward.
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Arachidonic Acid , Culture Media , Culture Techniques , Methods , Genetic Engineering , Methods , Mortierella , Genetics , MetabolismABSTRACT
Objective To investigate the feasibility and safety of combined coronary and renal angiographies through transradial approch.Methods Three hundred and twenty patients in hospital from August 2007 to April 2009 who underwent combined coronary and renal angiographies through transradial approach were included in this study.Renal artery angiography of 300 cases was done by 5 FMP-A1 catheter (MP-A1 group),and 20 cases was done by TIG catheter (TIG group).Control group had 625 patients in hospital from January 2004 to April 2009 who underwent combined coronary and renal angiographies through transfemoral approach.The achievement ratio,operating time,dosage of contrast agent and complication of angiography were observed.Results The achievement ratio was higher in MP-A1 group [97.0%(291/300) ]and control group [98.4%(615/625)]than that in TIG group [40.0%(8/20)](P< 0.01).The operating time was (32.21 ± 3.37) min and the dosage of contrast agent was (52.72 ± 7.91) ml in MP-A1 group,and it was (30.78 ± 3.23) min and (51.88 ± 7.22) ml in control group respectively.There was no significant difference between two groups(P>0.05).The operating time was (26.42 ±4.31) min and the dosage of contrast agent was(51.72 ± 10.11) ml in TIG group.There was significant difference in the operating time between TIG group and the others groups (P < 0.05).The complications of angiography through transradial approach (0.9%,3/320) were less than those through transfemoral approach (3.0%,19/625) (P <0.05).Conclusions Renal artery angiography through transradial approach by 5 F MP-A1 catheter(125 centimeter) is safe and has minor complication.The achievement ratio of transradial approach for renal artery angiography by 5F MP-A1 catheter is higher than that by TIG catheter.
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Objective To investigate the clinical presentation,diagnosis,and surgical management of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis.Methods One case of anti-NMDA receptor encephalitis in a previously healthy 17-year-old female related to the development of NMDA receptor autoantibodies triggered by an ovarian teratoma was reported.The related literature was reviewed and the clinical feature was summarized.Results Removal of the ovarian teratoma combined with intravenous immuneglobulin and corticosteroid proved curative with eventual resolution of the paraneoplastic disease process and associated psychiatric symptoms.Conclusion Increasingly,reports of anti-NMDA receptor encephalitis associated with ovarian teratomas,as well as a novel assay to measure these antibodies suggest an etiology for this disease process that may be amenable to prompt surgical excision.
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@#Objective To observe the expression of IL-6 mRNA and study the mechanism of acupuncture in focal cerebral ischemia.Methods In situ hybridization was used to detect the expression of IL-6 mRNA in the sham operation group, control group and acupuncture group 2 h, 6 h, 12 h, 24 h after reperfusion in the brain of middle cerebral artery occlusion rats, meanwhile and also observe ultrastructure in cortex of ischemic brain tissue 24 h after reperfusion.Results The sham operation group showed a basic expression of IL-6 mRNA in cortex and striate body. The cells expressing IL-6 mRNA were increased 2 h after ischemic reperfusion in cortex and striate body and peaked 24 h after reperfusion in control group and acupuncture group. The cells expressing IL-6 mRNA in cortex of ischemic area were stronger in acupuncture group than in control group at every research time point besides 2 h after ischemic reperfusion. The cells expressing IL-6 mRNA striate body of ischemic area were stronger in acupuncture group than in control group at every research time point. Acupuncture can lighten the degeneration of cell nucleolus and necrosis of cell, resume the integrity of the nucleolus, improve the function of mitochondrial and endoplasmic, and have significant difference with control group. Conclusion Acupuncture can increase the cells expressing of IL-6 mRNA.
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Objective To observe the early rehabilitation effect of mild hypothermia on patients with herpes simplex viral encephalitis (HSE). Methods A total of 58 patients with HSE were randomized into two groups, a mild hypothermia therapy group (30 cases) and a normothermia control group (28 cases). Their rectal temperatures were controlled to (34±1)℃ and (37.0±0.5)℃ respectively. Serum levels of neuron specific enolase (NSE) were determined through radio-immunoassay (RIA). Soluble intercellular adhesion molecule-1 (sICAM-1) was measured with ELISA before and 1, 3, 5, and 7 d after treatment. The outcome was evaluated using the Glasgow Outcome Scale (GOS) 30 days after treatment. Results Compared with the normothermia control group, the mild hypothermia group's serum levels of NSE and sICAM-1 decreased quickly and significantly during the early stage of treatment and remained better 30 d later. Conclusion Mild hypothermia therapy can dramatically reduce inflamma-tion and facilitate the rehabilitation of damaged neurons, provide protective effects and improve the outcome for pa-tients with SHE.
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Objective To know the prevalence rate of hypertension and the rates of illness-awareness,medication and blood pressure control in Wenzhou. Method With random cluster sampling,1 034 residents aged≥15 yrs were selected from the communities of Wenzhou,and investigated with the standard questionnaires. Results The prevalence rate of hypertension in Wenzhou was 38.97% and the standardized rate was 22.27%. Among the patients with hypertension,51.12% of them were aware,and only 40.69% of them took medication and 9.18% of them had their blood pressure controlled. Conclusion The prevalent rate of hypertension is higher,but the awareness rate,medication rate and controlling rate are lower in Wenzhou city. The comprehensive interventions are needed for the prevention and treatment of hypertension.