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Proteolysis targeting chimeras (PROTACs) is an innovative technique in targeted protein degradation. PROTACs is a heterobifunctional molecule which can bind to the E3 ligase and target protein to form a ubiquitination complex, resulting in the ubiquitin-proteasome system dependent degradation of target protein. PROTACs has been regarded as the promising method in drug discovery campaign, for its high commonality, potent degradation activity and unique selectivity profile. However, the catalytic mechanism also induces the uncontrollable protein degradation risk. Controllable PROTACs contain the responsive element in the molecular entity. In certain conditions, the element can be triggered to activate or terminate the degradation event. In this review, we will briefly summarize the strategies in controllable PROTACs and describe the representative examples according to the responsive mechanism. We hope this review could provide some insight into the further development of controllable PROTACs.
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Nrf2 is a multi-effect transcription factor, which plays a crucial role in cytoprotective system. With the deepening of research on new regulatory modes and biologic functions of Nrf2, the oncogenic role of Nrf2 in malignant transformed tumors is increasingly obvious. More and more evidences show that Nrf2 is involved in the whole process of tumor occurrence, development, metastasis and prognosis, and inhibiting Nrf2 may be a promising strategy in tumor therapy. However, the development of Nrf2 inhibitors is still in early stage. In this paper, the biological function of Nrf2 and its dual role in tumor are briefly introduced, and representative Nrf2 inhibitors are reviewed according to their structure types, so as to provide reference and ideas for the development of anti-tumor drugs centering on the regulation of Nrf2.
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Objective: In this study, black tea and Citrus maxima (BT-CM), yellow tea and C. maxima (YT-CM), green tea and C. maxima (GT-CM) as subjects, the active ingredient content and antioxidant activity of three tea and C. maxima (T-CM) were analyzed. The effects of three T-CMs on apoptosis of liver cells in vitro and its mechanism were further explored. Methods: National standard method and HPLC were used for active ingredient analysis. MTT, cell flow cytometry and Western blot were used to analyze the effects of three T-CMs on cell proliferation, apoptosis, and its underlying molecular mechanism. Results: The content of tea polyphenols, free amino acids, ratio of polyphenols and amino acids, ester catechins, non-ester catechins and caffeine in YT-CM and GT-CM was significantly higher than that of BT-CM. The in vitro antioxidant capacity of YT-CM and GT-CM was also significantly stronger than that of BT-CM. Three T-CMs had the effects of inhibiting proliferation, arresting cell cycle and inducing apoptosis in HepG2 and Bel7402 cells, especially YT-CM and GT-CM. Western blot analysis showed three T-CMs activated PI3K/AKT/mTOR signaling pathway and regulated the expression levels of apoptosis-related proteins Bax, Bcl-2 and Caspase-3/9. YT-CM and GT-CM had better ability to change the signal pathway than BT-CM. Conclusion: In short, T-CMs, which combined different degrees of fermentation tea with C. maxima, were rich in nutrients and biologically active substances. T-CMs, especially YT-CM and GT-CM, are healthy drinks that help to prevent and treat liver cancer.
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Reactive oxygen species (ROS) which were partial metabolites of oxygen are highly reactive. Different concentrations of ROS have different effects on tumor development. Tumor cells have a high level of reactive oxygen species. The antioxidant system of tumor is in highly activated state, and thus modulation of reactive oxygen species levels could be an effective strategy to target cancer cells. Treatment with small molecules that disrupt the redox balance can kill tumor cells first. This paper outlines the main ideas of developing anti-tumor drugs based on reactive oxygen species regulation, and summarizes the representative drugs and research progress according to the mechanism of action, in an effort to suggest potential reference and ideas for developing anti-tumor drugs based on reactive oxygen species regulation.
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OBJECTIVE@#Quantitative assessment of white blood flow in semi-oval center of patients with delayed neuropathological sequelae (DNS) after carbon monoxide poisoning treated with acupuncture combined with hyperbaric oxygen (HBO) based on magnetic resonance multi-inversion time arterial spin labeling imaging (mTI-ASL), and to evaluate its efficacy indirectly.@*METHODS@#Twenty-six patients with clinically diagnosed DNS were randomly divided into an observation group (13 cases) and a control group (13 cases). The conventional therapy combined with HBO were given in the control group. In the observation group,on the base of the treatment, acupuncture was applied, the main acupoints were Shuigou (GV 26), Neiguan (PC 6), Baihui (GV 20), Shangxing (GV 23), Yintang (GV 29), Sanyinjiao (SP 6) on the affected side, Sishencong (EX-HN 1), Fenglong (ST 40), Lianquan (CV 23) and Jinjin (EX-HN12) for slurred speech, Jianyu (LI 15), Waiguan (TE 5) and Shousanli (LI 10) for upper limb pain, Huantiao (GB 30), Yanglingquan (GB 34), Yinlingquan (SP 9) for lower limb pain, the treatment was given once every day, 5 days as one course, with an interval of 2 days between the course. The treatment for 6 courses was required. The conventional head MR scan, mTI-ASL and diffusion tensor imaging (DTI) scans before and 1 week after treatment were adopted, Matlab (R2014b), Mricron and Syngo.via software were adopted to measure the cerebral blood flow (CBF) and anisotropy (FA) values of the semi-oval center. The correlation between the parameters was evaluated by Pearson method. And the simple intelligent mental state examination scale (MMSE) was uesd to assess cognitive function.@*RESULTS@#After treatment, the CBF, MMSE scores in both groups and FA values in the observation group were higher than those before treatment (<0.05). After treatment, the CBF, FA and MMSE scores in the observation group were significantly higher than those in the control group (<0.05). There was a positive correlation between CBF, FA and MMSE scores (<0.05), and the correlation between CBF and MMSE was the best ( =0.822).@*CONCLUSION@#Acupuncture combined with hyperbaric oxygen can significantly improved early white matter hypoperfusion and improved cognitive function score in patients with DNS. The curative effect is better than that of hyperbaric oxygen therapy alone. The mTI-ASL imaging can quantitatively evaluate its curative effect.
Subject(s)
Humans , Acupuncture Therapy , Carbon Monoxide Poisoning , Diffusion Tensor Imaging , Hyperbaric OxygenationABSTRACT
Objective To optimize the extraction conditions of Schisandra sphenanthera(SS)seed oil by supercritical CO2ex?traction and identify its components by GC-MS.Methods SS seed oil was used as tested material,response surface methodology was used to optimize the process of supercritical CO2extraction,and GS-MS method was used to analyse SS seed oil composition.Results A model of an equation was established,which could be used to optimize the process parameters of supercritical CO2extraction of SS seed oil. The optimum extraction parameters were as follows:the extraction pressure was 33 MPa,the extraction temperature was 53℃,the extraction time was 90 min,the CO2flow rate was 21.40 ml/min.In this condition,the extraction rate of SS seed oil was 7.97%.The SS seed oil was analyzed by GC-MS,and 23 compounds were identified.In these compounds,(1α,4a.β,8a.α)-1,2,3, 4,4a,5,6,8a-octahydro-7-methyl-4-methylene-1-(1-methylethenyl)-naphthalene,(-)-1,7-dimethyl-7-(4-methyl-3-pentenyl)-tricyc?lo[2.2.1.0(2,6)]heptane and(R)-2,4a,5,6,7,8-octahydro-3,5,5,9-tetramethyl-1H-(σ-phenyl)cycloheptene had the content of more than 10% and the contents were 27.78%,14.77% and 13.12% respectively.Conclusion This process has high extraction rate, fast speed and simple operation,and can be used for the extraction of SS seed oil.
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Objective To analyze the safety of atrial septal defect closure using Da Vinci surgical system. Methods Totally 23 atrial septal defect patients hospitalized from July to December 2016 underwent atrioseptopexy by using Da Vinci surgical system. The effect of atrioseptopexy was observed under cardiopulmonary bypass conditions. Results All the patients had the operation completed successfully, with the operating time being (2.8 ±0.5)h, the intraoperative cardiopulmonary bypass time being (35.4±18.4)min, aortic clamping time being (25.9±8.4)min, postoperative mechanical ventilation time being (5.7±1.5)h, amount of thoracic drainage fluid from 50 to 300 ml and postoperative hospital stay being (7 ±5.1)d. The follow-up 1 and 3 months after discharge showed there were no complications and death occurred, and the examinations by chest X-ray film and heart color ultrasound found no abnormality. Conclusion Da Vinci surgical system gains advantages in safety, reliability, patient satisfaction, operative incision and surgical trauma, and thus is worthy promoting clinically.
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ObjectiveTo explore the effects of eukaryotic translation initiation factor 6 (eIF6) on the expression of fibrotic cy tokines and metabolic enzymes derived from M2 macrophages. MethodseIF6 wild type mice (eIF6+/+) and eIF6 knock out mice (eIF6+/-) were used. Macrophages were collected from peritoneal lavage fluid, and they were stimulated with IL-4 for enrichment of M2 macrophages. The differential gene expressions of eIF6+/+ and eIF6+/- M2 macrophages were studied with gene chip. The differential expression of genes was further confirmed with both RT-PCR and ELISA. ResultsThe gene chip showed that the expressions of VEGF and TIMP-2 were down-regulated in eIF6+/+ macrophages compared with those in eIF6+/- M2 macrophages, while the expression of MMP-2 was up-regulated in eIF6+/+ M2 macrophages (P<0.05). The result of RT-PCR and ELISA had confirmed that the RNA and protein expressions of VEGF and TIMP-2 were decreased in eIF6+/+ macrophages compared with those in eIF6+/- M2 macrophages, while the RNA and protein expressions of MMP-2 were up-regulated in eIF6+/+ M2 macrophages (P<0.05). ConclusioneIF6 not only inhibits the expression of VEGF, reduces angiogenesis and granulation tissue formation, but also enhances the extracellular matrix degradation and deposition by regulating the balance of MMP2/TIMP2, and thus attenuating the degree of fibrosis (scar formation).
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<p><b>OBJECTIVE</b>Current study was conducted to investigate and compare the impact of temperature and pH on the activities of amylase, protease and lipase in alimentary tract of Whitmania pigra.</p><p><b>METHOD</b>The responses of amylase, protease, and lipase activities were determined over a wide range of temperatures (7-52 degrees C) and pH gradient (2.2-11.2).</p><p><b>RESULT</b>The highest lipase activity was found under 37 degrees C, pH 8.2, and the highest amylase activity was detected under 37 degrees C, pH 5.2, while protease activity peaked at 42 degrees C, pH 3.2 or pH 9.2.</p><p><b>CONCLUSION</b>The optimal temperature in alimentary tract of Wh. pigra for lipase and amylase was 37 degrees C, and the responding temperature for protease was 42 degrees C. The optimal pH value in alimentary tract of Wh. pigra for lipase and amylase was pH 8.2 and pH 5.2, respectively. While pH 3.2 or 9.2 seems to be both favorable for high protease activity.</p>