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Dysregulation of histone deacetylases (HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors (HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.
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Objective:To observe the effect of early temperature control on the prognosis of brain injury patients after severe carbon monoxide poisoning (COP).Methods:A total of 277 patients hospitalized with severe COP were randomly divided into a fever group ( n=78), a normal temperature group ( n=113) and a mild hypothermia group ( n=86). All were given hyperbaric oxygen therapy and any necessary supportive treatment. The mild hypothermia group were kept in a room at 34 to 35℃. Evaluation was with the Glasgow Coma Scale (GCS), version II of the Acute Physiology and Chronic Health Evaluation (APACHE), the Hasegawa dementia scale (HDS) and the mini mental state examination (MMSE). The incidence of delayed encephalopathy (DEACMP) and mortality were compared among the three groups. The bispectral index (BIS) and neuron-specific enolase (NSE) levels were correlated with DEACMP. Results:After the treatments, improvement was observed in multiple indexes of all three groups compared with before the treatment. Compared with the fever group, the average GCS of the mild hypothermia group was significantly higher on the 2nd, 4th, 8th and 31st day after the intervention. It was significantly higher than the normal temperature group′s averages on the 4th, 8th and 31st day. The average APACHE scores of the normal temperature and the mild hypothermia groups were significantly lower than the fever group′s average, with that of the mild hypothermia group significantly lower than that of the normal group. The average HDS scores of the normal temperature and mild hypothermia groups were significantly higher than the fever group′s average, with that of the mild hypothermia group significantly higher than that of the normal group. The average MMSE score of the mild hypothermia group was significantly improved after 7 days, one month and three months of treatment. That of the normal group showed significant improvement after one and three months, but the mild hypothermia group′s averages were superior. Compared with the fever group, the average BIS score of the mild hypothermia group was significantly better after one, three and seven days, and one month. This was true for the normal group beyond three days after the intervention. The average NSE concentration of the normal group after 7 days and one month was significantly lower than that of the fever group. For the mild hypothermia group this was true after only 3 days. Compared with the other two groups, the average coma time, incidence of DEACMP and nervous system injury were significantly lower in the hypothermia group. The average GCS, BIS and NSE values were closely related to the occurrence of DEACMP.Conclusions:Early temperature control can significantly reduce the severity of brain injury after COP and reduce the incidence of neurological sequelae. Early dynamic detection of GCS, NSE concentration and BIS is of great significance for predicting the incidence of DEACMP.
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Heparinase II (Hep II) from Flavobacterium heparinum is an enzyme that could specifically cleave certain sequence of heparin and heparan sulfate. In this work, fermentation conditions of recombinant heparinase II (His-Hep II) producing bacteria were optimized, including initial induction time, inducer (IPTG) concentration, induction temperature and induction time. The optimum conditions were as follows: cultivating recombinant bacteria to exponential prophase under 37 degrees C, then adding IPTG to a final concentration of 0.3 g/L, finally cultivating recombinant bacteria under 20 degrees C for 10 h. The total crude enzyme activity reached 570 U/L. Based on these results, high cell density fermentation of recombinant bacteria was studied. The final OD600 could reach 98 and the total crude enzyme activity of His-Hep II increased to 9 436 U/L.
Subject(s)
Fermentation , Flavobacterium , Metabolism , Microbiological Techniques , Polysaccharide-Lyases , Recombinant ProteinsABSTRACT
BACKGROUND:With unique structure and physicochemical property, carbon nanotubes have promising application prospects in the fields of drug delivery, biosensor and biomaterials. However, carbon nanotubes are highly hydrophobic and trend to aggregate, and thus carbon nanotubes are hard to be dispersed in solution. Furthermore, carbon nanotubes induce blood coagulation and have cytotoxicity, which greatly limit the application of carbon nanotubes. OBJECTIVE:To prepare heparinized single-wal ed carbon nanotubes and to study the effects of heparin-immobilization on the water solubility, stability as wel as biocompatibility of carbon nanotubes. METHODS:By the method of covalent grafting, heparinized single-wal ed carbon nanotubes was fabricated and characterized by Fourier transform infrared spectroscopy and carbazole assay. Transmission electron microscopy was used to investigate the dispersing performance and suspension stability of heparinized single-wal ed carbon nanotubes in aqueous solution. Anti-Xa activity and activated partial thromboplastin time assays were used to measure the anticoagulation activity of heparinized single-wal ed carbon nanotubes. MTT assay was used to evaluate the cytocompatibility of heparinized single-wal ed carbon nanotubes. RESULTS AND CONCLUSION:Heparin was covalently linked to the surface of single-wal ed carbon nanotubes successful y. The amount of heparin on single-wal ed carbon nanotubes was measured to be 257.53 mg/g. Heparinized single-wal ed carbon nanotubes were wel dispersed and stable in an aqueous solution without aggregation. The anti-Xa activity of heparinized single-wal ed carbon nanotubes was measured to be 36.53 U/mg, suggesting a significant anticoagulant activity. Further study of activated partial thromboplastin time assay found that the anticoagulant effect of heparinized single-wal ed carbon nanotubes could be prolonged. MTT assay revealed that heparinized single-wal ed carbon nanotubes had no cytotoxicity and showed good cytocompatibility. Taken together, the immobilization of heparin on single-wal ed carbon nanotubes wil not only improve its solubility and stability in water, but also endow it with excellent biocompatibility.
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To establish a quantitative estimate model for diagnosing traditional Chinese medicine (TCM) syndromes of patients with osteoporosis.
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To establish diagnostic criteria for common traditional Chinese medicine (TCM) syndromes in osteoporosis.
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A novel method of feature extraction from protein primary structure has been proposed and applied to classify the protein homodimer, homotrimer, homotetramer and homohexamer, i. e. one protein sequence can be represented by a feature vector composed of amino acid compositions and a set of weighted auto-correlation function factors of amino acid residue index. As a result, high classification accuracies are obtained. For example, with the same support vector machine (SVM), the total accuracies of QIANA, AIANB, MEEJ, ROBB and SNEP sets based on this novel feature extraction method are 77.63, 77.16, 76.46, 76.70 and 75.06% respectively in Jackknife test, which are 6.39, 5.92, 5.22, 5.46 and 3.82 percent points respectively higher than that of COMP set based on the conventional method composed of amino acid compositions. With the same QIANA set, the total accuracy of SVM is 77.63%, which is 16.29 percent points higher than that of covariant discriminant algorithm. These results show: (1) The novel feature extraction method is effective and feasible, and the feature vectors based on this method may contain more protein quaternary structure information and appear to capture essential information about the composition and hydrophobicity of residues in the surface patches buried in the interfaces of associated subunits; (2) SVM can be referred as a powerful computational tool for classifying the homo-oligomers of proteins.