[Drug Discrimination Method Based on Near Infrared Reflectance Spectrum and Balance Cascading Sparse Representation Based Classification].

The combination of near infrared spectrum and pattern recognition methods has a wide application prospect in rapid and nondestructive supervision and management of drugs. The traditional identification methods regard the smallest error rate as the goal while the imbalance of classes is ignored. This makes the positive class is overwhelming covered by the negative class and reduces its effect for the classifier, so that the classification results tend to recognize the negative class correctly, which severely affects the identification accuracy. In this paper, we mainly studied the class imbalance problems of true or false drugs via infrared spectral data of its, and then propose a balance cascading and sparse representation based classification method (BC-SRC) by combining the Balance Cascading with SRC. We sampling majority samples from the majority class for several times, which has the same size as minority samples and the majority samples we sampled can contain all the majority class samples entirely (sampling times is ceiling the result of majority samples number divide minority samples number). We can get sets of results, and then obtain the final predict labels form those results. Experiments of three databases achieved on Matlab2012a shows that the method is effective. From the experimental results, it can be seen that the method is superior to the commonly used Partial Least Squares (PLS), Extreme Learning Machine (ELM) and BP. Particularly, for the imbalanced databases, when the imbalance factor is greater than 10, the proposed method has more stable performance with higher classification accuracy than the existing ones mentioned above.

[Sparse Denoising Autoencoder Application in Identification of Counterfeit Pharmaceutical].

Near-infrared(NIR)As a fast and non-destructive testing technology, spectroscopy techniques is very suitable for pharmaceutical discrimination. Autoencoder network, as a hot research topic, has drawn widespread attention in machine learning research in recent years. Compared with traditional surface learning algorithm models, Autoencoder network has more powerful modeling capability as a typical deep networks model. Based on the unsupervised greedy layer-wise pre-training, autoencoder trains the network layer by layer while minimizing the error in reconstructing. Each layer is pre-trained with an unsupervised learning algorithm, learning a nonlinear transformation of the input of each layer which is the output of the previous layer. Pre-whitening process could get the inner structural features of the data more effectively. The supervised fine-tuning is followed with the unsupervised pre-training which sets the stage for a final training phase. The deep architecture is fine-tuned with respect to a supervised training criterion with gradient-based optimization. In this paper, firstly, the preprocessing step and pre-whitening transformation were used to treat near-infrared spectroscopy data of erythromycin ethylsuccinate, The pre-whitening transformation would reduce the correlation of the features, which gave each feature the same variance. Experimental results showed that the pre-whitening process had improved the classification accuracy of Sparse Denoising Autoencoder (SDAE) effectively. The SDAE with two hidden layers combined with pre-whitening was used to build the classification model for the identification of counterfeit pharmaceutical. The BP neural networks was compared with SVM algorithm for the classification accuracy and mean absolute difference (MAD). SDAE algorithm had higher classification accuracy than BP neural networks which had the same network structure with the SDAE networks, and SDAE algorithm also performed better than the SVM algorithm when the train datasets achieved a certain amount. As to the generalization performances, SDAE algorithm had less mean absolute difference of classification accuracy than SVM and BP Neural Networks. This result showed that SDAE algorithm could be effectively used to discriminate the counterfeit pharmaceutical.

Honokiol induces cell cycle arrest and apoptosis via inhibiting class I histone deacetylases in acute myeloid leukemia.

Honokiol, a constituent of Magnolia officinalis, has been reported to possess potent anti-cancer activity through targeting multiple signaling pathways in numerous malignancies including acute myeloid leukemia (AML). However, the underlying mechanisms remain to be defined. Here, we report that honokiol effectively decreased enzyme activity of histone deacetylases (HDACs) and reduced the protein expression of class I HDACs in leukemic cells. Moreover, treatment with proteasome inhibitor MG132 prevented honokiol-induced degradation of class I HDACs. Importantly, honokiol increased the levels of p21/waf1 and Bax via triggering acetylation of histone in the regions of p21/waf1 and Bax promoter. Honokiol induced apoptosis, decreased activity of HDACs, and significantly inhibited the clonogenic activity of hematopoietic progenitors in bone marrow mononuclear cells from patients with AML. However, honokiol did not decrease the activity of HDACs and induce apoptosis in normal hematopoietic progenitors from unbilicial cord blood. Finally, honokiol dramatically reduced tumorigenicity in a xenograft leukemia model. Collectively, our findings demonstrate that honokiol has anti-leukemia activity through inhibiting HDACs. Thus, being a relative non-toxic agent, honokiol may serve as a novel natural agent for cancer prevention and therapy in leukemia.

Anticancer effects of baicalein on hepatocellular carcinoma cells.

The therapeutic potential of baicalein against hepatoma cells was evaluated in vitro and in vivo. In cell viability assays, baicalein showed significant cytotoxicity against the hepatocellular carcinoma cell lines H22, Bel-7404, and Hep G2 and moderate cytotoxicity against immortalized human hepatocytes. Baicalein induced G0/G1-phase arrest in hepatocellular carcinoma cells, inhibited AKT, and promoted the degradation of ß-catenin and cyclin D1 without activation of GSK-3ß. Furthermore, baicalein significantly inhibited H22 xenograft tumor growth without causing obvious adverse effects on weight or liver and spleen weight indexes in ICR mice. Immunohistochemical analysis showed that the inhibition of tumor growth in baicalein-treated mice was associated with decreased AKT, ß-catenin, and cyclin D1 expression ex vivo. Our data indicate that baicalein might regulate cyclin D1 transcription via a ß-catenin-dependent mechanism, leading to cell cycle arrest at G0/G1 phase and impaired cancer cell proliferation. These results suggest that baicalein is a potential candidate for the treatment of hepatocellular carcinoma.

[Subtype classification of ceftriaxone sodium and its influence on the quality of product].

Powder X-ray diffraction (PXRD) technology combined with cluster analysis method was used to classify 75 batches of crystalline ceftriaxone sodium into subtypes, the crystalline characteristics of each subtype were measured with scanning electron microscope (SEM). By comparing some parameters of these subtypes correlated to crystallization process of ceftriaxone sodium, such as salification rate, water content in different subtypes, as well as by studying different lattice stabilities, different compatibilities with rubber closures during accelerated stability tests, the key point to improve the quality of domestic ceftriaxone sodium was disclosed. The results of this paper indicated that the fine structure of the products could be controlled well by improving the salification and crystallization process. As a result, the subtype II of ceftriaxone sodium with high stability can be produced.

[Rapid determination of hypoglycemic tablets by handheld Raman spectrometer and KPCA-clustering analysis].

In the present paper, five different kinds of hypoglycemic tablets were identified using kernel principal component analysis (KPCA)-clustering analysis of their Raman spectra. KPCA was used to compress thousands of spectral data into several variables and to describe the body of the spectra before clustering analysis was chosen as further research method. The results showed that hypoglycemic tablets could be quickly classified using KPCA-clustering analysis. A disadvantage of Raman spectroscopy for this type of analysis is that it is primarily a surface technique. As a consequence, the spectra of the tablet core and its coating might differ. However, the KPCA-clustering analysis turned out to be a sufficiently reliable discrimination, i. e., 96% of the hypoglycemic tablets with coating and 100% of the hypoglycemic tablets without coating were predicted correctly. Overall, the Raman spectroscopic method in the present paper plays a good role in the identification and offers a new approach to the rapid discrimination of different kinds of hypoglycemic tablets.

Ribosome-inactivating proteins isolated from dietary bitter melon induce apoptosis and inhibit histone deacetylase-1 selectively in premalignant and malignant prostate cancer cells.

Epidemiologic evidence suggests that a diet rich in fruits and vegetables is associated with a reduced risk of prostate cancer (PCa) development. Although several dietary compounds have been tested in preclinical PCa prevention models, no agents have been identified that either prevent the progression of premalignant lesions or treat advanced disease. Momordica charantia, known as bitter melon in English, is a plant that grows in tropical areas worldwide and is both eaten as a vegetable and used for medicinal purposes. We have isolated a protein, designated as MCP30, from bitter melon seeds. The purified fraction was verified by SDS-PAGE and mass spectrometry to contain only 2 highly related single chain Type I ribosome-inactivating proteins (RIPs), alpha-momorcharin and beta-momorcharin. MCP30 induces apoptosis in PIN and PCa cell lines in vitro and suppresses PC-3 growth in vivo with no effect on normal prostate cells. Mechanistically, MCP30 inhibits histone deacetylase-1 (HDAC-1) activity and promotes histone-3 and -4 protein acetylation. Treatment with MCP30 induces PTEN expression in a prostatic intraepithelial neoplasia (PIN) and PCa cell lines resulting in inhibition of Akt phosphorylation. In addition, MCP30 inhibits Wnt signaling activity through reduction of nuclear accumulation of beta-catenin and decreased levels of c-Myc and Cyclin-D1. Our data indicate that MCP30 selectively induces PIN and PCa apoptosis and inhibits HDAC-1 activity. These results suggest that Type I RIPs derived from plants are HDAC inhibitors that can be utilized in the prevention and treatment of prostate cancer.

[Physical and chemical characteristics of a new cefazolin sodium hydrate crystal].

One kind of new cefazolin sodium hydrate crystal was obtained in the isopropyl alcohol - water system. There are two symmetry independent molecules in the asymmetric unit, both being well ordered in the lattice, and ten independent water positions but generally four to six (mean five) water molecules and one sodium ion present in the unit cell structure. Huge solvent tunnels can be found. Again there are two general regions of water molecules, those in the large solvent tunnels and those in proximity of the sodium ion and the tetrazole moieties of the drug molecule. The physical and chemical characteristics of the new cefazolin sodium hydrate crystal are similar to that of the alpha-form cefazolin sodium crystal, and the new crystal has better chemical stability than amorphous cefazolin sodium powder.

Advances in rapid drug detection technology.

Spurious/Falsely-labeled/Falsified/Counterfeit (SFFC)drugs have become a major threat to public health, especially in rural areas of developing countries.The goal of this review is to provide an overview of rapid detection technologies for counterfeits recently reported, such as Near Infrared Spectroscopy, Near Infrared Chemical Imaging, Raman Spectroscopy, X-Ray Fluorescence, X-RayPowder Diffraction, Ion Mobility Spectrometry, Ion MobilityMass Spectrometry,Isotope Ratio Mass Spectrometry and visual analytical methods The advantages of each of these detection methods are introduced. Examples of characterization of SFFC drugs using the detection technology mentioned are presented. In addition, new characteristics and trends of SFFC drugs are listed and the solution is discussed.

The Outcomes of Minimally Invasive versus Open Posterior Approach Spinal Fusion in Treatment of Lumbar Spondylolisthesis: The Current Evidence from Prospective Comparative Studies.

Purpose. To investigate the evidence of minimally invasive (MI) versus open (OP) posterior lumbar fusion in treatment of lumbar spondylolisthesis from current prospective literatures. Methods. The electronic literature database of Pubmed, Embase, and Cochrane library was searched at April 2016. The data of operative time, estimated blood loss and length of hospital stay, visual analog scale (VAS) of both lower back pain and leg pain, Oswestry disability index (ODI), SF-36 PCS (physical component scores) and SF-36 MCS (mental component scores), complications, fusion rate, and secondary surgery were extracted and analyzed by STATA 12.0 software. Results. Five nonrandom prospective comparative studies were included in this meta-analysis. The meta-analysis showed that the MI group had a significantly longer operative time than OP group, less blood loss, and shorter hospital stay. No significant difference was found in back pain, leg pain, ODI, SF-36 PCS, SF-36 MCS, complications, fusion rate, and secondary surgery between MI and OP groups. Conclusion. The prospective evidence suggested that MI posterior fusion for spondylolisthesis had less EBL and hospital stay than OP fusion; however it took more operative time. Both MI and OP fusion had similar results in pain and functional outcomes, complication, fusion rate, and secondary surgery.

Epigenetic deregulated miR-375 contributes to the constitutive activation of JAK2/STAT signaling in myeloproliferative neoplasm.

Constitutive activation of Janus kinase 2/signal transducers and activators of transcription (JAK2/STAT) signaling caused by JAK2V617F and other mutations is central to the pathogenesis of myeloproliferative neoplasm (MPN). Negative regulators such as suppressors of cytokine signaling (SOCS) inhibit activated JAK2/STAT signaling. However, whether silencing of negative regulators facilitates JAK2/STAT signaling is unclear. Here, we report that loss of miR-375 expression contributes to the constitutive activation of JAK2/STAT signaling. MiR-375 reduced JAK2 protein level and repressed the activity of a luciferase reporter by binding 3'-untranslated regions, which was abolished by the mutation of the predicted miR-375-binding site. Meanwhile, a significant inverse correlation between the expressions of miR-375 and JAK2 was found in multiple types of leukemic cell lines and bone marrow mononuclear cells from MPN patients, suggesting that JAK2 may be a miR-375 target gene. Furthermore, forced expression of miR-375 inhibited constitutive and inducible JAK2/STAT signaling, suppressed cell proliferation, and decreased colony formation in hematopoietic progenitors from MPN patients. Finally, histone deacetylation (HDAC) inhibitors restored miR-375 expression, which was much lower in patients with MPN compared with healthy volunteers. Collectively, our data suggest that the loss of miR-375 expression enhances the constitutive and persistent activation of JAK2/STAT signaling. Restoration of miR-375 expression might contribute to the clinical treatment for MPN patients.

Analysis of differentially expressed lncRNAs in differentiation of bone marrow stem cells into neural cells.

Many studies have reported micro RNAs involved in the differentiation of bone marrow mesenchymal stem cells (BMSCs) into neural cells; however, the roles of long non-coding RNAs (lncRNAs) in the differentiation of BMSCs into neural cells remain poorly understood. We used microarray assays to compare the lncRNA and messenger RNA (mRNA) expression profiles in BMSCs and neural-induced BMSCs. We found a total of 24 lncRNAs and 738 mRNAs that were upregulated and 32 lncRNAs and 682 mRNAs that were downregulated in samples induced for 3h; 27 lncRNAs and 864 mRNAs that were upregulated and 37 lncRNAs and 968 mRNAs that were downregulated in 6h samples; and 23 lncRNAs and 1159 mRNAs that were upregulated or downregulated in both the 3h and 6h samples. For 23 differentially lncRNAs and 83 differentially mRNAs, 256 matched lncRNA-mRNA pairs were found. GO (Gene ontology) analysis showed that these lncRNAs were associated with biological processes, cellular components, and molecular functions. Twenty-five pathways were identified by pathway analysis. Then, RT-qPCR validation of the differentially expressed H19, Esco2, Pcdhb18, and RGD1560277 genes confirmed the microarray data. Our study revealed the expression patterns of lncRNAs in the differentiation of BMSCs into neural cells, and many lncRNAs were differentially expressed in induced BMSCs, suggesting that they may play key roles in processes of differentiation. Our findings may promote the use of BMSCs to treat neurodegenerative diseases and trauma.

Induced human bone marrow stromal cells differentiate into neural cells by bFGF and cocultured with olfactory ensheathing cells.

Bone marrow stromal cells (BMSCs) were considered as one of the strongest candidates for cell transplantations to treat neurological disorders. Previously, we had showed that BMSCs isolated from rats could be induced to differentiate into neural cells being cocultured with olfactory ensheathing cells (OECs). In this study, we further demonstrated the neural differentiation of human BMSCs (hBMSCs) when cocultured with OECs and daily supplement of bFGF (basic fibroblast growth factor). Transwell culture dishes with a 0.4-mm pore size were used to coculture hBMSCs and OECs. At different time points (12h, 24h, 3d, 7d, 14d), the induced hBMSCs were morphologically observed and performed immunocytofluorescence and quantitative RT-PCR (qRT-PCR). The number of neural markers-positive cells significantly increased after coculture, and gene expression of NSE, ß-III-tubulin, MAP2, GFAP also dramatically increased. Our study suggested that hBMSCs could be induced into neuron-like cells under conditions of coculture with OECs and daily supplement of bFGF. The differentiated autologous hBMSCs had a great potential for transplantation to treat CNS lesion.

In vitro neural differentiation of bone marrow stromal cells induced by cocultured olfactory ensheathing cells.

Bone marrow stromal cells (BMSCs) could be induced to differentiate into neural cells under certain conditions, nevertheless, optimal protocols that could be reproducible and reliable in generating transplantable BMSCs in vitro are still not available. We studied for the first time the neural differentiation of BMSCs induced by coculturing with olfactory ensheathing cells (OECs). BMSCs and OECs were isolated from bone marrow and nasal olfactory lamina propria of adult SD rats respectively, then brought to coculture with transwell culture dishes. At various time points (0h, 6h, 12h, 24h, 72h, 1 week and 2 weeks post-coculture), BMSCs were morphologically observed and processed for immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR). The number of cells assuming neural morphology dramatically increased at 1- and 2-week-post-coculture, so as the number of immunoreactive cells labeled by neural markers NSE, beta-III-tubulin, MAP2, GFAP and p75(NTR). Our findings demonstrate that BMSCs can efficiently differentiate into neural cells when coculturing with OECs, and the present protocol provides an alternative neurogenesis pathway for generating sufficient numbers of neural cells from BMSCs.