Applications of New Technologies and New Methods in ZHENG Differentiation

With the hope to provide an effective approach for personalized diagnosis and treatment clinically, Traditional Chinese Medicine (TCM) is being paid increasing attention as a complementary and alternative medicine. It performs treatment based on ZHENG (TCM syndrome) differentiation, which could be identified as clinical special phenotypes by symptoms and signs of patients. However, it caused skepticism and criticism because ZHENG classification only depends on observation, knowledge, and clinical experience of TCM practitioners, which is lack of objectivity and repeatability. Scientists have done fruitful researches for its objectivity and standardization. Compared with traditional four diagnostic methods (looking, listening and smelling, asking, and touching), in this paper, the applications of new technologies and new methods on the ZHENG differentiation were systemically reviewed, including acquisition, analysis, and integration of clinical data or information. Furthermore, the characteristics and application range of these technologies and methods were summarized. It will provide reference for further researches

Periostin: a promising target of therapeutical intervention for prostate cancer

<p>Abstract</p> <p>Background</p> <p>In our recent study, Periostin was up-regulated in prostate cancer(PCa) compared with benign prostate hyperplasia (BPH) by proteomics analysis of prostate biopsies. We investigated the effect of sliencing Periostin by RNA interference (RNAi) on the proliferation and migration of PCa LNCap cell line.</p> <p>Methods</p> <p>All the prostate biopsies from PCa, BPH and BPH with local prostatic intraepithelial neoplasm(PIN) were analyzed by iTRAQ(Isobaric tags for relative and absolute quantification) technology. Western blotting and immunohistochemical staining were used to verify Periostin expression in the tissues of PCa. Periostin expression in different PCa cell lines was determined by immunofluorescence staining, western blotting and reverse transcription PCR(RT-PCR). The LNCap cells with Periostin expression were used for transfecting shRNA-Periostin lentiviral particles. The efficancy of transfecting shRNA lentiviral particles was evaluated by immunofluorescence, western blotting and Real-time PCR. The effect of silencing Periostin expression by RNAi on proliferation of LNCap cells was determined by MTT assay and tumor xenografts. The tissue slices from theses xenografts were analyzed by hematoxylin and eosin(HE) staining. The expression of Periostin in the xenografts was deteminned by Immunohistochemical staining and western blotting. The migration of LNCap cells after silencing Periostin gene expression were analyzed in vitro.</p> <p>Results</p> <p>Periostin as the protein of interest was shown 9.12 fold up-regulation in PCa compared with BPH. The overexpression of Periostin in the stroma of PCa was confirmed by western blotting and immunohistochemical staining. Periostin was only expressed in PCa LNCap cell line. Our results indicated that the transfection ratio was more than 90%. As was expected, both the protein level and mRNA level of Periostin in the stably expressing shRNA-Periostin LNCap cells were significantly reduced. The stably expressing shRNA-Periostin LNCap cells growed slowly in vitro and in vivo. The tissues of xenografts as PCa were verificated by HE staining. Additionally, the weak positive Periostin expressed tumor cells could be seen in the tissues of 6 xenografts from the group of down-regulated Periostin LNCap cells which had a significant decrease of the amount of Periostin compared to the other two group. Furthermore, our results demonstrated that sliencing Periostin could inhibit migration of LNCap cells in vitro.</p> <p>Conclusions</p> <p>Our data indicates that Periostin as an up-regulated protein in PCa may be a promising target of therapeutical intervention for PCa in future.</p

Development and biodistribution of trans-resveratrol loaded chitosan nanoparticles with free amino groups

The conventional method for preparing chitosan nanoparticles (CS-NPs) leads to the surface amino groups protonated and unable to link other useful moieties. In this study, we optimized the method of sodium chloride precipitation our lab established before to produce CS-NPs with surface free amino groups. The effects of preparation conditions on the size and encapsulation efficiency were examined. As surface amino groups may exert special effect on the NPs biodistribution, in vivo distribution was investigated after intravenous administration to the mice. The optimized CS-NPs were round with the mean diameter of 257 ± 21 nm. Compared with trans-resveratrol solution, the CS-NPs had longer circulation time in vivo. The AUC of CS-NPs in liver was 2.29 fold AUC of the solution. This study demonstrates that not only can the unique CS-NPs be modified to obtain active targeting systems, they are also an excellent candidate for liver targeting treatment.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Qushi Huayu decoction ameliorates non-alcoholic fatty liver disease in rats by modulating gut microbiota and serum lipids

IntroductionNon-alcoholic fatty liver disease (NAFLD) is a multifactorial disease. As a clinical empirical prescription of traditional Chinese medicine, Qushi Huayu decoction (QHD) has attracted considerable attention for its advantages in multi-target treatment of NAFLD. However, the intervention mechanism of QHD on abnormal lipid levels and gut microbiota in NAFLD has not been reported.MethodsTherefore, we verified the therapeutic effect of QHD on high-fat diet (HFD)-induced NAFLD in rats by physiological parameters and histopathological examination. In addition, studies on gut microbiota and serum lipidomics based on 16S rRNA sequencing and ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) were conducted to elucidate the therapeutic mechanism of NAFLD in QHD.ResultsThe changes in gut microbiota in NAFLD rats are mainly reflected in their diversity and composition, while QHD treated rats restored these changes. The genera Blautia, Lactobacillus, Allobaculum, Lachnoclostridium and Bacteroides were predominant in the NAFLD group, whereas, Turicibacter, Blautia, Sporosarcina, Romboutsia, Clostridium_sensu_stricto_1, Allobaculum, and Psychrobacter were predominant in the NAFLD+QHD group. Lipid subclasses, including diacylglycerol (DG), triglycerides (TG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidic acid (PA), phosphatidylserine (PS), lysophosphatidylinositol (LPI), and phosphatidylglycerol (PG), were significantly different between the NAFLD and the control groups, while QHD treatment significantly altered the levels of DG, TG, PA, lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), and platelet activating factor (PAF). Finally, Spearman’s correlation analysis showed that NAFLD related differential lipid molecules were mainly associated with the genera of Bacteroides, Blautia, Lachnoclostridium, Clostridium_sensu_stricto_1, and Turicibacter, which were also significantly correlated with the biological parameters of NAFLD.DiscussionTaken together, QHD may exert beneficial effects by regulating the gut microbiota and thus intervening in serum lipids

Correction: Inhibitor SBFI26 suppresses the malignant progression of castration-resistant PC3-M cells by competitively binding to oncogenic FABP5.

[This corrects the article DOI: 10.18632/oncotarget.16055.]

Multifractal Analysis of Pore Structure and Evaluation of Deep-Buried Cambrian Dolomite Reservoir with Image Processing: A Case from Tarim Basin, NW China

Reservoir pore space assessment is of great significance for petroleum exploration and production. However, it is difficult to describe the pore characteristics of deep-buried dolomite reservoirs with the traditional linear method because these rocks have undergone strong modification by tectonic activity and diagenesis and show significant pore space heterogeneity. In this study, 38 dolostone samples from 4 Cambrian formations of Tarim Basin in NW China were collected and 135 thin section images were analyzed. Multifractal theory was used for evaluation of pore space heterogeneity in deep-buried dolostone based on thin section image analysis. The physical parameters, pore structure parameters, and multifractal characteristic parameters were obtained from the digital images. Then, the relationships between lithology and these parameters were discussed. In addition, the pore structure was classified into four categories using K-means clustering analysis based on multifractal parameters. The results show that the multifractal phenomenon generally exists in the pore space of deep-buried dolomite and that multifractal analysis can be used to characterize the heterogeneity of pore space in deep-buried dolomite. For these samples, multifractal parameters, such as αmin, αmax, ΔαL, ΔαR, Δf, and AI, correlate strongly with porosity but only slightly with permeability. However, the parameter Δα, which is usually used to reveal heterogeneity, does not show an obvious link with petrophysical properties. Of dolomites with different fabrics, fine crystalline dolomite and medium crystalline dolomite show the best petrophysical properties and show significant differences in multifractal parameters compared to other dolomites. More accurate porosity estimations were obtained with the multifractal generalized fractal dimension, which provides a new method for porosity prediction. The various categories derived from the K-means clustering analysis of multifractal parameters show distinct differences in petrophysical properties. This proves that reservoir evaluation and pore structure classification can be accurately performed with the K-means clustering analysis method based on multifractal parameters of pore space in deep-buried dolomite reservoirs

Therapeutic effect of Sanhua decoction on rats with middle cerebral artery occlusion and the associated changes in gut microbiota and short-chain fatty acids.

Sanhua decoction (SHD), a traditional prescription, has long been used in treating ischemic stroke (IS). However, the therapeutic effect of SHD and the associated changes in gut microbiota and short-chain fatty acids (SCFAs) are uncertain. In this study, a rat model of IS was established by the middle cerebral artery occlusion (MCAO). By evaluating the cerebral infarct area and brain tissue pathology, it was found that SHD ameliorated IS-related symptoms in MCAO rats. Using 16S rRNA gene sequencing, we found that SHD reduced abnormally elevated Lactobacillus and opportunistic pathogens such as Desulfovibrio, but increased some beneficial bacteria that produce SCFAs, including Clostridia, Lachnospiraceae, Ruminococcaceae, and Coprococcus. KEGG analysis revealed that SHD regulates several pathways, including D-arginine and D-ornithine metabolism, polyketide sugar unit biosynthesis, and cyanoamino acid metabolism, which are significantly altered in MCAO rats. By gas chromatography-mass spectrometry detection of SCFAs, we found that fecal acetic acid, valeric acid, and caproic acid were significantly increased in MCAO rats, whereas propionic acid and isobutyric acid were decreased. SHD reversed the changes in acetic acid and propionic acid in the model rats and significantly increased fecal butyric acid. In addition, MCAO rats had significantly higher serum levels of acetic acid, butyric acid, isovaleric acid, and valeric acid, and lower levels of caproic acid. Altered serum levels of butyric acid, isovaleric acid, valeric acid, and caproic acid were restored, and the level of isobutyric acid was reduced after SHD administration. Spearman analysis revealed that cerebral infarct area had a strong correlation with Bifidobacterium, Desulfovibrio, Lachnospiraceae, Lactobacillus, acetic acid, valeric acid, and caproic acid. Overall, this study demonstrates for the first time that the effect of SHD on IS may be related to gut microbiota and SCFAs, providing a potential scientific explanation for the ameliorative effect of SHD on IS

3D-QSAR, Molecular Docking and Molecular Dynamics Simulation of Pseudomonas aeruginosa LpxC Inhibitors

As an important target for the development of novel antibiotics, UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) has been widely studied. Pyridone methylsulfone hydroxamate (PMH) compounds can effectively inhibit the catalytic activity of LpxC. In this work, the three-dimensional quantitative structure-activity relationships of PMH inhibitors were explored and models with good predictive ability were established using comparative molecular field analysis and comparative molecular similarity index analysis methods. The effect of PMH inhibitors’ electrostatic potential on the inhibitory ability of Pseudomonas aeruginosa LpxC (PaLpxC) is revealed at the molecular level via molecular electrostatic potential analyses. Then, two molecular dynamics simulations for the PaLpxC and PaLpxC-inhibitor systems were also performed respectively to investigate the key residues of PaLpxC hydrolase binding to water molecules. The results indicate that orderly alternative water molecules can form stable hydrogen bonds with M62, E77, T190, and H264 in the catalytic center, and tetracoordinate to zinc ion along with H78, H237, and D241. It was found that the conformational transition space of PaLpxC changes after association with PMH inhibitors through free energy landscape and cluster analyses. Finally, a possible inhibitory mechanism of PMH inhibitors was proposed, based on our molecular simulation. This paper will provide a theoretical basis for the molecular design of LpxC-targeting antibiotics

Periostin Mediates TGF-β-Induced Epithelial Mesenchymal Transition in Prostate Cancer Cells

Background: In our previous study, we found that periostin was upregulated in prostate cancer, and its expression could be modulated by TGF-β. TGF-β could upregulate periostin expression in some cells, and both TGF-β and periostin could induce epithelial mesenchymal transition (EMT). We aimed to study the effect of periostin in the process of TGF-β-induced EMT in prostate cancer cells. Methods: We constructed a lentivirus vector containing the periostin gene and transduced it into PC3 and DU145 cells. After confirming periostin overexpression by PCR and Western blotting, we used an MTT assay to establish a growth curve to measure cell proliferation. Additionally, we performed transwell and wound healing assays to measure cell invasion and migration, respectively. Lastly, we measured the expression of EMT associated factors using Western blot analysis to test the effect of periostin on EMT in prostate cancer cells. Results: PCR and Western blot analyses confirmed that periostin was upregulated after infection with the periostin lentiviral vector. Periostin overexpression promoted increased cell proliferation, invasion, and migration as measured by MTT, transwell, and wound healing assays, respectively. Western blot analysis illustrated that periostin overexpression increased the expression of EMT associated factors, and periostin overexpression activated Akt and GSK-3β, which could be inhibited using a PI3K inhibitor. Additionally, TGF-β increased the levels of STAT3, Twist1 and periostin, while both STAT3 shRNA and Twist1 shRNA inhibited periostin expression. However, STAT3 shRNA also decreased Twist1 expression. Although reduction of STAT3, Twist1 or periostin levels with shRNA inhibited TGF-β-induced overexpression of EMT associated factors, periostin overexpression could reverse such inhibition by interfering with STAT3 and Twist1. Similarly, periostin overexpression also reversed inhibition of cell invasion induced by interference of STAT3 and Twist1. Conclusion: Our findings indicate that periostin is an important mediator of TGF-β-induced EMT and suggest that periostin is a potential therapeutic target for suppressing the metastatic progression of prostate cancer