Differential metabolite analysis of the pharmacodynamic differences between different ratios of Dahuang ()-Taoren () herb pair.

OBJECTIVE: To explore the material basis of the difference of efficacy of Dahuang (Radix Et Rhizoma Rhei Palmati)-Taoren (Semen Persicae) (DT) drugs with different proportions. METHODS: Samples of different ratios of Dahuang (Radix et Rhizoma Rhei Palnati, DH) to Taoren (Semen Persicae, TR) (Group A 1:1, B 2:3, C 3:2) were analyzed based on gas chromatography time-of-flight mass spectrometry untargeted metabolomics technique. RESULTS: A total of 240 primary metabolites were detected. Forty-one differential metabolites involved nine differential metabolic pathways, of which four were closely related to the efficacy of DT in the treatment of heat and blood stasis syndrome. These pathways included the biosynthesis of amino acid (phenylalanine tyrosine and tryptophan), flavonoids, unsaturated fatty acids, and the glycolysis/glycogenesis pathway. CONCLUSION: There are significant differences in the efficacy of different ratios of DT drugs, and their optimal ratio for the treatment of heat and blood stasis syndrome should be 1:1.

In-vitro and in-vivo evaluation and anti-colitis activity of esculetin-loaded nanostructured lipid carrier decorated with DSPE-MPEG2000.

OBJECTIVE: Encapsulation of esculetin into DSPE-MPEG2000 carrier was performed to improve its water solubility and oral bioavailability, as well as enhance its anti-inflammatory effect on a mouse model of ulcerative colitis that was induced with dextran sulphate sodium (DSS). METHODS: We determined the in-vitro and in-vivo high-performance liquid chromatographic (HPLC) analysis method of esculetin; Esculetin-loaded nanostructure lipid carrier (Esc-NLC) was prepared using a thin-film dispersion method, wherein a particle size analyser was used to measure the particle size (PS) and zeta potential (ZP) of the Esc-NLC, while a transmission electron microscope (TEM) was employed to observe its morphology. Also, HPLC was used to measure its drug loading (DL), encapsulation efficiency (EE) and the in-vitro release of the preparation, as well as investigate the pharmacokinetic parameters. In addition, its anti-colitis effect was evaluated via histopathological examination of HE-stained sections and detection of the concentrations of tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1 beta (ß), and IL-6 in serum with ELISA kits. RESULTS: The PS of Esc-NLC was 102.29 ± 0.63 nm with relative standard deviation (RSD) of 1.08% (with poly-dispersity index-PDI of 0.197 ± 0.023), while the ZP was -15.67 ± 1.39 mV with RSD of 1.24%. Solubility of esculetin was improved coupled with prolonged release time. Its pharmacokinetic parameters were compared with that of free esculetin, wherein the maximum concentration of the drug in plasma was increased by 5.5 times. Of note, bioavailability of the drug was increased by 1.7 times, while the half-life was prolonged by 2.4 times. In the anti-colitis efficacy experiment, the mice in Esc and Esc-NLC groups exhibited significantly reduced levels of TNF-α, IL-1ß, and IL-6 in their sera comparable to the DSS group. Colon histopathological examination revealed that mice with ulcerative colitis in both Esc and Esc-NLC groups displayed improved inflammation, amid the Esc-NLC groups having the best prophylactic treatment effect. CONCLUSION: Esc-NLC could ameliorate DSS-induced ulcerative colitis by improving bioavailability, prolonging drug release time and regulating cytokine release. This observation confirmed the potential of Esc-NLC to reduce inflammation in ulcerative colitis, albeit the need for follow-up research to verify the application of this strategy to clinical treatment of ulcerative colitis.

Three-dimensional printed 316L stainless steel cardiovascular stent's electrolytic polishing and its mechanical properties / 生物医学工程学杂志

The interventional therapy of vascular stent implantation is a popular treatment method for cardiovascular stenosis and blockage. However, traditional stent manufacturing methods such as laser cutting are complex and cannot easily manufacture complex structures such as bifurcated stents, while three-dimensional (3D) printing technology provides a new method for manufacturing stents with complex structure and personalized designs. In this paper, a cardiovascular stent was designed, and printed using selective laser melting technology and 316L stainless steel powder of 0-10 µm size. Electrolytic polishing was performed to improve the surface quality of the printed vascular stent, and the expansion behavior of the polished stent was assessed by balloon inflation. The results showed that the newly designed cardiovascular stent could be manufactured by 3D printing technology. Electrolytic polishing removed the attached powder and reduced the surface roughness Ra from 1.36 µm to 0.82 µm. The axial shortening rate of the polished bracket was 4.23% when the outside diameter was expanded from 2.42 mm to 3.63 mm under the pressure of the balloon, and the radial rebound rate was 2.48% after unloading. The radial force of polished stent was 8.32 N. The 3D printed vascular stent can remove the surface powder through electrolytic polishing to improve the surface quality, and show good dilatation performance and radial support performance, which provides a reference for the practical application of 3D printed vascular stent.

The cGAS-STING signaling in cardiovascular and metabolic diseases: Future novel target option for pharmacotherapy

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS-STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns (mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS-STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism. Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS-STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases.

Local Log-Euclidean Multivariate Gaussian Descriptor and Its Application to Image Classification.

This paper presents a novel image descriptor to effectively characterize the local, high-order image statistics. Our work is inspired by the Diffusion Tensor Imaging and the structure tensor method (or covariance descriptor), and motivated by popular distribution-based descriptors such as SIFT and HoG. Our idea is to associate one pixel with a multivariate Gaussian distribution estimated in the neighborhood. The challenge lies in that the space of Gaussians is not a linear space but a Riemannian manifold. We show, for the first time to our knowledge, that the space of Gaussians can be equipped with a Lie group structure by defining a multiplication operation on this manifold, and that it is isomorphic to a subgroup of the upper triangular matrix group. Furthermore, we propose methods to embed this matrix group in the linear space, which enables us to handle Gaussians with Euclidean operations rather than complicated Riemannian operations. The resulting descriptor, called Local Log-Euclidean Multivariate Gaussian (L2EMG) descriptor, works well with low-dimensional and high-dimensional raw features. Moreover, our descriptor is a continuous function of features without quantization, which can model the first- and second-order statistics. Extensive experiments were conducted to evaluate thoroughly L2EMG, and the results showed that L2EMG is very competitive with state-of-the-art descriptors in image classification.

Tumor angiogenesis promoted by fusion of glioma stem/progenitor cells with bone marrow mesenchymal stem cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to clarify whether the fusion of bone marrow mesenchymal stem cells (MSCs) with tumor cells can promote tumor angiogensis.</p><p><b>METHODS</b>Human glioma stem/progenitor cells (GSPCs) (SU3 cells) were transfected with red fluorescent protein (RFP) gene. Bone marrow mesenchymal stem cells (MSCs) were harvested from nude mice with whole-body green fluorescent protein (GFP) gene expression. Then the two kinds of cells were co-cultured in vitro. At the same time SU3-RFP was transplanted into the brain of GFP-expressing nude mice to establish xenograft tumors. The co-cultured cells, GFP/RFP double positive (yellow) cells and blood vessels obtained from the xenograft tumors were observed under fluorescent microscope and laser scanning confocal microscope.</p><p><b>RESULTS</b>After five passages in vitro, MSCs maintained the proliferative activity and highly expressed CD105. CD105 was also expressed in the femurs of GFP-expressing nude mice, tumor cells, blood vessels of SU3 xenograft tumors, and clinical malignant gliomas. When MSCs were co-cultured with SU3-RFP, the ratio of yellow cells co-expressing RFP and GFP was significantly increased after extended time and continuous passages. According to the flow cytometry, yellow cells co-expressing RFP and GFP were 83.7% of the cultured cells. In tissue slices of the xenograft tumors, bundles of yellow vessel-like structure and cross-sectioned yellow vascular wall structures including vascular wall stroma cells were observed with RFP and GFP expression, and were identified as de novo formed vessels derived from fusion of MSCs with SU3-RFP cells.</p><p><b>CONCLUSION</b>Cell fusion occurs between tumor cells and host MSCs and it promotes tumor angiogenesis.</p>

Establishment of a new congenic inbred mouse strain named Foxn1nu.B6-CAG-EGFP/SU / 中国比较医学杂志

Objective To establish a new congenic inbred mouse strain carrying and expressing EGFP and Foxn1nugene for cancer research including human glioma as well .Methods According to criterion of GB14923-2010, the male Foxn1nu nude mice backcross the female C57BL/6-Tg (CAG-EGFP) transgenic mice for 10 times, Then identify the phenotype using the methods and equipment as below: fluorescent flashlight and matching glasses; multifunction vivo imager; fluorescence microscopy.Results The congenic inbred mouse strain named Foxn1nu.B6-CAG-EGFP/SU ( Soochow University ) .All the 14 biochemical loci are homozygous and same with Balb/c mouse in addition to the Pep3 loci (“b” type instead of “a” type).Peripheral blood lymphocyte count shows the lymphocytes occupy 15%of nucleated cells;T lymphocytes occupy 0.3%, meet the requirement of inbred strain of EGFP nude mice .Conclusions Established a new congenic inbred strain -Foxn1nu.B6-CAG-EGFP/SU which both express EGFP stably, and own immunodeficiency with lack of T lymphocytes .The phenotype “b” of biochemical loci “Pep3” is the unique characteristic that distinguish SU to Foxn1nu.

Clinical significance of BP1 gene expression in human thyroid cancer / 中华内分泌外科杂志

Objective To detect the expression of BP1 gene in thyroid cancer and its relationship with clinicopathological features of thyroid cancer.Methods BP1 gene expression in 60 cases of thyroid cancer tissues and 20 cases of normal thyroid tissues were detected by in situ hybridization and immunohistochemistry.Results The positive expression rate of BP1 mRNA was 78.3 ％ (47/60) in the 60 cases of thyroid cancer tissues while it was 20％ (4/20) in the 20 cases of normal thyroid tissues detected by in situ hybridization.The difference had statistical significance (P ＜ 0.05).Of the 3 pathological types of thyroid cancer,the positive expression rate of papillary carcinoma was 81.6％ (40/49),follicular carcinoma 85.7％ (6/7),and medullary carcinoma 25.0％ (1/4).The expression of BP1 mRNA had statistical difference between medullary carcinoma and other pathological types like papillary carcinoma and follicular carcinoma (P ＜ 0.05).The positive expression rate of BP1 protein was 93.3％ (56/60)in the 60 cases of thyroid cancer tissues while it was 10.0％ (2/20) in the 20 cases of normal thyroid tissues detected by immunohistochemistry.The difference had statistical significance(P ＜0.05).Conclusion BP1 gene expression is up-regulated in human thyroid cancer and it is related to tumor stage and pathological type but not related to patients' age,sex or lymph node metastasis.

BPD surgery on type 2 diabetes mellitus in GK rats / 中华内分泌外科杂志

Objective To investigate the therapeutic effects and mechanism of biliopancreatic diversion (BPD) surgery on type 2 diabetes mellitus(T2DM) in GK rats.Methods 16 GK rats were randomly divided into 2 groups:BPD surgery group included 10 rats undergoing BPD surgery,sham-BPD group included 6 rats undergoing a sham operation.Fasting plasma glucose,insulin,glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide(GIP)were detected one week before BPD surgery and the 1st week,4th week,10th week,26th week after BPD surgery.Oral glucose tolerance test(OGTT) and insulin tolerance test(ITT) were done in the 10th week after BPD surgery.Results There was no statistical difference in fasting plasma glucose,insulin,plasma GLP-1 or GIP between the 2 groups before surgery.Plasma glucose had significant reduction in BPD group compared to that in the sham group(P ＜0.05) and insulin level had no significant difference between the 2 groups.Rats in BPD group had significant improvement in glucose tolerance and insulin sensitivity compared to those in the sham group.Serum level of GLP-1 was significantly elevated in BPD group compared to that before surgery (P =0.0337 at the 1st week after surgery; P =0.0002 at the 4th week after surgery,P ＜ 0.0001 at the 10th week after surgery,P ＜0.0001 at the 26th week after surgery) and that in sham-BPD group(P =0.0354 at the 1st week after surgery,P =0.0032 at the 4th week after surgery,P =0.0001 at the 10th week after surgery,P ＜0.0001 at the 26th week).Serum level of GIP was significantly lowered in BPD group compared to that before surgery(P =0.0189 at the 1st week after surgery; P =0.0007 at the 4th week after surgery,P =0.0003 at the 10th week after surgery,P ＜0.0001 at the 26th week after surgery) and that in sham-BPD group(P =0.0089 at the 1st week after surgery,P =0.0002 at the 4th week after surgery,P =0.0006 at the 10th week after surgery,P ＜0.0001 at the 26th week after surgery).The difference had statistical significance (P ＜0.05).Conclusion BPD surgery can significantly reduce fasting plasma glucose,improve glucose tolerance and insulin sensitivity.The change of serum levels of GLP-1 and GIP may play the major role in BPD treatment of diabetes mellitus.

Acetoxybenzhydrols as highly active and stable analogues of 1'S-1'-acetoxychavicol, a potent antiallergic principal from Alpinia galanga.

Through SAR studies on 1'S-1'-acetoxychavicol acetate (1) against Type I antiallergic activity by indexing release of beta-hexosaminidase, a marker of antigen-IgE-mediated degranulation in RBL-2H3 cells, more stable and potent analogue, 4-(methoxycarbonyloxyphenylmethyl)phenyl acetate (16), has been developed. The compound 16 also strongly inhibited the antigen-IgE-mediated TNF-alpha and IL-4 production.